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Sample records for disodium succinoyl glycyrrhetinate

  1. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Disodium EDTA. 172.135 Section 172.135 Food and... Preservatives § 172.135 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace-tate... following foods at not to exceed the levels prescribed, calculated as anhydrous calcium disodium EDTA:...

  2. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Disodium EDTA. 172.135 Section 172.135 Food and... Preservatives § 172.135 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace-tate... following foods at not to exceed the levels prescribed, calculated as anhydrous calcium disodium EDTA:...

  3. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Disodium EDTA. 573.360 Section 573.360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace-...

  4. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Disodium EDTA. 573.360 Section 573.360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace-...

  5. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Disodium EDTA. 573.360 Section 573.360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace-...

  6. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Disodium EDTA. 573.360 Section 573.360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace-...

  7. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Disodium EDTA. 172.135 Section 172.135 Food and... PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN CONSUMPTION Food Preservatives § 172.135 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace-tate) may be safely used in...

  8. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Disodium EDTA. 573.360 Section 573.360 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace-...

  9. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Calcium disodium EDTA. 172.120 Section 172.120... disodium EDTA. The food additive calcium disodium EDTA (calcium disodium ethylene-diaminetetraacetate) may.... 1 By weight of egg yolk portion. (2) With disodium EDTA (disodium ethylenediaminetetraacetate)...

  10. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Disodium phosphate. 582.6290 Section 582.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Disodium phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is...

  11. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Disodium phosphate. 582.6290 Section 582.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... Disodium phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is...

  12. Glycyrrhetinic acid-induced permeability transition in rat liver mitochondria.

    PubMed

    Salvi, Mauro; Fiore, Cristina; Armanini, Decio; Toninello, Antonio

    2003-12-15

    Glycyrrhetinic acid, a hydrolysis product of one of the main constituents of licorice, the triterpene glycoside of glycyrrhizic acid, when added to rat liver mitochondria at micromolar concentrations induces swelling, loss of membrane potential, pyridine nucleotide oxidation, and release of cytochrome c and apoptosis inducing factor. These changes are Ca(2+) dependent and are prevented by cyclosporin A, bongkrekic acid, and N-ethylmaleimide. All these observations indicate that glycyrrhetinic acid is a potent inducer of mitochondrial permeability transition and can trigger the pro-apoptotic pathway. PMID:14637195

  13. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Disodium phosphate. 182.6290 Section 182.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is generally recognized...

  14. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Disodium phosphate. 182.6290 Section 182.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR... phosphate. (a) Product. Disodium phosphate. (b) Conditions of use. This substance is generally recognized...

  15. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Disodium EDTA-copper. 73.2120 Section 73.2120 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The color additive disodium EDTA-copper is disodium ] (4-)-N,N′,O,O′,O N,O N′] cuprate (2-)....

  16. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false Disodium EDTA-copper. 73.2120 Section 73.2120 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The color additive disodium EDTA-copper is disodium ] (4-)-N,N′,O,O′,O N,O N′] cuprate (2-)....

  17. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Disodium EDTA-copper. 73.2120 Section 73.2120 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The color additive disodium EDTA-copper is disodium ] (4-)-N,N′,O,O′,O N,O N′] cuprate (2-)....

  18. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Calcium disodium EDTA. 172.120 Section 172.120... CONSUMPTION Food Preservatives § 172.120 Calcium disodium EDTA. The food additive calcium disodium EDTA... EDTA (disodium ethylenediaminetetraacetate) in the following foods at not to exceed, in...

  19. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Disodium EDTA-copper. 73.2120 Section 73.2120 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The color additive disodium EDTA-copper is disodium ] (4-)-N,N′,O,O′,O N,O N′] cuprate (2-)....

  20. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Calcium disodium EDTA. 172.120 Section 172.120... CONSUMPTION Food Preservatives § 172.120 Calcium disodium EDTA. The food additive calcium disodium EDTA... EDTA (disodium ethylenediaminetetraacetate) in the following foods at not to exceed, in...

  1. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Disodium EDTA-copper. 73.2120 Section 73.2120 Food... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The color additive disodium EDTA-copper is disodium ] (4-)-N,N′,O,O′,O N,O N′] cuprate (2-)....

  2. Sustainable production of valuable compound 3-succinoyl-pyridine by genetically engineering Pseudomonas putida using the tobacco waste.

    PubMed

    Wang, Weiwei; Xu, Ping; Tang, Hongzhi

    2015-01-01

    Treatment of solid and liquid tobacco wastes with high nicotine content remains a longstanding challenge. Here, we explored an environmentally friendly approach to replace tobacco waste disposal with resource recovery by genetically engineering Pseudomonas putida. The biosynthesis of 3-succinoyl-pyridine (SP), a precursor in the production of hypotensive agents, from the tobacco waste was developed using whole cells of the engineered Pseudomonas strain, S16dspm. Under optimal conditions in fed-batch biotransformation, the final concentrations of product SP reached 9.8 g/L and 8.9 g/L from aqueous nicotine solution and crude suspension of the tobacco waste, respectively. In addition, the crystal compound SP produced from aqueous nicotine of the tobacco waste in batch biotransformation was of high purity and its isolation yield on nicotine was 54.2%. This study shows a promising route for processing environmental wastes as raw materials in order to produce valuable compounds.

  3. Sustainable production of valuable compound 3-succinoyl-pyridine by genetically engineering Pseudomonas putida using the tobacco waste.

    PubMed

    Wang, Weiwei; Xu, Ping; Tang, Hongzhi

    2015-01-01

    Treatment of solid and liquid tobacco wastes with high nicotine content remains a longstanding challenge. Here, we explored an environmentally friendly approach to replace tobacco waste disposal with resource recovery by genetically engineering Pseudomonas putida. The biosynthesis of 3-succinoyl-pyridine (SP), a precursor in the production of hypotensive agents, from the tobacco waste was developed using whole cells of the engineered Pseudomonas strain, S16dspm. Under optimal conditions in fed-batch biotransformation, the final concentrations of product SP reached 9.8 g/L and 8.9 g/L from aqueous nicotine solution and crude suspension of the tobacco waste, respectively. In addition, the crystal compound SP produced from aqueous nicotine of the tobacco waste in batch biotransformation was of high purity and its isolation yield on nicotine was 54.2%. This study shows a promising route for processing environmental wastes as raw materials in order to produce valuable compounds. PMID:26574178

  4. Sustainable production of valuable compound 3-succinoyl-pyridine by genetically engineering Pseudomonas putida using the tobacco waste

    PubMed Central

    Wang, Weiwei; Xu, Ping; Tang, Hongzhi

    2015-01-01

    Treatment of solid and liquid tobacco wastes with high nicotine content remains a longstanding challenge. Here, we explored an environmentally friendly approach to replace tobacco waste disposal with resource recovery by genetically engineering Pseudomonas putida. The biosynthesis of 3-succinoyl-pyridine (SP), a precursor in the production of hypotensive agents, from the tobacco waste was developed using whole cells of the engineered Pseudomonas strain, S16dspm. Under optimal conditions in fed-batch biotransformation, the final concentrations of product SP reached 9.8 g/L and 8.9 g/L from aqueous nicotine solution and crude suspension of the tobacco waste, respectively. In addition, the crystal compound SP produced from aqueous nicotine of the tobacco waste in batch biotransformation was of high purity and its isolation yield on nicotine was 54.2%. This study shows a promising route for processing environmental wastes as raw materials in order to produce valuable compounds. PMID:26574178

  5. Analysis of Genes for Succinoyl Trehalose Lipid Production and Increasing Production in Rhodococcus sp. Strain SD-74

    PubMed Central

    Inaba, Tomohiro; Tokumoto, Yuta; Miyazaki, Yusuke; Inoue, Naoyuki; Maseda, Hideaki; Nakajima-Kambe, Toshiaki; Uchiyama, Hiroo

    2013-01-01

    Succinoyl trehalose lipids (STLs) are promising glycolipid biosurfactants produced from n-alkanes that are secreted by Rhodococcus species bacteria. These compounds not only exhibit unique interfacial properties but also demonstrate versatile biochemical actions. In this study, three novel types of genes involved in the biosynthesis of STLs, including a putative acyl coenzyme A (acyl-CoA) transferase (tlsA), fructose-bisphosphate aldolase (fda), and alkane monooxygenase (alkB), were identified. The predicted functions of these genes indicate that alkane metabolism, sugar synthesis, and the addition of acyl groups are important for the biosynthesis of STLs. Based on these results, we propose a biosynthesis pathway for STLs from alkanes in Rhodococcus sp. strain SD-74. By overexpressing tlsA, we achieved a 2-fold increase in the production of STLs. This study advances our understanding of bacterial glycolipid production in Rhodococcus species. PMID:24038682

  6. 21 CFR 172.535 - Disodium inosinate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... additive is the disodium salt of inosinic acid, manufactured and purified so as to contain no more than 150... of water of crystallization. (b) The food additive is used as a flavoring adjuvant in food....

  7. 21 CFR 172.535 - Disodium inosinate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... additive is the disodium salt of inosinic acid, manufactured and purified so as to contain no more than 150... of water of crystallization. (b) The food additive is used as a flavoring adjuvant in food....

  8. Enhanced biological phosphorus removal employing EDTA disodium

    SciTech Connect

    Bojinova, D.; Velkova, R.

    1996-12-31

    The biological phosphorus removal is a promising alternative to the conventional chemical technologies for processing of phosphate raw materials. The object of this study was the effect of EDTA disodium on the biotreatment of tunisian phosphorite with the strain of Aspergillus niger. The incubation was carried out in two nutritive mediums, with different phosphate content. The experimental results showed that the additives of EDTA disodium in the nutritive medium increased the rate of extraction of P{sub 2}O{sub 5} and shortened significantly the time for biological leaching. 5 refs., 3 figs., 2 tabs.

  9. 21 CFR 172.530 - Disodium guanylate.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Disodium guanylate. 172.530 Section 172.530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD FOR HUMAN CONSUMPTION (CONTINUED) FOOD ADDITIVES PERMITTED FOR DIRECT ADDITION TO FOOD FOR HUMAN...

  10. Chemical modifications of natural triterpenes - glycyrrhetinic and boswellic acids: evaluation of their biological activity

    PubMed Central

    Subba Rao, G. S. R.; Kondaiah, Paturu; Singh, Sanjay K.; Ravanan, Palaniyandi; Sporn, Michael B.

    2008-01-01

    Synthetic analogues of naturally occurring triterpenoids; glycyrrhetinic acid, arjunolic acid and boswellic acids, by modification of A-ring with a cyano- and enone- functionalities, have been reported. A novel method of synthesis of α-cyanoenones from isoxazoles is reported. Bio-assays using primary mouse macrophages and tumor cell lines indicate potent anti-inflammatory and cytotoxic activities associated with cyanoenones of boswellic acid and glycyrrhetinic acid. PMID:20622928

  11. Involvement of BID translocation in glycyrrhetinic acid and 11-deoxy glycyrrhetinic acid-induced attenuation of gastric cancer growth.

    PubMed

    Lin, Dejian; Zhong, Wei; Li, Juan; Zhang, Bing; Song, Gang; Hu, Tianhui

    2014-01-01

    Glycyrrhetinic acid (GA), the main chemical constituents of licorice, has shown remarkable anticancer activity. However, the side effects limit its widespread use. 11-DOGA is produced through reduction of GA 11-carbonyl to 11-hydroxyl to reduce its side effects, although its anticancer activities are largely unknown. Here, we report that the functional mechanisms of GA and 11-DOGA in gastric cancers, as well as the comparison between these two drugs' pharmacological potential. Firstly, we found that GA and 11-DOGA significantly inhibits the viabilities of gastric cancer cells in dose- and time-dependent manners. Both GA and 11-DOGA induce gastric cancer cells apoptosis and cell cycle arrest in G2 phase by upregulation of p21 and downregulation of cdc2 and cyclin B1. Further studies show that GA and 11-DOGA-induced apoptosis in gastric cancer cells is associated with BID translocation from nucleus to mitochondria. Moreover, GA and 11-DOGA could effectively inhibit tumor formation of gastric cancer cells in nude mice. Comparing with 11-DOGA, GA presents higher toxicity toward gastric cancer cells both in vivo and in vitro. Thus, the elucidation of the functional mechanisms of GA and 11-DOGA-induced attenuation of gastric cancer growth suggests a possible therapeutic role of GA and its derivatives.

  12. New drug, fospropofol disodium: a propofol prodrug.

    PubMed

    Welliver, Mark; Rugari, Susan M

    2009-08-01

    The use of propofol presents chemical and clinical concerns, including pain on injection, allergy risks, possible bacteria growth, and hyperlipidemia. These concerns have encouraged the search for alternative propofol formulations. Elimination of the soybean oil and lecithin carrier agents is difficult because the highly lipophilic diisopropyl phenol molecule does not dissolve in water. Propofol in aqueous solution would be a preferable alternative to lipid-based emulsions. One formulation of propofol is fospropofol disodium (Lusedra, Eisai Corporation of North America, Woodcliff Lake, New Jersey), previously known as Aquavan (MGI Pharma, Bloomington, Minnesota). Fospropofol is an aqueous solution of a propofol prodrug intended for injection. The discovery and development of this drug may address the concerns with the current propofol emulsion formulations while offering altered pharmacokinetics and pharmacodynamics for sedation. The structure, pharmacokinetics, pharmacodynamics, clinical studies, clinical applications, and implications are discussed. PMID:19731849

  13. The mechanism of hydrothermal hydrolysis for glycyrrhizic acid into glycyrrhetinic acid and glycyrrhetinic acid 3-O-mono-β-D-glucuronide in subcritical water.

    PubMed

    Fan, Rui; Li, Nan; Xu, Honggao; Xiang, Jun; Wang, Lei; Gao, Yanxiang

    2016-01-01

    To improve the bioactivity and sweetness properties of glycyrrhizic acid (GL), the hydrothermal hydrolysis of GL into glycyrrhetinic acid (GA) and glycyrrhetinic acid 3-O-mono-β-D-glucuronide (GAMG) in subcritical water was investigated. The effects of temperature, time and their interaction on the conversion ratios were analyzed and the reactions were elaborated with kinetics and thermodynamics. The results showed that GL hydrothermal hydrolysis was significantly (P < 0.05) affected by reaction time and temperature, as well as their interaction, and could be fitted into first-order kinetics. The thermodynamic analysis indicated that the hydrolysis of GL was endergonic and non-spontaneous. The hydrolytic pathways were composed of complex consecutive and parallel reactions. It was concluded that subcritical water may be a potential medium for producing GAMG and GA.

  14. Glycyrrhetinic acid-poly(ethylene glycol)-glycyrrhetinic acid tri-block conjugates based self-assembled micelles for hepatic targeted delivery of poorly water soluble drug.

    PubMed

    Wu, Fengbo; Xu, Ting; Liu, Chi; Chen, Can; Song, Xiangrong; Zheng, Yu; He, Gu

    2013-01-01

    The triblock 18β-glycyrrhetinic acid-poly(ethylene glycol)18β-glycyrrhetinic acid conjugates (GA-PEG-GA) based self-assembled micelles were synthesized and characterized by FTIR, NMR, transmission electron microscopy, and particle size analysis. The GA-PEG-GA conjugates having the critical micelle concentration of 6 × 10(-5) M were used to form nanosized micelles, with mean diameters of 159.21 ± 2.2 nm, and then paclitaxel (PTX) was incorporated into GA-PEG-GA micelles by self-assembly method. The physicochemical properties of the PTX loaded GA-PEG-GA micelles were evaluated including in vitro cellular uptake, cytotoxicity, drug release profile, and in vivo tissue distribution. The results demonstrate that the GA-PEG-GA micelles had low cytotoxicity and good ability of selectively delivering drug to hepatic cells in vitro and in vivo by the targeting moiety glycyrrhetinic acid. In conclusion, the GA-PEG-GA conjugates have potential medical applications for targeted delivery of poor soluble drug delivery.

  15. Determination of 18 beta-glycyrrhetinic acid in human serum using the fully automated ALCA-system.

    PubMed

    Heilmann, P; Heide, J; Schöneshöfer, M

    1997-07-01

    We report a method for the determination of 18 beta-glycyrrhetinic acid (glycyrrhetinic acid) in human serum using the ALCA-system. The technology of the ALCA-system is based on the principles of adsorptive and desorptive processes between liquid and solid phases. The assay is run fully automated and selective. Procedural losses throughout the analysis are negligible, thereby allowing for external calibration. The calibration curve is linear up to 10 mg/l and concentrations as low as 10 micrograms/l are detectable. CV is 2.5% for within- and 7.5% for between-assay precision at a level of 50 micrograms/l and 1.2% for within- and 8.5% for between-assay precision at a level of 500 micrograms/l. Specific and expensive reagents are not necessary and time-consuming manual operations are not involved. This assay can be selected from a wide spectrum of methods at any time. Thus, the present method is well-suited for drug monitoring purposes in the routine laboratory. In a pharmacokinetic study we measured serum levels of glycyrrhetinic acid in ten healthy young volunteers after ingestion of 500 mg glycyrrhetinic acid. Maximum levels of glycyrrhetinic acid were 6.3 mg/l 2 to 4 hours after ingestion. Twenty-four (24) hours after ingestion seven probands still had glycyrrhetinic acid levels above the detection limit with a mean level of 0.33 mg/l.

  16. The effects of disodium cromoglycate on dexamethasome metabolism.

    PubMed

    Brooks, S M; Sholiton, L J; Altenau, P

    1976-12-01

    The effect of disodium cromoglycate on dexamethasone metabolism was studied in 4 patients with bronchial asthma before and after 3 weeks of treatment. Labeled dexamethasome was injected intravenously and serial blood samples were collected during the next 6 hours. Transport kinetics of labeled dexamethasone were determined using a 2-compartment model. Baseline plasma equilibrated half-life values ranged from 133 to 258 min, and metabolic clearance rate ranged from 134 to 912 liter per day. After disodium cromoglycate therapy a small decrease in labeled dexamethasone clearance occurred. There was a mean increase in half-life of 20 min (9 per cent), being 201+/-51 (mean +/- SD) before therapy and 220+/-57 min after therapy. This was not significant. Metabolic clearance rate decreased 13 per cent (59 liter per day), being 441+/-334 liter per day before and 382+/-304 liter per day after treatment (P less than 0.05). Other transport kinetics of labeled dexamethasone were not significantly different with therapy. The results of this investigation demonstrate that disodium cromoglycate produces small but probably not significant changes in dexamethasone metabolism. The investigation supports the thesis that the steroid-sparing effect of disodium cromoglycate is not the result of depression of corticosteroid plasma clearance with longer duration of steroid action but most likely is the result of the effect of disodium cromoglycate on cellular mechanisms and inhibition of mediator release.

  17. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  18. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  19. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  20. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  1. 40 CFR 721.7000 - Polymer of disodium maleate, allyl ether, and ethylene oxide.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polymer of disodium maleate, allyl... New Uses for Specific Chemical Substances § 721.7000 Polymer of disodium maleate, allyl ether, and... substance identified generically as a polymer of disodium maleate, allyl ether, and ethylene oxide...

  2. Synthesis and Pro-Apoptotic Activity of Novel Glycyrrhetinic Acid Derivatives

    PubMed Central

    Logashenko, Evgeniya B; Salomatina, Oksana V; Markov, A V; Korchagina, Dina V; Salakhutdinov, Nariman F; Tolstikov, Genrikh A; Vlassov, Valentin V; Zenkova, Marina A

    2011-01-01

    Triterpenoids are used for medicinal purposes in many countries. Some, such as oleanolic and glycyrrhetinic acids, are known to be anti-inflammatory and anticarcinogenic. However, the biological activities of these naturally occurring molecules against their particular targets are weak, so the synthesis of new synthetic analogues with enhanced potency is needed. By combining modifications to both the A and C rings of 18βH-glycyrrhetinic acid, the novel synthetic derivative methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate was obtained. This derivative displays high antiproliferative activity in cancer cells, including a cell line with a multidrug-resistance phenotype. It causes cell death by inducing the intrinsic caspase-dependent apoptotic pathway. PMID:21328513

  3. Development and validation of a cost-effective, efficient, and robust liquid chromatographic method for the simultaneous determination of the acetyl and succinoyl content in hydroxypropyl methylcellulose acetate succinate polymer.

    PubMed

    Chen, Raymond; Sekulic, Sonja; Zelesky, Todd

    2002-01-01

    A reversed-phase liquid chromatographic method was developed and validated for the determination of the content of free acetic acid, free succinic acid, acetyl substituents, and succinoyl substituents in hydroxypropyl methylcellulose acetate succinate (HPMCAS; Chemical Abstracts Service Registry No. 71138-97-1) polymer. This single new method gave accurate and precise measurement of both acetyl and succinoyl substituents, which had previously required 3 Japanese Pharmaceutical Excipients (JPE) methods to accomplish. Consequently, analysis time and turnaround time are decreased significantly. Furthermore, this method can also separate and determine the free acetic and succinic acids in HPMCAS polymer, a task that the corresponding JPE method cannot achieve. The values for accuracy (average recovery from 12 standard samples) were 99.9% for acetic acid and 99.8% for succinic acid. The values for injection precision (relative standard deviation [RSD]) were 0.11% for acetic acid and 0.28% for succinic acid. The values for intermediate precision (RSD) were 1.25% for determination of the acetyl content at the 8.78% (w/w) level and 1.33% for determination of the succinoyl content at the 10.9% (w/w) level. The values for intermediate precision (RSD) were 5.98% for determination of free acetic acid at the 0.12% (w/w) level and 5.13% for determination of free succinic acid at the 0.029% (w/w) level. The method was proven to be robust with respect to variation in the pH of the mobile phase, the concentration of potassium dihydrogen phosphate, and the flow rate. The method is well suited for quality control in today's fast-paced pharmaceutical laboratories.

  4. Glycyrrhetinic acid, the active principle of licorice, can reduce the thickness of subcutaneous thigh fat through topical application.

    PubMed

    Armanini, Decio; Nacamulli, Davide; Francini-Pesenti, Francesco; Battagin, Giuliana; Ragazzi, Eugenio; Fiore, Cristina

    2005-07-01

    Cortisol is involved in the distribution and deposition of fat, and its action is regulated by the activity of 11beta-hydroxysteroid dehydrogenase. Glycyrrhetinic acid, the active principle of licorice root, blocks 11beta-hydroxysteroid dehydrogenase type 1, thus reducing the availability of cortisol at the level of adipocytes. We evaluated the effect of topical application of a cream containing glycyrrhetinic acid in the thickness of fat at the level of the thigh. Eighteen healthy women (age range 20-33 years) with normal BMI were randomly allocated to treatment, at the level of the dominant thigh, with a cream containing 2.5% glycyrrhetinic acid (n=9) or with a placebo cream containing the excipients alone (n=9). Before and after 1 month of treatment both the circumference and the thickness of the superficial fat layer of the thighs (by ultrasound analysis) were measured. The circumference and the thickness of the superficial fat layer were significantly reduced in comparison to the controlateral untreated thigh and to control subjects treated with the placebo cream. No changes were observed in blood pressure, plasma renin activity, plasma aldosterone or cortisol. The effect of glycyrrhetinic acid on the thickness of subcutaneous fat was likely related to a block of 11beta-hydroxysteroid dehydrogenase type 1 at the level of fat cells; therefore, glycyrrhetinic acid could be effectively used in the reduction of unwanted local fat accumulation. PMID:15894038

  5. Genotoxicity of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™).

    PubMed

    Nakano, Masahiko; Suzuki, Hiroshi; Imamura, Tadashi; Lau, Annette; Lynch, Barry

    2013-11-01

    The genotoxic potential of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) was evaluated in a battery of genotoxicity tests. The results of the bacterial mutation assay (Ames test) were negative. Weak positive results were obtained in 2 separate in vitro chromosomal aberration test in Chinese hamster lung (CHL) fibroblasts. Upon testing in an in vitro chromosomal aberration test in human peripheral blood lymphocytes, no genotoxic activity of PQQ was noted. In the in vivo micronucleus assay in mice, PQQ at doses up to 2,000 mg/kg body weight demonstrated that no genotoxic effects are expressed in vivo in bone marrow erythrocytes. The weak responses in the in vitro test CHL cells were considered of little relevance under conditions of likely human exposure. PQQ disodium was concluded to have no genotoxic activity in vivo.

  6. On the mechanism of mitochondrial permeability transition induction by glycyrrhetinic acid.

    PubMed

    Fiore, Cristina; Salvi, Mauro; Palermo, Mario; Sinigaglia, Giulietta; Armanini, Decio; Toninello, Antonio

    2004-10-01

    Glycyrrhetinic acid (GE), the aglycone of glycyrrhizic acid, a triterpene glycoside which represents one of the main constituents of licorice root, induces an oxidative stress in liver mitochondria responsible for the induction of membrane permeability transition. In fact, GE, by interacting with the mitochondrial respiratory chain, generates hydrogen peroxide which in turn oxidizes critical thiol groups and endogenous pyridine nucleotides leading to the opening of the transition pore. Most likely the reactive group of GE is the carbonyl oxygen in C-11 which, by interacting mainly with a Fe/S centre of mitochondrial complex I, generates an oxygen-centered radical responsible for the pro-oxidant action. PMID:15450957

  7. Study of an Acid-Free Technique for the Preparation of Glycyrrhetinic Acid from Ammonium Glycyrrhizinate in Subcritical Water.

    PubMed

    Lekar, Anna V; Borisenko, Sergey N; Vetrova, Elena V; Filonova, Olga V; Maksimenko, Elena V; Borisenko, Nikolai I; Minkin, Vladimir I

    2015-11-01

    The aim of this work was to study an application of a previously developed expedient acid-free technique for the preparation of glycyrrhetinic acid from ammonium glycyrrhizinate that requires no use of acids and toxic organic solvents. Subcritical water that serves as a reactant and a solvent was used in order to obtain glycyrrhetinic acid in good yields starting from ammonium glycyrrhizinate. It has been shown that variation of only one parameter of the process (temperature) allows alteration to thecomposition of the hydrolysis products. A new method was used for the synthesis of glycyrrhetinic acid (glycyrrhizic acid aglycone) and its monoglycoside. HPLC combined with mass spectrometry and NMR spectroscopy were used to determine the quantitative and qualitative compositions of the obtained products. The method developed for the production of glycyrrhetinic acid in subcritical water is environmentally friendly and faster than conventional hydrolysis methods that use acids and-expensive and toxic organic solvents. The proposed technique has a potential for the future development of inexpensive and environmentally friendly technologies for production of new pharmaceutical plant-based substances. PMID:26749800

  8. 40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...)-, disodium salt. 721.3820 Section 721.3820 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a)...

  9. 40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...)-, disodium salt. 721.3820 Section 721.3820 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a)...

  10. 40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...)-, disodium salt. 721.3820 Section 721.3820 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a)...

  11. 40 CFR 721.3820 - L-Glutamic acid, N-(1-oxododecyl)-, disodium salt.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...)-, disodium salt. 721.3820 Section 721.3820 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a)...

  12. Monosodium glutamate, disodium inosinate, disodium guanylate, lysine and taurine improve the sensory quality of fermented cooked sausages with 50% and 75% replacement of NaCl with KCl.

    PubMed

    dos Santos, Bibiana Alves; Campagnol, Paulo Cezar Bastianello; Morgano, Marcelo Antônio; Pollonio, Marise Aparecida Rodrigues

    2014-01-01

    Fermented cooked sausages were produced by replacing 50% and 75% of NaCl with KCl and adding monosodium glutamate, disodium inosinate, disodium guanylate, lysine and taurine. The manufacturing process was monitored by pH and water activity measurements. The sodium and potassium contents of the resulting products were measured. The color values (L*, a* and b*), texture profiles and sensory profiles were also examined. Replacing 50% and 75% NaCl with KCl depreciated the sensory quality of the products. The reformulated sausages containing monosodium glutamate combined with lysine, taurine, disodium inosinate and disodium guanylate masked the undesirable sensory attributes associated with the replacement of 50% and 75% NaCl with KCl, allowing the production of fermented cooked sausages with good sensory acceptance and approximately 68% sodium reduction. PMID:24008059

  13. Preparation and characterization of glycyrrhetinic acid-modified stearic acid-grafted chitosan micelles.

    PubMed

    Chen, Qian; Sun, Yong; Wang, Jiangjun; Yan, Guowen; Cui, Zhaoyuan; Yin, Hongli; Wei, Haitian

    2015-01-01

    Stearic acid-grafted chitosan (CS-SA) and glycyrrhetinic acid-conjugated stearic acid-grafted chitosan (GA-CS-SA) were synthesized and were further used for the preparation of micelles. The substitution degree (SD) of SA and GA on CS was measured. The physicochemical properties of CS-SA and GA-CS-SA micelles such as critical micelle concentration (CMC), aggregation number of hydrophobic micro-domain (AN), particle size, zeta potential, and morphology were also determined. The CMC of GA-CS-SA was about 17.49 μg/mL, which was relatively low. Its AN was 2.09. The GA-CS-SA micelles showed spherical shape with mean diameter of 121.1 nm and had positive charge, which suggested that GA-CS-SA could be a good carrier of cancer drug.

  14. In vitro effects of glycyrrhetinic acid on the growth of clinical isolates of Candida albicans.

    PubMed

    Pellati, Donatella; Fiore, Cristina; Armanini, Decio; Rassu, Mario; Bertoloni, Giulio

    2009-04-01

    Compounds derived from Glycyrrhiza glabra L. root have been used widely for centuries for their numerous therapeutic properties. The present study aimed to test the in vitro activity against Candida albicans strains of the compound 18-beta glycyrrhetinic acid (18-beta GA), derived from the root of Glycyrrhiza species. This antimicrobial activity was assessed using the National Committee for Clinical Laboratory Standards (NCCLS) method on C. albicans strains that were isolated from patients with recurrent vulvovaginal candidiasis (RVVC). The in vitro growth of the C. albicans strains was markedly reduced, in a pH-dependent manner, by relatively low doses (6.2 microg/mL) of 18-beta GA. The results demonstrate that 18-beta GA is a promising biological alternative for the topical treatment of recurrent vulvovaginal candidiasis (RVVC). PMID:19067381

  15. Mobilization and redistribution of lead over the course of calcium disodium ethylenediamine tetraacetate chelation therapy

    SciTech Connect

    Cory-Slechta, D.A.; Weiss, B.; Cox, C.

    1987-12-01

    After its successful application to the treatment of acute Pb poisoning, Ca disodium EDTA came into routine clinical use for diagnosis and treatment of subacute and chronic Pb poisoning. Despite widespread use, few definitive conclusions have emerged about the sources of Pb mobilized by Ca disodium EDTA. Furthermore, the possibility that mobilized Pb may be redistributed has been suggested. The current studies indicate that the standard therapeutic protocol for Ca disodium EDTA has little impact on critical organs such as brain and liver and moreover, that diagnostic Ca disodium EDTA chelation may even increase the concentration of Pb in these tissues. After a 3 to 4 month exposure to Pb acetate in drinking water, different groups of rats received daily i.p. injections of saline (control), 75 or 150 mg/kg of Ca disodium EDTA for either 1, 2, 3, 4 or 5 days and were then sacrificed 24 hr after the final injection. Tissue analyses indicated that Pb was mobilized from bone and kidney and redistributed initially to both brain and liver. Levels in both brain and liver declined with subsequent Ca disodium EDTA injections, but no net loss from either tissue occurred over the 5-day treatment period despite a decline in blood Pb levels and a marked enhancement of urinary Pb excretion. These findings stress the need for further investigation of Ca disodium EDTAs effects and for parallel evaluation of alternate chelating agents, and suggest that a re-evaluation of both the diagnostic and therapeutic roles of Ca disodium EDTA may be advisable.

  16. Effect of glycyrrhetinic acid on membrane band 3 in human erythrocytes.

    PubMed

    Fiore, Cristina; Bordin, Luciana; Pellati, Donatella; Armanini, Decio; Clari, Giulio

    2008-11-01

    Glycyrrhetinic acid (GA) is a hydrolytic product of the triterpene glycoside of glycyrrhizic acid, one of the main constituents of licorice root, which has long been studied, due to its several biological and endocrine properties. In this paper, GA was tested on human erythrocytes, and GA-induced alterations were compared with those caused by diamide, a mild oxidant inducing well-characterized cell/membrane alterations, and n-ethylmaleimide (NEM), as alkylating agent. In order to verify the biochemical steps underlying the action of GA, band 3 Tyr-phosphorylation level, enzyme recruitment and band 3 clustering in cells pre-incubated with GA before diamide treatment were all examined. Results show that GA, in a dose-dependent manner, prevents both diamide and NEM-induced band 3 Tyr-phosphorylation, but not GSH decrease caused by both compounds. In addition, diamide-induced band 3 clustering and IgG binding to altered cells were also completely reversed by GA pre-treatment. Also, when membrane sensitivity toward proteolytic digestion was tested, GA-treated cells showed high resistance to proteolysis. In conclusion, in human erythrocytes, GA is proposed to strengthen membrane integrity against both oxidative and proteolytic damage. PMID:18778682

  17. Inhibitory Effects of Glycyrrhetinic Acid on DNA Polymerase and Inflammatory Activities

    PubMed Central

    Ishida, Tsukasa; Mizushina, Yoshiyuki; Yagi, Saori; Irino, Yasuhiro; Nishiumi, Shin; Miki, Ikuya; Kondo, Yasuyuki; Mizuno, Shigeto; Yoshida, Hiromi; Azuma, Takeshi; Yoshida, Masaru

    2012-01-01

    We investigated the inhibitory effect of three glycyrrhizin derivatives, such as Glycyrrhizin (compound 1), dipotassium glycyrrhizate (compound 2) and glycyrrhetinic acid (compound 3), on the activity of mammalian pols. Among these derivatives, compound 3 was the strongest inhibitor of mammalian pols α, β, κ, and λ, which belong to the B, A, Y, and X families of pols, respectively, whereas compounds 1 and 2 showed moderate inhibition. Among the these derivatives tested, compound 3 displayed strongest suppression of the production of tumor necrosis factor-α (TNF-α) induced by lipopolysaccharide (LPS) in a cell-culture system using mouse macrophages RAW264.7 and peritoneal macrophages derived from mice. Moreover, compound 3 was found to inhibit the action of nuclear factor-κB (NF-κB) in engineered human embryonic kidney (HEK) 293 cells. In addition, compound 3 caused greater reduction of 12-O-tetradecanoylphorbol-13-acetate-(TPA-) induced acute inflammation in mouse ear than compounds 1 and 2. In conclusion, this study has identified compound 3, which is the aglycone of compounds 1 and 2, as a promising anti-inflammatory candidate based on mammalian pol inhibition. PMID:21785649

  18. Combretastatin A4 disodium phosphate-induced myocardial injury.

    PubMed

    Tochinai, Ryota; Nagata, Yuriko; Ando, Minoru; Hata, Chie; Suzuki, Tomo; Asakawa, Naoyuki; Yoshizawa, Kazuhiko; Uchida, Kazumi; Kado, Shoichi; Kobayashi, Toshihide; Kaneko, Kimiyuki; Kuwahara, Masayoshi

    2016-07-01

    Histopathological and electrocardiographic features of myocardial lesions induced by combretastatin A4 disodium phosphate (CA4DP) were evaluated, and the relation between myocardial lesions and vascular changes and the direct toxic effect of CA4DP on cardiomyocytes were discussed. We induced myocardial lesions by administration of CA4DP to rats and evaluated myocardial damage by histopathologic examination and electrocardiography. We evaluated blood pressure (BP) of CA4DP-treated rats and effects of CA4DP on cellular impedance-based contractility of human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs). The results revealed multifocal myocardial necrosis with a predilection for the interventricular septum and subendocardial regions of the apex of the left ventricular wall, injury of capillaries, morphological change of the ST junction, and QT interval prolongation. The histopathological profile of myocardial lesions suggested that CA4DP induced a lack of myocardial blood flow. CA4DP increased the diastolic BP and showed direct effects on hiPS-CMs. These results suggest that CA4DP induces dysfunction of small arteries and capillaries and has direct toxicity in cardiomyocytes. Therefore, it is thought that CA4DP induced capillary and myocardial injury due to collapse of the microcirculation in the myocardium. Moreover, the direct toxic effect of CA4DP on cardiomyocytes induced myocardial lesions in a coordinated manner. PMID:27559241

  19. Safety of gadoxetate disodium: results from six clinical phase IV studies in 8194 patients

    PubMed Central

    Kim, So Yeon; Sakaguchi, Toshiaki; Dohanish, Susan; Breuer, Josy

    2015-01-01

    Background Safety data on routine clinical use of gadoxetate disodium for liver magnetic resonance imaging (MRI) is not reported yet. Purpose To assess the safety profile of gadoxetate disodium for liver MRI in the routine clinical setting. Material and Methods Six multicenter studies were performed in Europe, USA, Australia, and Asia to evaluate the safety and efficacy of gadoxetate disodium (Primovist®/Eovist®) enhanced liver MRI. Patients received a single intravenous bolus injection of the standard approved dose of 0.025 mmol/kg body weight (0.1 mL/kg). The number of patients, the characteristics of adverse events, related adverse events, and serious adverse events were analyzed. Results A total of 8194 patients were included in the database. A total of 141 patients (1.7%) reported 230 AEs of which 129 were considered being related to the use of gadoxetate disodium by the investigators. None of the AEs in the pediatric population (n = 52) were related. The most frequent AEs independent of relationship to the drug included dyspnea (25/0.31%), nausea (22/0.27%), liver disorders (13/0.16%), and renal disorders (9/0.11%). Nine related SAEs were recorded. No patient died during the studies. Conclusion Gadoxetate disodium for liver MRI is safe and well tolerated in the routine clinical setting. PMID:26048848

  20. Preparation and Antibacterial Activity Evaluation of 18-β-glycyrrhetinic Acid Loaded PLGA Nanoparticles

    PubMed Central

    Darvishi, Behrad; Manoochehri, Saeed; Kamalinia, Golnaz; Samadi, Nasrin; Amini, Mohsen; Mostafavi, Seyyed Hossein; Maghazei, Shahab; Atyabi, Fatemeh; Dinarvand, Rassoul

    2015-01-01

    The aim of the present study was to formulate poly (lactide-co-glycolide) (PLGA) nanoparticles loaded with 18-β-glycyrrhetinic acid (GLA) with appropriate physicochemical properties and antimicrobial activity. GLA loaded PLGA nanoparticles were prepared with different drug to polymer ratios, acetone contents and sonication times and the antibacterial activity of the developed nanoparticles was examined against different gram-negative and gram-positive bacteria. The antibacterial effect was studied using serial dilution technique to determine the minimum inhibitory concentration of nanoparticles. Results demonstrated that physicochemical properties of nanoparticles were affected by the above mentioned parameters where nanoscale size particles ranging from 175 to 212 nm were achieved. The highest encapsulation efficiency (53.2 ± 2.4%) was obtained when the ratio of drug to polymer was 1:4. Zeta potential of the developed nanoparticles was fairly negative (-11±1.5). In-vitro release profile of nanoparticles showed two phases: an initial phase of burst release for 10 h followed by a slow release pattern up to the end. The antimicrobial results revealed that the nanoparticles were more effective than pure GLA against P. aeuroginosa, S. aureus and S. epidermidis. This improvement in antibacterial activity of GLA loaded nanoparticles when compared to pure GLA may be related to higher nanoparticles penetration into infected cells and a higher amount of GLA delivery in its site of action. Herein, it was shown that GLA loaded PLGA nanoparticles displayed appropriate physicochemical properties as well as an improved antimicrobial effect. PMID:25901144

  1. Glycyrrhetinic acid as inhibitor or amplifier of permeability transition in rat heart mitochondria.

    PubMed

    Battaglia, Valentina; Brunati, Anna Maria; Fiore, Cristina; Rossi, Carlo Alberto; Salvi, Mauro; Tibaldi, Elena; Palermo, Mario; Armanini, Decio; Toninello, Antonio

    2008-01-01

    Glycyrrhetinic acid (GE), a hydrolysis product of glycyrrhizic acid, one of the main constituents of licorice root, is able, depending on its concentration, to prevent or to induce the mitochondrial permeability transition (MPT) (a phenomenon related to oxidative stress) in rat heart mitochondria (RHM). In RHM, below a threshold concentration of 7.5 microM, GE prevents oxidative stress and MPT induced by supraphysiological Ca2+ concentrations. Above this concentration, GE induces oxidative stress by interacting with a Fe-S centre of Complex I, thus producing ROS, and amplifies the opening of the transition pore, once again induced by Ca2+. GE also inhibits Ca2+ transport in RHM, thereby preventing the oxidative stress induced by the cation. However, the reduced amount of Ca2+ transported in the matrix is sufficient to predispose adenine nucleotide translocase for pore opening. Comparisons between observed results and the effects of GE in rat liver mitochondria (RLM), in which the drug induces only MPT without exhibiting any protective effect, confirm that it interacts in a different way with RHM, suggesting tissue specificity for its action. The concentration dependence of the opposite effects of GE, in RHM but not RLM, is most probably due to the existence of a different, more complex, pathway by means of which GE reaches its target. It follows that high GE concentrations are necessary to stimulate the oxidative stress capable of inducing MPT, because of the above effect, which prevents the interaction of low concentrations of GE with the Fe-S centre. The reported results also explain the mechanism of apoptosis induction by GE in cardiomyocytes. PMID:17980701

  2. Laminaria japonica increases plasma exposure of glycyrrhetinic acid following oral administration of Liquorice extract in rats.

    PubMed

    Zhao, Wei-Man; Jiang, Shu-Wen; Chen, Yang; Zhong, Ze-Yu; Wang, Zhong-Jian; Zhang, Mian; Li, Ying; Xu, Ping; Liu, Li; Liu, Xiao-Dong

    2015-07-01

    The present study was designed to investigate the effects of Laminaria japonica (Laminaria) on pharmacokinetics of glycyrrhetinic acid (GA) following oral administration of Liquorice extract in rats. Following oral administrations of single-dose and multi-dose Liquorice extract and Liquorice-Laminaria extract, respectively, plasma samples were obtained at various times and the concentrations of GA, liquiritigenin, and isoliquiritigenin were measured by LC-MS. The effects of Laminaria extract on pharmacokinetics of GA were also investigated, following single-dose and multidose of glycyrrhizic acid (GL). The effects of Laminaria extract on intestinal absorption of GA and GL were studied using the in situ single-pass intestinal perfusion model. The metabolism of GL to GA in the contents of small and large intestines was also studied. The results showed Liquorice-Laminaria extract markedly increased the plasma concentration of GA, accompanied by a shorter Tmax. Similar alteration was observed following multidose administration. However, pharmacokinetics of neither liquiritigenin nor isoliquiritigenin was affected by Laminaria. Similarly, Laminaria markedly increased concentration and decreased Tmax of GA following oral GL were observed. The data from the intestinal perfusion model showed that Laminaria markedly increased GL absorption in duodenum and jejunum, but did not affect the intestinal absorption of GA. It was found that Laminaria enhanced the metabolism of GL to GA in large intestine. In conclusion, Laminaria increased plasma exposures of GA following oral administration of liquorice or GL, which partly resulted from increased intestinal absorption of GL and metabolism of GL to GA in large intestine.

  3. Effect of glycyrrhetinic acid on lipid raft model at the air/water interface.

    PubMed

    Sakamoto, Seiichi; Uto, Takuhiro; Shoyama, Yukihiro

    2015-02-01

    To investigate an interfacial behavior of the aglycon of glycyrrhizin (GC), glycyrrhetinic acid (GA), with a lipid raft model consisting of equimolar ternary mixtures of N-palmitoyl sphingomyelin (PSM), dioleoylphosphatidylcholine (DOPC), and cholesterol (CHOL), Langmuir monolayer techniques were systematically conducted. Surface pressure (π)-molecular area (A) and surface potential (ΔV)-A isotherms showed that the adsorbed GA at the air/water interface was desorbed into the bulk upon compression of the lipid monolayer. In situ morphological analysis by Brewster angle microscopy and fluorescence microscopy revealed that the raft domains became smaller as the concentrations of GA in the subphase (CGA) increased, suggesting that GA promotes the formation of fluid networks related to various cellular processes via lipid rafts. In addition, ex situ morphological analysis by atomic force microscopy revealed that GA interacts with lipid raft by lying down at the surface. Interestingly, the distinctive striped regions were formed at CGA=5.0 μM. This phenomenon was observed to be induced by the interaction of CHOL with adsorbed GA and is involved in the membrane-disrupting activity of saponin and its aglycon. A quantitative comparison of GA with GC (Sakamoto et al., 2013) revealed that GA interacts more strongly with the raft model than GC in the monolayer state. Various biological activities of GA are known to be stronger than those of GC. This fact allows us to hypothesize that differences in the interactions of GA/GC with the model monolayer correlate to their degree of exertion for numerous activities.

  4. Gap-junction disassembly and connexin 43 dephosphorylation induced by 18 beta-glycyrrhetinic acid.

    PubMed

    Guan, X; Wilson, S; Schlender, K K; Ruch, R J

    1996-07-01

    Gap-junction channels connect the interiors of adjacent cells and can be arranged into aggregates or plaques consisting of hundreds to thousands of channel particles. The mechanism of channel aggregation into plaques and whether plaques can disaggregate are not known. Many carcinogenic and tumor-promoting chemicals have been identified that inhibit cell-cell gap-junctional coupling. Here, we provide morphological evidence that 18 beta-glycyrrhetinic acid (18 beta-GA), a saponin isolated from licorice root that is an inhibitor of gap-junctional communication, caused the disassembly of gap-junction plaques in WB-F344 rat liver epithelial cells. This effect was dose (5-40 microM) and time dependent (1-4 h treatment). Gap-junction channels in WB-F344 cells are comprised of connexin 43 (Cx43), and the protein is phosphorylated to a species known as Cx43-P2 coincident with the assembly of channels into plaques. Consistent with this, the disassembly of plaques induced by 18 beta-GA was correlated with decreases in Cx43-P2 levels and increases in nonphosphorylated Cx43. Biochemical evidence indicated that these changes in the P2 and NP forms of Cx43 represented 18 beta-GA-induced dephosphorylation of Cx43-P2 and not its degradation or the inhibition of Cx43-NP phosphorylation. Okadaic acid and calyculin A, which are inhibitors of type 1 and type 2A protein phosphatases, prevented the dephosphorylation of Cx43, suggesting that one or both of these phosphatases were involved in Cx43 dephosphorylation. These data indicate that 18 beta-GA causes type 1 or type 2A protein phosphatase-mediated Cx43 dephosphorylation coincident with the disassembly of gap-junction plaques.

  5. Simple spectrophotometric method for estimation of disodium edetate in topical gel formulations

    PubMed Central

    Kamboj, Sunil; Sharma, Deepak; Nair, Anroop B.; Kamboj, Suman; Sharma, Rakesh Kumar; Ali, Javed; Pramod, K; Ansari, S. H.

    2011-01-01

    A simple, sensitive, cost-effective and reproducible UV-spectrophotometric method has been developed and validated for the estimation of disodium edetate in topical gel formulations. Solution of disodium edetate reacts with ferric chloride to form complex in 0.1 N HCl giving λmax at 270 nm. Beer's law was obeyed in the concentration range of 5–50 μg/mL (r2= 0.9997). The limit of detection and limit of quantitation were found to be 1.190 and 3.608 μg/mL, respectively. The results show that the procedure is accurate, precise, and reproducible (relative standard deviation < 1%), while being simple and less time consuming. The study concluded that the UV-spectrophotometric method could be used for the quantification of disodium edetate in pure form as well as in pharmaceutical formulations. PMID:23781446

  6. 18{beta}-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

    SciTech Connect

    Moon, Myung-Hee; Jeong, Jae-Kyo; Lee, You-Jin; Seol, Jae-Won; Ahn, Dong-Choon; Kim, In-Shik; Park, Sang-Youel

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer 18{beta}-GA inhibits adipogenic differentiation in 3T3-L1 preadipocytes and stimulates lipolysis in differentiated adipocytes. Black-Right-Pointing-Pointer Anti-adipogenic effect of 18{beta}-GA is caused by down-regulation of PPAR{gamma} and inactivation of Akt signalling. Black-Right-Pointing-Pointer Lipolytic effect of 18{beta}-GA is mediated by up-regulation of HSL, ATGL and perilipin and activation of HSL. -- Abstract: 18{beta}-Glycyrrhetinic acid (18{beta}-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18{beta}-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18{beta}-GA dose-dependently (1-40 {mu}M) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 {mu}M of 18{beta}-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor {gamma}, CCAAT/enhancer-binding protein {alpha} and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18{beta}-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18{beta

  7. A subchronic oral toxicity study on pyrroloquinoline quinone (PQQ) disodium salt in rats.

    PubMed

    Liang, Chunlai; Zhang, Xin; Wang, Wei; Song, Yan; Jia, Xudong

    2015-01-01

    A subchronic oral toxicity study on pyrroloquinoline quinone (PQQ) disodium salt was performed in rats. Sprague-Dawley rats were randomly divided into four groups (10 rats/sex/group) and administered with PQQ disodium salt at doses of 0 (control), 100, 200 and 400 mg/kg bw/day by gavage for 13 weeks. Daily clinical observations and weekly measurement of body weights and food consumption were conducted. Blood samples were obtained on day 46 and day 91 for measurement of hematology and serum biochemical parameters. Animals were euthanized for necropsy, selected organs were weighted and recorded. Histological examination was performed on all tissues from animals in the control and PQQ disodium salt treatment groups. No mortality or toxicologically significant changes in clinical signs, body weight, food consumption, necropsy findings or organ weights was observed. Differences between treated and control groups in some hematological and serum biochemical examinations and histopathological examination were not considered treatment-related. The no-observed-adverse-effect-level (NOAEL) of PQQ disodium salt in rats was considered to be 400 mg/kg bw/day for both sexes, the highest dose tested.

  8. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  9. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  10. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  11. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... milligrams of dibasic sodium phosphate, 5 milligrams of sodium chloride, 0.1 milligram of disodium EDTA, 0.5 milligram of polysorbate 80, 9 milligrams of benzyl alcohol, 5 milligrams of sodium carboxymethylcellulose, 1.8 milligrams of methylparaben, 0.2 milligram of propylparaben, hydrochloric acid and/or...

  12. 18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents.

    PubMed

    Huang, Li-Rong; Hao, Xiao-Jiang; Li, Qi-Ji; Wang, Dao-Ping; Zhang, Jian-Xin; Luo, Heng; Yang, Xiao-Sheng

    2016-04-22

    The oleanane-type triterpene 18β-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

  13. Self-assembly modes of glycyrrhetinic acid esters in view of the crystal packing of related triterpene molecules.

    PubMed

    Langer, Dominik; Wicher, Barbara; Szczołko, Wojciech; Gdaniec, Maria; Tykarska, Ewa

    2016-08-01

    The crystal structures of three ester derivatives of glycyrrhetinic acid (GE) are reported. X-ray crystallography revealed that despite differences in the size of the ester substituents (ethyl, isopropyl and 2-morpholinoethyl) the scheme of molecular self-assembly is similar in all three cases but differs significantly from that observed in other known GE esters. According to our analysis, the two basic patterns of self-assembly of GE esters observed in their unsolvated crystals correspond to two distinct orientations of the ester groups relative to the triterpene backbone. Moreover, comparison of the self-assembly modes of GE esters in their unsolvated forms with the supramolecular organization of GE and carbenoxolone in their solvated crystals revealed that ester substituents replace solvent molecules hydrogen bonded to the COOH group at the triterpene skeleton, resulting in similar packing arrangements of these compounds. PMID:27484379

  14. Alginate immobilization of Escherichia coli MTCC 1652 whole cells for bioconversion of glycyrrhizinic acid and into 18-beta glycyrrhetinic acid.

    PubMed

    Ahmad, M; Panda, B P

    2013-12-15

    Microbial biotransformation of Glycyrrhizinic acid (GL) into 18-beta Glycyrrhetinic Acid (GA) was achieved using Escherichia coli MTCC 1652 whole cell. The E. coli whole cell was immobilized by entrapment method within calcium alginate beads using cell suspension of equal volume with sodium alginate 8%. The pH of solution, reaction volume and % of GL were optimized during the immobilization procedure and optimum pH 6.5, reaction volume of 4 mL and at 3% GL concentration for 12 h of incubation time showed highest concentration of GA (72.649 microg mL(-1)) with 76% bioconversion of GL to GA. Under optimized condition the immobilized cell produces 58.663 microg per mL of GA in licorice root extract containing 95.118 microg of GL per mL of the extract with 61% conversion at 12 h.

  15. Effect of aldosterone and glycyrrhetinic acid on the protein expression of PAI-1 and p22(phox) in human mononuclear leukocytes.

    PubMed

    Calò, Lorenzo A; Zaghetto, Francesca; Pagnin, Elisa; Davis, Paul A; De Mozzi, Paola; Sartorato, Paola; Martire, Giuseppe; Fiore, Cristina; Armanini, Decio

    2004-04-01

    Aldosterone excess can produce heart and kidney fibrosis, which seem to be related to a direct effect of aldosterone at the level of specific receptors. We report a direct, mineralocorticoid-mediated effect on the protein expression of two markers of oxidative stress after incubation of mononuclear leukocytes with 1 x 10(-8) M aldosterone (p22(phox)/beta-actin = 1.38 +/- 0.05 and PAI-1/beta-actin = 1.80 +/- 0.05). The same effect was also found with 3 x 10(-5) M glycyrrhetinic acid, the principal constituent of licorice root (p22(phox)/beta-actin = 1.37 +/- 0.97 and PAI-1/beta-actin = 1.80 +/- 0.04). The effect of both aldosterone and glycyrrhetinic acid is blocked by incubation with added 1 x 10(-6) M of receptor-antagonist canrenone. Canrenone alone did not show any effect. PAI-1 related protein was also found using 4 x 10(-9) M aldosterone. Incubations with 1 x 10(-9) M for 3 hours as well as 1 x 10(-8) M aldosterone for 5, 10, and 20 minutes were ineffective for both proteins. These data support the previous finding of an involvement of mononuclear leukocytes in the pathogenesis of the oxidative stress induced by hyperaldosteronism. In addition, the results confirm our previous data on a direct effect of glycyrrhetinic acid at the level of mineralocorticoid receptors. PMID:15070972

  16. Edetate Disodium-Based Treatment for Secondary Prevention in Post-Myocardial Infarction Patients.

    PubMed

    Lamas, Gervasio A; Issa, Omar M

    2016-02-01

    An abundance of data, known for decades, is available linking metals, such as lead and cadmium, with cardiovascular disease. However, the idea that these toxic metals could be a modifiable risk factor for atherosclerosis did not become apparent clinically until the completion of the Trial to Assess Chelation Therapy in 2012. This pivotal study was the first double-blind, randomized, controlled trial of its kind to demonstrate a clear improvement in cardiovascular outcomes with edetate disodium therapy in a secondary prevention, post-myocardial infarction population. This effect size was most striking in diabetic patients, where the efficacy of edetate disodium was comparable, if not superior, to that of current guideline-based therapies. Given the economic burden of diabetes and cardiovascular disease, the potential impact of this therapy could be enormous if the results of this study are replicated.

  17. Surface-enhanced raman scattering from ethylenediaminetetraacetic-disodium salt and nitrate ions on silver electrodes

    NASA Astrophysics Data System (ADS)

    Wetzel, H.; Pettinger, B.; Wenning, U.

    1980-10-01

    Surface-enhanced Raman scattering (SERS) from ethylenediaminetetraacetic-disodium salt adsorbed on silver electrodes has been obtained for the 913, 935 and 1408 cm -1 modes. Addition of this salt to NaNO 3 solutions leads to an enhancement of the NO -3 band at 1050 cm -1. Oxidation/reduction cycles leading to surface roughening and a photochemical reaction caused by the exciting light are prerequisites for these enhancements. The SER signal can irreversibly be quenched by cathodic polarisation.

  18. Human disodium octaborate tetrahydrate exposure following carpet flea treatment is not associated with significant dermal absorption.

    PubMed

    Krieger, R I; Dinoff, T M; Peterson, J

    1996-01-01

    Disodium octaborate tetrahydrate is used for indoor flea control on carpets and furniture. Disodium octaborate tetrahydrate was applied to a 100% nylon carpet as a solution using a powered rug brush at a rate of approximately 200 micrograms/cm2 carpet. Two randomly chosen groups of volunteers (18 females, 4 males) wore either bathing suits which provided 75% or more skin exposure or whole-body, cotton dosimeters consisting of socks, union suits, and gloves. The volunteers performed a 20-minute set of Jazzercise routines. The availability of boron was demonstrated by covering portions of the carpet with a cotton dosimeter and rolling it with a weighted roller. Additionally, disodium octaborate tetrahydrate was transferred to the whole-body dosimeter. Volunteers also collected 24-hour urine specimens prior to and following the exercise period. The specimens were analyzed for total boron by inductively coupled plasma emission spectroscopy. No evidence of contact transfer and dermal absorption was obtained. The mean daily boron levels (mg/g creatinine) were 1.17, 1.33, and 1.31 for the group with exposed skin and 1.26, 1.12, and 1.26 for those who wore dosimeters which prevented contact. Daily urine boron levels were not significantly different when compared using a two sample t-test assuming equal variances (P > 0.05). Direct dermal contact with disodium octaborate tetrahydrate-treated carpet at a nominal rate of 200 micrograms/cm2 did not produce any adverse effects or change urinary boron clearance. PMID:8889949

  19. The pharmacokinetics of subcutaneously injected Bimosiamose disodium in healthy male volunteers.

    PubMed

    Meyer, Michael; Beyer, Diana; Vollhardt, Karin; Woischwill, Christiane; Jilma, Bernd; Wolff, Gerhard

    2007-12-01

    Bimosiamose is a novel synthetic pan-selectin antagonist developed for the treatment of acute and chronic inflammatory disorders. Therefore the pharmacokinetics of Bimosiamose disodium were studied in healthy male volunteers after single and multiple subcutaneous injections. A randomized, double-blind, placebo-controlled dose escalation trial was carried out. The subjects received subcutaneous injections of placebo or 100, 200 or 300 mg Bimosiamose disodium into the abdomen. Plasma and urine concentrations of Bimosiamose were determined. The maximum plasma concentration was 2.17+/-0.70 microg/ml and the AUC(0-infinity) 11.1+/-2.9 h microg/ml after the highest dose on day 1 (mean+/-SD). For the apparent clearance CL/f 28.7+/-7.3 l/h and the terminal half life t(1/2) 3.7+/-0.6 h were calculated. The mean residence time MRT(infinity) of 5.5 to 6.3 h for s.c. injection exceeded that after i.v. infusion due to an extended absorption time. For multiple dosing, constant pre-dose concentrations of about 20 ng/ml may be reached after two subsequent doses of 200 or 300 mg Bimosiamose disodium once daily. Almost 15% of the administered drug was excreted unchanged in urine. Moreover, Bimosiamose was well tolerated. PMID:17876866

  20. Effect of edetate disodium and reduced glutathione on absorption of acetazolamide from GI tract of rats.

    PubMed

    Schoenwald, R D; Ward, R L

    1976-05-01

    The absorption of acetazolamide suspensions from in situ rat gastric and intestinal loop segments was studied. In 1 hr, 66.2 and 64.3% remained unabsorbed from the rat stomach and intestine, respectively. Although 1% (w/v) reduced glutathione and 1% (w/v) (24 mM) edetate disodium had no effect on gastric absorption, drug absorption from the rat intestine (1 hr) was increased 1.5 and 2 times, respectively. It was hypothesized that the relatively poor intestinal absorption was due primarily to the formation of a pH-dependent (pH 4.5-10), nonabsorbable complex between acetazolamide and carbonic anhydrase present in the gut and that reduced glutathione acted as an inhibitor to promote intestinal absorption. Equilibrium dialysis studies showed that reduced glutathion could reduce the fraction of drug bound to human carbonic anhydrase B by one-half when present in a molar ratio 10 times that of acetazolamide; edetate disodium had no effect on the in vitro binding. It was, therefore, assumed that edetate disodium promoted an increase in intestinal absorption by altering the permeability of intestinal epithelium. Based upon present experimentation, however, the alteration of intestinal epithelium by reduced glutathione cannot be ruled out. PMID:6773

  1. A novel glucuronosyltransferase has an unprecedented ability to catalyse continuous two-step glucuronosylation of glycyrrhetinic acid to yield glycyrrhizin.

    PubMed

    Xu, Guojie; Cai, Wei; Gao, Wei; Liu, Chunsheng

    2016-10-01

    Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world-wide. However, the key UDP-dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown. To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay. Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two-step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site-directed mutagenesis revealed that Gln-352 may be important for the initial step of glucuronosylation, and His-22, Trp-370, Glu-375 and Gln-392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two-step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products. Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin. PMID:27252088

  2. One-step Conjugation of Glycyrrhetinic Acid to Cationic Polymers for High-performance Gene Delivery to Cultured Liver Cell

    PubMed Central

    Cong, Yue; Shi, Bingyang; Lu, Yiqing; Wen, Shihui; Chung, Roger; Jin, Dayong

    2016-01-01

    Gene therapies represent a promising therapeutic route for liver cancers, but major challenges remain in the design of safe and efficient gene-targeting delivery systems. For example, cationic polymers show good transfection efficiency as gene carriers, but are hindered by cytotoxicity and non-specific targeting. Here we report a versatile method of one-step conjugation of glycyrrhetinic acid (GA) to reduce cytotoxicity and improve the cultured liver cell -targeting capability of cationic polymers. We have explored a series of cationic polymer derivatives by coupling different ratios of GA to polypropylenimine (PPI) dendrimer. These new gene carriers (GA-PPI dendrimer) were systematically characterized by UV-vis,1H NMR titration, electron microscopy, zeta potential, dynamic light-scattering, gel electrophoresis, confocal microscopy and flow cytometry. We demonstrate that GA-PPI dendrimers can efficiently load and protect pDNA, via formation of nanostructured GA-PPI/pDNA polyplexes. With optimal GA substitution degree (6.31%), GA-PPI dendrimers deliver higher liver cell transfection efficiency (43.5% vs 22.3%) and lower cytotoxicity (94.3% vs 62.5%, cell viability) than the commercial bench-mark DNA carrier bPEI (25kDa) with cultured liver model cells (HepG2). There results suggest that our new GA-PPI dendrimer are a promising candidate gene carrier for targeted liver cancer therapy. PMID:26902258

  3. Glycyrrhetinic Acid and Its Derivatives: Anti-Cancer and Cancer Chemopreventive Properties, Mechanisms of Action and Structure- Cytotoxic Activity Relationship.

    PubMed

    Roohbakhsh, Ali; Iranshahy, Milad; Iranshahi, Mehrdad

    2016-01-01

    The anti-cancer properties of liquorice have been attributed, at least in part, to glycyrrhizin (GL). However, GL is not directly absorbed through the gastrointestinal tract. It is hydrolyzed to 18-β-glycyrrhetinic acid (GA), the pharmacologically active metabolite, by human intestinal microflora. GA exhibits remarkable cytotoxic and anti-tumor properties. The pro-apoptotic targets and mechanisms of action of GA have been extensively studied over the past decade. In addition, GA is an inexpensive and available triterpene with functional groups (COOH and OH) in its structure, which make it an attractive lead compound for medicinal chemists to prepare a large number of analogues. To date, more than 400 cytotoxic derivatives have been prepared on the basis of GA scaffold, including 128 cytotoxic derivatives with IC50 values less than 30 µM. Researchers have also succeeded in synthesizing very potent cytotoxic derivatives with IC50s ≤ 1 µM. Studies have shown that the introduction of a double bound at the C1-C2 position combined with an electronegative functional group, such as CN, CF3 or iodine at C2 position, and the oxidation of the hydroxyl group of C3 to the carbonyl group, significantly increased cytotoxicity. This review describes the cytotoxic and anti-tumor properties of GA and its derivatives, targets and mechanisms of action and provides insight into the structure-activity relationship of GA derivatives.

  4. Induction of Apoptosis and Nonsteroidal Antiinflammatory Drug-Activated Gene 1 in Pancreatic Cancer Cells By A Glycyrrhetinic Acid Derivative

    PubMed Central

    Jutooru, Indira; Chadalapaka, Gayathri; Chintharlapalli, Sudhakar; Papineni, Sabitha; Safe, Stephen

    2009-01-01

    Methyl 2-cyano-3,11-dioxo-18β-olean-1,12-dien-30-oate (CDODA-Me) is a synthetic triterpenoid derived from glycyrrhetinic acid, a bioactive phytochemical in licorice, CDODA-Me inhibits growth of Panc1 and Panc28 pancreatic cancer cell lines and activates peroxisome proliferator-activated receptor γ (PPARγ)-dependent transactivation in these cells. CDODA-Me also induced p21 and p27 protein expression and downregulates cyclin D1; however, these responses were receptor-independent. CDODA-Me induced apoptosis in Panc1 and Panc28 cells, and this was accompanied by receptor-independent induction of the proapoptotic proteins early growth response-1 (Egr-1), nonsteroidal anti-inflammatory drug-activated gene-1 (NAG-1), and activating transcription factor-3 (ATF3). Induction of NAG-1 and Egr-1 by CDODA-Me was dependent on activation of phosphatidylinositol-3-kinase (PI3-K) and/or p42 and p38 mitogen-activated protein kinase (MAPK) pathways but there were differences between Panc28 and Panc1 cells. Induction of NAG-1 in Panc28 cells was p38-MAPK- and PI3-K-dependent but Egr-1-independent, whereas induction in Panc1 cells was associated with activation of p38-MAPK, PI3-K and p42-MAPK and was only partially Egr-1-dependent. This is the first report of the induction of the proapoptotic protein NAG-1 in pancreatic cancer cells. PMID:19125423

  5. The Protective Effects of 18β-Glycyrrhetinic Acid on Helicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils.

    PubMed

    Cao, Donghui; Jiang, Jing; You, Lili; Jia, Zhifang; Tsukamoto, Tetsuya; Cai, Hongke; Wang, Shidong; Hou, Zhen; Suo, Yue-er; Cao, Xueyuan

    2016-01-01

    18β-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower (2.14 ± 0.08 versus 3.17 ± 0.23, P < 0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P < 0.05), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased (P < 0.05) compared with the H. pylori-infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug.

  6. A novel glucuronosyltransferase has an unprecedented ability to catalyse continuous two-step glucuronosylation of glycyrrhetinic acid to yield glycyrrhizin.

    PubMed

    Xu, Guojie; Cai, Wei; Gao, Wei; Liu, Chunsheng

    2016-10-01

    Glycyrrhizin is an important bioactive compound that is used clinically to treat chronic hepatitis and is also used as a sweetener world-wide. However, the key UDP-dependent glucuronosyltransferases (UGATs) involved in the biosynthesis of glycyrrhizin remain unknown. To discover unknown UGATs, we fully annotated potential UGATs from Glycyrrhiza uralensis using deep transcriptome sequencing. The catalytic functions of candidate UGATs were determined by an in vitro enzyme assay. Systematically screening 434 potential UGATs, we unexpectedly found one unique GuUGAT that was able to catalyse the glucuronosylation of glycyrrhetinic acid to directly yield glycyrrhizin via continuous two-step glucuronosylation. Expression analysis further confirmed the key role of GuUGAT in the biosynthesis of glycyrrhizin. Site-directed mutagenesis revealed that Gln-352 may be important for the initial step of glucuronosylation, and His-22, Trp-370, Glu-375 and Gln-392 may be important residues for the second step of glucuronosylation. Notably, the ability of GuUGAT to catalyse a continuous two-step glucuronosylation reaction was determined to be unprecedented among known glycosyltransferases of bioactive plant natural products. Our findings increase the understanding of traditional glycosyltransferases and pave the way for the complete biosynthesis of glycyrrhizin.

  7. Enhanced Cellular Cytotoxicity and Antibacterial Activity of 18-β-Glycyrrhetinic Acid by Albumin-conjugated PLGA Nanoparticles.

    PubMed

    Darvishi, B; Manoochehri, S; Esfandyari-Manesh, M; Samadi, N; Amini, M; Atyabi, F; Dinarvand, R

    2015-12-01

    The aim of the present work was to encapsulate 18-β-Glycyrrhetinic acid (GLA) in albumin conjugated poly(lactide-co-glycolide) (PLGA) nanoparticles by a modified nanoprecipitation method. Nanoparticles (NPs) were prepared by different drug to polymer ratios, human serum albumin (HSA) content, dithiothreitol (as producer of free thiol groups) content, and acetone (as non-solvent in nanoprecipitation). NPs with a size ranging from 126 to 174 nm were achieved. The highest entrapment efficiency (89.4±4.2%) was achieved when the ratio of drug to polymer was 1:4. The zeta potential of NPs was fairly negative (-8 to -12). Fourier transform infrared spectroscopy and differential scanning calorimetry proved the conjugation of HSA to PLGA NPs. In vitro release profile of NPs showed 2 phases: an initial burst for 4 h (34-49%) followed by a slow release pattern up to the end. The antibacterial effects of NPs against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa were studied by microdilution method. The GLA-loaded NPs showed more antibacterial effect than pure GLA (2-4 times). The anticancer MTT test revealed that GLA-loaded NPs were approximately 9 times more effective than pure GLA in Hep G2 cells. PMID:25607747

  8. 18β-glycyrrhetinic acid suppresses experimental autoimmune encephalomyelitis through inhibition of microglia activation and promotion of remyelination.

    PubMed

    Zhou, Jieru; Cai, Wei; Jin, Min; Xu, Jingwei; Wang, Yanan; Xiao, Yichuan; Hao, Li; Wang, Bei; Zhang, Yanyun; Han, Jie; Huang, Rui

    2015-01-01

    Microglia are intrinsic immune cells in the central nervous system (CNS). The under controlled microglia activation plays important roles in inflammatory demyelination diseases, such as multiple sclerosis (MS). However, the means to modulate microglia activation as a therapeutic modality and the underlying mechanisms remain elusive. Here we show that administration of 18β-glycyrrhetinic acid (GRA), by using both preventive and therapeutic treatment protocols, significantly suppresses disease severity of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice. The treatment effect of GRA on EAE is attributed to its regulatory effect on microglia. GRA-modulated microglia significantly decreased pro-inflammatory profile in the CNS through suppression of MAPK signal pathway. The ameliorated CNS pro-inflammatory profile prevented the recruitment of encephalitogenic T cells into the CNS, which alleviated inflammation-induced demyelination. In addition, GRA treatment promoted remyelination in the CNS of EAE mice. The induced remyelination can be mediated by the overcome of inflammation-induced blockade of brain-derived neurotrophic factor expression in microglia, as well as enhancing oligodendrocyte precursor cell proliferation. Collectively, our results demonstrate that GRA-modulated microglia suppresses EAE through inhibiting microglia activation-mediated CNS inflammation, and promoting neuroprotective effect of microglia, which represents a potential therapeutic strategy for MS and maybe other neuroinflammatory diseases associated with microglia activation.

  9. Evaluation of the Oral Bioavailability of Low Molecular Weight Heparin Formulated With Glycyrrhetinic Acid as Permeation Enhancer.

    PubMed

    Motlekar, Nusrat A; Srivenugopal, Kalkunte S; Wachtel, Mitchell S; Youan, Bi-Botti C

    2006-02-01

    Low molecular weight heparin (LMWH) is the agent of choice for anticoagulant therapy and prophylaxis of thrombosis and coronary syndromes. However, its therapeutic use is limited due to poor oral bioavailability. The aim of this study was to investigate the oral delivery of LMWH, ardeparin formulated with 18-beta glycyrrhetinic acid (GA), as an alternative to currently used subcutaneous (sc) delivery. Drug transport through Caco-2 cell monolayers was monitored in the presence and absence of GA by scintillation counting and transepithelial electrical resistance. Regional permeability studies using rat intestine were performed using a modified Ussing chamber. Cell viability in the presence of various concentrations of enhancer was determined by MTT assay. The absorption of ardeparin after oral administration in rats was measured by an anti-factor Xa assay. Furthermore, the eventual mucosal epithelial damage was histologically evaluated. Higher ardeparin permeability (~7-fold) compared to control was observed in the presence of 0.02 % GA. Regional permeability studies indicated predominant absorption in the duodenal segment. Cell viability studies showed no significant cytotoxicity below 0.01 % GA. Ardeparin oral bioavailability was significantly increased (F(relative)/(S.C). = 13.3%) without causing any damage to the intestinal tissues. GA enhanced the oral absorption of ardeparin both in vitro and in vivo. The oral formulation of ardeparin with GA could be absorbed in the intestine. These results suggest that GA may be used as an absorption enhancer for the oral delivery of LMWH. PMID:17710191

  10. The Protective Effects of 18β-Glycyrrhetinic Acid on Helicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils

    PubMed Central

    Cao, Donghui; Jiang, Jing; You, Lili; Jia, Zhifang; Tsukamoto, Tetsuya; Cai, Hongke; Wang, Shidong; Hou, Zhen; Suo, Yue-er; Cao, Xueyuan

    2016-01-01

    18β-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower (2.14 ± 0.08 versus 3.17 ± 0.23, P < 0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P < 0.05), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased (P < 0.05) compared with the H. pylori-infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug. PMID:27006947

  11. A novel glycyrrhetinic acid-modified oxaliplatin liposome for liver-targeting and in vitro/vivo evaluation.

    PubMed

    Chen, Jingde; Jiang, Hong; Wu, Yin; Li, Yandong; Gao, Yong

    2015-01-01

    In this study, oxaliplatin (OX) liposomes surface-modified with glycyrrhetinic acid (GA) were developed by the film-dispersion method. Their morphology, physical and chemical properties, and in vitro release performance were investigated. The transmission electron microscope (TEM) image showed that most liposomes were spherical particles with similar size and uniform dispersion. Both OX-liposomes and GA-OX-liposomes had an average size of 90 nm. They were negatively charged, with zeta potentials of -20.6 and -21.3 mV, respectively, and the entrapment efficiency values of both were higher than 94%. In vitro data showed that the application of liposomes could prolong the OX release. The relatively high correlation coefficient values obtained from analyzing the amount of drug released versus the square root of time depicted that release followed the Weibull model. No significant changes were observed after the addition of GA to the liposomes. In vivo, the relatively long time to reach the maximum plasma concentration of OX-liposomes suggested a sustained-release profile of liposomes, which was consistent with the results of the in vitro release study. The increased area under the curve and maximum plasma concentration of OX-liposomes and GA-OX-liposomes demonstrated an increased absorption. The drug concentration in tissues indicated that the GA-modified liposomes delivered OX mainly to liver after intravenous administration. In addition, no severe signs, such as appearance of epithelial necrosis or sloughing of epithelial cells, were detected in histology studies.

  12. DGAEE, a newly synthesized derivative of glycyrrhetinic acid, potently attenuates mouse septic shock via its main metabolite DGA in an IL-10-dependent manner.

    PubMed

    Luo, Jinque; Liu, Mei; Wu, Xin; Dou, Yannong; Xia, Yufeng; Dai, Yue; Wei, Zhifeng

    2015-12-01

    Endotoxin can stimulate inflammatory cytokine release from monocytes/macrophages and result in septic shock. Glycyrrhetinic acid (GA), the main bioactive component of licorice, possesses substantial anti-inflammatory activity. Here, we explored effect of 11-deoxy-18α-glycyrrhetinic acid-30-ethyl ester (DGAEE), a newly synthesized derivative of GA, on septic shock. DGAEE and its main metabolite 11-deoxy-18α-glycyrrhetinic acid (DGA) significantly alleviated septic shock as evidenced by improvements of survival rates, lung histopathological changes and wet/dry ratio in lipopolysaccharide (LPS)/D-galactosamine-stimulated mice, and decreased blood pressure in LPS/D-galactosamine-stimulated rats. The two compounds decreased serum levels of NO, TNF-α, IL-6, IL-1β, and increased the level of IL-10 more potently in mice. In LPS-stimulated RAW 264.7 cells, DGA but not DGAEE showed marked regulation of NO, TNF-α, IL-6 and IL-10 levels, suggesting that DGAEE display anti-shock effect by DGA rather than itself. Moreover, the neutralizing antibody against IL-10 markedly prohibited the inhibitory effect of DGA on the production of cytokines from RAW 264.7 cells, and AS101 (an inhibitor of IL-10 biosynthesis) almost completely reversed the anti-shock effect of DGA in mice. In addition, DGA did not affect activation of NF-κB-p65 and p38 MAPK as well as IκBα degradation, but moderately reduced activation of ERK and JNK, and markedly increased phosphorylation of GSK3β in LPS-stimulated RAW 264.7 cells. LY294002 (an inhibitor of GSK3β phosphorylation) and LiCl (an inhibitor of GSK3β activity) diminished and potentiated increase of IL-10 levels by DGA, respectively. In conclusion, DGAEE alleviates septic shock through DGA in an IL-10-dependent manner, and the mechanism is related to inactivation of GSK3β. PMID:26456500

  13. Outcomes in patients with nonerosive reflux disease treated with a proton pump inhibitor and alginic acid ± glycyrrhetinic acid and anthocyanosides

    PubMed Central

    Di Pierro, Francesco; Gatti, Mario; Rapacioli, Giuliana; Ivaldi, Leandro

    2013-01-01

    Background The purpose of this study was to compare the efficacy of alginic acid alone versus alginic acid combined with low doses of pure glycyrrhetinic acid and bilberry anthocyanosides as an addon to conventional proton pump inhibitor therapy in relieving symptoms associated with nonerosive reflux disease. Methods This prospective, randomized, 8-week, open-label trial was conducted at two centers. Sixty-three patients with persistent symptoms of gastroesophageal reflux disease and normal upper gastrointestinal endoscopy were eligible for the study. Patients in group A (n = 31) were treated with pantoprazole and a formula (Mirgeal®) containing alginic acid and low doses of pure glycyrrhetinic acid + standardized Vaccinium myrtillus extract for 4 weeks, then crossed over to the multi-ingredient formula for a further 4 weeks. Patients in group B (n = 32) were treated pantoprazole and alginic acid alone twice daily, then crossed over to alginic acid twice daily for a further 4 weeks. Efficacy was assessed by medical evaluation of a symptom relief score, estimated using a visual analog scale (0–10). Side effects, tolerability, and compliance were also assessed. Results Of the 63 patients enrolled in the study, 58 (29 in group A and 29 in group B) completed the 8-week trial. The baseline characteristics were comparable between the two groups. During the study, significant differences were recorded in symptom scores for both groups. In group A, symptoms of chest pain, heartburn, and abdominal swelling were less serious than in group B. Treatment A was better tolerated, did not induce hypertension, and had fewer side effects than treatment B. No significant differences in compliance were found between the two groups. Conclusion Use of low doses of pure glycyrrhetinic acid + bilberry anthocyanosides, together with alginic acid as addon therapy, substantially improves symptoms in patients with nonerosive reflux disease without increasing side effects or worsening

  14. Effectiveness of disodium cromoglycate in food-dependent, exercise-induced anaphylaxis: a case report.

    PubMed

    Juji, F; Suko, M

    1994-05-01

    An 18-year-old girl experienced anaphylactic reactions three times and frequent urticaria with exercise after meals that included wheat. Allergy evaluation showed a strong prick test reaction to wheat, and RAST score was 2 for wheat. Exercise provoked a decrease of FEV1 of 7.4% and increase of plasma histamine with no symptoms. Exercise after eating wheat provoked an FEV1 decrease of more than 18.7%, further increase of plasma histamine, urticaria and mild dyspnea. Oral administration of disodium cromoglycate before ingestion of bread and exercise challenge caused a maximal FEV1 increase of 6%, no increase of the plasma histamine, and no symptoms.

  15. Chelation in metal intoxication. XVIII. Combined effects of thiamine and calcium disodium versenate on lead toxicity

    SciTech Connect

    Flora, S.J.S.; Singh, S.; Tandon, S.K.

    1986-01-06

    Calcium disodium ethylenediaminetetra-acetate (Ca-Na/sub 2/EDTA; Versenate) was more effective than thiamine (vitamin B/sub 1/) in enhancing the urinary excretion of lead, reducing tissue lead and restoring lead induced biochemical alterations in rats. However, the combination of CaNa/sub 2/EDTA and vitamin B/sub 1/ enhanced the beneficial effect of CaNa/sub 2/EDTA in lead intoxication and was particularly effective in reducing the brain concentration of lead. 18 references, 1 figure, 2 tables.

  16. Structural basis for 18-β-glycyrrhetinic acid as a novel non-GSH analog glyoxalase I inhibitor

    PubMed Central

    Zhang, Hong; Huang, Qiang; Zhai, Jing; Zhao, Yi-ning; Zhang, Li-ping; Chen, Yun-yun; Zhang, Ren-wei; Li, Qing; Hu, Xiao-peng

    2015-01-01

    Aim: Glyoxalase I (GLOI), a glutathione (GSH)-dependent enzyme, is overexpressed in tumor cells and related to multi-drug resistance in chemotherapy, making GLOI inhibitors as potential anti-tumor agents. But the most studied GSH analogs exhibit poor pharmacokinetic properties. The aim of this study was to discover novel non-GSH analog GLOI inhibitors and analyze their binding mechanisms. Methods: Mouse GLOI (mGLOI) was expressed in BL21 (DE3) pLysS after induction with isopropyl-β-D-1-thiogalactopyranoside and purified using AKTA FPLC system. An in vitro mGLOI enzyme assay was used to screen a small pool of compounds containing carboxyl groups. Crystal structure of the mGLOI-inhibitor complex was determined at 2.3 Å resolution. Molecular docking study was performed using Discovery Studio 2.5 software package. Results: A natural compound 18-β-glycyrrhetinic acid (GA) and its derivative carbenoxolone were identified as potent competitive non-GSH analog mGLOI inhibitors with Ki values of 0.29 μmol/L and 0.93 μmol/L, respectively. Four pentacyclic triterpenes (ursolic acid, oleanolic acid, betulic acid and tripterine) showed weak activities (mGLOI inhibition ratio <25% at 10 μmol/L) and other three (maslinic acid, corosolic acid and madecassic acid) were inactive. The crystal structure of the mGLOI-GA complex showed that the carboxyl group of GA mimicked the γ-glutamyl residue of GSH by hydrogen bonding to the glutamyl sites (residues Arg38B, Asn104B and Arg123A) in the GSH binding site of mGLOI. The extensive van der Waals interactions between GA and the surrounding residues also contributed greatly to the binding of GA and mGLOI. Conclusion: This work demonstrates a carboxyl group to be an important functional feature of non-GSH analog GLOI inhibitors. PMID:26279158

  17. Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid

    PubMed Central

    Li, Jingjing; Chen, Tong; Deng, Feng; Wan, Jingyuan; Tang, Yalan; Yuan, Pei; Zhang, Liangke

    2015-01-01

    We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity. PMID:26346750

  18. Phases and structures of sunset yellow and disodium cromoglycate mixtures in water

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Akihiro; Smith, Gregory P.; Yi, Youngwoo; Xu, Charles; Biffi, Silvia; Serra, Francesca; Bellini, Tommaso; Zhu, Chenhui; Clark, Noel A.

    2016-01-01

    We study phases and structures of mixtures of two representative chromonic liquid crystal materials, sunset yellow FCF (SSY) and disodium cromoglycate (DSCG), in water. A variety of combinations of isotropic, nematic (N ), and columnar (also called M ) phases are observed depending on their concentrations, and a phase diagram is made. We find a tendency for DSCG-rich regions to show higher-order phases while SSY-rich regions show lower-order ones. We observe uniform mesophases only when one of the materials is sparse in the N phases. Their miscibility in M phases is so low that essentially complete phase separation occurs. X-ray scattering and spectroscopy studies confirm that SSY and DSCG molecules do not mix when they form chromonic aggregates and neither do their aggregates when they form M phases.

  19. Effective co-delivery of doxorubicin and curcumin using a glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer micelle for combination cancer chemotherapy.

    PubMed

    Yan, Tingsheng; Li, Dalong; Li, Jiwei; Cheng, Feng; Cheng, Jinju; Huang, Yudong; He, Jinmei

    2016-09-01

    A glycyrrhetinic acid-modified chitosan-cystamine-poly(ε-caprolactone) copolymer (PCL-SS-CTS-GA) micelle was developed for the co-delivery of doxorubicin (DOX) and curcumin (CCM) to hepatoma cells. Glycyrrhetinic acid (GA) was used as a targeting unit to ensure specific delivery. Co-encapsulation of DOX and CCM was facilitated by the incorporation of poly(ε-caprolactone) (PCL) groups. The highest drug loading content was 19.8% and 8.9% (w/w) for DOX and CCM, respectively. The PCL-SS-CTS-GA micelle presented a spherical or ellipsoidal geometry with a mean diameter of approximately 110nm. The surface charge of the micelle changed from negative to positive, when the pH value of the solution decreased from 7.4 to 6.8. Meanwhile, it also exhibited a character of redox-responsive drug release and GA/pH-mediated endocytosis in vitro. In simulated body fluid with 10mM glutathione, the release rate in 12h was 80.6% and 67.2% for DOX and CCM, respectively. The cell uptake of micelles was significantly higher at pH 6.8 than pH 7.4. The combined administration of DOX and CCM was facilitated by PCL-SS-CTS-GA micelle. Results showed that there was strong synergic effect between the two drugs. The PCL-SS-CTS-GA micelle might turn into a promising and effective carrier for improved combination chemotherapy. PMID:27281238

  20. Comparative in vitro studies on disodium EDTA effect with and without Proteus mirabilis on the crystallization of carbonate apatite and struvite

    NASA Astrophysics Data System (ADS)

    Prywer, Jolanta; Olszynski, Marcin; Torzewska, Agnieszka; Mielniczek-Brzóska, Ewa

    2014-06-01

    Effect of disodium EDTA (salt of ethylenediamine tetraacetic acid) on the crystallization of struvite and carbonate apatite was studied. To evaluate such an effect we performed an experiment of struvite and carbonate apatite growth from artificial urine. The crystallization process was induced by Proteus mirabilis to mimic the real urinary tract infection, which usually leads to urinary stone formation. The results demonstrate that disodium EDTA exhibits the effect against P. mirabilis retarding the activity of urease - an enzyme produced by these microorganisms. The spectrophotometric results demonstrate that, with and without P. mirabilis, the addition of disodium EDTA increases the induction time and decreases the growth efficiency compared to the baseline (without disodium EDTA). These results are discussed from the standpoint of speciation of complexes formed in the solution of artificial urine in the presence of disodium EDTA. The size of struvite crystals was found to decrease in the presence of disodium EDTA. However, struvite crystals are larger in the presence of bacteria while the crystal morphology and habit remain unchanged.

  1. Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats.

    PubMed

    Nakano, Masahiko; Takahashi, Hisaaki; Koura, Seiko; Chung, Catherine; Tafazoli, Shahrzad; Roberts, Ashley

    2014-10-01

    The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study.

  2. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions.

    PubMed

    Itoh, Yuji; Hine, Kyoko; Miura, Hiroshi; Uetake, Tatsuo; Nakano, Masahiko; Takemura, Naohiro; Sakatani, Kaoru

    2016-01-01

    Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score<70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory.

  3. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions.

    PubMed

    Itoh, Yuji; Hine, Kyoko; Miura, Hiroshi; Uetake, Tatsuo; Nakano, Masahiko; Takemura, Naohiro; Sakatani, Kaoru

    2016-01-01

    Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score<70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory. PMID:26782228

  4. Phase conjugation by degenerate four wave mixing in disodium fluorescein solution in methanol

    NASA Technical Reports Server (NTRS)

    Abdeldayem, Hossin; Sekhar, P. Chandra; Venkateswarlu, P.; Geroge, M. C.

    1989-01-01

    Organic dyes are known to show the resonant type of nonlinear optical properties, including phase conjugation. In the present work, disodium fluorescein in methanol is used as an organic nonlinear medium for degenerate four wave mixing at 532 nm to see the intensity dependence of the phase conjugate signal at different concentrations of the solution. It is observed that the maximum reflectivity of the signal occurs in a concentration range of 5 x 10(exp -3)/cu cm to 1.2 x 10(exp -2) g/cu cm. It is also observed that the intensity of the signal drops suddenly to less than half of its maximum outside the concentration range mentioned above. An investigation of the phase conjugate signal intensity by changing the delay time between probe signal and the forward pump is also examined. Briefly discussed is the possibility of population grating in dye liquids as a source of enhancing the third order susceptibility besides the other techniques mentioned in reference. The experiment is done by beam splitting the second harmonic (532 nm) of Nd:YAG laser, Q-switched at 20 pulses/sec (pulse width is approximately 8 and 200 mJ per pulse).

  5. Elasticity, viscosity, and orientational fluctuations of a lyotropic chromonic nematic liquid crystal disodium cromoglycate.

    PubMed

    Zhou, Shuang; Neupane, Krishna; Nastishin, Yuriy A; Baldwin, Alan R; Shiyanovskii, Sergij V; Lavrentovich, Oleg D; Sprunt, Samuel

    2014-09-14

    Using dynamic light scattering, we study orientational fluctuation modes in the nematic phase of a self-assembled lyotropic chromonic liquid crystal (LCLC) disodium cromoglycate and measure the Frank elastic moduli and viscosity coefficients. The elastic moduli of splay (K1) and bend (K3) are in the order of 10 pN while the twist modulus (K2) is an order of magnitude smaller. The splay constant K1 and the ratio K1/K3 both increase substantially as the temperature T decreases, which we attribute to the elongation of the chromonic aggregates at lower temperatures. The bend viscosity is comparable to that of thermotropic liquid crystals, while the splay and twist viscosities are several orders of magnitude larger. The temperature dependence of bend viscosity is weak. The splay and twist viscosities change exponentially with the temperature. In addition to the director modes, the fluctuation spectrum reveals an additional mode that is attributed to diffusion of structural defects in the column-like aggregates.

  6. Hypertrophic Osteoarthropathy Presenting as Unilateral Cellulitis with Successful Treatment Using Pamidronate Disodium

    PubMed Central

    Bernardo, Sebastian G.; Burnett, Mark E.; Gordon, Marsha

    2012-01-01

    Hypertrophic pulmonary osteoarthropathy is a paraneoplastic syndrome seen in patients with lung cancer. This condition is characterized by the presence of digital clubbing, periosteal thickening, synovial thickening, and severe pain of the affected joints. Other syndromes exhibiting clubbing may or may not have underlying diseases causing their manifestation. An example is primary hypertrophic osteoarthropathy, or pachydermoperiostosis. While clubbing makes up part of the clinical picture in both hypertrophic pulmonary osteoarthropathy and hypertrophic osteoarthropathy, the latter has no underlying disease associations. Rather, primary hypertrophic osteoarthropathy is familial, idiopathic, and has a chronic course often beginning during puberty in males. Secondary hypertrophic osteoarthropathy is an acquired form of clubbing that is classically associated with lung disease. However, it has also been associated with diseases of the heart, liver, and intestines. In the setting of pulmonary malignancy, secondary hypertrophic osteoarthropathy is known as hypertrophic pulmonary osteoarthropathy. Hypertrophic pulmonary osteoarthropathy has a distinct constellation of clinical findings that includes intractable pain often refractory to treatments other than resolution of the underlying disease process. The authors herein report a case of hypertrophic pulmonary osteoarthropathy masquerading as recurrent lower extremity cellulitis with chronic hand and foot pain in the setting of pulmonary malignancy that responded dramatically to intravenous pamidronate disodium (a bisphosphonate). Given the rarity of hypertrophic osteoarthropathy associated with lung cancer and the difficulty with pain management in such circumstances, the authors present the following case in which pain was mitigated by treatment with bisphosphonate therapy. PMID:23050033

  7. Phase behavior of chromonic liquid crystal mixtures of Sunset Yellow and Disodium Cromoglycate

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Akihiro; Smith, Gregory; Yi, Youngwoo; Xu, Charles; Biffi, Silvia; Serra, Francesca; Bellini, Tommaso; Clark, Noel

    2014-03-01

    Chromonic liquid crystals (CLCs) are formed when planar molecules dissolved in water stack into rod-like aggregates that can order as liquid crystals. Isotropic, nematic, and M-phases can be observed depending on the degree of molecular orientational and positional order by variation of the CLC concentration. We focused on mixtures of two well-known CLCs, Sunset Yellow, a food dye, and disodium cromoglycate (DSCG), an asthma medication. In order to study the phase behaviors of these mixtures, we observed their textures in glass cells and capillaries using polarized light microscopy. We report here a ternary phase diagram describing the complete phase behavior of the CLC mixtures. We observed a variety of phase behaviors depending on species ratio and concentration. In the isotropic phase, no clear phase separation of the two dyes was observed, while separation did occur in many nematic and M-phase combinations. We will also describe phase observations made using a light spectroscopy and bulk centrifugal partitioning. Grant support: NSF DMR 1207606 and NSF MRSEC DMR-0820579.

  8. Inhaled disodium cromoglycate (DSCG) as maintenance therapy in children with asthma: a systematic review

    PubMed Central

    Tasche, M; Uijen, J; Bernsen, R; de Jongste, J C; van der Wouden, J C

    2000-01-01

    BACKGROUND—Disodium cromoglycate (DSCG) is included in the BTS guidelines on the treatment of asthma for use in children, but is now used only infrequently. We have identified and interpreted the findings of all published randomised, placebo controlled trials of DSCG in the prophylactic treatment of children with asthma.
METHODS—Several databases were searched to identify trials. Studies were included if they investigated subjects with asthma aged 0-18 years old, addressed maintenance treatment with inhaled DSCG, and were published in English. The methodological quality of the studies was assessed independently by three reviewers. The 95% confidence intervals (CI) of differences in the treatment effect for cough and wheeze between placebo and treatment with DSCG were computed. The estimates were pooled and tested for homogeneity and, to assess possible publication bias, a funnel plot was made and tested for symmetry.
RESULTS—Of the 24 randomised, placebo controlled trials identified, the methodological scores varied widely. The null hypothesis of homogeneity was rejected. Under the assumption of heterogeneity the overall CI for wheeze was 0.11 to 0.26 and for cough was 0.13to 0.27. The overall tolerance intervals (-0.11 to 0.48 and -0.04 to 0.43 for wheeze and cough, respectively) both included zero, so it cannot be concluded that future studies will show an effect of DSCG compared with placebo. Older studies were more often in favour of DSCG. The funnel plots suggest publication bias; small studies with negative or equal outcomes are lacking.
CONCLUSION—Given the apparent publication bias, the small overall treatment effect, and the tolerance interval including zero, there is insufficient evidence that DSCG has a beneficial effect as maintenance treatment in children with asthma.

 PMID:11050259

  9. Disodium cromoglycate enhances ongoing immunoglobulin production in vitro in human B cells.

    PubMed Central

    Kimata, H; Yoshida, A; Ishioka, C; Mikawa, H

    1991-01-01

    The effect of disodium cromoglycate (DSCG) upon human immunoglobulin (Ig) isotypes and IgG subclasses production by purified B cells was studied. DSCG enhanced IgM, IgG1, IgG2, IgG3, IgG4 and IgA production in a dose-dependent fashion, while DSCG failed to induce IgE production at any concentrations tested by purified B cells. When B cells were separated into small resting and large activated B cells, DSCG failed to induce Ig production from small resting B cells in the presence or absence of Staphylococcus aureus Cowan strain I (SAC). In contrast, in large activated B cells DSCG significantly enhanced all types of Ig production (two-to threefold), especially IgG4 production (seven-to 11-fold), except IgE, which large B cells did not produce. The enhancement of IgG subclass production was not subclass switching, since DSCG failed to enhance IgG1 production in B cells depleted of surface IgG1+ cells (sIgG1+ cells). Similarly, DSCG did not enhance IgG2, IgG3 or IgG4 production from sIgG2-, sIgG3- or sIgG4- B cells, respectively, Interleukin-4 (IL-4) or interleukin-6 (IL-6) also enhanced Ig production except IgG4 from large activated B cells. The enhancing effect of DSCG was not mediated by IL-4 or IL-6 since anti-IL-4 or anti-IL-6 antibody failed to block the DSCG-induced enhancement. DSCG also enhanced IgG2 and IgM production from human B-cell lines GM-1500 and CBL, respectively. These results suggest that DSCG directly and preferentially stimulates activated B cells which are producing Ig and, in addition, enhances their Ig production. PMID:1904400

  10. Effects of Pyrroloquinoline Quinone Disodium Salt Intake on the Serum Cholesterol Levels of Healthy Japanese Adults.

    PubMed

    Nakano, Masahiko; Kawasaki, Yuuki; Suzuki, Naoko; Takara, Tsuyoshi

    2015-01-01

    Pyrroloquinoline quinone (PQQ) is a water-soluble quinone compound that has a strong anti-oxidant capacity. A previous study in rats fed a PQQ-depleted diet showed that elevated levels of serum triglyceride (TG) decreased after PQQ supplementation. However, there is only one study reporting the effects of PQQ on serum lipid levels, such as those of TG and cholesterol, in humans. In this study, the effects of PQQ disodium salt (BioPQQ™) on serum TG and cholesterol levels in humans after 6 and 12 wk of treatment at an oral dosage of 20 mg/d were examined. This trial was conducted according to a randomized, placebo-controlled, double-blinded protocol. A total of 29 healthy Japanese adults, ranging from 40 to 57 y old, with normal to moderately high TG levels (110-300 mg/dL) as measured by a recent blood examination, were included in this study. In eleven volunteers out of 29, serum low-density lipoprotein cholesterol (LDL-chol) levels at baseline were high (≥140 mg/dL). After 12 wk, the mean serum TG levels had not changed; however, a marginally significant decrease in the mean LDL-chol (from 136.1 to 127.0 mg/dL) was observed in the PQQ group. In the stratification analysis of the high LDL-chol subgroup (baseline LDL-chol level ≥140 mg/dL), the mean LDL-chol levels decreased significantly from the baseline values in the PQQ group compared to the placebo group. Our study findings suggest that PQQ suppressed the LDL-chol level, which is an important finding, because a high level of this lipid is a risk factor for various lifestyle-related diseases.

  11. Inhaled steroids compared with disodium cromoglycate in preschool children with episodic viral wheeze.

    PubMed

    De Baets, F; Van Daele, S; Franckx, H; Vinaimont, F

    1998-06-01

    In school children with atopic asthma the beneficial effects of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDP) are well-established. In preschool children, wheezing is quite common, and in the majority of cases the symptoms are episodic and reported to be associated with viral infections rather than atopy. We compared the efficacy of regular treatment with DSCG and BDP for prevention of wheezing in preschool children. We were interested to establish whether regular treatment with inhaled anti-inflammatory drugs could lead to a decrease in bronchial responsiveness. In 15 patients (median age, 56 months; range, 43-66 months) bronchial responsiveness was assessed by measuring specific airway resistance (sRaw) during a histamine provocation test. The concentration of histamine eliciting a 100% increase in sRaw (PC100his) was determined. In a double-blind crossover study, patients inhaled either DSCG 10 mg three times a day or BDP 100 microg three times a day for 2 months. After a wash-out period, treatment was changed to BDP or DSCG, respectively. Daily peak flow measurements were carried out, and exacerbations were noted. PC100his was measured at the start and end of each treatment period. No significant decrease in bronchial responsiveness was seen (PC100his DSCG: before 1.3, after 1.66 mg/ml, Pvalue not significant; BDP: before 1.1 after 1.22 mg/ml, Pvalue not significant). Significantly higher morning peak flows were observed on BDP therapy (160 on BDP vs. 150 L/min on DSCG, P < 0.03). BDP treatment resulted in significantly fewer wheezing exacerbations (7 vs. 16, P < 0.005) compared with DSCG therapy. We conclude that in preschool children with episodic virally induced wheezing, BDP therapy was superior to DSCG aerosol treatments for the prevention of exacerbations of wheezing, although no significant effect on bronchial responsiveness was noted during either treatment protocol.

  12. Chronic vanadium poisoning in calves and its treatment with calcium disodium ethylenediaminetetraacetate.

    PubMed

    Gummow, B; Botha, C J; Williams, M C

    2006-10-01

    Sixteen Friesland heifer calves aged between 96 and 157 days were removed from a dairy farm that had been polluted with vanadium and randomly allocated into two equal groups (n = 8). The objective of the trial was to determine whether calcium disodium ethylenediaminetetraacetate (CaNa(2)EDTA) could be used as a treatment for cattle running in environments high in background vanadium. The treatment group received 80 mg CaNa(2)EDTA per kg body weight intraperitonealy (i.p.) twice a week over a 10-week period. The control group received normal saline i.p. over the same period. During the trial calves were exposed to a daily intake of vanadium in the form of contaminated tef hay derived from the farm of origin. In addition, the total mixed ration was spiked with a further 20 mg V(2)O(5)/kg feed to compensate for possible on-farm inhalation exposure. A stochastic model was used to estimate daily intake of vanadium as a distribution function. The model estimated that the daily intake of vanadium varied between an absolute minimum of 33 mg/day to an absolute maximum of 124 mg/day. The average intake of vanadium was 71.8 mg per day per calf. Various chemical pathology parameters were measured throughout the trial as well as urine excretion rates of vanadium and lymphocyte stimulation counts. All calves were slaughtered and necropsied in cohorts of 4-6 animals at monthly intervals after completion of the trial and withdrawal of vanadium from the ration. Tissue concentrations of vanadium were determined and necropsy findings were noted. The study found that CaNa(2)EDTA appears to enhance the excretion of vanadium in calves, but could not prove that the treatment had a protective effect against vanadium exposure. Calves were able to tolerate the prolonged treatment with CaNa(2)EDTA without side-effects.

  13. 18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways.

    PubMed

    Huang, Yi-Chang; Kuo, Chao-Lin; Lu, Kung-Wen; Lin, Jen-Jyh; Yang, Jiun-Long; Wu, Rick Sai-Chuen; Wu, Ping-Ping; Chung, Jing-Gung

    2016-01-01

    In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18α-glycyrrhetinic acid (18α-GA). Cells were exposed to 18α-GA at various concentrations for various time periods and were harvested for flow cytometry total viable cell and apoptotic cell death measurements. Cells treated with 18α-GA significantly inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner, with an IC50 value of 100 μM at 48 h. The cell growth inhibition resulted in induction of apoptosis and decreased the mitochondria membrane potential (ΔΨm) and increased caspase-8, -9 and -3 activities. Furthermore, cytochrome c and AIF were released from mitochondria, as shown by western blotting and confirmed by confocal laser microscopy. Western blotting showed that 18α-GA increased the levels of pro-apoptotic proteins such as Bax and Bid and decreased the anti-apoptotic proteins such as Bcl-2 and Bcl-xl, furthermore, results also showed that 18α-GA increased Fas and Fas-L which are associated with surface death receptor in HL-60 cells. Based on those observations, the present study supports the hypothesis that 18α-GA-induced apoptosis in HL-60 cells involves the activation of the both extrinsic and intrinsic apoptotic pathways. PMID:27376261

  14. The Protective Effects of Isoliquiritigenin and Glycyrrhetinic Acid against Triptolide-Induced Oxidative Stress in HepG2 Cells Involve Nrf2 Activation

    PubMed Central

    Cao, Ling-Juan; Li, Huan-De; Yan, Miao; Li, Zhi-Hua; Gong, Hui; Jiang, Pei; Deng, Yang; Fang, Ping-Fei; Zhang, Bi-Kui

    2016-01-01

    Triptolide (TP), an active ingredient of Tripterygium wilfordii Hook f., possesses a wide range of biological activities. Oxidative stress likely plays a role in TP-induced hepatotoxicity. Isoliquiritigenin (ISL) and glycyrrhetinic acid (GA) are potent hepatoprotection agents. The aim of the present study was to investigate whether Nrf2 pathway is associated with the protective effects of ISL and GA against TP-induced oxidative stress or not. HepG2 cells were treated with TP (50 nM) for 24 h after pretreatment with ISL and GA (5, 10, and 20 μM) for 12 h and 24 h, respectively. The results demonstrated that TP treatment significantly increased ROS levels and decreased GSH levels. Both ISL and GA pretreatment decreased ROS and meanwhile enhanced intracellular GSH content. Additionally, TP treatment obviously decreased the protein expression of Nrf2 and its target genes including HO-1 and MRP2 except NQO1. Moreover, both ISL and GA displayed activities as inducers of Nrf2 and increased the expression of HO-1, NQO1, and MRP2. Taken together the current data confirmed that ISL and GA could activate the Nrf2 antioxidant response in HepG2 cells, increasing the expression of its target genes which may be partly associated with their protective effects in TP-induced oxidative stress. PMID:26904149

  15. Validation protocol of analytical procedures for quantification of drugs in polymeric systems for parenteral administration: dexamethasone phosphate disodium microparticles.

    PubMed

    Martín-Sabroso, Cristina; Tavares-Fernandes, Daniel Filipe; Espada-García, Juan Ignacio; Torres-Suárez, Ana Isabel

    2013-12-15

    In this work a protocol to validate analytical procedures for the quantification of drug substances formulated in polymeric systems that comprise both drug entrapped into the polymeric matrix (assay:content test) and drug released from the systems (assay:dissolution test) is developed. This protocol is applied to the validation two isocratic HPLC analytical procedures for the analysis of dexamethasone phosphate disodium microparticles for parenteral administration. Preparation of authentic samples and artificially "spiked" and "unspiked" samples is described. Specificity (ability to quantify dexamethasone phosphate disodium in presence of constituents of the dissolution medium and other microparticle constituents), linearity, accuracy and precision are evaluated, in the range from 10 to 50 μg mL(-1) in the assay:content test procedure and from 0.25 to 10 μg mL(-1) in the assay:dissolution test procedure. The robustness of the analytical method to extract drug from microparticles is also assessed. The validation protocol developed allows us to conclude that both analytical methods are suitable for their intended purpose, but the lack of proportionality of the assay:dissolution analytical method should be taken into account. The validation protocol designed in this work could be applied to the validation of any analytical procedure for the quantification of drugs formulated in controlled release polymeric microparticles.

  16. 18α-Glycyrrhetinic acid lethality for neuroblastoma cells via de-regulating the Beclin-1/Bcl-2 complex and inducing apoptosis.

    PubMed

    Rahman, Md Ataur; Bishayee, Kausik; Habib, Khadija; Sadra, Ali; Huh, Sung-Oh

    2016-10-01

    18α-Glycyrrhetinic acid (18-GA) is a known gap-junction inhibitor with demonstrated anticancer effects. However, the different modes of cell cytotoxicity for 18-GA remain to be characterized. In this study, 18-GA reduced the expression of cell-cell interaction proteins (N- and VE-cadherin), and led to a dose-dependent increase in cytotoxicity of the neuroblastoma cells tested, but was less toxic toward actively dividing human embryonic kidney cells. We found that 18-GA could induce both autophagy and apoptosis. 18-GA mediated autophagy was due to accumulation of Atg5, Atg7 and LC3II and degradation of p62. Individual siRNAs against Atg5 and Atg7 prevented autophagy and resulted in a further loss of viability with 18-GA. In addition, combination of 18-GA with autophagy inhibitor chloroquine produced a more significant cell death. This implied a pro-survival function for autophagy induction with 18-GA. 18-GA also led to the destabilization of Bcl-2/Beclin-1 interaction and cleavage of Beclin-1, a protein known to play role in apoptosis and autophagy induction. Treatment of cells by a pan-caspase inhibitor or a caspase-3 siRNA prevented a large portion of 18-GA mediated cytotoxicity, demonstrating that caspase-dependent apoptosis induction was responsible for most of the observed cytotoxicity. In terms of signaling, 18-GA led to reduced phosphorylation of all three classes of MAP kinases. Taken together, 18-GA or its pathways may lead to more effective, targeted therapeutics against neuroblastoma.

  17. 18α-Glycyrrhetinic acid lethality for neuroblastoma cells via de-regulating the Beclin-1/Bcl-2 complex and inducing apoptosis.

    PubMed

    Rahman, Md Ataur; Bishayee, Kausik; Habib, Khadija; Sadra, Ali; Huh, Sung-Oh

    2016-10-01

    18α-Glycyrrhetinic acid (18-GA) is a known gap-junction inhibitor with demonstrated anticancer effects. However, the different modes of cell cytotoxicity for 18-GA remain to be characterized. In this study, 18-GA reduced the expression of cell-cell interaction proteins (N- and VE-cadherin), and led to a dose-dependent increase in cytotoxicity of the neuroblastoma cells tested, but was less toxic toward actively dividing human embryonic kidney cells. We found that 18-GA could induce both autophagy and apoptosis. 18-GA mediated autophagy was due to accumulation of Atg5, Atg7 and LC3II and degradation of p62. Individual siRNAs against Atg5 and Atg7 prevented autophagy and resulted in a further loss of viability with 18-GA. In addition, combination of 18-GA with autophagy inhibitor chloroquine produced a more significant cell death. This implied a pro-survival function for autophagy induction with 18-GA. 18-GA also led to the destabilization of Bcl-2/Beclin-1 interaction and cleavage of Beclin-1, a protein known to play role in apoptosis and autophagy induction. Treatment of cells by a pan-caspase inhibitor or a caspase-3 siRNA prevented a large portion of 18-GA mediated cytotoxicity, demonstrating that caspase-dependent apoptosis induction was responsible for most of the observed cytotoxicity. In terms of signaling, 18-GA led to reduced phosphorylation of all three classes of MAP kinases. Taken together, 18-GA or its pathways may lead to more effective, targeted therapeutics against neuroblastoma. PMID:27520483

  18. In vivo percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in humans: a summary.

    PubMed

    Wester, R C; Hui, X; Maibach, H I; Bell, K; Schell, M J; Northington, D J; Strong, P; Culver, B D

    1998-01-01

    Literature from the first half of this century reports concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry, which now allows quantitation of percutaneous absorption of 10B in 10B-enriched boric acid, borax, and disodium octaborate tetrahydrate (DOT) in biological matrices. This made it possible, in the presence of comparatively large natural dietary boron intakes for the in vivo segment of this study, to quantify the boron passing through skin. Human volunteers were dosed with 10B-enriched boric acid, 5.0%, borax, 5.0%, or disodium octaborate tetrahydrate, 10% in aqueous solutions. Urinalysis, for boron and changes in boron isotope ratios, was used to measure absorption. Boric acid in vivo percutaneous absorption was 0.226 (SD = 0.125) mean percent dose, with flux and permeability constant (Kp) calculated at 0.009 microg/cm2/h and 1.9 x 10(-7) cm/h, respectively. Borax absorption was 0.210 (SD = 0.194) mean percent dose, with flux and Kp calculated at 0.009 microg/cm2/h and 1.8 x 10(-7) cm/h, respectively. DOT absorption was 0.122 (SD = 0.108) mean percent, with flux and Kp calculated at 0.01 microg/cm2/h and 1.0 x 10(-7) cm/h, respectively. Pretreatment with the potential skin irritant 2% sodium lauryl sulfate had no effect on boron skin absorption. These in vivo results show that percutaneous absorption of boron, as boric acid, borax, and disodium octaborate tetrahydrate, through intact human skin is low and is significantly less than the average daily dietary intake. This very low boron skin absorption makes it apparent that, for the borates tested, the use of gloves to prevent systemic uptake is unnecessary. These findings do not apply to abraded or otherwise damaged skin.

  19. Theoretical studies of the local structure and EPR parameters for Cu2+ centers in disodium malonate trihydrate single crystal

    NASA Astrophysics Data System (ADS)

    Chao-Ying, Li; Ying, Huang; Xue-Mei, Zheng

    2015-01-01

    The electron paramagnetic resonance (EPR) parameters (g factors gxx, gyy, gzz and hyperfine structure constants Axx, Ayy, Azz) of the two Cu2+ centers in disodium malonate trihydrate (DSMT) single crystal are theoretically interpreted using the high order perturbation formulas of these parameters for a 3d9 ions in rhombically elongated octahedra. In the calculation, the rhombic crystal-field parameters are determined from the superposition model and the admixture of d-orbitals in the ground state wave function are taking account, the results show that although the admixture of the | d z 2 > state to the ground state wave function is small, it should not be neglected in calculations of the EPR parameters. The theoretical EPR parameters show good agreement with the observed values. The results are discussed.

  20. Disodium hydrogen citrate sesquihydrate, Na2HC6H5O7(H2O)1.5.

    PubMed

    Rammohan, Alagappa; Sarjeant, Amy A; Kaduk, James A

    2016-07-01

    The crystal structure of disodium hydrogen citrate sesquihydrate, 2Na2 (+)·C6H6O7 (2-)·1.5H2O, has been solved and refined using laboratory X-ray single-crystal diffraction data, and optimized using density functional techniques. The asymmetric unit contains two independent hydrogen citrate anions, four sodium cations and three water molecules. The coordination polyhedra of the cations (three with a coordination number of six, one with seven) share edges to form isolated 8-rings. The un-ionized terminal carb-oxy-lic acid groups form very strong hydrogen bonds to non-coordinating O atoms, with O⋯O distances of 2.46 Å. PMID:27555936

  1. Disodium hydrogen citrate sesquihydrate, Na2HC6H5O7(H2O)1.5

    PubMed Central

    Rammohan, Alagappa; Sarjeant, Amy A.; Kaduk, James A.

    2016-01-01

    The crystal structure of disodium hydrogen citrate sesquihydrate, 2Na2 +·C6H6O7 2−·1.5H2O, has been solved and refined using laboratory X-ray single-crystal diffraction data, and optimized using density functional techniques. The asymmetric unit contains two independent hydrogen citrate anions, four sodium cations and three water molecules. The coordination polyhedra of the cations (three with a coordination number of six, one with seven) share edges to form isolated 8-rings. The un-ionized terminal carb­oxy­lic acid groups form very strong hydrogen bonds to non-coordinating O atoms, with O⋯O distances of 2.46 Å. PMID:27555936

  2. The liquorice root derivative glycyrrhetinic acid can ameliorate ionoregulatory disturbance in rainbow trout (Oncorhynchus mykiss) abruptly exposed to ion-poor water.

    PubMed

    Chen, Chun Chih; Kolosov, Dennis; Kelly, Scott P

    2016-09-01

    To consider the idea that a dietary botanical supplement could act as an adaptogen in a teleost fish, the effect of a liquorice root derivative (18β-glycyrrhetinic acid, 18βGA) on rainbow trout following an acute ionoregulatory stressor was examined. Freshwater (FW) trout were fed a control or 18βGA supplemented diet (0, 5, or 50μg 18βGA/g diet) for 2weeks, then abruptly exposed to ion-poor water (IPW) for 24h. Following IPW exposure, muscle moisture content and serum cortisol levels elevated and serum [Na(+)] and/or [Cl(-)] reduced in control and 50μg/g 18βGA-fed fish. However, these endpoints were unaltered in 5μg/g 18βGA-fed fish. Gill tissue was investigated for potential mechanisms of 18βGA action by examining mRNA abundance of genes encoding corticosteroid receptors (CRs), 11β-hydroxysteroid dehydrogenase 2 (11β-hsd2), and tight junction (TJ) proteins, as well as Na(+)-K(+)-ATPase and H(+)-ATPase activity, and mitochondrion-rich cell (MRC) morphometrics. Following IPW exposure, CR and 11β-hsd2 mRNA, MRC fractional surface, Na(+)-K(+)-ATPase and H(+)-ATPase activity were unaltered or decreased in 50μg 18βGA fish, as was mRNA encoding select TJ proteins. In contrast, 5μg 18βGA-fed fish exhibited elevated 11β-hsd2 and CR mRNA abundance versus 50μg 18βGA-fed, and reduced MRC apical area as well as some differences in TJ protein mRNA abundance versus control fish. Data suggest that 18βGA, at low levels, may be adaptogenic in trout and might help to ameliorate ionoregulatory perturbation following IPW exposure. This seems to occur, in part, through 18βGA-induced alterations in the biochemistry and physiology of the gill.

  3. The liquorice root derivative glycyrrhetinic acid can ameliorate ionoregulatory disturbance in rainbow trout (Oncorhynchus mykiss) abruptly exposed to ion-poor water.

    PubMed

    Chen, Chun Chih; Kolosov, Dennis; Kelly, Scott P

    2016-09-01

    To consider the idea that a dietary botanical supplement could act as an adaptogen in a teleost fish, the effect of a liquorice root derivative (18β-glycyrrhetinic acid, 18βGA) on rainbow trout following an acute ionoregulatory stressor was examined. Freshwater (FW) trout were fed a control or 18βGA supplemented diet (0, 5, or 50μg 18βGA/g diet) for 2weeks, then abruptly exposed to ion-poor water (IPW) for 24h. Following IPW exposure, muscle moisture content and serum cortisol levels elevated and serum [Na(+)] and/or [Cl(-)] reduced in control and 50μg/g 18βGA-fed fish. However, these endpoints were unaltered in 5μg/g 18βGA-fed fish. Gill tissue was investigated for potential mechanisms of 18βGA action by examining mRNA abundance of genes encoding corticosteroid receptors (CRs), 11β-hydroxysteroid dehydrogenase 2 (11β-hsd2), and tight junction (TJ) proteins, as well as Na(+)-K(+)-ATPase and H(+)-ATPase activity, and mitochondrion-rich cell (MRC) morphometrics. Following IPW exposure, CR and 11β-hsd2 mRNA, MRC fractional surface, Na(+)-K(+)-ATPase and H(+)-ATPase activity were unaltered or decreased in 50μg 18βGA fish, as was mRNA encoding select TJ proteins. In contrast, 5μg 18βGA-fed fish exhibited elevated 11β-hsd2 and CR mRNA abundance versus 50μg 18βGA-fed, and reduced MRC apical area as well as some differences in TJ protein mRNA abundance versus control fish. Data suggest that 18βGA, at low levels, may be adaptogenic in trout and might help to ameliorate ionoregulatory perturbation following IPW exposure. This seems to occur, in part, through 18βGA-induced alterations in the biochemistry and physiology of the gill. PMID:27220746

  4. Non-focal liver signal abnormalities on hepatobiliary phase of gadoxetate disodium-enhanced MR imaging: a review and differential diagnosis.

    PubMed

    Furlan, Alessandro; Borhani, Amir A; Heller, Matthew T; Yu, Robinson K; Tublin, Mitchell E

    2016-07-01

    Gadoxetate disodium (Gd-EOB-DTPA) is a linear, non-ionic paramagnetic MR contrast agent with combined extracellular and hepatobiliary properties commonly used for several liver indications. Although gadoxetate disodium is commonly used for detection and characterization of focal lesions, a spectrum of diffuse disease processes can affect the hepatobiliary phase of imaging (i.e., when contrast accumulates within the hepatocytes). Non-focal signal abnormalities during the hepatobiliary phase can be seen with multiple disease processes such as deposition disorders, infiltrating tumors, vascular diseases, and post-treatment changes. The purpose of this paper is to review the different processes which result in non-focal signal alteration during the hepatobiliary phase and to describe imaging patterns that may order a differential diagnosis and facilitate patient management. PMID:26907715

  5. EDTA disodium zinc has superior bioavailability compared to common inorganic or chelated zinc compounds in rats fed a high phytic acid diet.

    PubMed

    Bertinato, Jesse; Sherrard, Lindsey; Plouffe, Louise J

    2012-10-01

    Different zinc (Zn) compounds have unique properties that may influence the amount of Zn absorbed particularly in the presence of phytic acid (PA), a common food component that binds Zn and decreases its bioavailability. In this study, 30-day-old male rats (n=12/diet group) were fed diets supplemented with PA (0.8%) and low levels (8mg Zn/kg diet) of inorganic (Zn oxide, Zn sulphate) or chelated (Zn gluconate, Zn acetate, Zn citrate, EDTA disodium Zn, Zn orotate) Zn compounds for 5 weeks. Two control groups were fed diets supplemented with low or normal (30mg Zn/kg diet) Zn (as Zn oxide) without added PA. Control rats fed the low Zn oxide diet showed depressed Zn status. Addition of PA to this diet exacerbated the Zn deficiency in rats. Growth (body weight gain and femur length) and Zn concentrations in plasma and tissues were similar in rats fed Zn oxide, Zn sulphate, Zn gluconate, Zn acetate, Zn citrate or Zn orotate. Rats fed EDTA disodium Zn showed enhanced growth compared to rats fed Zn oxide or Zn gluconate and had higher Zn concentrations in plasma and femur compared to rats fed all other Zn compounds. Only the haematological profile of rats fed EDTA disodium Zn did not differ from control rats fed normal Zn. These data indicate that in rats fed a high PA diet, bioavailability of commonly used inorganic or chelated Zn compounds does not differ appreciably, but Zn supplied as an EDTA disodium salt has superior bioavailability.

  6. Distance measurements in disodium ATP hydrates by means of 31P double quantum two-dimensional solid-state NMR spectroscopy

    NASA Astrophysics Data System (ADS)

    Potrzebowski, M. J.; Gajda, J.; Ciesielski, W.; Montesinos, I. M.

    2006-04-01

    POST-C7 measurements provide constraints allowing distinguishing crystal lattice organization and establishing intra and/or intermolecular distances between phosphorus atoms of triphosphate chains for different hydrates of disodium ATP salts. Double-quantum efficiency in function of excitation time obtained from series of two-dimensional spectra for POST-C7 experiments was used to set up of buildup curves and semi-quantitative measure of 31P- 31P length.

  7. Effect of the Food Additives Sodium Citrate and Disodium Phosphate on Shiga Toxin-Producing Escherichia coli and Production of stx-Phages and Shiga toxin.

    PubMed

    Lenzi, Lucas J; Lucchesi, Paula M A; Medico, Lucía; Burgán, Julia; Krüger, Alejandra

    2016-01-01

    Induction and propagation of bacteriophages along the food production chain can represent a significant risk when bacteriophages carry genes for potent toxins. The aim of this study was to evaluate the effect of different compounds used in the food industry on the growth of Shiga toxin-producing Escherichia coli (STEC) and the production of stx-phage particles and Shiga toxin. We tested the in vitro effect of lactic acid, acetic acid, citric acid, disodium phosphate, and sodium citrate on STEC growth. A bacteriostatic effect was observed in most of treated cultures. The exceptions were those treated with sodium citrate and disodium phosphate in which similar growth curves to the untreated control were observed, but with reduced OD600 values. Evaluation of phage production by plaque-based assays showed that cultures treated with sodium citrate and disodium phosphate released phages in similar o lower levels than untreated cultures. However, semi-quantification of Stx revealed higher levels of extracellular Stx in STEC cultures treated with 2.5% sodium citrate than in untreated cultures. Our results reinforce the importance to evaluate if additives and other treatments used to decrease bacterial contamination in food induce stx-phage and Stx production. PMID:27446032

  8. Effect of the Food Additives Sodium Citrate and Disodium Phosphate on Shiga Toxin-Producing Escherichia coli and Production of stx-Phages and Shiga toxin.

    PubMed

    Lenzi, Lucas J; Lucchesi, Paula M A; Medico, Lucía; Burgán, Julia; Krüger, Alejandra

    2016-01-01

    Induction and propagation of bacteriophages along the food production chain can represent a significant risk when bacteriophages carry genes for potent toxins. The aim of this study was to evaluate the effect of different compounds used in the food industry on the growth of Shiga toxin-producing Escherichia coli (STEC) and the production of stx-phage particles and Shiga toxin. We tested the in vitro effect of lactic acid, acetic acid, citric acid, disodium phosphate, and sodium citrate on STEC growth. A bacteriostatic effect was observed in most of treated cultures. The exceptions were those treated with sodium citrate and disodium phosphate in which similar growth curves to the untreated control were observed, but with reduced OD600 values. Evaluation of phage production by plaque-based assays showed that cultures treated with sodium citrate and disodium phosphate released phages in similar o lower levels than untreated cultures. However, semi-quantification of Stx revealed higher levels of extracellular Stx in STEC cultures treated with 2.5% sodium citrate than in untreated cultures. Our results reinforce the importance to evaluate if additives and other treatments used to decrease bacterial contamination in food induce stx-phage and Stx production.

  9. Effect of the Food Additives Sodium Citrate and Disodium Phosphate on Shiga Toxin-Producing Escherichia coli and Production of stx-Phages and Shiga toxin

    PubMed Central

    Lenzi, Lucas J.; Lucchesi, Paula M. A.; Medico, Lucía; Burgán, Julia; Krüger, Alejandra

    2016-01-01

    Induction and propagation of bacteriophages along the food production chain can represent a significant risk when bacteriophages carry genes for potent toxins. The aim of this study was to evaluate the effect of different compounds used in the food industry on the growth of Shiga toxin-producing Escherichia coli (STEC) and the production of stx-phage particles and Shiga toxin. We tested the in vitro effect of lactic acid, acetic acid, citric acid, disodium phosphate, and sodium citrate on STEC growth. A bacteriostatic effect was observed in most of treated cultures. The exceptions were those treated with sodium citrate and disodium phosphate in which similar growth curves to the untreated control were observed, but with reduced OD600 values. Evaluation of phage production by plaque-based assays showed that cultures treated with sodium citrate and disodium phosphate released phages in similar o lower levels than untreated cultures. However, semi-quantification of Stx revealed higher levels of extracellular Stx in STEC cultures treated with 2.5% sodium citrate than in untreated cultures. Our results reinforce the importance to evaluate if additives and other treatments used to decrease bacterial contamination in food induce stx-phage and Stx production. PMID:27446032

  10. In vitro percutaneous absorption of boron as boric acid, borax, and disodium octaborate tetrahydrate in human skin: a summary.

    PubMed

    Wester, R C; Hartway, T; Maibach, H I; Schell, M J; Northington, D J; Culver, B D; Strong, P L

    1998-01-01

    Literature from the first half of this century reports concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry which now allows quantitation of percutaneous absorption of 10B in 10B-enriched boric acid, borax and disodium octaborate tetrahydrate (DOT) in biological matrices. In vitro human skin percent doses of boric acid absorbed were 1.2 for a 0.05% solution, 0.28 for a 0.5% solution, and 0.70 for a 5.0% solution. These absorption amounts translated into flux values of, respectively, 0.25, 0.58, and 14.58 microg/cm2/h, and permeability constants (Kp) of 5.0 x 10(-4), 1.2 x 10(-4), and 2.9 x 10(-4) cm/h for the 0.05%, 0.5%, and 5.0% solutions. The above in vitro doses were at infinite, 1000 microL/cm2 volume. At 2 microL/cm2 (the in vivo dosing volume), flux decreased some 200-fold to 0.07 microg/cm2/h and Kp of 1.4 x 10(-6) cm/h, while percent dose absorbed was 1.75%. Borax dosed at 5.0%/1000 microL/cm2 had 0.41 percent dose absorbed, flux at 8.5 microg/cm2/h, and Kp was 1.7 x 10(-4) cm/h. Disodium octaborate tetrahydrate (DOT) dosed at 10%/1000 microL/cm2 was 0.19 percent dose absorbed, flux at 7.9 microg/cm2/h, and Kp was 0.8 x 10(-4) cm/h. These in vitro results from infinite doses (1000 microL/cm2) were a 1000-fold greater than those obtained in the companion in vivo study. The results from the finite (2 microL/cm2) dosing were closer (10-fold difference) to the in vivo results. General application of infinite dose percutaneous absorption values for risk assessment is questioned by these results.

  11. Simultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, piperine and glycyrrhetinic acid in rat plasma by HPLC-MS/MS: application to a pharmacokinetic study of Longhu Rendan pills.

    PubMed

    Wang, Tianming; Ding, Liqing; Jin, Huajia; Shi, Rong; Li, Yuanyuan; Wu, Jiasheng; Li, Yifei; Zhu, Li; Ma, Yueming

    2016-08-01

    A sensitive, specific, accurate HPLC-MS/MS method was developed and validated for the simultaneous quantification of catechin, epicatechin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, piperine and glycyrrhetinic acid from Longhu Rendan pills in rat plasma. Chromatographic separation was performed with a Hypersil Gold C18 column using a gradient of methanol and 0.01% acetic acid containing 0.2 mm ammonium acetate as mobile phase. The analytes were quantified on a triple quadrupole mass spectrometer, operating in selected reaction monitoring mode and switching the electrospray ion source polarity between positive and negative modes in a single run. The calibration curves of catechin, epicatechin, liquiritin, isoliquiritin, liquiritigenin, isoliquiritigenin, piperine and glycyrrhetinic acid were linear over the concentration ranges of 5-2000, 5-2000, 0.5-200, 0.5-200, 0.25-100, 0.25-100, 0.025-10 and 0.50-200 ng mL(-1) , respectively. The intra- and inter-assay precisions and accuracies were <11.6 and 91.9-108.2%, respectively, for all analytes. Matrix effects for all analytes were between 88.2 and 114.2%. Stability testing showed that all analytes were stable in plasma at 24 °C for 3 h, at 4 °C for 24 h, after three freeze-thaw cycles, and at -80 °C for 15 days. The method was successfully applied to an in vivo study evaluating the pharmacokinetics of multiple nonvolatile compounds following intragastric administration of Longhu Rendan pills to rats. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Long-term Study of Disodium Cromoglycate in Treatment of Severe Extrinsic or Intrinsic Bronchial Asthma in Adults

    PubMed Central

    1972-01-01

    The results are reported here of a long-term double-blind controlled clinical trial of disodium cromoglycate (D.S.C.G.) and isoprenaline, D.S.C.G. alone, isoprenaline alone, and a placebo given as a powder for inhalation in the treatment of severe bronchial asthma. At the end of one year 16 out of 20 patients on D.S.C.G.-isoprenaline remained on the allocated capsules, compared with 10 out of 15 on D.S.C.G., 5 out of 20 on isoprenaline, and 3 out of 19 taking the placebo. The differences between each of the D.S.C.G.-isoprenaline and D.S.C.G. regimens compared with the isoprenaline and placebo regimens were statistically significant. After eight weeks on four capsules a day the patients in each group were allocated at random so that half continued on full dosage and half on a reducing regimen. At the end of the year there was no significant difference in the failure rate between patients allocated the full dosage and the patients on the reducing dosage. The capsules were well tolerated and toxicity to D.S.C.G. was not observed. PMID:4629183

  13. Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia

    PubMed Central

    Sharman, Jeff; Sweetenham, John; Johnston, Patrick B.; Vose, Julie M.; LaCasce, Ann; Schaefer-Cutillo, Julia; De Vos, Sven; Sinha, Rajni; Leonard, John P.; Cripe, Larry D.; Gregory, Stephanie A.; Sterba, Michael P.; Lowe, Ann M.; Levy, Ronald; Shipp, Margaret A.

    2010-01-01

    Certain malignant B cells rely on B-cell receptor (BCR)–mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095. PMID:19965662

  14. Disodium octaborate tetrahydrate treatments to slash pine for protection against formosan subterranean termite and eastern subterranean termite (isoptera: rhinotermitidae)

    SciTech Connect

    Mauldin, J.K.; Kard, B.M.

    1996-06-01

    Minimum retentions of disodium octaborate tetrahydrate (DOT) needed in slash pine, Pinus elliottii Engelm. variety elliottii, wood to provide maximum protection against 2 species of subterranean termites were determined in choice and no-choice laboratory tests. Efficacy criteria for DOT were greater or equal to 90% termite mortality and equal to or less than 5% loss in weight of treated wooden blocks. For termites fed only DOT-treated wood, 0.10 and 0.30% boric acid equivalent (BAE, percentage of boric acid based on dry weight of wood, assuming all boron is present as boric acid) protected wood from the eastern subterranean termite, Reticulitermes flavipes (Kollar), and Formosan subterranean termite, Coptotermes formosanus Shiraki, respectively. When termites had a choice between treated or nontreated wooden blocks were not in contact with soil or exposed to rain, a BAE of 0.30% protected the wood from naturally occuring Reticulitermes sp. for 18 mo. In wooden structures under constant pressure from subterranean termites, concentrations greater than 0.54% BAE may be required to protect wood, especially against C. formosanus.

  15. Exploring the sodium storage mechanism in disodium terephthalate as anode for organic battery using density-functional theory calculations

    NASA Astrophysics Data System (ADS)

    Sk, Mahasin Alam; Manzhos, Sergei

    2016-08-01

    We present an ab initio study of sodium storage mechanism in disodium terephthalate (Na2TP) which is a very promising anode material for organic sodium (Na)-ion batteries with reported experimental capacities of ∼255 mAh g-1, previously attributed to Na attachment to the two carboxylate groups (coordinating to oxygen atoms). We show here that the inserted Na atoms prefer to bind at carboxylate sites at low Na concentrations and are dominant for insertion of up to one Na atom per molecule; for higher Na concentrations, the hexagonal sites (on the aromatic ring) become dominant. We confirm that the Na2TP crystal can store a maximum of two Na atoms per molecule, as observed in experiments. Our current results are intriguing as we reveal that the Na binding at carboxylate sites contributes to the initial part of Na2TP sodiation curve and the Na binding at hexagonal sites contributes to the second part of the curve. The inserted Na atoms donate electrons to empty states in the conduction band. Moreover, we show that the Na diffusion barriers in clean Na2TP can be as low as 0.23 eV. We also show that there is significant difference in the mechanism of Na interaction between individual molecules and the crystal.

  16. Exploring the sodium storage mechanism in disodium terephthalate as anode for organic battery using density-functional theory calculations

    NASA Astrophysics Data System (ADS)

    Sk, Mahasin Alam; Manzhos, Sergei

    2016-08-01

    We present an ab initio study of sodium storage mechanism in disodium terephthalate (Na2TP) which is a very promising anode material for organic sodium (Na)-ion batteries with reported experimental capacities of ∼255 mAh g-1, previously attributed to Na attachment to the two carboxylate groups (coordinating to oxygen atoms). We show here that the inserted Na atoms prefer to bind at carboxylate sites at low Na concentrations and are dominant for insertion of up to one Na atom per molecule; for higher Na concentrations, the hexagonal sites (on the aromatic ring) become dominant. We confirm that the Na2TP crystal can store a maximum of two Na atoms per molecule, as observed in experiments. Our current results are intriguing as we reveal that the Na binding at carboxylate sites contributes to the initial part of Na2TP sodiation curve and the Na binding at hexagonal sites contributes to the second part of the curve. The inserted Na atoms donate electrons to empty states in the conduction band. Moreover, we show that the Na diffusion barriers in clean Na2TP can be as low as 0.23 eV. We also show that there is significant difference in the mechanism of Na interaction between individual molecules and the crystal.

  17. Influence of salt additives on phase transformation of guanosine 5-monophosphate disodium in anti-solvent crystallization

    NASA Astrophysics Data System (ADS)

    Nguyen, Anh-Tuan; Kang, Jeongki; Kim, Woo-Sik

    2013-06-01

    The influence of sodium chloride (NaCl) as an additive on the anti-solvent crystallization of guanosine 5-monophosphate disodium (GMP-2Na) was investigated in continuous Couette-Taylor (CT) and batch mixing tank (MT) crystallizers. The anti-solvent crystallization initially precipitated amorphous solids of GMP-2Na, which then slowly transformed into hydrate crystals in the solution. However, the phase transformation of GMP-2Na was markedly promoted by the sodium chloride additive due to the common ion effect. While the normal phase transformation in the batch MT crystallizer required over 120 min of crystallization time without using the sodium chloride additive, the process was completed within 60 min when a small amount of the salt additive was added. The phase transformation was also significantly accelerated in the continuous CT crystallizer. Without using the sodium chloride additive, 7 min of the mean residence time was required for the production of 100% hydrate GMP crystals. However, when using the sodium chloride additive, a mean residence time of only 2 min was sufficient to completely transform the amorphous solids of GMP-2Na into hydrate crystals due to the common ion effect combined with the effective fluid motion of the Taylor vortex for the mass transfer.

  18. Diagnostic capability of gadoxetate disodium-enhanced liver MRI for diagnosis of hepatocellular carcinoma: comparison with multi-detector CT.

    PubMed

    Toyota, Naoyuki; Nakamura, Yuko; Hieda, Masashi; Akiyama, Naoko; Terada, Hiroaki; Matsuura, Noriaki; Nishiki, Masayo; Kono, Hirotaka; Kohno, Hiroshi; Irei, Toshimitsu; Yoshikawa, Yukinobu; Kuraoka, Kazuya; Taniyama, Kiyomi; Awai, Kazuo

    2013-09-01

    The purpose of this study was to evaluate the diagnostic capability of gadoxetate disodium (Gd-EOB)-MRI for the detection of hepatocellular carcinoma (HCC) compared with multidetector CT (MDCT). Fifty patients with 57 surgically proven HCCs who underwent Gd-EOB-MRI and MDCT from March 2008 to June 2011 were evaluated. Two observers evaluated MR and CT on a lesion-by-lesion basis. We analyzed sensitivity by grading on a 5-point scale, the degree of arterial enhancement and the differences in histological grades in the diffusion-weighted images (DWI). The results showed that the sensitivity of Gd-EOB-MRI was higher than that of MDCT especially for HCCs that were 1 cm in diameter or smaller. The hepatobiliary phase was useful for the detecting of small HCC. We had few cases in which it was difficult to judge HCC in the arterial enhancement between MRI and MDCT. In the diffusion-weighted image, well differentiated HCC tended to show a low signal intensity, and poorly differentiated HCC tended to show a high signal intensity. In moderately differentiated HCC's, the mean diameter of the high signal intensity group was larger than that of the low signal intensity group (24.5 mm vs. 15.8 mm). In conclusion, Gd-EOB-MRI tended to show higher sensitivity compared to MDCT in the detection of HCC.

  19. Effects of dietary pyrroloquinoline quinone disodium on growth performance, carcass yield and antioxidant status of broiler chicks.

    PubMed

    Samuel, K G; Zhang, H J; Wang, J; Wu, S G; Yue, H Y; Sun, L L; Qi, G H

    2015-03-01

    Pyrroloquinoline quinone (PQQ), a putative essential nutrient and redox modulator in microorganisms, cell and animal models, has been recognized as a growth promoter in rodents. Growth performance, carcass yield and antioxidant status were evaluated on broiler chickens fed different levels of PQQ disodium (PQQ.Na2). A total of 784 day-old male Arbor Acres (AA) broilers were randomly allotted into seven dietary groups: negative control group (NC) fed a basal diet without virginiamycin (VIR) or PQQ.Na2; a positive control group (PC) fed a diet with 15 mg of VIR/kg diet; and PQQ.Na2 groups fed with 0.05, 0.10, 0.20, 0.40 or 0.80 mg PQQ.Na2/kg diet. Each treatment contained eight replicates with 14 birds each. The feeding trial lasted for 6 weeks. The results showed that chicks fed 0.2 mg PQQ.Na2/kg diet significantly improved growth performance comparable to those in PC group, and the feed efficiency enhancement effects of dietary PQQ.Na2 was more apparent in grower phase. Dietary addition of PQQ.Na2 had the potential to stimulate immune organs development, and low level dietary addition (<0.1 mg/kg) increased plasma lysozyme level. Broilers fed 0.2 mg PQQ.Na2/kg diet gained more carcasses at day 42, and had lower lipid peroxide malondialdehyde content and higher total antioxidant power in plasma. The results indicated that dietary PQQ.Na2 (0.2 mg/kg diet) had the potential to act as a growth promoter comparable to antibiotic in broiler chicks.

  20. Effect of disodium fumarate on microbial abundance, ruminal fermentation and methane emission in goats under different forage: concentrate ratios.

    PubMed

    Yang, C J; Mao, S Y; Long, L M; Zhu, W Y

    2012-11-01

    This study investigated the effects of disodium fumarate (DF) on methane emission, ruminal fermentation and microbial abundance in goats under different forage (F) : concentrate (C) ratios and fed according to maintenance requirements. Four ruminally fistulated, castrated male goats were used in a 4 × 4 Latin square design with a 2 × 2 factorial arrangement of treatments and the main factors being the F : C ratios (41 : 59 or 58 : 42) and DF supplementation (0 or 10 g/day). DF reduced methane production (P < 0.05) on average by 11.9%, irrespective of the F : C ratio. The concentrations of total volatile fatty acids, acetate and propionate were greater in the rumen of goats supplemented with DF (P < 0.05), whereas the abundance of methanogens was lower (P < 0.05). In high-forage diets, the abundance of Selenomonas ruminantium, a fumarate-reducing bacterium, was greater in the rumen of goats supplemented with DF. The abundance of fungi, protozoa, Ruminococus flavefaciens and Fibrobacter succinogenes were not affected by the addition of DF. Variable F : C ratios affected the abundance of methanogens, fungi and R. flavefaciens (P < 0.05), but did not affect methane emission. The result implied that DF had a beneficial effect on the in vivo rumen fermentation of the goats fed diets with different F : C ratios and that this effect were not a direct action on anaerobic fungi, protozoa and fibrolytic bacteria, the generally recognized fiber-degrading and hydrogen-producing microorganisms, but due to the stimulation of fumarate-reducing bacteria and the depression of methanogens.

  1. Disodium N,N-bis-(dithiocarboxy)ethanediamine: synthesis, performance, and mechanism of action toward trace ethylenediaminetetraacetic acid copper (II).

    PubMed

    Xiao, Xiao; Ye, Maoyou; Yan, Pingfang; Qiu, Yiqin; Sun, Shuiyu; Ren, Jie; Dai, Yongkang; Han, Dajian

    2016-10-01

    A new effective multi-dithiocarbamate heavy metal precipitant, disodium N,N-bis-(dithiocarboxy) ethanediamine (BDE), was synthesized by mixing ethanediamine with carbon disulfide under alkaline conditions, and it was utilized for removing trace ethylenediaminetetraacetic acid copper (II) (EDTA-Cu) from wastewater. Its structure was confirmed by ultraviolet spectra, Fourier transform infrared spectra, scanning electron microscopy, thermogravimetric analysis, and elemental analysis. The removal performance of EDTA-Cu by BDE was evaluated according to BDE dosage, initial concentration, pH, and reaction time through single-factor experiments. With the optimized conditions of a pH range of 3-9, dosage ratio of BDE/Cu of 1:1, PAM dosage of 1 mg/L, and reaction time of 4 min, the removal efficiency of Cu(2+) was more than 98 % from simulated wastewater containing EDTA-Cu with initial concentrations of 5-100 mg/L. Treatment of actual EDTA-Cu wastewater showed that BDE performed superior effectiveness, and the average residential concentration of Cu(2+) was 0.115 mg/L. Besides, the stability of chelated precipitate and the reaction mechanism of BDE and EDTA-Cu were also introduced. The toxicity characteristic leaching procedure (TCLP) and semi-dynamic leaching test (SDLT) indicated that the chelated precipitate was non-hazardous and stable in weak acid and alkaline conditions. The BDE reacts with EDTA-Cu at a stoichiometric ratio, and the removal of Cu(2+) was predominantly achieved through the replacement reaction of BDE and EDTA-Cu.

  2. Enhanced Molecular Recognition between Nucleobases and Guanine-5'-monophosphate-disodium (GMP) by Surfactant Aggregates in Aqueous Solution.

    PubMed

    Liu, Zhang; Wang, Dong; Cao, Meiwen; Han, Yuchun; Xu, Hai; Wang, Yilin

    2015-07-15

    Only specific base pairs on DNA can bind with each other through hydrogen bonds, which is called the Watson-Crick (W/C) pairing rule. However, without the constraint of DNA chains, the nucleobases in bulk aqueous solution usually do not follow the W/C pairing rule anymore because of the strong competitive effect of water and the multi-interaction edges of nucleobases. The present work applied surfactant aggregates noncovalently functionalized by nucleotide to enhance the recognition between nucleobases without DNA chains in aqueous solution, and it revealed the effects of their self-assembling ability and morphologies on the recognition. The cationic ammonium monomeric, dimeric, and trimeric surfactants DTAB, 12-3-12, and 12-3-12-3-12 were chosen. The surfactants with guanine-5'-monophosphate-disodium (GMP) form micelles, vesicles, and fingerprint-like and plate-like aggregates bearing the hydrogen-bonding sites of GMP, respectively. The binding parameters of these aggregates with adenine (A), uracil (U), guanine (G), and cytosine(C) indicate that the surfactants can promote W/C recognitions in aqueous solution when they form vesicles (GMP/DTAB) or plate-like aggregates (GMP/12-3-12) with proper molecular packing compactness, which not only provide hydrophobic environments but also shield non-W/C recognition edges. However, the GMP/12-3-12 micelles with loose molecular packing, the GMP/12-3-12 fingerprint-like aggregates where the hydrogen bond sites of GMP are occupied by itself, and the GMP/12-3-12-3-12 vesicles with too strong self-assembling ability cannot promote W/C recognition. This work provides insight into how to design self-assemblies with the performance of enhanced molecule recognition.

  3. Disodium N,N-bis-(dithiocarboxy)ethanediamine: synthesis, performance, and mechanism of action toward trace ethylenediaminetetraacetic acid copper (II).

    PubMed

    Xiao, Xiao; Ye, Maoyou; Yan, Pingfang; Qiu, Yiqin; Sun, Shuiyu; Ren, Jie; Dai, Yongkang; Han, Dajian

    2016-10-01

    A new effective multi-dithiocarbamate heavy metal precipitant, disodium N,N-bis-(dithiocarboxy) ethanediamine (BDE), was synthesized by mixing ethanediamine with carbon disulfide under alkaline conditions, and it was utilized for removing trace ethylenediaminetetraacetic acid copper (II) (EDTA-Cu) from wastewater. Its structure was confirmed by ultraviolet spectra, Fourier transform infrared spectra, scanning electron microscopy, thermogravimetric analysis, and elemental analysis. The removal performance of EDTA-Cu by BDE was evaluated according to BDE dosage, initial concentration, pH, and reaction time through single-factor experiments. With the optimized conditions of a pH range of 3-9, dosage ratio of BDE/Cu of 1:1, PAM dosage of 1 mg/L, and reaction time of 4 min, the removal efficiency of Cu(2+) was more than 98 % from simulated wastewater containing EDTA-Cu with initial concentrations of 5-100 mg/L. Treatment of actual EDTA-Cu wastewater showed that BDE performed superior effectiveness, and the average residential concentration of Cu(2+) was 0.115 mg/L. Besides, the stability of chelated precipitate and the reaction mechanism of BDE and EDTA-Cu were also introduced. The toxicity characteristic leaching procedure (TCLP) and semi-dynamic leaching test (SDLT) indicated that the chelated precipitate was non-hazardous and stable in weak acid and alkaline conditions. The BDE reacts with EDTA-Cu at a stoichiometric ratio, and the removal of Cu(2+) was predominantly achieved through the replacement reaction of BDE and EDTA-Cu. PMID:27406222

  4. Influence of combined therapeutic potential of meso 2,3-dimercaptosuccinic acid and calcium disodium edetate on lead-induced testicular alterations in rats.

    PubMed

    Flora, G J; Arora, U; Seth, P K

    1999-12-01

    The therapeutic efficacy of a combination of meso 2,3-dimercaptosuccinic acid (DMSA) and calcium disodium EDTA in protecting testicular disorders in chronic lead intoxication was investigated. The results indicate that two five-days courses of the combined therapy produced a more effective recovery in the lead induced biochemical and histopathological disorders compared to conventional single 5 days therapy. No adverse effect of the chelators, when administered individually or in combination, was noticed in the testes of control (without lead exposure) animals.

  5. Effects of dietary pyrroloquinoline quinone disodium on growth, carcass characteristics, redox status, and mitochondria metabolism in broilers.

    PubMed

    Wang, J; Zhang, H J; Samuel, K G; Long, C; Wu, S G; Yue, H Y; Sun, L L; Qi, G H

    2015-02-01

    The potential benefits of supplementing pyrroloquinoline quinone disodium (PQQ·Na2) in the diet of broiler chicks were explored. We first examined the effect of different levels of dietary PQQ·Na2 on growth performance, carcass characteristics, and plasma biochemical parameters (trial 1). A total of 490 1-day-old male Arbor Acres (AA) broiler chicks were randomly divided into 5 dietary groups supplemented with 0, 0.05, 0.1, 0.2, or 0.4 mg PQQ·Na2/kg feed. As the 0.2 mg/kg PQQ·Na2 supplement gave the best performance, we then investigated whether this level of PQQ·Na2 influenced the redox status of plasma samples and mitochondrial-related metabolism (trial 2). A total of 120 1-day-old male AA chicks were randomly divided into 2 groups supplemented with 0 or 0.2 mg PQQ·Na2/kg diet. In trial 1, birds fed a diet containing 0.2 mg PQQ·Na2/kg showed lower feed conversion ratio compared with those fed the control diet in the overall study (d 1 to 42, P=0.039). Breast muscle yield (d 42) increased quadratically in response to dietary PQQ·Na2 supplementation (P=0.021). Analysis of plasma biochemical parameters revealed that feeding broiler chicks with ≤0.4 mg/kg PQQ·Na2 did not cause adverse health effects. In trial 2, birds fed 0.2 mg/kg PQQ·Na2 again showed improved feed efficiency than the control birds in the grower and overall phases (P=0.038 and 0.016, respectively). In addition, dietary PQQ·Na2 supplementation resulted in a higher anti-oxidative capacity (P=0.001), lower redox potential (P=0.008), and higher hepatic citrate synthase activity (P=0.002). In contrast, no difference in hepatic mitochondrial DNA copy number was observed between the 2 experimental groups (P>0.1). These results indicate that PQQ·Na2 is a potentially effective feed additive for improving feed efficiency, stimulating breast muscle development, and maintaining redox status in broiler chicks. Enhancement of mitochondria efficiency, rather than modulating mitochondria numbers

  6. Pharmacokinetics of disodium fosfomycin in broilers and dose strategies to comply with its pharmacodynamics versus Escherichia coli.

    PubMed

    Gutierrez, L; Ocampo, L; Rosario, C; Sumano, H

    2010-10-01

    The objective of this study was to determine, in broilers, which modality of disodium fosfomycin (DF) administration and at what dose the best pharmacokinetic (PK) profile could be obtained, taking as reference a 110 field bacterial strains of Escherichia coli minimum inhibitory concentration survey. The DF was administered via drinking water either ad libitum or at a higher concentration having 1 h of water restriction to build up thirst in the birds (loading dose). Dosages tested were 10, 20, 40, and 80 mg/kg per administration, either once or twice daily. Birds included were 24-d-old Cornish broilers randomly assigned to 16 groups of 200 birds per group and 3 replicates per group. The PK of DF was determined after ad libitum administration of either a single- or double-loading dose or after an initial loading dose followed by ad libitum medication. Also, PK after i.v. administration was studied in separate groups. Serial blood samplings were performed in all groups. Serum obtained was analyzed for DF and a possible active metabolite by means of a microbiological agar diffusion assay. The DF showed a short elimination half-life (approximately 2 h after oral loading administration) with a rapid clearance (1.23 to 1.42 mL/kg per h). Apparent volume of distribution-area under the curve values were also low (10 and 80 mg/kg=0.25 L/kg and 0.22 L/kg, respectively). Considering a minimum inhibitory concentration level that inhibited 90% of total strains of 8 µg/mL for E. coli, it is concluded that single-loading administration at 10, 20, 40, and 80 mg/kg complies poorly with sustained serum concentrations over a dosing interval of 24 h. Doses of 10 and 20 mg/kg twice a day also were insufficient to attain therapeutic concentrations. Useful serum concentrations of DF to treat outbreaks of susceptible E. coli require an initial loading dose of 40 mg/kg, followed by an ad libitum medication of 40 mg/kg 8 h later (80 mg/kg per d).

  7. Passive cutaneous anaphylaxis in the rat, induced with two homologous reagin-like antibodies, and its specific inhibition with disodium cromoglycate

    PubMed Central

    Goose, J.; Blair, A. M. J. N.

    1969-01-01

    Rats immunized with egg albumin and Bordetella pertussis organisms produce a `mast cell sensitizing' antibody (MCSAb) which is thermolabile, a potent skin sensitizer and reagin in character. Similarly the immune response to Nippostrongylus brasiliensis in rats is closely associated with the formation of antibodies which also resembles human reagins. Homologous passive cutaneous anaphylactic (PCA) reactions induced by N. brasiliensis serum were found to be similar to those produced using the adjuvant induced antibody in that both were completely inhibited by, combined treatment with mepyramine and 2-bromo-D-lysergic acid diethylamide (BOL148), cyproheptadine or pretreatment with compound 48/80. In contrast, skin reactions involving passive sensitization of rats with rabbit hyperimmune antiserum were much less affected. Studies on mast cell disruption at the site of PCA reactions showed that such reactions using N. brasiliensis serum were accompanied by degranulation of mast cells, and confirmed that mast cell damage occurs in PCA induced with MCSAb. Both the PCA and the mast cell disruption were maximal 5 minutes after antigen challenge in both rat reagin systems. The skin reaction produced using rabbit hyperimmune antiserum was not primarily dependent on, or associated with, mast cell disruption, since it was still possible to induce skin reactions when the mast cells had been disrupted by compound 48/80, and skin reactions could be obtained without significant mast cell disruption. Disodium cromoglycate, a new compound introduced for the treatment of asthma, was shown to inhibit both the PCA and mast cell disruption induced using both rat reagin antibodies but not the skin reactions produced with rabbit anti-serum. It was possible to obtain substantial inhibition of mast cell disruption induced by rat reagin, even when the PCA was inhibited only slightly. At higher doses the discharge of the mediators from mast cells was also prevented. This interference with mast

  8. Effects of disodium fumarate on ruminal fermentation and microbial communities in sheep fed on high-forage diets.

    PubMed

    Zhou, Y W; McSweeney, C S; Wang, J K; Liu, J X

    2012-05-01

    This study was conducted to investigate effects of disodium fumarate (DF) on fermentation characteristics and microbial populations in the rumen of Hu sheep fed on high-forage diets. Two complementary feeding trials were conducted. In Trial 1, six Hu sheep fitted with ruminal cannulae were randomly allocated to a 2 × 2 cross-over design involving dietary treatments of either 0 or 20 g DF daily. Total DNA was extracted from the fluid- and solid-associated rumen microbes, respectively. Numbers of 16S rDNA gene copies associated with rumen methanogens and bacteria, and 18S rDNA gene copies associated with rumen protozoa and fungi were measured using real-time PCR, and expressed as proportion of total rumen bacteria 16S rDNA. Ruminal pH decreased in the DF group compared with the control (P < 0.05). Total volatile fatty acids increased (P < 0.001), but butyrate decreased (P < 0.01). Addition of DF inhibited the growth of methanogens, protozoa, fungi and Ruminococcus flavefaciens in fluid samples. Both Ruminococcus albus and Butyrivibrio fibrisolvens populations increased (P < 0.001) in particle-associated samples. Trial 2 was conducted to investigate the adaptive response of rumen microbes to DF. Three cannulated sheep were fed on basal diet for 2 weeks and continuously for 4 weeks with supplementation of DF at a level of 20 g/day. Ruminal samples were collected every week to analyze fermentation parameters and microbial populations. No effects of DF were observed on pH, acetate and butyrate (P > 0.05). Populations of methanogens and R. flavefaciens decreased in the fluid samples (P < 0.001), whereas addition of DF stimulated the population of solid-associated Fibrobacter succinogenes. Population of R. albus increased in the 2nd to 4th week in fluid-associated samples and was threefold higher in the 4th week than control week in solid samples. Analysis of denaturing gradient gel electrophoresis fingerprints revealed that there were significant changes in rumen

  9. Effects of disodium fumarate on ruminal fermentation and microbial communities in sheep fed on high-forage diets.

    PubMed

    Zhou, Y W; McSweeney, C S; Wang, J K; Liu, J X

    2012-05-01

    This study was conducted to investigate effects of disodium fumarate (DF) on fermentation characteristics and microbial populations in the rumen of Hu sheep fed on high-forage diets. Two complementary feeding trials were conducted. In Trial 1, six Hu sheep fitted with ruminal cannulae were randomly allocated to a 2 × 2 cross-over design involving dietary treatments of either 0 or 20 g DF daily. Total DNA was extracted from the fluid- and solid-associated rumen microbes, respectively. Numbers of 16S rDNA gene copies associated with rumen methanogens and bacteria, and 18S rDNA gene copies associated with rumen protozoa and fungi were measured using real-time PCR, and expressed as proportion of total rumen bacteria 16S rDNA. Ruminal pH decreased in the DF group compared with the control (P < 0.05). Total volatile fatty acids increased (P < 0.001), but butyrate decreased (P < 0.01). Addition of DF inhibited the growth of methanogens, protozoa, fungi and Ruminococcus flavefaciens in fluid samples. Both Ruminococcus albus and Butyrivibrio fibrisolvens populations increased (P < 0.001) in particle-associated samples. Trial 2 was conducted to investigate the adaptive response of rumen microbes to DF. Three cannulated sheep were fed on basal diet for 2 weeks and continuously for 4 weeks with supplementation of DF at a level of 20 g/day. Ruminal samples were collected every week to analyze fermentation parameters and microbial populations. No effects of DF were observed on pH, acetate and butyrate (P > 0.05). Populations of methanogens and R. flavefaciens decreased in the fluid samples (P < 0.001), whereas addition of DF stimulated the population of solid-associated Fibrobacter succinogenes. Population of R. albus increased in the 2nd to 4th week in fluid-associated samples and was threefold higher in the 4th week than control week in solid samples. Analysis of denaturing gradient gel electrophoresis fingerprints revealed that there were significant changes in rumen

  10. Determination of calcium disodium ethylenediaminetetraacetate (E385) in marketed bottled legumes, artichokes and emulsified sauces by gas chromatography with mass spectrometric detection.

    PubMed

    Jiménez, Juan J

    2014-01-01

    An original method to determine the food additive calcium disodium ethylenediaminetetraacetate in bottled food is proposed. The method involves the solid-liquid extraction of a portion of the whole content of legume or artichoke bottles, or the dilution of sauce samples, with water followed by an evaporation step by heating. Finally, ethylenediaminetetraacetic acid is methylated and determined by GC. Recoveries obtained on spiked samples were acceptable (96-108%) with RSDs comprised from 4.3% to 10%. Results suggest that the determination of additive only in the liquid phase of legume or artichoke bottles is not suitable to know its total amount because the additive is distributed between the liquid and solid phases. The contribution of each step of the analytical method to the uncertainty of the measured concentration has been assessed by a "bottom-up" approach, including the heterogeneity of the sample which resulted to be very variable after studying twenty samples. PMID:24444909

  11. Determination of calcium disodium ethylenediaminetetraacetate (E385) in marketed bottled legumes, artichokes and emulsified sauces by gas chromatography with mass spectrometric detection.

    PubMed

    Jiménez, Juan J

    2014-01-01

    An original method to determine the food additive calcium disodium ethylenediaminetetraacetate in bottled food is proposed. The method involves the solid-liquid extraction of a portion of the whole content of legume or artichoke bottles, or the dilution of sauce samples, with water followed by an evaporation step by heating. Finally, ethylenediaminetetraacetic acid is methylated and determined by GC. Recoveries obtained on spiked samples were acceptable (96-108%) with RSDs comprised from 4.3% to 10%. Results suggest that the determination of additive only in the liquid phase of legume or artichoke bottles is not suitable to know its total amount because the additive is distributed between the liquid and solid phases. The contribution of each step of the analytical method to the uncertainty of the measured concentration has been assessed by a "bottom-up" approach, including the heterogeneity of the sample which resulted to be very variable after studying twenty samples.

  12. [Perspectives of disodium salt 2.4-di(1-metoxyethyl)-deuteroporphyrin - IX ("Dimegin") application for photodynamic therapy in non-oncologic cases].

    PubMed

    Bondarenko, V M; Alekseev, Iu V; Mislavskiĭ, O V; Ponomarev, G V

    2014-01-01

    Effects of disodium salt 2,4-di(1-metoxyethyl)-deuteroporphyrine-IX (Dimegin) and the light from Soret band (»395-405 nm) at the viability of microbial cells and at their potential to form microbial biofilms have been compared with traditional antiseptics. Irradiation of microbial cells of S. aureus, E. coli, C. albicans and others with diode light (power density 0.05 Wt/cm2) caused a bactericidial effect similar to that obtained with standard anticeptics (chlorhexidine and dioxidine). A comparative study of the effectiveness of Dimegin and Photoditazine (a soluble salt of chlorine e6) as photosensitizers have been performed using the test system of erythrocyte hemolysis in vitro under irradiation with light from the Sore band. Results have shown insignificant difference in the photodynamic effect with similar doses of absorbed light and preparation concentration. PMID:25019396

  13. The beneficial effects of 18β-glycyrrhetinic acid following oxidative and neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion in a C57BL/J6 mouse model.

    PubMed

    Oztanir, M Namik; Ciftci, Osman; Cetin, Aslı; Durak, M Akif; Basak, Nese; Akyuva, Yener

    2014-08-01

    This study investigated the effects of 18β-glycyrrhetinic acid (GA) on neuronal damage in brain tissue caused by global cerebral ischemia/reperfusion (I/R) in C57BL/J6 mice. All subjects (n = 40) were equally divided into four groups: (1) sham-operated (SH), (2) I/R, (3) GA, and (4) GA+I/R. The SH group was used as a control. In the I/R group, the bilateral carotid arteries were clipped for 15 min, and the mice were treated with the vehicle for 10 days. In the GA group, mice were given GA (100 mg/kg) for 10 days following a median incision without carotid occlusion. In the GA+I/R group, the I/R model was applied to the mice exactly as in the I/R group, and they were then treated with the same dose of GA for 10 days. Cerebral I/R significantly induced oxidative stress via an increase in lipid peroxidaitons and a decrease in elements of the antioxidant defense systems. However, GA treatment was protective against the oxidative effects of I/R by inducing significant increases in antioxidant defense systems and a significant decrease of lipid peroxidations. Additionally, cerebral I/R increased the incidence of histopathological damage and apoptosis in brain tissue, but these neurodegenerative effects were eliminated by GA treatment. Therefore, the current study demonstrated that GA treatment effectively prevents oxidative and histological damage in the brain caused by global I/R. In this context, GA may be useful for the attenuation of the negative effects of global cerebral I/R and, in the future, it may be a viable and safe alternative treatment for ischemic stroke in humans.

  14. Photodynamic therapy of human skin tumors using topical application of 5-aminolevulinic acid, dimethylsulfoxide (DMSO), and edetic acid disodium salt (EDTA)

    NASA Astrophysics Data System (ADS)

    Orenstein, Arie; Kostenich, Gennady; Tsur, H.; Roitman, Leonid; Ehrenberg, Benjamin; Malik, Zvi

    1995-01-01

    The results of photodynamic therapy (PDT) in 48 patients bearing basal cell carcinoma (BCC) and 7 patients with squamous cell carcinoma (SCC) of the skin are described. Five- aminolevulinic acid (5-ALA) was applied topically in two formulations. The first formulation contained 20% of 5-ALA in a base cream, and the second formulation (5-ALA composite cream), contained an additional 2% of dimethylsulfoxide (DMSO) and 2% of edetic acid disodium salt (EDTA). The creams were left on the skin for 2 - 5 hours. Production of protoporphyrin (PP) was measured in situ by a laser-induced fluorescence (LIF) method. The results of fluorescence measurement clearly indicate that PP accumulation in tumors induced by the 5-ALA composite cream was markedly higher than that induced by the 5-ALA cream. The tumors were light-irradiated (600 - 720 nm) after 4 - 5 hours of cream applications, using the light delivery system Versa-Light by a light dose of 100 J/cm2. The clinically superficial BCC tumors were highly responsive to PDT; the overall result in BCC patients was an 85.4% complete response. Histological examination showed an initial edematous reaction, followed by necrosis and complete disappearance of the tumor. The superficial SCC tumors showed a 100% complete response after PDT. The ulcerated nodular SCC showed partial responses.

  15. Characterization of interactions between methoxatin disodium salt and human serum albumin by pressure-assisted capillary electrophoresis/frontal analysis and circular dichroism spectroscopy.

    PubMed

    Zhao, Lijuan; Chen, Dongying

    2015-01-01

    Pressure-assisted capillary electrophoresis (PACE)/frontal analysis (FA) and circular dichroism spectroscopy were utilized to investigate the interactions between methoxatin disodium salt (PQQ-2Na) and human serum albumin (HSA). With the PACE/FA method, sodium phosphate buffer solution (67 mm, pH 7.4) was used as the background electrolyte. Hydrodynamic injection at 50 mbar for 50 s and external pressure of 50 mbar were applied. The binding constant and the number of primary binding sites to HSA were obtained under fixed concentration of PQQ-2Na (100 µm) and increasing HSA concentration (0~475 µm). The thermodynamic parameters characterized the main acting forces of hydrophobic and electrostatic interactions. The displacement experiments using phenylbutazone and flurbiprofen as ligand markers suggested that the binding site was the Sudlow site I of the HSA molecule. Circular dichroism spectroscopy was further employed to evaluate the conformation changes of HSA under the interaction of PQQ-2Na. This work provides comprehensive information for understanding the interactions between PQQ-2Na and HSA.

  16. A liquid chromatography-fluorimetric method for the in vitro estimation of the skin penetration of disodium phenyldibenzimidazole tetrasulfonate from sunscreen formulations through human skin.

    PubMed

    Balaguer, A; Salvador, A; Chisvert, A; Meliá, M; Herráez, M; Díez, O

    2006-08-01

    Disodium phenyldibenzimidazole tetrasulfonate (PDT) is a new organic UV filter with hydrophilic properties used in modern sunscreen spray formulations. The aim of this work was to develop and validate an analytical method that can be used to study skin absorption of PDT from sunscreens. Results obtained in vitro for human skin showed a low level of absorption. The proposed in vitro method employs a diffusion cell. Sunscreen lotion was applied onto pretreated human skin, which was then placed in the cell. PDT was collected in a receptor liquid, the surface of which was in contact with the skin. The solutions obtained were diluted appropriately and analyzed by liquid chromatography without any interference. The analytical features of chromatographic determination with fluorimetic detection were suited to this analytical problem, since this method gave a limit of detection of 1 ng ml(-1). Phenol red (PR) was used as a marker to check the skin integrity, and a sensitive method based on sequential injection on-line solid-phase extraction coupled with spectrophotometric detection was developed for determining this marker in the receptor liquid in order to screen the cells.

  17. Permeation and metabolism of a novel ascorbic acid derivative, disodium isostearyl 2-O-L-ascorbyl phosphate, in human living skin equivalent models.

    PubMed

    Shibayama, H; Hisama, M; Matsuda, S; Ohtsuki, M

    2008-01-01

    A novel amphiphilic vitamin C (VC) derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na), which possesses a C(18) alkyl chain attached to a stable ascorbate derivative, sodium L-ascorbic acid 2-phosphate (VCP-Na), was evaluated as a topical prodrug of VC with transdermal activity in human living skin equivalent (LSE) models. The permeation assay used was EPI-606X in the Franz-type diffusion cell system. VCP-IS-2Na exhibited much better permeability than VC and VCP-Na. The accumulation assays applied were EPI-200X and LSE-high by the dynamic system. The increased skin accumulation of VCP-IS-2Na was superior to that of VCP-Na and VC. VCP-IS-2Na that is susceptible to enzymatic hydrolysis by esterase and/or phosphatase released VC in the skin. Measurement of the metabolites that permeated and accumulated from the skin model suggested that VCP-IS-2Na was mainly metabolized via VCP-Na to VC in EPI-606X and EPI-200X, while it was mainly metabolized directly to VC in TESTSKIN LSE-high. Thus, these characteristics indicate that the novel VC derivative, VCP-IS-2Na, may be advantageous as a readily available source of VC for skin care applications.

  18. The Ability of PAS, Acetylsalicylic Acid and Calcium Disodium EDTA to Protect Against the Toxic Effects of Manganese on Mitochondrial Respiration in Gill of Crassostrea virginica.

    PubMed

    Crawford, Sherine; Davis, Kiyya; Saddler, Claudette; Joseph, Jevaun; Catapane, Edward J; Carroll, Margaret A

    2011-01-01

    Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, a condition similar to Parkinson's disease. Previously we showed that Mn had a neurotoxic effect on the dopaminergic, but not serotonergic, innervation of the lateral ciliated cells in the gill of the Eastern Oyster, Crassostrea virginica. While the mechanism of action of Mn toxicity is not completely understood, studies suggest that Mn toxicity may involve mitochondrial damage and resulting neural dysfunction in the brain's dopaminergic system. In this study we utilized micro-batch chambers and oxygen probes to measure oyster gill mitochondrial respiration in the presence of Mn and potential Mn blockers. The addition of Mn to respiring mitochondria caused a dose dependent decrease in mitochondrial O(2) consumption. Pretreating mitochondria with calcium disodium EDTA (caEDTA), p aminosalicylic acid (PAS) or acetylsalicylic acid (ASA) before Mn additions, provided full protection against the toxic effects of Mn. While mitochondrial pretreatment with any of the 3 drugs effectively blocked Mn toxicity, none of the drugs tested was able to reverse the decrease in mitochondrial O(2) consumption seen in Mn treated mitochondria. The study found that high levels of Mn had a toxic effect on gill mitochondrial O(2) consumption and that this effect could be blocked by the drugs caEDTA, PAS and ASA. C. virginica continues to be a good model with which to investigate the mechanism that underlies manganese neurotoxcity and in the pharmacological study of drugs to treat or prevent Manganism. PMID:21977482

  19. The Ability of PAS, Acetylsalicylic Acid and Calcium Disodium EDTA to Protect Against the Toxic Effects of Manganese on Mitochondrial Respiration in Gill of Crassostrea virginica

    PubMed Central

    Crawford, Sherine; Davis, Kiyya; Saddler, Claudette; Joseph, Jevaun; Catapane, Edward J.; Carroll, Margaret A.

    2011-01-01

    Manganese (Mn) is an essential metal that at excessive levels in brain causes Manganism, a condition similar to Parkinson's disease. Previously we showed that Mn had a neurotoxic effect on the dopaminergic, but not serotonergic, innervation of the lateral ciliated cells in the gill of the Eastern Oyster, Crassostrea virginica. While the mechanism of action of Mn toxicity is not completely understood, studies suggest that Mn toxicity may involve mitochondrial damage and resulting neural dysfunction in the brain’s dopaminergic system. In this study we utilized micro-batch chambers and oxygen probes to measure oyster gill mitochondrial respiration in the presence of Mn and potential Mn blockers. The addition of Mn to respiring mitochondria caused a dose dependent decrease in mitochondrial O2 consumption. Pretreating mitochondria with calcium disodium EDTA (caEDTA), p aminosalicylic acid (PAS) or acetylsalicylic acid (ASA) before Mn additions, provided full protection against the toxic effects of Mn. While mitochondrial pretreatment with any of the 3 drugs effectively blocked Mn toxicity, none of the drugs tested was able to reverse the decrease in mitochondrial O2 consumption seen in Mn treated mitochondria. The study found that high levels of Mn had a toxic effect on gill mitochondrial O2 consumption and that this effect could be blocked by the drugs caEDTA, PAS and ASA. C. virginica continues to be a good model with which to investigate the mechanism that underlies manganese neurotoxcity and in the pharmacological study of drugs to treat or prevent Manganism. PMID:21977482

  20. In vivo percutaneous absorption of boric acid, borax, and disodium octaborate tetrahydrate in humans compared to in vitro absorption in human skin from infinite and finite doses.

    PubMed

    Wester, R C; Hui, X; Hartway, T; Maibach, H I; Bell, K; Schell, M J; Northington, D J; Strong, P; Culver, B D

    1998-09-01

    Literature from the first half of this century report concern for toxicity from topical use of boric acid, but assessment of percutaneous absorption has been impaired by lack of analytical sensitivity. Analytical methods in this study included inductively coupled plasma-mass spectrometry which now allows quantitation of percutaneous absorption of 10B in 10B-enriched boric acid, borax, and disodium octaborate tetrahydrate (DOT) in biological matrices. This made it possible, in the presence of comparatively large natural dietary boron intakes for the in vivo segment of this study, to quantify the boron passing through skin. Human volunteers were dosed with 10B-enriched boric acid, 5.0%, borax, 5.0%, or disodium octaborate tetrahydrate, 10%, in aqueous solutions. Urinalysis, for boron and changes in boron isotope ratios, was used to measure absorption. Boric acid in vivo percutaneous absorption was 0.226 (SD = 0.125) mean percentage dose, with flux and permeability constant (Kp) calculated at 0.009 microgram/cm2/h and 1.9 x 10(-7) cm/h, respectively. Borax absorption was 0.210 (SD = 0.194) mean percentage of dose, with flux and Kp calculated at 0.009 microgram/cm2/h and 1.8 x 10(-7) cm/h, respectively. DOT absorption was 0.122 (SD = 0.108) mean percentage, with flux and Kp calculated at 0.01 microgram/cm2/h and 1.0 x 10(-7) cm/h, respectively. Pretreatment with the potential skin irritant 2% sodium lauryl sulfate had no effect on boron skin absorption. In vitro human skin percentage of doses of boric acid absorbed were 1.2 for a 0.05% solution, 0.28 for a 0.5% solution, and 0.70 for a 5.0% solution. These absorption amounts translated into flux values of, respectively, 0.25, 0.58, and 14.58 micrograms/cm2/h and permeability constants (Kp) of 5.0 x 10(-4), 1.2 x 10(-4), and 2.9 x 10(-4) cm/h for the 0.05, 0.5, and 5.0% solutions. The above in vitro doses were at infinite, 1000 microliters/cm2 volume. At 2 microliters/cm2 (the in vivo dosing volume), flux decreased some

  1. Effect of disodium cromoglycate (DSCG) and antihistamines on post-irradiation cerebral blood flow and plasma levels of histamine and neurotensin

    SciTech Connect

    Cockerham, L.G.; Pautler, E.L.; Carraway, R.E.; Cochrane, D.E.; Hampton, J.D.

    1988-01-01

    In an attempt to elucidate mechanisms underlying the irradiation-induced decrease in regional cerebral blood flow (rCBF) in primates, hippocampal and visual cortical blood flows of rhesus monkeys were measured by hydrogen clearance, before and after exposure to 100-Gy, whole-body, gamma irradiation. Systemic blood pressures were monitored simultaneously. Systemic arterial plasma histamine and neurotensin levels were determined preirradiation and postirradiation. Compared to control animals, the irradiated monkeys exhibited an abrupt decline in systemic blood pressure to 23% of the preirradiation level within 10-min postirradiation, falling to 12% by 60 min. A decrease in hippocampal blood flow to 32% of the preirradiation level was noted at 10-min postirradiation, followed by a slight recovery to 43% at 30 min and a decline to 23% by 60 min. The cortical blood flow for the same animals showed a steady decrease to 29% of the preirradiation levels by 60-min postirradiation. Animals given the mast-cell stabilizer disodium cromoglycate and the antihistamines mepyramine and cimetidine before irradiation did not exhibit an abrupt decline in blood pressure but displayed a gradual decrease to a level 33% below preirradiation levels by 60 min postirradiation. Also, the treated, irradiated monkeys displayed rCBF values that were not significantly different from the nonirradiated controls. The plasma neurotensin levels in the irradiated animals, treated and untreated, indicated a nonsignificant postirradiation increase above control levels.

  2. Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation.

    PubMed

    Kumar, Neeraj; Soni, Sandeep; Singh, Thakuri; Kumar, Amit; Ahmad, Farhan Jalees; Bhatnagar, Aseem; Mittal, Gaurav

    2015-12-01

    Medical management of heavy metal toxicity, including radioactive ones, is a cause for concern because of their increased use in energy production, healthcare, and mining. Though chelating agents like EDTA and DTPA in parenteral form are available, no suitable oral formulation is there that can trap ingested heavy metal toxicants in the stomach itself, preventing their systemic absorption. The objective of the present study was to develop and optimize gastro-retentive controlled-release tablets of calcium-disodium edentate (Ca-Na2EDTA). Gastro-retentive tablet of Ca-Na2EDTA was prepared by direct compression method. Thirteen tablet formulations were designed using HPMC-K4M, sodium chloride, and carbopol-934 along with effervescing agents sodium bicarbonate and citric acid. Tablet swelling ability, in vitro buoyancy, and drug dissolution studies were conducted in 0.1 N HCl at 37 ± 0.5°C. Ca-Na2EDTA was radiolabeled with technetium-99m for scintigraphy-based in vivo evaluation. Formula F8 (Ca-Na2EDTA 200 mg, carbopol 100 mg, avicel 55 mg, citric acid 30 mg, NaHCO3 70 mg, NaCl 100 mg, and HPMC 95 mg) was found to be optimum in terms of excellent floating properties and sustained drug release. F8 fitted best for Korsmeyer-Peppas equation with an R (2) value of 0.993. Gamma scintigraphy in humans showed mean gastric retention period of 6 h. Stability studies carried out in accordance with ICH guidelines and analyzed at time intervals of 0, 1, 2, 4, and 6 months have indicated insignificant difference in tablet hardness, drug content, total floating duration, or matrix integrity of the optimized formulation. Gastro-retentive, controlled-release tablet of Ca-Na2EDTA was successfully developed using effervescent technique as a potential oral antidote for neutralizing ingested heavy metal toxicity. PMID:25771737

  3. Long-term betamethasone 21-phosphate disodium treatment has distinct effects in CD1 and DBA/2 mice on animal behavior accompanied by opposite effects on neurogenesis.

    PubMed

    Aiello, Rossana; Crupi, Rosalia; Leo, Antonio; Chimirri, Serafina; Rispoli, Vincenzo; Marra, Rosario; Citraro, Rita; Cuzzocrea, Salvatore; De Sarro, Giovambattista; Russo, Emilio

    2015-02-01

    One of the most peculiar characteristics of the stress response is the pronounced inter-individual and inter-strain variability both in behavioral and neurochemical outcomes. Several studies confirm that rodents belonging to the same or different strain and/or gender, when exposed to a stressor, may show behavioral and cognitive differences. We compared the effects of long-term betamethasone 21-phosphate disodium (BTM), a widely clinically used corticosteroid, on animal behavior and neurogenesis in CD1 and DBA/2 mice. BTM treatment, in CD1 mice, increased body weight gain and anxiety parameters while having pro-depressant effects. Furthermore, BTM significantly reduced neurogenesis in the dentate gyrus of the hippocampus. Finally, BTM treatment induced a significant impairment in memory and learning performance in the Morris water maze. At odds, BTM administration, in DBA/2 mice, caused a significant reduction in the body weight while not modifying anxiety parameters. In addition, both an increased synaptogenesis and neurogenesis were found. Similarly to CD1 mice, also in DBA/2 mice, memory and learning were impaired. Our data confirm that long-term exposure to corticosteroids can generate or aggravate psychiatric/neurologic disorders such as depression, anxiety, memory and learning. Our study did not reveal significant differences between corticosterone and BTM treatment in CD1 mice. In contrast, BTM treatment in mice with an anxious phenotype (DBA/2 mice) revealed some contrasting results indicating that genetic factors can influence corticosteroids dependent effects. Finally, our data further underline the need for a re-evaluation of neurogenesis role; the increased neurogenesis observed in DBA/2 mice and behavioral effects might be distinguished phenomena.

  4. [Thallium-201 myocardial scintigraphy after intravenous infusion of adenosine triphosphate disodium: a preliminary study in the diagnosis of coronary artery disease].

    PubMed

    Kinoshita, S; Yamashita, S; Suzuki, T; Muramatsu, T; Ide, M; Dohi, Y; Nishimura, K; Miyamae, T

    1991-12-01

    The feasibility and safety of thallium-201 myocardial scintigraphy after the intravenous infusion of adenosine triphosphate disodium (ATP) (Adetphos, Kowa) were studied in eight patients with angina pectoris and/or old myocardial infarction. Coronary arteriography (CAG) was performed by the conventional method in all patients. ATP was infused for 5 min and thallium was injected at 3 min after the start of ATP infusion. ATP was given at 0.12 mg/min/kg in two patients (group A), 0.16 mg/min/kg in three patients (group B), 0.20 mg/min/kg in one patient (group C) and 0.28 mg/min/kg in two patients (group D). SPECT images were obtained at 10 min and 180 min after thallium injection. No significant hemodynamic changes were observed in group A and B. Severe hypotension was observed in group C and one member of group D. Chest pain was experienced by one patient in group A, two in group B, one in group C, and both of the two in group D. ST depression on the electrocardiogram (ECG) was documented in one patient each of groups B and C. In one group D patient, the study was discontinued because of complete atrioventricular block persistent for 5 beats. The correlation between thallium imaging and CAG was unclear in group A, reasonable in groups B and C, and obscure in group D because of side effects. None of the patients who developed side effects of ATP were administered sublingual nitroglycerin or intravenous aminophylline. Their symptoms or ECG changes improved spontaneously within 2 min and disappeared within 5 min after termination of infusion. In conclusion, the optimal ATP regimen for this purpose was considered to be a 5 min infusion at 0.16 mg/kg/min and this method was found to be feasible and safe. PMID:1784093

  5. Development and Optimization of Gastro-Retentive Controlled-Release Tablet of Calcium-Disodium Edentate and its In Vivo Gamma Scintigraphic Evaluation.

    PubMed

    Kumar, Neeraj; Soni, Sandeep; Singh, Thakuri; Kumar, Amit; Ahmad, Farhan Jalees; Bhatnagar, Aseem; Mittal, Gaurav

    2015-12-01

    Medical management of heavy metal toxicity, including radioactive ones, is a cause for concern because of their increased use in energy production, healthcare, and mining. Though chelating agents like EDTA and DTPA in parenteral form are available, no suitable oral formulation is there that can trap ingested heavy metal toxicants in the stomach itself, preventing their systemic absorption. The objective of the present study was to develop and optimize gastro-retentive controlled-release tablets of calcium-disodium edentate (Ca-Na2EDTA). Gastro-retentive tablet of Ca-Na2EDTA was prepared by direct compression method. Thirteen tablet formulations were designed using HPMC-K4M, sodium chloride, and carbopol-934 along with effervescing agents sodium bicarbonate and citric acid. Tablet swelling ability, in vitro buoyancy, and drug dissolution studies were conducted in 0.1 N HCl at 37 ± 0.5°C. Ca-Na2EDTA was radiolabeled with technetium-99m for scintigraphy-based in vivo evaluation. Formula F8 (Ca-Na2EDTA 200 mg, carbopol 100 mg, avicel 55 mg, citric acid 30 mg, NaHCO3 70 mg, NaCl 100 mg, and HPMC 95 mg) was found to be optimum in terms of excellent floating properties and sustained drug release. F8 fitted best for Korsmeyer-Peppas equation with an R (2) value of 0.993. Gamma scintigraphy in humans showed mean gastric retention period of 6 h. Stability studies carried out in accordance with ICH guidelines and analyzed at time intervals of 0, 1, 2, 4, and 6 months have indicated insignificant difference in tablet hardness, drug content, total floating duration, or matrix integrity of the optimized formulation. Gastro-retentive, controlled-release tablet of Ca-Na2EDTA was successfully developed using effervescent technique as a potential oral antidote for neutralizing ingested heavy metal toxicity.

  6. Dietary supplementation of pyrroloquinoline quinone disodium protects against oxidative stress and liver damage in laying hens fed an oxidized sunflower oil-added diet.

    PubMed

    Wang, J; Zhang, H J; Xu, L; Long, C; Samuel, K G; Yue, H Y; Sun, L L; Wu, S G; Qi, G H

    2016-07-01

    The protective effects of dietary pyrroloquinoline quinone disodium (PQQ.Na2) supplementation against oxidized sunflower oil-induced oxidative stress and liver injury in laying hens were examined. Three hundred and sixty 53-week-old Hy-Line Gray laying hens were randomly allocated into one of the five dietary treatments. The treatments included: (1) a diet containing 2% fresh sunflower oil; (2) a diet containing 2% thermally oxidized sunflower oil; (3) an oxidized sunflower oil diet with 100 mg/kg of added vitamin E; (4) an oxidized sunflower oil diet with 0.08 mg/kg of PQQ.Na2; and (5) an oxidized sunflower oil diet with 0.12 mg/kg of PQQ.Na2. Birds fed the oxidized sunflower oil diet showed a lower feed intake compared to birds fed the fresh oil diet or oxidized oil diet supplemented with vitamin E (P=0.009). Exposure to oxidized sunflower oil increased plasma malondialdehyde (P<0.001), hepatic reactive oxygen species (P<0.05) and carbonyl group levels (P<0.001), but decreased plasma glutathione levels (P=0.006) in laying hens. These unfavorable changes induced by the oxidized sunflower oil diet were modulated by dietary vitamin E or PQQ.Na2 supplementation to levels comparable to the fresh oil group. Dietary supplementation with PQQ.Na2 or vitamin E increased the activities of total superoxide dismutase and glutathione peroxidase in plasma and the liver, when compared with the oxidized sunflower oil group (P<0.05). PQQ.Na2 or vitamin E diminished the oxidized sunflower oil diet induced elevation of liver weight (P=0.026), liver to BW ratio (P=0.001) and plasma activities of alanine aminotransferase (P=0.001) and aspartate aminotransferase (P<0.001) and maintained these indices at the similar levels to the fresh oil diet. Furthermore, oxidized sunflower oil increased hepatic DNA tail length (P<0.05) and tail moment (P<0.05) compared with the fresh oil group. Dietary supplementation of PQQ.Na2 or vitamin E decreased the oxidized oil diet induced DNA tail length

  7. Evaluation of the internal thoracic arterial graft patency by the transthoracic Doppler method under continuous intravenous infusion of adenosine triphosphate disodium.

    PubMed

    Fukata, Y; Horike, K; Fujimoto, E; Shimoe, Y; Kanbara, T

    1999-10-01

    Usefulness of the Doppler method under continuous infusion of adenosine triphosphate disodium (ATP) for improvement of accuracy in the diagnosis of the left internal thoracic arterial graft (LITA) patency was examined using transthoracic ultrasonic echocardiography. 1) Influence of ATP on the Doppler velocity in a graft was examined in 7 patients with good LITA grafts using physiological saline as the control. In the ATP group, 80 mg of ATP was dissolved in 20 ml physiological saline and continuously infused at 0.14 mg/kg/min. In the saline group, an equal volume of physiological saline was administered and the blood flow velocity in the LITA was recorded continuously by the transthoracic Doppler method from the supraclavicular fossa approach. Results; ATP administration increased the blood flow velocity in the LITA and the rate of increase was 48.3% for systolic peak velocity, 111% for diastolic peak velocity, 64.4% for systolic time velocity integral and 99% for diastolic time velocity integral indicating particularly high rates of increase in diastolic components. The diastolic/systolic peak velocity ratio or diastolic fraction did not increase significantly. In the saline group, none of the parameters showed a change. 2) Angiographic findings of the LITA were compared with the measurement values of the diastolic components by the Doppler method to examine usefulness of diastolic component measurement with ATP infusion for diagnosis of LITA patency. Subjects were 19 patients with good LITA (group A) and 8 patients with bad LITA (group B). Results; while there were significant differences in the mean baseline diastolic peak velocity, mean diastolic time velocity integral and mean diastolic fraction between the groups, overlapping was seen in individual cases. However, the inter-group differences were more distinct by ATP infusion and the borderline values were 30 cm/sec for diastolic peak velocity and 10 for diastolic time velocity integral. 3) Reliability of the

  8. Toxicology and Carcinogenesis Studies of 4,4'-Diamino-2,2'-Stilbenedisulfonic Acid Disodium Salt (CAS No. 7336-20-1) in F344 Rats and B6C3F1 Mice (Feed Studies).

    PubMed

    1992-08-01

    4,4'-Diamino-2,2'-stilbenedisulfonic acid, disodium salt, is used in the synthesis of dyes and optical brighteners or fluorescent whitening agents. Toxicology and carcinogenesis studies were conducted by administering the chemical (approximately 14% water, 6% sodium chloride, 4% impurities, and 76% 4,4'-diamino-2,2'-stilbenedisulfonic acid) in feed to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 14-Day Studies: Groups of five rats and five mice of each sex were given 0, 6,250, 12,500, 25,000, 50,000, or 100,000 ppm 4,4'-diamino-2,2'-stilbenedisulfonic acid, disodium salt, in feed for 14 days. All rats and mice survived to the end of the studies. The mean body weight gain of male rats receiving 50,000 or 100,000 ppm and of female rats and male and female mice receiving 100,000 ppm was significantly lower than those of the respective controls. Clinical findings included diarrhea in the rats and mice receiving 100,000 ppm. There were no chemical-related changes in absolute or relative organ weights in rats or mice. There were no gross or microscopic lesions related to chemical administration in rats or mice. 13-Week Studies: Groups of 10 rats and 10 mice of each sex were given 0, 6,250, 12,500, 25,000, 50,000, or 100,000 ppm 4,4'-diamino-2,2'-stilbenedisulfonic acid, disodium salt, in feed for 13 weeks. One female rat, six male mice, and one female mouse in the 100,000 ppm dose groups died during the studies. Mean body weight gain was significantly decreased in male rats and female mice receiving 50,000 or 100,000 ppm, in male mice receiving 25,000, 50,000, or 100,000 ppm, and in female rats receiving 100,000 ppm. Clinical findings in rats that received 50,000 or 100,000 ppm and in mice that received 100,000 ppm included diarrhea, emaciation, and hyperemia of the perineum. There were no biologically significant changes in

  9. Sequential-injection determination of traces of disodium phenyl dibenzimidazole tetrasulphonate in urine from users of sunscreens by on-line solid-phase extraction coupled with a fluorimetric detector.

    PubMed

    Balaguer, A; Chisvert, A; Salvador, A

    2006-03-01

    A sensitive and selective method to determine disodium phenyl dibenzimidazole tetrasulphonate (PDT) in the urine of sunscreen users, which is suitable for studies on body accumulation/excretion is proposed. On-line solid-phase extraction allows the analyte to be retained and subsequentely eluted, using a strong anion exchange (SAX) microcolumn. Standard addition calibration was carried out with only one standard. The wavelengths of excitation and emission were 330 and 454 nm, respectively. The method allows PDT to be determined in both, spiked and unspiked human urine samples, without any pre-treatment. Results obtained for spiked urine samples (40-200 ng ml(-1)) showed the accuracy of the method. The mean relative standard deviations (R.S.D.) of the results was 7%. Five volunteers applied a sunscreen lotion containing 5% PDT and their urinary excretion was controlled from the moment of application until the excreted amounts were no longer detectable. The sensitivity of the proposed method is in the order of 1900 ml microg(-1) and the detection limit (3S(y/x)/b) is in the order of 5 ng of PDT, which means 10 ng ml(-1) for a 500 microl injected volume, and this is suitable for the PDT levels found in the urine.

  10. Dissolution Properties of Dihydroxylammonium 5,5ʹ-Bistetrazole-1,1ʹ-diolate and Disodium 5,5ʹ-Bistetrazole-1,1ʹ-diolate in Water

    NASA Astrophysics Data System (ADS)

    Niu, Hu; Chen, Shusen; Jin, Shaohua; Shu, Qinghai; Li, Lijie; Shang, Fengqin

    2016-10-01

    The dissolution and thermochemical properties of dihydroxylammonium 5,5ʹ-bistetrazole-1,1ʹ-diolate (TKX-50) and its intermedium disodium 5,5ʹ-bistetrazole-1,1ʹ-diolate ([Na2(H2O)4]BTO) in water at 298.15 K were studied using a C-80 Calvet microcalorimeter. Empirical formulae for the calculation of the molar enthalpies of dissolution (ΔdissH), relative partial molar enthalpies (ΔdissHpartial), and relative apparent molar enthalpies (ΔdissHapparent) were deduced by the experimental results of the dissolution processes of TKX-50 and [Na2(H2O)4]BTO in water. Finally, the corresponding kinetic equations describing the dissolution processes were dα/dt = 10-2.95(1 - α)0.64 for the dissolution of TKX-50 in water and dα/dt = 10-2.76(1 - α)1.07 for the dissolution of [Na2(H2O)4]BTO in water.

  11. Concentration-Induced J-Aggregate Formation Causes a Biphasic Change in the Release of trans-Combretastatin A4 Disodium Phosphate from Archaeosomes and the Subsequent Cytotoxicity on Mammary Cancer Cells.

    PubMed

    Daswani, Varsha P; Ayesa, Umme; Venegas, Berenice; Chong, Parkson Lee-Gau

    2015-10-01

    Combretastatin A4 disodium phosphate (CA4P) is a fluorescent, water-soluble prodrug able to induce vascular shutdown within tumors at doses less than one-tenth of the maximum tolerated dose. As a continued effort to develop efficient liposomal CA4P to treat solid tumor, we herein investigate the physical and spectroscopic properties of CA4P in aqueous solution and the mechanism of CA4P release from archaeal tetraether liposomes (archaeosomes). We found that cis-CA4P can be photoisomerized to trans-CA4P. This photoisomerization results in an increase in fluorescence intensity. Both cis- and trans-CA4P undergo fluorescence intensity self-quenching after they reach a critical concentration Cq (∼0.15-0.25 mM). Moreover, both cis- and trans-CA4P in buffer exhibit a red shift in their excitation spectrum and an increase in excitation spectrum band sharpness with increasing concentration, which can be attributed to the formation of J-aggregates. The onset of the dramatic change in excitation maximum occurs at concentrations close to Cq, suggesting that the self-quenching arises from extensive J-aggregate formation and that, when CA4P concentration exceeds Cq, J-aggregate formation begins to increase sharply. Our data also suggest that the extent of J-aggregate formation plays a critical role in CA4P release from tetraether archaeosomes and in the subsequent cytotoxicity on cultured human breast cancer MCF-7 cells. The drug leakage and cytotoxicity rate constants vary with the initial CA4P concentration entrapped inside archaeosomes in a biphasic manner, reaching a local maximum at 0.25-0.50 mM. A mechanism based on the concept of J-aggregate formation has been proposed to explain the biphasic changes in drug release and cytotoxicity with increasing drug concentration. Tetraether archaeosomes are extraordinarily stable and relatively nontoxic to animals; thus, they are promising nano drug carriers. The results obtained from this study pave the way for future development

  12. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... products containing dried bananas 2 315 Promote color retention. Salad dressing 75 Preservative. Sandwich... Do. Salad dressing 75 Do. Sandwich spread 100 Do. Sauces 75 Do. (3) Alone, as a sequestrant in...

  13. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... products containing dried bananas 2 315 Promote color retention. Salad dressing 75 Preservative. Sandwich... Do. Salad dressing 75 Do. Sandwich spread 100 Do. Sauces 75 Do. (3) Alone, as a sequestrant in...

  14. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Promote color retention. Pink beans (cooked canned) 165 Promote color retention. Potato salad 100... color retention. Salad dressing 75 Preservative. Sandwich spread 100 Do. Sauces 75 Do. Shrimp (cooked... Preservative. French dressing 75 Do. Mayonnaise 75 Do. Salad dressing 75 Do. Sandwich spread 100 Do. Sauces...

  15. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... Potato salad 100 Preservative. Processed dry pinto beans 800 Promote color retention. Red beans (cooked canned) 165 Promote color retention. Salad dressing 75 Preservative. Sandwich spread 100 Do. Sauces 75 Do...) Use Dressings, nonstandardized 75 Preservative. French dressing 75 Do. Mayonnaise 75 Do....

  16. In vivo effect of triptolide combined with glycyrrhetinic acid on rat cytochrome P450 enzymes.

    PubMed

    Han, Feng-Mei; Peng, Zhi-Hong; Wang, Jun-Jun; Chen, Yong

    2013-07-01

    Triptolide (TP) is a major active component in Tripterygium root, but its therapeutic window was very narrow due to its severe multi-organ toxicity. In this work, the effect of TP combined with glycyrrhetic acid (GA) on mRNA expression and activity of four cytochrome P450 (CYP) enzymes in rat liver was studied after intragastric administration of TP (0.05, 0.3 and 0.6 mg x kg(-1) x day(-1)) and TP (0.6 mg x kg(-1) x day(-1)) combined with GA (30 mg x kg(-1) x day(-1)) for 7 consecutive days. Compared with the control, the high dose of TP significantly up-regulated the mRNA expression levels of CYP2E1, 1A2, 3A1 and 2C11, the co-administration of TP and GA further up-regulated the mRNA expression levels of CYP3A1, 2C11 and 2E1 as compared with the high dose of TP. Meanwhile, TP at high dose and combined with GA significantly increased CYP3A-associated testosterone 6beta-hydroxylation activity (2.2-fold and 4.1-fold, respectively) as compared with the control. Because TP is mainly metabolized by CYP3A2 in male rats, the present work indicated that TP-induced increase of CYP3A activity might be an important reason for the rapidly metabolic clearance of TP in rat liver, and GA can reduce the hepatotoxicity of TP by promoting its hepatic metabolic clearance. Furthermore, the results also suggest that the drug interactions might be occurred when TP and GA were co-administered with other CYP3A substrate drug.

  17. MRI With Gadoxetate Disodium in Measuring Tumors in Patients With Liver Cancer

    ClinicalTrials.gov

    2015-10-14

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage 0 Adult Hepatocellular Carcinoma; BCLC Stage A Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Localized Resectable Adult Liver Carcinoma

  18. Disodium 4,5,6-trihy­droxy­benzene-1,3-disulfonate dihydrate

    PubMed Central

    Song, E.; Podschun, J.; Wilberts, H.; Beginn, U.; Reuter, H.

    2010-01-01

    In the title compound, 2Na+·C6H4O9S2 2−·2H2O, the benzene rings of the 4,5,6-trihy­droxy­benzene-1,3-disulfonate ions, which are stacked parallel to each other forming rods parallel to the a axis, are slightly deformed (planarity, symmetry) mainly because of the high degree of substitution. The two sodium ions, located within pockets of the anion rods, are coordinated by six and seven O atoms, resulting in octa­hedral and penta­gonal-bipyramidal coordinations, respectively. In addition to these coordinative bonds towards sodium, an extended network of intra- and inter­molecular hydrogen bonds occurs. PMID:21587412

  19. Pemetrexed Disodium in the Cerebrospinal Fluid of Patients With Leptomeningeal Metastases

    ClinicalTrials.gov

    2015-04-09

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Metastatic Cancer; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Precancerous Condition; Secondary Myelofibrosis; Unspecified Adult Solid Tumor, Protocol Specific

  20. Disodium diaqua-bis-(methyl-enedi-phos-pho-nato-κO,O')cobaltate(II) dihydrate.

    PubMed

    van Merwe, Kina; Visser, Hendrik G; Venter, Johan A

    2011-10-01

    In the title compound, Na(2)[Co(CH(4)O(6)P(2))(2)(H(2)O)(2)]·2H(2)O, the asymmetric unit is composed of one methyl-enediphospho-nate ligand and one water mol-ecule, which both are coordinated to a Co(II) atom, as well as a non-coordinated water mol-ecule and a sodium cation. The Co(II) atom occupies a special position on a crystallographic inversion centre. The slightly distorted Co(II)O(6) octa-hedral coordination environment is composed of two bidentate methyl-enediphospho-nate ligands and two coordinated water mol-ecules in trans positions. The sodium ion is octa-hedrally coordinated to six O atoms with Na-O distances ranging from 2.3149 (12) to 2.6243 (12) Å. An extensive three-dimensional network of inter-molecular as well as intra-molecular O-H⋯O and C-H⋯O hydrogen bonding inter-acions is present. PMID:22058722

  1. A potential adjuvant chemotherapeutics, 18β-glycyrrhetinic acid, inhibits renal tubular epithelial cells apoptosis via enhancing BMP-7 epigenetically through targeting HDAC2

    PubMed Central

    Ma, Taotao; Huang, Cheng; Meng, Xiaoming; Li, Xiaofeng; Zhang, Yilong; Ji, Shuai; Li, Jun; Ye, Min; Liang, Hong

    2016-01-01

    Cisplatin, a highly effective and widely used chemotherapeutic agent, has a major limitation for its nephrotoxicity. We recently identified a novel strategy for attenuating its nephrotoxicity in chemotherapy by an effective adjuvant via epigenetic modification through targeting HDAC2. Molecular docking and SPR assay firstly reported that 18βGA, major metabolite of GA, could directly bind to HDAC2 and inhibit the activity of HDAC2. The effects and mechanisms of GA and 18βGA were assessed in CP-induced AKI in C57BL/6 mice, and in CP-treated HK-2 and mTEC cells lines. TUNEL and FCM results confirmed that GA and 18βGA could inhibit apoptosis of renal tubular epithelial cells induced by CP in vivo and in vitro. Western blot and immunofluorescence results demonstrated that the expression of BMP-7 was clearly induced by 18βGA in AKI models while siRNA BMP-7 could reduce the inhibitory effect of 18βGA on apoptosis. Results of current study indicated that 18βGA inhibited apoptosis of renal tubular epithelial cells via enhancing the level of BMP-7 epigenetically through targeting HDAC2, therefore protecting against CP-induced AKI. These available evidence, which led to an improved understanding of molecular recognition, suggested that 18βGA could serve as a potential clinical adjuvant in chemotherapy. PMID:27145860

  2. Effects of Orally Administered Pyrroloquinoline Quinone Disodium Salt on Dry Skin Conditions in Mice and Healthy Female Subjects.

    PubMed

    Nakano, Masahiko; Kamimura, Ayako; Watanabe, Fumiko; Kamiya, Toshikazu; Watanabe, Daisuke; Yamamoto, Etsushi; Fukagawa, Mitsuhiko; Hasumi, Keiji; Suzuki, Eriko

    2015-01-01

    Pyrroloquinoline quinone (PQQ) is a coenzyme involved in the redox-cycling system. The supplemental use of PQQ has been examined based on its properties as an antioxidant and redox modulator. Although an animal study on deficiency of PQQ suggested that PQQ contributes to skin conditions, its efficacy in humans has not been reported. The present study aimed to investigate the effects of orally administered PQQ on skin moisture, viscoelasticity, and transepidermal water loss (TEWL) both in dry skin mouse models and in healthy female subjects with a subjective symptom of dry skin. In our dry skin mouse model study, oral intake of PQQ (0.0089%, w/w, in the diet for 6 wk) significantly decreased the number of mast cells in the dermis and the number of CD3⁺ T-cells in the epidermis. In our human study, oral intake of PQQ (20 mg/d for 8 wk) significantly inhibited the increase in TEWL on the forearm. Finally, subject questionnaires showed positive impressions for the improvement of skin conditions. These results suggest that oral intake of PQQ improves skin conditions both in female subjects with dry skin and in mice with a compromised skin barrier function.

  3. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  4. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  5. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  6. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  7. 40 CFR 180.1121 - Boric acid and its salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Boric acid and its salts, borax... EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Exemptions From Tolerances § 180.1121 Boric acid and its... the requirement of a tolerance is established for residues of the pesticidal chemical boric acid...

  8. Effects of Orally Administered Pyrroloquinoline Quinone Disodium Salt on Dry Skin Conditions in Mice and Healthy Female Subjects.

    PubMed

    Nakano, Masahiko; Kamimura, Ayako; Watanabe, Fumiko; Kamiya, Toshikazu; Watanabe, Daisuke; Yamamoto, Etsushi; Fukagawa, Mitsuhiko; Hasumi, Keiji; Suzuki, Eriko

    2015-01-01

    Pyrroloquinoline quinone (PQQ) is a coenzyme involved in the redox-cycling system. The supplemental use of PQQ has been examined based on its properties as an antioxidant and redox modulator. Although an animal study on deficiency of PQQ suggested that PQQ contributes to skin conditions, its efficacy in humans has not been reported. The present study aimed to investigate the effects of orally administered PQQ on skin moisture, viscoelasticity, and transepidermal water loss (TEWL) both in dry skin mouse models and in healthy female subjects with a subjective symptom of dry skin. In our dry skin mouse model study, oral intake of PQQ (0.0089%, w/w, in the diet for 6 wk) significantly decreased the number of mast cells in the dermis and the number of CD3⁺ T-cells in the epidermis. In our human study, oral intake of PQQ (20 mg/d for 8 wk) significantly inhibited the increase in TEWL on the forearm. Finally, subject questionnaires showed positive impressions for the improvement of skin conditions. These results suggest that oral intake of PQQ improves skin conditions both in female subjects with dry skin and in mice with a compromised skin barrier function. PMID:26226961

  9. Comparative effects of vetiver oil, nootkatone and disodium octaborate tetrahydrate on Coptotermes formosanus and its symbiotic fauna.

    PubMed

    Maistrello, Lara; Henderson, Gregg; Laine, Roger A

    2003-01-01

    The potential of vetiver oil and nootkatone as wood treatments against Coptotermes formosanus Shiraki was examined by assessing the effects on termite tunneling, feeding activity and survival, and the consequences on the symbiont protozoa responsible for wood digestion. Comparisons were made with non-treated wood (control), wood treated with the borate compound Tim-Bor (a commonly used lumber preservative) and absence of a food source (starved termites), using choice and no-choice tests. All wood slices were prepared at the same time using a 10 g liter(-1) solution of each substance and were tested in four different sessions over one year to investigate longevity of the effects. Termites had to tunnel through sand to exploit the food sources, consisting of two wood slices, placed on opposite sides of the experimental enclosure. No-choice tests showed that in the presence of vetiver oil or nootkatone, tunneling activity was always the lowest; wood consumption, termite survival and flagellate numbers and species distribution were significantly different from the control and similar to the results obtained for starved termites and with Tim-Bor-treated wood. Nootkatone negatively affected termites for 12 months and was longer lasting than vetiver oil. In choice tests, when vetiver oil or nootkatone were present, termites exhibited a significant preference for non-treated wood. Our results confirmed both the toxicity and absence of repellency of Tim-Bor. Vetiver oil and especially nootkatone affected Formosan subterranean termites and their protozoa, acting as arrestants, repellents and feeding deterrents, and represent a promising natural alternative for the control of this invasive pest. PMID:12558100

  10. A correlation between antioxidant activity and metabolite release during the blanching of Chrysanthemum coronarium L.

    PubMed

    Kim, Jiyoung; Choi, Jung Nam; Ku, Kang Mo; Kang, Daejung; Kim, Jong Sang; Park, Jung Han Yoon; Lee, Choong Hwan

    2011-01-01

    Liquid chromatography tandem mass spectrometry (LCMS/MS)-based metabolite profiling was applied to elucidate the correlation between metabolite release and antioxidant activity during water blanching of Chrysanthemum coronarium L. (CC). Some major metabolites showing differences between fresh CC and blanched CC (BCC) were selected by principal component analysis (PCA) and partial least-square discriminate analysis (PLS-DA) loading plots, and were identified as dicaffeoylquinic acid (DCQA), succinoyl-DCQA, and acetylmycosinol. By PLS regression analysis of the correlation between antioxidant components and effects, candidate antioxidative metabolites were predicted due to strong positive correlations with DCQA and succinoyl-DCQA, and by a relatively weak positive correlation with acetylmycosinol.

  11. Methoxyamine, Pemetrexed Disodium, Cisplatin, and Radiation Therapy in Treating Patients With Stage IIIA-IV Non-small Cell Lung Cancer

    ClinicalTrials.gov

    2016-10-05

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma; Stage IIIA Lung Adenocarcinoma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIB Large Cell Lung Carcinoma; Stage IIIB Lung Adenocarcinoma; Stage IIIB Non-Small Cell Lung Cancer; Stage IV Large Cell Lung Carcinoma; Stage IV Lung Adenocarcinoma; Stage IV Non-Small Cell Lung Cancer

  12. Synthesis and properties of novel sulfonated polybenzimidazoles from disodium 4,6-bis(4-carboxyphenoxy)benzene-1,3-disulfonate

    NASA Astrophysics Data System (ADS)

    Sheng, Li; Xu, Hongjie; Guo, Xiaoxia; Fang, Jianhua; Fang, Liang; Yin, Jie

    2011-03-01

    A series of sulfonated polybenzimidazoles (SPBIs) with varied ion exchange capacities (IECs) have been synthesized by random condensation copolymerization of a new sulfonated dicarboxylic acid monomer 4,6-bis(4-carboxyphenoxy)benzene-1,3-disulfonate (BCPOBDS-Na), 4,4‧-dicarboxydiphenyl ether (DCDPE) and 3,3‧-diaminobenzidine (DAB) in Eaton's reagent at 140 °C. Most of the SPBIs show good solubility in polar aprotic organic solvents such as dimethylsulfoxide (DMSO) and N,N-dimethylacetamide (DMAc). Thermogravimetric analysis (TGA) reveals that the SPBIs have excellent thermal stability (desulfonation temperatures (on-set) > 370 °C). The SPBI membranes show good mechanical properties of which tensile strength, elongation at break, and storage modulus are in the range of 89-96 MPa, 12-42%, and 2.4-3.1 GPa, respectively. Moreover, the SPBI membranes exhibit phosphoric acid (PA) uptake in the range of 180-240% (w/w) in 85 wt% PA at 50 °C, while high mechanical properties (13-20 MPa) are maintained. The SPBI membrane with 240% (w/w) PA uptake displays fairly high proton conductivity (37.3 mS cm-1) at 0% relative humidity at 170 °C. The fuel cell fabricated with the PA-doped SPBI membrane (PA uptake = 240% (w/w)) displays good performance with the highest output power density of 0.58 W cm-2 at 170 °C with hydrogen-oxygen gases under ambient pressure without external humidification.

  13. [The accuracy and side effects of pharmacologic stress thallium myocardial scintigraphy with adenosine triphosphate disodium (ATP) infusion in the diagnosis of coronary artery disease].

    PubMed

    Kinoshita, S; Suzuki, S; Shindou, A; Watanabe, K; Muramatsu, T; Ide, M; Dohi, Y; Yamashita, S; Suzuki, T; Nishimura, K

    1994-08-01

    The diagnostic accuracy and side effects of pharmacologic stress thallium myocardial scintigraphy with ATP infusion were studied in 172 patients with or without coronary artery disease. ATP was infused for five minutes at a rate of 0.16 mg/kg/min (group A) or 0.18 mg/kg/min (group B) via antecubital vein. One hundred and eleven (67 of group A, 44 of group B) of 172 patients underwent coronary arteriography (CAG). In 111 patients received CAG, overall sensitivity, specificity and accuracy of this method were 88%, 84% and 87%, respectively. In 67 patients of group A, these were 92%, 81% and 90%. In 44 patients of group B, 79%, 87% and 82% were documented (NS, between group A and B). Chest pain, flushing, bradycardia and ST depression were included in side effects caused by ATP infusion. At least one of these side effects were observed in 84% of the all 172 patients, 89% of group A and 75% of group B (NS). But, all of the side effects were spontaneously alleviated within two minutes without any therapy. In conclusion, pharmacologic stress myocardial scintigraphy with ATP infusion is very accurate and safe, and infusion rate of 0.16 mg/kg/min is optimal for this purpose. PMID:7933682

  14. Response of immune response genes to adjuvants poly [di(sodium carboxylatoethylphenoxy)phosphazene] (PCEP), CpG oligodeoxynucleotide and emulsigen at intradermal injection site in pigs.

    PubMed

    Magiri, R B; Lai, K; Chaffey, A M; Wilson, H L; Berry, W E; Szafron, M L; Mutwiri, G K

    2016-07-01

    Understanding the mechanisms by which adjuvants mediate their effects provide critical information on how innate immunity influences the development of adaptive immunity. Despite being a critical vaccine component, the mechanisms by which adjuvants mediate their effects are not fully understood and this is especially true when they are used in large animals. This lack of understanding limits our ability to design effective vaccines. In the present study, we administered polyphosphazene (PCEP), CpG oligodeoxynucleotides (CpG), emulsigen or saline via an intradermal injection into pigs and assessed the impact on the expression of reported 'adjuvant response genes' over time. CpG induced a strong upregulation of the chemokine CXL10 several 'Interferon Response Genes', as well as TNFα, and IL-10, and a down-regulation of IL-17 genes. Emulsigen upregulated expression of chemokines CCL2 and CCL5, proinflammatory cytokines IL-6 and TNFα, as well as TLR9, and several IFN response genes. PCEP induced the expression of chemokine CCL2 and proinflammatory cytokine IL-6. These results suggest that emulsigen and CpG may promote recruitment of innate immune cells and Th1 type cytokine production but that PCEP may promote a Th-2 type immune response through the induction of IL-6, an inducer of B cell activity and differentiation. PMID:27269793

  15. Glycyrrhetinic acid induces cytoprotective autophagy via the inositol-requiring enzyme 1α-c-Jun N-terminal kinase cascade in non-small cell lung cancer cells.

    PubMed

    Tang, Zheng-Hai; Zhang, Le-Le; Li, Ting; Lu, Jia-Hong; Ma, Dik-Lung; Leung, Chung-Hang; Chen, Xiu-Ping; Jiang, Hu-Lin; Wang, Yi-Tao; Lu, Jin-Jian

    2015-12-22

    Glycerrhetinic acid (GA), one of the main bioactive constituents of Glycyrrhiza uralensis Fisch, exerts anti-cancer effects on various cancer cells. We confirmed that GA inhibited cell proliferation and induced apoptosis in non-small cell lung cancer A549 and NCI-H1299 cells. GA also induced expression of autophagy marker phosphatidylethanolamine-modified microtubule-associated protein light-chain 3 (LC3-II) and punta formation of green fluorescent protein microtubule-associated protein light-chain 3. We further proved that expression of GA-increased autophagy marker was attributed to activation instead of suppression of autophagic flux. The c-jun N-terminal kinase (JNK) pathway was activated after incubation with GA. Pretreatment with the JNK inhibitor SP600125 or silencing of the JNK pathway by siRNA of JNK or c-jun decreased GA-induced autophagy. The endoplasmic reticulum (ER) stress responses were also apparently stimulated by GA by triggering the inositol-requiring enzyme 1α (IRE1α) pathway. The GA-induced JNK pathway activation and autophagy were decreased by IRE1α knockdown, and inhibition of autophagy or the JNK cascade increased GA-stimulated IRE1α expression. In addition, GA-induced cell proliferative inhibition and apoptosis were increased by inhibition of autophagy or the JNK pathway. Our study was the first to demonstrate that GA induces cytoprotective autophagy in non-small cell lung cancer cells by activating the IRE1α-JNK/c-jun pathway. The combined treatment of autophagy inhibitors markedly enhances the anti-neoplasmic activity of GA. Such combination shows potential as a strategy for GA or GA-contained prescriptions in cancer therapy.

  16. How to Read a Food Label: Tips for People with Chronic Kidney Disease (CKD)

    MedlinePlus

    ... foods with potassium on the ingredient list. Ingredients: Tomato juice, Vegetable juice blend, Potassium chloride, Sugar, Magnesium, Salt, Vitamin C (Ascorbic acid), Citric acid, Spice extract, Flavoring, Disodium inosinate, Disodium ...

  17. Calcium Free Asbestos for Fuel Cells

    NASA Technical Reports Server (NTRS)

    Snitzer, B. A.

    1983-01-01

    Organic-acid salt removes unwanted calcium without weakening asbestos. Asbestos mixed with disodium ethylene diamine tetraacetic acid (disodium EDTA) in water and agitated for 2 hours. After disodium EDTA solution is drained away, asbestos contains only 0.02 to 0.1 percent calcium. Fiber structure of asbestos unaffected.

  18. Biodegradation of nicotine by a novel strain Pusillimonas.

    PubMed

    Ma, Yun; Wen, Rongti; Qiu, Jiguo; Hong, Jun; Liu, Meng; Zhang, Dou

    2015-01-01

    A novel strain, Pusillimonas sp. T2, which is capable of degrading nicotine, was isolated and identified. This strain could completely degrade 500 mg/L nicotine within 8 h at 30 °C, pH 7.0. Six intermediates were detected and identified as 6-hydroxy-nicotine, 6-hydroxy-N-methylmyosmine, 6-hydroxypseudooxynicotine, 2,6-dihydroxypyridine, 6-hydroxy-3-succinoyl-pyridine and 2,5-dihydroxypyridine. Activities of 6-hydroxy-3-succinoyl-pyridine hydroxylase and 2,6-dihydroxypyridine hydroxylase were demonstrated in the cell extracts of strain T2, indicating that this strain may employ a novel variant of the pyridine and pyrrolidine pathways that is different from those of other species. This study provides the first evidence that Pusillimonas bacteria participate in nicotine degradation.

  19. The effect of HPMCAS functional groups on drug crystallization from the supersaturated state and dissolution improvement.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2014-04-10

    The inhibitory effect on drug crystallization in aqueous solution was evaluated using various forms of hydroxypropyl methylcellulose acetate succinate (HPMCAS). HPMCAS suppressed crystallization of carbamazepine (CBZ), nifedipine (NIF), mefenamic acid, and dexamethasone. The inhibition of drug crystallization mainly derived from molecular level hydrophobic interactions between the drug and HPMCAS. HPMCAS with a lower succinoyl substituent ratio strongly suppressed drug crystallization. The inhibition of crystallization was affected by pH, with the CBZ crystallization being inhibited at a higher pH due to the hydrophilization of HPMCAS derived from succinoyl ionization. The molecular mobility of CBZ in an HPMCAS solution was evaluated by 1D-(1)H NMR and relaxation time measurements. CBZ mobility was strongly suppressed in the HPMCAS solutions where strong inhibitory effects on CBZ crystallization were observed. The mobility suppression of CBZ in the HPMCAS solution was derived from intermolecular interactions between CBZ and HPMCAS leading to an inhibition of crystallization. The effect of HPMCAS on the drug dissolution rate was evaluated using an NIF/HPMCAS solid dispersion. The dissolution rate of NIF was increased when HPMCAS with a higher succinoyl substituent ratio was used.

  20. Identification and characterization of five new classes of chlorogenic acids in burdock (Arctium lappa L.) roots by liquid chromatography/tandem mass spectrometry.

    PubMed

    Jaiswal, Rakesh; Kuhnert, Nikolai

    2011-01-01

    Burdock (Arcticum lappa L.) roots are used in folk medicine and also as a vegetable in Asian countries especially Japan, Korea, and Thailand. We have used LC-MS(n) (n = 2-4) to detect and characterize in burdock roots 15 quantitatively minor fumaric, succinic, and malic acid-containing chlorogenic acids, 11 of them not previously reported in nature. These comprise 3-succinoyl-4,5-dicaffeoyl or 1-succinoyl-3,4-dicaffeoylquinic acid, 1,5-dicaffeoyl-3-succinoylquinic acid, 1,5-dicaffeoyl-4-succinoylquinic acid, and 3,4-dicaffeoyl-5-succinoylquinic acid (M(r) 616); 1,3-dicaffeoyl-5-fumaroylquinic acid and 1,5-dicaffeoyl-4-fumaroylquinic acid (M(r) 614); 1,5-dicaffeoyl-3-maloylquinic acid, 1,4-dicaffeoyl-3-maloylquinic acid, and 1,5-dicaffeoyl-4-maloylquinic acid (M(r) 632); 1,3,5-tricaffeoyl-4-succinoylquinic acid (M(r) 778); 1,5-dicaffeoyl-3,4-disuccinoylquinic acid (M(r) 716); 1,5-dicaffeoyl-3-fumaroyl-4-succinoylquinic acid and 1-fumaroyl-3,5-dicaffeoyl-4-succinoylquinic acid (M(r) 714); dicaffeoyl-dimaloylquinic acid (M(r) 748); and 1,5-dicaffeoyl-3-succinoyl-4-dimaloylquinic acid (M(r) 732). All the structures have been assigned on the basis of LC-MS(n) patterns of fragmentation, relative hydrophobicity, and analogy of fragmentation patterns if compared to caffeoylquinic acids.

  1. Methoxyamine, Cisplatin, and Pemetrexed Disodium in Treating Patients With Advanced Solid Tumors or Mesothelioma That Cannot Be Removed by Surgery or Mesothelioma That Is Refractory to Cisplatin and Pemetrexed

    ClinicalTrials.gov

    2016-09-09

    Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Solid Neoplasm; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pleural Mesothelioma; Thymoma

  2. Is lead chelation therapy effective for chronic kidney disease? A meta-analysis.

    PubMed

    Yang, Shi-Kun; Xiao, Li; Song, Pan-Ai; Xu, Xiao-Xuan; Liu, Fu-You; Sun, Lin

    2014-01-01

    The heavy metal lead (Pb) is a major environmental and occupational hazard. Epidemiological studies have demonstrated a strong association between lead exposure and the presence of chronic kidney injury. Some studies have suggested that chelation therapy with calcium disodium ethylenediaminetetraacetic acid (calcium disodium EDTA) might help decrease the progression of chronic kidney disease among patients with measurable body lead burdens. However, calcium disodium EDTA chelation in lead exposure is controversial due to the potential for adverse effects such as acute tubular necrosis. Therefore, we investigated the available randomized controlled trials assessing the renoprotective effects of calcium disodium EDTA chelation therapy. Our meta-analysis shows that calcium disodium EDTA chelation therapy can effectively delay the progression of chronic kidney disease in patients with measurable body lead burdens reflected by increasing the levels of estimated glomerular filtration rate (eGFR) and creatinine clearance rate (Ccr). There appears to be no conclusive evidence that calcium disodium EDTA can decrease proteinuria.

  3. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Disodium salt of 6,6′-oxybis (2-naphthalene-sulfonic acid), not more than 1.0 percent. Lead (as Pb), not... Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2) Color...-naphthalenesulfonic acid, not more than 1.0 percent. Sodium salt of 6-hydroxy-2-naphthalenesulfonic acid...

  4. 21 CFR 137.305 - Enriched farina.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... salts of iron or calcium, or from any added disodium phosphate, or from any added wheat germ or partly... and not more than 0.87 mg of folic acid, and not less than 13.0 mg of iron (Fe). (2) Vitamin D may be... by weight of the optional ingredient disodium phosphate; or (ii) It may be treated with one of...

  5. 21 CFR 74.102 - FD&C Blue No. 2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Blue No. 2 is principally the disodium salt of 2-(1,3-dihydro-3-oxo-5-sulfo-2H-indol-2-ylidene)-2,3-dihydro-3-oxo-1H-indole-5-sulfonic acid (CAS Reg. No. 860-22-0) with smaller amounts of the disodium salt... Reg. No. 54947-75-0) and the sodium salt of...

  6. 21 CFR 74.102 - FD&C Blue No. 2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Blue No. 2 is principally the disodium salt of 2-(1,3-dihydro-3-oxo-5-sulfo-2H-indol-2-ylidene)-2,3-dihydro-3-oxo-1H-indole-5-sulfonic acid (CAS Reg. No. 860-22-0) with smaller amounts of the disodium salt... Reg. No. 54947-75-0) and the sodium salt of...

  7. 21 CFR 74.203 - FD&C Green No. 3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-aminobenzenesulfonic acid) to sodium 5-amino-2-formylbenzenesulfonate. This amine is diazotized and the resulting...&C Green No. 3 is principally the inner salt disodium salt of N-ethyl-N- amino]phenyl](4-hydroxy-2...-45-9); with smaller amounts of the isomeric inner salt disodium salt of N-ethyl-N-...

  8. 21 CFR 74.203 - FD&C Green No. 3.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...-aminobenzenesulfonic acid) to sodium 5-amino-2-formylbenzenesulfonate. This amine is diazotized and the resulting...&C Green No. 3 is principally the inner salt disodium salt of N-ethyl-N- amino]phenyl](4-hydroxy-2...-45-9); with smaller amounts of the isomeric inner salt disodium salt of N-ethyl-N-...

  9. 21 CFR 74.203 - FD&C Green No. 3.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...-aminobenzenesulfonic acid) to sodium 5-amino-2-formylbenzenesulfonate. This amine is diazotized and the resulting...&C Green No. 3 is principally the inner salt disodium salt of N-ethyl-N- amino]phenyl](4-hydroxy-2...-45-9); with smaller amounts of the isomeric inner salt disodium salt of N-ethyl-N-...

  10. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  11. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  12. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  13. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  14. 21 CFR 74.203 - FD&C Green No. 3.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-aminobenzenesulfonic acid) to sodium 5-amino-2-formylbenzenesulfonate. This amine is diazotized and the resulting...&C Green No. 3 is principally the inner salt disodium salt of N-ethyl-N- amino]phenyl](4-hydroxy-2...-45-9); with smaller amounts of the isomeric inner salt disodium salt of N-ethyl-N-...

  15. 21 CFR 74.203 - FD&C Green No. 3.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...-aminobenzenesulfonic acid) to sodium 5-amino-2-formylbenzenesulfonate. This amine is diazotized and the resulting...&C Green No. 3 is principally the inner salt disodium salt of N-ethyl-N- amino]phenyl](4-hydroxy-2...-45-9); with smaller amounts of the isomeric inner salt disodium salt of N-ethyl-N-...

  16. 40 CFR 721.9795 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[(4,6-dichloro-1,3,5-triazin-2-yl) amino...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Benzenesulfonic acid, 2,2â²-(1,2... Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with dialkyl amines (generic). (a... generically as a benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis -, disodium salt, substituted with...

  17. [Comparison of two extraction methods for maxingshigan decoction].

    PubMed

    Zhang, Z; Sun, X; Wang, L; Liu, H; Lu, Q

    1997-07-01

    The semi-bionic extraction and the extraction with water, two methods for the Maxingshigan Decoction, were compared. The results show that the semi-bionic extraction is superior to the extraction with water in the yield of ephedrine, hydrocyanic acid, glycyrrhetinic acid, calcium ion and extract. PMID:11038900

  18. Crystal structure of the inverse crown ether tetra­kis­[μ2-bis­(tri­methyl­sil­yl)amido]-μ4-oxido-dicobalt(II)disodium, [Co2Na2{μ2-N(SiMe3)2}4](μ4-O)

    PubMed Central

    Hansen, Christopher B.; Filatov, Alexander S.; Hillhouse, Gregory L.

    2016-01-01

    The title compound, [Co2Na2{μ2-N(SiMe3)2}4](μ4-O), (I), represents a new entry in the class of inverse crown ethers. In the mol­ecule, each Co atom is formally in the oxidation state +II. The structure contains one half of a unique mol­ecule per asymmetric unit with the central μ4-oxido ligand residing on an inversion center, leading to a planar coordination to the Na and Co atoms. In the crystal, bulky tri­methyl­silyl substituents prevent additional inter­actions with cobalt. However, weak inter­molecular Na⋯H3C—Si inter­actions form an infinite chain along [010]. The structure is isotypic with its Mg, Mn and Zn analogues. PMID:27308041

  19. Drugs Approved for Malignant Mesothelioma

    MedlinePlus

    ... Professionals Questions to Ask about Your Treatment Research Drugs Approved for Malignant Mesothelioma This page lists cancer ... in malignant mesothelioma that are not listed here. Drugs Approved for Malignant Mesothelioma Alimta (Pemetrexed Disodium) Pemetrexed ...

  20. 21 CFR 529.2464 - Ticarcillin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Specifications. Each vial contains ticarcillin disodium powder equivalent to 6 grams of ticarcillin for... 6 grams daily by intrauterine infusion for 3 consecutive days during estrus. (2) Indications for...

  1. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  2. Prediction of bioavailability of selected bisphosphonates using in silico methods towards categorization into a biopharmaceutical classification system.

    PubMed

    Biernacka, Joanna; Betlejewska-Kielak, Katarzyna; Kłosińska-Szmurło, Ewa; Pluciński, Franciszek A; Mazurek, Aleksander P

    2013-01-01

    The physicochemical properties relevant to biological activity of selected bisphosphonates such as clodronate disodium salt, etidronate disodium salt, pamidronate disodium salt, alendronate sodium salt, ibandronate sodium salt, risedronate sodium salt and zoledronate disodium salt were determined using in silico methods. The main aim of our research was to investigate and propose molecular determinants thataffect bioavailability of above mentioned compounds. These determinants are: stabilization energy (deltaE), free energy of solvation (deltaG(solv)), electrostatic potential, dipole moment, as well as partition and distribution coefficients estimated by the log P and log D values. Presented values indicate that selected bisphosphonates a recharacterized by high solubility and low permeability. The calculated parameters describing both solubility and permeability through biological membranes seem to be a good bioavailability indicators of bisphosphonates examined and can be a useful tool to include into Biopharmaceutical Classification System (BCS) development.

  3. Sodium carbonate poisoning

    MedlinePlus

    Sal soda poisoning; Soda ash poisoning; Disodium salt poisoning; Carbonic acid poisoning; Washing soda poisoning ... number will let you talk to experts in poisoning. They will give you further instructions. This is ...

  4. 21 CFR 177.1580 - Polycarbonate resins.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... optional adjuvant substances required in the production of the resins; or by (2) The reaction of molten 4,4′-iso-propylidenediphenol with molten diphenyl carbonate in the presence of the disodium salt of...

  5. 21 CFR 177.1580 - Polycarbonate resins.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... optional adjuvant substances required in the production of the resins; or by (2) The reaction of molten 4,4′-iso-propylidenediphenol with molten diphenyl carbonate in the presence of the disodium salt of...

  6. 21 CFR 522.161 - Betamethasone.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Betamethasone. (a) Specifications. Each milliliter of suspension contains: (1) Betamethasone acetate equivalent to 10.8 milligrams (mg) betamethasone and betamethasone disodium phosphate equivalent to 3 mg of betamethasone. (2) Betamethasone dipropionate equivalent to 5 mg betamethasone and betamethasone...

  7. 21 CFR 133.169 - Pasteurized process cheese.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... following: Monosodium phosphate, disodium phosphate, dipotassium phosphate, trisodium phosphate, sodium metaphosphate (sodium hexametaphosphate), sodium acid pyrophosphate, tetrasodium pyrophosphate, sodium aluminum phosphate, sodium citrate, potassium citrate, calcium citrate, sodium tartrate, and sodium...

  8. 21 CFR 178.3570 - Lubricants with incidental food contact.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... CFR Sections Affected, which appears in the Finding Aids section of the printed volume and at www... exceed 2 percent by weight of the grease. Disodium EDTA (CAS Reg. No. 139-33-3) For use only as...

  9. 21 CFR 178.3570 - Lubricants with incidental food contact.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... CFR Sections Affected, which appears in the Finding Aids section of the printed volume and at www... exceed 2 percent by weight of the grease. Disodium EDTA (CAS Reg. No. 139-33-3) For use only as...

  10. 21 CFR 178.3570 - Lubricants with incidental food contact.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... CFR Sections Affected, which appears in the Finding Aids section of the printed volume and at www... exceed 2 percent by weight of the grease. Disodium EDTA (CAS Reg. No. 139-33-3) For use only as...

  11. 40 CFR 116.4 - Designation of hazardous substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 631618 Acetic acid ammonium, salt Ammonium benzoate 1863634 Ammonium bicarbonate 1066337 Acid ammonium... Silver nitrate 7761888 Nitric acid silver (1+) salt lunar caustic Sodium 7440235 Natrium Sodium arsenate 7631892 Disodium arsenate Sodium arsenite 7784465 Sodium metaarsenite Sodium bichromate 10588019...

  12. 40 CFR 116.4 - Designation of hazardous substances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 631618 Acetic acid ammonium, salt Ammonium benzoate 1863634 Ammonium bicarbonate 1066337 Acid ammonium... Silver nitrate 7761888 Nitric acid silver (1+) salt lunar caustic Sodium 7440235 Natrium Sodium arsenate 7631892 Disodium arsenate Sodium arsenite 7784465 Sodium metaarsenite Sodium bichromate 10588019...

  13. 40 CFR 116.4 - Designation of hazardous substances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 631618 Acetic acid ammonium, salt Ammonium benzoate 1863634 Ammonium bicarbonate 1066337 Acid ammonium... Silver nitrate 7761888 Nitric acid silver (1+) salt lunar caustic Sodium 7440235 Natrium Sodium arsenate 7631892 Disodium arsenate Sodium arsenite 7784465 Sodium metaarsenite Sodium bichromate 10588019...

  14. 40 CFR 116.4 - Designation of hazardous substances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 631618 Acetic acid ammonium, salt Ammonium benzoate 1863634 Ammonium bicarbonate 1066337 Acid ammonium... Silver nitrate 7761888 Nitric acid silver (1+) salt lunar caustic Sodium 7440235 Natrium Sodium arsenate 7631892 Disodium arsenate Sodium arsenite 7784465 Sodium metaarsenite Sodium bichromate 10588019...

  15. 40 CFR 116.4 - Designation of hazardous substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 631618 Acetic acid ammonium, salt Ammonium benzoate 1863634 Ammonium bicarbonate 1066337 Acid ammonium... Silver nitrate 7761888 Nitric acid silver (1+) salt lunar caustic Sodium 7440235 Natrium Sodium arsenate 7631892 Disodium arsenate Sodium arsenite 7784465 Sodium metaarsenite Sodium bichromate 10588019...

  16. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  17. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  18. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate. Magnesium stearate....

  19. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...: Aluminum mono-, di-, and tristearate. Ammonium citrate. Ammonium potassium hydrogen phosphate. Calcium glycerophosphate. Calcium phosphate. Calcium hydrogen phosphate. Calcium oleate. Calcium acetate. Calcium carbonate. Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate....

  20. Application of Novel Nonlinear Optical Materials to Optical Processing

    NASA Technical Reports Server (NTRS)

    Banerjee, Partha P.

    1999-01-01

    We describe wave mixing and interactions in nonlinear photorefractive polymers and disodium flourescein. Higher diffracted orders yielding forward phase conjugation can be generated in a two-wave mixing geometry in photorefractive polymers, and this higher order can be used for image edge enhancement and correlation. Four-wave mixing and phase conjugation is studied using nonlinear disodium floureschein, and the nature and properties of gratings written in this material are investigated.

  1. 21 CFR 74.1322 - D&C Red No. 22.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Red No. 22 is principally the disodium salt of 2′,4′,5′7′-tetrabromofluorescein (CAS Reg. No. 17372-87-1) and may contain smaller amounts of the disodium salts of 2′,4′,5′-tribromofluorescein and 2′,4′,7... for drug use made with Red No. 22 may contain only those diluents that are suitable and that...

  2. Toxicity and repellency of borate-sucrose water baits to Argentine ants (Hymenoptera: Formicidae).

    PubMed

    Klotz, J H; Greenberg, L; Amrhein, C; Rust, M K

    2000-08-01

    The oral toxicity of boron compounds to the Argentine ant, Linepithema humile (Mayr), was evaluated in laboratory tests. The ants were provided 25% sucrose water containing 0.5 and 1% boric acid, disodium octaborate tetrahydrate, and borax. Lethal times of these solutions were a function of the concentration of boron. In field tests, the ants showed no discrimination between disodium octaborate tetrahydrate and boric acid. There was a significant reduction in consumption of sucrose water with > 1% boric acid.

  3. First Occurrence of a Furano-glycyrrhetinoate and Its Cytotoxicity.

    PubMed

    Heller, Lucie; Sommerwerk, Sven; Tzschöckell, Felix; Wiemann, Jana; Schwarz, Stefan; Siewert, Bianka; Al-Harrasi, Ahmed; Csuk, René

    2015-12-01

    (18α)-Glycyrrhetinic acid (4) was prepared from (18β)-glycyrrhetinic acid (1), and the cytotoxicity of some derivatives was investigated by photometric SRB assays employing several human tumor cell lines. In summary, (18β)-1 is slightly more cytotoxic than its (18α) epimer 4, but its cytotoxicity is negligible. Higher cytotoxicity was observed for the esters 2 and 5 and for the 3-O-acetylated esters 3 and 6. Cytotoxicity was improved dramatically when the hydroxyl group at position C-3 was replaced by an amino moiety. SeO2 oxidations gave access to a novel furano-glycyrrhetinoate 15. Interestingly, its seleno analog 16 is approximately five to six times less cytotoxic for the tumor cell lines tested, and tumor/non-tumor selectivity is lost upon replacement of the oxygen by a selenium substituent. PMID:26548762

  4. Inhibitory effect of hydroxypropyl methylcellulose acetate succinate on drug recrystallization from a supersaturated solution assessed using nuclear magnetic resonance measurements.

    PubMed

    Ueda, Keisuke; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2013-10-01

    We examined the inhibitory effect of hydroxypropyl methylcellulose acetate succinate (HPMC-AS) on drug recrystallization from a supersaturated solution using carbamazepine (CBZ) and phenytoin (PHT) as model drugs. HPMC-AS HF grade (HF) inhibited the recrystallization of CBZ more strongly than that by HPMC-AS LF grade (LF). 1D-1H NMR measurements showed that the molecular mobility of CBZ was clearly suppressed in the HF solution compared to that in the LF solution. Interaction between CBZ and HF in a supersaturated solution was directly detected using nuclear Overhauser effect spectroscopy (NOESY). The cross-peak intensity obtained using NOESY of HF protons with CBZ aromatic protons was greater than that with the amide proton, which indicated that CBZ had hydrophobic interactions with HF in a supersaturated solution. In contrast, no interaction was observed between CBZ and LF in the LF solution. Saturation transfer difference NMR measurement was used to determine the interaction sites between CBZ and HF. Strong interaction with CBZ was observed with the acetyl substituent of HPMC-AS although the interaction with the succinoyl substituent was quite small. The acetyl groups played an important role in the hydrophobic interaction between HF and CBZ. In addition, HF appeared to be more hydrophobic than LF because of the smaller ratio of the succinoyl substituent. This might be responsible for the strong hydrophobic interaction between HF and CBZ. The intermolecular interactions between CBZ and HPMC-AS shown by using NMR spectroscopy clearly explained the strength of inhibition of HPMC-AS on drug recrystallization.

  5. Stability of acetylcysteine in an extemporaneously compounded ophthalmic solution.

    PubMed

    Anaizi, N H; Swenson, C F; Dentinger, P J

    1997-03-01

    The stability of acetylcysteine in an extemporaneously compounded ophthalmic solution was studied. Acetylcysteine 10% ophthalmic solution containing 0.025% disodium edetate and 0.5% chlorobutanol in an artificial tears base was prepared and stored at 2-8 degrees C in clear, 15-mL, low-density polyethylene dropper bottles. At 0, 7, 14, 21, 28, 35, and 60 days, a 1-mL sample was removed from each bottle and analyzed for acetylcysteine concentration by high-performance liquid chromatography. Another set of 10% acetylcysteine solutions containing 0.025%, 0.050%, 0.075%, or 0.10% disodium edetate were prepared, stored at room temperature (23-25 degrees C), and analyzed at 0, 7, 15, 30, 40, and 50 days. In the solutions containing 0.025% disodium edetate, acetylcysteine was stable for 60 days at 2-8 degrees C but for less than 7 days at 23-25 degrees C. In the solutions containing 0.75% and 0.10% disodium edetate, acetylcysteine was stable for 40 and 50 days, respectively, at 23-25 degrees C. Acetylcysteine in a 10% acetylcysteine ophthalmic solution containing 0.025% disodium edetate and 0.5% chlorobutanol in an artificial tears base was stable for 60 days at 2-8 degrees C.

  6. 21 CFR 74.1205 - D&C Green No. 5.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1205 D&C Green No. 5. (a) Identity. (1) The color additive D&C Green No. 5 is principally the disodium salt of 2,2′- bis- (CAS Reg. No. 4403-90-1). (2) Color...

  7. 21 CFR 74.1205 - D&C Green No. 5.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1205 D&C Green No. 5. (a) Identity. (1) The color additive D&C Green No. 5 is principally the disodium salt of 2,2′- bis- (CAS Reg. No. 4403-90-1). (2) Color...

  8. 21 CFR 74.1333 - D&C Red No. 33.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Red No. 33 is principally the disodium salt of 5-amino-4-hydroxy-3-(phenylazo)-2,7-naphthalenedisulfonic acid (CAS Reg. No. 3567-66-6). To manufacture the additive, the product obtained from the nitrous acid diazotization of aniline is coupled with 4-hydroxy-5-amino-2,7-naphthalenedisulfonic acid in...

  9. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... compound is coupled with 6-hydroxy-2-naphthalene-sulfonic acid. The dye is isolated as the sodium salt and...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg....

  10. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... compound is coupled with 6-hydroxy-2-naphthalene-sulfonic acid. The dye is isolated as the sodium salt and...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg....

  11. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... compound is coupled with 6-hydroxy-2-naphthalene-sulfonic acid. The dye is isolated as the sodium salt and...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg....

  12. 75 FR 13277 - Notice of Receipt of Several Pesticide Petitions Filed for Residues of Pesticide Chemicals in or...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-19

    ... exemption from the requirement of a tolerance for residues of sodium and potassium salts of N-alkyl (C 8 - C... following sodium and potassium salts of N-alkyl (C 8 - C 18 )-beta-iminodipropionic acid where the C 8 - C...-(2-carboxyethyl)-N-tallow alkyl derivatives-, disodium salts (61791-56-8); -alanine,...

  13. A field method for the determination of calcium and magnesium in limestone and dolomite

    USGS Publications Warehouse

    Shapiro, Leonard; Brannock, Walter Wallace

    1957-01-01

    The method is an adaptation of a procedure described by Betz and Noll1 in 1950. Calcium and magnesium are determined by visual titration using Versene (disodium ethylenediamine tetraacetate) with Murexide (ammonium purpurate) as the indicator for calcium and Eriochrome Black T as the indicator for magnesium.

  14. Dynamic NMR of Intramolecular Exchange Processes in EDTA Complexes of Sc[superscript 3+], Y[superscript 3+], and La[superscript 3+

    ERIC Educational Resources Information Center

    Ba, Yong; Han, Steven; Ni, Lily; Su, Tony; Garcia, Andres

    2006-01-01

    Dynamic NMR makes use of the effect of chemical exchanges on NMR spectra to study kinetics and thermodynamics. An advanced physical chemistry lab experiment was developed to study the intramolecular exchange processes of EDTA (the disodium salt of ethylenediaminetetraacetic acid) metal complexes. EDTA is an important chelating agent, used in…

  15. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., and methacrylic acid applied in emulsion form to molded virgin fiber and heat-cured to an insoluble... application of the emulsion may include substances named in this paragraph, in an amount not to exceed that... emulsion defoamer. Disodium hydrogen phosphate Do. Formaldehyde Glyceryl monostearate Methyl...

  16. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of 4′,5... drug use made with D&C Orange No. 11 may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring externally applied drugs. (b) Specifications....

  17. 21 CFR 74.250 - Orange B.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... principally the disodium salt of 1-(4-sulfophenyl)-3-ethylcarboxy-4-(4-sulfonaphthylazo)-5-hydro-xypyrazole. (2) The diluents in color additive mixtures for food use containing Orange B are limited to those... than 6.0 percent. Chlorides and sulfates (calculated as the sodium salts), not more than 7.0...

  18. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2) Color additive mixtures for food use (including dietary supplements) made with FD&C Red No. 40 may contain only those diluents that are suitable and that are listed in part 73 of this chapter as safe for use in...

  19. 21 CFR 74.1328 - D&C Red No. 28.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Red No. 28 is principally the disodium salt of 2′,4′,5′,7′-tetrabromo-4,5,6,7-tetrachlorofluorescein.... (2) Color additive mixtures for drug use made with D&C Red No. 28 may contain only those diluents that are suitable and that are listed in part 73 of this chapter as safe for use in color...

  20. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg. No... compound is coupled with 6-hydroxy-2-naphthalene-sulfonic acid. The dye is isolated as the sodium salt...

  1. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2) Color additive mixtures for use in externally applied drugs made with FD&C Red No. 4 may contain only those diluents that are suitable and that are listed in part 73 of this chapter for use in color...

  2. 21 CFR 74.303 - FD&C Red No. 3.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-xanthen-3-one, disodium salt, with smaller amounts of lower imdinated fluoresceins. (2) Color additive mixtures for food use made with FD&C Red No. 3 may contain only those diluents that are suitable and that are listed in part 73 of this chapter as safe for use in color additive mixtures for coloring...

  3. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of 4′,5... drug use made with D&C Orange No. 11 may contain only those diluents listed in this subpart as safe and suitable for use in color additive mixtures for coloring externally applied drugs. (b) Specifications....

  4. 21 CFR 74.1708 - D&C Yellow No. 8.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...&C Yellow No. 8 is principally the disodium salt of fluorescein. (2) Color additive mixtures for use... suitable and that are listed in part 73 of this chapter for use in color additive mixtures for coloring... chlorides and sulfates (calculated as sodium salts), not more than 15 percent. Matter insoluble in...

  5. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...&C Yellow No. 6 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid (CAS Reg. No. 2783-94-0). The trisodium salt of 3-hydroxy-4- -2,7-naphthalenedisulfonic acid (CAS Reg. No... compound is coupled with 6-hydroxy-2-naphthalene-sulfonic acid. The dye is isolated as the sodium salt...

  6. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... than 0.2 percent. 5-Amino-2,4-dimethyl-1-benzenesulfonic acid, sodium salt, not more than 0.2 percent. 4-Hydroxy-1-naphthalenesulfonic acid, sodium salt, not more than 0.2 percent. Subsidiary colors, not... Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

  7. 21 CFR 178.3570 - Lubricants with incidental food contact.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... affecting § 178.3570, see the List of CFR Sections Affected, which appears in the Finding Aids section of.... Disodium EDTA (CAS Reg. No. 139-33-3) For use only as a chelating agent and sequestrant at a level not...

  8. 21 CFR 74.1322 - D&C Red No. 22.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...′-tribromofluorescein. The color additive is manufactured by alkaline hydrolysis of 2′,4′,5′,7′-tetrabromofluorescein. 2... soduim salts), not more than 10 percent. Water-insoluble matter not more than 0.5 percent. Disodium...

  9. 21 CFR 74.1322 - D&C Red No. 22.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...′-tribromofluorescein. The color additive is manufactured by alkaline hydrolysis of 2′,4′,5′,7′-tetrabromofluorescein. 2... soduim salts), not more than 10 percent. Water-insoluble matter not more than 0.5 percent. Disodium...

  10. 21 CFR 74.1328 - D&C Red No. 28.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Red No. 28. 74.1328 Section 74.1328 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1328 D&C Red No. 28. (a) Identity. (1) The color additive D&C Red No. 28 is principally the disodium salt of...

  11. 21 CFR 74.1333 - D&C Red No. 33.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Red No. 33 is principally the disodium salt of 5-amino-4-hydroxy-3-(phenylazo)-2,7-naphthalenedisulfonic acid (CAS Reg. No. 3567-66-6). To manufacture the additive, the product obtained from the nitrous acid diazotization of aniline is coupled with 4-hydroxy-5-amino-2,7-naphthalenedisulfonic acid in...

  12. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with...-Amino-5-methylbenzenesulfonic acid, sodium salt, not more than 0.2 percent....

  13. 21 CFR 74.1333 - D&C Red No. 33.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Red No. 33 is principally the disodium salt of 5-amino-4-hydroxy-3-(phenylazo)-2,7-naphthalenedisulfonic acid (CAS Reg. No. 3567-66-6). To manufacture the additive, the product obtained from the nitrous acid diazotization of aniline is coupled with 4-hydroxy-5-amino-2,7-naphthalenedisulfonic acid in...

  14. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with...-Amino-5-methylbenzenesulfonic acid, sodium salt, not more than 0.2 percent....

  15. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with hydrochloric acid and sodium nitrite. The diazo compound is coupled in alkaline medium with...

  16. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with...-Amino-5-methylbenzenesulfonic acid, sodium salt, not more than 0.2 percent....

  17. 21 CFR 74.1333 - D&C Red No. 33.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Red No. 33 is principally the disodium salt of 5-amino-4-hydroxy-3-(phenylazo)-2,7-naphthalenedisulfonic acid (CAS Reg. No. 3567-66-6). To manufacture the additive, the product obtained from the nitrous acid diazotization of aniline is coupled with 4-hydroxy-5-amino-2,7-naphthalenedisulfonic acid in...

  18. 21 CFR 74.1333 - D&C Red No. 33.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Red No. 33 is principally the disodium salt of 5-amino-4-hydroxy-3-(phenylazo)-2,7-naphthalenedisulfonic acid (CAS Reg. No. 3567-66-6). To manufacture the additive, the product obtained from the nitrous acid diazotization of aniline is coupled with 4-hydroxy-5-amino-2,7-naphthalenedisulfonic acid in...

  19. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... than 0.2 percent. 5-Amino-2,4-dimethyl-1-benzenesulfonic acid, sodium salt, not more than 0.2 percent. 4-Hydroxy-1-naphthalenesulfonic acid, sodium salt, not more than 0.2 percent. Subsidiary colors, not... Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

  20. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...-naphthalenesulfonic acid, not more than 1.0 percent. Sodium salt of 6-hydroxy-2-naphthalenesulfonic acid (Schaeffer's salt), not more than 0.3 percent. 4-Amino-5-methoxy-o- toluenesulfonic acid, not more than 0.2 percent... Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2)...

  1. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Red No. 6 is principally the disodium salt of 3-hydroxy-4- -2-naphthalenecarboxylic acid (CAS Reg. No. 5858-81-1). To manufacture the additive, 2-amino-5-methylbenzenesulfonic acid is diazotized with hydrochloric acid and sodium nitrite. The diazo compound is coupled in alkaline medium with...

  2. 21 CFR 529.2464 - Ticarcillin powder.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Ticarcillin powder. 529.2464 Section 529.2464 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL... powder. (a) Specifications. Each vial contains ticarcillin disodium equivalent to 6 grams of...

  3. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches

    PubMed Central

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  4. (3β,18β,20β)-N-Eth­oxy­carbonyl­methyl-3-nitrato-11-oxoolean-12-ene-29-carboxamide methanol monosolvate

    PubMed Central

    Czollner, Laszlo; Jordis, Ulrich; Mereiter, Kurt

    2012-01-01

    The title compound, C34H52N2O7·CH4O, is the methanol solvate of a difunctionalized derivative of the therapeutic agent 18β-glycyrrhetinic acid, a penta­cyclic triterpene. The five six-membered rings of the glycyrrhetinic acid moiety show normal geometries, with four rings in chair conformations and the unsaturated ring in a half-chair conformation. This moiety is substituted by a nitrate ester group and an O-ethyl­glycine group. In the crystal, the nonsolvent mol­ecules are packed parallel to (010) in a herringbone fashion with the nitrato, ethyl­glycine and methanol-O atom being proximate. The methanol solvent mol­ecule is anchored via a donated O—H⋯Oac­yl and an accepted N—H⋯O hydrogen bond, giving rise to infinite zigzag chains of hydrogen bonds parallel to [100]. Two weak intermolecular C—H⋯O interactions to the methanol and to an acyl oxygen establish links along [100] and [010], respectively. PMID:22606164

  5. Pseudohyperaldosteronism: pathogenetic mechanisms.

    PubMed

    Armanini, Decio; Calò, Lorenzo; Semplicini, Andrea

    2003-06-01

    Pseudohyperaldosteronism is characterized by a clinical picture of hyperaldosteronism with suppression of plasma renin activity and aldosterone. Pseudohyperaldosteronism can be due to a direct mineralocorticoid effect, as with desoxycorticosterone, fluorohydrocortisone, fluoroprednisolone, estrogens, and the ingestion of high amounts of glycyrrhetinic acid. A block of 11-hydroxysteroid-dehydrogenase type 2 (11HSD2), the enzyme that converts cortisol into cortisone, at the level of epithelial target tissues of aldosterone, is involved in other cases. This mechanism is related either to a mutation of the gene, which encodes 11HSD2 (apparent mineralocorticoid excess syndrome and some cases of low renin hypertension) or to an acquired reduction of the activity of the enzyme due to glycyrrhetinic acid, carbenoxolone, and grapefruit juice. In other cases saturation of 11HSD2 may be involved as in severe Cushing's syndrome and chronic therapy with some corticosteroids. Recently, an activating mutation of the mineralocorticoid receptor gene has been described. Another genetic cause of pseudohyperaldosteronism is the syndrome of Liddle, which is due to a mutation of the gene encoding for beta and gamma subunits of the sodium channels. PMID:12892318

  6. 11β-hydroxysteroid dehydrogenase inhibition as a new potential therapeutic target for alcohol abuse

    PubMed Central

    Sanna, P P; Kawamura, T; Chen, J; Koob, G F; Roberts, A J; Vendruscolo, L F; Repunte-Canonigo, V

    2016-01-01

    The identification of new and more effective treatments for alcohol abuse remains a priority. Alcohol intake activates glucocorticoids, which have a key role in alcohol's reinforcing properties. Glucocorticoid effects are modulated in part by the activity of 11β-hydroxysteroid dehydrogenases (11β-HSD) acting as pre-receptors. Here, we tested the effects on alcohol intake of the 11β-HSD inhibitor carbenoxolone (CBX, 18β-glycyrrhetinic acid 3β-O-hemisuccinate), which has been extensively used in the clinic for the treatment of gastritis and peptic ulcer and is active on both 11β-HSD1 and 11β-HSD2 isoforms. We observed that CBX reduces both baseline and excessive drinking in rats and mice. The CBX diastereomer 18α-glycyrrhetinic acid 3β-O-hemisuccinate (αCBX), which we found to be selective for 11β-HSD2, was also effective in reducing alcohol drinking in mice. Thus, 11β-HSD inhibitors may be a promising new class of candidate alcohol abuse medications, and existing 11β-HSD inhibitor drugs may be potentially re-purposed for alcohol abuse treatment. PMID:26978742

  7. Novel Chemical Ligands to Ebola Virus and Marburg Virus Nucleoproteins Identified by Combining Affinity Mass Spectrometry and Metabolomics Approaches.

    PubMed

    Fu, Xu; Wang, Zhihua; Li, Lixin; Dong, Shishang; Li, Zhucui; Jiang, Zhenzuo; Wang, Yuefei; Shui, Wenqing

    2016-01-01

    The nucleoprotein (NP) of Ebola virus (EBOV) and Marburg virus (MARV) is an essential component of the viral ribonucleoprotein complex and significantly impacts replication and transcription of the viral RNA genome. Although NP is regarded as a promising antiviral druggable target, no chemical ligands have been reported to interact with EBOV NP or MARV NP. We identified two compounds from a traditional Chinese medicine Gancao (licorice root) that can bind both NPs by combining affinity mass spectrometry and metabolomics approaches. These two ligands, 18β-glycyrrhetinic acid and licochalcone A, were verified by defined compound mixture screens and further characterized with individual ligand binding assays. Accompanying biophysical analyses demonstrate that binding of 18β-glycyrrhetinic acid to EBOV NP significantly reduces protein thermal stability, induces formation of large NP oligomers, and disrupts the critical association of viral ssRNA with NP complexes whereas the compound showed no such activity on MARV NP. Our study has revealed the substantial potential of new analytical techniques in ligand discovery from natural herb resources. In addition, identification of a chemical ligand that influences the oligomeric state and RNA-binding function of EBOV NP sheds new light on antiviral drug development. PMID:27403722

  8. Hemolytic activity of a bacterial trehalose lipid biosurfactant produced by Rhodococcus sp.: evidence for a colloid-osmotic mechanism.

    PubMed

    Zaragoza, Ana; Aranda, Francisco J; Espuny, María J; Teruel, José A; Marqués, Ana; Manresa, Angeles; Ortiz, Antonio

    2010-06-01

    A succinoyl trehalose lipid produced by Rhodococcus sp. behaves as a biological surfactant and also displays various interesting biological activities. Trehalose lipid has been shown to have a great tendency to partition into phospholipid membranes; therefore, the characterization of its interaction with biological membranes is of central importance. In this work, human red blood cells have been used as an experimental model. Trehalose lipid causes the swelling of human erythrocytes followed by hemolysis at concentrations well below its critical micellar concentration. Kinetic measurements show that, upon addition of trehalose lipid, K(+) release precedes that of hemoglobin. Osmotic protectants of the appropriate size added to the external medium make it possible to avoid hemolysis. The results indicate that trehalose lipid causes the hemolysis of human erythrocytes by a colloid-osmotic mechanism, most likely by formation of enhanced permeability domains, or "pores" enriched in the biosurfactant, within the erythrocyte membrane. Scanning electron microscopy shows trehalose lipid-induced spherocytosis and echinocytosis of red blood cells, which fits well within the framework of the bilayer-couple hypothesis. The presented results contribute to establishing a molecular basis for the biological properties of this trehalose lipid biosurfactant. PMID:20146489

  9. Correlation of length of linear oligo(ethanamino) amides with gene transfer and cytotoxicity.

    PubMed

    Scholz, Claudia; Kos, Petra; Leclercq, Laurent; Jin, Xiaoyun; Cottet, Hervé; Wagner, Ernst

    2014-09-01

    The optimization of synthetic carriers for gene transfer remains a major challenge. Cationic polymers such as polyethylenimine (PEI) often show increasing gene transfer activity with increasing molecular weight, but this favorable effect is accompanied by an undesired increase in cytotoxicity. Moreover, the polydispersity of polymers prevents accurate determination of optimum size. Herein we describe the step-by-step elongation of precise linear oligo(ethanamino) amides by making use of the artificial amino acid succinoyl-tetraethylene pentamine (Stp) for solid-phase-assisted synthesis. This procedure enabled us to identify the optimal oligomer Stp30-W (8.4 kDa) with a length of 30 Stp units, with which effective gene transfer occurs in the absence of cytotoxicity. The transfection efficiency of Stp30-W exceeded that of standard linear PEI (22 kDa) by sixfold; nevertheless, Stp30-W exhibited tenfold lower cytotoxicity. In addition to the lower molecular weight, the succinate spacer between the oligoamine units may also contribute to the favorable biocompatibility. The cytotoxicity of the cationic polymer PEI is a major concern for use as a carrier for gene delivery, so this comparison between linear PEI and the new Stp oligomers is particularly relevant.

  10. Intracellular sorting of differently charged chitosan derivatives and chitosan-based nanoparticles

    NASA Astrophysics Data System (ADS)

    Zubareva, A. A.; Shcherbinina, T. S.; Varlamov, V. P.; Svirshchevskaya, E. V.

    2015-04-01

    Chitosan (Chi) is a biodegradable nontoxic polycation with multiple reactive groups that is easily used to obtain derivatives with a desired charge and hydrophobic properties. The aim of this work was to study the intracellular traffic of positively charged hexanoyl-chitosan (HC) or HC-based nanoparticles (HCNPs) and negatively charged succinoyl-chitosan (SC) and SCNPs in epithelial and macrophage cell lines. By using flow cytometry we demonstrated that positively charged HC adhered to cell membranes quicker and more efficiently than negatively charged SC or NPs. However confocal studies showed that SC and SCNPs penetrated cells much more efficiently than HC while HCNPs did not enter the epithelial cells. Macrophages also phagocyted better negatively charged material but were able to engulf both HC and HCNPs. Upon entering the cells, SC and SCNPs were co-localized with endosomes and lysosomes while HC was found in mitochondria and, to a lesser extent, in lysosomes of epithelial cells. Macrophages, RAW264.7, more efficiently transported all Chi samples to the lysosomal compartment while some positively charged material was still found in mitochondria. Incubation of Chi derivatives and ChiNPs at pH specific to mitochondria (8.0) and lysosomes (4.5) demonstrated the neutralization of Chi charge. We concluded that epithelial cells and, to a lesser extent, macrophages sort charged material to the organelles neutralizing Chi charge.

  11. Molecular cloning and functional characterization of the diapause hormone receptor in the corn earworm Helicoverpa zea

    PubMed Central

    Jiang, Hongbo; Wei, Zhaojun; Nachman, Ronald J.; Park, Yoonseong

    2013-01-01

    The diapause hormone (DH) in the heliothine moth has shown its activity in termination of pupal diapause, while the orthology in the silkworm is known to induce embryonic diapause. In the current study, we cloned the diapause hormone receptor from the corn earworm Helicoverpa zea (HzDHr) and tested its ligand specificities in a heterologous reporter system. HzDHr was expressed in Chinese Hamster Ovary (CHO) cells, which were co-transfected with the aequorin reporter, and was used to measure the ligand activities. A total of 68 chemicals, including natural DH analogs and structurally similar peptide mimetics, were tested for agonistic and antagonistic activities. Several peptide mimetics with a 2-amino-7-bromofluorene-succinoyl (2Abf-Suc) N-terminal modification showed strong agonistic activities; these mimetics included 2Abf-Suc-F[dA]PRLamide, 2Abf-Suc-F[dR]PRLamide, 2Abf-Suc-FKPRLamide and 2Abf-Suc-FGPRLamide. Antagonistic activity was found in the ecdysis triggering hormone in Drosophila melanogaster (FFLKITKNVPRLamide). Interestingly, HzDHr does not discriminate between DH (WFGPRLamide C-terminal motif) and another closely related endogenous peptide, pyrokinin 1 (FXPRXamide; a C-terminal motif that is separate from WFGPRLamide). We provide large-scale in vitro data that serve as a reference for the development of agonists and antagonists to disrupt the DH signaling pathway. PMID:24257143

  12. Modelling drug degradation in a spray dried polymer dispersion using a modified Arrhenius equation.

    PubMed

    Patterson, Adele; Ferreira, Ana P; Banks, Elizabeth; Skeene, Kirsty; Clarke, Graham; Nicholson, Sarah; Rawlinson-Malone, Clare

    2015-01-15

    The Pharmaceutical industry is increasingly utilizing amorphous technologies to overcome solubility challenges. A common approach is the use of drug in polymer dispersions to prevent recrystallization of the amorphous drug. Understanding the factors affecting chemical and physical degradation of the drug within these complex systems, e.g., temperature and relative humidity, is an important step in the selection of a lead formulation, and development of appropriate packaging/storage control strategies. The Arrhenius equation has been used as the basis of a number of models to predict the chemical stability of formulated product. In this work, we investigate the increase in chemical degradation seen for one particular spray dried dispersion formulation using hydroxypropyl methylcellulose acetate succinate (HPMC-AS). Samples, prepared using polymers with different substitution levels, were placed on storage for 6 months under a range of different temperature and relative humidity conditions and the degradant level monitored using high-performance liquid chromatography (HPLC). While the data clearly illustrates the impact of temperature and relative humidity on the degradant levels detected, it also highlighted that these terms do not account for all the variability in the data. An extension of the Arrhenius equation to include a term for the polymer chemistry, specifically the degree of succinoyl substitution on the polymer backbone, was shown to improve the fit of the model to the data.

  13. Modelling drug degradation in a spray dried polymer dispersion using a modified Arrhenius equation.

    PubMed

    Patterson, Adele; Ferreira, Ana P; Banks, Elizabeth; Skeene, Kirsty; Clarke, Graham; Nicholson, Sarah; Rawlinson-Malone, Clare

    2015-01-15

    The Pharmaceutical industry is increasingly utilizing amorphous technologies to overcome solubility challenges. A common approach is the use of drug in polymer dispersions to prevent recrystallization of the amorphous drug. Understanding the factors affecting chemical and physical degradation of the drug within these complex systems, e.g., temperature and relative humidity, is an important step in the selection of a lead formulation, and development of appropriate packaging/storage control strategies. The Arrhenius equation has been used as the basis of a number of models to predict the chemical stability of formulated product. In this work, we investigate the increase in chemical degradation seen for one particular spray dried dispersion formulation using hydroxypropyl methylcellulose acetate succinate (HPMC-AS). Samples, prepared using polymers with different substitution levels, were placed on storage for 6 months under a range of different temperature and relative humidity conditions and the degradant level monitored using high-performance liquid chromatography (HPLC). While the data clearly illustrates the impact of temperature and relative humidity on the degradant levels detected, it also highlighted that these terms do not account for all the variability in the data. An extension of the Arrhenius equation to include a term for the polymer chemistry, specifically the degree of succinoyl substitution on the polymer backbone, was shown to improve the fit of the model to the data. PMID:25450477

  14. The neurite-initiating effect of microbial extracellular glycolipids in PC12 cells.

    PubMed

    Isoda, H; Shinmoto, H; Matsumura, M; Nakahara, T

    1999-09-01

    The effects of several kinds of microbial extracellular glycolipids on neurite initiation in PC12 cells were examined. Addition of mannosylerythritol lipid-A (MEL-A), MEL-B, and sophorose lipid (SL) to PC12 cells caused significant neurite outgrowth. Other glycolipids, such as polyol lipid (PL), rhamnose lipid (RL), succinoyl trehalose lipid-A (STL-A) and STL-B caused no neurite-initiation. MEL-A increased acetylcholine esterase (AChE) activity to an extent similar to nerve growth factor (NGF). However, MEL-A induced one or two long neurites from the cell body, while NGF induced many neurites. In addition, MEL-A-induced differentiation was transient, and after 48 h, percentage of cells with neurites started to decrease in contrast to neurons induced by NGF, which occurred in a time-dependent manner. MEL-A could induce neurite outgrowth after treatment of PC12 cells with an anti-NGF receptor antibody that obstructed NGF action. These results indicate that MEL-A and NGF induce differentiation of PC12 cells through different mechanisms. PMID:19003137

  15. Pharmacokinetics of Maxing Shigan decoction in normal rats and RSV pneumonia model rats by HPLC-MS/MS.

    PubMed

    Jiang, Li; Gao, Meng; Qu, Fei; Li, Hui-lan; Yu, Lan-bin; Rao, Yi; Wang, Yue-sheng; Xu, Guo-liang

    2015-07-01

    To establish a LC-MS/MS method to determine the concentrations of liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine of Maxing Shigan decoction in rat plasma, and study the differences on their pharmacokinetic process in normal rats and RSV pneumonia model rats. After normal rats and RSV pneumonia model rats were orally administered with Maxing Shigan decoction, the blood was collected from retinal vein plexus of different time points. Specifically, tetrahydropalmatine was taken as internal standard for determining ephedrine, while chloramphenicol was taken as internal standard for determining other components. After plasma samples were pre-treated as the above, the supernatant was dried with nitrogen blowing concentrator and then redissolved with methylalcohol. The chromatography was eluted with mobile phase consisted of acetonitrile and 0.1% formic acid solution in a gradient manner. ESI sources were adopted to scan ingredients in ephedra in a positive ion scanning mode and other ingredientsin a negative ion scanning mode. The multiple-reaction monitoring (MRM) method was developed the plasma concentration of each active component. The pharmacokinetic parameters of each group were calculated by using Win-Nonlin 4.1 software and put into the statistical analysis. The result showed the plasma concentration of the eight active ingredients, i.e., liquiritin, glycyrrhizin, glycyrrhetinic acid, amygdalin, amygdalin prunasin, ephedrine, pseudoephedrine and methylephedrine within the ranges of 1.04-1040, 1.04-1040, 0.89-445, 1.05-4200, 1.25-2490, 0.3-480, 0.3-480, 0.3-480 microg x L(-1), with a good linearity and satisfactory precision, recovery and stability in the above ingredients. After modeling, except for glycyrrhetinic acid whose pharmacokinetic parameters were lacked due to the data missing, all of the rest components showed significant higher Cmax, AUC(0-1) and lower clearance rate (CL

  16. [Optimization of high-cell-density fermentation process for S-adenosyl-L-methionine production].

    PubMed

    Wang, Jiepeng; Han, Jinjun; Li, Xiaonan; Liu, Peiyi; Tan, Tianwei

    2009-04-01

    Poor stability existed in the anaphase of the high-cell-density fermentation of Saccharomyces crevisiae for S-adenosyl-L-methionine (SAM) production in 5 L fermentor. To improve the fermentation stability, we studied the addition of diammonium hydrogen phosphate, sodium glutamate and adenosine disodium triphosphate into glucose feeding solution. Study of four fed-batch cultures showed that, after 34 h fermentation, when dry cell weight reached 100 g/L, the addition of 50 g pre-L-methionine and glucose feeding with 10 g/L adenosine disodium triphosphate was optimal for SAM production. Under this condition, after 65.7 h fermentation, both the dry cell weight and the yield of SAM reached the maximum, 180 g/L and 17.1 g/L respectively. PMID:19637627

  17. Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.

    1988-01-01

    Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation-induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia.

  18. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2009-10-01

    [Methoxy-11c]PD-153035; Afamelanotide, Agalsidase beta, Alemtuzumab, Alkaline phosphatase, Amlodipine, Anecortave acetate, Apixaban, Aripiprazole, Atomoxetine hydrochloride; Bevacizumab, Bortezomib, Bosentan, Botulinum toxin type B, Brimonidine tartrate/timolol maleate, Brivudine; Canakinumab, Cetuximab, Chlorotoxin, Cinaciguat; Dapagliflozin, Decitabine, Duloxetine hydrochloride; Elagolix sodium, Eplerenone, Eritoran tetrasodium, Escitalopram oxalate, Etoricoxib, Ezetimibe; Fospropofol disodium; G-207, Gabapentin enacarbil, Gefitinib, Golimumab; Human plasmin; Inotuzumab ozogamicin, Insulin glargine, Insulin glulisine, Istaroxime, Ixabepilone; KLH; Levodopa/carbidopa/entacapone; Miglustat, Mitumprotimut-T, MP-470; Oblimersen sodium, Olmesartan medoxomil; P53-SLP, PAN-811, Patupilone, Pazopanib hydrochloride, PC-515, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Pemetrexed disodium, Plitidepsin, Pregabalin; Rasagiline mesilate, Rotigotine; SCH-697243, Sirolimus-eluting stent, Sumatriptan succinate/naproxen sodium, Sunitinib malate; Tadalafil, Tapentadol hydrochloride, TMC-207; V-211, Valganciclovir hydrochloride; Zolpidem tartrate.

  19. Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.

    1988-01-01

    Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration of disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia. 34 references, 5 figures, 2 tables.

  20. Proteolytic activity of beef luncheon fungi as affected by incorporation of some food preservatives.

    PubMed

    Saleem, A; El-Said, A H M

    2009-12-01

    Screening of thirty-one fungal isolates (representing 16 genera, 28 species and 3 varieties) collected from beef luncheon meat for their abilities to produce protease enzyme revealed that eleven isolates (35.48%) exhibited high protease production. However, fifteen isolates (48.39%) had moderate ability and 5 isolates (16.13%) were low producers. Aspergillus flavus, Gibberella fujikuroi and Penicillium chrysogenum were the most active producers of protease. The incorporation of five chemical substances used as food preservatives (disodium phosphate, sodium benzoate, citric acid, potassium sorbate and sodium citrate) individually in the culture medium for protease production exhibited depressive effect on protease production as well as on mycelial growth of Aspergillus flavus, Gibberella fujikuroi and Penicillium chrysogenum , except in few cases the mycelial growth of A. flavus and G. fujikuroi was increased by the lowest concentration (100 ppm) of sodium benzoate, citric acid and disodium phosphate.

  1. Optimization of nutrients for gellan gum production by Sphingomonas paucimobilis ATCC-31461 in molasses based medium using response surface methodology.

    PubMed

    Banik, R M; Santhiagu, A; Upadhyay, S N

    2007-03-01

    A molasses based medium for the production of gellan by Sphingomonas paucimobilis ATCC-31461 was developed. Placket-Burman design criterion was applied to study the effect of various nutrient supplements on gellan production using molasses. Among the 20 variables tested, molasses, tryptone, casaminoacid, disodium hydrogen orthophosphate and manganese chloride showed significant effect on gellan production. A central composite design was applied to determine the optimum concentrations of the significant variables obtained from Placket-Burman design. Most suitable medium composition for production of gellan was (g/l): molasses-112.5; tryptone-1; casaminoacid-1; disodium hydrogen orthophosphate-1; manganese chloride-0.947 and the optimum gellan production was 13.814 g/l.

  2. Role of neurotensin in radiation-induced hypothermia in rats

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A.; Harris, A.H. )

    1991-05-01

    The role of neurotensin in radiation-induced hypothermia was examined. Intracerebroventricular (ICV) administration of neurotensin produced dose-dependent hypothermia. Histamine appears to mediate neurotensin-induced hypothermia because the mast cell stabilizer disodium cromoglycate and antihistamines blocked the hypothermic effects of neurotensin. An ICV pretreatment with neurotensin antibody attenuated neurotensin-induced hypothermia, but did not attenuate radiation-induced hypothermia, suggesting that radiation-induced hypothermia was not mediated by neurotensin.

  3. 21 CFR 177.1655 - Polysulfone resins.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Polysulfone resins. 177.1655 Section 177.1655 Food... (CAS Reg. No. 25154-01-2) consisting of basic resins produced when the disodium salt of 4,4...; or (2) 1,1′-Sulfonylbis polymer with 4,4′-(1-methylethylidene)bis (minimum 92 percent) and...

  4. 21 CFR 74.1707a - Ext. D&C Yellow No. 7.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1707a Ext. D&C Yellow No. 7. (a) Identity. (1) The color additive Ext. D&C Yellow No. 7 is principally the disodium salt of 8-hydroxy-5,7-di-nitro-2-naphthalenesulfonic acid. (2) Color additive mixtures for drug use made with Ext. D&C Yellow No. 7 may contain...

  5. Syntheses, structures, thermal stabilities and luminescence of two new lead sulfonates with phosphonate, carboxylate and pyridine

    NASA Astrophysics Data System (ADS)

    Fu, Ruibiao; Hu, Shengmin; Wu, Xintao

    2014-05-01

    Hydrothermal reactions of Pb2+ ion with disodium 4,4'-bis(2-sulfonatostyryl)biphenyl (Na2L1), 4-pyridyl-CH2N(CH2COOH)(CH2PO3 H2) (H3L2) and 4,4'-bipyridine (4,4'-bipy) afforded two new lead sulfonates, namely, [Pb4(L1)2(HL2)2(H2O)

  6. 21 CFR 74.1710 - D&C Yellow No. 10.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... additive D&C Yellow No. 10 is a mixture of the sodium salts of the mono- and disulfonic acids of 2-(2-quinolinyl)-1H-indene-1,3 (2H)-dione consisting principally of the sodium salts of 2-(2,3-dihydro-1,3-dioxo...-quinolinesulfonic acid with lesser amounts of the disodium salts of the disulfonic acids of...

  7. 21 CFR 74.1707a - Ext. D&C Yellow No. 7.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... color additive Ext. D&C Yellow No. 7 is principally the disodium salt of 8-hydroxy-5,7-di-nitro-2-naphthalenesulfonic acid. (2) Color additive mixtures for drug use made with Ext. D&C Yellow No. 7 may contain only those diluents that are suitable and that are listed in part 73 of this chapter as safe for use in...

  8. 21 CFR 74.1710 - D&C Yellow No. 10.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... additive D&C Yellow No. 10 is a mixture of the sodium salts of the mono- and disulfonic acids of 2-(2-quinolinyl)-1H-indene-1,3 (2H)-dione consisting principally of the sodium salts of 2-(2,3-dihydro-1,3-dioxo...-quinolinesulfonic acid with lesser amounts of the disodium salts of the disulfonic acids of...

  9. Self-Healing and Moldable Metallogels as the Recyclable Materials for Selective Dye Adsorption and Separation.

    PubMed

    Karan, Chandan Kumar; Bhattacharjee, Manish

    2016-03-01

    Four multiresponsive and self-sustaining metallogels were synthesized by the reaction of the disodium salt of the ligand carboxymethyl-(3,5-di-tert-butyl-2-hydroxy-benzyl)amino acetic acid with Cd(II) and Zn(II) halides, which were found to show excellent selectivity for dye adsorption and separation, and one of the gels shows a rare self-healing property. PMID:26854670

  10. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false FD&C Red No. 4. 74.1304 Section 74.1304 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1304 FD&C Red No. 4. (a) Identity. (1) The color additive FD&C Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

  11. 21 CFR 74.1322 - D&C Red No. 22.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Red No. 22. 74.1322 Section 74.1322 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1322 D&C Red No. 22. (a) Identity. (1) The color additive D&C Red No. 22 is principally the disodium salt of 2′,4′,5′7′-tetrabromofluorescein (CAS Reg. No....

  12. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  13. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  14. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  15. Effects of phosphate addition on methane fermentation in the batch and upflow anaerobic sludge blanket (UASB) reactors.

    PubMed

    Suzuki, Sho; Shintani, Masaki; Sanchez, Zoe Kuizon; Kimura, Kohei; Numata, Mitsuru; Yamazoe, Atsushi; Kimbara, Kazuhide

    2015-12-01

    Ammonia inhibition of methane fermentation is one of the leading causes of failure of anaerobic digestion reactors. In a batch anaerobic digestion reactor with 429 mM NH3-N/L of ammonia, the addition of 25 mM phosphate resulted in an increase in methane production rate. Similar results were obtained with the addition of disodium phosphate in continuous anaerobic digestion using an upflow anaerobic sludge blanket (UASB) reactor. While methane content and production rate decreased in the presence of more than 143 mM NH3-N/L of ammonium chloride in UASB, the addition of 5 mM disodium phosphate suppressed ammonia inhibition at 214 mM NH3-N/L of ammonium chloride. The addition prevented acetate/propionate accumulation, which might be one of the effects of the phosphate on the ammonia inhibition. The effects on the microbial community in the UASB reactor was also assessed, which was composed of Bacteria involved in hydrolysis, acidogenesis, acetogenesis, and dehydrogenation, as well as Archaea carrying out methanogenesis. The change in the microbial community was observed by ammonia inhibition and the addition of phosphate. The change indicates that the suppression of ammonia inhibition by disodium phosphate addition could stimulate the activity of methanogens, reduce shift in bacterial community, and enhance hydrogen-producing bacteria. The addition of phosphate will be an important treatment for future studies of methane fermentation.

  16. Safety and Efficacy of Gadoxetate Disodium–Enhanced Liver MRI in Pediatric Patients Aged >2 Months to <18 Years—Results of a Retrospective, Multicenter Study

    PubMed Central

    Geller, James; Kasahara, Mureo; Martinez, Mercedes; Soresina, Annarosa; Kashanian, Fran; Endrikat, Jan

    2016-01-01

    PURPOSE To assess the safety and efficacy of gadoxetate disodium–enhanced liver MR imaging in pediatric patients. MATERIAL AND METHODS Retrospective, multicenter study including pediatric patients aged >2 months to <18 years who underwent contrast-enhanced liver MRI due to focal liver lesions. A single intravenous bolus injection of 0.025 to 0.05 mmol/kg body weight of gadoxetate disodium was administered. Adverse events (AEs) up to 24 hours after injection were recorded and a one-year follow-up was conducted for all serious and unexpected AEs. Efficacy was defined based on the additional diagnostic information obtained from the combined (pre- and postcontrast) image sets as compared with the precontrast image sets by blinded reading. RESULTS A total of 52 patients for safety and 51 patients for efficacy analyses were evaluated. Twenty-two patients (42.3%) reported a total of 51 serious AEs (SAEs) and one AE after one year. No SAE or AE was related to gadoxetate disodium injection. Gadoxetate disodium–related effects on vital signs were not seen. Additional diagnostic information was obtained for 86.3% of patients. The three most improved efficacy variables were lesion-to-background contrast, lesion characterization, and improved border delineation in 78.4%, 76.5%, and 70.6% of patients, respectively. CONCLUSION Gadoxetate disodium in pediatric patients did not raise any clinically significant safety concern. Contrast enhancement provided additional clinically relevant information. PMID:27478381

  17. FTIR and {sup 31}P-NMR spectroscopic analyses of surface species in phosphate-catalyzed lactic acid conversion

    SciTech Connect

    Gunter, G.C.; Tam, M.S.; Miller, D.J.

    1996-11-01

    The surface species present on silica/alumina-supported sodium phosphates, active catalysts for the conversion of lactic acid to acrylic acid and 2,3-pentanedione, are examined by pre- and postreaction MAS {sup 31}P-NMR and FTIR spectroscopies. Species present following lactic acid conversion are identified by transmission FTIR of phosphates supported on silicon disks (as a model catalyst system) and verified by {sup 31}P-NMR and diffuse reflectance IR spectroscopy of actual catalysts used in reaction. Monosodium phosphate (NaH{sub 2}PO{sub 4}) condenses to a mixture of sodium polyphosphate (NaPO{sub 3}){sub n} and sodium trimetaphosphate (Na{sub 3}P{sub 3}O{sub 9}), which exhibit little catalytic activity for converting lactic acid to desired products. Disodium phosphate (Na{sub 2}HPO{sub 4}) condenses to tetrasodium pyrophosphate (Na{sub 4}P{sub 2}O{sub 7}), and proton transfer from lactic acid to pyrophosphate results in the formation of sodium lactate. Trisodium phosphate (Na{sub 3}PO{sub 4}) accepts a proton from lactic acid to form sodium lactate and disodium phosphate, which condenses to pyrophosphate. The presence of pyrophosphate and sodium lactate on supported disodium and trisodium phosphates explains their similar catalytic properties; the larger quantity of sodium lactate present on trisodium phosphate leads to higher conversions at lower temperatures. 40 refs., 14 figs., 2 tabs.

  18. Feasibility of using saturated solar ponds for brine unmixing. Final report

    SciTech Connect

    Not Available

    1980-09-30

    The overall objective of this study was to investigate in the laboratory the feasibility of using saturated solar ponds for unmixing a brine of intermediate concentration into dilute and concentrated brine streams for salinity gradient energy conversion systems. This objective was accomplished by conducting experiments on laboratory saturated ponds using borax, potassium perchlorate, potassium nitrate, disodium phosphate and potassium alum. Results from ponds using borax, potassium nitrate and disodium phosphate conclusively demonstrated that saturated solar ponds can self-generate and self-maintain a stable density gradient. Moreover, these ponds reestablished stable density profiles after the ponds were externally mixed. Based on preliminary results, the residence time for unmixing of a brine of intermediate concentration into dilute and concentrated brine streams varies from a few days for the borax pond to about two weeks for the disodium phosphate pond, depending upon the characteristics of the individual saturated solution. Because of only a very small increase in the density of saturated solutions from 25/sup 0/C to 90/sup 0/C, the potassium perchlorate pond could not establish a stable density stratification.

  19. Ursolic acid from Plantago major, a selective inhibitor of cyclooxygenase-2 catalyzed prostaglandin biosynthesis.

    PubMed

    Ringbom, T; Segura, L; Noreen, Y; Perera, P; Bohlin, L

    1998-10-01

    A hexane extract of Plantago major was investigated by bioactivity-directed fractionation, using an in vitro cyclooxygenase-2 (COX-2) catalyzed prostaglandin biosynthesis inhibition assay, and resulted in the isolation of ursolic acid (1). This triterpenoid showed a significant COX-2 inhibitory effect, directly on the enzyme activity, with an IC50 value of 130 microM and a COX-2/COX-1 selectivity ratio of 0.6. The structural isomer oleanolic acid (2) was found to be less active than 1, with an IC50 value of 295 microM, but showed a similar selectivity ratio (0.8). Furthermore, no significant inhibition on COX-2 or COX-1 was observed by the triterpenoid, 18beta-glycyrrhetinic acid (3). The direct inhibitory effect of 1 and 2 on COX-2 catalyzed prostaglandin biosynthesis increased with preincubation, indicating a time-dependent inhibition, while the effect on COX-1 was found to be independent of preincubation time.

  20. [Anti-virus research of triterpenoids in licorice].

    PubMed

    Pu, Jie-Ying; He, Li; Wu, Si-Yu; Zhang, Ping; Huang, Xi

    2013-11-01

    Licorice is a leguminous plant of glycyrrhiza. It is a traditional Chinese herbal medicine. Triterpenoid is one of the mainly active components of licorice. In recent years, the broad-spectrum antiviral activity of many triterpenoids in licorice was confirmed, and these findings have become a hot spot of antiviral immunity. The triterpenoids of licorice has the potential to become a novel broad-spectrum antiviral medicine and will be widely used in the clinical treatment. This review provided a summary of the recent anti-virus research progress on several triterpenoids in licorice, such as glycyrrhizic acid, glycyrrhizin, glycyrrhetinic acid and its derivatives. The antiviral roles of triterpenoids in licorice against herpes virus, HIV, hepatitis virus, SARS coronavirus and influenza virus were briefly summarized.

  1. Phenotypic transformation of smooth muscle cells from porcine coronary arteries is associated with connexin 43

    PubMed Central

    ZHANG, XUMIN; WANG, XIAODONG; ZHOU, XIAOHUI; MA, XIAOYE; YAO, YIAN; LIU, XUEBO

    2016-01-01

    The current study aimed to investigate the relevance of the gap junction protein connexin Cx43 in coronary artery smooth muscle cell (SMC) heterogeneity and coronary artery restenosis. SMCs were isolated from the coronary artery of 3-month-old pigs using enzymatic digestion. Two distinct SMC populations were isolated: Rhomboid (R) and spindle-shaped (S) cells. S-SMCs exhibited relatively lower rates of proliferation, exhibiting a classic ''hills-and valleys'' growth pattern; R-SMCs displayed increased proliferation rates, growing as mono- or multi-layers. Immunofluorescent staining, polymerase chain reaction and western blotting were used to assess the expression of Cx40 and Cx43 in SMCs. For further evaluation, cultured SMCs were treated with 10 ng/ml platelet-derived growth factor (PDGF)-BB with or without the gap junction blocker 18α-glycyrrhetinic acid. Stent-induced restenosis was assessed in vivo. Different expression patterns were observed for Cx40 and Cx43 in R- and S-SMCs. Cx40 was the most abundant Cx in S-SMCs, whereas CX43 was identified at relatively higher levels than Cx40 in R-SMCs. Notably, PDGF-BB converted S-SMCs to R-SMCs, with increased Cx43 expression, while 18α-glycyrrhetinic acid inhibited the PDGF-BB-induced phenotypic alterations in S-SMCs. Additionally, restenosis was confirmed in pigs 1-month subsequent to stent placement. R-SMCs were the major cell population isolated from stent-induced restenosis artery tissues, and exhibited markedly increased Cx43 expression, in accordance with the in vitro data described above. In conclusion, the phenotypic transformation of coronary artery SMCs is closely associated with Cx43, which is involved in restenosis. These observations provide a basis for the use of Cx43 as a novel target in restenosis prevention. PMID:27175888

  2. [The interactions between natural products and OATP1B1].

    PubMed

    Shi, Mei-zhi; Liu, Yu; Bian, Jia-lin; Jin, Meng; Gui, Chun-shan

    2015-07-01

    Organic anion transporting polypeptide 1B1 (OATP1B1) is an important liver-specific uptake transporter, which mediates transport of numerous endogenous substances and drugs from blood into hepatocytes. To identify and investigate potential modulators of OATP1B1 from natural products, the effect of 21 frequently used natural compounds and extracts on OATP1B1-mediated fluorescein methotrexate transport was studied by using Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) in 96-well plates. This method could be used for the screening of large compound libraries. Our studies showed that some flavonoids (e.g., quercetin, quercitrin, rutin, chrysanthemum flavonoids and mulberrin) and triterpenoids (e.g., glycyrrhetinic acid and glycyrrhizic acid) were inhibitors of OATP1B1 with IC50 values less than 16 µmol · L(-1). The IC50 value of glycyrrhetinic acid on OATP1B1 was comparable to its blood concentration in clinics, indicating an OATPlB1-mediated drug-drug interaction could occur. Structure-activity relationship analysis showed that flavonoids had much higher inhibitory activity than their glycosides. Furthermore, the type and length of saccharides had a significant effect on their activity. In addition, we used OATP1B1 substrates fluvastatin and rosuvastatin as probe drugs to investigate the substrate-dependent effect of several natural compounds on the function of OATP1B1 in vitro. Our results demonstrated that the effect of these natural products on the function of OATPlB1 was substrate-dependent. In summary, this study would be conducive to predicting and avoiding potential OATP1B1-mediated drug-drug and drug-food interactions and thus provide the experimental basis and guidance for rational drug use. PMID:26552146

  3. GnRH Episodic Secretion Is Altered by Pharmacological Blockade of Gap Junctions: Possible Involvement of Glial Cells.

    PubMed

    Pinet-Charvet, Caroline; Geller, Sarah; Desroziers, Elodie; Ottogalli, Monique; Lomet, Didier; Georgelin, Christine; Tillet, Yves; Franceschini, Isabelle; Vaudin, Pascal; Duittoz, Anne

    2016-01-01

    Episodic release of GnRH is essential for reproductive function. In vitro studies have established that this episodic release is an endogenous property of GnRH neurons and that GnRH secretory pulses are associated with synchronization of GnRH neuron activity. The cellular mechanisms by which GnRH neurons synchronize remain largely unknown. There is no clear evidence of physical coupling of GnRH neurons through gap junctions to explain episodic synchronization. However, coupling of glial cells through gap junctions has been shown to regulate neuron activity in their microenvironment. The present study investigated whether glial cell communication through gap junctions plays a role in GnRH neuron activity and secretion in the mouse. Our findings show that Glial Fibrillary Acidic Protein-expressing glial cells located in the median eminence in close vicinity to GnRH fibers expressed Gja1 encoding connexin-43. To study the impact of glial-gap junction coupling on GnRH neuron activity, an in vitro model of primary cultures from mouse embryo nasal placodes was used. In this model, GnRH neurons possess a glial microenvironment and were able to release GnRH in an episodic manner. Our findings show that in vitro glial cells forming the microenvironment of GnRH neurons expressed connexin-43 and displayed functional gap junctions. Pharmacological blockade of the gap junctions with 50 μM 18-α-glycyrrhetinic acid decreased GnRH secretion by reducing pulse frequency and amplitude, suppressed neuronal synchronization and drastically reduced spontaneous electrical activity, all these effects were reversed upon 18-α-glycyrrhetinic acid washout.

  4. 3-Monoglucuronyl glycyrrhretinic acid is a possible marker compound related to licorice-induced pseudoaldosteronism.

    PubMed

    Makino, Toshiaki

    2014-01-01

    One of the most common adverse effects of traditional Japanese kampo and traditional Chinese medicine is pseudoaldosteronism caused by licorice. In this review, the authors describe the mechanisms of licorice-induced pseudoaldosteronism by the pharmacokinetics of chemical constituents and its metabolites containing licorice. Glycyrrhizin (GL), the main constituent of licorice, is absorbed as glycyrrhetinic acid (GA), which is a metabolite of GL produced by enterobacteria before its release into the circulation. Circulating GA is metabolized in the liver to become 3-monoglucuronyl-glycyrrhetinic acid (3MGA), which is excreted into the bile via multidrug resistance protein 2 (Mrp2). If Mrp2 function is damaged for some reason, 3MGA is secreted from the liver into the circulation, and excreted into the urine via organic anion transporters expressed at the basolateral side of tubular epithelial cells. Circulating GA cannot be excreted into the urine since GA binds highly to serum albumin and thus does not pass through glomerular filtration and is not a substrate of transporters expressed on tubular epithelial cells. Licorice-induced pseudoaldosteronism develops due to the inhibition of type 2 11β-hydrosteroid dehydrogenase (11β-HSD2) which results in the accumulation of cortisol in tubular epithelial cells that activate mineral corticoid receptors to stimulate the excretion of potassium that results in hypokalemia. GA, unlike 3MGA, cannot pass through tubular epithelial cells and cannot inhibit the enzyme in the cells. Therefore, 3MGA may be a genuine causative agent for licorice-induced pseudoaldosteronism. When licorice is used, 3MGA in plasma or urine could function as a marker compound to prevent the adverse effects.

  5. I. Enabling Single-Chain Surfactants to Form Vesicles by Nonamphiphilic Liquid Crystals in Water II. Controlling Attachment and Ligand-Mediated Adherence of Candida albicans on Monolayers

    NASA Astrophysics Data System (ADS)

    Varghese, Nisha

    This dissertation describes a fundamental study of weak noncovalent interactions and surface forces that exist at the interfaces of various interacting moieties (small molecules or microbes), and its relevance to colloidal and material chemistry. Chapter 1 presents an emulsion system that enables single-chain anionic or nonionic surfactants to sequester and encapsulate certain water-soluble organic salts, leading to the formation of vesicles in water. The water-soluble organic salt in the system comprises of disodium cromoglycate crystals that are emulsified by surfactants in water to form stable liquid crystal droplets. The work provides an exception to the rule of geometric packing factor that dictates formation of micelles by the surfactants in water. Chapter 2 shows that the odd or even number of carbon atoms present in the aliphatic chain of surfactants affect the ability of surfactants to emulsify aqueous-based liquid crystals of disodium cromoglycate. Such an odd-even effect is frequently observed for solid state properties like melting point, heat of fusion and refractive index but is rarely observed for molecules present in solution. When mixed in water, anionic single-chain surfactants with odd number of carbon atoms emulsifies disodium cromoglycate to form liquid crystal droplets, while surfactants with even number of carbon atoms fail to emulsify disodium cromoglycate. Chapter 3 Bolaamphiphiles usually form vesicles only in extreme conditions or in the presence of surfactants. Here, we explore the co-assembly system of synthesized bolaamphiphiles and disodium cromoglycate in water. The combination of the self-assembly forces of the bolaamphiphile and self-associating property of disodium cromoglycate liquid crystals act together at the interface form a unique microemulsion of liquid crystal droplets of disodium cromoglycate embedded in liquid crystal phase. Chapter 4 describes a key event (adhesion) that precedes infections caused by Candida albicans

  6. Calorimetric and Diffractometric Evidence for the Sequential Crystallization of Buffer Components and the Consequential pH Swing in Frozen Solutions

    SciTech Connect

    Sundaramurthi, Prakash; Shalaev, Evgenyi; Suryanarayanan, Raj

    2010-06-22

    Sequential crystallization of succinate buffer components in the frozen solution has been studied by differential scanning calorimetry and X-ray diffractometry (both laboratory and synchrotron sources). The consequential pH shifts were monitored using a low-temperature electrode. When a solution buffered to pH < pK{sub a2} was cooled from room temperature (RT), the freeze-concentrate pH first increased and then decreased. This was attributed to the sequential crystallization of succinic acid, monosodium succinate, and finally disodium succinate. When buffered to pH > pK{sub a2}, the freeze-concentrate pH first decreased and then increased due to the sequential crystallization of the basic (disodium succinate) followed by the acidic (monosodium succinate and succinic acid) buffer components. XRD provided direct evidence of the crystallization events in the frozen buffer solutions, including the formation of disodium succinate hexahydrate [Na{sub 2}(CH{sub 2}COO){sub 2} {center_dot} 6H{sub 2}O]. When the frozen solution was warmed in a differential scanning calorimeter, multiple endotherms attributable to the melting of buffer components and ice were observed. When the frozen solutions were dried under reduced pressure, ice sublimation was followed by dehydration of the crystalline hexahydrate to a poorly crystalline anhydrate. However, crystalline succinic acid and monosodium succinate were retained in the final lyophiles. The pH and the buffer salt concentration of the prelyo solution influenced the crystalline salt content in the final lyophile. The direction and magnitude of the pH shift in the frozen solution depended on both the initial pH and the buffer concentration. In light of the pH-sensitive nature of a significant fraction of pharmaceuticals (especially proteins), extreme care is needed in both the buffer selection and its concentration.

  7. [Quantitative determination of penicillins by iodometry using potassium hydrogen peroxymonosulfate].

    PubMed

    Blazhevskiĭ, N E; Karpova, S P; Kabachyĭ, V I

    2013-01-01

    The kinetics and stoichiometry of S-oxidation of semisynthetic penicillins (amoxicillin trihydrate, ampicillin trihydrate, sodium salt of oxacillin and ticarcillin disodium salt) by potassium hydrogen peroxymonosulfate in aqueous solutions at pH 3-6 was studied by iodometric titration: 1 mol of KNSO5 per 1 mol of penicillin, the quantitative interaction is achieved in 1 min (time of observation). A unified method was developed and the possibility of quantification of penicillins by the iodometric method using potassium hydrogen peroxymonosulfate as an analytical reagent was shown.

  8. Kinetic investigation of the action of hyaluronidase on hyaluronan using the Morgan-Elson and neocuproine assays.

    PubMed

    Vercruysse, K P; Lauwers, A R; Demeester, J M

    1995-08-15

    In this paper we describe kinetic investigations of the action of testicular hyaluronidase on hyaluronan. We have compared the use of two spectrophotometric assays, the first based on the Morgan-Elson reaction and the second on the neocuproine reaction. With the neocuproine reaction Km was found to be 0.46 mg/ml and Vmax to be 126 nmol l-1 s-1. Because of a low sensitivity and the production of interfering precipitates, the Morgan-Elson assay cannot be used for kinetic investigation of the enzyme. Furthermore this assay is prone to interference from compounds such as disodium cromoglycate, (+)-catechine, penicillamine, CaCl2 and acetate buffer.

  9. AFRRI (Armed Forces Radiobiology Research Institute) reports, January, February and March 1988. Technical report

    SciTech Connect

    Not Available

    1988-05-01

    A possible mechanism by which disodium cromoglycate (DSCG) prevents a decrease in regional cerebral blood flow but not hypotension in primates following whole body gamma irradiation was studied. Several studies have implicated superoxide radicals in intestinal and cerebral vascular disorders following ischemia and ionizing radiation, respectively, The superoxide radical is formed during radiolysis in the reaction between hydrated electrons and dissolved oxygen. For this reason, the efficiency of DSCG to scavenge hydrated electrons and possibly prevent the formation of the superoxide radical was studied. The results show that DSCG is an efficient hydrated-electrons scavenger and may effectively compete with oxygen for hydrated electrons preventing the radiolytic formation of the superoxide radicals.

  10. Automatic photometric titrations of calcium and magnesium in carbonate rocks

    USGS Publications Warehouse

    Shapiro, L.; Brannock, W.W.

    1955-01-01

    Rapid nonsubjective methods have been developed for the determination of calcium and magnesium in carbonate rocks. From a single solution of the sample, calcium is titrated directly, and magnesium is titrated after a rapid removal of R2O3 and precipitation of calcium as the tungstate. A concentrated and a dilute solution of disodium ethylenediamine tetraacetate are used as titrants. The concentrated solution is added almost to the end point, then the weak solution is added in an automatic titrator to determine the end point precisely.

  11. Quantitating the association of charged molecules with ionic micelles

    NASA Astrophysics Data System (ADS)

    Stevenson, Sarah A.; Blanchard, G. J.

    2007-05-01

    We have studied micelles comprised of cationic (CTAB) and anionic (SDS) surfactants through the interactions of solution phase anionic disodium fluorescein (DSF) and cationic rhodamine 110 (R110) dyes with perylene sequestered within the micelles. Fluorescence lifetime measurements monitor energy transfer between the nonpolar optical donor within the micelle and ionic probes in the surrounding solution. The efficiency of this process is mediated by the extent to which the ionic dyes interact with the micelle palisade layer, and our fluorescence lifetime data allow us to determine the association constants for acceptor-micelle interactions.

  12. Polyimides prepared from perfluoroisopropylidene diamine

    NASA Technical Reports Server (NTRS)

    Jones, Robert J. (Inventor); O'Rell, Michael K. (Inventor); Hom, Jim M. (Inventor)

    1978-01-01

    This invention relates to a novel aromatic diamine and more particularly to the use of said diamine for the preparation of thermally stable high-molecular weight polymers including, for example, polyamides, polyamideimides, polyimides, and the like. This diamine is obtained by reacting a stoichometric amount of a disodium salt of 2,2-bis(4-hydroxyphenyl) hexafluoropropane with 4-chloronitrobenzene to obtain an intermediate, 2,2-bis[4-(4-nitrophenoxy)phenyl] hexafluoropropane, which is reduced to the corresponding 2,2-bis[4-(4-aminophenoxy)phenyl] hexafluoropropane.

  13. Total selenium concentration in various waters of Turkey.

    PubMed

    Yanardağ, R; Orak, H

    2001-02-01

    The total selenium levels of 335 water samples of Turkey were determined by a spectrofluorometric method. The samples were digested in nitric-perchloric acid mixture, potential interferences were masked with disodium EDTA-HONH2.HCl and selenium was complexed with freshly prepared 2,3-diaminonaphthalene solution and estimated spectrofluorometrically after extraction in cyclohexane. The selenium content of various waters (rain, tap, mineral, sea, lake, river, bottled drinking waters and collected drinking waters from 42 cities in Turkey) were determined. The selenium levels were compared with the literature data from different countries.

  14. Syntheses, structures, thermal stabilities and luminescence of two new lead sulfonates with phosphonate, carboxylate and pyridine

    SciTech Connect

    Fu, Ruibiao Hu, Shengmin; Wu, Xintao

    2014-05-01

    Hydrothermal reactions of Pb{sup 2+} ion with disodium 4,4'-bis(2-sulfonatostyryl)biphenyl (Na{sub 2}L1), 4-pyridyl-CH{sub 2}N(CH{sub 2}COOH)(CH{sub 2}PO{sub 3} H{sub 2}) (H{sub 3}L2) and 4,4'-bipyridine (4,4'-bipy) afforded two new lead sulfonates, namely, [Pb{sub 4}(L1){sub 2}(HL2){sub 2}(H{sub 2}O)

  15. Gadolinium contrast agent selection and optimal use for body MR imaging.

    PubMed

    Guglielmo, Flavius F; Mitchell, Donald G; Gupta, Shiva

    2014-07-01

    Proper selection of a gadolinium-based contrast agent (GBCA) for body magnetic resonance imaging (MRI) cases requires understanding the indication for the MRI exam, the key features of the different GBCAs, and the effect that the GBCA has on the selected imaging protocol. The different categories of GBCAs require timing optimization on postcontrast sequences and adjusting imaging parameters to obtain the highest T1 contrast. Gadoxetate disodium has many advantages when evaluating liver lesions, although there are caveats and limitations that need to be understood. Gadobenate dimeglumine, a high-relaxivity GBCA, can be used for indications when stronger T1 relaxivity is needed.

  16. Membrane-facilitated bioproduction of 3-methylcatechol in an octanol/water two-phase system.

    PubMed

    Hüsken, Leonie E; Oomes, Mirjam; Schroën, Karin; Tramper, Johannes; de Bont, Jan A M; Beeftink, Rik

    2002-07-01

    Bioproduction of 3-methylcatechol from toluene by Pseudomonas putida MC2 was studied in the presence of an additional 1-octanol phase. This solvent was used to supply the substrate and extract the product, in order to keep the aqueous concentrations low. A hollow-fibre membrane kept the octanol and aqueous phase separated to prevent phase toxicity towards the bacterium. Volumetric production rates increased approximately 40% as compared to two-phase 3-methylcatechol production with direct phase contact. Preliminary investigations on downstream processing of 3-methylcatechol showed that 1 M of sodium hydroxide selectively extracted the disodium salt of 3-methylcatechol into an aqueous phase. PMID:12044556

  17. Crystal structure of Na2HfSi2O7 by Rietveld refinement

    PubMed Central

    Massoni, Nicolas; Chevreux, Pierrick

    2016-01-01

    The structure of triclinic disodium hafnium disilicate, Na2HfSi2O7, has been determined by laboratory powder X-ray diffraction and refined by the Rietveld refinement. The structure is a framework made of alternate layers of HfO6 octa­hedra and SiO4 tetra­hedra linked by common O atoms. Sodium atoms are located in the voids of the framework, aligned into tunnels along the [010] direction. Na2HfSi2O7 is isostructural with the parakeldyshite Na2ZrSi2O7 phase. PMID:27746936

  18. Spectroscopic characterization of SC-NTR: a subsidiary dye of allura red AC dye (FD&C red no. 40).

    PubMed

    Takeda, Y; Goda, Y; Noguchi, H; Yamada, T; Yoshihira, K; Takeda, M

    1994-01-01

    A major subsidiary dye in US certified Allura Red AC dye (FD&C Red No. 40) has been isolated by preparative high performance liquid chromatography. The paper chromatographic properties of the isolated dye indicate that it is the dye designated as SC-NTR in a previous paper (Marmion 1971). Spectroscopic analysis of the isolated dye is consistent with the disodium salt of 6-hydroxy-5-(2-methoxy-5-methyl-3-sulphophenylazo)-2-naphthalen esulphonic acid, which is an azo-coupling product between the meta-isomer of cresidine-p-sulphonic acid (CSA) and Schaeffer's salt (SS).

  19. Fluid Shear-Induced ATP Secretion Mediates Prostaglandin Release in MC3T3-E1 Osteoblasts

    PubMed Central

    Genetos, Damian C.; Geist, Derik J.; Dawei, Liu; Donahue, Henry J.; Duncan, Randall L.

    2010-01-01

    release, whereas inhibition of gap hemichannels with either 18α-glycyrrhetinic acid or 18β-glycyrrhetinic acid did not. Degradation of extracellular ATP with apyrase prevented shear-induced increases in PGE2 release. These data suggest a time line of mechanotransduction wherein fluid shear activates L-VSCC's to promote Ca2+ entry that, in turn, stimulates vesicular ATP release. Further, these data suggest that P2 receptor activation by secreted ATP mediates flow-induced prostaglandin release. PMID:15619668

  20. Purification of fallout-contaminated water studied

    SciTech Connect

    Lu Deyuan; Cai, X.; Li, M.; Liu, T.

    1983-04-30

    This article presents data from an experiment conducted in China in which the ability of certain purification materials and drinking water decontaminants were tested with water polluted by fallout from nuclear explosions. It is explained that the explosion of nuclear weapons or the dissemination of radioactive agents in a future war may pollute drinking water and water sources, creating a danger to human health. The experimental data indicate that the ''Drinking Water Decontamination and Purification Agent'' (DDPA) has a higher purification effectiveness than the ''Drinking Water Purification Powder'' (DPP) for falloutcontaminated water and /sup 131/I-contaminated water, while the ''Aqueous /sup 131/I Radioactivity Purifier'' (AIRP) has a higher purification effectiveness than DPP for /sup 131/I-contaminated water. DDPA consists of potassium permanganate, ferrous sulfate, ferric sulfate, disodium phosphate, No. 2 activated charcoal, earth, barium hydroxide, alum, and aluminium hydroxychloride. DPP consists of activated charcoal, bentonite, sodium phosphate, silver sulfate and aluminium hydroxychloride. AIRP consists of potassium permanganate, ferrous sulfate, ferric sulfate, disodium phosphate, No. 2 activated charcoal, earth, and aluminium hydroxychloride. It is concluded that the 13 common materials tested are effective in purifying radioactive water. Includes 2 tables.

  1. Determination of inhibitory concentrations of antiviral agents in cell culture by use of an enzyme immunoassay with virus-specific, peroxidase-labeled monoclonal antibodies.

    PubMed Central

    van Tiel, F H; Boere, W A; Harmsen, T; Kraaijeveld, C A; Snippe, H

    1985-01-01

    An enzyme immunoassay (EIA) to determine 50% inhibitory concentrations of drugs which suppress Semliki Forest virus replication is described. Inhibition of virus replication was measured in L-cells, seeded as monolayers in 96-well plates by use of horseradish peroxidase-labeled monoclonal antibodies directed against the E1 glycoprotein of Semliki Forest virus. The antiviral agents tested were cycloheximide, tunicamycin, NH4Cl, and disodium cromoglycate. The 50% inhibitory concentration of these antiviral agents was arbitrarily defined as the concentration of drug, in culture medium, associated with 50% reduction of the control absorbance value measured on Semliki Forest virus-infected cells without drug in the culture fluid. Twenty-two hours after infection the 50% inhibitory concentrations of the drugs were 0.2 microgram/ml for cycloheximide, 0.8 microgram/ml for tunicamycin, 0.3 mg/ml for NH4Cl, and 4.9 mg/ml for disodium cromoglycate. These values are similar to those determined by others with conventional methods of virus quantification. This test is sensitive and easy to perform and therefore is suited for large-scale experiments. PMID:3925876

  2. TLC--densitometric method for qualitative analysis of betamethasone and its related compounds in pharmacautical preparations.

    PubMed

    Dolowy, Małgorzata; Pyka, Alina

    2014-01-01

    A new simple and rapid TLC-densitometric procedure for the separation and identification of betamethasone and its related substances, betamethasone-17,21-dipropionate, betamethasone-17-valerate, betamethasone-21-valerate and also betamethasone disodium phosphate was developed. One of the chromatographic systems proposed in this study, which has been satisfactory applied in separation of four pairs of examined compounds was silica gel 60F254 (E. Merck, Art. 1.05554) and a mixture containing chloroform-methanol-acetic acid (99.5%) in volume composition 28:5:0.5. Densitometric measurements were done using densitometer TLC Scanner 3 at 246 nm. The proposed method was checked in terms of its specificity for the determination of betamethasone-17,21-dipropionate and betamethasone disodium phosphate in commercially available products containing both compounds, separately, as active ingredients. The results showed that the method is suitable for qualitative analysis of betamethasone derivatives in simple and combined pharmaceuticals in various dosage forms e.g., lotion and injection solution. It also can be applied in quality control of pharmaceutical formulations of betamethasone and its related compounds in form of salts and esters.

  3. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality. PMID:26515667

  4. Novel method for rapid copper chelation assessment confirmed low affinity of D-penicillamine for copper in comparison with trientine and 8-hydroxyquinolines.

    PubMed

    Říha, Michal; Karlíčková, Jana; Filipský, Tomáš; Macáková, Kateřina; Hrdina, Radomír; Mladěnka, Přemysl

    2013-06-01

    Copper is an essential trace element involved in many physiological processes. Since disorder of copper homeostasis is observed in various pathologies, copper chelators may represent a promising therapeutic tool. This study was aimed at: 1) formation of an in vitro methodology for screening of copper chelators, and 2) detailed analysis of the interaction of copper with clinically used D-penicillamine (D-PEN), triethylenetetramine (trientine), experimentally tested 8-hydroxyquinolines, and the disodium salt of EDTA as a standard chelator. Methodology based on bathocuproinedisulfonic acid disodium salt (BCS), usable at (patho)physiologically relevant pHs (4.5-7.5), enabled assessment of both cuprous and cupric ions chelation and comparison of the relative affinities of the tested compounds for copper. In the case of potent chelators, the stoichiometry could be estimated too. Clioquinol, chloroxine and EDTA formed very stable complexes with Cu(+)/Cu(2+) at all tested pHs, while copper complexes with trientine were stable only under neutral or slightly acidic conditions. Non-substituted 8-hydroxyquinoline was a less efficient copper chelator, but still unequivocally more potent than D-PEN. Both 8-hydroxyquinoline and D-PEN chelation potencies, similarly to that of trientine, were pH-dependent and decreased with pH. Moreover, only D-PEN was able to reduce cupric ions. Conclusively, BCS assay represents a rapid, simple and precise method for copper chelation measurement. In addition, lower binding affinity of D-PEN compared with 8-hydroxyquinolines and trientine was demonstrated.

  5. Surfactants, aromatic and isoprenoid compounds, and fatty acid biosynthesis inhibitors suppress Staphylococcus aureus production of toxic shock syndrome toxin 1.

    PubMed

    McNamara, Peter J; Syverson, Rae Ellen; Milligan-Myhre, Kathy; Frolova, Olga; Schroeder, Sarah; Kidder, Joshua; Hoang, Thanh; Proctor, Richard A

    2009-05-01

    Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1.

  6. Detection of contact hypersensitivity to corticosteroids in allergic contact dermatitis patients who do not respond to topical corticosteroids.

    PubMed

    Gönül, Müzeyyen; Gül, Ulker

    2005-08-01

    The delayed hypersensitivity development against topical corticosteroids which are used in allergic contact dermatitis (ACD) treatment is an important clinical problem. In our study, 41 ACD patients who did not show any response to topical corticosteroid treatment were patch tested with corticosteroid series and the commercial preparations of corticosteroids and their vehicles. In corticosteroid series, there were budesonide, bethametasone-17-valerate, triamcinolone acetonide, tixocortol pivalate, alclomethasone-17-21-dipropionate, clobetasole-17-propionate, dexamethasone-21-phosphate disodium and hydrocortisone-17-butyrate. We detected positive reaction to corticosteroids in 9 of our cases (22%) (5 single and 4 multiple). The sensitivity was mostly produced by tixocortol pivalate (6 patients). This was followed by triamcinolone acetonide (2 patients) budesonide (2 patients), alclomethasone dipropionate (2 patients), dexamethasone 21 phosphate disodium (2 patients) and betamethasone-17-valerate (1 patient). As a result, it should not be forgotten that the corticosteroids used to treat ACD patients may cause ACD themselves. In ACD patients who did not respond to corticosteroid treatment, routinely applying patch test with corticosteroids should be helpful in directing the treatment.

  7. Studies of levels of biogenic amines in meat samples in relation to the content of additives.

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

    The impact of meat additives on the concentration of biogenic amines and the quality of meat was studied. Fresh white and red meat samples were fortified with the following food additives: citric and lactic acids, disodium diphosphate, sodium nitrite, sodium metabisulphite, potassium sorbate, sodium chloride, ascorbic acid, α-tocopherol, propyl 3,4,5-trihydroxybenzoate (propyl gallate) and butylated hydroxyanisole. The content of spermine, spermidine, putrescine, cadaverine, histamine, tyramine, tryptamine and 2-phenylethylamine was determined by capillary isotachophoretic methods in meat samples (fresh and fortified) during four days of storage at 4°C. The results were applied to estimate the impact of the tested additives on the formation of biogenic amines in white and red meat. For all tested meats, sodium nitrite, sodium chloride and disodium diphosphate showed the best inhibition. However, cadaverine and putrescine were characterised by the biggest changes in concentration during the storage time of all the additives. Based on the presented data for the content of biogenic amines in meat samples analysed as a function of storage time and additives, we suggest that cadaverine and putrescine have a significant impact on meat quality.

  8. Orodispersible films in individualized pharmacotherapy: The development of a formulation for pharmacy preparations.

    PubMed

    Visser, J Carolina; Woerdenbag, Herman J; Crediet, Stefan; Gerrits, Edwin; Lesschen, Marjan A; Hinrichs, Wouter L J; Breitkreutz, Jörg; Frijlink, Henderik W

    2015-01-15

    Orodispersible films (ODFs) are promising drug delivery systems for customized small scale pharmacy preparations. The aim of the present study was to develop a versatile casting solution suitable for the extemporaneous production of ODFs to which active pharmaceutical ingredients (APIs) can be added. Different combinations of film forming agents and other excipients and different casting heights were tested for their suitability for production of ODFs. The best suitable casting solution contained hypromellose, carbomer, glycerol, disodium EDTA and trometamol. This casting solution was used to prepare ODFs containing water-soluble APIs (enalapril maleate and prednisolone disodium phosphate) and a poorly water-soluble API (diazepam) for which ethanol 96% was used as co-solvent.The water-soluble APIs as well as ethanol influenced the viscosity of the casting solution, mechanical properties and disintegration time of the ODFs. All ODFs containing API met the requirements on uniformity of mass and uniformity of content set by the European Pharmacopoeia (2014) (Ph. Eur.) 8th edition. In conclusion, ODFs of good pharmaceutical quality can be prepared on small scale. Hereby opening the perspective of using ODFs for individualized pharmacotherapy. PMID:25448577

  9. TLC--densitometric method for qualitative analysis of betamethasone and its related compounds in pharmacautical preparations.

    PubMed

    Dolowy, Małgorzata; Pyka, Alina

    2014-01-01

    A new simple and rapid TLC-densitometric procedure for the separation and identification of betamethasone and its related substances, betamethasone-17,21-dipropionate, betamethasone-17-valerate, betamethasone-21-valerate and also betamethasone disodium phosphate was developed. One of the chromatographic systems proposed in this study, which has been satisfactory applied in separation of four pairs of examined compounds was silica gel 60F254 (E. Merck, Art. 1.05554) and a mixture containing chloroform-methanol-acetic acid (99.5%) in volume composition 28:5:0.5. Densitometric measurements were done using densitometer TLC Scanner 3 at 246 nm. The proposed method was checked in terms of its specificity for the determination of betamethasone-17,21-dipropionate and betamethasone disodium phosphate in commercially available products containing both compounds, separately, as active ingredients. The results showed that the method is suitable for qualitative analysis of betamethasone derivatives in simple and combined pharmaceuticals in various dosage forms e.g., lotion and injection solution. It also can be applied in quality control of pharmaceutical formulations of betamethasone and its related compounds in form of salts and esters. PMID:25745764

  10. Hypermanganesemia with Dystonia, Polycythemia and Cirrhosis (HMDPC) due to mutation in the SLC30A10 gene.

    PubMed

    Mukhtiar, Khairunnisa; Ibrahim, Shahnaz; Tuschl, Karin; Mills, Phillipa

    2016-10-01

    Manganese (Mn) is an essential element for metabolic pathways but it can be toxic when present in excessive amounts in the body. Hypermanganesemia along with dystonia, polycythemia, characteristic MRI brain findings in the basal ganglia, and chronic liver disease are the hallmarks of an inherited Mn transporter defect due to mutations in the SLC30A10 gene. We are reporting three siblings who presented with features of dystonia, polycythemia, MRI brain showing basal ganglia hyperintensity on T1 weighted images and chronic liver disease. Blood Mn levels were markedly elevated in the affected patients. Mutation analysis of DNA samples of the affected children confirmed a homozygous missense mutation in SLC30A10. Chelation therapy with intravenous disodium calcium edetate was started in two siblings and led to a marked decrease in whole blood Mn. Oral Penicillamine was later added to the therapy which further improved blood Mn levels. This is a rare disorder and is one of the potentially treatable inherited metal storage disorders. It can be fatal if left untreated. Penicillamine may be an effective alternative to disodium calcium edetate.

  11. Neuropharmacological efficacy of the traditional Japanese Kampo medicine yokukansan and its active ingredients.

    PubMed

    Ikarashi, Yasushi; Mizoguchi, Kazushige

    2016-10-01

    Dementia is a progressive neurodegenerative disorder with cognitive dysfunction, and is often complicated by behavioral and psychological symptoms of dementia (BPSD) including excitement, aggression, and hallucinations. Typical and atypical antipsychotics are used for the treatment of BPSD, but induce adverse events. The traditional Japanese Kampo medicine yokukansan (YKS), which had been originated from the traditional Chinese medicine Yi-Gan-San, has been reported to improve BPSD without severe adverse effects. In the preclinical basic studies, there are over 70 research articles indicating the neuropharmacological efficacies of YKS. In this review, we first describe the neuropharmacological actions of YKS and its bioactive ingredients. Multiple potential actions for YKS were identified, which include effects on serotonergic, glutamatergic, cholinergic, dopaminergic, adrenergic, and GABAergic neurotransmissions as well as neuroprotection, anti-stress effect, promotion of neuroplasticity, and anti-inflammatory effect. Geissoschizine methyl ether (GM) in Uncaria hook and 18β-glycyrrhetinic acid (GA) in Glycyrrhiza were responsible for several pharmacological actions of YKS. Subsequently, we describe the pharmacokinetics of GM and GA in rats. These ingredients were absorbed into the blood, crossed the blood-brain barrier, and reached the brain, in rats orally administered YKS. Moreover, autoradiography showed that [(3)H]GM predominantly distributed in the frontal cortex and [(3)H]GA in the hippocampus. Thus, YKS is a versatile herbal remedy with a variety of neuropharmacological effects, and may operate as a multicomponent drug including various active ingredients. PMID:27373856

  12. Mechanism of mechanically induced intercellular calcium waves in rabbit articular chondrocytes and in HIG-82 synovial cells.

    PubMed

    Grandolfo, M; Calabrese, A; D'Andrea, P

    1998-03-01

    Intercellular communication through gap junctions allows tissue coordination of cell metabolism and sensitivity to extracellular stimuli. Intercellular Ca2+ signaling was investigated with digital fluorescence video imaging in primary cultures of articular chondrocytes and in HIG-82 synovial cells. In both cell types, mechanical stimulation of a single cell induced a wave of increased Ca2+ that was communicated to surrounding cells. Intercellular Ca2+ spreading was inhibited by 18alpha-glycyrrhetinic acid, demonstrating the involvement of gap junctions in signal propagation. In the absence of extracellular Ca2+, mechanical stimulation induced communicated Ca2+ waves similar to controls; however, the number of HIG-82 cells recruited decreased significantly. Mechanical stress induced Ca2+ influx both in the stimulated chondrocyte and HIG-82 cell, but not in the adjacent cells, as assessed by the Mn2+ quenching technique. Treatment of cells with thapsigargin and with the phospholipase C (PLC) inhibitor U73122 blocked mechanically induced signal propagation. These results provide evidence that in chondrocytes and in HIG-82 synovial cells, mechanical stimulation activates PLC, thus leading to an increase of intracellular inositol 1,4,5-trisphosphate. The second messenger, by permeating gap junctions, stimulates intracellular Ca2+ release in neighboring cells. It is concluded that intercellular Ca2+ waves may provide a mechanism to coordinate tissue responses in joint physiology.

  13. Osteoclastogenesis is influenced by modulation of gap junctional communication with antiarrhythmic peptides.

    PubMed

    Kylmäoja, Elina; Kokkonen, Hanna; Kauppinen, Kyösti; Hussar, Piret; Sato, Tetsuji; Haugan, Ketil; Larsen, Bjarne Due; Tuukkanen, Juha

    2013-03-01

    Osteoclasts are formed by the fusion of mononuclear precursor cells of the monocyte-macrophage lineage. Among several putative mechanisms, gap-junctional intercellular communication (GJC) has been proposed to have a role in osteoclast fusion and bone resorption. We examined the role of GJC in osteoclastogenesis and in vitro bone resorption with mouse bone marrow hematopoietic stem cells and RAW 264.7 cells. Blocking of gap junctions with 18-α-glycyrrhetinic acid (18GA) led to inhibition of osteoclastogenesis and in vitro bone resorption. Similarly, the GJC inhibitor GAP27 inhibited osteoclast formation. GJC modulation with the antiarrhythmic peptides (AAPs) led to increased amounts of multinuclear RAW 264.7 osteoclasts as well as increased number of nuclei per multinuclear cell. In the culture of bone marrow hematopoietic stem cells in the presence of bone marrow stromal cells AAP reduced the number of osteoclasts, and coculture of MC3T3-E1 preosteoblasts with RAW 264.7 macrophages prevented the action of AAPs to promote osteoclastogenesis. The present data indicate that AAPs modulate the fusion of the pure culture of cells of the monocyte-macrophage lineage. However, the fusion is influenced by GJC in cells of the osteoblast lineage.

  14. Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation.

    PubMed

    Andrikopoulos, Nikolaos K; Kaliora, Andriana C; Assimopoulou, Andreana N; Papapeorgiou, Vassilios P

    2003-05-01

    Naturally occurring gums and resins with beneficial pharmaceutical and nutraceutical properties were tested for their possible protective effect against copper-induced LDL oxidation in vitro. Chiosmastic gum (CMG) (Pistacia lentiscus var. Chia resin) was the most effective in protecting human LDL from oxidation. The minimum and maximum doses for the saturation phenomena of inhibition of LDL oxidation were 2.5 mg and 50 mg CMG (75.3% and 99.9%, respectively). The methanol/water extract of CMG was the most effective compared with other solvent combinations. CMG when fractionated in order to determine a structure-activity relationship showed that the total mastic essential oil, collofonium-like residue and acidic fractions of CMG exhibited a high protective activity ranging from 65.0% to 77.8%. The other natural gums and resins (CMG resin 'liquid collection', P. terebinthus var. Chia resin, dammar resin, acacia gum, tragacanth gum, storax gum) also tested as above, showed 27.0%-78.8% of the maximum LDL protection. The other naturally occurring substances, i.e. triterpenes (amyrin, oleanolic acid, ursolic acid, lupeol, 18-a-glycyrrhetinic acid) and hydroxynaphthoquinones (naphthazarin, shikonin and alkannin) showed 53.5%-78.8% and 27.0%-64.1% LDL protective activity, respectively. The combination effects (68.7%-76.2% LDL protection) of ursolic-, oleanolic- and ursodeoxycholic- acids were almost equal to the effect (75.3%) of the CMG extract in comparable doses. PMID:12748987

  15. Carbenoxolone induces oxidative stress in liver mitochondria, which is responsible for transition pore opening.

    PubMed

    Salvi, Mauro; Fiore, Cristina; Battaglia, Valentina; Palermo, Mario; Armanini, Decio; Toninello, Antonio

    2005-05-01

    Carbenoxolone (Cbx), a derivative of glycyrrhetinic acid, which has been found to affect mineralocorticoid and glucocorticoid receptors, induces swelling and membrane potential collapse when added to Ca(2+)-loaded liver mitochondria at 10 microM concentrations. These effects are strictly correlated with hydrogen peroxide generation, increase in oxygen uptake, and sulfhydryl and pyridine nucleotide oxidation. Cyclosporin A, bongkrekic acid, and N-ethylmaleimide completely abolish all the above-described effects, suggesting that Cbx can be considered an inducer of mitochondrial permeability transition by means of oxidative stress. Cbx can also trigger the apoptotic pathway because the above events are also correlated with the loss of cytochrome c. These effects are probably related to the conjugated carbonyl oxygen in C-11, which produces reactive oxygen species by interacting with the mitochondrial respiratory chain, mainly at the level of complex I but, most likely, also with complex III. The oxidative stress induced by Cbx, which is responsible for pore opening, excludes that this is related to a genomic effect of the compound. PMID:15677764

  16. Identification of the 11 beta-hydroxysteroid dehydrogenase type 1 mRNA and protein in human mononuclear leukocytes.

    PubMed

    Fiore, C; Nardi, A; Dalla Valle, L; Pellati, D; Krozowski, Z; Colombo, L; Armanini, D

    2009-10-01

    The enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) catalyzes the interconversion between inactive 11-ketoglucocorticoids and their active 11beta-hydroxy derivatives, such as cortisol and corticosterone. We have investigated the expression of 11beta-HSD1 in freshly isolated human peripheral mononuclear leukocytes (MNL). The presence of 11beta-HSD1 mRNA was demonstrated in total RNA by RT-PCR using specific primers designed on the 4th and 5th exons of the human 11beta-HSD1 gene. Fragments of the expected size were consistently detected on agarose gels, and sequencing showed complete identity with the corresponding sequence deposited in GenBank. The occurrence of 11beta-HSD1 protein was established by Western immunoblot analysis with a specific polyclonal antibody. Enzyme oxo-reductase activity was investigated by incubating 12 samples of MNL isolated from from 8 subjects with [3H]cortisone and formation of cortisol was established only in 4 subjects (yield range: 0.15-1.3%) after acetylation and TLC, blank subtraction and correction for losses. 18beta-Glycyrrhetinic acid, an inhibitor of 11 beta-HSD1, reduced cortisol production below detection limit. Dehydrogenase activity could not be demonstrated. It is suggested that, although enzyme activity of 11beta-HSD1 in circulating MNL is low, it is apparently ready for enhancement after MNL migration to sites of inflammation. PMID:19235128

  17. Mechanical signaling coordinates the embryonic heartbeat.

    PubMed

    Chiou, Kevin K; Rocks, Jason W; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F; Prosser, Benjamin L; Discher, Dennis E; Liu, Andrea J

    2016-08-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts-consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  18. The comparative pharmacokinetics of four bioactive ingredients after administration of Ramulus Cinnamomi-Radix Glycyrrhizae herb pair extract, Ramulus Cinnamomi extract and Radix Glycyrrhizae extract.

    PubMed

    Wang, Shengnan; Sun, Lijiao; Gu, Liqiang; Zhang, Yuanyuan; Zhao, Simin; Zhao, Long-Shan; Bi, Kai-Shun; Chen, Xiaohui

    2016-08-01

    Ramulus Cinnamomi (RC)-Radix Glycyrrhizae (RG) is a classic herb pair, which is commonly used as a fixed form to treat cardiovascular disease in the clinic. Our work aimed to compare the pharmacokinetic difference of cinnamic acid, liquiritin, isoliquiritigenin and glycyrrhetinic acid in rats after oral administration of the RC-RG herb pair extracts [Guizhigancao Decoction (GGD) and Lingguizhugan Decoction (LGZGD)] and the single RC or RG extract. A HPLC-MS method was developed and validated to study comparative pharmacokinetics. The pharmacokinetic parameters (Cmax , AUC, MRT) of four compounds between the RC-RG herb pair group and the single herb (RC or RG) group showed significant differences (p < 0.05). Compared with the single herb (RC or RG) group, higher peak concentration, slower elimination and larger exposure could be observed after giving the RC-RG herb-pair extracts. The pharmacokinetic differences might indicate the relativity of remedy in the RC-RG herb pair and provide scientific information for rational administration of the drug in the clinic. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26694528

  19. Neuropharmacological efficacy of the traditional Japanese Kampo medicine yokukansan and its active ingredients.

    PubMed

    Ikarashi, Yasushi; Mizoguchi, Kazushige

    2016-10-01

    Dementia is a progressive neurodegenerative disorder with cognitive dysfunction, and is often complicated by behavioral and psychological symptoms of dementia (BPSD) including excitement, aggression, and hallucinations. Typical and atypical antipsychotics are used for the treatment of BPSD, but induce adverse events. The traditional Japanese Kampo medicine yokukansan (YKS), which had been originated from the traditional Chinese medicine Yi-Gan-San, has been reported to improve BPSD without severe adverse effects. In the preclinical basic studies, there are over 70 research articles indicating the neuropharmacological efficacies of YKS. In this review, we first describe the neuropharmacological actions of YKS and its bioactive ingredients. Multiple potential actions for YKS were identified, which include effects on serotonergic, glutamatergic, cholinergic, dopaminergic, adrenergic, and GABAergic neurotransmissions as well as neuroprotection, anti-stress effect, promotion of neuroplasticity, and anti-inflammatory effect. Geissoschizine methyl ether (GM) in Uncaria hook and 18β-glycyrrhetinic acid (GA) in Glycyrrhiza were responsible for several pharmacological actions of YKS. Subsequently, we describe the pharmacokinetics of GM and GA in rats. These ingredients were absorbed into the blood, crossed the blood-brain barrier, and reached the brain, in rats orally administered YKS. Moreover, autoradiography showed that [(3)H]GM predominantly distributed in the frontal cortex and [(3)H]GA in the hippocampus. Thus, YKS is a versatile herbal remedy with a variety of neuropharmacological effects, and may operate as a multicomponent drug including various active ingredients.

  20. ATP Release from Vascular Endothelia Occurs Across Cx43 Hemichannels and Is Attenuated during Hypoxia

    PubMed Central

    Zug, Stephanie; El Kasmi, Karim C.; Eltzschig, Holger K.

    2008-01-01

    Background Extracellular ATP is an important signaling molecule for vascular adaptation to limited oxygen availability (hypoxia). Here, we pursued the contribution of vascular endothelia to extracellular ATP release under hypoxic conditions. Methodology, Principal Findings We gained first insight from studying ATP release from endothelia (HMEC-1) pre-exposed to hypoxia. Surprisingly, we found that ATP release was significantly attenuated following hypoxia exposure (2% oxygen, 22±3% after 48 h). In contrast, intracellular ATP was unchanged. Similarly, lactate-dehydrogenase release into the supernatants was similar between normoxic or hypoxic endothelia, suggesting that differences in lytic ATP release between normoxia or hypoxia are minimal. Next, we used pharmacological strategies to study potential mechanisms for endothelial-dependent ATP release (eg, verapamil, dipyridamole, 18-alpha-glycyrrhetinic acid, anandamide, connexin-mimetic peptides). These studies revealed that endothelial ATP release occurs – at least in part - through connexin 43 (Cx43) hemichannels. A real-time RT-PCR screen of endothelial connexin expression showed selective repression of Cx43 transcript and additional studies confirmed time-dependent Cx43 mRNA, total and surface protein repression during hypoxia. In addition, hypoxia resulted in Cx43-serine368 phosphorylation, which is known to switch Cx43 hemi-channels from an open to a closed state. Conclusions/Significance Taken together, these studies implicate endothelial Cx43 in hypoxia-associated repression of endothelial ATP release. PMID:18665255

  1. A Systematic Review of the Anticancer Properties of Compounds Isolated from Licorice (Gancao).

    PubMed

    Tang, Zheng-Hai; Li, Ting; Tong, Yun-Guang; Chen, Xiao-Jia; Chen, Xiu-Ping; Wang, Yi-Tao; Lu, Jin-Jian

    2015-12-01

    Licorice (Gancao in Chinese) has been used worldwide as a botanical source in medicine and as a sweetening agent in food products for thousands of years. Triterpene saponins and flavonoids are its main ingredients that exhibit a variety of biological activities, including hepatoprotective, antiulcer, anti-inflammatory, antiviral and anticancer effects among others. This review attempts to summarize the current knowledge on the anticancer properties and mechanisms of the compounds isolated from licorice and obtain new insights for further research and development of licorice. A broad spectrum of in vitro and in vivo studies have recently demonstrated that the mixed extracts and purified compounds from licorice exhibit evident anticancer properties by inhibition of proliferation, induction of cell cycle arrest, apoptosis, autophagy, differentiation, suppression of metastasis, angiogenesis, and sensitization of chemotherapy or radiotherapy. A combined treatment of licorice compounds and clinical chemotherapy drugs remarkably enhances anticancer effects and reduces the side effects of chemotherapeutics. Furthermore, glycyrrhizic acid and glycyrrhetinic acid in licorice have been indicated to present obvious liver-targeting effects in targeted drug delivery systems for hepatocellular carcinoma treatment.

  2. Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching

    PubMed Central

    Kuzma-Kuzniarska, Maria; Yapp, Clarence; Pearson-Jones, Thomas W.; Jones, Andrew K.; Hulley, Philippa A.

    2014-01-01

    Abstract. Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows quantitative measurement of gap junction function in living cells. It is based on diffusion-dependent redistribution of a gap junction-permeable fluorescent dye. Using FRAP, we showed that human tenocytes form functional gap junctions in monolayer and three-dimensional (3-D) collagen I culture. Fluorescently labeled tenocytes following photobleaching rapidly reacquired the fluorescent dye from neighboring cells, while HeLa cells, which do not communicate by gap junctions, remained bleached. Furthermore, both 18 β-glycyrrhetinic acid and carbenoxolone, standard inhibitors of gap junction activity, impaired fluorescence recovery in tendon cells. In both monolayer and 3-D cultures, intercellular communication in isolated cells was significantly decreased when compared with cells forming many cell-to-cell contacts. In this study, we used FRAP as a tool to quantify and experimentally manipulate the function of gap junctions in human tenocytes in both two-dimensional (2-D) and 3-D cultures. PMID:24390370

  3. Connexin 43 Mediates White Adipose Tissue Beiging by Facilitating the Propagation of Sympathetic Neuronal Signals.

    PubMed

    Zhu, Yi; Gao, Yong; Tao, Caroline; Shao, Mengle; Zhao, Shangang; Huang, Wei; Yao, Ting; Johnson, Joshua A; Liu, Tiemin; Cypess, Aaron M; Gupta, Olga; Holland, William L; Gupta, Rana K; Spray, David C; Tanowitz, Herbert B; Cao, Lei; Lynes, Matthew D; Tseng, Yu-Hua; Elmquist, Joel K; Williams, Kevin W; Lin, Hua V; Scherer, Philipp E

    2016-09-13

    "Beige" adipocytes reside in white adipose tissue (WAT) and dissipate energy as heat. Several studies have shown that cold temperature can activate pro-opiomelanocortin-expressing (POMC) neurons and increase sympathetic neuronal tone to regulate WAT beiging. WAT, however, is traditionally known to be sparsely innervated. Details regarding the neuronal innervation and, more importantly, the propagation of the signal within the population of "beige" adipocytes are sparse. Here, we demonstrate that beige adipocytes display an increased cell-to-cell coupling via connexin 43 (Cx43) gap junction channels. Blocking of Cx43 channels by 18α-glycyrrhetinic acid decreases POMC-activation-induced adipose tissue beiging. Adipocyte-specific deletion of Cx43 reduces WAT beiging to a level similar to that observed in denervated fat pads. In contrast, overexpression of Cx43 is sufficient to promote beiging even with mild cold stimuli. These data reveal the importance of cell-to-cell communication, effective in cold-induced WAT beiging, for the propagation of limited neuronal inputs in adipose tissue. PMID:27626200

  4. Nonsteroidal anti-inflammatory drug activated gene-1 (NAG-1) modulators from natural products as anti-cancer agents.

    PubMed

    Yang, Min Hye; Kim, Jinwoong; Khan, Ikhlas A; Walker, Larry A; Khan, Shabana I

    2014-04-01

    Natural products are rich sources of gene modulators that may be useful in prevention and treatment of cancer. Recently, nonsteroidal anti-inflammatory drug (NSAID) activated gene-1 (NAG-1) has been focused as a target of action against diverse cancers like colorectal, pancreatic, prostate, and breast. A variety of natural agents have been reported to play a pivotal role in regulation of NAG-1 through multiple transcriptional mechanisms. The aim of this paper is to review the NAG-1 modulators derived from natural products including plants, marine organisms, and microorganisms. Plant extracts belonging to the families of Fabaceae (Astragalus membranaceus), Ranunculaceae (Coptis chinensis), Menispermaceae (Coscinium fenestratum), Umbelliferae (Pleurospermum kamtschaticum), Lamiaceae (Marubium vulgare), and Rosaceae (Prunus serotina) increased the protein expression of NAG-1 in human colon cancer or hepatocarcinoma cells. Phytochemicals in the class of flavonoids (apigenin, quercetin, isoliquiritigenin, and 2'-hydroxyflavanone), isoflavonoids (formononetin and genistein), catechins (epigallocatechin gallate and epicatechin gallate), stilbenoids (resveratrol and pinosylvin), phenolics (6-gingerol), phloroglucinols (rottlerin and aspidin PB), terpenoids (18 α-glycyrrhetinic acid, platycodin D, pseudolaric acid B, and xanthorrhizol), alkaloids (berberine, capsaicin, and indole-3-carbinol), lignans (isochaihulactone), anthraquinones (damnacanthal), and allyl sulfides (diallyl disulfide) elicited NAG-1 overexpression in various cancer cells. Pectenotoxin-2 from marine organisms and prodigiosin and anisomycin from microorganisms were also reported as NAG-1 modulators. Several transcription factors including EGR-1, p53, ATF-3, Sp1 and PPARγ were involved in natural products-induced NAG-1 transcriptional signaling pathway. PMID:24530873

  5. Treatment of pruritus in mild-to-moderate atopic dermatitis with a topical non-steroidal agent.

    PubMed

    Veraldi, Stefano; De Micheli, Paolo; Schianchi, Rossana; Lunardon, Luisa

    2009-06-01

    Atopiclair (Zarzenda) is a topical non-steroidal anti-inflammatory agent for the treatment of allergic diseases of the skin. Three main ingredients are contained in this product: glycyrrhetinic acid, telmesteine and Vitis vinifera extracts. Other ingredients include: allantoin, alpha-bisabolol, capryloyl glycine, hyaluronic acid, shea butter and tocopheryl acetate. Two previous randomized, double-blind, vehicle-controlled clinical studies provided evidence that Atopiclair is effective in the treatment of atopic dermatitis. This article presents an open, multicenter, sponsor-free, study on the anti-pruritic activity of this product in adult patients with mild-to-moderate atopic dermatitis. The Median Visual Analogue Scale (VAS) values were: at the start of the study (TO), median VAS was 48.5 mm; three weeks later (T1), median VAS was 34.1 mm (-14.4 mm from baseline); six weeks later (T2), median VAS was 24.6 mm (-23.9 mm from baseline). Statistical analysis revealed that differences between TO versus T1, TO versus T2 and T1 versus T2 were highly significant (p<0.001). Side effects (local burning) were relatively common, although mild in severity. On the basis of the results of this study, Atopiclair showed efficacy in relief of pruritus in adult patients with mild-to-moderate atopic dermatitis. PMID:19537379

  6. A randomised, double-blind, vehicle-controlled study to evaluate the efficacy and safety of MAS063D (Atopiclair) in the treatment of mild to moderate atopic dermatitis.

    PubMed

    Belloni, G; Pinelli, S; Veraldi, S

    2005-01-01

    MAS063D (Atopiclair is a hydrolipidic cream that has been developed for the management of atopic dermatitis (AD). The putative active ingredients of MAS063D are hyaluronic acid, telmesteine, Vitis vinifera, glycyrrhetinic acid. A five-week study in 30 adult patients with mild to moderate AD showed that MAS063D offered significant benefits over a vehicle-only control. MAS063D improved the total body area affected (17.2% --> 13.2%, p < 0.001), itch score (2.7 --> 1.3 on a 10-point scale, p = 0.001) and EASI score (28.3 --> 24.3, p = 0.024) after 22 days treatment compared to baseline. The patients' opinion of MAS063D (patient's view of itch control, and view of study substance) was rated by participating patients as significantly better than control (p = 0.008, p = 0.042 respectively). Based on these preliminary results in a small scale study, it is suggested that MAS063D is a possible new treatment option for improving signs and symptoms in adults with mild to moderate AD. PMID:15701590

  7. Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo.

    PubMed

    Cheng, Mingrong; Gao, Xiaoyan; Wang, Yong; Chen, Houxiang; He, Bing; Li, Yingchun; Han, Jiang; Zhang, Zhiping

    2013-01-01

    Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival.

  8. A validated high performance liquid chromatograph-photodiode array method for simultaneous determination of 10 bioactive components in compound hongdoushan capsule

    PubMed Central

    Zhu, Liancai; Yang, Xian; Tan, Jun; Wang, Bochu; Zhang, Xue

    2014-01-01

    Background: The compound Hongdoushan capsule (CHC) is widely known as compound herbal preparation and is often used to treat ovarian cancer and breast cancer, and to enhance the body immunity, etc., in clinical practice. Objective: To determine simultaneously 10 bioactive components from CHC, namely glycyrrhetinic acid, liquiritin, glycyrrhizin, baccatin III, 10-deacetylbaccatin III, cephalomannine, taxol, ginsenoside Rg1, ginsenoside Re, and ginsenoside Rb1. Materials and Methods: A high performance liquid chromatograph method coupled with photodiode array detector was developed and validated for the 1st time. Chromatographic analysis was performed on a SHIMADZU C18 by utilizing a gradient elution program. The mobile phase was acetonitrile (A)-water (B) at a flow rate of 0.8 mL/min. Results: The calibration curve was linear over the investigated concentration ranges with the values of r2 higher than 0.9993 for all the 10 bioactive components. The average recovery rates range from 98.4% to 100.5% with relative standard deviations ≤2.9%. The developed method was successfully applied to analyze 10 compounds in six CHC samples from different batches. In addition, the herbal sources of 32 chromatographic peaks were identified through comparative studying on chromatograms of standard, the respective extracts of Hongdoushan, RenShen, GanCao, and CHC. Conclusion: All the results imply that the accurate and reproducible method developed has high separation rate and enables the determination of 10 bioactive components in a single run for the quality control of CHC. PMID:24696551

  9. Metabolism of bupropion by baboon hepatic and placental microsomes

    PubMed Central

    Wang, Xiaoming; Abdelrahman, Doaa R.; Fokina, Valentina M.; Hankins, Gary D.V.; Ahmed, Mahmoud S.; Nanovskaya, Tatiana N.

    2011-01-01

    The aim of this investigation was to determine the biotransformation of bupropion by baboon hepatic and placental microsomes, identify the enzyme(s) catalyzing the reaction(s) and determine its kinetics. Bupropion was metabolized by baboon hepatic and placental microsomes to hydroxybupropion (OH-BUP), threo- (TB) and erythrohydrobupropion (EB). OH-bupropion was the major metabolite formed by hepatic microsomes (Km 36 ± 6 µM, Vmax 258 ± 32 pmol mg protein−1 min−1), however the formation of OH-BUP by placental microsomes was below the limit of quantification. The apparent Km values of bupropion for the formation of TB and EB by hepatic and placental microsomes were similar. The selective inhibitors of CYP2B6 (ticlopidine and phencyclidine) and monoclonal antibodies raised against human CYP2B6 isozyme caused 80% inhibition of OH-BUP formation by baboon hepatic microsomes. The chemical inhibitors of aldo-keto reductases (flufenamic acid), carbonyl reductases (menadione), and 11β-hydroxysteroid dehydrogenases (18β-glycyrrhetinic acid) significantly decreased the formation of TB and EB by hepatic and placental microsomes. Data indicate that CYP2B of baboon hepatic microsomes is responsible for biotransformation of bupropion to OH-BUP, while hepatic and placental short chain dehydrogenases/reductases and to a lesser extent aldo-keto reductases are responsible for the reduction of bupropion to TB and EB. PMID:21570381

  10. Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching

    NASA Astrophysics Data System (ADS)

    Kuzma-Kuzniarska, Maria; Yapp, Clarence; Pearson-Jones, Thomas W.; Jones, Andrew K.; Hulley, Philippa A.

    2014-01-01

    Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows quantitative measurement of gap junction function in living cells. It is based on diffusion-dependent redistribution of a gap junction-permeable fluorescent dye. Using FRAP, we showed that human tenocytes form functional gap junctions in monolayer and three-dimensional (3-D) collagen I culture. Fluorescently labeled tenocytes following photobleaching rapidly reacquired the fluorescent dye from neighboring cells, while HeLa cells, which do not communicate by gap junctions, remained bleached. Furthermore, both 18 β-glycyrrhetinic acid and carbenoxolone, standard inhibitors of gap junction activity, impaired fluorescence recovery in tendon cells. In both monolayer and 3-D cultures, intercellular communication in isolated cells was significantly decreased when compared with cells forming many cell-to-cell contacts. In this study, we used FRAP as a tool to quantify and experimentally manipulate the function of gap junctions in human tenocytes in both two-dimensional (2-D) and 3-D cultures.

  11. Qualitative/Chemical Analyses of Ankaferd Hemostat and Its Antioxidant Content in Synthetic Gastric Fluids

    PubMed Central

    Koluman, Ahmet; Akar, Nejat; Malkan, Umit Y.; Haznedaroglu, Ibrahim C.

    2016-01-01

    Introduction. Ankaferd hemostat (ABS) is the first topical haemostatic agent involving the red blood cell-fibrinogen interactions. The antihemorrhagic efficacy of ABS has been tested in controlled clinical trials. The drug induces the formation of an encapsulated complex protein web with vital erythroid aggregation. The aim of this study is to detect the essential toxicity profile and the antioxidant molecules inside ABS. Methods. The pesticides were analyzed by GC-MS and LC-MS. The determination by ICP-MS after pressure digestion was performed for the heavy metals. HPLC was used for the detection of mycotoxins. Dioxin Response Chemically Activated Luciferase Gene Expression method was used for the dioxin evaluation. TOF-MS and spectra data were evaluated to detect the antioxidants and other molecules. Results. TOF-MS spectra revealed the presence of several antioxidant molecules (including tocotrienols, vitamin E, tryptophan, estriol, galangin, apigenin, oenin, 3,4-divanillyltetrahydrofuran, TBHQ, thymol, BHA, BHT, lycopene, glycyrrhetinic acid, and tomatine), which may have clinical implications in the pharmacobiological actions of ABS. Conclusion. The safety of ABS regarding the presence of heavy metals, pesticides, mycotoxins, GMO and dioxins, and PCBs was demonstrated. Thus the present toxicological results indicated the safety of ABS. The antioxidant content of ABS should be investigated in future studies. PMID:26925418

  12. Use of potassium chloride and flavor enhancers in low sodium Cheddar cheese.

    PubMed

    Grummer, J; Bobowski, N; Karalus, M; Vickers, Z; Schoenfuss, T

    2013-03-01

    We investigated use of potassium chloride (KCl) to maintain both the salty flavor and to replace the preservative effects of salt when reducing the sodium content in natural cheese. Because salt replacers can affect flavor because of inherent off-flavors, such as bitter and metallic, we examined the use of flavor enhancers for their ability to modulate some of these undesirable sensory effects. Stirred-curd Cheddar-style cheese was manufactured using 2 cheese-making procedures (different curd knife sizes and target salting titratable acidities), in duplicate. Curd was salted with sodium chloride (NaCl) or 60% reduced sodium blends of NaCl and KCl (2 different sources). Curd was also salted at a 60% reduced sodium rate with NaCl and KCl with added flavor enhancers. A hydrolyzed vegetable protein/yeast extract blend, a natural "potassium-blocking type" flavor, disodium inosinate, or disodium guanylate were each blended with the reduced sodium salt blend and added to curd at the salting step. The resulting blocks of cheese were aged for 5 mo and evaluated monthly for chemical, microbial, and sensory differences. At 5 mo of aging, we measured liking for the cheeses using a consumer panel. Overall, cheeses were well liked by the consumer panel, and the scores of reduced sodium cheese with 2 different KCl sources were not different from those of the full-sodium control. The addition of flavor enhancers to Cheddar curd had mixed results, with one improving the consumer flavor liking only slightly over KCl, and one (disodium inosinate) significantly reducing consumer flavor liking scores, presumably due to the amount of umami flavor it contributed. Potassium chloride replacement salts sourced from different manufacturers affected the chemical and flavor properties of cheese, and changes to pH and temperature targets may be necessary to yield cheese with the moisture and pH targets desired. The cheese-making procedure used also influenced flavors observed, which resulted in

  13. Use of potassium chloride and flavor enhancers in low sodium Cheddar cheese.

    PubMed

    Grummer, J; Bobowski, N; Karalus, M; Vickers, Z; Schoenfuss, T

    2013-03-01

    We investigated use of potassium chloride (KCl) to maintain both the salty flavor and to replace the preservative effects of salt when reducing the sodium content in natural cheese. Because salt replacers can affect flavor because of inherent off-flavors, such as bitter and metallic, we examined the use of flavor enhancers for their ability to modulate some of these undesirable sensory effects. Stirred-curd Cheddar-style cheese was manufactured using 2 cheese-making procedures (different curd knife sizes and target salting titratable acidities), in duplicate. Curd was salted with sodium chloride (NaCl) or 60% reduced sodium blends of NaCl and KCl (2 different sources). Curd was also salted at a 60% reduced sodium rate with NaCl and KCl with added flavor enhancers. A hydrolyzed vegetable protein/yeast extract blend, a natural "potassium-blocking type" flavor, disodium inosinate, or disodium guanylate were each blended with the reduced sodium salt blend and added to curd at the salting step. The resulting blocks of cheese were aged for 5 mo and evaluated monthly for chemical, microbial, and sensory differences. At 5 mo of aging, we measured liking for the cheeses using a consumer panel. Overall, cheeses were well liked by the consumer panel, and the scores of reduced sodium cheese with 2 different KCl sources were not different from those of the full-sodium control. The addition of flavor enhancers to Cheddar curd had mixed results, with one improving the consumer flavor liking only slightly over KCl, and one (disodium inosinate) significantly reducing consumer flavor liking scores, presumably due to the amount of umami flavor it contributed. Potassium chloride replacement salts sourced from different manufacturers affected the chemical and flavor properties of cheese, and changes to pH and temperature targets may be necessary to yield cheese with the moisture and pH targets desired. The cheese-making procedure used also influenced flavors observed, which resulted in

  14. Facile One-Step Strategy for Highly Boosted Microbial Extracellular Electron Transfer of the Genus Shewanella.

    PubMed

    Wang, Yuan; Lv, Meiling; Meng, Qingan; Ding, Chunmei; Jiang, Lei; Liu, Huan

    2016-06-28

    High performance of bacterial extracellular electron transfer (EET) is essentially important for its practical applications in versatile bioelectric fields. We developed a facile one-step approach to dramatically boost the bacterial EET activity 75-fold by exogenous addition of ethylenediamine tetraacetic acid disodium salt (EDTA-2Na, 1 mM) into the electrochemical cells, where the anodic process of microbial EET was monitored. We propose that EDTA-2Na enables both the alternation of the local environment around the c-type cytochromes located on the outer membrane channels (OMCs), which therefore changes the redox behavior of OMCs in mediating the EET process, and the formation of densely packed biofilm that can further facilitate the EET process. As a synergistic effect, the highly boosted bacterial EET activity was achieved. The method shows good generality for versatile bioelectrical bacteria. We envision that the method is also applicable for constructing various bioelectric devices. PMID:27196945

  15. Interaction between lyotropic chromonic liquid crystals and polymers

    NASA Astrophysics Data System (ADS)

    Yao, Xuxia; Park, Jung; Srinivasarao, Mohan

    2010-03-01

    Lyotropic chromonic liquid crystals (LCLCs) consist of various dyes, drugs, etc., so their importance is self-evident. The interaction of chromonic molecules and polymers is involved in their real applications, such as the dyeing process of fibers, textiles and food, and the functionalization of drugs in vivo. In our research, polymer dispersed LCLC droplets and polymer coated LCLC cells have been fabricated. Effect of interaction was observed by optical texture of LCLCs, as the different polymers induce different director configuration of LCLCs. A textile dye-Benzopurpurine 4B, food dye-Sunset Yellow FCF, and drug-Disodium Cromoglycate mixed with water soluble polymers, proteins and textile polymers have been all studied and compared.

  16. Fast motif-network scheme for extensive exploration of complex crystal structures in silicate cathodes

    NASA Astrophysics Data System (ADS)

    Ho, Kai-Ming; Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai-Zhuang; Lin, Zijing; Zhu, Zi-Zhong

    2015-03-01

    A motif-network search scheme is proposed to study the crystal structures of the dilithium/disodium transition metal orthosilicates A2MSiO4. Using this fast and efficient method, the structures of all six combinations with A = Li or Na and M = Mn, Fe or Co were extensively explored in this work. In addition to finding all previously reported experimental structures, we discover many other different crystal structures which are highly degenerate in energy. These tetrahedral-network-based structures can be classified into 1D, 2D and 3D types. A clear trend of the structural preference in different systems is revealed and possible indicators that affect the structure stabilities are introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.

  17. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    NASA Astrophysics Data System (ADS)

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai-Zhuang; Lin, Zijing; Zhu, Zi-Zhong; Ho, Kai-Ming

    2015-10-01

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. These structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.

  18. Chiroptical spectroscopy of natural products: avoiding the aggregation effects of chiral carboxylic acids.

    PubMed

    Polavarapu, Prasad L; Donahue, Emily A; Hammer, Karissa C; Raghavan, Vijay; Shanmugam, Ganesh; Ibnusaud, Ibrahim; Nair, Divya S; Gopinath, Chithra; Habel, Deenamma

    2012-08-24

    Determination of the absolute configurations and predominant conformations of chiral natural products, occurring as carboxylic acids, using chiroptical spectroscopic methods becomes challenging due to the formation of solute aggregates (in the form of dimers, etc.) and/or solute-solvent complexes resulting from intermolecular hydrogen bonding with solvent. A hypothesis that such aggregation effects can be avoided by using corresponding sodium salts or acid anhydrides for chiroptical spectroscopic measurements has been tested. For this purpose, vibrational circular dichroism, electronic circular dichroism, and optical rotatory dispersion spectra for disodium salts of two natural products, hibiscus acid and garcinia acid, and the anhydride of acetylated garcinia acid have been measured. These experimental spectra are analyzed in combination with quantum chemical calculations of corresponding spectra. The spectral analysis for sodium salts and anhydride turned out to be simpler, suggesting that the conversion of carboxylic acids to corresponding salts or anhydride can be advantageous for the application of chiroptical spectroscopy. PMID:22877358

  19. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    NASA Astrophysics Data System (ADS)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  20. Chrysanthemum-like bismuth sulfide microcrystals: Synthesis, characterization, and properties

    NASA Astrophysics Data System (ADS)

    Jiang, Jinghui; Gao, Guanhua; Yu, Runnan; Qiu, Guanzhou; Liu, Xiaohe

    2011-02-01

    Uniform chrysanthemum-like bismuth sulfide (Bi 2S 3) microcrystals assembled from nanosheet building blocks were successfully synthesized via a convenient hydrothermal synthetic route under mild conditions in which hydrated bismuth nitrate and L-cysteine were employed to supply Bi and S source and ethylenediaminetetraacetic acid disodium salt (EDTA-Na 2) was employed as chelating agent. The influences of reaction temperatures and time on the morphologies of final products were investigated. The phase structures, morphologies, and properties of as-prepared products were investigated by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscope, and photoluminescence spectra. The possible growth mechanism for the formation of chrysanthemum-like Bi 2S 3 microcrystals was discussed on the basis of the experimental results.

  1. Asthma induced by enkephalin.

    PubMed Central

    Leslie, R D; Bellamy, D; Pyke, D A

    1980-01-01

    A total of 291 diabetics were studied to see whether an asthmatic reaction was associated with facial flushing induced by chlorpropamide and alcohol. Of these patients, 191 reported facial flushing, of whom 12 reported breathlessness as well. Of these 12, five also described wheezing, and respiratory function tests showed them to have asthma. Three of these five patients underwent further tests, which showed that the asthmatic reaction could be prevented by giving disodium cromoglycate and the specific opiate antagonist naloxone. One patient developed wheezing when given an enkephalin analogue with opiate-like activity. Asthma induced by chlorpropamide and alcohol was concluded to be mediated by endogenous peptides with opiate-like activity such as enkephalin. PMID:7357255

  2. Discrimination of Umami Tastants Using Floating Electrode-Based Bioelectronic Tongue Mimicking Insect Taste Systems.

    PubMed

    Lee, Minju; Jung, Je Won; Kim, Daesan; Ahn, Young-Joon; Hong, Seunghun; Kwon, Hyung Wook

    2015-12-22

    We report a floating electrode-based bioelectronic tongue mimicking insect taste systems for the detection and discrimination of umami substances. Here, carbon nanotube field-effect transistors with floating electrodes were hybridized with nanovesicles containing honeybee umami taste receptor, gustatory receptor 10 of Apis mellifera (AmGr10). This strategy enables us to discriminate between l-monosodium glutamate (MSG), best-known umami tastant, and non-umami substances with a high sensitivity and selectivity. It could also be utilized for the detection of MSG in liquid food such as chicken stock. Moreover, we demonstrated the synergism between MSG and disodium 5'-inosinate (IMP) for the umami taste using this platform. This floating electrode-based bioelectronic tongue mimicking insect taste systems can be a powerful platform for various applications such as food screening, and it also can provide valuable insights on insect taste systems.

  3. Effects of Pamidronate on Dental Enamel Formation Assessed by Light Microscopy, Energy-Dispersive X-Ray Analysis, Scanning Electron Microscopy, and Microhardness Testing.

    PubMed

    Soares, Ana P; do Espírito Santo, Renan F; Line, Sérgio R P; Pinto, Maria das G F; Santos, Pablo de M; Toralles, Maria Betania P; do Espírito Santo, Alexandre R

    2016-06-01

    The aim of the present work was to investigate birefringence and morphology of the secretory-stage enamel organic extracellular matrix (EOECM), and structural and mechanical properties of mature enamel of upper incisors from adult rats that had been treated with pamidronate disodium (0.5 mg/kg/week for 56 days), using transmitted polarizing and bright-field light microscopies (TPLM and BFLM), energy-dispersive X-ray (EDX) analysis, scanning electron microscopy (SEM) and microhardness testing. BFLM showed no morphological changes of the EOECM in pamidronate and control groups, but TPLM revealed a statistically significant reduction in optical retardation values of birefringence brightness of pamidronate-treated rats when compared with control animals (p0.05). The present study indicates that pamidronate can affect birefringence of the secretory-stage EOECM, which does not seem to be associated with significant changes in morphological and/or mechanical properties of mature enamel. PMID:27212049

  4. Effects of Pamidronate on Dental Enamel Formation Assessed by Light Microscopy, Energy-Dispersive X-Ray Analysis, Scanning Electron Microscopy, and Microhardness Testing.

    PubMed

    Soares, Ana P; do Espírito Santo, Renan F; Line, Sérgio R P; Pinto, Maria das G F; Santos, Pablo de M; Toralles, Maria Betania P; do Espírito Santo, Alexandre R

    2016-06-01

    The aim of the present work was to investigate birefringence and morphology of the secretory-stage enamel organic extracellular matrix (EOECM), and structural and mechanical properties of mature enamel of upper incisors from adult rats that had been treated with pamidronate disodium (0.5 mg/kg/week for 56 days), using transmitted polarizing and bright-field light microscopies (TPLM and BFLM), energy-dispersive X-ray (EDX) analysis, scanning electron microscopy (SEM) and microhardness testing. BFLM showed no morphological changes of the EOECM in pamidronate and control groups, but TPLM revealed a statistically significant reduction in optical retardation values of birefringence brightness of pamidronate-treated rats when compared with control animals (p0.05). The present study indicates that pamidronate can affect birefringence of the secretory-stage EOECM, which does not seem to be associated with significant changes in morphological and/or mechanical properties of mature enamel.

  5. Heavy Metals, Cardiovascular Disease, and the Unexpected Benefits of Chelation Therapy.

    PubMed

    Lamas, Gervasio A; Navas-Acien, Ana; Mark, Daniel B; Lee, Kerry L

    2016-05-24

    This review summarizes evidence from 2 lines of research previously thought to be unrelated: the unexpectedly positive results of TACT (Trial to Assess Chelation Therapy), and a body of epidemiological data showing that accumulation of biologically active metals, such as lead and cadmium, is an important risk factor for cardiovascular disease. Considering these 2 areas of work together may lead to the identification of new, modifiable risk factors for atherosclerotic cardiovascular disease. We examine the history of chelation up through the report of TACT. We then describe work connecting higher metal levels in the body with the future risk of cardiovascular disease. We conclude by presenting a brief overview of a newly planned National Institutes of Health trial, TACT2, in which we will attempt to replicate the findings of TACT and to establish that removal of toxic metal stores from the body is a plausible mechanistic explanation for the benefits of edetate disodium treatment.

  6. DSC study of technical grade phase change heat storage materials for solar heating applications

    SciTech Connect

    Gibbs, B.M.; Hasnain, S.M.

    1995-11-01

    Differential scanning calorimetry (DSC) was used to investigate the behavior of storage materials that undergo solid-liquid phase transitions. Heating scans were used to measure the enthalpy that can be stored and cooling scans were used to estimate the magnitude of the enthalpy that may be recovered from the storage material. The automatic and rapid thermal cycling features of the DSC system were used to study thermal decomposition that may arise from the daily duty cycle of the storage medium. In this study, DSC methods were applied to technical grade paraffin wax, calcium chloride hexahydrate and disodium hydrogen phosphate dodecahydrate. In the case of inorganic salt hydrates, DSC measurements showed a decrease in heat of fusion; thermal cycling and thermograms revealed considerable super cooling. This would lead to a reduction in storage capacity. On the other hand paraffin wax did not supercool nor were there any indications that thermal cycling or contact with metal could degrade its thermal performance.

  7. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia

    PubMed Central

    Tuschl, Karin; Meyer, Esther; Valdivia, Leonardo E.; Zhao, Ningning; Dadswell, Chris; Abdul-Sada, Alaa; Hung, Christina Y.; Simpson, Michael A.; Chong, W. K.; Jacques, Thomas S.; Woltjer, Randy L.; Eaton, Simon; Gregory, Allison; Sanford, Lynn; Kara, Eleanna; Houlden, Henry; Cuno, Stephan M.; Prokisch, Holger; Valletta, Lorella; Tiranti, Valeria; Younis, Rasha; Maher, Eamonn R.; Spencer, John; Straatman-Iwanowska, Ania; Gissen, Paul; Selim, Laila A. M.; Pintos-Morell, Guillem; Coroleu-Lletget, Wifredo; Mohammad, Shekeeb S.; Yoganathan, Sangeetha; Dale, Russell C.; Thomas, Maya; Rihel, Jason; Bodamer, Olaf A.; Enns, Caroline A.; Hayflick, Susan J.; Clayton, Peter T.; Mills, Philippa B.; Kurian, Manju A.; Wilson, Stephen W.

    2016-01-01

    Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism–dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates. PMID:27231142

  8. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

    PubMed

    Tuschl, Karin; Meyer, Esther; Valdivia, Leonardo E; Zhao, Ningning; Dadswell, Chris; Abdul-Sada, Alaa; Hung, Christina Y; Simpson, Michael A; Chong, W K; Jacques, Thomas S; Woltjer, Randy L; Eaton, Simon; Gregory, Allison; Sanford, Lynn; Kara, Eleanna; Houlden, Henry; Cuno, Stephan M; Prokisch, Holger; Valletta, Lorella; Tiranti, Valeria; Younis, Rasha; Maher, Eamonn R; Spencer, John; Straatman-Iwanowska, Ania; Gissen, Paul; Selim, Laila A M; Pintos-Morell, Guillem; Coroleu-Lletget, Wifredo; Mohammad, Shekeeb S; Yoganathan, Sangeetha; Dale, Russell C; Thomas, Maya; Rihel, Jason; Bodamer, Olaf A; Enns, Caroline A; Hayflick, Susan J; Clayton, Peter T; Mills, Philippa B; Kurian, Manju A; Wilson, Stephen W

    2016-01-01

    Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates. PMID:27231142

  9. Trinuclear Nickel Complexes with Metal-Arene Interactions Supported by Tris- and Bis(phosphinoaryl)benzene Frameworks

    PubMed Central

    Suseno, Sandy; Horak, Kyle T.; Day, Michael W.; Agapie, Theodor

    2014-01-01

    Triphosphine and diphosphine ligands with backbones designed to facilitate metal-arene interactions were employed to support multinuclear Ni complexes. Di- and trinuclear metal complexes supported by a triphosphine containing a triarylbenzene linker display diverse metal-arene binding modes. Multinuclear Ni halide complexes were isolated with strongly interacting metal centers bound to opposite faces of the coordinated arene. Upon reaction of the trinickel diiodide complex, 2, with disodium tetracarbonylferrate, a cofacial triangulo nickel(0) complex, 4, was isolated. The Ni03 cluster motif can also be supported by a para-terphenyldiphosphine, where a terminal carbon monoxide ligand replaces the third phosphine donor. All multinuclear complexes feature strong metal-arene interactions, demonstrating the use of an arene as a versatile ligand design element for small clusters. PMID:24532865

  10. Field method for sulfide determination

    SciTech Connect

    Wilson, B L; Schwarser, R R; Chukwuenye, C O

    1982-01-01

    A simple and rapid method was developed for determining the total sulfide concentration in water in the field. Direct measurements were made using a silver/sulfide ion selective electrode in conjunction with a double junction reference electrode connected to an Orion Model 407A/F Specific Ion Meter. The method also made use of a sulfide anti-oxidant buffer (SAOB II) which consists of ascorbic acid, sodium hydroxide, and disodium EDTA. Preweighed sodium sulfide crystals were sealed in air tight plastic volumetric flasks which were used in standardization process in the field. Field standards were prepared by adding SAOB II to the flask containing the sulfide crystals and diluting it to the mark with deionized deaerated water. Serial dilutions of the standards were used to prepare standards of lower concentrations. Concentrations as low as 6 ppB were obtained on lake samples with a reproducibility better than +- 10%.

  11. Bonding Analysis of Amino Resin Wood Adhesive with Pesticide Using Response Surface Method

    NASA Astrophysics Data System (ADS)

    Bono, Awang; Rajin, Mariani; Siambun, Nancy Julius

    Wood base industries are among the dominant players in Malaysia economic activities. In this research, by using Response Surface Method (RSM), studies of bonding between Disodium Tetraborate Decahydrate (DTD) pesticide and various formulation of wood adhesive i.e., Melamine-Urea-Formaldehyde (MUF) resin is carried out. The RSM formulated twenty-five MUF formulations, consisting combination of different amount of formaldehyde, melamine, urea added in stage-1 and stage-2 of resin synthesis and DTD pesticide. The liquid products of resin are then hardened and tested using Fourier Transformation Infra-Red (FTIR) and visible spectrophotometer (VIS), to analyse the bonding of the resin and pesticide. The data from the FTIR and VIS analysis were then compiled and analysed using Response Surface Method. The results show that, different amount of the formaldehyde, melamine, urea and DTD pesticide, gives specific impact to the strength of MUF resin-pesticide bonding.

  12. Novel method for the preparation of core-shell nanoparticles with movable Ag core and polystyrene loop shell

    SciTech Connect

    Liu Weijun; Zhang Zhicheng . E-mail: lwj3600@ustc.edu; He Weidong; Zheng Cheng; Ge Xuewu; Li, Jian; Liu Huarong; Jiang Hao

    2006-04-15

    Core/shell nanoparticles with movable silver (Ag) core and polystyrene (PSt) shell (Ag at PSt nanoparticle) were successfully synthesized at room temperature and under ambient pressure via two steps: {gamma}-irradiation and interfacial-initiated polymerization. Firstly, mono-dispersed Ag nanoparticles with diameters 20 nm were synthesized in inversed microemulsion by reducing silver nitrate under {gamma}-irradiation. Then, Ag nanoparticles were coated with PSt via interfacial-initiated polymerization with cumene hydroperoxide/ferrous sulfate/disodium ethylenediaminetetraacetate/sodium formaldehyde sulfoxylate (CHPO-Fe {sup 2+}-EDTA-SFS) as the redox initiation pair. The resulted Ag at PSt nanoparticles were identified by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS)

  13. Relationship between plasma calcium and QT interval of electrocardiogram in dairy cows.

    PubMed

    Daniel, R C; Moodie, E W

    1979-06-01

    Relationships between calcium of blood plasma and measurements of the electrocardiogram QT interval corrected for heart rate and interval from Q to the apex of T corrected for heart rate were investigated in six dairy cows. Calcium was varied by infusing 4.7% solution of ethylenediaminetetra-acetic acid disodium salt to induce hypocalcemia, followed by treatment with calcium borogluconate. The within-cow regressions of the intervals on calcium in plasma were significant in all four electrocardiogram leads (leads I, aVF, SIII, and SaVF). These regressions differed between cows in these same leads. Correlation coefficients between calcium and the intervals were consistently larger than --.94 in lead SIII in all cows. When the results from four of the cows similar in age and breed were analyzed separately, regression coefficients between individual cows were not significantly different. However, intervals adjusted for calcium in plasma differed between cows.

  14. Design of a Flow-Through Voltammetric Sensor Based on an Antimony-Modified Silver Electrode for Determining Lithol Rubine B in Cosmetics

    PubMed Central

    Lai-Hao, Wang; Shu-Juan, Huang

    2011-01-01

    Lithol Rubine B (LRB; the disodium salt of 3-hydroxy-4-[(4-methyl-2-sulfophenyl) azo]-2-naphthalenecarboxylic acid) was detected using high-performance liquid chromatography with an electrochemical (antimony film on silver) detector (HPLC-ECD). For direct current (DC) mode, with the current at a constant potential, and measurements with suitable experimental parameters, a linear concentration from 0.125 to 1.80 μg/mL was found. The detection limit of our method was approximately 2.0 ng/mL. An antimony-modified silver detector was used to demonstrate that LRB is electrochemically reduced in acidic media and to analyze commercial cosmetics to determine their LRB content. Findings using HPLC-ECD and HPLC with an ultraviolet detector were comparable. PMID:21603230

  15. Effect of tartarate and citrate based food additives on the micellar properties of sodium dodecylsulfate for prospective use as food emulsifier.

    PubMed

    Banipal, Tarlok S; Kaur, Harjinder; Kaur, Amanpreet; Banipal, Parampaul K

    2016-01-01

    Citrate and tartarate based food preservatives can be used to enhance the emulsifying properties of sodium dodecylsulfate (SDS) based micellar system and thus making it appropriate for food applications. Exploration of interactions between the two species is the key constraint for execution of such ideas. In this work various micellar and thermodynamic parameters of SDS like critical micellar concentration (CMC), standard Gibbs free energy of micellization (ΔG(0)mic.) etc. have been calculated in different concentrations of disodium tartarate (DST) and trisodium citrate (TSC) in the temperature range (288.15-318.15)K from the conductivity and surface tension measurements. The parameters obtained from these studies reveal the competitive nature of both the additives with SDS for available positions at the air/water interface. TSC is found to be more effective additive in order to make SDS micellar system better for its potential applications as food emulsifier. PMID:26213016

  16. Influence of sodium cations of N3 dye on the photovoltaic performance and stability of dye-sensitized solar cells.

    PubMed

    Andrade, Luísa; Zakeeruddin, Shaik M; Nazeeruddin, Mohammad K; Ribeiro, Helena Aguilar; Mendes, Adélio; Grätzel, Michael

    2009-05-11

    We report on the effect of substituting the two tetrabutyl ammonium counter ions of the standard N719 dye by sodium ions on the performance and stability of dye-sensitized solar cells (DSCs). The disodium analogue of N719 in conjunction with a non-volatile electrolyte gives a conversion efficiency of 7.6% under standard global AM 1.5 sunlight. Devices maintain 99% of their initial performance after 1000 h under full sunlight aging at 50 degrees C. Electrochemical impedance spectroscopy and photovoltage transient decay studies reveal the evolution of the solar cell parameters during aging. Remarkably, upon aging a decrease in the rate of electron back reaction with the triiodide ions across the TiO(2)/electrolyte interface appears as well as enhanced electronic conduction in the TiO(2) film.

  17. Safety Assessment of Alkyl PEG Sulfosuccinates as Used in Cosmetics.

    PubMed

    Johnson, Wilbur; Heldreth, Bart; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel C; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2015-09-01

    The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of alkyl polyethylene glycol (PEG) sulfosuccinates, which function in cosmetics mostly as surfactants/cleansing agents. Although these ingredients may cause ocular and skin irritation, dermal penetration is unlikely because of the substantial polarity and molecular size of these ingredients. The Panel considered the negative oral carcinogenicity and reproductive and developmental toxicity data on chemically related laureths (PEG lauryl ethers) and negative repeated dose toxicity and skin sensitization data on disodium laureth sulfosuccinate supported the safety of these alkyl PEG sulfosuccinates in cosmetic products, but. The CIR Expert Panel concluded that the alkyl PEG sulfosuccinates are safe in the present practices of use and concentration when formulated to be nonirritating.

  18. Full scale field demonstration on the use of hydrogen peroxide for in situ bioremediation of an aviation gasoline-contaminated aquifer (Chapter 16). Book chapter

    SciTech Connect

    Wilson, J.T.; Armstrong, J.M.; Rafai, H.S.

    1994-01-01

    The U.S. Environmental Protection Agency (EPA) and the U.S. Coast Guard conducted a joint full-scale evaluation of in situ biological treatement of Petroleum Hydrocarbons (PHCs) following spillage of aviation gasoline at a Coast Guard Air Station in Traverse City, MI. At the Coast Guard site, soil core samples were collected and analyzed to quantify aviation gasoline contamination in the aquifer. Hydraulic modeling was used to design an infiltration system that flooded all of the fuel-contaminated subsurface soil. The spill area was pretreated with groundwater, which was amended with 380 mg/L ammonium chloride, 190 mg/L disodium phosphate, and 190 mg/L potassium phosphate. The groundwater concentration of benzene in the most contaminated depth interval at the site was reduced to <1 microgram/L. Remaining alkylbenzenes were also reduced to below federal drinking water standards. (Copyright (c) 1994 by Lewis Publishers).

  19. Effect of additives on the purification of urease

    NASA Astrophysics Data System (ADS)

    Yu, X.; Wang, J.; Ulrich, J.

    2015-12-01

    The effect of additives on the purification of proteins was investigated. The target protein studied here is the enzyme urease. Studies on the purification of urease from jack bean meal were carried out. 32% (v/v) acetone was utilized to extract urease from the jack bean meal. Further purification by crystallization with the addition of 2-mercaptoethanol and EDTA disodium salt dehydrate was carried out. It was found out that the presence of additives can affect the selectivity of the crystallization. Increases in both purity and yield of the urease after crystallization were observed in the presence of additives, which were proven using both SDS-PAGE and activity. Urease crystals with a yield of 69.9% and a purity of 85.1% were obtained in one crystallization step in the presence of additives. Furthermore, the effect of additives on the thermodynamics and kinetics of urease crystallization was studied.

  20. Efficient white light generation from 2,3-diphenyl-1,2-dihydro-quinoxaline complex

    NASA Astrophysics Data System (ADS)

    Dwivedi, Y.; Kant, S.; Rai, R. N.; Rai, S. B.

    2010-11-01

    In this article, we report two organic materials dispersed in transparent poly (methyl methacrylate) matrix for efficient white light simulation under different optical excitations. A newly synthesized complex of benzoin and o-phenyldiamine is observed to be white on illumination with a blue LED. A new concept of white light emitting tube is also demonstrated. A mixture of 2,2″-([1,1'-biphenyl]-4,4'-diyldi-2,1-ethenediyl)-bis-benzenesulfonic acid disodium salt and complex is optimized to emit white light extended in the violet region on 355 nm laser excitation. The optical quality of the emitted white light is adjudged by the CIE coordinate, correlated color temperature and color rendition index in both the cases.

  1. Real-Time Dynamics of Galvanic Replacement Reactions of Silver Nanocubes and Au Studied by Liquid-Cell Transmission Electron Microscopy.

    PubMed

    Tan, Shu Fen; Lin, Guanhua; Bosman, Michel; Mirsaidov, Utkur; Nijhuis, Christian A

    2016-08-23

    We study the galvanic replacement reaction of silver nanocubes in dilute, aqueous ethylenediaminetetraacetic acid disodium salt (EDTA)-capped gold aurate solutions using in situ liquid-cell electron microscopy. Au/Ag etched nanostructures with concave faces are formed via (1) etching that starts from the faces of the nanocubes, followed by (2) the deposition of an Au layer as a result of galvanic replacement, and (3) Au deposition via particle coalescence and monomer attachment where small nanoparticles are formed during the reaction as a result of radiolysis. Analysis of the Ag removal rate and Au deposition rate provides a quantitative picture of the growth process and shows that the morphology and composition of the final product are dependent on the stoichiometric ratio between Au and Ag.

  2. AFRRI (Armed Forces Radiobiology Research Institute) reports, April-June 1986. Technical report

    SciTech Connect

    Not Available

    1986-01-01

    Contents include the following: disodium cryomoglycate, a mast-cell stabilizer, alters postradiation regional cerebral blood flow in primates; intracellular recordings from pineal cells in tissue culture: membrane properties and response to norepinephrine; gamma radiation affects active electrolyte transport by rabbit ileum: basal Na and Cl transport; histamine H2 receptors mediate morphine-induced locomotor hyperactivity of the C57BL/6J mouse; Interleukin 1 is a radioprotector; histamine decreased calcium-mediated potassium current in guinea pig hippocampal ca1 pyramidal cells; cytochemical study of developing neurotransmitter properties of dissociated sympathetic neurons grown in co-culture with dissociated pineal cells: angiotensin II-induced taste aversion learning in cats and rats and the role of the area postrema; effects of area postrema lesions on taste aversions produced by treatment with WU-2721 in the rat; and DOD nuclear mishaps.

  3. Studies on the reverse osmosis treatment of uranyl nitrate solution

    SciTech Connect

    Prabhakar, S.; Panicker, S.T.; Misra, B.M.; Ramani, P.S. )

    1992-03-01

    The aqueous effluent generated in uranium processing, particularly in the nuclear fuel fabrication step, contains mainly uranium nitrate. This requires treatment before discharge into the environment to meet stringent standards. This paper presents the performance of cellulose acetate membranes with regard to rejection of uranium under reverse osmotic conditions for feed concentrations up to 200 mg/l of uranium, which corresponds to the levels normally prevalent in the effluents. The use of additives like the disodium salt of ethylenediaminetetraacetic acid and sodium sulfate for the improvement of reverse osmosis performance of the above membranes was also investigated. In the light of the experimental results, the suitability of reverse osmosis for the decontamination of uranium effluents is discussed.

  4. Effects of supplemental protein on acid-base status and calcium metabolism of nonlactating Jersey cows.

    PubMed

    Wang, C; Beede, D K

    1990-11-01

    The objective was to study effects of 11, 15, and 19% dietary CP on acid-base status, Ca balance, and metabolic responses to intravenous infusion of disodium EDTA. Dietary protein content was increased by supplementation of hydrolyzed feather meal and distillers dried grains with solubles to a concentrate combined with cottonseed hulls (40:60). Six nonlactating, nonpregnant multiparous Jersey cows (average 6.7 yr old) were used in two balanced 3 x 3 Latin squares with 24-d periods. Increasing supplemental CP decreased blood base excess, urinary titratable base, and net base excretion, but increased urinary ammonium excretion. Calcium excretion and balance were not affected by supplemental CP. Analysis to detect heterogeneity of regression showed that response of plasma EDTA-free Ca to EDTA infusion over time was not different among treatments. Increasing supplemental protein induced mild acidosis but did not affect Ca balance or responses to Ca removal from blood (via EDTA infusion) of non-lactating cows.

  5. New platinum compounds containing the diphosphine ligand 2-(ferrocenylidene)-4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (fbpcd): Synthesis, redox behavior, and X-ray diffraction structures Of PtCl2(fbpcd) and Pt(mnt)(fbpcd)

    SciTech Connect

    Poola, Bhaskar; Hunt, Sean W; Wang, Xiaoping; Richmond, Michael G.

    2008-01-01

    The reaction of the redox-active diphosphine ligand 2-(ferrocenylidene)-4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (fbpcd) with PtCl2(1,5-cod) furnishes the platinum(II) compound PtCl2(fbpcd) (2). Treatment of 2 with disodium maleonitriledithiolate (Na(2)mnt) yields the chelating thiolate compound Pt(mnt)(fbpcd) (3). Both 2 and 3 have been fully characterized in solution by IR, UV-Vis, and NMR spectroscopies, and their molecular structures established by X-ray crystallography. The redox properties of the fbpcd ligand and compounds 2 and 3 have been investigated by cyclic voltammetry, and the composition of the HOMO and LUMO levels in these systems have been determined by extended Huckel MO calculations, the results of which are discussed with respect to electrochemical data.

  6. Optical principle of pH measurement for detection of auxin flow through cellular membrane

    NASA Astrophysics Data System (ADS)

    Podrazky, Ondrej; Mrazek, Jan; Seidl, Miroslav; Kasik, Ivan; Tobiska, Petr; Matejec, Vlastimil; Martan, Tomas; Aubrecht, Jan

    2007-05-01

    The paper shows an approach to the determination of pH changes of solutions with a fine spatial resolution by means of fiber-optic tapers and fluorescence detection. This approach can be adopted for the determination of auxin flow through celluar membranes. Spectral absorption and fluorescence of pH transducers, namely of fluorescein, carboxyfluorescein, 6,8-dihydroxy-1,3-pyrenedisulfonic acid disodium salt and 2',7'-bis(2-carbonylethyl)-5(6)-carboxyfluorescein, were tested. The approach, based on the determination of a shift of the maxima of their fluorescence peaks, was employed for processing the measured fluorescence data in bulk solutions. Suitable tapered fiber probes were prepared and in vitro demonstrated for pH monitoring in a pH range from 6 to 7.

  7. Effect of tartarate and citrate based food additives on the micellar properties of sodium dodecylsulfate for prospective use as food emulsifier.

    PubMed

    Banipal, Tarlok S; Kaur, Harjinder; Kaur, Amanpreet; Banipal, Parampaul K

    2016-01-01

    Citrate and tartarate based food preservatives can be used to enhance the emulsifying properties of sodium dodecylsulfate (SDS) based micellar system and thus making it appropriate for food applications. Exploration of interactions between the two species is the key constraint for execution of such ideas. In this work various micellar and thermodynamic parameters of SDS like critical micellar concentration (CMC), standard Gibbs free energy of micellization (ΔG(0)mic.) etc. have been calculated in different concentrations of disodium tartarate (DST) and trisodium citrate (TSC) in the temperature range (288.15-318.15)K from the conductivity and surface tension measurements. The parameters obtained from these studies reveal the competitive nature of both the additives with SDS for available positions at the air/water interface. TSC is found to be more effective additive in order to make SDS micellar system better for its potential applications as food emulsifier.

  8. Metal chelation therapy in rheumathoid arthritis: a case report. Successful management of rheumathoid arthritis by metal chelation therapy.

    PubMed

    Bamonti, Fabrizia; Fulgenzi, Alessandro; Novembrino, Cristina; Ferrero, Maria Elena

    2011-12-01

    Toxic metals are involved in the pathogenesis of some neurodegenerative and vascular diseases and are known to impair the immune system functions. We report here the case of a patient affected by heavy metal intoxication, who had developed an autoimmune disease. There was evidence of aluminium, cadmium and lead intoxication in a 63-year old Italian woman affected by rheumatoid arthritis (RA). We treated the patient with calcium disodium edetate (EDTA) once a week for a year in order to remove traces of heavy metal intoxication. Oxidative status profile was carried out at the beginning and after 6 months' EDTA chelation. At the end of the treatment, the patient did not show any signs of metal intoxication, RA symptoms and oxidative status improved.

  9. Assessment of boric acid and borax using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents

    SciTech Connect

    Moore, J.A.

    1995-03-01

    This document presents an evaluation of the reproductive and developmental effects of boric acid, H3BO3 (CAS Registry No. 10043-35-3) and disodium tetraborate decahydrate or borax, Na2B4O2O(CAS Registry No. 1303-96-4). The element, boron, does not exist naturally. In dilute aqueous solution and at physiological pH (7.4), the predominant species in undissociated boric acid (greater than 98%), irrespective of whether the initial material was boric acid of borax. Therefore, it is both useful and correct to compare exposures and dosages to boric acid and borax in terms of `boron equivalents`, since both materials form equivalent species in dilute aqueous solution with similar systemic effects. In order to be clear in this document, the term `boron` will refer to `boron equivalents` or percent boron in boric acid and borax.

  10. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    SciTech Connect

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai -Zhuang; Lin, Zijing; Zhu, Zi -Zhong; Ho, Kai -Ming

    2015-10-26

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. In addition, these structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.

  11. Photosensitized Reduction of Carbon Dioxide in Solution Using Noble-Metal Clusters for Electron Transfer

    NASA Astrophysics Data System (ADS)

    Toshima, Naoki; Yamaji, Yumi; Teranishi, Toshiharu; Yonezawa, Tetsu

    1995-03-01

    Carbon dioxide was reduced to methane by visible-light irradiation of a solution composed of tris(bipyridine)ruthenium(III) as photosensitizer, ethylenediaminetetraacetic acid disodium salt as sacrificial reagent, methyl viologen as electron relay, and a colloidal dispersion of polymer-protected noble-metal clusters, prepared by alcohol-reduction, as catalyst. Among the noble-metal clusters examined, Pt clusters showed the highest activity for the formation of methane as well as hydrogen. In order to improve the activity, oxidized clusters and bimetallic clusters were also applied. For example, the CH4 yield in 3-h irradiation increased from 51 x 10-3 μmol with unoxidized Pt clusters to 72 x 10-3 μmol with partially oxidized ones. In the case of Pt/Ru bimetalic systems, the improvement of the catalytic activity by air treatment was much greater than in case of monometallic clusters.

  12. A Food and Drug Administration-approved Asthma Therapeutic Agent Impacts Amyloid β in the Brain in a Transgenic Model of Alzheimer Disease*

    PubMed Central

    Hori, Yukiko; Takeda, Shuko; Cho, Hansang; Wegmann, Susanne; Shoup, Timothy M.; Takahashi, Kazue; Irimia, Daniel; Elmaleh, David R.; Hyman, Bradley T.; Hudry, Eloise

    2015-01-01

    Interfering with the assembly of Amyloid β (Aβ) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-Aβ-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of Aβ monomers into higher-order oligomers and fibrils in vitro without affecting Aβ production. In vivo, the levels of soluble Aβ are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble Aβ in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on Aβ economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease. PMID:25468905

  13. Crown ether-doped sol-gel materials for strontium(II) separation

    PubMed

    Yost; Fagan; Allain; Barnes; Dai; Sepaniak; Xue

    2000-11-01

    Hybrid organic/inorganic sol-gel materials containing an encapsulated crown ether ligand were found to selectively remove 91.4 +/- 1.3% of Sr2+ from a solution containing excess of competing ions such as Ca2+. The crown ether ligand, 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-7,16-bis(malonate) ligand (Na4oddm), with known high affinity for Sr2+ was encapsulated in hydrophilic SiO2 through a simple sol-gel process. Washing the Sr(2+)-loaded gel with acid or ethylenediaminetetraacetic acid disodium salt recovered the Sr2+ from the sol-gel sorbent and regenerated the doped gel for subsequent Sr2+ intake. The approach reported here is a new alternative to the use of crown ethers in metal ion separation through, for example, solvent extraction or the use of sorbents containing chemically grafted crown ether ligands. PMID:11080909

  14. Effect of Sodium Carboxymethyl Celluloses on Water-catalyzed Self-degradation of 200-degree C-heated Alkali-Activated Cement

    SciTech Connect

    Sugama T.; Pyatina, T.

    2012-05-01

    We investigated the usefulness of sodium carboxymethyl celluloses (CMC) in promoting self-degradation of 200°C-heated sodium silicate-activated slag/Class C fly ash cementitious material after contact with water. CMC emitted two major volatile compounds, CO2 and acetic acid, creating a porous structure in cement. CMC also reacted with NaOH from sodium silicate to form three water-insensitive solid reaction products, disodium glycolate salt, sodium glucosidic salt, and sodium bicarbonate. Other water-sensitive solid reaction products, such as sodium polysilicate and sodium carbonate, were derived from hydrolysates of sodium silicate. Dissolution of these products upon contact with water generated heat that promoted cement’s self-degradation. Thus, CMC of high molecular weight rendered two important features to the water-catalyzed self-degradation of heated cement: One was the high heat energy generated in exothermic reactions in cement; the other was the introduction of extensive porosity into cement.

  15. Gateways to clinical trials.

    PubMed

    Tomillero, A; Moral, M A

    2010-04-01

    Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, AMA1-C1/alhydrogel, Amlodipine besylate/atorvastatin calcium, Aripiprazole, Artesunate/amodiaquine, Asenapine maleate; Bosentan, Brivaracetam; Carisbamate, Clevudine, Clofarabine, Corticorelin acetate; Dasatinib; Elinogrel potassium, Entecavir, Erlotinib hydrochloride, Eslicarbazepine acetate, Etazolate; Fampridine, Fluarix, Fondaparinux sodium, Fulvestrant; Gabapentin enacarbil, GDC-0941, GI-5005, Golimumab; Imatinib mesylate, Lacosamide, Lapatinib ditosylate, Levetiracetam, Liraglutide, LOLA; Mecasermin, Morphine hydrochloride; Natalizumab, Nilotinib hydrochloride monohydrate; Olmesartan medoxomil, Omacetaxine mepesuccinate; Paclitaxel-eluting stent, Peginterferon alfa-2a, Peginterferon alfa-2b, Pemetrexed disodium, Poly I:CLC, Pralatrexate, Pregabalin; Ranolazine, Rasagiline mesilate, Retigabine hydrochloride, Rhenium Re-186 etidronate, Rosuvastatin calcium, Rotigotine, RTL-1000, Rufinamide; Sirolimus-eluting coronary stent, Sirolimus-eluting stent, Sorafenib, Stiripentol; Tiotropium bromide; Valsartan/amlodipine besylate, Varenicline tartrate; XL-184; Zoledronic acid monohydrate. PMID:20448862

  16. Effect of trace organic compounds on the corrosion of Cu/Ni alloys in sulfide polluted seawater

    SciTech Connect

    Reda, M.R.; Al-Hajji, J.N. )

    1993-05-01

    Trace organic complexing agents were investigated to check their ability to reduce the relatively high corrosion rates of Cu/Ni alloys in sulfide polluted seawater. It is found that an organic complexing agent such as fuchsin in the concentration range of 5 ppm is an excellent inhibitor against uniform and localized attack for 70/30 Cu/Ni alloy in 2 ppm sulfide polluted seawater. Another metal complexing agent, SSA (5-sulfosalicylic acid), was found to be effective for the 90/10 Cu/Ni alloy against enhanced attack by sulfide polluted seawater while it was ineffective for 70/30 Cu/Ni alloy. EDTA (ethylene diaminetetraacetic acid disodium salt) was found to be ineffective for both Cu/Ni alloys when used by itself in the concentration range of 5 ppm. A mechanism is proposed to explain the effectiveness of the various selected trace organic complexing agents on the corrosiveness of sulfide polluted seawater.

  17. Solvothermal synthesis of well-dispersed ZnSe microspheres.

    PubMed

    Ren, Xiaolei; Li, Qiuyu; Xue, Yannan; Zhai, Xuefeng; Yu, Min

    2013-01-01

    Well-defined crystalline ZnSe microspheres have been fabricated successfully via a simple solvothermal route under mild conditions in the presence of ethylenediamine tetraacetic acid disodium salt (Na(2)EDTA) and octadecylamine (ODA). X-ray powder diffraction (XRD), field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectrum (EDS), X-ray photoelectron spectra (XPS), Fourier transform-infrared spectroscopy (FT-IR), and photoluminescence spectra (PL) were used to characterize the phase structures, morphologies, and properties of the products. The result of XRD demonstrated that we obtained ZnSe products crystallized well with a stilleite structure. The influencing elements such as reaction time, sodium hydroxide (NaOH), addition of chelating reagent Na(2)EDTA, and the water/ethanol volume ratio were investigated, and the possible formation mechanism was also proposed. Furthermore, the experimental result indicated that ZnSe microspheres showed blue emission under ultraviolet excitation.

  18. Isolation and analysis of polysaccharide showing high hyaluronidase inhibitory activity in Nostochopsis lobatus MAC0804NAN.

    PubMed

    Yamaguchi, Yuji; Koketsu, Mamoru

    2016-03-01

    An active substance with high hyaluronidase inhibitory effect was isolated from the edible cyanobacterium Nostochopsis lobatus MAC0804NAN strain and characterized. The active component in the hot water extract was purified by anion exchange and gel filtration chromatography and was found to be a polysaccharide. The IC(50) against hyaluronidase of the purified polysaccharide was 7.18 μg/ml whose inhibitory activity is 14.5 times stronger than that of disodium cromoglycate (DSCG), an anti-allergy medication. The carbohydrate composition which was analyzed by GC-MS and NMR was found to be composed mainly of glucose, glucuronic acid, fucose, 2-O-methylfucose, mannose, galactose and xylose.

  19. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    PubMed Central

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai-Zhuang; Lin, Zijing; Zhu, Zi-Zhong; Ho, Kai-Ming

    2015-01-01

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. These structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs. PMID:26497381

  20. Studies on synthesis of alumina nanopowder from synthetic Bayer liquor

    SciTech Connect

    Mazloumi, Mahyar; Arami, Hamed; Khalifehzadeh, Razieh; Sadrnezhaad, S.K. . E-mail: sadrnezh@sharif.edu

    2007-06-05

    Procedure for synthesis of alumina nanopowder from Bayer liquor (synthetic sodium aluminate solution) is investigated. Cooling, ageing and then addition of 3 ml/l Tiron (1,2-dihydroxy-3,5-benzene disulfonic acid disodium salt) to the supersaturated liquor affect purity and fineness of the nanopowder product. X-ray diffraction (XRD), transmission electron microscopy (TEM), scanning electron microscopy (SEM) and energy dispersive X-ray (EDAX) analyses indicate that purity of the alumina nanopowder increases with the aging time. Experimental observations show that highly pure alumina nanopowders could be produced by direct calcination of cold gelatinous sodium aluminate solution followed by careful washing at a Tiron concentration of 3 ml/l NaOH.

  1. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    DOE PAGES

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai -Zhuang; Lin, Zijing; Zhu, Zi -Zhong; Ho, Kai -Ming

    2015-10-26

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. In addition, these structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been muchmore » less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.« less

  2. Determination of p-cresidine in FD&C red no. 40 by the diazotization and coupling procedure followed by reversed-phase high-performance liquid chromatography.

    PubMed

    Richfield-Fratz, N; Bailey, J E

    1987-09-18

    The free aromatic amine p-cresidine is determined at low ppb (10(9] levels in the regulated color additive FD&C Red No. 40. The determination involves chloroform extraction of p-cresidine and other unsulfonated impurities from the color additive, followed by diazotization of the aromatic amines and coupling with the disodium salt of 3-hydroxy-2,7-naphthalenedisulfonic acid (R-salt). The coupling products are then determined by reversed-phase high-performance liquid chromatography. Calibration is performed in the presence of the color additive by using the external standard method. The identity of the p-cresidine coupling product is confirmed by obtaining a UV-VIS spectrum of the eluting solute. The presence of aniline in commercial batches is also confirmed in this manner by using 4,5-dihydro-5-oxo-1-(4-sulfophenyl)-1H-pyrazole-3-carboxylic acid (pyrazolone-T) as an alternative coupling agent.

  3. [Structural analyses of unknown red dyes detected in dried strawberry].

    PubMed

    Shindo, Tetsuya; Sadamasu, Yuki; Suzuki, Keiko; Tanaka, Yasukazu; Togawa, Akiko; Nakajima, Junichi; Nakazato, Mitsuo; Uematsu, Yoko

    2012-01-01

    We examined two unknown red dyes (designated as red dyes "A" and "B") from a dried strawberry package with a label that indicated the presence of food red No. 40 (R40). Red dye "A" was identified as trisodium 3-hydroxy-4-[(2'-methoxy-5'-methyl-4'-sulfonatophenyl)azo]-2,7-naphthalenedisulfonate (CSA-R) by HPLC, UV-VIS spectra and MS spectra. This compound is one of the four reported subsidiary colors of R40. Detailed analyses of red dye "B" by MS and NMR demonstrated that its structure was disodium 3-hydroxy-4-[(2'-methoxy-5'-methyl-4'-sulfonatophenyl)azo]-2-naphthalenesulfonate. Red dye "B" is a structural isomer of R40, that has not been reported previously. Our results suggest that the two minor red dyes were subsidiary colors contained in R40, which had been added to the dried strawberries.

  4. DSCG binding protein and process for preparing same

    SciTech Connect

    Pecht, I.; Mazurek, N.

    1987-07-28

    An essentially pure protein is described consisting essentially of the protein, (CBP), present in nature in membranes of basophile cells and in mast cells, having a molecular weight of about 60,000 +- 2,000 determined by SDS polyacrylamide electrophoresis an isoelectric point of about 3.9 and an amino acid composition of about 4 units of asparagine, 3 units of threonine and serine, 3 units glycine, 2 units alanine, 2 units proline, 1 unit cysteine, 2 units valine, 1 unit methionine, 1 unit isoleucine, 2 units leucine, 1 unit tyrosine, 1 unit phenylalanine, 2 units histamine, 2 units lysine and 1 unit arginine. The protein is able to build calcium and having a calcium dependent affinity to the disodium salt of 1,2 bis(-2 carboxychromon-5-yloxy)-2-hydroxy propane (DSCG).

  5. Reduction to benzidine is not necessary for the covalent binding of a benzidine azodye to rat liver DNA.

    PubMed

    Kennelly, J C; Shaw, A; Martin, C N

    1984-09-28

    The DNA binding of 2 benzidine azodyes, Congo Red and Direct Blue 6, was compared in rat liver. Both dyes showed binding consequent upon metabolism to benzidine, and in each case hydrolysis of the liver DNA yielded N-(deoxyguanosin-8-yl)-N'-acetylbenzidine. The majority of Direct Blue 6-derived radioactivity bound to DNA was present as at least one other novel species. Our preliminary work on the major Direct Blue 6 DNA adduct suggests its structure may be disodium 8-amino-2-[4-(N-deoxyguanosin-8-yl)-aminobiphenyl-4'-yl] azo-1-hydroxynaphthalene-3,6-disulphonate. This adduct may form as a result of the susceptibility of the dye to hepatic azoreductase and its apparent existence may explain the observed potent carcinogenicity of dyes such as Direct Blue 6.

  6. Physicochemical properties of skim milk powders prepared with the addition of mineral chelators.

    PubMed

    Sikand, V; Tong, P S; Vink, Sean; Roy, Soma

    2016-06-01

    The objective of this study was to determine the effect of mineral chelator addition during skim milk powder (SMP) manufacture on the solubility, turbidity, soluble protein, and heat stability (HS). Three chelators (sodium citrate dihydrate, sodium polyphosphate, and disodium EDTA) at 3 different concentrations (5, 15, and 25mM) were added to skim milk concentrate (30% total solids), and the pH was adjusted to 6.65 before spray drying to produce SMP. Spray-dried SMP samples were tested for solubility index (SI). Additionally, samples were reconstituted to contain 9% total solids, adjusted to pH 7.0, and tested for turbidity, protein content from supernatants of ultracentrifuged samples, and HS. Lower SI values were observed for samples treated with 5mM disodium EDTA and sodium polyphosphate than control samples or samples with 5mM sodium citrate dihydrate. Furthermore, lower SI values were observed with an increased level of chelating agents regardless of chelator type. A decreased turbidity value was found with increasing levels of mineral chelating salt treatment. Low turbidity with increasing levels of added chelators may be associated with the dissociation of caseins from micelles. Furthermore, higher protein content was observed in supernatants of ultracentrifuged samples treated with increased level of chelators as compared with the control sample. Higher HS was observed in samples treated with 5mM compared with samples treated with 25mM mineral chelator. The results suggest improved solubility and HS upon addition of mineral chelators to SMP during its manufacture. PMID:27040785

  7. Organic anodes and sulfur/selenium cathodes for advanced Li and Na batteries

    NASA Astrophysics Data System (ADS)

    Luo, Chao

    To address energy crisis and environmental pollution induced by fossil fuels, there is an urgent demand to develop sustainable, renewable, environmental benign, low cost and high capacity energy storage devices to power electric vehicles and enhance clean energy approaches such as solar energy, wind energy and hydroenergy. However, the commercial Li-ion batteries cannot satisfy the critical requirements for next generation rechargeable batteries. The commercial electrode materials (graphite anode and LiCoO 2 cathode) are unsustainable, unrenewable and environmental harmful. Organic materials derived from biomasses are promising candidates for next generation rechargeable battery anodes due to their sustainability, renewability, environmental benignity and low cost. Driven by the high potential of organic materials for next generation batteries, I initiated a new research direction on exploring advanced organic compounds for Li-ion and Na-ion battery anodes. In my work, I employed croconic acid disodium salt and 2,5-Dihydroxy-1,4-benzoquinone disodium salt as models to investigate the effects of size and carbon coating on electrochemical performance for Li-ion and Na-ion batteries. The results demonstrate that the minimization of organic particle size into nano-scale and wrapping organic materials with graphene oxide can remarkably enhance the rate capability and cycling stability of organic anodes in both Li-ion and Na-ion batteries. To match with organic anodes, high capacity sulfur and selenium cathodes were also investigated. However, sulfur and selenium cathodes suffer from low electrical conductivity and shuttle reaction, which result in capacity fading and poor lifetime. To circumvent the drawbacks of sulfur and selenium, carbon matrixes such as mesoporous carbon, carbonized polyacrylonitrile and carbonized perylene-3, 4, 9, 10-tetracarboxylic dianhydride are employed to encapsulate sulfur, selenium and selenium sulfide. The resulting composites exhibit

  8. Chelant-assisted phytoextraction and accumulation of Zn by Zea mays.

    PubMed

    Gheju, M; Stelescu, I

    2013-10-15

    Zea mays plants were exposed to soils with concentrations of Zn ranging from 64 to 1800 mg kg(-1) dw, and the efficiency of three selected chelating agents (trisodium citrate (CI), disodium oxalate (OX) and disodium dihydrogen ethylene-diamine-tetraacetate (EDTA)) in enhancing metal phytoextraction was compared. Zn concentration in plant tissues increased in conjunction with the metal concentration of the soil. EDTA was found to be the most efficient chelating amendment, increasing concentrations of Zn in shoots from 88 mg kg(-1) dw, at 64 mg kg(-1) dw soil, to 8026 mg kg(-1) dw at 1800 mg kg(-1) dw soil. The overall orders of BCFs and TFs which resulted from this study are: EDTA > H2O > OX > CI, and EDTANa2 > OX > CI > H2O, respectively. The more effective uptake of Zn by plants for the control treatment (distilled water only) than for CI and OX was attributed to the neutral or slightly alkaline pH of the two chelant irrigation solutions. Instead, EDTA had a favorable effect on Zn uptake from soil due to its additive chelating and acidifying properties. Among the three chelants, only EDTA significantly increased the Zn phytoextraction potential of Z. mays, while CI and OX induced a low metal uptake from soil by plants. Although Z. mays has a lower Zn accumulation capacity than the hyperaccumulator Thlaspi caerulescens, it could be considered as a potential phytoremediator of soils with elevated Zn concentrations, especially when metal pollution extends to depths greater than 20 cm.

  9. A clinical comparison of two calculus-inhibiting dentifrices.

    PubMed

    Conforti, N; Berta, R; Petrone, M E; DeVizio, W; Volpe, A R; Proskin, H M

    2000-01-01

    The objective of this double-blind clinical study, conducted in harmony with the Volpe-Manhold design for studies of dental calculus, was to compare the effect on supragingival calculus formation of a dentifrice containing pyrophosphate, tripolyphosphate and a copolymer in a 0.243% sodium fluoride/silica base (Test Dentifrice), to that of a commercially available calculus-inhibiting dentifrice containing tetrapotassium pyrophosphate, disodium pyrophosphate and tetrasodium pyrophosphate in a 0.243% sodium fluoride/silica base (Positive Control Dentifrice). Adult male and female subjects from the Buffalo, New York area were entered into the study, provided a full oral prophylaxis, and assigned the use of a placebo (non-calculus-inhibiting) dentifrice for fourteen weeks. At the completion of this initial period, subjects were assessed for baseline Volpe-Manhold Calculus Index scores, provided another full prophylaxis, and stratified into two treatment groups which were balanced for age, sex and baseline calculus. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice, using a soft-bristled toothbrush. Examinations for dental calculus were again performed after twelve weeks' use of the study dentifrices. Ninety-one (91) subjects complied with the protocol and completed the entire study. At the three-month examination, the Test Dentifrice group exhibited a statistically significant 27.3% reduction in mean Volpe-Manhold Calculus Index score as compared to the Positive Control Dentifrice group. The results of this clinical study support the conclusion that a new calculus-inhibiting dentifrice, containing pyrophosphate, tripolyphosphate and a copolymer in a 0.243% sodium fluoride/silica base, is efficacious for the control of the development of supragingival calculus, and provides a level of benefit greater than that provided by a commercially available calculus-inhibiting dentifrice containing

  10. A calculus clinical study comparing the efficacy of two commercially available dentifrices.

    PubMed

    Sowinski, J; Battista, G; Petrone, D M; Petrone, M E; DeVizio, W; Volpe, A R; Proskin, H M

    2000-01-01

    The objective of this double-blind clinical study, conducted in harmony with the Volpe-Manhold design for studies of dental calculus, was to compare the effect on supragingival calculus formation of a dentifrice containing pyrophosphate, tripolyphosphate and a copolymer in a 0.243% sodium fluoride/silica base (Test Dentifrice), to that of a commercially available calculus-inhibiting dentifrice containing tetrapotassium pyrophosphate, disodium pyrophosphate, and tetrasodium pyrophosphate in a 0.243% sodium fluoride/silica base (Positive Control Dentifrice). Adult male and female subjects from the Northern New Jersey area were entered into the study, provided a full oral prophylaxis and assigned the use of a placebo (non-calculus-inhibiting) dentifrice for eight weeks. At the completion of this initial period, subjects were assessed for baseline Volpe-Manhold Calculus Index scores, provided another full prophylaxis and stratified into two treatment groups which were balanced for age, sex and baseline calculus. Subjects were instructed to brush their teeth twice daily (morning and evening) for one minute with their assigned dentifrice, using a soft-bristled toothbrush. Examinations for dental calculus were again performed after twelve weeks' use of the study dentifrices. Eighty-nine (89) subjects complied with the protocol and completed the entire study. At the three-month examination, the Test Dentifrice group exhibited a statistically significant 31.0% reduction in the mean Volpe-Manhold Calculus Index score compared to the Positive Control Dentifrice group. The results of this clinical study support the conclusion that a new calculus-inhibiting dentifrice containing pyrophosphate, tripolyphosphate, and a copolymer in a 0.243% sodium fluoride/silica base is efficacious for the control of the development of supragingival calculus, and provides a level of benefit greater than that provided by a commercially available calculus-inhibiting dentifrice containing

  11. A Novel High-Throughput Approach to Measure Hydroxyl Radicals Induced by Airborne Particulate Matter

    PubMed Central

    Son, Yeongkwon; Mishin, Vladimir; Welsh, William; Lu, Shou-En; Laskin, Jeffrey D.; Kipen, Howard; Meng, Qingyu

    2015-01-01

    Oxidative stress is one of the key mechanisms linking ambient particulate matter (PM) exposure with various adverse health effects. The oxidative potential of PM has been used to characterize the ability of PM induced oxidative stress. Hydroxyl radical (•OH) is the most destructive radical produced by PM. However, there is currently no high-throughput approach which can rapidly measure PM-induced •OH for a large number of samples with an automated system. This study evaluated four existing molecular probes (disodium terephthalate, 3′-p-(aminophenyl)fluorescein, coumarin-3-carboxylic acid, and sodium benzoate) for their applicability to measure •OH induced by PM in a high-throughput cell-free system using fluorescence techniques, based on both our experiments and on an assessment of the physicochemical properties of the probes reported in the literature. Disodium terephthalate (TPT) was the most applicable molecular probe to measure •OH induced by PM, due to its high solubility, high stability of the corresponding fluorescent product (i.e., 2-hydroxyterephthalic acid), high yield compared with the other molecular probes, and stable fluorescence intensity in a wide range of pH environments. TPT was applied in a high-throughput format to measure PM (NIST 1648a)-induced •OH, in phosphate buffered saline. The formed fluorescent product was measured at designated time points up to 2 h. The fluorescent product of TPT had a detection limit of 17.59 nM. The soluble fraction of PM contributed approximately 76.9% of the •OH induced by total PM, and the soluble metal ions of PM contributed 57.4% of the overall •OH formation. This study provides a promising cost-effective high-throughput method to measure •OH induced by PM on a routine basis. PMID:26516887

  12. Why the NIH Trial to Assess Chelation Therapy (TACT) Should Be Abandoned

    PubMed Central

    Atwood, Kimball C.; Woeckner, Elizabeth; Baratz, Robert S.; Sampson, Wallace I.

    2008-01-01

    The National Institutes of Health (NIH) Trial to Assess Chelation Therapy (TACT) was begun in 2003 and is expected to be completed in 2009. It is a trial of office-based, intravenous disodium ethylene-diamine-tetra-acetic acid (Na2EDTA) as a treatment for coronary artery disease (CAD). A few case series in the 1950s and early 1960s had found Na2EDTA to be ineffective for CAD or peripheral vascular disease (PVD). Nevertheless, a few hundred physicians, almost all of whom advocate other dubious treatments, continued to peddle chelation as an office treatment. They claim that chelation dramatically improves symptoms and prolongs life in 80% to 90% of patients. In response, academics performed 4 controlled trials during the 1990s. None favored chelation, but chelationists repudiated those findings. We have investigated the method and the trial. We present our findings in 4 parts: history, origin and nature of the TACT, state of the evidence, and risks. We present evidence that chelationists and their organization, the American College for Advancement in Medicine, used political connections to pressure the NIH to fund the TACT. The TACT protocols justified the trial by misrepresenting case series and by ignoring evidence of risks. The trial employs nearly 100 unfit co-investigators. It conflates disodium EDTA and another, somewhat safer drug. It lacks precautions necessary to minimize risks. The consent form reflects those shortcomings and fails to disclose apparent proprietary interests. The trial's outcome will be unreliable and almost certainly equivocal, thus defeating its stated purpose. We conclude that the TACT is unethical, dangerous, pointless, and wasteful. It should be abandoned. PMID:18596934

  13. Rheological properties of reversible thermo-setting in situ gelling solutions with the methylcellulose-polyethylene glycol-citric acid ternary system (2): Effects of various water-soluble polymers and salts on the gelling temperature.

    PubMed

    Shimokawa, Ken-ichi; Saegusa, Katsuhiko; Ishii, Fumiyoshi

    2009-11-01

    The influences of various salts and water-soluble polymers on the phase transition temperature of thermo-setting gels prepared by combining methylcellulose (MC)-sodium citrate (SC)-polyethylene glycol (PEG) at appropriate ratios (the MC-SC-PEG system) were investigated. Concerning cations, comparison of the phase transition temperature between SC and tripotassium citrate (PC) showed a rapid increase in the viscosity of SC between 20 degrees C and 25 degrees C and an increase in the viscosity of PC between 30 degrees C and 35 degrees C. Concerning the valency of anions, comparisons among SC, disodium tartrate dihydrate (ST), disodium maleate hemihydrates (SM), and sodium sulfate (SS) showed a rapid increase in the viscosity of trivalent SC between 20 degrees C and 25 degrees C and changes in the viscosity of the three bivalent sodium salts (ST, SM, and SS) at > or =30 degrees C. Thus the phase transition temperature decreased with an increase in the valency of anions. Subsequently, the influences of various water-soluble polymers on the gelling temperature were compared. Using polyvinylpyrrolidone (PVP) instead of PEG, the gelling temperature decreased with an increase in the PVP concentration even without the addition of SC. Unlike PVP, the addition of xanthan gum as a viscosity-increasing polysaccharide did not reduce the gelling temperature irrespective of its concentration. Temperature-associated changes in viscosity were observed at a fixed SC concentration with changes in the concentration of PVP or PEG. The gel phase transition temperature increased from 46 degrees C to 50 degrees C in gels not containing PVP or PEG. The viscosity did not differ between the addition of PVP or PEG at a low concentration and its absence. However, the viscosity clearly changed after the addition of each agent at a high concentration.

  14. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α–Mediated Apoptosis

    PubMed Central

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W.; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N.; Gonzalez, Frank J.

    2016-01-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics–pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factor α (TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics–pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL’s protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  15. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α-Mediated Apoptosis.

    PubMed

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N; Gonzalez, Frank J; Wang, Guangji; Hao, Haiping

    2016-05-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics-pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factorα(TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics-pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL's protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  16. Blockade of Gap Junction Hemichannel Suppresses Disease Progression in Mouse Models of Amyotrophic Lateral Sclerosis and Alzheimer's Disease

    PubMed Central

    Takeuchi, Hideyuki; Mizoguchi, Hiroyuki; Doi, Yukiko; Jin, Shijie; Noda, Mariko; Liang, Jianfeng; Li, Hua; Zhou, Yan; Mori, Rarami; Yasuoka, Satoko; Li, Endong; Parajuli, Bijay; Kawanokuchi, Jun; Sonobe, Yoshifumi; Sato, Jun; Yamanaka, Koji; Sobue, Gen; Mizuno, Tetsuya; Suzumura, Akio

    2011-01-01

    Background Glutamate released by activated microglia induces excitotoxic neuronal death, which likely contributes to non-cell autonomous neuronal death in neurodegenerative diseases, including amyotrophic lateral sclerosis and Alzheimer's disease. Although both blockade of glutamate receptors and inhibition of microglial activation are the therapeutic candidates for these neurodegenerative diseases, glutamate receptor blockers also perturbed physiological and essential glutamate signals, and inhibitors of microglial activation suppressed both neurotoxic/neuroprotective roles of microglia and hardly affected disease progression. We previously demonstrated that activated microglia release a large amount of glutamate specifically through gap junction hemichannel. Hence, blockade of gap junction hemichannel may be potentially beneficial in treatment of neurodegenerative diseases. Methods and Findings In this study, we generated a novel blood-brain barrier permeable gap junction hemichannel blocker based on glycyrrhetinic acid. We found that pharmacologic blockade of gap junction hemichannel inhibited excessive glutamate release from activated microglia in vitro and in vivo without producing notable toxicity. Blocking gap junction hemichannel significantly suppressed neuronal loss of the spinal cord and extended survival in transgenic mice carrying human superoxide dismutase 1 with G93A or G37R mutation as an amyotrophic lateral sclerosis mouse model. Moreover, blockade of gap junction hemichannel also significantly improved memory impairments without altering amyloid β deposition in double transgenic mice expressing human amyloid precursor protein with K595N and M596L mutations and presenilin 1 with A264E mutation as an Alzheimer's disease mouse model. Conclusions Our results suggest that gap junction hemichannel blockers may represent a new therapeutic strategy to target neurotoxic microglia specifically and prevent microglia-mediated neuronal death in various

  17. Role for electrical synapses in shaping the output of coupled peptidergic neurons from Lymnaea.

    PubMed

    Beekharry, Christopher C; Zhu, Guan Z; Magoski, Neil S

    2015-04-01

    Electrically coupled neurons communicate through channel assemblies called gap junctions, which mediate the transfer of current from one cell to another. Electrical synapses ensure spike synchronization and reliable transmission, which influences bursting patterns and firing frequency. The present study concerns an electrically coupled two-neuron network in the gastropod mollusc, Lymnaea stagnalis. The neurons, designated Visceral Dorsal 1 (VD1) and Right Parietal Dorsal 2 (RPD2), are peptidergic, innervate aspects of the cardio-respiratory system, and show strong coupling, such that they fire synchronously. Using dual sharp-electrode current-clamp recording and morphological staining in isolated brain preparations, the hypothesis that the electrical synapse is necessary for accurate network output was tested. We found that both cells make extensive projections within and out of the brain, including across the visceral-parietal connective, which links VD1 and RPD2. Cutting this connective uncoupled the neurons and disrupted the firing rate and pattern of RPD2 more than VD1, consistent with VD1 being the master and RPD2 the follower. The electrical synapse was inhibited by select gap junction blockers, with niflumic acid and 5-nitro-2-(3-phenylpropylamino) benzoic acid decreasing the VD1→RPD2 and RPD2→VD1 coupling coefficients, whereas carbenoxolone, α-glycyrrhetinic acid, meclofenamic acid, and quinine were ineffective. There was little-to-no impact on VD1↔RPD2 firing synchrony or frequency when coupling was reduced pharmacologically. However, in the presence of gap junction blockers, suppressing the activity of VD1 by prolonged hyperpolarization revealed a distinct, low-frequency firing pattern in RPD2. This suggests that strong electrical coupling is key to maintaining a synchronous output and proper firing rate.

  18. Anti-inflammatory effects of 27 selected terpenoid compounds tested through modulating Th1/Th2 cytokine secretion profiles using murine primary splenocytes.

    PubMed

    Ku, Chi-Mei; Lin, Jin-Yuarn

    2013-11-15

    This study investigated 27 selected terpenoid compounds, including 8 monoterpenoids, 7 sesqui-terpenoids, 3 di-terpenoids, 8 tri-terpenoids, and 1 tetra-terpenoid, for their Th1/Th2 immunomodulatory potential using mouse primary splenocytes. Changes in Th1 cytokines, including interleukin (IL)-2 and interferon (IFN)-γ, and Th2 cytokines, including IL-4, IL-5 and IL-10, secreted by terpenoid-treated splenocytes were measured using the ELISA method. The results showed that triptolide, a diterpenoid, was most cytotoxic, reflecting an IC50 value of 46nM. Eucalyptol, limonene, linalool, thymol, parthenolide, andrographolide, 18β-glycyrrhetinic acid, lupeol, ursolic acid and β-sitosterol showed a strong Th2-inclination and anti-inflammation potential in vitro. In addition, (-)-trans-caryophyllene, oridonin, triptolide, diosgenin, betulinic acid, escin, and β-sitosterol treatments significantly inhibited both IL-2 (Th1) and IL-10 (Th2) cytokine production at the same time, suggesting that these terpenoid compounds have an anti-inflammation potential through the inhibition of T-cell immune responses. Diosgenin treatments significantly increased IFN-γ secretion levels using mouse splenocytes, suggesting that diosgenin may be useful in treating a viral infection through the stimulation of IFN-γ production. Menthone, farnesol and oridonin treatments did not markedly increase IL-10/IL-2 (Th2/Th1) cytokine secretion ratios, suggesting that menthone, farnesol and oridonin may have a relative Th1-inclination property, compared to the other selected terpenoid compounds. The relative Th1-inclination property of menthone, farnesol and oridonin may be applied to improve Th2-skewed allergic diseases.

  19. Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion

    SciTech Connect

    Lu, Li; Song, Hui-Fang; Zhang, Wei-Guo; Liu, Xue-Qin; Zhu, Qian; Cheng, Xiao-Long; Yang, Gui-Jiao; Li, Ang; Xiao, Zhi-Cheng

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer Prolonged culture expansion retards proliferation and induces senescence of hBMSCs. Black-Right-Pointing-Pointer Reduced 20S proteasomal activity and expression potentially contribute to cell aging. Black-Right-Pointing-Pointer MG132-mediated 20S proteasomal inhibition induces senescence-like phenotype. Black-Right-Pointing-Pointer 18{alpha}-GA stimulates proteasomal activity and restores replicative senescence. Black-Right-Pointing-Pointer 18{alpha}-GA retains differentiation without affecting stem cell characterizations. -- Abstract: Human bone marrow stromal cells (hBMSCs) could be used in clinics as precursors of multiple cell lineages following proper induction. Such application is impeded by their characteristically short lifespan, together with the increasing loss of proliferation capability and progressive reduction of differentiation potential after the prolonged culture expansion. In the current study, we addressed the possible role of 20S proteasomes in this process. Consistent with prior reports, long-term in vitro expansion of hBMSCs decreased cell proliferation and increased replicative senescence, accompanied by reduced activity and expression of the catalytic subunits PSMB5 and PSMB1, and the 20S proteasome overall. Application of the proteasome inhibitor MG132 produced a senescence-like phenotype in early passages, whereas treating late-passage cells with 18{alpha}-glycyrrhetinic acid (18{alpha}-GA), an agonist of 20S proteasomes, delayed the senescence progress, enhancing the proliferation and recovering the capability of differentiation. The data demonstrate that activation of 20S proteasomes assists in counteracting replicative senescence of hBMSCs expanded in vitro.

  20. Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation.

    PubMed

    Yamada, Aya; Futagi, Masaharu; Fukumoto, Emiko; Saito, Kan; Yoshizaki, Keigo; Ishikawa, Masaki; Arakaki, Makiko; Hino, Ryoko; Sugawara, Yu; Ishikawa, Momoko; Naruse, Masahiro; Miyazaki, Kanako; Nakamura, Takashi; Fukumoto, Satoshi

    2016-01-01

    Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43(-/-) salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43(-/-) samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43(-/-) phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis.

  1. Pharmacological blockade of gap junctions induces repetitive surging of extracellular potassium within the locust CNS.

    PubMed

    Spong, Kristin E; Robertson, R Meldrum

    2013-10-01

    The maintenance of cellular ion homeostasis is crucial for optimal neural function and thus it is of great importance to understand its regulation. Glial cells are extensively coupled by gap junctions forming a network that is suggested to serve as a spatial buffer for potassium (K(+)) ions. We have investigated the role of glial spatial buffering in the regulation of extracellular K(+) concentration ([K(+)]o) within the locust metathoracic ganglion by pharmacologically inhibiting gap junctions. Using K(+)-sensitive microelectrodes, we measured [K(+)]o near the ventilatory neuropile while simultaneously recording the ventilatory rhythm as a model of neural circuit function. We found that blockade of gap junctions with either carbenoxolone (CBX), 18β-glycyrrhetinic acid (18β-GA) or meclofenamic acid (MFA) reliably induced repetitive [K(+)]o surges and caused a progressive impairment in the ability to maintain baseline [K(+)]o levels throughout the treatment period. We also show that a low dose of CBX that did not induce surging activity increased the vulnerability of locust neural tissue to spreading depression (SD) induced by Na(+)/K(+)-ATPase inhibition with ouabain. CBX pre-treatment increased the number of SD events induced by ouabain and hindered the recovery of [K(+)]o back to baseline levels between events. Our results suggest that glial spatial buffering through gap junctions plays an essential role in the regulation of [K(+)]o under normal conditions and also contributes to a component of [K(+)]o clearance following physiologically elevated levels of [K(+)]o. PMID:23916994

  2. Aspergillus niger Enhance Bioactive Compounds Biosynthesis As Well As Expression of Functional Genes in Adventitious Roots of Glycyrrhiza uralensis Fisch.

    PubMed

    Li, Jing; Wang, Juan; Li, Jinxin; Liu, Dahui; Li, Hongfa; Gao, Wenyuan; Li, Jianli; Liu, Shujie

    2016-02-01

    In the present study, the culture conditions for the accumulation of Glycyrrhiza uralensis adventitious root metabolites in balloon-type bubble bioreactors (BTBBs) have been optimized. The results of the culture showed that the best culture conditions were a cone angle of 90° bioreactor and 0.4-0.6-0.4-vvm aeration volume. Aspergillus niger can be used as a fungal elicitor to enhance the production of defense compounds in plants. With the addition of a fungal elicitor (derived from Aspergillus niger), the maximum accumulation of total flavonoids (16.12 mg g(-1)) and glycyrrhetinic acid (0.18 mg g(-1)) occurred at a dose of 400 mg L(-1) of Aspergillus niger resulting in a 3.47-fold and 1.8-fold increase over control roots. However, the highest concentration of polysaccharide (106.06 mg g(-1)) was achieved with a mixture of elicitors (Aspergillus niger and salicylic acid) added to the medium, resulting in a 1.09-fold increase over Aspergillus niger treatment alone. Electrospray ionization tandem mass spectrometry (ESI-MS(n)) analysis was performed, showing that seven compounds were present after treatment with the elicitors, including uralsaponin B, licorice saponin B2, liquiritin, and (3R)-vestitol, only identified in the mixed elicitor treatment group. It has also been found that elicitors (Aspergillus niger and salicylic acid) significantly upregulated the expression of the cinnamate 4-hydroxylase (C4H), β-amyrin synthase (β-AS), squalene epoxidase (SE) and a cytochrome P450 monooxygenase (CYP72A154) genes, which are involved in the biosynthesis of bioactive compounds, and increased superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activity. PMID:26490378

  3. An overview on antidiabetic medicinal plants having insulin mimetic property.

    PubMed

    Patel, D K; Prasad, S K; Kumar, R; Hemalatha, S

    2012-04-01

    Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.

  4. The mechanism of injury-induced intracellular calcium concentration oscillations in the endothelium of excised rat aorta.

    PubMed

    Berra-Romani, Roberto; Raqeeb, Abdul; Torres-Jácome, Julián; Guzman-Silva, Alejandro; Guerra, Germano; Tanzi, Franco; Moccia, Francesco

    2012-01-01

    Endothelial injury is the primary event that leads to a variety of severe vascular disorders. Mechanical injury elicits a Ca(2+) response in the endothelium of excised rat aorta, which comprises an initial Ca(2+) release from inositol-1,4,5-trisphosphate (InsP(3))-sensitive stores followed by a long-lasting decay phase due to Ca(2+) entry through uncoupled connexons. The Ca(2+) signal may also adopt an oscillatory pattern, the molecular underpinnings of which are unclear. In the light of the role played by Ca(2+) spiking in tissue regeneration, this study aimed to unveil the mechanisms underlying injury-induced Ca(2+) oscillations. The latter reversibly ceased upon removal of extracellular Ca(2+) or addition of the gap junction blockers heptanol, 18 α,β-glycyrrhetinic acid, La(3+) and Ni(2+), but were insensitive to BTP-2 and SKF 96365. The spiking response was abolished by inhibiting the Ca(2+) entry mode of the Na(+)/Ca(2+) exchanger (NCX). The InsP(3)-producing agonist ATP resumed Ca(2+) oscillations in silent cells, while the phospholipase C inhibitor U73122 suppressed them. Injury-induced Ca(2+) transients were prevented by the sarcoplasmic-endoplasmic reticulum calcium ATPase (SERCA) blockers thapsigargin and cyclopiazonic acid, while they were unaffected by suramin and genistein. These data show for the first time that the coordinated interplay between NCX-mediated Ca(2+) entry and InsP(3)-dependent Ca(2+) release contributes to injury-induced intracellular Ca(2+) concentration oscillations.

  5. Contribution of K(+) channels to endothelium-derived hypolarization-induced renal vasodilation in rats in vivo and in vitro.

    PubMed

    Rasmussen, Kasper Moller Boje; Braunstein, Thomas Hartig; Salomonsson, Max; Brasen, Jens Christian; Sorensen, Charlotte Mehlin

    2016-07-01

    We investigated the mechanisms behind the endothelial-derived hyperpolarization (EDH)-induced renal vasodilation in vivo and in vitro in rats. We assessed the role of Ca(2+)-activated K(+) channels and whether K(+) released from the endothelial cells activates inward rectifier K(+) (Kir) channels and/or the Na(+)/K(+)-ATPase. Also, involvement of renal myoendothelial gap junctions was evaluated in vitro. Isometric tension in rat renal interlobar arteries was measured using a wire myograph. Renal blood flow was measured in isoflurane anesthetized rats. The EDH response was defined as the ACh-induced vasodilation assessed after inhibition of nitric oxide synthase and cyclooxygenase using L-NAME and indomethacin, respectively. After inhibition of small conductance Ca(2+)-activated K(+) channels (SKCa) and intermediate conductance Ca(2+)-activated K(+) channels (IKCa) (by apamin and TRAM-34, respectively), the EDH response in vitro was strongly attenuated whereas the EDH response in vivo was not significantly reduced. Inhibition of Kir channels and Na(+)/K(+)-ATPases (by ouabain and Ba(2+), respectively) significantly attenuated renal vasorelaxation in vitro but did not affect the response in vivo. Inhibition of gap junctions in vitro using carbenoxolone or 18α-glycyrrhetinic acid significantly reduced the endothelial-derived hyperpolarization-induced vasorelaxation. We conclude that SKCa and IKCa channels are important for EDH-induced renal vasorelaxation in vitro. Activation of Kir channels and Na(+)/K(+)-ATPases plays a significant role in the renal vascular EDH response in vitro but not in vivo. The renal EDH response in vivo is complex and may consist of several overlapping mechanisms some of which remain obscure.

  6. Connexins form functional hemichannels in porcine ciliary epithelium

    PubMed Central

    Shahidullah, Mohammad; Delamere, Nicholas A

    2014-01-01

    The expression of connexins in the ciliary epithelium is consistent with gap junctions between the pigmented (PE) and nonpigmented ciliary epithelium (NPE) that form when connexon hemichannels from adjacent cells pair to form a channel. Here we present evidence that suggests undocked connexons may form functional hemichannels that permit exchange of substances between NPE and the aqueous humor. Intact porcine eyes were perfused via the ciliary artery and propidium iodide (PI) (MW 668) was added to the aqueous humor compartment as a tracer. After calcium-free solution containing PI was introduced into the aqueous humor compartment for 30 min, fluorescence microscopy revealed PI in the NPE cell layer. PI entry into the NPE was inhibited by calcium and by the connexin antagonist 18α-glycyrrhetinic acid (18-AGA). Studies also were carried out with cultured porcine NPE. Under normal conditions, little PI entered the cultured cells but calcium-free medium stimulated PI accumulation and the entry was inhibited by 18-AGA. In cells loaded with calcein (MW 622), calcium-free solution stimulated calcein exit. 18-AGA partially suppressed calcein exit in calcium-free medium. Connexin 43 and connexin 50 proteins were detected by western blot analysis in both native and cultured NPE. In the intact eye, immunolocalization studies revealed connexin 50 at the basolateral, aqueous humor-facing, margin of the NPE. In contrast, connexin 43 was observed at the junction of the PE and NPE layer and on the basolateral membrane of PE. The results point to functional hemichannels at the NPE basolateral surface. It is feasible that hemichannels might contribute to the transfer of substances between the ciliary epithelium cytoplasm and aqueous humor. PMID:24262135

  7. Effect of licorice on the reduction of body fat mass in healthy subjects.

    PubMed

    Armanini, D; De Palo, C B; Mattarello, M J; Spinella, P; Zaccaria, M; Ermolao, A; Palermo, M; Fiore, C; Sartorato, P; Francini-Pesenti, F; Karbowiak, I

    2003-07-01

    The history of licorice, as a medicinal plant, is very old and has been used in many societies throughout the millennia. The active principle, glycyrrhetinic acid, is responsible for sodium retention and hypertension, which is the most common side-effect. We show an effect of licorice in reducing body fat mass. We studied 15 normal-weight subjects (7 males, age 22-26 yr, and 8 females, age 21-26 yr), who consumed for 2 months 3.5 g a day of a commercial preparation of licorice. Body fat mass (BFM, expressed as percentage of total body weight, by skinfold thickness and by bioelectrical impedance analysis, BIA) and extracellular water (ECW, percentage of total body water, by BIA) were measured. Body mass index (BMI) did not change. ECW increased (males: 41.8+/-2.0 before vs 47.0+/-2.3 after, p<0.001; females: 48.2+/-1.4 before vs 49.4+/-2.1 after, p<0.05). BFM was reduced by licorice: (male: before 12.0+/-2.1 vs after 10.8+/-2.9%, p<0.02; female: before 24.9+/-5.1 vs after 22.1+/-5.4, p<0.02); plasma renin activity (PRA) and aldosterone were suppressed. Licorice was able to reduce body fat mass and to suppress aldosterone, without any change in BMI. Since the subjects were consuming the same amount of calories during the study, we suggest that licorice can reduce fat by inhibiting 11beta-hydroxysteroid dehydrogenase Type 1 at the level of fat cells. PMID:14594116

  8. Connexins form functional hemichannels in porcine ciliary epithelium.

    PubMed

    Shahidullah, Mohammad; Delamere, Nicholas A

    2014-01-01

    The expression of connexins in the ciliary epithelium is consistent with gap junctions between the pigmented (PE) and nonpigmented ciliary epithelium (NPE) that form when connexon hemichannels from adjacent cells pair to form a channel. Here we present evidence that suggests undocked connexons may form functional hemichannels that permit exchange of substances between NPE and the aqueous humor. Intact porcine eyes were perfused via the ciliary artery and propidium iodide (PI) (MW 668) was added to the aqueous humor compartment as a tracer. After calcium-free solution containing PI was introduced into the aqueous humor compartment for 30 min, fluorescence microscopy revealed PI in the NPE cell layer. PI entry into the NPE was inhibited by calcium and by the connexin antagonist 18α-glycyrrhetinic acid (18-AGA). Studies also were carried out with cultured porcine NPE. Under normal conditions, little PI entered the cultured cells but calcium-free medium stimulated PI accumulation and the entry was inhibited by 18-AGA. In cells loaded with calcein (MW 622), calcium-free solution stimulated calcein exit. 18-AGA partially suppressed calcein exit in calcium-free medium. Connexin 43 and connexin 50 proteins were detected by western blot analysis in both native and cultured NPE. In the intact eye, immunolocalization studies revealed connexin 50 at the basolateral, aqueous humor-facing, margin of the NPE. In contrast, connexin 43 was observed at the junction of the PE and NPE layer and on the basolateral membrane of PE. The results point to functional hemichannels at the NPE basolateral surface. It is feasible that hemichannels might contribute to the transfer of substances between the ciliary epithelium cytoplasm and aqueous humor.

  9. An overview on antidiabetic medicinal plants having insulin mimetic property

    PubMed Central

    Patel, DK; Prasad, SK; Kumar, R; Hemalatha, S

    2012-01-01

    Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles. PMID:23569923

  10. Loss of responsiveness of circular smooth muscle cells from the guinea pig ileum is associated with changes in gap junction coupling.

    PubMed

    Carbone, Simona E; Wattchow, David A; Spencer, Nick J; Brookes, Simon J H

    2012-06-15

    Gap junction coupling and neuromuscular transmission to smooth muscle were studied in the first 4 h after preparations were set up in vitro. Intracellular recordings were made from smooth muscle cells of guinea pig ileum. Fast inhibitory junction potentials (IJPs) were small (1.3 ± 1.0 mV) in the first 30 min but increased significantly over the first 120 min to 15.8 ± 0.9 mV (n = 12, P < 0.001). Comparable increases in slow IJPs and excitatory junction potentials were also observed. During the same period, resting membrane potential depolarized from -58.8 ± 1.4 to -47.2 ± 0.4 mV (n = 12, P < 0.001). Input resistance, estimated by intracellular current injection, decreased in parallel (P < 0.05), and dye coupling, measured by intracellular injection of carboxyfluorescein, increased (P < 0.001). Input resistance was higher and dye coupling was less in longitudinal than circular smooth muscle cells. Gap junction blockers [carbenoxolone (100 μM), 18β-glycyrrhetinic acid (10 μM), and 2-aminoethoxydiphenyl borate (50 μM)] hyperpolarized coupled circular smooth muscle cells, reduced the amplitude of fast and slow IJPs and excitatory junction potentials, increased input resistance, and reduced dye coupling. Local application of ATP (10 mM) mimicked IJPs and showed comparable increases in amplitude over the first 120 min; carbenoxolone and 2-aminoethoxydiphenyl borate significantly reduced ATP-evoked hyperpolarizations in coupled cells. In contrast, synaptic transmission between myenteric neurons was not suppressed during the first 30 min. Gap junction coupling between circular smooth muscle cells in isolated preparations was initially disrupted but recovered over the next 120 min to a steady level. This was associated with potent effects on neuromuscular transmission and responses to exogenous ATP.

  11. Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

    PubMed

    Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

    2014-01-01

    To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible.

  12. Effects of diammonium glycyrrhizinate on random skin flap survival in rats: An experimental study

    PubMed Central

    Lv, Qing-Bo; Gao, Xiang; Lin, Ding-Sheng; Chen, Yun; Cao, Bin; Zhou, Kai-Liang

    2016-01-01

    Partial necrosis of skin flaps continues to restrict the survival of local skin flaps following plastic and reconstructive surgeries. The aim of the present study was to investigate the effects of diammonium glycyrrhizinate (DG), a salt of glycyrrhetinic acid that has been widely used in the therapy of chronic hepatitis and human immunodeficiency virus infection, on random skin flap survival in rats. McFarlane flaps were established in 60 male Sprague-Dawley rats randomly divided into three groups. Group I served as the control group and was injected with saline (10 mg/kg) once per day. Group II and group III were the experimental groups, and were injected with 10 mg/kg DG once and twice per day, respectively. On day 7, the survival area of the flap was measured. Tissue samples were stained with hematoxylin and eosin and immunohistochemically evaluated. Tissue edema, neutrophil density, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were evaluated. The mean survival areas of the flaps of group II were significantly larger when compared with those of group I (P<0.05), and the rats of group III exhibited significantly higher survival areas than group II (P<0.05). Histologic and immunohistochemical evaluation showed that microvessel development and the expression level of vascular endothelial growth factor were higher in the two experimental groups than in the control group. Furthermore, SOD activity was significantly increased (P<0.05), while the neutrophil density and MDA level were significantly reduced (P<0.05) in group II when compared with group I. Significant differences between group II and group III with regard to SOD activity and MDA level were also observed (P<0.05). Thus, DG may have a dose-dependent effect on promoting the survival of random skin flaps. PMID:27588181

  13. Carbenoxolone prevents the development of fatty liver in C57BL/6-Lep ob/ob mice via the inhibition of sterol regulatory element binding protein-1c activity and apoptosis.

    PubMed

    Rhee, Sang Dal; Kim, Chi-Hyun; Park, Ji Seon; Jung, Won Hoon; Park, Sung Bum; Kim, Hee Youn; Bae, Gyu Hwan; Kim, Ta Jan; Kim, Ki Young

    2012-09-15

    Carbenoxolone is the 3-hemisuccinate of glycyrrhetinic acid, the active principal of licorice (Glycyrrhiza glabra). It was reported that carbenoxolone improved glucose tolerance with increased insulin sensitivity in mice with high fat diet-induced obesity. In the present study, we elucidated the protective effect of carbenoxolone in fatty liver animal models of C57BL/6-Lep(ob/ob) mice through inhibition of hepatic lipogenesis and apoptosis. In addition, the potential mechanisms by which carbenoxolone could exert such protection were elucidated. Carbenoxolone was daily administrated by gavage for 28 days in C57BL/6 and C57BL/6-Lep(ob/ob) mice. Carbenoxolone prevented the plasma triglyceride and free fatty acid accumulation associated with the reduction of the expression of sterol regulatory element binding protein-1c, liver X receptor, fatty acid synthase and acethyl-CoA carboxylase in the livers of C57BL/6-Lep(ob/ob) mice. Carbenoxolone also prevented hepatic injury through anti-apoptotic action in the livers of C57BL/6-Lep(ob/ob) mice, accompanied by increased Bcl-2 expression and suppressed Bax and cytochrome c expression. As a mechanism, increased inflammatory cytokine expressions were inhibited by carbenoxolone in the fatty livers of C57BL/6-Lep(ob/ob) mice. Furthermore, carbenoxolone inhibited free fatty acid (oleate/palmitate) induced reactive oxygen species formation and reversed free fatty acid induced mitochondrial membrane depolarization in HepG2 cells. Carbenoxolone prevents the development of fatty liver by inhibiting sterol regulatory element binding protein-1c expression and activity with an anti-apoptotic mechanism via the inhibition of inflammatory cytokine and reactive oxygen species formation in the livers of C57BL/6-Lep(ob/ob) mice. It is suggested that carbenoxolone prevents the development and progression of fatty liver disease in patients with insulin resistance.

  14. Mechanisms contributing to cluster formation in the inferior olivary nucleus in brainstem slices from postnatal mice

    PubMed Central

    Kølvraa, Mathias; Müller, Felix C; Jahnsen, Henrik; Rekling, Jens C

    2014-01-01

    Abstract The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5–P15.5) spontaneously generates clusters of neurons with synchronous calcium transients, and intracellular recordings from IO neurons suggest that electrical coupling between neighbouring IO neurons may serve as a synchronizing mechanism. Here, we studied the cluster-forming mechanism and find that clusters overlap extensively with an overlap distribution that resembles the distribution for a random overlap model. The average somatodendritic field size of single curly IO neurons was ∼6400 μm2, which is slightly smaller than the average IO cluster size. Eighty-seven neurons with overlapping dendrites were estimated to be contained in the principal olive mean cluster size, and about six non-overlapping curly IO neurons could be contained within the largest clusters. Clusters could also be induced by iontophoresis with glutamate. Induced clusters were inhibited by tetrodotoxin, carbenoxelone and 18β-glycyrrhetinic acid, suggesting that sodium action potentials and electrical coupling are involved in glutamate-induced cluster formation, which could also be induced by activation of N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Spikelets and a small transient depolarizing response were observed during glutamate-induced cluster formation. Calcium transients spread with decreasing velocity during cluster formation, and somatic action potentials and cluster formation are accompanied by large dendritic calcium transients. In conclusion, cluster formation depends on gap junctions, sodium action potentials and spontaneous clusters occur randomly throughout the IO. The relative slow signal spread during cluster formation, combined with a strong dendritic influx of calcium, may signify that active dendritic properties contribute to cluster formation. PMID:24042500

  15. Connexin43 Hemichannels Mediate Small Molecule Exchange between Chondrocytes and Matrix in Biomechanically-Stimulated Temporomandibular Joint Cartilage

    PubMed Central

    Zhang, Jing; Zhang, Hongyun; Zhang, Mian; Qiu, Zhongying; Wu, Yaoping; Callaway, Danielle A.; Jiang, Jean X.; Lu, Lei; Jing, Lei; Yang, Ting; Wang, Meiqing

    2015-01-01

    Objective Connexin (Cx) 43 hemichannels play a role in mechanotransduction. This study was undertaken in order to determine if Cx43 hemichannels were activated in rat temporomandibular joint (TMJ) chondrocytes under mechanical stimulation. Methods Sprague-Dawley rats were stimulated dental-mechanically. Cx43 expression in rat TMJ cartilage was determined with immunohistochemistry and real-time PCR, and Cx43 hemichannel opening was evaluated by the extra- and intracellular levels of prostaglandin E2 (PGE2). Both primary rat chondrocytes and ATDC5 cells were treated with fluid flow shear stress (FFSS) to induce hemichannel opening. The Cx43 expression level was then determined by real-time PCR or western blotting, and the extent of Cx43 hemichannel opening was evaluated by measuring both PGE2 release and cellular dye uptake. Results Cx43 expression and intra- and extracellular PGE2 levels were increased in mechanically-stimulated rat TMJ cartilage compared to the unstimulated control. The FFSS treatment increased Cx43 expression and induced Cx43 hemichannel opening in primary rat chondrocytes and ATDC5 cells indicated by enhanced PGE2 release and dye uptake. Furthermore, the Cx43 hemichannel opening could be blocked by the addition of 18β-glycyrrhetinic acid, a connexin channel inhibitor, Cx43-targeting siRNA, or by withdrawal of FFSS stimulation. The migration of cytosolic Cx43 protein to the plasma membrane in ATDC5 cells was still significant after 8h post 2-h FFSS treatment, and the Cx43 protein level was still high at 48h which returned to control levels at 72h after treatment. Conclusion Cx43 hemichannels are activated and mediate small molecule exchange between TMJ chondrocytes and matrix under mechanical stimulation. PMID:24704497

  16. Mechanisms contributing to cluster formation in the inferior olivary nucleus in brainstem slices from postnatal mice.

    PubMed

    Kølvraa, Mathias; Müller, Felix C; Jahnsen, Henrik; Rekling, Jens C

    2014-01-01

    The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5-P15.5) spontaneously generates clusters of neurons with synchronous calcium transients, and intracellular recordings from IO neurons suggest that electrical coupling between neighbouring IO neurons may serve as a synchronizing mechanism. Here, we studied the cluster-forming mechanism and find that clusters overlap extensively with an overlap distribution that resembles the distribution for a random overlap model. The average somatodendritic field size of single curly IO neurons was ∼6400 μm(2), which is slightly smaller than the average IO cluster size. Eighty-seven neurons with overlapping dendrites were estimated to be contained in the principal olive mean cluster size, and about six non-overlapping curly IO neurons could be contained within the largest clusters. Clusters could also be induced by iontophoresis with glutamate. Induced clusters were inhibited by tetrodotoxin, carbenoxelone and 18β-glycyrrhetinic acid, suggesting that sodium action potentials and electrical coupling are involved in glutamate-induced cluster formation, which could also be induced by activation of N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Spikelets and a small transient depolarizing response were observed during glutamate-induced cluster formation. Calcium transients spread with decreasing velocity during cluster formation, and somatic action potentials and cluster formation are accompanied by large dendritic calcium transients. In conclusion, cluster formation depends on gap junctions, sodium action potentials and spontaneous clusters occur randomly throughout the IO. The relative slow signal spread during cluster formation, combined with a strong dendritic influx of calcium, may signify that active dendritic properties contribute to cluster formation.

  17. Role of gap junctions and protein kinase A during the development of oocyte maturational competence in Ayu (Plecoglossus altivelis)

    USGS Publications Warehouse

    Yamamoto, Y.; Yoshizaki, G.; Takeuchi, T.; Soyano, K.; Patino, R.

    2008-01-01

    Meiotic resumption in teleost oocytes is induced by a maturation-inducing hormone (MIH). The sensitivity of oocytes to MIH, also known as oocyte maturational competence (OMC), is induced by LH via mechanisms that are not fully understood. A previous study of Ayu (Plecoglossus altivelis) showed the presence of functional heterologous gap junctions (GJs) between oocytes and their surrounding granulosa cells. The objectives of this study were to determine the role of ovarian GJs and of protein kinase A (PKA) during the acquisition of OMC. We examined the effects of the specific GJ inhibitor carbenoxolone (CBX) and 18??-glycyrrhetinic acid (??-GA) on the LH-(hCG)-dependent acquisition of OMC and on MIH-(17,20??-dihydroxy-4-pregnen-3-one)-dependent meiotic resumption; measured the cAMP content of ovarian follicles during the hCG-dependent acquisition of OMC; and determined the effects of PK activators and inhibitors on hCG-dependent OMC. Production of follicular cAMP increased during the hCG-dependent acquisition of OMC. Both GJ inhibitors and the PKA inhibitor H8-dihydrochloride, but not the PKC inhibitor GF109203X, suppressed the hCG-dependent acquisition of OMC in a dose-dependent manner. The PKA activator forskolin induced OMC with a similar potency to hCG. Unlike previous observations with teleosts where disruption of heterologous GJ either blocks or stimulates meiotic resumption, treatment with GJ inhibitors did not affect MIH-dependent meiotic resumption in maturationally competent follicles of Ayu. These observations suggest that ovarian GJs are essential for LH-dependent acquisition of OMC but not for MIH-dependent meiotic resumption, and that the stimulation of OMC by LH is mediated by cAMP-dependent PKA. They are also consistent with the view that a precise balance between GJ-mediated signals (positive or negative) and oocyte maturational readiness is required for hormonally regulated meiotic resumption. ?? 2007 Elsevier Inc. All rights reserved.

  18. Retrovirus-mediated transfer of the herpes simplex virus thymidine kinase and connexin26 genes in pancreatic cells results in variable efficiency on the bystander killing: implications for gene therapy.

    PubMed

    Carrió, M; Mazo, A; López-Iglesias, C; Estivill, X; Fillat, C

    2001-10-01

    Currently, there is no effective treatment for pancreatic cancer and prodrug-activating gene therapy with the herpes simplex virus thymidine kinase gene (HSV-tk) in combination with ganciclovir (GCV) has been suggested as a candidate approach against this disease. In the present study, we have evaluated the efficacy of the HSV-tk/GCV treatment in a panel of pancreatic tumor cells (NP-9, NP-18, NP-31) and the potentiation of the cytotoxic effect in combination with the overexpression of the connexin 26 gene (Cx26). Pancreatic cells transduced with a retrovirus containing the HSV-tk gene showed different sensitivities to GCV that seemed to be independent of HSV-tk expression levels. The extent of the bystander effect also varied among the pancreatic tumor cells and correlated with the level of gap junction intercellular communication (GJIC). Transduction of the pancreatic tumor cells with a retrovirus carrying the connexin 26 gene resulted in high levels of connexin 26 expression and in an increase in the GJIC that correlated to an extent in the bystander effect in both NP-9Cx26 and NP-18Cx26 cells. Neither an increment in GJIC nor an increase in the bystander killing was detected in NP-31Cx26. The bystander effect in NP-18 Cx26 cells was also prevented by the long term inhibitor of GJIC, 18-alpha-glycyrrhetinic acid (AGA). Together, these results demonstrate that pancreatic tumor cells are highly different as regards the susceptibility to HSV-tk/GCV treatment. Moreover, they indicate that overexpression of the Cx26 gene does not always correspond to an increase in GJIC although they clearly suggest the role of GJIC in mediating the bystander effect.

  19. Yokukansan inhibits morphine tolerance and physical dependence in mice: the role of α₂A-adrenoceptor.

    PubMed

    Nakagawa, T; Nagayasu, K; Nishitani, N; Shirakawa, H; Sekiguchi, K; Ikarashi, Y; Kase, Y; Kaneko, S

    2012-12-27

    Yokukansan (YKS) is a traditional Japanese medicine consisting of seven medicinal herbs that is used for the treatment of neurosis, insomnia, and the behavioral/psychological symptoms of dementia. This study examined the effects of YKS on morphine tolerance and physical dependence in mice. Daily oral administration of YKS (0.5 or 1.0 g/kg) for 3 weeks significantly attenuated morphine tolerance and naloxone-precipitated morphine withdrawal signs (jumps and body weight loss) without affecting the analgesic effect of morphine. The inhibitory effect of YKS on withdrawal jumps in morphine-dependent mice was blocked by a single pretreatment with an α(2)-adrenoceptor antagonist, yohimbine, but not by an α(1)-adrenoceptor antagonist, prazosin. A similar inhibitory effect on withdrawal jumps was observed by repeated administration of yohimbine. The membrane expression of α(2A)-adrenoceptors in the pons/medulla was decreased in morphine withdrawn animals; this reduction was prevented by repeated administration of YKS or yohimbine. Competitive radioligand and [(35)S]guanosine-5'-O-(3-thiotriphosphate) binding assays revealed that YKS and its constituent herbs, Glycyrrhiza (GR) and Uncaria hook (UH), had specific binding affinity for and antagonist activity against the α(2A)-adrenoceptor. Certain chemical constituents, including GR -derived glycyrrhizin and its metabolite, 18β-glycyrrhetinic acid, and UH-derived geissoschizine methyl ether (GME), shared such activities. Repeated administration of GR, UH, glycyrrhizin or GME significantly inhibited morphine withdrawal signs. These results suggest that YKS and its active constituents inhibit morphine tolerance and physical dependence, and that the latter is due at least in part to the prevention of the decreased membrane expression of the α(2A)-adrenoceptor in the brainstem by its prolonged blockade. PMID:23069764

  20. Studies on preparation of medium fat liquid dairy whitener from buffalo milk employing ultrafiltration process.

    PubMed

    Khatkar, Sunil Kumar; Gupta, Vijay Kumar; Khatkar, Anju Boora

    2014-09-01

    A study was conducted to develop good quality medium fat liquid dairy whitener from buffalo milk employing ultrafiltration (UF) process. The buffalo skim milk was UF concentrated to 4.05 to 4.18 (23.63 ± 0.30 % TS) fold and standardized to 10 % fat (on Dry Matter Basis) (i.e. formulation) and homogenized at 175.76 kg/cm(2). The addition of 0.4 % mixture of monosodium and disodium phosphate (2:1 w/w) improved the heat stability of homogenized formulation to an optimum of 66 min. The bland flavour of homogenized formulation with added 0.4 % mixture of monosodium phosphate and disodium phosphate (2:1 w/w) and 18 % sugar (on DMB) (i.e. medium fat liquid dairy whitener) was improved significantly (P < 0.01) with the addition of 0.2 % potassium chloride, but heat stability of medium fat liquid dairy whitener got reduced substantially (i.e. 19 min). With subsequent heat treatment to 85 °C for 5 min, heat stability of medium fat liquid dairy whitener got improved to reasonable level of 27 min. Whitening ability in terms of L* value of medium fat liquid dairy whitener in both tea and coffee was significantly (P < 0.01) better when homogenized at 175.76 kg/cm(2) vis-à-vis 140.61 kg/cm(2). Standardized medium fat liquid dairy whitener had significantly (P < 0.01) greater protein content (i.e. approximately 2.43 times) compared to market dairy whitener samples. At 2 % solids level, standardized medium fat liquid dairy whitener in tea/coffee fetched significantly (P < 0.01) better sensory attributes and instrumental whitening ability compared to market sample at 3 % solids level. There could be clear 33 % solids quantity saving in case of developed product compared to market dairy whitener sample.

  1. Phase transitions in freeze-dried systems - quantification using in situ synchrotron X-ray diffractometry

    SciTech Connect

    Varshney, Dushyant B.; Sundaramurthi, Prakash; Kumar, Satyendra; Shalaev, Evgenyi Y.; Kang, Shin-Woong; Gatlin, Larry A.; Suryanarayanan, Raj

    2009-09-02

    The purpose is: (1) To develop a synchrotron X-ray diffraction (SXRD) method to monitor phase transitions during the entire freeze-drying cycle. Aqueous sodium phosphate buffered glycine solutions with initial glycine to buffer molar ratios of 1:3 (17:50 mM), 1:1 (50 mM) and 3:1 were utilized as model systems. (2) To investigate the effect of initial solute concentration on the crystallization of glycine and phosphate buffer salt during lyophilization. Phosphate buffered glycine solutions were placed in a custom-designed sample cell for freeze-drying. The sample cell, covered with a stainless steel dome with a beryllium window, was placed on a stage capable of controlled cooling and vacuum drying. The samples were cooled to -50 C and annealed at -20 C. They underwent primary drying at -25 C under vacuum until ice sublimation was complete and secondary drying from 0 to 25 C. At different stages of the freeze-drying cycle, the samples were periodically exposed to synchrotron X-ray radiation. An image plate detector was used to obtain time-resolved two-dimensional SXRD patterns. The ice, {beta}-glycine and DHPD phases were identified based on their unique X-ray peaks. When the solutions were cooled and annealed, ice formation was followed by crystallization of disodium hydrogen phosphate dodecahydrate (DHPD). In the primary drying stage, a significant increase in DHPD crystallization followed by incomplete dehydration to amorphous disodium hydrogen phosphate was evident. Complete dehydration of DHPD occurred during secondary drying. Glycine crystallization was inhibited throughout freeze-drying when the initial buffer concentration (1:3 glycine to buffer) was higher than that of glycine. A high-intensity X-ray diffraction method was developed to monitor the phase transitions during the entire freeze-drying cycle. The high sensitivity of SXRD allowed us to monitor all the crystalline phases simultaneously. While DHPD crystallizes in frozen solution, it dehydrates

  2. The influence of oxalate-promoted growth of saponite and talc crystals

    USGS Publications Warehouse

    Schumann, Dirk; Hartman, Hyman; Eberl, Dennis D.; Sears, S. Kelly; Hesse, Reinhard; Vali, Hojatollah

    2013-01-01

    The intercalating growth of new silicate layers or metal hydroxide layers in the interlayer space of other clay minerals is known from various mixed-layer clay minerals such as illite-smectite (I-S), chlorite-vermiculite, and mica-vermiculite. In a recent study, the present authors proposed that smectite-group minerals can be synthesized from solution as new 2:1 silicate layers within the low-charge interlayers of rectorite. That study showed how oxalate catalyzes the crystallization of saponite from a silicate gel at low temperatures (60ºC) and ambient pressure. As an extension of this work the aim of the present study was to test the claim that new 2:1 silicate layers can be synthesized as new intercalating layers in the low-charge interlayers of rectorite and whether oxalate could promote such an intercalation synthesis. Two experiments were conducted at 60ºC and atmospheric pressure. First, disodium oxalate solution was added to a suspension of rectorite in order to investigate the effects that oxalate anions have on the structure of rectorite. In a second experiment, silicate gel of saponitic composition (calculated interlayer charge −0.33 eq/O10(OH)2) was mixed with a suspension of rectorite and incubated in disodium oxalate solution. The synthesis products were extracted after 3 months and analyzed by X-ray diffraction and high-resolution transmission electron microscopy (HRTEM). The treatment of ultrathin sections with octadecylammonium (nC = 18) cations revealed the presence of 2:1 layer silicates with different interlayer charges that grew from the silicate gel. The oxalate-promoted nucleation of saponite and talc crystallites on the rectorite led to the alteration and ultimately to the destruction of the rectorite structure. The change was documented in HRTEM lattice-fringe images. The crystallization of new 2:1 layer silicates also occurred within the expandable interlayers of rectorite but not as new 2:1 silicate layers parallel to the previous 2

  3. Mitigation of Hydrogen Gas Generation from the Reaction of Water with Uranium Metal in K Basins Sludge

    SciTech Connect

    Sinkov, Sergey I.; Delegard, Calvin H.; Schmidt, Andrew J.

    2010-01-29

    Means to decrease the rate of hydrogen gas generation from the chemical reaction of uranium metal with water were identified by surveying the technical literature. The underlying chemistry and potential side reactions were explored by conducting 61 principal experiments. Several methods achieved significant hydrogen gas generation rate mitigation. Gas-generating side reactions from interactions of organics or sludge constituents with mitigating agents were observed. Further testing is recommended to develop deeper knowledge of the underlying chemistry and to advance the technology aturation level. Uranium metal reacts with water in K Basin sludge to form uranium hydride (UH3), uranium dioxide or uraninite (UO2), and diatomic hydrogen (H2). Mechanistic studies show that hydrogen radicals (H·) and UH3 serve as intermediates in the reaction of uranium metal with water to produce H2 and UO2. Because H2 is flammable, its release into the gas phase above K Basin sludge during sludge storage, processing, immobilization, shipment, and disposal is a concern to the safety of those operations. Findings from the technical literature and from experimental investigations with simple chemical systems (including uranium metal in water), in the presence of individual sludge simulant components, with complete sludge simulants, and with actual K Basin sludge are presented in this report. Based on the literature review and intermediate lab test results, sodium nitrate, sodium nitrite, Nochar Acid Bond N960, disodium hydrogen phosphate, and hexavalent uranium [U(VI)] were tested for their effects in decreasing the rate of hydrogen generation from the reaction of uranium metal with water. Nitrate and nitrite each were effective, decreasing hydrogen generation rates in actual sludge by factors of about 100 to 1000 when used at 0.5 molar (M) concentrations. Higher attenuation factors were achieved in tests with aqueous solutions alone. Nochar N960, a water sorbent, decreased hydrogen

  4. Affinity purification of DNA and RNA from environmental samples with peptide nucleic acid clamps.

    PubMed

    Chandler, D P; Stults, J R; Cebula, S; Schuck, B L; Weaver, D W; Anderson, K K; Egholm, M; Brockman, F J

    2000-08-01

    Bispeptide nucleic acids (bis-PNAs; PNA clamps), PNA oligomers, and DNA oligonucleotides were evaluated as affinity purification reagents for subfemtomolar 16S ribosomal DNA (rDNA) and rRNA targets in soil, sediment, and industrial air filter nucleic acid extracts. Under low-salt hybridization conditions (10 mM NaPO(4), 5 mM disodium EDTA, and 0.025% sodium dodecyl sulfate [SDS]) a PNA clamp recovered significantly more target DNA than either PNA or DNA oligomers. The efficacy of PNA clamps and oligomers was generally enhanced in the presence of excess nontarget DNA and in a low-salt extraction-hybridization buffer. Under high-salt conditions (200 mM NaPO(4), 100 mM disodium EDTA, and 0.5% SDS), however, capture efficiencies with the DNA oligomer were significantly greater than with the PNA clamp and PNA oligomer. Recovery and detection efficiencies for target DNA concentrations of > or =100 pg were generally >20% but depended upon the specific probe, solution background, and salt condition. The DNA probe had a lower absolute detection limit of 100 fg of target (830 zM [1 zM = 10(-21) M]) in high-salt buffer. In the absence of exogenous DNA (e.g., soil background), neither the bis-PNA nor the PNA oligomer achieved the same absolute detection limit even under a more favorable low-salt hybridization condition. In the presence of a soil background, however, both PNA probes provided more sensitive absolute purification and detection (830 zM) than the DNA oligomer. In varied environmental samples, the rank order for capture probe performance in high-salt buffer was DNA > PNA > clamp. Recovery of 16S rRNA from environmental samples mirrored quantitative results for DNA target recovery, with the DNA oligomer generating more positive results than either the bis-PNA or PNA oligomer, but PNA probes provided a greater incidence of detection from environmental samples that also contained a higher concentration of nontarget DNA and RNA. Significant interactions between probe

  5. Gap Junction Communication and the Propagation of Bystander Effects Induced by Microbeam Irradiation in Human Fibroblast Cultures: The Impact of Radiation Quality

    PubMed Central

    Autsavapromporn, Narongchai; Suzuki, Masao; Funayama, Tomoo; Usami, Noriko; Plante, Ianik; Yokota, Yuichiro; Mutou, Yasuko; Ikeda, Hiroko; Kobayashi, Katsumi; Kobayashi, Yasuhiko; Uchihori, Yukio; Hei, Tom K.; Azzam, Edouard I.; Murakami, Takeshi

    2014-01-01

    Understanding the mechanisms underlying the bystander effects of low doses/low fluences of low- or high-linear energy transfer (LET) radiation is relevant to radiotherapy and radiation protection. Here, we investigated the role of gap-junction intercellular communication (GJIC) in the propagation of stressful effects in confluent normal human fibroblast cultures wherein only 0.036–0.144% of cells in the population were traversed by primary radiation tracks. Confluent cells were exposed to graded doses from monochromatic 5.35 keV X ray (LET ~6 keV/μm), 18.3 MeV/u carbon ion (LET ~103 keV/μm), 13 MeV/u neon ion (LET ~380 keV/μm) or 11.5 MeV/u argon ion (LET ~1,260 keV/μm) microbeams in the presence or absence of 18-α-glycyrrhetinic acid (AGA), an inhibitor of GJIC. After 4 h incubation at 37°C, the cells were subcultured and assayed for micronucleus (MN) formation. Micronuclei were induced in a greater fraction of cells than expected based on the fraction of cells targeted by primary radiation, and the effect occurred in a dose-dependent manner with any of the radiation sources. Interestingly, MN formation for the heavy-ion microbeam irradiation in the absence of AGA was higher than in its presence at high mean absorbed doses. In contrast, there were no significant differences in cell cultures exposed to X-ray microbeam irradiation in presence or absence of AGA. This showed that the inhibition of GJIC depressed the enhancement of MN formation in bystander cells from cultures exposed to high-LET radiation but not low-LET radiation. Bystander cells recipient of growth medium harvested from 5.35 keV X-irradiated cultures experienced stress manifested in the form of excess micronucleus formation. Together, the results support the involvement of both junctional communication and secreted factor(s) in the propagation of radiation-induced stress to bystander cells. They highlight the important role of radiation quality and dose in the observed effects. PMID:23987132

  6. Modulation of human cell responses to space radiation by gap-junction communication

    NASA Astrophysics Data System (ADS)

    Autsavapromporn, Narongchai; de Toledo, Sonia M.; Buonanno, Manuela; Yang, Zhi; Harris, Andrew; Jay-Gerin, Jean-Paul; Azzam, Edouard

    Understanding the biological effects of space radiation and their underlying mechanism is critical to estimating the health risk associated with human exploration of space. A coordinated interaction of multiple cellular processes is likely involved in the sensing and processing of stressful effects induced by different types of space radiation. Here, we focused on the role of gap-junction intercellular communication (GJIC) in responses of human cells exposed to 1 GeV/n protons or 56 Fe-ions. We compared the results with data obtained in human cells exposed, in parallel, to γ-rays or α-particles. As expected, a higher level of cell killing and DNA damage, per unit dose, was induced in confluent, density-inhibited cells (98% in G0 /G1 ) exposed to α-particles or energetic 56 Fe-ions than γ-rays or protons. Strikingly, greatly attenuated effects occurred when sub-confluent cultures, synchronized in G0 /G1 ,were exposed to 56 Fe-ions. These data suggest that direct intercellular communication is involved in the effects of high linear energy transfer (LET) 56 Fe-ions. To examine the role of gap-junctions in propagating stressful effect, confluent cultures were exposed to 56 Fe-ions or α-particles and incubated for various time periods at 37° C in the presence or absence of the gap-junction inhibitor α-glycyrrhetinic acid (AGA). No repair of potentially lethal radiation damage occurred in cells incubated in the absence of AGA. In contrast, inhibition of functional GJIC significantly enhanced clonogenic survival of irradiated cells. To test the role of junctional channel permeability in the observed effects, we used human adenocarcinoma (HeLa) cells in which specific connexins (Cx) can be expressed in the absence of endogenous connexins. Whereas HeLa cells with selective inducible expression of Cx26 gap-junctions promoted radiation toxic effects, expression of Cx32 junctional channels in HeLa cells promoted pro-survival effects. Experiments are in progress to

  7. The Importance of Connexin Hemichannels During Chondroprogenitor Cell Differentiation in Hydrogel Versus Microtissue Culture Models

    PubMed Central

    Schrobback, Karsten; Klein, Travis Jacob

    2015-01-01

    Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell–cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell–cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5′-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular

  8. Anti-Inflammatory Effects of Levalbuterol-Induced 11β-Hydroxysteroid Dehydrogenase Type 1 Activity in Airway Epithelial Cells

    PubMed Central

    Randall, Matthew J.; Kostin, Shannon F.; Burgess, Edward J.; Hoyt, Laura R.; Ather, Jennifer L.; Lundblad, Lennart K.; Poynter, Matthew E.

    2015-01-01

    Airway epithelial NF-κB activation is observed in asthmatic subjects and is a cause of airway inflammation in mouse models of allergic asthma. Combination therapy with inhaled short-acting β2-agonists and corticosteroids significantly improves lung function and reduces inflammation in asthmatic subjects. Corticosteroids operate through a number of mechanisms to potently inhibit NF-κB activity. Since β2-agonists can induce expression of 11β-HSD1, which converts inactive 11-keto corticosteroids into active 11-hydroxy corticosteroids, thereby potentiating the effects of endogenous glucocorticoids, we examined whether this mechanism is involved in the inhibition of NF-κB activation induced by the β-agonist albuterol in airway epithelial cells. Treatment of transformed murine Club cells (MTCC) with (R)-albuterol (levalbuterol), but not with (S)- or a mixture of (R + S)- (racemic) albuterol, augmented mRNA expression of 11β-HSD1. MTCC were stably transfected with luciferase (luc) reporter constructs under transcriptional regulation by NF-κB (NF-κB/luc) or glucocorticoid response element (GRE/luc) consensus motifs. Stimulation of NF-κB/luc MTCC with lipopolysaccharide (LPS) or tumor necrosis factor-α (TNFα) induced luc activity, which was inhibited by pretreatment with (R)-, but not (S)- or racemic albuterol. Furthermore, pretreatment of GRE/luc MTCC with (R)-, but not with (S)- or racemic albuterol, augmented 11-keto corticosteroid (cortisone) induced luc activity, which was diminished by the 11β-HSD inhibitor glycyrrhetinic acid (18β-GA), indicating that there was a conversion of inactive 11-keto to active 11-hydroxy corticosteroids. LPS- and TNFα-induced NF-κB/luc activity was diminished in MTCC cells treated with a combination of cortisone and (R)-albuterol, an effect that was inhibited by 18β-GA. Finally, pretreatment of MTCC cells with the combination of cortisone and (R)-albuterol diminished LPS- and TNFα-induced pro-inflammatory cytokine

  9. Pharmacokinetic Profiles of Active Ingredients and Its Metabolites Derived from Rikkunshito, a Ghrelin Enhancer, in Healthy Japanese Volunteers: A Cross-Over, Randomized Study

    PubMed Central

    Kitagawa, Hiroyuki; Munekage, Masaya; Matsumoto, Takashi; Sadakane, Chiharu; Fukutake, Miwako; Aoki, Katsuyuki; Watanabe, Junko; Maemura, Kazuya; Hattori, Tomohisa; Kase, Yosio; Uezono, Yasuhito; Inui, Akio; Hanazaki, Kazuhiro

    2015-01-01

    Background Rikkunshito, a traditional Japanese (Kampo) medicine, has been used to treat upper gastrointestinal disorders such as functional dyspepsia and gastroesophageal reflux. This study investigated the exposure and pharmacokinetics of the ingredients of rikkunshito in healthy volunteers. Methods and Results First, an exploratory nonrandomized, open-label, one-period, noncrossover study using four healthy Japanese volunteers to detect 32 typical ingredients of rikkunshito in plasma and urine. As a result, 18 or 21 of 32 ingredients was detected in plasma or urine samples after oral administration of rikkunshito (7.5 g/day). Furthermore, a randomized, open-label, three-arm, three-period, crossover study using 21 subjects was conducted to determine the amounts of exposure and pharmacokinetic parameters of nine ingredients derived from rikkunshito (atractylodin, atractylodin carboxylic acid, pachymic acid, 3,3′,4′,5,6,7,8-heptamethoxyflavone, naringenin, nobiletin, liquiritigenin, isoliquiritigenin, and 18β-glycyrrhetinic acid) after oral administration of rikkunshito at three different doses (2.5, 5.0, or 7.5 g/day) during each period. The pharmacokinetic profiles of the nine ingredients in plasma were characterized. The geometric means (95% confidence interval) for the Cmax of the ingredients at a dose of 7.5 g were 1570 (1210–2040), 14,300 (12,200–16,800), 91.0 (71.8–115), 105 (75.6–144), 1150 (802–1650), 35.9 (24.6–52.5), 800 (672–952), 42.8 (30.4–60.3), and 55,600 (39,600–78,100) pg/mL, respectively, and for the AUC0–last were 1760 (1290–2390), 12700 (11,100–14,600), 1210 (882–1650), 225 (157–322), 4630 (2930–7320), 35.7 (20.4–62.7), 4040 (3260–5010), 122 (88.2–168), and 832,000 (628,000–1,100,000) pg·h/mL respectively. Conclusions We identified the ingredients of rikkunshito that are absorbed in humans. Furthermore, we determined the pharmacokinetics of nine ingredients derived from rikkunshito. This information

  10. Smooth muscle membrane potential modulates endothelium-dependent relaxation of rat basilar artery via myo-endothelial gap junctions.

    PubMed

    Allen, Tracy; Iftinca, Mircea; Cole, William C; Plane, Frances

    2002-12-15

    The release of endothelium-derived relaxing factors, such as nitric oxide (NO), is dependent on an increase in intracellular calcium levels ([Ca(2+)](i)) within endothelial cells. Endothelial cell membrane potential plays a critical role in the regulation of [Ca(2+)](i) in that calcium influx from the extracellular space is dependent on membrane hyperpolarization. In this study, the effect of inhibition of vascular smooth muscle delayed rectifier K(+) (K(DR)) channels by 4-aminopyridine (4-AP) on endothelium-dependent relaxation of rat basilar artery to acetylcholine (ACh) was assessed. ACh-evoked endothelium-dependent relaxations were inhibited by N-(Omega)-nitro-L-arginine (L-NNA) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), confirming a role for NO and guanylyl cyclase. 4-AP (300 microM) also suppressed ACh-induced relaxation, with the maximal response reduced from approximately 92 to approximately 33 % (n = 11; P < 0.01). However, relaxations in response to exogenous NO, applied in the form of authentic NO, sodium nitroprusside or diethylamineNONOate (DEANONOate), were not affected by 4-AP treatment (n = 3-11). These data are not consistent with the view that 4-AP-sensitive K(DR) channels are mediators of vascular hyperpolarization and relaxation in response to endothelium-derived NO. Inhibition of ACh-evoked relaxation by 4-AP was reversed by pinacidil (0.5-1 microM; n = 5) or 18beta-glycyrrhetinic acid (18betaGA; 5 microM; n = 5), indicating that depolarization and electrical coupling of the smooth muscle to the endothelium were involved. 4-AP caused depolarization of both endothelial and vascular smooth muscle cells of isolated segments of basilar artery (mean change 11 +/- 1 and 9 +/- 2 mV, respectively; n = 15). Significantly, 18betaGA almost completely prevented the depolarization of endothelial cells (n = 6), but not smooth muscle cells (n = 6) by 4-AP. ACh-induced hyperpolarization of endothelium and smooth muscle cells was also reduced by 4-AP

  11. A LC-ESI-MS method for the simultaneous determination of madecassoside and its metabolite madecassic acid in rat plasma: comparison pharmacokinetics in normal and collagen-induced arthritic rats.

    PubMed

    Wang, Ting; Leng, Dan-Dan; Gao, Fei-Fei; Jiang, Chun-Jie; Xia, Yu-Feng; Dai, Yue

    2014-12-01

    To develop a simple and highly sensitive high performance liquid chromatography with electrospray ionization mass spectrometric (LC-ESI-MS) method for the simultaneous determination of madecassoside and its major metabolite madecassic acid in rat plasma, and compare the pharmacokinetics of the two compounds in normal and collagen-induced arthritis (CIA) rats. Glycyrrhetinic acid was used as the internal standard (IS). Chromatographic separation was accomplished on an Inertsil ODS-3 column, using a gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1% (V/V) formic acid. Detection was achieved by ESI-MS under the negative selected ion monitoring (SIM) mode. In normal and CIA rats, madecassoside (30 mg·kg(-1)) was orally administered for 21 consecutive days from the day of arthritis onset. For madecassoside, the linear range was 10-1 000 ng·mL(-1) with the square regression coefficient (r) of 0.998 9, while for madecassic acid, the linear range was 10-500 ng·mL(-1) with the square regression coefficient (r) of 0.996 1. The lower limit of quantification was 10 ng·mL(-1) for both analytes. The intra- and inter-day precision ranged from 1.78% to 13.42% for madecassoside and 2.30% to 14.90% for madecassic acid, and the accuracy was between -0.95% and 6.30% for madecassoside and between -1.48% and 5.34% for madecassic acid. The average recoveries of madecassoside, madecassic acid and IS from spiked plasma samples were > 81%. The developed method was successfully applied to the pharmacokinetic study of madecassoside and madecassic acid in rats after an oral administration of madecassoside. During initial 7 days of dosing, the cmax and AUC of madecassoside were greatly decreased and Vd/F was markedly increased in CIA rats, and no significant difference was observed on the first day of dosing. In contrast, the T1/2, cmax and AUC of madecassic acid were significantly increased, and Ke of madecassic acid was greatly decreased in CIA

  12. Hematopoiesis: Gap Junction Intercellular Communication is Likely to be Involved in Regulation of Stroma-dependent Proliferation of Hemopoietic Stem Cells.

    PubMed

    Ploemacher, ROB E.; Mayen, ANGELIQUE E. M.; De Koning, ALEXANDRA E.; Krenacs, TIBOR; Rosendaal, MARTIN

    2000-01-01

    The 80-100 fold increased immunohistological expression of the Gap Junction (GJ) protein Connexin-43 in murine bone marrow during the neonatal period and directly following cytoreductive treatment of adult mice suggests that the regulation of stem cell proliferation may involve GJ Intercellular Communication (GJIC). Using a series of stromal cell lines from foetal liver and neonatal bone marrow we observed that the percentage of cells with GJIC, as indicated by dye-coupling using microinjection of lucifer yellow, correlated with the stromal support for late appearing clones formed by primitive stem cells (CAFC week 3-5). In order to functionally block all GJIC between mutual stromal cells and stromal cells and hemopoietic cells, in long-term stroma-supported flask (LTC) and CAFC cultures, the lipophilic compounds amphotericin-B (AB), nystatin, alpha-glycyrrhetinic acid, tetraphenylboron, dipicrylamine and arachidonic acid were tested for their effect on GJIC and CAFC support. Only AB and nystatin, which induced complete and prolonged GJIC blockade, were able to dramatically inhibit cobblestone area (CA) formation and CFU-C generation in LTC. This inhibition could be fully abrogated by withdrawing AB within the first 2 weeks of culture. Low AB concentrations stimulated CA formation. The AB-mediated inhibition of hemopoiesis probably involved direct stromal contact with stem cells because a) AB did not inhibit CFU-C generation when stem cells were cultured in trans-well inserts above the stroma; b) conditioned media from AB-containing or normal LTC did not inhibit colony formation by normal cells in semi-solid, non-stromal cultures, and c) AB did not inhibit colony formation by bone marrow cells in semi-solid culture nor did it inhibit growth or maintenance of stromal cells. In addition, The inhibition of hemopoiesis by AB could also not be explained by changes in the amount of cytokine and chemokine transcripts, including TGF-b1, in AB-blocked stromal cells. Our

  13. Uptake of locally applied deoxyglucose, glucose and lactate by axons and Schwann cells of rat vagus nerve

    PubMed Central

    Véga, Céline; Martiel, Jean-Louis; Drouhault, Delphine; Burckhart, Marie-France; Coles, Jonathan A

    2003-01-01

    We asked whether, in a steady state, neurons and glial cells both take up glucose sufficient for their energy requirements, or whether glial cells take up a disproportionate amount and transfer metabolic substrate to neurons. A desheathed rat vagus nerve was held crossways in a laminar flow perfusion chamber and stimulated at 2 Hz. 14C-labelled substrate was applied from a micropipette for 5 min over a < 0.6 mm band of the surface of the nerve. After 10-55 min incubation, the nerve was lyophilized and the longitudinal distribution of radioactivity measured. When the weakly metabolizable analogue of glucose, 2-deoxy-[U-14C]d-glucose (*DG), was applied, the profiles of the radioactivity broadened with time, reaching distances several times the mean length of the Schwann cells (0.32 mm; most of the Schwann cells are non-myelinating). The profiles were well fitted by curves calculated for diffusion in a single compartment, the mean diffusion coefficient being 463 ± 34 μm2 s−1 (± s.e.m., n = 16). Applications of *DG were repeated in the presence of the gap junction blocker, carbenoxolone (100 μm). The profiles were now narrower and better fitted with two compartments. One compartment had a coefficient not significantly different from that in the absence of the gap junction blocker (axons), the other compartment had a coefficient of 204 ± 24 μm2 s−1, n = 4. Addition of the gap junction blocker 18-α-glycyrrhetinic acid, or blocking electrical activity with TTX, also reduced longitudinal diffusion. Ascribing the compartment in which diffusion was reduced by these treatments to non-myelinating Schwann cells, we conclude that 78.0 ± 3.6 % (n = 9) of the uptake of *DG was into Schwann cells. This suggests that there was transfer of metabolic substrate from Schwann cells to axons. Local application of [14C]glucose or [14C]lactate led to variable labelling along the length of the nerve, but with both substrates narrow peaks were often present at the application site

  14. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model

    PubMed Central

    Sovadinova, Iva; Babica, Pavel; Böke, Hatice; Kumar, Esha; Wilke, Andrew; Park, Joon-Suk; Trosko, James E.; Upham, Brad L.

    2015-01-01

    Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. In conclusion: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap

  15. [Validation study of analysis of Malachite green in broiled eels (Kabayaki) by LC-MS/MS].

    PubMed

    Yamashita, Takeshi; Nishikawa, Kiyofumi; Shinozaki, Fumiyoshi; Banno, Yukinori; Kawakami, Masahiro

    2015-01-01

    An improved method for analysis of Malachite green (MG) and its metabolite, Leucomalachite green (LMG), in broiled eels without using dichloromethane was developed. This method was evaluated by means of recovery tests according to the guideline for validation of analytical methods by the Ministry of Health, Labour and Welfare of Japan. MG and LMG were extracted from spiked samples with acetonitrile and citric acid/disodium hydrogen phosphate buffer solution, and were salted-out with sodium chloride. The acetonitrile layer was dried over anhydrous sodium sulfate and purified on C18 and strongly acidic cation exchange columns. MG and LMG in the purified solution were determined quantitatively using LC-MS/MS by the internal standard method with surrogates, MG and LMG labeled with deuterium (MG-d5, LMG-d6). The recovery rates of MG and LMG were 99.2% and 93.6%, respectively. The relative standard deviations of repeatability were 2.2% for MG and 4.4% for LMG, and the relative standard deviations of within-laboratory reproducibility were 3.5% for MG and 5.1% for LMG.

  16. Involvement of prostaglandins and histamine in radiation-induced temperature responses in rats

    SciTech Connect

    Kandasamy, S.B.; Hunt, W.A. )

    1990-01-01

    Exposure of rats to 1-15 Gy of gamma radiation induced hyperthermia, whereas exposure to 20-150 Gy produced hypothermia. Since radiation exposure induced the release of prostaglandins (PGs) and histamine, the role of PGs and histamine in radiation-induced temperature changes was examined. Radiation-induced hyper- and hypothermia were antagonized by pretreatment with indomethacin, a cyclooxygenase inhibitor. Intracerebroventricular administration of PGE2 and PGD2 induced hyper- and hypothermia, respectively. Administration of SC-19220, a specific PGE2 antagonist, attenuated PGE2- and radiation-induced hyperthermia, but it did not antagonize PGD2- or radiation-induced hypothermia. Consistent with an apparent role of histamine in hypothermia, administration of disodium cromoglycate (a mast cell stabilizer), mepyramine (H1-receptor antagonist), or cimetidine (H2-receptor antagonist) attenuated PGD2- and radiation-induced hypothermia. These results suggest that radiation-induced hyperthermia is mediated via PGE2 and that radiation-induced hypothermia is mediated by another PG, possibly PGD2, via histamine.

  17. Photophysical properties of porphyrin photosensitizers

    NASA Astrophysics Data System (ADS)

    Dadeko, A. V.; Murav'eva, T. D.; Starodubtsev, A. M.; Gorelov, S. I.; Dobrun, M. V.; Kris'ko, T. K.; Bagrov, I. V.; Belousova, I. M.; Ponomarev, G. V.

    2015-10-01

    The photodynamic properties of a new photosensitizer—dimegin (disodium salt of 2,4-di(1- methoxyethyl)-deuteroporphyrin-IX)—are studied in comparison with the properties of photosensitizers used in medical practice, namely, Photoditazine (dimethylglucamine salt of chlorin e6) and Radachlorin (trisodium salt of chlorin e6). The spectral characteristics, singlet oxygen generation ability, luminescence efficiency, and photostability of these photosensitizers are studied upon irradiation by light-emitting diode arrays in different spectral ranges. The ability of photosensitizers to generate singlet oxygen was estimated with the use of tryptophan as a chemical trap. The photostability was estimated by a change in the optical density of solutions in the Soret band after irradiation. It is shown that the photodynamic properties are related to the specific features of the optical absorption spectrum of the material. The results of this work testify to the possibility of using the Dimegin photosensitizer as an efficient drug for photodynamic therapy and fluorescent diagnostics. Comparative studies of luminescence, singlet oxygen generation, and photostability have shown that Dimegin surpasses Photoditazine and Radachlorin in many characteristics. In the future, these studies will help to choose the most efficient irradiation sources for photodynamic therapy and fluorescent diagnostic.

  18. ATP-stabilized amorphous calcium carbonate nanospheres and their application in protein adsorption.

    PubMed

    Qi, Chao; Zhu, Ying-Jie; Lu, Bing-Qiang; Zhao, Xin-Yu; Zhao, Jing; Chen, Feng; Wu, Jin

    2014-05-28

    Calcium carbonate is a common substance found in rocks worldwide, and is the main biomineral formed in shells of marine organisms and snails, pearls and eggshells. Amorphous calcium carbonate (ACC) is the least stable polymorph of calcium carbonate, which is so unstable under normal conditions that it is difficult to be prepared in vitro because it rapidly crystallizes to form one of the more stable polymorphs in aqueous solution. Herein, we report the successful synthesis of highly stable ACC nanospheres in vitro using adenosine 5'-triphosphate disodium salt (ATP) as a stabilizer. The effect of ATP on the stability of ACC nanospheres is investigated. Our experiments show that ATP plays an unique role in the stabilization of ACC nanospheres in aqueous solution. Moreover, the as-prepared ACC nanospheres are highly stable in phosphate buffered saline for a relatively long period of time (12 days) even under relatively high concentrations of calcium and phosphate ions. The cytotoxicity tests show that the as-prepared highly stable ACC nanospheres have excellent biocompatibility. The highly stable ACC nanospheres have high protein adsorption capacity, implying that they are promising for applications in biomedical fields such as drug delivery and protein adsorption.

  19. Cromolyn as surface active drug (surfadrug): Effect of the self-association on diffusion and percutaneous permeation.

    PubMed

    Tavano, Lorena; Nicoletta, Fiore Pasquale; Picci, Nevio; Muzzalupo, Rita

    2016-03-01

    Cromolyn sodium, or disodium cromoglycate (CS), is a surface active drug: a pharmacologically active compound with an amphiphilic nature. At certain conditions it is able to self-associate in several kind of supramolecular aggregates. Since CS could play the role of both carrier and drug, bypassing the use of additional excipients and increasing the system biocompatibility, the effects of cromolyn self-aggregates on diffusion and percutaneous permeation across rabbit ear skin were investigated. Niosomes (vesicular systems, 0.5wt% of CS), monomeric and isotropic solutions (0.5 and 5wt% of CS), nematic (15wt% of CS) and hexagonal phases (30wt% of CS) were selected as supramolecular systems and tested as transdermal delivery systems. Results demonstrated that CS was able to form vesicular structures of about 500nm of diameter and this formulation gave the higher percutaneous permeation profile (systemic action), while isotropic solution and liquid crystals mesophases acted as slower release reservoir of drug on the skin surface (local action), as confirmed by diffusion coefficients. Diffusion rates through a synthetic membrane were dependent both on CS concentration present into the formulations and on its structural organization: maximum diffusion was noticed with isotropic solution, a lower amount of diffused cromolyn sodium was achieved by hexagonal phase. Consequently, CS appears as a versatile surfadrug as, depending on the disease degree, it is possible to modulate its permeation profile by choosing the most appropriate formulation.

  20. Redox cycling and generation of reactive oxygen species in commercial infant formulas.

    PubMed

    Boatright, William L; Crum, Andrea D

    2016-04-01

    Three nationally prominent commercial powdered infant formulas generated hydrogen peroxide, ranging from 10.46 to 11.62 μM, when prepared according to the manufacturer's instructions. Treating infant formulas with the chelating agent diethylene triamine pentaacetic acid (DTPA) significantly reduced H2O2 generation. In contrast, the addition of disodium ethylenediaminetetraacetic acid (EDTA) elevated the level of H2O2 generated in the same infant formulas by approximately 3- to 4-fold above the untreated infant formulas. The infant formulas contained ascorbate radicals ranging from about 138 nM to 40 nM. Treatment with catalase reduced the ascorbate radical contents by as much as 67%. Treatment with DTPA further reduced ascorbate radical signals to below quantifiable levels in most samples, further implicating the involvement of transition metal redox cycling in reactive oxygen species (ROS) formation. Supportive evidence of the generation of ROS is provided using luminol-enhanced luminescence (LEL) in both model mixtures of ascorbic acid and in commercial infant formulas. PMID:26593482

  1. Arsenic toxicity and HSP70 expression in Xenopus laevis embryos.

    PubMed

    Gornati, Rosalba; Monetti, Claudio; Vigetti, Davide; Bosisio, Stefano; Fortaner, Salvador; Sabbioni, Enrico; Bernardini, Giovanni; Prati, Mariangela

    2002-01-01

    The evaluation of the effect of trace metals on health can be difficult, because of their presence in the environment in various chemical forms. Exposure to arsenic compounds is an example of this complexity, as it can be present in the environment in inorganic and organic forms. The effects of arsenic in vertebrates are complicated by several variables, such as speciation of the element, the exposure route, and the susceptibility of the particular animal species. The embryotoxicity and teratogenicity of three arsenic species - sodium arsenite (NaAsO(2)), disodium hydrogen arsenate (Na(2)HAsO(4)) and dimethylarsinic acid [(CH3)2AsOOH] - were evaluated by the modified frog embryo teratogenic assay on Xenopus (FETAX). We also show how the classical FETAX endpoints, based on morphological and morphometrical analysis, can conveniently be integrated with the study of molecular markers. Possible changes in the expression of the mRNA for the heat-shock protein HSP70, following exposure to NaAsO(2), were examined by using the reverse transcriptase polymerase chain reaction. HSP70 mRNA is strongly induced by arsenic.

  2. Suppressive effects of co-stimulatory molecule expressions on mouse splenocytes by anti-allergic agents in vitro.

    PubMed Central

    Ito, J; Asano, K; Tryka, E; Kanai, K; Yamamoto, S; Hisamitsu, T; Suzaki, H

    2000-01-01

    The influence of anti-allergic drugs, epinastine hydrochloride (EP) and disodium cromoglycate (DSCG), on the co-stimulatory molecule expression was examined using in vitro cell culture technique. Spleen cells obtained from BALB/c mice 10 days after immunization with haemocyanin absorbed to aluminium hydroxide were cultured in the presence of 100.0 microg/ml haemocyanin and various concentrations of the agents. Low concentrations (<1.5 x 10(-4)M) of EP and DSCG did not influence spleen cell blastic activity induced by antigenic stimulation, whereas these agents caused significant inhibition of spleen cell activation when 2 x 10(-4) M of the agents were added to cell cultures. EP and DSCG also did not affect blastic activity of sensitized splenic T cells by anti-CD3 monoclonal antibody stimulation even when these cells were cultured in the presence of 2 x 10(-4) M of the agents. We next examined the influence of EP and DSCG on the expression of co-stimulatory molecules on spleen cells in response to antigenic stimulation. Sensitized spleen cells were cultured in the presence of 2 x 10(-4)M of the agents and the expression of molecules were examined by flow cytometer 24h later. EP and DSCG suppressed the expression of costimulatory molecules, CD40 and CD80, but not CD86, on splenic B cells which were enhanced by antigenic stimulation in vitro. PMID:10958379

  3. The release of spasmogenic substances from human chopped lung tissue and its inhibition

    PubMed Central

    Piper, Priscilla J.; Walker, Joyce L.

    1973-01-01

    1. Human lung tissue, passively sensitized with reaginic antibodies, released prostaglandins E1, E2 and F2α in addition to histamine and slow reacting substance (SRS-A), when exposed to the appropriate antigen. No rabbit aorta contracting substance (RCS) was detected. 2. Experiments with rats and guinea-pigs showed that the release of RCS is not confined to anaphylactic reactions mediated by non-reaginic antibodies but may be a feature of anaphylaxis in guinea-pigs alone. 3. Human lung tissue gently agitated with a blunt nylon rod liberated an E-type prostaglandin and RCS in addition to histamine and SRS-A. 4. Human isolated bronchial muscle was contracted by RCS. 5. Disodium cromoglycate antagonized the release of prostaglandins during anaphylaxis but not during agitation of human lung tissue, whereas indomethacin blocked the release of prostaglandins during agitation and anaphylaxis. 6. The release of an E-type prostaglandin during anaphylaxis in human lung tissue, which inhibits the further release of histamine could be another example of the regulatory role of prostaglandins in body functions. PMID:4352867

  4. Effects of phosphates on microstructure and bioactivity of micro-arc oxidized calcium phosphate coatings on Mg-Zn-Zr magnesium alloy.

    PubMed

    Pan, Y K; Chen, C Z; Wang, D G; Zhao, T G

    2013-09-01

    Calcium phosphate (CaP) coatings were prepared on Mg-Zn-Zr magnesium alloy by micro-arc oxidation (MAO) in electrolyte containing calcium acetate monohydrate (CH3COO)2Ca·H2O) and different phosphates (i.e. disodium hydrogen phosphate dodecahydrate (Na2HPO4·12H2O), sodium phosphate (Na3PO4·H2O) and sodium hexametaphosphate((NaPO3)6)). Scanning electron microscope (SEM), energy-dispersive X-ray spectrometry (EDS) and X-ray diffractometer (XRD) were employed to characterize the microstructure, elemental distribution and phase composition of the CaP coatings. Simulated body fluid (SBF) immersion test was used to evaluate the coating bioactivity and degradability. Systemic toxicity test was used to evaluate the coating biocompatibility. Fluoride ion selective electrode (ISE) was used to measure F(-) ions concentration during 30 days SBF immersion. The CaP coatings effectively reduced the corrosion rate and the surfaces of CaP coatings were covered by a new layer formed of numerous needle-like and scale-like apatites. The formation of these calcium phosphate apatites indicates that the coatings have excellent bioactivity. The coatings formed in (NaPO3)6-containging electrolyte exhibit thicker thickness, higher adhesive strength, slower degradation rate, better apatite-inducing ability and biocompatibility.

  5. Antibacterial and Antibiofilm Effects of Boron on Different Bacteria.

    PubMed

    Sayin, Zafer; Ucan, Uckun Sait; Sakmanoglu, Asli

    2016-09-01

    Boron (B) compounds are used in many fields ranging from medicine to industry. In this study, boric acid (BA) and disodium octaborate tetrahydrate (DOT) were evaluated for their antibacterial effects and antibiofilm capacities on selected strains of clinical and type cultures that are of veterinary concern (Staphylococcus aureus ATCC 25923, Aeromonas hydrophila ATCC 19570, Pseudomonas aeruginosa ATCC 27853, Brucella melitensis Rev1 and field isolates of Vibrio anguillarum, Aeromonas hydrophila, Yersinia ruckeri, Pseudomonas aeruginosa, Lactococcus garvieae, and Brucella abortus). Also, the inhibition of biofilm was monitored by scanning electron microscopy. The lowest MIC values of BA and DOT were measured, by broth method using microdilution, from Pseudomonas aeruginosa ATCC 27853, and were 0.385 and 0.644 mg/ml, respectively. Staphylococcus aureus was the most resistant to both BA and DOT. Using the microplate method, we observed that the strongest positivities for biofilm production were presented by Pseudomonas aeruginosa ATCC 27853 and also a clinical isolate of Lactococcus garviea. Lower values in the MIC scores for both B compounds were tested by measuring the inhibitory effect on biofilm production. We found that all the bacterial strains inhibited biofilm formation with the exception of the Pseudomonas aeruginosa strains for BA only and an isolate of Lactococcus garviea for DOT only. Such effects by BA and DOT are worth discussing in order to find novel approaches for different functions in medicine and industry using the bacteria tested. PMID:26864941

  6. Improved nonreductive O-glycan release by hydrazinolysis with ethylenediaminetetraacetic acid addition.

    PubMed

    Kozak, Radoslaw P; Royle, Louise; Gardner, Richard A; Bondt, Albert; Fernandes, Daryl L; Wuhrer, Manfred

    2014-05-15

    The study of protein O-glycosylation is receiving increasing attention in biological, medical, and biopharmaceutical research. Improved techniques are required to allow reproducible and quantitative analysis of O-glycans. An established approach for O-glycan analysis relies on their chemical release in high yield by hydrazinolysis, followed by fluorescent labeling at the reducing terminus and high-performance liquid chromatography (HPLC) profiling. However, an unwanted degradation known as "peeling" often compromises hydrazinolysis for O-glycan analysis. Here we addressed this problem using low-molarity solutions of ethylenediaminetetraacetic acid (EDTA) in hydrazine for O-glycan release. O-linked glycans from a range of different glycoproteins were analyzed, including bovine fetuin, bovine submaxillary gland mucin, and serum immunoglobulin A (IgA). The data for the O-glycans released by hydrazine with anhydrous EDTA or disodium salt dihydrate EDTA show high yields of the native O-glycans compared with the peeled product, resulting in a markedly increased robustness of the O-glycan profiling method. The presented method for O-glycan release demonstrates significant reduction in peeling and reduces the number of sample handling steps prior to release.

  7. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2004-12-01

    Gateways to Clinical Trials is a guide to the most recent clinical trials in current literature and congresses. The data in the following tables has been retrieved from the Clinical Studies Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issue focuses on the following selection of drugs: Abetimus sodium, ademetionine, agalsidase alfa, agalsidase beta, alemtuzumab, alfimeprase, AMG-162, androgel, anidulafungin, antigastrin therapeutic vaccine, aripiprazole, atomoxetine hydrochloride; Bazedoxifene acetate, bevacizumab, bosentan; Caldaret hydrate, canfosfamide hydrochloride, choriogonadotropin alfa, ciclesonide, combretastatin A-4 phosphate, CY-2301; Darbepoetin alfa, darifenacin hydrobromide, decitabine, degarelix acetate, duloxetine hydrochloride; ED-71, enclomiphene citrate, eplerenone, epratuzumab, escitalopram oxalate, eszopiclone, ezetimibe; Fingolimod hydrochloride, FP-1096; HMR-3339A, HSV-TK/GCV gene therapy, human insulin, HuOKT3gamma1(Ala234-Ala235); Idursulfase, imatinib mesylate, indiplon, InnoVax C insulin glargine, insulin glulisine, irofulven; Labetuzumab, lacosamide, lanthanum carbonate, LyphoDerm, Lyprinol; Magnesium sulfate, metelimumab, methylphenidate hydrochloride; Natalizumab, NO-aspirin; OROS(R); PC-515, pegaptanib sodium, peginterferon alfa-2a, peginterferon alfa-2b, peginterferon alfa-2b/ribavirin, pemetrexed disodium, peptide YY3-36, posaconazole, pregabalin, PT-141, pyridoxamine; R-744, ramelteon, ranelic acid distrontium salt, rebimastat, repinotan hydrochloride, rhC1, rhGAD65, rosiglitazone maleate/metformin hydrochloride; Sardomozide, solifenacin succinate; Tadalafil, taxus, telavancin, telithromycin, tenofovir disoproxil fumarate, teriparatide, testosterone transdermal patch, tetomilast, tirapazamine, torcetrapib; Valspodar, vardenafil hydrochloride hydrate, vildagliptin; Yttrium Y90 epratuzumab; Ziprasidone hydrochloride.

  8. A comparative evaluation of the effect of various additives on selected physical properties of white mineral trioxide aggregate

    PubMed Central

    Prasad, Anushree; Pushpa, Shankarappa; Arunagiri, Doraiswamy; Sawhny, Asheesh; Misra, Abhinav; Sujatha, Ramamurthy

    2015-01-01

    Aims: This study examined the setting time, compressive strength, and pH of white mineral trioxide aggregate (MTA) mixed with various additives: Calcium chloride (CaCl2), calcium formate (CaF), disodium hydrogen orthophosphate (Na2HPO4). Materials and Methods: Group 1 (Control) was obtained by mixing MTA with distilled water. In Groups 2 and 3, MTA containing 10% CaCl2 and 20% CaF, respectively, was mixed with distilled water. In Group 4, MTA was mixed with 15% Na2HPO4. Setting time, compressive strength, and pH of each group were examined. Statistical Analysis Used: Analysis was done using Statistical Package for Social Sciences (SPSS) version 14. A P-value < 0.05 was considered statistically significant. Comparison of mean values was done using analysis of variance (ANOVA) with post-hoc Games-Howell test. Results: The setting time of test groups were significantly shorter than that of control group (P < 0.001). The compressive strengths of test groups were lower than that of control group (P < 0.001). The pH value obtained for Groups 3 and 4 were higher than that of the control group (P < 0.001). Conclusions: Study result showed that additives significantly reduced the setting time of MTA and also maintained the pH at a high value. However, there was not much improvement in the compressive strength of the material. PMID:26069412

  9. Optimization and characterization of biosurfactant production from marine Vibrio sp. strain 3B-2

    PubMed Central

    Hu, Xiaoke; Wang, Caixia; Wang, Peng

    2015-01-01

    A biosurfactant-producing bacterium, designated 3B-2, was isolated from marine sediment and identified as Vibrio sp. by 16S rRNA gene sequencing. The culture medium composition was optimized to increase the capability of 3B-2 for producing biosurfactant. The produced biosurfactant was characterized in terms of protein concentration, surface tension, and oil-displacement efficiency. The optimal medium for biosurfactant production contained: 0.5% lactose, 1.1% yeast extract, 2% sodium chloride, and 0.1% disodium hydrogen phosphate. Under optimal conditions (28°C), the surface tension of crude biosurfactant could be reduced to 41 from 71.5 mN/m (water), while its protein concentration was increased to up to 6.5 g/L and the oil displacement efficiency was improved dramatically at 6.5 cm. Two glycoprotein fractions with the molecular masses of 22 and 40 kDa were purified from the biosurfactant, which held great potential for applications in microbial enhanced oil recovery and bioremediation. PMID:26441908

  10. Effect of applied voltage on surface properties of anodised titanium in mixture of β-glycerophosphate (β-GP) and calcium acetate (CA)

    NASA Astrophysics Data System (ADS)

    Chuan, Lee Te; Rathi, Muhammad Fareez Mohamad; Abidin, Muhamad Yusuf Zainal; Abdullah, Hasan Zuhudi; Idris, Maizlinda Izwana

    2015-07-01

    Anodic oxidation is a surface modification method which combines electric field driven metal and oxygen ion diffusion for formation of oxide layer on the anode surface. This method has been widely used to modify the surface morphology of biomaterial especially titanium. This study aimed to investigate the effect of applied voltage on titanium. Specifically, the titanium foil was anodised in mixture of β-glycerophosphate disodium salt pentahydrate (β-GP) and calcium acetate monohydrate (CA) with different applied voltage (50-350 V), electrolyte concentration (0.04 M β-GP + 0.4 M CA), anodising time (10minutes) and current density (50 and 70 mA.cm-2) at room temperature. Surface oxide properties of anodised titanium were characterised by digital single-lens reflex camera (DSLR camera), field emission scanning electron microscope (FESEM) and atomic force microscopy (AFM). At lower applied voltage (≤150 V), surface of titanium foils were relatively smooth. With increasing applied voltage (≥250 V), the oxide layer became more porous and donut-shaped pores were formed on the surface of titanium foils. The AFM results indicated that the surface roughness of anodised titanium increases with increasing of applied voltage. The porous and rough surface is able to promote the osseointegration and reduce the suffering time of patient.

  11. Inhibition of irritation and contact hypersensitivity by phenoxyacetic acid methyl ester in mice.

    PubMed

    Wille, J J; Kydonieus, A; Kalish, R S

    2000-01-01

    New anti-irritant treatments are required to prevent irritation and sensitization reactions to consumer medicines and dermatological drugs. We report here that phenoxyacetic acid methyl ester (PAME) is an effective agent to prevent and treat irritant and allergic contact dermatitis. Balb/c mice skin-treated with 1% PAME do not lose weight relative to vehicle-treated mice, nor is it irritating to mouse skin. Topical PAME prevents skin irritation to a wide variety of irritants including: arachidonic acid, capsaicin, sodium lauryl sulfate (SLS), disodium laureth sulfosuccinate and tetradecanoylphorbol-13-acetate. Histological studies showed that 1% PAME greatly diminished dermal neutrophilic infiltration and dermal capillary vessel dilation, and prevented epidermal hyperproliferation and hyperkeratosis that accompanies detergent (SLS)-induced skin irritation. Topical PAME inhibited ear swelling following ear challenge during the elicitation phase of contact hypersensitivity in mice sensitized with 1-chloro-2, 4-dinitrochlorobenzene (DNCB), oxazolone and the hair coloring dye rho-phenylenediamine (PPD). Finally, topical administration of 1% PAME prior to PPD or DNCB sensitization prevented the induction phase of contact hypersensitivity. These results indicate that PAME represents a potential new category of potent topical anti-inflammatory agents. PMID:10754454

  12. Cytocompatibility assessment of chemical surface treatments for phosphate glass to improve adhesion between glass and polyester.

    PubMed

    S Hasan, M; Ahmed, I; Parsons, A J; Walker, G S; Scotchford, C A

    2013-11-01

    Fully resorbable phosphate glass fiber reinforced polymer composites have shown real potential for replacing some of the existing metallic bone fracture fixation devices. However, some of these composites have not provided suitable mechanical strength profiles over the required healing period for bone. Typically, it has been seen that these composites can lose up to 50% or more of their strength within the first week of degradation. Functionalizing the glass surface to promote polymer adhesion or to introduce hydrophobicity at the glass surface could potentially introduce control over the mechanical properties of the composite and their retention. In this study eight chemical agents namely, Glycerol 2-phosphate disodium salt; 3-phosphonopropionic acid; 3-aminopropyltriethoxy silane; etidronic acid; hexamethylene diisocyanate; sorbitol/sodium ended PLA oligomers and amino phosphonic acid, were selected to functionalise the bulk phosphate glass surface. Selected chemical agents had one functional group (-OH or O C N) to react with the glass and another functionality (either -OH, NH2, or Na) to react with the polymer matrix and/or produce hydrophobicity at the fiber surface. Bulk phosphate glass surface-treated with the above agents were assessed for the cytotoxicity of degradation products cell-material interaction in short- and long-term direct cytocompatibility studies. Results obtained from these cytocompatibility studies (using human osteosarcoma (MG63) and primary human osteoblast cell lines) revealed no cytotoxicity from the degradation products and a response comparable to controls in terms of cell functions (attachment, viability, metabolic activity, proliferation, and differentiation) and morphology.

  13. In vitro and in vivo anti-allergic activity of soy sauce.

    PubMed

    Kobayashi, Makio; Matsushita, Hiroaki; Yoshida, Kazutoshi; Tsukiyama, Ryo-Ichi; Sugimura, Takashi; Yamamoto, Kenji

    2004-11-01

    Soy sauce (Shoyu) is a traditional fermented seasoning of Japan and available throughout the world. Polysaccharides were obtained from dialysate of Shoyu, and these Shoyu polysaccharides (SPS) were examined for anti-allergic activity in vitro and in vivo. The SPS originated from partially-degraded polysaccharides of soybeans by mold enzymatic hydrolyses, and Shoyu contained about 1% (w/v) SPS. First, the inhibitory effects of SPS on hyaluronidase, which is known to be related to inflammation and allergic responses, were as potent as those of an anti-allergic medicine, disodium cromoglycate. Second, SPS significantly inhibited the release of histamine from rat basophilic leukemia (RBL-2H3) cells, which had been induced by the antigen. Third, orally administered SPS had a significant suppressive effect on passive cutaneous anaphylaxis induced in the ears of mice. These results suggest that SPS may have anti-allergic activities, and soy sauce is a potentially promising seasoning for the treatment of allergic diseases through food.

  14. Effects of tea saponins on rumen microbiota, rumen fermentation, methane production and growth performance--a review.

    PubMed

    Wang, Jia-Kun; Ye, Jun-An; Liu, Jian-Xin

    2012-04-01

    Reducing methane emission from ruminant animals has implications not only for global environmental protection but also for efficient animal production. Tea saponins (TS) extracted from seeds, leaves or roots of tea plant are pentacyclic triterpenes. They have a lasting antiprotozoal effect, but little effect on the methanogen population in sheep. There was no significant correlation between the protozoa counts and methanogens. The TS decreased methanogen activity. It seems that TS influenced the activity of the methanogens indirectly via the depressed ciliate protozoal population. The TS addition decreased fungal population in the medium containing rumen liquor in in vitro fermentation, but no such effect was observed in the rumen liquor of sheep fed TS. Tea saponins had a minor effect on the pattern of rumen fermentation and hence on nutrient digestion. When added at 3 g/day in diets, TS could improve daily weight gain and feed efficiency in goats. No positive associative effect existed between TS and disodium fumarate or soybean oil on methane suppression. Inclusion of TS in diets may be an effective way for improving feed efficiency in ruminants.

  15. 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. PMID:24191443

  16. Body burdens of lead in hypertensive nephropathy

    SciTech Connect

    Osterloh, J.D.; Selby, J.V.; Bernard, B.P.; Becker, C.E.; Menke, D.J.; Tepper, E.; Ordonez, J.D.; Behrens, B. )

    1989-09-01

    Chronic lead exposure resulting in blood lead concentrations that exceed 1.93 mumol/l (40 micrograms/dl) or chelatable urinary lead excretion greater than 3.14 mumol (650 micrograms) per 72 h has been associated with renal disease. A previous study had found greater chelatable urine lead excretion in subjects with hypertension and renal failure than in controls with renal failure due to other causes, although mean blood lead concentrations averaged 0.92 mumol/l (19 micrograms/dl). To determine if chelatable urinary lead, blood lead, or the hematologic effect of lead (zinc protoporphyrin) were greater in hypertensive nephropathy (when hypertension precedes elevation of serum creatinine) than in other forms of mild renal failure, we compared 40 study subjects with hypertensive nephropathy to 24 controls having a similar degree of renal dysfunction due to causes other than hypertension. Lead burdens were similar in both the study and control groups as assessed by 72-h chelatable urinary lead excretion after intramuscular injection of calcium disodium EDTA (0.74 +/- 0.63 vs. 0.61 +/- 0.40 mumol per 72 h, respectively), and by blood lead (0.35 +/- 0.23 vs. 0.35 +/- 0.20 mumol/l). We conclude that subjects from a general population with hypertensive nephropathy do not have greater body burdens of lead than renal failure controls.

  17. A novel blue luminescent material Na2[Co(C2O4)2(H2O)2]·6H2O: synthesis, structure, luminescence and magnetic properties.

    PubMed

    Saritha, A; Raju, B; Narsimhulu, M; Rao, D Narayana; Raghavaiah, P; Hussain, K A

    2016-05-17

    The synthesis, crystal structure and physical properties of new disodium trans-diaquabis(oxalato)cobaltate(ii)hexahydrate {Na2[Co(C2O4)2(H2O)2]·6H2O} crystals have been investigated. Single crystal X-ray analysis reveals that this compound crystallizes in the triclinic system with the space group P1[combining macron]. The structure of this complex consists of [Co(C2O4)2(H2O)2](2-) anionic units with a slightly distorted octahedral geometry of cobalt surrounded by four oxygen atoms of two oxalate groups. The anionic units are interlinked by two Na(+) ions with different octahedral and distorted octahedral environments. The electronic absorption spectra of the compound exhibit bands at 208, 246 and 526 nm in the UV and visible regions. A strong blue luminescence was observed at room temperature when excited at 355 nm. The M(H) curve at 2 K shows a significant nonlinear behaviour with almost zero coercivity which clearly indicates an extremely weak antiferromagnetic/ferromagnetic state of the complex.

  18. The Examination of Afyonkarahisar's Geothermal System Corrosion

    NASA Astrophysics Data System (ADS)

    Buyuksagis, A.; Erol, S.

    2013-02-01

    Corrosion and scaling of metal surfaces are the major problems caused by geothermal fluids when metallic structures are used. This article describes a study of corrosion and scaling problems in the Afyonkarahisar Geothermal Heating System (AFJET) in Afyonkarahisar, Turkey. Water analysis, XRD, SEM, EDX, IC, ICP-OES analyses, and electrochemical methods were used in this study. Pentasodium triphosphate (Na5P3O10), maleic anhydride (C4H2O3), and 1,3-benzendisulfonic acid disodium salt (C6H4Na2O6S2) were used as corrosion inhibitors. Tests were carried out using geothermal water from AF11 well. The experimental temperatures were chosen as 298, 333, and 358 K. Inhibitor concentrations were chosen as 1 × 10-1, 1 × 10-2, 1 × 10-3, and 1 × 10-4 mol/dm3. Moreover, mixed inhibitor solutions were prepared using the inhibitor concentrations that showed the best inhibition. The first mixed inhibitor solution showed 96% inhibition. The second mixed inhibitor solution showed 90% inhibition. The tested inhibitors act as anodic inhibitors. XRD analysis shows that there is CaCO3 aragonite scaling in the system. Increasing TDS, alkalinity, and hardness all promote scale formation. The photomicrographs from SEM-EDX and the metallographic microscope show that the tested inhibitors form a protective film on the surface. IC and ICP-OES analyses show that the concentration of Ca2+ is very high, which supports scale formation.

  19. Redox cycling and generation of reactive oxygen species in commercial infant formulas.

    PubMed

    Boatright, William L; Crum, Andrea D

    2016-04-01

    Three nationally prominent commercial powdered infant formulas generated hydrogen peroxide, ranging from 10.46 to 11.62 μM, when prepared according to the manufacturer's instructions. Treating infant formulas with the chelating agent diethylene triamine pentaacetic acid (DTPA) significantly reduced H2O2 generation. In contrast, the addition of disodium ethylenediaminetetraacetic acid (EDTA) elevated the level of H2O2 generated in the same infant formulas by approximately 3- to 4-fold above the untreated infant formulas. The infant formulas contained ascorbate radicals ranging from about 138 nM to 40 nM. Treatment with catalase reduced the ascorbate radical contents by as much as 67%. Treatment with DTPA further reduced ascorbate radical signals to below quantifiable levels in most samples, further implicating the involvement of transition metal redox cycling in reactive oxygen species (ROS) formation. Supportive evidence of the generation of ROS is provided using luminol-enhanced luminescence (LEL) in both model mixtures of ascorbic acid and in commercial infant formulas.

  20. Self-Assembly of Gemini Surfactants

    NASA Astrophysics Data System (ADS)

    Yethiraj, Arun; Mondal, Jagannath; Mahanthappa, Mahesh

    2013-03-01

    The self-assembly behavior of Gemini (dimeric or twin-tail) dicarboxylate disodium surfactants is studied using molecular dynamics simulations. This gemini architecture, in which two single tailed surfactants are joined through a flexible hydrophobic linker, has been shown to exhibit concentration-dependent aqueous self-assembly into lyotropic phases including hexagonal, gyroid, and lamellar morphologies. Our simulations reproduce the experimentally observed phases at similar amphiphile concentrations in water, including the unusual ability of these surfactants to form gyroid phases over unprecedentedly large amphiphile concentration windows. We demonstrate quanitative agreement between the predicted and experimentally observed domain spacings of these nanostructured materials. Through careful conformation analyses of the surfactant molecules, we show that the gyroid phase is electrostatically stabilized related to the lamellar phase. By starting with a lamellar phase, we show that decreasing the charge on the surfactant headgroups by carboxylate protonation or use of a bulkier tetramethyl ammonium counterion in place of sodium drives the formation of a gyroid phase.