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Sample records for agents mycophenolic acid

  1. Mycophenolic acid agents: is enteric coating the answer?

    Directory of Open Access Journals (Sweden)

    Manitpisitkul W

    2011-03-01

    Full Text Available Wana Manitpisitkul1, Sabrina Lee2, Matthew Cooper31Department of Pharmacy, University of Maryland Medical Center, Baltimore, MD, USA; 2Solid Organ Transplant Program, University of Utah Health Care, Salt Lake City, UT, USA; 3Department of Surgery, University of Maryland School of Medicine, Baltimore, MD, USAAbstract: Addition of mycophenolate mofetil (MMF to calcineurin-based immunosuppressive therapy has led to a significant improvement in graft survival and reduction of acute rejection in renal transplant recipients. However, in clinical practice, MMF dose reduction, interruption, or discontinuation due to hematological and gastrointestinal (GI side-effects occurred in up to 50% of the patients. Large retrospective analyses have demonstrated that patients requiring MMF dose manipulation due to adverse events experienced a higher rate of rejection and graft loss. Enteric-coated mycophenolate sodium (EC-MPS was developed with the goal of improving upper GI side-effects. Here, we review the efficacy and safety of EC-MPS in de novo kidney transplant recipient, and in stable renal transplant patients who were converted from MMF. The changes in GI-related adverse events using patient-reported outcome instruments are also reviewed.Keywords: enteric-coated mycophenolate sodium, mycophenolate mofetil, kidney transplant, efficacy, gastrointestinal tolerability

  2. Evaluation of potential interactions between mycophenolic acid derivatives and proton pump inhibitors.

    Science.gov (United States)

    Gabardi, Steven; Olyaei, Ali

    2012-01-01

    To evaluate the incidence of gastrointestinal (GI) complications in solid organ transplant (SOT) recipients, impact of the complications on transplant outcomes, and the potential interactions between mycophenolic acid (MPA) derivatives and proton pump inhibitors (PPIs). An unrestricted literature search (1980-January 2012) was performed with MEDLINE and EMBASE using the following key words: drug-drug interaction, enteric-coated mycophenolic acid, GI complications, mycophenolate mofetil, solid organ transplant, and proton pump inhibitor, including individual agents within the class. Abstracts from scientific meetings were also evaluated. Additionally, reference citations from identified publications were reviewed. Relevant English-language, original research articles and review articles were evaluated if they focused on any of the topics identified in the search or included substantial content addressing GI complications in SOT recipients or drug interactions. GI complications are frequent among SOT recipients, with some studies showing prevalence rates as high as 70%. Transplant outcomes among renal transplant recipients are significantly impacted by GI complications, especially in patients requiring immunosuppressant dosage reductions or premature discontinuation. To this end, PPI use among patients receiving transplants is common. Recent data demonstrate that PPIs significantly reduce the overall exposure to MPA after oral administration of mycophenolate mofetil. Similar studies show this interaction does not exist between PPIs and enteric-coated mycophenolic acid (EC-MPA). Unfortunately, most of the available data evaluating this interaction are pharmacokinetic analyses that do not investigate the clinical impact of this interaction. A significant interaction exists between PPIs and mycophenolate mofetil secondary to reduced dissolution of mycophenolate mofetil in higher pH environments. EC-MPA is not absorbed in the stomach; therefore, low intragastric acidity

  3. Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome

    Science.gov (United States)

    Tellier, Stéphanie; Dallocchio, Aymeric; Guigonis, Vincent; Saint-Marcoux, Frank; Llanas, Brigitte; Ichay, Lydia; Bandin, Flavio; Godron, Astrid; Morin, Denis; Brochard, Karine; Gandia, Peggy; Bouchet, Stéphane; Marquet, Pierre; Decramer, Stéphane

    2016-01-01

    Background and objectives Therapeutic drug monitoring of mycophenolic acid can improve clinical outcome in organ transplantation and lupus, but data are scarce in idiopathic nephrotic syndrome. The aim of our study was to investigate whether mycophenolic acid pharmacokinetics are associated with disease control in children receiving mycophenolate mofetil for the treatment of steroid–dependent nephrotic syndrome. Design, setting, participants, & measurements This was a retrospective multicenter study including 95 children with steroid–dependent nephrotic syndrome treated with mycophenolate mofetil with or without steroids. Area under the concentration-time curve of mycophenolic acid was determined in all children on the basis of sampling times at 20, 60, and 180 minutes postdose, using Bayesian estimation. The association between a threshold value of the area under the concentration-time curve of mycophenolic acid and the relapse rate was assessed using a negative binomial model. Results In total, 140 areas under the concentration-time curve of mycophenolic acid were analyzed. The findings indicate individual dose adaptation in 53 patients (38%) to achieve an area under the concentration-time curve target of 30–60 mg·h/L. In a multivariable negative binomial model including sex, age at disease onset, time to start of mycophenolate mofetil, previous immunomodulatory treatment, and concomitant prednisone dose, a level of area under the concentration-time curve of mycophenolic acid >45 mg·h/L was significantly associated with a lower relapse rate (rate ratio, 0.65; 95% confidence interval, 0.46 to 0.89; P=0.01). Conclusions Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of mycophenolate mofetil in steroid–dependent nephrotic syndrome. Additional prospective studies are warranted to determine the optimal target for area under the concentration-time curve of mycophenolic acid in this population. PMID:27445161

  4. Production of Mycophenolic Acid by Penicillium brevicompactum Using Solid State Fermentation.

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    Patel, Gopal; Patil, Mahesh D; Soni, Surbhi; Chisti, Yusuf; Banerjee, Uttam Chand

    2017-05-01

    Solid-state fermentation using the microfungus Penicillium brevicompactum for the production of mycophenolic acid is reported in this paper. Of the initial substrates tested (whole wheat, cracked wheat, long grain Basmati rice, and short grain Parmal rice), Parmal rice proved to be the best. Under initial conditions, using steamed Parmal rice with 80% (w/w) initial moisture content, a maximum mycophenolic acid concentration of 3.4 g/kg substrate was achieved in 12 days of fermentation at 25 °C. The above substrate was supplemented with the following additional nutrients (g/L packed substrate): glucose 40.0, peptone 54.0, KH 2 PO 4 8.0, MgSO4⋅7H 2 O 2.0, glycine 7.0, and methionine 1.65 (initial pH 5.0). A small amount of a specified trace element solution was also added. The final mycophenolic acid concentration was increased to nearly 4 g/kg substrate by replacing glucose with molasses. Replacing Parmal rice with rice bran as substrate further improved the mycophenolic acid production to nearly 4.5 g/kg substrate.

  5. Pharmacokinetic study of mycophenolic acid in Iranian kidney transplant patients

    Directory of Open Access Journals (Sweden)

    Saeed Rezaee

    2013-02-01

    Full Text Available Background: The purpose of this study was to characterize the pharmacokinetic parameters of mycophenolic acid (MPA in Iranian kidney transplant patients. Methods: Plasma MPA concentration of mycophenolate mofetile (MMF 1 gram two times a day was measured in 21 Iranian kidney transplant recipients receiving treatment. Patients who entered the study had been transplanted for more than 3 months and their drug level was supposed to be at steady state. MMF concentration was measured with high-performance liquid chromatography (HPLC. Results: The plasma MPA concentration-time curve was characterized by an early sharp peak at about 1 hour postdose. The mean Area Under Curve (AUC, Cmax and Tmax were 47.0±18.3 µg.h/ml, 18.6±8.5 µg/ml and 1.0±0.5 hours respectively. Conclusion: The plasma MPA concentration-time curve pattern of Iranian patients was similar and consistent with previously reported profiles in other populations taking the same dose. Keywords: Mycophenolate mofetil, Mycophenolic acid, Pharmacokinetics, Area Under Curve, Kidney transplantation

  6. Limited sampling strategies drawn within 3 hours postdose poorly predict mycophenolic acid area-under-the-curve after enteric-coated mycophenolate sodium.

    NARCIS (Netherlands)

    Winter, B.C. de; Gelder, T. van; Mathôt, R.A.A.; Glander, P.; Tedesco-Silva, H.; Hilbrands, L.B.; Budde, K.; Hest, R.M. van

    2009-01-01

    Previous studies predicted that limited sampling strategies (LSS) for estimation of mycophenolic acid (MPA) area-under-the-curve (AUC(0-12)) after ingestion of enteric-coated mycophenolate sodium (EC-MPS) using a clinically feasible sampling scheme may have poor predictive performance. Failure of

  7. Enteric-coated mycophenolate sodium.

    Science.gov (United States)

    Gabardi, Steven; Tran, Jennifer L; Clarkson, Michael R

    2003-11-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium. Primary literature was obtained via a MEDLINE search (1966-June 2003). Abstracts were obtained from the manufacturer and included in the analysis. All studies and abstracts evaluating mycophenolate sodium in solid organ transplantation were considered for inclusion. English-language studies and abstracts were selected for inclusion, but were limited to those consisting of human subjects. Mycophenolate sodium, a mycophenolic acid prodrug, is an inhibitor of T-lymphocyte proliferation. Mycophenolic acid reduces the incidence of acute rejection in renal transplantation. Mycophenolate sodium is enteric coated and has been suggested as a potential method to reduce the gastrointestinal adverse events seen with mycophenolate mofetil. Both mycophenolate mofetil and mycophenolate sodium have been shown to be therapeutically equivalent at decreasing the incidence of allograft rejection and loss. The frequency of adverse events is similar between both compounds, with the most common events being diarrhea and leukopenia. Mycophenolate sodium is effective in preventing acute rejection in renal transplant recipients. At doses of 720 mg twice daily, the efficacy and safety profiles are similar to those of mycophenolate mofetil 1000 mg twice daily. Mycophenolate sodium has been approved in Switzerland; approval in the US is pending.

  8. Predicting the usefulness of therapeutic drug monitoring of mycophenolic acid: a computer simulation

    NARCIS (Netherlands)

    van Hest, Reinier; Mathot, Ron; Vulto, Arnold; Weimar, Willem; van Gelder, Teun

    2005-01-01

    The usefulness of therapeutic drug monitoring (TDM) of mycophenolate mofetil (MMF) was investigated with a computer simulation model. For a fixed-dose (FD) and a concentration-controlled (CC) MMF dosing regimen exposure to mycophenolic acid (MPA) was compared. A nonlinear mixed-effects model

  9. Mycophenolic acid AUC in Thai kidney transplant recipients receiving low dose mycophenolate and its association with UGT2B7 polymorphisms.

    Science.gov (United States)

    Pithukpakorn, Manop; Tiwawanwong, Tiwat; Lalerd, Yupaporn; Assawamakin, Anunchai; Premasathian, Nalinee; Tasanarong, Adis; Thongnoppakhun, Wanna; Vongwiwatana, Attapong

    2014-01-01

    Despite use of a lower mycophenolate dose in Thai kidney transplant patients, acceptable graft and patient outcomes can be achieved. We therefore examined the pharmacokinetics of mycophenolic acid (MPA) by area under the curve (AUC) and investigated genetic contribution in mycophenolate metabolism in this population. Kidney transplant recipients with stable graft function who were receiving mycophenolate mofetil 1,000 mg/d in combination with either cyclosporine or tacrolimus, and prednisolone were studied. The MPA concentration was measured by fluorescence polarization immunoassay (FPIA), at predose and 1, 1.5, 2, 4, 6, 8, 10, and 12 hours after dosing. Genetic polymorphisms in UGT1A8, UGT1A9, and UGT2B7 were examined by denaturing high-performance liquid chromatography (DHPLC)-based single-base extension (SBE) analysis. A total 138 patients were included in study. The mean AUC was 39.49 mg-h/L (28.39-89.58 mg-h/L), which was in the therapeutic range. The correlation between the predose MPA concentration and AUC was poor. The mean AUC in the tacrolimus group was higher than that in the cyclosporine group. Polymorphisms in UGT2B7 showed significant association with AUC. Most of our patients with reduced mycophenolate dose had the AUC within the therapeutic range. Genetic polymorphisms in UGT2B7 may play a role in MPA metabolism in Thai kidney transplant patients.

  10. Anti-Rhodotorula activity of mycophenolic acid enhanced in the presence of polyene antibiotic nystatin.

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    Kinoshita, H; Wongsuntornpoj, S; Ihara, F; Nihira, T

    2017-02-01

    Rhodotorula species are opportunistic pathogens, which cause not only systemic fungaemia but also other localized infections. Despite serious side effects such as nephrotoxicity and hypokalemia, amphotericin B (a polyene antifungal) has been commonly prescribed for Rhodotorula infection because Rhodotorula species are resistant against a candin family of antifungal agents. In this study, novel active compounds against Rhodotorula species were screened from the extracts of entomopathogenic fungi based on the synergistic effect of polyene nystatin (NYS), which causes efficient targeting of compounds due to increased permeability through the fungal cell membrane. Around 37% of culture extracts from 31 entomopathogenic fungal strains showed anti-Rhodotorula activity in the synergistic bioassay system, suggesting that the coexistence assay with NYS enhanced the discovery of anti-Rhodotorula compounds. Judging from various physicochemical data, the active component from strain HF763 was identified as an immunosuppressant drug, mycophenolic acid (MPA). The minimum inhibitory concentration of MPA against three pathogenic Rhodotorula strains was determined, focusing on the synergistic effect with NYS. The results revealed that the values decreased by at least 87% in the presence of NYS, indicating that MPA showed a synergistic effect with NYS. This study aimed to screen active compounds against Rhodotorula species that are resistant to a candin family of antifungal agents, from entomopathogenic fungi. Assuming that most of the latent antifungal compounds do not exert their activity due to their inability to penetrate the membrane, we took advantage of polyene nystatin in the screening to increase permeability through the fungal cell membrane. The result of the screening revealed hidden antifungal activity of mycophenolic acid, demonstrating that the method applied in this study unlocks the potentials of bioresources, and proposes a new remedy for mycosis. © 2016 The

  11. Risk evaluation and mitigation strategies: a focus on the mycophenolic acid preparations.

    Science.gov (United States)

    Rostas, Sara; Kim, Miae; Gabardi, Steven

    2014-03-01

    To review risks associated with mycophenolic acid (MPA) preparations and evaluate their required risk evaluation and mitigation strategies (REMS) elements. Articles were identified through a non-date-limited MEDLINE and EMBASE search using the terms fetal toxicity, teratogenicity, risk evaluation and mitigation strategies, REMS, MPA, mycophenolate mofetil, entericcoated MPA, and organ transplant. Information from the Food and Drug Administration (FDA) and the manufacturers of the MPA preparations was also evaluated. The MPA preparations are associated with several potential risks, including gastrointestinal disturbances and myelosuppression; however, their impact on the fetus in pregnant patients taking 1 of these agents poses the greatest risk. The FDA approved REMS programs for all MPA products, both innovator and generic preparations, in September 2012. With evidence of increased risk of miscarriage and birth defects associated with MPA use, the FDA instituted a REMS program that contains both a medication guide and elements to assure safe use (ETASU). The medication guides for the MPA products, which were previously FDA approved, should continue to be distributed to patients who get either an initial prescription filled or a refill. The ETASU requires prescribers to complete training and obtain patient signatures on the Patient-Prescriber Acknowledgment Form. A single, national, voluntary pregnancy registry specific to this medication has been established, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA.

  12. Consensus report on therapeutic drug monitoring of mycophenolic acid in solid organ transplantation

    NARCIS (Netherlands)

    D. Kuypers (Dirk); Y. le Meur (Yann); M. Cantarovich (Marcelo); M.J. Tredger (Michael); S.E. Tett (Susan); D. Cattaneo (Dario); B. Tönshoff (Burkhard); D.W. Holt (David); J. Chapman (Jeremy); T. van Gelder (Teun)

    2010-01-01

    textabstractWith the increasing use of mycophenolic acid (MPA) in solid organ transplantation, the need for more accurate drug dosing has become evident. Personalized immunosuppressive therapy requires better strategies for avoidance of drug-related toxicity while maintaining efficacy. Few studies

  13. A longitudinal assessment of adherence with immunosuppressive therapy following kidney transplantation from the Mycophenolic Acid Observational REnal Transplant (MORE) study.

    Science.gov (United States)

    Tsapepas, Demetra; Langone, Anthony; Chan, Laurence; Wiland, Anne; McCague, Kevin; Chisholm-Burns, Marie

    2014-04-17

    Nonadherence with immunosuppressive therapy after renal transplantation is a major clinical concern, but longitudinal data are sparse. Adherence data were recorded during the Mycophenolic Acid Observational REnal Transplant (MORE) study to help inform compliance management decisions. Prospective data were analyzed from the four-year, observational MORE study of de novo adult renal transplant recipients receiving mycophenolic acid (MPA) as enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) at 40 US sites under routine management. Adherence was assessed using the Immunosuppressant Therapy Adherence Scale (ITAS): total score 0-12 (12, adherence; adherent recipients (p=0.59); graft loss was 4.7% (19/402) vs. 3.0% (12/406) (p=0.20); death was 1.5% (6/402) vs. 4.7% (19/406) (p=0.013). Adherence to the immunosuppressive regimen decreases over time, highlighting the need to monitor and encourage adherence even in long-term maintenance kidney transplant patients. Other than African American race, demographic factors may be of limited value in predicting nonadherence.

  14. Simultaneous determination of ochratoxin A, mycophenolic acid and fumonisin B-2 in meat products

    DEFF Research Database (Denmark)

    Sørensen, Louise Marie; Mogensen, Jesper; Nielsen, Kristian Fog

    2010-01-01

    Here we present a method for simultaneous determination of the fungal metabolites mycophenolic acid, ochratoxin A (OTA) and fumonisin B-2 (FB2) in meat products. Extraction was performed with water-acetonitrile, followed by acetone-induced precipitation of salts and proteins. Purification...

  15. Do cytostatic drugs reach drinking water? The case of mycophenolic acid

    International Nuclear Information System (INIS)

    Franquet-Griell, Helena; Ventura, Francesc; Boleda, M.Rosa; Lacorte, Silvia

    2016-01-01

    Mycophenolic acid (MPA) has been identified as a new river contaminant according to its wide use and high predicted concentration. The aim of this study was to monitor the impact of MPA in a drinking water treatment plant (DWTP) that collects water downstream Llobregat River (NE Spain) in a highly densified urban area. During a one week survey MPA was recurrently detected in the DWTP intake (17–56.2 ng L"−"1). The presence of this compound in river water was associated to its widespread consumption (>2 tons in 2012 in Catalonia), high excretion rates and low degradability. The fate of MPA in waters at each treatment step of the DWTP was analyzed and complete removal was observed after pretreatment with chlorine dioxide. So far, MPA has not been described as water contaminant and its presence associated with its consumption in anticancer treatments is of relevance to highlight the importance of monitoring this compound. - Highlights: • MPA, a cytostatic drug, has been identified as a new river water contaminant. • MPA is eliminated during dioxychlorination in a drinking water treatment plant. • No residues of MPA were detected in finished drinking water. • Isotope dilution LC-MS/MS permitted the trace quantification of MPA in water. - Mycophenolic acid, a cytostatic drug, has been identified as a new river water contaminant and it is removed during purification in a Drinking Water Treatment Plant.

  16. [Duodenal villous atrophy associated with Mycophenolate mofetil: report of one case].

    Science.gov (United States)

    Tapia, Oscar; Villaseca, Miguel; Sierralta, Armando; Roa, Juan Carlos

    2010-05-01

    Mycophenolate mofetil (MMF) is an immunosupressor agent frequently used in patients after bone marrow or solid organ transplants. The most common adverse reactions of the drug are gastrointestinal, specially diarrhea and vomiting. We report a 53-year-old male, that received a heart transplant receiving immunosuppression with cyclosporine, mycophenolate mofetil and prednisone. Six months after the transplant, the patient started with diarrhea, anorexia and weight loss. A duodenal biopsy showed villous atrophy. Celiac disease and the presence of parasites were discarded. Mycophenolate mofetil was discontinued and one week later, diarrhea subsided. Two months later the patient was asymptomatic and recovered weight. A new duodenal biopsy showed absence of villous atrophy.

  17. Pharmacodynamic Monitoring of Inosine Monophosphate Dehydrogenase Activity: A Basis For Optimized and Individualized Mycophenolate Mofetil Therapy

    NARCIS (Netherlands)

    F. Sombogaard (Ferdi)

    2010-01-01

    textabstractIn 1896 Gosic isolated for the first time mycophenolic acid (MPA) from Penicillium glaucum.It was subsequently isolated from Penicillium stoloniferum Thom (synonym P. brevi-compactum Dierckx) by Alsberg and Black in 1913 who gave the acid phenolic substance its name mycophenolic acid

  18. Exposure to Mycophenolate and Fatherhood.

    Science.gov (United States)

    Midtvedt, Karsten; Bergan, Stein; Reisæter, Anna Varberg; Vikse, Bjørn Egil; Åsberg, Anders

    2017-07-01

    Mycophenolic acid (MPA) is the active immunosuppressive substance in both mycophenolate mofetil and mycophenolate sodium, and it is widely used after organ transplantation. In women, taking MPA is teratogenic and may also influence spermatogenesis. There is a lack of knowledge regarding outcome of pregnancies fathered by men exposed to MPA. We compared outcomes in pregnancies fathered by renal transplant men per whether they had been exposed to MPA or not at time of conception. A nationwide population-based retrospective cohort study was performed. Data from the Norwegian Renal Registry with all renal transplanted men alive between January 1, 1995 and December 31, 2015 were included, and relevant outcome data were extracted from the Medical Birth Registry of Norway. During the given time, 230 immunosuppressed renal transplanted men fathered 350 children (155 on MPA/195 not on MPA). There were no significant increased risks of malformation (3.9% vs. 2.6%, P = 0.49) in MPA exposed versus unexposed cohorts of children. The average dose (±SD) of mycophenolate was 1.42 ± 0.3 g/day and the individual median MPA trough concentration in the time period of anticipated conception and pregnancy was 2.8 ± 1.6 mg/L. Birth weight was similar in exposed and unexposed cohorts of children; 3381 ± 681 g vs. 3429 ± 714 g (P = 0.53). Paternal exposure to MPA did not increase the risk of adverse birth outcomes in children fathered by male kidney transplanted patients. These results are reassuring and support the continuation of paternal MPA treatment before, during, and after conception.

  19. Successful Treatment of Fibrosing Organising Pneumonia Causing Respiratory Failure with Mycophenolic Acid.

    Science.gov (United States)

    Paul, Christina; Lin-Shaw, Ammy; Joseph, Mariamma; Kwan, Keith; Sergiacomi, Gianluigi; Mura, Marco

    2016-01-01

    Organising pneumonia (OP) is usually promptly responsive to corticosteroid treatment. We describe a series of 3 cases of severe, progressive, biopsy-proven fibrosing OP causing respiratory failure. All cases presented with peribronchial and subpleural consolidations, had a fibro-inflammatory infiltrative component in the alveolar septa, and only had a partial and unsatisfactory response to corticosteroids. However, they responded to mycophenolic acid (MPA) treatment with resolution of respiratory failure as well as clinical and functional improvement. MPA as an additional treatment option for aggressive forms of fibrosing OP and interstitial lung disease needs to be further explored. © 2016 S. Karger AG, Basel.

  20. The necrotic signal induced by mycophenolic acid overcomes apoptosis-resistance in tumor cells.

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    Gwendaline Guidicelli

    Full Text Available BACKGROUND: The amount of inosine monophosphate dehydrogenase (IMPDH, a pivotal enzyme for the biosynthesis of the guanosine tri-phosphate (GTP, is frequently increased in tumor cells. The anti-viral agent ribavirin and the immunosuppressant mycophenolic acid (MPA are potent inhibitors of IMPDH. We recently showed that IMPDH inhibition led to a necrotic signal requiring the activation of Cdc42. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we strengthened the essential role played by this small GTPase in the necrotic signal by silencing Cdc42 and by the ectopic expression of a constitutive active mutant of Cdc42. Since resistance to apoptosis is an essential step for the tumorigenesis process, we next examined the effect of the MPA-mediated necrotic signal on different tumor cells demonstrating various mechanisms of resistance to apoptosis (Bcl2-, HSP70-, Lyn-, BCR-ABL-overexpressing cells. All tested cells remained sensitive to MPA-mediated necrotic signal. Furthermore, inhibition of IMPDH activity in Chronic Lymphocytic Leukemia cells was significantly more efficient at eliminating malignant cells than apoptotic inducers. CONCLUSIONS/SIGNIFICANCE: These findings indicate that necrosis and apoptosis are split signals that share few if any common hub of signaling. In addition, the necrotic signaling pathway induced by depletion of the cellular amount of GTP/GDP would be of great interest to eliminate apoptotic-resistant tumor cells.

  1. Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease

    NARCIS (Netherlands)

    de Winter, Brenda C. M.; Neumann, Irmgard; van Hest, Reinier M.; van Gelder, Teun; Mathot, Ron A. A.

    2009-01-01

    Mycophenolate mofetil (MMF) is increasingly used for the treatment of autoimmune diseases (AID). In renal transplant recipients, it has been demonstrated that adjustment of the MMF dose according to the area under the plasma concentration versus time curve (AUC) of mycophenolic acid (MPA), the

  2. A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids

    DEFF Research Database (Denmark)

    Syed, Muzeeb; Srinivas, Nuggehally R

    2016-01-01

    Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the an...

  3. Do cytostatic drugs reach drinking water? The case of mycophenolic acid.

    Science.gov (United States)

    Franquet-Griell, Helena; Ventura, Francesc; Boleda, M Rosa; Lacorte, Silvia

    2016-01-01

    Mycophenolic acid (MPA) has been identified as a new river contaminant according to its wide use and high predicted concentration. The aim of this study was to monitor the impact of MPA in a drinking water treatment plant (DWTP) that collects water downstream Llobregat River (NE Spain) in a highly densified urban area. During a one week survey MPA was recurrently detected in the DWTP intake (17-56.2 ng L(-1)). The presence of this compound in river water was associated to its widespread consumption (>2 tons in 2012 in Catalonia), high excretion rates and low degradability. The fate of MPA in waters at each treatment step of the DWTP was analyzed and complete removal was observed after pretreatment with chlorine dioxide. So far, MPA has not been described as water contaminant and its presence associated with its consumption in anticancer treatments is of relevance to highlight the importance of monitoring this compound. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Future immunosuppressive agents in solid-organ transplantation.

    Science.gov (United States)

    Gabardi, Steven; Cerio, Jeffrey

    2004-06-01

    To review the pharmacology, pharmacokinetics, efficacy, and safety of mycophenolate sodium, everolimus, and FTY720. Clinical trials and abstracts evaluating mycophenolate sodium, everolimus, and FTY720 in solid-organ transplantation were considered for evaluation. English-language studies and published abstracts were selected for inclusion. Mycophenolate sodium has recently been approved by the Food and Drug Adminstration for marketing in the United States; everolimus and FTY720 are immunosuppressive agents that may soon be available in the United States. These agents have proven efficacy in reducing the incidence of acute rejection in solid-organ transplantation. Clinical trials have shown that these newer agents are relatively well tolerated. The most common adverse events associated with these agents were gastrointestinal and hematologic effects (mycophenolate sodium); hyperlipidemia, increased serum creatinine, and hematologic effects (everolimus): and gastrointestinal effects, headache, and bradycardia (FTY720). Mycophenolate sodium has been approved in some European countries and the United States. Everolimus has been approved in some European countries and a new drug application has been submitted to the Food and Drug Administration. FTY720 is currently in phase III clinical trials and submission to the Food and Drug Administration for approval is a few years away. The approval of these agents will furnish the transplant practitioner with even more options for immunosuppression.

  5. Determination of mycophenolic acid in mest products using mixed mode reversed phase-anion exchange clean-up and liquid chromatography-high-resolution mass spectrometry

    DEFF Research Database (Denmark)

    Sørensen, Louise Marie; Nielsen, Kristian Fog; Jacobsen, Thomas

    2008-01-01

    A method for determination of mycophenolic acid (MPA) in dry-cured ham, fermented sausage and liver pate is described. MPA was extracted from meat with bicarbonate-acetonitrile, further cleaned-up by mixed mode reversed phase-anion exchange and detected using a LC-MS system with electrospray...

  6. Mycophenolic acid inhibits migration and invasion of gastric cancer cells via multiple molecular pathways.

    Directory of Open Access Journals (Sweden)

    Boying Dun

    Full Text Available Mycophenolic acid (MPA is the metabolized product and active element of mycophenolate mofetil (MMF that has been widely used for the prevention of acute graft rejection. MPA potently inhibits inosine monophosphate dehydrogenase (IMPDH that is up-regulated in many tumors and MPA is known to inhibit cancer cell proliferation as well as fibroblast and endothelial cell migration. In this study, we demonstrated for the first time MPA's antimigratory and anti-invasion abilities of MPA-sensitive AGS (gastric cancer cells. Genome-wide expression analyses using Illumina whole genome microarrays identified 50 genes with ≥2 fold changes and 15 genes with > 4 fold alterations and multiple molecular pathways implicated in cell migration. Real-time RT-PCR analyses of selected genes also confirmed the expression differences. Furthermore, targeted proteomic analyses identified several proteins altered by MPA treatment. Our results indicate that MPA modulates gastric cancer cell migration through down-regulation of a large number of genes (PRKCA, DOCK1, INF2, HSPA5, LRP8 and PDGFRA and proteins (PRKCA, AKT, SRC, CD147 and MMP1 with promigratory functions as well as up-regulation of a number of genes with antimigratory functions (ATF3, SMAD3, CITED2 and CEAMCAM1. However, a few genes that may promote migration (CYR61 and NOS3 were up-regulated. Therefore, MPA's overall antimigratory role on cancer cells reflects a balance between promigratory and antimigratory signals influenced by MPA treatment.

  7. A combined photophysical and computational study on the binding of mycophenolate mofetil and its major metabolite to transport proteins.

    Science.gov (United States)

    Vendrell-Criado, Victoria; González-Bello, Concepción; Miranda, Miguel A; Jiménez, M Consuelo

    2018-06-15

    Binding of the immunosuppressive agent mycophenolate mofetil (MMP) and its pharmacologically active metabolite mycophenolic acid (MPA) to human serum albumin (HSA) and α 1 -acid glycoprotein (HAAG) has been investigated by means of an integrated approach involving selective excitation of the drug fluorophore, following their UV-A triggered fluorescence and docking studies. The formation of the protein/ligand complexes was evidenced by a dramatic enhancement of the fluorescence intensity and a hypsochromic shift of the emission band. In HSA, competitive studies using oleic acid as site I probe revealed site I as the main binding site of the ligands. Binding constants revealed that the affinity of the active metabolite by HSA is four-fold higher than its proactive form. Moreover, the affinity of MMP by HSA is three-fold higher than by HAAG. Docking studies revealed significant molecular binding differences in the binding of MMP and MPA to sub-domain IIA of HSA (site 1). For MPA, the aromatic moiety would be in close contact to Trp214 with the flexible chain pointing to the other end of the sub-domain; on the contrary, for MMP, the carboxylate group of the chain would be fixed nearby Trp214 through electrostatic interactions with residues Arg218 and Arg222. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. "Determination of mycophenolic acid in human plasma by high-performance liquid chromatography"

    Directory of Open Access Journals (Sweden)

    "Mehdi Ahadi Barzoki

    2005-05-01

    Full Text Available A simple, sensitive and reproducible HPLC method is presented for determination of mycophenolic acid(MPA in human plasma. Samples were prepared after precipitation of the plasma protein by addition of acetonitrile and naproxen was used as internal standard (I.S.. Separation was performed by reversedphase HPLC, using a Hamilton PRP-C18 Column, 51% acetonitrile and 49% potassium phosphate buffer (20 mM at pH 3.0 as mobile phase, flow rate of 1.0 ml/min, and UV detection at 215 nm. MPA and I.S. had retention times of 7.5 and 11.35 min, respectively. The method showed an acceptable linearity in the range of 0.1µg/ml-40µg/ml with r2 of .9992. The concentration of 0.1µg/ml was determined as quantification limit. Mean absolute recovery was 94.8%. The mean intra- and inter-day reproducibility of method was 4.6 and 11.4% respectively.

  9. Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

    International Nuclear Information System (INIS)

    Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

    2006-01-01

    Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH

  10. Simultaneous determination of mycophenolate mofetil and its active metabolite, mycophenolic acid, by differential pulse voltammetry using multi-walled carbon nanotubes modified glassy carbon electrode

    Energy Technology Data Exchange (ETDEWEB)

    Madrakian, Tayyebeh, E-mail: madrakian@basu.ac.ir; Soleimani, Mohammad; Afkhami, Abbas

    2014-09-01

    A highly sensitive electrochemical sensor for the simultaneous determination of mycophenolate mofetil (MPM) and mycophenolic acid (MPA) was fabricated by multi-walled carbon nanotubes modified glassy carbon electrode (MWCNTs/GCE). The electrochemical behavior of these two drugs was studied at the modified electrode using cyclic voltammetry and adsorptive differential pulse voltammetry. MPM and MPA were oxidized at the GCE during an irreversible process. DPV analysis showed two oxidation peaks at 0.87 V and 1.1 V vs. Ag/AgCl for MPM and an oxidation peak at 0.87 V vs. Ag/AgCl for MPA in phosphate buffer solution of pH 5.0. The MWCNTs/GCE displayed excellent electrochemical activities toward oxidation of MPM and MPA relative to the bare GCE. The experimental design algorithm was used for optimization of DPV parameters. The electrode represents linear responses in the range 5.0 × 10{sup −6} to 1.6 × 10{sup −4} mol L{sup −1} and 2.5 × 10{sup −6} mol L{sup −1} to 6.0 × 10{sup −5} mol L{sup −1} for MPM and MPA, respectively. The detection limit was found to be 9.0 × 10{sup −7} mol L{sup −1} and 4.0 × 10{sup −7} mol L{sup −1} for MPM and MPA, respectively. The modified electrode showed a good sensitivity and stability. It was successfully applied to the simultaneous determination of MPM and MPA in plasma and urine samples. - Highlights: • A new modified electrochemical sensor was constructed and used. • Multiwalled carbon nanotubes were used as the modifiers. • MPM and MPA were measured simultaneously at the low levels. • The sensor was used to the determination of MPA and MPM in real samples.

  11. Impact of dose reductions on efficacy outcome in heart transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil at 12 months post-transplantation.

    Science.gov (United States)

    Segovia, Javier; Gerosa, Gino; Almenar, Luis; Livi, Ugolino; Viganò, Mario; Arizón, Jose Maria; Yonan, Nizar; Di Salvo, Thomas G; Renlund, Dale G; Kobashigawa, Jon A

    2008-01-01

    Mycophenolic acid (MPA) dose reduction is associated with increased risk of rejection and graft loss in renal transplantation. This analysis investigated the impact of MPA dose changes with enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) in de novo heart transplant recipients. In a 12-month, single-blind trial, 154 patients (EC-MPS, 78; MMF, 76) were randomized to either EC-MPS (1080 mg bid) or MMF (1500 mg bid) in combination with cyclosporine and steroids. The primary efficacy variable was the incidence of treatment failure, comprising a composite of biopsy-proven (BPAR) and treated acute rejection, graft loss or death. Significantly fewer patients receiving EC-MPS required > or =2 dose reductions than patients on MMF (26.9% vs. 42.1% of patients, p = 0.048). Accordingly, the average daily dose of EC-MPS as a percentage of the recommended dose was significantly higher than for MMF (88.4% vs. 79.0%, p = 0.016). Among patients requiring > or =1 dose reduction, the incidence of treated BPAR grade > or =3A was significantly lower with EC-MPS compared with MMF (23.4% vs. 44.0%, p = 0.032). These data suggest that EC-MPS-treated heart transplant patients are less likely to require multiple dose reductions than those on MMF which may be associated with a significantly lower risk of treated BPAR > or =3A.

  12. Diagnostic efficiency of truncated area under the curve from 0 to 2 h (AUC₀₋₂) of mycophenolic acid in kidney transplant recipients receiving mycophenolate mofetil and concomitant tacrolimus.

    Science.gov (United States)

    Lampón, Natalia; Tutor-Crespo, María J; Romero, Rafael; Tutor, José C

    2011-07-01

    Recently, the use of the truncated area under the curve from 0 to 2 h (AUC(0-2)) of mycophenolic acid (MPA) has been proposed for therapeutic monitoring in liver transplant recipients. The aim of our study was the evaluation of the clinical usefulness of truncated AUC(0-2) in kidney transplant patients. Plasma MPA was measured in samples taken before the morning dose of mycophenolate mofetil, and one-half and 2 h post-dose, completing 63 MPA concentration-time profiles from 40 adult kidney transplant recipients. The AUC from 0 to 12 h (AUC(0-12)) was calculated using the validated algorithm of Pawinski et al. The truncated AUC(0-2) was calculated using the linear trapezoidal rule, and extrapolated to 0-12 h (trapezoidal extrapolated AUC(0-12)) as previously described. Algorithm calculated and trapezoidal extrapolated AUC(0-12) values showed high correlation (r=0.995) and acceptable dispersion (ma68=0.71 μg·h/mL), median prediction error (6.6%) and median absolute prediction error (12.6%). The truncated AUC(0-2) had acceptable diagnostic efficiency (87%) in the classification of subtherapeutic, therapeutic or supratherapeutic values with respect to AUC(0-12). However, due to the high inter-individual variation of the drug absorption-rate, the dispersion between both pharmacokinetic variables (ma68=6.9 μg·h/mL) was unacceptable. The substantial dispersion between truncated AUC(0-2) and AUC(0-12) values may be a serious objection for the routine use of MPA AUC(0-2) in clinical practice.

  13. Comparative analysis the binding affinity of mycophenolic sodium and meprednisone with human serum albumin: Insight by NMR relaxation data and docking simulation.

    Science.gov (United States)

    Ma, Xiaoli; He, Jiawei; Yan, Jin; Wang, Qing; Li, Hui

    2016-03-25

    Mycophenolic sodium is an immunosuppressive agent that is always combined administration with corticosteroid in clinical practice. Considering the distribution and side-effect of the drug may change when co-administrated drug exist, this paper comparatively analyzed the binding ability of mycophenolic sodium and meprednisone toward human serum albumin by nuclear magnetic resonance relaxation data and docking simulation. The nuclear magnetic resonance approach was based on the analysis of proton selective and non-selective relaxation rate enhancement of the ligand in the absence and presence of macromolecules. The contribution of the bound ligand fraction to the observed relaxation rate in relation to protein concentration allowed the calculation of the affinity index. This approach allowed the comparison of the binding affinity of mycophenolic sodium and meprednisone. Molecular modeling was operated to simulate the binding model of ligand and albumin through Autodock 4.2.5. Competitive binding of mycophenolic sodium and meprednisone was further conducted through fluorescence spectroscopy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Mycophenolate fetal toxicity and risk evaluation and mitigation strategies.

    Science.gov (United States)

    Kim, M; Rostas, S; Gabardi, S

    2013-06-01

    The mycophenolic acid (MPA) preparations are one of the most commonly used immunosuppressants in the United States. However, these agents carry a black box warning regarding their use during pregnancy due to an association with increased risk of miscarriage and congenital defects. To ensure that the benefits of MPA outweigh the risks, the Food and Drug Administration (FDA) required all manufacturers of MPA products to propose risk evaluation and mitigation strategies (REMS). Four years after initially calling for proposals, the FDA approved a single shared REMS system in September 2012. The elements of the MPA REMS include a medication guide and elements to assure safe use (ETASU). The medication guide, which was previously FDA-approved in 2008, should continue to be distributed to patients, and the ETASU requires physicians to complete training and obtain patient signatures on the "Patient-Prescriber Acknowledgement Form." A single, national, voluntary pregnancy registry is available, and pregnant patients should be encouraged to participate. Although the impact of the MPA REMS on clinical practice is not clear, it is a step toward increasing the understanding of fetal risks with MPA products among patients and possibly practitioners. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Mycophenolic acid suppresses human pterygium and normal tenon fibroblast proliferation in vitro.

    Science.gov (United States)

    Amer, Radgonde; Rabinowich, Liane; Maftsir, Genia; Puxeddu, Ilaria; Levi-Schaffer, Francesca; Solomon, Abraham

    2010-10-01

    To investigate whether mycophenolic acid (MPA) exerts antifibrotic effects on pterygium fibroblasts (PFB) with and without stimulation with fibrogenic cytokines, and to compare the efficacy of MPA with mitomycin (MMC) and dexamethasone (DXM) on PFB and tenon fibroblasts (TFB). TFB and PFB were obtained from tissue explants during strabismus or pterygium surgery. Proliferation of subconfluent fibroblasts ± basic fibroblast growth factor (bFGF) (10 ng/ml) was assessed by using the (3H) thymidine-incorporation assay. Cell cultures were incubated with MPA, MMC or DXM. Apoptosis was evaluated by quantifying Annexin V and propidium iodide positive cells with flow cytometry. MPA showed a concentration-dependent inhibition of proliferation of PFB ± bFGF as well as TFB ± bFGF. The antiproliferative effect of MPA was comparable with that of MMC and DXM. Short exposure of PFB to MPA under profibrogenic conditions was significantly inhibitory. No apoptotic effect was found on TFB. MPA suppressed tenon and pterygium fibroblast proliferation in vitro under basal and profibrogenic conditions. It was comparable with MMC under long-term exposure, but MMC was more suppressive under short-term exposure. MPA may be safer than MMC due to a more specific mechanism of action and lack of cytotoxicity. Further investigation is warranted regarding MPA concentrations that will lead to a potent antiproliferative effect in vivo.

  16. Comparison of 3 estimation methods of mycophenolic acid AUC based on a limited sampling strategy in renal transplant patients.

    Science.gov (United States)

    Hulin, Anne; Blanchet, Benoît; Audard, Vincent; Barau, Caroline; Furlan, Valérie; Durrbach, Antoine; Taïeb, Fabrice; Lang, Philippe; Grimbert, Philippe; Tod, Michel

    2009-04-01

    A significant relationship between mycophenolic acid (MPA) area under the plasma concentration-time curve (AUC) and the risk for rejection has been reported. Based on 3 concentration measurements, 3 approaches have been proposed for the estimation of MPA AUC, involving either a multilinear regression approach model (MLRA) or a Bayesian estimation using either gamma absorption or zero-order absorption population models. The aim of the study was to compare the 3 approaches for the estimation of MPA AUC in 150 renal transplant patients treated with mycophenolate mofetil and tacrolimus. The population parameters were determined in 77 patients (learning study). The AUC estimation methods were compared in the learning population and in 73 patients from another center (validation study). In the latter study, the reference AUCs were estimated by the trapezoidal rule on 8 measurements. MPA concentrations were measured by liquid chromatography. The gamma absorption model gave the best fit. In the learning study, the AUCs estimated by both Bayesian methods were very similar, whereas the multilinear approach was highly correlated but yielded estimates about 20% lower than Bayesian methods. This resulted in dosing recommendations differing by 250 mg/12 h or more in 27% of cases. In the validation study, AUC estimates based on the Bayesian method with gamma absorption model and multilinear regression approach model were, respectively, 12% higher and 7% lower than the reference values. To conclude, the bicompartmental model with gamma absorption rate gave the best fit. The 3 AUC estimation methods are highly correlated but not concordant. For a given patient, the same estimation method should always be used.

  17. USE OF MYCOPHENOLATE MOPHETYL IN PATIENT WITH SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    S.I. Valiyeva,

    2006-01-01

    Full Text Available The article reports a case of highly active SLE and lupusbnephritis in a 15 years old boy, who was treated with mycophenolate mophetyl the case was notable for high activity and aggressive course of the disease with rapid development of renal unsufficiency, polyorganic unsufficiency and antiphospholipid syndrome. Although the patient received an appropriate active therapy, including synchronized therapy (consisting of timebrelated plasmopherresis and infusions of cyclophosphamide and metyl prednisolone, glucocorticoides, preparations improving blood circulation (pentoxyphillin, dipiridamol, heparine, intravenous immunoglobulins, the disease activity control was unsufficient. The administration of mycophenolate mophetyl has led to diminuition of the disease activity, which was registered at the end of the second week of treatment, and finally has reached a level of clinical and laboratoty remission of the disease.Key words: systemic lupus erythematosus, mycophenolate mophetyl, children, treatment.

  18. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    International Nuclear Information System (INIS)

    Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

    2011-01-01

    Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  19. Mycophenolate mofetil in erosive genital lichen planus: a case and review of the literature.

    Science.gov (United States)

    Deen, Kristyn; McMeniman, Erin

    2015-03-01

    Erosive genital lichen planus is a disabling, inflammatory mucocutaneous condition that can cause significant patient morbidity and loss of function. Treatment initially involves topical corticosteroids but some patients can have severe treatment-resistant courses requiring systemic immunosuppression. With potentially unfavorable adverse effect profiles and subsequent intolerance of these agents by patients, erosive lichen planus can ultimately be a challenging condition to treat effectively. We present a case of a 66-year-old woman with treatment-resistant erosive genital lichen planus who was successfully managed with mycophenolate mofetil. Although there is only weak evidence for this agent in this condition, its role in dermatology is growing due to its efficacy and advantageous adverse effect profile and should therefore be considered in patients with treatment-resistant erosive genital lichen planus. © 2015 Japanese Dermatological Association.

  20. Mycophenolate Mofetil Modulates Differentiation of Th1/Th2 and the Secretion of Cytokines in an Active Crohn's Disease Mouse Model.

    Science.gov (United States)

    Lv, Qing-Kang; Liu, Ju-Xiong; Li, Su-Nan; Gao, Ying-Jie; Lv, Yan; Xu, Zi-Peng; Huang, Bing-Xu; Xu, Shi-Yao; Yang, Dong-Xue; Zeng, Ya-Long; Liu, Dian-Feng; Wang, Wei

    2015-11-06

    Mycophenolate mofetil (MMF) is an alternative immunosuppressive agent that has been reported to be effective and well tolerated for the treatment of refractory inflammatory bowel disease (IBD). The aim of this study was to investigate the therapeutic effect of MMF on intestinal injury and tissue inflammation, which were caused by Crohn's disease (CD). Here, trinitrobenzene sulfonic acid-relapsing (TNBS) colitis was induced in mice; then, we measured the differentiation of Th1/Th2 cells in mouse splenocytes by flow cytometry and the secretion of cytokines in mice with TNBS-induced colitis by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay (RT-PCR/ELISA). The results show that MMF significantly inhibited mRNA expression of pro-inflammatory cytokines IFN-γ, TNF-α, IL-12, IL-6, and IL-1β in mice with TNBS-induced colitis; however, MMF did not inhibit the expression of IL-10 mRNA. Additionally, ELISA showed that the serum levels of IFN-γ, TNF-α, IL-12, IL-6, and IL-1β were down-regulated in a TNBS model of colitis. Flow cytometric analysis showed MMF markedly reduced the percentages of Th1 and Th2 splenocytes in the CD mouse model. Mycophenolic acid (MPA) also significantly decreased the percentages of splenic Th1 and Th2 cells in vitro. Furthermore, MMF treatment not only significantly ameliorated diarrhea, and loss of body weight but also abrogated the histopathologic severity and inflammatory response of inflammatory colitis, and increased the survival rate of TNBS-induced colitic mice. These results suggest that treatment with MMF may improve experimental colitis and induce inflammatory response remission of CD by down-regulation of pro-inflammatory cytokines via modulation of the differentiation of Th1/Th2 cells.

  1. A randomized clinical trial comparing methotrexate and mycophenolate mofetil for noninfectious uveitis.

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne T A; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-10-01

    To compare the relative effectiveness of methotrexate and mycophenolate mofetil for noninfectious intermediate uveitis, posterior uveitis, or panuveitis. Multicenter, block-randomized, observer-masked clinical trial. Eighty patients with noninfectious intermediate, posterior, or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Patients were randomized to receive 25 mg weekly oral methotrexate or 1 g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤10 mg of prednisone and ≤2 drops of prednisolone acetate 1% a day, and (3) no declaration of treatment failure because of intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (P = 0.09). Treatment failure from adverse events or tolerability was not different by treatment arm (P = 0.99). There were no differences between treatment groups in time to corticosteroid-sparing control of inflammation (P = 0.44), change in best spectacle-corrected visual acuity (P = 0.68), or resolution of macular edema (P = 0.31). There was no statistically significant difference in corticosteroid-sparing control of

  2. Managing Drug-Drug Interaction Between Ombitasvir, Paritaprevir/Ritonavir, Dasabuvir, and Mycophenolate Mofetil.

    Science.gov (United States)

    Lemaitre, Florian; Ben Ali, Zeineb; Tron, Camille; Jezequel, Caroline; Boglione-Kerrien, Christelle; Verdier, Marie-Clémence; Guyader, Dominique; Bellissant, Eric

    2017-08-01

    No drug-drug interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of drug-drug interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.

  3. Glutamic acid as anticancer agent: An overview

    OpenAIRE

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K.

    2013-01-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. I...

  4. A Randomized Clinical Trial Comparing Methotrexate and Mycophenolate Mofetil for Non-Infectious Uveitis

    Science.gov (United States)

    Rathinam, Sivakumar R; Babu, Manohar; Thundikandy, Radhika; Kanakath, Anuradha; Nardone, Natalie; Esterberg, Elizabeth; Lee, Salena M; Enanoria, Wayne TA; Porco, Travis C; Browne, Erica N; Weinrib, Rachel; Acharya, Nisha R

    2014-01-01

    Objective To compare the relative effectiveness of methotrexate and mycophenolate mofetil for non-infectious intermediate uveitis, posterior uveitis, or panuveitis. Design Multicenter, block-randomized, observer-masked clinical trial Participants Eighty patients with non-infectious intermediate, posterior or panuveitis requiring corticosteroid-sparing therapy at Aravind Eye Hospitals in Madurai and Coimbatore, India. Intervention Patients were randomized to receive 25mg weekly oral methotrexate or 1g twice daily oral mycophenolate mofetil and were monitored monthly for 6 months. Oral prednisone and topical corticosteroids were tapered. Main Outcome Measures Masked examiners assessed the primary outcome of treatment success, defined by achieving the following at 5 and 6 months: (1) ≤0.5+ anterior chamber cells, ≤0.5+ vitreous cells, ≤0.5+ vitreous haze and no active retinal/choroidal lesions in both eyes, (2) ≤ 10 mg of prednisone and ≤ 2 drops of prednisolone acetate 1% a day and (3) no declaration of treatment failure due to intolerability or safety. Additional outcomes included time to sustained corticosteroid-sparing control of inflammation, change in best spectacle-corrected visual acuity, resolution of macular edema, adverse events, subgroup analysis by anatomic location, and medication adherence. Results Forty-one patients were randomized to methotrexate and 39 to mycophenolate mofetil. A total of 67 patients (35 methotrexate, 32 mycophenolate mofetil) contributed to the primary outcome. Sixty-nine percent of patients achieved treatment success with methotrexate and 47% with mycophenolate mofetil (p=0.09). Treatment failure due to adverse events or tolerability was not significantly different by treatment arm (p=0.99). There were no statistically significant differences between treatment groups in time to corticosteroid-sparing control of inflammation (p=0.44), change in best spectacle-corrected visual acuity (p=0.68), and resolution of macular

  5. Glutamic acid as anticancer agent: An overview.

    Science.gov (United States)

    Dutta, Satyajit; Ray, Supratim; Nagarajan, K

    2013-10-01

    The objective of the article is to highlight various roles of glutamic acid like endogenic anticancer agent, conjugates to anticancer agents, and derivatives of glutamic acid as possible anticancer agents. Besides these emphases are given especially for two endogenous derivatives of glutamic acid such as glutamine and glutamate. Glutamine is a derivative of glutamic acid and is formed in the body from glutamic acid and ammonia in an energy requiring reaction catalyzed by glutamine synthase. It also possesses anticancer activity. So the transportation and metabolism of glutamine are also discussed for better understanding the role of glutamic acid. Glutamates are the carboxylate anions and salts of glutamic acid. Here the roles of various enzymes required for the metabolism of glutamates are also discussed.

  6. Mycophenolate mofetil after methotrexate failure or intolerance in the treatment of scleritis and uveitis.

    Science.gov (United States)

    Sobrin, Lucia; Christen, William; Foster, C Stephen

    2008-08-01

    To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate. Retrospective noncomparative case series. Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006. We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control. Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed. Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.

  7. Mycophenolate Mofetil in Combination with Steroids for Treatment of C3 Glomerulopathy: A Case Series.

    Science.gov (United States)

    Avasare, Rupali S; Canetta, Pietro A; Bomback, Andrew S; Marasa, Maddalena; Caliskan, Yasar; Ozluk, Yasemin; Li, Yifu; Gharavi, Ali G; Appel, Gerald B

    2018-03-07

    C3 glomerulopathy is a form of complement-mediated GN. Immunosuppressive therapy may be beneficial in the treatment of C3 glomerulopathy. Mycophenolate mofetil is an attractive treatment option given its role in the treatment of other complement-mediated diseases and the results of the Spanish Group for the Study of Glomerular Diseases C3 Study. Here, we study the outcomes of patients with C3 glomerulopathy treated with steroids and mycophenolate mofetil. We conducted a retrospective chart review of patients in the C3 glomerulopathy registry at Columbia University and identified patients treated with mycophenolate mofetil for at least 3 months and follow-up for at least 1 year. We studied clinical, histologic, and genetic data for the whole group and compared data for those who achieved complete or partial remission (responders) with those who did not achieve remission (nonresponders). We compared remission with mycophenolate mofetil with remission with other immunosuppressive regimens. We identified 30 patients who met inclusion criteria. Median age was 25 years old (interquartile range, 18-36), median creatinine was 1.07 mg/dl (interquartile range, 0.79-1.69), and median proteinuria was 3200 mg/g creatinine (interquartile range, 1720-6759). The median follow-up time was 32 months (interquartile range, 21-68). Twenty (67%) patients were classified as responders. There were no significant differences in baseline characteristics between responders and nonresponders, although initial proteinuria was lower (median 2468 mg/g creatinine) in responders compared with nonresponders (median 5000 mg/g creatinine) and soluble membrane attack complex levels were higher in responders compared with nonresponders. For those tapered off mycophenolate mofetil, relapse rate was 50%. Genome-wide analysis on complement genes was done, and in 12 patients, we found 18 variants predicted to be damaging. None of these variants were previously reported to be pathogenic. Mycophenolate

  8. Salicylic acid as a peeling agent: a comprehensive review

    Directory of Open Access Journals (Sweden)

    Arif T

    2015-08-01

    Full Text Available Tasleem Arif Postgraduate Department of Dermatology, STD and Leprosy, Government Medical College, Srinagar, Jammu and Kashmir, India Abstract: Salicylic acid has been used to treat various skin disorders for more than 2,000 years. The ability of salicylic acid to exfoliate the stratum corneum makes it a good agent for peeling. In particular, the comedolytic property of salicylic acid makes it a useful peeling agent for patients with acne. Once considered as a keratolytic agent, the role of salicylic acid as a desmolytic agent, because of its ability to disrupt cellular junctions rather than breaking or lysing intercellular keratin filaments, is now recognized and is discussed here. Salicylic acid as a peeling agent has a number of indications, including acne vulgaris, melasma, photodamage, freckles, and lentigines. The efficacy and safety of salicylic acid peeling in Fitzpatrick skin types I–III as well as in skin types V and VI have been well documented in the literature. This paper reviews the available data and literature on salicylic acid as a peeling agent and its possible indications. Its properties, efficacy and safety, the peeling procedure, and possible side effects are discussed in detail. An account of salicylism is also included. Keywords: acne vulgaris, desmolytic agent, melasma, photodamage, salicylic acid 

  9. Salicylic acid as a peeling agent: a comprehensive review.

    Science.gov (United States)

    Arif, Tasleem

    2015-01-01

    Salicylic acid has been used to treat various skin disorders for more than 2,000 years. The ability of salicylic acid to exfoliate the stratum corneum makes it a good agent for peeling. In particular, the comedolytic property of salicylic acid makes it a useful peeling agent for patients with acne. Once considered as a keratolytic agent, the role of salicylic acid as a desmolytic agent, because of its ability to disrupt cellular junctions rather than breaking or lysing intercellular keratin filaments, is now recognized and is discussed here. Salicylic acid as a peeling agent has a number of indications, including acne vulgaris, melasma, photodamage, freckles, and lentigines. The efficacy and safety of salicylic acid peeling in Fitzpatrick skin types I-III as well as in skin types V and VI have been well documented in the literature. This paper reviews the available data and literature on salicylic acid as a peeling agent and its possible indications. Its properties, efficacy and safety, the peeling procedure, and possible side effects are discussed in detail. An account of salicylism is also included.

  10. Determination of Mycophenolic acid in the vitreous humor using the HPLC-ESI-MS/MS method: application of intraocular pharmacokinetics study in rabbit eyes with ophthalmic implantable device.

    Science.gov (United States)

    Martins Duarte Byrro, Ricardo; de Oliveira Fulgêncio, Gustavo; Rocha Chellini, Paula; da Silva Cunha, Armando; Pianetti, Gerson Antônio

    2013-10-01

    Mycophenolic acid (MPA) is an immunosuppressive agent widely used in the treatment of solid organ transplant rejection. The success of MPA in the treatment of inflammatory intraocular diseases has been reported in recent literature. The treatment of inflammatory eye diseases in the posterior chamber is a challenge due to the anatomy of the eye, which presents certain barriers to drug access. Thus, the bioavailability of drugs in the eye is quite low, and successful drug delivery may well represent a key limiting factor to attaining a successful therapeutic strategy. Ophthalmic controlled drug delivery offers the potential to enhance the efficacy of treatment for pathological conditions. Thus, a novel delivery system based on a biodegradable polymeric device, which can be implanted inside the eye and deliver MPA directly to the target, is being developed. Specific analytical methods to determine the use of effective drugs within the eye are needed to characterize this device. A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the quantitation of MPA in the vitreous humor of rabbits was developed and validated. The vitreous was collected from rabbits, extracted by a protein precipitation extraction procedure and then separated on a C18 column with a mobile phase comprised of 0.15% aqueous acetic acid and methanol (60:40, v/v). The calibration curve was constructed within the range of 3-10,000 ng/mL for MPA. The mean R.S.D. values for the intra-run and inter-run precision were 5.15% and 4.35%. The mean accuracy value was 100.16%. The validated method was successfully applied to determine the MPA concentration in the vitreous humor of rabbits treated with an ocular implantable device. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Esophageal Cicatricial Pemphigoid as an Isolated Involvement Treated with Mycophenolate Mofetil

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    Sandra Sánchez Prudencio

    2015-01-01

    Full Text Available Cicatricial pemphigoid (CP is a rare blistering autoimmune disease. Esophageal involvement occurs in widespread disease and rarely appears as the only affected organ. We report a 67-year-old Caucasian female with esophageal dysphagia and weight loss. Several oral panendoscopies showed multiple exudative ulcerations with fibrin and webs in mid- and proximal esophagus and a peeling mucosa. There were no lesions in other organs. We established the diagnosis performing a direct immunofluorescence (DIF, demonstrating IgG3 and complement deposition along the basement membrane. As initial treatment the patient received prednisone 60 mg and 1 gr twice daily of mycophenolate mofetil (MMF as a steroid-sparing agent due to its lower toxicity and its selective mechanism of action. Six months later there was a significant clinical improvement and the esophageal ulcerations had disappeared, developing cicatricial fibrous rings, although no stenosis was present. Four years later, the patient remains asymptomatic with a low maintenance dose of MMF.

  12. Salicylic acid as a peeling agent: a comprehensive review

    OpenAIRE

    Arif, Tasleem

    2015-01-01

    Tasleem Arif Postgraduate Department of Dermatology, STD and Leprosy, Government Medical College, Srinagar, Jammu and Kashmir, India Abstract: Salicylic acid has been used to treat various skin disorders for more than 2,000 years. The ability of salicylic acid to exfoliate the stratum corneum makes it a good agent for peeling. In particular, the comedolytic property of salicylic acid makes it a useful peeling agent for patients with acne. Once considered as a keratolytic agent, the role of s...

  13. Do Asian renal transplant patients need another mycophenolate mofetil dose compared with Caucasian or African American patients?

    Science.gov (United States)

    Li, Pengmei; Shuker, Nauras; Hesselink, Dennis A; van Schaik, Ron H N; Zhang, Xianglin; van Gelder, Teun

    2014-10-01

    Mycophenolate mofetil (MMF) is used to prevent acute rejection following solid organ transplantation in transplant centers all over the world. Patients from different ethnic backgrounds are treated with this drug, for which therapeutic drug monitoring (TDM) has not become the standard of practice in most centers. Whether or not some ethnic groups require a different MMF dose has been a topic of debate in recent years. In this review, it is shown that Asian patients, compared with Caucasian patients, with a comparable MMF dose reach higher mycophenolic acid (MPA) exposure. Also clinical experience points toward more adverse events in case of treatment with 1 g MMF bid in Asian patients, and therefore, for this ethnic group, a lower maintenance dose seems justified. In contrast, African American patients reach similar drug concentrations as Caucasians patients receiving the same MMF dose, but due to immunological reasons, they require a higher MMF dose to reach comparable acute rejection incidences. When TDM is performed, clinicians can correct the dose and compensate for interethnic differences in drug exposure. Otherwise, it is important to choose the right dose. This optimal dose is 20-46% lower in Asian transplant recipients than in Caucasian or African American patients. © 2014 Steunstichting ESOT.

  14. Maximum a posteriori Bayesian estimation of mycophenolic Acid area under the concentration-time curve: is this clinically useful for dosage prediction yet?

    Science.gov (United States)

    Staatz, Christine E; Tett, Susan E

    2011-12-01

    This review seeks to summarize the available data about Bayesian estimation of area under the plasma concentration-time curve (AUC) and dosage prediction for mycophenolic acid (MPA) and evaluate whether sufficient evidence is available for routine use of Bayesian dosage prediction in clinical practice. A literature search identified 14 studies that assessed the predictive performance of maximum a posteriori Bayesian estimation of MPA AUC and one report that retrospectively evaluated how closely dosage recommendations based on Bayesian forecasting achieved targeted MPA exposure. Studies to date have mostly been undertaken in renal transplant recipients, with limited investigation in patients treated with MPA for autoimmune disease or haematopoietic stem cell transplantation. All of these studies have involved use of the mycophenolate mofetil (MMF) formulation of MPA, rather than the enteric-coated mycophenolate sodium (EC-MPS) formulation. Bias associated with estimation of MPA AUC using Bayesian forecasting was generally less than 10%. However some difficulties with imprecision was evident, with values ranging from 4% to 34% (based on estimation involving two or more concentration measurements). Evaluation of whether MPA dosing decisions based on Bayesian forecasting (by the free website service https://pharmaco.chu-limoges.fr) achieved target drug exposure has only been undertaken once. When MMF dosage recommendations were applied by clinicians, a higher proportion (72-80%) of subsequent estimated MPA AUC values were within the 30-60 mg · h/L target range, compared with when dosage recommendations were not followed (only 39-57% within target range). Such findings provide evidence that Bayesian dosage prediction is clinically useful for achieving target MPA AUC. This study, however, was retrospective and focussed only on adult renal transplant recipients. Furthermore, in this study, Bayesian-generated AUC estimations and dosage predictions were not compared

  15. A novel freeze-dried storage and preparation method for the determination of mycophenolic acid in plasma by high-performance liquid chromatography.

    Science.gov (United States)

    Wang, Lei; Qiang, Wei; Li, Ying; Cheng, Zeneng; Xie, Mengmeng

    2017-09-01

    Plasma samples were conventionally stored at freezing conditions until the time of detection. Such a technique, when carried out over an extended period, is energy consuming; in addition, preparation and transportation of stored samples is inconvenient. In this study, a freeze-dried storage and preparation method was proposed to determine the presence of mycophenolic acid (MPA) in plasma. Fresh plasma samples were freeze-dried using a device, and then stored at ambient temperature. After the stored samples were soaked with methanol spiked with the internal standard, high-performance liquid chromatography was conducted to detect MPA. The proposed method was demonstrated to be precise and accurate over the linear range of 0.5-50 μg mL -1 , with both intra- and inter-day precision being plasma concentration, time point of maximum plasma concentration and elimination half-life, among others, were consistent with the results in the published study. This proposed technique was proved to be simple, reproducible and energy saving. This approach could also simplify the storage and analysis of samples in clinical and scientific drug research. Copyright © 2017 John Wiley & Sons, Ltd.

  16. A six-hour extrapolated sampling strategy for monitoring mycophenolic acid in renal transplant patients in the Indian subcontinent

    Directory of Open Access Journals (Sweden)

    Fleming D

    2006-01-01

    Full Text Available Background : Therapeutic drug monitoring for mycophenolic acid (MPA is increasingly being advocated. Thepresent therapeutic range relates to the 12-hour area under the serum concentration time profile (AUC.However, this is a cumbersome, tedious, cost restricting procedure. Is it possible to reduce this samplingperiod? Aim : To compare the AUC from a reduced sampling strategy with the full 12-hour profile for MPA. Settings and Design : Clinical Pharmacology Unit of a tertiary care hospital in South India. Retrospective, paireddata. Materials and Methods : Thirty-four 12-hour profiles from post-renal transplant patients on Cellcept ® wereevaluated. Profiles were grouped according to steroid and immunosuppressant co-medication and the timeafter transplant. MPA was estimated by high performance liquid chromatography with UV detection. From the12-hour profiles the AUC up to only six hours was calculated by the trapezoidal rule and a correction factorapplied. These two AUCs were then compared. Statistical Analysis : Linear regression, intra-class correlations (ICC and a two-tailed paired t-test were appliedto the data. Results : Comparing the 12-hour AUC with the paired 6-hour extrapolated AUC, the ICC and linear regression(r2 were very good for all three groups. No statistical difference was found by a two-tailed paired t-test. Nobias was seen with a Bland Altman plot or by calculation. Conclusion : For patients on Cellcept ® with prednisolone ± cyclosporine the 6-hour corrected is an accuratemeasure of the full 12-hour AUC.

  17. Differential Sensitivities of Fast- and Slow-Cycling Cancer Cells to Inosine Monophosphate Dehydrogenase 2 Inhibition by Mycophenolic Acid

    Science.gov (United States)

    Chen, Kan; Cao, Wanlu; Li, Juan; Sprengers, Dave; Hernanda, Pratika Y; Kong, Xiangdong; van der Laan, Luc JW; Man, Kwan; Kwekkeboom, Jaap; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2015-01-01

    As uncontrolled cell proliferation requires nucleotide biosynthesis, inhibiting enzymes that mediate nucleotide biosynthesis constitutes a rational approach to the management of oncological diseases. In practice, however, results of this strategy are mixed and thus elucidation of the mechanisms by which cancer cells evade the effect of nucleotide biosynthesis restriction is urgently needed. Here we explored the notion that intrinsic differences in cancer cell cycle velocity are important in the resistance toward inhibition of inosine monophosphate dehydrogenase (IMPDH) by mycophenolic acid (MPA). In short-term experiments, MPA treatment of fast-growing cancer cells effectively elicited G0/G1 arrest and provoked apoptosis, thus inhibiting cell proliferation and colony formation. Forced expression of a mutated IMPDH2, lacking a binding site for MPA but retaining enzymatic activity, resulted in complete resistance of cancer cells to MPA. In nude mice subcutaneously engrafted with HeLa cells, MPA moderately delayed tumor formation by inhibiting cell proliferation and inducing apoptosis. Importantly, we developed a lentiviral vector–based Tet-on label-retaining system that enables to identify, isolate and functionally characterize slow-cycling or so-called label-retaining cells (LRCs) in vitro and in vivo. We surprisingly found the presence of LRCs in fast-growing tumors. LRCs were superior in colony formation, tumor initiation and resistance to MPA as compared with fast-cycling cells. Thus, the slow-cycling compartment of cancer seems predominantly responsible for resistance to MPA. PMID:26467706

  18. Mycophenolate mofetil in renal transplantation : 3-year results from the placebo-controlled trial

    NARCIS (Netherlands)

    Behrend, M; Grinyo, J; Vanrenterghem, Y; Rodicio, J; Albrechtsen, D; Sadek, S; Soulillou, JP; van Son, W; Groth, C; Mjornstedt, L; Wiesel, M; Neumayer, HH; Tufveson, G; Ekberg, H; Tarantino, A; Thiel, G; Hene, R; Morgan, A; Ramos, E; Rees, M

    1999-01-01

    Background. The European double-blind, placebo (PLA) controlled study of mycophenolate mofetil (MMF) for prevention of acute renal allograft rejection showed that MMF 2 and 3 g when added to a standard double-drug regimen of cyclosporine and corticosteroids significantly reduced the incidence of

  19. A new class of IMP dehydrogenase with a role in self-resistance of mycophenolic acid producing fungi

    Directory of Open Access Journals (Sweden)

    Mortensen Uffe H

    2011-09-01

    Full Text Available Abstract Background Many secondary metabolites produced by filamentous fungi have potent biological activities, to which the producer organism must be resistant. An example of pharmaceutical interest is mycophenolic acid (MPA, an immunosuppressant molecule produced by several Penicillium species. The target of MPA is inosine-5'-monophosphate dehydrogenase (IMPDH, which catalyses the rate limiting step in the synthesis of guanine nucleotides. The recent discovery of the MPA biosynthetic gene cluster from Penicillium brevicompactum revealed an extra copy of the IMPDH-encoding gene (mpaF embedded within the cluster. This finding suggests that the key component of MPA self resistance is likely based on the IMPDH encoded by mpaF. Results In accordance with our hypothesis, heterologous expression of mpaF dramatically increased MPA resistance in a model fungus, Aspergillus nidulans, which does not produce MPA. The growth of an A. nidulans strain expressing mpaF was only marginally affected by MPA at concentrations as high as 200 μg/ml. To further substantiate the role of mpaF in MPA resistance, we searched for mpaF orthologs in six MPA producer/non-producer strains from Penicillium subgenus Penicillium. All six strains were found to hold two copies of IMPDH. A cladistic analysis based on the corresponding cDNA sequences revealed a novel group constituting mpaF homologs. Interestingly, a conserved tyrosine residue in the original class of IMPDHs is replaced by a phenylalanine residue in the new IMPDH class. Conclusions We identified a novel variant of the IMPDH-encoding gene in six different strains from Penicillium subgenus Penicillium. The novel IMPDH variant from MPA producer P. brevicompactum was shown to confer a high degree of MPA resistance when expressed in a non-producer fungus. Our study provides a basis for understanding the molecular mechanism of MPA resistance and has relevance for biotechnological and pharmaceutical applications.

  20. Is There Evidence to Support Brand to Generic Interchange of the Mycophenolic Acid Products?

    Science.gov (United States)

    Phillips, Karen; Reddy, Prabashni; Gabardi, Steven

    2017-02-01

    The uptake of generic immunosuppressants lags comparatively to other drug classes, despite that the Food and Drug Administration (FDA) uses identical bioequivalence standards for all drugs. Transplant societies acknowledge the cost savings associated with generic immunosuppressants and support their use following heart, lung, kidney, or bone marrow transplantation. Seven studies of the pharmacokinetics or clinical efficacy of generic mycophenolate mofetil compared to the innovator product are published; all studies and products were ex-United States. Three studies did not demonstrate any pharmacokinetic differences between generic and innovator products in healthy subjects, achieving FDA bioequivalence requirements. Two studies in renal allograft recipients demonstrated no difference in area under the curves between generic and innovator products, and in one, the maximum concentration (Cmax) fell outside the FDA regulatory range. Two studies revealed no difference in acute organ rejection or graft function in renal allograft recipients. Patient surveys indicate that cost is a barrier to immunosuppressant adherence. Generics present a viable method to reduce costs to payers, patients, and health care systems. Adherence to immunosuppressants is crucial to prevent graft failure. An affordable regimen potentially confers greater adherence. Concerns regarding the presumed inferiority of generic immunosuppressants should be assuaged by regulatory requirements for bioequivalency testing, transplant society position statements, and pharmacokinetic and clinical studies.

  1. Differential proteome analysis of human embryonic kidney cell line (HEK-293 following mycophenolic acid treatment

    Directory of Open Access Journals (Sweden)

    Rahman Hazir

    2011-09-01

    Full Text Available Abstract Background Mycophenolic acid (MPA is widely used as a post transplantation medicine to prevent acute organ rejection. In the present study we used proteomics approach to identify proteome alterations in human embryonic kidney cells (HEK-293 after treatment with therapeutic dose of MPA. Following 72 hours MPA treatment, total protein lysates were prepared, resolved by two dimensional gel electrophoresis and differentially expressed proteins were identified by QTOF-MS/MS analysis. Expressional regulations of selected proteins were further validated by real time PCR and Western blotting. Results The proliferation assay demonstrated that therapeutic MPA concentration causes a dose dependent inhibition of HEK-293 cell proliferation. A significant apoptosis was observed after MPA treatment, as revealed by caspase 3 activity. Proteome analysis showed a total of 12 protein spots exhibiting differential expression after incubation with MPA, of which 7 proteins (complement component 1 Q subcomponent-binding protein, electron transfer flavoprotein subunit beta, cytochrome b-c1 complex subunit, peroxiredoxin 1, thioredoxin domain-containing protein 12, myosin regulatory light chain 2, and profilin 1 showed significant increase in their expression. The expression of 5 proteins (protein SET, stathmin, 40S ribosomal protein S12, histone H2B type 1 A, and histone H2B type 1-C/E/F/G/I were down-regulated. MPA mainly altered the proteins associated with the cytoskeleton (26%, chromatin structure/dynamics (17% and energy production/conversion (17%. Both real time PCR and Western blotting confirmed the regulation of myosin regulatory light chain 2 and peroxiredoxin 1 by MPA treatment. Furthermore, HT-29 cells treated with MPA and total kidney cell lysate from MMF treated rats showed similar increased expression of myosin regulatory light chain 2. Conclusion The emerging use of MPA in diverse pathophysiological conditions demands in-depth studies to

  2. Safety of reduced dose of mycophenolate mofetil combined with tacrolimus in living-donor liver transplantation

    Directory of Open Access Journals (Sweden)

    Hyeyoung Kim

    2014-09-01

    Full Text Available Background/AimsThe dose of mycophenolate mofetil (MMF has been reduced in Asia due to side effects associated with the conventional fixed dose of 2-3 g/day. We aimed to determine the pharmacokinetics of a reduced dose of MMF and to validate its feasibility in combination with tacrolimus in living-donor liver transplantation (LDLT.MethodsTwo sequential studies were performed in adult LDLT between October 2009 and 2011. First, we performed a prospective pharmacokinetic study in 15 recipients. We measured the area under the curve from 0 to 12 hours (AUC0-12 for mycophenolic acid at postoperative days 7 and 14, and we performed a protocol biopsy before discharge. Second, among 215 recipients, we reviewed 74 patients who were initially administered a reduced dose of MMF (1.0 g/day with tacrolimus (trough, 8-12 ng/mL during the first month, and 5-8 ng/mL thereafter, with a 1-year follow-up. We performed protocol biopsies at 2 weeks and 1 year post-LDLT.ResultsIn the first part of study, AUC0-12 was less than 30 mgh/L in 93.3% of cases. In the second, validating study, 41.9% of the recipients needed dose reduction or cessation due to side effects within the first year after LDLT. At 12 months post-LDLT, 17.6% of the recipients were administered a lower dose of MMF (0.5 g/day, and 16.2% needed permanent cessation due to side effects. The 1- and 12-month rejection-free survival rates were 98.6% and 97.3%, respectively.ConclusionsA reduced dose of MMF was associated with low blood levels compared to the existing recommended therapeutic range. However, reducing the dose of MMF combined with a low level of tacrolimus was feasible clinically, with an excellent short-term outcome in LDLT.

  3. Enteric-coated mycophenolate sodium experience in liver transplant patients.

    Science.gov (United States)

    Cantisani, G P C; Zanotelli, M L; Gleisner, A L M; de Mello Brandão, A; Marroni, C A

    2006-04-01

    Mycophenolate sodium (EC-MPS) has been shown to be as effective and as safe as mycophenolate mofetil (MMF) in renal transplant patients. Nevertheless, compared to MMF its use in liver transplant patients has been limited. The purpose of this study was to analyze the efficacy of EC-MPS as a primary immunosuppressant or as a replacement for MMF in liver transplant patients. Ninety among 470 liver transplant recipients were receiving or had added an antimetabolite to their immunosuppressant therapy. The most common reason for this change was renal dysfunction (47.8%) or diabetes (32.2%). EC-MPS was started at a median of 30 months after liver transplantation. The mean administered daily dose was 720 mg/d. At least one gastrointestinal symptom was reported by 25 patients. Abdominal pain (16.6%) and diarrhea (14.5%) were the most frequent. EC-MPS had to be discontinued in two patients, while six others required dose reduction to resolve the symptoms. Hematological adverse events were infrequent: three patients had leukopenia and one, anemia, all of which responded to dosage reduction. There was a creatinine reduction within 6 months of drug commencement and maintenance of the lower creatinine levels at 1 year among patients who began EC-MPS for renal dysfunction. Serum low-density lipoprotein cholesterol and triglyceride levels were significantly lower among patients on EC-MPS than on MMF. In conclusion, EC-MPS appears to have a similar efficacy and safety profile as MMF in liver transplant patients. Hematological and gastrointestinal adverse events were infrequent; seldom had the drug to be discontinued.

  4. Evaluation of Multiple Linear Regression-Based Limited Sampling Strategies for Enteric-Coated Mycophenolate Sodium in Adult Kidney Transplant Recipients.

    Science.gov (United States)

    Brooks, Emily K; Tett, Susan E; Isbel, Nicole M; McWhinney, Brett; Staatz, Christine E

    2018-04-01

    Although multiple linear regression-based limited sampling strategies (LSSs) have been published for enteric-coated mycophenolate sodium, none have been evaluated for the prediction of subsequent mycophenolic acid (MPA) exposure. This study aimed to examine the predictive performance of the published LSS for the estimation of future MPA area under the concentration-time curve from 0 to 12 hours (AUC0-12) in renal transplant recipients. Total MPA plasma concentrations were measured in 20 adult renal transplant patients on 2 occasions a week apart. All subjects received concomitant tacrolimus and were approximately 1 month after transplant. Samples were taken at 0, 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, and 8 hours and 0, 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 4, 6, 9, and 12 hours after dose on the first and second sampling occasion, respectively. Predicted MPA AUC0-12 was calculated using 19 published LSSs and data from the first or second sampling occasion for each patient and compared with the second occasion full MPA AUC0-12 calculated using the linear trapezoidal rule. Bias (median percentage prediction error) and imprecision (median absolute prediction error) were determined. Median percentage prediction error and median absolute prediction error for the prediction of full MPA AUC0-12 were multiple linear regression-based LSS was not possible without concentrations up to at least 8 hours after the dose.

  5. Use of mycophenolate mofetil in patients with severe localized scleroderma resistant or intolerant to methotrexate

    NARCIS (Netherlands)

    Mertens, Jorre S.; Marsman, Diane; van de Kerkhof, Peter C M; Hoppenreijs, Esther P A H; Knaapen, Hanneke K A; Radstake, Timothy R D; de Jong, Elke M G J; Seyger, Marieke M B

    2016-01-01

    To assess the efficacy and safety of mycophenolate mofetil (MMF) in patients with localized scleroderma (LoS) resistant or intolerant to previous treatment with methotrexate (MTX). A case series of patients with LoS treated with MMF. Outcome was assessed through clinical examination. Adverse events

  6. A comprehensive review of the published assays for the quantitation of the immunosuppressant drug mycophenolic acid and its glucuronidated metabolites in biological fluids.

    Science.gov (United States)

    Syed, Muzeeb; Srinivas, Nuggehally R

    2016-05-01

    Therapeutic use of mycophenolic acid (MPA) is steadily on the rise in combination with other immunosuppressant drugs in transplantation patients. The biotransformation of MPA resulted in the formation of glucuronide metabolites, MPAG and AcMPAG. There are a plethora of assays validated for the analysis of MPA alone or with MPAG/AcMPAG in various biological specimens including plasma/serum, urine, ultrafiltrate, saliva, PBMC, dried blood spots, tissue extract, tumor biopsies and vitreous humor. Based on the need for experimental work, a proper choice of the assay and internal standard may be made using the choices in the literature. While the chemical methods involving high-performance liquid chromatography (HPLC) or LC coupled with triple quadrupole mass spectrometry (LC-MS/MS) are popular, enzymatic assays, in spite of their higher bias, have been used for the routine drug monitoring of MPA. The objectives of the present review are: (a) to provide a focused systematic compilation of the HPLC or LC-MS/MS methods for MPA, MPAG and/or AcMPAG published in the last decade (2005 to current) to enable visual comparison of the methods; (b) to compare and contrast a few enzymatic assays with those of the chemical methods; and (c) to discuss relevant issues/limitations and perspectives on select assays under various subheadings. Copyright © 2016 John Wiley & Sons, Ltd.

  7. PLACEBO-CONTROLLED STUDY OF MYCOPHENOLATE MOFETIL COMBINED WITH CYCLOSPORINE AND CORTICOSTEROIDS FOR PREVENTION OF ACUTE REJECTION

    NARCIS (Netherlands)

    GRINYO, J; GROTH, C; PICHLMAYR, R; SADEK, SA; VANRENTERGHEM, Y; BEHREND, M; LUCK, R; MORESO, F; PEETERS, J; RODICIO, J; MORALES, J; ALBRECHTSEN, D; FAUCHALD, P; SADEK, S; LODGE, J; SOULILLOU, JP; CANTAROVICH, D; van Son, W; Tegzess, Adam; WAGNER, K; ERHARD, J; BRATTSTROM, C; MJORNSTEDT, L; WIESEL, M; CARL, S; NEUMAYER, HH; HAUSER, [No Value; LANG, P; BOURGEON, B; TUFVESON, G; GANNEDAHL, G; EKBERG, H; PERSSON, N; TARANTINO, A; CAMPISE, M; THIEL, G; ZEILER, M; HENE, R; LIGTENBERG, G; MORGAN, A; RIGG, K; HOOFTMAN, L; HUTCHINSON, K

    1995-01-01

    Preliminary studies suggested that mycophenolate mofetil (MMF), which inhibits proliferation of T and B cells, may reduce the frequency of acute rejection after renal transplantation. Our randomised, double-blind, multicentre, placebo-controlled study compared the efficacy and safety of MMF with

  8. Calcineurin inhibitor sparing with mycophenolate in kidney transplantation: a systematic review and meta-analysis.

    LENUS (Irish Health Repository)

    Moore, Jason

    2009-02-27

    Limiting the exposure of kidney transplant recipients to calcineurin inhibitors (CNIs) has potential merit, but there is no clear consensus on the utility of current strategies. In an attempt to aid clarification, we conducted a systematic review and meta-analysis of randomized trials that assessed CNI sparing (minimization or elimination) with mycophenolate as sole adjunctive immunosuppression.

  9. Amino acid nitrosation products as alkylating agents.

    Science.gov (United States)

    García-Santos, M del P; Calle, E; Casado, J

    2001-08-08

    Nitrosation reactions of alpha-, beta-, and gamma-amino acids whose reaction products can act as alkylating agents of DNA were investigated. To approach in vivo conditions for the two-step mechanism (nitrosation and alkylation), nitrosation reactions were carried out in aqueous acid conditions (mimicking the conditions of the stomach lumen) while the alkylating potential of the nitrosation products was investigated at neutral pH, as in the stomach lining cells into which such products can diffuse. These conclusions were drawn: (i) The alkylating species resulting from the nitrosation of amino acids with an -NH(2) group are the corresponding lactones; (ii) the sequence of alkylating power is: alpha-lactones > beta-lactones > gamma-lactones, coming respectively from the nitrosation of alpha-, beta-, and gamma-amino acids; and (iii) the results obtained may be useful in predicting the mutagenic effectiveness of the nitrosation products of amino acids.

  10. Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.

    Science.gov (United States)

    Lee, DaHae; Keymeulen, Bart; Hilbrands, Robert; Ling, Zhidong; Van de Velde, Ursule; Jacobs-Tulleneers-Thevissen, Daniel; Maleux, Geert; Lapauw, Bruno; Crenier, Laurent; De Block, Christophe; Mathieu, Chantal; Pipeleers, Daniel; Gillard, Pieter

    2017-09-01

    Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.

  11. Cinnamic Acid Derivatives as Antidiabetics Agents

    Directory of Open Access Journals (Sweden)

    Teni Ernawati

    2017-04-01

    Full Text Available Diabetes mellitus is a metabolic disorder of carbohydrate metabolism. Treatment of type II diabetes is usually done by prescribing diet and exercise for the patient however it can also be treated with antidiabetic drugs. The purpose of this paper is to illustrate some cinnamic acid derivative compounds which are either isolated from natural materials or the results of the chemical synthesis. In addition, their biological activities as an agent of α-glucosidase inhibitors have also been evaluated. Chemically, cinnamic acid has three main functional groups:  first is the substitution on the phenyl group, second is the additive reaction into the α-β unsaturated, and third is the chemical reaction with carboxylic acid functional groups. Chemical aspects of cinnamic acid derivative compounds have received much attention in the research and development of drugs, especially modifications within three functional groups are very influential. In the last 10 years, a lot of research and development of cinnamic acid derivatives as inhibitors of the α-glucosidase enzyme has been done. One example of the research done in this field is the modification of para position in the structure of cinnamic acid and addition of alkyl groups in the carboxylic group which would increase the activity of the α-glucosidase enzyme therefore the level of inhibition is 100 times higher than that of cinnamic acid compound itself. The novelty of this review article is to focus on the antidiabetic activity of cinnamic acid derivatives.

  12. Efficacy and Safety of Mycophenolate Mofetil and Tacrolimus as Second-line Therapy for Patients With Autoimmune Hepatitis

    DEFF Research Database (Denmark)

    Efe, Cumali; Hagström, Hannes; Ytting, Henriette

    2017-01-01

    BACKGROUND & AIMS: Predniso(lo)ne, alone or in combination with azathioprine, is the standard-of-care (SOC) therapy for autoimmune hepatitis (AIH). However, the SOC therapy is poorly tolerated or does not control disease activity in up to 20% of patients. We assessed the efficacy of mycophenolate...

  13. Study of Ascorbic Acid as Iron(III Reducing Agent for Spectrophotometric Iron Speciation

    Directory of Open Access Journals (Sweden)

    Antesar Elmagirbi

    2012-10-01

    Full Text Available The study of ascorbic acid as a reducing agent for iron(III has been investigated in order to obtain an alternative carcinogenic reducing agent, hydroxylamine, used in spectrophotometric standard method based on the formation of a red-orange complex of Fe(II-o-phenanthroline. The study was optimised with regards to ascorbic acid concentration as well as pH solution. The results showed that ascorbic acid showed maximum capacity as reducing agent of iron(III under concentration of 4.46.10-4 M and pH solution of 1-4.Under these conditions, ascorbic acid reduced iron(III proportionally and performed similarly to that of hydroxylamine.  The method gave result to linear calibration over the range of 0.2-2 mg/L withhigh accuracy of 97 % and relative standard deviation of less than 2 %. This method was successfully applied to assay iron speciation in water samples.

  14. Formamidine sulfinic acid as reducing agent in technetium-99m rhenium sulfide labelling

    Energy Technology Data Exchange (ETDEWEB)

    Neves, M; Patricio, L [Laboratorio Nacional de Engenharia e Technologia Industrial, Sacavem (Portugal). Dept. de Radioisotopes; Ferronha, H [Laboratorio Nacional de Investigacao Veterinaria, Lisboa (Portugal)

    1989-08-01

    Labelling kinetic studies, radiochemical characterization and particle size evaluation of {sup 99m}Tc rhenium sulfide colloid using formamidine sulfinic acid as reducing agent are described. Comparison with the same colloid which makes use of Sn-sodium pyrophosphate complex as reducing agent showed higher labelling yields, simplification of labelling procedure and a longer shelf life when formamidine sulfinic acid was used. (author) 15 refs.; 7 figs.

  15. Spherical Nucleic Acids as Intracellular Agents for Nucleic Acid Based Therapeutics

    Science.gov (United States)

    Hao, Liangliang

    Recent functional discoveries on the noncoding sequences of human genome and transcriptome could lead to revolutionary treatment modalities because the noncoding RNAs (ncRNAs) can be applied as therapeutic agents to manipulate disease-causing genes. To date few nucleic acid-based therapeutics have been translated into the clinic due to challenges in the delivery of the oligonucleotide agents in an effective, cell specific, and non-toxic fashion. Unmodified oligonucleotide agents are destroyed rapidly in biological fluids by enzymatic degradation and have difficulty crossing the plasma membrane without the aid of transfection reagents, which often cause inflammatory, cytotoxic, or immunogenic side effects. Spherical nucleic acids (SNAs), nanoparticles consisting of densely organized and highly oriented oligonucleotides, pose one possible solution to circumventing these problems in both the antisense and RNA interference (RNAi) pathways. The unique three dimensional architecture of SNAs protects the bioactive oligonucleotides from unspecific degradation during delivery and supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. Owing to their unique structure, SNAs are able to cross cell membranes and regulate target genes expression as a single entity, without triggering the cellular innate immune response. Herein, my thesis has focused on understanding the interactions between SNAs and cellular components and developing SNA-based nanostructures to improve therapeutic capabilities. Specifically, I developed a novel SNA-based, nanoscale agent for delivery of therapeutic oligonucleotides to manipulate microRNAs (miRNAs), the endogenous post-transcriptional gene regulators. I investigated the role of SNAs involving miRNAs in anti-cancer or anti-inflammation responses in cells and in in vivo murine disease models via systemic injection. Furthermore, I explored using different strategies to construct

  16. An experimental study for efficacy of acetic acid as a sclerosing agent

    International Nuclear Information System (INIS)

    Kim, Young Chan; Oh, Ju Hyung; Yoon, Yup; Ko, Young Tae; Choi, Woo Suk; Kim, Eui Jong; Lim, Joo Won

    1997-01-01

    To evaluate the efficacy of acetic acid as a sclerosing agent by observation of histologic change in urinary bladder epithelium after the instillation of acetic acid. Urinary bladder of the rabbit was catheterized with a Foley catheter, and acetic acid of 10%, 20%, 30%, 40% and 50% concentration was instilled for 5 minutes. After evacuation of the acid, the bladder was irrigated three times with normal saline. After two days, gross and histologic examinations of the bladder were performed. A bladder into which 10% acetic acid had been instilled revealed a nearly normal epithelium without denudation. In two cases, 20% acetic acid was instilled;one revealed partial denudation of the epithelium and the other revealed complete denudation. Mild to moderate interstitial edema and vascular congestion of the bladder wall were evident in all cases in which acid at a concentration of 30% or more had been instilled. In all cases in which the concentration of acid was greater than 30%, the epithelium was completely denuded. An acetic acid concentration of 40% or more is sufficient to completely destroy the epithelium of rabbit urinary bladder, and may be effective as a new sclerosing agent in cases of renal or hepatic cyst

  17. Effect of acidic agents on surface roughness of dental ceramics

    Directory of Open Access Journals (Sweden)

    Boonlert Kukiattrakoon

    2011-01-01

    Conclusion: Acidic agents used in this study negatively affected the surface of ceramic materials. This should be considered when restoring the eroded tooth with ceramic restorations in patients who have a high risk of erosive conditions.

  18. Soil washing of chromium- and cadmium-contaminated sludge using acids and ethylenediaminetetra acetic acid chelating agent.

    Science.gov (United States)

    Gitipour, Saeid; Ahmadi, Soheil; Madadian, Edris; Ardestani, Mojtaba

    2016-01-01

    In this research, the effect of soil washing in the removal of chromium- and cadmium-contaminated sludge samples collected from Pond 2 of the Tehran Oil Refinery was investigated. These metals are considered as hazardous substances for human health and the environment. The carcinogenicity of chromate dust has been established for a long time. Cadmium is also a potential environmental toxicant. This study was carried out by collecting sludge samples from different locations in Pond 2. Soil washing was conducted to treat the samples. Chemical agents, such as acetic acid, ethylenediaminetetra acetic acid (EDTA) and hydrochloric acid, were used as washing solutions to remove chromium and cadmium from sludge samples. The results of this study indicated that the highest removal efficiencies from the sludge samples were achieved using a 0.3 M HCl solution with 82.69% and 74.47% for chromium and cadmium, respectively. EDTA (0.1 M) in the best condition extracted 66.81% of cadmium and 72.52% of chromium from the sludges. The lowest efficiency values for the samples, however, were achieved using 3 M acetic acid with 41.7% and 46.96% removals for cadmium and chromium, respectively. The analysis of washed sludge indicated that the heavy metals removal decreased in the order of 3 M acetic acid < 0.1 M EDTA<0.3 M HCl, thus hydrochloric acid appears to offer a greater potential as a washing agent in remediating the sludge samples.

  19. Synthesis of mutual azo prodrugs of anti-inflammatory agents and peptides facilitated by α-aminoisobutyric acid.

    Science.gov (United States)

    Kennedy, David A; Vembu, Nagarajan; Fronczek, Frank R; Devocelle, Marc

    2011-12-02

    Reported is the synthesis of azo mutual prodrugs of the nonsteroidal anti-inflammatory agents (NSAIDs) 4-aminophenylacetic acid (4-APAA) or 5-aminosalicylic acid (5-ASA) with peptides, including an antibiotic peptide temporin analogue modified at the amino terminal by an α-aminoisobutyric acid (Aib) residue. These prodrugs are designed for colonic delivery of two agents to treat infection and inflammation by the bacterial pathogen Clostridium difficile . © 2011 American Chemical Society

  20. Mycophenolate sodium for the treatment of chronic non-infectious uveitis of childhood.

    Science.gov (United States)

    Doycheva, Deshka; Zierhut, Manfred; Blumenstock, Gunnar; Sobolewska, Bianka; Voykov, Bogomil; Hohmann, Johanna; Spitzer, Martin S; Deuter, Christoph

    2016-08-01

    To assess the efficacy and tolerability of mycophenolate sodium (MPS) in the therapy of children with chronic non-infectious uveitis. Retrospective analysis of 23 children with chronic uveitis, treated with MPS, with a follow-up of at least 6 months. The main outcome measures were time to uveitis reactivation and corticosteroid-sparing effect under MPS treatment. The secondary outcome measures were best-corrected visual acuity (BCVA) and treatment-related side effects. From 23 patients included in the study, 2 patients had anterior uveitis, 19 had intermediate uveitis and 2 had panuveitis. The probability of reactivation-free survival after MPS initiation was estimated as 65% at both 1 and 2 years. The probability of discontinuing systemic corticosteroids after 1 year of treatment was 39% and after 2 years 51%. The probability to taper corticosteroids to a daily dosage of ≤0.1 mg/kg after 1 and 2 years was 62% and 85%, respectively. BCVA improved or remained stable in 96% of eyes after 1 year of therapy. Treatment-related side effects were found in nine children (rate: 0.17/patient-year). No therapy discontinuation because of side effects was needed. Our data suggest that MPS is useful and well tolerated in children with chronic uveitis. MPS seems to be an effective drug for the treatment of chronic non-infectious uveitis of childhood and may be preferred as a first-line steroid-sparing agent in this form of uveitis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Poly (amido amine) and nano-calcium phosphate bonding agent to remineralize tooth dentin in cyclic artificial saliva/lactic acid

    Energy Technology Data Exchange (ETDEWEB)

    Liang, Kunneng [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Weir, Michael D.; Reynolds, Mark A. [Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Zhou, Xuedong [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Li, Jiyao, E-mail: jiyaoliscu@163.com [State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu 610041 (China); Xu, Hockin H.K., E-mail: hxu@umaryland.edu [Department of Endodontics, Periodontics and Prosthodontics, University of Maryland School of Dentistry, Baltimore, MD 21201 (United States); Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201 (United States); Department of Mechanical Engineering, University of Maryland Baltimore County, Baltimore County, MD 21250 (United States)

    2017-03-01

    The objectives of this study were to develop a novel method to remineralize dentin lesions, and investigate the remineralization effects of poly (amido amine) (PAMAM) dendrimer plus a bonding agent with nanoparticles of amorphous calcium phosphate (NACP) in a cyclic artificial saliva/lactic acid environment for the first time. Dentin lesions were produced via phosphoric acid. Four groups were tested: (1) dentin control, (2) dentin with PAMAM, (3) dentin with NACP bonding agent, and (4) dentin with PAMAM plus NACP bonding agent. Specimens were treated with cyclic artificial saliva/lactic acid. The remineralized dentin was examined using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), hardness and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). NACP bonding agent yielded a dentin shear bond strength similar to commercial controls (Prime & Bond NT, Dentsply; Scotchbond Multi-purpose, 3M) (p > 0.1). Increasing NACP in bonding agent from 0 to 40% did not affect bond strength. NACP bonding agent neutralized the acid and released Ca ions with concentrations of 4 to 20 mmol/L, and P ions of 2 to 9 mmol/L. PAMAM or NACP bonding agent alone achieved slight remineralization. The PAMAM + NACP group achieved the greatest dentin remineralization p < 0.05). At 20 days, PAMAM + NACP increased the hardness of pre-demineralized dentin to reach the normal dentin hardness (p > 0.1). In conclusion, superior remineralization of PAMAM + NACP bonding agent was demonstrated for the first time. PAMAM + NACP bonding agent induced dentin remineralization under acid challenge, when conventional remineralization methods such as PAMAM alone did not work well. The novel PAMAM + NACP bonding agent method is promising to improve the longevity of resin-dentin bonds, inhibit caries, and protect teeth. - Highlights: • PAMAM induced moderate remineralization for dentin in artificial saliva/lactic acid. • Acid challenge reduced the

  2. Poly (amido amine) and nano-calcium phosphate bonding agent to remineralize tooth dentin in cyclic artificial saliva/lactic acid

    International Nuclear Information System (INIS)

    Liang, Kunneng; Weir, Michael D.; Reynolds, Mark A.; Zhou, Xuedong; Li, Jiyao; Xu, Hockin H.K.

    2017-01-01

    The objectives of this study were to develop a novel method to remineralize dentin lesions, and investigate the remineralization effects of poly (amido amine) (PAMAM) dendrimer plus a bonding agent with nanoparticles of amorphous calcium phosphate (NACP) in a cyclic artificial saliva/lactic acid environment for the first time. Dentin lesions were produced via phosphoric acid. Four groups were tested: (1) dentin control, (2) dentin with PAMAM, (3) dentin with NACP bonding agent, and (4) dentin with PAMAM plus NACP bonding agent. Specimens were treated with cyclic artificial saliva/lactic acid. The remineralized dentin was examined using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), hardness and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). NACP bonding agent yielded a dentin shear bond strength similar to commercial controls (Prime & Bond NT, Dentsply; Scotchbond Multi-purpose, 3M) (p > 0.1). Increasing NACP in bonding agent from 0 to 40% did not affect bond strength. NACP bonding agent neutralized the acid and released Ca ions with concentrations of 4 to 20 mmol/L, and P ions of 2 to 9 mmol/L. PAMAM or NACP bonding agent alone achieved slight remineralization. The PAMAM + NACP group achieved the greatest dentin remineralization p < 0.05). At 20 days, PAMAM + NACP increased the hardness of pre-demineralized dentin to reach the normal dentin hardness (p > 0.1). In conclusion, superior remineralization of PAMAM + NACP bonding agent was demonstrated for the first time. PAMAM + NACP bonding agent induced dentin remineralization under acid challenge, when conventional remineralization methods such as PAMAM alone did not work well. The novel PAMAM + NACP bonding agent method is promising to improve the longevity of resin-dentin bonds, inhibit caries, and protect teeth. - Highlights: • PAMAM induced moderate remineralization for dentin in artificial saliva/lactic acid. • Acid challenge reduced the

  3. Peracetic acid as a superior oxidant for preparation of [123I]IBZM: a potential dopamine D-2 receptor imaging agent

    International Nuclear Information System (INIS)

    Kung, Meiping; Kung, H.F.

    1989-01-01

    Various oxidizing agents: chloramine-T, hydrogen peroxide, sodium persulfate, m-chloroperoxybenzoic acid and peracetic acid were examined as the oxidant for preparing radioiodinated IBZM ((S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzami de), which is a useful dopamine D-2 receptor imaging agent. Of all the oxidizing agents tested, peracetic acid appears to be the best agent for no-carrier added radioiodination. The advantages of using peracetic acid as the oxidant for the preparation of [ 125 I] or [ 123 I] IBZM include: high radiochemical yield, high radiochemical purity, and short reaction time at room temperature. (Author)

  4. Effectiveness of cyclosporine and mycophenolate mofetil in a child with refractory evans syndrome

    Directory of Open Access Journals (Sweden)

    Piero Farruggia

    2011-05-01

    Full Text Available Evans Syndrome is a rare autoimmune disease consisting of hemolytic anemia, thrombocytopenia and/or neutropenia. It may be associated with other autoimmune or lymphoproliferative diseases. Its course can be extremely serious and, rarely, even life-threatening; thus it represents a excellent treatment challenge for the pediatric hematologist. First line treatment consists of steroids and/or immunoglobulin; further therapy with rituximab, vincristine, cyclophosphamide and other immunosuppressive drugs can be considered in unresponsive patients. We describe a baby with refractory Evans Syndrome that was cured by prolonged administration of mycophenolate mofetil and remained disease-free for 4 years after the discontinuation of treatment.

  5. Mycophenolate mofetil embryopathy: A newly recognized teratogenic syndrome.

    Science.gov (United States)

    Perez-Aytes, Antonio; Marin-Reina, Purificacion; Boso, Virginia; Ledo, Ana; Carey, John C; Vento, Maximo

    2017-01-01

    Mycophenolate mofetil (MMF) is probably the most common employed immunosuppressant drug in recipients of solid organ transplant and in many autoimmune diseases. In vitro studies, a significant number of single clinical observations and a recent study from a group of different European teratogen information services, have provided very consistent data supporting the existence of a specific MMF embryopathy. The typical malformative pattern of MMF embryopathy includes external ear anomalies ranging from hypoplastic pinna (microtia) to complete absence of pinna (anotia); cleft lip, with or without cleft palate, and ocular anomalies as iris or chorioretinal coloboma and anophthalmia/microphthalmia. Other less frequent features are congenital heart defects, distal limbs anomalies, esophageal atresia, vertebral malformations, diaphragmatic hernia, and kidney and central nervous system anomalies. Neurodevelopmental outcome seems favorable in the small number of patients where information about this issue is available, but neurological deficits have been documented. Physicians in charge of women under MMF therapy should be aware of the potential risk of this drug to cause a specific embryopathy and the need of interrupting the treatment at least six weeks before becoming pregnant. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Mechanisms of oxide dissolution by acid chelating agents

    International Nuclear Information System (INIS)

    Blesa, M.A.; Maroto, A.J.G.

    1982-01-01

    In this paper, the different possible rate controlling processes in the dissolution of metallic oxides are examined. In particular, the following situations are assessed: mass-transfer control; coupling of mass-transfer and reactions at the interface; interface equilibration with the solution; various interface disruption and reconstruction phenomena. For each of the above mentioned cases, the influence of variables such as reagent concentration, temperature, pH, fluid hydrodynamics and general and specific catalysts is discussed. Depending upon the particular situation it is found that a more rational basis for the development of reagent is given by these considerations. The influence of chelating agents on both the thermodynamics and kinetics of the process is discussed, and the results of experimental studies in batch on magnetite and various ferrites are presented and discussed. For this purpose, several reagents were studied, including some very effective ones like thioglycolic acid, and others commonly used in actual decontamination, like ethylenediaminetetraacetic acid and oxalic acid. The relation to other (reductive) chemical decontamination procedures is discussed. The relevance of these studies to decontamination of metallic surfaces is discussed

  7. Immunotherapeutics in Pediatric Autoimmune Central Nervous System Disease: Agents and Mechanisms.

    Science.gov (United States)

    Nosadini, Margherita; Sartori, Stefano; Sharma, Suvasini; Dale, Russell C

    2017-08-01

    Beyond the major advances produced by careful clinical-radiological phenotyping and biomarker development in autoimmune central nervous system disorders, a comprehensive knowledge of the range of available immune therapies and a deeper understanding of their action should benefit therapeutic decision-making. This review discusses the agents used in neuroimmunology and their mechanisms of action. First-line treatments typically include corticosteroids, intravenous immunoglobulin, and plasmapheresis, while for severe disease second-line "induction" agents such as rituximab or cyclophosphamide are used. Steroid-sparing agents such as mycophenolate, azathioprine, or methotrexate are often used in potentially relapsing or corticosteroid-dependent diseases. Lessons from adult neuroimmunology and rheumatology could be translated into pediatric autoimmune central nervous system disease in the future, including the potential utility of monoclonal antibodies targeting lymphocytes, adhesion molecules for lymphocytic migration, cytokines or their receptors, or complement. Finally, many agents used in other fields have multiple mechanisms of action, including immunomodulation, with potential usefulness in neuroimmunology, such as antibiotics, psychotropic drugs, probiotics, gut health, and ketogenic diet. All currently accepted and future potential agents have adverse effects, which can be severe; therefore, a "risk-versus-benefit" determination should guide therapeutic decision-making. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Treatment of wastes arising from decontamination process using citric acid as a decontaminate agent

    International Nuclear Information System (INIS)

    Mierzwa, J.C.; Riella, H.G.; Carvalho, E.U. de

    1993-01-01

    Wastes arising from equipment decontamination processes from nuclear fuel cycle facilities at Coordenacao de Projetos Especiais - Comissao Nacional de Energia Nuclear, Sao Paulo (COPESP-CNEN/SP) has been studied after using citric acid as a decontaminate agent. Precipitation of uranium and metallic impurities resulted from use of sodium hydroxide or calcium oxide plus a flocculation agent. The removal efficient of uranium was 95% and 99% for sodium hydroxide and calcium oxide respectively. The results shows that this process can be used to test wastes from decontamination processes which use citric acid. (B.C.A.). 03 refs, 08 figs, 04 tabs

  9. Rational Discovery of (+) (S) Abscisic Acid as a Potential Antifungal Agent: a Repurposing Approach.

    Science.gov (United States)

    Khedr, Mohammed A; Massarotti, Alberto; Mohamed, Maged E

    2018-06-04

    Fungal infections are spreading widely worldwide, and the types of treatment are limited due to the lack of diverse therapeutic agents and their associated side effects and toxicity. The discovery of new antifungal classes is vital and critical. We discovered the antifungal activity of abscisic acid through a rational drug design methodology that included the building of homology models for fungal chorismate mutases and a pharmacophore model derived from a transition state inhibitor. Ligand-based virtual screening resulted in some hits that were filtered using molecular docking and molecular dynamic simulations studies. Both in silico methods and in vitro antifungal assays were used as tools to select and validate the abscisic acid repurposing. Abscisic acid inhibition assays confirmed the inhibitory effect of abscisic acid on chorismate mutase through the inhibition of phenylpyruvate production. The repositioning of abscisic acid, the well-known and naturally occurring plant growth regulator, as a potential antifungal agent because of its suggested action as an inhibitor to several fungal chorismate mutases was the main result of this work.

  10. Solution of Azelaic Acid (20%), Resorcinol (10%) and Phytic Acid (6%) Versus Glycolic Acid (50%) Peeling Agent in the Treatment of Female Patients with Facial Melasma.

    Science.gov (United States)

    Faghihi, Gita; Taheri, Azam; Shahmoradi, Zabihollah; Nilforoushzadeh, Mohammad Ali

    2017-01-01

    Melasma, a common acquired disorder of hyperpigmentation, especially in women, is often resistant to therapy. This study was aimed to evaluate the efficacy and safety of azelaic acid, resorcinol and phytic acid solution in chemical peeling of melasma in comparison to 50% glycolic acid. This clinical trial was performed, on 42 female patients with bilateral melasma. Severity of melasma was assessed by melasma area and severity index (MASI). Combination of (20% azelaic acid + 10% resorcinol + 6% phytic acid) was used as a new peeling agent on the right side of the face and 50% glycolic acid on the left side every 2 weeks for 6 times. Follow-up was carried out for 3 months after the last session. Any decrease in MASI score and unwanted complications following peeling were evaluated and compared during the trial. Patients showed marked improvement as calculated with MASI score before and after treatment in both sides of the face. The efficacy of combination formula (azelaic acid, resorcinol and phytic acid) was similar to glycolic acid, but with fewer complications. There was no statistically difference in improvement between two groups ( P > 0.05). However, the patient's discomfort following procedures was significantly lower with azelaic acid, resorcinol and phytic compared with the glycolic acid peels ( P < 0.05) and there was the same duration in the beginning of the therapeutic response in both groups. Results showed that triple-combination was found to be an effective and safe peeling agent in the treatment of melasma and it was as effective as 50% glycolic acid peel.

  11. Catalytic properties of graphene–metal nanoparticle hybrid prepared using an aromatic amino acid as the reducing agent

    International Nuclear Information System (INIS)

    Adhikari, Bimalendu; Banerjee, Arindam

    2013-01-01

    An easy and single step process of making reduced graphene oxide nanosheet from graphene oxide (GO) in water medium has been demonstrated by using a naturally occurring non-proteinaceous amino acid (2,4-dihydroxy phenyl alanine, Dopa) as a new reducing agent and stabilizing agent. This amino acid has also been used to reduce the noble metal salt (AuCl 3 /AgNO 3 ) to produce the corresponding noble metal nanoparticles (MNP) without using any external reducing and stabilizing agents. So, this amino acid has been used to reduce simultaneously GO to RGO and noble metal salts to produce corresponding MNP to form RGO–MNP nanohybrid system in a single step in water medium and also in absence of any external toxic reducing and stabilizing agents. Different techniques UV–Visible absorption spectroscopy, X-ray diffraction, transmission electron microscopy, atomic force microscopy and others have been used to characterize the reduction of GO to RGO, metal salts to produce corresponding MNPs and the formation of RGO–MNP nanohybrid systems. Moreover, this metal nanoparticle containing RGO–MNP nanohybrid system acts as a potential catalyst for the reduction of aromatic nitro to aromatic amino group. - Graphical abstract: This study demonstrates an easy, single step and eco-friendly method to make RGO and Au/AgNP simultaneously from respective precursors to form a RGO–Au/AgNP nanohybrid system using an aromatic amino acid (2,4-dihydroxy phenyl alanine, Dopa) as a new reducing agent as well as stabilizing agent in water medium. Highlights: ► Synthesis of reduced graphene oxide (RGO) nanosheet using an amino acid. ► The amino acid (Dopa) can reduce noble metal salt (Au 3+ /Ag + ) to metal nanoparticle (MNP). ► Single step and eco-friendly synthesis of RGO-MNP nanohybrid using Dopa. ► Characterization of RGO, MNP and RGO–MNP nanohybrid. ► RGO-MNP nanohybrid acts as a catalyst for the reduction of aromatic nitro

  12. Inosine monophosphate dehydrogenase messenger RNA expression is correlated to clinical outcomes in mycophenolate mofetil-treated kidney transplant patients, whereas inosine monophosphate dehydrogenase activity is not

    NARCIS (Netherlands)

    Sombogaard, Ferdi; Peeters, Annemiek M. A.; Baan, Carla C.; Mathot, Ron A. A.; Quaedackers, Monique E.; Vulto, Arnold G.; Weimar, Willem; van Gelder, Teun

    2009-01-01

    Measurement of the pharmacodynamic biomarker inosine monophosphate dehydrogenase (IMPDH) activity in renal transplant recipients has been proposed to reflect the biological effect better than using pharmacokinetic parameters to monitor mycophenolate mofetil therapy. The IMPDH assays are however

  13. Diethylenetriaminepentaacetic acid-gadolinium (DTPA-Gd)-conjugated polysuccinimide derivatives as magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Lee, Ha Young; Jee, Hye Won; Seo, Sung Mi; Kwak, Byung Kook; Khang, Gilson; Cho, Sun Hang

    2006-01-01

    Biocompatible polysuccinimide (PSI) derivatives conjugated with diethylenetriaminepentaacetic acid gadolinium (DTPA-Gd) were prepared as magnetic resonance imaging (MRI) contrast agents. In this study, we synthesized PSI derivatives incorporating methoxy-poly(ethylene glycol) (mPEG) as hydrophilic ligand, hexadecylamine as hydrophobic ligand, and DTPA-Gd as contrast agent. PSI was synthesized by the polycondensation polymerization of aspartic acid. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Critical micellization concentrations were determined using fluorescent probes (pyrene). Micelle size and shape were measured by electro-photometer light scattering (ELS) and atomic force microscopy (AFM). The formed micelle size ranged from 100 to 300 nm. The T1-weighted MR images of the phantom prepared with PSI-mPEG-C16-(DTPA-Gd) were obtained in a 3.0 T clinical MR imager, and the conjugates showed a great potential as MRI contrast agents.

  14. Solution of Azelaic Acid (20%, Resorcinol (10% and Phytic Acid (6% Versus Glycolic Acid (50% Peeling Agent in the Treatment of Female Patients with Facial Melasma

    Directory of Open Access Journals (Sweden)

    Gita Faghihi

    2017-01-01

    Full Text Available Background: Melasma, a common acquired disorder of hyperpigmentation, especially in women, is often resistant to therapy. This study was aimed to evaluate the efficacy and safety of azelaic acid, resorcinol and phytic acid solution in chemical peeling of melasma in comparison to 50% glycolic acid. Materials and Methods: This clinical trial was performed, on 42 female patients with bilateral melasma. Severity of melasma was assessed by melasma area and severity index (MASI. Combination of (20% azelaic acid + 10% resorcinol + 6% phytic acid was used as a new peeling agent on the right side of the face and 50% glycolic acid on the left side every 2 weeks for 6 times. Follow-up was carried out for 3 months after the last session. Any decrease in MASI score and unwanted complications following peeling were evaluated and compared during the trial. Results: Patients showed marked improvement as calculated with MASI score before and after treatment in both sides of the face. The efficacy of combination formula (azelaic acid, resorcinol and phytic acid was similar to glycolic acid, but with fewer complications. There was no statistically difference in improvement between two groups (P > 0.05. However, the patient's discomfort following procedures was significantly lower with azelaic acid, resorcinol and phytic compared with the glycolic acid peels (P < 0.05 and there was the same duration in the beginning of the therapeutic response in both groups. Conclusion: Results showed that triple-combination was found to be an effective and safe peeling agent in the treatment of melasma and it was as effective as 50% glycolic acid peel.

  15. Effect of carboxylic acids as compatibilizer agent on mechanical properties of thermoplastic starch and polypropylene blends.

    Science.gov (United States)

    Martins, Andréa Bercini; Santana, Ruth Marlene Campomanes

    2016-01-01

    In this work, polypropylene/thermoplastic starch (PP/TPS) blends were prepared as an alternative material to use in disposable packaging, reducing the negative polymeric environmental impact. Unfortunately, this material displays morphological characteristics typical of immiscible polymer blends and a compatibilizer agent is needed. Three different carboxyl acids: myristic (C14), palmitic (C16) and stearic acids (C18) were used as natural compatibilizer agent (NCA). The effects of NCA on the mechanical, physical, thermal and morphological properties of PP/TPS blends were investigated and compared against PP/TPS with and without PP-grafted maleic anhydride (PPgMA). When compared to PP/TPS, blends with C18, PPgMA and C14 presented an improvement of 25, 22 and 17% in tensile strength at break and of 180, 194 and 259% in elongation at break, respectively. The highest increase, 54%, in the impact strength was achieved with C14 incorporation. Improvements could be seen, through scanning electron microscopy (SEM) images, in the compatibility between the immiscible components by acids incorporation. These results showed that carboxylic acids, specifically C14, could be used as compatibilizer agent and could substitute PPgMA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. Mycophenolate Mofetil for the Treatment of Multiple Sclerosis-associated Uveitis.

    Science.gov (United States)

    Hedayatfar, Alireza; Falavarjani, Khalil Ghasemi; Soheilian, Masoud; Elmi Sadr, Navid; Modarres, Mehdi; Parvaresh, Mohammad Mehdi; Naseripour, Masood; Rohani, Mohammad; Almasi, Mostafa; Chee, Soon-Phaik

    2017-06-01

    To report the efficacy of mycophenolate mofetil (MMF) as adjunctive therapy for the treatment of multiple sclerosis (MS)-associated uveitis. In this retrospective, interventional case series, patients with MS-associated uveitis who were treated by MMF as an adjunct therapy to systemic corticosteroid were studied. Patients' demographics, clinical course, response to treatment, and complications were assessed. A total of 30 eyes of 15 patients with a mean age of 34.5 ± 8.3 years were studied. In three patients (20%), onset of uveitis preceded the diagnosis of MS. The course of MS was relapsing-remitting in 11 patients (73.3%) and secondary progressive in four patients (26.7%). At 1 year after institution of MMF, all the patients were on oral prednisolone ≤ 7.5 mg/day, all eyes were quiet without macular edema, and 53.3% of eyes gained visual improvement. Supplemental periocular and intraocular injections were needed during the first 6 months after starting MMF therapy. The systemic adverse effects were transient and minor in severity. MMF had beneficial effects on vision and intraocular inflammation with an acceptable safety profile.

  17. Validated, Ultra Violet Spectroscopy method for the Dissolution study of Mycophenolate mofetil immediate release 500mg tablets

    OpenAIRE

    Surajpal P. Verma; Ozair Alam; Pooja Mullick; Nadeem Siddiqui; Suroor A. Khan

    2008-01-01

    A simple, selective and precise dissolution method was developed and validated for the Mycophenolate mofetil immediate release tablets. The method employed dissolution medium 0.1N HCl (pH1.2) and volume 900ml with USP-II apparatus (Paddle). Detection was made by measuring the absorbance on UV at the [lambda]~max~ 250nm. The method show the linearity in the range of conc. 5[micro]g/ml to 40[micro]g/ml with r^2^=0.999. The method is also validated as per International Conference of Harmonizatio...

  18. Oxalic acid as an assisting agent for the electrodialytic remediation of chromated copper arsenate treated timber waste

    DEFF Research Database (Denmark)

    Ribeiro, Alexandra B.; Mateus, Eduardo P.; Ottosen, Lisbeth M.

    1999-01-01

    The electrodialytic process is proposed as a technique for the remediation of chromated copper arsenate treated timber waste, using oxalic acid as assisting agent. The method prowed succesfull 93% Cu, 95% Cr and 99% As was removed from the timber.......The electrodialytic process is proposed as a technique for the remediation of chromated copper arsenate treated timber waste, using oxalic acid as assisting agent. The method prowed succesfull 93% Cu, 95% Cr and 99% As was removed from the timber....

  19. Quantitative structure-property relationship (correlation analysis) of phosphonic acid-based chelates in design of MRI contrast agent.

    Science.gov (United States)

    Tiwari, Anjani K; Ojha, Himanshu; Kaul, Ankur; Dutta, Anupama; Srivastava, Pooja; Shukla, Gauri; Srivastava, Rakesh; Mishra, Anil K

    2009-07-01

    Nuclear magnetic resonance imaging is a very useful tool in modern medical diagnostics, especially when gadolinium (III)-based contrast agents are administered to the patient with the aim of increasing the image contrast between normal and diseased tissues. With the use of soft modelling techniques such as quantitative structure-activity relationship/quantitative structure-property relationship after a suitable description of their molecular structure, we have studied a series of phosphonic acid for designing new MRI contrast agent. Quantitative structure-property relationship studies with multiple linear regression analysis were applied to find correlation between different calculated molecular descriptors of the phosphonic acid-based chelating agent and their stability constants. The final quantitative structure-property relationship mathematical models were found as--quantitative structure-property relationship Model for phosphonic acid series (Model 1)--log K(ML) = {5.00243(+/-0.7102)}- MR {0.0263(+/-0.540)}n = 12 l r l = 0.942 s = 0.183 F = 99.165 quantitative structure-property relationship Model for phosphonic acid series (Model 2)--log K(ML) = {5.06280(+/-0.3418)}- MR {0.0252(+/- .198)}n = 12 l r l = 0.956 s = 0.186 F = 99.256.

  20. New, well-retained myocardial imaging agent: radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid

    International Nuclear Information System (INIS)

    Goodman, M.M.; Knapp, F.F. Jr.; Callahan, A.P.; Ferren, L.A.

    1982-01-01

    A method involving the acid-catalyzed decomposition of a piperidyltriazene intermediate in the presence of radioiodide has been developed for the synthesis of radioiodinated 15-(p-iodophenyl)-6-tellurapentadecanoic acid. The iodine-125-labeled agent shows rapid, pronounced myocardial uptake in rats (5.30-6.45% injected dose/g after 5 min) and also exhibits the prolonged retention previously observed with 9-[/sup 123m/Te]telluraheptadecanoic acid (9-[/sup 123m/Te]HDA). After 6 hr, the heart uptake remained high (3.89-5.33% dose/g) and decreased only to 3.02-3.41% dose/g after 24 hr. Very low blood activity was detected (0.24-0.27% dose/g at 5 min; 0.29-0.32% dose/g at 6 hr) and the heart-to-blood ratios were high (22:1 at 5 min; 15:1 at 6 hr). Minimal deiodination was demonstrated by the low thyroid uptake (1.41-1.63% dose/g at 5 min; 5.33-7.08% dose/g at 6 hr). The rapid and pronounced uptake, prolonged myocardial retention, and low in vivo deiodination make this agent attractive for further evaluation

  1. [Effects of tooth whitening agents and acidic drinks on the surface properties of dental enamel].

    Science.gov (United States)

    Chen, Xiaoling; Chen, Zhiqun; Lin, Yao; Shao, Jinquan; Yin, Lu

    2013-10-01

    Using tooth whitening agents (bleaching clip) in vitro and acidic drinks, we conducted a comparative study of the changes in enamel surface morphology, Ca/P content, and hardness. Tooth whitening glue pieces, cola, and orange juice were used to soak teeth in artificial saliva in vitro. Physiological saline was used as a control treatment. The morphology of the four groups was observed under a scanning electron microscope (SEM) immediately after the teeth were soaked for 7 and 14 d. The changes in Ca/P content and microhardness were analyzed. The enamel surfaces of the teeth in the three test groups were demineralized. The Ca/P ratio and the average microhardness were significantly lower than those of the control group immediately after the teeth were soaked (P 0.05). Bleaching agents caused transient demineralization of human enamel, but these agents could induce re-mineralization and repair of enamel over time. Demineralization caused by bleaching covered a relatively normal range compared with acidic drinks and daily drinking.

  2. Synthesis of 3-O-propargylated betulinic acid and its 1,2,3-triazoles as potential apoptotic agents

    DEFF Research Database (Denmark)

    Majeed, Rabiya; Sangwan, Payare L; Chinthakindi, Praveen K

    2013-01-01

    Cytotoxic agents from nature are presently the mainstay of anticancer chemotherapy, and the need to reinforce the arsenal of anticancer agents is highly desired. Chemical transformation studies carried out on betulinic acid, through concise 1,2,3-triazole synthesis via click chemistry approach at...

  3. De novo Renal Transplantation after Kaposi Sarcoma: Favorable Outcome in a Patient Receiving Sirolimus and Mycophenolate-Based Immunosuppression

    Directory of Open Access Journals (Sweden)

    F. Friedersdorff

    2010-04-01

    Full Text Available Immunosuppressive treatment increases the risk of infection and malignancy in organ transplant recipients. We report on a 42-year-old male renal transplant recipient who lost his first graft after reduction of immunosuppressive treatment due to Kaposi sarcoma and who successfully underwent a second renal transplant 10 years later. The patient’s current treatment consists of low-dose prednisone, and the two antiproliferative immunosuppressants mycophenolate mofetil and rapamycin. 4.5 years after his second transplant, the serum creatinine is 1 mg/dl and the patient has no signs of recurrent disease.

  4. Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound

    Directory of Open Access Journals (Sweden)

    Davide Viggiano

    2018-04-01

    Full Text Available Current urate-lowering therapy (ULT includes three direct acting drugs (allopurinol, febuxostat, Rasburicase and at least four ‘indirect’ drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer. Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis, the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels.

  5. Inhibition of Erwinia chrysanthemi growth to different concentrations of folic acid: possible use of folic acid as bacteriostatic agent and fortifying of Solanum tuberosum potato

    Directory of Open Access Journals (Sweden)

    Andrea Marcelo Correa

    2017-05-01

    Full Text Available Introduction:The enterobacteria of the Erwinia spp genus produce disease in potatoes, which is a tuber of mass consumption. The regulation of DNA methylation can regulate the proliferation of Erwinia in such a way that the concentrations of folic acid may have an effect on the microorganism pathogenic ability. On the other hand, the folic acid prevents the appearance of neural tube defects in humans. Objective: To evaluate folic acid as a bacteriostatic agent of Erwinia and, at the same time, as part of the fortification of mass consumption food such as the potatoes. Materials and methods: The biochemical characterization of the Erwinia chrysanthemi was carried out and its growth compared to different concentrations of folic acid was studied. Results: When increasing the concentrations of the vitamin from 0.3 µg/L up to 6.8 µg/L, the bacterial growth of Erwinia chrysanthemi is inhibited. The vitamin inhibits the growth in cultivation of Erwinia chrysanthemi and acts as a bacteriostatic agent. This aspect is of great importance given that, theoretically, if potatoes were fortified with micro-nutrient, this would act against the infectious agent and, at the same time, contribute to the adequate intake of the vitamin in the general population.

  6. Uranium accumulation in Brassica rapa L. and effect of citric acid and humic acids as chelating agents

    International Nuclear Information System (INIS)

    Lopez del R, H.; Perez C, G. A.; Davila R, J. I.; Mireles G, F.; Rodriguez H, G.

    2016-09-01

    Phyto extraction is a technique that makes use of plants for the remediation of soils contaminated with heavy metals. In this study the uranium incorporation in the Brassica rapa L. species was evaluated, in artificially contaminated inert soils with 40 mg U/kg, and the effect of adding of the natural chelating agents citric acid and humic acids in the accumulation of uranium was analyzed. Soil free of organic matter and biologically inert was obtained by controlled calcination s of natural soil. Cultures in the prepared soil consisted of five growth treatments: 1) cultivation without uranium or additives; 2) cultivation in the uranium presence; 3) cultivation with uranium and citric acid (2 g/kg); 4) cultivation with uranium and humic acids (10 g/kg); 5) uranium cultivation and combination of citric and humic acids at the same concentrations. There was no adverse effect on plant growth with the presence of uranium at the given concentration. Regarding the controls, the total biomass in the presence of uranium was slightly higher, while the addition of humic acids significantly stimulated the production of biomass with respect to the citric acid. The combined action of organic acids produced the highest amount of biomass. The efficiency of phyto extraction followed the order Humic acids (301 μg U/g) > Non-assisted (224 μg U/g) >> Citric acid + Humic acids (68 μg U/g) > Citric acid (59 μg U/g). The values of uranium concentration in the total biomass show that the species Brassica rapa L. has the capacity of phyto extraction of uranium in contaminated soils. The addition of humic acids increases the uranium extraction while the addition of citric acid disadvantages it. (Author)

  7. Study of photo-oxidative reactivity of sunscreening agents based on photo-oxidation of uric acid by kinetic Monte Carlo simulation

    International Nuclear Information System (INIS)

    Moradmand Jalali, Hamed; Bashiri, Hadis; Rasa, Hossein

    2015-01-01

    In the present study, the mechanism of free radical production by light-reflective agents in sunscreens (TiO 2 , ZnO and ZrO 2 ) was obtained by applying kinetic Monte Carlo simulation. The values of the rate constants for each step of the suggested mechanism have been obtained by simulation. The effect of the initial concentration of mineral oxides and uric acid on the rate of uric acid photo-oxidation by irradiation of some sun care agents has been studied. The kinetic Monte Carlo simulation results agree qualitatively with the existing experimental data for the production of free radicals by sun care agents. - Highlights: • The mechanism and kinetics of uric acid photo-oxidation by irradiation of sun care agents has been obtained by simulation. • The mechanism has been used for free radical production of TiO 2 (rutile and anatase), ZnO and ZrO 2 . • The ratios of photo-activity of ZnO to anastase, rutile and ZrO have been obtained. • By doubling the initial concentrations of mineral oxide, the rate of reaction was doubled. • The optimum ratio of initial concentration of mineral oxides to uric acid has been obtained

  8. Mixtures of Quaternary Ammonium Compounds and Long-chain Fatty Acids as Antifungal Agents

    Science.gov (United States)

    Kull, F. C.; Eisman, P. C.; Sylwestrowicz, H. D.; Mayer, R. L.

    1961-01-01

    The influence of undecylenic acid on the fungistatic effect of phenoxyethyldimethyldodecylammonium bromide (Domiphen bromide) against Trichophyton mentagrophytes was investigated. The unsaturated fatty acid was found to enhance the fungistatic activity of Domiphen bromide against this organism. The ratio of concentrations of these agents has a marked influence on the results of in vitro tests for antifungal action resulting in a completely different effect than heretofore noted in combination experiments against bacteria. The enhancing phenomenon is not particular to T. mentagrophytes, it was observed also with Candida albicans. PMID:14460466

  9. Stable agents for imaging investigations

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    This invention concerns highly stable compounds useful in preparing technetium 99m based scintiscanning exploration agents. The compounds of this invention include a pertechnetate reducing agent or a solution of oxidized pertechnetate and an efficient proportion, sufficient to stabilize the compounds in the presence of oxygen and of radiolysis products, of ascorbic acid or a pharmaceutically acceptable salt or ester of this acid. The invention also concerns a perfected process for preparing a technetium based exploration agent, consisting in codissolving the ascorbic acid or a pharmaceutically acceptable salt or ester of such an acid and a pertechnetate reducing agent in a solution of oxidized pertechnetate [fr

  10. Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents.

    Science.gov (United States)

    Apfel, C; Banner, D W; Bur, D; Dietz, M; Hirata, T; Hubschwerlen, C; Locher, H; Page, M G; Pirson, W; Rossé, G; Specklin, J L

    2000-06-15

    Low-molecular-weight beta-sulfonyl- and beta-sulfinylhydroxamic acid derivatives have been synthesized and found to be potent inhibitors of Escherichia coli peptide deformylase (PDF). Most of the compounds synthesized and tested displayed antibacterial activities that cover several pathogens found in respiratory tract infections, including Chlamydia pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The potential of these compounds as antibacterial agents is discussed with respect to selectivity, intracellular concentrations in bacteria, and potential for resistance development.

  11. Occurrence of immunosuppressive drugs and their metabolites in the sewage-impacted Vistula and Utrata Rivers and in tap water from the Warsaw region (Poland).

    Science.gov (United States)

    Giebułtowicz, Joanna; Nałęcz-Jawecki, Grzegorz

    2016-04-01

    Immunosuppresive therapy following organ transplant frequently includes treatment with tacrolimus and mycophenolic acid derivatives. These pharmaceuticals may enter the environment through wastewater treatment plant (WWTP) effluents and may have a potentially harmful effect on aquatic biota. Tacrolimus, mycophenolic acid and their metabolites were measured at specific points of a large Polish river (Vistula), a smaller river (Utrata) and in tap water samples from the Warsaw region. Analysis was performed using liquid chromatography tandem mass spectrometry, after solid phase extraction for water samples, or QuEChERS extraction for sediments. Residues of tacrolimus were below quantitation limits in both water and sediment samples. However, in water samples mycophenolic acid concentrations were measured at up to 180 ng L(-1) downstream of WWTP outfalls. No immunosuppressive drugs were detected in tap water. Concentrations of mycophenolic acid exceeded the predicted no effect concentration (PNEC) value in some Polish surface water, and risk calculations predicted at least twice higher concentrations in some other countries of the European Union. To the best of the authors' knowledge, this is the first report of these immunosuppressive drug concentrations in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Radiographic scanning agent

    International Nuclear Information System (INIS)

    Tofe, A.J.

    1976-01-01

    A stable radiographic scanning agent on a sup(99m)Tc basis has been developed. The substance contains a pertechnetate reduction agent, tin(II)-chloride, chromium(II)-chloride, or iron(II)-sulphate, as well as an organospecific carrier and ascorbic acid or a pharmacologically admissible salt or ester of ascorbic acid. (VJ) [de

  13. Selective complexometric determination of titanium(IV) using sodium potassium tartrate or ascorbic acid as masking agent

    International Nuclear Information System (INIS)

    Sreekumar, N.V.; Bhat, N.G.; Narayana, B.; Nazareth, R.A.; Hegde, P.; Manjunatha, B.R.

    2003-01-01

    A simple, rapid and accurate complexometric method is proposed for the determination of titanium(IV) where sodium potassium tartrate or ascorbic acid were used as masking agents. In the presence of diverse metal ions, titanium is first complexed with excess of EDTA and surplus EDTA is then titrated at pH 5-6 with zinc sulfate, xylenol orange being used as indicator. An excess of 5 % aqueous sodium potassium tartrate is then added to displace the complexed EDTA from the Ti-EDTA complex quantitatively, which is titrated with zinc sulfate. Also, ascorbic acid may be used as the releasing agent. The methods work well in the range 1-53 mg of Ti(IV) for sodium potassium tartrate with relative errors ± 0.28 % and standard deviations 0.16 mg. For ascorbic acid the range is 1.00-30.00 mg of Ti(IV) with relative errors of ± 0.40 % and standard deviations of 0.05 mg. (author)

  14. Study of photo-oxidative reactivity of sunscreening agents based on photo-oxidation of uric acid by kinetic Monte Carlo simulation

    Energy Technology Data Exchange (ETDEWEB)

    Moradmand Jalali, Hamed; Bashiri, Hadis, E-mail: hbashiri@kashanu.ac.ir; Rasa, Hossein

    2015-05-01

    In the present study, the mechanism of free radical production by light-reflective agents in sunscreens (TiO{sub 2}, ZnO and ZrO{sub 2}) was obtained by applying kinetic Monte Carlo simulation. The values of the rate constants for each step of the suggested mechanism have been obtained by simulation. The effect of the initial concentration of mineral oxides and uric acid on the rate of uric acid photo-oxidation by irradiation of some sun care agents has been studied. The kinetic Monte Carlo simulation results agree qualitatively with the existing experimental data for the production of free radicals by sun care agents. - Highlights: • The mechanism and kinetics of uric acid photo-oxidation by irradiation of sun care agents has been obtained by simulation. • The mechanism has been used for free radical production of TiO{sub 2} (rutile and anatase), ZnO and ZrO{sub 2}. • The ratios of photo-activity of ZnO to anastase, rutile and ZrO have been obtained. • By doubling the initial concentrations of mineral oxide, the rate of reaction was doubled. • The optimum ratio of initial concentration of mineral oxides to uric acid has been obtained.

  15. Investigating the use of coupling agents to improve the interfacial properties between a resorbable phosphate glass and polylactic acid matrix.

    Science.gov (United States)

    Hasan, Muhammad Sami; Ahmed, Ifty; Parsons, Andrew J; Rudd, Chris D; Walker, Gavin S; Scotchford, Colin A

    2013-09-01

    Eight different chemicals were investigated as potential candidate coupling agents for phosphate glass fibre reinforced polylactic acid composites. Evidence of reaction of the coupling agents with phosphate glass and their effect on surface wettability and glass degradation were studied along with their principle role of improving the interface between glass reinforcement and polymer matrix. It was found that, with an optimal amount of coupling agent on the surface of the glass/polymer, interfacial shear strength improved by a factor of 5. Evidence of covalent bonding between agent and glass was found for three of the coupling agents investigated, namely: 3-aminopropyltriethoxysilane; etidronic acid and hexamethylene diisocyanate. These three coupling agents also improved the interfacial shear strength and increased the hydrophobicity of the glass surface. It is expected that this would provide an improvement in the macroscopic properties of full-scale composites fabricated from the same materials which may also help to retain these properties for the desired length of time by retarding the breakdown of the fibre/matrix interface within these composites.

  16. [Enhanced phytoextraction of heavy metal contaminated soil by chelating agents and auxin indole-3-acetic acid].

    Science.gov (United States)

    Zhou, Jian-min; Dang, Zhi; Chen, Neng-chang; Xu, Sheng-guang; Xie, Zhi-yi

    2007-09-01

    The environmental risk of chelating agents such as EDTA application to the heavy metals polluted soils and the stress on plant roots due to the abrupt increase metals concentration limit the wide commercial use of chelate-induced phytoextraction. Chelating agent ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) and auxin indole-3-acetic acid (IAA) were used for enhancing heavy metals uptake from soils by Zea mays L. (corn) in pot experiments. The metals content in plant tissues was quantified using an inductively coupled plasma mass spectrometer (ICP-MS). The results showed that the combination of IAA and EDTA increased the biomass by about 40.0% and the contents of Cu, Zn, Cd and Pb in corn shoots by 27.0%, 26.8%, 27.5% and 32.8% respectively, as compared to those in EDTA treatment. While NTA&IAA treatment increased the biomass by about 29.9% and the contents of Cu, Zn, Cd and Pb in corn shoots by 31.8%, 27.6%, 17.0% and 26.9% respectively, as compared to those in NTA treatment. These results indicated that corn growth was promoted, and the biomass and the accumulation of heavy metals in plant shoots were increased significantly with the addition of IAA, which probably helps to change the cell membrane properties and the biomass distribution, resulting in the alleviation of the phytotoxicity of metals and the chelating agents.

  17. The impact of everolimus versus mycophenolate on blood and lymphocyte cyclosporine exposure in heart-transplant recipients

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Barth, David; Delgado, Diego H

    2009-01-01

    CsA C2 levels and blood CsA AUC(0-12) in groups of patients treated with MMF or everolimus (R(2) 0.93 and 0.96, respectively; P 2) = 0.98), there was poor correlation...... between whole-blood C2 and lymphocyte AUC(0-12) in patients treated with everolimus (R(2) = 0.24). CONCLUSION: Standard blood CsA levels accurately predict intralymphocytic exposure to CsA in patients concomitantly treated with MMF but not in patients treated with everolimus........ METHODS: Twelve-hour pharmacokinetic studies of whole-blood and intralymphocytic CsA concentrations were conducted in long-term heart-transplant recipients treated with mycophenolate mofetil (MMF) + CsA (n = 8) and everolimus + CsA (n = 9). RESULTS: There was a highly significant correlation between blood...

  18. Urate-Lowering Agents in Asymptomatic Hyperuricemia: Role of Urine Sediment Analysis and Musculoskeletal Ultrasound.

    Science.gov (United States)

    Viggiano, Davide; Gigliotti, Giuseppe; Vallone, Gianfranco; Giammarino, Anna; Nigro, Michelangelo; Capasso, Giovambattista

    2018-01-01

    Current urate-lowering therapy (ULT) includes three direct acting drugs (allopurinol, febuxostat, Rasburicase) and at least four 'indirect' drugs with other important targets (canagliflozin, losartan, fenofibrate and sevelamer). Moreover, the alcalinization of urines using bicarbonate can be used to dissolve urate crystals and the clinician may discontinue several drugs are known to increase serum levels of uric acid, such as diuretics, aspirin, cyclosporine, theophylline, mycophenolate and ACE inhibitors. While there is a consensus to start ULT in cases of symptomatic hyperuricemia (gout, urate-nephrolithiasis), the very frequent conditions of asymptomatic hyperuricemia remains a major conundrum. The effect of asymptomatic hyperuricemia on kidney function has had fluctuating positions over decades. The conflicting results might indicate: (i) the presence of counterbalancing positive and negative effects on kidney function of both serum uric acid and urate-lowering agents, (ii) the presence of a subpopulation of patients, as yet unidentified, which could truly benefit from a urate-lowering therapy. Therefore, today the treatment of asymptomatic hyperuricemia is not recommended nor excluded by current guidelines. Here we suggest that a possible guide for the treatment of asymptomatic hyperuricemia might be the presence of urate crystals in the urine sediment and/or signs of asymptomatic articular damage by urates, identified by musculo-skeletal ultrasound. Moreover, a watchful analysis of the trend in creatinine/eGFR, proteinuria or urate levels might also guide the clinician. Initiation of ULT and follow-up in cases of asymptomatic hyperuricemia should consider urine sediment analysis, musculoskeletal ultrasound and trends in creatinine, proteinuria and serum urate levels. © 2018 The Author(s). Published by S. Karger AG, Basel.

  19. Study of photo-oxidative reactivity of sunscreening agents based on photo-oxidation of uric acid by kinetic Monte Carlo simulation.

    Science.gov (United States)

    Moradmand Jalali, Hamed; Bashiri, Hadis; Rasa, Hossein

    2015-05-01

    In the present study, the mechanism of free radical production by light-reflective agents in sunscreens (TiO2, ZnO and ZrO2) was obtained by applying kinetic Monte Carlo simulation. The values of the rate constants for each step of the suggested mechanism have been obtained by simulation. The effect of the initial concentration of mineral oxides and uric acid on the rate of uric acid photo-oxidation by irradiation of some sun care agents has been studied. The kinetic Monte Carlo simulation results agree qualitatively with the existing experimental data for the production of free radicals by sun care agents. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Synthesis, characterization and biological evaluation of bile acid-aromatic/heteroaromatic amides linked via amino acids as anti-cancer agents.

    Science.gov (United States)

    Agarwal, Devesh S; Anantaraju, Hasitha Shilpa; Sriram, Dharmarajan; Yogeeswari, Perumal; Nanjegowda, Shankara H; Mallu, P; Sakhuja, Rajeev

    2016-03-01

    A series of bile acid (Cholic acid and Deoxycholic acid) aryl/heteroaryl amides linked via α-amino acid were synthesized and tested against 3 human cancer cell-lines (HT29, MDAMB231, U87MG) and 1 human normal cell line (HEK293T). Some of the conjugates showed promising results to be new anticancer agents with good in vitro results. More specifically, Cholic acid derivatives 6a (1.35 μM), 6c (1.41 μM) and 6m (4.52 μM) possessing phenyl, benzothiazole and 4-methylphenyl groups showed fairly good activity against the breast cancer cell line with respect to Cisplatin (7.21 μM) and comparable with respect to Doxorubicin (1 μM), while 6e (2.49μM), 6i (2.46 μM) and 6m (1.62 μM) showed better activity against glioblastoma cancer cell line with respect to both Cisplatin (2.60 μM) and Doxorubicin (3.78 μM) drugs used as standards. Greater than 65% of the compounds were found to be safer on human normal cell line. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Development of superior bone scintigraphic agent from a series of {sup 99m}Tc-labeled zoledronic acid derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jianguo [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Qiu Ling, E-mail: qiulingwx@gmail.com [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Cheng Wen [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Luo Shineng, E-mail: shineng914@yahoo.com.cn [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China); Xue Li; Zhang Shu [Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063 (China)

    2012-05-15

    Two novel zoledronic acid (ZL) derivatives, 1-hydroxy-4-(1H-imidazol-1-yl)butane-1,1-diyldiphosphonic acid (IBDP) and 1-hydroxy-5-(1H-imidazol-1-yl)pentane-1,1-diyldiphosphonic acid (IPeDP), were prepared and labeled with the radionuclide technetium-99m in a high labeling yield. In vitro stabilities of these radiolabeled complexes were measured by the radio-HPLC analysis as a function of time, which showed excellent stability with the radiochemical purity of over 95% at 6 h post preparation. Their in vivo biological performances were evaluated and compared with those of {sup 99m}Tc-ZL and {sup 99m}Tc-MDP (methylenediphosphonic acid). The biodistribution in mice and scintigraphic images of the rabbit showed that the tracer agent {sup 99m}Tc-IPeDP had highly selective uptake in the skeletal system and rapid clearance from the blood and soft tissues and an excellent scintigraphic image can be obtained in a shorter time post injection with clear visualization of the skeleton and low soft tissue activity. These preclinical studies suggest that {sup 99m}Tc-IPeDP would be a novel superior bone scintigraphic agent. - Highlights: Black-Right-Pointing-Pointer Two novel diphosphonic acids were labeled with the {sup 99m}Tc in high labeling yield. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP had high uptake in skeletal system and rapid clearance from blood. Black-Right-Pointing-Pointer {sup 99m}Tc-IPeDP reveals attractive biological features as superior bone scanning agent.

  2. The effect of simulated acid rain on the stabilization of cadmium in contaminated agricultural soils treated with stabilizing agents.

    Science.gov (United States)

    Zhu, Hao; Wu, Chunfa; Wang, Jun; Zhang, Xumei

    2018-04-16

    Stabilization technology is one of widely used remediation technologies for cadmium (Cd)-contaminated agricultural soils, but stabilized Cd in soil may be activated again when external conditions such as acid rain occurred. Therefore, it is necessary to study the effect of acid rain on the performance of different stabilizing agents on Cd-polluted agriculture soils. In this study, Cd-contaminated soils were treated with mono-calcium phosphate (MCP), mono-ammonium phosphate (MAP), and artificial zeolite (AZ) respectively and incubated 3 months. These treatments were followed by two types of simulated acid rain (sulfuric acid rain and mixed acid rain) with three levels of acidity (pH = 3.0, 4.0, and 5.6). The chemical forms of Cd in the soils were determined by Tessier's sequential extraction procedure, and the leaching toxicities of Cd in the soils were assessed by toxicity characteristic leaching procedure (TCLP). The results show that the three stabilizing agents could decrease the mobility of Cd in soil to some degree with or without simulated acid rain (SAR) treatment. The stabilization performances followed the order of AZ stabilized soil, and both anion composition and pH of acid rain were two important factors that influenced the stabilization effect of Cd.

  3. Potential Use of Phenolic Acids as Anti-Candida Agents: A Review

    Science.gov (United States)

    Teodoro, Guilherme R.; Ellepola, Kassapa; Seneviratne, Chaminda J.; Koga-Ito, Cristiane Y.

    2015-01-01

    There has been a sharp rise in the occurrence of Candida infections and associated mortality over the last few years, due to the growing body of immunocompromised population. Limited number of currently available antifungal agents, undesirable side effects and toxicity, as well as emergence of resistant strains pose a considerable clinical challenge for the treatment of candidiasis. Therefore, molecules that derived from natural sources exhibiting considerable antifungal properties are a promising source for the development of novel anti-candidal therapy. Phenolic compounds isolated from natural sources possess antifungal properties of interest. Particularly, phenolic acids have shown promising in vitro and in vivo activity against Candida species. However, studies on their mechanism of action alone or in synergism with known antifungals are still scarce. This review attempts to discuss the potential use, proposed mechanisms of action and limitations of the phenolic acids in anti-candidal therapy. PMID:26733965

  4. Acute pancreatitis induced by mycophenolate mofetil in a kidney transplant patient

    Directory of Open Access Journals (Sweden)

    Einollahi Behzad

    2015-04-01

    Full Text Available Acute pancreatitis is a rare life-threatening complication in patients after kidney transplantation. Here we described a 56-year-old man who had received a living related kidney transplant for an end-stage renal disease. In his regular follow-up, his serum creatinine was gradually increased and he underwent an allograft biopsy, which revealed an interstitial nephritis/tubular atrophy grade II. Mycophenolate mofetil (MMF was prescribed to control chronic allograft nephropathy. He presented with complaints of severe abdominal pain, vomiting, loss of appetite and fever requiring hospital admission twelve days later. Acute pancreatitis was diagnosed on the basis of laboratory data and imaging findings during hospital admission. There was no history of alcohol consumption in our patient. Unfortunately he died one week later and autopsy findings demonstrated acute necrotizing pancreatitis. The bladder drainage of this patients was normal. Laboratory findings in this patient did not endorse infections and other possibilities regarding the etiology of acute pancreatitis in this patient. Therefore, we concluded that acute pancreatitis in near the patient was induced by drugs and basis on our evidence, MMF is the most important suspect. This study suggests that acute pancreatitis can be considered as a side effect of MMF.

  5. Data of thermal degradation and dynamic mechanical properties of starch-glycerol based films with citric acid as crosslinking agent.

    Science.gov (United States)

    González Seligra, Paula; Medina Jaramillo, Carolina; Famá, Lucía; Goyanes, Silvia

    2016-06-01

    Interest in biodegradable edible films as packaging or coating has increased because their beneficial effects on foods. In particular, food products are highly dependents on thermal stability, integrity and transition process temperatures of the packaging. The present work describes a complete data of the thermal degradation and dynamic mechanical properties of starch-glycerol based films with citric acid (CA) as crosslinking agent described in the article titled: "Biodegradable and non-retrogradable eco-films based on starch-glycerol with citric acid as crosslinking agent" González Seligra et al. (2016) [1]. Data describes thermogravimetric and dynamical mechanical experiences and provides the figures of weight loss and loss tangent of the films as a function of the temperature.

  6. New method for studying the efficiency of chelating agents of the polyamine acid series for internal decontamination

    International Nuclear Information System (INIS)

    Lafuma, J.; Nenot, J.C.; Morin, M.

    1968-01-01

    We followed the biological fate of a complex formed on one side with either a rare earth (cerium-144) or a transuranium element (plutonium-239), and on the other side with a chelating agent of the polyamino acid series (EDTA, BAETA, DTPA, TTHA). This method allowed to study: 1 - the in vivo stability of the various complexes and to compare them; 2 - the stability of the complexes as a function of the isotope - chelating agent weight relationships; 3 - the metabolism of the chelating agents resulting in stable complexes, i. e. DTPA and TTHA mainly. This simple method brought out the higher efficiency, of DTPA in chelating rare earths and plutonium and for therapeutic purposes. (authors) [fr

  7. RNA preservation agents and nucleic acid extraction method bias perceived bacterial community composition.

    Directory of Open Access Journals (Sweden)

    Ann McCarthy

    Full Text Available Bias is a pervasive problem when characterizing microbial communities. An important source is the difference in lysis efficiencies of different populations, which vary depending on the extraction protocol used. To avoid such biases impacting comparisons between gene and transcript abundances in the environment, the use of one protocol that simultaneously extracts both types of nucleic acids from microbial community samples has gained popularity. However, knowledge regarding tradeoffs to combined nucleic acid extraction protocols is limited, particularly regarding yield and biases in the observed community composition. Here, we evaluated a commercially available protocol for simultaneous extraction of DNA and RNA, which we adapted for freshwater microbial community samples that were collected on filters. DNA and RNA yields were comparable to other commonly used, but independent DNA and RNA extraction protocols. RNA protection agents benefited RNA quality, but decreased DNA yields significantly. Choice of extraction protocol influenced the perceived bacterial community composition, with strong method-dependent biases observed for specific phyla such as the Verrucomicrobia. The combined DNA/RNA extraction protocol detected significantly higher levels of Verrucomicrobia than the other protocols, and those higher numbers were confirmed by microscopic analysis. Use of RNA protection agents as well as independent sequencing runs caused a significant shift in community composition as well, albeit smaller than the shift caused by using different extraction protocols. Despite methodological biases, sample origin was the strongest determinant of community composition. However, when the abundance of specific phylogenetic groups is of interest, researchers need to be aware of the biases their methods introduce. This is particularly relevant if different methods are used for DNA and RNA extraction, in addition to using RNA protection agents only for RNA

  8. Synergistic Effects of Nucleating Agents and Plasticizers on the Crystallization Behavior of Poly(lactic acid

    Directory of Open Access Journals (Sweden)

    Xuetao Shi

    2015-01-01

    Full Text Available The synergistic effect of nucleating agents and plasticizers on the thermal and mechanical performance of PLA nanocomposites was investigated with the objective of increasing the crystallinity and balancing the stiffness and toughness of PLA mechanical properties. Calcium carbonate, halloysite nanotubes, talc and LAK (sulfates were compared with each other as heterogeneous nucleating agents. Both the DSC isothermal and non-isothermal studies indicated that talc and LAK were the more effective nucleating agents among the selected fillers. Poly(D-lactic acid (PDLA acted also as a nucleating agent due to the formation of the PLA stereocomplex. The half crystallization time was reduced by the addition of talc to about 2 min from 37.5 min of pure PLA by the isothermal crystallization study. The dynamic mechanical thermal study (DMTA indicated that nanofillers acted as both reinforcement fillers and nucleating agents in relation to the higher storage modulus. The plasticized PLA studied by DMTA indicated a decreasing glass transition temperature with the increasing of the PEG content. The addition of nanofiller increased the Young’s modulus. PEG had the plasticization effect of increasing the break deformation, while sharply decreasing the stiffness and strength of PLA. The synergistic effect of nanofillers and plasticizer achieved the balance between stiffness and toughness with well-controlled crystallization.

  9. Mycophenolate mofetil in pediatric renal transplantation: A single center experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-01

    Raheem OA, Kamel MH, Daly PJ, Mohan P, Little DM, Awan A, Hickey DP. Mycophenolate mofetil in pediatric renal transplantation: A single center experience. Pediatr Transplantation 2011: 15:240-244. © 2009 John Wiley & Sons A\\/S. Abstract:  We assessed our long-term experience with regards to the safety and efficacy of MMF in our pediatric renal transplant population and compared it retrospectively to our previous non-MMF immunosuppressive regimen. Forty-seven pediatric renal transplants received MMF as part of their immunosuppressive protocol in the period from January 1997 till October 2006 (MMF group). A previously reported non-MMF group of 59 pediatric renal transplants was included for comparative analysis (non-MMF group). The MMF group comprised 29 boys and 18 girls, whereas the non-MMF group comprised 34 boys and 25 girls. Mean age was 11.7 and 12 yr in the MMF and non-MMF groups, respectively. The incidence of acute rejection episodes was 11 (23.4%) and 14 (24%) in the MMF and non-MMF group, respectively. Two (3.3%) grafts were lost in the non-MMF group compared with one (2.1%) in the MMF group. Twenty-one (44.68%) patients in the MMF group developed post-transplant infections compared with 12 (20.33%) in the non-MMF group (p < 0.0001). In conclusion, the use of MMF in pediatric renal transplantation was not associated with a lower rejection rate or immunological graft loss. It did, however, result in a significantly higher rate of viral infections.

  10. Fluid extraction using carbon dioxide and organophosphorus chelating agents

    Science.gov (United States)

    Smart, Neil G.; Wai, Chien M.; Lin, Yuehe; Kwang, Yak Hwa

    1998-01-01

    Methods for extracting metalloid and metal species from a solid or liquid material by exposing the material to a fluid solvent, particularly supercritical CO.sub.2, and a chelating agent are described. The chelating agent forms a chelate with the species, the chelate being soluble in the fluid to allow removal of the species from the material. In preferred embodiments the extraction solvent is supercritical CO.sub.2 and the chelating agent comprises an organophosphorous chelating agent, particularly sulfur-containing organophosphorous chelating agents, including mixtures of chelating agents. Examples of chelating agents include monothiophosphinic acid, di-thiophosphinic acid, phosphine sulfite, phosphorothioic acid, and mixtures thereof. The method provides an environmentally benign process for removing metal and metalloids from industrial waste solutions, particularly acidic solutions. Both the chelate and the supercritical fluid can be regenerated and the contaminant species recovered to provide an economic, efficient process.

  11. Radiographic scintiscanning agent

    International Nuclear Information System (INIS)

    Bevan, J.A.

    1979-01-01

    A new technetium-based scintiscanning agent has been prepared comprising a water soluble sup(99m)Tc-methanehydroxydiphosphonate in combination with a reducing agent selected from stannous, ferrous, chromous and titanous salts. As an additional stabilizer salts and esters of gentisic or ascorbic acids have been used. (E.G.)

  12. Lanthanum-doped mesostructured strontium titanates synthesized via sol–gel combustion route using citric acid as complexing agent

    Energy Technology Data Exchange (ETDEWEB)

    Sukpanish, Polthep [Department of Chemical Technology, Faculty of Science, Chulalongkorn University, Patumwan, Bangkok 10330 (Thailand); Center of Excellence on Petrochemical and Materials Technology (PETROMAT), Chulalongkorn University, Patumwan, Bangkok 10330 (Thailand); Lertpanyapornchai, Boontawee [Program in Petrochemistry, Faculty of Science, Chulalongkorn University, Patumwan, Bangkok 10330 (Thailand); Yokoi, Toshiyuki [Division of Catalytic Chemistry, Chemical Resources Laboratory, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503 (Japan); Ngamcharussrivichai, Chawalit, E-mail: Chawalit.Ng@chula.ac.th [Department of Chemical Technology, Faculty of Science, Chulalongkorn University, Patumwan, Bangkok 10330 (Thailand); Center of Excellence on Petrochemical and Materials Technology (PETROMAT), Chulalongkorn University, Patumwan, Bangkok 10330 (Thailand)

    2016-09-15

    In the present work, a series of lanthanum-doped mesostructured strontium titanate (LMST) materials with different La/Sr ratios were synthesized via a sol–gel combustion method in the presence of citric acid as a complexing agent and Pluronic P123 as a templating agent. The effects of the amount of doped La and calcination temperature on the physicochemical properties of the LMSTs were examined using various techniques. Powder X-ray diffraction confirmed the substitution of La{sup 3+} into the SrTiO{sub 3} lattice, generating cubic perovskite La{sub x}Sr{sub 1−x}TiO{sub 3}, for the LMST materials calcined at 600 °C. The purity and crystallinity of the desired perovskite phase were enhanced by citric acid addition. The solubility limit of La{sup 3+} substitution at an La/Sr ratio of 0.43 was determined by structural and morphological studies. Increasing the La doping amount decreased the crystallinity and compositional homogeneity, because an La-rich amorphous phase segregated on the surface, but improved the mesoporosity. N{sub 2} physisorption measurements indicated that the LMSTs had a bimodal pore size distribution, of which the larger one was characterized by the crystallite size of mixed oxides, and the specific surface area of 24.9–37.3 m{sup 2} g{sup −1}. The formation of mesopores in the LMST materials synthesized via sol–gel combustion was explained based on a combination of soft- and hard-templating chemistries. - Highlights: • La-doped mesoporous SrTiO{sub 3} (LMST) was prepared first time via sol-gel combustion. • Pluronic P123 triblock copolymer was used as a cheap templating agent. • Citric acid as a complexing agent enhanced the purity and crystallinity of SrTiO{sub 3}. • The textural properties of LMST were improved by increasing the La doping amount. • Mesopore formation was explained by a combined soft- and hard-templating route.

  13. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

    Science.gov (United States)

    Pasadhika, Sirichai; Rosenbaum, James T

    2014-01-01

    Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet’s disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine) may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet’s disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present work aims to provide a broad and updated review of the current and in-development systemic biologic agents for the treatment of noninfectious uveitis. PMID:24600203

  14. Resistance of an enamel-bonding agent to saliva and acid exposure in vitro assessed by liquid scintillation.

    Science.gov (United States)

    Schmidlin, P R; Göhring, T N; Sener, B; Lutz, F

    2002-06-01

    To determine the leakage and resistance of a bonding agent and a light-curing fine hybrid composite when exposed to saliva or lactic acid (pH 4) in vitro. Twenty discs in each of four groups of selected irradiated bovine lower central incisors were treated with one of three sealing options: an enamel bond (Heliobond, Vivadent, Schaan, Liechenstein) in a single-step application; Heliobond in a two-step application; and Tetric Flow (Vivadent) as the negative control. One group served as the positive control and remained unsealed. Loss of apatite was determined using the radiochemical method of liquid scintillation. The Cherenkov radiation was assessed in order to evaluate the acid resistance and leakage of smooth surface enamel bonding after exposure to saliva and lactic acid. In addition, replicas were made for SEM analysis of micromorphologic surface changes. A mean loss of 416.5 g (s.d. 57.0) apatite was observed over the unsealed sites following 14 days of exposure to lactic acid. The application of Heliobond in a one- and two-step application still revealed a remarkable degree of leakage, and substance losses of 196.5 g (s.d. 38.9) and 161.8 g (s.d. 39.7), but a protective potential was evident. In saliva, untreated, as well as sealed teeth, showed a modest leakage that was less than 20 g. When Tetric Flow was used (negative control) leakage was reduced to a minimum of 2.4 g (s.d. 1.0) in saliva and 12.8 g (s.d. 19.6) in lactic acid. These results were confirmed by SEM analysis. The method of liquid scintillation was revealed to be of considerable value in evaluating leakage and acid resistance of potential smooth enamel sealing options. Sealing with an unfilled resin still demonstrated remarkable levels of acid dissolution, although a protection tendency could be observed. This leads to the conclusion that there is a need for further investigation to establish more acid-resistant enamel sealing agents.

  15. PLASMA SPRAYED Al₂O₃-13 WT.%TiO₂ COATING SEALED WITH ORGANIC-INORGANIC HYBRID AGENT AND ITS CORROSION RESISTANCE IN ACID ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    Zehua Zhou

    2016-07-01

    Full Text Available A novel organic-inorganic hybrid material of γ-methacryloxypropyltrime-thoxysilane (KH570 -SiO₂ was fabricated by Sol-Gel method. The hybrid material was used as the sealing agent for the plasma sprayed Al₂O₃-13 wt.% TiO₂ coating. Infrared spectrum and grafted mechanism of the hybrid agent (HA were studied. Moreover, morphology and porosity, as well as characteristics of immersion plus electrochemical corrosion in acid environment of the coating with and without sealing treatment were evaluated, compared with those of the coating sealed with the conventional silicone resin agent (SRA. The results reveal that KH570 was successfully grafted onto the surface of SiO₂. The HA film sealed on the surface of the coating presents a little better quality than the SRA film. The porosities of the coatings after the sealing treatment decreased. Furthermore, the sealing treatment can improve efficiently the corrosion resistance of the coating in 5 vol.% HCl solution. The hybrid sealing agent can become a candidate for the plasma sprayed Al₂O₃-13 wt.% TiO₂ coating used in acid environment to overcome some disadvantages of organic agents such as severely environmental pollution.

  16. Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure.

    Science.gov (United States)

    Svensson, J Peter; Quirós Pesudo, Laia; McRee, Siobhan K; Adeleye, Yeyejide; Carmichael, Paul; Samson, Leona D

    2013-01-01

    Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS), N-Methyl-N-nitrosourea (MNU), N,N'-bis(2-chloroethyl)-N-nitroso-urea (BCNU), N-ethylnitrosourea (ENU)), two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN), benzene-1,4-diol (hydroquinone, HYQ)), and two non-genotoxic (methyl carbamate (MC) and dimethyl sulfoxide (DMSO)) compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.

  17. The influence of immunosuppressive drugs on neural stem/progenitor cell fate in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Skardelly, Marco, E-mail: Marco.Skardelly@med.uni-tuebingen.de [Department of Neurosurgery, University Hospital, Leipzig (Germany); Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany); Glien, Anja; Groba, Claudia; Schlichting, Nadine [Department of Neurosurgery, University Hospital, Leipzig (Germany); Kamprad, Manja [Institute of Clinical Immunology, Medical Faculty, University of Leipzig, Leipzig (Germany); Meixensberger, Juergen [Department of Neurosurgery, University Hospital, Leipzig (Germany); Milosevic, Javorina [Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig (Germany)

    2013-12-10

    In allogenic and xenogenic transplantation, adequate immunosuppression plays a major role in graft survival, especially over the long term. The effect of immunosuppressive drugs on neural stem/progenitor cell fate has not been sufficiently explored. The focus of this study is to systematically investigate the effects of the following four different immunotherapeutic strategies on human neural progenitor cell survival/death, proliferation, metabolic activity, differentiation and migration in vitro: (1) cyclosporine A (CsA), a calcineurin inhibitor; (2) everolimus (RAD001), an mTOR-inhibitor; (3) mycophenolic acid (MPA, mycophenolate), an inhibitor of inosine monophosphate dehydrogenase and (4) prednisolone, a steroid. At the minimum effective concentration (MEC), we found a prominent decrease in hNPCs' proliferative capacity (BrdU incorporation), especially for CsA and MPA, and an alteration of the NAD(P)H-dependent metabolic activity. Cell death rate, neurogenesis, gliogenesis and cell migration remained mostly unaffected under these conditions for all four immunosuppressants, except for apoptotic cell death, which was significantly increased by MPA treatment. - Highlights: • Four immunosuppresants (ISs) were tested in human neural progenitor cells in vitro. • Cyclosporine A and mycophenolic acid showed a prominent anti-proliferative activity • Mycophenolic acid exhibited a significant pro-apoptotic effect. • NAD(P)H-dependent metabolic activity was occasionally induced by ISs. • Neuronal differentiation and migration potential remained unaffected by ISs treatment.

  18. Composition dependence of the synergistic effect of nucleating agent and plasticizer in poly(lactic acid: A Mixture Design study

    Directory of Open Access Journals (Sweden)

    M. K. Fehri

    2016-04-01

    Full Text Available Blends consisting of commercial poly(lactic acid (PLA, poly(lactic acid oligomer (OLA8 as plasticizer and a sulfonic salt of a phthalic ester and poly(D-lactic acid as nucleating agents were prepared by melt extrusion, following a Mixture Design approach, in order to systematically study mechanical and thermal properties as a function of composition. The full investigation was carried out by differential scanning calorimetry (DSC, dynamic mechanical thermal analysis (DMTA and tensile tests. The crystallization half-time was also studied at 105 °C as a function of the blends composition. A range of compositions in which the plasticizer and the nucleation agent minimized the crystallization half-time in a synergistic way was clearly identified thanks to the application of the Mixture Design approach. The results allowed also the identification of a composition range to maximize the crystallinity developed during the rapid cooling below glass transition temperature in injection moulding, thus allowing an easier processing of PLA based materials. Moreover the mechanical properties were discussed by correlating them to the chemical structural features and thermal behaviour of blends.

  19. A new approach in the preparation of dendrimer-based bifunctional diethylenetriaminepentaacetic acid MR contrast agent derivatives.

    Science.gov (United States)

    Nwe, Kido; Xu, Heng; Regino, Celeste Aida S; Bernardo, Marcelino; Ileva, Lilia; Riffle, Lisa; Wong, Karen J; Brechbiel, Martin W

    2009-07-01

    In this paper, we report a new method to prepare and characterize a contrast agent based on a fourth-generation (G4) polyamidoamine (PAMAM) dendrimer conjugated to the gadolinium complex of the bifunctional diethylenetriamine pentaacetic acid derivative (1B4M-DTPA). The method involves preforming the metal-ligand chelate in alcohol prior to conjugation to the dendrimer. The dendrimer-based agent was purified by a Sephadex G-25 column and characterized by elemental analysis. The analysis and SE-HPLC data gave a chelate to dendrimer ratio of 30:1 suggesting conjugation at approximately every other amine terminal on the dendrimer. Molar relaxivity of the agent measured at pH 7.4 displayed a higher value than that of the analogous G4 dendrimer based agent prepared by the postmetal incorporation method (r(1) = 26.9 vs 13.9 mM(-1) s(-1) at 3 T and 22 degrees C). This is hypothesized to be due to the higher hydrophobicity of this conjugate and the lack of available charged carboxylate groups from noncomplexed free ligands that might coordinate to the metal and thus also reduce water exchange sites. Additionally, the distribution populations of compounds that result from the postmetal incorporation route are eliminated from the current product simplifying characterization as quality control issues pertaining to the production of such agents for clinical use as MR contrast agents. In vivo imaging in mice showed a reasonably fast clearance (t(1/2) = 24 min) suggesting a viable agent for use in clinical application.

  20. A possible simplification for the estimation of area under the curve (AUC₀₋₁₂) of enteric-coated mycophenolate sodium in renal transplant patients receiving tacrolimus.

    Science.gov (United States)

    Fleming, Denise H; Mathew, Binu S; Prasanna, Samuel; Annapandian, Vellaichamy M; John, George T

    2011-04-01

    Enteric-coated mycophenolate sodium (EC-MPS) is widely used in renal transplantation. With a delayed absorption profile, it has not been possible to develop limited sampling strategies to estimate area under the curve (mycophenolic acid [MPA] AUC₀₋₁₂), which have limited time points and are completed in 2 hours. We developed and validated simplified strategies to estimate MPA AUC₀₋₁₂ in an Indian renal transplant population prescribed EC-MPS together with prednisolone and tacrolimus. Intensive pharmacokinetic sampling (17 samples each) was performed in 18 patients to measure MPA AUC₀₋₁₂. The profiles at 1 month were used to develop the simplified strategies and those at 5.5 months used for validation. We followed two approaches. In one, the AUC was calculated using the trapezoidal rule with fewer time points followed by an extrapolation. In the second approach, by stepwise multiple regression analysis, models with different time points were identified and linear regression analysis performed. Using the trapezoidal rule, two equations were developed with six time points and sampling to 6 or 8 hours (8hrAUC[₀₋₁₂exp]) after the EC-MPS dose. On validation, the 8hrAUC(₀₋₁₂exp) compared with total measured AUC₀₋₁₂ had a coefficient of correlation (r²) of 0.872 with a bias and precision (95% confidence interval) of 0.54% (-6.07-7.15) and 9.73% (5.37-14.09), respectively. Second, limited sampling strategies were developed with four, five, six, seven, and eight time points and completion within 2 hours, 4 hours, 6 hours, and 8 hours after the EC-MPS dose. On validation, six, seven, and eight time point equations, all with sampling to 8 hours, had an acceptable r with the total measured MPA AUC₀₋₁₂ (0.817-0.927). In the six, seven, and eight time points, the bias (95% confidence interval) was 3.00% (-4.59 to 10.59), 0.29% (-5.4 to 5.97), and -0.72% (-5.34 to 3.89) and the precision (95% confidence interval) was 10

  1. Uranium accumulation in Brassica rapa L. and effect of citric acid and humic acids as chelating agents; Acumulacion de uranio en Brassica rapa L. y efecto del acido citrico y acidos humicos como agentes quelantes

    Energy Technology Data Exchange (ETDEWEB)

    Lopez del R, H.; Perez C, G. A.; Davila R, J. I.; Mireles G, F. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98060 Zacatecas, Zac. (Mexico); Rodriguez H, G., E-mail: hlopezdelrio@hotmail.com [Universidad Autonoma de Zacatecas, Unidad Academica de Agronomia, Carretera Zacatecas-Guadalajara Km 15.5, Cieneguillas, Zacatecas (Mexico)

    2016-09-15

    Phyto extraction is a technique that makes use of plants for the remediation of soils contaminated with heavy metals. In this study the uranium incorporation in the Brassica rapa L. species was evaluated, in artificially contaminated inert soils with 40 mg U/kg, and the effect of adding of the natural chelating agents citric acid and humic acids in the accumulation of uranium was analyzed. Soil free of organic matter and biologically inert was obtained by controlled calcination s of natural soil. Cultures in the prepared soil consisted of five growth treatments: 1) cultivation without uranium or additives; 2) cultivation in the uranium presence; 3) cultivation with uranium and citric acid (2 g/kg); 4) cultivation with uranium and humic acids (10 g/kg); 5) uranium cultivation and combination of citric and humic acids at the same concentrations. There was no adverse effect on plant growth with the presence of uranium at the given concentration. Regarding the controls, the total biomass in the presence of uranium was slightly higher, while the addition of humic acids significantly stimulated the production of biomass with respect to the citric acid. The combined action of organic acids produced the highest amount of biomass. The efficiency of phyto extraction followed the order Humic acids (301 μg U/g) > Non-assisted (224 μg U/g) >> Citric acid + Humic acids (68 μg U/g) > Citric acid (59 μg U/g). The values of uranium concentration in the total biomass show that the species Brassica rapa L. has the capacity of phyto extraction of uranium in contaminated soils. The addition of humic acids increases the uranium extraction while the addition of citric acid disadvantages it. (Author)

  2. Removal of heavy metals from polluted soil using the citric acid fermentation broth: a promising washing agent.

    Science.gov (United States)

    Zhang, Hongjiao; Gao, Yuntao; Xiong, Huabin

    2017-04-01

    The citric acid fermentation broth was prepared and it was employed to washing remediation of heavy metal-polluted soil. A well-defined washing effect was obtained, the removal percentages using citric acid fermentation broth are that 48.2% for Pb, 30.6% for Cu, 43.7% for Cr, and 58.4% for Cd and higher than that using citric acid solution. The kinetics of heavy metals desorption can be described by the double constant equation and Elovich equation and is a heterogeneous diffusion process. The speciation analysis shows that the citric acid fermentation broth can effectively reduce bioavailability and environmental risk of heavy metals. Spectroscopy characteristics analysis suggests that the washing method has only a small effect on the mineral composition and does not destroy the framework of soil system. Therefore, the citric acid fermentation broth is a promising washing agent and possesses a potential practical application value in the field of remediation of soils with a good washing performance.

  3. Application and appreciation of chemical sand fixing agent-poly (aspartic acid) and its composites

    Energy Technology Data Exchange (ETDEWEB)

    Yang Jun; Cao Hui; Wang Fang [Beijing Key Laboratory of Bioprocess, Beijing University of Chemical Technology, Beijing 100029 (China); Tan Tianwei [Beijing Key Laboratory of Bioprocess, Beijing University of Chemical Technology, Beijing 100029 (China)], E-mail: twtan@mail.buct.edu.cn

    2007-12-15

    The sand fixing agent-poly (aspartic acid) (PASP) and its composites were applied in the field by two forms (spraying around by PASP solution and PASP powder directly). It was found that the sand fixing effect in powder form was not as good as in solution form, but it was more practical in dry region. It needed 9, 6 and 7 days for PASP, xanthan gum-PASP (X2) and ethyl cellulose-PASP (E3) to attain the maximal mechanical strength after they were applied, respectively. The sand fixing effect decreased when the material was subjected to repeated hydration-dehydration cycles and the material had no negative influence on plant growth. The PASP and its composites had water-retaining ability and could reduce the water evaporation. - The sand fixing agent was applied in powder form and it had no negative influence on plant growth.

  4. Treatment Algorithms in Systemic Lupus Erythematosus.

    Science.gov (United States)

    Muangchan, Chayawee; van Vollenhoven, Ronald F; Bernatsky, Sasha R; Smith, C Douglas; Hudson, Marie; Inanç, Murat; Rothfield, Naomi F; Nash, Peter T; Furie, Richard A; Senécal, Jean-Luc; Chandran, Vinod; Burgos-Vargas, Ruben; Ramsey-Goldman, Rosalind; Pope, Janet E

    2015-09-01

    To establish agreement on systemic lupus erythematosus (SLE) treatment. SLE experts (n = 69) were e-mailed scenarios and indicated preferred treatments. Algorithms were constructed and agreement determined (≥50% respondents indicating ≥70% agreement). Initially, 54% (n = 37) responded suggesting treatment for scenarios; 13 experts rated agreement with scenarios. Fourteen of 16 scenarios had agreement as follows: discoid lupus: first-line therapy was topical agents and hydroxychloroquine and/or glucocorticoids then azathioprine and subsequently mycophenolate (mofetil); uncomplicated cutaneous vasculitis: initial treatment was glucocorticoids ± hydroxychloroquine ± methotrexate, followed by azathioprine or mycophenolate and then cyclophosphamide; arthritis: initial therapy was hydroxychloroquine and/or glucocorticoids, then methotrexate and subsequently rituximab; pericarditis: first-line therapy was nonsteroidal antiinflammatory drugs, then glucocorticoids with/without hydroxychloroquine, then azathioprine, mycophenolate, or methotrexate and finally belimumab or rituximab, and/or a pericardial window; interstitial lung disease/alveolitis: induction was glucocorticoids and mycophenolate or cyclophosphamide, then rituximab or intravenous gamma globulin (IVIG), and maintenance followed with azathioprine or mycophenolate; pulmonary hypertension: glucocorticoids and mycophenolate or cyclophosphamide and an endothelin receptor antagonist were initial therapies, subsequent treatments were phosphodiesterase-5 inhibitors and then prostanoids and rituximab; antiphospholipid antibody syndrome: standard anticoagulation with/without hydroxychloroquine, then a thrombin inhibitor for venous thrombosis, versus adding aspirin or platelet inhibition drugs for arterial events; mononeuritis multiplex and central nervous system vasculitis: first-line therapy was glucocorticoids and cyclophosphamide followed by maintenance with azathioprine or mycophenolate, and

  5. Stabilized radiographic scanning agents

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1982-01-01

    Stable compositions useful as technetium 99m-based scintigraphic agents comprise gentisic acid or a pharmaceutically-acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in pertechnetate-99m (sup(99m)TcOsub(4)sup(-)) solution. The compositions are especially useful in combination with a phosphate or phosphonate material that carries the radionuclide to bone, thus providing a skeletal imaging agent

  6. Reductive Leaching Kinetics of Low Grade Manganese Deposits in H2SO4 Solution Using Malonic Acid as Reducing Agent

    OpenAIRE

    Taysser Lasheen; S. A. Abu Elenein; W. A. Saleh; A. H Orabi; D. A Ismaiel

    2014-01-01

    A leaching process was developed to extract manganese and metal values from Alloga manganese concentrate. The preferential leaching process was achieved through reductive leaching in dilute sulfuric acid medium with malonic acid as the reducing agent. Leaching parameters were optimized as 1.0 M H2SO4, 10% malonic acid in solid/liquid ratio 1:10 for 90 min at 80 C and using ore ground to – 74 µm. Under these conditions, the leaching efficiency of manganese reaches 97%, whilst iron dissolution ...

  7. Chemical Agents

    Science.gov (United States)

    ... CR) see Riot Control Agents Digitalis Distilled mustard (HD) see Sulfur mustard E Ethylene glycol F Fentanyls and other opioids H Hydrazine Hydrofluoric acid (hydrogen fluoride) Hydrogen chloride Hydrogen cyanide (AC) Hydrogen ...

  8. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    Directory of Open Access Journals (Sweden)

    Hou L

    2015-07-01

    Full Text Available Lin Hou,* Huijuan Zhang,* Yating Wang, Lili Wang, Xiaomin Yang, Zhenzhong ZhangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China*These authors contributed equally to this workAbstract: A tumor-targeting carrier, hyaluronic acid (HA-functionalized single-walled carbon nanotubes (SWCNTs, was explored to deliver magnetic resonance imaging (MRI contrast agents (CAs targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor.Keywords: gadolinium, magnetic resonance, SWCNTs, hyaluronic acid, contrast agent

  9. Determination of methyl-, 2-hydroxyethyl- and 2-cyanoethylmercapturic acids as biomarkers of exposure to alkylating agents in cigarette smoke.

    Science.gov (United States)

    Scherer, Gerhard; Urban, Michael; Hagedorn, Heinz-Werner; Serafin, Richard; Feng, Shixia; Kapur, Sunil; Muhammad, Raheema; Jin, Yan; Sarkar, Mohamadi; Roethig, Hans-Juergen

    2010-10-01

    Alkylating agents occur in the environment and are formed endogenously. Tobacco smoke contains a variety of alkylating agents or precursors including, among others, N-nitrosodimethylamine (NDMA), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), acrylonitrile and ethylene oxide. We developed and validated a method for the simultaneous determination of methylmercapturic acid (MMA, biomarker for methylating agents such as NDMA and NNK), 2-hydroxyethylmercapturic acid (HEMA, biomarker for ethylene oxide) and 2-cyanoethylmercapturic acid (CEMA, biomarker for acrylonitrile) in human urine using deuterated internal standards of each compound. The method involves liquid/liquid extraction of the urine sample, solid phase extraction on anion exchange cartridges, derivatization with pentafluorobenzyl bromide (PFBBr), liquid/liquid extraction of the reaction mixture and LC-MS/MS analysis with positive electrospray ionization. The method was linear in the ranges of 5.00-600, 1.00-50.0 and 1.50-900 ng/ml for MMA, HEMA and CEMA, respectively. The method was applied to two clinical studies in adult smokers of conventional cigarettes who either continued smoking conventional cigarettes, were switched to test cigarettes consisting of either an electrically heated cigarette smoking system (EHCSS) or having a highly activated carbon granule filter that were shown to have reduced exposure to specific smoke constituents, or stopped smoking. Urinary excretion of MMA was found to be unaffected by switching to the test cigarettes or stop smoking. Urinary HEMA excretion decreased by 46 to 54% after switching to test cigarettes and by approximately 74% when stopping smoking. Urinary CEMA excretion decreased by 74-77% when switching to test cigarettes and by approximately 90% when stopping smoking. This validated method for urinary alkylmercapturic acids is suitable to distinguish differences in exposure not only between smokers and nonsmokers but also between smoking of conventional and

  10. Genomic phenotyping by barcode sequencing broadly distinguishes between alkylating agents, oxidizing agents, and non-genotoxic agents, and reveals a role for aromatic amino acids in cellular recovery after quinone exposure.

    Directory of Open Access Journals (Sweden)

    J Peter Svensson

    Full Text Available Toxicity screening of compounds provides a means to identify compounds harmful for human health and the environment. Here, we further develop the technique of genomic phenotyping to improve throughput while maintaining specificity. We exposed cells to eight different compounds that rely on different modes of action: four genotoxic alkylating (methyl methanesulfonate (MMS, N-Methyl-N-nitrosourea (MNU, N,N'-bis(2-chloroethyl-N-nitroso-urea (BCNU, N-ethylnitrosourea (ENU, two oxidizing (2-methylnaphthalene-1,4-dione (menadione, MEN, benzene-1,4-diol (hydroquinone, HYQ, and two non-genotoxic (methyl carbamate (MC and dimethyl sulfoxide (DMSO compounds. A library of S. cerevisiae 4,852 deletion strains, each identifiable by a unique genetic 'barcode', were grown in competition; at different time points the ratio between the strains was assessed by quantitative high throughput 'barcode' sequencing. The method was validated by comparison to previous genomic phenotyping studies and 90% of the strains identified as MMS-sensitive here were also identified as MMS-sensitive in a much lower throughput solid agar screen. The data provide profiles of proteins and pathways needed for recovery after both genotoxic and non-genotoxic compounds. In addition, a novel role for aromatic amino acids in the recovery after treatment with oxidizing agents was suggested. The role of aromatic acids was further validated; the quinone subgroup of oxidizing agents were extremely toxic in cells where tryptophan biosynthesis was compromised.

  11. Update on the use of systemic biologic agents in the treatment of noninfectious uveitis

    Directory of Open Access Journals (Sweden)

    Pasadhika S

    2014-02-01

    Full Text Available Sirichai Pasadhika,1 James T Rosenbaum2 1Department of Ophthalmology, Southern Arizona Veterans Administration Health Care System, Tucson, AZ, USA; 2Legacy Devers Eye Institute, Portland, OR, USA Abstract: Uveitis is one of the leading causes of blindness worldwide. Noninfectious uveitis may be associated with other systemic conditions, such as human leukocyte antigen B27-related spondyloarthropathies, inflammatory bowel disease, juvenile idiopathic arthritis, Behçet's disease, and sarcoidosis. Conventional therapy with corticosteroids and immunosuppressive agents (such as methotrexate, azathioprine, mycophenolate mofetil, and cyclosporine may not be sufficient to control ocular inflammation or prevent non-ophthalmic complications in refractory patients. Off-label use of biologic response modifiers has been studied as primary and secondary therapeutic agents. They are very useful when conventional immunosuppressive therapy has failed or has been poorly tolerated, or to treat concomitant ophthalmic and systemic inflammation that might benefit from these medications. Biologic therapy, primarily infliximab, and adalimumab, have been shown to be rapidly effective for the treatment of various subtypes of refractory uveitis and retinal vasculitis, especially Behçet's disease-related eye conditions and the uveitis associated with juvenile idiopathic arthritis. Other agents such as golimumab, abatacept, canakinumab, gevokizumab, tocilizumab, and alemtuzumab may have great future promise for the treatment of uveitis. It has been shown that with proper monitoring, biologic therapy can significantly improve quality of life in patients with uveitis, particularly those with concurrent systemic symptoms. However, given high cost as well as the limited long-term safety data, we do not routinely recommend biologics as first-line therapy for noninfectious uveitis in most patients. These agents should be used with caution by experienced clinicians. The present

  12. Erbium trifluoromethanesulfonate-catalyzed Friedel–Crafts acylation using aromatic carboxylic acids as acylating agents under monomode-microwave irradiation

    DEFF Research Database (Denmark)

    Tran, Phuong Hoang; Hansen, Poul Erik; Nguyen, Hai Truong

    2015-01-01

    Erbium trifluoromethanesulfonate is found to be a good catalyst for the Friedel–Crafts acylation of arenes containing electron-donating substituents using aromatic carboxylic acids as the acylating agents under microwave irradiation. An effective, rapid and waste-free method allows the preparation...... of a wide range of aryl ketones in good yields and in short reaction times with minimum amounts of waste...

  13. Acid-base properties of 2-phenethyldithiocarbamoylacetic acid, an antitumor agent

    Science.gov (United States)

    Novozhilova, N. E.; Kutina, N. N.; Petukhova, O. A.; Kharitonov, Yu. Ya.

    2013-07-01

    The acid-base properties of the 2-phenethyldithiocarbamoylacetic acid (PET) substance belonging to the class of isothiocyanates and capable of inhibiting the development of tumors on many experimental models were studied. The acidity and hydrolysis constants of the PET substance in ethanol, acetone, aqueous ethanol, and aqueous acetone solutions were determined from the data of potentiometric (pH-metric) titration of ethanol and acetone solutions of PET with aqueous solidum hydroxide at room temperature.

  14. Stable radiographic scanning agents

    International Nuclear Information System (INIS)

    1976-01-01

    Stable compositions which are useful in the preparation of Technetium-99m-based scintigraphic agents are discussed. They are comprised of ascorbic acid or a pharmaceutically acceptable salt or ester thereof in combination with a pertechnetate reducing agent or dissolved in oxidized pertechnetate-99m (sup(99m)TcO 4 - ) solution

  15. Aquaculture in Cameroon and potential of lactic acid bacteria to be used as diseases controlling agents. A Review

    Directory of Open Access Journals (Sweden)

    Kaktchan, Pierre Marie

    2015-08-01

    Full Text Available Aquaculture is the world’s fastest growing food production sector and can be a great solution to the massive demand for protein of animal due to increase in the Cameroonian population. This review summarizes the past and present status of fish aquaculture in Cameroon, the new challenges for intensifying fish production and evaluates the possibility of using lactic acid bacteria as disease control agents in order to overcome these challenges. Fish farming started in Cameroon in the late 1940s, and has seen little progress since the last ten years, but the production is still insufficient to meet the demand of the population estimated at 400 000 tons in 2015. In order to reduce massive fish imports, Cameroon plans to produce 100 000 tons of fish by commercial aquaculture. Achieving this task needs quality and quantity of fingerlings, and probiotic lactic acid bacteria instead of antibiotics could be used as disease control agents in young fish hatching and ponds in order to boost and ensure quality and quantity production.

  16. Use of chelating agents as immovable phase in extraction chromatography

    International Nuclear Information System (INIS)

    Sebesta, F.

    1978-01-01

    Extraction chromatography using chelating agents is reviewed. The theory of element extraction by chelating agents and factors influencing this process (pH, extracting agent concentration in organic phase, masking agent concentration in aqueous phase) are briefly considered. The effect of kinetic factors on the extraction chromatography process is discussed. Ways of preparing columns are emphasized. Examples of using chelating reagents in various extraction chromatography systems are given. β-Diketones, oximes, hydroxamic acids, dithizon, diethyl dithiocarbamic acid are chosen as chelating agents

  17. From boron analogues of amino acids to boronated DNA: potential new pharmaceuticals and neutron capture agents

    International Nuclear Information System (INIS)

    Spielvogel, B.F.; Sood, Anup; Duke Univ., Durham, NC; Shaw, B.R.; Hall, I.H.

    1991-01-01

    Isoelectronic and isostructural boron analogues of the α-amino acids ranging from simple glycine analogues such as H 3 NBH 2 COOH and Me 2 NHBH 2 COOH to alanine analogues have been synthesised. A diverse variety of analogues, including precursors and derivatives (such as peptides) have potent pharmacological activity, including anticancer, antiinflammatory, analgesic, and hypolipidemic activity in animal model studies and in vitro cell cultures. Boronated nucleosides and (oligo)nucleotides, synthetic oligonucleotide analogues of ''antisense'' agents interact with a complementary nucleic acid sequence blocking the biological effect of the target sequence. Nucleosides boronated on the pyrimidine and purine bases have been prepared. It has been established that an entirely new class of nucleic acid derivatives is feasible in which one of the non-bridging oxygens in the internucleotide phosphodiester linkage can be replaced by an isoelectronic analogue, the borane group, (BH 3 ). The boronated oligonucleotides can be viewed as hybrids of the normal oxygen oligonucleotides and the methylphosphonate oligonucleotides. (author)

  18. Determination of trace elements by neutron activation analysis using dinonylnaphtalene sulfonic acid as a preconcentrating agent

    International Nuclear Information System (INIS)

    Yang, M.H.; Chen, P.Y.; Tseng, C.L.; Yeh, S.J.; Weng, P.S.

    1977-01-01

    Dinonylnaphthalene sulfonic acid (HD) has been used as a preconcentrating agent to enrich trace metal ions and to separate the interfering elements such as Na, K, Cl and Br, which normally exist in the natural aqueous systems. Experiments were performed by extracting the ions in the aqueous medium with HD in n-hexane and subsequently backextracted into a minimal volume of acid solution. Factors influencing the extraction efficiency of the ions of interest were investigated. The preconcentration technique has been successfully applied to the determination by neutron activation analysis of trace elements in natural water and biological materials. Both short-lived nuclides (Mg, Al, Ca, Mn) and long-lived nuclides (Sm, Eu, Zn, La, Cr, Sc, Fe, Co) in the ppb-level concentrations were determined. (T.G.)

  19. Regeneration of Three-Way Automobile Catalysts using Biodegradable Metal Chelating Agent – S, S-Ethylenediamine Disuccinic Acid (S, S-EDDS)

    Science.gov (United States)

    Regeneration of the activity of three-way catalytic converters (TWCs) was tested for the first time using a biodegradable metal chelating agent (S, S. Ethylenediamine disuccinic acid (S, S-EDDS). The efficiency of this novel environmentally friendly solvent in removing various c...

  20. Perspective on future therapy of vasculitis.

    Science.gov (United States)

    Boumpas, D T; Kritikos, H D; Daskalakis, N G

    2000-10-01

    This article summarizes recent advances in the management of various vasculitic syndromes and discusses potential new therapies based on a better understanding of their pathogenesis and natural history. Current efforts for optimization of testing for antineutrophil cytoplasmic antibodies and improvement of diagnostic criteria will certainly have a significant impact on future therapy. Biologic agents such as interferon-alpha are already in use in various vasculitides, whereas others, such as inhibitors of tumor necrosis factor-alpha, are in phase I clinical trials. Agents that selectively inhibit distinct steps in the pathogenesis of vasculitis are in preclinical or early clinical stages of development. Newer (mycophenolate mofetil, leflunamide) or older (methotrexate, azathioprine) immunosuppresive agents are finding new roles in the management of vasculitides. For patients with severe vasculitis, short-term use of cytotoxic agents, such as cyclophosphamide, alone or in combination with biologic agents, may expedite remission, which could then be better maintained with other, less toxic (and less expensive) immunosuppressive agents, such as methotrexate, azathioprine, mycophenolate mofetil, and leflunamide. For patients with mild or moderately severe vasculitis, these latter agents alone may be adequate. New therapeutic studies in vasculitis should better address the impact of therapy on health-related quality of life and its long-term toxicity.

  1. The Usability of Boric Acid as an Alternative Foaming Agent on the Fabrication of Al/Al2O3 Composite Foams

    Science.gov (United States)

    Yaman, Bilge; Onuklu, Eren; Korpe, Nese O.

    2017-09-01

    Pure Al and alumina (2, 5, 10 wt.% Al2O3)-added Al composite foams were fabricated through powder metallurgy technique, where boric acid (H3BO3) is employed as a new alternative foaming agent. It is aimed to determine the effects of boric acid on the foaming behavior and cellular structure and also purposed to develop the mechanical properties of Al foams by addition of Al2O3. Al and Al composite foams with porosity fraction in the range of 46-53% were achieved by sintering at 620 °C for 2 h. Cell morphology was characterized using a combination of stereomicroscope equipped with image analyzer and scanning electron microscopy. Microhardness values were measured via using Vickers indentation technique. Quasi-static compression tests were performed at strain rate of 10-3 s-1. Compressive strength and energy absorption of the composite foams enhanced not only by the increasing weight fraction of alumina, but also by the usage of boric acid which leads to formation of boron oxide (B2O3) acting as a binder in obtaining dense cell walls. The results revealed that the boric acid has outstanding potential as foaming agent in the fabrication of Al and Al composite foams by providing improved mechanical properties.

  2. Adrenal imaging agents

    International Nuclear Information System (INIS)

    Davis, M.A.; Hanson, R.N.; Holman, B.L.

    1980-01-01

    The goals of this proposal are the development of selenium-containing analogs of the aromatic amino acids as imaging agents for the pancreas and of the adrenal cortex enzyme inhibitors as imaging agents for adrenal pathology. The objects for this year include (a) the synthesis of methylseleno derivatives of phenylalanine and tryptophan, and (b) the preparation and evaluation of radiolabeled iodobenzoyl derivatives of the selenazole and thiazole analogs of metyrapone and SU-9055

  3. Agentes imunossupressores, talidomida e ácido valpróico nas síndromes mielodisplásicas Immunosuppressive agents, thalidomide and valproate acid in myelodysplastic syndromes

    Directory of Open Access Journals (Sweden)

    Elvira R. P. Velloso

    2006-09-01

    Full Text Available Agentes imunossupressores, como a globulina antitimocítica (GAL ou antilinfocítica (GAL e a ciclosporina A têm mostrado eficácia nas SMD, particularmente nos subtipos Anemias refratária (AR e nas SMD com fenótipo HLA-DR15, independente do grau de celularidade medular. Outras drogas disponíveis em nosso meio, de baixo custo, como a talidomida podem ser utilizada em pacientes refratários, e o ácido valpróico está sendo utilizado em ensaios clínicos. A quantificação da resposta a drogas deve utilizar os critérios de resposta do International Working Group (IWG. É proposto um fluxograma para uso de fatores de crescimento, agentes imunossupressores e talidomida em pacientes com SMD, de baixo risco, não candidatos a transplante de medula óssea (TMO.Patients with refractory anemia subtypes and HLA-DR15 with any degree of marrow cellularity have good responses to immunosuppressive agents, such as antithymocyte globulin, antilymphocyte globulin and cyclosporine A. Other cheaper drugs available in Brazil, including thalidomide may be useful in refractory patients. Valproate acid has started to be used in clinical trials. Response to treatment should be reported using the criteria proposed by the International Working Group. The use of growth factors, immunosuppressive agents and thalidomide in low risk patients with myelodysplastic syndromes who are not candidates for hematopoietic stem cell transplantation is suggested at the end of this publication.

  4. Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

    Science.gov (United States)

    Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

    2017-02-01

    Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Aminocaproic Acid and Tranexamic Acid Fail to Reverse Dabigatran-Induced Coagulopathy.

    Science.gov (United States)

    Levine, Michael; Huang, Margaret; Henderson, Sean O; Carmelli, Guy; Thomas, Stephen H

    In recent years, dabigatran has emerged as a popular alternative to warfarin for treatment of atrial fibrillation. If rapid reversal is required, however, no reversal agent has clearly been established. The primary purpose of this manuscript was to evaluate the efficacy of tranexamic acid and aminocaproic acid as agents to reverse dabigatran-induced coagulopathy. Rats were randomly assigned to 6 groups. Each rat received either dabigatran or oral placebo, followed by saline, tranexamic acid, or aminocaproic acid. An activated clotting test was used to measure the coagulopathy. Neither tranexamic acid nor aminocaproic acid successfully reversed dabigatran-induced coagulopathy. In this rodent model of dabigatran-induced coagulopathy, neither tranexamic acid nor aminocaproic acid were able to reverse the coagulopathy.

  6. Indole-3-acetic acid biosynthesis in Fusarium delphinoides strain GPK, a causal agent of Wilt in Chickpea.

    Science.gov (United States)

    Kulkarni, Guruprasad B; Sanjeevkumar, S; Kirankumar, B; Santoshkumar, M; Karegoudar, T B

    2013-02-01

    Fusarium delphinoides (Ascomycota; Nectriaceae) is an indole-3-acetic acid (IAA) producing plant pathogen and a causal agent of wilt in chickpea. The IAA biosynthetic pathway in F. delphinoides strain GPK (FDG) was examined by analyzing metabolic intermediates and by feeding experiments. Gas chromatograph (GC) analysis of FDG culture filtrates showed the presence of metabolic intermediates of indole-3-pyruvic acid (IPyA), indole-3-acetamide (IAM), and tryptamine (TRA) pathways. The different IAA biosynthetic pathways were further confirmed by identifying the presence of different enzymes of these pathways. Substrate specificity study of aromatic amino acid aminotransferase revealed that the enzyme is highly specific for tryptophan (Trp) and α-ketoglutarate (α-kg) as amino group donor and acceptor, respectively. Furthermore, the concentration-dependent effect of exogenous IAA on fungal growth was established. Low concentration of exogenous IAA increases the fungal growth and at high concentration it decreases the growth of FDG.

  7. Mycophenolate pharmacokinetics and pharmacodynamics in belatacept treated renal allograft recipients – a pilot study

    Directory of Open Access Journals (Sweden)

    Stenstrøm Jean

    2009-07-01

    Full Text Available Abstract Background Mycophenolic acid (MPA is widely used as part of immunosuppressive regimens following allograft transplantation. The large pharmacokinetic (PK and pharmacodynamic (PD variability and narrow therapeutic range of MPA provide a potential for therapeutic drug monitoring. The objective of this pilot study was to investigate the MPA PK and PD relation in combination with belatacept (2nd generation CTLA4-Ig or cyclosporine (CsA. Methods Seven renal allograft recipients were randomized to either belatacept (n = 4 or cyclosporine (n = 3 based immunosuppression. Samples for MPA PK and PD evaluations were collected predose and at 1, 2 and 13 weeks posttransplant. Plasma concentrations of MPA were determined by HPLC-UV. Activity of inosine monophosphate dehydrogenase (IMPDH and the expressions of two IMPDH isoforms were measured in CD4+ cells by HPLC-UV and real-time reverse-transcription PCR, respectively. Subsets of T cells were characterized by flow cytometry. Results The MPA exposure tended to be higher among belatacept patients than in CsA patients at week 1 (P = 0.057. Further, MPA concentrations (AUC0–9 h and C0 increased with time in both groups and were higher at week 13 than at week 2 (P = 0.031, n = 6. In contrast to the postdose reductions of IMPDH activity observed early posttransplant, IMPDH activity within both treatment groups was elevated throughout the dosing interval at week 13. Transient postdose increments were also observed for IMPDH1 expression, starting at week 1. Higher MPA exposure was associated with larger elevations of IMPDH1 (r = 0.81, P = 0.023, n = 7 for MPA and IMPDH1 AUC0–9 h at week 1. The maximum IMPDH1 expression was 52 (13–177% higher at week 13 compared to week 1 (P = 0.031, n = 6. One patient showed lower MPA exposure with time and did neither display elevations of IMPDH activity nor IMPDH1 expression. No difference was observed in T cell subsets between treatment groups. Conclusion The

  8. Chelating agents as stationary phase in extraction chromatography, ch. 11

    International Nuclear Information System (INIS)

    Sebesta, F.

    1975-01-01

    Chelating agents have been used largely in extraction chromatography for separations related to activation analysis, for concentration of metals from dilute solutions, and for preparation of radiochemically pure or carrier-free radionuclides. This review deals with the theory of extraction by chelating agents, the experimental technique, and the chelating agents and systems used (β-diketones, oximes, hydroxamic acid, dithizone and diethyldithiocarbamic acid)

  9. Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments.

    Science.gov (United States)

    Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

    2013-10-24

    Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression as well as resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent for imaging the acidic tumor microenvironment. The preparation included the conjugation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water-soluble glycol chitosan (GC) polymer, which contains pH-titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate-to-polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM(-1) s(-1). GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor-bearing mice 2 h postinjection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment.

  10. 器官移植患者的霉酚酸酯治疗药物监测%Therapeutic drug monitoring of mycophenolate mofetil in patients undergoing organ transplantation

    Institute of Scientific and Technical Information of China (English)

    崔学艳; 施孝金

    2009-01-01

    麦考酚酸酯(霉酚酸酯,mycophenlate mofetil,MMF)是麦考酚酸(霉酚酸,mycophenolic acid,MPA)的一种酯类衍生物。MMF无生物活性,口服后迅速水解为具活性的MPA。MMF是近年来发现的一种新型免疫抑制剂,临床上主要用于预防和治疗器官移植排斥反应。

  11. Induction of immunological tolerance in the pig-to-baboon xenotransplantation model : studies aimed at achieving mixed hematopoietic chimerism and preventing associated thrombotic complications

    NARCIS (Netherlands)

    I.P.J. Alwayn (Ian)

    2001-01-01

    textabstractThe outcome of clinical organ transplantation has dramatically improved since the introduction of cyclosporine (CyA) in 1979 and of other, more recently introduced, immunosuppressive agents such as azathioprine, mycophenolate mofetil, tacrolimus and sirolimus. Furthermore, due to more

  12. Successful treatment of pediatric IgG4 related systemic disease with mycophenolate mofetil: case report and a review of the pediatric autoimmune pancreatitis literature

    Directory of Open Access Journals (Sweden)

    Cron Randy Q

    2011-01-01

    Full Text Available Abstract Autoimmune pancreatitis is frequently associated with elevated serum and tissue IgG4 levels in the adult population, but there are few reports of pediatric autoimmune pancreatitis, and even fewer reports of IgG4 related systemic disease in a pediatric population. The standard of care treatment in adults is systemic corticosteroids with resolution of symptoms in most cases; however, multiple courses of corticosteroids are occasionally required and some patients require long term corticosteroids. In these instances, steroid sparing disease modify treatments are in demand. We describe a 13-year-old girl with IgG4 related systemic disease who presented with chronic recurrent autoimmune pancreatitis resulting in surgical intervention for obstructive hyperbilirubinemia and chronic corticosteroid treatment. In addition, she developed fibrosing medianstinitis as part of her IgG4 related systemic disease. She was eventually successfully treated with mycophenolate mofetil allowing for discontinuation of corticosteroids. This is the first reported use of mycophenolate mofetil for IgG4 related pancreatitis. Although autoimmune pancreatitis as part of IgG4 related systemic disease is rarely reported in pediatrics, autoimmune pancreatitis is also characterized as idiopathic fibrosing pancreatitis. All pediatric autoimmune pancreatitis cases reported in the world medical literature were identified via a PUBMED search and are reviewed herein. Twelve reports of pediatric autoimmune pancreatitis were identified, most of which were treated with corticosteroids or surgical approaches. Most case reports failed to report IgG4 levels, so it remains unclear how commonly IgG4 related autoimmune pancreatitis occurs during childhood. Increased evaluation of IgG4 levels in patients with autoimmune pancreatitis may shed further light on the association of IgG4 with pancreatitis and the underlying pathophysiology.

  13. Assessment of toxicity on chelating agent DTPA (diethylenetriaminepentaacetic acid)

    International Nuclear Information System (INIS)

    Fukuda, Satoshi

    1989-01-01

    DTPA (diethylenetriaminepentaacetic acid) is a very important chelating agent to decorporate the radionuclides such as plutonium and americium from human body. However, before DTPA will be administered to humans, the toxicity should be clarified. This report described the summary on data of DTPA toxicities obtained from animal experiments and assessment on the safety for humans, based on the results that compared their data among animal species. In short, Ca-DTPA is less toxic than Zn-DTPA when it is injected intravenously, while Zn-DTPA is less toxic than Ca-DTPA when it is administered orally. Both DTPAs acted on the serum calcium metabolism and induced the functional damages of cardiovascular system. Particularly, it is stressed that Zn-DTPA by intravenous injection occurred the heart failure, increases of blood pressure and pulse with hypocalcemia in even normal rats and beagle dogs. Other side effects by both DTPAs were also observed in the intestine, liver, kidney and bone. It is estimated that there are almost no species differences on DTPA toxicity between animals and humans. As a result, it is concluded that DTPA should be used very carefully for humans, with reference to the results obtained from animal experiments. (author) 61 refs

  14. Assessment of toxicity on chelating agent DTPA (diethylenetriaminepentaacetic acid)

    Energy Technology Data Exchange (ETDEWEB)

    Fukuda, Satoshi (National Inst. of Radiological Sciences, Chiba (Japan))

    1989-09-01

    DTPA (diethylenetriaminepentaacetic acid) is a very important chelating agent to decorporate the radionuclides such as plutonium and americium from human body. However, before DTPA will be administered to humans, the toxicity should be clarified. This report described the summary on data of DTPA toxicities obtained from animal experiments and assessment on the safety for humans, based on the results that compared their data among animal species. In short, Ca-DTPA is less toxic than Zn-DTPA when it is injected intravenously, while Zn-DTPA is less toxic than Ca-DTPA when it is administered orally. Both DTPAs acted on the serum calcium metabolism and induced the functional damages of cardiovascular system. Particularly, it is stressed that Zn-DTPA by intravenous injection occurred the heart failure, increases of blood pressure and pulse with hypocalcemia in even normal rats and beagle dogs. Other side effects by both DTPAs were also observed in the intestine, liver, kidney and bone. It is estimated that there are almost no species differences on DTPA toxicity between animals and humans. As a result, it is concluded that DTPA should be used very carefully for humans, with reference to the results obtained from animal experiments. (author) 61 refs.

  15. Topical antifungal agents: an update.

    Science.gov (United States)

    Diehl, K B

    1996-10-01

    So many topical antifungal agents have been introduced that it has become very difficult to select the proper agent for a given infection. Nonspecific agents have been available for many years, and they are still effective in many situations. These agents include Whitfield's ointment, Castellani paint, gentian violet, potassium permanganate, undecylenic acid and selenium sulfide. Specific antifungal agents include, among others, the polyenes (nystatin, amphotericin B), the imidazoles (metronidazole, clotrimazole) and the allylamines (terbinafine, naftifine). Although the choice of an antifungal agent should be based on an accurate diagnosis, many clinicians believe that topical miconazole is a relatively effective agent for the treatment of most mycotic infections. Terbinafine and other newer drugs have primary fungicidal effects. Compared with older antifungal agents, these newer drugs can be used in lower concentrations and shorter therapeutic courses. Studies are needed to evaluate the clinical efficacies and cost advantages of both newer and traditional agents.

  16. Agent-based model of fecal microbial transplant effect on bile acid metabolism on suppressing Clostridium difficile infection: an example of agent-based modeling of intestinal bacterial infection.

    Science.gov (United States)

    Peer, Xavier; An, Gary

    2014-10-01

    Agent-based modeling is a computational modeling method that represents system-level behavior as arising from multiple interactions between the multiple components that make up a system. Biological systems are thus readily described using agent-based models (ABMs), as multi-cellular organisms can be viewed as populations of interacting cells, and microbial systems manifest as colonies of individual microbes. Intersections between these two domains underlie an increasing number of pathophysiological processes, and the intestinal tract represents one of the most significant locations for these inter-domain interactions, so much so that it can be considered an internal ecology of varying robustness and function. Intestinal infections represent significant disturbances of this internal ecology, and one of the most clinically relevant intestinal infections is Clostridium difficile infection (CDI). CDI is precipitated by the use of broad-spectrum antibiotics, involves the depletion of commensal microbiota, and alterations in bile acid composition in the intestinal lumen. We present an example ABM of CDI (the C. difficile Infection ABM, or CDIABM) to examine fundamental dynamics of the pathogenesis of CDI and its response to treatment with anti-CDI antibiotics and a newer treatment therapy, fecal microbial transplant. The CDIABM focuses on one specific mechanism of potential CDI suppression: commensal modulation of bile acid composition. Even given its abstraction, the CDIABM reproduces essential dynamics of CDI and its response to therapy, and identifies a paradoxical zone of behavior that provides insight into the role of intestinal nutritional status and the efficacy of anti-CDI therapies. It is hoped that this use case example of the CDIABM can demonstrate the usefulness of both agent-based modeling and the application of abstract functional representation as the biomedical community seeks to address the challenges of increasingly complex diseases with the goal of

  17. The effect of dual complexing agents of lactic and citric acids on the formation of sol-gel derived Ag–PbTiO3 percolative thin film

    International Nuclear Information System (INIS)

    Su, Yanbo; Hu, Tao; Tang, Liwen; Weng, Wenjian; Han, Gaorong; Ma, Ning; Du, Piyi

    2014-01-01

    Controlling the formation of conductive particles to be nano-scale is important for achieving percolation effect in metal dispersed thin film composite to contribute extraordinary dielectric properties required for miniaturization of electronic devices. In this paper, lactic acid (LA) and citric acid (CA) were used as dual complexing agents to prepare a typical Ag nanoparticle dispersed PbTiO 3 (PTO) composite thin film by using a sol-gel method. The phase structure of the thin film and the coordination effect between complexing agent and metallic ions were investigated. It revealed that LA coordinated with Ti 4+ and Pb 2+ and CA coordinated with Ag + . Lead was fixed inside the gel network by LA and restricted to evaporate during heat treatment thus the pyrochlore phase was prevented from forming in the thin film. Ag + was coordinated by CA and the diffusion and thus aggregation of silver during gelation and annealing process were weakened. Silver nanoparticles dispersed in the PTO matrix formed with dual complexing agents of LA and CA introduced during the preparation process. The composite thin film of perfect perovskite phase with silver nanoparticles embedded was obtained at the molar ratio of LA/lead = 0.5 and CA/lead = 0.5. The dielectric constant of the thin film with silver nanoparticles is 5 times higher than that without silver nanoparticles. - Highlights: • Ag nanoparticle–PbTiO 3 percolative film with high dielectric property is prepared. • Evaporation of lead was prevented by coordinating Pb with lactic acid agent. • Dual complexing agents contribute block and pinning effects to form Ag nanoparticles

  18. The sources, fate, and toxicity of chemical warfare agent degradation products.

    Science.gov (United States)

    Munro, N B; Talmage, S S; Griffin, G D; Waters, L C; Watson, A P; King, J F; Hauschild, V

    1999-01-01

    We include in this review an assessment of the formation, environmental fate, and mammalian and ecotoxicity of CW agent degradation products relevant to environmental and occupational health. These parent CW agents include several vesicants: sulfur mustards [undistilled sulfur mustard (H), sulfur mustard (HD), and an HD/agent T mixture (HT)]; nitrogen mustards [ethylbis(2-chloroethyl)amine (HN1), methylbis(2-chloroethyl)amine (HN2), tris(2-chloroethyl)amine (HN3)], and Lewisite; four nerve agents (O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX), tabun (GA), sarin (GB), and soman (GD)); and the blood agent cyanogen chloride. The degradation processes considered here include hydrolysis, microbial degradation, oxidation, and photolysis. We also briefly address decontamination but not combustion processes. Because CW agents are generally not considered very persistent, certain degradation products of significant persistence, even those that are not particularly toxic, may indicate previous CW agent presence or that degradation has occurred. Of those products for which there are data on both environmental fate and toxicity, only a few are both environmentally persistent and highly toxic. Major degradation products estimated to be of significant persistence (weeks to years) include thiodiglycol for HD; Lewisite oxide for Lewisite; and ethyl methyl phosphonic acid, methyl phosphonic acid, and possibly S-(2-diisopropylaminoethyl) methylphosphonothioic acid (EA 2192) for VX. Methyl phosphonic acid is also the ultimate hydrolysis product of both GB and GD. The GB product, isopropyl methylphosphonic acid, and a closely related contaminant of GB, diisopropyl methylphosphonate, are also persistent. Of all of these compounds, only Lewisite oxide and EA 2192 possess high mammalian toxicity. Unlike other CW agents, sulfur mustard agents (e.g., HD) are somewhat persistent; therefore, sites or conditions involving potential HD contamination should include an

  19. Enhanced drug encapsulation and extended release profiles of calcium-alginate nanoparticles by using tannic acid as a bridging cross-linking agent.

    Science.gov (United States)

    Abulateefeh, Samer R; Taha, Mutasem O

    2015-01-01

    Calcium alginate nanoparticles (NPs) suffer from sub-optimal stability in bio-relevant media leading to low drug encapsulation efficiency and uncontrolled release profiles. To sort out these drawbacks, a novel approach is proposed herein based on introducing tannic acid into these NPs to act as a bridging cross-linking aid agent. Calcium-alginate NPs were prepared by the ionotropic gelation method and loaded with diltiazem hydrochloride as a model drug. These NPs were characterized in terms of particle size, zeta potential, and morphology, and results were explained in accordance with Fourier-transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). The incorporation of tannic acid led to more than four folds increase in drug encapsulation efficiency (i.e. from 15.3% to 69.5%) and reduced burst drug release from 44% to around 10% within the first 30 min. These findings suggest the possibility of improving the properties of Ca-alginate NPs by incorporating cross-linking aid agents under mild conditions.

  20. Depletion of glutathione by the radioprotective agent S-2-(3-aminopropylamino)ethyl phosphorothioic acid (WR2721)

    International Nuclear Information System (INIS)

    Schor, N.F.

    1989-01-01

    S-2-(3-Aminopropylamino)ethyl phosphorothioic acid (WR2721) is a free radical scavenger currently in limited clinical use as an adjunct in cancer radio- and chemotherapy. We have previously determined the pharmacokinetics and protein binding characteristics of WR2721 in rabbits and in humans. We have also shown that WR2721 is an effective mucolytic agent in patients with cystic fibrosis. In vivo, WR2721 is converted to its free thiol analogue, N-2-mercaptoethyl-1,3-diaminopropane (MDP), and, as such, reacts with disulfide bonds in the mucin molecule, altering its rheology. In the course of experiments designed to examine the spectrum of its activity as a free radical scavenger, we have observed that WR2721 exacerbates the toxicity of those free radical-generating agents, such as acetaminophen and 6-hydroxydopamine, which depend upon glutathione for their detoxication. For this reason, we examined the glutathione content of the livers of mice treated with WR2721. (author)

  1. Improving Properties of Arrowroot Starch (Maranta arundinacea)/PVA Blend Films by Using Citric Acid as Cross-linking Agent

    Science.gov (United States)

    Sholichah, Enny; Purwono, Bambang; Nugroho, Pramono

    2017-12-01

    This research studied the effect of PVA as organic polymer and citric acid as crosslinker agent in the arrowroot starch/PVA blend films. The properties of films were investigated by water uptake, water vapor permeability, mechanical properties, thermal stability, spectra of FTIR and XRD patterns. PVA used in this research influenced the film properties at the highest concentration. The cross-linkingsinter or intra molecules of arrowroot and PVA were developed as ester bonds which are formed from the reaction of hydroxyl groups consisting of starch and PVA with citric acid. The ester bond was confirmed by FTIR spectra. The increase of the amount of citric acid affected significantly on physical, chemical and mechanical properties, water uptake, WVP and crystallinity. Water barrier level was reduced by decreasing of water uptake and WVP succeeded significantly with increased crosslinking. Cross-linking impact the thermal stability of the films. The elasticity of the films also increases the production of citric acid as a plasticizer in the making of the films as a food packaging material.

  2. Aminolevulinic acid-photodynamic therapy combined with topically applied vascular disrupting agent vadimezan leads to enhanced antitumor responses.

    Science.gov (United States)

    Marrero, Allison; Becker, Theresa; Sunar, Ulas; Morgan, Janet; Bellnier, David

    2011-01-01

    The tumor vascular-disrupting agent (VDA) vadimezan (5,6-dimethylxanthenone-4-acetic acid, DMXAA) has been shown to potentiate the antitumor activity of photodynamic therapy (PDT) using systemically administered photosensitizers. Here, we characterized the response of subcutaneous syngeneic Colon26 murine colon adenocarcinoma tumors to PDT using the locally applied photosensitizer precursor aminolevulinic acid (ALA) in combination with a topical formulation of vadimezan. Diffuse correlation spectroscopy (DCS), a noninvasive method for monitoring blood flow, was utilized to determine tumor vascular response to treatment. In addition, correlative CD31-immunohistochemistry to visualize endothelial damage, ELISA to measure induction of tumor necrosis factor-alpha (TNF-α) and tumor weight measurements were also examined in separate animals. In our previous work, DCS revealed a selective decrease in tumor blood flow over time following topical vadimezan. ALA-PDT treatment also induced a decrease in tumor blood flow. The onset of blood flow reduction was rapid in tumors treated with both ALA-PDT and vadimezan. CD31-immunostaining of tumor sections confirmed vascular damage following topical application of vadimezan. Tumor weight measurements revealed enhanced tumor growth inhibition with combination treatment compared with ALA-PDT or vadimezan treatment alone. In conclusion, vadimezan as a topical agent enhances treatment efficacy when combined with ALA-PDT. This combination could be useful in clinical applications. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

  3. Effect of weak acid preservatives on growth of bakery product spoilage fungi at different water activities and pH values

    DEFF Research Database (Denmark)

    Suhr, Karin Isabel; Nielsen, Per Væggemose

    2004-01-01

    moisture sponge cake types (a(w) 0.80-0.95, pH 4.7-7.4). Initially, rye bread conditions (a(w) 0.94-0.97 and pH 4.4-4.8) in combination with calcium propionate were investigated. Results showed that the highest concentration of propionate (0.3%) at all conditions apart from high a(w) (0.97) and high pH (4...... enhanced at high water activity levels. The effect of propionate on production of secondary metabolites (mycophenolic acid, rugulovasine, echinulin, flavoglaucin) was also studied, and variable or isolate dependent results were found. Subsequently, a screening experiment representing a wider range...

  4. Potential impact of policy regulation and generic competition on sales of cholesterol lowering medication, antidepressants and acid blocking agents in Belgium.

    Science.gov (United States)

    Fraeyman, J; Van Hal, G; De Loof, H; Remmen, R; De Meyer, G R Y; Beutels, P

    2012-01-01

    Pharmaceutical expenditures are increasing as a proportion of health expenditures in most rich countries. Antidepressants, acid blocking agents and cholesterol lowering medication are major contributors to medicine sales around the globe. We aimed to document the possible impact of policy regulations and generic market penetration on the evolution of sales volume and average cost per unit (Defined Daily Doses and packages) of antidepressants, acid blocking agents and cholesterol lowering medication. We extracted data from the IMS health database regarding the public price and sales volume of the antidepressants (selective serotonin reuptake inhibitors (SSRI's), monoamine oxidase inhibitors (MAOl's) and tricyclic and remaining antidepressants (TCA's)), acid blocking agents (proton pump inhibitors (PPl's) and H2 receptor antagonists) and cholesterol lowering medication (statins and fibrates) in Belgium between 1995 and 2009. We describe these sales data in relation to various national policy measures which were systematically searched in official records. Our analysis suggests that particular policy regulations have had immediate impact on sales figures and expenditures on pharmaceuticals in Belgium: changes in reimbursement conditions, a public tender and entry of generic competitors in a reference pricing system. However, possible sustainable effects seem to be counteracted by other mechanisms such as marketing strategies, prescribing behaviour, brand loyalty and the entry of pseudogenerics. It is likely that demand-side measures have a more sustainable impact on expenditure. Compared with other European countries, generic penetration in Belgium remains low. Alternative policy regulations aimed at enlarging the generic market and influencing pharmaceutical expenditures deserve consideration. This should include policies aiming to influence physicians' prescribing and a shared responsibility of pharmacists, physicians and patients towards expenditures.

  5. Comparison of solutol HS 15, Cremophor EL and novel ethoxylated fatty acid surfactants as multidrug resistance modification agents.

    Science.gov (United States)

    Buckingham, L E; Balasubramanian, M; Emanuele, R M; Clodfelter, K E; Coon, J S

    1995-08-09

    Some well-known fatty acid ester surfactants, e.g., Cremophor EL and Solutol HS 15, are modulators of multidrug resistance in vitro and in vivo. Because they are polydisperse, and their active component(s) have not been identified, the therapeutic potential of such surfactants is unclear. To better define the active components of Solutol HS 15 and to make more potent surfactant multidrug resistance modulators, highly purified C-18 fatty acids were esterified with ethylene oxide at 5-200 molar ratios. Unexpectedly, ethylene oxide esters of pure 12-hydroxy stearic acid, the major components of Solutol HS 15, displayed negligible resistance modification activity compared with Solutol HS 15 itself or to stearic and oleic acid esters synthesized under identical conditions. Since oleic acid esters appeared to have good activity, a series of these compounds was prepared to determine the optimal ethylene oxide/fatty acid ratio. The optimal ratio was found to be 20 mole ethylene oxide: I mole fatty acid, with a steep decline in activity for products made with ratios above and below the optimum. The most active oleic acid ester, designated CRL 1337, was 8.4-fold as potent as Solutol HS 15 and over 19-fold as potent as Cremophor EL in promoting rhodamine 123 accumulation in multidrug-resistant KB 8-5-11 cells in vitro. Our results show that the structure of the hydrophobic domain (fatty acid) of surfactants as well as its hydrophile-lipophile balance are critical in determining the potency of surfactants as reversing agents.

  6. Fatty acid is a potential agent for bone tissue induction: In vitro and in vivo approach.

    Science.gov (United States)

    Cardoso, Guinea Bc; Chacon, Erivelto; Chacon, Priscila Gl; Bordeaux-Rego, Pedro; Duarte, Adriana Ss; Saad, Sara T Olalla; Zavaglia, Cecilia Ac; Cunha, Marcelo R

    2017-12-01

    Our hypothesis was to investigate the fatty acid potential as a bone induction factor. In vitro and in vivo studies were performed to evaluate this approach. Oleic acid was used in a 0.5 wt.% concentration. Polycaprolactone was used as the polymeric matrix by combining solvent-casting and particulate-leaching techniques, with a final porosity of 70 wt.%, investigated by SEM images. Contact angle measurements were produced to investigate the influence of oleic acid on polycaprolactone chains. Cell culture was performed using adipocyte-derived stem cells to evaluate biocompatibility and bioactivity properties. In addition, in vivo studies were performed to evaluate the induction potential of oleic acid addition. Adipocyte-derived stem cells were used to provide differentiation after 21 days of culture. Likewise, information were obtained with in vivo data and cellular invagination was observed on both scaffolds (polycaprolactone and polycaprolactone /oleic acid); interestingly, the scaffold with oleic acid addition demonstrated that cellular migrations are not related to the surrounding tissue, indicating bioactive potential. Our hypothesis is that fatty acid may be used as a potential induction factor for bone tissue engineering. The study's findings indicate oleic acid as a possible agent for bone induction, according to data on cell differentiation, proliferation, and migration. Impact statement The biomaterial combined in this study on bone regeneration is innovative and shows promising results in the treatment of bone lesions. Polycaprolactone (PCL) and oleic acid have been studied separately. In this research, we combined biomaterials to assess the stimulus and the speed of bone healing.

  7. The use of desorbing agents in electrodialytic remediation of harbour sediment

    DEFF Research Database (Denmark)

    Nystrøm, Gunvor Marie; Pedersen, Anne Juul; Ottosen, Lisbeth M.

    2006-01-01

    Electrodialytic removal of Cu, Zn, Pb and Cd from contaminated harbour sediment was made with the emphasis of testing the effectiveness of different desorbing agents: HCl, NaCl, citric acid, lactic acid, ammonium citrate and distilled water. Extraction experiments with the desorbing agents were...

  8. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    Raheem, Omer A

    2011-05-28

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  9. Mycophenolate mofetil in low-risk renal transplantation in patients receiving no cyclosporine: a single-centre experience.

    LENUS (Irish Health Repository)

    2012-02-01

    BACKGROUND: We assess our long-term experience with regards the safety and efficacy of Mycophenolate Mofetil (MMF) in our low risk renal transplant population and compared it retrospectively to Azathioprine (AZA) immunosuppressive regimen. Patients and methods. Between January 1999 and December 2005, 240 renal transplants received MMF as part of their immunosuppressive protocol (MMF group). AZA group of 135 renal transplants was included for comparative analysis (AZA group). Patients received Cyclosporine was excluded from this study. RESULTS: The incidence of biopsy proven 3-month acute rejections was 30 (12.5%) in MMF group and 22 (16%) in AZA group respectively (P = 0.307). Patient survival rates at 1 and 5 years for the MMF group were 97 and 94%, respectively, compared to 100% and 91% at 1 and 5 years respectively for the AZA group (P = 0.61). Graft survival rates at 1 and 5 years for the MMF group were 95 and 83%, respectively, compared to 97 and 84% at 1 and 5 years, respectively for the AZA group (P = 0.62). CONCLUSION: There was no difference in acute rejection episodes between MMF and AZA based immunotherapy. Additionally, we observed no significant difference concerning graft survival in the MMF group when compared to AZA group.

  10. 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

    Science.gov (United States)

    Hayakawa, Ichiro; Shioya, Rieko; Agatsuma, Toshinori; Furukawa, Hidehiko; Naruto, Shunji; Sugano, Yuichi

    2004-01-19

    Based on the structure of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which exhibits selective cytotoxicity against a tumorigenic cell line, (2,4-dimethoxyphenyl)-(4-hydroxy-3-methyl-6-phenylbenzofuran-2-yl)-methanone (18m) was designed and synthesized as a biologically stable derivative containing no ester group. Although the potency of 18m was almost the same as our initial hit compound 1, 18m is expected to last longer in the human body as an anticancer agent.

  11. Effect and Removal Mechanisms of 6 Different Washing Agents for Building Wastes Containing Chromium

    Directory of Open Access Journals (Sweden)

    Wang Xing-run

    2012-01-01

    Full Text Available With the building wastes contaminated by chromium in Haibei Chemical Plan in China as objects, we studied the contents of total Cr and Cr (VI of different sizes, analyzed the effect of 6 different washing agents, discussed the removal mechanisms of 6 different washing agents for Cr in various forms, and finally selected applicable washing agent. As per the results, particle size had little impact on the contents of total Cr and Cr (VI; after one washing with water, the removal rate of total Cr and Cr (VI was 75% and 78%, respectively, and after the second washing with 6 agents, the removal rate of citric acid was the highest, above 90% for total Cr and above 99% for hexavalent chromium; the pH of building wastes were reduced by citric acid, and under acid condition, hexavalent chromium was reduced to trivalent chromium spontaneously by organic acid, which led to better removal rate of acid soluble Cr and reducible Cr; due to the complexing action, citric acid had best removal rate for oxidizable trivalent chromium. In conclusion, citric acid is the most applicable second washing agent for building wastes.

  12. Brevianamides and Mycophenolic Acid Derivatives from the Deep-Sea-Derived Fungus Penicillium brevicompactum DFFSCS025

    Directory of Open Access Journals (Sweden)

    Xinya Xu

    2017-02-01

    Full Text Available Four new compounds (1–4, including two brevianamides and two mycochromenic acid derivatives along with six known compounds were isolated from the deep-sea-derived fungus Penicillium brevicompactum DFFSCS025. Their structures were elucidated by spectroscopic analysis. Moreover, the absolute configurations of 1 and 2 were determined by quantum chemical calculations of the electronic circular dichroism (ECD spectra. Compound 9 showed moderate cytotoxicity against human colon cancer HCT116 cell line with IC50 value of 15.6 μM. In addition, 3 and 5 had significant antifouling activity against Bugula neritina larval settlement with EC50 values of 13.7 and 22.6 μM, respectively. The NMR data of 6, 8, and 9 were assigned for the first time.

  13. Current methods of the analysis of immunosuppressive agents in clinical materials: A review.

    Science.gov (United States)

    Mika, Adriana; Stepnowski, Piotr

    2016-08-05

    More than 100000 solid organ transplantations are performed every year worldwide. Calcineurin (cyclosporine A, tacrolimus), serine/threonine kinase (sirolimus, everolimus) and inosine monophosphate dehydrogenase inhibitor (mycophenolate mofetil), are the most common drugs used as immunosuppressive agents after solid organ transplantation. Immunosuppressive therapy, although necessary after transplantation, is associated with many adverse consequences, including the formation of secondary metabolites of drugs and the induction of their side effects. Calcineurin inhibitors are associated with nephrotoxicity, cardiotoxicity and neurotoxicity; moreover, they increase the risk of many diseases after transplantation. The review presents a study of the movement of drugs in the body, including the processes of absorption, distribution, localisation in tissues, biotransformation and excretion, and also their accompanying side effects. Therefore, there is a necessity to monitor immunosuppressants, especially because these drugs are characterised by narrow therapeutic ranges. Their incorrect concentrations in a patient's blood could result in transplant rejection or in the accumulation of toxic effects. Immunosuppressive pharmaceuticals are macrolide lactones, peptides, and high molecular weight molecules that can be metabolised to several metabolites. Therefore the two main analytical methods used for their determination are high performance liquid chromatography with various detection methods and immunoassay methods. Despite the rapid development of new analytical methods of analysing immunosuppressive agents, the application of the latest generation of detectors and increasing sensitivity of such methods, there is still a great demand for the development of highly selective, sensitive, specific, rapid and relatively simple methods of immunosuppressive drugs analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Stabilized radiographic scanning agent

    International Nuclear Information System (INIS)

    Fawzi, M.B.

    1979-01-01

    A stable composition useful in preparation of technetium-99m-based radiographic scanning agents has been developed. The composition contains a stabilizing amount of gentisate stabilizer selected from gentisic acid and its soluble pharmaceutically-acceptable salts and esthers. (E.G.)

  15. Transient phytoextraction agents: establishing criteria for the use of chelants in phytoextraction of recalcitrant metals.

    Science.gov (United States)

    Parra, R; Ulery, A L; Elless, M P; Blaylock, M J

    2008-01-01

    The phytoremediation of recalcitrant metals such as lead and uranium rely on soil amendments to enhance metal availability within the rhizosphere. Because these amendments may persist in soils, agents that not only biodegrade rapidly but also are effective in triggering metal uptake in plants are needed for metals phytoextraction to be considered as an accepted practice. In this study, several biodegradable organic acids and chelating agents were assessed to determine if these amendments can be used in an effective manner, and if their activity and use is consistent with a proposed class of soil amendments for phytoextraction, here termed transient phytoextraction agents (TPAs). A TPA is proposed as an agent that would exhibit both effectiveness in triggering plant accumulation of the targeted metal while minimizing the risk of migration through rapid degradation or inactivation of the soluble complex. Eleven candidate TPAs (acetic acid, ascorbic acid, citric acid, malic acid, oxalic acid, succinic acid, ethylenediaminedisuccinic acid, dicarboxymethylglutamic acid, nitrilotriacetic acid, BayPure CX 100, and the siderophore desferrioxamine B) were tested in batch studies to evaluate their complexation behavior using contaminated soils, with uranium and lead as the target metals. A growth chamber study was then conducted with Brassica juncea (Indian mustard), Helianthus annuus (sunflower), and Festuca arundinacea (tall fescue) grown in a lead-contaminated soil that was treated with the candidate TPAs to assess phytoextraction effectiveness. For the soils tested, citric acid, oxalic acid, and succinic acid were found to be effective complexing agents for uranium phytoextraction, whereas Baypure CX 100 and citric acid exhibited effectiveness for lead phytoextraction.

  16. ACETIC ACID AND A BUFFER

    DEFF Research Database (Denmark)

    2009-01-01

    The present invention relates to a composition comprising : a) 0.01-20% wt/wt acetic acid and b) a physiologically tolerable buffer capable of maintaining acetic acid at a pH in the range of 2-7; and use of such a composition as an antimicrobial agent.......The present invention relates to a composition comprising : a) 0.01-20% wt/wt acetic acid and b) a physiologically tolerable buffer capable of maintaining acetic acid at a pH in the range of 2-7; and use of such a composition as an antimicrobial agent....

  17. 42 CFR 73.3 - HHS select agents and toxins.

    Science.gov (United States)

    2010-10-01

    ... been genetically modified. (d) HHS select agents or toxins that meet any of the following criteria are... Recombinant Organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses...

  18. Comparison of the efficacy of ethylenediaminetetraacetic acid and tetracycline hydrochloride as root conditioning agents: An in vitro study

    Directory of Open Access Journals (Sweden)

    Tarun Nanda

    2012-01-01

    Full Text Available Objective: Root surfaces of periodontitis-affected teeth are hypermineralized and contaminated with cytotoxic and other biologically active substances. Various root conditioning agents have been recommended as an adjunct to mechanical root surface debridement to expose dentin collagen and cementum bound proteins. The aim of the present in vitro study was to compare the efficacy of ethylenediaminetetraacetic acid (EDTA and tetracycline hydrochloride (HCl as root conditioning agents on planed root surfaces. Materials and Methods: A total of 20 human maxillary anterior teeth indicated for extraction due to chronic periodontitis were collected and root planed. The teeth were sectioned and specimens were divided into two groups - Group I and II. Group I dentin specimens were treated with EDTA and Group II specimens were treated with tetracycline HCl solution at a concentration of 10% by active burnishing technique for 3 min. The root surface samples were then examined by scanning electron microscope. Results: The results of this study showed that EDTA and tetracycline HCl were equally effective in removing the smear layer. It was observed that the total and patent dentinal tubules were more in number in teeth treated with tetracycline when compared to EDTA group. However, EDTA was found to be much more effective as root conditioning agent because it enlarged the diameter of dentinal tubules more than that of tetracycline HCl. Conclusion: The results of in vitro study showed that both the agents are good root conditioning agents if applied in addition to periodontal therapy. However, further studies are required to establish the in vivo importance of EDTA and tetracycline HCL as root conditioners.

  19. Synthesis and tissue distribution of fluorine-18 labeled trifluorohexadecanoic acids. Considerations in the development of metabolically blocked myocardial imaging agents

    International Nuclear Information System (INIS)

    Pochapsky, S.S.; Katzenellenbogen, J.A.; VanBrocklin, H.F.; Welch, M.J.

    1990-01-01

    A versatile method for the synthesis of trifluoro fatty acids, potential metabolically blocked myocardial imaging agents, has been developed. Two trifluorohexadecanoic (palmitic) acids have been prepared [6,6,16-trifluorohexadecanoic acid (I) and 7,7,16-trifluorohexadecanoic acid (II)], each of which bears two of the fluorine atoms as a gem-difluoromethylene unit on the fatty acid chain (at C-6 or C-7) and the third at the ω (C-16) position. The metabolic stability of carbon-fluorine bonds suggests the gem-difluoro group may block the β-oxidation pathway, while the terminal fluorine could be the site for labeling with fluorine-18. The convergent synthetic approach utilizes a 2-lithio-1,3-dithiane derived from 10-undecenal or 9-decenal, which is alkylated with the OBO (oxabicyclooctyl) ester of 5-bromopentanoic acid or 6-bromohexanoic acid, respectively. Hydroboration-oxidation and alcohol protection are followed by halofluorination to convert the 1,3-dithiane system to a gem-difluoro group. The third fluorine is introduced by fluoride ion displacement of a trifluoromethanesulfonate. This synthesis is adapted to the labeling of these trifluoro fatty acids with the short-lived radionuclide fluorine-18 (t 1/2 = 110 min), with the third fluorine introduced as fluoride ion in the penultimate step. The radiochemical syntheses proceed in 3-34% radiochemical yield (decay corrected), with an overall synthesis and purification time of 90 min. Tissue distribution studies in rats were performed with I and II, as well as with 16-[ 18 F]fluoropalmitic acid (III), [ 11 C]palmitic acid, and [ 11 C]octanoic acid. The heart uptake of the fluoropalmitic acids decreases with substitution, the 2-min activity level for 16-fluoropalmitic acid being 65% and that for both 6,6,16-and 7,7,17-trifluoropalmitic acids being 30% that of palmitic acid

  20. 聚乳酸有机成核剂研究进展%Research Process in Organic Nucleating Agent of Poly (lactic acid)

    Institute of Scientific and Technical Information of China (English)

    李丽

    2014-01-01

    聚乳酸作为生物可降解材料应用广泛,但是结晶速率非常慢,添加成核剂可以改善其结晶速率,其中有机成核剂因其与聚乳酸良好的相容性备受关注。本文重点综述了有机成核剂的种类及其对聚乳酸结晶性能的改善情况,并展望了有机成核剂今后的发展方向。%Poly (lactic acid) (PLA) was widely used as main biodegradable plastics. Adding nucleating agent was an effective way of improving crystallization rate. Due to its good compatibility with PLA, the organic nucleating agent had drawn much attention. The types of organic nucleating agent were reviewed. Finally, the research work of organic nucleating agent in the future was predicted.

  1. Inhibitors of amino acids biosynthesis as antifungal agents.

    Science.gov (United States)

    Jastrzębowska, Kamila; Gabriel, Iwona

    2015-02-01

    Fungal microorganisms, including the human pathogenic yeast and filamentous fungi, are able to synthesize all proteinogenic amino acids, including nine that are essential for humans. A number of enzymes catalyzing particular steps of human-essential amino acid biosynthesis are fungi specific. Numerous studies have shown that auxotrophic mutants of human pathogenic fungi impaired in biosynthesis of particular amino acids exhibit growth defect or at least reduced virulence under in vivo conditions. Several chemical compounds inhibiting activity of one of these enzymes exhibit good antifungal in vitro activity in minimal growth media, which is not always confirmed under in vivo conditions. This article provides a comprehensive overview of the present knowledge on pathways of amino acids biosynthesis in fungi, with a special emphasis put on enzymes catalyzing particular steps of these pathways as potential targets for antifungal chemotherapy.

  2. Uranium recovery from wet process phosphoric acid

    International Nuclear Information System (INIS)

    Carrington, O.F.; Pyrih, R.Z.; Rickard, R.S.

    1981-01-01

    Improvement in the process for recovering uranium from wetprocess phosphoric acid solution derived from the acidulation of uraniferous phosphate ores by the use of two ion exchange liquidliquid solvent extraction circuits in which in the first circuit (A) the uranium is reduced to the uranous form; (B) the uranous uranium is recovered by liquid-liquid solvent extraction using a mixture of mono- and di-(Alkyl-phenyl) esters of orthophosphoric acid as the ion exchange agent; and (C) the uranium oxidatively stripped from the agent with phosphoric acid containing an oxidizing agent to convert uranous to uranyl ions, and in the second circuit (D) recovering the uranyl uranium from the strip solution by liquid-liquid solvent extraction using di(2ethylhexyl)phosphoric acid in the presence of trioctylphosphine oxide as a synergist; (E) scrubbing the uranium loaded agent with water; (F) stripping the loaded agent with ammonium carbonate, and (G) calcining the formed ammonium uranyl carbonate to uranium oxide, the improvement comprising: (1) removing the organics from the raffinate of step (B) before recycling the raffinate to the wet-process plant, and returning the recovered organics to the circuit to substantially maintain the required balance between the mono and disubstituted esters; (2) using hydogren peroxide as the oxidizing agent in step (C); (3) using an alkali metal carbonate as the stripping agent in step (F) following by acidification of the strip solution with sulfuric acid; (4) using some of the acidified strip solution as the scrubbing agent in step (E) to remove phosphorus and other impurities; and (5) regenerating the alkali metal loaded agent from step (F) before recycling it to the second circuit

  3. Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

    Science.gov (United States)

    Daryaei, Iman; Pagel, Mark D

    2015-01-01

    Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

  4. Short-chain fatty acids and poly-beta-hydroxyalkanoates: (New) Biocontrol agents for a sustainable animal production.

    Science.gov (United States)

    Defoirdt, Tom; Boon, Nico; Sorgeloos, Patrick; Verstraete, Willy; Bossier, Peter

    2009-01-01

    Because of the risk of antibiotic resistance development, there is a growing awareness that antibiotics should be used more carefully in animal production. However, a decreased use of antibiotics could result in a higher frequency of pathogenic bacteria, which in its turn could lead to a higher incidence of infections. Short-chain fatty acids (SCFAs) have long been known to exhibit bacteriostatic activity. These compounds also specifically downregulate virulence factor expression and positively influence the gastrointestinal health of the host. As a consequence, there is currently considerable interest in SCFAs as biocontrol agents in animal production. Polyhydroxyalkanoates (PHAs) are polymers of beta-hydroxy short-chain fatty acids. Currently, PHAs are applied as replacements for synthetic polymers. These biopolymers can be depolymerised by many different microorganisms that produce extracellular PHA depolymerases. Interestingly, different studies provided some evidence that PHAs can also be degraded upon passage through the gastrointestinal tract of animals and consequently, adding these compounds to the feed might result in biocontrol effects similar to those described for SCFAs.

  5. Efficacy of Lactic Acid, Lactic Acid-Acetic Acid Blends, and Peracetic Acid To Reduce Salmonella on Chicken Parts under Simulated Commercial Processing Conditions.

    Science.gov (United States)

    Ramirex-Hernandez, Alejandra; Brashears, Mindy M; Sanchez-Plata, Marcos X

    2018-01-01

    The poultry processing industry has been undergoing a series of changes as it modifies processing practices to comply with new performance standards for chicken parts and comminuted poultry products. The regulatory approach encourages the use of intervention strategies to prevent and control foodborne pathogens in poultry products and thus improve food safety and protect human health. The present studies were conducted to evaluate the efficacy of antimicrobial interventions for reducing Salmonella on inoculated chicken parts under simulated commercial processing conditions. Chicken pieces were inoculated by immersion in a five-strain Salmonella cocktail at 6 log CFU/mL and then treated with organic acids and oxidizing agents on a commercial rinsing conveyor belt. The efficacy of spraying with six different treatments (sterile water, lactic acid, acetic acid, buffered lactic acid, acetic acid in combination with lactic acid, and peracetic acid) at two concentrations was evaluated on skin-on and skin-off chicken thighs at three application temperatures. Skinless chicken breasts were used to evaluate the antimicrobial efficacy of lactic acid and peracetic acid. The color stability of treated and untreated chicken parts was assessed after the acid interventions. The lactic acid and buffered lactic acid treatments produced the greatest reductions in Salmonella counts. Significant differences between the control and water treatments were identified for 5.11% lactic acid and 5.85% buffered lactic acid in both skin-on and skin-off chicken thighs. No significant effect of treatment temperature for skin-on chicken thighs was found. Lactic acid and peracetic acid were effective agents for eluting Salmonella cells attached to chicken breasts.

  6. Treatment of acid mine wastewaters

    International Nuclear Information System (INIS)

    Hayward, D.; Barnard, R.

    1993-01-01

    Acid mine drainage often results from the oxidation sulfide minerals to form sulfuric acid. As a consequence, high concentrations of metals in the both the suspended and dissolved state result from the low pH water. This paper discusses several of the more common treatment methods for acid mine drainage including the use of chemical precipitation agents, pH correction agents, filtration methods, and biodegradation methods. Advanced treatment technologies are also briefly described and include microfiltration, reverse osmosis, ion exchange, and electrodialysis

  7. Evaluation of Ga-DOTA-(D-Asp)n as bone imaging agents: D-aspartic acid peptides as carriers to bone.

    Science.gov (United States)

    Ogawa, Kazuma; Ishizaki, Atsushi; Takai, Kenichiro; Kitamura, Yoji; Makino, Akira; Kozaka, Takashi; Kiyono, Yasushi; Shiba, Kazuhiro; Odani, Akira

    2017-10-25

    67 Ga-DOTA-(L-Asp) 11 and 67 Ga-DOTA-(L-Asp) 14 , which have been developed as bone imaging agents, showed a high accumulation in bone and a rapid blood clearance in mice. However, peptides composed of D-amino acids are more stable in vivo than those composed of their L-equivalents. In this study, 67 Ga-DOTA-(D-Asp) n (n = 2, 5, 8, 11, or 14) were synthesized using the Fmoc-based solid-phase methodology and evaluated. In hydroxyapatite binding assay, binding of 67 Ga-DOTA-(D-Asp) n tended to increase with increasing length of the amino acid chain. 67 Ga-DOTA-(D-Asp) 11 and 67 Ga-DOTA-(D-Asp) 14 caused a high accumulation of radioactivity in the bones of the mice. However, the results for 67 Ga-DOTA-(D-Asp) n and 67 Ga-DOTA-(L-Asp) n were comparable. In urine analyses, the proportion of intact complex after injection of 67 Ga-DOTA-(D-Asp) 14 was significantly higher than that of 67 Ga-DOTA-(L-Asp) 14 . Although 67 Ga-DOTA-(D-Asp) 14 was more stable than 67 Ga-DOTA-(L-Asp) 14 , the properties of 67 Ga-DOTA-(D-Asp) n and 67 Ga-DOTA-(L-Asp) n as bone imaging agents may be comparable.

  8. Understanding risk evaluation and mitigation strategies in organ transplantation.

    Science.gov (United States)

    Gabardi, Steven

    2011-07-01

    The United States Food and Drug Administration (FDA) Amendments Act of 2007 mandated that Risk Evaluation and Mitigation Strategies (REMS) be required of manufacturers. These REMS are strategies implemented to manage known or potential risks associated with drugs and to ensure ongoing pharmacovigilance throughout the life of a pharmaceutical product, including once the product becomes available as generic. The elements of an individual REMS program consist of three levels: medication guide or patient package insert, communication plan, and elements to assure safe use (ETASU). A medication guide or patient package insert is used to help prevent serious adverse events, aid in patient decision making, and enhance drug adherence. Communication plans are used to educate health care providers and to encourage their compliance with REMS. The ETASU is a restrictive process that is implemented when it is deemed necessary to ensure that patients have safe access to products with known serious risks that would otherwise be unavailable. To review the components of REMS and specifically assess their impact on health care providers practicing within the organ transplantation arena, a literature search of the MEDLINE database (January 2007-December 2010) was performed, and published materials from the FDA and its Web site were also reviewed. In transplantation, REMS programs exist for both everolimus (medication guide and communication plan) and sirolimus (medication guide). The FDA has stated that all mycophenolic acid derivatives will be subject to a proposed REMS that has not yet been approved; however, both branded mycophenolic acid agents already have approved medication guides. The REMS are a permanent fixture in the development and marketing of pharmaceutical agents, and their further implementation in solid organ transplantation is inevitable. Transplantation providers should take a proactive role in patient education and implementation of REMS within the therapeutic area

  9. 99mTc renal tubular function agents: Current status

    International Nuclear Information System (INIS)

    Eshima, D.; Fritzberg, A.R.; Taylor, A. Jr.

    1990-01-01

    Orthoiodohippuric (OIH) acid labeled with 131I is a widely used renal radiopharmaceutical agent and has been the standard radiopharmaceutical agent for the measurement of effective renal plasma flow (EPRF). Limitations to the routine clinical use of 131I OIH are related to the suboptimal imaging properties of the 131I radionuclide and its relatively high radiation dose. 123I has been substituted for 131I; however, its high cost and short shelf-life have limited its widespread use. Recent work has centered on the development of a new 99mTc renal tubular function agent, which would use the optimal radionuclidic properties and availability of 99mTc and combine the clinical information provided by OIH. The search for a suitable 99mTc renal tubular function agent has focused on the diamide dithiolate (N2S2), the paraaminohippuric iminodiacetic acid (PAHIDA), and the triamide mercaptide (N3S) donor ligand systems. To date, the most promising 99mTc tubular function agent is the N3S complex: 99mTc mercaptoacetyltriglycine (99mTc MAG3). Studies in animal models in diuresis, dehydration, acid or base imbalance, ischemia, and renal artery stenosis demonstrate that 99mTc MAG3 behaves similarly to 131I OIH. A simple kit formulation is available that yields the 99mTc MAG3 complex in high radiochemical purity. Studies in normal subjects and patients indicate that 99mTc MAG3 is an excellent 99mTc renal tubular agent, but its plasma clearance is only 50% to 60% that of OIH. In an effort to develop an improved 99mTc renal tubular function agent, changes have been made in the core N3S donor ligand system, but to date no agent has been synthesized that is clinically superior to 99mTc MAG3. 61 references

  10. Membrane extraction with thermodynamically unstable diphosphonic acid derivatives

    Science.gov (United States)

    Horwitz, E.P.; Gatrone, R.C.; Nash, K.L.

    1997-10-14

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described. 1 fig.

  11. α-Linolenic Acid, A Nutraceutical with Pleiotropic Properties That Targets Endogenous Neuroprotective Pathways to Protect against Organophosphate Nerve Agent-Induced Neuropathology

    Directory of Open Access Journals (Sweden)

    Tetsade Piermartiri

    2015-11-01

    Full Text Available α-Linolenic acid (ALA is a nutraceutical found in vegetable products such as flax and walnuts. The pleiotropic properties of ALA target endogenous neuroprotective and neurorestorative pathways in brain and involve the transcription factor nuclear factor kappa B (NF-κB, brain-derived neurotrophic factor (BDNF, a major neuroprotective protein in brain, and downstream signaling pathways likely mediated via activation of TrkB, the cognate receptor of BDNF. In this review, we discuss possible mechanisms of ALA efficacy against the highly toxic OP nerve agent soman. Organophosphate (OP nerve agents are highly toxic chemical warfare agents and a threat to military and civilian populations. Once considered only for battlefield use, these agents are now used by terrorists to inflict mass casualties. OP nerve agents inhibit the critical enzyme acetylcholinesterase (AChE that rapidly leads to a cholinergic crisis involving multiple organs. Status epilepticus results from the excessive accumulation of synaptic acetylcholine which in turn leads to the overactivation of muscarinic receptors; prolonged seizures cause the neuropathology and long-term consequences in survivors. Current countermeasures mitigate symptoms and signs as well as reduce brain damage, but must be given within minutes after exposure to OP nerve agents supporting interest in newer and more effective therapies. The pleiotropic properties of ALA result in a coordinated molecular and cellular program to restore neuronal networks and improve cognitive function in soman-exposed animals. Collectively, ALA should be brought to the clinic to treat the long-term consequences of nerve agents in survivors. ALA may be an effective therapy for other acute and chronic neurodegenerative disorders.

  12. In vitro cytotoxicity of fungi spoiling maize silage

    DEFF Research Database (Denmark)

    Rasmussen, Rie Romme; Rasmussen, Peter Have; Larsen, Thomas Ostenfeld

    2011-01-01

    Penicillium roqueforti, Penicillium paneum, Monascus ruber, Alternaria tenuissima, Fusarium graminearum, Fusarium avenaceum, Byssochlamys nivea and Aspergillus fumigatus have previously been identified as major fungal contaminants of Danish maize silage. In the present study their metabolite....... roqueforti metabolites roquefortine C (48μg/mL), andrastin A (>50μg/mL), mycophenolic acid (>100μg/mL) and 1-hydroxyeremophil-7(11),9(10)-dien-8-one (>280μg/mL) were high. Fractionating of agar extracts identified PR-toxin as an important cytotoxic P. roqueforti metabolite, also detectable in maize silage....... The strongly cytotoxic B. nivea and P. paneum agar extracts contained patulin above the IC50 of 0.6μg/mL, however inoculated onto maize silage B. nivea and P. paneum did not produce patulin (>371μg/kg). Still B. nivea infected maize silage containing mycophenolic acid (∼50mg/kg), byssochlamic acid and other...

  13. Inhibition of hepatic lipogenesis by 2-tetradecylglycidic acid.

    Science.gov (United States)

    McCune, S A; Nomura, T; Harris, R A

    1979-10-01

    2-Tetradecylglycidic acid (TDGA), a hypoglycemic agent, has been found to be a very effective inhibitor of de novo fatty acid synthesis by isolated hepatocytes. A comparison was made between the effectiveness of TDGA and 5-(tetradecyloxy)-2-furoic acid (TOFA), a hypolipidemic agent, on the metabolic processes of isolated hepatocytes. These compounds are structurally related and both inhibit fatty acid synthesis; however, they have opposite effects from each other on the oxidation and esterification of fatty acids. TDGA inhibits whereas TOFA stimulates fatty acid oxidation. TDGA stimulates whereas TOFA inhibits fatty acid esterification.

  14. Anti-Infectious Agents against MRSA

    Directory of Open Access Journals (Sweden)

    Nobuhiro Koyama

    2012-12-01

    Full Text Available Clinically useful antibiotics, β-lactams and vancomycin, are known to inhibit bacterial cell wall peptidoglycan synthesis. Methicillin-resistant Staphylococcus aureus (MRSA has a unique cell wall structure consisting of peptidoglycan and wall teichoic acid. In recent years, new anti-infectious agents (spirohexaline, tripropeptin C, DMPI, CDFI, cyslabdan, 1835F03, and BPH-652 targeting MRSA cell wall biosynthesis have been discovered using unique screening methods. These agents were found to inhibit important enzymes involved in cell wall biosynthesis such as undecaprenyl pyrophosphate (UPP synthase, FemA, flippase, or UPP phosphatase. In this review, the discovery, the mechanism of action, and the future of these anti-infectious agents are described.

  15. Renal function, efficacy, and safety of sirolimus and mycophenolate mofetil after short-term calcineurin inhibitor-based quadruple therapy in de novo renal transplant patients: one-year analysis of a randomized multicenter trial.

    Science.gov (United States)

    Guba, Markus; Pratschke, Johann; Hugo, Christian; Krämer, Bernhard K; Nohr-Westphal, Constanze; Brockmann, Jens; Andrassy, Joachim; Reinke, Petra; Pressmar, Katharina; Hakenberg, Oliver; Fischereder, Michael; Pascher, Andreas; Illner, Wolf-Dieter; Banas, Bernhard; Jauch, Karl-Walter

    2010-07-27

    De novo sirolimus in calcineurin inhibitor-free regimens, although potentially useful to improve early renal function, are complicated by various drug-related side effects. We report a prospective open-label, multicenter, randomized trial to evaluate early conversion from a CsA-based to a sirolimus (SRL)-based regimen 10 to 24 days after renal transplantation. Of the 196 patients, 141 patients with a low-to-moderate immunological risk were eligible to be converted to SRL or to continue CsA. All patients received antithymocyte globulin-F single-bolus induction, mycophenolate mofetil, and steroids. The primary endpoint, renal function determined by S-creatinine and estimated glomerular filtration rate calculated by Nankivell formula at 12 months was significantly better in the SRL group (1.51+/-0.59 vs. 1.87+/-0.98 mg/dL or 64.5+/-25.2 vs. 53.4+/-18.0 mL/min/1.73 m). Patient survival, graft survival, and incidence of biopsy-proven acute rejection after conversion were not statistically different. Drug discontinuations were significantly higher in the SRL group (36.2% vs. 19.7%). Significantly, more patients in the SRL group reported acne, aphtous, and temporary hyperlipidemia, whereas cytomegalovirus viremia was significantly decreased (7.3% vs. 28.2%). Early conversion to a calcineurin inhibitor-free regimen with SRL in combination with mycophenolate mofetil may be a useful strategy to improve renal function. The identification of appropriate candidates and safe management of SRL-related adverse events will be a key to avoid the high rate of dropouts, which currently limit the broad applicability of this protocol.

  16. Effects of dicarbonyl trapping agents, antioxidants, and reducing agents on the formation of furan and other volatile components in canned-coffee model systems.

    Science.gov (United States)

    Zheng, Li Wei; Chung, Hyun; Kim, Young-Suk

    2015-09-01

    The formation of furan and certain volatiles related to furan formation mechanisms was studied using gas chromatography-mass spectrometry combined with solid-phase micro extraction after adding dicarbonyl trapping agents [epicatechin (EC), epigallocatechin gallate (EGCG), and catechin], water-soluble antioxidants (Trolox, caffeic acid, ferulic acid, and chlorogenic acid), fat-soluble antioxidants (α-tocopherol, BHT, and β-carotene), and reducing agents (glutathione and sodium sulfite) to canned-coffee model systems (CMS). The level of furan formation decreased significantly following the addition of EC (by 65.3%), EGCG (by 60.0%), and catechin (by 44.7%). In addition, the formation of Maillard reaction products, including furan derivatives (furfural and 5-methylfurfural), Strecker aldehyde (2-methylbutanal), pyrazines (2,6-dimethylpyrazine), and lipid oxidation products (including hexanal and 2-pentylfuran) was suppressed when any of the dicarbonyl trapping agents was added. Among the water-soluble antioxidants studied, chlorogenic acid most significantly decreased the furan level, by 67.0%, followed by ferulic acid (57.6%), Trolox (50.1%), and caffeic acid (48.2%) in the CMS. Chlorogenic acid also reduced the formation of furfural and lipid oxidation products. However, the addition of caffeic acid, ferulic acid, and chlorogenic acid decreased the generation of key coffee aroma components, such as Strecker aldehydes (2-methylpropanal and 2-methylbutanal), 5-methylfurfural, and pyrazines (2,6-dimethylpyrazine and 2-ethyl-5-methylpyrazine). Among the fat-soluble antioxidants, BHT and α-tocopherol decreased the furan level by 49.3% and 39.3%, respectively, while β-carotene increased the furan level by 34.8%. The addition of sodium sulfite and glutathione to CMS also led to considerable reductions in furan, of 64.1% and 44.9%, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Specific sequestering agents for the actinides: Pt. 10

    International Nuclear Information System (INIS)

    Ren Hongyu; Wang Huicai

    1991-01-01

    In this article, ten new and four known polyaminocarboxy-licphenolic sequestering agents have been synthesized. The result of animal screening of ten of these sequestering agents indicates: six of all, at a dose of 50 μmol/kg can excrete liver Am·Va (N, N'-di(2-hydroxybenzyl)-diethylenetriamine-N 1 , N 4 , N 7 -triacetic acid) is the most effective, it can excrete liver Am, skeleten Am and kidney Am. But all are less effective than DTPA. The structure-activity relationship has been discussed, ligand with more aminocarboxylic acid groups showed a better result than the ligand with more phenolic groups

  18. Extracting metal ions with diphosphonic acid, or derivative thereof

    Science.gov (United States)

    Horwitz, Earl P.; Gatrone, Ralph C.; Nash, Kenneth L.

    1994-01-01

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulphur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described.

  19. Cytocompatibility and Mechanical Properties of Short Phosphate Glass Fibre Reinforced Polylactic Acid (PLA Composites: Effect of Coupling Agent Mediated Interface

    Directory of Open Access Journals (Sweden)

    Gavin Walker

    2012-10-01

    Full Text Available In this study three chemical agents Amino-propyl-triethoxy-silane (APS, sorbitol ended PLA oligomer (SPLA and Hexamethylene diisocyanate (HDI were identified to be used as coupling agents to react with the phosphate glass fibre (PGF reinforcement and the polylactic acid (PLA polymer matrix of the composite. Composites were prepared with short chopped strand fibres (l = 20 mm, ϕ = 20 µm in a random arrangement within PLA matrix. Improved, initial composite flexural strength (~20 MPa was observed for APS treated fibres, which was suggested to be due to enhanced bonding between the fibres and polymer matrix. Both APS and HDI treated fibres were suggested to be covalently linked with the PLA matrix. The hydrophobicity induced by these coupling agents (HDI, APS helped to resist hydrolysis of the interface and thus retained their mechanical properties for an extended period of time as compared to non-treated control. Approximately 70% of initial strength and 65% of initial modulus was retained by HDI treated fibre composites in contrast to the control, where only ~50% of strength and modulus was retained after 28 days of immersion in PBS at 37 °C. All coupling agent treated and control composites demonstrated good cytocompatibility which was comparable to the tissue culture polystyrene (TCP control, supporting the use of these materials as coupling agent’s within medical implant devices.

  20. Bond strength of compomers to dentin using acidic primers.

    Science.gov (United States)

    Tate, W H; You, C; Powers, J M

    1999-10-01

    To determine the in vitro bond strengths of seven compomer/bonding agent restorative systems to human dentin. Seven compomer/bonding agents were bonded to human dentin, stored in water at 37 degrees C for 24 hours, and debonded in tension. Bonding conditions were with and without phosphoric acid etching, with and without the use of combined primer/bonding agents, and under moist and wet bond interfaces. Without phosphoric acid etching, F2000/F2000 Compomer Primer/Adhesive and F2000/Single Bond Dental Adhesive System were less sensitive to dentin wetness. With moist dentin, bond strengths of Dyract/Prime & Bond 2.1, Dyract AP/Prime & Bond 2.1, Hytac/OSB light-curing, one-component bonding agent, F2000/Single Bond, and Freedom/STAE single component light-cured dentin/enamel adhesive system, were improved with phosphoric acid etching. Also, with moist dentin, the bond strength of F2000/F2000 Compomer Primer/Adhesive in the 3M Clicker dispensing system was higher without phosphoric acid etching, whereas bonds of Compoglass/Syntac Single-component were not affected by phosphoric acid etching. Bonding did not occur without primer/bonding agent, regardless of surface condition or use of phosphoric acid etching.

  1. The effect of nitrate, bicarbonate and natural organic matter on the degradation of sunscreen agent p-aminobenzoic acid by simulated solar irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Liang, E-mail: lmao@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Meng, Cui; Zeng, Chao; Ji, Yuefei [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); Yang, Xi, E-mail: yangxi@nju.edu.cn [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China); State Key Laboratory of Marine Environmental Science, Xiamen University, Xiamen 361005 (China); Gao, Shixiang [State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210093 (China)

    2011-11-15

    Our experiments revealed that a model sunscreen agent, p-aminobenzoic acid (PABA), can be effectively transformed through reactions that are mediated by simulated solar irradiation. We systematically explored the effects of nitrate ions, bicarbonate and different types of natural organic matter (NOM) on the degradation of PABA by simulated solar irradiation. Experimental data suggest that these components ubiquitous in nature water have different influence on the rates of the photoinduced removal of PABA. Products were extracted and analyzed using LC/MS and a total of four products probably resulting from {center_dot}OH and {center_dot}NO{sub 2} radicals attack were identified and the possible reaction pathways were proposed. The findings in this study provide useful information for understanding the environmental transformation of sunscreen agent in aquatic system. - Highlights: {yields} In this study, we found that p-aminobenzoic acid (PABA) can be removed by simulated solar irradiation from water. {yields} Influence of environmental components on the photodegradation of PABA was further studied. {yields} We verified using LC/MS that PABA was transformed into four compounds. {yields} We proposed the possible reaction pathways probably resulting from {center_dot}OH and {center_dot}NO{sub 2} radicals attack to PABA.

  2. The effect of nitrate, bicarbonate and natural organic matter on the degradation of sunscreen agent p-aminobenzoic acid by simulated solar irradiation

    International Nuclear Information System (INIS)

    Mao, Liang; Meng, Cui; Zeng, Chao; Ji, Yuefei; Yang, Xi; Gao, Shixiang

    2011-01-01

    Our experiments revealed that a model sunscreen agent, p-aminobenzoic acid (PABA), can be effectively transformed through reactions that are mediated by simulated solar irradiation. We systematically explored the effects of nitrate ions, bicarbonate and different types of natural organic matter (NOM) on the degradation of PABA by simulated solar irradiation. Experimental data suggest that these components ubiquitous in nature water have different influence on the rates of the photoinduced removal of PABA. Products were extracted and analyzed using LC/MS and a total of four products probably resulting from ·OH and ·NO 2 radicals attack were identified and the possible reaction pathways were proposed. The findings in this study provide useful information for understanding the environmental transformation of sunscreen agent in aquatic system. - Highlights: → In this study, we found that p-aminobenzoic acid (PABA) can be removed by simulated solar irradiation from water. → Influence of environmental components on the photodegradation of PABA was further studied. → We verified using LC/MS that PABA was transformed into four compounds. → We proposed the possible reaction pathways probably resulting from ·OH and ·NO 2 radicals attack to PABA.

  3. Evaluation of labelling conditions, quality control and biodistribution study of 99mTc-5-aminolevulinic acid (5-ALA). A potential liver imaging agent

    International Nuclear Information System (INIS)

    Kalim Ullah Khan; Mohammad Rafi; Samina Roohi; Rizwana Zahoor; Zafar Iqbal; Mushtaq Ahmad

    2014-01-01

    Labelling of 5-aminolevulinic acid (5-ALA) with 99m Tc was achieved by using SnCl 2 ·2H 2 O as reducing agent. Radiochemical purity and labelling efficiency was determined by instant thin layer chromatography/paper chromatography. Efficiency of labelling was dependent on many parameters such as amount of ligand, reducing agent, pH, and time of incubation. 99m Tc labelled 5-ALA remained stable for 24 h in human serum. Tissue biodistribution of 99m Tc-5-ALA was evaluated in Sprague-Dawley rats. Biodistribution study (% ID/g) in rats revealed that 99m Tc-5-ALA was accumulated significantly in liver, spleen, stomach and intestine after half hour, 4 and 24 h. Significant activity was noted in bladder and urine at 4 h. High liver uptake of 99m Tc-5-ALA makes it a promising liver imaging agent. (author)

  4. Extraction of americium from acid aqueous solutions by diethyl-2-hexyl-pyro-phosphoric acid

    International Nuclear Information System (INIS)

    Guillaume, Bernard

    1971-02-01

    After having outlined the interesting properties of americium and the difficulties of its recovery, the author reports the study of the mechanism of extraction of americium from acid aqueous solutions by using the diethyl-2hexyl-pyro-phosphoric acid. Several aspects are thus discussed: influence of concentration of H 2 DEHPP, influence of the acidity of the aqueous phase, saturation of extracting agent, influence of the diluting agent, complexing of americium, influence of other cations. In a second part, the author reports the application to the recovery of americium from effluents, and discusses the obtained results

  5. Poly(vinyl chloride) catheters modified with pH-responsive poly(methacrylic acid) with affinity for antimicrobial agents

    Science.gov (United States)

    Zuñiga-Zamorano, Ivette; Meléndez-Ortiz, H. Iván; Costoya, Alejandro; Alvarez-Lorenzo, Carmen; Concheiro, Angel; Bucio, Emilio

    2018-01-01

    Radiation-grafting of pH-responsive methacrylic acid (MAA) onto poly(vinyl chloride) (PVC) was carried out by the pre-irradiation method using gamma rays, which demonstrated to be an efficient and fast procedure for obtaining PVC-g-MAA copolymers. The influence of preparation conditions, such as absorbed dose, monomer concentration, reaction time, and reaction temperature on the grafting yield was studied. The grafting of MAA onto PVC catheters was confirmed by means of Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), and differential scanning calorimetry (DSC). The pH-responsiveness of the grafted copolymers (critical point 8.5) was measured by swelling under cyclic changes in the pH of the medium. Interestingly, PVC-g-MAA showed enhanced capability to immobilize benzalkonium chloride and, particularly, ciprofloxacin and to sustain the release this antimicrobial agent at both acid and alkaline pH. Tests carried out with Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus point out that the developed functionalized catheters may play a role in the prevention/management of urinary tract infections.

  6. Extracting metal ions with diphosphonic acid, or derivative thereof

    Science.gov (United States)

    Horwitz, E.P.; Gatrone, R.C.; Nash, K.L.

    1994-07-26

    Thermodynamically-unstable complexing agents which are diphosphonic acids and diphosphonic acid derivatives (or sulfur containing analogs), like carboxyhydroxymethanediphosphonic acid and vinylidene-1,1-diphosphonic acid, are capable of complexing with metal ions, and especially metal ions in the II, III, IV, V and VI oxidation states, to form stable, water-soluble metal ion complexes in moderately alkaline to highly-acidic media. However, the complexing agents can be decomposed, under mild conditions, into non-organic compounds which, for many purposes are environmentally-nondamaging compounds thereby degrading the complex and releasing the metal ion for disposal or recovery. Uses for such complexing agents as well as methods for their manufacture are also described. 1 fig.

  7. Evaluation of Ga-DOTA-(D-Asp)n as bone imaging agents: D-aspartic acid peptides as carriers to bone

    OpenAIRE

    Ogawa, Kazuma; Ishizaki, Atsushi; Takai, Kenichiro; Kitamura, Yoji; Makino, Akira; Kozaka, Takashi; Kiyono, Yasushi; Shiba, Kazuhiro; Odani, Akira

    2017-01-01

    67Ga-DOTA-(L-Asp)11 and 67Ga-DOTA-(L-Asp)14, which have been developed as bone imaging agents, showed a high accumulation in bone and a rapid blood clearance in mice. However, peptides composed of D-amino acids are more stable in vivo than those composed of their L-equivalents. In this study, 67Ga-DOTA-(D-Asp)n (n = 2, 5, 8, 11, or 14) were synthesized using the Fmoc-based solid-phase methodology and evaluated. In hydroxyapatite binding assay, binding of 67Ga-DOTA-(D-Asp)n tended to increase ...

  8. Folic acid tagged nanoceria as a novel therapeutic agent in ovarian cancer

    International Nuclear Information System (INIS)

    Hijaz, Miriana; Das, Soumen; Mert, Ismail; Gupta, Ankur; Al-Wahab, Zaid; Tebbe, Calvin; Dar, Sajad; Chhina, Jasdeep; Giri, Shailendra; Munkarah, Adnan; Seal, Sudipta; Rattan, Ramandeep

    2016-01-01

    Nanomedicine is a very promising field and nanomedical drugs have recently been used as therapeutic agents against cancer. In a previous study, we showed that Nanoceria (NCe), nanoparticles of cerium oxide, significantly inhibited production of reactive oxygen species, cell migration and invasion of ovarian cancer cells in vitro, without affecting cell proliferation and significantly reduced tumor growth in an ovarian cancer xenograft nude model. Increased expression of folate receptor-α, an isoform of membrane-bound folate receptors, has been described in ovarian cancer. To enable NCe to specifically target ovarian cancer cells, we conjugated nanoceria to folic acid (NCe-FA). Our aim was to investigate the pre-clinical efficacy of NCe-FA alone and in combination with Cisplatin. Ovarian cancer cell lines were treated with NCe or NCe-FA. Cell viability was assessed by MTT and colony forming units. In vivo studies were carried in A2780 generated mouse xenografts treated with 0.1 mg/Kg NCe, 0.1 mg/Kg; NCe-FA and cisplatinum, 4 mg/Kg by intra-peritoneal injections. Tumor weights and burden scores were determined. Immunohistochemistry and toxicity assays were used to evaluate treatment effects. We show that folic acid conjugation of NCe increased the cellular NCe internalization and inhibited cell proliferation. Mice treated with NCe-FA had a lower tumor burden compared to NCe, without any vital organ toxicity. Combination of NCe-FA with cisplatinum decreased the tumor burden more significantly. Moreover, NCe-FA was also effective in reducing proliferation and angiogenesis in the xenograft mouse model. Thus, specific targeting of ovarian cancer cells by NCe-FA holds great potential as an effective therapeutic alone or in combination with standard chemotherapy. The online version of this article (doi:10.1186/s12885-016-2206-4) contains supplementary material, which is available to authorized users

  9. 9 CFR 121.3 - VS select agents and toxins.

    Science.gov (United States)

    2010-01-01

    ... genetically modified. (d) VS select agents or toxins that meet any of the following criteria are excluded from... AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE, AND... recombinant organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent viruses...

  10. 9 CFR 121.4 - Overlap select agents and toxins.

    Science.gov (United States)

    2010-01-01

    ... in paragraph (b) of this section that have been genetically modified. (d) Overlap select agents or... OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS POSSESSION, USE... elements, recombinant nucleic acids, and recombinant organisms: (1) Nucleic acids that can produce...

  11. Phenolic aminocarboxylic acids - new chelating agents for modifying gallium-67 biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, F.C.; Maddalena, D.J. (Australian Atomic Energy Commission Research Establishment, Lucas Heights)

    The chelating agents EDDHA and HBED were synthesised with carboxyl or sulphonyl groups in the phenolic ring to favour urinary excretion on complexing with gallium. Carboxyl EDDMA was administered to tumor-bearing rats, and its concentration in the tumours and other tissues determined by scintigraphic imaging. The chelating agents increase tumour to blood ratios by chelating gallium in vivo.

  12. Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid

    Energy Technology Data Exchange (ETDEWEB)

    Barahuie, Farahnaz [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Zabol University of Medical Sciences, Zabol (Iran, Islamic Republic of); Saifullah, Bullo [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Dorniani, Dena [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Chemistry Department, University of Sheffield, Dainton Building, Brook Hill, Sheffield S3 7HF (United Kingdom); Fakurazi, Sharida [Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Karthivashan, Govindarajan [Laboratory of Vaccines and Immunotherapeutics, Institute of Bioscience, Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Hussein, Mohd Zobir, E-mail: mzobir@upm.edu.my [Materials Synthesis and Characterization Laboratory, Institute of Advanced Technology (ITMA), Universiti Putra Malaysia UPM, 43400 Serdang, Selangor (Malaysia); Elfghi, Fawzi M. [Department of Chemical and Petrochemical Engineering, The College of Engineering & Architecture, Initial Campus, Birkat Al Mouz Nizwa (Oman)

    2017-05-01

    We have synthesized graphene oxide using improved Hummer's method in order to explore the potential use of the resulting graphene oxide as a nanocarrier for an active anticancer agent, chlorogenic acid (CA). The synthesized graphene oxide and chlorogenic acid-graphene oxide nanocomposite (CAGO) were characterized using Fourier transform infrared (FTIR) spectroscopy, thermogravimetry and differential thermogravimetry analysis, Raman spectroscopy, powder X-ray diffraction (PXRD), UV–vis spectroscopy and high resolution transmission electron microscopy (HRTEM) techniques. The successful conjugation of chlorogenic acid onto graphene oxide through hydrogen bonding and π–π interaction was confirmed by Raman spectroscopy, FTIR analysis and X-ray diffraction patterns. The loading of CA in the nanohybrid was estimated to be around 13.1% by UV–vis spectroscopy. The release profiles showed favourable, sustained and pH-dependent release of CA from CAGO nanocomposite and conformed well to the pseudo-second order kinetic model. Furthermore, the designed anticancer nanohybrid was thermally more stable than its counterpart. The in vitro cytotoxicity results revealed insignificant toxicity effect towards normal cell line, with a viability of > 80% even at higher concentration of 50 μg/mL. Contrarily, CAGO nanocomposite revealed enhanced toxic effect towards evaluated cancer cell lines (HepG2 human liver hepatocellular carcinoma cell line, A549 human lung adenocarcinoma epithelial cell line, and HeLa human cervical cancer cell line) compared to its free form. - Highlights: • Graphene oxide is synthesized using improved Hummer's method • The suppression of cancer cell growth was higher for chlorogenic acid/graphene oxide nanocomposite than for pure chlorogenic acid • Chlorogenic acid/graphene oxide nanocomposite has the potential to be used as a sustained release formulation.

  13. Bioprospecting the Curculigoside-Cinnamic Acid-Rich Fraction from Molineria latifolia Rhizome as a Potential Antioxidant Therapeutic Agent

    Directory of Open Access Journals (Sweden)

    Der Jiun Ooi

    2016-06-01

    Full Text Available Increasing evidence from both experimental and clinical studies depicts the involvement of oxidative stress in the pathogenesis of various diseases. Specifically, disruption of homeostatic redox balance in accumulated body fat mass leads to obesity-associated metabolic syndrome. Strategies for the restoration of redox balance, potentially by exploring potent plant bioactives, have thus become the focus of therapeutic intervention. The present study aimed to bioprospect the potential use of the curculigoside-cinnamic acid-rich fraction from Molineria latifolia rhizome as an antioxidant therapeutic agent. The ethyl acetate fraction (EAF isolated from M. latifolia rhizome methanolic extract (RME contained the highest amount of phenolic compounds, particularly curculigoside and cinnamic acid. EAF demonstrated glycation inhibitory activities in both glucose- and fructose-mediated glycation models. In addition, in vitro chemical-based and cellular-based antioxidant assays showed that EAF exhibited high antioxidant activities and a protective effect against oxidative damage in 3T3-L1 preadipocytes. Although the efficacies of individual phenolics differed depending on the structure and concentration, a correlational study revealed strong correlations between total phenolic contents and antioxidant capacities. The results concluded that enriched phenolic contents in EAF (curculigoside-cinnamic acid-rich fraction contributed to the overall better reactivity. Our data suggest that this bioactive-rich fraction warrants therapeutic potential against oxidative stress-related disorders.

  14. In Vitro Dissolution of Fluconazole and Dipyridamole in Gastrointestinal Simulator (GIS), Predicting in Vivo Dissolution and Drug-Drug Interaction Caused by Acid-Reducing Agents.

    Science.gov (United States)

    Matsui, Kazuki; Tsume, Yasuhiro; Amidon, Gregory E; Amidon, Gordon L

    2015-07-06

    Weakly basic drugs typically exhibit pH-dependent solubility in the physiological pH range, displaying supersaturation or precipitation along the gastrointestinal tract. Additionally, their oral bioavailabilities may be affected by coadministration of acid-reducing agents that elevate gastric pH. The purpose of this study was to assess the feasibility of a multicompartmental in vitro dissolution apparatus, Gastrointestinal Simulator (GIS), in predicting in vivo dissolution of certain oral medications. In vitro dissolution studies of fluconazole, a BCS class I, and dipyridamole, a BCS class II weak bases (class IIb), were performed in the GIS as well as United States Pharmacopeia (USP) apparatus II and compared with the results of clinical drug-drug interaction (DDI) studies. In both USP apparatus II and GIS, fluconazole completely dissolved within 60 min regardless of pH, reflecting no DDI between fluconazole and acid-reducing agents in a clinical study. On the other hand, seven-fold and 15-fold higher concentrations of dipyridamole than saturation solubility were observed in the intestinal compartments in GIS with gastric pH 2.0. Precipitation of dipyridamole was also observed in the GIS, and the percentage of dipyridamole in solution was 45.2 ± 7.0%. In GIS with gastric pH 6.0, mimicking the coadministration of acid-reducing agents, the concentration of dipyridamole was equal to its saturation solubility, and the percentage of drug in solution was 9.3 ± 2.7%. These results are consistent with the clinical DDI study of dipyridamole with famotidine, which significantly reduced the Cmax and area under the curve. An In situ mouse infusion study combined with GIS revealed that high concentration of dipyridamole in the GIS enhanced oral drug absorption, which confirmed the supersaturation of dipyridamole. In conclusion, GIS was shown to be a useful apparatus to predict in vivo dissolution for BCS class IIb drugs.

  15. Assimilate unloading from maize (Zea mays L.) pedicel tissues. II. Effects of chemical agents on sugar, amino acid, and 14C-assimilate unloading

    International Nuclear Information System (INIS)

    Porter, G.A.; Knievel, D.P.; Shannon, J.C.

    1987-01-01

    Sugar, amino acid, and 14 C-assimilate release from attached maize (Zea mays L.) pedicels was studied following treatment with several chemical inhibitors. In the absence of these agents, sugar release was nearly linear over a 7-hour period. At least 13 amino acids were released with glutamine comprising over 30% of the total. Release was not affected by potassium concentration, 10-minute pretreatments with p-chloromercuribenzene sulfonic acid (PCMBS) or dithiothreitol, and low concentrations of CaCl 2 . Three hours or more exposure to PCMBS, dinitrophenol, N-ethylmaleimide, or 2,4,6-trinitrobenzene sulfonic acid strongly inhibited 14 C-assimilate, sugar, and amino acid release from the pedicel. These treatments also reduced 14 C-assimilate movement into the kernel bases. It is, therefore, likely that reduced unloading, caused by these relatively long-term exposures to chemical inhibitors, was related to reduced translocation of assimilates into treated kernels. Whether this effect is due to disruption of kernel metabolism and sieve element function or reduced assimilate unloading and subsequent accumulation of unlabeled assimilates within the pedicel tissues cannot be determined at this time

  16. Phenolic aminocarboxylic acids - new chelating agents for modifying gallium-67 biodistribution

    International Nuclear Information System (INIS)

    Hunt, F.C.; Maddalena, D.J.

    1982-01-01

    The chelating agents EDDHA and HBED were synthesised with carboxyl or sulphonyl groups in the phenolic ring to favour urinary excretion on complexing with gallium. Carboxyl EDDMA was administered to tumor-bearing rats, and its concentration in the tumours and other tissues determined by scintigraphic imaging. The chelating agents increase tumour to blood ratios by chelating gallium in vivo. (U.K.)

  17. New method for studying the efficiency of chelating agents of the polyamine acid series for internal decontamination; Methode nouvelle d'etude de l'efficacite des chelateurs de la serie des acides polyamines pour la decontamination interne

    Energy Technology Data Exchange (ETDEWEB)

    Lafuma, J; Nenot, J C; Morin, M [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1968-07-01

    We followed the biological fate of a complex formed on one side with either a rare earth (cerium-144) or a transuranium element (plutonium-239), and on the other side with a chelating agent of the polyamino acid series (EDTA, BAETA, DTPA, TTHA). This method allowed to study: 1 - the in vivo stability of the various complexes and to compare them; 2 - the stability of the complexes as a function of the isotope - chelating agent weight relationships; 3 - the metabolism of the chelating agents resulting in stable complexes, i. e. DTPA and TTHA mainly. This simple method brought out the higher efficiency, of DTPA in chelating rare earths and plutonium and for therapeutic purposes. (authors) [French] La methode consiste a suivre le devenir biologique d'un complexe forme d'une part avec une terre rare (cerium 144) ou un transuranien (plutonium 239) et d'autre part avec un chelateur de la serie des acides polyamines (EDTA, BAETA, DTPA, TTHA). Elle permet d'etudier: 1 - la stabilite in vivo des differents complexes, de les comparer; 2 - la stabilite des complexes en fonction des rapports ponderaux isotope - chelateurs; 3 - le metabolisme des chelateurs formant des complexes stables, essentiellement DTPA et TTHA. Cette methode simple degage la suprematie du DTPA en ce qui concerne la chelation des terres rares et du plutonium, et son utilisation a des fins therapeutiques. (auteurs)

  18. Synthesis and evaluation of novel bifunctional chelating agents based on 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid for radiolabeling proteins

    International Nuclear Information System (INIS)

    Chappell, L.L.; Ma, D.; Milenic, D.E.; Garmestani, K.; Venditto, V.; Beitzel, M.P.; Brechbiel, M.W.

    2003-01-01

    Detailed synthesis of the bifunctional chelating agents 2-methyl-6-(p-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10 -tetraacetic acid (1B4M-DOTA) and 2-(p-isothiocyanatobenzyl)-5, 6-cyclohexano-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate (CHX-DOTA) are reported. These chelating agents were compared to 2-(p-isothiocyanatobenzyl)-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (C-DOTA) and 1, 4, 7, 10-Tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N', N'', N'''-tris(acetic acid) cyclododecane (PA-DOTA) as their 177 Lu radiolabeled conjugates with Herceptin TM . In vitro stability of the immunoconjugates radiolabeled with 177 Lu was assessed by serum stability studies. The in vivo stability of the radiolabeled immunoconjugates and their targeting characteristics were determined by biodistribution studies in LS-174T xenograft tumor-bearing mice. Relative radiolabeling rates and efficiencies were determined for all four immunoconjugates. Insertion of the 1B4M moiety into the DOTA backbone increases radiometal chelation rate and provides complex stability comparable to C-DOTA and PA-DOTA while the CHX-DOTA appears to not form as stable a 177 Lu complex while exhibiting a substantial increase in formation rate. The 1B4M-DOTAmay have potential for radioimmunotherapy applications. Published by Elsevier Inc. All rights reserved

  19. Use of tetracycline as complexing agent in analytical chemistry

    International Nuclear Information System (INIS)

    Nastasi, M.J.C.; Saiki, M.; Lima, F.W.

    1977-01-01

    The behavior of tetracyline as complexing agent in solvent extraction studies is presented. The extraction curves for the lanthanide elements, scandium, thorium, uranium and neptunium, are determined for the extraction system benzyl alcohol-tetracycline, as well as the acid and extractant dependences of extraction of the lanthanide elements. Separation of neptunium from uranium is formed by carrying out the extraction experiment at a proper pH value. Use is made of masking agents namely, ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA), in order to obtain separations of uranium from scadium and lanthanides as well as of uranium and thorium, respectively. The extraction experiments are carried out by using radioisotopes of each element, except for uranium in which case the determinations are by using epithermal neutron activation analysis [pt

  20. Effect of poly-α, γ, L-glutamic acid as a capping agent on morphology and oxidative stress-dependent toxicity of silver nanoparticles

    Science.gov (United States)

    Stevanović, Magdalena; Kovačević, Branimir; Petković, Jana; Filipič, Metka; Uskoković, Dragan

    2011-01-01

    Highly stable dispersions of nanosized silver particles were synthesized using a straightforward, cost-effective, and ecofriendly method. Nontoxic glucose was utilized as a reducing agent and poly-α, γ, L-glutamic acid (PGA), a naturally occurring anionic polymer, was used as a capping agent to protect the silver nanoparticles from agglomeration and render them biocompatible. Use of ammonia during synthesis was avoided. Our study clearly demonstrates how the concentration of the capping agent plays a major role in determining the dimensions, morphology, and stability, as well as toxicity of a silver colloidal solution. Hence, proper optimization is necessary to develop silver colloids of narrow size distribution. The samples were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and zeta potential measurement. MTT assay results indicated good biocompatibility of the PGA-capped silver nanoparticles. Formation of intracellular reactive oxygen species was measured spectrophotometrically using 2,7-dichlorofluorescein diacetate as a fluorescent probe, and it was shown that the PGA-capped silver nanoparticles did not induce intracellular formation of reactive oxygen species. PMID:22131829

  1. Synthesis of omega-hydroxy carboxylic acids and alpha,omega-dimethyl ketones using alpha,omega-diols as alkylating agents.

    Science.gov (United States)

    Iuchi, Yosuke; Hyotanishi, Megumi; Miller, Brittany E; Maeda, Kensaku; Obora, Yasushi; Ishii, Yasutaka

    2010-03-05

    Synthesis of omega-hydroxy carboxylic acids and alpha,omega-dimethyl diketones was successfully achieved by using alpha,omega-diols as alkylating agents under the influence of an iridium catalyst. For example, the alkylation of butyl cyanoacetate with 1,13-tridecanediol in the presence of [IrCl(cod)](2) or [IrCl(coe)(2)](2) gave rise to butyl 2-cyano-15-hydroxypentadecanoate in good yield which is easily converted to cyclopentadecanolide (CPDL). In addition, the alkylation of acetone with 1,10-decanediol in the presence of [IrCl(cod)](2) and KOH resulted in an important muscone precursor, 2,15-hexadecanedione (HDDO), in good yield.

  2. The preparation of solid acid and acid water reducing agent for slag is prepared by adsorption method

    Science.gov (United States)

    Zhao, Su; Wang, Jinpeng; Zhu, Xitong

    2018-03-01

    Solid polycarboxylate superplasticizer can not only solve the problems caused by water reducing agent in storage and transportation, but also meet the needs of some special projects. We can choose to use the mineral slag, which is larger than surface area and has stronger adsorption, as adsorbent to absorb liquid polycarboxylate superplasticizer and absorb its moisture, and then makes solid polycarboxylate superplasticizer after drying. It determines the solid-liquid ratio to prepare the solid polycarboxylate superplasticizer to be 3:1. The temperature change within 100°C will not cause changes in the functional group and structure of the water reducing agent molecule. The application of the solid polycarboxylate superplasticizer was basically unchanged compared with its liquid water reducing agent.

  3. Bile Acid Metabolism and Signaling

    Science.gov (United States)

    Chiang, John Y. L.

    2015-01-01

    Bile acids are important physiological agents for intestinal nutrient absorption and biliary secretion of lipids, toxic metabolites, and xenobiotics. Bile acids also are signaling molecules and metabolic regulators that activate nuclear receptors and G protein-coupled receptor (GPCR) signaling to regulate hepatic lipid, glucose, and energy homeostasis and maintain metabolic homeostasis. Conversion of cholesterol to bile acids is critical for maintaining cholesterol homeostasis and preventing accumulation of cholesterol, triglycerides, and toxic metabolites, and injury in the liver and other organs. Enterohepatic circulation of bile acids from the liver to intestine and back to the liver plays a central role in nutrient absorption and distribution, and metabolic regulation and homeostasis. This physiological process is regulated by a complex membrane transport system in the liver and intestine regulated by nuclear receptors. Toxic bile acids may cause inflammation, apoptosis, and cell death. On the other hand, bile acid-activated nuclear and GPCR signaling protects against inflammation in liver, intestine, and macrophages. Disorders in bile acid metabolism cause cholestatic liver diseases, dyslipidemia, fatty liver diseases, cardiovascular diseases, and diabetes. Bile acids, bile acid derivatives, and bile acid sequestrants are therapeutic agents for treating chronic liver diseases, obesity, and diabetes in humans. PMID:23897684

  4. Dynamic-contrast-enhanced magnetic resonance imaging of cirrhotic liver parenchyma: A comparison between gadolinium–diethylenetriamine pentaacetic acid and gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid

    OpenAIRE

    Lin, Chun-Yi; Chang, Wei-Chou; Chou, Chen-Te; Chen, Ran-Chou

    2015-01-01

    Background: The newly developed magnetic-resonance-imaging (MRI) hepatocyte-specific contrast agent, gadolinium–ethoxybenzyl–diethylenetriamine pentaacetic acid (Gd–EOB–DTPA), has different excretion pathways from the conventional MRI contrast agent, gadolinium–diethylenetriamine pentaacetic acid (Gd–DTPA). In this study, we compare the enhancement effect of the liver and renal parenchyma between these two contrast agents for patients with liver cirrhosis. Methods: We retrospectively inclu...

  5. [Interference for Various Quench Agents of Chemical Disinfectants on Detection of Endotoxin Activities in Water].

    Science.gov (United States)

    Zhang, Can; Liu, Wen-jun; Shi, Yun; An, Dai-zhi; Bai, Miao; Xu, Wen

    2015-05-01

    The quenching agents such as histidine, glycine, ascorbic acid, Tween-80, sodium sulfite and sodium hyposulfite are commonly used for quenching the residual disinfectant in water. In this paper, in order to select the optimal type and concentration range of quenching agents prior to the Limulus assays, the interference effects of each quenching agent at different concentrations on endotoxin detection were investigated by the Limulus assays of kinetic-turbidity. Our results identified that, as for 0-1.0% concentration of histidine, ascorbic acid, Tween-80, sodium sulfite (pH unadjusted and pH neutral), interference on the Limulus assays was existed. Hence, these quenching agents could not be applied as neutralizers prior to Limulus assays. Although, there was no interference on endotoxin detection for the glycine, a yellow color, developed by the quenching products of glycine and glutaric dialdehyde, contributed to false positive results. Hence, glycine should not be used as quenching agents in Limulus assays for samples containing glutaric dialdehyde. Compared with other quenching agents as histidine, glycine, ascorbic acid, Tween-80, sodium sulfite, 0-1.0% concentration of sodium hyposulfite elicited no obvious interference, while 1.0%-5.0% concentration of sodium hyposulfite illustrated exhibition effect for endotoxin detection. All in all, compared with other quenching agents as histidine, glycine, ascorbic acid, Tween-80 and sodium sulfite, sodium hyposulfite is suitable for quenching chemicals prior to endotoxin detection and less than 0.5% of concentration is allowable.

  6. A STUDY OF ANTIMICROBIAL ACTIVITY OF FOAM-WASHING AGENT SPECIMENS AT ACIDIC pH VALUES

    Directory of Open Access Journals (Sweden)

    Strilets O. P.

    2017-06-01

    Full Text Available Introduction. It is well-known that any parapharmaceutical substance, in particular, foam-washing agents comprising water in combination with detergents, extracts, water-soluble vitamins, viscosity regulators, pH, etc., is the ideal environment for microbial growth. Therefore, it is indispensable to use preservatives to protect any foam-washing agent from possible contamination by microorganisms. Their main advantages are: presence of a single antimicrobial and antifungal effect, expanded range of effects, decrease in the risk of resistance of microorganisms and decrease in the toxicity and concentration of the preserving mixture. In this regard, the shelf life of parapharmaceutical substances is not provided through the use of large quantities of preservatives, but thanks to their rational combination. Materials and Methods. For this study, we have made a number of samples of foam washing bases with a number of preservatives, which are often used in developing foam-washing agents with acidic pH value, namely: sample number 1 – foam washing base + sodium benzoate; sample number 2 – foam washing base + «Euxyl K300» (phenoxyethanol, methylparaben, bulylparaben, ethylparaben, propylparaben, isobutylaraben; sample number 3 – foam washing base + «Germaben II» (polypropylene glycol, diazolium dinomovine, methylparaben, propylparaben; sample number 4 – foam washing base + «Nipaquard CMB» (benzyl alcohol, triethylene glycol, chloromethylisothiazoline, methylisothiazoline. The concentration of preservative in each sample was 0.1% (average concentration that is recommended for developing foam-washing agents. The antimicrobial activity of prototype gels was studied in vitro by diffusion in agar (“wells” method. The antimicrobial activity was measured immediately after sample preparation. All the studies were performed in aseptic conditions using a laminar box (biological safety cabinet AS2-4E1 "Esco" Indonesia. Results. According to the

  7. Development of radioiodinated fatty acids for applications in nuclear cardiology

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.; Goodman, M.M.; Elmaleh, D.R.; Okada, R.; Strauss, H.W.

    1985-01-01

    The use of radioiodinated fatty acids for the evaluation of myocardial perfusion and the assessment of regional fatty acid metabolism in relation to myocardial disease have seen rapid growth in the last few years. In this paper the development and use of these agents are reviewed. In addition to a discussion of the design of structurally modified fatty acids, the development of new radiolabeling methods for preparation of the iodine-123-labeled agents is presented. The development of these new agents is discussed, and their potential use in conjunction with single-photon tomography is an exciting new area. A summary of the clinical studies involving measurement of regional washout rate which have been performed with agents such as 17-([ 123 I]iodo)heptadecanoic acid and 15-(p-[ 123 I]iodo phenyl)pentadecanoic acid is also presented. The combined interest and expertise of chemists and clinicians have worked effectively together to make many recent contributions to this area of radiopharmaceutical development

  8. Development of novel radiogallium-labeled bone imaging agents using oligo-aspartic acid peptides as carriers.

    Directory of Open Access Journals (Sweden)

    Kazuma Ogawa

    Full Text Available (68Ga (T 1/2 = 68 min, a generator-produced nuclide has great potential as a radionuclide for clinical positron emission tomography (PET. Because poly-glutamic and poly-aspartic acids have high affinity for hydroxyapatite, to develop new bone targeting (68Ga-labeled bone imaging agents for PET, we used 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA as a chelating site and conjugated aspartic acid peptides of varying lengths. Subsequently, we compared Ga complexes, Ga-DOTA-(Aspn (n = 2, 5, 8, 11, or 14 with easy-to-handle (67Ga, with the previously described (67Ga-DOTA complex conjugated bisphosphonate, (67Ga-DOTA-Bn-SCN-HBP. After synthesizing DOTA-(Aspn by a Fmoc-based solid-phase method, complexes were formed with (67Ga, resulting in (67Ga-DOTA-(Aspn with a radiochemical purity of over 95% after HPLC purification. In hydroxyapatite binding assays, the binding rate of (67Ga-DOTA-(Aspn increased with the increase in the length of the conjugated aspartate peptide. Moreover, in biodistribution experiments, (67Ga-DOTA-(Asp8, (67Ga-DOTA-(Asp11, and (67Ga-DOTA-(Asp14 showed high accumulation in bone (10.5 ± 1.5, 15.1 ± 2.6, and 12.8 ± 1.7% ID/g, respectively but were barely observed in other tissues at 60 min after injection. Although bone accumulation of (67Ga-DOTA-(Aspn was lower than that of (67Ga-DOTA-Bn-SCN-HBP, blood clearance of (67Ga-DOTA-(Aspn was more rapid. Accordingly, the bone/blood ratios of (67Ga-DOTA-(Asp11 and (67Ga-DOTA-(Asp14 were comparable with those of (67Ga-DOTA-Bn-SCN-HBP. In conclusion, these data provide useful insights into the drug design of (68Ga-PET tracers for the diagnosis of bone disorders, such as bone metastases.

  9. In-situ methylation of strongly polar organic acids in natural waters supported by ion-pairing agents for headspace GC-MSD analysis

    Energy Technology Data Exchange (ETDEWEB)

    Neitzel, P.L.; Walther, W. [Dresden University of Technology, Institute for Groundwater Managemant, Dresden (Germany); Nestler, W. [Institute for Technology and Economics, Department of Civil Engineering and Architecture, Dresden (Germany)

    1998-06-01

    Strongly polar organic substances like halogenated acetic acids have been analyzed in surface water and groundwater in the catchment area of the upper Elbe river in Saxony since 1992. Coming directly from anthropogenic sources like industry, agriculture and indirectly by rainfall, their concentrations can increase up to 100 {mu}g/L in the aquatic environment of this catchment area. A new static headspace GC-MSD method without a manual pre-concentration step is presented to analyze the chlorinated acetic acids relevant to the Elbe river as their volatile methyl esters. Using an ion-pairing agent as modifier for the in-situ methylation of the analytes by dimethylsulfate, a minimal detection limit of 1 {mu}g/L can be achieved. Problems like the thermal degradation of chlorinated acetic acids to halogenated hydrocarbons and changing reaction yields during the headspace methylation, could be effectively reduced. The method has been successfully applied to monitoring bank infiltrate, surface water, groundwater and water works pumped raw water according to health provision principles. (orig.) With 3 figs., 2 tabs., 29 refs.

  10. Synthesis of derivatives of tetronic acid and pulvinic acid. Total synthesis of norbadione A

    International Nuclear Information System (INIS)

    Mallinger, A.

    2008-11-01

    When vegetables like mushrooms are contaminated by radioactive caesium 137, this radioactive caesium is associated to norbadione A, a natural pigment present in two mushroom species and which can be used as a caesium decorporation agent or maybe as protection agent against ionizing radiations. Within this perspective, this research report describes the biosynthesis and the structure and properties of the norbadione A and of pulvinic acids (physicochemical properties, anti-oxidizing properties). Then, it presents the various tetronic acids (3-acyl-, 3-alkyl-, 3-alkoxy-, 3-aryl-tetronic acids and non 3-substituted tetronic acids), their synthesis path as they are described in the literature, and presents a new synthesis approach using a tandem reaction (with different esters or hydroxy esters) and the synthesis of tetronic acids. The author also proposes a new synthesis way for methyl pulvinates, and finally reports the work on the development of a total synthesis of the norbadione A

  11. Aqueous citric acid as a promising cleaning agent of whey evaporators

    DEFF Research Database (Denmark)

    Hedegaard, Martina Vavrusova; P. Johansen, Nikolaj; Garcia, André Castilho

    2017-01-01

    concentration of citric acid was the most effective for all the investigated volumes. From the citric acid solutions, spontaneously supersaturated in calcium citrate tetrahydrate during scale dissolution in the smaller volumes for all citric acid concentrations, calcium citrate tetrahydrate slowly precipitated...... in acceptable purity for technical use. Dissolution efficiency of aqueous solutions of 0.200 mol L−1 nitric acid combined with 0.100, 0.500, and 1.00 mol L−1 citric acid with final volumes of 100, 50, and 25 mL showed synergistic effect especially for the higher concentrations and lower volumes of two acids...

  12. New method for studying the efficiency of chelating agents of the polyamine acid series for internal decontamination; Methode nouvelle d'etude de l'efficacite des chelateurs de la serie des acides polyamines pour la decontamination interne

    Energy Technology Data Exchange (ETDEWEB)

    Lafuma, J.; Nenot, J.C.; Morin, M. [Commissariat a l' Energie Atomique, Fontenay-aux-Roses (France). Centre d' Etudes Nucleaires

    1968-07-01

    We followed the biological fate of a complex formed on one side with either a rare earth (cerium-144) or a transuranium element (plutonium-239), and on the other side with a chelating agent of the polyamino acid series (EDTA, BAETA, DTPA, TTHA). This method allowed to study: 1 - the in vivo stability of the various complexes and to compare them; 2 - the stability of the complexes as a function of the isotope - chelating agent weight relationships; 3 - the metabolism of the chelating agents resulting in stable complexes, i. e. DTPA and TTHA mainly. This simple method brought out the higher efficiency, of DTPA in chelating rare earths and plutonium and for therapeutic purposes. (authors) [French] La methode consiste a suivre le devenir biologique d'un complexe forme d'une part avec une terre rare (cerium 144) ou un transuranien (plutonium 239) et d'autre part avec un chelateur de la serie des acides polyamines (EDTA, BAETA, DTPA, TTHA). Elle permet d'etudier: 1 - la stabilite in vivo des differents complexes, de les comparer; 2 - la stabilite des complexes en fonction des rapports ponderaux isotope - chelateurs; 3 - le metabolisme des chelateurs formant des complexes stables, essentiellement DTPA et TTHA. Cette methode simple degage la suprematie du DTPA en ce qui concerne la chelation des terres rares et du plutonium, et son utilisation a des fins therapeutiques. (auteurs)

  13. Effect of Antiviral Agents in Equine Abortion Virus-Infected Hamsters1

    Science.gov (United States)

    Lieberman, Melvin; Pascale, Andrea; Schafer, Thomas W.; Came, Paul E.

    1972-01-01

    Equine abortion virus, a member of the herpesvirus group, produces a lethal infection in hamsters. With this system, the protective effect of certain inhibitors of deoxyribonucleic acid viruses, inducers of interferon and exogenous interferon, was evaluated. Of the various agents studied, 9-β-d-arabinofuranosyladenine markedly suppressed mortality, and 5-iodo-2′-deoxyuridine, distamycin A, and N-ethylisatin β-thiosemicarbazone were inactive. Of the inducers tested, statolon, ultraviolet-irradiated Newcastle disease virus, and polyriboinosinic:polyribocytidylic acid (poly I:C) were protective, and endotoxin, polyacrylic acid, and polymethacrylic acid did not protect. Administration of exogenous interferon did not afford protection. Statolon and ultraviolet-irradiated Newcastle disease virus induced circulating interferon in hamsters, whereas poly I:C, endotoxin, and polyacrylic acid did not produce interferon. Because of the severity of the disease produced in hamsters by equine abortion virus, lack of protective activity by an agent in this system should not preclude possible efficacy against other members of the herpesvirus group. PMID:4376907

  14. Synthesis of TiO(2)-PMMA nanocomposite: using methacrylic acid as a coupling agent.

    Science.gov (United States)

    Khaled, S M; Sui, Ruohong; Charpentier, Paul A; Rizkalla, Amin S

    2007-03-27

    Inorganic-polymer nanocomposites are of significant interest for emerging materials due to their improved properties and unique combination of properties. Methacrylic acid (MA), a functionalization agent that can chemically link TiO2 nanomaterials (n-TiO2) and polymer matrix, was used to modify the surface of n-TiO2 using a Ti-carboxylic coordination bond. Then, the double bond in MA was copolymerized with methyl methacrylate (MMA) to form a n-TiO2-PMMA nanocomposite. The resulting n-TiO2-PMMA nanocomposite materials were characterized by using thermal analysis, electron microscopy, and elemental analysis. The dynamic mechanical properties (Young's and shear modulus) were measured using an ultrasonic pulse technique. The electron microscopy results showed a good distribution of the nanofillers in the polymer matrix. The glass transition temperature, thermal degradation temperature, and dynamic elastic moduli of the nanocomposites were shown to increase with an increase in the weight percentage of nanofibers in the composite. The resulting nanocomposites exhibited improved elastic properties and have potential application in dental composites and bone cements.

  15. Evaluation of the metabolism in rat hearts of two new radioiodinated 3-methyl-branched fatty acid myocardial imaging agents

    Energy Technology Data Exchange (ETDEWEB)

    Ambrose, K R; Owen, B A; Goodman, M M; Knapp, Jr, F F

    1987-01-01

    The biological fate of two new radioiodinated 3-methyl-branched fatty acids has been evaluated in rat hearts following intravenous administration. Methyl-branching was introduced in (15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) and 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) to inhibit ..beta..-oxidation. The goals of these studies were to correlate the effects of methyl-branching on the incorporation of these agents into the various fatty acid pools and subcellular distribution profiles, and to relate these data to the myocardial retention properties. The properties of BMIPP and DMIPP were compared with the 15-(p-iodophenyl)pentadecanoic acid straight-chain analogue (IPP). Differences in the heart retention of the analogues after intravenous administration in rats correlated with differences observed in subcellular distribution patterns. The dimethyl DMIPP analogue showed the longest retention and the highest association with the mitochondrial and microsomal fractions (34%, 38%) 30 min after injection. These data are in contrast to the rapid clearance of the straight-chain IPP analogue which showed much lower relative association with the mitochondria and microsomes (18%, 15%). The distribution patterns of each analogue in the various lipid pools appeared consistent with the expected capacity of the analogues to be metabolized by ..beta..-oxidation. In contrast to the rapid oxidation of the straight-chain IPP analogue, the 3-monomethyl BMIPP analogue appeared to undergo slower oxidation and clearance, whereas the dimethyl-branched DMIPP analogue was apparatently not catabolized by the myocardium. All three analogues showed some incorporation into triglycerides. The metabolism patterns of the branched analogues reported here may provide useful information in the description of the mechanisms by which BMIPP and DMIPP are retained in rat myocardium.

  16. Mimicking the Nanostructure of Bone: Comparison of Polymeric Process-Directing Agents

    Directory of Open Access Journals (Sweden)

    Laurie B. Gower

    2010-12-01

    Full Text Available The nanostructure of bone has been replicated using a polymer-induced liquid-precursor (PILP mineralization process. This polymer-mediated crystallization process yields intrafibrillar mineralization of collagen with uniaxially-oriented hydroxyapatite crystals. The process-directing agent, an anionic polymer which we propose mimics the acidic non-collagenous proteins associated with bone formation, sequesters calcium and phosphate ions to form amorphous precursor droplets that can infiltrate the interstices of collagen fibrils. In search of a polymeric agent that produces the highest mineral content in the shortest time, we have studied the influence of various acidic polymers on the in vitro mineralization of collagen scaffolds via the PILP process. Among the polymers investigated were poly-L-aspartic acid (PASP, poly-L-glutamic acid (PGLU, polyvinylphosphonic acid (PVPA, and polyacrylic acid (PAA. Our data indicate that PASP and the combination of PGLU/PASP formed stable mineralization solutions, and yielded nano-structured composites with the highest mineral content. Such studies contribute to our goal of preparing biomimetic bone graft substitutes with composition and structure that mimic bone.

  17. Sustained release of radioprotective agents

    International Nuclear Information System (INIS)

    Shani, J.

    1980-11-01

    New pharmaceutical formulations for the sustained release into the G.I. tract of radioprotective agents have been developed by the authors. The experimental method initially consisted in the production of methylcellulose microcapsules. This method failed apparently because of the premature ''explosion'' of the microcapsules and the consequent premature release of massive amounts of the drug. A new method has been developed which consists in drying and pulverising cysteamine and cysteine preparations, mixing them in various proportions with stearic acid and ethylcellulose as carriers. The mixture is then compressed into cylindrical tablets at several pressure values and the leaching rate of the radioprotective agents is then measured by spectrophotometry. The relation between the concentration of the active drug and its rate of release, and the effect on the release rate of the pressure applied to the tablet during its formation were also investigated. Results indicating that the release rate was linearly related to the square root of ''t'' seem to be in agreement with what is predictable, according to Higuchi's equation, save for the very initial and terminal phases. A clear correlation was also established between the stearic acid/ethylcellulose ratios and the release of 20% cysteine, namely a marked decrease in the rate of cysteine release was observed with increasing concentrations of stearic acid. Finally, it was observed that a higher formation pressure results in quicker release of the drug

  18. Fabrication of shape memory natural rubber using palmitic acid

    Directory of Open Access Journals (Sweden)

    Jeff Sze-Hua Wee

    2017-10-01

    Full Text Available This paper investigates the practicability of fabricating a shape memory natural rubber with the use of palmitic acid as the swelling agent. Strips of natural rubber samples were swollen in molten palmitic acid at 75 °C. Equilibrium swelling of natural rubber with palmitic acid was found to occur at approximately 50 min of swelling time. Under cooling effect, the palmitic acid crystallized to form a percolated crystalline platelet network. These networks allow fabricated shape memory natural rubber (SMNR to deform and recover its shape at a temperature above the melting point of palmitic acid. Under controlled uniaxial stress, the natural rubber sample with 0 parts per hundred rubber (phr carbon black loading exhibits fixity and recovery of 80 ± 10%. Motivation of this research is primarily on practicability of palmitic acid to be used as a swelling agent for shape memory properties. Results show that palmitic acid is a relatively good swelling agent to induce shape memory properties into natural rubber.

  19. Early conversion from calcineurin inhibitor- to everolimus-based therapy following kidney transplantation : Results of the randomized ELEVATE trial

    NARCIS (Netherlands)

    de Fijter, Johan W; Holdaas, Hallvard; Øyen, Ole; Sanders, Jan Stephan; Sundar, Sankaran; Bemelman, Frederike J; Sommerer, Claudia; Pascual, Julio; Avihingsanon, Yingyos; Pongskul, Cholatip; Oppenheimer, Frederic; Toselli, Lorenzo; Russ, Graeme; Wang, Zailong; Lopez, Patricia; Kochuparampil, Jossy; Cruzado, Josep M; van der Giet, Markus

    In a 24-month, multicenter, open-label, randomized trial, 715 de novo kidney transplant recipients were randomized at 10-14 weeks to convert to everolimus (n=359) or remain on standard calcineurin inhibitor (CNI) therapy (n=356; 231 tacrolimus; 125 cyclosporine), all with mycophenolic acid and

  20. Compaction agent clarification of microbial lysates

    Science.gov (United States)

    DeWalt, Brad W.; Murphy, Jason C.; Fox, George E.; Willson, Richard C.

    2003-01-01

    Recombinant proteins are often purified from microbial lysates containing high concentrations of nucleic acids. Pre-purification steps such as nuclease addition or precipitation with polyethyleneimine or ammonium sulfate are normally required to reduce viscosity and to eliminate competing polyanions before anion exchange chromatography. We report that small polycationic compaction agents such as spermine selectively precipitate nucleic acids during or after Escherichia coli lysis, allowing DNA and RNA to be pelleted with the insoluble cell debris. Analysis by spectrophotometry and protein assay confirmed a significant reduction in the concentration of nucleic acids present, with preservation of protein. Lysate viscosity is greatly reduced, facilitating subsequent processing. We have used 5mM spermine to remove nucleic acids from E. coli lysate in the purification of a hexahistidine-tagged HIV reverse transcriptase.

  1. Alkalisation agent measurement with differential conductivity method in secondary water system

    International Nuclear Information System (INIS)

    Wuhrmann, Peter; Lendi, Marco

    2012-09-01

    Besides ammonia hydroxide, also morpholine and ethanol-amine (ETA) are mainly used as a pH regulating agent on the secondary water side [1]. The concentration of the alkalisation agent can only be calculated if the chemical composition in the sample is known [2]. Therefore, for a reliable alkalisation agent measurement, there are three major steps to take: A reliable specific and (degassed) acid conductivity measurement, pH calculation and the selection of the chemical model for concentration calculation of the alkalisation agent (authors)

  2. Production of ethoxylated fatty acids derived from Jatropha non-edible oil as a nonionic fat-liquoring agent.

    Science.gov (United States)

    El-Shattory, Y; Abo-Elwafa, Ghada A; Aly, Saadia M; Nashy, El-Shahat H A

    2012-01-01

    Natural fatty derivatives (oleochemicals) have been used as intermediate materials in several industries replacing the harmful and expensive petrochemicals. Fatty ethoxylates are one of these natural fatty derivatives. In the present work Jatropha fatty acids were derived from the non edible Jatropha oil and used as the fat source precursor. The ethoxylation process was carried out on the derived fatty acids using a conventional cheap catalyst (K₂CO₃) in order to obtain economically and naturally valuable non-ionic surfactants. Ethoxylation reaction was proceeded using ethylene oxide gas in the presence of 1 or 2% K₂CO₃ catalyst at 120 and 145°C for 5, 8 and 12 hours. The prepared products were evaluated for their chemical and physical properties as well as its application as non- ionic fat-liquoring agents in leather industry. The obtained results showed that the number of ethylene oxide groups introduced in the fatty acids as well as their EO% increased as the temperature and time of the reaction increased. The highest ethoxylation number was obtained at 145°C for 8 hr. Also, the prepared ethoxylated products were found to be effective fat-liquors with high HLB values giving stable oil in water emulsions. The fat-liquored leather led to an improvement in its mechanical properties such as tensile strength and elongation at break. In addition, a significant enhancement in the texture of the treated leather by the prepared fat-liquors as indicated from the scanning electron microscope (SEM) images was observed.

  3. Treatment of refractory chronic urticaria

    Directory of Open Access Journals (Sweden)

    Aayushi Mehta

    2015-01-01

    Full Text Available Chronic spontaneous urticaria is a distressing disease encountered frequently in clinical practice. The current mainstay of therapy is the use of second-generation, non-sedating antihistamines. However, in patients who do not respond satisfactorily to these agents, a variety of other drugs are used. This article examines the available literature for frequently used agents including systemic corticosteroids, leukotriene receptor antagonists, dapsone, sulfasalazine, hydroxychloroquine, H2 antagonists, methotrexate, cyclosporine A, omalizumab, autologous serum therapy, and mycophenolate mofetil, with an additional focus on publications in Indian literature.

  4. Chelating agents improve enzymatic solubilization of pectinaceous co-processing streams

    DEFF Research Database (Denmark)

    Ravn, Helle Christine; Meyer, Anne S.

    2014-01-01

    of different levels of ethylene-diaminetetraacetic acid (EDTA), citric acid, oxalic acid, and phosphate was assessed in relation to enzymatic solubilization of isopropanol precipitatable oligo- and polysaccharides from sugar beet pulp, citrus peel, and two types of potato pulp. The two types of potato pulp...... solubilization yields. The effect of the chelating agents correlated to their dissociation constants (pKa values) and calcium binding constants and citric acid and EDTA exerted highest effects. Maximum polysaccharide yield was obtained for FiberBind 400 where the enzymatic treatment in presence of citric acid...

  5. Engineering human T cells for resistance to methotrexate and mycophenolate mofetil as an in vivo cell selection strategy.

    Directory of Open Access Journals (Sweden)

    Mahesh Jonnalagadda

    Full Text Available Gene transfer and drug selection systems that enforce ongoing transgene expression in vitro and in vivo which are compatible with human pharmaceutical drugs are currently underdeveloped. Here, we report on the utility of incorporating human enzyme muteins that confer resistance to the lymphotoxic/immunosuppressive drugs methotrexate (MTX and mycophenolate mofetil (MMF in a multicistronic lentiviral vector for in vivo T lymphocyte selection. We found that co-expression of human dihydrofolate reductase (DHFR(FS; L22F, F31S and inosine monophosphate dehydrogenase II (IMPDH2(IY; T333I, S351Y conferred T cell resistance to the cytocidal and anti-proliferative effects of these drugs at concentrations that can be achieved clinically (up to 0.1 µM MTX and 1.0 µM MPA. Furthermore, using a immunodeficient mouse model that supports the engraftment of central memory derived human T cells, in vivo selection studies demonstrate that huEGFRt(+DHFR(FS+IMPDH2(IY+ T cells could be enriched following adoptive transfer either by systemic administration of MTX alone (4.4 -fold, MMF alone (2.9-fold, or combined MTX and MMF (4.9-fold. These findings demonstrate the utility of both DHFR(FS/MTX and IMPDH2(IY/MMF for in vivo selection of lentivirally transduced human T cells. Vectors incorporating these muteins in combination with other therapeutic transgenes may facilitate the selective engraftment of therapeutically active cells in recipients.

  6. Engineering human T cells for resistance to methotrexate and mycophenolate mofetil as an in vivo cell selection strategy.

    Science.gov (United States)

    Jonnalagadda, Mahesh; Brown, Christine E; Chang, Wen-Chung; Ostberg, Julie R; Forman, Stephen J; Jensen, Michael C

    2013-01-01

    Gene transfer and drug selection systems that enforce ongoing transgene expression in vitro and in vivo which are compatible with human pharmaceutical drugs are currently underdeveloped. Here, we report on the utility of incorporating human enzyme muteins that confer resistance to the lymphotoxic/immunosuppressive drugs methotrexate (MTX) and mycophenolate mofetil (MMF) in a multicistronic lentiviral vector for in vivo T lymphocyte selection. We found that co-expression of human dihydrofolate reductase (DHFR(FS); L22F, F31S) and inosine monophosphate dehydrogenase II (IMPDH2(IY); T333I, S351Y) conferred T cell resistance to the cytocidal and anti-proliferative effects of these drugs at concentrations that can be achieved clinically (up to 0.1 µM MTX and 1.0 µM MPA). Furthermore, using a immunodeficient mouse model that supports the engraftment of central memory derived human T cells, in vivo selection studies demonstrate that huEGFRt(+)DHFR(FS+)IMPDH2(IY+) T cells could be enriched following adoptive transfer either by systemic administration of MTX alone (4.4 -fold), MMF alone (2.9-fold), or combined MTX and MMF (4.9-fold). These findings demonstrate the utility of both DHFR(FS)/MTX and IMPDH2(IY)/MMF for in vivo selection of lentivirally transduced human T cells. Vectors incorporating these muteins in combination with other therapeutic transgenes may facilitate the selective engraftment of therapeutically active cells in recipients.

  7. [Decorporation agents for internal radioactive contamination].

    Science.gov (United States)

    Ohmachi, Yasushi

    2015-01-01

    When radionuclides are accidentally ingested or inhaled, blood circulation or tissue/organ deposition of the radionuclides causes systemic or local radiation effects. In such cases, decorporation therapy is used to reduce the health risks due to their intake. Decorporation therapy includes reduction and/or inhibition of absorption from the gastrointestinal tract, isotopic dilution, and the use of diuretics, adsorbents, and chelating agents. For example, penicillamine is recommended as a chelating agent for copper contamination, and diethylene triamine pentaacetic acid is approved for the treatment of internal contamination with plutonium. During chelation therapy, the removal effect of the drugs should be monitored using a whole-body counter and/or bioassay. Some authorities, such as the National Council on Radiation Protection and Measurements and International Atomic Energy Agency, have reported recommended decorporation agents for each radionuclide. However, few drugs are approved by the US Food and Drug Administration, and many are off-label-use agents. Because many decontamination agents are drugs that have been available for a long time and have limited efficacy, the development of new, higher-efficacy drugs has been carried out mainly in the USA and France. In this article, in addition to an outline of decorporation agents for internal radioactive contamination, an outline of our research on decorporation agents for actinide (uranium and plutonium) contamination and for radio-cesium contamination is also presented.

  8. Contrast agent enhanced pQCT of articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Kallioniemi, A S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Jurvelin, J S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Nieminen, M T [Department of Diagnostic Radiology, POB 50, 90029 OYS, Oulu University Hospital, Oulu (Finland); Lammi, M J [Department of Anatomy, Institute of Biomedicine, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Toeyraes, J [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland)

    2007-02-21

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T{sub 1,Gd} and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

  9. Contrast agent enhanced pQCT of articular cartilage

    Science.gov (United States)

    Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

    2007-02-01

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

  10. Contrast agent enhanced pQCT of articular cartilage

    International Nuclear Information System (INIS)

    Kallioniemi, A S; Jurvelin, J S; Nieminen, M T; Lammi, M J; Toeyraes, J

    2007-01-01

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T 1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded

  11. Graphene oxide as a nanocarrier for controlled release and targeted delivery of an anticancer active agent, chlorogenic acid.

    Science.gov (United States)

    Barahuie, Farahnaz; Saifullah, Bullo; Dorniani, Dena; Fakurazi, Sharida; Karthivashan, Govindarajan; Hussein, Mohd Zobir; Elfghi, Fawzi M

    2017-05-01

    We have synthesized graphene oxide using improved Hummer's method in order to explore the potential use of the resulting graphene oxide as a nanocarrier for an active anticancer agent, chlorogenic acid (CA). The synthesized graphene oxide and chlorogenic acid-graphene oxide nanocomposite (CAGO) were characterized using Fourier transform infrared (FTIR) spectroscopy, thermogravimetry and differential thermogravimetry analysis, Raman spectroscopy, powder X-ray diffraction (PXRD), UV-vis spectroscopy and high resolution transmission electron microscopy (HRTEM) techniques. The successful conjugation of chlorogenic acid onto graphene oxide through hydrogen bonding and π-π interaction was confirmed by Raman spectroscopy, FTIR analysis and X-ray diffraction patterns. The loading of CA in the nanohybrid was estimated to be around 13.1% by UV-vis spectroscopy. The release profiles showed favourable, sustained and pH-dependent release of CA from CAGO nanocomposite and conformed well to the pseudo-second order kinetic model. Furthermore, the designed anticancer nanohybrid was thermally more stable than its counterpart. The in vitro cytotoxicity results revealed insignificant toxicity effect towards normal cell line, with a viability of >80% even at higher concentration of 50μg/mL. Contrarily, CAGO nanocomposite revealed enhanced toxic effect towards evaluated cancer cell lines (HepG2 human liver hepatocellular carcinoma cell line, A549 human lung adenocarcinoma epithelial cell line, and HeLa human cervical cancer cell line) compared to its free form. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Uranium recovery from wet process phosphoric acid

    International Nuclear Information System (INIS)

    1980-01-01

    In the field of metallurgy, specifically processes for recovering uranium from wet process phosphoric acid solution derived from the acidulation of uraniferous phosphate ores, problems of imbalance of ion exchange agents, contamination of recycled phosphoric acid with process organics and oxidizing agents, and loss and contamination of uranium product, are solved by removing organics from the raffinate after ion exchange conversion of uranium to uranous form and recovery thereof by ion exchange, and returning organics to the circuit to balance mono and disubstituted ester ion exchange agents; then oxidatively stripping uranium from the agent using hydrogen peroxide; then after ion exchange recovery of uranyl and scrubbing, stripping with sodium carbonate and acidifying the strip solution and using some of it for the scrubbing; regenerating the sodium loaded agent and recycling it to the uranous recovery step. Economic recovery of uranium as a by-product of phosphate fertilizer production is effected. (author)

  13. Studies on removal of plutonium from oxalic acid containing hydrochloric acid solutions

    Energy Technology Data Exchange (ETDEWEB)

    Ghadse, D R; Noronha, D M; Joshi, A R [Fuel Chemistry Division, Bhabha Atomic Research Centre, Mumbai (India)

    1994-06-01

    Solution containing hydrochloric acid, oxalic acid and considerable quantities of plutonium may be generated while recycling of scrap produced during the metallic fuel fabrication. Plutonium from such waste is normally recovered by anion exchange method after the destruction of oxalic acid using suitable oxidising agent. Solvent extraction and ion exchange methods are being explored in this laboratory for recovery of Pu from oxalic acid containing HCl solutions without prior destruction of oxalic acid. This paper describes the results on the determination of distribution ratios for extraction of Pu(IV) from hydrochloric acid using Aliquot-336 or HDEHP under varying experimental conditions. (author). 5 refs., 5 tabs.

  14. I-123-labelled heptadecanoic acid as myocardial imaging agent: comparison with thallium-201 and first-pass nuclear ventriculography

    International Nuclear Information System (INIS)

    Abdullah, A.Z.; Hawkins, L.A.; Britton, K.E.; Elliott, A.T.; Stephens, J.D.

    1981-01-01

    Results of the use of 123 I-iodoheptadecanoic acid (HA) as a myocardial imaging agent in eight patients and six normals are presented. It was shown that 123 I-HA gave comparable results to the widely used radiopharmaceutical 201 Tl. However the advantages of using 123 I-HA are that the 159 KeV energy is better suited to the conventional gamma camera, it gives a lower radiation dose to the patient and has a lower cost per study. 123 I-HA also has an important advantage in its potential for studying regional myocardial metabolic activity; in one patient, a defect due to ischaemia was seen at rest with 123 I-HA but required stress to make it evident with 201 Tl imaging. (U.K.)

  15. Evaluation of liquid-phase oxidation for the destruction of potential chemical terrorism agents

    Energy Technology Data Exchange (ETDEWEB)

    Thouin, G.; Harrison, S.; Li, K.; Kuang, W.; Volchek, K.; Fingas, M. [Environment Canada, Ottawa, ON (Canada). Emergencies Science Div; Potaraju, S.; Velicogna, D.; Obenauf, A. [SAIC Canada, Ottawa, ON (Canada)

    2005-07-01

    Although pesticides are designed to protect crops and livestock against insects, fungi or nuisance plants, the toxicity of these compounds is not limited to target species. Organophosphorus, organochlorine and carbamate pesticides all target the nervous systems of insects. This paper assessed the effectiveness of an enhanced oxidation process using peroxycarboxylic acids for the liquid-phase destruction of toxic industrial chemicals, considered to be potential agents of chemical terrorism. Peroxyacetic acid (PAA) and peroxypropionic acid (PPA) were tested as decontamination agents on organophosphorus, organochlorine and carbamate pesticides. The processes were reviewed in relation to the terms of percent agent destruction over time, with a target of 90 per cent destruction within 30 minutes. Effectiveness was also assessed on the accumulation of toxic by-products. A background of the pesticides was presented, as well as details of their various applications. The molecular structures of the compounds were also provided. Oxidation extraction procedures, materials and methods were also presented, as well as analytical techniques, method detection limits and issues concerning reproducibility. The pH profile of PAA and PPA as a function of the concentration in acid was studied in order to determine which was more likely to be corrosive. It was concluded that peroxycarboxylic acids are effective decontamination agents for organophosphorous and carbamate pesticides. PAA and PPA are equally effective in degrading the examined pesticides, however, greater amounts of toxic by-products are found with PPA than with PAA. Neither PAA nor PPA were able to degrade lindane, and more lindane was found in the treated samples than in the controls. It was noted that time profiles for lower concentrations of peroxycarboxylic acids and pH profiles are currently being developed. It was suggested that further research in this area included degradation experiments on various types of

  16. Kinetics and Mechanism of Bioactivation via S-Oxygenation of Anti-Tubercular Agent Ethionamide by Peracetic Acid.

    Science.gov (United States)

    Chipiso, Kudzanai; Logan, Isabelle E; Eskew, Matthew W; Omondi, Benard; Simoyi, Reuben H

    2016-10-11

    The kinetics and mechanism of the oxidation of the important antitubercular agent, ethionamide, ETA (2-ethylthioisonicotinamide), by peracetic acid (PAA) have been studied. It is effectively a biphasic reaction with an initial rapid first phase of the reaction which is over in about 5 s and a second slower phase of the reaction which can run up to an hour. The first phase involves the addition of a single oxygen atom to ethionamide to form the S-oxide. The second phase involves further oxidation of the S-oxide to desulfurization of ETA to give 2-ethylisonicotinamide. In contrast to the stability of most organosulfur compounds, the S-oxide of ETA is relatively stable and can be isolated. In conditions of excess ETA, the stoichiometry of the reaction was strictly 1:1: CH 3 CO 3 H + Et(C 5 H 4 )C(═S)NH 2 → CH 3 CO 2 H + Et(C 5 H 4 )C(═NH)SOH. In this oxidation, it was apparent that only the sulfur center was the reactive site. Though ETA was ultimately desulfurized, only the S-oxide was stable. Electrospray ionization (ESI) spectral analysis did not detect any substantial formation of the sulfinic and sulfonic acids. This suggests that cleavage of the carbon-sulfur bond occurs at the sulfenic acid stage, resulting in the formation of an unstable sulfur species that can react further to form more stable sulfur species. In this oxidation, no sulfate formation was observed. ESI spectral analysis data showed a final sulfur species in the form of a dimeric sulfur monoxide species, H 3 S 2 O 2 . We derived a bimolecular rate constant for the formation of the S-oxide of (3.08 ± 0.72) × 10 2 M -1 s -1 . Oxidation of the S-oxide further to give 2-ethylisonicotinamide gave zero order kinetics.

  17. Study on folate receptor PET imaging agent 18F-flurophenethyl folate

    International Nuclear Information System (INIS)

    Guo Congying; Zhu Jianhua; Qian Jun; Yang Yang; Shen Haixing; Zhang Zhengwei

    2009-01-01

    This work is aimed at synthesizing an 18 F-labelled folate derivative that can be used as folate-receptor induced tumor PET imaging agent. Under the optimal reaction and testing specification formulated during the cold-labeling experiments, 18 F labeling of folic acid was achieved in three steps of 18 F pre-labeling,bromination and esterification. The receptor binding property of the newly-synthesized folate radio-derivative was studied through β-lactoglobulin binding test. Tumor-bearing nude mice injected with the new compound were used to study whether the derivative can accumulate within tumor issue. Preliminary studies in vitro and in vivo showed that this new PET agent still possessed receptor binding qualities of folic acid. 18 F-flurophenethyl folate remained good affinity and specificity with β-lactoglobulin. Accumulation of activities in tumor tissues was found in tumor-bearing nude mice. A new folate receptor ligand: 18 F-flurophenethyl folate was synthesized,with high yield and good stability. Since the pre-labeling method was used, the fluorine labeling was not directly imposed upon folic acid.In this way, the structure destruction, which happens in high temperature reaction of folic acid, can be avoided. The synthesized folate derivative remained the binding structural quality of folic acid and could bind with the folate-binding protein: β-lactoglobulin. Through the folate receptors located on tumor tissues, 18 F-flurophenethyl folate accumulated in the tumor tissue, exhibiting its potential as a tumor PET imaging agent. (authors)

  18. 3-hydroxy-2(1H)-pyridinone chelating agents

    Science.gov (United States)

    Raymond, K.; Xu, J.

    1999-04-06

    Disclosed is a series of improved chelating agents and the chelates formed from these agents, which are highly effective upon both injection and oral administration. Several of the most effective are of low toxicity. These chelating agents incorporate within their structure 3-hydroxy-2-pyridinone (3,2-HOPO) moieties with a substituted carbamoyl group ortho to the hydroxy group of the hydroxypyridinone ring. The electron-withdrawing carbamoyl group increases the acidity, as well as the chemical stability towards oxidation and reduction, of the hydroxypyridinones. In the metal complexes of the chelating agents, the amide protons form very strong hydrogen bonds with the adjacent HOPO oxygen donor, making these complexes very stable at physiological conditions. The terminal N-substituents provide a certain degree of lipophilicity to the 3,2-HOPO, increasing oral activity. 2 figs.

  19. 42 CFR 73.4 - Overlap select agents and toxins.

    Science.gov (United States)

    2010-10-01

    ... genetically modified. (d) Overlap select agents or toxins that meet any of the following criteria are excluded... Equine Encephalitis virus (c) Genetic Elements, Recombinant Nucleic Acids, and Recombinant Organisms: (1...

  20. 7 CFR 331.3 - PPQ select agents and toxins.

    Science.gov (United States)

    2010-01-01

    ...) Select agents and toxins listed in paragraph (b) of this section that have been genetically modified. (d... variegated chlorosis strain). (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1...

  1. Uranium extraction from phosphoric acid

    International Nuclear Information System (INIS)

    Araujo Figueiredo, C. de

    1984-01-01

    The recovery of uranium from phosphoric liquor by two extraction process is studied. First, uranium is reduced to tetravalent condition and is extracted by dioctypyrophosphoric acid. The re-extraction is made by concentrated phosphoric acid with an oxidizing agent. The re-extract is submitted to the second process and uranium is extracted by di-ethylhexilphosphoric acid and trioctylphosphine oxide. (M.A.C.) [pt

  2. PENGGUNAAN BERBAGAI JENIS BAHAN PELINDUNG UNTUK MEMPERTAHANKAN VIABILITAS BAKTERI ASAM LAKTAT YANG DI ISOLASI DARI AIR SUSU IBU PADA PROSES PENGERINGAN BEKU [Utilization of various cryogenic agents during freeze drying to Maintain the viability of Lactic Acid Bacteria Isolated from breast milk

    Directory of Open Access Journals (Sweden)

    Ni Nyoman Puspawati1*

    2010-06-01

    Full Text Available Lactic acid bacteria are the most important bacteria having potential as probiotic. The objectives of the present study were to examine the growth of Lactic Acid Bacteria, identify the Lactic Acid Bacteria capable of surviving and evaluate the best cryogenic agents that protect the viability of Lactic Acid Bacteria during freeze drying. Four cryogenic agents, i.e. sucrose, lactose, skim milk and maltodextrin, were used in freeze drying of three species of Lactic Acid Bacteria, i.e. Pediococcus pentosaceus A16, Lactobacillus brevis A17 and Lactobacillus rhamnosus R21 isolated from breast milk. Evaluation included viability before and after freeze drying, survival of freeze dried culture in 0.5 % bile salt and low pH for 5 hours. The result showed that three of cryogenics, i.e. sucrose, lactose and skim milk improved the viability of freeze dried of all lactobacilli, except maltodextrin that did not give protection to L. rhamnosus R21. Evaluation on the survival of LAB in 0.5 % bile salt showed that cryogenic agents improved the survival rate of all Lactic Acid Bacteria during freeze drying. The cryogenic also improved the survival rate of LAB at low pH, with the best protection given by skim milk on L. rhamnosus R21.

  3. Olivine-type cathode for rechargeable batteries: Role of chelating agents

    International Nuclear Information System (INIS)

    Kandhasamy, Sathiyaraj; Singh, Pritam; Thurgate, Stephen; Ionescu, Mihail; Appadoo, Dominique; Minakshi, Manickam

    2012-01-01

    Highlights: ► Olivine powder was synthesized by sol–gel method using a range of chelating agents. ► Role of chelating agents in olivine cathode was investigated for battery application. ► Battery was fabricated with olivine cathode, Zn anode and aqueous electrolyte. ► Synergetic effect of additives (CA + TEA + PVP) led to improved storage capacity. - Abstract: Olivine (LiCo 1/3 Mn 1/3 Ni 1/3 PO 4 ) powders were synthesized at 550–600 °C for 6 h in air by a sol–gel method using multiple chelating agents and used as a cathode material for rechargeable batteries. Range of chelating agents like a weak organic acid (citric acid – CA), emulsifier (triethanolamine – TEA) and non-ionic surfactant (polyvinylpyrrolidone – PVP) in sol–gel wet chemical synthesis were used. The dependence of the physicochemical properties of the olivine powders such as particle size, morphology, structural bonding and crystallinity on the chelating agent was extensively investigated. Among the chelating agents used, unique cycling behavior (75 mAh/g after 25 cycles) is observed for the PVP assisted olivine. This is due to volumetric change in trapped organic layer for first few cycles. The trapped organic species in the electrode–electrolyte interface enhances the rate of lithium ion diffusion with better capacity retention. In contrast, CA and TEA showed a gradual capacity fade of 30 and 38 mAh/g respectively after multiple cycles. The combination of all the three mixed chelating agents showed an excellent electrochemical behavior of 100 mAh/g after multiple cycles and the synergistic effect of these agents are discussed.

  4. Failure to preserve beta-cell function with mycophenolate mofetil and daclizumab combined therapy in patients with new- onset type 1 diabetes.

    Science.gov (United States)

    Gottlieb, Peter A; Quinlan, Scott; Krause-Steinrauf, Heidi; Greenbaum, Carla J; Wilson, Darrell M; Rodriguez, Henry; Schatz, Desmond A; Moran, Antoinette M; Lachin, John M; Skyler, Jay S

    2010-04-01

    This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing beta-cells in subjects with new-onset type 1 diabetes. A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process.

  5. Failure to Preserve β-Cell Function With Mycophenolate Mofetil and Daclizumab Combined Therapy in Patients With New- Onset Type 1 Diabetes

    Science.gov (United States)

    Gottlieb, Peter A.; Quinlan, Scott; Krause-Steinrauf, Heidi; Greenbaum, Carla J.; Wilson, Darrell M.; Rodriguez, Henry; Schatz, Desmond A.; Moran, Antoinette M.; Lachin, John M.; Skyler, Jay S.

    2010-01-01

    OBJECTIVE This trial tested whether mycophenolate mofetil (MMF) alone or with daclizumab (DZB) could arrest the loss of insulin-producing β-cells in subjects with new-onset type 1 diabetes. RESEARCH DESIGN AND METHODS A multi-center, randomized, placebo-controlled, double-masked trial was initiated by Type 1 Diabetes TrialNet at 13 sites in North America and Europe. Subjects diagnosed with type 1 diabetes and with sufficient C-peptide within 3 months of diagnosis were randomized to either MMF alone, MMF plus DZB, or placebo, and then followed for 2 years. The primary outcome was the geometric mean area under the curve (AUC) C-peptide from the 2-h mixed meal tolerance test. RESULTS One hundred and twenty-six subjects were randomized and treated during the trial. The geometric mean C-peptide AUC at 2 years was unaffected by MMF alone or MMF plus DZB versus placebo. Adverse events were more frequent in the active therapy groups relative to the control group, but not significantly. CONCLUSIONS Neither MMF alone nor MMF in combination with DZB had an effect on the loss of C-peptide in subjects with new-onset type 1 diabetes. Higher doses or more targeted immunotherapies may be needed to affect the autoimmune process. PMID:20067954

  6. DMXAA: An antivascular agent with multiple host responses

    International Nuclear Information System (INIS)

    Baguley, Bruce C.; Ching, L.-M.

    2002-01-01

    Purpose: To measure host responses to the antivascular agent DMXAA (5,6-dimethylxanthenone-4-acetic acid) and to compare them with those of other antivascular agents. Methods: Induction of tumor necrosis was measured in s.c. murine Colon 38 carcinomas growing in normal or tumor necrosis factor (TNF) receptor-1 knockout mice. Plasma and tumor tissue TNF concentrations were measured by ELISA. Plasma concentrations of 5-hydroxyindoleacetic acid (as a measure of serotonin release) and nitrite (as a measure of nitric oxide release) were measured by high-performance liquid chromatography. Results: Administration of DMXAA to tumor-bearing mice increased plasma and tumor tissue-associated TNF, in addition to increasing plasma nitric oxide, distinguishing its action from that of mitotic poisons that had an antivascular action. Results from TNF receptor-1 knockout mice showed that TNF played an important role in both its antitumor action and its host toxicity. Release of serotonin occurred in response to mitotic poisons, as well as to DMXAA. Conclusions: The antivascular action of DMXAA involves in situ production in tumor tissue of a cascade of vasoactive events, including a direct effect on vascular endothelial cells and indirect vascular effects involving TNF, other cytokines, serotonin, and nitric oxide. Now that Phase I clinical trials of DMXAA are completed, the optimization of this cascade in cancer patients is a major challenge. Plasma 5-hydroxyindoleacetic acid concentrations may provide a useful surrogate marker for the antivascular effects of DMXAA and other antivascular agents

  7. Process for recovering a uranium containing concentrate and purified phosphoric acid from a wet process phosphoric acid containing uranium

    International Nuclear Information System (INIS)

    Weterings, C.A.M.; Janssen, J.A.

    1985-01-01

    A process is claimed for recovering from a wet process phosphoric acid which contains uranium, a uranium containing concentrate and a purified phosphoric acid. The wet process phosphoric acid is treated with a precipitant in the presence of a reducing agent and an aliphatic ketone

  8. Process for recovering a uranium containing concentrate and purified phosphoric acid from a wet process phosphoric acid containing uranium

    Energy Technology Data Exchange (ETDEWEB)

    Weterings, C.A.M.; Janssen, J.A.

    1985-04-30

    A process is claimed for recovering from a wet process phosphoric acid which contains uranium, a uranium containing concentrate and a purified phosphoric acid. The wet process phosphoric acid is treated with a precipitant in the presence of a reducing agent and an aliphatic ketone.

  9. Extended release formulations for local anaesthetic agents.

    Science.gov (United States)

    Weiniger, C F; Golovanevski, L; Domb, A J; Ickowicz, D

    2012-08-01

    Systemic toxicity through overdose of local anaesthetic agents is a real concern. By encapsulating local anaesthetics in biodegradable carriers to produce a system for prolonged release, their duration of action can be extended. This encapsulation should also improve the safety profile of the local anaesthetic as it is released at a slower rate. Work with naturally occurring local anaestheticss has also shown promise in the area of reducing systemic and neurotoxicity. Extended duration local anaesthetic formulations in current development or clinical use include liposomes, hydrophobic based polymer particles such as Poly(lactic-co-glycolic acid) microspheres, pasty injectable and solid polymers like Poly(sebacic-co-ricinoleic acid) P(SA:RA) and their combination with synthetic and natural local anaesthetic. Their duration of action, rationale and limitations are reviewed. Direct comparison of the different agents is limited by their chemical properties, the drug doses encapsulated and the details of in vivo models described. Anaesthesia © 2012 The Association of Anaesthetists of Great Britain and Ireland.

  10. Extraction of rare earth elements from a contaminated cropland soil using nitric acid, citric acid, and EDTA.

    Science.gov (United States)

    Tang, Hailong; Shuai, Weitao; Wang, Xiaojing; Liu, Yangsheng

    2017-08-01

    Rare earth elements (REEs) contamination to the surrounding soil has increased the concerns of health risk to the local residents. Soil washing was first attempted in our study to remediate REEs-contaminated cropland soil using nitric acid, citric acid, and ethylene diamine tetraacetic acid (EDTA) for soil decontamination and possible recovery of REEs. The extraction time, washing agent concentration, and pH value of the washing solution were optimized. The sequential extraction analysis proposed by Tessier was adopted to study the speciation changes of the REEs before and after soil washing. The extract containing citric acid was dried to obtain solid for the X-ray fluorescence (XRF) analysis. The results revealed that the optimal extraction time was 72 h, and the REEs extraction efficiency increased as the agent concentration increased from 0.01 to 0.1 mol/L. EDTA was efficient to extract REEs over a wide range of pH values, while citric acid was around pH 6.0. Under optimized conditions, the average extraction efficiencies of the major REEs in the contaminated soil were 70.96%, 64.38%, and 62.12% by EDTA, nitric acid, and citric acid, respectively. The sequential extraction analyses revealed that most soil-bounded REEs were mobilized or extracted except for those in the residual fraction. Under a comprehensive consideration of the extraction efficiency and the environmental impact, citric acid was recommended as the most suitable agent for extraction of the REEs from the contaminated cropland soils. The XRF analysis revealed that Mn, Al, Si, Pb, Fe, and REEs were the major elements in the extract indicating a possibile recovery of the REEs.

  11. In vitro cytotoxic and genotoxic effects of diphenylarsinic acid, a degradation product of chemical warfare agents

    International Nuclear Information System (INIS)

    Ochi, Takafumi; Suzuki, Toshihide; Isono, Hideo; Kaise, Toshikazu

    2004-01-01

    Diphenylarsinic acid [DPAs(V)], a degradation product of diphenylcyanoarsine or diphenylchloroarsine, both of which were developed as chemical warfare agents, was investigated in terms of its capacity to induce cytotoxic effects, numerical and structural changes of chromosomes, and abnormalities of centrosome integrity and spindle organizations in conjunction with the effects of glutathione (GSH) depletion. DPAs(V) had toxic effects on cultured human hepatocarcinoma HepG2 cells at concentrations more than 0.5 mM. Depletion of GSH reduced the toxic effects of DPAs(V) as well as dimethylarsinic acid [DMAs(V)] toxicity, while toxicity by arsenite [iAs(III)] was enhanced. Exogenously added sulfhydryl (SH) compounds, such as dimercapropropane sulfonate (DMPS), GSH, and dithiothreitol (DTT), enhanced the toxic effects of DPAs(V) while they suppressed iAs(III) toxicity. DPAs(V) caused an increase in the mitotic index, and also structural and numerical changes in chromosomes in V79 Chinese hamster cells. Abnormality of centrosome integrity in mitotic V79 cells and multipolar spindles was also induced by DPAs(V) in a time- and concentration-dependent manner. These results suggested that highly toxic chemicals were generated by the interaction of DPAs(V) with SH compounds. Moreover, enhancements of toxicity by a combination of DPAs(V) and SH compounds suggested a risk in the use of SH compounds as a remedy for intoxication by diphenylarsenic compounds. Investigations on the effects of SH compounds on animals intoxicated with DPAs(V) are warranted

  12. In vitro cytotoxic and genotoxic effects of diphenylarsinic acid, a degradation product of chemical warfare agents

    Energy Technology Data Exchange (ETDEWEB)

    Ochi, Takafumi; Suzuki, Toshihide; Isono, Hideo; Kaise, Toshikazu

    2004-10-01

    Diphenylarsinic acid [DPAs(V)], a degradation product of diphenylcyanoarsine or diphenylchloroarsine, both of which were developed as chemical warfare agents, was investigated in terms of its capacity to induce cytotoxic effects, numerical and structural changes of chromosomes, and abnormalities of centrosome integrity and spindle organizations in conjunction with the effects of glutathione (GSH) depletion. DPAs(V) had toxic effects on cultured human hepatocarcinoma HepG2 cells at concentrations more than 0.5 mM. Depletion of GSH reduced the toxic effects of DPAs(V) as well as dimethylarsinic acid [DMAs(V)] toxicity, while toxicity by arsenite [iAs(III)] was enhanced. Exogenously added sulfhydryl (SH) compounds, such as dimercapropropane sulfonate (DMPS), GSH, and dithiothreitol (DTT), enhanced the toxic effects of DPAs(V) while they suppressed iAs(III) toxicity. DPAs(V) caused an increase in the mitotic index, and also structural and numerical changes in chromosomes in V79 Chinese hamster cells. Abnormality of centrosome integrity in mitotic V79 cells and multipolar spindles was also induced by DPAs(V) in a time- and concentration-dependent manner. These results suggested that highly toxic chemicals were generated by the interaction of DPAs(V) with SH compounds. Moreover, enhancements of toxicity by a combination of DPAs(V) and SH compounds suggested a risk in the use of SH compounds as a remedy for intoxication by diphenylarsenic compounds. Investigations on the effects of SH compounds on animals intoxicated with DPAs(V) are warranted.

  13. A Bayesian Analysis of a Randomized Clinical Trial Comparing Antimetabolite Therapies for Non-Infectious Uveitis.

    Science.gov (United States)

    Browne, Erica N; Rathinam, Sivakumar R; Kanakath, Anuradha; Thundikandy, Radhika; Babu, Manohar; Lietman, Thomas M; Acharya, Nisha R

    2017-02-01

    To conduct a Bayesian analysis of a randomized clinical trial (RCT) for non-infectious uveitis using expert opinion as a subjective prior belief. A RCT was conducted to determine which antimetabolite, methotrexate or mycophenolate mofetil, is more effective as an initial corticosteroid-sparing agent for the treatment of intermediate, posterior, and pan-uveitis. Before the release of trial results, expert opinion on the relative effectiveness of these two medications was collected via online survey. Members of the American Uveitis Society executive committee were invited to provide an estimate for the relative decrease in efficacy with a 95% credible interval (CrI). A prior probability distribution was created from experts' estimates. A Bayesian analysis was performed using the constructed expert prior probability distribution and the trial's primary outcome. A total of 11 of the 12 invited uveitis specialists provided estimates. Eight of 11 experts (73%) believed mycophenolate mofetil is more effective. The group prior belief was that the odds of treatment success for patients taking mycophenolate mofetil were 1.4-fold the odds of those taking methotrexate (95% CrI 0.03-45.0). The odds of treatment success with mycophenolate mofetil compared to methotrexate was 0.4 from the RCT (95% confidence interval 0.1-1.2) and 0.7 (95% CrI 0.2-1.7) from the Bayesian analysis. A Bayesian analysis combining expert belief with the trial's result did not indicate preference for one drug. However, the wide credible interval leaves open the possibility of a substantial treatment effect. This suggests clinical equipoise necessary to allow a larger, more definitive RCT.

  14. Both the Jasmonic Acid and the Salicylic Acid Pathways Contribute to Resistance to the Biotrophic Clubroot Agent Plasmodiophora brassicae in Arabidopsis.

    Science.gov (United States)

    Lemarié, Séverine; Robert-Seilaniantz, Alexandre; Lariagon, Christine; Lemoine, Jocelyne; Marnet, Nathalie; Jubault, Mélanie; Manzanares-Dauleux, Maria J; Gravot, Antoine

    2015-11-01

    The role of salicylic acid (SA) and jasmonic acid (JA) signaling in resistance to root pathogens has been poorly documented. We assessed the contribution of SA and JA to basal and partial resistance of Arabidopsis to the biotrophic clubroot agent Plasmodiophora brassicae. SA and JA levels as well as the expression of the SA-responsive genes PR2 and PR5 and the JA-responsive genes ARGAH2 and THI2.1 were monitored in infected roots of the accessions Col-0 (susceptible) and Bur-0 (partially resistant). SA signaling was activated in Bur-0 but not in Col-0. The JA pathway was weakly activated in Bur-0 but was strongly induced in Col-0. The contribution of both pathways to clubroot resistance was then assessed using exogenous phytohormone application and mutants affected in SA or JA signaling. Exogenous SA treatment decreased clubroot symptoms in the two Arabidopsis accessions, whereas JA treatment reduced clubroot symptoms only in Col-0. The cpr5-2 mutant, in which SA responses are constitutively induced, was more resistant to clubroot than the corresponding wild type, and the JA signaling-deficient mutant jar1 was more susceptible. Finally, we showed that the JA-mediated induction of NATA1 drove N(δ)-acetylornithine biosynthesis in infected Col-0 roots. The 35S::NATA1 and nata1 lines displayed reduced or enhanced clubroot symptoms, respectively, thus suggesting that in Col-0 this pathway was involved in the JA-mediated basal clubroot resistance. Overall, our data support the idea that, depending on the Arabidopsis accession, both SA and JA signaling can play a role in partial inhibition of clubroot development in compatible interactions with P. brassicae. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  15. Military chemical warfare agent human subjects testing: part 2--long-term health effects among participants of U.S. military chemical warfare agent testing.

    Science.gov (United States)

    Brown, Mark

    2009-10-01

    Military chemical warfare agent testing from World War I to 1975 produced thousands of veterans with concerns about how their participation affected their health. A companion article describes the history of these experiments, and how the lack of clinical data hampers evaluation of long-term health consequences. Conversely, much information is available about specific agents tested and their long-term health effects in other populations, which may be invaluable for helping clinicians respond effectively to the health care and other needs of affected veterans. The following review describes tested agents and their known long-term health consequences. Although hundreds of chemicals were tested, they fall into only about a half-dozen pharmaceutical classes, including common pharmaceuticals; anticholinesterase agents including military nerve agents and pesticides; anticholinergic glycolic acid esters such as atropine; acetylcholine reactivators such as 2-PAM; psychoactive compounds including cannabinoids, phencyclidine, and LSD; and irritants including tear gas and riot control agents.

  16. Nucleic Acid-Based Nanoconstructs

    Science.gov (United States)

    Focuses on the design, synthesis, characterization, and development of spherical nucleic acid constructs as effective nanotherapeutic, single-entity agents for the treatment of glioblastoma multiforme and prostate cancers.

  17. Replica of human dentin treated with different desensitizing agents: a methodological SEM study in vitro

    Directory of Open Access Journals (Sweden)

    Pereira Jose Carlos

    2002-01-01

    Full Text Available This is a preliminary study to determine a methodological sequence in vitro which may allow the reproduction of dentin for SEM analysis, after the use of different desensitizing agents. Dentin discs obtained from extracted human third molars were etched with 6% citric acid, an artificial smear layer was created and the surface dentin discs were divided into four quadrants. Quadrants 2, 3 and 4 of each disc were conditioned with 6% citric acid. The desensitizing agents (Oxa-Gel®, Gluma Desensitizer and an experimental agent were applied to quadrants 3 and 4. To evaluate the acid resistance of the treatment, quadrant 4 was etched again with 6% citric acid. An impression was then taken with Aquasil ULV. After a setting period of 6 min, each disc was removed from the impression and stored in a moist-free environment for 24 h at 37ºC. After that time, a low-viscosity epoxy resin (Araltec GY 1109 BR was poured into the impression and cured for 24 h. All specimens were metal-coated for SEM analysis. Comparison of the photomicrographs of dentin discs with their respective impressions and resin replicas showed that this technique can reproduce the characteristics of the dentin surface treated with desensitizing agents.

  18. Removal lead (Pb and mercury (Hg from juaro fish (Pangasius polyuranodon using citric acid from pineapple extract (Ananas comosus as chelating agent

    Directory of Open Access Journals (Sweden)

    Pra Dian Mariadi

    2017-10-01

    Full Text Available An assessment of dietary risk of heavy metals exposure to human is important since it is the main of exposure. The aim of study to measure the contamination of lead and mercury in juaro fish meat and the effort to reduce contaminations using citric acid from pineapple extract as a chelating agent. Samples was soaked and boiled in citric acid extract at concentration 50%, 75 %, 100 % for, 15 min, 30 min, 45 min at 25 0C, 50 0C and 100 0C. The concentration of lead and mercury in Juaro fish lower than the maximum acceptable lever for Pb and Hg respectively (1mg/kg for Pb, 0,5 mg/Kg for Hg. The result indicated that after soaking and boiling in citric acid solution form pineapple extract at concentration 100 % for 45 min at 100 0C reducing heavy metals Pb from 0,02 mg.Kg-1 to 0,003 mg.Kg-1 and Hg from 0,011 mg.Kg-1 to lower than 0,0001 mg.Kg-1. The increasing of soaking time and boiling temperature, the levels of Pb and Hg in Juaro fish Tissue will decreasing.

  19. Neuroprotective effect of p-coumaric acid in rat model of embolic cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Mustafa Guven

    2015-04-01

    Conclusion:Our results showed that p-coumaric acid is a neuroprotective agent on account of its strong anti-oxidant and anti-apoptotic features. Moreover, p-coumaric acid decreased the focal ischemia. Extra effort should be made to introduce p-coumaric acid as a promising therapeutic agent to be utilized for treatment of human cerebral ischemia in the future.

  20. Amino acids and glycine ethyl ester as new crystallization reagents for lysozyme

    International Nuclear Information System (INIS)

    Ito, Len; Shiraki, Kentaro; Yamaguchi, Hiroshi

    2010-01-01

    During the past two decades, amino acids and amino-acid derivatives have been applied in various fields of protein chemistry. The potential use of amino acids and their derivatives as new precipitating agents is described. Several amino acids and their derivatives are prominent additives in the field of protein chemistry. This study reports the use of charged amino acids and glycine ethyl ester as precipitants in protein crystallization, using hen egg-white lysozyme (HEWL) as a model. A discussion of the crystallization of HEWL using these reagents as precipitating agents is given

  1. A New Multichelating Acid System for High-Temperature Sandstone Reservoirs

    Directory of Open Access Journals (Sweden)

    Nianyin Li

    2015-01-01

    Full Text Available Sandstone reservoir acidizing is a complex and heterogeneous acid-rock reaction process. If improper acid treatment is implemented, further damage can be induced instead of removing the initial plug, particularly in high-temperature sandstone reservoirs. An efficient acid system is the key to successful acid treatment. High-temperature sandstone treatment with conventional mud acid system faces problems including high acid-rock reaction rate, short acid effective distance, susceptibility to secondary damage, and serious corrosion to pipelines. In this paper, a new multichelating acid system has been developed to overcome these shortcomings. The acid system is composed of ternary weak acid, organic phosphonic chelating agent, anionic polycarboxylic acid chelating dispersant, fluoride, and other assisted additives. Hydrogen ion slowly released by multistage ionization in ternary weak acid and organic phosphonic within the system decreases the concentration of HF to achieve retardation. Chelating agent and chelating dispersant within the system inhibited anodic and cathodic reaction, respectively, to protect the metal from corrosion, while chelating dispersant has great chelating ability on iron ions, restricting the depolarization reaction of ferric ion and metal. The synergic effect of chelating agent and chelating dispersant removes sulfate scale precipitation and inhibits or decreases potential precipitation such as CaF2, silica gel, and fluosilicate. Mechanisms of retardation, corrosion-inhibition, and scale-removing features have been discussed and evaluated with laboratory tests. Test results indicate that this novel acid system has good overall performance, addressing the technical problems and improving the acidizing effect as well for high-temperature sandstone.

  2. On the Use of Potential Denaturing Agents for Ethanol in Direct Ethanol Fuel Cells

    Directory of Open Access Journals (Sweden)

    Domnik Bayer

    2011-01-01

    Full Text Available Acidic or alkaline direct ethanol fuel cells (DEFCs can be a sustainable alternative for power generation if they are fuelled with bio-ethanol. However, in order to keep the fuel cheap, ethanol has to be exempted from tax on spirits by denaturing. In this investigation the potential denaturing agents fusel oil, tert-butyl ethyl ether, and Bitrex were tested with regard to their compatibility with fuel cells. Experiments were carried out both in sulphuric acid and potassium hydroxide solution. Beside, basic electrochemical tests, differential electrochemical mass spectrometry (DEMS and fuel cell tests were conducted. It was found that fusel oil is not suitable as denaturing agent for DEFC. However, tert-butyl ethyl ether does not seem to hinder the ethanol conversion as much. Finally, a mixture of tert-butyl ethyl ether and Bitrex can be proposed as promising candidate as denaturing agent for use in acidic and alkaline DEFC.

  3. Optimal Contrast Agent Staining of Ligaments and Tendons for X-Ray Computed Tomography.

    Science.gov (United States)

    Balint, Richard; Lowe, Tristan; Shearer, Tom

    2016-01-01

    X-ray computed tomography has become an important tool for studying the microstructures of biological soft tissues, such as ligaments and tendons. Due to the low X-ray attenuation of such tissues, chemical contrast agents are often necessary to enhance contrast during scanning. In this article, the effects of using three different contrast agents--iodine potassium iodide solution, phosphotungstic acid and phosphomolybdic acid--are evaluated and compared. Porcine anterior cruciate ligaments, patellar tendons, medial collateral ligaments and lateral collateral ligaments were used as the basis of the study. Three samples of each of the four ligament/tendon types were each assigned a different contrast agent (giving a total of twelve samples), and the progression of that agent through the tissue was monitored by performing a scan every day for a total period of five days (giving a total of sixty scans). Since the samples were unstained on day one, they had been stained for a total of four days by the time of the final scans. The relative contrast enhancement and tissue deformation were measured. It was observed that the iodine potassium iodide solution penetrated the samples fastest and caused the least sample shrinkage on average (although significant deformation was observed by the time of the final scans), whereas the phosphomolybdic acid caused the greatest sample shrinkage. Equations describing the observed behaviour of the contrast agents, which can be used to predict optimal staining times for ligament and tendon X-ray computed tomography, are presented.

  4. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development.

    Science.gov (United States)

    Smelick, Gillian S; Heffron, Timothy P; Chu, Laura; Dean, Brian; West, David A; Duvall, Scott L; Lum, Bert L; Budha, Nageshwar; Holden, Scott N; Benet, Leslie Z; Frymoyer, Adam; Dresser, Mark J; Ware, Joseph A

    2013-11-04

    Acid-reducing agents (ARAs) are the most commonly prescribed medications in North America and Western Europe. There are currently no data describing the prevalence of their use among cancer patients. However, this is a paramount question due to the potential for significant drug-drug interactions (DDIs) between ARAs, most commonly proton pump inhibitors (PPIs), and orally administered cancer therapeutics that display pH-dependent solubility, which may lead to decreased drug absorption and decreased therapeutic benefit. Of recently approved orally administered cancer therapeutics, >50% are characterized as having pH-dependent solubility, but there are currently no data describing the potential for this ARA-DDI liability among targeted agents currently in clinical development. The objectives of this study were to (1) determine the prevalence of ARA use among different cancer populations and (2) investigate the prevalence of orally administered cancer therapeutics currently in development that may be liable for an ARA-DDI. To address the question of ARA use among cancer patients, a retrospective cross-sectional analysis was performed using two large healthcare databases: Thomson Reuters MarketScan (N = 1,776,443) and the U.S. Department of Veterans Affairs (VA, N = 1,171,833). Among all cancer patients, the total prevalence proportion of ARA use (no. of cancer patients receiving an ARA/total no. of cancer patients) was 20% and 33% for the MarketScan and VA databases, respectively. PPIs were the most commonly prescribed agent, comprising 79% and 65% of all cancer patients receiving a prescription for an ARA (no. of cancer patients receiving a PPI /no. of cancer patients receiving an ARA) for the MarketScan and VA databases, respectively. To estimate the ARA-DDI liability of orally administered molecular targeted cancer therapeutics currently in development, two publicly available databases, (1) Kinase SARfari and (2) canSAR, were examined. For those orally administered

  5. Nanofiber mats composed of a chitosan-poly(d,l-lactic-co-glycolic acid)-poly(ethylene oxide) blend as a postoperative anti-adhesion agent.

    Science.gov (United States)

    Ko, Jae Eok; Ko, Young-Gwang; Kim, Won Il; Kwon, Oh Kyoung; Kwon, Oh Hyeong

    2017-10-01

    Postoperative tissue adhesion causes serious complications and suffering in 90% of patients after peritoneum surgery, while commercial anti-adhesion agents cannot completely prevent postoperative peritoneal adhesions. This study demonstrates electrospining of a blended solution of chitosan, poly(d,l-lactic-co-glycolic acid) (PLGA), and poly(ethylene oxide) (PEO) to fabricate a chitosan-based nanofibrous mat as a postoperative anti-adhesion agent. Rheological studies combined with scanning electron microscopy reveal that the spinnability of the chitosan-PLGA solution could be controlled by adjusting the blend ratio and concentration with average fiber diameter from 634 to 913 nm. Biodegradation of the nanofiber specimens showed accelerated hydrolysis by chitosan. Proliferation of fibroblasts and antimicrobial activity of nanofibers containing chitosan was analyzed. Abdominal defects with cecum adhesion in rats demonstrated that the blend nanofiber mats were effective in preventing tissue adhesion as a barrier (4 weeks after abdominal surgery) by coverage of exfoliated peritoneum and insufficient wound sites at the beginning of the wound healing process. Chitosan-PLGA-PEO blend nanofiber mats will provide a promising key as a postoperative anti-adhesion agent. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1906-1915, 2017. © 2016 Wiley Periodicals, Inc.

  6. Synthesis and evaluation of radioiodinated (E)-18-iodo-17-octadecenoic acid as a model iodoalkenyl fatty acid for myocardial imaging

    International Nuclear Information System (INIS)

    Knapp, F.F. Jr.; Goodman, M.M.; Kabalka, G.W.; Sastry, K.A.

    1984-01-01

    125 I-labeled (E)-18-iodo-17-octadecenoic acid (13) has been prepared and evaluated in rats to determine the myocardial uptake and retention and degree of in vivo deiodination of this model iodovinyl-substituted fatty acid, which contains no structural perturbation to inhibit metabolism. This new agent was prepared by NaI-chloramine-T treatment of (17-carbomethoxyheptadec-1-en-1-yl)boronic acid (11) prepared by catecholborane treatment of methyl 17-octadecynoate (10), followed by basic hydrolysis to the free acid (13). The pivotal substrate, 17-octadecynoic acid (9), was prepared by two new routes. The 125 I-labeled acid 13 showed high myocardial uptake (1 h, 1.90-2.28% dose/g) with 45% washout after 2 h but lower heart/blood ratios in comparison to analogues containing the tellurium heteroatom. Deiodination was low for the first 2 h after injection (2 h, 61% dose/g). Excellent myocardial images were obtained in a dog with the 123 I-labeled agent

  7. Geochemical behaviour of palladium in soils and Pd/PdO model substances in the presence of the organic complexing agents L-methionine and citric acid.

    Science.gov (United States)

    Zereini, Fathi; Wiseman, Clare L S; Vang, My; Albers, Peter; Schneider, Wolfgang; Schindl, Roland; Leopold, Kerstin

    2016-01-01

    Risk assessments of platinum group metal (PGE) emissions, notably those of platinum (Pt), palladium (Pd) and rhodium (Rh), have been mostly based on data regarding the metallic forms used in vehicular exhaust converters, known to be virtually biologically inert and immobile. To adequately assess the potential impacts of PGE, however, data on the chemical behaviour of these metals under ambient conditions post-emission is needed. Complexing agents with a high affinity for metals in the environment are hypothesized to contribute to an increased bioaccessibility of PGE. The purpose of this study is to examine the modulating effects of the organic complexing agents, L-methionine and citric acid, on the geochemical behavior of Pd in soils and model substances (Pd black and PdO). Batch experimental tests were conducted with soils and model substances to examine the impacts of the concentration of complexing agents, pH and length of extraction period on Pd solubility and its chemical transformation. Particle surface chemistry was examined using X-ray photoelectron spectroscopy (XPS) on samples treated with solutions under various conditions, including low and high O2 levels. Pd was observed to be more soluble in the presence of organic complexing agents, compared to Pt and Rh. Pd in soils was more readily solubilized with organic complexing agents compared to the model substances. After 7 days of extraction, L-methionine (0.1 M) treated soil and Pd black samples, for instance, had mean soluble Pd fractions of 12.4 ± 5.9% and 0.554 ± 0.024%, respectively. Surface chemistry analyses (XPS) confirmed the oxidation of metallic Pd surfaces when treated with organic complexing agents. The type of organic complexing agent used for experimental purposes was observed to be the most important factor influencing solubility, followed by solution pH and time of extraction. The results demonstrate that metallic Pd can be transformed into more bioaccessible species in the presence of

  8. Rates of nickel(II) capture from complexes with NTA, EDDA, and related tetradentate chelating agents by the hexadentate chelating agents EDTA and CDTA: Evidence of a "semijunctive" ligand exchange pathway

    Science.gov (United States)

    Boland, Nathan E.; Stone, Alan T.

    2017-09-01

    Many siderophores and metallophores produced by soil organisms, as well as anthropogenic chelating agent soil amendments, rely upon amine and carboxylate Lewis base groups for metal ion binding. UV-visible spectra of metal ion-chelating agent complexes are often similar and, as a consequence, whole-sample absorbance measurements are an unreliable means of monitoring the progress of exchange reactions. In the present work, we employ capillary electrophoresis to physically separate Ni(II)-tetradentate chelating agent complexes (NiL) from Ni(II)-hexadentate chelating agent complexes (NiY) prior to UV detection, such that progress of the reaction NiL + Y → NiY + L can be conveniently monitored. Rates of ligand exchange for Ni(II) are lower than for other +II transition metal ions. Ni(II) speciation in environmental media is often under kinetic rather than equilibrium control. Nitrilotriacetic acid (NTA), with three carboxylate groups all tethered to a central amine Lewis base group, ethylenediamine-N,N‧-diacetic acid (EDDA), with carboxylate-amine-amine-carboxylate groups arranged linearly, plus four structurally related compounds, are used as tetradentate chelating agents. Ethylenediaminetetraacetic acid (EDTA) and the structurally more rigid analog trans-cyclohexaneethylenediaminetetraacetic acid (CDTA) are used as hexadentate chelating agents. Effects of pH and reactant concentration are explored. Ni(II) capture by EDTA was consistently more than an order of magnitude faster than capture by CDTA, and too fast to quantify using our capillary electrophoresis-based technique. Using NiNTA as a reactant, Ni(II) capture by CDTA is independent of CDTA concentration and greatly enhanced by a proton-catalyzed pathway at low pH. Using NiEDDA as reactant, Ni(II) capture by CDTA is first order with respect to CDTA concentration, and the contribution from the proton-catalyzed pathway diminished by CDTA protonation. While the convention is to assign either a disjunctive

  9. Physical properties of the Creutzfeldt-Jakob disease agent

    Energy Technology Data Exchange (ETDEWEB)

    Sklaviadis, T.K.; Manuelidis, L.; Manuelidis, E.E.

    1989-03-01

    In this report, the authors present the first physical characterization of the Creutzfeld-Jakob disease agent. Preparations with high yields of infectivity (assayed infectious units) were obtained by a novel, gentle procedure in which initially sedimenting Gp34 (prion protein) was disaggregated by a variety of criteria with no subsequent loss of infectivity. Studies with this preparation indicate that most of the Creutzfeldt-Jakob disease agent has both a viruslike size and density. In velocity sedimentation and isopycnic sucrose gradients, infectivity comigrated with nucleic acid-protein complexes of appreciable size.

  10. Physical properties of the Creutzfeldt-Jakob disease agent

    International Nuclear Information System (INIS)

    Sklaviadis, T.K.; Manuelidis, L.; Manuelidis, E.E.

    1989-01-01

    In this report, the authors present the first physical characterization of the Creutzfeld-Jakob disease agent. Preparations with high yields of infectivity (assayed infectious units) were obtained by a novel, gentle procedure in which initially sedimenting Gp34 (prion protein) was disaggregated by a variety of criteria with no subsequent loss of infectivity. Studies with this preparation indicate that most of the Creutzfeldt-Jakob disease agent has both a viruslike size and density. In velocity sedimentation and isopycnic sucrose gradients, infectivity comigrated with nucleic acid-protein complexes of appreciable size

  11. Production of 5-hydroxy-7-methoxy-4-methylphthalide in a culture of Penicillium crustosum

    Directory of Open Access Journals (Sweden)

    Angela M.M.P. Valente

    Full Text Available The chemical reactions carried out by microorganisms have been used as a tool in modern chemistry. This paper reports the production of mycophenolic acid and a new phthalide by the endophytic fungus Penicillium crustosum obtained from coffee seeds. The fungus was cultivated in a liquid medium for a period of seven days and after that the culture medium was divided into four treatments: A, B, C and D, to which different organic substances were added. Treatment A was maintained as the control to evaluate the occurrence of biotransformation. Organic acids were added to the culture media of treatments B (ferulic and quinic acids and C [cinnamic and 3,4-(methylenedioxy cinnamic acids], and caffeine was added in the treatment D. All these organic compounds were dissolved in DMSO, and the fermentation was maintained for more 13 days, totalizing 20 days. Mycophenolic acid was isolated from the culture with no added acids (treatment A. Mycophenolic acid and a new phthalide, 5-hydroxy-7-methoxy-4-methylphthalide were isolated from treatments B and C, and mycophenolic acid and caffeine (added to the culture medium were isolated from treatment D. The structures were determined by NMR techniques and confirmed by MS and MS/MS techniques.As reações químicas realizadas por microorganismos têm sido utilizadas como uma ferramenta na química moderna. Este artigo relata a produção de ácido micofenólico e uma nova ftalida pelo fungo endofítico Penicillium crustosum obtido a partir de grãos de café. O fungo foi cultivado em meio líquido durante um período de sete dias, e depois disso, o meio de cultura foi dividido em quatro lotes: A, B, C e D, nos quais diferentes substâncias orgânicas foram adicionadas. O lote A foi mantido como controle para avaliar a ocorrência de biotransformação. Os ácidos orgânicos foram adicionados ao meio de cultura dos lotes B (ácidos ferúlico e quínico e C [ácido cinâmico e 3,4-(metilenodioxi cinâmico], e cafe

  12. In situ generation of silver nanoparticles in poly(vinyl alcohol)/poly(acrylic acid) polymer membranes in the absence of reducing agent and their effect on pervaporation of a water/acetic acid mixture

    International Nuclear Information System (INIS)

    Chaudhard, Shvshankar; Kwon, Yong Sung; Moon, MyungJun; Shon, Min Young; Park, You In; Nam, Seung Eun

    2016-01-01

    The in situ generation of silver nanoparticles in a poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) polymer matrix in the absence of any additional reducing agent is reported and tends to the membrane fabrication using solution-casting. Its effect on the separation of a water/acetic acid mixture by pervaporation is described. The results of UV spectroscopy, scanning electron microscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy analyses showed that the silver nanoparticles were successfully prepared and well dispersed in the polymer matrix. The increased hydrophilicity of the PVA/PAA membrane due to the presence of silver nanoparticles was confirmed by Fourier transform infrared spectroscopy, contact angle measurements, and membrane absorption studies. Pervaporation data for composite membranes showed a three-fold increase in the flux value, while the initially decreased separation factor subsequently showed a constant value. Overall, the pervaporation data suggested that the presence of silver nanoparticles benefited the dehydration process

  13. In situ generation of silver nanoparticles in poly(vinyl alcohol)/poly(acrylic acid) polymer membranes in the absence of reducing agent and their effect on pervaporation of a water/acetic acid mixture

    Energy Technology Data Exchange (ETDEWEB)

    Chaudhard, Shvshankar; Kwon, Yong Sung; Moon, MyungJun; Shon, Min Young [Dept. of Industrial Chemistry, Pukyong National University, Busan (Korea, Republic of); Park, You In; Nam, Seung Eun [Center for membranes, Korea Research Institute of Chemical Technology, Daejeon (Korea, Republic of)

    2016-12-15

    The in situ generation of silver nanoparticles in a poly(vinyl alcohol)/poly(acrylic acid) (PVA/PAA) polymer matrix in the absence of any additional reducing agent is reported and tends to the membrane fabrication using solution-casting. Its effect on the separation of a water/acetic acid mixture by pervaporation is described. The results of UV spectroscopy, scanning electron microscopy, and scanning electron microscopy/energy-dispersive X-ray spectroscopy analyses showed that the silver nanoparticles were successfully prepared and well dispersed in the polymer matrix. The increased hydrophilicity of the PVA/PAA membrane due to the presence of silver nanoparticles was confirmed by Fourier transform infrared spectroscopy, contact angle measurements, and membrane absorption studies. Pervaporation data for composite membranes showed a three-fold increase in the flux value, while the initially decreased separation factor subsequently showed a constant value. Overall, the pervaporation data suggested that the presence of silver nanoparticles benefited the dehydration process.

  14. Resistance of bacterial biofilms formed on stainless steel surface to disinfecting agent.

    Science.gov (United States)

    Królasik, Joanna; Zakowska, Zofia; Krepska, Milena; Klimek, Leszek

    2010-01-01

    The natural ability of microorganisms for adhesion and biofilm formation on various surfaces is one of the factors causing the inefficiency of a disinfection agent, despite its proven activity in vitro. The aim of the study was to determine the effectiveness of disinfecting substances on bacterial biofilms formed on stainless steel surface. A universally applied disinfecting agent was used in the tests. Bacterial strains: Listeria innocua, Pseudomonas putida, Micrococcus luteus, Staphylococcus hominis strains, were isolated from food contact surfaces, after a cleaning and disinfection process. The disinfecting agent was a commercially available acid specimen based on hydrogen peroxide and peroxyacetic acid, the substance that was designed for food industry usage. Model tests were carried out on biofilm formed on stainless steel (type 304, no 4 finish). Biofilms were recorded by electron scanning microscope. The disinfecting agent in usable concentration, 0.5% and during 10 minutes was ineffective for biofilms. The reduction of cells in biofilms was only 1-2 logarithmic cycles. The use of the agent in higher concentration--1% for 30 minutes caused reduction of cell number by around 5 logarithmic cycles only in the case of one microorganism, M. luteus. For other types: L. innocua, P. putida, S. hominis, the requirements placed on disinfecting agents were not fulfilled. The results of experiments proved that bacterial biofilms are resistant to the disinfectant applied in its operational parameters. Disinfecting effectiveness was achieved after twofold increase of the agent's concentration.

  15. Panel-reactive antibody levels and renal transplantation rates in sensitized patients after desensitization and human leucocyte antigen amino acid residue matching.

    Science.gov (United States)

    Shang, Wenjun; Dong, Laidong; Feng, Guiwen; Wang, Yue; Pang, Xinlu; Li, Jinfeng; Liu, Lei; Zhang, Weihong

    2013-08-01

    To determine whether a new desensitization protocol (mycophenolate mofetil [MMF], plasmapheresis and antithymocyte globulin [ATG], complemented with human leucocyte antigen [HLA] amino acid residue matching) could reduce panel-reactive antibody (PRA) levels in sensitized patients, to facilitate successful renal transplantation. Patients awaiting transplantation with PRA levels >10% received treatment with MMF; those with PRA levels >30% were also treated with plasmapheresis. Patients whose PRA level was desensitization were eligible for transplantation. When a donor became available, traditional HLA matching and HLA amino acid residue matching were performed. All patients received ATG induction therapy postoperatively. Thirty-two sensitized patients were enrolled. Desensitization produced a significant decrease in PRA levels; 27 patients (84.4%) became eligible for transplantation and 26 (81.2%) subsequently underwent successful transplantation. Residue matching improved the proportion with a mismatch number of 0-1 from 7.7% to 65.4%, compared with traditional HLA matching. Postoperatively, all patients showed immediate graft function. Acute rejection occurred in three patients (11.5%) and infections in seven patients (25.9%); all were treated successfully. The combination of a desensitization protocol (MMF, plasmapheresis and ATG) and residue matching appears to be an effective strategy for sensitized patients awaiting renal transplantation.

  16. Pyrogenicity of polyadenylic.polyuridylic acid in rabbits.

    Science.gov (United States)

    Won, S J; Lin, M T

    1991-05-01

    Polyadenylic.polyuridylic acid injected intravenously into rabbits produced a rapid-onset, monophasic fever. Pyrogenic tolerance occurred in rabbits following daily injections of polyadenylic.polyuridylic acid. However, direct injection of the agent into the preoptic anterior hypothalamic region of rabbit's brain produced a markedly different fever. After an intrahypothalamic injection of polyadenylic.polyuridylic acid, fever was delayed in onset and persisted for a longer period. At room temperature, the fever was due to both increased metabolism and cutaneous vasoconstriction. In a colder atmosphere the fever was due solely to increased metabolism, whereas in the heat the fever was due to reduction in cutaneous blood flow and respiratory evaporative heat loss. In addition, the fever induced by intravenous polyadenylic.polyuridylic acid injection was reversed by a cyclooxygenase inhibitor, but not by a protein synthesis inhibitor. Polyadenylic.polyuridylic acid was shown to stimulate PGE2 production from rabbit's hypothalamus in vitro. The results reveal that this agent is a prostaglandin-dependent pyrogen.

  17. In vitro interactions of amantadine hydrochloride, R-(-)-deprenyl hydrochloride and valproic acid sodium salt with antifungal agents against filamentous fungal species causing central nervous system infection.

    Science.gov (United States)

    Galgóczy, L; Tóth, Liliána; Virágh, M; Papp, T; Vágvölgyi, C S

    2012-12-01

    The mortality rates of fungal infections that affect the central nervous system are high in consequence of the absence of effective antifungal drugs with good penetration across the blood-brain barrier and the blood-cerebrospinal fluid barrier. In the present work in vitro antifungal activities of three good penetrating non-antifungal drugs (amantadine hydrochloride, R-(-)-deprenyl hydrochloride, valproic acid sodium salt) and their combinations with three antifungal agents (amphotericin B, itraconazole, terbinafine) were tested with broth microdilution method against eight fungal isolates belonging to Zygomycetes (Lichtheimia corymbifera, Rhizomucor miehei, Rhizopus microsporus var. rhizopodiformis, Saksenaeavasiformis) and Aspergillus genus (A. flavus, A. fumigatus, A. nidulans, A. terreus). These are known to be possible agents of central nervous fungal infections (CNFI). When used alone, the investigated nonantifungal drugs exerted slight antifungal effects. In their combinations with antifungal agents they acted antagonistically, additively and synergistically against zygomyceteous isolates. Primarily antagonistic interactions were revealed between the investigated drugs in case of Aspergilli, but additive and synergistic interactions were also observed. The additive and synergistic combinations allowed the usage of reduced concentrations of antifungal agents to inhibit the fungal growth in our study. These combinations would be a basis of an effective, less toxic therapy for treatment of CNFI.

  18. Study on the utilization of a sodium-sulfuric acid solution for the uranium minerals' leaching

    International Nuclear Information System (INIS)

    Echenique, Patricia; Fruchtenicht, Fernando; Gil, Daniel; Vigo, Daniel; Bouza, Angel; Vert, Gabriela; Becquart, Elena

    1988-01-01

    Argentine uranium minerals have been leached at bench scale with a different agent trying to reduce sulfuric acid consumption. The leaching agent was a sodium sulfate-sulfuric acid solution and the ore was from Sierra Pintada (San Rafael - Mendoza). The work was performed in stirred vessel at atmospheric pressure. The influence of different variables, pH, temperature, oxidant agent, sodium sulfate concentration and time, in the sulfuric acid consumption and the uranium yield was studied. (Author) [es

  19. The use of contrast agents in cardiac MRI

    International Nuclear Information System (INIS)

    Maurer, A.H.; Osbakken, M.

    1988-01-01

    Inherent NMR phenomena such as T/sub 1/ and T/sub 2/, and proton density can be used to provide tissue contrast on MR images. However, there are times when this contrast is not sufficient or does not provide tissue characterization data sufficient for use in definition of a pathophysiological insult. In this later case, paramagnetic agents might be of use in enhancement of relaxation time differences in one tissue or one portion of a tissue compared to another. Although several agents have been evaluated in this regard, most have been found inadequate because of their tissue toxicity. At present, gadolinium diethylenetriamine pentaacetric acid (Gd-DTPA) (which is an agent used in nuclear medicine studies) appears to be a good agent to use to distinguish normal from ischemic tissue. This agent has been used by a number of investigators to evaluate myocardial ischemia and provides images with better sensitivity and specificity for ischemia than imaging techniques using natural tissue contrast based on T/sub 1/ and T/sub 2/ differences

  20. Yeast Interacting Proteins Database: YNL189W, YHR216W [Yeast Interacting Proteins Database

    Lifescience Database Archive (English)

    Full Text Available g, expression is repressed by nutrient limitation Rows with this prey as prey (1) Rows with this prey as bai...osynthesis, expression is induced by mycophenolic acid resulting in resistance to the drug, expression is repressed by nutrient limit...ation Rows with this prey as prey Rows with this prey as

  1. Potassium fulvate as co-interpenetrating agent during graft polymerization of acrylic acid from cellulose.

    Science.gov (United States)

    Ghazy, Mohamed B M; El-Hai, Farag Abd; Mohamed, Magdy F; Essawy, Hisham A

    2016-10-01

    Grafting polymerization of acrylic acid onto cellulose in presence of potassium fulvate (KF) as a co-interpenetrating agent results enhanced water sorption compared to materials prepared similarly in its absence. The insertion of potassium fulvate (KF) did not affect the grafting process and is thought to proceed in parallel to the graft polymerization via intensive polycondensation reactions of its function groups (-COOH and OH) with COOH of the monomer and OH groups of cellulose. The combination of graft copolymerization and polycondensation reactions is assumed to produce interpenetrating network structure. Fourier transform infrared (FTIR) confirmed successful incorporation within the network structure which is an evidence for formation of interpenetrating network. The obtained structures showed homogeneous uniform surface as revealed by scanning electron microscopy (SEM). The obtained superabsorbent possessed high water absorbency 422 and 48.8g/g in distilled water and saline (0.9wt.% NaCl solution), respectively, and enhanced water retention even at elevated temperatures as revealed by thermogravimetric analysis (TGA). This could be explained by the high content of hydrophilic groups. The new superabsorbents proved to be efficient devices for controlled release of fertilizers which expands their use in agricultural applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Effect of some addition agents on the electrodeposition of cadmium from acidic chloride baths

    International Nuclear Information System (INIS)

    Abd El-Halim, A.M.; Baghlaf, A.O.; Sobahi, M.I.

    1984-01-01

    A further development of a chloride-based cadmium plating bath containing 0.3 M CdCl 2 .(5/2)H 2 O, 0.1 M HCl, 0.4 M H 3 BO 3 and 2.0 M NH 4 Cl (bath I) is described. The influences of the individual addition agents thiourea, coumarin Ni 2+ ions and I - ions on the characteristics of cadmium electrodeposition from acidic chloride electrolytes containing 0.3 M CdCl 2 .(5/2)H 2 O, 0.1 M HCl, 0.4 M H 3 BO 3 , 2.0 M NH 4 Cl, 0.5 M sodium potassium tartrate and 5 g gelatin l -1 (bath II) were studied. Bath II including a combination of the four above-mentioned additives was denoted bath III. The additive-containing bath III produced a brighter but less hard cadmium deposit than the additive-free bath II. The individual effects of melamine, 3-methyl-4-p-methoxyphenylazopyrazol-5-one, dimethylformamide (DMF) and DMF with biacetyl-bis-(benzoylhydrazone) on the cathodic polarization and current efficiency of cadmium electrodeposition from baths II and III, as well as on the morphology and microhardness of the as-plated cadmium deposits, were investigated and discussed. (Auth.)

  3. Antibiofilm Properties of Acetic Acid

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Morten; Jensen, Peter Østrup

    2014-01-01

    Bacterial biofilms are known to be extremely tolerant toward antibiotics and other antimicrobial agents. These biofilms cause the persistence of chronic infections. Since antibiotics rarely resolve these infections, the only effective treatment of chronic infections is surgical removal of the inf......Bacterial biofilms are known to be extremely tolerant toward antibiotics and other antimicrobial agents. These biofilms cause the persistence of chronic infections. Since antibiotics rarely resolve these infections, the only effective treatment of chronic infections is surgical removal...... of the infected implant, tissue, or organ and thereby the biofilm. Acetic acid is known for its antimicrobial effect on bacteria in general, but has never been thoroughly tested for its efficacy against bacterial biofilms. In this article, we describe complete eradication of both Gram-positive and Gram......-negative biofilms using acetic acid both as a liquid and as a dry salt. In addition, we present our clinical experience of acetic acid treatment of chronic wounds. In conclusion, we here present the first comprehensive in vitro and in vivo testing of acetic acid against bacterial biofilms....

  4. Synthesis of new polyphosphonic acids, uranium extracting agents in a phosphoric medium

    International Nuclear Information System (INIS)

    Pensec, T.

    1981-04-01

    Synthesis of organic phosphorus compounds for liquid-liquid extraction of traces of uranium in concentrated phosphoric acid is studied in view of industrial applications. Diphosphonic acids and monoesters and also triphosphonic acids and related compounds are synthetized. Extraction tests show a better efficiency than OPPA [fr

  5. Exo-metabolites of mycelial fungi isolated in production premises of cheese-making and meat-processing plants.

    Science.gov (United States)

    Kozlovsky, A G; Zhelifonova, V P; Antipova, T V; Baskunov, B P; Ivanushkina, N E; Ozerskaya, S M

    2014-01-01

    Data were obtained on the species composition of mycelial fungi isolated from the air of workrooms and production premises in cheese-making and meat-processing plants. The strains studied were shown to be capable of producing various low molecular weight compounds. Many of them are mycotoxins such as α-cyclopiazonic acid (CPA), mycophenolic acid (MPA), citrinin, cladosporin, roquefortine and ergot alkaloids. The profiles of the secondary metabolites were used to elucidate the species' names of the isolated strains.

  6. Contrast agents for tumor diagnosis in magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Rensuke; Doi, Hisayoshi; Okada, Shoji [University of Shizuoka (Japan). School of Pharmaceutical Science; Yano, Masayuki; Katano, Susumu; Nakajima, Nobuaki

    1992-01-01

    In order to develop contrast agents for tumor diagnosis in magnetic resonance imaging (MRI), we investigated the effects of several gadolinium complexes on T{sub 1} relaxation time of proton in some tissues of Ehrlich solid tumor-bearing mice. L-Aspartic acid, L-glutamic acid, DL-homocysteine, L-glutamyl-glutamic acid, glutathione, sperimidine and ethylenediaminetetrakis (methylenephosphate) (EDTMP) were used as ligands for Gd{sup 3+}. Since each Gd-complex could not be purified except Gd-EDTMP, the mixture of GdCl{sub 3} and a ligand was administered intravenously. Among the compounds tested, the mixture of aspartic acid, glutathione or spermidine with GdCl{sub 3} showed almost the same or above reduction of T{sub 1} relaxation times in the tumor tissue compared with Gd-diethylenetriamine pentaacetic acid (Gd-DTPA) which is used clinically. Furthermore, the contrast-enhancing effect of the three mixtures in the tumor was observed by in vivo T{sub 1}-weighted magnetic resonance imaging. The in vivo tissue distribution using radioactive {sup 153}Gd{sup 3+} showed that these mixtures mentioned above were also taken up more highly in the tumor than {sup 153}GdCl{sub 3} itself and {sup 153}Gd-DTPA, suggesting the formation of Gd-complexes. However, the overall tissue distribution of the mixtures was similar to that of {sup 153}GdCl{sub 3} because the Gd-complexes were not purified. Gd-EDTMP exhibited the almost same effects with Gd-DTPA as a contrast agent. (author).

  7. The Influenced of Salting Out Agent of Phosphat Ion and Ferrosulfamic in Extraction of Thorium and Uranium

    International Nuclear Information System (INIS)

    Busron Masduki; Didiek Herhady, R.

    2002-01-01

    It was carried out thorium-uranium extraction using one stage mixer settler to investigate the influenced of salting out agent of nitric acid and nitric aluminium. The result of this experiment showed the salting out of agent for nitric aluminium of 0.5 M much more significantly increase the distribution coefficient of uranium, but not for the thorium. The distribution coefficient of thorium much more significantly increased after nitric aluminium addition ≥1.0 M. There was not any meaningly differences the waste volume between nitric acid and nitric aluminium in its utilization. Reductor agent of ion Fe 2+ for chromi and decontaminate agent for protactinium in feed extraction, did not any influences of thorium and uranium distribution coefficient. (author)

  8. Multitarget Molecular Hybrids of Cinnamic Acids

    Directory of Open Access Journals (Sweden)

    Aikaterini Peperidou

    2014-12-01

    Full Text Available In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids—2e, 2a, 2g—and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX inhibition and analgesic activity (IC50 = 0.34 μΜ and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 μΜ and the highest anti-proteolytic activity (IC50= 5 μΜ. The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91% and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure–activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding.

  9. Stress -induced biosynthesis of dicaffeoylquinic acids in globe artichoke

    NARCIS (Netherlands)

    Moglia, A.; Lanteri, S.; Comino, C.; Acquadro, A.; Vos, de C.H.; Beekwilder, M.J.

    2008-01-01

    Leaf extracts from globe artichoke (Cynara cardunculus L. var. scolymus) have been widely used in medicine as hepatoprotectant and choleretic agents. Globe artichoke leaves represent a natural source of phenolic acids with dicaffeoylquinic acids, such as cynarin (1,3-dicaffeoylquinic acid), along

  10. The ORION study: comparison of two sirolimus-based regimens versus tacrolimus and mycophenolate mofetil in renal allograft recipients.

    Science.gov (United States)

    Flechner, S M; Glyda, M; Cockfield, S; Grinyó, J; Legendre, Ch; Russ, G; Steinberg, S; Wissing, K M; Tai, S S

    2011-08-01

    Safety and efficacy of two sirolimus (SRL)-based regimens were compared with tacrolimus (TAC) and mycophenolate mofetil (MMF). Renal transplantation recipients were randomized to Group 1 (SRL+TAC; week 13 TAC elimination [n = 152]), Group 2 (SRL + MMF [n = 152]) or Group 3 (TAC + MMF [n = 139]). Group 2, with higher-than-expected biopsy-confirmed acute rejections (BCARs), was sponsor-terminated; therefore, Group 2 two-year data were limited. At 1 and 2 years, respectively, graft (Group 1: 92.8%, 88.5%; Group 2: 90.6%, 89.9%; Group 3: 96.2%, 95.4%) and patient (Group 1: 97.3%, 94.4%; Group 2: 95.2%, 94.5%; Group 3: 97.0%, 97.0%) survival rates were similar. One- and 2-year BCAR incidence was: Group 1, 15.2%, 17.4%; Group 2, 31.3%, 32.8%; Group 3, 8.2%, 12.3% (Group 2 vs. 3, p < 0.001). Mean 1- and 2-year modified intent-to-treat glomerular filtration rates (mL/min) were similar. Primary reason for discontinuation was adverse events (Group 1, 34.2%; Group 2, 33.6%; Group 3, 22.3%; p < 0.05). In Groups 1 and 2, delayed wound healing and hyperlipidemia were more frequent. One-year post hoc analysis of new-onset diabetes posttransplantation was greater in TAC recipients (Groups 1 and 3 vs. 2, 17% vs. 6%; p = 0.004). Between-group malignancy rates were similar. The SRL-based regimens were not associated with improved outcomes for kidney transplantation patients. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. Root Conditioning and Agents Effect in Regeneration of Periodontal Tissue

    Directory of Open Access Journals (Sweden)

    Kadkhoda Z

    1999-12-01

    Full Text Available Periodontitis affected root surfaces are hypermineralized and contaminated with cytotoxic and"nother biologically active substances."nThe instrumented surface will inervitably be coverd by a smear layer following root planing with or without flap."nSmear layer is resistant to saline rinsing, but may be removed with agents such as acids (e.g.citric acid, tetracyclines, EDTA, and laser."nLow pH aqueous solutions such as citric acid have been used in surgical periodontal therapy mainly for two reasons, It dissolves smear layer after a relatively short exposure time and it has been claimed to selectively remove root surface associated mineral exposing collagen to varying degrees. A root surface coated with collagen appears to be a preferred surface for fibroblast attachment, a cellular event fundamental to successful periodontal wound healing."nSeveral studies indicate the potential of tetracycline (TTE-HCL in periodontal regeneration. Its acidic pH suggest that it can be used as a demineralization agent and removing the smear layer and exposing collagen matrix of the dentin."nChalating agent (EDTA working at neutral pH appears preferable with respect to preserving the integrity of exposed collagen fibers, early colonization, and wound healing. In addition, etching at neutral pH has been reported preserve adjacent tissue- vitality, while etching at low pH necrotizes the fiap and adjacent periodontium."nClinical and subclinical studies have demonstrated laser waves can remove calculus and bacterial plaque and pocket epithelium and strile the root surface and can expose the dentin collagen and dentinal tublules, and leads to pronounce reducing of probing depth around teeth diseased with periodontitis.

  12. In vitro, in silico and in vivo studies of ursolic acid as an anti-filarial agent.

    Directory of Open Access Journals (Sweden)

    Komal Kalani

    Full Text Available As part of our drug discovery program for anti-filarial agents from Indian medicinal plants, leaves of Eucalyptus tereticornis were chemically investigated, which resulted in the isolation and characterization of an anti-filarial agent, ursolic acid (UA as a major constituent. Antifilarial activity of UA against the human lymphatic filarial parasite Brugia malayi using in vitro and in vivo assays, and in silico docking search on glutathione-s-transferase (GST parasitic enzyme were carried out. The UA was lethal to microfilariae (mf; LC100: 50; IC50: 8.84 µM and female adult worms (LC100: 100; IC50: 35.36 µM as observed by motility assay; it exerted 86% inhibition in MTT reduction potential of the adult parasites. The selectivity index (SI of UA for the parasites was found safe. This was supported by the molecular docking studies, which showed adequate docking (LibDock scores for UA (-8.6 with respect to the standard antifilarial drugs, ivermectin (IVM -8.4 and diethylcarbamazine (DEC-C -4.6 on glutathione-s-transferase enzyme. Further, in silico pharmacokinetic and drug-likeness studies showed that UA possesses drug-like properties. Furthermore, UA was evaluated in vivo in B. malayi-M. coucha model (natural infection, which showed 54% macrofilaricidal activity, 56% female worm sterility and almost unchanged microfilaraemia maintained throughout observation period with no adverse effect on the host. Thus, in conclusion in vitro, in silico and in vivo results indicate that UA is a promising, inexpensive, widely available natural lead, which can be designed and developed into a macrofilaricidal drug. To the best of our knowledge this is the first ever report on the anti-filarial potential of UA from E. tereticornis, which is in full agreement with the Thomson Reuter's 'Metadrug' tool screening predictions.

  13. Iron removal on feldspar by using Averrhoa bilimbii as bioleaching agent

    Science.gov (United States)

    Amin, Muhammad; Aji, Bramantyo B.; Supriyatna, Yayat Iman; Bahfie, Fathan

    2017-01-01

    Investigation of Averrhoa bilimbii as bioleaching agent was carried out. Parameters of leaching duration, acid concentration, and temperature were performed in iron removal process. Feldspar with sized 149 µm was diluted in 30 ml acid solution in order to reduce its iron content. The experimental results showed a good technical feasibility of the process which iron oxide content of feldspar was decreased from 2.24% to 0.29%. The lowest iron concentration remained was obtained after 5 hours of leaching treatment at 60 °C, and concentrated (100 vol%) Averrhoa bilimbii extract as bioleaching agent. SEM characterizations were carried out on the feldspar before and after the leaching treatment. The result shows that there were no significant effect of leaching process on the ore morphology.

  14. High-level production of C-11-carboxyl-labeled amino acids

    International Nuclear Information System (INIS)

    Washburn, L.C.; Sun, T.T.; Byrd, B.L.; Hayes, R.L.; Butler, T.A.; Callahan, A.P.

    1979-01-01

    Carbon-11-labeled amino acids have significant potential as agents for positron tomographic functional imaging. We have developed a rapid, high-temperature, high-pressure modification of the Buecherer--Strecker amino acid synthesis and found it to be quite general for the production of C-11-carboxyl-labeled neutral amino acids. Production of C-11-carboxyl-labeled DL-tryptophan requires certain modifications in the procedure. Twelve different amino acids have been produced to date by this technique. Synthesis and chromatographic purification require approximately 40 min, and C-11-carboxyl-labeled amino acids have been produced in yields of up to 425 mCi. Two C-11-carboxyl-labeled amino acids are being investigated clinically for tumor scanning and two others for pancreatic imaging. Over 120 batches of the various agents have been produced for clinical use over a three-year period

  15. Comparison of crystal and solution hemoglobin binding of selected antigelling agents and allosteric modifiers

    International Nuclear Information System (INIS)

    Mehanna, A.S.; Abraham, D.J.

    1990-01-01

    This paper details comprehensive binding studies (solution and X-ray) of human hemoglobin A with a group of halogenated carboxylic acids that were investigated as potential antisickling agents. It is, to our knowledge, the first study to compare solution and crystal binding for a series of compounds under similar high-salt conditions used for cocrystallization. The compounds include [(3,4-dichlorobenzyl)oxy]acetic acid, [(p-bromobenzyl)oxy]acetic acid, clofibric acid, and bezafibrate. The location and stereochemistry of binding sites have been established by X-ray crystallography, while the number of binding sites and affinity constants were measured by using equilibrium dialysis. The observed crystal structures are consistent with the binding observed in solution and that the number of binding sites is independent of salt concentration, while the binding constant increases with increasing salt concentration. The studies also reveal that relatively small changes in the chemical structure of a drug molecule can result in entirely different binding sites on the protein. Moreover, the X-ray studies provide a possible explanation for the multiplicity in function exhibited by these compounds as allosteric modulators and/or antisickling agents. Finally, the studies indicate that these compounds bind differently to the R and T states of hemoglobin, and observation of special significance to the original design of these agents

  16. Citric Acid Alternative to Nitric Acid Passivation

    Science.gov (United States)

    Lewis, Pattie L. (Compiler)

    2013-01-01

    The Ground Systems Development and Operations GSDO) Program at NASA John F. Kennedy Space Center (KSC) has the primary objective of modernizing and transforming the launch and range complex at KSC to benefit current and future NASA programs along with other emerging users. Described as the launch support and infrastructure modernization program in the NASA Authorization Act of 2010, the GSDO Program will develop and implement shared infrastructure and process improvements to provide more flexible, affordable, and responsive capabilities to a multi-user community. In support of the GSDO Program, the purpose of this project is to demonstratevalidate citric acid as a passivation agent for stainless steel. Successful completion of this project will result in citric acid being qualified for use as an environmentally preferable alternative to nitric acid for passivation of stainless steel alloys in NASA and DoD applications.

  17. Newly designed Tc(V)-99m dimercaptosuccinic acid: An agent of high accuracy for the diagnosis of head and neck and soft tissue tumors

    International Nuclear Information System (INIS)

    Endo, K.; Ohta, H.; Sakahara, H.; Nakashima, T.; Masuda, H.; Horiuchi, K.; Yokoyama, A.; Torizuka, K.

    1984-01-01

    Being aware of the ideal nuclear properties of Tc-99m, interest has been focused on the design of (+5) oxidation state Tc-99m dimercaptosuccinic acid (DMSA) as a tumor seeking agent. This Tc(V)-99m DMSA holding a TcO/sup 3-//sub 4/ core, alike PO/sup 3-//sub 4/, with competent characteristics for tumor uptake, had a different distribution behavior from the well-known renal scanning agent; Tc(III)-99m DMSA. Basic studies, carried out in vitro and in vivo with Ehrlich tumor cells or bearing mice, clearly substantiated its great potentiality for clinical use. Therefore, 193 untreated patients with histologically proven diagnosis (132 malignant and 61 benign tumors) were evaluated. In 53 primary head and neck tumor (mainly squamous cell carcinomas and plemorphic adenomas or abscess), its sensitivity and specificity was 78% and 87%, as opposed to Ga-67 citrate of 85% and 51% respectively. In 18 malignant soft tissue tumors, all but one (94%) showed significant uptake of Tc(V)-99m DMSA, while Ga-67 was positive in only 60% of these cases. The specificity of both agents was 74% and 86%, respectively. However in lung and abdominal tumors, lymphomas, melanomas and inflammatory lesions, the sensitivity was poor of less than 40%. Also negative were scans in most thyroid cancers, however, 5 patients with medullary thyroid cancers, were all positive with Tc(V)-99m DMSA and was useful follow patients after surgery. Thus, a different uptake mechanism for this agent could be visualized. The authors conclude that Tc(V)-99m DMSA provided a good basis for its clinical application as a tumor imaging agent, mainly in head and neck squamous cell carcinomas, medullary thyroid cancers and soft tissue tumors

  18. Mycophenolate

    Science.gov (United States)

    ... your muscles; confusion or difficulty thinking clearly; unsteadiness; memory loss; difficulty speaking or understanding what others say; ... is important to keep all medication out of sight and reach of children as many containers (such ...

  19. Instability of expanded simple tandem repeats is induced in cell culture by a variety of agents: N-Nitroso-N-ethylurea, benzo(a)pyrene, etoposide and okadaic acid

    Energy Technology Data Exchange (ETDEWEB)

    Polyzos, Aris [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada); Parfett, Craig [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada); Healy, Caroline [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada); Douglas, George R. [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada); Yauk, Carole L. [Environmental Health Centre, Environmental and occupational Toxicology Division, Health Canada, Tunney' s Pasture, P.L. 0803A, Ottawa, Ont., K1A 0L2 (Canada)]. E-mail: Carole_Yauk@hc-sc.gc.ca

    2006-06-25

    Expanded simple tandem repeat (ESTR) sequences have proven useful biomarkers to detect genotoxicity in vivo. Their high sensitivity has been used to assess environmentally relevant doses of mutagens such as ionizing radiation, DNA alkylating agents and airborne particulate pollution, for germline mutations in mouse assays. The mutagenic response involves size alteration of these ESTR loci induced by agents causing a variety of cellular damage. The mechanistic aspects of this induced instability remain unclear and have not been studied in detail. Mechanistic knowledge is important to help understand the relevance of increased ESTR mutation frequencies. In this study, we applied a murine cell culture system to examine induced response to four agents exhibiting different modes of toxic action including: N-nitroso-N-ethylurea (ENU), benzo(a)pyrene (BaP), okadaic acid and etoposide at slightly sub-toxic levels. We used single-molecule-polymerase chain reaction (SM-PCR) to assess the relative mutant frequency after 4-week chemical treatments at the Ms6-hm ESTR sequence of cultured C3H/10T1/2 cells (a mouse embryonic cell line). Increased mutation was observed with both 0.64 mM ENU (1.95-fold increase, P < 0.0001), 1 {mu}M benzo(a)pyrene (1.87-fold increase, P = 0.0006) and 3 nM etoposide (1.89-fold increase, P = 0.0003). The putative ESTR mutagen okadaic acid (1.27-fold increase, P = 0.2289), administered at 0.5 nM, did not affect the C3H/10T1/2 Ms6-hm locus. Therefore, agents inducing small and bulky adducts, and indirectly causing strand breaks through inhibition of topoisomerase, caused similar induction of instability at an ESTR locus at matched toxicities. As size spectra for induced mutations were identical, the data indicate that although these chemicals exhibit distinct modes of action, a similar indirect process is influencing ESTR instability. In contrast, a potent tumour promoter that is a kinase inhibitor does not contribute to induced ESTR instability in

  20. Instability of expanded simple tandem repeats is induced in cell culture by a variety of agents: N-Nitroso-N-ethylurea, benzo(a)pyrene, etoposide and okadaic acid

    International Nuclear Information System (INIS)

    Polyzos, Aris; Parfett, Craig; Healy, Caroline; Douglas, George R.; Yauk, Carole L.

    2006-01-01

    Expanded simple tandem repeat (ESTR) sequences have proven useful biomarkers to detect genotoxicity in vivo. Their high sensitivity has been used to assess environmentally relevant doses of mutagens such as ionizing radiation, DNA alkylating agents and airborne particulate pollution, for germline mutations in mouse assays. The mutagenic response involves size alteration of these ESTR loci induced by agents causing a variety of cellular damage. The mechanistic aspects of this induced instability remain unclear and have not been studied in detail. Mechanistic knowledge is important to help understand the relevance of increased ESTR mutation frequencies. In this study, we applied a murine cell culture system to examine induced response to four agents exhibiting different modes of toxic action including: N-nitroso-N-ethylurea (ENU), benzo(a)pyrene (BaP), okadaic acid and etoposide at slightly sub-toxic levels. We used single-molecule-polymerase chain reaction (SM-PCR) to assess the relative mutant frequency after 4-week chemical treatments at the Ms6-hm ESTR sequence of cultured C3H/10T1/2 cells (a mouse embryonic cell line). Increased mutation was observed with both 0.64 mM ENU (1.95-fold increase, P < 0.0001), 1 μM benzo(a)pyrene (1.87-fold increase, P = 0.0006) and 3 nM etoposide (1.89-fold increase, P = 0.0003). The putative ESTR mutagen okadaic acid (1.27-fold increase, P = 0.2289), administered at 0.5 nM, did not affect the C3H/10T1/2 Ms6-hm locus. Therefore, agents inducing small and bulky adducts, and indirectly causing strand breaks through inhibition of topoisomerase, caused similar induction of instability at an ESTR locus at matched toxicities. As size spectra for induced mutations were identical, the data indicate that although these chemicals exhibit distinct modes of action, a similar indirect process is influencing ESTR instability. In contrast, a potent tumour promoter that is a kinase inhibitor does not contribute to induced ESTR instability in cell

  1. Sequestering agents for the removal of actinides from waste streams

    Energy Technology Data Exchange (ETDEWEB)

    Raymond, K.N.; White, D.J.; Xu, Jide; Mohs, T.R. [Univ. of California, Berkeley, CA (United States)

    1997-10-01

    The goal of this project is to take a biomimetic approach toward developing new separation technologies for the removal of radioactive elements from contaminated DOE sites. To achieve this objective, the authors are investigating the fundamental chemistry of naturally occurring, highly specific metal ion sequestering agents and developing them into liquid/liquid and solid supported actinide extraction agents. Nature produces sideophores (e.g., Enterobactin and Desferrioxamine B) to selectivity sequester Lewis acidic metal ions, in particular Fe(III), from its surroundings. These chelating agents typically use multiple catechols or hydroxamic acids to form polydentate ligands that chelate the metal ion forming very stable complexes. The authors are investigating and developing analogous molecules into selective chelators targeting actinide(IV) ions, which display similar properties to Fe(III). By taking advantage of differences in charge, preferred coordination number, and pH stability range, the transition from nature to actinide sequestering agents has been applied to the development of new and highly selective actinide extraction technologies. Additionally, the authors have shown that these chelating ligands are versatile ligands for chelating U(VI). In particular, they have been studying their coordination chemistry and fundamental interactions with the uranyl ion [UO{sub 2}]{sup 2+}, the dominant form of uranium found in aqueous media. With an understanding of this chemistry, and results obtained from in vivo uranium sequestration studies, it should be possible to apply these actinide(IV) extraction technologies to the development of new extraction agents for the removal of uranium from waste streams.

  2. [Effects of different neutralizing agents on succinate production by Actinobacillus succinogenes NJ113].

    Science.gov (United States)

    Yang, Zhuona; Jiang, Min; Li, Jian; Fang, Xiaojiang; Ye, Guizi; Bai, Xuefei; Zheng, Xiaoyu; Wei, Ping

    2010-11-01

    Different neutralizing agents were used as pH controller to investigate their effects on the growth and succinic acid production of Actinobacillus succinogenes NJ113. The fermentation results showed that Ca(OH)2, CaCO3 and NH4OH were not suitable for succinic acid production by A. succinogenes NJ113 because of their negative effects on cell growth. When Na-base was used, cells would flocculate and lump, and due to the sodium ion concentration reaching to a high level, OD660 dropped sharply after 12 h of fermentation. Mg-base was better because there was no significant inhibition by magnesium ion. Two combined neutralizing agents were used to maintain pH level, one with NaOH and Mg(OH)2 while the other with Na2CO3 and Mg(OH)2. The optimum ratios of the combined neutralizing agents were both 1:1 (g:g) when using 100 g/L glucose. When NaOH and Mg(OH)2 were chosen with the ratio of 1:1(g:g), 69.8 g/L of the succinic acid and 74.5% of the yield was obtained.

  3. Enhanced Peroxide Resistance of In Vitro Mutagenized Fluorideresistant Klebsiella pneumoniae Ureases for Catalytic Buffering of Agent Decontamination Reactions

    National Research Council Canada - National Science Library

    Fry, Ilona J; DeFrank, Joseph J

    2004-01-01

    ...) and oxidative surety agent decontamination technologies. Ammonia production from urea by urease neutralizes the production of Oalkylphosphonic acids resulting from the hydrolysis of Nerve agents such as Sarin and VX...

  4. Phenolic biotransformations during conversion of ferulic acid to vanillin by lactic acid bacteria.

    Science.gov (United States)

    Kaur, Baljinder; Chakraborty, Debkumar; Kumar, Balvir

    2013-01-01

    Vanillin is widely used as food additive and as a masking agent in various pharmaceutical formulations. Ferulic acid is an important precursor of vanillin that is available in abundance in cell walls of cereals like wheat, corn, and rice. Phenolic biotransformations can occur during growth of lactic acid bacteria (LAB), and their production can be made feasible using specialized LAB strains that have been reported to produce ferulic acid esterases. The present study aimed at screening a panel of LAB isolates for their ability to release phenolics from agrowaste materials like rice bran and their biotransformation to industrially important compounds such as ferulic acid, 4-ethyl phenol, vanillic acid, vanillin, and vanillyl alcohol. Bacterial isolates were evaluated using ferulic acid esterase, ferulic acid decarboxylase, and vanillin dehydrogenase assays. This work highlights the importance of lactic acid bacteria in phenolic biotransformations for the development of food grade flavours and additives.

  5. Phenolic Biotransformations during Conversion of Ferulic Acid to Vanillin by Lactic Acid Bacteria

    Science.gov (United States)

    Kaur, Baljinder; Kumar, Balvir

    2013-01-01

    Vanillin is widely used as food additive and as a masking agent in various pharmaceutical formulations. Ferulic acid is an important precursor of vanillin that is available in abundance in cell walls of cereals like wheat, corn, and rice. Phenolic biotransformations can occur during growth of lactic acid bacteria (LAB), and their production can be made feasible using specialized LAB strains that have been reported to produce ferulic acid esterases. The present study aimed at screening a panel of LAB isolates for their ability to release phenolics from agrowaste materials like rice bran and their biotransformation to industrially important compounds such as ferulic acid, 4-ethyl phenol, vanillic acid, vanillin, and vanillyl alcohol. Bacterial isolates were evaluated using ferulic acid esterase, ferulic acid decarboxylase, and vanillin dehydrogenase assays. This work highlights the importance of lactic acid bacteria in phenolic biotransformations for the development of food grade flavours and additives. PMID:24066293

  6. Studies on radiolysis of amino acids, (3)

    International Nuclear Information System (INIS)

    Oku, Tadatake

    1978-01-01

    For the purpose of investigating the radiolysis of amino acids and the safeness to radiation, the radiolytic mechanism and radio-sensitivity of sulfur-containing amino acids in aqueous solution in the presence of air or in the atmosphere of nitrogen were studied. Aqueous solutions of L-methionine, cysteine (both 1mM) and L-cystine (0.3mM) were irradiated with γ-ray of 60 Co at the dose of 4.2 - 2,640 x 10 3 rad. The amino acids and the radiolytic products were determined with an amino acid analyzer. The volatile sulfur compounds formed from γ-irradiated methionine were estimated by a flame photometric detector-gas chromatograph. From the results obtained, G values of the radiolysis of sulfur-containing amino acids and the products were calculated, and the radiolytic mechanisms of methionine, cysteine and cystine were proposed. The radio-sensitivity of sulfur-containing amino acids was shown as follows: cysteine (C3-SH) > methionine (C5, -SCH 3 ) > cystine (C 6 , -S-S-). Off-flavor development from γ-irradiated methionine when oxidizing agent was added was less than that when reducing agent was added. (Kobatake, H.)

  7. Citric acid as multifunctional agent in blowing films of starch/PBAT

    Directory of Open Access Journals (Sweden)

    Patrícia Salomão Garcia

    2011-09-01

    Full Text Available Citric acid was used as a compatibilizer in the production of starch and PBAT films plasticized with glycerol and processed by blow extrusion. Films produced were characterized by WVP, mechanical properties, FT-IR-ATR and SEM. WPV ranged from 3.71 to 12.73×10-11 g m-1 s-1 Pa-1, while tensile strength and elongation at break ranged from 1.81 to 7.15 MPa and from 8.61 to 23.63%, respectively. Increasing the citric acid concentration improved WVP and slightly decreased film resistance and elongation. The films micrographs revealed a more homogeneous material with the addition of citric acid. However, the infrared spectra revealed little about cross-linking esterification reaction

  8. The effect of salivary pH on diametral tensile strength of resin modified glass ionomer cement coated with coating agent

    Science.gov (United States)

    Ismayanti, D.; Triaminingsih, S.; Eriwati, Y. K.

    2017-08-01

    The aim of this study was to evaluate the effect of artificial saliva with different acidities on the diametral tensile strength of Resin Modified Glass Ionomer Cement (RMGIC) coated with varnish and nanofilled coating agent. The specimens coated with coating agents were immersed in artificial saliva with pH of 4.5, 5.5, and 7 for 24 hours in an incubatorat 37°C. The diametral tensile strength of the specimens was tested with Universal Testing Machine. There were no significant differences on the diametral tensile strength of all specimens that were put into groups based on the acidity of the saliva and the type of coating agent (p>0.05). Both varnish and nanofilled coating agent stayed on the RMGIC in the acidic condition that simulated the true condition of oral cavity in people with high caries risk for the 24 hours of maturation.

  9. Evaluation of pawpaw leaves extract as anti-corrosion agent for ...

    African Journals Online (AJOL)

    Pawpaw leaves extract was examined as anti-corrosion agent for aluminium in hydrochloric acid medium. The extract and corrosion product were analyzed using Fourier transform infrared spectrophotometer (FTIR). Thermometric, gravimetric, potentiodynamic polarization and scanning electron microscopic methods were ...

  10. Quantification of 4'-geranyloxyferulic acid, a new natural colon cancer chemopreventive agent, by HPLC-DAD in grapefruit skin extract.

    Science.gov (United States)

    Genovese, S; Epifano, F; Carlucci, G; Marcotullio, M C; Curini, M; Locatelli, M

    2010-10-10

    Oxyprenylated natural products (isopentenyloxy-, geranyloxy- and the less spread farnesyloxy-compounds and their biosynthetic derivatives) represent a family of secondary metabolites that have been consider for years merely as biosynthetic intermediates of the most abundant C-prenylated derivatives. Many of the isolated oxyprenylated natural products were shown to exert in vitro and in vivo remarkable anti-cancer and anti-inflammatory effects. 4'-Geranyloxyferulic acid [3-(4'-geranyloxy-3'-methoxyphenyl)-2-trans-propenoic] has been discovered as a valuable chemopreventive agent of several types of cancer. After development of a high yield and "eco-friendly" synthetic scheme of this secondary metabolite, starting from cheap and non-toxic reagents and substrates, we developed a new HPLC-DAD method for its quantification in grapefruit skin extract. A preliminary study on C18 column showed the separation between GOFA and boropinic acid (having the same core but with an isopentenyloxy side chain), used as internal standard. The tested column were thermostated at 28+/-1 degrees C and the separation was achieved in gradient condition at a flow rate of 1 mL/min with a starting mobile phase of H(2)O:methanol (40:60, v/v, 1% formic acid). The limit of detection (LOD, S/N=3) was 0.5 microg/mL and the limit of quantification (LOQ, S/N=10) was 1 microg/mL. Matrix-matched standard curves showed linearity up to 75 microg/mL. In the analytical range the precision (RSD%) values were extract of grapefruit. In conclusion, this method showed LOQ values able to selective quantification of this analyte in grapefruit skin extract.

  11. Characterization of radionuclide-chelating agent complexes found in low-level radioactive decontamination waste. Literature review

    International Nuclear Information System (INIS)

    Serne, R.J.; Felmy, A.R.; Cantrell, K.J.; Krupka, K.M.; Campbell, J.A.; Bolton, H. Jr.; Fredrickson, J.K.

    1996-03-01

    The US Nuclear Regulatory Commission is responsible for regulating the safe land disposal of low-level radioactive wastes that may contain organic chelating agents. Such agents include ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), picolinic acid, oxalic acid, and citric acid, and can form radionuclide-chelate complexes that may enhance the migration of radionuclides from disposal sites. Data from the available literature indicate that chelates can leach from solidified decontamination wastes in moderate concentration (1--100 ppm) and can potentially complex certain radionuclides in the leachates. In general it appears that both EDTA and DTPA have the potential to mobilize radionuclides from waste disposal sites because such chelates can leach in moderate concentration, form strong radionuclide-chelate complexes, and can be recalcitrant to biodegradation. It also appears that oxalic acid and citric acid will not greatly enhance the mobility of radionuclides from waste disposal sites because these chelates do not appear to leach in high concentration, tend to form relatively weak radionuclide-chelate complexes, and can be readily biodegraded. In the case of picolinic acid, insufficient data are available on adsorption, complexation of key radionuclides (such as the actinides), and biodegradation to make definitive predictions, although the available data indicate that picolinic acid can chelate certain radionuclides in the leachates

  12. Characterization of radionuclide-chelating agent complexes found in low-level radioactive decontamination waste. Literature review

    Energy Technology Data Exchange (ETDEWEB)

    Serne, R.J.; Felmy, A.R.; Cantrell, K.J.; Krupka, K.M.; Campbell, J.A.; Bolton, H. Jr.; Fredrickson, J.K. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-03-01

    The US Nuclear Regulatory Commission is responsible for regulating the safe land disposal of low-level radioactive wastes that may contain organic chelating agents. Such agents include ethylenediaminetetraacetic acid (EDTA), diethylenetriaminepentaacetic acid (DTPA), picolinic acid, oxalic acid, and citric acid, and can form radionuclide-chelate complexes that may enhance the migration of radionuclides from disposal sites. Data from the available literature indicate that chelates can leach from solidified decontamination wastes in moderate concentration (1--100 ppm) and can potentially complex certain radionuclides in the leachates. In general it appears that both EDTA and DTPA have the potential to mobilize radionuclides from waste disposal sites because such chelates can leach in moderate concentration, form strong radionuclide-chelate complexes, and can be recalcitrant to biodegradation. It also appears that oxalic acid and citric acid will not greatly enhance the mobility of radionuclides from waste disposal sites because these chelates do not appear to leach in high concentration, tend to form relatively weak radionuclide-chelate complexes, and can be readily biodegraded. In the case of picolinic acid, insufficient data are available on adsorption, complexation of key radionuclides (such as the actinides), and biodegradation to make definitive predictions, although the available data indicate that picolinic acid can chelate certain radionuclides in the leachates.

  13. Low molecular weight compounds as effective dispersing agents in the formation of colloidal silver nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Natsuki, Jun; Natsuki, Toshiaki, E-mail: natsuki@shinshu-u.ac.jp; Abe, Takao [Shinshu University, Faculty of Textile Science and Technology (Japan)

    2013-03-15

    A convenient method to synthesize uniform, well-dispersed colloidal silver nanoparticles is described. Aldonic acid or {alpha}-hydroxy acid compounds of low molecular weight are used instead of polymeric compounds as dispersing agents to prepare silver nanoparticles. The size, conformation, and electrical conductivity of the silver nanoparticles, and the effect and function of the dispersing agents are investigated in detail. Using these low molecular weight compounds as dispersing agents, silver nanoparticles with a diameter of 10 nm or less and high electrical conductivity can be obtained. In addition, this procedure allows silver nanoparticles to be sintered at 150 Degree-Sign C, which is lower than that required for silver nanoparticle formulation using polymeric compounds (200 Degree-Sign C). The silver nanoparticles produced by this process can be used to prepare various inks and to manufacture electronic circuits. It is found that low molecular weight compounds are more effective dispersing agents than polymeric compounds in the formation of silver nanoparticles.

  14. Treatment of neuro-ophthalmic sarcoidosis.

    Science.gov (United States)

    Frohman, Larry P

    2015-03-01

    Because of the rarity of neuro-ophthalmic sarcoidosis, there are no therapeutic guidelines based on evidence-based medicine for this disorder. Review of literature combined with personal experience. Corticosteroids are the preferred initial therapy for neuro-ophthalmic sarcoidosis. If patients cannot tolerate the requisite dose of corticosteroid needed to control their disease, or if corticosteroids fail to adequately control the disease process, the choices of a second agent are based on the consideration of rapidity of clinical response and the safety profile. Although methotrexate and mycophenolate mofetil are the medications that are often selected after corticosteroid failure, more rapidly acting agents that have been used are infliximab and intravenous cyclophosphamide.

  15. Thymoglobulin induction in liver transplant recipients with a tacrolimus, mycophenolate mofetil, and steroid immunosuppressive regimen: a five-year randomized prospective study.

    Science.gov (United States)

    Boillot, Olivier; Seket, Belhassen; Dumortier, Jérôme; Pittau, Gabriella; Boucaud, Catherine; Bouffard, Yves; Scoazec, Jean-Yves

    2009-11-01

    This randomized, comparative study assessed the long-term efficacy and tolerability of thymoglobulin (TMG) induction in 93 liver transplant patients with an initial regimen of tacrolimus (Tac), mycophenolate mofetil (MMF), and steroids. Forty-four patients were randomly allocated to the TMG+ group, and 49 patients were randomly allocated to the TMG- group. In both groups, Tac was given orally at the initial daily dose of 0.075 mg/kg twice daily, and MMF was given at the initial daily dose of 2 g/day. Steroid withdrawal was planned at 3 months after liver transplantation. The results were evaluated with respect to acute rejection incidence, patient and graft survival, graft function, and medical complications until 5 years or death for all patients. No significant differences were found between groups for the incidence of acute rejection at 5 years (11.4% versus 14.3%), 5-year patient survival (77.3% versus 87.8%), graft function, or postoperative renal function. One patient in the TMG- group underwent retransplantation. There was no difference between groups with respect to the incidence of medical complications, excepted for a higher rate of leukopenia in the TMG+ group, during the 5-year follow-up. In conclusion, the results of this prospective randomized study suggest that the addition of TMG to a triple immunosuppressive regimen (Tac, MMF, and steroids) did not modify the incidence of acute rejection episodes or long-term survival and was responsible for increased leukopenia rates.

  16. Sulfonated macro-RAFT agents for the surfactant-free synthesis of cerium oxide-based hybrid latexes.

    Science.gov (United States)

    Garnier, Jérôme; Warnant, Jérôme; Lacroix-Desmazes, Patrick; Dufils, Pierre-Emmanuel; Vinas, Jérôme; van Herk, Alex

    2013-10-01

    Three types of amphiphatic macro-RAFT agents were employed as compatibilizers to promote the polymerization reaction at the surface of nanoceria for the synthesis of CeO2-based hybrid latexes. Macro-RAFT copolymers and terpolymers were first synthesized employing various combinations of butyl acrylate as a hydrophobic monomer and acrylic acid (AA) and/or 2-acrylamido-2-methylpropane sulfonic acid (AMPS) as hydrophilic monomers. After characterizing the adsorption of these macro-RAFT agents at the cerium oxide surface by UV-visible spectrometry, emulsion copolymerization reactions of styrene and methyl acrylate were then carried out in the presence of the surface-modified nanoceria. Dynamic Light Scattering and cryo-Transmission Electron Microscopy were employed to confirm the hybrid structure of the final CeO2/polymer latexes, and proved that the presence of acrylic acid units in amphiphatic macro-RAFT agents enabled an efficient formation of hybrid structures, while the presence of AMPS units, when combined with AA units, resulted in a better distribution of cerium oxide nanoclusters between latex particles. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. Phenolic Biotransformations during Conversion of Ferulic Acid to Vanillin by Lactic Acid Bacteria

    Directory of Open Access Journals (Sweden)

    Baljinder Kaur

    2013-01-01

    Full Text Available Vanillin is widely used as food additive and as a masking agent in various pharmaceutical formulations. Ferulic acid is an important precursor of vanillin that is available in abundance in cell walls of cereals like wheat, corn, and rice. Phenolic biotransformations can occur during growth of lactic acid bacteria (LAB, and their production can be made feasible using specialized LAB strains that have been reported to produce ferulic acid esterases. The present study aimed at screening a panel of LAB isolates for their ability to release phenolics from agrowaste materials like rice bran and their biotransformation to industrially important compounds such as ferulic acid, 4-ethyl phenol, vanillic acid, vanillin, and vanillyl alcohol. Bacterial isolates were evaluated using ferulic acid esterase, ferulic acid decarboxylase, and vanillin dehydrogenase assays. This work highlights the importance of lactic acid bacteria in phenolic biotransformations for the development of food grade flavours and additives.

  18. Phylogeny of xerophilic aspergilli (subgenus Aspergillus and taxonomic revision of section Restricti

    Directory of Open Access Journals (Sweden)

    F. Sklenář

    2017-09-01

    The vast majority of species in sect. Restricti produce asperglaucide, asperphenamate or both in contrast to species in sect. Aspergillus. Mycophenolic acid was detected for the first time in at least six members of the section. The ascomata of A. halophilicus do not contain auroglaucin, epiheveadride or flavoglaucin which are common in sect. Aspergillus, but shares the echinulins with sect. Aspergillus.

  19. The influence of reducing agents on the composition of technetium-99 complexes: implications for technetium-99m radiopharmaceutical preparation

    International Nuclear Information System (INIS)

    Baldas, J.; Bonnyman, J.; Pojer, P.M.; Williams, G.A.

    1981-05-01

    The use of hydrazine or formamidine sulphinic acid as reducing agents in the presence of 99 Tc-pertechnetate anion and the diethyldithiocarbamate ligand has been found to yield complexes containing Tc triple bond N and Tc=CO bonds respectively. The nitrido nitrogen atom and the carbon monoxide incorporated in these complexes as ligands originate from the reducing agents themselves. It is apparent that when reducing agents such as hydrazine or formamidine sulphinic acid are used in the preparation of Tc-99m-radiopharmaceuticals, the possibility of the formation of complexes structurally different to those obtained by use of stannous chloride must be considered

  20. Evaluation of the efficacy of chelating agent of catechol amino carboxylic acid for removal of radiothorium

    International Nuclear Information System (INIS)

    Chen Honghong; Hu Yuxing; Wang Yinghua; Jin Meiying; Luo Meichu; Sun Meizhen

    2003-01-01

    The efficacy of prompt single and consecutive administration of chelating agent 7601 and 9501 of catechol amino carboxylic acid for the decorporation of 234 Th in rats and mice was investigated. DTPA was used as positive control. The complexing competitive abilities of 7601 and 9501 to mobilize the thorium with bovine serum albumin were studied with gel chromatography in vitro. The inhibition effect of 7601 and 9501 on superoxide anions radicals (O 2 -. ) were measured with electron spin resonance. The results showed that 7601 and 9501 could increase the excretion of 234 Th in urine and faces by 63%-70% and decrease markedly retention of 234 Th in liver and skeleton, which have been proved to be superior to DTPA. Their different bioactivities for decorporation of 234 Th were consistent with their competitive abilities to mobilize the thorium with bovine serum albumin. 7601 and 9501 could directly scavenge O 2 -. . Their effects as an O 2 -. scavenger were very significant and were similar to the of BESOD. The mechanism of protective effects of 7601 and 9501 for internal exposure injury was close related to decorporation effectiveness and the activity of scavenging oxygen free radical

  1. FTY720 versus mycophenolate mofetil in de novo renal transplantation: six-month results of a double-blind study.

    Science.gov (United States)

    Tedesco-Silva, Helio; Szakaly, Peter; Shoker, Ahmed; Sommerer, Claudia; Yoshimura, Norio; Schena, Francesco Paolo; Cremer, Malika; Hmissi, Abdel; Mayer, Hartmut; Lang, Philippe

    2007-10-15

    FTY720 is a novel immunomodulator that was developed to produce optimal graft protection with improved safety and tolerability. Phase II studies have demonstrated the efficacy of FTY720 up to the doses of 2.5 mg with full-dose cyclosporine (FDC). This multicenter, double-blind, Phase IIb, randomized study evaluated the safety and efficacy of 5 mg FTY720 (n=87; Group 1) vs. 2.5 mg FTY720 (n=90; Group 2) vs. mycophenolate mofetil (MMF; n=94; Group 3) in de novo renal transplant patients receiving FDC and prednisone. The primary efficacy endpoint was the occurrence of treated biopsy-proven acute rejection, graft loss, death, or premature study discontinuation (composite endpoint) within 6 months. The primary endpoint was superior in Group 1 (24%) and statistically noninferior in Group 2 compared to Group 3 (24.1% vs. 29.2% vs. 39.4%; P=0.025 and 0.0039, respectively). FTY720 plus FDC was generally well tolerated, with a similar incidence of adverse events across all groups. FTY720 was associated with higher incidence of bradycardia (Group 1: 26.4%, P=0.0002 and Group 2: 15.6%, P=0.046, vs. Group 3: 6.4%), respiratory disorders (Group 1: 40.2%, not significant [P=NS] and Group 2: 34.4%, P=NS vs. Group 3: 28.7%). One macular edema occurred in Group 2. Lower creatinine clearances were observed with FTY720 versus MMF (Group 1: 52.4 ml/min, P=NS and Group 2: 51.7 ml/min, P=0.039 vs. Group 3: 62.5 ml/min). Although FTY720 with FDC provided adequate protection from acute rejection the safety profile was less favorable for adverse events than current standard immunosuppression in de novo renal transplant patients.

  2. Use of citric acid for large parts decontamination

    International Nuclear Information System (INIS)

    Holland, M.E.

    1979-01-01

    Laboratory and field studies have been performed to identify and evaluate chemical decontamination agents to replace ammonium carbonate, an environmentally unacceptable compound, in the decontamination facility for large process equipment at the Portsmouth Gaseous Diffusion Plant. Preliminary screening of over 40 possible decontamination agents on the basis of efficiency, availability, toxicity, cost, corrosiveness, and practicality indicated sodium carbonate and citric acid to be the most promising. Extensive laboratory studies were performed with these two reagents. Corrosion rates, decontamination factors, uranium recovery efficiencies, technetium ( 99 Tc)/ion exchange removal effects, and possible environmental impacts were determined or investigated. Favorable results were found in all areas. Detailed monitoring and analysis during two-week trial periods in which sodium carbonate and citric acid were used in the large parts decontamination facility resulted in similar evaluation and conclusions. Because it has cleaning properties not possessed by sodium carbonate, and because it eliminated several operational problems by incorporating two acidic decontamination reagents (citric and nitric acids) instead of one basic reagent (sodium or ammonium carbonate) and one acidic reagent (nitric acid), citric acid was selected for one-year field testing. On the basis of its excellent performance in the field tests, citric acid is recommended as a permanent replacement for ammonium carbonate in the decontamination facility for large process equipment

  3. Effect of poly-α, γ, L-glutamic acid as a capping agent on morphology and oxidative stress-dependent toxicity of silver nanoparticles

    Directory of Open Access Journals (Sweden)

    Stevanović M

    2011-11-01

    Full Text Available Magdalena Stevanović1, Branimir Kovačević2, Jana Petković3, Metka Filipič3, Dragan Uskoković11Institute of Technical Sciences of Serbian Academy of Sciences and Arts, 2Institute of General and Physical Chemistry, Belgrade, Serbia; 3Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Ljubljana, SloveniaAbstract: Highly stable dispersions of nanosized silver particles were synthesized using a straightforward, cost-effective, and ecofriendly method. Nontoxic glucose was utilized as a reducing agent and poly- α, γ, L-glutamic acid (PGA, a naturally occurring anionic polymer, was used as a capping agent to protect the silver nanoparticles from agglomeration and render them biocompatible. Use of ammonia during synthesis was avoided. Our study clearly demonstrates how the concentration of the capping agent plays a major role in determining the dimensions, morphology, and stability, as well as toxicity of a silver colloidal solution. Hence, proper optimization is necessary to develop silver colloids of narrow size distribution. The samples were characterized by Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, field-emission scanning electron microscopy, transmission electron microscopy, and zeta potential measurement. MTT assay results indicated good biocompatibility of the PGA-capped silver nanoparticles. Formation of intracellular reactive oxygen species was measured spectrophotometrically using 2,7-dichlorofluorescein diacetate as a fluorescent probe, and it was shown that the PGA-capped silver nanoparticles did not induce intracellular formation of reactive oxygen species.Keywords: silver nanoparticles, poly-α, γ, L-glutamic, green synthesis, morphology, cytotoxicity

  4. Prevention of diabetes: effect of mycophenolate mofetil and anti-CD25 on onset of diabetes in the DRBB rat.

    Science.gov (United States)

    Ugrasbul, Figen; Moore, Wayne V; Tong, Pei Ying; Kover, Karen L

    2008-12-01

    Anti-CD25 and mycophenolate mofetil (MMF) treatment of patients with new-onset diabetes is currently being tested as one of the trials in TrialNet. We tested the effectiveness of MMF and anti-CD25 in preventing autoimmune diabetes in the diabetes-resistant biobreeding (DRBB) rat. Autoimmune diabetes in the DRBB rat was induced with a Treg cell depletion regimen starting at 24-26 d of age. Treatment was started on the first day of the depletion regimen in the following groups: (i) control (vehicle); (ii) MMF 25 mg/kg/d intramuscularly daily for 8 wk; (iii) anti-CD25 0.8 mg/kg/d intraperitoneally 5 d/wk for 3 wk; and (iv) combination of MMF and anti-CD25. In a second set of experiments, treatments were started on day 5 of the depletion regimen (delayed treatment) with groups 1, 3, and 4. Rats that had diabetes-free survival for at least 30 d after the treatment was stopped underwent a second Treg depletion (redepletion). In each of the three treatment groups (n = 10/group), onset of diabetes was delayed or prevented in 20, 40 and 80% in groups 2, 3, and 4, respectively. After redepletion, diabetes-free survival was unchanged in group 2 and decreased to 10 and 30% in groups 3 and 4, respectively. With delayed treatment, groups 3 and 4 had 33 and 50% diabetes-free survival that decreased to 0 and 33% after redepletion. MMF and anti-CD25 alone or in combination are effective in delaying and preventing diabetes in the DRBB rat especially if treatment is started before stimulation and expansion of the autoreactive T cells.

  5. Surface fixation of dried blood by glutaraldehyde and peracetic acid.

    Science.gov (United States)

    Kampf, G; Bloss, R; Martiny, H

    2004-06-01

    The difficulties of successful prion inactivation by chemical agents has led to changes in recommendations regarding the reprocessing of instruments including flexible endoscopes. One of the changes is the preference for peracetic acid instead of glutaraldehyde in order to avoid fixation of organic material, but the surface fixation by various active agents has not been fully investigated. We used a standardized amount of dried blood soil on metal carriers (on average 22 mg). One part of the carriers was exposed to different disinfectants (four based on peracetic acid, three based on glutaraldehyde, two based on quaternary ammonium compounds (QAC), one based on QAC and amines, one based on phenols and one cleaning agent) and air dried. The difference compared with the non-exposed soiled carrier was taken as the measure of blood removal by exposure to the disinfectants. In addition the other part of the carriers was exposed to a cleaning agent and air dried. The cleaning agent itself was capable of removing more than 99% of the dried blood and served as a control for non-fixation. The rate of fixation of dried blood was calculated as the ratio of the weight of residual soil on 'soiled, disinfected and cleaned' carriers and on 'soiled and disinfected' carriers. All experiments were repeated eight times. Blood removal varied between 90.3% +/- 1.5% (phenol-based disinfectant) and peracetic acid. No other preparations showed a potential for blood fixation (peracetic acid, and support the evidence that effective cleaning should precede the chemical disinfection. Copyright 2004 The Hospital Infection Society

  6. Combination of aspartic acid and glutamic acid inhibits tumor cell proliferation.

    Science.gov (United States)

    Yamaguchi, Yoshie; Yamamoto, Katsunori; Sato, Yoshinori; Inoue, Shinjiro; Morinaga, Tetsuo; Hirano, Eiichi

    2016-01-01

    Placental extract contains several biologically active compounds, and pharmacological induction of placental extract has therapeutic effects, such as improving liver function in patients with hepatitis or cirrhosis. Here, we searched for novel molecules with an anti-tumor activity in placental extracts. Active molecules were separated by chromatographic analysis, and their antiproliferative activities were determined by a colorimetric assay. We identified aspartic acid and glutamic acid to possess the antiproliferative activity against human hepatoma cells. Furthermore, we showed that the combination of aspartic acid and glutamic acid exhibited enhanced antiproliferative activity, and inhibited Akt phosphorylation. We also examined in vivo tumor inhibition activity using the rabbit VX2 liver tumor model. The treatment mixture (emulsion of the amino acids with Lipiodol) administered by hepatic artery injection inhibited tumor cell growth of the rabbit VX2 liver. These results suggest that the combination of aspartic acid and glutamic acid may be useful for induction of tumor cell death, and has the potential for clinical use as a cancer therapeutic agent.

  7. Aluminum bioavailability from the approved food additive leavening agent acidic sodium aluminum phosphate, incorporated into a baked good, is lower than from water.

    Science.gov (United States)

    Yokel, Robert A; Florence, Rebecca L

    2006-10-03

    There are estimates of oral aluminum (Al) bioavailability from drinking water, but little information on Al bioavailability from foods. Foods contribute approximately 95% and drinking water 1-2% of the typical human's daily Al intake. The objectives were to estimate oral Al bioavailability from a representative food containing the food additive acidic sodium aluminum phosphate (acidic SALP), a leavening agent in baked goods. Rats were acclimated to a special diet that resulted in no stomach contents 14 h after its withdrawal. They were trained to rapidly consume a biscuit containing 1.5% acidic SALP. Oral Al bioavailability was then determined from a biscuit containing 1% or 2% acidic SALP, synthesized to contain (26)Al. The rats received concurrent (27)Al infusion. Blood was repeatedly withdrawn and serum analyzed for (26)Al by accelerator mass spectrometry. Total Al was determined by atomic absorption spectrometry. Oral (26)Al bioavailability was determined from the area under the (26)Al, compared to (27)Al, serum concentrationxtime curves. Oral Al bioavailability (F) from biscuit containing 1% or 2% acidic (26)Al-SALP averaged approximately 0.11% and 0.13%; significantly less than from water, which was previously shown to be approximately 0.3%. The time to maximum serum (26)Al concentration was 4.2 and 6h after consumption of biscuit containing 1% or 2% (26)Al-acidic SALP, respectively, compared to 1-2h following (26)Al in water. These results of oral Al bioavailability from acidic (26)Al-SALP in a biscuit (F approximately 0.1%) and results from (26)Al in water (F approximately 0.3%) x the contributions of food and drinking water to the typical human's daily Al intake ( approximately 5-10mg from food and 0.1mg from water, respectively) suggest food provides approximately 25-fold more Al to systemic circulation, and potential Al body burden, than does drinking water.

  8. Aluminum bioavailability from the approved food additive leavening agent acidic sodium aluminum phosphate, incorporated into a baked good, is lower than from water

    International Nuclear Information System (INIS)

    Yokel, Robert A.; Florence, Rebecca L.

    2006-01-01

    There are estimates of oral aluminum (Al) bioavailability from drinking water, but little information on Al bioavailability from foods. Foods contribute ∼95% and drinking water 1-2% of the typical human's daily Al intake. The objectives were to estimate oral Al bioavailability from a representative food containing the food additive acidic sodium aluminum phosphate (acidic SALP), a leavening agent in baked goods. Rats were acclimated to a special diet that resulted in no stomach contents 14 h after its withdrawal. They were trained to rapidly consume a biscuit containing 1.5% acidic SALP. Oral Al bioavailability was then determined from a biscuit containing 1% or 2% acidic SALP, synthesized to contain 26 Al. The rats received concurrent 27 Al infusion. Blood was repeatedly withdrawn and serum analyzed for 26 Al by accelerator mass spectrometry. Total Al was determined by atomic absorption spectrometry. Oral 26 Al bioavailability was determined from the area under the 26 Al, compared to 27 Al, serum concentration x time curves. Oral Al bioavailability (F) from biscuit containing 1% or 2% acidic 26 Al-SALP averaged ∼0.11% and 0.13%; significantly less than from water, which was previously shown to be ∼0.3%. The time to maximum serum 26 Al concentration was 4.2 and 6 h after consumption of biscuit containing 1% or 2% 26 Al-acidic SALP, respectively, compared to 1-2 h following 26 Al in water. These results of oral Al bioavailability from acidic 26 Al-SALP in a biscuit (F ∼ 0.1%) and results from 26 Al in water (F ∼ 0.3%) x the contributions of food and drinking water to the typical human's daily Al intake (∼5-10 mg from food and 0.1 mg from water, respectively) suggest food provides ∼25-fold more Al to systemic circulation, and potential Al body burden, than does drinking water

  9. Chemical modification of cobalt ferrite nanoparticles with possible application as asphaltene flocculant agent

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, G.E.; Clarindo, J.E.S.; Santo, K.S.E., E-mail: geiza.oliveira@ufes.br [Universidade Federal do Espirito Santo (CCE/DQUI/UFES), Vitoria, ES (Brazil). Centro de Ciencias Exatas. Dept. de Quimica; Souza Junior, F.G. [Universidade Federal do Rio de Janeiro (IMA/UFRJ), Rio de Janeiro, RJ (Brazil). Instituto de Macromoleculas

    2013-11-01

    Asphaltenes can cause enormous losses in the oil industry, because they are soluble only in aromatic solvents. Therefore, they must be removed from the petroleum before it is refined, using flocculant agents. Aiming to find new materials that can work as flocculant agents to asphaltenes, cobalt ferrite nanoparticles were chemically modified through acid-base reactions using dodecylbenzene sulfonic acid (DBSA) to increase their lipophilicity. Nanoparticle synthesis was performed using the co-precipitation method followed by annealing of these nanoparticles, aiming to change the structural phase. Modified and unmodified nanoparticles were tested by FTIR-ATR, XRD and TGA/DTA. In addition, precipitation onset of the asphaltenes was performed using modified and unmodified nanoparticles. These tests showed that modified nanoparticles have a potential application as flocculant agents used to remove asphaltenes before oil refining, since the presence of nanoparticles promotes the asphaltene precipitation onset with the addition of a small amount of non-solvent (author)

  10. Chemical modification of cobalt ferrite nanoparticles with possible application as asphaltene flocculant agent

    International Nuclear Information System (INIS)

    Oliveira, G.E.; Clarindo, J.E.S.; Santo, K.S.E.; Souza Junior, F.G.

    2013-01-01

    Asphaltenes can cause enormous losses in the oil industry, because they are soluble only in aromatic solvents. Therefore, they must be removed from the petroleum before it is refined, using flocculant agents. Aiming to find new materials that can work as flocculant agents to asphaltenes, cobalt ferrite nanoparticles were chemically modified through acid-base reactions using dodecylbenzene sulfonic acid (DBSA) to increase their lipophilicity. Nanoparticle synthesis was performed using the co-precipitation method followed by annealing of these nanoparticles, aiming to change the structural phase. Modified and unmodified nanoparticles were tested by FTIR-ATR, XRD and TGA/DTA. In addition, precipitation onset of the asphaltenes was performed using modified and unmodified nanoparticles. These tests showed that modified nanoparticles have a potential application as flocculant agents used to remove asphaltenes before oil refining, since the presence of nanoparticles promotes the asphaltene precipitation onset with the addition of a small amount of non-solvent (author)

  11. Glutamic acid and its derivatives: candidates for rational design of anticancer drugs.

    Science.gov (United States)

    Ali, Imran; Wani, Waseem A; Haque, Ashanul; Saleem, Kishwar

    2013-05-01

    Throughout the history of human civilizations, cancer has been a major health problem. Its treatment has been interesting but challenging to scientists. Glutamic acid and its derivative glutamine are known to play interesting roles in cancer genesis, hence, it was realized that structurally variant glutamic acid derivatives may be designed and developed and, might be having antagonistic effects on cancer. The present article describes the state-of-art of glutamic acid and its derivatives as anticancer agents. Attempts have been made to explore the effectivity of drug-delivery systems based on glutamic acid for the delivery of anticancer drugs. Moreover, efforts have also been made to discuss the mechanism of action of glutamic acid derivatives as anticancer agents, clinical applications of glutamic acid derivatives, as well as recent developments and future perspectives of glutamic acid drug development have also been discussed.

  12. Advanced Contrast Agents for Multimodal Biomedical Imaging Based on Nanotechnology.

    Science.gov (United States)

    Calle, Daniel; Ballesteros, Paloma; Cerdán, Sebastián

    2018-01-01

    Clinical imaging modalities have reached a prominent role in medical diagnosis and patient management in the last decades. Different image methodologies as Positron Emission Tomography, Single Photon Emission Tomography, X-Rays, or Magnetic Resonance Imaging are in continuous evolution to satisfy the increasing demands of current medical diagnosis. Progress in these methodologies has been favored by the parallel development of increasingly more powerful contrast agents. These are molecules that enhance the intrinsic contrast of the images in the tissues where they accumulate, revealing noninvasively the presence of characteristic molecular targets or differential physiopathological microenvironments. The contrast agent field is currently moving to improve the performance of these molecules by incorporating the advantages that modern nanotechnology offers. These include, mainly, the possibilities to combine imaging and therapeutic capabilities over the same theranostic platform or improve the targeting efficiency in vivo by molecular engineering of the nanostructures. In this review, we provide an introduction to multimodal imaging methods in biomedicine, the sub-nanometric imaging agents previously used and the development of advanced multimodal and theranostic imaging agents based in nanotechnology. We conclude providing some illustrative examples from our own laboratories, including recent progress in theranostic formulations of magnetoliposomes containing ω-3 poly-unsaturated fatty acids to treat inflammatory diseases, or the use of stealth liposomes engineered with a pH-sensitive nanovalve to release their cargo specifically in the acidic extracellular pH microenvironment of tumors.

  13. Clinical study of CT-guided sclerotherapy using 50 percent acetic acid in the treatment of renal cyst

    International Nuclear Information System (INIS)

    Pang Jun; Han Changli; Zhang Zhaofu; Dai Jingru

    2007-01-01

    Objective: To investigate the efficacy of 50% acetic acid as a renal cyst sclerotherapy agent, and with further comparison to that of absolute alcohol. Methods: Eighty five patients with renal cyst were undergone sclerotherapy through spiral CT guidance including 43 cases with absolute alcohol and the others with 50% acetic acid as selerosing agents. All the cysts were aspirated under CT-guidance, beforehand. The selerosising agents were withdrawn from the cysts after a definite period of retention. Results: The disappearance rates of cyst cavity with absolute alcohol and acetic acid were 55.81% and 71.42%, respectively. Complication occurenee rates with absolute alcohol and acetic acid were 16.28% and 4.76%, respectively. The average retention periods of absolute alcohol and acetic acid in cyst were (20±4) minutes, and (10±2)minutes, respectively. Statistical analysis demonstrated that all the data in two groups were significantly different. Conclusion: Using 50% acetic acid as sclerosising agent in treating renal cyst possesses the better effect and less side effect, providing a tendency to replace the traditional therapy. (authors)

  14. Simultaneous Removal of Lindane, Lead and Cadmium from Soils by Rhamnolipids Combined with Citric Acid

    Science.gov (United States)

    Long, Tao; Ying, Rongrong; Ye, Mao; Zhang, Shengtian; Li, Qun; Zhou, Yan; Lin, Yusuo

    2015-01-01

    This study investigated the performance of rhamnolipids-citric acid mixed agents in simultaneous desorption of lindane and heavy metals from soils. The capacity of the mixed agents to solubilize lindane, lead and cadmium in aqueous solution was also explored. The results showed that the presence of citric acid greatly enhanced the solubilization of lindane and cadmium by rhamnolipids. A combined effect of the mixed agents on lindane and heavy metals removal from soils was observed. The maximum desorption ratios for lindane, cadmium and lead were 85.4%, 76.4% and 28.1%, respectively, for the mixed agents containing 1% rhamnolipidsand 0.1 mol/L citric acid. The results also suggest that the removal efficiencies of lead and cadmium were strongly related to their speciations in soils, and metals in the exchangeable and carbonate forms were easier to be removed. Our study suggests that the combining use of rhamnolipids and citric acid is a promising alternative to simultaneously remove organochlorine pesticides and heavy metals from soils. PMID:26087302

  15. Carboxylic acid exchangers in analytical chemistry

    International Nuclear Information System (INIS)

    Venkateswarlu, Ch.

    1976-01-01

    The literature on the use of carboxylic acid exchangers in inorganic analytical chemistry is reviewed. It is classified under two heads, based on the ionic form in which the exchanger is employed, viz., the salt form and the acid form. In the salt form, the separations reported in the beginning are mostly carried out in alkaline medium, employing ammonia and its derivatives as complexing agents to hold cations in solution. This was followed by the use of ammonium ion as an eluent from heavy weakly or neutral solutions. There are a few separations reported making use of EDTA as eluent. It appears that separation of some anions from cations can be achieved with greater ease with these exchangers than with sulphonic acid type. Contary to the general belief, carboxylic acid exchangers are used in H + form to achieve some analytical separations of cations of interest. These exchangers exhibit better sorption of some cations in presence of complexing agents containing basic nitrogen as a donor. In fact, a careful study of these exchangers with different matrices might yield really selective exchangers, than the chelating ones known commercially. From the separation cited, carboxylic acid exchangers appear to have greater potentialities in their applications, than what is normally expected. (author)

  16. Analysis of chemical warfare agents in food products by atmospheric pressure ionization-high field asymmetric waveform ion mobility spectrometry-mass spectrometry.

    Science.gov (United States)

    Kolakowski, Beata M; D'Agostino, Paul A; Chenier, Claude; Mester, Zoltán

    2007-11-01

    Flow injection high field asymmetric waveform ion mobility spectrometry (FAIMS)-mass spectrometry (MS) methodology was developed for the detection and identification of chemical warfare (CW) agents in spiked food products. The CW agents, soman (GD), sarin (GB), tabun (GA), cyclohexyl sarin (GF), and four hydrolysis products, ethylphosphonic acid (EPA), methylphosphonic acid (MPA), pinacolyl methylphosphonic acid (Pin MPA), and isopropyl methylphosphonic acid (IMPA) were separated and detected by positive ion and negative ion atmospheric pressure ionization-FAIMS-MS. Under optimized conditions, the compensation voltages were 7.2 V for GD, 8.0 V for GA, 7.2 V for GF, 7.6 V for GB, 18.2 V for EPA, 25.9 V for MPA, -1.9 V for PinMPA, and +6.8 V for IMPA. Sample preparation was kept to a minimum, resulting in analysis times of 3 min or less per sample. The developed methodology was evaluated by spiking bottled water, canola oil, cornmeal, and honey samples at low microgram per gram (or microg/mL) levels with the CW agents or CW agent hydrolysis products. The detection limits observed for the CW agents in the spiked food samples ranged from 3 to 15 ng/mL in bottled water, 1-33 ng/mL in canola oil, 1-34 ng/g in cornmeal, and 13-18 ng/g in honey. Detection limits were much higher for the CW agent hydrolysis products, with only MPA being detected in spiked honey samples.

  17. Effect of capping agents on optical and antibacterial properties

    Indian Academy of Sciences (India)

    Cadmium selenide quantum dots (CdSe QDs) were synthesized in aqueous phase by the freezing temperature injection technique using different capping agents (viz. thioglycolic acid, 1-thioglycerol, L-cysteine). Absorption spectra of CdSe QDs exhibited a blue shift as compared to its bulk counterpart, which is an indication ...

  18. Green reduction of graphene oxide by ascorbic acid

    Science.gov (United States)

    Khosroshahi, Zahra; Kharaziha, Mahshid; Karimzadeh, Fathallah; Allafchian, Alireza

    2018-01-01

    Graphene, a single layer of sp2-hybridized carbon atoms in a hexagonal (two-dimensional honey-comb) lattice, has attracted strong scientific and technological interest due to its novel and excellent optical, chemical, electrical, mechanical and thermal properties. The solution-processable chemical reduction of Graphene oxide (GO is considered as the most favorable method regarding mass production of graphene. Generally, the reduction of GO is carried out by chemical approaches using different reductants such as hydrazine and sodium borohydride. These components are corrosive, combustible and highly toxic which may be dangerous for personnel health and the environment. Hence, these reducing agents are not promising choice for reducing of graphene oxide (GO). As a consequence, it is necessary for further development and optimization of eco-friendly, natural reducing agent for clean and effective reduction of GO. Ascorbic acid, an eco-friendly and natural reducing agents, having a mild reductive ability and nontoxic property. So, the aim of this research was to green synthesis of GO with ascorbic acid. For this purpose, the required amount of NaOH and ascorbic acid were added to GO solution (0.5 mg/ml) and were heated at 95 °C for 1 hour. According to the X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and electrochemical results, GO were reduced with ascorbic acid like hydrazine with better electrochemical properties and ascorbic acid is an ideal substitute for hydrazine in the reduction of graphene oxide process.

  19. CHARACTERIZATION OF SORBENT PRODUCED THROUGH IMMOBILIZATION OF HUMIC ACID ON CHITOSAN USING GLUTARALDEHYDE AS CROSS-LINKING AGENT AND Pb(II ION AS ACTIVE SITE PROTECTOR

    Directory of Open Access Journals (Sweden)

    Uripto Trisno Santoso

    2010-12-01

    Full Text Available Sorbent produced through immobilization of humic acid (HA on chitosan using glutaraldehyde as cross-linking agent and Pb(II ions as active site protector has been characterized. Active sorption site of HA was protected by reacting HA with Pb(II ion, and the protected-HA was then activated by glutaraldehyde, crosslinked onto chitosan, and deprotected by 0.1 M disodium ethylenediamine tetra-acetic acid (Na2EDTA. The protected-crosslinking method enhanced the content of immobilized-HA and its chemical stability. Based on the FTIR spectra, crosslinking of HA on chitosan probably occurred through a chemical reaction. The sorption capacity of sorbent still remains unchanged after the second regeneration, but some of HA start to be soluble. The latter shows that cross-linking reaction between HA and chitosan is through formation an unstable product. The effectiveness of sorbent regeneration can also be identified by the XRD pattern.

  20. Crystal growth vs. conventional acid etching: A comparative evaluation of etch patterns, penetration depths, and bond strengths

    Directory of Open Access Journals (Sweden)

    Devanna Raghu

    2008-01-01

    Full Text Available The present study was undertaken to investigate the effect on enamel surface, penetration depth, and bond strength produced by 37% phosphoric acid and 20% sulfated polyacrylic acid as etching agents for direct bonding. Eighty teeth were used to study the efficacy of the etching agents on the enamel surface, penetration depth, and tensile bond strength. It was determined from the present study that a 30 sec application of 20% sulfated polyacrylic acid produced comparable etching topography with that of 37% phosphoric acid applied for 30 sec. The 37% phosphoric acid dissolves enamel to a greater extent than does the 20% sulfated polyacrylic acid. Instron Universal testing machine was used to evaluate the bond strengths of the two etching agents. Twenty percent sulfated polyacrylic acid provided adequate tensile bond strength. It was ascertained that crystal growth can be an alternative to conventional phosphoric acid etching as it dissolves lesser enamel and provides adequate tensile bond strength.

  1. Oxygen uptake during the γ-irradiation of fatty acids

    International Nuclear Information System (INIS)

    Metwally, M.M.K.; Moore, J.S.

    1987-01-01

    The radiation-induced oxidation of saturated and unsaturated fatty acids in aqueous solutions has been estimated by measurement of the continuous uptake of oxygen using an oxygen electrode. Chain reactions, initiated by HO radicals, are easily identified to be occurring in the case of unsaturated fatty acids. Other mild oxidation agents, namely (SCN)2 -anion radicals, Br 2 - anion radicals and N 3 -anion radicals, are also found to be capable of oxidizing the polyunsaturated fatty acids. Evidence is presented the O 2- anion radicals may also initiate peroxidation. The oxidation of the polyunsaturated fatty acids is dependent on dose rate, fatty acid concentration, temperature and the presence of antioxidant and other protective agents. Kinetic studies of the reaction of (SCN)2 - anion radicals and Br 2 - anion radicals with linoleic and linolenic acids have been carried out using pulse radiolysis. The bimolecular rate constants for both radical species with the lipids are approx 10 7 mol-? 1 dm 3 s -1 , below their critical micelle concentrations, and decrease at higher concentrations due to micelle formation. (author)

  2. 21 CFR 173.280 - Solvent extraction process for citric acid.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Solvent extraction process for citric acid. 173.280... HUMAN CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.280 Solvent extraction process for citric acid. A solvent extraction process for recovery of citric acid from...

  3. Metal extraction by amides of carboxylic acids

    International Nuclear Information System (INIS)

    Skorovarov, D.I.; Chumakova, G.M.; Rusin, L.I.; Ul'anov, V.S.; Sviridova, R.A.; Sviridov, A.L.

    1988-01-01

    Extraction ability of various amides was studied. Data on extraction of rare earths, vanadium, molybdenum, rhenium, uranium, niobium, tantalum by N,N-dibutyl-amides of acetic, nonanic acids and fatly synthetic acids of C 7 -C 9 fractions are presented. Effect of salting-out agents, inorganic acid concentrations on extraction process was studied. Potential ability of using amides of carboxylic acids for extractional concentration of rare earths as well as for recovery and separation of iron, rhenium, vanadium, molybdenum, uranium, niobium, and tantalum was shown

  4. Bile acids: regulation of apoptosis by ursodeoxycholic acid.

    Science.gov (United States)

    Amaral, Joana D; Viana, Ricardo J S; Ramalho, Rita M; Steer, Clifford J; Rodrigues, Cecília M P

    2009-09-01

    Bile acids are a group of molecular species of acidic steroids with peculiar physical-chemical and biological characteristics. At high concentrations they become toxic to mammalian cells, and their presence is pertinent in the pathogenesis of several liver diseases and colon cancer. Bile acid cytoxicity has been related to membrane damage, but also to nondetergent effects, such as oxidative stress and apoptosis. Strikingly, hydrophilic ursodeoxycholic acid (UDCA), and its taurine-conjugated form (TUDCA), show profound cytoprotective properties. Indeed, these molecules have been described as potent inhibitors of classic pathways of apoptosis, although their precise mode of action remains to be clarified. UDCA, originally used for cholesterol gallstone dissolution, is currently considered the first choice therapy for several forms of cholestatic syndromes. However, the beneficial effects of both UDCA and TUDCA have been tested in other experimental pathological conditions with deregulated levels of apoptosis, including neurological disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Here, we review the role of bile acids in modulating the apoptosis process, emphasizing the anti-apoptotic effects of UDCA and TUDCA, as well as their potential use as novel and alternate therapeutic agents for the treatment of apoptosis-related diseases.

  5. Preparation of carbon black masterbatch for PET using polymeric dispersing agents

    Energy Technology Data Exchange (ETDEWEB)

    Oh, D.H. [Kyungpook National University, Taegu (Korea, Republic of); Lim, J.C. [Pukyong National University, Pusan (Korea, Republic of); Seo, K.H. [Yeungnam College of Science and Technology, Taegu (Korea, Republic of)

    1999-03-01

    Three kinds of copolyesters, dispersing agents, were synthesized from the polycondensation reaction of dimethylterephthalate (DMT), dimethylisophthalate (DMI), sebacic acid (SA), and 1,4-butanediol (BD). Carbon black masterbatches were prepared by mixing carbon black into the dispersing agents (1 : 1.3 weight ratio) in a Brabender Plasticorder Using single screw extruder, masterbatches were compounded with poly(ethylene terephthalate) in 3 wt% concentration and mechanical properties of the compounds were investigated Gel permeation chromatography data implied that thermal degradation of polymeric dispersing agents was not significant through dispersion. Capillary rheometer test showed that PBTI has the highest viscosity and shear sensitivity among the there dispersing agents. Volume resistivities of masterbatch and transmission electron micrographs showed that dispersity of carbon black was improved with increasing melt viscosity of dispersing agent. The ultimate performance and mechanical characteristics of carbon black filled PET compounds depended directly on dispersion quality of the carbon black in masterbatch. Mechanical properties of compounds were improved with increasing dispersity of carbon black and with increasing content of rigid aromatic group in the copolyester dispersing agent. 30 refs., 9 figs., 5 tabs.

  6. NaVirCept - Nucleic Acid-Based Anti-Viral Project

    International Nuclear Information System (INIS)

    Stephen, E. R.; Wong, J.; Van Loon, D.

    2007-01-01

    Vaccines are generally considered to be the most effective countermeasures to bacterial and viral diseases, however, licensed vaccines against many disease agents are either not available or their efficacies have not been demonstrated. Vaccines are generally agent specific in terms of treatment spectrum and are subject to defeat through natural mutation or through directed efforts. With respect to viral therapeutics, one of the major limitations associated with antiviral drugs is acquired drug resistance caused by antigenic shift or drift. A number of next-generation prophylactic and/or therapeutic measures are on the horizon. Of these, nucleic acid-based drugs are showing great antiviral potential. These drugs elicit long-lasting, broad spectrum protective immune responses, especially to respiratory viral pathogens. The Nucleic Acid-Based Antiviral (NaVirCept) project provides the opportunity to demonstrate the effectiveness of novel medical countermeasures against military-significant endemic and other viral threat agents. This project expands existing DRDC drug delivery capability development, in the form of proprietary liposome intellectual property, by coupling it with leading-edge nucleic acid-based technology to deliver effective medical countermeasures that will protect deployed personnel and the warfighter against a spectrum of viral disease agents. The technology pathway will offer a means to combat emerging viral diseases or modified threat agents such as the bird flu or reconstructed Spanish flu without going down the laborious, time-consuming and expensive paths to develop countermeasures for each new and/or emerging viral disease organism.(author)

  7. Electrophoretic deposition of composite halloysite nanotube–hydroxyapatite–hyaluronic acid films

    Energy Technology Data Exchange (ETDEWEB)

    Deen, I. [Department of Materials Science and Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L7 (Canada); Zhitomirsky, I., E-mail: zhitom@mcmaster.ca [Department of Materials Science and Engineering, McMaster University, 1280 Main Street West, Hamilton, Ontario, Canada L8S 4L7 (Canada)

    2014-02-15

    Highlights: ► Composite halloysite nanotubes–hydroxyapatite–hyaluronic acid films were prepared. ► Electrophoretic deposition method was used for deposition. ► Natural hyaluronic acid was used as a dispersing, charging and film forming agent. ► Film composition and deposition yield can be varied. ► The films can be used for biomedical implants with controlled release of drugs. -- Abstract: Electrophoretic deposition method has been developed for the deposition of biocomposite films containing halloysite nanotubes (HNTs), hydroxyapatite (HA) and hyaluronic acid. The method is based on the use of natural hyaluronate biopolymer as a dispersing and charging agent for HNT and HA and film forming agent for the fabrication of the composite films. The deposition kinetics was studied by the quartz crystal microbalance method. The composite films were studied by X-ray diffraction, thermogravimetric analysis, differential thermal analysis and electron microscopy. The composite films are promising materials for the fabrication of biomedical implants with advanced functional properties.

  8. Electrophoretic deposition of composite halloysite nanotube–hydroxyapatite–hyaluronic acid films

    International Nuclear Information System (INIS)

    Deen, I.; Zhitomirsky, I.

    2014-01-01

    Highlights: ► Composite halloysite nanotubes–hydroxyapatite–hyaluronic acid films were prepared. ► Electrophoretic deposition method was used for deposition. ► Natural hyaluronic acid was used as a dispersing, charging and film forming agent. ► Film composition and deposition yield can be varied. ► The films can be used for biomedical implants with controlled release of drugs. -- Abstract: Electrophoretic deposition method has been developed for the deposition of biocomposite films containing halloysite nanotubes (HNTs), hydroxyapatite (HA) and hyaluronic acid. The method is based on the use of natural hyaluronate biopolymer as a dispersing and charging agent for HNT and HA and film forming agent for the fabrication of the composite films. The deposition kinetics was studied by the quartz crystal microbalance method. The composite films were studied by X-ray diffraction, thermogravimetric analysis, differential thermal analysis and electron microscopy. The composite films are promising materials for the fabrication of biomedical implants with advanced functional properties

  9. Uranium recovery from wet-process phosphoric acid

    International Nuclear Information System (INIS)

    McCullough, J.F.; Phillips, J.F. Jr.; Tate, L.R.

    1979-01-01

    A method of recovering uranium from wet-process phosphoric acid is claimed where the acid is treated with a mixture of an ammonium salt or ammonia, a reducing agent, and then a miscible solvent. Solids are separated from the phosphoric acid liquid phase. The solid consists of a mixture of metal phosphates and uranium. It is washed free of adhering phosphoric acid with fresh miscible solvent. The solid is dried and dissolved in acid whereupon uranium is recovered from the solution. Miscible solvent and water are distilled away from the phosphoric acid. The distillate is rectified and water discarded. All miscible solvent is recovered for recycle. 5 claims

  10. Chelating agents related to ethylenediamine bis(2-hydroxyphenyl)acetic acid (EDDHA): synthesis, characterization, and equilibrium studies of the free ligands and their Mg2+, Ca2+, Cu2+, and Fe3+ chelates.

    Science.gov (United States)

    Yunta, Felipe; García-Marco, Sonia; Lucena, Juan J; Gómez-Gallego, Mar; Alcázar, Roberto; Sierra, Miguel A

    2003-08-25

    Iron chelates such as ethylenediamine-N,N'-bis(2-hydroxyphenyl)acetic acid (EDDHA) and their analogues are the most efficient soil fertilizers to treat iron chlorosis in plants growing in calcareous soils. EDDHA, EDDH4MA (ethylenediamine-N,N'-bis(2-hydroxy-4-methylphenyl)acetic acid), and EDDCHA (ethylenediamine-N,N'-bis(2-hydroxy-5-carboxyphenyl)acetic acid) are allowed by the European directive, but also EDDHSA (ethylenediamine-N,N'-bis(2-hydroxy-5-sulfonylphenyl)acetic acid) and EDDH5MA (ethylenediamine-N,N'-bis(2-hydroxy-5-methylphenyl)acetic acid) are present in several commercial iron chelates. In this study, these chelating agents as well as p,p-EDDHA (ethylenediamine-N,N'-bis(4-hydroxyphenyl)acetic acid) and EDDMtxA (ethylenediamine-N,N'-bis(2-metoxyphenyl)acetic acid) have been obtained following a new synthetic pathway. Their chemical behavior has been studied to predict the effect of the substituents in the benzene ring on their efficacy as iron fertilizers for soils above pH 7. The purity of the chelating agents has been determined using a novel methodology through spectrophotometric titration at 480 nm with Fe(3+) as titrant to evaluate the inorganic impurities. The protonation constants were determined by both spectrophotometric and potentiometric methods, and Ca(2+) and Mg(2+) stability constants were determined from potentiometric titrations. To establish the Fe(3+) and Cu(2+) stability constants, a new spectrophotometric method has been developed, and the results were compared with those reported in the literature for EDDHA and EDDHMA and their meso- and rac-isomers. pM values have been also determined to provide a comparable basis to establish the relative chelating ability of these ligands. The purity obtained for the ligands is higher than 87% in all cases and is comparable with that obtained by (1)H NMR. No significant differences have been found among ligands when their protonation and stability constants were compared. As expected, no Fe(3

  11. Investigations of the uptake of transuranic radionuclides by humic and fulvic acids chemically immobilized on silica gel and their competitive release by complexing agents

    International Nuclear Information System (INIS)

    Bulman, R.A.; Szabo, G.; Clayton, R.F.; Clayton, C.R.

    1998-01-01

    The chemistry of the interactions of transuranic elements (TUs) with humic substances needs to be understood so that humate-mediated movement of transuranic radionuclides through the environment can be predicted. This paper reports the chemical immobilization on silica gel of humic and fulvic acids and evaluates the potential of these new materials for the retention of Pu and Am. In addition to the preparation of the foregoing immobilized humic substances, other low molecular weight metal-binding ligands have also been immobilized on silica gel to investigate the binding sites for transuranic elements (TUs) in humic substances. The X-ray photoelectron spectra (XPS) of Th(IV) complexed by humic acid and the immobilized humic acid are similar thus it appears that immobilization of humic acid does not generate any configurational changes in the Th(IV)-binding sites of the macromolecule. A variety of chelating agents partly mobilize these TUs sorbed on the solid phases. A batch method was used to determine the distribution coefficients (R d ) of Pu and Am between the silica gels and aqueous solutions of phosphate and citrate. The effects of the immobilized ligands, the anions and pH in the solution on sorption were assessed. Distributed coefficients (R d ) for the uptake of Pu and Am by these prepared solid phases are, in some cases, of a similar order of magnitude as those determined for soil and particles suspended in terrestrial surface waters

  12. Detection of Chemical/Biological Agents and Stimulants using Quadrupole Ion Trap Mass Spectrometry

    International Nuclear Information System (INIS)

    Harmon, S.H.; Hart, K.J.; Vass, A.A.; Wise, M.B.; Wolf, D.A.

    1999-01-01

    Detection of Chemical/Biological Agents and Simulants A new detector for chemical and biological agents is being developed for the U. S. Army under the Chemical and Biological Mass Spectrometer Block II program. The CBMS Block II is designed to optimize detection of both chemical and biological agents through the use of direct sampling inlets[I], a multi- ported sampling valve and a turbo- based vacuum system to support chemical ionization. Unit mass resolution using air as the buffer gas[2] has been obtained using this design. Software to control the instrument and to analyze the data generated from the instrument has also been newly developed. Detection of chemical agents can be accomplished. using the CBMS Block II design via one of two inlets - a l/ I 6'' stainless steel sample line -Chemical Warfare Air (CW Air) or a ground probe with enclosed capillary currently in use by the US Army - CW Ground. The Block II design is capable of both electron ionization and chemical ionization. Ethanol is being used as the Cl reagent based on a study indicating best performance for the Biological Warfare (BW) detection task (31). Data showing good signal to noise for 500 pg of methyl salicylate injected into the CW Air inlet, 50 ng of dimethylmethylphosphonate exposed to the CW Ground probe and 5 ng of methyl stearate analyzed using the pyrolyzer inlet were presented. Biological agents are sampled using a ''bio-concentrator'' unit that is designed to concentrate particles in the low micron range. Particles are collected in the bottom of a quartz pyrolyzer tube. An automated injector is being developed to deliver approximately 2 pL of a methylating reagent, tetramethylamonium- hydroxide to 'the collected particles. Pyrolysis occurs by rapid heating to ca. 55OOC. Biological agents are then characterized by their fatty acid methyl ester profiles and by other biomarkers. A library of ETOH- Cl/ pyrolysis MS data of microorganisms used for a recently published study[3] has been

  13. Selective transport of metal ions through cation exchange membrane in the presence of a complexing agent

    Energy Technology Data Exchange (ETDEWEB)

    Tingchia Huang; Jaukai Wang (National Cheng Kung Univ., Tainan (Taiwan, Province of China))

    1993-01-01

    Selective transport of metal ions through a cation exchange membrane was studied in stirred batch dialyzer for the systems Ni[sup 2+]-Cu[sup 2+] and Cu[sup 2+]-Fe[sup 3+]. Oxalic acid, malonic acid, citric acid, glycine, and ethylenediaminetetraacetic acid were employed as the complexing agents added in the feed solution in order to increase the permselectivity of metal ions. The experimental results show that the selective transport behavior of metal ions depends on the valence and the concentration of metal ions, the stoichiometric ratio of complexing agent to metal ions, and the pH value of the feed solution, but is independent of the concentration of counterion in the stripping phase. A theoretical approach was formulated on the basis of the Nernst-Planck equation and interface quasi-equilibrium. Theoretical solutions obtained from numerical calculation were in agreement with the experimental data.

  14. Heat-resistant agent used for control sand of steam huff and puff heavy oil well

    Science.gov (United States)

    Zhang, F. S.; Liu, G. L.; Lu, Y. J.; Xiong, X. C.; Ma, J. H.; Su, H. M.

    2018-01-01

    Heat-resistant agent containing hydroxymethyl group was synthesized from coal tar, which has similar structure with phenolic resin and could improve the heat resistance of phenolic resin sand control agent. The results showed that the heat resistance of the sand control agent was improved by adding 10% to 30% heat-resistant agent, after 280°C high temperature treatment for 7d, the compressive strength of consolidated core was increased to more than 5MPa. The compressive strength of consolidation core was not decreased after immersion in formation water, crude oil, acid or alkaline medium, which showed good resistance to medium immersion. The sand control agent had small core damage and the core permeability damage ratio of sand control agent consolidation was only 18.7%.

  15. Marginal integrity of low-shrinkage and methacrylate-based composite resins: Effect of three different hemostatic agents

    Science.gov (United States)

    Khoroushi, Maryam; Sahraneshin-Samani, Mahsa

    2016-01-01

    Background Moisture control is very important in restorative procedures in dentistry. Use of hemostatic agents helps control moisture; however, they might result in changes on enamel and dentin surfaces, affecting composite resin bond quality. The aim of this in vitro study was to evaluate the marginal microleakage of two different composite resins with the use of three different hemostatic agents. Material and Methods Standardized Class V cavities were prepared on the buccal and lingual surfaces of 48 premolars with cervical margins 1 mm apical to the cementoenamel junction (CEJ). The samples were randomly divided into 8 groups. In groups 1 to 4, an etch-and-rinse adhesive (Adper Single Bond) was applied as the bonding system, followed by exposure to different hemostatic agent: group 1: no hemostatic agent (control); group 2: ViscoStat; group 3: ViscoStat Clear; and group 4: trichloracetic acid, as hemostatic agents. The cavities were restored with Z-250 composite resin. In group 5 to 8 Silorane System Adhesive (Filtek P90 Adhesive) was applied as a bonding agent, followed by exposure to different hemostatic agents in a manner similar to that in groups 1to 4. The cavities were restored with Filtek P90, a low-shrinkage composite resin. The samples in each group were evaluated for dye penetration under a stereomicroscope at ×36 after 24 hours and a 500-round thermocycling procedure at enamel and dentin margins. Statistical analysis was carried out using Kruskal-Wallis and Mann-Whitney tests (α=0.05). Results Z-250 composite resin exhibited significantly higher dentin microleakage scores compared to Filtek P90 (P = 0.004). Trichloracetic acid increased dentin microleakage with Filtek P90 (P=0.033). Conclusions Under the limitations of this in vitro study, application of hemostatic agents did not affect microleakage of the two tested composite resins except for trichloracetic acid that increased marginal microleakage when used with Filtek P90. Key words

  16. Changes in isoprenoid lipid synthesis by gemfibrozil and clofibric acid in rat hepatocytes.

    Science.gov (United States)

    Hashimoto, F; Taira, S; Hayashi, H

    2000-05-15

    We studied whether gemfibrozil and clofibric acid alter isoprenoid lipid synthesis in rat hepatocytes. After incubation of the cells with the agent for 74 hr, [(14)C]acetate or [(3)H]mevalonate was added, and the cells were further incubated for 4 hr. Gemfibrozil and clofibric acid increased ubiquinone synthesis from [(14)C]acetate and [(3)H]mevalonate. The effect of gemfibrozil was greater than that of clofibric acid. Also, gemfibrozil decreased dolichol synthesis from [(14)C]acetate and [(3)H]mevalonate. However, clofibric acid increased dolichol synthesis from [(3)H]mevalonate. Gemfibrozil decreased cholesterol synthesis from [(14)C]acetate and [(3)H]mevalonate. Clofibric acid decreased cholesterol synthesis from [(14)C]acetate, but did not affect synthesis from [(3)H]mevalonate. These results suggest that both agents, at different rates, activate the synthetic pathway of ubiquinone, at least from mevalonate. Gemfibrozil may inhibit the synthetic pathway of dolichol, at least from mevalonate. Contrary to gemfibrozil, clofibric acid may activate the synthetic pathway of dolichol from mevalonate. Gemfibrozil may inhibit the synthetic pathway of cholesterol from mevalonate in addition to the pathway from acetate to mevalonate inhibited by both agents.

  17. Hepatic handling of a synthetic gamma-labeled bile acid (75SeHCAT)

    International Nuclear Information System (INIS)

    Galatola, G.; Jazrawi, R.P.; Bridges, C.; Joseph, A.E.; Northfield, T.C.

    1988-01-01

    75 Se-homocholic acid-taurine ( 75 SeHCAT) is the first available gamma-labeled bile acid, and should therefore be handled more efficiently and specifically by the liver than previous hepatoscintigraphic agents. We have measured serum and hepatic kinetics for 75 SeHCAT, and compared them with those for the conventional hepatobiliary scintigraphic agent 99mTc-hepatoiminodiacetic acid, and with serum kinetics for the corresponding natural bile acid, [ 14 C]cholic acid-taurine. We used a dynamic scintigraphic technique and serial blood sampling in 8 subjects. Initial hepatic uptake rate was identical to initial serum disappearance rate (14% dose/min) for 75 SeHCAT, but significantly lower for 99mTc-hepatoiminodiacetic acid (6% vs. 14% dose/min, p less than 0.001). Hepatic transit time was shorter for 75 SeHCAT (13 min vs. 22 min, p less than 0.02), net hepatic excretory rate was more rapid (1.4% vs. 0.8% dose/min, p less than 0.001), and urinary excretion was lower (1.0% vs. 9.0% dose, p less than 0.001). Initial and late-plasma disappearance rates were significantly lower for 75 SeHCAT (14.3% and 1.5% dose/min) than for [ 14 C]cholic acid-taurine (21.3% and 2.8% dose/min, respectively), and plasma clearance was also lower (2 75 vs. 670 ml/min). In vitro, 75 SeHCAT was bound to serum proteins more completely than [ 14 C]cholic acid-taurine (90.4% vs. 86.5%, p less than 0.005). We conclude that 75 SeHCAT provides a hepatoscintigraphic agent that is handled more efficiently and specifically by the liver than the conventionally used agent 99mTc-hepatoiminodiacetic acid. It is not cleared from the serum as rapidly as [ 14 C]cholic acid-taurine, probably due to its stronger protein binding. The clinical value of 75 SeHCAT in assessing liver disease should be investigated

  18. Influence of bleaching agents on surface roughness of sound or eroded dental enamel specimens.

    Science.gov (United States)

    Azrak, Birgül; Callaway, Angelika; Kurth, Petra; Willershausen, Brita

    2010-12-01

    The aim of the present in vitro study was to assess the effect of bleaching agents on eroded and sound enamel specimens. Enamel specimens prepared from human permanent anterior teeth were incubated with different bleaching agents containing active ingredients as 7.5 or 13.5% hydrogen peroxide or 35% carbamide peroxide, ranging in pH from 4.9 to 10.8. The effect of the tooth whitening agents on surface roughness was tested for sound enamel surfaces as well as for eroded enamel specimens. To provoke erosive damage, the enamel specimens were incubated for 10 hours with apple juice (pH = 3.4). Afterwards, pretreated and untreated dental slices were incubated with one of the bleaching agents for 10 hours. The surface roughness (R(a)) of all enamel specimens (N = 80) was measured using an optical profilometric device. A descriptive statistical analysis of the R(a) values was performed. The study demonstrated that exposure to an acidic bleaching agent (pH = 4.9) resulted in a higher surface roughness (p = 0.043) than treatment with a high peroxide concentration (pH = 6.15). If the enamel surface was previously exposed to erosive beverages, subsequent bleaching may enhance damage to the dental hard tissue. Bleaching agents with a high concentration of peroxide or an acidic pH can influence the surface roughness of sound or eroded enamel. © 2010, COPYRIGHT THE AUTHORS. JOURNAL COMPILATION © 2010, WILEY PERIODICALS, INC.

  19. Acridone-based inhibitors of inosine 5'-monophosphate dehydrogenase: discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1-yl)pyridin-3-yl)propan-2-yl)-2- fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419).

    Science.gov (United States)

    Watterson, Scott H; Chen, Ping; Zhao, Yufen; Gu, Henry H; Dhar, T G Murali; Xiao, Zili; Ballentine, Shelley K; Shen, Zhongqi; Fleener, Catherine A; Rouleau, Katherine A; Obermeier, Mary; Yang, Zheng; McIntyre, Kim W; Shuster, David J; Witmer, Mark; Dambach, Donna; Chao, Sam; Mathur, Arvind; Chen, Bang-Chi; Barrish, Joel C; Robl, Jeffrey A; Townsend, Robert; Iwanowicz, Edwin J

    2007-07-26

    Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5'-monophosphate to xanthosine-5'-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.

  20. Current trends in immunosuppressive therapies for renal transplant recipients.

    Science.gov (United States)

    Lee, Ruth-Ann; Gabardi, Steven

    2012-11-15

    Current trends in immunosuppressive therapies for renal transplant recipients are reviewed. The common premise for immunosuppressive therapies in renal transplantation is to use multiple agents to work on different immunologic targets. The use of a multidrug regimen allows for pharmacologic activity at several key steps in the T-cell replication process and lower dosages of each individual agent, thereby producing fewer drug-related toxicities. In general, there are three stages of clinical immunosuppression: induction therapy, maintenance therapy, and treatment of an established acute rejection episode. Only immunosuppressive therapies used for maintenance therapy are discussed in detail in this review. The most common maintenance immunosuppressive agents can be divided into five classes: (1) the calcineurin inhibitors (CNIs) (cyclosporine and tacrolimus), (2) costimulation blockers (belatacept), (3) mammalian target of rapamycin inhibitors (sirolimus and everolimus), (4) antiproliferatives (azathioprine and mycophenolic acid derivatives), and (5) corticosteroids. Immunosuppressive regimens vary among transplantation centers but most often include a CNI and an adjuvant agent, with or without corticosteroids. Selection of appropriate immunosuppressive regimens should be patient specific, taking into account the medications' pharmacologic properties, adverse-event profile, and potential drug-drug interactions, as well as the patient's preexisting diseases, risk of rejection, and medication regimen. Advancements in transplant immunosuppression have resulted in a significant reduction in acute cellular rejection and a modest increase in long-term patient and graft survival. Because the optimal immunosuppression regimen is still unknown, immunosuppressant use should be influenced by institutional preference and tailored to the immunologic risk of the patient and adverse-effect profile of the drug.

  1. A gadolinium(III) complex of a carboxylic-phosphorus acid derivative of diethylenetriamine covalently bound to inulin, a potential macromolecular MRI contrast agent.

    Science.gov (United States)

    Lebdusková, Petra; Kotek, Jan; Hermann, Petr; Vander Elst, Luce; Muller, Robert N; Lukes, Ivan; Peters, Joop A

    2004-01-01

    A novel conjugate of a polysaccharide and a Gd(III) chelate with potential as contrast agent for magnetic resonance imaging (MRI) was synthesized. The structure of the chelate was derived from H5DTPA by replacing the central pendant arm by a phosphinic acid functional group, which was covalently bound to the polysaccharide inulin. On the average, each monosaccharide unit of the inulin was attached to approximately one (0.9) chelate moiety. The average molecular weight is 23110 and the average number of Gd3+ ions per molecule is 24. The ligand binds the Gd3+ ion in an octadentate fashion via three nitrogen atoms, four carboxylate oxygen atoms, and one P-O oxygen atom, and its first coordination sphere is completed by a water molecule. This compound shows promising properties for application as a contrast agent for MRI thanks to a favorable residence lifetime of this water molecule (170 ns at 298 K), a relatively long rotational correlation time (866 ps at 298 K), and the presence of two water molecules in the second coordination sphere of the Gd3+ ion. Furthermore, its stability toward transmetalation with Zn(II) is as high as that of the clinically used [Gd(DTPA)(H2O)]2-.

  2. Dermatomyositis-like syndrome induced by nonsteroidal anti-inflammatory agents.

    Science.gov (United States)

    Grob, J J; Collet, A M; Bonerandi, J J

    1989-01-01

    A dermatomyositis-like syndrome developed in a patient treated with a nonsteroidal anti-inflammatory agent (NSAI), niflumic acid, and regressed after the cessation of treatment. Previously an eruption had occurred under treatment with another NSAI, diclofenac. Our report shows that NSAI can induce not only lupus-like syndromes but also other connective tissue disorders.

  3. Radiation synthesis and characterization of polyacrylic acid hydrogels

    International Nuclear Information System (INIS)

    Yang Mingcheng; Song Hongyan; Zhu Chengshen; He Suqin

    2007-01-01

    The pH-sensitive polyacrylic acid (PAA) hydrogels were synthesized by gamma-ray irradiation at an ambient temperature. The influences of dose, monomer concentration, cross-linking agent content, pH, and ionic strength on the swelling ratio (SR) of the PAA hydrogels were investigated in detail. The results show that the SR of the hydrogel decreases with an increase in the dose, monomer concentration, and cross-linking agent content. In alkaline solution, the SR of the hydrogels is much higher than that in acid solution. Also, the ionic strength can influence the SR of the hydrogels. The more the concentration, the lower the SR. (authors)

  4. Use of psyllium (isubgol) husk as an alternative gelling agent for the ...

    African Journals Online (AJOL)

    SERVER

    2008-04-17

    Apr 17, 2008 ... of gelling agents including carrageenans (Liners et al.,. 2005), alginates .... uronic acid 3%) is soluble in hot water, forming a highly viscous solution .... Evidence for the recognition of a secondary structure of carrageenan.

  5. The outcomes of two different bulking agents (dextranomer hyaluronic acid copolymer and polyacrylate-polyalcohol copolymer in the treatment of primary vesico-ureteral reflux

    Directory of Open Access Journals (Sweden)

    Hakan Taşkinlar

    2016-06-01

    Full Text Available ABSTRACT Purpose Subureteral injection of bulking agents in the endoscopic treatment of vesicoureteral reflux is widely accepted therapy with high success rates. Although the grade of vesicoureteric reflux and experience of surgeon is the mainstay of this success, the characteristics of augmenting substances may have an effect particularly in the long term. In this retrospective study, we aimed to evaluate the clinical outcomes of the endoscopic treatment of vesicoureteric reflux (VUR with two different bulking agents: Dextranomer/hyaluronic acid copolymer (Dx/HA and Polyacrylate polyalcohol copolymer (PPC. Materials and Methods A total 80 patients (49 girls and 31 boys aged 1-12 years (mean age 5.3 years underwent endoscopic subureteral injection for correction of VUR last six years. The patients were assigned to two groups: subureteral injections of Dx/HA (45 patients and 57 ureters and PPC (35 patients and 45 ureters. VUR was grade II in 27 ureters, grade III in 35, grade IV in 22 and grade V in 18 ureters. Results VUR was resolved in 38 (66.6% of 57 ureters and this equates to VUR correction in 33 (73.3% of the 45 patients in Dx/HA group. In PPC group, overall success rate was 88.8% (of 40 in 45 ureters. Thus, Thus, this equates to VUR correction in 31 (88.5% of the 35 patients. Conclusions Our short term data show that two different bulking agent injections provide a high level of reflux resolution and this study revealed that success rate of PPC was significantly higher than Dx/HA with less material.

  6. Acid Deposition Phenomena

    International Nuclear Information System (INIS)

    Ramadan, A.E.K.

    2004-01-01

    Acid deposition, commonly known as acid rain, occurs when emissions from the combustion of fossil fuels and other industrial processes undergo complex chemical reactions in the atmosphere and fall to the earth as wet deposition (rain, snow, cloud, fog) or dry deposition (dry particles, gas). Rain and snow are already naturally acidic, but are only considered problematic when less than a ph of 5.0 The main chemical precursors leading to acidic conditions are atmospheric concentrations of sulfur dioxide (SO 2 ) and nitrogen oxides (NO x ). When these two compounds react with water, oxygen, and sunlight in the atmosphere, the result is sulfuric (H 2 SO 4 ) and nitric acids (HNO 3 ), the primary agents of acid deposition which mainly produced from the combustion of fossil fuel and from petroleum refinery. Airborne chemicals can travel long distances from their sources and can therefore affect ecosystems over broad regional scales and in locations far from the sources of emissions. According to the concern of petroleum ministry with the environment and occupational health, in this paper we will discussed the acid deposition phenomena through the following: Types of acidic deposition and its components in the atmosphere Natural and man-made sources of compounds causing the acidic deposition. Chemical reactions causing the acidic deposition phenomenon in the atmosphere. Factors affecting level of acidic deposition in the atmosphere. Impact of acid deposition. Procedures for acidic deposition control in petroleum industry

  7. Role of nitrous acid during the dissolution of UO2 in nitric acid

    International Nuclear Information System (INIS)

    Deigan, N.; Pandey, N.K.; Kamachi Mudali, U.; Joshi, J.B.

    2016-01-01

    Understanding the dissolution behaviour of sintered UO 2 pellet in nitric acid is very important in designing an industrial scale dissolution system for the plutonium rich fast reactor MOX fuel. In the current article we have established the role of nitrous acid on the dissolution kinetics of UO 2 pellets in nitric acid. Under the chemical conditions that prevail in a typical Purex process, NO and NO 2 gases gets generated in the process streams. These gases produce nitrous acid in nitric acid medium. In addition, during the dissolution of UO 2 in nitric acid medium, nitrous acid is further produced in-situ at the pellet solution interface. As uranium dissolves oxidatively in nitric acid medium wherein it goes from U(IV) in solid to U(VI) in liquid, presence of nitrous acid (a good oxidizing agent) accelerates the reaction rate. Hence for determining the reaction mechanism of UO 2 dissolution in nitric acid medium, knowing the nitrous acid concentration profile during the course of dissolution is important. The current work involves the measurement of nitrous acid concentration during the course of dissolution of sintered UO 2 pellets in 8M starting nitric acid concentration as a function of mixing intensity from unstirred condition to 1500 RPM

  8. Nutraceuticals as therapeutic agents for atherosclerosis.

    Science.gov (United States)

    Moss, Joe W E; Williams, Jessica O; Ramji, Dipak P

    2018-05-01

    Atherosclerosis, a chronic inflammatory disorder of medium and large arteries and an underlying cause of cardiovascular disease (CVD), is responsible for a third of all global deaths. Current treatments for CVD, such as optimized statin therapy, are associated with considerable residual risk and several side effects in some patients. The outcome of research on the identification of alternative pharmaceutical agents for the treatment of CVD has been relatively disappointing with many promising leads failing at the clinical level. Nutraceuticals, products from food sources with health benefits beyond their nutritional value, represent promising agents in the prevention of CVD or as an add-on therapy with current treatments. This review will highlight the potential of several nutraceuticals, including polyunsaturated fatty acids, flavonoids and other polyphenols, as anti-CVD therapies based on clinical and pre-clinical mechanism-based studies. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

  9. Effect of a novel insulinotropic agent, succinic acid monoethyl ester ...

    Indian Academy of Sciences (India)

    Madhu

    index (AAI) (ratio of HDL-C to total cholesterol) were studied. ... ester; FFA, free falty acids; HDL-C, high density lipoprotein-cholesterol; LDL-C, low density lipoprotein-cholesterol; ..... and impaired catabolism of triglyceride-rich particles. The.

  10. Magnesium hydroxide as the neutralizing agent for radioactive hydrochloric acid solutions

    International Nuclear Information System (INIS)

    Palmer, M.J.; Fife, K.W.

    1995-10-01

    The current technology at Los Alamos for removing actinides from acidic chloride waste streams is precipitation with approximately 10 M potassium hydroxide. Although successful, there are many inherent drawbacks to this precipitation technique which will be detailed in this paper. Magnesium hydroxide (K sp = 1.3 x 10 -11 ) has limited solubility in water and as a result of the common ion effect, cannot generate a filtrate with a pH greater than 9. At a pH of 9, calcium (K sp = 5.5 x 10 -6 ) will not coprecipitate as the hydroxide. This is an important factor since many acidic chloride feeds to hydroxide precipitation contain significant amounts of calcium. In addition, neutralization with Mg(OH) 2 produces a more filterable precipitate because neutralization occurs as the Mg(OH) 2 is dissolved by the acid rather than as a result of the much faster liquid/liquid reaction of KOH with the waste acid. This slower solid/liquid reaction allows time for crystal growth to occur and produces more easily filterable precipitates. On the other hand, neutralization of spent acid with strong KOH that yields numerous hydroxide ions in solution almost instantaneously forming a much larger volume of small crystallites that result in gelatinous, slow-filtering precipitates. Magnesium hydroxide also offers a safety advantage. Although mildly irritating, it is a weak base and safe and easy to handle. From a waste minimization perspective, Mg(OH) 2 offers many advantages. First, the magnesium hydroxide is added as a solid. This step eliminates the diluent water used in KOH neutralizations. Secondly, because the particle size of the precipitate is larger, more actinides are caught on the filter paper resulting in a smaller amount of actinide being transferred to the TA-50 Liquid Waste Treatment Facility. Third, the amount of solids that must be reprocessed is significantly smaller resulting in less waste generation from the downstream processes

  11. Effects of lead mineralogy on soil washing enhanced by ferric salts as extracting and oxidizing agents.

    Science.gov (United States)

    Yoo, Jong-Chan; Park, Sang-Min; Yoon, Geun-Seok; Tsang, Daniel C W; Baek, Kitae

    2017-10-01

    In this study, we evaluated the feasibility of using ferric salts including FeCl 3 and Fe(NO 3 ) 3 as extracting and oxidizing agents for a soil washing process to remediate Pb-contaminated soils. We treated various Pb minerals including PbO, PbCO 3 , Pb 3 (CO 3 ) 2 (OH) 2 , PbSO 4 , PbS, and Pb 5 (PO 4 ) 3 (OH) using ferric salts, and compared our results with those obtained using common washing agents of HCl, HNO 3 , disodium-ethylenediaminetetra-acetic acid (Na 2 -EDTA), and citric acid. The use of 50 mM Fe(NO 3 ) 3 extracted significantly more Pb (above 96% extraction) from Pb minerals except PbSO 4 (below 55% extraction) compared to the other washing agents. In contrast, washing processes using FeCl 3 and HCl were not effective for extraction from Pb minerals because of PbCl 2 precipitation. Yet, the newly formed PbCl 2 could be dissolved by subsequent wash with distilled water under acidic conditions. When applying our washing method to remediate field-contaminated soil from a shooting range that had high concentrations of Pb 3 (CO 3 ) 2 (OH) 2 and PbCO 3 , we extracted more Pb (approximately 99% extraction) from the soil using 100 mM Fe(NO 3 ) 3 than other washing agents at the same process conditions. Our results show that ferric salts can be alternative washing agents for Pb-contaminated soils in view of their extracting and oxidizing abilities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Non-infectious plasmid engineered to simulate multiple viral threat agents.

    Science.gov (United States)

    Carrera, Monica; Sagripanti, Jose-Luis

    2009-07-01

    The aim of this study was to design and construct a non-virulent simulant to replace several pathogenic viruses in the development of detection and identification methods in biodefense. A non-infectious simulant was designed and engineered to include the nucleic acid signature of VEEV (Venezuelan Equine Encephalitis virus), Influenza virus, Rift Valley Fever virus, Machupo virus, Lassa virus, Yellow Fever virus, Ebola virus, Eastern Equine Encephalitis virus, Junin virus, Marburg virus, Dengue virus, and Crimean-Congo virus, all in a single construct. The nucleic acid sequences of all isolates available for each virus species were aligned using ClustalW software in order to obtain conserved regions of the viral genomes. Specific primers were designed to permit the identification and differentiation between viral threat agents. A chimera of 3143 base pairs was engineered to produce 13 PCR amplicons of different sizes. PCR amplification of the simulant with virus-specific primers revealed products of the predicted length, in bands of similar intensity, and without detectable unspecific products by electrophoresis analysis. The simulant described could reduce the need to use infectious viruses in the development of detection and diagnostic methods, and could also be useful as a non-virulent positive control in nucleic acid-based tests against biological threat agents.

  13. Preparation of Epoxidized Palm Olein as Renewable Material by Using Peroxy Acids

    International Nuclear Information System (INIS)

    Darfizzi Derawi; Jumat Salimon; Waled Abdo Ahmed

    2014-01-01

    Epoxidized palm olein (EPO o ) was prepared through generated in situ of performic acid (HCOOOH), and peracetic acid (CH 3 COOOH) as epoxidation agent with the presence of sulphuric acid (H 2 SO 4 ) 3 % v/ wt as catalyst. Formic acid (HCOOH) or acetic acid (CH 3 COOH) as oxygen carrier and hydrogen peroxide (H 2 O 2 ) as oxygen donor in the reaction system. Highly conversion (95.5 %) of oxirane ring was obtained by using performic acid as epoxidation agent at 150 minutes of reaction time. The reaction yield was 90 % by weight. EPO o has showed good physicochemical properties as renewable material for industrial applications. Carbon ( 13 C-NMR) and proton ( 1 H-NMR) spectra showed the present of epoxy profile at 54 ppm and 2.9 ppm. Epoxy group was detected on 844 cm -1 by fourier transformation infra-red (FTIR) spectra. (author)

  14. PEGylated chitosan grafted with polyamidoaminedendron as tumor-targeted magnetic resonance imaging contrast agent

    International Nuclear Information System (INIS)

    Guangyue Zu; Xiaoyan Tong; Yi Cao; Ye Kuang; Yajie Zhang; Min Liu; Renjun Pei

    2017-01-01

    Macromolecular contrast agents labeled with targeting ligands are now receiving growing interest in tumor-targeted magnetic resonance imaging. In this study, a macromolecular contrast agent based on PEGylated chitosan was synthesized and characterized, and its application as an MRI contrast agent was then demonstrated both in vitro and in vivo. First, the chitosan backbone was partially grafted with poly(ethylene glycol), which was used to improve the in vivo stability, followed by modifying with azide groups. Second, alkynyl-terminated PAMAM dendron modified with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) was synthesized and conjugated onto the chitosan backbone through click chemistry. Finally, the obtained mCA was further functionalized with folic acid to improve the target specificity. The obtained FA labeled mCA exhibited higher relaxivity (9.53 mM"-"1.s"-"1) relative to Gd-DTPA (4.25 mM"-"1.s"-"1) and showed negligible toxicity as determined by the WST assay. In vivo MRI results suggested that a relatively high signal enhancement was observed in the tumor region, which made it a promising candidate for tumor-targeted MRI CA. (authors)

  15. The clinical use of contrast agents in magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bydder, G.M.

    1987-01-01

    Interest in the use of external agents to increase tissue contrasts has come from many sources dating back to the earliest work in NMR, to animal studies and to the widespread use of contrast agents in conventional radiological practice. The first clinical magnetic resonance images were published in 1980 and in the following year a brief account of the use of the paramagnetic agents in human volunteers was established. It was apparent relatively early in the development of magnetic resonance imaging (MRI) that a high level of soft tissue contrast was available de novo and the need for externally administered agents might therefore be small. This observation was tempered by the fact that separation of tumour from oedema was frequently better with contrast enhanced CT X-ray than with unenhanced MRI and that of a contrast agent might therefore be needed for MRI. At the end of 1983 the first parenteral agent gadoliminum diethylene triamine pentaacetic acid (Gd-DTPA) was used in volunteers and clinical studies began in 1984. At the present time only molecular O/sub 2/, oral iron compounds and Gd-DTPA are in clinical use although there are a number of other agents which have been used in animals and some of these may become available for clinical use in the foreseeable future

  16. A Potential Adjuvant Agent of Chemotherapy: Sepia Ink Polysaccharides

    Directory of Open Access Journals (Sweden)

    Fangping Li

    2018-03-01

    Full Text Available Sepia ink polysaccharide (SIP isolated from squid and cuttlefish ink is a kind of acid mucopolysaccharide that has been identified in three types of primary structures from squid (Illex argentinus and Ommastrephes bartrami, cuttlefish Sepiella maindroni, and cuttlefish Sepia esculenta ink. Although SIP has been proved to be multifaceted, most of the reported evidence has illuminated its chemopreventive and antineoplastic activities. As a natural product playing a role in cancer treatment, SIP may be used as chemotherapeutic ancillary agent or functional food. Based on the current findings on SIP, we have summarized four topics in this review, including: chemopreventive, antineoplastic, chemosensitive, and procoagulant and anticoagulant activities, which are correlative closely with the actions of anticancer agents on cancer patients, such as anticancer, toxicity and thrombogenesis, with the latter two actions being common causes of death in cancer cases exposed to chemotherapeutic agents.

  17. Emulsion Liquid Membrane Technology in Organic Acid Purification

    International Nuclear Information System (INIS)

    Norela Jusoh; Norasikin Othman; Nur Alina Nasruddin

    2016-01-01

    Emulsion Liquid Membrane (ELM) process have shown a great potential in wide application of industrial separations such as in removal of many chemicals, organic compounds, metal ions, pollutants and biomolecules. This system promote many advantages including simple operation, high selectivity, low energy requirement, and single stage extraction and stripping process. One potential application of ELM is in the purification of succinic acid from fermentation broth. This study outline steps for developing emulsion liquid membrane process in purification of succinic acid. The steps include liquid membrane formulation, ELM stability and ELM extraction of succinic acid. Several carrier, diluent and stripping agent was screened to find appropriate membrane formulation. After that, ELM stability was investigated to enhance the recovery of succinic acid. Finally, the performance of ELM was evaluated in the extraction process. Results show that formulated liquid membrane using Amberlite LA2 as carrier, palm oil as diluent and sodium carbonate, Na_2CO_3 as stripping agent provide good performance in purification. On the other hand, the prepared emulsion was observed to be stable up to 1 hour and sufficient for extraction process. In conclusion, ELM has high potential to purify succinic acid from fermentation broth. (author)

  18. Swelling and tensile properties of starch glycerol system with various crosslinking agents

    Science.gov (United States)

    Mohamed, R.; Mohd, N.; Nurazzi, N.; Siti Aisyah, M. I.; Fauzi, F. Mohd

    2017-07-01

    Brittle properties of starch had been overcome by the modification process. In this work, sago starch is being modified with variable amount of plasticiser, namely glycerol at 20 and 40% and crosslinking agent had been added to the system. The film of the modification and characterizations of the starch glycerol system with various crosslinking systems were produced by casting method. The film properties of the starch glycerol system were then characterized by tensile strength (mechanical properties) and swelling (physical properties). The modification of the starch glycerol had improved that system by increasing the tensile strength, modulus however lowering its elongation. The increasing in percentage of the water absorption and also swelling are due to the intrinsic hydroxyl groups presence from the starch and glycerol itself that can attract more water to the system. Upon crosslinking, films casted with chemicals namely, glyoxal, malonic acid, borax, PEG were characterised. It was found that, all the film of sago starch crosslinked and undergoing easy film formation. From this modification, borax and malonic acid crosslinking agent had been determined as the best crosslinking agent to the starch glycerol system.

  19. A review on common chemical hemostatic agents in restorative dentistry

    Directory of Open Access Journals (Sweden)

    Pardis Tarighi

    2014-01-01

    Full Text Available Control of hemorrhage is one of the challenging situations dentists confront during deep cavity preparation and before impressions or cementation of restorations. For the best bond and least contamination it is necessary to be familiar with the hemostatic agents available on the market and to be able to choose the appropriate one for specific situations. This review tries to introduce the commercially available hemostatic agents, discusses their components and their specific features. The most common chemical agents that are widely used in restorative and prosthodontic dentistry according to their components and mechanism of action as well as their special uses are introduced. PubMed and Google Scholar were searched for studies involving gingival retraction and hemostatic agents from 1970 to 2013. Key search words including: "gingival retraction techniques, impression technique, hemostasis and astringent" were searched. Based on the information available in the literature, in order to achieve better results with impression taking and using resin bonding techniques, common hemostatic agents might be recommended before or during acid etching; they should be rinsed off properly and it is recommended that they be used with etch-and-rinse adhesive systems.

  20. Comparison of in vitro activity of undecylenic acid and tolnaftate against athlete's foot fungi.

    Science.gov (United States)

    Amsel, L P; Cravitz, L; VanderWyk, R; Zahry, S

    1979-03-01

    Undecylenic acid and tolnaftate were tested in an in vitro test system to evaluate their relative "killing time" efficacy against Trichophyton mentagrophytes, Trichophyton rubrum, and Epidermophyton floccosum. Commercial products containing these active agents were tested similarly. The pure active agents were equivalent in activity. The commercial product containing undecylenic acid appeared to be more effective against the test organisms than did the product containing tolnaftate.

  1. L-β-N-methylamino-l-alanine (BMAA) nitrosation generates a cytotoxic DNA damaging alkylating agent: An unexplored mechanism for neurodegenerative disease.

    Science.gov (United States)

    Potjewyd, G; Day, P J; Shangula, S; Margison, G P; Povey, A C

    2017-03-01

    L-β-N-methylamino-l-alanine (BMAA) is a non-proteinic amino acid, that is neurotoxic in vitro and in animals, and is implicated in the causation of amyotrophic lateral sclerosis and parkinsonism-dementia complex (ALS-PDC) on Guam. Given that natural amino acids can be N-nitrosated to form toxic alkylating agents and the structural similarity of BMAA to other amino acids, our hypothesis was that N-nitrosation of BMAA might result in a toxic alkylating agent, providing a novel mechanistic hypothesis for BMAA action. We have chemically nitrosated BMAA with sodium nitrite to produce nitrosated BMAA (N-BMAA) which was shown to react with the alkyl-trapping agent, 4-(p-nitrobenzyl)pyridine, cause DNA strand breaks in vitro and was toxic to the human neuroblastoma cell line SH-SY5Y under conditions in which BMAA itself was minimally toxic. Our results indicate that N-BMAA is an alkylating agent and toxin suggesting a plausible and previously unrecognised mechanism for the neurotoxic effects of BMAA. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Nucleic Acid Therapy: from humble beginnings a dynamic technology

    CSIR Research Space (South Africa)

    Millroy, L

    2011-02-01

    Full Text Available The term “nucleic acid therapy” encompasses a wide range of technologies for the treatment of a range of plant and animal ailments. As the name implies, it makes use of nucleic acid (either DNA or RNA) as a therapeutic agent. There are six branches...

  3. Hit discovery of Mycobacterium tuberculosis inosine 5'-monophosphate dehydrogenase, GuaB2, inhibitors.

    Science.gov (United States)

    Sahu, Niteshkumar U; Singh, Vinayak; Ferraris, Davide M; Rizzi, Menico; Kharkar, Prashant S

    2018-04-18

    Tuberculosis remains a global concern. There is an urgent need of newer antitubercular drugs due to the development of resistant forms of Mycobacterium tuberculosis (Mtb). Inosine 5'-monophosphate dehydrogenase (IMPDH), guaB2, of Mtb, required for guanine nucleotide biosynthesis, is an attractive target for drug development. In this study, we screened a focused library of 73 drug-like molecules with desirable calculated/predicted physicochemical properties, for growth inhibitory activity against drug-sensitive MtbH37Rv. The eight hits and mycophenolic acid, a prototype IMPDH inhibitor, were further evaluated for activity on purified Mtb-GuaB2 enzyme, target selectivity using a conditional knockdown mutant of guaB2 in Mtb, followed by cross-resistance to IMPDH inhibitor-resistant SRMV2.6 strain of Mtb, and activity on human IMPDH2 isoform. One of the hits, 13, a 5-amidophthalide derivative, has shown growth inhibitory potential and target specificity against the Mtb-GuaB2 enzyme. The hit, 13, is a promising molecule with potential for further development as an antitubercular agent. Copyright © 2018 Elsevier Ltd. All rights reserved.

  4. Synthesis and evaluation of new protecting agents against ionizing radiations; Synthese et evaluation de nouveaux agents de protection contre les rayonnements ionisants

    Energy Technology Data Exchange (ETDEWEB)

    Nadal, B.

    2009-10-15

    This thesis is devoted to the synthesis of new pulvinic acid derivatives and the evaluation of their antioxidant and radioprotective properties. This study has been conducted with the aim to develop new protecting agents against ionizing radiations. A new access to pulvinic acid derivatives was developed starting from L-dimethyl tartrate. It is based on a Dieckmann cyclization a dehydration and a Suzuki-Miyaura coupling. It allows a short effective preparation of various pulvinic acid derivatives: tetronic acid derivatives, mono-substituted pulvinic acid derivatives and methyl pulvinates. A modified method has been used to prepare pulvinones. This strategy gave access in four steps to the desired pulvinones. The rapidity of this method is provided by a tandem process, carried out in the final step, involving a Dieckmann cyclization and a {beta}-elimination. A synthesis of 3-aryltetramic acids has also been developed in order to prepare nitrogen derivatives of pulvinic acid. The antioxidant activity of the prepared compounds was then evaluated using various tests: DPPH, ABTS, protection of thymidine and DNA study of lipid peroxidation. These evaluations allowed to define interesting structure-activity relationships of pulvinic derivatives. They have shown that several derivatives have very good antioxidant activities. Finally, radioprotective tests on TK6 cells and mice have have been performed on selected compounds. (author)

  5. Current and Emerging Topical Antibacterials and Antiseptics: Agents, Action, and Resistance Patterns.

    Science.gov (United States)

    Williamson, Deborah A; Carter, Glen P; Howden, Benjamin P

    2017-07-01

    Bacterial skin infections represent some of the most common infectious diseases globally. Prevention and treatment of skin infections can involve application of a topical antimicrobial, which may be an antibiotic (such as mupirocin or fusidic acid) or an antiseptic (such as chlorhexidine or alcohol). However, there is limited evidence to support the widespread prophylactic or therapeutic use of topical agents. Challenges involved in the use of topical antimicrobials include increasing rates of bacterial resistance, local hypersensitivity reactions (particularly to older agents, such as bacitracin), and concerns about the indiscriminate use of antiseptics potentially coselecting for antibiotic resistance. We review the evidence for the major clinical uses of topical antibiotics and antiseptics. In addition, we review the mechanisms of action of common topical agents and define the clinical and molecular epidemiology of antimicrobial resistance in these agents. Moreover, we review the potential use of newer and emerging agents, such as retapamulin and ebselen, and discuss the role of antiseptic agents in preventing bacterial skin infections. A comprehensive understanding of the clinical efficacy and drivers of resistance to topical agents will inform the optimal use of these agents to preserve their activity in the future. Copyright © 2017 American Society for Microbiology.

  6. Magnetic Resonance Imaging of Therapy-Induced Necrosis Using Gadolinium-Chelated Polyglutamic Acids

    International Nuclear Information System (INIS)

    Jackson, Edward F.; Esparza-Coss, Emilio; Wen Xiaoxia; Ng, Chaan S.; Daniel, Sherita L.; Price, Roger E.; Rivera, Belinda; Charnsangavej, Chusilp; Gelovani, Juri G.; Li Chun

    2007-01-01

    Purpose: Necrosis is the most common morphologic alteration found in tumors and surrounding normal tissues after radiation therapy or chemotherapy. Accurate measurement of necrosis may provide an early indication of treatment efficacy or associated toxicity. The purpose of this report is to evaluate the selective accumulation of polymeric paramagnetic magnetic resonance (MR) contrast agents-gadolinium p-aminobenzyl-diethylenetriaminepentaacetic acid-poly(glutamic acid) (L-PG-DTPA-Gd and D-PG-DTPA-Gd)-in necrotic tissue. Methods and Materials: Two different solid tumor models, human Colo-205 xenograft and syngeneic murine OCA-1 ovarian tumors, were used in this study. Necrotic response was induced by treatment with poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL). T 1 -weighted spin-echo images were obtained immediately and up to 4 days after contrast injection and compared with corresponding histologic specimens. Two low-molecular-weight contrast agents, DTPA-Gd and oligomeric(L-glutamic acid)-DTPA-Gd, were used as nonspecific controls. Results: Initially, there was minimal tumor enhancement after injection of either L-PG-DTPA-Gd or D-PG-DTPA-Gd, but rapid enhancement after injection of low-molecular-weight agents. However, polymeric contrast agents, but not low-molecular-weight contrast agents, caused sustained enhancement in regions of tumor necrosis in both tumors treated with PG-TXL and untreated tumors. These data indicate that high molecular weight, rather than in vivo biodegradation, is necessary for the specific localization of polymeric MR contrast agents to necrotic tissue. Moreover, biotinylated L-PG-DTPA-Gd colocalized with macrophages in the tumor necrotic areas, suggesting that selective accumulation of L- and D-PG-DTPA-Gd in necrotic tissue was mediated through residing macrophages. Conclusions: Our data suggest that MR imaging with PG-DTPA-Gd may be a useful technique for noninvasive characterization of treatment-induced necrosis

  7. Eco-friendly Crosslinking Agent for Acid Functional Acrylic Resin

    Directory of Open Access Journals (Sweden)

    Archana Shah

    2009-01-01

    Full Text Available Oil from J. multifida was extracted and it was first converted into N,N-bis(2-hydroxyethyl Jatropha fatty amide (HEJFA. HEJFA has been synthesized by reaction between Jatropha oil and diethanol amine in presence of zinc oxide as a catalyst. The reaction is relatively rapid and proceeded to high yield at 200±5 OC. The resulting HEJFA was used to formulate thermosetting coating compositions. Films were cured at ambient (air drying and elevated (stove drying temperatures using N, N-bis(2-hydroxyethyl Jatropha fatty amide (HEJFA as eco-friendly crosslinking agent for acrylic resin. The coating performance of the various compositions was tested by measurement of scratch hardness, impact strength and chemical resistance. The results show better performance of the HEJFA based compositions compared to butylated melamine formaldehyde (MF based compositions.

  8. Extrudates of starch-xanthan gum mixtures as affected by chemical agents and irradiation

    International Nuclear Information System (INIS)

    Hanna, M.A.; Chinnaswamy, R.; Gray, D.R.; Miladinov, V.D.

    1997-01-01

    Mixtures of starch, xanthan gum and either polyvinyl alcohol, epichlorohydrin, valeric acid or adipoyl chloride were extruded. Properties of extrudates including apparent viscosity, water solubility, water absorption indices and extrudate expansion were measured for different proportions of xanthan gum, 70% amylose starch (with or without irradiation) and chemical agents. Extrusion with chemical agents and irradiation changed physical properties of both starch and xanthan gum. Expansions of extrudates were higher than that of starch. Viscosity of extrudates increased with xanthan gum concentration. The addition of 1% (w/w) polyvinyl alcohol had the greatest effect of the chemical agents. Irradiation increased the apparent viscosity of starch-xanthan gum mixtures

  9. In vitro susceptibility of Helicobacter pullorum strains to different antimicrobial agents.

    Science.gov (United States)

    Ceelen, Liesbeth; Decostere, Annemie; Devriese, Luc A; Ducatelle, Richard; Haesebrouck, Freddy

    2005-01-01

    The in vitro activity of 13 antimicrobial agents against 23 Helicobacter pullorum strains from poultry (21) and human (two) origin, and one human H. canadensis strain was tested by the agar dilution method. With the H. pullorum strains, monomodal distributions of Minimum Inhibitory Concentrations (MICs) were seen with lincomycin, doxycycline, gentamicin, tobramycin, erythromycin, tylosin, metronidazole, and enrofloxacin in concentration ranges considered as indicating susceptibility in other bacteria. The normal susceptibility level for nalidixic acid was situated at or slightly above the MIC breakpoints proposed for Campylobacteriaceae. Ampicillin, ceftriaxone, and sulphamethoxazole-trimethoprim showed poor activity against H. pullorum. For the H. canadensis strain, a similar susceptibility pattern was seen, except for nalidixic acid and enrofloxacin, whose MIC of >512 and 8 microg/ml, respectively, indicated resistance of this agent. With spectinomycin, a bimodal distribution of the MICs was noted for the tested strains; eight H. pullorum isolates originating from one flock showed acquired resistance (MIC>512 microg/ml).

  10. Agent Programming Languages and Logics in Agent-Based Simulation

    DEFF Research Database (Denmark)

    Larsen, John

    2018-01-01

    and social behavior, and work on verification. Agent-based simulation is an approach for simulation that also uses the notion of agents. Although agent programming languages and logics are much less used in agent-based simulation, there are successful examples with agents designed according to the BDI...

  11. Supercapacitive transport of pharmacologic agents using nanoporous gold electrodes.

    Science.gov (United States)

    Gittard, Shaun D; Pierson, Bonnie E; Ha, Cindy M; Wu, Chung-An Max; Narayan, Roger J; Robinson, David B

    2010-02-01

    In this study, nanoporous gold supercapacitors were produced by electrochemical dealloying of gold-silver alloy. Scanning electron microscopy and energy dispersive X-ray spectroscopy confirmed completion of the dealloying process and generation of a porous gold material with approximately 10 nm diameter pores. Cyclic voltammetry and chronoamperometry of the nanoporous gold electrodes indicated that these materials exhibited supercapacitor behavior. The storage capacity of the electrodes measured by chronoamperometry was approximately 3 mC at 200 mV. Electrochemical storage and voltage-controlled delivery of two model pharmacologic agents, benzylammonium and salicylic acid, was demonstrated. These results suggest that capacitance-based storage and delivery of pharmacologic agents may serve as an alternative to conventional drug delivery methods.

  12. Decarboxylative Trifluoromethylation of Aliphatic Carboxylic Acids.

    Science.gov (United States)

    Kautzky, Jacob A; Wang, Tao; Evans, Ryan W; MacMillan, David W C

    2018-05-14

    Herein we disclose an efficient method for the conversion of carboxylic acids to trifluoromethyl groups via the combination of photoredox and copper catalysis. This transformation tolerates a wide range of functionality including heterocycles, olefins, alcohols, and strained ring systems. To demonstrate the broad potential of this new methodology for late-stage functionalization, we successfully converted a diverse array of carboxylic acid-bearing natural products and medicinal agents to the corresponding trifluoromethyl analogues.

  13. Development of Tc99m-Saccharic Acid for Heart Imaging

    International Nuclear Information System (INIS)

    Shafii Khamis; Mohd Azfar Adenan; Bohari Yaacob; Amir Fitri Shafii

    2014-01-01

    Cardiovascular disease especially the coronary heart disease (CHD) is the leading cause of death worldwide. Coronary heart disease is a common term for the buildup of plaque in the heart coronary arteries that could block the blood supply to the myocardial and this could lead to heart attack. An estimated 17 million people died from cardiovascular disease in 2008 representing 30% of all global death. In United Kingdom, coronary heart disease killed as much as 82,000 people each year. Hence, early detection of the coronary heart disease is very important in reducing the mortality among the world population. One of the most sensitive detection methods is by radioimaging using Technetium-99m radiopharmaceuticals. Several different radio imaging agents such as Tc99m radiopharmaceutical were developed as radiagnostic agent in determining the CHD especially in identifying the blockage of the coronary artery of the heart muscle. Despite the success of Tc99m-sestamibi and Tc99m-tetrofosmin as effective agents for myocardial perfusion study, the search for other Tc99m heart imaging agents has never been interrupted. This report described the formulation of the Tc99m-saccharic acid radiopharmaceutical kit, radiolabelling of the kit, radiochemical purity evaluation of the Tc99m labeled saccharaic acid, and animal study involving radio imaging using gamma camera. The animal are then sacrificed and the biological distribution of the Tc99m-saccharic acid in-vivo was determined. Comparative study was also conducted using commercially available Tc99m-tetrafosmin, a CHD radiopharmaceutical kit. The Tc99m-saccharic acid developed gave a very high labeling efficiency of >92% with Tc99m and good uptake in the heart muscle. The saccharic acid kit developed was also found to be comparable in quality to the commercially available Tc99-tetrafosmin kit. (author)

  14. Synthesis Of Gd-dtpa-folat For Magnetic Resonance Imaging Contrast Agent And Characterization By Using 153gd-dtpa-folate Radioactive

    OpenAIRE

    G., Adang H; S., Yono; Maskur

    2012-01-01

    Contrast agent was used to clarify the image of the organ that is difficult to distinguish by MRI (Magnetic Resonance Imaging) techniques, particularly in soft tissues of the central nervous system, liver, digestive system, lymphatic system, breast, cardiovascular and pulmonary systems. One of the commonly used contrast agents in hospitals is Gadolinium-DieThylenetriamine Pentaacetic Acid (Gd-DTPA). Gd-DTPA is non specific contrast agent, therefore it has led to develop a contrast agent that ...

  15. Method of gradual acid leaching of uranium ores of silicate and aluminosilicate nature

    International Nuclear Information System (INIS)

    Bosina, B.; Krepelka, J.; Urban, P.; Kropacek, J.; Stransky, J.

    1987-01-01

    Leaching uranium ore pulp is divided into two stages. The first stage takes place without any addition of a leaching agent at elevated pressure and temperature. In the second stage, sulfuric acid is added to the pulp (50 to 1000 kg per tonne of ore) or an oxidation agent. Leaching then proceeds according to routine procedures. The procedure is used to advantage for silicate or aluminosilicate ores which contain uranium minerals which are difficult to leach, pyrite and reducing substances. The two stage leaching allows to use the technology of pressure leaching, reduces consumption of sulfuric acid and oxidation agents and still achieves the required reduction oxidation potential. (E.S.)

  16. Gene Targeting and Expression Modulation by Peptide Nucleic Acids (PNA)

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2010-01-01

    Peptide nucleic acids (PNA) are artificial structural mimics of nucleic acids capable of sequence specific hybridization to both RNA and DNA. Thus they have obvious potential as gene targeting agents for drug discovery approaches. An overview with emphasis on recent progress on RNA "interference...

  17. A systematic review of filler agents for aesthetic treatment of HIV facial lipoatrophy (FLA).

    Science.gov (United States)

    Jagdeo, Jared; Ho, Derek; Lo, Alex; Carruthers, Alastair

    2015-12-01

    HIV facial lipoatrophy (FLA) is characterized by facial volume loss. HIV FLA affects the facial contours of the cheeks, temples, and orbits, and is associated with social stigma. Although new highly active antiretroviral therapy medications are associated with less severe FLA, the prevalence of HIV FLA among treated individuals exceeds 50%. The goal of our systematic review is to examine published clinical studies involving the use of filler agents for aesthetic treatment of HIV FLA and to provide evidence-based recommendations based on published efficacy and safety data. A systematic review of the published literature was performed on July 1, 2015, on filler agents for aesthetic treatment of HIV FLA. Based on published studies, poly-L-lactic acid is the only filler agent with grade of recommendation: B. Other reviewed filler agents received grade of recommendation: C or D. Poly-L-lactic acid may be best for treatment over temples and cheeks, whereas calcium hydroxylapatite, with a Food and Drug Administration indication of subdermal implantation, may be best used deeply over bone for focal enhancement. Additional long-term randomized controlled trials are necessary to elucidate the advantages and disadvantages of fillers that have different biophysical properties, in conjunction with cost-effectiveness analysis, for treatment of HIV FLA. Published by Elsevier Inc.

  18. Agents unleashed a public domain look at agent technology

    CERN Document Server

    Wayner, Peter

    1995-01-01

    Agents Unleashed: A Public Domain Look at Agent Technology covers details of building a secure agent realm. The book discusses the technology for creating seamlessly integrated networks that allow programs to move from machine to machine without leaving a trail of havoc; as well as the technical details of how an agent will move through the network, prove its identity, and execute its code without endangering the host. The text also describes the organization of the host's work processing an agent; error messages, bad agent expulsion, and errors in XLISP-agents; and the simulators of errors, f

  19. Review of new insights into antimicrobial agents.

    Science.gov (United States)

    Dehghan Esmatabadi, M J; Bozorgmehr, A; Hajjari, S N; Sadat Sombolestani, A; Malekshahi, Z V; Sadeghizadeh, M

    2017-02-28

    People have known the bacteria and have used various ways to deal with them, from a long time ago. Perhaps, natural antibiotics with have been the first step in fighting against pathogens. However, several factors, such as dealing with unfamiliar bacteria or emergence of drug-resistant species, have motivated us to discover new antibiotics or  even change previous types. In this regard, a variety of natural and synthetic antibiotics with different origins, mechanism of action, structures and functional spectrum, have been developed and used. Some impact on the synthesis of nucleic acids and some affect protein synthesis so destroy bacteria. There is a ring in the structure of most of the antibiotics which gives them special properties. However, despite their numerous advantages, antibiotics also have drawbacks ehich limit their use in all situations. Therefore, other approaches such as photodynamic therapy (PDT) and antibacterial peptides were considered as alternatives. Photodynamic therapy (PDT) is a treatment that uses photosensitizing agents, along with light, to kill bacteria. The photosensitizing agents only work after they have been activated by certain kinds of light. Antibacterial peptides are a unique and diverse group of molecules which have  between 12 and 50 amino acids in general.  In this paper, will reviewt hree mentioned topics, namely antibiotics, photodynamic therapy and antibacterial peptides and will discuss the advantages and disadvantages of each approach briefly.

  20. Influence of complexing agents on the mechanical performances of the cement conditioning matrix

    International Nuclear Information System (INIS)

    Nicu, M.; Mihai, F.; Turcanu, C.

    1998-01-01

    The safety of the radioactive waste disposal is a priority demand concerning the protection of the environment and population. For this reason, an engineering multi-barrier system is studied in order to be improved. This study aims to establish the influence of the complexing agents on the mechanical performances of the cement conditioning matrix. Radioactive effluents which contain agents as oxalic and citric acids are generated during the radioactive decontamination operation using chemical methods. The conditioning of these wastes by cementing process imposed the experimental determination of the mechanical performances of the matrix and the upper permissible level of complexing agent concentration. To determine the influence of complexing agents on the mechanical performances of cement conditioning matrix, cubic samples (20 mm x 20 mm x 20 mm) were prepared using commercial Portland cement and solutions of organic complexing acids or salts (citric acid, oxalic acid, tartaric acid, sodium citrate and ammonium oxalate). The complexation concentration varied between 0.25% and 1% in distilled and drinking water, respectively. The selected cement/water ratio was 0.5. The experiments were focused on: - establishing the firmness of the Pa 35 cement pastes and mortars in dependence on the water/cement ratio, by classical methods (Tetmeyer probe for pastes and standard cone for mortars) and by triclinic time through a funnel with 15 mm aperture; - studying the influence of the tartaric, oxalic, citric acids, ammonium oxalate and sodium citrate solution concentrations on water quantities used to obtain pastes with normal firmness and on Pa 35 cement setting; - the influence of oxalic acid, tartaric acid and ammonium oxalate solution concentrations on the strength of compression of the pastes with normal firmness; - for testing, standard test bar cubes with 20 mm sides were used and the strength of compression was tested at 28 days; - establishing the behaviour in time of

  1. Synthesis And Characterization Of An Ion Imprinted Polymer For Cadmium Using Quinaldic Acid As Complexing Agent And Applying By Microwave

    Directory of Open Access Journals (Sweden)

    Asmawati

    2015-01-01

    Full Text Available Abstract A Cd2 Ion Imprinted Polymer Cd-IIP has been synthesized by copolymerizaton of cadmium ion quinaldic acid complexing agent 4-vynil pyridine monomer dimethyl sulfoxide solvent ethyleneglycoldimethacrylate EGDMA cross-linker and 22-azobis-isobutyronitrile AIBN initiator. Polymerization was conducted using a microwave at a temperature of 70 oC with heating times of 45 minutes. The template Cd2 was removed by leaching the template with ethanol and 4 M HCl washed by aquabidest and dried in an oven at the temperature of 60oC. The polymer particles imprinted and nonimprinted were characterized using fourir transform infrared FTIR spectroscopy scanning electron microscopy SEM and energy dispersive spectroscopy EDS. The result showed that using heating time 45 minutes at temperature 70 oC the particle morphology is viewed like as the large homogeneous. So the imprinted polymer had bands at 3483 cm-1 1726 cm-1 and 1155 cm-1 indicating the presence of OH CO and C-O respectively.

  2. Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

    Science.gov (United States)

    Chen, Zhijin; Yu, Dexin; Wang, Shaojie; Zhang, Na; Ma, Chunhong; Lu, Zaijun

    2009-07-01

    Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid-polyethylene glycol/gadolinium-diethylenetriamine-pentaacetic acid (PLA-PEG/Gd-DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA-PEG/Gd-DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA-PEG nanoparticles and the commercial contrast agent, Gd-DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA-PEG/Gd-DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was -12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA-PEG/Gd-DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed ( r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd-DTPA. PLA-PEG/Gd-DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA-PEG/Gd-DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent.

  3. A short history of anti-rheumatic therapy - VII. Biological agents

    Directory of Open Access Journals (Sweden)

    B. Gatto

    2011-11-01

    Full Text Available The introduction of biological agents has been a major turning-point in the treatment of rheumatic diseases, particularly in rheumatoid arthritis. This review describes the principle milestones that have led, through the knowledge of the structure and functions of nucleic acids, to the development of production techniques of the three major families of biological agents: proteins, monoclonal antibodies and fusion proteins. A brief history has also been traced of the cytokines most involved in the pathogenesis of inflammatory rheumatic diseases (IL-1 and TNF and the steps which have led to the use of the main biological drugs in rheumatology: anakinra, infliximab, adalimumab, etanercept and rituximab.

  4. Miracle Fruit (Synsepalum dulcificum Exhibits as a Novel Anti-Hyperuricaemia Agent

    Directory of Open Access Journals (Sweden)

    Yeu-Ching Shi

    2016-01-01

    Full Text Available Miracle fruit (Synsepalum dulcificum belongs to the Sapotaceae family. It can change flavors on taste buds, transforming acidic tastes to sweet. We evaluated various miracle fruit extracts, including water, butanol, ethyl acetate (EA, and hexane fractions, to determine its antioxidant effects. These extracts isolated from miracle fruit exerted potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodiumurate (MSU-treated RAW264.7 macrophages. Moreover, we also found that the butanol extracts of miracle fruit attenuated oxonic acid potassium salt-induced hyperuricaemia in ICR mice by lowering serum uric acid levels and activating hepatic xanthine oxidase. These effects were equal to those of allopurinol, suggesting that the butanol extract of miracle fruit could be developed as a novel anti-hyperuricaemia agent or health food.

  5. Development of membranes of PLGA functionalized with antimicrobial agents nanostructured; Desenvolvimento de membranas de PLGA funcionalizadas com agentes antimicrobianos nanoestruturados

    Energy Technology Data Exchange (ETDEWEB)

    Souza, S.G.; Molin, M.L.A.L.; Nogueira, A.L.; Schneider, E. Duek; Pezzin, A.P.T., E-mail: suelengdesouza@gmail.com [Universidade da Regiao de Joinville (UNIVILLE), SC (Brazil)

    2016-07-01

    Periodontitis is a disease affecting the tooth supporting tissues, causing loss of bone attachment. One of the possible treatments is through guided tissue regeneration (GTR). Currently, a variety of resorbable membranes are available as alternative to conventional non-resorbable membranes for this application, as the membranes of poly (lactic acid-co-glycolic acid) (PLGA). In this context, this study aimed to produce membranes were biocompatible and nanostructured functionalized with antibacterial agents and evaluate its thermal properties for future application in RTG. For the production of membranes were used as the PLGA polymer matrix. The NpAg were used at concentrations of 5, 7, 8 and 10 ppm and NpZnO were: 10, 50, 100 and 150 ppm. The materials were characterized by TGA and DSC. (author)

  6. Iron-chelating agents never suppress Fenton reaction but participate in quenching spin-trapped radicals

    International Nuclear Information System (INIS)

    Li Linxiang; Abe, Yoshihiro; Kanagawa, Kiyotada; Shoji, Tomoko; Mashino, Tadahiko; Mochizuki, Masataka; Tanaka, Miho; Miyata, Naoki

    2007-01-01

    Hydroxyl radical formation by Fenton reaction in the presence of an iron-chelating agent such as EDTA was traced by two different assay methods; an electron spin resonance (ESR) spin-trapping method with 5,5-dimethyl-1-pyrroline N-oxide (DMPO), and high Performance liquid chromatography (HPLC)-fluorescence detection with terephthalic acid (TPA), a fluorescent probe for hydroxyl radicals. From the ESR spin-trapping measurement, it was observed that EDTA seemed to suppress hydroxyl radical formation with the increase of its concentration. On the other hand, hydroxyl radical formation by Fenton reaction was not affected by EDTA monitored by HPLC assay. Similar inconsistent effects of other iron-chelating agents such as nitrylotriacetic acid (NTA), diethylenetriamine penta acetic acid (DTPA), oxalate and citrate were also observed. On the addition of EDTA solution to the reaction mixture 10 min after the Fenton reaction started, when hydroxyl radical formation should have almost ceased but the ESR signal of DMPO-OH radicals could be detected, it was observed that the DMPO-OH· signal disappeared rapidly. With the simultaneous addition of Fe(II) solution and EDTA after the Fenton reaction ceased, the DMPO-OH· signal disappeared more rapidly. The results indicated that these chelating agents should enhance the quenching of [DMPO-OH]· radicals by Fe(II), but they did not suppress Fenton reaction by forming chelates with iron ions

  7. Mobile Agent Data Integrity Using Multi-Agent Architecture

    National Research Council Canada - National Science Library

    McDonald, Jeffrey

    2004-01-01

    .... Security issues for mobile agents continue to produce research interest, particularly in developing mechanisms that guarantee protection of agent data and agent computations in the presence of malicious hosts...

  8. Demonstration of spread-on peel-off consumer products for sampling surfaces contaminated with pesticides and chemical warfare agent signatures.

    Science.gov (United States)

    Behringer, Deborah L; Smith, Deborah L; Katona, Vanessa R; Lewis, Alan T; Hernon-Kenny, Laura A; Crenshaw, Michael D

    2014-08-01

    A terrorist attack using toxic chemicals is an international concern. The utility of rubber cement and latex body paint as spray-on/spread-on peel-off collection media for signatures attributable to pesticides and chemical warfare agents from interior building and public transportation surfaces two weeks post-deposition is demonstrated. The efficacy of these media to sample escalator handrail, stainless steel, vinyl upholstery fabric, and wood flooring is demonstrated for two pesticides and eight chemicals related to chemical warfare agents. The chemicals tested are nicotine, parathion, atropine, diisopropyl methylphosphonate, dimethyl methylphosphonate, dipinacolyl methylphosphonate, ethyl methylphosphonic acid, isopropyl methylphosphonic acid, methylphosphonic acid, and thiodiglycol. Amounts of each chemical found are generally greatest when latex body paint is used. Analytes with low volatility and containing an alkaline nitrogen or a sulfur atom (e.g., nicotine and parathion) usually are recovered to a greater extent than the neutral phosphonate diesters and acidic phosphonic acids (e.g., dimethyl methylphosphonate and ethyl methylphosphonic acid). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Identification of amino acids in Securigera securidaca, a popular medicinal herb in Iranian folk medicine

    Directory of Open Access Journals (Sweden)

    S.E. Sadat-Ebrahimi

    2014-01-01

    Full Text Available Securigera securidaca (L. Degen & Dorfl grows in different parts of Iran. The seeds of the species are used in Iranian folk medicine as an anti-diabetic agent. Many studies have established hypoglycemic effects of amino acids and in the present investigation, amino acids of Securigera securidaca seeds have been evaluated. The ground seeds were extracted using petroleum ether, hot ethanol and ethanol 50%, respectively. ethanol 50% extract was chromatographed over cation exchanging resin and the resulting amino acid fraction was subjected to HPLC after OPA derivatization and the amino acids were identified by comparing to standards. The results evidenced the presence of 19 amino acids in the plant extract including alanine, arginine, asparagine, aspartic acid, citrulline, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, serine, threonine, tyrosine and valine. Considering the role of some amino acids in diabetes the above amino acids could be noted as hypoglycemic agents of the plant seeds but further studies are necessary.

  10. The synthesis of glutamic acid in the absence of enzymes: Implications for biogenesis

    Science.gov (United States)

    Morowitz, Harold; Peterson, Eta; Chang, Sherwood

    1995-01-01

    This paper reports on the non-enzymatic aqueous phase synthesis of amino acids from keto acids, ammonia and reducing agents. The facile synthesis of key metabolic intermediates, particularly in the glycolytic pathway, the citric acid cycle, and the first step of amino acid synthesis, lead to new ways of looking at the problem of biogenesis.

  11. Uranium extraction from phosphoric acid

    International Nuclear Information System (INIS)

    Lounis, A.

    1983-05-01

    A study has been carried out for the extraction of uranium from phosphoric acid produced in Algeria. First of all, the Algerian phosphoric acid produced in Algeria by SONATRACH has been characterised. This study helped us to synthesize a phosphoric acid that enabled us to pass from laboratory tests to pilot scale tests. We have then examined extraction and stripping parameters: diluent, DZEPHA/TOPO ratio and oxidising agent. The laboratory experiments enabled us to set the optimum condition for the choice of diluent, extractant concentration, ratio of the synergic mixture, oxidant concentration, redox potential. The equilibrium isotherms lead to the determination of the number of theoretical stages for the uranium extraction and stripping of uranium, then the extraction from phosphoric acid has been verified on a pilot scale (using a mixer-settler)

  12. 3,4,5-trihydroxybenzoic acid as chelating agent

    International Nuclear Information System (INIS)

    Agrawal, M.D.; Bhandari, C.S.; Dixit, M.K.; Sogani, N.C.

    1976-01-01

    Stability constants of praseodymium chelates of 3,4,5-trihydroxy sodium benzoate are determined by using Bjerrum-Calvin pH titration techniques at constant ionic strength 0.1M-sodium perchlorate and at 28+-0.1 0 C. Values calculated by different methods are in good agreement. The study reveals that during complexation only one proton of the ligand molecule is replaced by the metal and oxygen of adjacent phenolic group acts as a coordinating atom. IR and NMR spectral studies of the ligand reveal that one of the OH groups (in meta position to carboxylic group) remains free while two other phenolic groups are involved in intramolecular hydrogen bonding. One water molecule is found attached in crystalline gallic acid. (author)

  13. Dependence of radioprotective effect of chemical modifying agents on their intracellular concentrations

    International Nuclear Information System (INIS)

    Eidus, L.K.; Korystov, Y.N.; Kublik, L.N.; Vexler, A.M.

    1982-01-01

    Regularities of the radioprotective effect of chemical modifying agents cysteamine, caffeine benzoate, thioglycolic acid, and caffeine, all weak electrolytes, have been studied in cultured Chinese hamster cells. Efficiency of protection is shown to be dependent on pH and concentrations of the drug inside the cells and in the medium. Based on the theory of the dissociation of weak electrolytes and their distribution between the cells and the medium a strong correlation between the efficiency of modification of the radiation response and intracellular concentration of a modifying agent is shown. (author)

  14. Antimicrobial activity of poly(acrylic acid) block copolymers

    Energy Technology Data Exchange (ETDEWEB)

    Gratzl, Günther, E-mail: guenther.gratzl@jku.at [Johannes Kepler University Linz, Institute for Chemical Technology of Organic Materials, Altenberger Str. 69, 4040 Linz (Austria); Paulik, Christian [Johannes Kepler University Linz, Institute for Chemical Technology of Organic Materials, Altenberger Str. 69, 4040 Linz (Austria); Hild, Sabine [Johannes Kepler University Linz, Institute of Polymer Science, Altenberger Str. 69, 4040 Linz (Austria); Guggenbichler, Josef P.; Lackner, Maximilian [AMiSTec GmbH and Co. KG, Leitweg 13, 6345 Kössen, Tirol (Austria)

    2014-05-01

    The increasing number of antibiotic-resistant bacterial strains has developed into a major health problem. In particular, biofilms are the main reason for hospital-acquired infections and diseases. Once formed, biofilms are difficult to remove as they have specific defense mechanisms against antimicrobial agents. Antimicrobial surfaces must therefore kill or repel bacteria before they can settle to form a biofilm. In this study, we describe that poly(acrylic acid) (PAA) containing diblock copolymers can kill bacteria and prevent from biofilm formation. The PAA diblock copolymers with poly(styrene) and poly(methyl methacrylate) were synthesized via anionic polymerization of tert-butyl acrylate with styrene or methyl methacrylate and subsequent acid-catalyzed hydrolysis of the tert-butyl ester. The copolymers were characterized via nuclear magnetic resonance spectroscopy (NMR), size-exclusion chromatography (SEC), Fourier transform infrared spectroscopy (FTIR), elemental analysis, and acid–base titrations. Copolymer films with a variety of acrylic acid contents were produced by solvent casting, characterized by atomic force microscopy (AFM) and tested for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The antimicrobial activity of the acidic diblock copolymers increased with increasing acrylic acid content, independent of the copolymer-partner, the chain length and the nanostructure. - Highlights: • Acrylic acid diblock copolymers are antimicrobially active. • The antimicrobial activity depends on the acrylic acid content in the copolymer. • No salts, metals or other antimicrobial agents are needed.

  15. Antimicrobial activity of poly(acrylic acid) block copolymers

    International Nuclear Information System (INIS)

    Gratzl, Günther; Paulik, Christian; Hild, Sabine; Guggenbichler, Josef P.; Lackner, Maximilian

    2014-01-01

    The increasing number of antibiotic-resistant bacterial strains has developed into a major health problem. In particular, biofilms are the main reason for hospital-acquired infections and diseases. Once formed, biofilms are difficult to remove as they have specific defense mechanisms against antimicrobial agents. Antimicrobial surfaces must therefore kill or repel bacteria before they can settle to form a biofilm. In this study, we describe that poly(acrylic acid) (PAA) containing diblock copolymers can kill bacteria and prevent from biofilm formation. The PAA diblock copolymers with poly(styrene) and poly(methyl methacrylate) were synthesized via anionic polymerization of tert-butyl acrylate with styrene or methyl methacrylate and subsequent acid-catalyzed hydrolysis of the tert-butyl ester. The copolymers were characterized via nuclear magnetic resonance spectroscopy (NMR), size-exclusion chromatography (SEC), Fourier transform infrared spectroscopy (FTIR), elemental analysis, and acid–base titrations. Copolymer films with a variety of acrylic acid contents were produced by solvent casting, characterized by atomic force microscopy (AFM) and tested for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The antimicrobial activity of the acidic diblock copolymers increased with increasing acrylic acid content, independent of the copolymer-partner, the chain length and the nanostructure. - Highlights: • Acrylic acid diblock copolymers are antimicrobially active. • The antimicrobial activity depends on the acrylic acid content in the copolymer. • No salts, metals or other antimicrobial agents are needed

  16. Acid decomposition processing system for radioactive wastes

    International Nuclear Information System (INIS)

    Oomine, Toshimitsu.

    1984-01-01

    Purpose: To perform plutonium recovery at a low energy consumption irrespective of the plutonium density within the wastes. Method: In a decomposing and volume-reducing device for combustible or less combustible wastes containing transuranic elements using an acid, the wastes are in contact with nitric acid before feeding to a reactor. Then, the transuranic elements are transferred into the nitric acid, which is then in contact with ion exchange resins. After adsorbing the transuranic elements to the ion exchange resins, the nitric acid removed with the transuranic elements is caused to flow into a reaction vessel or heating vessel and used as a decomposing and oxidizing agent. (Seki, T.)

  17. Pilot trials with a fluorescent whitening agent of the bis(triazoly) stilbene-disulfonic acid type in golden orfes.

    Science.gov (United States)

    Hamburger, B; Maul, W; Patzschke, K; Theidel, H; Wegner, L A

    1975-01-01

    Golden orfes were examined for uptake, distribution, and elimination of radioactivity administered in the form of a 14C-labelled fluorescent whitening agent (FWA) of the bis(triazolyl)stilbenedisulfonic acid type. Results of these studies are given below. Pilot trials using FWA concentrations of 10 and 100 ppb and a population density of 1 fish per liter show that an equilibrium between uptake and elimination of the FWA develops in the animals within a period of one week; i.e., the incorporated traces of the FWA are not irreversibly bound. The radioactivity is mainly located in the gall bladder and in the intestinal contents, as well as in the liver, throat, and gills. The muscular system (filet) is virtually free from activity. Approximately 1-2% of the FWA amount administered per animal (corresponding to the concentration factors of 7-14) can be temporarily detected in the fish. Radioactivity is eliminated comparatively quickly. Two days following the transfer of the fish into water free from FWA a concentration factor as low as 1 is reached, i.e. from this time the FWA concentration in the animals decreases to less than 10 resp. 100 ppb.

  18. Inhibition of fatty acid synthesis in isolated adipocytes by 5-(tetradecyloxy)-2-furoic acid.

    Science.gov (United States)

    Halvorson, D L; McCune, S A

    1984-11-01

    The compound 5-(tetradecyloxy)-2-furoic acid (TOFA), a hypolipidemic agent, inhibits fatty acid synthesis, lactate and pyruvate accumulation and CO2 release in isolated rat adipocytes. TOFA stimulates the accumulation of citrate. ATP levels are not lowered by TOFA. In comparison with the natural fatty acid, oleate, TOFA exhibited a much greater inhibitory effect on lipogenesis. TOFyl-CoA formation within intact adipocytes was demonstrated. Although not inhibited by TOFA, acetyl-CoA carboxylase is inhibited by TOFyl-CoA. It is proposed that many of the metabolic effects of TOFA in isolated adipocytes can be explained by TOFyl-CoA inhibition of acetyl-CoA carboxylase. TOFA inhibits glycolysis as a secondary event with the primary event of inhibition of fatty acid synthesis causing an accumulation of citrate which is an inhibitor of phosphofructokinase.

  19. Nitric Acid Poisoning: Case Report

    International Nuclear Information System (INIS)

    Quintero Giraldo, Maria Paulina; Quiceno Calderon, William de Jesus; Melo Arango Catalina

    2011-01-01

    Nitric acid (HNO 3 ) is a corrosive fluid that, when in contact with reducing agents, generates nitrogen oxides that are responsible for inhalation poisoning. We present two cases of poisoning from nitric acid gas inhalation resulting from occupational exposure. Imaging findings were similar in both cases, consistent with adult respiratory distress syndrome (ARDS): bilaterally diffuse alveolar opacities on the chest X-ray and a cobblestone pattern on computed tomography (CT).one of the patients died while the other evolved satisfactorily after treatment with n-acetyl cysteine and mechanical ventilation. The diagnosis of nitric acid poisoning was made on the basis of the history of exposure and the way in which the radiological findings evolved.

  20. [Alkylating agents].

    Science.gov (United States)

    Pourquier, Philippe

    2011-11-01

    With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

  1. Metal complex-based templates and nanostructures for magnetic resonance/optical multimodal imaging agents

    NARCIS (Netherlands)

    Galindo Millan, Jealemy

    2012-01-01

    In this thesis, new approaches directed towards simple and functional imaging agents (IAs) for magnetic resonance (MR) and fluorescence multimodal imaging are proposed. In Chapter 3, hybrid silver nanostructures (hAgNSs), grown using a polyamino carboxylic acid scaffold, namely

  2. Procedure for the preparation of a radiodiagnostic agent for skeletal scintigraphy

    International Nuclear Information System (INIS)

    Budsky, F.; Kopecky, P.; Prokop, J.

    1997-01-01

    The procedure for the preparation of a radiodiagnostic agent based on an aminomethylphosphonic acid and 99m Tc is as follows: One mol of high-purity diethylenetriamine trihydrochloride, which is obtained by precipitating diethylenetriamine in methanol with azeotropic hydrochloric acid, and 5.3 mol of orthophosphoric acid are dissolved in 2 mol of azeotropic hydrochloric acid at 100-110 degC and reacted with a 34%-36% formaldehyde solution (5.6 mol) at the same temperature for a minimum of 60 min. The mixture is purified by repeated extraction with pentanol at 50 degC and evaporated to dryness. The residue is suspended in isopropanol and the suspension is evaporated to dryness again. The residue is boiled consecutively with dimethylformamide and with glacial acetic acid, dissolved in water, and precipitated with methanol to obtain diethylenetriamino-N,N,N',N',N''-pentakis(methylenephosphonic) acid (DTPMP). This product is filtered out, rinsed with methanol, and dried over sulfuric acid at 3 kPa for 3-5 days. The medical form is prepared by dissolving calcium carbonate in 0.1-1M aqueous DTPMP so that the two chemicals are in the molar ratio 1:1, and the solution is neutralized with sodium hydroxide so that the hydroxide-to-DTPMP molar ratio is 3:1. To the solution, freed from dissolved oxygen, a solution of tin dichloride in dilute hydrochloric acid is added so that the tin-to-DTPMP molar ratio is 1:10 to 2:10. Sodium hydroxide is added in order to exactly neutralize the hydrochloric acid, and the solution is subjected to sterile filtration and filled in vials. Each vial will contain 15-25 μmol DTPMP. The medical form is a lyophilisate of the monocalcium-trisodium salt of diethyleneamino-N,N,N',N',N''-pentakis(methylenephosphonic) salt and its complex with divalent tin. The radiodiagnostic agent is prepared by dissolving in the vial the eluate from a 99m Tc generator (0.25-5 ml) at activities of 250-2500 MBq. The Tc complex so obtained will be stable for a minimum

  3. The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo.

    Science.gov (United States)

    Susanto, Johana M; Colvin, Emily K; Pinese, Mark; Chang, David K; Pajic, Marina; Mawson, Amanda; Caldon, C Elizabeth; Musgrove, Elizabeth A; Henshall, Susan M; Sutherland, Robert L; Biankin, Andrew V; Scarlett, Christopher J

    2015-05-01

    Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera-peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls (DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.

  4. Synthesis, effect of capping agents, structural, optical and photoluminescence properties of ZnO nanoparticles

    International Nuclear Information System (INIS)

    Singh, A.K.; Viswanath, V.; Janu, V.C.

    2009-01-01

    Zinc oxide nanoparticles were synthesized using chemical method in alcohol base. During synthesis three capping agents, i.e. triethanolamine (TEA), oleic acid and thioglycerol, were used and the effect of concentrations was analyzed for their effectiveness in limiting the particle growth. Thermal stability of ZnO nanoparticles prepared using TEA, oleic acid and thioglycerol capping agents, was studied using thermogravimetric analyzer (TGA). ZnO nanoparticles capped with TEA showed maximum weight loss. X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used for structural and morphological characterization of ZnO nanoparticles. Particle size was evaluated using effective mass approximation method from UV-vis spectroscopy and Scherrer's formula from XRD patterns. XRD analysis revealed single crystal ZnO nanoparticles of size 12-20 nm in case of TEA capping. TEA, oleic acid and thioglycerol capped synthesized ZnO nanoparticles were investigated at room temperature photoluminescence for three excitation wavelengths i.e. 304, 322 and 325 nm, showing strong peaks at about 471 nm when excited at 322 and 325 nm whereas strong peak was observed at 411 for 304 nm excitation.

  5. N-cinnamoylated aminoquinolines as promising antileishmanial agents.

    Science.gov (United States)

    Vale-Costa, S; Costa-Gouveia, J; Pérez, B; Silva, T; Teixeira, C; Gomes, P; Gomes, M S

    2013-10-01

    A series of cinnamic acid conjugates of primaquine and chloroquine were evaluated for their in vitro antileishmanial activities. Although primaquine derivatives had modest activity, chloroquine conjugates exhibited potent activity against both promastigotes (50% inhibitory concentration [IC50] = 2.6 to 21.8 μM) and intramacrophagic amastigotes (IC50 = 1.2 to 9.3 μM) of Leishmania infantum. Both the high activity of these chloroquine analogues and their mild-to-low toxicity toward host cells make them promising leads for the discovery of new antileishmanial agents.

  6. Safety Assessment of Amino Acid Alkyl Amides as Used in Cosmetics.

    Science.gov (United States)

    Burnett, Christina L; 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

    The Cosmetic Ingredient Review Expert Panel (Panel) reviewed the product use, formulation, and safety data of 115 amino acid alkyl amides, which function as skin and hair conditioning agents and as surfactants-cleansing agents in personal care products. Safety test data on dermal irritation and sensitization for the ingredients with the highest use concentrations, lauroyl lysine and sodium lauroyl glutamate, were reviewed and determined to adequately support the safe use of the ingredients in this report. The Panel concluded that amino acid alkyl amides are safe in the present practices of use and concentration in cosmetics, when formulated to be nonirritating.

  7. Facile synthesis of octahedral Pt-Pd nanoparticles stabilized by silsesquioxane for the electrooxidation of formic acid

    International Nuclear Information System (INIS)

    Li, Yusong; Hao, Furui; Wang, Yihong; Zhang, Yihong; Ge, Cunwang; Lu, Tianhong

    2014-01-01

    Graphical abstract: The octahedral Pt-Pd alloy nanoparticles (octahedral Pt-Pd NPs) with dominant {111} facets were successfully synthesized through a facile route in the presence of octa(3-aminopropyl) silsesquioxane as the capping agent and complexing agent, methanol as the reductant and solvent. The octahedral Pt-Pd NPs display the significantly enhanced electrocatalytic activity, increased CO tolerance and favourable stability for the electrooxidation of formic acid. - Highlights: • Octa Pt-Pd nanoparticles were synthesized with silsesquioxane as capping agent. • Octa Pt-Pd nanoparticles display uniform morphology and favorable dispersibility. • Octa Pt-Pd nanoparticles have high catalytic activity for formic acid by direct process. - Abstract: The octahedral Pt-Pd alloy nanoparticles (octahedral Pt-Pd NPs) with dominant {111} facets were successfully synthesized through a facile route in the presence of octa(3-aminopropyl) silsesquioxane as the capping agent and complexing agent, methanol as the reductant and solvent. Their morphology, composition and structure were charactered by transmission electron microscopy (TEM), energy dispersive spectrum (EDS) and X-ray diffraction (XRD). The electrocatalytic activity, CO tolerance and stability of the octahedral Pt-Pd NPs for the electrooxidation of formic acid were investigated by cyclic voltammetry, CO stripping voltammetry and chronoamperometry, respectively. Compared with the Pt nanoparticles and commercial Pt black, the octahedral Pt-Pd NPs display a significantly enhanced electrocatalytic activity, increased CO tolerance and favourable stability for the electrooxidation of formic acid. Therefore, the octahedral Pt-Pd NPs might be an alternative candidate for the anode catalyst for the electrooxidation of formic acid in future

  8. On the Use of Molecular Weight Cutoff Cassettes to Measure Dynamic Relaxivity of Novel Gadolinium Contrast Agents: Example Using Hyaluronic Acid Polymer Complexes in Phosphate-Buffered Saline

    Directory of Open Access Journals (Sweden)

    Nima Kasraie

    2011-01-01

    Full Text Available The aims of this study were to determine whether standard extracellular contrast agents of Gd(III ions in combination with a polymeric entity susceptible to hydrolytic degradation over a finite period of time, such as Hyaluronic Acid (HA, have sufficient vascular residence time to obtain comparable vascular imaging to current conventional compounds and to obtain sufficient data to show proof of concept that HA with Gd-DTPA ligands could be useful as vascular imaging agents. We assessed the dynamic relaxivity of the HA bound DTPA compounds using a custom-made phantom, as well as relaxation rates at 10.72 MHz with concentrations ranging between 0.09 and 7.96 mM in phosphate-buffered saline. Linear dependences of static longitudinal relaxation rate (R1 on concentration were found for most measured samples, and the HA samples continued to produce high signal strength after 24 hours after injection into a dialysis cassette at 3T, showing superior dynamic relaxivity values compared to conventional contrast media such as Gd-DTPA-BMA.

  9. Determination of peracetic acid and hydrogen peroxide in the mixture

    OpenAIRE

    Bodiroga Milanka; Ognjanović Jasminka

    2002-01-01

    Iodometric and permanganometric titrations were used for determination of peracetic acid and hydrogen peroxide (H2O2) in the mixture. Two procedures were described and compared. Titrations could be done in only one vessel, in the same reaction mixture, when iodometric titration of peracetic acid was continued after the permanganometric titration of H2O2, (procedure A). Peracetic acid and H2O2, as oxidizing agents, reacted with potassium iodide in an acid medium, evolving iodine. This reaction...

  10. Synthesis, characterization, bioactivity and potential application of phenolic acid grafted chitosan: A review.

    Science.gov (United States)

    Liu, Jun; Pu, Huimin; Liu, Shuang; Kan, Juan; Jin, Changhai

    2017-10-15

    In recent years, increasing attention has been paid to the grafting of phenolic acid onto chitosan in order to enhance the bioactivity and widen the application of chitosan. Here, we present a comprehensive overview on the recent advances of phenolic acid grafted chitosan (phenolic acid-g-chitosan) in many aspects, including the synthetic method, structural characterization, biological activity, physicochemical property and potential application. In general, four kinds of techniques including carbodiimide based coupling, enzyme catalyzed grafting, free radical mediated grafting and electrochemical methods are frequently used for the synthesis of phenolic acid-g-chitosan. The structural characterization of phenolic acid-g-chitosan can be determined by several instrumental methods. The physicochemical properties of chitosan are greatly altered after grafting. As compared with chitosan, phenolic acid-g-chitosan exhibits enhanced antioxidant, antimicrobial, antitumor, anti-allergic, anti-inflammatory, anti-diabetic and acetylcholinesterase inhibitory activities. Notably, phenolic acid-g-chitosan shows potential applications in many fields as coating agent, packing material, encapsulation agent and bioadsorbent. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Tranexamic Acid Failed to Reverse the Anticoagulant Effect and Bleeding by an Oral Direct Factor Xa Inhibitor Edoxaban.

    Science.gov (United States)

    Honda, Yuko; Furugohri, Taketoshi; Morishima, Yoshiyuki

    2018-01-01

    Agents to reverse the anticoagulant effect of edoxaban, an oral direct factor Xa inhibitor, would be desirable in emergency situations. The aim of this study is to determine the effect of tranexamic acid, an antifibrinolytic agent, on the anticoagulant activity and bleeding by edoxaban in rats. A supratherapeutic dose of edoxaban (3 mg/kg) was intravenously administered to rats. Three minutes after dosing, tranexamic acid (100 mg/kg) was given intravenously. Bleeding was induced by making an incision with a blade on the planta 8 min after edoxaban injection and bleeding time was measured. Prothrombin time (PT) and clot lysis were examined. A supratherapeutic dose of edoxaban significantly prolonged PT and bleeding time. Tranexamic acid did not affect PT or bleeding time prolonged by edoxaban, although tranexamic acid significantly inhibited clot lysis in rat plasma. An antifibrinolytic agent tranexamic acid failed to reverse the anticoagulant effect and bleeding by edoxaban in rats. © 2017 S. Karger AG, Basel.

  12. Potential of radiosensitizing agents in cancer chemo-radiotherapy

    Directory of Open Access Journals (Sweden)

    Girdhani S

    2005-01-01

    Full Text Available Potential of herbs and other plant-based formulations have been increasingly recognized in prevention and treatment of human diseases including cancer. There exist enormous prospect for screening and evaluation of herbal/plant products for developing effective radiosensitization and radioprotection relevant to nuclear research program. Investigations in our laboratory have focused on the mechanism of activity of variety of anticancer and antioxidant agents, namely, Eugenol, (EU, Ellagic acid (EA, Triphala (TPL, Tocopherol Succinate (TOS and Arachidonic acid on normal and cancer cells with view to design effective protocols in practical radioprotection and cancer radiotherapy. This paper is mainly focused on studies on cytotoxic effects on cancer cell lines. Results have shown that these agents produced radiosensitizing action involving oxidative damage, membrane alteration and damage to nucleic acid in various human cell lines. Studies were performed employing fluorescence probes and electron spin resonance methods and gel electrophoresis protocols. It has been found that cytotoxic effect was induced by initiating membrane oxidative damage and by triggering intracellular generation of reactive oxygen species (ROS by gamma radiation in combination with phytochemicals like TPL, EA and TOS in tumor cell line Ehrlich Ascites (EAC, Human cervical (HeLa and breast (MCF-7 cells. Membrane damage and ROS generation was measured by DPH and DCF-FDA fluorescent probes respectively after exposure to low to moderate doses of gamma radiation. This talk will present the cytotoxic effects of phytochemicals in combination with ionizing radiation. It is emphasized that modulation of membrane peroxidative damage and intra cellular ROS may help achieve efficient killing of cancer cells which may provide a new approach to developing effective treatment of cancer.

  13. [Research of preparation craft of Danshen phenolic acid fast release unit in multi-drug delivery system of Tongmai micro-pellets].

    Science.gov (United States)

    Chen, Bin; Xiao, Wei; Jia, Xiao-Bin; Huang, Yang

    2012-07-01

    To prepare Danshen phenolic acid fast release micro-pellets and study its preparation craft. The factors which could impact yield, extrude shaping, dissolution of Danshen phenolic acid micro-pellets such as wetting agent, drug loading dose, adjuvant, lactose dose, disintegrant, CMS-Na dose and wetting agent dose was investigated. The optimum preparation craft of Danshen phenolic acid fast release micro-pellets was screened out by orhogonal design. Formula of Danshen phenolic acid fast release micro-pellets was calculated as volume dose 50 g. The formula was as follows: principal agent 22.5 g, lactose 5 g, CMS-Na 2 g, MCC 20.5 g, 27 mL 30% ethanol as wetting agent. Extrusion-spheronization was applied. The optimum conditions were screened out as follows: extrusion frequency (25 Hz), spheronization machine frequency (50 Hz), spheronization time (4 min). The process was scientific and rational. The preparation is stable settles basis for multi-drug delivery system of Tongmai micro-pellets.

  14. Incorporating BDI Agents into Human-Agent Decision Making Research

    Science.gov (United States)

    Kamphorst, Bart; van Wissen, Arlette; Dignum, Virginia

    Artificial agents, people, institutes and societies all have the ability to make decisions. Decision making as a research area therefore involves a broad spectrum of sciences, ranging from Artificial Intelligence to economics to psychology. The Colored Trails (CT) framework is designed to aid researchers in all fields in examining decision making processes. It is developed both to study interaction between multiple actors (humans or software agents) in a dynamic environment, and to study and model the decision making of these actors. However, agents in the current implementation of CT lack the explanatory power to help understand the reasoning processes involved in decision making. The BDI paradigm that has been proposed in the agent research area to describe rational agents, enables the specification of agents that reason in abstract concepts such as beliefs, goals, plans and events. In this paper, we present CTAPL: an extension to CT that allows BDI software agents that are written in the practical agent programming language 2APL to reason about and interact with a CT environment.

  15. Inositol hexa-phosphate: a potential chelating agent for uranium

    International Nuclear Information System (INIS)

    Cebrian, D.; Tapia, A.; Real, A.; Morcillo, M.A.

    2007-01-01

    Chelation therapy is an optimal method to reduce the radionuclide-related risks. In the case of uranium incorporation, the treatment of choice is so far i.v infusion of a 1.4% sodium bicarbonate solution, but the efficacy has been proved to be not very high. In this study, we examine the efficacy of some substances: bicarbonate, citrate, diethylenetriamine pentaacetic acid (DTPA), ethidronate (EHBP) and inositol hexa-phosphate (phytic acid) to chelate uranium using a test developed by Braun et al. Different concentrations of phytic acid, an abundant component of plant seeds that is widely distributed in animal cells and tissues in substantial levels, were tested and compared to the same concentrations of sodium citrate, bicarbonate, EHBP and DTPA. The results showed a strong affinity of inositol hexa-phosphate for uranium, suggesting that it could be an effective chelating agent for uranium in vivo. (authors)

  16. Extraction of Uranium in The Mixtures of Nitric and Sulfuric Acids With Neutral and Basic Ligands in Kerosene

    International Nuclear Information System (INIS)

    Nampira, Y; Rahayu Imam, S; Djoyosubroto, H

    1998-01-01

    The tendency of uranium ion in the mixture of nitric and sulfuric acid's medium is to from uranyl sulphate complex. The compound of uranyl sulphate is containing into the heteropoly compound that has acid property. Regarding to the mentioned property, the U extraction process was carried out using a basic or neutral complexing agent containing a ligand that formed the soluble uranium complex in the organic solvent (kerosene).The use of basic complexing agent such as n,tri-octyl amine is more suitable than that of tri butyl phosphate as a neutral agent. The maximum distribution coefficient of uranium will be reached if the maximum concentration of nitric acid and sulphuric acid can be maintained at 0.3 M and 1.5 M respectively in the organic solvent medium consisted n,tri-octyl amine of 30% volume fraction

  17. Chemical warfare agents.

    Science.gov (United States)

    Kuca, Kamil; Pohanka, Miroslav

    2010-01-01

    Chemical warfare agents are compounds of different chemical structures. Simple molecules such as chlorine as well as complex structures such as ricin belong to this group. Nerve agents, vesicants, incapacitating agents, blood agents, lung-damaging agents, riot-control agents and several toxins are among chemical warfare agents. Although the use of these compounds is strictly prohibited, the possible misuse by terrorist groups is a reality nowadays. Owing to this fact, knowledge of the basic properties of these substances is of a high importance. This chapter briefly introduces the separate groups of chemical warfare agents together with their members and the potential therapy that should be applied in case someone is intoxicated by these agents.

  18. The role indigenous bacterial isolates for bioremediation agent in the uranium contaminated aquatic environment

    International Nuclear Information System (INIS)

    Mochd Yazid

    2014-01-01

    A Research on the role of indigenous bacterial isolates for bio-remediation agent of the uranium contaminated in the aquatic environment has been conducted. The objective of the research is to study the role of Pseudomonas sp and Bacillus sp. have been isolated from low level uranium waste for bioremediation agent in their environment, such as the determination of efficiency of the uranium binding compared by the non indigenous bacterial, location of these binding and the influences of added acethyl acid stimulant. The uranium reduction studied was measured by weighting bacterial biomass and uranium concentration was measured by spectrophotometer. The acethyl acid stimulant addition has been done with the variation of concentration and volume. The efficiency of the uranium reduction by indigenous bacterial isolate such as Pseudomonas sp were 84.99 % and Bacillus sp were 52.70 %, so the reduction efficiency by non indigenous bacterial such as Pseudomonas aerogenes were 78.47 % and Bacillus subtilis were 45.22 % for 54 hours incubation time. The result of this research can be concluded that Pseudomonas sp and Bacillus sp. Indigenous bacterial have been isolates from the liquid uranium waste can contributed in bioremediation agent for uranium radionuclide in the environment for 60 ppm concentration with reduction efficiency 52.70 %-84.99 %, that is higher non indigenous bacterial for 54 hours incubation time, the stimulant addition of acethyl acid, the efficiency can be increased up to 99.8 %. (author)

  19. Podophyllotoxin: a novel potential natural anticancer agent

    Directory of Open Access Journals (Sweden)

    Hamidreza Ardalani

    2017-06-01

    Full Text Available Objective: The aim of the present review is to give an overview about the role, biosynthesis, and characteristics of Podophyllotoxin (PTOX as a potential antitumor agent with particular emphasis on key biosynthesis processes, function of related enzymes and characterization of genes encoding the enzymes. Materials and Methods: Google scholar, PubMed and Scopus were searched for literatures which have studied identification, characterization, fermentation and therapeutic effects of PTOX and published in English language until end of 2016. Results: PTOX is an important plant-derived natural product, has derivatives such as etoposide and teniposide, which have been used as therapies for cancers and venereal wart. PTOX structure is closely related to the aryltetralin lactone lignans that have antineoplastic and antiviral activities. Podophyllum emodi Wall. (syn. P. hexandrum and Podophyllum peltatum L. (Berberidaceae are the major sources of PTOX. It has been shown that ferulic acid and methylenedioxy substituted cinnamic acid are the enzymes involved in PTOX synthesis. PTOX prevents cell growth via polymerization of tubulin, leading to cell cycle arrest and suppression of the formation of the mitotic-spindles microtubules.   Conclusion: Several investigations have been performed in biosynthesis of PTOX such as cultivation of these plants, though they were unsuccessful. Thus, it is important to find alternative sources to satisfy the pharmaceutical demand for PTOX. Moreover, further preclinical studies are warranted to explore the molecular mechanisms of these agents in treatment of cancer and their possible potential to overcome chemoresistance of tumor cells.

  20. Podophyllotoxin: a novel potential natural anticancer agent

    Science.gov (United States)

    Ardalani, Hamidreza; Avan, Amir; Ghayour-Mobarhan, Majid

    2017-01-01

    Objective: The aim of the present review is to give an overview about the role, biosynthesis, and characteristics of Podophyllotoxin (PTOX) as a potential antitumor agent with particular emphasis on key biosynthesis processes, function of related enzymes and characterization of genes encoding the enzymes. Materials and Methods: Google scholar, PubMed and Scopus were searched for literatures which have studied identification, characterization, fermentation and therapeutic effects of PTOX and published in English language until end of 2016. Results: PTOX is an important plant-derived natural product, has derivatives such as etoposide and teniposide, which have been used as therapies for cancers and venereal wart. PTOX structure is closely related to the aryltetralin lactone lignans that have antineoplastic and antiviral activities. Podophyllum emodi Wall. (syn. P. hexandrum) and Podophyllum peltatum L. (Berberidaceae) are the major sources of PTOX. It has been shown that ferulic acid and methylenedioxy substituted cinnamic acid are the enzymes involved in PTOX synthesis. PTOX prevents cell growth via polymerization of tubulin, leading to cell cycle arrest and suppression of the formation of the mitotic-spindles microtubules. Conclusion: Several investigations have been performed in biosynthesis of PTOX such as cultivation of these plants, though they were unsuccessful. Thus, it is important to find alternative sources to satisfy the pharmaceutical demand for PTOX. Moreover, further preclinical studies are warranted to explore the molecular mechanisms of these agents in treatment of cancer and their possible potential to overcome chemoresistance of tumor cells. PMID:28884079

  1. A microneedle biosensor for minimally-invasive transdermal detection of nerve agents.

    Science.gov (United States)

    Mishra, Rupesh K; Vinu Mohan, A M; Soto, Fernando; Chrostowski, Robert; Wang, Joseph

    2017-03-13

    A microneedle electrochemical biosensor for the minimally invasive detection of organophosphate (OP) chemical agents is described. The new sensor relies on the coupling of the effective biocatalytic action of organophosphorus hydrolase (OPH) with a hollow-microneedle modified carbon-paste array electrode transducer, and involves rapid square-wave voltammetric (SWV) measurements of the p-nitrophenol product of the OPH enzymatic reaction in the presence of the OP substrate. The scanning-potential SWV transduction mode offers an additional dimension of selectivity compared to common fixed-potential OPH-amperometric biosensors. The microneedle device offers a highly linear response for methyl paraoxon (MPOx) over the range of 20-180 μM, high selectivity in the presence of excess co-existing ascorbic acid and uric acid and a high stability sensor upon exposure to the interstitial fluid (ISF). The OPH microneedle sensor was successfully tested ex vivo using mice skin samples exposed to MPOx, demonstrating its promise for minimally-invasive monitoring of OP agents and pesticides and as a wearable sensor for detecting toxic compounds, in general.

  2. Organic complexing agents in low and medium level radioactive waste

    International Nuclear Information System (INIS)

    Allard, B.; Persson, G.

    1985-11-01

    Low and medium level radioactive wastes will contain various organic agents, such as ion exchange resins (mainly in the operational wastes), plastics and cellulose (mainly in the reprocessing wastes and in the decommissioning wastes) and bitumen (mainly in the reprocessing wastes). The degradation of these organics will lead to the formation of complexing agents that possibly could affect the release of radionuclides from an underground repository and the subsequent transport of these nuclides. The solution chemistry of the actinides may be totally dominated by the presence of such organic degradation products within the repository. However, hydrolysis and formation of carbonates (and possibly humates) will most likely dominate solubility and speciation outside the immediate vicinity of the repository. The minor quantities of strong complexing agents (in the reprocessing waste), notably aminopolycarboxylic acids (EDTA, DTPA) and possibly organic phosphates (DBP) could significantly affect speciation and sorption behaviour of primarily the trivalent actinides even outside the repository. (author)

  3. Logics for Intelligent Agents and Multi-Agent Systems

    NARCIS (Netherlands)

    Meyer, John-Jules Charles

    2014-01-01

    This chapter presents the history of the application of logic in a quite popular paradigm in contemporary computer science and artificial intelligence, viz. the area of intelligent agents and multi-agent systems. In particular we discuss the logics that have been used to specify single agents, the

  4. Preparation of cathode materials for Li-ion cells by acid dissolution

    International Nuclear Information System (INIS)

    Oh, Si Hyoung; Jeong, Woon Tae; Cho, Won Il; Cho, Byung Won; Woo, Kyoungja

    2005-01-01

    New synthesis route called acid dissolution method, preparing the high-performance cathode materials for the lithium-ion cells, was successfully developed. In this method, insoluble starting materials such as metal carbonates or metal hydroxides are dissolved in strong organic acidic solution which contains a chelating agent. And then, the solvent of the solution containing starting materials is eliminated to obtain the xerogel of the initial solution whose chemical form is expressed as Li[MA 3 ], where M is a transition metal atom and A is the anion of the organic acid. The xerogel is then calcined at the high temperature to obtain polycrystalline cathode materials. In this work, the applicability of this method was demonstrated synthesizing a polycrystalline single-phase LiCoO 2 using lithium carbonate, cobalt hydroxide as the insoluble starting materials and the acrylic acid as a chelating agent. The synthesized powders calcined at 800 deg. C showed a good electrochemical performance in the half-cell test

  5. Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents.

    Directory of Open Access Journals (Sweden)

    Anna Gliszczyńska

    Full Text Available The synthesis of novel phosphatidylcholines with geranic and citronellic acids in sn-1 and sn-2 positions is described. The structured phospholipids were obtained in high yields (59-87% and evaluated in vitro for their cytotoxic activity against several cancer cell lines of different origin: MV4-11, A-549, MCF-7, LOVO, LOVO/DX, HepG2 and also towards non-cancer cell line BALB/3T3 (normal mice fibroblasts. The phosphatidylcholines modified with monoterpene acid showed a significantly higher antiproliferative activity than free monoterpene acids. The highest activity was observed for the terpene-phospholipids containing the isoprenoid acids in sn-1 position of phosphatidylcholine and palmitic acid in sn-2.

  6. Development of organic MRI contrast agents

    International Nuclear Information System (INIS)

    Hayashi, Hiroyuki; Sato, Yuichiro; Karasawa, Satoru; Koga, Noboru

    2008-01-01

    Described are trends of the development in the title since those agents with target properties are awaited for specific organ and regional MRI. The contrast agents alter the relaxation time of water proton to yield the enhanced contrast between organs and tissues with different water volumes. Nowadays Gd-complexes and nano-particle of superparamagnetic iron oxide (Fe(III)) are widely used for enhancing in clinic. Among organic compounds with paramagnetic spin, those possessing nitroxide radical like TEMPO- and PROXYL-radicals have been subject to development by their derivatization. High spin molecules conceivably affect the relaxivity, which, however, is found smaller per spin of synthesized triplet complexes than doublet ones. This has lead to basic approach for molecules restricting water movement due to their hydrogen bond like DNA as a model, for introducing many radicals in high molecular weight compounds, and their polymer, as one of which authors have developed a derivative of hyperbranched polymer (HPS)-TEMPO having the similar relaxivity to gadolinium-diethylenetiamine pentaacetid acid (Gd-DTPA) (R.T.)

  7. Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging.

    Science.gov (United States)

    Mouffouk, Fouzi; Simão, Teresa; Dornelles, Daniel F; Lopes, André D; Sau, Pablo; Martins, Jorge; Abu-Salah, Khalid M; Alrokayan, Salman A; Rosa da Costa, Ana M; dos Santos, Nuno R

    2015-01-01

    Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35-40 nm) reveals their potential use for early cancer detection by MRI.

  8. Synthesis of microcapsules containing different extractant agents.

    Science.gov (United States)

    Alcázar, Ángela; Carmona, Manuel; Borreguero, Ana M; de Lucas, Antonio; Rodríguez, Juan F

    2015-01-01

    Mercury is one of the most toxic pollutants, with high capacity of accumulation in living organism, causing important human health problems. Therefore, the mercury removal from water is an important research goal. In a previous work, an extractant agent [di(2-ethylhexyl)phosphoric acid] was microencapsulated in poly(styrene-co-divinylbenzene) by means of suspension polymerisation using toluene as diluent. In this study, this recipe has been modified changing the toluene by heptane and extended to four additional extractants (trioctylamine, trioctylmethylammonium chloride [TOMAC], tributyl phosphate and trioctylphosphine oxide). The polluting potential of the waste liquid from the process was measured by total organic carbon and chemical oxygen demand analyses. The morphology, particle size and distribution were studied by scanning electron microscopy and low angle laser light scattering. The amount of extractant agent into the microcapsules and the microencapsulation efficiency were determined by thermogravimetric analysis and the mercury removal capacity by equilibrium studies. Microcapsules containing TOMAC demonstrated to be the best material for the mercury removal and retention.

  9. Transglycosylation of gallic acid by using Leuconostoc glucansucrase and its characterization as a functional cosmetic agent.

    Science.gov (United States)

    Nam, Seung-Hee; Park, Jeongjin; Jun, Woojin; Kim, Doman; Ko, Jin-A; Abd El-Aty, A M; Choi, Jin Young; Kim, Do-Ik; Yang, Kwang-Yeol

    2017-12-22

    Gallic acid glycoside was enzymatically synthesized by using dextransucrase and sucrose from gallic acid. After purification by butanol partitioning and preparative HPLC, gallic acid glucoside was detected at m/z 355 (C 13 , H 16 , O 10 , Na) + by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The yield of gallic acid glucoside was found to be 35.7% (114 mM) by response surface methodology using a reaction mixture of 319 mM gallic acid, 355 mM sucrose, and 930 mU/mL dextransucrase. The gallic acid glucoside obtained showed 31% higher anti-lipid peroxidation and stronger inhibition (Ki = 1.23 mM) against tyrosinase than that shown by gallic acid (Ki = 1.98 mM). In UVB-irradiated human fibroblast cells, gallic acid glucoside lowered matrix metalloproteinase-1 levels and increased the collagen content, which was indicative of a stronger anti-aging effect than that of gallic acid or arbutin. These results indicated that gallic acid glucoside is likely a superior cosmetic ingredient with skin-whitening and anti-aging functions.

  10. Withania somnifera attenuates acid production, acid tolerance and extra-cellular polysaccharide formation of Streptococcus mutans biofilms.

    Science.gov (United States)

    Pandit, Santosh; Song, Kwang-Yeob; Jeon, Jae-Gyu

    2014-01-01

    Withania somnifera (Ashwagandha) is a plant of the Solanaceae family. It has been widely used as a remedy for a variety of ailments in India and Nepal. The plant has also been used as a controlling agent for dental diseases. The aim of the present study was to evaluate the activity of the methanol extract of W. somnifera against the physiological ability of cariogenic biofilms and to identify the components of the extract. To determine the activity of the extract, assays for sucrose-dependent bacterial adherence, glycolytic acid production, acid tolerance, and extracellular polysaccharide formation were performed using Streptococcus mutans biofilms. The viability change of S. mutans biofilms cells was also determined. A phytochemical analysis of the extract was performed using TLC and LC/MS/MS. The extract showed inhibitory effects on sucrose-dependent bacterial adherence (≥ 100 μg/ml), glycolytic acid production (≥ 300 μg/ml), acid tolerance (≥ 300 μg/ml), and extracellular polysaccharide formation (≥ 300 μg/ml) of S. mutans biofilms. However, the extract did not alter the viability of S. mutans biofilms cells in all concentrations tested. Based on the phytochemical analysis, the activity of the extract may be related to the presence of alkaloids, anthrones, coumarines, anthraquinones, terpenoids, flavonoids, and steroid lactones (withanolide A, withaferin A, withanolide B, withanoside IV, and 12-deoxy withastramonolide). These data indicate that W. somnifera may be a potential agent for restraining the physiological ability of cariogenic biofilms.

  11. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

    Directory of Open Access Journals (Sweden)

    Donghee Park

    Full Text Available Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with

  12. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

    Science.gov (United States)

    Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

    2016-01-01

    Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the

  13. Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

    International Nuclear Information System (INIS)

    Lauffer, R.B.; Greif, W.L.; Stark, D.D.; Vincent, A.C.; Saini, S.; Wedeen, V.J.; Brady, T.J.

    1988-01-01

    A paramagnetic relaxation agent targeted to functioning hepatocytes of the liver and excreted into the bile would be useful in the enhancement of normal liver and biliary anatomy in MR imaging. We sought to demonstrate the feasibility of this approach using the prototype hepatobiliary MR contrast agent, iron(III) ethylenebis-(2-hydroxyphenylglycine) (Fe(EHPG) - ). The biodistribution, relaxation enhancement, and imaging characteristics of Fe(EHPG) - were compared to those of the non-specific iron chelate iron(III) diethylenetriaminepentaacetic acid (Fe(DTPA) 2- ), which has a comparable effect on water proton relaxation times. (author)

  14. New syntheses of No-carrier-added 123I-labeled agents via organoborane chemistry

    International Nuclear Information System (INIS)

    Kabalka, G.W.

    1985-01-01

    No-carrier-added 123 I-labeled agents are readily prepared via the reaction of organoboranes with sodium iodide- 123 I in the presence of mild oxidizing agents. The reactions are rapid and regiospecific, and they produce excellent yields of the labeled products. The organoboranes are readily prepared from alkenes and alkynes via the hydroboration reaction. A wide variety of functional groups are tolerated by the hydroboration-iodination sequence. The sequence has been utilized to prepare 123 I-labeled steroids and fatty acids, as well as a number of labeled esters, and aromatic derivatives

  15. Biological Agents

    Science.gov (United States)

    ... E-Tools Safety and Health Topics / Biological Agents Biological Agents This page requires that javascript be enabled ... 202) 693-2300 if additional assistance is required. Biological Agents Menu Overview In Focus: Ebola Frederick A. ...

  16. Synthesis and evaluation of new protecting agents against ionizing radiations

    International Nuclear Information System (INIS)

    Nadal, B.

    2009-10-01

    This thesis is devoted to the synthesis of new pulvinic acid derivatives and the evaluation of their antioxidant and radioprotective properties. This study has been conducted with the aim to develop new protecting agents against ionizing radiations. A new access to pulvinic acid derivatives was developed starting from L-dimethyl tartrate. It is based on a Dieckmann cyclization a dehydration and a Suzuki-Miyaura coupling. It allows a short effective preparation of various pulvinic acid derivatives: tetronic acid derivatives, mono-substituted pulvinic acid derivatives and methyl pulvinates. A modified method has been used to prepare pulvinones. This strategy gave access in four steps to the desired pulvinones. The rapidity of this method is provided by a tandem process, carried out in the final step, involving a Dieckmann cyclization and a β-elimination. A synthesis of 3-aryltetramic acids has also been developed in order to prepare nitrogen derivatives of pulvinic acid. The antioxidant activity of the prepared compounds was then evaluated using various tests: DPPH, ABTS, protection of thymidine and DNA study of lipid peroxidation. These evaluations allowed to define interesting structure-activity relationships of pulvinic derivatives. They have shown that several derivatives have very good antioxidant activities. Finally, radioprotective tests on TK6 cells and mice have have been performed on selected compounds. (author)

  17. Evaluation of selected neutralizing agents for the treatment of uranium tailings leachates. Laboratory progress report

    International Nuclear Information System (INIS)

    Sherwood, D.R.; Serne, R.J.

    1983-02-01

    Laboratory experiments were conducted to evaluate the performance of selected neutralizing agents for the treatment of uranium tailings solutions. Highly acidic tailings solutions (pH 3 ) reagent grade; Calcium hydroxide [Ca(OH) 2 ] reagent grade; Magnesium oxide (MgO) reagent grade; Sodium carbonate (Na 2 CO 3 ) reagent grade; and Sodium hydroxide (NaOH) reagent grade. Evaluation of the effectiveness for the treatment of uranium tailings solutions for the selected neutralizing agents under controlled laboratory conditions was based on three criteria. The criteria are: (1) treated effluent water quality, (2) neutralized sludge handling and hydraulic properties, and (3) reagent costs and acid neutralizing efficiency. On the basis of these limited laboratory results calcium hydroxide or its dehydrated form CaO (lime) appears to be the most effective option for treatment of uranium tailings solutions

  18. Topical undecylenic acid in tinea pedis: a new look.

    Science.gov (United States)

    Smith, E B; Powell, R P; Graham, J L; Ulrich, J A

    1977-01-01

    One hundred and four patients with mycologically confirmed tinea pedis took part in a controlled clinical trial to determine the efficacy of undecylenic acid powder preparations in the treatment of their fungal infections. Clinical and mycological cures were obtained in 53% of those subjects treated with undecylenic acid powders as compared with 7% of those treated with the talc vehicle or left untreated. Undecylenic acid in a powder vehicle appears to be a safe and effective agent in the treatment of tinea pedis.

  19. Biological evaluation of 99mTC cis-Pt iminoacetic acid complexes as tumour imaging agents

    International Nuclear Information System (INIS)

    Awaluddin, A.; Jacobs, J.J.; Bourne, D.W.; Maddalena, D.J.; Wilson, J.G.; Boyd, D.W.

    1987-01-01

    The biodistributions of three new 99m Tc labelled cis-platinum bifunctional tumour imaging agents were examined in mice bearing a certain type of sarcoma between 15 minutes and 24 hours post injection. The three complexes were excreted primarily via the renal pathway into the urine but at quite different rates. All complexes had some affinity for the tumour, but complexes III had the greatest, with tumour to blood and tumour to muscle rates at 24 hours in excess of 10:1 and 18:1. Biodistribution results were calculated using Tiscon Program. Suggesting that the three complexes may be useful as tumour imaging agents. (M.E.L.) [es

  20. Current and emerging treatment options in the management of lupus

    Science.gov (United States)

    Jordan, Natasha; D’Cruz, David

    2016-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease with variable clinical manifestations. While the clearest guidelines for the treatment of SLE exist in the context of lupus nephritis, patients with other lupus manifestations such as neuropsychiatric, hematologic, musculoskeletal, and severe cutaneous lupus frequently require immunosuppression and/or biologic therapy. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are widely used in the management of SLE with current more rationalized treatment regimens optimizing the use of these agents while minimizing potential toxicity. The advent of biologic therapies has advanced the treatment of SLE particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are now widely in use in clinical practice. Several other biologic agents are in ongoing clinical trials. While immunosuppressive and biologic agents are the foundation of inflammatory disease control in SLE, the importance of managing comorbidities such as cardiovascular risk factors, bone health, and minimizing susceptibility to infection should not be neglected. PMID:27529058