Science.gov

Sample records for disodium succinoyl glycyrrhetinate

  1. Final report on the safety assessment of Glycyrrhetinic Acid, Potassium Glycyrrhetinate, Disodium Succinoyl Glycyrrhetinate, Glyceryl Glycyrrhetinate, Glycyrrhetinyl Stearate, Stearyl Glycyrrhetinate, Glycyrrhizic Acid, Ammonium Glycyrrhizate, Dipotassium Glycyrrhizate, Disodium Glycyrrhizate, Trisodium Glycyrrhizate, Methyl Glycyrrhizate, and Potassium Glycyrrhizinate.

    PubMed

    2007-01-01

    11beta -hydroxysteroid dehydrogenase-2 (11beta -OHSD2) in the kidney. Glycyrrhetinic Acid and its derivatives block gap junction intracellular communication in a dose-dependent manner in animal and human cells, including epithelial cells, fibroblasts, osteoblasts, hepatocytes, and astrocytes; at high concentrations, it is cytotoxic. Glycyrrhetinic Acid and Glycyrrhizic Acid protect liver tissue from carbon tetrachloride. Glycyrrhizic Acid has been used to treat chronic hepatitis, inhibiting the penetration of the hepatitis A virus into hepatocytes. Glycyrrhetinic Acid and Glycyrrhizic Acid have anti-inflammatory effects in rats and mice. The acute intraperitoneal LD(50) for Glycyrrhetinic Acid in mice was 308 mg/kg and the oral LD(50) was > 610 mg/kg. The oral LD(50) in rats was reported to be 610 mg/kg. Higher LD(50) values were generally reported for salts. Little short-term, subchronic, or chronic toxicity was seen in rats given ammonium, dipotassium, or disodium salts of Glycyrrhizic Acid. Glycyrrhetinic Acid was not irritating to shaved rabbit skin, but was considered slightly irritating in an in vitro test. Glycyrrhetinic Acid inhibited the mutagenic activity of benzo[a]pyrene and inhibited tumor initiation and promotion by other agents in mice. Glycyrrhizic Acid inhibited tumor initiation by another agent, but did not prevent tumor promotion in mice. Glycyrrhizic Acid delayed mortality in mice injected with Erlich ascites tumor cells, but did not reduce the mortality rate. Ammonium Glycyrrhizate was not genotoxic in in vivo and in vitro cytogenetics assays, the dominant lethal assay, an Ames assay, and heritable translocation tests, except for possible increase in dominant lethal mutations in rats given 2000 mg/kg day(-1) in their diet. Disodium Glycyrrhizate was not carcinogenic in mice in a drinking water study at exposure levels up to 12.2 mg/kg day(-1) for 96 weeks. Glycyrrhizate salts produced no reproductive or developmental toxicity in rats, mice

  2. Antibacterial Effects of Glycyrrhetinic Acid and Its Derivatives on Staphylococcus aureus

    PubMed Central

    Oyama, Kentaro; Kawada-Matsuo, Miki; Oogai, Yuichi; Hayashi, Tetsuya; Nakamura, Norifumi; Komatsuzawa, Hitoshi

    2016-01-01

    Staphylococcus aureus is a major pathogen in humans and causes serious problems due to antibiotic resistance. We investigated the antimicrobial effect of glycyrrhetinic acid (GRA) and its derivatives against 50 clinical S. aureus strains, including 18 methicillin-resistant strains. The minimum inhibitory concentrations (MICs) of GRA, dipotassium glycyrrhizate, disodium succinoyl glycyrrhetinate (GR-SU), stearyl glycyrrhetinate and glycyrrhetinyl stearate were evaluated against various S. aureus strains. Additionally, we investigated the bactericidal effects of GRA and GR-SU against two specific S. aureus strains. DNA microarray analysis was also performed to clarify the mechanism underlying the antibacterial activity of GR-SU. We detected the antimicrobial activities of five agents against S. aureus strains. GRA and GR-SU showed strong antibacterial activities compared to the other three agents tested. At a higher concentration (above 2x MIC), GRA and GR-SU showed bactericidal activity, whereas at a concentration of 1x MIC, they showed a bacteriostatic effect. Additionally, GRA and GR-SU exhibited a synergistic effect with gentamicin. The expression of a large number of genes (including transporters) and metabolic factors (carbohydrates and amino acids) was altered by the addition of GR-SU, suggesting that the inhibition of these metabolic processes may influence the degree of the requirement for carbohydrates or amino acids. In fact, the requirement for carbohydrates or amino acids was increased in the presence of either GRA or GR-SU. GRA and GR-SU exhibited strong antibacterial activity against several S. aureus strains, including MRSA. This activity may be partly due to the inhibition of several pathways involved in carbohydrate and amino acid metabolism. PMID:27820854

  3. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... containing dried bananas 2 315 Promote color retention. Salad dressing 75 Preservative. Sandwich spread 100... banana component of cereal product. (2) With calcium disodium EDTA (calcium disodium ethylenediamine...

  4. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... products containing dried bananas 2 315 Promote color retention. Salad dressing 75 Preservative. Sandwich... dried banana component of cereal product. (2) With calcium disodium EDTA (calcium disodium...

  5. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... products containing dried bananas 2 315 Promote color retention. Salad dressing 75 Preservative. Sandwich... dried banana component of cereal product. (2) With calcium disodium EDTA (calcium disodium...

  6. 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... dried banana component of cereal product. (2) With calcium disodium EDTA (calcium disodium...

  7. 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... dried banana component of cereal product. (2) With calcium disodium EDTA (calcium disodium...

  8. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace- tate... food additive contains a minimum of 99 percent disodium ethylenediaminetetraacetate dihydrate...

  9. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace- tate... food additive contains a minimum of 99 percent disodium ethylenediaminetetraacetate dihydrate...

  10. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace- tate... food additive contains a minimum of 99 percent disodium ethylenediaminetetraacetate dihydrate...

  11. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive Listing § 573.360 Disodium EDTA. The food additive disodium EDTA (disodium ethylenediaminetetraace- tate... food additive contains a minimum of 99 percent disodium ethylenediaminetetraacetate dihydrate...

  12. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 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 generally...

  13. 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 generally...

  14. 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 generally...

  15. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 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 generally...

  16. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Disodium phosphate. 182.6290 Section 182.6290 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) SUBSTANCES GENERALLY RECOGNIZED AS SAFE Sequestrants 1 § 182.6290 Disodium phosphate. (a) Product. Disodium phosphate...

  17. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 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 generally...

  18. 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 as...

  19. 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 as...

  20. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 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 as...

  1. 21 CFR 182.6290 - Disodium phosphate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 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 as...

  2. 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

  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

    2015-11-17

    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.

  4. Molecular Aggregation in Disodium Cromoglycate

    NASA Astrophysics Data System (ADS)

    Singh, Gautam; Agra-Kooijman, D.; Collings, P. J.; Kumar, Satyendra

    2012-02-01

    Details of molecular aggregation in the mesophases of the anti-asthmatic drug disodium cromoglycate (DSCG) have been studied using x-ray synchrotron scattering. The results show two reflections, one at wide angles corresponding to π-π stacking (3.32 å) of molecules, and the other at small angles which is perpendicular to the direction of molecular stacking and corresponds to the distance between the molecular aggregates. The latter varies from 35 - 41 å in the nematic (N) phase and 27 -- 32 å in the columnar (M) phase. The temperature evolution of the stack height, positional order correlations in the lateral direction, and orientation order parameter were determined in the N, M, and biphasic regions. The structure of the N and M phases and the nature of the molecular aggregation, together with their dependence on temperature and concentration, will be presented.

  5. 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. ...

  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 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-). (b...

  8. 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-). (b...

  9. 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-). (b...

  10. 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.

  11. Lysine, disodium guanylate and disodium inosinate as flavor enhancers in low-sodium fermented sausages.

    PubMed

    Campagnol, Paulo Cezar Bastianello; dos Santos, Bibiana Alves; Terra, Nelcindo Nascimento; Pollonio, Marise Aparecida Rodrigues

    2012-07-01

    Fermented sausages were produced with 50% replacement of NaCl with KCl and with addition of lysine, disodium guanylate, and disodium inosinate. The sausage production was monitored with physical, chemical and microbiological analyses. The final products were submitted to a consumer study. The replacement of NaCl with KCl did not cause changes in the technological process. However, defects in the sensory quality were detected. Lysine at a concentration of 1% with disodium inosinate (300 mg/kg) and disodium guanylate (300 mg/kg) reduced the sensory defects caused by the replacement of 50% NaCl with KCl allowing the preparation of sensory acceptable fermented sausages with a 50% decrease in sodium.

  12. 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

  13. 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, FEEDS, AND RELATED PRODUCTS FOOD ADDITIVES PERMITTED IN FEED AND DRINKING WATER OF ANIMALS Food Additive...

  14. Aspen flakeboard treated with disodium octaborate tetrahydrate

    Treesearch

    Robert H. White; John Forsman; John R. Erickson

    2008-01-01

    In this project, we investigated mechanical properties and fire performance of aspen flakeboards manufactured with the fire-retardant chemical disodium octaborate tetrahydrate (DOT). Flakeboards were prepared using two levels of adhesive loading (5% and 7% methylene diphenyl diisocyanate (MDI)) and three levels of fire-retardant treatments (6%, 9%, and 12%). DOT is a...

  15. 21 CFR 172.530 - Disodium guanylate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Disodium guanylate. 172.530 Section 172.530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD..., at a level not in excess of that reasonably required to produce the intended effect....

  16. Metabolism of glycyrrhetic acid by rat liver microsomes: glycyrrhetinate dehydrogenase.

    PubMed

    Akao, T; Akao, T; Kobashi, K

    1990-02-06

    Glycyrrhetic acid, derived from a main component of liquorice, was converted to 3-ketoglycyrrhetic acid reversibly by rat liver homogenates in the presence of NADPH or NADP+. Glycyrrhetic acid-oxidizing and 3-ketoglycyrrhetic acid-reducing activities were localized in microsomes among the subcellular fractions of rat liver. Glycyrrhetic acid-oxidizing activity and 3-ketoglycyrrhetic acid-reducing activities showed pH optima at 6.3 and 8.5, respectively, and required NADP+ or NAD+ and NADPH or NADH, respectively, indicating that these activities were due to glycyrrhetinate dehydrogenase. The dehydrogenase was not solubilized from the membranes by the treatment with 1 M NaCl or sonication, indicating that the enzyme is a membrane component. The dehydrogenase was solubilized with detergents such as Emalgen 913, Triton X-100 and sodium cholate, and then separated from 3 beta-hydroxysteroid dehydrogenase (5 beta-androstan-3 beta-ol-17-one-oxidizing activity) by butyl-Toyopearl 650 M column chromatography. Partially purified enzyme catalyzed the reversible reaction between glycyrrhetic acid and 3-ketoglycyrrhetic acid, but was inactive toward 3-epiglycyrrhetic acid and other steroids having the 3 beta-hydroxyl group. The enzyme required NADP+ and NADPH for the highest activities of oxidation and reduction, respectively, and NAD+ and NADH for considerable activities, similar to the results with microsomes. From these results the enzyme is defined as glycyrrhetinate dehydrogenase, being quite different from 3 beta-hydroxysteroid dehydrogenase of Ruminococcus sp. from human intestine, which is active for both glycyrrhetic acid and steroids having the 3 beta-hydroxyl group.

  17. Discovery of glycyrrhetinic acid as an orally active, direct inhibitor of blood coagulation factor xa.

    PubMed

    Jiang, Lilong; Wang, Qiong; Shen, Shu; Xiao, Tongshu; Li, Youbin

    2014-03-01

    Factor Xa (FXa) plays an important role in blood coagulation. This study investigated glycyrrhetinic acid, a small molecule derived from Chinese herbs, and whether it has a direct inhibitory effect on FXa to display its anticoagulant activity. Enzyme activities of FXa, plasmin, trypsin and thrombin, inhibition of FXa enzyme kinetics and plasma clotting time by glycyrrhentinic acid were performed in vitro. A rat tail-bleeding model and a rat venous stasis model were also used to evaluate in vivo tail-bleeding time and thrombus formation, respectively. Glycyrrhetinic acid in vitro directly inhibited FXa uncompetitivly with IC50 of 32.6 ± 1.24 μmol/L, and displayed 2-, 14- and 20-fold selectivity for FXa when compared to plasmin, thrombin and trypsin, respectively. The plasma clotting time was increased in a dose-dependent manner. The prothrombin time doubled (PT2), when the concentration of glycyrrhetinic acid reached 2.02 mmol/L. During in vivo experiments intragastric administration of glycyrrhetinic acid caused a dose-dependent reduction in thrombus weight on the rat venous stasis model (all P<0.05). 50 mg/kg glycyrrhetinic acid resulted in 34.8% of venous thrombus weight lost, compared to the control. In addition, 200, 300 and 400 mg/kg doses of glycyrrhetinic acid caused a moderate hemorrhagic effect in the rat tail-bleeding model by prolonging bleeding time 1.1-, 1.5- and 1.9-fold compared to the control, respectively. Glycyrrhetinic acid is a direct inhibitor of FXa that is effective by oral administration, and with further research could be used to treat blood coagulation disorders. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Mechanism of the 6-Hydroxy-3-succinoyl-pyridine 3-Monooxygenase Flavoprotein from Pseudomonas putida S16*

    PubMed Central

    Yu, Hao; Hausinger, Robert P.; Tang, Hong-Zhi; Xu, Ping

    2014-01-01

    6-Hydroxy-3-succinoyl-pyridine (HSP) 3-monooxygenase (HspB), a flavoprotein essential to the pyrrolidine pathway of nicotine degradation, catalyzes pyridine-ring β-hydroxylation, resulting in carbon-carbon cleavage and production of 2,5-dihydroxypyridine. Here, we generated His6-tagged HspB in Escherichia coli, characterized the properties of the recombinant enzyme, and investigated its mechanism of catalysis. In contrast to conclusions reported previously, the second product of the HspB reaction was shown to be succinate, with isotope labeling experiments providing direct evidence that the newly introduced oxygen atom of succinate is derived from H2O. Phylogenetic analysis reveals that HspB is the most closely related to two p-nitrophenol 4-monooxygenases, and the experimental results exhibit that p-nitrophenol is a substrate of HspB. The reduction of HspB (with maxima at 375 and 460 nm, and a shoulder at 485 nm) by NADH was followed by stopped-flow spectroscopy, and the rate constant for reduction was shown to be stimulated by HSP. Reduced HspB reacts with oxygen to form a C(4a)-(hydro)peroxyflavin intermediate with an absorbance maximum at ∼400 nm within the first few milliseconds before converting to the oxidized flavoenzyme species. The formed C(4a)-hydroperoxyflavin intermediate reacts with HSP to form an intermediate that hydrolyzes to the products 2,5-dihydroxypyridine and succinate. The investigation on the catalytic mechanism of a flavoprotein pyridine-ring β-position hydroxylase provides useful information for the biosynthesis of pyridine derivatives. PMID:25172510

  19. Cyclic-RGDfK peptide conjugated succinoyl-TPGS nanomicelles for targeted delivery of docetaxel to integrin receptor over-expressing angiogenic tumours.

    PubMed

    Kulhari, Hitesh; Pooja, Deep; Shrivastava, Shweta; Telukutala, Srinivasa R; Barui, Ayan K; Patra, Chitta Ranjan; Naidu Vegi, Ganga Modi; Adams, David J; Sistla, Ramakrishna

    2015-08-01

    Docetaxel (DTX) is an anticancer drug that is used alone and in combination with other drugs to treat tumours. However, it suffers from the drawback of non-specific cytotoxicity. To improve the therapeutic potential of DTX, we report the synthesis of cRGDfK peptide-conjugated succinoyl-TPGS (tocopheryl polyethylene glycol succinate) nanomicelles for targeted delivery of DTX. Among RGD (Arg-Gly-Asp) peptides, cRGDfK peptide shows specificity towards αvβ3 integrin receptors that are most commonly over-expressed in tumour cells. To cRGDfK peptide, succinoylated TPGS was synthesised and conjugated to cRGDfK peptide using a carbodiimide reaction. Peptide-conjugated DTX loaded nanomicelles (PDNM) displayed small particle size with a narrow distribution, controlled drug release and high physicochemical stability. Cytotoxicity, cellular uptake, apoptosis and anti-angiogenic comparisons of unconjugated nanomicelles to PDNM in DU145 human prostate cancer cells and HUVECs (Human Umblical Vein Endothelial Cells) clearly revealed the importance of the cRGDfK peptide in enhancing the drug delivery performance of nanomicelles. Common to many chemotherapeutic agents for cancer, systemic toxicity remains a big concern. In this article, the authors attempted to address this issue by conjugating RGD based peptides to Docetaxel, which would target integrins expressed on tumor cell surface. The experimental data revealed enhanced drug delivery. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Glycyrrhetinic acid alleviates radiation-induced lung injury in mice

    PubMed Central

    Chen, Jinmei; Zhang, Weijian; Zhang, Lurong; Zhang, Jiemin; Chen, Xiuying; Yang, Meichun; Chen, Ting; Hong, Jinsheng

    2017-01-01

    Radiation-induced lung injury (RILI) is a common complication of thoracic radiotherapy, but efficacious therapy for RILI is lacking. This study ascertained whether glycyrrhetinic acid (GA; a functional hydrolyzed product of glycyrrhizic acid, which is extracted from herb licorice) can protect against RILI and investigated its relationship to the transforming growth factor (TGF)-β1/Smads signaling pathway. C57BL/6 mice were divided into four groups: a control group, a GA group and two irradiation (IR) groups. IR groups were exposed to a single fraction of X-rays (12 Gy) to the thorax and administered normal saline (IR + NS group) or GA (IR + GA group). Two days and 17 days after irradiation, histologic analyses were performed to assess the degree of lung injury, and the expression of TGF-β1, Smad2, Smad3 and Smad7 was recorded. GA administration mitigated the histologic changes of lung injury 2 days and 17 days after irradiation. Protein and mRNA expression of TGF-β1, Smad2 and Smad3, and the mRNA level of Smad7, in lung tissue were significantly elevated after irradiation. GA decreased expression of TGF-β1, Smad2 and Smad3 in lung tissue, but did not increase Smad7 expression. GA can protect against early-stage RILI. This protective effect may be associated with inhibition of the TGF-β1/Smads signaling pathway. PMID:27672101

  1. Glycyrrhetinic Acid Mediated Drug Delivery Carriers for Hepatocellular Carcinoma Therapy.

    PubMed

    Cai, Yuee; Xu, Yingqi; Chan, Hon Fai; Fang, Xiaobin; He, Chengwei; Chen, Meiwan

    2016-03-07

    Glycyrrhetinic acid (GA), the main hydrolysate of glycyrrhizic acid extracted from the root of licorice, has been used in hepatocellular carcinoma (HCC) therapy. Particularly, GA as a ligand in HCC therapy has been widely explored in different drug delivery systems, including liposomes, micelles, and nanoparticles. There is considerable interest worldwide with respect to the development of GA-modified drug delivery systems due to the extensive presence of GA receptors on the surface of hepatocyte. Up until now, much work has been focused on developing GA-modified drug delivery systems which bear good liver- or hepatocyte-targeted efficiency both in vitro and in vivo. Owing to its contribution in overcoming the limitations of low lipophilicity and poor bioavailability as well as its ability to promote receptor-mediated endocytosis, GA-modified drug delivery systems play an important role in enhancing liver-targeting efficacy and thus are focused on the treatment of HCC. Moreover, since GA-modified delivery systems present more favorable pharmacokinetic properties and hepatocyte-targeting effects, they may be a promising formulation for GA in the treatment of HCC. In this review, we will give an overview of GA-modified novel drug delivery systems, paying attention to their efficacy in treating HCC and discussing their mechanism and the treatment effects.

  2. Interaction of glycyrrhizin and glycyrrhetinic acid with DNA.

    PubMed

    Nafisi, Shohreh; Bonsaii, Mahyar; Manouchehri, Firouzeh; Abdi, Khosrou

    2012-01-01

    Glycyrrhizin (GL), a molecule of glycyrrhetinic acid (GA), is an aqueous extract from licorice root. These compounds are well known for their anti-inflammatory, hepatocarcinogenesis, antiviral, and interferon-inducing activities. This study is the first attempt to investigate the binding of GL and GA with DNA. The effect of ligand complexation on DNA aggregation and condensation was investigated in aqueous solution at physiological conditions, using constant DNA concentration (6.25 mM) and various ligands/polynucleotide (phosphate) ratios of 1/240, 1/120, 1/80, 1/40, 1/20, 1/10, 1/5, 1/2, and 1/1. Fourier transform infrared and ultraviolet (UV)-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of ligand-DNA complexes in aqueous solution. Spectroscopic evidence showed that GL and GA bind DNA via major and minor grooves as well as the backbone phosphate group with overall binding constants of K(GL-DNA)=5.7×10(3) M(-1), K(GA-DNA)=5.1×10(3) M(-1). The affinity of ligand-DNA binding is in the order of GL>GA. DNA remained in the B-family structure, whereas biopolymer aggregation occurred at high triterpenoid concentrations.

  3. 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. A novel multicompartimental system based on aminated poly(vinyl alcohol) microspheres/succinoylated pullulan microspheres for oral delivery of anionic drugs.

    PubMed

    Constantin, M; Fundueanu, G; Bortolotti, F; Cortesi, R; Ascenzi, P; Menegatti, E

    2007-02-07

    Poly(vinyl alcohol) (PVA) microspheres were prepared by dispersion reticulation with glutaraldehyde and further aminated. These microspheres were firstly loaded with diclofenac (DF) and then entrapped in cellulose acetate butyrate (CAB) microcapsules by an o/w solvent evaporation technique for intestinal delivery of drug. The encapsulated PVA microspheres due to their low swelling degree in intestinal fluids, do not have enough force to produce the disruption of CAB shell, therefore different amounts of succinoylated pullulan microspheres (SP-Ms) (exchange capacity up to 5.2 meq/g) were co-encapsulated. The SP-Ms do not swell in acidic pH, but swell up to 20-times in intestinal fluids causing the rupture of CAB shell and facilitating the escape of loaded PVA microspheres.

  5. Binding effect of fluorescence labeled glycyrrhetinic acid with GA receptors in hepatocellular carcinoma cells.

    PubMed

    Sun, Yu-Qi; Dai, Chun-Mei; Zheng, Yan; Shi, Shu-Dan; Hu, Hai-Yang; Chen, Da-Wei

    2017-11-01

    Glycyrrhetinic acid (GA) is a natural active component from licorice, which is broadly used in traditional Chinese medicine. Lots of glycyrrhetinic acid receptors (GA-R) are proved to locate on the surface of liver cells. Many reports about the hepatocellular carcinoma (HCC) treatment were dependent on GA modified carriers. However, the reality of GA-R in HCC cells was not clear. In this paper, 18β-glycyrrhetinic acid (18β-GA) was labeled with fluorescence (FITC) by chemical synthesis. Together with the binding effect of fluorescence labeled glycyrrhetinic acid (FITC-GA), the competitive action of 18β-GA with GA-R was investigated in HCC cells. The results showed that in HepG2 cells, 18β-GA and FITC-GA presented similar cytotoxicity. The specific binding saturation of GA showed the dissociation constant (Kd) was 7.457±2.122pmol/L and the maximum binding counts (Bmax) was 2.385±0.175pmol/2.5×10(6) cells, respectively. FITC-GA bound to cytomembrane specifically and 18β-GA competed to bind the sites significantly in HepG2 cells. Therefore, there is binding effect between fluorescence labeled GA and GA-R. The GA-R on HCC cells is confirmed as expected, which provides a useful reference of active target modified by GA and a novel approach for receptors and ligands study. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Modulation by glycyrrhetinic acid derivatives of TPA-induced mouse ear oedema.

    PubMed Central

    Inoue, H.; Mori, T.; Shibata, S.; Koshihara, Y.

    1989-01-01

    1. The anti-inflammatory effects of glycyrrhetinic acid and its derivatives on TPA (12-O-tetradecanoylphorbol-13-acetate)-induced mouse ear oedema were studied. The mechanisms of TPA-induced ear oedema were first investigated with respect to the chemical mediators. 2. The formation of ear oedema reached a maximum 5 h after TPA application (2 micrograms per ear) and the prostaglandin E2 (PGE2) production of mouse ear increased with the oedema formation. 3. TPA-induced ear oedema was prevented by actinomycin D and cycloheximide (0.1 mg per ear, respectively) when applied during 60 min after TPA treatment. 4. Of glycyrrhetinic acid derivatives examined, dihemiphthalate derivatives (IIe, IIe', IIIa, IIIa', IVa, IVa') most strongly inhibited ear oedema on both topical (ID50, 1.6 mg per ear for IIe, 2.0 mg per ear for IIIa and 1.6 mg per ear for IVa) and oral (ID50, 88 mg kg-1 for IIe', 130 mg kg-1 for IIIa' and 92 mg kg-1 for IVa') administration. 5. Glycyrrhetinic acid (Ia) and its derivatives applied 30 min before TPA treatment were much more effective in inhibiting oedema than when applied 30 min after TPA. A dihemiphthalate of triterpenoid compound IVa completely inhibited oedema, even when applied 3 h before TPA treatment. 6. Glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the parent compounds, produced little inhibition by oral administration at less than 200 mg kg-1. 7. These results suggest that the dihemiphthalate derivatives of triterpenes derived from glycyrrhetinic acid by chemical modification are useful for the treatment of skin inflammation by both topical and oral application. PMID:2924072

  7. Disodium cromoglycate inhibits production of immunoglobulin E.

    PubMed

    Seo, S B; Park, S J; Park, S T; Cho, C C; Park, B H; Lee, S J; Kim, H M; Kajiuchi, T; Shin, T Y

    2001-05-01

    Disodium cromoglycate (DSCG) has been shown to inhibit the release of mediators from mast cells. In the present study, the effect of DSCG on active anaphylactic reaction was studied in mice. DSCG dose-dependently inhibited the active systemic anaphylactic reaction and serum immunoglobulin (Ig)E production induced by immunization with ovalbumin, Bordetella pertussis toxin and aluminum hydroxide gel. DSCG strongly inhibited IL-4-dependent IgE production by lipopolysaccharide-stimulated murine whole spleen cells. In the case of U266 human IgE-bearing B cells, DSCG also showed an inhibitory effect on the IgE production. These results suggest that DSCG has an anti-anaphylactic activity by inhibition of IgE production from B cells.

  8. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... COLOR ADDITIVES EXEMPT FROM CERTIFICATION Cosmetics § 73.2120 Disodium EDTA-copper. (a) Identity. The... in the coloring of shampoos which are cosmetics. (d) Labeling requirements. The labeling of the color...

  9. Gallbladder opacification on gadoxetate disodium-enhanced CT scan.

    PubMed

    Karam, Adib R; Scortegagna, Eduardo; Chen, Byron Y; Dupuis, Carolyn S; Coughlin, Dennis D

    2017-04-01

    This study aimed to evaluate the radiologist's ability to identify excreted gadoxetate disodium within the gallbladder on CT scan. Thirty three healthy adults underwent imaging of the liver during work-up for potential liver donation. Three patients had undergone prior cholecystectomy and therefore were excluded. Imaging consisted of gadoxetate disodium-enhanced magnetic resonance cholangiography (MRC) and multiphase contrast-enhanced CT scan of the abdomen and pelvis. Two fellowship-trained abdominal imaging radiologists, who were blinded to the MRC images and the contrast agent used during MRC, independently reviewed the CT scans of the 30 patients that were included. The scans were evaluated for the presence or absence of abnormal hyperdensity within the gallbladder. Three patients did not receive intravenous gadoxetate disodium, 4 patients had their MRC after the CT scan, and 1 patient had the CT scans 5 days following the MRC. Twenty two patients had the CT scan within 24 h following the gadoxetate disodium-enhanced MRC. Of the 22 patients expected to have gadolinium in the gallbladder, both reviewers identified hyperdensity in the same 20 patients (90%). Both reviewers reported no abnormal hyperdensity within the gallbladder in the remaining 10 patients. CT scan can reveal excreted gadoxetate disodium within the gallbladder lumen and therefore gadoxetate disodium-enhanced CT scan can potentially play a role in the evaluation of cystic duct patency and work-up of acute cholecystitis.

  10. Synthesis and pro-apoptotic activity of novel glycyrrhetinic acid derivatives.

    PubMed

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

    2011-03-21

    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. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. 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

  12. Reaction of disodium cromoglycate with hydrated electrons

    SciTech Connect

    Carmichael, A.J.; Arroyo, C.M.; Cockerham, L.G.

    1988-01-01

    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 (O/sub 2//sup -/.) in intestinal and cerebral vascular disorders following ischemia and ionizing radiation, respectively. O/sub 2//sup -/. is formed during radiolysis in the reaction between hydrated electrons (e-aq) and dissolved oxygen. For this reason, the efficiency of DSCG to scavenge e-q and possibly prevent the formation of O/sub 2//sup -/. was studied. Hydrated electrons were produced by photolysis of potassium ferrocyanide solutions. The rate constant, k = 2.92 x 10(10) M-1s-1 for the reaction between e-aq and DSCG was determined in competition experiments using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). This spin trap reacts rapidly with e-aq followed by protonation to yield the ESR observable DMPO-H spin adduct. The results show that DSCG is an efficient e-aq scavenger and may effectively compete with oxygen for e-aq preventing the radiolytic formation of O/sub 2//sup -/..

  13. Crystal structure and characterization of pyrroloquinoline quinone disodium trihydrate

    PubMed Central

    2012-01-01

    Background Pyrroloquinoline quinone (PQQ), a tricarboxylic acid, has attracted attention as a growth factor, and its application to supplements and cosmetics is underway. The product used for these purposes is a water-soluble salt of PQQ disodium. Although in the past, PQQ disodiumpentahydrates with a high water concentration were used, currently, low hydration crystals of PQQ disodiumpentahydrates are preferred. Results We prepared a crystal of PQQ disodium trihydrate in a solution of ethanol and water, studied its structure, and analyzed its properties. In the prepared crystal, the sodium atom interacted with the oxygen atom of two carboxylic acids as well as two quinones of the PQQ disodium trihydrate. In addition, the hydration water of the prepared crystal was less than that of the conventional PQQ disodium crystal. From the results of this study, it was found that the color and the near-infrared (NIR) spectrum of the prepared crystal changed depending on the water content in the dried samples. Conclusions The water content in the dried samples was restored to that in the trihydrate crystal by placing the samples in a humid environment. In addition, the results of X-ray diffraction (XRD) and X-ray diffraction-differential calorimetry (XRD-DSC) analyses show that the phase of the trihydrate crystal changed when the crystallization water was eliminated. The dried crystal has two crystalline forms that are restored to the original trihydrate crystals in 20% relative humidity (RH). This crystalline (PQQ disodium trihydrate) is stable under normal environment. PMID:22713213

  14. Green strategy from waste to value-added-chemical production: efficient biosynthesis of 6-hydroxy-3-succinoyl-pyridine by an engineered biocatalyst

    PubMed Central

    Yu, Hao; Tang, Hongzhi; Xu, Ping

    2014-01-01

    Value-added intermediates produced by microorganisms during the catabolism of N-heterocycles are potential building blocks for agrochemical synthesis and pharmaceutical production. 6-Hydroxy-3-succinoyl-pyridine (HSP), an intermediate in nicotine degradation, is an important precursor for the synthesis of drugs and compounds with biological activities. In the present study, we show that an engineered biocatalyst, Pseudomonas putida P-HSP, efficiently produced HSP from the renewable raw material of tobacco-waste that contains a high concentration of nicotine. The genetically constructed strain P-HSP realized a high accumulation of HSP, and HSP production was 3.7-fold higher than the non-engineered strain S16. Under optimal conditions, HSP was produced at high concentrations of 6.8 g l−1 and 16.3 g l−1 from tobacco-waste and nicotine, respectively. This work demonstrates a green strategy to block the catabolic pathway of N-heterocycles, which is a promising approach for the mutasynthesis of valuable compounds. PMID:24953905

  15. The protection of glycyrrhetinic acid (GA) towards acetaminophen (APAP)-induced toxicity partially through fatty acids metabolic pathway.

    PubMed

    Yang, Hua; Jiang, Tingshu; Li, Ping; Mao, Qishan

    2015-09-01

    Acetaminophen (APAP)-induced liver toxicity remains the key factor limiting the clinical application of APAP, and herbs are the important sources for isolation of compounds preventing APAP-induced toxicity. To investigate the protection mechanism of glycyrrhetinic acid towards APAP-induced liver damage using metabolomics method. APAP-induced liver toxicity model was made through intraperitoneal injection (i.p.) of APAP (400 mg/kg). Glycyrrhetinic acid was dissolved in corn oil, and intraperitoneal injection (i.p.) of glycyrrhetinic acid (500 mg/kg body weight) was performed for 20 days before the injection of APAP. UPLC-ESI-QTOF MS was employed to analyze the metabolomic profile of serum samples. The pre-treatment of glycyrrhetinic acid significantly protected APAP-induced toxicity, indicated by the histology of liver, the activity of ALT and AST. Metabolomics showed that the level of palmtioylcarnitine and oleoylcarnitine significantly increased in serum of APAP-treated mice, and the pre-treatment with GA can prevent this elevation of these two fatty acid-carnitines. Reversing the metabolism pathway of fatty acid is an important mechanism for the protection of glycyrrhetinic acid towards acetaminophen-induced liver toxicity.

  16. Glycyrrhetinic acid exhibits strong inhibitory effects towards UDP-glucuronosyltransferase (UGT) 1A3 and 2B7.

    PubMed

    Huang, Yin-Peng; Cao, Yun-Feng; Fang, Zhong-Ze; Zhang, Yan-Yan; Hu, Cui-Min; Sun, Xiao-Yu; Yu, Zhen-Wen; Zhu, Xu; Hong, Mo; Yang, Lu; Sun, Hong-Zhi

    2013-09-01

    The aim of the present study is to evaluate the inhibitory effects of liver UDP-glucuronosyltransferases (UGTs) by glycyrrhizic acid and glycyrrhetinic acid, which are the bioactive ingredients isolated from licorice. The results showed that glycyrrhetinic acid exhibited stronger inhibition towards all the tested UGT isoforms, indicating that the deglycosylation process played an important role in the inhibitory potential towards UGT isoforms. Furthermore, the inhibition kinetic type and parameters were determined for the inhibition of glycyrrhetinic acid towards UGT1A3 and UGT2B7. Data fitting using Dixon and Lineweaver-Burk plots demonstrated that the inhibition of UGT1A3 and UGT2B7 by glycyrrhetinic acid was best fit to competitive and noncompetitive type, respectively. The second plot using the slopes from Lineweaver-Burk plots versus glycyrrhetinic acid concentrations was employed to calculate the inhibition kinetic parameters (K(i)), and the values were calculated to be 0.2 and 1.7 μM for UGT1A3 and UGT2B7, respectively. All these results remind us the possibility of UGT inhibition-based herb-drug interaction. However, the explanation of these in vitro parameters should be paid more caution due to complicated factors, including the probe substrate-dependent UGT inhibition behaviour, environmental factors affecting the abundance of herbs' ingredients, and individual difference of pharmacokinetic factors.

  17. 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...

  18. 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...

  19. 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 (P-91...

  20. 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 (P-91...

  1. 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 (P-91...

  2. 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. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. [The suppression of bronchospasm with disodium cromoglycate (DSCG) (author's transl)].

    PubMed

    Ferlitsch, A; Kummer, F; Haber, P

    1980-01-01

    The protective effect of DSCG (disodium cromoglycate) was tested in 23 patients with artificial bronchospasm induced by specific allergen. After premedication with DSCG there was no arise of airway resistance (Rt) in 11 of 23 patients. In 4 patients with significant bronchial reaction, spontaneous remission could be registrated. In 8 patients DSCG could not suppress artificial bronchospasm. The clinically relevant aspects of these findings are being discussed.

  4. Oral Calcium Disodium Versenate in Treatment of Lead Poisoning

    PubMed Central

    Williams, J. D.; Matthews, G. A.; Judd, A. W.

    1962-01-01

    A clinical trial of oral calcium disodium versenate (E.D.T.A.) in eight lead workers is described. A short course of versenate given while the men continued at work produced no side-effects. Complete overhaul of the processes and protective devices was made in the factory. Clinical, biochemical, and haematological improvement followed the removal of up to 250 mg. lead in each case. The mode of action and possible uses and abuses of oral versenate are discussed. PMID:14007184

  5. Selective inhibition of 11beta-hydroxysteroid dehydrogenase 1 by 18alpha-glycyrrhetinic acid but not 18beta-glycyrrhetinic acid.

    PubMed

    Classen-Houben, Dirk; Schuster, Daniela; Da Cunha, Thierry; Odermatt, Alex; Wolber, Gerhard; Jordis, Ulrich; Kueenburg, Bernhard

    2009-02-01

    Elevated cortisol concentrations have been associated with metabolic diseases such as diabetes type 2 and obesity. 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 1, catalyzing the conversion of inactive 11-ketoglucocorticoids into their active 11beta-hydroxy forms, plays an important role in the regulation of cortisol levels within specific tissues. The selective inhibition of 11beta-HSD1 is currently considered as promising therapeutic strategy for the treatment of metabolic diseases. In recent years, natural compound-derived drug design has gained considerable interest. 18beta-glycyrrhetinic acid (GA), a metabolite of the natural product glycyrrhizin, is not selective and inhibits both 11beta-HSD1 and 11beta-HSD2. Here, we compare the biological activity of 18beta-GA and its diastereomer 18alpha-GA against the two enzymes in lysates of transfected HEK-293 cells and show that 18alpha-GA selectively inhibits 11beta-HSD1 but not 11beta-HSD2. This is in contrast to 18beta-GA, which preferentially inhibits 11beta-HSD2. Using a pharmacophore model based on the crystal structure of the GA-derivative carbenoxolone in complex with human 11beta-HSD1, we provide an explanation for the differences in the activities of 18alpha-GA and 18beta-GA. This model will be used to design novel selective derivatives of GA.

  6. Antitumor Agents 255. Novel Glycyrrhetinic Acid-Dehydrozingerone Conjugates as Cytotoxic Agents

    PubMed Central

    Tatsuzaki, Jin; Taniguchi, Masahiko; Bastow, Kenneth F.; Nakagawa-Goto, Kyoko; Morris-Natschke, Susan L.; Itokawa, Hideji; Baba, Kimiye; Lee, Kuo-Hsiung

    2007-01-01

    Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anticancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap, 1A9, and KB cells with ED50 values of 0.6, 0.8, and 0.9 μM, respectively. Similar conjugates between DZ and OA or UA were inactive suggesting that the GA component is critical for activity. Notably, although GA-DZ conjugates showed potent cytotoxic activity, the individual components (GA and DZ analogs) were inactive. Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anticancer drug discovery and development. PMID:17591444

  7. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Betamethasone acetate and betamethasone disodium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.161 Betamethasone acetate and betamethasone disodium phosphate aqueous suspension. (a) Chemical names. Betamethasone acetate: 9-α-Fluoro-16-β-methylprednisolone - 21...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Betamethasone acetate and betamethasone disodium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.161 Betamethasone acetate and betamethasone disodium phosphate aqueous suspension. (a) Chemical names. Betamethasone acetate: 9-α-Fluoro-16-β-methylprednisolone - 21...

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Betamethasone acetate and betamethasone disodium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.161 Betamethasone acetate and betamethasone disodium phosphate aqueous suspension. (a) Chemical names. Betamethasone acetate: 9-α-Fluoro-16-β-methylprednisolone - 21...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Betamethasone acetate and betamethasone disodium... INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.161 Betamethasone acetate and betamethasone disodium phosphate aqueous suspension. (a) Chemical names. Betamethasone acetate: 9-α-Fluoro-16-β-methylprednisolone - 21...

  11. 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.

  12. Influence of disodium EDTA on the nucleation and growth of struvite and carbonate apatite

    NASA Astrophysics Data System (ADS)

    Prywer, Jolanta; Olszynski, Marcin

    2013-07-01

    The effect of disodium EDTA, as an additive, on the crystallization of struvite and carbonate apatite was studied. The growth of struvite crystals and carbonate apatite occurred in the solution of artificial urine at 37 °C and at the condition emulating real urinary tract infection. The results demonstrate that the addition of disodium EDTA increases the induction time and decreases the growth efficiency compared to the baseline (without disodium EDTA). The struvite crystal mean and median diameters were found to decrease in the presence of disodium EDTA but the crystal morphology and habit remain almost unchanged. Disodium EDTA has demonstrated its potential to be further investigated in the presence of bacteria and in vivo conditions.

  13. Disposition of disodium cromoglycate administered in three particle sizes.

    PubMed Central

    Curry, S H; Taylor, A J; Evans, S; Godfrey, S; Zeidifard, E

    1975-01-01

    1 Disodium cromoglycate (DSCG) was administered in three particle sizes to five human subjects. 2 Urinary excretion of DSCG, as a proportion of the dose, was highest following small particles; the lower values recorded following intermediate-sized and large particles were similar. 3 DSCG deposited in the mouth was highest following large particles; the lower values recorded following intermediate-sized and small particles were similar. 4 The data were examined in relation to the recent observation that the protective effect of small particles of DSCG is dramatically superior to that of large particles. PMID:825134

  14. Systemic mastocytosis: control of lifelong diarrhea by ingested disodium cromoglycate

    PubMed Central

    Dolovich, J.; Punthakee, N. D.; MacMillan, A. B.; Osbaldeston, G. J.

    1974-01-01

    A 16-year-old boy with systemic mastocytosis from birth had a lifelong history of pronounced diarrhea. Treatment with ingested disodium cromoglycate (DSCG) restored a normal bowel movement pattern and this has been maintained for the six months he has been on treatment. Changes in dosage have repeatedly demonstrated a close relationship between the dose of ingested DSCG and the control of the diarrhea. This case report indicates the potential efficacy of ingested DSCG in the treatment of some gastrointestinal disorders. PMID:4213416

  15. Conjunctival provocation tests with codeine phosphate. Effect of disodium cromoglycate.

    PubMed

    Campbell, A M; Demoly, P; Michel, F B; Bousquet, J

    1993-07-01

    The reactivity of ocular mast cells is poorly characterized in man. Provocation tests with codeine phosphate, a molecule known to activate connective tissue mast cells, were performed in ten normal subjects. Ten-fold increasing concentrations of codeine phosphate (10(-5) to 10(-1) mg/mL) were tested in both eyes until a positive challenge was observed. Schirmer strips were placed under the eyelid and left for five minutes. A negative control was performed ten days later. All subjects had a strongly positive reaction for the same codeine phosphate concentration (10(-1) mg/mL). Histamine was released in 8/10 subjects (control: 7.06 +/- 4.19 nM/L, codeine phosphate: 18.2 +/- 15.7 nM/L, P < .018), PGD2 was released in 8/10 subjects (control: 0 codeine phosphate: 273.3 +/- 408.9 ng/L). Disodium cromoglycate blocked the release of histamine and PGD2. Codeine phosphate is potent at causing mast cell activation in the eye and this effect is blocked by disodium cromoglycate.

  16. A comparative study of the anti-allergic effects of disodium baicalein 6-phosphate (BPS) and disodium cromoglycate (DSCG).

    PubMed

    Koda, A; Watanabe, S; Yanagihara, Y; Nagai, H; Sakamoto, K

    1977-02-01

    A comparative study was carried out on the effects of a soluble derivative of baicalein, disodium baicalein 6-phosphate (BPS) and disodium cromoglycate (DSCG) on the immediate type allergic reactions. BPS not only inhibited reaginic antibody-mediated reactions including antigen-induced mediator release from monkey lung, homologous PCA in rats, and reaginic antibody-mediated degranulation of mast cell, but also non-reaginic antibody-mediated reactions such as mediator release from guinea pig lung sensitized with ovalbumin and that from human lung caused by anti-IgE. The agent, however, did not affect the mediator release from lung of rats sensitized with dinitrophynylated ascaris extract plus Bordetella pertussis. On the other hand, DSCG showed characteristic properties as an inhibitor of reaginic antibody-mediated reaction. It is thus assumed that the functional site of reaginic antibody is well fixed with DSCG at a definite distance between the two-chromone-nuclei while that of IgG is readily fixed with the two molecules of baicalein or BPS.

  17. Identification of isoliquiritigenin as an activator that stimulates the enzymatic production of glycyrrhetinic acid monoglucuronide.

    PubMed

    Wang, Xiaoxue; Wang, Dong; Huo, Yixin; Dai, Dazhang; Li, Chihua; Li, Chun; Liu, Guiyan

    2017-10-02

    Glycyrrhetinic acid monoglucuronide (GAMG) is a great value-added and has considerable commercial interest due to its strong pharmacological activities and functional low-calorie sweetener. However GAMG is quite rare in natural plants, and it must be prepared from glycyrrhizin (GL) by hydrolysing one terminal glucuronic acid. β-Glucuronidase is the key enzyme in the biotransformation of GL to GAMG, but its activities need to be enhanced to facilitate the industrial large-scale production of GAMG. In this study, we identified that isoliquiritigenin (ISL), as one of chemical compositions from the total flavonoids glycyrrhiza (TFG), can significantly enhance β-glucuronidase activity in vitro. Measurements using high-performance liquid chromatography (HPLC) showed that the activity of β-glucuronidase could be increased by 2.66-fold via the addition of ISL to a β-glucuronidase solution that contained GL at a 3:10 molar ratio of ISL to GL. ISL was concluded to be an activator because ISL could reduce the Km and Ea of β-glucuronidase reacting with GL. This study sheds new light on the mechanism of β-glucuronidase and helps to make industrial production of GAMG through fermentation feasible.

  18. A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

    NASA Astrophysics Data System (ADS)

    Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

    2017-03-01

    Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy.

  19. An Overview of Structurally Modified Glycyrrhetinic Acid Derivatives as Antitumor Agents.

    PubMed

    Xu, Bing; Wu, Gao-Rong; Zhang, Xin-Yu; Yan, Meng-Meng; Zhao, Rui; Xue, Nan-Nan; Fang, Kang; Wang, Hui; Chen, Meng; Guo, Wen-Bo; Wang, Peng-Long; Lei, Hai-Min

    2017-06-02

    Glycyrrhetinic Acid (GA), a triterpenoid aglycone component of the natural product glycyrrhizinic acid, was found to possess remarkable anti-proliferative and apoptosis-inducing activity in various cancer cell lines. Though GA was not as active as other triterpenes, such as betulinic acid and oleanolic acid, it could trigger apoptosis in tumor cells and it can be obtained easily and cheaply, which has stimulated scientific interest in using GA as a scaffold to synthesize new antitumor agents. The structural modifications of GA reported in recent decades can be divided into four groups, which include structural modifications on ring-A, ring-C, ring-E and multiple ring modifications. The lack of a comprehensive and recent review on this topic prompted us to gather more new information. This overview is dedicated to summarizing and updating the structural modification of GA to improve its antitumor activity published between 2005 and 2016. We reviewed a total of 210 GA derivatives that we encountered and compiled the most active GA derivatives along with their activity profile in different series. Furthermore, the structure activity relationships of these derivatives are briefly discussed. The included information is expected to be of benefit to further studies of structural modifications of GA to enhance its antitumor activity.

  20. A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy

    PubMed Central

    Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

    2017-01-01

    Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy. PMID:28281678

  1. A Glycyrrhetinic Acid-Modified Curcumin Supramolecular Hydrogel for liver tumor targeting therapy.

    PubMed

    Chen, Guoqin; Li, Jinliang; Cai, Yanbin; Zhan, Jie; Gao, Jie; Song, Mingcai; Shi, Yang; Yang, Zhimou

    2017-03-10

    Curcumin (Cur), a phenolic anti-oxidant compound obtained from Curcuma longa plant, possesses a variety of therapeutic properties. However, it is suffered from its low water solubility and low bioavailability property, which seriously restricts its clinical application. In this study, we developed a glycyrrhetinic acid (GA) modified curcumin supramolecular pro-gelator (GA-Cur) and a control compound Nap-Cur by replacing GA with the naphthylacetic acid (Nap). Both compounds showed good water solubility and could form supramolecular gels by disulfide bond reduction triggered by glutathione (GSH) in vitro. Both formed gels could sustainedly release Cur in buffer solutions. We also investigated the cytotoxicity of pro-gelators to HepG2 cells by a MTT assay and determined the cellular uptake behaviours of them by fluorescence microscopy and LC-MS. Due to the over expression of GA receptor in liver cancer cells, our pro-gelator of GA-Cur showed an enhanced cellular uptake and better inhibition capacity to liver tumor cells than Nap-Cur. Therefore, the GA-Cur could significantly inhibit HepG2 cell growth. Our study provides a novel nanomaterial for liver tumor chemotherapy.

  2. 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

  3. Anti-tumor agents 255: novel glycyrrhetinic acid-dehydrozingerone conjugates as cytotoxic agents.

    PubMed

    Tatsuzaki, Jin; Taniguchi, Masahiko; Bastow, Kenneth F; Nakagawa-Goto, Kyoko; Morris-Natschke, Susan L; Itokawa, Hideji; Baba, Kimiye; Lee, Kuo-Hsiung

    2007-09-15

    Esterification of glycyrrhetinic acid (GA) with dehydrozingerone (DZ) resulted in a novel cytotoxic GA-DZ conjugate. Based on this exciting finding, we conjugated eleven different DZ analogs with GA or other triterpenoids, including oleanoic acid (OA) or ursolic acid (UA). In an in vitro anti-cancer assay using nine different human tumor cell lines, most of the GA-DZ conjugates showed significant potency. Particularly, compounds 5, 29, and 30 showed significant cytotoxic effects against LN-Cap, 1A9, and KB cells with ED(50) values of 0.6, 0.8, and 0.9 microM, respectively. Similar conjugates between DZ and OA or UA were inactive suggesting that the GA component is critical for activity. Notably, although GA-DZ conjugates showed potent cytotoxic activity, the individual components (GA and DZ analogs) were inactive. Thus, GA-DZ conjugates are new chemical entities and represent interesting hits for anti-cancer drug discovery and development.

  4. Disodium cromoglycate in the treatment of chronic proctitis.

    PubMed Central

    Heatley, R V; Calcraft, B J; Rhodes, J; Owen, E; Evans, B K

    1975-01-01

    The effect of topical disodium cromoglycate (DSCG) has been examined in 30 patients with chronic active proctitis using a double-blind crossover trial. Each treatment period was four weeks and patients were given DSCG 200 mg by enema twice daily and 100 mg orally three times each day. Twenty-six patients completed the trial successfully, 14 responded to DSCG treatment, two improved with placebo, and 10 responded to neither. Patients who responded to DSCG had significantly more eosinophils in their rectal biopsies than those who failed to respond and in some instances the counts were very high. The findings support the hypothesis than an allergic reaction is important in the pathogenesis of proctitis. PMID:808445

  5. Cytoprotective effects of disodium cromoglycate on rat stomach mucosa.

    PubMed Central

    Goossens, J.; Van Reempts, J.; Van Wauwe, J. P.

    1987-01-01

    The cytoprotective effects of the anti-asthmatic drug, disodium cromoglycate (DSCG), on gastric mucosal necrosis induced by ethanol in rats were studied. Subcutaneous, but not oral, DSCG prevented the formation of gastric lesions and this effect was dose-dependent between 1.25 and 40 mg kg-1, with an ED50 value of 6.8 mg kg-1. Maximal cytoprotection occurred 15-30 min after DSCG treatment. Histological examination revealed that DSCG effectively protected the gastric mucosa against ethanol-induced vascular congestion, haemorrhage, epithelial desquamation and mucosal oedema. Enhanced production of endogenous prostaglandins, which are known cytoprotective compounds, could not explain the mucosal protection. At a dose of 40 mg kg-1, DSCG did not change prostaglandin E2 or 6-keto-prostaglandin F1 alpha concentrations in gastric mucosal tissue, although its cytoprotective activity was partially inhibited by prior treatment of the animals with indomethacin. Images Figure 2 PMID:3109535

  6. Experimental lead nephropathy: treatment with calcium disodium ethylenediaminetetraacetate.

    PubMed

    Sánchez-Fructuoso, Ana I; Blanco, Julia; Cano, Montserrat; Ortega, Luis; Arroyo, Miguel; Fernández, Christina; Prats, Dolores; Barrientos, Alberto

    2002-07-01

    Chronic lead poisoning may cause hypertension, gout, and renal insufficiency. Most experimental poisoning studies have involved the use of high doses over short periods (ie, acute poisoning). Although chelating treatment leads to remission of acute lead nephropathy, its effects in the treatment of chronic poisoning are unclear. The aims of this study were to evaluate renal alterations produced during chronic lead poisoning and their progression when poisoning was over and to determine the efficiency of chelating treatment with calcium disodium ethylenediaminetetraacetate (EDTA). In this study, 56 male Wistar rats were administered lead in drinking water (500 ppm lead acetate) over 90 days. The control group consisted of 21 nonexposed rats. Seven rats from each group were killed on days 60 and 90. At the end of the 90-day period, 21 of the lead-exposed rats were treated with disodium monocalcium EDTA (50 mg/kg/d x 5 days) intraperitoneally, and 21 were administered serum saline by the same route. Three treatment courses were given separated by 9 days free of treatment. Seven rats from each subgroup were sacrificed at the end of each treatment course. Main findings related to poisoning were hypertrophy and vacuolization of medium and small arteries; mucoid edema and muscular hypertrophy in arterioles; loss of cell brush borders, cell loss, and intranuclear inclusion bodies in the proximal tubule; and fibrosis and the presence of infiltrates in the interstitial component. Treatment with EDTA slowed the progression of most alterations. No damage associated with the use of the chelating agent was observed. Longer term studies of the effects of this drug are required to establish whether the damage caused by lead poisoning may be reversed. Copyright 2002 by the National Kidney Foundation, Inc.

  7. Safety assessment of lauriminodipropionic acid, sodium lauriminodipropionate, and disodium lauriminodipropionate as used in cosmetics.

    PubMed

    Burnett, Christina L; Bergfeld, Wilma F; Belsito, Donald V; Hill, Ronald A; Klaassen, Curtis D; Liebler, Daniel; Marks, James G; Shank, Ronald C; Slaga, Thomas J; Snyder, Paul W; Andersen, F Alan

    2013-01-01

    The Cosmetic Ingredient Review Expert Panel assessed the safety of lauriminodipropionic acid, sodium lauriminodipropionate, and disodium lauriminodipropionate as used in cosmetics. These ingredients function in cosmetics as hair-conditioning agents and surfactant-cleansing agents. The Panel reviewed relevant animal and human data related to the safety of these ingredients in cosmetics. The Panel concluded that lauriminodipropionic acid, sodium lauriminodipropionate, and disodium lauriminodipropionate are safe as cosmetic ingredients in the present practices of use and concentration.

  8. 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.

  9. Novel 18beta-glycyrrhetinic acid analogues as potent and selective inhibitors of 11beta-hydroxysteroid dehydrogenases.

    PubMed

    Su, Xiangdong; Lawrence, Harshani; Ganeshapillai, Dharshini; Cruttenden, Adrian; Purohit, Atul; Reed, Michael J; Vicker, Nigel; Potter, Barry V L

    2004-08-15

    Extensive structural modifications to the 18beta-glycyrrhetinic acid template are described and their effects on the SAR of the 11beta-hydroxysteroid dehydrogenase isozymes type 1 and 2 from the rat are investigated. Isoform selective inhibitors have been discovered and compound 7 N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo-18beta-olean-12-en-30-oic acid amide is highlighted as a very potent selective inhibitor of 11beta-hydroxysteroid dehydrogenase 2 with an IC(50) = 4pM.

  10. Can active components of licorice, glycyrrhizin and glycyrrhetinic acid, lick rheumatoid arthritis?

    PubMed Central

    Huang, Qing-Chun; Wang, Mao-Jie; Chen, Xiu-Min; Yu, Wan-Lin; Chu, Yong-Liang; He, Xiao-Hong; Huang, Run-Yue

    2016-01-01

    OBJECTIVES This review stated the possible application of the active components of licorice, glycyrrhizin (GL) and glycyrrhetinic acid (GA), in rheumatoid arthritis (RA) treatment based on the cyclooxygenase (COX)-2/thromboxane A2 (TxA2) pathway. METHODS The extensive literature from inception to July 2015 was searched in PubMed central, and relevant reports were identified according to the purpose of this study. RESULTS The active components of licorice GL and GA exert the potential anti-inflammatory effects through, at least in part, suppressing COX-2 and its downstream product TxA2. Additionally, the COX-2/TxA2 pathway, an auto-regulatory feedback loop, has been recently found to be a crucial mechanism underlying the pathogenesis of RA. However, TxA2 is neither the pharmacological target of non-steroidal anti-inflammatory drugs (NSAIDs) nor the target of disease modifying anti-rheumatic drugs (DMARDs), and the limitations and side effects of those drugs may be, at least in part, attributable to lack of the effects on the COX-2/TxA2 pathway. Therefore, GL and GA capable of targeting this pathway hold the potential as a novel add-on therapy in therapeutic strategy, which is supported by several bench experiments. CONCLUSIONS The active components of licorice, GL and GA, could not only potentiate the therapeutic effects but also decrease the adverse effects of NSAIDs or DMARDs through suppressing the COX-2/TxA2 pathway during treatment course of RA. PMID:26498361

  11. 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. Copyright © 2015 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

  12. Effects of the gap junction blocker glycyrrhetinic acid on gastrointestinal smooth muscle cells.

    PubMed

    Takeda, Yukari; Ward, Sean M; Sanders, Kenton M; Koh, Sang Don

    2005-04-01

    In the tunica muscularis of the gastrointestinal (GI) tract, gap junctions form low-resistance pathways between pacemaker cells known as interstitial cells of Cajal (ICCs) and between ICC and smooth muscle cells. Coupling via these junctions facilitates electrical slow-wave propagation and responses of smooth muscle to enteric motor nerves. Glycyrrhetinic acid (GA) has been shown to uncouple gap junctions, but previous studies have shown apparent nonspecific effects of GA in a variety of tissues. We tested the effects of GA using isometric force measurements, intracellular microelectrode recordings, the patch-clamp technique, and the spread of Lucifer yellow within cultured ICC networks. In murine small intestinal muscles, beta-GA (10 muM) decreased phasic contractions and depolarized resting membrane potential. Preincubation of GA inhibited the spread of Lucifer yellow, increased input resistance, and decreased cell capacitance in ICC networks, suggesting that GA uncoupled ICCs. In patch-clamp experiments of isolated jejunal myocytes, GA significantly decreased L-type Ca(2+) current in a dose-dependent manner without affecting the voltage dependence of this current. The IC(50) for Ca(2+) currents was 1.9 muM, which is lower than the concentrations used to block gap junctions. GA also significantly increased large-conductance Ca(2+)-activated K(+) currents but decreased net delayed rectifier K(+) currents, including 4-aminopyridine and tetraethylammonium-resistant currents. In conclusion, the reduction of phasic contractile activity of GI muscles by GA is likely a consequence of its inhibitory effects on gap junctions and voltage-dependent Ca(2+) currents. Membrane depolarization may be a consequence of uncoupling effects of GA on gap junctions between ICCs and smooth muscles and inhibition of K(+) conductances in smooth muscle cells.

  13. The effect of glycyrrhetinic acid on pharmacokinetics of cortisone and its metabolite cortisol in rats.

    PubMed

    Lin, Dan; Sun, Wei; Wang, Zhe; Chen, Lian-Guo; Chen, Xiao-Le; Wang, Shuang-Hu; Li, Wan-Shu; Ge, Ren-Shan; Hu, Guo-Xin

    2012-01-01

    The purpose of this paper is to study pharmacokinetics of cortisone (E) and its metabolite cortisol (F) in rats after administration of glycyrrhetinic acid (GA) and cortisone. Healthy male SD rats were randomized to be given 20 mg/kg E or E combined with 10 mg/kg GA. Blood samples were collected at 5, 10, 20, 40, 60, 90, 120, 150, 180, and 240 min after administration. The serum concentrations of E and F were determined by HLPC and pharmacokinetic parameters were calculated using DASver2.0 software. The parameters of AUC((0-t)), AUC((0-∞)), and C(max) for E in the group of E + GA were significantly higher than those in the group of E (P < 0.01); the half-time (t(1/2β)) was extended compared to E (P < 0.05) and CL/F was dropped obviously (P < 0.01). The rise in AUC((0-t)), AUC((0-∞)), and C(max) for cortisol in the group of E + GA was significantly compared to the group of E (P < 0.01). CL/F was lower than E (P < 0.01) and the half-time (t(1/2β)) was slightly extended. In this study, we find that GA restrains the metabolism of E and F and thus increases AUC, t(1/2β), and C(max) of E and F, which may be related to its inhibition effect on 11β-hydroxysteroid dehydrogenase (11β-HSD).

  14. The Effect of Glycyrrhetinic Acid on Pharmacokinetics of Cortisone and Its Metabolite Cortisol in Rats

    PubMed Central

    Lin, Dan; Sun, Wei; Wang, Zhe; Chen, Lian-Guo; Chen, Xiao-Le; Wang, Shuang-Hu; Li, Wan-Shu; Ge, Ren-Shan; Hu, Guo-Xin

    2012-01-01

    The purpose of this paper is to study pharmacokinetics of cortisone (E) and its metabolite cortisol (F) in rats after administration of glycyrrhetinic acid (GA) and cortisone. Healthy male SD rats were randomized to be given 20 mg/kg E or E combined with 10 mg/kg GA. Blood samples were collected at 5, 10, 20, 40, 60, 90, 120, 150, 180, and 240 min after administration. The serum concentrations of E and F were determined by HLPC and pharmacokinetic parameters were calculated using DASver2.0 software. The parameters of AUC(0−t), AUC(0−∞), and Cmax for E in the group of E + GA were significantly higher than those in the group of E (P < 0.01); the half-time (t1/2β) was extended compared to E (P < 0.05) and CL/F was dropped obviously (P < 0.01). The rise in AUC(0−t), AUC(0−∞), and Cmax for cortisol in the group of E + GA was significantly compared to the group of E (P < 0.01). CL/F was lower than E (P < 0.01) and the half-time (t1/2β) was slightly extended. In this study, we find that GA restrains the metabolism of E and F and thus increases AUC, t1/2β, and Cmax of E and F, which may be related to its inhibition effect on 11β-hydroxysteroid dehydrogenase (11β-HSD). PMID:23258958

  15. Synthesis of new glycyrrhetinic acid derived ring A azepanone, 29-urea and 29-hydroxamic acid derivatives as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors.

    PubMed

    Gaware, Rawindra; Khunt, Rupesh; Czollner, Laszlo; Stanetty, Christian; Da Cunha, Thierry; Kratschmar, Denise V; Odermatt, Alex; Kosma, Paul; Jordis, Ulrich; Classen-Houben, Dirk

    2011-03-15

    Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and type 2. Whereas inhibition of 11β-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11β-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. Recently, we published a series of hydroxamic acid derivatives of glycyrrhetinic acid showing high selectivity for 11β-HSD2. The most potent and selective compound is active against human 11β-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11β-HSD1. Starting from the lead compounds glycyrrhetinic acid and the hydroxamic acid derivatives, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11β-HSD1 and 11β-HSD2 in cell lysates. Here we describe novel 29-urea- and 29-hydroxamic acid derivatives of glycyrrhetinic acid as well as derivatives with the Beckman rearrangement of the 3-oxime to a seven-membered ring, and the rearrangement of the C-ring from 11-keto-12-ene to 12-keto-9(11)-ene. The combination of modifications on different positions led to compounds comprising further improved selective inhibition of 11β-HSD2 in the lower nanomolar range with up to 3600-fold selectivity.

  16. Columnar molecular aggregation in the aqueous solutions of disodium cromoglycate.

    PubMed

    Agra-Kooijman, Dena M; Singh, Gautam; Lorenz, Alexander; Collings, Peter J; Kitzerow, Heinz-S; Kumar, Satyendra

    2014-06-01

    Stack, chimneylike, and threadlike assemblies have previously been proposed for the structure of disodium cromoglycate (DSCG) aggregates in aqueous solutions. The results of the synchrotron x-ray scattering investigations reported here reveal the formation of simple columnar assemblies with π-π stacking at a separation of 3.4 Å between the DSCG molecules. Lateral separation between the assemblies is concentration and temperature dependent, varying from ∼35 to 42 Å in the orientationally ordered nematic (N) phase and from 27 to 32 Å in the columnar or middle (M) phase having long range lateral positional order. The assemblies' length depends on concentration and consists of ∼23 molecules in the N phase, becoming three to ten times larger in the M phase. The scission energy is concentration dependent in the N phase with values ∼7.19 ± 0.14 k_{B}T (15 wt %), 2.73 ± 0.4 k_{B}T (20 wt %), and 3.05 ± 0.2 k_{B}T (25 wt %). Solutions of all concentrations undergo a spinodal decomposition at temperatures above ∼40 °C, resulting in DSCG-rich regions with the M phase and water-rich regions in the N and isotropic phases.

  17. Columnar molecular aggregation in the aqueous solutions of disodium cromoglycate

    NASA Astrophysics Data System (ADS)

    Agra-Kooijman, Dena M.; Singh, Gautam; Lorenz, Alexander; Collings, Peter J.; Kitzerow, Heinz-S.; Kumar, Satyendra

    2014-06-01

    Stack, chimneylike, and threadlike assemblies have previously been proposed for the structure of disodium cromoglycate (DSCG) aggregates in aqueous solutions. The results of the synchrotron x-ray scattering investigations reported here reveal the formation of simple columnar assemblies with π-π stacking at a separation of 3.4 Å between the DSCG molecules. Lateral separation between the assemblies is concentration and temperature dependent, varying from ˜35 to 42 Å in the orientationally ordered nematic (N) phase and from 27 to 32 Å in the columnar or middle (M) phase having long range lateral positional order. The assemblies' length depends on concentration and consists of ˜23 molecules in the N phase, becoming three to ten times larger in the M phase. The scission energy is concentration dependent in the N phase with values ˜7.19 ± 0.14 kBT (15 wt %), 2.73 ± 0.4 kBT (20 wt %), and 3.05 ± 0.2 kBT (25 wt %). Solutions of all concentrations undergo a spinodal decomposition at temperatures above ˜40 °C, resulting in DSCG-rich regions with the M phase and water-rich regions in the N and isotropic phases.

  18. Combretastatin A4 disodium phosphate-induced myocardial injury

    PubMed Central

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

    2016-01-01

    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. Synthesis and properties of disodium tetraethyleneglycol-bis-(alpha-carboxybenzylpenicillin).

    PubMed

    Kim, Y T; Jung, Y J; Kim, Y M

    1999-04-01

    Disodium tetraethyleneglycol-bis-(alpha-carboxybenzylpenicillin) (TEG-carbenicillin), a tetraethyleneglycol (TEG) diester of carbenicillin, was synthesized to develop a carbenicillin prodrug with enhanced acid stability for oral administration. Antimicrobial activities of TEG-carbenicillin tested against gram-negative Escherichia coli (TG-1) and gram-positive Staphylococcus aureus (ATCC-12228) and Bacillus subtilis (NA-1) were comparable to that of carbenicillin. Stability of the beta-lactam ring of TEG-carbenicillin was determined by iodometry at pH 6.8, pH 4.5, and pH 2.0 at varied time intervals and was compared to that of carbenicillin. In 26 hr, both of the compounds were stable at pH 6.8. At pH 4.5, about 41% of the carbenicillin was decomposed, while TEG-carbenicillin was not appreciably decomposed. At pH 2.0, carbenicillin was decomposed about 61% after 6 hr, while TEG-carbenicillin was decomposed about 21% during the same period.

  20. Pharmacokinetics of disodium-fosfomycin in mongrel dogs.

    PubMed

    Gutierrez, O L; Ocampo, C L; Aguilera, J R; Luna, J; Sumano, L H

    2008-08-01

    Pharmacokinetic variables of fosfomycin were determined after administration of buffered disodium-fosfomycin intravenously (IV), intramuscularly (IM), subcutaneously (SC) and orally (PO), in mongrel dogs, at 40 and 80 mg/kgday for three days. Renal integrity was also assessed by measuring key serum variables. Day 1, day 2 and day 3 plasma concentration vs. time profiles were undistinguishable, but there appears to be a lineal increase in serum concentrations vs. time with the dose. A non-accumulative kinetic behavior was observed after three days with both doses and most pharmacokinetic variables remain unaltered. Considering a MIC range from 1 mirog/mL to 16 microg/mL of fosfomycin in serum for sensitive bacteria, and a negligible plasma protein binding of fosfomycin (<0.5%), useful plasma concentrations can only be achieved after the SC injection of 80 mg/kg every 12h, having a C(max)=18.96+/-0.3 microg/mL; a T(1/2beta)=2.09+/-0.06 microg/mL and a bioavailability of 84-85%. No alterations were observed in serum variables of kidney-related biochemical values.

  1. Glycyrrhetinic acid might increase the nephrotoxicity of bakuchiol by inhibiting cytochrome P450 isoenzymes

    PubMed Central

    Zhao, Zijing; Yuan, Mei

    2016-01-01

    Background Licorice, a popular traditional Chinese medicine (TCM), is widely used to moderate the effects (detoxification) of other herbs in TCM and often combined with Fructus Psoraleae. However, the classical TCM book states that Fructus Psoraleae is incompatible with licorice; the mechanism underlying this incompatibility has not been identified. Glycyrrhetinic acid (GA), the active metabolite of licorice, may increase the toxicity of bakuchiol (BAK), the main chemical ingredient in Psoralea corylifolia, by inhibiting its detoxification enzymes CYP450s. Methods The effect of concomitant GA administration on BAK-induced nephrotoxicity was investigated, and the metabolic interaction between BAK and GA was further studied in vitro and in vivo. The cytotoxicity was assessed using an MTT assay in a co-culture model of HK-2 cell and human liver microsomes (HLMs). The effect of GA on the metabolism of BAK, and on the activities of CYP isoforms were investigated in HLMs. The toxicokinetics and tissue exposure of BAK as well as the renal and hepatic functional markers were measured after the administration of a single oral dose in rats. Results In vitro studies showed that the metabolic detoxification of BAK was significantly reduced by GA, and BAK was toxic to HK-2 cells, as indicated by 25∼40% decreases in viability when combined with GA. Further investigation revealed that GA significantly inhibited the metabolism of BAK in HLMs in a dose-dependent manner. GA strongly inhibits CYP3A4 and weakly inhibits CYP2C9 and CYP1A2; these CYP isoforms are involved in the metabolism of BAK. In vivo experiment found that a single oral dose of BAK combined with GA or in the presence of 1-aminobenzotriazole (ABT), altered the toxicokinetics of BAK in rats, increased the internal exposure, suppressed the elimination of BAK prototype, and therefore may have enhanced the renal toxicity. Conclusion The present study demonstrated that GA inhibits CYP isoforms and subsequently may

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Synthesis and physicochemical characterization of the impurities of pemetrexed disodium, an anticancer drug.

    PubMed

    Michalak, Olga; Gruza, Mariusz M; Witkowska, Anna; Bujak, Iwona; Cmoch, Piotr

    2015-05-29

    A physicochemical characterization of the process-related impurities associated with the synthesis of pemetrexed disodium was performed. The possibility of pemetrexed impurities forming has been mentioned in literature, but no study on their structure has been published yet. This paper describes the development of the synthesis methods for these compounds and discusses their structure elucidation on the basis of two-dimensional NMR experiments and MS data. The identification of these impurities should be useful for the quality control during the production of the pemetrexed disodium salt.

  7. Bronchodilator effect of disodium cromoglycate administered as a dry powder in exercise induced asthma.

    PubMed Central

    Horn, C R; Jones, R M; Lee, D; Brennan, S R

    1984-01-01

    A double-blind, placebo controlled study of the effects of disodium cromoglycate (DSCG), administered as a dry powder via the spinhaler, in established exercise-induced asthma, was carried out. DSCG resulted in an increase in the rate of recovery compared with placebo. The findings confirm that DSCG has bronchodilator properties. PMID:6439234

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false L-Glutamic acid, N-(1-oxododecyl... Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  9. 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false L-Glutamic acid, N-(1-oxododecyl... Specific Chemical Substances § 721.3820 L-Glutamic acid, N-(1-oxododecyl)-, disodium salt. (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified as L-Glutamic...

  11. [Effects of penetration enhancers on in vitro percutaneous absorption and amount retained in skin of paeonol, dictamnine, fraxinellone and glycyrrhetinic acid in Liangfu cream].

    PubMed

    Wang, Sen; Zhu, Weifeng; Ou, Shuiping; Guan, Yongmeii; Chen, Lihua; Yang, Ming

    2009-07-01

    To study the effects of different penetration enhancers on the in vitro percutaneous absorption and amount retained in skin of active ingredients in Liangfu cream and to screen out the effective accelerator. Using improved Franz-type difusion cell and excised small mouse skin in vitro as transdermal barrier, the amount retained in skin and kinetics parameters of active ingredients such as cumulative permeation quantity, permeation rate and permeation lagged time were determined by HPLC. The enhancement ability of four different enhancers such as azone, oleic acid, transcutol P and isopropyl myristate were investigated. 3% IPM enhanced the cumulative permeation quantity better than other penetration enhancers. The enhancive permeation multiples of paeonol, dictamnine, fraxinellone and glycyrrhetinic acid were 1.52, 1.24, 1.73 and 3.21 times (P < 0.05). The enhancive amount retained in skin multiple of glycyrrhetinic acid was 1.96 times (P < 0.05), but for other components there were no significant impacts. The effects of penetration enhancers on the in vitro percutaneous absorption and amount retained in skin of components in Liangfu cream are different. 3% IPM which can enhance the cumulative permeation quantity of four components and amount retained in skin of glycyrrhetinic acid is the most suitable penetration enhancer for Liangfu cream.

  12. Effect of Disodium Cromoglycate (DSCG) and Antihistamines on Postirradiation Cerebral Blood Flow and Plasma Levels of Histamine and Neurotensin

    DTIC Science & Technology

    1988-01-01

    73 6 SOTI UNCLASIFIE ESCURIIY CLASSIFICATION OF Tm-S siki FUNDAMENTAL AND APPLIED TOXICOLOGY 10, 233-242 (1988) Effect of Disodium Cromoglycate ( DSCG ...occur ment with the mast cell stabilizer, disodium with equal frequency in all species, having cromoglycate ( DSCG , cromolyn sodium), in- been reported...animals exposed to doses In the present study we attempt to evaluate of 100-300 Gy (Pitchford, 1968). A recent further the effect of DSCG on radiation

  13. 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

  14. Synthesis, characterization and liver targeting evaluation of self-assembled hyaluronic acid nanoparticles functionalized with glycyrrhetinic acid.

    PubMed

    Wang, Xiaodan; Gu, Xiangqin; Wang, Huimin; Sun, Yujiao; Wu, Haiyang; Mao, Shirui

    2017-01-01

    Recently, polymeric materials with multiple functions have drawn great attention as the carrier for drug delivery system design. In this study, a series of multifunctional drug delivery carriers, hyaluronic acid (HA)-glycyrrhetinic acid (GA) succinate (HSG) copolymers were synthesized via hydroxyl group modification of hyaluronic acid. It was shown that the HSG nanoparticles had sub-spherical shape, and the particle size was in the range of 152.6-260.7nm depending on GA graft ratio. HSG nanoparticles presented good short term and dilution stability. MTT assay demonstrated all the copolymers presented no significant cytotoxicity. In vivo imaging analysis suggested HSG nanoparticles had superior liver targeting efficiency and the liver targeting capacity was GA graft ratio dependent. The accumulation of DiR (a lipophilic, NIR fluorescent cyanine dye)-loaded HSG-6, HSG-12, and HSG-20 nanoparticles in liver was 1.8-, 2.1-, and 2.9-fold higher than that of free DiR. The binding site of GA on HA may influence liver targeting efficiency. These results indicated that HSG copolymers based nanoparticles are potential drug carrier for improved liver targeting.

  15. In silico and in vivo anti-malarial studies of 18β glycyrrhetinic acid from Glycyrrhiza glabra.

    PubMed

    Kalani, Komal; Agarwal, Jyoti; Alam, Sarfaraz; Khan, Feroz; Pal, Anirban; Srivastava, Santosh Kumar

    2013-01-01

    Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69 µg/ml) anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68-100% at doses of 62.5-250 mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress.

  16. Effects of oils and emulsifiers on the skin penetration of stearyl glycyrrhetinate in oil-in-water emulsions.

    PubMed

    Sakata, Osamu; Fujii, Makiko; Koizumi, Naoya; Nakade, Masato; Kameyama, Koichi; Watanabe, Yoshiteru

    2014-01-01

    We investigated whether an emulsifier or an emulsified oil affects the skin penetration of stearyl glycyrrhetinate (SG) when it is applied in an oil-in-water (O/W)-type emulsion under finite dose conditions in vitro. SG has a high molecular weight (MW: 723) and high lipophilicity (log P: 15.6). Skin penetration of SG applied with O/W emulsions was evaluated using 6 types of emulsifiers that are commonly used in cosmetics; however, no significant differences were observed between these emulsifiers. When applied with liquid paraffins in oil phase, SG skin penetration increased significantly as the molecular weight of the liquid paraffin decreased. The skin penetration of the fluorescent dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI; MW: 834, log P: 23.2) also increased with O/W-type emulsions containing liquid paraffins of lower molecular weights. These results indicate that use of O/W-type emulsions with an appropriate oil phase can improve SG skin penetration.

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

    PubMed

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

    2016-02-23

    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,(1)H 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 (25 kDa) 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.

  18. 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

  19. 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.

  20. An EPR and optical absorption study of Cu(2+) doped in disodium malonate trihydrate single crystal.

    PubMed

    Yarbaşi, Zeynep; Karabulut, Bünyamin; Karabulut, Abdulhalik

    2009-03-01

    Single crystals and powder electron paramagnetic resonance (EPR) studies of Cu(2+)-doped disodium malonate trihydrate [C(3)H(2)O(4)Na(2).3H(2)O] have been carried out at room temperature. The angular variation of the disodium malonate trihydrate single crystal have shown that two different Cu(2+) complexes are located in different chemical environments, and each environment contains one magnetically inequivalent Cu(2+) sites in distinct orientations occupying substitutional positions in the lattice and show very high angular dependence. The principal values of the g and the hyperfine tensors were determined and were found to be in agreement with the literature values. Crystal field around the Cu(2+) ion is nearly rhombic. The optical absorption studies show two bands at 603nm (16584cm(-1)) and 890nm (11236cm(-1)) which confirm the rhombic symmetry. The crystals field parameters and than the wave function are determined.

  1. An EPR and optical absorption study of Cu 2+ doped in disodium malonate trihydrate single crystal

    NASA Astrophysics Data System (ADS)

    Yarbaşı, Zeynep; Karabulut, Bünyamin; Karabulut, Abdulhalik

    2009-03-01

    Single crystals and powder electron paramagnetic resonance (EPR) studies of Cu 2+-doped disodium malonate trihydrate [C 3H 2O 4Na 2·3H 2O] have been carried out at room temperature. The angular variation of the disodium malonate trihydrate single crystal have shown that two different Cu 2+ complexes are located in different chemical environments, and each environment contains one magnetically inequivalent Cu 2+ sites in distinct orientations occupying substitutional positions in the lattice and show very high angular dependence. The principal values of the g and the hyperfine tensors were determined and were found to be in agreement with the literature values. Crystal field around the Cu 2+ ion is nearly rhombic. The optical absorption studies show two bands at 603 nm (16584 cm -1) and 890 nm (11236 cm -1) which confirm the rhombic symmetry. The crystals field parameters and than the wave function are determined.

  2. Deaths resulting from hypocalcemia after administration of edetate disodium: 2003-2005.

    PubMed

    Brown, Mary Jean; Willis, Teresa; Omalu, Bennet; Leiker, Richard

    2006-08-01

    From 2003 to 2005, deaths of 3 individuals as a result of cardiac arrest caused by hypocalcemia during chelation therapy were reported to the Centers for Disease Control and Prevention. Two were children, both of whom were treated with edetate disodium. At the time of this writing, the adult case was still under investigation. No previous cases of death resulting from hypocalcemia during chelation have been reported. From our experience and review of the literature, we suggest that health care providers who are unfamiliar with chelation consult an expert before undertaking treatment and that hospital formularies evaluate whether stocking edetate disodium is necessary, given the risk for hypocalcemia and the availability of less toxic alternatives.

  3. Disodium zinc bis­(sulfate) tetra­hydrate (zinc astrakanite) revisited

    PubMed Central

    Díaz de Vivar, M. Enriqueta; Baggio, Sergio; Ibáñez, Andrés; Baggio, Ricardo

    2008-01-01

    We present a new low-temperature refinement of disodium zinc bis­(sulfate) tetra­hydrate {systematic name: poly[tetra-μ-aqua-di-μ-sulfato-zinc(II)disodium(I)]}, [Na2Zn(SO4)2(H2O)4]n or Zn astrakanite, which is an upgrade of previously reported data [Bukin & Nozik (1974 ▶). Zh. Strukt. Khim. 15, 712–716]. The compound is part of an isostructural family containing the Mg (the original astrakanite mineral), Co and Ni species. The very regular ZnO(aqua)4O(sulfate)2 octa­hedra lie on centres of symmetry, while the rather distorted NaO(aqua)2O(sulfate)4 octa­hedra appear at general positions, linked into a three-dimensional network by the bridging water mol­ecules and the fully coordinated sulfate groups. PMID:21202433

  4. Chirality Sensing and Size Discrimination of Anions by Macrotricyclic Cyclen–Disodium Complexes**

    PubMed Central

    Ito, Hiroshi; Shinoda, Satoshi

    2014-01-01

    Two macrotricyclic ligands composed of two face-to-face octadentate metal chelates were synthesized. These cage-shaped disodium complexes had special recognition ability for various counter anions. Specific chiral dicarboxylates bound to the complexes within the cavity and exhibited chirality induction properties. For instance, N-Boc-Asp dianion strongly induced circular dichroism (CD) signals, but N-Boc-Glu dianion, which is one carbon longer, did not.

  5. Chromolithic method development, validation and system suitability analysis of ultra-sound assisted extraction of glycyrrhizic acid and glycyrrhetinic acid from Glycyrrhiza glabra.

    PubMed

    Gupta, Suphla; Sharma, Rajni; Pandotra, Pankaj; Jaglan, Sundeep; Gupta, Ajai Prakash

    2012-08-01

    An ultrasound-assisted extraction and chromolithic LC method was developed for simultaneous determination of glycyrrhizic acid (GA) and glycyrrhetinic acid (GL) from the root extract of Glycyrrhizza glabra using RPLC-PDA. The developed method was validated according to the International Conference on Harmonisation. The method exhibited good linearity (r2 > 0.9989) with high precision and achieved good accuracies between 97.5 to 101.3% of quantitative results. The method is more sensitive and faster (resolved within ten minutes) than the earlier developed methods using normal LC columns.

  6. A novel 18 beta-glycyrrhetinic acid analogue as a potent and selective inhibitor of 11 beta-hydroxysteroid dehydrogenase 2.

    PubMed

    Vicker, Nigel; Su, Xiangdong; Lawrence, Harshani; Cruttenden, Adrian; Purohit, Atul; Reed, Michael J; Potter, Barry V L

    2004-06-21

    Using 18beta-glycyrrhetinic acid as a template, the synthesis of a series of secondary amides at the 30-position is described and the effects of these modifications on the SAR of the 11beta-hydroxysteroid dehydrogenase isozymes type 1 and 2 from the rat are investigated. An isoform selective inhibitor has been discovered and compound 5, N-(2-hydroxyethyl)-3beta-hydroxy-11-oxo-18beta-olean-12-en-30-oic acid amide, is highlighted as a very potent and selective inhibitor of 11beta-hydroxysteroid dehydrogenase 2 with an IC(50)=4 pM.

  7. Synthesis of novel 2-cyano substituted glycyrrhetinic acid derivatives as inhibitors of cancer cells growth and NO production in LPS-activated J-774 cells.

    PubMed

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

    2014-01-01

    Here we report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring glycyrrhetinic acid bearing a 2-cyano-3-oxo-1-en moiety in the A-ring and double bonds and carbonyl groups in the C, D and E rings. Bioassays using murine macrophage-like and tumor cells show that compound 4, which differs from Soloxolone methyl by the absence of a 9(11)-double bond in the C-ring, displays anti-inflammatory and inhibitory activities with respect to tumor cells with a high selectivity index value. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. 18β-Glycyrrhetinic Acid Suppresses Cell Proliferation through Inhibiting Thromboxane Synthase in Non-Small Cell Lung Cancer

    PubMed Central

    Huang, Qing-Chun; Chen, Xiu-Min; Jiang, Ze-Bo; Zhang, Xian; Zeng, Xing

    2014-01-01

    18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice. The anti-cancer activity of 18β-GA has been studied in many cancer types, whereas its effects in lung cancer remain largely unknown. We first showed that 18β-GA effectively suppressed cell proliferation and inhibited expression as well as activity of thromboxane synthase (TxAS) in non-small cell lung cancer (NSCLC) cells A549 and NCI-H460. In addition, the administration of 18β-GA did not have any additional inhibitory effect on the decrease of cell proliferation induced by transfection with TxAS small interference RNA (siRNA). Moreover, 18β-GA failed to inhibit cell proliferation in the immortalized human bronchial epithelial cells 16HBE-T and another NSCLC cell line NCI-H23, both of which expressed minimal level of TxAS as compared to A549 and NCI-H460. However, 18β-GA abolished the enhancement of cell proliferation induced by transfection of NCI-H23 with pCMV6-TxAS plasmid. Further study found that the activation of both extracellular signal-regulated kinase (ERK)1/2 and cyclic adenosine monophosphate response element binding protein (CREB) induced by TxAS cDNA transfection could be totally blocked by 18β-GA. Altogether, we have delineated that, through inhibiting TxAS and its initiated ERK/CREB signaling, 18β-GA suppresses NSCLC cell proliferation. Our study has highlighted the significance of 18β-GA with respect to prevention and treatment of NSCLC. PMID:24695790

  9. Inhibition of human and rat 11beta-hydroxysteroid dehydrogenase type 1 by 18beta-glycyrrhetinic acid derivatives.

    PubMed

    Su, Xiangdong; Vicker, Nigel; Lawrence, Harshani; Smith, Andrew; Purohit, Atul; Reed, Michael J; Potter, Barry V L

    2007-05-01

    11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) plays an important role in regulating the cortisol availability to bind to corticosteroid receptors within specific tissue. Recent advances in understanding the molecular mechanisms of metabolic syndrome indicate that elevation of cortisol levels within specific tissues through the action of 11beta-HSD1 could contribute to the pathogenesis of this disease. Therefore, selective inhibitors of 11beta-HSD1 have been investigated as potential treatments for metabolic diseases, such as diabetes mellitus type 2 or obesity. Here we report the discovery and synthesis of some 18beta-glycyrrhetinic acid (18beta-GA) derivatives (2-5) and their inhibitory activities against rat hepatic11beta-HSD1 and rat renal 11beta-HSD2. Once the selectivity over the rat type 2 enzyme was established, these compounds' ability to inhibit human 11beta-HSD1 was also evaluated using both radioimmunoassay (RIA) and homogeneous time resolved fluorescence (HTRF) methods. The 11-modified 18beta-GA derivatives 2 and 3 with apparent selectivity for rat 11beta-HSD1 showed a high percentage inhibition for human microsomal 11beta-HSD1 at 10 microM and exhibited IC50 values of 400 and 1100 nM, respectively. The side chain modified 18beta-GA derivatives 4 and 5, although showing selectivity for rat 11beta-HSD1 inhibited human microsomal 11beta-HSD1 with IC50 values in the low micromolar range.

  10. 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

  11. 18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures

    PubMed Central

    Papaevgeniou, Nikoletta; Sakellari, Marianthi; Jha, Sweta; Tavernarakis, Nektarios; Holmberg, Carina I.; Gonos, Efstathios S.

    2016-01-01

    Abstract Aims: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression. Results: Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment. Innovation: This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism. Conclusion: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet. Antioxid. Redox Signal. 25, 855–869. PMID:26886723

  12. 18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts.

    PubMed

    Hung, Chi-Feng; Hsiao, Chien-Yu; Hsieh, Wen-Hao; Li, Hsin-Ju; Tsai, Yi-Ju; Lin, Chun-Nan; Chang, Hsun-Hsien; Wu, Nan-Lin

    2017-01-01

    Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.

  13. In Vitro and in Vivo Inhibitory Effects of Glycyrrhetinic Acid in Mice and Human Cytochrome P450 3A4.

    PubMed

    Lv, Qiao-Li; Wang, Gui-Hua; Chen, Shu-Hui; Hu, Lei; Zhang, Xue; Ying, Guo; Qin, Chong-Zhen; Zhou, Hong-Hao

    2015-12-25

    Glycyrrhetinic acid (GA) has been used clinically in the treatment of patients with chronic hepatitis. This study evaluated the effect of GA on the activity of five P450(CYP450) cytochrome enzymes: CYP2A6, CYP2C9, CYP2C19, CYP2D6, and CYP3A4, in human liver microsomes (HLMs) and recombinant cDNA-expressed enzyme systems using a HPLC-MS/MS CYP-specific probe substrate assay. With midazolam as the probe substrate, GA greatly decreased CYP3A4 activity with IC50 values of 8.195 μM in HLMs and 7.498 μM in the recombinant cDNA-expressed CYP3A4 enzyme system, respectively. It significantly decreased CYP3A4 activity in a dose- but not time-dependent manner. Results from Lineweaver-Burk plots showed that GA could inhibit CYP3A4 activity competitively, with a Ki value of 1.57 μM in HLMs. Moreover, CYP2C9 and CYP2C19 could also be inhibited significantly by GA with IC50 of 42.89 and 40.26 μM in HLMs, respectively. Other CYP450 isoforms were not markedly affected by GA. The inhibition was also confirmed by an in vivo study of mice. In addition, it was observed that mRNA expressions of the Cyps2c and 3a family decreased significantly in the livers of mice treated with GA. In conclusion, this study indicates that GA may exert herb-drug interactions by competitively inhibiting CYP3A4.

  14. Synthesis of glycyrrhetinic acid-modified chitosan 5-fluorouracil nanoparticles and its inhibition of liver cancer characteristics in vitro and in vivo.

    PubMed

    Cheng, Mingrong; Gao, Xiaoyan; Wang, Yong; Chen, Houxiang; He, Bing; Xu, Hongzhi; Li, Yingchun; Han, Jiang; Zhang, Zhiping

    2013-09-17

    Nanoparticle drug delivery (NDDS) is a novel system in which the drugs are delivered to the site of action by small particles in the nanometer range. Natural or synthetic polymers are used as vectors in NDDS, as they provide targeted, sustained release and biodegradability. Here, we used the chitosan and hepatoma cell-specific binding molecule, glycyrrhetinic acid (GA), to synthesize glycyrrhetinic acid-modified chitosan (GA-CTS). The synthetic product was confirmed by Fourier transformed infrared spectroscopy (FT-IR) and ¹H-nuclear magnetic resonance (¹H-NMR). By combining GA-CTS and 5-FU (5-fluorouracil), we obtained a GA-CTS/5-FU nanoparticle, with a particle size of 217.2 nm, a drug loading of 1.56% and a polydispersity index of 0.003. The GA-CTS/5-FU nanoparticle provided a sustained release system comprising three distinct phases of quick, steady and slow release. We demonstrated that the nanoparticle accumulated in the liver. In vitro data indicated that it had a dose- and time-dependent anti-cancer effect. The effective drug exposure time against hepatic cancer cells was increased in comparison with that observed with 5-FU. Additionally, GA-CTS/5-FU significantly inhibited the growth of drug-resistant hepatoma, which may compensate for the drug-resistance of 5-FU. In vivo studies on an orthotropic liver cancer mouse model demonstrated that GA-CTS/5-FU significantly inhibited tumor growth, resulting in increased survival time.

  15. Synthesis of novel 3-amino and 29-hydroxamic acid derivatives of glycyrrhetinic acid as selective 11β-hydroxysteroid dehydrogenase 2 inhibitors.

    PubMed

    Stanetty, Christian; Czollner, Laszlo; Koller, Iris; Shah, Priti; Gaware, Rawindra; Cunha, Thierry Da; Odermatt, Alex; Jordis, Ulrich; Kosma, Paul; Classen-Houben, Dirk

    2010-11-01

    Glycyrrhetinic acid, the metabolite of the natural product glycyrrhizin, is a well known nonselective inhibitor of 11β-hydroxysteroid dehydrogenase (11β-HSD) type 1 and type 2. Whereas inhibition of 11β-HSD1 is currently under consideration for treatment of metabolic diseases, such as obesity and diabetes, 11β-HSD2 inhibitors may find therapeutic applications in chronic inflammatory diseases and certain forms of cancer. So far, no selective 11β-HSD2 inhibitor has been developed and neither animal studies nor clinical trials have been reported based on 11β-HSD2 inhibition. Starting from the lead compound glycyrrhetinic acid, novel triterpene type derivatives were synthesized and analyzed for their biological activity against overexpressed human 11β-HSD1 and 11β-HSD2 in cell lysates. Several hydroxamic acid derivatives showed high selectivity for 11β-HSD2. The most potent and selective compound is active against human 11β-HSD2 in the low nanomolar range with a 350-fold selectivity over human 11β-HSD1.

  16. Design, synthesis and in vitro evaluation of 18β-glycyrrhetinic acid derivatives for anticancer activity against human breast cancer cell line MCF-7.

    PubMed

    Yadav, Dharmendra Kumar; Kalani, Komal; Singh, Abhishek K; Khan, Feroz; Srivastava, Santosh K; Pant, Aditya B

    2014-01-01

    In the present work, QSAR model was derived by multiple linear regression method for the prediction of anticancer activity of 18β-glycyrrhetinic acid derivatives against the human breast cancer cell line MCF-7. The QSAR model for anti-proliferative activity against MCF-7 showed high correlation (r(2)=0.90 and rCV(2)=0.83) and indicated that chemical descriptors namely, dipole moment (debye), steric energy (kcal/mole), heat of formation (kcal/mole), ionization potential (eV), LogP, LUMO energy (eV) and shape index (basic kappa, order 3) correlate well with activity. The QSAR virtually predicted that active derivatives were first semi-synthesized and characterized on the basis of their (1)H and (13)C NMR spectroscopic data and then were in-vitro tested against MCF-7 cancer cell line. In particular, octylamide derivative of glycyrrhetinic acid GA-12 has marked cytotoxic activity against MCF-7 similar to that of standard anticancer drug paclitaxel. The biological assays of active derivative selected by virtual screening showed significant experimental activity.

  17. Enhancement by reproterol of the ability of disodium cromoglycate to stabilize rat mastocytes.

    PubMed

    Eleno, N; Gajate, E; Macias, J; Garay, R P

    1999-01-01

    The beta2-adrenoceptor agonist reproterol and disodium cromoglycate (DSCG) are used in fixed combination for the treatment of asthma, because they act on bronchial smooth muscle and inflammatory cells, respectively. Here, we investigated if reproterol can also act in rat mast cells in vitro to facilitate the inhibitory action of disodium cromoglycate (DSCG) on histamine secretion induced by compound 48/80. Reproterol was as potent as DSCG to inhibit histamine release in rat mast cells (32.8+/-6.0 vs. 36.7+/-6.2% at 1 microM of each compound, n=10 and n=8 respectively). Mast cell stabilization by DSCG (1-100 microM) was strongly and significantly enhanced in the presence of a fixed saturating concentration of reproterol (100 microM). Conversely, the combination of DSCG (1-100 microM) with the beta2-agonist used as reference compound, salbutamol (100 microM) did not inhibit histamine release more than DSCG alone. In combination with a saturating concentration of DSCG (100 microM), reproterol inhibited histamine release more than reproterol alone. The potent adenylate cyclase stimulator forskolin (50 microM) was able to inhibit histamine release to a similar extent as DSCG and significantly (P<0.05) enhanced the inhibition of histamine release by DSCG. Finally, the phosphodiesterase inhibitor theophylline (100 microM) was equipotent to reproterol and DSCG in stabilizing rat mast cells. In conclusion, reproterol enhances the ability of disodium cromoglycate to stabilize rat mast cells. This effect is not shared by salbutamol and can be, at least in part, independent of beta2-adrenoceptor stimulation. Copyright 1999 Academic Press.

  18. A double-blind trial comparing disodium cromoglycate (DSCG), and ketotifen in extrinsic asthmatic children.

    PubMed

    Schuhl, J F; Holgado de Cuesta, D

    1981-07-01

    A double-blind non crossover trial comparing disodium cromoglycate (DSCG), with ketotifen, was carried out in twenty-seven extrinsic asthmatic children over 12 weeks. Assessment was made using symptom score and drug score charts. Both drugs showed a similar protective effect in the group studied. None of the subjects had to withdraw from the trial and no side-effects were noted in weight-curve, arterial pressure and pulse rate. PEFR values remained unchanged for both drugs throughout the trial. A non-significant tendency for additional corticosteroid support in the Ketotifen group was noted.

  19. Effect of disodium cromoglycate on antigen-evoked histamine release from human skin

    PubMed Central

    Pearce, Cheryl A.; Greaves, M. W.; Plummer, Valerie M.; Yamamoto, S.

    1974-01-01

    The effect of disodium cromoglycate (DSCG) on antigen-evoked histamine release from IgE-sensitized human skin in vitro has been studied using breast skin from six donors. Concentrations of DSCG ranging from 10–200 μM did not produce any consistent effect on histamine release, the results ranging from moderate inhibition to moderate enhancement. With higher concentrations of DSCG (400–500 μM) enhancement of release occurred in nearly all experiments. Variation of antigen concentration did not modify the response to DSCG. These results do not support the possibility that DSCG may be effective in the treatment of immediate hypersensitivity reactions in human skin. PMID:4143251

  20. Inhibition of immediate hypersensitivity reactions in the rat by disodium cromoglycate and nitroindanedione.

    PubMed Central

    Spicer, B A; Ross, J W; Smith, H

    1975-01-01

    A nitroindanedione (BRL 10833) and disodium cromoglycate (DSCG) showed similar activities as inhibitors of IgE-mediated passive cutaneous anaphylaxis (PCA) and passive peritoneal anaphylaxis (PPA) reactions in the rat. BRL 10833 was more active than DSCG when given parenterally and unlike DSCG it inhibited the PCA reaction in the rat after oral administration. In the PCA test both compounds produced a state of refractoriness both to themselves and to each other. Isoprenaline also inhibited the PCA reaction but its activity was not reduced when the rats were refractory to DSCG. PMID:812623

  1. [Disodium cromoglycate--mast cell degranulation blocker in the process of tissue remodelation].

    PubMed

    Maxová, H; Vasilková, M; Tkaczyk, J; Vízek, M

    2010-01-01

    Disodium cromoglycate (DSCG) is a compound commonly used in the treatment of allergic diseases. The effect of DSCG is due to its ability to stabilize the mast cell membrane and to prevent release of histamine and inflammatory mediators. Mast cells are also an abundant source of tissue metalloproteinases, serine proteases and growth factors, which play an important role in the processes of the tissue remodeling. In this view the DSCG is a substance which allows us to study the mechanisms of the pulmonary vascular bed remodeling in the experimental animals exposed to chronic hypoxia and in a phase of the recovery from hypoxia.

  2. The inhibition by dexamethasone and disodium cromoglycate of anaphylactic bronchoconstriction in the rat

    PubMed Central

    Church, M. K.; Collier, H. O. J.; James, G. W. L.

    1972-01-01

    1. A method for the measurement of anaphylactic bronchoconstriction in the rat is described. 2. Dexamethasone inhibited this response in a dose-related manner. 3. Disodium cromoglycate antagonized the response. A bell-shaped dose-response curve was obtained with peak activity at 1 mg/kg i.v. 4. Meclofenamate was not active when given alone or in combination with dexamethasone. 5. Methysergide significantly inhibited the response. Mepyramine, atropine, propranolol and adrenalectomy did not significantly modify the response. 6. The relationships of anaphylactic bronchoconstriction in the rat to anaphylactic bronchoconstriction in the guinea-pig and to human asthma are discussed. PMID:4404396

  3. 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.

  4. Effect of amino acids on the dispersion of disodium cromoglycate powders.

    PubMed

    Chew, Nora Y K; Shekunov, Boris Y; Tong, Henry H Y; Chow, Albert H L; Savage, Charles; Wu, James; Chan, Hak-Kim

    2005-10-01

    Modified disodium cromoglycate powders were prepared by co-spray drying with different concentrations of leucine, phenylalanine, tryptophan, methionine, asparagine, and arginine. Amorphous spherical particles of the same size and density where obtained which, however, exhibited different surface properties as measured by the inverse gas chromatography (IGC) and X-ray photoelectron spectroscopy (XPS) techniques. The surface energy parameters, such as the dispersive component of surface free energy of the sample, gammaSD, and the total solubility parameter, delta, were significantly lower in the presence of nonpolar chain amino acids, particularly with leucine and phenylalanine, than pure DSCG. However no quantitative relationship between these parameters, the additive concentrations, and the fine particle fractions, FPF, determined for different inhalers and air flow rates, was observed. The FPF significantly increased with addition of leucine and this effect was attributed to reduced intermolecular interactions between leucine and disodium cromoglycate molecules, as indicated by the difference in corresponding Hansen solubility parameters. Decrease of interparticle interactions for leucine-containing powders also led to a lesser dependence of FPF on the flow rate and inhaler type.

  5. 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 salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate, boric oxide (boric...

  6. 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 salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate, boric oxide (boric...

  7. 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 salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate, boric oxide (boric...

  8. 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 salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate, boric oxide (boric...

  9. 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 salts, borax (sodium borate decahydrate), disodium octaborate tetrahydrate, boric oxide (boric...

  10. Efficacy of didecyl dimethyl ammonium chloride (DDAC), disodium octaborate tetrahydrate (DOT), and chlorothalonil (CTL) against common mold fungi

    Treesearch

    Jessie A. Micales-Glaeser; Jeffrey D. Lloyd; Thomas L. Woods

    2004-01-01

    The fungitoxic properties of four fungicides, alone and in combination, against four different mold fungi commonly associated with indoor air quality problems were evaluated on two different wood species and sheetrock. The fungicides were chlorothalonil (2,4,5,6-tetrachloroisophthalonitrile) (CTL) in a 40.4% aqueous dispersion, disodium octaborate tetrahydrate (DOT) in...

  11. The disodium salt of 2,5-dihydroxy-1,4-benzoquinone as anode material for rechargeable sodium ion batteries.

    PubMed

    Zhu, Zhiqiang; Li, Hao; Liang, Jing; Tao, Zhanliang; Chen, Jun

    2015-01-28

    The disodium salt of 2,5-dihydroxy-1,4-benzoquinone has been prepared and proposed as anode material for rechargeable sodium ion batteries for the first time, showing an average operation voltage of ∼1.2 V, a reversible capacity of ∼265 mA h g(-1), a long cycle life (300 cycles), and high rate capability.

  12. Transient Severe Motion Artifact Related to Gadoxetate Disodium-Enhanced Liver MRI: Frequency and Risk Evaluation at a German Institution.

    PubMed

    Well, Lennart; Rausch, Vanessa Hanna; Adam, Gerhard; Henes, Frank Oliver; Bannas, Peter

    2017-07-01

    Purpose Varying frequencies (5 - 18 %) of contrast-related transient severe motion (TSM) imaging artifacts during gadoxetate disodium-enhanced arterial phase liver MRI have been reported. Since previous reports originated from the United States and Japan, we aimed to determine the frequency of TSM at a German institution and to correlate it with potential risk factors and previously published results. Materials and Methods Two age- and sex-matched groups were retrospectively selected (gadoxetate disodium n = 89; gadobenate dimeglumine n = 89) from dynamic contrast-enhanced MRI examinations in a single center. Respiratory motion-related artifacts in non-enhanced and dynamic phases were assessed independently by two readers blinded to contrast agents on a 4-point scale. Scores of ≥ 3 were considered as severe motion artifacts. Severe motion artifacts in arterial phases were considered as TSM if scores in all other phases were < 3. Potential risk factors for TSM were evaluated via logistic regression analysis. Results For gadoxetate disodium, the mean score for respiratory motion artifacts was significantly higher in the arterial phase (2.2 ± 0.9) compared to all other phases (1.6 ± 0.7) (p < 0.05). The frequency of TSM was significantly higher with gadoxetate disodium (n = 19; 21.1 %) than with gadobenate dimeglumine (n = 1; 1.1 %) (p < 0.001). The frequency of TSM at our institution is similar to some, but not all previously published findings. Logistic regression analysis did not show any significant correlation between TSM and risk factors (all p > 0.05). Conclusion We revealed a high frequency of TSM after injection of gadoxetate disodium at a German institution, substantiating the importance of a diagnosis-limiting phenomenon that so far has only been reported from the United States and Japan. In accordance with previous studies, we did not identify associated risk factors for TSM. Key Points: 

  13. Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration.

    PubMed

    Han, Xiaofeng; Wang, Zhe; Wang, Manyuan; Li, Jing; Xu, Yongsong; He, Rui; Guan, Hongyu; Yue, Zhujun; Gong, Muxin

    2016-06-01

    In order to enhance oral bioavailability and liver targeting delivery of silybin, two amphiphilic hyaluronic acid derivatives, hyaluronic acid-deoxycholic acid (HA-adh-DOCA) and hyaluronic acid-glycyrrhetinic acid (HA-adh-GA) conjugates, were designed and synthesized. Silybin was successfully loaded in HA-adh-DOCA and HA-adh-GA micelles with high drug-loading capacities (20.3% ± 0.5% and 20.6% ± 0.6%, respectively). The silybin-loaded micelles were spherical in shape with the average size around 130 nm. In vitro release study showed that two silybin-loaded micelles displayed similar steady continued-release pattern in simulated gastrointestinal fluids and PBS. Single-pass intestinal perfusion studies indicated that silybin-loaded micelles were absorbed in the whole intestine and transported via a passive diffusion mechanism. Compared with suspension formulation, silybin-loaded HA-adh-DOCA and HA-adh-GA micelles achieved significantly higher AUC and Cmax level. Moreover, liver targeting drug delivery of micelles was confirmed by in vivo imaging analysis. In comparison between the two micellar formulations, HA-adh-GA micelles possessed higher targeting capacity than HA-adh-DOCA micelles, owing to the active hepatic targeting properties of glycyrrhetinic acid. In the treatment of acute liver injury induced by CCl4, silybin-loaded HA-adh-GA micelles displayed better effects over suspension control and silybin-loaded HA-adh-DOCA micelles. Overall, pharmaceutical and pharmacological indicators suggested that the HA-adh-GA conjugates can be successfully utilized for liver targeting of orally administered therapeutics.

  14. Gadoxate disodium: gadolinium EOB DTPA, gadoxetic acid, Gd-EOB-DTPA.

    PubMed

    2004-01-01

    Gadoxate disodium [gadolinium EOB DTPA, Gd-EOB-DTPA, gadoxetic acid, Eovist injection, Primovist] is a hydrophilic paramagnetic contrast agent being developed by Schering AG for hepatobiliary magnetic resonance imaging. In April 2004, gadoxate disodium (Primovist) was approved in Sweden, the reference member state for the EU registration. Following the Swedish approval, Schering will initiate a mutual recognition procedure for the EU with approvals expected in most countries during 2004. Gadoxate disodium is in phase III clinical trials in the US and has completed phase III studies in Japan. Submissions for approval in Japan and other Asian countries are planned for 2004. Schering AG plans to launch Eovist in Japan in 2005. Schering AG acquired a worldwide, royalty-bearing licence to EPIX Medical's patents covering liver-enhancing agents such as Eovist injection. These included a European patent (222886) and the US patents (4,899,755 and 4,888,008) that EPIX Medical exclusively licensed from the Massachusetts General Hospital (MGH). The MGH patents, a part of EPIX's extensive intellectual property, also covered albumin-targeted agents such as MS 325 (AngioMARK). Schering AG formally withdrew from the opposition proceedings against EPIX's EU patent 222886 following its acquisition of EPIX's intellectual property. These EU and US patents were also non-exclusively licensed by EPIX Medical to Bracco in September 2001. Apart from covering Eovist (Schering AG), the EU patent also covered gadobenate dimeglumine (MultiHance Bracco). Following the licensing agreement, Bracco withdrew its opposition to the patents in Europe and Japan, and both EPIX Medical and Bracco settled their European patent dispute. In its 2002 Annual Report, Schering predicted that Eovist has the potential to reach peak sales of euro50 million, three years after launch--at the time, launch in Europe was anticipated in 2004, followed by launch in Japan in 2005. This is down from earlier predictions

  15. The inhibitory effect of disodium cromoglycate on the growth of Chlamydophila (Chlamydia) pneumoniae in vitro.

    PubMed

    Yamazaki, Tsutomu; Yamaguchi, Tetsuya; Sasaki, Nozomu; Inoue, Miyuki; Sato, Kozue; Kishimoto, Toshio

    2006-04-01

    Chlamydophila (Chlamydia) pneumoniae is associated with asthma and several other respiratory illnesses. Disodium cromoglycate (DSCG) is known to inhibit both immediate and late asthmatic responses. In this study, the inhibitory effect of DSCG on the growth of C. pneumoniae was examined by minimum inhibitory concentration (MIC) and pre-inoculation minimal cidal concentration (MCC) assays using HL cells and C. pneumoniae AR-39. DSCG below the clinically relevant concentration inhibited the growth of C. pneumoniae in a dose-dependent manner in both the MCC and MIC assays. The inhibitory effect was also time-dependent in the MCC assay at 20 mg/ml of DSCG. These results warrant further clinical study on the connection between C. pneumoniae infections and use of DSCG.

  16. [Study on the effect of disodium cromoglycate (DSCG) on antigen induced IL-2 responsiveness].

    PubMed

    Ichikawa, K; Baba, M; Yoshizawa, I; Noma, T

    1989-10-01

    We tested the effects of disodium cromoglycate (DSCG) on antigen-induced IL-2 responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma. Patient lymphocytes pretreated with 5 x 10(3) micrograms/ml DSCG for 24 or 48 hours failed to induce the responsiveness to IL-2 on stimulation with Dermatophagoides farinae (Df) or ovalbumin (OVA) antigen. DSCG-treated adherent cells were blocked to present the antigen to nonadherent responding cells for induction of IL-2 responsiveness. In contrast, DSCG-treated non-adherent cells, recombined with antigen-activated adherent cells, acquired IL-2 responsiveness. However, Con A-activated lymphocytes from the same patients were not affected by the same treatment. The results indicate that DSCG is capable of suppressing antigen-induced IL-2 responsiveness but not the response induced by mitogen such as Con A.

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

    PubMed

    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.

  18. Effect of disodium cromoglycate on mast cell-mediated immediate-type allergic reactions.

    PubMed

    Shin, Hye-Young; Kim, Jung-Sook; An, Nyeon-Hyoung; Park, Rae-Kil; Kim, Hyung-Min

    2004-04-23

    We investigated the effect of disodium cromoglycate (DSCG) on mast cell-mediated immediate-type hypersensitivity. DSCG inhibited systemic allergic reaction induced by compound 48/80 dose-dependently. Passive cutaneous anaphylaxis was inhibited by 71.6% by oral administration of DSCG (1 g/kg). When DSCG was pretreated at concentration rang from 0.01-1000 g/kg, the serum histamine levels were reduced in a dose dependent manner. DSCG also significantly inhibited histamine release from rat peritoneal mast cell (RPMC) by compound 48/80. We confirmed that DSCG inhibited compound 48/80-induced degranulation of RPMC by alcian blue/nuclear fast red staining. In addition, DSCG showed a significant inhibitory effect on anti-dinitrophenyl IgE-mediated tumor necrosis factor-alpha production. These results indicate that DSCG inhibits mast cell-mediated immediate-type allergic reaction.

  19. In vitro inhibitory effects of disodium cromoglycate on ionic transports involved in sickle cell dehydration.

    PubMed

    Bizumukama, Léonidas; Ferster, Alina; Gulbis, Béatrice; Kumps, Alain; Cotton, Frédéric

    2009-01-01

    The antiallergic and antiasthmatic drug disodium cromoglycate (DSCG) has also demonstrated an activity against sickle cell disease, but the mechanism of this action still remains unknown. Na(+) and K(+) fluxes were studied in red cells obtained from 9 patients affected with sickle cell disease in the absence or in the presence of 1 mM of DSCG and deoxygenated under an N(2) flow during up to 24 h. A significant inhibiting effect of DSCG on the intracellular K(+) exit and the Na(+) entry was observed. These results demonstrate that DSCG partially inhibits the abnormal K(+) loss which is implicated in the dehydration of the sickle cell and the stimulation of sickling. Copyright 2009 S. Karger AG, Basel.

  20. 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.

  1. Unexpected outcome after two consecutive infusions of disodium EDTA in dairy cows.

    PubMed

    Liesegang, A; Riond, J L; Wanner, M

    1999-04-01

    Disodium ethylenediaminetetraacetic acid (Na2EDTA) is a cation chelator which is used as an anticoagulant in blood samples and as a therapeutic agent in lead poisoning. Several experiments have been carried out with EDTA to induce hypocalcemia in cows and other animals, and toxic effects have rarely been reported. In this study, hypocalcemia was induced by means of a 5% Na2EDTA infusion (0.55 mg/kg/min Na2EDTA for 5 h = total dose of 100.6 g). Accidental acute toxicity and fatalities occurred after a consecutive second infusion in several cows. Researchers designing new experiments should be aware of a potential EDTA toxicity at a routinely used dose and rate of administration.

  2. Metal excretion and magnesium retention in patients with intermittent claudication treated with intravenous disodium EDTA.

    PubMed

    Guldager, B; Jørgensen, P J; Grandjean, P

    1996-12-01

    Sixty patients with intermittent claudication participated in a double-blind placebo-controlled trial of 20 courses of intravenous chelation therapy with 3 g of disodium EDTA vs placebo during 5-9 weeks. After the first infusion, the 24-h urinary excretion of lead and zinc was approximately 25-fold higher in the EDTA-treated group; relative differences for copper and calcium were smaller. Urinary magnesium excretion in the EDTA-treated group was one-third less than in the control group. After the treatment period, the blood lead concentration had decreased by approximately 73% and the serum zinc concentration by approximately 34%; other changes in blood concentrations were negligible. The loss of essential minerals and the possible redistribution of lead in the body may constitute a disadvantage that should be taken into account in repeated intravenous EDTA treatment.

  3. Graphene oxide wrapped croconic acid disodium salt for sodium ion battery electrodes

    NASA Astrophysics Data System (ADS)

    Luo, Chao; Zhu, Yujie; Xu, Yunhua; Liu, Yihang; Gao, Tao; Wang, Jing; Wang, Chunsheng

    2014-03-01

    Croconic acid disodium salt (CADS), a renewable or recyclable organic compound, is investigated as an anode material in sodium ion battery for the first time. The pristine micro-sized CADS delivers a high capacity of 246.7 mAh g-1, but it suffers from fast capacity decay during charge/discharge cycles. The detailed investigation reveals that the severe capacity loss is mainly attributed to the pulverization of CADS particles induced by the large volume change during sodiation/desodiation rather than the generally believed dissolution of CADS in the organic electrolyte. Minimizing the particle size can effectively suppress the pulverization, thus improving the cycling stability. Wrapping CADS with graphene oxide by ultrasonic spray pyrolysis can enhance the integration and conductivity of CADS electrodes, thus providing a high capacity of 293 mAh g-1.

  4. Chiral amplification of disodium cromoglycate chromonics induced by a codeine derivative.

    PubMed

    Berride, F; Troche-Pesqueira, E; Feio, G; Cabrita, E J; Sierra, T; Navarro-Vázquez, A; Cid, M M

    2017-08-18

    Chromonic liquid crystals (CLC) are lyotropic phases formed by discotic mesogens in water. Simple chiral dopants such as amino acids have been reported to turn chromonic liquid crystals into their cholesteric counterparts. Here we report a chirality amplification effect in the nematic phase of a 9 wt% disodium cromoglycate (DSCG) lyotropic liquid crystal (LLC) upon doping with a water-soluble codeine derivative. The transition on cooling the isotropic to the nematic phase showed the presence of homochiral spindle-shaped droplets (tactoids). NMR DOSY experiments on a triple gradient probe revealed a small degree of diffusion anisotropy for the alkaloid embedded in the liquid crystal structure. These results in combination with XRD, CD and POM experiments agree with a supramolecular aggregation model based on simple columnar stacks.

  5. Acute intravenous infusion of disodium dihydrogen (1-hydroxyethylidene)diphosphonate: mechanism of toxicity.

    PubMed

    Francis, M D; Slough, C L

    1984-08-01

    The acute intravenous toxicity of disodium dihydrogen (1-hydroxyethylidene)diphosphonate (etidronate disodium; I) and the mechanism of this toxic response have been investigated in 40 beagle dogs. The intravenous toxicity of I is dependent on the total dose administered and the length of the infusion interval. The toxicity of I is directly related to the ability of the drug to bind or complex with the circulating calcium in the blood. Maximum depressions in ionized calcium coincide in time with peak blood levels of I, and at lethal doses electrocardiographic changes indicative of hypocalcemia are observed. For a 2-min infusion of 2 mg of I/kg, no effect is observed on ionized calcium levels, and the electrocardiogram remains normal. At doses of 16 and 32 mg/kg, coincident with an immediate fall in ionized calcium levels, there is a transient rise in total calcium and a fall in phosphorus levels. The ionized calcium level rises, and total calcium level falls and stabilizes at baseline levels within 30 min after the infusion. However, the phosphorus level rises and exceeds the baseline value, reaching 3-4 times normal by 72 h after the infusion. With proven lethal doses of I (60 mg/kg infused over 2 min) and the simultaneous infusion of an ionized calcium salt such as calcium gluconate (20 mg of Ca2+/kg), electrocardiograms remain normal and death is prevented. Thus, an effective antidote in the event of an overdose or too rapid an infusion of I can be employed to prevent acute toxic effects.

  6. 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.

  7. Efficacy and Safety of Zoledronic Acid and Pamidronate Disodium in the Treatment of Malignant Skeletal Metastasis: A Meta-Analysis.

    PubMed

    Yang, Liqing; Du, Shuai

    2015-10-01

    Solid tumors frequently metastasize to bone. Two bisphosphonates have been investigated for bone metastases including pamidronate disodium and zoledronic acid.By searching the PubMed, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases, we conducted a meta-analysis to determine the efficacy and safety of zoledronic acid compared with pamidronate disodium in reducing pain in patients with bone metastases.Studies were pooled, and the relative risk (RR) and its corresponding 95 % confidence interval (CI) were calculated. Version 12.0 STATA software was used for statistical analysis. Twenty relevant articles were included for this meta-analysis study.The complete response rate in cancer patients treatment with zoledronic acid was significantly higher than that with pamidronate disodium (relative risk [RR] = 1.32 [95% confidence interval (CI), 1.00-1.75]; P = 0.987, I = 0%). However, there was no significant difference in the rate of partial response rate (RR = 1.04, 95% CI: 0.90-1.20; P = 0.942, I = 0%) and in the total effective rate (RR = 1.06, 95% CI: 1.00-1.12; P = 0.998, I = 0%). For adverse events (AE), the incidence of headache in cancer patients with zoledronic acid was significantly lower than that with pamidronate disodium (RR = 0.82, 95% CI: 0.70-0.96; P = 0.793, I = 0%). There was no significant difference in nausea or vomiting (RR = 1.00, 95% CI: 0.92-1.09; P = 0.494, I = 0%), fever (RR = 0.98, 95% CI: 0.85-1.14; P =0.633, I = 0%), fatigue (RR = 1.01, 95% CI: 0.91-1.11; P = 0.914, I = 0%) and anorexia (RR = 1.31, 95% CI: 0.91-1.87; P = 0.024, I = 64.4%).In conclusion, this meta-analysis indicates that treatment with zoledronic acid was more effective than pamidronate disodium in the complete response assessments and the incidence of headache, an AE, was significantly lower in cancer patients with zoledronic acid.

  8. Characterization of the interaction of glycyrrhizin and glycyrrhetinic acid with bovine serum albumin by spectrophotometric-gradient flow injection titration technique and molecular modeling simulations.

    PubMed

    Manouchehri, Firouzeh; Izadmanesh, Yahya; Ghasemi, Jahan B

    2017-09-01

    In this research, the interactions of glycyrrhizin (GL) and glycyrrhetinic acid (GA) with bovine serum albumin (BSA) have been investigated by the novel method of spectrophotometric- gradient flow injection titration technique. The hard-modeling multivariate approach to binding was used for calculation of binding constants and estimation of concentration-spectral profiles of equilibrium species. The stoichiometric ratio of binding was estimated using eigenvalue analysis. Results showed that GL and GA bind BSA with overall binding constants of KGL-BSA=3.85 (±0.09)×10(4)Lmol(-1), KGA-BSA=3.08 (±0.08)×10(4)Lmol(-1). Ligand-BSA complexes were further analyzed by combined docking and molecular dynamics (MD) simulations. Docking simulations were performed to obtain a first guess on the binding structure of the GL/GA-BSA complex, and subsequently analyzed by 20 ns MD simulations in order to evaluate interactions of GL/GA with BSA in detail. Results of MD simulations indicated that GL-BSA complex forms mainly on the basis of hydrogen bonds, while, GA-BSA complex forms on the basis of hydrophobic interactions. Also, water molecules can bridge between the ligand and protein by hydrogen bonds, which are stable during the entire simulation and play an important role in stabilization of the GL/GA-BSA complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 18β-glycyrrhetinic acid suppresses gastric cancer by activation of miR-149-3p-Wnt-1 signaling

    PubMed Central

    Cao, Donghui; Jia, Zhifang; You, Lili; Wu, Yanhua; Hou, Zhen; Suo, Yueer; Zhang, Houjun; Wen, Simin; Tsukamoto, Tetsuya; Oshima, Masanobu; Jiang, Jing; Cao, Xueyuan

    2016-01-01

    18β-glycyrrhetinic acid (GRA) exerts anti-tumor effects on various types of cancer. In the present study, we found that GRA attenuated the severity of gastritis and suppressed gastric tumorigenesis in transgenic mice. We also discovered that miR-149-3p was downregulated in gastric cancer tissues and cell lines as compared to normal gastric tissues and epithelial cells, but was upregulated by GRA. miR-149-3p expression also correlated negatively with lymphnode metastasis. Our functional assays showed that miR-149-3p overexpression inhibited cell proliferation and cell cycle progression while inducing apoptosis, while inhibition of miR-149-3p had the opposite effects. In addition, we identified Wnt-1 as a direct target of miR-149-3p. These data suggest that GRA inhibits the initiation and progression of gastric tumors by ameliorating the inflammatory microenvironment through downregulation of COX-2 expression and by inhibiting Wnt-1 expression through the upregulation of tumor suppressor miR-149-3p. GRA may thus have the potential to serve as a useful therapeutic agent for the prevention and treatment of gastric cancer. PMID:27713126

  10. 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

    2016-07-01

    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.

  11. Effect of reproterol either alone or combined with disodium cromoglycate on airway responsiveness to methacholine.

    PubMed

    Kanniess, Frank; Jörres, Rudolf A; Magnussen, Helgo

    2005-01-01

    Regular use of inhaled beta2-agonists might lead to tolerance as reflected in a loss of bronchoprotection. In vitro-data suggest that this might be prevented by disodium cromoglycate (DSCG). Therefore, we studied the effect of the beta2-agonist reproterol in combination with DSCG. In a cross-over design, 19 subjects with airway hyperresponsiveness inhaled either placebo, 1mg reproterol, 2 mg DSCG, or 1mg reproterol plus 2 mg DSCG 4x daily over 2 weeks. Treatment periods were separated by > or = 7 days. Before and at the end of periods, lung function and methacholine responsiveness were determined in the morning, and 6h later the bronchodilator effect and the protection against methacholine-induced bronchoconstriction. Reproterol or DSCG or their combination did not exert detrimental effects on lung function, airway responsiveness, or bronchodilator capacity. However, bronchoprotection was significantly reduced (p < 0.05) after treatment with placebo, reproterol or reproterol plus DSCG, the respective changes being 0.59, 0.96 and 1.37 doubling concentrations. All changes were small as compared to intraindividual variability. In this model all treatments except with DSCG caused a significant but small loss of protection against methacholine-induced bronchoconstriction. Thus, tolerance was not prevented by 2 weeks of additional treatment with DSCG, in contrast to in vitro findings.

  12. Effects of disodium cromoglycate (DSCG) on the guinea pig trachea and ileum.

    PubMed

    González Alvarez, R; Arruzazabala, M L

    1983-01-01

    Disodium cromoglycate (DSCG) (10(-2)M) significantly inhibits contractions induced by potassium chloride and barium chloride on guinea pig ileum and trachea. The effects of DSCG against these spasmogens are greater on the guinea pig ileum than on its trachea, which may be related with the calcium ion if we take into account that the contraction of the latter preparation seems to be less dependent on the extracellular calcium concentration than the first one. DSCG (10(-2)M) inhibits contractions induced by electrical stimulation (0.1 Hz) but the action of exogenous acetylcholine is not affected. This effect supports a neural site of action for DSCG in the ileum. DSCG (10(-2)M) also suppresses contractions induced by electrical stimulation (20 Hz) on isolated guinea pig trachea. This effect of DSCG is concentration and time dependent. The fact that DSCG inhibits contractions induced by electrical stimulation in both, guinea pig ileum and trachea as well as atropine does, constitute evidence that either an inhibition of acetylcholine release from postganglionic parasympathetic fibers or an anticholinergic effect is involved in the mode of action of DSCG. These effects can be ascribed to membrane stabilizing properties of this antiallergic drug.

  13. Disodium cromoglycate suppresses the induction of cysteinyl leukotriene synthesis during granulocytic differentiation in HL-60 cells.

    PubMed

    Zaitsu, Masafumi; Honjo, Kinji; Ishii, Eiichi; Hamasaki, Yuhei

    2004-03-01

    Disodium cromoglycate (DSCG) and nedocromil sodium are anti-asthma drugs that have a variety of physiological and biological effects. We examined whether DSCG affects the induction of cysteinyl Leukotriene (cysLT) synthesis during dimethyl sulfoxide (DMSO)-induced granulocytic differentiation in HL-60 cells. HL-60 cells were differentiated to mature granulocyte-like cells by DMSO in the presence or absence of DSCG for 5 days. Then, we measured A23187-stimulated production of LTC4, an initial product of cysLTs. We also examined the mRNA expression and enzyme activity of LTC4 synthase and other LT-synthetic enzymes. The amount of LTC4 production was 732.0+/-19.0 pg/10(6) cells in DMSO-differentiated HL-60 cells. The value was significantly decreased to 420.7+/-22.7 pg/10(6) cells in the presence of DSCG at 100 microg/ml. The DMSO-induced mRNA expression and enzyme activity of LTC4 synthase was also suppressed by DSCG. Our results indicate that DSCG suppresses the DMSO-induced LTC4 synthase-activity by inhibiting mRNA expression of LTC4 synthase, which might be a novel anti-allergic action of DSCG.

  14. Disodium cromoglycate in the treatment of ulcerative colitis and Crohn's disease.

    PubMed Central

    Binder, V; Elsborg, L; Greibe, J; Hendriksen, C; Høj, L; Jensen, K B; Kristensen, E; Madsen, J R; Marner, B; Riis, P; Willumsen, L

    1981-01-01

    A controlled clinical study on disodium cromoglycate (DSCG) at a dose of 800 mg per day versus placebo was carried out in 141 patients with ulcerative colitis and 25 patients with Crohn's disease. Those of the ulcerative colitis patients who had been on sulphasalazine treatment continued that treatment during the trial (101 patients). Forty patients were intolerant of sulphasalazine. No patient received steroids during the last month before the study. Patients with Crohn's disease had their possible sulphasalazine treatment stopped before the trial. No beneficial effect of DSCG as compared with placebo was found, as the DSCG and the placebo group showed the same number of relapses in patients with a clinically inactive ulcerative colitis at the start of the trial and the same number of patients improving, deteriorating, and maintaining steady state in patients with clinically active ulcerative colitis at the start of the trial. There was no difference between relapse rate in DSCG and placebo groups in patients with Crohn's disease. No correlation between the eosinophil count in rectal mucosa and the outcome of the attack of ulcerative colitis could be demonstrated. PMID:6780414

  15. Disodium cromoglycate inhibits capsaicin-induced eosinophil infiltration of conjunctiva independent of mast cells.

    PubMed

    Ebihara, Nobuyuki; Nishikawa, Motoaki; Murakami, Akira

    2006-01-01

    To investigate whether disodium cromoglycate (DSCG) inhibits capsaicin-induced eosinophil infiltration of the conjunctiva independent of mast cells. We administered 5 microl of capsaicin solution (10(-5) M) into the conjunctival sacs of mast cell-deficient W/W(v) mice (12 animals) and wild-type mice (12 animals). As controls, the eyes of 12 wild-type and 12 W/W(v) mice were treated with phosphate-buffered saline. Following treatment, the eyelids and eyeballs were removed en bloc at 3, 9, or 24 h, and were histologically examined. The number of infiltrated eosinophils and the expression of vascular cell adhesion molecule-l (VCAM-1) in the conjunctiva were quantified by the staining method of Hansel and immunohistochemical analysis. We also investigated whether treatment by depletion of neuropeptides or by DSCG administration could suppress the capsaicin-induced eosinophil infiltration of the conjunctiva. In both W/W(v) and wild-type mice, eosinophil infiltration of conjunctival tissues was observed 3 h after capsaicin administration. In both strains of mice, the number of infiltrated eosinophils increased over time, with VCAM-1 expression on vascular endothelial cells peaking at 9 h after treatment, and decreasing gradually within 24 h after treatment. In both the neuropeptide-depleted and the DSCG-treated groups, eosinophil infiltration and VCAM-1 expression were suppressed in comparison with the nontreated group. DSCG can directly inhibit neuropeptide-induced eosinophil infiltration of the conjunctiva independent of mast cells.

  16. Effectiveness of budesonide nebulising suspension compared to disodium cromoglycate in early childhood asthma.

    PubMed

    Zielen, S; Rose, M A; Bez, C; Jarisch, A; Reichenbach, J; Hofmann, D

    2006-02-01

    The optimal treatment for early childhood asthma remains controversial. Budesonide (BUD) has shown superiority over placebo in infants, and over disodium cromoglycate (DSCG) in children aged > 2 years. The aim of this double-blind, randomised, parallel-group study was to compare the effectiveness of nebulised BUD and DSCG in asthmatic children aged < 36 months. 82 infants (mean age 18.0 months [range, 11.6-31.2 months]) with suspected asthma (three exacerbations of dyspnoea and wheezing during the past 12 months, with one or more exacerbations in the past 3 months) were treated for 3 months with nebulised BUD (Pulmicort Respules) 0.5 mg/2 mL bid or DSCG 20 mg/2 mL tid. Follow-up was at 6 months. Patients treated with BUD had a lower exacerbation rate than DSCG-treated patients after 3 months of treatment (5.4% vs. 31.7%; p = 0.003) and towards the end of follow-up (30% vs. 49%; p = 0.062). During treatment, days without cough were 80% and 65% for BUD and DSCG, respectively (p = 0.014), and nights without cough were 89% and 78%, respectively (p = 0.016). Side-effects were mild and of similar frequency in both groups. Inhaled nebulised BUD was well tolerated and more effective than nebulised DSCG in reducing the incidence of asthma exacerbations and days with symptoms. These beneficial effects of BUD were maintained throughout the 6-month follow-up.

  17. 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.

  18. In vitro and in vivo inhibitory effects of disodium cromoglycate on influenza virus infection.

    PubMed

    Hidari, Kazuya I P J; Tsujii, Eisaku; Hiroi, Jun; Mano, Eriko; Miyatake, Akihiko; Miyamoto, Daisei; Suzuki, Takashi; Suzuki, Yasuo

    2004-06-01

    Disodium cromoglycate (DSCG) is one of the safest drugs for the prevention of bronchial asthma and allergic rhinitis attacks. The effect of DSCG on acute upper respiratory tract viral infection is still controversial. Here we investigated DSCG inhibition of influenza virus infection in vivo and in vitro. In vivo effects of DSCG on viral infection were assessed using a murine model of respiratory tract infection. Intranasal administration of DSCG protected mice from death induced by infection with influenza virus A/PR/8/34. We analyzed DSCG anti-viral effects in vitro by either (i) treating cells prior to viral adsorption, (ii) treating cells concurrently with viral adsorption, or (iii) treating cells after viral adsorption. DSCG treatment of cells during or after, but not before, viral adsorption significantly inhibited influenza viral infection, indicating DSCG acts on events late in viral infection. DSCG exerts anti-influenza effect both in vitro and in vivo at the doses compatible with treatment for asthma. DSCG marginally inhibited influenza viral neuraminidase and membrane fusion functions, suggesting that DSCG inhibition of viral neuraminidase and fusion activities may partially mediate this anti-influenza effect. Our results indicate that treatment of patients including children with DSCG may take advantages for prevention from influenza virus infection.

  19. The new role of disodium cromoglycate in the treatment of adults with bronchial asthma.

    PubMed

    Miyatake, Akihiko; Fujita, Mari; Nagasaka, Yukio; Fujita, Kimie; Tamari, Mayumi; Watanabe, Dai; Nakano, Naoko; Hidari, Kazuya I P J; Suzuki, Yasuo

    2007-09-01

    Viral infection of the respiratory tract in patients with asthma is one of the most frequent causes of exacerbation of asthmatic symptoms. Disodium cromoglycate (DSCG) is a commonly used anti-asthmatic medicine with many beneficial biochemical and physiological effects. The purpose of this study was to investigate the efficacy of DSCG against colds when used in clinical practice. A questionnaire survey to determine the efficacy of DSCG was undertaken in 220 adult patients with asthma (81 male, 139 female; mean age: 54.1 +/- 13.7 years and 60.1 +/- 12.7 years, respectively) from April to September 2004 at the Miyatake Asthma Clinic. The duration of DSCG inhalation therapy was not less than 5 years in more than half of the patients. The mean daily DSCG dose at the time of the questionnaire survey was 40mg/day in over 50% of all patients. After DSCG was added to inhaled corticosteroid (ICS) combination therapy, 56.4% of the patients rated their condition as "improved", and 66.4% of the patients felt that the frequency of colds they had caught had decreased while DSCG was added to ICS. DSCG inhalation therapy is a useful additional treatment following ICS to alleviate asthma symptoms, and to prevent colds in adult patients with asthma.

  20. Disodium cromoglycate attenuates hypoxia induced enlargement of end-expiratory lung volume in rats.

    PubMed

    Maxová, H; Hezinová, A; Vízek, M

    2011-01-01

    Mechanism responsible for the enlargement of end-expiratory lung volume (EELV) induced by chronic hypoxia remains unclear. The fact that the increase in EELV persists after return to normoxia suggests involvement of morphological changes. Because hypoxia has been also shown to activate lung mast cells, we speculated that they could play in the mechanism increasing EELV similar role as in vessel remodeling in hypoxic pulmonary hypertension (HPH). We, therefore, tested an effect of mast cells degranulation blocker disodium cromoglycate (DSCG) on hypoxia induced EELV enlargement. Ventilatory parameters, EELV and right to left heart weight ratio (RV/LV+S) were measured in male Wistar rats. The experimental group (H+DSCG) was exposed to 3 weeks of normobaric hypoxia and treated with DSCG during the first four days of hypoxia, control group was exposed to hypoxia only (H), two others were kept in normoxia as non-treated (N) and treated (N+DSCG) groups. DSCG treatment significantly attenuated the EELV enlargement (H+DSCG = 6.1+/-0.8; H = 9.2+/-0.9; ml +/-SE) together with the increase in minute ventilation (H + DSCG = 190+/-8; H = 273 +/- 10; ml/min +/- SE) and RV/LV + S (H + DSCG = 0.39 +/- 0.03; H = 0.50 +/- 0.06).

  1. Plasma concentrations of disodium cromoglycate after various inhalation methods in healthy subjects

    PubMed Central

    Kato, Y; Muraki, K; Fujitaka, M; Sakura, N; Ueda, K

    1999-01-01

    Aims To compare the plasma concentrations of disodium cromoglycate (DSCG) following various inhalation procedures in healthy volunteers. Methods Nine healthy subjects inhaled 2 mg of aerosol, 20 mg of nebuliser solution only, 20 mg of nebuliser solution mixed with isotonic saline, or 20 mg of nebuliser solution mixed with saline and procaterol, a β2-adenoceptor agonist, on separate occasions 2–3 weeks apart. Plasma concentrations of DSCG were determined by high-performance liquid chromatography (h.p.l.c.). Results The peak plasma concentrations of DSCG were 1.5±0.7 (range 0.4–2.4) ng ml−1 in the aerosol group, 8.8±6.2 (range 5.3–19.9) ng ml−1 in the nebuliser solution only group, 17.2±16.3 (range 5.0–38.6) ng ml−1 in the nebuliser solution plus isotonic saline group, and 24.5±11.9 (range 10.2–44.9) ng ml−1 in the nebuliser solution plus saline and procaterol group. Thus subjects who used the nebuliser had markedly higher plasma concentrations of DSCG than subjects who used the aerosol inhaler. Conclusions These findings may have important implications for the evaluation of inhalation treatment with DSCG for bronchial asthma. PMID:10417491

  2. Have inadequate delivery systems hampered the clinical success of inhaled disodium cromoglycate? Time for reconsideration.

    PubMed

    Keller, Manfred; Schierholz, Joerg

    2011-01-01

    Disodium cromoglycate (DSCG) fits with the perception of a safe drug, but conclusions from questionable meta-analyses reduced its use. In addition, drug delivery aspects, such as hygroscopicity and the poor performance of delivery systems, were not considered to be important determinants of therapeutic failures. Drug delivery aspects and parameters affecting lung deposition and distribution, important parameters for therapeutic efficacy, are addressed. In addition, the distribution and ratio of mast cell tryptase and chymase-positive phenotypes in the lungs and their role in the prostaglandin and leukotriene pathway are discussed. Information on why in vitro data are an excellent tool to understand better therapeutic failures associated with the moisture sensitivity of DSCG and the difficulty in handling and operating DSCG delivery systems in a therapeutically reliable way. Pharmacological efficacy of DSCG has been demonstrated in animals and humans. If the drug is delivered to the site of inflammation in an effective dose, a reliable therapeutic effect can be expected. DSCG has extra properties and potential unspecific antiviral properties and may offer new therapeutic treatment aspects for asthma and viral-induced bronchiolitis in early childhood.

  3. Disodium cromoglycate inhibits asthma-like features induced by sphingosine-1-phosphate.

    PubMed

    Roviezzo, Fiorentina; Sorrentino, Rosalinda; Iacono, Valentina Mattera; Brancaleone, Vincenzo; Terlizzi, Michela; Riemma, Maria Antonietta; Bertolino, Antonio; Rossi, Antonietta; Matteis, Maria; Spaziano, Giuseppe; Pinto, Aldo; D'Agostino, Bruno; Cirino, Giuseppe

    2016-11-01

    Compelling evidence suggests the involvement of sphingosine-1-phosphate (S1P) in the pathogenesis of asthma. The systemic administration of S1P causes asthma like features in the mouse involving mast cells. In this study we investigated whether disodium cromoglycate (DSCG), administered as a preventative treatment as in human therapy, could affect S1P effects on airways. BALB/c mice, treated with DSCG, received subcutaneous administration of S1P. Bronchi and pulmonary tissues were collected and functional, molecular and cellular studies were performed. DSCG inhibited S1P-induced airway hyper-reactivity as well as pulmonary inflammation. DSCG decreased the recruitment of solely mast cells and B cells in the lung. IgE serum levels, prostaglandin D2, mucus production and IL-13 were also reduced when mice were pretreated with DSCG. S1P induced pulmonary expression of CD23 on T and B cells, that was reversed by DSCG. Conversely, S1P failed to upregulate CD23 in mast cell-deficient Kit (W-sh/W-sh) mice. In conclusion we have shown that DSCG inhibits S1P-induced asthma like features in the mouse. This beneficial effect is due to a regulatory action on mast cell activity, and in turn to an inhibition of IgE-dependent T and B cells responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Effect of lodoxamide and disodium cromoglycate on tear eosinophil cationic protein in vernal keratoconjunctivitis

    PubMed Central

    Leonardi, A.; Borghesan, F.; Avarello, A.; Plebani, M.; Secchi, A.

    1997-01-01

    AIM—To validate the use of tear eosinophil cationic protein (ECP) as a marker for eosinophil activation, and its pharmacological modulation, in addition to evaluating the efficacy of lodoxamide and sodium cromoglycate in the treatment of vernal keratoconjunctivitis (VKC).
METHODS—Tears were collected from 30 patients affected by active mild to moderate VKC before and after therapy with disodium cromoglycate 4% (DSCG) (n=15) or lodoxamide 0.1% (n=15) for 10 days. Tear cytology and ECP measurement were performed, and ocular signs and symptoms evaluated.
RESULTS—While statistically significant changes did not occur after DSCG therapy, mean tear ECP increased from 343 (SD 363) µg/l to 571 (777) µg/l due to marked elevation in six eyes. The clinical score in DSCG eyes did not improve. After lodoxamide therapy, both clinical signs and symptoms, and tear ECP levels (560 (756) µg/l to 241 (376) µg/l) decreased significantly (p<0.0001 and p<0.01, respectively). Compared with DSCG treatment, lodoxamide was more effective in reducing signs and symptoms (p<0.005). ECP levels were significantly correlated with signs, symptoms, corneal involvement, and number of eosinophils in tears (p<0.0001).
CONCLUSIONS—In patients with VKC, lodoxamide significantly reduced ECP tear levels, and thus, eosinophil activation, and was more effective than DSCG in reducing clinical signs and symptoms.

 PMID:9135403

  5. Modification of disodium cromoglycate passage across lung epithelium in vitro via incorporation into polymeric microparticles.

    PubMed

    Haghi, Mehra; Salama, Rania; Traini, Daniela; Bebawy, Mary; Young, Paul M

    2012-03-01

    Two microparticle systems containing disodium cromoglycate (DSCG) alone or with polyvinyl alcohol (DSCG/PVA) were produced via spray drying and compared in terms of their physicochemical characteristics, aerosol performance and drug uptake across a pulmonary epithelial cell line (Calu-3), cultured under air interface conditions. The particle size distribution of DSCG and DSCG/PVA were similar, of spherical geometry, amorphous and suitable for inhalation purposes. Aerosolisation studies using a modified twin-stage impinger showed the DSCG/PVA to have greater aerosol performance than that of DSCG alone. Aerosol particles of DSCG and DSCG/PVA were deposited onto the surface of the Calu-3 air interface epithelium monolayer and the drug uptake from apical to basal directions measured over time. Drug uptake was measured across a range of doses to allow comparison of equivalent drug and powder mass deposition. Analysis of the data indicated that the percentage cumulative drug uptake was independent of the mass of powder deposited, but dependent on the formulation. Specifically, with the formulation containing DSCG, the diffusion rate was observed to change with respect to time (indicative of a concentration-dependent diffusion process), whilst DSCG/PVA showed a time-independent drug uptake (suggesting a zero-order depot release).

  6. Calcium disodium edetate enhances type A monoamine oxidase activity in monkey brain.

    PubMed

    Egashira, Toru; Sakai, Kumiko; Sakurai, Mami; Takayama, Fusako

    2003-09-01

    The effects of metal chelators on monoamine oxidase (MAO) isozymes, MAO-A and MAO-B, in monkey brain mitochondria were investigated in vitro. MAO-A activity increased to about 40% with 0.1 microM calcium disodium edetate (CaNa2EDTA) using serotonin as a substrate, and this activation was proportional to the concentration of CaNa2EDTA. On the other hand, MAO-A activities were decreased gradually with an increasing concentration of o-phenanthroline and diethyldithiocarbamic acid, but these metal chelators had no effect on MAO-B activity in monkey brain. The activation of MAO-A activity by CaNa2EDTA was reversible. CaNa2EDTA did not activate both MAO-A and MAO-B activities in rat brain mitochondria. Zn and Fe ions were found in the mitochondria of monkey brain. Zn ions potently inhibited MAO-A activity, but Fe ions did not inhibit either MAO-A or MAO-B activity in monkey brain mitochondria. These results indicate that the activating action of CaNa2EDTA on MAO-A was the result of the chelating of Zn ions contained in mitochondria by CaNa2EDTA. These results also indicate the possibility that Zn ions may regulate physiologically the level of serotonin and norepinephrine content in brain by inhibiting a MAO-A activity.

  7. Edetate calcium disodium nanoparticle dry powder inhalation: a novel approach against heavy metal decorporation.

    PubMed

    Kumar, Neeraj; Soni, Sandeep; Jaimini, Abhinav; Ahmad, Farhan Jalees; Bhatnagar, Aseem; Mittal, Gaurav

    2011-09-15

    Objective was to develop and characterize nano-edetate calcium disodium (Ca-Na(2)EDTA) dry powder inhaler (DPI), and assess its in vitro and in vivo deposition using pharmacoscintigraphy techniques. Factors influencing nanoparticle formation including concentration of drug, polymer solution and stirring rate were determined. Optimized formulation was characterized with the help of SEM, TEM and Malvern Zetasizer studies. Any change in physical characteristics after nanosizing was determined by FT-IR, XRD and DSC studies. Anderson cascade impaction showed that nano Ca-Na(2)EDTA exhibited significantly higher respirable fraction of 67.35±2.27% and 66.40±2.87% by scintigraphic and spectroscopic analysis respectively, as compared to 10.08±1.17% and 9.36±1.02% respectively for micronized form. Ventilation lung scintigraphy done in 12 volunteers showed significant increase in drug delivery till alveolar region with nano Ca-Na(2)EDTA. The developed formulation may have a role in neutralizing heavy metal toxicity through inhalation route, including radio-metal contamination. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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.

  10. Enhanced vasculotoxic metal excretion in post-myocardial infarction patients following a single edetate disodium-based infusion.

    PubMed

    Arenas, Ivan A; Navas-Acien, Ana; Ergui, Ian; Lamas, Gervasio A

    2017-10-01

    Toxic metals have been associated with cardiovascular mortality and morbidity. We have hypothesized that enhanced excretion of vasculotoxic metals might explain the positive results of the Trial to Assess Chelation Therapy (TACT). The purpose of this study was to determine whether a single infusion of the edetate disodium- based infusion used in TACT led to enhanced excretion of toxic metals known to be associated with cardiovascular events. Twenty six patients (post-MI, age > 50 years, serum creatinine ≤ 2.0mg/dL) were enrolled in this open-label study. Urinary levels of 20 toxic metals normalized to urinary creatinine concentrations were measured at baseline in overnight urine collections, for 6h following a placebo infusion of 500mL normal saline and 1.2% dextrose, and for 6h following a 3g edetate disodium-based infusion. Self-reported metal exposure, smoking status, food frequency, occupational history, drinking water source, housing and hobbies were collected at baseline by a metal exposure questionnaire. The mean age was 65 years (range 51-81 years). All patients were male. 50% had diabetes mellitus and 58% were former smokers. Mean (SD) serum creatinine was 0.95 (0.31) mg/dL. Toxic metals were detected in the baseline urine of >80% of patients. After placebo infusion there were no significant changes in total urinary metal levels. After edetate infusion, total urinary metal level increased by 71% compared to baseline (1500 vs. 2580µg/g creatinine; P<0.0001). The effect of edetate was particularly large for lead (3835% increase) and cadmium (633% increase). Edetate disodium-based infusions markedly enhanced the urinary excretion of lead and cadmium, toxic metals with established epidemiologic evidence and mechanisms linking them to coronary and vascular events. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Effects of lodoxamide, disodium cromoglycate and fluorometholone on tear leukotriene levels in vernal keratoconjunctivitis.

    PubMed

    Akman, A; Irkeç, M; Orhan, M

    1998-01-01

    We compared tear leukotriene B4 (LTB4) and leukotriene C4 (LTC4) levels of vernal keratoconjunctivitis (VKC) patients with those of age-matched controls and evaluated the effects of disodium cromoglycate (DCG) 2%, lodoxamide 0.1% and fluorometholone 0.1% on the tear LTB4 and LTC4 levels of the VKC patients. Thirty VKC patients were divided into three groups and their tear LTB4 and LTC4 levels measured with an enzyme-linked immunoassay technique before and after treatment with either lodoxamide 0.1%, DCG 2% or fluorometholone 0.1%. The results were compared with the tear LTB4 and LTC4 levels of 10 healthy control subjects. During this trial period, clinical scores for signs and symptoms of VKC were also evaluated. In the VKC patients median tear LTB4 and LTC4 levels were 349.0 pg/ml (range 213.3-707.7 pg/ml) and 225.2 pg/ml (range 196.1-241.1 pg/ml) respectively--significantly higher than the control group (p = 0.0065 for LTB4 and p = 0.0003 for LTC4). After treatment, LTB4 levels decreased significantly in all treatment groups when compared with baseline (for the lodoxamide group, p = 0.01; for the DCG group, p = 0.008; for the fluorometholone group, p = 0.045). LTC4 levels were also significantly reduced after treatment in all three treatment groups (for the lodoxamide group, p = 0.0209; for the DCG group, p = 0.0284; for the fluorometholone group, p = 0.0109). Tear LTB4 and LTC4 levels are significantly higher in VKC patients than controls, which points to a possible role of lipoxygenase pathway products in the pathophysiology of ocular allergic disorders. Lodoxamide 0.1%, DCG 2% and fluorometholone 0.1% were all effective in reducing LTB4 and LTC4 levels in VKC.

  12. 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

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

    PubMed

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

    2000-11-01

    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. 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. 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 0.13 to 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. 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.

  14. 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.

  15. Hsp90 is a direct target of the anti-allergic drugs disodium cromoglycate and amlexanox.

    PubMed Central

    Okada, Miki; Itoh, Hideaki; Hatakeyama, Takashi; Tokumitsu, Hiroshi; Kobayashi, Ryoji

    2003-01-01

    Hsp90 (heat-shock protein 90) alone can act to prevent protein aggregation and promote refolding in vitro, but in vivo it operates as a part of a multichaperone complex, which includes Hsp70 and cohort proteins. Since the physiological function of Hsp90 is not yet fully understood, the development of specific antagonists might open new lines of investigation on the role of Hsp90. In an effort to discover Hsp90 antagonists, we screened many drugs and found that the anti-allergic drugs DSCG (disodium cromoglycate) and amlexanox target Hsp90. Both drugs were found to bind directly wild-type Hsp90 via the N- and C-terminal domains. Both drugs strongly suppressed the in vitro chaperone activity of native Hsp90 towards citrate synthase at 1.5-3.0 microM. Amlexanox suppressed C-terminal chaperone activity in vitro, but not N-terminal chaperone activity, and inhibited the association of cohort proteins, such as cyclophilin 40 and Hsp-organizing protein, to the C-terminal domain of Hsp90. These data suggest that amlexanox might disrupt the multichaperone complex, including Hsp70 and cohort proteins, both in vitro and in vivo. Although DSCG inhibited the in vitro chaperone activity of the N-terminal domain, the drug had no effect either on the C-terminal chaperone activity or on the association of the cohort proteins with the C-terminus of Hsp90. The physiological significance of these interactions in vivo remains to be investigated further, but undoubtedly must be taken into account when considering the pharmacology of anti-allergic drugs. DSCG and amlexanox may serve as useful tools for evaluating the physiological significance of Hsp90. PMID:12803546

  16. Disodium cromoglycate, a mast-cell stabilizer, alters postradiation regional cerebral blood flow in primates

    SciTech Connect

    Cockerham, L.G.; Doyle, T.F.; Pautler, E.L.; Hampton, J.D.

    1986-01-01

    Early transient incapacitation (ETI) is the complete cessation of performance during the first 30 min after radiation exposure, and performance decrement (PD) is a reduction in performance at the same time. Supralethal doses of radiation have been shown to produce a marked decrease in regional cerebral blood flow in primates concurrent with systemic hypotension and a dramatic release of mast-cell histamine. In an attempt to elucidate mechanisms underlying the radiation-induced ETI/PD phenomena and the postradiation decrease in cerebral blood flow, primates were given the mast-cell stabilizers disodium cromoglycate (DSCG) or BRL 22321 before exposure to 100 Gy whole-body gamma radiation. Hypothalamic and cortical blood flows were measured by hydrogen clearance, before and after radiation exposure. Systemic blood pressures were determined simultaneously. The data indicated that DSCG was successful in diminishing postradiation decrease in cerebral blood flow. Irradiated animals pretreated with DSCG, showed only a 10% decrease in hypothalamic blood flow 60 min postradiation, while untreated, irradiated animals showed a 57% decrease. The cortical blood flow of DSCG treated, irradiated animals showed a triphasic response, with a decrease of 38% at 10 min postradiation, then a rise to 1% below baseline at 20 min, followed by a fall to 42% below baseline by 50 min postradiation. In contrast, the untreated, irradiated animals showed a steady decrease in cortical blood flow to 79% below baseline by 50 min postradiation. There was no significant difference in blood-pressure response between the treated and untreated, irradiated animals. Systemic blood pressure showed a 60% decrease at 10 min postradiation, falling to a 71% decrease by 60 min.

  17. 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

  18. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

    PubMed Central

    Pivot, X; Raymond, E; Laguerre, B; Degardin, M; Cals, L; Armand, J P; Lefebvre, J L; Gedouin, D; Ripoche, V; Kayitalire, L; Niyikiza, C; Johnson, R; Latz, J; Schneider, M

    2001-01-01

    This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusion on day 1 of a 21-day cycle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2.9–20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall survival was 6.4 months (range 0.7–28.1 months; 95% CI: 3.9–7.7 months). 24 patients (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B12 supplementation. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11531245

  19. Lead mobilization during calcium disodium ethylenediaminetetraacetate chelation therapy in treatment of chronic lead poisoning.

    PubMed

    Sánchez-Fructuoso, Ana I; Cano, Montserrat; Arroyo, Miguel; Fernández, Christina; Prats, Dolores; Barrientos, Alberto

    2002-07-01

    It has long been established that chronic lead (Pb) poisoning is a cause of renal insufficiency. However, although easily diagnosed, there is still no treatment available that will revert this type of poisoning. We report a study performed on 56 male Wistar rats administered Pb in drinking water (500 ppm Pb acetate) over a 90-day period. Twenty-one non-Pb-exposed animals served as the control group. Seven animals from each group were killed days 60 and 90. At the end of the 90-day period, 21 of the Pb-exposed animals were treated with disodium monocalcium EDTA (50 mg/kg/d for 5 days) intraperitoneally and 21 animals were administered serum saline by the same route. Three treatment courses were administered, separated by 9 days free of treatment. Seven animals from each subgroup were killed at the end of each treatment course. Pb levels were determined in blood, urine, liver, brain, kidney, and bone. Treatment with EDTA led to a greater and more rapid reduction in Pb contents in the brain and kidney. The decrease in hepatic Pb levels in the treated group of animals was similar to that in the group administered placebo. Bone Pb levels also failed to show a response to the chelating agent. Use of EDTA appears to result in a reduction in Pb deposits in such critical organs as the kidney and brain. However, the chelating agent does not seem to have access to bone Pb deposits, such that the skeleton becomes a permanent source of poisoning for other tissues. Copyright 2002 by the National Kidney Foundation, Inc.

  20. Effect of edetate calcium disodium on yttrium-90 activity in bone of mice.

    PubMed

    Watanabe, N; Oriuchi, N; Tanada, S; Murata, H; Inoue, T; Kim, E E; Sasaki, Y; Endo, K

    1999-12-01

    The kinetics of Yttrium-90 (Y-90) in bone of mice was investigated in combination with edetate calcium disodium (CaNa2EDTA). One group of mice were intraperitoneally administered 37.5 mg/kg CaNa2EDTA or 0.9% NaCl as a control at 1, 22, 34, 46, 58, 70, 82, 94, 154 and 166 h after injection of Y-90 acetate (post-administration), and the biodistribution was studied at 3, 24, 72, 120 and 168 h postinjection of Y-90 acetate. No difference between the post-CaNa2EDTA-treated mice and the control was demonstrated in the radioactivity in the bone. A decrease in radioactivity in the liver and kidneys was accelerated, and the radioactivity was lower than the control at 120 h postinjection. The other group of mice were also given the same dose of chelator at 12 h and 1 h preinjection of Y-90 acetate and at 1, 22, 34, 46, 58, 70, 82, 94, 154 and 166 h after injection of Y-90 acetate (pre- and post-administration), the radioactivity in bone at 3 h postinjection was significantly lower than in the control (24.4 +/- 3.92% ID/g vs. 31.7 +/- 2.26% ID/g, p < 0.05), but the decrease was not sequential. A significant reduction in radioactivity in the blood, kidneys and liver was demonstrated at 3 h, 72 h and 72 h postinjection. In conclusion, the CaNa2EDTA with the administration schedule employed here cannot chelate the Y-90 from bone but the free Y-90 before deposition into bone.

  1. 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.

  2. Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses.

    PubMed

    Zozaya, D H; Gutiérrez, O L; Ocampo, C L; Sumano, L H

    2008-08-01

    Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C(S0)) was 112.21 +/- 1.27 microg/mL and 201.43 +/- 1.56 microg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC(90)) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 +/- 2.26 microg/mL with 10 mg/kg SC and 72.14 +/- 3.04 microg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC(0-12)/MIC(90) ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC(0-12)/MIC(90) ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.

  3. Intravenous Gadoxetate Disodium Administration Reduces Breath-holding Capacity in the Hepatic Arterial Phase: A Multi-Center Randomized Placebo-controlled Trial

    PubMed Central

    McClellan, Taylor R.; Motosugi, Utaroh; Middleton, Michael S.; Allen, Brian C.; Jaffe, Tracy A.; Miller, Chad M.; Reeder, Scott B.; Sirlin, Claude B.; Bashir, Mustafa R.

    2017-01-01

    Purpose To determine, in a multicenter double-blinded placebo-controlled trial, whether maximal hepatic arterial phase breath-holding duration is affected by gadoxetate disodium administration. Materials and Methods Institutional review board approval was obtained for this prospective multi-institutional HIPAA-compliant study; written informed consent was obtained from all subjects. At three sites, a total of 44 volunteers underwent a magnetic resonance (MR) imaging examination in which images were acquired before and dynamically after bolus injection of gadoxetate disodium, normal saline, and gadoterate meglumine, administered in random order in a single session. The technologist and volunteer were blinded to the agent. Arterial phase breath-holding duration was timed after each injection, and volunteers reported subjective symptoms. Heart rate (HR) and oxygen saturation were monitored. Images were independently analyzed for motion artifacts by three radiologists. Arterial phase breath-holding duration and motion artifacts after each agent were compared by using the Mann-Whitney U test and the McNemar test. Factors affecting the above outcomes were assessed by using a univariate, multivariable model. Results Arterial phase breath holds were shorter after gadoxetate disodium (mean, 32 seconds ± 19) than after saline (mean, 40 seconds ± 17; P <.001) or gadoterate meglumine (43 seconds ± 21, P < .001) administration. In 80% (35 of 44) of subjects, arterial phase breath holds were shorter after gadoxetate disodium than after both saline and gadoterate meglumine. Three (7%) of 44 volunteers had severe arterial phase motion artifacts after gadoxetate disodium administration, one (2%; P = .62) had them after gadoterate meglumine administration, and none (P = .25) had them after saline administration. HR and oxygen saturation changes were not significantly associated with contrast agent. Conclusion Maximal hepatic arterial phase breath-holding duration is reduced after

  4. In Silico and In Vivo Anti-Malarial Studies of 18β Glycyrrhetinic Acid from Glycyrrhiza glabra

    PubMed Central

    Kalani, Komal; Agarwal, Jyoti; Alam, Sarfaraz; Khan, Feroz; Pal, Anirban; Srivastava, Santosh Kumar

    2013-01-01

    Malaria is one of the most prevailing fatal diseases causing between 1.2 and 2.7 million deaths all over the world each year. Further, development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents possessing novel modes of action. Over the past few years triterpenoids from higher plants have shown a wide range of anti-malarial activities. As a part of our drug discovery program for anti-malarial agents from Indian medicinal plants, roots of Glycyrrhizaglabra were chemically investigated, which resulted in the isolation and characterization of 18β-glycyrrhetinic acid (GA) as a major constituent. The in vitro studies against P. falciparum showed significant (IC50 1.69µg/ml) anti-malarial potential for GA. Similarly, the molecular docking studies showed adequate docking (LibDock) score of 71.18 for GA and 131.15 for standard anti-malarial drug chloroquine. Further, in silico pharmacokinetic and drug-likeness studies showed that GA possesses drug-like properties. Finally, in vivo evaluation showed a dose dependent anti-malarial activity ranging from 68–100% at doses of 62.5–250mg/kg on day 8. To the best of our knowledge this is the first ever report on the anti-malarial potential of GA. Further work on optimization of the anti-malarial lead is under progress. PMID:24086367

  5. Glycyrrhetinic acid and E.resveratroloside act as potential plant derived compounds against dopamine receptor D3 for Parkinson’s disease: a pharmacoinformatics study

    PubMed Central

    Mirza, Muhammad Usman; Mirza, A Hammad; Ghori, Noor-Ul-Huda; Ferdous, Saba

    2015-01-01

    Parkinson’s disease (PD) is caused by loss in nigrostriatal dopaminergic neurons and is ranked as the second most common neurodegenerative disorder. Dopamine receptor D3 is considered as a potential target in drug development against PD because of its lesser side effects and higher degree of neuro-protection. One of the prominent therapies currently available for PD is the use of dopamine agonists which mimic the natural action of dopamine in the brain and stimulate dopamine receptors directly. Unfortunately, use of these pharmacological therapies such as bromocriptine, apomorphine, and ropinirole provides only temporary relief of the disease symptoms and is frequently linked with insomnia, anxiety, depression, and agitation. Thus, there is a need for an alternative treatment that not only hinders neurodegeneration, but also has few or no side effects. Since the past decade, much attention has been given to exploitation of phytochemicals and their use in alternative medicine research. This is because plants are a cheap, indispensable, and never ending resource of active compounds that are beneficial against various diseases. In the current study, 40 active phytochemicals against PD were selected through literature survey. These ligands were docked with dopamine receptor D3 using AutoDock and AutoDockVina. Binding energies were compared to docking results of drugs approved by the US Food and Drug Administration against PD. The compounds were further analyzed for their absorption, distribution, metabolism, and excretion-toxicity profile. From the study it is concluded that glycyrrhetinic acid and E.resveratroloside are potent compounds having high binding energies which should be considered as potential lead compounds for drug development against PD. PMID:25565772

  6. The effects of 18β-glycyrrhetinic acid and glycyrrhizin on intestinal absorption of paeoniflorin using the everted rat gut sac model.

    PubMed

    He, Rui; Xu, Yongsong; Peng, Jingjing; Ma, Tingting; Li, Jing; Gong, Muxin

    2017-01-01

    Paeoniflorin (PF), the main active component of Shaoyao-Gancao-tang, possesses significantly antinociceptive effects and many other pharmacological activities. However, its poor intestinal absorption results in low bioavailability. Therefore, enhancing PF absorption plays a vital role in exerting its therapeutic effect. Shaoyao combined with Gancao exhibited a synergistic effect. The enhancement of PF absorption through the interaction of its constituents in intestinal absorption would be greatly implicated. The present study aimed at investigating the effects of glycyrrhizin, the main constituent of Gancao, and its main metabolite, 18β-glycyrrhetinic acid (18β-GA), on the intestinal absorptive behavior of PF, and the role of P-glycoprotein (P-gp) in PF absorption using the in vitro everted rat gut sac model. The results demonstrated that 1 mM of 18β-GA significantly increased PF absorption in both the jejunum and the ileum, while 100 μM of 18β-GA only promoted the ileum absorption and had no obvious effect on the jejunum absorption. The effect of glycyrrhizin on intestinal PF absorption was related to concentrations. One mM of glycyrrhizin significantly increased PF absorption in the jejunum after 45 min and in the ileum after 90 min. But 100 μM of glycyrrhizin had an inhibitory effect in the jejunum and no effect in the ileum before 60 min. Moreover, verapamil, the well-known P-gp inhibitor, could significantly enhance the PF absorption. In conclusion, the influence of 18β-GA and glycyrrhizin on the PF absorption was related to concentrations and intestinal segments. This might be involved in the intervention of efflux transport of PF mediated by intestinal P-gp.

  7. Pseudolesion of the liver on gadoxetate disodium-enhanced MR images obtained after transarterial chemoembolization for hepatocellular carcinoma: clinicoradiologic correlation.

    PubMed

    Shinagawa, Yoshinobu; Sakamoto, Keiko; Fujimitsu, Ritsuko; Shimakura, Mikiko; Kora, Shin-ichi; Takano, Koichi; Yoshimitsu, Kengo

    2012-11-01

    The purpose of this study was to elucidate the clinicoradiologic characteristics of pseudolesions of the liver in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) as observed on gadoxetate disodium-enhanced MR images. A particular interest was correlation between the pseudolesion characteristics and TACE-MRI interval, during which sequential changes in pseudolesions may be revealed after TACE. Forty-eight patients with HCC who underwent gadoxetate disodium-enhanced MRI after TACE were retrospectively recruited. Pseudolesions were defined as areas of decreased signal intensity in treated areas on hepatocellular phase images that were confirmed to be nontumorous areas at follow-up. The prevalence and MRI features of pseudolesions were correlated with various clinical parameters, including TACE-MRI interval. Pseudolesions were found in 14 patients (29%). Within 1 month of TACE, the prevalence of pseudolesions was 83%. All of the pseudolesions had arterial enhancement, mimicking residual HCC. After 1 month, the prevalence of pseudolesions decreased, and these pseudolesions tended to exhibit no abnormality in any sequence other than the hepatocellular phase. Results of multivariate analysis suggested that size of HCC (p < 0.0001), duration of postembolization syndrome (p = 0.012), and TACE-MRI interval (p = 0.038) are independent indicators of the presence of pseudolesions. The prevalence and appearance of pseudolesions differ at different intervals from TACE. Radiologists need to recognize the clinicoradiologic characteristics to differentiate pseudolesions from true residual or recurrent HCC.

  8. Inhibitory effect of disodium EDTA upon the growth of Staphylococcus epidermidis in vitro: relation to infection prophylaxis of Hickman catheters.

    PubMed Central

    Root, J L; McIntyre, O R; Jacobs, N J; Daghlian, C P

    1988-01-01

    Granulocytopenic patients with an intravascular catheter are at increased risk for infection with Staphylococcus epidermidis. During the intervals when the catheters are not being used for infusions, it is customary to maintain patency of the catheter lumen with a solution containing heparin. We show that heparin does not inhibit the growth of S. epidermidis isolated from the catheter of an infected patient. A 20-mg/ml solution of disodium EDTA, a chelating agent which effectively anticoagulates blood at this concentration, was shown to be bactericidal for an initial inoculum of 10(3) CFU of staphylococci per ml in 24 h. Vancomycin, an antibiotic which is often employed to treat Staphylococcus infections, was also bactericidal for initial inocula of 10(3) CFU/ml at doses of 6.7 micrograms/ml, a drug concentration in the therapeutic range. When 10(3) staphylococci per ml were cultured in the presence of catheter segments and disodium EDTA or vancomycin, subcultures of the catheters showed minimal or no growth, respectively. In contrast, when cultured with heparin alone, subcultures showed abundant growth. In view of its low cost, effectiveness as an anticoagulant, and bactericidal activity, EDTA should be studied as a replacement for heparin solutions for the maintenance of intravenous catheters in granulocytopenic patients. Images PMID:3150914

  9. G-protein-coupled receptor 35 is a target of the asthma drugs cromolyn disodium and nedocromil sodium.

    PubMed

    Yang, Yuhua; Lu, Jenny Ying-Lin; Wu, Xiaosu; Summer, Shamin; Whoriskey, John; Saris, Christiaan; Reagan, Jeff D

    2010-01-01

    We report that the asthma drugs cromolyn disodium and nedocromil sodium are potent G-protein-coupled receptor 35 (GPR35) agonists. We utilized calcium flux and inositol phosphate accumulation assays to examine the pharmacology of these asthma drugs on the human, mouse and rat GPR35. The compounds were more potent on the human GPR35 than on mouse and rat receptors. In contrast, zaprinast, a known GPR35 agonist, was more potent on mouse and rat GPR35 than the human ortholog. We show by quantitative PCR that GPR35 is expressed in human mast cells, human basophils and human eosinophils. We also demonstrate that GPR35 mRNA is upregulated upon challenge with IgE antibodies. We show that, unlike zaprinast, a potent phosphodiesterase 5 (PDE5) inhibitor, cromolyn disodium and nedocromil sodium lack inhibitory activity towards PDE5. These findings suggest that GPR35 may play an important role in mast cell biology and be a potential target for the treatment of asthma. Copyright 2010 S. Karger AG, Basel.

  10. 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. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. 21 CFR 73.3129 - Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulfonatophenyl]amino]-9,10-dihydro-9,10...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL LISTING OF COLOR ADDITIVES EXEMPT FROM...-dioxoanthracene-2-sulfonate. (a) Identity. The color additive is disodium 1-amino-4- -2-sulfonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulfonate (Reactive Blue 69) (CAS Reg. No. 70209-99-3, Colour...

  12. 21 CFR 73.3129 - Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulfonatophenyl]amino]-9,10-dihydro-9,10...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false Disodium 1-amino-4- -2-sulfonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulfonate. 73.3129 Section 73.3129 Food and Drugs FOOD AND DRUG... required to accomplish the intended coloring effect. (2) Authorization and compliance with this use...

  13. 21 CFR 73.3129 - Disodium 1-amino-4-[[4-[(2-bromo-1-oxoallyl)amino]-2-sulphonatophenyl]amino]-9,10-dihydro-9,10...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false Disodium 1-amino-4- -2-sulphonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulphonate. 73.3129 Section 73.3129 Food and Drugs FOOD AND DRUG... required to accomplish the intended coloring effect. (2) Authorization and compliance with this use...

  14. 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. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. [Effects of 18β-glycyrrhetinic Acid on the Expression of CCL11, AQP1 and EOS in Nasal Mucosa of Allergic Rhinitis Rats].

    PubMed

    Li, Juan-li; Xi, Ke-hu; Hou, Yun; Jiang, Ying; Gui, Yan; Wang, You-hu; Zhang, Fu-hong; Zhang, Xiao-bing

    2015-05-01

    To investigate the effects of 18β-glycyrrhetinic acid (GA) on the expression of eotaxin 1 (CCL11), aquaporin protein 1 (AQP1) and eosinophil (EOS) in nasal mucosa of allergic rhinitis (AR) rats. Seventy six Wistar rats were randomly divided into 4 groups, normal control (NC) group, AR model (AR) group, loratadine (LOA) group and 18β-GA group. All the mice in AR, LOA and 18β-GA groups were sensitized intraperitoneally with OVA and AL(OH), from day 1-14, then induced by intranasal administration with OVA from day 14-21, while the mice in NC group were sensitized with saline. The mice in both LOA and 18β-GA group were given LOA and 18β-GA once a day respectively from the 21 d, while the mice in AR and NC groups were administrated with saline. At the end of 1 week, 2 weeks and 3 weeks, the behavioral changes of mice were observed and recorded, the level of CCL11 mRNA was measured by RT-QPCR, and AQP1 expression was investiaged by SP staing. EOS in nasal mucosa was studied with the methods of HE staining. Compared with NC group, AR group showed typical AR symptoms. With the treatments, AR symptom scores and the expression levels of CCL11, AQP1 and EOS in nasal mucosa were improved significantly (P<0. 05). When compared with AR group, the above statistics in LOA group were down-regulated evidently at different points in time (P<. 05). At the end of 1 week, the above detection results in 18β-GA group were lower than those in AR group (P<0. 05). At the end of 2 weeks, those parameters approached to the levels of LOA and NC group significantly. 18β-GA administration could down-regulate the expression levels of CCL11, AQP1 and EOS in nasal mucosa of allergic rhinitis rats and cast effects on inhibiting the progress of AR.

  16. 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.

  17. Characteristics of Hepatic Schwannoma Presenting as an Unusual Multi-cystic Mass on Gadoxetic Acid Disodium-enhanced MR Imaging.

    PubMed

    Haradome, Hiroki; Woo, Jun; Nakayama, Hisashi; Watanabe, Haruna N; Ogawa, Masahiro; Moriyama, Mitsuhiko; Sugitani, Masahiko; Takayama, Tadatoshi; Abe, Osamu

    2017-02-13

    Hepatic schwannoma is a very rare hepatic tumor, usually appearing as a hypervascular solid mass with or without various degrees of cystic changes; however, to the best of our knowledge, only the two cases of hepatic schwannoma showing a multi-cystic appearance have previously been reported. We report herein a benign hepatic schwannoma presenting as an unusually large multi-cystic mass. The gadoxetic acid disodium-enhanced magnetic resonance imaging features are described with the histopathologic correlation and briefly review the literature. The solid-like areas showing the early/progressive enhancement, reflecting remnants of the Antoni A/B portion, during the dynamic phases may be helpful imaging features for the differentiation of other multi-cystic hepatic lesions, but pathological evaluation remains essential for diagnosis.

  18. The effects of disodium cromoglycate on enhanced adherence of Haemophilus influenzae to A549 cells infected with respiratory syncytial virus.

    PubMed

    Fukasawa, Chie; Ishiwada, Naruhiko; Ogita, Junko; Hishiki, Haruka; Kohno, Yoichi

    2009-08-01

    Nontypeable Haemophilus influenzae (NTHi) secondary infection often complicates respiratory syncytial virus (RSV) infections. Previous studies have revealed that RSV infections enhance NTHi adherence to airway epithelial cells. In this study, we investigated the effects of disodium cromoglycate (DSCG) and corticosteroids, which are frequently used for the treatment of wheezing often related to RSV infections, on the adherence of NTHi to RSV-infected A549 cells. DSCG inhibited enhanced adherence of NTHi to RSV-infected A549 cells, whereas dexamethasone (Dex) and fluticasone propionate (Fp) did not. DSCG suppressed the expression of ICAM-1, which is one of the NTHi receptors. Furthermore, DSCG exhibited an inhibitory effect on RSV infections. It is suggested that DSCG exerts an anti-RSV effect, and consequently attenuates the expression of NTHi receptors.

  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. Protective effect of ketotifen and disodium cromoglycate against bronchoconstriction induced by aspirin, benzoic acid or tartrazine in intolerant asthmatics.

    PubMed

    Wüthrich, B

    1979-01-01

    Oral challenge tests with acetylsalicylic acid, tartrazine or benzoic acid were performed in 7 intolerant asthmatic patients after a 3-day treatment with either orally taken ketotifen (1 mg twice daily) or inhaled disodium cromoglycate (20 mg four times daily) at random. Protection was noted with ketotifen in 5, with DSCG in 3 patients. On the evaluation of the mean percentage of the maximum decline in the forced expiratory volume in 1 sec (FEV1) only ketotifen afforded significant protection statistically (p less than 0.05). All the intolerant asthmatics studies showed, as an immunological abnormity, a slight, but significant decrease of the C1-inhibitor levels. Moreover, in three out of these the alpha 1-antitrypsin serum values were under the lower normal range.

  1. Disodium edetate as a promising interfacial material for inverted organic solar cells and the device performance optimization.

    PubMed

    Li, Xiaodong; Zhang, Wenjun; Wang, Xueyan; Gao, Feng; Fang, Junfeng

    2014-12-10

    Disodium edetate (EDTA-Na), a popular hexadentate ligand in analytical chemistry, was successfully introduced in organic solar cells (OSCs) as cathode interfacial layer. The inverted OSCs with EDTA-Na showed superior performance both in power conversion efficiency and devices stability compared with conventional devices. Interestingly, we found that the performance of devices with EDTA-Na could be optimized through external bias treatment. After optimization, the efficiency of inverted OSCs with device structure of ITO/EDTA-Na/polymer thieno[3,4-b]thiophene/benzodithiophene (PTB7):PC71BM/MoO3/Al was significantly increased to 8.33% from an initial value of 6.75%. This work introduces a new class of interlayer materials, small molecule electrolytes, for organic solar cells.

  2. Lysozyme/EDTA disodium salt and modified-atmosphere packaging to prolong the shelf life of burrata cheese.

    PubMed

    Conte, A; Brescia, I; Del Nobile, M A

    2011-11-01

    To prolong the shelf life of burrata cheese, we evaluated the effects of lysozyme and EDTA disodium salt (Na(2)-EDTA) with or without modified-atmosphere packaging (MAP) conditions. In particular, 3 concentrations of enzyme were combined with packaging in air and under MAP (95:5 CO(2):N(2)). The decline in quality of burrata cheese stored at 8°C was assessed by monitoring microbiological and sensory quality, in addition to pH and headspace composition. The combination of lysozyme/Na(2)-EDTA and MAP prolonged cheese shelf life, especially at the highest lysozyme concentration. In particular, the tested strategy was effective against microbial spoilage phenomena that appeared to be the quality factor that determine product unacceptability.

  3. Disodium Phosphonoacetate in Cream Base as a Possible Topical Treatment for Skin Lesions of Herpes Simplex Virus in Cebus Monkeys

    PubMed Central

    Palmer, Amos E.; London, William T.; Sever, John L.

    1977-01-01

    Disodium phosphonoacetate (PAA) in a cream-ointment base was applied to herpesvirus skin lesions on the genitalia of cebus monkeys. The lesions had been produced by the intradermal injection of herpes simplex virus type 2. Concentrations of 0.2, 2, and 5% PAA were used. Liberal application of PAA at concentrations of 2 and 5% proved extremely irritating and produced extensive, severe lesions over the treated area. The 2% PAA, when applied carefully to the lesion area, proved less irritating, but did not reduce healing time when compared with the placebo-treated animals. The 0.2% PAA caused slight reduction in lesion size and duration, but these differences were not statistically significant when compared with placebo-treated animals. PMID:411417

  4. Gadoxetate Disodium-Enhanced MRI to Differentiate Dysplastic Nodules and Grade of Hepatocellular Carcinoma: Correlation With Histopathology.

    PubMed

    Channual, Stephanie; Tan, Nelly; Siripongsakun, Surachate; Lassman, Charles; Lu, David S; Raman, Steven S

    2015-09-01

    The objective of our study was to determine quantitative differences to differentiate low-grade from high-grade dysplastic nodules (DNs) and low-grade from high-grade hepatocellular carcinomas (HCCs) using gadoxetate disodium-enhanced MRI. A retrospective study of 149 hepatic nodules in 127 consecutive patients who underwent gadoxetic acid-enhanced MRI was performed. MRI signal intensities (SIs) of the representative lesion ROI and of ROIs in liver parenchyma adjacent to the lesion were measured on unenhanced T1-weighted imaging and on dynamic contrast-enhanced MRI in the arterial, portal venous, delayed, and hepatobiliary phases. The relative SI of the lesion was calculated for each phase as the relative intensity ratio as follows: [mass SI / liver SI]. Of the 149 liver lesions, nine (6.0%) were low-grade DNs, 21 (14.1%) were high-grade DNs, 83 (55.7%) were low-grade HCCs, and 36 (24.2%) were high-grade HCCs. The optimal cutoffs for differentiating low-grade DNs from high-grade DNs and HCCs were an unenhanced to arterial SI of ≥ 0 or a relative SI on T2-weighted imaging of ≤ 1.5, with a positive predictive value (PPV) of 99.2% and accuracy of 88.6%. The optimal cutoffs for differentiating low-grade HCCs from high-grade HCCs were a relative hepatobiliary SI of ≤ 0.5 or a relative T2 SI of ≥ 1.5, with a PPV of 81.0% and an accuracy of 60.5%. Gadoxetate disodium-enhanced MRI allows quantitative differentiation of low-grade DNs from high-grade DNs and HCCs, but significant overlap was seen between low-grade HCCs and high-grade HCCs.

  5. Simultaneous (68)Ga-DOTA-TOC PET/MRI with gadoxetate disodium in patients with neuroendocrine tumor.

    PubMed

    Hope, Thomas A; Pampaloni, Miguel Hernandez; Nakakura, Eric; VanBrocklin, Henry; Slater, James; Jivan, Salma; Aparici, Carina Mari; Yee, Judy; Bergsland, Emily

    2015-08-01

    To evaluate a simultaneous PET/MRI approach to imaging patients with neuroendocrine tumor using a combination of (68)Ga-DOTA-TOC as a PET contrast agent and gadoxetate disodium as a hepatobiliary MRI contrast agent. Ten patients with neuroendocrine tumor with known or suspected hepatic disease were imaged using a (68)Ga-DOTA-TOC PET/CT immediately followed by a 3.0T time-of-flight PET/MRI, using a combined whole body and liver specific imaging. The presence of lesions and DOTA-TOC avidity were assessed on CT, PET from PET/CT, diffusion weighted imaging, hepatobiliary phase imaging (HBP), and PET from PET/MRI. Maximum standardized uptake values (SUVmax) in hepatic lesions and nodal metastases were compared between PET/CT and PET/MRI, as were detection rates using each imaging approach. A total of 101 hepatic lesions were identified, 47 of which were DOTA-TOC avid and able to be individually measured on both PET/CT and PET/MRI. HBP imaging had a higher sensitivity for detection of hepatic lesions compared to CT or PET (99% vs. 46% and 64%, respectively; p values <0.001). There was a strong correlation between SUVmax of liver lesions obtained with PET/CT compared to PET/MR imaging (Pearson's correlation = 0.91). For nodal disease, CT had a higher sensitivity compared to whole body MRI (p = 0.015), although PET acquired from PET/MRI detected slightly more lesions compared to PET from PET/CT. A simultaneous PET/MRI using both (68)Ga-DOTA-TOC and gadoxetate disodium was successful in whole body staging of patients with neuroendocrine tumor. HBP imaging had an increased detection rate for hepatic metastases.

  6. 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. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Graphene oxide and creatine phosphate disodium dual template-directed synthesis of GO/hydroxyapatite and its application in drug delivery.

    PubMed

    Yao, Chengli; Zhu, Jinmiao; Xie, Anjian; Shen, Yuhua; Li, Hongying; Zheng, Bin; Wei, Yanxin

    2017-04-01

    In this study, graphene oxide and creatine phosphate disodium acted as dual template and was employed to synthesize graphene oxide (GO)/hydroxyapatite (HA) hybrids as drug carriers. In the rapid preparation of GO/HA hybrids, creatine phosphate disodium salt (CPDS) severed as a phosphorus source and graphene oxide acted as a template in aqueous solution. The effects of the reaction temperature, time and pH value of the aqueous solution on the morphology of the product were investigated. The result showed that the hydrolysis of CPDS under hydrothermal condition played an important role in the formation of hierarchical hollow GO/HA hybrids. The GO nanosheets provided reactive sites for the binding of HA nanoparticles and absorbing ibuprofen (IBU) molecules. The GO/HA hybrids had ideal sustained drug-release behavior. It indicated that the prepared GO/HA hybrids may be promising materials for applications in biomedical area. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. 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. Crown Copyright © 2012. Published by Elsevier GmbH. All rights reserved.

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

    PubMed

    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.

  10. 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

  11. 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.

  12. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: the TACT randomized trial.

    PubMed

    Lamas, Gervasio A; Goertz, Christine; Boineau, Robin; Mark, Daniel B; Rozema, Theodore; Nahin, Richard L; Lindblad, Lauren; Lewis, Eldrin F; Drisko, Jeanne; Lee, Kerry L

    2013-03-27

    Chelation therapy with disodium EDTA has been used for more than 50 years to treat atherosclerosis without proof of efficacy. To determine if an EDTA-based chelation regimen reduces cardiovascular events. Double-blind, placebo-controlled, 2 × 2 factorial randomized trial enrolling 1708 patients aged 50 years or older who had experienced a myocardial infarction (MI) at least 6 weeks prior and had serum creatinine levels of 2.0 mg/dL or less. Participants were recruited at 134 US and Canadian sites. Enrollment began in September 2003 and follow-up took place until October 2011 (median, 55 months). Two hundred eighty-nine patients (17% of total; n=115 in the EDTA group and n=174 in the placebo group) withdrew consent during the trial. Patients were randomized to receive 40 infusions of a 500-mL chelation solution (3 g of disodium EDTA, 7 g of ascorbate, B vitamins, electrolytes, procaine, and heparin) (n=839) vs placebo (n=869) and an oral vitamin-mineral regimen vs an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Fifteen percent discontinued infusions (n=38 [16%] in the chelation group and n=41 [15%] in the placebo group) because of adverse events. The prespecified primary end point was a composite of total mortality, recurrent MI, stroke, coronary revascularization, or hospitalization for angina. This report describes the intention-to-treat comparison of EDTA chelation vs placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was P = .036. Qualifying previous MIs occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, and 31% were diabetic. The primary end point occurred in 222 (26%) of the chelation group and 261 (30%) of the placebo group (hazard ratio [HR], 0.82 [95% CI, 0.69-0.99]; P = .035). There was no effect on total mortality (chelation: 87 deaths [10%]; placebo, 93 deaths [11%]; HR, 0

  13. Effect of disodium EDTA chelation regimen on cardiovascular events in patients with previous myocardial infarction: The TACT Randomized Trial

    PubMed Central

    Lamas, Gervasio A.; Goertz, Christine; Boineau, Robin; Mark, Daniel B.; Rozema, Theodore; Nahin, Richard L.; Lindblad, Lauren; Lewis, Eldrin F.; Drisko, Jeanne; Lee, Kerry L.

    2014-01-01

    Context Chelation therapy with disodium ethylene diamine tetraacetic acid (EDTA) has been used for over 50 years to treat atherosclerosis without proof of efficacy. Objective To determine if an EDTA-based chelation regimen reduces cardiovascular events. Design and Setting Double-blind placebo-controlled 2×2 factorial multicenter randomized trial. NIH Funding was approved in August 2002. The first patient was enrolled in September 2003, and the last follow-up took place in October 2011. Median follow-up was 55 months. Participants were recruited from 134 US and Canadian clinical sites. Participants 1708 patients, age 50 or older and at least 6 weeks post myocardial infarction, with a serum creatinine <2.0 mg/dL. 289 patients (17% of total; 115 in the EDTA group and 174 in the placebo group) withdrew consent for continued follow-up over the course of the trial. Interventions Patients were randomized to receive 40 infusions of a 500 mL chelation solution (containing 3 grams of disodium EDTA, 7 grams of ascorbate, B-vitamins, electrolytes, procaine, and heparin) versus placebo, and to an oral vitamin and mineral regimen or an oral placebo. Infusions were administered weekly for 30 weeks, followed by 10 infusions 2 to 8 weeks apart. Patients received 55,222 infusions. 15% discontinued infusions for adverse events. Main outcome measure The pre-specified primary endpoint was a composite of total mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina. Followup for clinical events began upon randomization. This report describes the intent-to-treat comparison of EDTA chelation versus placebo. To account for multiple interim analyses, the significance threshold required at the final analysis was p=0.036. Results The qualifying myocardial infarction occurred a median of 4.6 years before enrollment. Median age was 65 years, 18% were female, 9% were nonwhite, 31% were diabetic. 83% had prior coronary revascularization, and

  14. 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.

  15. 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.

  16. Disodium Cromoglycate Reverses Colonic Visceral Hypersensitivity and Influences Colonic Ion Transport in a Stress-Sensitive Rat Strain

    PubMed Central

    Carroll, Siobhan Yvonne; O’Mahony, Siobhain Mary; Grenham, Susan; Cryan, John Francis; Hyland, Niall Patrick

    2013-01-01

    The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders. PMID:24367692

  17. The effects of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDA) on the delayed nasal mucosa response to allergen challenge.

    PubMed

    Pelikan, Z

    1984-02-01

    The protective effects of disodium cromoglycate (DSCG) and beclomethasone dipropionate (BDA) on the "delayed nasal response" to allergen challenge (DNR) were investigated in 37 patients with allergic rhinitis. These thirty-seven patients, from a group of 268, developed 43 "delayed nasal responses" (DNR), 16 cases of "isolated delayed responses" (IDNR) and 27 cases of "dual delayed responses" (DDNR), where the delayed response (DLDNR) was preceded by an immediate response (INR). BDA demonstrated significant protective effects on the DNR in both its modifications; however, to a higher degree in the case of the IDNR. DSCG significantly decreased only the INR, being a part of the DDNR, while in the case of the DNR in both its modifications, DSCG was completely ineffective. It is suggested that BDA should be the drug of first choice in allergic rhinitis patients demonstrating the DNR. When immediate responses to the same or other allergens are also present, DSCG should be added at the beginning of the treatment for a temporary period of a few months.

  18. Comparison of levocabastine, a new selective H1-receptor antagonist, and disodium cromoglycate, in a nasal provocation test with allergen.

    PubMed Central

    Kolly, M; Pécoud, A

    1986-01-01

    The effect of intranasal administration of levocabastine, a new selective H1-receptor antagonist, was investigated in a nasal provocation test (NPT) performed with allergens. The NPT allowed a quantitative estimation of the nasal allergic threshold (concentration of allergen necessary to trigger the reaction). In addition, the intensity of the three major rhinitis symptoms (obstruction, rhinorrhea and sneezing) was determined. Twelve adult patients, allergic to grass pollen, underwent a first NPT without pretreatment ('initial NPT'); the NPT was then repeated after the single intranasal administration of either placebo, 8 mg disodium cromoglycate (DSCG) or 0.2 mg levocabastine in a double-blind random order. The NPTs gave reproducible results since both the threshold and symptom intensities were similar in the initial NPT and in the NPT performed after placebo. The reaction threshold increased in 8/12 patients after DSCG (0.05 less than P less than 0.1) and in 9/12 patients after levocabastine (P less than 0.05). Levocabastine clearly inhibited rhinorrhea (P less than 0.001) and sneezing (P less than 0.02) but did not influence the nasal obstruction. DSCG inhibited rhinorrhea only (P less than 0.01). The intranasal administration of levocabastine might be useful in the treatment of allergic rhinitis. PMID:2876723

  19. Kinetics of the alkaline phosphatase catalyzed hydrolysis of disodium p-nitrophenyl phosphate in frozen model systems.

    PubMed

    Terefe, Netsanet Shiferaw; Mokwena, Kereilemang Khanah; Loey, Ann Van; Hendrickx, Marc E

    2002-01-01

    The alkaline phosphatase catalyzed hydrolysis of disodium-p-nitrophenyl phosphate was studied in four model systems comprising sucrose, maltodextrin, carboxymethylcellulose (CMC), and CMC-lactose in a temperature range of -28 to 20 degrees C. In the maltodextrin and CMC-lactose model systems, the reaction rate decreased to a very low value as the glass transition temperature was approached. In the CMC and CMC-lactose systems with low initial solute concentration, as a consequence of freeze-concentration, a rate maximum around the initial freezing temperature was observed. The Arrhenius equation described the temperature dependence of the reaction rate both in the liquid and the glassy states in all systems studied, while a slightly curved Arrhenius plot was observed in the "rubbery" state of the CMC and CMC-lactose systems. The WLF equation with system-dependent coefficients described the kinetics in the rubbery state of all the model systems except sucrose, excluding the short temperature range where reaction rate enhancement with decreasing temperature was observed.

  20. 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.

  1. Hypophosphatemic rickets developed after treatment with etidronate disodium in a patient with generalized arterial calcification in infancy.

    PubMed

    Miyai, Kentaro; Ariyasu, Daisuke; Numakura, Chikahiko; Yoneda, Kaori; Nakazato, Hitoshi; Hasegawa, Yukihiro

    2015-12-01

    Ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) was originally reported as a responsible gene for generalized arterial calcification in infancy (GACI). Though the prognosis of GACI patients is poor because of myocardial infarction and heart failure in relation to medial calcification of the coronary arteries, some patients rescued by bisphosphonate treatment have been reported. Recently, ENPP1 is also reported as responsible for autosomal recessive hypophosphatemic rickets type 2. We show here a boy with homozygous ENPP1 mutations diagnosed as having GACI in early infancy. After the diagnosis, he was treated with etidronate disodium (EHDP) in combination with antihypertensive drugs. The calcification of major arteries was diminished and disappeared by the age of eight months. He also showed mild hypophosphatemia (2.6-3.7 mg/dl) from the age of one year. After the treatment with EHDP for five years, he showed genu valgum with hypophosphatemia (2.6 mg/dl). He was diagnosed as having hypophosphatemic rickets at the age of seven years. The findings that hyper-mineralization of the arteries and hypo-mineralization of the bone observed in the same patient are noteworthy. ENPP1 could be regarded as a controller of the calcification of the whole body at least in part.

  2. Mechanism of oxidation of 3-hydroxy-2,7-naphthalenedisulfonic acid disodium salt with oxygen in subcritical water.

    PubMed

    Imbierowicz, Mirosław

    2017-06-01

    The article presents the results of studies on the oxidation mechanism of 3-hydroxy-2,7-naphthalenedisulfonic acid disodium salt (R-salt) with oxygen in subcritical water. To this aim, a series of experiments were carried out which showed that at a temperature of 413 K and pH > 9 the oxidation reaction of a substrate with oxygen was relatively quick and after approximately 40 min the R-salt oxidation yield exceeded 95%. In an acidic medium (pH < 7), the rate of R-salt oxidation is small. In order to identify the mechanism of R-salt oxidation, experiments were carried out at 413-569 K in solutions with pH = 10.0 and at partial oxygen pressure pO2 = 1.73 MPa. As a result of these experiments, a stable oxidation product was isolated from the reaction mixture and subjected to spectroscopic analysis. The analysis of (H)NMR of this product proved that a stable intermediate product of R-salt oxidation was 4-sulfophthalic acid sodium salt. The results of the experiments have shown that destructive oxidation of R-salt can easily be obtained at a temperature of 413 K, but satisfactory reduction of TOC in wastewater containing this substrate requires the use of very high temperature: at 569 K only 60% reduction of TOC was achieved.

  3. Behavior of heavy metals in human urine and blood following calcium disodium ethylenediamine tetraacetate injection: observations in metal workers.

    PubMed

    Sata, F; Araki, S; Murata, K; Aono, H

    1998-06-12

    To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the "circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.

  4. Erythrocyte ALA-d activity in experimentally lead-poisoned ducks and its change during treatment with disodium calcium EDTA.

    PubMed

    Murase, T; Horiba, N; Goto, I; Yamato, O; Ikeda, T; Sato, K; Jin, K; Inaba, M; Maede, Y

    1993-09-01

    To determine useful procedures for the diagnosis and prognosis of lead poisoning in waterfowl caused by ingestion of lead pellets, erythrocyte delta-aminolevulinic acid dehydratase (ALA-d) was investigated in experimentally lead-poisoned ducks. A highly positive correlation was observed between the concentration of blood lead and the ALA-d activity ratio (the ratio of activated:non-activated enzyme activity) in those birds given seven lead pellets (3 mm diameter). The ALA-d activity ratio rapidly increased after the administration of lead pellets, but began to fall immediately after the initiation of disodium calcium ethylenediamine tetra-acetate (CaEDTA) therapy which resulted in a rapid decrease in the concentration of lead in the blood of these birds. In contrast, the ALA-d activity remained inhibited even after blood lead levels began to decrease following treatment. These results demonstrated that the ALA-d activity ratio is a very useful and sensitive indicator for the diagnosis and evaluation of therapeutic effects after lead poisoning in waterfowl.

  5. Recovery from lead induced biochemical and immunological alterations following combined treatment with DMSA and calcium disodium EDTA in rats.

    PubMed

    Flora, G J; Kumar, P; Seth, P K

    1998-03-01

    The therapeutic potential of meso 2,3-dimercaptosuccinic acid (DMSA) and calcium disodium ethylenediamine tetraacetic acid (CaNa(2)EDTA) alone or in combination in reducing levels of lead in blood and other soft organs and reversing lead induced biochemical and immunological alterations were investigated after chronic low level lead exposure. Lead exposure produced a significant adverse effect on few selected haematopoietic, nervous, testicular and immunological variables. Conventional 5-day treatment with both DMSA and CaNa(2)EDTA individually was effective in inducing elimination of lead but the recovery of the altered biochemical and clinical indices was moderate. When given in combination for 5 days, (DMSA was administered orally twice daily before intraperitoneal CaNa(2)EDTA administration) they were more effective in depleting body lead burden and providing recoveries in the altered biochemical parameters. Along with the rapid removal of lead from body stores after combined treatment, the immunological variables also recovered spontaneously. However, the altered CNS disorders remained practically unchanged following 5 days of chelation therapy. Lead induced testicular alterations also showed some recoveries after combined treatment. The results indicate that combined DMSA and CaNa(2)EDTA treatment could be more beneficial than individual treatment with any of these agents.

  6. The disodium salt of EDTA inhibits the binding of vasoactive intestinal peptide to macrophage membranes: endodontic implications.

    PubMed

    Segura, J J; Calvo, J R; Guerrero, J M; Sampedro, C; Jimenez, A; Llamas, R

    1996-07-01

    The purpose of this study was to investigate the effect of the disodium salt of ethylenediamine tetraacetate (EDTA), a calcium ion chelator used in the root canal therapy, on vasoactive intestinal peptide (VIP) binding to macrophage membranes (MM's). Binding assays were conducted at 15 degrees C in 0.5 ml of 50 mM Tris-HCl buffer (pH 7.5) containing 1.6% (w/v) bovine serum albumin, 1.2 mg/ml of bacitracin, and different EDTA concentrations, using 45 pM of [125I]VIP as tracer. Results showed that EDTA inhibits VIP binding to MM's in a dose-dependent manner, with an IC50 value of 5.4 mM (p < 0.01). EDTA concentrations equal or higher than 100 mM of abolished VIP-MM interaction. Taking into account that the macrophage plays an essential role in inflammatory reactions and the immune response, we conclude that the apical extrusion of EDTA during root canal therapy could modify VIP-macrophage interaction modulating the inflammatory mechanisms involved in periapical lesions.

  7. Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain.

    PubMed

    Carroll, Siobhan Yvonne; O'Mahony, Siobhain Mary; Grenham, Susan; Cryan, John Francis; Hyland, Niall Patrick

    2013-01-01

    The interface between psychiatry and stress-related gastrointestinal disorders (GI), such as irritable bowel syndrome (IBS), is well established, with anxiety and depression the most frequently occurring comorbid conditions. Moreover, stress-sensitive Wistar Kyoto (WKY) rats, which display anxiety- and depressive-like behaviors, exhibit GI disturbances akin to those observed in stress-related GI disorders. Additionally, there is mounting preclinical and clinical evidence implicating mast cells as significant contributors to the development of abdominal visceral pain in IBS. In this study we examined the effects of the rat connective tissue mast cell (CTMC) stabiliser, disodium cromoglycate (DSCG) on visceral hypersensitivity and colonic ion transport, and examined both colonic and peritoneal mast cells from stress-sensitive WKY rats. DSCG significantly decreased abdominal pain behaviors induced by colorectal distension in WKY animals independent of a reduction in colonic rat mast cell mediator release. We further demonstrated that mast cell-stimulated colonic ion transport was sensitive to inhibition by the mast cell stabiliser DSCG, an effect only observed in stress-sensitive rats. Moreover, CTMC-like mast cells were significantly increased in the colonic submucosa of WKY animals, and we observed a significant increase in the proportion of intermediate, or immature, peritoneal mast cells relative to control animals. Collectively our data further support a role for mast cells in the pathogenesis of stress-related GI disorders.

  8. Intravenous and intramuscular pharmacokinetics of a single-daily dose of disodium-fosfomycin in cattle, administered for 3 days.

    PubMed

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

    2007-02-01

    Pharmacokinetic parameters of fosfomycin in cattle were determined after administration of buffered disodium fosfomycin either intravenously (i.v.) or intramuscularly (i.m.) at a dose of 20 mg/kg/day for 3 days. Calculated concentrations at time zero and maximum serum concentrations were 34.42 and 10.18 mug/mL, respectively. The variables determined, the elimination half-life of the drug remained unchanged during the 3 days ( = 1.33 +/- 0.3 h for the i.v. route and = 2.17 +/- 0.4 h for the i.m. route). Apparent volumes of distribution suggest moderated distribution out of the central compartment (V(darea) = 673 mL +/- 27 mL/kg and V(dss) = 483 +/- 11 mL/kg). Bioavailability after i.m. administration was 74.52%. Considering fosfomycin as a time-dependent antibacterial drug, plasma concentration vs. time profiles obtained in this study, suggest that clinically effective plasma concentrations of fosfomycin could be obtained for up to 8 h following i.v. administration and approximately 10 h after i.m. injection of 20 mg/kg, for susceptible bacteria. In addition to residue studies in milk and edible tissues, a series of clinical assessments, using fosfomycin at 20 mg/kg b.i.d. or t.i.d. are warranted before this antibacterial drug should be considered for use in cattle.

  9. 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.

  10. Evaluation of the impact of tromethamine edetate disodium dihydrate on antimicrobial susceptibility of Pseudomonas aeruginosa in biofilm in vitro.

    PubMed

    Pye, Charlotte C; Singh, Ameet; Weese, J Scott

    2014-04-01

    Biofilm formation by Pseudomonas aeruginosa has been documented in canine otic isolates. An increase in minimal inhibitory concentration (MIC) for specific antibiotics has been noted for biofilm-embedded bacteria. Tromethamine edetate disodium dihydrate buffered to pH 8 with tromethamine hydrochloride and deionized water (Triz-EDTA(®)) has been documented to potentiate bactericidal activity when used in combination with topical antibiotics, but the impact on biofilm-embedded bacteria is unknown. The objective of this study was to evaluate the impact of Triz-EDTA(®) use on in vitro antimicrobial susceptibility of biofilm-embedded P. aeruginosa. Biofilm formation was documented using a microtitre plate assay. Broth microdilution was used to assess the MIC of neomycin, polymyxin B, enrofloxacin and gentamicin for the biofilm-embedded bacteria. The microtitre plate assay was again used to assess the MIC of neomycin, polymyxin B, enrofloxacin and gentamicin for biofilm-embedded bacteria with added Triz-EDTA(®). Thirty-one isolates from dogs with otitis were tested. Addition of Triz-EDTA(®) significantly reduced MICs for neomycin (P < 0.003) and gentamicin (P < 0.02) but not for polymyxin B (P = 0.3). Enrofloxacin MICs increased in the presence of Triz-EDTA (P < 0.036). Triz-EDTA(®) may be a useful adjunctive treatment for chronic cases of Pseudomonas otitis where biofilms may have developed, if gentamicin or neomycin is to be used as a topical treatment. In vivo study is required to confirm this effect. © 2014 ESVD and ACVD.

  11. Effect of disodium cromoglycate (DSCG) and antihistamines on postirradiation 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.

    1988-02-01

    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. However, the postirradiation plasma histamine levels in both irradiated groups showed an increase of approximately 1600% above the preirradiation levels and the postirradiation control levels.

  12. The significance of chloride in the inhibitory action of disodium cromoglycate on immunologically-stimulated rat peritoneal mast cells.

    PubMed

    Law, J K Y; Yeung, C K; Wan, S P; Ingebrandt, S; Lau, H Y A; Rudd, J A; Chan, M

    2011-09-01

    The microelectrode array (MEA) was used to investigate the pharmacological relevance of chloride (Cl-) ions in antigen-dependent mast cell activation and the inhibitory effect of disodium cromoglycate (DSCG) on mast cell activation. The movements of ions across the cellular membrane and the potential relationship between Cl- channels and DSCG during immunological activation were investigated using the MEA. The results were then subsequently compared with the amount of histamine released from anti-IgE activated peritoneal mast cells. The inclusion of charybdotoxin (ChTX) in Cl--free buffer showed that the measured field potentials during antigen-stimulated peritoneal mast cell were a combination of Cl- influx and K+ efflux. The delayed onset time of Cl- influx indicated the presence of a delayed outwardly-rectifying Cl- current in the antigen-stimulated peritoneal mast cells. The use of 5-nitro-2-(3-phenylpropylamino) benzoic acid demonstrated that the activated mast cell membrane potential can be stabilised, thereby reducing the amount of histamine released from the anti-IgE activated mast cells. The correlation between the results of the histamine release assay and the electrophysiological measurements demonstrated the importance of Cl- to anti-IgE dependent mast cell activation. The inhibitory effect of DSCG on anti-IgE activated cells, however, did not correlate with the presumed influx of Cl-. The MEA data suggest that Cl- influx is crucial to IgE-dependent mast cell degranulation. While the MEA cannot yield information about single channel properties, it is convenient to use and can provide information on the global changes in electrophysiological responses of non-excitable cells. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Effect of disodium cromoglycate (DSCG) and antihistamines on postirradiation cerebral blood flow and plasma levels of histamine and neurotensin.

    PubMed

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

    1988-02-01

    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. However, the postirradiation plasma histamine levels in both irradiated groups showed an increase of approximately 1600% above the preirradiation levels and the postirradiation control levels. These findings implicate histamine in the postirradiation hypotension, but not necessarily in the direct responsibility for the decrease in regional cerebral blood flow seen immediately postirradiation in the primate.

  14. Prevention of mast cell degranulation by disodium cromoglycate delayed the regression of hypoxic pulmonary hypertension in rats.

    PubMed

    Maxová, Hana; Vasilková, Marianna; Novotná, Jana; Vajnerová, Olga; Bansová, Alena; Vízek, Martin; Herget, Jan

    2010-01-01

    Pulmonary vascular remodeling induced by chronic hypoxia regresses after return to normoxia. This regression is associated with an increased amount of collagenase in pulmonary mast cells and increased collagenolytic and elastolytic activity in the lung tissue. The role of lung mast cells during recovery from chronic hypoxia was tested by the inhibition of their degranulation by disodium cromoglycate (DSCG). Male Wistar rats (n = 46) were exposed to isobaric hypoxia (3 weeks, F(i)O(2) 0.1). Thirteen of them were tested immediately at the end of exposure, 17 were treated with DSCG during the first 4 days of recovery and tested on the 5th or 14th day of recovery, 16 untreated animals were measured at the same time intervals. These groups were compared with 12 animals kept in normoxia. The rats were anesthetized (Thiopental) and their pulmonary arterial blood pressure (PAP), cardiac output and heart weight were tested, as well as the collagen composition of the walls of the peripheral pulmonary arteries. DSCG applied during the first 4 days of recovery from chronic hypoxia blocked the decrease in PAP during the early phase of recovery and had no influence on PAP at a later phase. DSCG administration prevents collagen splitting in peripheral pulmonary vessels at the early phase of recovery. PAP and right ventricle hypertrophy were normalized after 14 days of return to normoxia. Mast cell degranulation plays a role in the regression of pulmonary hypertension during the early phase of recovery from chronic hypoxia. Copyright © 2010 S. Karger AG, Basel.

  15. Preclinical Studies to Predict Efficacy of Vascular Changes Induced by Combretastatin A-4 Disodium Phosphate in Patients

    SciTech Connect

    Nielsen, Thomas Murata, Rumi; Maxwell, Ross J.; Stodkilde-Jorgensen, Hans; Ostergaard, Leif; Horsman, Michael R.

    2008-03-01

    Purpose: To determine how combretastatin A-4 disodium phosphate (CA4DP) dose-dependent changes in radiation response of a C3H mouse mammary carcinoma relate to measurements of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters and how those mouse DCE-MRI results compare with published clinical DCE-MRI data. Methods and Materials: C3H mammary carcinomas grown in female CDF{sub 1} mice were treated when at 200 mm{sup 3} in size. Groups of mice were given graded radiation doses, either alone or followed 30 min later by an intraperitoneal injection of CA4DP, administered at doses of 10-250 mg/kg. The radiation dose producing local tumor control in 50% of treated animals at 90 days (TCD{sub 50}) was calculated for each CA4DP dose. DCE-MRI was performed before and 3 h after CA4DP administration, and parameters describing vascularity and interstitial volume were estimated. Results: TCD{sub 50} showed a dose-dependent decrease reaching significance at 25 mg/kg. At greater doses of 50 and 100 mg/kg, the TCD{sub 50} increased slightly and was not significantly different from that of controls. TCD{sub 50} significantly decreased again at 250 mg/kg. The drug dose-response curves for all post-treatment vascular DCE-MRI parameters showed a shape similar to that of the TCD{sub 50} curve. A similar dose dependency was seen with previously published clinical data. Conclusion: Our preclinical DCE-MRI data could predict the CA4DP enhancement of the tumor radiation response and suggest the clinical CA4DP doses necessary to improve the radiation response in patients.

  16. 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.

  17. Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate.

    PubMed

    Xu, Zhen; Mansour, Heidi M; Mulder, Tako; McLean, Richard; Langridge, John; Hickey, Anthony J

    2010-08-01

    The major objective of this study was: discriminatory assessment of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs. Drug/lactose interactive physical mixtures (2%w/w) were prepared. Their properties were measured: solid-state characterization of phase behavior and molecular interactions by differential scanning calorimetry and X-ray powder diffraction; particle morphology and size by scanning electron microscopy and laser diffraction; aerosol generation by SETs and characterization by twin-stage liquid impinger and Andersen cascade impactor operated at 60 L/min. The fine particle fraction (FPF) was correlated with SET shear stress (tau(s)), using a novel powder aerosol deaggregation equation (PADE). Drug particles were <5 microm in volume diameter with narrow unimodal distribution (Span <1). The lowest shear SET (tau(s) = 0.624 N/m(2)) gave a higher emitted dose (ED approximately 84-93%) and lower FPF (FPF(6.4) approximately 7-25%). In contrast, the highest shear SET (tau(s) = 13.143 N/m(2)) gave a lower ED (ED approximately 75-89%) and higher FPF (FPF(6.4) approximately 15-46%). The performance of disodium cromoglycate was superior to albuterol sulfate at given tau(s), as was milled with respect to sieved lactose monohydrate. Excellent correlation was observed (R(2) approximately 0.9804-0.9998) when pulmonary drug particle release from the surface of lactose carriers was interpreted by PADE linear regression for dry powder formulation evaluation and performance prediction. (c) 2010 Wiley-Liss, Inc. and the American Pharmacists Association

  18. 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.

  19. Conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid as Pin1 inhibitors displaying anti-prostate cancer ability.

    PubMed

    Li, Kun; Ma, Tianyi; Cai, Jingjing; Huang, Min; Guo, Hongye; Zhou, Di; Luan, Shenglin; Yang, Jinyu; Liu, Dan; Jing, Yongkui; Zhao, Linxiang

    2017-08-04

    Twenty-six conjugates of 18β-glycyrrhetinic acid derivatives with 3-(1H-benzo[d]imidazol-2-yl)propanoic acid were designed and synthesized as Pin1 inhibitors. Most of these semi-synthetic compounds showed improved Pin1 inhibitory activity and anti-proliferative effects against prostate cancer cells as compared to 3-(1H-benzo[d]imidazol-2-yl)propanoic acid and GA. Compounds 10a and 12i were the most potent to inhibit growth of prostate cancer PC-3 with GI50 values of 7.80μM and 3.52μM, respectively. The enzyme inhibition ratio of nine compounds at 10μM was over 90%. Structure-activity relationships indicated that both appropriate structure at ring C of GA and suitable length of linker between GA skeleton and benzimidazole moiety had significant impact on improving activity. Western blot assay revealed that 10a decreased the level of cell cycle regulating protein cyclin D1. Thus, these compounds might represent a novel anti-proliferative agent working through Pin1 inhibition. Copyright © 2017. Published by Elsevier Ltd.

  20. Pseudolesion of the liver observed on gadoxetate disodium-enhanced magnetic resonance imaging obtained shortly after transarterial chemoembolization for hepatocellular carcinoma.

    PubMed

    Shinagawa, Yoshinobu; Sakamoto, Keiko; Fujimitsu, Ritsuko; Ida, Mikiko; Urakawa, Hiroshi; Kora, Shin-Ichi; Higashihara, Hideyuki; Takano, Kouichi; Yoshimitsu, Kengo

    2010-07-01

    The purpose of this report was to describe pseudolesions of the liver that mimicked residual hypervascular hepatocellular carcinoma (HCC), as observed on gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) obtained shortly after transarterial chemoembolization (TACE). Between June 2008 and December 2008, three patients underwent MRI within 12 days after TACE to rule out remaining viable cancerous tissue or to assess the treatment effect. In all three patients, nontumorous liver tissue adjacent to the treated HCC exhibited focal arterial enhancement on dynamic phase and subsequent diminished uptake of gadoxetate disodium on hepatocellular phase images, which mimicked residual HCC. All three patients had mild postembolization syndrome at the time of EOB-MRI and showed no evidence of residual or recurrent tumors on follow-up. The findings of these areas may represent transient focal hyperemia and damage to the liver cell function caused by TACE. Radiologists should be aware that EOB-MRI obtained shortly after TACE may show pseudolesions around the treated tumors and should not mistake them for residual or recurrent tumors.

  1. Disodium cromoglycate inhibits S mu-->S epsilon deletional switch recombination and IgE synthesis in human B cells

    PubMed Central

    1994-01-01

    IgE synthesis requires interleukin 4 (IL-4) and a T-B cell interaction that involves the B cell antigen CD40 and its ligand expressed on activated T cells. IL-4 induces epsilon germline transcription whereas ligation of CD40 results in deletional S mu-->S epsilon switch recombination, expression of mature epsilon transcripts, and IgE synthesis and secretion. We demonstrate that disodium cromoglycate (DSCG), a drug commonly used for the prophylactic treatment of allergic disease, inhibits T cell-driven IgE synthesis by human B cells at concentrations readily achievable in the course of inhaled therapy for asthma. Inhibition of IgE synthesis by DSCG was not the result of drug toxicity because DSCG did not affect the viability of T and B cells or their proliferation to mitogens. DSCG did not interfere with CD40 ligand expression by T cells but clearly targeted the B cells because it inhibited IgE synthesis induced by anti-CD40 and IL-4 in populations of highly purified B cells. DSCG had no effect on the induction of epsilon germline transcripts by IL-4 but strongly inhibited CD40 mediated S mu-->S epsilon deletional switch recombination in IL-4- treated B cells as assayed by nested primer PCR. The effect of DSCG was not specific for CD40-mediated induction of IgE isotype switching because DSCG inhibited IgE synthesis as well as S mu-->S epsilon deletional switch recombination induced by hydrocortisone and IL-4 in B cells. Moreover, the effect of DSCG was not specific for IgE isotype switching because DSCG inhibited the synthesis of IgG4 by B cells sorted for lack of surface expression of IgG4 and stimulated with anti- CD40 and IL-4. DSCG caused only minimal inhibition (< 15%) of spontaneous IgE synthesis by lymphocytes from patients with the hyper- IgE syndrome and did not affect pokeweed mitogen-induced IgG and IgA synthesis by lymphocytes suggesting that it has little effect on B cells that have already undergone isotype switching. These results indicate that DSCG

  2. 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

  3. Comparison of dimercaptosuccinic acid and calcium disodium ethylenediaminetetraacetic acid versus dimercaptopropanol and ethylenediaminetetraacetic acid in children with lead poisoning.

    PubMed

    Besunder, J B; Super, D M; Anderson, R L

    1997-06-01

    To compare the response to dimercaptopropanol (BAL) and calcium disodium ethylenediaminetetraacetic acid (EDTA) versus orally administered meso-2,3-dimercaptosuccinic acid (DMSA) and EDTA in children with lead poisoning. Retrospective review of medical records of children admitted to MetroHealth Medical Center with a whole blood lead (BPb) concentration of 2.17 mumol/L (45 micrograms/dl) or more (or less than 2.17 mumol/L and not a candidate for outpatient oral chelation) and treated with BAL + EDTA or DMSA + EDTA. In each group, the mean BPb values at the end of therapy and at 14 and 33 days after chelation were compared with pretreatment BPb by the Wilcoxon signed-rank test, whereas the Mann-Whitney U test was used to compare percentage change from pretreatment at each follow-up day between the two groups. Twenty-three children received BAL + EDTA and 22 received DMSA + EDTA. The BPb values (mean +/- SD) at the end of therapy and at 14 and 33 days after chelation were significantly lower than pretreatment in both groups (BAL + EDTA: 17 +/- 10, 34 +/- 7, 36 +/- 11 vs 58 +/- 14 micrograms/dl, p < 0.02, 0.01, 0.001, respectively; DMSA + EDTA: 10 +/- 4, 30 +/- 10, 30 +/- 14 vs 50 +/- 10 micrograms/dl, p < 0.01, 0.001, 0.01, respectively). The percentage reduction (mean +/- SD) in BPb from pretreatment at the end of therapy and on days 14 and 33 after chelation did not differ between the groups (BAL + EDTA: -71.2% +/- 19.8%, -40.2% +/- 13.8%, -37.1% +/- 17%; DMSA + EDTA: -79.9% +/- 8.7%, -38.3% +/- 21.6%, -37% +/- 32%; p > 0.20). Elevation of alanine aminotransferase and vomiting during therapy were observed more frequently in the BAL + EDTA group compared with the DMSA + EDTA group. Treatment with DMSA or BAL combined with EDTA results in a comparable reduction in BPb.

  4. Effects of disodium EDTA and calcium infusion on prolactin and thyrotropin responses to thyrotropin-releasing hormone in healthy man.

    PubMed

    Dudczak, R; Waldhäusl, W K; Bratusch-Marrain, P

    1983-03-01

    To determine the impact of induced hypo- and hypercalcemia on TRH (400 micrograms)-stimulated TSH and PRL release, healthy subjects (n = 11) were infused with 5% glucose in water (n = 11), disodium EDTA (n = 11), or calcium gluconate (n = 7). TRH was given as an iv bolus 60 min (5% glucose and EDTA) and 120 min (calcium) after initiation of the respective infusion. Basal plasma concentrations of TSH remained unchanged during induced hypo- and hypercalcemia, whereas those of PRL fell during the latter (P less than 0.05). The mean sum of increments (0-90 min) in PRL and TSH was considerably greater during hypocalcemia than during hypercalcemia (PRL, P less than 0.002; TSH, P less than 0.005). The increments in the plasma hormone concentration above basal after iv TRH were increased compared to those in normocalcemia (PRL, 98.4 +/- 37.9 ng/ml; TSH, 38.9 +/- 11.8 microU/ml) during hypocalcemia [PRL, 128 +/- 47.8 ng/ml (P less than 0.002); TSH, 46.7 +/- 12.8 microU/ml; (P less than 0.005)], but were impaired during hypercalcemia [PRL, 70.1 +/- 27 ng/ml (P less than 0.002); TSH, 28.9 +/- 8.5 microU/ml (P less than 0.025)]. The mean sum of increments in PRL was related to concentrations of both serum calcium (r = -0.59; P less than 0.01) and PTH (r = 0.51; P less than 0.05). A relation was also seen between the incremental responses of TSH and serum calcium (r = -0.52; P less than 0.05), PTH (r = 0.55; P less than 0.01), and phosphorus (r = -0.55; P less than 0.01). We conclude that in healthy man, TRH-mediated release of both PRL and TSH are inversely related to serum calcium concentrations in such a manner that hormone secretion is enhanced by acute hypocalcemia, but blunted by hypercalcemia.

  5. 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).

  6. Effects of Glycyrrhetinic Acid on GSH Synthesis Induced by Realgar in the Mouse Hippocampus: Involvement of System [Formula: see text], System [Formula: see text], MRP-1, and Nrf2.

    PubMed

    Wang, Yan-Lei; Chen, Mo; Huo, Tao-Guang; Zhang, Ying-Hua; Fang, Ying; Feng, Cong; Wang, Shou-Yun; Jiang, Hong

    2016-04-02

    Realgar, a type of mineral drug-containing arsenic, exhibits neurotoxicity. Brain glutathione (GSH) is crucial to protect the nervous system and to resist arsenic toxicity. Therefore, the main aim of this study was to explore the neurotoxic mechanisms of realgar and the protective effects of glycyrrhetinic acid (GA) by observing the effects of GA on the hippocampal GSH biosynthetic pathway after exposure to realgar. Institute of Cancer Research (ICR) mice were randomly divided into five groups: a control group, a GA control group, a realgar alone group, a low-dose GA intervention group, and a high-dose GA intervention group. Cognitive ability was tested using an object recognition task (ORT). The ultrastructures of the hippocampal neurons and synapses were observed. mRNA and protein levels of EAAT1, EAAT2, EAAT3, xCT, Nrf2, HO-1, γ-GCS (GCLC, GCLM), and MRP-1 were measured, as was the cellular localization of EAAT3, xCT, MRP-1, and Nrf2. The levels of GSH in the hippocampus, the levels of glutamate (Glu) and cysteine (Cys) in the extracellular fluid of hippocampal CA1 region, and the levels of active sulfur in the brain were also investigated. The results indicate that realgar lowered hippocampal GSH levels, resulting in ultrastructural changes in hippocampal neurons and synapses and deficiencies in cognitive ability, ultimately inducing neurotoxicity. GA could trigger the expression of Nrf2, HO-1, EAAT1, EAAT2, EAAT3, xCT, MRP-1, GCLC, and GCLM. Additionally, the expression of γ-GT and the supply levels of Glu and Cys increased, ultimately causing a significant increase in hippocampal GSH to alleviate realgar-induced neurotoxicity. In conclusion, the findings from our study indicate that GA can antagonize decreased brain GSH levels induced by realgar and can lessen the neurotoxicity of realgar.

  7. Glycyrrhizic acid and 18β-glycyrrhetinic acid modulate lipopolysaccharide-induced inflammatory response by suppression of NF-κB through PI3K p110δ and p110γ inhibitions.

    PubMed

    Wang, Chung-Yi; Kao, Tzu-Chien; Lo, Wen-Hsieh; Yen, Gow-Chin

    2011-07-27

    The roots and rhizomes of licorice ( Glycyrrhia ) species have been used extensively as natural sweeteners and herbal medicines. The aim of this work was to determine the in vitro anti-inflammatory effects of glycyrrhizic acid (GA) and 18β-glycyrrhetinic acid (18βGA) from licorice in a lipopolysaccharide (LPS)-stimulated macrophage model. The results showed that treatment with 25-75 μM GA or 18βGA did not reduce RAW 264.7 cell viability but did significantly inhibit the production of LPS-induced nitric oxide (NO), prostaglandin E(2) (PGE(2)), and intracellular reactive oxygen species (ROS). Western blotting and reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that GA and 18βGA significantly reduced the protein and mRNA levels of iNOS and COX-2 in LPS-induced macrophages. Both GA and 18βGA inhibited the activation of NF-κB and the activities of phosphoinositide-3-kinase (PI3K) p110δ and p110γ isoforms and then reduced the production of LPS-induced tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in a dose-dependent manner. In conclusion, these results indicate that GA and 18βGA may provide an anti-inflammatory effect by attenuating the generation of excessive NO, PGE(2), and ROS and by suppressing the expression of pro-inflammatory genes through the inhibition of NF-κB and PI3K activity. Thus, the results suggest that GA and 18βGA might serve as potential agents for the treatment of inflammatory-mediated diseases.

  8. Inhibition of protein kinase C α/βII and activation of c-Jun NH2-terminal kinase mediate glycyrrhetinic acid induced apoptosis in non-small cell lung cancer NCI-H460 cells.

    PubMed

    Song, Junho; Ko, Hyun-suk; Sohn, Eun Jung; Kim, Bonglee; Kim, Jung Hyo; Kim, Hee Jeong; Kim, Chulwoo; Kim, Jai-eun; Kim, Sung-Hoon

    2014-02-15

    Though glycyrrhetinic acid (GA) from Glycyrrhiza glabra was known to exert antioxidant, antifilarial, hepatoprotective, anti-inflammatory and anti-tumor effects, the antitumor mechanism of GA was not clearly elucidated in non-small cell lung cancer cells (NSCLCCs). Thus, in the present study, the underlying apoptotic mechanism of GA was examined in NCI-H460 NSCLCCs. GA significantly suppressed the viability of NCI-H460 and A549 non-small lung cancer cells. Also, GA significantly increased the sub G1 population by cell cycle analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells in a concentration dependent manner in NCI-H460 non-small lung cancer cells. Consistently, GA cleaved poly (ADP-ribosyl) polymerase (PARP), caspase 9/3, attenuated the expression of Bcl-XL, Bcl-2, Cyclin D1 and Cyclin E in NCI-H460 cells. Interestingly, GA attenuated the phosphorylation of protein kinase C (PKC) α/βII and extracellular activated protein kinase (ERK) as well as activated the phosphorylation of PKC δ and c-Jun NH2-terminal kinase in NCI-H460 cells. Conversely, PKC promoter phorbol 12-myristate 13-acetate (PMA) and JNK inhibitor SP600125 reversed the cleavages of caspase 3 and PARP induced by GA in NCI-H460 cells. Overall, our findings suggest that GA induces apoptosis via inhibition of PKC α/βII and activation of JNK in NCI-H460 non-small lung cancer cells as a potent anticancer candidate for lung cancer treatment.

  9. Glycyrrhetinic acid attenuates lipopolysaccharide-induced fulminant hepatic failure in d-galactosamine-sensitized mice by up-regulating expression of interleukin-1 receptor-associated kinase-M.

    PubMed

    Yin, Xinru; Gong, Xia; Zhang, Li; Jiang, Rong; Kuang, Ge; Wang, Bin; Chen, Xinyu; Wan, Jingyuan

    2017-04-01

    Glycyrrhetinic acid (GA), the main active ingredient of licorice, reportedly has anti-inflammatory and hepatoprotective properties, but its molecular mechanisms remain be elusive. In the present study, Balb/c mice were pretreated with GA (10, 30, or 100mg/kg) 1h before lipopolysaccharide (LPS)/d-galactosamine (D-GalN) administration. In other in vitro experiment, RAW264.7 macrophages were pretreated with GA before LPS exposure. The mortality, hepatic tissue histology, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed. Toll like receptor 4 (TLR4), interleukin-1 receptor-associated kinases (IRAKs), activation of mitogen-activated protein kinases (MAPKs) and NF-κB, and production of TNF-α were assessed by flow cytometry, western blotting, and enzyme-linked immunosorbent assay (ELISA), respectively. Our results showed that pretreatment with GA protected mice against LPS/D-GalN-induced fulminant hepatic failure (FHF), including a dose-dependent alleviation of mortality and ALT/AST elevation, ameliorating hepatic pathological damage, and decreasing TNF-α release. Moreover, GA inhibited LPS-induced activation of MAPKs and NF-κB in response to LPS, but the expression of TLR4 was not affected in vivo and in vitro. Notably, GA pretreatment in vivo suppressed IRAK-1 activity while inducing IRAK-M expression. Silencing of IRAK-M expression with siRNA blocked these beneficial effects of GA on the activation of MAPKs and NF-κB as well as TNF-α production in LPS-primed macrophages. Taken together, we conclude that GA could prevent LPS/D-GalN-induced FHF. The underlying mechanisms may be related to up-regulation of IRAK-M, which in turn caused deactivation of IRAK-1 and subsequent MAPKs and NF-κB, resulting in inhibiting TNF-α production.

  10. Anti-inflammatory and hepatoprotective effects of glycyrrhetinic acid on CCl4-induced damage in precision-cut liver slices from Jian carp (Cyprinus carpio var. jian) through inhibition of the nf-kƁ pathway.

    PubMed

    Cao, Liping; Ding, Weidong; Jia, Rui; Du, Jingliang; Wang, Tao; Zhang, Chunyun; Gu, Zhengyan; Yin, Guojun

    2017-03-10

    In order to evaluate the antioxidant and anti-inflammatory effects of glycyrrhetinic acid (GA) on carbon tetrachloride (CCl4)-induced damage in precision-cut liver slices (PCLS) from Jian carp (Cyprinus carpio. Jian), an acute liver damage model was established in this study. The viability of PCLS, levels of anti-oxidases in liver homogenates, expression of inflammation-related genes including nuclear factor-κB (nf-κB)/c-rel, inducible nitric oxide synthase (inos), interleukin-1β (il-1β), interleukin-6 (il-6) and interleukin-8 (il-8), and protein levels of (nf-κB)/c-rel in liver tissues were measured. The results showed that pretreatment of PCLS with GA at 5 and 10 μg/mL for 6 h significantly inhibited the cytotoxicity of CCl4. GA attenuated CCl4-induced oxidative stress in PCLS through promoting the recovery of superoxide dismutase (SOD) and glutathione (GSH) levels, and inhibiting malondialdehyde (MDA) synthesis. In inflammatory response, GA at both 5 and 10 μg/mL significantly inhibited the increase in mRNA levels of inflammatory cytokines including nf-kƁ/c-rel, inos, il-1β, il-6 and il-8, and the protein level of Nf-kƁ/C-rel induced by CCl4. Furthermore, treatment with pyrrolyl dithiocarbamate (PDTC, 4 μg/mL), an inhibitor of nuclear transcription factor nf-kB, significantly inhibited nf-kB levels, and transcription of downstream cytokines inos, il-1β, il-6 and il-8, also the viability of PCLS was significantly increased. These results indicated that GA suppressed inflammation and reduced cytotoxicity by inhibiting the nf-kƁ signaling pathway, and plays a role in liver protection.

  11. Anaphylaxis to disodium cromoglycate.

    PubMed

    Ibañez, M D; Laso, M T; Martinez-San Irineo, M; Alonso, E

    1996-09-01

    Reports about side effects from cromolyn sodium (DSCG) are few and only a minority of them indicate the possibility of an immediate type I hypersensitivity reaction. We report an 8-year-old boy with a history of seasonal rhinoconjunctivitis and asthma. The patient reported two immediate episodes of acute asthma following inhalation of a cromolyn sodium (DSCG) capsule with an interval of 6 months. The latter occasion was also associated with conjunctivitis and generalized urticaria, requiring emergency treatment. An end-point prick test elicited a 4-mm wheal at 10 mg/mL with DSCG solution for inhalation and DSCG eye drops. An end-point intradermal skin test with DSCG solution for inhalation elicited a 12-mm mean diameter wheal at 10 mg/mL. During the intradermal test, the patient developed conjunctivitis and wheezing with a FEV1 fall of 27% from baseline. Controlled conjunctival and bronchial challenge tests were positive. The bronchial challenge test was repeated 3 years later showing a FEV1 fall of 22% five minutes after inhalation of 1 mg/mL DSCG during one minute. A leukocyte histamine release test performed by an autoanalysis fluorometric procedure, with several dilutions of DSCG, was negative. This case of DSCG anaphylaxis satisfies the criteria for an IgE-mediated reaction. We believe that thought should be given more frequently to this mechanism when patients report adverse reactions to DSCG.

  12. 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

  13. A comparison of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning.

    PubMed

    Bradberry, Sally; Vale, Allister

    2009-11-01

    This article reviews the experimental and clinical studies that have compared the efficacy (impact on urine lead excretion, blood and tissue lead concentrations, resolution of features and survival) of sodium calcium edetate (edetate calcium disodium) and succimer (DMSA) in the treatment of inorganic lead poisoning. It also summarizes the pharmacokinetic and pharmacodynamic aspects and the adverse effects of treatment. Medline, Toxline, and Embase were searched for all available years to June 2009. PHARMACOKINETICS AND PHARMACODYNAMICS: The absorption of oral DMSA is more complete than sodium calcium edetate; the latter has to be administered parenterally. Both antidotes are distributed predominantly extracellularly. Sodium calcium edetate is not metabolized, whereas DMSA is extensively metabolized to mixed disulfides of cysteine. The two antidotes have elimination half-lives of less than 60 min. There is no evidence that either antidote crosses the blood-brain barrier to any major extent. Sodium calcium edetate chelates lead by displacement of the central Ca2+ ion with Pb2+. The nature of the DMSA-lead chelate is less clearly defined. There is evidence that the mixed disulfides of cysteine are the active chelating moiety in humans. If this is the case, this suggests that chelation occurs principally, if not exclusively, in the kidney. The primary source of lead mobilized by sodium calcium edetate is bone with an additional contribution from kidney and liver. Comparison of the experimental studies is complicated by substantial variations in study design, particularly the antidote dose, the route and duration of treatment, the amount and duration of lead dosing, and lack of direct comparison between antidotes (comparison was usually made with control). In experimental studies that used equimolar and clinically relevant antidote doses and assessed the impact of DMSA and sodium calcium edetate on urine lead excretion and/or blood lead concentrations, similar results

  14. Prevention of mast cell degranulation by disodium cromoglycate attenuates the development of hypoxic pulmonary hypertension in rats exposed to chronic hypoxia.

    PubMed

    Banasová, Alena; Maxová, Hana; Hampl, Václav; Vízek, Martin; Povýsilová, Viera; Novotná, Jana; Vajnerová, Olga; Hnilicková, Olga; Herget, Jan

    2008-01-01

    Chronic hypoxia induces lung vascular remodeling, which results in pulmonary hypertension. Vascular remodeling is associated with collagenolysis and activation of matrix metalloproteinases (MMPs). One of the possible sources of MMPs in hypoxic lung are mast cells. The role of lung mast cell collagenolytic activity in hypoxic pulmonary hypertension was tested by the inhibitor of mast cell degranulation disodium cromoglycate (DSCG). Rats were treated with DSCG in an early or later phase of isobaric hypoxia. Control groups were exposed to hypoxia only or to normoxia. Lung hemodynamics, muscularization and collagen metabolism in the walls of peripheral pulmonary vessels in the lungs were measured. DSCG applied at an early phase of exposure to hypoxia reduced the development of pulmonary hypertension, inhibited muscularization in peripheral pulmonary arteries and decreased the amount of collagen cleavage fragments in prealveolar vessels. Mast cell degranulation plays a role in the initiation of hypoxic pulmonary vascular remodeling. 2008 S. Karger AG, Basel.

  15. Comparative effectiveness of Tiron (4,5-dihydroxy benzene 1,3-disulphonic acid disodium salt) and CaNa2EDTA with time after beryllium poisoning.

    PubMed

    Sharma, P; Shukla, S

    2000-08-01

    The efficacy of two chelating agents (Tiron and calcium disodium EDTA) in the treatment of beryllium induced blood biochemistry and hepatic histopathological alteration was investigated at different duration in female albino rats. Single administration of beryllium nitrate at a dose of 50 mg/kg (im) showed significant decrease in haemoglobin percentage, blood sugar level, protein contents and activity of alkaline phosphatase. On the contrary significant elevation was found in the activity of transaminases (AST and ALT). Tiron was found to be more effective than CaNa2EDTA in reducing the beryllium induced haematological alterations and histopathological lesions in liver. These findings were further confirmed by AAS thus, in which reduced beryllium body burden was seen in liver and blood with Tiron.

  16. Therapeutic efficacy of combined meso 2,3-dimercaptosuccinic acid and calcium disodium edetate treatment during acute lead intoxication in rats.

    PubMed

    Flora, G J; Seth, P K; Prakash, A O; Mathur, R

    1995-05-01

    1. The therapeutic ability of Ca disodium EDTA and meso 2,3-dimercaptosuccinic acid (DMSA) was studied, both individually and when given in combination, in reducing lead concentration in blood and other soft tissues, and in restoring lead induced altered biochemical variables in acute lead intoxicated rats. 2. Combined treatment with the above two chelating agents was more beneficial in reducing blood and hepatic lead compared to treatment with these drugs alone. Kidney lead concentration however, remained high following combined treatment, indicating the possibility of extra renal burden following treatment. 3. Lead sensitive biochemical variables also responded more favourably to combined treatment than treatment with these drugs alone. However, clinical biochemical indices indicate caution regarding the use of this new treatment regimen, and further investigation is required.

  17. 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.

  18. Experimental and computational evidence for alpha-lactone intermediates in the addition of aqueous bromine to disodium dimethyl-maleate and -fumarate.

    PubMed

    Pirinççioğlu, Necmettin; Robinson, James J; Mahon, Mary F; Buchanan, J Grant; Williams, Ian H

    2007-12-21

    Structural analysis of the bromo-beta-lactones obtained by addition of bromine to aqueous solutions of disodium 2,3-dimethylmaleate and 2,3-dimethylfumarate reveals stereochemistries opposite to those originally assigned in 1937: cis alkene yields erythro lactone, and trans alkene yields threo lactone. B3LYP/6-31+G(d) calculations using a PCM description of aqueous solvation confirm the validity of our proposed mechanism, in which the first-formed intermediate in each case is an alpha-lactone. The cyclic bromonium species is not an intermediate. An alternative pathway leading directly from cis alkene to cis lactone, via an unusual frontside displacement mechanism, is over 20 kJ mol(-1) higher in free energy. Hydrolysis of the bromo-beta-lactones yields bromohydrins whose stereochemistries as determined by X-ray crystallography indicate stereospecific formation by acyl-oxygen cleavage of the lactone ring, again contrary to the original view.

  19. Crystal structure of disodium 2-amino-6-oxo-6,7-di-hydro-1H-purine-1,7-diide hepta-hydrate.

    PubMed

    Gur, Dvir; Shimon, Linda J W

    2015-03-01

    In the title compound, disodium 2-amino-6-oxo-6,7-di-hydro-1H-purine-1,7-diide hepta-hydrate, 2Na(+)·C5H3N5O(2-)·7H2O, the structure is composed of alternating (100) layers of guanine mol-ecules and hydrated Na(+) ions. Within the guanine layer, the mol-ecules are arranged in centrosymmetric pairs, with a partial overlap between the guanine rings. In this compound, guanine exists as the amino-keto tautomer from which deprotonation from N1 and N7 has occurred (purine numbering). There are no direct inter-actions between the Na(+) cations and the guanine anions. Guanine mol-ecules are linked to neighboring water mol-ecules by O-H⋯N and O-H⋯O hydrogen bonds into a network structure.

  20. Comparison of hepatocellular carcinoma conspicuity on hepatobiliary phase images with gadoxetate disodium vs. delayed phase images with extracellular cellular contrast agent.

    PubMed

    Kim, So Yeon; Wu, En-Haw; Park, Seong Ho; Wang, Z Jane; Hope, Thomas A; Yee, Judy; Zhao, Li-Qin; Chang, Wei-Chou; Yeh, Benjamin M

    2016-08-01

    To compare the conspicuity of hepatocellular carcinoma (HCC) on hepatobiliary phase of gadoxetate disodium-enhanced vs. delayed phase of gadodiamide-enhanced MR images, relative to liver function. We retrospectively identified 86 patients with newly diagnosed HCC between 2010 and 2013 and recorded the severity of liver disease by Child-Pugh class (CPC). 38 patients had gadodiamide-enhanced 5-min delayed and 48 had gadoxetate disodium-enhanced 20-min delayed hepatobiliary MR images. The conspicuity of 86 HCCs (mean size, 2.7 cm) was graded visually on a 3-point scale and quantified by liver-to-tumor contrast ratios (LTC). The relative liver parenchymal enhancement (RPE) was measured. For different CPCs, we compared the conspicuity of HCC and RPE between gadodiamide and gadoxetate. In patients with CPC A, the visual conspicuity and LTC of the 27 HCCs imaged with gadodiamide were significantly lower than those of the 38 HCCs with gadoxetate (P < 0.01, <0.01, respectively). RPE was lower in gadodiamide scans than gadoxetate scans (P < 0.01). Conversely, in patients with CPC B and C, HCCs appeared more frequently as definite hypointensity when imaged with gadodiamide (72.7%, 8/11) than gadoxetate (20%, 2/10, P = 0.03). LTC (mean 18.1 vs. 7.5, P = 0.04) and RPE (mean 75.5 vs. 45.4, P = 0.04) was significantly higher in the gadodiamide than gadoxetate scans. In patients with compromised liver function, hypointensity of HCC is more conspicuous in the gadodiamide delayed phase than the gadoxetate hepatobiliary phase. This likely reflects the high extracellular accumulation of gadodiamide and poor hepatocyte uptake of gadoxetate in patients with compromised liver function.

  1. Systemic mastocytosis with KIT V560G mutation presenting as recurrent episodes of vascular collapse: response to disodium cromoglycate and disease outcome.

    PubMed

    Conde-Fernandes, Iolanda; Sampaio, Rita; Moreno, Filipa; Palla-Garcia, José; Teixeira, Maria Dos Anjos; Freitas, Inês; Neves, Esmeralda; Jara-Acevedo, Maria; Escribano, Luis; Lima, Margarida

    2017-01-01

    Mastocytosis are rare diseases characterized by an accumulation of clonal mast cells (MCs) in one or multiple organs or tissues. Patients with systemic mastocytosis (SM), whose MCs frequently arbor the activating D816V KIT mutation, may have indolent to aggressive diseases, and they may experience MC mediator related symptoms. Indolent SM with recurrent anaphylaxis or vascular collapse in the absence of skin lesions, ISMs(-), is a specific subtype indolent SM (ISM), and this clonal MC activation disorder represents a significant fraction of all MC activation syndromes. The V560G KIT mutation is extremely rare in patients with SM and its biological and prognostic impact remains unknown. A 15-year old boy was referred to our hospital because of repeated episodes of flushing, hypotension and syncope since the age of 3-years, preceded by skin lesions compatible with mastocytosis on histopathology that had disappeared in the late-early childhood. Diagnosis of ISM, more precisely the ISMs(-) variant, was confirmed based on the clinical manifestations together with increased baseline serum tryptase levels and the presence of morphologically atypical, mature appearing (CD117+high, FcεRI+) phenotypically aberrant (CD2+, CD25+) MCs, expressing activation-associated markers (CD63, CD69), in the bone marrow. Molecular genetic studies revealed the presence of the KIT V560G mutation in bone marrow MCs, but not in other bone marrow cells, whereas the screening for mutations in codon 816 of KIT was negative. The patient was treated with oral disodium cromoglycate and the disease had a favorable outcome after an eleven-year follow-up period, during which progressively lower serum tryptase levels together with the fully disappearance of all clinical manifestations was observed. To the best of our knowledge this first report of a patient with ISM, whose bone marrow MCs carry the KIT V560G activating mutation, manifesting as recurrent spontaneous episodes of flushing and vascular

  2. A Validated Reverse Phase HPLC Method for the Determination of Disodium EDTA in Meropenem Drug Substance with UV-Detection using Precolumn Derivatization Technique

    PubMed Central

    Narola, Bhavil; Singh, A.S.; Mitra, M.; Santhakumar, P.R.; Chandrashekhar, T.G.

    2011-01-01

    This paper deals with development and validation of a high performance liquid chromatographic method for the quantitative determination of disodium EDTA (Ethylenediaminetetraacetic acid) in Meropenem active pharmaceutical ingredient (API). EDTA was derivatized with Ferric chloride solution by heating at 70 °C in water bath for about 20 minutes and the chromatographic separation achieved by injecting 100 μL of the derivatized mixture into a Waters HPLC system with photodiode array detector using a Phenomenex Luna C18(2) column (250 × 4.6 mm), 5 μ. The mobile phase consisting of 5% methanol and 95% of 0.7 g/L solution of Tetra butyl ammonium bromide and 4.6 g/L solution of sodium acetate trihydrate in water (pH adjusted to 4.0 with the help of acetic acid glacial) and a flow rate of 1 milliliter/minute. EDTA eluted at approximately 6 minutes. The method was suitably validated with respect to specificity, linearity of response, precision, accuracy, ruggedness, stability in analytical solution, limit of quantitation and detection and robustness for its intended use. PMID:21760705

  3. 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

  4. Downregulation of mucosal mast cell activation and immune response in diarrhoea-irritable bowel syndrome by oral disodium cromoglycate: A pilot study

    PubMed Central

    Lobo, Beatriz; Ramos, Laura; Martínez, Cristina; Guilarte, Mar; González-Castro, Ana M; Alonso-Cotoner, Carmen; Pigrau, Marc; de Torres, Inés; Rodiño-Janeiro, Bruno K; Salvo-Romero, Eloisa; Fortea, Marina; Pardo-Camacho, Cristina; Guagnozzi, Danila; Azpiroz, Fernando

    2017-01-01

    Background and goal Diarrhoea-predominant irritable bowel syndrome (IBS-D) exhibits intestinal innate immune and mucosal mast cell (MC) activation. MC stabilisers have been shown to improve IBS symptoms but the mechanism is unclear. Our primary aim was to investigate the effect of oral disodium cromoglycate (DSCG) on jejunal MC activation and specific innate immune signalling pathways in IBS-D, and secondarily, its potential clinical benefit. Study Mucosal MC activation (by ultrastructural changes, tryptase release and gene expression) and innate immune signalling (by protein and gene expression) were quantified in jejunal biopsies from healthy (HS; n = 16) and IBS-D subjects after six months of either treatment with DSCG (600 mg/day, IBS-D-DSCG group; n = 18) or without treatment (IBS-D-NT group; n = 25). All IBS-D patients recorded abdominal pain and bowel habits at baseline and in the last 10 days prior to jejunal sampling. Results IBS-D-NT exhibited significant MC activation and over-expression of immune-related genes as compared to HS, whereas in IBS-D-DSCG MC activity and gene expression were similar to HS. Furthermore, DSCG significantly reduced abdominal pain and improved stool consistency. Conclusion Oral DSCG modulates mucosal immune activity and improves gut symptoms in IBS-D patients. Future placebo-controlled clinical trials are needed for confirmation of clinical benefit of DSCG for IBS-D.

  5. 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.

  6. Effect of disodium cromoglycate on airway mucus secretion during antigen-induced late asthmatic responses in a murine model of asthma.

    PubMed

    Koyama, Harumi; Tokuyama, Kenichi; Nishimura, Hideko; Mizuno, Takahisa; Mayuzumi, Hiroo; Ohki, Yasushi; Arakawa, Hirokazu; Mochizuki, Hiroyuki; Morikawa, Akihiro

    2005-11-01

    Disodium cromoglycate (DSCG) is known to inhibit both immediate and late asthmatic responses (IAR and LAR). However, its effect on mucus hypersecretion is unknown. Using a murine model of asthma, we aimed to determine whether mucus secretion increased during IAR and LAR. We also studied the potency of DSCG in inhibiting mucus secretion and on airway eosinophilia. Mice were subjected to initial intraperitoneal sensitization and airway challenge to ovalbumin (OVA) and then provoked by additional exposure to OVA. Some mice were pretreated with aerosolized DSCG (20 mg/ml) 1 h before the provocation with OVA. After serial measurements of enhanced pause (Penh), an indicator of airflow obstruction, serum samples and bronchoalveolar lavage fluids (BALF) were collected. Then, the lungs were excised and a morphometric analysis for mucus hypersecretion was performed. A biphasic increase in Penh (IAR and LAR) was observed in sensitized animals after provocation with OVA. Airway eosinophilia was observed during both responses. Intraluminal mucus significantly increased during LAR, but not during IAR. DSCG significantly attenuated both IAR and LAR, and significantly inhibited the increase in intraluminal mucus during LAR, but had no effect on eosinophilia in BALF. Our results suggest that airway hypersecretion may be involved as a component of airflow obstruction during LAR, and that this is unlikely during IAR. DSCG may be effective in reducing excessive airway mucus caused by exposure to allergens. Copyright (c) 2005 S. Karger AG, Basel.

  7. 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. Copyright © 2014 John Wiley & Sons, Ltd.

  8. Taurine suppresses osteoblastic differentiation of aortic valve interstitial cells induced by beta-glycerophosphate disodium, dexamethasone and ascorbic acid via the ERK pathway.

    PubMed

    Feng, Xiang; Li, Jian-ming; Liao, Xiao-bo; Hu, Ye-rong; Shang, Bao-peng; Zhang, Zhi-yuan; Yuan, Ling-qing; Xie, Hui; Sheng, Zhi-feng; Tang, Hao; Zhang, Wei; Gu, Lu; Zhou, Xin-min

    2012-10-01

    Aortic valve calcification (AVC) is an active process characterized by osteoblastic differentiation of the aortic valve interstitial cells (AVICs). Taurine is a free β-amino acid and plays important physiological roles including protective effect of cardiovascular events. To evaluate the possible role of taurine in AVC, we isolated human AVICs from patients with type A dissection without leaflet disease. We demonstrated that the cultured AVICs express SM α-actin, vimentin and taurine transporter (TAUT), but not CD31, SM-myosin or desmin. We also established the osteoblastic differentiation model of the AVICs induced by pro-calcific medium (PCM) containing β-glycerophosphate disodium, dexamethasone and ascorbic acid in vitro. The results showed that taurine attenuated the PCM-induced osteoblastic differentiation of AVICs by decreasing the alkaline phosphate (ALP) activity/expression and the expression of the core binding factor α1 (Cbfα1) in a dose-dependent manner (reaching the maximum protective effect at 10 mM), and taurine (10 mM) inhibited the mineralization level of AVICs in the form of calcium content significantly. Furthermore, taurine activated the extracellular signal-regulated protein kinase (ERK) pathway via TAUT, and the inhibitor of ERK (PD98059) abolished the effect of taurine on both ALP activity/expression and Cbfα1 expression. These results suggested that taurine could inhibit osteoblastic differentiation of AVIC via the ERK pathway.

  9. 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.

  10. 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

  11. 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.

  12. Calcium disodium ethylenediaminetetraacetate-chelated lead as a predictor for subclinical lead neurotoxicity: follow-up study on gun-metal foundry workers.

    PubMed

    Yokoyama, K; Araki, S; Aono, H; Murata, K

    1998-10-01

    To examine if chelated lead was a more predictive indicator of the subclinical effect of lead on conduction velocities of faster or slower nerve fibers as compared with blood lead (BPb). Distribution of conduction velocities (DCV) in large myelinated fibers of the sensory median nerve was measured twice at a 1-year interval in 17 male gun-metal foundry workers with BPb concentrations of 22-59 (mean 40.2) microg/dl and a mobilization yield of lead into urine (MPb) by calcium disodium ethylenediaminetetraacetate of 0.15-2.09 (mean 1.19) mg/24 h for the 1st year and in 20 healthy males (controls). Yearly changes in the conduction velocities of faster fibers were significantly correlated with the corresponding change in MPb (P < 0.05) but not with that in BPb (P > 0.05). In ten workers showing an increase in MPb during the 1-year period (0.44 mg/24 h on average) the conduction velocities of faster fibers were decreased significantly, resulting in the values being significantly lower in all the workers combined than in the controls (P < 0.05). On the other hand, in the remaining workers, who showed a lesser extent of reduction in MPb (0.08 mg/24 h on average), the DCV did not change (P > 0.05). Chelated lead might be a more predictive indicator of the effect of lead on the conduction velocities of faster fibers than blood lead.

  13. Combined therapeutic potential of meso-2,3-dimercaptosuccinic acid and calcium disodium edetate on the mobilization and distribution of lead in experimental lead intoxication in rats.

    PubMed

    Flora, S J; Bhattacharya, R; Vijayaraghavan, R

    1995-05-01

    Asymptomatic lead poisoning remains a serious public health problem in developed and developing countries. Chelation therapy particularly with calcium disodium ethelenediamine tetracetic acid (CaNa2EDTA) is often used therapeutically to reduce the body burden of lead. This chelating drug has serious side effects and drawbacks primarily related to redistribution of lead, nephrotoxicity, and essential metal depletion. The present study was planned to determine the effectiveness of CaNa2EDTA and meso-2,3-dimercaptosuccinic acid (DMSA) used in combination. Both drugs, when administered individually, resulted in significant urinary excretion of lead and lowered the tissue lead burden. Combined treatment with CaNa2EDTA and DMSA elicits an additive response in promoting urinary lead elimination, depleting body lead burden, and restoring altered lead-sensitive biochemical variables. Further, no redistribution of lead to brain or any other soft organ following combined DMSA-CaNa2EDTA treatment was observed indicating a definite advantage of combined therapy over the conventional treatment with CaNa2EDTA or DMSA alone. However, an elevation of serum transaminase activity, creatinine level, and depletion of blood zinc level may limit the usefulness of this combined treatment.

  14. Effects of calcium disodium EDTA and meso-2,3-dimercaptosuccinic acid on tissue concentrations of lead for use in treatment of calves with experimentally induced lead toxicosis.

    PubMed

    Meldrum, James B; Ko, Kam W

    2003-06-01

    To compare the efficacy of calcium disodium EDTA (CaNa2EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) in reducing concentrations of lead in selected tissues for use in treatment of calves with experimentally induced lead toxicosis. 19 sexually intact male Holstein calves that weighed 35 to 60 kg. Calves were randomly assigned to 1 of 5 treatment groups: group 1, control calves; group 2, lead only; group 3, lead and EDTA; group 4, lead and DMSA; and group 5, lead, EDTA, and DMSA. Calves in groups 2 to 5 were dosed daily with lead (5 mg/kg, PO) for 10 days. Doses of EDTA (100 mg/kg) and DMSA (25 mg/kg) were administered IV once daily for 4 consecutive days beginning on day 11. Effects of the chelators on lead concentrations in the liver, kidneys, testes, muscles, bones, and brain were compared among the various groups. Compared with the effects of EDTA, DMSA greatly reduced lead concentrations in renal and hepatic tissues. We did not detect significant differences for the effects of EDTA or DMSA on lead concentrations in the testes; there was an adverse interaction of EDTA with DMSA that caused an increase in lead concentrations in the testes. DMSA is much more effective than EDTA in removing lead from renal and hepatic tissues in calves. Use of DMSA in calves with lead intoxication appears to be a viable treatment option. Combining DMSA and EDTA as a treatment modality in calves did not offer any advantages.

  15. Effect of a novel ascorbic derivative, disodium isostearyl 2-O-L-ascorbyl phosphate, on normal human dermal fibroblasts against reactive oxygen species.

    PubMed

    Shibayama, Hiroharu; Hisama, Masayoshi; Matsuda, Sanae; Kawase, Atsushi; Ohtsuki, Mamitaro; Hanada, Katsumi; Iwaki, Masahiro

    2008-04-01

    The novel amphiphilic vitamin C derivative disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na), which has a C(18) alkyl chain attached to the stable ascorbate derivative sodium L-ascorbic acid 2-phosphate (VCP-Na), was evaluated for reduction of cell damage induced by oxidative stress, ultraviolet A (UVA), ultraviolet B (UVB), and H(2)O(2); stimulation of collagen synthesis against UVA irradiation; and inhibition of matrix metalloproteinase-1 (MMP-1) activity induced by UVA in human normal dermal fibroblasts. VCP-IS-2Na pretreatment resulted in significant protection against cell damage induced by UVB, UVA, and H(2)O(2). The amount of type I collagen following UVA irradiation was increased by treatment with VCP-IS-2Na in a concentration-dependent manner. These effects of VCP-IS-2Na were superior to those of L-ascorbic acid (vitamin C, VC) and VCP-Na. On the other hand, VCP-IS-2Na suppressed 65% of the excess MMP-1 irradiated UVA, and VC and VCP-Na slightly suppressed it.

  16. 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.

  17. [The effect of disodium cromoglycate (DSCG) on infiltration of inflammatory cells into bronchial mucosa and on expression of adhesion molecules in asthmatics].

    PubMed

    Hoshino, M; Nakamura, Y

    1995-06-01

    We studied the effect of disodium cromoglycate (DSCG) used as a therapeutic drug for the treatment of bronchial asthma on infiltration of inflammatory cells into the bronchial mucosa and on the expression of adhesion molecules in asthmatic patients. Biopsies of the bronchial mucosa of 9 patients with atopic asthma were performed before and after the administration of an aerosol containing DSCG (8 mg/day). Staining with anti-EG2 antibody was made on the tissues obtained to determine the number of eosinophils, with anti-NP57 antibody to determine the number of neutrophils, with anti-AA1 antibody for mast cells, with anti-CD4, -CD8, -CD3 for T lymphocytes, and with anti-CD68 antibody for macrophages. Another staining was made to examine the expression of adhesion molecules including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1) on the vascular endothelium and to determine the presence of P-selection. Moreover, the intensity of the expression of ICAM-1 on the bronchial epithelium was investigated. The number of eosinophils, mast cells, T lymphocytes and macrophages were significantly decreased, and the expression of ICAM-1, VCAM-1 and ELAM-1 were significantly inhibited by the administration of DSCG. There were significant correlations between ICAM-1 and the number of T lymphocytes, and between VCAM-1 and the number of eosinophils. These results suggest that DSCG inhibits the expression of adhesion molecules as an anti-inflammatory action, and decreases the number of inflammatory cells in the airways of asthmatic patients.

  18. Prevention of exercise-induced asthma by a fixed combination of disodium cromoglycate plus reproterol compared with montelukast in young patients.

    PubMed

    Lecheler, Josef; Pfannebecker, Bernhard; Nguyen, Duc Tung; Petzold, Ursula; Munzel, Ullrich; Kremer, Hans-Joachim; Maus, Joachim

    2008-01-01

    The leukotriene inhibitor montelukast has been recommended against exercise-induced asthma (EIA), however, single-dose agents might be favourable in several aspects. To compare the protective effects against EIA of a single inhalation of the combination disodium cromoglycate (DSCG, CAS 16110-51-3) and reproterol (REP, CAS 54063-54-6) with 3 days oral treatment of montelukast (MON, CAS 158966-92-8). Open-label, cross-over, single-centre trial. Twenty-four 6 to 18-year-old children and adolescents, with reversible and stable airway obstruction, baseline FEV1 > or = 70%, predicted and proven EIA (i.e. a maximum decrease of FEV1 by > or = 20% compared with baseline) were treated with MON, orally for 3 days in the evening, or one single inhalation of DSCG/REP 20 min before the exercise challenge. The treatment sequence was randomised. The exercise test on a treadmill was performed under standardised conditions. 24 patients completed both periods. Both treatments clearly provided protection against EIA; however, protection of DSCG/REP was more pronounced than that of MON. This difference was statistically significant even if the data were adjusted for the increase in FEV1 between inhalation of DSCG/REP and challenge (DSCG/REP(adjusted). The nadir FEV1 level after exercise following prophylaxis with DSCG/REP was even higher than the pre-inhalation FEV1 value. From these data, protection indices of 66%, 81%, and 113% for MON, DSCG/REP(adjusted), and DSCG/REP(unadjusted), respectively, were estimated. Inhalation of DSCG/REP before exercise provides significantly better protection against EIA than three days treatment with MON.

  19. [Protection from exertion-induced bronchial asthma with disodium cromoglycate (DSCG) (cromolyn, lomudal, intal) and with ketotifen (zaditen). Doubly crossed double-blind study ].

    PubMed

    Gmür, H; Scherrer, M

    1979-06-09

    16 cooperative asthmatic patients with exercise-induced asthma (with more than 15% decrease in FEV1 after strenuous work on a treadmill with 10% upward; pulse rates over 180 per minute during the work-phase) were selected to take part in a double-blind crossover trial. The 8 women and 8 men, with ages ranging from 15 to 57 years (mean 25) underwent 4 exercise tests. The effects on exercise-induced asthma of 20 mg disodium cromoglycate (DSCG) inhaled with a spinhaler 30 minutes before exercise were compared to 2 mg of ketotifen taken orally 3 hours before exercise, and likewise DSCG was compared to a placebo powder inhaled with a spinhaler, and ketotifen with placebo tablets. The whole study lasted from January to March. Ten minutes after exercise the following changes in FEV1 (in percent of control value measured before exercise) were seen: after inhalation of a placebo powder the FEV1 decreased to 66% with an almost equal decrease after taking placebo tablets (67%) (0.45 greater than p greater than 0.40) whereas, in comparison, the decrease in FEV1 after DSCG (84%) is smaller than that after inhalation of a placebo powder (66%) (p less than 0.0025). In contrast to these results was the equal decrease in FEV1 after ketotifen (70%) (0.35 greater than p greater than 0.30) and placebo tablets (67%). Although a relatively high chosen dosage of ketotifen was given, it does not seem capable of inhibiting mediator release from the bronchial mast-cells as DSCG does. It is concluded that ketotifen given orally 3 hours before the exercise test is not effective against exercise-induced asthma.

  20. The effect of disodium cromoglycate (DSCG) on in vitro proliferation of CD4+, CD8+, and CD19+ cell populations derived from allergic and healthy donors.

    PubMed

    Holen, E; Elsayed, S

    1995-03-01

    The effect of disodium cromoglycate (DSCG) on in vitro proliferation of CD4+ and CD8+ T cells and CD19+ B cells, positively selected by immunomagnetic separation, was investigated. The cells were obtained from allergic patients with moderate serum IgE levels and mild to moderate atopic dermatitis, and healthy controls. The different cell subfractions were stimulated with mitogens or specific allergens, as well as cell supernatants from the lymphoblastoid B- (RPMI 8866) and T-hybridoma (166 A2) cell lines. Proliferative responses of T- and B-cell subsets stimulated with mitogens together with recombinant interleukin-2 (rIL-2) or accessory cells (AC) could be inhibited by DSCG. In allergic individuals, significant allergen-specific stimulation could be observed in the CD8-depleted peripheral blood mononuclear cell (PBMC) fractions. Isolated CD4+ T cells, without AC or IL-2, could also be stimulated with specific allergen, but the responses were rather low. DSCG inhibited, concentration dependently, all allergen-induced responses. Interestingly, only atopic derived CD4+ and CD8+ T cells were stimulated by soluble low-affinity IgE receptor (Fc epsilon RII/sCD23) and IgE binding factor (IgEBF), including IgE enhancing factor, present in culture supernatants from RPMI 8866 and 166 A2, respectively. These responses were also inhibited by DSCG. This was in contrast to the amplifying effect of DSCG on spontaneously proliferating RPMI 8866 and 166 A2 cells, cultured in fresh cRPMI 1640 medium without sCD23 and IgE enhancing factor. Our results show that DSCG delivers an inhibitory signal or signals to PBMC subpopulations expressing Fc epsilon RII/sCD23, either upregulated by phytohemagglutinin in normal and atopic cells, or by allergens or sCD23 in atopic cells.(ABSTRACT TRUNCATED AT 250 WORDS)

  1. The effect of vehicle on physical properties and aerosolisation behaviour of disodium cromoglycate microparticles spray dried alone or with L-leucine.

    PubMed

    Najafabadi, Abdolhossien Rouholamini; Gilani, Kambiz; Barghi, Mohammadali; Rafiee-Tehrani, Morteza

    2004-11-05

    The aim of this study was to improve the aerosolisation behaviour of disodium cromogycate (DSCG), using spray drying technique. The effect of vehicle on the drug particle properties was investigated. L-leucine was selected as a natural antiadherent amino acid to improve the deagglomeration of DSCG particles. Spray dried samples of DSCG alone or with L-leucine were prepared from water and ethanol under the same conditions. The powder properties of the samples were examined by laser diffraction, helium densitometer, X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. The in vitro deposition was determined, using an Andersen cascade impactor with a Spinhaler at a flow rate of 60 l/min. An amorphous form of the drug was obtained when water was used. However, crystal transformation of original DSCG in the presence of ethanol during spray drying resulted in production of elongated particles. These particles exhibited improved aerodynamic properties, compared to the amorphous and commercial materials. Significant differences in fine particle fraction were observed using the two vehicles. Co-spray drying of DSCG and L-leucine improved the deposition profiles of the drug. These results indicated that the change in crystal structure of DSCG during spray drying process was susceptible to the nature of the vehicle. A crystalline form of DSCG with good aerodynamic properties was achieved during spray drying process. In addition, the processing of DSCG with L-leucine in a single step using ethanol resulted in an improvement in dispersion properties of the drug particles. copyright 2004 Elsevier B.V.

  2. Kinetics of the alkaline phosphatase catalyzed hydrolysis of disodium p-nitrophenyl phosphate: effects of carbohydrate additives, low temperature, and freezing.

    PubMed

    Terefe, Netsanet Shiferaw; Arimi, Joshua Mbaabu; Van Loey, Ann; Hendrickx, Marc

    2004-01-01

    The kinetics of the alkaline phosphatase catalyzed hydrolysis of disodium p-nitrphenyl phosphate was studied at 25 degrees C in the presence of the carbohydrates sucrose, fructose, lactose, maltodextrin (DE = 13-17), carboxymethylcellulose (CMC), and CMC-lactose (in 1:1 proportion) at different concentrations and in the presence of sucrose at two different concentrations in a temperature range between 25 and -10 degrees C in subcooled and frozen systems. The objective was to determine whether the reaction is diffusion-controlled, to gain an insight about the factors that determine the diffusion of the reaction species, to understand the mechanism through which the different carbohydrate additives affect the kinetics of the reaction, and to determine the effect of low temperature and freezing on the structural conformation of the enzyme. It was found that the alkaline phosphatase catalyzed hydrolysis of DNPP under the condition studied is at least partially diffusion-controlled. The results also indicate that the diffusion is not controlled by the macroviscosity of the reaction media. The concentration and type of the molecules that constitute the background matrix seem to be the main factors governing the reaction. The results indicate that the different carbohydrates affect the kinetics of the reaction through the excluded volume effect of molecular crowding and decreased substrate and product diffusion rate and not through nonspecific solute effects, which may cause protein denaturation and alteration in enzyme activity. Low temperature does not seem to affect the structural conformation of the enzyme in the temperature range studied, whereas freezing affected the catalytic properties of the enzyme perhaps through its effect on the structural conformation of the enzyme.

  3. 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.

  4. Disodium pentaborate decahydrate (DPD) induced apoptosis by decreasing hTERT enzyme activity and disrupting F-actin organization of prostate cancer cells.

    PubMed

    Korkmaz, Mehmet; Avcı, Cigir Biray; Gunduz, Cumhur; Aygunes, Duygu; Erbaykent-Tepedelen, Burcu

    2014-02-01

    Animal and cell culture studies have showed that boron and its derivatives may be promising anticancer agents in prostate cancer treatment. Thus, DU145 cells were treated with disodium pentaborate decahydrate (DPD) for 24, 48, and 72 h in order to investigate the inhibitor effect and mechanisms of DPD. Then, cell proliferation, telomerase enzyme activity, actin polymerization, and apoptosis were detected by WST-1 assay, qRT-PCR, immunofluorescence labeling, and flow cytometry, respectively. We found that DPD inhibited the growth of human prostate cancer cell line DU145 at the concentration of 3.5 mM for 24 h. Our results demonstrated that 7 mM of DPD treatment prevented the telomerase enzyme activity at the rate of 38 %. Furthermore, DPD has an apoptotic effect on DU145 cells which were examined by labeling DNA breaks. With 7 mM of DPD treatment, 8, 14, and 41 % of apoptotic cells were detected for 24, 48, and 72 h, respectively. Additionally, immunofluorescence labeling showed that the normal organization of actin filaments was disrupted in DPD-exposed cells, which is accompanied by the alteration of cell shape and by apoptosis in targeted cells. Taken together, the results indicate that DPD may exert its cytotoxicity at least partly by interfering with the dynamic properties of actin polymerization and decreasing the telomerase activity. Eventually, for the first time, the results of this study showed that DPD suppressed the activity of telomerase in DU145 cells, and therefore, we suggested that DPD could be an important agent for its therapeutic potential in the treatment of prostate cancer.

  5. Manipulations of zinc in the spinal cord, by intrathecal injection of zinc chloride, disodium-calcium-EDTA, or dipicolinic acid, alter nociceptive activity in mice.

    PubMed

    Larson, A A; Kitto, K F

    1997-09-01

    Zinc is concentrated in the dorsal horn of the spinal cord and has been proposed to alter excitability of primary afferent C-fibers, structures believed to be important in nociceptive transmission. Based on the inhibitory effect of zinc on the activity of various other neurotransmitters that play a role in nociception, we tested the hypothesis that zinc modulates pain transmission. To test this, we examined the effect of exogenous zinc, administered intrathecally (i.t.), on nociception in the mouse. We also assessed the impact of decreased concentrations of endogenously occurring zinc in the extracellular fluid brought about by an i.t. injection of either ethylenediaminetetraacetic acid disodium-calcium salt (Ca++EDTA), a calcium-saturated, membrane-impermeable chelator of divalent cations, or of dipicolinic acid, a zinc chelator. Injection of zinc produced a dose-related antinociceptive effect, optimal at 90 min in the writhing assay, but had no effect on tail-flick response latencies. In contrast, injection of either Ca++EDTA or dipicolinic acid produced a dose-related hyperalgesia in the tail-flick assay at 90 min after injection. Responses induced in the writhing assay were unaffected by Ca++EDTA. Although zinc had no effect on thermal nociception, the hyperalgesic effect of Ca++EDTA was antagonized by coadministration of Ca++EDTA with zinc. Similarly, the antinociceptive effect of zinc on writhing responses was attenuated when coadministered with Ca++EDTA. Zinc also inhibited primary afferent C-fiber activity because 10 ng of zinc i.t. inhibited the behavioral response induced by injection i.t. of 1 nmol of capsaicin. Neither zinc nor Ca++EDTA altered writhing or tail-flick latencies, respectively, when injected intracerebroventricularly. These findings support the hypothesis that endogenous zinc, localized in the dorsal horn of the spinal cord, plays a role in the regulation of pain.

  6. Dialyzability of minerals in corn masa gruel (atole) fortified with different iron compounds: effects of ascorbic acid, disodium EDTA, and phytic acid.

    PubMed

    De-Regil, Luz Maria; Casanueva, Esther; Killilea, David W; Viteri, Fernando E

    2007-06-01

    Lime-treated corn gruel (atole) is a common weaning food in iron-deficient populations, especially in Mexico and Central America, and is a potential vehicle for fortification with iron. The objective of this study was to screen promising iron compounds for use in the fortification of atole, using in vitro enzymatic digestion-dialysis techniques, while also considering their response to known iron absorption enhancers and inhibitors. Atole, unaltered or preincubated with phytase, was fortified with iron (10 mg/L) from ferrous sulfate, ferrous bisglycinate, or ferrous fumarate, or with ferric chloride, ferric ammonium citrate, or ferric sodium ethylenediaminetetraacetic acid (NaFeEDTA), and submitted to in vitro digestion. Dialysis of calcium, copper, iron, phosphorus, and zinc (analyzed by inductively coupled plasma atomic emission spectrometry) was measured when atole was fortified with iron compounds alone or together with ascorbic acid or disodium ethylenediaminetetraacetic acid (Na2EDTA). Iron dialyzability was higher with NaFeEDTA (p < .05) than with all other iron compounds, which did not differ among themselves in iron dialyzability. Addition of ascorbic acid had no significant effect on iron dialysis, whereas Na2EDTA enhanced iron dialyzability by 7 to 10 times in unaltered atole and 15 to 20 times in phytase-preincubated atole (p < .05). Addition of Na2EDTA always increased intrinsic zinc dialyzability, and most of the time this increase was significant. Phytase pretreatment generally increased mineral dialysis. Adding EDTA (either as NaFeEDTA or as Na2EDTA) to atole can increase the dialyzability of ferrous and ferric iron compounds and enhance the dialyzability of intrinsic zinc without any negative effects on calcium, phosphorus, or copper dialysis.

  7. The course of selected bone resorption marker concentrations in response to short-term hypocalcemia experimentally induced with disodium EDTA infusions in dairy cows.

    PubMed

    Liesegang, A; Eicher, R; Sassi, M L; Risteli, J; Riond, J L; Wanner, M

    2000-10-01

    The collagen metabolites hydroxyproline (HYP), deoxypyridinoline (DPD), and the carboxyterminal telopeptide of type I collagen (ICTP) are suitable markers for bone resorption in humans and several animal species. The purpose of this study was to describe the course of bone resorption markers during short-term hypocalcemia induced with disodium ethylenediaminetetraacetic acid (Na2EDTA) and to investigate whether bone resorption is increased in dairy cows under these conditions. EDTA infusions have been used as a model for periparturient paresis in dairy cows and to estimate the calcium mobilization rate from body reserves in ruminants. In this study, hypocalcemia was induced by means of a 5% Na2EDTA infusion (0.55 mg/kg/min Na2EDTA for 5 h = total dose of 100.6 g). Two experiments were conducted: (1) Six 4-11 years-old Brown Swiss cows were infused intravenously with EDTA for 5 h. Blood and urine samples were taken repeatedly from 1 day before until 10 days after infusion. (2) Towards the end of the lactation, the experiment was repeated with the same animals after a 14-day-period of feeding a low calcium diet (26 g/animal per day). The EDTA-infusion induced hypocalcemia and hypophosphatemia. The HYP-, DPD- and ICTP-concentration remained mainly unaffected during both infusions. Only DPD showed an increase during infusion and HYP an increase 2 days after the infusion. In conclusion, the EDTA infusion had little effect on the concentrations of the measured bone markers, which may be due to the fact that the serum calcium pool was refilled by increased absorption of Ca via the gastrointestinal tract. From these results, it can be concluded that bone resorption was not influenced by EDTA infusion.

  8. Influence of disodium (1-hydroxythylidene) diphosphonate on bonding between glass-ceramics containing apatite and wollastonite and mature male rabbit bone.

    PubMed

    Kitsugi, T; Yamamuro, T; Nakamura, T; Oka, M; Kokubo, T

    1993-05-01

    It has been reported that bioactive glass-ceramics containing crystalline oxy- and fluoroapatite [Ca10(PO4)6(O,F2) and wollastonite (CaSiO3), chemical composition: MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, CaF2 0.5 in weight ratio] bond to bone tissue through the formation of an apatite (a calcium and phosphorus-rich layer) on the ceramic surface. In this study, the influence of disodium (1-hydroxythylidene) diphosphonate (DHTD) on the bonding between bone and glass-ceramics containing apatite and wollastonite was investigated. Rectangular ceramic plates (15 mm x 10 mm x 2 mm, abraded with #2000 alumina powder) were implanted into the tibial bone of mature male rabbits. DHTD was administered daily by subcutaneous injection to groups 1-5: group 1-4 at doses of 20, 5.0, 1.0, and 0.1 mg/kg body wt/day for 8 weeks; and group 5 at a dose of 5 mg/kg body wt/day for 4 weeks. Group 6 was given injections of saline as a control. At 8 weeks after implantation, the rabbits were killed. The tibiae containing the ceramics were dissected out and used for a detachment test. The failure load, when an implant became detached from the bone, or when the bone itself broke, was measured. The failure loads for groups 1-6 were 0 kg, 0 kg, 8.08 +/- 2.43 kg, 7.28 +/- 2.07 kg, 5.56 +/- 1.63 kg, and 6.38 +/- 1.30 kg, respectively. Ceramic bonding to bone tissue was inhibited by a higher dose of DHTD (groups 1 and 2).(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Management of Pneumonia and Blood Stream Infections with New Antibiotic Adjuvant Entity (Ceftriaxone + Sulbactam + Disodium Edetate)- A Novel Way to Spare Carbapenems

    PubMed Central

    Mir, Mohammad Amin

    2016-01-01

    Introduction Nosocomial infections have been considered as a major health problem causing incremental morbidity, mortality and costs of therapy. Aim This retrospective study was initiated with aim to analyse the comparative efficacy of a novel Antibiotic Adjuvant Entity (AAE), a combination of ceftriaxone + sulbactam + disodium edetate and meropenem in combination with colistin, for the management of Multi Drug Resistant (MDR) nosocomial Gram-negative bacterial infections. Materials and Methods Case history sheets of patients with documented MDR nosocomial Gram-negative infections who received either AAE or meropenem in combination with colistin for management of infections over a period of 3 years (November 2012 – October 2015) were included in the study. Data related to clinical management, demographics, vital signs and laboratory parameters along with prior antibiotic therapy, dose and clinical outcomes were evaluated thoroughly to analyse the clinical benefits of this new AAE+ colistin therapy for management of MDR nosocomial infections. Results Out of 115 patients short listed for the study, 52 patients had received AAE + colistin therapy and 63 patients have received meropenem + colistin. AAE + colistin therapy resulted in significantly higher efficacy (86.53%) as compared to meropenem + colistin (63.49%). A rising trend in clinical cure rates was observed in AAE based combination therapy in contrast to the decreasing trend in meropenem based combination therapy. A progressive decline in clinical cure rates was observed in meropenem treated group over a period of 3 years due to rising carbapenemases and multiple resistance by pathogens, where as AAE maintained the same efficacy. Conclusion The AAE + colistin therapy has shown better bacteriological and clinical efficacy as compared to meropenem + colistin in the management of various nosocomial MDR Gram-negative infections. A significant number of meropenem failure patients responded to the AAE therapy

  10. Probing the Interaction between a DNA Nucleotide (Adenosine-5'-Monophosphate Disodium) and Surface Active Ionic Liquids by Rotational Relaxation Measurement and Fluorescence Correlation Spectroscopy.

    PubMed

    Roy, Arpita; Banerjee, Pavel; Dutta, Rupam; Kundu, Sangita; Sarkar, Nilmoni

    2016-10-02

    This article demonstrates the interaction of a deoxyribonucleic acid (DNA) nucleotide, adenosine-5'-monophosphate disodium (AMP) with a cationic surface active ionic liquid (SAIL) 1-dodecyl-3-methylimidazoium chloride (C12mimCl) and an anionic SAIL, 1-butyl-3-methylimidazolium n-octylsulfate ([C4mim][C8SO4]). Dynamic light scattering (DLS) measurements and 1H NMR (nuclear magnetic resonance) studies indicate that substantial interaction is taking place among the DNA nucleotide, AMP and the SAILs. Moreover, cryogenic transmission electron microscopy (cryo-TEM) suggests that SAILs containing micellar assemblies are transformed into larger micellar assemblies in presence of DNA nucleotide. Additionally, the rotational motion of two oppositely charged molecules, Rhodamine 6G perchlorate (R6G) and Fluorescein sodium salt (Fl-Na) have been monitored in these aggregates. The rotational motion of R6G and Fl-Na differs significantly between SAILs micelles, and SAILs-AMP containing larger micellar aggregates. The effect of negatively charged DNA nucleotide (AMP) addition into the cationic and anionic SAILs is more prominent for the cationic charged molecule R6G than that of anionic probe Fl-Na due to the favourable electrostatic interaction between the AMP and cationic R6G. Moreover, the influence of the anionic DNA nucleotide on the cationic and anionic SAIL micelles is monitored through the variation of the lateral diffusion motion of oppositely charged probe molecules (R6G and Fl-Na) inside these aggregates. This variation in diffusion coefficient values also suggests that interaction pattern of these oppositely charged probes are different within the SAILs-nucleotide containing aggregates. Therefore, both rotational and translational diffusion measurements confirm that the DNA nucleotide (AMP) renders more rigid microenvironment within the micellar solution of SAILs.

  11. A comparative study of the effects of ketotifen, disodium cromoglycate, and beclomethasone dipropionate on bronchial mucosa and asthma symptoms in patients with atopic asthma.

    PubMed

    Hoshino, M; Nakamura, Y; Sim, J J; Tomioka, H

    1998-07-01

    Asthma is a chronic inflammatory disorder of the airways that is characterized by infiltration of many inflammatory cells into the bronchial mucosa. We compared the effects of ketotifen, disodium cromoglycate (DSCG), and beclomethasone dipropionate (BDP) on inflammatory cells in the bronchial mucosa and on the asthma symptoms of patients with atopic asthma. In this 12-week parallel study, 32 patients were randomly allocated to either the ketotifen group (2 mg day-1, n = 13), DSCG group (8 mg day-1, n = 9) or BDP (400 micrograms day-1, n = 10). Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Before and after treatment, pulmonary function and bronchial responsiveness to methacholine were evaluated, and fibreoptic bronchoscopy and biopsy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. We performed immunohistochemistry using specific monoclonal antibodies for activated eosinophils (EG2), mast cells (AA1), and T cells (CD3, CD4, and CD8). Our clinical findings showed significant improvement in symptom score and bronchial responsiveness (P < 0.01) each) in all groups. Both the DSCG and the BDP groups had significantly better symptom scores than the ketotifen group (P < 0.05, both groups). PEF significantly increased in the DSCG group in comparison to the ketotifen (P < 0.01) and BDP (P < 0.05) groups, FEV1% increased significantly in the DSCG (P < 0.01) and BDP (P < 0.05) groups in comparison to the ketotifen group. Compared with their baseline values, treatment significantly decreased EG2+ activated eosinophils, and CD3+ and CD4+ T cells, in each group (P < 0.01). Both the DSCG (P < 0.05) and the BDP groups (P < 0.01) exhibited significant decreases in AA1+ mast cell count, but this was not observed in the ketotifen group. Comparing before- and after-treatment values, only the DSCG group exhibited a significant decrease in the number of CD8+ T cells (P < 0.01). Ketotifen, DSCG, and BDP all showed

  12. Effect of Mineral Trioxide Aggregate, Calcium-Enriched Mixture Cement and Mineral Trioxide Aggregate with Disodium Hydrogen Phosphate on BMP-2 Production.

    PubMed

    Ghasemi, Negin; Rahimi, Saeed; Lotfi, Mehrdad; Solaimanirad, Jafar; Shahi, Shahriar; Shafaie, Hajar; Salem Milani, Amin; Shakuie, Sahar; Zand, Vahid; Abdolrahimi, Majid

    2014-01-01

    One of the hypotheses regarding the calcification induction by mineral trioxide aggregate (MTA) is the involvement of transforming growth factor-Beta (TGF-β) super family. Calcium-enriched mixture (CEM) cement is one of the endodontic biomaterials with clinical applications similar to MTA. The aim of the present in vitro study was to compare the induction of bone morphogenic protein-2 (BMP-2) by a combination of disodium hydrogen phosphate (DSHP) and tooth colored ProRoot MTA (WMTA), to that of CEM cement and WMTA. Human gingival fibroblasts (HGFs) were obtained from the attached gingiva of human premolars. HGFs were cultured in Dulbecco's Modified Eagle's medium, supplemented with 10% fetal calf serum, penicillin, and streptomycin. Cells in groups 1, 2 and 3 were exposed to WMTA, CEM and WMTA+DSHP discs, respectively. The fourth group served as the control. After 72 h of exposure, HGF viability was determined by Mosmann's tetrazolium toxicity (MTT) assay. BMP-2 levels in cell-free culture media were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using the one-way ANOVA, followed by the post hoc Games-Howell test for BMP-2 and post hoc Tukey's test for the results of MTT assay. Cellular viability was significantly higher in group 3 compared to the other groups (P<0.05); however, CEM and WMTA did not exhibit significant differences (P=0.08). The control group exhibited significantly higher cellular viability in comparison to the other groups of the study (P<0.05). The highest and lowest protein production rates were observed in the WMTA (3167±274.46 pg/mL) and WMTA+DSHP (1796±839.49 pg/mL) groups, respectively. There were no significant differences between the control, WMTA and CEM groups (P>0.05). WMTA and CEM did not exhibit any significant differences in terms of inducing BMP-2 production; however, incorporation of DSHP into WMTA resulted in a decrease in the induction of this protein.

  13. [HUMAN ADIPOSE-DERIVED STEM CELLS COMBINED WITH SMALL INTESNITAL SUBMUCOSA POWDER/CHITOSAN CHLORIDE-β-GLYCEROL PHOSPHATE DISODIUM-HYDROXYETHYL CELLULOSE HYBRID FOR ADIPOSE TISSUE ENGINEERING].

    PubMed

    Zhang, Shu; Luo, Jingcong; Lü, Qing; Deng, Xueqin; Xiong, Bingjun

    2015-08-01

    To study the feasibility of human adipose-derived stem cells (hADSCs) combined with small intestinal submucosa powder (SISP)/chitosan chloride (CSCl)-β-glycerol phosphate disodium (GP)-hydroxyethyl cellulose (HEC) for adipose tissue engineering. hADSCs were isolated from human breast fat with collagenase type I digestion, and the third passage hADSCs were mixed with SISP/CSCl-GP-HEC at a density of 1 x 10(6) cells/mL. Twenty-four healthy female nude mice of 5 weeks old were randomly divided into experimental group (n = 12) and control group (n=12), and the mice were subcutaneously injected with 1 mL hADSCs+SISP/CSCl-GP-HEC or SISP/CSCl-GP-HEC respectively at the neck. The degradation rate was evaluated by implant volume measurement at 0, 1, 2, 4, and 8 weeks. Three mice were euthanized at 1, 2, 4, and 8 weeks respectively for general, histological, and immunohistochemical observations. The ability of adipogenesis (Oil O staining), angiopoiesis (CD31), and localized the hADSCs (immunostaining for human Vimentin) were identified. The volume of implants of both groups decreased with time, but it was greater in experimental group than the control group, showing significant difference at 8 weeks (t = 3.348, P = 0.029). The general observation showed that the border of implants was clear with no adhesion at each time point; fat-liked new tissues were observed with capillaries on the surface at 8 weeks in 2 groups. The histological examinations showed that the structure of implants got compact gradually after injection, and SISP gradually degraded with slower degradation speed in experimental group; adipose tissue began to form, and some mature adipose tissue was observed at 8 weeks in the experimental group. The Oil O staining positive area of experimental group was greater than that of the control group at each time point, showing significant difference at 8 weeks (t = 3.41 1, P = 0.027). Immunohistochemical staining for Vemintin showed that hADSCs could survive at

  14. 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

  15. Lead-induced oxidative stress and hematological alterations and their response to combined administration of calcium disodium EDTA with a thiol chelator in rats.

    PubMed

    Saxena, Geetu; Flora, S J S

    2004-01-01

    The therapeutic efficacy of calcium disodium ethylenediaminetetracetic acid (CaNa(2)EDTA) and the two thiol chelators, 2,3-dimercaptopropane 1-sulfonate (DMPS) and monoisoamyl dimercaptosuccinic acid (MiADMSA) was studied, both individually and in combination, in reducing lead concentration in blood and soft tissues and in restoring lead induced altered biochemical variables in rats. Exposure to subacute dose of lead implicated a critical role of reactive oxygen species (ROS) and oxidative stress in altering the normal values of these variables. Exposure to lead caused a significant inhibition of blood delta-aminolevulinic acid dehydratase (ALAD), an important enzyme in the haem synthesis pathway and glutathione (GSH) level. These changes were also accompanied by inhibition of ALAD activity in kidney, delta-aminolevulinic acid synthase (ALAS) activities in liver and changes in platelet counts in whole blood suggesting disturbed haem synthesis pathway. Lead exposure also led to a pronounced depletion of brain GSH contents, superoxide dismutase (SOD) activity, an increase in thiobarbituric acid reactive substances (TBARS), and activity of glutathione S-transferase (GST). Specific activities of membrane-bound enzymes, acetylcholinesterase (AChE) and monoamine oxidase (MAO), were significantly inhibited on lead exposure. These biochemical changes were correlated with increased uptake of lead in blood and soft tissues. Post lead exposure treatment with MiADMSA in particular provided significant recovery in altered biochemical variables besides significant depletion of tissue lead burden. Treatment with CaNa(2)EDTA and DMPS individually had only moderate beneficial effects on tissue oxidative stress, although they were equally effective in the removal of tissue lead burden. Tissue zinc and copper levels did not depict any significant depletion, although changes like marked depletion of zinc following CaNa(2)EDTA and copper after MiADMSA administration were of some

  16. Effect of Mineral Trioxide Aggregate, Calcium-Enriched Mixture Cement and Mineral Trioxide Aggregate with Disodium Hydrogen Phosphate on BMP-2 Production

    PubMed Central

    Ghasemi, Negin; Rahimi, Saeed; Lotfi, Mehrdad; Solaimanirad, Jafar; Shahi, Shahriar; Shafaie, Hajar; Salem Milani, Amin; Shakuie, Sahar; Zand, Vahid; Abdolrahimi, Majid

    2014-01-01

    Introduction: One of the hypotheses regarding the calcification induction by mineral trioxide aggregate (MTA) is the involvement of transforming growth factor-Beta (TGF-β) super family. Calcium-enriched mixture (CEM) cement is one of the endodontic biomaterials with clinical applications similar to MTA. The aim of the present in vitro study was to compare the induction of bone morphogenic protein-2 (BMP-2) by a combination of disodium hydrogen phosphate (DSHP) and tooth colored ProRoot MTA (WMTA), to that of CEM cement and WMTA. Methods and Materials: Human gingival fibroblasts (HGFs) were obtained from the attached gingiva of human premolars. HGFs were cultured in Dulbecco’s Modified Eagle’s medium, supplemented with 10% fetal calf serum, penicillin, and streptomycin. Cells in groups 1, 2 and 3 were exposed to WMTA, CEM and WMTA+DSHP discs, respectively. The fourth group served as the control. After 72 h of exposure, HGF viability was determined by Mosmann’s tetrazolium toxicity (MTT) assay. BMP-2 levels in cell-free culture media were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using the one-way ANOVA, followed by the post hoc Games-Howell test for BMP-2 and post hoc Tukey’s test for the results of MTT assay. Results: Cellular viability was significantly higher in group 3 compared to the other groups (P<0.05); however, CEM and WMTA did not exhibit significant differences (P=0.08). The control group exhibited significantly higher cellular viability in comparison to the other groups of the study (P<0.05). The highest and lowest protein production rates were observed in the WMTA (3167±274.46 pg/mL) and WMTA+DSHP (1796±839.49 pg/mL) groups, respectively. There were no significant differences between the control, WMTA and CEM groups (P>0.05). Conclusion: WMTA and CEM did not exhibit any significant differences in terms of inducing BMP-2 production; however, incorporation of DSHP into WMTA resulted in a

  17. Tolerability and in vivo performance of a novel freon-free metered dose inhaler for a fixed combinational product of reproterol and disodium cromoglycate.

    PubMed

    Hermann, R; Ruus, P; Schneider, E; de Mey, C

    1998-06-01

    The present study was conducted to describe and compare the in vivo performance (systemic exposure), clinical and laboratory safety of a fixed combinational product of inhaled reproterol (CAS 54063-54-6) plus disodium cromoglycate (DSCG; CAS 15826-37-6) using a novel freon (CFC)-free metered dose inhaler (MDI), which uses 1,1,1,2,3,3,3-heptafluoropropane (HFA-227; CAS 431-89-0) as propellant and polyoxyethylene glyceryl trioleate (Tagat TO; CAS 68958-64-5) as surfactant relative to the conventional freon-driven MDI Allergospasmin in healthy male and female volunteers. Twenty-four young male and female healthy subjects were randomly allocated in gender-balanced fashion to 4 parallel treatment groups with single and repeated dosing of either reproterol + DSCG by HFA- or CFC-MDI (each time N = 8) or placebo by HFA- or CFC-MDI (each time N = 4) using matched placebo devices thus allowing a double-blind (with regard to placebo) approach. Treatments consisted of a single morning dose of 2 actuations followed 4 days later by a 1 week treatment course of 2 actuations four times daily. Subjects were investigated extensively in terms of blood pressure, pulse rate, electrocardiography, spirometry, respiratory rate, body temperature, laboratory safety (haematology, clinical chemistry, urinalysis) and clinical well-being. There were no treatment, compound or device related effects for any of the tolerability and safety end points. The treatments were well tolerated. In particular, there was no irritative cough or any sign of broncho-irritation on application. Adverse events were reported in a total of 9 subjects: 3/8, 4/8, 0/4 and 2/4 subjects treated with reproterol + DSCG by HFA-MDI, reproterol + DSCG by CFC-MDI, placebo by HFA-MDI and placebo by CFC-MDI, respectively. Of these, 6 events in 6 subjects receiving the active treatments were considered probably or definitely related to the test drug administration (i.e. adverse drug reactions): after reproterol + DSCG one subject

  18. Effect of antihistamines, disodium cromoglycate (DSCG) or methysergide on post-irradiation cerebral blood flow and mean systemic arterial blood pressure in primates after 25 Gy, whole-body, gamma irradiation.

    PubMed

    Cockerham, L G; Forcino, C D

    1995-06-01

    Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA) and serotonin (5-HT). To investigate the relationship among these responses, rhesus monkeys (Macaca mulatta) received physiological saline (i.v.), disodium cromoglycate (DSCG), antihistamines (AH, mepyramine and cimetidine), or methysergide (METH), then were given 25 Gy whole-body irradiation. Monkeys receiving DSCG, AH or METH had higher post-irradiation mean arterial blood pressure (MBP) than saline-treated controls. Compared to levels in controls, post-irradiation hippocampal blood flow (rCBF) levels were higher in monkeys receiving DSCG, AH or METH. Treatment with the 5-HT2 receptor antagonist methysergide was the most effective in maintaining both rCBF and MBP after irradiation. Results support the hypothesis that the irradiation-induced cerebral ischemia and, to some extent, the hypotension is mediated by serotonin through 5-HT2 receptor sites.

  19. A redetermination of the structure of poly[[μ(4)-(R)-2-ammonio-3-sulfonato-propano-ato]aqua-sodium], originally reported as poly[[μ(7)-l-cysteato(2-)]disodium].

    PubMed

    Brown, I David

    2012-04-01

    The structure originally reported as poly[[μ(7)-l-cysteato(2-)]disodium], [Na(2)(C(3)H(5)NO(5)S)](n) [Liu (2002). Acta Cryst. E67, m1346-m1347], has been redetermined with one of the sodium atoms replaced with a water mol-ecule and an additional proton attached to the amine group, resulting in the revised formula [Na{CO(2)CH(CH(2)SO(3))NH(3)}(H(2)O)](n). The agreement index, wR, has been reduced from 0.159 to 0.087 and the global instability index from 0.56 vu (valence units) to the acceptable value of 0.11 vu.

  20. 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.

  1. The effect of disodium cromoglycate (DSCG) on the levels of albumin and the immunoglobulins IgA, IgG, IgM and IgE in sputum.

    PubMed

    Turner, K J; Rebuck, A S

    1975-03-01

    Sputum samples from control subjects with cardiac disease and from patients with asthma were assayed for albumin content and immunoglobulins IgA, IgG, IgM and IgE. The asthmatics were divided into three groups: one group had received disodium cromoglycate (DSCG) for at least 48 hr prior to sampling, another group was sampled daily after commencing DSCG therapy and the third group were not taking DSCG. Albumin and immunoglobulins accounted for approximately 8% of the total sputum proteins in each of the four groups of subjects. There was no significant difference in the mean sputum levels of albumin or the immunoglobulins, when expressed as a percentage of total sputum proteins, between the subjects in each group. However, the ratios of IgA/albumin and IgA/IgG in the asthmatic group receiving DSCG were significantly lower than the corresponding ratios in sputa from both asthmatics and control subjects with cardiac disease. The sputum IgE levels tended to be higher in the asthmatics than in the control group, but DSCG therapy had little effect upon sputum IgE levels.

  2. The effect of disodium cromoglycate, budesonide, and cyclosporin A on interleukin-4, interleukin-5, and interleukin-13 secretions in Der p I-stimulated T cells from house dust mite-sensitive atopic and nonatopic individuals.

    PubMed

    Oh, Jae-Won; Lee, Ha-Baik; Chung, Yong-Hoon; Choi, Yong

    2002-01-01

    Disodium cromoglycate (DSCG), budesonide, and cyclosporin A (CsA) were the well-known immunomodulators for the allergic and immunologic diseases clinically. In this study, we evaluated the characteristics of inhibition on cytokine synthesis of Der p I-stimulated T cells by the same inhibiting concentrations of DSCG, budesonide, and CsA in house-dust mite antigen (Der p I)-specific atopic and nonatopic healthy individuals. Seven house dust mite allergen specific patients were recruited for this study. Seven healthy volunteers were included on the basis of negative allergic manifestations and low serum immunoglobulin E values. Peripheral blood mononuclear cells (PBMCs) were cultured in the presence of recombinant interleukin (rIL)-2 with or without budesonide, DSCG, CsA, and Der p I for 48 hours. Cells were stained with anti-CD4 fluorescein isothiocyanate-conjugated monoclonal antibody, and then anti-human IL-4 phycoerythrin, IL-5, or IL-13 monoclonal antibody, respectively, was added to both blocked and stained samples. Incubation of PBMC from atopics with each immunomodulator and Der p I resulted in the reduction of IL-4 secretion compared with Der p I alone stimulation. However, IL-4 secretion in PBMC from nonatopics was not reduced with DSCG and Der p I stimulation. IL-4, IL-5, and IL-13 secretions of PBMC from atopics were significantly decreased after incubation with each immunomodulator and Der p I, compared with after incubation with Der p I alone. These results might be considered to show either that DSCG has a selective inhibiting effect on cytokine production in T cells from atopics or is a weak inhibitor of cytokine secretions compared with budesonide and CsA at even strength for the inhibition of lymphocyte proliferation in normal, healthy individuals.

  3. Safety and efficacy of a novel drug elores (ceftriaxone+sulbactam+disodium edetate) in the management of multi-drug resistant bacterial infections in tertiary care centers: a post-marketing surveillance study.

    PubMed

    Chaudhary, Manu; Mir, Mohd Amin; Ayub, Shiekh Gazalla

    In India, Elores (CSE-1034: ceftriaxone+sulbactam+disodium edetate) was approved as a broad spectrum antibiotic in year 2011 and is used for management of Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections and identify the incidence of adverse events in real clinical settings. This Post Marketing Surveillance study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with Elores (CSE1034). Information regarding demographic, clinical and microbiological parameters, dosage and treatment duration, efficacy and adverse events (AEs) associated with the treatment were recorded. A total of 2500 patients were included in the study and efficacy was evaluated in 2487 patients. In total, 409 AEs were reported in 211 (8.4%) patients. The major AEs reported were vomiting (3.0%), pain at injection site (2.5%), nausea (2.3%), redness at site (1.96%), thrombophlebitis (1.4%). Of total reported AEs, 40 (5.3%) AEs were reported in pediatric, 310 (20.6%) in adult, and 59 (23.6%) in geriatric group. No AE belonging to grade IV or V was reported in any patient. In terms of efficacy, 1977 (79.4%) patients were cured, 501 (20.1%) patients showed clinical improvement and 5 (0.2%) patients were complete failure. The treatment duration varied from 5 to 7 days in different patients depending on the infection type. In this post-marketing surveillance study, CSE-1034 was found to be an effective and safe option against Pip tazo and meropenem in management of patients with multi-drug resistant (MDR) bacterial infections under routine ward settings. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  4. Anti-allergic and anti-inflammatory properties of a potent histamine H1 receptor antagonist, desloratadine citrate disodium injection, and its anti-inflammatory mechanism on EA.hy926 endothelial cells.

    PubMed

    Jie, Qiong; Kodithuwakku, Nandani Darshika; Yuan, Xin; He, Guangwei; Chen, Meiling; Xu, Shuhong; Wu, Yulin

    2015-05-05

    The present study, demonstrates that, desloratadine citrate disodium injection (DLC) possesses antihistaminic, anti-allergic and anti-inflammatory properties and elucidates its molecular mechanisms of anti-inflammatory properties. In vitro antihistamine activity of DLC was determined in guinea pig isolated tissues. In vivo antihistamine effects were evaluated after following intravenous administration of DLC in mice with histamine- induced paw edema and in rats with increased capillary permeability. Anti-allergic effects were assessed through passive cutaneous anaphylactic (PCA) reactions in sensitized rodents and ovalbumin-induced allergic rhinitis in rats. Anti-inflammatory properties and molecular mechanisms of DLC were determined on histamine- and lipopolysaccharide (LPS)-induced EA.hy926 endothelial cells. DLC exhibited significant and reversible inhibition of histamine-induced contractions of isolated guinea pig ileum with pA2 value of 8.88. Histamine-induced paw edema and increased capillary permeability were notably inhibited by DLC intravenous administration. In the model of PCA reactions, DLC showed significant activity in a dose-dependent nd potently inhibited both the early-phase and late-phase allergic reaction of ovalbumin-induced allergic rhinitis in rats. DLC alleviated the rhinitis symptoms and inhibited inflammatory cell infiltration, IL-4 and protein leakage in nasal lavage fluid (NLF). In EA.hy926 cells, DLC significantly inhibited the histamine- and LPS- induced IL-6 and IL-8 production and P-selectin and intercellular cell adhesion molecule-1 (ICAM-1) expression. Moreover, DLC reduced translocation of nuclear factor-kappaB (NF-κB) to the nucleus in activated EA.hy926 cells. These results provide evidence that DLC possesses potent antihistaminic, anti-allergic and, anti-inflammatory properties via suppressing IL-6, IL-8, P-selectin and ICAM-1 expression.

  5. Chelation of zinc in the extracellular area of the spinal cord, using ethylenediaminetetraacetic acid disodium-calcium salt or dipicolinic acid, inhibits the antinociceptive effect of capsaicin in adult mice.

    PubMed

    Larson, A A; Kitto, K F

    1999-02-01

    Capsaicin depolarizes primary afferent C-fibers releasing substance P (SP) whose N-terminal metabolites appear to play a role in the development of antinociception. Because some effects of SP(1-7) are similar to those of zinc, we tested the hypothesis that zinc in the extracellular area plays a role in capsaicin-induced antinociception, as measured using the abdominal stretch (writhing) assay. Decreases in zinc were achieved by intrathecal (i.t.) injection of membrane-impermeable compounds: ethylenediaminetetraacetic acid disodium-calcium salt (Ca++ EDTA), a calcium-saturated chelator of divalent cations, or dipicolinic acid, a zinc chelator. Ten nanomoles of Ca++ EDTA had no effect on writhing at either 90 min or 24 h after injection, yet pretreatment with Ca++ EDTA prevented the development of antinociception 24 h after i.t. injection of either 2. 8 nmol of capsaicin or 10 nmol of SP(1-7). One nanomole of dipicolinic acid injected i.t. also blocked capsaicin- and SP(1-7)-induced antinociception. When injected 24 h after SP(1-7), Ca++ EDTA failed to reverse antinociception. Acute antinociception produced 30 min after injection of SP(1-7) was also blocked when Ca++ EDTA was injected 24 h, but not 60 min, before SP(1-7). Thus, the optimal time of Ca++ EDTA-induced hyperalgesia (90 min), described previously, did not correspond to that of its inhibitory effect on antinociception (24 h). In contrast, we found that the previously described antinociception after an i.t. injection of zinc (90 min) is greatly attenuated by 24 h. Thus, zinc appears to be necessary, but may not be sufficient, for the long-term antinociceptive effect of capsaicin, acting downstream from the action of substance P N-terminal metabolites.

  6. A double-blind, randomized, comparative study of the use of a combination of uridine triphosphate trisodium, cytidine monophosphate disodium, and hydroxocobalamin, versus isolated treatment with hydroxocobalamin, in patients presenting with compressive neuralgias

    PubMed Central

    Goldberg, Henrique; Mibielli, Marco Antonio; Nunes, Carlos Pereira; Goldberg, Stephanie Wrobel; Buchman, Luiz; Mezitis, Spyros GE; Rzetelna, Helio; Oliveira, Lisa; Geller, Mauro; Wajnsztajn, Fernanda

    2017-01-01

    Context This paper reports on the results of treatment of compressive neuralgia using a combination of nucleotides (uridine triphosphate trisodium [UTP] and cytidine monophosphate disodium [CMP]) and vitamin B12. Objectives To assess the safety and efficacy of the combination of nucleotides (UTP and CMP) and vitamin B12 in patients presenting with neuralgia arising from neural compression associated with degenerative orthopedic alterations and trauma, and to compare these effects with isolated administration of vitamin B12. Methods A randomized, double-blind, controlled trial, consisting of a 30-day oral treatment period: Group A (n=200) receiving nucleotides + vitamin B12, and Group B (n=200) receiving vitamin B12 alone. The primary study endpoint was the percentage of subjects presenting pain visual analog scale (VAS) scores ≤20 at end of study treatment period. Secondary study endpoints included the percentage of subjects presenting improvement ≥5 points on the patient functionality questionnaire (PFQ); percentage of subjects presenting pain reduction (reduction in VAS scores at study end in relation to pretreatment); and number of subjects presenting adverse events. Results The results of this study showed a more expressive improvement in efficacy evaluations among subjects treated with the combination of nucleotides + vitamin B12, with a statistically significant superiority of the combination in pain reduction (evidenced by VAS scores). There were adverse events in both treatment groups, but these were transitory and no severe adverse event was recorded during the study period. Safety parameters were maintained throughout the study in both treatment groups. Conclusion The combination of uridine, cytidine, and vitamin B12 was safe and effective in the treatment of neuralgias arising from neural compression associated with degenerative orthopedic alterations and trauma. PMID:28243144

  7. Disodium Cromoglycate in Treatment of Asthmatic Children

    PubMed Central

    Hardy, Larry W.; Jones, R. H. Trefor

    1973-01-01

    In nearly all 38 children with asthma studied after administration of DSCG in Regina and Saskatoon, in our judgment there was marked improvement in chest symptoms, wheezing, coughing and weight gain. The patients and their families noted the same improvements. There was marked improvement in personality, school attendance, physical activity and other readily observed criteria. Other medications were sharply reduced in nearly every case. This was particularly significant in the case of steroid therapy and aerosol bronchodilators. DSCG has an important role in the treatment of properly selected cases of asthma. We noted no untoward side effects. It must be again emphasized that this drug is prophylactic and not palliative. PMID:20468871

  8. Desloratadine citrate disodium injection, a potent histamine H(1) receptor antagonist, inhibits chemokine production in ovalbumin-induced allergic rhinitis guinea pig model and histamine-induced human nasal epithelial cells via inhibiting the ERK1/2 and NF-kappa B signal cascades.

    PubMed

    Chen, Meiling; Xu, Shuhong; Zhou, Peipei; He, Guangwei; Jie, Qiong; Wu, Yulin

    2015-11-15

    Chemokines have chemotactic properties on leukocyte subsets whose modulation plays a pivotal role in allergic inflammatory processes. Our present study was designed to investigate the anti-allergic and anti-inflammatory properties of desloratadine citrate disodium injection (DLC) and elucidate the molecular mechanisms of its anti-inflammatory properties. The anti-allergic effects of DLC were evaluated based on allergic symptoms, serological marker production and histological changes of the nasal mucosa in guinea pigs model of allergic rhinitis. The anti-inflammatory properties and molecular mechanisms of DLC were explored by studying the regulation of a set of chemokines and extracellular signal-regulated kinase (ERK)1/2 and nuclear factor-kappa B (NF-κB) pathways, after DLC treatment in guinea pigs model of allergic rhinitis in vivo and histamine-activated human nasal epithelial cells (HNECs) in vitro. In vivo model in guinea pigs, DLC alleviated the rhinitis symptoms, inhibited inflammatory cells infiltration in nasal lavage fluid (NLF) and histamine, monocyte chemotactic protein (MCP)-1, regulated on activation normal T cell expressed, and presumably secreted (RANTEs) and interleukin (IL)-8 release in sera and P-ERK1/2 and NF-κB activation in nasal mucosa. In vitro, DLC markedly inhibited histamine-induced production of MCP-1, RANTEs and IL-8 and suppressed c-Raf, mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) and ERK1/2 activation in HNECs. These results provide evidence that DLC possesses potent anti-allergic and anti-inflammatory properties. The mechanism of action underlying DLC in allergic inflammation appears to be inhibition of the phosphorylation of ERK1/2, in addition to blocking of the NF-κB pathway.

  9. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...-dinitrilo) tetraacetic acid, not more than 1.0 percent. Moisture, not more than 15 percent. Water insoluble... practice: Total copper, not less than 13.5 percent. Total (ethylene-dinitrilo) tetracetic acid, not less...

  10. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... Mayonnaise 75 Do. Mushrooms (cooked canned) 200 Promote color retention. Oleomargarine 75 Preservative. Pecan pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color retention...

  11. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... Mayonnaise 75 Do. Mushrooms (cooked canned) 200 Promote color retention. Oleomargarine 75 Preservative. Pecan pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color retention...

  12. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Mayonnaise 75 Do. Mushrooms (cooked canned) 200 Promote color retention. Oleomargarine 75 Preservative. Pecan pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color retention...

  13. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., flavor, and/or product clarity. Dressings, nonstandardized 75 Preservative. Dried lima beans (cooked... Antigushing agent. French dressing 75 Preservative. Legumes (all cooked canned, other than dried lima beans, pink beans, and red beans) 365 Promote color retention. Mayonnaise 75 Do. Mushrooms (cooked canned) 200...

  14. Disodium tris­(dioxidomolybdenum) bis­(diarsenate)

    PubMed Central

    Jouini, Raja; Zid, Mohamed Faouzi; Driss, Ahmed

    2012-01-01

    The asymmetric unit of the title compound, Na2(MoO2)3(As2O7)2, is composed of two cyclic MoAs2O11 units and an MoO6 corner-sharing octa­hedron. The anionic framework can be decomposed into two types of layers, viz. MoO2As2O7 and Mo2As2O14, which use mixed Mo—O—As and As—O—Mo bridges to achieve a new three-dimensional structure with two types of large channels in which the Na+ cations are located. Two O atoms are disordered and are located in two positions close to their initial positions with occupancy ratios of 0.612 (17):0.388 (17) and 0.703 (12):0.298 (12). PMID:22589750

  15. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... beverages 25 Promote stability of color, flavor, and/or product clarity. Dressings, nonstandardized 75... consists, in a cylindrical shape, of egg white with an inner core of egg yolk 1 200 Preservative. Fermented...

  16. Mode of action and indication for disodium cromoglycate (DSCG).

    PubMed

    Kunkel, G; Baumer, F E; Okuda, M; van Cauwenberge, P

    1985-01-01

    The possible mode of action for DSCG is described. It is assumed that DSCG has a cell specific effect on mast cells, smooth muscle cells, secretory cells and nerve endings. The main action is probably due to an influence upon the calcium channel opening receptors, thus preventing consecutive mediator release from these cells. The lack of efficacy in underlying diseases (rhinitis and bronchial asthma) is probably due to other pathophysiological mechanisms involved. The possible role of bradykinin as a potent mediator is discussed. The indication of DSCG is briefly summarized.

  17. Carbenoxolone Disodium Treatment for Canine Pituitary-Dependent Hyperadrenocorticism

    PubMed Central

    Teshima, Takahiro; Matsumoto, Hirotaka; Okusa, Tomoko; Uchiyama, Rion; Koyama, Hidekazu

    2016-01-01

    Pituitary-dependent hyperadrenocorticism (PDH) is mainly caused by pituitary corticotroph tumors in dogs. A characteristic feature of corticotroph tumors is their resistance to negative feedback by glucocorticoids. In some animal species, including dogs, the aberrant expression of 11β-hydroxysteroid dehydrogenase (11HSD), a cortisol metabolic enzyme, is observed in corticotroph tumors. We previously reported that carbenoxolone (CBX), an inhibitor of 11HSD, suppressed ACTH secretion from the pituitary gland, and decreased cortisol concentrations in healthy dogs. Therefore, the aim of this study was to investigate the therapeutic effects of CBX on dogs with PDH. Six dogs with PDH were treated with 60 to 80 mg/kg/day of CBX for 6 weeks, followed by trilostane, which is a commonly used agent for canine PDH. CBX treatment led to a gradual decrease in both basal and in corticotropic releasing hormone (CRH)-stimulated plasma ACTH concentrations and CRH-stimulated serum cortisol concentrations, without side effects. However, basal and stimulated ACTH and cortisol concentrations remained higher than those of healthy dogs, and clinical symptoms such as polydipsia and polyuria were not ameliorated. After a 2-week wash-out interval, trilostane was administered for 2 weeks. Although basal plasma ACTH concentrations were higher after trilostane treatment than CBX treatment, polydipsia and polyuria resolved in all six dogs. The reason for the lack of improvement in polydipsia and polyuria with CBX treatment is unclear. Other mechanisms, in addition to a partial decrease in ACTH secretion, are likely to be involved. In conclusion, this is the first study to report the in vivo effects of CBX in dogs with PDH. The findings suggest that CBX inhibits ACTH secretion from canine pituitary tumors, resulting in lower cortisol concentrations. PMID:27824928

  18. Disodium cromoglycate protects dystrophin-deficient muscle fibers from leakiness.

    PubMed

    Marques, Maria Julia; Ventura Machado, Rafael; Minatel, Elaine; Santo Neto, Humberto

    2008-01-01

    In dystrophin-deficient fibers of mdx mice and in Duchenne dystrophy, the lack of dystrophin leads to sarcolemma breakdown and muscle degeneration. We verified that cromolyn, a mast-cell stabilizer agent, stabilized dystrophic muscle fibers using Evans blue dye as a marker of sarcolemma leakiness. Mdx mice (n=8; 14 days of age) received daily intraperitoneal injections of cromolyn (50 mg/kg body weight) for 15 days. Untreated mdx mice (n=8) were injected with saline. Cryostat cross-sections of the sternomastoid, tibialis anterior, and diaphragm muscles were stained with hematoxylin and eosin. Cromolyn dramatically reduced Evans blue dye-positive fibers in all muscles (P<0.05; Student's t-test) and led to a significant increase in the percentage of fibers with peripheral nuclei. This study supports the protective effects of cromolyn in dystrophic muscles and further indicates its action against muscle fiber leakiness in muscles that are differently affected by the lack of dystrophin.

  19. Fospropofol disodium injection for the sedation of patients undergoing colonoscopy.

    PubMed

    Levitzky, Benjamin E; Vargo, John J

    2008-08-01

    Sedation plays a central role in making colonoscopy tolerable for patients and feasible for the endoscopist to perform. The array of agents used for endoscopic sedation continues to evolve. Fospropofol (FP), a prodrug of propofol with a slower pharmacokinetic profile, is currently under evaluation for use during endoscopic procedures. Preliminary data suggests that FP dosed at 6.5 mg/kg is well tolerated by most patients with perineal paresthesias being the most commonly experienced adverse effect. This article will examine the current literature on the use of FP for the sedation of patients undergoing colonoscopy, highlighting the pharmacokinetics, pharmacodynamics, risks, and common adverse events associated with the novel sedative/hypnotic.

  20. Fospropofol disodium injection for the sedation of patients undergoing colonoscopy

    PubMed Central

    Levitzky, Benjamin E; Vargo, John J

    2008-01-01

    Sedation plays a central role in making colonoscopy tolerable for patients and feasible for the endoscopist to perform. The array of agents used for endoscopic sedation continues to evolve. Fospropofol (FP), a prodrug of propofol with a slower pharmacokinetic profile, is currently under evaluation for use during endoscopic procedures. Preliminary data suggests that FP dosed at 6.5 mg/kg is well tolerated by most patients with perineal paresthesias being the most commonly experienced adverse effect. This article will examine the current literature on the use of FP for the sedation of patients undergoing colonoscopy, highlighting the pharmacokinetics, pharmacodynamics, risks, and common adverse events associated with the novel sedative/hypnotic. PMID:19209255

  1. Formulation of carbenoxolone for delivery to the skin.

    PubMed

    Hirata, Kazumasa; Helal, Fouad; Hadgraft, Jonathan; Lane, Majella E

    2013-05-20

    Carbenoxolone (CEX), a semi-synthetic derivative of glycyrrhetinic acid, has previously been used as a disodium salt for the management of dyspepsia and peptic ulcer because of its anti-inflammatory properties. Although glycyrrhetinic acid is available in pharmaceutical and personal care products for skin care, the topical use of the free acid form of CEX, has not previously been reported. In this work we investigated the percutaneous penetration of CEX. Solubility and permeability studies were conducted using a range of solvents or skin permeation enhancers (SPEs) commonly used for skin delivery. Binary combinations of dimethyl isosorbide (DMI) and Transcutol™ (TC) with isopropyl myristate (IPM) were effective in promoting skin permeation of CEX although individual solvents were not. Alternative fatty acid esters to IPM were subsequently investigated with the most promising formulation consisting of TC and propylene glycol laurate (PGL). Interestingly, propylene glycol monolaurate (PGML) did not demonstrate comparable efficacy when combined with TC. A ternary formulation consisting of TC, PGL and IPM demonstrated the best permeation enhancement of CEX compared with all other vehicles. The findings confirm (i) the feasibility of promoting CEX penetration across the skin (ii) the synergistic effect of combinations of solvents and SPEs on dermal and transdermal delivery (iii) the necessity for more fundamental studies to explain the differential effects of fatty acid esters on the skin barrier.

  2. [Difference of lung deposition rate of disodium cromoglycate (DSCG) among three kinds of electric nebulizer].

    PubMed

    Murayama, N; Kameda, M; Takamatsu, I; Inoue, T; Doi, S; Toyoshima, K

    1996-01-01

    We examined the lung deposition rate of DSCG with three kinds of electric nebulizer (NE-U03, Pari-Master, Nisshou) on 5 pediatrician skilled with inhalation therapy (31-54 years of age). Excretion of DSCG for 4 hours after inhalation in urine were highest in NE-U03 group, second in Pari-Master group and least in Nisshou group. And then we studied bronchodilating effect of sulbutamol on 18 children (7-17 years of age) with acute exacerbation of bronchial asthma with NE-U03 and Pari-Master. Asthmatic symptom score, SaO2 and pulmonary function were examined before and after inhalation. The delta %FVC, delta %FEV1.0, delta %PEF, delta %V50 and delta %V25 using NE-U03 were 10.3%, 19.1%, 25.5%, 32.5%, and 29.3% in NE-U03 group and 10.6%, 15.9%, 24.1%, 25.4% and 21.3% in Pari-Master group. The data of pulmonary obstraction in NE-03 group were better than that in Pari-Master group. From our data it is obvious that 3 kinds of electric nebulizers have different efficacy in regard to the lung deposition dose of inhaled drugs. When we compare the efficacy of drugs. When we compare the efficacy of drugs for nebulizer inhalation therapy, we should use the drug dose attained to lung and not nominal drug dose in principle.

  3. Disodium Cromoglycate, A Mast-Cell Stabilizer, Alters Postradiation Regional Cerebral Blood Flow in Primates

    DTIC Science & Technology

    1986-01-01

    Systemic blood pressures were determined si- multaneously. The data indicated that DSCG was successful in diminishing postra- diation decrease in cerebral...blood flow, Irradiated animals pretreated with DSCG , showed only a 10% decrease in hypothalamic blood flow 60 min postradiation, while untreated...irradiated animals showed’ a 57% decrease. The cortical blood flow of DSCG treated, irradiated animal ’Iweda triphasic response, with a decrease of 38

  4. [Effect of combination therapy with disodium cromoglycate (DSCG) and Ozagrel on non-atopic asthmatics].

    PubMed

    Yoshida, N; Suguro, H; Hashimoto, N; Majima, T; Yamaguchi, M; Horie, T

    1994-10-01

    Ozagrel (OKY-046), a selective inhibitor of thromboxane biosynthesis has been reported to reduce airway hyperresponsiveness in asthmatics. DSCG has been widely used for atopic, but not for non-atopic asthmatics. We evaluated the additive effect of combination therapy with DSCG and Ozagrel on nonatopic asthmatics. Fourteen asthmatics were divided into two groups. The patients in the O-D group were initially treated with Ozagrel (400 mg/day) for 4 weeks, and then DSCG (8 mg/day) was added for another 4 weeks. The patients in D-O group were initially treated with DSCG (8 mg/day), and then Ozagrel (400 mg/day) was added for 4 more weeks. TXB2, PGF2 alpha, PGE2, 6-keto-PGF1 alpha in sputum and 11-dehydro TXB2 in urine were measured before and after 4th and 8th weeks of therapy. Ozagrel decreased the metabolites of thromboxane and PGF2 alpha in sputum and urine. PGE2 in sputum tended to be increased by Ozagrel. DSCG did not affect mediators in sputum. Combination therapy with Ozagrel and DSCG showed the additive effect to single use on attack score and PF in non-atopic asthmatics.

  5. [Suppression of non-specific bronchial hyperreactivity by DSCG (Disodium cromoglycate) and ipratropium bromide (author's transl)].

    PubMed

    Götz, M; Popow, C

    1980-09-26

    The protective activity of DSCG was investigated in 18 children with established non-specific bronchial hyperreactivity induced by bronchial challenge with acetylcholine. Ipratropium bromide, the anticholinergic agent, was used for comparison. DSCG showed a statistically significant inhibitory action on the decrease in specific airway conductance. Besides the well-established inhibition of mast cell degranulation a direct action on cholinergic irritative receptors seems likely. Application of DSCG in immunologically ill-defined forms of bronchial asthma may be considered. As expected, the direct acetylcholine antagonist, ipratropium bromide, showed an overall protective effect.

  6. 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

  7. Pamidronate disodium for palliative therapy of feline bone-invasive tumors.

    PubMed

    Wypij, Jackie M; Heller, David A

    2014-01-01

    This study sought to quantify in vitro antiproliferative effects of pamidronate in feline cancer cells and assess feasibility of use of pamidronate in cats by assessing short-term toxicity and dosing schedule in cats with bone-invasive cancer. A retrospective pilot study included eight cats with bone invasive cancer treated with intravenous pamidronate. In vitro, pamidronate reduced proliferation in feline cancer cells (P < 0.05). One cat treated with pamidronate in combination with chemotherapy and two cats treated with pamidronate as a single agent after failing prior therapy had subjective clinically stable disease; median progression free interval in these cats from initial pamidronate treatment was 81 days. Three cats developed azotemia while undergoing various treatment modalities including nonsteroidal anti-inflammatory drugs and pamidronate. Median overall survival was 116.5 days for all cats and 170 days for cats with oral squamous cell carcinoma. Median progression free survival was 55 days for all cats and 71 days for cats with oral squamous cell carcinoma. Pamidronate therapy appears feasible for administration in cancer bearing cats with aggressive bone lesions in the dose range of 1-2 mg/kg every 21-28 days for multiple treatments. No acute or short-term toxicity was directly attributable to pamidronate.

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

    ClinicalTrials.gov

    2017-03-15

    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

  9. Chelatable lead body burden (by calcium-disodium EDTA) and blood lead concentration in man

    SciTech Connect

    Brangstrup Hansen, J.P.; Dossing, M.; Paulev, P.E.

    1981-01-01

    The chelatable part of lead body burden was measured in 32 workers and seven office workers after an infusion test with CaNa/sub 2/EDTA. The workers had been exposed to lead at a lead and zinc processing unit for one to three years (mean one year). There was good correlation (r = 0.87) between blood lead and chelatable urinary lead excretion described by the equation y = 0 07.10/sup 0.46 x/. From this equation it can be predicted that the generally accepted limit value for chelatable urinary lead excretion, 0.42 ..mu..mol/mmol CaNa/sub 2/EDTA administered per 24 hours (3.1 ..mu..mol/24 hours or 650 ..mu..g/24 hours), corresponds to a blood lead concentration (PbB) of 1.7 ..mu..mol/l (or 35 ..mu..g/100 ml), which is lower than the commonly accepted limit value of 2.9 ..mu..mol/1 (or 60..mu..g/100 ml) for occupationally lead-exposed persons. There was a better correlation between the chelatable lead excretion and the urinary ALA-excretion (r = 0.45; p < 0.001) than between PbB and the urinary ALA-excretion (r = 0.26; p > 0.05).

  10. Effect of oral calcium disodium EDTA on iron absorption in a human model of iron overdose.

    PubMed

    Matteucci, Michael J; Habibe, Michael; Robson, Kristie; Baldassano, Accursia A; Riffenburgh, Robert H; Tanen, David A

    2006-01-01

    Anecdotal case reports and animal models have suggested that the administration of CaNa2EDTA (EDTA) may be effective in reducing the absorption of iron after an oral iron overdose. We designed this study to determine the effect of orally administrated EDTA with or without activated charcoal (AC) on iron absorption after a mild iron ingestion in healthy human volunteers. A randomized, crossover study was conducted in eight healthy human volunteers. All subjects ingested 5 mg/kg of elemental iron in the form of ferrous sulfate. One hour post ingestion, subjects were randomized to receive 35 mg/kg EDTA, EDTA plus 50 grams of AC, or water. Serial iron levels were obtained at baseline and every hour for the first 6 hours, then at 8, 12, and 24 hours. A 2-week washout was used between study arms. The Kruskal-Wallis test was used for the following comparisons between treatment groups: baseline serum iron levels, area under time-concentration curves (AUCs) from baseline to 12 hours and baseline to 24 hours, and peak iron levels. Baseline serum iron levels did not differ among the three treatment groups (p = 0.844). AUCs were not different among groups (p = 0.746 for 12 hr, p = 0.925 for 24 hr). AUC medians (with 95% binomial confidence bounds) for control, EDTA, EDTA + AC groups, respectively, for 12 hr were: 2813 (2298, 3561), 2570 (1669, 3476), and 2654 (2125, 3600); and for 24 hr were: 4083 (3488,5314), 4139 (2666, 5547), and 4274 (3336, 5577). Peak serum iron levels did not differ among treatment groups (p = 0.481). Peak iron level medians in microg/dL (with 95% binomial confidence bounds) were for control: 329 (253, 382), for EDTA: 271 (184, 375), and for EDTA + AC: 285 (229, 352). Orally administered EDTA did not significantly reduce iron absorption when administered 1 hour post iron ingestion during the 12 or 24-hour period following the ingestion of 5 mg/kg of elemental iron in healthy human volunteers.

  11. Synthesis, Solution, and Structural Characterization of Tetrahydrofuranyl-2,2-Bisphosphonic Acid Disodium Salt

    PubMed Central

    Maltezou, Elena; Stylianou, Marios; Roy, Sudeshna; Drouza, Chryssoula; Keramidas, Anastasios D.

    2010-01-01

    Bisphosphonates are biologically relevant therapeutics for bone disorders and cancer. Reaction of γ-chlorobutyric acid, phosphorus acid, and phosphorus trichloride without the use of solvent gave the tetrahydrofuranyl-2,2-bisphosphonate sodium salt (Na2H2L). The Na2H2L was isolated, characterized in solution by 1H, 13C, and 31P NMR spectroscopy and in solid state by single X-Ray crystallography. The crystal structure showed that the Na2H2L forms in the crystal infinite two-dimensional sheets stacked one parallel to the other. A comparison of the chelating properties of H2L2− with similar hydroxyl bisphosphonate ligands shows that the strength of the Na–O(furanyl/hydroxyl) bond is directly related to the total charge of the ligand anion. PMID:20467558

  12. The poor bioavailability of elemental iron in corn masa flour is not affected by disodium EDTA.

    PubMed

    Walter, Tomas; Pizarro, Fernando; Boy, Erick; Abrams, Steven A

    2004-02-01

    The most sustainable way to eradicate iron deficiency is through food fortification. Elemental iron powders are commonly utilized as fortificants due to their low cost and few sensory problems. However, their bioavailability is unknown. Our goals were to measure the bioavailability of elemental iron in Mexican style corn masa flour tortillas and to evaluate the effects of Na(2)EDTA. We used a stable isotope of H(2)-reduced iron powder, with and without Na(2)EDTA in tortillas prepared with corn masa flour. Two groups of 5- to 7-y-old children (n = 12/group) were fed tortillas to which was added 3 mg/100 g of H(2)-reduced (58)Fe with a mean particle size of 15 micro m. In one group, Na(2)EDTA was incorporated at a ratio of 1:2 mol/mol. The next day, (57)Fe ascorbate was given as a reference dose. After 14 d, blood samples were analyzed for isotopic enrichment. When normalized to 40% absorption of the reference dose, the geometric mean (+/-range 1 SD) bioavailability of reduced iron in tortilla was 3.8% (2.7-5.3). The addition of Na(2)EDTA, tended to increase it (P = 0.18) to 5.1% (2.8-9.2). This observed low absorption was compounded by the use of iron isotopes with smaller particle size (mean diameter 15 micro m) than typical of commercial elemental iron powder (<45 micro m). We conclude that H(2)-reduced iron powder is an ineffective fortificant in corn tortillas.

  13. Iron bioavailability in corn-masa tortillas is improved by the addition of disodium EDTA.

    PubMed

    Walter, Tomás; Pizarro, Fernando; Olivares, Manuel

    2003-10-01

    Corn-masa flour flat bread tortillas are the main staple of Mexican and Central American populations. Due to high concentrations of inhibitors of iron absorption, the bioavailability from this matrix is unknown. We wanted to determine the most suitable fortificant that would efficaciously improve iron bioavailability. In tortillas prepared with commercial precooked, lime-treated, corn-masa flour, we examined the in vitro solubility of the following forms of iron: native iron with and without Na2EDTA, elemental reduced iron plus Na2EDTA, ferrous fumarate with and without Na2EDTA, bisglycine iron, ferrous sulfate and NaFeEDTA. We also examined the in vivo bioavailability in humans with double radioiron erythrocyte incorporation of ferrous fumarate with and without Na2EDTA, bisglycine iron, NaFeEDTA and native iron plus Na2EDTA, beans and rice. In vitro, solubility ranged from 1% in iron forms without Na2EDTA to 19.4% for NaFeEDTA. Forms of iron with Na2EDTA had intermediate values. In vivo radioiron studies showed that iron forms without Na2EDTA also had low bioavailability (< or =1%). NaFeEDTA had the highest bioavailability (5.3%). The bioavailability of all iron forms improved significantly when tested with Na2EDTA (<0.05). Adding Na2EDTA to ferrous fumarate increased bioavailability from 0.87% to 2.9% (P < 0.001). We conclude that NaFeEDTA is the form of iron best absorbed, but alternatively, ferrous fumarate plus Na2EDTA comprises a feasible option as a fortificant.

  14. Poly[[μ(10)-2,3-bis(carboxymethyl)butanedioato]disodium].

    PubMed

    Wu, Jiang; Zhu, Hong-Lin

    2010-10-20

    The asymmetric unit of the title compound, [Na(2)(C(8)H(8)O(8))](n), contains one Na(+) ion and half of a 2,3-bis(carboxymethyl)butanedioate (H(2)BTC(2-)) dianion, which lies on a center of symmetry. The dianion exhibits a μ(10)-bridging mode. Each Na atom lies in a NaO(6) octa-hedron defined by six O atoms from five dianions. Adjacent NaO(6) octa-hedra share a common O-O edge, generating a biocta-hedron; adjacent biocta-hedra are O-O edge-connected to one another, building up a chain along [001]. The chains are connected by adjacent H(2)BTC(2-) anions into a three-dimensional framework. The structure is further stabilized by O-H⋯O hydrogen bonds.

  15. 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 Pemetrexed Disodium and Cisplatin or Carboplatin

    ClinicalTrials.gov

    2017-08-17

    Advanced Malignant Solid Neoplasm; Advanced Peritoneal Malignant Mesothelioma; Advanced Pleural Malignant Mesothelioma; Recurrent Malignant Solid Neoplasm; Recurrent Peritoneal Malignant Mesothelioma; Recurrent Pleural Malignant Mesothelioma; Stage III Non-Small Cell Lung Cancer AJCC v7; Stage III Ovarian Cancer; Stage III Pleural Malignant Mesothelioma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer AJCC v7; Stage IV Ovarian Cancer; Stage IV Pleural Malignant Mesothelioma AJCC v7; Thymoma; Unresectable Solid Neoplasm

  16. Final report on the safety assessment of EDTA, calcium disodium EDTA, diammonium EDTA, dipotassium EDTA, disodium EDTA, TEA-EDTA, tetrasodium EDTA, tripotassium EDTA, trisodium EDTA, HEDTA, and trisodium HEDTA.

    PubMed

    Lanigan, Rebecca S; Yamarik, Torill A

    2002-01-01

    EDTA (ethylenediamine tetraacetic acid) and its salts are substituted diamines. HEDTA (hydroxyethyl ethylenediamine triacetic acid) and its trisodium salt are substituted amines. These ingredients function as chelating agents in cosmetic formulations. The typical concentration of use of EDTA is less than 2%, with the other salts in current use at even lower concentrations. The lowest dose reported to cause a toxic effect in animals was 750 mg/kg/day. These chelating agents are cytotoxic and weakly genotoxic, but not carcinogenic. Oral exposures to EDTA produced adverse reproductive and developmental effects in animals. Clinical tests reported no absorption of an EDTA salt through the skin. These ingredients are likely, however, to affect the passage of other chemicals into the skin because they will chelate calcium. Exposure to EDTA in most cosmetic formulations, therefore, would produce systemic exposure levels well below those seen to be toxic in oral dosing studies. Exposure to EDTA in cosmetic formulations that may be inhaled, however, was a concern. An exposure assessment done using conservative assumptions predicted that the maximum EDTA dose via inhalation of an aerosolized cosmetic formulation is below that shown to produce reproductive or developmental toxicity. Because of the potential to increase the penetration of other chemicals, formulators should continue to be aware of this when combining these ingredients with ingredients that previously have been determined to be safe, primarily because they were not significantly absorbed. Based on the available data, the Cosmetic Ingredient Review Expert Panel found that these ingredients are safe as used in cosmetic formulations.

  17. [A comparison of the pharmacological actions between DSCG (disodium cromoglycate) and BDP (beclomethasone dipropionate) in the treatment of bronchial asthma].

    PubMed

    Shida, T

    1996-11-01

    Effects and actions of DSCG and corticosteroids in the airways could not essentially evaluated at the same situation, before the inhaled BDP had been used. Each of the drugs have been shown to reduce both immediate and late phase responses in experimentally induced asthma, exercise induced bronchospasm, and bronchial hypersensitivity to histamine especially after the prolonged pretreatment of BDP. DSCG probably targets nonspecifically the surfaces of relevant cells including mast cells and eosinophils, but BDP are known to act specifically and/or nonspecifically on the gene transcription in the various types of cells including eosinophils, lymphocytes, and resident cells. Many informations on the systemic side effects of BDP will be still required.

  18. Effects of lodoxamide (LOD), disodium cromoglycate (DSCG) and N-acetyl-aspartyl-glutamate sodium salt (NAAGA) on ocular active anaphylaxis.

    PubMed

    Goldschmidt, P; Luyckx, J

    1996-04-01

    LOD, DSCG and NAAGA eye-drops were evaluated on experimentally-induced ocular active anaphylaxis in guinea pigs. Twelve animals per group were sensitized with egg albumin i.p. and challenged on the surface of the eye 14 days later. Two days before challenge, animals were treated with LOD, DSCG or NAAGA 4 times a day. Permeability indexes were calculated after intracardiac injection of Evans Blue. No effect on ocular active anaphylaxis was found with LOD nor with DSCG. NAAGA was able to significantly reduce blood-eye permeability indexes.

  19. [Protection against laryngotracheobronchial obstruction and anaphylaxis with ketotifen and DSCG (disodium chromoglycate) in patients with food allergy].

    PubMed

    De Luca, L

    1988-01-01

    The authors studied in 30 allergic children to foods the protection of fall of spirometric flow (FEV1) after food challenge, caused by ketotifen and DSCG. The first showed a greater number of total protection = 60% in comparison with DSCG = 53.3%. The supply of both drugs at the same time showed a great amplification of protective action: total protection 73.3%, partial 20%; amount of two protections = 93.3%.

  20. Crystal structure of disodium dicobalt(II) iron(III) tris­(orthophosphate) with an alluaudite-like structure

    PubMed Central

    Bouraima, Adam; Assani, Abderrazzak; Saadi, Mohamed; Makani, Thomas; El Ammari, Lahcen

    2015-01-01

    The title compound, Na2Co2Fe(PO4)3, was synthesized by a solid-state reaction. This new stoichiometric phase crystallizes in an alluaudite-like structure. In this structure, all atoms are in general positions except for four atoms which are located at the special positions of the C2/c space group. One Co atom, one P and one Na atom are all located on Wyckoff position 4e (2), while the second Na atom is located on an inversion centre 4a (-1). The other Co and Fe atoms occupy a general position with a statistical distribution. The open framework results from [(Co,Fe)2O10] units of edge-sharing [(Co,Fe)O6] octa­hedra, which alternate with [CoO6] octa­hedra that form infinite chains running along the [10-1] direction. These chains are linked together through PO4 tetra­hedra by the sharing of vertices so as to build layers perpendicular to [010]. The three-dimensional framework is accomplished by the stacking of these layers, leading to the formation of two types of tunnels parallel to [010] in which the Na+ cations are located, each cation being surrounded by eight O atoms. PMID:25995879

  1. Poly[[hexa-aqua-sesqui(μ-benzene-1,2,4,5-tetra-carboxyl-ato)dicopper(II)disodium] monohydrate].

    PubMed

    Camara, Magatte; Keita, Mohamed Fadel; Cisse, Cherif Cheikh Samsidine; Daiguebonne, Carole; Guillou, Olivier

    2014-08-01

    In the title compound, {[Cu2Na2(C10H2O8)1.5(H2O)6]·H2O} n , the Cu(2+) ion is hexa-coordinated by five O atoms from benzene-1,2,4,5-tetra-carboxyl-ate (btec(4-)) ligands and one water mol-ecule. The Na(+) ion is also hexa-coordinated, by four O atoms from btec(4-) ligands and two water mol-ecules. One of the two btec(4-) mol-ecules sits on a crystallographic inversion centre. CuO6 and NaO6 octa-hedra are connected, forming bi-dimensional layers. These layers, which extend parallel to the ac plane, are further inter-connected by μ10- or μ11-bridging btec(4-) ligands and by O-H⋯O hydrogen bonds, involving both btec(4-) ligands and water mol-ecules, forming a three-dimensional network.

  2. Urinary excretion of essential metals following intravenous calcium disodium edetate: an estimate of free zinc and zinc status in man.

    PubMed

    Powell, J J; Burden, T J; Greenfield, S M; Taylor, P D; Thompson, R P

    1999-06-30

    Ethylenediaminetetraacetic acid (EDTA) is a powerful metal chelating agent used in the treatment of lead poisoning. EDTA also binds strongly to other metals. Thus, following intravenous infusion of CaNa2EDTA in healthy subjects the urinary excretion of calcium, copper, iron, magnesium and zinc were assessed. CaNa2EDTA significantly increased the urinary excretion of all metals except magnesium with greatest increases for iron (x 3.8 above baseline) and zinc (x 22). In addition, an in vitro dialysis study with a simplified serum showed that zinc (4.1 X 10(-3) mumol/h) was taken up more rapidly than iron (2.9 X 10(-3) mumol/h) by EDTA. The degree of binding of iron and zinc by EDTA depends on two factors: namely, the affinity of EDTA for Zn2+ and Fe3+, and the levels of unbound hydrated Zn2+ and Fe3+ ('free' ions). Despite differences in the rate of chelation of Zn2+ and Fe3+ by EDTA we show that the measurements of (a) circulating free iron, from routine clinical measurements of transferrin bound iron, and (b) the ratio of zinc:iron excreted in urine could provide an estimate of circulating free zinc, and thereby of zinc status, in man. In addition, EDTA treatment should be evaluated for patients with iron overload.

  3. Quality of Life Outcomes with a Disodium EDTA Chelation Regimen for Coronary Disease: Results from the TACT Randomized Trial

    PubMed Central

    Mark, Daniel B.; Anstrom, Kevin J.; Clapp-Channing, Nancy E.; David Knight, J.; Boineau, Robin; Goertz, Christine; Rozema, Theodore C.; Liu, Diane M.; Nahin, Richard L.; Rosenberg, Yves; Drisko, Jeanne; Lee, Kerry L.; Lamas, Gervasio A.

    2014-01-01

    Background The NIH-funded Trial to Assess Chelation Therapy (TACT) randomized 1708 stable coronary disease patients age 50 or older who were at least 6 months post myocardial infarction (2003-2010) to 40 infusions of a multicomponent EDTA chelation solution or placebo. Chelation reduced the primary composite endpoint of mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (hazard ratio 0.82, 95% confidence interval 0.69-0.99, p=0.035). Methods and Results In a randomly selected subset of 911 patients, we prospectively collected a battery of QOL instruments at baseline and 6, 12, and 24 months post-randomization. The pre-specified primary QOL measures were the Duke Activity Status Index (DASI)(eTable 1) and the Medical Outcomes Study Short-Form 36 Mental Health Inventory (MHI-5). All comparisons were by intention-to-treat. Baseline clinical and QOL variables were well balanced in the 451 patients randomized to chelation and the 460 to placebo. The DASI improved in both groups over the first 6 months of therapy but we found no evidence for a treatment-related difference [mean difference (chelation-placebo) over follow-up 0.9 (95% CI -0.7 to 2.6, p=0.27)]. There was no statistically significant evidence of a treatment-related difference in the MHI-5 during follow-up (mean difference 1.0, 95% CI -0.1 to 2.0, p=0.08). None of the secondary QOL measures showed a consistent treatment-related difference. Conclusions In stable, predominantly asymptomatic coronary disease patients with a history of myocardial infarction, EDTA chelation therapy did not have a detectable effect on quality of life over two years of follow-up. PMID:24987051

  4. The effect of intravenous disodium ethylenediaminetetraacetic acid (EDTA) plus supportive multivitamin/trace mineral supplementation upon fasting serum calcium.

    PubMed

    McDonagh, E W; Rudolph, C J; Cheraskin, E

    1983-08-01

    A literature search disclosed only very limited published material suggesting that EDTA therapy when given slowly does not seem to derange serum calcium metabolism. This report summarizes the observations of eighty private practice patients treated with EDTA and supportive multivitamin/trace mineral supplementation and its effects upon serum calcium. The evidence indicates that, in general, this form of chelation therapy does not alter serum calcium concentration. Additionally, and perhaps more importantly, the evidence here suggests the so-called high normals declined slightly, the low normals rise slightly, and those in the intermediate range remain unchanged.

  5. 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.

  6. Lipid oxidation in fish oil enriched mayonnaise: calcium disodium ethylenediaminetetraacetate, but not gallic acid, strongly inhibited oxidative deterioration.

    PubMed

    Jacobsen, C; Hartvigsen, K; Thomsen, M K; Hansen, L F; Lund, P; Skibsted, L H; Hølmer, G; Adler-Nissen, J; Meyer, A S

    2001-02-01

    The antioxidative effects of gallic acid, EDTA, and extra emulsifier Panodan DATEM TR in mayonnaise enriched with 16% fish oil were investigated. EDTA reduced the formation of free radicals, lipid hydroperoxides, volatiles, and fishy and rancid off-flavors. The antioxidative effect of EDTA was attributed to its ability to chelate free metal ions and iron from egg yolk located at the oil-water interface. Gallic acid reduced the levels of both free radicals and lipid hydroperoxides but promoted slightly the oxidative flavor deterioration in mayonnaise and influenced the profile of volatiles. Gallic acid may therefore promote the decomposition of lipid hydroperoxides to volatile oxidation products. Addition of extra emulsifier reduced the lipid hydroperoxide levels but did not influence the level of free radicals or the oxidative flavor deterioration in mayonnaisse; however, it appeared to alter the profile of volatiles. The effect of the emulsifier on the physical structure and rheological properties depended on the presence of antioxidants.

  7. Site-specific drug delivery to the middle region of the small intestine by application of enteric coating with hypromellose acetate succinate (HPMCAS).

    PubMed

    Tanno, Fumié K; Sakuma, Shinji; Masaoka, Yoshie; Kataoka, Makoto; Kozaki, Toshio; Kamaguchi, Ryosei; Ikeda, Yutaka; Kokubo, Hiroyasu; Yamashita, Shinji

    2008-07-01

    Enteric coatings that deliver drugs to specific regions of the small intestine were examined. Hypromellose acetate succinate (HPMCAS) with different values of succinoyl group contents was used. Decreasing the succinoyl group content resulted in an increase in the pH at which HPMCAS started to dissolve. Drug-containing granules with or without enteric coating were prepared and their in vitro dissolution in a simulated intestinal fluid of pH 6.8 was examined. Granules coated with HPMCAS having the succinoyl group content of 6.2% showed a lag time of about 30 min, although drug release from granules without coating was completed within 20 min. The time lag and dissolution rate were extended and reduced, respectively, as the succinoyl group content was decreased. Rat experiments indicated that enteric-coated granules disintegrated and the bulk of the drugs was immediately released when the granules reached a specific site of the small intestine where the pH corresponded to the pH at which the enteric coating agent started to dissolve. Similar results were observed in monkey experiments. It was suggested that HPMCAS with the succinoyl group content of about 5% was suitable as an enteric coating agent for delivering drugs to the middle-to-lower region of the small intestine.

  8. 21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... essential oils, disodium inosinate, disodium guanylate, hydrolysates of animal or plant origin (such as hydrolyzed vegetable protein), oleoresins of spices, soy products, and spice extractives. Such food additives...

  9. 21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... essential oils, disodium inosinate, disodium guanylate, hydrolysates of animal or plant origin (such as hydrolyzed vegetable protein), oleoresins of spices, soy products, and spice extractives. Such food additives...

  10. Site-specific drug delivery to the middle-to-lower region of the small intestine reduces food-drug interactions that are responsible for low drug absorption in the fed state.

    PubMed

    Tanno, Fumié K; Sakuma, Shinji; Masaoka, Yoshie; Kataoka, Makoto; Kozaki, Toshio; Kamaguchi, Ryosei; Ikeda, Yutaka; Kokubo, Hiroyasu; Yamashita, Shinji

    2008-12-01

    Food-drug interactions may reduce the bioavailability of drugs taken after meals (negative food effects). We designed enteric-coated tablets that start to disintegrate when they reach the middle-to-lower region of the small intestine, and examined whether they could reduce negative food effects in dogs. Tablets containing trientine as a model drug were coated with hypromellose acetate succinate (HPMCAS) with various values of succinoyl group content. The time lag of drug dissolution from these enteric-coated tablets in simulated intestinal fluid of pH 6.8 increased as the succinoyl group content was decreased. The AUC of trientine after oral administration of its aqueous solution to fed dogs was one-eighth of that in fasted dogs. The low drug absorption in fed dogs was improved when trientine was administered as enteric-coated tablets. The average ratio of AUC in the fed state to that in the fasted state increased with decreasing succinoyl group content of HPMCAS. Negative food effects completely disappeared after oral administration of tablets coated with HPMCAS having a succinoyl group content of 6.2% or less, which probably disintegrated in the middle-to-lower small intestine. Our results indicated that food-drug interactions were avoided by separating the main absorption site of drugs from that of food components.

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

    ClinicalTrials.gov

    2017-09-12

    Metastatic Malignant Neoplasm in the Brain; Stage IIIA Large Cell Lung Carcinoma AJCC v7; Stage IIIA Lung Adenocarcinoma AJCC v7; Stage IIIA Non-Small Cell Lung Cancer AJCC v7; Stage IIIB Large Cell Lung Carcinoma AJCC v7; Stage IIIB Lung Adenocarcinoma AJCC v7; Stage IIIB Non-Small Cell Lung Cancer AJCC v7; Stage IV Large Cell Lung Carcinoma AJCC v7; Stage IV Lung Adenocarcinoma AJCC v7; Stage IV Non-Small Cell Lung Cancer AJCC v7

  12. Disodium cromoglycate (DSCG) selectively inhibits IgE production and enhances IgG4 production by human B cell in vitro.

    PubMed

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

    1991-06-01

    The effect of DSCG on human IgE production in vitro was studied. DSCG selectively inhibited interleukin-4 (IL-4) induced IgE production by mononuclear cells (MNC) from normal donors without affecting IgM, IgA, IgG1, IgG2 or IgG3 production. In contrast, DSCG enhanced IgG4 production. To achieve this effect, DSCG must be added to the culture at the initiation and be present throughout the entire culture period. Interferon-gamma (IFN-gamma) also inhibited IL-4-induced IgE production, but IgG4 production was not affected by IFN-gamma. Monoclonal anti-IFN-gamma antibody blocked the inhibition of IgE production by IFN-gamma, but did not block the inhibition of IgE production by DSCG. DSCG also selectively inhibited spontaneous IgE production and enhanced IgG4 production by B cells from atopic patients in the presence of T cells and monocytes. These results indicate that there is a mechanism of IgE production inhibition which is not mediated by IFN-gamma. We also found that DSCG is an excellent reagent for the study of IgE and IgG4 regulation in vitro.

  13. Disodium cromoglycate (DSCG) selectively inhibits IgE production and enhances IgG4 production by human B cell in vitro.

    PubMed Central

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

    1991-01-01

    The effect of DSCG on human IgE production in vitro was studied. DSCG selectively inhibited interleukin-4 (IL-4) induced IgE production by mononuclear cells (MNC) from normal donors without affecting IgM, IgA, IgG1, IgG2 or IgG3 production. In contrast, DSCG enhanced IgG4 production. To achieve this effect, DSCG must be added to the culture at the initiation and be present throughout the entire culture period. Interferon-gamma (IFN-gamma) also inhibited IL-4-induced IgE production, but IgG4 production was not affected by IFN-gamma. Monoclonal anti-IFN-gamma antibody blocked the inhibition of IgE production by IFN-gamma, but did not block the inhibition of IgE production by DSCG. DSCG also selectively inhibited spontaneous IgE production and enhanced IgG4 production by B cells from atopic patients in the presence of T cells and monocytes. These results indicate that there is a mechanism of IgE production inhibition which is not mediated by IFN-gamma. We also found that DSCG is an excellent reagent for the study of IgE and IgG4 regulation in vitro. PMID:1904324

  14. Dilithium disodium nickel(II) cyclo-hexa-phosphate dodeca-hydrate, Li(2)Na(2)NiP(6)O(18)·12H(2)O.

    PubMed

    Abid, Sonia; Al-Deyab, Salem S; Rzaigui, Mohamed

    2012-08-01

    The crystal structure of Li(2)Na(2)NiP(6)O(18)·12H(2)O is characterized by the presence of six-membered P(6)O(18) (6-) phosphate ring anions (inter-nal symmetry -1) having a chair conformation and three different cations, viz. Li(+), Na(+) and Ni(2+), to counterbalance the anionic charge. All atoms are in general positions except for nickel, which lies on a special position with site symmetry 2. Lithium has a tetra-hedral environment (LiO(4)), and sodium and nickel have octa-hedral environments [NaO(6) and Ni(H(2)O)(6), respectively]. The P(6)O(18) rings are linked via corner sharing by NaO(6) octa-hedra and LiO(4) tetra-hedra to form a three-dimensional framework presenting tunnels running along [010] in which the six-coordinated Ni(2+) cations are located. The structure is stabilized by a network of O-H⋯O hydrogen bonds.

  15. Atezolizumab, Pemetrexed Disodium, Cisplatin, and Surgery With or Without Radiation Therapy in Treating Patients With Stage I-III Pleural Malignant Mesothelioma

    ClinicalTrials.gov

    2017-09-04

    Stage I Pleural Malignant Mesothelioma AJCC v7; Stage IA Pleural Malignant Mesothelioma AJCC v7; Stage IB Pleural Malignant Mesothelioma AJCC v7; Stage II Pleural Malignant Mesothelioma AJCC v7; Stage III Pleural Malignant Mesothelioma AJCC v7

  16. Direct stability-indicating method development and validation for analysis of etidronate disodium using a mixed-mode column and charged aerosol detector.

    PubMed

    Liu, Xiao-Keng; Fang, Jiang B; Cauchon, Nina; Zhou, Pengzu

    2008-03-13

    This paper describes the development and validation of a rapid, direct, and stability-indicating method for analysis of etidronate, a bisphosphonate compound without a UV chromophore. A mixed-mode column was used to separate etidronate from its impurities in an 8-min gradient method and a charged aerosol detector (CAD) was used for detection. The developed HPLC method was validated with respect to specificity, linearity, accuracy, precision, sensitivity, and stability. The method can be used for release and stability testing of etidronate and has applicability to other similar bisphosphonate compounds.

  17. Poly[[hexa­aqua­sesqui(μ-benzene-1,2,4,5-tetra­carboxyl­ato)dicopper(II)disodium] monohydrate

    PubMed Central

    Camara, Magatte; Keita, Mohamed Fadel; Cisse, Cherif Cheikh Samsidine; Daiguebonne, Carole; Guillou, Olivier

    2014-01-01

    In the title compound, {[Cu2Na2(C10H2O8)1.5(H2O)6]·H2O}n, the Cu2+ ion is hexa­coordinated by five O atoms from benzene-1,2,4,5-tetra­carboxyl­ate (btec4−) ligands and one water mol­ecule. The Na+ ion is also hexa­coordinated, by four O atoms from btec4− ligands and two water mol­ecules. One of the two btec4− mol­ecules sits on a crystallographic inversion centre. CuO6 and NaO6 octa­hedra are connected, forming bi-dimensional layers. These layers, which extend parallel to the ac plane, are further inter­connected by μ10- or μ11-bridging btec4− ligands and by O—H⋯O hydrogen bonds, involving both btec4− ligands and water mol­ecules, forming a three-dimensional network. PMID:25249873

  18. Hypocalcemia induced by intravenous administration of disodium ethylenediaminotetraacetate and its effects on excretion of calcium in urine of cows fed a high chloride diet.

    PubMed

    Schonewille, J T; Van't Klooster, A T; Wouterse, H; Beynen, A C

    1999-06-01

    Evidence supports the theory that a diet that is rich in nonmetabolizable anions fed to dairy cows during the dry period reduces the risk of hypocalcemic paresis puerperalis. When cows are fed a diet that is rich in anions instead of cations, more Ca is absorbed in the intestine and excreted in urine. We hypothesized that, in cows fed a diet that was rich in anions, the increased flow of Ca through the body could be drained to support the maintenance of plasma Ca concentration around parturition. The hypothesis was tested by binding plasma Ca through intravenous administration of Na2-EDTA and measuring excretion of Ca in urine. In a 2-period x 14-d crossover study, six, nonpregnant, nonlactating, multiparous cows were fed either a diet that was rich in cations (dietary cation-anion difference = +332 meq/kg of dry matter) or rich in anions (dietary cation-anion difference = -230 meq/kg of dry matter). On the last day of each feeding period, Na2-EDTA was infused intravenously until the amount of plasma Ca that was not bound to EDTA reached approximately 1 mmol/L. The amount of EDTA that could be infused was significantly greater when the cows were fed the diet that was rich in anions. During the infusion of Na2-EDTA the rate of Ca excretion in urine dropped to almost 0 when the diet that was rich in anions was fed. After feeding the diet that was rich in cations, excretion of Ca in urine was negligible and was not reduced further by Na2-EDTA infusion. Thus, in cows fed a diet that was rich in anions, the Ca intended for excretion with urine can be used when plasma Ca is under stress as would occur at the onset of lactation. However, the amount of Ca derived from plasma, interstitial fluid, and the skeleton during Na2-EDTA infusion was quantitatively much more important to the supply of Ca than was the reduction in excretion of Ca in urine. Most likely, this relationship would also be true when the production of colostrum begins.

  19. Quality-of-life outcomes with a disodium EDTA chelation regimen for coronary disease: results from the trial to assess chelation therapy randomized trial.

    PubMed

    Mark, Daniel B; Anstrom, Kevin J; Clapp-Channing, Nancy E; Knight, J David; Boineau, Robin; Goertz, Christine; Rozema, Theodore C; Liu, Diane M; Nahin, Richard L; Rosenberg, Yves; Drisko, Jeanne; Lee, Kerry L; Lamas, Gervasio A

    2014-07-01

    The National Institutes of Health.funded Trial to Assess Chelation Therapy (TACT) randomized 1708 stablecoronary disease patients aged .50 years who were .6 months post.myocardial infarction (2003.2010) to 40 infusions ofa multicomponent EDTA chelation solution or placebo. Chelation reduced the primary composite end point of mortality,recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (hazard ratio, 0.82; 95%confidence interval, 0.69.0.99; P=0.035). In a randomly selected subset of 911 patients, we prospectively collected a battery of quality-of-life(QOL) instruments at baseline and at 6, 12, and 24 months after randomization. The prespecified primary QOL measures were the Duke Activity Status Index (Table I in the Data Supplement) and the Medical Outcomes Study Short-Form 36 Mental Health Inventory-5. All comparisons were by intention to treat. Baseline clinical and QOL variables were well balanced in the 451 patients randomized to chelation and in the 460 patients randomized to placebo. The Duke Activity Status Index improved in both groups during the first 6 months of therapy, but we found no evidence for a treatment-related difference (mean difference [chelation.placebo] during follow-up, 0.9 [95% confidence interval, .0.7 to 2.6; P=0.27]).There was no statistically significant evidence of a treatment-related difference in the Mental Health Inventory-5 during follow-up (mean difference, 1.0; 95% confidence interval, .0.1 to 2.0; P=0.08). None of the secondary QOL measures showed a consistent treatment-related difference. In stable, predominantly asymptomatic coronary disease patients with a history of myocardial infarction,EDTA chelation therapy did not have a detectable effect on QOL during 2 years of follow-up. URL: http://clinicaltrials.gov. Unique identifier: NCT00044213.

  20. A pH-stat study of the reaction of some transition metal cations with disodium ethylenedinitrilotetraacetate (EDTA) and its analytical application.

    PubMed

    Maccà, Carlo; Soldà, Lidia; Favaro, Gabriella; Pastore, Paolo

    2007-04-30

    The pH-stat titration technique is an autonomous and very powerful tool for performing and monitoring chelatometric titrations of metal cations with great accuracy, poorly known, however, and seldom exploited. Based on measurement of the amount of strong base required to keep the pH of the test solution at a selected value during stepwise known additions of ethylenedinitrilotetraacetate (EDTA), it requires a glass electrode as the only sensor and is easily implemented on potentiometric titrators. It was introduced a quarter of century ago on an empirical basis for a very peculiar purpose (determination of calcium in diary products), but only very recently it was generalised and its fundamentals were thoroughly examined. In this work, pH-static titrations of some transition metal cations of analytical relevance (Co(2+), Cu(2+), Mn(2+), Zn(2+)) were thoroughly investigated in the acid pH range between 2.3 and 5 or 7 (the highest pH depending on the metal hydroxide or carbonate solubility). The results at higher acidity showed unsuspected properties of such chelation reactions. At moderately acid pH (generally >/=4), indeed, pH-static titrations yield results of high precision and accuracy. On decreasing pH, however, the reaction stoichiomety deviates more and more from the 1:1 ratio between chelating agent and cation, seemingly because of formation of binuclear complexes, an occurrence very seldom mentioned in the current literature. The optimal titration conditions for each metal are defined, and directions for establishing a laboratory protocol for quantitative determinations are given.

  1. Poly[di-μ(2)-aqua-μ(5)-(pyridine-2,6-dicarboxyl-ato)-μ(3)-(pyridine-2,6-dicarboxyl-ato)-cobalt(II)disodium].

    PubMed

    Boyko, Alexander N; Golenya, Irina A; Izotova, Yulia A; Haukka, Matti; Prisyazhnaya, Elena V

    2011-12-01

    In the title compound, [CoNa(2)(C(7)H(3)NO(4))(2)(H(2)O)(2)](n), the Co(II) atom is coordinated by two pyridine N atoms and four carboxyl-ate O atoms from two doubly deprotonated pyridine-2,6-dicarboxyl-ate ligands in a distorted octa-hedral geometry. One Na(+) cation is coordinated by three carboxyl-ate O atoms and two water mol-ecules and the other is coordinated by five carboxyl-ate O atoms and two water mol-ecules in an irregular geometry. The bis-(pyridine-2,6-dicarboxyl-ato)cobalt complex units are connected by Na(+) cations and bridging water mol-ecules into a three-dimensional coordination network. O-H⋯O hydrogen bonds are formed between the water mol-ecules and the carboxyl-ate O atoms.

  2. A co-crystal of nona-hydrated disodium(II) with mixed anions from m-chloro-benzoic acid and furosemide.

    PubMed

    London, Bianca King; Claville, Michelle O Fletcher; Babu, Sainath; Fronczek, Frank R; Uppu, Rao M

    2015-10-01

    In the title compound, [Na2(H2O)9](C7H4ClO2)(C12H10ClN2O5S) {systematic name: catena-poly[[[triaquasodium(I)]-di-μ-aqua-[triaquasodium(I)]-μ-aqua] 3-chlorobenzoate 4-chloro-2-[(furan-2-ylmethyl)amino]-5-sulfamoylbenzoate]}, both the original m-chloro-benzoic acid and furosemide exist with deprotonated carboxyl-ates, and the sodium cations and water mol-ecules exist in chains with stoichiometry [Na2(OH2)9](2+) that propagate in the [-110] direction. Each of the two independent Na(+) ions is coordinated by three monodentate water mol-ecules, two double-water bridges, and one single-water bridge. There is considerable cross-linking between the [Na2(OH2)9](2+) chains and to furosemide sulfonamide and carboxyl-ate by inter-molecular O-H⋯O hydrogen bonds. All hydrogen-bond donors participate in a complex two-dimensional array parallel to the ab plane. The furosemide NH group donates an intra-molecular hydrogen bond to the carboxyl-ate group, and the furosemide NH2 group donates an intra-molecular hydrogen bond to the Cl atom and an inter-molecular one to the m-chloro-benzoate O atom. The plethora of hydrogen-bond donors on the cation/water chain leads to many large rings, up to graph set R 4 (4)(24), involving two chains and two furosemide anions. The chloro-benzoate is involved in only one R 2 (2)(8) ring, with two water mol-ecules cis-coordinated to Na. The furan O atom is not hydrogen bonded.

  3. 21 CFR 170.60 - Nitrites and/or nitrates in curing premixes.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... contain or constitute a source of secondary or tertiary amines, including but not limited to essential oils, disodium inosinate, disodium guanylate, hydrolysates of animal or plant origin (such as...

  4. 21 CFR 161.173 - Canned wet pack shrimp in transparent or nontransparent containers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... (vi) Flavorings. (vii) Sodium bisulfite. (viii) Calcium disodium EDTA (calcium disodium ethylene-diamine-tetra-acetate), complying with the provisions of § 172.120 of this chapter. (5) Labeling. (i) The...

  5. 21 CFR 161.173 - Canned wet pack shrimp in transparent or nontransparent containers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... (vi) Flavorings. (vii) Sodium bisulfite. (viii) Calcium disodium EDTA (calcium disodium ethylene-diamine-tetra-acetate), complying with the provisions of § 172.120 of this chapter. (5) Labeling. (i) The...

  6. A to Z List of Cancer Drugs

    MedlinePlus

    ... Aloxi (Palonosetron Hydrochloride) Ambochlorin (Chlorambucil) Amboclorin (Chlorambucil) Amifostine Aminolevulinic Acid Anastrozole Aprepitant Aredia (Pamidronate Disodium) Arimidex (Anastrozole) Aromasin ( ...

  7. 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.

  8. 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. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. 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.

  10. Di-μ-azido-bis­(μ-1,4,7,10,13,16-hexa­oxacyclo­octa­deca­ne)bis­(5,10,15,20-tetra­phenyl­porphyrinato)dicadmium­disodium

    PubMed Central

    Toumi, Hamza; Amiri, Nesrine; Belkhiria, Mohamed Salah; Daran, Jean-Claude; Nasri, Habib

    2012-01-01

    The asymmetric unit of the title compound, [Cd2Na2(N3)2(C44H28N4)2(C12H24O6)2], consists of one half of the dimeric complex; the tetra­nuclear mol­ecule lies about an inversion centre. The CdII atom is coordinated by the four pyrrole N atoms of the 5,10,15,20-tetra­phenyl­porphyrinate ligand and one N atom of the axial azide ligand in a square-pyramidal geometry. The azide group is also linked to the NaI atom, which is surrounded by one 18-crown-6 molecule and additionally bonded to a second 18-crown-6 molecule trans to the azide group. The porphyrin core exhibits a major doming distortion (∼40%) and the crystal structure is stabilized by weak C—H⋯π inter­actions. The mol­ecular structure features weak intra­molecular hydrogen bonds: two O—H⋯O inter­actions within the 18-crown-6 mol­ecule and one C—H(18-crown-6)⋯N(azido) contact. PMID:23468761

  11. Detection and characterization of small focal hepatic lesions (≤2.5 cm in diameter): a comparison of diffusion-weighted images before and after administration of gadoxetic acid disodium at 3.0T.

    PubMed

    Song, Kyoung Doo; Kim, Young Kon; Lee, Won Jae; Lee, Min Woo; Park, Min Jung; Hwang, Jiyoung; Lee, Mi Hee

    2012-06-01

    As diffusion-weighted imaging (DWI) is routinely incorporated into the standard clinical protocol, it is clinically relevant to determine whether DWI after gadoxetic acid is comparable to pre-contrast DWI, with regard to the detection and characterization of focal liver lesions. To compare DWI before and after administration of gadoxetic acid in the detection and characterization of small (≤2.5 cm) focal hepatic lesions. One hundred and fifty-eight patients with 237 focal hepatic lesions (≤2.5 cm) (124 HCCs, 50 metastases, 2 cholangiocarcinomas, 43 hemangiomas, and 18 cysts) were included. DWIs were obtained before and after administration of gadoxetic acid. Non-breath-hold DWI was performed with b values of 0, 100, and 800 s/mm(2). Signal-to-noise ratio (SNR), lesion-liver contrast-to-noise ratio (CNR), and apparent diffusion coefficients (ADCs) of the liver and lesion were calculated. Lesion detection with each DWI was evaluated with alternative free-response receiver-operating characteristic analysis by two observers. The sensitivity of the characterization of focal hepatic lesions as solid (malignancy) or non-solid (benignity) with each DWI was calculated using a five-point confidence scale. Inter-observer agreement regarding lesion detection and characterization was evaluated using kappa statistics. SNRs of the liver on post-contrast DWI were significantly lower than on unenhanced DWI at b = 800 s/mm(2) (P < 0.05). SNRs, CNRs, and ADCs of focal hepatic lesions were not significantly different between two DWIs (P > 0.05). The diagnostic accuracy (Az) for lesion detection and the sensitivity for lesion characterization did not show significant difference between two DWIs (P > 0.05). With regard to the detection and characterization of focal hepatic lesions, the kappa values for two DWIs indicated good and excellent inter-observer agreement, respectively. Gadoxetic acid-enhanced DWI showed comparable diagnostic capability to unenhanced DWI for the detection and characterization of small focal hepatic lesions.

  12. Application of a new mathematical method for the estimation of the mean surface area to calculate the percolation threshold of lobenzarit disodium [correction of dissodium] salt in controlled release matrices.

    PubMed

    Boza, Anailien; Blanquero, Rafael; Millan, Monica; Caraballo, Isidoro

    2004-07-01

    One of the practical handicaps for the application of the percolation theory to estimate the percolation threshold of drugs in controlled release systems is the fact that the dissolution studies must be carried out so that only one surface of the tablet is exposed to the dissolution medium. The aim of this work is to estimate the percolation threshold of the antiarthritic drug lobenzarit dissodium (LBD) in inert matrices prepared with the excipients Ethocel((R)) 100 and Eudragit((R)) RS-PO (10-75% w/w). Release assays were performed using the paddle method. The whole surface of the tablets was exposed to the dissolution medium. For the first time, a new mathematical method is developed to transform the amount of drug released in amount released per surface area in order to calculate the percolation thershold of LBD. The mathematical method proposed allows to calculate, using a new equation, the evolution of the mean surface area (O((t))). The new method was validated and three novel results were achieved: A constant value of (O((t))) at critical time (theta) in the matrices (O((theta))=1.272 cm(2)); a linear relationship between initial surface area (O((0))) and critical time; and a linear relationship between O((t)) and time. Employing the values of O((t)), it was possible to calculate for the first time, the percolation threshold (p(c1)) for LBD in Ethocel((R)) 100 (p(c1)=0.280+/-0.102) and Eudragit((R)) RS-PO (p(c1)=0.344+/-0.07) matrices.

  13. A combined approach to decrease the technological and sensory defects caused by fat and sodium reduction in Bologna-type sausages.

    PubMed

    Campagnol, Paulo Cezar Bastianello; Dos Santos, Bibiana Alves; Lorenzo, José Manuel; Cichoski, Alexandre José

    2017-09-01

    The effect of the addition of fructooligosaccharides, transglutaminase, disodium inosinate, and disodium guanylate on some technological and sensory parameters of low-fat and low-salt Bologna-type sausages was evaluated. In the first experiment, sausages with a 25% and 50% fat reduction containing 0, 3%, or 6% fructooligosaccharides were manufactured. Fat reduction adversely affected the emulsion stability, hardness, and sensory properties; however, the addition of 6% fructooligosaccharides reduced the loss of quality associated with a lower fat content. In the second experiment, sausages with a 50% fat reduction containing 6% fructooligosaccharides were produced. Additionally, the salt content was reduced by 50% and transglutaminase, disodium inosinate, and disodium guanylate were added. The combination of transglutaminase (1%), disodium inosinate (0.03%), and disodium guanylate (0.03%) was efficient to supress the technological and sensory defects caused by NaCl reduction in low-fat Bologna-type sausages.

  14. OPERATION GREENHOUSE. Scientific Director’s Report of Atomic Weapon Tests at Eniwetok, 1951. Annex 6.7. Contamination-Decontamination Studies

    DTIC Science & Technology

    1951-08-01

    and alkylidene materials. {d> Na-polyphos: Sodium hexametaphosphate (NauP.oO,,). <•> 2Na^ EDTA : The disodium salt of ethylene diamine tetraacetic... Disodium salt of ethylene diamine tetraacetic acid 1.0 Alrose Chemi- cal Co. 7 Ethomeen 18/25 Cationic Detergent 100 Tertiary amine with one...Complexing agent Na.jF.oO,, 17 Disodium ethylene diamine tetra- acetic acid Complexing agent 0.8 Acid purified and neutral- ized to diso

  15. 77 FR 50462 - Foreign-Trade Zone 59-Lincoln, NE, Notification of Proposed Production Activity; Novartis...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-21

    ...; rivastigmine hydrogen tartrate; tolnaftate (USP/EP); lansoprazole; loratadine; pyrilamine maleate (USP... extracts and similar thickeners; iron oxides and hydroxides; disodium carbonate; carbonates; flavoring...

  16. Dextrin-rhEGF conjugates as bioresponsive nanomedicines for wound repair.

    PubMed

    Hardwicke, Joseph; Ferguson, Elaine L; Moseley, Ryan; Stephens, Phil; Thomas, David W; Duncan, Ruth

    2008-09-24

    Growth factors are known to act in concert to promote wound repair, but their topical application rarely leads to a significant clinical improvement of chronic wounds due to premature inactivation in wound environment. The aim of this study was to synthesise a polymer-growth factor conjugate and investigate whether the novel concept called Polymer-masking-UnMasking-Protein Therapy (PUMPT) might be used to generate bioresponsive polymer therapeutics as nanomedicines able to promote tissue repair. Succinoylated dextrin ( approximately 85,000 g/mol; approximately 19 mol% succinoylation), and rhEGF were chosen as a first model combination. The conjugate synthesised contained approximately 16%wt rhEGF and <1% free protein. It exhibited increased stability towards proteolytic degradation by trypsin and the clinically relevant enzyme neutrophil elastase. The dextrin component was degraded on addition of alpha-amylase leading to sustained release of free rhEGF over time (52.7% release after 168 h). When biological activity was assessed (+/-alpha-amylase) in proliferation assays using epidermoid carcinoma (HEp2) cells and HaCaT keratinocytes, as anticipated, polymer conjugation reduced rhEGF bioactivity (p=0.0035). However, exposure to physiological concentrations of alpha-amylase triggered dextrin degradation and this led to protein unmasking with restoration of bioactivity to the level seen for unmodified rhEGF. Indeed, prolongation of HEp2 proliferation was observed over 8 days. The inability of dextrin, succinoylated dextrin or alpha-amylase alone to induce proliferative effects, and the ability of alpha-amylase-exposed dextrin-rhEGF to induce phosphorylation of the epidermal growth factor receptor (EGFR) in HEp2 cells confirmed a mechanism of action by stimulation of classical signal transduction pathways. These observations suggest that this dextrin-rhEGF, and other dextrin-growth factor conjugates have potential for further development as bioresponsive nanomedicines

  17. Problems in the production and use of 5 nm avidin-gold colloids.

    PubMed

    Morris, R E; Saelinger, C B

    1986-08-01

    Over the past 5 years we have encountered several problems in the production and use of 5 nm avidin-gold colloids for markers in electron microscopy. These problems include flocculation of colloids during reduction of chloroauric acid, insoluble gold pellets following ultracentrifugation, and non-specific binding of avidin-gold colloids to biological membranes. We are able to avoid these problems by: avoiding the use of crystalline chloroauric acid; succinoylating egg white avidin prior to adsorption on the gold sols; resuspending the pellets following ultracentrifugation in 5 mM phosphate buffer, pH 7.5; and using the avidin-gold colloids within 4 weeks of production.

  18. 21 CFR 169.115 - French dressing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... may be added in accordance with § 172.810 of this chapter. (9) Citric and/or malic acid, in an amount not greater than 25 percent of the weight of the acids of the vinegar or diluted vinegar calculated as acetic acid. (10) Sequestrant(s), including but not limited to calcium disodium EDTA (calcium disodium...

  19. 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- amino]phenyl](4...

  20. 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- amino]phenyl](4...

  1. 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- amino]phenyl](4...

  2. 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- amino]phenyl](4...

  3. 21 CFR 74.2101 - FD&C Blue No. 1.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...&C Blue No. 1 is principally the disodium salt of ethyl[4-[p-[ethyl(m-sulfobenzyl)amino]-α-(o... amounts of the isomeric disodium salts of ethyl[4-[p-[ethyl(p-sulfobenzyl)amino]-α-(o-sulfophenyl...-sulfobenzyl)amino]-α-(o-sulfophenyl)benzylidene]-2,5-cyclohexadien-1-ylidene](o-sulfobenzyl)ammonium hydroxide...

  4. Pediatric fatality secondary to EDTA chelation.

    PubMed

    Baxter, Arla J; Krenzelok, Edward P

    2008-12-01

    Chelation therapy has emerged as a popular treatment modality to remove heavy metals that are thought to cause autism. We report a fatality that occurred as a consequence of chelation therapy for autism when the incorrect form of EDTA was administered. A five-year-old autistic male was being chelated in a physician's office. While receiving his third treatment he went into cardiac arrest. It was not determined until after the child's death that he had been given edetate disodium rather than edetate calcium disodium, causing profound hypocalcemia and triggering the cardiac events that led to his death. In 1991, the CDC recommended using only edetate calcium disodium, not edetate disodium, to children because edetate disodium may induce tetany and possible hypocalcemia as illustrated in this case. The use of chelation therapy in autistic children has not been validated and can have tragic consequences.

  5. [Quality standards of effervescent granules for the treatment of cold pain].

    PubMed

    Sun, X; Zhang, Z; Liu, Z; Zhang, W

    1995-01-01

    Thin layer chromatography was performed to identify the ingredients of Effervescent Granules for arresting cold pain (Hantongding Paoteng Chongji). The limited doses of aconitine, granularity, moisture, acidity, sugar content, etc. were detected, and the contents of paeoniflorin, glycyrrhetinic acid and total alkaloids were determined. Thus, the quality standards for pharmaceutical preparation were preliminarily worked out.

  6. Selective solid-phase extraction of a triterpene acid from a plant extract by molecularly imprinted polymer.

    PubMed

    Claude, Bérengère; Morin, Philippe; Lafosse, Michel; Belmont, Anne-Sophie; Haupt, Karsten

    2008-04-15

    A molecularly imprinted polymer (MIP) has been prepared by a thermal polymerisation method using methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linking agent, chloroform as porogenic solvent and an oleanane triterpene compound (18-beta-glycyrrhetinic acid) as imprinted molecule (template). Equilibrium ligand binding experiments were done to assess the performance of the MIP relative to non-imprinted polymer (NIP). After optimisation of SPE protocol (CHCl3 as washing solvent and MeOH as elution solvent), successful imprinting was confirmed by comparison of the recoveries between NIP (5%) and MIP (97%) cartridges. The binding capacity of the MIP for 18-beta-glycyrrhetinic acid was determined to be 0.94 mg g(-1). Four structurally related oleanane triterpenes (18-alpha-glycyrrhetinic acid, oleanolic acid, echinocystic acid, erythrodiol) were selected to assess the MIP selectivity. Experimental data illustrated the influence of functional groups on the triterpene skeleton. The MIP was applied to the solid-phase extraction of triterpenoids from a plant extract prior HPLC analysis. However, CHCl3 was replaced by ACN during the washing step in order to suppress non-specific interactions due to polar matrix components. A selective extraction of 18-beta-glycyrrhetinic acid from hydrolyzed extract of liquorice roots was achieved with a good extraction yield (98%).

  7. Crystal structure of di-μ-chloro­acetato-hexa­kis­(di­methyl­formamide)­tetra­kis­(μ-N,2-dioxido­benzene-1-carboximidato)tetra­manganese(III)disodium dimethyl­formamide disolvate

    PubMed Central

    Daly, Connor I.; Zeller, Matthias; Zaleski, Curtis M.

    2014-01-01

    The synthesis, crystal structure, and FT–IR data for the title compound, [Na2Mn4(C2H2ClO2)2(C7H4NO3)4(C3H7NO)6]·2C3H7NO or Na2(O2CCH2Cl)2[12-MCMnIII N(shi)-4](DMF)6·2DMF, where MC is metallacrown, shi3− is salicyl­hydroximate, and DMF is N,N-di­methyl­formamide, is reported. The macrocyclic metallacrown consists of an –[MnIII—N—O]4– ring repeat unit and the metallacrown captures two Na+ ions in the central cavity above and below the plane of the metallacrown. Each Na+ ion is seven-coordinate and is bridged to two ring MnIII ions, through either a coordinating DMF mol­ecule or a chloro­acetate anion. The ring MnIII ions have either a tetra­gonally distorted octa­hedral geometry or a distorted square-pyramidal geometry. Weak C—H⋯O inter­actions, in addition to pure van der Waals forces, contribute to the overall packing of the mol­ecules. The complete molecule has inversion symmetry and is disordered over two sets of sites with an occupancy ratio of 0.8783 (7):0.1217 (7). The solvent molecule is also disordered over two sets of sites, with an occupancy ratio of 0.615 (5):0.385 (5). PMID:25552975

  8. 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

  9. Polymer masked-unmasked protein therapy. 1. Bioresponsive dextrin-trypsin and -melanocyte stimulating hormone conjugates designed for alpha-amylase activation.

    PubMed

    Duncan, Ruth; Gilbert, Helena R P; Carbajo, Rodrigo J; Vicent, María J

    2008-04-01

    Polymer-protein conjugation, particularly PEGylation, is well-established as a means of increasing circulation time, reducing antigenicity, and improving the stability of protein therapeutics. However, PEG has limitations including lack of polymer biodegradability, and conjugation can diminish or modify protein activity. The aim of this study was to explore a novel approach for polymer-protein modification called polymer-masking-unmasking-protein therapy (PUMPT), the hypothesis being that conjugation of a biodegradable polymer to a protein would protect it and mask activity in transit, while enabling controlled reinstatement of activity at the target site by triggered degradation of the polymeric component. To test this hypothesis, dextrin (alpha-1,4 polyglucose, a natural polymer degraded by alpha-amylase) was conjugated to trypsin as a model enzyme or to melanocyte stimulating hormone (MSH) as a model receptor-binding ligand. The effect of dextrin molecular weight (7700, and 47200 g/mol) and degree of succinoylation (9-32 mol %) on its ability to mask/unmask trypsin activity was assessed using N-benzoyl-L-arginine-p-nitroanilide (L-BAPNA). Dextrin conjugation reduced enzyme activity by 34-69% depending on the molecular weight and degree of succinoylation of dextrin. However, incubation with alpha-amylase led to reinstatement of activity to a maximum of 92-115%. The highest molecular dextrin (26 mol % succinoylation) gave optimum trypsin masking-unmasking. This intermediate was used to synthesize a dextrin-MSH conjugate (dextrin Mw = 47200 g/mol; MSH content 37 wt %), and its biological activity (+/-alpha-amylase) was assessed by measuring melanin production by murine melanoma (B16F10) cells. Conjugation reduced melanin production to 11%, but addition of alpha-amylase was able to restore activity to 33% of the control value. These were the first studies to confirm the potential of PUMPT for further application to clinically important protein therapeutics. The

  10. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ....2 percent. Higher sulfonated subsidiary colors (as sodium salts), not more than 1.0 percent. Lower sulfonated subsidiary colors (as sodium salts), not more than 1.0 percent. Disodium salt of 6-hydroxy-5-[(2...

  11. 75 FR 17142 - Determination of Regulatory Review Period for Purposes of Patent Extension; LUSEDRA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ... human drug product LUSEDRA (fospropofol disodium). LUSEDRA is a sedative-hypnotic agent indicated for... Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 355(i)) became effective: May 15, 2002. FDA has...

  12. Physical and Mechanical Properties and Fire, Decay, and Termite Resistance of Treated Oriented Strandboard

    DTIC Science & Technology

    2005-05-01

    mechanical properties and fire, decay, andtermite re- sistance of oriented strandboard (OSB) panels. Disodium octaborate tetrahydrate (DOT), boric acid ... Boric acid DOT MP BA/DOTb Content aBA = boric acid DOT = disodium octaborate tetrahydrate: MP =melamine phosphate. bHereafter these will be...mechanical and physical properties in medium den- sity fiberboard treated with zinc borate at retentions of 0.25, 0.5, 1, and 1.5 per- cent boric acid

  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, 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 dialkyl...

  14. 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 dialkyl...

  15. 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 dialkyl...

  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, 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 dialkyl...

  17. 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 dialkyl...

  18. 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.

  19. Mast Cell Stabilization Ameliorates Autoimmune Anti-Myeloperoxidase Glomerulonephritis

    PubMed Central

    Gan, Poh-Yi; O’Sullivan, Kim M.; Ooi, Joshua D.; Alikhan, Maliha A.; Odobasic, Dragana; Summers, Shaun A.; Kitching, A. Richard

    2016-01-01

    Observations in experimental murine myeloperoxidase (MPO)-ANCA-associated vasculitis (AAV) show mast cells degranulate, thus enhancing injury as well as producing immunomodulatory IL-10. Here we report that, compared with biopsy specimens from control patients, renal biopsy specimens from 44 patients with acute AAV had more mast cells in the interstitium, which correlated with the severity of tubulointerstitial injury. Furthermore, most of the mast cells were degranulated and spindle-shaped in patients with acute AAV, indicating an activated phenotype. We hypothesized that the mast cell stabilizer disodium cromoglycate would attenuate mast cell degranulation without affecting IL-10 production. We induced anti-MPO GN by immunizing mice with MPO and a low dose of anti-glomerular basement membrane antibody. When administered before or after induction of MPO autoimmunity in these mice, disodium cromoglycate attenuated mast cell degranulation, development of autoimmunity, and development of GN, without diminishing IL-10 production. In contrast, administration of disodium cromoglycate to mast cell-deficient mice had no effect on the development of MPO autoimmunity or GN. MPO-specific CD4+ effector T cell proliferation was enhanced by co-culture with mast cells, but in the presence of disodium cromoglycate, proliferation was inhibited and IL-10 production was enhanced. These results indicate that disodium cromoglycate blocks injurious mast cell degranulation specifically without affecting the immunomodulatory role of these cells. Thus as a therapeutic, disodium cromoglycate may substantially enhance the regulatory role of mast cells in MPO-AAV. PMID:26374606

  20. 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. © 2013 Asian Pacific Society of Nephrology.

  1. 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

    2013-10-07

    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.

  2. Development of a UPLC-TQ/MS Approach for the Determination of Eleven Bioactive Components in Haizao Yuhu Decoction Plus-Minus Haizao and Gancao Drug Combination after Oral Administration in a Rat Model of Hypothyroidism.

    PubMed

    Ma, Yingchang; Zhang, Yang; Zhai, Yuanjuan; Zhu, Zhenhua; Pan, Ying; Qian, Dawei; Su, Shulan; Fan, Xinsheng; Duan, Jinao

    2016-12-22

    Haizao Yuhu Decoction (HYD) has been used for approximately 500 years and is well-known in Traditional Chinese Medicine for its efficacy in the treatment of thyroid-related diseases. In this study, a rapid liquid chromatography-tandem mass spectrometry method was developed for the determination of liquiritin, naringin, hesperidin, peimine, liquiritigenin, glycyrrhizic acid, bergapten, nobiletin, osthole, and glycyrrhetinic acid in rat plasma to investigate the pharmacokinetic profile of different HYD prescriptions in a rat model of hypothyroidism. The differences in pharmacokinetic parameters among the groups were compared by Student's t-test. The pharmacokinetic profile of liquiritin, naringin, hesperidin, peimine, liquiritigenin, glycyrrhizic acid, bergapten, nobiletin, osthole, and glycyrrhetinic acid showed significant differences between Haizao and Gancao anti-drug combination and other herbs in HYD. These results may contribute to the rational clinical use of HYD and reveal the compatibility profile of the Haizao and Gancao anti-drug combination.

  3. Antimutagenic components in Glycyrrhiza against N-methyl-N-nitrosourea in the Ames assay.

    PubMed

    Inami, Keiko; Mine, Yusuke; Kojo, Yukiko; Tanaka, Satomi; Ishikawa, Satoko; Mochizuki, Masataka

    2017-03-01

    Antimutagenesis against N-nitroso compounds contribute to prevention of human cancer. We have found that Glycyrrhiza aspera ethanolic extract exhibits antimutagenic activity against N-methyl-N-nitrosourea (MNU) using the Ames assay with Salmonella typhimurium TA1535. In the present study, eight purified components from Glycyrrhiza, namely glabridin, glycyrrhetinic acid, glycyrrhizin, licochalcone A, licoricesaponin H2, licoricesaponin G2, liquiritigenin and liquiritin were evaluated for their antimutagenicity against MNU in the Ames assay with S. typhimurium TA1535. Glycyrrhetinic acid, glycyrrhizin, licoricesaponin G2, licoricesaponin H2 and liquiritin did not show the antimutagenicity against MNU in S. typhimurium TA1535. Glabridin, licochalcone A and liquiritigenin reduced revertant colonies derived from MNU in S. typhimurium TA1535 without showing cytotoxic effects, indicating that these compounds possess antimutagenic activity against MNU. The inhibitory activity of glabridin and licochalcone A was more effective than that of liquiritigenin. Thus, Glycyrrhiza contains antimutagenic components against DNA alkylating, direct-acting carcinogens.

  4. [Liquorice-induced hypertension and hypokalaemia].

    PubMed

    Nielsen, Mette Lundgren; Pareek, Manan; Andersen, Inger

    2012-04-09

    Consumption of large amounts of liquorice can cause hypertension and hypokalaemia. Liquorice contains glycyrrhetinic acid, which inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase type 2, and ultimately leads to an apparent mineralocorticoid excess syndrome. This case report describes a 50 year-old woman presenting with hypertension and hypokalaemia-induced limb paresis due to chronic liquorice ingestion. The patient was treated with potassium supplementation and spironolactone. Her blood pressure and electrolyte status normalised within a month after cessation of liquorice intake.

  5. Connexin 43 expression on peripheral blood eosinophils: role of gap junctions in transendothelial migration.

    PubMed

    Vliagoftis, Harissios; Ebeling, Cory; Ilarraza, Ramses; Mahmudi-Azer, Salahaddin; Abel, Melanie; Adamko, Darryl; Befus, A Dean; Moqbel, Redwan

    2014-01-01

    Eosinophils circulate in the blood and are recruited in tissues during allergic inflammation. Gap junctions mediate direct communication between adjacent cells and may represent a new way of communication between immune cells distinct from communication through cytokines and chemokines. We characterized the expression of connexin (Cx)43 by eosinophils isolated from atopic individuals using RT-PCR, Western blotting, and confocal microscopy and studied the biological functions of gap junctions on eosinophils. The formation of functional gap junctions was evaluated measuring dye transfer using flow cytometry. The role of gap junctions on eosinophil transendothelial migration was studied using the inhibitor 18-a-glycyrrhetinic acid. Peripheral blood eosinophils express Cx43 mRNA and protein. Cx43 is localized not only in the cytoplasm but also on the plasma membrane. The membrane impermeable dye BCECF transferred from eosinophils to epithelial or endothelial cells following coculture in a dose and time dependent fashion. The gap junction inhibitors 18-a-glycyrrhetinic acid and octanol did not have a significant effect on dye transfer but reduced dye exit from eosinophils. The gap junction inhibitor 18-a-glycyrrhetinic acid inhibited eosinophil transendothelial migration in a dose dependent manner. Thus, eosinophils from atopic individuals express Cx43 constitutively and Cx43 may play an important role in eosinophil transendothelial migration and function in sites of inflammation.

  6. 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.

  7. Hygroscopic behavior of atmospherically relevant water-soluble carboxylic salts and their influence on the water uptake of ammonium sulfate

    NASA Astrophysics Data System (ADS)

    Wu, Z. J.; Nowak, A.; Poulain, L.; Herrmann, H.; Wiedensohler, A.

    2011-12-01

    The hygroscopic behavior of atmospherically relevant water-soluble carboxylic salts and their effects on ammonium sulfate were investigated using a hygroscopicity tandem differential mobility analyzer (H-TDMA). No hygroscopic growth is observed for disodium oxalate, while ammonium oxalate shows slight growth (growth factor = 1.05 at 90%). The growth factors at 90% RH for sodium acetate, disodium malonate, disodium succinate, disodium tartrate, diammonium tartrate, sodium pyruvate, disodium maleate, and humic acid sodium salt are 1.79, 1.78, 1.69, 1.54, 1.29, 1.70, 1.78, and 1.19, respectively. The hygroscopic growth of mixtures of organic salts with ammonium sulfate, which are prepared as surrogates of atmospheric aerosols, was determined. A clear shift in deliquescence relative humidity to lower RH with increasing organic mass fraction was observed for these mixtures. Above 80% RH, the contribution to water uptake by the organic salts was close to that of ammonium sulfate for the majority of investigated compounds. The observed hygroscopic growth of the mixed particles at RH above the deliquescence relative humidity of ammonium sulfate agreed well with that predicted using the Zdanovskii-Stokes-Robinson (ZSR) mixing rule. Mixtures of ammonium sulfate with organic salts are more hygroscopic than mixtures with organic acids, indicating that neutralization by gas-phase ammonia and/or association with cations of dicarbonxylic acids may enhance the hygroscopicity of the atmospheric particles.

  8. Confirmation of PM typing protocols for consistent and reliable results.

    PubMed

    Crouse, C A; Nippes, D C; Ritzline, E L

    1996-05-01

    A recent report in the Perkin Elmer "Forensic Forum" bulletin described a modification to the previously published PM typing protocol indicating that in order to obtain consistent and reliable PM and DQA1 typing results, disodium EDTA should be added to the post-amplification mixture before denaturation of the DNA fragments. The analysis and validation of this suggestion is described in the accompanying paper. We report the evaluation of this additional step when typing for PM alleles and conclude that the standard operating procedures currently enforced at the Palm Beach County Sheriff's Office and Indian River crime laboratories do not necessitate the need for the addition of disodium EDTA to the PM amplified products prior to the heat denaturation step. Further, depending on an individual laboratory's PM protocol, the recommendation by Perkin Elmer to add disodium EDTA to PM amplified products before typing has merit and should be carefully considered when determining laboratory PM typing protocols.

  9. Synthesis of isomeric isothiazolo[4',3':4,5]- and isothiazolo[4',5':4,5]thieno[3,2-b]pyrano[2,3-d]pyridines by combination of domino reactions.

    PubMed

    Shestopalov, Anatoliy M; Larionova, Natalia A; Fedorov, Alexander E; Rodinovskaya, Lyudmila A; Mortikov, Valery Yu; Zubarev, Andrey A; Bushmarinov, Ivan S

    2013-10-14

    Isothiazolothienopyridines have been prepared by a domino reaction (the SN2 reaction → the Thorpe-Ziegler reaction → the Thorpe-Guareschi reaction type) from disodium 4-cyanoisothiazole-3,5-dithiolate. By changing the order of addition of the alkylation reagents in the reaction with disodium 4-cyanoisothiazole-3,5-dithiolate both possible isomers of the isothiazolothienopyridines are synthesized. These isomers were further used in three-component domino reaction (the Knoevenagel reaction → the Michael reaction → the hetero-Thorpe-Ziegler reaction type) to obtain wide range of isomeric isothiazolothienopyranopyridines.

  10. Ethylenediaminetetraacetic acid in endodontics

    PubMed Central

    Mohammadi, Zahed; Shalavi, Sousan; Jafarzadeh, Hamid

    2013-01-01

    Ethylenediaminetetraacetic acid (EDTA) is a chelating agent can bind to metals via four carboxylate and two amine groups. It is a polyamino carboxylic acid and a colorless, water-soluble solid, which is widely used to dissolve lime scale. It is produced as several salts, notably disodium EDTA and calcium disodium EDTA. EDTA reacts with the calcium ions in dentine and forms soluble calcium chelates. A review of the literature and a discussion of the different indications and considerations for its usage are presented. PMID:24966721

  11. Ethylenediaminetetraacetic acid in endodontics.

    PubMed

    Mohammadi, Zahed; Shalavi, Sousan; Jafarzadeh, Hamid

    2013-09-01

    Ethylenediaminetetraacetic acid (EDTA) is a chelating agent can bind to metals via four carboxylate and two amine groups. It is a polyamino carboxylic acid and a colorless, water-soluble solid, which is widely used to dissolve lime scale. It is produced as several salts, notably disodium EDTA and calcium disodium EDTA. EDTA reacts with the calcium ions in dentine and forms soluble calcium chelates. A review of the literature and a discussion of the different indications and considerations for its usage are presented.

  12. A synchrotron radiation study of the one-dimensional complex of sodium with (1S)-N-carboxyl­ato-1-(9-deaza­adenin-9-yl)-1,4-dide­oxy-1,4-imino-d-ribitol, a member of the ’immucillin’ family

    PubMed Central

    Gainsford, Graeme J.; Furneaux, Richard H.; Tyler, Peter C.; Sauve, Anthony; Shramm, Vern L.

    2010-01-01

    The sodium salt of [immucillin-A–CO2H]− (Imm-A), namely catena-poly[[[triaqua­disodium(I)](μ-aqua)[μ-(1S)-N-car­box­yl­ato-1-(9-deaza­adenin-9-yl)-1,4-dide­oxy-1,4-imino-d-ribi­tol][triaqua­disodium(I)][μ-(1S)-N-carboxyl­ato-1-(9-deaza­aden­in-9-yl)-1,4-dide­oxy-1,4-imino-d-ribitol

  13. [Extraction technology of effervescent granules for arresting cold pain optimized by orthogonal tests].

    PubMed

    Sun, X; Zhang, Z; Ma, L; Zhang, W

    1996-03-01

    In the extraction technology of Effervescent Granules for Arresting Cold Pain (Hantongding Paoteng Chongji), the drug combinative modes, solvent pH and drug granularity were optimized by orthogonal tests, with the total alkaloid, paeoniflorin and glycyrrhetinic acid as indexes. The experimental results show that it is better to decoct together all the recipe ingredients, with water of pH2 for the first decoction, then water of pH8 for the second decoction, and to make its granularities ranging from the original herbal pieces to particles which can pass through a No. 2 sieve.

  14. Comparative analysis of antibacterial properties and chemical composition of Glycyrrhiza glabra L. from Astrakhan region (Russia) and Calabria region (Italy).

    PubMed

    Astaf'eva, O V; Sukhenko, L T

    2014-04-01

    We compared antibacterial activity of various extracts of two licorice subspecies against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. Diethyl carbonate extracts of Glycyrrhiza glabra root from Astrakhan region (Russia) exhibited maximum activity against the test microbial strains; activity of Astrakhan licorice was superior among 50% ethanol extracts from Astrakhan (Russia) and Calabria (Italy). Antibacterial activity is directly proportional to the content of glycyrrhizin and 18β-glycyrrhetinic acid in the extracts. According to preliminary data, the content of these chemical components in Glycyrrhiza glabra root from Astrakhan region is higher than in licorice growing in Italy, which is presumably related to climate and geographic characteristics of Astrakhan region.

  15. Chromatography of crotamiton and its application to the determination of active ingredients in ointments.

    PubMed

    Izumoto, S; Machida, Y; Nishi, H; Nakamura, K; Nakai, H; Sato, T

    1997-06-01

    Crotamiton, which is a mixture of cis and trans isomers, was investigated by several separation techniques. One of the HPLC modes, in which crotamiton eluted as a single peak, was selected for the determination of five active ingredients (crotamiton, prednisolone, glycyrrhetinic acid, dibucaine and chlorhexidine hydrochloride) in an ointment. The simultaneous determination was performed using isocratic reversed-phase mode within 20 min by employing an octyl (C8) column and a mobile phase containing sodium dodecyl sulfate (SDS) and 2-propanol. The method was successfully applied to quality control and stability testing of the ointment.

  16. Inhibition of human enterovirus 71 replication by pentacyclic triterpenes and their novel synthetic derivatives.

    PubMed

    Zhao, Chun-hui; Xu, Jie; Zhang, Ying-qiu; Zhao, Long-xuan; Feng, Bin

    2014-01-01

    A large number of bioactive pentacyclic triterpenoids have been shown to have multiple biological activities. This study was conducted to evaluate the inhibitory activities of 6 newly synthesized and novel pentacyclic triterpenoids against enterovirus 71 (EV71). The parent compound, ursolic acid (UA), showed the greatest inhibitory activity against EV71, while oleanolic acid (OA), asiatic acid (AA), and synthetic derivatives of 18-β-glycyrrhetinic acid (GA) and OA also exhibited inhibitory effects, although to lesser extents. The results suggest these compounds show potential for further optimization as antiviral candidates for treatment of EV71 infections.

  17. 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 additive...

  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... more than 14.0 percent. Water-insoluble matter, not more than 0.2 percent. Higher sulfonated subsidiary...-naphthalenesulfonic acid, not more than 1.0 percent. Sodium salt of 6-hydroxy-2-naphthalenesulfonic acid (Schaeffer's...

  19. A commercial application of fire retardants to dry-formed hardboards

    Treesearch

    Gary C. Meyers; Carlton A. Holmes

    1977-01-01

    Based on laboratory performance with a number of fire-retardant chemicals, disodium octaborate tetrahydrate-boric acid and dicyandiamide-phosphoric acid-formaldehyde were selected for treating fiber and making 4 foot by 8-foot dry-formed hardboards on a commercial production line. The boards were evaluated for performance under exposure to fire, strength, dimensional...

  20. 21 CFR 74.1322 - D&C Red No. 22.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... The fluorescein is manufactured by the acid condensation of resorcinol and phthalic acid or its... soduim salts), not more than 10 percent. Water-insoluble matter not more than 0.5 percent. Disodium salt of phthalic acid, not more than 1 percent. Sodium salt of 2-(3,5-Dibromo-2,4-dihydroxybenzoyl)benzoic...

  1. Operational Environmental Assessment

    DTIC Science & Technology

    1988-09-01

    Benzene 35,500 ml Antimony Potassium Tartrate 4,000 gm Barbituric Acid 150 gm Barbituric Acid 400 gm Chromium Trioxide 6,000 gm Disodium Ethylenediamine...gin Cadmium Chloride 2,500 gin Potassium Phosphate Crystal 5,500 gin Carbon, Activated 5 lb 4- Picoline 500 gin HEPES 30 gin Ethylenediamine 15,000 ml

  2. 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.

  3. 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…

  4. Performance Characteristics of Borate Fatty Acid Formulations as Mold Inhibitors

    Treesearch

    Robert D. Coleman; Vina Yang; Carol A. Clausen

    2013-01-01

    The combination of boric acid (BA) or disodium octaborate tetrahydrate (DOT) and a fatty acid (FA) such as heptanoic, octanoic, and nonanoic acids (C7–C9) is an effective treatment solution for protecting wood structures against mold. BA or DOT alone have substantial potency against insects and decay fungi, but have negligible or no mold inhibitor activity. However,...

  5. Fire and bending properties of blockboard with fire retardant treated veneers

    Treesearch

    T. Laufenberg; N. Ayrilmis; R. White

    2006-01-01

    This study evaluated fire and bending properties of blockboards with various fire retardant treated veneers. Blockboards were manufactured using untreated fir strips and sandwiched between treated ekaba veneers at final assembly. The veneers were treated with either boric acid (BA), disodium octoborate tetrahydrate (DOT), alumina trihydrate (ATH), or a BA/DOT mixture....

  6. 21 CFR 150.161 - Artificially sweetened fruit preserves and jams.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... compensates for deficiency, if any, of the natural acidity of the fruit ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium... exceeding 2 ounces avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an...

  7. 21 CFR 150.161 - Artificially sweetened fruit preserves and jams.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... compensates for deficiency, if any, of the natural acidity of the fruit ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium... exceeding 2 ounces avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an...

  8. 21 CFR 150.141 - Artificially sweetened fruit jelly.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... deficiency, if any, of the natural acidity of the fruit juice ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium tartrate... avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an amount not exceeding 8...

  9. 21 CFR 150.161 - Artificially sweetened fruit preserves and jams.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... compensates for deficiency, if any, of the natural acidity of the fruit ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium... exceeding 2 ounces avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an...

  10. 21 CFR 150.141 - Artificially sweetened fruit jelly.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... deficiency, if any, of the natural acidity of the fruit juice ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium tartrate... avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an amount not exceeding 8...

  11. 21 CFR 150.141 - Artificially sweetened fruit jelly.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... deficiency, if any, of the natural acidity of the fruit juice ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium tartrate... avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an amount not exceeding 8...

  12. 21 CFR 150.161 - Artificially sweetened fruit preserves and jams.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... compensates for deficiency, if any, of the natural acidity of the fruit ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium... exceeding 2 ounces avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an...

  13. 21 CFR 150.141 - Artificially sweetened fruit jelly.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... deficiency, if any, of the natural acidity of the fruit juice ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium tartrate... avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an amount not exceeding 8...

  14. 21 CFR 150.141 - Artificially sweetened fruit jelly.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... deficiency, if any, of the natural acidity of the fruit juice ingredient. (3) Sodium citrate, sodium acetate, sodium tartrate, monosodium phosphate, disodium phosphate, trisodium phosphate, sodium potassium tartrate... avoirdupois per 100 pounds of the finished food. (4) Sodium hexametaphosphate in an amount not exceeding 8...

  15. 21 CFR 169.150 - Salad dressing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... sulfosuccinate may be added in accordance with § 172.810 of this chapter. (6) Citric and/or malic acid may be used in an amount not greater than 25 percent of the weight of the acids of the vinegar or diluted vinegar calculated as acetic acid. (7) Sequestrant(s), including but not limited to calcium disodium EDTA...

  16. Physical and mechanical properties and fire, decay, and termite resistance of treated oriented strandboard

    Treesearch

    Nadir Ayrilmis; S Nami Kartal; Theodore L. Laufenberg; Jerrold E. Winandy; Robert H. White

    2005-01-01

    This study evaluated the effects of a number of chemicals on the physical and mechanical properties and fire, decay, and termite resistance of oriented strandboard (OSB) panels. Disodium octaborate tetrahydrate (DOT), boric acid (BA), melamine phosphate (MP), and a BA/DOT mixture were sprayed onto the furnish at varying concentrations. The panels were tested for...

  17. 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 an...

  18. 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) Color...

  19. 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. 3-Hydroxy-2...

  20. 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 an...

  1. 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 3-hydroxy-2...

  2. 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 an...

  3. 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 3-hydroxy-2...

  4. 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 an...

  5. 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. 3-Hydroxy-2...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 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) Color...

  7. 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) Color...

  8. 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 an...

  9. Bisphosphonate-Based Contrast Agents for Radiological Imaging of Microcalcifications

    DTIC Science & Technology

    2006-03-01

    treatment of patients with bone metastases [5]. Two such commercially available compounds are pamidronate disodium, available as Aredia® from...reaction has superior yield (>70%) to the 18-21% yield for pamidronate - IRDye-78 (LI-COR) conjugation reported previously [6]. Representative images are

  10. Structures and Absolute Configurations of Sulfate-Conjugated Triterpenoids Including an Antifungal Chemical Defense of the Green Macroalga Tydemania expeditionis

    PubMed Central

    Jiang, Ren-Wang; Lane, Amy L.; Mylacraine, Lauren; Hardcastle, Kenneth I.; Fairchild, Craig R.; Aalbersberg, William; Hay, Mark E.; Kubanek, Julia

    2012-01-01

    Cytotoxicity-guided fractionation of the green macroalga Tydemania expeditionis led to isolation of four sulfate-conjugated triterpenoids including one new lanostane-type triterpenoid disulfate, lanosta-8-en-3,29-diol-23-oxo-3,29-disodium sulfate (1), and three known cycloartane-type triterpenoid disulfates, cycloartan-3,29-diol-23-one 3,29-disodium sulfate (2), cycloart-24-en-3,29-diol-23-one 3,29-disodium sulfate (3), and cycloartan-3,23,29-triol 3,29-disodium sulfate (4). Extensive 1D and 2D NMR analyses in combination with X-ray crystallography established the structure and absolute configuration of 1 and allowed determination of the absolute configurations of 2–4 with a revision of previously assigned configuration at C-5. Each natural product was moderately cytotoxic in tumor cell and invertebrate toxicity assays. Of the natural products, only 4 exhibited significant antifungal activity at whole-tissue natural concentrations against the marine pathogen Lindra thalassiae. Comparison of the biological activities of natural products with their desulfated derivatives indicated that sulfation does not appear to confer cytotoxicity or antifungal activity. PMID:18763828

  11. 21 CFR 177.1655 - Polysulfone resins.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... (CAS Reg. No. 25154-01-2) consisting of basic resins produced when the disodium salt of 4,4... with the solvents—distilled water, 50 percent (by volume) ethyl alcohol in distilled water, 3 percent acetic acid in distilled water, and n-heptane, yield total extractives in each extracting solvent not to...

  12. Effect of optical sensitisation on a surface plasmon resonance

    SciTech Connect

    Vinogradov, S V; Kononov, M A; Savranskii, V V; Valyanskii, S I; Urbaitis, M F

    2003-08-31

    A change in the excitation angle of surface plasmons is found in a three-layer thin-film Ag - Al{sub 2}O{sub 3} - AgI structure upon its optical sensitisation with the Arsenazo III dye [2,7-Bis(2-arsonophenylazo)chromotropic acid Disodium salt]. (special issue devoted to the memory of academician a m prokhorov)

  13. Laboratory evaluation of borate:amine:copper derivatives In wood for fungal decay protection

    Treesearch

    George Chen

    2011-01-01

    This study aimed to evaluate borate:amine:copper derivatives in wood for fungal decay protection as well as the permanence of copper and boron in wood. Each of four derivatives of borate:amine:copper prevented fungal decay in wood. Disodium tetraborate decahydrate (borax):amine:copper derivatives with 0.61-0.63% retention after water leaching prevented decay by...

  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. Corrosion Mechanism of Cu-9.4 Ni-1.7 Fe Alloy in 3.4 WT.% NaCl Solution with and without Sulfide Contamination.

    DTIC Science & Technology

    1981-08-03

    200 ml of 10 M NaOH, 35 g ascorbic acid, 67 g disodium EDTA , and about 800 ml distilled water) was always added to the sulfide standard and ensured...flow 2 meter. The H2 gas was dried by Drierite (anhydrous calcium sulfate) and magnesium perchlorate followed by a magnesium trap heated to 673 K to

  16. Evaluation of the double-disk synergy test for New Delhi metallo-β-lactamase-1 and other metallo-β-lactamase producing gram-negative bacteria by using metal-ethylenediaminetetraacetic acid complexes.

    PubMed

    Fujisaki, Momoko; Sadamoto, Shinya; Hishinuma, Akira

    2013-05-01

    New Delhi metallo-β-lactamase-1 (NDM-1), one of the metallo-β-lactamases (MBLs), has been identified from clinical isolates worldwide. Rapid detection of NDM-1 producers is necessary to prevent their dissemination. Seven types of EDTA complexes were evaluated as MBL inhibitors in double-disk synergy tests (DDSTs), resulting in detection of the first isolate of NDM-1-producing Escherichia coli (NDM-1 Dok01) in Japan. NDM-1 Dok01 was detected when EDTA magnesium disodium salt tetrahydrate (Mg-EDTA), EDTA calcium disodium salt dihydrate, EDTA cobalt disodium salt tetrahydrate and EDTA copper disodium salt tetrahydrate were used as MBL inhibitors. The sensitivity and specificity of DDSTs using Mg-EDTA for 75 MBL producers and 25 non-MBL producers were 96.0% and 100%, respectively. These findings indicate that the DDST method using Mg-EDTA can detect MBL-producing strains, including NDM-1 producers. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

  17. The effect of albumin on the photophysical properties of dimegin photosensitizer

    NASA Astrophysics Data System (ADS)

    Dadeko, A. V.

    2016-12-01

    The effect of albumin on the photophysical properties of a photosensitizer of porphyrin nature, dimegin (disodium salt of 2,4-di(α-methoxyethyl)-deuteroporphyrin-IX), is studied. A slight decrease in the efficiency of generation of singlet oxygen and an increase in the luminescence intensity of the dimegin-albumin complex are shown.

  18. An efficient route for the synthesis of phosphorus-selenium macro-heterocycles.

    PubMed

    Hua, Guoxiong; Slawin, Alexandra M Z; Randall, Rebecca A M; Cordes, David B; Crawford, Luke; Bühl, Michael; Woollins, J Derek

    2013-04-04

    Four-membered ring [PhP(Se)(μ-Se)]2 (Woollins' reagent, WR) reacts with disodium alkenyl-diols followed by in situ ring-closure reaction with appropriate dibromoalkanes affording a series of unusual nine- to fifteen-membered organoselenophosphorus macrocycles bearing the O-P-Se-Cn-Se-P-O or O-P-Se-Cn-O-P-Se linkage.

  19. Effect of short-term feeding duration of diets containing commercial whole-cell yeast or yeast subcomponents on immune function and disease resistance in channel catfish, Ictalurus punctatus

    USDA-ARS?s Scientific Manuscript database

    Juvenile channel catfish (14.4 g average initial weight) were fed diets supplemented with a purified nucleotide mixture for 8 weeks. The mixture consisted of five nucleotides supplied on an equal basis as disodium salts at combined concentrations of 0 (control), 0.1, 0.3, 0.9, or 2.7% of diet. At th...

  20. Effects of dietary supplementation of a purified nucleotide mixture on growth, immune function, and disease and stress resistance in channel catfish, Ictalurus punctatus

    USDA-ARS?s Scientific Manuscript database

    Juvenile channel catfish (14.4 g average initial weight) were fed diets supplemented with a purified nucleotide mixture for 8 weeks. The mixture consisted of five nucleotides supplied on an equal basis as disodium salts at combined concentrations of 0 (control), 0.1, 0.3, 0.9, or 2.7% of diet. At th...

  1. Effects of dietary supplementation of a purified nucleotide mixture on immune function and disease and stress resistance in channel catfish, Ictalurus punctatus

    USDA-ARS?s Scientific Manuscript database

    Juvenile channel catfish (14.4 g average initial weight) were fed diets supplemented with a purified nucleotide mixture for 8 weeks. The mixture consisted of five nucleotides supplied on an equal basis as disodium salts at combined concentrations of 0 (control), 0.1, 0.3, 0.9, or 2.7% of diet. At th...

  2. Case study to examine the effects of a growing-season burn and annosum root disease on mortality in a longleaf pine stand

    Treesearch

    Michelle M. Cram; Dan Shea; Ken Forbus

    2010-01-01

    A case study of a growing-season burn in a longleaf pine (Pinus palustris) stand affected by annosum root disease was conducted at Savannah River Site, SC. The project utilized a longleaf pine stand from a 1995 evaluation of a stump applicator system. The Tim-bor® (disodium octaborate tetrahydrate) and no stump treatment blocks (NST) were...

  3. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... emulsion defoamer. Disodium hydrogen phosphate Do. Formaldehyde Glyceryl monostearate Methyl cellulose... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Acrylate ester copolymer coating. 175.210 Section 175.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  4. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... amount required as a preservative in emulsion defoamer. Disodium hydrogen phosphate Do. Formaldehyde... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Acrylate ester copolymer coating. 175.210 Section 175.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  5. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... emulsion defoamer. Disodium hydrogen phosphate Do. Formaldehyde Glyceryl monostearate Methyl cellulose... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Acrylate ester copolymer coating. 175.210 Section 175.210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

  6. Integrated Protection Against Lyctid Beetle Infestations Part II. - Laboratory Dip-Diffusion Treatment of Unseasoned Banak (Virola spp.) Lumber with Boron Compounds

    Treesearch

    Lonnie H. Williams; Joe K. Mauldin

    1985-01-01

    A manufacturer of conventional moulding wanted a method that would prevent lyctid beetle damage to banak (Virola spp.) wood throughout the period from initial cutting in Brazil until final mouldings were in use. Because complete penetration of wood may be obtained, unseasoned banak wood was treated by dip-diffusion with disodium octaborate...

  7. Graphene-Wrapped Na2C12H6O4 Nanoflowers as High Performance Anodes for Sodium-Ion Batteries.

    PubMed

    Deng, Wenwen; Qian, Jiangfeng; Cao, Yuliang; Ai, Xinping; Yang, Hanxi

    2016-02-03

    Graphene-wrapped organic nanoflowers are synthesized from ultrasonic treatment of a simple microsized disodium salt (Na212H6O4) and graphene, which demonstrates a greatly enhanced electrochemical capacity, rate capability and cycling stability as organic Na(+) storage anode. This work suggests an effective architecture to make organic materials electrochemically energetic and stable for energy storage applications.

  8. 21 CFR 175.210 - Acrylate ester copolymer coating.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., 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 cellulose...

  9. 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 cellulose...

  10. Iminobiotin affinity columns and their application to retrieval of streptavidin.

    PubMed Central

    Hofmann, K; Wood, S W; Brinton, C C; Montibeller, J A; Finn, F M

    1980-01-01

    A method is described for the retrieval of streptavidin from the culture broth of Streptomyces avidinii. The key step in this procedure is the adsorption of streptavidin from culture concentrates to an affinity column in which iminobiotin is attached to AH-Sepharose 4B. This column binds streptavbidin at pH 11 and releases the protein at pH 4. The recovery of streptavidin is practically quantitative. The pH dependence of the iminobiotin-avidin affinity, discovered by Green [Green, N. M. (1966) Biochem. J. 101, 774-779], has thus found practical application. The streptavidin bound 4.07 +/- 0.02 mol of [14C]biotin per mol and was essentially homogeneous as judged by disc and slab gel electrophoresis. Streptavidin was extensively succinoylated without loss of biotin-binding capacity. The observations that 125I-labeled streptavidin and 125I-labeled succinoylstreptavidin are retained by iminobiotin-AH-Sepharose 4B columns at pH 7.5 and are eluted at pH 4.0 provides a convenient purification method for these iodinated proteins. The technique employed for the retrieval of streptavidin is generally applicable to the isolation of iminobiotinylated molecules. PMID:6933515

  11. 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.

  12. Interaction of a trehalose lipid biosurfactant produced by Rhodococcus erythropolis 51T7 with a secretory phospholipase A2.

    PubMed

    Zaragoza, Ana; Teruel, José A; Aranda, Francisco J; Ortiz, Antonio

    2013-10-15

    Trehalose-containing glycolipid biosurfactants form an emerging group of interesting compounds, which alter the structure and properties of phospholipid membranes, and interact with enzymatic and non-enzymatic proteins. Phospholipases A2 constitute a class of enzymes that hydrolyze the sn-2 ester of glycerophospholipids, and are classified into secreted phospholipases A2 (sPLA2) and intracellular phospholipases A2. In this work, pancreatic sPLA2 was chosen as a model enzyme to study the effect of the trehalose lipid biosurfactant on enzymes acting on interfaces. By using this enzyme, it is possible to study the modulation of enzyme activity, either by direct interaction of the biosurfactant with the protein, or as a result of the incorporation of the glycolipid on the phospholipid target membrane. It is shown that the succinoyl trehalose lipid isolated from Rhodococcus erythropolis 51T7 interacts with porcine pancreatic sPLA2 and inhibits its catalytic activity. Two modes of inhibition are observed, which are clearly differentiated by its timescale. First, a slow inhibition of sPLA2 activity upon preincubation of the enzyme with trehalose lipid in the absence of substrate is described. Second, incorporation of trehalose lipid into the phospholipid target membrane gives rise to a fast enzyme inhibition. These results are discussed in the light of previous data on sPLA2 inhibitors and extend the list of interesting biological activities reported for this R. erythropolis trehalose lipid biosurfactant.

  13. Preparation of monoclonal antibody against celangulin V and immunolocalization of receptor in the oriental armyworm, Mythimna separata walker (Lepidoptera: Noctuidae).

    PubMed

    Qi, Zhijun; Xue, Xiaoping; Wu, Wenjun; Zhang, Jiwen; Yang, Runya

    2006-10-04

    The botanical insecticide celangulin V (CA-V) is an insect digestive poison acting on midgut tissue of the target insect larvae. With the aim of localizing the receptor enacted by CA-V, monoclonal antibodies (MAbs) specific to the compound were developed. A hapten was synthesized by introducing a succinoyl into the CA-V structure and conjugated with three carrier proteins. From mice immunized with one conjugate, three MAbs were obtained with a potential capacity of detecting protein-bound residue forms of CA-V in the biological tissues. The oriental armyworm larvae ingested CA-V were examined by the technique of immuno-electron-microscopy (IEM) using the anti-CA-V MAb as the primary antibody and goat anti-mouse/IgG labeled with colloidal gold as the secondary antibody. Electron micrographs of the armyworm midgut tissues showed that the CA-V was associated with the midgut epithelia of the insects. These results demonstrated the existence of a receptor enacted by CA-V on the midgut cells of the oriental armyworm larvae.

  14. 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.

  15. 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.

  16. Evaluation of hypromellose acetate succinate (HPMCAS) as a carrier in solid dispersions.

    PubMed

    Tanno, Fumié; Nishiyama, Yuichi; Kokubo, Hiroyasu; Obara, Sakaé

    2004-01-01

    The utility of hypromellose acetate succinate (HPMCAS), a cellulosic enteric coating agent, as a carrier in a solid dispersion of nifedipine (NP) was evaluated in comparison with other polymers, including hypromellose (HPMC), hypromellose phthalate (HPMCP), methacrylic acid ethyl acrylate copolymer (MAEA), and povidone (PVP). An X-ray diffraction study showed that the minimum amount of HPMCAS required to make the drug completely amorphous was the same as that of other cellulosic polymers, and less than that in dispersions using non-cellulosic polymers. Hypromellose acetate succinate showed the highest drug dissolution level from its solid dispersion in a dissolution study using a buffer of pH 6.8. This characteristic was unchanged after a storage test at high temperature and high humidity. The inhibitory effect of HPMCAS on recrystallization of NP from a supersaturated solution was the greatest among all the polymers examined. Further, the drug release pattern could be modulated by altering the ratio of succinoyl and acetyl moieties in the polymer chain. Our results indicate that HPMCAS is an attractive candidate for use as a carrier in solid dispersions.

  17. Unequivocal glycyrrhizin isomer determination and comparative in vitro bioactivities of root extracts in four Glycyrrhiza species

    PubMed Central

    Farag, Mohamed A.; Porzel, Andrea; Wessjohann, Ludger A.

    2014-01-01

    Glycyrrhiza glabra, commonly known as licorice, is a popular herbal supplement used for the treatment of chronic inflammatory conditions and as sweetener in the food industry. This species contains a myriad of phytochemicals including the major saponin glycoside glycyrrhizin (G) of Glycyrrhetinic acid (GA) aglycone. In this study, 2D-ROESY NMR technique was successfully applied for distinguishing 18α and 18β glycyrrhetinic acid (GA). ROESY spectra acquired from G. glabra, Glycyrrhiza uralensis and Glycyrrhiza inflata crude extracts revealed the presence of G in its β-form. Anti-inflammatory activity of four Glycyrrhiza species, G, glabra, G. uralensis, G. inflata, and G. echinata roots was assessed against COX-1 inhibition revealing that phenolics rather than glycyrrhizin are biologically active in this assay. G. inflata exhibits a strong cytotoxic effect against PC3 and HT29 cells lines, whereas other species are inactive. This study presents an effective NMR method for G isomer assignment in licorice extracts that does not require any preliminary chromatography or any other purification step. PMID:25685548

  18. 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

  19. 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

  20. Hepatic 11 beta-hydroxysteroid dehydrogenase 1 involvement in alterations of glucose metabolism produced by acidotic stress in rat.

    PubMed

    Altuna, M E; Mazzetti, M B; Rago, L F; San Martín de Viale, L C; Damasco, M C

    2009-12-01

    11 beta-hydroxysteroid dehydrogenase (HSDs) enzymes regulate the activity of glucocorticoids in target organs. HSD1, one of the two existing isoforms, locates mainly in CNS, liver and adipose tissue. HSD1 is involved in the pathogenesis of diseases such as obesity, insulin resistance, arterial hypertension and the Metabolic Syndrome. The stress produced by HCl overload triggers metabolic acidosis and increases liver HSD1 activity associated with increased phosphoenolpyruvate carboxykinase, a regulatory enzyme of gluconeogenesis that is activated by glucocorticoids, with increased glycaemia and glycogen breakdown. The aim of this study was to analyze whether the metabolic modifications triggered by HCl stress are due to increased liver HSD1 activity. Glycyrrhetinic acid, a potent HDS inhibitor, was administered subcutaneously (20 mg/ml) to stressed and unstressed four months old maleSprague Dawley rats to investigate changes in liver HSD1, phosphoenolpyruvate carboxykinase (PECPK) and glycogen phosphorylase activities and plasma glucose levels. It was observed that all these parameters increased in stressed animals, but that treatment with glycyrrhetinic acid significantly reduced their levels. In conclusion, our results demonstrate the involvement of HSD1 in stress induced carbohydrate disturbances and could contribute to the impact of HSD1 inhibitors on carbohydrate metabolism and its relevance in the study of Metabolic Syndrome Disorder and non insulin-dependent diabetes mellitus.