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Sample records for inhibit sodium antimony

  1. Leishmania donovani Isolates with Antimony-Resistant but Not -Sensitive Phenotype Inhibit Sodium Antimony Gluconate-Induced Dendritic Cell Activation

    PubMed Central

    Singhal, Eshu; Bisht, Kamlesh Kumar; Singh, Alpana; Bhaumik, Suniti; Basu, Rajatava; Sen, Pradip; Roy, Syamal

    2010-01-01

    The inability of sodium antimony gluconate (SAG)-unresponsive kala-azar patients to clear Leishmania donovani (LD) infection despite SAG therapy is partly due to an ill-defined immune-dysfunction. Since dendritic cells (DCs) typically initiate anti-leishmanial immunity, a role for DCs in aberrant LD clearance was investigated. Accordingly, regulation of SAG-induced activation of murine DCs following infection with LD isolates exhibiting two distinct phenotypes such as antimony-resistant (SbRLD) and antimony-sensitive (SbSLD) was compared in vitro. Unlike SbSLD, infection of DCs with SbRLD induced more IL-10 production and inhibited SAG-induced secretion of proinflammatory cytokines, up-regulation of co-stimulatory molecules and leishmanicidal effects. SbRLD inhibited these effects of SAG by blocking activation of PI3K/AKT and NF-κB pathways. In contrast, SbSLD failed to block activation of SAG (20 µg/ml)-induced PI3K/AKT pathway; which continued to stimulate NF-κB signaling, induce leishmanicidal effects and promote DC activation. Notably, prolonged incubation of DCs with SbSLD also inhibited SAG (20 µg/ml)-induced activation of PI3K/AKT and NF-κB pathways and leishmanicidal effects, which was restored by increasing the dose of SAG to 40 µg/ml. In contrast, SbRLD inhibited these SAG-induced events regardless of duration of DC exposure to SbRLD or dose of SAG. Interestingly, the inhibitory effects of isogenic SbSLD expressing ATP-binding cassette (ABC) transporter MRPA on SAG-induced leishmanicidal effects mimicked that of SbRLD to some extent, although antimony resistance in clinical LD isolates is known to be multifactorial. Furthermore, NF-κB was found to transcriptionally regulate expression of murine γglutamylcysteine synthetase heavy-chain (mγGCShc) gene, presumably an important regulator of antimony resistance. Importantly, SbRLD but not SbSLD blocked SAG-induced mγGCS expression in DCs by preventing NF-κB binding to the mγGCShc promoter. Our

  2. Inhibition of ABC Transporters Abolishes Antimony Resistance in Leishmania Infection▿

    PubMed Central

    Mookerjee Basu, Jayati; Mookerjee, Ananda; Banerjee, Rajdeep; Saha, Manik; Singh, Subhankar; Naskar, Ksudiram; Tripathy, Gayetri; Sinha, Prabhat K.; Pandey, Krishna; Sundar, Shyam; Bimal, Sanjeev; Das, Pradip K.; Choudhuri, Soumitra K.; Roy, Syamal

    2008-01-01

    The emergence of antimony (Sb) resistance has jeopardized the treatment of visceral leishmaniasis in various countries. Previous studies have considered the part played by leishmanial parasites in antimony resistance, but the involvement of host factors in the clinical scenario remained to be investigated. Here we show that unlike infection with Sb-sensitive (Sbs) Leishmania donovani, infection with Sb-resistant (Sbr) L. donovani induces the upregulation of multidrug resistance-associated protein 1 (MRP1) and permeability glycoprotein (P-gp) in host cells, resulting in a nonaccumulation of intracellular Sb following treatment with sodium antimony gluconate (SAG) favoring parasite replication. The inhibition of MRP1 and P-gp with resistance-modifying agents such as lovastatin allows Sb accumulation and parasite killing within macrophages and offers protection in an animal model in which infection with Sbr L. donovani is otherwise lethal. The occurrence of a similar scenario in clinical cases is supported by the findings that unlike monocytes from SAG-sensitive kala-azar (KA) patients, monocytes from SAG-unresponsive KA patients overexpress P-gp and MRP1 and fail to accumulate Sb following in vitro SAG treatment unless pretreated with inhibitors of ABC transporters. Thus, the expression status of MRP1 and P-gp in blood monocytes may be used as a diagnostic marker for Sb resistance and the treatment strategy can be designed accordingly. Our results also indicate that lovastatin, which can inhibit both P-gp and MRP1, might be beneficial for reverting Sb resistance in leishmaniasis as well as drug resistance in other clinical situations, including cancer. PMID:18056276

  3. Antimony

    Integrated Risk Information System (IRIS)

    Antimony ; CASRN 7440 - 36 - 0 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effects

  4. Antimony tartrate corrosion inhibitive composition for coolant systems

    SciTech Connect

    Payerle, N.E.

    1987-08-11

    An automobile coolant concentrate is described comprising (a) a liquid polyhydric alcohol chosen from the group consisting of ethylene glycol, propylene glycol, diethylene glycol and mixtures thereof, and (b) corrosion inhibitors in a corrosion inhibitory amount with respect to corrosion of lead-containing solders, the corrosion inhibitors comprising (i) an alkali metal antimony tartrate, and (ii) an azole compound.

  5. Meglumine antimoniate is more effective than sodium stibogluconate in the treatment of cutaneous leishmaniasis.

    PubMed

    Yesilova, Yavuz; Surucu, Hacer Altın; Ardic, Nurittin; Aksoy, Mustafa; Yesilova, Abdullah; Oghumu, Steve; Satoskar, Abhay R

    2016-01-01

    Sodium stibogluconate (SSG, Pentostam) and meglumine antimoniate (MA, Glucantime) are two antimonials that are widely used to treat cutaneous leishmaniasis (CL), but the relative efficacies of these treatments are not clear. The aim of this study is to compare the efficacy of intralesional SSG with intralesional MA therapy in the treatment of CL. One month after completion of the therapy, 1431 of 1728 patients (82%) who received intralesional MA showed complete clinical cure compared to 1157 of 1728 patients (67%) in the SSG group. Patients who did not respond to the first round of therapy were re-administered the same treatment but with twice weekly injections. Following completion of the second course of therapy, 237 of 297 patients (80%) in the MA group and 407 of 561 patients (72%) in the SSG group healed their lesions by 1-month post-treatment. At both times, the differences in cure rates between MA and SSG groups were statistically significant (p < 0.05). Cure rates in the MA group were always significantly higher than SSG groups irrespective of other parameters including age, gender, lesion site and type of lesion. Intralesional MA is more effective than intralesional SSG in the treatment of CL.

  6. Antimony nanoparticles anchored in three-dimensional carbon network as promising sodium-ion battery anode

    NASA Astrophysics Data System (ADS)

    Luo, Wen; Zhang, Pengfei; Wang, Xuanpeng; Li, Qidong; Dong, Yifan; Hua, Jingchen; Zhou, Liang; Mai, Liqiang

    2016-02-01

    A novel composite with antimony (Sb) nanoparticles anchored in three-dimensional carbon network (denoted as SbNPs@3D-C) is successfully synthesized via a NaCl template-assisted self-assembly strategy, followed by freeze-drying and one-step in-situ carbonization. The three-dimensional interconnected macroporous carbon framework can not only stabilize the architecture and buffer the volume expansion for Sb nanoparticles, but also provide high electrical conductivity for the whole electrode. Consequently, as a sodium-ion battery anode, the SbNPs@3D-C delivers a high reversible capacity (456 mAh g-1 at 100 mA g-1), stable cycling performance (94.3% capacity retention after 500 cycles at 100 mA g-1) as well as superior rate capability (270 mAh g-1 at 2000 mA g-1). When compared with commercial Sb particles, the SbNPs@3D-C exhibits dramatically enhanced electrochemical performance. Free from expensive template sources and complex manipulation, this work might shed some light on the synthesis of low-cost and high-performance materials for the next "beyond lithium" battery generation.

  7. Reduced Graphene Oxide/Tin-Antimony Nanocomposites as Anode Materials for Advanced Sodium-Ion Batteries.

    PubMed

    Ji, Liwen; Zhou, Weidong; Chabot, Victor; Yu, Aiping; Xiao, Xingcheng

    2015-11-11

    Reduced graphene oxides loaded with tin-antimony alloy (RGO-SnSb) nanocomposites were synthesized through a hydrothermal reaction and the subsequent thermal reduction treatments. Transmission electron microscope images confirm that SnSb nanoparticles with an average size of about 20-30 nm are uniformly dispersed on the RGO surfaces. When they were used as anodes for rechargeable sodium (Na)-ion batteries, these as-synthesized RGO-SnSb nanocomposite anodes delivered a high initial reversible capacity of 407 mAh g(-1), stable cyclic retention for more than 80 cycles and excellent cycle stability at ultra high charge/discharge rates up to 30C. The significantly improved performance of the synthesized RGO-SnSb nanocomposites as Na-ion battery anodes can be attributed to the synergetic effects of RGO-based flexible framework and the nanoscale dimension of the SnSb alloy particles (<30 nm). Nanosized intermetallic SnSb compounds can exhibit improved structural stability and conductivity during charge and discharge reactions compared to the corresponding individuals (Sn and Sb particles). In the meantime, RGO sheets can tightly anchor SnSb alloy particles on the surfaces, which can not only effectively suppress the agglomeration of SnSb particles but also maintain excellent electronic conduction. Furthermore, the mechanical flexibility of the RGO phase can accommodate the volume expansion and contraction of SnSb particles during the prolonged cycling, therefore, improve the electrode integrity mechanically and electronically. All of these contribute to the electrochemical performance improvements of the RGO-SnSb nanocomposite-based electrodes in rechargeable Na-ion batteries.

  8. Co-administration of glycyrrhizic acid with the antileishmanial drug sodium antimony gluconate (SAG) cures SAG-resistant visceral leishmaniasis.

    PubMed

    Bhattacharjee, Amrita; Majumder, Saikat; Majumdar, Suchandra Bhattacharyya; Choudhuri, Soumitra Kumar; Roy, Syamal; Majumdar, Subrata

    2015-03-01

    Since there are very few affordable antileishmanial drugs available, antimonial resistance has crippled antileishmanial therapy, thereby emphasising the need for development of novel therapeutic strategies. This study aimed to evaluate the antileishmanial role of combined therapy with sodium antimony gluconate (SAG) and the triterpenoid glycyrrhizic acid (GA) against infection with SAG-resistant Leishmania (GE1F8R). Combination therapy with GA and SAG successfully limited infection with SAG-resistant Leishmania in a synergistic manner (fractional inhibitory concentration index <1.0). At the same time, mice infected with SAG-resistant Leishmania and co-treated with GA and SAG exhibited a significant reduction in hepatic and splenic parasite burden. In probing the mechanism, it was observed that GA treatment suppressed the expression and efflux activity of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), two host ABC transporters responsible for antimony efflux from host cells infected with SAG-resistant parasites. This suppression correlated with greater intracellular antimony retention during SAG therapy both in vitro and in vivo, which was reflected in the reduced parasite load. Furthermore, co-administration of GA and SAG induced a shift in the cytokine balance towards a Th1 phenotype by augmenting pro-inflammatory cytokines (such as IL-12, IFNγ and TNFα) and inducing nitric oxide generation in GE1F8R-infected macrophages as well as GE1F8R-infected mice. This study aims to provide an affordable leishmanicidal alternative to expensive antileishmanial drugs such as miltefosine and amphotericin B. Furthermore, this report explores the role of GA as a resistance modulator in MRP1- and P-gp-overexpressing conditions. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  9. Chemical bonding between antimony and ionic liquid-derived nitrogen-doped carbon for sodium-ion battery anode

    NASA Astrophysics Data System (ADS)

    Xu, Xin; Si, Ling; Zhou, Xiaosi; Tu, Fengzhang; Zhu, Xiaoshu; Bao, Jianchun

    2017-05-01

    Antimony has received a great deal of attention as a promising anode material for sodium-ion batteries (SIBs) due to its high theoretical capacity of 660 mAh g-1. However, this application is significantly hampered by inherent large volume change and sluggish kinetics. To address these issues, an antimony-cyano-based ionic liquid-derived nitrogen-doped carbon (Sbsbnd CNC) hybrid is proposed and synthesized by ball-milling and subsequent pyrolysis treatment. As an anode material for SIBs, the as-synthesized Sbsbnd CNC hybrid delivers reversible capacities of 475 mAh g-1 at a current density of 100 mA g-1 and 203 mAh g-1 at 5000 mA g-1, and a 92.4% capacity retention based on the first-cycle capacity after 150 cycles at 100 mA g-1. Using ex situ X-ray photoelectron spectroscopy and elemental mapping techniques, we attribute the good structural integrity to the formation of Sbsbnd Nsbnd C bonds between Sb and the cyano-based ionic liquid-derived N-doped carbon matrix. Moreover, the presence of N-doped carbon network in the hybrid material serves as a robust protective cover and an electrical highway, buffering the substantial volume expansion of Sb nanoparticles and ensuring the fast electron transport for stable cycling operation.

  10. High-capacity antimony sulphide nanoparticle-decorated graphene composite as anode for sodium-ion batteries.

    PubMed

    Yu, Denis Y W; Prikhodchenko, Petr V; Mason, Chad W; Batabyal, Sudip K; Gun, Jenny; Sladkevich, Sergey; Medvedev, Alexander G; Lev, Ovadia

    2013-01-01

    Sodium-ion batteries are an alternative to lithium-ion batteries for large-scale applications. However, low capacity and poor rate capability of existing anodes are the main bottlenecks to future developments. Here we report a uniform coating of antimony sulphide (stibnite) on graphene, fabricated by a solution-based synthesis technique, as the anode material for sodium-ion batteries. It gives a high capacity of 730 mAh g(-1) at 50 mA g(-1), an excellent rate capability up to 6C and a good cycle performance. The promising performance is attributed to fast sodium ion diffusion from the small nanoparticles, and good electrical transport from the intimate contact between the active material and graphene, which also provides a template for anchoring the nanoparticles. We also demonstrate a battery with the stibnite-graphene composite that is free from sodium metal, having energy density up to 80 Wh kg(-1). The energy density could exceed that of some lithium-ion batteries with further optimization.

  11. Sodium Channel Inhibiting Marine Toxins

    NASA Astrophysics Data System (ADS)

    Llewellyn, Lyndon E.

    Saxitoxin (STX), tetrodotoxin (TTX) and their many chemical relatives are part of our daily lives. From killing people who eat seafood containing these toxins, to being valuable research tools unveiling the invisible structures of their pharmacological receptor, their global impact is beyond measure. The pharmacological receptor for these toxins is the voltage-gated sodium channel which transports Na ions between the exterior to the interior of cells. The two structurally divergent families of STX and TTX analogues bind at the same location on these Na channels to stop the flow of ions. This can affect nerves, muscles and biological senses of most animals. It is through these and other toxins that we have developed much of our fundamental understanding of the Na channel and its part in generating action potentials in excitable cells.

  12. Inhaled sodium metabisulphite induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate.

    PubMed Central

    Dixon, C M; Ind, P W

    1990-01-01

    1. The effects of nedocromil sodium and sodium cromoglycate on bronchoconstriction induced by inhaled sodium metabisulphite have been studied in eight atopic subjects, three of whom had mild asthma. 2. Nedocromil sodium (4 mg, 7.8 X 10(-6) M), sodium cromoglycate (10 mg, 24.1 X 10(-6) M) and matched placebo were administered by identical metered dose inhalers 30 min before a dose-response to sodium metabisulphite (5-100 mg ml-1) was performed. 3. Maximum fall in sGaw after placebo pre-treatment was -43.9 +/- 3.3% baseline (mean +/- s.e. mean). At the same metabisulphite concentration maximum fall in sGaw after sodium cromoglycate was -13.0 +/- 3.6% and after nedocromil sodium was +4.3 +/- 6.8%. Nedocromil sodium prevented any significant fall in sGaw even after higher concentrations of metabisulphite. 4. Both nedocromil sodium, 4 mg, and sodium cromoglycate, 10 mg, inhibited sodium metabisulphite induced bronchoconstriction but nedocromil sodium was significantly more effective. Relative in vivo potency of the two drugs is broadly in line with other in vivo and in vitro studies. PMID:2171616

  13. Inhibition Of Washed Sludge With Sodium Nitrite

    SciTech Connect

    Congdon, J. W.; Lozier, J. S.

    2012-09-25

    This report describes the results of electrochemical tests used to determine the relationship between the concentration of the aggressive anions in washed sludge and the minimum effective inhibitor concentration. Sodium nitrate was added as the inhibitor because of its compatibility with the DWPF process. A minimum of 0.05M nitrite is required to inhibit the washed sludge simulant solution used in this study. When the worst case compositions and safety margins are considered, it is expected that a minimum operating limit of nearly 0.1M nitrite will be specified. The validity of this limit is dependent on the accuracy of the concentrations and solubility splits previously reported. Sodium nitrite additions to obtain 0.1M nitrite concentrations in washed sludge will necessitate the additional washing of washed precipitate in order to decrease its sodium nitrite inhibitor requirements sufficiently to remain below the sodium limits in the feed to the DWPF. Nitrite will be the controlling anion in "fresh" washed sludge unless the soluble chloride concentration is about ten times higher than predicted by the solubility splits. Inhibition of "aged" washed sludge will not be a problem unless significant chloride dissolution occurs during storage. It will be very important tomonitor the composition of washed sludge during processing and storage.

  14. Ultrafast and Highly Reversible Sodium Storage in Zinc-Antimony Intermetallic Nanomaterials

    SciTech Connect

    Nie, Anmin; Gan, Li-yong; Cheng, Yingchun; Tao, Xinyong; Yuan, Yifei; Sharifi-Asl, Soroosh; He, Kun; Asayesh-Ardakani, Hasti; Vasiraju, Venkata; Lu, Jun; Mashayek, Farzad; Klie, Robert; Vaddiraju, Sreeram; Schwingenschlögl, Udo; Shahbazian-Yassar, Reza

    2015-12-17

    The progress on sodium-ion battery technology faces many grand challenges, one of which is the considerably lower rate of sodium insertion/deinsertion in electrode materials due to the larger size of sodium (Na) ions and complicated redox reactions compared to the lithium-ion systems. Here, it is demonstrated that sodium ions can be reversibly stored in Zn-Sb intermetallic nanowires at speeds that can exceed 295 nm s-1. Remarkably, these values are one to three orders of magnitude higher than the sodiation rate of other nanowires electrochemically tested with in situ transmission electron micro­scopy. It is found that the nanowires display about 161% volume expansion after the first sodiation and then cycle with an 83% reversible volume expansion. Despite their massive expansion, the nanowires can be cycled without any cracking or facture during the ultrafast sodiation/desodiation process. Additionally, most of the phases involved in the sodiation/desodiation process possess high electrical conductivity. More specifically, the NaZnSb exhibits a layered structure, which provides channels for fast Na+ diffusion. This observation indicates that Zn-Sb intermetallic nanomaterials offer great promise as high rate and good cycling stability anodic materials for the next generation of sodium-ion batteries.

  15. Antimony quantification in Leishmania by electrothermal atomic absorption spectroscopy.

    PubMed

    Roberts, W L; Rainey, P M

    1993-05-15

    Tri- and pentavalent antimony were quantified in Leishmania mexicana pifanoi amastigotes and promastigotes by atomic absorption spectroscopy with electrothermal atomization. Leishmania grown in axenic culture were treated with either potassium antimony tartrate [Sb(III)] or sodium stibogluconate [Sb(V)]. The parasites were collected, digested with nitric acid, and subjected to atomic absorption spectroscopy. The method was linear from 0 to 7 ng of antimony. The interassay coefficients of variation were 9.6 and 5.7% (N = 5) for 0.52 and 3.7-ng samples of leishmanial antimony, respectively. The limit of detection was 95 pg of antimony. The assay was used to characterize Sb(III) and Sb(V) influx and efflux kinetics. Influx rates were determined at antimony concentrations that produced a 50% inhibition of growth (IC50). The influx rates of Sb(V) into amastigotes and promastigotes were 4.8 and 12 pg/million cells/h, respectively, at 200 micrograms antimony/ml. The influx rate of Sb(III) into amastigotes was 41 pg/million cells/h at 20 micrograms antimony/ml. Influx of Sb(III) into promastigotes at 1 microgram antimony/ml was rapid and reached a plateau of 175 pg/million cells in 2 h. Efflux of Sb(III) and Sb(V) from amastigotes and promastigotes exhibited biphasic kinetics. The initial (alpha) half-life of Sb(V) efflux was less than 4 min and that of Sb(III) was 1-2 h. The apparent terminal (beta) half-lives ranged from 7 to 14 h.

  16. Antimony Toxicity

    PubMed Central

    Sundar, Shyam; Chakravarty, Jaya

    2010-01-01

    Antimony toxicity occurs either due to occupational exposure or during therapy. Occupational exposure may cause respiratory irritation, pneumoconiosis, antimony spots on the skin and gastrointestinal symptoms. In addition antimony trioxide is possibly carcinogenic to humans. Improvements in working conditions have remarkably decreased the incidence of antimony toxicity in the workplace. As a therapeutic, antimony has been mostly used for the treatment of leishmaniasis and schistosomiasis. The major toxic side-effects of antimonials as a result of therapy are cardiotoxicity (~9% of patients) and pancreatitis, which is seen commonly in HIV and visceral leishmaniasis co-infections. Quality control of each batch of drugs produced and regular monitoring for toxicity is required when antimonials are used therapeutically. PMID:21318007

  17. Antimony Nanocrystals Encapsulated in Carbon Microspheres Synthesized by a Facile Self-Catalyzing Solvothermal Method for High-Performance Sodium-Ion Battery Anodes.

    PubMed

    Qiu, Shen; Wu, Xianyong; Xiao, Lifen; Ai, Xinping; Yang, Hanxi; Cao, Yuliang

    2016-01-20

    Antimony/carbon (Sb@C) microspheres are initially synthesized via a facile self-catalyzing solvothermal method, and their applicability as anode materials for sodium-ion batteries is investigated. The structural and morphological characterizations reveal that Sb@C microspheres are composed of Sb nanoparticles (∼20 nm) homogeneously encapsulated in the C matrix. The self-catalyzing solvothermal mechanism is verified through comparative experiments by using different raw materials. The as-prepared Sb@C microspheres exhibit superior sodium storage properties, demonstrating a reversible capacity of 640 mAh g(-1), excellent rate performance, and an extended cycling stability of 92.3% capacity retention over 300 cycles, making them promising anode materials for sodium-ion batteries.

  18. Copper-antimony-red phosphorus composites as promising anode materials for sodium-ion batteries

    NASA Astrophysics Data System (ADS)

    Mun, Yoo Seok; Yoon, Younghoon; Hur, Jaehyun; Park, Min Sang; Bae, Joonwon; Kim, Ji Hyeon; Yoon, Young Soo; Yoo, In Sang; Lee, Seung Geol; Kim, Il Tae

    2017-09-01

    A novel phosphorus-based alloy composite, Sb-CuP2-C, is synthesized by a simple two-step high-energy ball milling (HEBM) method and used as an anode material for sodium-ion batteries. The HEBM process with Sb, Cu, P, and C generates Sb and CuP2 phases instead of forming Cu2Sb and P owing to the differences in binding energy among the elements, which is confirmed by density functional theory. The as-prepared Sb-CuP2-C composite consists of the electrochemically active components Sb and CuP2, which are embedded in a conductive carbon matrix, as determined by X-ray diffraction analysis and high-resolution transmission electron microscopy. The composite electrode demonstrates significantly improved cycling performance owing to the presence of both a carbon matrix, which acts as a buffer to accommodate the large volume expansion during sodiation, and a conductive metal framework of copper. The introduction of red phosphorus into the composite yields higher reversible charge capacities compared to that of a Cu2Sb-C composite. The Sb-CuP2-C electrode exhibits a high capacity retention of ∼80% even after 100 cycles. Moreover, it presents stable rate cycling performance with a capacity retention of ∼78% at 3000 mA g-1.

  19. Uptake of antimony potassium tartrate by mouse liver slices

    PubMed Central

    Smith, S. E.

    1969-01-01

    1. The uptake of 124Sb-antimony potassium tartrate by isolated mouse liver slices has been measured and found to establish high tissue: medium concentration ratios. 2. Uptake was not influenced by oxygen lack, potassium, ouabain, dinitrophenol or sodium arsenate. It was inhibited by dimercaprol and reduced at low temperature. No evidence was found of counter-transport. After subcellular fractionation, most of the radioactivity was recovered from particulate fractions. 3. Kinetic studies of uptake from media containing different concentrations of antimony suggest that uptake is due partly to diffusion and partly to a saturable binding mechanism, probably involving chelation by non-diffusible thiol groups. Saturation studies suggest that only a small proportion of thiol groups bind antimony, the remainder undergoing catalytic oxidation. PMID:5348432

  20. Modelling sodium inhibition on the anaerobic digestion process.

    PubMed

    Hierholtzer, A; Akunna, J C

    2012-01-01

    Sodium is a known process inhibitor in anaerobic systems and impacts on methanogens through an increase of osmotic pressure or complete dehydration of microorganisms. In this study, a combination of experimental and modelling approaches has been employed to determine and simulate sodium inhibition on the anaerobic digestion process. The ADM1, which has been successfully used in modelling anaerobic processes, has been modified to include an extra inhibition function that considers the effect of sodium on acetoclastic methanogens and the impact on biogas production and composition. A non-competitive inhibition function was added to the rate of acetate uptake for the model to take into account sodium toxicity. Experimental studies consisted of both batch and reactor tests to obtain parameters for model calibration and validation. The calibrated model was used to predict the effect of ammonia nitrogen on sodium toxicity. It was found that relatively low sodium levels can bring about significant levels of process inhibition in the presence of high levels of ammonia. On the other hand, where the concentration of ammonia is relatively low, the tolerance threshold for sodium ions increases. Hence, care must be taken in the use of sodium hydroxide for pH adjustment during anaerobic digestion of protein-rich substrates.

  1. INHIBITION OF VIRULENCE FACTORS OF PSEUDOMONAS AERUGINOSA BY DICLOFENAC SODIUM.

    PubMed

    Abbas, Hisham A

    2015-01-01

    Resistance of Pseudomonas aeruginosa to antibiotics is a major problem. Targeting virulence factors is an alternative option to avoid the emergence of resistance to antibiotics. The effect of sub-inhibitory concentration of diclofenac sodium on the production of virulence factors of P. aeruginosa was investigated. The virulence factors included protease, haemolysin, pyocyanin and pyoverdin, in addition to pathogenic behaviors such as swimming and twitching motilities and biofilm formation. Diclofenac sodium showed significant inhibition of virulence factors as compared to the control. Diclofenac sodium decreased twitching and swimming motilities by 29.27% and 45.36%, respectively. The percentage of inhibition of pyocyanin by diclofenac sodium was 42.32%. On the other hand, pyoverdin was inhibited to a lesser extent (36.72%). Diclofenac sodium reduced protease by 52.58% and biofilm formation by 58.37%. Moreover, haemolytic activity in the presence of diclofenac sodium was 15.64% as compared to the control (100% haemolytic activity). The inhibitory activities may be due to inhibition of quorum sensing that regulates the expression of virulence factors. This study suggests the potential for the use of diclofenac sodium as an anti-virulence agent in the treatment of Pseudomonas aeruginosa infections.

  2. Pharmacologic inhibition of intestinal sodium uptake: a gut centric approach to sodium management.

    PubMed

    Spencer, Andrew G; Greasley, Peter J

    2015-09-01

    Impaired sodium excretion in patients with chronic kidney disease (CKD) can drive fluid overload and hypertension and accelerate CKD progression. Diuretics reduce fluid overload but require residual kidney function to work. Adherence to dietary sodium restriction is generally poor. Here, we review an alternative pharmacologic strategy aimed at reducing sodium absorption from the gut. Genetic studies implicate the sodium/hydrogen exchanger isoform 3 (NHE3) as the major absorptive sodium transporter. Pharmacologic inhibition of apically expressed gut NHE3 offers the potential of reducing sodium absorption and fluid overload independent of kidney function and with better safety than systemic drugs. Two small-molecule inhibitors of NHE3 (tenapanor and SAR218034) with minimal systemic exposure reduce urinary sodium and increase stool sodium in a dose-dependent manner in rodents, with similar results observed with tenapanor in humans. These molecules also reduce blood pressure in rat models of CKD (tenapanor) and hypertension (SAR218034). Clinical trials of tenapanor in patients with CKD-related disorders are ongoing. Pharmacologic inhibition of gut NHE3 may be a viable strategy for managing sodium load in patients with CKD or with sodium-sensitive hypertension in general. Ongoing clinical trials will shed further light on the potential benefits of this approach.

  3. Inhibition of neutrophil and eosinophil induced chemotaxis by nedocromil sodium and sodium cromoglycate.

    PubMed Central

    Bruijnzeel, P. L.; Warringa, R. A.; Kok, P. T.; Kreukniet, J.

    1990-01-01

    1. Neutrophils and eosinophils infiltrate the airways in association with the allergen-induced late phase asthmatic reaction. Mobilization of these cells takes place via lipid-like and protein-like chemotactic factors. In this study platelet-activating factor (PAF), leukotriene B4 (LTB4), zymosan-activated serum (ZAS) and N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as illustrative examples of both groups. Chemotaxis was studied in human neutrophils and eosinophils. The inhibitory effects of nedocromil sodium and sodium cromoglycate were evaluated. 2. All chemotactic factors tested attracted neutrophils with the following rank order of activity: ZAS greater than PAF identical to FMLP identical to LTB4. Eosinophils were only mobilized by PAF, LTB4 and ZAS with the following rank order of activity: ZAS greater than PAF greater than LTB4. 3. Nedocromil sodium and sodium cromoglycate were equally active as the PAF antagonist BN 52021 in inhibiting the PAF-induced chemotaxis of neutrophils (IC50 approximately 10(-8) M). Both drugs were also equally active in inhibiting the chemotaxis of neutrophils induced by ZAS (IC50 approximately 10(-7)-10(-6) M), FMLP (IC50 approximately 10(-7) M) and LTB4 (IC50 approximately 10(-6) M). 4. Nedocromil sodium significantly inhibited the chemotaxis of eosinophils induced by PAF (IC50 approximately 10(-6) M) and LTB4 (IC50 approximately 10(-7) M). The inhibitory potency of BN 52021 was similar to that of nedocromil sodium on the PAF-induced chemotaxis of eosinophils. Sodium cromoglycate was incapable of eliciting significant inhibition of these chemotactic responses. However, sodium cromoglycate significantly inhibited the chemotaxis of eosinophils induced by ZAS (IC50 approximately 10(-7) M), whereas nedocromil sodium was ineffective. PMID:2163279

  4. Antimony trioxide

    Integrated Risk Information System (IRIS)

    Antimony trioxide ; CASRN 1309 - 64 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogeni

  5. Bacteria and acid drainage from coal refuse: inhibition by sodium lauryl sulphate and sodium benzoate

    SciTech Connect

    Dugan, P.R.; Apel, W.A.

    1983-01-01

    Studies have shown that the application of an aqueous solution of sodium lauryl sulphate and sodium benzoate to the surface of high-sulphur coal refuse inhibits the activity of iron- and sulphur-oxidising chemo-autotrophic bacteria and reduces the amount of acid drainage from the refuse. Further studies are recommended to assess the usefulness of this method for controlling formation of acid mine drainage in the field.

  6. Sub-optimal dose of Sodium Antimony Gluconate (SAG)-diperoxovanadate combination clears organ parasites from BALB/c mice infected with antimony resistant Leishmania donovani by expanding antileishmanial T-cell repertoire and increasing IFN-gamma to IL-10 ratio.

    PubMed

    Haldar, Arun Kumar; Banerjee, Subha; Naskar, Kshudiram; Kalita, Diganta; Islam, Nashreen S; Roy, Syamal

    2009-06-01

    We demonstrate that the combination of sub-optimal doses of Sodium Antimony Gluconate (SAG) and the diperoxovanadate compound K[VO(O2)2(H2O)], also designated as PV6, is highly effective in combating experimental infection of BALB/c mice with antimony resistant (Sb(R)) Leishmania donovani (LD) as evident from the significant reduction in organ parasite burden where SAG is essentially ineffective. Interestingly, such treatment also allowed clonal expansion of antileishmanial T-cells coupled with robust surge of IFN-c and concomitant decrease in IL-10 production. The splenocytes from the treated animals generated significantly higher amounts of IFN-c inducible parasiticidal effector molecules like superoxide and nitric oxide as compared to the infected group. Our study indicates that the combination of sub-optimal doses of SAG and PV6 may be beneficial for the treatment of SAG resistant visceral leishmaniasis patients.

  7. Inhibiting persistent inward sodium currents prevents myotonia.

    PubMed

    Hawash, Ahmed A; Voss, Andrew A; Rich, Mark M

    2017-09-01

    Patients with myotonia congenita have muscle hyperexcitability due to loss-of-function mutations in the ClC-1 chloride channel in skeletal muscle, which causes involuntary firing of muscle action potentials (myotonia), producing muscle stiffness. The excitatory events that trigger myotonic action potentials in the absence of stabilizing ClC-1 current are not fully understood. Our goal was to identify currents that trigger spontaneous firing of muscle in the setting of reduced ClC-1 current. In vitro intracellular current clamp and voltage clamp recordings were performed in muscle from a mouse model of myotonia congenita. Intracellular recordings revealed a slow afterdepolarization (AfD) that triggers myotonic action potentials. The AfD is well explained by a tetrodotoxin-sensitive and voltage-dependent Na(+) persistent inward current (NaPIC). Notably, this NaPIC undergoes slow inactivation over seconds, suggesting this may contribute to the end of myotonic runs. Highlighting the significance of this mechanism, we found that ranolazine and elevated serum divalent cations eliminate myotonia by inhibiting AfD and NaPIC. This work significantly changes our understanding of the mechanisms triggering myotonia. Our work suggests that the current focus of treating myotonia, blocking the transient Na(+) current underlying action potentials, is an inefficient approach. We show that inhibiting NaPIC is paralleled by elimination of myotonia. We suggest the ideal myotonia therapy would selectively block NaPIC and spare the transient Na(+) current. Ann Neurol 2017;82:385-395. © 2017 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.

  8. Inhibition of cardiac sodium currents by toluene exposure

    PubMed Central

    Cruz, Silvia L; Orta-Salazar, Gerardo; Gauthereau, Marcia Y; Millan-Perez Peña, Lourdes; Salinas-Stefanón, Eduardo M

    2003-01-01

    Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Nav1.5 cDNA and in isolated rat ventricular myocytes. In oocytes, toluene inhibited sodium currents (INa+) in a concentration-dependent manner, with an IC50 of 274 μM (confidence limits: 141–407μM). The inhibition was complete, voltage-independent, and slowly reversible. Toluene had no effect on: (i) the shape of the I–V curves; (ii) the reversal potential of Na+; and (iii) the steady-state inactivation. The slow recovery time constant from inactivation of INa+ decreased with toluene exposure, while the fast recovery time constant remained unchanged. Block of INa+ by toluene was use- and frequency-dependent. In rat cardiac myocytes, 300 μM toluene inhibited the sodium current (INa+) by 62%; this inhibition was voltage independent. These results suggest that toluene binds to cardiac Na+ channels in the open state and unbinds either when channels move between inactivated states or from an inactivated to a closed state. The use- and frequency-dependent block of INa+ by toluene might be responsible, at least in part, for its arrhythmogenic effect. PMID:14534149

  9. Inhibition of mitotic-specific histone phophorylation by sodium arsenite

    SciTech Connect

    Cobo, J.M.; Valdez, J.G.; Gurley, L.R.

    1994-10-01

    Synchronized cultures of Chinese hamster cells (line CHO) were used to measure the effects of 10{mu}M sodium arsenite on histone phosphorylation. This treatment caused cell proliferation to be temporarily arrested, after which the cells spontaneously resumed cell proliferation in a radiomimetric manner. Immediately following treatment, it was found that sodium arsenite affected only mitotic-specific HI and H3 phosphorylations. Neither interphase, nor mitotic, H2A and H4 phosphorylations were affected, nor was interphase HI Phosphorylation affected. The phosphorylation of HI was inhibited only in mitosis, reducing HI phosphorylation to 38.1% of control levels, which was the level of interphase HI phosphorylation. The phosphorylation of both H3 variants was inhibited in mitosis, the less hydrophobic H3 to 19% and the more hydrophobic H3 to 24% of control levels. These results suggest that sodium arsenite may inhibite cell proliferation by interfering with the cyclin B/p34{sup cdc2} histone kinase activity which is thought to play a key role in regulating the cell cycle. It has been proposed by our laboratory that HI and H3 phosphorylations play a role in restructuring interphase chromatin into metaphase chromosomes. Interference of this process by sodium arsenite may lead to structurally damaged chromosomes resulting in the increased cancer risks known to be produced by arsenic exposure from the environment.

  10. Preparation, crystal structures and rapid hydration of P2- and P3-type sodium chromium antimony oxides

    SciTech Connect

    Pospelov, A.A.; Nalbandyan, V.B.

    2011-05-15

    Two new Na{sub x}[Cr{sub (1+x)/2}Sb{sub (1-x)/2}]O{sub 2} compounds have been prepared by solid-state reactions in argon. Their structures have been determined by the X-ray Rietveld method. Both new phases together with NaCrO{sub 2}-based solid solution comprise brucite-like layers of edge-shared (Cr,Sb)O{sub 6} octahedra but differ by packing mode of the layers and coordination of the interlayer Na{sup +} ions. A P3 phase exists at x{approx}0.5-0.58. It is rhombohedral (R3-bar m), a=2.966, c=16.937 A at x{approx}0.58, with 29% Na{sup +} occupancy of trigonal prisms. A P2 phase exists at x{approx}0.6-0.7. It is hexagonal (P6{sub 3}/mmc), a=2.960, c=11.190 A at x{approx}0.7, with 37% and 33% Na{sup +} occupancy of two non-equivalent trigonal prisms. Both P2 and P3 phases rapidly absorb moisture in air; packing mode is preserved, the a parameter changes slightly but c increases by 24-25%. Very high sodium ion conductivity is predicted for both P2 and P3 anhydrous phases. -- Graphical Abstract: Polyhedral presentation of layered structures of Na{sub x}[Cr{sub (1+x)/2}Sb{sub (1-x)/2}]O{sub 2}. (Cr,Sb)O{sub 6} octahedra are green. Part of the sodium prisms are open to show short distances between sodium sites which cannot be occupied simultaneously. Display Omitted highlights: > Two new layered Na{sub x}[Cr{sub (1+x)/2}Sb{sub (1-x)/2}]O{sub 2} phases, P2 and P3, have been prepared in argon. > Interlayer O-O distances are larger than in Na{sub x}(M,Ti)O{sub 2} analogs (M=Cr,Ni,Li). > As a result, both rapidly hydrate in air with c-axis expansion of 24-25%. > Bottleneck radii are also larger, and this predicts very high Na{sup +}-ion conductivity.

  11. The Membrane Electrowinning Separation of Antimony from a Stibnite Concentrate

    NASA Astrophysics Data System (ADS)

    Yang, Jian-Guang; Yang, Sheng-Hai; Tang, Chao-Bo

    2010-06-01

    The main purpose of this study was to characterize and to extract antimony from a stibnite concentrate through electrowinning. This article reports an account of a study conducted on the optimization of the process parameters for antimony pentachloride circular leaching, purification, and electrowinning of antimony from antimony trichloride solution. The effect of electrowinning parameters, such as antimony and sodium chloride concentration in the catholyte, temperature, current density, polar distance, etc., on the voltage requirement and the current efficiency (CE) of antimony electrodeposition was explored. A maximum CE of more than 97 pct was attained with a catholyte composition of 70-g/L antimony, 25-g/L NaCl, 4.5-mol/L hydrogen ion concentration, with an anolyte composition of 40-g/L antimony trichloride at a temperature of 328 K (55 °C), a 4-cm polar distance, and a cathode current density of 200 A/m2. Under the optimized conditions, the CE was more than 97 pct, and a 99.98 pct antimony plate was obtained on the cathode. The chemical content analysis of the resulting anolyte was indicated to be 97 pct antimony pentachloride and 3 pct antimony trichloride, which could be recycled to leaching tank as the leaching agent.

  12. Sodium Fluoride Inhibits MMP-2 and MMP-9

    PubMed Central

    Kato, M.T.; Bolanho, A.; Zarella, B.L.; Salo, T.; Tjäderhane, L.; Buzalaf, M.A.R.

    2014-01-01

    The importance of fluoride (F) in preventing dental caries by favorably interfering in the demineralization-remineralization processes is well-established, but its ability to inhibit matrix metalloproteinases (MMPs), which could also help to prevent dentin caries, has not been investigated. This study assessed the ability of F to inhibit salivary and purified human gelatinases MMPs-2 and -9. Saliva was collected from 10 healthy individuals. Pooled saliva was centrifuged, and supernatants were incubated for 1 hr at 37°C and subjected to zymography. Sodium fluoride (50-275 ppm F) was added to the incubation buffer. The reversibility of the inhibition of MMPs-2 and -9 by NaF was tested by the addition of NaF (250-5,000 ppm F) to the incubation buffer, after which an additional incubation was performed in the absence of F. F decreased the activities of pro- and active forms of salivary and purified human MMPs in a dose-response manner. Purified gelatinases were completely inhibited by 200 ppm F (IC50 = 100 and 75 ppm F for MMPs-2 and -9, respectively), and salivary MMP-9 by 275 ppm F (IC50 = 200 ppm F). Inhibition was partially reversible at 250-1,500 ppm F, but was irreversible at 5,000 ppm F. This is the first study to describe the ability of NaF to inhibit MMPs completely. PMID:24196489

  13. Inhibition of apple polyphenol oxidase activity by sodium chlorite.

    PubMed

    Lu, Shengmin; Luo, Yaguang; Feng, Hao

    2006-05-17

    Sodium chlorite (SC) was shown to have strong efficacy both as a sanitizer to reduce microbial growth on produce and as a browning inhibitor on fresh-cut apples in previous experiments. This study was undertaken to investigate the inhibitory effect of SC on polyphenol oxidase (PPO) and the associated mechanisms. The experiment showed that SC had a strong inhibition of apple PPO. The extent of inhibition was influenced by SC concentration and pH. Inhibition was most prominent at pH 4.5, at which approximately 30% of enzyme activity was lost in the presence of 10 mM SC, followed closely by that at pH 4.0 with a 26% reduction in PPO activity. The inhibition mode was determined using Dixon and Lineweaver-Burk plots, which established SC to be a mixed inhibitor of apple PPO for the oxidation of catechol. Preincubation of PPO with 8 mM SC for 8 min caused a maximum of 46% activity reduction compared to noninhibited control. However, preincubation of SC with catechol for 8 min resulted in no additional loss of PPO activity. These findings provide further evidence that the inhibition of PPO activity by SC is due to the inhibition of the enzyme itself rather than removal of the substrate.

  14. Hypertonic saline inhibits luminal sodium channels in respiratory epithelium.

    PubMed

    Hebestreit, Alexandra; Kersting, Ulrich; Hebestreit, Helge

    2007-05-01

    Physical exercise with increased ventilation leads to a considerable rise in water loss from the airways. The mechanisms underlying the regulation of transepithelial fluid transport necessary to compensate for these losses are unknown but may include changes in luminal ion channel conductance. The present study was designed to examine the effects of an increase in luminal chloride and sodium concentrations which may locally occur during hyperventilation on luminal ion conductance in the respiratory epithelium of healthy controls and patients diagnosed with cystic fibrosis (CF). Changes in luminal chloride and sodium conductance were inferred by recording nasal potential difference in eight healthy subjects and 10 patients with CF, using superfusing solutions based on isotonic saline (150 mM) on one occasion and solutions based on hypertonic saline (300 mM) on the other. Switching from isotonic to hypertonic saline superfusion decreased potential difference in controls and CF patients significantly. Amiloride induced a decrease of potential difference which was larger with isotonic than with hypertonic saline (controls 9.5 +/- 6.1 vs. 3.7 +/- 4.6 mV; CF 17.2 +/- 7.2 vs. 9.8 +/- 7.6 mV). Chloride conductance stimulated with solutions low in chloride and containing isoproterenol was not significantly changed by hypertonic saline solutions compared with isotonic solutions in both groups. The findings indicate a significant inhibition of luminal sodium conductance by high luminal sodium concentrations. This mechanism may be involved in the regulation of fluid transport across the respiratory epithelium during exercise and in the improvement of mucociliary clearance and lung functions with inhalation of hypertonic saline in CF.

  15. Sensitivity of Leishmania viannia panamensis to Pentavalent Antimony Is Correlated with the Formation of Cleavable DNA-Protein Complexes

    PubMed Central

    Lucumi, Armando; Robledo, Sara; Gama, Vivian; Saravia, Nancy G.

    1998-01-01

    The emergence of Leishmania less sensitive to pentavalent antimonial agents (SbVs), the report of inhibition of purified topoisomerase I of Leishmania donovani by sodium stibogluconate (Pentostam), and the uncertain mechanism of action of antimonial drugs prompted an evaluation of SbVs in the stabilization of cleavable complexes in promastigotes of Leishmania (Viannia). The effect of camptothecin, an inhibitor of topoisomerase, and additive-free meglumine antimoniate (Glucantime) on the stabilization of cleavable DNA-protein complexes associated with the inhibition of topoisomerase was assessed in the human promonocytic cell line U-937, promastigotes of L. (Viannia) panamensis selected for SbV resistance in vitro, and the corresponding wild-type strain. The stabilization of cleavable complexes and the 50% effective dose (ED50) of SbVs for parasites isolated from patients with relapses were also evaluated. The median ED50 for the wild-type strain was 16.7 μg of SbV/ml, while that of the line selected for resistance was 209.5 μg of SbV/ml. Treatment with both meglumine antimoniate and sodium stibogluconate (20 to 200 μg of SbV/ml) stabilized DNA-protein complexes in the wild-type strain but not the resistant line. The ED50s of the SbVs for Leishmania strains from patients with relapses was comparable to those for the line selected for in vitro resistance, and DNA-protein complexes were not stabilized by exposure to meglumine antimoniate. Cleavable complexes were observed in all Leishmania strains treated with camptothecin. Camptothecin stabilized cleavable complexes in U-937 cells; SbVs did not. The selective effect of the SbVs on the stabilization of DNA-protein complexes in Leishmania and the loss of this effect in naturally resistant or experimentally derived SbV-resistant Leishmania suggest that topoisomerase may be a target of antimonial drugs. PMID:9687395

  16. Inhibition of mast cell-dependent anaphylaxis by sodium salicylate

    PubMed Central

    Kim, H M; Shin, H Y; Choo, Y K; Park, J K

    1999-01-01

    Sodium salicylate (NaSal) is a commonly used agent with a wide pharmacological spectrum. The objective of the present study was to investigate the effect of NaSal on anaphylaxis. NaSal (10−1 and 1 mm) significantly inhibited systemic anaphylaxis induced by compound 48/80 in rats. NaSal also significantly inhibited local anaphylaxis activated by anti-dinitrophenyl (DNP) immunoglobulin E (IgE). NaSal (10−1 and 1 mm) significantly inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. Northern-blot analysis demonstrated that a significantly reduced level of the mRNA of l-histidine decarboxylase was expressed in mast cells treated with NaSal, compared with that without NaSal. NaSal (10−2 and 10−1 mm) had a significant inhibitory effect on anti-DNP IgE-induced tumour necrosis factor-α secretion from RPMC. The level of cyclic AMP in RPMC, when NaSal (1 mm) was added, transiently and significantly increased about sixfold compared with that of basal cells. These results suggest a possible use of NaSal in managing mast cell-dependent anaphylaxis. PMID:10233741

  17. [Sodium houttuyfonate inhibits virulence related motility of Pseudomonas aeruginosa].

    PubMed

    Wu, Da-qiang; Huang, Wei-feng; Duan, Qiang-jun; Cheng, Hui-juan; Wang, Chang-zhong

    2015-04-01

    Sodium houttuyfonate (SH) is a derivative of effective component of a Chinese material medica, Houttuynia cordata, which is applied in anti-infection of microorganism. But, the antimicrobial mechanisms of SH still remain unclear. Here, we firstly discovered that SH effectively inhibits the three types of virulence related motility of.Pseudomonas aeruginosa, i.e., swimming, twitching and swarming. The plate assay results showed that the inhibitory action of SH against swimming and twitching in 24 h and swarming in 48 h is dose-dependent; and bacteria nearly lost all of the motile activities under the concentration of 1 x minimum inhibitory concentration (MIC) (512 mg x L(-1) same as azithromycin positive group (1 x MIC, 16 mg x L(-1)). Furthermore, we found that the expression of structural gene flgB and pilG is down-regulated by SH, which implies that inhibitory mechanism of SH against motility of P. aeruginosa may be due to the inhibition of flagella and pili bioformation of P. aeruginosa by SR Therefore, our presented results firstly demonstrate that SH effectively inhibits the motility activities of P. aeruginosa, and suggest that SH could be a promising antipseudomonas agents in clinic.

  18. Inhibition of aspirin-induced bronchoconstriction by sodium cromoglycate inhalation.

    PubMed Central

    Martelli, N A; Usandivaras, G

    1977-01-01

    Five patients with asthma and severe aspirin hypersensitivity were challenged on separate days with increasing doses of aspirin given by mouth, starting with 5 mg, until a reduction in FEV1 greater than 15% was obtained. Sodium cromoglycate in doses of 20-40 mg inhibited the bronchoconstrictive reaction not only when inhaled before the challenge but also after it, at a time when progressive reduction in FEV1 values was taking place. According to these results, it seems reasonable to postulate sequential mast cell degranulation and liberation of mediators of anaphylaxis as the mechanism through which aspirin induces bronchoconstriction in aspirin-sensitive asthmatics. The differences between bronchial provocation tests and oral challenge with aspirin are stressed. PMID:414371

  19. On line automated system for the determination of Sb(V), Sb(III), thrimethyl antimony(v) and total antimony in soil employing multisyringe flow injection analysis coupled to HG-AFS.

    PubMed

    Silva Junior, Mario M; Portugal, Lindomar A; Serra, Antonio M; Ferrer, Laura; Cerdà, Victor; Ferreira, Sergio L C

    2017-04-01

    This paper proposes the use of a multisyringe flow injection analysis (MSFIA) system for inorganic antimony speciation analysis, trimethyl antimony(V) and determination of total antimony in soil samples using hydride generation atomic fluorescence spectrometry (HG-AFS). Total antimony has been determined after reduction of antimony(V) to antimony(III) using potassium iodide and ascorbic acid. For determination of total inorganic antimony the sample is percolated in a mini-column containing the Dowex 50W-X8 resin for retention of the organic species of antimony. Antimony(III) is quantified in presence of 8-hydroxyquinoline as masking agent for antimony(V) after an extraction step of the organic antimony species using the also same mini-column. The trimethyl antimony(V) content is found by difference between total antimony and total inorganic antimony. By other hand, antimony(V) is quantified by difference between total inorganic antimony and antimony(III). The analytical determinations were performed using sodium tetrahydroborate as reducing agent. The optimization step was performed using two-level full factorial design and Doehlert matrix involving the factors: hydrochloric acid and sodium tetrahydroborate concentrations and sample flow rate. The optimized experimental conditions allow the antimony determination utilizing the external calibration technique with limits of detection and quantification of 0.9 and 3.1ngg(-1), respectively, and a precision expressed as relative standard deviation of 3.2% for an antimony solution of 5.0µgL(-1). The method accuracy was confirmed by analysis of the soil certified reference material furnished from Sigma-Aldrich RTC. Additionally, addition/recovery tests were performed employing synthetic solutions prepared using trimethyl antimony(V), antimony(III), antimony(V) and five soil samples. The antimony extraction step was performed in a closed system using hydrochloric acid, ultrasonic radiation and controlled temperature. The

  20. Antimony: a flame fighter

    USGS Publications Warehouse

    Wintzer, Niki E.; Guberman, David E.

    2015-01-01

    In the 11th century, the word antimonium was used by medieval scholar Constantinus Africanus, but antimony metal was not isolated until the 16th century by Vannoccio Biringuccio, an Italian metallurgist. In the early 18th century, chemist Jons Jakob Berzelius chose the periodic symbol for antimony (Sb) based on stibium, which is the Latin name for stibnite.

  1. Separation of sodium-22 from irradiated targets

    DOEpatents

    Taylor, Wayne A.; Jamriska, David

    1996-01-01

    A process for selective separation of sodium-22 from an irradiated target including dissolving an irradiated target to form a first solution, contacting the first solution with hydrated antimony pentoxide to selectively separate sodium-22 from the first solution, separating the hydrated antimony pentoxide including the separated sodium-22 from the first solution, dissolving the hydrated antimony pentoxide including the separated sodium-22 in a mineral acid to form a second solution, and, separating the antimony from the sodium-22 in the second solution.

  2. Comparative trials of antimonial drugs in urinary schistosomiasis

    PubMed Central

    Davis, A.

    1968-01-01

    Chemotherapeutic trials in urinary schistosomiasis are described and discussed. Their design and conduct were based on recommended statistical techniques, now generally accepted as the most appropriate approach to the assessment of antischistosomal drugs. Randomization produced comparable host groups in whom multiple parasitic infection and radiological urinary tract damage were common. Treatment was with one of three antimonial compounds given at equivalent metallic dosage daily. Antimony sodium tartrate (AST) and antimony dimercaptosuccinate (TWSb) were equally efficient curatively but both produced many side-effects. Sodium antimonylgluconate (TSAG) was four-fifths as effective but tolerance was superior. Estimations of urinary antimony excretion showed that tissue retention of the metal was related to cure-rates and side-effects. It was concluded that none of the drugs were suitable for mass chemotherapy. More new non-toxic schistosomicides are urgently needed and for their assessment, the setting-up of multicentre trials, following international agreement on technical methods, is suggested. PMID:5302298

  3. Bradykinin-induced bronchoconstriction: inhibition by nedocromil sodium and sodium cromoglycate.

    PubMed Central

    Dixon, C M; Barnes, P J

    1989-01-01

    1. The effects of inhaled nedocromil sodium and sodium cromoglycate on bradykinin-induced bronchoconstriction have been studied in a double-blind, placebo controlled study, in eight mild asthmatic subjects. 2. The subjects attended on four occasions. Fifteen minutes after drug pre-treatment a bradykinin challenge was performed. Increasing concentrations were inhaled until a greater than 40% fall in expiratory flow at 30% of vital capacity from a partial flow volume manoeuvre (V p30) was demonstrated. 3. Inhaled bradykinin (0.06-8.0 mg ml-1) caused dose-related bronchoconstriction with the geometric mean cumulative dose causing a 40% fall in V p30 (PD40) of 0.035 (95% CI: 0.02-0.07) mumol, after placebo inhalation, which was similar to that measured before the trial (0.04: 0.02-0.09 mumol). 4. Both nedocromil sodium (4 mg) and sodium cromoglycate (10 mg) gave significant protection (P less than 0.05) against bradykinin-induced bronchoconstriction (PD40 0.37: 0.19-0.72 mumol after nedocromil sodium and 0.22: 0.11-0.49 after sodium cromoglycate). 5. Since bradykinin-induced bronchoconstriction is probably neurally mediated we conclude that both nedocromil sodium and sodium cromoglycate have an action on neural pathways which may be useful in the control of asthma symptoms. PMID:2547408

  4. [The corrosion behavior of antimony in a Ag-Sn-Cu-Sb amalgam].

    PubMed

    Weiland, M; Borrmann, S; Nossek, H

    1989-01-01

    Specimen of amalgam containing antimony were stored in solutions with different pH and different content of rhodanide until 21 days. The most antimony were solved within 24 hours. After 7 days an increase of the antimony concentration were not observed in physiological pH. An inhibition of corrosion by rhodanide existed only after incubation from 21 days. The quantity of antimony (10-21 micrograms) were analysed by mean of atomic absorption spectroscopy. It represent not a risk for the health. The natural presence of this element in environment and in human body is discussed to the analysed quantity of solved antimony.

  5. METAMORPHIC INHIBITION OF XENOPUS LAEVIS BY SODIUM PERCHLORATE: EFFECTS ON DEVELOPMENT AND THYROID HISTOLOGY

    EPA Science Inventory

    The perchlorate anion inhibits thyroid hormone (TH) synthesis via inhibition of the sodium-iodide symporter. It is, therefore, a good model chemical to aid in the development of a bioassay to screen chemicals for effects on thyroid function. Xenopus laevis larvae were exposed to ...

  6. Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease.

    PubMed

    Torres, V E; Wilson, D M; Burnett, J C; Johnson, C M; Offord, K P

    1991-10-01

    We compared the tubular transport of sodium and the erythrocyte sodium-lithium countertransport activity in hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) and in normotensive control subjects. In addition, we assessed the effects of inhibition of converting enzyme on renal hemodynamics and sodium excretion in hypertensive patients with ADPKD to provide information on mechanisms responsible for the increased renal vascular resistance and filtration fraction and the adjustment of the pressure-natriuresis relationship during saline expansion, observed in patients with ADPKD, hypertension, and preserved renal function. In comparison with normotensive control subjects, the hypertensive patients with ADPKD had lower renal plasma flows, higher renal vascular resistances and filtration fractions, and similar proximal and distal fractional reabsorptions of sodium. The administration of enalapril resulted in significant increases in the renal plasma flow and significant reductions in mean arterial pressure, renal vascular resistance, and filtration fraction, but the glomerular filtration rate remained unchanged. Despite the significant reduction in mean arterial pressure during inhibition of converting enzyme, the distal fractional reabsorption of sodium decreased while the total fractional excretion of sodium remained unchanged or increased slightly. No significant differences were detected between the normotensive control subjects and the hypertensive patients with ADPKD in erythrocyte sodium-lithium countertransport activity, plasma renin activity, plasma aldosterone concentration, or atrial natriuretic factor. These results suggest that the renal renin-angiotensin system plays a central role in the alterations in renal hemodynamics and sodium management associated with the development of hypertension in ADPKD.

  7. A mathematical model of long-term renal sympathetic nerve activity inhibition during an increase in sodium intake

    PubMed Central

    Denizhan, Yagmur; Hester, Robert

    2013-01-01

    It is well known that renal nerves directly affect renal vascular resistance, tubular sodium reabsorption, and renin secretion. Inhibition of renal sympathetic nerve activity (RSNA) decreases renal vascular resistance, tubular sodium reabsorption, and renin secretion, leading to an increase in sodium excretion. Although several studies show that inhibition of RSNA promotes sodium excretion during an acute blood volume expansion, there is limited research relating to the importance of RSNA inhibition that contributes to sodium homeostasis during a long-term increase in sodium intake. Therefore, to dissect the underlying mechanisms of sodium excretion, a mathematical model of a cardiovascular system consisting of two kidneys, each with an independent RSNA, was developed. Simulations were performed to determine the responses of RSNA and sodium excretion to an increased sodium intake. In these simulations, RSNA in the left kidney was fixed at its normal steady-state value, while RSNA in the contralateral kidney was allowed to change normally in response to the increased sodium intake. The results demonstrate that the fixed-RSNA kidney excretes less sodium than the intact-RSNA collateral kidney. Because each kidney is exposed to the same arterial pressure and circulatory hormones, the impaired sodium excretion in the absence of RSNA inhibition supports the hypothesis that RSNA inhibition contributes to natriuresis in response to a long-term increase in sodium intake. PMID:24285363

  8. Sodium acetate inhibits Staphylococcus aureus internalization into bovine mammary epithelial cells by inhibiting NF-κB activation.

    PubMed

    Wei, Zhengkai; Xiao, Chong; Guo, Changming; Zhang, Xu; Wang, Yanan; Wang, Jingjing; Yang, Zhengtao; Fu, Yunhe

    2017-06-01

    Bovine mastitis is one of the most costly and prevalent disease affecting dairy cows worldwide. It was reported that Staphylococcus aureus could internalize into bovine mammary epithelial cells (bMEC) and induce mastitis. Some short chain fatty acids (SCFA) have shown to suppress S. aureus invasion into bMEC and regulate antimicrobial peptides expression. But it has not been evaluated that sodium acetate has the similar effect. The aim of this study was to investigate the effect of sodium acetate on the invasion of bovine mammary epithelial cells (bMEC) by S. aureus. Gentamicin protection assay showed that the invasion of S. aureus into bMEC was inhibited by sodium acetate in a dose-dependent manner. Sodium acetate (0.25-5 mM) did not affect S. aureus growth and bMEC viability. The TAP gene level was decreased, while the BNBD5 mRNA level was enhanced in sodium acetate treated bMEC. In sodium acetate treated and S. aureus challenged bMEC, the TAP gene expression was increased and BNBD5 gene expression was not modified at low concentrations, but decreased at high concentrations. The Nitric oxide (NO) production of bMEC after S. aureus stimulation was decreased by sodium acetate treatment. Furthermore, sodium acetate treatment suppressed S. aureus-induced NF-κB activation in bMEC in a dose manner. In conclusion, our results suggested that sodium acetate exerts an inhibitory property on S. aureus internalization and modulates antimicrobial peptides gene expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Therapeutic effect of sodium selenite and zinc sulphate as supplementary with meglumine antimoniate( glucantime®) against cutaneous leishmaniasis in BALB/c mice.

    PubMed

    Sorkhroodi, F Zamani; Naeini, Am Alavi; Ramazani, Ar Zahraei; Ghazvini, Mr Aghaye; Mohebali, M; Keshavarz, Sa

    2010-09-01

    Successful therapy of leishmaniasis depends on effective cellular immune response. We evaluated the effectiveness of sodium selenite and zinc sulphate as known immunomodulator materials, in combination with Glucantime® in treatment of cutaneous leishmaniasis lesions resulting from Leishmania major in susceptible animal model. Thirty three female mice weighing 18-20 g at the age of 7-8 week infected with L. major were randomly divided into 3 groups: group1: treated by sodium selenite (0.35 mg/kg for 30 days), group2: treated by zinc sulphate (2 mg/kg for 30 days) and group3: treated by distilled water (0.01 ml/gr body weight for 30 days) as control. All groups received Glucantime® as a standard anti- leishmanial agent (60 mg/kg, ip) for 14 days. To assess the results of treatment measurement of lesions size and parasitological tests were done weekly. The lesion sizes increased continuously in sodium selenite group.Although, in zinc group did not increase compared to baseline But with considering the time- group interaction there was no significant difference between zinc and control group during this study. There was no difference between lesion sizes and Leishmanial loads in the interventional and control groups, respectively. Sodium selenite and zinc sulphate at mentioned doses and duration of treatment did not show any treatment effect on cutaneous leishmaniasis caused by L. major in BALB/c mice. Increasing the dose of supplements and considering the follow up period after treatment can help more certain conclusion.

  10. Dopamine and Angiotensin Type 2 Receptors Cooperatively Inhibit Sodium Transport in Human Renal Proximal Tubule Cells

    PubMed Central

    Gildea, John J.; Wang, Xiaoli; Shah, Neema; Tran, Hanh; Spinosa, Michael; Van Sciver, Robert; Sasaki, Midori; Yatabe, Junichi; Carey, Robert M.; Jose, Pedro A.; Felder, Robin A.

    2012-01-01

    Little is known regarding how the kidney shifts from a sodium and water reclaiming state (antinatriuresis) to a state where sodium and water are eliminated (natriuresis). In human renal proximal tubule cells (RPTCs), sodium reabsorption is decreased by the dopamine D1-like receptors (D1R/D5R) and the angiotensin type 2 receptor (AT2R), while the angiotensin type 1 receptor increases sodium reabsorption. Aberrant control of these opposing systems is thought to lead to sodium retention and subsequently hypertension. We show that D1R/D5R stimulation increased plasma membrane AT2R 4-fold via a D1R-mediated, cAMP-coupled, and PP2A-dependent specific signaling pathway. D1R/D5R stimulation also reduced the ability of angiotensin II to stimulate phospho-ERK, an effect that was partially reversed by an AT2R antagonist. Fenoldopam did not increase AT2R recruitment in RPTCs with D1Rs uncoupled from adenylyl cyclase, suggesting a role of cAMP in mediating these events. D1Rs and AT2Rs heterodimerized and cooperatively increased cAMP and cGMP production, PP2A activation, sodium-potassium-ATPase internalization and sodium transport inhibition. These studies shed new light on the regulation of renal sodium transport by the dopaminergic and angiotensin systems and potential new therapeutic targets for selectively treating hypertension. PMID:22710646

  11. Dopamine and angiotensin type 2 receptors cooperatively inhibit sodium transport in human renal proximal tubule cells.

    PubMed

    Gildea, John J; Wang, Xiaoli; Shah, Neema; Tran, Hanh; Spinosa, Michael; Van Sciver, Robert; Sasaki, Midori; Yatabe, Junichi; Carey, Robert M; Jose, Pedro A; Felder, Robin A

    2012-08-01

    Little is known regarding how the kidney shifts from a sodium and water reclaiming state (antinatriuresis) to a state where sodium and water are eliminated (natriuresis). In human renal proximal tubule cells, sodium reabsorption is decreased by the dopamine D(1)-like receptors (D(1)R/D(5)R) and the angiotensin type 2 receptor (AT(2)R), whereas the angiotensin type 1 receptor increases sodium reabsorption. Aberrant control of these opposing systems is thought to lead to sodium retention and, subsequently, hypertension. We show that D(1)R/D(5)R stimulation increased plasma membrane AT(2)R 4-fold via a D(1)R-mediated, cAMP-coupled, and protein phosphatase 2A-dependent specific signaling pathway. D(1)R/D(5)R stimulation also reduced the ability of angiotensin II to stimulate phospho-extracellular signal-regulated kinase, an effect that was partially reversed by an AT(2)R antagonist. Fenoldopam did not increase AT(2)R recruitment in renal proximal tubule cells with D(1)Rs uncoupled from adenylyl cyclase, suggesting a role of cAMP in mediating these events. D(1)Rs and AT(2)Rs heterodimerized and cooperatively increased cAMP and cGMP production, protein phosphatase 2A activation, sodium-potassium-ATPase internalization, and sodium transport inhibition. These studies shed new light on the regulation of renal sodium transport by the dopaminergic and angiotensin systems and potential new therapeutic targets for selectively treating hypertension.

  12. Corticotropin-releasing hormone in the lateral parabrachial nucleus inhibits sodium appetite in rats.

    PubMed

    De Castro e Silva, Emilio; Fregoneze, Josmara B; Johnson, Alan Kim

    2006-04-01

    The present study investigated the role of corticotropin-releasing hormone (CRH) in the lateral parabrachial nucleus (LPBN) in the behavioral control of body fluid homeostasis by determining the effect of bilateral injections of the CRH receptor antagonist, alpha-helical corticotropin-releasing factor (CRF)(9-41), and the CRH receptor agonist, CRH, on sodium chloride (salt appetite) and water (thirst) intake. Groups of adult, male Sprague-Dawley rats had stainless-steel cannulas implanted bilaterally into the LPBN and were sodium depleted or water deprived. Bilateral injections of alpha-helical CRF(9-41) into the LPBN significantly potentiated water and salt intake in the sodium-depleted rats when access to fluids was restored. Bilateral injections of alpha-helical CRF(9-41) into the LPBN (1.0 microg) also increased sodium appetite in water-deprived rats. Conversely, in sodium-depleted animals, bilateral injections of CRH inhibited sodium chloride intake. These results suggest that there is an endogenous CRH inhibitory mechanism operating in the LPBN to modulate the intake of sodium (salt appetite). This mechanism may contribute to the behavioral control of restoration of body fluid homeostasis in sodium-deficient states.

  13. Mode of Action of the Natural Insecticide, Decaleside Involves Sodium Pump Inhibition

    PubMed Central

    Rajashekar, Yallappa; Shivanandappa, Thimmappa

    2017-01-01

    Decalesides are a new class of natural insecticides which are toxic to insects by contact via the tarsal gustatory chemosensilla. The symptoms of their toxicity to insects and the rapid knockdown effect suggest neurotoxic action, but the precise mode of action and the molecular targets for decaleside action are not known. We have presented experimental evidence for the involvement of sodium pump inhibition in the insecticidal action of decaleside in the cockroach and housefly. The knockdown effect of decaleside is concomitant with the in vivo inhibition of Na+, K+ -ATPase in the head and thorax. The lack of insecticidal action by experimental ablation of tarsi or blocking the tarsal sites with paraffin correlated with lack of inhibition of Na+- K+ ATPase in vivo. Maltotriose, a trisaccharide, partially rescued the toxic action of decaleside as well as inhibition of the enzyme, suggesting the possible involvement of gustatory sugar receptors. In vitro studies with crude insect enzyme preparation and purified porcine Na+, K+ -ATPase showed that decaleside competitively inhibited the enzyme involving the ATP binding site. Our study shows that the insecticidal action of decaleside via the tarsal gustatory sites is causally linked to the inhibition of sodium pump which represents a unique mode of action. The precise target(s) for decaleside in the tarsal chemosensilla and the pathway linked to inhibition of sodium pump and the insecticidal action remain to be understood. PMID:28125742

  14. Valproic acid inhibits TTX-resistant sodium currents in prefrontal cortex pyramidal neurons.

    PubMed

    Szulczyk, Bartlomiej; Nurowska, Ewa

    2017-09-16

    Valproic acid is frequently prescribed and used to treat epilepsy, bipolar disorder and other conditions. However, the mechanism of action of valproic acid has not been fully elucidated. The aim of this study was to assess the influence of valproic acid (200 μM) on TTX-resistant sodium currents in mPFC pyramidal neurons. Valproic acid inhibited the maximal amplitude and did not change the activation parameters of TTX-resistant sodium currents. Moreover, valproic acid (2 μM and 200 μM) shifted the TTX-resistant sodium channel inactivation curve towards hyperpolarisation. In the presence of valproic acid, TTX-resistant sodium currents recovered from inactivation more slowly. Valproic acid did not influence the use-dependent blockade of TTX-resistant sodium currents. This study suggests that a potential new mechanism of the antiepileptic action of valproic acid is, among others, inhibition of TTX-resistant sodium currents. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Sodium alginate inhibits methotrexate-induced gastrointestinal mucositis in rats.

    PubMed

    Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Kajiwara, Eiji; Nishida, Ryuichi

    2013-01-01

    Gastrointestinal mucositis is one of the most prevalent side effects of chemotherapy. Methotrexate is a pro-oxidant compound that depletes dihydrofolate pools and is widely used in the treatment of leukemia and other malignancies. Through its effects on normal tissues with high rates of proliferation, methotrexate treatment leads to gastrointestinal mucositis. In rats, methotrexate-induced gastrointestinal mucositis is histologically characterized by crypt loss, callus fusion and atrophy, capillary dilatation, and infiltration of mixed inflammatory cells. The water-soluble dietary fiber sodium alginate (AL-Na) is derived from seaweed and has demonstrated muco-protective and hemostatic effects on upper gastrointestinal ulcers. In the present study, we evaluated the effects of AL-Na on methotrexate-induced small intestinal mucositis in rats. Animals were subcutaneously administered methotrexate at a dosage of 2.5 mg/kg once daily for 3 d. Rats were treated with single oral doses of AL-Na 30 min before and 6 h after methotrexate administration. On the 4th day, small intestines were removed and weighed. Subsequently, tissues were stained with hematoxylin-eosin and bromodeoxyuridine. AL-Na significantly prevented methotrexate-induced small intestinal mucositis. Moreover, AL-Na prevented decreases in red blood cell numbers, hemoglobin levels, and hematocrit levels. These results suggest the potential of AL-Na as a therapy for methotrexate-induced small intestinal mucositis.

  16. Sodium

    MedlinePlus

    Table salt is a combination of two minerals - sodium and chloride Your body needs some sodium to work properly. It helps with the function ... in your body. Your kidneys control how much sodium is in your body. If you have too ...

  17. Elucidation of the mechanism of enzymatic browning inhibition by sodium chlorite

    USDA-ARS?s Scientific Manuscript database

    Sodium chlorite (SC) is a well known anti-microbial agent and its strong inhibitory effect on enzymatic browning of fresh-cut produce has recently been identified. We investigated the mechanisms of browning inhibition by SC using chlorogenic acid (CA) and PPO extracted from mushroom to emulate the b...

  18. Iron ions derived from the nitric oxide donor sodium nitroprusside inhibit mineralization.

    PubMed

    Huitema, Leonie F A; van Weeren, P René; Barneveld, Ab; van de Lest, Chris H A; Helms, J Bernd; Vaandrager, Arie B

    2006-08-07

    Sodium nitroprusside (SNP) is a nitric oxide (NO) donor drug, which is therapeutically used as a vasodilating drug in heart transplantations. In our previous study it was found that SNP at a concentration of 100 microM inhibited mineralization in a cell culture system, indicating that the beneficial effects of this drug may also include inhibition of vascular calcification. The aim of this study was to investigate which bioactive compounds generated from SNP inhibit mineralization. ATDC5 cells were grown for 14 days and mineralization was induced by addition of 5 mM phosphate for 24 h. Mineralization was determined by staining precipitated calcium with an alizarin red stain. It was found that the NO donors S-nitrosoglutathione and S-nitroso-N-acetylpenicillamine were not able to inhibit mineralization and NO scavengers could not antagonize the inhibiting effect of SNP on mineralization. The iron chelator deferoxamine (200 microM) antagonized the inhibiting effect on mineralization mediated by SNP and ammonium iron sulfate inhibited mineralization in a dose-dependent manner (10-100 microM). Furthermore, iron ions (30 microM) were detected to be released from SNP in the cell culture. These data show that the iron moiety of sodium nitroprusside, rather than nitric oxide inhibits mineralization.

  19. Inhibition of platelet-activating factor- and zymosan-activated serum-induced chemotaxis of human neutrophils by nedocromil sodium, BN 52021 and sodium cromoglycate.

    PubMed Central

    Bruijnzeel, P. L.; Warringa, R. A.; Kok, P. T.

    1989-01-01

    1. Inflammatory cells such as eosinophils and neutrophils are thought to contribute actively to the pathogenesis of asthma since they infiltrate into the lung tissue. These cells are mobilized by lipid-like and protein-like chemotactic factors. As illustrative examples of both groups, platelet-activating-factor (Paf) and zymosan-activated-serum (ZAS) were used in this study. The inhibitory effects of nedocromil sodium, the Paf antagonist BN 52021 and sodium cromoglycate on Paf- and ZAS-induced neutrophil chemotaxis were evaluated. 2. All tested drugs inhibited Paf-induced neutrophil chemotaxis with approximately the same potency (IC50 approximately 1 nM). 3. Nedocromil sodium and sodium cromoglycate were equally potent in inhibiting ZAS-induced neutrophil chemotaxis (IC50 = 0.1-1 microM), whereas BN 52021 was considerably less potent (IC30 = 10 microM). 4. To find out whether the drugs tested could inhibit early events in cell activation, their capacity to inhibit Paf- and ZAS-induced cytosolic free Ca2+-mobilization was investigated. BN 52021, at a concentration of 100 microM, completely inhibited Paf-induced Ca2+-mobilization and inhibited ZAS-induced Ca2+-mobilization by about 50%. Nedocromil sodium and sodium cromoglycate were ineffective. PMID:2551444

  20. The nitric oxide donor sodium nitroprusside inhibits mineralization in ATDC5 cells.

    PubMed

    Huitema, L F A; Vaandrager, A B; van Weeren, P R; Barneveld, A; Helms, J B; van de Lest, C H A

    2006-03-01

    The aim of this study was to test whether the nitric oxide (NO) donor sodium nitroprusside (SNP) has an effect on mineralization in ATDC5 cells. Mineralization in ATDC5 cell culture was induced by addition of beta-glycerophosphate or inorganic phosphate, visualized by staining precipitated calcium with an alizarin red stain, and quantified using atomic absorption spectrometry. SNP was shown to inhibit the mineralization of ADTC5 cells. This inhibition was not affected by inhibitors of guanylyl cyclase nor mimicked by a cyclic guanosine monophosphate (cGMP) analog. Furthermore, SNP did not inhibit phosphate uptake or inhibit apoptosis in ATDC5 cells. These findings indicate that SNP can specifically inhibit matrix mineralization via a cGMP-independent pathway and that the effect is not mediated by inhibition of phosphate transport or apoptosis. These results suggest a preventive role of NO in premature or pathological mineralization.

  1. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect

    PubMed Central

    Kalra, Sanjay; Jain, Arpit; Ved, Jignesh; Unnikrishnan, A. G.

    2016-01-01

    This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a “good person,” who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production. PMID:27730088

  2. Sodium-glucose cotransporter 2 inhibition and health benefits: The Robin Hood effect.

    PubMed

    Kalra, Sanjay; Jain, Arpit; Ved, Jignesh; Unnikrishnan, A G

    2016-01-01

    This review discusses two distinct, yet related, mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition: Calorie restriction mimicry (CRM) and pro-ketogenic effect, which may explain their cardiovascular benefits. We term these adaptive CRM and pro-ketogenic effects of SGLT2 inhibition, the Robin Hood hypothesis. In English history, Robin Hood was a "good person," who stole from the rich and helped the poor. He supported redistribution of resources as he deemed fit for the common good. In a similar fashion, SGLT2 inhibition provides respite to the overloaded glucose metabolism while utilizing lipid stores for energy production.

  3. The abnormal in vitro response to aspirin of platelets from aspirin-sensitive asthmatics is inhibited after inhalation of nedocromil sodium but not of sodium cromoglycate.

    PubMed Central

    Marquette, C H; Joseph, M; Tonnel, A B; Vorng, H; Lassalle, P; Tsicopoulos, A; Capron, A

    1990-01-01

    1. Blood platelets from patients with aspirin-sensitive asthma (ASA) generated cytotoxic mediators in the presence of aspirin. This abnormal in vitro response to aspirin was abolished within 1 h after nedocromil sodium inhalation but not after sodium cromoglycate inhalation. 2. Platelets recovered this reactivity to aspirin by 12 hours after nedocromil sodium treatment of ASA-patients. 3. The in vitro reactivity to aspirin of ASA platelets isolated before inhalation was inhibited in the presence of serum isolated 15 and 60 min after nedocromil sodium inhalation. PMID:2161678

  4. Inhibition of mouse B16 melanoma by sodium butyrate correlated to tumor associated macrophages differentiation suppression

    PubMed Central

    Xiong, Fen; Mou, Yun-Zhu; Xiang, Xiao-Yan

    2015-01-01

    Objective: As one member of the histone deacetylase inhibitor (HDACi) family, Sodium butyrate (NaB) was found out that could be used as a differentiation inducer of much cancer cell. But its effects on tumor microenvironment cells are not well recognized. The goal of this research is to investigate the effect of NaB on B16 melanoma and analysis its relevant mechanism. Methods: We observed the effect of sodium butyrate on B16 melanoma in vivo and in vitro. MTT method was performed to detect cell apoptosis rate after treatment. Tumor associated macrophage infiltration condition was detected by flow cytometry. Western-blotting and immunohistochemical method were used to detect the expression of tumor associated macrophage cytokines. Results: A certain concentration of sodium butyrate could effectively inhibit B16 melanoma growth in vivo and in vitro, and this inhibition effects related to the suppression of tumor associated macrophage differentiation. At the same time we observed the relevant macrophage factors were down-regulated compared to the control. Conclusion: Sodium butyrate could effectively inhibit B16 melanoma growth through suppressing tumor associated macrophage proliferation and reduce relevant pro-tumor macrophage factors expression, which may help to promote the clinical study of melanoma epigenetic therapy. PMID:26064327

  5. Epitaxial Silicon Doped With Antimony

    NASA Technical Reports Server (NTRS)

    Huffman, James E.; Halleck, Bradley L.

    1996-01-01

    High-purity epitaxial silicon doped with antimony made by chemical vapor deposition, using antimony pentachloride (SbCI5) as source of dopant and SiH4, SiCI2H2, or another conventional source of silicon. High purity achieved in layers of arbitrary thickness. Epitaxial silicon doped with antimony needed to fabricate impurity-band-conduction photodetectors operating at wavelengths from 2.5 to 40 micrometers.

  6. Epitaxial Silicon Doped With Antimony

    NASA Technical Reports Server (NTRS)

    Huffman, James E.; Halleck, Bradley L.

    1996-01-01

    High-purity epitaxial silicon doped with antimony made by chemical vapor deposition, using antimony pentachloride (SbCI5) as source of dopant and SiH4, SiCI2H2, or another conventional source of silicon. High purity achieved in layers of arbitrary thickness. Epitaxial silicon doped with antimony needed to fabricate impurity-band-conduction photodetectors operating at wavelengths from 2.5 to 40 micrometers.

  7. Immobilization of antimony waste slag by applying geopolymerization and stabilization/solidification technologies.

    PubMed

    Salihoglu, Güray

    2014-11-01

    During the processing of antimony ore by pyrometallurgical methods, a considerable amount of slag is formed. This antimony waste slag is listed by the European Union as absolutely hazardous waste with a European Waste Catalogue code of 10 08 08. Since the levels of antimony and arsenic in the leachate of the antimony waste slag are generally higher than the landfilling limits, it is necessary to treat the slag before landfilling. In this study, stabilization/solidification and geopolymerization technologies were both applied in order to limit the leaching potential of antimony and arsenic. Different combinations ofpastes by using Portland cement, fly ash, clay, gypsum, and blast furnace slag were prepared as stabilization/solidification or geopoljymer matrixes. Sodium silicate-sodium hydroxide solution and sodium hydroxide solution at 8 M were used as activators for geopolymer samples. Efficiencies of the combinations were evaluated in terms of leaching and unconfined compressive strength. None of the geopolymer samples prepared with the activators yielded arsenic and antimony leaching below the regulatory limit at the same time, although they yielded high unconfined compressive strength levels. On the other hand, the stabilization/solidification samples prepared by using water showed low leaching results meeting the landfilling criteria. Use of gypsum as an additive was found to be successful in immobilizing the arsenic and antimony.

  8. Tetrodotoxin-sensitive α-subunits of voltage-gated sodium channels are relevant for inhibition of cardiac sodium currents by local anesthetics.

    PubMed

    Stoetzer, C; Doll, T; Stueber, T; Herzog, C; Echtermeyer, F; Greulich, F; Rudat, C; Kispert, A; Wegner, F; Leffler, A

    2016-06-01

    The sodium channel α-subunit (Nav) Nav1.5 is regarded as the most prevalent cardiac sodium channel required for generation of action potentials in cardiomyocytes. Accordingly, Nav1.5 seems to be the main target molecule for local anesthetic (LA)-induced cardiotoxicity. However, recent reports demonstrated functional expression of several "neuronal" Nav's in cardiomyocytes being involved in cardiac contractility and rhythmogenesis. In this study, we examined the relevance of neuronal tetrodotoxin (TTX)-sensitive Nav's for inhibition of cardiac sodium channels by the cardiotoxic LAs ropivacaine and bupivacaine. Effects of LAs on recombinant Nav1.2, 1.3, 1.4, and 1.5 expressed in human embryonic kidney cell line 293 (HEK-293) cells, and on sodium currents in murine, cardiomyocytes were investigated by whole-cell patch clamp recordings. Expression analyses were performed by reverse transcription PCR (RT-PCR). Cultured cardiomyocytes from neonatal mice express messenger RNA (mRNA) for Nav1.2, 1.3, 1.5, 1.8, and 1.9 and generate TTX-sensitive sodium currents. Tonic and use-dependent block of sodium currents in cardiomyocytes by ropivacaine and bupivacaine were enhanced by 200 nM TTX. Inhibition of recombinant Nav1.5 channels was similar to that of TTX-resistant currents in cardiomyocytes but stronger as compared to inhibition of total sodium current in cardiomyocytes. Recombinant Nav1.2, 1.3, 1.4, and 1.5 channels displayed significant differences in regard to use-dependent block by ropivacaine. Finally, bupivacaine blocked sodium currents in cardiomyocytes as well as recombinant Nav1.5 currents significantly stronger in comparison to ropivacaine. Our data demonstrate for the first time that cardiac TTX-sensitive sodium channels are relevant for inhibition of cardiac sodium currents by LAs.

  9. Reductive precipitation of metals photosensitized by tin and antimony porphyrins

    DOEpatents

    Shelnutt, John A.; Gong, Weiliang; Abdelouas, Abdesselam; Lutze, Werner

    2003-09-30

    A method for reducing metals using a tin or antimony porphyrin by forming an aqueous solution of a tin or antimony porphyrin, an electron donor, such as ethylenediaminetetraaceticacid, triethylamine, triethanolamine, and sodium nitrite, and at least one metal compound selected from a uranium-containing compound, a mercury-containing compound, a copper-containing compound, a lead-containing compound, a gold-containing compound, a silver-containing compound, and a platinum-containing compound through irradiating the aqueous solution with light.

  10. Inhibition of Salmonella Enteritidis by cerein 8A, EDTA and sodium lactate.

    PubMed

    Lappe, Rosiele; Motta, Amanda S; Sant'anna, Voltaire; Brandelli, Adriano

    2009-11-15

    The ability of the bacteriocin cerein 8A to inhibit Salmonella Enteritidis in combination with EDTA and sodium lactate was investigated. Salmonella Enteritidis was incubated with combinations of cerein 8A (3200AU/mL) and EDTA (20, 50, 100 mmol/L) or sodium lactate (200 mmol/L). All treatments caused a significant reduction in the OD(600) values of Salmonella Enteritidis cultures. The addition of cerein 8A plus EDTA resulted in higher inhibition in comparison with the bacteriocin alone; the greater the concentration of EDTA, the greater the inhibitory effect. The combination of cerein 8A plus 100 mmol/L EDTA results in a more efficient treatment to reduce the number of viable cells of Salmonella Enteritidis. The combination of cerein 8A plus sodium lactate also showed significant inhibition of the indicator organism. Transmission electron microscopy showed damaged cell walls and loss of protoplasmic material in treated cells. The cells of Salmonella Enteritidis treated with cerein 8A plus EDTA appeared more injured. The bacteriocin cerein 8A may be useful to inhibit Gram-negative bacteria, with enhanced effect in combination with chelating agents. Control of Salmonella Enteritidis, a Gram-negative bacterium constantly linked to food outbreaks, addresses an important aspect of food safety.

  11. Curcumin/turmeric solubilized in sodium hydroxide inhibits HNE protein modification--an in vitro study.

    PubMed

    Kurien, Biji T; Scofield, R Hal

    2007-03-21

    Free radical mediated lipid peroxidation has been implicated in multiple diseases. A major oxidation by-product of this deleterious process is 4-hydroxy-2-nonenal (HNE). HNE is cytotoxic, mutagenic and genotoxic and is involved in disease pathogenesis. Curcumin, a non-steroidal anti-inflammatory agent (occurring as the yellow pigment found in the rhizomes of the perennial herb Curcuma longa known as turmeric), has emerged as the newest "nutraceutical" agent that has been shown to be efficacious against colon cancer and other disorders, including correcting cystic fibrosis defects. Since curcumin has been reported to have anti-oxidant properties we hypothesized that it will inhibit HNE-modification of a protein substrate. Using an ELISA that employed HNE-modification of solid phase antigen following immobilization, we found that the curcumin solubilized in dilute alkali (5mM sodium hydroxide, pH 11) inhibited HNE-protein modification by 65%. Turmeric also inhibited HNE-protein modification similarly (65%) but at a much lower alkali level (130muM sodium hydroxide, pH 7.6). Alkali by itself (5mM sodium hydroxide, pH 11) was found to enhance HNE modification by as much as 267%. Curcumin/turmeric has to inhibit this alkali enhanced HNE-modification prior to inhibiting the normal HNE protein modification induced by HNE. Thus, inhibition of HNE-modification could be a mechanism by which curcumin exerts its antioxidant effects. The pH at which the inhibition of HNE modification of substrate was observed was close to the physiological pH, making this formulation of curcumin potentially useful practically.

  12. Sodium-glucose cotransporter-2 inhibition and the insulin: Glucagon ratio: Unexplored dimensions

    PubMed Central

    Kalra, Sanjay; Gupta, Yashdeep; Patil, Shiva

    2015-01-01

    The sodium-glucose cotransporter 2 (SGLT-2) inhibitors are a novel class of glucose-lowering drugs which act by inhibiting the reabsorption of filtered glucose from the kidneys. Their effect on insulin and glucagon levels has recently been studied but is not fully explained. This communication proposes various hypotheses: A direct effect of SGLT-2 inhibition on the alpha cell receptors, a paracrine or intra-islet mediated effect on alpha cell sensitivity to glucose, and a calorie restriction mimetic action, to explain the impact of these drugs on the insulin glucagon ratio. PMID:25932403

  13. Recent advances on antimony(III/V) compounds with potential activity against tumor cells.

    PubMed

    Hadjikakou, S K; Ozturk, I I; Banti, C N; Kourkoumelis, N; Hadjiliadis, N

    2015-12-01

    Antimony one of the heavier pnictogens, has been in medical use against microbes and parasites as well. Antimony-based drugs have been prescribed against leishmaniasis since the parasitic transmission of the tropical disease was understood in the beginning of the 20th century. The activity of arsenic against visceral leishmaniasis led to the synthesis of an array of arsenic-containing parasitic agents, among them the less toxic pentavalent antimonials: Stibosan, Neostibosan, and Ureastibamine. Other antimony drugs followed: sodium stibogluconate (Pentostam) and melglumine antimoniate (Glucantim or Glucantime); both continue to be in use today despite their toxic side effects and increasing loss in potency due to the growing resistance of the parasite against antimony. Antimony compounds and their therapeutic potentials are under consideration from many research groups, while a number of early reviews recording advances of antimony biomedical applications are also available. However, there are only few reports on the screening for antitumor potential of antimony compounds. This review focuses upon results obtained on the anti-proliferative activity of antimony compounds in the past years. This survey shows that antimony(III/V) complexes containing various types of ligands such as thiones, thiosemicarbazones, dithiocarbamates, carboxylic acids, or ketones, nitrogen donor ligands, exhibit selectivity against a variety of cancer cells. The role of the ligand type of the complex is elucidated within this review. The complexes and their biological activity are already reported elsewhere. However quantitative structure-activity relationship (QSAR) modeling studies have been carried out and they are reported for the first time here. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Antimony leaching in plastics from waste electrical and electronic equipment (WEEE) with various acids and gamma irradiation

    SciTech Connect

    Tostar, Sandra; Stenvall, Erik; Boldizar, Antal; Foreman, Mark R. St. J.

    2013-06-15

    Highlights: • We have proposed a method to recover antimony from electronic plastics. • The most efficient acid solution was sodium hydrogen tartrate in dimethyl sulfoxide. • Gamma irradiation did not influence the antimony leaching ability. - Abstract: There has been a recent interest in antimony since the availability in readily mined areas is decreasing compared to the amounts used. It is important in many applications such as flame retardants and in the production of polyester, which can trigger an investigation of the leachability of antimony from plastics using different acids. In this paper, different types of acids are tested for their ability to leach antimony from a discarded computer housing, made of poly(acrylonitrile butadiene styrene), which is a common plastic type used in electrical and electronic equipment. The acid solutions included sodium hydrogen tartrate (0.5 M) dissolved in either dimethyl sulfoxide or water (at ca. 23 °C and heated to ca. 105 °C). The metal content after leaching was determined by inductively coupled plasma optical emission spectroscopy. The most efficient leaching medium was the heated solution of sodium hydrogen tartrate in dimethyl sulfoxide, which leached almost half of the antimony from the poly(acrylonitrile butadiene styrene). Gamma irradiation, which is proposed to improve the mechanical properties in plastics, was used here to investigate the influence of antimony leaching ability. No significant change in the amount of leached antimony could be observed.

  15. F 15845 inhibits persistent sodium current in the heart and prevents angina in animal models

    PubMed Central

    Vacher, B; Pignier, C; Létienne, R; Verscheure, Y; Le Grand, B

    2009-01-01

    Background and purpose: Activation of the persistent sodium current in ischaemic myocardium results in calcium overload which is toxic for the cardiomyocyte. Thus, the activity of 3-(R)-[3-(2-methoxyphenylthio-2-(S)-methylpropyl]amino-3,4-dihydro-2H-1,5 benzoxathiepine bromhydrate (F 15845), a new selective persistent sodium current blocker, in protecting against the effects of cardiac ischaemia was examined, in both in vitro and in vivo models. Experimental approach: Electrophysiological studies using patch-clamp and conventional microlelectrode techniques, isolated perfused hearts and models of angina in anaesthetized animals were used to assess the protection afforded by F 15845 against ischaemia-induced changes. Key results: F 15845 reduced the persistent sodium current activated by veratridine (IC50 1.58 × 10−6 mol·L−1). F 15845 blocked voltage-gated human cardiac sodium channels in a novel, voltage-dependent manner, selectively affecting steady-state inactivation. F 15845 did not affect action potential shape and basal function of guinea pig isolated perfused hearts but did reduce ischaemia-induced diastolic contracture in this model (IC50 0.64 × 10−6 mol·L−1). In rabbits, F 15845 given i.v. (ED50 0.05 mg·kg−1) or orally (ED50 0.13 mg·kg−1) dose-dependently and powerfully inhibited regional myocardial ischaemia-induced ST segment elevation in the absence of haemodynamic effects, implying direct cardiac activity. In dogs, F 15845 dose-dependently inhibited epicardial ST segment changes (70 ± 8% at 0.63 mg·kg−1) in an experimental angina model of demand ischaemia, again without haemodynamic effects, confirming a direct anti-anginal activity. Conclusions and implications: F 15845 is a selective, potent blocker of the persistent sodium current, generated by the human Nav1.5 channel isoforms, and prevents cardiac angina in animal models. PMID:19133985

  16. Oligosilanylated Antimony Compounds

    PubMed Central

    2015-01-01

    By reactions of magnesium oligosilanides with SbCl3, a number of oligosilanylated antimony compounds were obtained. When oligosilanyl dianions were used, either the expected cyclic disilylated halostibine was obtained or alternatively the formation of a distibine was observed. Deliberate formation of the distibine from the disilylated halostibine was achieved by reductive coupling with C8K. Computational studies of Sb–Sb bond energies, barriers of pyramidal inversion at Sb, and the conformational behavior of distibines provided insight for the understanding of the spectroscopic properties. PMID:25937691

  17. Cobalt and antimony: genotoxicity and carcinogenicity.

    PubMed

    De Boeck, Marlies; Kirsch-Volders, Micheline; Lison, Dominique

    2003-12-10

    The purpose of this review is to summarise the data concerning genotoxicity and carcinogenicity of Co and Sb. Both metals have multiple industrial and/or therapeutical applications, depending on the considered species. Cobalt is used for the production of alloys and hard metal (cemented carbide), diamond polishing, drying agents, pigments and catalysts. Occupational exposure to cobalt may result in adverse health effects in different organs or tissues. Antimony trioxide is primarily used as a flame retardant in rubber, plastics, pigments, adhesives, textiles, and paper. Antimony potassium tartrate has been used worldwide as an anti-shistosomal drug. Pentavalent antimony compounds have been used for the treatment of leishmaniasis. Co(II) ions are genotoxic in vitro and in vivo, and carcinogenic in rodents. Co metal is genotoxic in vitro. Hard metal dust, of which occupational exposure is linked to an increased lung cancer risk, is proven to be genotoxic in vitro and in vivo. Possibly, production of active oxygen species and/or DNA repair inhibition are mechanisms involved. Given the recently provided proof for in vitro and in vivo genotoxic potential of hard metal dust, the mechanistic evidence of elevated production of active oxygen species and the epidemiological data on increased cancer risk, it may be advisable to consider the possibility of a new evaluation by IARC. Both trivalent and pentavalent antimony compounds are generally negative in non-mammalian genotoxicity tests, while mammalian test systems usually give positive results for Sb(III) and negative results for Sb(V) compounds. Assessment of the in vivo potential of Sb2O3 to induce chromosome aberrations (CA) gave conflicting results. Animal carcinogenicity data were concluded sufficient for Sb2O3 by IARC. Human carcinogenicity data is difficult to evaluate given the frequent co-exposure to arsenic. Possible mechanisms of action, including potential to produce active oxygen species and to interfere with

  18. Effect of antimony on the microbial growth and the activities of soil enzymes.

    PubMed

    An, Youn-Joo; Kim, Minjin

    2009-02-01

    The effects of antimony (Sb) on microbial growth inhibition and activities of soil enzymes were investigated in the present study. Test bacterial species were Escherichia coli, Bacillus subtilis and Streptococcus aureus. Among the microorganisms tested, S. aureus was the most sensitive. The 50% effects on the inhibition of specific growth rate of E. coli, B. subtilis, and, S. aureus were 555, 18.4, and 15.8 mg Sb L(-1), respectively. A silt loam soil was amended with antimony and incubated in a controlled condition. Microbial activities of dehydrogenase, acid phosphatase (P cycle), arylsulfatase (S cycle), beta-glucosidase (C cycle), urease (N cycle), and fluorescein diacetate hydrolase in soil were measured. Activities of urease and dehydrogenase were related with antimony and can be an early indication of antimony contamination. The maximum increase in soil urease activity by antimony was up to 168% after 3d compared with the control. The activities of other four enzymes (acid phosphatase, fluorescein diacetate hydrolase, arylsulfatase and ss-glucosidase) were less affected by antimony. This study suggested that antimony affects nitrogen cycle in soil by changing urease activity under the neutral pH, however, soil enzyme activities may not be a good protocol due to their complex response patterns to antimony pollution.

  19. Simultaneous inhibition of acrylamide and hydroxymethylfurfural formation by sodium glutamate microcapsules in an asparagine-glucose model system.

    PubMed

    Wang, Zimeng; Wen, Chao; Shi, Xingbo; Lu, Dai; Deng, Jiehong; Deng, Fangming

    2017-02-01

    Inhibiting the formation of acrylamide (AA) and hydroxymethylfurfural (HMF) during food heating processes has attracted considerable investigative efforts due to potential health concerns associated with these compounds. The main purpose of this work is to demonstrate a strategy to simultaneously inhibit the formation of AA and HMF with sodium glutamate microcapsules selected to confirm the efficacy of this strategy. An asparagine-glucose aqueous model system was prepared containing free sodium glutamate and sodium glutamate microcapsules. Compared to adding free sodium glutamate, the maximum inhibition efficiency for AA and HMF was found to increase by addition of sodium glutamate microcapsules to 19.07 and 84.32%, respectively. Moreover, the kinetics of AA and HMF formation were studied in this model system. The AA inhibition efficiency significantly increased from 6.75 to 60.35% and the HMF inhibition efficiency significantly increased from 5.98 to 79.72% with increasing the reaction time from 25 to 40 min, indicating that the sodium glutamate microcapsules strategy proves to be far superior at prolonged heating times. These findings suggested that this inhibition strategy may provide promising characteristics for a variety of applications in food processing.

  20. Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate.

    PubMed

    Coelho, Deise Riba; Miranda, Elaine Silva; Saint'Pierre, Tatiana Dillenburg; Paumgartten, Francisco José Roma

    2014-07-01

    Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 > 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen > bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies.

  1. Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

    PubMed Central

    Coelho, Deise Riba; Miranda, Elaine Silva; Saint’Pierre, Tatiana Dillenburg; Paumgartten, Francisco José Roma

    2014-01-01

    Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies. PMID:25075781

  2. Sodium caprate augments the hypoglycemic effect of berberine via AMPK in inhibiting hepatic gluconeogenesis.

    PubMed

    Zhang, Ming; Lv, Xiaoyan; Li, Jing; Meng, Zhaojie; Wang, Qiujing; Chang, WenGuang; Li, Wei; Chen, Li; Liu, Yanjun

    2012-11-05

    Berberine (BER), a natural product and active ingredient of genera Berberis and Coptis, has been demonstrated to possess anti-diabetic activities. However, the poor bioavailability of this agent greatly limits its clinical application. In our previous study, we demonstrated that co-administration of sodium caprate, an absorption enhancer, with BER could significantly increase the bioavailability of BER without any serious mucosal damage. Here, we investigated the effects of BER on AMP-activated protein kinase (AMPK)/gluconeogenesis pathway and the effects of sodium caprate on hypoglycemic action of BER. The ability of BER co-administered with sodium caprate to reduce insulin resistance was investigated in diabetic rat model induced by high-fat diet and low dose STZ. Western blot was performed to evaluate effects of BER on AMPK signaling proteins involved in hepatic gluconeogenesis in diabetic rat and HepG2 hepatocytes. BER reduced body weight and caused a significant improvement in glucose tolerance without altering food intake in diabetic rats. Similarly, BER reduced plasma triglycerides and improved insulin action in diabetic rats. BER down-regulated the elevated expressions of gluconeogenesis key enzymes PEPCK and G6Pase, inhibited the translocation of TORC2 from cytoplasm to nucleus and increased AMPK activity in liver tissues. The effect of BER was higher when co-administered with sodium caprate. BER treatment resulted in reduced glucose production in HepG2 hepatocytes. BER increased AMPK activity, reduced the expression of PEPCK, and the nuclear transcription factors PGC-1, HNF-4α and FOXO1. The effect of BER on gluconeogenesis could be partly blocked by AMPK inhibitor, Compound C. BER could suppress hepatic gluconeogenesis in rat model of diabetes at least in part via stimulation of AMPK activity and this action of BER is augmented by sodium caprate.

  3. Jingzhaotoxin-I, a novel spider neurotoxin preferentially inhibiting cardiac sodium channel inactivation.

    PubMed

    Xiao, Yucheng; Tang, Jianzhou; Hu, Weijun; Xie, Jinyun; Maertens, Chantal; Tytgat, Jan; Liang, Songping

    2005-04-01

    Jingzhaotoxin-I (JZTX-I), a 33-residue polypeptide, is derived from the Chinese tarantula Chilobrachys jing-zhao venom based on its ability to evidently increase the strength and the rate of vertebrate heartbeats. The toxin has three disulfide bonds with the linkage of I-IV, II-V, and III-VI that is a typical pattern found in inhibitor cystine knot molecules. Its cDNA determined by rapid amplification of 3'- and 5'-cDNA ends encoded a 62-residue precursor with a small proregion of eight residues. Whole-cell configuration indicated that JZTX-I was a novel neurotoxin preferentially inhibiting cardiac sodium channel inactivation by binding to receptor site 3. Although JZTX-I also exhibits the interaction with channel isoforms expressing in mammalian and insect sensory neurons, its affinity for tetrodotoxin-resistant subtype in mammalian cardiac myocytes (IC50 = 31.6 nm) is approximately 30-fold higher than that for tetrodotoxin-sensitive subtypes in latter tissues. Not affecting outward delay-rectified potassium channels expressed in Xenopus laevis oocytes and tetrodotoxin-resistant sodium channels in mammal sensory neurons, JZTX-I hopefully represents a potent ligand to discriminate cardiac sodium channels from neuronal tetrodotoxin-resistant isoforms. Furthermore, different from any reported spider toxins, the toxin neither modifies the current-voltage relationships nor shifts the steady-state inactivation of sodium channels. Therefore, JZTX-I defines a new subclass of spider sodium channel toxins. JZTX-I is an alpha-like toxin first reported from spider venoms. The result provides an important witness for a convergent functional evolution between spider and other animal venoms.

  4. Inhibition of sodium current by taurine magnesium coordination compound prevents cesium chloride-induced arrhythmias.

    PubMed

    Yin, Yongqiang; Wen, Ke; Wu, Yanna; Kang, Yi; Lou, Jianshi

    2012-05-01

    The mechanism(s) by which taurine magnesium coordination compound (TMCC) inhibits experimental arrhythmias remains poorly understood. The purpose of this study was to observe the effects of TMCC against cesium chloride-induced arrhythmia in the rabbit heart and find whether the antiarrhythmic activity is related to inhibition of sodium current. Early afterdepolarization was induced by 1.5 mM cesium chloride (1 ml kg(-1)) through intravenous injection. The monophasic action potentials (MAP) and electrocardiograms were simultaneously recorded. The effect of TMCC on functional refractory periods (FRPs) in the left atrium was also observed in vitro. Arrhythmias onset was significantly retarded by TMCC. The number of ventricular premature contractions and incidence of monophasic ventricular tachycardia and polyphasic ventricular tachycardia in 10 min were decreased by TMCC. These effects can be abolished by veratridine (10 μg kg(-1)). MAP duration at 90% repolarization was significantly prolonged by TMCC, which can be prolonged even longer by veratridine (10 μg kg(-1)). In vitro experiments showed that FRPs was prolonged by TMCC which can be cancelled by veratridine (10 μg kg(-1)). TMCC prevents cesium chloride-induced arrhythmias, and inhibition of sodium current, in part, contributes to the antiarrhythmic effect of TMCC.

  5. Corrosion inhibition of rapidly solidified Mg-3% Zn-15% Al magnesium alloy with sodium carboxylates

    SciTech Connect

    Daloz, D.; Michot, G.; Rapin, C.; Steinmetz, P.

    1998-06-01

    The ability of sodium linear-saturated carboxylates to protect magnesium alloys against aqueous corrosion was characterized. Electrochemical measurements of polarization resistance and corrosion current showed the inhibition efficiency of these compounds is a function of their concentration and of the length of the aliphatic chain. In every case studied, the efficiency increased with immersion time. At pH 8, the best inhibiting behavior was observed with 0.05 M sodium undecanoate. The potential-pH diagram of magnesium in an aqueous solution containing undecanoate anions was generated based upon the solubility determined for magnesium undecanoate (Mg[CH{sub 3}(CH{sub 2}){sub 9}COO]{sub 2}). According to this diagram, the very low corrosion rate was suspected to result from formation of Mg(CH{sub 3}[CH{sub 2}]{sub 9}COO){sub 2}. Infrared spectrometry carried out on both the synthesized magnesium carboxylate and the product from the magnesium alloy surface after inhibitive treatment confirmed this hypothesis.

  6. Dual effectiveness of sodium chlorite for enzymatic browning inhibition and Escherichia coli inactivation on fresh-cut apples

    USDA-ARS?s Scientific Manuscript database

    This study investigated the dual effectiveness of sodium chlorite (SC) for browning inhibition and microbial inactivation on fresh-cut apples. The SC treatment exhibited a strong inhibition on browning reaction of fresh-cut Red Delicious apples during cold storage. Test results from examination of t...

  7. Ferrous iron oxidation by Thiobacillus ferrooxidans: inhibition with benzoic acid, sorbic acid and sodium lauryl sulfate

    SciTech Connect

    Onysko, S.J.

    1984-07-01

    Acid mine drainage is formed by the weathering or oxidation of pyritic material exposed during coal mining. The rate of pyritic material oxidation can be greatly accelerated by certain acidophilic bacteria such as Thiobacillus ferrooxidans which catalyse the oxidation of ferrous to ferric iron. A number of organic compounds, under laboratory conditions, can apparently inhibit both the oxidation of ferrous to ferric iron by T. ferrooxidans and the weathering of pyritic material by mixed cultures of acid mine drainage micro-organisms. Sodium lauryl sulphate (SLS), an anionic surfactant has proved effective in this respect. Benzoic acid, sorbic acid and SLS at low concentrations, each effectively inhibited bacterial oxidation of ferrous iron in batch cultures of T. ferrooxidans. The rate of chemical oxidation of ferrous iron in low pH, sterile, batch reactors was not substantially affected at the tested concentrations of any of the compounds.

  8. Plant-Derived Polysaccharide Supplements Inhibit Dextran Sulfate Sodium-Induced Colitis in the Rat

    PubMed Central

    Koetzner, Lee; Grover, Gary; Boulet, Jamie

    2009-01-01

    Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count. PMID:19513840

  9. Plant-derived polysaccharide supplements inhibit dextran sulfate sodium-induced colitis in the rat.

    PubMed

    Koetzner, Lee; Grover, Gary; Boulet, Jamie; Jacoby, Henry I

    2010-05-01

    Several plant-derived polysaccharides have been shown to have anti-inflammatory activity in animal models. Ambrotose complex and Advanced Ambrotose are dietary supplements that include aloe vera gel, arabinogalactan, fucoidan, and rice starch, all of which have shown such activity. This study was designed to evaluate these formulations against dextran sulfate sodium (DSS)-induced colitis in rats and to confirm their short-term safety after 14 days of daily dosing. Rats were dosed daily orally with vehicle, Ambrotose or Advanced Ambrotose. On day six groups of rats received tap water or 5% Dextran Sulfate sodium. Ambrotose and Advanced Ambrotose significantly lowered the disease scores and partially prevented the shortening of colon length. An increase in monocyte count was induced by dextran sulfate sodium and inhibited by Ambrotose and Advanced Ambrotose. There were no observable adverse effects after 14-day daily doses. The mechanism of action of the formulations against DSS-induced colitis may be related to its effect on monocyte count.

  10. Inhibition of ATPase activity in the freshwater fish Labeo rohita (Hamilton) exposed to sodium cyanide.

    PubMed

    Dube, Praveen N; Hosetti, Basaling B

    2011-10-01

    Present study concerns the effect of sodium cyanide on the Indian major carp, Labeo rohita. Fishes were exposed to lethal (0.32 mg/L) and sublethal (0.064 mg/L) concentrations of sodium cyanide. The effect of intoxication was studied on Na(+)K(+)ATPase, Mg(+2)ATPase and Ca(2+)ATPase in various physiological tissues (gill, liver, and muscle) at the end of 1, 2, 3 and 4 days of lethal and 5, 10 and 15 days of sublethal exposure periods. Sodium cyanide induced significant inhibitory effects on the ATPase activity of the fish. Inhibition of the ATPase blocked the active transport system of the gill epithelial as well as chloride cells, and thus altered the osmo-regulatory mechanism of the fish. The value of the measured responses as an indicator of stress caused by water contamination discussed. The results confirm that ATPase levels significantly decreased in treated fish, indicating that ATPases could be used as sensitive and useful biomarkers for cyanide pollution.

  11. Cell volume changes upon sodium pump inhibition in Helix aspersa neurones.

    PubMed Central

    Alvarez-Leefmans, F J; Gamiño, S M; Reuss, L

    1992-01-01

    1. Identified neurones of the suboesophageal ganglia of Helix aspersa were loaded with tetramethylammonium (TMA+). Experimentally induced changes in cell water volume and membrane potential were measured continuously by monitoring changes in intracellular [TMA+] using ion-sensitive double-barrelled microelectrodes. The technique allowed measurements of cell water volume changes of less than 5%. 2. Exposure to hyperosmotic (up to +24%) or hyposmotic (up to about -10%) solutions caused reversible decreases and increases in cell water volume respectively, which agreed with near-ideal osmometric behaviour. Upon exposure to hyposmotic solutions whose osmolality was decreased by 30-40%, the cell water volume increased to maximum values below those expected for ideal osmometric behaviour and exhibited partial regulatory volume decrease. 3. The sodium pump was inhibited in twenty identified neurones by sustained exposure to 1 mM ouabain. In every case ouabain caused cell membrane depolarization, as expected for inhibition of an electrogenic sodium pump. 4. Upon pump inhibition most cells (n = 14) shrank by up to 13% of their initial water volume. In five of these cells, shrinkage was preceded by one or more short-lived swelling phases. In two other neurones short-lived swelling was followed by cell volume recovery without appreciable shrinkage. In four out of the twenty cells, there were no measurable volume changes. 5. The lack of an initial swelling phase in the cells that shrank, as well as the absence of detectable volume changes in some of the neurones, was not due to loss of ion-selective electrode sensitivity since predictable changes in cell volume elicited by osmotic challenges were monitored in the same cells. 6. It is concluded that neurones can be endowed with ouabain-insensitive mechanisms of volume control, whose activation following Na+ pump inhibition prevents them from short-term swelling and lysis. PMID:1338793

  12. Inhibition of Protease-Epithelial Sodium Channel Signaling Improves Mucociliary Function in Cystic Fibrosis Airways.

    PubMed

    Reihill, James A; Walker, Brian; Hamilton, Robert A; Ferguson, Timothy E G; Elborn, J Stuart; Stutts, M Jackson; Harvey, Brian J; Saint-Criq, Vinciane; Hendrick, Siobhan M; Martin, S Lorraine

    2016-09-15

    In cystic fibrosis (CF) a reduction in airway surface liquid (ASL) height compromises mucociliary clearance, favoring mucus plugging and chronic bacterial infection. Inhibitors of the epithelial sodium channel (ENaC) have therapeutic potential in CF airways to reduce hyperstimulated sodium and fluid absorption to levels that can restore airway hydration. To determine whether a novel compound (QUB-TL1) designed to inhibit protease/ENaC signaling in CF airways restores ASL volume and mucociliary function. Protease activity was measured using fluorogenic activity assays. Differentiated primary airway epithelial cell cultures (F508del homozygotes) were used to determined ENaC activity (Ussing chamber recordings), ASL height (confocal microscopy), and mucociliary function (by tracking the surface flow of apically applied microbeads). Cell toxicity was measured using a lactate dehydrogenase assay. QUB-TL1 inhibits extracellularly located channel activating proteases (CAPs), including prostasin, matriptase, and furin, the activities of which are observed at excessive levels at the apical surface of CF airway epithelial cells. QUB-TL1-mediated CAP inhibition results in diminished ENaC-mediated Na(+) absorption in CF airway epithelial cells caused by internalization of a prominent pool of cleaved (active) ENaCγ from the cell surface. Importantly, diminished ENaC activity correlates with improved airway hydration status and mucociliary clearance. We further demonstrate QUB-TL1-mediated furin inhibition, which is in contrast to other serine protease inhibitors (camostat mesylate and aprotinin), affords protection against neutrophil elastase-mediated ENaC activation and Pseudomonas aeruginosa exotoxin A-induced cell death. QUB-TL1 corrects aberrant CAP activities, providing a mechanism to delay or prevent the development of CF lung disease in a manner independent of CF transmembrane conductance regulator mutation.

  13. Neurosteroid dehydroepiandrosterone sulphate inhibits persistent sodium currents in rat medial prefrontal cortex via activation of sigma-1 receptors.

    PubMed

    Cheng, Zheng-Xiang; Lan, Dan-Mei; Wu, Pei-Ying; Zhu, Yan-Hua; Dong, Yi; Ma, Lan; Zheng, Ping

    2008-03-01

    Dehydroepiandrosterone sulphate is one of the most important neurosteroids. In the present paper, we studied the effect of dehydroepiandrosterone sulphate on persistent sodium currents and its mechanism and functional consequence with whole-cell patch clamp recording method combined with a pharmacological approach in the rat medial prefrontal cortex slices. The results showed that dehydroepiandrosterone sulphate inhibited the amplitude of persistent sodium currents and the inhibitory effect was significant at 0.1 microM, reached maximum at 1 microM and decreased with the increase in the concentrations of above 1 microM. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was canceled by the Gi protein inhibitor and the protein kinase C inhibitor, but not by the protein kinase A inhibitor. The effect of dehydroepiandrosterone sulphate on persistent sodium currents was also canceled by the sigma-1 receptor blockers and the sigma-1 receptor agonist could mimic the effect of dehydroepiandrosterone sulphate. Dehydroepiandrosterone sulphate had no significant influence on neuronal excitability but could significantly inhibit chemical inhibition of mitochondria-evoked increase in persistent sodium currents. These results suggest that dehydroepiandrosterone sulphate inhibits persistent sodium currents via the activation of sigma-1 receptors-Gi protein-protein kinase C-coupled signaling pathway, and the main functional consequence of this effect of DHEAS is presumably to protect neurons under ischemia.

  14. How Sodium Chloride Salt Inhibits the Formation of CO2 Gas Hydrates.

    PubMed

    Holzammer, Christine; Finckenstein, Agnes; Will, Stefan; Braeuer, Andreas S

    2016-03-10

    We present an experimental Raman study on how the addition of sodium chloride to CO2-hydrate-forming systems inhibits the hydrate formation thermodynamically. For this purpose, the molar enthalpy of reaction and the molar entropy of reaction for the reaction of weakly hydrogen-bonded water molecules to strongly hydrogen bonded water molecules are determined for different salinities from the Raman spectrum of the water-stretching vibration. Simultaneously, the influence of the salinity on the solubility of CO2 in the liquid water-rich phase right before the start of hydrate formation is analyzed. The results demonstrate that various mechanisms contribute to the inhibition of gas hydrate formation. For the highest salt concentration of 20 wt % investigated, the temperature of gas hydrate formation is lowered by 12 K. For this concentration the molar enthalpy and entropy of reaction become smaller by 50 and 20%, respectively. Concurrently, the solubility of carbon dioxide is reduced by 70%. These results are compared with data in literature for systems of sodium chloride in water (without carbon dioxide).

  15. Effective inhibition of mannitol crystallization in frozen solutions by sodium chloride.

    PubMed

    Telang, Chitra; Yu, Lian; Suryanarayanan, Raj

    2003-04-01

    The purpose of this work was to study the possibility of preventing mannitol crystallization in frozen solutions by using pharmaceutically acceptable additives. Differential scanning calorimetry (DSC) and low-temperature X-ray diffractometry (LTXRD) were used to characterize the effect of additives on mannitol crystallization. DSC screening revealed that salts (sodium chloride, sodium citrate, and sodium acetate) inhibited mannitol crystallization in frozen solutions more effectively than selected surfactants, alpha-cyclodextrin, polymers, and alditols. This finding prompted further studies of the crystallization in the mannitol-NaCl-water system. Isothermal DSC results indicated that mannitol crystallization in frozen solutions was significantly retarded in the presence of NaCl and that NaCl did not crystallize until mannitol crystallization completed. Low-temperature X-ray diffractometry data showed that when a 10% w/v mannitol solution without additive was cooled at 1 degrees C/min, the crystalline phases emerging after ice crystallization were those of a mannitol hydrate as well as the anhydrous polymorphs. In the presence of NaCl (5% w/v), mannitol crystallization was suppressed during both cooling and warming and occurred only after annealing and rewarming. In the latter case however, mannitol did not crystallize as the hydrate, but as the anhydrous delta polymorph. At a lower NaCl concentration of 1% w/v, the inhibitory effect of NaCl on mannitol crystallization was evident even during annealing at temperatures close to the Tg' (-40 degrees C). A preliminary lyophilization cycle with polyvinyl pyrrolidone and NaCl as additives rendered mannitol amorphous. The effectiveness of additives in inhibiting mannitol crystallization in frozen solutions follows the general order: salts > alditols > polyvinyl pyrrolidone > alpha-cyclodextrin > polysorbate 80 approximately polyethylene glycol approximately poloxamer. The judicious use of additives can retain mannitol

  16. Energy balance and metabolic changes with sodium-glucose co-transporter 2 inhibition.

    PubMed

    Rajeev, S P; Cuthbertson, D J; Wilding, J P H

    2016-02-01

    Sodium-glucose co-transporter 2 (SGLT2) inhibitors are the latest addition to the class of oral glucose-lowering drugs. They have been rapidly adopted into clinical practice because of therapeutic advantages, including weight loss and reduction in blood pressure, in addition to glycaemic benefits and a low intrinsic risk of hypoglycaemia. Although there are extensive data on the clinical effects of SGLT2 inhibition, the metabolic effects of inhibiting renal glucose reabsorption have not been fully described. Recent studies have identified compensatory metabolic effects, such as an increase in endogenous glucose production, and have also shown an increase in glucagon secretion during SGLT2 inhibition. In addition, there is a discrepancy between the expected and observed weight loss found in clinical studies on SGLT2 inhibitors, probably as a result of changes in energy balance with this treatment approach. SGLT2 inhibition is likely to have intriguing effects on whole body metabolism which have not been fully elucidated, and which, if explained, might help optimize the use of this new class of medicines. © 2015 John Wiley & Sons Ltd.

  17. Increased renal sodium absorption by inhibition of prostaglandin synthesis during fasting in healthy man. A possible role of the epithelial sodium channels

    PubMed Central

    2010-01-01

    Background Treatment with prostaglandin inhibitors can reduce renal function and impair renal water and sodium excretion. We tested the hypotheses that a reduction in prostaglandin synthesis by ibuprofen treatment during fasting decreased renal water and sodium excretion by increased absorption of water and sodium via the aquaporin2 water channels and the epithelial sodium channels. Methods The effect of ibuprofen, 600 mg thrice daily, was measured during fasting in a randomized, placebo-controlled, double-blinded crossover study of 17 healthy humans. The subjects received a standardized diet on day 1, fasted at day 2, and received an IV infusion of 3% NaCl on day 3. The effect variables were urinary excretions of aquaporin2 (u-AQP2), the beta-fraction of the epithelial sodium channel (u-ENaCbeta), cyclic-AMP (u-cAMP), prostaglandin E2 (u-PGE2). Free water clearance (CH2O), fractional excretion of sodium (FENa), and plasma concentrations of vasopressin, angiotensin II, aldosterone, atrial-, and brain natriuretic peptide. Results Ibuprofen decreased u-AQP2, u-PGE2, and FENa at all parts of the study. During the same time, ibuprofen significantly increased u-ENaCbeta. Ibuprofen did not change the response in p-AVP, u-c-AMP, urinary output, and free water clearance during any of these periods. Atrial-and brain natriuretic peptide were higher. Conclusion During inhibition of prostaglandin synthesis, urinary sodium excretion decreased in parallel with an increase in sodium absorption and increase in u-ENaCbeta. U-AQP2 decreased indicating that water transport via AQP2 fell. The vasopressin-c-AMP-axis did not mediate this effect, but it may be a consequence of the changes in the natriuretic peptide system and/or the angiotensin-aldosterone system Trial Registration Clinical Trials Identifier: NCT00281762 PMID:21029429

  18. Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: the emerging role of natriuresis.

    PubMed

    Rajasekeran, Harindra; Lytvyn, Yuliya; Cherney, David Z I

    2016-03-01

    Inhibition of sodium-glucose cotransporter 2 causes both glycosuria and natriuresis, leading to reductions in hyperglycemia, body weight, blood pressure, and proteinuria. The recently published EMPA-REG OUTCOME study demonstrated significant cardiovascular and mortality benefits of sodium-glucose cotransporter 2 inhibition with empagliflozin in patients with type 2 diabetes and established cardiovascular disease, and may suggest a broader role for sodium-glucose cotransporter 2 inhibition in patients with heart failure.

  19. Pilot testing of sodium thiosulfate for oxidation/scaling inhibition in lime/limestone flue gas desulfurization systems

    SciTech Connect

    Chang, J.C.S.; Brna, T.G.

    1985-01-01

    Pilot plant tests have been conducted to evaluate sodium thiosulfate as an oxidation inhibition additive in five lime/limestone slurry flue gas desulfurization processes. It was found that the oxidation rate of absorbed sulfur dioxide (SO/sub 2/) was reduced by more than 50 percent in the presence of 100 to 200 ppm of thiosulfate ion in the scrubbing slurry. Calcium sulfate dihydrate (gypsum) scaling was eliminated and the unsaturated (with respect to gypsum) operation mode was maintained by the addition of sodium thiosulfate. Other benefits of sodium thiosulfate addition observed at the pilot plant included improvement in solids dewatering properties for limestone processes.

  20. A novel μ-conotoxin from worm-hunting Conus tessulatus that selectively inhibit rat TTX-resistant sodium currents.

    PubMed

    Yang, Manyi; Zhao, Shuang; Min, Xiaoli; Shao, Meiying; Chen, Yongheng; Chen, Zhuchu; Zhou, Maojun

    2017-05-01

    μ-conotoxins are a group of marine Conus peptides that inhibit sodium currents, so μ-conotoxins are valuable in sodium channel research and new analgesic drug discovery. Here, a novel μ-conotoxin TsIIIA was identified from a worm-hunting Conus tessulatus. TsIIIA was chemical synthesized according to its amino acid sequence GCCRWPCPSRCGMARCCSS and identified by mass spectrum. Patch clamp on rat dorsal root ganglion cells showed that 10 μM TsIIIA specifically inhibit TTX-resistant sodium currents but has no effect on TTX-sensitive sodium currents. TsIIIA inhibits TTX-resistant sodium currents by a dose-dependent mode with an IC50 of 2.61 μM. Further study showed 10 μM TsIIIA has no obvious effect on the current-voltage relationships, conductance-voltage relationships and voltage-dependence of steady-state inactivation of TTX-resistant sodium channels. Mice hotplate analgesic assay indicated that TsIIIA obviously increase the pain threshold at 0.5-4 h. In addition, TsIIIA has better analgesic effects than Ziconotide, indicating that TsIIIA was a valuable lead compound for development of new analgesic drug. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Classification of Drugs Based on Properties of Sodium Channel Inhibition: A Comparative Automated Patch-Clamp Study

    PubMed Central

    Lenkey, Nora; Karoly, Robert; Lukacs, Peter; Vizi, E. Sylvester; Sunesen, Morten; Fodor, Laszlo; Mike, Arpad

    2010-01-01

    Background There is only one established drug binding site on sodium channels. However, drug binding of sodium channels shows extreme promiscuity: ∼25% of investigated drugs have been found to potently inhibit sodium channels. The structural diversity of these molecules suggests that they may not share the binding site, and/or the mode of action. Our goal was to attempt classification of sodium channel inhibitors by measuring multiple properties of inhibition in electrophysiology experiments. We also aimed to investigate if different properties of inhibition correlate with specific chemical properties of the compounds. Methodology/Principal Findings A comparative electrophysiological study of 35 compounds, including classic sodium channel inhibitors (anticonvulsants, antiarrhythmics and local anesthetics), as well as antidepressants, antipsychotics and neuroprotective agents, was carried out using rNav1.2 expressing HEK-293 cells and the QPatch automatic patch-clamp instrument. In the multi-dimensional space defined by the eight properties of inhibition (resting and inactivated affinity, potency, reversibility, time constants of onset and offset, use-dependence and state-dependence), at least three distinct types of inhibition could be identified; these probably reflect distinct modes of action. The compounds were clustered similarly in the multi-dimensional space defined by relevant chemical properties, including measures of lipophilicity, aromaticity, molecular size, polarity and electric charge. Drugs of the same therapeutic indication typically belonged to the same type. We identified chemical properties, which were important in determining specific properties of inhibition. State-dependence correlated with lipophilicity, the ratio of the neutral form of molecules, and aromaticity: We noticed that the highly state dependent inhibitors had at least two aromatic rings, logP>4.0, and pKa<8.0. Conclusions/Significance The correlations of inhibition properties

  2. Kinetic analysis of phasic inhibition of neuronal sodium currents by lidocaine and bupivacaine.

    PubMed Central

    Chernoff, D M

    1990-01-01

    Phasic ("use-dependent") inhibition of sodium currents by the tertiary amine local anesthetics, lidocaine and bupivacaine, was observed in voltage-clamped node of Ranvier of the toad, Bufo marinus. Local anesthetics were assumed to inhibit sodium channels through occupation of a binding site with 1:1 stoichiometry. A three-parameter empirical model for state-dependent anesthetic binding to the Na channel is presented: this model includes two discrete parameters that represent the time integrals of binding and unbinding reactions during a depolarizing pulse, and one continuous parameter that represents the rate of unbinding of drug between pulses. The change in magnitude of peak sodium current during a train of depolarizing pulses to 0 mV was used as an assay of the extent of anesthetic binding at discrete intervals; estimates of model parameters were made by applying a nonlinear least-squares algorithm to the inhibition of currents obtained at two or more depolarizing pulse rates. Increasing the concentration of drug increased the rate of binding but had little or no effect on unbinding, as expected for a simple bimolecular reaction. The dependence of the model parameters on pulse duration was assessed for both drugs: as the duration of depolarizing pulses was increased, the fraction of channels binding drug during each pulse became significantly larger, whereas the fraction of occupied channels unbinding drug remained relatively constant. The rate of recovery from block between pulses was unaffected by pulse duration or magnitude. The separate contributions of open (O) and inactivated (I) channel binding of drug to the net increase in block per pulse were assessed at 0 mV: for lidocaine, the forward binding rate ko was 1.3 x 10(5) M-1 s-1, kl was 2.4 x 10(4) M-1 s-1; for bupivacaine, ko was 2.5 x 10(5) M-1 s-1, kl was 4.4 x 10(4) M-1 s-1. These binding rates were similar to those derived from time-dependent block of maintained Na currents in nodes where

  3. Computational models for drug inhibition of the human apical sodium-dependent bile acid transporter.

    PubMed

    Zheng, Xiaowan; Ekins, Sean; Raufman, Jean-Pierre; Polli, James E

    2009-01-01

    The human apical sodium-dependent bile acid transporter (ASBT; SLC10A2) is the primary mechanism for intestinal bile acid reabsorption. In the colon, secondary bile acids increase the risk of cancer. Therefore, drugs that inhibit ASBT have the potential to increase the risk of colon cancer. The objectives of this study were to identify FDA-approved drugs that inhibit ASBT and to derive computational models for ASBT inhibition. Inhibition was evaluated using ASBT-MDCK monolayers and taurocholate as the model substrate. Computational modeling employed a HipHop qualitative approach, a Hypogen quantitative approach, and a modified Laplacian Bayesian modeling method using 2D descriptors. Initially, 30 compounds were screened for ASBT inhibition. A qualitative pharmacophore was developed using the most potent 11 compounds and applied to search a drug database, yielding 58 hits. Additional compounds were tested, and their K(i) values were measured. A 3D-QSAR and a Bayesian model were developed using 38 molecules. The quantitative pharmacophore consisted of one hydrogen bond acceptor, three hydrophobic features, and five excluded volumes. Each model was further validated with two external test sets of 30 and 19 molecules. Validation analysis showed both models exhibited good predictability in determining whether a drug is a potent or nonpotent ASBT inhibitor. The Bayesian model correctly ranked the most active compounds. In summary, using a combined in vitro and computational approach, we found that many FDA-approved drugs from diverse classes, such as the dihydropyridine calcium channel blockers and HMG CoA-reductase inhibitors, are ASBT inhibitors.

  4. Computational Models for Drug Inhibition of the Human Apical Sodium-dependent Bile Acid Transporter

    PubMed Central

    Zheng, Xiaowan; Ekins, Sean; Raufman, Jean-Pierre; Polli, James E.

    2009-01-01

    The human apical sodium-dependent bile acid transporter (ASBT; SLC10A2) is the primary mechanism for intestinal bile acid re-absorption. In the colon, secondary bile acids increase the risk of cancer. Therefore, drugs that inhibit ASBT have the potential to increase the risk of colon cancer. The objectives of this study were to identify FDA-approved drugs that inhibit ASBT and to derive computational models for ASBT inhibition. Inhibition was evaluated using ASBT-MDCK monolayers and taurocholate as the model substrate. Computational modeling employed a HipHop qualitative approach, a Hypogen quantitative approach, as well as a modified Laplacian Bayesian modeling method using 2D descriptors. Initially, 30 compounds were screened for ASBT inhibition. A qualitative pharmacophore was developed using the most potent 11 compounds and applied to search a drug database, yielding 58 hits. Additional compounds were tested and their Ki values were measured. A 3D-QSAR and a Bayesian model were developed using 38 molecules. The quantitative pharmacophore consisted of one hydrogen bond acceptor, three hydrophobic features, and five excluded volumes. Each model was further validated with two external test sets of 30 and 19 molecules. Validation analysis showed both models exhibited good predictability in determining whether a drug is a potent or non-potent ASBT inhibitor. The Bayesian model correctly ranked the most active compounds. In summary, using a combined in vitro and computational approach, we found that many FDA-approved drugs from diverse classes, such as the dihydropyridine calcium channel blockers and HMG CoA-reductase inhibitors, are ASBT inhibitors. PMID:19673539

  5. Influence of Antimony-Halogen Additives on Flame Propagation.

    PubMed

    Babushok, Valeri I; Deglmann, Peter; Krämer, Roland; Linteris, Gregory T

    2017-01-01

    A kinetic model for flame inhibition by antimony-halogen compounds in hydrocarbon flames is developed. Thermodynamic data for the relevant species are assembled from the literature, and calculations are performed for a large set of additional species of Sb-Br-C-H-O system. The main Sb- and Br-containing species in the combustion products and reaction zone are determined using flame equilibrium calculations with a set of possible Sb-Br-C-H-O species, and these are used to develop the species and reactions in a detailed kinetic model for antimony flame inhibition. The complete thermodynamic data set and kinetic mechanism are presented. Laminar burning velocity simulations are used to validate the mechanism against available data in the literature, as well as to explore the relative performance of the antimony-halogen compounds. Further analysis of the premixed flame simulations has unraveled the catalytic radical recombination cycle of antimony. It includes (primarily) the species Sb, SbO, SbO2, and HOSbO, and the reactions: Sb+O+M=SbO+M; Sb+O2+M=SbO2+M; SbO+H=Sb+OH; SbO+O=Sb+O2; SbO+OH+M=HOSbO+M; SbO2+H2O=HOSbO+OH; HOSbO+H=SbO+H2O; SbO+O+M=SbO2+M. The inhibition cycles of antimony are shown to be more effective than those of bromine, and intermediate between the highly effective agents CF3Br and trimethylphosphate. Preliminary examination of a Sb/Br gas-phase system did not show synergism in the gas-phase catalytic cycles (i.e., they acted essentially independently).

  6. Antimony activities in copper mattes

    NASA Astrophysics Data System (ADS)

    Hino, M.; Toguri, J. M.

    1987-03-01

    A mass spectrometric technique combined with a double Knudsen cell was used to determine the antimony and copper activities in the Cu-Sb binary system at 1373 K and in the two-melt composition range of the Cu-S-Sb ternary system at 1423 K. The antimony and copper activities were calculated based on the intensity ration of the gaseous Sb and Cu species, over the unknown and known activity samples, respectively. γ{Sb/o} were found to be 1.1×10-2 in molten copper at 1373 K, and 1.8×10-2 and 0.44 in a copper-rich phase and in a matter phase, of the Cu-S-Sb ternary system at 1423 K, respectively. These values indicate, that antimony can be removed during the matte smelting and slagging stage of the copper smelting process. Interaction parameters of antimony in molten copper slagging stage of the copper smelting process. Interaction parameters of antimony in molten copper at 1423 K were calculated and found to be 10.7, -5.4, and 6.3 for ɛ{Sb/Sb} · ρSb Sb, and ɛ{Sb/S}, respectively.

  7. Hydrometallurgically treating antimony-bearing industrial wastes

    NASA Astrophysics Data System (ADS)

    Anderson, C. G.

    2001-01-01

    In many instances, by-products or wastes containing antimony are generated during metallurgical processes. Although these materials pose environmental, recycling, and marketing challenges worldwide, the use of antimony hydrometallurgical leaching principles and technologies may provide a remedy. This paper outlines techniques for treating antimony-containing wastes and offers examples of applications for those wastes and by-products.

  8. Sodium Methyldithiocarbamate Exerts Broad Inhibition of Cellular Signaling and Expression of Effector Molecules of Inflammation

    PubMed Central

    Pruett, Stephen B.

    2013-01-01

    Sodium methyldithiocarbamate (SMD) is one of the most abundantly used conventional pesticides in the United States. At dosages relevant to occupational exposure, it causes major effects on the immune system in mice, including a decreased resistance to sepsis. This lab has identified some of the mechanisms of action of this compound and some of the immunological parameters affected, but the global effects have not previously been assessed. The purpose of the present study was to conduct transcriptomic analysis of the effects of SMD on lipopolysaccharide-induced expression of mediators important in innate immunity and inflammation. The results revealed broad effects on expression of transcription factors in both branches of Toll-like receptor 4 (TLR4) signaling (MyD88 and TRIF). However, TLR3 and interferon signaling pathways were decreased to a greater extent, and assessment of the effects of SMD on polyinosinic polycytidylic acid–induced cytokine and chemokine production revealed that these responses mediated by TLR3 were indeed sensitive to the effects of SMD, with inhibition occurring at lower dosages than required to inhibit responses to other immunological stimuli tested in our previous studies. In the downstream signaling pathways of these TLRs, functional analysis also revealed that NF-κB activation was inhibited by SMD, as indicated by gene expression analysis and a reporter construct in mice. A previously unreported effect on luteinizing hormone and follicle-stimulating hormone pathways was also observed. PMID:24056979

  9. Selective inhibition of sweetness by the sodium salt of +/-2-(4-methoxyphenoxy)propanoic acid.

    PubMed

    Schiffman, S S; Booth, B J; Sattely-Miller, E A; Graham, B G; Gibes, K M

    1999-08-01

    The purpose of this study was to determine the degree to which the sodium salt of +/-2-(4-methoxyphenoxy)propanoic acid (Na-PMP) reduced sweet intensity ratings of 15 sweeteners in mixtures. Na-PMP has been approved for use in confectionary/frostings, soft candy and snack products in the USA at concentrations up to 150 p.p.m. A trained panel evaluated the effect of Na-PMP on the intensity of the following 15 sweeteners: three sugars (fructose, glucose, sucrose), three terpenoid glycosides (monoammonium glycyrrhizinate, rebaudioside-A, stevioside), two dipeptide derivatives (alitame, aspartame), two N-sulfonylamides (acesulfame-K, sodium saccharin), two polyhydric alcohols (mannitol, sorbitol), 1 dihydrochalcone (neohesperidin dihydrochalcone), one protein (thaumatin) and one sulfamate (sodium cyclamate). Sweeteners were tested at concentrations isosweet with 2.5, 5, 7.5 and 10% sucrose in mixtures with two levels of Na-PMP: 250 and 500 p.p.m. In addition, the 15 sweeteners were tested either immediately or 30 s after a pre-rinse with 500 p.p.m. Na-PMP. In mixtures, Na-PMP at both the 250 and 500 p.p.m. levels significantly blocked sweetness intensity for 12 of the 15 sweeteners. However, when Na-PMP was mixed with three of the 15 sweeteners (monoammonium glycyrrhizinate, neohesperidin dihydrochalcone and thaumatin), there was little reduction in sweetness intensity. Pre-rinsing with Na-PMP both inhibited and enhanced sweetness with the greatest enhancements found for monoammonium glycyrrhizinate, neohesperidin dihydrochalcone and thaumatin, which were not suppressed by Na-PMP in mixtures. The mixture data suggest that Na-PMP is a selective competitive inhibitor of sweet taste. The finding that pre-treatment can produce enhancement may be due to sensitization of sweetener receptors by Na-PMP.

  10. Central lead administration inhibits water intake and sodium appetite in rats.

    PubMed

    De-Castro-e-Silva, E J; Castro, L; Luz, C P; Ferreira, H; Lima, A K; Souza, F S; Maldonado, I; Macêdo, D F; Ferreira, M G; Bandeira, I P; Amor, A L; Carvalho, F L; Rocha, M A; Fregoneze, J B

    1999-10-01

    We have demonstrated that acute third ventricle injections of lead acetate (PbAc) exert a powerful antidipsogenic effect and induce a significant increase in renal sodium excretion. In the present study we confirm the antidipsogenic effect of lead and demonstrate that central administration of this metal, in minute amounts, significantly reduces salt intake both during dehydration and after central angiotensinergic stimulation. Adult male Wistar rats had the third ventricle cannulated seven days before the experiments. During this period they had free access to distilled water and hypertonic saline solution (1.5%). After a 24-h period of fluid deprivation, experimental animals received third ventricle injections of PbAc (0.3, N = 8 and 3.0 nmol/rat, N = 14) while controls received sodium acetate (NaAc; 3.0 nmol/rat, N = 10). Rats treated with PbAc at the highest dose showed a significant reduction (P<0.05) both in water and hypertonic saline intake when compared to controls. When the effect of lead administration on angiotensin II-induced water and salt intake was studied, normohydrated animals received third ventricle injections of angiotensin II (9.6 nmol/rat) after pretreatment with 3.0 nmol/rat of PbAc (experimental group, N = 10) or NaAc (controls, N = 8). The group pretreated with PbAc presented a significant reduction (P<0.05) in both water and salt intake compared to controls. Thus, this study confirms the antidipsogenic effect of central lead injections and demonstrates that the presence of lead in the brain exerts a significant inhibition of sodium appetite.

  11. Cooked Chickpea Consumption Inhibits Colon Carcinogenesis in Mice Induced with Azoxymethane and Dextran Sulfate Sodium.

    PubMed

    Chino, Xariss M Sánchez; Martínez, Cristian Jiménez; Garzón, Verónica R Vásquez; González, Isela Álvarez; Treviño, Saúl Villa; Bujaidar, Eduardo Madrigal; Ortiz, Gloria Dávila; Hoyos, Rafael Baltiérrez

    2017-07-01

    The objective of the study was to evaluate the effect of daily consumption of cooked chickpea (2% and 10%) in ICR male mice in which colon cancer was induced with azoxymethane and dextran sulfate sodium. The effect of consumption of 2% or 10% cooked chickpeas on carcinogenesis-induced colon azoxymethane (AOM)/dextran sulfate sodium (DSS) in ICR mice was determined. Protein oxidation and lipids were determined by colorimetric methods and oxidation of DNA through the identification of adducts 8-hydroxy-2'-desoxiguanosine and proliferation markers (proliferating cell nuclear antigen [PCNA], Ki-67, and β-catenin), and inflammation (cyclooxygenase [COX]-2 and inducible nitric oxide synthase [iNOS]) were identified by immunohistochemistry reactions. The results showed the protective effect of daily consumption of rich cooked chickpeas in the carcinogenesis process, decreasing lipid, protein, and DNA oxidation and decreasing the expression of inflammatory enzymes (COX-2 and iNOS) as well as β-catenin, one of the most important oncogenic proteins in colon cancer. Animals that were fed with the 10% chickpea diet showed an inhibition in cellular proliferation (Ki-67 and PCNA expression). The addition of cooked chickpea seed (2% and 10%) to the daily diet is proposed as a chemopreventive agent against colon cancer.

  12. Extraction of antimony with tertiary amines.

    PubMed

    Alian, A; Sanad, W

    1967-06-01

    The extractability of antimony(III) and (V) with tridodecylamine from various aqueous solutions is reported. Extraction from nitric and hydrofluoric acid solutions is low, but extraction from sulphuric, hydrochloric and hydrobromic solutions is high. Antimony-(III) can be separated from antimony(V) in 7M nitric acid or 0.64M hydrobromic acid. The extraction of antimony from hydrochloric acid solutions in methanol, ethanol, and acetone-water mixtures is greater than from pure aqueous solutions of the same acidity. The elements from which antimony can be separated with tertiary amines are given.

  13. Mineral Resource of the Month: Antimony

    USGS Publications Warehouse

    Guberman, David E.

    2015-01-01

    Antimony is a lustrous silvery-white semimetal or metalloid. Archaeological and historical studies indicate that antimony and its mineral sulfides have been used by humans for at least six millennia. The alchemist Basil Valentine is sometimes credited with “discovering” the element; he described the extraction of metallic antimony from stibnite in his treatise “The Triumphal Chariot of Antimony,” published sometime between 1350 and 1600. In the early 18th century, Jöns Jakob Berzelius chose the periodic symbol for antimony (Sb) based on stibium, which is the Latin name for stibnite.

  14. First principles calculation of two dimensional antimony and antimony arsenide

    SciTech Connect

    Pillai, Sharad Babu Narayan, Som; Jha, Prafulla K.; Dabhi, Shweta D.

    2016-05-23

    This work focuses on the strain dependence of the electronic properties of two dimensional antimony (Sb) material and its alloy with As (SbAs) using density functional theory based first principles calculations. Both systems show indirect bandgap semiconducting character which can be transformed into a direct bandgap material with the application of relatively small strain.

  15. Luminal fructose inhibits rat intestinal sodium-phosphate cotransporter gene expression and phosphate uptake24

    PubMed Central

    Kirchner, Séverine; Muduli, Anjali; Casirola, Donatella; Prum, Kannitha; Douard, Véronique; Ferraris, Ronaldo P

    2008-01-01

    Background While searching by microarray for sugar-responsive genes, we inadvertently discovered that sodium-phosphate cotransporter 2B (NaPi-2b) mRNA concentrations were much lower in fructose-perfused than in glucose-perfused intestines of neonatal rats. Changes in NaPi-2b mRNA abundance by sugars were accompanied by similar changes in NaPi-2b protein abundance and in rates of inorganic phosphate (Pi) uptake. Objective We tested the hypothesis that luminal fructose regulates NaPi-2b. Design We perfused into the intestine fructose, glucose, and non-metabolizable or poorly transported glucose analogs as well as phlorizin. Results NaPi-2b mRNA concentrations and Pi uptake rates in fructose-perfused intestines were ≈30% of those in glucose and its analogs. NaPi-2b inhibition by fructose is specific because the mRNA abundance and activity of the fructose transporter GLUT5 (glucose transporter 5) increased with fructose perfusion, whereas those of other transporters were independent of the perfusate. Plasma Pi after 4 h of perfusion was independent of the perfusate, probably because normal kidneys can maintain normophosphatemia. Inhibiting glucose-6-phosphatase, another fructose-responsive gene, with tungstate or vanadate nonspecifically inhibited NaPi-2b mRNA expression and Pi uptake in both glucose- or fructose-perfused intestines. The AMP kinase (AMPK)–activator AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) enhanced and the fatty acid synthase–AMPK inhibitor C75 (3-carboxy-4-octyl-2-methylene-butyrolactone trans-4-carboxy-5-octyl-3-methylenebutyrolactone) prevented fructose inhibition of NaPi-2b but had no effect on expression of other transporters. NaPi-2b expression decreased markedly with age and was inhibited by fructose in all age groups. Conclusions Energy levels in enterocytes may play a role in NaPi-2b inhibition by luminal fructose. Consumption of fructose that supplies ≈10% of caloric intake by Americans clearly affects absorption of

  16. Sodium butyrate reverses the inhibition of Krebs cycle enzymes induced by amphetamine in the rat brain.

    PubMed

    Valvassori, Samira S; Calixto, Karen V; Budni, Josiane; Resende, Wilson R; Varela, Roger B; de Freitas, Karolina V; Gonçalves, Cinara L; Streck, Emilio L; Quevedo, João

    2013-12-01

    There is increasing interest in the possibility that mitochondrial impairment may play an important role in bipolar disorder (BD). The Krebs cycle is the central point of oxidative metabolism, providing carbon for biosynthesis and reducing agents for generation of ATP. Recently, studies have suggested that histone deacetylase (HDAC) inhibitors may have antimanic effects. The present study aims to investigate the effects of sodium butyrate (SB), a HDAC inhibitor, on Krebs cycle enzymes activity in the brain of rats subjected to an animal model of mania induced by D-amphetamine (D-AMPH). Wistar rats were first given D-AMPH or saline (Sal) for 14 days, and then, between days 8 and 14, rats were treated with SB or Sal. The citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH) were evaluated in the prefrontal cortex, hippocampus, and striatum of rats. The D-AMPH administration inhibited Krebs cycle enzymes activity in all analyzed brain structures and SB reversed D-AMPH-induced dysfunction analyzed in all brain regions. These findings suggest that Krebs cycle enzymes' inhibition can be an important link for the mitochondrial dysfunction seen in BD and SB exerts protective effects against the D-AMPH-induced Krebs cycle enzymes' dysfunction.

  17. Pharmacodynamic model of sodium-glucose transporter 2 (SGLT2) inhibition: implications for quantitative translational pharmacology.

    PubMed

    Maurer, Tristan S; Ghosh, Avijit; Haddish-Berhane, Nahor; Sawant-Basak, Aarti; Boustany-Kari, Carine M; She, Li; Leininger, Michael T; Zhu, Tong; Tugnait, Meera; Yang, Xin; Kimoto, Emi; Mascitti, Vincent; Robinson, Ralph P

    2011-12-01

    Sodium-glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through increased urinary glucose excretion (UGE). In this study, a biologically based pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was developed. The derived model was used to characterize the acute PK/PD relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative translational pharmacology of dapagliflozin was examined through both prospective simulation and direct modeling of mean literature data obtained for dapagliflozin in healthy subjects. Prospective simulations provided time courses of UGE that were of consistent shape to clinical observations, but were modestly biased toward under prediction. Direct modeling provided an improved characterization of the data and precise parameter estimates which were reasonably consistent with those predicted from preclinical data. Overall, these results indicate that the acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be reasonably well predicted from preclinical data through rational accounting of species differences in pharmacokinetics, physiology, and SGLT2 pharmacology. Because these data can be generated at the earliest stages of drug discovery, the proposed model is useful in the design and development of novel SGLT2 inhibitors. In addition, this model is expected to serve as a useful foundation for future efforts to understand and predict the effects of SGLT2 inhibition under chronic administration and in other patient populations.

  18. Sodium caffeate induces endothelial cell apoptosis and inhibits VEGF expression in cancer cells.

    PubMed

    Xu, Feng; Ou-Yang, Zhi-Gang; Zhang, Sheng-Hua; Song, Dan-Qing; Shao, Rong-Guang; Zhen, Yong-Su

    2006-06-01

    To investigate the induction of endothelial cell apoptosis and the suppression of VEGF expression in cancer cells by sodium caffeate (SCA). Apoptosis of transformed human umbilical vein endothelial cells (ECV304 cell line) was detected by flow cytometry, DNA electrophoresis assay and morphological assessment. Western blotting analysis was applied for determination of VEGF expression in cancer cells. Substrate degradation by type IV collagenase was measured by zymography. ELISA was used to detect the binding of type IV collagenase with relevant monoclonal antibody. SCA induced ECV304 cell apoptosis in a time- and dose-dependent manner. After treatment with 100 and 250 microg X mL(-1) of SCA for 48 h, DNA laddering appeared. SCA treated cells showed strong blue fluorescence and distinct changes of nuclear morphology, such as pyknosis and the occurrence of apoptotic bodies. VEGF expression in hepatoma HepG-2 cells and prostate carcinoma DU145 cells was reduced after SCA treatment. The degradation activity of type IV collagenase including MMP-2 and MMP-9 secreted by giant cell pulmonary carcinoma PG cells was inhibited by SCA in a dose-dependent manner. SCA also reduced the binding of mAb 3D6, a relevant monoclonal antibody, to type IV collagenase. SCA can induce endothelial cell apoptosis and inhibit VEGF expression as well as type IV collagenase activity in cancer cells. SCA might be active in modulating tumor angiogenesis and the microenvironment.

  19. Elucidation of the mechanism of enzymatic browning inhibition by sodium chlorite.

    PubMed

    He, Qiang; Luo, Yaguang; Chen, Pei

    2008-10-15

    Sodium chlorite (SC) is a well known anti-microbial agent and its strong inhibitory effect on enzymatic browning of fresh-cut produce has recently been identified. We investigated the effect of SC on polyphenol oxidase (PPO) and its substrate, chlorogenic acid (CA), as it relates to the mechanisms of browning inhibition by SC. Results indicate that the browning reaction of CA (1.0mM) catalyzed by PPO (33U/mL) was significantly inhibited by 1.0mM SC at pH 4.6. Two PPO isoforms were identified by native polyacrylamide gel electrophoresis, and both were inactivated by SC (3.0mM). This suggests that SC serves as a PPO inhibitor to prevent enzymatic browning. Furthermore, the effect of SC on the stability of CA in both acidic (pH 4.5) and basic conditions (pH 8.3) was studied by UV-Vis scan and LC-MS analysis. The results showed that at the presence of SC (3.0mM), CA (0.1mM) degraded to quinic acid and caffeic acid as well as other intermediates. Hence, the anti-browning property of SC can be attributed to the two modes of action: the inactivation of polyphenol oxidase directly and the oxidative degradation of phenolic substrates. Published by Elsevier Ltd.

  20. Sodium glucose transporter-2 inhibition has no renoprotective effects on non-diabetic chronic kidney disease.

    PubMed

    Ma, Qiuyue; Steiger, Stefanie; Anders, Hans-Joachim

    2017-04-01

    Sodium glucose transporter (SGLT)-2 inhibition has renoprotective effects in diabetic kidney disease. Whether similar effects can be achieved also in non-diabetic kidney disease is speculative. Chronic kidney disease was induced in C57BL/6N mice by feeding an oxalate-rich diet for 14 days, known to induce nephrocalcinosis-related tubular atrophy and interstitial fibrosis without directly affecting the glomerular compartment. Empagliflozin treatment started from day 0 of oxalate feeding had no effect on the decline of glomerular filtration rate, crystal deposition, blood urea nitrogen or serum creatinine levels on day 7 and 14. Tissue morphometry of tubular injury and kidney mRNA levels of kidney injury molecule-1 or tissue inhibitor of metalloproteinase-2 were comparable between empagliflozin- and vehicle-treated mice with oxalate nephropathy on day 7 and 14. Similarly, empagliflozin did not affect markers of interstitial fibrosis, including silver, alpha smooth muscle actin (αSMA) and collagen 1 staining, and mRNA levels of fibronectin-1, collagen 1α1, fibroblast-specific protein-1, and transforming growth factor (TGF)-β2 on day 7 and 14. Thus, the specific renoprotective mechanisms-of-action of SGLT2 inhibition in diabetic kidney disease do not apply to chronic oxalosis, a non-diabetic form of chronic kidney disease.

  1. Project Overview: Inhibition of the Sodium-Iodide Symporter by Perchlorate: Evaluation of Lifestage Sensitivity Using PBPK Modeling

    EPA Science Inventory

    Perchlorate (ClO4-) competitively inhibits uptake of iodide by the sodium-iodide symporter (NIS) in laboratory animals and humans. NIS is found in many tissues, but is primarily responsible for sequestering iodide into the thyroid, enabling biosynthesis of thyroid hormones. The N...

  2. Project Overview: Inhibition of the Sodium-Iodide Symporter by Perchlorate: Evaluation of Lifestage Sensitivity Using PBPK Modeling

    EPA Science Inventory

    Perchlorate (ClO4-) competitively inhibits uptake of iodide by the sodium-iodide symporter (NIS) in laboratory animals and humans. NIS is found in many tissues, but is primarily responsible for sequestering iodide into the thyroid, enabling biosynthesis of thyroid hormones. The N...

  3. Inhibition of several enzymes by gold compounds. II. beta-Glucuronidase, acid phosphatase and L-malate dehydrogenase by sodium thiomalatoraurate (I), sodium thiosulfatoaurate (I) and thioglucosoaurate (I).

    PubMed

    Lee, M T; Ahmed, T; Haddad, R; Friedman, M E

    1989-01-01

    Bovine liver beta-D-glucuronide glucuronohydrolase, EC 3.2.1.32), wheat germ acid phosphatase (orthophosphoric monoesterphosphohydrolase, EC 3.1.3.2) and bovine liver L-malate dehydrogenase (L-malate: NAD oxidoreductase, EC 1.1.1.37) were inhibited by a series of gold (I) complexes that have been used as anti-inflammatory drugs. Both sodium thiosulfatoaurate (I) (Na AuTs) and sodium thiomalatoraurate (NaAuTM) effectively inhibited all three enzymes, while thioglucosoaurate (I) (AuTG) only inhibited L-malate dehydrogenase. The equilibrium constants (K1) ranged from nearly 4000 microM for the NaAuTM-beta-glucuronidase interaction to 24 microM for the NaAuTS-beta-glucuronidase interaction. The rate of covalent bond formation (kp) ranged from 0.00032 min-1 for NaAuTM-beta-glucuronidase formation to 1.7 min-1 for AuTG-L-malate dehydrogenase formation. The equilibrium data shows that the gold (I) drugs bind by several orders lower than the gold (III) compounds, suggesting a significantly stronger interaction between the more highly charged gold ion and the enzyme. Yet the rate of covalent bond formation depends as much on the structure of the active site as upon the lability of the gold-ligand bond. It was also observed that the more effective the gold inhibition the more toxic the compound.

  4. Partial Inhibition of Sodium/Calcium Exchange Restores Cellular Calcium Handling in Canine Heart Failure

    PubMed Central

    Hobai, Ion A.; Maack, Christoph; O'Rourke, Brian

    2009-01-01

    Sodium/calcium (Na+/Ca2+) exchange (NCX) overexpression is common to human heart failure and heart failure in many animal models, but its specific contribution to the cellular Ca2+ ([Ca2+]i) handling deficit is unclear. Here, we investigate the effects of exchange inhibitory peptide (XIP) on Ca2+ handling in myocytes isolated from canine tachycardic pacing-induced failing hearts. Whole-cell patch-clamped left ventricular myocytes from failing hearts (F) showed a 52% decrease in steady-state sarcoplasmic reticulum (SR) Ca2+ load and a 44% reduction in the amplitude of the [Ca2+]i transient, as compared with myocytes from normal hearts (N). Intracellular application of XIP (30 μmol/L) normalized the [Ca2+]i transient amplitude in F (3.86-fold increase), concomitant with a similar increase in SR Ca2+ load. The degree of NCX inhibition at this concentration of XIP was ≈27% and was selective for NCX: L-type Ca2+ currents and plasmalemmal Ca2+ pumps were not affected. XIP also indirectly improved the rate of [Ca2+]i removal at steady-state, secondary to Ca2+-dependent activation of SR Ca2+ uptake. The findings indicate that in the failing heart cell, NCX inhibition can improve SR Ca2+ load by shifting the balance of Ca2+ fluxes away from trans-sarcolemmal efflux toward SR accumulation. Hence, inhibition of the Ca2+ efflux mode of the exchanger could potentially be an effective therapeutic strategy for improving contractility in congestive heart failure. PMID:15217911

  5. Sigma receptor activation inhibits voltage-gated sodium channels in rat intracardiac ganglion neurons

    PubMed Central

    Zhang, Hongling; Katnik, Christopher; Cuevas, Javier

    2010-01-01

    Sigma (σ) receptors have been shown to regulate multiple ion channel types in intracardiac ganglion neurons, including voltage-gated calcium and potassium channels. However, the inhibition of these channels alone cannot fully account for σ receptor-induced changes in neuronal excitability previously reported. Whole-cell patch clamp experiments were conducted under current-clamp mode in isolated intracardiac neurons from neonatal rats to assess the effects of σ receptor activation on the active membrane properties of these cells. Bath application of the pan-selective σ receptor agonist, 1,3-Di-o-tolylguanidine (DTG), and the σ-1-selective agonist, (+)-pentazocine, significantly increased the action potential latency and decreased action potential overshoot in response to depolarizing current ramps, which suggests inhibition of voltage-gated sodium channels. Whole-cell voltage clamp experiments showed that these σ agonists reversibly decrease depolarization-activated Na+ currents in these cells at all potentials tested. The peak currents generated by membrane depolarizations were decreased in a dose dependent manner with IC50 values for DTG and (+)-pentazocine of 32 μM and 49 μM, respectively. The σ-1 receptor-selective antagonist, BD 1063 (100 nM), inhibited DTG (30 μM) block of Na+ currents by ∼ 50%, suggesting that the effects are mediated by activation of σ-1 receptors. DTG also shifted the steady-state inactivation curve of Na+ channels to more negative potentials, with the membrane potential of half-activation shifting from -49 mV to -63 mV in the absence and presence of 30 μM DTG, respectively. Taken together, these results suggest that σ-1 receptor activation decreases intracardiac ganglion neuron excitability by modulating voltage-gated Na+ channels. PMID:21383893

  6. Human serum paraoxonase-1 (hPON1): in vitro inhibition effects of moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium.

    PubMed

    Türkeş, Cüneyt; Söyüt, Hakan; Beydemir, Şükrü

    2015-01-01

    In this study, we investigated the effects of antibacterial drugs (moxifloxacin hydrochloride, levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium) on human serum paraoxonase-1 (hPON1) enzyme activity from human serum in vitro conditions. For this purpose, hPON1 enzyme was purified from human serum using simple chromatographic methods. The antibacterial drugs exhibited inhibitory effects on hPON1 at low concentrations. Ki constants were calculated to be 2.641 ± 0.040 mM, 5.525 ± 0.817 mM, 35.092 ± 1.093 mM, 252.762 ± 5.749 mM and 499.244 ± 10.149 mM, respectively. The inhibition mechanism of moxifloxacin hydrochloride was competitive, whereas levofloxacin hemihidrate, cefepime hydrochloride, cefotaxime sodium and ceftizoxime sodium were noncompetitive inhibitors.

  7. Isoflurane Inhibits the Tetrodotoxin-resistant Voltagegated Sodium Channel Nav1.8

    PubMed Central

    Herold, Karl F.; Nau, Carla; Ouyang, Wei; Hemmings, Hugh C.

    2009-01-01

    Background Voltage-gated sodium channels (Nav) mediate neuronal action potentials. Tetrodotoxin inhibits all Nav isoforms, but Nav1.8 and Nav1.9 are relatively tetrodotoxin-resistant (TTX-r) compared to other isoforms. Nav1.8 is highly expressed in dorsal root ganglion neurons and is functionally linked to nociception, but the sensitivity of TTX-r isoforms to inhaled anesthetics is unclear. Methods The sensitivities of heterologously expressed rat TTX-r Nav1.8 and endogenous tetrodotoxin-sensitive (TTX-s) Nav to the prototypic inhaled anesthetic isoflurane were tested in mammalian ND7/23 cells using patch-clamp electrophysiology. Results From a holding potential of −70 mV, isoflurane (0.53±0.06 mM, ~1.8 MAC at 24°C) reduced normalized peak Na+ current (INa) of Nav1.8 to 0.55±0.03 and of endogenous TTX-s Nav to 0.56±0.06. Isoflurane minimally inhibited INa from a holding potential of −140 mV. Isoflurane did not affect voltage-dependence of activation, but significantly shifted voltage-dependence of steady-state inactivation by −6 mV for Nav1.8 and by −7 mV for TTX-s Nav. IC50 values for inhibition of peak INa were 0.67±0.06 mM for Nav1.8 and 0.66±0.09 mM for TTX-s Nav; significant inhibition occurred at clinically relevant concentrations as low as 0.58 MAC. Isoflurane produced use-dependent block of Nav1.8; at a stimulation frequency of 10 Hz, 0.56±0.08 mM isoflurane reduced INa to 0.64±0.01 vs. 0.78±0.01 for control. Conclusion Isoflurane inhibited the tetrodotoxin-resistant isoform Nav1.8 with potency comparable to that for endogenous tetrodotoxin-sensitive Nav isoforms, indicating that sensitivity to inhaled anesthetics is conserved across diverse Nav family members. Block of Nav1.8 in dorsal root ganglion neurons could contribute to the effects of inhaled anesthetics on peripheral nociceptive mechanisms. PMID:19672182

  8. Inhibition of frog skeletal muscle sodium channels by newly synthesized chiral derivatives of mexiletine and tocainide.

    PubMed

    De Luca, A; Natuzzi, F; Falcone, G; Duranti, A; Lentini, G; Franchini, C; Tortorella, V; Camerino, D C

    1997-12-01

    To search for potent use-dependent blockers of skeletal muscle sodium channels as potential antimyotonic agents, the actions of newly synthesized chiral analogs of mexiletine and tocainide were tested in vitro on sodium currents of single fibers of frog semitendinosus muscle by vaseline-gap voltage clamp method. The effect of each drug on the maximal peak Na+ transient (I(Na) max) was evaluated as both tonic and use-dependent block by using infrequent depolarizing stimulation and trains of pulses at 2-10 Hz frequency, respectively. The mexiletine analog 3-(2,6-dimethylphenoxy)-2-methylpropanamine (Me2), having an increased distance between the phenyl and the amino groups, was less potent than mexiletine in producing a tonic block but produced a remarkable use-dependent block. In fact, the half-maximal concentration (IC50) for tonic block of S(-)-Me2 was 108 microM vs. 54.5 microM of R(-)-mexiletine, but the IC50 was 6.2 times lowered by the 10 Hz stimulation with respect to the 2.4 fold decrease observed with mexiletine. The R(-)-mexiletine and the S(-)-Me2 were about twofold more potent than the corresponding enantiomers in producing a tonic block, but the stereoselectivity attenuated during use-dependent blockade. The more lipophilic 2-(4-chloro-2-methylphenoxy)-1-phenylethylamine (Me1), presently available as raceme, produced a potent and irreversible tonic block of the sodium currents with an IC50 of 29 microM, but had a less pronounced use-dependent inhibition, with a 1.9 fold decrease of the IC50 at 10 Hz. The R(-) isomer of 2',6'-valinoxylidide (To1), a tocainide derivative with an increased hindrance on the chiral carbon atom, was twofold (IC50 = 209 microM) and tenfold (IC50 = 27.4 microM) more potent than R(-)-tocainide in tonic and use-dependent block, respectively. Tocainide was almost devoid of stereoselectivity, whereas the eudismic ratio of To1 [(IC50 S(+)-To1/IC50 R(-)-To1] was 1.7. As for mexiletine and Me2, the stereoselectivity of To1 was the

  9. Synergy between chronic corticosterone and sodium azide treatments in producing a spatial learning deficit and inhibiting cytochrome oxidase activity.

    PubMed Central

    Bennett, M C; Mlady, G W; Fleshner, M; Rose, G M

    1996-01-01

    Previously, we developed a rat model of persistent mitochondrial dysfunction based upon the chronic partial inhibition of the mitochondrial enzyme cytochrome oxidase (EC 1.9.3.1). Continuous systemic infusion of sodium azide at approximately 1 mg/kg per hr inhibited cytochrome oxidase activity and produced a spatial learning deficit. In other laboratories, glucocorticoids have been reported to exacerbate neuronal damage from various acute metabolic insults. Therefore, we tested the hypothesis that corticosterone, the primary glucocorticoid in the rat, would potentiate the sodium azide-induced learning deficit. To this end, we first identified nonimpairing doses of sodium azide (approximately 0.75 mg/kg per hr) and corticosterone (100-mg pellet, 3-week sustained-release). We now report that chronic co-administration of these individually nonimpairing treatments produced a severe learning deficit. Moreover, the low dose of corticosterone, which did not elevate serum corticosterone, acted synergistically with sodium azide to inhibit cytochrome oxidase activity. The latter result represents a previously unidentified effect of glucocorticoids that provides a candidate mechanism for glucocorticoid potentiation of neurotoxicity induced by metabolic insult. These results may have the clinical implication of expanding the definition of hypercortisolism in patient populations with compromised oxidative metabolism. Furthermore, they suggest that glucocorticoid treatment may contribute to pathology in disease or trauma conditions that involve metabolic insult. PMID:8577764

  10. 40 CFR 421.140 - Applicability: Description of the primary antimony subcategory.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... primary antimony subcategory. 421.140 Section 421.140 Protection of Environment ENVIRONMENTAL PROTECTION... CATEGORY Primary Antimony Subcategory § 421.140 Applicability: Description of the primary antimony... antimony at primary antimony facilities. ...

  11. 40 CFR 421.140 - Applicability: Description of the primary antimony subcategory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... primary antimony subcategory. 421.140 Section 421.140 Protection of Environment ENVIRONMENTAL PROTECTION... CATEGORY Primary Antimony Subcategory § 421.140 Applicability: Description of the primary antimony... antimony at primary antimony facilities. ...

  12. 40 CFR 421.140 - Applicability: Description of the primary antimony subcategory.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... primary antimony subcategory. 421.140 Section 421.140 Protection of Environment ENVIRONMENTAL PROTECTION... CATEGORY Primary Antimony Subcategory § 421.140 Applicability: Description of the primary antimony... antimony at primary antimony facilities. ...

  13. 40 CFR 421.140 - Applicability: Description of the primary antimony subcategory.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... primary antimony subcategory. 421.140 Section 421.140 Protection of Environment ENVIRONMENTAL PROTECTION... CATEGORY Primary Antimony Subcategory § 421.140 Applicability: Description of the primary antimony... antimony at primary antimony facilities. ...

  14. 40 CFR 421.140 - Applicability: Description of the primary antimony subcategory.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... primary antimony subcategory. 421.140 Section 421.140 Protection of Environment ENVIRONMENTAL PROTECTION... CATEGORY Primary Antimony Subcategory § 421.140 Applicability: Description of the primary antimony... antimony at primary antimony facilities. ...

  15. Inhibition of tumour necrosis factor-alpha (TNF-alpha) release from mast cells by the anti-inflammatory drugs, sodium cromoglycate and nedocromil sodium.

    PubMed

    Bissonnette, E Y; Enciso, J A; Befus, A D

    1995-10-01

    TNF-alpha is a cytokine thought to be involved in the pathogenesis of asthma and in several other inflammatory conditions. Given recent evidence that mast cells (MC) are an important source of TNF-alpha, we investigated the effects of two anti-inflammatory drugs, nedocromil sodium (NED) and sodium cromoglycate (SCG), on rat MC-derived TNF-alpha. We established that at least 2 h pretreatment with NED or SCG followed by washing was required to inhibit TNF-alpha-dependent cytotoxicity by rat peritoneal MC (PMC). A maximum inhibition of TNF-alpha occurred after 6 h treatment. The inhibitory effect of NED and SCG (10(-5)-10(-3)M) was concentration-dependent (20-37% for NED and 16-37% for SCG). The time-course analysis and the use of cycloheximide, an inhibitor of protein synthesis, provided strong evidence that new protein synthesis by the MC is required for this inhibitory effect. Furthermore, 24 h treatment with 1 mM NED inhibited the levels of mRNA for TNF-alpha by 59-83%. In addition to the effect on TNF-alpha-dependent cytotoxicity by MC, 20 min pretreatment with 10(-4) M NED and SCG inhibited antigen-stimulated TNF-alpha release (6h) by 42% and 48%, respectively. Interestingly, the functionally distinct intestinal mucosal MC (IMMC) is unresponsive to these drugs with regard to histamine secretion. However, as with PMC, 2h pretreatment with NED or SCG inhibited TNF-alpha-dependent cytotoxicity by IMMC. These effects may be important in the action of these drugs in vivo in the late phase reaction in asthma or other inflammatory conditions.

  16. Inhibition of tumour necrosis factor-alpha (TNF-alpha) release from mast cells by the anti-inflammatory drugs, sodium cromoglycate and nedocromil sodium.

    PubMed Central

    Bissonnette, E Y; Enciso, J A; Befus, A D

    1995-01-01

    TNF-alpha is a cytokine thought to be involved in the pathogenesis of asthma and in several other inflammatory conditions. Given recent evidence that mast cells (MC) are an important source of TNF-alpha, we investigated the effects of two anti-inflammatory drugs, nedocromil sodium (NED) and sodium cromoglycate (SCG), on rat MC-derived TNF-alpha. We established that at least 2 h pretreatment with NED or SCG followed by washing was required to inhibit TNF-alpha-dependent cytotoxicity by rat peritoneal MC (PMC). A maximum inhibition of TNF-alpha occurred after 6 h treatment. The inhibitory effect of NED and SCG (10(-5)-10(-3)M) was concentration-dependent (20-37% for NED and 16-37% for SCG). The time-course analysis and the use of cycloheximide, an inhibitor of protein synthesis, provided strong evidence that new protein synthesis by the MC is required for this inhibitory effect. Furthermore, 24 h treatment with 1 mM NED inhibited the levels of mRNA for TNF-alpha by 59-83%. In addition to the effect on TNF-alpha-dependent cytotoxicity by MC, 20 min pretreatment with 10(-4) M NED and SCG inhibited antigen-stimulated TNF-alpha release (6h) by 42% and 48%, respectively. Interestingly, the functionally distinct intestinal mucosal MC (IMMC) is unresponsive to these drugs with regard to histamine secretion. However, as with PMC, 2h pretreatment with NED or SCG inhibited TNF-alpha-dependent cytotoxicity by IMMC. These effects may be important in the action of these drugs in vivo in the late phase reaction in asthma or other inflammatory conditions. Images Fig. 6 PMID:7554404

  17. SKF-96365 strongly inhibits voltage-gated sodium current in rat ventricular myocytes.

    PubMed

    Chen, Kui-Hao; Liu, Hui; Yang, Lei; Jin, Man-Wen; Li, Gui-Rong

    2015-06-01

    SKF-96365 (1-(beta-[3-(4-methoxy-phenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride) is a general TRPC channel antagonist commonly used to characterize the potential functions of TRPC channels in cardiovascular system. Recent reports showed that SKF-96365 induced a reduction in cardiac conduction. The present study investigates whether the reduced cardiac conduction caused by SKF-96365 is related to the blockade of voltage-gated sodium current (I Na) in rat ventricular myocytes using the whole-cell patch voltage-clamp technique. It was found that SKF-96365 inhibited I Na in rat ventricular myocytes in a concentration-dependent manner. The compound (1 μM) negatively shifted the potential of I Na availability by 9.5 mV, increased the closed-state inactivation of I Na, and slowed the recovery of I Na from inactivation. The inhibition of cardiac I Na by SKF-96365 was use-dependent and frequency-dependent, and the IC₅₀ was decreased from 1.36 μM at 0.5 Hz to 1.03, 0.81, 0.61, 0.56 μM at 1, 2, 5, 10 Hz, respectively. However, the selective TRPC3 antagonist Pyr3 decreased cardiac I Na by 8.5% at 10 μM with a weak use and frequency dependence. These results demonstrate that the TRPC channel antagonist SKF-96365 strongly blocks cardiac I Na in use-dependent and frequency-dependent manners. Caution should be taken for interpreting the alteration of cardiac electrical activity when SKF-96365 is used in native cells as a TRPC antagonist.

  18. Glutathione-Induced Conversion of Pentavalent Antimony to Trivalent Antimony in Meglumine Antimoniate

    PubMed Central

    Frézard, Frédéric; Demicheli, Cynthia; Ferreira, Claúdio S.; Costa, Michelle A. P.

    2001-01-01

    The standard treatment of human leishmaniases involves the use of pentavalent antimony [Sb(V)] compounds, including meglumine antimoniate. The mode of action of these compounds has not been fully elucidated. The possibility that Sb(III) is involved has been suggested; however, the biomolecule that may induce the conversion of Sb(V) to Sb(III) has not yet been identified. In the present study, we investigated both the ability of reduced glutathione (GSH) to promote the reduction of Sb(V) into Sb(III) in meglumine antimoniate and the effects of pH and temperature on this transformation. GSH did promote the reduction of Sb(V) into Sb(III) in a dose-dependent manner. When GSH and meglumine antimoniate were incubated together at a GSH/Sb molar ratio superior or equal to 5:1, all antimony was encountered in the reduced form, indicating a stoichiometry of 5:1 between GSH and Sb(V) in the reaction. The reaction between Sb(V) and GSH was favored at an acidic pH (pH 5) and an elevated temperature (37°C), conditions found within the phagolysosome, in which Leishmania resides. For instance, about 30% of the Sb(V) (concentration, 2mM) was converted to Sb(III) following incubation for 3 days with 10 mM GSH at pH 5 and 37°C. Our data support the hypothesis that Sb(V) would be converted by GSH, or a related thiol compound, to more toxic Sb(III) in the phagolysosome of macrophages. PMID:11181379

  19. Poly(vinyl alcohol)/sodium alginate/layered silicate based nanofibrous mats for bacterial inhibition.

    PubMed

    Li, Wei; Li, Xueyong; Chen, Yang; Li, Xiaoxia; Deng, Hongbing; Wang, Ting; Huang, Rong; Fan, Gang

    2013-02-15

    Poly(vinyl alcohol) (PVA)/sodium alginate (ALG)/organic rectorite (OREC) composite nanofibrous mats are fabricated by electrospinning aqueous solutions with different mixing ratios. Both good fiber shape and three-dimensional structure of nanofibrous mats can be observed by Field Emission Scanning Electron Microscopy. Energy-dispersive X-ray spectroscopy shows the existence of OREC in the as-spun composite mats. In addition, small-angle X-ray diffraction confirms that the interlayer of OREC is intercalated by ALG/PVA chains, and the distance between OREC interlayers is increased from 4.50 to 4.74 nm. Wide angle X-ray diffraction and Fourier transform infrared spectra further verify the intercalation is between polymers and layered silicate. Moreover, the thermal gravimetric analysis shows that the addition of OREC has only a small effect on the thermal stability of composites. Furthermore, the antibacterial experiments illustrate that OREC can enhance the bacterial inhibition ability of nanofibrous mats against Escherichia coli and Staphylococcus aureus.

  20. Sodium alginate ameliorates indomethacin-induced gastrointestinal mucosal injury via inhibiting translocation in rats

    PubMed Central

    Yamamoto, Atsuki; Itoh, Tomokazu; Nasu, Reishi; Nishida, Ryuichi

    2014-01-01

    AIM: To investigate the effects of sodium alginate (AL-Na) on indomethacin-induced small intestinal lesions in rats. METHODS: Gastric injury was assessed by measuring ulcerated legions 4 h after indomethacin (25 mg/kg) administration. Small intestinal injury was assessed by measuring ulcerated legions 24 h after indomethacin (10 mg/kg) administration. AL-Na and rebamipide were orally administered. Myeloperoxidase activity in the stomach and intestine were measured. Microvascular permeability, superoxide dismutase content, glutathione peroxidase activity, catalase activity, red blood cell count, white blood cell count, mucin content and enterobacterial count in the small intestine were measured. RESULTS: AL-Na significantly reduced indomethacin-induced ulcer size and myeloperoxidase activity in the stomach and small intestine. AL-Na prevented increases in microvascular permeability, superoxide dismutase content, glutathione peroxidase activity and catalase activity in small intestinal injury induced by indomethacin. AL-Na also prevented decreases in red blood cells and white blood cells in small intestinal injury induced by indomethacin. Moreover, AL-Na suppressed mucin depletion by indomethacin and inhibited infiltration of enterobacteria into the small intestine. CONCLUSION: These results indicate that AL-Na ameliorates non-steroidal anti-inflammatory drug-induced small intestinal enteritis via bacterial translocation. PMID:24627600

  1. Volatile anesthetics inhibit sodium channels without altering bulk lipid bilayer properties

    PubMed Central

    Sanford, R. Lea; Lee, William; Schultz, Margaret F.; Ingólfsson, Helgi I.

    2014-01-01

    Although general anesthetics are clinically important and widely used, their molecular mechanisms of action remain poorly understood. Volatile anesthetics such as isoflurane (ISO) are thought to alter neuronal function by depressing excitatory and facilitating inhibitory neurotransmission through direct interactions with specific protein targets, including voltage-gated sodium channels (Nav). Many anesthetics alter lipid bilayer properties, suggesting that ion channel function might also be altered indirectly through effects on the lipid bilayer. We compared the effects of ISO and of a series of fluorobenzene (FB) model volatile anesthetics on Nav function and lipid bilayer properties. We examined the effects of these agents on Nav in neuronal cells using whole-cell electrophysiology, and on lipid bilayer properties using a gramicidin-based fluorescence assay, which is a functional assay for detecting changes in lipid bilayer properties sensed by a bilayer-spanning ion channel. At clinically relevant concentrations (defined by the minimum alveolar concentration), both the FBs and ISO produced prepulse-dependent inhibition of Nav and shifted the voltage dependence of inactivation toward more hyperpolarized potentials without affecting lipid bilayer properties, as sensed by gramicidin channels. Only at supra-anesthetic (toxic) concentrations did ISO alter lipid bilayer properties. These results suggest that clinically relevant concentrations of volatile anesthetics alter Nav function through direct interactions with the channel protein with little, if any, contribution from changes in bulk lipid bilayer properties. Our findings further suggest that changes in lipid bilayer properties are not involved in clinical anesthesia. PMID:25385786

  2. Geomicrobial interactions with arsenic and antimony

    USGS Publications Warehouse

    Oremland, Ronald S.

    2015-01-01

    Although arsenic and antimony are generally toxic to life, some microorganisms exist that can metabolize certain forms of these elements. Some can use arsenite or stibnite as potential or sole energy sources, whereas others can use aresenate and antimonite (as was discovered only recently) as terminal electron acceptors. Still other microbes can metabolize arsenic and antimony compounds to detoxify them. These reactions are important from a geomicrobial standpoint because they indicate that a number of microbes contribute to arsenic and antimony mobilization or immobilization in the environment and play a role in arsenic and antimony cycles. Recent reviews include five on prokaryotes and arsenic metabolism, a review with an arsenic perspective on biomining, and a series on environmental antimony, including one about antimony and its interaction with microbiota.

  3. β-Escin sodium inhibits inducible nitric oxide synthase expression via downregulation of the JAK/STAT pathway in A549 cells.

    PubMed

    Ji, Deng Bo; Xu, Bo; Liu, Jing Tao; Ran, Fu Xiang; Cui, Jing Rong

    2011-12-01

    β-escin, a triterpene saponin, is one of the major active compounds extracted from horse chestnut (Aesculus hippocastanum) seed. Previous work has found that β-escin sodium has antiinflammatory and antitumor effects. In the present study, we investigated its effect on cell proliferation and inducible nitric-oxide synthase (iNOS) expression in human lung carcinoma A549 cells. β-escin sodium (5-40 µg/mL) inhibited cytokine mixture (CM)-induced nitric oxide (NO) production in A549 cells by reducing the expression of iNOS. β-escin sodium suppressed phosphorylation and nuclear translocation of STAT1 (Tyr701) and STAT3 (Tyr705) induced by CM but did not affect the activation of c-Jun and NF-κB. β-escin sodium inhibited the activation of protein tyrosine kinase JAK2. Pervanadate treatment reversed the β-escin sodium-induced downregulation of STAT3 and STAT1. β-escin sodium treatment enhanced an activating phosphorylation of the phosphatase SHP2. Small interfering RNA-mediated knockdown of SHP2 inhibited β-escin sodium-induced phospho-STAT dephosphorylation. Moreover β-escin sodium reduced the activation of p38 MAPK. Finally, β-escin sodium inhibited the proliferation of A549 cells, did not change the cell membrane's permeability, nuclear morphology and size and the mitochondria's transmembrane potential of A549 cells. Taken together, these results demonstrate that β-escin sodium could downregulate iNOS expression through inhibiting JAK/STAT signaling and p38 MAPK activation in A549 cells. β-escin sodium has a marked antiproliferative effect on A549 cells at least in part by inhibiting the JAK/STAT signaling pathway, but not by a cytotoxic effect. β-escin sodium would be useful as a chemopreventive agent or a therapeutic against inflammatory-associated tumor. © 2011 Wiley Periodicals, Inc. Copyright © 2011 Wiley Periodicals, Inc.

  4. The mechanism by which cytoplasmic protons inhibit the sodium-calcium exchanger in guinea-pig heart cells.

    PubMed Central

    Doering, A E; Lederer, W J

    1993-01-01

    1. We recorded cardiac sodium-calcium exchange current (INa-Ca) in giant excised membrane patches obtained from cardiac myocytes of the adult guinea-pig. 2. Rapid changes in ion concentrations on the cytoplasmic side of the excised membrane patch were produced using a modified oil-gate bath. 3. Sodium-calcium exchange current was activated by step increases in sodium concentration on the cytoplasmic side of the membrane ([Na+]i), which led to an increase in outward INa-Ca to a new steady-state level. The [Na+]i required to half-maximally activate the sodium-calcium exchange current (K1/2) was 21 mM. 4. Step increases in cytoplasmic calcium concentration ([Ca2+]i) stimulated the [Na+]i-activated INa-Ca up to 1 microM [Ca2+]i, then inhibited the exchange current at very high [Ca2+]i (1 mM). 5. A step decrease in cytoplasmic pH from 7.2 to 6.4 (increase in [H+]i) produced a biphasic but monotonic decrease in INa-Ca. Alkalinization of cytoplasmic pH from 7.2 to 8.0 caused a large, biphasic increase in INa-Ca. 6. When INa-Ca was activated by a step increase in [Na+]i and [H+]i was simultaneously increased, the outward current rose to a peak and then declined to a low steady level. The peak current seen was always less than the maximum current produced by an identical elevation of [Na+]i at constant pHi. This reduction in peak outward current reflected a rapid 'primary' inhibition of the sodium-calcium exchange by protons. The decay of the sodium-calcium exchange current following the peak was slow and corresponded to the time course of the onset of a 'secondary' proton block. 7. Rapid primary inhibition of the sodium-calcium exchanger could also be produced by cytoplasmic acidification in the absence of cytoplasmic sodium. The primary blockade was revealed when a subsequent increase in [Na+]i activated INa-Ca and a smaller peak outward current was observed. Secondary inhibition of the sodium-calcium exchanger was not, however, produced by cytoplasmic acidification in

  5. Experimental and clinical studies with a new antimonial preparation for the treatment of schistosomiasis

    PubMed Central

    Pedrique, Miguel Ron; Ercoli, Nicolò

    1971-01-01

    This paper presents the results of a clinical study in which a new antimony preparation—a chelate of dimethylcysteine with antimony sodium tartrate (”NAP”)—was administered intramuscularly at a total dosage of 2 g (5×400 mg, corresponding to 290 mg of Sb) to 400 patients with schistosomiasis. Among 108 patients in a rural population the treatment was on the whole well accepted (97% completed the intensive course of injections), thus indicating that NAP would be useful for the mass treatment of schistosomiasis. PMID:5317079

  6. Inhibition of small-intestinal sugar absorption mediated by sodium orthovanadate Na3VO4 in rats and its mechanisms

    PubMed Central

    Ai, Jing; Du, Jie; Wang, Ning; Du, Zhi-Min; Yang, Bao-Feng

    2004-01-01

    AIM: To investigate the inhibitory effects of sodium orthovanadate on small-intestinal glucose and maltose absorption in rats and its mechanism. METHODS: Normal Wistar rats were lavaged with sodium orthovanadate (16 mg/kg, 4 mg/kg and 1 mg/kg) for 6 d. Blood glucose values were measured after fasting and 0.5, 1, 1.5 and 2 h after glucose and maltose feeding with oxidation-enzyme method. α-glucosidase was abstracted from the upper small intestine, and its activity was examined. mRNA expression of α-glucosidase and glucose-transporter 2 (GLUT2) in epithelial cells of the small intestine was observed by in situ hybridization. RESULTS: Sodium orthovanadate could delay the increase of plasma glucose concentration after glucose and maltose loading, area under curve (AUC) in these groups was lower than that in control group. Sodium orthovanadate at dosages of 10 μmol/L, 100 μmol/L and 1000 μmol/L could suppress the activity of α-glucosidase in the small intestine of normal rats, with an inhibition rate of 68.18%, 87.22% and 91.91%, respectively. Sodium orthovanadate reduced mRNA expression of α-glucosidase and GLUT2 in epithelial cells of small intestine. CONCLUSION: Sodium orthovanadate can reduce and delay the absorption of glucose and maltose. The mechanism may be that it can inhibit the activity and mRNA expression of α-glucosidase, as well as mRNA expression of GLUT2 in small intestine. PMID:15534916

  7. FIRST REPORT ON OTOTOXICITY OF MEGLUMINE ANTIMONIATE

    PubMed Central

    Valete-Rosalino, Cláudia Maria; Araujo-Melo, Maria Helena; Bezerra, Débora Cristina de Oliveira; de Barcelos, Renata Oliveira; de Melo-Ferreira, Vanessa; Torraca, Tânia Salgado de Sousa; Martins, Ana Cristina da Costa; Moreira, João Soares; Vargas, Mirian Catherine Melgares; Braga, Frederico Pereira Bom; Salgueiro, Mariza de Matos; Saheki, Maurício Naoto; Schubach, Armando Oliveira

    2014-01-01

    Introduction: Pentavalent antimonials are the first drug of choice in the treatment of tegumentary leishmaniasis. Data on ototoxicity related with such drugs is scarcely available in literature, leading us to develop a study on cochleovestibular functions. Case Report: A case of a tegumentary leishmaniasis patient, a 78-year-old man who presented a substantial increase in auditory threshold with tinnitus and severe rotatory dizziness during the treatment with meglumine antimoniate, is reported. These symptoms worsened in two weeks after treatment was interrupted. Conclusion: Dizziness and tinnitus had already been related to meglumine antimoniate. However, this is the first well documented case of cochlear-vestibular toxicity related to meglumine antimoniate. PMID:25229226

  8. First report on ototoxicity of meglumine antimoniate.

    PubMed

    Valete-Rosalino, Cláudia Maria; Araujo-Melo, Maria Helena; Bezerra, Débora Cristina de Oliveira; Barcelos, Renata Oliveira de; Melo-Ferreira, Vanessa de; Torraca, Tânia Salgado de Sousa; Martins, Ana Cristina da Costa; Moreira, João Soares; Vargas, Mirian Catherine Melgares; Braga, Frederico Pereira Bom; Salgueiro, Mariza de Matos; Saheki, Maurício Naoto; Schubach, Armando Oliveira

    2014-01-01

    Pentavalent antimonials are the first drug of choice in the treatment of tegumentary leishmaniasis. Data on ototoxicity related with such drugs is scarcely available in literature, leading us to develop a study on cochleovestibular functions. A case of a tegumentary leishmaniasis patient, a 78-year-old man who presented a substantial increase in auditory threshold with tinnitus and severe rotatory dizziness during the treatment with meglumine antimoniate, is reported. These symptoms worsened in two weeks after treatment was interrupted. Dizziness and tinnitus had already been related to meglumine antimoniate. However, this is the first well documented case of cochlear-vestibular toxicity related to meglumine antimoniate.

  9. Inhibition of renal caveolin-1 reduces natriuresis and produces hypertension in sodium-loaded rats

    PubMed Central

    Gildea, John J.; Kemp, Brandon A.; Howell, Nancy L.; Van Sciver, Robert E.; Carey, Robert M.

    2011-01-01

    Renal dopamine receptor function and ion transport inhibition are impaired in essential hypertension. We recently reported that caveolin-1 (CAV1) and lipid rafts are necessary for normal D1-like receptor-dependent internalization of Na-K-ATPase in human proximal tubule cells. We now hypothesize that CAV1 is necessary for the regulation of urine sodium (Na+) excretion (UNaV) and mean arterial blood pressure (MAP) in vivo. Acute renal interstitial (RI) infusion into Sprague-Dawley rats of 1 μg·kg−1·min−1 fenoldopam (FEN; D1-like receptor agonist) caused a 0.46 ± 0.15-μmol/min increase in UNaV (over baseline of 0.29 ± 0.04 μmol/min; P < 0.01). This increase was seen in Na+-loaded rats, but not in those under a normal-sodium load. Coinfusion with β-methyl cyclodextrin (βMCD; lipid raft disrupter, 200 μg·kg−1·min−1) completely blocked this FEN-induced natriuresis (P < 0.001). Long-term (3 day) lipid raft disruption via continuous RI infusion of 80 μg·kg−1·min−1 βMCD decreased renal cortical CAV1 expression (47.3 ± 6.4%; P < 0.01) and increased MAP (32.4 ± 6.6 mmHg; P < 0.001) compared with vehicle-infused animals. To determine whether the MAP rise was due to a CAV1-dependent lipid raft-mediated disruption, Na+-loaded rats were given a bolus RI infusion of CAV1 siRNA. Two days postinfusion, cortical CAV1 expression was decreased by 73.6 ± 8.2% (P < 0.001) and the animals showed an increase in MAP by 17.4 ± 2.9 mmHg (P < 0.01) compared with animals receiving scrambled control siRNA. In summary, acute kidney-specific lipid raft disruption decreases CAV1 expression and blocks D1-like receptor-induced natriuresis. Furthermore, chronic disruption of lipid rafts or CAV1 protein expression in the kidney induces hypertension. PMID:21289050

  10. Inhibition of renal caveolin-1 reduces natriuresis and produces hypertension in sodium-loaded rats.

    PubMed

    Gildea, John J; Kemp, Brandon A; Howell, Nancy L; Van Sciver, Robert E; Carey, Robert M; Felder, Robin A

    2011-04-01

    Renal dopamine receptor function and ion transport inhibition are impaired in essential hypertension. We recently reported that caveolin-1 (CAV1) and lipid rafts are necessary for normal D(1)-like receptor-dependent internalization of Na-K-ATPase in human proximal tubule cells. We now hypothesize that CAV1 is necessary for the regulation of urine sodium (Na(+)) excretion (U(Na)V) and mean arterial blood pressure (MAP) in vivo. Acute renal interstitial (RI) infusion into Sprague-Dawley rats of 1 μg·kg⁻¹·min⁻¹ fenoldopam (FEN; D(1)-like receptor agonist) caused a 0.46 ± 0.15-μmol/min increase in U(Na)V (over baseline of 0.29 ± 0.04 μmol/min; P < 0.01). This increase was seen in Na(+)-loaded rats, but not in those under a normal-sodium load. Coinfusion with β-methyl cyclodextrin (βMCD; lipid raft disrupter, 200 μg·kg⁻¹·min⁻¹) completely blocked this FEN-induced natriuresis (P < 0.001). Long-term (3 day) lipid raft disruption via continuous RI infusion of 80 μg·kg⁻¹·min⁻¹ βMCD decreased renal cortical CAV1 expression (47.3 ± 6.4%; P < 0.01) and increased MAP (32.4 ± 6.6 mmHg; P < 0.001) compared with vehicle-infused animals. To determine whether the MAP rise was due to a CAV1-dependent lipid raft-mediated disruption, Na(+)-loaded rats were given a bolus RI infusion of CAV1 siRNA. Two days postinfusion, cortical CAV1 expression was decreased by 73.6 ± 8.2% (P < 0.001) and the animals showed an increase in MAP by 17.4 ± 2.9 mmHg (P < 0.01) compared with animals receiving scrambled control siRNA. In summary, acute kidney-specific lipid raft disruption decreases CAV1 expression and blocks D(1)-like receptor-induced natriuresis. Furthermore, chronic disruption of lipid rafts or CAV1 protein expression in the kidney induces hypertension.

  11. Antimony leaching in plastics from waste electrical and electronic equipment (WEEE) with various acids and gamma irradiation.

    PubMed

    Tostar, Sandra; Stenvall, Erik; Boldizar, Antal; Foreman, Mark R St J

    2013-06-01

    There has been a recent interest in antimony since the availability in readily mined areas is decreasing compared to the amounts used. It is important in many applications such as flame retardants and in the production of polyester, which can trigger an investigation of the leachability of antimony from plastics using different acids. In this paper, different types of acids are tested for their ability to leach antimony from a discarded computer housing, made of poly(acrylonitrile butadiene styrene), which is a common plastic type used in electrical and electronic equipment. The acid solutions included sodium hydrogen tartrate (0.5M) dissolved in either dimethyl sulfoxide or water (at ca. 23°C and heated to ca. 105°C). The metal content after leaching was determined by inductively coupled plasma optical emission spectroscopy. The most efficient leaching medium was the heated solution of sodium hydrogen tartrate in dimethyl sulfoxide, which leached almost half of the antimony from the poly(acrylonitrile butadiene styrene). Gamma irradiation, which is proposed to improve the mechanical properties in plastics, was used here to investigate the influence of antimony leaching ability. No significant change in the amount of leached antimony could be observed.

  12. Catalytic and inhibiting effects of lithium peroxide and hydroxide on sodium chlorate decomposition

    SciTech Connect

    Cannon, J.C.; Zhang, Y.

    1995-09-01

    Chemical oxygen generators based on sodium chlorate and lithium perchlorate are used in airplanes, submarines, diving, and mine rescue. Catalytic decomposition of sodium chlorate in the presence of cobalt oxide, lithium peroxide, and lithium hydroxide is studied using thermal gravimetric analysis. Lithium peroxide and hydroxide are both moderately active catalysts for the decomposition of sodium chlorate when used alone, and inhibitors when used with the more active catalyst cobalt oxide.

  13. Sodium sulphite inhibition of potato and cherry polyphenolics in nucleic acid extraction for virus detection by RT-PCR.

    PubMed

    Singh, R P; Nie, X; Singh, M; Coffin, R; Duplessis, P

    2002-01-01

    Phenolic compounds from plant tissues inhibit reverse transcription-polymerase chain reaction (RT-PCR). Multiple-step protocols using several additives to inhibit polyphenolic compounds during nucleic acid extraction are common, but time consuming and laborious. The current research highlights that the inclusion of 0.65 to 0.70% of sodium sulphite in the extraction buffer minimizes the pigmentation of nucleic acid extracts and improves the RT-PCR detection of Potato virus Y (PVY) and Potato leafroll virus (PLRV) in potato (Solanum tuberosum) tubers and Prune dwarf virus (PDV) and Prunus necrotic ringspot virus (PNRSV) in leaves and bark in the sweet cherry (Prunus avium) tree. Substituting sodium sulphite in the nucleic acid extraction buffer eliminated the use of proteinase K during extraction. Reagents phosphate buffered saline (PBS)-Tween 20 and polyvinylpyrrolidone (PVP) were also no longer required during RT or PCR phase. The resultant nucleic acid extracts were suitable for both duplex and multiplex RT-PCR. This simple and less expensive nucleic acid extraction protocol has proved very effective for potato cv. Russet Norkotah, which contains a high amount of polyphenolics. Comparing commercially available RNA extraction kits (Catrimox and RNeasy), the sodium sulphite based extraction protocol yielded two to three times higher amounts of RNA, while maintaining comparable virus detection by RT-PCR. The sodium sulphite based extraction protocol was equally effective in potato tubers, and in leaves and bark from the cherry tree.

  14. Inhibition of vacuolation toxin activity of Helicobacter pylori by iodine, nitrite and potentiation by sodium chloride, sterigmatocystin and fluoride.

    PubMed

    Ma, Fengjuan; Zhao, Wenyuan; Kudo, Masanobu; Aoki, Kazuo; Misumi, Junichi

    2002-10-01

    The toxin VacA produced by Helicobacter pylori is an important determinant of virulence. VacA causes vacuolation of cultured cells such as HeLa cells. Iodine, nitrite, sodium chloride, thiocyanate and fungus toxin sterigmatocystin are universally present in nature and could possibly be related to carcinogenesis of the stomach. The present study was designed to examine the effects of the above-mentioned compound on VacA-induced vacuolation of HeLa cells, which was quantitated using the neutral red uptake assay. VacA-induced vacuolation was inhibited by BafA1 and NPPB. Formation of large vacuoles was inhibited in the presence of iodine, nitrite, but enhanced by sodium chloride, thiocyanate, fluoride and sterigmatocystin. Our results indicate that VacA toxin may interact with other gastric cancer risk factors present naturally in the environment, and suggest that those compounds may modulate the development of gastric cancer induced by H. pylori.

  15. Participation of α2‐adrenoceptors in sodium appetite inhibition during sickness behaviour following administration of lipopolysaccharide

    PubMed Central

    Almeida, Roberto L.; David, Richard B.; de Paula, Patricia M.; Andrade, Carina A. F.; Menani, José V.

    2015-01-01

    Abstract Sickness behaviour, a syndrome characterized by a general reduction in animal activity, is part of the active‐phase response to fight infection. Lipopolysaccharide (LPS), an effective endotoxin to model sickness behaviour, reduces thirst and sodium excretion, and increases neurohypophysial secretion. Here we review the effects of LPS on thirst and sodium appetite. Altered renal function and hydromineral fluid intake in response to LPS occur in the context of behavioural reorganization, which manifests itself as part of the syndrome. Recent data show that, in addition to its classical effect on thirst, non‐septic doses of LPS injected intraperitoneally produce a preferential inhibition of intracellular thirst versus extracellular thirst. Moreover, LPS also reduced hypertonic NaCl intake in sodium‐depleted rats that entered a sodium appetite test. Antagonism of α2‐adrenoceptors abolished the effect of LPS on sodium appetite. LPS and cytokine transduction potentially recruit brain noradrenaline and α2‐adrenoceptors to control sodium appetite and sickness behaviour. PMID:26036817

  16. Protective Role of Sodium-Glucose Co-Transporter 2 Inhibition Against Vascular Complications in Diabetes.

    PubMed

    Yamagishi, Sho-ichi; Matsui, Takanori

    2016-04-01

    Diabetic micro- and macroangiopathy are devastating vascular complications that could account for disabilities and high mortality rate in patients with diabetes. Indeed, diabetic nephropathy and retinopathy are the leading causes of end-stage renal failure and acquired blindness, respectively, and atherosclerotic cardiovascular diseases (CVD) accounts for about 60% of death in diabetic subjects. As a result, the average life span of diabetic patients is about 10-15 years shorter than that of non-diabetic subjects. Furthermore, tight blood glucose control might have no more than a marginal impact on CVD in general and on all-cause mortality in particular in diabetes. Therefore, therapeutic strategies that target vascular complications in diabetes need to be developed. Recently, selective inhibition of sodium-glucose co-transporter 2 (SGLT2) has been proposed as a potential therapeutic target for the treatment of patients with diabetes because of low risk of hypoglycemia and no weight gain. Because 90% of glucose filtered by the glomerulus is reabsorbed by a low-affinity/high-capacity SGLT2 expressed in the S1 and S2 segments of the proximal tubule, blockade of SGLT2 promotes urinary glucose excretion and as a result improves hyperglycemia in an insulin-independent manner. Moreover, we have shown that SGLT2-mediated glucose overload to tubular cells could elicit inflammatory and pro-apoptotic reactions in this cell, being directly involved in diabetic nephropathy. In addition, several clinical studies have also shown that SGLT2 inhibitors could reduce blood pressure, body weight, and serum uric acid levels and ameliorate cardiovascular risk in patients with diabetes. This review summarizes the pathophysiological role of SGLT2 in vascular complications in diabetes and its potential therapeutic interventions.

  17. Ranolazine inhibits voltage-gated mechanosensitive sodium channels in human colon circular smooth muscle cells

    PubMed Central

    Neshatian, Leila; Strege, Peter R.; Rhee, Poong-Lyul; Kraichely, Robert E.; Mazzone, Amelia; Bernard, Cheryl E.; Cima, Robert R.; Larson, David W.; Dozois, Eric J.; Kline, Crystal F.; Mohler, Peter J.; Beyder, Arthur

    2015-01-01

    Human jejunum smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs) express the SCN5A-encoded voltage-gated, mechanosensitive sodium channel NaV1.5. NaV1.5 contributes to small bowel excitability, and NaV1.5 inhibitor ranolazine produces constipation by an unknown mechanism. We aimed to determine the presence and molecular identity of Na+ current in the human colon smooth muscle and to examine the effects of ranolazine on Na+ current, mechanosensitivity, and smooth muscle contractility. Inward currents were recorded by whole cell voltage clamp from freshly dissociated human colon SMCs at rest and with shear stress. SCN5A mRNA and NaV1.5 protein were examined by RT-PCR and Western blots, respectively. Ascending human colon strip contractility was examined in a muscle bath preparation. SCN5A mRNA and NaV1.5 protein were identified in human colon circular muscle. Freshly dissociated human colon SMCs had Na+ currents (−1.36 ± 0.36 pA/pF), shear stress increased Na+ peaks by 17.8 ± 1.8% and accelerated the time to peak activation by 0.7 ± 0.3 ms. Ranolazine (50 μM) blocked peak Na+ current by 43.2 ± 9.3% and inhibited shear sensitivity by 25.2 ± 3.2%. In human ascending colon strips, ranolazine decreased resting tension (31%), reduced the frequency of spontaneous events (68%), and decreased the response to smooth muscle electrical field stimulation (61%). In conclusion, SCN5A-encoded NaV1.5 is found in human colonic circular smooth muscle. Ranolazine blocks both peak amplitude and mechanosensitivity of Na+ current in human colon SMCs and decreases contractility of human colon muscle strips. Our data provide a likely mechanistic explanation for constipation induced by ranolazine. PMID:26185330

  18. Inhibition of biosynthesis of metalloprotease of Aeromonas sobria by sodium chloride in the medium.

    PubMed

    Takahashi, Eizo; Kobayashi, Hidetomo; Yamanaka, Hiroyasu; Nair, Gopinath Balakrish; Takeda, Yoshifumi; Arimoto, Sakae; Negishi, Tomoe; Okamoto, Keinosuke

    2011-01-01

    The present authors have previously shown that the serine protease activity of Aeromonas sobria is markedly decreased when A. sobria is cultured in medium containing 3.0% sodium chloride (NaCl, concentration almost equivalent to sea water salinity), and that this occurs because, although the synthesis of ASP is not disturbed by the salt in the medium, the maturation pathway of serine protease of A. sobria (ASP) does not proceed successfully in such a medium. In this study, the effect of salt in the medium on the production of metalloprotease by A. sobria (AMP) was examined. A. sobria produced AMP in the milieu when the bacteria were cultured in medium containing (NaCl) at a concentration of 0.5%. However, AMP was not produced when the bacteria were cultured in salty medium containing 1.5% or more NaCl. To examine how NaCl reduces the production of metalloprotease by A. sobria, the amount of amp mRNA in the cell was measured and it was found that this decreased in proportion to the concentration of NaCl in the medium. The mRNA of amp was not detected in cells cultured in medium containing 1.5% or more NaCl. This means that the transcription of amp is inhibited in salty condition. As described, NaCl in the medium disturbs the maturation pathway of ASP. The mode of action whereby NaCl suppresses AMP activity in A. sobria differs from the mechanism for suppressing ASP activity. © 2010 The Societies and Blackwell Publishing Asia Pty Ltd.

  19. Garlic oil inhibits dextran sodium sulfate-induced ulcerative colitis in rats.

    PubMed

    Balaha, Mohamed; Kandeel, Samah; Elwan, Walaa

    2016-02-01

    Garlic oil (GO) is used for centuries in folk medicine as a therapy for many diseases including inflammatory disorders. Recently, it has exhibited potent anti-oxidant, anti-inflammatory and immunomodulatory effects. Consequently, we evaluated the possible protective effect of GO in a rat model of colitis, induced by dextran sulfate sodium (DSS). Colitis induced by allowing rats a free access to drinking water containing 5% DSS for 7 days, from day 1 to day 7. GO was administered orally in doses of 25, 50 and 100mg/kg/day. Mesalazine used as a standard medication in a dose of 15 mg/kg/day. All animals fasted for 2h, 1h before and 1h after giving the treatment, which introduced daily for 7 days, from day 1 to day 7, at 10:00 to 11:00 A.M. Animal body, and colonic weights, colonic myeloperoxidase (MPO), and superoxide dismutase (SOD) activities, colonic reduced-glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-10 levels, macroscopic and microscopic changes of colonic tissues were evaluated. GO treatment significantly suppressed the elevated colonic weight, MPO activity, MDA, TNF-α and IL-1β levels. However, it potentiated the decrease body weight, colonic SOD activity, GSH and IL-10 levels. Moreover, it ameliorated the marked macroscopic and microscopic changes of colonic mucosa in a dose dependent manner. Garlic oil inhibits DSS-induced colitis in rats may be through its anti-oxidant, anti-inflammatory and immunomodulatory properties. Therefore, GO could be a promising protective agent recommended for UC patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Mechanism of inhibition by chlorpromazine of the human pain threshold sodium channel, Nav1.7.

    PubMed

    Lee, Su-Jin; Kim, Dong-Hyun; Hahn, Sang June; Waxman, Stephen G; Choi, Jin-Sung

    2017-02-03

    Chlorpromazine is a phenothiazine derivative which is primarily used for schizophrenia and occasionally for migraine. Because Nav1.7 plays an important role in pain sensation, we investigated whether chlorpromazine blocks the human Nav1.7 (hNav1.7) sodium current in HEK293 cells stably expressing hNav1.7 using the whole-cell patch-clamp technique. The peak current of hNav1.7 was reduced by chlorpromazine in a concentration-dependent manner with a half-maximal inhibitory concentration of 25.9±0.6μM and a Hill coefficient of 2.3±0.1. The calmodulin inhibitory peptide did not abolish the blockade of hNav1.7 currents by chlorpromazine. The blockade of hNav1.7 currents by chlorpromazine was completely and repeatedly reversible after washout. The half-maximal voltage of activation of hNav1.7 was not changed by chlorpromazine. However, chlorpromazine caused hyperpolarized the steady-state inactivation of hNav1.7. The recovery from inactivation in the presence of chlorpromazine was slower than in the absence of chlorpromazine. Chlorpromazine also showed strong use-dependent inhibition of the hNav1.7 current. Our results demonstrate that chlorpromazine blocks the hNav1.7 current in concentration-, state- and use-dependent manners and suggest that it merits further study for potential use in pain management.

  1. Stage-Specific Activity of Pentavalent Antimony against Leishmania donovani Axenic Amastigotes

    PubMed Central

    Ephros, Moshe; Bitnun, Ari; Shaked, Pninit; Waldman, Ella; Zilberstein, Dan

    1999-01-01

    The standard treatment of human visceral leishmaniasis involves the use of pentavalent antimony (SbV) compounds. In recent years increasing numbers of clinical failures of treatment with SbV have been reported, probably due to the development of parasite resistance to this compound. The mode of action and mechanisms of resistance to SbV have not been fully elucidated. In the present study an axenic amastigote culture was used to study the in vitro responses of Leishmania donovani to SbV. Susceptibility to both sodium stibogluconate and meglumine antimoniate was found to be stage specific. Amastigotes were 73 to 271 times more susceptible to SbV than were promastigotes. As opposed to SbV, trivalent antimony (SbIII) was similarly toxic to both developmental stages. When promastigotes were transformed to amastigotes, susceptibility to meglumine antimoniate developed after 4 to 5 days, upon the completion of differentiation. In contrast, with transformation from amastigotes to promastigotes, resistance to meglumine antimoniate was acquired rapidly, within 24 h, before the completion of differentiation. The culture of promastigotes at an acidic pH (5.5) or at an elevated temperature (37°C) alone did not lead to the appearance of SbV susceptibility, emphasizing the requirement of both these environmental factors for the development of SbV susceptibility. A previously isolated sodium stibogluconate (Pentostam)-resistant L. donovani mutant (Ld1S.20) is also resistant to meglumine antimoniate, indicating cross-resistance to SbV-containing compounds. In contrast, no cross-resistance was found with SbIII, suggesting a mechanism of SbV resistance different from that described in Leishmania tarentolae. These data show that L. donovani susceptibility to SbV is parasite intrinsic, stage specific, and macrophage independent. PMID:9925518

  2. Copper-promoted cementation of antimony in hydrochloric acid system: A green protocol.

    PubMed

    Wu, Lian-Kui; Li, Ying-Ying; Cao, Hua-Zhen; Zheng, Guo-Qu

    2015-12-15

    A new method of recovering antimony in hydrochloric acid system by cementation with copper powder was proposed and carried out at laboratory scale. Thermodynamic analysis and cyclic voltammetry test were conducted to study the cementation process. This is a novel antimony removal technology and quite meets the requirements of green chemistry. The main cement product Cu2Sb is a promising anodic material for lithium and sodium ion battery. And nearly all consumed copper powder are transformed into CuCl which is an important industrial material. The effect of reaction temperature, stoichiometric ratio of Cu to Sb(III), stirring rate and concentration of HCl on the cementation efficiency of antimony were investigated in detail. Optimized cementation condition is obtained at 60 °C for 120 min and stirring rate of 600 rpm with Cu/Sb(III) stoichiometric ratio of 6 in 3 mol L(-1) HCl. At this time, nearly all antimony can be removed by copper powder and the cementation efficiency is over 99%. The structure and morphologies of the cement products were characterized by X-ray diffraction and scanning electron microscopy, respectively. Results show that the reaction temperature has little influence on the morphology of the cement products which consist of particles with various sizes. The activation energy of the cementation antimony on copper is 37.75 kJ mol(-1), indicating a chemically controlled step. Inductively coupled plasma mass spectrometry results show that no stibine generates during the cementation process.

  3. Mineral resource of the month: antimony

    USGS Publications Warehouse

    ,

    2008-01-01

    The article describes the characteristics and industrial uses of antimony. Antimony, which is produced as a byproduct of mining other metals such as gold, lead or silver, is used in everything from flame retardants, batteries, ceramics and glass. It is also used in glass for television picture tubes, computer monitors, pigments and catalysts.

  4. Heteronuclear compounds of arsenic and antimony

    NASA Astrophysics Data System (ADS)

    Mauser, James E.

    1982-09-01

    Volatilization of secondary metals such as arsenic, antimony, and bismuth, during the smelting of copper ores, is important because of environmental and resource considerations. The Bureau of Mines, United States Department of the Interior, has been studying copper concentrate roasting in conjunction with the volatility of these minor constituents. Some unusual vaporization behavior initiated this supplemental paper which shows that when the mixed sulfides of arsenic and antimony are heated, the volatilization of arsenic is retarded and the volatilization of antimony increased. Mixed oxides of arsenic and antimony also exhibit exceptional volatilization behavior. These anomalous vaporization behaviors are attributed to the formation of heteronuclear compounds of arsenic and antimony, but the colligative properties of solutions may also be a factor.

  5. Inhibition of tetrodotoxin-resistant sodium current in dorsal root ganglia neurons mediated by D1/D5 dopamine receptors

    PubMed Central

    2013-01-01

    Background Dopaminergic fibers originating from area A11 of the hypothalamus project to different levels of the spinal cord and represent the major source of dopamine. In addition, tyrosine hydroxylase, the rate-limiting enzyme for the synthesis of catecholamines, is expressed in 8-10% of dorsal root ganglia (DRG) neurons, suggesting that dopamine may be released in the dorsal root ganglia. Dopamine has been shown to modulate calcium current in DRG neurons, but the effects of dopamine on sodium current and on the firing properties of small DRG neurons are poorly understood. Results The effects of dopamine and dopamine receptor agonists were tested on the tetrodotoxin-resistant (TTX-R) sodium current recorded from acutely dissociated small (diameter ≤ 25 μm) DRG neurons. Dopamine (20 μM) and SKF 81297 (10 μM) caused inhibition of TTX-R sodium current in small DRG neurons by 23% and 37%, respectively. In contrast, quinpirole (20 μM) had no effects on the TTX-R sodium current. Inhibition by SKF 81297 of the TTX-R sodium current was not affected when the protein kinase A (PKA) activity was blocked with the PKA inhibitory peptide (6–22), but was greatly reduced when the protein kinase C (PKC) activity was blocked with the PKC inhibitory peptide (19–36), suggesting that activation of D1/D5 dopamine receptors is linked to PKC activity. Expression of D1and D5 dopamine receptors in small DRG neurons, but not D2 dopamine receptors, was confirmed by Western blotting and immunofluorescence analysis. In current clamp experiments, the number of action potentials elicited in small DRG neurons by current injection was reduced by ~ 30% by SKF 81297. Conclusions We conclude that activation of D1/D5 dopamine receptors inhibits TTX-R sodium current in unmyelinated nociceptive neurons and dampens their intrinsic excitability by reducing the number of action potentials in response to stimulus. Increasing or decreasing levels of dopamine in the dorsal root ganglia

  6. 21 CFR 862.3110 - Antimony test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Antimony test system. 862.3110 Section 862.3110....3110 Antimony test system. (a) Identification. An antimony test system is a device intended to measure antimony, a heavy metal, in urine, blood, vomitus, and stomach contents. Measurements obtained by this...

  7. 21 CFR 862.3110 - Antimony test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Antimony test system. 862.3110 Section 862.3110....3110 Antimony test system. (a) Identification. An antimony test system is a device intended to measure antimony, a heavy metal, in urine, blood, vomitus, and stomach contents. Measurements obtained by this...

  8. 21 CFR 862.3110 - Antimony test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Antimony test system. 862.3110 Section 862.3110....3110 Antimony test system. (a) Identification. An antimony test system is a device intended to measure antimony, a heavy metal, in urine, blood, vomitus, and stomach contents. Measurements obtained by this...

  9. Alkali oxide-tantalum, niobium and antimony oxide ionic conductors

    NASA Technical Reports Server (NTRS)

    Roth, R. S.; Brower, W. S.; Parker, H. S.; Minor, D. B.; Waring, J. L.

    1975-01-01

    The phase equilibrium relations of four systems were investigated in detail. These consisted of sodium and potassium antimonates with antimony oxide and tantalum and niobium oxide with rubidium oxide as far as the ratio 4Rb2O:llB2O5 (B=Nb, Ta). The ternary system NaSbO3-Sb2O4-NaF was investigated extensively to determine the actual composition of the body centered cubic sodium antimonate. Various other binary and ternary oxide systems involving alkali oxides were examined in lesser detail. The phases synthesized were screened by ion exchange methods to determine mobility of the mobility of the alkali ion within the niobium, tantalum or antimony oxide (fluoride) structural framework. Five structure types warranted further investigation; these structure types are (1) hexagonal tungsten bronze (HTB), (2) pyrochlore, (3) the hybrid HTB-pyrochlore hexagonal ordered phases, (4) body centered cubic antimonates and (5) 2K2O:3Nb2O5. Although all of these phases exhibit good ion exchange properties only the pyrochlore was prepared with Na(+) ions as an equilibrium phase and as a low porosity ceramic. Sb(+3) in the channel interferes with ionic conductivity in this case, although relatively good ionic conductivity was found for the metastable Na(+) ion exchanged analogs of RbTa2O5F and KTaWO6 pyrochlore phases.

  10. [Inhibition of the sodium inactivation of the nodal membrane by anemonia sulcata toxin II].

    PubMed

    Bergman, C; Dubois, J M; Rojas, E; Rathmayer, W

    1976-05-31

    A neurotoxin (ATX-II) extracted from the tentacles of Anemonia sulcata has been found to interact with the sodium channel of the nodal membrane in myelinated nerve fibres from Rana esculenta. If externally applied at low concentration (Kd = 20 muM), it reduces considerably the rate of inactivation of the sodium conductance without affecting the activation. At such concentrations, the potassium conductance is not affected. If internally applied ATX-II does not affect the membrane conductance.

  11. Sodium phenylacetate inhibits adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice at multiple steps.

    PubMed

    Dasgupta, Subhajit; Zhou, You; Jana, Malabendu; Banik, Naren L; Pahan, Kalipada

    2003-04-01

    Experimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. The present study underlines the importance of sodium phenylacetate (NaPA), a drug approved for urea cycle disorders, in inhibiting the disease process of adoptively transferred EAE in female SJL/J mice at multiple steps. Myelin basic protein (MBP)-primed T cells alone induced the expression of NO synthase (iNOS) and the activation of NF-kappaB in mouse microglial cells through cell-cell contact. However, pretreatment of MBP-primed T cells with NaPA markedly inhibited its ability to induce microglial expression of iNOS and activation of NF-kappaB. Consistently, adoptive transfer of MBP-primed T cells, but not that of NaPA-pretreated MBP-primed T cells, induced the clinical symptoms of EAE in female SJL/J mice. Furthermore, MBP-primed T cells isolated from NaPA-treated donor mice were also less efficient than MBP-primed T cells isolated from normal donor mice in inducing iNOS in microglial cells and transferring EAE to recipient mice. Interestingly, clinical symptoms of EAE were much less in mice receiving NaPA through drinking water than those without NaPA. Similar to NaPA, sodium phenylbutyrate, a chemically synthesized precursor of NaPA, also inhibited the disease process of EAE. Histological and immunocytochemical analysis showed that NaPA inhibited EAE-induced spinal cord mononuclear cell invasion and normalized iNOS, nitrotyrosine, and p65 (the RelA subunit of NF-kappaB) expression within the spinal cord. Taken together, our results raise the possibility that NaPA or sodium phenylbutyrate taken through drinking water or milk may reduce the observed neuroinflammation and disease process in multiple sclerosis patients.

  12. Ranolazine inhibits voltage-gated mechanosensitive sodium channels in human colon circular smooth muscle cells.

    PubMed

    Neshatian, Leila; Strege, Peter R; Rhee, Poong-Lyul; Kraichely, Robert E; Mazzone, Amelia; Bernard, Cheryl E; Cima, Robert R; Larson, David W; Dozois, Eric J; Kline, Crystal F; Mohler, Peter J; Beyder, Arthur; Farrugia, Gianrico

    2015-09-15

    Human jejunum smooth muscle cells (SMCs) and interstitial cells of Cajal (ICCs) express the SCN5A-encoded voltage-gated, mechanosensitive sodium channel NaV1.5. NaV1.5 contributes to small bowel excitability, and NaV1.5 inhibitor ranolazine produces constipation by an unknown mechanism. We aimed to determine the presence and molecular identity of Na(+) current in the human colon smooth muscle and to examine the effects of ranolazine on Na(+) current, mechanosensitivity, and smooth muscle contractility. Inward currents were recorded by whole cell voltage clamp from freshly dissociated human colon SMCs at rest and with shear stress. SCN5A mRNA and NaV1.5 protein were examined by RT-PCR and Western blots, respectively. Ascending human colon strip contractility was examined in a muscle bath preparation. SCN5A mRNA and NaV1.5 protein were identified in human colon circular muscle. Freshly dissociated human colon SMCs had Na(+) currents (-1.36 ± 0.36 pA/pF), shear stress increased Na(+) peaks by 17.8 ± 1.8% and accelerated the time to peak activation by 0.7 ± 0.3 ms. Ranolazine (50 μM) blocked peak Na(+) current by 43.2 ± 9.3% and inhibited shear sensitivity by 25.2 ± 3.2%. In human ascending colon strips, ranolazine decreased resting tension (31%), reduced the frequency of spontaneous events (68%), and decreased the response to smooth muscle electrical field stimulation (61%). In conclusion, SCN5A-encoded NaV1.5 is found in human colonic circular smooth muscle. Ranolazine blocks both peak amplitude and mechanosensitivity of Na(+) current in human colon SMCs and decreases contractility of human colon muscle strips. Our data provide a likely mechanistic explanation for constipation induced by ranolazine. Copyright © 2015 the American Physiological Society.

  13. Transformation/dissolution examination of antimony and antimony compounds with speciation of the transformation/dissolution solutions.

    PubMed

    Skeaff, James M; Beaudoin, Robert; Wang, Ruiping; Joyce, Barry

    2013-01-01

    Speciation is held to be a key factor in controlling the ecotoxicity of metals in solution. Using the United Nations transformation/dissolution protocol (T/DP) for metals and sparingly soluble metal compounds, we have examined the transformation/dissolution (T/D) characteristics in terms of the concentrations of total dissolved Sb at pH 6 and 8.5 in 1, 10, and 100 mg/L loadings over 7 d as well as the concentrations of Sb(III) and Sb(V) at the 1 mg/L loadings over 28 d, of sodium hexahydroxoantimonate (NaSb(OH)(6)), antimony metal (Sb), antimony trioxide (Sb(2) O(3)), antimony sulfide (Sb(2) S(3)), sodium antimonate (NaSbO(3)), antimony tris(ethylene glycolate) (Sb(2) (C(2) H(4) O(2) )(3)), antimony trichloride (SbCl(3)), antimony triacetate (Sb(CH(3) COO)(3)), and antimony pentoxide (Sb(2) O(5) ). We also measured the concentrations of the dissolved Sb(III) and Sb(V) species at the 1 mg/L loadings. Because of complexing, the trivalent organic Sb compounds exhibited little or no oxidation of Sb(III) to Sb(V). However, oxidation of Sb(III) to Sb(V) was evident for the trivalent inorganic Sb compounds. Conversely, with pentavalent Sb compounds, there was no reduction of Sb(V) to Sb(III). Based on the percentage of Sb in the compound dissolved or metal reacted at 28 d and 1 mg/L loadings, the solubility rankings at pH 6 are NaSb(OH)(6)  > Sb(CH(3) COO)(3)  > Sb metal > Sb(2) (C(2) H(4) O(2))(3)  > Sb(2) S(3)  > Sb(2) O(3)  > NaSbO(3)  ≈ SbCl(3)  > Sb(2) O(5). For pH 8.5 the order is NaSb(OH)(6)  > Sb(CH(3) COO)(3)  > Sb metal > Sb(2) (C(2) H(4) O(2) )(3)  > SbCl(3)  > Sb(2) O(3)  > Sb(2) S(3)  > NaSbO(3)  > Sb(2) O(5) . We provide worked examples of how the T/D data have been used to derive hazard classification proposals for Sb metal and these selected compounds for submission to the European Chemicals Agency under the Registration, Evaluation, Authorization and Restriction of CHemicals (REACH

  14. Moderate dietary sodium restriction added to angiotensin converting enzyme inhibition compared with dual blockade in lowering proteinuria and blood pressure: randomised controlled trial.

    PubMed

    Slagman, Maartje C J; Waanders, Femke; Hemmelder, Marc H; Woittiez, Arend-Jan; Janssen, Wilbert M T; Lambers Heerspink, Hiddo J; Navis, Gerjan; Laverman, Gozewijn D

    2011-07-26

    To compare the effects on proteinuria and blood pressure of addition of dietary sodium restriction or angiotensin receptor blockade at maximum dose, or their combination, in patients with non-diabetic nephropathy receiving background treatment with angiotensin converting enzyme (ACE) inhibition at maximum dose. Multicentre crossover randomised controlled trial. Outpatient clinics in the Netherlands. 52 patients with non-diabetic nephropathy. All patients were treated during four 6 week periods, in random order, with angiotensin receptor blockade (valsartan 320 mg/day) or placebo, each combined with, consecutively, a low sodium diet (target 50 mmol Na(+)/day) and a regular sodium diet (target 200 mmol Na(+)/day), with a background of ACE inhibition (lisinopril 40 mg/day) during the entire study. The drug interventions were double blind; the dietary interventions were open label. The primary outcome measure was proteinuria; the secondary outcome measure was blood pressure. Mean urinary sodium excretion, a measure of dietary sodium intake, was 106 (SE 5) mmol Na(+)/day during a low sodium diet and 184 (6) mmol Na(+)/day during a regular sodium diet (P<0.001). Geometric mean residual proteinuria was 1.68 (95% confidence interval 1.31 to 2.14) g/day during ACE inhibition plus a regular sodium diet. Addition of angiotensin receptor blockade to ACE inhibition reduced proteinuria to 1.44 (1.07 to 1.93) g/day (P=0.003), addition of a low sodium diet reduced it to 0.85 (0.66 to 1.10) g/day (P<0.001), and addition of angiotensin receptor blockade plus a low sodium diet reduced it to 0.67 (0.50 to 0.91) g/day (P<0.001). The reduction of proteinuria by the addition of a low sodium diet to ACE inhibition (51%, 95% confidence interval 43% to 58%) was significantly larger (P<0.001) than the reduction of proteinuria by the addition of angiotensin receptor blockade to ACE inhibition (21%, (8% to 32%) and was comparable (P=0.009, not significant after Bonferroni correction) to the

  15. Phloridzin inhibits high K+-induced contraction via the inhibition of sodium: glucose cotransporter 1 in rat ileum

    PubMed Central

    KANDA, Hidenori; KANEDA, Takeharu; KAWAGUCHI, Akira; SASAKI, Noriyasu; TAJIMA, Tsuyoshi; URAKAWA, Norimoto; SHIMIZU, Kazumasa; SUZUKI, Hiroetsu

    2017-01-01

    Recent studies have shown that phloridzin, an inhibitor of sodium–glucose cotransporter (SGLT), strongly decreases high K+-induced contraction in phasic muscle, such as tenia coli, but slightly affects tonic muscle, such as trachea . In this study, we examined the inhibitory mechanism of phloridzin on high K+-induced muscle contraction in rat ileum, a phasic muscle. Phloridzin inhibited the high K+-induced contraction in the ileum and the aorta, and the relaxing effect of phloridzin at 1 mM in the ileum was approximately five-fold more potent than that in the aorta. The expression of SGLT1 mRNA in the ileum was higher than that of the aorta. Phloridzin significantly inhibited NADH/NAD ratio and phosphocreatine (PCr) content in the ileum; however, application of pyruvate recovered the inhibition of contraction and PCr content, but had no effect on ratio of NADH/NAD. High K+ increased 2-(N (7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake in ileal smooth muscle cells, and phloridzin inhibited the increase in a concentration-dependent manner. These results suggest that phloridzin inhibits high K+-induced contraction because of the inhibition of energy metabolism via the inhibition of SGLT1. PMID:28190822

  16. An Insight into Sodiation of Antimony from First-Principles Crystal Structure Prediction

    NASA Astrophysics Data System (ADS)

    Caputo, Riccarda

    2016-02-01

    Elemental antimony has recently become an attractive anode material for potential application in rechargeable sodium-ion batteries. I present a first-principles study of the structure-composition dependence of the Na-Sb system for both sodiation and desodiation processes. The enthalpy of reaction of x moles of sodium with the hexagonal structure of antimony reveals several stable crystal structures for 0 < x ≤ 3, with variable composition states for 1.25 < x < 2.75. The direct and reverse reactions pass through similar states in terms of enthalpy of formation and symmetry representation of the corresponding optimized structures, in particular for x = 1 and x = 3, confirming the two known phases, namely NaSb and Na3Sb. The calculations suggest that the optimal composition range for reversible sodiation of antimony is 1 < x ≤ 3, thus avoiding the global minimum at x = 1. This can help to rationalize the structure-composition dependence of the electrochemical performance of antimony in Na-ion batteries.

  17. Inhibition by pregnenolone sulphate, a metabolite of the neurosteroid pregnenolone, of voltage-gated sodium channels expressed in Xenopus oocytes.

    PubMed

    Horishita, Takafumi; Ueno, Susumu; Yanagihara, Nobuyuki; Sudo, Yuka; Uezono, Yasuhito; Okura, Dan; Sata, Takeyoshi

    2012-01-01

    Neurosteroids are known as allosteric modulators of the ligand-gated ion channel superfamily. Voltage-gated sodium channels (Na(v)) play an important role in mediating excitotoxic damages. Here we report the effects of neurosteroids on the function of Na(v), using voltage-clamp techniques in Xenopus oocytes expressed with the Na(v)1.2 α subunit. Pregnenolone sulphate, but not pregnenolone, inhibited sodium currents (I(Na)) at 3 - 100 μmol/L. The suppression of I(Na) by pregnenolone sulphate was due to increased inactivation with little change in activation. These findings suggest that pregnenolone sulphate, a metabolite of pregnenolone, suppresses the function of Na(v) via increased inactivation, which may contribute to the neuroprotection.

  18. Inhibition studies of soybean (Glycine max) urease with heavy metals, sodium salts of mineral acids, boric acid, and boronic acids.

    PubMed

    Kumar, Sandeep; Kayastha, Arvind M

    2010-10-01

    Various inhibitors were tested for their inhibitory effects on soybean urease. The K(i) values for boric acid, 4-bromophenylboronic acid, butylboronic acid, and phenylboronic acid were 0.20 +/- 0.05 mM, 0.22 +/- 0.04 mM, 1.50 +/- 0.10 mM, and 2.00 +/- 0.11 mM, respectively. The inhibition was competitive type with boric acid and boronic acids. Heavy metal ions including Ag(+), Hg(2+), and Cu(2+) showed strong inhibition on soybean urease, with the silver ion being a potent inhibitor (IC(50) = 2.3 x 10(-8) mM). Time-dependent inhibition studies exhibited biphasic kinetics with all heavy metal ions. Furthermore, inhibition studies with sodium salts of mineral acids (NaF, NaCl, NaNO(3), and Na(2)SO(4)) showed that only F(-) inhibited soybean urease significantly (IC(50) = 2.9 mM). Competitive type of inhibition was observed for this anion with a K(i) value of 1.30 mM.

  19. A randomized clinical trial to compare plaque inhibition of a sodium fluoride/potassium nitrate dentifrice versus a stabilized stannous fluoride/sodium hexametaphosphate dentifrice.

    PubMed

    Bellamy, Philip G; Khera, Nichelle; Day, Trevor N; Barker, Matthew L; Mussett, Andrew J

    2009-03-01

    To compare the plaque inhibition efficacy of a sodium fluoride/potassium nitrate (NaF/KNO3 with 1450 ppm F) test dentifrice to a 0.454% stannous fluoride/sodium hexametaphosphate/sodium fluoride positive control dentifrice (SnF2/SHMP with 1450 ppm F). Twenty-five subjects were randomized to a two-period, two-treatment, double blind crossover sequence using NaF/KNO3 (Sensodyne ProNamel dentifrice) and SnF2/SHMP (blend-a-med* EXPERT GUMS PROTECTION dentifrice). Each treatment was conducted with a standard manual toothbrush (Oral-B P35 Indicator). Digital plaque image analysis (DPIA) was used on three consecutive days to evaluate: (a) overnight plaque formation (A.M. pre-brushing); (b) following 40 seconds of brushing with the test product (A.M. post-brushing); and (c) mid-afternoon (P.M.). Images were analysed using an objective computer algorithm to calculate the total area of visible plaque. A four-day washout period was instituted for the crossover phase. All 25 subjects completed the study. The SnF2/SHMP positive control dentifrice provided statistically significantly lower levels of plaque area coverage versus the NaF/KNO3 test dentifrice at each timepoint. For the SnF2/SHMP dentifrice, plaque coverage was 23.0% lower (p< 0.0001) at A.M. pre-brushing, 17.3% (p= 0.0163) lower at A.M. post-brushing, and 22.6% (p= 0.0004) lower at the P.M. measure relative to the NaF/KNO3 dentifrice. The SnF2/SHMP dentifrice (blend-a-med EXPERT GUMS PROTECTION) inhibits plaque regrowth both overnight and during the day to a significantly greater degree than the NaF/KNO3 dentifrice (Sensodyne ProNamel). Dentists recommending an effective home use dentifrice for patients experiencing dentinal hypersensitivity and/or dental erosion may previously have needed to compromise on other key benefits, such as plaque control. blend-a-med EXPERT GUMS PROTECTION is a dentifrice when integrated into an oral hygiene routine can provide a proven treatment for hypersensitivity, dental erosion, and

  20. Translation of flecainide- and mexiletine-induced cardiac sodium channel inhibition and ventricular conduction slowing from nonclinical models to clinical.

    PubMed

    Heath, B M; Cui, Y; Worton, S; Lawton, B; Ward, G; Ballini, E; Doe, C P A; Ellis, C; Patel, B A; McMahon, N C

    2011-01-01

    Nonclinical in vivo models used for cardiovascular safety testing have not previously been studied for their sensitivity for detection of conduction slowing resulting from cardiac sodium channel block. The goal of this study was to examine the sensitivity of in vivo models to cardiac sodium channel block, and translation of the effect from in vitro to in vivo models using sodium channel inhibitors flecainide and mexiletine; flecainide, but not mexiletine is commonly associated with QRS complex prolongation in humans. Inhibition of cloned cardiac sodium channels (hNav1.5) was studied using the IonWorks platform. Conduction slowing was measured in vitro in the rabbit isolated ventricular wedge (RVW) and in vivo in the conscious telemetered rat and dog, and anaesthetised dog. Flecainide and mexiletine inhibited hNav1.5 channels with IC50 values of 10.7 and 67.2 μM respectively. In the RVW, QRS was increased by flecainide at 60 bpm, and at 120bpm, there was an increased effect of both drugs. In conscious rats, flecainide significantly increased QRS complex duration; mexiletine had no significant effect, but there was an increase at the highest dose in 4/6 animals. QRS complex was increased by flecainide and mexiletine in anaesthetised dogs but this was not statistically significant; in conscious dog, only flecainide produced a significant increase in QRS complex. When compared to clinical data, effects of flecainide and mexiletine in RVW and conscious dog compared well with effects in patients and healthy volunteers in terms of sensitivity. The anaesthetised dog was least sensitive for detection of changes in QRS. All assays showed some differentiation between the expected conduction slowing activity of flecainide and mexiletine. Based on these data, RVW and conscious dog were most predictive for effects of compounds on QRS complex and cardiac conduction. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. Lacosamide Inhibition of Nav1.7 Voltage-Gated Sodium Channels: Slow Binding to Fast-Inactivated States.

    PubMed

    Jo, Sooyeon; Bean, Bruce P

    2017-04-01

    Lacosamide is an antiseizure agent that targets voltage-dependent sodium channels. Previous experiments have suggested that lacosamide is unusual in binding selectively to the slow-inactivated state of sodium channels, in contrast to drugs like carbamazepine and phenytoin, which bind tightly to fast-inactivated states. Using heterologously expressed human Nav1.7 sodium channels, we examined the state-dependent effects of lacosamide. Lacosamide induced a reversible shift in the voltage dependence of fast inactivation studied with 100-millisecond prepulses, suggesting binding to fast-inactivated states. Using steady holding potentials, lacosamide block was very weak at -120 mV (3% inhibition by 100 µM lacosamide) but greatly enhanced at -80 mV (43% inhibition by 100 µM lacosamide), where there is partial fast inactivation but little or no slow inactivation. During long depolarizations, lacosamide slowly (over seconds) put channels into states that recovered availability slowly (hundreds of milliseconds) at -120 mV. This resembles enhancement of slow inactivation, but the effect was much more pronounced at -40 mV, where fast inactivation is complete, but slow inactivation is not, than at 0 mV, where slow inactivation is maximal, more consistent with slow binding to fast-inactivated states than selective binding to slow-inactivated states. Furthermore, inhibition by lacosamide was greatly reduced by pretreatment with 300 µM lidocaine or 300 µM carbamazepine, suggesting that lacosamide, lidocaine, and carbamazepine all bind to the same site. The results suggest that lacosamide binds to fast-inactivated states in a manner similar to other antiseizure agents but with slower kinetics of binding and unbinding.

  2. Inhibition of sodium-calcium exchange in cardiac sarcolemmal membrane vesicles. 1. Mechanism of inhibition by amiloride analogues

    SciTech Connect

    Slaughter, R.S.; Garcia, M.L.; Cragoe, E.J. Jr.; Reeves, J.P.; Kaczorowski, G.J.

    1988-04-05

    The mechanism by which terminal guanidino nitrogen substituted analogues of amiloride inhibit Na-Ca exchange in purified cardiac sarcolemmal membrane vesicles has been investigated. These inhibitors block both Na/sub i/-dependent Ca/sup 2 +/ uptake and Na/sub 0/-dependent Ca/sup 2 +/ efflux. Inhibition of Na-Ca exchange monitored in K/sup +/ is noncompetitive vs /sup 45/Ca/sup 2 +/ but competitive vs /sup 22/Na/sup +/. Substitution of sucrose for K/sup +/ results in mixed kinetics of inhibition vs /sup 45/Ca/sup 2 +/, suggesting a complex interaction between inhibitor and carrier under this condition. Amiloride derivatives also block two other modes of carrier action: Na-Na exchange is inhibited in a competitive fashion with Na/sup +/ and kinetics of Ca-Ca exchange inhibition are mixed vs Ca/sup 2 +/ in either sucrose or K/sup +/. However, Ca-Ca exchange inhibition can be alleviated by increasing K/sup +/ concentration. Dixon analyses of Na-Ca exchange block with mixtures of inhibitors suggest that these agents are interacting at more than one site. In addition, Hill plots of inhibition are biphasic with Hill coefficients of 1 and 2 at low and high inhibitor concentration, respectively. These results indicate that amiloride derivatives are mechanisms-based inhibitors that interact at two classes of substrate-binding sites on the carrier; at low concentration they bind preferentially to a site that is exclusive for Na/sup +/, while at higher concentration they also interact at a site that is common for Na/sup +/, Ca/sup 2 +/, and K/sup +/

  3. In vitro inhibition of hyaluronidase by sodium copper chlorophyllin complex and chlorophyllin analogs

    PubMed Central

    McCook, John P; Dorogi, Peter L; Vasily, David B; Cefalo, Dustin R

    2015-01-01

    Background Inhibitors of hyaluronidase are potent agents that maintain hyaluronic acid homeostasis and may serve as anti-aging, anti-inflammatory, and anti-microbial agents. Sodium copper chlorophyllin complex is being used therapeutically as a component in anti-aging cosmeceuticals, and has been shown to have anti-hyaluronidase activity. In this study we evaluated various commercial lots of sodium copper chlorophyllin complex to identify the primary small molecule constituents, and to test various sodium copper chlorophyllin complexes and their small molecule analog compounds for hyaluronidase inhibitory activity in vitro. Ascorbate analogs were tested in combination with copper chlorophyllin complexes for potential additive or synergistic activity. Materials and methods For hyaluronidase activity assays, dilutions of test materials were evaluated for hydrolytic activity of hyaluronidase by precipitation of non-digested hyaluronate by measuring related turbidity at 595 nm. High-performance liquid chromatography and mass spectroscopy was used to analyze and identify the primary small molecule constituents in various old and new commercial lots of sodium copper chlorophyllin complex. Results The most active small molecule component of sodium copper chlorophyllin complex was disodium copper isochlorin e4, followed by oxidized disodium copper isochlorin e4. Sodium copper chlorophyllin complex and copper isochlorin e4 disodium salt had hyaluronidase inhibitory activity down to 10 µg/mL. The oxidized form of copper isochlorin e4 disodium salt had substantial hyaluronidase inhibitory activity at 100 µg/mL but not at 10 µg/mL. Ascorbate derivatives did not enhance the hyaluronidase inhibitory activity of sodium copper chlorophyllin. Copper isochlorin e4 analogs were always the dominant components of the small molecule content of the commercial lots tested; oxidized copper isochlorin e4 was found in increased concentrations in older compared to newer lots tested

  4. Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: a population-based study.

    PubMed

    Fairhurst, Caroline; Watt, Ian; Martin, Fabiola; Bland, Martin; Brackenbury, William J

    2015-11-18

    Metastasis is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) regulate invasion and metastasis. Several VGSC-inhibiting drugs reduce metastasis in murine cancer models. We aimed to test the hypothesis that patients taking VGSC-inhibiting drugs who developed cancer live longer than those not taking these drugs. A cohort study was performed on primary care data from the QResearch database, including patients with breast, bowel or prostate cancer. Cox proportional hazards regression was used to compare the survival from cancer diagnosis of patients taking VGSC-inhibiting drugs with those not exposed to these drugs. Median time to death was 9.7 years in the exposed group and 18.4 years in the unexposed group, and exposure to these medications significantly increased mortality. Thus, exposure to VGSC-inhibiting drugs associates with reduced survival in breast, bowel and prostate cancer patients. This finding is not consistent with the preclinical data. Despite the strengths of this study including the large sample size, the study is limited by missing information on potentially important confounders such as cancer stage, co-morbidities and cause of death. Further research, which is able to account for these confounding issues, is needed to investigate the relationship between VGSC-inhibiting drugs and cancer survival.

  5. Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: a population-based study

    PubMed Central

    Fairhurst, Caroline; Watt, Ian; Martin, Fabiola; Bland, Martin; Brackenbury, William J.

    2015-01-01

    Metastasis is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) regulate invasion and metastasis. Several VGSC-inhibiting drugs reduce metastasis in murine cancer models. We aimed to test the hypothesis that patients taking VGSC-inhibiting drugs who developed cancer live longer than those not taking these drugs. A cohort study was performed on primary care data from the QResearch database, including patients with breast, bowel or prostate cancer. Cox proportional hazards regression was used to compare the survival from cancer diagnosis of patients taking VGSC-inhibiting drugs with those not exposed to these drugs. Median time to death was 9.7 years in the exposed group and 18.4 years in the unexposed group, and exposure to these medications significantly increased mortality. Thus, exposure to VGSC-inhibiting drugs associates with reduced survival in breast, bowel and prostate cancer patients. This finding is not consistent with the preclinical data. Despite the strengths of this study including the large sample size, the study is limited by missing information on potentially important confounders such as cancer stage, co-morbidities and cause of death. Further research, which is able to account for these confounding issues, is needed to investigate the relationship between VGSC-inhibiting drugs and cancer survival. PMID:26577038

  6. Treatment of antimony mine drainage: challenges and opportunities with special emphasis on mineral adsorption and sulfate reducing bacteria.

    PubMed

    Li, Yongchao; Hu, Xiaoxian; Ren, Bozhi

    2016-01-01

    The present article summarizes antimony mine distribution, antimony mine drainage generation and environmental impacts, and critically analyses the remediation approach with special emphasis on iron oxidizing bacteria and sulfate reducing bacteria. Most recent research focuses on readily available low-cost adsorbents, such as minerals, wastes, and biosorbents. It is found that iron oxides prepared by chemical methods present superior adsorption ability for Sb(III) and Sb(V). However, this process is more costly and iron oxide activity can be inhibited by plenty of sulfate in antimony mine drainage. In the presence of sulfate reducing bacteria, sulfate can be reduced to sulfide and form Sb(2)S(3) precipitates. However, dissolved oxygen and lack of nutrient source in antimony mine drainage inhibit sulfate reducing bacteria activity. Biogenetic iron oxide minerals from iron corrosion by iron-oxidizing bacteria may prove promising for antimony adsorption, while the micro-environment generated from iron corrosion by iron oxidizing bacteria may provide better growth conditions for symbiotic sulfate reducing bacteria. Finally, based on biogenetic iron oxide adsorption and sulfate reducing bacteria followed by precipitation, the paper suggests an alternative treatment for antimony mine drainage that deserves exploration.

  7. Antimony and silicon environments in antimony silicate glasses

    SciTech Connect

    Mee, M.; Davies, B.C.; Orman, R.G.; Thomas, M.F.; Holland, D.

    2010-09-15

    Antimony silicate glasses, of general formula xSb{sub 2}O{sub 3}.(1-x)SiO{sub 2} (0.1{<=}x{<=}0.78), have been prepared by melt-quenching and their structures studied using {sup 29}Si MAS NMR spectroscopy, {sup 121}Sb Moessbauer spectroscopy and Raman spectroscopy. Oxidation during melting gives rise to Sb{sup 5+} in concentrations, which increase linearly with x to give a value of {approx}10% when x=0.78. {sup 121}Sb Moessbauer spectra show Moessbauer shifts and quadrupole splittings consistent with Sb{sup 3+} in a [:SbO{sub 3}] trigonal pyramid, similar to that in crystalline Sb{sub 2}O{sub 3}. A broad band in the Raman spectrum at {approx}410 cm{sup -1} is due to the vibrations of such a unit. The dependence of the silicon Q{sup n} speciation on x can be interpreted by the formation of Sb-O-Sb links possibly to form rings of 4 [:SbO{sub 3}] units such as are found in valentinite. - Graphical abstract: Antimony silicate glasses have been shown to contain Sb{sup 3+} in [:SbO{sub 3}] trigonal pyramid units using {sup 121}Sb Moessbauer spectroscopy and Raman spectroscopy. {sup 29}Si magic-angle-spinning NMR has shown silicon Q{sup n} speciation which can be interpreted as formation of rings of 4 [:SbO{sub 3}] units such as are found in valentinite.

  8. Inhibition of boric acid and sodium borate on the biological activity of microorganisms in an aerobic biofilter.

    PubMed

    Güneş, Y

    2013-01-01

    The aim of this work was to study the inhibition effect of boric acid and sodium borate on the treatment of boron containing synthetic wastewater by a down flow aerobic fixed bed biofilm reactor at various chemical oxygen demand (COD)/boron ratios (0.47-20.54). The inhibitory effect of boron on activated sludge was evaluated on the basis of COD removal during the experimental period. The biofilter (effective volume = 2.5 L) was filled with a ring of plastic material inoculated with acclimated activated sludge. The synthetic wastewater composed of glucose, urea, KH2PO4, MgSO4, Fe2 SO4, ZnSO4 x 7H20, KCl, CaCl2, and di-sodium tetraborate decahydrate or boric acid (B = 100-2000 mg L(-1)). The biological treatment of boron containing wastewater resulted in a low treatment removal rate due to the reduced microbial activity as a result of toxic effects of high boron concentrations. The decrease in the COD removal rate by the presence of either boric acid or sodium borate was practically indistinguishable. It was observed from the experiments that about 90-95% of COD removal was possible at high COD/boron ratios.

  9. Salt-dependent inhibition of ENaC-mediated sodium reabsorption in the aldosterone-sensitive distal nephron by bradykinin

    PubMed Central

    Mamenko, Mykola; Zaika, Oleg; Doris, Peter A.; Pochynyuk, Oleh

    2012-01-01

    We have recently documented that Bradykinin (BK) directly inhibits activity of the Epithelial Na+ Channel (ENaC) via B2R-Gq/11-PLC pathway. In this study, we took advantage of mice genetically engineered to lack bradykinin receptors (B1R,B2R-/-) to probe a physiological role of BK cascade in regulation of ENaC in native tissue, aldosterone-sensitive distal nephron (ASDN). Under normal sodium intake (0.32%Na+), ENaC open probability (Po) was modestly elevated in B1R,B2R-/- mice compared to WT mice. This difference is augmented during elevated Na+ intake (2%Na+) and negated during Na+ restriction (<0.01%Na+). Saturation of systemic mineralocorticoid status with deoxycorticosterone acetate (DOCA) similarly increased ENaC activity in both mouse strains suggesting that the effect of BK on ENaC is independent of aldosterone. It is accepted that angiotensin converting enzyme (ACE) represents the major pathway of BK degradation. Systemic inhibition of ACE with captopril (30 mg/kgBW for 7 days) significantly decreases ENaC activity and Po in WT mice but this effect is diminished in B1R,B2R-/- mice. At the cellular level, acute captopril (100 μM) treatment sensitized BK signaling cascade and greatly potentiated the inhibitory effect of 100 nM BK on ENaC. We concluded that BK cascade has its own specific role in blunting ENaC activity particularly under conditions of elevated sodium intake. Augmentation of BK signaling in the ASDN inhibits ENaC-mediated Na+-reabsorption contributing to the natriuretic and antihypertensive effects of ACE inhibition. PMID:23033373

  10. The characteristics of inhibition of histamine release from human lung fragments by sodium cromoglycate, salbutamol and chlorpromazine

    PubMed Central

    Church, Martin K.; Young, Kevin D.

    1983-01-01

    1 Three drugs have been tested for activity against antigen-induced histamine release from passively sensitized human lung fragments after increasing periods of pre-incubation before challenge. 2 After 30 s pre-incubation, sodium cromoglycate inhibited histamine release in the concentration range 0.2-200 μM, producing a maximum inhibition of 33.0%. As the pretreatment period was extended, tolerance developed in a dose-related manner, resulting in a 48.3% and 82.8% loss of activity of the 200 μM dose after 60 min and 19 h pre-incubation, respectively. Tolerance was independent of extracellular calcium and was poorly reversible. Lung tissue desensitized to cromoglycate was cross-tolerant to the related drug, bufrolin, but not to salbutamol or chlorpromazine. 3 In acute studies, salbutamol (0.03-3.0 μM) produced dose-related inhibition of histamine release, with a maximum inhibition of 72.2%. The effect was blocked stereoselectively by 1 μM propranolol, suggesting that it occurred through an interaction with lung β-adrenoceptors. Increasing the pre-incubation time with salbutamol from 30 s to 19 h did not produce tolerance. Inhibition produced by incubation with salbutamol for 19 h was totally prevented when propranolol was added at the beginning of the pre-incubation period, indicating that it resulted from stimulation of β-receptors and not from a non-specific or toxic effect. However, studies of reversibility of effect through washing or late addition of propranolol did indicate some change in the nature of salbutamol inhibition with time. 4 Chlorpromazine was a weak inhibitor of immunological histamine release. A 100 μM concentration was ineffective after 30 s pre-incubation but its activity increased with time. Pre-incubation of lung fragments with this concentration for 1 h or longer, or with a 1 mM dose for a shorter period, provoked histamine release in the absence of antigen. Effects of chlorpromazine were not reversed by washing. 5 The different

  11. Inhibition of bacterial adhesion on PVC endotracheal tubes by RF-oxygen glow discharge, sodium hydroxide and silver nitrate treatments.

    PubMed

    Balazs, D J; Triandafillu, K; Wood, P; Chevolot, Y; van Delden, C; Harms, H; Hollenstein, C; Mathieu, H J

    2004-05-01

    Medical-grade poly(vinyl chloride) (PVC) was chemically modified to study how the incorporation of monovalent silver influences Pseudomonas aeruginosa adhesion and colonization. The modification investigated consisted of a radio frequency-oxygen (RF-O(2)) glow discharge pre-functionalization, followed by a two-step wet-treatment in sodium hydroxide and silver nitrate solutions. X-ray photoelectron spectroscopy (XPS) analysis and contact angle measurements were used to investigate the chemical nature and surface wettability of the films following each step of the modification. XPS analysis proved that the RF-O(2) plasma pre-functionalization of native PVC reproducibly increased the amount of functional groups representative of PVC additives, including ether/alcohol, esters and carboxyl groups. More specifically, we demonstrated that the O-C=O groups representative of the phthalic ester and zinc carboxylate additives identified for native PVC increased by two-fold following the RF-O(2) plasma pre-functionalization step. Although RF-O(2) pre-functionalization did not have an effect on the silver content of the NaOH/AgNO(3) treated substrates, such a modification was necessary for biomaterial products that did not have reproducible surfaces amongst production lots. XPS analysis also demonstrated that saponification with sodium hydroxide (NaOH) of esters, like those of the phthalic ester additives of PVC is a simple, irreversible method of hydrolysis, which produced sodium carboxylate and sodium phthalate salts. Exposure of native PVC to NaOH resulted in an increased surface hydrophilicity (from ca 90 degrees to ca 60 degrees ) due to dechlorination. XPS analysis following further incubation in silver nitrate demonstrated that silver ions can be trapped when the sodium of sodium carboxylate is replaced by silver after performing a second treatment with a monovalent silver-containing solution. The creation of silver salt on native PVC resulted in an ultra

  12. Sodium Butyrate Stimulates Expression of Fibroblast Growth Factor 21 in Liver by Inhibition of Histone Deacetylase 3

    PubMed Central

    Li, Huating; Gao, Zhanguo; Zhang, Jin; Ye, Xin; Xu, Aimin; Ye, Jianping; Jia, Weiping

    2012-01-01

    Fibroblast growth factor 21 (FGF21) stimulates fatty acid oxidation and ketone body production in animals. In this study, we investigated the role of FGF21 in the metabolic activity of sodium butyrate, a dietary histone deacetylase (HDAC) inhibitor. FGF21 expression was examined in serum and liver after injection of sodium butyrate into dietary obese C57BL/6J mice. The role of FGF21 was determined using antibody neutralization or knockout mice. FGF21 transcription was investigated in liver and HepG2 hepatocytes. Trichostatin A (TSA) was used in the control as an HDAC inhibitor. Butyrate was compared with bezafibrate and fenofibrate in the induction of FGF21 expression. Butyrate induced FGF21 in the serum, enhanced fatty acid oxidation in mice, and stimulated ketone body production in liver. The butyrate activity was significantly reduced by the FGF21 antibody or gene knockout. Butyrate induced FGF21 gene expression in liver and hepatocytes by inhibiting HDAC3, which suppresses peroxisome proliferator–activated receptor-α function. Butyrate enhanced bezafibrate activity in the induction of FGF21. TSA exhibited a similar set of activities to butyrate. FGF21 mediates the butyrate activity to increase fatty acid use and ketogenesis. Butyrate induces FGF21 transcription by inhibition of HDAC3. PMID:22338096

  13. Tolperisone-type drugs inhibit spinal reflexes via blockade of voltage-gated sodium and calcium channels.

    PubMed

    Kocsis, Pál; Farkas, Sándor; Fodor, László; Bielik, Norbert; Thán, Márta; Kolok, Sándor; Gere, Anikó; Csejtei, Mónika; Tarnawa, István

    2005-12-01

    The spinal reflex depressant mechanism of tolperisone and some of its structural analogs with central muscle relaxant action was investigated. Tolperisone (50-400 microM), eperisone, lanperisone, inaperisone, and silperisone (25-200 microM) dose dependently depressed the ventral root potential of isolated hemisected spinal cord of 6-day-old rats. The local anesthetic lidocaine (100-800 microM) produced qualitatively similar depression of spinal functions in the hemicord preparation, whereas its blocking effect on afferent nerve conduction was clearly stronger. In vivo, tolperisone and silperisone as well as lidocaine (10 mg/kg intravenously) depressed ventral root reflexes and excitability of motoneurons. However, in contrast with lidocaine, the muscle relaxant drugs seemed to have a more pronounced action on the synaptic responses than on the excitability of motoneurons. Whole-cell measurements in dorsal root ganglion cells revealed that tolperisone and silperisone depressed voltage-gated sodium channel conductance at concentrations that inhibited spinal reflexes. Results obtained with tolperisone and its analogs in the [3H]batrachotoxinin A 20-alpha-benzoate binding in cortical neurons and in a fluorimetric membrane potential assay in cerebellar neurons further supported the view that blockade of sodium channels may be a major component of the action of tolperisone-type centrally acting muscle relaxant drugs. Furthermore, tolperisone, eperisone, and especially silperisone had a marked effect on voltage-gated calcium channels, whereas calcium currents were hardly influenced by lidocaine. These data suggest that tolperisone-type muscle relaxants exert their spinal reflex inhibitory action predominantly via a presynaptic inhibition of the transmitter release from the primary afferent endings via a combined action on voltage-gated sodium and calcium channels.

  14. Antimony-doped graphene nanoplatelets

    PubMed Central

    Jeon, In-Yup; Choi, Min; Choi, Hyun-Jung; Jung, Sun-Min; Kim, Min-Jung; Seo, Jeong-Min; Bae, Seo-Yoon; Yoo, Seonyoung; Kim, Guntae; Jeong, Hu Young; Park, Noejung; Baek, Jong-Beom

    2015-01-01

    Heteroatom doping into the graphitic frameworks have been intensively studied for the development of metal-free electrocatalysts. However, the choice of heteroatoms is limited to non-metallic elements and heteroatom-doped graphitic materials do not satisfy commercial demands in terms of cost and stability. Here we realize doping semimetal antimony (Sb) at the edges of graphene nanoplatelets (GnPs) via a simple mechanochemical reaction between pristine graphite and solid Sb. The covalent bonding of the metalloid Sb with the graphitic carbon is visualized using atomic-resolution transmission electron microscopy. The Sb-doped GnPs display zero loss of electrocatalytic activity for oxygen reduction reaction even after 100,000 cycles. Density functional theory calculations indicate that the multiple oxidation states (Sb3+ and Sb5+) of Sb are responsible for the unusual electrochemical stability. Sb-doped GnPs may provide new insights and practical methods for designing stable carbon-based electrocatalysts. PMID:25997811

  15. Antimony-doped graphene nanoplatelets

    NASA Astrophysics Data System (ADS)

    Jeon, In-Yup; Choi, Min; Choi, Hyun-Jung; Jung, Sun-Min; Kim, Min-Jung; Seo, Jeong-Min; Bae, Seo-Yoon; Yoo, Seonyoung; Kim, Guntae; Jeong, Hu Young; Park, Noejung; Baek, Jong-Beom

    2015-05-01

    Heteroatom doping into the graphitic frameworks have been intensively studied for the development of metal-free electrocatalysts. However, the choice of heteroatoms is limited to non-metallic elements and heteroatom-doped graphitic materials do not satisfy commercial demands in terms of cost and stability. Here we realize doping semimetal antimony (Sb) at the edges of graphene nanoplatelets (GnPs) via a simple mechanochemical reaction between pristine graphite and solid Sb. The covalent bonding of the metalloid Sb with the graphitic carbon is visualized using atomic-resolution transmission electron microscopy. The Sb-doped GnPs display zero loss of electrocatalytic activity for oxygen reduction reaction even after 100,000 cycles. Density functional theory calculations indicate that the multiple oxidation states (Sb3+ and Sb5+) of Sb are responsible for the unusual electrochemical stability. Sb-doped GnPs may provide new insights and practical methods for designing stable carbon-based electrocatalysts.

  16. Speciation of antimony in polyethylene terephthalate bottles

    SciTech Connect

    Martin, R.R.; Ablett, J.; Shotyk, W.S.; Naftel, S.; Northrup, P.

    2009-12-18

    Antimony contamination has been reported in drinking water from polyethylene terephthalate (PET) bottles. Micro-X-ray fluorescence (XRF) analysis has been used to identify the distribution and chemical form of residual antimony used as a catalyst in the manufacture of PET bottles. The results are consistent with clusters of Sb(III) having dimensions of the order of tens of micrometers, clearly showing the ability of synchrotron radiation analyses to both map elemental distribution and determine oxidation state.

  17. Surface complexation of antimony on kaolinite.

    PubMed

    Rakshit, Sudipta; Sarkar, Dibyendu; Datta, Rupali

    2015-01-01

    Geochemical fate of antimony (Sb) - a similar oxyanion as arsenic (As) - in a variety of environment is largely unexplored. Kaolinite is an important, naturally occurring clay mineral in soils and aquifers and is known to control the fate of several contaminants via a multitude of geochemical processes, primarily adsorption. Here we report adsorption of antimony on kaolinite as a function of solution chemistry: initial antimony concentration, pH, ionic strength, and a competing anion. A surface complexation modeling (SCM) approach was undertaken to understand the potential mechanistic implications of sorption envelope data. In the SCM, a multicomponent additive approach, in which kaolinite is assumed to be a (1:1) mixture of quartz (≡SiOH) and gibbsite (≡AlOH), was tested. Results indicated that ionic strength has a minimal effect on antimony adsorption. For the lower initial antimony concentration (4.11 μM), the additive model with binuclear surface complexes on quartz and gibbsite showed a better fit at pH<6, but somewhat under predicted the experimental data above pH 6. At the higher initial antimony concentration (41.1 μM), the sorption envelope was of different shape than the lower load. The additive model, which considered binuclear surface complexes for quartz and gibbsite, resulted in over prediction of the adsorption data at pH>3.5. However, the additive model with binuclear surface complex on quartz and mononuclear surface complex on gibbsite showed an excellent fit of the data. Phosphate greatly influenced antimony adsorption on kaolinite at both low and high antimony loadings, indicating competition for available surface sites.

  18. δ ENaC: a novel divergent amiloride-inhibitable sodium channel

    PubMed Central

    Zhao, Run-Zhen; Chen, Zai-Xing; Shetty, Sreerama; Idell, Steven; Matalon, Sadis

    2012-01-01

    The fourth subunit of the epithelial sodium channel, termed delta subunit (δ ENaC), was cloned in human and monkey. Increasing evidence shows that this unique subunit and its splice variants exhibit biophysical and pharmacological properties that are divergent from those of α ENaC channels. The widespread distribution of epithelial sodium channels in both epithelial and nonepithelial tissues implies a range of physiological functions. The altered expression of SCNN1D is associated with numerous pathological conditions. Genetic studies link SCNN1D deficiency with rare genetic diseases with developmental and functional disorders in the brain, heart, and respiratory systems. Here, we review the progress of research on δ ENaC in genomics, biophysics, proteomics, physiology, pharmacology, and clinical medicine. PMID:22983350

  19. Inhibition of Sodium Ion Channel Function with Truncated Forms of Batrachotoxin.

    PubMed

    Toma, Tatsuya; Logan, Matthew M; Menard, Frederic; Devlin, A Sloan; Du Bois, J

    2016-10-19

    A novel family of small molecule inhibitors of voltage-gated sodium channels (NaVs) based on the structure of batrachotoxin (BTX), a well-known channel agonist, is described. Protein mutagenesis and electrophysiology experiments reveal the binding site as the inner pore region of the channel, analogous to BTX, alkaloid toxins, and local anesthetics. Homology modeling of the eukaryotic channel based on recent crystallographic analyses of bacterial NaVs suggests a mechanism of action for ion conduction block.

  20. Benefits of sodium hexametaphosphate-containing chewing gum for extrinsic stain inhibition.

    PubMed

    Walters, Patricia A; Biesbrock, Aaron R; Bartizek, Robert D

    2004-01-01

    This study was designed to examine the ability of sodium hexametaphosphate delivered from a chewing gum to prevent extrinsic tooth stain formation. This study was a negative-controlled, randomized, two-period crossover design, with a 10-day washout period between treatments. The two treatments were a chewing gum containing 5.6% sodium hexametaphosphate and a negative control chewing gum. Eleven subjects who met study criteria were enrolled, and 10 completed the study over a two-week period. Each treatment period lasted approximately 48 hours and was separated by a washout period. After a dental prophylaxis, a digital image of the anterior teeth was taken to assess baseline stain. The three-day stain induction phase consisted of the patient using a 10 ml 0.2% chlorhexidine rinse for 60 seconds, followed by chewing two pellets/sticks of their assigned gum for five minutes and rinsing with 10 ml of cold tea solution for 60 seconds. No oral hygiene was permitted other than use of the test products. During both treatment periods, each subject followed the same regimen eight times, once per hour, throughout the day. On Days 2 and 3, the adjusted mean L* measurement was statistically significantly greater for the sodium hexametaphosphate gum than for the control gum. Moreover, nine of the 10 subjects had whiter teeth while on the experimental gum treatment at both Day 2 and Day 3. The results of this study support that sodium hexametaphosphate delivered from a chewing gum prevents dental stain formation and leads to a patient-desired whitening benefit.

  1. Resveratrol inhibits sodium/iodide symporter gene expression and function in rat thyroid cells.

    PubMed

    Giuliani, Cesidio; Bucci, Ines; Di Santo, Serena; Rossi, Cosmo; Grassadonia, Antonino; Mariotti, Marianna; Piantelli, Mauro; Monaco, Fabrizio; Napolitano, Giorgio

    2014-01-01

    Resveratrol is a polyphenol found in grapes and berries that has antioxidant, antiproliferative and anti-inflammatory properties. For these reasons, it is available as a dietary supplement, and it is under investigation in several clinical trials. Few data are available regarding the effects of resveratrol on thyroid function. A previous study showed that resveratrol transiently increases iodide influx in FRTL-5 rat thyroid cells. Indeed, this increase arises after short treatment times (6-12 h), and no further effects are seen after 24 h. The aim of the present study was to investigate the effects of resveratrol on iodide uptake and sodium/iodide symporter expression in thyroid cells after longer times of treatment. For this purpose, the effects of resveratrol were evaluated both in vitro and in vivo using the rat thyroid FRTL-5 cell line and Sprague-Dawley rats, respectively. In FRTL-5 cells, resveratrol decreased the sodium/iodide symporter RNA and protein expression as a function of time. Furthermore, resveratrol decreased cellular iodide uptake after 48 h of treatment. The inhibitory effect of resveratrol on iodide uptake was confirmed in vivo in Sprague-Dawley rats. This study demonstrates that with longer-term treatment, resveratrol is an inhibitor of sodium/iodide symporter gene expression and function in the thyroid. These data suggest that resveratrol can act as a thyroid disruptor, which indicates the need for caution as a supplement and in therapeutic use.

  2. Resveratrol Inhibits Sodium/Iodide Symporter Gene Expression and Function in Rat Thyroid Cells

    PubMed Central

    Giuliani, Cesidio; Bucci, Ines; Di Santo, Serena; Rossi, Cosmo; Grassadonia, Antonino; Mariotti, Marianna; Piantelli, Mauro; Monaco, Fabrizio; Napolitano, Giorgio

    2014-01-01

    Resveratrol is a polyphenol found in grapes and berries that has antioxidant, antiproliferative and anti-inflammatory properties. For these reasons, it is available as a dietary supplement, and it is under investigation in several clinical trials. Few data are available regarding the effects of resveratrol on thyroid function. A previous study showed that resveratrol transiently increases iodide influx in FRTL-5 rat thyroid cells. Indeed, this increase arises after short treatment times (6–12 h), and no further effects are seen after 24 h. The aim of the present study was to investigate the effects of resveratrol on iodide uptake and sodium/iodide symporter expression in thyroid cells after longer times of treatment. For this purpose, the effects of resveratrol were evaluated both in vitro and in vivo using the rat thyroid FRTL-5 cell line and Sprague-Dawley rats, respectively. In FRTL-5 cells, resveratrol decreased the sodium/iodide symporter RNA and protein expression as a function of time. Furthermore, resveratrol decreased cellular iodide uptake after 48 h of treatment. The inhibitory effect of resveratrol on iodide uptake was confirmed in vivo in Sprague-Dawley rats. This study demonstrates that with longer-term treatment, resveratrol is an inhibitor of sodium/iodide symporter gene expression and function in the thyroid. These data suggest that resveratrol can act as a thyroid disruptor, which indicates the need for caution as a supplement and in therapeutic use. PMID:25251397

  3. Sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the CPRD primary care database

    PubMed Central

    Fairhurst, Caroline; Martin, Fabiola; Watt, Ian; Doran, Tim; Bland, Martin

    2016-01-01

    Introduction Voltage-gated sodium channel (VGSC)-inhibiting drugs are commonly used to treat epilepsy and cardiac arrhythmia. VGSCs are also widely expressed in various cancers, including those of the breast, bowel and prostate. A number of VGSC-inhibiting drugs have been shown to inhibit cancer cell proliferation, invasion, tumour growth and metastasis in preclinical models, suggesting that VGSCs may be novel molecular targets for cancer treatment. Surprisingly, we previously found that prior exposure to VGSC-inhibiting drugs may be associated with reduced overall survival in patients with cancer, but we were unable to control for the cause of death or indication for prescription. The purpose of the present study is to interrogate a different database to further investigate the relationship between VGSC-inhibiting drugs and cancer-specific survival. Methods and analysis A cohort study using primary care data from the Clinical Practice Research Datalink database will include patients with diagnosis of breast, bowel and prostate cancer (13 000). The primary outcome will be cancer-specific survival from the date of cancer diagnosis. Cox proportional hazards regression will be used to compare survival of patients taking VGSC-inhibiting drugs (including antiepileptic drugs and class I antiarrhythmic agents) with patients with cancer not taking these drugs, adjusting for cancer type, age and sex. Drug exposure will be treated as a time-varying covariate to account for potential immortal time bias. Various sensitivity and secondary analyses will be performed. Ethics and dissemination The project has been reviewed and approved by the University of York Ethical Review Process. Results will be presented at an international conference and published in open access peer-reviewed journals according to the STROBE and RECORD guidelines. PMID:27601493

  4. Histamine release by exocytosis from rat mast cells on reduction of extracellular sodium: a secretory response inhibited by calcium, strontium, barium or magnesium.

    PubMed Central

    Cochrane, D E; Douglas, W W

    1976-01-01

    1. Histamine release from peritoneal mast cells of the rat was stimulated when the cells were exposed for 10 min to sodium-deficient media where all NaCl had been replaced by KC1, RbC1, glucose, sucrose, mannitol, or Tris, provided calcium was less than about 0-5 mM. 2. Light and electron microscopy showed the response to be exocytosis. 3. The chelating agents, EDTA and EGTA, abolished the response to sodium lack and their inhibitory effects were reversed by re-incubating cells with calcium but not magnesium. 4. The response was inhibited by dinitrophenol combined with glucose-deprivation. 5. The response was inversely related to the concentrations of sodium and calcium below 137-5 and 0-5 mM respectively. 6. The related alkaline earth metals, barium, strontium, and magnesium, resembled calcium in inhibiting the response to sodium lack. 7. No secretory response was seen when the cells were exposed for 10 min to calcium-free medium in which lithium replaced sodium. Exposure to this medium for 60 min, however, elicited secretion. 8. It is concluded that when extracellular calcium is low, a reduction in extracellular sodium induces a conventional exocytotic secretory response dependent on energy and cellular calcium. It is suggested that sodium lack may mobilize calcium from a cellular site possibly the inner aspect of the plasma membrane. Images A B C D E F G H PMID:59804

  5. Liposomal amphotericin B versus pentavalent antimony salts for visceral Leishmania in children.

    PubMed

    Apa, Hurşit; Devrim, İlker; Bayram, Nuri; Deveci, Reyhan; Demir-Özek, Gülcihan; Cartı, Özgür Umaç

    2013-01-01

    The aim of this study was to investigate the efficacy of a 21-day schedule of liposomal amphotericin B compared to pentavalent antimony salts in the treatment of patients during a first episode of visceral leishmaniasis. In this study, 17 cases of visceral leishmaniasis admitted to Behçet Uz Children's Hospital between January 2005 and April 2012 were reviewed retrospectively. The study group was composed of 11 males (64.7%) and 6 females (35.3%). One group included 11 patients who were treated with pentavalent antimony salts, sodium stibogluconate or meglumine antimoniate, intramuscularly for 28 days. The second group was treated with amphotericin B intravenously at a dosage of 3 mg/kg on days 1-5, 10 and 21 (a cumulative dose of 21 mg/kg/day). While pentavalent antimony salts were found to increase biochemical and hematological findings, liposomal amphotericin B was responsible for rapid recovery in fever and shorter hospital stay. As a result, our study shows the advantages of both medications independent of their costs.

  6. Antimony sulphide thin film as an absorber in chemically deposited solar cells

    NASA Astrophysics Data System (ADS)

    Messina, Sarah; Nair, M. T. S.; Nair, P. K.

    2008-05-01

    Antimony sulfide thin films (thickness, 500 nm) were deposited on chemically deposited CdS thin films (100 nm) obtained on 3 mm glass substrates coated with a transparent conductive coating of SnO2:F (TEC-15 with 15 Ω sheet resistance). Two different chemical formulations were used for depositing antimony sulfide films. These contained (i) antimony trichloride dissolved in acetone and sodium thiosulfate, and (ii) potassium antimony tartrate, triethanolamine, ammonia, thioacetamide and small concentrations of silicotungstic acid. The films were heated at 250 °C in nitrogen. The cell structure was completed by depositing a 200 nm p-type PbS thin film. Graphite paint applied on the PbS thin film and a subsequent layer of silver paint served as the p-side contact. The cell structure: SnO2:F/CdS/Sb2S3 (i or ii)/PbS showed open circuit voltage (Voc) of 640 mV and short circuit current density (Jsc) above 1 mA cm-2 under 1 kW m-2 tungsten-halogen radiation. Four cells, each of 1.7 cm2 area, were series-connected to give Voc of 1.6 V and a short circuit current of 4.1 mA under sunlight (1060 W m-2).

  7. Randomized controlled trial to study plaque inhibition in calcium sodium phosphosilicate dentifrices.

    PubMed

    Claydon, Nicholas C A; Hall, Claire; Hughes, Alison J; Shaw, David; Seong, Joon; Davies, Maria; West, Nicola X

    2016-03-01

    To evaluate the effect of three calcium sodium phosphosilicate (CSPS)/sodium monofluorophosphate containing dentifrices, compared to positive and negative controls on plaque re-growth in a non-brushing model, after 4 days of twice daily use, as determined by plaque area and Turesky plaque index (TPI). This was an exploratory, single-centre, examiner-blind, randomised, controlled, five treatment period, crossover, plaque re-growth study, with supervised use of study products. Twenty-three healthy adult volunteers were randomized to receive experimental 5% CSPS dentifrice; two marketed 5% CSPS dentifrices; active comparator mouthrinse and negative control dentifrice. At the start of each treatment period, zero plaque was established by dental prophylaxis and study products were dispensed as either dentifrice slurries or mouthrinse, twice daily for the next 4 days. No other forms of oral hygiene were permitted. After 96h, supra-gingival plaque was determined by plaque area (direct entry, planimetric method) and TPI. Changes from zero plaque were analysed. For both measures, plaque re-growth at 96h was significantly lower following treatment with active comparator mouthrinse and significantly higher following treatment with the experimental 5% CSPS dentifrice, compared to all other treatments. There were no statistically significant differences between the three other treatments, except between the marketed 5% CSPS dentifrices, for overall plaque area. The comparator mouthwash was significantly more effective at preventing plaque accumulation than the dentifrice slurries. The three marketed dentifrices contained sodium lauryl sulphate and were more effective at reducing plaque re-growth than the experimental dentifrice formulated with a tegobetaine/adinol surfactant system. The CSPS containing dentifrices tested in this study showed no significant chemical-therapeutic anti-plaque benefits compared to a negative control dentifrice. However, sodium lauryl sulphate

  8. Downregulation of mitogen-activated protein kinase 1 of Leishmania donovani field isolates is associated with antimony resistance.

    PubMed

    Ashutosh; Garg, Mansi; Sundar, Shyam; Duncan, Robert; Nakhasi, Hira L; Goyal, Neena

    2012-01-01

    Emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (VL) on the Indian subcontinent. The mechanisms operating in laboratory-generated strains are somewhat known, but the determinants of clinical antimony resistance are not well understood. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding mitogen-activated protein kinase 1 (MAPK1) for the kinetoplast protozoan Leishmania donovani (LdMAPK1) that was consistently downregulated in antimony-resistant field isolates. The expression level of the gene was validated by real-time PCR. Furthermore, decreased expression of LdMAPK1 was also confirmed at the protein level in resistant isolates. Primary structure analysis of LdMAPK1 revealed the presence of all of the characteristic features of MAPK1. When expressed in Escherichia coli, the recombinant enzyme showed kinase activity with myelin basic protein as the substrate and was inhibited by staurosporine. Interestingly, overexpression of this gene in a drug-sensitive laboratory strain and a resistant field isolate resulted in increased the sensitivity of the transfectants to potassium antimony tartrate, suggesting that it has a role in antimony resistance. Our results demonstrate that downregulation of LdMAPK1 may be in part correlated with antimony drug resistance in Indian VL isolates.

  9. Downregulation of Mitogen-Activated Protein Kinase 1 of Leishmania donovani Field Isolates Is Associated with Antimony Resistance

    PubMed Central

    Ashutosh; Garg, Mansi; Sundar, Shyam; Duncan, Robert; Nakhasi, Hira L.

    2012-01-01

    Emergence of resistance to pentavalent antimonials has become a severe obstacle in the treatment of visceral leishmaniasis (VL) on the Indian subcontinent. The mechanisms operating in laboratory-generated strains are somewhat known, but the determinants of clinical antimony resistance are not well understood. By utilizing a DNA microarray expression profiling approach, we identified a gene encoding mitogen-activated protein kinase 1 (MAPK1) for the kinetoplast protozoan Leishmania donovani (LdMAPK1) that was consistently downregulated in antimony-resistant field isolates. The expression level of the gene was validated by real-time PCR. Furthermore, decreased expression of LdMAPK1 was also confirmed at the protein level in resistant isolates. Primary structure analysis of LdMAPK1 revealed the presence of all of the characteristic features of MAPK1. When expressed in Escherichia coli, the recombinant enzyme showed kinase activity with myelin basic protein as the substrate and was inhibited by staurosporine. Interestingly, overexpression of this gene in a drug-sensitive laboratory strain and a resistant field isolate resulted in increased the sensitivity of the transfectants to potassium antimony tartrate, suggesting that it has a role in antimony resistance. Our results demonstrate that downregulation of LdMAPK1 may be in part correlated with antimony drug resistance in Indian VL isolates. PMID:22064540

  10. LL202 protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting MAPK/AP-1 signaling

    PubMed Central

    Zhao, Yue; Hu, Yang; Li, Zhiyu; Guo, Qinglong; Zhao, Kai; Lu, Na

    2016-01-01

    LL202, a newly-synthesized flavonoid derivative, has been reported to inhibit inflammatory-induced angiogenesis. However, the exact role of LL202 in inflammation along with its mechanism has not been explored. In this study, we investigated the anti-inflammatory effect of LL202 on intestinal inflammation by establishing dextran sulfate sodium (DSS)-induced experimental colitis. LL202 attenuated DSS-induced body weight loss, colon length shortening and colonic pathological damage. The inflammatory cells infiltration, myeloperoxidase (MPO) and inducible nitric oxide synthase (iNOS) activities were decreased by LL202 in a dose-dependent manner. LL202 reduced the production of pro-inflammatory cytokines in serum and colon of DSS-induced mice as well. Mechanically, LL202 could decrease the expression and nuclear translation of AP-1 to protect against DSS-induced colitis. In lipopolysaccharide (LPS)-induced THP-1 cells, LL202 markedly decreased the secretion, mRNA level and protein expression of IL-1β, IL-6 and TNF-α via inhibiting ERK/JNK/p38 MAPK pathways and the nuclear translocation of AP-1. Furthermore, these findings were confirmed in LPS-induced bone marrow derived macrophages (BMDM). In conclusion, our study demonstrated that LL202 could exert its anti-inflammatory effect via inhibiting MAPK/AP-1 signaling, which suggested that LL202 might be a potential effective drug for the treatment of inflammatory bowel diseases. PMID:27590510

  11. Selective inhibition of the late sodium current has no adverse effect on electrophysiological or contractile function of the normal heart.

    PubMed

    Fernandes, Sarah; Hoyer, Kirsten; Liu, Gongxin; Wang, Wei-Qun; Dhalla, Arvinder K; Belardinelli, Luiz; Rajamani, Sridharan

    2014-06-01

    Inhibition of cardiac late Na(+) current (I(Na,L)) decreases sodium-dependent calcium overload in diseased hearts. Because INa,L is small in the absence of disease, its inhibition is not expected to significantly alter function of the normal heart. To test this hypothesis, we determined the effects of GS-458967 (GS967), a novel selective inhibitor of I(Na,L) (IC(50) = 0.13 μM), on cardiac function and hemodynamics. The bradycardic agent ivabradine and the Na(+) channel blocker flecainide were used for comparison. A single per os administration of GS967 (5 mg/kg) had no effect on blood pressure or heart rate (HR) in unanesthetized rats. In anesthetized rats, GS967 (0.6 ± 0.1 μM plasma concentration) had no significant effect on HR, PR or QRS electrocardiogram intervals, or contraction. Flecainide (8 mg/kg) slowed HR by 23% ± 3% (P < 0.001), prolonged the PR and QRS intervals by 42% ± 8% and 64% ± 12% (P < 0.001), and had a significant negative inotropic effect. Ivabradine (3 mg/kg) slowed HR by 36% ± 6% (P < 0.001). In rat and rabbit isolated perfused hearts, GS967 (0.1-3 μM) had no significant effects on HR, QRS interval, or contractile function. The results show that selective inhibition of cardiac I(Na,L) is not associated with chronotropic, dromotropic, inotropic, or hemodynamic changes.

  12. Inhibition of antibacterial activity of himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus, by fatty acid sodium salts.

    PubMed Central

    Mamber, S W; Brookshire, K W; Dean, B J; Firestone, R A; Leet, J E; Matson, J A; Forenza, S

    1994-01-01

    Himastatin, a cyclohexadepsipeptide antibiotic, had in vivo antitumor activity against localized P388 leukemia and B16 melanoma but had no distal site antitumor activity. An in vitro Bacillus subtilis well-agar diffusion assay was employed to test the hypothesis that himastatin was enzymatically inactivated. The activity of himastatin against B. subtilis was inhibited when himastatin was mixed with mouse liver S9 fraction and microsomes. However, subsequent investigations demonstrated that the markedly decreased antibacterial activity was not enzymatic in nature but was related to the presence of certain fatty acid salts. Saturated fatty acid sodium salts with a carbon chain number of 8 or more reduced the antimicrobial activity of himastatin 50 to 100 times. If antibiotics such as ampicillin, bacitracin, chloramphenicol, and tunicamycin were used in place of himastatin, no meaningful reduction in antibacterial activity occurred. However, the antibacterial activity of the membrane-active peptide antibiotic polymyxin B, but not that of polymyxin E (colistin), was reduced in a manner similar to that of himastatin. Importantly, the activity of himastatin against HCT-116 colon adenocarcinoma cells in soft agar was markedly reduced in the presence of sodium palmitate as the reference fatty acid salt. The data indicate that himastatin may be trapped in micelles in vitro. It may be speculated that the lack of distal site antitumor activity resulted from similar complex formation between himastatin and lipids in vivo. The results also suggest that the cancer cytotoxic and antimicrobial effects of himastatin may result from interactions with the cell membrane. PMID:7872760

  13. Inhibition of cultured bovine aortic endothelial cell proliferation by sodium spirulan, a new sulfated polysaccharide isolated from Spirulina platensis.

    PubMed

    Kaji, Toshiyuki; Fujiwara, Yasuyuki; Hamada, Chieko; Yamamoto, Chika; Shimada, Satomi; Lee, Jung-Bum; Hayashi, Toshimitsu

    2002-06-01

    Sodium spirulan (Na-SP) is a sulfated polysaccharide isolated from the blue-green alga Spirulina platensis, which consists of two types of disaccharide repeating units, O-hexuronosyl-rhamnose (aldobiuronic acid) and O-rhamnosyl-3-O-methylrhamnose (acofriose) with sulfate groups, other minor saccharides and sodium ion. Vascular endothelial cells are present on the inner surface of blood vessels in a monolayer and have anticoagulant properties. To address the question whether Na-SP influences the maintenance of endothelial cell monolayers, we investigated the proliferation of cultured bovine aortic endothelial cells treated with Na-SP. It was found that Na-SP has an inhibitory activity on endothelial cell proliferation accompanied with suppression of whole protein synthesis but without non-specific cell damage. The inhibitory activity of Na-SP was the strongest when compared to that of heparan sulfate, heparin, dextran sulfate, dermatan sulfate, chondroitin sulfate A/C and hyaluronan. Furthermore, it was shown that the inhibitory activity of Na-SP disappeared by either desulfation or depolymerization. The present data suggest that Na-SP is a unique sulfated polysaccharide that strongly inhibits vascular endothelial cell proliferation, and the inhibitory activity requires polymerization of sulfated O-rhamnosyl-acofriose repeating units.

  14. CP-MLR/PLS directed QSAR study on apical sodium-codependent bile acid transporter inhibition activity of benzothiepines.

    PubMed

    Sharma, Brij Kishore; Singh, Prithvi; Pilania, Pradeep; Sarbhai, Kirti; Prabhakar, Yenamandra S

    2011-02-01

    The apical sodium-codependent bile acid transporter (ASBT) inhibition activity of benzothiepine derivatives have been analyzed based on topological and molecular features. Analysis of the structural features in conjunction with the biological endpoints in Combinatorial Protocol in Multiple Linear Regression (CP-MLR) led to the identification of 21 descriptors for modeling the activity. The study clearly suggested that the role of Randic shape index (path/walk ratio 3) and topological charges of 2-, 5-, and 6-orders to optimize the ASBT inhibitory activity of titled compounds. The influence of atomic van der Waals volumes, masses, Sanderson electronegativities, and polarizabilities are indicated via different lags of Moran and Geary autocorrelations. Presence of tertiary aromatic amine functionality in molecular structure has also shown its relevance in rationalizing the biological actions of benzothiepines. The PLS analysis has confirmed the dominance of information content of CP-MLR identified descriptors for modeling the activity when compared to those of the leftover ones.

  15. Conotoxins That Could Provide Analgesia through Voltage Gated Sodium Channel Inhibition

    PubMed Central

    Munasinghe, Nehan R.; Christie, MacDonald J.

    2015-01-01

    Chronic pain creates a large socio-economic burden around the world. It is physically and mentally debilitating, and many sufferers are unresponsive to current therapeutics. Many drugs that provide pain relief have adverse side effects and addiction liabilities. Therefore, a great need has risen for alternative treatment strategies. One rich source of potential analgesic compounds that has emerged over the past few decades are conotoxins. These toxins are extremely diverse and display selective activity at ion channels. Voltage gated sodium (NaV) channels are one such group of ion channels that play a significant role in multiple pain pathways. This review will explore the literature around conotoxins that bind NaV channels and determine their analgesic potential. PMID:26690478

  16. Selective inhibition of persistent sodium current by F 15845 prevents ischaemia-induced arrhythmias

    PubMed Central

    Pignier, C; Rougier, J-S; Vié, B; Culié, C; Verscheure, Y; Vacher, B; Abriel, H; Le Grand, B

    2010-01-01

    BACKGROUND AND PURPOSE Myocardial ischaemia is associated with perturbations of electrophysiological profile of cardiac myocytes. The persistent sodium current (INap) is one of the major contributors to ischaemic arrhythmias and appears as an attractive therapeutic target. We investigated the effects of F 15845, a new anti-anginal drug on INap and in integrative models of INap-induced arrhythmias. EXPERIMENTAL APPROACH Sodium current was investigated using patch clamp technique on wild-type and ΔKPQ-mutated hNav1.5 channels transfected in HEK293 cells. Effects of F 15845 on action potentials (APs) were studied by the glass microelectrode technique and its anti-arrhythmic activities were investigated in ischaemia- and aconitine-induced arrhythmias in the rat. KEY RESULTS We demonstrated that F 15845 is a potent blocker of INap acting from the extracellular side of the channel. Blockade of INap was voltage dependent and characterized by an almost pure tonic block. F 15845 shortened AP from rabbit Purkinje fibres, confirming its lack of pro-arrhythmic activity, and prevented AP lengthening induced by the INap activator veratridine. F 15845 did not affect APs from rabbit atria and guinea pig papillary muscle where INap is not functional, confirming its inability to affect other cardiac ionic currents. F 15845 was effective at preventing fatal ventricular fibrillation and ventricular tachycardia during coronary ligation without modifying heart rate and blood pressure, and dose dependently increased the dose threshold of aconitine required to induce ventricular arrhythmias. CONCLUSIONS AND IMPLICATIONS F 15845, a novel anti-anginal drug targeting INap, demonstrates new anti-arrhythmic properties which may be of therapeutic benefit against ischaemia-induced arrhythmias PMID:20718741

  17. Antimony: a modular model definition language.

    PubMed

    Smith, Lucian P; Bergmann, Frank T; Chandran, Deepak; Sauro, Herbert M

    2009-09-15

    Model exchange in systems and synthetic biology has been standardized for computers with the Systems Biology Markup Language (SBML) and CellML, but specialized software is needed for the generation of models in these formats. Text-based model definition languages allow researchers to create models simply, and then export them to a common exchange format. Modular languages allow researchers to create and combine complex models more easily. We saw a use for a modular text-based language, together with a translation library to allow other programs to read the models as well. The Antimony language provides a way for a researcher to use simple text statements to create, import, and combine biological models, allowing complex models to be built from simpler models, and provides a special syntax for the creation of modular genetic networks. The libAntimony library allows other software packages to import these models and convert them either to SBML or their own internal format. The Antimony language specification and the libAntimony library are available under a BSD license from http://antimony.sourceforge.net/.

  18. 40 CFR 721.1930 - Butanoic acid, antimony (3=) salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Butanoic acid, antimony (3=) salt. 721... Substances § 721.1930 Butanoic acid, antimony (3=) salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as butanoic acid, antimony (3=) salt (PMN...

  19. 40 CFR 721.1930 - Butanoic acid, antimony (3=) salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Butanoic acid, antimony (3=) salt. 721... Substances § 721.1930 Butanoic acid, antimony (3=) salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as butanoic acid, antimony (3=) salt (PMN...

  20. 40 CFR 721.1930 - Butanoic acid, antimony (3=) salt.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Butanoic acid, antimony (3=) salt. 721... Substances § 721.1930 Butanoic acid, antimony (3=) salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as butanoic acid, antimony (3=) salt (PMN...

  1. 40 CFR 721.1930 - Butanoic acid, antimony (3=) salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Butanoic acid, antimony (3=) salt. 721... Substances § 721.1930 Butanoic acid, antimony (3=) salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as butanoic acid, antimony (3=) salt (PMN...

  2. 40 CFR 721.1930 - Butanoic acid, antimony (3=) salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Butanoic acid, antimony (3=) salt. 721... Substances § 721.1930 Butanoic acid, antimony (3=) salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as butanoic acid, antimony (3=) salt (PMN...

  3. 40 CFR 721.5547 - Antimony double oxide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Antimony double oxide. 721.5547... Substances § 721.5547 Antimony double oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as antimony double oxide (PMNs P-95-677 and P...

  4. 40 CFR 721.5547 - Antimony double oxide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Antimony double oxide. 721.5547... Substances § 721.5547 Antimony double oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as antimony double oxide (PMNs P-95-677 and P...

  5. 40 CFR 721.5547 - Antimony double oxide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Antimony double oxide. 721.5547... Substances § 721.5547 Antimony double oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as antimony double oxide (PMNs P-95-677 and P...

  6. 40 CFR 721.5547 - Antimony double oxide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Antimony double oxide. 721.5547... Substances § 721.5547 Antimony double oxide. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as antimony double oxide (PMNs P-95-677 and P...

  7. 40 CFR 721.10712 - Antimony tris(dialkyldithiocarbamate) (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Antimony tris(dialkyldithiocarbamate... Specific Chemical Substances § 721.10712 Antimony tris(dialkyldithiocarbamate) (generic). (a) Chemical... as antimony tris(dialkyldithiocarbamate) (PMN P-13-217) is subject to reporting under this section...

  8. 40 CFR 721.10713 - Antimony tris(dialkyldithiocarbamate) (generic).

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Antimony tris(dialkyldithiocarbamate... Specific Chemical Substances § 721.10713 Antimony tris(dialkyldithiocarbamate) (generic). (a) Chemical... as antimony tris(dialkyldithiocarbamate) (PMN P-13-259) is subject to reporting under this section...

  9. Inhibition of carbachol-evoked oscillatory currents by the NO donor sodium nitroprusside in guinea-pig ileal myocytes.

    PubMed

    Chung, Seung-Soo; Ahn, Duck-Sun; Lee, Hong-Ghi; Lee, Young-Ho; Nam, Taick-Sang

    2005-07-01

    The effect of sodium nitroprusside (SNP) on carbachol (CCh)-evoked inward cationic current (Icat) oscillations in guinea-pig ileal longitudinal myocytes was investigated using the whole-cell patch-clamp technique and permeabilized longitudinal muscle strips. SNP (10 microm) completely inhibited I(cat) oscillations evoked by 1 microm CCh. 1H-(1,2,4) Oxadiazole [4,3-a] quinoxaline-1-one (ODQ; 1 microm) almost completely prevented the inhibitory effect of SNP on Icat oscillations. 8-Bromo-guanosine 3',5'-cyclic monophosphate (8-Br-cGMP; 30 microm) in the pipette solution completely abolished Icat oscillations. However, a pipette solution containing Rp-8-Br-cGMP (30 microm) almost completely abolished the inhibitory effect of SNP on Icat oscillations. When the intracellular calcium concentration ([Ca2+]i) was held at a resting level using BAPTA (10 mm) and Ca2+ (4.6 microm) in the pipette solution, CCh (1 microm) evoked only the sustained component of Icat without any oscillations and SNP did not affect the current. A high concentration of inositol 1,4,5-trisphosphate (IP3; 30 microm) in the patch pipette solutions significantly reduced the inhibitory effect of SNP (10 microm) on Icat oscillations. SNP significantly inhibited the Ca2+ release evoked by either CCh or IP3 but not by caffeine in permeabilized preparations of longitudinal muscle strips. These results suggest that the inhibitory effects of SNP on Icat oscillations are mediated, in part, by functional modulation of the IP3 receptor, and not by the inhibition of cationic channels themselves or by muscarinic receptors in the plasma membrane. This inhibition seems to be mediated by an increased cGMP concentration in a protein kinase G-dependent manner.

  10. Microcolumn sorption of antimony(III) chelate for antimony speciation studies

    NASA Astrophysics Data System (ADS)

    Garboś, Sławomir; Rzepecka, Monika; Bulska, Ewa; Hulanicki, Adam

    1999-05-01

    Selective sorption of the Sb(III) chelate with ammonium pyrrolidine dithiocarbamate (APDC) on a microcolumn packed with C 16-bonded silica gel phase was used for the determination of Sb(III) and of total inorganic antimony after reducing Sb(V) to Sb(III) by L-cysteine. A flow injection system composed of a microcolumn connected to the tip of the autosampler was used for preconcentration. The sorbed antimony was directly eluted with ethanol into the graphite furnace and determined by AAS. The detection limit for antimony was significantly lowered to 0.007 μg l -1 in comparison to 1.7 μg l -1 for direct injection GFAAS. This procedure was applied for speciation determinations of inorganic antimony in tap water, snow and urine samples. For the investigation of long-term stability of antimony species a flow injection hydride generation atomic absorption spectrometry with quartz tube atomization (FI HG QT AAS) and GFAAS were used for selective determination of Sb(III) in the presence of Sb(V) and total content of antimony, respectively. Investigations on the stability of antimony in several natural samples spiked with Sb(III) and Sb(V) indicated instability of Sb(III) in tap water and satisfactory stability of inorganic Sb species in the presence of urine matrix.

  11. Potent inhibition of anoxic depolarization by the sodium channel blocker dibucaine

    PubMed Central

    Douglas, Heather A.; Callaway, Jennifer K.; Sword, Jeremy; Kirov, Sergei A.

    2011-01-01

    Recurring waves of peri-infarct depolarizations (PIDs) propagate across gray matter in the hours and days following stroke, expanding the primary site of injury. Ischemic depolarization (termed anoxic depolarization or AD in live brain slices) is PID-like but immediately arises in the more metabolically compromised ischemic core. This causes dramatic neuronal and astrocyte swelling and dendritic beading with spine loss within minutes, resulting in acute cell death. AD is evoked in rodent neocortical slices by suppressing the Na+/K+-ATPase pump with either oxygen/glucose deprivation (OGD) or exposure to ouabain. The process driving AD and PIDs remains poorly understood. Here we show that dibucaine is a potent drug inhibiting AD because of its high binding affinity to the Na+ channel. Field recording reveals that, when superfused with ouabain (5 min), neocortical slices pretreated with 1 μM dibucaine for 45 min display either no AD or delayed AD onset compared with untreated controls. If ouabain exposure is extended to 10 min, 1 μM dibucaine is still able to delay AD onset by ∼60%. Likewise, it delays OGD-evoked AD onset by ∼54% but does not depress action potentials (APs) or evoked orthodromic field potentials. Increasing dibucaine to 10 μM inhibits AP firing, gradually putting the slice into a stasis that inhibits AD onset but also renders the slice functionally quiescent. Two-photon microscopy reveals that 10 μM dibucaine pretreatment prevents or helps reverse ouabain-induced structural neuronal damage. Although the therapeutic range of dibucaine is quite narrow, dibucaine-like drugs could prove therapeutically useful in inhibiting PIDs and their resultant neuronal damage. PMID:21273307

  12. Histopathological and functional effects of antimony on the renal cortex of growing albino rat

    PubMed Central

    Rashedy, Ahmed H; Solimany, Adnan A; Ismail, Ayman K; Wahdan, Mohamed H; Saban, Khalid A

    2013-01-01

    Contamination of the environment with antimony compounds may affect human health through the persistent exposure to small doses over a long period. Sixty growing male albino rats, weighing 43-57 grams, utilized in this study. The animals were divided into 3 groups; each of 20 rats: animals of group I served as control, animals of group II received 6 mg/kg body weight antimony trisulfide daily for 8 weeks with drinking water, and those of group III received the same dose by the same route for 12 weeks. The Malpighian renal corpuscles showed distortion, destruction and congestion of glomerular tuft, vacuoles in the glomeruli, peritubular haemorrhage, obliteration of Bowman’s space, and thickening with irregularity of Bowman’s membrane. The proximal convoluted tubules demonstrated patchy loss of their brush border, thickening of the basement membrane with loss of its basal infoldings, disarrangement of the mitochondria, pleomorphic vacuoles in the cytoplasm, apical destruction of the cells, apical migration of the nuclei, and absence of microvilli. On the other hand, peri-tubular hemorrhage, apical vacuolation, small atrophic nuclei, swelling of mitochondria, obliteration of the lumina, destruction of cells, and presence of tissue debris in the lumina, were observed in the distal convoluted tubules. The present work demonstrated the hazardous effect of antimony on the renal function as evidenced by the significant increase of the level of blood urea, serum creatinine, and serum sodium and potassium. In conclusion, this study proposed that continuous oral administration of antimony for 8 and 12 weeks has hazardous toxic effect on the structure and function of the kidney in growing albino rat. Based on the results of the present study, it is recommended to avoid the use of any drinking water contaminated with antimony compounds and forbidden its use in infants and children foods. PMID:23923065

  13. Histopathological and functional effects of antimony on the renal cortex of growing albino rat.

    PubMed

    Rashedy, Ahmed H; Solimany, Adnan A; Ismail, Ayman K; Wahdan, Mohamed H; Saban, Khalid A

    2013-01-01

    Contamination of the environment with antimony compounds may affect human health through the persistent exposure to small doses over a long period. Sixty growing male albino rats, weighing 43-57 grams, utilized in this study. The animals were divided into 3 groups; each of 20 rats: animals of group I served as control, animals of group II received 6 mg/kg body weight antimony trisulfide daily for 8 weeks with drinking water, and those of group III received the same dose by the same route for 12 weeks. The Malpighian renal corpuscles showed distortion, destruction and congestion of glomerular tuft, vacuoles in the glomeruli, peritubular haemorrhage, obliteration of Bowman's space, and thickening with irregularity of Bowman's membrane. The proximal convoluted tubules demonstrated patchy loss of their brush border, thickening of the basement membrane with loss of its basal infoldings, disarrangement of the mitochondria, pleomorphic vacuoles in the cytoplasm, apical destruction of the cells, apical migration of the nuclei, and absence of microvilli. On the other hand, peri-tubular hemorrhage, apical vacuolation, small atrophic nuclei, swelling of mitochondria, obliteration of the lumina, destruction of cells, and presence of tissue debris in the lumina, were observed in the distal convoluted tubules. The present work demonstrated the hazardous effect of antimony on the renal function as evidenced by the significant increase of the level of blood urea, serum creatinine, and serum sodium and potassium. In conclusion, this study proposed that continuous oral administration of antimony for 8 and 12 weeks has hazardous toxic effect on the structure and function of the kidney in growing albino rat. Based on the results of the present study, it is recommended to avoid the use of any drinking water contaminated with antimony compounds and forbidden its use in infants and children foods.

  14. Lactic acid bacteria inhibit proinflammatory cytokine expression and bacterial glycosaminoglycan degradation activity in dextran sulfate sodium-induced colitic mice.

    PubMed

    Lee, Hye-Sung; Han, Song-Yi; Bae, Eun-Ah; Huh, Chul-Sung; Ahn, Young-Tae; Lee, Jung-Hee; Kim, Dong-Hyun

    2008-04-01

    To evaluate the effect of lactic acid bacteria (LAB) in inflammatory bowel diseases (IBD), inhibitory effect of several LAB isolated from intestinal microflora and commercial probiotics against NO production of lipopolysaccharide (LPS)-stimulated RAW264.7 cells was measured and anti-inflammatory effect of NO production-inhibitory LAB, Lactobacillus plantarum HY115 and L. brevis HY7401, in dextran sulfate sodium (DSS)-induced experimental colitic mice was investigated. The oral administration of the LAB to mice inhibited colon shortening and myeloperoxidase productivity in DSS-induced colitic mice. These LABs repressed the mRNA expressions of IL-1beta, TNF-alpha and IFN-gamma, as well as the protein expressions of IL-1beta and IL-6 proteins in the colon. The activation of the transcription factor, NF-kB, induced by DSS, was also inhibited by LAB. The administration of LAB reduced the degradation activities of chondroitin sulfate and hyaluronic acid of intestinal bacteria, induced by DSS, of which could induce the cytotoxic metabolites against intestinal cells. These findings suggest that NO-inhibitory LAB against LPS-stimulated RAW264.7 cells may improve colitis by the regulation of the inflammatory cytokine expression via the activation of transcription factor NF-kB as well as GAGs-degrading intestinal microflora.

  15. Sodium orthovanadate inhibits growth of human hepatocellular carcinoma cells in vitro and in an orthotopic model in vivo.

    PubMed

    Wu, Yaohua; Ma, Yong; Xu, Zhilin; Wang, Dawei; Zhao, Baolei; Pan, Huayang; Wang, Jizhou; Xu, Dongsheng; Zhao, Xiaoyang; Pan, Shangha; Liu, Lianxin; Dai, Wenjie; Jiang, Hongchi

    2014-08-28

    The transition metal vanadium is widely distributed in the environment and exhibits various biological and physiological effects in the human body. As a well known vanadium compound, sodium orthovanadate (SOV) has shown promising antineoplastic activity in several human cancers. However, the effects of SOV on liver cancer are still unknown. In this study, for the first time, we showed that SOV could effectively suppress proliferation, induce G2/M cell cycle arrest and apoptosis, and diminish the mitochondrial membrane potential (MMP) of HCC cells in vitro. In addition, our in vitro results were recapitulated in vivo, showing that SOV exhibited a dose-dependent inhibition of growth of human HCC in an orthotopic model, evidenced by the reduction in tumor size, proliferation index and microvessel density, and increase in cell apoptosis. Most important, we found that SOV could inhibit autophagy in HCC cells in vitro and in vivo, which plays a prodeath role. Thus, our findings suggest that SOV could effectively suppress the growth of human HCC through the regulations of proliferation, cell cycle, apoptosis and autophagy, and thus may act as a potential therapeutic agent in HCC treatment.

  16. Development of a screening approach to detect thyroid disrupting chemicals that inhibit the human sodium iodide symporter (NIS).

    PubMed

    Hallinger, Daniel R; Murr, Ashley S; Buckalew, Angela R; Simmons, Steven O; Stoker, Tammy E; Laws, Susan C

    2017-04-01

    The U.S. EPA's Endocrine Disruptor Screening Program aims to use high-throughput assays and computational toxicology models to screen and prioritize chemicals that may disrupt the thyroid signaling pathway. Thyroid hormone biosynthesis requires active iodide uptake mediated by the sodium/iodide symporter (NIS). Monovalent anions, such as the environmental contaminant perchlorate, are competitive inhibitors of NIS, yet limited information exists for more structurally diverse chemicals. A novel cell line expressing human NIS, hNIS-HEK293T-EPA, was used in a radioactive iodide uptake (RAIU) assay to identify inhibitors of NIS-mediated iodide uptake. The RAIU assay was optimized and performance evaluated with 12 reference chemicals comprising known NIS inhibitors and inactive compounds. An additional 39 chemicals including environmental contaminants were evaluated, with 28 inhibiting RAIU over 20% of that observed for solvent controls. Cell viability assays were performed to assess any confounding effects of cytotoxicity. RAIU and cytotoxic responses were used to calculate selectivity scores to group chemicals based on their potential to affect NIS. RAIU IC50 values were also determined for chemicals that displayed concentration-dependent inhibition of RAIU (≥50%) without cytotoxicity. Strong assay performance and highly reproducible results support the utilization of this approach to screen large chemical libraries for inhibitors of NIS-mediated iodide uptake.

  17. Neutrophils influx and proinflammatory cytokines inhibition by sodium salicylate, unlike aspirin, in Candida albicans-induced peritonitis model.

    PubMed

    Pereira, Priscilla Aparecida Tártari; Bini, Daniel; Bovo, Fernanda; Faccioli, Lucia Helena; Monteiro, Marta Chagas

    2016-07-01

    Sodium salicylate (NaS) and aspirin (ASA) are known to have a variety of effects on microorganisms, such as fungus (C. albicans and C. neoformans), moreover, it have effects in leukocyte adhesion and migration in vitro. In this report, we investigated the effect of ASA and NaS in neutrophil migration and cytokine production in C. albicans-induced peritonitis murine model. For this, mice were treated intraperitoneally (i.p) or orally (po) with NaS or ASA; after they were stimulated i.p. with C. albicans, the cellular migration was evaluated 24 h after stimulation. NaS, in mice treated i.p., unlike ASA, was able to inhibit the neutrophil migration and proinflammatory cytokine production induced by C. albicans, such as TNF-α, IL-1, IFN-γ, IL-12, and IL-10, but did not alter the IL-4 levels in these animals. However, the po treatment with same the dose of NaS or ASA did not affect the influx of this cell for inflammatory site. These results suggest that the NaS inhibits cellular migration and proinflammatory cytokine by different anti-inflammatory mechanism compared to ASA.

  18. Synergistic effects between sodium tripolyphosphate and zinc sulfate in corrosion inhibition for copper in neutral tap water

    SciTech Connect

    Feng, Y.; Siow, K.S.; Teo, W.K.; Tan, K.L.; Hsieh, A.K.

    1997-07-01

    The corrosion inhibition behavior of sodium tripolyphosphate (Na{sub 5}P{sub 3}O{sub 10}, or TPP) and zinc sulfate and the synergistic effects between them were studied for copper in neutral simulated tap water using electrochemical methods, x-ray photoelectron spectroscopy, and scanning electron microscopy. Zn{sup 2+} alone showed few inhibiting effects on copper corrosion. The film formed in the presence of Zn{sup 2+} was porous and composed mainly of cuprous oxide, which was similar in morphology and composition to films formed in the absence of the inhibitor. In the presence of TPP, a smooth and compact film, believed to be of Cu(II)-TPP compounds, formed on the copper surface. More protective films were formed in solutions containing TPP and Zn{sup 2+} as a blend. High zinc content (15% to 19%) was detected by XPS. Synergistic effects of TPP and Zn{sup 2+} were believed to result from formation of Zn(II)-TPP compounds that incorporated in the films, with Cu(II)-TPP in the upper layer and Cu{sub 2}O in the inner layer. The zinc compounds increased the anodic diffusion resistance of copper ions in the films and enhanced polarization of the cathodic reduction of dissolved oxygen.

  19. Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation.

    PubMed

    Zhan, Janis Ya-Xian; Wang, Xiu-Fen; Liu, Yu-Hong; Zhang, Zhen-Biao; Wang, Lan; Chen, Jian-Nan; Huang, Song; Zeng, Hui-Fang; Lai, Xiao-Ping

    2016-01-01

    Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent.

  20. Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus

    PubMed Central

    Abdul-Ghani, Muhammad A.; Norton, Luke

    2015-01-01

    Hyperglycemia is the primary factor responsible for the microvascular, and to a lesser extent macrovascular, complications of diabetes. Despite this well-established relationship, approximately half of all type 2 diabetic patients in the US have a hemoglobin A1c (HbA1c) ≥7.0%. This is associated in part with the side effects, i.e., weight gain and hypoglycemia, of currently available antidiabetic agents and in part with the failure to utilize medications that reverse the basic pathophysiological defects present in patients with type 2 diabetes. The kidney has been shown to play a central role in the development of hyperglycemia by excessive production of glucose throughout the sleeping hours and enhanced reabsorption of filtered glucose by the renal tubules secondary to an increase in the threshold at which glucose spills into the urine. Recently, a new class of antidiabetic agents, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, has been developed and approved for the treatment of patients with type 2 diabetes. In this review, we examine their mechanism of action, efficacy, safety, and place in the therapeutic armamentarium. Since the SGLT2 inhibitors have a unique mode of action that differs from all other oral and injectable antidiabetic agents, they can be used at all stages of the disease and in combination with all other antidiabetic medications. PMID:26354881

  1. Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus.

    PubMed

    Raskin, Philip

    2013-07-01

    Results from randomized controlled trials have demonstrated that the risk of microvascular complications can be reduced by intensive glycaemic control in patients with type 2 diabetes mellitus (T2DM). However, only about half of patients with diagnosed diabetes achieve recommended glycaemic goals. New therapies with complementary mechanisms of action that are independent of insulin secretion or action may provide additional therapeutic options to enable patients to achieve glycaemic control. The kidney plays an important role in glucose homeostasis, primarily by the reabsorption of filtered glucose. The sodium-glucose cotransporter 2 (SGLT2), located in the proximal convoluted tubule, is responsible for the majority of glucose reabsorption by the kidney. SGLT2 inhibitors offer a novel approach to treat T2DM and reduce hyperglycaemia by increasing urinary excretion of glucose. Dapagliflozin, an SGLT2 inhibitor recently approved in Europe for the treatment of T2DM, improves glycaemic control in patients with T2DM when used as monotherapy or when added to other diabetes medications, such as metformin, sulfonylureas, pioglitazone, and insulin. As a class, SGLT2 inhibitors are well tolerated and have a low propensity to cause hypoglycaemia. An increase in signs, symptoms, and other events suggestive of genital and, in some studies, urinary tract infections has been reported with SGLT2 inhibitors. Results from ongoing and future clinical trials will help define the role for this new class of investigational compounds, with its unique mechanism of action, as a treatment option for reducing hyperglycaemia in patients with T2DM.

  2. Inhibition effects on fermentation of hardwood extracted hemicelluloses by acetic acid and sodium.

    PubMed

    Walton, Sara; van Heiningen, Adriaan; van Walsum, Peter

    2010-03-01

    Extraction of hemicellulose from hardwood chips prior to pulping is a possible method for producing ethanol and acetic acid in an integrated forest bio-refinery, adding value to wood components normally relegated to boiler fuel. Hemicellulose was extracted from hardwood chips using green liquor, a pulping liquor intermediate consisting of aqueous NaOH, Na(2)CO(3), and Na(2)S, at 160 degrees C, held for 110 min in a 20 L rocking digester. The extracted liquor contained 3.7% solids and had a pH of 5.6. The organic content of the extracts was mainly xylo-oligosaccharides and acetic acid. Because it was dilute, the hemicellulose extract was concentrated by evaporation in a thin film evaporator. Concentrates from the evaporator reached levels of up to 10% solids. Inhibitors such as acetic acid and sodium were also concentrated by this method, presenting a challenge for the fermentation organisms. Fermentation experiments were conducted with Escherichia coli K011. The un-concentrated extract supported approximately 70% conversion of the initial sugars in 14 h. An extract evaporated down to 6% solids was also fermentable while a 10% solids extract was not initially fermentable. Strain conditioning was later found to enable fermentation at this level of concentration. Alternative processing schemes or inhibitor removal prior to fermentation are necessary to produce ethanol economically.

  3. Andrographolide Sodium Bisulfate Prevents UV-Induced Skin Photoaging through Inhibiting Oxidative Stress and Inflammation

    PubMed Central

    Zhan, Janis Ya-Xian; Wang, Xiu-Fen; Liu, Yu-Hong; Zhang, Zhen-Biao; Wang, Lan; Chen, Jian-Nan; Huang, Song; Zeng, Hui-Fang; Lai, Xiao-Ping

    2016-01-01

    Andrographolide sodium bisulfate (ASB), a water-soluble form made from andrographolide through sulfonating reaction, is an antioxidant and anti-inflammatory drug; however, the antiphotoaging effect of ASB has still not been revealed. Oxidative stress and inflammation are known to be responsible for ultraviolet (UV) irradiation induced skin damage and consequently premature aging. In this study, we aimed at examining the effect of ASB on UV-induced skin photoaging of mice by physiological and histological analysis of skin and examination of skin antioxidant enzymes and immunity analyses. Results showed that topical administration of ASB suppressed the UV-induced skin thickness, elasticity, wrinkles, and water content, while ASB, especially at dose of 3.6 mg/mouse, increased the skin collagen content by about 53.17%, decreased the epidermal thickness by about 41.38%, and prevented the UV-induced disruption of collagen fibers and elastic fibers. Furthermore, ASB decreased MDA level by about 40.21% and upregulated the activities of SOD and CAT and downregulated the production of IL-1β, IL-6, IL-10, and TNF-α in UV-irradiated mice. Our study confirmed the protective effect of ASB against UV-induced photoaging and initially indicated that this effect can be attributed to its antioxidant and anti-inflammatory activities in vivo, suggesting that ASB may be a potential antiphotoaging agent. PMID:26903706

  4. Flecainide reduces Ca2+ spark and wave frequency via inhibition of the sarcolemmal sodium current

    PubMed Central

    Sikkel, Markus B.; Collins, Thomas P.; Rowlands, Christina; Shah, Mit; O'Gara, Peter; Williams, Alan J.; Harding, Sian E.; Lyon, Alexander R.; MacLeod, Kenneth T.

    2013-01-01

    Aims Ca2+ waves are thought to be important in the aetiology of ventricular tachyarrhythmias. There have been conflicting results regarding whether flecainide reduces Ca2+ waves in isolated cardiomyocytes. We sought to confirm whether flecainide inhibits waves in the intact cardiomyocyte and to elucidate the mechanism. Methods and results We imaged spontaneous sarcoplasmic reticulum (SR) Ca2+ release events in healthy adult rat cardiomyocytes. Variation in stimulation frequency was used to produce Ca2+ sparks or waves. Spark frequency, wave frequency, and wave velocity were reduced by flecainide in the absence of a reduction of SR Ca2+ content. Inhibition of INa via alternative pharmacological agents (tetrodotoxin, propafenone, or lidocaine) produced similar changes. To assess the contribution of INa to spark and wave production, voltage clamping was used to activate contraction from holding potentials of −80 or −40 mV. This confirmed that reducing Na+ influx during myocyte stimulation is sufficient to reduce waves and that flecainide only causes Ca2+ wave reduction when INa is active. It was found that Na+/Ca2+-exchanger (NCX)-mediated Ca2+ efflux was significantly enhanced by flecainide and that the effects of flecainide on wave frequency could be reversed by reducing [Na+]o, suggesting an important downstream role for NCX function. Conclusion Flecainide reduces spark and wave frequency in the intact rat cardiomyocyte at therapeutically relevant concentrations but the mechanism involves INa reduction rather than direct ryanodine receptor (RyR2) inhibition. Reduced INa results in increased Ca2+ efflux via NCX across the sarcolemma, reducing Ca2+ concentration in the vicinity of the RyR2. PMID:23334259

  5. Inhibition of human Na(v)1.5 sodium channels by strychnine and its analogs.

    PubMed

    Yuan, Chunhua; Sun, Lirong; Zhang, Meng; Li, Shuji; Wang, Xuemin; Gao, Tianming; Zhu, Xinhong

    2011-08-15

    Strychnine and brucine from the seeds of the plant Strychnos nux vomica have been shown to have interesting pharmacological effects on several neurotransmitter receptors. In this study, we have characterized the pharmacological properties of strychnine and its analogs on human Na(v)1.5 channels to assess their potential therapeutic advantage in certain arrhythmias. Among the eight alkaloids, only strychnine and icajine exhibited inhibition potency on the Na(v)1.5 channel with the half-maximum inhibition (IC(50)) values of 83.1μM and 104.6μM, respectively. Structure-function analysis indicated that the increased bulky methoxy groups on the phenyl ring or the negatively charged oxygen atom may account for this lack of inhibition on the Na(v)1.5 channel. Strychnine and icajine may bind to the channel by cation-π interactions. The substitution with a large side chain on the phenyl ring or the increased molecular volume may alter the optimized position for the compound close to the binding sites of the channel. Strychnine and icajine bind to the Na(v)1.5 channel with a new mechanism that is different from TTX and local anesthetics. They bind to the outer vestibule of the channel pore with fast association and dissociation rates at resting state. Strychnine and icajine had little effect on steady-state fast inactivation but markedly shifted the slow inactivation of Na(v)1.5 currents toward more hyperpolarized potentials. The property of icajine influencing slow-inactivated state of Na(v)1.5 channel would be potential therapeutic advantages in certain arrhythmias. Copyright © 2011 Elsevier Inc. All rights reserved.

  6. Role of the Local Anesthetic Receptor in the State-Dependent Inhibition of Voltage-Gated Sodium Channels by the Insecticide Metaflumizone

    PubMed Central

    von Stein, Richard T.

    2012-01-01

    Sodium channel inhibitor (SCI) insecticides selectively target voltage-gated sodium (Nav) channels in the slow-inactivated state by binding at or near the local anesthetic receptor within the sodium channel pore. Metaflumizone is a new insecticide for the treatment of fleas on domesticated pets and has recently been reported to block insect sodium channels in the slow-inactivated state, thereby implying that it is also a member of the SCI class. Using the two-electrode voltage-clamp technique, we examined metaflumizone inhibition of rat Nav1.4 sodium channels expressed in Xenopus laevis oocytes. Metaflumizone selectively inhibited Nav1.4 channels at potentials that promoted slow inactivation and shifted the voltage dependence of slow inactivation in the direction of hyperpolarization. Metaflumizone perfusion at a hyperpolarized holding potential also shifted the conductance-voltage curve for activation in the direction of depolarization and antagonized use-dependent lidocaine inhibition of fast-inactivated sodium channels, actions not previously observed with other SCI insecticides. We expressed mutated Nav1.4/F1579A and Nav1.4/Y1586A channels to investigate whether metaflumizone shares the domain IV segment S6 (DIV-S6) binding determinants identified for other SCI insecticides. Consistent with previous investigations of SCI insecticides on rat Nav1.4 channels, the F1579A mutation reduced sensitivity to block by metaflumizone, whereas the Y1586A mutation paradoxically increased the sensitivity to metaflumizone. We conclude that metaflumizone selectively inhibits slow-inactivated Nav1.4 channels and shares DIV-S6 binding determinants with other SCI insecticides and therapeutic drugs. However, our results suggest that metaflumizone interacts with resting and fast-inactivated channels in a manner that is distinct from other compounds in this insecticide class. PMID:22127519

  7. Speciation of antimony(III) and antimony(V) by electrothermal atomic absorption spectrometry after ultrasound-assisted emulsification of solidified floating organic drop microextraction.

    PubMed

    Wen, Shengping; Zhu, Xiashi

    2013-10-15

    A simple, sensitive and efficient method of ultrasound-assisted emulsification of solidified floating organic drop microextraction (USE-SFODME) coupled to electrothermal atomic absorption spectrometry for the speciation of antimony at different oxidation state Sb(III)/Sb(V) in environmental samples was established. In this method, the hydrophobic complex of Sb(III) with sodium diethyldithiocarbamate (DDTC) is extracted by 1-undecanol at pH 9.0, while Sb(V) remains in aqueous phase. Sb(V) content can be calculated by subtracting Sb(III) from the total antimony after reducing Sb(V) to Sb(III) by l-cysteine. Various factors affecting USE-SFODME including pH, extraction solvent and its volume, concentration of DDTC, sonication time, and extraction temperature were investigated. Under the optimized conditions, the calibration curve was linear in the range from 0.05 to 10.0 ng mL(-1), with the limit of detection (3σ) 9.89 ng L(-1) for Sb(III). The relative standard deviation for Sb(III) was 4.5% (n=9, c=1.0 ng mL(-1)). This method was validated against the certified reference materials (GSB 07-1376-2001, GBW07441), and applied to the speciation of antimony in environmental samples (soil and water samples) with satisfactory results.

  8. Drug hypersensitivity syndrome induced by meglumine antimoniate.

    PubMed

    Jeddi, Fakhri; Caumes, Eric; Thellier, Marc; Jauréguiberry, Stéphane; Mazier, Dominique; Buffet, Pierre A

    2009-06-01

    We report a case of drug hypersensitivity syndrome (drug reaction with eosinophilia and systemic symptoms [DRESS]) induced by parenteral meglumine antimoniate (Glucantime) in a 40-year-old man who traveled to Bolivia and was treated for mucocutaneous leishmaniasis. Two weeks after starting therapy, the patient had fever, joint pain, a cutaneous eruption, and hypereosinophilia (1,358 cells/mm(3)). These symptoms resolved after drug withdrawal but reappeared upon reintroduction of the drug. Pentavalent antimonials should be definitively withdrawn in patients with hypereosinophilia > 1,000 cells/mm(3) accompanied by systemic manifestations consistent with DRESS.

  9. Trifluoperazine-Induced Suicidal Erythrocyte Death and S-Nitrosylation Inhibition, Reversed by the Nitric Oxide Donor Sodium Nitroprusside.

    PubMed

    Ghashghaeinia, Mehrdad; Wesseling, Mauro Carlos; Ramos, Elena; Petkova-Kirova, Polina; Waibel, Sabrina; Lang, Elisabeth; Bissinger, Rosi; Alzoubi, Kossai; Edelmann, Baerbel; Hosseinzadeh, Zohreh; Dreischer, Peter; Shahvaroughi-Farahani, Azam; Mrowietz, Ulrich; Köberle, Martin; Kaestner, Lars; Bernhardt, Ingolf; Martínez-Ruiz, Antonio; Wieder, Thomas; Lang, Florian

    2017-08-09

    The high potency antipsychotic drug trifluoperazine (10-[3-(4-methyl-1-piperazinyl)-propyl]-2-(trifluoromethyl)-(10)H-phenothiazine dihydrochloride; TFP) may either counteract or promote suicidal cell death or apoptosis. Similar to apoptosis, erythrocytes may enter eryptosis, characterized by phosphatidylserine exposure at the cell surface and cell shrinkage. Eryptosis can be stimulated by an increase in cytoplasmic Ca2+ concentration ([Ca2+]i) and inhibited by nitric oxide (NO). We explored whether TFP treatment of erythrocytes induces phosphatidylserine exposure, cell shrinkage, and calcium influx, whether it impairs S-nitrosylation and whether these effects are inhibited by NO. Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, and protein nitrosylation from fluorescence switch of the Bodipy-TMR/Sypro Ruby signal. Exposure of human erythrocytes to TFP significantly enhanced the percentage of annexin-V-binding cells, raised [Ca2+]i, and decreased S-nitrosylation. The effect of TFP on annexin-V-binding was not affected by removal of extracellular Ca2+ alone, but was significantly inhibited by pre-treatment with sodium nitroprusside (SNP), an effect significantly augmented by additional removal of extracellular Ca2+. A 3 hours treatment with 0.1 µM Ca2+ ionophore ionomycin triggered annexin-V-binding and cell shrinkage, effects fully reversed by removal of extracellular Ca2+. TFP induces eryptosis and decreases protein S-nitrosylation, effects blunted by nitroprusside. The effect of nitroprusside is attenuated in the presence of extracellular Ca2+. © 2017 The Author(s). Published by S. Karger AG, Basel.

  10. Intestinal Sodium Glucose Cotransporter 1 Inhibition Enhances Glucagon-Like Peptide-1 Secretion in Normal and Diabetic Rodents.

    PubMed

    Oguma, Takahiro; Nakayama, Keiko; Kuriyama, Chiaki; Matsushita, Yasuaki; Yoshida, Kumiko; Hikida, Kumiko; Obokata, Naoyuki; Tsuda-Tsukimoto, Minoru; Saito, Akira; Arakawa, Kenji; Ueta, Kiichiro; Shiotani, Masaharu

    2015-09-01

    The sodium glucose cotransporter (SGLT) 1 plays a major role in glucose absorption and incretin hormone release in the gastrointestinal tract; however, the impact of SGLT1 inhibition on plasma glucagon-like peptide-1 (GLP-1) levels in vivo is controversial. We analyzed the effects of SGLT1 inhibitors on GLP-1 secretion in normoglycemic and hyperglycemic rodents using phloridzin, CGMI [3-(4-cyclopropylphenylmethyl)-1-(β-d-glucopyranosyl)-4-methylindole], and canagliflozin. These compounds are SGLT2 inhibitors with moderate SGLT1 inhibitory activity, and their IC50 values against rat SGLT1 and mouse SGLT1 were 609 and 760 nM for phloridzin, 39.4 and 41.5 nM for CGMI, and 555 and 613 nM for canagliflozin, respectively. Oral administration of these inhibitors markedly enhanced and prolonged the glucose-induced plasma active GLP-1 (aGLP-1) increase in combination treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, in normoglycemic mice and rats. CGMI, the most potent SGLT1 inhibitor among them, enhanced glucose-induced, but not fat-induced, plasma aGLP-1 increase at a lower dose compared with canagliflozin. Both CGMI and canagliflozin delayed intestinal glucose absorption after oral administration in normoglycemic rats. The combined treatment of canagliflozin and a DPP4 inhibitor increased plasma aGLP-1 levels and improved glucose tolerance compared with single treatment in both 8- and 13-week-old Zucker diabetic fatty rats. These results suggest that transient inhibition of intestinal SGLT1 promotes GLP-1 secretion by delaying glucose absorption and that concomitant inhibition of intestinal SGLT1 and DPP4 is a novel therapeutic option for glycemic control in type 2 diabetes mellitus. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  11. The inhibition of embryonic histone deacetylases as the possible mechanism accounting for axial skeletal malformations induced by sodium salicylate.

    PubMed

    Di Renzo, Francesca; Cappelletti, Graziella; Broccia, Maria Luisa; Giavini, Erminio; Menegola, Elena

    2008-08-01

    In spite of the large use of salicylates, introduced into clinical practice more than 100 years ago, their anti-inflammatory and cancer preventive mechanisms are still under study. Teratogenic effects of salicylates have been reported in experimental animals since 1959 but the pathogenic pathways and the mechanisms of action were never described until now. The aim of this work is to verify if the inhibition of embryonic histone deacetylase (HDAC) enzymes and the consequent tissue hyperacetylation could be the mechanism responsible for axial skeletal defects described after the exposure of pregnant rodents to sodium salicylate (SAL). E8 pregnant CD-1 mice were intraperitoneally treated with SAL 0-150-300-450 mg/kg and sacrificed at 1, 3, 5 h after treatment or at term of gestation (E18). E8 embryos were processed for Western blotting and immunostaining analyses, while skeletons of E18 fetuses were double stained for bone and cartilage. A group of control E8 embryos were used to prepare embryonic nuclear extract for the HDAC enzyme assay. A significant SAL dose-related HDAC inhibition activity, compatible with a mixed-type partial inhibition mechanism, was detected. A clear dose-related hyperacetylation of histones was observed in embryos exposed in utero to SAL, with a peak at 3 h after treatment of dams. The most hyperacetylated organs were somites and the heart. Histone hyperacetylation is suggested to be the mechanism accounting for SAL-related axial skeletal and cardiovascular defects and is proposed as the mechanism responsible for other biological effects of salicylates.

  12. Antimony sulfide thin films prepared by laser assisted chemical bath deposition

    NASA Astrophysics Data System (ADS)

    Shaji, S.; Garcia, L. V.; Loredo, S. L.; Krishnan, B.; Aguilar Martinez, J. A.; Das Roy, T. K.; Avellaneda, D. A.

    2017-01-01

    Antimony sulfide (Sb2S3) thin films were prepared by laser assisted chemical bath deposition (LACBD) technique. These thin films were deposited on glass substrates from a chemical bath containing antimony chloride, acetone and sodium thiosulfate under various conditions of normal chemical bath deposition (CBD) as well as in-situ irradiation of the chemical bath using a continuous laser of 532 nm wavelength. Structure, composition, morphology, optical and electrical properties of the Sb2S3 thin films produced by normal CBD and LACBD were analyzed by X-Ray diffraction (XRD), Raman Spectroscopy, Atomic force microscopy (AFM), X-Ray photoelectron spectroscopy (XPS), UV-vis spectroscopy and Photoconductivity. The results showed that LACBD is an effective synthesis technique to obtain Sb2S3 thin films for optoelectronic applications.

  13. Sodium alginate oligosaccharides from brown algae inhibit Salmonella Enteritidis colonization in broiler chickens.

    PubMed

    Yan, G L; Guo, Y M; Yuan, J M; Liu, D; Zhang, B K

    2011-07-01

    The effects of sodium alginate oligosaccharides (sAO) on growth performance, cecal microbiota, Salmonella translocation to internal organs, and mucosal immune responses to challenge with Salmonella enterica serovar Enteritidis in broiler chickens were investigated. We designed an experiment with a 2 × 3 factorial arrangement, in which 3 feed treatments with supplementation of sAO at 0 (controls), 0.04, or 0.2% were provided in the diet for birds not challenged or challenged with Salmonella Enteritidis. There were 5 randomly placed replicate pens for each treatment. At 8 to 12 d of age, one-half the poults were orally gavaged with 10(8) cfu of Salmonella Enteritidis and the nonchallenged groups were inoculated with sterile PBS. Body weight loss and mortality resulting from Salmonella infection were mitigated by the addition of sAO. Supplementation of sAO at 0.2% was the most effective concentration for reducing Salmonella colonization and increasing the number of lactic acid bacteria in the cecum of chickens challenged with Salmonella Enteritidis. Cecal Salmonella Enteritidis-specific IgA production was significantly increased by sAO at 0.2% at 5 d postchallenge compared with the other treatments and was maintained at higher levels at the 2 dosages of sAO at 10 d postchallenge. With Salmonella Enteritidis challenge, sAO at 0.04% showed an anti-inflammatory effect through upregulation of interleukin (IL)-10 expression in the cecal tonsils. The supplementation level of 0.2% showed dramatic immunostimulatory activity by inducing interferon-γ, IL-10, and IL-1β mRNA expression in cecal tonsils of nonchallenged birds. However, the high level of sAO induced a robust mucosal immune response in the absence of a challenge, and this may have led to a decline in BW. These findings suggest that dietary sAO can decrease Salmonella colonization and improve intestinal barrier function and performance of chickens.

  14. Comparison of sodium acid sulfate to citric acid to inhibit browning of fresh-cut potatoes.

    PubMed

    Calder, Beth L; Kash, Emily A; Davis-Dentici, Katherine; Bushway, Alfred A

    2011-04-01

    Sodium acid sulfate (SAS) dip treatments were evaluated against a distilled water control and citric acid (CA) to compare its effectiveness in reducing enzymatic browning of raw, French-fry cut potatoes. Two separate studies were conducted with dip concentrations ranging from 0%, 1%, and 3% in experiment 1 to 0%, 2%, and 2.5% in experiment 2 to determine optimal dip concentrations. Russet Burbank potatoes were peeled, sliced, and dipped for 1 min and stored at 3 °C. Color, texture, fry surface pH, and microbiological analyses were conducted on days 0, 7, and 14. The 3% SAS- and CA-treated samples had significantly (p<0.0001) lower pH levels on fry surfaces than all other treatments. Both acidulants had significantly (p≤0.05) lower aerobic plate counts compared to controls in both studies by day 7. However, SAS appeared to be the most effective at the 3% level in maintaining a light fry color up to day 14 and had the highest L-values than all other treatments. The 3% SAS-treated fry slices appeared to have the least change in textural properties over storage time, having a significantly (p=0.0002) higher force value (kg force [kgf]) than the other treatments during experiment 1, without any signs of case-hardening that appeared in the control and CA-treated samples. SAS was just as comparable to CA in reducing surface fry pH and also lowering microbial counts over storage time. According to the results, SAS may be another viable acidulant to be utilized in the fresh-cut fruit and vegetable industry.

  15. Nedocromil sodium inhibits antigen-induced contraction of human lung parenchymal and bronchial strips, and the release of sulphidopeptide-leukotriene and histamine from human lung fragments.

    PubMed Central

    Napier, F. E.; Shearer, M. A.; Temple, D. M.

    1990-01-01

    1. The effects of nedocromil sodium on antigen-induced release of sulphidopeptide-leukotrienes and histamine from passively sensitized fragments of human lung, and on antigen-induced contraction of sensitized strips of human lung parenchyma and bronchus, have been studied. 2. Nedocromil sodium 0.1 and 1 microM inhibited leukotriene release from fragments of human lung by 30% and 38% respectively, and histamine release by 43% for both concentrations, but 10 microM was ineffective. The lung fragments, which were passively sensitized to house dust mite, Dermataphagoides pteronyssinus, in control experiments released leukotrienes (6.58 +/- 0.12 nmol equiv. leukotriene C4 per g, n = 6) and histamine (10.3 +/- 1.8 of total tissue histamine, n = 5) when challenged with house dust mite extract. 3. Isolated strips of human lung parenchyma, passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 40% of the maximal histamine response for each strip. Nedocromil sodium 0.1 and 1 microM inhibited these contractions by 50% and 70% of the control response, but 10 microM had no inhibitory effect. 4. Isolated rings from human bronchus, also passively sensitized to D. pteronyssinus, contracted when treated with house dust mite extract to a mean value of 86% of the maximal histamine response. Nedocromil sodium 1 microM, but not 0.1 or 10 microM, inhibited contractions by 48% of the control response. 5. The therapeutic effects of nedocromil sodium in allergic asthma may depend, partly, on its inhibition of antigen-induced release of leukotrienes and histamine in human lung and its consequent inhibition of antigen-induced contractions of parenchymal and bronchial tissue. PMID:1696152

  16. Thin-film antimony-antimony-oxide enzyme electrode for penicillin determination.

    PubMed

    Flanagan, M T; Carroll, N J

    1986-07-01

    A potentiometric penicillinase electrode is reported in which the base pH transducer is a thin-film antimony-antimony-oxide electrode deposited by vacuum evaporation. Several enzyme immobilization procedures have been examined and a crosslinked protein film found to be the most appropriate to this type of sensor. The use of an adjacent antimony-antimony-oxide track as a pseudoreference electrode was successfully demonstrated. The overall response was shown to be independent of the stirring rate above 100 rpm, but the kinetics of the response were found to depend markedly on the stirring rate. The intrinsic linear response range was 3 x 10(-4)M to 7 x 10(-3)M penicillin G. Linearizing transforms that extend the useful range were examined.

  17. Microbial Antimony Biogeochemistry: Enzymes, Regulation, and Related Metabolic Pathways

    PubMed Central

    Li, Jingxin; Wang, Qian; Oremland, Ronald S.; Kulp, Thomas R.; Rensing, Christopher

    2016-01-01

    Antimony (Sb) is a toxic metalloid that occurs widely at trace concentrations in soil, aquatic systems, and the atmosphere. Nowadays, with the development of its new industrial applications and the corresponding expansion of antimony mining activities, the phenomenon of antimony pollution has become an increasingly serious concern. In recent years, research interest in Sb has been growing and reflects a fundamental scientific concern regarding Sb in the environment. In this review, we summarize the recent research on bacterial antimony transformations, especially those regarding antimony uptake, efflux, antimonite oxidation, and antimonate reduction. We conclude that our current understanding of antimony biochemistry and biogeochemistry is roughly equivalent to where that of arsenic was some 20 years ago. This portends the possibility of future discoveries with regard to the ability of microorganisms to conserve energy for their growth from antimony redox reactions and the isolation of new species of “antimonotrophs.” PMID:27342551

  18. Microbial antimony biogeochemistry: Enzymes, regulation, and related metabolic pathways

    USGS Publications Warehouse

    Li, Jingxin; Qian Wang,; Oremland, Ronald S.; Kulp, Thomas R.; Rensing, Christopher; Wang, Gejiao

    2016-01-01

    Antimony (Sb) is a toxic metalloid that occurs widely at trace concentrations in soil, aquatic systems, and the atmosphere. Nowadays, with the development of its new industrial applications and the corresponding expansion of antimony mining activities, the phenomenon of antimony pollution has become an increasingly serious concern. In recent years, research interest in Sb has been growing and reflects a fundamental scientific concern regarding Sb in the environment. In this review, we summarize the recent research on bacterial antimony transformations, especially those regarding antimony uptake, efflux, antimonite oxidation, and antimonate reduction. We conclude that our current understanding of antimony biochemistry and biogeochemistry is roughly equivalent to where that of arsenic was some 20 years ago. This portends the possibility of future discoveries with regard to the ability of microorganisms to conserve energy for their growth from antimony redox reactions and the isolation of new species of “antimonotrophs.”

  19. Open-channel block by internally applied amines inhibits activation gate closure in batrachotoxin-activated sodium channels.

    PubMed Central

    Zamponi, G W; French, R J

    1994-01-01

    We have studied the action of several pore-blocking amines on voltage-dependent activation gating of batrachotoxin(BTX)-activated sodium channels, from bovine heart and rat skeletal muscle, incorporated into planar lipid bilayers. Although structurally simpler, the compounds studied show general structural features and channel-inhibiting actions that resemble those of lidocaine. When applied to the cytoplasmic end of the channel, these compounds cause a rapid, voltage-dependent, open-channel block seen as a reduction in apparent single-channel amplitude (companion paper). Internal application of phenylpropanolamine, phenylethylamine, phenylmethylamine, and diethylamine, as well as causing open-channel block, reduces the probability of channel closure, producing a shift of the steady-state activation curve toward more hyperpolarizing potentials. These gating effects were observed for both cardiac and skeletal muscle channels and were not evoked by addition of equimolar N-Methyl-D-Glucamine, suggesting a specific interaction of the blockers with the channel rather than a surface charge effect. Kinetic analysis of phenylpropanolamine action on skeletal muscle channels indicated that phenylpropanolamine reduced the closed probability via two separate mechanisms. First, mean closed durations were slightly abbreviated in its presence. Second, and more important, the frequency of the gating closures was reduced. This action was correlated with the degree, and the voltage dependence, of open-channel block, suggesting that the activation gate cannot close while the pore is occluded by the blocker. Such a mechanism might underlie the previously reported immobilization of gating charge associated with local anesthetic block of unmodified sodium channels. PMID:7811914

  20. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus.

    PubMed

    Cherney, David Z I; Perkins, Bruce A; Soleymanlou, Nima; Maione, Maria; Lai, Vesta; Lee, Alana; Fagan, Nora M; Woerle, Hans J; Johansen, Odd Erik; Broedl, Uli C; von Eynatten, Maximilian

    2014-02-04

    The primary objective of this mechanistic open-label, stratified clinical trial was to determine the effect of 8 weeks' sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus (T1D). Inulin (glomerular filtration rate; GFR) and paraaminohippurate (effective renal plasma flow) clearances were measured in individuals stratified based on having hyperfiltration (T1D-H, GFR ≥ 135 mL/min/1.73m(2), n=27) or normal GFR (T1D-N, GFR 90-134 mL/min/1.73m(2), n=13) at baseline. Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic (4-6 mmol/L) and hyperglycemic (9-11 mmol/L) conditions at baseline and end of treatment. During clamped euglycemia, hyperfiltration was attenuated by -33 mL/min/1.73m(2) with empagliflozin in T1D-H, (GFR 172±23-139±25 mL/min/1.73 m(2), P<0.01). This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance (all P<0.01). Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia. In T1D-N, GFR, other renal function parameters, and plasma NO were not altered by empagliflozin. Empagliflozin reduced hemoglobin A1c significantly in both groups, despite lower insulin doses in each group (P≤0.04). In conclusion, short-term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin attenuated renal hyperfiltration in subjects with T1D, likely by affecting tubular-glomerular feedback mechanisms. http://www.clinicaltrials.gov. Unique identifier: NCT01392560.

  1. Sodium glucose transporter 2 (SGLT2) inhibition with empagliflozin improves cardiac diastolic function in a female rodent model of diabetes.

    PubMed

    Habibi, Javad; Aroor, Annayya R; Sowers, James R; Jia, Guanghong; Hayden, Melvin R; Garro, Mona; Barron, Brady; Mayoux, Eric; Rector, R Scott; Whaley-Connell, Adam; DeMarco, Vincent G

    2017-01-13

    Obese and diabetic individuals are at increased risk for impairments in diastolic relaxation and heart failure with preserved ejection fraction. The impairments in diastolic relaxation are especially pronounced in obese and diabetic women and predict future cardiovascular disease (CVD) events in this population. Recent clinical data suggest sodium glucose transporter-2 (SGLT2) inhibition reduces CVD events in diabetic individuals, but the mechanisms of this CVD protection are unknown. To determine whether targeting SGLT2 improves diastolic relaxation, we utilized empagliflozin (EMPA) in female db/db mice. Eleven week old female db/db mice were fed normal mouse chow, with or without EMPA, for 5 weeks. Blood pressure (BP), HbA1c and fasting glucose were significantly increased in untreated db/db mice (DbC) (P < 0.01). EMPA treatment (DbE) improved glycemic indices (P < 0.05), but not BP (P > 0.05). At baseline, DbC and DbE had already established impaired diastolic relaxation as indicated by impaired septal wall motion (>tissue Doppler derived E'/A' ratio) and increased left ventricular (LV) filling pressure (sodium channel (ENaC), and the development of these abnormalities were reduced with EMPA. DbC exhibited eccentric LV hypertrophy that was slightly improved by EMPA, indicated by a reduction in cardiomyocyte cross sectional area. In summary, EMPA improved glycemic indices along with diastolic relaxation, as well as SGK1/ENaC profibrosis signaling and associated interstitial fibrosis, all of which occurred in the absence of any changes in BP.

  2. Imipramine exploits histone deacetylase 11 to increase the IL-12/IL-10 ratio in macrophages infected with antimony-resistant Leishmania donovani and clears organ parasites in experimental infection.

    PubMed

    Mukherjee, Sandip; Mukherjee, Budhaditya; Mukhopadhyay, Rupkatha; Naskar, Kshudiram; Sundar, Shyam; Dujardin, Jean-Claude; Roy, Syamal

    2014-10-15

    The efflux of antimony through multidrug resistance protein (MDR)-1 is the key factor in the failure of metalloid treatment in kala-azar patients infected with antimony-resistant Leishmania donovani (Sb(R)LD). Previously we showed that MDR-1 upregulation in Sb(R)LD infection is IL-10-dependent. Imipramine, a drug in use for the treatment of depression and nocturnal enuresis in children, inhibits IL-10 production from Sb(R)LD-infected macrophages (Sb(R)LD-Mϕs) and favors accumulation of surrogates of antimonials. It inhibits IL-10-driven nuclear translocation of c-Fos/c-Jun, critical for enhanced MDR-1 expression. The drug upregulates histone deacetylase 11, which inhibits acetylation of IL-10 promoter, leading to a decrease in IL-10 production from Sb(R)LD-Mϕs. It abrogates Sb(R)LD-mediated p50/c-Rel binding to IL-10 promoter and preferentially recruits p65/RelB to IL-12 p35 and p40 promoters, causing a decrease in IL-10 and overproduction of IL-12 in Sb(R)LD-Mϕs. Histone deacetylase 11 per se does not influence IL-12 promoter activity. Instead, a imipramine-mediated decreased IL-10 level allows optimal IL-12 production in Sb(R)LD-Mϕs. Furthermore, exogenous rIL-12 inhibits intracellular Sb(R)LD replication, which can be mimicked by the presence of Ab to IL-10. This observation indicated that reciprocity exists between IL-10 and IL-12 and that imipramine tips the balance toward an increased IL-12/IL-10 ratio in Sb(R)LD-Mϕs. Oral treatment of infected BALB/c mice with imipramine in combination with sodium stibogluconate cleared organ Sb(R)LD parasites and caused an expansion of the antileishmanial T cell repertoire where sodium stibogluconate alone had no effect. Our study deciphers a detailed molecular mechanism of imipramine-mediated regulation of IL-10/IL-12 reciprocity and its impact on Sb(R)LD clearance from infected hosts.

  3. Sulfonylurea receptors inhibit the epithelial sodium channel (ENaC) by reducing surface expression.

    PubMed

    Konstas, A A; Bielfeld-Ackermann, A; Korbmacher, C

    2001-08-01

    In the kidney the epithelial Na+ channel (ENaC) is co-expressed with the sulfonylurea receptor (SUR), an ABC protein that shares a high degree of homology with the cystic fibrosis transmembrane conductance regulator (CFTR) and reportedly modifies ENaC in various preparations. To investigate a possible regulatory relationship between SUR and ENaC, we performed co-expression studies on Xenopus laevis oocytes, which were assayed for amiloride-sensitive currents (DeltaIami). Moreover, a chemiluminescence assay was used to investigate the surface expression of extracellular hemagglutinin-tagged SUR1 (SUR1-HA) or HA-tagged ENaC (ENaC-HA). In oocytes co-injected with SUR1/ENaC (or SUR2B/ENaC) DeltaIami was reduced by congruent with 53% (or congruent with 45%) compared to DeltaIami measured in matched control oocytes injected with ENaC alone. The inhibitory effect of SUR on DeltaIami was preserved in oocytes expressing ENaC with C-terminally truncated subunits. Co-expression of SURs did not confer sensitivity of DeltaIami to diazoxide, pinacidil, tolbutamide, or glibenclamide. ENaC does not facilitate the surface expression of SUR1-HA, which is known to be retained in the endoplasmatic reticulum (ER) by an ER-retention/retrieval signal. SUR1-HAAAA, a mutant that lacks this signal, still inhibits ENaC currents. Chemiluminescence was reduced by congruent with 49% in oocytes co-expressing ENaC-HA/SUR1 compared to that in control oocytes expressing ENaC-HA alone. We conclude that SUR does not interact with ENaC at the level of the plasma membrane but that it inhibits DeltaIami by reducing surface expression of the channel.

  4. [Oxidation of gold-antimony ores by a thermoacidophilic microbial consortium].

    PubMed

    Tsaplina, I A; Sorokin, V V; Zhuravleva, A E; Melamud, V S; Bogdanova, T I; Kondrat'eva, T F

    2013-01-01

    Antimony leaching from sulfide ore samples by an experimental consortium of thermoacidophilic microorganisms, including Sulfobacillus, Leptospirillum, and Ferroplasma strains was studied. The ores differed significantly in the content of the major metal sulfides (%): Sb(S), 0.84 to 29.95; Fe(S), 0.47 to 2.5, and As(S), 0.01 to 0.4. Independent on the Sb(S) concentration in the experimental sample, after adaptation to a specific ore and pulp compaction the microorganisms grew actively and leached/oxidized all gold-antimony ores at 39 ± 1 degrees C. The lower was the content of iron and arsenic sulfides, the higher was antimony leaching. For the first time the investigations conducted with the use of X-ray microanalysis research made it possible to conclude that in a natural high-antimony ore Sb inhibits growth of only a part of the cell population and that Ca, Fe, and Sb may compete for the binding centers of the cell.

  5. Soluble Epoxide Hydrolase Deficiency Inhibits Dextran Sulfate Sodium-induced Colitis and Carcinogenesis in Mice

    PubMed Central

    DONG, HUA; LIAO, JIE; HAMMOCK, BRUCE D.; YANG, GUANG-YU

    2014-01-01

    Soluble epoxide hydrolase (sEH) hydrolyses/inactivates anti-inflammatory epoxyeicosatrienoic acids (EETs) to their corresponding diols, and targeting sEH leads to strong anti-inflammatory effects. In the present study, using a tissue microarray and immunohistochemical approach, a significant increase of sEH expression was identified in ulcerative colitis (UC)-associated dysplasia and adenocarcinoma. The effects of deficiency in the sEH gene were determined on dextran sulfate sodium (DSS) colitis-induced carcinogenesis. The effects of EETs on lipopolysaccharide (LPS)-activated macrophages were analyzed in vitro. With extensive histopathological and immunohistochemical analyses, compared to wild-type mice, sEH−/− mice exhibited a significant decrease in tumor incidence (13/20 vs. 6/19, p<0.05) and a markedly reduced average tumor size (59.62±20.91 mm3 vs. 22.42±11.22 mm3), and a significant number of pre-cancerous dysplasia (3±1.18 vs. 2±0.83, p<0.01). The inflammatory activity, as measured by the extent/proportion of erosion/ulceration/dense lymphoplasmacytosis (called active colitis index) in the colon, was significantly lower in sEH−/− mice (44.7%±24.9% vs. 20.2%±16.2%, p<0.01). The quantitative polymerase chain reaction (qPCR) assays demonstrated significantly low levels of cytokines/chemokines including monocyte chemoattractant protein (MCP-1), inducible nitric oxide synthase (iNOS), vasopressin-activated calcium-mobilizing (VCAM-1), interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). In vitro, LPS-activated macrophages treated with 14,15-EET showed a significant reduction of LPS-triggered IL-1β and TNF-α expression. Eicosanoic acid metabolic profiling revealed a significant increase of the ratios of EETs/dihydroeicosatrienoic acids (DHETs) and epoxyoctadecennoic acid/dihydroxyoctadecenoic acid (EpOMEs/DiHOMEs). These results indicate that sEH plays an important role in the development of colitis and in inducing carcinogenesis

  6. Keratinocyte Growth Factor Combined with a Sodium Hyaluronate Gel Inhibits Postoperative Intra-Abdominal Adhesions

    PubMed Central

    Wei, Guangbing; Zhou, Cancan; Wang, Guanghui; Fan, Lin; Wang, Kang; Li, Xuqi

    2016-01-01

    Postoperative intra-abdominal adhesion is a very common complication after abdominal surgery. One clinical problem that remains to be solved is to identify an ideal strategy to prevent abdominal adhesions. Keratinocyte growth factor (KGF) has been proven to improve the proliferation of mesothelial cells, which may enhance fibrinolytic activity to suppress postoperative adhesions. This study investigated whether the combined administration of KGF and a sodium hyaluronate (HA) gel can prevent intra-abdominal adhesions by improving the orderly repair of the peritoneal mesothelial cells. The possible prevention mechanism was also explored. The cecum wall and its opposite parietal peritoneum were abraded after laparotomy to induce intra-abdominal adhesion formation. Animals were randomly allocated to receive topical application of HA, KGF, KGF + HA, or normal saline (Control). On postoperative day 7, the adhesion score was assessed with a visual scoring system. Masson’s trichrome staining, picrosirius red staining and hydroxyproline assays were used to assess the magnitude of adhesion and tissue fibrosis. Cytokeratin, a marker of the mesothelial cells, was detected by immunohistochemistry. The levels of tissue plasminogen activator (tPA), interleukin-6 (IL-6), and transforming growth factor β1 (TGF-β1) in the abdominal fluid were determined using enzyme-linked immunosorbent assays (ELISAs). Western blotting was performed to examine the expression of the TGF-β1, fibrinogen and α-smooth muscle actin (α-SMA) proteins in the rat peritoneal adhesion tissue. The combined administration of KGF and HA significantly reduced intra-abdominal adhesion formation and fibrin deposition and improved the orderly repair of the peritoneal mesothelial cells in the rat model. Furthermore, the combined administration of KGF and HA significantly increased the tPA levels but reduced the levels of IL-6, tumor necrosis factor α (TNF-α) and TGF-β1 in the abdominal fluid. The expression

  7. Separation of Lead from Crude Antimony by Pyro-Refining Process with NaPO3 Addition

    NASA Astrophysics Data System (ADS)

    Ye, Longgang; Hu, Yuejie; Xia, Zhimei; Chen, Yongming

    2016-06-01

    The main purpose of this study was to separate lead from crude antimony through an oxidation pyro-refining process and by using sodium metaphosphate as a lead elimination reagent. The process parameters that will affect the refining results were optimized experimentally under controlled conditions, such as the sodium metaphosphate charging dosage, the refining temperature and duration, and the air flow rate, to determine their effect on the lead content in refined antimony and the lead removal rate. A minimum lead content of 0.0522 wt.% and a 98.6% lead removal rate were obtained under the following optimal conditions: W_{{{NaPO}_{{3}} }} = 15% W Sb (where W represents weight), a refining temperature of 800°C, a refining time of 30 min, and an air flow rate of 3 L/min. X-ray diffractometry and scanning electron microscopy showed that high-purity antimony was obtained. The smelting operation is free from smoke or ammonia pollution when using monobasic sodium phosphate or ammonium dihydrogen phosphate as the lead elimination reagent. However, this refining process can also remove a certain amount of sulfur, cobalt, and silicon simultaneously, and smelting results also suggest that sodium metaphosphate can be used as a potential lead elimination reagent for bismuth and copper refining.

  8. Natural attenuation processes applying to antimony: a study in the abandoned antimony mine in Goesdorf, Luxembourg.

    PubMed

    Filella, Montserrat; Philippo, Simon; Belzile, Nelson; Chen, Yuwei; Quentel, François

    2009-12-01

    The processes leading to the attenuation of the antimony concentration in the water draining from the abandoned antimony mine in Goesdorf, Luxembourg, have been studied. Antimony has been mined in Goesdorf since Roman times from a stibnite-rich mesothermal vein system hosted in metasedimentary schist. The draining waters have pH values between 7 and 8 because the mineralization itself contains calcite and dolomite. This study combines the identification of minerals in the supergene zone with the application of bulk techniques (e.g., measurement of antimony in the waters of the adit and the creek draining the mine, sediment sequential extractions) over a period of five years. Antimony concentrations in the water that leaves the supergene zone are controlled by the dissolution of stibnite and the subsequent formation of Sb(III) oxides and sulphates. The relative proportions of the main secondary minerals can be qualitatively estimated as follows: 70% valentinite, 15% senarmontite and 12% sulphates (coquandite, klebelsbergite and peretaite). Further antimony attenuation along the adit and the creek that drain the mine waters is due partly to dilution, through mixing with waters that have not been in contact with the ore, and partly to sorption onto amorphous iron and manganese oxides present in the colluvial sediments.

  9. Meglumine Antimoniate (Glucantime) Causes Oxidative Stress-Derived DNA Damage in BALB/c Mice Infected by Leishmania (Leishmania) infantum.

    PubMed

    Moreira, Vanessa Ribeiro; de Jesus, Luís Cláudio Lima; Soares, Rossy-Eric Pereira; Silva, Luis Douglas Miranda; Pinto, Bruno Araújo Serra; Melo, Maria Norma; Paes, Antonio Marcus de Andrade; Pereira, Silma Regina Ferreira

    2017-06-01

    Leishmaniasis is a neglected tropical disease caused by >20 species of the protozoan parasite Leishmania Meglumine antimoniate (Glucantime) is the first-choice drug recommended by the World Health Organization for the treatment of all types of leishmaniasis. However, the mechanisms of action and toxicity of pentavalent antimonials, including genotoxic effects, remain unclear. Therefore, the mechanism by which meglumine antimoniate causes DNA damage was investigated for BALB/c mice infected by Leishmania (Leishmania) infantum and treated with meglumine antimoniate (20 mg/kg for 20 days). DNA damage was analyzed by a comet assay using mouse leukocytes. Furthermore, comet assays were followed by treatment with formamidopyrimidine-DNA glycosylase and endonuclease III, which remove oxidized DNA bases. In addition, the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the animals' sera were assessed. To investigate mutagenicity, we carried out a micronucleus test. Our data demonstrate that meglumine antimoniate, as well as L. infantum infection, induces DNA damage in mammalian cells by the oxidation of nitrogenous bases. Additionally, the antileishmanial increased the frequency of micronucleated cells, confirming its mutagenic potential. According to our data, both meglumine antimoniate treatment and L. infantum infection promote oxidative stress-derived DNA damage, which promotes overactivation of the SOD-CAT axis, whereas the SOD-GPx axis is inhibited as a probable consequence of glutathione (GSH) depletion. Finally, our data enable us to suggest that a meglumine antimoniate regimen, as recommended by the World Health Organization, would compromise GPx activity, leading to the saturation of antioxidant defense systems that use thiol groups, and might be harmful to patients under treatment. Copyright © 2017 American Society for Microbiology.

  10. Arsenic and Antimony Transporters in Eukaryotes

    PubMed Central

    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. PMID:22489166

  11. Arsenic and antimony transporters in eukaryotes.

    PubMed

    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.

  12. The Diffusion of Antimony of Alpha Iron.

    DTIC Science & Technology

    Diffusion coefficients of antimony in alpha iron were determined in the temperature range 700 to 900C using the residual activity method. Specimens...negligible effect on the diffusion of antomony in alpha iron . These results are discussed in relation to the phenomenon of temper brittleness in steels

  13. Inhibition of nitrite-induced toxicity in channel catfish by calcium chloride and sodium chloride

    USGS Publications Warehouse

    Tommasso J.R., Wright; Simco, B.A.; Davis, K.B.

    1980-01-01

    Environmental chloride has been shown to inhibit methemoglobin formation in fish, thereby offering a protective effect against nitrite toxicity. Channel catfish (Ictalurus punctatus) were simultaneously exposed to various environmental nitrite and chloride levels (as either CaCl2 or NaCl) in dechlorinated tap water (40 mg/L total hardness, 47 mg/L alkalinity, 4 mg/L chloride, pH = 6.9-7.1, and temperature 21-24°C). Methemoglobin levels in fish simultaneously exposed to 2.5 mg/L nitrite and up to 30 mg/L chloride as either CaCl2 or NaCl were similar but significantly lower than in unprotected fish. Exposure to 10 mg/L nitrite and 60 mg/L chloride resulted in methemoglobin levels similar to those of the controls; most unprotected fish died. Fish exposed to 10 mg/L nitrite had significantly lower methemoglobin levels when protected with 15.0 mg/L chloride as CaCl2 than with NaCl. Fish exposed to nitrite in the presence of 60 mg/L chloride (as either CaCl2 or NaCl) had similar 24-h LC50 values that were significantly elevated above those obtained in the absence of chloride. Calcium had little effect on tolerance to nitrite toxicity in channel catfish in contrast to its large effect reported in steelhead trout (Salmo gairdneri).

  14. EP3 receptors inhibit antidiuretic-hormone-dependent sodium transport across frog skin epithelium.

    PubMed

    Rytved, K A; Nielsen, R

    1999-01-01

    We examined the effect of prostaglandin E2 (PGE2) on antidiuretic hormone (ADH)-dependent Na+ transport and cAMP production in isolated frog skin epithelium. ADH caused an increase in transepithelial Na+ transport and a decrease in cellular potential, indicating an increase in apical Na+ permeability. Subsequent addition of PGE2 decreased Na+ transport and repolarised the cells. The PGE2 receptor EP1/3-selective analogue sulprostone and the PGE2 receptor EP2/3-selective analogue misoprostol were able to mimic the effect of PGE2. ADH increased cellular cAMP levels, whereas PGE2, sulprostone and misoprostol were able to reduce the ADH-dependent cAMP production. Measurements of intracellular Ca2+ concentration ([Ca2+]i) revealed that it was unaffected by both PGE2 and sulprostone. The inhibitory effect of PGE2 on ADH-dependent Na+ transport was also observed in Ca2+-depleted epithelia. We conclude that ADH stimulates transepithelial Na+ transport by increasing cellular cAMP levels, whereas PGE2 inhibits ADH-dependent Na+ transport by activating EP3-type receptors, which decrease cellular cAMP levels. We have found no evidence that [Ca2+]i is involved in the regulation of ADH-dependent Na+ transport by PGE2.

  15. Dietary sodium restriction specifically potentiates left ventricular ACE inhibition by zofenopril, and is associated with attenuated hypertrophic response in rats with myocardial infarction.

    PubMed

    Westendorp, Bart; Schoemaker, Regien G; Buikema, Hendrik; de Zeeuw, Dick; van Veldhuisen, Dirk J; van Gilst, Wiek H

    2004-03-01

    In patients with myocardial infarction (MI)-induced heart failure, angiotensin-converting enzyme (ACE) inhibitors are proven effective therapy in inhibiting the progression towards overt heart failure. However, the prognosis in these patients is still very poor, and optimisation of therapy is warranted. The antihypertensive and renoprotective effects of ACE inhibitors (ACE-Is) can be substantially enhanced by dietary sodium restriction. In line with the latter, the aim of the present study was to explore whether dietary sodium restriction enhances the efficacy of ACE-I after MI. Rats with MI-induced left ventricular (LV) dysfunction received ACE-I therapy with zofenopril (5.5 mg/kg/day orally), with or without dietary sodium restriction. ACE activity was measured in non-infarcted LV tissue, kidneys and plasma. Effects on cardiac hypertrophy were examined by means of organ weight/body weight ratios. After blood pressure (BP) measurements, functional consequences of therapy were evaluated as LV pressure development in isolated perfused hearts. Dietary sodium restriction alone had no effect on any of the measured parameters, whereas zofenopril alone significantly reduced plasma and kidney ACE activity, but not LV ACE activity, nor LV weight/body weight ratio. However, only when ACE-I therapy was combined with dietary sodium restriction was LV ACE activity significantly reduced. This effect was paralleled by inhibition of LV hypertrophy. BP was reduced after infarction, and further reduced by zofenopril, but not affected by dietary sodium. Neither treatment was associated with effects on the MI-induced reduction of LV function in vitro. Effects of ACE inhibition with zofenopril can be potentiated by additional dietary sodium restriction. However, these effects were tissue-specific, since LV, but not kidney or plasma, ACE activity was affected by the additional dietary sodium restriction. Effects on LV ACE activity were paralleled by reduced LV hypertrophy. Since the

  16. Inhibition of the catalase activity from Phaseolus vulgaris and Medicago sativa by sodium chloride.

    PubMed

    Tejera García, Noel A; Iribarne, Carmen; Palma, Francisco; Lluch, Carmen

    2007-08-01

    Changes in catalase activity during the development of the Rhizobium-legume symbiosis as well as its response in salinized plants of Phaseolus vulgaris and Medicago sativa, was studied. Besides, it was examined the behavior of the enzyme, isolated from leaves and root nodules, during in vitro incubation with NaCl doses. Nodule catalase activities of both legumes were assayed with several enzyme inhibitors and also purified. Leaf catalase activity of Phaseolus vulgaris and Medicago sativa decreased and increased respectively throughout the ontogeny, but root nodule catalase kept a high and stable value. This last result suggests that both legumes require the maintenance of high nodule catalase in nitrogen-fixing nodules. Under salt stress conditions leaf and nodule catalase activity decreased in both, grain and pasture legumes. Because catalase from leaf of Medicago sativa and nodules of Phaseolus vulgaris were relatively sensitive to NaCl during in vitro experiments, the detoxifying role of this enzyme for H(2)O(2) should be limited in such conditions. Both catalases, from determinate and indeterminate nodules, were affected neither by oxygen nor superoxide radicals but showed a strong (Phaseolus vulgaris) or partial (Medicago sativa) inhibition with dithiothreitol, dithionite and beta-mercaptoethanol. Besides, cyanide was the most potent inhibitor of nodule catalases. Finally, catalases partially purified by immobilized metal ion affinity chromatography migrated at 42 (Phaseolus vulgaris) and 46kDa (Medicago sativa) on SDS-PAGE, whereas native forms on sephacryl S-300 columns exhibited a molecular mass of 59 and 48kDa (Phaseolus vulgaris) and 88 and 53kDa (Medicago sativa).

  17. Cromolyn sodium prophylaxis inhibits pulmonary proinflammatory cytokines in infants at high risk for bronchopulmonary dysplasia.

    PubMed

    Viscardi, R M; Hasday, J D; Gumpper, K F; Taciak, V; Campbell, A B; Palmer, T W

    1997-11-01

    An imbalance of proinflammatory cytokines such as TNF-alpha, IL-1 beta, and the neutrophil chemotactic factor IL-8 and inhibitors (e.g., soluble TNF receptors and IL-1ra) in the lung during the first week of life may contribute to prolonged pulmonary inflammation and fibrosis in bronchopulmonary dysplasia (BPD). Disodium cromoglycate (DSCG) has anti-inflammatory effects in asthma, a disease with many similarities with BPD. In a prospective, randomized, blinded study, we examined whether early DSCG therapy inhibits proinflammatory cytokines in infants at risk for BPD. Twenty-six infants who were identified as high risk (> or = 75% probability) for oxygen-dependency at 28 d by a 12-h predictive score and survived 48 h were randomized to nebulized DSCG 20 mg (n = 13) or 2 cc NS (control, n = 13) every 6 h from Day 3 to Day 28. Lung lavage was collected on Day 3 (pre-study) and Day 7 and analyzed for cell count and differential and TNF-alpha, sTNFR1, sTNFR2, IL-1 beta, IL-1ra, and IL-8 concentrations. The groups' pre-study lavage cytokine concentrations were similar, but TNF-alpha and IL-8 concentrations were 3.6- and 4.9-fold lower in the DSCG group on Day 7 compared with levels in the control group. Soluble TNF receptors were unaffected by DSCG. There was a trend towards lower IL-1 beta levels in DSCG-treated infants on Day 7, but IL-1ra levels were unaffected by DSCG therapy. Three control subjects, but no DSCG-treated infants, died during the study period (p = 0.07). There were no significant differences between survivors of the two groups for oxygen-dependency at 28 d (100% control subjects; 85% DSCG). These results suggest that nebulized DSCG may exert an anti-inflammatory effect in the lungs of infants < or = 1,000 g at risk for BPD.

  18. Blockade of voltage-gated sodium channels inhibits invasion of endocrine-resistant breast cancer cells.

    PubMed

    Mohammed, Fatima H; Khajah, Maitham A; Yang, Ming; Brackenbury, William J; Luqmani, Yunus A

    2016-01-01

    Voltage-gated Na+ channels (VGSCs) are membrane proteins which are normally expressed in excitable cells but have also been detected in cancer cells, where they are thought to be involved in malignancy progression. In this study we examined the ion current and expression profile of VGSC (Nav1.5) in estrogen receptor (ER)-positive (MCF-7) and silenced (pII) breast cancer cells and its possible influence on their proliferation, motility and invasion. VGSC currents were analysed by whole cell patch clamp recording. Nav1.5 expression and localization, in response to EGF stimulation, was examined by western blotting and immunofluorescence respectively. Cell invasion (under-agarose and Matrigel assays), motility (wound healing assay) and proliferation (MTT assay) were assessed in pII cells in response to VGSC blockers, phenytoin (PHT) and tetrodotoxin (TTX), or by siRNA knockdown of Nav1.5. The effect of PHT and TTX on modulating EGF-induced phosphorylation of Akt and ERK1/2 was determined by western blotting. Total matrix metalloproteinase (MMP) was determined using a fluorometric-based activity assay. The level of various human proteases was detected by using proteome profiler array kit. VGSC currents were detected in pII cells, but were absent in MCF-7. Nav1.5 showed cytoplasmic and perinuclear expression in both MCF-7 and pII cells, with enhanced expression upon EGF stimulation. Treatment of pII cells with PHT, TTX or siRNA significantly reduced invasion towards serum components and EGF, in part through reduction of P-ERK1/2 and proteases such as cathepsin E, kallikrein-10 and MMP-7, as well as total MMP activity. At high concentrations, PHT inhibited motility while TTX reduced cell proliferation. Pharmacological or genetic blockade of Nav1.5 may serve as a potential anti-metastatic therapy for breast cancer.

  19. Inhibition of store-operated Ca2+ entry counteracts the apoptosis of nasopharyngeal carcinoma cells induced by sodium butyrate

    PubMed Central

    Huang, Wei; Ren, Caiping; Huang, Guoling; Liu, Jie; Liu, Weidong; Wang, Lei; Zhu, Bin; Feng, Xiangling; Shi, Jia; Li, Jinlong; Xia, Xiaomeng; Jia, Wei; Chen, Jiawen; Chen, Yuxiang; Jiang, Xingjun

    2017-01-01

    Sodium butyrate (NaBu), a histone deacetylase inhibitor, has demonstrated anti-tumor effects in several cancers, and is a promising candidate chemotherapeutic agent. However, its roles in nasopharyngeal carcinoma (NPC), an endemic malignant disease in Southern China and Southeast Asia, has rarely been studied. In the present study, MTT assay, colony formation assay, flow cytometry analysis and western blotting were performed to explore the influence of NaBu on NPC cells and its underlying mechanism. NaBu induced morphological changes and inhibited proliferation in 5–8F and 6–10B cells. MTT assay revealed that NaBu was cytotoxic to 5–8F and 6–10B cells in a dose- and time-dependent manner. Furthermore, flow cytometry analysis revealed that NaBu induced obvious cell apoptosis in 5–8F and 6–10B cells due to the activation of the mitochondrial apoptosis axis. In addition, flow cytometry analysis and western blotting demonstrated that NaBu could enhance the Ca2+ influx by promoting store-operated Ca2+ entry (SOCE) in 5–8F and 6–10B cells. Inhibition of SOCE by specific inhibitors or downregulated expression of calcium release-activated calcium channel protein 1 and stromal interaction molecule 1 could counteract the apoptosis of NPC cells induced by NaBu. Thus, the current study revealed that enhanced SOCE and activated mitochondrial apoptosis axis may account for the mechanisms of cytotoxicity of NaBu in NPC cells, and that NaBu serves as a promising chemotherapeutic agent in NPC therapy. PMID:28356979

  20. [Sodium butyrate inhibits HMGB1 expression and release and attenuates concanavalin A-induced acute liver injury in mice].

    PubMed

    Gong, Quan; Chen, Mao-Jian; Wang, Chao; Nie, Hao; Zhang, Yan-Xiang; Shu, Ke-Gang; Li, Gang

    2014-10-25

    The purpose of the present study is to explore the protective effects of sodium butyrate (SB) pretreatment on concanavalin A (Con A)-induced acute liver injury in mice. The model animals were first administered intraperitoneally with SB. Half an hour later, acute liver injury mouse model was established by caudal vein injection with Con A (15 mg/kg). Then, levels of serous alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using standard clinical method by an automated chemistry analyzer, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured by ELISA, and pathological changes in hepatic tissue were observed by using HE staining and light microscopy. The expression and release of high-mobility group box 1 (HMGB1) were assessed by using reverse transcription polymerase chain reaction (RT-PCR), immunohistochemistry and ELISA. The results showed that the pretreatment of SB significantly protected Con A-treated mice from liver injury as evidenced by the decrease of serum ALT, AST (P < 0.01) and reduction of hepatic tissues necrosis. SB also decreased levels of serous TNF-α and IFN-γ (P < 0.01). Furthermore, the expression and release of HMGB1 were markedly inhibited by SB pretreatment (P < 0.05 or P < 0.01). These results suggest that the attenuating effect of SB on Con A-induced acute liver injury may be due to its role of reducing the TNF-α and IFN-γ production, and inhibiting HMGB1 expression and release.

  1. Selective inhibition of sodium-calcium exchanger by SEA-0400 decreases early and delayed after depolarization in canine heart.

    PubMed

    Nagy, Zsolt A; Virág, László; Tóth, András; Biliczki, Péter; Acsai, Károly; Bányász, Tamás; Nánási, Péter; Papp, Julius Gy; Varró, András

    2004-12-01

    The sodium-calcium exchanger (NCX) was considered to play an important role in arrhythmogenesis under certain conditions such as heart failure or calcium overload. In the present study, the effect of SEA-0400, a selective inhibitor of the NCX, was investigated on early and delayed afterdepolarizations in canine ventricular papillary muscles and Purkinje fibres by applying conventional microelectrode techniques at 37 degrees C. The amplitude of both early and delayed afterdepolarizations was markedly decreased by 1 microM SEA-0400 from 26.6+/-2.5 to 14.8+/-1.8 mV (n=9, P<0.05) and from 12.5+/-1.7 to 5.9+/-1.4 mV (n=3, P<0.05), respectively. In enzymatically isolated canine ventricular myocytes, SEA-0400 did not change significantly the L-type calcium current and the intracellular calcium transient, studied using the whole-cell configuration of the patch-clamp technique and Fura-2 ratiometric fluorometry. It is concluded that, through the reduction of calcium overload, specific inhibition of the NCX current by SEA-0400 may abolish triggered arrhythmias.

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

    PubMed Central

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

    2015-01-01

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

  3. Sodium houttuyfonate inhibits inflammation by blocking the MAPKs/NF-κB signaling pathways in bovine endometrial epithelial cells.

    PubMed

    Zhu, Qi; Xu, Xiaolong; Liu, Xiaoxi; Lin, Jiabao; Kan, Yao; Zhong, Yougang; Liu, Fenghua; Xu, Jianqin

    2015-06-01

    Sodium houttuyfonate (SH) has traditionally been used for the therapy of inflammatory diseases. In this research, we tried to assess the anti-inflammatory effects of SH on LPS-induced bovine endometrial epithelial cell (bEEC) inflammation. SH cell toxicity was measured using the MTT and LDH assays, and inflammatory cytokine expression was assessed by ELISA, qRT-PCR and Western blotting. We demonstrated that SH was not cytotoxic to bEECs, and that it significantly decreased the LPS-induced mRNA and protein expression of tumor necrosis factor (TNF) α, interleukin (IL)-1β, IL-6 and IL-8. Furthermore, in LPS-induced bEECs, SH inhibited IκBα degradation and NF-κB p65 phosphorylation, and suppressed the phosphorylation of the mitogen-activated protein kinases (MAPKs), p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). In conclusion, we found that SH could effectively block the NF-κB-mediated signaling pathway and reduce the inflammatory process, thereby exerting a protective effect on bEECs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Phenolic acids isolated from the fungus Schizophyllum commune exert analgesic activity by inhibiting voltage-gated sodium channels.

    PubMed

    Yao, Hui-Min; Wang, Gan; Liu, Ya-Ping; Rong, Ming-Qiang; Shen, Chuan-Bin; Yan, Xiu-Wen; Luo, Xiao-Dong; Lai, Ren

    2016-09-01

    The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune (SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography (TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance (NMR). The effects of these compounds on voltage-gated sodium (NaV) channels were evaluated using patch clamp. The analgesic activity of these compounds was tested in two types of mouse pain models induced by noxious chemicals. Five phenolic acids identified from SC extracts in the present study included vanillic acid, m-hydroxybenzoic acid, o-hydroxybenzeneacetic acid, 3-hydroxy-5-methybenzoic acid, and p-hydroxybenzoic acid. They inhibited the activity of both tetrodotoxin-resistant (TTX-r) and tetrodotoxin-sensitive (TTX-s) NaV channels. All the compounds showed low selectivity on NaV channel subtypes. After intraperitoneal injection, three compounds of these compounds exerted analgesic activity in mice. In conclusion, phenolic acids identified in SC demonstrated analgesic activity, facilitating the mechanistic studies of SC in the treatment of neurasthenia. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  5. Characterization of nineteen antimony(III) complexes as potent inhibitors of photosystem II, carbonic anhydrase, and glutathione reductase.

    PubMed

    Karacan, Mehmet Sayım; Rodionova, Margarita V; Tunç, Turgay; Venedik, Kübra Begüm; Mamaş, Serhat; Shitov, Alexandr V; Zharmukhamedov, Sergei K; Klimov, Vyacheslav V; Karacan, Nurcan; Allakhverdiev, Suleyman I

    2016-12-01

    Nineteen antimony(III) complexes were obtained and examined as possible herbicides. Six of these were synthesized for the first time, and their structures were identified using elemental analyses, (1)H-NMR, (13)C-NMR, FTIR, LCMS, magnetic susceptibility, and conductivity measurement techniques. For the nineteen examined antimony(III) complexes their most-stable forms were determined by DFT/B3LYP/LanL2DZ calculation method. These compounds were examined for effects on photosynthetic electron transfer and carbonic anhydrase activity of photosystem II, and glutathione reductase from chloroplast as well were investigated. Our results indicated that all antimony(III) complexes inhibited glutathione reductase activity of chloroplast. A number of these also exhibited good inhibitory efficiency of the photosynthetic and carbonic anhydrase activity of Photosystem II.

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

    PubMed

    Chen, Xi; Liu, Xi-shuang

    2016-03-01

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

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

    PubMed Central

    Chen, Xi; Liu, Xi-shuang

    2016-01-01

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

  8. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway

    SciTech Connect

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan Xian, Shulin; Lu, Yunfei

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. -- Highlights: •Blockage of glycolysis might be a novel way to anticancer. •Both 3-bromopyruvate and sodium citrate could inhibit glycolysis and regulate mitochondrial pathway in cancer cells. •Both 3-bromopyruvate and sodium citrate would be the novel agents on treatment of gastric cancer.

  9. Acanthopanax versus 3-Methyladenine Ameliorates Sodium Taurocholate-Induced Severe Acute Pancreatitis by Inhibiting the Autophagic Pathway in Rats

    PubMed Central

    Zhou, Guoxiong; Liu, Chun; Wei, Ronglong; Zhu, Shunxing; Xu, Yuefen; Wu, Mengjie; Miao, Qing

    2016-01-01

    Objectives. To observe the therapeutic effects of Acanthopanax and 3-methyladenine against severe acute pancreatitis (SAP). Methods. Sodium taurocholate-induced SAP rats were equally randomized into a SAP group, an Acanthopanax group, and a 3-methyladenine group. Serum amylase levels were determined by ELISA; protein and mRNA expression levels of nucleus nuclear factor kappa B (NF-κB) p65, light chain 3II (LC3-II), and Beclin-1 and mRNA expression levels of Class III phosphatidylinositol 3-kinase (PI3K-III) in pancreas tissue were detected by Western blot and quantitative real-time PCR, respectively; mortality and pathological change of the pancreas were observed at 3, 12, and 24 h after operation. Results. There was no significant difference in mortality between SAP group and both treatment groups (P > 0.05). Serum amylase levels, protein, and mRNA expression levels of nucleus NF-κB p65, LC3-II, and Beclin-1 protein, mRNA expression levels of PI3K-III, and pathological score of the pancreas in both treatment groups were significantly lower than those in SAP group at 12 and 24 h after operation (P < 0.05 or 0.01). The number of autophagosomes and autophagolysosomes of pancreatic acinar cells in both treatment groups was smaller than that in SAP group at 12 and 24 h. Conclusions. Acanthopanax and 3-methyladenine had similar therapeutic effects against SAP in rats. The mechanism may be through inhibiting abnormal autophagy activation of pancreatic acinar cells. PMID:28115794

  10. Inhibition of Clostridium botulinum 52A toxicity and protease activity by sodium acid pyrophosphate in media systems.

    PubMed Central

    Wagner, M K; Busta, F F

    1985-01-01

    The effects of two pH levels (5.55 or 5.85) in combination with 0.4% sodium acid pyrophosphate (SAPP), NaH2PO4 X H2O, Na2HPO4 X 7H2O, or NaCl on the growth and toxicity of Clostridium botulinum 52A were studied. Absorbancy measurements at 630 nm, microscopic observations, and the mouse bioassay procedure were used to observe the effects. At pH 5.55 and 5.85 most control cultures exhibited toxicity when cell lysis began. Vegetative cell development was normal (4 micron long; 1 micron wide). SAPP-containing (0.4%) treatment cultures displayed similar growth and lysis but no or delayed (48 h) toxicity. Cells grown in the SAPP treatment culture were longer and wider (6 micron long; 1.5 micron wide) than in most other treatment cultures. Trypsinization of nontoxic supernatants from 0.4% SAPP resulted in toxicity. Addition of 0.4% SAPP to toxic C. botulinum supernatant delayed but did not prevent death of mice. The addition of various levels of SAPP to toxic supernatants resulted in a decrease in zone size with an increase in the level of SAPP (9 mm with 0.4% SAPP to 7 mm with 1.0% SAPP), using a dual substrate protease assay. A decrease in the zone size also occurred with the supernatant from cultures grown in the presence of SAPP and with Bacillus polymyxa protease dilutions containing 0.4% SAPP. Results suggest that the actual production or function of the protease responsible for toxin activation may have been inhibited by the presence of SAPP. PMID:2992374

  11. Inhibition of mast cell-derived histamine secretion by cromolyn sodium treatment decreases biliary hyperplasia in cholestatic rodents.

    PubMed

    Kennedy, Lindsey L; Hargrove, Laura A; Graf, Allyson B; Francis, Taylor C; Hodges, Kyle M; Nguyen, Quy P; Ueno, Yoshi; Greene, John F; Meng, Fanyin; Huynh, Victoria D; Francis, Heather L

    2014-12-01

    Cholangiopathies are characterized by dysregulation of the balance between biliary growth and loss. We have shown that histamine (HA) stimulates biliary growth via autocrine mechanisms. To evaluate the paracrine effects of mast cell (MC) stabilization on biliary proliferation, sham or BDL rats were treated by IP-implanted osmotic pumps filled with saline or cromolyn sodium (24 mg/kg BW/day (inhibits MC histamine release)) for 1 week. Serum, liver blocks and cholangiocytes were collected. Histidine decarboxylase (HDC) expression was measured using real-time PCR in cholangiocytes. Intrahepatic bile duct mass (IBDM) was evaluated by IHC for CK-19. MC number was determined using toluidine blue staining and correlated to IBDM. Proliferation was evaluated by PCNA expression in liver sections and purified cholangiocytes. We assessed apoptosis using real-time PCR and IHC for BAX. Expression of MC stem factor receptor, c-kit, and the proteases chymase and tryptase were measured by real-time PCR. HA levels were measured in serum by EIA. In vitro, MCs and cholangiocytes were treated with 0.1% BSA (basal) or cromolyn (25 μM) for up to 48 h prior to assessing HDC expression, HA levels and chymase and tryptase expression. Supernatants from MCs treated with or without cromolyn were added to cholangiocytes before measuring (i) proliferation by MTT assays, (ii) HDC gene expression by real-time PCR and (iii) HA release by EIA. In vivo, cromolyn treatment decreased BDL-induced: (i) IBDM, MC number, and biliary proliferation; (ii) HDC and MC marker expression; and (iii) HA levels. Cromolyn treatment increased cholangiocyte apoptosis. In vitro, cromolyn decreased HA release and chymase and tryptase expression in MCs but not in cholangiocytes. Cromolyn-treated MC supernatants decreased biliary proliferation and HA release. These studies provide evidence that MC histamine is key to biliary proliferation and may be a therapeutic target for the treatment of cholangiopathies.

  12. Açaí Berries Inhibit Colon Tumorigenesis in Azoxymethane/Dextran Sulfate Sodium-Treated Mice

    PubMed Central

    Choi, Yoon Jin; Choi, Yoon Jeong; Kim, Nayoung; Nam, Ryoung Hee; Lee, Seonmin; Lee, Hye Seung; Lee, Ha-Na; Surh, Young-Joon; Lee, Dong Ho

    2017-01-01

    Background/Aims The aim of this study was to investigate the protective effect of açaí against azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colorectal cancer development. Methods The effect of açaí on tumorigenesis was assessed by evaluating tumor incidence, multiplicity and invasiveness in the mouse colon. The levels of myeloperoxidase (MPO) and proinflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin [IL]-1β, and IL-6) were measured via enzyme-linked immunosorbent assay. Protein levels of cyclooxygenase 2 (COX-2), proliferating cell nuclear antigen (PCNA), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated death promoter (Bad) and cleaved-caspase-3 were assessed by immunoblotting. Results Administration of pellets containing 5% açaí powder reduced the incidences of both colonic adenoma and cancer (adenoma, 23.1% vs 76.9%, respectively, p=0.006; cancer, 15.4% vs 76.9%, respectively, p=0.002). In the açaí-treated mice, the MPO, TNF-α, IL-1β and IL-6 levels in the colon were significantly down-regulated. Açaí inhibited PCNA and Bcl-2 expression and increased Bad and cleaved-caspase-3 expression. In vitro studies demonstrated that açaí treatment reduced lipopolysaccharide-induced expression of TNF-α, IL-1β, IL-6 and COX-2 in murine macrophage RAW 264.7 cells. Conclusions Açaí demonstrated protective effects against AOM/DSS-induced colon carcinogenesis, which suggests that the intake of açaí may be beneficial for the prevention of human colon cancer. PMID:27965474

  13. Baicalin may alleviate inflammatory infiltration in dextran sodium sulfate-induced chronic ulcerative colitis via inhibiting IL-33 expression.

    PubMed

    Zhang, Cheng-Liang; Zhang, Si; He, Wen-Xi; Lu, Jing-Li; Xu, Yan-Jiao; Yang, Jin-Yu; Liu, Dong

    2017-10-01

    To investigate the therapeutic effect of baicalin treatment in chronic ulcerative colitis (UC), and explore the potential anti-inflammation mechanism(s) via IL-33 pathway. UC model were established by giving three cycles of 5-day 2% dextran sodium sulfate (DSS) with two intervals of 14-day recovery in mice, totaling 43days. At the 13th day of the UC modeling, mice received baicalin at doses of 50, 100, or 150mg/kg, respectively. Disease activity index (DAI) assessment as well as HE and PAS staining were performed. Serum levels of TNF-α, IL-1β and IL-6 were determined by ELISA. Myeloperoxidase (MPO) activity and nitric oxide (NO) contents in colon were measured. The expressions of IL-33 and Ly6/G were examined by immunochemistry. And contents of IL-33 protein and NF-κB-related proteins were tested by Western blot. Morphological and histological analyses revealed that baicalin administration had a significant effect on reducing the severity of DSS-induced UC in mice. Besides, baicalin treatment significantly reduced the levels of MPO and NO. Moreover, increased levels of inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, have been identified in damaged colon tissue, which was noticeably reduced by baicalin treatment. Our data demonstrated that protein levels of IL-33 and NF-κB p65 were elevated in colon tissues of chronic UC mice. Baicalin treatment significantly suppressed levels of IL-33 and NF-κB p65, whereas levels of IκB-α were increased. Baicalin treatment effectively alleviated DSS-induced chronic UC, and the protective mechanisms may involve inhibition of IL-33 expression and subsequent NF-κB activation. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. THE CRYSTAL STRUCTURE OF ANTIMONY (III) SULFOBROMIDE, SBSBR,

    DTIC Science & Technology

    ANTIMONY COMPOUNDS, *SULFUR COMPOUNDS, CRYSTAL STRUCTURE , CRYSTAL STRUCTURE , BROMIDES, SYMMETRY(CRYSTALLOGRAPHY), FOURIER ANALYSIS, MOLECULAR STRUCTURE, CRYSTAL LATTICES, CHEMICAL BONDS, X RAY DIFFRACTION.

  15. Resistance mechanisms to arsenicals and antimonials.

    PubMed

    Rosen, B P

    1995-01-01

    Salts and organic derivatives of arsenic and antimony are quite toxic. Living organisms have adapted to this toxicity by the evolution of resistance mechanisms. Both prokaryotic and eukaryotic cells develop resistance when exposed to arsenicals or antimonials. In the case of bacteria resistance is conferred by plasmid-encoded arsenical resistance (ars) operons. The genes and gene products of the ars operon of the clinically-isolated conjugative R-factor R773 have been identified and their mechanism of action elucidated. The operon encodes an ATP-driven pump that extrudes arsenite and antimonite from the cells. The lowering of their intracellular concentration results in resistance. Arsenate resistance results from the action of the plasmid-encoded arsenate reductase that reduces arsenate to arsenite, which is then pumped out of the cell.

  16. Pentoxifylline prevents the meglumine antimonate-induced renal toxicity in rats, but not that induced by the inorganic antimony pentachloride.

    PubMed

    de Moura, Flávio José Dutra; Leal, Pushkin Pires; de Souza Furtado, Rogério; Muniz-Junqueira, Maria Imaculada; Veiga, Joel Paulo Russomano

    2008-01-14

    Tumor necrosis factor-alpha (TNF-alpha) is a mediator of inflammation and has an important role in human and experimental renal diseases. Pentoxifylline (PTX) has been shown to inhibit cytokine synthesis, including TNF-alpha. The aim of the present study was to examine the effect of PTX on meglumine antimonate (Sb(V)) and antimony pentachloride (SbCl(5))-induced renal toxicity in rats. Sixty Wistar rats were divided into six groups according to the treatment employed over the period of 7 days: group I-saline (NaCl 0.9%); group II-PTX plus saline; group III-meglumine antimonate (Sb(V)) plus saline; group IV-meglumine antimonate (Sb(V)) plus PTX; group V-SbCl(5) plus saline; group VI-SbCl(5) with PTX. The animals' urinary concentration ability was evaluated before and after the end of the treatment. Urine and blood osmolality, sodium and creatinine concentration, and urine volume per minute (V) were determined. Creatinine clearance (CrCl), fractional sodium excretion (FE(Na)), and urine to plasma osmolality ratio (U/P osm) were calculated. TNF-alpha concentration in blood was assessed. On the seventh day, the animals were sacrificed and their kidneys were submitted to histological analysis. The meglumine antimonate (Sb(V))-treated animals showed an impaired renal capacity to concentrate urine, with low values of the ratio U/P osm, reduction in CrCl, and an increment in TNF-alpha serum levels. PTX associated with meglumine antimonate (Sb(V)) reduced TNF-alpha serum levels and was effective in preventing renal functional alterations. Rats treated with SbCl(5) showed functional and histopathologic alterations compatible with acute tubular necrosis, and treatment with PTX did not prevent SbCl(5)-induced nephrotoxicity. PTX was effective in preventing renal functional alterations induced by meglumine antimonate (Sb(V)) in rats.

  17. Gas phase antimony/magnesium/oxygen clusters

    SciTech Connect

    Deng, H.T.; Okada, Y.; Foltin, M.; Castleman, A.W. Jr. )

    1994-09-15

    Antimony/magnesium/oxygen clusters are produced by a gas aggregation source, in which a mixture of antimony and magnesium is vaporized and reacted with N[sub 2]O introduced in helium carrier gas. The resulting product distribution is detected by a time-of-flight mass spectrometer following ionization with a KrF excimer laser. Four types of cluster products are observed: Sb[sub x][sup +], Sb[sub x]Mg[sub y]O[sub z][sup +], Sb[sub x]Mg[sub y][sup +], and Mg[sub y]O[sub z][sup +]. The mass spectral intensity distributions display enhanced abundances for Mg[sub 2]O[sup +], Sb[sub 2[minus]4]Mg[sub 3]O[sup +], Sb[sub 1[minus]4]Mg[sub 2]O[sup +], Sb[sub 4]Mg[sup +], Sb[sub 5]Mg[sub 2][sup +], and Sb[sub 6]Mg[sub 2][sup +]. The experimental observation of Mg[sub 2]O[sup +] and Mg[sub 3]O[sup +] shows that the suboxides of group 2 are stable species, consistent with theoretical predictions. The binding abilities of antimony clusters to magnesium and magnesium oxides are found to be dependent on cluster size. When the number of antimony atoms in the clusters is smaller than 6, Sb[sub x]Mg[sub y]O[sub z][sup +] are the main products dominating the mass distribution the mass distribution. On the other hand, when the cluster size of Sb[sub x] is larger than 6, only Sb/Mg alloy clusters are observed. 52 refs., 3 figs., 1 tab.

  18. The heat capacity of solid antimony selenide

    NASA Astrophysics Data System (ADS)

    Pashinkin, A. S.; Malkova, A. S.; Mikhailova, M. S.

    2008-06-01

    The literature data on the heat capacity of solid antimony selenide over the temperature range 53 K- T m were analyzed. The heat capacity of Sb2Se3 was measured from 350 to 600 K on a DSM-2M calorimeter. The experimental data were used to calculate the dependence C p = a + bT + cT -2 and the thermodynamic functions of solid Sb2Se3 over the temperature range 298.15 700 K.

  19. [Removal of Antimony in Wastewater by Electrochemical Hydride Generation and the Recovery of Antimony].

    PubMed

    Chen, Jing-jing; Zhang, Guo-ping; Li, Hai-xia; Fu, Zhi-ping; Ouyang, Xiao-xue; Wu, Qiong

    2015-04-01

    An electrochemical hydride generation method was developed for the removal of antimony in wastewater. Hydrogen was generated in the electrolysis of water. Hydrogen reacted with Sb and formed stibine, which volatilized from the solution. Then, stibine was heated and decomposed to elemental Sb. Based on these, Sb in wastewater could be removed and recovered. The highest removal of Sb (76.1%) was achieved in acidic solution (pH = 4). The formation of stibine was proven to contribute most significantly (66.2%) to the removal of antimony in the solution, while the electro-deposition and adsorption also made a small contribution. In the treatment, Sb(V) must be pre-reduced to Sb(III) prior to the formation of stibine. Lead, graphite and tungsten were employed as the materials for cathode, and lead electrode was found most suitable for the removal of antimony.

  20. High Temperature Interactions of Antimony with Nickel

    SciTech Connect

    Marina, Olga A.; Pederson, Larry R.

    2012-07-01

    In this chapter, the surface and bulk interactions of antimony with the Ni-based anodes in solid oxide fuel cells (SOFC) will be discussed. High fuel flexibility is a significant advantage of SOFCs, allowing the direct use of fossil and bio fuels without a hydrogen separation unit. Synthesis gas derived from coal and biomass consists of a mixture of hydrogen, carbon monoxide, carbon dioxide, and steam, but finite amounts of tars and trace impurities such as S, Se, P, As, Sb, Cd, Pb, Cl, etc, are also always present. While synthesis gas is commonly treated with a series of chemical processes and scrubbers to remove the impurities, complete purification is not economical. Antimony is widely distributed in coals. During coal gasification antimony is volatilized, such that contact with the SOFC anodes and other SOFC parts, e.g., interconnect, current collecting wires, fuel gas supplying tubing, is most likely. This chapter addresses the following topics: high temperature Ni - Sb interactions; alteration phase, Ni3Sb, Ni5Sb2, NiSb, formation; thermochemical modeling; impact of Sb on the electrocatalytic activity of Ni toward the fuel oxidation and the presence of other impurities (sulfur, in particular); converted anode structural instability during long-term SOFC operation; comparison with nickel heterogeneous catalysts.

  1. Comparing polyaluminum chloride and ferric chloride for antimony removal.

    PubMed

    Kang, Meea; Kamei, Tasuku; Magara, Yasumoto

    2003-10-01

    Antimony has been one of the contaminants required to be regulated, however, only limited information has been collected to date regarding antimony removal by polyaluminium chloride (PACl) and ferric chloride (FC). Accordingly, the possible use of coagulation by PACl or FC for antimony removal was investigated. Jar tests were used to determine the effects of solution pH, coagulant dosage, and pre-chlorination on the removal of various antimony species. Although high-efficiency antimony removal by aluminum coagulation has been expected because antimony is similar to arsenic in that both antimony and arsenic are a kind of metalloid in group V of the periodic chart, this study indicated: (1) removal density (arsenic or antimony removed per mg coagulant) for antimony by PACl was about one forty-fifth as low as observed for As(V); (2) although the removal of both Sb(III) and Sb(V) by coagulation with FC was much higher than that of PACl, a high coagulant dose of 10.5mg of FeL(-1) at optimal pH of 5.0 was still not sufficient to meet the standard antimony level of 2 microg as SbL(-1) for drinking water when around 6 microg as SbL(-1) were initially present. Consequently, investigation of a more appropriate treatment process is necessary to develop economical Sb reduction; (3) although previous studies concluded that As(V) is more effectively removed than As(III), this study showed that the removal of Sb(III) by coagulation with FC was much more pronounced than that of Sb(V); (4) oxidation of Sb(III) with chlorine decreased the ability of FC to remove antimony. Accordingly, natural water containing Sb(III) under anoxic condition should be coagulated without pre-oxidation.

  2. Methods of analysis by the U.S. Geological Survey National Water Quality Laboratory; determination of antimony by automated-hydride atomic absorption spectrophotometry

    USGS Publications Warehouse

    Brown, G.E.; McLain, B.J.

    1994-01-01

    The analysis of natural-water samples for antimony by automated-hydride atomic absorption spectrophotometry is described. Samples are prepared for analysis by addition of potassium and hydrochloric acid followed by an autoclave digestion. After the digestion, potassium iodide and sodium borohydride are added automatically. Antimony hydride (stibine) gas is generated, then swept into a heated quartz cell for determination of antimony by atomic absorption spectrophotometry. Precision and accuracy data are presented. Results obtained on standard reference water samples agree with means established by interlaboratory studies. Spike recoveries for actual samples range from 90 to 114 percent. Replicate analyses of water samples of varying matrices give relative standard deviations from 3 to 10 percent.

  3. A chewing gum containing 7.5% sodium hexametaphosphate inhibits stain deposition compared with a placebo chewing gum.

    PubMed

    Biesbrock, Aaron R; Walters, Patricia; Bartizek, Robert D

    2004-04-01

    The 2-period, randomized, double-blind, placebo-controlled, crossover study compared the stain-prevention and stain-removal benefit of a chewing gum containing 7.5% sodium hexametaphosphate (measured by digital image analysis) with a placebo chewing gum. The results of this study support that sodium hexametaphosphate delivered from a chewing gum prevents dental stain formation and facilitates stain removal, which leads to a perceptible whitening benefit. The long-term clinical benefits of sodium hexametaphosphate delivered from chewing gum have not been reported in the literature.

  4. Determination of antimony in concentrates, ores and non-ferrous materials by atomic-absorption spectrophotometry after iron-lanthanum collection, or by the iodide method after further xanthate extraction.

    PubMed

    Donaldson, E M

    1979-11-01

    Methods for determining trace and moderate amounts of antimony in copper, nickel, molybdenum, lead and zinc concentrates and in ores are described. Following sample decomposition, antimony is oxidized to antimony(V) with aqua regia, then reduced to antimony(III) with sodium metabisulphite in 6M hydrochloric acid medium and separated from most of the matrix elements by co-precipitation with hydrous ferric and lanthanum oxides. Antimony (>/= 100 mug/g) can subsequently be determined by atomic-absorption spectrophotometry, at 217.6 nm after dissolution of the precipitate in 3M hydrochloric acid. Alternatively, for the determination of antimony at levels of 1 mug/g or more, the precipitate is dissolved in 5M hydrochloric acid containing stannous chloride as a reluctant for iron(III) and thiourea as a complexing agent for copper. Then tin is complexed with hydrofluoric acid, and antimony is separated from iron, tin, lead and other co-precipitated elements, including lanthanum, by chloroform extraction of its xanthate. It is then determined spectrophotometrically, at 331 or 425 nm as the iodide. Interference from co-extracted bismuth is eliminated by washing the extract with hydrochloric acid of the same acid concentration as the medium used for extraction. Interference from co-extracted molybdenum, which causes high results at 331 nm, is avoided by measuring the absorbance at 425 nm. The proposed methods are also applicable to high-purity copper metal and copper- and lead-base alloys. In the spectrophotometric iodide method, the importance of the preliminary oxidation of all of the antimony to antimony(V), to avoid the formation of an unreactive species, is shown.

  5. Study of the synergistic effect of 2-methoxy-4-formylphenol and sodium molybdenum oxide on the corrosion inhibition of 3CR12 ferritic steel in dilute sulphuric acid

    NASA Astrophysics Data System (ADS)

    Loto, Roland Tolulope

    The synergistic effect of the corrosion inhibition properties of 2-methoxy-4-formylphenol and sodium molybdenum oxide on the electrochemical property of 3CR12 ferritic stainless steel in 2M H2SO4 acid solution was assessed through coupon analysis, potentiodynamic polarization technique, IR spectroscopy and micro-analytical technique. Experimental data showed the combined admixture effectively inhibited the steel corrosion at the concentrations analyzed with a maximum inhibition efficiency of 94.47% and 89.71% from coupon analysis and potentiodynamic polarization due to the electrochemical action and inhibition of the steel by the ionized molecules of the inhibiting compound which influenced the mechanism of the redox reactions responsible to corrosion and surface deterioration. Results from corrosion thermodynamic calculations showed chemisorption adsorption mechanism. Infrared spectroscopic images exposed the functional groups of the molecules involved for the corrosion inhibition reaction. Micro-analytical images showed sharp contrast in surface morphology between the inhibited and corroded test specimens under study. Cracks, intergranular and pitting corrosion in addition to severe surface deterioration was observed in the uninhibited samples. Inhibitor adsorption fits the Langmuir isotherm model.

  6. In Vitro Inhibition of Cytopathic Effect of Influenza Virus and Human Immunodeficiency Virus by Bamboo Leaf Extract Solution and Sodium Copper Chlorophyllin

    PubMed Central

    Ito, Akiko; Tsuneki, Akeno; Yoshida, Yu; Ryoke, Kazuo; Kaidoh, Toshiyuki; Kageyama, Seiji

    2016-01-01

    Background Although the link between oral and oropharyngeal health status and susceptibility to infection has long been recognized, there is a limit to the selection of antiseptics for oral care. Methods Madin-Darby canine kidney (MDCK) cells were exposed to influenza virus and cultured in the presence or absence of test reagents: bamboo leaf extract solution and sodium copper chrolophyllin. MDCK cells were pre-incubated with the reagents to assess the inhibitory activity at adsorption (viral attachment). Similarly, anti-HIV activity and the inhibitory mechanism at adsorption were assessed by MT-2 cell culture system. Mixture of HIV and bamboo leaf extract solution was fixed and examined by transmission electron microscopy. Results The 50% inhibitory concentration (IC50) of bamboo leaf extract solution against influenza virus and the 50% cytotoxic concentration (CC50) in MDCK cells of the solution lay between 0.0313–0.0625% and 0.5–1.0%. The solution inhibited the influenza virus adsorption at the concentration of 0.5% (P < 0.05). The values of IC50 and CC50 of sodium copper chlorophyllin lay between 50–100 µM and 200–400 µM, respectively. This inhibited the virus adsorption at 200 µM (P < 0.05). The bamboo leaf extract solution showed values of IC50 against HIV and CC50 in MT-2 cells at around 0.0313% and between 0.25–0.5%, respectively. This solution inhibited HIV adsorption at 1.25% (P < 0.05). The IC50 and CC50 of sodium copper chlorophyllin lay between 50–100 µM and 200–400 µM, respectively. Sodium copper chlorophyllin inhibited HIV adsorption at 2.5 mM (P < 0.05). HIV particles survived after the exposure to 0.5% bamboo leaf extract solution. Conclusion Sodium copper chlorophyllin exerted antiviral activities against influenza virus and HIV as the major ingredient of bamboo leaf extract solution by blocking adsorption. This mechanism of action is different completely from the one of povidone-iodine. PMID:27046952

  7. In Vitro Inhibition of Cytopathic Effect of Influenza Virus and Human Immunodeficiency Virus by Bamboo Leaf Extract Solution and Sodium Copper Chlorophyllin.

    PubMed

    Ito, Akiko; Tsuneki, Akeno; Yoshida, Yu; Ryoke, Kazuo; Kaidoh, Toshiyuki; Kageyama, Seiji

    2016-03-01

    Although the link between oral and oropharyngeal health status and susceptibility to infection has long been recognized, there is a limit to the selection of antiseptics for oral care. Madin-Darby canine kidney (MDCK) cells were exposed to influenza virus and cultured in the presence or absence of test reagents: bamboo leaf extract solution and sodium copper chrolophyllin. MDCK cells were pre-incubated with the reagents to assess the inhibitory activity at adsorption (viral attachment). Similarly, anti-HIV activity and the inhibitory mechanism at adsorption were assessed by MT-2 cell culture system. Mixture of HIV and bamboo leaf extract solution was fixed and examined by transmission electron microscopy. The 50% inhibitory concentration (IC50) of bamboo leaf extract solution against influenza virus and the 50% cytotoxic concentration (CC50) in MDCK cells of the solution lay between 0.0313-0.0625% and 0.5-1.0%. The solution inhibited the influenza virus adsorption at the concentration of 0.5% (P < 0.05). The values of IC50 and CC50 of sodium copper chlorophyllin lay between 50-100 µM and 200-400 µM, respectively. This inhibited the virus adsorption at 200 µM (P < 0.05). The bamboo leaf extract solution showed values of IC50 against HIV and CC50 in MT-2 cells at around 0.0313% and between 0.25-0.5%, respectively. This solution inhibited HIV adsorption at 1.25% (P < 0.05). The IC50 and CC50 of sodium copper chlorophyllin lay between 50-100 µM and 200-400 µM, respectively. Sodium copper chlorophyllin inhibited HIV adsorption at 2.5 mM (P < 0.05). HIV particles survived after the exposure to 0.5% bamboo leaf extract solution. Sodium copper chlorophyllin exerted antiviral activities against influenza virus and HIV as the major ingredient of bamboo leaf extract solution by blocking adsorption. This mechanism of action is different completely from the one of povidone-iodine.

  8. Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

    SciTech Connect

    Saldanha, Sabita N.; Kala, Rishabh; Tollefsbol, Trygve O.

    2014-05-15

    Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer (CRC) cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with the combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in CRC cells. - Highlights: • EGCG and NaB as a combination inhibits colorectal cancer cell proliferation. • The combination treatment induces DNA damage, G2/M and G1 arrest and apoptosis. • Survivin is effectively down-regulated by the combination treatment. • p21 and p53 expressions are induced by the combination treatment. • Epigenetic proteins DNMT1 and HDAC1 are

  9. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis.

    PubMed

    Perry, Meghan R; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H

    2013-12-03

    The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg · mL(-1) Pentostam compared with the control passage group (38.5 μg · mL(-1)) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is.

  10. Chronic exposure to arsenic in drinking water can lead to resistance to antimonial drugs in a mouse model of visceral leishmaniasis

    PubMed Central

    Perry, Meghan R.; Wyllie, Susan; Raab, Andrea; Feldmann, Joerg; Fairlamb, Alan H.

    2013-01-01

    The Indian subcontinent is the only region where arsenic contamination of drinking water coexists with widespread resistance to antimonial drugs that are used to treat the parasitic disease visceral leishmaniasis. We have previously proposed that selection for parasite resistance within visceral leishmaniasis patients who have been exposed to trivalent arsenic results in cross-resistance to the related metalloid antimony, present in the pentavalent state as a complex in drugs such as sodium stibogluconate (Pentostam) and meglumine antimonate (Glucantime). To test this hypothesis, Leishmania donovani was serially passaged in mice exposed to arsenic in drinking water at environmentally relevant levels (10 or 100 ppm). Arsenic accumulation in organs and other tissues was proportional to the level of exposure and similar to that previously reported in human liver biopsies. After five monthly passages in mice exposed to arsenic, isolated parasites were found to be completely refractory to 500 μg⋅mL−1 Pentostam compared with the control passage group (38.5 μg⋅mL−1) cultured in vitro in mouse peritoneal macrophages. Reassessment of resistant parasites following further passage for 4 mo in mice without arsenic exposure showed that resistance was stable. Treatment of infected mice with Pentostam confirmed that resistance observed in vitro also occurred in vivo. We conclude that arsenic contamination may have played a significant role in the development of Leishmania antimonial resistance in Bihar because inadequate treatment with antimonial drugs is not exclusive to India, whereas widespread antimonial resistance is. PMID:24167266

  11. The exposure to and health effects of antimony.

    PubMed

    Cooper, Ross G; Harrison, Adrian P

    2009-04-01

    This minireview describes the health effects of antimony exposure in the workplace and the environment. To collate information on the consequences of occupational and environmental exposure to antimony on physiological function and well-being. The criteria used in the current minireview for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability and Health. Articles were classified from an acute and chronic exposure and toxicity thrust. The proportion of utilised and non-utilised articles was tabulated. Antimony toxicity is dependent on the exposure dose, duration, route (breathing, eating, drinking, or skin contact), other chemical exposures, age, sex, nutritional status, family traits, life style, and state of health. Chronic exposure to antimony in the air at levels of 9 mg/m(3) may exacerbate irritation of the eyes, skin, and lungs. Long-term inhalation of antimony can potentiate pneumoconiosis, altered electrocardiograms, stomach pain, diarrhea, vomiting, and stomach ulcers, results which were confirmed in laboratory animals. Although there were investigations of the effect of antimony in sudden infant death syndrome, current findings suggest no link. Antimony trioxide exposure is predominant in smelters. Mining and exposure via glass working, soldering, and brazing are also important. Antimony has some useful but undoubtedly harmful effects on health and well-being and measures need to be taken to prevent hazardous exposure of the like. Its biological monitoring in the workplace is essential.

  12. 21 CFR 862.3110 - Antimony test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Antimony test system. 862.3110 Section 862.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... antimony, a heavy metal, in urine, blood, vomitus, and stomach contents. Measurements obtained by this...

  13. 21 CFR 862.3110 - Antimony test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimony test system. 862.3110 Section 862.3110 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... antimony, a heavy metal, in urine, blood, vomitus, and stomach contents. Measurements obtained by this...

  14. The exposure to and health effects of antimony

    PubMed Central

    Cooper, Ross G.; Harrison, Adrian P.

    2009-01-01

    Context: This minireview describes the health effects of antimony exposure in the workplace and the environment. Aim: To collate information on the consequences of occupational and environmental exposure to antimony on physiological function and well-being. Methods: The criteria used in the current minireview for selecting articles were adopted from proposed criteria in The International Classification of Functioning, Disability and Health. Articles were classified from an acute and chronic exposure and toxicity thrust. Results: The proportion of utilised and non-utilised articles was tabulated. Antimony toxicity is dependent on the exposure dose, duration, route (breathing, eating, drinking, or skin contact), other chemical exposures, age, sex, nutritional status, family traits, life style, and state of health. Chronic exposure to antimony in the air at levels of 9 mg/m3 may exacerbate irritation of the eyes, skin, and lungs. Long-term inhalation of antimony can potentiate pneumoconiosis, altered electrocardiograms, stomach pain, diarrhea, vomiting, and stomach ulcers, results which were confirmed in laboratory animals. Although there were investigations of the effect of antimony in sudden infant death syndrome, current findings suggest no link. Antimony trioxide exposure is predominant in smelters. Mining and exposure via glass working, soldering, and brazing are also important. Conclusion: Antimony has some useful but undoubtedly harmful effects on health and well-being and measures need to be taken to prevent hazardous exposure of the like. Its biological monitoring in the workplace is essential. PMID:20165605

  15. Removal of antimony from copper by injection of soda ash

    NASA Astrophysics Data System (ADS)

    Stapurewicz, Tadeusz T.; Themelis, Nickolas J.

    1990-12-01

    The removal of Sb from molten copper is of importance in the development of processes which can smelt copper concentrates directly into copper in a single furnace. A promising method is injection of oxygen and sodium carbonate in a modified anode furnace. This study encompassed a thermodynamic analysis of the impurity removal reactions and an experimental investigation of antimony removal from molten copper in a 15 kW induction furnace. The results showed that the reaction was controlled by diffusion of Sb in the metal phase. The reaction between metal and injected flux can be divided into two subprocesses-. (1) “transitory contact” reaction to the injected flux particles as they rise through the melt and (2) “permanent contact” reaction across the interface between the metal bath and the supernatant slag layer. On the basis of the experimental work, the overall volumetric mass transfer coefficient (cm3/s) at 1473 K was expressed in terms of the two subprocesses as follows: (k d A) ov = (k d A) pc + (k d A) tc = 1.25Q{g/0.29} + 0.28 (H Q f ) where Q g is the injection gas flow rate in normal liters per minute, H is the depth of injection in centimeters, and Q f the rate of flux injection in grams per second.

  16. Food additives such as sodium sulphite, sodium benzoate and curcumin inhibit leptin release in lipopolysaccharide-treated murine adipocytes in vitro.

    PubMed

    Ciardi, Christian; Jenny, Marcel; Tschoner, Alexander; Ueberall, Florian; Patsch, Josef; Pedrini, Michael; Ebenbichler, Christoph; Fuchs, Dietmar

    2012-03-01

    Obesity leads to the activation of pro-inflammatory pathways, resulting in a state of low-grade inflammation. Recently, several studies have shown that the exposure to lipopolysaccharide (LPS) could initiate and maintain a chronic state of low-grade inflammation in obese people. As the daily intake of food additives has increased substantially, the aim of the present study was to investigate a potential influence of food additives on the release of leptin, IL-6 and nitrite in the presence of LPS in murine adipocytes. Leptin, IL-6 and nitrite concentrations were analysed in the supernatants of murine 3T3-L1 adipocytes after co-incubation with LPS and the food preservatives, sodium sulphite (SS), sodium benzoate (SB) and the spice and colourant, curcumin, for 24 h. In addition, the kinetics of leptin secretion was analysed. A significant and dose-dependent decrease in leptin was observed after incubating the cells with SB and curcumin for 12 and 24 h, whereas SS decreased leptin concentrations after 24 h of treatment. Moreover, SS increased, while curcumin decreased LPS-stimulated secretion of IL-6, whereas SB had no such effect. None of the compounds that were investigated influenced nitrite production. The food additives SS, SB and curcumin affect the leptin release after co-incubation with LPS from cultured adipocytes in a dose- and time-dependent manner. Decreased leptin release during the consumption of nutrition-derived food additives could decrease the amount of circulating leptin to which the central nervous system is exposed and may therefore contribute to an obesogenic environment.

  17. Antimony Uptake Systems in the Protozoan Parasite Leishmania and Accumulation Differences in Antimony-Resistant Parasites

    PubMed Central

    Brochu, Christian; Wang, Jingyu; Roy, Gaétan; Messier, Nadine; Wang, Xiao-Yan; Saravia, Nancy G.; Ouellette, Marc

    2003-01-01

    The first line drug against leishmaniasis consists of pentavalent antimony [Sb(V)], but there is general belief that the active form of the metal is the trivalent form [Sb(III)]. In this study, we have quantified the accumulation of Sb(V) and Sb(III) in Leishmania by using inductively coupled plasma mass spectrometry. The accumulation was studied in three Leishmania species at various life stages, sensitive or resistant to antimony. Both Sb(III) and Sb(V) are accumulated in promastigote and amastigote parasites, but through competition experiments with arsenite, we found that the routes of entry of Sb(V) and Sb(III) are likely to differ in Leishmania. The level of accumulation of either Sb(III) or Sb(V), however, was not correlated with the susceptibility of wild-type Leishmania cells to antimony. This suggests that other factors may also be implicated in the mode of action of the drugs. In contrast to metal susceptibility, resistance to Sb(III) correlated well with decreased antimony accumulation. This phenotype was energy dependent and highlights the importance of transport systems in drug resistance of this protozoan parasite. PMID:14506011

  18. 40 CFR 440.90 - Applicability; description of the antimony ore subcategory.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... antimony ore subcategory. 440.90 Section 440.90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Antimony Ore Subcategory § 440.90 Applicability; description of the antimony ore subcategory. The provisions of this subpart I are applicable to discharges from (a) mines that produce antimony ore and (b...

  19. 40 CFR 440.90 - Applicability; description of the antimony ore subcategory.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... antimony ore subcategory. 440.90 Section 440.90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Antimony Ore Subcategory § 440.90 Applicability; description of the antimony ore subcategory. The provisions of this subpart I are applicable to discharges from (a) mines that produce antimony ore and (b...

  20. 40 CFR 440.90 - Applicability; description of the antimony ore subcategory.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... antimony ore subcategory. 440.90 Section 440.90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Antimony Ore Subcategory § 440.90 Applicability; description of the antimony ore subcategory. The provisions of this subpart I are applicable to discharges from (a) mines that produce antimony ore and (b...

  1. Caffeic acid phenethyl ester: Inhibition of metastatic cell behaviours via voltage-gated sodium channel in human breast cancer in vitro.

    PubMed

    Fraser, Scott P; Hemsley, Faye; Djamgoz, Mustafa B A

    2016-02-01

    Caffeic acid phenethyl ester, derived from natural propolis, has been reported to have anti-cancer properties. Voltage-gated sodium channels are upregulated in many cancers where they promote metastatic cell behaviours, including invasiveness. We found that micromolar concentrations of caffeic acid phenethyl ester blocked voltage-gated sodium channel activity in several invasive cell lines from different cancers, including breast (MDA-MB-231 and MDA-MB-468), colon (SW620) and non-small cell lung cancer (H460). In the MDA-MB-231 cell line, which was adopted as a 'model', long-term (48 h) treatment with 18 μM caffeic acid phenethyl ester reduced the peak current density by 91% and shifted steady-state inactivation to more hyperpolarized potentials and slowed recovery from inactivation. The effects of long-term treatment were also dose-dependent, 1 μM caffeic acid phenethyl ester reducing current density by only 65%. The effects of caffeic acid phenethyl ester on metastatic cell behaviours were tested on the MDA-MB-231 cell line at a working concentration (1 μM) that did not affect proliferative activity. Lateral motility and Matrigel invasion were reduced by up to 14% and 51%, respectively. Co-treatment of caffeic acid phenethyl ester with tetrodotoxin suggested that the voltage-gated sodium channel inhibition played a significant intermediary role in these effects. We conclude, first, that caffeic acid phenethyl ester does possess anti-metastatic properties. Second, the voltage-gated sodium channels, commonly expressed in strongly metastatic cancers, are a novel target for caffeic acid phenethyl ester. Third, more generally, ion channel inhibition can be a significant mode of action of nutraceutical compounds. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A Telomeric Cluster of Antimony Resistance Genes on Chromosome 34 of Leishmania infantum

    PubMed Central

    Tejera Nevado, Paloma; Bifeld, Eugenia; Höhn, Katharina

    2016-01-01

    The mechanisms underlying the drug resistance of Leishmania spp. are manifold and not completely identified. Apart from the highly conserved multidrug resistance gene family known from higher eukaryotes, Leishmania spp. also possess genus-specific resistance marker genes. One of them, ARM58, was first identified in Leishmania braziliensis using a functional cloning approach, and its domain structure was characterized in L. infantum. Here we report that L. infantum ARM58 is part of a gene cluster at the telomeric end of chromosome 34 also comprising the neighboring genes ARM56 and HSP23. We show that overexpression of all three genes can confer antimony resistance to intracellular amastigotes. Upon overexpression in L. donovani, ARM58 and ARM56 are secreted via exosomes, suggesting a scavenger/secretion mechanism of action. Using a combination of functional cloning and next-generation sequencing, we found that the gene cluster was selected only under antimonyl tartrate challenge and weakly under Cu2+ challenge but not under sodium arsenite, Cd2+, or miltefosine challenge. The selective advantage is less pronounced in intracellular amastigotes treated with the sodium stibogluconate, possibly due to the known macrophage-stimulatory activity of this drug, against which these resistance markers may not be active. Our data point to the specificity of these three genes for antimony resistance. PMID:27324767

  3. A Telomeric Cluster of Antimony Resistance Genes on Chromosome 34 of Leishmania infantum.

    PubMed

    Tejera Nevado, Paloma; Bifeld, Eugenia; Höhn, Katharina; Clos, Joachim

    2016-09-01

    The mechanisms underlying the drug resistance of Leishmania spp. are manifold and not completely identified. Apart from the highly conserved multidrug resistance gene family known from higher eukaryotes, Leishmania spp. also possess genus-specific resistance marker genes. One of them, ARM58, was first identified in Leishmania braziliensis using a functional cloning approach, and its domain structure was characterized in L. infantum Here we report that L. infantum ARM58 is part of a gene cluster at the telomeric end of chromosome 34 also comprising the neighboring genes ARM56 and HSP23. We show that overexpression of all three genes can confer antimony resistance to intracellular amastigotes. Upon overexpression in L. donovani, ARM58 and ARM56 are secreted via exosomes, suggesting a scavenger/secretion mechanism of action. Using a combination of functional cloning and next-generation sequencing, we found that the gene cluster was selected only under antimonyl tartrate challenge and weakly under Cu(2+) challenge but not under sodium arsenite, Cd(2+), or miltefosine challenge. The selective advantage is less pronounced in intracellular amastigotes treated with the sodium stibogluconate, possibly due to the known macrophage-stimulatory activity of this drug, against which these resistance markers may not be active. Our data point to the specificity of these three genes for antimony resistance. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  4. The partial purification of sodium-plus-potassium ion-dependent adenosine triphosphatase from the gills of Anguilla anguilla and its inhibition by orthovanadate.

    PubMed Central

    Bell, M V; Sargent, J R

    1979-01-01

    1. (Na+ +K+)-dependent ATPase was partially purified from eel gills by a procedure in which the microsomal fraction of crude preparations of chloride cells was selectively extracted with sodium dodecyl sulphate. 2. The microsomal specific activity was increased 2-fold during optimal treatment with detergent. 3. The final preparation (56% pure) had a specific activity of 341 mumol of ATP hydrolysed/h per mg of protein and a turnover number of 3560 min-1. The number of ouabain-binding sties equalled the number of sites phosphorylated by ATP. 4. Both sodium orthovanadate and ouabain inhibited the purified preparation more than the microsomal fraction, vanadate being more effective on an equimolar basis than ouabain. 5. Inhibition by orthovanadate was not enhanced at 28 mM-as compared with 1mM-MgCl2 and was not reversed by beta-adrenergic agonists (cf. Josephson & Cantley (1977) Biochemistry 16, 4572--4578). 6. Of various other metallic oxyanions tested only niobate proved an effective inhibitor of the enzyme although this anion was less effective than orthovanadate. 7. Orthovanadate partially inhibited phosphorylation of the enzyme by ATP in the presence of 28 mM-MgCl2. PMID:39542

  5. The partial purification of sodium-plus-potassium ion-dependent adenosine triphosphatase from the gills of Anguilla anguilla and its inhibition by orthovanadate.

    PubMed

    Bell, M V; Sargent, J R

    1979-05-01

    1. (Na+ +K+)-dependent ATPase was partially purified from eel gills by a procedure in which the microsomal fraction of crude preparations of chloride cells was selectively extracted with sodium dodecyl sulphate. 2. The microsomal specific activity was increased 2-fold during optimal treatment with detergent. 3. The final preparation (56% pure) had a specific activity of 341 mumol of ATP hydrolysed/h per mg of protein and a turnover number of 3560 min-1. The number of ouabain-binding sties equalled the number of sites phosphorylated by ATP. 4. Both sodium orthovanadate and ouabain inhibited the purified preparation more than the microsomal fraction, vanadate being more effective on an equimolar basis than ouabain. 5. Inhibition by orthovanadate was not enhanced at 28 mM-as compared with 1mM-MgCl2 and was not reversed by beta-adrenergic agonists (cf. Josephson & Cantley (1977) Biochemistry 16, 4572--4578). 6. Of various other metallic oxyanions tested only niobate proved an effective inhibitor of the enzyme although this anion was less effective than orthovanadate. 7. Orthovanadate partially inhibited phosphorylation of the enzyme by ATP in the presence of 28 mM-MgCl2.

  6. Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs

    PubMed Central

    Franco, Antonia MR; Grafova, Iryna; Soares, Fabiane V; Gentile, Gennaro; Wyrepkowski, Claudia DC; Bolson, Marcos A; Sargentini, Ézio; Carfagna, Cosimo; Leskelä, Markku; Grafov, Andriy

    2016-01-01

    Background Coordination compounds of pentavalent antimony have been, and remain, the first-line drugs in leishmaniasis treatment for >70 years. Molecular forms of Sb (V) complexes are commercialized as sodium stibogluconate (Pentostam®) and meglumine antimoniate (MA) (Glucantime®). Ever-increasing drug resistance in the parasites limits the use of antimonials, due to the low drug concentrations being administered against high parasitic counts. Sb5+ toxicity provokes severe side effects during treatment. To enhance therapeutic potency and to increase Sb (V) concentration within the target cells, we decided to try a new active substance form, a hydrosol of Sb2O5·nH2O nanoparticles (NPs), instead of molecular drugs. Methodology/principal findings Sb2O5·nH2O NPs were synthesized by controlled SbCl5 hydrolysis in a great excess of water. Sb2O5·nH2O phase formation was confirmed by X-ray diffraction. The surface of Sb (V) NPs was treated with ligands with a high affinity for target cell membrane receptors. The mean particle size determined by dynamic light scattering and transmission electron microscopy was ~35–45 nm. In vitro tests demonstrated a 2.5–3 times higher antiparasitic activity of Sb (V) nanohybrid hydrosols, when compared to MA solution. A similar comparison for in vivo treatment of experimental cutaneous leishmaniasis with Sb5+ nanohybrids showed a 1.75–1.85 times more effective decrease in the lesions. Microimages of tissue fragments confirmed the presence of NPs inside the cytoplasm of infected macrophages. Conclusion/significance Sb2O5·nH2O hydrosols are proposed as a new form of treatment for cutaneous leishmaniasis caused by Leishmania amazonensis. The NPs penetrate directly into the affected cells, creating a high local concentration of the drug, a precondition to overcoming the parasite resistance to molecular forms of pentavalent antimonials. The nanohybrids are more effective at a lower dose, when compared to MA, the molecular drug. Our

  7. Nanoscaled hydrated antimony (V) oxide as a new approach to first-line antileishmanial drugs.

    PubMed

    Franco, Antonia Mr; Grafova, Iryna; Soares, Fabiane V; Gentile, Gennaro; Wyrepkowski, Claudia Dc; Bolson, Marcos A; Sargentini, Ézio; Carfagna, Cosimo; Leskelä, Markku; Grafov, Andriy

    Coordination compounds of pentavalent antimony have been, and remain, the first-line drugs in leishmaniasis treatment for >70 years. Molecular forms of Sb (V) complexes are commercialized as sodium stibogluconate (Pentostam(®)) and meglumine antimoniate (MA) (Glucantime(®)). Ever-increasing drug resistance in the parasites limits the use of antimonials, due to the low drug concentrations being administered against high parasitic counts. Sb(5+) toxicity provokes severe side effects during treatment. To enhance therapeutic potency and to increase Sb (V) concentration within the target cells, we decided to try a new active substance form, a hydrosol of Sb2O5·nH2O nanoparticles (NPs), instead of molecular drugs. Sb2O5·nH2O NPs were synthesized by controlled SbCl5 hydrolysis in a great excess of water. Sb2O5·nH2O phase formation was confirmed by X-ray diffraction. The surface of Sb (V) NPs was treated with ligands with a high affinity for target cell membrane receptors. The mean particle size determined by dynamic light scattering and transmission electron microscopy was ~35-45 nm. In vitro tests demonstrated a 2.5-3 times higher antiparasitic activity of Sb (V) nanohybrid hydrosols, when compared to MA solution. A similar comparison for in vivo treatment of experimental cutaneous leishmaniasis with Sb(5+) nanohybrids showed a 1.75-1.85 times more effective decrease in the lesions. Microimages of tissue fragments confirmed the presence of NPs inside the cytoplasm of infected macrophages. Sb2O5·nH2O hydrosols are proposed as a new form of treatment for cutaneous leishmaniasis caused by Leishmania amazonensis. The NPs penetrate directly into the affected cells, creating a high local concentration of the drug, a precondition to overcoming the parasite resistance to molecular forms of pentavalent antimonials. The nanohybrids are more effective at a lower dose, when compared to MA, the molecular drug. Our data suggest that the new form of treatment has the potential to

  8. Antimony diffusion in CdTe

    DOE PAGES

    Colegrove, Eric; Harvey, Steven P.; Yang, Ji -Hui; ...

    2017-02-08

    Group V dopants may be used for next-generation high-voltage cadmium telluride (CdTe) solar photovoltaics, but fundamental defect energetics and kinetics need to be understood. Here, antimony (Sb) diffusion is studied in single-crystal and polycrystalline CdTe under Cd-rich conditions. Diffusion profiles are determined by dynamic secondary ion mass spectroscopy and analyzed with analytical bulk and grain-boundary diffusion models. Slow bulk and fast grain-boundary diffusion are found. Density functional theory is used to understand formation energy and mechanisms. Lastly, the theory and experimental results create new understanding of group V defect kinetics in CdTe.

  9. Undercooling and crystallization behaviour of antimony droplets

    NASA Technical Reports Server (NTRS)

    Graves, J. A.; Perepezko, J. H.

    1986-01-01

    The droplet emulsion technique is presently used to examine the undercooling and crystallization behavior of pure antimony. Control of droplet size and applied cooling rate allowed maximum undercooling to be extended from 0.08 to 0.23 T(m). A droplet coating was produced by means of emulsification which appears to furnish a favorable crystallographic matching for effective nucleation catalysis of a metastable simple cubic structure. Thermal analysis shows the melting temperature of the single cubic phase to be about 625 C.

  10. Nitric oxide synthase (NOS) inhibition for one week improves renal sodium and water excretion in cirrhotic rats with ascites.

    PubMed Central

    Martin, P Y; Ohara, M; Gines, P; Xu, D L; St John, J; Niederberger, M; Schrier, R W

    1998-01-01

    Normalization of the increased vascular nitric oxide (NO) generation with low doses of NG-nitro-L-arginine methyl ester (L-NAME) corrects the hemodynamic abnormalities of cirrhotic rats with ascites. We have undertaken this study to investigate the effect of the normalization of vascular NO production, as estimated by aortic cyclic guanosine monophosphate (cGMP) concentration and endothelial nitric oxide synthase (eNOS) protein expression in the aorta and mesenteric artery, on sodium and water excretion. Rats with carbon tetrachloride-induced cirrhosis and ascites were investigated using balance studies. The cirrhotic rats were separated into two groups, one receiving 0.5 mg/kg per day of L-NAME (CIR-NAME) during 7 d, whereas the other group (CIR) was administrated the same volume of vehicle. Two other groups of rats were used as controls, one group treated with L-NAME and another group receiving the same volume of vehicle. Sodium and water excretion was measured on days 0 and 7. On day 8, blood samples were collected for electrolyte and hormone measurements, and aorta and mesenteric arteries were harvested for cGMP determination and nitric oxide synthase (NOS) immunoblotting. Aortic cGMP and eNOS protein expression in the aorta and mesenteric artery were increased in CIR as compared with CIR-NAME. Both cirrhotic groups had a similar decrease in sodium excretion on day 0 (0.7 versus 0.6 mmol per day, NS) and a positive sodium balance (+0.9 versus +1.2 mmol per day, NS). On day 7, CIR-NAME rats had an increase in sodium excretion as compared with the CIR rats (sodium excretion: 2.4 versus 0.7 mmol per day, P < 0.001) and a negative sodium balance (-0.5 versus +0.8 mmol per day, P < 0.001). The excretion of a water load was also increased after L-NAME administration (from 28+/-5% to 65+/-7, P < 0.05). Plasma renin activity, aldosterone and arginine vasopressin were also significantly decreased in the CIR-NAME, as compared with the CIR rats. The results thus indicate

  11. 3-Bromopyruvate and sodium citrate induce apoptosis in human gastric cancer cell line MGC-803 by inhibiting glycolysis and promoting mitochondria-regulated apoptosis pathway.

    PubMed

    Guo, Xingyu; Zhang, Xiaodong; Wang, Tingan; Xian, Shulin; Lu, Yunfei

    2016-06-17

    Cancer cells are mainly dependent on glycolysis to generate adenosine triphosphate (ATP) and intermediates required for cell growth and proliferation. Thus, inhibition of glycolysis might be of therapeutic value in antitumor treatment. Our previously studies had found that both 3-bromopyruvate (BP) and sodium citrate (SCT) can inhibit tumor growth and proliferation in vitro and in vivo. However, the mechanism involved in the BP and SCT mediated antitumor activity is not entirely clear. In this work, it is demonstrated that BP inhibits the enzyme hexokinase (HK) activity and SCT suppresses the phosphofructokinase (PFK) activity respectively, both the two agents decrease viability, ATP generation and lactate content in the human gastric cancer cell line MGC-803. These effects are directly correlated with blockage of glycolysis. Furthermore, BP and SCT can induce the characteristic manifestations of mitochondria-regulated apoptosis, such as down-regulation of anti-apoptosis proteins Bcl-2 and Survivin, up-regulation of pro-apoptosis protein Bax, activation of caspase-3, as well as leakage of cytochrome c (Cyt-c). In summary, our results provided evidences that BP and SCT inhibit the MGC-803 cells growth and proliferation might be correlated with inhibiting glycolysis and promoting mitochondria-regulated apoptosis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. 3-Bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth

    PubMed Central

    WANG, TING-AN; ZHANG, XIAO-DONG; GUO, XING-YU; XIAN, SHU-LIN; LU, YUN-FEI

    2016-01-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT. PMID:26708213

  13. 3-bromopyruvate and sodium citrate target glycolysis, suppress survivin, and induce mitochondrial-mediated apoptosis in gastric cancer cells and inhibit gastric orthotopic transplantation tumor growth.

    PubMed

    Wang, Ting-An; Zhang, Xiao-Dong; Guo, Xing-Yu; Xian, Shu-Lin; Lu, Yun-Fei

    2016-03-01

    Glycolysis is the primary method utilized by cancer cells to produce the energy (adenosine triphosphate, ATP) required for cell proliferation. Therefore, inhibition of glycolysis may inhibit tumor growth. We previously found that both 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) can inhibit glycolysis in vitro; however, the underlying inhibitory mechanisms remain unclear. In the present study, we used a human gastric cancer cell line (SGC-7901) and an orthotopic transplantation tumor model in nude mice to explore the specific mechanisms of 3-BrPA and SCT. We found that both 3-BrPA and SCT effectively suppressed cancer cell proliferation, arrested the cell cycle, induced apoptosis, and decreased the production of lactate and ATP. 3-BrPA significantly reduced the glycolytic enzyme hexokinase activity, while SCT selectively inhibited phosphofructokinase-1 activity. Furthermore, 3-BrPA and SCT upregulated the expression of pro-apoptotic proteins (Bax, cytochrome c, and cleaved caspase-3) and downregulated the expression of anti-apoptotic proteins (Bcl-2 and survivin). Finally, our animal model of gastric cancer indicated that intraperitoneal injection of 3-BrPA and SCT suppressed orthotopic transplantation tumor growth and induced tumor apoptosis. Taken together, these results suggest that 3-BrPA and SCT selectively suppress glycolytic enzymes, decrease ATP production, induce mitochondrial-mediated apoptosis, downregulate survivin, and inhibit tumor growth. Moreover, an intraperitoneal injection is an effective form of administration of 3-BrPA and SCT.

  14. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate

    PubMed Central

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  15. Inhibition of collagen synthesis by select calcium and sodium channel blockers can be mitigated by ascorbic acid and ascorbyl palmitate.

    PubMed

    Ivanov, Vadim; Ivanova, Svetlana; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2016-01-01

    Calcium, sodium and potassium channel blockers are widely prescribed medications for a variety of health problems, most frequently for cardiac arrhythmias, hypertension, angina pectoris and other disorders. However, chronic application of channel blockers is associated with numerous side effects, including worsening cardiac pathology. For example, nifedipine, a calcium-channel blocker was found to be associated with increased mortality and increased risk for myocardial infarction. In addition to the side effects mentioned above by different channel blockers, these drugs can cause arterial wall damage, thereby contributing to vascular wall structure destabilization and promoting events facilitating rupture of plaques. Collagen synthesis is regulated by ascorbic acid, which is also essential for its optimum structure as a cofactor in lysine and proline hydroxylation, a precondition for optimum crosslinking of collagen and elastin. Therefore, the main objective in this study was to evaluate effects of various types of channel blockers on intracellular accumulation and cellular functions of ascorbate, specifically in relation to formation and extracellular deposition of major collagen types relevant for vascular function. Effects of select Na- and Ca- channel blockers on collagen synthesis and deposition were evaluated in cultured human dermal fibroblasts and aortic smooth muscle cells by immunoassay. All channel blockers tested demonstrated inhibitory effects on collagen type I deposition to the ECM by fibroblasts, each to a different degree. Ascorbic acid significantly increased collagen I ECM deposition. Nifedipine (50 µM), a representative of channel blockers tested, significantly reduced ascorbic acid and ascorbyl palmitate-dependent ECM deposition of collagen type l and collagen type lV by cultured aortic smooth muscle cells. In addition, nifedipine (50 µM) significantly reduced ascorbate-dependent collagen type l and type lV synthesis by cultured aortic smooth

  16. Gastrointestinal Inhibition of Sodium-Hydrogen Exchanger 3 Reduces Phosphorus Absorption and Protects against Vascular Calcification in CKD.

    PubMed

    Labonté, Eric D; Carreras, Christopher W; Leadbetter, Michael R; Kozuka, Kenji; Kohler, Jill; Koo-McCoy, Samantha; He, Limin; Dy, Edward; Black, Deborah; Zhong, Ziyang; Langsetmo, Ingrid; Spencer, Andrew G; Bell, Noah; Deshpande, Desiree; Navre, Marc; Lewis, Jason G; Jacobs, Jeffrey W; Charmot, Dominique

    2015-05-01

    In CKD, phosphate retention arising from diminished GFR is a key early step in a pathologic cascade leading to hyperthyroidism, metabolic bone disease, vascular calcification, and cardiovascular mortality. Tenapanor, a minimally systemically available inhibitor of the intestinal sodium-hydrogen exchanger 3, is being evaluated in clinical trials for its potential to (1) lower gastrointestinal sodium absorption, (2) improve fluid overload-related symptoms, such as hypertension and proteinuria, in patients with CKD, and (3) reduce interdialytic weight gain and intradialytic hypotension in ESRD. Here, we report the effects of tenapanor on dietary phosphorous absorption. Oral administration of tenapanor or other intestinal sodium-hydrogen exchanger 3 inhibitors increased fecal phosphorus, decreased urine phosphorus excretion, and reduced [(33)P]orthophosphate uptake in rats. In a rat model of CKD and vascular calcification, tenapanor reduced sodium and phosphorus absorption and significantly decreased ectopic calcification, serum creatinine and serum phosphorus levels, circulating phosphaturic hormone fibroblast growth factor-23 levels, and heart mass. These results indicate that tenapanor is an effective inhibitor of dietary phosphorus absorption and suggest a new approach to phosphate management in renal disease and associated mineral disorders. Copyright © 2015 by the American Society of Nephrology.

  17. Synthetic aspects, spectral, thermal studies and antimicrobial screening on bis(N,N-dimethyldithiocarbamato-S,S')antimony(III) complexes with oxo or thio donor ligands.

    PubMed

    Chauhan, H P S; Carpenter, Jaswant; Joshi, Sapana

    2014-09-15

    The bis(N,N-dimethyldithiocarbamato-S,S')antimony(III) complexes have been obtained by the reaction of chloro bis(N,N-dimethyldithiocarbamato-S,S')antimony(III) with corresponding oxo or thio donor ligands such as sodium benzoate 1, sodium thioglycolate 2, phenol 3, sodium 1-propanethiolate 4, potassium thioacetate 5, sodium salicylate 6, ethane-1,2-dithiolate 7 and disodium oxalate 8. These complexes have been characterized by the physicochemical [melting point, molecular weight determination and elemental analysis (C, H, N, S and Sb)], spectral [UV-Visible, FT-IR, far IR, NMR (1H and 13C)], thermogravimetric (TG & DTA) analysis, ESI-Mass and powder X-ray diffraction studies. Thermogravimetric analysis of the complexes confirmed the final decomposition product as highly pure antimony sulfide (Sb2S3) and powder X-ray diffraction studies show that the complexes are in lower symmetry with monoclinic crystal lattice and nano-ranged particle size (11.51-20.82 nm). The complexes have also been screened against some bacterial and fungal strains for their antibacterial and antifungal activities and compared with standard drugs. These show that the complexes have greater activities against some human pathogenic bacteria and fungi than the activities of standard drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Synthetic aspects, spectral, thermal studies and antimicrobial screening on bis(N,N-dimethyldithiocarbamato-S,S‧)antimony(III) complexes with oxo or thio donor ligands

    NASA Astrophysics Data System (ADS)

    Chauhan, H. P. S.; Carpenter, Jaswant; Joshi, Sapana

    2014-09-01

    The bis(N,N-dimethyldithiocarbamato-S,S‧)antimony(III) complexes have been obtained by the reaction of chloro bis(N,N-dimethyldithiocarbamato-S,S‧)antimony(III) with corresponding oxo or thio donor ligands such as sodium benzoate 1, sodium thioglycolate 2, phenol 3, sodium 1-propanethiolate 4, potassium thioacetate 5, sodium salicylate 6, ethane-1,2-dithiolate 7 and disodium oxalate 8. These complexes have been characterized by the physicochemical [melting point, molecular weight determination and elemental analysis (C, H, N, S and Sb)], spectral [UV-Visible, FT-IR, far IR, NMR (1H and 13C)], thermogravimetric (TG & DTA) analysis, ESI-Mass and powder X-ray diffraction studies. Thermogravimetric analysis of the complexes confirmed the final decomposition product as highly pure antimony sulfide (Sb2S3) and powder X-ray diffraction studies show that the complexes are in lower symmetry with monoclinic crystal lattice and nano-ranged particle size (11.51-20.82 nm). The complexes have also been screened against some bacterial and fungal strains for their antibacterial and antifungal activities and compared with standard drugs. These show that the complexes have greater activities against some human pathogenic bacteria and fungi than the activities of standard drugs.

  19. In vitro characterization of luseogliflozin, a potent and competitive sodium glucose co-transporter 2 inhibitor: Inhibition kinetics and binding studies.

    PubMed

    Uchida, Saeko; Mitani, Akiko; Gunji, Emi; Takahashi, Teisuke; Yamamoto, Koji

    2015-05-01

    In this study, we evaluated an inhibition model of luseogliflozin on sodium glucose co-transporter 2 (SGLT2). We also analyzed the binding kinetics of the drug to SGLT2 protein using [(3)H]-luseogliflozin. Luseogliflozin competitively inhibited human SGLT2 (hSGLT2)-mediated glucose uptake with a Ki value of 1.10 nM. In the absence of glucose, [(3)H]-luseogliflozin exhibited a high affinity for hSGLT2 with a Kd value of 1.3 nM. The dissociation half-time was 7 h, suggesting that luseogliflozin dissociates rather slowly from hSGLT2. These profiles of luseogliflozin might contribute to the long duration of action of this drug. Copyright © 2015 Taisho Pharmaceutical Co., Ltd. Production and hosting by Elsevier B.V. All rights reserved.

  20. Antimony ore in the Fairbanks district, Alaska

    USGS Publications Warehouse

    Killeen, Pemberton Lewis; Mertie, John B.

    1951-01-01

    Antimony-bearing ores in the Fairbanks district, Alaska, are found principally in two areas, the extremities of which are at points 10 miles west and 23 miles northeast of Fairbanks; and one of two minor areas lies along this same trend 30 miles farther to the northeast. These areas are probably only local manifestations of mineralization that affected a much broader area and formed antimony-bearing deposits in neighboring districts, the closest of which is 50 miles away. The ores were exposed largely as a result of lode gold mining, but at two periods in the past, high prices for antimony ore warranted an independent production and about 2500 tons of stibnite ore was shipped. The sulfide deposits occupy the same fractures along which a gold-quartz mineralization of greater economic importance occurred; and both are probably genetically related to igneous rocks which intrude the schistose country rock. The sulfide is in part contemporaneous with some late-stage quartz in which it occurs as disseminated crystals; and in part the latest filling in the mineralized zones where it forms kidney-shaped masses of essentially solid sulfide. One extremely long mass must have contained nearly 100 tons of ore, but the average of the larger kidneys is closer to several tons. Much of the ore is stibnite, with quartz as a minor impurity, and assays show the tenor to vary from 40 to 65 percent antimony. Sulphantimonites are less abundant but likewise occur as disseminated crystals and as kidney-shaped bodies. Antimony oxides appear on the weathered surface and along fractures within the sulfide ore. Deposits containing either stibnite or sulphantimonite are known at more than 50 localities, but only eighteen have produced ore and the bulk of this came from the mines. The geology of the deposit, and the nature, extent, and period of the workings are covered in the detailed descriptions of individual occurrences. Several geologic and economic factors, which greatly affect

  1. Dietary Na+ inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y2-receptor tone

    PubMed Central

    Pochynyuk, Oleh; Rieg, Timo; Bugaj, Vladislav; Schroth, Jana; Fridman, Alla; Boss, Gerry R.; Insel, Paul A.; Stockand, James D.; Vallon, Volker

    2010-01-01

    Apical release of ATP and UTP can activate P2Y2 receptors in the aldosterone-sensitive distal nephron (ASDN) and inhibit the open probability (Po) of the epithelial sodium channel (ENaC). Little is known, however, about the regulation and physiological relevance of this system. Patch-clamp studies in freshly isolated ASDN provide evidence that increased dietary Na+ intake in wild-type mice lowers ENaC Po, consistent with a contribution to Na+ homeostasis, and is associated with increased urinary concentrations of UTP and the ATP hydrolytic product, ADP. Genetic deletion of P2Y2 receptors in mice (P2Y2−/−; littermates to wild-type mice) or inhibition of apical P2Y-receptor activation in wild-type mice prevents dietary Na+-induced lowering of ENaC Po. Although they lack suppression of ENaC Po by dietary NaCl, P2Y2−/− mice do not exhibit NaCl-sensitive blood pressure, perhaps as a consequence of compensatory down-regulation of aldosterone levels. Consistent with this hypothesis, clamping mineralocorticoid activity at high levels unmasks greater ENaC activity and NaCl sensitivity of blood pressure in P2Y2−/− mice. The studies indicate a key role of the apical ATP/UTP-P2Y2-receptor system in the inhibition of ENaC Po in the ASDN in response to an increase in Na+ intake, thereby contributing to NaCl homeostasis and blood pressure regulation.—Pochynyuk, O., Rieg, T., Bugaj, V., Schroth, J., Fridman, A., Boss, G. R., Insel, P. A., Stockand, J. D., Vallon, V. Dietary Na+ inhibits the open probability of the epithelial sodium channel in the kidney by enhancing apical P2Y2-receptor tone. PMID:20097874

  2. Delphinol® standardized maqui berry extract reduces postprandial blood glucose increase in individuals with impaired glucose regulation by novel mechanism of sodium glucose cotransporter inhibition.

    PubMed

    Hidalgo, J; Flores, C; Hidalgo, M A; Perez, M; Yañez, A; Quiñones, L; Caceres, D D; Burgos, R A

    2014-06-01

    The impetus of our study was to investigate the effects of a nutritional supplement Delphinol®, an extract of maqui berries (Aristotelia chilensis) standardised to ≥25% delphinidins and ≥35% total anthocyanins, on postprandial blood glucose and insulin levels and identify the physiologic mechanism involved. Postprandial blood glucose and insulin were investigated in double-blind, placebo-controlled, cross-over fashion in ten volunteers with moderate glucose intolerance. Longer term effects on blood sugar levels were investigated in streptozotocin-diabetic rats over a four months period. Effects of maqui berry delphinidins on sodium-glucose symport were examined in rodent jejenum of the small intestine. Delphinol® intake prior to rice consumption statistical significantly lowered post prandial blood glucose and insulin as compared to placebo. We identified an inhibition of Na+-dependant glucose transport by delphinidin, the principal polyphenol to which Delphinol® is standardised. In a diabetic rat model the daily oral application of Delphinol® over a period of four months significantly lowered fasting blood glucose levels and reached values indistinguishable from healthy non-diabetic rats. Our results suggest a potential use of Delphinol® for naturally controlling post-prandial blood glucose owed to inhibition of sodium glucose co-transporter in small intestine.

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

    PubMed

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

    2015-01-01

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

  4. Disposition of antimony in rhesus monkeys infected with Leishmania braziliensis and treated with meglumine antimoniate.

    PubMed

    Friedrich, Karen; Vieira, Flávia A; Porrozzi, Renato; Marchevsky, Renato S; Miekeley, Norbert; Grimaldi, Gabriel; Paumgartten, Francisco J R

    2012-01-01

    Antimony (Sb) disposition and toxicity was evaluated in Leishmania braziliensis-infected monkeys (Macaca mulatta) treated with a 21-d course of low (LOW) or standard (STD) meglumine antimoniate (MA) dosage regimens (5 or 20 mg Sb(V)/kg body weight/d im). Antimony levels in biological matrices were determined by inductively coupled plasma mass spectrometry (ICPMS), while on-line ion chromatography coupled to ICPMS was used to separate and quantify Sb species in plasma. Nadir Sb levels rose steadily from 19.6 ± 4 and 65.1 ± 17.4 ng/g, 24 h after the first injection, up to 27.4 ± 5.8 and 95.7 ± 6.6 ng/g, 24 h after the 21st dose in LOW and SDT groups, respectively. Subsequently, Sb plasma levels gradually declined with a terminal elimination phase half-life of 35.8 d. Antimony speciation in plasma on posttreatment days 1-9 indicated that as total Sb levels declined, proportion of Sb(V) remained nearly constant (11-20%), while proportion of Sb(III) rose from 5% (d 1) to 50% (d 9). Plasma [Sb]/erythrocyte [Sb] ratio was >1 until 12 h after dosing and reversed thereafter. Tissue Sb concentrations (posttreatment days 55 and 95) were as follows: >1000 ng/g in thyroid, nails, liver, gall bladder and spleen; >200 and <1000 ng/g in lymph nodes, kidneys, adrenals, bones, skeletal muscles, heart and skin; and <200 ng/g in various brain structures, thymus, stomach, colon, pancreas. and teeth. Results from this study are therefore consistent with view that Sb(V) is reduced to Sb(III), the active form, within cells from where it is slowly eliminated. Localization of Sb active forms in the thyroid gland and liver and the pathophysiological consequences of marked Sb accumulation in these tissues warrant further studies.

  5. Inhibition of oxytocin-induced but not angiotensin-induced rat uterine contractions following exposure to sodium sulfide

    SciTech Connect

    Hayden, L.J.; Franklin, K.J.; Roth, S.H.; Moore, G.J. )

    1989-01-01

    Low concentrations of sodium sulfide reversibly attenuate the contractile response of the isolate rat uterus to oxytocin without affecting angiotensin II responsiveness. These findings suggest that functionally important disulfide bonds in the rat uterine oxytocin receptor, but not the angiotensin receptor, are sensitive to hydrosulfide ion. Reduction of oxytocin receptors by hydrosulfide ion may be a mechanism by which low level of H{sub 2}S delay parturition in rats.

  6. Anticonvulsant effect of Rhynchophylline involved in the inhibition of persistent sodium current and NMDA receptor current in the pilocarpine rat model of temporal lobe epilepsy.

    PubMed

    Shao, Hui; Yang, Yang; Mi, Ze; Zhu, Guang-Xi; Qi, Ai-Ping; Ji, Wei-Gang; Zhu, Zhi-Ru

    2016-11-19

    Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. Several studies have demonstrated that RIN has a significant anticonvulsant effect in many types of epilepsy models in vivo. However, the mechanisms of the anticonvulsant effect remain elusive. Using combined methods of behavioral testing, immunofluorescence and electrophysiological recordings, we characterized the anticonvulsant effect of RIN in a pilocarpine-induced status epilepticus (SE) rat model of temporal lobe epilepsy (TLE) and investigated the underlying cellular mechanisms. In one set of experiments, rats received RIN treatment prior to pilocarpine injection. In a second set of experiments, rats received RIN treatment following the onset of stage 3 seizures. Pretreatment and posttreatment with RIN effectively reduced the seizure severity in the acute phase of TLE. Furthermore, RIN protected medial entorhinal cortex (mEC) layer III neurons from neuronal death and terminated spontaneous epileptiform discharge of mEC layer II neurons in SE-experienced rats. Whole-cell voltage-clamp recordings indicated that RIN inhibited neuronal hyperexcitability via inhibition of the persistent sodium current (INaP) and NMDA receptor current. Immunofluorescence experiments also demonstrated that RIN rectified the pilocarpine-induced upregulation of Nav1.6 and NR2B protein expression. In conclusion, our results identified RIN as an anticonvulsant agent that inhibited ictal discharge via INap and NMDA receptor current inhibition. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Antimony film sensor for sensitive rare earth metal analysis in environmental samples.

    PubMed

    Makombe, Martin; van der Horst, Charlton; Silwana, Bongiwe; Iwuoha, Emmanuel; Somerset, Vernon

    2016-07-02

    A sensor for the adsorptive stripping voltammetric determination of rare earth elements has been developed. The electrochemical procedure is based on the oxidation of the rare earth elements complexed with alizarin complexone at a glassy carbon electrode that was in situ modified with an antimony film, during an anodic scan from -0.2 V to 1.1 V (vs. Ag/AgCl) and deposition potential of -0.1 V (vs. Ag/AgCl). The factors influencing the adsorptive stripping capability were optimised, including the complexing agent concentration, plating concentration of antimony and deposition time. The detection of rare earth elements (La, Ce and Pr) were realised in 0.08 M sodium acetate (pH = 5.8) solution as supporting electrolyte, with 2 × 10(-6) M alizarin complexone and 1.0 mg L(-1) antimony solution. Under the optimised conditions, a deposition time of 360 s was obtained and a linear response was observed between 1 and 25 µg L(-1). The reproducibility of the voltammetric measurements was found to be within 5.0% RSD for 12 replicate measurements of cerium(III) concentration of 5 µg L(-1) using the same electrode surface. The detection limits obtained using stripping analysis was 0.06, 0.42 and 0.71 μg L(-1) for Ce(III), La(III) and Pr(III), respectively. The developed sensor has been successfully applied for the determination of cerium, lanthanum and praseodymium in municipal tap water samples.

  8. Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species

    PubMed Central

    Andrade, Juvana M.; Baba, Elio H.; Machado-de-Avila, Ricardo A.; Chavez-Olortegui, Carlos; Demicheli, Cynthia P.; Frézard, Frédéric

    2016-01-01

    Antimony (Sb) resistance in leishmaniasis chemotherapy has become one of the major challenges to the control of this spreading worldwide public health problem. Since the plasma membrane pore-forming protein aquaglyceroporin 1 (AQP1) is the major route of Sb uptake in Leishmania, functional studies are relevant to characterize drug transport pathways in the parasite. We generated AQP1-overexpressing Leishmania guyanensis and L. braziliensis mutants and investigated their susceptibility to the trivalent form of Sb (SbIII) in the presence of silver and nitrate salts. Both AQP1-overexpressing lines presented 3- to 4-fold increased AQP1 expression levels compared with those of their untransfected counterparts, leading to an increased SbIII susceptibility of about 2-fold. Competition assays using silver nitrate, silver sulfadiazine, or silver acetate prior to SbIII exposure increased parasite growth, especially in AQP1-overexpressing mutants. Surprisingly, SbIII-sodium nitrate or SbIII-potassium nitrate combinations showed significantly enhanced antileishmanial activities compared to those of SbIII alone, especially against AQP1-overexpressing mutants, suggesting a putative nitrate-dependent modulation of AQP1 activity. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed that the concomitant exposure to SbIII and nitrate favors antimony accumulation in the parasite, increasing the toxicity of the drug and culminating with parasite death. This is the first report showing evidence of AQP1-mediated SbIII susceptibility modulation by silver in Leishmania and suggests the potential antileishmanial activity of the combination of nitrate salts and SbIII. PMID:27161624

  9. Silver and Nitrate Oppositely Modulate Antimony Susceptibility through Aquaglyceroporin 1 in Leishmania (Viannia) Species.

    PubMed

    Andrade, Juvana M; Baba, Elio H; Machado-de-Avila, Ricardo A; Chavez-Olortegui, Carlos; Demicheli, Cynthia P; Frézard, Frédéric; Monte-Neto, Rubens L; Murta, Silvane M F

    2016-08-01

    Antimony (Sb) resistance in leishmaniasis chemotherapy has become one of the major challenges to the control of this spreading worldwide public health problem. Since the plasma membrane pore-forming protein aquaglyceroporin 1 (AQP1) is the major route of Sb uptake in Leishmania, functional studies are relevant to characterize drug transport pathways in the parasite. We generated AQP1-overexpressing Leishmania guyanensis and L. braziliensis mutants and investigated their susceptibility to the trivalent form of Sb (Sb(III)) in the presence of silver and nitrate salts. Both AQP1-overexpressing lines presented 3- to 4-fold increased AQP1 expression levels compared with those of their untransfected counterparts, leading to an increased Sb(III) susceptibility of about 2-fold. Competition assays using silver nitrate, silver sulfadiazine, or silver acetate prior to Sb(III) exposure increased parasite growth, especially in AQP1-overexpressing mutants. Surprisingly, Sb(III)-sodium nitrate or Sb(III)-potassium nitrate combinations showed significantly enhanced antileishmanial activities compared to those of Sb(III) alone, especially against AQP1-overexpressing mutants, suggesting a putative nitrate-dependent modulation of AQP1 activity. The intracellular level of antimony quantified by graphite furnace atomic absorption spectrometry showed that the concomitant exposure to Sb(III) and nitrate favors antimony accumulation in the parasite, increasing the toxicity of the drug and culminating with parasite death. This is the first report showing evidence of AQP1-mediated Sb(III) susceptibility modulation by silver in Leishmania and suggests the potential antileishmanial activity of the combination of nitrate salts and Sb(III).

  10. Sodium tanshinone IIA sulfonate inhibits hypoxia-induced enhancement of SOCE in pulmonary arterial smooth muscle cells via the PKG-PPAR-γ signaling axis.

    PubMed

    Jiang, Qian; Lu, Wenju; Yang, Kai; Hadadi, Cyrus; Fu, Xin; Chen, Yuqin; Yun, Xin; Zhang, Jie; Li, Meichan; Xu, Lei; Tang, Haiyang; Yuan, Jason X-J; Wang, Jian; Sun, Dejun

    2016-07-01

    Our laboratory previously showed that sodium tanshinone IIA sulfonate (STS) inhibited store-operated Ca(2+) entry (SOCE) through store-operated Ca(2+) channels (SOCC) via downregulating the expression of transient receptor potential canonical proteins (TRPC), which contribute to the formation of SOCC (Wang J, Jiang Q, Wan L, Yang K, Zhang Y, Chen Y, Wang E, Lai N, Zhao L, Jiang H, Sun Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 48: 125-134, 2013). The detailed molecular mechanisms by which STS inhibits SOCE and downregulates TRPC, however, remain largely unknown. We have previously shown that, under hypoxic conditions, inhibition of protein kinase G (PKG) and peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling axis results in the upregulation of TRPC (Wang J, Yang K, Xu L, Zhang Y, Lai N, Jiang H, Zhang Y, Zhong N, Ran P, Lu W. Am J Respir Cell Mol Biol 49: 231-240, 2013). This suggests that strategies targeting the restoration of this signaling pathway may be an effective treatment strategy for pulmonary hypertension. In this study, our results demonstrated that STS treatment can effectively prevent the hypoxia-mediated inhibition of the PKG-PPAR-γ signaling axis in rat distal pulmonary arterial smooth muscle cells (PASMCs) and distal pulmonary arteries. These effects of STS treatment were blocked by pharmacological inhibition or specific small interfering RNA knockdown of either PKG or PPAR-γ. Moreover, targeted PPAR-γ agonist markedly enhanced the beneficial effects of STS. These results comprehensively suggest that STS treatment can prevent hypoxia-mediated increases in intracellular calcium homeostasis and cell proliferation, by targeting and restoring the hypoxia-inhibited PKG-PPAR-γ signaling pathway in PASMCs.

  11. Voltage-Independent Inhibition of the Tetrodotoxin-Sensitive Sodium Currents by Oxotremorine and Angiotensin II in Rat Sympathetic Neurons.

    PubMed

    Puente, Erika I; De la Cruz, Lizbeth; Arenas, Isabel; Elias-Viñas, David; Garcia, David E

    2016-04-01

    Tetrodotoxin-sensitive Na(+) currents have been extensively studied because they play a major role in neuronal firing and bursting. In this study, we showed that voltage-dependent Na(+) currents are regulated in a slow manner by oxotremorine (oxo-M) and angiotensin II in rat sympathetic neurons. We found that these currents can be readily inhibited through a signaling pathway mediated by G proteins and phospholipase C (PLC) β1. This inhibition is slowly established, pertussis toxin-insensitive, partially reversed within tens of seconds after oxo-M washout, and not relieved by a strong depolarization, suggesting a voltage-insensitive mechanism of inhibition. Specificity of the M1 receptor was tested by the MT-7 toxin. Activation and inactivation curves showed no shift in the voltage dependency under the inhibition by oxo-M. This inhibition is blocked by a PLC inhibitor (U73122, 1-(6-{[(17β)-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino}hexyl)-1H-pyrrole-2,5-dione), and recovery from inhibition is prevented by wortmannin, a PI3/4 kinase inhibitor. Hence, the pathway involves Gq/11 and is mediated by a diffusible second messenger. Oxo-M inhibition is occluded by screening phosphatidylinositol 4,5-bisphosphate (PIP2)-negative charges with poly-l-lysine and prevented by intracellular dialysis with a PIP2 analog. In addition, bisindolylmaleimide I, a specific ATP-competitive protein kinase C (PKC) inhibitor, rules out that this inhibition may be mediated by this protein kinase. Furthermore, oxo-M-induced suppression of Na(+) currents remains unchanged when neurons are treated with calphostin C, a PKC inhibitor that targets the diacylglycerol-binding site of the kinase. These results support a general mechanism of Na(+) current inhibition that is widely present in excitable cells through modulation of ion channels by specific G protein-coupled receptors. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Biogeochemistry of arsenic and antimony in the North Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Cutter, Gregory A.; Cutter, Lynda S.

    2006-05-01

    The biogeochemical cycles of the metalloid elements arsenic and antimony were examined along a 15,000 km surface water transect and at 9 vertical profile stations in the western North Pacific Ocean as part of the 2002 IOC Contaminant Baseline Survey. Results show that the speciation of dissolved arsenic (As III, As V, and methylated As) was subtly controlled by the arsenate (AsV)/phosphate ratio. An additional fraction of presumed organic arsenic previously reported in coastal waters was also present (˜15% of the total As) in oceanic surface waters. Dissolved inorganic antimony displayed mildly scavenged behavior that was confirmed by correlations with aluminum, but atmospheric inputs that may be anthropogenic in origin also affected its concentrations. Monomethyl antimony, the predominant organic form of the element, behaved almost conservatively throughout the water column, radically changing the known biogeochemical cycle of antimony.

  13. Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside induced lipid peroxidation in rats' pancreas by phenolic extracts of avocado pear leaves and fruit.

    PubMed

    Oboh, Ganiyu; Isaac, Adelusi Temitope; Akinyemi, Ayodele Jacobson; Ajani, Richard Akinlolu

    2014-09-01

    Persea americana fruit and leaves had been known in folk medicine for their anti-diabetic prowess. Therefore, this study sought to investigate the inhibitory effect of phenolic extract from avocado pear (Persea americana) leaves and fruits on some key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase); and sodium nitroprusside (SNP) induced lipid peroxidation in rats' pancreas in vitro. The phenolic extracts of Persea americana fruit and leaves were extracted using methanol and 1M HCl (1:1 v/v). Thereafter, their inhibitory effects on sodium nitroprusside induced lipid peroxidation and key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) were determined in vitro. The result revealed that the leaves had fruit of avocado pear inhibit both α-amylase and α-glucosidase activities in a dose dependent manner. However, the Peel had the highest α-amylase inhibitory activity while the leaf had the highest α-glucosidase inhibitory activity as revealed by their IC50 value. Furthermore, incubation of the rat pancreas in the presence of 5 mM SNP caused an increase in the malondialdehyde (MDA) content in the tissue, however, introduction of the phenolic extracts inhibited MDA produced in a dose dependent manner. The additive and/or synergistic action of major phenolic compounds such as syringic acid, eugenol, vnillic acid, isoeugenol, guaiacol, kaemferol, catechin, ρ-hydroxybenzoic acid, ferulic acid, apigenin, naringenin, epigallocatechin, epicatechin, lupeol and epigallocatechin-3-O-gallate in avocado pear using gas chromatography (GC) could have contributed to the observed medicinal properties of the plant. Therefore, inhibition of some key enzymes linked to type 2 diabetes and prevention of oxidative stress in the pancreas could be some of the possible mechanism by which they exert their anti-diabetic properties.

  14. Hydrogen sulfide decreases β-adrenergic agonist-stimulated lung liquid clearance by inhibiting ENaC-mediated transepithelial sodium absorption.

    PubMed

    Agné, Alisa M; Baldin, Jan-Peter; Benjamin, Audra R; Orogo-Wenn, Maria C; Wichmann, Lukas; Olson, Kenneth R; Walters, Dafydd V; Althaus, Mike

    2015-04-01

    In pulmonary epithelia, β-adrenergic agonists regulate the membrane abundance of the epithelial sodium channel (ENaC) and, thereby, control the rate of transepithelial electrolyte absorption. This is a crucial regulatory mechanism for lung liquid clearance at birth and thereafter. This study investigated the influence of the gaseous signaling molecule hydrogen sulfide (H2S) on β-adrenergic agonist-regulated pulmonary sodium and liquid absorption. Application of the H2S-liberating molecule Na2S (50 μM) to the alveolar compartment of rat lungs in situ decreased baseline liquid absorption and abrogated the stimulation of liquid absorption by the β-adrenergic agonist terbutaline. There was no additional effect of Na2S over that of the ENaC inhibitor amiloride. In electrophysiological Ussing chamber experiments with native lung epithelia (Xenopus laevis), Na2S inhibited the stimulation of amiloride-sensitive current by terbutaline. β-adrenergic agonists generally increase ENaC abundance by cAMP formation and activation of PKA. Activation of this pathway by forskolin and 3-isobutyl-1-methylxanthine increased amiloride-sensitive currents in H441 pulmonary epithelial cells. This effect was inhibited by Na2S in a dose-dependent manner (5-50 μM). Na2S had no effect on cellular ATP concentration, cAMP formation, and activation of PKA. By contrast, Na2S prevented the cAMP-induced increase in ENaC activity in the apical membrane of H441 cells. H441 cells expressed the H2S-generating enzymes cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, and they produced H2S amounts within the employed concentration range. These data demonstrate that H2S prevents the stimulation of ENaC by cAMP/PKA and, thereby, inhibits the proabsorptive effect of β-adrenergic agonists on lung liquid clearance.

  15. Inhibition of Key Enzymes Linked to Type 2 Diabetes and Sodium Nitroprusside Induced Lipid Peroxidation in Rats’ Pancreas by Phenolic Extracts of Avocado Pear Leaves and Fruit

    PubMed Central

    Oboh, Ganiyu; Isaac, Adelusi Temitope; Akinyemi, Ayodele Jacobson; Ajani, Richard Akinlolu

    2014-01-01

    Persea americana fruit and leaves had been known in folk medicine for their anti-diabetic prowess. Therefore, this study sought to investigate the inhibitory effect of phenolic extract from avocado pear (Persea americana) leaves and fruits on some key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase); and sodium nitroprusside (SNP) induced lipid peroxidation in rats’ pancreas in vitro. The phenolic extracts of Persea americana fruit and leaves were extracted using methanol and 1M HCl (1:1 v/v). Thereafter, their inhibitory effects on sodium nitroprusside induced lipid peroxidation and key enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) were determined in vitro. The result revealed that the leaves had fruit of avocado pear inhibit both α-amylase and α-glucosidase activities in a dose dependent manner. However, the Peel had the highest α-amylase inhibitory activity while the leaf had the highest α-glucosidase inhibitory activity as revealed by their IC50 value. Furthermore, incubation of the rat pancreas in the presence of 5 mM SNP caused an increase in the malondialdehyde (MDA) content in the tissue, however, introduction of the phenolic extracts inhibited MDA produced in a dose dependent manner. The additive and/or synergistic action of major phenolic compounds such as syringic acid, eugenol, vnillic acid, isoeugenol, guaiacol, kaemferol, catechin, ρ-hydroxybenzoic acid, ferulic acid, apigenin, naringenin, epigallocatechin, epicatechin, lupeol and epigallocatechin-3-O-gallate in avocado pear using gas chromatography (GC) could have contributed to the observed medicinal properties of the plant. Therefore, inhibition of some key enzymes linked to type 2 diabetes and prevention of oxidative stress in the pancreas could be some of the possible mechanism by which they exert their anti-diabetic properties PMID:25324703

  16. Antimony and sleep-related disorders: NHANES 2005-2008.

    PubMed

    Scinicariello, Franco; Buser, Melanie C; Feroe, Aliya G; Attanasio, Roberta

    2017-07-01

    Antimony is used as a flame-retardant in textiles and plastics, in semiconductors, pewter, and as pigments in paints, lacquers, glass and pottery. Subacute or chronic antimony poisoning has been reported to cause sleeplessness. The prevalence of short sleep duration (<7h/night) has been reported to be 37.1% in the general US population, and obstructive sleep apnea (OSA) affects 12-28 million US adults. Insufficient sleep and OSA have been linked to the development of several chronic conditions including diabetes, cardiovascular disease, obesity and depression, conditions that pose serious public health threats. To investigate whether there is an association between antimony exposure and sleep-related disorders in the US adult population using the National Health and Nutrition Examination Survey (NHANES) 2005-2008. We performed multivariate logistic regression to analyze the association of urinary antimony with several sleep disorders, including insufficient sleep and OSA, in adult (ages 20 years and older) participants of NHANES 2005-2008 (n=2654). We found that participants with higher urinary antimony levels had higher odds to experience insufficient sleep (≤6h/night) (OR 1.73; 95%CI; 1.04, 2.91) as well as higher odds to have increased sleep onset latency (>30min/night). Furthermore, we found that higher urinary antimony levels in participants were associated with OSA (OR 1.57; 95%CI; 1.05, 2.34), sleep problems, and day-time sleepiness. In this study, we found that urinary antimony was associated with higher odds to have insufficient sleep and OSA. Because of the public health implications of sleep disorders, further studies, especially a prospective cohort study, are warranted to evaluate the association between antimony exposure and sleep-related disorders. Copyright © 2017. Published by Elsevier Inc.

  17. Characterization of the Antimonial Antileishmanial Agent Meglumine Antimonate (Glucantime)

    PubMed Central

    Roberts, William L.; McMurray, Walter J.; Rainey, Petrie M.

    1998-01-01

    Meglumine antimonate (Glucantime), a drug of choice for the treatment of leishmaniasis, is produced by the reaction of pentavalent antimony with N-methyl-d-glucamine, a carbohydrate derivative. We investigated the structure and composition of meglumine antimonate, which remain poorly understood, despite 50 years of use. Measurement of the antimony content of meglumine antimonate powder indicated a 1:1.37 molar ratio of antimony to N-methyl-d-glucamine. Osmolality measurements performed with meglumine antimonate solutions demonstrated an average of 1.43 antimony atoms per molecule of meglumine antimonate. The osmolality of a 1:10 dilution of stock meglumine antimonate increased by 45% over 8 days, suggesting hydrolysis to less complex species. A comparison of the proton nuclear magnetic resonance spectra of N-methyl-d-glucamine and meglumine antimonate revealed an increase in complexity in the latter but with all of the resonances of the former still being evident, consistent with the presence of coordination complexes between antimony and each of the N-methyl-d-glucamine hydroxyls. Fast atom bombardment and electrospray ionization mass spectrometry coupled with several derivatization procedures provided evidence that up to four N-methyl-d-glucamine hydroxyls are coordinated with each antimony. A series of oligomers were observed. The major moiety has a molecular mass of 507 atomic mass units and consists of NMG-Sb-NMG, where Sb represents antimony and NMG represents N-methyl-d-glucamine. Additional species containing up to four antimony atoms and five N-methyl-d-glucamine moieties and corresponding to the general form (NMG-Sb)n-NMG are also present. These results suggest that this agent is a complex mixture that exists in equilibrium in aqueous solution. PMID:9593130

  18. Alpha2-adrenoceptor-independent inhibition of acetylcholine receptor channel and sodium channel by dexmedetomidine in rat superior cervical ganglion neurons.

    PubMed

    Yang, L; Tang, J; Dong, J; Zheng, J

    2015-03-19

    Both central and peripheral sympathetic nervous systems contribute to the cardiovascular effects of dexmedetomidine (DMED), a highly selective and widely used a2-adrenoceptor agonist for sedation, analgesia, and stress management. The central sympatholytic effects are augmented by peripheral inhibition of sympathetic ganglion transmission. The mechanism is not clear. In this research, using conventional patch-clamp recordings we investigated the direct effects of DMED on sodium (Na(+)) channel currents (INa) and nicotinic acetylcholine (ACh) receptor (nAChRs) channel currents (IACh) in rat superior cervical ganglion (SCG) neurons to explore the possible mechanisms of sympathetic ganglion transmission inhibition by DMED. DMED voltage-dependently suppressed INa with half maximal inhibitory concentration (IC50) values of 67.2±9.6μM and 26.1±5.3μM at holding potentials of -80mV and -60mV, respectively. The inhibition of Na(+) channels by DMED was also frequency dependent. 100μM DMED shifted the Na(+) channel inactivation curves to the hyperpolarizing direction by 9.8mV (P<0.01) and slowed the recovery from inactivation by 8.9ms (P<0.01), but no effects were seen on the shape of the current-voltage relationship or Na(+) channels activation curves. DMED dose-dependently inhibited IACh with an IC50 value of 5.5±2.4μM in SCG neurons, and this inhibition was voltage-independent. DMED pretreatment followed by fast co-application of DMED and ACh produced a significantly larger IACh inhibition than without DMED pretreatment. Yohimbine, phentolamine, and atropine pretreatment did not alter the inhibitory effects of DMED on INa and IACh. In conclusion, DMED dose-dependently inhibits INa and IACh in rat SCG neurons by preferential binding to the inactivated state of the Na(+) channels and the closed state (resting) of nAChR channels respectively. Both inhibitions are a2-adrenoceptor independent. Furthermore, the nAChR channels in rat SCG neurons are much more sensitive to

  19. Microbial Methylation of Metalloids: Arsenic, Antimony, and Bismuth

    PubMed Central

    Bentley, Ronald; Chasteen, Thomas G.

    2002-01-01

    A significant 19th century public health problem was that the inhabitants of many houses containing wallpaper decorated with green arsenical pigments experienced illness and death. The problem was caused by certain fungi that grew in the presence of inorganic arsenic to form a toxic, garlic-odored gas. The garlic odor was actually put to use in a very delicate microbiological test for arsenic. In 1933, the gas was shown to be trimethylarsine. It was not until 1971 that arsenic methylation by bacteria was demonstrated. Further research in biomethylation has been facilitated by the development of delicate techniques for the determination of arsenic species. As described in this review, many microorganisms (bacteria, fungi, and yeasts) and animals are now known to biomethylate arsenic, forming both volatile (e.g., methylarsines) and nonvolatile (e.g., methylarsonic acid and dimethylarsinic acid) compounds. The enzymatic mechanisms for this biomethylation are discussed. The microbial conversion of sodium arsenate to trimethylarsine proceeds by alternate reduction and methylation steps, with S-adenosylmethionine as the usual methyl donor. Thiols have important roles in the reductions. In anaerobic bacteria, methylcobalamin may be the donor. The other metalloid elements of the periodic table group 15, antimony and bismuth, also undergo biomethylation to some extent. Trimethylstibine formation by microorganisms is now well established, but this process apparently does not occur in animals. Formation of trimethylbismuth by microorganisms has been reported in a few cases. Microbial methylation plays important roles in the biogeochemical cycling of these metalloid elements and possibly in their detoxification. The wheel has come full circle, and public health considerations are again important. PMID:12040126

  20. Sodium arsenite-induced inhibition of cell proliferation is related to inhibition of IL-2 mRNA expression in mouse activated T cells.

    PubMed

    Conde, Patricia; Acosta-Saavedra, Leonor C; Goytia-Acevedo, Raquel C; Calderon-Aranda, Emma S

    2007-04-01

    A proposed mechanism for the As-induced inhibition of cell proliferation is the inhibition of IL-2 secretion. However, the effects of arsenite on IL-2 mRNA expression or on the ERK pathway in activated-T cells have not yet been described. We examined the effect of arsenite on IL-2 mRNA expression, cell activation and proliferation in PHA-stimulated murine lymphocytes. Arsenite (1 and 10 microM) decreased IL-2 mRNA expression, IL-2 secretion and cell proliferation. Arsenite (10 microM) strongly inhibited ERK-phosphorylation. However, the partial inhibition (50%) of IL-2 mRNA produced by 1 microM, consistent with the effects on IL-2 secretion and cell proliferation, could not be explained by the inhibition of ERK-phosphorylation, which was not affected at this concentration. The inhibition of IL-2 mRNA expression caused by 1 microM could be associated to effects on pathways located downstream or parallel to ERK. Arsenite also decreased early activation (surface CD69+ expression) in both CD4+ and CD8+, and decreased total CD8+ count without significantly affecting CD4+, supporting that the cellular immune response mediated by cytotoxic T cells is an arsenic target. Thus, our results suggest that arsenite decreases IL-2 mRNA levels and T-cell activation and proliferation. However, further studies on the effects of arsenite on IL-2 gene transcription and IL-2 mRNA stability are needed.

  1. [Side effects of meglumine antimoniate in cutaneous leishmaniasis: 15 cases].

    PubMed

    Ezzine Sebai, Nadia; Mrabet, Nozha; Khaled, Aida; Zeglaoui, Faten; Kharfi, Monia; Fazaa, Bécima; Kamoun, Mohamed Ridha

    2010-01-01

    Leishmaniasis is wide spread parasitic disease considered to be endemic in 88 countries in both old and new world. The standard treatment remains Meglumine antimoniate. We study the side effects of systemic meglumine antimoniate in cutaneous leishmaniasis. We conduct a retrospective study covering 3-year period (2002- 2005). All medical reports of cutaneous leishmaniasis treated by systemic Meglumine antimoniate are reviewed. The study comprise 63 patients all treated by systemic meglumine antimoniate at the dose of 60 mg/kg/day for 10-15 days. Side effects were noted in 15 cases (12 females and 3 males). The subject's age range from 11 to 78 years. Stibio-intolerance (fever, rash, arthralgia, abdominal pain) was observed in 12 cases and stibiotoxicity in 3 cases: precordialgies 1 case, hyperamylasemia and increase liver enzyme: 1 case, pancytopenia, renal and hepatic failure leading to death: 1 case, skin eruption: 7 cases, pruritus and erythema in the site of injection: 5 cases, urticaria: 1 case. Meglumine antimoniate was stopped in 13 cases. Meglumine antimoniate is the generally recommended treatment of cutaneous leishmaniasis. In spite of the rarity of Glucantime's side effects, we recommend a careful survey especially in older patients.

  2. Reduced antimony accumulation in ARM58-overexpressing Leishmania infantum.

    PubMed

    Schäfer, Carola; Tejera Nevado, Paloma; Zander, Dorothea; Clos, Joachim

    2014-01-01

    Antimony-based drugs are still the mainstay of chemotherapy against Leishmania infections in many countries where the parasites are endemic. The efficacy of antimonials has been compromised by increasing numbers of resistant infections, the basis of which is not fully understood and likely involves multiple factors. By using a functional cloning strategy, we recently identified a novel antimony resistance marker, ARM58, from the parasite Leishmania braziliensis that protects the parasites against antimony-based antileishmanial compounds. Here we show that the Leishmania infantum homologue also confers resistance against antimony but not against other antileishmanial drugs and that its function depends critically on one of four conserved domains of unknown function. This critical domain requires at least two hydrophobic amino acids and is predicted to form a transmembrane structure. Overexpression of ARM58 in antimony-exposed parasites reduces the intracellular Sb accumulation by over 70%, indicating a role for ARM58 in Sb extrusion pathways, but without involvement of energy-dependent transporter proteins.

  3. Reduced Antimony Accumulation in ARM58-Overexpressing Leishmania infantum

    PubMed Central

    Schäfer, Carola; Tejera Nevado, Paloma; Zander, Dorothea

    2014-01-01

    Antimony-based drugs are still the mainstay of chemotherapy against Leishmania infections in many countries where the parasites are endemic. The efficacy of antimonials has been compromised by increasing numbers of resistant infections, the basis of which is not fully understood and likely involves multiple factors. By using a functional cloning strategy, we recently identified a novel antimony resistance marker, ARM58, from the parasite Leishmania braziliensis that protects the parasites against antimony-based antileishmanial compounds. Here we show that the Leishmania infantum homologue also confers resistance against antimony but not against other antileishmanial drugs and that its function depends critically on one of four conserved domains of unknown function. This critical domain requires at least two hydrophobic amino acids and is predicted to form a transmembrane structure. Overexpression of ARM58 in antimony-exposed parasites reduces the intracellular Sb accumulation by over 70%, indicating a role for ARM58 in Sb extrusion pathways, but without involvement of energy-dependent transporter proteins. PMID:24366738

  4. Voltage-dependent sodium channels in human small-cell lung cancer cells: role in action potentials and inhibition by Lambert-Eaton syndrome IgG.

    PubMed

    Blandino, J K; Viglione, M P; Bradley, W A; Oie, H K; Kim, Y I

    1995-01-01

    Sodium channels of human small-cell lung cancer (SCLC) cells were examined with whole-cell and single-channel patch clamp methods. In the tumor cells from SCLC cell line NCI-H146, the majority of the voltage-gated Na+ channels are only weakly tetrodotoxin (TTX)-sensitive (Kd = 215 nM). With the membrane potential maintained at -60 to -80 mV, these cells produced all-or-nothing action potentials in response to depolarizing current injection (> 20 pA). Similar all-or-nothing spikes were also observed with anodal break excitation. Removal of external Ca2+ did not affect the action potential production, whereas 5 microM TTX or substitution of Na+ with choline abolished it. Action potentials elicited in the Ca(2+)-free condition were reversibly blocked by 4 mM MnCl2 due to the Mn(2+)-induced inhibition of voltage-dependent sodium currents (INa). Therefore, Na+ channels, not Ca2+ channels, underlie the excitability of SCLC cells. Whole-cell INa was maximal with step-depolarizing stimulations to 0 mV, and reversed at +45.2 mV, in accord with the predicted Nernst equilibrium potential for a Na(+)-selective channel. INa evoked by depolarizing test potentials (-60 to +40 mV) exhibited a transient time course and activation/inactivation kinetics typical of neuronal excitable membranes; the plot of the Hodgkin-Huxley parameters, m infinity and h infinity, also revealed biophysical similarity between SCLC and neuronal Na+ channels. The single channel current amplitude, as measured with the inside-out patch configuration, was 1.0 pA at -20 mV with a slope conductance of 12.1 pS. The autoantibodies implicated in the Lambert-Eaton myasthenic syndrome (LES), which are known to inhibit ICa and INa in bovine adrenal chromaffin cells, also significantly inhibited INa in SCLC cells. These results indicate that (i) action potentials in human SCLC cells result from the regenerative increase in voltage-gated Na+ channel conductance; (ii) fundamental characteristics of SCLC Na+ channels

  5. Growth of antimony doped P-type zinc oxide nanowires for optoelectronics

    DOEpatents

    Wang, Zhong Lin; Pradel, Ken

    2016-09-27

    In a method of growing p-type nanowires, a nanowire growth solution of zinc nitrate (Zn(NO.sub.3).sub.2), hexamethylenetetramine (HMTA) and polyethylenemine (800 M.sub.w PEI) is prepared. A dopant solution to the growth solution, the dopant solution including an equal molar ration of sodium hydroxide (NaOH), glycolic acid (C.sub.2H.sub.4O.sub.3) and antimony acetate (Sb(CH.sub.3COO).sub.3) in water is prepared. The dopant solution and the growth solution combine to generate a resulting solution that includes antimony to zinc in a ratio of between 0.2% molar to 2.0% molar, the resulting solution having a top surface. An ammonia solution is added to the resulting solution. A ZnO seed layer is applied to a substrate and the substrate is placed into the top surface of the resulting solution with the ZnO seed layer facing downwardly for a predetermined time until Sb-doped ZnO nanowires having a length of at least 5 .mu.m have grown from the ZnO seed layer.

  6. Alkaline reforming of brominated fire-retardant plastics: fate of bromine and antimony.

    PubMed

    Onwudili, Jude A; Williams, Paul T

    2009-02-01

    High-impact polystyrene (HIPS) flame retarded with decabromodiphenyl ether (DDE), has been reacted in supercritical water from 380 to 450 degrees C and 21.5 to 31.0 MPa pressure in a batch reactor. Different concentrations of sodium hydroxide additive were used in situ to neutralize the corrosive inorganic bromine species released during the reactions. It appeared that supercritical water conditions lowered the decomposition temperature of both the fire-retardant DDE and HIPS. The reaction products included oils (up to 76 wt%), char (up to 18 wt%) and gas (up to 2.4 wt%) which was mainly methane. The presence of the alkaline water led to up to 97 wt% debromination of the product oil, producing virtually bromine-free oil feedstock. The removal of antimony from the oil product during processing was of the order of 98 wt%. The oil consisted of many single- and multiple-ringed aromatic compounds, many of which had alkyl substituents and/or aliphatic C(n)-bridges (n=1-4). The major single-ringed compounds included toluene, xylenes, ethylbenzene, propylbenzene and alpha-methylstyrene. Bibenzyl (diphenylethane), stilbene, diphenylmethane, diphenylpropane, diphenylcyclopropane, diphenylpropene, diphenylbutane, diphenylbutene and diphenylbuta-1,3-diene were the major C(n)-bridged compounds. Diphenyl ether and acetophenone were the major oxygenated compounds found. The process thus has the potential to produce bromine-free and antimony-free oils from fire-retardant plastics.

  7. Sodium houttuyfonate inhibits biofilm formation and alginate biosynthesis-associated gene expression in a clinical strain of Pseudomonas aeruginosa in vitro

    PubMed Central

    WU, DA-QIANG; CHENG, HUIJUAN; DUAN, QIANGJUN; HUANG, WEIFENG

    2015-01-01

    The increasing multidrug resistance of Pseudomonas aeruginosa has become a serious public-health problem. In the present study, the inhibitory activities of sodium houttuyfonate (SH) against biofilm formation and alginate production in a clinical strain of P. aeruginosa (AH16) were investigated in vitro using crystal violet dying and standard curve methods, respectively. The cellular morphology of P. aeruginosa treated with SH was observed using a scanning electron microscope. Furthermore, reverse transcription-quantitative polymerase chain reaction was used to identify differences in the expression levels of genes associated with alginate biosynthesis as a result of the SH treatment. The results indicated that SH significantly inhibited biofilm formation, and decreased the levels of the primary biofilm constituent, alginate, in P. aeruginosa AH16 at various stages of biofilm development. In addition, scanning electron microscopy observations demonstrated that SH markedly altered the cellular morphology and biofilm structure of P. aeruginosa. Furthermore, the results from the reverse transcription-quantitative polymerase chain reaction analysis indicated that SH inhibited biofilm formation by mitigating the expression of the algD and algR genes, which are associated with alginate biosynthesis. Therefore, the present study has provided novel insights into the potent effects and underlying mechanisms of SH-induced inhibition of biofilm formation in a clinical strain of P. aeruginosa. PMID:26622388

  8. Sodium houttuyfonate inhibits biofilm formation and alginate biosynthesis-associated gene expression in a clinical strain of Pseudomonas aeruginosa in vitro.

    PubMed

    Wu, DA-Qiang; Cheng, Huijuan; Duan, Qiangjun; Huang, Weifeng

    2015-08-01

    The increasing multidrug resistance of Pseudomonas aeruginosa has become a serious public-health problem. In the present study, the inhibitory activities of sodium houttuyfonate (SH) against biofilm formation and alginate production in a clinical strain of P.aeruginosa (AH16) were investigated in vitro using crystal violet dying and standard curve methods, respectively. The cellular morphology of P. aeruginosa treated with SH was observed using a scanning electron microscope. Furthermore, reverse transcription-quantitative polymerase chain reaction was used to identify differences in the expression levels of genes associated with alginate biosynthesis as a result of the SH treatment. The results indicated that SH significantly inhibited biofilm formation, and decreased the levels of the primary biofilm constituent, alginate, in P. aeruginosa AH16 at various stages of biofilm development. In addition, scanning electron microscopy observations demonstrated that SH markedly altered the cellular morphology and biofilm structure of P. aeruginosa. Furthermore, the results from the reverse transcription-quantitative polymerase chain reaction analysis indicated that SH inhibited biofilm formation by mitigating the expression of the algD and algR genes, which are associated with alginate biosynthesis. Therefore, the present study has provided novel insights into the potent effects and underlying mechanisms of SH-induced inhibition of biofilm formation in a clinical strain of P. aeruginosa.

  9. Inhibition of sodium-linked glucose reabsorption normalizes diabetes-induced glomerular hyperfiltration in conscious adenosine A₁-receptor deficient mice.

    PubMed

    Sällström, J; Eriksson, T; Fredholm, B B; Persson, A E G; Palm, F

    2014-02-01

    Glomerular hyperfiltration is commonly observed in diabetics early after the onset of the disease and predicts the progression of nephropathy. Sustained hyperglycaemia is also closely associated with kidney hypertrophy and increased electrolyte and glucose reabsorption in the proximal tubule. In this study, we investigated the role of the increased tubular sodium/glucose cotransport for diabetes-induced glomerular hyperfiltration. To eliminate any potential confounding effect of the tubuloglomerular feedback (TGF) mechanism, we used adenosine A₁-receptor deficient (A1AR(-/-)) mice known to lack a functional TGF mechanism and compared the results to corresponding wild-type animals (A1AR(+/+)). Diabetes was induced by an intravenous bolus injection of alloxan. Glomerular filtration rate (GFR) was determined in conscious mice by a single bolus injection of inulin. The sodium/glucose cotransporters were inhibited by phlorizin 30 min prior to GFR measurements. Normoglycaemic animals had a similar GFR independent of genotype (A₁AR(+/+) 233 ± 11 vs. A₁AR(-/-) 241 ± 25 μL min(-1)), and induction of diabetes resulted in glomerular hyperfiltration in both groups (A₁AR(+/+) 380 ± 25 vs. A₁AR(-/-) 336 ± 35 μL min(-1); both P < 0.05). Phlorizin had no effect on GFR in normoglycaemic mice, whereas it reduced GFR in both genotypes during diabetes (A₁AR(+/+) 365 ± 18 to 295 ± 19, A₁AR(-/-) 354 ± 38 to 199 ± 15 μL min(-1); both P < 0.05). Notably, the reduction was more pronounced in the A₁AR(-/-) (P < 0.05). This study demonstrates that increased tubular sodium/glucose reabsorption is important for diabetes-induced hyperfiltration, and that the TGF mechanism is not involved in these alterations, but rather functions to reduce any deviations from a new set-point. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  10. Primary Biliary Acids Inhibit Hepatitis D Virus (HDV) Entry into Human Hepatoma Cells Expressing the Sodium-Taurocholate Cotransporting Polypeptide (NTCP)

    PubMed Central

    Veloso Alves Pereira, Isabel; Buchmann, Bettina; Sandmann, Lisa; Sprinzl, Kathrin; Schlaphoff, Verena; Döhner, Katinka; Vondran, Florian; Sarrazin, Christoph; Manns, Michael P.; Pinto Marques Souza de Oliveira, Cláudia; Sodeik, Beate; Ciesek, Sandra; von Hahn, Thomas

    2015-01-01

    Background The sodium-taurocholate cotransporting polypeptide (NTCP) is both a key bile acid (BA) transporter mediating uptake of BA into hepatocytes and an essential receptor for hepatitis B virus (HBV) and hepatitis D virus (HDV). In this study we aimed to characterize to what extent and through what mechanism BA affect HDV cell entry. Methods HuH-7 cells stably expressing NTCP (HuH-7/NTCP) and primary human hepatocytes (PHH) were infected with in vitro generated HDV particles. Infectivity in the absence or presence of compounds was assessed using immunofluorescence staining for HDV antigen, standard 50% tissue culture infectious dose (TCID50) assays and quantitative PCR. Results Addition of primary conjugated and unconjugated BA resulted in a dose dependent reduction in the number of infected cells while secondary, tertiary and synthetic BA had a lesser effect. This effect was observed both in HuH-7/NTCP and in PHH. Other replication cycle steps such as replication and particle assembly and release were unaffected. Moreover, inhibitory BA competed with a fragment from the large HBV envelope protein for binding to NTCP-expressing cells. Conversely, the sodium/BA-cotransporter function of NTCP seemed not to be required for HDV infection since infection was similar in the presence or absence of a sodium gradient across the plasma membrane. When chenodeoxycolic acid (15 mg per kg body weight) was administered to three chronically HDV infected individuals over a period of up to 16 days there was no change in serum HDV RNA. Conclusions Primary BA inhibit NTCP-mediated HDV entry into hepatocytes suggesting that modulation of the BA pool may affect HDV infection of hepatocytes. PMID:25646622

  11. [Pollution characteristics of antimony, arsenic and mercury in human hair at Xikuangshan antimony mining area and Guiyang City, China].

    PubMed

    Liu, Bi-Jun; Wu, Feng-Chang; Deng, Qiu-Jing; Mo, Chang-Li; Zhu, Jing; Zeng, Li; Fu, Zhi-You; Li, Wen

    2009-03-15

    The concentration levels of antimony, arsenic and mercury in human hair collected from Xikuangshan antimony mining area and Guiyang City were determined by hydride generation-atomic fluorescence spectrometry after having been digested by nitric acid and perchloric acid. The contents of Sb, As and Hg are 15.9, 4.21, 1.79 microg/g in the samples from Xikuangshan antimony mining area and 0.532, 0.280, 0.338 microg/g in the samples from Guiyang City respectively. The contents of Sb, As and Hg in human hair of Xikuangshan antimony area are much higher than those of Guiyang City. The independent-samples t-test shows that there are no marked differences in the contents of Sb and As between male and female hair samples from both Xikuangshan antimony mining area and Guiyang City (p > 0.05), while Hg contents in male hair are apparently higher than those in female hair from Guiyang City (p < or = 0.05). There is positive correlation observed between As and Sb, as well as between As and Hg, while Sb is weakly correlated with Hg (p < or = 0.01). These results show that the heavy metals (Sb, As and Hg) in antimony mining area may significantly affect human health than in the un-mining areas.

  12. Cloud point extraction combined with electrothermal atomic absorption spectrometry for the speciation of antimony(III) and antimony(V) in food packaging materials.

    PubMed

    Jiang, Xiuming; Wen, Shengping; Xiang, Guoqiang

    2010-03-15

    A simple, sensitive method for the speciation of inorganic antimony by cloud point extraction combined with electrothermal atomic absorption spectrometry (ETAAS) is presented and evaluated. The method based on the fact that formation of a hydrophobic complex of antimony(III) with ammonium pyrrolidine dithiocarbamate (APDC) at pH 5.0 and subsequently the hydrophobic complex enter into surfactant-rich phase, whereas antimony(V) remained in aqueous solutions. Antimony(III) in surfactant-rich phase was analyzed by ETAAS after dilution by 0.2 mL nitric acid in methanol (0.1M), and antimony(V) was calculated by subtracting antimony(III) from the total antimony after reducing antimony(V) to antimony(III) by l-cysteine. The main factors affecting the cloud point extraction, such as pH, concentration of APDC and Triton X-114, equilibrium temperature and incubation time, sample volume were investigated in detail. Under the optimum conditions, the detection limit (3 sigma) of the proposed method was 0.02 ng mL(-1) for antimony(III), and the relative standard deviation was 7.8% (c=1.0 ng mL(-1), n=7). The proposed method was successfully applied to speciation of inorganic antimony in the leaching solutions of different food packaging materials with satisfactory results. (c) 2009 Elsevier B.V. All rights reserved.

  13. Inhibition of cystathionine β-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation

    PubMed Central

    Yan, Jun; Hu, Shufen; Zou, Kang; Xu, Min; Wang, Qianliang; Miao, Xiuhua; Yu, Shan Ping; Xu, Guang-Yin

    2016-01-01

    The pathogenesis of pain in lumbar disc herniation (LDH) remains poorly understood. We have recently demonstrated that voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons were sensitized in a rat model of LDH. However, the detailed molecular mechanism for sensitization of VGSCs remains largely unknown. This study was designed to examine roles of the endogenous hydrogen sulfide synthesizing enzyme cystathionine β-synthetase (CBS) in sensitization of VGSCs in a previously validated rat model of LDH. Here we showed that inhibition of CBS activity by O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA) significantly attenuated pain hypersensitivity in LDH rats. Administration of AOAA also reduced neuronal hyperexcitability, suppressed the sodium current density, and right-shifted the V1/2 of the inactivation curve, of hindpaw innervating DRG neurons, which is retrogradely labeled by DiI. In vitro incubation of AOAA did not alter the excitability of acutely isolated DRG neurons. Furthermore, CBS was colocalized with NaV1.7 and NaV1.8 in hindpaw-innervating DRG neurons. Treatment of AOAA markedly suppressed expression of NaV1.7 and NaV1.8 in DRGs of LDH rats. These data suggest that targeting the CBS-H2S signaling at the DRG level might represent a novel therapeutic strategy for chronic pain relief in patients with LDH. PMID:27905525

  14. Antioxidant activity and inhibition of aflatoxin B1-, nifuroxazide-, and sodium azide-induced mutagenicity by extracts from Rhamnus alaternus L.

    PubMed

    Ammar, Rebai Ben; Sghaier, Mohamed Ben; Boubaker, Jihed; Bhouri, Wissem; Naffeti, Aicha; Skandrani, Ines; Bouhlel, Ines; Kilani, Soumaya; Ghedira, Kamel; Chekir-Ghedira, Leila

    2008-07-10

    The effect of extracts obtained from Rhamnus alaternus L. leaves on genotoxicity and SOS response induced by aflatoxin B(1) (10 microg/assay) as well as nifuroxazide (20 microg/assay) was investigated in a bacterial assay system, i.e., the SOS chromotest with Escherichia coli PQ37. The evaluation of the mutagenic and antimutagenic actions of the same extracts against the sodium azide (1.5 microg/plate)-induced mutagenicity was assayed using the Salmonella typhimurium assay system. The R. alaternus tested extracts exhibited no genotoxicity either with or without the external S9 activation mixture. However, all the extracts, particularly aqueous extract (A) and its chloroformic fraction (A(2)) significantly decreased the genotoxicity induced by aflatoxin B(1) and nifuroxazide. Moreover, the different extracts showed no mutagenicity when tested with Salmonella typhimurium strains TA1535 and TA1538 either with or without the S9 mix. Aqueous extract as well as its A(2) fraction exhibited the highest level of protection towards the direct mutagen, sodium azide-induced response in TA1535 strain with mutagenicity inhibition percentages of 83.6% and 91.4%, respectively, at a dose of 250 microg/plate. The results obtained by the Ames test assay confirm those of SOS chromotest. These same active extracts exhibited high xanthine oxidase (XOD) inhibiting with respective IC(50) values of 208 and 137 microg/ml, and superoxide anion-scavenging effects (IC(50) values of 132 and 117 microg/ml) when tested in the XOD enzymatic assay system. Our findings emphasize the potential of R. alaternus to prevent mutations and also its antioxidant effect.

  15. Astragalus polysaccharides protect against dextran sulfate sodium-induced colitis by inhibiting NF-κВ activation.

    PubMed

    Lv, Jun; Zhang, Yahong; Tian, Zhiqiang; Liu, Fang; Shi, Ying; Liu, Yao; Xia, Peiyuan

    2017-05-01

    Astragalus polysaccharide (APS) is a bioactive extract of Astragalus membranaceus (AM), which possess a wide range of medicinal benefits, including anti-inflammatory, anti-oxidative, anti-tumor and anti-diabetic effects. The present work evaluated the therapeutic effect of APS and its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)-induced colitis. The APS treatment led to significant improvements in colitis disease activity index (DAI) and histological scores, as well as significantly increased weight and colon length in mice as compared to the control group. Mechanically, reduced NF-κВ DNA phosphorylation activity and downregulated TNF-α, IL-1β, IL-6, IL-17 expressions and myeloperoxidase (MPO) activity were associated with improvement in colitis observed in APS-treated mice. These findings suggest that APS may represent a natural therapeutic approach for treating inflammatory bowel disease, such as ulcerative colitis.

  16. Effect of additives on Hg2+ reduction and precipitation inhibited by sodium dithiocarbamate in simulated flue gas desulfurization solutions.

    PubMed

    Lu, Rongjie; Hou, Jiaai; Xu, Jiang; Tang, Tingmei; Xu, Xinhua

    2011-11-30

    Mercury (II) (Hg(2+)) ion can be reduced by aqueous S(IV) (sulfite and/or bisulfite) species, which leads to elemental mercury (Hg(0)) emissions in wet flue gas desulfurization (FGD) systems. Numerous reports have demonstrated the high trapping efficiency of sodium dithiocarbamate over heavy metals. In this paper, a novel sodium dithiocarbamate, DTCR, was utilized as a precipitator to control Hg(2+) reduction and Hg(0) emission against S(IV) in FGD solutions. Results indicated that Hg(2+) reduction efficiency decreased dramatically while precipitation rate peaked at around 91.0% in consistence with the increment of DTCR dosage. Initial pH and temperature had great inhibitory effects on Hg(2+) reduction: the Hg(2+) removal rate gradually increased and reached a plateau along with the increment of temperature and initial pH value. Chloride played a key role in Hg(2+) reduction and precipitation reactions. When Cl(-) concentration increased from 0 to 150 mM, Hg(2+) removal rate dropped from 93.84% to 86.05%, and the Hg(2+) reduction rate remained at a low level (<7.8%). SO(4)(2-), NO(3)(-) and other common metal ions would affect the efficiency of Hg(2+) reduction and precipitation reactions in the simulated desulfurization solutions: Hg(2+) removal rate could always be above 90%, while Hg(2+) reduction rate was maintained at below 10%. The predominance of DTCR over aqueous S(IV), indicated by the results above, has wide industrial applications in FGD systems.

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

    PubMed

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

    2016-04-15

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

  18. Sodium orthovanadate associated with pharmacological doses of ascorbate causes an increased generation of ROS in tumor cells that inhibits proliferation and triggers apoptosis.

    PubMed

    Günther, Tânia Mara Fischer; Kviecinski, Maicon Roberto; Baron, Carla Cristine; Felipe, Karina Bettega; Farias, Mirelle Sifroni; da Silva, Fabiana Ourique; Bücker, Nádia Cristina Falcão; Pich, Claus Tröger; Ferreira, Eduardo Antonio; Wilhelm Filho, Danilo; Verrax, Julien; Calderon, Pedro Buc; Pedrosa, Rozangela Curi

    2013-01-18

    Pharmacological doses of ascorbate were evaluated for its ability to potentiate the toxicity of sodium orthovanadate (Na(3)VO(4)) in tumor cells. Cytotoxicity, inhibition of cell proliferation, generation of ROS and DNA fragmentation were assessed in T24 cells. Na(3)VO(4) was cytotoxic against T24 cells (EC(50)=5.8 μM at 24 h), but in the presence of ascorbate (100 μM) the EC(50) fell to 3.3 μM. Na(3)VO(4) plus ascorbate caused a strong inhibition of cell proliferation (up to 20%) and increased the generation of ROS (4-fold). Na(3)VO(4) did not directly cleave plasmid DNA, at this aspect no synergism was found occurring between Na(3)VO(4) and ascorbate once the resulting action of the combination was no greater than that of both substances administered separately. Cells from Ehrlich ascites carcinoma-bearing mice were used to determine the activity of antioxidant enzymes, the extent of the oxidative damage and the type of cell death. Na(3)VO(4) alone, or combined with ascorbate, increased catalase activity, but only Na(3)VO(4) plus ascorbate increased superoxide dismutase activity (up to 4-fold). Oxidative damage on proteins and lipids was higher due to the treatment done with Na(3)VO(4) plus ascorbate (2-3-fold). Ascorbate potentiated apoptosis in tumor cells from mice treated with Na(3)VO(4). The results indicate that pharmacological doses of ascorbate enhance the generation of ROS induced by Na(3)VO(4) in tumor cells causing inhibition of proliferation and apoptosis. Apoptosis induced by orthovanadate and ascorbate is closer related to inhibition on Bcl-xL and activation of Bax. Our data apparently rule out a mechanism of cell demise p53-dependent or related to Cdk2 impairment. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Mechanism of sodium uptake in PNA negative MR cells from rainbow trout, Oncorhynchus mykiss as revealed by silver and copper inhibition.

    PubMed

    Goss, Greg; Gilmour, Kathleen; Hawkings, Guy; Brumbach, Jonathan H; Huynh, Maily; Galvez, Fernando

    2011-07-01

    The rate of acid-stimulated and phenamil-sensitive sodium (Na(+)) uptake was measured in three different cell lineages: pavement cells (PVC), total mitochondrion-rich (MR) cell populations, and peanut lectin agglutinin-negative mitochondrion-rich cells (PNA(-) MR) isolated from the rainbow trout gill epithelium. Despite the presence of basal levels of Na(+) uptake in PVC, this transport was not enhanced by acidification, nor was it inhibited by independent treatment with bafilomycin (i.e., a V-type H(+)-ATPase inhibitor), phenamil (i.e., a specific inhibitor of ENaC), or Ag (a specific inhibitor of active Na(+) transport in fish). In contrast, Na(+) uptake in PNA(-) MR cells was increased by ~220% above basal levels following acidification of near 0.4 pH units in the presence of 1.0 mM external Na(+). Acid-stimulated Na(+) transport was entirely inhibited by both phenamil and bafilomycin. Silver (Ag) and copper (Cu), which are known to interfere with active Na(+) transport in fish, were also responsible for inhibiting acid stimulated Na(+) uptake in PNA(-) MR cells, but by themselves had no effect on basal Na(+) transport. Thus, we demonstrate that Ag specifically prevented acid-stimulated Na(+) uptake in PNA(-) MR cells in a dose-dependent manner. We also demonstrate rapid (<1 min) and significant inhibition of carbonic anhydrase (CA) by Ag in PNA(-) MR cells, but not in PVC. These data lend further support to the idea of a PNA(-) MR cell type as the primary site for Na(+) uptake in the freshwater (FW) gill phenotype of rainbow trout. Moreover, these findings provide support for the importance of intracellular protons in regulating the movement of Na(+) across the apical surface of the fish gill.

  20. Ginsenoside Metabolite Compound K Promotes Recovery of Dextran Sulfate Sodium-Induced Colitis and Inhibits Inflammatory Responses by Suppressing NF-κB Activation

    PubMed Central

    Li, Juan; Zhong, Wei; Wang, Weiwei; Hu, Shaoping; Yuan, Jiahui; Zhang, Bing; Hu, Tianhui; Song, Gang

    2014-01-01

    Phytogenic compounds with anti-oxidant and anti-inflammatory properties, such as ginsenoside metabolite compound K (CK) or berberine (BBR), are currently discussed as promising complementary agents in the prevention and treatment of cancer and inflammation. The latest study showed that ginsenoside Rb1 and its metabolites could inhibit TNBS-induced colitis injury. However, the functional mechanisms of anti-inflammation effects of ginsenoside, particularly its metabolite CK are still not clear. Here, using dextran sulfate sodium (DSS)-induced colitis in mice, clinical parameters, intestinal integrity, pro-inflammatory cytokines production, and signaling pathways in colonic tissues were determined. In mild and sever colitis mice, CK and BBR (as a positive agent) alleviated colitis histopathology injury, ameliorated myeloperoxidase (MPO) activity, reduced pro-inflammatory cytokines production, such as, IL-6, IL-1β, TNF-α, and increased anti-inflammatory cytokine IL-10 production in both mice colon tissues and blood. Nevertheless, the results revealed that CK and BBR inhibited NF-κB p65 nuclear translocation, downregulated p-IκBα and upregulated IκBα, indicating that CK, as well as BBR, suppressed the activation of the NF-κB pathway in the progression of colitis with immunofluorescence, immunohistochemical and western blotting analysis. Furthermore, CK inhibited pro-inflammatory cytokines production in LPS-activated macrophages via down-regulation of NF-κB signaling pathway. Taken together, our results not only reveal that CK promotes the recovery of the progression of colitis and inhibits the inflammatory responses by suppressing NF-κB activation, but also suggest that CK downregulates intestinal inflammation through regulating the activation of macrophages and pro-inflammatory cytokines production. PMID:24504372

  1. Local-anesthetic like inhibition of the cardiac sodium channel Nav1.5 α-subunit by 5-HT3 receptor antagonists.

    PubMed

    Van't Klooster, Mariet P; Foadi, Nilufar; Hage, Axel; Stoetzer, Carsten; Wegner, Florian; Eberhardt, Mirjam; Leffler, Andreas

    2016-10-15

    5-hydroxytryptamine 3 receptor (5-HT3 receptor) antagonists are administered for prevention and therapy of nausea and vomiting. Although regarded as safe therapeutics, they can also provoke arrhythmias by prolonging the QRS interval. However, the mechanisms mediating this cardiotoxicity are poorly understood. Here we investigated effects of 5-HT3 receptor antagonists on the cardiac Na(+) channel Nav1.5. We explored the interaction of dolasetron, tropisetron, granisetron and ondansetron on the human α-subunit Nav1.5 heterologously expressed in HEK293 cells. Sodium currents were explored by means of whole-cell patch clamp recordings. All four substances inhibited the Nav1.5 in a concentration and state-dependent manner. Dolasetron displayed the lowest blocking efficacy, and tropisetron was the most potent blocker with a half maximum blocking concentration of 18µM for tonic block of inactivated channels. Tropisetron was also the most potent use-dependent inhibitor, and it also induced a strong open -channel block. Both tonic and use-dependent block by tropisetron were abbreviated on the local-anesthetic insensitive mutant Nav1.5-F1760A. Co-administration of tropisetron and the local anesthetic bupivacaine or the hypnotic propofol augmented inhibition of Nav1.5. Our data demonstrate that 5-HT3 receptor antagonists induce a local-anesthetic like inhibition of Nav1.5, and that they display different blocking efficacies. Reports on a relevant cardiotoxicity of dolasetron as opposed to other 5-HT3 receptor antagonists do not seem to correlate with a block of Nav1.5. As inhibition of Nav1.5 was enhanced by propofol and bupivacaine however, it is possible that a combined administration of Na(+) channel blockers and 5-HT3 receptor antagonists can provoke arrhythmias.

  2. Anti-diabetic and anti-obesity agent sodium tungstate enhances GCN pathway activation through Glc7p inhibition.

    PubMed

    Rodriguez-Hernandez, C J; Guinovart, J J; Murguia, J R

    2012-02-03

    Tungstate counteracts diabetes and obesity in animal models, but its molecular mechanisms remain elusive. Our Saccharomyces cerevisiae-based approach has found that tungstate alleviated the growth defect induced by nutrient stress and enhanced the activation of the GCN pathway. Tungstate relieved the sensitivity to starvation of a gcn2-507 yeast hypomorphic mutant, indicating that tungstate modulated the GCN pathway downstream of Gcn2p. Interestingly, tungstate inhibited Glc7p and PP1 phosphatase activity, both negative regulators of the GCN pathway in yeast and humans, respectively. Accordingly, overexpression of a dominant-negative Glc7p mutant in yeast mimicked tungstate effects. Therefore tungstate alleviates nutrient stress in yeast by in vivo inhibition of Glc7p. These data uncover a potential role for tungstate in the treatment of PP1 and GCN related diseases.

  3. Marked increases in mucociliary clearance produced by synergistic secretory agonists or inhibition of the epithelial sodium channel

    PubMed Central

    Joo, Nam Soo; Jeong, Jin Hyeok; Cho, Hyung-Ju; Wine, Jeffrey J.

    2016-01-01

    Mucociliary clearance (MCC) is a critical host innate defense mechanism in airways, and it is impaired in cystic fibrosis (CF) and other obstructive lung diseases. Epithelial fluid secretion and absorption modify MCC velocity (MCCV). We tested the hypotheses that inhibiting fluid absorption accelerates MCCV, whereas inhibiting fluid secretion decelerates it. In airways, ENaC is mainly responsible for fluid absorption, while anion channels, including CFTR and Ca2+-activated chloride channels mediate anion/fluid secretion. MCCV was increased by the cAMP-elevating agonists, forskolin or isoproterenol (10 μM) and by the Ca2+-elevating agonist, carbachol (0.3 μM). The CFTR-selective inhibitor, CFTRinh-172, modestly reduced MCCV-increases induced by forskolin or isoproterenol but not increases induced by carbachol. The ENaC inhibitor benzamil increased basal MCCV as well as MCCV increases produced by forskolin or carbachol. MCC velocity was most dramatically accelerated by the synergistic combination of forskolin and carbachol, which produced near-maximal clearance rates regardless of prior treatment with CFTR or ENaC inhibitors. In CF airways, where CFTR-mediated secretion (and possibly synergistic MCC) is lost, ENaC inhibition via exogenous agents may provide therapeutic benefit, as has long been proposed. PMID:27830759

  4. Effects of antimony on the electrochemical behaviour of lead dioxide in sulphuric acid

    NASA Astrophysics Data System (ADS)

    Boggio, A.; Maja, M.; Penazzi, N.

    The effect of antimony on the reduction of the two allotropic forms of lead dioxide in sulphuric acid electrolyte has been studied. The effects of antimony doping of the lead dioxide lattice and the effects of antimony contamination of the electrolyte have been considered separately. In the first case antimony increases the quantity of charge related to the reduction, and in the second it exerts a strong passivating influence on the lead dioxide electrodes.

  5. Role of Efflux Pumps and Intracellular Thiols in Natural Antimony Resistant Isolates of Leishmania donovani

    PubMed Central

    Rai, Smita; Bhaskar; Goel, Sudhir K.; Nath Dwivedi, Upendra; Sundar, Shyam; Goyal, Neena

    2013-01-01

    Background In view of the recent upsurge in the phenomenon of therapeutic failure, drug resistance in Leishmania, developed under natural field conditions, has become a great concern yet little understood. Accordingly, the study of determinants of antimony resistance is urgently warranted. Efflux transporters have been reported in Leishmania but their role in clinical resistance is still unknown. The present study was designed to elucidate the mechanism of natural antimony resistance in L. donovani field isolates by analyzing the functionality of efflux pump(s) and expression profiles of known genes involved in transport and thiol based redox metabolism Methodology/Principal Findings We selected 7 clinical isolates (2 sensitive and 5 resistant) in addition to laboratory sensitive reference and SbIII resistant mutant strains for the present study. Functional characterization using flow cytometry identified efflux pumps that transported substrates of both P-gp and MRPA and were inhibited by the calmodulin antagonist trifluoperazine. For the first time, verapamil sensitive efflux pumps for rhodamine 123 were observed in L. donovani that were differentially active in resistant isolates. RT-PCR confirmed the over-expression of MRPA in isolates with high resistance index only. Resistant isolates also exhibited consistent down regulation of AQP1 and elevated intracellular thiol levels which were accompanied with increased expression of ODC and TR genes. Interestingly, γ-GCS is not implicated in clinical resistance in L. donovani isolates. Conclusions/Significance Here we demonstrate for the first time, the role of P-gp type plasma membrane efflux transporter(s) in antimony resistance in L. donovani field isolates. Further, decreased levels of AQP1 and elevated thiols levels have emerged as biomarkers for clinical resistance. PMID:24069359

  6. Mitochondrial inhibitor sodium azide inhibits the reorganization of mitochondria-rich cytoplasm and the establishment of the anteroposterior axis in ascidian embryo.

    PubMed

    Ishii, Hirokazu; Shirai, Takuma; Makino, Chisato; Nishikata, Takahito

    2014-02-01

    In ascidian eggs, cytoplasmic and cortical reorganization, previously called ooplasmic segregation, occurs in two phases during the first cell cycle. In the second phase of reorganization, the mitochondria-rich cytoplasm (myoplasm) moves to the future posterior side, concurrent with sperm aster migration along the egg cortex. Although this reorganization is the critical step for establishing the anteroposterior axis, its molecular mechanism is not fully understood. In this study, we showed that low concentrations of the mitochondrial inhibitor sodium azide (NaN3 ), which showed the low toxicity in sperm, inhibited the second phase of reorganization without the microtubule depolymerization. In the NaN3 -treated embryo, the sperm aster was not attracted to the cortex and altered its migration pathway; therefore, the myoplasm remained at the vegetal pole. Consequently, the anteroposterior axis was not established. Another mitochondrial inhibitor, oligomycin, did not affect these processes. These results suggest that NaN3 inhibits unknown molecules that are important for the second phase of reorganization. Identifying the target molecule of NaN3 will lead to a molecular understanding of cytoplasmic and cortical reorganization.

  7. Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2.

    PubMed

    Miao, Wei; Wu, Xiujuan; Wang, Kang; Wang, Wenjing; Wang, Yumei; Li, Zhigang; Liu, Jingjing; Li, Li; Peng, Luying

    2016-10-10

    As a physiological small molecular product from the microbial fermentation of dietary fibers, butyrate plays an important role in maintaining intestinal health. Our previous works have proved that the effect of sodium butyrate (NaB) on the intestinal barrier function is mediated by activation of AMP-activated protein kinase (AMPK). However, the detailed pathway involved remains unknown. Using the calcium switch assay in the Caco-2 cell monolayer model, we found here that NaB activated AMPK mainly by increasing the calcium level, but not the ATP concentration, via promoting store-operated calcium entry (SOCE). Upon the activation of AMPK, NaB promoted the reassembly of tight junctions (TJs) based on reducing the phosphorylation of myosin II regulatory light chain (MLC2) at Ser19 and increasing phosphorylation of protein kinase C β2 (PKCβ2) at Ser660. Inhibiting (protein kinase C β) PKCβ blocked the reassembly of TJs induced by NaB in the barrier monolayer model. These results indicated that NaB could activate the calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) pathway to mediate AMPK phosphorylating, which then inhibited the phosphorylation of MLC2 and promoted the phosphorylation of PKCβ2, respectively, so that the downstream molecules of AMPK coordinately contributed to the reassembly of TJs in the Caco-2 barrier model. These results suggested a potential mechanism of butyrate for intestine homeostasis and protection.

  8. Phlomis mauritanica extracts reduce the xanthine oxidase activity, scavenge the superoxide anions, and inhibit the aflatoxin B1-, sodium azide-, and 4-nitrophenyldiamine-induced mutagenicity in bacteria.

    PubMed

    Limem, Ilef; Bouhlel, Ines; Bouchemi, Meriem; Kilani, Soumaya; Boubaker, Jihed; Ben-Sghaier, Mohamed; Skandrani, Ines; Behouri, Wissem; Neffati, Aicha; Ghedira, Kamel; Chekir-Ghedira, Leila

    2010-06-01

    Four extracts were prepared from the leaves of Phlomis mauritanica: lyophilized infusion, total oligomer flavonoids, methanol, and ethyl acetate extracts. The antimutagenic properties of these extracts were investigated by assessing the inhibition of the mutagenic effects of direct-acting mutagens such as sodium azide and 4-nitrophenylenediamine and indirect-acting mutagens like aflatoxin B1 (AFB1) using the Ames assay. The four extracts prepared from P. mauritanica strongly inhibit the mutagenicity induced by AFB1 in both Salmonella typhimurium TA 100 and TA 98 assay systems. Lyophilized infusion and methanol extracts at the dose of 250 microg per plate reduced AFB1 mutagenicity by 93% and 91%, respectively, in S. typhymurium strain TA 100. We examined also the antioxidant effect of these extracts by the enzymatic xanthine/xanthine oxidase assay. Result indicated that total oligomer flavonoids and ethyl acetate and methanol extracts were potent inhibitors of xanthine oxidase activity. In contrast, lyophilized infusion, total oligomer flavonoids, and methanol extracts exhibited a high degree of superoxide anion scavenging. Our findings emphasize the potential of P. mauritanica extracts to prevent mutations and oxidant effects. Furthermore, the results presented here could be an additional argument to support the use of this species as a medicinal and dietary plant.

  9. Sodium houttuyfonate, a potential phytoanticipin derivative of antibacterial agent, inhibits bacterial attachment and pyocyanine secretion of Pseudomonas aeruginosa by attenuating flagella-mediated swimming motility.

    PubMed

    Shao, Jing; Cheng, Huijuan; Wang, Changzhong; Wu, Daqiang; Zhu, Xiaoli; Zhu, Lingling; Sun, Zhenxin

    2013-12-01

    Pseudomonas aeruginosa is a well-known clinical pathogen for its recalcitrant infection caused by biofilm formation which are initiated by flagella-mediated attachment. Sodium houttuyfonate (SH) is a natural phytoanticipin derivative of houttuynin and has anti-pathogenic effect on P. aeruginosa biofilm formation. In this paper, when using 1/2 × MIC SH, the diameter of P. aeruginosa swimming motility was sharply shortened to 36 % in 24 h incubation, and the fold changes of fliC required for swimming motility was 0.36 in 24 h cultivation, the adherence inhibition accounted for about 46 %, and the pyocyanin production decreased to 47 % after 1-day treatment and 56 % after 3-day treatment with obvious visual changes from dark green to light green, compared with the negative control. With the help of mass spectra and scanning electronic microscope, 1/2 × MIC SH was further testified to be enough to eradicate flagella and inhibit pyocyanin secretion of P. aeruginosa. The results do not only re-affirm the close interplay of attachment and virulence (i.e. swimming motility and pyocyanin), but also unravel the potential mechanism of SH on anti-biofilm of P. aeruginosa.

  10. Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2

    PubMed Central

    Miao, Wei; Wu, Xiujuan; Wang, Kang; Wang, Wenjing; Wang, Yumei; Li, Zhigang; Liu, Jingjing; Li, Li; Peng, Luying

    2016-01-01

    As a physiological small molecular product from the microbial fermentation of dietary fibers, butyrate plays an important role in maintaining intestinal health. Our previous works have proved that the effect of sodium butyrate (NaB) on the intestinal barrier function is mediated by activation of AMP-activated protein kinase (AMPK). However, the detailed pathway involved remains unknown. Using the calcium switch assay in the Caco-2 cell monolayer model, we found here that NaB activated AMPK mainly by increasing the calcium level, but not the ATP concentration, via promoting store-operated calcium entry (SOCE). Upon the activation of AMPK, NaB promoted the reassembly of tight junctions (TJs) based on reducing the phosphorylation of myosin II regulatory light chain (MLC2) at Ser19 and increasing phosphorylation of protein kinase C β2 (PKCβ2) at Ser660. Inhibiting (protein kinase C β) PKCβ blocked the reassembly of TJs induced by NaB in the barrier monolayer model. These results indicated that NaB could activate the calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) pathway to mediate AMPK phosphorylating, which then inhibited the phosphorylation of MLC2 and promoted the phosphorylation of PKCβ2, respectively, so that the downstream molecules of AMPK coordinately contributed to the reassembly of TJs in the Caco-2 barrier model. These results suggested a potential mechanism of butyrate for intestine homeostasis and protection. PMID:27735862

  11. Adding sodium dodecyl sulfate and Pseudomonas aeruginosa UG2 biosurfactants inhibits polycyclic aromatic hydrocarbon biodegradation in a weathered creosote-contaminated soil.

    PubMed

    Deschênes, L; Lafrance, P; Villeneuve, J P; Samson, R

    1996-12-01

    The effect of two anionic surfactants was assessed during biodegradation of 13 of the 16 USEPA priority polycyclic aromatic hydrocarbons (PAH) in a wood-preserving soil contaminated with creosote and pentacholorophenol for a period of at least 20 years. Sodium dodecyl sulfate (SDS) and biosurfactants from Pseudomonas aeruginosa UG2 were utilized at concentrations of 10, 100 and 500 micrograms/g soil. Because both surfactants are readily biodegradable, the microcosms received a fresh spike of surfactant every 2 weeks. Biodegradation of aged PAH residues was monitored by GC/MS for a period of 45 weeks. Results indicated that the biodegradation of the three-ring PAH was rapid and almost complete but was slowed by the addition of 100 micrograms/g and 500 micrograms/g chemical surfactant. Similarly, at the same concentrations, the two surfactants significantly decreased the biodegradation rate of the four-ring PAH. In this case, the inhibition was more pronounced with SDS. High-molecular-mass PAH (more than four rings) were not biodegraded under the test conditions. It was suggested that the preferential utilization of surfactants by PAH degraders was responsible for the inhibition observed in the biodegradation of the hydrocarbons. The high biodegradability and the inhibitory effect of these two surfactants would have a significant impact on the development of both above-ground and in situ site reclamation processes.

  12. Peptide-rich venom from the spider Heteropoda venatoria potently inhibits insect voltage-gated sodium channels.

    PubMed

    Huang, Yazhou; Wu, Xinzhou; Zhang, Peng; Duan, Zhigui; Zhou, Xi; Chen, Minzhi; Farooq, Athar; Liang, Songping; Liu, Zhonghua

    2017-01-01

    Heteropoda venatoria is a venomous spider species distributed worldwide and has a characteristic habit of feeding on insects. Reverse-phase high-performance liquid chromatography and matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry analyses revealed that H. venatoria venom contains hundreds of peptides with a predominant molecular weights of 3000-5000 Da. Intra-abdominal injection of the venom had severe toxic effects on cockroaches and caused death at higher concentrations. The LD50 was 28.18 μg/g of body weight in the cockroach. It was found that the venom had potent inhibitory effect on voltage-gated sodium channels (VGSCs) in Periplaneta americana cockroach dorsal unpaired median (DUM) neurons with an IC50 values of 6.25 ± 0.02 μg/mL. However, 100 μg/mL venom only partially blocked VGSC currents in rat dorsal root ganglion cells, a much lower inhibitory effect than that on DUM VGSCs. Our results indicate that the venom of H. venatoria contains diverse neurotoxins that might become new leads for bioinsecticides. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. [Antimony and other heavy metals in metallic kitchen ware].

    PubMed

    Ishiwata, H; Sugita, T; Yoshihira, K

    1989-01-01

    The antimony in metallic kitchen ware was determined. The content of this element in metals used for the production or repairing of utensils, containers and packaging which come in contact with foods is regulated and should be less than 5% in under the Japanese Food Sanitation Law. In eight metallic samples, antimony was detected in solder used for the production of a can for green tea and an eggbeater. The contents were 1.30% in the former and 1.90% in the latter. No antimony was detected in solder used for a cookie cutter. A sample of solder used for electric work, not for food utensils, contained 0.81% of antimony. In other metallic utensils which come in contact with food such as aluminum foil, a brass spoon, a stainless steel fork, a wire netting, and an iron rock for vegetable color stabilizing, antimony was not detected at a 0.05% detection limit. A qualitative test using rhodamine B also showed positive results in only three solder samples. Lead concentrations in solder used for the kitchen ware were from 39.3 to 51.3%. These concentrations were higher than the limit (20%) of lead content by the Law. No cadmium was detected in any samples.

  14. Proteomic and Genomic Analyses of Antimony Resistant Leishmania infantum Mutant

    PubMed Central

    Brotherton, Marie-Christine; Bourassa, Sylvie; Leprohon, Philippe; Légaré, Danielle; Poirier, Guy G.; Droit, Arnaud; Ouellette, Marc

    2013-01-01

    Background Antimonials remain the primary antileishmanial drugs in most developing countries. However, drug resistance to these compounds is increasing and our understanding of resistance mechanisms is partial. Methods/Principal Findings In the present study, quantitative proteomics using stable isotope labelling of amino acids in cell culture (SILAC) and genome next generation sequencing were used in order to better characterize in vitro generated Leishmania infantum antimony resistant mutant (Sb2000.1). Using the proteomic method, 58 proteins were found to be differentially regulated in Sb2000.1. The ABC transporter MRPA (ABCC3), a known marker of antimony resistance, was observed for the first time in a proteomic screen. Furthermore, transfection of its gene conferred antimony resistance in wild-type cells. Next generation sequencing revealed aneuploidy for 8 chromosomes in Sb2000.1. Moreover, specific amplified regions derived from chromosomes 17 and 23 were observed in Sb2000.1 and a single nucleotide polymorphism (SNP) was detected in a protein kinase (LinJ.33.1810-E629K). Conclusion/Significance Our results suggest that differentially expressed proteins, chromosome number variations (CNVs), specific gene amplification and SNPs are important features of antimony resistance in Leishmania. PMID:24312377

  15. Tarantula huwentoxin-IV inhibits neuronal sodium channels by binding to receptor site 4 and trapping the domain ii voltage sensor in the closed configuration.

    PubMed

    Xiao, Yucheng; Bingham, Jon-Paul; Zhu, Weiguo; Moczydlowski, Edward; Liang, Songping; Cummins, Theodore R

    2008-10-03

    Peptide toxins with high affinity, divergent pharmacological functions, and isoform-specific selectivity are powerful tools for investigating the structure-function relationships of voltage-gated sodium channels (VGSCs). Although a number of interesting inhibitors have been reported from tarantula venoms, little is known about the mechanism for their interaction with VGSCs. We show that huwentoxin-IV (HWTX-IV), a 35-residue peptide from tarantula Ornithoctonus huwena venom, preferentially inhibits neuronal VGSC subtypes rNav1.2, rNav1.3, and hNav1.7 compared with muscle subtypes rNav1.4 and hNav1.5. Of the five VGSCs examined, hNav1.7 was most sensitive to HWTX-IV (IC(50) approximately 26 nM). Following application of 1 microm HWTX-IV, hNav1.7 currents could only be elicited with extreme depolarizations (>+100 mV). Recovery of hNav1.7 channels from HWTX-IV inhibition could be induced by extreme depolarizations or moderate depolarizations lasting several minutes. Site-directed mutagenesis analysis indicated that the toxin docked at neurotoxin receptor site 4 located at the extracellular S3-S4 linker of domain II. Mutations E818Q and D816N in hNav1.7 decreased toxin affinity for hNav1.7 by approximately 300-fold, whereas the reverse mutations in rNav1.4 (N655D/Q657E) and the corresponding mutations in hNav1.5 (R812D/S814E) greatly increased the sensitivity of the muscle VGSCs to HWTX-IV. Our data identify a novel mechanism for sodium channel inhibition by tarantula toxins involving binding to neurotoxin receptor site 4. In contrast to scorpion beta-toxins that trap the IIS4 voltage sensor in an outward configuration, we propose that HWTX-IV traps the voltage sensor of domain II in the inward, closed configuration.

  16. Tarantula Huwentoxin-IV Inhibits Neuronal Sodium Channels by Binding to Receptor Site 4 and Trapping the Domain II Voltage Sensor in the Closed Configuration*S⃞

    PubMed Central

    Xiao, Yucheng; Bingham, Jon-Paul; Zhu, Weiguo; Moczydlowski, Edward; Liang, Songping; Cummins, Theodore R.

    2008-01-01

    Peptide toxins with high affinity, divergent pharmacological functions, and isoform-specific selectivity are powerful tools for investigating the structure-function relationships of voltage-gated sodium channels (VGSCs). Although a number of interesting inhibitors have been reported from tarantula venoms, little is known about the mechanism for their interaction with VGSCs. We show that huwentoxin-IV (HWTX-IV), a 35-residue peptide from tarantula Ornithoctonus huwena venom, preferentially inhibits neuronal VGSC subtypes rNav1.2, rNav1.3, and hNav1.7 compared with muscle subtypes rNav1.4 and hNav1.5. Of the five VGSCs examined, hNav1.7 was most sensitive to HWTX-IV (IC50 ∼ 26 nm). Following application of 1 μm HWTX-IV, hNav1.7 currents could only be elicited with extreme depolarizations (>+100 mV). Recovery of hNav1.7 channels from HWTX-IV inhibition could be induced by extreme depolarizations or moderate depolarizations lasting several minutes. Site-directed mutagenesis analysis indicated that the toxin docked at neurotoxin receptor site 4 located at the extracellular S3-S4 linker of domain II. Mutations E818Q and D816N in hNav1.7 decreased toxin affinity for hNav1.7 by ∼300-fold, whereas the reverse mutations in rNav1.4 (N655D/Q657E) and the corresponding mutations in hNav1.5 (R812D/S814E) greatly increased the sensitivity of the muscle VGSCs to HWTX-IV. Our data identify a novel mechanism for sodium channel inhibition by tarantula toxins involving binding to neurotoxin receptor site 4. In contrast to scorpion β-toxins that trap the IIS4 voltage sensor in an outward configuration, we propose that HWTX-IV traps the voltage sensor of domain II in the inward, closed configuration. PMID:18628201

  17. 40 CFR 440.90 - Applicability; description of the antimony ore subcategory.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... antimony ore subcategory. 440.90 Section 440.90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORE MINING AND DRESSING POINT SOURCE CATEGORY Antimony Ore Subcategory § 440.90 Applicability; description of the antimony ore subcategory. The provisions of this...

  18. 40 CFR 440.90 - Applicability; description of the antimony ore subcategory.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... antimony ore subcategory. 440.90 Section 440.90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS ORE MINING AND DRESSING POINT SOURCE CATEGORY Antimony Ore Subcategory § 440.90 Applicability; description of the antimony ore subcategory. The provisions of...

  19. Laser resonance ionization spectroscopy of antimony

    NASA Astrophysics Data System (ADS)

    Li, R.; Lassen, J.; Ruczkowski, J.; Teigelhöfer, A.; Bricault, P.

    2017-02-01

    The resonant ionization laser ion source is an element selective, efficient and versatile ion source to generate radioactive ion beams at on-line mass separator facilities. For some elements with complex atomic structures and incomplete spectroscopic data, laser spectroscopic investigations are required for ionization scheme development. Laser resonance ionization spectroscopy using Ti:Sa lasers has been performed on antimony (Sb) at TRIUMF's off-line laser ion source test stand. Laser light of 230.217 nm (vacuum wavelength) as the first excitation step and light from a frequency-doubled Nd:YVO4 laser (532 nm) as the nonresonant ionization step allowed to search for suitable second excitation steps by continuous wavelength scans from 720 nm to 920 nm across the wavelength tuning range of a grating-tuned Ti:Sa laser. Upon the identification of efficient SES, the third excitation steps for resonance ionization were investigated by laser scans across Rydberg states, the ionization potential and autoionizing states. One Rydberg state and six AI states were found to be well suitable for efficient resonance ionization.

  20. Potassium uptake supporting plant growth in the absence of AKT1 channel activity: Inhibition by ammonium and stimulation by sodium

    NASA Technical Reports Server (NTRS)

    Spalding, E. P.; Hirsch, R. E.; Lewis, D. R.; Qi, Z.; Sussman, M. R.; Lewis, B. D.

    1999-01-01

    A transferred-DNA insertion mutant of Arabidopsis that lacks AKT1 inward-rectifying K+ channel activity in root cells was obtained previously by a reverse-genetic strategy, enabling a dissection of the K+-uptake apparatus of the root into AKT1 and non-AKT1 components. Membrane potential measurements in root cells demonstrated that the AKT1 component of the wild-type K+ permeability was between 55 and 63% when external [K+] was between 10 and 1,000 microM, and NH4+ was absent. NH4+ specifically inhibited the non-AKT1 component, apparently by competing for K+ binding sites on the transporter(s). This inhibition by NH4+ had significant consequences for akt1 plants: K+ permeability, 86Rb+ fluxes into roots, seed germination, and seedling growth rate of the mutant were each similarly inhibited by NH4+. Wild-type plants were much more resistant to NH4+. Thus, AKT1 channels conduct the K+ influx necessary for the growth of Arabidopsis embryos and seedlings in conditions that block the non-AKT1 mechanism. In contrast to the effects of NH4+, Na+ and H+ significantly stimulated the non-AKT1 portion of the K+ permeability. Stimulation of akt1 growth rate by Na+, a predicted consequence of the previous result, was observed when external [K+] was 10 microM. Collectively, these results indicate that the AKT1 channel is an important component of the K+ uptake apparatus supporting growth, even in the "high-affinity" range of K+ concentrations. In the absence of AKT1 channel activity, an NH4+-sensitive, Na+/H+-stimulated mechanism can suffice.

  1. Potassium uptake supporting plant growth in the absence of AKT1 channel activity: Inhibition by ammonium and stimulation by sodium

    NASA Technical Reports Server (NTRS)

    Spalding, E. P.; Hirsch, R. E.; Lewis, D. R.; Qi, Z.; Sussman, M. R.; Lewis, B. D.

    1999-01-01

    A transferred-DNA insertion mutant of Arabidopsis that lacks AKT1 inward-rectifying K+ channel activity in root cells was obtained previously by a reverse-genetic strategy, enabling a dissection of the K+-uptake apparatus of the root into AKT1 and non-AKT1 components. Membrane potential measurements in root cells demonstrated that the AKT1 component of the wild-type K+ permeability was between 55 and 63% when external [K+] was between 10 and 1,000 microM, and NH4+ was absent. NH4+ specifically inhibited the non-AKT1 component, apparently by competing for K+ binding sites on the transporter(s). This inhibition by NH4+ had significant consequences for akt1 plants: K+ permeability, 86Rb+ fluxes into roots, seed germination, and seedling growth rate of the mutant were each similarly inhibited by NH4+. Wild-type plants were much more resistant to NH4+. Thus, AKT1 channels conduct the K+ influx necessary for the growth of Arabidopsis embryos and seedlings in conditions that block the non-AKT1 mechanism. In contrast to the effects of NH4+, Na+ and H+ significantly stimulated the non-AKT1 portion of the K+ permeability. Stimulation of akt1 growth rate by Na+, a predicted consequence of the previous result, was observed when external [K+] was 10 microM. Collectively, these results indicate that the AKT1 channel is an important component of the K+ uptake apparatus supporting growth, even in the "high-affinity" range of K+ concentrations. In the absence of AKT1 channel activity, an NH4+-sensitive, Na+/H+-stimulated mechanism can suffice.

  2. Sodium hydrogen sulfide inhibits nicotine and lipopolysaccharide-induced osteoclastic differentiation and reversed osteoblastic differentiation in human periodontal ligament cells.

    PubMed

    Lee, Sun-Kyung; Chung, Jong-Hyuk; Choi, Sung-Chul; Auh, Q-Schick; Lee, Young-Man; Lee, Sang-Im; Kim, Eun-Cheol

    2013-05-01

    Although previous studies have demonstrated that hydrogen sulfide (H(2)S) stimulated or inhibited osteoclastic differentiation, little is known about the effects of H(2)S on the differentiation of osteoblasts and osteoclasts. To determine the possible bioactivities of H(2)S on bone metabolism, we investigated the in vitro effects of H(2)S on cytotoxicity, osteoblastic, and osteoclastic differentiation as well as the underlying mechanism in lipopolysaccharide (LPS) and nicotine-stimulated human periodontal ligament cells (hPDLCs). The H(2)S donor, NaHS, protected hPDLCs from nicotine and LPS-induced cytotoxicity and recovered nicotine- and LPS-downregulated osteoblastic differentiation, such as alkaline phosphatase (ALP) activity, mRNA expression of osteoblasts, including ALP, osteopontin (OPN), and osteocalcin (OCN), and mineralized nodule formation. Concomitantly, NaHS inhibited the differentiation of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in mouse bone marrow cells and blocked nicotine- and LPS-induced osteoclastogenesis regulatory molecules, such as RANKL, OPG, M-CSF, MMP-9, TRAP, and cathepsin K mRNA. NaHS blocked nicotine and LPS-induced activation of p38, ERK, MKP-1, PI3K, PKC, and PKC isoenzymes, and NF-κB. The effects of H(2)S on nicotine- and LPS-induced osteoblastic and osteoclastic differentiation were remarkably reversed by MKP-1 enzyme inhibitor (vanadate) and expression inhibitor (triptolide). Taken together, we report for the first time that H(2)S inhibited cytotoxicity and osteoclastic differentiation and recovered osteoblastic differentiation in a nicotine- and periodontopathogen-stimulated hPDLCs model, which has potential therapeutic value for treatment of periodontal and inflammatory bone diseases.

  3. pH-dependent release characteristics of antimony and arsenic from typical antimony-bearing ores.

    PubMed

    Hu, Xingyun; Guo, Xuejun; He, Mengchang; Li, Sisi

    2016-06-01

    The pH-dependent leaching of antimony (Sb) and arsenic (As) from three typical Sb-bearing ores (Banxi, Muli and Tongkeng Antimony Mine) in China was assessed using a pH-static leaching experiment. The pH changes of the leached solutions and pH-dependent leaching of Sb and As occurred in different ways. For the Banxi and Muli Sb ores, alkaline conditions were more favorable for the release of Sb compared to neutral and acidic conditions, but the reverse was true for the pH-dependent release of As. For the Tongkeng Sb ore, unlike the previous two Sb-bearing ores, acidic conditions were more favorable for Sb release than neutral and alkaline conditions. The ores with lower Sb and As contents released higher percentages of their Sb and As after 16day leaching, suggesting that they are the largest potential sources of pollution. This work may provide key information on the geochemistry of Sb and As in the weathering zone. Copyright © 2016. Published by Elsevier B.V.

  4. Growth inhibition of human melanoma tumor cells by the combination of sodium phenylacetate (NaPA) and substituted dextrans and one NaPA-dextran conjugate.

    PubMed

    Gervelas, C; Avramoglou, T; Crépin, M; Jozefonvicz, J

    2002-01-01

    We have studied the cytostatic effects of sodium phenylacetate (NaPA) in association with several substituted dextrans on human tumor melanoma 1205LU cells. We show that NaPA alone inhibits the growth of these cells (IC50 = 3.9 mM) while a weak inhibitory effect appears at a concentration of 37 microM (10 microg/ml) for a dextran methyl carboxylate benzylamide (LS17-DMCB). The precursors of LS17-DMCB [T40 Dextran and carboxymethyl dextran (LS17-DMC)] did not affect the growth of 1205LU cells. To potentiate the inhibitory activity of NaPA at low concentrations (below 5.6 mM), we have tested NaPA and LS17-DMCB in physical mixture (association) or linked together covalently (this conjugate is termed 'LS17-NaPaC'). We have observed an increase of the 1205LU cell growth inhibition effect with NaPA in association (IC50 1.8 mM). For a concentration of 5 mM of NaPA (free in the case of association or linked in the case of conjugate), the association with dextran derivative exhibits a 4.6-fold higher efficacy than with NaPA alone (9 versus 41% surviving fraction), while the conjugate is 1.3-fold smaller (52% growth inhibition). By performing isobologram analysis of the IC50 data, we have shown a synergistic effect for a particular molar ratio of NaPA and LS17-DMCB (NaPA:LS17-DMCB = 0.35).

  5. Sinoporphyrin sodium mediated photodynamic therapy inhibits the migration associated with collapse of F-actin filaments cytoskeleton in MDA-MB-231 cells.

    PubMed

    Wu, Lijie; Wang, Xiaobing; Liu, Quanhong; Wingnang Leung, Albert; Wang, Pan; Xu, Chuanshan

    2016-03-01

    We previously demonstrated that the photosensitizer sinoporphyrin sodium (DVDMS) mediated photodynamic therapy (PDT) had potential advantages in inhibiting tumor growth and metastasis. However, details regarding the mechanism of cell migration inhibition remain unclear. Therefore, in this study, we aimed to investigate the effects of DVDMS-PDT on F-actin filaments, cell migration, apoptotic response and the possible interactions between them in human breast cancer MDA-MB-231 cells. The cell viability was evaluated by MTT and Guava ViaCount assays. The subcellular localization of DVDMS and reactive oxygen species (ROS) generation were analyzed by fluorescence microscope and flow cytometry. FITC-phalloidin was used to evaluate the changes of F-actin filaments. Cell migration was analyzed by scratch assay and Transwell assay. Cell apoptosis was determined by nuclear TUNEL staining and Annexin V-PE/7-AAD assay. Jasplakinolide, an F-actin stabilizer, was applied to dissect the influences of F-actin filaments disruption on cell migration and apoptosis. DVDMS-PDT significantly suppressed cell proliferation, promoted early apoptotic response, triggered collapse of F-actin filaments and inhibited cell migration in MDA-MB-231 cells. Cell migration significantly increased when cells were pretreated with F-actin stabilizer jasplakinolide after PDT, while cell apoptosis was not obviously affected. Moreover, ROS was a key factor in causing collapse of F-actin filaments. We demonstrated that DVDMS-PDT triggered cell apoptosis and collapse of F-actin filaments through the induction of ROS in MDA-MB-231 cells. F-actin filaments contributed to cell migration but produced no obvious effect on cell apoptosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Co-culture with human synovium-derived mesenchymal stem cells inhibits inflammatory activity and increases cell proliferation of sodium nitroprusside-stimulated chondrocytes

    SciTech Connect

    Ryu, Jae-Sung; Jung, Yeon-Hwa; Cho, Mi-Young; Yeo, Jee Eun; Choi, Yun-Jin; Kim, Yong Il; Koh, Yong-Gon

    2014-05-16

    Highlights: • Co-culture of hSDMSCs with SNP-stimulated chondrocytes improves anti-inflammation. • Co-culture system produces IGF-1. • Co-culture system suppresses inflammatory genes expression. • Co-culture system improves cell proliferation. • Exogenous IGF-1 inhibits inflammatory activity in SNP-stimulated chondrocytes. - Abstract: Rheumatoid arthritis (RA) and osteoarthritis (OA) are primarily chronic inflammatory diseases. Mesenchymal stem cells (MSCs) have the ability to differentiate into cells of the mesodermal lineage, and to regulate immunomodulatory activity. Specifically, MSCs have been shown to secrete insulin-like growth factor 1 (IGF-1). The purpose of the present study was to examine the inhibitory effects on inflammatory activity from a co-culture of human synovium-derived mesenchymal stem cells (hSDMSCs) and sodium nitroprusside (SNP)-stimulated chondrocytes. First, chondrocytes were treated with SNP to generate an in vitro model of RA or OA. Next, the co-culture of hSDMSCs with SNP-stimulated chondrocytes reduced inflammatory cytokine secretion, inhibited expression of inflammation activity-related genes, generated IGF-1 secretion, and increased the chondrocyte proliferation rate. To evaluate the effect of IGF-1 on inhibition of inflammation, chondrocytes pre-treated with IGF-1 were treated with SNP, and then the production of inflammatory cytokines was analyzed. Treatment with IGF-1 was shown to significantly reduce inflammatory cytokine secretion in SNP-stimulated chondrocytes. Our results suggest that hSDMSCs offer a new strategy to promote cell-based cartilage regeneration in RA or OA.

  7. Mechanism of inhibition of H+, K(+)-ATPase by sodium 2-[[4-(3- methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl]-1H-benzimidazole (E3810).

    PubMed

    Nochi, S; Yokoyama, Y; Narukawa, M; Ebine, K; Murahashi, M; Kawakami, Y; Asakawa, N; Sato, T

    1996-03-01

    Sodium 2-[[4-(3-methoxypropoxy)-3-methylpyridin-2-yl]methylsulfinyl ]- 1H-benzimidazole (E3810) and omeprazole inhibit gastric acid secretion through inhibition of the activity of H+, K(+)-ATPase present in parietal cell membrane vesicles, by chemical modification of SH groups in the enzyme molecule. In order to clarify the mechanism of the chemical modification, reaction products of E3810 and omeprazole with 2-mercaptoethanol under acidic conditions (pH 3, 4, 5, 6) were isolated by HPLC, and subjected to structural analysis by UV, 1H-NMR and mass spectrometry. E3810 and omeprazole appeared to undergo two kinds of reactions, affording disulfide-type products (type I reaction) and sulfide-type products (type II reaction). The rates of these reactions were determined by HPLC, and the stability of the products in the presence and absence of glutathione was investigated. In the case of E3810, type I reaction was found to proceed faster than type II reaction at every pH value studied. The type I reaction of E3810 was faster than that of omeprazole. The rate of type I reaction decreased at pH 5 and 6, especially for omeprazole, and the contribution of type II reaction increased as the pH of the reaction mixture was increased. The sulfide-type modification products were stable, whereas the formation of the disulfide-type modification products was reversed by the action of endogenous SH compounds such as glutathione. These results suggest that higher inhibitory activity of E3810 against gastric acid secretion and faster recovery of the enzyme activity after inhibition by E3810 can be expected, as compared with those of omeprazole.

  8. In vitro protein synthesis of sugar beet (Beta vulgaris) and maize (Zea mays) is differentially inhibited when potassium is substituted by sodium.

    PubMed

    Faust, Franziska; Schubert, Sven

    2017-09-01

    The substitution of potassium ions (K(+)) by sodium ions (Na(+)) in the nutrition of plants is restricted. It was shown earlier that net protein synthesis is the process which is most sensitive to the substitution of K(+) by Na(+) in young sugar beet. We hypothesized that the activity of ribosomes is inhibited by the substitution. This hypothesis was tested in an in vitro approach. Cytosolic polysomes were isolated from growing leaves of sugar beet and maize by means of differential centrifugation. In vitro systems of both plant species were tested for functionality and comparability. Translation was quantified by the (35)S-methionine incorporation in TCA-precipitable products. The effect of different substitution levels (0%, 20%, 40%, 60%, and 80% substitution of K(+) by Na(+)) on in vitro translation was measured. Translation by polysomes of both plant species was significantly inhibited by the substitution. However, the translation by maize polysomes was more negatively affected by the substitution. A significant decrease in the translation by maize polysomes was observed already when 20% of K(+) were replaced by Na(+), whereas in the case of sugar beet, the translation was inhibited firstly at the substitution level of 40%. The in vitro results show that the process of translation itself is disturbed by the substitution and indicate a higher tolerance of sugar beet polysomes to increased Na(+) concentrations and Na(+)/K(+) ratios compared to polysomes of maize. We propose that this tolerance contributes to the salt resistance of sugar beet. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Molecular basis of the inhibition of the fast inactivation of voltage-gated sodium channel Nav1.5 by tarantula toxin Jingzhaotoxin-II.

    PubMed

    Huang, Ying; Zhou, Xi; Tang, Cheng; Zhang, Yunxiao; Tao, Huai; Chen, Ping; Liu, Zhonghua

    2015-06-01

    Jingzhaotoxin-II (JZTX-II) is a 32-residue peptide from the Chinese tarantula Chilobrachys jingzhao venom, and preferentially inhibits the fast inactivation of the voltage-gated sodium channels (VGSCs) in rat cardiac myocytes. In the present study, we elucidated the action mechanism of JZTX-II inhibiting hNav1.5, a VGSC subtype mainly distributed in human cardiac myocytes. Among the four VGSC subtypes tested, hNav1.5 was the most sensitive to JZTX-II (EC50=125±4nM). Although JZTX-II had little or no effect on steady-state inactivation of the residual currents conducted by hNav1.5, it caused a 10mV hyperpolarized shift of activation. Moreover, JZTX-II increased the recovery rate of hNav1.5 channels, which should lead to a shorter transition from the inactivation to closed state. JZTX-II dissociated from toxin-channel complex via extreme depolarization and subsequently rebound to the channel upon repolarization. Mutagenesis analyses showed that the domain IV (DIV) voltage-sensor domain (VSD) was critical for JZTX-II binding to hNav1.5 and some mutations located in S1-S2 and S3-S4 extracellular loops of hNav1.5 DIV additively reduced the toxin sensitivity of hNav1.5. Our data identified the mechanism underlying JZTX-II inhibiting hNav1.5, similar to scorpion α-toxins, involving binding to neurotoxin receptor site 3.

  10. [Astaxanthin inhibits sodium azide-induced cytotoxicity in hepatocyte L-02 cells probably by H+ transferring function].

    PubMed

    Ma, Jian; Chen, Hai-min; Yan, Xiao-jun; Wang, Feng; Xu, Wei-feng

    2011-05-01

    This study is to investigate the protective effect of astaxanthin against injured hepatocyte L-02 cells induced by sodium azide (NaN3) and reveal the possible mechanisms. Hepatocyte L-02 cells were exposed to 100 mmol.L-1 NaN3 with various concentrations of astaxanthin pre-incubated, then the cell viability was measured by MTT method; The level of reactive oxygen species (ROS) was determined by DCFH-DA method; The changes of mitochondrial membrane potential (MMP) and apoptosis ratio were detected by JC-1 method and Annexin V-FITC/PI double stain method, respectively. Results showed that after cells were exposed to 100 mmol.L-1 NaN3 for 3 hours, the cell viability significantly decreased; ROS level and the percentage of late phase apoptosis increased obviously; MMP was also declined. When cells were pretreated with astaxanthin, the cell damage and late phase apoptosis ratio reduced and MMP was maintained. However, the level of ROS showed insignificant decrease (P>0.05). The beneficial concentration of astaxanthin in improving cell viability and MMP was not in a dose dependent manner and the most effective of which was 0.10 nmol.L-1 (P<0.01). In order to reveal its possible non-antioxidant mechanism, mitochondrial membrane was imitated and H+ transferring function of astaxanthin was also detected by bilayer lipid membrane (BLM) method. Results showed that 2.0% astaxanthin could transfer H+ efficiently. These suggested the mechanisms of astaxanthin in protection of hepatocyte L-02 cells not via its ROS quenching capability but via its H+ transferring function, which improved the mitochondrial function and had the sequence biology effects.

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

    PubMed Central

    Yeom, Yiseul; Kim, Yuri

    2015-01-01

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

  12. Sodium Chloride Inhibits the Growth and Infective Capacity of the Amphibian Chytrid Fungus and Increases Host Survival Rates

    PubMed Central

    Stockwell, Michelle Pirrie; Clulow, John; Mahony, Michael Joseph

    2012-01-01

    The amphibian chytrid fungus Batrachochytrium dendrobatidis is a recently emerged pathogen that causes the infectious disease chytridiomycosis and has been implicated as a contributing factor in the global amphibian decline. Since its discovery, research has been focused on developing various methods of mitigating the impact of chytridiomycosis on amphibian hosts but little attention has been given to the role of antifungal agents that could be added to the host's environment. Sodium chloride is a known antifungal agent used routinely in the aquaculture industry and this study investigates its potential for use as a disease management tool in amphibian conservation. The effect of 0–5 ppt NaCl on the growth, motility and survival of the chytrid fungus when grown in culture media and its effect on the growth, infection load and survivorship of infected Peron's tree frogs (Litoria peronii) in captivity, was investigated. The results reveal that these concentrations do not negatively affect the survival of the host or the pathogen. However, concentrations greater than 3 ppt significantly reduced the growth and motility of the chytrid fungus compared to 0 ppt. Concentrations of 1–4 ppt NaCl were also associated with significantly lower host infection loads while infected hosts exposed to 3 and 4 ppt NaCl were found to have significantly higher survival rates. These results support the potential for NaCl to be used as an environmentally distributed antifungal agent for the prevention of chytridiomycosis in susceptible amphibian hosts. However, further research is required to identify any negative effects of salt exposure on both target and non-target organisms prior to implementation. PMID:22590639

  13. Structural Basis for the Inhibition of Voltage-gated Sodium Channels by Conotoxin μO§-GVIIJ.

    PubMed

    Green, Brad R; Gajewiak, Joanna; Chhabra, Sandeep; Skalicky, Jack J; Zhang, Min-Min; Rivier, Jean E; Bulaj, Grzegorz; Olivera, Baldomero M; Yoshikami, Doju; Norton, Raymond S

    2016-03-25

    Cone snail toxins are well known blockers of voltage-gated sodium channels, a property that is of broad interest in biology and therapeutically in treating neuropathic pain and neurological disorders. Although most conotoxin channel blockers function by direct binding to a channel and disrupting its normal ion movement, conotoxin μO§-GVIIJ channel blocking is unique, using both favorable binding interactions with the channel and a direct tether via an intermolecular disulfide bond. Disulfide exchange is possible because conotoxin μO§-GVIIJ contains anS-cysteinylated Cys-24 residue that is capable of exchanging with a free cysteine thiol on the channel surface. Here, we present the solution structure of an analog of μO§-GVIIJ (GVIIJ[C24S]) and the results of structure-activity studies with synthetic μO§-GVIIJ variants. GVIIJ[C24S] adopts an inhibitor cystine knot structure, with two antiparallel β-strands stabilized by three disulfide bridges. The loop region linking the β-strands (loop 4) presents residue 24 in a configuration where it could bind to the proposed free cysteine of the channel (Cys-910, rat NaV1.2 numbering; at site 8). The structure-activity study shows that three residues (Lys-12, Arg-14, and Tyr-16) located in loop 2 and spatially close to residue 24 were also important for functional activity. We propose that the interaction of μO§-GVIIJ with the channel depends on not only disulfide tethering via Cys-24 to a free cysteine at site 8 on the channel but also the participation of key residues of μO§-GVIIJ on a distinct surface of the peptide. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Inhibition by sodium cromoglycate of bronchoconstriction stimulated by respiratory heat loss: comparison of pressurised aerosol and powder.

    PubMed Central

    Latimer, K M; Roberts, R; Morris, M M; Hargreave, F E

    1984-01-01

    The protective effect was examined of three doses (2, 10, and 20 mg) of sodium cromoglycate inhaled from a pressurised metered dose inhaler on the response to isocapnic hyperventilation of cold dry air in 10 asthmatic subjects. This was compared with the effect of cromoglycate powder (20 mg) inhaled from a Spincap and with placebo given on two occasions. The medications were inhaled on separate days, in random order and with the use of a double blind double dummy technique, 20 minutes before isocapnic hyperventilation of two fold increasing volumes of air (-15 degrees C, 0% humidity) to produce a 20% fall in the post-treatment FEV1. The response was expressed as the provocative dose of respiratory heat loss required to cause a fall in FEV1 of 15% (PD15, kcal/min). The mean baseline spirometric indices exceeded 85% of predicted normal values on each test day; both placebo treatments reduced the baseline FEV1 by comparison with all active treatments (p less than 0.0001). Comparison of the PD15 on the two placebo days confirmed excellent reproducibility. All doses of cromoglycate shifted the respiratory heat loss dose-response curve to the right of the placebo curve; PD15 after all active treatments exceeded PD15 after placebo (p less than 0.0001). There was no cromoglycate dose-response relationship between the three doses of aerosol (p greater than 0.05), or between any dose of aerosol and powder (p greater than 0.05). It is concluded that cromoglycate aerosol inhaled from a pressurised inhaler in a dose of 2 mg gives the same magnitude of protection against bronchoconstriction stimulated by airway cooling as 20 mg of pressurised aerosol or powder from a Spincap. PMID:6426073

  15. Acidified sodium chlorite treatment for inhibition of Listeria monocytogenes growth on the surface of cooked roast beef.

    PubMed

    Beverly, Richelle L; Janes, Marlene E; Oliver, Grady

    2006-02-01

    The effects of acidified sodium chlorite (ASC) against Listeria monocytogenes on the surface of cooked roast beef were investigated. L. monocytogenes, strain V7, serotype 1/2a, was inoculated at numbers of 6.0 log CFU/g onto 5-g cubes of cooked regular or spicy roast beef. The samples were allowed to air dry for 1 h. The cooked roast beef samples were dipped into ASC or sprayed with ASC solutions of 250, 500, 750, or 1,000 ppm, then placed in bags with or without a vacuum and refrigerated at 4 degrees C. L. monocytogenes counts were determined after 0, 7, 14, 21, and 28 days of storage by spread plating roast beef samples onto Oxford agar plates that were incubated at 37 degrees C for 48 h. At day 28, the number of L. monocytogenes on the > or = 500 ppm ASC-treated spicy roast beef samples had count reductions that were >4.0 log CFU/g, whereas the same concentrations of ASC-treated regular roast beef samples had approximately a 2.5 log CFU/g reduction in L. monocytogenes counts when compared with the untreated samples. No significant differences (P > 0.05) were observed in L. monocytogenes counts between the vacuum- or nonvacuum-packaged ASC-treated cooked roast beef samples. Sensory evaluation showed no significant differences (P > 0.05) between ASC-treated and untreated roast beef. ASC can be used as a processing aid in the form of a dip or spray treatment to control L. monocytogenes on the surface of cooked roast beef.

  16. Sodium meta-arsenite ameliorates hyperglycemia in obese diabetic db/db mice by inhibition of hepatic gluconeogenesis.

    PubMed

    Lee, Young-Sun; Lee, Eun-Kyu; Oh, Hyun-Hee; Choi, Cheol Soo; Kim, Sujong; Jun, Hee-Sook

    2014-01-01

    Sodium meta-arsenite (SA) is implicated in the regulation of hepatic gluconeogenesis-related genes in vitro; however, the effects in vivo have not been studied. We investigated whether SA has antidiabetic effects in a type 2 diabetic mouse model. Diabetic db/db mice were orally intubated with SA (10 mg kg(-1) body weight/day) for 8 weeks. We examined hemoglobin A1c (HbA1c), blood glucose levels, food intake, and body weight. We performed glucose, insulin, and pyruvate tolerance tests and analyzed glucose production and the expression of gluconeogenesis-related genes in hepatocytes. We analyzed energy metabolism using a comprehensive animal metabolic monitoring system. SA-treated diabetic db/db mice had reduced concentrations of HbA1c and blood glucose levels. Exogenous glucose was quickly cleared in glucose tolerance tests. The mRNA expressions of genes for gluconeogenesis-related enzymes, glucose 6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK) were significantly reduced in the liver of SA-treated diabetic db/db mice. In primary hepatocytes, SA treatment decreased glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear factor 4 alpha (HNF-4α) mRNA. Small heterodimer partner (SHP) mRNA expression was increased in hepatocytes dependent upon the SA concentration. The expression of Sirt1 mRNA and protein was reduced, and acetylated forkhead box protein O1 (FoxO1) was induced by SA treatment in hepatocytes. In addition, SA-treated diabetic db/db mice showed reduced energy expenditure. Oral intubation of SA ameliorates hyperglycemia in db/db mice by reducing hepatic gluconeogenesis through the decrease of Sirt1 expression and increase in acetylated FoxO1.

  17. Structural Basis for the Inhibition of Voltage-gated Sodium Channels by Conotoxin μO§-GVIIJ*

    PubMed Central

    Green, Brad R.; Gajewiak, Joanna; Chhabra, Sandeep; Skalicky, Jack J.; Zhang, Min-Min; Rivier, Jean E.; Bulaj, Grzegorz; Yoshikami, Doju

    2016-01-01

    Cone snail toxins are well known blockers of voltage-gated sodium channels, a property that is of broad interest in biology and therapeutically in treating neuropathic pain and neurological disorders. Although most conotoxin channel blockers function by direct binding to a channel and disrupting its normal ion movement, conotoxin μO§-GVIIJ channel blocking is unique, using both favorable binding interactions with the channel and a direct tether via an intermolecular disulfide bond. Disulfide exchange is possible because conotoxin μO§-GVIIJ contains an S-cysteinylated Cys-24 residue that is capable of exchanging with a free cysteine thiol on the channel surface. Here, we present the solution structure of an analog of μO§-GVIIJ (GVIIJ[C24S]) and the results of structure-activity studies with synthetic μO§-GVIIJ variants. GVIIJ[C24S] adopts an inhibitor cystine knot structure, with two antiparallel β-strands stabilized by three disulfide bridges. The loop region linking the β-strands (loop 4) presents residue 24 in a configuration where it could bind to the proposed free cysteine of the channel (Cys-910, rat NaV1.2 numbering; at site 8). The structure-activity study shows that three residues (Lys-12, Arg-14, and Tyr-16) located in loop 2 and spatially close to residue 24 were also important for functional activity. We propose that the interaction of μO§-GVIIJ with the channel depends on not only disulfide tethering via Cys-24 to a free cysteine at site 8 on the channel but also the participation of key residues of μO§-GVIIJ on a distinct surface of the peptide. PMID:26817840

  18. Flow analysis-hydride generation-gas phase derivative molecular absorption spectrophotometric determination of antimony in oral homeopathic products ("AntimoniumTartaricum") formulated under alcoholic medium.

    PubMed

    Gallignani, Máximo; Ovalles, Fernando; Brunetto, Maria Del Rosario; Burguera, Marcela; Burguera, Jose Luis

    2005-12-15

    In this work, a flow analysis-hydride generation-gas phase derivative molecular absorption-(UV) spectrophotometric method has been developed for the direct determination of antimony in aqueous and hydro-alcoholic samples. Antimony (III) from undiluted samples is directly transformed into the gaseous stibine (SbH(3)) form by on-line reaction with sodium tetrahydroborate (NaBH(4)) in acidic medium (HCl). The gaseous phase generated is separated from the liquid phase using a commercial gas-liquid separator, and swept - with the help of a carrier gas (N(2)) stream - into a quartz gas cell (10cm pathlength); where the corresponding absorption spectrum is acquired in a continuous mode over the 190-300nm wavelength range, using a conventional spectrophotometer. A derivative strategy was selected in order to avoid the strong spectral interference of the ethanol vapor on the gaseous SbH(3) absorption spectrum. In this way, the peak height at 223nm of the second order derivative spectrum appears as a clear, clean and interference free analytical signal, which allows the direct determination of antimony. The recovery values obtained from homeopathic formulations (prepared in alcoholic medium) spiked with know amounts of antimony ranged between 97.5 and 103%. The method provides a dynamic range from 0.20 to 30mgSbl(-1). The precision (RDS), evaluated by replicate analysis (n=5) of samples and standard solution containing between 2.5 and 15mgSbl(-1) was in all cases lower than 1.2%. The proposed method was applied to the determination of antimony in commercial homeopathic products ("Antimonium Tartaricum") prepared in hydro-alcoholic medium; and showed to be simple, precise, and accurate.

  19. Possible Links between Sickle Cell Crisis and Pentavalent Antimony

    PubMed Central

    Garcerant, Daniel; Rubiano, Luisa; Blanco, Victor; Martinez, Javier; Baker, Nancy C.; Craft, Noah

    2012-01-01

    For over 60 years, pentavalent antimony (Sbv) has been the first-line treatment of leishmaniasis. Sickle cell anemia is a disease caused by a defect in red blood cells, which among other things can cause vasooclusive crisis. We report the case of a 6-year-old child with leishmaniasis who during treatment with meglumine antimoniate developed a sickle cell crisis (SCC). No previous reports describing the relationship between antimonial drugs and sickle cell disease were found. Reviews of both the pathophysiology of SCC and the mechanism of action of Sbv revealed that a common pathway (glutathione) may have resulted in the SCC. ChemoText, a novel database created to predict chemical-protein-disease interactions, was used to perform a more expansive and systematic review that was able to support the association between glutathione, Sbv, and SCC. Although suggestive evidence to support the hypothesis, additional research at the bench would be needed to prove Sbv caused the SCC. PMID:22665619

  20. Role of the ABC Transporter MRPA (PGPA) in Antimony Resistance in Leishmania infantum Axenic and Intracellular Amastigotes

    PubMed Central

    El Fadili, Karima; Messier, Nadine; Leprohon, Philippe; Roy, Gaétan; Guimond, Chantal; Trudel, Nathalie; Saravia, Nancy G.; Papadopoulou, Barbara; Légaré, Danielle; Ouellette, Marc

    2005-01-01

    Antimonial compounds are the mainstay for the treatment of infections with the protozoan parasite Leishmania. We present our studies on Leishmania infantum amastigote parasites selected for resistance to potassium antimonyl tartrate [Sb(III)]. Inside macrophages, the Sb(III)-selected cells are cross-resistant to sodium stibogluconate (Pentostam), the main drug used against Leishmania. Putative alterations in the level of expression of more than 40 genes were compared between susceptible and resistant axenic amastigotes using customized DNA microarrays. The expression of three genes coding for the ABC transporter MRPA (PGPA), S-adenosylhomocysteine hydrolase, and folylpolyglutamate synthase was found to be consistently increased. The levels of cysteine were found to be increased in the mutant. Transfection of the MRPA gene was shown to confer sodium stibogluconate resistance in intracellular parasites. This MRPA-mediated resistance could be reverted by using the glutathione biosynthesis-specific inhibitor buthionine sulfoximine. These results highlight for the first time the role of MRPA in antimony resistance in the amastigote stage of the parasite and suggest a strategy for reversing resistance. PMID:15855523

  1. Development of Secondary Antimony Oxides from Metallurgical Slags for the Application in Plastic Products

    NASA Astrophysics Data System (ADS)

    Binz, Florian; Friedrich, Bernd

    Bottom-up process design is performed for an antimony white fuming approach from antimonyrich lead refining residues. Thermochemical modelling is used to evaluate process boundaries regarding temperature and slag composition allowing the fuming of qualified antimony white from mentioned residues. Fuming boundaries indicate that state of the art drosses are not suitable for fuming qualified antimony white. Slag conditioning by antimony enrichment of the slag has to be carried out in advance. Carbothermic reduction of lead oxide from named oxides is simulated and evaluated in lab scale to achieve optimal slag enrichment while avoiding antimony losses to the metal phase.

  2. Antimony recycling in the United States in 2000

    USGS Publications Warehouse

    Carlin Jr., James F.

    2006-01-01

    The importance of recycling has become more obvious as concerns about the environment and import dependence have grown in recent years. When materials are recycled, fewer natural resources are consumed, and less waste products go to landfills or pollute the water and air. This study, one of a series of reports on metals recycling in 2000, discusses the flow of antimony from mining through its uses and disposal with emphasis on recycling. In 2000, the recycling efficiency for antimony was estimated to be 89 percent, and the recycling rate was about 20 percent.

  3. Standardization of intralesional meglumine antimoniate treatment for cutaneous leishmaniasis.

    PubMed

    Duque, Maria Cristina de Oliveira; Vasconcellos, Érica de Camargo Ferreira E; Pimentel, Maria Inês Fernandes; Lyra, Marcelo Rosandiski; Pacheco, Sandro Javier Bedoya; Marzochi, Mauro Celio de Almeida; Rosalino, Cláudia Maria Valete; Schubach, Armando de Oliveira

    2016-01-01

    Intralesional treatment for cutaneous leishmaniasis has been applied for over 30 years at the Oswaldo Cruz Foundation, Rio de Janeiro, with good therapeutic results and without relevant systemic toxicity. Meglumine antimoniate was injected subcutaneously, using a long medium-caliber needle (for example, 30mm × 0.8mm); patients received 1-3 injections, with 15-day intervals. The technique is described in detail sufficient to enable replication. The treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate is a simple, effective, and safe technique, which may be used in basic healthcare settings.

  4. Antimony Based III-V Thermophotovoltaic Devices

    SciTech Connect

    CA Wang

    2004-06-09

    Antimony-based III-V thermophotovoltaic (TPV) cells are attractive converters for systems with low radiator temperature around 1100 to 1700 K, since these cells potentially can be spectrally matched to the thermal source. Cells under development include GaSb and the lattice-matched GaInAsSb/GaSb and InPAsSb/InAs quaternary systems. GaSb cell technology is the most mature, owing in part to the relative ease in preparation of the binary alloy compared to quaternary GaInAsSb and InPAsSb alloys. Device performance of 0.7-eV GaSb cells exceeds 90% of the practical limit. GaInAsSb TPV cells have been the primary focus of recent research, and cells with energy gap E{sub g} ranging from {approx}0.6 to 0.49 eV have been demonstrated. Quantum efficiency and fill factor approach theoretical limits. Open-circuit voltage factor is as high as 87% of the practical limit for the higher-E{sub g} cells, but degrades to below 80% with decreasing E{sub g} of the alloy, which might be due to Auger recombination. InPAsSb cells are the least studied, and a cell with E{sub g} = 0.45-eV has extended spectral response out to 4.3 {micro}m. This paper briefly reviews the main contributions that have been made for antimonide-based TPV cells, and suggests additional studies for further performance enhancements.

  5. An improved method for the determination of trace levels of arsenic and antimony in geological materials by automated hydride generation-atomic absorption spectroscopy

    USGS Publications Warehouse

    Crock, J.G.; Lichte, F.E.

    1982-01-01

    An improved, automated method for the determination of arsenic and antimony in geological materials is described. After digestion of the material in sulfuric, nitric, hydrofluoric and perchloric acids, a hydrochloric acid solution of the sample is automatically mixed with reducing agents, acidified with additional hydrochloric acid, and treated with a sodium tetrahydroborate solution to form arsine and stibine. The hydrides are decomposed in a heated quartz tube in the optical path of an atomic absorption spectrometer. The absorbance peak height for arsenic or antimony is measured. Interferences that exist are minimized to the point where most geological materials including coals, soils, coal ashes, rocks and sediments can be analyzed directly without use of standard additions. The relative standard deviation of the digestion and the instrumental procedure is less than 2% at the 50 ??g l-1 As or Sb level. The reagent-blank detection limit is 0.2 ??g l-1 As or Sb. ?? 1982.

  6. Oral Delivery of Meglumine Antimoniate-β-Cyclodextrin Complex for Treatment of Leishmaniasis

    PubMed Central

    Demicheli, Cynthia; Ochoa, Rosemary; da Silva, José B. B.; Falcão, Camila A. B.; Rossi-Bergmann, Bartira; de Melo, Alan L.; Sinisterra, Ruben D.; Frézard, Frédéric

    2004-01-01

    The need for daily parenteral administration represents one of the most serious limitations in the clinical use of pentavalent antimonials against leishmaniasis. In this work, we investigated the ability of β-cyclodextrin to enhance the oral absorption of antimony and to promote the oral efficacy of meglumine antimoniate against experimental cutaneous leishmaniasis. The occurrence of interactions between β-cyclodextrin and meglumine antimoniate was demonstrated through the changes induced in the spin lattice relaxation times of protons in both compounds. When free and complexed meglumine antimoniate were given orally to Swiss mice, plasma antimony levels were found to be about three times higher for the meglumine antimoniate-β-cyclodextrin complex than for the free drug. Antileishmanial efficacy was evaluated in BALB/c mice experimentally infected with Leishmania amazonensis. Animals treated daily with the complex (32 mg of Sb/kg of body weight) by the oral route developed significantly smaller lesions than those treated with meglumine antimoniate (120 mg of Sb/kg) and control animals (treated with saline). The effectiveness of the complex given orally was equivalent to that of meglumine antimoniate given intraperitoneally at a twofold-higher antimony dose. The antileishmanial efficacy of the complex was confirmed by the significantly lower parasite load in the lesions of treated animals than in saline-treated controls. This work reports for the first time the effectiveness of an oral formulation for pentavalent antimonials. PMID:14693525

  7. Sodium orthovanadate associated with pharmacological doses of ascorbate causes an increased generation of ROS in tumor cells that inhibits proliferation and triggers apoptosis

    SciTech Connect

    Günther, T-hat nia Mara Fischer; Kviecinski, Maicon Roberto; Baron, Carla Cristine; Felipe, Karina Bettega; Farias, Mirelle Sifroni; Ourique da Silva, Fabiana; Bücker, Nádia Cristina Falcão; Pich, Claus Tröger; Ferreira, Eduardo Antonio; Filho, Danilo Wilhelm; Verrax, Julien; Calderon, Pedro Buc; Pedrosa, Rozangela Curi

    2013-01-18

    Graphical abstract: -- Abstract: Pharmacological doses of ascorbate were evaluated for its ability to potentiate the toxicity of sodium orthovanadate (Na{sub 3}VO{sub 4}) in tumor cells. Cytotoxicity, inhibition of cell proliferation, generation of ROS and DNA fragmentation were assessed in T24 cells. Na{sub 3}VO{sub 4} was cytotoxic against T24 cells (EC{sub 50} = 5.8 μM at 24 h), but in the presence of ascorbate (100 μM) the EC{sub 50} fell to 3.3 μM. Na{sub 3}VO{sub 4} plus ascorbate caused a strong inhibition of cell proliferation (up to 20%) and increased the generation of ROS (4-fold). Na{sub 3}VO{sub 4} did not directly cleave plasmid DNA, at this aspect no synergism was found occurring between Na{sub 3}VO{sub 4} and ascorbate once the resulting action of the combination was no greater than that of both substances administered separately. Cells from Ehrlich ascites carcinoma-bearing mice were used to determine the activity of antioxidant enzymes, the extent of the oxidative damage and the type of cell death. Na{sub 3}VO{sub 4} alone, or combined with ascorbate, increased catalase activity, but only Na{sub 3}VO{sub 4} plus ascorbate increased superoxide dismutase activity (up to 4-fold). Oxidative damage on proteins and lipids was higher due to the treatment done with Na{sub 3}VO{sub 4} plus ascorbate (2–3-fold). Ascorbate potentiated apoptosis in tumor cells from mice treated with Na{sub 3}VO{sub 4}. The results indicate that pharmacological doses of ascorbate enhance the generation of ROS induced by Na{sub 3}VO{sub 4} in tumor cells causing inhibition of proliferation and apoptosis. Apoptosis induced by orthovanadate and ascorbate is closer related to inhibition on Bcl-xL and activation of Bax. Our data apparently rule out a mechanism of cell demise p53-dependent or related to Cdk2 impairment.

  8. Ziram and sodium N,N-dimethyldithiocarbamate inhibit ubiquitin activation through intracellular metal transport and increased oxidative stress in HEK293 cells.

    PubMed

    Dennis, Kathleen E; Valentine, William M

    2015-04-20

    Ubiquitin activating enzyme E1 plays a pivotal role in ubiquitin based protein signaling through regulating the initiating step of the cascade. Previous studies demonstrated that E1 is inhibited by covalent modification of reactive cysteines contained within the ubiquitin-binding groove and by conditions that increase oxidative stress and deplete cellular antioxidants. In this study, we determined the relative contribution of covalent adduction and oxidative stress to E1 inhibition produced by ziram and sodium N,N-dimethyldithiocarbamate (DMDC) in HEK293 cells. Although no dithiocarbamate-derived E1 adducts were identified on E1 using shotgun LC/MS/MS for either ziram or DMDC, both dithiocarbamates significantly decreased E1 activity, with ziram demonstrating greater potency. Ziram increased intracellular levels of zinc and copper, DMDC increased intracellular levels of only copper, and both dithiocarbamates enhanced oxidative injury evidenced by elevated levels of protein carbonyls and expression of heme oxygenase-1. To assess the contribution of intracellular copper transport to E1 inhibition, coincubations were performed with the copper chelator triethylenetetramine hydrochloride (TET). TET significantly protected E1 activity for both of the dithiocarbamates and decreased the associated oxidative injury in HEK293 cells as well as prevented dithiocarbamate-mediated lipid peroxidation assayed using an ethyl aracidonate micelle system. Because TET did not completely ameliorate intracellular transport of copper or zinc for ziram, TET apparently maintained E1 activity through its ability to diminish dithiocarbamate-mediated oxidative stress. Experiments to determine the relative contribution of elevated intracellular zinc and copper were performed using a metal free incubation system and showed that increases in either metal were sufficient to inhibit E1. To evaluate the utility of the HEK293 in vitro system for screening environmental agents, a series of additional

  9. Abciximab does not inhibit the increase of thrombin generation produced in platelet-rich plasma in vitro by sodium arachidonate or tissue factor.

    PubMed

    Altman, Raul; Scazziota, Alejandra; Santoro, Silvina; Gonzalez, Claudio

    2005-07-01

    Aspirin and platelet membrane glycoprotein (GP) IIb/IIIa blockers are currently used for acute coronary events, and in percutaneous coronary intervention for preventing further coronary outcomes, because they inhibit platelet function. Aspirin also inhibits thrombin generation (TG) in platelet-rich plasma (PRP) activated by sodium arachidonate (AA). The effect of the platelet membrane GP IIb-IIIa (integrin alpha(IIb)beta(3)) blocker abciximab on thrombin generation was studied in vitro using PRP. Thirty healthy volunteers taking no medication, and 28 volunteers who had taken aspirin (160 mg/day for 3-4 days), were included in the protocol. Control or in vivo aspirinated PRP, stimulated or not by AA or tissue factor (TF), was investigated for the inhibitory effect of abciximab pre-incubated for 3 minutes. AA and TF added in vitro activated non-aspirinated PRP: lag-time (LT) and time to peak (TTP) were significantly shortened. Peak TG (PTG) and endogenous thrombin potential (ETG) were increased by AA but not TF; thus, AA seems to be more efficient than TF for TG in this system. Abciximab added in vitro to non-activated, non-aspirinated PRP had no effect on LT, TTP, or ETP, but caused a decrease in PTG that was not statistically significant. Abciximab (3 or 4 microg/mL) added in vitro to AA or TF-activated, non-aspirinated PRP produced no effect on TG, although in aspirinated platelets both LT and time to peak were prolonged. AA as well as TF added in vitro to PRP or in vivo aspirinated PRP increased TG, although AA seems to be more efficient in our assay system. Abciximab, which affects non-aspirinated, nonactivated PRP weakly, has no effect on AA or TF in activated control PRP or in vivo aspirinated PRP.

  10. Enhanced expression of epithelial sodium channels causes salt-induced hypertension in mice through inhibition of the α2-isoform of Na+, K+-ATPase.

    PubMed

    Leenen, Frans H H; Hou, Xiaohong; Wang, Hong-Wei; Ahmad, Monir

    2015-05-01

    Knockout of the Nedd4-2 gene in mice results in overexpression of epithelial sodium channels (ENaC) on the plasma membrane in the kidney, choroid plexus and brain nuclei. These mice exhibit enhanced pressor responses to CSF [Na(+)] as well as dietary salt-induced hypertension which both can be blocked by central infusion of the ENaC blocker benzamil. Functional studies suggest that ENaC activation in the CNS results in release of endogenous ouabain (EO) and inhibition of the α2-isoform of Na(+), K(+)-ATPase. To test this concept more specifically, we studied Nedd4-2(-/-) mice expressing the ouabain-resistant α2R/R-isoform of Na(+), K(+)-ATPase. Intracerebroventricular (icv) infusion of Na(+)-rich aCSF (225 mmol/L Na(+) at 0.4 μL/min) increased MAP by 10-15 mmHg in wild-type mice and by 25-30 mmHg in Nedd4-2(-/-) mice, but by only ~5 mmHg in α2R/R and in α2R/R/Nedd4-2(-/-) mice. Icv infusion of EO-binding Fab fragments also blocked the BP response in Nedd4-2(-/-) mice. In Nedd4-2(-/-) mice, 8% high-salt diet increased MAP by 25-30 mmHg, but in α2R/R/Nedd4-2(-/-) mice, it increased by only 5-10 mmHg. In contrast, Nedd4-2(-/-) or α2R/R did not affect the hypertension caused by sc infusion of Ang II. These findings substantiate the concept that enhanced ENaC activity causes salt-induced pressor responses mainly through EO inhibiting the α2-isoform of Na(+), K(+)-ATPase in the brain.

  11. A new approach to glucose control in type 2 diabetes: the role of kidney sodium-glucose co-transporter 2 inhibition.

    PubMed

    Basile, Jan

    2011-07-01

    Hyperglycemia is a defining characteristic of type 2 diabetes mellitus and is a major risk factor associated with the development of many microvascular complications. There are numerous therapies currently available to treat hyperglycemia, but glycemic control rates remain poor. One potential reason is the decline in ß-cell function over time, which decreases the effectiveness of therapies that rely on insulin action. The kidney occupies a central position in the control of glucose homeostasis by its role in gluconeogenesis and by regulating glucose excretion. Under normal conditions, glucose filtered by the kidney is virtually totally reabsorbed in the proximal tubule by the sodium-glucose co-transporter 2 (SGLT2). Inhibition of SGLT2 is an attractive, insulin-independent target for increasing glucose excretion in the setting of hyperglycemia. A number of SGLT2 inhibitors have been synthesized, and results from preclinical studies have shown that they increase glucose excretion and normalize plasma glucose in diabetic models. Initial clinical data are promising and suggest that SGLT2 inhibitors may be a new therapeutic option for treating type 2 diabetes mellitus.

  12. Sodium Benzoate, a Food Additive and a Metabolite of Cinnamon, Modifies T Cells at Multiple Steps and Inhibits Adoptive Transfer of Experimental Allergic Encephalomyelitis1

    PubMed Central

    Brahmachari, Saurav; Pahan, Kalipada

    2007-01-01

    Experimental allergic encephalomyelitis (EAE) is the animal model for multiple sclerosis. This study explores a novel use of sodium benzoate (NaB), a commonly used food additive and a Food and Drug Administration-approved nontoxic drug for urea cycle disorders, in treating the disease process of relapsing-remitting EAE in female SJL/J mice. NaB, administered through drinking water at physiologically tolerable doses, ameliorated clinical symptoms and disease progression of EAE in recipient mice and suppressed the generation of encephalitogenic T cells in donor mice. Histological studies reveal that NaB effectively inhibited infiltration of mononuclear cells and demyelination in the spinal cord of EAE mice. Consequently, NaB also suppressed the expression of proinflammatory molecules and normalized myelin gene expression in the CNS of EAE mice. Furthermore, we observed that NaB switched the differentiation of myelin basic protein-primed T cells from Th1 to Th2 mode, enriched regulatory T cell population, and down-regulated the expression of various contact molecules in T cells. Taken together, our results suggest that NaB modifies encephalitogenic T cells at multiple steps and that NaB may have therapeutic importance in multiple sclerosis. PMID:17579047

  13. Antagonistic role of tea against sodium arsenite-induced oxidative DNA damage and inhibition of DNA repair in Swiss albino mice.

    PubMed

    Sinha, Dona; Roy, Madhumita

    2011-01-01

    Arsenic (As) contamination in groundwater is of increasing health concern in West Bengal, India. Arsenic has been associated with various human cancers, but the precise mechanism of its co-carcinogenic action is not clearly elucidated. Oxidative stress and defective repair mechanisms may promote accumulation of mutations and may be a stepping stone for carcinogenesis. Prevention of arsenic-induced oxidative stress and repair inhibition may reduce the chances of initiation of cancer. Tea polyphenols are reported to have excellent chemopreventive properties against cancer. This study aimed to elucidate the role of tea against arsenic-induced formation of 8-hydroxy-2'-deoxyguanosine (8OHdG) and arsenic-suppressed DNA repair in Swiss albino mice. Both green and black tea gave fruitful results in the reduction of 8OHdG and 8-oxoguanine DNA glycosylase (OGG1) in Swiss albino mice administered sodium arsenite (As III). DNA repair enzymes--such as PARP1, DNA β-polymerase, XRCC1, DNA ligase III, DNA protein kinase (catalytic subunit), XRCC 4, DNA ligase IV, and DNA topoisomerase IIβ--were induced by the phytochemicals at both the protein and genetic levels. Thus, tea polyphenols may prove effective in treating arsenic-induced carcinogenesis.

  14. Sodium cromoglycate inhibits absorption of the major soybean allergen, Gly m Bd 30K, in mice and human intestinal Caco-2 cells.

    PubMed

    Weangsripanaval, Thanakorn; Murota, Kaeko; Murakami, Yoko; Kominami, Masaru; Kusudo, Tatsuya; Moriyama, Tatsuya; Ogawa, Tadashi; Kawada, Teruo

    2006-11-01

    Our previous data showed that Gly m Bd 30K was absorbed from the gastrointestinal tract and circulated in blood in mice. This study was conducted to determine the mechanism and identify the inhibitor of such absorption. Using sandwich ELISA and immunoblotting, we found that intact Gly m Bd 30K was absorbed from apical to basolateral solutions and intracellularly accumulated by Caco-2 cells in a dose- and time-dependent manner. The absorption and intracellular accumulation of Gly m Bd 30K were significantly suppressed when Caco-2 cells were treated with sodium cromoglycate (SCG) (0-50 mmol/L) in a dose-dependent manner. In 24-d-old mice orally treated with SCG (10-1000 mg/kg body weight), plasma Gly m Bd 30K concentration decreased significantly 30-120 min after Gly m Bd 30K (2000 mg/kg body weight) administration. Moreover, inhibitors that suppress the clathrin-dependent endocytosis dansylcadaverine, the caveolae-dependent endocytosis nystatin and clathrin, and the caveolae-dependent endocytosis methyl-beta-cyclodextrin had inhibitory effects on the absorption and intracellular accumulation of Gly m Bd 30K by Caco-2 cells. These data indicate that Gly m Bd 30K is absorbed and intracellularly accumulated in Caco-2 cells via clathrin- or caveolae-dependent endocytosis. We propose that the absorption and intracellular accumulation of Gly m Bd 30K are inhibited by SCG via clathrin- or caveolae-dependent endocytosis.

  15. Inhibition of the sodium-translocating NADH-ubiquinone oxidoreductase [Na+-NQR] decreases cholera toxin production in Vibrio cholerae O1 at the late exponential growth phase

    PubMed Central

    Minato, Yusuke; Fassio, Sara R.; Reddekopp, Rylan L.; Häse, Claudia C.

    2014-01-01

    Two virulence factors produced by Vibrio cholerae, cholera toxin (CT) and toxin-corregulated pilus (TCP), are indispensable for cholera infection. ToxT is the central regulatory protein involved in activation of CT and TCP expression. We previously reported that lack of a respiration-linked sodium-translocating NADH–ubiquinone oxidoreductase (Na+-NQR) significantly increases toxT transcription. In this study, we further characterized this link and found that Na+-NQR affects toxT expression only at the early-log growth phase, whereas lack of Na+-NQR decreases CT production after the mid-log growth phase. Such decreased CT production was independent of toxT and ctxB transcription. Supplementing a respiratory substrate, L-lactate, into the growth media restored CT production in the nqrA-F mutant, suggesting that decreased CT production in the Na+-NQR mutant is dependent on electron transport chain (ETC) activity. This notion was supported by the observations that two chemical inhibitors, a Na+-NQR specific inhibitor 2-n-Heptyl-4-hydroxyquinoline N-oxide (HQNO) and a succinate dehydrogenase (SDH) inhibitor, thenoyltrifluoroacetone (TTFA), strongly inhibited CT production in both classical and El Tor biotype strains of V. cholerae. Accordingly, we propose the main respiratory enzyme of V. cholerae, as a potential drug target to treat cholera because human mitochondria do not contain Na+-NQR orthologs. PMID:24361395

  16. Intervention of Isomaltodextrin Mitigates Intestinal Inflammation in a Dextran Sodium Sulfate-Induced Mouse Model of Colitis via Inhibition of Toll-like Receptor-4.

    PubMed

    Majumder, Kaustav; Fukuda, Toshihiko; Zhang, Hua; Sakurai, Takeo; Taniguchi, Yoshifumi; Watanabe, Hikaru; Mitsuzumi, Hitoshi; Matsui, Toshiro; Mine, Yoshinori

    2017-02-01

    Isomaltodextrin (IMD), a highly branched α-glucan, is a type of resistant starch. Earlier studies have indicated that polysaccharides could prevent inflammation and can be effective in reducing the complications of chronic gastrointestinal diseases such as inflammatory bowel disease (IBD). Therefore, the aim of the present study was to evaluate the anti-inflammatory effect of IMD in dextran sodium sulfate (DSS)-induced colitis in a mouse model. IMD (0.5, 1.0, 2.5, and 5.0% (w/v)) was given orally for 23 days to female Balb/c mice, and then 5% DSS was administered to induce colitis (from day 15 onward to the end of the trial). IMD could not prevent DSS-induced weight loss or colon shortening. However, IMD could reduce inflammatory cytokines, TNF-α and IL-6, in the colon. Gene expression indicated the tendency of IMD to suppress pro-inflammatory cytokines IL-1β, MCP-1, and IL-17 and to increase an anti-inflammatory cytokine, IL-10. Further study revealed that the anti-inflammatory action of IMD mediates through inhibition of the expression of Toll-like receptor-4.

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

    PubMed

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

    2016-06-22

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

  18. Inhibition of the sodium-translocating NADH-ubiquinone oxidoreductase [Na+-NQR] decreases cholera toxin production in Vibrio cholerae O1 at the late exponential growth phase.

    PubMed

    Minato, Yusuke; Fassio, Sara R; Reddekopp, Rylan L; Häse, Claudia C

    2014-01-01

    Two virulence factors produced by Vibrio cholerae, cholera toxin (CT) and toxin-corregulated pilus (TCP), are indispensable for cholera infection. ToxT is the central regulatory protein involved in activation of CT and TCP expression. We previously reported that lack of a respiration-linked sodium-translocating NADH-ubiquinone oxidoreductase (Na(+)-NQR) significantly increases toxT transcription. In this study, we further characterized this link and found that Na(+)-NQR affects toxT expression only at the early-log growth phase, whereas lack of Na(+)-NQR decreases CT production after the mid-log growth phase. Such decreased CT production was independent of toxT and ctxB transcription. Supplementing a respiratory substrate, l-lactate, into the growth media restored CT production in the nqrA-F mutant, suggesting that decreased CT production in the Na(+)-NQR mutant is dependent on electron transport chain (ETC) activity. This notion was supported by the observations that two chemical inhibitors, a Na(+)-NQR specific inhibitor 2-n-Heptyl-4-hydroxyquinoline N-oxide (HQNO) and a succinate dehydrogenase (SDH) inhibitor, thenoyltrifluoroacetone (TTFA), strongly inhibited CT production in both classical and El Tor biotype strains of V. cholerae. Accordingly, we propose the main respiratory enzyme of V. cholerae, as a potential drug target to treat cholera because human mitochondria do not contain Na(+)-NQR orthologs.

  19. Rosmarinic acid suppresses colonic inflammation in dextran sulphate sodium (DSS)-induced mice via dual inhibition of NF-κB and STAT3 activation

    PubMed Central

    Jin, Bo-Ram; Chung, Kyung-Sook; Cheon, Se-Yun; Lee, Minho; Hwang, Soonjae; Noh Hwang, Sam; Rhee, Ki-Jong; An, Hyo-Jin

    2017-01-01

    Ulcerative colitis (UC), a type of inflammatory bowel disease (IBD), is a chronic inflammatory disorder of the colon. Although UC is generally treated with anti-inflammatory drugs or immunosuppressants, most of these treatments often prove to be inadequate. Rosmarinic acid (RA) is a phenolic ester included in various medicinal herbs such as Salvia miltiorrhiz and Perilla frutescens. Although RA has many biological and pharmacological activities, the anti-inflammatory effect of RA in colonic tissue remains unclear. In this study, we investigated the anti-inflammatory effects and underlying molecular mechanism of RA in mice with dextran sulphate sodium (DSS)-induced colitis. In the DSS-induced colitis model, RA significantly reduced the severity of colitis, as assessed by disease activity index (DAI) scores, colonic damage, and colon length. In addition, RA resulted in the reduction of the inflammatory-related cytokines, such as IL-6, IL-1β, and IL-22, and protein levels of COX-2 and iNOS in mice with DSS-induced colitis. Furthermore, RA effectively and pleiotropically inhibited nuclear factor-kappa B and signal transducer and activator of transcription 3 activation, and subsequently reduced the activity of pro-survival genes that depend on these transcription factors. These results demonstrate that RA has an ameliorative effect on colonic inflammation and thus a potential therapeutic role in colitis. PMID:28383063

  20. Acid-base properties of titanium-antimony oxides catalysts

    SciTech Connect

    Zenkovets, G.A.; Paukshtis, E.A.; Tarasova, D.V.; Yurchenko, E.N.

    1982-06-01

    The acid-base properties of titanium-antimony oxide catalysts were studied by the methods of back titration and ir spectroscopy. The interrelationship between the acid-base and catalytic properties in the oxidative ammonolysis of propylene was discussed. 3 figures, 1 table.

  1. Antimony(V) Adsorption by Variable-Charge Minerals

    DTIC Science & Technology

    2013-10-01

    Sb(OH)6, SO4, and PO4 adsorption by gibbsite , kaolinite , goethite, and birnessite...pKa triple layer surface complexation modeling of Sb(OH)6, SO4, and PO4 adsorption by gibbsite , kaolinite , goethite, and birnessite...Competition Surface Complexation Triple Layer Model Gibbsite Kaolinite Goethite Birnessite xviii Abstract Background. Antimony (Sb) is a

  2. Discovery of palladium, antimony, tellurium, iodine, and xenon isotopes

    SciTech Connect

    Kathawa, J.; Fry, C.; Thoennessen, M.

    2013-01-15

    Currently, thirty-eight palladium, thirty-eight antimony, thirty-nine tellurium, thirty-eight iodine, and forty xenon isotopes have been observed and the discovery of these isotopes is described here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.

  3. Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B

    PubMed Central

    Morizot, Gloria; Jouffroy, Romain; Faye, Albert; Chabert, Paul; Belhouari, Katia; Calin, Ruxandra; Charlier, Caroline; Miailhes, Patrick; Siriez, Jean-Yves; Mouri, Oussama; Yera, Hélène; Gilquin, Jacques; Tubiana, Roland; Lanternier, Fanny; Mamzer, Marie-France; Legendre, Christophe; Peyramond, Dominique; Caumes, Eric; Lortholary, Olivier; Buffet, Pierre

    2016-01-01

    We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure. PMID:26735920

  4. Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B.

    PubMed

    Morizot, Gloria; Jouffroy, Romain; Faye, Albert; Chabert, Paul; Belhouari, Katia; Calin, Ruxandra; Charlier, Caroline; Miailhes, Patrick; Siriez, Jean-Yves; Mouri, Oussama; Yera, Hélène; Gilquin, Jacques; Tubiana, Roland; Lanternier, Fanny; Mamzer, Marie-France; Legendre, Christophe; Peyramond, Dominique; Caumes, Eric; Lortholary, Olivier; Buffet, Pierre

    2016-01-01

    We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure.

  5. Antimony and arsenic biogeochemistry in the East China Sea

    NASA Astrophysics Data System (ADS)

    Ren, Jing-Ling; Zhang, Xu-Zhou; Sun, You-Xu; Liu, Su-Mei; Huang, Daji; Zhang, Jing

    2016-02-01

    The biogeochemical cycles of the metalloid elements arsenic and antimony in the East China Sea (ECS), one of the most important marginal seas for western Pacific, were examined in May 2011. Dissolved inorganic arsenic (As(V) and As(III)) and antimony (Sb(V) and Sb(III)) species were determined by selective hydride generation-atomic fluorescence spectrometry (HG-AFS). Results show that total dissolved inorganic arsenic (TDIAs; [TDIAs]=[As(V)]+[As(III)]) were moderately depleted in the surface water and enriched in the deep water. Arsenite (As(III)) showed different vertical profiles with that of TDIAs, with significant surface enrichment in the middle shelf region where the concentrations of phosphate were extremely low. Speciation of dissolved arsenic was subtly controlled by the stoichiometric molar ratio of arsenate (As(V)) to phosphate. The average As(V)/P ratio for the ECS in spring 2011 was 10.8×10-3, which is higher than previous results and indicates the arsenate stress. The concentrations of total dissolved inorganic antimony (TDISb; [TDISb]=[Sb(V)]+[Sb(III)]) were high near the Changjiang Estuary and the coastal area of Hangzhou Bay and decreased moderately off the coast. TDISb displayed moderate conservative behavior in the ECS that confirms by the correlations with salinity and dissolved aluminum. Different with that of As(III), antimonite (Sb(III)) concentrations were extremely lower in the ECS, with relative higher concentration appeared at the bottom layer which indicates the contribution from sediment-water interface. A preliminary box model was established to estimate the water-mass balance and antimony budgets for the ECS. Compared with other areas in the world, the concentrations of dissolved inorganic arsenic and antimony in the ECS remain at natural levels.

  6. Whitening effect by stain inhibition from a chewing gum with sodium hexametaphosphate in a controlled twelve-week single-blind trial.

    PubMed

    Porciani, Pier Francesco; Grandini, Simone; Perra, Caterina; Grandini, Romano

    2006-01-01

    A twelve-week clinical study was conducted to assess the effect of a chewing gum containing sodium hexametaphosphate (4%) on the inhibition of stain formation. Fifty-four subjects were entered and completed all aspects of the study. Twenty-seven of the subjects were smokers, and the other half did not smoke. Subjects were randomly assigned to the test gum or no-gum group. Each participant received a full oral prophylaxis at the beginning of each period of observation. Those chewing the test gum agreed to chew four times a day, for five minutes each time, over twelve weeks. Those assigned to the no-gum group agreed not to chew any gum. After twelve weeks, participants were scored for stain deposits (Lobene Index), received a second oral prophylaxis, and joined the alternate group in this cross-over format. At the end of the twenty-fourth week, all subjects were again scored for stain deposits and the study was completed. In order to enhance stain formation during the entire 24-week study period, all participants received a supply of a chlorhexidine (0.12%) dentifrice without anionic agents to use three times a day. Stain levels were scored by the same examiner for all measurements and recorded on computer. The examiner was blinded to all treatment assignments. There were no reported problems associated with the chewing gum. The Lobene Index mean score for stain extent was 0.54 +/- 0.36) in the test-gum group and 0.81 +/- 0.47) for the no-gum group. The difference between the mean scores was highly significant with paired sample t-test (p < 0.001). Mean stain intensity was 0.57 +/- 0.38) in the test group and 0.95 (+/- 0.72) in the control group, with a statistically significant difference at p < 0.01. The results indicated that chewing gum containing sodium hexametaphosphate reduced induced stain formation by 33% compared to a no-gum treatment.

  7. Influence of combined pollution of antimony and arsenic on culturable soil microbial populations and enzyme activities.

    PubMed

    Wang, Qiongshan; He, Mengchang; Wang, Ying

    2011-01-01

    The effects of both combined and single pollution of antimony (Sb) and arsenic (As) in different concentrations on culturable soil microbial populations and enzyme activities were studied under laboratory conditions. Joint effects of both Sb and As were different from that of Sb or As alone. The inhibition rate of culturable soil microbial populations under Sb and As pollution followed the order: bacterial > fungi > actinomycetes. There existed antagonistic inhibiting effect on urease and acid phophatase and synergistic inhibiting effect on protease under the combined pollution of Sb (III) and As (III). Only urease appeared to be the most sensitive indicator under Sb (V) and As (V) pollution, and there existed antagonistic inhibiting effect on acid phophatase and synergistic inhibiting effect on urease and protease under Sb (V) and As (V) combined pollution at most time. In this study, we also confirmed that the trivalent states of Sb and As were more toxic to all the microbes tested and more inhibitory on microbial enzyme activities then their pentavalent counterparts. The results also suggest that not only the application rate of the two metalloids but also the chemical form of metalloids should be considered while assessing the effect of metalloid on culturable microbial populations and enzyme activities. Urease and acid phosphatase can be used as potential biomarkers to evaluate the intensity of Sb (III) and As (III) stress.

  8. Clinical and Parasitological Features of Patients with American Cutaneous Leishmaniasis that Did Not Respond to Treatment with Meglumine Antimoniate

    PubMed Central

    Robayo, Marta L.; Lopez, Myriam C.; Daza, Carlos D.; Bedoya, Angela; Mariño, Maria L.; Saavedra, Carlos H.

    2016-01-01

    Background American cutaneous leishmaniasis (ACL) is a complicated disease producing about 67.000 new cases per year. The severity of the disease depends on the parasite species; however in the vast majority of cases species confirmation is not feasible. WHO suggestion for ACL produced by Leishmania braziliensis, as first line treatment, are pentavalent antimonial derivatives (Glucantime or Sodium Stibogluconate) under systemic administration. According to different authors, pentavalent antimonial derivatives as treatment for ACL show a healing rate of about 75% and reasons for treatment failure are not well known. Methods In order to characterise the clinical and parasitological features of patients with ACL that did not respond to Glucantime, a cross-sectional observational study was carried out in a cohort of 43 patients recruited in three of the Colombian Army National reference centers for complicated ACL. Clinical and paraclinical examination, and epidemiological and geographic information were recorded for each patient. Parasitological, histopathological and PCR infection confirmation were performed. Glucantime IC50 and in vitro infectivity for the isolated parasites were estimated. Results Predominant infecting Leishmania species corresponds to L. braziliensis (95.4%) and 35% of the parasites isolated showed a significant decrease in in vitro Glucanatime susceptibility associated with previous administration of the medicament. Lesion size and in vitro infectivity of the parasite are negatively correlated with decline in Glucantime susceptibility (Spearman: r = (-)0,548 and r = (-)0,726; respectively). Conclusion A negative correlation between lesion size and parasite resistance is documented. L. braziliensis was found as the main parasite species associated to lesion of patients that underwent treatment failure or relapse. The indication of a second round of treatment in therapeutic failure of ACL, produced by L. braziliensis, with pentavalent antimonial

  9. Clinical and Parasitological Features of Patients with American Cutaneous Leishmaniasis that Did Not Respond to Treatment with Meglumine Antimoniate.

    PubMed

    Perez-Franco, Jairo E; Cruz-Barrera, Mónica L; Robayo, Marta L; Lopez, Myriam C; Daza, Carlos D; Bedoya, Angela; Mariño, Maria L; Saavedra, Carlos H; Echeverry, Maria C

    2016-05-01

    American cutaneous leishmaniasis (ACL) is a complicated disease producing about 67.000 new cases per year. The severity of the disease depends on the parasite species; however in the vast majority of cases species confirmation is not feasible. WHO suggestion for ACL produced by Leishmania braziliensis, as first line treatment, are pentavalent antimonial derivatives (Glucantime or Sodium Stibogluconate) under systemic administration. According to different authors, pentavalent antimonial derivatives as treatment for ACL show a healing rate of about 75% and reasons for treatment failure are not well known. In order to characterise the clinical and parasitological features of patients with ACL that did not respond to Glucantime, a cross-sectional observational study was carried out in a cohort of 43 patients recruited in three of the Colombian Army National reference centers for complicated ACL. Clinical and paraclinical examination, and epidemiological and geographic information were recorded for each patient. Parasitological, histopathological and PCR infection confirmation were performed. Glucantime IC50 and in vitro infectivity for the isolated parasites were estimated. Predominant infecting Leishmania species corresponds to L. braziliensis (95.4%) and 35% of the parasites isolated showed a significant decrease in in vitro Glucanatime susceptibility associated with previous administration of the medicament. Lesion size and in vitro infectivity of the parasite are negatively correlated with decline in Glucantime susceptibility (Spearman: r = (-)0,548 and r = (-)0,726; respectively). A negative correlation between lesion size and parasite resistance is documented. L. braziliensis was found as the main parasite species associated to lesion of patients that underwent treatment failure or relapse. The indication of a second round of treatment in therapeutic failure of ACL, produced by L. braziliensis, with pentavalent antimonial derivatives is discussable.

  10. Stimulation of cell division in the rat by NaCl, KCl, MgCl2, and CaCl2, and inhibition of the sodium chloride effect on the glandular stomach by ascorbic acid and beta-carotene.

    PubMed

    Lugli, S M; Lutz, W K

    1999-01-01

    Three questions associated with the stimulation of cell division by chloride salts have been investigated: (i) whether cations other than sodium show a similar effect, (ii) whether vitamins can have a preventive activity, and (iii) whether subchronic treatment with sodium chloride in the diet is also effective. Male Fischer 344 rats were given solutions of the chloride salts of sodium, potassium, magnesium, and calcium by oral gavage. Water was used for control. After 4 h, a 24-h osmotic minipump containing 5-bromo-2'-deoxyuridine was implanted subcutaneously. The forestomach and glandular stomach, as well as liver and bladder were analyzed immunohistochemically 24 h later for the proportion of cells in S phase as an indicator of the rate of replicative DNA synthesis. For both the forestomach and the glandular stomach, potassium was as potent as sodium, and the divalent cations Mg and Ca were even more potent on a molar basis. Supplementation of the diet with ascorbic acid (2 g/kg food) or beta-carotene (12.5 mg/kg food) for 1 week before gavage of the sodium chloride solution resulted in an inhibition of the stimulation of cell division. A putative tumor-chemopreventive activity of the two vitamins might therefore not only rely on their antioxidative properties but may include effects on the cell cycle. A 4-week treatment with a sodium chloride supplement in the diet (2% and 4% supplement) resulted in a significant stimulation of cell division not only in both parts of the stomach and in the bladder (with the 4% supplement) but also in the liver (even with the 2% supplement). Sodium-chloride-stimulated cell turnover therefore is a sustained effect.

  11. Resveratrol attenuates the Na(+)-dependent intracellular Ca(2+) overload by inhibiting H(2)O(2)-induced increase in late sodium current in ventricular myocytes.

    PubMed

    Qian, Chunping; Ma, Jihua; Zhang, Peihua; Luo, Antao; Wang, Chao; Ren, Zhiqiang; Kong, Linghao; Zhang, Shuo; Wang, Xiaojing; Wu, Ying

    2012-01-01

    Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H(2)O(2))-induced increase in late sodium current (I(Na.L)) which augmented the reverse Na(+)-Ca(2+) exchanger current (I(NCX)), and the diastolic intracellular Ca(2+) concentration in ventricular myocytes. I(Na.L), I(NCX,) L-type Ca(2+) current (I(Ca.L)) and intracellular Ca(2+) properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix), respectively, in rabbit ventricular myocytes. Resveratrol (10, 20, 40 and 80 µM) decreased I(Na.L) in myocytes both in the absence and presence of H(2)O(2) (300 µM) in a concentration dependent manner. Ranolazine (3-9 µM) and tetrodotoxin (TTX, 4 µM), I(Na.L) inhibitors, decreased I(Na.L) in cardiomyocytes in the presence of 300 µM H(2)O(2). H(2)O(2) (300 µM) increased the reverse I(NCX) and this increase was significantly attenuated by either 20 µM resveratrol or 4 µM ranolazine or 4 µM TTX. In addition, 10 µM resveratrol and 2 µM TTX significantly depressed the increase by 150 µM H(2)O(2) of the diastolic intracellular Ca(2+) fura-2 fluorescence intensity (FFI), fura-fluorescence intensity change (△FFI), maximal velocity of intracellular Ca(2+) transient rise and decay. As expected, 2 µM TTX had no effect on I(Ca.L). Resveratrol protects the cardiomyocytes by inhibiting the H(2)O(2)-induced augmentation of I(Na.L.)and may contribute to the reduction of ischemia-induced lethal arrhythmias.

  12. Resveratrol Attenuates the Na+-Dependent Intracellular Ca2+ Overload by Inhibiting H2O2-Induced Increase in Late Sodium Current in Ventricular Myocytes

    PubMed Central

    Qian, Chunping; Ma, Jihua; Zhang, Peihua; Luo, Antao; Wang, Chao; Ren, Zhiqiang; Kong, Linghao; Zhang, Shuo; Wang, Xiaojing; Wu, Ying

    2012-01-01

    Background/Aims Resveratrol has been demonstrated to be protective in the cardiovascular system. The aim of this study was to assess the effects of resveratrol on hydrogen peroxide (H2O2)-induced increase in late sodium current (INa.L) which augmented the reverse Na+-Ca2+ exchanger current (INCX), and the diastolic intracellular Ca2+ concentration in ventricular myocytes. Methods INa.L, INCX, L-type Ca2+ current (ICa.L) and intracellular Ca2+ properties were determined using whole-cell patch-clamp techniques and dual-excitation fluorescence photomultiplier system (IonOptix), respectively, in rabbit ventricular myocytes. Results Resveratrol (10, 20, 40 and 80 µM) decreased INa.L in myocytes both in the absence and presence of H2O2 (300 µM) in a concentration dependent manner. Ranolazine (3–9 µM) and tetrodotoxin (TTX, 4 µM), INa.L inhibitors, decreased INa.L in cardiomyocytes in the presence of 300 µM H2O2. H2O2 (300 µM) increased the reverse INCX and this increase was significantly attenuated by either 20 µM resveratrol or 4 µM ranolazine or 4 µM TTX. In addition, 10 µM resveratrol and 2 µM TTX significantly depressed the increase by 150 µM H2O2 of the diastolic intracellular Ca2+ fura-2 fluorescence intensity (FFI), fura-fluorescence intensity change (△FFI), maximal velocity of intracellular Ca2+ transient rise and decay. As expected, 2 µM TTX had no effect on ICa.L. Conclusion Resveratrol protects the cardiomyocytes by inhibiting the H2O2-induced augmentation of INa.L.and may contribute to the reduction of ischemia-induced lethal arrhythmias. PMID:23272101

  13. Sodium phenylacetate inhibits the Ras/MAPK signaling pathway to induce reduction of the c-Raf-1 protein in human and canine breast cancer cells.

    PubMed

    Watanabe, Manabu; Miyajima, Nozomi; Igarashi, Maki; Endo, Yoshifumi; Watanabe, Natsuko; Sugano, Sumio

    2009-11-01

    An aromatic fatty acid, phenylacetate (PA), has been shown to have cytostatic, antitumor and cell differentiation-inducing effects on various kinds of tumors. Previously, we have demonstrated cell growth inhibition, malignant phenotype reduction and cell differentiation effects of sodium phenylacetate (NaPA) treatment in a canine mammary tumor cell line. To clarify the molecular mechanism of these effects, we examined the expression of Ras/MAPK signaling pathway-related molecules in human and canine breast cancer cell lines, and found that the level of c-Raf-1 protein was reduced by 5, 10 and 20 mM of NaPA treatments, though Ras activation was maintained. Dephosphorylation of c-Raf-1 at Serine (Ser) 259, Ser 338, and Ser 621 were also seen in NaPA-treated cells. Downstream factors in the pathway, such as mitogen-activated protein kinase/ERK kinase (MEK)1/2 and ERK1/2, showed decreased activity, and accordingly, expressions of cyclinD1, c-myc, and inactivation of p90 ribosomal S6 kinase (RSK), which are MAPK targets, were reduced. We also observed the reduction of cell-cycle-promoted molecules, such as cdc1/cdk2, cdk4, PCNA cyclin A, and cyclin B, and the increased expression of p27kip1. Furthermore, expression of an epithelial marker, E-cadherin, was increased by NaPA treatment. These results suggest that one of the molecular targets of NaPA treatment was the reduction of c-Raf-1 protein, and that its reduction results in the decrease of malignant characteristics of tumor cells through blockage of the Ras/MAPK signaling pathway.

  14. Randomized in vivo trial evaluating plaque inhibition benefits of an advanced stannous-containing sodium fluoride dentifrice used in conjunction with power brush technology

    PubMed Central

    Bellamy, PG; Boulding, A; Farmer, S; Day, TN; Barker, ML; Harris, R; Mussett, AJ

    2014-01-01

    Objective To compare the plaque inhibition efficacy of a novel stannous-containing sodium fluoride test dentifrice to a standard anticavity negative control dentifrice, when both were used in conjunction with an advanced oscillating–rotating (O/R) power toothbrush. Methods This was a randomized, two-treatment, three-period, double-blind crossover study conducted in a population using an O/R power brush. Subjects brushed twice per day with their assigned dentifrice during the three-treatment periods, each lasting for 17 consecutive days. Each period was separated by a 4-day washout period during which subjects continued to use their O/R power toothbrush. Plaque levels were assessed and averaged amongst three assessments taken on days 15, 16 and 17 at the end of each treatment period using digital plaque imaging analysis. Assessments were carried out on the facial anterior tooth surfaces in the morning before brushing (A.M. prebrush) following whole-mouth brushing (30 s per quadrant) with the assigned dentifrice (A.M. post-brush) and in the afternoon (P.M.). Results Twenty-seven subjects were randomized and completed the study. During the 17-day usage period, the stannous-containing test NaF dentifrice demonstrated a statistically significant lower mean plaque area versus the negative control dentifrice at each assessment timepoint; overnight A.M. prebrush was 33.8% lower (P < 0.0001), A.M. post-brush was 21.8% lower (P < 0.01), and P.M. was 29.2% lower (P < 0.0001). Conclusion A population of O/R power toothbrush users had significantly less plaque coverage for all three measurements when using a stannous-containing NaF dentifrice than when using a negative control (fluoride) dentifrice. PMID:23844867

  15. Trans-Channel Interactions in Batrachotoxin-Modified Rat Skeletal Muscle Sodium Channels: Kinetic Analysis of Mutual Inhibition between μ-Conotoxin GIIIA Derivatives and Amine Blockers

    PubMed Central

    Ma, Quanli; Pavlov, Evgeny; Britvina, Tatiana; Zamponi, Gerald W.; French, Robert J.

    2008-01-01

    R13X derivatives of μ-conotoxin GIIIA bind externally to single sodium channels and block current incompletely with mean “blocked” durations of several seconds. We studied interactions between two classes of blockers (μ-conotoxins and amines) by steady state, kinetic analysis of block of BTX-modified Na channels in planar bilayers. The amines cause all-or-none block at a site internal to the selectivity filter. TPrA and DEA block single Na channels with very different kinetics. TPrA induces discrete, all-or-none, blocked events (mean blocked durations, ∼100 ms), whereas DEA produces a concentration-dependent reduction of the apparent single channel amplitude (“fast” block). These distinct modes of action allow simultaneous evaluation of block by TPrA and DEA, showing a classical, competitive interaction between them. The apparent affinity of TPrA decreases with increasing [DEA], based on a decrease in the association rate for TPrA. When an R13X μ-conotoxin derivative and one of the amines are applied simultaneously on opposite sides of the membrane, a mutually inhibitory interaction is observed. Dissociation constants, at +50 mV, for TPrA (∼4 mM) and DEA (∼30 mM) increase by ∼20%–50% when R13E (nominal net charge, +4) or R13Q (+5) is bound. Analysis of the slow blocking kinetics for the two toxin derivatives showed comparable decreases in affinity of the μ-conotoxins in the presence of an amine. Although this mutual inhibition seems to be qualitatively consistent with an electrostatic interaction across the selectivity filter, quantitative considerations raise questions about the mechanistic details of the interaction. PMID:18658223

  16. Saikosaponin a Mediates the Anticonvulsant Properties in the HNC Models of AE and SE by Inhibiting NMDA Receptor Current and Persistent Sodium Current

    PubMed Central

    Yu, Yun-Hong; Xie, Wei; Bao, Yong; Li, Hui-Ming; Hu, San-Jue; Xing, Jun-Ling

    2012-01-01

    Epilepsy is one of the most common neurological disorders, yet its treatment remains unsatisfactory. Saikosaponin a (SSa), a triterpene saponin derived from Bupleurum chinensis DC., has been demonstrated to have significant antiepileptic activity in a variety of epilepsy models in vivo. However, the electrophysiological activities and mechanisms of the antiepileptic properties of SSa remain unclear. In this study, whole-cell current-clamp recordings were used to evaluate the anticonvulsant activities of SSa in the hippocampal neuronal culture (HNC) models of acquired epilepsy (AE) and status epilepticus (SE). Whole-cell voltage-clamp recordings were used to evaluate the modulation effects of SSa on NMDA-evoked current and sodium currents in cultured hippocampal neurons. We found that SSa effectively terminated spontaneous recurrent epileptiform discharges (SREDs) in the HNC model of AE and continuous epileptiform high-frequency bursts (SE) in the HNC model of SE, in a concentration-dependent manner with an IC50 of 0.42 µM and 0.62 µM, respectively. Furthermore, SSa significantly reduced the peak amplitude of NMDA-evoked current and the peak current amplitude of INaP. These results suggest for the first time that the inhibitions of NMDA receptor current and INaP may be the underlying mechanisms of SSa’s anticonvulsant properties, including the suppression of SREDs and SE in the HNC models of AE and SE. In addition, effectively abolishing the refractory SE implies that SSa may be a potential anticonvulsant candidate for the clinical treatment of epilepsy. PMID:23209812

  17. Perchlorate transport and inhibition of the sodium iodide symporter measured with the yellow fluorescent protein variant YFP-H148Q/I152L

    SciTech Connect

    Cianchetta, Stefano; Bernardo, Julie di; Romeo, Giovanni; Rhoden, Kerry J.

    2010-03-15

    Perchlorate is an environmental contaminant that impairs thyroid function by interacting with the sodium iodide symporter (NIS), the transporter responsible for iodide uptake in the thyroid gland. Perchlorate is well known as a competitive inhibitor of iodide transport by NIS, and recent evidence demonstrates that NIS can also transport perchlorate. In this study, we evaluated the yellow fluorescent protein (YFP) variant YFP-H148Q/I152L, as a genetically encodable biosensor of intracellular perchlorate concentration monitored by real-time fluorescence microscopy. Fluorescence of recombinant YFP-H148Q/I152L was suppressed by perchlorate and iodide with similar affinities of 1.2 mM and 1.6 mM, respectively. Perchlorate suppressed YFP-H148Q/I152L fluorescence in FRTL-5 thyroid cells and NIS-expressing COS-7 cells, but had no effect on COS-7 cells lacking NIS. Fluorescence changes in FRTL-5 cells were Na{sup +}-dependent, consistent with the Na{sup +}-dependence of NIS activity. Perchlorate uptake in FRTL-5 cells resulted in 10-fold lower intracellular concentrations than iodide uptake, and was characterized by a higher affinity (K{sub m} 4.6 muM for perchlorate and 34.8 muM for iodide) and lower maximal velocity (V{sub max} 6.8 muM/s for perchlorate and 39.5 muM/s for iodide). Perchlorate also prevented iodide-induced changes in YFP-H148Q/I152L fluorescence in FRTL-5 cells, with half-maximal inhibition occurring at 1.1-1.6 muM. In conclusion, YFP-H148Q/I152L detects perchlorate accumulation by thyroid and other NIS-expressing cells, and reveals differences in the kinetics of perchlorate versus iodide transport by NIS.

  18. Tumor growth inhibition, apoptosis, and Bcl-2 down-regulation of MCF-7ras tumors by sodium phenylacetate and tamoxifen combination.

    PubMed

    Adam, L; Crépin, M; Isräel, L

    1997-03-15

    We demonstrated previously the antitumoral and antiproliferative effects of sodium phenylacetate (NaPA) on malignant breast epithelial MCF-7ras cells and its lack of toxicity. The present in vivo protocols were as follows: (1) a control group; (2) a NaPA-receiving group (450 mg/kg) through s.c. osmotic pumps (ALZA Corp.) for 2 weeks, followed by 2 weeks with no treatment; and (3) a tamoxifen (TAM)-receiving group (20 mg/kg two times per week). The second group was further divided as follows: (a) a group receiving same doses of NaPA; (b) a TAM-receiving group; and (c) a group receiving both NaPA and TAM. Although tumors treated by TAM alone (group 3) showed progressive regrowth after 6 weeks, indicating an escape from antiestrogen inhibition, the TAM-administered group, following 2 weeks of NaPA pretreatment (group 2b), showed significant tumor regression of about 40% after 8 weeks. This effect was amplified to over 60% (P < 0.001) by simultaneous administration of the two drugs (group 2c). The last group displayed about 30% apoptotic-like nuclei, together with lower proliferation index, and less tumor vascularization, as compared to less than 5% terminal deoxytransferase-mediated dUTP-X nick end labeling-positive nuclei, highly vascularized tumors, in the TAM-treated group. Furthermore, in vitro administration of 4-OH-tamoxifen induced a Bcl-2 up-regulation in MCF-7ras cells, which was completely abolished by NaPA pretreatment. The combination of NaPA and OHT induced significant cell differentiation with cell cycle accumulation in the G0-G1 phase.

  19. Sodium phenylacetate induces growth inhibition and Bcl-2 down-regulation and apoptosis in MCF7ras cells in vitro and in nude mice.

    PubMed

    Adam, L; Crépin, M; Savin, C; Israël, L

    1995-11-15

    Using a highly tumorigenic human breast cancer model (Ha-ras-transfected MCF7 cell line) we analyzed the efficacy of the differentiation-inducing agent sodium phenylacetate (NaPA), both in vitro and in vivo. NaPA-treated MCF7ras cells showed dose-dependent growth inhibition from 2.5 to 15 mM without apparent toxicity. Western blot analysis showed a Bcl-2 down-regulation after 48 h treatment with 5 mM NaPA, together with apparition of apoptotic nuclei by DAPI staining. Mice bearing MCF7ras xenografts (n = 40) were treated for 2 weeks through s.c.-delivering osmotic pumps, followed by 6 weeks of daily i.p. NaPA administration. After 3 weeks, the treated tumors showed growth arrest without regression for the whole observation time, e.g., 12 weeks. Immunohistochemical analysis showed Bcl-2 down-regulation and differentiation patterns: decrease of Ki-67 and increase of steroid receptors (estrogen and progesterone receptors) compared to controls. Cells cultured from treated tumors (II.b) displayed pseudotrabecular disposition as MCF7ras cells treated in vitro. They also showed a higher NaPA sensitivity, together with 70% Bcl-2 down-regulation as compared to the derived cells of untreated tumors (II.a). When reinjected into nude mice, II.b cells induced only one poorly vascularized, noninvasive tumor (8%) with lower proliferation index, 100% progesterone receptor positive cells, and 35% terminal deoxynucleotidyltransferase-mediated dUTP-X nick end labeling (+) nuclei, as compared to 100% induction of highly vascularized and invasive tumors with 3% terminal deoxynucleotidyltransferase-mediated dUTP-X nick end labeling (+) nuclei induced by II.a cells.

  20. Inhibition of dextran sulfate sodium (DSS)-induced intestinal inflammation via enhanced IL-10 and TGF-beta production by galectin-9 homologues isolated from intestinal parasites.

    PubMed

    Kim, Joo-Young; Cho, Min Kyoung; Choi, Seon Hee; Lee, Keun Hee; Ahn, Soon Cheol; Kim, Dong-Hee; Yu, Hak Sun

    2010-11-01

    We isolated a galectin-9 (Gal-9) homologue gene (Tl-gal) from an adult worm of the canine gastrointestinal nematode parasite, Toxascaris leonina, via random cDNA library sequencing. The deduced amino acid sequence of the Tl-gal genes evidenced an identity of 89% with the galectin of Dirofilaria immitis, 87% identity with the galectin of Brugia malayi, and 35% identity with the human GAL-9 gene. To evaluate immune modulate function of Tl-GAL in host inflammatory response, we constructed recombinant Tl-GAL (rTl-GAL) using an Escherichia coli expression vector system and treated to intestinal inflammation mice. Although the carbohydrate-binding ability of rTl-GAL was less than that of rat galectin, we confirmed that recombinant rTl-GAL has carbohydrate-binding activity. The clinical symptoms of dextran sulfate sodium (DSS)-treated mice after rTl-GAL pre-treatment were found to be minimized, or less profound, as compared to those of the rTl-GAL untreated group. Additionally, the DSS-treated mice exhibited a significant shortening of the colon, but the large intestines of the rTl-GAL pre-treated mice were longer than those of the control group (P<0.05). Additionally, the rTl-GAL treated group exhibited significantly increased the levels of TGF-beta and IL-10 (P<0.05). The production of these regulatory cytokines may ameliorate intestinal inflammation. These findings demonstrate that rTl-GAL could inhibit inflammation reactions via the inhibition of Th1 and Th2 cytokine production by increasing the production of TGF-beta and IL-10 cytokines. The rTl-GAL may induce TGF-beta expression, primarily via the activation of the p38 pathway. In conclusion, rTl-GAL may function like a host galectin, thus functioning as a regulatory molecule in the host immune system; rTl-GAL may prove useful in the design of novel therapeutic intervention strategies for the treatment of allergic and immune diseases.