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 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  4. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  5. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  6. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  7. 21 CFR 573.360 - Disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  8. 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...

  9. 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...

  10. 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...

  11. 21 CFR 582.6290 - Disodium phosphate.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  12. 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...

  13. 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...

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  19. 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-)....

  20. 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-)....

  1. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

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

    PubMed

    Wang, Weiwei; Xu, Ping; Tang, Hongzhi

    2015-11-17

    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.

  3. 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

  4. 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.

  5. 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.

  6. 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....

  7. 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

  8. 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

  9. 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

  10. 21 CFR 73.2120 - Disodium EDTA-copper.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... practice: Total copper, not less than 13.5 percent. Total (ethylene-dinitrilo) tetracetic acid, not less than 62.5 percent. Free copper, not more than 100 parts per million. Free disodium salt of...

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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...

  16. 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...

  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, 2013 CFR

    2013-07-01

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

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

    Code of Federal Regulations, 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...

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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...

  4. 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...

  5. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  6. 21 CFR 522.161 - Betamethasone acetate and betamethasone disodium phosphate aqueous suspension.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. New Polymorphic Forms of Pemetrexed Diacid and Their Use for the Preparation of Pharmaceutically Pure Amorphous and Hemipentahydrate Forms of Pemetrexed Disodium.

    PubMed

    Michalak, Olga; Łaszcz, Marta; Jatczak, Kamil; Witkowska, Anna; Bujak, Iwona; Groman, Aleksandra; Cybulski, Marcin

    2015-07-30

    The preparation of stable amorphous pemetrexed disodium of pharmaceutical purity as well as the process optimization for the preparation of the hemipentahydrate form of pemetrexed disodium are described. Analytical methods for the polymorphic and chemical purity studies of pemetrexed disodium and pemetrexed diacid forms were developed. The physicochemical properties of the amorphous and hydrate forms of pemetrexed disodium, as well as new forms of pemetrexed diacid (a key synthetic intermediate) were studied by thermal analysis and powder X-ray diffraction. High-performance liquid chromatography and gas chromatography methods were used for the chemical purity and residual solvents determination. In order to study the polymorphic and chemical stability of the amorphous and hemipentahydrate forms, a hygroscopicity test (25 °C, 80% RH) was performed. Powder diffraction and high-performance liquid chromatography analyses revealed that the amorphous character and high chemical purity were preserved after the hygroscopicity test. The hemipentahydrate form transformed completely to the heptahydrate form of pemetrexed disodium. Both pemetrexed disodium forms were produced with high efficiency and pharmaceutical purity in a small commercial scale. Amorphous pemetrexed disodium was selected for further pharmaceutical development. Two new polymorphs (forms 1 and 2) of pemetrexed diacid were used for the preparation of high purity amorphous pemetrexed disodium.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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...

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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).

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. Codelivery of Doxorubicin and shAkt1 by Poly(ethylenimine)-Glycyrrhetinic Acid Nanoparticles To Induce Autophagy-Mediated Liver Cancer Combination Therapy.

    PubMed

    Wang, Feng-Zhen; Xing, Lei; Tang, Zheng-hai; Lu, Jin-Jian; Cui, Peng-Fei; Qiao, Jian-Bing; Jiang, Lei; Jiang, Hu-Lin; Zong, Li

    2016-04-04

    Combination therapy has been developed as a promising therapeutic approach for hepatocellular carcinoma therapy. Here we report a low toxicity and high performance nanoparticle system that was self-assembled from a poly(ethylenimine)-glycyrrhetinic acid (PEI-GA) amphiphilic copolymer as a versatile gene/drug dual delivery nanoplatform. PEI-GA was synthesized by chemical conjugation of hydrophobic GA moieties to the hydrophilic PEI backbone via an acylation reaction. The PEI-GA nanocarrier could encapsulate doxorubicin (DOX) efficiently with loading level about 12% and further condense DNA to form PEI-GA/DOX/DNA complexes to codeliver drug and gene. The diameter of the complexes is 102 ± 19 nm with zeta potential of 19.6 ± 0.2 mV. Furthermore, the complexes possess liver cancer targeting ability and could promote liver cancer HepG2 cell internalization. Apoptosis of cells could be induced by chemotherapy of DOX, and PI3K/Akt/mTOR signaling pathway acts a beneficial effect on the modulation of autophagy. Here, it is revealed that utilizing PEI-GA/DOX/shAkt1 complexes results in effective autophagy and apoptosis, which are useful to cause cell death. The induction of superfluous autophagy is reported to induce type-II cell death and also could increase the sensity of chemotherapy to tumor cells. In this case, combining autophagy and apoptosis is meaningful for oncotherapy. In this study, PEI-GA/DOX/shAkt1 has demonstrated favorable tumor target ability, little side effects, and ideal antitumor efficacy.

  8. 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...

  9. 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...

  10. 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...

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  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. 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).

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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.

  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. 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.

  5. 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.

  6. 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

  7. 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)

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  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. 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

  16. 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.

  17. 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.

  18. 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

  19. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... nonnutritive sweeteners that are listed in § 180.37 of this chapter and that, in addition, are designed for..., does not exceed 0.1 percent by weight of the dry nonnutritive sweetener. (c) To assure the safe use...

  20. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... nonnutritive sweeteners that are listed in § 180.37 of this chapter and that, in addition, are designed for..., does not exceed 0.1 percent by weight of the dry nonnutritive sweetener. (c) To assure the safe use...

  1. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... not exceed 0.1 percent by weight of the dry nonnutritive sweetener. (c) To assure the safe use of the... dressing 75 Do. Sandwich spread 100 Do. Sauces 75 Do. (3) Alone, as a sequestrant in the nonnutritive sweeteners that are listed in § 180.37 of this chapter and that, in addition, are designed for...

  2. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... nonnutritive sweeteners that are listed in § 180.37 of this chapter and that, in addition, are designed for..., does not exceed 0.1 percent by weight of the dry nonnutritive sweetener. (c) To assure the safe use...

  3. 21 CFR 172.135 - Disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Preservative. French dressing 75 Do. Frozen white potatoes including cut potatoes 100 Promote color retention... (parts per million) Use Dressings, nonstandardized 75 Preservative. French dressing 75 Do. Mayonnaise...

  4. 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.

  5. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., nonstandardized 75 Preservative. Dried lima beans (cooked canned) 310 Promote color retention. Egg product that is... cooked canned, other than dried lima beans, pink beans, and red beans) 365 Promote color retention... pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color...

  6. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., nonstandardized 75 Preservative. Dried lima beans (cooked canned) 310 Promote color retention. Egg product that is... cooked canned, other than dried lima beans, pink beans, and red beans) 365 Promote color retention... pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color...

  7. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., nonstandardized 75 Preservative. Dried lima beans (cooked canned) 310 Promote color retention. Egg product that is... cooked canned, other than dried lima beans, pink beans, and red beans) 365 Promote color retention... pie filling 100 Promote color retention. Pink beans (cooked canned) 165 Promote color...

  8. 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)...

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 21 CFR 172.120 - Calcium disodium EDTA.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... malt beverages 25 Antigushing agent. French dressing 75 Preservative. Legumes (all cooked canned, other... Preservative. French dressing 75 Do. Mayonnaise 75 Do. Salad dressing 75 Do. Sandwich spread 100 Do. Sauces...

  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. 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.

  16. 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

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

    ClinicalTrials.gov

    2015-10-14

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

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

    2017-03-23

    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; Stage III Ovarian Cancer; Stage III Pleural Mesothelioma; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIC Ovarian Cancer; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Pleural Mesothelioma; Thymoma; Unresectable Solid Neoplasm

  4. 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

  5. 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.

  6. 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.

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

    ClinicalTrials.gov

    2017-03-06

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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    .... Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate. Magnesium stearate. Magnesium phosphate. Magnesium hydrogen phosphate. Mono-, di-, and trisodium citrate. Mono-, di-, and...

  16. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    .... Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate. Magnesium stearate. Magnesium phosphate. Magnesium hydrogen phosphate. Mono-, di-, and trisodium citrate. Mono-,...

  17. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    .... Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate. Magnesium stearate. Magnesium phosphate. Magnesium hydrogen phosphate. Mono-, di-, and trisodium citrate. Mono-,...

  18. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate. Magnesium stearate. Magnesium phosphate. Magnesium hydrogen phosphate. Mono-, di-, and trisodium citrate. Mono-,...

  19. 21 CFR 181.29 - Stabilizers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    .... Calcium ricinoleate. Calcium stearate. Disodium hydrogen phosphate. Magnesium glycerophosphate. Magnesium stearate. Magnesium phosphate. Magnesium hydrogen phosphate. Mono-, di-, and trisodium citrate. Mono-,...

  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-...

  1. 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...

  2. 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...

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

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  4. 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...

  5. 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...

  6. 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...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

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

    Code of Federal Regulations, 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-...

  9. 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-...

  10. 75 FR 35796 - Busan 74 (2-hydroxypropyl methanethiosulfonate); Chlorine Gas; and Dichromic Acid, et al...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-23

    ... AGENCY Busan 74 (2-hydroxypropyl methanethiosulfonate); Chlorine Gas; and Dichromic Acid, et al... harris.monisha@epa.gov Dichromic Acid EPA-HQ-OPP-2010-02 Rebecca VonDem- Disodium Salt 43 Hagen Dihydrate... Gas; Dichromic Acid, Disodium Salt, Dihydrate, Meta-Cresol (m-Cresol), and Xylenol. Dated: May...

  11. 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

  12. [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.

  13. 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

  14. 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

  15. 78 FR 37230 - Draft and Revised Draft Guidances for Industry Describing Product-Specific Bioequivalence...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ...-specific BE recommendations for drug products containing the following active ingredients: A Apixaban Artemether; Lumefantrine Asenapine maleate B Balsalazide disodium C Cycloserine Cyclosporine E Eltrombopag olamine F Fluoxetine H Hydrochlorothiazide; Triamterene M Medroxyprogesterone (multiple reference...

  16. 21 CFR 139.110 - Macaroni products.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., under the heading “Vacuum Oven Method—Official Final Action,” which is incorporated by reference. Copies... used the label shall bear the statement “Disodium phosphate added for quick cooking”. (2) When...

  17. 21 CFR 139.110 - Macaroni products.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., under the heading “Vacuum Oven Method—Official Final Action,” which is incorporated by reference. Copies... used the label shall bear the statement “Disodium phosphate added for quick cooking”. (2) When...

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. [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.

  3. 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.

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

    PubMed

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

    2013-10-07

    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.

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

    PubMed

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

    1997-03-01

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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  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. 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.

  15. 21 CFR 74.1322 - D&C Red No. 22.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  16. 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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  17. Effects of dietary supplementation of a purified nucleotide mixture on growth, immune function, and disease and stress resistance in channel catfish, Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  18. Effects of dietary supplementation of a purified nucleotide mixture on immune function and disease and stress resistance in channel catfish, Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  19. 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

  20. 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....

  1. 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...

  2. 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. 21 CFR 74.1306 - D&C Red No. 6.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  4. 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...

  5. 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...

  6. 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)...

  7. 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....

  8. 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...

  9. 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...

  10. 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...

  11. 78 FR 14664 - Food and Color Additives; Technical Amendments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-07

    ...-amino-4- - 2-sulfonatophenyl]amino]-9,10-dihydro-9.10-dioxoanthracene-2- sulfonate''; Correct a table...-9,10-dioxoanthracene-2-sulfonate''. Sec. 73.3129 Disodium 1-amino-4- -2- sulfonatophenyl]amino]-9,10-dihydro-9,10-dioxoanthracene-2-sulfonate. * * * * * PART 172--FOOD ADDITIVES PERMITTED FOR DIRECT...

  12. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

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

  13. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  14. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  15. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

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

  16. 21 CFR 74.706 - FD&C Yellow No. 6.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  17. 21 CFR 74.1708 - D&C Yellow No. 8.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1708 D&C Yellow No. 8. (a) Identity. (1) The color additive D&C Yellow No. 8 is principally the disodium salt of fluorescein. (2) Color additive mixtures for use... suitable and that are listed in part 73 of this chapter for use in color additive mixtures for...

  18. 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)

  19. 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.

  20. 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…

  1. 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.

  2. 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.

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

    PubMed Central

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

    2016-01-01

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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

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

    SciTech Connect

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

    1988-01-01

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

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

    SciTech Connect

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

    1988-01-01

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

  13. Redox reactions in micellar systems. communication 4. Eosin-photosensitized reduction of methylviologen

    SciTech Connect

    Nadtochenko, V.; Dzhabiev, T.S.; Rubtsov, I.V.

    1985-12-10

    The authors present data on photosensitized reduction of methylviologen (MV/sup 2 +/) by disodium ethylenediaminetetraacetate (EDTA) in micellar systems modeling, in a first approximation, the structural organization of components of the chain of energy and electron transfer in natural photosynthesis. Photosensitized reduction of methylviologen by EDTA in micellar solutions can model photosystem I of plants with structure formation of reagents and transfer of excitation energy before the step of occurrence of a redox reaction in the active center.

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

    SciTech Connect

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

    1991-05-01

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

  15. Stable Stratification for Solar Ponds

    NASA Technical Reports Server (NTRS)

    Mehta, G. D.

    1982-01-01

    Stable density gradient forms in pond saturated with disodium phosphate (DSP). Volume of DSP saturated water tends to develop temperature and density layers. Since tests indicate thermal and density gradients remain in equilibrium at heat removal rates of 60 percent or more of heat input rate, pond containing DSP would be suitable for collecting solar energy and transferring it to heat exchanger for practical use.

  16. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red 44.... Direct Blue 2 22590 2,7-Naphthalenedisulfonic acid, 5-amino-3- -4-yl]azo]-4-hydroxy-, trisodium salt 2429... 2429-83-6 C.I. Direct Black 4 30245 2,7-Naphthalenedisulfonic acid, 4-amino-3-...

  17. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red 44.... Direct Blue 2 22590 2,7-Naphthalenedisulfonic acid, 5-amino-3- -4-yl]azo]-4-hydroxy-, trisodium salt 2429... 2429-83-6 C.I. Direct Black 4 30245 2,7-Naphthalenedisulfonic acid, 4-amino-3-...

  18. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red 44.... Direct Blue 2 22590 2,7-Naphthalenedisulfonic acid, 5-amino-3- -4-yl]azo]-4-hydroxy-, trisodium salt 2429... 2429-83-6 C.I. Direct Black 4 30245 2,7-Naphthalenedisulfonic acid, 4-amino-3-...

  19. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red 44.... Direct Blue 2 22590 2,7-Naphthalenedisulfonic acid, 5-amino-3- -4-yl]azo]-4-hydroxy-, trisodium salt 2429... 2429-83-6 C.I. Direct Black 4 30245 2,7-Naphthalenedisulfonic acid, 4-amino-3-...

  20. 40 CFR 721.1660 - Benzidine-based chemical substances.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-Naphthalenedisulfonic acid, 4-amino-3- -4-yl]azo]-5-hydroxy-6-(phenylazo)-, disodium salt 2302-97-8 C.I. Direct Red 44.... Direct Blue 2 22590 2,7-Naphthalenedisulfonic acid, 5-amino-3- -4-yl]azo]-4-hydroxy-, trisodium salt 2429... 2429-83-6 C.I. Direct Black 4 30245 2,7-Naphthalenedisulfonic acid, 4-amino-3-...

  1. The AFM method in studies of muscovite mica and galena surfaces

    NASA Astrophysics Data System (ADS)

    Leiro, J. A.; Torhola, M.; Laajalehto, K.

    2017-01-01

    Using atomic force microscopy the freshly cleaved muscovite interfaces in dry air and in water have been studied with atomic resolution. Three different surface layers can be observed for this single crystal. This phenomenon has been ascribed to the weak interactions between the atomic planes. Also, the galena surface has been imaged in dry air and in a disodium tetraborate liquid. In this case the differences have not been so striking. The role of rumpling of surface atoms has been considered.

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

    NASA Astrophysics Data System (ADS)

    Fu, Ruibiao; Hu, Shengmin; Wu, Xintao

    2014-05-01

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

  3. 21 CFR 74.1707a - Ext. D&C Yellow No. 7.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  4. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FD&C Red No. 40. 74.340 Section 74.340 Food and... ADDITIVES SUBJECT TO CERTIFICATION Foods § 74.340 FD&C Red No. 40. (a) Identity. (1) The color additive FD&C Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2)...

  5. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false FD&C Red No. 4. 74.1304 Section 74.1304 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1304 FD&C Red No. 4. (a) Identity. (1) The color additive FD&C Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FD&C Red No. 4. 74.1304 Section 74.1304 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1304 FD&C Red No. 4. (a) Identity. (1) The color additive FD&C Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

  7. 21 CFR 74.1322 - D&C Red No. 22.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false D&C Red No. 22. 74.1322 Section 74.1322 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1322 D&C Red No. 22. (a) Identity. (1) The color additive D&C Red No. 22 is principally the disodium salt of 2′,4′,5′7′-tetrabromofluorescein (CAS Reg. No....

  8. 21 CFR 74.1304 - FD&C Red No. 4.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false FD&C Red No. 4. 74.1304 Section 74.1304 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1304 FD&C Red No. 4. (a) Identity. (1) The color additive FD&C Red No. 4 is principally the disodium salt of 3- -4-hydroxy-1-naphthalenesulfonic acid. (2)...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false D&C Red No. 22. 74.1322 Section 74.1322 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1322 D&C Red No. 22. (a) Identity. (1) The color additive D&C Red No. 22 is principally the disodium salt of 2′,4′,5′7′-tetrabromofluorescein (CAS Reg. No....

  10. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 1 2014-04-01 2014-04-01 false FD&C Red No. 40. 74.340 Section 74.340 Food and... ADDITIVES SUBJECT TO CERTIFICATION Foods § 74.340 FD&C Red No. 40. (a) Identity. (1) The color additive FD&C Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2)...

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

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false D&C Red No. 22. 74.1322 Section 74.1322 Food and... ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1322 D&C Red No. 22. (a) Identity. (1) The color additive D&C Red No. 22 is principally the disodium salt of 2′,4′,5′7′-tetrabromofluorescein (CAS Reg. No....

  12. 21 CFR 74.340 - FD&C Red No. 40.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false FD&C Red No. 40. 74.340 Section 74.340 Food and... ADDITIVES SUBJECT TO CERTIFICATION Foods § 74.340 FD&C Red No. 40. (a) Identity. (1) The color additive FD&C Red No. 40 is principally the disodium salt of 6-hydroxy-5- -2-naphthalenesulfonic acid. (2)...

  13. Implementation of coulometric titration system at constant current for developing of certified materials as primary standards

    NASA Astrophysics Data System (ADS)

    Suarez, H.; Cristancho, R.; Peralta, F.; Torres, H.

    2017-01-01

    Coulometry is a primary method for measuring high purity substances. This is used to certify the primary reference materials required in a chemical analysis process. This paper describes the coulometric titration system developed by the National Metrology Institute (NMI) of Colombia for the certification of hydrochloric acid 0.1mol/kg reference materials. In addition, it also shows preliminary studies for future development of potassium chloride (KCl) and ethylenediaminetetraacetic acid disodium salt (EDTA-Na2) certification.

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

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

  15. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 1 2012-04-01 2012-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

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

    Code of Federal Regulations, 2011 CFR

    2011-04-01

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

  17. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 1 2013-04-01 2013-04-01 false D&C Orange No. 11. 74.1261 Section 74.1261 Food... COLOR ADDITIVES SUBJECT TO CERTIFICATION Drugs § 74.1261 D&C Orange No. 11. (a) Identity. (1) The color additive D&C Orange No. 11 is a mixture consisting principally of the disodium salts of...

  18. 21 CFR 74.1261 - D&C Orange No. 11.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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

  19. 21 CFR 74.1205 - D&C Green No. 5.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 1 2010-04-01 2010-04-01 false D&C Green No. 5. 74.1205 Section 74.1205 Food and... 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...

  20. IR spectroscopic investigation of the inhibition of the glycation process by acetylsalicylic acid

    NASA Astrophysics Data System (ADS)

    Otero de Joshi, Virginia; Gil, Herminia; Contreras, Silvia; Velasquez, William; Joshi, Narahari V.

    2000-05-01

    An IR spectroscopic study was carried out at room temperature for Human Serum albumin (HSA) glycated with fructose and glucose and inhibited with acetylsalicylic acid. The glycation process was carried out in our laboratory by a conventional method to confirm earlier reported observation of the effect of glycation on the intensity variation of the IR spectra, particularly, in the range 1500 cm-1 to 1700 cm-1 and around 3300 cm-1. IR spectra reveal that the effects of glycation of HSA by fructose are more intense than with glucose, which is the expected. Bovine serum albumin was also glycated using Glucose-6-phosphate disodium salt, and gamma-globulin was glycate with glucose, As expected, the glycation process was more intense with glucose-t-phosphate disodium salt. Acetyl salicylic acid was also used and its inhibitor effects could be observed in both cases, with glucose and with glucose-6-phosphate disodium salt even though, to a smaller extent with the latter. This is consistent with the earlier data and is explained on the basis of the attachment of macromolecules to (epsilon) -NH2 groups of lysines. The experimental results confirm that acetylsalicylic acid, indeed, acts as an inhibitor by acetylation of the (epsilon) -NG2 group where the sugars are supposed to be attached.

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

    SciTech Connect

    Not Available

    1980-09-30

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

  2. Phytosteroids beyond estrogens: Regulators of reproductive and endocrine function in natural products.

    PubMed

    Dean, Matthew; Murphy, Brian T; Burdette, Joanna E

    2017-02-15

    Foods and botanical supplements can interfere with the endocrine system through the presence of phytosteroids - chemicals that interact with steroids receptors. Phytoestrogens are well studied, but compounds such as kaempferol, apigenin, genistein, ginsenoside Rf, and glycyrrhetinic acid have been shown to interact with non-estrogen nuclear receptors. These compounds can have agonist, antagonist, or mixed agonist/antagonist activity depending on compound, receptor, cell line or tissue, and concentration. Some phytosteroids have also been shown to inhibit steroid metabolizing enzymes, resulting in biological effects through altered endogenous steroid concentrations. An interesting example, compound A (4-[1-chloro-2-(methylamino)ethyl]phenyl acetate hydrochloride (1:1)) is a promising selective glucocorticoid receptor modulator (SGRM) based on a phytosteroid isolated from Salsola tuberculatiformis Botschantzev. Given that $6.9 billion of herbal supplements are sold each year, is clear that further identification and characterization of phytosteroids is needed to ensure the safe and effective use of botanical supplements.

  3. Glycyrrhizic Acid in the Treatment of Liver Diseases: Literature Review

    PubMed Central

    Li, Jian-yuan; Cao, Hong-yan; Cheng, Gen-hong; Sun, Ming-yu

    2014-01-01

    Glycyrrhizic acid (GA) is a triterpene glycoside found in the roots of licorice plants (Glycyrrhiza glabra). GA is the most important active ingredient in the licorice root, and possesses a wide range of pharmacological and biological activities. GA coupled with glycyrrhetinic acid and 18-beta-glycyrrhetic acid was developed in China or Japan as an anti-inflammatory, antiviral, and antiallergic drug for liver disease. This review summarizes the current biological activities of GA and its medical applications in liver diseases. The pharmacological actions of GA include inhibition of hepatic apoptosis and necrosis; anti-inflammatory and immune regulatory actions; antiviral effects; and antitumor effects. This paper will be a useful reference for physicians and biologists researching GA and will open the door to novel agents in drug discovery and development from Chinese herbs. With additional research, GA may be more widely used in the treatment of liver diseases or other conditions. PMID:24963489

  4. (+)-Methyl 3β-acet­oxy-13-carb­oxy-19-hy­droxy-11-oxo-C-norolean-18-en-30-oate γ-lactone

    PubMed Central

    Gaware, Rawindra; Czollner, Laszlo; Jordis, Ulrich; Mereiter, Kurt

    2010-01-01

    The title compound, C33H46O7, is an unusual oxydation product of the therapeutic agent glycyrrhetinic acid that has, in comparison to the latter, a distinctly altered triterpene structure with one five- and four six-membered carbocycles complemented by a γ-lactone ring with a spiro-junction and a ring double bond. The junction between the five-membered ring C, a cyclo­penta­none ring, and the six-membered ring D, previously in question, was found to be cis, confirming earlier structure assignments based solely on chemical transformations. In the solid state, the compound exhibits five intra- and four inter­molecular C—H⋯O inter­actions with H⋯O distances less than or equal to 2.70 Å and C—H⋯O greater than 100°. PMID:21587575

  5. Plant Natural Compounds with Antibacterial Activity towards Common Pathogens of Pond-Cultured Channel Catfish (Ictalurus punctatus)

    PubMed Central

    Schrader, Kevin K.

    2010-01-01

    The bacteria Edwardsiella ictaluri and Flavobacterium columnare cause enteric septicemia and columnaris disease, respectively, in channel catfish (Ictalurus punctatus). Natural therapeutants may provide an alternative to current management approaches used by producers. In this study, a rapid bioassay identified plant compounds as potential therapeutants. Chelerythrine chloride and ellagic acid were the most toxic toward E. ictaluri, with 24-h IC50 of 7.3 mg/L and 15.1 mg/L, respectively, and MIC of 2.1 mg/L and 6.5 mg/L, respectively. Chelerythrine chloride, ellagic acid, β-glycyrrhetinic acid, sorgoleone, and wogonin were the most toxic towards two genomovars of F. columnare, and wogonin had the strongest antibacterial activity (MIC = 0.3 mg/L). PMID:22069655

  6. Functional role of gap junctions in cytokine-induced leukocyte adhesion to endothelium in vivo

    PubMed Central

    Véliz, Loreto P.; González, Francisco G.; Duling, Brian R.; Sáez, Juan C.; Boric, Mauricio P.

    2008-01-01

    To assess the hypothesis that gap junctions (GJs) participate on leukocyte-endothelium interactions in the inflammatory response, we compared leukocyte adhesion and transmigration elicited by cytokine stimulation in the presence or absence of GJ blockers in the hamster cheek pouch and also in the cremaster muscle of wild-type (WT) and endothelium-specific connexin 43 (Cx43) null mice (Cx43e−/−). In the cheek pouch, topical tumor necrosis factor-α (TNF-α; 150 ng/ml, 15 min) caused a sustained increment in the number of leukocytes adhered to venular endothelium (LAV) and located at perivenular regions (LPV). Superfusion with the GJ blockers 18-α-glycyrrhetinic acid (AGA; 75 μM) or 18-β-glycyrrhetinic acid (50 μM) abolished the TNF-α-induced increase in LAV and LPV; carbenoxolone (75 μM) or oleamide (100 μM) reduced LAV by 50 and 75%, respectively, and LPV to a lesser extent. None of these GJ blockers modified venular diameter, blood flow, or leukocyte rolling. In contrast, glycyrrhizin (75 μM), a non-GJ blocker analog of AGA, was devoid of effect. Interestingly, when AGA was removed 90 min after TNF-α stimulation, LAV started to rise at a similar rate as in control. Conversely, application of AGA 90 min after TNF-α reduced the number of previously adhered cells. In WT mice, intrascrotal injection of TNF-α (0.5 μg/0.3 ml) increased LAV (fourfold) and LPV (threefold) compared with saline-injected controls. In contrast to the observations in WT animals, TNF-α stimulation did not increase LAV or LPV in Cx43e−/− mice. These results demonstrate an important role for GJ communication in leukocyte adhesion and transmigration during acute inflammation in vivo and further suggest that endothelial Cx43 is key in these processes. PMID:18599597

  7. Enzymatic biotransformation of terpenes as bioactive agents.

    PubMed

    Sultana, Nighat; Saify, Zafar Saeed

    2013-12-01

    The plant-derived terpenoids are considered to be the most potent anticancer, anti-inflammatory and anticarcinogenic compounds known. Enzymatic biotransformation is a very useful approach to expand the chemical diversity of natural products. Recent enzymatic biotransformation studies on terpenoids have resulted in the isolation of novel compounds. 14-hydroxy methyl caryophyllene oxide produced from caryophyllene oxide showed a potent inhibitory activity against the butyryl cholinesterase enzyme, and was found to be more potent than parent caryophyllene oxide. The metabolites 3β,7β-dihydroxy-11-oxo-olean-12-en-30-oic acid, betulin, betulonic acid, argentatin A, incanilin, 18β glycyrrhetinic acid, 3,11-dioxo-olean-12-en-30-oic acid produced from 18β glycyrrhetinic acid were screened against the enzyme lipoxygenase. 3,11-Dioxo-olean-12-en-30-oic acid, was found to be more active than the parent compound. The metabolites 3β-hydroxy sclareol 18α-hydroxy sclareol, 6α,18α-dihydroxy sclareol, 11S,18α-dihydroxy sclareol, and 1β-hydroxy sclareol and 11S,18α-dihydroxy sclareol produced from sclareol were screened for antibacterial activity. 1β-Hydroxy sclareol was found to be more active than parent sclareol. There are several reports on natural product enzymatic biotransformation, but few have been conducted on terpenes. This review summarizes the classification, advantages and agents of enzymatic transformation and examines the potential role of new enzymatically transformed terpenoids and their derivatives in the chemoprevention and treatment of other diseases.

  8. Screening of gap junction antagonists on dye coupling in the rabbit retina

    PubMed Central

    PAN, FENG; MILLS, STEPHEN L.; MASSEY, STEPHEN C.

    2008-01-01

    Many cell types in the retina are coupled via gap junctions and so there is a pressing need for a potent and reversible gap junction antagonist. We screened a series of potential gap junction antagonists by evaluating their effects on dye coupling in the network of A-type horizontal cells. We evaluated the following compounds: meclofenamic acid (MFA), mefloquine, 2-aminoethyldiphenyl borate (2-APB), 18-α-glycyrrhetinic acid, 18-β-glycyrrhetinic acid (18-β-GA), retinoic acid, flufenamic acid, niflumic acid, and carbenoxolone. The efficacy of each drug was determined by measuring the diffusion coefficient for Neurobiotin (Mills & Massey, 1998). MFA, 18-β-GA, 2-APB and mefloquine were the most effective antagonists, completely eliminating A-type horizontal cell coupling at a concentration of 200 μM. Niflumic acid, flufenamic acid, and carbenoxolone were less potent. Additionally, carbenoxolone was difficult to wash out and also may be harmful, as the retina became opaque and swollen. MFA, 18-β-GA, 2-APB and mefloquine also blocked coupling in B-type horizontal cells and AII amacrine cells. Because these cell types express different connexins, this suggests that the antagonists were relatively non-selective across several different types of gap junction. It should be emphasized that MFA was water-soluble and its effects on dye coupling were easily reversible. In contrast, the other gap junction antagonists, except carbenoxolone, required DMSO to make stock solutions and were difficult to wash out of the preparation at the doses required to block coupling in A-type HCs. The combination of potency, water solubility and reversibility suggest that MFA may be a useful compound to manipulate gap junction coupling. PMID:17711600

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

    NASA Astrophysics Data System (ADS)

    Varghese, Nisha

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

  10. Stability assessment of hypromellose acetate succinate (HPMCAS) NF for application in hot melt extrusion (HME).

    PubMed

    Sarode, Ashish L; Obara, Sakae; Tanno, Fumie K; Sandhu, Harpreet; Iyer, Raman; Shah, Navnit

    2014-01-30

    HPMCAS is a widely used polymer in the pharmaceutical industry as an excipient. In this work, the physicochemical stability of HPMCAS was investigated for hot melt extrusion (HME) application. The reduction in zero rate viscosity (η0) of the polymer with the increase in temperature was determined using rheological evaluation prior to HME processing. The energy of activation for AS-MF determined by fitting Arrhenius model to the temperature dependent reduction in η0 was found to be slightly lower than that for the other grades of HPMCAS. Glassy yellowish HMEs were obtained using Haake Mini-Lab MicroCompounder operated at 160, 180, and 200°C and 100, 200, and 300 rpm for all the grades at each temperature. Various physicochemical properties of HPMCAS such as glass transition temperature, semi-crystalline nature, solid state functional group properties, moisture content, and solution viscosity were not significantly affected by the HME processing. The most significant change was the release of acetic and succinic acid with the increase in HME temperature and speed. The free acid content release due to HME was directly proportional to the speed at lower operating temperatures. AS-LF was found to be the most stable with the lowest increase in total free acid content even at higher HME temperature and speed. Although the dissolution time was not affected due to HME for AS-LF and AS-MF grades, it was notably increased for AS-HF, perhaps due to significant reduction of succinoyl content. In conclusion, the HME processing conditions for solid dispersions of HPMCAS should be based on the acceptance levels of free acid for the drug and the drug product.

  11. Dextrin-colistin conjugates as a model bioresponsive treatment for multidrug resistant bacterial infections.

    PubMed

    Ferguson, Elaine L; Azzopardi, Ernest; Roberts, Jessica L; Walsh, Timothy R; Thomas, David W

    2014-12-01

    Polymer therapeutics offer potential benefits in the treatment of multidrug resistant (MDR) infections; affording targeted delivery of biologically active agents to the site of inflammation, potential decreases in systemic toxicity, and the retention of antimicrobial activity at the target site. As a prototype model, these studies developed and characterized a library of dextrin-colistin conjugates (dextrin molecular weight: 7500-48,000 g/mol) as a means of targeting the delivery of colistin. Optimum colistin release kinetics (following dextrin degradation by physiological concentrations of amylase (100 IU/L)) were observed in conjugates containing low molecular weight (∼7500 g/mol) dextrin with ∼1 mol % succinoylation (∼80% drug release within 48 h, compared to ∼33% from sodium colistin methanesulfonate (CMS, Colomycin)). These conjugates exhibited comparable antimicrobial activity to CMS in conventional MIC assays against a range of Gram-negative pathogens, but with significantly reduced in vitro toxicity toward kidney (IC₅₀ = CMS, 15.4 μg/mL; dextrin-colistin, 63.9 μg/mL) and macrophage (IC₅₀ = CMS, 111.3 μg/mL; dextrin-colistin, 303.9 μg/mL) cells. In vivo dose-escalation studies in rats demonstrated improved pharmacokinetics of the conjugates, with prolonged plasma levels of colistin (t₁/₂ 135-1271 min vs 53 min) and decreased toxicity, compared to colistin sulfate. These studies highlight the potential utility of "nanoantibiotic" polymer therapeutics to aid the safe, effective, and targeted delivery of colistin in the management of MDR infections.

  12. Crystal structure of Na2HfSi2O7 by Rietveld refinement.

    PubMed

    Massoni, Nicolas; Chevreux, Pierrick

    2016-10-01

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

  13. Pharmacology of Nasal Medications: An Update

    PubMed Central

    Martin, G. F.

    1988-01-01

    The author of this article reviews the pharmacology of nasal medication, focusing on the indications and side-effects. The newer group of non-sedating antihistamines proves to be a useful supplement to disodium cromoglycate and the traditional antihistamines in the treatment of allergic rhinitis. The topical steroids (flunisolide and beclomethasone dipropionate) did not produce a significant incidence of adrenal suppression, mucosal atrophy, or nasal candidiasis. The anticholinergic ipatropium bromide shows promise in the treatment of rhinorrhea. The author also reviews the use of decongestants and emollients and remarks on the factors that affect patient compliance when nasal medications are prescribed. PMID:20469495

  14. Crystal structure of Na2HfSi2O7 by Rietveld refinement

    PubMed Central

    Massoni, Nicolas; Chevreux, Pierrick

    2016-01-01

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

  15. Pseudothrombocytopenia with multiple anticoagulant sample collection tubes

    PubMed Central

    Kovacs, Ferenc; Varga, Marina; Pataki, Zsolt; Rigo, Erzsebet

    2016-01-01

    The knowledge of pseudothrombocytopenia (PTCP) is important for the accuracy of a clinical assessment and for avoiding unnecessary treatment. An elderly patient was hospitalized with left lung pneumonia. Severe thrombocytopenia [platelet (PLT) number: 18 × 109/L] without any clinical bleeding was found in ethylenediaminetetraacetic acid blood collection tube. PLT measurement was repeated in various anticoagulant [sodium citrate, lithium heparin, disodium oxalate, hirudin, and magnesium sulfate (Mg-sulfate)] sample collection tubes and all of them showed thrombocytopenia except with Mg-sulfate. To the best of our knowledge, PTCP with five anticoagulant sample collection tubes has not been reported earlier. PMID:28180009

  16. Sterile Culture of Rotylenchulus reniformis on Tomato Root with Gellan Gum as a Supporting Medium

    PubMed Central

    Eyre, Melissa J.; Caswell, Edward P.

    1991-01-01

    Rotylenchulus reniformis was repeatedly propagated in sterile excised tomato roots growing on modified White's medium with gellan gum as the support. Gellan gum provided an optically clear support medium that could be liquified by adding 5 mM disodium ethylenediaminetetraacetate (EDTA) to facilitate nematode extraction. Liquefaction of the gellan-gum medium by EDTA allowed efficient recovery of eggs and vermiform stages of R. reniformis. Extraction efficiency was quantified with Radopholus similis as a test organism. The efficiency of extracting R. similis from the gellan gum did not vary with the concentrations of EDTA tested. PMID:19283117

  17. Sterile Culture of Rotylenchulus reniformis on Tomato Root with Gellan Gum as a Supporting Medium.

    PubMed

    Eyre, M J; Caswell, E P

    1991-04-01

    Rotylenchulus reniformis was repeatedly propagated in sterile excised tomato roots growing on modified White's medium with gellan gum as the support. Gellan gum provided an optically clear support medium that could be liquified by adding 5 mM disodium ethylenediaminetetraacetate (EDTA) to facilitate nematode extraction. Liquefaction of the gellan-gum medium by EDTA allowed efficient recovery of eggs and vermiform stages of R. reniformis. Extraction efficiency was quantified with Radopholus similis as a test organism. The efficiency of extracting R. similis from the gellan gum did not vary with the concentrations of EDTA tested.

  18. Simplified qualitative method for canavanine in seeds and sprouts.

    PubMed

    Rajkowski, Kathleen T

    2004-01-01

    The major stored nitrogen compound in alfalfa seeds is canavanine. To identify this nonprotein amino acid from seed extract and sprout water, a qualitative micro-thin-layer chromatography method was developed. Successful separation and identification was achieved using microsilica plates, a 70:30 ethyl alcohol-water solvent system, and 1% ammonium disodium pentacyanoammineferrate II for color development. This quick method was used to identify canavanine (sensitivity 50 microg) from irradiated and nonirradiated alfalfa and clover seed extracts and alfalfa sprout water. Broccoli and radish seed extracts were negative for canavanine. This simple method is useful to track the release and decrease of canavanine in the sprout water.

  19. TRACER STABILITY AND CHEMICAL CHANGES IN AN INJECTED GEOTHERMAL FLUID DURING INJECTION-BACKFLOW TESTING AT THE EAST MESA GEOTHERMAL FIELD

    SciTech Connect

    Adams, M.C.

    1985-01-22

    The stabilities of several tracers were tested under geothermal conditions while injection-backflow tests were conducted at East Mesa. The tracers I and Br were injected continuously while SCN (thiocyanate), B, and disodium fluorescein were each injected as a point source (slug). The tracers were shown to be stable, except where the high concentrations used during slug injection induced adsorption of the slug tracers. However, adsorption of the slug tracers appeared to ''armor'' the formation against adsorption during subsequent tests. Precipitation behavior of calcite and silica as well as Na/K shifts during injection are also discussed.

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

    SciTech Connect

    Fu, Ruibiao Hu, Shengmin; Wu, Xintao

    2014-05-01

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

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

    SciTech Connect

    Not Available

    1988-05-01

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

  2. Ethylenediaminetetraacetic acid (EDTA) as an auxiliary tool in the electrospray ionization mass spectrometry analysis of native and derivatized beta-cyclodextrins, maltoses, and fructans contaminated with Ca and/or Mg.

    PubMed

    Giudicessi, Silvana L; Fatema, M Kaniz; Nonami, Hiroshi; Erra-Balsells, Rosa

    2010-09-01

    The effect of Ca(2+) (and Mg(2+)) and the disodium salt of ethylenediaminetetraacetic acid (EDTA), a well known Ca(2+) (and Mg(2+)) chelating agent, on the volatilization/ionization of carbohydrates by using electrospray ionization mass spectrometry has been studied. Model compounds such as maltoses (maltose to maltoheptaose), beta-cyclodextrins (beta-cyclodextrin, methyl-beta-cyclodextrin, heptakis(2,6-di-O-methyl)-beta-cyclodextrin, heptakis(2,3,6-tri-O-methyl)-beta-cyclodextrin, and 2-hydroxypropyl-beta-cyclodextrin) and fructans (sucrose, 1-ketose, nystose, and 1F-fructofuranosylnystose) were used.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2013-01-01

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

  5. Polyimides prepared from perfluoroisopropylidene diamine

    NASA Technical Reports Server (NTRS)

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

    1978-01-01

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

  6. Remote Environmental Monitoring and Diagnostics in the Perishables Supply Chain - Phase 2

    DTIC Science & Technology

    2014-03-20

    enzyme, natural flavors, sodium citrate, sodium carbonate, disodium phosphate,  annatto as a color agent], partially hydrogenated  soybean  and cottonseed...food starch,  maltodextrin, natural and artificial flavors, partially hydrogenated  soybean  oil, water, soy  lecithin], glucono‐delta‐lactone, calcium...flour (bleached flour, malted barley  flour, niacin, reduced iron, thiamine mononitrate, riboflavin, folic acid), water, partially  hydrogenated  soybean

  7. Total Synthesis of Eleutherobin and Analogs and Study of Anti-Cancer Mechanism

    DTIC Science & Technology

    2001-05-01

    RX NO 7080] 07/27/2001 FRI 15:19 FAX 732 595 9556 MERCK & CO-BLDG 800-B113 l[009 LUý salt bridge: ,rC7staMCbeft1StJy$3)e as jf7-.) CP 3& 4 syr...installation of the remaining T. T. Dabrah for their encouragement by providing valuable fermen - functionallty required to go from 3 to the CP compounds...the natural anhydnide :has been opened to form a disodium salt ) a strong series (7R) by base-catalyzed equilibration starting with the prcfcrcnc.f~or

  8. Synthesis and crystal structure of a new alluaudite-like iron phosphate Na2CaMnFe(PO4)3

    PubMed Central

    Jebli, Semeh; Badri, Abdessalem; Ben Amara, Mongi

    2016-01-01

    A new iron phosphate, disodium calcium manganese(II) iron(III) tris(phosphate), Na2CaMnFe(PO4)3, has been synthesized as single crystals by the flux technique. This compound crystallizes in the monoclinic space group C2/c. The structure belongs to the alluaudite structural type and thus, it obeys the X(2)X(1)M(1)M(2)2(PO4)3 general formula. Both the X(2) and X(1) sites are fully occupied by sodium, while M(1) is occupied by calcium and M(2) exhibits a statistical distribution of iron and manganese. PMID:27980835

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

    USGS Publications Warehouse

    Shapiro, L.; Brannock, W.W.

    1955-01-01

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

  10. Insights into the mechanism of Pseudomonas dacunhae aspartate beta-decarboxylase from rapid-scanning stopped-flow kinetics.

    PubMed

    Phillips, Robert S; Lima, Santiago; Khristoforov, Roman; Sudararaju, Bakthavatsalam

    2010-06-22

    The mechanism of wild-type and R37A mutant Pseudomonas dacunhae aspartate beta-decarboxylase (ABDC) was studied by rapid-scanning stopped-flow spectrophotometry. Mixing wild-type ABDC with 50 mM disodium l-Asp resulted in the formation of a 325 nm absorption peak within the dead time of the stopped-flow instrument, likely the ketimine of pyridoxamine 5'-phosphate and oxaloacetate or pyruvate. After consumption of the l-Asp, the 360 nm feature of the resting enzyme was restored. Thus, the 325 nm species is a catalytically competent intermediate. In contrast, mixing wild-type ABDC with the disodium salt of either threo- or erythro-beta-hydroxy-dl-Asp at 50 mM resulted in a much slower formation of the 325 nm complex, with an apparent rate constant of approximately 1 or 0.006 s(-1), respectively. When wild-type ABDC is mixed with disodium succinate, a nonreactive analogue of l-Asp, formation of a new peak at 425 nm is observed. The apparent rate constant for formation of the 425 nm band exhibits a hyperbolic dependence on succinate concentration, showing that there is a rapid binding equilibrium, followed by a slower reaction in which the internal aldimine is protonated on the Schiff base N. Hydrostatic pressure shifts the spectrum from the 425 nm form to the 360 nm form, consistent with a conformational change. It is likely that the binding of substrate or analogues induces a conformational change that releases strain in the Lys pyridoxal 5'-phosphate Schiff base and increases the pK(a), resulting in protonation of the Schiff base to initiate transaldimination. Mixing of R37A mutant ABDC with 50 mM l-Asp also results in the formation of the 325 nm complex, but with an apparent rate constant of 0.2 s(-1), at least 5000-fold slower than the rate of wild-type ABDC. In contrast to wild-type ABDC, R37A ABDC shows no change in the cofactor spectrum when mixed with disodium succinate. These results suggest that Arg-37, a conserved active site residue in ABDC, plays a role

  11. Theoretical Prediction of the Heats of Formation, Densities and Relative Sensitivities, and/or Synthetic Approaches Toward the Synthesis of High Energy Dense Materials (HEDMs): 3,5-Dinitro-1,3,5-Oxadiazinane, Bis-Adjacent RDX, Bis-Adjacent HMX, 4,4’,6,6’-Tetranitro-1,1’-Bis(N-oxide)-5,5’,6,6’-4H,4’H-5,5’-Bisimidazo Oxadiazole, and the Open-Cage Derivative of CL-20

    DTIC Science & Technology

    2015-09-01

    hydrogenolysis, followed by nitration . Ring opening of the dinitrourea cyclic ether with NaOH, followed by reacidification of the disodium dinitramine...oC, 2 h O 8 (95%) 1. H2, Pd/C, Ac2O 2. Nitration 3.. NaOH, H2O; then reacidify NH O HN 9 O2N NO2 Polymerize for energetic binders Metal salts for...nitrolysis occurs a ethylene fusion Dodecagen (13) Nitration Conditions With tetracycle 12 in hand, the stage is now set for nitration of this

  12. Fluorinated aromatic diamine

    NASA Technical Reports Server (NTRS)

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

    1980-01-01

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

  13. An improved simple colorimetric method for quantitation of non-transferrin-bound iron in serum.

    PubMed

    Zhang, D; Okada, S; Kawabata, T; Yasuda, T

    1995-03-01

    A simple method for direct quantitation of non-transferrin-bound iron (NTBI) in serum is introduced. NTBI was separated from serum by adding excess nitrilotriacetic acid disodium salt (NTA) to serum to form an Fe-NTA complex and then ultrafiltrated using a micro-filter. The NTBI in the ultrafiltrate was quantitated using a bathophenanthroline-based method. The optimal detection condition and several potential confounding factors were investigated. The actual measurements to samples in vivo and in vitro showed that this method is very practical.

  14. TRPV4 in porcine lens epithelium regulates hemichannel-mediated ATP release and Na-K-ATPase activity.

    PubMed

    Shahidullah, Mohammad; Mandal, Amritlal; Delamere, Nicholas A

    2012-06-15

    In several tissues, transient receptor potential vanilloid 4 (TRPV4) channels are involved in the response to hyposmotic challenge. Here we report TRPV4 protein in porcine lens epithelium and show that TRPV4 activation is an important step in the response of the lens to hyposmotic stress. Hyposmotic solution (200 mosM) elicited ATP release from intact lenses and TRPV4 antagonists HC 067047 and RN 1734 prevented the release. In isosmotic solution, the TRPV4 agonist GSK1016790A (GSK) elicited ATP release. When propidium iodide (PI) (MW 668) was present in the bathing medium, GSK and hyposmotic solution both increased PI entry into the epithelium of intact lenses. Increased PI uptake and ATP release in response to GSK and hyposmotic solution were abolished by a mixture of agents that block connexin and pannexin hemichannels, 18α-glycyrrhetinic acid and probenecid. Increased Na-K-ATPase activity occurred in the epithelium of lenses exposed to GSK and 18α-glycyrrhetinic acid + probenecid prevented the response. Hyposmotic solution caused activation of Src family kinase and increased Na-K-ATPase activity in the lens epithelium and TRPV4 antagonists prevented the response. Ionomycin, which is known to increase cytoplasmic calcium, elicited ATP release, the magnitude of which was no greater when lenses were exposed simultaneously to ionomycin and hyposmotic solution. Ionomycin-induced ATP release was significantly reduced in calcium-free medium. TRPV4-mediated calcium entry was examined in Fura-2-loaded cultured lens epithelium. Hyposmotic solution and GSK both increased cytoplasmic calcium that was prevented by TRPV4 antagonists. The cytoplasmic calcium rise in response to hyposmotic solution or GSK was abolished when calcium was removed from the bathing solution. The findings are consistent with hyposmotic shock-induced TRPV4 channel activation which triggers hemichannel-mediated ATP release. The results point to TRPV4-mediated calcium entry that causes a cytoplasmic

  15. The influence of P/As substitution in the melilite-like Na2Co(P2-xAsx)O7 (x = 0.40 and 0.93) solid solutions.

    PubMed

    Issaoui, Chokri; Chebbi, Hammouda; Guesmi, Abderrahmen

    2017-04-01

    To investigate the influence of P/As substitution on structures and electrical properties, e.g. the effect on material densities, two new solid P/As-doped solutions, Na2CoP1.60As0.40O7 (disodium cobalt diphosphorus arsenic heptaoxide) and Na2CoP1.07As0.93O7 (disodium cobalt phosphorus arsenic heptaoxide), with melilite-like structures have been synthesized by solid-state reactions. Their unit-cell parameters are in agreement with Vegard's law. The obtained structural models were investigated by the bond valence sum (BVS) and charge distribution (CHARDI) validation tools and, for the latter, the structures are described as being built on anion-centred polyhedra. The frameworks can be described as layered and formed by {[Co(P,As)2O7](2-)}∞ slabs, with alkali cations sandwiched between the layers and with the interlayer spaces increased due to P/As substitution. The BVS model was extended to a preliminary simulation of the sodium conduction properties in the studied structural type and suggests that the most probable sodium conduction pathways are bidimensional, at the (002) planes.

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

    PubMed

    Dolowy, Małgorzata; Pyka, Alina

    2014-01-01

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

  17. Orodispersible films in individualized pharmacotherapy: The development of a formulation for pharmacy preparations.

    PubMed

    Visser, J Carolina; Woerdenbag, Herman J; Crediet, Stefan; Gerrits, Edwin; Lesschen, Marjan A; Hinrichs, Wouter L J; Breitkreutz, Jörg; Frijlink, Henderik W

    2015-01-15

    Orodispersible films (ODFs) are promising drug delivery systems for customized small scale pharmacy preparations. The aim of the present study was to develop a versatile casting solution suitable for the extemporaneous production of ODFs to which active pharmaceutical ingredients (APIs) can be added. Different combinations of film forming agents and other excipients and different casting heights were tested for their suitability for production of ODFs. The best suitable casting solution contained hypromellose, carbomer, glycerol, disodium EDTA and trometamol. This casting solution was used to prepare ODFs containing water-soluble APIs (enalapril maleate and prednisolone disodium phosphate) and a poorly water-soluble API (diazepam) for which ethanol 96% was used as co-solvent.The water-soluble APIs as well as ethanol influenced the viscosity of the casting solution, mechanical properties and disintegration time of the ODFs. All ODFs containing API met the requirements on uniformity of mass and uniformity of content set by the European Pharmacopoeia (2014) (Ph. Eur.) 8th edition. In conclusion, ODFs of good pharmaceutical quality can be prepared on small scale. Hereby opening the perspective of using ODFs for individualized pharmacotherapy.

  18. Improved FK506 production by the precursors and product-tolerant mutant of Streptomyces tsukubaensis based on genome shuffling and dynamic fed-batch strategies.

    PubMed

    Du, Wenjie; Huang, Di; Xia, Menglei; Wen, Jianping; Huang, Ming

    2014-07-01

    FK506, a secondary metabolite produced by Streptomyces tsukubaensis, is well known for its immunosuppressant properties to prevent rejection of transplanted organs and treat autoimmune diseases. However, the low titer of FK506 in the original producer strain limits the further industrialization efforts and restricts its clinical applications. To address this issue, a highly efficient method combined genome shuffling and dynamic fed-batch strategies was systematically performed in this work. Firstly, after five rounds of genome shuffling based on precursors and product resistances, a higher yielding strain TJ-P325 was successfully acquired, whose production reached 365.6 mg/L, 11-fold increase compared with the original strain. Then, the possible mechanism of different production capabilities between TJ-P325 and the wild type was explored through comparative gene expression analysis of key genes. Results showed that the transcription level of key genes was altered significantly in the mutant. Moreover, precursors addition enhanced the FK506 production by 28 %, as well as reduced the by-products biosynthesis. Finally, the disodium malonate and disodium methylmalonate dynamic fed-batch strategies dramatically led to the production of 514.5 mg/L in a 7.5-L bioreactor. These results demonstrated that genome shuffling and dynamic fed-batch strategies could be successfully applied to generate high-yield strains with value-added natural products during industrial microbial fermentation.

  19. Purification of fallout-contaminated water studied

    SciTech Connect

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

    1983-04-30

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

  20. Surfactants, Aromatic and Isoprenoid Compounds, and Fatty Acid Biosynthesis Inhibitors Suppress Staphylococcus aureus Production of Toxic Shock Syndrome Toxin 1▿

    PubMed Central

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

    2009-01-01

    Menstrual toxic shock syndrome is a rare but potentially life-threatening illness manifest through the actions of Staphylococcus aureus toxic shock syndrome toxin 1 (TSST-1). Previous studies have shown that tampon additives can influence staphylococcal TSST-1 production. We report here on the TSST-1-suppressing activity of 34 compounds that are commonly used additives in the pharmaceutical, food, and perfume industries. Many of the tested chemicals had a minimal impact on the growth of S. aureus and yet were potent inhibitors of TSST-1 production. The TSST-1-reducing compounds included surfactants with an ether, amide, or amine linkage to their fatty acid moiety (e.g., myreth-3-myristate, Laureth-3, disodium lauroamphodiacetate, disodium lauramido monoethanolamido, sodium lauriminodipropionic acid, and triethanolamine laureth sulfate); aromatic compounds (e.g. phenylethyl and benzyl alcohols); and several isoprenoids and related compounds (e.g., terpineol and menthol). The membrane-targeting and -altering effects of the TSST-1-suppressing compounds led us to assess the activity of molecules that are known to inhibit fatty acid biosynthesis (e.g., cerulenin, triclosan, and hexachlorophene). These compounds also reduced S. aureus TSST-1 production. This study suggests that more additives than previously recognized inhibit the production of TSST-1. PMID:19223628

  1. Anionic Gemini Surfactants:. Synthesis and Surface Active Properties

    NASA Astrophysics Data System (ADS)

    Shukla, Dipti; Tyagi, V. K.

    New compounds bearing two phosphate groups and two long chain (dodecyl) were prepared by two-step reaction: (i) phosphorylation of dodecanol with pyrophosphoric acid, (ii) reaction of dodecyl phosphate with N(CH3)4OH and 1,6-dibromo hexane. The effect of reaction variables like time and molar ratio of reactants on yield has also been reported. The 1:2:0.5 molar ratio of reactants (dodecyl phosphate, N(CH3)4OH, and Br(CH2)6 Br, respectively) and 3 h duration resulted to give maximum yield of anionic gemini surfactants. The structure of synthesized surfactant was investigated by modern analytical techniques, viz. FT-IR, 1H NMR, 13C NMR. Amphipathic disodium phosphates were obtained by neutralization of free acids with sodium hydroxide and their surface active properties in aqueous solution were measured. These disodium phosphates possessed 77.3% anionic content and showed good water solubility. Foaming properties and wetting ability were also evaluated.

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

    PubMed

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

    2013-06-01

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

  3. Characterisation of the anodic layers formed on 2024 aluminium alloy, in tetraborate electrolyte containing molybdate ions

    NASA Astrophysics Data System (ADS)

    Moutarlier, V.; Pelletier, S.; Lallemand, F.; Gigandet, M. P.; Mekhalif, Z.

    2005-12-01

    Anodic layer growth on 2024 aluminium alloy at 70 °C, under 40 V, during 60 min, in 50 g L -1 di-sodium tetraborate solution containing di-sodium molybdate from 0.1 to 0.5 M (pH 10) is examined. Anodising behaviours strongly depend on additive concentration. Development of anodic films is favoured with weak molybdate additions (<0.3-0.4 M). The film thicknesses increase and the porosity of anodic layers decreases. Molybdenum (+VI), detected by X-ray photoelectron spectroscopy (XPS) analysis, is present in the anodic films and the Mo incorporation, studied by energy dispersive spectroscopy (EDS) analysis, increases with molybdate concentration. However, for high molybdate concentrations (>0.4 M), anodising behaviour becomes complex with the formation of a blue molybdenum oxide at the cathode. The growth of aluminium oxide is hindered. As the anodic layers are thinner, the Mo(+VI) incorporation significantly decreases. These two configurations implicate different corrosion performances in 5% sodium chloride solution at 35 °C. As the alkaline anodic layer formed with 0.3 M molybdate species is the thickest and the Mo incorporation is the more pronounced, its corrosion resistance is the highest. The effect of morphology and composition of anodic films on pitting corrosion is also discussed.

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

    PubMed

    Jastrzębska, Aneta; Kowalska, Sylwia; Szłyk, Edward

    2016-01-01

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

  5. Planar anchoring strength and pitch measurements in achiral and chiral chromonic liquid crystals using 90-degree twist cells

    NASA Astrophysics Data System (ADS)

    McGinn, Christine K.; Laderman, Laura I.; Zimmermann, Natalie; Kitzerow, Heinz-S.; Collings, Peter J.

    2013-12-01

    Chromonic liquid crystals are formed by molecules that spontaneously assemble into anisotropic structures in water. The ordering unit is therefore a molecular assembly instead of a molecule as in thermotropic liquid crystals. Although it has been known for a long time that certain dyes, drugs, and nucleic acids form chromonic liquid crystals, only recently has enough knowledge been gained on how to control their alignment so that studies of their fundamental liquid crystal properties can be performed. In this article, a simple method for producing planar alignment of the nematic phase in chromonic liquid crystals is described, and this in turn is used to create twisted nematic structures of both achiral and chiral chromonic liquid crystals. The optics of 90-degree twist cells allows the anchoring strength to be measured in achiral systems, which for this alignment technique is quite weak, about 3×10-7 J/m2 for both disodium cromoglycate and Sunset Yellow FCF. The addition of a chiral amino acid to the system causes the chiral nematic phase to form, and similar optical measurements in 90-degree twist cells produce a measurement of the intrinsic pitch of the chiral nematic phase. From these measurements, the helical twisting power for L-alanine is found to be (1.1±0.4)×10-2 μm-1 wt%-1 for 15 wt% disodium cromoglycate.

  6. Synthesis of phosphatidylcholine under possible primitive earth conditions

    NASA Technical Reports Server (NTRS)

    Rao, M.; Eichberg, J.; Oro, J.

    1982-01-01

    Using a primitive earth evaporating pond model, the synthesis of phosphatidylcholine was accomplished when a reaction mixture of choline chloride and disodium phosphatidate, in the presence of cyanamide and traces of acid, was evaporated and heated at temperatures ranging from 25 to 100 C for 7 hours. Optimum yields of about 15% were obtained at 80 C. Phosphatidylcholine was identified by chromatographic, chemical and enzymatic degradation methods. On enzymatic hydrolysis with phospholipase A2 and phospholipase C, lysophosphatidylcholine and phosphorylcholine were formed, respectively. Alkaline hydrolysis gave glycerophosphorylcholine. The synthesis of phosphatidylcholine as the major compound was accompanied by the formation of lysophosphatidylcholine in smaller amounts. Cyanamide was found to be essential for the formation of phosphatidylcholine, and only traces of HCl, of the order of that required to convert the disodium phosphatidate to free phosphatidic acid were found necessary for the synthesis. This work suggests that phosphatidylcholine, which is an essential component of most biological membranes, could have been synthesized on the primitive earth.

  7. Discovery of 7-Hydroxy-6-methoxy-2-methyl-3-(3,4,5- trimethoxybenzoyl)benzo[b]furan (BNC105), a Tubulin Polymerization Inhibitor with Potent Antiproliferative and Tumor Vascular Disrupting Properties

    PubMed Central

    Flynn, Bernard L.; Gill, Gurmit S.; Grobelny, Damian W.; Chaplin, Jason H.; Paul, Dharam; Leske, Annabell F.; Lavranos, Tina C.; Chalmers, David K.; Charman, Susan A.; Kostewicz, Edmund; Shackleford, David M.; Morizzi, Julia; Hamel, Ernest; Jung, M. Katherine; Kremmidiotis, Gabriel

    2011-01-01

    A structure–activity relationship (SAR) guided design of novel tubulin polymerization inhibitors has resulted in a series of benzo[b]furans with exceptional potency toward cancer cells and activated endothelial cells. The potency of early lead compounds has been substantially improved through the synergistic effect of introducing a conformational bias and additional hydrogen bond donor to the pharmacophore. Screening of a focused library of potent tubulin polymerization inhibitors for selectivity against cancer cells and activated endothelial cells over quiescent endothelial cells has afforded 7-hydroxy-6-methoxy-2-methyl-3-(3,4,5-trimethoxybenzoyl)benzo-[b]furan (BNC105, 8) as a potent and selective antiproliferative. Because of poor solubility, 8 is administered as its disodium phosphate ester prodrug 9 (BNC105P), which is rapidly cleaved in vivo to return the active 8. 9 exhibits both superior vascular disrupting and tumor growth inhibitory properties compared with the benchmark agent combretastatin A-4 disodium phosphate 5 (CA4P). PMID:21774499

  8. Tuning the photodriven electron transport within the columnar perylenediimide stacks by changing the π-extent of the electron donors.

    PubMed

    Supur, Mustafa; Fukuzumi, Shunichi

    2013-02-21

    Photodriven electron-transport properties of the self-assemblies of N,N'-di(2-(trimethylammoniumiodide)ethylene)perylenediimide stacks (TAIPDI)(n) with three electron donors, disodium 4,4'-bis(2-sulfonatostyryl)biphenyl (BSSBP, stilbene-420), sodium 9,10-dimethoxyanthracene-2-sulfonate (DANS) and disodium 6-amino-1,3-naphthalenedisulfonate (ANADS) have been studied in water. These electron donors vary in their π-extent to adjust the electronic coupling and the distance with the PDI stacks. Possessing the largest π-extent, BSSBP has strong π-π interactions as well as ionic interactions with (TAIPDI)(n). Instead of π-stacking with TAIPDI planes, DANS and ANADS, with a relatively small π-extent, are embedded in the side chains of TAIPDIs via ionic interactions, resulting in a distance increment from the aromatic TAIPDI cores. After excitation, the BSSBP-(TAIPDI)(n) system exhibits fast charge separation (0.70 ps) and relatively slow charge recombination (485 ps) due to intermolecular electron delocalization along the TAIPDI stacks. On the other hand, charge separation in DANS-(TAIPDI)(n) and ANADS-(TAIPDI)(n) occurs within 1.5 and 1.6 ns, respectively, calculated from the quenching of singlet excited states. The lifetimes of charge-separated states are determined to be 44 and 96 μs, at least 10(5) times slower than that of BSSBP-(TAIPDI)(n) due to remarkably improved electron transport throughout the (TAIPDI)(n).

  9. Molecularly imprinted polymers for histamine recognition in aqueous environment.

    PubMed

    Trikka, Foteini A; Yoshimatsu, Keiichi; Ye, Lei; Kyriakidis, Dimitrios A

    2012-11-01

    Molecularly imprinted polymers (MIP) for histamine using methacrylic acid were developed and recognition mechanisms were thoroughly characterized for the first time in this study. The binding affinity of imprinted polymer with structurally related compounds was studied in organic and aqueous media, at various conditions. In organic media, MIP was found to bind histamine two and six times more than ranitidine and fluoxetine, respectively, whereas higher selectivity was observed in the case of dimentidene or disodium cromoglycate. The specific binding sites of MIP recognized histamine over L-histidine in aqueous conditions, while higher affinity for histamine compared to ranitidine, disodium cromoglycate, putrescine and to a putrescine analogue was observed. A combination of NMR and UV spectroscopy analyses for investigation of imprinting and recognition properties revealed that strong specific interactions between the functional monomer and histamine in the prepolymerization and in the aqueous solutions were probably responsible for histamine recognition. The preparation of histamine MIPs and elucidation of imprinting and recognition mechanism may serve as useful insight for future application of MIPs.

  10. Comparison between conventional indirect competitive enzyme-linked immunosorbent assay (icELISA) and simplified icELISA for small molecules.

    PubMed

    Zhao, Jing; Li, Gang; Yi, Guo-Xiang; Wang, Bao-Min; Deng, Ai-Xing; Nan, Tie-Gui; Li, Zhao-Hu; Li, Qing X

    2006-06-30

    A simplified indirect competitive enzyme-linked immunosorbent assay (icELISA) for small molecules was established by modifying the procedure of conventional icELISA. The key change was that the analyte, antibody, and enzyme-labeled second antibody in the simplified icELISA were added in one step, whereas in conventional icELISA these reagents were added in two separate steps. Three small chemicals, namely zeatin riboside, glycyrrhetinic acid, and chlorimuron-ethyl, were used to verify the new assay format and compare the results obtained from conventional icELISA and simplified icELISA. The results indicated that, under optimized conditions, the new assay offered several advantages over the conventional icELISA, which are simpler, less time consuming and higher sensitive although it requires more amount of reagents. The assay sensitivity (IC50) was improved for 1.2-1.4-fold. Four licorice roots samples were analyzed by conventional icELISA and simplified icELISA, as well as liquid chromatography (LC). There was no significant difference among the content obtained from the three methods for each sample. The correlation between data obtained from conventional icELISA and simplified icELISA analyses was 0.9888. The results suggest that the simplified icELISA be useful for high throughput screening of small molecules.

  11. Lowering effect of phenolic glycosides on the rise in postprandial glucose in mice.

    PubMed

    Takii, H; Matsumoto, K; Kometani, T; Okada, S; Fushiki, T

    1997-09-01

    Glycosides were screened for their lowering effect on the postprandial blood glucose rise in vivo. The effect of phlorizin and other phenolic glycosides on the postprandial blood glucose response to glucose ingestion was evaluated in Std ddY mice. When phlorizin was simultaneously added, the peak blood glucose level was significantly decreased by 51% (p < 0.01) compared to vehicles following glucose ingestion by mice, while the blood insulin responses were generally similar. Screening experiments were conducted with different classes of phenolic glycosides added to a glucose solution. Reductions of 40-52% (p < 0.05) were observed in vehicles containing arbutin, 4-hydroxyphenyl-alpha-D-glucopyranoside (hydroquinone-alpha-glucoside) or glycyrrhizin, and of only 15-31% (not significant) in vehicles containing neohesperidin dihydrochalcone, glycyrrhetinic acid monoglucuronide, or 3,4-dimethoxyphenyl-beta-D-glucopyranoside. No lowering effect was observed in vehicles containing salicin. Since glycyrrhizin, arbutin, and hydroquinone-alpha-glucoside blunted to varying degrees the postprandial blood glucose rise following glucose ingestion, they may be useful adjuvants for the treatment of diabetic subjects.

  12. Synthesis of liver-targeting dual-ligand modified GCGA/5-FU nanoparticles and their characteristics in vitro and in vivo

    PubMed Central

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

    2013-01-01

    Nanoparticle drug delivery systems using polymers hold promise for clinical applications. We synthesized dual-ligand modified chitosan (GCGA) nanoparticles using lactic acid, glycyrrhetinic acid, and chitosan to target the liver in our previous studies. We then synthesized the GCGA/5-FU nanoparticles by conjugating 5-fluorouracil (5-FU) onto the GCGA nanomaterial, which had a mean particle size of 239.9 nm, a polydispersity index of 0.040, a zeta potential of +21.2 mV, and a drug loading of 3.90%. GCGA/5-FU nanoparticles had good slow release properties, and the release process could be divided into five phases: small burst release, gentle release, second burst release, steady release, and slow release. Inhibitory effects of GCGA/5-FU on tumor cells targeted the liver, and were time and dose dependent. GCGA nanoparticles significantly prolonged the efficacy of 5-FU on tumor cells, and alleviated the resistance of tumor cells to 5-FU. GCGA/5-FU nanoparticles were mostly concentrated in the liver, indicating that the GCGA nanoparticles were liver targeting. GCGA/5-FU nanoparticles significantly suppressed tumor growth in orthotopic liver transplantation mouse model, and improved mouse survival. PMID:24232303

  13. Qualitative/Chemical Analyses of Ankaferd Hemostat and Its Antioxidant Content in Synthetic Gastric Fluids

    PubMed Central

    Koluman, Ahmet; Akar, Nejat; Malkan, Umit Y.; Haznedaroglu, Ibrahim C.

    2016-01-01

    Introduction. Ankaferd hemostat (ABS) is the first topical haemostatic agent involving the red blood cell-fibrinogen interactions. The antihemorrhagic efficacy of ABS has been tested in controlled clinical trials. The drug induces the formation of an encapsulated complex protein web with vital erythroid aggregation. The aim of this study is to detect the essential toxicity profile and the antioxidant molecules inside ABS. Methods. The pesticides were analyzed by GC-MS and LC-MS. The determination by ICP-MS after pressure digestion was performed for the heavy metals. HPLC was used for the detection of mycotoxins. Dioxin Response Chemically Activated Luciferase Gene Expression method was used for the dioxin evaluation. TOF-MS and spectra data were evaluated to detect the antioxidants and other molecules. Results. TOF-MS spectra revealed the presence of several antioxidant molecules (including tocotrienols, vitamin E, tryptophan, estriol, galangin, apigenin, oenin, 3,4-divanillyltetrahydrofuran, TBHQ, thymol, BHA, BHT, lycopene, glycyrrhetinic acid, and tomatine), which may have clinical implications in the pharmacobiological actions of ABS. Conclusion. The safety of ABS regarding the presence of heavy metals, pesticides, mycotoxins, GMO and dioxins, and PCBs was demonstrated. Thus the present toxicological results indicated the safety of ABS. The antioxidant content of ABS should be investigated in future studies. PMID:26925418

  14. Low-intensity pulsed ultrasound (LIPUS) and cell-to-cell communication in bone marrow stromal cells.

    PubMed

    Sena, Kotaro; Angle, Siddhesh R; Kanaji, Arihiko; Aher, Chetan; Karwo, David G; Sumner, Dale R; Virdi, Amarjit S

    2011-07-01

    Low-intensity pulsed ultrasound (LIPUS) is an established therapy for fracture repair and has been used widely in the clinics, but its underlying mechanism of action remains unclear. The aim of the current research was to determine the effect of LIPUS on gap junctional cell-to-cell intercellular communication in rat bone marrow stromal cells (BMSC) in vitro and to determine whether the ability of BMSCs to communicate by gap junctions would affect their response to LIPUS. Single or daily-multiple LIPUS treatment at 1.5MHz, 30mW/cm(2), for 20min was applied to BMSC. We demonstrated that BMSC form functional gap junctions and single LIPUS treatment significantly increased the intracellular dye transfer between BMSC. In addition, activated phosphorylation of ERK1/2 and p38 by LIPUS stimulation was diminished when cells were treated with a gap junction inhibitor 18β-glycyrrhetinic acid (18β). We further demonstrated that 18β diminished the significant increase in alkaline phosphatase activity following LIPUS stimulation. These results suggest a potential role of gap junctional cell-to-cell intercellular communication on the effects of LIPUS in BMSC.

  15. Human dehydrogenase/reductase (SDR family) member 11 is a novel type of 17β-hydroxysteroid dehydrogenase.

    PubMed

    Endo, Satoshi; Miyagi, Namiki; Matsunaga, Toshiyuki; Hara, Akira; Ikari, Akira

    2016-03-25

    We report characterization of a member of the short-chain dehydrogenase/reductase superfamily encoded in a human gene, DHRS11. The recombinant protein (DHRS11) efficiently catalyzed the conversion of the 17-keto group of estrone, 4- and 5-androstenes and 5α-androstanes into their 17β-hydroxyl metabolites with NADPH as a coenzyme. In contrast, it exhibited reductive 3β-hydroxysteroid dehydrogenase activity toward 5β-androstanes, 5β-pregnanes, 4-pregnenes and bile acids. Additionally, DHRS11 reduced α-dicarbonyls (such as diacetyl and methylglyoxal) and alicyclic ketones (such as 1-indanone and loxoprofen). The enzyme activity was inhibited in a mixed-type manner by flavonoids, and competitively by carbenoxolone, glycyrrhetinic acid, zearalenone, curcumin and flufenamic acid. The expression of DHRS11 mRNA was observed widely in human tissues, most abundantly in testis, small intestine, colon, kidney and cancer cell lines. Thus, DHRS11 represents a novel type of 17β-hydroxysteroid dehydrogenase with unique catalytic properties and tissue distribution.

  16. Physiological role of gap-junctional hemichannels. Extracellular calcium-dependent isosmotic volume regulation.

    PubMed

    Quist, A P; Rhee, S K; Lin, H; Lal, R

    2000-03-06

    Hemichannels in the overlapping regions of apposing cells plasma membranes join to form gap junctions and provide an intercellular communication pathway. Hemichannels are also present in the nonjunctional regions of individual cells and their activity is gated by several agents, including calcium. However, their physiological roles are unknown. Using techniques of atomic force microscopy (AFM), fluorescent dye uptake assay, and laser confocal immunofluorescence imaging, we have examined the extracellular calcium-dependent modulation of cell volume. In response to a change in the extracellular physiological calcium concentration (1.8 to glycyrrhetinic acid, or were reversed by returning extracellular calcium to the normal level. We conclude that nongap-junctional hemichannels regulate cell volume in response to the change in extracellular physiological calcium in an otherwise isosmotic situation.

  17. Synthesis of molecularly imprinted polymers using acrylamide-β-cyclodextrin as a cofunctional monomer for the specific capture of tea saponins from the defatted cake extract of Camellia oleifera.

    PubMed

    Guo, Huiqin; Xiong, Jingjing; Ma, Wentian; Wu, Minghuo; Yan, Liushui; Li, Kexin; Liu, Yu

    2016-11-01

    Molecularly imprinted polymers were synthesized using mixed tea saponins as a template and acrylamide-β-cyclodextrin as a cofunctional monomer for the specific binding and purification of tea saponins from the defatted cake extract of Camellia oleifera. The adsorption properties of the prepared polymers were systematically evaluated including adsorption kinetics, adsorption isotherms, and selective recognition characteristics. It showed that the adsorption kinetics followed the pseudo first-order kinetic model (R(2) = 0.995) with an equilibrium time of 3 h, adsorption isotherm data fitted well with the Langmuir-Freundlich model (R(2) = 0.984) with an adsorption capacity of 14.23 mg/g. The relative selectivity coefficient (k´) in the presence of the analogues glycyrrhizic acid and glycyrrhetinic acid were 1.16 and 17.21, respectively. The performance of the molecularly imprinted polymers as solid-phase extraction materials was investigated and the results indicated that using acrylamide-β-cyclodextrin as a cofunctional monomer improved both the adsorption capacity and active sites stability of the imprinted polymers. The solid-phase extraction using the polymers as packing materials was subsequently applied for the separation of tea saponins in raw C. oleifera press extract, and targets were obtained with a purity reaching 89%.

  18. Anti-tubercular agents from Glycyrrhiza glabra.

    PubMed

    Kalani, Komal; Chaturvedi, Vinita; Alam, Sarfaraz; Khan, Feroz; Srivastava, Santosh Kumar

    2015-01-01

    Bioactivity guided isolation of Glycyrrhiza glabra (Leguminosae / Fabaceae) roots resulted in the characterization of 18β-glycyrrhetinic acid as a major anti-tubercular agent. Further, GA-1 was semi-synthetically converted into its nine derivatives, which were in-vitro evaluated for their antitubercular potential against Mycobacterium tuberculosis H37Rv using BACTEC-460 radiometric susceptibility assay. All the derivatives were active, but the benzylamide (GA-8, MIC 12.5μg/ml) and ethyl oxylate (GA-3, MIC 25.0 μg/ml) derivatives were significantly active against the pathogen. This was further supported by the molecular docking studies, which showed adequate docking (LibDock) scores for GA-3 (120.3) and GA-8 (112.6) with respect to the standard anti-tubercular drug, rifampicin (92.94) on the DNA-directed RNA polymerase subunit beta (rpoB) target site. Finally, the in silico pharmacokinetic and drug-likeness studies showed that GA-3 and GA- 8 possesses drug-like properties. This is the first ever report on the anti-tubercular potential of GA and its derivatives. These results may be of great help in anti-tubercular drug development from a very common, inexpensive, and non toxic natural product.

  19. MRP transporters as membrane machinery in the bradykinin-inducible export of ATP.

    PubMed

    Zhao, Yumei; Migita, Keisuke; Sun, Jing; Katsuragi, Takeshi

    2010-04-01

    Adenosine triphosphate (ATP) plays the role of an autocrine/paracrine signal molecule in a variety of cells. So far, however, the membrane machinery in the export of intracellular ATP remains poorly understood. Activation of B2-receptor with bradykinin-induced massive release of ATP from cultured taenia coli smooth muscle cells. The evoked release of ATP was unaffected by gap junction hemichannel blockers, such as 18alpha-glycyrrhetinic acid and Gap 26. Furthermore, the cystic fibrosis transmembrane regulator (CFTR) coupled Cl(-) channel blockers, CFTR(inh)172, 5-nitro-2-(3-phenylpropylamino)-benzoic acid, Gd3(+) and glibenclamide, failed to suppress the export of ATP by bradykinin. On the other, the evoked release of ATP was greatly reduced by multidrug resistance protein (MRP) transporter inhibitors, MK-571, indomethacin, and benzbromarone. From western blotting analysis, blots of MRP 1 protein only, but not MRP 2 and MRP 3 protein, appeared at 190 kD. However, the MRP 1 protein expression was not enhanced after loading with 1 muM bradykinin for 5 min. Likewise, niflumic acid and fulfenamic acid, Ca2(+)-activated Cl(-) channel blockers, largely abated the evoked release of ATP. The possibility that the MRP transporter system couples with Ca2(+)-activated Cl(-) channel activities is discussed here. These findings suggest that MRP transporters, probably MRP 1, unlike CFTR-Cl(-) channels and gap junction hemichannels, may contribute as membrane machinery to the export of ATP induced by G-protein-coupled receptor stimulation.

  20. Effects of Active Components of Fuzi and Gancao Compatibility on Bax, Bcl-2, and Caspase-3 in Chronic Heart Failure Rats

    PubMed Central

    Wang, Liqin; He, Yu; Zhang, Yuyan; Zhou, Huifen; Yu, Li

    2016-01-01

    Hypaconitine (HA) and glycyrrhetinic acid (GA) are active components of Fuzi (Aconitum carmichaelii) and Gancao (Glycyrrhiza uralensis Fisch); they have been used in compatibility for chronic heart failure (CHF) from ancient times. The purpose of the present research was to explore whether apoptosis pathways were related with the protective effects of HA + GA against CHF rats or not. The rats were progressed with transverse-aortic constriction (TAC) operation for 4 weeks to build the CHF state, and then the Digoxin (1 mg/kg), HA (2.07 mg/kg), GA (25 mg/kg), and HA (2.07 mg/kg) + GA (25 mg/kg) were orally administrated to rats for 1 week. The levels of BNP and cTnI in the plasma were decreased in the HA + GA group, and the heart/body weight ratio (H/B) and left ventricular (LV) parameters of transthoracic echocardiography were also declined; moreover, the expressions of Bax, Bcl-2, and caspase-3 were all improved in the HA + GA group than other groups in the immunohistochemistry and western blot methods. In general, the data suggested that Fuzi and Gancao compatibility could protect the CHF rats from apoptosis, which provided a strong evidence for further searching for mechanisms of them. PMID:28053643

  1. Self-assembly of renewable  nano-sized triterpenoids.

    PubMed

    Bag, Braja Gopal; Majumdar, Rakhi

    2017-02-14

    Studies on plant metabolites have gained renewed interest in recent years because these can serve as renewable chemicals for the development of a sustainable society. Among various plant secondary metabolites, terpenoids constitute the major component and triterpenoids are the 30C subset of it. In recent years, triterpenoids have drawn the attention of scientific community due to many of its potential and realized applications in medicine, drug delivery, thermochromic materials, pollutant capture, catalysis, liquid crystals, etc. In this personal review, we have discussed our computational results carried out on sixty representative naturally occurring triterpenoids demonstrating that all the triterpenoids are renewable functional nano-entities. Study of the self-assembly of several triterpenoids such as betulin, betulinic acid, oleanolic acid, glycyrrhetinic acid and arjunolic acid and their derivatives in different liquids have also been discussed. Moreover, the utilization of the resulting supramolecular architectures such as vesicles, spheres, flowers and fibrillar networks of nano- to micrometer dimensions and gels have also been discussed in the perspective of green, renewable and nanos.

  2. Treatment of pruritus in mild-to-moderate atopic dermatitis with a topical non-steroidal agent.

    PubMed

    Veraldi, Stefano; De Micheli, Paolo; Schianchi, Rossana; Lunardon, Luisa

    2009-06-01

    Atopiclair (Zarzenda) is a topical non-steroidal anti-inflammatory agent for the treatment of allergic diseases of the skin. Three main ingredients are contained in this product: glycyrrhetinic acid, telmesteine and Vitis vinifera extracts. Other ingredients include: allantoin, alpha-bisabolol, capryloyl glycine, hyaluronic acid, shea butter and tocopheryl acetate. Two previous randomized, double-blind, vehicle-controlled clinical studies provided evidence that Atopiclair is effective in the treatment of atopic dermatitis. This article presents an open, multicenter, sponsor-free, study on the anti-pruritic activity of this product in adult patients with mild-to-moderate atopic dermatitis. The Median Visual Analogue Scale (VAS) values were: at the start of the study (TO), median VAS was 48.5 mm; three weeks later (T1), median VAS was 34.1 mm (-14.4 mm from baseline); six weeks later (T2), median VAS was 24.6 mm (-23.9 mm from baseline). Statistical analysis revealed that differences between TO versus T1, TO versus T2 and T1 versus T2 were highly significant (p<0.001). Side effects (local burning) were relatively common, although mild in severity. On the basis of the results of this study, Atopiclair showed efficacy in relief of pruritus in adult patients with mild-to-moderate atopic dermatitis.

  3. UHPLC-MS/MS quantification combined with chemometrics for the comparative analysis of different batches of raw and wine-processed Dipsacus asper.

    PubMed

    Tao, Yi; Du, Yingshan; Su, Dandan; Li, Weidong; Cai, Baochang

    2017-02-20

    A rapid and sensitive ultra high performance liquid chromatography with tandem mass spectrometry approach was established for the simultaneous determination of 4-caffeoylquinic acid, loganic acid, chlorogenic acid, loganin, 3,5-dicaffeoylquinic acid, dipsacoside B, asperosaponin VI and sweroside in raw and wine-processed Dipsacus asper. Chloramphenicol and glycyrrhetinic acid were employed as internal standards. The proposed approach was fully validated in terms of linearity, sensitivity, precision, repeatability as well as recovery. Intra- and inter-assay variability for all analytes were 2.8-4.9 and 1.7-4.8%, respectively. The standard addition method determined recovery rates for each analytes (96.8-104.6%). In addition, the developed approach was applied to 20 batches of raw and wine-processed samples of Dipsacus asper. Principle component analysis and partial least squares-discriminate analysis revealed a clear separation between the raw group and wine-processed group. After wine-processing, the contents of loganic acid, chlorogenic acid, dipsacoside B and asperosaponin VI were up-regulated, whilst the contents of 3,5-dicaffeoylquinic acid, 4-caffeoylquinic acid, loganin and sweroside were down-regulated. Our results demonstrated that ultra high performance liquid chromatography with tandem mass spectrometry quantification combined with chemometrics is a viable method for quality evaluation of the raw Dipsacus asper and its wine-processed products. This article is protected by copyright. All rights reserved.

  4. Strain uses gap junctions to reverse stimulation of osteoblast proliferation by osteocytes

    PubMed Central

    Suswillo, Rosemary F.L.; Rawlinson, Simon C.F.; Dowthwaite, Gary P.; Lanyon, Lance E.; Pitsillides, Andrew A.

    2017-01-01

    Identifying mechanisms by which cells of the osteoblastic lineage communicate in vivo is complicated by the mineralised matrix that encases osteocytes, and thus, vital mechanoadaptive processes used to achieve load‐bearing integrity remain unresolved. We have used the coculture of immunomagnetically purified osteocytes and primary osteoblasts from both embryonic chick long bone and calvariae to examine these mechanisms. We exploited the fact that purified osteocytes are postmitotic to examine both their effect on proliferation of primary osteoblasts and the role of gap junctions in such communication. We found that chick long bone osteocytes significantly increased basal proliferation of primary osteoblasts derived from an identical source (tibiotarsi). Using a gap junction inhibitor, 18β‐glycyrrhetinic acid, we also demonstrated that this osteocyte‐related increase in osteoblast proliferation was not reliant on functional gap junctions. In contrast, osteocytes purified from calvarial bone failed to modify basal proliferation of primary osteoblast, but long bone osteocytes preserved their proproliferative action upon calvarial‐derived primary osteoblasts. We also showed that coincubated purified osteocytes exerted a marked inhibitory action on mechanical strain–related increases in proliferation of primary osteoblasts and that this action was abrogated in the presence of a gap junction inhibitor. These data reveal regulatory differences between purified osteocytes derived from functionally distinct bones and provide evidence for 2 mechanisms by which purified osteocytes communicate with primary osteoblasts to coordinate their activity. PMID:28083967

  5. Functional assessment of gap junctions in monolayer and three-dimensional cultures of human tendon cells using fluorescence recovery after photobleaching

    NASA Astrophysics Data System (ADS)

    Kuzma-Kuzniarska, Maria; Yapp, Clarence; Pearson-Jones, Thomas W.; Jones, Andrew K.; Hulley, Philippa A.

    2014-01-01

    Gap junction-mediated intercellular communication influences a variety of cellular activities. In tendons, gap junctions modulate collagen production, are involved in strain-induced cell death, and are involved in the response to mechanical stimulation. The aim of the present study was to investigate gap junction-mediated intercellular communication in healthy human tendon-derived cells using fluorescence recovery after photobleaching (FRAP). The FRAP is a noninvasive technique that allows quantitative measurement of gap junction function in living cells. It is based on diffusion-dependent redistribution of a gap junction-permeable fluorescent dye. Using FRAP, we showed that human tenocytes form functional gap junctions in monolayer and three-dimensional (3-D) collagen I culture. Fluorescently labeled tenocytes following photobleaching rapidly reacquired the fluorescent dye from neighboring cells, while HeLa cells, which do not communicate by gap junctions, remained bleached. Furthermore, both 18 β-glycyrrhetinic acid and carbenoxolone, standard inhibitors of gap junction activity, impaired fluorescence recovery in tendon cells. In both monolayer and 3-D cultures, intercellular communication in isolated cells was significantly decreased when compared with cells forming many cell-to-cell contacts. In this study, we used FRAP as a tool to quantify and experimentally manipulate the function of gap junctions in human tenocytes in both two-dimensional (2-D) and 3-D cultures.

  6. Roles of phytochemicals in amino acid nutrition.

    PubMed

    Kong, Xiangfeng; Wu, Guoyao; Yin, Yinlong

    2011-01-01

    Chinese herbal medicine (CHM) is often used as dietary supplements to maintain good health in animals and humans. Here, we review the current knowledge about effects of CHM (including ultra-fine Chinese herbal powder, Acanthopanax senticosus extracts, Astragalus polysaccharide, and glycyrrhetinic acid) as dietary additives on physiological and biochemical parameters in pigs, chickens and rodents. Additionally, we propose possible mechanisms for the beneficial effects of CHM on the animals. These mechanisms include (a) increased digestion and absorption of dietary amino acids; (b) altered catabolism of amino acids in the small intestine and other tissues; (c) enhanced synthesis of functional amino acids (e.g., arginine, glutamine and proline) and polyamines; and (d) improved metabolic control of nutrient utilization through cell signaling. Notably, some phytochemicals and glucocorticoids share similarities in structure and physiological actions. New research findings provide a scientific and clinical basis for the use of CHM to improve well-being in livestock species and poultry, while enhancing the efficiency of protein accretion. Results obtained from animal studies also have important implications for human nutrition and health.

  7. GABAergic responses of mammalian ependymal cells in the central canal neurogenic niche of the postnatal spinal cord.

    PubMed

    Corns, Laura F; Deuchars, Jim; Deuchars, Susan A

    2013-10-11

    The area surrounding the central canal of the postnatal mammalian spinal cord is a highly plastic region that exhibits many similarities to other postnatal neurogenic niches, such as the subventricular zone. Within this region, ependymal cells have been identified as neural stem cells however very little is known about their properties and how the local environment, including neurotransmitters, is capable of affecting them. The neurotransmitter GABA is present around the central canal and is known to affect cells within other postnatal neurogenic niches. This study used whole cell patch clamp electrophysiology and intracellular dye-loading in in vitro Wistar rat spinal cord slices to characterise ependymal cells and their ability to respond to GABA. Ependymal cells were defined by their passive response properties and low input resistances. Extensive dye-coupling was observed between ependymal cells; this was confirmed as gap junction coupling using the gap junction blocker, 18β-glycyrrhetinic acid, which significantly increased the input resistance of ependymal cells. GABA depolarised all ependymal cells tested; the partial antagonism of this response by bicuculline and gabazine indicates that GABA(A) receptors contribute to this response. A lack of effect by baclofen suggests that GABA(B) receptors do not contribute to the GABAergic response. The ability of ependymal cells to respond to GABA suggests that GABA could be capable of influencing the proliferation and differentiation of cells within the neurogenic niche of the postnatal spinal cord.

  8. Mechanical signaling coordinates the embryonic heartbeat

    PubMed Central

    Chiou, Kevin K.; Rocks, Jason W.; Chen, Christina Yingxian; Cho, Sangkyun; Merkus, Koen E.; Rajaratnam, Anjali; Robison, Patrick; Tewari, Manorama; Vogel, Kenneth; Majkut, Stephanie F.; Prosser, Benjamin L.; Discher, Dennis E.; Liu, Andrea J.

    2016-01-01

    In the beating heart, cardiac myocytes (CMs) contract in a coordinated fashion, generating contractile wave fronts that propagate through the heart with each beat. Coordinating this wave front requires fast and robust signaling mechanisms between CMs. The primary signaling mechanism has long been identified as electrical: gap junctions conduct ions between CMs, triggering membrane depolarization, intracellular calcium release, and actomyosin contraction. In contrast, we propose here that, in the early embryonic heart tube, the signaling mechanism coordinating beats is mechanical rather than electrical. We present a simple biophysical model in which CMs are mechanically excitable inclusions embedded within the extracellular matrix (ECM), modeled as an elastic-fluid biphasic material. Our model predicts strong stiffness dependence in both the heartbeat velocity and strain in isolated hearts, as well as the strain for a hydrogel-cultured CM, in quantitative agreement with recent experiments. We challenge our model with experiments disrupting electrical conduction by perfusing intact adult and embryonic hearts with a gap junction blocker, β-glycyrrhetinic acid (BGA). We find this treatment causes rapid failure in adult hearts but not embryonic hearts—consistent with our hypothesis. Last, our model predicts a minimum matrix stiffness necessary to propagate a mechanically coordinated wave front. The predicted value is in accord with our stiffness measurements at the onset of beating, suggesting that mechanical signaling may initiate the very first heartbeats. PMID:27457951

  9. Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation.

    PubMed

    Andrikopoulos, Nikolaos K; Kaliora, Andriana C; Assimopoulou, Andreana N; Papapeorgiou, Vassilios P

    2003-05-01

    Naturally occurring gums and resins with beneficial pharmaceutical and nutraceutical properties were tested for their possible protective effect against copper-induced LDL oxidation in vitro. Chiosmastic gum (CMG) (Pistacia lentiscus var. Chia resin) was the most effective in protecting human LDL from oxidation. The minimum and maximum doses for the saturation phenomena of inhibition of LDL oxidation were 2.5 mg and 50 mg CMG (75.3% and 99.9%, respectively). The methanol/water extract of CMG was the most effective compared with other solvent combinations. CMG when fractionated in order to determine a structure-activity relationship showed that the total mastic essential oil, collofonium-like residue and acidic fractions of CMG exhibited a high protective activity ranging from 65.0% to 77.8%. The other natural gums and resins (CMG resin 'liquid collection', P. terebinthus var. Chia resin, dammar resin, acacia gum, tragacanth gum, storax gum) also tested as above, showed 27.0%-78.8% of the maximum LDL protection. The other naturally occurring substances, i.e. triterpenes (amyrin, oleanolic acid, ursolic acid, lupeol, 18-a-glycyrrhetinic acid) and hydroxynaphthoquinones (naphthazarin, shikonin and alkannin) showed 53.5%-78.8% and 27.0%-64.1% LDL protective activity, respectively. The combination effects (68.7%-76.2% LDL protection) of ursolic-, oleanolic- and ursodeoxycholic- acids were almost equal to the effect (75.3%) of the CMG extract in comparable doses.

  10. Influence of certain ingredients on the SPF determined in vivo.

    PubMed

    Couteau, Céline; Chauvet, Catherine; Paparis, Eva; Coiffard, Laurence J M

    2012-12-01

    When determined in vitro, the SPF of certain commercial sunscreen products can be lower than the SPF indicated on the label. The study of the composition of this type of product enabled us to note that the majority contained substances reputed to have anti-inflammatory properties. This effect is shown by inhibiting the erythema, without protecting the skin, which constitutes a serious public health problem. The anti-inflammatory effects of αbisabolol-, allantoin- and 18-β-glycyrrhetinic acid-based emulsions, as well as commercial sun products containing any one of these molecules, have been tested with phorbol myristate acetate on mice. The effectiveness of these sunscreens products is quantified using two indicators: SPF (sun protection factor) and PF-UVA (protection factor-UVA) by in vitro method. We were thus able to show that certain sun products have an anti-inflammatory effect, which in turn causes the SPF value shown on the product to be overestimated, indeed sometimes by considerably large margins.

  11. Cardiovascular action of a new carbenoxolone derivative.

    PubMed

    Filczewski, M; Kosmala, M; Oledzka, K

    1988-01-01

    The circulatory effects of oleanoic acid sodium hydrogen succinate (OSS), an analogue of the anti-ulcer drug, carbenoxolone, were investigated. As carbenoxolone produces such adverse effects as sodium retention and a subsequent elevation of the arterial blood pressure in man, the present study was aimed at determining whether OSS is similar or different from it in this respect. Carbenoxolone, (43,3 mg/kg po) and OSS (66,6 mg/kg po) were given to rats twice daily for 4 weeks. The systolic blood pressure was elevated already after the first week of treatment. The hypertension was accompanied by bradycardia, which increased with the time of treatment. In the blood an increase in the creatinine level, a decrease in the urea level, and a slight elevation in sodium concentration were found after the treatment, while the potassium concentration during the whole treatment period (4 weeks) remained unchanged. Although the principal aldosterone-like effects of carbenoxolone were attributed to the oxygen presence in position 11 of the glycyrrhetinic acid ring, [8], the absence of an oxygen at that position in OSS did not cause the loss of the adverse circulatory effect.

  12. Hemichannels formed by connexin 43 play an important role in the release of prostaglandin E(2) by osteocytes in response to mechanical strain.

    PubMed

    Jiang, Jean X; Cherian, Priscilla P

    2003-01-01

    Osteocytes embedded in the matrix of bone are mechanosensory cells that translate strain into signals and regulate bone remodeling. Our previous studies using osteocyte-like MLO-Y4 cells have shown that fluid flow shear stress (FFSS) increases connexin (Cx) 43 protein expression, prostaglandin E(2) (PGE(2)) release, and intercellular coupling, and PGE(2) is an essential mediator between FFSS and gap junctions. However, the role of Cx43 in the release of PGE(2) in response to FFSS is unknown. Here, the FFSS-loaded MLO-Y4 cells with no or few intercellular channels released significantly more PGE(2) per cell than those cells at higher densities. Antisense Cx43 oligonucleotides and 18 beta-glycyrrhetinic acid, a specific gap junction and hemichannel blocker, significantly reduced PGE(2) release by FFSS at all cell densities tested, especially cells at the lowest density without gap junctions. FFSS, fluid flow-conditioned medium, and PGE(2) increased the activity of dye uptake. Moreover, FFSS induced Cx43 to migrate to the surface of the cell; this surface expressed Cx43 developed resistance to Triton-X-100 solublization. Our results suggest that hemichannels formed by Cx43, instead of intercellular channels, are likely to play a predominant role in the release of intracellular PGE(2) in response to FFSS.

  13. Shieldable tumor targeting based on pH responsive self-assembly/disassembly of gold nanoparticles.

    PubMed

    Tian, Zhiqing; Yang, Chengling; Wang, Wei; Yuan, Zhi

    2014-10-22

    A new approach to shield/deshield ligands for controllable tumor targeting was reported, which was based on amphiphilic self-assembly and disassembly of gold nanoparticles (Au NPs). Thanks to the excellent pH response of the system, glycyrrhetinic acid (GA) ligands can be buried inside the Au NPs' assembly at normal tissue pH (pH 7.4), while exposed when the nanostructure is disassembled at tumor extracellular pH (pHe 6.8). Hydrophobic GA molecules not only acted as ligands targeting tumor cells but also provided the major interparticle attractive force for Au NPs' assembling. An ordered assembly of Au NPs with regular shape, proper size and ultrasharp pH sensitivity (ΔpH ∼ 0.2) was achieved by fine-tuning of materials modified on Au NPs. Mechanism studies for assembly and disassembly of Au NPs indicated the possibility of a GA shield when the assembly formed, which was further demonstrated by bovine serum albumin absorption and cellular uptake. The assembly/disassembly process was reversible within extrinsic pH changes, which provides a perspective for reversible tumor targeting.

  14. Simultaneous determination of oleanolic acid, p-coumaric acid, ferulic acid, kaemperol and quercetin in rat plasma by LC-MS-MS and application to a pharmacokinetic study of Oldenlandia diffusa extract in rats.

    PubMed

    Li, Neng; Liu, Changhui; Mi, Suiqing; Wang, Ningsheng; Zheng, Xia; Li, Yingyi; Huang, Xiaotao; He, Shaoling; Chen, Hao; Xu, Xinhua

    2012-01-01

    A simple, rapid and sensitive liquid chromatography tandem mass spectrometry method is presented for the simultaneous determination of oleanolic acid, p-coumaric acid, ferulic acid, kaemperol and quercetin in rat plasma. Glycyrrhetinic acid was used as an internal standard, and sample pretreatment consisted of a liquid-liquid extraction. Chromatographic separation was achieved on a Gemini 110A C18 column (50 × 2.0 mm i.d., 5 µm) by gradient elution with a mobile phase consisting of methanol, acetonitrile and 0.01% formic acid in water. Tandem mass spectrometric detection was conducted using multiple reaction monitoring under negative ionization mode. Calibration curves offered linear ranges of two orders of magnitude with r > 0.99. The method was validated in terms of matrix effect, intra-day and inter-day precision, accuracy, linearity, specificity and stability. The relative standard deviation of intra-day and inter-day variations ranged from 2.66 to 14.74% and 1.9 to 14.55%. No substantial endogenous interference from blank plasma was observed. The method has been successfully applied to a pharmacokinetic study of Oldenlandia diffusa extract after oral administration in rats.

  15. Use of potassium chloride and flavor enhancers in low sodium Cheddar cheese.

    PubMed

    Grummer, J; Bobowski, N; Karalus, M; Vickers, Z; Schoenfuss, T

    2013-03-01

    We investigated use of potassium chloride (KCl) to maintain both the salty flavor and to replace the preservative effects of salt when reducing the sodium content in natural cheese. Because salt replacers can affect flavor because of inherent off-flavors, such as bitter and metallic, we examined the use of flavor enhancers for their ability to modulate some of these undesirable sensory effects. Stirred-curd Cheddar-style cheese was manufactured using 2 cheese-making procedures (different curd knife sizes and target salting titratable acidities), in duplicate. Curd was salted with sodium chloride (NaCl) or 60% reduced sodium blends of NaCl and KCl (2 different sources). Curd was also salted at a 60% reduced sodium rate with NaCl and KCl with added flavor enhancers. A hydrolyzed vegetable protein/yeast extract blend, a natural "potassium-blocking type" flavor, disodium inosinate, or disodium guanylate were each blended with the reduced sodium salt blend and added to curd at the salting step. The resulting blocks of cheese were aged for 5 mo and evaluated monthly for chemical, microbial, and sensory differences. At 5 mo of aging, we measured liking for the cheeses using a consumer panel. Overall, cheeses were well liked by the consumer panel, and the scores of reduced sodium cheese with 2 different KCl sources were not different from those of the full-sodium control. The addition of flavor enhancers to Cheddar curd had mixed results, with one improving the consumer flavor liking only slightly over KCl, and one (disodium inosinate) significantly reducing consumer flavor liking scores, presumably due to the amount of umami flavor it contributed. Potassium chloride replacement salts sourced from different manufacturers affected the chemical and flavor properties of cheese, and changes to pH and temperature targets may be necessary to yield cheese with the moisture and pH targets desired. The cheese-making procedure used also influenced flavors observed, which resulted in

  16. Porous cellulose spheres: Preparation, modification and adsorption properties.

    PubMed

    Ma, Xiaofei; Liu, Congzhi; Anderson, Debbie P; Chang, Peter R

    2016-12-01

    Porous cellulose spheres (PCS) were fabricated by precipitating the spheres from a cellulose ionic liquid solution, followed by freezing, solvent exchange, and drying. PCS had low crystallinity and a large surface area that facilitated modification with trisodium trimetaphosphate (STMP) to introduce phosphate ester groups into the porous structure of the heterogeneous system. The STMP-modified PCS (SPCS) were used to remove heavy metal ions from aqueous solution. With increasing STMP dosage, the adsorption capacity of SPCS obviously improved due to chelation between Pb(2+) and phosphate ester groups. The kinetic adsorption and isotherm data matched the pseudo-second order model and the Langmuir model well. The maximum adsorption capacity reached 150.6 mg g(-1) for SPCS. SPCS were competitive with other absorbents because the phosphate ester groups and porous structure contributed to Pb(2+) adsorption. Moreover, SPCS can be regenerated with ethylenediamine tetraacetic acid disodium salt (EDTA) solution for repetitious adsorption of Pb(2+).

  17. Two-Point Particle Tracking Microrheology of Nematic Lyotropic Liquid Crystals

    NASA Astrophysics Data System (ADS)

    Gomez-Gonzalez, Manuel; Del Alamo, Juan Carlos

    2016-11-01

    Biological and technological complex fluids that are usually available in microscopic amounts (e.g. liquid crystals and biopolymer networks) can exhibit microstructural order leading to nematic rheological behavior. However, current microrheological methods cannot measure their directional viscoelastic coefficients. We recently introduced a directional two-point particle-tracking microrheology (D2PTM) technique to determine these coefficients (1). Here, we experimentally validate D2PTM by applying this method to disodium cromoglycate (DSCG), a lyotropic chromonic nematic liquid crystal that has recently sparked attention due to its biocompatibility and other interesting properties. We chose DSCG because its directional viscosity coefficients have been previously characterized by dynamic light scattering and are available in the literature. Our results suggest that D2PTM measurements agree well with measurements from previous methods. Furthermore, this new technique provides additional information about the microrheological response of nematic fluids that was not accessible via previous methods.

  18. Novel method for the preparation of core-shell nanoparticles with movable Ag core and polystyrene loop shell

    SciTech Connect

    Liu Weijun; Zhang Zhicheng . E-mail: lwj3600@ustc.edu; He Weidong; Zheng Cheng; Ge Xuewu; Li, Jian; Liu Huarong; Jiang Hao

    2006-04-15

    Core/shell nanoparticles with movable silver (Ag) core and polystyrene (PSt) shell (Ag at PSt nanoparticle) were successfully synthesized at room temperature and under ambient pressure via two steps: {gamma}-irradiation and interfacial-initiated polymerization. Firstly, mono-dispersed Ag nanoparticles with diameters 20 nm were synthesized in inversed microemulsion by reducing silver nitrate under {gamma}-irradiation. Then, Ag nanoparticles were coated with PSt via interfacial-initiated polymerization with cumene hydroperoxide/ferrous sulfate/disodium ethylenediaminetetraacetate/sodium formaldehyde sulfoxylate (CHPO-Fe {sup 2+}-EDTA-SFS) as the redox initiation pair. The resulted Ag at PSt nanoparticles were identified by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS)

  19. Same-day batch measurement of glycine betaine, carnitine, and other betaines in biological material.

    PubMed

    Lever, M; Bason, L; Leaver, C; Hayman, C M; Chambers, S T

    1992-08-15

    Glycine betaine, carnitine, carnitine esters, butyrobetaine, and proline betaine (stachydrine) concentrations in biological materials can be reliably measured in 100-microliters samples, with a detection limit below 1 mumol/liter. The procedure is suitable for batches of more than 30 specimens and it is possible to obtain a single result within 2 h. The betaines are extracted into an acetonitrile:methanol mixture, dried with anhydrous disodium hydrogen phosphate containing argentous oxide. The 4-bromophenacyl ester derivatives are formed using 4-bromophenacyl triflate as reagent, in the presence of solid magnesium oxide as base. The derivatives are separated by high-performance chromatography on a silica column, in a mixed partition and ion-exchange mode.

  20. New platinum compounds containing the diphosphine ligand 2-(ferrocenylidene)-4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (fbpcd): Synthesis, redox behavior, and X-ray diffraction structures Of PtCl2(fbpcd) and Pt(mnt)(fbpcd)

    SciTech Connect

    Poola, Bhaskar; Hunt, Sean W; Wang, Xiaoping; Richmond, Michael G.

    2008-01-01

    The reaction of the redox-active diphosphine ligand 2-(ferrocenylidene)-4,5-bis(diphenylphosphino)-4-cyclopenten-1,3-dione (fbpcd) with PtCl2(1,5-cod) furnishes the platinum(II) compound PtCl2(fbpcd) (2). Treatment of 2 with disodium maleonitriledithiolate (Na(2)mnt) yields the chelating thiolate compound Pt(mnt)(fbpcd) (3). Both 2 and 3 have been fully characterized in solution by IR, UV-Vis, and NMR spectroscopies, and their molecular structures established by X-ray crystallography. The redox properties of the fbpcd ligand and compounds 2 and 3 have been investigated by cyclic voltammetry, and the composition of the HOMO and LUMO levels in these systems have been determined by extended Huckel MO calculations, the results of which are discussed with respect to electrochemical data.

  1. Design of a Flow-Through Voltammetric Sensor Based on an Antimony-Modified Silver Electrode for Determining Lithol Rubine B in Cosmetics

    PubMed Central

    Lai-Hao, Wang; Shu-Juan, Huang

    2011-01-01

    Lithol Rubine B (LRB; the disodium salt of 3-hydroxy-4-[(4-methyl-2-sulfophenyl) azo]-2-naphthalenecarboxylic acid) was detected using high-performance liquid chromatography with an electrochemical (antimony film on silver) detector (HPLC-ECD). For direct current (DC) mode, with the current at a constant potential, and measurements with suitable experimental parameters, a linear concentration from 0.125 to 1.80 μg/mL was found. The detection limit of our method was approximately 2.0 ng/mL. An antimony-modified silver detector was used to demonstrate that LRB is electrochemically reduced in acidic media and to analyze commercial cosmetics to determine their LRB content. Findings using HPLC-ECD and HPLC with an ultraviolet detector were comparable. PMID:21603230

  2. Cerebral mast cells contribute to postoperative cognitive dysfunction by promoting blood brain barrier disruption.

    PubMed

    Zhang, Susu; Dong, Hongquan; Zhang, Xiang; Li, Nana; Sun, Jie; Qian, Yanning

    2016-02-01

    Trauma induced neuroinflammation plays a key role in the development of postoperative cognitive dysfunction (POCD). The blood-brain barrier (BBB), a highly specialized endothelial layer, is exquisitely sensitive to inflammatory insults, which can result in numerous neurocognitive syndromes. While brain mast cells are the "first responder" in the injury, the functional interactions between mast cells and the BBB remain poorly understood. Our results demonstrate that tibial fracture surgery can induce cognitive impairment relating to an inflammatory response and destabilization of the BBB. Disodium cromoglycate (cromolyn)--which acts as a mast cell stabilizer--inhibited this effect. Specifically, cromolyn resulted in ameliorated cognitive ability, decrease of inflammatory cytokines and increase of BBB stability. Taken together, these results suggest that activated mast cells contributed to central nervous system inflammation and cognitive dysfunction by promoting BBB disruption, and interactions between mast cells and the BBB could constitute a new and unique therapeutic target for POCD.

  3. Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism–dystonia

    PubMed Central

    Tuschl, Karin; Meyer, Esther; Valdivia, Leonardo E.; Zhao, Ningning; Dadswell, Chris; Abdul-Sada, Alaa; Hung, Christina Y.; Simpson, Michael A.; Chong, W. K.; Jacques, Thomas S.; Woltjer, Randy L.; Eaton, Simon; Gregory, Allison; Sanford, Lynn; Kara, Eleanna; Houlden, Henry; Cuno, Stephan M.; Prokisch, Holger; Valletta, Lorella; Tiranti, Valeria; Younis, Rasha; Maher, Eamonn R.; Spencer, John; Straatman-Iwanowska, Ania; Gissen, Paul; Selim, Laila A. M.; Pintos-Morell, Guillem; Coroleu-Lletget, Wifredo; Mohammad, Shekeeb S.; Yoganathan, Sangeetha; Dale, Russell C.; Thomas, Maya; Rihel, Jason; Bodamer, Olaf A.; Enns, Caroline A.; Hayflick, Susan J.; Clayton, Peter T.; Mills, Philippa B.; Kurian, Manju A.; Wilson, Stephen W.

    2016-01-01

    Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism–dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates. PMID:27231142

  4. Artificially controlled degradable inorganic nanomaterial for cancer theranostics.

    PubMed

    Liu, Yuxin; Zhang, Ge; Guo, Quanwei; Ma, Liyi; Jia, Qi; Liu, Lidong; Zhou, Jing

    2017-01-01

    Multifunctional nanomaterials for cancer diagnosis and therapy have recently prompted widespread concern. To avoid nanotoxicity, the development of novel degradable functional materials must be our main focus. In this study, we firstly developed ethylenediaminetetraacetic acid calcium disodium salt (EDTA)- and bovine serum albumin (BSA)-capped Mn3O4 nanoparticles (MONPs-BSA-EDTA) as a novel inorganic nanomaterials for multifunctional imaging-guided photothermal therapy, which can be degraded in a progress-controlled way by artificially introduced ascorbic acid. The degradation products can also be captured and their excretion accelerated. Careful studies suggested that the toxicity of the MONPs-BSA-EDTA and its degradation products is low. The degradation mechanism also suggests a new method of controlled drug release. The development of artificially controlled degradable inorganic nanomaterials also provides a new way to degrade nanomaterials and minimize ion release, which may have potential applications in cancer theranostics without nanotoxicity.

  5. Synthesis, structure and magnetic properties of 5-(4-Sulfophenylazo) salicylate-bridged 1D coordination polymers containing linear trinuclear metal clusters

    NASA Astrophysics Data System (ADS)

    Liu, Hong; Song, Li-jun; Ju, Zhan-feng; Li, Wei; Zhang, Jie

    2008-03-01

    Three new trinuclear metal complexes with an azobenzene-containing ligand [M 3(Sasa) 2(Py) 2(H 2O) 8] (Na 2HSasa = 5-(4-Sulfophenylazo) salicylic acid disodium salt; Py = pyridine; M = Cu, Co, Zn), are synthesized through the interface diffusion and structurally characterized by single crystal X-ray diffraction, XRPD analysis and spectral methods. The metal ions in distorted octahedral coordination environments are connected by Sasa ligands to form 1D coordination polymer chain containing the linear trinuclear units with single syn-anti carboxylate bridges. The extensive hydrogen bonding interactions hold these chains together into 3D supramolecular network. Weak antiferromagnetic interactions between adjacent metal ions with J = -1.85 cm -1 and J = -2.81 cm -1 dominate the magnetic properties of Cu(II) and Co(II) complexes, separately.

  6. The significance of inhibitor-resistant alkaline phosphatase in the cytochemical demonstration of transport adenosine triphosphatase.

    PubMed

    Firth, J A; Marland, B Y

    1975-08-01

    The hydrolysis of disodium p-nitrophenyl phosphate at pH 9.0 by slices of formaldehydee-fixed rat renal cortex was investigated by colorimetric estimation of the nitrophenol liberated. It was found that three types of activity could be identified on the basis of their responses to inhibitors and cations: (a) alkaline phosphatase sensitive to inhibition by L-tetramisole; (b) potassium-dependent phosphatase, probably identifiable with the phosphatase component of sodium-potassium-dependent transport adenosine triphosphatase (?Na-K-ATPase); and (c) alkaline phosphatase insensitive to L-tetramisole. It was found that in the presence of strontium ions, as used in Na-K-ATPase cytochemistry, the activities of the second and third types of enzyme were approximately equal. The implications of these findings for the cytochemical demonstration of Na-K-ATPase are discussed.

  7. Chemiluminescent assay of enzymes using proenhancers and pro-anti-enhancers.

    PubMed

    Kricka, L J; Schmerfeld-Pruss, D; Edwards, B

    1991-01-01

    Enhanced chemiluminescent assays for hydrolase enzymes have been developed using proenhancer and pro-anti-enhancer substrates. Alkaline phosphatase is measured using disodium para-iodophenyl phosphate (proenhancer) which is converted to para-iodophenol and this in turn enhances the light emission from the horseradish peroxidase catalysed chemiluminescent oxidation of luminol by peroxide. An alternative strategy uses para-nitrophenyl phosphate which is converted by alkaline phosphatase to para-nitrophenol which inhibits the enhanced chemiluminescent reaction. The detection limit for the enzyme using the proenhancer and pro-anti-enhancer assays was 100 attomoles and 1 picomole, respectively. The proenhancer strategy was effective in assays for beta-D-galactosidase, beta-D-glucosidase and aryl sulfatase. A limited comparison of the proenhancer and a conventional colorimetric assay for an alkaline phosphatase label in an enzyme immunoassay for alpha-fetoprotein showed good agreement.

  8. Aphyllin, the first isoferulic acid glycoside and other phenolics from Tamarix aphylla flowers.

    PubMed

    Nawwar, M A M; Hussein, S A M; Ayoub, N A; Hofmann, K; Linscheid, M; Harms, M; Wende, K; Lindequist, U

    2009-05-01

    The first glycosylated isoferulic acid, isoferulic acid 3-O-beta-glucopyranoside, together with the new phenolics, tamarixetin 3,3'-di-sodium sulphate and dehydrodigallic acid dimetyl ester have been characterized from a flower extract of Tamarix aphylla. The structures were established on the basis of spectral data. The extract exhibited a distinct radical scavenging effect and to improve the viability of human keratinocytes (HaCaT cells). Also, the known isoferulic acid and ferulic acid which have been determined to be the major components of the investigated extract by HPLC/ESI mass spectrometric screening have been separated, characterized and evaluated as active antioxidants and as cell activity stimulating agents as well.

  9. AFRRI (Armed Forces Radiobiology Research Institute) reports, April-June 1986. Technical report

    SciTech Connect

    Not Available

    1986-01-01

    Contents include the following: disodium cryomoglycate, a mast-cell stabilizer, alters postradiation regional cerebral blood flow in primates; intracellular recordings from pineal cells in tissue culture: membrane properties and response to norepinephrine; gamma radiation affects active electrolyte transport by rabbit ileum: basal Na and Cl transport; histamine H2 receptors mediate morphine-induced locomotor hyperactivity of the C57BL/6J mouse; Interleukin 1 is a radioprotector; histamine decreased calcium-mediated potassium current in guinea pig hippocampal ca1 pyramidal cells; cytochemical study of developing neurotransmitter properties of dissociated sympathetic neurons grown in co-culture with dissociated pineal cells: angiotensin II-induced taste aversion learning in cats and rats and the role of the area postrema; effects of area postrema lesions on taste aversions produced by treatment with WU-2721 in the rat; and DOD nuclear mishaps.

  10. Isoelectric focusing in a silica nanofluidic channel: effects of electromigration and electroosmosis.

    PubMed

    Hsu, Wei-Lun; Inglis, David W; Startsev, Michael A; Goldys, Ewa M; Davidson, Malcolm R; Harvie, Dalton J E

    2014-09-02

    Isoelectric focusing of proteins in a silica nanofluidic channel filled with citric acid and disodium phosphate buffers is investigated via numerical simulation. Ions in the channel migrate in response to (i) the electric field acting on their charge and (ii) the bulk electroosmotic flow (which is directed toward the cathode). Proteins are focused near the low pH (anode) end when the electromigration effect is more significant and closer to the high pH (cathode) end when the electroosmotic effect dominates. We simulate the focusing behavior of Dylight labeled streptavidin (Dyl-Strep) proteins in the channel, using a relationship between the protein's charge and pH measured in a previous experiment. Protein focusing results compare well to previous experimental measurements. The effect of some key parameters, such as applied voltage, isoelectric point (pI), bulk pH, and bulk conductivity, on the protein trapping behavior in a nanofluidic channel is examined.

  11. Discrimination of Umami Tastants Using Floating Electrode-Based Bioelectronic Tongue Mimicking Insect Taste Systems.

    PubMed

    Lee, Minju; Jung, Je Won; Kim, Daesan; Ahn, Young-Joon; Hong, Seunghun; Kwon, Hyung Wook

    2015-12-22

    We report a floating electrode-based bioelectronic tongue mimicking insect taste systems for the detection and discrimination of umami substances. Here, carbon nanotube field-effect transistors with floating electrodes were hybridized with nanovesicles containing honeybee umami taste receptor, gustatory receptor 10 of Apis mellifera (AmGr10). This strategy enables us to discriminate between l-monosodium glutamate (MSG), best-known umami tastant, and non-umami substances with a high sensitivity and selectivity. It could also be utilized for the detection of MSG in liquid food such as chicken stock. Moreover, we demonstrated the synergism between MSG and disodium 5'-inosinate (IMP) for the umami taste using this platform. This floating electrode-based bioelectronic tongue mimicking insect taste systems can be a powerful platform for various applications such as food screening, and it also can provide valuable insights on insect taste systems.

  12. Polyacrolein microspheres as a new tool in cell biology.

    PubMed

    Margel, S; Beitler, U; Ofarim, M

    1982-08-01

    Polyacrolein (PA) microspheres in sizes ranging from 0.04 micron to 40 microns were synthesized. Magnetic and fluorescent PA microspheres were formed by carrying out the polymerization process in the presence of appropriate ferrofluidic or fluorochromic compounds, respectively. The microspheres carry reactive aldehyde groups, through which various ligands, containing primary amino groups, were covalently bound at physiological pH values. The potential use of these microspheres was demonstrated by the specific labelling of fresh human red blood cells (RBC) and by the separation of human RBC from turkey RBC by means of a magnetic field. PA microspheres were also bound covalently to the anti-allergic drug disodium chromoglycate (DSCG) and the conjugate was used for the labelling of rat basophilic leukaemia cells.

  13. [Study of simultaneous determination of residual veterinary drugs including tetracycline antibiotics in milk and dairy products].

    PubMed

    Yoshida, Emiko; Shibuya, Takahiro; Kurokawa, Chieko; Inoue, Yutaka; Yamamoto, Yoshihiko; Miyazaki, Motonobu

    2009-10-01

    It is considered to be difficult to detect tetracycline antibiotics in all-at-once simultaneous analysis with other drugs by liquid chromatography with tandem mass spectrometry, because tetracycline antibiotics chelate with bivalent metal ions such as calcium in samples. Therefore, we studied simultaneous determination of tetracycline antibiotics after removal of calcium with disodium ethylenediaminotetraacetate (EDTA-2Na). Tetracycline antibiotics could be assayed in all-at-once analysis by adding EDTA-2Na during the extraction procedure. It was possible to determine 65 veterinary drugs in milk, 70 in yogurt, 59 in whipped cream, 67 in cheese and 60 in ice cream. Recovery ranged from 70 to 120%, with a coefficient of variation of less than 25% and with a quantification limit of 0.01 microg/g (S/N>or=10).

  14. Chemical weathering of kimberlitic garnets: An experimental study (organic etching in ATP-Na2 salt)

    NASA Astrophysics Data System (ADS)

    Afanasiev, V. P.; Snegirev, O. V.; Kozmenko, O. A.; Pokhilenko, N. P.

    2014-12-01

    The morphology of garnets exposed to chemical weathering has been studied experimentally by etching in ATP disodium salt. After eighteen months, pyropes have developed etch patterns on grain surfaces identical to those produced by dissolution in their naturally occurring counterparts from in lateritic profiles. The mineral surface microtopography mainly corresponds to dislocation patterns, though positive elements of cuboid morphology are present as well. Similar corroded surfaces in pyropes have resulted from HF etching for 42 days: dislocation and cuboid dissolution, scratches, etch channels and grooves. Although the dissolution mechanisms are different, both reagents produce similar surface patterns, possibly, because dissolution localizes primarily at structure defects in minerals. However, HF providing much faster dissolution of pyrope is more preferable for the experimental use than ATP-Na2.

  15. Interaction between lyotropic chromonic liquid crystals and polymers

    NASA Astrophysics Data System (ADS)

    Yao, Xuxia; Park, Jung; Srinivasarao, Mohan

    2010-03-01

    Lyotropic chromonic liquid crystals (LCLCs) consist of various dyes, drugs, etc., so their importance is self-evident. The interaction of chromonic molecules and polymers is involved in their real applications, such as the dyeing process of fibers, textiles and food, and the functionalization of drugs in vivo. In our research, polymer dispersed LCLC droplets and polymer coated LCLC cells have been fabricated. Effect of interaction was observed by optical texture of LCLCs, as the different polymers induce different director configuration of LCLCs. A textile dye-Benzopurpurine 4B, food dye-Sunset Yellow FCF, and drug-Disodium Cromoglycate mixed with water soluble polymers, proteins and textile polymers have been all studied and compared.

  16. Beneficial effect of long term intravenous bisphosphonate treatment of osteogenesis imperfecta

    PubMed Central

    Astrom, E; Soderhall, S

    2002-01-01

    Aim: To find an effective symptomatic treatment for osteogenesis imperfecta (OI). Methods: In a prospective observational study disodium pamidronate (APD) was given as monthly intravenous infusions to 28 children and adolescents (aged 0.6–18 years) with severe OI or a milder form of the disease, but with spinal compression fractures. Results: During treatment for 2–9 years, dual energy x ray absorptiometry measurements of the total body and of the lumbar spine showed a gradual increase in bone density. All bone metabolism variables in serum (alkaline phosphatase, osteocalcin, procollagen 1 C-terminal peptide, collagen 1 teleopeptide) and urine (deoxypyridinoline) indicated that there was a decrease in bone turnover. All patients experienced beneficial effects and the younger patients reported a major improvement in wellbeing, pain, and mobility without significant side effects. Vertebral remodelling was also seen. Conclusions: APD seems to be an efficient symptomatic treatment for children and adolescents with OI. PMID:11970931

  17. Differential elution of sodium or potassium dihydrogen- and hydrogenphosphate ions from a sephadex G-15 column with sodium or potassium chloride solution.

    PubMed

    Okada, T K; Miyakoshi, M; Inoue, M; Nakabayashi, Y; Jisaki, F

    2001-04-20

    When a mixed solution of sodium or potassium dihydrogenphosphate and disodium or dipotassium hydrogenphosphate was eluted from a Sephadex G-15 column with either a sodium or potassium chloride solution, the elution profiles of ions showed that the hydrogenphosphate ion was eluted more rapidly than the dihydrogenphosphate ion. When the sample solutions containing potassium dihydrogenphosphate and/or dipotassium hydrogenphosphate, all of which were supplemented with phosphorus-32-labelled potassium dihydrogenphosphate, were eluted with sodium chloride solution, the elution profiles of radioactivity showed that the dihydrogenphosphate ion changed to hydrogenphosphate ion and vice versa, depending on the pH values of the sample solution and the availability of the cation of the eluent during elution for the phosphate ion to pair with.

  18. Stability of ranitidine in injectable solutions.

    PubMed

    Vehabovic, Midhat; Hadzovic, Sabira; Stambolic, Fatima; Hadzic, Amina; Vranjes, Elvedina; Haracic, Ediba

    2003-04-30

    Injectable solutions of ranitidine were prepared by dissolving ranitidine hydrochloride in water for injections. The following buffering system has been used: disodium phosphate (anhydrous), potassium dihydrogen phosphate, and phenol as a preservative. Inert gas (nitrogen) was used to displace oxygen from a solution and reduce the possibility of oxidative changes in the formulation. The solution was poured into 2-ml brown glass ampoules in asceptic condition. Ampoules samples have been stored at three different temperatures. They have been stored at 55 and 40 degrees C for 6 months, and at 25 degrees C for 12 months. TLC technique has been used for monitoring related substances, and HPLC technique for monitoring phenol and ranitidine content. It has been shown that only those samples that were stored at 25 degrees C were actually stable.

  19. Anti-allergic activities of a new benzopyranopyridine derivative Y-12,141 in rats.

    PubMed

    Goto, K; Terasawa, M; Maruyama, Y

    1979-01-01

    Passive cutaneous anaphylaxis (PCA) mediated in rats by IgE-like antibodies against egg albumin or the benzylpenicilloyl determinant was inhibited in a dose-dependent manner by intravenous treatment with Y-12,141; the ED50 was 0.09--0.2 mg/kg. The inhibitory effect of Y-12,141 ON PCA was about 5 times as potent as that of disodium cromoglycate (DSCG). Oral treatment with Y-12,141 resulted in the inhibition of PCA, showing an ED50 of 2.5 mg/kg. This action of Y-12,141 on PCA was considered to be due to the inhibition of the release of allergic mediatros from mast cells in a manner similar to DSCG. The results suggest that Y-12,141 may have an anti-allergic activity.

  20. Anti-anaphylactic activities of a new benzopyranopyridine derivative Y-12,141 in rats and guinea pigs.

    PubMed

    Goto, K; Terasawa, M; Kadobe, Y; Maruyama, Y

    1980-08-01

    The active anaphylactic bronchoconstriction of rats mediated by IgE-like antibody against DNP-Ascaris was inhibited by intravenous and intratracheal treatment with Y-12,141 in a dose-dependent manner. In both routes, the inhibitory effect of Y-12,141 on this response was more potent than that of disodium cromoglycate (DSCG). The oral administration of Y-12,141 also produced a similar inhibition of the response. The passive anaphylactic bronchoconstriction of guinea pigs mediated by IgG-like antibody against egg albumin was also prevented dose-dependently by treatment with Y-12,141 given intravenously, but not with DSCG. The present results suggest that Y-12,141 may be effective for the treatment of allergic bronchial asthma.

  1. A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease.

    PubMed

    Hori, Yukiko; Takeda, Shuko; Cho, Hansang; Wegmann, Susanne; Shoup, Timothy M; Takahashi, Kazue; Irimia, Daniel; Elmaleh, David R; Hyman, Bradley T; Hudry, Eloise

    2015-01-23

    Interfering with the assembly of Amyloid β (Aβ) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-Aβ-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of Aβ monomers into higher-order oligomers and fibrils in vitro without affecting Aβ production. In vivo, the levels of soluble Aβ are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble Aβ in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on Aβ economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease.

  2. Effects of Pamidronate on Dental Enamel Formation Assessed by Light Microscopy, Energy-Dispersive X-Ray Analysis, Scanning Electron Microscopy, and Microhardness Testing.

    PubMed

    Soares, Ana P; do Espírito Santo, Renan F; Line, Sérgio R P; Pinto, Maria das G F; Santos, Pablo de M; Toralles, Maria Betania P; do Espírito Santo, Alexandre R

    2016-06-01

    The aim of the present work was to investigate birefringence and morphology of the secretory-stage enamel organic extracellular matrix (EOECM), and structural and mechanical properties of mature enamel of upper incisors from adult rats that had been treated with pamidronate disodium (0.5 mg/kg/week for 56 days), using transmitted polarizing and bright-field light microscopies (TPLM and BFLM), energy-dispersive X-ray (EDX) analysis, scanning electron microscopy (SEM) and microhardness testing. BFLM showed no morphological changes of the EOECM in pamidronate and control groups, but TPLM revealed a statistically significant reduction in optical retardation values of birefringence brightness of pamidronate-treated rats when compared with control animals (p0.05). The present study indicates that pamidronate can affect birefringence of the secretory-stage EOECM, which does not seem to be associated with significant changes in morphological and/or mechanical properties of mature enamel.

  3. Three cases of lead toxicity associated with consumption of ayurvedic medicines.

    PubMed

    Raviraja, A; Vishal Babu, G N; Sehgal, Anusha; Saper, Robert B; Jayawardene, Innocent; Amarasiriwardena, Chitra J; Venkatesh, T

    2010-07-01

    Ayurveda is a traditional form of medicine used by majority of the Indians. Here we report three cases of lead toxicity, following intake of Ayurvedic medicines. Three patients presented with blood lead levels (BLLs) of 122.4, 115 and 42.8 μg/dl respectively at the time of hospitalization. The first case was chelated with D- penicillamine, the second with calcium disodium ethylene diamino tetra acetate (EDTA) and the third with environmental intervention and education. Associated Ayurvedic products were collected from patients and analyzed for metallic concentration. Cessation of Ayurvedic medication along with chelation, nutritional intervention and education, reduced the BLL to 27.4 μg/dl in the first case after 1 year, 21.1 μg/dl after 9 months in the second and 18.2 μg/dl after 6 months in the third case.

  4. The effects of EDTA and EGTA on renin secretion.

    PubMed Central

    Peart, W S; Quesada, T; Tenyi, I

    1977-01-01

    1 The effects of the disodium salt of ethylenediamine tetra-acetate (EDTA) and 1, 2, bis, 2 aminoethoxyethane-NNN'N'-tetra-acetic acid (EGTA) on renin secretion and vascular resistance were studied in the isolated perfused kidney of the rat. 2 Both substances produced a significant increase of renin release 3 In the absence of calcium and magnesium, EDTA still increased rein release and there was now a considerable increase of perfusion pressure. 4 The rise of pressure but not the rise of renin was inhibited by the removal of potassium from the perfusate when EDTA was administered in the absence of calcium. 5 Propranolol and phenoxybenzamine had no effect on the vasoconstrictor action of EDTA. 6 EGTA was less effective as a renin releaser than EDTA until magnesium was removed from the perfusate. Furter, it had only a small effect on perfusion pressure in contrast to EDTA. PMID:402166

  5. Effect of Sodium Carboxymethyl Celluloses on Water-catalyzed Self-degradation of 200-degree C-heated Alkali-Activated Cement

    SciTech Connect

    Sugama T.; Pyatina, T.

    2012-05-01

    We investigated the usefulness of sodium carboxymethyl celluloses (CMC) in promoting self-degradation of 200°C-heated sodium silicate-activated slag/Class C fly ash cementitious material after contact with water. CMC emitted two major volatile compounds, CO2 and acetic acid, creating a porous structure in cement. CMC also reacted with NaOH from sodium silicate to form three water-insensitive solid reaction products, disodium glycolate salt, sodium glucosidic salt, and sodium bicarbonate. Other water-sensitive solid reaction products, such as sodium polysilicate and sodium carbonate, were derived from hydrolysates of sodium silicate. Dissolution of these products upon contact with water generated heat that promoted cement’s self-degradation. Thus, CMC of high molecular weight rendered two important features to the water-catalyzed self-degradation of heated cement: One was the high heat energy generated in exothermic reactions in cement; the other was the introduction of extensive porosity into cement.

  6. Removable colored coatings based on calcium alginate hydrogels.

    PubMed

    Kobaslija, Muris; McQuade, D Tyler

    2006-08-01

    This article describes the creation of a nontoxic, biodegradable coating using calcium alginate and FD&C approved dyes. The coating is robust but is rapidly removed upon treatment with disodium ethylenediamine tetraacetate (EDTA). Dye leaching from calcium alginate films was studied, and it was determined that the efficiency of dye retention is proportional to the degree of cross-linking. Degradation rates were studied on calcium alginate beads serving as a model for a coating. We determined that degradation rates depend on the gel's cross-linking and on the amount of EDTA used. Bead size also influenced the degradation rates; smaller beads degraded faster than larger beads. We show that the coating can be used as an easily removable and environmentally friendly logotype on an artificial turf surface. Applications of these coatings can be extended to food, cosmetic, medicinal, and textile uses and to wherever nontoxic, easily removable colored coating is desired.

  7. Self-quenching of uranin: Instrument response function for color sensitive photo-detectors

    PubMed Central

    Luchowski, Rafal; Sabnis, Sushant; Szabelski, Mariusz; Sarkar, Pabak; Raut, Sangram; Gryczynski, Zygmunt; Borejdo, Julian; Bojarski, Piotr; Gryczynski, Ignacy

    2011-01-01

    Concentration is a key determining factor in the fluorescence properties of organic fluorophores. We studied self-quenching of disodium fluorescein (uranin) fluorescence in polyvinyl alcohol (PVA) thin films. The concentration dependent changes in brightness and anisotropy were followed by a lifetime decrease. We found that at a concentration of 0.54 M, the lifetime decreases to 7 ps. At a concentration of 0.18 M the lifetime was 10 ps with the relatively high quantum yield of 0.002. In these conditions the fluorescence intensity decay was homogeneous (well approximated by a single lifetime). We realized that such a sample was an ideal fluorescence lifetime standard for spectroscopy and microscopy, and therefore characterized instrument response functions for a time-domain technique. We show that self-quenched uranin enables measurements free of the color effect, making it a superior choice for a lifetime reference over scattered light. PMID:21331290

  8. Carboxylate-based receptors for the recognition of carbohydrates in organic and aqueous media.

    PubMed

    Mazik, Monika; Cavga, Hüseyin

    2006-04-14

    Acyclic receptors containing neutral and ionic hydrogen-bonding sites, such as amino-pyridine and carboxylate groups, were prepared and their binding properties toward neutral sugar molecules were studied. The binding studies with disodium and bis(tetramethylammonium) salts containing the dianion 11 have revealed that this type of receptor molecule is able to recognize the selected sugars in both organic and aqueous media. The carboxylate/pyridine-based receptor 11 exhibits in chloroform at least a 100-fold higher affinity for glucopyranosides than the previously described triarmed pyridine-based receptor 1, incorporating only neutral hydrogen-bonding sites. A substantial drop in the association constants is expectedly observed for an ester analogue of 11, compound 9. The dicarboxylate 11 is able to form complexes in water with methyl beta-D-glucopyranoside and D-cellobiose, with a preference for the disaccharide. The studies show the importance of charge-reinforced hydrogen bonds in the recognition of carbohydrates.

  9. Fall of zinc protoporphyrin levels in workers treated for chronic lead intoxication

    SciTech Connect

    Hryhorczuk, D.O.; Hogan, M.M.; Mallin, K.; Hessl, S.M.; Orris, P.

    1985-11-01

    A temporal fall of zinc protoporphyrin (ZPP) levels in whole blood was observed in 51 patients with occupational chronic lead intoxication who were removed from exposure, treated with intravenous calcium disodium edetate (EDTA), and followed for periods up to 2273 days. ZPP levels fell, with a mean half-life of 68 days, to a mean baseline level of 36 micrograms/dl of whole blood. The baseline ZPP level was positively associated with the length of exposure (p less than .01) and the blood lead half-life (p less than .001). The amount of EDTA received had no apparent effect on ZPP levels. These data suggest that the fall of ZPP levels is largely a function of red blood cell turnover. The baseline ZPP level appears to be a useful biologic index of the biologically active pool of lead for at least two years after removal from exposure.

  10. Influence of magnetic treatment of surfactant solutions on the properties of foams and on foam formation

    SciTech Connect

    Zal'tsman, M.D.; Dyusebaev, M.K.; Sulyaeva, N.G.

    1986-09-10

    One of the fields of application of surfactants is dust suppression by the foam method. Its effectiveness may be raised both by selection of suitable surfactants and by electrophysical methods of treatment of the surfactant solutions and of foam. The purpose of the present work was to study the influence of preliminary magnetic treatment of solutions of anionic and nonionic surfactants on the formation and properties of foam. The chosen surfactants were: the technical foaming agent PO-1 (disodium salts of alkyl-aromatic sulfonic acids based on kerosine), foaming agent PO-12, specially formulated for dust suppression (mixture of sodium primary alkylsulfates and alkylsulfonate with additions of glycerol and sodium hexametaphosphate), wetting agent OP-10 (monoalkylphenyl ether of polyethylene glycol based on polymer distillate), all made in the USSR, and Ditalon OTS (mixture of aliphatic alkyl sulfates), produced in East Germany.

  11. Effect of tartarate and citrate based food additives on the micellar properties of sodium dodecylsulfate for prospective use as food emulsifier.

    PubMed

    Banipal, Tarlok S; Kaur, Harjinder; Kaur, Amanpreet; Banipal, Parampaul K

    2016-01-01

    Citrate and tartarate based food preservatives can be used to enhance the emulsifying properties of sodium dodecylsulfate (SDS) based micellar system and thus making it appropriate for food applications. Exploration of interactions between the two species is the key constraint for execution of such ideas. In this work various micellar and thermodynamic parameters of SDS like critical micellar concentration (CMC), standard Gibbs free energy of micellization (ΔG(0)mic.) etc. have been calculated in different concentrations of disodium tartarate (DST) and trisodium citrate (TSC) in the temperature range (288.15-318.15)K from the conductivity and surface tension measurements. The parameters obtained from these studies reveal the competitive nature of both the additives with SDS for available positions at the air/water interface. TSC is found to be more effective additive in order to make SDS micellar system better for its potential applications as food emulsifier.

  12. Na2MoO2As2O7

    PubMed Central

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

    2012-01-01

    Disodium molybdenum dioxide diarsenate, Na2MoO2As2O7, has been synthesized by a solid-state reaction. The structure is built up from MoAs2O12 linear units sharing corners to form a three-dimensional framework containing tunnels running along the a-axis direction in which the Na+ cations are located. In this framework, the AsV atoms are tetra­hedrally coordinated and form an As2O7 group. The MoVI atom is displaced from the center of an octa­hedron of O atoms. Two Na+ cations are disordered about inversion centres. Structural relationships between different compounds: A 2MoO2As2O7 (A = K, Rb), AMOP2O7 (A = Na, K, Rb; M = Mo, Nb) and MoP2O7 are discussed. PMID:23468669

  13. Novel method for the preparation of core shell nanoparticles with movable Ag core and polystyrene loop shell

    NASA Astrophysics Data System (ADS)

    Liu, Wei-Jun; Zhang, Zhi-Cheng; He, Wei-Dong; Zheng, Cheng; Ge, Xue-Wu; Li, Jian; Liu, Hua-Rong; Jiang, Hao

    2006-04-01

    Core/shell nanoparticles with movable silver (Ag) core and polystyrene (PSt) shell (Ag@PSt nanoparticle) were successfully synthesized at room temperature and under ambient pressure via two steps: γ-irradiation and interfacial-initiated polymerization. Firstly, mono-dispersed Ag nanoparticles with diameters 20 nm were synthesized in inversed microemulsion by reducing silver nitrate under γ-irradiation. Then, Ag nanoparticles were coated with PSt via interfacial-initiated polymerization with cumene hydroperoxide/ferrous sulfate/disodium ethylenediaminetetraacetate/sodium formaldehyde sulfoxylate (CHPO-Fe 2+-EDTA-SFS) as the redox initiation pair. The resulted Ag@PSt nanoparticles were identified by transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray powder diffraction (XRD) and X-ray photoelectron spectroscopy (XPS).

  14. Effect of additives on the purification of urease

    NASA Astrophysics Data System (ADS)

    Yu, X.; Wang, J.; Ulrich, J.

    2015-12-01

    The effect of additives on the purification of proteins was investigated. The target protein studied here is the enzyme urease. Studies on the purification of urease from jack bean meal were carried out. 32% (v/v) acetone was utilized to extract urease from the jack bean meal. Further purification by crystallization with the addition of 2-mercaptoethanol and EDTA disodium salt dehydrate was carried out. It was found out that the presence of additives can affect the selectivity of the crystallization. Increases in both purity and yield of the urease after crystallization were observed in the presence of additives, which were proven using both SDS-PAGE and activity. Urease crystals with a yield of 69.9% and a purity of 85.1% were obtained in one crystallization step in the presence of additives. Furthermore, the effect of additives on the thermodynamics and kinetics of urease crystallization was studied.

  15. Polyhydroxylated sulfated steroids derived from 5α-cholestanes as antiviral agents against herpes simplex virus.

    PubMed

    Pujol, Carlos A; Sepúlveda, Claudia S; Richmond, Victoria; Maier, Marta S; Damonte, Elsa B

    2016-07-01

    Twelve polyhydroxylated sulfated steroids synthesized from a 5α-cholestane skeleton with different substitutions in C-2, C-3 and C-6 were evaluated for cytotoxicity and antiviral activity against herpes simplex virus (HSV) by a virus plaque reduction assay. Four compounds elicited a selective inhibitory effect against HSV. The disodium salt of 2β,3α-dihydroxy-6E-hydroximine-5α-cholestane-2,3-disulfate, named compound 7, was the most effective inhibitor of HSV-1, HSV-2 and pseudorabies virus (PrV) strains, including acyclovir-resistant variants, in human and monkey cell lines. Preliminary mechanistic studies demonstrated that compound 7 did not affect the initial steps of virus entry but inhibited a subsequent event in the infection process of HSV.

  16. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    PubMed Central

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai-Zhuang; Lin, Zijing; Zhu, Zi-Zhong; Ho, Kai-Ming

    2015-01-01

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. These structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs. PMID:26497381

  17. Efficient Conjugated Polymer-Methyl Viologen Electron Transfer System for Controlled Photo-Driven Hydrogen Evolution.

    PubMed

    Lu, Huan; Hu, Rong; Bai, Haotian; Chen, Hui; Lv, Fengting; Liu, Libing; Wang, Shu; Tian, He

    2017-03-13

    Photo-driven hydrogen production has been a good strategy in solar energy utilization. In this work, we use a water-soluble negatively charged polythiophene derivative as photosensitizer to produce hydrogen from aqueous solution containing methyl viologen (MV2+), ethylenediaminetetraacetic acid disodium salt (EDTA) and a colloidal platinum catalyst upon exposure to Xenon lamp (> 420 nm) or natural sunlight. The supramolecular assembly and dis-assembly processes of MV2+ and cucurbit[8]uril (CB[8]) was further used to reversibly "turn-on" and "turn-off" hydrogen generation of the polymer system. This research offers a proof-of-concept to control hydrogen generation in demand, which is an advantage for hydrogen utilization and storage.

  18. Full scale field demonstration on the use of hydrogen peroxide for in situ bioremediation of an aviation gasoline-contaminated aquifer (Chapter 16). Book chapter

    SciTech Connect

    Wilson, J.T.; Armstrong, J.M.; Rafai, H.S.

    1994-01-01

    The U.S. Environmental Protection Agency (EPA) and the U.S. Coast Guard conducted a joint full-scale evaluation of in situ biological treatement of Petroleum Hydrocarbons (PHCs) following spillage of aviation gasoline at a Coast Guard Air Station in Traverse City, MI. At the Coast Guard site, soil core samples were collected and analyzed to quantify aviation gasoline contamination in the aquifer. Hydraulic modeling was used to design an infiltration system that flooded all of the fuel-contaminated subsurface soil. The spill area was pretreated with groundwater, which was amended with 380 mg/L ammonium chloride, 190 mg/L disodium phosphate, and 190 mg/L potassium phosphate. The groundwater concentration of benzene in the most contaminated depth interval at the site was reduced to <1 microgram/L. Remaining alkylbenzenes were also reduced to below federal drinking water standards. (Copyright (c) 1994 by Lewis Publishers).

  19. Preparation and Mechanism of Controllable Micropores on Bioceramic TiO2 Coatings by Plasma Electrolytic Oxidation

    NASA Astrophysics Data System (ADS)

    Wang, Hong-Yuan; Zhu, Rui-Fu; Lu, Yu-Peng; Xiao, Gui-Yong; Ma, Jie; Yuan, Y. F.

    2013-09-01

    Porous titania coatings with Ca and P elements were synthesized by plasma electrolytic oxidation (PEO). The treatment was carried out in an electrolyte containing calcium acetate monohydrate and disodium phosphate dodecahydrate (Ca/P = 5), and 4-20 μm micropores were prepared on the coatings by applied pulse frequencies of 200-1000 Hz. The surface structure, chemical composition of the TiO2 coatings, and time-dependent variation of electric currents were studied. The result revealed that the coating micropores, which could be controlled in size, increased with higher frequency, and the coatings mainly consisted of anatase and rutile phases with varying fractions. Based on our experiment, the formation mechanism of micropores and phases of the PEO coatings was further discussed in details.

  20. Effect of coating material on uptake of indocyanine green-loaded nanocapsules by HeLa cervical cancer cells

    NASA Astrophysics Data System (ADS)

    Jung, Bongsu; Lomeli, Eulieses; Anvari, Bahman

    2010-02-01

    Fluorescent molecular probes offer a potential for early cancer detection. Indocyanine green (ICG) is an FDAapproved near-infrared (NIR) fluorescent dye used in ophthalmic angiography and assessment of cardiac and hepatic functions. However, clinical applications of ICG remain very limited due to its rapid clearance from vascular circulation, unstable optical properties, non-specific interactions with plasma proteins, and inability for localized targeting. To overcome these limitations, we have encapsulated ICG within nanoconstructs composed of poly(allylamine) hydrochloride and disodium hydrogen phosphate salt. To understand the effects of coating materials on the cellular uptake of the nanocapsules, we have measured the uptake of ICG-loaded nanocapsules (ICG-NCs) with various coating materials by HeLa cancerous cervical epithelial cells in-vitro. Results of this study provide important information for the choice of appropriate coating materials that will result in maximal uptake of ICG-NCs in optical and phototherapy of cancerous tissue.

  1. Assessment of boric acid and borax using the IEHR evaluative process for assessing human developmental and reproductive toxicity of agents

    SciTech Connect

    Moore, J.A.

    1995-03-01

    This document presents an evaluation of the reproductive and developmental effects of boric acid, H3BO3 (CAS Registry No. 10043-35-3) and disodium tetraborate decahydrate or borax, Na2B4O2O(CAS Registry No. 1303-96-4). The element, boron, does not exist naturally. In dilute aqueous solution and at physiological pH (7.4), the predominant species in undissociated boric acid (greater than 98%), irrespective of whether the initial material was boric acid of borax. Therefore, it is both useful and correct to compare exposures and dosages to boric acid and borax in terms of `boron equivalents`, since both materials form equivalent species in dilute aqueous solution with similar systemic effects. In order to be clear in this document, the term `boron` will refer to `boron equivalents` or percent boron in boric acid and borax.

  2. Effects of Himatanthus lancifolius on human leukocyte chemotaxis and their adhesion to integrins.

    PubMed

    Nardin, Jeanine Marie; de Souza, Wesley Maurício; Lopes, Juliano Ferreira; Florão, Angela; de Moraes Santos, Cid Aimbiré; Weffort-Santos, Almeriane Maria

    2008-08-01

    The aim of this work was to investigate the anti-inflammatory activities of the uleine-rich fraction extracted from the barks of Himatanthus lancifolius (Muell. Arg.) Woodson (Apocynaceae). To achieve this, we focused on its in vitro effects on some steps of the inflammatory response using peripheral human leukocytes. The results presented herein show that the uleine-rich fraction significantly inhibits the migration of casein-induced granulocytes and their adhesion to fibronectin and vitronectin, along with mononuclear cells, by down-regulating the expression of alpha 4beta1 and alpha5beta1 integrins. The data suggest that H. LANCIFOLIUS has the potential of interferring with leukocyte trafficking through its uleine-rich fraction, emphasizing its usefulness in inflammatory conditions. DEXA:dexamethasone disodium phosphate FN:fibronectin PMN:polymorphonuclear URF:uleine-rich fraction VN:vitronectin.

  3. [Structural analyses of unknown red dyes detected in dried strawberry].

    PubMed

    Shindo, Tetsuya; Sadamasu, Yuki; Suzuki, Keiko; Tanaka, Yasukazu; Togawa, Akiko; Nakajima, Junichi; Nakazato, Mitsuo; Uematsu, Yoko

    2012-01-01

    We examined two unknown red dyes (designated as red dyes "A" and "B") from a dried strawberry package with a label that indicated the presence of food red No. 40 (R40). Red dye "A" was identified as trisodium 3-hydroxy-4-[(2'-methoxy-5'-methyl-4'-sulfonatophenyl)azo]-2,7-naphthalenedisulfonate (CSA-R) by HPLC, UV-VIS spectra and MS spectra. This compound is one of the four reported subsidiary colors of R40. Detailed analyses of red dye "B" by MS and NMR demonstrated that its structure was disodium 3-hydroxy-4-[(2'-methoxy-5'-methyl-4'-sulfonatophenyl)azo]-2-naphthalenesulfonate. Red dye "B" is a structural isomer of R40, that has not been reported previously. Our results suggest that the two minor red dyes were subsidiary colors contained in R40, which had been added to the dried strawberries.

  4. Safety Assessment of Alkyl PEG Sulfosuccinates as Used in Cosmetics.

    PubMed

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

    2015-09-01

    The Cosmetic Ingredient Review (CIR) Expert Panel (Panel) reviewed the safety of alkyl polyethylene glycol (PEG) sulfosuccinates, which function in cosmetics mostly as surfactants/cleansing agents. Although these ingredients may cause ocular and skin irritation, dermal penetration is unlikely because of the substantial polarity and molecular size of these ingredients. The Panel considered the negative oral carcinogenicity and reproductive and developmental toxicity data on chemically related laureths (PEG lauryl ethers) and negative repeated dose toxicity and skin sensitization data on disodium laureth sulfosuccinate supported the safety of these alkyl PEG sulfosuccinates in cosmetic products, but. The CIR Expert Panel concluded that the alkyl PEG sulfosuccinates are safe in the present practices of use and concentration when formulated to be nonirritating.

  5. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    SciTech Connect

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai -Zhuang; Lin, Zijing; Zhu, Zi -Zhong; Ho, Kai -Ming

    2015-10-26

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. In addition, these structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.

  6. Optical principle of pH measurement for detection of auxin flow through cellular membrane

    NASA Astrophysics Data System (ADS)

    Podrazky, Ondrej; Mrazek, Jan; Seidl, Miroslav; Kasik, Ivan; Tobiska, Petr; Matejec, Vlastimil; Martan, Tomas; Aubrecht, Jan

    2007-05-01

    The paper shows an approach to the determination of pH changes of solutions with a fine spatial resolution by means of fiber-optic tapers and fluorescence detection. This approach can be adopted for the determination of auxin flow through celluar membranes. Spectral absorption and fluorescence of pH transducers, namely of fluorescein, carboxyfluorescein, 6,8-dihydroxy-1,3-pyrenedisulfonic acid disodium salt and 2',7'-bis(2-carbonylethyl)-5(6)-carboxyfluorescein, were tested. The approach, based on the determination of a shift of the maxima of their fluorescence peaks, was employed for processing the measured fluorescence data in bulk solutions. Suitable tapered fiber probes were prepared and in vitro demonstrated for pH monitoring in a pH range from 6 to 7.

  7. AgNa2Mo3O9AsO4

    PubMed Central

    Hamza, Hamadi; Zid, Mohamed Faouzi; Driss, Ahmed

    2011-01-01

    The title compound, silver disodium trimolybdenum(VI) nonaoxide arsenate, AgNa2Mo3O9AsO4, was prepared by a solid-state reaction at 808 K. The structure consists of an infinite (Mo3AsO13)n ribbon, parallel to the c axis, composed of AsO4 tetra­hedra and MoO6 octa­hedra sharing edges and corners. The Na and Ag ions partially occupy several independent close positions, with various occupancies, in the inter-ribbon space delimited by the one-dimensional framework. The composition was refined to Ag1.06(1)Na1.94(1)Mo3O9AsO4. PMID:22219728

  8. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme.

    PubMed

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; Nguyen, Manh Cuong; Wang, Cai-Zhuang; Lin, Zijing; Zhu, Zi-Zhong; Ho, Kai-Ming

    2015-10-26

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. These structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been much less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.

  9. Exploration of tetrahedral structures in silicate cathodes using a motif-network scheme

    DOE PAGES

    Zhao, Xin; Wu, Shunqing; Lv, Xiaobao; ...

    2015-10-26

    Using a motif-network search scheme, we studied the tetrahedral structures of the dilithium/disodium transition metal orthosilicates A2MSiO4 with A = Li or Na and M = Mn, Fe or Co. In addition to finding all previously reported structures, we discovered many other different tetrahedral-network-based crystal structures which are highly degenerate in energy. In addition, these structures can be classified into structures with 1D, 2D and 3D M-Si-O frameworks. A clear trend of the structural preference in different systems was revealed and possible indicators that affect the structure stabilities were introduced. For the case of Na systems which have been muchmore » less investigated in the literature relative to the Li systems, we predicted their ground state structures and found evidence for the existence of new structural motifs.« less

  10. Studies on the reverse osmosis treatment of uranyl nitrate solution

    SciTech Connect

    Prabhakar, S.; Panicker, S.T.; Misra, B.M.; Ramani, P.S. )

    1992-03-01

    The aqueous effluent generated in uranium processing, particularly in the nuclear fuel fabrication step, contains mainly uranium nitrate. This requires treatment before discharge into the environment to meet stringent standards. This paper presents the performance of cellulose acetate membranes with regard to rejection of uranium under reverse osmotic conditions for feed concentrations up to 200 mg/l of uranium, which corresponds to the levels normally prevalent in the effluents. The use of additives like the disodium salt of ethylenediaminetetraacetic acid and sodium sulfate for the improvement of reverse osmosis performance of the above membranes was also investigated. In the light of the experimental results, the suitability of reverse osmosis for the decontamination of uranium effluents is discussed.

  11. Study of the Agglomeration of 5 to 25nm Gold Nanoparticles as a Function of Viscosity and Ionic Concentration

    NASA Astrophysics Data System (ADS)

    Stefankiewicz, Adam; Dobbins, Tabbetha

    2013-03-01

    Gold nanoparticles (AuNPs) attached to carcinoma cells and treated with light irradiation are able to convert the light into heat energy, thus killing those cells. In order to get the particles to the affected area, they may be entered into the circulatory system where the environment is highly viscous and comprised of high salt concentrations. This study examines the aggregation behavior of gold nanoparticles under those conditions. Surface charge creates coulombic repulsion between particles. Likewise, highly viscous solutions will prevent aggregation by limiting the rate of transport of gold through the solution. This study examines the aggregation behavior of gold nanopartilces as a function of viscosity (varied using polyethylene glycol). The study also examines the role of excess ions in the solution (varied using 5-Bromo-4-chloro-3-indolyl phosphate disodium salt). The aggregation phenomena was explored using dynamic light scattering for particle size analysis. Early results are presented here.

  12. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    NASA Astrophysics Data System (ADS)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  13. A Novel High-Throughput Approach to Measure Hydroxyl Radicals Induced by Airborne Particulate Matter

    PubMed Central

    Son, Yeongkwon; Mishin, Vladimir; Welsh, William; Lu, Shou-En; Laskin, Jeffrey D.; Kipen, Howard; Meng, Qingyu

    2015-01-01

    Oxidative stress is one of the key mechanisms linking ambient particulate matter (PM) exposure with various adverse health effects. The oxidative potential of PM has been used to characterize the ability of PM induced oxidative stress. Hydroxyl radical (•OH) is the most destructive radical produced by PM. However, there is currently no high-throughput approach which can rapidly measure PM-induced •OH for a large number of samples with an automated system. This study evaluated four existing molecular probes (disodium terephthalate, 3′-p-(aminophenyl)fluorescein, coumarin-3-carboxylic acid, and sodium benzoate) for their applicability to measure •OH induced by PM in a high-throughput cell-free system using fluorescence techniques, based on both our experiments and on an assessment of the physicochemical properties of the probes reported in the literature. Disodium terephthalate (TPT) was the most applicable molecular probe to measure •OH induced by PM, due to its high solubility, high stability of the corresponding fluorescent product (i.e., 2-hydroxyterephthalic acid), high yield compared with the other molecular probes, and stable fluorescence intensity in a wide range of pH environments. TPT was applied in a high-throughput format to measure PM (NIST 1648a)-induced •OH, in phosphate buffered saline. The formed fluorescent product was measured at designated time points up to 2 h. The fluorescent product of TPT had a detection limit of 17.59 nM. The soluble fraction of PM contributed approximately 76.9% of the •OH induced by total PM, and the soluble metal ions of PM contributed 57.4% of the overall •OH formation. This study provides a promising cost-effective high-throughput method to measure •OH induced by PM on a routine basis. PMID:26516887

  14. Osmotolerance in Escherichia coli is improved by activation of copper efflux genes or supplementation with sulfur containing amino acids.

    PubMed

    Xiao, Mengyong; Zhu, Xinna; Fan, Feiyu; Xu, Hongtao; Tang, Jinlei; Qin, Ying; Ma, Yanhe; Zhang, Xueli

    2017-01-23

    Improvement in the osmotolerance of Escherichia coli is essential for the production of high titers of various bioproducts. In this work, a cusS mutation identified in the previously constructed high succinate-producing E. coli strain HX024 was investigated for its effect on osmotolerance. CusS is part of the two-component system CusSR that protects cell from Ag(I) and Cu(I) toxicity. Changing cusS from strain HX024 back to its original sequence led to a 24% decrease in cell mass and succinate titer under osmotic stress (12% glucose). When cultivated with a high initial glucose concentration (12%), introduction of the cusS mutation into parental strain Suc-T110 led to a 21% increase in cell mass and 40% increase in succinate titer. When the medium was supplemented with 30 g/L disodium succinate, the cusS mutation led to a 120% increase in cell mass and 492% increase in succinate titer. Introducing the cusS mutation into the wild-type strain ATCC 8739 led to increases in cell mass of 87% with 20% glucose and 36% using 30 g/L disodium succinate. The cusS mutation increased expression of cusCFBA, and gene expression levels were found to be positively related to osmotolerance abilities. Because high osmotic stress has been associated with deleterious accumulation of Cu(I) in the periplasm, activation of CusCFBA might alleviate this effect by transporting Cu(I) out of the cells. This hypothesis was confirmed by supplementing sulfur-containing amino acids that could chelate Cu(I). Adding methionine or cysteine to the medium increased the osmotolerance of E. coli under anaerobic conditions.

  15. Organic anodes and sulfur/selenium cathodes for advanced Li and Na batteries

    NASA Astrophysics Data System (ADS)

    Luo, Chao

    To address energy crisis and environmental pollution induced by fossil fuels, there is an urgent demand to develop sustainable, renewable, environmental benign, low cost and high capacity energy storage devices to power electric vehicles and enhance clean energy approaches such as solar energy, wind energy and hydroenergy. However, the commercial Li-ion batteries cannot satisfy the critical requirements for next generation rechargeable batteries. The commercial electrode materials (graphite anode and LiCoO 2 cathode) are unsustainable, unrenewable and environmental harmful. Organic materials derived from biomasses are promising candidates for next generation rechargeable battery anodes due to their sustainability, renewability, environmental benignity and low cost. Driven by the high potential of organic materials for next generation batteries, I initiated a new research direction on exploring advanced organic compounds for Li-ion and Na-ion battery anodes. In my work, I employed croconic acid disodium salt and 2,5-Dihydroxy-1,4-benzoquinone disodium salt as models to investigate the effects of size and carbon coating on electrochemical performance for Li-ion and Na-ion batteries. The results demonstrate that the minimization of organic particle size into nano-scale and wrapping organic materials with graphene oxide can remarkably enhance the rate capability and cycling stability of organic anodes in both Li-ion and Na-ion batteries. To match with organic anodes, high capacity sulfur and selenium cathodes were also investigated. However, sulfur and selenium cathodes suffer from low electrical conductivity and shuttle reaction, which result in capacity fading and poor lifetime. To circumvent the drawbacks of sulfur and selenium, carbon matrixes such as mesoporous carbon, carbonized polyacrylonitrile and carbonized perylene-3, 4, 9, 10-tetracarboxylic dianhydride are employed to encapsulate sulfur, selenium and selenium sulfide. The resulting composites exhibit

  16. Rheological properties of reversible thermo-setting in situ gelling solutions with the methylcellulose-polyethylene glycol-citric acid ternary system (2): Effects of various water-soluble polymers and salts on the gelling temperature.

    PubMed

    Shimokawa, Ken-ichi; Saegusa, Katsuhiko; Ishii, Fumiyoshi

    2009-11-01

    The influences of various salts and water-soluble polymers on the phase transition temperature of thermo-setting gels prepared by combining methylcellulose (MC)-sodium citrate (SC)-polyethylene glycol (PEG) at appropriate ratios (the MC-SC-PEG system) were investigated. Concerning cations, comparison of the phase transition temperature between SC and tripotassium citrate (PC) showed a rapid increase in the viscosity of SC between 20 degrees C and 25 degrees C and an increase in the viscosity of PC between 30 degrees C and 35 degrees C. Concerning the valency of anions, comparisons among SC, disodium tartrate dihydrate (ST), disodium maleate hemihydrates (SM), and sodium sulfate (SS) showed a rapid increase in the viscosity of trivalent SC between 20 degrees C and 25 degrees C and changes in the viscosity of the three bivalent sodium salts (ST, SM, and SS) at > or =30 degrees C. Thus the phase transition temperature decreased with an increase in the valency of anions. Subsequently, the influences of various water-soluble polymers on the gelling temperature were compared. Using polyvinylpyrrolidone (PVP) instead of PEG, the gelling temperature decreased with an increase in the PVP concentration even without the addition of SC. Unlike PVP, the addition of xanthan gum as a viscosity-increasing polysaccharide did not reduce the gelling temperature irrespective of its concentration. Temperature-associated changes in viscosity were observed at a fixed SC concentration with changes in the concentration of PVP or PEG. The gel phase transition temperature increased from 46 degrees C to 50 degrees C in gels not containing PVP or PEG. The viscosity did not differ between the addition of PVP or PEG at a low concentration and its absence. However, the viscosity clearly changed after the addition of each agent at a high concentration.

  17. Chelant-assisted phytoextraction and accumulation of Zn by Zea mays.

    PubMed

    Gheju, M; Stelescu, I

    2013-10-15

    Zea mays plants were exposed to soils with concentrations of Zn ranging from 64 to 1800 mg kg(-1) dw, and the efficiency of three selected chelating agents (trisodium citrate (CI), disodium oxalate (OX) and disodium dihydrogen ethylene-diamine-tetraacetate (EDTA)) in enhancing metal phytoextraction was compared. Zn concentration in plant tissues increased in conjunction with the metal concentration of the soil. EDTA was found to be the most efficient chelating amendment, increasing concentrations of Zn in shoots from 88 mg kg(-1) dw, at 64 mg kg(-1) dw soil, to 8026 mg kg(-1) dw at 1800 mg kg(-1) dw soil. The overall orders of BCFs and TFs which resulted from this study are: EDTA > H2O > OX > CI, and EDTANa2 > OX > CI > H2O, respectively. The more effective uptake of Zn by plants for the control treatment (distilled water only) than for CI and OX was attributed to the neutral or slightly alkaline pH of the two chelant irrigation solutions. Instead, EDTA had a favorable effect on Zn uptake from soil due to its additive chelating and acidifying properties. Among the three chelants, only EDTA significantly increased the Zn phytoextraction potential of Z. mays, while CI and OX induced a low metal uptake from soil by plants. Although Z. mays has a lower Zn accumulation capacity than the hyperaccumulator Thlaspi caerulescens, it could be considered as a potential phytoremediator of soils with elevated Zn concentrations, especially when metal pollution extends to depths greater than 20 cm.

  18. Microbicide excipients can greatly increase susceptibility to genital herpes transmission in the mouse

    PubMed Central

    2010-01-01

    Background Several active ingredients proposed as vaginal microbicides have been shown paradoxically to increase susceptibility to infection in mouse genital herpes (HSV-2) vaginal susceptibility models and in clinical trials. In addition, "inactive ingredients" (or excipients) used in topical products to formulate and deliver the active ingredient might also cause epithelial toxicities that increase viral susceptibility. However, excipients have not previously been tested in susceptibility models. Methods Excipients commonly used in topical products were formulated in a non-toxic vehicle (the "HEC universal placebo"), or other formulations as specified. Twelve hours after exposure to the excipient or a control treatment, mice were challenged with a vaginal dose of HSV-2, and three days later were assessed for infection by vaginal lavage culture to assess susceptibility. Results The following excipients markedly increased susceptibility to HSV-2 after a single exposure: 5% glycerol monolaurate (GML) formulated in K-Y® Warming Jelly, 5% GML as a colloidal suspension in phosphate buffered saline, K-Y Warming Jelly alone, and both of its humectant/solvent ingredients (neat propylene glycol and neat PEG-8). For excipients formulated in the HEC vehicle, 30% glycerin significantly increased susceptibility, and a trend toward increased HSV-2 susceptibility was observed after 10% glycerin, and 0.1% disodium EDTA, but not after 0.0186% disodium EDTA. The following excipients did not increase susceptibility: 10% propylene glycol, 0.18%, methylparaben plus 0.02% propylparaben, and 1% benzyl alcohol. Conclusions As reported with other surfactants, the surfactant/emulsifier GML markedly increased susceptibility to HSV-2. Glycerin at 30% significantly increased susceptibility, and, undiluted propylene glycol and PEG-8 greatly increased susceptibility. PMID:21087496

  19. Effect of glycine on pH changes and protein stability during freeze-thawing in phosphate buffer systems.

    PubMed

    Pikal-Cleland, Katherine A; Cleland, Jeffrey L; Anchordoquy, Thomas J; Carpenter, John F

    2002-09-01

    Previous studies have established that the selective precipitation of a less soluble buffer component during freezing can induce a significant pH shift in the freeze concentrate. During freezing of sodium phosphate solutions, crystallization of the disodium salt can produce a pH decrease as great as 3 pH units which can dramatically affect protein stability. The objective of our study was to determine how the presence of glycine (0-500 mM), a commonly used bulking agent in pharmaceutical protein formulations, affects the pH changes normally observed during freezing in sodium phosphate buffer solutions and to determine whether these pH changes contribute to instability of model proteins in glycine/phosphate formulations. During freezing in sodium phosphate buffers, the presence of glycine significantly influenced the pH. Glycine at the lower concentrations (< or = 50 mM) suppressed the pH decrease normally observed during freezing in 10 and 100 mM sodium phosphate buffer, possibly by reducing the nucleation rate of salt and thereby decreasing the extent of buffer salt crystallization. The presence of glycine at higher concentration (> 100 mM) in the sodium phosphate buffer resulted in a more complete crystallization of the disodium salt as indicated by the frozen pH values closer to the equilibrium value (pH 3.6). Although high concentrations of glycine can facilitate more buffer salt crystallization and these pH shifts may prove to be potentially damaging to the protein, glycine, in its amorphous state, can also act to stabilize a protein via the preferential exclusion mechanism.

  20. Why the NIH Trial to Assess Chelation Therapy (TACT) Should Be Abandoned

    PubMed Central

    Atwood, Kimball C.; Woeckner, Elizabeth; Baratz, Robert S.; Sampson, Wallace I.

    2008-01-01

    The National Institutes of Health (NIH) Trial to Assess Chelation Therapy (TACT) was begun in 2003 and is expected to be completed in 2009. It is a trial of office-based, intravenous disodium ethylene-diamine-tetra-acetic acid (Na2EDTA) as a treatment for coronary artery disease (CAD). A few case series in the 1950s and early 1960s had found Na2EDTA to be ineffective for CAD or peripheral vascular disease (PVD). Nevertheless, a few hundred physicians, almost all of whom advocate other dubious treatments, continued to peddle chelation as an office treatment. They claim that chelation dramatically improves symptoms and prolongs life in 80% to 90% of patients. In response, academics performed 4 controlled trials during the 1990s. None favored chelation, but chelationists repudiated those findings. We have investigated the method and the trial. We present our findings in 4 parts: history, origin and nature of the TACT, state of the evidence, and risks. We present evidence that chelationists and their organization, the American College for Advancement in Medicine, used political connections to pressure the NIH to fund the TACT. The TACT protocols justified the trial by misrepresenting case series and by ignoring evidence of risks. The trial employs nearly 100 unfit co-investigators. It conflates disodium EDTA and another, somewhat safer drug. It lacks precautions necessary to minimize risks. The consent form reflects those shortcomings and fails to disclose apparent proprietary interests. The trial's outcome will be unreliable and almost certainly equivocal, thus defeating its stated purpose. We conclude that the TACT is unethical, dangerous, pointless, and wasteful. It should be abandoned. PMID:18596934

  1. Human-parathormone assay for use in dogs: validation, sample handling studies, and parathyroid function testing.

    PubMed

    Torrance, A G; Nachreiner, R

    1989-07-01

    Ten commercially available parathormone (PTH) assays were competitively validated, using dilutional parallelism, intra-assay and interassay coefficients of variation, and sensitivity and measured responses of 2 dogs to calcium and EDTA infusions. A 2-site immunoradiometric assay for intact human-PTH was superior to the others for estimating canine-PTH, met the criteria for validity, and was further investigated. A series of sample-handling studies was performed. Serum and plasma samples stored at 24 C lost 15% (n = 5; P less than 0.05) of PTH between 2 and 24 hours. This did not occur at 6 C. The mean PTH concentration of sera from blood samples clotted at 24 C was 6% (P less than 0.05) higher than equivalent EDTA samples. Serum samples stored at 6 and 37 C deteriorated 35% and 100% (n = 5; P less than 0.05), respectively, after 1 week, whereas samples stored at -20 and -70 C for 4 weeks did not deteriorate. There was no significant deterioration of PTH in samples frozen (-40 C) and thawed up to 7 times (n = 5). Parathyroid function testing was investigated by use of 2-hour infusions of disodium EDTA (25 mg/kg/h), 10-minute infusions of calcium gluconate (3 mg of elemental calcium/kg/10 min), and physiologic saline controls (n = 8). Renal function was monitored before and after EDTA infusion by exogenous creatinine clearance. Infusion of disodium EDTA increased mean PTH concentration from 67 (time 0) to 317 and 235 pg/ml at 90 and 180 minutes, respectively (P less than 0.001). Infusion of calcium gluconate decreased mean PTH concentration from 84 (time 0) to 14 and 12 pg/ml at 15 and 60 minutes, respectively (P less than 0.005). There were no observable side effects of the infusions in normal conscious dogs and no differences in exogenous creatinine clearance after EDTA infusion.

  2. Self-assembled organic nanowires for high power density lithium ion batteries.

    PubMed

    Luo, Chao; Huang, Ruiming; Kevorkyants, Ruslan; Pavanello, Michele; He, Huixin; Wang, Chunsheng

    2014-03-12

    The electroactive organic materials are promising alternatives to inorganic electrode materials for the new generation of green Li-ion batteries due to their sustainability, environmental benignity, and low cost. Croconic acid disodium salt (CADS) was used as Li-ion battery electrode, and CADS organic wires with different diameters were fabricated through a facile synthetic route using antisolvent crystallization method to overcome the challenges of low electronic conductivity of CADS and lithiation induced strain. The CADS nanowire exhibits much better electrochemical performance than its crystal bulk material and microwire counterpart. CADS nanowire with a diameter of 150 nm delivers a reversible capability of 177 mAh g(-1) at a current density of 0.2 C and retains capacity of 170 mAh g(-1) after 110 charge/discharge cycles. The nanowire structure also remarkably enhances the kinetics of croconic acid disodium salt. The CADS nanowire retains 50% of the 0.1 C capacity even when the current density increases to 6 C. In contrast, the crystal bulk and microwire material completely lose their capacities when the current density merely increases to 2 C. Such a high rate performance of CADS nanowire is attributed to its short ion diffusion pathway and large surface area, which enable fast ion and electron transport in the electrode. The theoretical calculation suggests that lithiation of CADS experiences an ion exchange process. The sodium ions in CADS will be gradually replaced by lithium ions during the lithiation and delithiation of CADS electrode, which is confirmed by inductively coupled plasma test.

  3. Intercellular Ca(2+) wave propagation in human retinal pigment epithelium cells induced by mechanical stimulation.

    PubMed

    Abu Khamidakh, A E; Juuti-Uusitalo, K; Larsson, K; Skottman, H; Hyttinen, J

    2013-03-01

    Ca(2+) signaling is vitally important in cellular physiological processes and various drugs also affect Ca(2+) signaling. Thus, knowledge of Ca(2+) dynamics is important toward understanding cell biology, as well as the development of drug-testing assays. ARPE-19 cells are widely used for modeling human retinal pigment epithelium functions and drug-testing, but intercellular communication has not been assessed in these cells. In this study, we investigated intercellular Ca(2+) communication induced by mechanical stimulation in ARPE-19 cells. An intercellular Ca(2+) wave was induced in ARPE-19 monolayer by point mechanical stimulation of a single cell. Dynamic changes of intracellular Ca(2+) concentration ([Ca(2+)](i)) in the monolayer were tracked with fluorescence microscopy imaging using Ca(2+)-sensitive fluorescent dye fura-2 in presence and absence of extracellular Ca(2+), after depletion of intracellular Ca(2+) stores with thapsigargin, and after application of gap junction blocker α-glycyrrhetinic acid and P2-receptor blocker suramin. Normalized fluorescence values, reflecting amplitude of [Ca(2+)](i) increase, and percentage of responsive cells were calculated to quantitatively characterize Ca(2+) wave propagation. Mechanical stimulation of a single cell within a confluent monolayer of ARPE-19 cells initiated an increase in [Ca(2+)](i), which propagated to neighboring cells in a wave-like manner. Ca(2+) wave propagated to up to 14 cell tiers in control conditions. The absence of extracellular Ca(2+) reduced [Ca(2+)](i) increase in the cells close to the site of mechanical stimulation, whereas the depletion of intracellular Ca(2+) stores with thapsigargin blocked the wave spreading to distant cells. The gap junction blocker α-glycyrrhetinic acid reduced [Ca(2+)](i) increase in the cell tiers close to the site of mechanical stimulation, indicating involvement of gap junctions in Ca(2+) wave propagation. The P2-receptor blocker suramin reduced the percentage

  4. Contribution of K(+) channels to endothelium-derived hypolarization-induced renal vasodilation in rats in vivo and in vitro.

    PubMed

    Rasmussen, Kasper Moller Boje; Braunstein, Thomas Hartig; Salomonsson, Max; Brasen, Jens Christian; Sorensen, Charlotte Mehlin

    2016-07-01

    We investigated the mechanisms behind the endothelial-derived hyperpolarization (EDH)-induced renal vasodilation in vivo and in vitro in rats. We assessed the role of Ca(2+)-activated K(+) channels and whether K(+) released from the endothelial cells activates inward rectifier K(+) (Kir) channels and/or the Na(+)/K(+)-ATPase. Also, involvement of renal myoendothelial gap junctions was evaluated in vitro. Isometric tension in rat renal interlobar arteries was measured using a wire myograph. Renal blood flow was measured in isoflurane anesthetized rats. The EDH response was defined as the ACh-induced vasodilation assessed after inhibition of nitric oxide synthase and cyclooxygenase using L-NAME and indomethacin, respectively. After inhibition of small conductance Ca(2+)-activated K(+) channels (SKCa) and intermediate conductance Ca(2+)-activated K(+) channels (IKCa) (by apamin and TRAM-34, respectively), the EDH response in vitro was strongly attenuated whereas the EDH response in vivo was not significantly reduced. Inhibition of Kir channels and Na(+)/K(+)-ATPases (by ouabain and Ba(2+), respectively) significantly attenuated renal vasorelaxation in vitro but did not affect the response in vivo. Inhibition of gap junctions in vitro using carbenoxolone or 18α-glycyrrhetinic acid significantly reduced the endothelial-derived hyperpolarization-induced vasorelaxation. We conclude that SKCa and IKCa channels are important for EDH-induced renal vasorelaxation in vitro. Activation of Kir channels and Na(+)/K(+)-ATPases plays a significant role in the renal vascular EDH response in vitro but not in vivo. The renal EDH response in vivo is complex and may consist of several overlapping mechanisms some of which remain obscure.

  5. An endothelium-derived hyperpolarizing factor distinct from NO and prostacyclin is a major endothelium-dependent vasodilator in resistance vessels of wild-type and endothelial NO synthase knockout mice

    PubMed Central

    Brandes, Ralf P.; Schmitz-Winnenthal, Friedrich-Hubertus; Félétou, Michel; Gödecke, Axel; Huang, Paul L.; Vanhoutte, Paul M.; Fleming, Ingrid; Busse, Rudi

    2000-01-01

    In addition to nitric oxide (NO) and prostacyclin (PGI2), the endothelium generates the endothelium-derived hyperpolarizing factor (EDHF). We set out to determine whether an EDHF-like response can be detected in wild-type (WT) and endothelial NO synthase knockout mice (eNOS −/−) mice. Vasodilator responses to endothelium-dependent agonists were determined in vivo and in vitro. In vivo, bradykinin induced a pronounced, dose-dependent decrease in mean arterial pressure (MAP) which did not differ between WT and eNOS −/− mice and was unaffected by treatment with Nω-nitro-l-arginine methyl ester and diclofenac. In the saline-perfused hindlimb of WT and eNOS −/− mice, marked Nω-nitro-l-arginine (l-NA, 300 μmol/liter)- and diclofenac-insensitive vasodilations in response to both bradykinin and acetylcholine (ACh) were observed, which were more pronounced than the agonist-induced vasodilation in the hindlimb of WT in the absence of l-NA. This endothelium-dependent, NO/PGI2-independent vasodilatation was sensitive to KCl (40 mM) and to the combination of apamin and charybdotoxin. Gap junction inhibitors (18α-glycyrrhetinic acid, octanol, heptanol) and CB-1 cannabinoid-receptor agonists (Δ9-tetrahydrocannabinol, HU210) impaired EDHF-mediated vasodilation, whereas inhibition of cytochrome P450 enzymes, soluble guanylyl cyclase, or adenosine receptors had no effect on EDHF-mediated responses. These results demonstrate that in murine resistance vessels the predominant agonist-induced endothelium-dependent vasodilation in vivo and in vitro is not mediated by NO, PGI2, or a cytochrome P450 metabolite, but by an EDHF-like principle that requires functional gap junctions. PMID:10944233

  6. Glycyrrhizin Protects against Acetaminophen-Induced Acute Liver Injury via Alleviating Tumor Necrosis Factor α–Mediated Apoptosis

    PubMed Central

    Yan, Tingting; Wang, Hong; Zhao, Min; Yagai, Tomoki; Chai, Yingying; Krausz, Kristopher W.; Xie, Cen; Cheng, Xuefang; Zhang, Jun; Che, Yuan; Li, Feiyan; Wu, Yuzheng; Brocker, Chad N.; Gonzalez, Frank J.

    2016-01-01

    Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in Western countries. Glycyrrhizin (GL), a potent hepatoprotective constituent extracted from the traditional Chinese medicine liquorice, has potential clinical use in treating APAP-induced liver failure. The present study determined the hepatoprotective effects and underlying mechanisms of action of GL and its active metabolite glycyrrhetinic acid (GA). Various administration routes and pharmacokinetics–pharmacodynamics analyses were used to differentiate the effects of GL and GA on APAP toxicity in mice. Mice deficient in cytochrome P450 2E1 enzyme (CYP2E1) or receptor interacting protein 3 (RIPK3) and their relative wild-type littermates were subjected to histologic and biochemical analyses to determine the potential mechanisms. Hepatocyte death mediated by tumor necrosis factor α (TNFα)/caspase was analyzed by use of human liver-derived LO2 cells. The pharmacokinetics–pharmacodynamics analysis using various administration routes revealed that GL but not GA potently attenuated APAP-induced liver injury. The protective effect of GL was found only with intraperitoneal and intravenous administration and not with gastric administration. CYP2E1-mediated metabolic activation and RIPK3-mediated necroptosis were unrelated to GL’s protective effect. However, GL inhibited hepatocyte apoptosis via interference with TNFα-induced apoptotic hepatocyte death. These results demonstrate that GL rapidly attenuates APAP-induced liver injury by directly inhibiting TNFα-induced hepatocyte apoptosis. The protective effect against APAP-induced liver toxicity by GL in mice suggests the therapeutic potential of GL for the treatment of APAP overdose. PMID:26965985

  7. An automated method of on-line extraction coupled with flow injection and capillary electrophoresis for phytochemical analysis.

    PubMed

    Chen, Hongli; Ding, Xiuping; Wang, Min; Chen, Xingguo

    2010-11-01

    In this study, an automated system for phytochemical analysis was successfully fabricated for the first time in our laboratory. The system included on-line decocting, filtering, cooling, sample introducing, separation, and detection, which greatly simplified the sample preparation and shortened the analysis time. Samples from the decoction extract were drawn every 5 min through an on-line filter and a condenser pipe to the sample loop from which 20-μL samples were injected into the running buffer and transported into a split-flow interface coupling the flow injection and capillary electrophoresis systems. The separation of glycyrrhetinic acid (GTA) and glycyrrhizic acid (GA) took less than 5 min by using a 10 mM borate buffer (adjusted pH to 8.8) and +10 kV voltage. Calibration curves showed good linearity with correlation coefficients (R) more than 0.9991. The intra-day repeatabilities (n = 5, expressed as relative standard deviation) of the proposed system, obtained using GTA and GA standards, were 1.1% and 0.8% for migration time and 0.7% and 0.9% for peak area, respectively. The mean recoveries of GTA and GA in the off-line extract of Glycyrrhiza uralensis Fisch root were better than 99.0%. The limits of detection (signal-to-noise ratio = 3) of the proposed method were 6.2 μg/mL and 6.9 μg/mL for GTA and GA, respectively. The dynamic changes of GTA and GA on the decoction time were obtained during the on-line decoction process of Glycyrrhiza uralensis Fisch root.

  8. Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation.

    PubMed

    Yamada, Aya; Futagi, Masaharu; Fukumoto, Emiko; Saito, Kan; Yoshizaki, Keigo; Ishikawa, Masaki; Arakaki, Makiko; Hino, Ryoko; Sugawara, Yu; Ishikawa, Momoko; Naruse, Masahiro; Miyazaki, Kanako; Nakamura, Takashi; Fukumoto, Satoshi

    2016-01-08

    Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43(-/-) salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43(-/-) samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43(-/-) phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis.

  9. Down-regulation of 11β-hydroxysteroid dehydrogenase type 2 by bortezomib sensitizes Jurkat leukemia T cells against glucocorticoid-induced apoptosis.

    PubMed

    Tao, Yi; Gao, Lu; Wu, Xiaosong; Wang, Hongmei; Yang, Guang; Zhan, Fenghuang; Shi, Jumei

    2013-01-01

    11β-Hydroxysteroid dehydrogenases type 2 (11β-HSD2), a key regulator for pre-receptor metabolism of glucocorticoids (GCs) by converting active GC, cortisol, to inactive cortisone, has been shown to be present in a variety of tumors. But its expression and roles have rarely been discussed in hematological malignancies. Proteasome inhibitor bortezomib has been shown to not only possess antitumor effects but also potentiate the activity of other chemotherapeutics. In this study, we demonstrated that 11β-HSD2 was highly expressed in two GC-resistant T-cell leukemic cell lines Jurkat and Molt4. In contrast, no 11β-HSD2 expression was found in two GC-sensitive non-hodgkin lymphoma cell lines Daudi and Raji as well as normal peripheral blood T cells. Inhibition of 11β-HSD2 by 11β-HSD inhibitor 18β-glycyrrhetinic acid or 11β-HSD2 shRNA significantly increased cortisol-induced apoptosis in Jurkat cells. Additionally, pretreatment of Jurkat cells with low-dose bortezomib resulted in increased cellular sensitivity to GC as shown by elevated induction of apoptosis, more cells arrested at G1 stage and up-regulation of GC-induced leucine zipper which is an important mediator of GC action. Furthermore, we clarified that bortezomib could dose-dependently inhibit 11β-HSD2 messenger RNA and protein levels as well as activity (cortisol-cortisone conversion) through p38 mitogen-activated protein kinase signaling pathway. Therefore, we suggest 11β-HSD2 is, at least partially if not all, responsible for impaired GC suppression in Jurkat cells and also indicate a novel mechanism by which proteasome inhibitor bortezomib may influence GC action.

  10. Temporal sequence of activation of cells involved in purinergic neurotransmission in the colon

    PubMed Central

    Baker, Salah A; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M

    2015-01-01

    Interstitial cells, known as platelet derived growth factor receptor α (PDGFRα+) cells, are closely associated with varicosities of enteric motor neurons and suggested to mediate purinergic hyperpolarization responses in smooth muscles of the gastrointestinal tract (GI), but this concept has not been demonstrated directly in intact muscles. We used confocal microscopy to monitor Ca2+ transients in neurons and post-junctional cells of the murine colon evoked by exogenous purines or electrical field stimulation (EFS) of enteric neurons. EFS (1–20 Hz) caused Ca2+ transients in enteric motor nerve processes and then in PDGFRα+ cells shortly after the onset of stimulation (latency from EFS was 280 ms at 10 Hz). Responses in smooth muscle cells (SMCs) were typically a small decrease in Ca2+ fluorescence just after the initiation of Ca2+ transients in PDGFRα+ cells. Upon cessation of EFS, several fast Ca2+ transients were noted in SMCs (rebound excitation). Strong correlation was noted in the temporal characteristics of Ca2+ transients evoked in PDGFRα+ cells by EFS and inhibitory junction potentials (IJPs) recorded with intracellular microelectrodes. Ca2+ transients and IJPs elicited by EFS were blocked by MRS-2500, a P2Y1 antagonist, and absent in P2ry1(−/−) mice. PDGFRα+ cells expressed gap junction genes, and gap junction uncouplers, 18β-glycyrrhetinic acid (18β-GA) and octanol blocked Ca2+ transients in SMCs but not in neurons or PDGFRα+ cells. IJPs recorded from SMCs were also blocked. These findings demonstrate direct innervation of PDGFRα+ cells by motor neurons. PDGFRα+ cells are primary targets for purinergic neurotransmitter(s) in enteric inhibitory neurotransmission. Hyperpolarization responses are conducted to SMCs via gap junctions. PMID:25627983

  11. Mutual enhancement of differentiation of osteoblasts and osteocytes occurs through direct cell-cell contact.

    PubMed

    Fujita, Koji; Xing, Qian; Khosla, Sundeep; Monroe, David G

    2014-11-01

    There is increasing evidence that osteocytes regulate multiple aspects of bone remodeling through bi-directional communication with osteoblasts. This is potentially mediated through cell-cell contact via osteocytic dendritic processes, through the activity of secreted factors, or both. To test whether cell-cell contact affects gene expression patterns in osteoblasts and osteocytes, we used a co-culture system where calvarial osteoblasts and IDG-SW3 osteocytes were allowed to touch through a porous membrane, while still being physically separated to allow for phenotypic characterization. Osteoblast/osteocyte cell-contact resulted in up-regulation of osteoblast differentiation genes in the osteoblasts, when compared to wells where no cell contact was allowed. Examination of osteocyte gene expression when in direct contact with osteoblasts also revealed increased expression of osteocyte-specific genes. These data suggest that physical contact mutually enhances both the osteoblastic and osteocytic character of each respective cell type. Interestingly, Gja1 (a gap junction protein) was increased in the osteoblasts only when in direct contact with the osteocytes, suggesting that Gja1 may mediate some of the effects of direct cell contact. To test this hypothesis, we treated the direct contact system with the gap junction inhibitor 18-alpha-glycyrrhetinic acid and found that Bglap expression was significantly inhibited. This suggests that osteocytes may regulate late osteoblast differentiation at least in part through Gja1. Identification of the specific factors involved in the enhancement of differentiation of both osteoblasts and osteocytes when in direct contact will uncover new biology concerning how these bone cells communicate.

  12. Electrical coupling synchronises spinal motoneuron activity during swimming in hatchling Xenopus tadpoles.

    PubMed

    Zhang, Hong-Yan; Li, Wen-Chang; Heitler, William J; Sillar, Keith T

    2009-09-15

    The role of electrical coupling between neurons in the swimming rhythm generator of Xenopus embryos has been studied using pharmacological blockade of gap junctions. A conspicuous effect of 18beta-glycyrrhetinic acid (18beta-GA) and carbenoxolone, which have been shown to block electrical coupling in this preparation, was to increase the duration of ventral root bursts throughout the spinal cord during swimming. The left-right coordination, the swimming frequency and the duration of swimming episodes were not affected by concentrations of 18beta-GA which significantly increased burst durations. However, the longitudinal coupling was affected such that 18beta-GA led to a significant correlation between rostrocaudal delays and cycle periods, which is usually only present in older larval animals. Patch clamp recordings from spinal motoneurons tested whether gap junction blockers affect the spike timing and/or firing pattern of motoneurons during fictive swimming. In the presence of 18beta-GA motoneurons continued to fire a single, but broader action potential in each cycle of swimming, and the timing of their spikes relative to the ventral root burst became more variable. 18beta-GA had no detectable effect on the resting membrane potential of motoneurons, but led to a significant increase in input resistance, consistent with the block of gap junctions. This effect did not result in increased firing during swimming, despite the fact that multiple spikes can occur in response to current injection. Applications of 18beta-GA at larval stage 42 had no discernible effect on locomotion. The results, which suggest that electrical coupling primarily functions to synchronize activity in synergistic motoneurons during embryo swimming, are discussed in the context of motor system development.

  13. Controllable targeted system based on pH-dependent thermo-responsive nanoparticles.

    PubMed

    Yang, Chengling; Guo, Hua; Hu, Zhenpeng; Tian, Zhiqing; Wu, Yukun; Wang, Wei; Yuan, Zhi

    2015-11-01

    In this study, a pH-dependent thermo-responsive polymer (poly (N-isopropyl acrylamide-co-methacrylic acid-co-ethyl methacrylate, P(NIPAAm-co-MAA-co-EMA)), which was used as a masking functional module was designed and prepared. Its LCST was pH-dependent, leading to a sensitive isothermal phase transition between the blood and the extracellular environment of solid tumours. This masking polymer had a LCST of 36.4 °C at pH 6.5, and remained hydrophilic at pH 7.4 even when the temperature was increased to 50 °C. The liver-targeted nanoparticles (NPs) were then obtained by co-grafting the masking functional module and the targeting ligands glycyrrhetinic acid (GA) onto the gold nanoparticles (Au NPs). Their surface properties and targeting ability could be switched based on the expanding or shrinking behaviour of the polymers. The shielding/deshielding effect of GA was confirmed by the bovine serum albumin adsorption and cellular uptake. The results indicated that GA could be shielded by the hydrophilic P(NIPAAm-co-MAA-co-EMA) in the normal physiological environment (pH 7.4, 37 °C) and deshielded in the tumour microenvironment of pH 6.5, 40 °C, leading to an increase in cellular uptake as high as 2.3-fold compared with that observed at pH 7.4, 37 °C. More importantly, the ultrasensitive phase transition of the polymer was reversible, which means that the targeting ability of the deshielded Au NPs could be reshielded if they come back to the blood circulation.

  14. Multiple Psychopharmacological Effects of the Traditional Japanese Kampo Medicine Yokukansan, and the Brain Regions it Affects

    PubMed Central

    Mizoguchi, Kazushige; Ikarashi, Yasushi

    2017-01-01

    Yokukansan (YKS), a traditional Japanese Kampo medicine, has indications for use in night crying and irritability in children, as well as neurosis and insomnia. It is currently also used for the remedy of the behavioral and psychological symptoms of dementia (BPSD), such as aggressiveness, agitation, and hallucinations. In parallel with clinical evidence, a significant amount of fundamental researches have been undertaken to clarify the neuropsychopharmacological efficacies of YKS, with approximately 70 articles, including our own, being published to date. Recently, we reviewed the neuropharmacological mechanisms of YKS, including its effects on glutamatergic, serotonergic, and dopaminergic neurotransmission, and pharmacokinetics of the ingredients responsible for the effects. This review is aimed to integrate the information regarding the psychopharmacological effects of YKS with the brain regions known to be affected, to facilitate our understanding of the clinical efficacy of YKS. In this review, we first show that YKS has several effects that act to improve symptoms that are similar to BPSDs, like aggressiveness, hallucinations, anxiety, and sleep disturbance, as well as symptoms like tardive dyskinesia and cognitive deficits. We next provide the evidence showing that YKS can interact with various brain regions, including the cerebral cortex, hippocampus, striatum, and spinal cord, dysfunctions of which are related to psychiatric symptoms, cognitive deficits, abnormal behaviors, and dysesthesia. In addition, the major active ingredients of YKS, geissoschizine methyl ether and 18β-glycyrrhetinic acid, are shown to predominantly bind to the frontal cortex and hippocampus, respectively. Our findings suggest that YKS has multiple psychopharmacological effects, and that these are probably mediated by interactions among several brain regions. In this review, we summarize the available information about the valuable effects of a multicomponent medicine YKS on complex

  15. Morphological and physiological evidence for interstitial cell of Cajal-like cells in the guinea pig gallbladder.

    PubMed

    Lavoie, Brigitte; Balemba, Onesmo B; Nelson, Mark T; Ward, Sean M; Mawe, Gary M

    2007-03-01

    Gallbladder smooth muscle (GBSM) exhibits spontaneous rhythmic electrical activity, but the origin and propagation of this activity are not understood. We used morphological and physiological approaches to determine whether interstitial cells of Cajal (ICC) are present in the guinea pig extrahepatic biliary tree. Light microscopic studies involving Kit tyrosine kinase immunohistochemistry and laser confocal imaging of Ca(2+) transients revealed ICC-like cells in the gallbladder. One type of ICC-like cell had elongated cell bodies with one or two primary processes and was observed mainly along GBSM bundles and nerve fibres. The other type comprised multipolar cells that were located at the origin and intersection of muscle bundles. Electron microscopy revealed ICC-like cells that were rich in mitochondria, caveolae and smooth endoplasmic reticulum and formed close appositions between themselves and with GBSM cells. Rhythmic Ca(2+) flashes, which represent Ca(2+) influx during action potentials, were synchronized in any given GBSM bundle and associated ICC-like cells. Gap junction uncouplers (1-octanol, carbenoxolone, 18beta-glycyrrhetinic acid and connexin mimetic peptide) eliminated or greatly reduced Ca(2+) flashes in GBSM, but they persisted in ICC-like cells, whereas the Kit tyrosine kinase inhibitor, imanitib mesylate, eliminated or reduced action potentials and Ca(2+) flashes in both cell types, as well as associated tissue contractions. This study provides morphological and physiological evidence for the existence of ICC-like cells in the gallbladder and presents data supporting electrical coupling between ICC-like and GBSM cells. The results support a role for ICC-like cells in the generation and propagation of spontaneous rhythmicity, and hence, the excitability of gallbladder.

  16. In situ imaging of the autonomous intracellular Ca(2+) oscillations of osteoblasts and osteocytes in bone.

    PubMed

    Ishihara, Yoshihito; Sugawara, Yasuyo; Kamioka, Hiroshi; Kawanabe, Noriaki; Kurosaka, Hiroshi; Naruse, Keiji; Yamashiro, Takashi

    2012-04-01

    Bone cells form a complex three-dimensional network consisting of osteoblasts and osteocytes embedded in a mineralized extracellular matrix. Ca(2+) acts as a ubiquitous secondary messenger in various physiological cellular processes and transduces numerous signals to the cell interior and between cells. However, the intracellular Ca(2+) dynamics of bone cells have not been evaluated in living bone. In the present study, we developed a novel ex-vivo live Ca(2+) imaging system that allows the dynamic intracellular Ca(2+) concentration ([Ca(2+)](i)) responses of intact chick calvaria explants to be observed without damaging the bone network. Our live imaging analysis revealed for the first time that both osteoblasts and osteocytes display repetitive and autonomic [Ca(2+)](i) oscillations ex vivo. Thapsigargin, an inhibitor of the endoplasmic reticulum that induces the emptying of intracellular Ca(2+) stores, abolished these [Ca(2+)](i) responses in both osteoblasts and osteocytes, indicating that Ca(2+) release from intracellular stores plays a key role in the [Ca(2+)](i) oscillations of these bone cells in intact bone explants. Another possible [Ca(2+)](i) transient system to be considered is gap junctional communication through which Ca(2+) and other messenger molecules move, at least in part, across cell-cell junctions; therefore, we also investigated the role of gap junctions in the maintenance of the autonomic [Ca(2+)](i) oscillations observed in the intact bone. Treatment with three distinct gap junction inhibitors, 18α-glycyrrhetinic acid, oleamide, and octanol, significantly reduced the proportion of responsive osteocytes, indicating that gap junctions are important for the maintenance of [Ca(2+)](i) oscillations in osteocytes, but less in osteoblasts. Taken together, we found that the bone cells in intact bone explants showed autonomous [Ca(2+)](i) oscillations that required the release of intracellular Ca(2+) stores. In addition, osteocytes specifically

  17. Connexins form functional hemichannels in porcine ciliary epithelium.

    PubMed

    Shahidullah, Mohammad; Delamere, Nicholas A

    2014-01-01

    The expression of connexins in the ciliary epithelium is consistent with gap junctions between the pigmented (PE) and nonpigmented ciliary epithelium (NPE) that form when connexon hemichannels from adjacent cells pair to form a channel. Here we present evidence that suggests undocked connexons may form functional hemichannels that permit exchange of substances between NPE and the aqueous humor. Intact porcine eyes were perfused via the ciliary artery and propidium iodide (PI) (MW 668) was added to the aqueous humor compartment as a tracer. After calcium-free solution containing PI was introduced into the aqueous humor compartment for 30 min, fluorescence microscopy revealed PI in the NPE cell layer. PI entry into the NPE was inhibited by calcium and by the connexin antagonist 18α-glycyrrhetinic acid (18-AGA). Studies also were carried out with cultured porcine NPE. Under normal conditions, little PI entered the cultured cells but calcium-free medium stimulated PI accumulation and the entry was inhibited by 18-AGA. In cells loaded with calcein (MW 622), calcium-free solution stimulated calcein exit. 18-AGA partially suppressed calcein exit in calcium-free medium. Connexin 43 and connexin 50 proteins were detected by western blot analysis in both native and cultured NPE. In the intact eye, immunolocalization studies revealed connexin 50 at the basolateral, aqueous humor-facing, margin of the NPE. In contrast, connexin 43 was observed at the junction of the PE and NPE layer and on the basolateral membrane of PE. The results point to functional hemichannels at the NPE basolateral surface. It is feasible that hemichannels might contribute to the transfer of substances between the ciliary epithelium cytoplasm and aqueous humor.

  18. Pharmacological blockade of gap junctions induces repetitive surging of extracellular potassium within the locust CNS.

    PubMed

    Spong, Kristin E; Robertson, R Meldrum

    2013-10-01

    The maintenance of cellular ion homeostasis is crucial for optimal neural function and thus it is of great importance to understand its regulation. Glial cells are extensively coupled by gap junctions forming a network that is suggested to serve as a spatial buffer for potassium (K(+)) ions. We have investigated the role of glial spatial buffering in the regulation of extracellular K(+) concentration ([K(+)]o) within the locust metathoracic ganglion by pharmacologically inhibiting gap junctions. Using K(+)-sensitive microelectrodes, we measured [K(+)]o near the ventilatory neuropile while simultaneously recording the ventilatory rhythm as a model of neural circuit function. We found that blockade of gap junctions with either carbenoxolone (CBX), 18β-glycyrrhetinic acid (18β-GA) or meclofenamic acid (MFA) reliably induced repetitive [K(+)]o surges and caused a progressive impairment in the ability to maintain baseline [K(+)]o levels throughout the treatment period. We also show that a low dose of CBX that did not induce surging activity increased the vulnerability of locust neural tissue to spreading depression (SD) induced by Na(+)/K(+)-ATPase inhibition with ouabain. CBX pre-treatment increased the number of SD events induced by ouabain and hindered the recovery of [K(+)]o back to baseline levels between events. Our results suggest that glial spatial buffering through gap junctions plays an essential role in the regulation of [K(+)]o under normal conditions and also contributes to a component of [K(+)]o clearance following physiologically elevated levels of [K(+)]o.

  19. Role of gap junctions and protein kinase A during the development of oocyte maturational competence in Ayu (Plecoglossus altivelis)

    USGS Publications Warehouse

    Yamamoto, Y.; Yoshizaki, G.; Takeuchi, T.; Soyano, K.; Patino, R.

    2008-01-01

    Meiotic resumption in teleost oocytes is induced by a maturation-inducing hormone (MIH). The sensitivity of oocytes to MIH, also known as oocyte maturational competence (OMC), is induced by LH via mechanisms that are not fully understood. A previous study of Ayu (Plecoglossus altivelis) showed the presence of functional heterologous gap junctions (GJs) between oocytes and their surrounding granulosa cells. The objectives of this study were to determine the role of ovarian GJs and of protein kinase A (PKA) during the acquisition of OMC. We examined the effects of the specific GJ inhibitor carbenoxolone (CBX) and 18??-glycyrrhetinic acid (??-GA) on the LH-(hCG)-dependent acquisition of OMC and on MIH-(17,20??-dihydroxy-4-pregnen-3-one)-dependent meiotic resumption; measured the cAMP content of ovarian follicles during the hCG-dependent acquisition of OMC; and determined the effects of PK activators and inhibitors on hCG-dependent OMC. Production of follicular cAMP increased during the hCG-dependent acquisition of OMC. Both GJ inhibitors and the PKA inhibitor H8-dihydrochloride, but not the PKC inhibitor GF109203X, suppressed the hCG-dependent acquisition of OMC in a dose-dependent manner. The PKA activator forskolin induced OMC with a similar potency to hCG. Unlike previous observations with teleosts where disruption of heterologous GJ either blocks or stimulates meiotic resumption, treatment with GJ inhibitors did not affect MIH-dependent meiotic resumption in maturationally competent follicles of Ayu. These observations suggest that ovarian GJs are essential for LH-dependent acquisition of OMC but not for MIH-dependent meiotic resumption, and that the stimulation of OMC by LH is mediated by cAMP-dependent PKA. They are also consistent with the view that a precise balance between GJ-mediated signals (positive or negative) and oocyte maturational readiness is required for hormonally regulated meiotic resumption. ?? 2007 Elsevier Inc. All rights reserved.

  20. Blockage of androgen and administration of estrogen induce transdifferentiation of testis into ovary.

    PubMed

    Shi, Hongjuan; Gao, Tian; Liu, Zhilong; Sun, Lina; Jiang, Xiaolong; Chen, Lili; Wang, Deshou

    2017-04-01

    Induction of sex reversal of XY fish has been restricted to the sex undifferentiated period. In the present study, differentiated XY tilapia were treated with trilostane (TR), metopirone (MN) and glycyrrhetinic acid (GA) (inhibitor of 3β-HSD, Cyp11b2 and 11β-HSD, respectively) alone or in combination with 17β-estradiol (E2) from 30 to 90 dah (days after hatching). At 180 dah, E2 alone resulted in 8.3%, and TR, MN and GA alone resulted in no secondary sex reversal (SSR), whereas TR + E2, MN + E2 and GA + E2 resulted in 88.3, 60.0 and 46.7% of SSR, respectively. This sex reversal could be rescued by simultaneous administration of 11-ketotestosterone (11-KT). Compared with the control XY fish, decreased serum 11-KT and increased E2 level were detected in SSR fish. Immunohistochemistry analyses revealed that Cyp19a1a, Cyp11b2 and Dmrt1 were expressed in the gonads of GA + E2, MN + E2 and TR + E2 SSR XY fish at 90 dah, but only Cyp19a1a was expressed at 180 dah. When the treatment was applied from 60 to 120 dah, TR + E2 resulted in 3.3% of SSR, MN + E2 and GA + E2 resulted in no SSR. These results demonstrated that once 11-KT was synthesized, it could antagonize E2-induced male-to-female SSR, which could be abolished by simultaneous treatment with the inhibitor of steroidogenic enzymes. The upper the enzyme was located in the steroidogenic pathway, the higher SSR rate was achieved when it was inhibited as some of the precursors, such as androstenedione, testosterone and 5α-dihydrotestosterone, could act as androgens. These results highlight the key role of androgen in male sex maintenance.

  1. An overview on antidiabetic medicinal plants having insulin mimetic property.

    PubMed

    Patel, D K; Prasad, S K; Kumar, R; Hemalatha, S

    2012-04-01

    Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles.

  2. Mechanisms contributing to cluster formation in the inferior olivary nucleus in brainstem slices from postnatal mice.

    PubMed

    Kølvraa, Mathias; Müller, Felix C; Jahnsen, Henrik; Rekling, Jens C

    2014-01-01

    The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5-P15.5) spontaneously generates clusters of neurons with synchronous calcium transients, and intracellular recordings from IO neurons suggest that electrical coupling between neighbouring IO neurons may serve as a synchronizing mechanism. Here, we studied the cluster-forming mechanism and find that clusters overlap extensively with an overlap distribution that resembles the distribution for a random overlap model. The average somatodendritic field size of single curly IO neurons was ∼6400 μm(2), which is slightly smaller than the average IO cluster size. Eighty-seven neurons with overlapping dendrites were estimated to be contained in the principal olive mean cluster size, and about six non-overlapping curly IO neurons could be contained within the largest clusters. Clusters could also be induced by iontophoresis with glutamate. Induced clusters were inhibited by tetrodotoxin, carbenoxelone and 18β-glycyrrhetinic acid, suggesting that sodium action potentials and electrical coupling are involved in glutamate-induced cluster formation, which could also be induced by activation of N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Spikelets and a small transient depolarizing response were observed during glutamate-induced cluster formation. Calcium transients spread with decreasing velocity during cluster formation, and somatic action potentials and cluster formation are accompanied by large dendritic calcium transients. In conclusion, cluster formation depends on gap junctions, sodium action potentials and spontaneous clusters occur randomly throughout the IO. The relative slow signal spread during cluster formation, combined with a strong dendritic influx of calcium, may signify that active dendritic properties contribute to cluster formation.

  3. An overview on antidiabetic medicinal plants having insulin mimetic property

    PubMed Central

    Patel, DK; Prasad, SK; Kumar, R; Hemalatha, S

    2012-01-01

    Diabetes mellitus is one of the common metabolic disorders acquiring around 2.8% of the world's population and is anticipated to cross 5.4% by the year 2025. Since long back herbal medicines have been the highly esteemed source of medicine therefore, they have become a growing part of modern, high-tech medicine. In view of the above aspects the present review provides profiles of plants (65 species) with hypoglycaemic properties, available through literature source from various database with proper categorization according to the parts used, mode of reduction in blood glucose (insulinomimetic or insulin secretagogues activity) and active phytoconstituents having insulin mimetics activity. From the review it was suggested that, plant showing hypoglycemic potential mainly belongs to the family Leguminoseae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae and Araliaceae. The most active plants are Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia and Ficus bengalensis. The review describes some new bioactive drugs and isolated compounds from plants such as roseoside, epigallocatechin gallate, beta-pyrazol-1-ylalanine, cinchonain Ib, leucocyandin 3-O-beta-d-galactosyl cellobioside, leucopelargonidin-3- O-alpha-L rhamnoside, glycyrrhetinic acid, dehydrotrametenolic acid, strictinin, isostrictinin, pedunculagin, epicatechin and christinin-A showing significant insulinomimetic and antidiabetic activity with more efficacy than conventional hypoglycaemic agents. Thus, from the review majorly, the antidiabetic activity of medicinal plants is attributed to the presence of polyphenols, flavonoids, terpenoids, coumarins and other constituents which show reduction in blood glucose levels. The review also discusses the management aspect of diabetes mellitus using these plants and their active principles. PMID:23569923

  4. An evaluation of the inhibitory effects against rotavirus infection of edible plant extracts

    PubMed Central

    2012-01-01

    Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The developments of specific, potent and accessible antiviral treatments that restrain rotavirus infection remain important to control rotavirus disease. Methods 150 plant extracts with nutritional applications were screened in vitro on MA-104 cells for their antiviral activity against rhesus rotavirus (RRV). One extract (Aspalathus linearis (Burm.f.) R.Dahlgren) was also tested for its effect on the loss of transepithelial resistance (TER) of Caco-2 cells caused by simian rotavirus (SA-11) infection. Results Aqueous extracts of Nelumbo nucifera Gaertn. fruit, Urtica dioica L. root, Aspalathus linearis (Burm.f.) R.Dahlgren leaves, Glycyrrhiza glabra L. root and Olea europaea L. leaves were found to have strong significant antiviral activity with a 50% inhibitory concentration (IC50) < 300 μg/ml. The pure compound 18ß-glycyrrhetinic acid from Glycyrrhiza glabra was found to have the strongest antiviral activity (IC50 46 μM), followed by luteolin and vitexin from Aspalathus linearis (IC50 respectively 116 μM and 129 μM) and apigenin-7-O-glucoside from Melissa officinalis (IC50 150 μM). A combination of Glycyrrhiza glabra L. + Nelumbo nucifera Gaertn. and Urtica dioica L. + Nelumbo nucifera Gaertn. showed synergy in their anti-viral activities. Aspalathus linearis (Burm.f.) R.Dahlgren showed no positive effect on the maintenance of the TER. Conclusions These results indicate that nutritional intervention with extracts of Nelumbo nucifera Gaertn., Aspalathus linearis (Burm.f.) R.Dahlgren, Urtica dioica L., Glycyrrhiza glabra L. and Olea europaea L. might be useful in the treatment of diarrhea caused by rotavirus infection. PMID:22834653

  5. Effects of diammonium glycyrrhizinate on random skin flap survival in rats: An experimental study

    PubMed Central

    Lv, Qing-Bo; Gao, Xiang; Lin, Ding-Sheng; Chen, Yun; Cao, Bin; Zhou, Kai-Liang

    2016-01-01

    Partial necrosis of skin flaps continues to restrict the survival of local skin flaps following plastic and reconstructive surgeries. The aim of the present study was to investigate the effects of diammonium glycyrrhizinate (DG), a salt of glycyrrhetinic acid that has been widely used in the therapy of chronic hepatitis and human immunodeficiency virus infection, on random skin flap survival in rats. McFarlane flaps were established in 60 male Sprague-Dawley rats randomly divided into three groups. Group I served as the control group and was injected with saline (10 mg/kg) once per day. Group II and group III were the experimental groups, and were injected with 10 mg/kg DG once and twice per day, respectively. On day 7, the survival area of the flap was measured. Tissue samples were stained with hematoxylin and eosin and immunohistochemically evaluated. Tissue edema, neutrophil density, superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were evaluated. The mean survival areas of the flaps of group II were significantly larger when compared with those of group I (P<0.05), and the rats of group III exhibited significantly higher survival areas than group II (P<0.05). Histologic and immunohistochemical evaluation showed that microvessel development and the expression level of vascular endothelial growth factor were higher in the two experimental groups than in the control group. Furthermore, SOD activity was significantly increased (P<0.05), while the neutrophil density and MDA level were significantly reduced (P<0.05) in group II when compared with group I. Significant differences between group II and group III with regard to SOD activity and MDA level were also observed (P<0.05). Thus, DG may have a dose-dependent effect on promoting the survival of random skin flaps. PMID:27588181

  6. Aspergillus niger Enhance Bioactive Compounds Biosynthesis As Well As Expression of Functional Genes in Adventitious Roots of Glycyrrhiza uralensis Fisch.

    PubMed

    Li, Jing; Wang, Juan; Li, Jinxin; Liu, Dahui; Li, Hongfa; Gao, Wenyuan; Li, Jianli; Liu, Shujie

    2016-02-01

    In the present study, the culture conditions for the accumulation of Glycyrrhiza uralensis adventitious root metabolites in balloon-type bubble bioreactors (BTBBs) have been optimized. The results of the culture showed that the best culture conditions were a cone angle of 90° bioreactor and 0.4-0.6-0.4-vvm aeration volume. Aspergillus niger can be used as a fungal elicitor to enhance the production of defense compounds in plants. With the addition of a fungal elicitor (derived from Aspergillus niger), the maximum accumulation of total flavonoids (16.12 mg g(-1)) and glycyrrhetinic acid (0.18 mg g(-1)) occurred at a dose of 400 mg L(-1) of Aspergillus niger resulting in a 3.47-fold and 1.8-fold increase over control roots. However, the highest concentration of polysaccharide (106.06 mg g(-1)) was achieved with a mixture of elicitors (Aspergillus niger and salicylic acid) added to the medium, resulting in a 1.09-fold increase over Aspergillus niger treatment alone. Electrospray ionization tandem mass spectrometry (ESI-MS(n)) analysis was performed, showing that seven compounds were present after treatment with the elicitors, including uralsaponin B, licorice saponin B2, liquiritin, and (3R)-vestitol, only identified in the mixed elicitor treatment group. It has also been found that elicitors (Aspergillus niger and salicylic acid) significantly upregulated the expression of the cinnamate 4-hydroxylase (C4H), β-amyrin synthase (β-AS), squalene epoxidase (SE) and a cytochrome P450 monooxygenase (CYP72A154) genes, which are involved in the biosynthesis of bioactive compounds, and increased superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activity.

  7. Blockade of pathological retinal ganglion cell hyperactivity improves optogenetically evoked light responses in rd1 mice

    PubMed Central

    Barrett, John M.; Degenaar, Patrick; Sernagor, Evelyne

    2015-01-01

    Retinitis pigmentosa (RP) is a progressive retinal dystrophy that causes visual impairment and eventual blindness. Retinal prostheses are the best currently available vision-restoring treatment for RP, but only restore crude vision. One possible contributing factor to the poor quality of vision achieved with prosthetic devices is the pathological retinal ganglion cell (RGC) hyperactivity that occurs in photoreceptor dystrophic disorders. Gap junction blockade with meclofenamic acid (MFA) was recently shown to diminish RGC hyperactivity and improve the signal-to-noise ratio (SNR) of RGC responses to light flashes and electrical stimulation in the rd10 mouse model of RP. We sought to extend these results to spatiotemporally patterned optogenetic stimulation in the faster-degenerating rd1 model and compare the effectiveness of a number of drugs known to disrupt rd1 hyperactivity. We crossed rd1 mice with a transgenic mouse line expressing the light-sensitive cation channel channelrhodopsin2 (ChR2) in RGCs, allowing them to be stimulated directly using high-intensity blue light. We used 60-channel ITO multielectrode arrays to record ChR2-mediated RGC responses from wholemount, ex-vivo retinas to full-field and patterned stimuli before and after application of MFA, 18-β-glycyrrhetinic acid (18BGA, another gap junction blocker) or flupirtine (Flu, a Kv7 potassium channel opener). All three drugs decreased spontaneous RGC firing, but 18BGA and Flu also decreased the sensitivity of RGCs to optogenetic stimulation. Nevertheless, all three drugs improved the SNR of ChR2-mediated responses. MFA also made it easier to discern motion direction of a moving bar from RGC population responses. Our results support the hypothesis that reduction of pathological RGC spontaneous activity characteristic in retinal degenerative disorders may improve the quality of visual responses in retinal prostheses and they provide insights into how best to achieve this for optogenetic prostheses

  8. Connexin 40 and ATP-dependent intercellular calcium wave in renal glomerular endothelial cells.

    PubMed

    Toma, Ildikó; Bansal, Eric; Meer, Elliott J; Kang, Jung Julie; Vargas, Sarah L; Peti-Peterdi, János

    2008-06-01

    Endothelial intracellular calcium ([Ca(2+)](i)) plays an important role in the function of the juxtaglomerular vasculature. The present studies aimed to identify the existence and molecular elements of an endothelial calcium wave in cultured glomerular endothelial cells (GENC). GENCs on glass coverslips were loaded with Fluo-4/Fura red, and ratiometric [Ca(2+)](i) imaging was performed using fluorescence confocal microscopy. Mechanical stimulation of a single GENC caused a nine-fold increase in [Ca(2+)](i), which propagated from cell to cell throughout the monolayer (7.9 +/- 0.3 microm/s) in a regenerative manner (without decrement of amplitude, kinetics, and speed) over distances >400 microm. Inhibition of voltage-dependent calcium channels with nifedipine had no effect on the above parameters, but the removal of extracellular calcium reduced Delta[Ca(2+)](i) by 50%. Importantly, the gap junction uncoupler alpha-glycyrrhetinic acid or knockdown of connexin 40 (Cx40) by transfecting GENCs with Cx40 short interfering RNA (siRNA) almost completely eliminated Delta[Ca(2+)](i) and the calcium wave. Breakdown of extracellular ATP using a scavenger cocktail (apyrase and hexokinase) or nonselective inhibition of purinergic P2 receptors with suramin, had similar blocking effects. Scraping cells off along a line eliminated physical contact between cells but did not effect calcium wave propagation. Using an ATP biosensor technique, we detected a significant elevation in extracellular ATP (Delta = 76 +/- 2 microM) during calcium wave propagation, which was abolished by Cx40 siRNA treatment (Delta = 6 +/- 1 microM). These studies suggest that connexin 40 hemichannels and extracellular ATP are key molecular elements of the glomerular endothelial calcium wave, which may serve important juxtaglomerular functions.

  9. Dual-energy precursor and nuclear erythroid-related factor 2 activator treatment additively improve redox glutathione levels and neuron survival in aging and Alzheimer mouse neurons upstream of reactive oxygen species.

    PubMed

    Ghosh, Debolina; LeVault, Kelsey R; Brewer, Gregory J

    2014-01-01

    To determine whether glutathione (GSH) loss or increased reactive oxygen species (ROS) are more important to neuron loss, aging, and Alzheimer's disease (AD), we stressed or boosted GSH levels in neurons isolated from aging 3xTg-AD neurons compared with those from age-matched nontransgenic (non-Tg) neurons. Here, using titrating with buthionine sulfoximine, an inhibitor of γ-glutamyl cysteine synthetase (GCL), we observed that GSH depletion increased neuronal death of 3xTg-AD cultured neurons at increasing rates across the age span, whereas non-Tg neurons were resistant to GSH depletion until old age. Remarkably, the rate of neuron loss with ROS did not increase in old age and was the same for both genotypes, which indicates that cognitive deficits in the AD model were not caused by ROS. Therefore, we targeted for neuroprotection activation of the redox sensitive transcription factor, nuclear erythroid-related factor 2 (Nrf2) by 18 alpha glycyrrhetinic acid to stimulate GSH synthesis through GCL. This balanced stimulation of a number of redox enzymes restored the lower levels of Nrf2 and GCL seen in 3xTg-AD neurons compared with those of non-Tg neurons and promoted translocation of Nrf2 to the nucleus. By combining the Nrf2 activator together with the NADH precursor, nicotinamide, we increased neuron survival against amyloid beta stress in an additive manner. These stress tests and neuroprotective treatments suggest that the redox environment is more important for neuron survival than ROS. The dual neuroprotective treatment with nicotinamide and an Nrf2 inducer indicates that these age-related and AD-related changes are reversible.

  10. Connexin 43 Is Necessary for Salivary Gland Branching Morphogenesis and FGF10-induced ERK1/2 Phosphorylation*

    PubMed Central

    Yamada, Aya; Futagi, Masaharu; Fukumoto, Emiko; Saito, Kan; Yoshizaki, Keigo; Ishikawa, Masaki; Arakaki, Makiko; Hino, Ryoko; Sugawara, Yu; Ishikawa, Momoko; Naruse, Masahiro; Miyazaki, Kanako; Nakamura, Takashi; Fukumoto, Satoshi

    2016-01-01

    Cell-cell interaction via the gap junction regulates cell growth and differentiation, leading to formation of organs of appropriate size and quality. To determine the role of connexin43 in salivary gland development, we analyzed its expression in developing submandibular glands (SMGs). Connexin43 (Cx43) was found to be expressed in salivary gland epithelium. In ex vivo organ cultures of SMGs, addition of the gap junctional inhibitors 18α-glycyrrhetinic acid (18α-GA) and oleamide inhibited SMG branching morphogenesis, suggesting that gap junctional communication contributes to salivary gland development. In Cx43−/− salivary glands, submandibular and sublingual gland size was reduced as compared with those from heterozygotes. The expression of Pdgfa, Pdgfb, Fgf7, and Fgf10, which induced branching of SMGs in Cx43−/− samples, were not changed as compared with those from heterozygotes. Furthermore, the blocking peptide for the hemichannel and gap junction channel showed inhibition of terminal bud branching. FGF10 induced branching morphogenesis, while it did not rescue the Cx43−/− phenotype, thus Cx43 may regulate FGF10 signaling during salivary gland development. FGF10 is expressed in salivary gland mesenchyme and regulates epithelial proliferation, and was shown to induce ERK1/2 phosphorylation in salivary epithelial cells, while ERK1/2 phosphorylation in HSY cells was dramatically inhibited by 18α-GA, a Cx43 peptide or siRNA. On the other hand, PDGF-AA and PDGF-BB separately induced ERK1/2 phosphorylation in primary cultured salivary mesenchymal cells regardless of the presence of 18α-GA. Together, our results suggest that Cx43 regulates FGF10-induced ERK1/2 phosphorylation in salivary epithelium but not in mesenchyme during the process of SMG branching morphogenesis. PMID:26565022

  11. Influence of gap junction intercellular communication composed of connexin 43 on the antineoplastic effect of adriamycin in breast cancer cells

    PubMed Central

    Jiang, Guojun; Dong, Shuying; Yu, Meiling; Han, Xi; Zheng, Chao; Zhu, Xiaoguang; Tong, Xuhui

    2017-01-01

    Gap junctions (GJs) serve the principal role in the antineoplastic (cytotoxicity and induced apoptosis) effect of chemical drugs. The aim of the present study was to determine the effect of GJ intercellular communication (GJIC) composed of connexin 43 (Cx43) on adriamycin cytotoxicity in breast cancer cells. Four cell lines (Hs578T, MCF-7, MDA-MB-231 and SK-BR-3) with different degree of malignancy were used in the study. The results of western blotting and immunofluorescence revealed that, in Hs578T and MCF-7 cells, which have a low degree of malignancy, the expression levels of Cx43 and GJIC were higher than those in MDA-MB-231 and SK-BR-3 cells (which have a high degree of malignancy). In Hs578T and MCF-7 cells, where GJ could be formed, the function of GJ was modulated by a pharmacological potentiators [retinoid acid (RA)]/inhibitors [oleamide and 18-α-glycyrrhetinic acid (18-α-GA)] and small interfering RNA (siRNA). In high-density cells (where GJ was formed), enhancement of GJ function by RA increased the cytotoxicity of adriamycin, while inhibition of GJ function by oleamide/18-α-GA and siRNA decreased the cytotoxicity caused by adriamycin. Notably, the modulation of GJ did not affect the survival of cells treated with adriamycin when cells were in low density (no GJ was formed). The present study illustrated the association between GJIC and the antitumor effect of adriamycin in breast cancer cells. The cytotoxicity of adriamycin on breast cancer cells was increased when the function of gap junctions was enhanced. PMID:28356970

  12. Reductive metabolism of nabumetone by human liver microsomal and cytosolic fractions: exploratory prediction using inhibitors and substrates as marker probes.

    PubMed

    Matsumoto, Kaori; Hasegawa, Tetsuya; Koyanagi, Junichi; Takahashi, Tamiko; Akimoto, Masayuki; Sugibayashi, Kenji

    2015-06-01

    The metabolic reduction of nabumetone was examined by inhibition and correlation studies using human liver microsomes and cytosol. This reduction was observed in both fractions, with the V(max) values for reduction activity being approximately fourfold higher, and the V(max)/K(m) values approximately three-fold higher, in the microsomes than in the cytosol. The reduction of nabumetone was inhibited by 18β-glycyrrhetinic acid, an 11β-hydroxysteroid dehydrogenase (11β-HSD) inhibitor, in the microsomal fraction. The reduction activity was also inhibited by quercetin and menadione [carbonyl reductase (CBR) inhibitors], and by phenolphthalein and medroxyprogesterone acetate [potent inhibitors of aldo-keto reductase (AKR) 1C1, 1C2 and 1C4] in the cytosol. A good correlation (r² = 0.93) was observed between the reduction of nabumetone and of cortisone, as a marker of 11β-HSD activity, in the microsomal fractions. There was also an excellent relationship between reduction of nabumetone and of the AKR1C substrates, acetohexamide, and ethacrynic acid (r 2 = 0.92 and 0.93, respectively), in the cytosol fractions. However, a poor correlation was observed between the formation of 4-(6-methoxy-2-naphthyl)-butan-2-ol (MNBO) from nabumetone and CBR activity (with 4-benzoyl pyridine reduction as a CBR substrate) in the cytosol fractions (r² = 0.24). These findings indicate that nabumetone may be metabolized by 11β-HSD in human liver microsomes, and primarily by AKR1C4 in human liver cytosol, although multiple enzymes in the AKR1C subfamily may be involved. It cannot be completely denied that CBR is involved to some extent in the formation of MNBO from nabumetone in the cytosol fraction.

  13. Potential role of 20S proteasome in maintaining stem cell integrity of human bone marrow stromal cells in prolonged culture expansion

    SciTech Connect

    Lu, Li; Song, Hui-Fang; Zhang, Wei-Guo; Liu, Xue-Qin; Zhu, Qian; Cheng, Xiao-Long; Yang, Gui-Jiao; Li, Ang; Xiao, Zhi-Cheng

    2012-05-25

    Highlights: Black-Right-Pointing-Pointer Prolonged culture expansion retards proliferation and induces senescence of hBMSCs. Black-Right-Pointing-Pointer Reduced 20S proteasomal activity and expression potentially contribute to cell aging. Black-Right-Pointing-Pointer MG132-mediated 20S proteasomal inhibition induces senescence-like phenotype. Black-Right-Pointing-Pointer 18{alpha}-GA stimulates proteasomal activity and restores replicative senescence. Black-Right-Pointing-Pointer 18{alpha}-GA retains differentiation without affecting stem cell characterizations. -- Abstract: Human bone marrow stromal cells (hBMSCs) could be used in clinics as precursors of multiple cell lineages following proper induction. Such application is impeded by their characteristically short lifespan, together with the increasing loss of proliferation capability and progressive reduction of differentiation potential after the prolonged culture expansion. In the current study, we addressed the possible role of 20S proteasomes in this process. Consistent with prior reports, long-term in vitro expansion of hBMSCs decreased cell proliferation and increased replicative senescence, accompanied by reduced activity and expression of the catalytic subunits PSMB5 and PSMB1, and the 20S proteasome overall. Application of the proteasome inhibitor MG132 produced a senescence-like phenotype in early passages, whereas treating late-passage cells with 18{alpha}-glycyrrhetinic acid (18{alpha}-GA), an agonist of 20S proteasomes, delayed the senescence progress, enhancing the proliferation and recovering the capability of differentiation. The data demonstrate that activation of 20S proteasomes assists in counteracting replicative senescence of hBMSCs expanded in vitro.

  14. The effect of water loading on the urinary ratio of cortisone to cortisol in healthy subjects and a new approach to the evaluation of the ratio as an index for in vivo human 11β-hydroxysteroid dehydrogenase 2 activity.

    PubMed

    Yokokawa, Akitomo; Takasaka, Toru; Shibasaki, Hiromi; Kasuya, Yasuji; Kawashima, Soko; Yamada, Akira; Furuta, Takashi

    2012-10-01

    Factors that give rise to a large variation in the urinary ratio of free cortisone to cortisol (UFE/UFF) were investigated to accurately estimate 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) activity in humans in vivo. A water loading test was first carried out in two healthy subjects to examine the effect of water intake or urine volume on the urinary ratio of free cortisone to cortisol (UFE/UFF). The ratio was found to increase by water loading. We also examined urinary concentrations and amounts of cortisol, cortisone, creatinine, Na(+), K(+), and Cl(-), and urine volume, as possible factors affecting the urinary ratio (UFE/UFF), in 60 urine samples obtained from 15 healthy volunteers. Among these factors tested, the urinary concentration of cortisol was most highly correlated with the UFE/UFF ratio (r=-0.858), indicating that the in vivo activity of 11β-HSD2 (UFE/UFF) should fluctuate with the changes of the urinary concentration of cortisol. Based on the findings, we proposed a new estimation method of in vivo activity of 11β-HSD2 in humans, using the UFE/UFF ratio correlated with the urinary concentration of cortisol (UFE/UFF-cortisol concentration). Taking into consideration the intra-individual variabilities in the urinary concentration of cortisol, there were no significant within-day variations in 11β-HSD2 activity. The findings indicate that 11β-HSD2 activities can be accurately evaluated by simply measuring free cortisol and cortisone concentrations in spot urine samples. Furthermore, administrations of glycyrrhetinic acid in three healthy volunteers were performed to confirm the usefulness of the present assessment for the activity of 11β-HSD2.

  15. Phase transitions in freeze-dried systems - quantification using in situ synchrotron X-ray diffractometry

    SciTech Connect

    Varshney, Dushyant B.; Sundaramurthi, Prakash; Kumar, Satyendra; Shalaev, Evgenyi Y.; Kang, Shin-Woong; Gatlin, Larry A.; Suryanarayanan, Raj

    2009-09-02

    The purpose is: (1) To develop a synchrotron X-ray diffraction (SXRD) method to monitor phase transitions during the entire freeze-drying cycle. Aqueous sodium phosphate buffered glycine solutions with initial glycine to buffer molar ratios of 1:3 (17:50 mM), 1:1 (50 mM) and 3:1 were utilized as model systems. (2) To investigate the effect of initial solute concentration on the crystallization of glycine and phosphate buffer salt during lyophilization. Phosphate buffered glycine solutions were placed in a custom-designed sample cell for freeze-drying. The sample cell, covered with a stainless steel dome with a beryllium window, was placed on a stage capable of controlled cooling and vacuum drying. The samples were cooled to -50 C and annealed at -20 C. They underwent primary drying at -25 C under vacuum until ice sublimation was complete and secondary drying from 0 to 25 C. At different stages of the freeze-drying cycle, the samples were periodically exposed to synchrotron X-ray radiation. An image plate detector was used to obtain time-resolved two-dimensional SXRD patterns. The ice, {beta}-glycine and DHPD phases were identified based on their unique X-ray peaks. When the solutions were cooled and annealed, ice formation was followed by crystallization of disodium hydrogen phosphate dodecahydrate (DHPD). In the primary drying stage, a significant increase in DHPD crystallization followed by incomplete dehydration to amorphous disodium hydrogen phosphate was evident. Complete dehydration of DHPD occurred during secondary drying. Glycine crystallization was inhibited throughout freeze-drying when the initial buffer concentration (1:3 glycine to buffer) was higher than that of glycine. A high-intensity X-ray diffraction method was developed to monitor the phase transitions during the entire freeze-drying cycle. The high sensitivity of SXRD allowed us to monitor all the crystalline phases simultaneously. While DHPD crystallizes in frozen solution, it dehydrates

  16. The influence of oxalate-promoted growth of saponite and talc crystals

    USGS Publications Warehouse

    Schumann, Dirk; Hartman, Hyman; Eberl, Dennis D.; Sears, S. Kelly; Hesse, Reinhard; Vali, Hojatollah

    2013-01-01

    The intercalating growth of new silicate layers or metal hydroxide layers in the interlayer space of other clay minerals is known from various mixed-layer clay minerals such as illite-smectite (I-S), chlorite-vermiculite, and mica-vermiculite. In a recent study, the present authors proposed that smectite-group minerals can be synthesized from solution as new 2:1 silicate layers within the low-charge interlayers of rectorite. That study showed how oxalate catalyzes the crystallization of saponite from a silicate gel at low temperatures (60ºC) and ambient pressure. As an extension of this work the aim of the present study was to test the claim that new 2:1 silicate layers can be synthesized as new intercalating layers in the low-charge interlayers of rectorite and whether oxalate could promote such an intercalation synthesis. Two experiments were conducted at 60ºC and atmospheric pressure. First, disodium oxalate solution was added to a suspension of rectorite in order to investigate the effects that oxalate anions have on the structure of rectorite. In a second experiment, silicate gel of saponitic composition (calculated interlayer charge −0.33 eq/O10(OH)2) was mixed with a suspension of rectorite and incubated in disodium oxalate solution. The synthesis products were extracted after 3 months and analyzed by X-ray diffraction and high-resolution transmission electron microscopy (HRTEM). The treatment of ultrathin sections with octadecylammonium (nC = 18) cations revealed the presence of 2:1 layer silicates with different interlayer charges that grew from the silicate gel. The oxalate-promoted nucleation of saponite and talc crystallites on the rectorite led to the alteration and ultimately to the destruction of the rectorite structure. The change was documented in HRTEM lattice-fringe images. The crystallization of new 2:1 layer silicates also occurred within the expandable interlayers of rectorite but not as new 2:1 silicate layers parallel to the previous 2

  17. Mitigation of Hydrogen Gas Generation from the Reaction of Water with Uranium Metal in K Basins Sludge

    SciTech Connect

    Sinkov, Sergey I.; Delegard, Calvin H.; Schmidt, Andrew J.

    2010-01-29

    Means to decrease the rate of hydrogen gas generation from the chemical reaction of uranium metal with water were identified by surveying the technical literature. The underlying chemistry and potential side reactions were explored by conducting 61 principal experiments. Several methods achieved significant hydrogen gas generation rate mitigation. Gas-generating side reactions from interactions of organics or sludge constituents with mitigating agents were observed. Further testing is recommended to develop deeper knowledge of the underlying chemistry and to advance the technology aturation level. Uranium metal reacts with water in K Basin sludge to form uranium hydride (UH3), uranium dioxide or uraninite (UO2), and diatomic hydrogen (H2). Mechanistic studies show that hydrogen radicals (H·) and UH3 serve as intermediates in the reaction of uranium metal with water to produce H2 and UO2. Because H2 is flammable, its release into the gas phase above K Basin sludge during sludge storage, processing, immobilization, shipment, and disposal is a concern to the safety of those operations. Findings from the technical literature and from experimental investigations with simple chemical systems (including uranium metal in water), in the presence of individual sludge simulant components, with complete sludge simulants, and with actual K Basin sludge are presented in this report. Based on the literature review and intermediate lab test results, sodium nitrate, sodium nitrite, Nochar Acid Bond N960, disodium hydrogen phosphate, and hexavalent uranium [U(VI)] were tested for their effects in decreasing the rate of hydrogen generation from the reaction of uranium metal with water. Nitrate and nitrite each were effective, decreasing hydrogen generation rates in actual sludge by factors of about 100 to 1000 when used at 0.5 molar (M) concentrations. Higher attenuation factors were achieved in tests with aqueous solutions alone. Nochar N960, a water sorbent, decreased hydrogen

  18. A LC-ESI-MS method for the simultaneous determination of madecassoside and its metabolite madecassic acid in rat plasma: comparison pharmacokinetics in normal and collagen-induced arthritic rats.

    PubMed

    Wang, Ting; Leng, Dan-Dan; Gao, Fei-Fei; Jiang, Chun-Jie; Xia, Yu-Feng; Dai, Yue

    2014-12-01

    To develop a simple and highly sensitive high performance liquid chromatography with electrospray ionization mass spectrometric (LC-ESI-MS) method for the simultaneous determination of madecassoside and its major metabolite madecassic acid in rat plasma, and compare the pharmacokinetics of the two compounds in normal and collagen-induced arthritis (CIA) rats. Glycyrrhetinic acid was used as the internal standard (IS). Chromatographic separation was accomplished on an Inertsil ODS-3 column, using a gradient elution with the mobile phase composed of acetonitrile and water acidified with 0.1% (V/V) formic acid. Detection was achieved by ESI-MS under the negative selected ion monitoring (SIM) mode. In normal and CIA rats, madecassoside (30 mg·kg(-1)) was orally administered for 21 consecutive days from the day of arthritis onset. For madecassoside, the linear range was 10-1 000 ng·mL(-1) with the square regression coefficient (r) of 0.998 9, while for madecassic acid, the linear range was 10-500 ng·mL(-1) with the square regression coefficient (r) of 0.996 1. The lower limit of quantification was 10 ng·mL(-1) for both analytes. The intra- and inter-day precision ranged from 1.78% to 13.42% for madecassoside and 2.30% to 14.90% for madecassic acid, and the accuracy was between -0.95% and 6.30% for madecassoside and between -1.48% and 5.34% for madecassic acid. The average recoveries of madecassoside, madecassic acid and IS from spiked plasma samples were > 81%. The developed method was successfully applied to the pharmacokinetic study of madecassoside and madecassic acid in rats after an oral administration of madecassoside. During initial 7 days of dosing, the cmax and AUC of madecassoside were greatly decreased and Vd/F was markedly increased in CIA rats, and no significant difference was observed on the first day of dosing. In contrast, the T1/2, cmax and AUC of madecassic acid were significantly increased, and Ke of madecassic acid was greatly decreased in CIA

  19. Gap Junction Communication and the Propagation of Bystander Effects Induced by Microbeam Irradiation in Human Fibroblast Cultures: The Impact of Radiation Quality

    PubMed Central

    Autsavapromporn, Narongchai; Suzuki, Masao; Funayama, Tomoo; Usami, Noriko; Plante, Ianik; Yokota, Yuichiro; Mutou, Yasuko; Ikeda, Hiroko; Kobayashi, Katsumi; Kobayashi, Yasuhiko; Uchihori, Yukio; Hei, Tom K.; Azzam, Edouard I.; Murakami, Takeshi

    2014-01-01

    Understanding the mechanisms underlying the bystander effects of low doses/low fluences of low- or high-linear energy transfer (LET) radiation is relevant to radiotherapy and radiation protection. Here, we investigated the role of gap-junction intercellular communication (GJIC) in the propagation of stressful effects in confluent normal human fibroblast cultures wherein only 0.036–0.144% of cells in the population were traversed by primary radiation tracks. Confluent cells were exposed to graded doses from monochromatic 5.35 keV X ray (LET ~6 keV/μm), 18.3 MeV/u carbon ion (LET ~103 keV/μm), 13 MeV/u neon ion (LET ~380 keV/μm) or 11.5 MeV/u argon ion (LET ~1,260 keV/μm) microbeams in the presence or absence of 18-α-glycyrrhetinic acid (AGA), an inhibitor of GJIC. After 4 h incubation at 37°C, the cells were subcultured and assayed for micronucleus (MN) formation. Micronuclei were induced in a greater fraction of cells than expected based on the fraction of cells targeted by primary radiation, and the effect occurred in a dose-dependent manner with any of the radiation sources. Interestingly, MN formation for the heavy-ion microbeam irradiation in the absence of AGA was higher than in its presence at high mean absorbed doses. In contrast, there were no significant differences in cell cultures exposed to X-ray microbeam irradiation in presence or absence of AGA. This showed that the inhibition of GJIC depressed the enhancement of MN formation in bystander cells from cultures exposed to high-LET radiation but not low-LET radiation. Bystander cells recipient of growth medium harvested from 5.35 keV X-irradiated cultures experienced stress manifested in the form of excess micronucleus formation. Together, the results support the involvement of both junctional communication and secreted factor(s) in the propagation of radiation-induced stress to bystander cells. They highlight the important role of radiation quality and dose in the observed effects. PMID:23987132

  20. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model

    PubMed Central

    Sovadinova, Iva; Babica, Pavel; Böke, Hatice; Kumar, Esha; Wilke, Andrew; Park, Joon-Suk; Trosko, James E.; Upham, Brad L.

    2015-01-01

    Dysregulation of gap junctional intercellular communication (GJIC) has been associated with different pathologies, including cancer; however, molecular mechanisms regulating GJIC are not fully understood. Mitogen Activated Protein Kinase (MAPK)-dependent mechanisms of GJIC-dysregulation have been well-established, however recent discoveries have implicated phosphatidylcholine-specific phospholipase C (PC-PLC) in the regulation of GJIC. What is not known is how prevalent these two signaling mechanisms are in toxicant/toxin-induced dysregulation of GJIC, and do toxicants/toxins work through either signaling mechanisms or both, or through alternative signaling mechanisms. Different chemical toxicants were used to assess whether they dysregulate GJIC via MEK or PC-PLC, or both Mek and PC-PLC, or through other signaling pathways, using a pluripotent rat liver epithelial oval-cell line, WB-F344. Epidermal growth factor, 12-O-tetradecanoylphorbol-13-acetate, thrombin receptor activating peptide-6 and lindane regulated GJIC through a MEK1/2-dependent mechanism that was independent of PC-PLC; whereas PAHs, DDT, PCB 153, dicumylperoxide and perfluorodecanoic acid inhibited GJIC through PC-PLC independent of Mek. Dysregulation of GJIC by perfluorooctanoic acid and R59022 required both MEK1/2 and PC-PLC; while benzoylperoxide, arachidonic acid, 18β-glycyrrhetinic acid, perfluorooctane sulfonic acid, 1-monolaurin, pentachlorophenol and alachlor required neither MEK1/2 nor PC-PLC. Resveratrol prevented dysregulation of GJIC by toxicants that acted either through MEK1/2 or PC-PLC. Except for alachlor, resveratrol did not prevent dysregulation of GJIC by toxicants that worked through PC-PLC-independent and MEK1/2-independent pathways, which indicated at least two other, yet unidentified, pathways that are involved in the regulation of GJIC. In conclusion: the dysregulation of GJIC is a contributing factor to the cancer process; however the underlying mechanisms by which gap

  1. Modulation of human cell responses to space radiation by gap-junction communication

    NASA Astrophysics Data System (ADS)

    Autsavapromporn, Narongchai; de Toledo, Sonia M.; Buonanno, Manuela; Yang, Zhi; Harris, Andrew; Jay-Gerin, Jean-Paul; Azzam, Edouard

    Understanding the biological effects of space radiation and their underlying mechanism is critical to estimating the health risk associated with human exploration of space. A coordinated interaction of multiple cellular processes is likely involved in the sensing and processing of stressful effects induced by different types of space radiation. Here, we focused on the role of gap-junction intercellular communication (GJIC) in responses of human cells exposed to 1 GeV/n protons or 56 Fe-ions. We compared the results with data obtained in human cells exposed, in parallel, to γ-rays or α-particles. As expected, a higher level of cell killing and DNA damage, per unit dose, was induced in confluent, density-inhibited cells (98% in G0 /G1 ) exposed to α-particles or energetic 56 Fe-ions than γ-rays or protons. Strikingly, greatly attenuated effects occurred when sub-confluent cultures, synchronized in G0 /G1 ,were exposed to 56 Fe-ions. These data suggest that direct intercellular communication is involved in the effects of high linear energy transfer (LET) 56 Fe-ions. To examine the role of gap-junctions in propagating stressful effect, confluent cultures were exposed to 56 Fe-ions or α-particles and incubated for various time periods at 37° C in the presence or absence of the gap-junction inhibitor α-glycyrrhetinic acid (AGA). No repair of potentially lethal radiation damage occurred in cells incubated in the absence of AGA. In contrast, inhibition of functional GJIC significantly enhanced clonogenic survival of irradiated cells. To test the role of junctional channel permeability in the observed effects, we used human adenocarcinoma (HeLa) cells in which specific connexins (Cx) can be expressed in the absence of endogenous connexins. Whereas HeLa cells with selective inducible expression of Cx26 gap-junctions promoted radiation toxic effects, expression of Cx32 junctional channels in HeLa cells promoted pro-survival effects. Experiments are in progress to

  2. Purification, characterization and NNK carbonyl reductase activities of 11beta-hydroxysteroid dehydrogenase type 1 from human liver: enzyme cooperativity and significance in the detoxification of a tobacco-derived carcinogen.

    PubMed

    Maser, Edmund; Friebertshäuser, Jutta; Völker, Bernhard

    2003-02-01

    11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD 1) physiologically catalyzes the interconversion of receptor-active 11-hydroxy glucocorticoids (cortisol) to their receptor-inactive 11-oxo metabolites (cortisone), thereby acting as important pre-receptor control device in regulating access of glucocorticoid hormones to the glucocorticoid receptor. Evidence is emerging that 11beta-HSD 1 fulfills an additional role in the detoxification of non-steroidal carbonyl compounds, by catalyzing their reduction to the corresponding hydroxy derivatives that are easier to conjugate and eliminate. Whereas a number of methods were ineffective in purifying 11beta-HSD 1 from human liver, this membrane-bound enzyme was successfully obtained in an active state by a purification procedure that took advantage of a gentle solubilization method as well as providing a favourable detergent surrounding during the various chromatographic steps. We could demonstrate that 11beta-HSD 1 is active as a dimeric enzyme which exhibits cooperativity with cortisone and dehydrocorticosterone (11-oxoreducing activity) as substrates. Accordingly, this enzyme dynamically adapts to low (nanomolar) as well as to high (micromolar) substrate concentrations, thereby providing the fine tuning required as a consequence of great variations in circadian plasma glucocorticoid levels. Due to this kinetic peculiarity, 11beta-HSD 1 is also able to even metabolize nanomolar concentrations of the tobacco-specific nitrosamine 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK), a fact which is important in view of the relatively low levels of this carcinogen observed in smokers. Finally, 11beta-HSD 1 is potently (in nM concentrations) inhibited by glycyrrhetinic acid, the main constituent of licorice. Licorice, however, in addition to being a confectionary, serves as a major cigarette additive, which is used in cigarette manufacturing as a taste and flavour intensifier. Hence, licorice exposure may affect NNK

  3. Pharmacokinetics of Active Components of Yokukansan, a Traditional Japanese Herbal Medicine after a Single Oral Administration to Healthy Japanese Volunteers: A Cross-Over, Randomized Study

    PubMed Central

    Kitagawa, Hiroyuki; Munekage, Masaya; Ichikawa, Kengo; Fukudome, Ian; Munekage, Eri; Takezaki, Yuka; Matsumoto, Takashi; Igarashi, Yasushi; Hanyu, Haruo; Hanazaki, Kazuhiro

    2015-01-01

    Context Yokukansan (YKS) is a traditional Japanese herbal medicine called kampo medicine in Japan. Its extract comprises seven crude drugs: Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix. YKS is used to treat neurosis, insomnia, as well as behavioral and psychological symptoms of dementia. Objective To confirm the exposure and pharmacokinetics of the active components of YKS in healthy volunteers. Design, Setting, and Participants A randomized, open-label, 3-arm, 3-period, crossover trial was conducted on 21 healthy Japanese volunteers at the Kochi Medical University between May 2012 and November 2012. Interventions Single oral administration of YKS (2.5 g, 5.0 g, or 7.5 g/day) during each period. Main Outcome Measure Plasma concentrations of three active compounds in YKS, namely 18β-glycyrrhetinic acid (GA), geissoschizine methyl ether (GM), and hirsuteine (HTE). Results The mean maximum plasma concentrations (Cmax) of GM and HTE increased dose-dependently (ranges: 0.650–1.98 ng/mL and 0.138–0.450 ng/mL, respectively). The times to maximum plasma concentration after drug administration (tmax) were 0.500 h for GM and 0.975–1.00 h for HTE. The apparent elimination half-lives (t1/2) were 1.72–1.95 h for GM and 2.47–3.03 h for HTE. These data indicate the rapid absorption and elimination of GM and HTE. On the other hand, the Cmax, tmax, and t1/2 of GA were 57.7–108 ng/mL, 8.00–8.01 h, and 9.39–12.3 h, respectively. Conclusion We demonstrated that pharmacologically active components of YKS are detected in humans. Further, we determined the pharmacokinetics of GM, HTE, and GA. This information will be useful to elucidate the pharmacological effects of YKS. Trial Registration Japan Pharmaceutical Information Center JAPIC CTI-121811 PMID:26151135

  4. Pharmacological characterisation of capsaicin-induced relaxations in human and porcine isolated arteries

    PubMed Central

    Gupta, Saurabh; Lozano-Cuenca, Jair; Villalón, Carlos M.; de Vries, René; Garrelds, Ingrid M.; Avezaat, Cees J. J.; van Kats, Jorge P.; Saxena, Pramod R.

    2007-01-01

    Capsaicin, a pungent constituent from red chilli peppers, activates sensory nerve fibres via transient receptor potential vanilloid receptors type 1 (TRPV1) to release neuropeptides like calcitonin gene-related peptide (CGRP) and substance P. Capsaicin-sensitive nerves are widely distributed in human and porcine vasculature. In this study, we examined the mechanism of capsaicin-induced relaxations, with special emphasis on the role of CGRP, using various pharmacological tools. Segments of human and porcine proximal and distal coronary arteries, as well as cranial arteries, were mounted in organ baths. Concentration response curves to capsaicin were constructed in the absence or presence of the CGRP receptor antagonist olcegepant (BIBN4096BS, 1 μM), the neurokinin NK1 receptor antagonist L-733060 (0.5 μM), the voltage-sensitive calcium channel blocker ruthenium red (100 μM), the TRPV1 receptor antagonist capsazepine (5 μM), the nitric oxide synthetase inhibitor Nω-nitro-l-arginine methyl ester HCl (l-NAME; 100 μM), the gap junction blocker 18α-glycyrrhetinic acid (10 μM), as well as the RhoA kinase inhibitor Y-27632 (1 μM). Further, we also used the K+ channel inhibitors 4-aminopyridine (1 mM), charybdotoxin (0.5 μM) + apamin (0.1 μM) and iberiotoxin (0.5 μM) + apamin (0.1 μM). The role of the endothelium was assessed by endothelial denudation in distal coronary artery segments. In distal coronary artery segments, we also measured levels of cyclic adenosine monophosphate (cAMP) after exposure to capsaicin, and in human segments, we also assessed the amount of CGRP released in the organ bath fluid after exposure to capsaicin. Capsaicin evoked concentration-dependent relaxant responses in precontracted arteries, but none of the above-mentioned inhibitors did affect these relaxations. There was no increase in the cAMP levels after exposure to capsaicin, unlike after (exogenously administered) α-CGRP. Interestingly, there were

  5. The Importance of Connexin Hemichannels During Chondroprogenitor Cell Differentiation in Hydrogel Versus Microtissue Culture Models

    PubMed Central

    Schrobback, Karsten; Klein, Travis Jacob

    2015-01-01

    Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell–cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell–cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5′-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular

  6. Structural restoration of nematodes and acanthocephalans fixed in high percentage alcohol using DESS solution and rehydration.

    PubMed

    Naem, Soraya; Pagan, Christopher; Nadler, Steven A

    2010-08-01

    Ninety-five percent ethanol is the most widely used field and laboratory preservative for nematodes and other helminth specimens intended for use in molecular systematics. Preservation of nematodes in high-concentration alcohols results in structural dehydration artifacts, including shrinkage and body surface distortions sufficient to obscure features required for morphological identification and analysis, thereby compromising precise morphometrics. However, treating dehydrated nematodes using a solution of DMSO, disodium EDTA, and NaCl, followed by rehydration in water produces marked improvements in specimen shape and surface features, resulting from diffusion of water into the tissues and pseudocoelom as the internal salt concentration is reduced. Following rehydration, tissue samples can be obtained for molecular research and individuals can be fixed for morphological examination. This treatment method is demonstrated for species of 3 nematode genera that vary substantially in body size ( Baylisascaris , Uncinaria , and Bidigiticauda ). The method also works on nematodes that have been cut in half, provided the individuals are large enough to be folded and clamped during treatment. This method appears promising for other helminths, although for an acanthocephalan, the treatment restored the body surface but failed to reverse the retracted proboscis.

  7. In Vitro and In Vivo Evaluation of a Hydrogel Reservoir as a Continuous Drug Delivery System for Inner Ear Treatment

    PubMed Central

    Hessler, Roland; Stöver, Timo; Esser, Karl-Heinz; Möller, Martin; Lenarz, Thomas; Jolly, Claude; Groll, Jürgen; Scheper, Verena

    2014-01-01

    Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear. PMID:25105670

  8. In vitro and in vivo evaluation of a hydrogel reservoir as a continuous drug delivery system for inner ear treatment.

    PubMed

    Hütten, Mareike; Dhanasingh, Anandhan; Hessler, Roland; Stöver, Timo; Esser, Karl-Heinz; Möller, Martin; Lenarz, Thomas; Jolly, Claude; Groll, Jürgen; Scheper, Verena

    2014-01-01

    Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.

  9. Simultaneous determination of seven fluoroquinolones in royal jelly by ultrasonic-assisted extraction and liquid chromatography with fluorescence detection.

    PubMed

    Zhou, Jinhui; Xue, Xiaofeng; Chen, Fang; Zhang, Jinzhen; Li, Yi; Wu, Liming; Chen, Lanzhen; Zhao, Jing

    2009-04-01

    A method for the quantitative determination of seven fluoroquinolone antibacterial agents (FQs) used in beekeeping, viz. ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, danofloxacin, enrofloxacin, and difloxacin, in royal jelly samples was developed on the basis of high performance liquid chromatography with fluorescence detection. Sample preparation included deproteination, ultrasonic-assisted extraction with a mixed inorganic solution of monopotassium phosphate (KH(2)PO(4)) and ethylenediaminetetraacetic acid disodium salt (Na(2)EDTA), and clean-up on a solid-phase extraction cartridge. The extraction procedure was optimized with regard to the amount of inorganic solvent and the duration of sonication for royal jelly as a complicated matrix. Overall recoveries for FQs ranged from 85.9 to 99.1% for royal jelly with standard deviations between 2.79 and 6.27%. Limits of quantification were 2-40 ng/g for seven FQs in royal jelly. A total of 57 real royal jelly samples collected from beekeepers and supermarkets were analyzed. The three most abundant honeybee-use FQs, i. e. ofloxacin, ciprofloxacin, and norfloxacin, were determined in some royal jelly samples in concentrations ranging from 11.9 to 55.6 ng/g. Unexpectedly, however, difloxacin was found at concentrations of about 46.8 ng/g in one sample although it is rarely used in beekeeping. The presented method was successfully applied to quantify FQs in real royal jelly samples.

  10. Optimization of singlet oxygen production from photosensitizer-incorporated, medically relevant hydrogels.

    PubMed

    De Baróid, Áine T; McCoy, Colin P; Craig, Rebecca A; Carson, Louise; Andrews, Gavin P; Jones, David S; Gorman, Sean P

    2017-02-01

    Photodynamic therapy and photodynamic antimicrobial chemotherapy are widely used, but despite this, the relationships between fluence, wavelength of irradiation and singlet oxygen ((1) O2 ) production are poorly understood. To establish the relationships between these factors in medically relevant materials, the effect of fluence on (1) O2 production from a tetrakis(4-N-methylpyridyl)porphyrin (TMPyP)-incorporated 2-hydroxyethyl methacrylate: methyl methacrylate: methacrylic acid (HEMA: MMA:MAA) copolymer, a total energy of 50.48 J/cm(2) , was applied at varying illumination power, and times. (1) O2 production was characterized using anthracene-9,10-dipropionic acid, disodium salt (ADPA) using a recently described method. Using two light sources, a white LED array and a white halogen source, the LED array was found to produce less (1) O2 than the halogen source when the same power (over 500 - 600 nm) and time conditions were applied. Importantly, it showed that the longest wavelength Q band (590 nm) is primarily responsible for (1) O2 generation, and that a linear relationship exists between increasing power and time and the production of singlet oxygen. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 320-326, 2017.

  11. Availability of antidotes and key emergency drugs in tertiary care hospitals of Punjab and assessment of the knowledge of health care professionals in the management of poisoning cases.

    PubMed

    Arslan, Naheed; Khiljee, Sonia; Bakhsh, Allah; Ashraf, Muhammad; Maqsood, Iram

    2016-03-01

    This study was conducted to evaluate the availability of antidotes/key emergency drugs in tertiary care hospitals of the Punjab province, and to assess the knowledge of health care professionals in the stocking and administration of antidotes in the proper management of poisoning cases. Seventeen (n=17) tertiary care hospitals of Punjab Pakistan were selected. Two performas (A and B) were designed for 26 antidotes/key emergency drugs and given to the hospital pharmacists and physicians respectively. It was observed that Activated Charcoal, being the universal antidote was found only in 6 hospitals (41%). Digoxin Immune Fab, Edentate Calcium disodium and Glucagon were not available in emergency department of any hospital and even not included in the formulary of any hospital. About 80% pharmacists were aware of the method of preparation of Activated Charcoal and 85% physicians were familiar with its route of administration. Data showed that tertiary care hospitals of Punjab do not stock antidotes according to national drug policy. Moreover the study strongly suggests the development of health care centers and professional by organizing antidote awareness programs, continuous education and record keeping of poisonous cases and availability of emergency drugs around the clock.

  12. Effect of murine recombinant interleukin-5 on the cell population in guinea-pig airways.

    PubMed Central

    Iwama, T.; Nagai, H.; Suda, H.; Tsuruoka, N.; Koda, A.

    1992-01-01

    1. An intratracheal injection of murine recombinant interleukin 5 (mrIL-5, 2-15 microgram/0.25 ml/animal) induced a dose-dependent increase in the number of macrophages, eosinophils, neutrophils and epithelial cells in the bronchoalveolar lavage fluid (BALF) of guinea-pigs 24 h after administration. Bovine serum albumin (15 micrograms/0.25 ml/animal), used as a reference material, did not cause any change of this type. 2. The intratracheal administration of mrIL-5 at a dose of 15 microgram showed a tendency to increase the number of these pulmonary inflammatory cells and epithelial cells in the BALF at 12 h with a significant increase observed at 24 h. 3. Prednisolone (20 mg kg-1, i.p.) inhibited the mrIL-5-induced increase in macrophages, eosinophils, neutrophils and epithelial cells. Ketotifen (2 mg kg-1, i.p.) reduced the mrIL-5-induced increase in the eosinophil, neutrophil and epithelial cell populations. The simultaneous injection of 2% disodium cromoglycate (DSCG) into the trachea prevented the mrIL-5-induced increase in the number of airway epithelial cells, without affecting changes in the other inflammatory leukocytes. 4. These results suggest that mrIL-5 is a potent inducer of lung inflammation, in terms of increased inflammatory leukocytes and epithelial cells in guinea-pig BALF. Prednisolone, DSCG and ketotifen are effective against mrIL-5-induced pulmonary inflammation, especially the desquamation of bronchial epithelial cells. PMID:1596681

  13. Solubilization and stabilization of macular carotenoids by water soluble oligosaccharides and polysaccharides.

    PubMed

    Apanasenko, Irina E; Selyutina, Olga Yu; Polyakov, Nikolay E; Suntsova, Lyubov P; Meteleva, Elizaveta S; Dushkin, Alexander V; Vachali, Preejith; Bernstein, Paul S

    2015-04-15

    Xanthophyll carotenoids zeaxanthin and lutein play a special role in the prevention and treatment of visual diseases. These carotenoids are not produced by the human body and must be consumed in the diet. On the other hand, extremely low water solubility of these carotenoids and their instability restrict their practical application as components of food or medicinal formulations. Preparation of supramolecular complexes of zeaxanthin and lutein with glycyrrhizic acid, its disodium salt and the natural polysaccharide arabinogalactan allows one to minimize the aforementioned disadvantages when carotenoids are used in food processing as well as for production of therapeutic formulations with enhanced solubility and stability. In the present study, the formation of supramolecular complexes was investigated by NMR relaxation, surface plasmon resonance (SPR) and optical absorption techniques. The complexes increase carotenoid solubility more than 1000-fold. The kinetics of carotenoid decay in reactions with ozone molecules, hydroperoxyl radicals and metal ions were measured in water and organic solutions, and significant increases in oxidation stability of lutein and zeaxanthin in arabinogalactan and glycyrrhizin complexes were detected.

  14. Solubilization and Stabilization of Macular Carotenoids by Water Soluble Oligosaccharides and Polysaccharides

    PubMed Central

    Apanasenko, Irina E.; Selyutina, Olga Yu.; Polyakov, Nikolay E.; Suntsova, Lyubov P.; Meteleva, Elizaveta S.; Dushkin, Alexander V.; Vachali, Preejith; Bernstein, Paul S.

    2015-01-01

    Xanthophyll carotenoids zeaxanthin and lutein play a special role in the prevention and treatment of visual diseases. These carotenoids are not produced by the human body and must be consumed in the diet. On the other hand, extremely low water solubility of these carotenoids and their instability restrict their practical application as components of food or medicinal formulations. Preparation of supramolecular complexes of zeaxanthin and lutein with glycyrrhizic acid, its disodium salt and the natural polysaccharide arabinogalactan allows one to minimize the aforementioned disadvantages when carotenoids are used in food processing as well as for production of therapeutic formulations with enhanced solubility and stability. In the present study, the formation of supramolecular complexes was investigated by NMR relaxation, surface plasmon resonance (SPR) and optical absorption techniques. The complexes increase carotenoid solubility more than 1000-fold. The kinetics of carotenoid decay in reactions with ozone molecules, hydroperoxyl radicals and metal ions were measured in water and organic solutions, and significant increases in oxidation stability of lutein and zeaxanthin in arabinogalactan and glycyrrhizin complexes were detected. PMID:25527162

  15. Melasma: treatment strategy.

    PubMed

    Sehgal, Virendra N; Verma, Prashant; Srivastava, Govind; Aggarwal, Ashok K; Verma, Sangeeta

    2011-12-01

    Melasma, a hypermelanosis of the face, is a common skin problem of middle-aged women of all racial groups, especially with dark complexion. Its precise etio-pathogenesis is evasive, genetic influences, exposure to sunlight, pregnancy, oral contraceptives, estrogen-progesterone therapies, thyroid dysfunction, cosmetics, and drugs have been proposed. Centro-facial, malar, and mandibular are well-recognized. Epidermal pigmentation appears brown/black, while dermal is blue in color, and can be distinguished by Wood's lamp illumination. The difference may be inapparent with mixed type of melasma in skin types V and VI. An increase in melanin in epidermis: basal and suprabasal layers and/or dermis is the prime defect. There is an increased expression of tyrosinase related protein-1 involved in eumelanin synthesis. The use of broad-spectrum sunscreen is important, lightening agents like retinoic acid (tretinoin), azelaic acid, and combination therapies containing hydroquinone, tretinoin, and corticosteroids, have been used in the treatment of melasma, and are thought to have increased efficacy as compared with monotherapy. Quasi-drugs, placental extracts, ellagic acid, chamomilla extract, butylresorcinol, tranexamic acid, methoxy potassium salicylate, adenosine monophosphate disodium salt, dipropyl-biphenyl-2,2'-diol, (4-hydroxyphenyl)-2-butanol, and tranexamic acid cetyl ester hydrochloride, in addition to kojic and ascorbic acid have been used. Chemical peeling is a good adjunct. Laser treatment is worthwhile.

  16. Use of sodium polyphosphates with different linear lengths in the production of spreadable processed cheese.

    PubMed

    Nagyová, G; Buňka, F; Salek, R N; Černíková, M; Mančík, P; Grůber, T; Kuchař, D

    2014-01-01

    The objective of this study was to describe the dependence of textural properties (hardness, cohesiveness, and relative adhesiveness) of processed cheese spreads on the proportion of disodium phosphate (DSP), tetrasodium diphosphate (TSPP), and sodium salts of polyphosphate in ternary mixtures of emulsifying salts. Sodium salts of polyphosphate with different mean lengths (n ≈ 5, 9, 13, 20, and 28) were used. Pentasodium triphosphate (PSTP) was used instead of TSPP in the second part of the study. Products with and without pH adjustment were tested (the target pH value was 5.60-5.80). Textural properties of the processed cheese were observed after 2, 9, and 30 d of storage at 6°C. Hardness of the processed cheese with a low content of polyphosphate increased at a specific DSP:TSPP ratio (~1:1 to 3:4). This trend was the same for all the polyphosphates used; only the absolute values of texture parameters were different. The same trends were observed in the ternary mixtures with PSTP, showing lower final values of hardness compared with samples containing TSPP. Hardness and cohesiveness decreased and relative adhesiveness increased in the samples with increased pH values and vice versa; the main trend remained unchanged.

  17. Effect of emulsifying salts on the physicochemical properties of processed cheese made from Mozzarella.

    PubMed

    Chen, L; Liu, H

    2012-09-01

    The aim of this study was to investigate the effect of different types and concentrations of emulsifying salts (trisodium citrate, tetrasodium pyrophosphate, sodium tripolyphosphate, sodium hexametaphosphate, and disodium orthophosphate) on the physicochemical properties of processed cheese. The physicochemical composition, texture profile, degree of casein dissociation, fat particle size, color, and nuclear magnetic resonance profile (NMR) of processed cheese were determined. Hardness, degree of casein dissociation, and pH increased as the concentration of emulsifying salts increased. The fat particle size of processed cheese was significantly influenced by the type of emulsifying salts, with processed cheese made with sodium hexametaphosphate having larger particles (4.68 µm) than cheeses made with the other salts (from 2.71 to 3.30 µm). The processed cheese prepared with trisodium citrate was whiter than those prepared with the other emulsifying salts. The NMR analysis showed that the relaxation time of processed cheese of 10 to 100 ms accounted for a major proportion, indicating that the moisture in processed cheese was mainly bound water combined with the fat globule and hydrated casein.

  18. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-01-01

    Gateways to Clinical Trials are a guide to the most recent clinical trials in current literature and congresses. The data the following tables have been retrieved from the Clinical Trials Knowledge Area of Prous Science Integrity, the drug discovery and development portal, http://integrity.prous.com. This issues focuses on the following selection of drugs: 4'-Thio-ara-C, 5-methyltetrahydrofolate; ABT-089, AD-237, AF-37702, alvocidib hydrochloride, apricitabine, armodafinil, atrasentan, AVE-5883, avian influenza vaccine, azimilide hydrochloride; Banoxantrone, BIBF-1120; CD34+ cells, certolizumab pegol, CHIR-258, cilansetron, CoFactor, CX-3543, cystemustine; D-003, dexloxiglumide, DMXB-anabaseine; Ecogramostim, elcometrine, elcometrine/ethinylestradiol, etravirine; Fenretinide, fingolimod hydrochloride, fospropofol disodium; Gaboxadol, gestodene, glutamine; Human insulin, hyaluronic acid; Incyclinide, indacaterol, ispronicline, istradefylline; Labradimil, lamifiban, lapatinib, L-arginine hydrochloride, liposomal cisplatin, liposome encapsulated paclitaxel, LY-517717; Manidipine hydrochloride/delapril hydrochloride, maraviroc, MBP(82-98), MD-0727, MDX-214, melanotan I, MMR vaccine; Nacystelyn, nalfurafine hydrochloride, nibentan, nilotinib, NK-105; OBI-1, oblimersen sodium, olmesartan medoxomil, olmesartan medoxomil/hydrochlorothiazide, oregovomab; Pexelizumab, PG-116800, PG-CPT, PHA-794428, prasugrel; RC-3095, rDNA insulin, RFB4(dsFv)-PE38, rhEndostatin, rhenium Re-186 etidronate, rhGM-CSF, roflumilast, romidepsin; Sarcosine, SGLU1, SGN-40, succinobucol; TAU, teduglutide, telatinib, tesofensine, tipifarnib, tirapazamine, TKA-731, tolvaptan, trabectedin; Vaccimel, vatalanib succinate, velafermin, vildagliptin, vinflunine; XP-19986; YM-155.

  19. Gateways to clinical trials.

    PubMed

    Bayés, M; Rabasseda, X; Prous, J R

    2007-11-01

    1-Octanol, 9vPnC-MnCc; Abiraterone acetate, Adalimumab, Adefovir dipivoxil, Alemtuzumab, Aliskiren fumarate, Aminolevulinic acid hexyl ester, Amlodipine besylate/atorvastatin calcium, Amrubicin hydrochloride, Anakinra, Aripiprazole, ARRY-520, AS-1404, Asimadoline, Atazanavir sulfate, AVE-0277, Azelnidipine; Bevacizumab, Bimatoprost, Boceprevir, Bortezomib, Bosentan, Botulinum toxin type B; Certolizumab pegol, Cetuximab, Clevudine, Contusugene ladenovec, CP-751871, Crofelemer, Cypher, CYT006-AngQb; Darbepoetin alfa, Desmopressin, Dexlansoprazole, DG-041; E-5555, Ecogramostim, Entecavir, Erlotinib hydrochloride, Escitalopram oxalate, Eszopiclone, Everolimus, Ezetimibe, Ezetimibe/simvastatin; Falecalcitriol, Fampridine, Fesoterodine fumarate, Fingolimod hydrochloride; Gefitinib, Ghrelin (human), GS-7904L, GV-1001; HT-1001; Insulin detemir, ISIS-112989, Istradefylline; Laquinimod sodium, Latanoprost/timolol maleate, Lenalidomide, Levobetaxolol hydrochloride, Liposomal doxorubicin, Liposomal morphine sulfate, Lubiprostone, Lumiracoxib, LY-518674; MEM-1003, Mesna disulfide, Mipomersen sodium, MM-093, Mycophenolic acid sodium salt; Naptumomab estafenatox, Natalizumab; Olmesartan medoxomil, Olmesartan medoxomil/hydrochlorothiazide; Paclitaxel nanoparticles, Paclitaxel poliglumex, Pasireotide, Pazufloxacin mesilate, Pegfilgrastim, Peginterferon alfa-2a, Peginterferon alfa-2b, Peginterferon alfa-2b/ribavirin, Pegvisomant, Pemetrexed disodium, Pimagedine, Pimecrolimus, Pramlintide acetate, Prasterone, Pregabalin, Prulifloxacin; QAE-397; Rec-15/2615, RFB4(dsFv)-PE38, rhGAD65, Roflumilast, Romiplostim, Rosuvastatin calcium, Rotigotine, Rupatadine fumarate; Safinamide mesilate, SIR-Spheres, Sitagliptin phosphate, Sodium phenylacetate, Sodium phenylacetate/Sodium benzoate, Sorafenib, SSR-244738; Taribavirin hydrochloride, Taxus, Teduglutide, Tegaserod maleate, Telaprevir, Telbivudine, Tenofovir disoproxil fumarate, Tigecycline, Tiotropium bromide, Trabectedin, Travoprost

  20. Preparation of ultrathin, robust protein microcapsules through template-mediated interfacial reaction between amine and catechol groups.

    PubMed

    Wang, Xiaoli; Shi, Jiafu; Jiang, Zhongyi; Li, Zheng; Zhang, Wenyan; Song, Xiaokai; Ai, Qinghong; Wu, Hong

    2013-11-11

    A novel approach to the synthesis of protein microcapsules is developed through template-mediated interfacial reaction. Protein-doped CaCO3 templates are first synthetized via coprecipitation and then coated with a catechol-containing alginate (AlgDA) layer. Afterward, the templates are exposed to ethylenediamine tetraacetic acid disodium (EDTA) solution to dissolve CaCO3. During CaCO3 dissolution, the generated CO2 gas pushes protein molecules moving to the AlgDA layer, and thereby Michael addition and Schiff base reactions proceed, forming the shell of protein microcapsules. Three kinds of proteins, namely, bovine serum albumin, catalase, and protamine sulfate, are utilized. The shell thickness of microcapsule varies from 25 to 82 nm as the doping amount of protein increased from 2 to 6 mg per 66 mg CaCO3. The protein microcapsules have a robust but flexible shell and can be reversibly deformed upon exposure to osmotic pressure. The bioactivity of protein microcapsules is demonstrated through enzymatic catalysis experiments. The protein microcapsules remain about 80% enzymatic activity of the equivalent free protein. Hopefully, our approach could be extended to many other applications such as drug/gene delivery, tissue scaffolds, and catalysis due to the universality of Michael reaction and Schiff base reactions.