Science.gov

Sample records for agent diethylenetriaminepentaacetic acid

  1. Preparation of alginate beads containing a prodrug of diethylenetriaminepentaacetic acid

    PubMed Central

    Yang, Yu-Tsai; Di Pasqua, Anthony J.; He, Weiling; Tsai, Tsuimin; Sueda, Katsuhiko; Zhang, Yong; Jay, Michael

    2012-01-01

    A penta-ethyl ester prodrug of the radionuclide decorporation agent diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was encapsulated in alginate beads by the ionotropic gelation method. An optimal formulation was found by varying initial concentrations of DTPA pentaethyl ester, alginate polymer, Tween 80 surfactant and calcium chloride. All prepared alginate beads were ~1.6 mm in diameter, and the optimal formulation had loading and encapsulation efficiencies of 91.0 ± 1.1 and 72.6 ± 2.2%, respectively, and only 3.2 ± 0.8% water absorption after storage at room temperature in ~80% relative humidity. Moreover, Fourier transform infrared spectroscopy showed that DTPA penta-ethyl ester did not react with excipients during formation of the DTPA penta-ethyl ester-containing alginate beads. Release of prodrug from alginate beads was via anomalous transport, and its stability enhanced by encapsulation. Collectively, these data suggest that this solid dosage form may be suitable for oral administration after radionuclide contamination. PMID:23399237

  2. Process for the manufacture of 117Sn diethylenetriaminepentaacetic acids

    DOEpatents

    Srivastava, Suresh C.; Li, Zizhong; Meinken, George

    2003-01-01

    Novel methods are provided for the manufacture of .sup.117m Sn(Sn.sup.4+) DTPA. The method allows the use of DTPA, a toxic chelating agent, in an approximately 1:1 ratio to .sup.117m Sn(Sn.sup.4+) via either aqueous conditions, or using various organic solvents, such as methylene chloride. A pharmaceutical composition manufactured by the novel method is also provided, as well as methods for treatment of bone tumors and pain associated with bone cancer using the pharmaceutical composition of the invention.

  3. Prospective evaluation of renal allograft dysfunction with 99mtechnetium-diethylenetriaminepentaacetic acid renal scans

    SciTech Connect

    McConnell, J.D.; Sagalowsky, A.I.; Lewis, S.E.; Gailiunas, P.; Helderman, J.H.; Dawidson, I.; Peters, P.C.

    1984-05-01

    A prospective, single-blinded study was done to determine the ability of serial 99mtechnetium-diethylenetriaminepentaacetic acid scans to diagnose renal allograft rejection. Among 28 transplant recipients 111 renal scans were obtained 1 day postoperatively and every 3 to 4 days thereafter for 3 weeks in all patients retaining an allograft. Computer-generated time-activity blood flow curves were analyzed semiquantitatively for the 1) interval between curve peaks of the allograft and iliac artery, 2) renal transit time and 3) renal washout of radionuclide. Excretory function was assessed by degree and interval to appearance of radionuclide in the calices and bladder. Deterioration of renal blood flow and excretion compared to the initial scan was considered rejection. Of 52 scans performed during clinical rejection 47 (90.4 per cent) were interpreted as showing rejection (sensitivity). Of 53 scans interpreted as showing rejection 47 (88.7 per cent) were positive for clinical rejection. The remaining 6 patients (initial false positive results) suffered clinical rejection within 24 to 72 hours. We conclude that 99mtechnetium-diethylenetriaminepentaacetic acid renal scans are useful in the differential diagnosis of renal allograft dysfunction.

  4. Thermodynamic, spectroscopic, and computational studies of lanthanide complexation with Diethylenetriaminepentaacetic acide: temperature effect and coordination modes

    SciTech Connect

    Guoxin Tian; Leigh R. Martin; Zhiyong Zhang; Linfeng Rao

    2011-04-01

    Stability constants of two DTPA (diethylenetriaminepentaacetic acid) complexes with lanthanides (ML2- and MHL-, where M stands for Nd and Eu and L stands for diethylenetriaminepentaacetate) at 10, 25, 40, 55, and 70 degrees C were determined by potentiometry, absorption spectrophotometry, and luminescence spectroscopy. The enthalpies of complexation at 25 degrees C were determined by microcalorimetry. Thermodynamic data show that the complexation of Nd3þ and Eu3þ with DTPA is weakened at higher temperatures, a 10-fold decrease in the stability constants of ML2- and MHL- as the temperature is increased from 10 to 70 degrees C. The effect of temperature is consistent with the exothermic enthalpy of complexation directly measured by microcalorimetry. Results by luminescence spectroscopy and density functional theory (DFT) calculations suggest that DTPA is octa-dentate in both the EuL2- and EuHL- complexes and, for the first time, the coordination mode in the EuHL- complex was clarified by integration of the experimental data and DFT calculations. In the EuHL- complex, the Eu is coordinated by an octa-dentate H(DTPA) ligand and a water molecule, and the protonation occurs on the oxygen of a carboxylate group.

  5. Separation Nanotechnology of Diethylenetriaminepentaacetic Acid Bonded Magnetic Nanoparticles for Spent Nuclear Fuel

    SciTech Connect

    Kaur, Maninder; Johnson, Andrew; Tian, Guoxin; Jiang, Weilin; Rao, Linfeng; Paszczynski, Andrzej; Qiang, You

    2013-01-01

    A nanomagnetic separation method based on Diethylenetriaminepentaacetic acid (DTPA) conjugated with magnetic nanoparticles (MNPs) is studied for application in spent nuclear fuel separation. The high affinity of DTPA towards actinides aids in separation from the highly acidic medium of nuclear waste. The solubility and magnetization of particles at low pH is protected by encapsulating them in silica layer. Surface functionalization of silica coated particles with polyamines enhances the loading capacity of the chelators on MNPs. The particles were characterized before and after surface modification using transmission electron microscopy (TEM), helium ion microscopy (HIM), Fourier transform-infrared (FT-IR) spectrometry, and X-ray diffractometry. The coated and uncoated samples were studied using vibrating sample magnetometer (VSM) to understand the change in magnetic properties due to the influence of the surface functionalization. The hydrodynamic size and surface charge of the particles are investigated using Dynamic Light Scattering (DLS). The uptake behavior of Am(III), Pu(IV), U(VI), and Np(V) from 0.1M NaNO3 solution was investigated. The sorption result shows the strong affinity of DTPA towards Am(III) and Pu(IV) by extracting 97% and 80% of actinides, respectively. The high removal efficiency and fast uptake of actinides make the chelator conjugated MNPs an effective method for spent nuclear fuel separation.

  6. Adsorption of chromium from aqueous solutions using crosslinked chitosan-diethylenetriaminepentaacetic acid.

    PubMed

    Bhatt, Ronak; Sreedhar, B; Padmaja, P

    2015-03-01

    Chitosan (CH) and its derivatives have been the focus of attention for researchers as potential adsorbents for heavy metal removal. The adsorption potential of chitosan cross-linked with diethylenetriaminepentaacetic acid (CD) for Cr6+ was investigated. CD was characterized by FTIR, XRD, TGA, XPS and ESR techniques. Batch experiments were conducted to optimize the parameters affecting the adsorption of chromium. The optimum pH was found to be 3 and the adsorption process was found to be exothermic. Adsorption isotherms were determined and the maximum adsorption capacity of CD for chromium was found to be 192.3 mg/g which was higher than the adsorption capacity of the adsorbents reported in literature. The thermodynamic parameters, such as Gibbs free energy, changes in enthalpy and changes in entropy change were also evaluated. XPS and ESR studies revealed that Cr6+ adsorbed onto CD was reduced to Cr3+. The efficacy of CD for removal of Cr6+ from chrome plating effluent was demonstrated.

  7. Rapid and sensitive determination of ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid in water samples by ion-pair reversed-phase liquid chromatography--electrospray tandem mass spectrometry.

    PubMed

    Quintana, José Benito; Reemtsma, Thorsten

    2007-03-23

    A new method is presented for the quantitative determination of ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) from aqueous samples without an enrichment step. It consist of the formation of the Fe(III) complexes of EDTA and DTPA, liquid-chromatography with a volatile ion-pairing agent and determination by electrospray ionization-tandem mass spectrometry (ESI-MS/MS). Limits of quantification (LOQ) of 1.0 and 0.6 microgL(-1) for EDTA and DTPA were obtained, allowing the direct injection of most aqueous environmental samples without any preceding enrichment. With a more recent mass spectrometer, the LOQ could be further decreased by almost one order of magnitude. Parallel analysis of real samples by a standardized method employing enrichment, derivatization and GC-MS analysis yielded comparable results. The method was applied to the determination of both complexing agents in several wastewater, surface water and drinking water samples, showing that EDTA is an omnipresent contaminant in partially closed water cycles.

  8. Comparative evaluation of glutamate-sensitive radiopharmaceuticals: Technetium-99m-glutamic acid and technetium-99m-diethylenetriaminepentaacetic acid-bis(glutamate) conjugate for tumor imaging.

    PubMed

    Kakkar, Dipti; Tiwari, Anjani K; Chuttani, Krishna; Kaul, Ankur; Singh, Harpal; Mishra, Anil K

    2010-12-01

    Single-photon emission computed tomography has become a significant imaging modality with huge potential to visualize and provide information of anatomic dysfunctions that are predictive of future diseases. This imaging tool is complimented by radiopharmaceuticals/radiosubstrates that help in imaging specific physiological aspects of the human body. The present study was undertaken to explore the utility of technetium-99m (⁹⁹(m)Tc)-labeled glutamate conjugates for tumor scintigraphy. As part of our efforts to further utilize the application of chelating agents, glutamic acid was conjugated with a multidentate ligand, diethylenetriaminepentaacetic acid (DTPA). The DTPA-glutamate conjugate [DTPA-bis(Glu)] was well characterized by IR, NMR, and mass spectroscopy. The biological activity of glutamic acid was compared with its DTPA conjugate by radiocomplexation with ⁹⁹(m)Tc (labeling efficiency ≥98%). In vivo studies of both the radiolabeled complexes ⁹⁹(m)Tc-Glu and ⁹⁹(m)Tc-DTPA-bis(Glu) were then carried out, followed by gamma scintigraphy in New Zealand albino rabbits. Improved serum stability of ⁹⁹(m)Tc-labeled DTPA conjugate indicated that ⁹⁹(m)Tc remained bound to the conjugate up to 24 hours. Blood clearance showed a relatively slow washout of the DTPA conjugate when compared with the labeled glutamate. Biodistribution characteristics of the conjugate in Balb/c mice revealed that DTPA conjugation of glutamic acid favors less accumulation in the liver and bone and rapid renal clearance. Tumor scintigraphy in mice showed increasing tumor accumulation, stable up to 4 hours. These preliminary studies show that ⁹⁹(m)Tc-DTPA-bis(Glu) can be a useful radiopharmaceutical for diagnostic applications in single-photon emission computed tomography imaging.

  9. Solid dispersions of the penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA): Formulation design and optimization studies

    PubMed Central

    Yang, Yu-Tsai; Di Pasqua, Anthony J.; Zhang, Yong; Sueda, Katsuhiko; Jay, Michael

    2015-01-01

    The penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was incorporated into a solid dispersion for oral administration by the solvent evaporation method using blends of polyvinylpyrrolidone (PVP), Eudragit® RL PO and α-tocopherol. D-optimal mixture design was used to optimize the formulation. Formulations that had a high concentration of both Eudragit® RL PO and α-tocopherol exhibited low water absorption and enhanced stability of the DTPA prodrug. Physicochemical properties of the optimal formulation were evaluated using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). In vitro release of the prodrug was evaluated using the USP Type II apparatus dissolution method. DSC studies indicated that the matrix had an amorphous structure, while FTIR spectrometry showed that DTPA penta-ethyl ester and excipients did not react with each other during formation of the solid dispersion.. Dissolution testing showed that the optimized solid dispersion exhibited a prolonged release profile, which could potentially result in a sustained delivery of DTPA penta-ethyl to enhance bioavailability. In conclusion, DTPA penta-ethyl ester was successfully incorporated into a solid matrix with high drug loading and improved stability compared to prodrug alone. PMID:24047113

  10. Spectrophotometric determination and removal of unchelated europium ions from solutions containing Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates.

    PubMed

    Elshan, N G R Dayan; Patek, Renata; Vagner, Josef; Mash, Eugene A

    2014-11-01

    Europium chelates conjugated with peptide ligands are routinely used as probes for conducting in vitro binding experiments. The presence of unchelated Eu ions in these formulations gives high background luminescence and can lead to poor results in binding assays. In our experience, the reported methods for purification of these probes do not achieve adequate removal of unchelated metal ions in a reliable manner. In this work, a xylenol orange-based assay for the quantification of unchelated metal ions was streamlined and used to determine levels of metal ion contamination as well as the success of metal ion removal on attempted purification. We compared the use of Empore chelating disks and Chelex 100 resin for the selective removal of unchelated Eu ions from several Eu-diethylenetriaminepentaacetic acid chelate-peptide conjugates. Both purification methods gave complete and selective removal of the contaminant metal ions. However, Empore chelating disks were found to give much higher recoveries of the probes under the conditions used. Related to the issue of probe recovery, we also describe a significantly more efficient method for the synthesis of one such probe using Rink amide AM resin in place of Tentagel S resin.

  11. Effects of positive expiratory pressure on pulmonary clearance of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid in healthy individuals

    PubMed Central

    de Albuquerque, Isabella Martins; Cardoso, Dannuey Machado; Masiero, Paulo Ricardo; Paiva, Dulciane Nunes; Resqueti, Vanessa Regiane; Fregonezi, Guilherme Augusto de Freitas; Menna-Barreto, Sérgio Saldanha

    2016-01-01

    ABSTRACT Objective: To evaluate the effects of positive expiratory pressure (PEP) on pulmonary epithelial membrane permeability in healthy subjects. Methods: We evaluated a cohort of 30 healthy subjects (15 males and 15 females) with a mean age of 28.3 ± 5.4 years, a mean FEV1/FVC ratio of 0.89 ± 0.14, and a mean FEV1 of 98.5 ± 13.1% of predicted. Subjects underwent technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) radioaerosol inhalation lung scintigraphy in two stages: during spontaneous breathing; and while breathing through a PEP mask at one of three PEP levels-10 cmH2O (n = 10), 15 cmH2O (n = 10), and 20 cmH2O (n = 10). The 99mTc-DTPA was nebulized for 3 min, and its clearance was recorded by scintigraphy over a 30-min period during spontaneous breathing and over a 30-min period during breathing through a PEP mask. Results: The pulmonary clearance of 99mTc-DTPA was significantly shorter when PEP was applied-at 10 cmH2O (p = 0.044), 15 cmH2O (p = 0.044), and 20 cmH2O (p = 0.004)-in comparison with that observed during spontaneous breathing. Conclusions: Our findings indicate that PEP, at the levels tested, is able to induce an increase in pulmonary epithelial membrane permeability and lung volume in healthy subjects. PMID:28117469

  12. An Evaluation of the Chelating Agent EDDS for Marigold Production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aminopolycarboxylic acid (APCA) ligands (chelating agents) like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are commonly used in soluble fertilizers to supply copper (Cu), iron (Fe), manganese (Mn), and/or zinc (Zn) to plants. The offsite runoff and contamina...

  13. Decorporation of systemically distributed americium by a novel orally administered diethylenetriaminepentaacetic acid (DTPA) formulation in beagle dogs.

    PubMed

    Wilson, James P; Cobb, Ronald R; Dungan, Nathanael W; Matthews, Laura L; Eppler, Bärbel; Aiello, Kenneth V; Curtis, Shiro; Boger, Teannetta; Guilmette, Raymond A; Weber, Waylon; Doyle-Eisele, Melanie; Talton, James D

    2015-03-01

    Novel decorporation agents are being developed to protect against radiological accidents and terrorists attacks. Radioactive americium is a significant component of nuclear fallout. Removal of large radioactive materials, such as 241Am, from exposed persons is a subject of significant interest due to the hazards they pose. The objective of this study was to evaluate the dose-related efficacy of daily doses of NanoDTPA™ Capsules for decorporating Am administered intravenously as a soluble citrate complex to male and female beagle dogs. In addition, the efficacy of the NanoDTPA™ Capsules for decorporating 241Am was directly compared to intravenously administered saline and DTPA. Animals received a single IV administration of 241Am(III)-citrate on Day 0. One day after radionuclide administration, one of four different doses of NanoDTPA™ Capsules [1, 2, or 6 capsules d(-1) (30 mg, 60 mg, or 180 mg DTPA) or 2 capsules BID], IV Zn-DTPA (5 mg kg(-1) pentetate zinc trisodium) as a positive control, or IV saline as a placebo were administered. NanoDTPA™ Capsules, IV Zn-DTPA, or IV saline was administered on study days 1-14. Animals were euthanized on day 21. A full necropsy was conducted, and liver, spleen, kidneys, lungs and trachea, tracheobronchial lymph nodes (TBLN), muscle samples (right and left quadriceps), gastrointestinal (GI) tract (stomach plus esophagus, upper and lower intestine), gonads, two femurs, lumbar vertebrae (L1-L4), and all other soft tissue remains were collected. Urinary and fecal excretion profiles were increased approximately 10-fold compared to those for untreated animals. Tissue contents were decreased compared to untreated controls. In particular, liver content was decreased by approximately eightfold compared to untreated animals. The results from this study further demonstrate that oral NanoDTPA™ Capsules are equally efficient compared to IV Zn-DTPA in decorporation of actinides.

  14. An Evaluation of the Chelating Agent EDDS for Floriculture Crop Production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aminopolycarboxylic acid (APCA) ligands (chelating agents) like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are commonly used in soluble fertilizers to supply copper (Cu), iron (Fe), manganese (Mn), and/or zinc (Zn) to plants. When complexed with Fe, EDTA and...

  15. Glutamic acid as anticancer agent: An overview.

    PubMed

    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.

  16. Nucleic acids as therapeutic agents.

    PubMed

    Alvarez-Salas, Luis M

    2008-01-01

    Therapeutic nucleic acids (TNAs) and its precursors are applied to treat several pathologies and infections. TNA-based therapy has different rationales and mechanisms and can be classified into three main groups: 1) Therapeutic nucleotides and nucleosides; 2) Therapeutic oligonucleotides; and 3) Therapeutic polynucleotides. This review will focus in those TNAs that have reached clinical trials with anticancer and antiviral protocols, the two most common applications of TNAs. Although therapeutic nucleotides and nucleosides that interfere with nucleic acid metabolism and DNA polymerization have been successfully used as anticancer and antiviral drugs, they often produce toxic secondary effects related to dosage and continuous use. The use of oligonucleotides such as ribozyme and antisense oligodeoxynucleotides (AS-ODNs) showed promise as therapeutic moieties but faced several issues such as nuclease sensitivity, off-target effects and efficient delivery. Nevertheless, immunostimulatory oligodeoxynucleotides and AS-ODNs represent the most successful group of therapeutic oligonucleotides in the clinic. A newer group of therapeutic oligonucleotides, the aptamers, is rapidly advancing towards early detection and treatment alternatives the have reached the commercial interest. Despite the very high in vitro efficiency of small interfering RNAs (siRNAs) they present issues with intracellular target accessibility, specificity and delivery. DNA vaccines showed great promise, but they resulted in very poor responses in the clinic and further development is uncertain. Despite their many issues, the exquisite specificity and versatility of therapeutic oligonucleotides attracts a great deal of research and resources that will certainly convert them in the TNA of choice for treating cancer and viral diseases in the near future.

  17. Formulation for Tin-.sup.117m /diethylenetriaminepentaacetic acids

    DOEpatents

    Srivastava, Suresh C.; Meinken, George E.

    1999-01-01

    The invention provides improved formulations of .sup.117m Sn (Sn.sup.4+) DTPA which allow higher doses of .sup.117m Sn (Sn.sup.4+) to be administered than were previously possible. Methods for making pharmaceutical compositions comprising .sup.117m Sn (Sn.sup.4+) DTPA in which the amount of unchelated DTPA is minimized are disclosed along with methods of using the improved formlulations, both for palliation of bone pain associated with cancer and for treatment of osseous tumors.

  18. Novel cajaninstilbene acid derivatives as antibacterial agents.

    PubMed

    Geng, Zhi-Zhong; Zhang, Jian-Jun; Lin, Jing; Huang, Mei-Yan; An, Lin-Kun; Zhang, Hong-Bin; Sun, Ping-Hua; Ye, Wen-Cai; Chen, Wei-Min

    2015-07-15

    Discovery of novel antibacterial agents with new structural scaffolds that combat drug-resistant pathogens is an urgent task. Cajaninstilbene acid, which is isolated from pigeonpea leaves, has shown antibacterial activity. In this study, a series of cajaninstilbene acid derivatives were designed and synthesized. The antibacterial activities of these compounds against gram-negative and gram-positive bacteria, as well as nine strains of methicillin-resistant staphylococcus aureus (MRSA) bacteria are evaluated,and the related structure-activity relationships are discussed. Assays suggest that some of the synthetic cajaninstilbene acid derivatives exhibit potent antibacterial activity against gram-positive bacterial strains and MRSA. Among these compounds, 5b, 5c, 5j and 5k show better antibacterial activity than the positive control compounds. The results of MTT assays illustrate the low cytotoxicity of the active compounds.

  19. Acetal phosphatidic acids: novel platelet aggregating agents.

    PubMed

    Brammer, J P; Maguire, M H; Walaszek, E J; Wiley, R A

    1983-05-01

    1 Palmitaldehyde, olealdehyde and linolealdehyde acetal phosphatidic acids induced rapid shape change and dose-dependent biphasic aggregation of human platelets in platelet-rich plasma; aggregation was reversible at low doses and irreversible at high doses of the acetal phosphatidic acids. The palmitaldehyde congener elicited monophasic dose-dependent aggregation of sheep platelets in platelet-rich plasma.2 The threshold concentration for palmitaldehyde acetal phosphatidic acid (PGAP)-induced platelet aggregation was 2.5-5 muM for human platelets and 0.25-0.5 muM for sheep platelets. PGAP was 4-5 times as potent versus human platelets as the olealdehyde and linolealdehyde acetal phosphatidic acids, which were equipotent.3 PGAP-induced irreversible aggregation of [(14)C]-5-hydroxytryptamine ([(14)C]-5-HT)-labelled human platelets in platelet-rich plasma was accompanied by release of 44.0+/-2.4% (s.e.) of the platelet [(14)C]-5-HT; reversible aggregation was not associated with release. In contrast, PGAP-induced release of [(14)C]-5-HT-labelled sheep platelets was dose-dependent.4 The adenosine diphosphate (ADP) antagonist, 2-methylthio-AMP, and the cyclo-oxygenase inhibitor, aspirin, abolished PGAP-induced second phase aggregation and release in human platelets but did not affect the first, reversible, phase of aggregation. Both the first and second phases of PGAP-induced aggregation were abolished by chlorpromazine, by the phospholipase A(2) inhibitor, mepacrine, and by nmolar concentrations of prostaglandin E(1) (PGE(1)); these agents abolished the second, but not the first phase of ADP-induced aggregation.5 The related phospholipids, lecithin, lysolecithin and phosphatidic acid, at <100 muM, neither induced aggregation of human platelets in platelet-rich plasma, nor modified PGAP-induced aggregation; 1-palmityl lysophosphatidic acid elicited aggregation of human platelets at a threshold concentration of 100 muM.6 It is concluded that the acetal phosphatidic acids

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:26347269

  2. Long-acting contraceptive agents: levonorgestrel esters of unsaturated acids.

    PubMed

    Wan, A S; Ngiam, T L; Leung, S L; Go, M L; Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; García, G A

    1983-03-01

    Esters of levonorgestrel (13 beta-ethyl-17 beta-ethynyl-17 beta-hydroxygon-4-en-3-one) with a variety of unsaturated carboxylic acids have been synthesized for evaluation as potential long-acting, injectable contraceptive agents.

  3. Nucleic acid in-situ hybridization detection of infectious agents

    NASA Astrophysics Data System (ADS)

    Thompson, Curtis T.

    2000-04-01

    Limitations of traditional culture methods and newer polymerase chain reaction (PCR)-based methods for detection and speciation of infectious agents demonstrate the need for more rapid and better diagnostics. Nucleic acid hybridization is a detection technology that has gained wide acceptance in cancer and prenatal cytogenetics. Using a modification of the nucleic acid hybridization technique known as fluorescence in-situ hybridization, infectious agents can be detected in a variety of specimens with high sensitivity and specificity. The specimens derive from all types of human and animal sources including body fluids, tissue aspirates and biopsy material. Nucleic acid hybridization can be performed in less than one hour. The result can be interpreted either using traditional fluorescence microscopy or automated platforms such as micro arrays. This paper demonstrates proof of concept for nucleic acid hybridization detection of different infectious agents. Interpretation within a cytologic and histologic context is possible with fluorescence microscopic analysis, thereby providing confirmatory evidence of hybridization. With careful probe selection, nucleic acid hybridization promises to be a highly sensitive and specific practical diagnostic alternative to culture, traditional staining methods, immunohistochemistry and complicated nucleic acid amplification tests.

  4. Long-acting contraceptive agents: norethisterone esters of polyunsaturated acids.

    PubMed

    Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; Vlahov, R; Tarpanov, V; Boshkova-Ljapova, M; Milenkov, B; Stoilova, V

    1983-03-01

    Some new derivatives of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) are described in which the 17 beta-hydroxyl group of the steroid is esterified with polyunsaturated aliphatic acids. The potential of these compounds as long-acting contraceptive agents has been evaluated.

  5. Enhancement of commercial antifungal agents by kojic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Kojic acid (KA), a natural by-product of fungal fermentation, is a commonly used food and cosmetic additive. We show that KA increases activity of amphotericin B and strobilurin, medical and agricultural antifungal agents, respectively, possibly targeting the fungal antioxidative system. KA shows pr...

  6. Degradability of fluorapatite-leucite ceramics in naturally acidic agents.

    PubMed

    Kukiattrakoon, Boonlert; Hengtrakool, Chanothai; Kedjarune-Leggat, Ureporn

    2010-10-01

    This study was conducted to evaluate the titratable acidity and effect of naturally acidic agents on the surface microhardness, elemental composition, and surface morphology of fluorapatite-leucite ceramics. One hundred and ten ceramic disks (IPS d.SIGN), 12.0 mm in diameter and 2.0 mm in thickness, were fabricated. Before immersion, the baseline data of Vickers microhardness and elemental composition were recorded. Four groups were immersed in acidic agents (citrate buffer solution, green mango juice, and pineapple juice) and deionized water (control) at 37ºC for 168 hours, whereas one group was immersed in 4% acetic acid at 80ºC for 168 hours. After immersion, specimens were evaluated and data were analyzed using one-way repeated ANOVA and Tukey's test (α=0.05). Microhardness values significantly decreased after immersion (p<0.05). In terms of elemental composition, the weight percentages of silicon, potassium, aluminum, and sodium also decreased after immersion (p<0.05). Results of this study showed that fluorapatite-leucite ceramics were affected by long-term immersion in acidic agents.

  7. Lewis acid-assisted detection of nerve agents in water.

    PubMed

    Butala, Rahul R; Creasy, William R; Fry, Roderick A; McKee, Michael L; Atwood, David A

    2015-06-07

    The five-coordinate compound, Salen((t)Bu)Al(Ac), prepared in situ from Salen((t)Bu)AlBr and NH4Ac, forms Lewis acid-base adducts in aqueous solution with the G-type nerve agents, Sarin and Soman, and the VX hydrolysis product, ethylmethylphosphonate (EMPA). The resulting compounds, [Salen((t)Bu)Al(NA)](+)[Ac] (-) (with NA = Sarin, Soman, and EMPA) are sufficiently stable to be identified by ESI-MS. Molecular ion peaks were detected for every compound with little or no fragmentation. The distinctive MS signatures for the [Salen((t)Bu)Al(NA)](+) compounds provide a new technique for identifying nerve agents from aqueous solution. The energetics of the displacement of Ac(-) by the nerve agents to form [Salen((t)Bu)Al(NA)](+)[Ac](-) were determined computationally.

  8. The use of glycolic acid as a peeling agent.

    PubMed

    Murad, H; Shamban, A T; Premo, P S

    1995-04-01

    Glycolic acid is a member of the AHA family, which occurs naturally in foods and has been used for centuries as a cutaneous rejuvenation treatment. Recently it has proved to be a versatile peeling agent and it is now widely used to treat many defects of the epidermis and papillary dermis in a variety of strengths, ranging from 20% to 70%, depending on the condition being treated. People of almost any skin type and color are candidates, and almost any area of the body can be peeled. Several weeks prior to a peel the skin may be prepared with topical tretinoin or glycolic acid, and immediately prior to the peel the skin may be degreased with a variety of agents. Following the peel the skin is carefully observed for any complications such as hyperpigmentation and infection. Results are maintained with serial peels and at-home use of tretinoin or glycolic acid, as well as sun avoidance. The glycolic acid can be applied simultaneously with TCA and is another technique for a medium-depth peel. Comparison of 35% TCA-treated skin with 70% glycolic acid-treated skin examined histologically at different times reveals similar changes in papillary dermis connective tissue proteins, epidermal necrosis seen only with TCA, and reversion at 2 years postpeel to pretreatment appearance.

  9. Quantitative measurement of regional blood flow with gadolinium diethylenetriaminepentaacetate bolus track NMR imaging in cerebral infarcts in rats: validation with the iodo[14C]antipyrine technique.

    PubMed Central

    Wittlich, F; Kohno, K; Mies, G; Norris, D G; Hoehn-Berlage, M

    1995-01-01

    NMR bolus track measurements were correlated with autoradiographically determined regional cerebral blood flow (rCBF). The NMR method is based on bolus infusion of the contrast agent gadolinium diethylenetriaminepentaacetate and high-speed T*2-sensitive NMR imaging. The first pass of the contrast agent through the image plane causes a transient decrease of the signal intensity. This time course of the signal intensity is transformed into relative concentrations of the contrast agent in each pixel. The mean transit time and relative blood flow and volume are calculated from such indicator dilution curves. We investigated whether this NMR technique correctly expresses the relative rCBF. The relative blood flow data, calculated from NMR bolus track experiments, and the absolute values of iodo[14C]antipyrine autoradiography were compared. A linear relationship was observed, indicating the proportionality of the transient NMR signal change with CBF. Excellent interindividual reproducibility of calibration constants is observed (r = 0.963). For a given NMR protocol, bolus track measurements calibrated with autoradiography after the experiment allow determination of absolute values for rCBF and regional blood volume. Images Fig. 2 Fig. 3 PMID:7892189

  10. Cancer preventive agents 9. Betulinic acid derivatives as potent cancer chemopreventive agents.

    PubMed

    Nakagawa-Goto, Kyoko; Yamada, Koji; Taniguchi, Masahiko; Tokuda, Harukuni; Lee, Kuo-Hsiung

    2009-07-01

    C-3 esterifications of betulinic acid (BA, 1) and its A-ring homolog, ceanothic acid (CA, 2), were carried out to provide sixteen terpenoids, 4-19, including nine new compounds (4-12). All synthesized compounds were evaluated in an in vitro antitumor-promoting assay using the Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. Among them, compounds 4-6, 11-14, 16, and 17 displayed remarkable inhibitory effects of EBV-EA activation. BA analog 6, which contains a prenyl-like group, showed the most potent inhibitory effect (100%, 76%, 37%, and 11% inhibition of EBA activation at 1000, 500, 100, and 10mol ratio/TPA, respectively, with IC(50) value of 285mol ratio/32pmol TPA). Compound 6 merits further development as a cancer preventive agent.

  11. Gradual surface degradation of restorative materials by acidic agents.

    PubMed

    Hengtrakool, Chanothai; Kukiattrakoon, Boonlert; Kedjarune-Leggat, Ureporn

    2011-01-01

    The aim of this study was to investigate the effect of acidic agents on surface roughness and characteristics of four restorative materials. Fifty-two discs were created from each restorative material: metal-reinforced glass ionomer cement (Ketac-S), resin-modified glass ionomer cement (Fuji II LC), resin composite (Filtek Z250), and amalgam (Valiant-PhD); each disc was 12 mm in diameter and 2.5 mm thick. The specimens were divided into four subgroups (n=13) and immersed for 168 hours in four storage media: deionized water (control); citrate buffer solution; green mango juice; and pineapple juice. Surface roughness measurements were performed with a profilometer, both before and after storage media immersion. Surface characteristics were examined using scanning electron microscopy (SEM). Statistical significance among each group was analyzed using two-way repeated ANOVA and Tukey's tests. Ketac-S demonstrated the highest roughness changes after immersion in acidic agents (p<0.05), followed by Fuji II LC. Valiant-PhD and Filtek Z250 illustrated some minor changes over 168 hours. The mango juice produced the greatest degradation effect of all materials tested (p<0.05). SEM photographs demonstrated gradual surface changes of all materials tested after immersions. Of the materials evaluated, amalgam and resin composite may be the most suitable for restorations for patients with tooth surface loss.

  12. Surface characteristic changes of dental ceramics after cyclic immersion in acidic agents and titratable acidity.

    PubMed

    Junpoom, Peerapong; Kukiattrakoon, Boonlert; Hengtrakool, Chanothai

    2010-12-01

    The potential erosive effect of acidic food, sour fruits and drinks on all-ceramic restorations used in dentistry has not been clearly documented. Surface characteristic changes have been evaluated and compared for disc-shaped specimens (diameter 12.0 mm and thickness 2.0 mm) of fluorapatite-leucite and fluorapatite ceramics using various storage agents (deionized water, citrate buffer solution, pineapple juice, green mango juice, cola soft drink and 4% acetic acid). Immersion in pineapple juice, green mango juice, cola soft drink and 4% acetic acid for 16 hours produce significant increases in surface roughness for both types of ceramics investigated.

  13. Theophylline-7-acetic acid derivatives with amino acids as anti-tuberculosis agents.

    PubMed

    Voynikov, Yulian; Valcheva, Violeta; Momekov, Georgi; Peikov, Plamen; Stavrakov, Georgi

    2014-07-15

    A series of amides were synthesized by condensation of theophylline-7-acetic acid and eight commercially available amino acid methyl ester hydrochlorides. Consecutive hydrolysis of six of the amido-esters resulted in the formation of corresponding amido-acids. The newly synthesized compounds were evaluated for their in vitro activity against Mycobacterium tuberculosis H37Rv. The activity varied depending on the amino acid fragments and in seven cases exerted excellent values with MICs 0.46-0.26 μM. Assessment of the cytotoxicity revealed that the compounds were not cytotoxic against the human embryonal kidney cell line HEK-293T. The theophylline-7-acetamides containing amino acid moieties appear to be promising lead compounds for the development of antimycobacterial agents.

  14. Thermodynamic study of the complexation of protactinium(V) with diethylenetriaminepentaacetic acid.

    PubMed

    Mendes, Mickaël; Leguay, Sébastien; Le Naour, Claire; Hamadi, Séna; Roques, Jérôme; Moisy, Philippe; Guillaumont, Dominique; Topin, Sylvain; Aupiais, Jean; Den Auwer, Christophe; Hennig, Christoph

    2013-07-01

    The complex formation of protactinium(V) with DTPA was studied at different temperatures (25-50 °C) and ionic strengths (0.1-1 M) with the element at tracer scale. Irrespective of the temperature and ionic strength studied, only one neutral complex with (1:1) stoichiometry was identified from solvent extraction and capillary electrophoresis coupled to ICP-MS (CE-ICP-MS) experiments. Density Functional Theory (DFT) calculations revealed that two complexes can be considered: Pa(DTPA) and PaO(H2DTPA). The associated formation constants were determined from solvent extraction data at different ionic strengths and temperatures and then extrapolated to zero ionic strength by SIT methodology. These constants are valid, regardless of complex form, Pa(DTPA) or PaO(H2DTPA). The standard thermodynamic data determined with these extrapolated constants revealed a very stable complex formed energetically by an endothermic contribution which is counter balanced by a strong entropic contribution. Both, the positive enthalpy and entropy energy terms suggest the formation of an inner sphere complex.

  15. Cholesterol-diethylenetriaminepentaacetate complexed with thulium ions integrated into bicelles to increase their magnetic alignability.

    PubMed

    Liebi, Marianne; Kuster, Simon; Kohlbrecher, Joachim; Ishikawa, Takashi; Fischer, Peter; Walde, Peter; Windhab, Erich J

    2013-11-27

    Lanthanides have been used for several decades to increase the magnetic alignability of bicelles. DMPE-DTPA (1,2-dimyristoyl-sn-glycero-3-phospho-ethanolamine-diethylenetriaminepentaacetate) is commonly applied to anchor the lanthanides into the bicelles. However, because DMPE-DTPA has the tendency to accumulate at the highly curved edge region of the bicelles and if located there does not contribute to the magnetic orientation energy, we have tested cholesterol-DTPA complexed with thulium ions (Tm(3+)) as an alternative chelator to increase the magnetic alignability. Differential scanning calorimetric (DSC) measurements indicate the successful integration of cholesterol-DTPA into a DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine) bilayer. Cryo transmission electron microscopy and small-angle neutron scattering (SANS) measurements show that the disklike structure, that is, bicelles, is maintained if cholesterol-DTPA·Tm(3+) is integrated into a mixture of DMPC, cholesterol, and DMPE-DTPA·Tm(3+). The size of the bicelles is increased compared to the size of the bicelles obtained from mixtures without cholesterol-DTPA·Tm(3+). Magnetic-field-induced birefringence and SANS measurements in a magnetic field show that with addition of cholesterol-DTPA·Tm(3+) the magnetic alignability of these bicelles is significantly increased compared to bicelles composed of DMPC, cholesterol, and DMPE-DTPA·Tm(3+) only.

  16. Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several benzoic acid analogs showed antifungal activity against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis. Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids increased by addition of a methyl, methoxyl...

  17. Biodegradable chelating agents for industrial, domestic, and agricultural applications--a review.

    PubMed

    Pinto, Isabel S S; Neto, Isabel F F; Soares, Helena M V M

    2014-10-01

    Aminopolycarboxylates, like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA), are chelating agents widely used in several industrial, agricultural, and domestic applications. However, the fact that they are not biodegradable leads to the presence of considerable amounts in aquatic systems, with serious environmental consequences. The replacement of these compounds by biodegradable alternatives has been the object of study in the last three decades. This paper reviews the most relevant studies towards the use of environmentally friendly chelating agents in a large number of applications: oxidative bleaching, detergents and cleaning compositions, scale prevention and reduction, remediation of soils, agriculture, electroplating, waste treatment, and biocides. Nitrilotriacetic acid (NTA), ethylenediaminedisuccinic acid (EDDS), and iminodisuccinic acid (IDS) are the most commonly suggested to replace the nonbiodegradable chelating agents. Depending on the application, the requirements for metal complexation might differ. Metal chelation ability of the most promising compounds [NTA, EDDS, IDS, methylglycinediacetic acid (MGDA), L-glutamic acid N,N-diacetic acid (GLDA), ethylenediamine-N,N'-diglutaric acid (EDDG), ethylenediamine-N,N'-dimalonic acid (EDDM), 3-hydroxy-2,2-iminodisuccinic acid (HIDS), 2-hydroxyethyliminodiacetic acid (HEIDA), pyridine-2,6-dicarboxylic acid (PDA)] with Fe, Mn, Cu, Pb, Cd, Zn, Ca, and Mg was simulated by computer calculations. The advantages or disadvantages of each compound for the most important applications were discussed.

  18. Cationic technetium-99m complexes of N-substituted pyridoxal derivatives as renal function agents

    SciTech Connect

    Karube, Yoshiharu; Iwamoto, Koji; Takata, Jiro

    1994-10-01

    New cationic technetium-chelating agents containing a pyridinium group have been synthesized and evaluated as potential renal radiopharmaceuticals. The pyridinium compounds used in the study are N-methyl pyridoxal chloride, N-ethyl pyridoxal chloride, N-propyl pyridoxal chloride, 1-methyl-3-hydroxy-4-formylpyridinium chloride, 1-methyl-2-formyl-3-hydroxpyridinium chloride and the Schiff`s bases of N-methyl pyridoxal chloride with amino acid, amino acid ester and amino acid amide. Complexes of these chelating agents with {sup 22m}Tc were prepared using a Na{sub 2}S{sub 2}O{sub 4} or a SnCl{sub 2} solution as a reducing agent. The purity of the {sup 99m}Tc complexes was determined by paper electrophoresis in 0.1 Mtris buffer. Electrophoresis indicates slightly positive-charged species. The log P values of these complexes showed a hydrophilic nature. Urinary excretion of the {sup 99m}Tc N-alkylated pyridoxal derivatives, {sup 99m}Tc-diethylenetriaminepentaacetic acid, {sup 99m}Tc-mercaptoacetylglycylglycylglycine (MAG3) and {sup 131}I-o-iodohippurate were determined in mice and rats at different time intervals. In a rat model, the pyridoxal-derived {sup 99m}Tc complexes are rapidly excreted in urine and provide clear renal scintigrams. Hepatobiliary excretion was negligible, reducing scan interference from the intestines. Total clearances were lower than that of {sup 131}I-hippurate and {sup 99m}Tc-MAG3. The rate of urinary clearance of the new tracers was not significantly faster than {sup 99m}Tc diethylenetriaminepentaacetic acid and the inhibitor N{sup 1}-methylnicotinamide had only a minimal effect on the renal behavior. Though the new tracers have cationic properties, the pyridinium group did not contribute largely to the excretion of active transport. 21 refs., 4 figs., 4 tabs.

  19. Synthesis of amino Derivatives of Dithio Acids as Potential Radiation Protective Agents

    DTIC Science & Technology

    1984-08-01

    ation Management S SI ____ K> AD Synthesis of Amino Derivatives of Dithio Acids as Potential Radiation Protective Agents * 0 Annual Report "TIi: o DTIC...Sftcuntiy Clatuftcatio") Synthesis of Amino Derivatives of Dithio Acids as PotentitI- Radiation Protective Agents 12l PERISONAL. Ak.TI4OR(S) * William...methyl- picoline derivatives was accomplished. Use of N-mthyl-2,6-dimethylpyridine also allowed the synthesis of a bis(dithioacetic acid) function not

  20. Augmenting the activity of antifungal agents against aspergilli using structural analogues of benzoic acid as chemosensitizing agents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Structure-activity analysis revealed that antifungal activities of benzoic and gallic acids were increased against strains of Aspergillus flavus, A. fumigatus and A. terreus, causative agents of human aspergillosis, by addition of a methyl, methoxyl or a chloro group at position 4 of the aromatic ri...

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

    NASA Astrophysics Data System (ADS)

    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

  2. Long-acting contraceptive agents: testosterone esters of unsaturated acids.

    PubMed

    Francisco, C G; Freire, R; Gawronski, J; Hernández, R; Kielczewski, M; Salazar, J A; Savabi, F; Shafiee, A; Strekowski, L; Suárez, E

    1990-01-01

    The synthesis of 13 new esters of testosterone is described, with the esterifying acids bearing acetylenic, olefinic, or polyunsaturated functions in the chain, for evaluation as long-acting androgens.

  3. Mitigating the antimicrobial activities of selected organic acids and commercial sanitizers with various neutralizing agents.

    PubMed

    Park, Yoen Ju; Chen, Jinru

    2011-05-01

    This study was conducted to evaluate the abilities of five neutralizing agents, Dey-Engley (DE) neutralizing broth (single or double strength), morpholinepropanesulfonic acid (MOPS) buffer, phosphate-buffered saline (PBS), and sodium thiosulfate buffer, in mitigating the activities of acetic or lactic acid (2%) and an alkaline or acidic sanitizer (a manufacturer-recommended concentration) againt the cells of Shiga toxin-producing Escherichia coli (STEC; n = 9). To evaluate the possible toxicity of the neutralizing agents to the STEC cells, each STEC strain was exposed to each of the neutralizing agents at room temperature for 10 min. Neutralizing efficacy was evaluated by placing each STEC strain in a mixture of sanitizer and neutralizer under the same conditions. The neutralizing agents had no detectable toxic effect on the STEC strains. PBS was least effective for neutralizing the activity of selected organic acids and sanitizers. Single-strength DE and sodium thiosulfate neutralized the activity of both acetic and lactic acids. MOPS buffer neutralized the activity of acetic acid and lactic acid against six and five STEC strains, respectively. All neutralizing agents, except double-strength DE broth, had a limited neutralizing effect on the activity of the commercial sanitizers used in the study. The double-strength DE broth effectively neutralized the activity of the two commercial sanitizers with no detectable toxic effects on STEC cells.

  4. Oleic acid-embedded nanoliposome as a selective tumoricidal agent.

    PubMed

    Jung, Sujin; Lee, Sangah; Lee, Hyejin; Yoon, Jaejin; Lee, E K

    2016-10-01

    HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cell), a molecular complex of human α-lactalbumin and oleic acid, is known to have selective cytotoxic activity against certain types of tumors. This cytotoxicity is known to stem from water-insoluble oleic acid. In this study, we manufactured an alternative complex using liposome as an oleic acid delivery vesicle. We named this nanolipoplex LIMLET (LIposome Made LEthal to Tumor cell). The LIMLET vesicle contained approximately 90,200 oleic acid molecules inserted into its lipophilic phospholipid bilayer and had a nominal mean diameter of 127nm. Using a WST-1 assay, its cytotoxicity against two cancer cell lines, MDA-MB-231 (human breast cancer) and A549 (human lung cancer), were tested. The results were compared with that of a normal cell line, Vero (from monkey kidney). We found that (1) LIMLET showed distinctive cytotoxicity against A549 and MDA-MB-231 cells, whereas bare liposomes (containing no oleic acid) had no toxicity, even at high concentrations, and (2) LIMLET demonstrated selective, concentration-dependent toxicity against the cancer cells: the LD50 values of MDA-MB-231 and A549 cells were 1.3 and 2.2nM LIMLET, respectively, whereas the LD50 of Vero was 5.7nM. The strength of the tumoricidal effect appeared to stem from the number of oleic acid molecules present. Our result suggests that LIMLET, like HAMLET, is an interesting nanolipoplex that can potentially be developed into tumor treatments.

  5. Morroniside cinnamic acid conjugate as an anti-inflammatory agent.

    PubMed

    Takeda, Yoshinori; Tanigawa, Naomi; Sunghwa, Fortunatus; Ninomiya, Masayuki; Hagiwara, Makoto; Matsushita, Kenji; Koketsu, Mamoru

    2010-08-15

    A morroniside cinnamic acid conjugate was prepared and evaluated on E-selectin mediated cell-cell adhesion as an important role in inflammatory processes. 7-O-Cinnamoylmorroniside exhibited excellent anti-inflammatory activity (IC(50)=49.3 microM) by inhibiting the expression of E-selectin; further, it was more active than another cinnamic-acid-conjugated iridoid glycoside (harpagoside; IC(50)=88.2 microM), 7-O-methylmorroniside, and morroniside itself. As a result, 7-O-cinnamoylmorroniside was observed to be a potent inhibitor of TNF-alpha-induced E-selectin expression.

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

    PubMed Central

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

    2007-01-01

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

  7. Synthesis of Nucleic Acid and Protein in L Cells Infected with the Agent of Meningopneumonitis

    PubMed Central

    Schechter, Esther M.

    1966-01-01

    Schechter, Esther M. (The University of Chicago, Chicago, Ill.). Synthesis of nucleic acid and protein in L cells infected with the agent of meningopneumonitis. J. Bacteriol. 91:2069–2080. 1966.—Synthesis of deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein in uninfected L cells and in L cells infected with the meningopneumonitis agent was compared by measuring rates of incorporation of H3-cytidine and C14-lysine into nuclear, cytoplasmic, and agent fractions in successive 5-hr periods during the meningopneumonitis growth cycle. Synthesis of meningopneumonitis DNA, RNA, and protein was first clearly evident in the labeling period 15 to 20 hr after infection, soon after initiation of agent multiplication. The rates of synthesis of agent DNA, RNA, and protein increased logarithmically for a brief period and then declined. However, rates of isotope incorporation into all three meningopneumonitis macromolecules were sustained at near maximal values throughout the remainder of the meningopneumonitis growth cycle. These data are most readily interpreted in terms of multiplication of the meningopneumonitis agent by binary fission. The L cell response to infection was a decreased rate of DNA and RNA synthesis and an accelerated rate of cell death. Host protein synthesis was unaffected. The inhibition of nucleic acid synthesis in infected L cells probably involved competition between host and parasite for nucleic acid precursors. Different sublines of L cells varied greatly in the degree to which their nucleic acid-synthesizing mechanisms were damaged by infection. The cytoplasm of infected L cells contained newly synthesized DNA and RNA that could not be accounted for as intact meningopneumonitis cells. This nucleic acid probably arose from disintegration of the fragile intracellular forms of the meningopneumonitis agent. Images PMID:5937251

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

    PubMed

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

    2007-09-15

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

  9. Inhibition of succinic acid production in metabolically engineered Escherichia coli by neutralizing agent, organic acids, and osmolarity.

    PubMed

    Andersson, Christian; Helmerius, Jonas; Hodge, David; Berglund, Kris A; Rova, Ulrika

    2009-01-01

    The economical viability of biochemical succinic acid production is a result of many processing parameters including final succinic acid concentration, recovery of succinate, and the volumetric productivity. Maintaining volumetric productivities >2.5 g L(-1) h(-1) is important if production of succinic acid from renewable resources should be competitive. In this work, the effects of organic acids, osmolarity, and neutralizing agent (NH4OH, KOH, NaOH, K2CO3, and Na2CO3), and Na2CO3) on the fermentative succinic acid production by Escherichia coli AFP184 were investigated. The highest concentration of succinic acid, 77 g L(-1), was obtained with Na2CO3. In general, irrespective of the base used, succinic acid productivity per viable cell was significantly reduced as the concentration of the produced acid increased. Increased osmolarity resulting from base addition during succinate production only marginally affected the productivity per viable cell. Addition of the osmoprotectant glycine betaine to cultures resulted in an increased aerobic growth rate and anaerobic glucose consumption rate, but decreased succinic acid yield. When using NH4OH productivity completely ceased at a succinic acid concentration of approximately 40 g L(-1). Volumetric productivities remained at 2.5 g L(-1) h(-1) for up to 10 h longer when K- or Na-bases where used instead of NH4OH. The decrease in cellular succinic acid productivity observed during the anaerobic phase was found to be due to increased organic acid concentrations rather than medium osmolarity.

  10. Pectin functionalized with natural fatty acids as antimicrobial agent.

    PubMed

    Calce, Enrica; Mignogna, Eleonora; Bugatti, Valeria; Galdiero, Massimiliano; Vittoria, Vittoria; De Luca, Stefania

    2014-07-01

    Several pectin derivatives were prepared by chemical modifications of the polysaccharide with natural fatty acids. The obtained biodegradable pectin-based materials, pectin-linoleate, pectin-oleate and pectin-palmitate, were investigated for their antimicrobial activity against several bacterial strains, Staphylococcus aureus and Escherichia coli. Good results were obtained for pectin-oleate and pectin-linoleate, which inhibit the growth of the selected microorganisms by 50-70%. They exert the better antimicrobial activity against S. aureus. Subsequently, the pectin-oleate and the pectin-linoleate samples were coated on polyethylene films and were assessed for their capacity to capture the oxygen molecules, reducing its penetration into the polymeric support. These results confirmed a possible application of the new materials in the field of active food packaging.

  11. A Potent, Versatile Disulfide-Reducing Agent from Aspartic Acid

    PubMed Central

    2013-01-01

    Dithiothreitol (DTT) is the standard reagent for reducing disulfide bonds between and within biological molecules. At neutral pH, however, >99% of DTT thiol groups are protonated and thus unreactive. Herein, we report on (2S)-2-amino-1,4-dimercaptobutane (dithiobutylamine or DTBA), a dithiol that can be synthesized from l-aspartic acid in a few high-yielding steps that are amenable to a large-scale process. DTBA has thiol pKa values that are ∼1 unit lower than those of DTT and forms a disulfide with a similar E°′ value. DTBA reduces disulfide bonds in both small molecules and proteins faster than does DTT. The amino group of DTBA enables its isolation by cation-exchange and facilitates its conjugation. These attributes indicate that DTBA is a superior reagent for reducing disulfide bonds in aqueous solution. PMID:22353145

  12. Thermoresponsive Acidic Microgels as Functional Draw Agents for Forward Osmosis Desalination.

    PubMed

    Hartanto, Yusak; Zargar, Masoumeh; Wang, Haihui; Jin, Bo; Dai, Sheng

    2016-04-19

    Thermoresponsive microgels with carboxylic acid functionalization have been recently introduced as an attractive draw agent for forward osmosis (FO) desalination, where the microgels showed promising water flux and water recovery performance. In this study, various comonomers containing different carboxylic acid and sulfonic acid functional groups were copolymerized with N-isopropylacrylamide (NP) to yield a series of functionalized thermoresponsive microgels possessing different acidic groups and hydrophobicities. The purified microgels were examined as the draw agents for FO application, and the results show the response of water flux and water recovery was significantly affected by various acidic comonomers. The thermoresponsive microgel with itaconic acid shows the best overall performance with an initial water flux of 44.8 LMH, water recovery up to 47.2% and apparent water flux of 3.1 LMH. This study shows that the incorporation of hydrophilic dicarboxylic acid functional groups into the microgels leads to the enhancement on water adsorption and overall performance. Our work elucidates in detail on the structure-property relationship of thermoresponsive microgels in their applications as FO draw agents and would be beneficial for future design and development of high performance FO desalination.

  13. Remineralizing agents: effects on acid-softened enamel.

    PubMed

    Porcelli, H Bp; Maeda, F A; Silva, B R; Miranda, W G; Cardoso, P Ec

    2015-01-01

    This study sought to evaluate whether remineralizing toothpastes can protect acid-softened enamel against further erosive episodes. Fifty enamel slabs of bovine teeth with preformed erosion-like lesions were randomly assigned to 1 control and 4 experimental groups (n = 10): group 1, nanohydroxyapatite (nanoHAp) dentifrice; group 2, arginine and calcium carbonate (CaCO3) dentifrice; group 3, potassium nitrate (KNO3) and high-fluoride (F) availability dentifrice; group 4, ordinary fluoridated dentifrice (OFD); and group 5, control (deionized water). Initial hardness measurements were taken after the different treatments were applied. Statistically significant mineral gains of 8.0% and 10.0% were exhibited in groups 1 and 4, respectively. Groups 2 and 3 showed mineral gains of 4.5% and 2.1%, respectively; these were not statistically significant. Group 5 showed mineral loss (-11.8%). A 1-way analysis of variance showed no statistically significant differences in the mean microhardness values among groups. However, there are indications that the nanoHAp and OFD toothpastes may decrease erosive lesions after treatment, while the arginine + CaCO3 and KNO3 + F pastes may prevent the progression of erosive lesions.

  14. Tranexamic Acid as Antifibrinolytic Agent in Non Traumatic Intracerebral Hemorrhages

    PubMed Central

    ARUMUGAM, Ananda; A RAHMAN, Noor Azman; THEOPHILUS, Sharon Casilda; SHARIFFUDIN, Ashraf; ABDULLAH, Jafri Malin

    2015-01-01

    Background: Mortality and morbidity associated with intracerebral hemorrhage is still high. Up to now, there are no evidence-based effective treatments for acute ICH. This study is to assess the effect of tranexamic acid (TXA) on hematoma growth of patients with spontaneous ICH compared to a placebo. Methods: We performed a single-blinded, randomised placebo-controlled trial of TXA (intravenous 1g bolus, followed by infusion TXA 1 g/hour for 8 hours) in acute (< 8 hours) primary ICH. Strict blood pressure control (target SBP 140-160 mmHg). A repeat Computed Tomography brain was done after 24 hours to reassess hematoma growth. The primary objective is to test the effect of TXA on hematoma growth. Other objective was to test the feasibility, tolerability, and adverse events of TXA in primary ICH. Results: Statistical analysis showed significant hematoma growth in control group after 24 hours compared to baseline (14.3300 vs 17.9940, P = 0.001) whereas the treatment group there is no significant hematoma size expansion between baseline and after 24 hours (P = 0.313). Conclusions: This study showed a significant hematoma volume expansion in the control group compared to the treatment group. PMID:27006639

  15. Characterization of radionuclide-chelating agent complexes found in low-level radioactive decontamination waste. Literature review

    SciTech Connect

    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.

  16. Synthesis and biological activity of thiazolyl-acetic acid derivatives as possible antimicrobial agents.

    PubMed

    Shirai, Akihiro; Fumoto, Yasuko; Shouno, Tomoaki; Maseda, Hideaki; Omasa, Takeshi

    2013-01-01

    5a-h, a series of (5-substituted-2-methyl-1,3-thiazole-4-yl) acetic acids as heterocyclic acetic acid derivatives, was designed and synthesized from ethyl acetoacetate. The synthesized compounds were screened for their antimicrobial activities against bacterial and fungal strains, and their characteristics were investigated by assays under various temperature and pH conditions. Cytotoxicity was evaluated with the use of sheep erythrocytes and human neonate dermal fibroblasts. Similarly, agents such as lauric acid 6 and parabens 7a-b, which are used as preservative agents for commercial cosmetics and detergents, were assayed for comparison. Although the structure of 5a is simple, comprising a thiazole attached with an octyl group and acetic acid moiety, the compound showed stronger and broader antibacterial and antifungal activities among the 5 series against the tested microbes other than gram-negative bacteria. Interestingly, 5a overcame the weak antifungal activity of parabens 7a-b. Also, the cytotoxicity of 5a was less than that of parabens 7a-b, especially to human dermal fibroblasts. These results suggest that thiazolyl-acetic acid 5a is a potentially effective biocide, and that it could be used as a preservative agent in commercially sold cosmetics and detergents, facilitated by the hydrophilic and charge properties of its carboxylic acid moiety.

  17. Comparison of the tumor-seeking agent Tc-99m(V) dimercaptosuccinic acid and the renal imaging agent Tc-99m dimercaptosuccinic acid in humans

    SciTech Connect

    Ohta, H.; Ishii, M.; Yoshizumi, M.; Endo, K.; Sakahara, H.; Nakajima, T.; Yomoda, I.; Masuda, H.; Horiuchi, K.; Hata, N.

    1985-03-01

    Being aware of the ideal nuclear properties of Tc-99m, interest has been focused on the design of the (+5) oxidation state Tc-99m(V) dimercaptosuccinic acid (Tc(V)-DMSA) as a tumor-seeking agent. Tc-99m(V) DMSA holds a TcO4(3-) core and, like PO4(3-), has excellent characteristics for tumor uptake, but has a different distribution than the well-known renal scanning agent, Tc-99m DMSA. The differences in chemical behavior of Tc-99m(V) DMSA and Tc-99m DMSA are discussed. Three cases in which neoplasms were studied with Tc-99m(V) DMSA and Tc-99m DMSA are presented. Tc-99m DMSA and Tc-99m(V) DMSA, having a common ligand and tracer but, with the metal ion core in a different oxidation state, the uptake characteristics are altered markedly.

  18. Long-acting contraceptive agents: norethisterone esters of monoalkenyl and monoalkynyl acids.

    PubMed

    Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; García de la Mora, G A; Noguez, J A; Acosta, A; Jimeno, O

    1983-03-01

    The synthesis of nine new esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) is described, with the esterifying acids bearing an acetylenic or olefinic function in a chain of eight or nine carbon atoms, for evaluation as long-acting contraceptive agents.

  19. Influence of polycarboxylic acid chelating agents on the kinetics of the dissolution of metal oxides

    SciTech Connect

    Dyatlova, N.M.; Gorichev, I.G.; Dukhanin, V.S.; Malov, L.V.

    1986-11-01

    The factors influencing the rate of dissolution of metal oxides in aqueous solutions of acids in the presence of polycarboxylic acid chelating agents and other complexing agents have been quantitatively compared in this review, and the decisive role of the gradient of protons and electrons in the realization of this process has been revealed. The main hypotheses of the proposed conceptions of the electron-proton theory for the dissolution of metal oxides have been stated: 1) The rate-limiting step is charge transfer (first hypothesis); 2) The rate limiting step is the desorption of the dissolution products (second hypothesis). The applicability of the proposed electron-proton theory to the theoretical substantiation of all the experimentally observed kinetic features of the influence of various factors has been demonstrated. Practical recommendations for the effective utilization of the chelating agents considered for removing iron oxide surface deposits have been given.

  20. Salicylic acid and some of its derivatives as antibacterial agents for viscose fabric.

    PubMed

    Kantouch, A; El-Sayed, A Atef; Salama, M; El-Kheir, A Abou; Mowafi, S

    2013-11-01

    Salicylic acid and three of its derivatives were used to provide antibacterial properties to viscose fabrics. The four bactericides used were bonded to the viscose fabrics using epichlorohydrin or polymer binders. Optimization of the salicylic acid and its derivatives as well as the concentration of polymers was reported. The ability of the polymer binders to attract and bind the four bactericides was observed. The overall results show that the antibacterial reactivity of salicylic acid and its derivatives are in the following order 5-bromosalicylic acid>salicylic acid>5-chlorosalicylic acid>4-chlorosalicylic acid. Using epichlorohydrin as a binding agent, unfortunately, inhibits the bactericidal activity of the four bactericides. The FTIR study concludes that the reaction between salicylic acid as well as its derivatives with epichlorohydrin takes place through the phenolic group of the acids. The unexpected deterioration in the bactericidal properties of salicylic acid and its derivatives as a result of the treatment with epichlorohydrin could be due to the nature of interaction between the epichlorohydrin molecule and the acids molecules. PVP and PU show superior ability to sustain the four bactericides used even after 10 washing cycles.

  1. Dysprosium(III)-diethylenetriaminepentaacetate complexes of aminocyclodextrins as chiral NMR shift reagents.

    PubMed

    Wenzel, T J; Miles, R D; Zomlefer, K; Frederique, D E; Roan, M A; Troughton, J S; Pond, B V; Colby, A L

    2000-01-01

    A metal chelating ligand is bonded to alpha-, beta-, and gamma-cyclodextrin by the reaction of diethylenetraminepentaacetic dianhydride with the corresponding 6-mono- and 2-mono(amine)cyclodextrin. Adding Dy(III) to the cyclodextrin derivatives causes shifts in the (1)H-NMR spectra of substrates such as propranolol, tryptophan, aspartame, carbinoxamine, pheniramine, doxylamine, and 1-anilino-8-naphthalenesulfonate. The Dy(III)-induced shifts enhance the enantiomeric resolution in the NMR spectra of several substrates. Enhancements in enantiomeric resolution using cyclodextrin derivatives with the amine tether are compared to previously described compounds in which the chelating ligand is attached through an ethylenediamine tether. In general, the Dy(III) complex of the 6-beta-derivative with the amine tether is a more effective chiral resolving agent than the complex with the ethylenediamine tether. The opposite trend is observed with the 2-beta-derivatives. The presence of the chelating ligand in the 2-beta-derivative hinders certain substrates from entering the cavity. For cationic substrates, evidence suggests that a cooperative association involving inclusion in the cavity and association with the Dy(III) unit occurs. Enhancements in enantiomeric resolution in the spectrum of tryptophan are greater for the secondary alpha- and gamma-derivatives than the beta-derivative.

  2. Agents.

    PubMed

    Chambers, David W

    2002-01-01

    Although health care is inherently an economic activity, it is inadequately described as a market process. An alternative, grounded in organizational economic theory, is to view professionals and many others as agents, contracted to advance the best interests of their principals (patients). This view untangles some of the ethical conflicts in dentistry. It also helps identify major controllable costs in dentistry and suggests that dentists can act as a group to increase or decrease agency costs, primarily by controlling the bad actors who damage the value of all dentists.

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  5. Biological agent identification by nucleic acid base-pair analysis using surface-enhanced Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Farquharson, Stuart; Smith, Wayne W.; Elliott, Susan; Sperry, Jay F.

    1999-01-01

    Recently, a number of analytical methods have been successfully developed which use nucleic acid sequencing to identify biological warfare agents. However, the effectiveness of these methods, towards the safety and protection of US Armed Forces and their allies are limited by the period required to enumerate the nucleic acid through polymerase chain reactions or culture growth to produce sufficient quantities for analysis. To overcome this limitation, we have been investigating the ability of surface-enhanced Raman spectroscopy to detect nucleic acids with sufficient sensitivity and selectivity to eliminate the need for enumeration. The design of a small volume electrolytic sample cell will be presented along with analysis of the nucleic acid bases and preliminary analysis of model bacteria.

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

    PubMed

    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.

  7. 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

    PubMed Central

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

    2017-01-01

    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. PMID:28299301

  8. Plant-derived antifungal agent poacic acid targets β-1,3-glucan

    DOE PAGES

    Piotrowski, Jeff S.; Okada, Hiroki; Lu, Fachuang; ...

    2015-03-09

    A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole.more » The cellular target was identified; poacic acid localized to the cell wall and inhibited β-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding β-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range fungal pathogen S. sclerotiorum substantially reduced lesion development. In conclusion, the discovery of poacic acid as a natural antifungal agent targeting β-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates.« less

  9. Plant-derived antifungal agent poacic acid targets β-1,3-glucan

    SciTech Connect

    Piotrowski, Jeff S.; Okada, Hiroki; Lu, Fachuang; Li, Sheena C.; Hinchman, Li; Ranjan, Ashish; Smith, Damon L.; Higbee, Alan J.; Ulbrich, Arne; Coon, Joshua J.; Deshpande, Raamesh; Bukhman, Yury V.; McIlwain, Sean; Ong, Irene M.; Myers, Chad L.; Boone, Charles; Landick, Robert; Ralph, John; Kabbage, Mehdi; Ohya, Yoshikazu

    2015-03-09

    A rise in resistance to current antifungals necessitates strategies to identify alternative sources of effective fungicides. We report the discovery of poacic acid, a potent antifungal compound found in lignocellulosic hydrolysates of grasses. Chemical genomics using Saccharomyces cerevisiae showed that loss of cell wall synthesis and maintenance genes conferred increased sensitivity to poacic acid. Morphological analysis revealed that cells treated with poacic acid behaved similarly to cells treated with other cell wall-targeting drugs and mutants with deletions in genes involved in processes related to cell wall biogenesis. Poacic acid causes rapid cell lysis and is synergistic with caspofungin and fluconazole. The cellular target was identified; poacic acid localized to the cell wall and inhibited β-1,3-glucan synthesis in vivo and in vitro, apparently by directly binding β-1,3-glucan. Through its activity on the glucan layer, poacic acid inhibits growth of the fungi Sclerotinia sclerotiorum and Alternaria solani as well as the oomycete Phytophthora sojae. A single application of poacic acid to leaves infected with the broad-range fungal pathogen S. sclerotiorum substantially reduced lesion development. In conclusion, the discovery of poacic acid as a natural antifungal agent targeting β-1,3-glucan highlights the potential side use of products generated in the processing of renewable biomass toward biofuels as a source of valuable bioactive compounds and further clarifies the nature and mechanism of fermentation inhibitors found in lignocellulosic hydrolysates.

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

    PubMed

    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.

  11. Combination of amino acid/dipeptide with ligustrazine-betulinic acid as antitumor agents.

    PubMed

    Xu, Bing; Yan, Wen-Qiang; Xu, Xin; Wu, Gao-Rong; Zhang, Chen-Ze; Han, Yao-Tian; Chu, Fu-Hao; Zhao, Rui; Wang, Peng-Long; Lei, Hai-Min

    2017-04-21

    The lead compound TBA, 3β-Hydroxy-lup-20(29)-ene-28-oic acid-3, 5, 6-trimethylpyrazin-2-methyl ester, which exhibited promising antitumor activity and induced tumor cell apoptosis in various cancer cell lines, had previously been reported. Moreover, reports have revealed that the introduction of amino acid to betulinic acid could improve selective cytotoxicity as well as water solubility. Thus, a series of novel TBA amino acid and dipeptide derivatives were designed, synthesized and screened for selective cytotoxic activity against five cancer cell lines (HepG2, HT-29, Hela, BCG-823 and A549) and the not malignant cell line MDCK by standard MTT assay. Most of the tested TBA-amino acid and dipeptide analogues showed stronger anti-proliferative activity against all tested tumor cell lines than TBA. Among them, BA-25 exhibited the greatest cytotoxic activity on tumor cell lines (mean IC50 = 2.31 ± 0.78 μM), that was twofold than the positive drug cisplatin (DDP), while it showed lower cytotoxicity on MDCK cell line than DDP. Further cell apoptosis analyses indicated BA-25-induced apoptosis was associated with loss of mitochondrial membrane potential and increase of intracellular free Ca(2+) concentration.

  12. Acid-mediated formation of trifluoromethyl sulfonates from sulfonic acids and a hypervalent iodine trifluoromethylating agent.

    PubMed

    Koller, Raffael; Huchet, Quentin; Battaglia, Philip; Welch, Jan M; Togni, Antonio

    2009-10-28

    A variety of sulfonic acids have been trifluoromethylated using 1-trifluoromethyl-1,2-benziodoxol-3(1H)-one under mild conditions in good to excellent yields. Initial mechanistic investigations of this reaction show a clean second-order kinetics and only very weak substrate electronic effects.

  13. Nucleic Acid-directed Self-assembly of Multifunctional Gold Nanoparticle Imaging Agents1

    PubMed Central

    Zhang, Ziyan; Liu, Yongjian; Jarreau, Chad; Welch, Michael J.; Taylor, John-Stephen A.

    2013-01-01

    Gold nanoparticles have attracted much interest as a platform for development of multifunctional imaging and therapeutic agents. Multifunctionalized gold nanoparticles are generally constructed by covalent assembly of a gold core with thiolated ligands. In this study, we have assembled multifunctionalized gold nanoparticles in one step by nucleic acid hybridization of ODN (oligodeoxynucleotide)-derivatized gold nanoparticles with a library of pre-functionalized complementary PNAs (peptide nucleic acids). The PNAs were functionalized by conjugation with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) for chelating 64Cu for PET imaging, PEG (polyethylene glycol) for conferring stealth properties, and Cy5 for fluorescent imaging. The resulting nanoparticles showed good stability both in vitro and in vivo showing biodistribution behavior in a mouse that would be expected for a PEGylated gold nanoparticle rather than that for the radiolabelled PNA used in its assembly. PMID:24058728

  14. Amino acid derivatives of ligustrazine-oleanolic acid as new cytotoxic agents.

    PubMed

    Chu, Fuhao; Xu, Xin; Li, Guoliang; Gu, Shun; Xu, Kuo; Gong, Yan; Xu, Bing; Wang, Mina; Zhang, Huazheng; Zhang, Yuzhong; Wang, Penglong; Lei, Haimin

    2014-11-07

    A series of novel ligustrazine-oleanolic acid (TOA) derivatives were designed, and synthesized by conjugating amino acids to the 3-hydroxy group of TOA by ester bonds. Their cytotoxicity was evaluated on four cancer cell lines (HepG2, HT-29, Hela and BGC-823) by standard MTT assays. The ClogP values were calculated by means of computer simulation, and logP values of both 3β-glycine ester olean-12-en-28-oic acid-3,5,6-trimethylpyrazin-2-methyl ester (6a) and TOA were determined using a shake flask-ultraviolet spectrophotometry method. It was found that 6a and the 3β-L-lysine ester-6g not only displayed good cytotoxicity (IC50<3.5 μM) but also possessed better hydrophilicity than TOA. Moreover, 6a (IC50=4.884 μM) had lower nephrotoxicity than both 6g (IC50=2.310 μM) and cisplatin (CDDP, IC50=3.691 μM) on MDCK cells. Combining Giemsa and DAPI staining, it was further verified that 6a could induce HepG2 apoptosis via nuclei fragmentation and had lower nephrotoxicity. In addition, the structure-activity relationships of these derivatives are briefly discussed.

  15. Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI.

    PubMed

    Doiron, Amber L; Chu, Kevin; Ali, Adeel; Brannon-Peppas, Lisa

    2008-11-11

    Accurate imaging of atherosclerosis is a growing necessity for timely treatment of the disease. Magnetic resonance imaging (MRI) is a promising technique for plaque imaging. The goal of this study was to create polymeric particles of a small size with high loading of diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) and demonstrate their usefulness for MRI. A water-in-oil-in-oil double emulsion solvent evaporation technique was used to encapsulate the MRI agent in a poly(lactide-co-glycolide) (PLGA) or polylactide-poly(ethylene glycol) (PLA-PEG) particle for the purpose of concentrating the agent at an imaging site. PLGA particles with two separate average sizes of 1.83 microm and 920 nm, and PLA-PEG particles with a mean diameter of 952 nm were created. Loading of up to 30 wt % Gd-DTPA was achieved, and in vitro release occurred over 5 h. PLGA particles had highly negative zeta potentials, whereas the particles incorporating PEG had zeta potentials closer to neutral. Cytotoxicity of the particles on human umbilical vein endothelial cells (HUVEC) was shown to be minimal. The ability of the polymeric contrast agent formulation to create contrast was similar to that of Gd-DTPA alone. These results demonstrate the possible utility of the contrast agent-loaded polymeric particles for plaque detection with MRI.

  16. MULTIFUNCTIONAL SYNTHETIC POLY(L-GLUTAMIC ACID)-BASED CANCER THERAPEUTIC AND IMAGING AGENTS

    PubMed Central

    Melancon, Marites P.

    2012-01-01

    Modern polymer chemistry has led to the generation of a number of biocompatible synthetic polymers have been increasingly studied as efficient carriers for drugs and imaging agents. Synthetic biocompatible polymers have been used to improve the efficacy of both small-molecular-weight therapeutics and imaging agents. Furthermore, multiple targeted anticancer agents and/or imaging reporters can be attached to a single polymer chain, allowing multifunctional and/or multimodality therapy and molecular imaging. Having both an anticancer drug and an imaging reporter in a single polymer chain allows noninvasive real-time visualization of the pharmacokinetics of polymeric drug delivery systems, which can uncover and explain the complicated mechanisms of in vivo drug delivery and their correlation to pharmacodynamics. This review examines use of the synthetic biocompatible polymer poly(L-glutamic acid) (PG) as an efficient carrier of cancer therapeutics and imaging agents. This review will summarize and update our recent research on use of PG as a platform for drug delivery and molecular imaging, including recent clinical findings with respect to PG-paclitaxel (PG-TXL); the combination of PG-TXL with radiotherapy; mechanisms of action of PG-TXL; and noninvasive visualization of in vivo delivery of polymeric conjugates with contrast-enhanced magnetic resonance imaging (MRI), optical imaging, and multimodality imaging. PMID:21303613

  17. Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid: a useful new agent to evaluate myocardial fatty acid uptake

    SciTech Connect

    Knapp, F.F. Jr.; Goodman, M.M.; Callahan, A.P.; Kirsch, G.

    1986-04-01

    Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) has been prepared as a new terminal iodophenyl-substituted fatty acid containing dimethyl-branching at the beta position. For the synthesis of this new agent, chain homologation was accomplished by fabrication of a 2,5-disubstituted thiophene by successive Friedel-Crafts acylation and Wolff-Kishner reduction reactions, followed by thiophene ring opening. The dimethyl-branching was introduced using the monomethyl ester of dimethylglutaryl chloride. Radioiodination of the 15-phenyl-3,3-dimethylpentadecanoic acid substrate in the para position then gave DMIPP. Iodine-125-labeled DMIPP showed rapid, high myocardial uptake (min, mean % injected dose/g) in fasted rats (5, 4.67; 30, 5.06; 60, 4.79; 120, 4.37), and also exhibited good heart:blood ratios (min, heart:blood: 5, 3:1; 30, 12:1; 60, 12:1; 120, 13:1). To further evaluate the effects of dimethyl-branching, the biodistribution properties of DMIPP were compared with the 3-monomethyl-branched (15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid; BMIPP) and the unbranched (15-(p-iodophenyl)pentadecanoic acid; IPP) analogs. A triple-labeled (/sup 123/I)DMIPP/(/sup 131/I)BMIPP/(/sup 125/I)IPP mixture was administered to groups of fasted rats. These results confirmed the greater myocardial retention and higher heart:blood ratios observed with DMIPP in comparison with both the 3-monomethyl-(BMIPP) and unbranched (IPP) analogs. These data suggest that (/sup 123/3I)DMIPP is an excellent candidate for clinical evaluation of regional energy substrates (fatty acid) uptake.

  18. Application of a new generation of complexing agents in removal of heavy metal ions from different wastes.

    PubMed

    Kołodyńska, Dorota

    2013-09-01

    Complexing agents are extensively applied in many fields of industry. They are used to provide effective controlling trace metal ions in cleaning industries, textile, pulp and paper production, water treatment, agriculture, food industries, etc. Recently, the low biodegradability of these ligands and their accumulation in the environment has become a cause for concern. Therefore, replacement of ethylenediaminetetraacetic acid and diethylenetriaminepentaacetic acid by more environmentally friendly chelating agents is highly desirable. So far, these acids and their salts have been applied as components of household chemistry, cosmetics, modern microelement fertilizers and agrochemicals. This paper reviews the sorption of heavy metal ions such as Cu(II), Zn(II), Cd(II) and Pb(II) in the presence of the above-mentioned complexing agents on commercially available anion exchangers of different matrix. The obtained sorption results were fitted using the Langmuir and Freundlich sorption isotherm models. The kinetic data were also analysed using the Lagergren, Ho and McKay sorption kinetic equations. The studies were carried out considering the effects of such important parameters as phase contact time, initial concentration, pH and temperature.

  19. Failure of various agents to decrease oleic acid pulmonary albumin leak.

    PubMed

    Sugerman, H J; Blocher, C R; Hirsch, J I; Strash, A M; Tatum, J L

    1983-05-01

    Computerized pulmonary gamma scintigraphy has been shown to be a sensitive technique for the measurement of albumin flux in oleic acid pulmonary microvascular injury. In this technique technetium-99m-tagged human serum albumin is administered intravenously and lung:heart radioactivity ratios are constructed. This ratio remains constant unless there is a net flux of albumin from the vascular space into the lung, when a rising ratio is seen, called the "slope of injury" or SI. Gamma scintigraphy provides a method to rapidly screen the ability of various possible therapeutic agents to reduce the flux of albumin in experimental ARDS. In this study, 0.05 ml/kg oleic acid produced a significant increase in the SI. None of the agents tested (30 mg/kg methylprednisolone, 12.5 mg/kg ibuprofen, 4 mg/kg MK-447, a superoxide radical scavenger, or 140 mg/kg calcium gluconate) were able to alter the scintigraphically measured increased albumin flux produced by 0.05 ml/kg oleic acid.

  20. Dual-modal MRI contrast agent with aggregation-induced emission characteristic for liver specific imaging with long circulation lifetime.

    PubMed

    Chen, Yilong; Li, Min; Hong, Yuning; Lam, Jacky W Y; Zheng, Qichang; Tang, Ben Zhong

    2014-07-09

    We herein report a novel dual-modal MRI contrast agent, TPE-2Gd, for both magnetic and fluorescence imaging. TPE-2Gd consists of a hydrophobic tetraphenylethene (TPE) fluorophore and two hydrophilic gadolinium (Gd) diethylenetriaminepentaacetic acid moieties. As an amphiphilic molecule, TPE-2Gd aggregates into micelles at a high concentration in aqueous medium. These aggregates are highly emissive, showing an aggregation-induced emission (AIE) characteristic. TPE-2Gd is used as a fluorescent agent for cell imaging, which demonstrates negligible cytotoxicity and excellent photostability owing to its AIE property. As a magnetic resonance imaging (MRI) contrast agent, TPE-2Gd exhibits similar longitudinal relaxivity in water (R1,TPE-2Gd = 3.36 ± 0.10 s(-1) per mM of Gd(3+)) as those commercial agents (e.g., Magnevist, R1,magnevist = 3.70 ± 0.02 s(-1) per mM of Gd(3+)). Compared with Magnevist, the circulation lifetime of TPE-2Gd nanoaggregates in living rats is extended from 10 min to 1 h. With relatively high specificity to the liver, the MR imaging could remain hyperintense in liver even after 150 min post injection. These TPE-2Gd nanoparticles can be excreted gradually via renal filtration due to the disassembly of the nanoparticles into small molecules during circulation. TPE-2Gd could thus potentially be used as a liver specific MRI contrast agent for clinical diagnosis.

  1. Evaluation of unnatural cyclic amino acids as boron delivery agents for treatment of melanomas and gliomas.

    PubMed

    Barth, Rolf F; Kabalka, George W; Yang, Weilian; Huo, Tianyao; Nakkula, Robin J; Shaikh, Aarif L; Haider, Syed A; Chandra, Subhash

    2014-06-01

    Unnatural cyclic amino acids (UNAAs) are a new class of boron delivery agents that are in a pre-clinical stage of evaluation. In the present study, the biodistribution of racemic forms of the cis- and trans-isomers of the boronated UNAA 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC) and 1-amino-3-boronocycloheptanecarboxylic acid (ABCHC) were evaluted in B16 melanoma bearing mice and this was compared to l-p-boronophenylalanine (BPA). Boron concentrations were determined by inductively coupled plasma-optical emission spectroscopy (ICP-OES) at 2.5h following intraperitoneal (i.p.) injection of the test agents at a concentration equivalent to 24mg/B/kg. While all compounds attained comparable tumor boron concentrations, the tumor/blood (T/Bl) boron concentration ratios were far superior for both cis-ABCPC and cis-ABCHC compared to BPA (T/Bl=16.4, and 15.1 vs. 5.4). Secondary ion mass spectrometry (SIMS) imaging revealed that the cis-ABCPC delivered boron to the nuclei, as well as the cytoplasm of B16 cells. Next, a biodistribution study of cis-ABCPC and BPA was carried out in F98 glioma bearing rats following i.p. administration. Both compounds attained comparable tumor boron concentrations but the tumor/brain (T/Br) boron ratio was superior for cis-ABCPC compared to BPA (6 vs. 3.3). Since UNAAs are water soluble and cannot be metabolized by tumor cells, they could be potentially more effective boron delivery agents than BPA. Our data suggest that further studies are warranted to evaluate these compounds prior to the initiation of clinical studies.

  2. Synthesis and biological evaluation of pseudolaric acid B derivatives as potential immunosuppressive agents.

    PubMed

    Chen, Shou-Qiang; Wang, Jie; Zhao, Chuan; Sun, Qiang-Wen; Wang, Yi-Teng; Ai, Ting; Li, Tan; Gao, Ying; Wang, Huo; Chen, Hong

    2015-01-01

    Pseudolaric acid B (PB) derivatives with immunosuppressive activity were found by our group. In order to find potential immunosuppressive agents with high efficacy and low toxicity, a series of novel PB derivatives were synthesized and evaluated on their immunosuppressive activities. Most of the synthesized compounds were tested in vitro on murine T and B proliferation. In particular, compound 11 exhibited excellent inhibitory activity toward murine T cells (up to 19-fold enhancement compared to that of mycophenolatemofetil) and little cytotoxicity toward normal murine spleen cells. These experimental data demonstrated that some of these PB derivatives have great potential for future immunosuppressive studies.

  3. In vivo efficacy of the diuretic agent ethacrynic acid against multiple myeloma.

    PubMed

    Kim, Young; Gast, Sanna-Marie; Endo, Tomoyuki; Lu, Desheng; Carson, Dennis; Schmidt-Wolf, Ingo G H

    2012-05-01

    It was recently confirmed that the diuretic agent ethacrynic acid (EA) inhibits Wnt/beta catenin signaling in myeloma. This study investigated the antitumor effect of EA in vivo in a murine myeloma model. In vivo, tumor growth was significantly reduced and overall survival significantly prolonged in mice treated with EA as compared to untreated mice. Interestingly, this effect was higher as compared to the effect by lenalidomide, a commonly used drug against myeloma. These results reveal a significant in vivo effect by EA against myeloma.

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

    PubMed Central

    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

  5. Conversion of glucose to fatty acids and methane: roles of two mycoplasmal agents

    SciTech Connect

    Rose, C.S.; Pirt, S.J.

    1981-07-01

    Two species of obligately anaerobic mycoplasmas were the major components of a methanogenic glucose-limited enrichment culture. In pure culture, one of these organisms, tentatively named Anaeroplasma sp. strain London, was shown to be responsible for the fermentation of glucose to fatty acids, hydrogen, and carbon dioxide; the other mycoplasma was shown to produce methane from hydrogen and carbon dioxide and was named Methanoplasma elizabethii. This same methanogenic mycoplasma contained a low-molecular-weight fluorescent cofactor which had a maximum light absorbance at 430 nm. When both species of mycoplasmas were grown together on glucose, fermentation products included fatty acids and methane. For the first time, mycoplasmas are implicated as agents of anaerobic degradation and methanogenesis in a sewage sludge digester.

  6. Lignosulfonates carboxylated with chloroacetic acid as additives in oil recovery processes involving chemical recovery agents

    SciTech Connect

    Kalfoglou, G.

    1981-05-19

    A process for producing petroleum from subterranean formations is disclosed wherein production from the formation is obtained by driving a fluid from an injection well to a production well. The process involves injecting via the injection well into the formation an aqueous solution of lignosulfonates carboxylated with chloroacetic acid as a sacrificial agent to inhibit the deposition of surfactant and/or polymer on the reservoir matrix. The process may best be carried out by injecting the lignosulfonates carboxylated with chloroacetic acid into the formation through the injection well mixed with either a polymer, a surfactant solution and/or a micellar dispersion. This mixture would then be followed by a drive fluid such as water to push the chemicals to the production well.

  7. Antimicrobial peptides incorporating non-natural amino acids as agents for plant protection.

    PubMed

    Ng-Choi, Iteng; Soler, Marta; Güell, Imma; Badosa, Esther; Cabrefiga, Jordi; Bardaji, Eduard; Montesinos, Emilio; Planas, Marta; Feliu, Lidia

    2014-04-01

    The control of plant pathogens is mainly based on copper compounds and antibiotics. However, the use of these compounds has some limitations. They have a high environmental impact and the use of antibiotics is not allowed in several countries. Moreover, resistance has been developed to these pathogens. The identification of new agents able to fight plant pathogenic bacteria and fungi will represent an alternative to currently used antibiotics or pesticides. Antimicrobial peptides are widely recognized as promising candidates, however naturally occurring sequences present drawbacks that limit their development. These include susceptibility to protease degradation and low bioavailability. To overcome these problems, research has focused on the introduction of unnatural amino acids into lead peptide sequences. In particular, we have improved the biological profile of antimicrobial peptides active against plant pathogenic bacteria and fungi by incorporating triazolyl, biaryl and D-amino acids into their sequence. These modifications and their influence on the biological activity are summarized.

  8. Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats.

    PubMed

    Fan, Hua-Ying; Yang, Ming-Yan; Qi, Dong; Zhang, Zuo-Kai; Zhu, Lin; Shang-Guan, Xiu-Xin; Liu, Ke; Xu, Hui; Che, Xin

    2015-07-21

    Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS.

  9. Salvianolic acid A as a multifunctional agent ameliorates doxorubicin-induced nephropathy in rats

    PubMed Central

    Fan, Hua-Ying; Yang, Ming-Yan; Qi, Dong; Zhang, Zuo-Kai; Zhu, Lin; Shang-Guan, Xiu-Xin; Liu, Ke; Xu, Hui; Che, Xin

    2015-01-01

    Nephrotic syndrome (NS) is still a therapeutic challenge. To date there is no ideal treatment. Evidence suggest that multidrug therapy has more effect than monotherapy in amelioration of renal injury. Salvianolic acid A (SAA) is the major active component of Salviae Miltiorrhizae Bunge. Previous studies have demonstrated that SAA is a multi-target agent and has various pharmacological activities. The pleiotropic properties of SAA predict its potential in the treatment of NS. The study investigated the effect of SAA on doxorubicin-induced nephropathy. The kidney function related-biochemical changes, hemorheological parameters and oxidative stress status were determined, and histological examination using light and transmission electron microcopies and western blot analysis were also performed. Results revealed that treatment with SAA alleviated histological damages, relieved proteinuria, hypoalbuminemia and hyperlipidemia, reduced oxidative stress, as well as improving hemorheology. Furthermore, SAA restored podocin expression, down-regulated the expression of NF-κB p65 and p-IκBα while up-regulating IκBα protein expression. Overall, as a multifunctional agent, SAA has a favorable renoprotection in doxorubicin-induced nephropathy. The anti-inflammation, antioxidant, amelioration of podocyte injury, improvement of hemorheology and hypolipidemic properties may constituent an important part of its therapeutic effects. All these indicate that SAA is likely to be a promising agent for NS. PMID:26194431

  10. Hyaluronic acid and its use as a "rejuvenation" agent in cosmetic dermatology.

    PubMed

    Andre, Pierre

    2004-12-01

    Since 1996, hyaluronic acid (HA) has been launched onto the market in Europe. Since then, different companies proposed their HAs. Biomatrix (NJ, USA) proposes an animal-derived HA (from rooster comb). Q-Med AB (Uppsala, Sweden) and LEA-DERM (Paris, France) are the main companies to have a nonanimal HA. HA is produced by bacterial fermentation from a specific strain of streptococci. HA has no species specificity and theoretically has no risk of allergy. No skin testing is necessary before injecting because HA is a biodegradable agent. To be utilized as a filler agent for improving wrinkles, scars, or increasing volumes, HA must be stabilized to obtain a sufficient half-life. Process of stabilization varies, according to each manufacturer. This explains the differences in longevity and in viscosity of the different products. Several HAs are suitable to fine lines, to deep wrinkles/folds, or to increase volume. A new indication for "rejuvenation" is injection into the superficial dermis and epidermis. The HA (stabilized or not) is not used to fill in but rather to hydrate and finally to rejuvenate the skin. This procedure must be repeated at intervals of a few weeks or months. If HA is the safest filler agent in cosmetic indications today, some rare side effects may appear and must be known to inform patients. Most of these complications are not severe and will disappear when the product is degraded.

  11. Hyaluronic acid as an internal wetting agent in model DMAA/TRIS contact lenses.

    PubMed

    Weeks, Andrea; Luensmann, Doerte; Boone, Adrienne; Jones, Lyndon; Sheardown, Heather

    2012-11-01

    Model silicone hydrogel contact lenses, comprised of N,N-dimethylacrylamide and methacryloxypropyltris (trimethylsiloxy) silane, were fabricated and hyaluronic acid (HA) was incorporated as an internal wetting agent using a dendrimer-based method. HA and dendrimers were loaded into the silicone hydrogels and cross-linked using 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide chemistry. The presence and location of HA in the hydrogels was confirmed using X-ray photoelectron spectroscopy and confocal laser scanning microscopy, respectively. The effects of the presence of HA on the silicone hydrogels on hydrophilicity, swelling behavior, transparency, and lysozyme sorption and denaturation were evaluated. The results showed that HA increased the hydrophilicity and the equilibrium water content of the hydrogels without affecting transparency. HA also significantly decreased the amount of lysozyme sorption (p < 0.002). HA had no effect on lysozyme denaturation in hydrogels containing 0% and 1.7% methacrylic acid (MAA) (by weight) but when the amount of MAA was increased to 5%, the level of lysozyme denaturation was significantly lower compared to control materials. These results suggest that HA has great potential to be used as a wetting agent in silicone hydrogel contact lenses to improve wettability and to decrease lysozyme sorption and denaturation.

  12. Nitrilase-catalyzed production of pyrazinoic acid, an antimycobacterial agent, from cyanopyrazine by resting cells of Rhodococcus rhodochrous J1.

    PubMed

    Kobayashi, M; Yanaka, N; Nagasawa, T; Yamada, H

    1990-10-01

    Using resting cells of Rhodococcus rhodochrous J1, in which a large amount of nitrilase is induced, a simple and efficient bioconversion process for the production of pyrazinoic acid, an antimycobacterial agent, through catalysis by a nitrilase was developed. The reaction conditions for production of pyrazinoic acid were optimized. Under optimum conditions, 3.5 M cyanopyrazine was converted to pyrazinoic acid, with a molar conversion yield of 100%. The highest yield achieved corresponded to 434 g of pyrazinoic acid per liter of reaction mixture. The synthesized pyrazinoic acid was isolated and identified physico-chemically.

  13. Anthranilic acid analogs as diamagnetic CEST MRI contrast agents that feature an intramolecular-bond shifted hydrogen.

    PubMed

    Song, Xiaolei; Yang, Xing; Ray Banerjee, Sangeeta; Pomper, Martin G; McMahon, Michael T

    2015-01-01

    Diamagnetic chemical exchange saturation transfer (diaCEST) agents are a new class of imaging agents, which have unique magnetic resonance (MR) properties similar to agents used for optical imaging. Here we present a series of anthranilic acid analogs as examples of diaCEST agents that feature an exchangeable proton shifted downfield, namely, an intramolecular-bond shifted hydrogen (IM-SHY), which produces significant and tunable contrast at frequencies of 4.8-9.3 ppm from water. Five analogs of N-sulfonyl anthranilic acids are all highly soluble and produced similar CEST contrast at ~6-8 ppm. We also discovered that flufenamic acid, a commercial nonsteroidal anti-inflammatory drug, displayed CEST contrast at 4.8 ppm. For these N-H IM-SHY agents, the contrast produced was insensitive to pH, making them complementary to existing diaCEST probes. This initial IM-SHY library includes the largest reported shifts for N-H protons on small organic diaCEST agents, and should find use as multifrequency MR agents for in vivo applications.

  14. Natural fatty acid synthase inhibitors as potent therapeutic agents for cancers: A review.

    PubMed

    Zhang, Jia-Sui; Lei, Jie-Ping; Wei, Guo-Qing; Chen, Hui; Ma, Chao-Ying; Jiang, He-Zhong

    2016-09-01

    Context Fatty acid synthase (FAS) is the only mammalian enzyme to catalyse the synthesis of fatty acid. The expression level of FAS is related to cancer progression, aggressiveness and metastasis. In recent years, research on natural FAS inhibitors with significant bioactivities and low side effects has increasingly become a new trend. Herein, we present recent research progress on natural fatty acid synthase inhibitors as potent therapeutic agents. Objective This paper is a mini overview of the typical natural FAS inhibitors and their possible mechanism of action in the past 10 years (2004-2014). Method The information was collected and compiled through major databases including Web of Science, PubMed, and CNKI. Results Many natural products induce cancer cells apoptosis by inhibiting FAS expression, with fewer side effects than synthetic inhibitors. Conclusion Natural FAS inhibitors are widely distributed in plants (especially in herbs and foods). Some natural products (mainly phenolics) possessing potent biological activities and stable structures are available as lead compounds to synthesise promising FAS inhibitors.

  15. Facile synthesis of graphene from graphite using ascorbic acid as reducing agent

    NASA Astrophysics Data System (ADS)

    Andrijanto, Eko; Shoelarta, Shoerya; Subiyanto, Gatot; Rifki, Sadur

    2016-04-01

    Graphene has attracted a tremendous attention in recent years due to its unique properties such as mechanical, thermal, optical and electrical properties. However, a large scale production of this material is still an issue and subjected to intense research efforts. Here, we show a simple and green approach of the graphene synthesis from graphene oxide using ascorbic acid as reduction agent. A facile synthesis of graphene (rGO) through chemical oxidation of graphite into graphene oxide (GO) was described using modified Hummers method (Improved Tour Method/ITM). The ITM method does not produce toxic gas and the temperature of the oxidation is easily controlled using ice bath. The synthesized of graphene oxide was highly soluble and stable in water. The reduction of graphene oxide into graphene was performed using ascorbic acid (AA) in mild condition. The combined ITM method and green reduction using ascorbic acid open the avenue of replacing hydrazine in the reduction of graphite oxide into graphene and may be very important step for bulk production of graphene.

  16. Targeted delivery of 5-fluorouracil to cholangiocarcinoma cells using folic acid as a targeting agent.

    PubMed

    Ngernyuang, Nipaporn; Seubwai, Wunchana; Daduang, Sakda; Boonsiri, Patcharee; Limpaiboon, Temduang; Daduang, Jureerut

    2016-03-01

    There are limits to the standard treatment for cholangiocarcinoma (CCA) including drug resistance and side effects. The objective of this study was to develop a new technique for carrying drugs by conjugation with gold nanoparticles and using folic acid as a targeting agent in order to increase drug sensitivity. Gold nanoparticles (AuNPs) were functionalized with 5-fluorouracil (5FU) and folic acid (FA) using polyethylene glycol (PEG) shell as a linker (AuNPs-PEG-5FU-FA). Its cytotoxicity was tested in CCA cell lines (M139 and M213) which express folic acid receptor (FA receptor). The results showed that AuNPs-PEG-5FU-FA increased the cytotoxic effects in the M139 and M213 cells by 4.76% and 7.95%, respectively compared to those treated with free 5FU+FA. It is found that the cytotoxicity of the AuNPs-PEG-5FU-FA correlates with FA receptor expression suggested the use of FA as a targeted therapy. The mechanism of cytotoxicity was mediated via mitochondrial apoptotic pathway as determined by apoptosis array. In conclusion, our findings shed some light on the use of gold nanoparticles for conjugation with potential compounds and FA as targeted therapy which contribute to the improvement of anti-cancer drug efficacy. In vivo study should be warranted for its effectiveness of stability, biosafety and side effect reduction.

  17. Crystal growth of aragonite and calcite in presence of citric acid, DTPA, EDTA and pyromellitic acid.

    PubMed

    Westin, K-J; Rasmuson, A C

    2005-02-15

    The influence of four calcium complexing substances, i.e., citric acid (CIT), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA) and pyromellitic acid (PMA), on the crystal growth rate of the calcium carbonate polymorphs aragonite and calcite has been studied. Using a seeded constant supersaturation method supersaturation was maintained at 4 by keeping a constant pH of 8.5 through addition of sodium carbonate and calcium chloride solutions. The unique composition of each solution was calculated using chemical speciation. The growth rate was interpreted in terms of an overall growth rate. For both calcite and aragonite, the crystal growth rate is significantly reduced in the presence of the calcium complexing substances. The growth retarding effect depends on both the concentration and the polymorph. The relative crystal growth rate was correlated to the total complexing agent concentration using a Langmuir adsorption approach. Aragonite appeared fully covered for lower total concentrations than calcite. Furthermore, CIT very efficiently blocked aragonite growth contrary to what was observed for calcite. This is thought to be related to certain distinct features of the dominant aragonite crystal faces compared to the dominant calcite faces.

  18. Evolution in Medicinal Chemistry of Ursolic Acid Derivatives as Anticancer Agents

    PubMed Central

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-01-01

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA. PMID:25617694

  19. Evolution in medicinal chemistry of ursolic acid derivatives as anticancer agents.

    PubMed

    Chen, Haijun; Gao, Yu; Wang, Ailan; Zhou, Xiaobin; Zheng, Yunquan; Zhou, Jia

    2015-03-06

    Currently, there is a renewed interest in common dietaries and plant-based traditional medicines for the prevention and treatment of cancer. In the search for potential anticancer agents from natural sources, ursolic acid (UA), a pentacyclic triterpenoid widely found in various medicinal herbs and fruits, exhibits powerful biological effects including its attractive anticancer activity against various types of cancer cells. However, the limited solubility, rapid metabolism and poor bioavailability of UA restricted its further clinical applications. In the past decade, with substantial progress toward the development of new chemical entities for the treatment of cancer, numerous UA derivatives have been designed and prepared to overcome its disadvantages. Despite extensive effort, discovery of effective UA derivatives has so far met with only limited success. This review summarizes the current status of the structural diversity and evolution in medicinal chemistry of UA analogues and provides a detailed discussion of future direction for further research in the chemical modifications of UA.

  20. Effect of chaotropic agents on reversible unfolding of a soybean (Glycine max) seed acid phosphatase.

    PubMed

    Cavagis, Alexandre Donizeti Martins; Granjeiro, Paulo Afonso; Ferreira, Carmen Veríssima; Aoyama, Hiroshi

    2004-04-01

    In this work we examined the effect of urea and guanidinium chloride on the structural stability of a single isoform of soybean seed acid phosphatase, based on the intensity of tryptophan fluorescence as a function of denaturant concentration. The free energy of unfolding, DeltaGu, was calculated at 25 degrees C as a function of the concentrations of both chaotropic agents; the conformational stability, DeltaG (H2O), was determined to be 2.48 kcal mol(-1). Center of mass, determined from analysis of fluorescence data, was used as a parameter to assess conformational changes. Our results indicate that complete enzyme inactivation occurred before full enzyme unfolding in both cases, and suggest that there are differences between the conformational flexibility of the active-site and that of the macromolecule as a whole.

  1. Trapping of organophosphorus chemical nerve agents in water with amino acid functionalized baskets.

    PubMed

    Ruan, Yian; Dalkiliç, Erdin; Peterson, Paul W; Pandit, Aroh; Dastan, Arif; Brown, Jason D; Polen, Shane M; Hadad, Christopher M; Badjić, Jovica D

    2014-04-07

    We prepared eleven amino-acid functionalized baskets and used (1) H NMR spectroscopy to quantify their affinity for entrapping dimethyl methylphosphonate (DMMP, 118 Å(3) ) in aqueous phosphate buffer at pH=7.0±0.1; note that DMMP guest is akin in size to chemical nerve agent sarin (132 Å(3) ). The binding interaction (Ka ) was found to vary with the size of substituent groups at the basket's rim. In particular, the degree of branching at the first carbon of each substituent had the greatest effect on the host-guest interaction, as described with the Verloop's B1 steric parameter. The branching at the remote carbons, however, did not perturb the encapsulation, which is important for guiding the design of more effective hosts and catalysts in future.

  2. "On-off" thermoresponsive coating agent containing salicylic acid applied to maize seeds for chilling tolerance.

    PubMed

    Guan, Yajing; Li, Zhan; He, Fei; Huang, Yutao; Song, Wenjian; Hu, Jin

    2015-01-01

    Chilling stress is an important constraint for maize seed establishment in the field. In this study, a type of "on-off" thermoresponsive coating agent containing poly (N-isopropylacrylamide-co-butylmethacrylate) (Abbr. P(NIPAm-co-BMA)) hydrogel was developed to improve the chilling tolerance of coated maize seed. The P(NIPAm-co-BMA) hydrogel was synthesized by free-radical polymerization of N-isopropylacrylamide (NIPAm) and butylmethacrylate (BMA). Salicylic acid (SA) was loaded in the hydrogel as the chilling resistance agent. SA-loaded P(NIPAm-co-BMA) was used for seed film-coating of two maize varieties, Huang C (HC, chilling-tolerant) and Mo17 (chilling-sensitive), to investigate the coated seed germination and seedling growth status under chilling stress. The results showed that the hydrogel obtained a phase transition temperature near 12°C with a NIPAM to MBA weight ratio of 1: 0.1988 (w/w). The temperature of 12°C was considered the "on-off" temperature for chilling-resistant agent release; the SA was released from the hydrogel more rapidly at external temperatures below 12°C than above 12°C. In addition, when seedlings of both maize varieties suffered a short chilling stress (5°C), higher concentrations of SA-loaded hydrogel resulted in increased germination energy, germination percentage, germination index, root length, shoot height, dry weight of roots and shoots and protective enzyme activities and a decreased malondialdehyde content in coated maize seeds compared to single SA treatments. The majority of these physiological and biochemical parameters achieved significant levels compared with the control. Therefore, SA-loaded P(NIPAm-co-BMA), a nontoxic thermoresponsive hydrogel, can be used as an effective material for chilling tolerance in film-coated maize seeds.

  3. Material characterization of poly-lactic acid shelled ultrasound contrast agent and their dynamics

    NASA Astrophysics Data System (ADS)

    Paul, Shirshendu; Russakow, Daniel; Rodgers, Tyler; Sarkar, Kausik; Cochran, Michael; Wheatley, Margaret

    2011-11-01

    Micron-size gas bubbles encapsulated with lipids and proteins are used as contrast enhancing agents for ultrasound imaging. Biodegradable polymer poly-lactic acid (PLA) has recently been suggested as a possible means of encapsulation. Here, we report in vitro measurement of attenuation and scattering of ultrasound through an emulsion of PLA agent as well as theoretical modeling of the encapsulated bubble dynamics. The attenuation measured with three different transducers of central frequencies 2.25, 3.5 and 5 MHz, shows a peak around 2-3 MHz. These bubbles also show themselves to possess excellent scattering characteristics including strong non-linear response that can be used for harmonic and sub-harmonic contrast imaging. Our recently developed interfacial rheological models are applied to describe the dynamics of these bubbles; rheological model properties are estimated using measured attenuation data. The model is then applied to predict nonlinear scattered response, and the prediction is compared against experimental observation. Partially supported by NSF and NIH.

  4. Photochemical degradation of sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid in different water matrices.

    PubMed

    Ji, Yuefei; Zhou, Lei; Zhang, Ya; Ferronato, Corinne; Brigante, Marcello; Mailhot, Gilles; Yang, Xi; Chovelon, Jean-Marc

    2013-10-01

    The occurrence of sunscreen agents in natural environment is of scientific concern recently due to their potential risk to ecology system and human beings as endocrine disrupting chemicals (EDCs). In this work the photodegradation mechanism and pathways of sunscreen agent 2-phenylbenzimidazole-5-sulfonic acid (PBSA) were investigated under artificial solar irradiation with the goal of assessing the potential of photolysis as a transformation mechanism in aquatic environments. The quantum yield of PBSA direct photolysis in pH 6.8 buffer solution under filtered mercury lamp irradiation was determined as 2.70 × 10(-4). Laser flash photolysis (LFP) experiments confirmed the involvement of PBSA radical cation (PBSA(·+)) during direct photolysis. Acidic or basic condition facilitated PBSA direct photolysis in aqueous solution. Indirect photolysis out-competes direct photolysis as a major process for PBSA attenuation only at higher level of photosensitizers (e.g., NO3(-) > 2 mM). Thus, direct photolysis is likely to be the major loss pathway responsible for the elimination of PBSA in natural sunlit surface waters, while indirect photolysis (e.g., mediated by HO·) appeared to be less important due to a general low level of steady-state concentration of HO· ([HO·]ss) in natural surface waters. Direct photolysis pathways of PBSA includes desulfonation and benzimidazole ring cleavage, which are probably initiated by the excited triplet state ((3)PBSA*) and radical cation (PBSA(·+)). Conversely, hydroxylation products of PBSA and 2-phenyl-1H-benzimidazole as well as their ring opening intermediates were found in nitrate-induced PBSA photolysis, suggesting the indirect photodegradation was primarily mediated by HO and followed a different mechanism.

  5. Application of Hydrogen Bond Acidic Polycarbosilane Polymers and Solid-Phase Microextraction for the Collection of Nerve Agent Simulant

    DTIC Science & Technology

    2006-01-01

    and analyzed on a GC/MS with a SPME injection port. 20 3. Methodolgy This chapter describes the methods used to answer the research questions...can be improved by using a SPME polymer coating that is selective for nerve agents in place of current commercial polymers. This research focuses on...three hydrogen bond acidic polymers developed by the Naval Research Laboratory that have an increased affinity for nerve agents. These polymers

  6. Inactivation of Matrix-bound MMPs by Cross-linking Agents in Acid Etched Dentin

    PubMed Central

    Scheffel, Débora Lopes Salles; Hebling, Josimeri; Scheffel, Régis Henke; Agee, Kelly A.; Turco, Gianluca; de Souza Costa, Carlos Alberto; Pashley, David H.

    2014-01-01

    Objectives Published TEM analysis of in vivo resin-dentin bonds shows that in 44 months almost 70% of collagen fibrils from the hybrid layer disappear. Matrix metalloproteinases (MMPs) play an important role in that process and are thought to be the main factor responsible for the solubitization of dentin collagen. Therefore, this study aimed to evaluate the inactivation of matrix-bound MMPs by carbodiimide (EDC) or proanthocyanidin (PA) both cross-linking agents, or the MMP-inhibitor, chlorhexidine (CHX), on acid-etched dentin using a simplified MMP assay method. Methods Dentin beams (1×1×6mm) were obtained from mid-coronal dentin of sound third molars and randomly divided into 6 groups (G) according to the dentin treatment: G1: Deionized water (control), G2: 0.1M EDC, G3: 0.5M EDC, G4: 0.5M EDC+35% HEMA, G5: 5% Proanthocyanidin (PA) and G6: 2% CHX. The beams were etched for 15s with 37% phosphoric acid, rinsed and then immersed for 60s in one of the treatment solutions. The total MMP activity of dentin was analyzed for 1 h by colorimetric assay (Sensolyte). Data were submitted to Wilcoxon non-parametric test and Mann-Whitney tests (p>0.05). Results All experimental cross-linking solutions significantly reduced MMP activity compared to control, except 0.1M EDC (53.6% ±16.1). No difference was observed between cross-linking agents and 2% CHX 0.5M EDC + 35% HEMA (92.3% ±8.0) was similar to 0.5M EDC (89.1% ±6.4), 5% PA (100.8% ±10.9) and 2% CHX (83.4% ±10.9). Conclusion Dentin treatment with cross-linking agents is effective to significantly reduce MMP activity. Mixing 0.5M EDC and 35% HEMA did not influence EDC inhibitor potential. PMID:23786610

  7. Synthesis and biological evaluation of pyrazolylthiazole carboxylic acids as potent anti-inflammatory-antimicrobial agents.

    PubMed

    Khloya, Poonam; Kumar, Satish; Kaushik, Pawan; Surain, Parveen; Kaushik, Dhirender; Sharma, Pawan K

    2015-03-15

    Current Letter presents design, synthesis and biological evaluation of a novel series of pyrazolylthiazole carboxylates 1a-1p and corresponding acid derivatives 2a-2p. All 32 novel compounds were tested for their in vivo anti-inflammatory activity by carrageenan-induced rat paw edema method as well as for in vitro antimicrobial activity. All the tested compounds exhibited excellent AI activity profile. Three compounds 1p (R=Cl, R(1)=Cl), 2c (R=H, R(1)=F) and 2n (R=Cl, R(1)=OCH3) were identified as potent anti-inflammatory agents exhibiting edema inhibition of 93.06-89.59% which is comparable to the reference drug indomethacin (91.32%) after 3h of carrageenan injection while most of the other compounds displayed inhibition ⩾80%. In addition, pyrazolylthiazole carboxylic acids (2a-2p) also showed good antimicrobial profile. Compound 2h (R=OCH3, R(1)=Cl) showed excellent antimicrobial activity (MIC 6.25μg/mL) against both Gram positive bacteria comparable with the reference drug ciprofloxacin (MIC 6.25μg/mL).

  8. Dynamic wettability of wood surface modified by acidic dyestuff and fixing agent

    NASA Astrophysics Data System (ADS)

    Wei, Shuangying; Shi, Junyou; Gu, Jiyou; Wang, Di; Zhang, Yanhua

    2012-01-01

    Acidic dyestuffs can bring brilliant colors to the wood and fixing agents can avoid the color loss. They could change the surface wettability of wood, which impact the gluing process of veneers. In condition of the higher moisture content of wood, the rare veneers, the veneers dyed by acidic dyestuffs and the dyed veneers fixed by Chitosan were glued respectively by one-component wet-curing isocyanate adhesive and the contact angles (θ) of the different gluing interfaces were measured. The dynamic wettability of these gluing interfaces was characterized by both the contact angle θ and the spreading-penetration parameter (K) calculated by θ. The results showed that the θ-values decreased significantly with the extension of time and the initial contact angles (θi) decreased with the moisture contents of veneers increasing, but the variation of the balance contact angles (θe) was reversed with θi. When the moisture contents of veneers were same, the variation of θ of the rare veneers was minimal and the variation of θ of the fixed veneers was maximal. The K-values of these gluing interfaces all decreased significantly with the moisture contents of veneers increasing, but the variations of K were different. The wetting model describing the dynamic wetting process was established on the basis of these variations.

  9. Solubilizing properties of new surface-active agents, products of catalytic oxyethylation of cholic acid.

    PubMed

    Kołodziejczyk, Michał Krzysztof; Nachajski, Michal Jakub; Lukosek, Marek; Zgoda, Marian Mikołaj

    2013-01-01

    Solubilizing properties of aqueous solutions of a series of surface-active agents, products of oxyethylation of cholic acid, were examined in the present study. The content of oxyethylated segments determined by means of the 1H NMR method enabled the verification of the molecular mass of surfactants along with the calculation of the structural hydrophilic-lipophilic balance (HLB), the solubility parameter delta1/2, and the required solubility level of balance HLB(R). Viscosimetric measurements enabled the calculation of the limiting viscosity number, the content-average molecular mass, the effective volume, the hydrodynamic radius of the surfactant micelle and their equilibrium adducts with rutin, diclofenac and loratadine (BCS Class II and III). By means of the spectrophotometric method (UV) the amount of the solubilized diclofenac, loratadine and rutin (rutoside) was determined in the equilibrium system (saturated solution) in the environment of aqueous solutions of cholic acid derivatives of n(TE) = 20-70. The obtained results serve as a basis for determining the solubilization mechanism of lipophilic therapeutic products and indirectly for estimating the influence of the above process on pharmaceutical as well as biological availability of a micellar adduct from model drug forms (Lindbladt lithogenolitic index).

  10. Synthesis of Sugar-Boronic Acid Derivatives: A Class of Potential Agents for Boron Neutron Capture Therapy.

    PubMed

    Imperio, Daniela; Del Grosso, Erika; Fallarini, Silvia; Lombardi, Grazia; Panza, Luigi

    2017-04-07

    To date, sugar analogues that contain boronic acids as substitutes for hydroxyl groups are a class of compounds nearly unknown in the literature. The challenging synthesis of two sugar-boronic acid analogues is described, and data are retrieved on their solution behavior, stability, and toxicity. As these compounds were expected to mimic the behavior of carbohydrates, they were tested in regards to their future development as potential boron neutron capture therapy agents.

  11. Chelating agents used for plutonium and uranium removal in radiation emergency medicine.

    PubMed

    Fukuda, Satoshi

    2005-01-01

    The prospects of using chelating agents for increasing the excretion of actinides are reviewed. The removal of plutonium by chelating agents is of great importance because plutonium is extremely dangerous and induces cancer due to radiation toxicity. Similarly, uranium is a radionuclide, which causes severe renal dysfunction within a short time period due to chemical toxicity. It may also induce cancers such as leukemia and osteosarcoma in cases of long-term internal radiation exposure. Investigations on chelating agents for the removal of plutonium were initiated in the 1960's and 1970's. Diethylenetriaminepentaacetic acid (DTPA) is recognized as a chelating agent that accelerates the excretion of plutonium in early treatment after an accident. Thereafter, there has long been an interest in finding new chelating agents with radionuclide removal properties for use in therapy, and many chelating agents such as 3,4,3-LIHOPO and CBMIDA have been studied for their ability to remove plutonium and uranium. Recently, the focus has turned to drugs that have been used successfully in the treatment of a variety of other diseases, for example the iron chelating drug deferiprone or 1,2-dimethyl-3-hydroxypyrid-4-one (L1), which is used in thalassaemia and ethane-1-hydroxy-1,1-bisphosphonate (EHBP), which is used in osteoporosis. Within this context, it is important to examine the clinical use of these two drugs as well as the properties of the experimental chelators 3,4,3-LIHOPO and CBMIDA in order to identify possible uses in the treatment of radiation workers contaminated with plutonium and uranium.

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

    PubMed

    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.

  13. Dumb and dumber--the potential waste of a useful antistaphylococcal agent: emerging fusidic acid resistance in Staphylococcus aureus.

    PubMed

    Howden, Benjamin P; Grayson, M Lindsay

    2006-02-01

    Fusidic acid has activity against a range of pathogens but has mainly been used to treat staphylococcal infections. Fusidic acid monotherapy, especially topical preparations, has been strongly associated with the emergence of fusidic acid resistance among both methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-susceptible S. aureus. Key resistance determinants include mutations in the fusA gene, which encodes elongation factor G, and plasmid-mediated resistance (i.e., acquisition of resistance gene fusB). Clonal outbreaks of fusidic acid-resistant S. aureus have been noted throughout the United Kingdom and Europe, such that the efficacy of fusidic acid is threatened. Fusidic acid in combination with other agents, such as rifampicin, has proven effective for difficult-to-treat MRSA infections and provides a convenient oral alternative to oxazolidinones. Ensuring that systemic fusidic acid is always used in combination and that the use of topical fusidic acid is either abolished or restricted will be vital if we are to prevent the loss of this potentially useful agent.

  14. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer

    PubMed Central

    Vasudevan, Anita; Yu, Yingjie; Banerjee, Sanjeev; Woods, James; Farhana, Lulu; Rajendra, Sindhu G.; Patel, Aamil; Dyson, Gregory; Levi, Edi; Maddipati, Krishna Rao; Majumdar, Adhip P.N.; Nangia-Makker, Pratima

    2014-01-01

    Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer (CRC), are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSCs/CSLCs) underscoring the need for improved preventive and therapeutic strategies targeting CSCs/CSLCs. Omega-3 polyunsaturated fatty acids (ω-3 PUFA), have been reported to inhibit the growth of primary tumors, but their potential as a preventive agent for recurring cancers is un-explored. The primary objectives of this investigation are to examine whether eicosapentaenoic acid (EPA; one of the ω-3 PUFA) synergizes with FuOx (5-FU+Oxaliplatin), the backbone of colon cancer chemotherapy, and (b) whether EPA by itself or in combination with conventional chemotherapy prevents the recurrence of colon cancer via eliminating/suppressing CSCs/CSLCs. FuOx-resistant (chemo-resistant; CR) colon cancer cells, highly enriched in CSCs, were utilized for this study. While EPA alone was effective, combination of EPA and FuOx was more potent in (a) inhibiting cell growth, colonosphere formation and sphere-forming frequency, (b) increasing sphere disintegration, (c) suppressing the growth of SCID mice xenografts of CR colon cancer cells, and (d) decreasing pro-inflammatory metabolites in mice. Additionally, EPA + FuOx caused a reduction in CSC/CSLC population. The growth reduction by this regimen is the result of increased apoptosis as evidenced by PARP cleavage. Furthermore, increased pPTEN, decreased pAkt, normalization of β-catenin expression, localization and transcriptional activity by EPA suggests a role for PTEN/Akt axis and Wnt signaling in regulating this process. Our data suggest that EPA by itself or in combination with FuOx could be an effective preventive strategy for recurring CRC. PMID:25193342

  15. Omega-3 fatty acid is a potential preventive agent for recurrent colon cancer.

    PubMed

    Vasudevan, Anita; Yu, Yingjie; Banerjee, Sanjeev; Woods, James; Farhana, Lulu; Rajendra, Sindhu G; Patel, Aamil; Dyson, Gregory; Levi, Edi; Maddipati, Krishna Rao; Majumdar, Adhip P N; Nangia-Makker, Pratima

    2014-11-01

    Increasing evidence supports the contention that many malignancies, including sporadic colorectal cancer, are driven by the self-renewing, chemotherapy-resistant cancer stem/stem-like cells (CSC/CSLC), underscoring the need for improved preventive and therapeutic strategies targeting CSCs/CSLCs. Omega-3 polyunsaturated fatty acids (ω-3 PUFA), have been reported to inhibit the growth of primary tumors, but their potential as a preventive agent for recurring cancers is unexplored. The primary objectives of this investigation are (i) to examine whether eicosapentaenoic acid (EPA; one of the ω-3 PUFA) synergizes with FuOx (5-FU+Oxaliplatin), the backbone of colon cancer chemotherapy, and (ii) whether EPA by itself or in combination with conventional chemotherapy prevents the recurrence of colon cancer via eliminating/suppressing CSCs/CSLCs. FuOx-resistant (chemoresistant; CR) colon cancer cells, highly enriched in CSCs, were used for this study. Although EPA alone was effective, combination of EPA and FuOx was more potent in (i) inhibiting cell growth, colonosphere formation, and sphere-forming frequency, (ii) increasing sphere disintegration, (iii) suppressing the growth of SCID mice xenografts of CR colon cancer cells, and (iv) decreasing proinflammatory metabolites in mice. In addition, EPA + FuOx caused a reduction in CSC/CSLC population. The growth reduction by this regimen is the result of increased apoptosis as evidenced by PARP cleavage. Furthermore, increased pPTEN, decreased pAkt, normalization of β-catenin expression, localization, and transcriptional activity by EPA suggests a role for the PTEN-Akt axis and Wnt signaling in regulating this process. Our data suggest that EPA by itself or in combination with FuOx could be an effective preventive strategy for recurring colorectal cancer.

  16. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents.

    SciTech Connect

    Chen, Baowei; Shah, Saumil S.; Shin, Yongsoon; Lei, Chenghong; Liu, Jun

    2011-10-02

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterward can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in a pH 9.0 NaHCO(3)-Na(2)CO(3) buffer system and a gradual release in pH 7.4 simulated body fluid. The binding of OPAA to NH(2)-FMS can result in less tyrosinyl and tryptophanyl exposure OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme maintained the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as a medical countermeasure against the organophosphorus nerve agents.

  17. In vitro release of organophosphorus acid anhydrolase from functionalized mesoporous silica against nerve agents

    PubMed Central

    Chen, Baowei; Shah, Saumil S.; Shin, Yongsoon; Lei, Chenghong; Liu, Jun

    2011-01-01

    We report here that under different physiological conditions, biomolecular drugs can be stockpiled in a nanoporous support and afterwards can be instantly released when needed for acute responses, and the biomolecular drug molecules can also be gradually released from the nanoporous support over a long time for a complete recovery. Organophosphorus acid anhydrolase (OPAA) was spontaneously and largely entrapped in functionalized mesoporous silica (FMS) due to the dominant electrostatic interaction. The OPAA-FMS composite exhibited a burst release in pH 9.0, NaHCO3-Na2CO3 buffer system and a gradual release in pH 7.4, simulated body fluid. The binding of OPAA to NH2-FMS can result in less Trp exposure of OPAA molecules to aqueous environment. The bound OPAA in FMS displayed lower activity than the free OPAA in solution prior to the enzyme entrapment. However, the released enzyme still displayed the native conformational structure and the same high enzymatic activity as that prior to the enzyme entrapment. The in vitro results in the rabbit serum demonstrate that both OPAA-FMS and the released OPAA may be used as the medical measures against the organophosphorus nerve agents. PMID:22019765

  18. The uncoupling agent 2,4-dinitrophenol improves mitochondrial homeostasis following striatal quinolinic acid injections.

    PubMed

    Korde, Amit S; Sullivan, Patrick G; Maragos, William F

    2005-10-01

    It is now generally accepted that excitotoxic cell death involves bioenergetic failure resulting from the cycling of Ca2+ and the generation of reactive oxygen species (ROS) by mitochondria. Both Ca2+ cycling and ROS formation by mitochondria are dependent on the mitochondrial membrane potential (Deltapsi(m)) that results from the proton gradient that is generated across the inner membrane. Mitochondrial uncoupling refers to a condition in which protons cross the inner membrane back into the matrix while bypassing the ATP synthase. As a consequence of this "short-circuit," there is a reduction in Deltapsi(m). We have previously demonstrated that animals treated with the classic uncoupling agent 2,4-dinitrophenol (DNP) show significant protection against brain damage following striatal injections of the NMDA agonist quinolinic acid (QA). In an effort to elucidate the mechanism of neuroprotection, we have assessed the effects of DNP on several parameters of mitochondrial function caused by QA. The results presented herein demonstrate that treatment with DNP attenuates QA-induced increases in mitochondrial Ca2+ levels and ROS formation and also improves mitochondrial respiration. Our findings indicate that DNP may confer protection against acute brain injury involving excitotoxic pathways by mechanisms that maintain mitochondrial function.

  19. Competitive FRET-aptamer-based detection of methylphosphonic acid, a common nerve agent metabolite.

    PubMed

    Bruno, John G; Carrillo, Maria P; Phillips, Taylor; Vail, Neal K; Hanson, Douglas

    2008-09-01

    Competitive fluorescence resonance energy transfer (FRET)-aptamer-based assay formats are described for one-step detection of methylphosphonic acid (MPA; a metabolite of several organophosphorus (OP) nerve agents). AminoMPA was attached to tosyl-magnetic beads and used for DNA aptamer selection from which one dominant aptamer sequence emerged. Two different FRET approaches were attempted. In one approach, the complementary DNA sequence was used as a template for labeling the aptamer with Alexa Fluor 546 (AF 546)-14-dUTP by asymmetric PCR. Following 3-dimensional (3-D), molecular modeling of the aptamer-MPA complex, a series of three fluoresceinated aptamers labeled at positions 50, 51, and 52 in the putative optimal binding pocket were synthesized. In both FRET formats, aminoMPA was linked to Black Hole Quencher (BHQ-1 or BHQ-2)-succinimides and allowed to bind the fluorescein or AF 546-labeled MPA aptamer. Following gel filtration to purify the labeled MPA aptamer-BHQ-aminoMPA FRET complexes, the complexes were competed against various concentrations of unlabeled MPA, MPA derivatives, and unrelated compounds in titration and cross-reactivity studies. Both approaches yielded low microgram per milliliter detection limits for MPA with generally low levels of cross-reactivity for unrelated compounds. However, the data suggest a pattern of traits that may effect the direction (lights on or off) and intensity of the FRET.

  20. Can we consider zoledronic acid a new antitumor agent? Recent evidence in clinical setting.

    PubMed

    Santini, Daniele; Virzi, Vladimir; Fratto, Maria Elisabetta; Bertoldo, Francesco; Sabbatini, Roberto; Berardi, Rossana; Calipari, Nicola; Ottaviani, Davide; Ibrahim, Toni

    2010-02-01

    New emerging data suggest that bisphosphonates may exert antitumor properties. Preclinical studies have demonstrated that zoledronic acid (ZA) can induce direct and indirect antitumor activities such as inhibition of angiogenesis, invasion and adhesion of tumor cells, and overall tumor progression, stimulation of adoptive and innate immunity and emerging evidence suggests that the use of these agents may prevent the development of skeletal and extra skeletal metastases. This review will critically describe the new growing evidence of antitumor activity exerted by bisphosphonates in cancer patients, both in metastatic disease and in the adjuvant setting. The effects of bisphosphonates on survival in metastatic cancer patients will be described and evidence from retrospective analyses and prospective studies will be critically reported. The early evidence from prospective analyses of survival impact by ZA in the adjuvant setting in breast cancer will be discussed together with the recently published results of the ABCSG-12 study. A new "era" for bisphosphonates in the oncological setting is opening. The clinical data that will be reported in this review represent the first step in a path that will conduct us to explore new horizons in the field of adjuvant and metastatic cancer therapies.

  1. Cell morphology of extrusion foamed poly(lactic acid) using endothermic chemical foaming agent.

    PubMed

    Matuana, Laurent M; Faruk, Omar; Diaz, Carlos A

    2009-12-01

    Poly(lactic acid) (PLA) was foamed with an endothermic chemical foaming agent (CFA) through an extrusion process. The effects of polymer melt flow index, CFA content, and processing speed on the cellular structures, void fraction, and cell-population density of foamed PLA were investigated. The apparent melt viscosity of PLA was measured to understand the effect of melt index on the cell morphology of foamed PLA samples. The void fraction was strongly dependent on the PLA melt index. It increased with increasing melt index, reaching a maximum value, after which it decreased. Melt index showed no significant effect on the cell-population density of foamed samples within the narrow range studied. A gas containment limit was observed in PLA foamed with CFA. Both the void fraction and cell-population density increased with an initial increase in CFA content, reached a maximum value, and then decreased as CFA content continued to increase. The processing speed also affected the morphology of PLA foams. The void fraction reached a maximum value as the extruder's screw speed increased to 40 rpm and a further increase in the processing speed tended to reduce the void fraction of foamed samples. By contrast, cell-population density increased one order of magnitude by increasing the screw speed from 20 to 120 rpm. The experimental results indicate that a homogeneous and finer cellular morphology could be successfully achieved in PLA foamed in an extrusion process with a proper combination of polymer melt flow index, CFA content, and processing speed.

  2. Salvianolic Acid B, a Potential Chemopreventive Agent, for Head and Neck Squamous Cell Cancer

    PubMed Central

    Zhao, Yuan; Guo, Yinhan; Gu, Xinbin

    2011-01-01

    Head and neck squamous cell cancer (HNSCC) is one of the top ten cancers in the United States. The survival rate of HNSCC has only marginally improved over the last two decades. In addition, African-American men bear a disproportionate burden of this preventable disease. Therefore, a critical challenge of preventive health approaches is warranted. Salvianolic acid B (Sal-B) isolated from Salvia miltiorrhiza Bge, which is a well-know Chinese medicines has been safely used to treat and prevent aging diseases for thousand of years. Recently, the anticancer properties of Sal-B have received more attention. Sal-B significantly inhibits or delays the growth of HNSCC in both cultured HNSCC cells and HNSCC xenograft animal models. The following anticancer mechanisms have been proposed: the inhibition of COX-2/PGE-2 pathway, the promotion of apoptosis, and the modulation of angiogenesis. In conclusion, Sal-B is a potential HNSCC chemopreventive agent working through antioxidation and anti-inflammation mechanisms. PMID:21209716

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

    PubMed Central

    Hou, Lin; Zhang, Huijuan; Wang, Yating; Wang, Lili; Yang, Xiaomin; Zhang, Zhenzhong

    2015-01-01

    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. PMID:26213465

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

    PubMed

    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.

  5. [Effects of peeling agents (resorcinol, crystalline sulfur, salicylic acid) on the epidermis of guinea pig (author's transl)].

    PubMed

    Windhager, K; Plewig, G

    1977-08-22

    The mode of action of "classical peeling agents" such as resorcinol, crystalline sulfur, and salicylic acid on the epidermis is almost unknown. There are only a few experimental data available. Therefore the effects of resorcinol, crystalline sulfur, and salicylic acid were studied. A 1% and 3% concentration of these chemicals in vaselinum flavum or Unguentum Cordes was applied to the ears and flanks of adult male guinea pigs up to 14 days. Prior to biopsies at various time intervals, 3H-thymidine was injected intradermally. Specimens were paraffin embedded and routinely processed for autoradiographical analysis. The following parameters were assessed: Labelling index (L.I. in %); number of labelled basal cells per unit length of basement membrane; papillomatosis-index; and acanthosis-factor (projection histoplanimetry). The data were statistically analysed. The peeling agents induced a concentration-dependent increase of the L.I., acanthosis, and papillomatosis. Crystalline sulfur caused the most pronounced effect, followed by resorcinol. In contrast salicylic acid caused only a minute acanthosis factor and a slight increase in labelling. The correlation coefficient r of epidermal thickness to the L.I. for all concentrations and peeling agents used reaches the high figure of 0.978 for the ear. The 1% and 3% salicylic acid has a lower acanthosis factor than vaselinum flavum by itself. Preliminary autoradiographical studies in humans with 1% and 10% salicylic acid confirm these data. Salicylic acid counteracts acanthosis. These experiments show that crystalline sulfur and resorcinol have a potent effect on cell proliferation and acanthosis. They peel via proliferation hyperkeratosis. The mode of peeling by salicylic acid must be different, as cell proliferation and acanthosis are barely enhanced. The clinically known "keratolytic" effect of salicylic acid may be due to a direct action on the intercellular cement substance of the horny cells.

  6. Increase in the ozone decay time in acidic ozone water and its effects on sterilization of biological warfare agents.

    PubMed

    Uhm, Han S; Hong, Yi F; Lee, Han Y; Park, Yun H

    2009-09-15

    The sterilization properties of ozone in acidic water are investigated in this study. Acidification of water increases the ozone decay time by several times compared to the decay time in neutral water, thereby enhancing the sterilization strength of ozone in acidic water. A simple analytical model involving the viable microbial counts after contact with acidic ozone water was derived, and a sterilization experiment was conducted on bacterial cells using the acidic ozone water. The acidic ozone water was found to kill very effectively endospores of Bacillus atrophaeus ATCC 9372, thereby demonstrating the potential for disinfection of a large surface area in a very short time and for reinstating the contaminated environment as free from toxic biological agents.

  7. Evaluation of the therapeutic effect of percutaneous nephroureterolithotomy by Tc-99m diethylenetiaminepentaacetic acid (DTPA) renal scintigraphy--alteration of the renal fraction of blood flow, split-GFR, and renal mean transit time.

    PubMed

    Ishibashi, M; Morita, S; Rabito, C A; Umezaki, N; Matsuoka, K; Noda, S; Eto, K; Ohtake, H

    1990-01-01

    To evaluate the therapeutic effects of percutaneous nephroureterolithotomy, the renal function of eleven patients with renal calculi was studied, pre- and post-intervention. Renal function was determined, by renal scintigraphy with the renal agent, Tc-99m diethylenetriaminepentaacetic acid (DTPA). In each renal scintigram the renogram curve was analyzed and the following were determined by deconvolution analysis; the renal fraction of blood flow (RFBF), DTPA-glomerular filtration ratio (GFR), and the renal mean transit time (MTT). The successful results in percutaneous nephroureterolithotomy (PNL) was proven using the radionuclide technique in most cases. From these results it can be concluded that renal scintigraphy is an effective procedure to evaluate the effect of PNL for treating renal calculi and secondary hydronephrosis.

  8. Caffeic acid: potential applications in nanotechnology as a green reducing agent for sustainable synthesis of gold nanoparticles.

    PubMed

    Seo, Yu Seon; Cha, Song-Hyun; Yoon, Hye-Ran; Kang, Young-Hwa; Park, Youmie

    2015-04-01

    The sustainable synthesis of gold nanoparticles from gold ions was conducted with caffeic acid as a green reducing agent. The formation of gold nanoparticles was confirmed by spectroscopic and microscopic methods. Spherical nanoparticles with an average diameter of 29.99 ± 7.43 nm were observed in high- resolution transmission electron microscopy and atomic force microscopy images. The newly prepared gold nanoparticles exhibited catalytic activity toward the reduction of 4-nitrophenol to 4-aminophenol in the presence of sodium borohydride. This system enables the preparation of green catalysts using plant natural products as reducing agents, which fulfills the growing need for sustainability initiatives.

  9. Microwave Treated Rapid Hydrothermal Synthesis Of Zno Nano-Flakes Array: The Effect Of Citric Acid As Capping Agent

    NASA Astrophysics Data System (ADS)

    Gopal Ram, S. D.; Ravi, G.; Kulandainathan, M. Anbu

    2010-10-01

    Microwave assisted hydrothermal synthesis of ZnO nanostructures with improved surface area by the addition of Citric Acid (CA) as a metal capping agent is reported. Citric acid is added to the mother precursor in three different concentrations for the preparation of ZnO nanostructure. The influence of the citric acid as a capping agent has been studied both in the preparation of ZnO nanopowders and in the ordered array formation on the precoated ZnO seed layer over glass substrates. The addition of this capping agent has shown up clearly in the morphology of the nanostructures. The X-ray diffraction patterns has shown a diminished crystallinity and a increased full width half maximum (FWHM) in the preferred oriented diffraction peak. The peak broadening is an indication of the reduced crystallite size. This cause of the inhibition in growth is realized to be the effect of capping action of citric acid. The optical property of the ZnO nanostructure was characterized by UV-vis-NIR spectroscopy.

  10. Lactic Acid as a New Therapeutic Peeling Agent in the Treatment of Lifa Disease (Frictional Dermal Melanosis)

    PubMed Central

    Sharquie, Khalifa E; Al-Dhalimi, Muhsin A; Noaimi, Adil A; Al-Sultany, Hussein A

    2012-01-01

    Background: Lifa disease (frictional dermal melanosis) is a common dermatological problem. Full strength lactic acid has been proved to be effective and safe peeling agent in the treatment of melasma. Objective: To assess the effectiveness and the safety of lactic acid chemical peeling in the treatment of lifa disease. Materials and Methods: This open label therapeutic trial was conducted in Department of Dermatology in Najaf and Baghdad Teaching Hospitals, from March 2007-October 2008. Full strength lactic acid (92%, pH 3.5) was used as a peeling agent. The treatment sessions were done every 2 weeks until the desired response was achieved (but not more than 6 sessions). The response to therapy was evaluated by objective and subjective methods. All patients were followed monthly for 3 months after the last treatment session. Results: 52 patients with typical clinical features of lifa disease were included. All patients were slim with prominent bones and low body mass index, and gave history of using the lifa (washing agent) during bathing. The number of sessions ranged from 2-6 sessions. The pigmentation was improved in all patients as revealed by objective and subjective methods, and this response was statistically highly significant. No significant side effects were recorded in all treated patients. The improvement has been sustained without any obvious relapse throughout the follow-up period. Conclusion: Lactic acid peel is a new, non-costly mode of therapy in treating dermal melanosis in patients with lifa disease. PMID:23248362

  11. Pharmacokinetics of chlorogenic acid and corydaline in DA-9701, a new botanical gastroprokinetic agent, in rats.

    PubMed

    Jung, Ji Won; Kim, Ju Myung; Jeong, Jin Seok; Son, Miwon; Lee, Hye Suk; Lee, Myung Gull; Kang, Hee Eun

    2014-07-01

    1.Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been reported. The aim of the present study is to evaluate the pharmacokinetic properties CA and CRD following intravenous and oral administration of pure CA (1-8 mg/kg) or CRD (1.1-4.5 mg/kg) and their equivalent dose of DA-9701 to rats. 2.  Dose-proportional AUC and dose-independent clearance (10.3-12.1 ml/min/kg) of CA were observed following its administration. Oral administration of CA as DA-9701 did not influence the oral pharmacokinetic parameters of CA. Incomplete absorption of CA, its decomposition in the gastrointestinal tract, and/or pre-systemic metabolism resulted in extremely low oral bioavailability (F) of CA (0.478-0.899%). 3.  CRD showed greater dose-normalized AUC in the higher dose group than that in lower dose group(s) after its administration due to saturation of its metabolism via decreased non-renal clearance (by 51.3%) and first-pass extraction. As a result, the F of CRD following 4.5 mg/kg oral CRD (21.1%) was considerably greater than those of the lower dose groups (9.10 and 13.8%). However, oral administration of CRD as DA-9701 showed linear pharmacokinetics as a result of increased AUC and F in lower-dose groups (by 182% and 78.5%, respectively) compared to those of pure CRD. The greater oral AUC of CRD for DA-9701 than for pure CRD could be due to decreased hepatic and/or GI first-pass extraction of CRD by other components in DA-9701.

  12. Evaluation of 9-cis retinoic acid and mitotane as antitumoral agents in an adrenocortical xenograft model.

    PubMed

    Nagy, Zoltán; Baghy, Kornélia; Hunyadi-Gulyás, Éva; Micsik, Tamás; Nyírő, Gábor; Rácz, Gergely; Butz, Henriett; Perge, Pál; Kovalszky, Ilona; Medzihradszky, Katalin F; Rácz, Károly; Patócs, Attila; Igaz, Peter

    2015-01-01

    The available drug treatment options for adrenocortical carcinoma (ACC) are limited. In our previous studies, the in vitro activity of 9-cis retinoic acid (9-cisRA) on adrenocortical NCI-H295R cells was shown along with its antitumoral effects in a small pilot xenograft study. Our aim was to dissect the antitumoral effects of 9-cisRA on ACC in a large-scale xenograft study involving mitotane, 9-cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four groups (i. control, ii. 9-cisRA, iii. mitotane, iv. 9-cisRA + mitotane) for 28 days. Tumor size follow-up, histological and immunohistochemical (Ki-67) analysis, tissue gene expression microarray, quantitative real-time-PCR for the validation of microarray results and to detect circulating microRNAs were performed. Protein expression was studied by proteomics and Western-blot validation. Only mitotane alone and the combination of 9-cisRA and mitotane resulted in significant tumor size reduction. The Ki-67 index was significantly reduced in both 9-cisRA and 9-cisRA+mitotane groups. Only modest changes at the mRNA level were found: the 9-cisRA-induced overexpression of apolipoprotein A4 and down-regulation of phosphodiesterase 4A was validated. The expression of circulating hsa-miR-483-5p was significantly reduced in the combined treatment group. The SET protein was validated as being significantly down-regulated in the combined mitotane+9-cisRA group. 9-cisRA might be a helpful additive agent in the treatment of ACC in combination with mitotane. Circulating hsa-miR-483-5p could be utilized for monitoring the treatment efficacy in ACC patients, and the treatment-induced reduction in protein SET expression might raise its relevance in ACC biology.

  13. Evaluation of 9-cis retinoic acid and mitotane as antitumoral agents in an adrenocortical xenograft model

    PubMed Central

    Nagy, Zoltán; Baghy, Kornélia; Hunyadi-Gulyás, Éva; Micsik, Tamás; Nyírő, Gábor; Rácz, Gergely; Butz, Henriett; Perge, Pál; Kovalszky, Ilona; Medzihradszky, Katalin F; Rácz, Károly; Patócs, Attila; Igaz, Peter

    2015-01-01

    The available drug treatment options for adrenocortical carcinoma (ACC) are limited. In our previous studies, the in vitro activity of 9-cis retinoic acid (9-cisRA) on adrenocortical NCI-H295R cells was shown along with its antitumoral effects in a small pilot xenograft study. Our aim was to dissect the antitumoral effects of 9-cisRA on ACC in a large-scale xenograft study involving mitotane, 9-cisRA and their combination. 43 male SCID mice inoculated with NCI-H295R cells were treated in four groups (i. control, ii. 9-cisRA, iii. mitotane, iv. 9-cisRA + mitotane) for 28 days. Tumor size follow-up, histological and immunohistochemical (Ki-67) analysis, tissue gene expression microarray, quantitative real-time-PCR for the validation of microarray results and to detect circulating microRNAs were performed. Protein expression was studied by proteomics and Western-blot validation. Only mitotane alone and the combination of 9-cisRA and mitotane resulted in significant tumor size reduction. The Ki-67 index was significantly reduced in both 9-cisRA and 9-cisRA+mitotane groups. Only modest changes at the mRNA level were found: the 9-cisRA-induced overexpression of apolipoprotein A4 and down-regulation of phosphodiesterase 4A was validated. The expression of circulating hsa-miR-483-5p was significantly reduced in the combined treatment group. The SET protein was validated as being significantly down-regulated in the combined mitotane+9-cisRA group. 9-cisRA might be a helpful additive agent in the treatment of ACC in combination with mitotane. Circulating hsa-miR-483-5p could be utilized for monitoring the treatment efficacy in ACC patients, and the treatment-induced reduction in protein SET expression might raise its relevance in ACC biology. PMID:26885453

  14. Curcumin Targeted, Polymalic Acid-Based MRI Contrast Agent for the Detection of Aβ Plaques in Alzheimer's Disease.

    PubMed

    Patil, Rameshwar; Gangalum, Pallavi R; Wagner, Shawn; Portilla-Arias, Jose; Ding, Hui; Rekechenetskiy, Arthur; Konda, Bindu; Inoue, Satoshi; Black, Keith L; Ljubimova, Julia Y; Holler, Eggehard

    2015-09-01

    Currently, there is no gadolinium-based contrast agent available for conventional magnetic resonance imaging (MRI) detection of amyloidal beta (Aβ) plaques in Alzheimer's disease (AD). Its timely finding would be vital for patient survival and quality of life. Curcumin (CUR), a common Indian spice effectively binds to Aβ plaques which is a hallmark of AD. To address this binding, we have designed a novel nanoimaging agent (NIA) based on nature-derived poly(β-l-malic acid) (PMLA) containing covalently attached gadolinium-DOTA(Gd-DOTA) and nature-derived CUR. The all-in-one agent recognizes and selectively binds to Aβ plaques and is detected by MRI. It efficiently detected Aβ plaques in human and mouse samples by an ex vivo staining. The method can be useful in clinic for safe and noninvasive diagnosis of AD.

  15. Gallic Acid as a Complexing Agent for Copper Chemical Mechanical Polishing Slurries at Neutral pH

    NASA Astrophysics Data System (ADS)

    Kim, Yung Jun; Kang, Min Cheol; Kwon, Oh Joong; Kim, Jae Jeong

    2011-05-01

    Gallic acid was investigated as a new complexing agent for copper (Cu) chemical mechanical polishing slurries at neutral pH. Addition of 0.03 M gallic acid and 1.12 M H2O2 at pH 7 resulted in a Cu removal rate of 560.73±17.49 nm/min, and the ratio of the Cu removal rate to the Cu dissolution rate was 14.8. Addition of gallic acid improved the slurry performance compared to glycine addition. X-ray photoelectron spectroscopy analysis and contact angle measurements showed that addition of gallic acid enhanced the Cu polishing behavior by suppressing the formation of surface Cu oxide.

  16. Synthesis and biological relationships of 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents.

    PubMed

    Lai, Ya-Yun; Huang, Li-Jiau; Lee, Kuo-Hsiung; Xiao, Zhiyan; Bastow, Kenneth F; Yamori, Takao; Kuo, Sheng-Chu

    2005-01-03

    As part of a continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and their salts were synthesized and evaluated. Preliminary screening showed that carboxylic acid analogs containing a m-fluoro substituted 2-phenyl group displayed the highest in vitro anticancer activity. Activity decreased significantly if a chlorine or methoxy group replaced the fluorine atom. 3'-Fluoro-6-methoxy-2-phenyl-4-quinolone-3-carboxylic acid (68) had the highest in vitro cytotoxic activity among all tested carboxylic acid derivatives and their salts. The mechanism of action may be similar, but not identical, to that of tubulin binding drugs, such as navelbine and taxol. Compound 68 merits further investigation as a novel hydrophilic antimitotic agent.

  17. Effects of Citric Acid and Desensitizing Agent Application on Nonfluorosed and Fluorosed Dentin: An In Vitro Sem Study

    PubMed Central

    Neha, Mahajan; Vandana, Laxman K

    2015-01-01

    Fluorosis is one of the factors which bring about mineralisation changes in a dentinal structure leading to dentin. The purpose of the present study was to compare and evaluate the dentinal tubular changes in fluorosed and nonfluorosed teeth subsequent to the application of citric acid,strontium acetate based sodium fluoride (SAF) using scanning electron microscopy (SEM). Dentin specimens from healthy fluorosed and nonfluorosed teeth were included in the study. Each of them was grouped into acid treated and SAF treatment groups. Using SEM, the photomicrographs (3500x) of dentin specimens were evaluated. Results showed while there was a significant difference in tubular width of partial occlusion ≤ 25%, being more in fluorosed group compared to nonfluorosed group after application SAF. Application of desensitising agents demonstrated higher number of dentinal tubular occlusion and diameter reduction in nonfluorosed dentin compared to fluorosed dentin. Summary: Root biomodification and desensitising agent procedure brings in definite difference between fluorosed and non-fluorosed dentin specimens. PMID:25870716

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

    PubMed

    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.

  19. Biodegradable human serum albumin nanoparticles as contrast agents for the detection of hepatocellular carcinoma by magnetic resonance imaging.

    PubMed

    Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, Hüdayi; Huebner, Frank; Zeuzem, Stefan; Korf, Hans W; Vogl, Thomas J; Rittmeyer, Claudia; Terfort, Andreas; Piiper, Albrecht; Gelperina, Svetlana; Kreuter, Jörg

    2014-05-01

    Tumor visualization by magnetic resonance imaging (MRI) and nanoparticle-based contrast agents may improve the imaging of solid tumors such as hepatocellular carcinoma (HCC). In particular, human serum albumin (HSA) nanoparticles appear to be a suitable carrier due to their safety and feasibility of functionalization. In the present study HSA nanoparticles were conjugated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) using carbodiimide chemistry. The nanoparticles had a uniform spherical shape and a diameter of 235±19nm. For better optical visualization in vitro and in vivo, the HSA-Gd nanoparticles were additionally labeled with rhodamine 123. As shown by confocal microscopy and flow cytometry analysis, the fluorescent nanoparticles were readily taken up by Huh-7 hepatocellular carcinoma cells. After 24h incubation in blood serum, less than 5% of the Gd(III) was released from the particles, which suggests that this nanoparticulate system may be stable in vivo and, therefore, may serve as potentially safe T1 MRI contrast agent for MRI of hepatocellular carcinoma.

  20. Quinolone antimicrobial agents. 1. Versatile new synthesis of 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids.

    PubMed

    Mitscher, L A; Gracey, H E; Clark, G W; Suzuki, T

    1978-05-01

    A flexible reaction sequence has been developed which starts with readily available anthranilic acids or isatoic anhydrides and leads regiospecifically to 1-alkyl-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids after reaction with 1,3-dicarbonyl compounds. The sequence is superior to earlier published methods by allowing electron-releasing and -withdrawing groups in any position on the aro;atic ring, by allowing convenient substitution at C2, and better overall yield. A number of new and known antimicrobial agents were prepared and tested in vitro, demonstrating, inter alia, that substitution of the H at C2 abolished antibacterial activity.

  1. Dose-dependent efficacy and safety toxicology of hydroxypyridinonate actinide decorporation agents in rodents: towards a safe and effective human dosing regimen.

    PubMed

    Bunin, Deborah I; Chang, Polly Y; Doppalapudi, Rupa S; Riccio, Edward S; An, Dahlia; Jarvis, Erin E; Kullgren, Birgitta; Abergel, Rebecca J

    2013-02-01

    Two hydroxypyridinone-containing actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), are being developed for the treatment of internal actinide contamination by chelation therapy. Dose-response efficacy profiles in mice were established for the removal of intravenously injected (238)Pu and (241)Am after parenteral and oral treatment with these chelators. In both cases, presumed efficacious doses promoted substantially greater actinide elimination rates than the currently approved agent, diethylenetriamine-pentaacetic acid, considering two different interspecies scaling methods for the conversion of human doses to equivalent rodent dose levels. In addition, genotoxicity of both ligands was assessed using the Salmonella/ Escherichia coli /microsome plate incorporation test and the Chinese hamster ovary cell chromosome aberration assay, showing that neither ligand is genotoxic, in the presence and absence of metabolic activation. Finally, maximum tolerated dose studies were performed in rats for seven consecutive daily oral administrations with the chelators, confirming the safety of the presumed efficacious doses for 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). The results of these studies add to the growing body of evidence that both decorporation agents have remarkable decorporation efficacy properties and promising safety toxicology profiles. These results are necessary components of the regulatory approval process and will help determine the optimal human dosing regimens for the treatment of internal radionuclide contamination.

  2. Dose-Dependent Efficacy and Safety Toxicology of Hydroxypyridinonate Actinide Decorporation Agents in Rodents: Towards a Safe and EffectiveHuman Dosing Regimen

    PubMed Central

    Bunin, Deborah I.; Chang, Polly Y.; Doppalapudi, Rupa S.; Riccio, Edward S.; An, Dahlia; Jarvis, Erin E.; Kullgren, Birgitta; Abergel, Rebecca J.

    2013-01-01

    Two hydroxypyridinone-containing actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), are being developed for the treatment of internal actinide contamination by chelation therapy. Dose-response efficacy profiles in mice were established for the removal of intravenously injected 238Pu and 241Am after parenteral and oral treatment with these chelators. In both cases, presumed efficacious doses promoted substantially greater actinide elimination rates than the currently approved agent, diethylenetriamine-pentaacetic acid, considering two different interspecies scaling methods for the conversion of human doses to equivalent rodent dose levels. In addition, genotoxicity of both ligands was assessed using the Salmonella/Escherichia coli/microsome plate incorporation test and the Chinese hamster ovary cell chromosome aberration assay, showing that neither ligand is genotoxic, in the presence and absence of metabolic activation. Finally, maximum tolerated dose studies were performed in rats for seven consecutive daily oral administrations with the chelators, confirming the safety of the presumed efficacious doses for 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO). The results of these studies add to the growing body of evidence that both decorporation agents have remarkable decorporation efficacy properties and promising safety toxicology profiles. These results are necessary components of the regulatory approval process and will help determine the optimal human dosing regimens for the treatment of internal radionuclide contamination. PMID:23289385

  3. Gd-DTPA-Dopamine-Bisphytanyl Amphiphile: Synthesis, Characterisation and Relaxation Parameters of the Nanoassemblies and Their Potential as MRI Contrast Agents.

    PubMed

    Gupta, Abhishek; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; de Campo, Liliana; Hwang, Dennis W; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

    2015-09-28

    Here, a new amphiphilic magnetic resonance imaging (MRI) contrast agent, a Gd(III)-chelated diethylenetriaminepentaacetic acid conjugated to two branched alkyl chains via a dopamine spacer, Gd-DTPA-dopamine-bisphytanyl (Gd-DTPA-Dop-Phy), which is readily capable of self-assembling into liposomal nanoassemblies upon dispersion in an aqueous solution, is reported. In vitro relaxivities of the dispersions were found to be much higher than Magnevist, a commercially available contrast agent, at 0.47 T but comparable at 9.40 T. Analysis of variable temperature (17)O NMR transverse relaxation measurements revealed the water exchange of the nanoassemblies to be faster than that previously reported for paramagnetic liposomes. Molecular reorientation dynamics were probed by (1)H NMRD profiles using a classical inner and outer sphere relaxation model and a Lipari-Szabo "model-free" approach. High payloads of Gd(III) ions in the liposomal nanoassemblies made solely from the Gd-DTPA-Dop-Phy amphiphiles, in combination with slow molecular reorientation and fast water exchange makes this novel amphiphile a suitable candidate to be investigated as an advanced MRI contrast agent.

  4. Suberoylanilide hydroxamic acid as a potential therapeutic agent for human breast cancer treatment.

    PubMed Central

    Huang, L.; Pardee, A. B.

    2000-01-01

    BACKGROUND: Suberoylanilide hydroxamic acid (SAHA) is a prototype of the newly developed, second-generation, hybrid polar compounds. It is a novel histone deacetylase inhibitor with high potency for inducing cell differentiation of cultured murine erythroleukemia cells. Studies with SAHA have primarily been performed with hematopoietic tumor cells. Here we extent these studies with SAHA to human breast cancer cell lines in an attempt to find better therapeutic agents for breast cancer treatment. MATERIALS AND METHODS: Human breast cancer cell lines, MCF7, MDA-MB-231, and MDA-MB-435, as well as normal cells, including the normal breast epithelial cell line MCF-10A, and fibroblasts, were treated with SAHA. Cells assayed for cell survival by using trypan blue exclusion assay, colony formation assay, and cell cycle and apoptosis analysis. The effects of SAHA on cell cycle and apoptosis regulatory proteins were examined by Western blots analysis. The identification of additional target genes was carried out by differential display (DD) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: SAHA inhibited clonogenic growth of MCF7, MDA-MB-231, and MDA-MB-435 breast cancer cells. These cells were more sensitive to SAHA-mediated cytotoxic effects than normal breast epithelial cells and fibroblasts. The cytotoxic effects of SAHA on breast cancer cells were manifested by G1 and G2/M cell cycle arrest and eventual apoptosis. The pan-caspase inhibitor, Z-VAD.fmk, blocked SAHA-induced cell death, DNA laddering, and cleavage of poly(ADP-ribose) polymerase, indicating the involvement of caspases in SAHA-mediated apoptosis. In addition, SAHA modulated cell cycle and apoptosis regulatory proteins. For example, cyclin-dependent kinase (CDK) inhibitors p21WAF1/Cip1 and p27Kip1 were induced, and retinoblastoma protein pRb was hypophosphorylated. Moreover, SAHA induced several genes associated with differentiation and/ or growth inhibition. These genes encode gelsolin

  5. A short synthetic route to biologically active (+/-)-daurichromenic acid as highly potent anti-HIV agent.

    PubMed

    Lee, Yong Rok; Wang, Xue

    2005-11-07

    The efficient total synthesis of biologically interesting (+/-)-daurichromenic acid is accomplished starting from 2,4-dihydroxy-6-methylbenzoic acid or 2,4-dihydroxy-6-methylbenzaldehyde in one or two steps.

  6. Comparison of natural humic substances and synthetic ethylenediaminetetraacetic acid and nitrilotriacetic acid as washing agents of a heavy metal-polluted soil.

    PubMed

    Soleimani, Mohsen; Hajabbasi, Mohammad A; Afyuni, Majid; Akbar, Samira; Jensen, Julie K; Holm, Peter E; Borggaard, Ole K

    2010-01-01

    Ethylenediaminetetraacetic acid (EDTA), nitrilotriacetic acid (NTA), and other synthetic polycarboxylic acids have been shown to possess substantial capacity as washing agents of heavy metal-polluted soils, but they are environmentally problematic. Therefore, a sample of natural soluble humic substances (HS) was tested as a possible substitute. The efficiency of HS to extract cadmium (Cd), copper (Cu), and lead (Pb) from a strongly polluted calcareous urban soil was compared with that of EDTA and NTA. The influence of extractant concentration (25-100 mmol L(-1) C), solution/soil ratio (5-100 L kg(-1)), and single-step vs. multistep extraction on heavy metal removal from the soil was investigated. The extracted pools were assessed by sequential extraction. Ethylenediaminetetraacetic acid and NTA extracted up to 86, 77, and 30% of total soil Cd, Cu, and Pb, respectively, whereas HS extracted 44, 53, and 4%. Extracted amounts of Cd, Cu, and Pb increased with increasing extractant concentration and solution/soil ratio in the range 5 to 100 L kg(-1). Single-step extraction removed about the same amounts of the three metals as multiple-step extraction. The metal-extracted pools of the soil depended on the metal and on the extractant. The overall conclusion is that soluble HS can replace synthetic EDTA and NTA as washing agents for Cd- and Cu-polluted soils, whereas HS is not a promising substitute of EDTA or NTA for cleaning Pb-polluted, calcareous soils.

  7. Application of chiral derivatizing agents in the high-performance liquid chromatographic separation of amino acid enantiomers: a review.

    PubMed

    Ilisz, István; Berkecz, Robert; Péter, Antal

    2008-05-12

    The past 20 years has seen an explosive growth in the field of chirality, as illustrated by the rapid progress in the various facets of this intriguing field. The impetus for advances in chiral separation has been highest in the past decade and this still continues to be an area of high focus. This paper reviews indirect separation approaches, i.e. derivatization reactions aimed at creating the basis for the chromatographic resolution of biologically and pharmaceutically important enantiomers, with emphasis on the literature published in the last 12 years. The main aspects of the chiral derivatization of amino acids are discussed, i.e. derivatization on the amino group, transforming the molecules into covalently bonded diastereomeric derivatives through the use of homochiral derivatizing agents. The diastereomers formed (amides, urethanes, urea, thiourea derivatives, etc.) can be separated on achiral stationary phases. The applications are considered, and in some cases different derivatizing agents for the resolution of complex mixtures of proteinogenic d,l-amino acids, non-proteinogenic amino acids and peptides/amino acids from peptide syntheses or microorganisms are compared.

  8. Synthesis of novel oleanolic acid and ursolic acid in C-28 position derivatives as potential anticancer agents.

    PubMed

    Tian, Tian; Liu, Xinyu; Lee, Eung-Seok; Sun, Jingyang; Feng, Zhonghua; Zhao, Longxuan; Zhao, Chunhui

    2017-04-01

    A series of nitrogen-containing derivatives of oleanolic acid and ursolic acid were prepared by a modification at C-28 position via esterification with 2-hydroxyacetic acid followed by amidation with amines, such as piperazine, N-methylpiperazine, and alkane-1, 2-diamines, alkane-1, 4-diamines, alkane-1, 6-diamines. In vitro antiproliferative activities of the compounds prepared towards MCF-7, Hela and A549 cell lines were evaluated by a MTT method to show that OA-5a, OA-5b, OA-5c and UA-5a showed somewhat improved antiproliferative activities against MCF-7, Hela and A549 cells comparing to that of the positive control, gefitinib.

  9. Alteration of tissue disposition of cadmium by chelating agents. [Mice; rats

    SciTech Connect

    Klaassen, C.D.; Waalkes, M.P.; Cantilena, L.R. Jr.

    1984-03-01

    The effect of several chelating agents (diethyldithiocarbamic acid, DDC; nitrilotriacetic acid, NTA; 2,3-dimercaptopropanol, BAL; d,l-penicillamine, PEN; 2,3-dimercaptosuccinic acid, DMSA; ethylenediaminetetraacetic acid, EDTA; and diethylenetriaminepentaacetic acid, DTPA) on the toxicity, distribution and excretion of cadmium (Cd) was determined in mice. When chelators were administered immediately after Cd, significant increases in survival were noted after treatment with DMSA, EDTA, and DTPA. DTPA, followed by EDTA and then DMSA, were consistently the most effective in decreasing the tissue concentrations of Cd and increasing the excretion of Cd. NTA, BAL, DDC and PEN had no beneficial effects. To determine the role of MT in the acute decrease in chelator efficacy following Cd poisoning, rats were injected IV with Cd followed by DTPA at various times after Cd. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal metallothionein (MT) did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D failed to eliminate this decreased DTPA effectiveness. Therefore, it appears that MT does not play an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The effect of repeated daily administration of chelators on the distribution and excretion of Cd was studied by administering chelators daily for 5 days starting 48 hr after Cd. DTPA, EDTA, DMSA and BAL significantly increased the urinary elimination of Cd. Thus, mobilization of Cd into urine occurs with repeated chelation therapy, which may decrease tissue concentrations of Cd and reduce the toxicity of the metal. 4 references, 15 figures, 2 tables.

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

    PubMed

    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

  11. Chiral discrimination of α-hydroxy acids and N-Ts-α-amino acids induced by tetraaza macrocyclic chiral solvating agents by using (1)H NMR spectroscopy.

    PubMed

    Lv, Caixia; Feng, Lei; Zhao, Hongmei; Wang, Guo; Stavropoulos, Pericles; Ai, Lin

    2017-02-21

    In the field of chiral recognition, reported chiral discrimination by (1)H NMR spectroscopy has mainly focused on various chiral analytes with a single chiral center, regarded as standard chiral substrates to evaluate the chiral discriminating abilities of a chiral auxiliary. Among them, chiral α-hydroxy acids, α-amino acids and their derivatives are chiral organic molecules involved in a wide variety of biological processes, and also play an important role in the area of preparation of pharmaceuticals, as they are part of the synthetic process in the production of chiral drug intermediates and protein-based drugs. In this paper, several α-hydroxy acids and N-Ts-α-amino acids were used to evaluate the chiral discriminating abilities of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d by (1)H NMR spectroscopy. The results indicate that α-hydroxy acids and N-Ts-α-amino acids were successfully discriminated in the presence of TAMCSAs 1a-1d by (1)H NMR spectroscopy in most cases. The enantiomers of the α-hydroxy acids and N-Ts-α-amino acids were assigned based on the change of integration of the (1)H NMR signals of the corresponding protons. The enantiomeric excesses (ee) of N-Ts-α-amino acids 11 with different optical compositions were calculated based on the integration of the (1)H NMR signals of the CH3 protons (Ts group) of the enantiomers of (R)- and (S)-11 in the presence of TAMCSA 1b. At the same time, the possible chiral discriminating behaviors have been discussed by means of the Job plots of (±)-2 with TAMCSAs 1b and proposed theoretical models of the enantiomers of 2 and 6 with TAMCSA 1a, respectively.

  12. Development and in-vitro characterization of fish oil oleogels containing benzoyl peroxide and salicylic acid as keratolytic agents.

    PubMed

    Rehman, K; Tan, C M; Zulfakar, M H

    2014-03-01

    Topical keratolytic agents such as benzoyl peroxide (BP) and salicylic acid (SA) are one of the common treatments for inflammatory skin diseases. However, the amount of drug delivery through the skin is limited due to the stratum corneum. The purposes of this study were to investigate the ability of fish oil to act as penetration enhancer for topical keratolytic agents and to determine the suitable gelator for formulating stable fish oil oleogels. 2 types of gelling agents, beeswax and sorbitan monostearate (Span 60), were used to formulate oleogels. To investigate the efficacy of fish oil oleogel permeation, commercial hydrogels of benzoyl peroxide (BP) and salicylic acid (SA) were used as control, and comparative analysis was performed using Franz diffusion cell. Stability of oleogels was determined by physical assessments at 20°C and 40°C storage. Benzoyl peroxide (BP) fish oil oleogels containing beeswax were considered as better formulations in terms of drug permeation and cumulative drug release. All the results were found to be statistically significant (p<0.05, ANOVA) and it was concluded that the beeswax-fish oil combination in oleogel can prove to be beneficial in terms of permeation across the skin and stability.

  13. Inhibition of Thymidine Kinase Activity and Deoxyribonucleic Acid Synthesis in L Cells Infected with the Meningopneumonitis Agent

    PubMed Central

    Lin, Hsiu-San

    1968-01-01

    The activities of enzymes related to deoxyribonucleic acid (DNA) synthesis were studied in uninfected L cells and in L cells infected with Chlamydia psittaci (strain meningopneumonitis). The meningopneumonitis agent multiplied normally but failed to induce the synthesis of thymidine kinase in LM (TK−) cells which contain no thymidine kinase in the uninfected state. It was concluded that this microorganism has no thymidine kinase of its own and that it does not depend on the functioning of the host enzyme for synthesizing its DNA. Exposure of clone 5b L cells to the meningopneumonitis agent was followed by a decline in their thymidine kinase activity to nearly zero levels, whereas the levels of uridine kinase and thymidylate synthetase remained unchanged. Inhibition of thymidine kinase activity in L cells occurred soon after infection and required new protein synthesis by the meningopneumonitis agent. This inhibition occurred before inhibition of host DNA synthesis, but it was not an essential prelude to the latter inhibition. On the basis of this and previous investigations and in light of present knowledge of the mammalian cell cycle, it was postulated that the meningopneumonitis agent inhibits macromolecular synthesis in L cells by preventing the initiation of a new cell cycle. PMID:5724972

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

    PubMed Central

    Hasan, Muhammad Sami; Ahmed, Ifty; Parsons, Andrew; Walker, Gavin; Scotchford, Colin

    2012-01-01

    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. PMID:24955744

  15. Heritable and cancer risks of exposures to anticancer drugs: inter-species comparisons of covalent deoxyribonucleic acid-binding agents.

    PubMed

    Vogel, E W; Barbin, A; Nivard, M J; Stack, H F; Waters, M D; Lohman, P H

    1998-05-25

    In the past years, several methodologies were developed for potency ranking of genotoxic carcinogens and germ cell mutagens. In this paper, we analyzed six sub-classes of covalent deoxyribonucleic acid (DNA) binding antineoplastic drugs comprising a total of 37 chemicals and, in addition, four alkyl-epoxides, using four approaches for the ranking of genotoxic agents on a potency scale: the EPA/IARC genetic activity profile (GAP) database, the ICPEMC agent score system, and the analysis of qualitative and quantitative structure-activity and activity-activity relationships (SARs, AARs) between types of DNA modifications and genotoxic endpoints. Considerations of SARs and AARs focused entirely on in vivo data for mutagenicity in male germ cells (mouse, Drosophila), carcinogenicity (TD50s) and acute toxicity (LD50s) in rodents, whereas the former two approaches combined the entire database on in vivo and in vitro mutagenicity tests. The analysis shows that the understanding and prediction of rank positions of individual genotoxic agents requires information on their mechanism of action. Based on SARs and AARs, the covalent DNA binding antineoplastic drugs can be divided into three categories. Category 1 comprises mono-functional alkylating agents that primarily react with N7 and N3 moieties of purines in DNA. Efficient DNA repair is the major protective mechanism for their low and often not measurable genotoxic effects in repair-competent germ cells, and the need of high exposure doses for tumor induction in rodents. Due to cell type related differences in the efficiency of DNA repair, a strong target cell specificity in various species regarding the potency of these agents for adverse effects is found. Three of the four evaluation systems rank category 1 agents lower than those of the other two categories. Category 2 type mutagens produce O-alkyl adducts in DNA in addition to N-alkyl adducts. In general, certain O-alkyl DNA adducts appear to be slowly repaired, or

  16. Design, synthesis and molecular docking of salicylic acid derivatives containing metronidazole as a new class of antimicrobial agents.

    PubMed

    Guo, Zhi-Hua; Yin, Yong; Wang, Cong; Wang, Peng-Fei; Zhang, Xing-Tao; Wang, Zhong-Chang; Zhu, Hai-Liang

    2015-09-15

    A series of novel salicylic acid derivatives containing metronidazole as Staphylococcus aureus Tyrosyl-tRNA synthetase (TyrRS) inhibitors have been synthesized and evaluated their biology activities as potential antibacterial agents. Among these compounds, compound 5r exhibited the most potent antibacterial activity against Gram-positive (S. aureus ATCC 6538 and Bacillus subtilis ATCC 6633) and Gram-negative (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525) with MICs of 0.39-1.57 μg/mL and showed the most potent S. aureus Tyrosyl-tRNA synthetase inhibitory with 2.3 μM. Docking simulation was performed to insert compound 5r into the crystal structure of S. aureus Tyrosyl-tRNA synthetase active site to determine the probable binding model. These results suggested that compound 5r may be a promising antibacterial agent.

  17. Recent advances in inhibitors of bacterial fatty acid synthesis type II (FASII) system enzymes as potential antibacterial agents.

    PubMed

    Wang, Yi; Ma, Shutao

    2013-10-01

    Bacterial infections are a constant and serious threat to human health. With the increase of multidrug resistance of clinically pathogenic bacteria, common antibiotic therapies have been less effective. Fatty acid synthesis type II (FASII) system enzymes are essential for bacterial membrane lipid biosynthesis and represent increasingly promising targets for the discovery of antibacterial agents with new mechanisms of action. This review highlights recent advances in inhibitors of bacterial FASII as potential antibacterial agents, paying special attention to the activities, mechanisms, and structure-activity relationships of those inhibitors that mainly target β-ketoacyl-ACP synthase, β-ketoacyl-ACP reductase, β-hydroxyacyl-ACP dehydratase, and enoyl-ACP reductase. Although inhibitors with low nanomolar and selective activity against various bacterial FASII have entered clinical trials, further research is needed to expand upon both available and yet unknown scaffolds to identify new FASII inhibitors that may have antibacterial potential, particularly against resistant bacterial strains.

  18. Copolymer of methacrylic acid with its diethylammonium salt: Effective waterproofing agent for oil wells

    SciTech Connect

    Kuznetsova, O.N.; Avvakumova, N.I.

    1992-08-10

    In the development of technology for the copolymerization of methacrylic acid with its diethylammonium salt (MAA-MAA{center_dot}DEA), the polymer-like reaction of polymethacrylic acid (PMAA) with diethylamine (DEA) and the polymerization of MAA in the presence of DEA have been studied. 13 refs., 3 figs., 4 tabs.

  19. Enteric-coated tablet of risedronate sodium in combination with phytic acid, a natural chelating agent, for improved oral bioavailability.

    PubMed

    Kim, Jeong S; Jang, Sun W; Son, Miwon; Kim, Byoung M; Kang, Myung J

    2016-01-20

    The oral bioavailability (BA) of risedronate sodium (RS), an antiresorptive agent, is less than 1% due to its low membrane permeability as well as the formation of non-absorbable complexes with multivalent cations such as calcium ion (Ca(2+)) in the gastrointestinal tract. In the present study, to increase oral BA of the bisphosphonate, a novel enteric-coated tablet (ECT) dosage form of RS in combination with phytic acid (IP6), a natural chelating agent recognized as safe, was formulated. The chelating behavior of IP6 against Ca(2+), including a stability constant for complex formulation was characterized using the continuous variation method. Subsequently, in vitro dissolution profile and in vivo pharmacokinetic profile of the novel ECT were evaluated comparatively with that of the marketed product (Altevia, Sanofi, US), an ECT containing ethylenediaminetetraacetic acid (EDTA) as a chelating agent, in beagle dogs. The logarithm of stability constant for Ca(2+)-IP6 complex, an equilibrium constant approximating the strength of the interaction between two chemicals to form complex, was 19.05, which was 3.9-fold (p<0.05) and 1.7-fold (p<0.05) higher than those of Ca(2+)-RS and Ca(2+)-EDTA complexes. The release profile of RS from both enteric-coated dosage forms was equivalent, regardless of the type of chelating agent. An in vivo absorption study in beagle dogs revealed that the maximum plasma concentration and area under the curve of RS after oral administration of IP6-containing ECT were approximately 7.9- (p<0.05) and 5.0-fold (p<0.05) higher than those of the marketed product at the same dose (35mg as RS). Therefore, our study demonstrates the potential usefulness of the ECT system in combination with IP6 for an oral therapy with the bisphosphonate for improved BA.

  20. Synthesis and Biological Evaluation of Novel Phosphatidylcholine Analogues Containing Monoterpene Acids as Potent Antiproliferative Agents

    PubMed Central

    Gliszczyńska, Anna; Niezgoda, Natalia; Gładkowski, Witold; Czarnecka, Marta; Świtalska, Marta; Wietrzyk, Joanna

    2016-01-01

    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. PMID:27310666

  1. Nucleic acid approaches for detection and identification of biological warfare and infectious disease agents.

    PubMed

    Ivnitski, Dmitri; O'Neil, Daniel J; Gattuso, Anthony; Schlicht, Roger; Calidonna, Michael; Fisher, Rodney

    2003-10-01

    Biological warfare agents are the most problematic of the weapons of mass destruction and terror. Both civilian and military sources predict that over the next decade the threat from proliferation of these agents will increase significantly. In this review we summarize the state of the art in detection and identification of biological threat agents based on PCR technology with emphasis on the new technology of microarrays. The advantages and limitations of real-time PCR technology and a review of the literature as it applies to pathogen and virus detection are presented. The paper covers a number of issues related to the challenges facing biological threat agent detection technologies and identifies critical components that must be overcome for the emergence of reliable PCR-based DNA technologies as bioterrorism countermeasures and for environmental applications. The review evaluates various system components developed for an integrated DNA microchip and the potential applications of the next generation of fully automated DNA analyzers with integrated sample preparation and biosensing elements. The article also reviews promising devices and technologies that are near to being, or have been, commercialized.

  2. Poly(Lactic-co-Glycolic) Acid as a Carrier for Imaging Contrast Agents

    PubMed Central

    Doiron, Amber L.; Homan, Kimberly A.; Emelianov, Stanislav; Brannon-Peppas, Lisa

    2010-01-01

    Purpose With the broadening field of nanomedicine poised for future molecular level therapeutics, nano-and microparticles intended for the augmentation of either single- or multimodal imaging are created with PLGA as the chief constituent and carrier. Methods Emulsion techniques were used to encapsulate hydrophilic and hydrophobic imaging contrast agents in PLGA particles. The imaging contrast properties of these PLGA particles were further enhanced by reducing silver onto the PLGA surface, creating a silver cage around the polymeric core. Results The MRI contrast agent Gd-DTPA and the exogenous dye rhodamine 6G were both encapsulated in PLGA and shown to enhance MR and fluorescence contrast, respectively. The silver nanocage built around PLGA nanoparticles exhibited strong near infrared light absorbance properties, making it a suitable contrast agent for optical imaging strategies such as photoacoustic imaging. Conclusions The biodegradable polymer PLGA is an extremely versatile nano- and micro-carrier for several imaging contrast agents with the possibility of targeting diseased states at a molecular level. PMID:19034628

  3. Improved Cycling Performance of a Si Nanoparticle Anode Utilizing Citric Acid as a Surface-Modifying Agent.

    PubMed

    Nguyen, Cao Cuong; Seo, Daniel M; Chandrasiri, K W D K; Lucht, Brett L

    2016-12-20

    Citric acid and its analogues have been investigated as surface-modifying agents for Si nanoparticle anodes using electrochemical cycling, attenuated total reflectance infrared (ATR IR), and X-ray photoelectron spectroscopy (XPS). A Si nanoparticle anode prepared with citric acid (CA) has better capacity retention than one containing 1,2,3,4-butanetetracarboxylic acid (BA), but both electrodes outperform Si-PVDF. The Si-CA anode has an initial specific capacity of 3530 mA h/g and a first cycle efficiency of 82%. Surprisingly, the Si-CA electrode maintains a high specific capacity of ∼2200 mA h/g after 250 cycles, corresponding to 64% capacity retention, which is similar to the Si prepared with long-chain poly(acrylic acid) (PAA). On the contrary, the silicon electrode prepared with PVDF has a fast capacity fade and retains only 980 mA h/g after 50 cycles. The IR and XPS data show that the Si-CA electrode has an SEI composed primarily of lithium citrate during the first 50 cycles, resulting from the electrochemical reduction of citric acid. Only low concentrations of electrolyte reduction products are observed. The lithium citrate layer derived from CA stabilizes the silicon surface and suppresses electrolyte reduction, which likely contributes to the enhanced cycling performance of the Si nanoparticle anode.

  4. Noncovalent modification of carbon nanotubes with ferrocene-amino acid conjugates for electrochemical sensing of chemical warfare agent mimics.

    PubMed

    Khan, Mohammad A K; Kerman, Kagan; Petryk, Michael; Kraatz, Heinz-Bernhard

    2008-04-01

    The electrochemical detection of chemical warfare agent (CWA) mimics was explored using multiwalled carbon nanotubes (MWCNTs) on indium tin oxide (ITO) surfaces in connection with ferrocene-amino acid conjugates. Various ferrocene-amino acid conjugates were synthesized and utilized as the recognition layer for the detection of CWA mimics. The ferrocene-amino acid conjugates were noncovalently attached to the pretreated MWCNTs on the ITO surface and reacted with CWA mimics, upon which the electrical properties of the MWCNTs and the Fc group were affected significantly. Alternating current voltammetry and capacitance-based detection offered large dynamic ranges for the detection of methylphosphonic acid, diethyl cyanophosphonate, ethylmethylphosphonate, and pinacolyl methylphosphonate in water. Electrochemical measurements showed dramatic changes upon the electrostatic interaction between the CWA mimics and the ferrocene-amino acid conjugates immobilized on MWCNTs on ITO surfaces. Electrochemical sensing in connection with MWCNTs is shown to be a promising analytical tool for the trace-level detection of CWA mimics in aqueous solutions.

  5. 4-Hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as potent anti-tumor agents.

    PubMed

    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.

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

    PubMed

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

    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 20mmol/L, and P ions of 2 to 9mmol/L. PAMAM or NACP bonding agent alone achieved slight remineralization. The PAMAM+NACP group achieved the greatest dentin remineralization p<0.05). At 20days, 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.

  7. [Amino acid chloramines and chlorimines as antiplatelet agents: reactive properties and mechanism of action].

    PubMed

    Murina, M A; Roshchupkin, D I; Petrova, A O; Sergienko, V I

    2009-01-01

    Oxidative modifications of thiols, disulfide, and thioester atomic groups in proteins, peptides, and amino acids induced by chloramines or chloramine derivatives of amino acids and other reactive oxidants are considered. In the case of disulfide and thiol groups, production of sulfur-reactive groups may take place, such as disulphide S-oxides and sulphenic groups. Various chloramines and chloramines differently modify sulfur-containing groups. For example, N,N-dichlorotaurine rapidly modifies the thiolgroup in reduced glutathione and N-chloroglycine readily oxidizes the thioester group in methionine. Amino acid chloramines inhibit platelet aggregation by modifying S-containing centres. Autodecay of amino acid chloramines does not affect aggregation as follows from the absence of positive correlation between chloramines decay rate and antiplatelet activity. N,N-dichlorotaurine and its chlorimine derivatives are characterized by high stability and have good prospects as potential antiaggregants.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27158645

  9. Biodegradable DNA-brush Block Copolymer Spherical Nucleic Acids Enable Transfection Agent-Free Intracellular Gene Regulation

    PubMed Central

    Zhang, Chuan; Hao, Liangliang; Calabrese, Colin M.; Zhou, Yu; Choi, Chung Hang J.; Xing, Hang; Mirkin, Chad A.

    2015-01-01

    A new strategy for synthesizing spherical nucleic acid (SNA) nanostructures from biodegradable DNA block copolymers is reported. Multiple DNA strands are grafted to one end of a polyester chain (poly-caprolactone) to generate an amphiphilic DNA brush block copolymer (DBBC) structure capable of assembling into spherical micelles in aqueous solution. These novel DBBC-based micelle-SNAs exhibit a higher surface density of nucleic acids compared to micelle structures assembled from an analogous linear DNA block copolymer (DBC), which endows them with the ability to more efficiently enter cells without the need for transfection agents. Importantly, the new SNAs show effective gene regulation without observable cellular toxicity in mammalian cell culture. PMID:26297167

  10. Design, Synthesis and Biological Evaluation of Sulfur-Containing 1,1-Bisphosphonic Acids as Antiparasitic Agents

    PubMed Central

    Recher, Marion; Barboza, Alejandro P.; Li, Zhu-Hong; Galizzi, Melina; Ferrer-Casal, Mariana; Szajnman, Sergio H.; Docampo, Roberto; Moreno, Silvia N. J.

    2013-01-01

    As part of our efforts aimed at searching for new antiparasitic agents, 2-alkylmercaptoethyl-1,1-bisphosphonate derivatives were synthesized and evaluated against Trypanosoma cruzi, the etiologic agent of Chagas disease, and Toxoplasma gondii, the responsible agent for toxoplasmosis. Many of these sulfur-containing bisphosphonates were potent inhibitors against the intracellular form of T. cruzi, the clinically more relevant replicative form of this parasite, and tachyzoites of T. gondii targeting T. cruzi or T. gondii farnesyl diphosphate synthases (FPPSs), which constitute valid targets for the chemotherapy of these parasitic diseases. Interestingly, long chain length sulfur-containing bisphosphonates emerged as relevant antiparasitic agents. Taking compounds 37, 38, and 39 as representative members of this class of drugs, they exhibited ED50 values of 15.8 μM, 12.8 μM, and 22.4 μM, respectively, against amastigotes of T. cruzi. These cellular activities matched the inhibition of the enzymatic activity of the target enzyme (TcFPPS) having IC50 values of 6.4 μM, 1.7 μM, and 0.097 μM, respectively. In addition, these compounds were potent anti-Toxoplasma agents. They had ED50 values of 2.6 μM, 1.2 μM, and 1.8 μM, respectively, against T. gondii tachyzoites, while they exhibited a very potent inhibitory action against the target enzyme (TgFPPS) showing IC50 values of 0.024 μM, 0.025 μM, and 0.021 μM, respectively. Bisphosphonates bearing a sulfoxide unit at C-3 were also potent anti-Toxoplasma agents, particularly those bearing long aliphatic chains such as 43–45, which were also potent antiproliferative drugs against tachyzoites of T. gondii. These compounds inhibited the enzymatic activity of the target enzyme (TgFPPS) at the very low nanomolar range. These bisphosphonic acids have very good prospective not only as lead drugs but also as potential chemotherapeutic agents. PMID:23318904

  11. Real-time monitoring of matrix acidizing including the effects of diverting agents

    SciTech Connect

    Hill, A.D.; Zhu, D.

    1996-05-01

    Real-time monitoring of the injection rate and pressure during matrix acidizing provides operators with a way to determine the changing skin factor as stimulation proceeds. Current methods are based either on the assumption of steady-state flow in the region around the wellbore affected by acid injection or on computer solution of the transient flow equations describing the unsteady reservoir flow process occurring during acidizing. In this paper, a new method for real-time monitoring of matrix acidizing, the inverse injectivity vs. superposition time function plot, is presented. This new method can be applied with a spreadsheet computer program or a programmable calculator and accounts for the transient flow effects occurring during matrix acidizing at multiple rates and injection pressures. The evolving skin factor during a matrix treatment is readily obtained from the diagnostic plot. Hypothetical examples show how the inverse injectivity plot can be used to assess the efficiency of stimulation and diversion. Comparisons with previously presented field cases show the new method to be a simple and accurate means of monitoring the evolving skin factor during matrix acidizing.

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

    PubMed

    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.

  13. Research on the interaction of hydrogen-bond acidic polymer sensitive sensor materials with chemical warfare agents simulants by inverse gas chromatography.

    PubMed

    Yang, Liu; Han, Qiang; Cao, Shuya; Huang, Feng; Qin, Molin; Guo, Chenghai; Ding, Mingyu

    2015-06-02

    Hydrogen-bond acidic polymers are important high affinity materials sensitive to organophosphates in the chemical warfare agent sensor detection process. Interactions between the sensor sensitive materials and chemical warfare agent simulants were studied by inverse gas chromatography. Hydrogen bonded acidic polymers, i.e., BSP3, were prepared for micro-packed columns to examine the interaction. DMMP (a nerve gas simulant) and 2-CEES (a blister agent simulant) were used as probes. Chemical and physical parameters such as heats of absorption and Henry constants of the polymers to DMMP and 2-CEES were determined by inverse gas chromatography. Details concerning absorption performance are also discussed in this paper.

  14. Acid reducing agents to neonates – lack of evidence and guidelines

    PubMed Central

    Paulsson, Stina; Eksborg, Staffan; Andersson, Åsa; Nydert, Per; Grahnquist, Lena

    2012-01-01

    Objective The aim of this retrospective study was to investigate the clinical practice, i.e. the frequency of use and the treatment strategies, for acid reducing drugs to neonates in a Swedish hospital. Methods Retrospective reviews of charts and interviews with nurses at the neonatal wards of Karolinska University Hospital were performed to identify difficulties that might occur with drug administration. All patients admitted over a 2-month period were included. Main outcome measure were the number of patients treated with acid reducing drugs and the dosages. Results Nine out of 215 patients (4.2%) received an acid reducing drug. Patients treated with acid reducing drugs had significantly lower birth weight, lower gestational age and longer duration of hospitalization. Eight of the patients were treated with omeprazole. One of these patients started treatment with omeprazole but continued later on with ranitidine. One patient was exclusively treated with ranitidine. The doses of omeprazole (intravenous or oral administration) were within the range 0.16–1.26 mg/kg/day. Conclusions A wide variation in treatment regimens of acid reducing drugs is given to newborn infants. The percentage of treated children was much lower than earlier reports from the US and UK. No conclusions can be drawn as to whether the doses and dosing intervals used give sufficient acid suppression, since the effect of the therapy was not recorded. The present study is only retrospective and data are not truly comparable with other studies. Further studies are therefore warranted to evaluate effective doses and pharmacokinetics of acid reducing drugs in newborn infants. PMID:27536424

  15. Structural characterization of 1,3-propanedithiols that feature carboxylic acids: Homologues of mercury chelating agents.

    PubMed

    Sattler, Wesley; Palmer, Joshua H; Bridges, Christy C; Joshee, Lucy; Zalups, Rudolfs K; Parkin, Gerard

    2013-11-12

    The molecular structures of a series of 1,3-propanedithiols that contain carboxylic acid groups, namely rac- and meso-2,4-dimercaptoglutaric acid (H4DMGA) and 2-carboxy-1,3-propanedithiol (H3DMCP), have been determined by X-ray diffraction. Each compound exhibits two centrosymmetric intermolecular hydrogen bonding interactions between pairs of carboxylic acid groups, which result in a dimeric structure for H3DMCP and a polymeric tape-like structure for rac- and meso-H4DMGA. Significantly, the hydrogen bonding motifs observed for rac- and meso-H4DMGA are very different to those observed for the 1,2-dithiol, rac-2,3-dimercaptosuccinic acid (rac-H4DMSA), in which the two oxygen atoms of each carboxylic acid group hydrogen bond to two different carboxylic acid groups, thereby resulting in a hydrogen bonded sheet-like structure rather than a tape. Density functional theory calculations indicate that 1,3-dithiolate coordination to mercury results in larger S-Hg-S bond angles than does 1,2-dithiolate coordination, but these angles are far from linear. As such, κ(2)-S2 coordination of these dithiolate ligands is expected to be associated with mercury coordination numbers of greater than two. In vivo studies demonstrate that both rac-H 4 DMGA and H3DMCP reduce the renal burden of mercury in rats, although the compounds are not as effective as either 2,3-dimercaptopropane-1-sulfonic acid (H3DMPS) or meso-H4DMSA.

  16. A new facile route for synthesizing of graphene oxide using mixture of sulfuric-nitric-phosphoric acids as intercalating agent

    NASA Astrophysics Data System (ADS)

    Panwar, Vinay; Chattree, Ananya; Pal, Kaushik

    2015-09-01

    In this work, graphene oxide (GO) has been prepared through three different processes namely, eco-friendly Hummers method, modification in improved Hummers method and a new approach. This new approach has been designed by changing some processing parameters and intercalating agent for significant reduction in processing time and to improve the quantity of GO in comparison to the other two methods. This has been achieved through better oxidization of graphite using nitric-sulfuric acid (HNO3-H2SO4) as intercalating agent. X-ray diffraction (XRD), Field Emission Scanning Electron Microscopy (FESEM), Energy-dispersive X-ray spectroscopy (EDX), Raman spectroscopy, Atomic Force Microscopy (AFM), X-ray photoelectron spectroscopy (XPS), UV-visible spectroscopy, and Thermogravimetric analysis (TGA) are used to characterize the GO prepared through different processes. These characterizations have confirmed an improved exfoliation of graphite, using addition of HNO3 in intercalating agent, in a short processing time and bring on higher yield of GO via this new process.

  17. Development and Evaluation of a Nanoemulsion Containing Ursolic Acid: a Promising Trypanocidal Agent : Nanoemulsion with Ursolic Acid Against T. cruzi.

    PubMed

    Vargas de Oliveira, Erika Cristina; Carneiro, Zumira Aparecida; de Albuquerque, Sérgio; Marchetti, Juliana Maldonado

    2017-02-21

    Over a hundred years after the discovery of Chagas disease, this ailment continues to affect thousands of people. For more than 40 years, only two drugs have been available to treat it. Ursolic acid is a naturally occurring terpene that has shown a good trypanocidal action. However, the hydrophobicity of this compound presents a challenge for the development of proper delivery systems. Nanostructured systems are a prominent in delivering lipophilic drugs. Thus, a nanoemulsion containing ursolic acid was developed and had its trypanocidal activity and cytotoxicity evaluated. Pseudo-ternary phase diagrams and hydrophilic-lipophilic balance (HLB) system were used in the development. The system was stable throughout 90 days of testing, as evidenced by turbidimetry analysis and measurements of the droplet size (57.3 nm) and polydispersity index (0.24). Fourier transform infrared spectroscopy and mass spectrometry evidenced drug's integrity in the formulation. An in vitro dissolution profile showed 75% of ursolic acid release after 5 min from the nanoemulsion into the alkaline dissolution medium, while only 20% could be released from a physical mixture after 2 h. Trypanocidal activity and cytotoxicity were evaluated on the CL Brener strain and LLC-MK2 (monkey kidney) fibroblast by chlorophenol red-β-D-galactoside (CPRG) method. Biological studies showed that the developed formulation was nontoxic and effective against replicant forms of the parasite. A stable and efficient nanoemulsion could be developed to improve the delivery of a promising drug to treat a threatening illness such as Chagas disease.

  18. Citrus Flavanones Affect Hepatic Fatty Acid Oxidation in Rats by Acting as Prooxidant Agents

    PubMed Central

    Constantin, Rodrigo Polimeni; do Nascimento, Gilson Soares; Constantin, Renato Polimeni; Salgueiro, Clairce Luzia; Bracht, Adelar; Ishii-Iwamoto, Emy Luiza; Yamamoto, Nair Seiko

    2013-01-01

    Citrus flavonoids have a wide range of biological activities and positive health effects on mammalian cells because of their antioxidant properties. However, they also act as prooxidants and thus may interfere with metabolic pathways. The purpose of this work was to evaluate the effects of three citrus flavanones, hesperidin, hesperetin, and naringenin, on several parameters linked to fatty acid oxidation in mitochondria, peroxisomes, and perfused livers of rats. When exogenous octanoate was used as substrate, hesperetin and naringenin reduced the mitochondrial NADH/NAD+ ratio and stimulated the citric acid cycle without significant changes on oxygen uptake or ketogenesis. When fatty acid oxidation from endogenous sources was evaluated, hesperetin and naringenin strongly reduced the mitochondrial NADH/NAD+ ratio. They also inhibited both oxygen uptake and ketogenesis and stimulated the citric acid cycle. Hesperidin, on the other hand, had little to no effect on these parameters. These results confirm the hypothesis that citrus flavanones are able to induce a more oxidised state in liver cells, altering parameters related to hepatic fatty acid oxidation. The prooxidant effect is most likely a consequence of the ability of these substances to oxidise NADH upon production of phenoxyl radicals in the presence of peroxidases and hydrogen peroxide. PMID:24288675

  19. Influence of Glacial Acetic Acid and Nitric Acid as a Chelating Agent in Sol-gel Process to the Nanostructured Titanium Dioxide Thin Films

    NASA Astrophysics Data System (ADS)

    Ahmad, M. K.; Rusop, M.

    2009-06-01

    The comparison between different chelating agents in sol-gel process for deposition of nanostructured Titanium Dioxide (TiO2) thin film has been studied. Glacial Acetic Acid (GA) and Nitric Acid (NA) were used in 0.2 M of concentration. The effects to the structural, electrical and optical properties have been studied. The effects of these properties were characterized using X-Ray Diffractometer (XRD), 2-point probe I-V measurement and UV-Vis-NIR Spectrophotometer. For electrical properties, it showed that nanostructured TiO2 thin film that using GA (TF-GA) as chelating agent gives better low sheet resistance compare to nanostructured TiO2 thin film using NA (TF-NA). From XRD results, it indicates that no significantly different between both TiO2 thin film. Both of thin films have crystalline anatase phase at 2θ degree 25.8° which corresponded to (101) orientation. For optical properties, sol-gel using GA has slightly higher in transmittance spectra properties but both of films fully absorbed UV light at 300 nm of wavelength. As for optical band gap, both sol-gels using GA and NA has similar optical band gap which is 3.27 eV.

  20. Synthesis of Ba 2YCu 3O 7 by the SCD method using amino acid salt reducing agents

    NASA Astrophysics Data System (ADS)

    Kourtakis, K.; Robbins, M.; Gallagher, P. K.

    1990-01-01

    The anionic oxidation-reduction or SCD method relies on an internal oxidation-reduction reaction which converts spray-dried precursors into intimately mixed and highly reactive metal oxide powders. Earlier studies focused on precursor mixtures containing oxidizing components such as NO -3 salts with reducing salts (RCOO -, where R is H, CH 3, or CH 2CH 3) which react to form Ba 2YCu 3O 7 powder. In this work, amino acid reducing agents are used. The impact of the functional group change, in the reducing agent of the {NO -3}/{amino acid} precursors, is shown by DSC to result in sharp (and therefore rapid) oxidation-reduction reactions which occur at lower temperatures. The trend in reaction temperature correlates inversely with the expected basicity of the amino group in the series (numbers in parentheses represent mole ratios): {CH 3CH(NH 2)COO -}/{NO -3} ( {4}/{9}) = 206° C > {NH 2CH 2COO -}/{NO -3} ( {4}/{9}) = 195° C > {NH 2CH 2CH 2COO -}/{NO -3} ( {4}/{9}) = 191° C. The mixed oxide product is highly reactive and can be converted to single-phase Ba 2YCu 3O x when fired at 900-910°C for 10 min in flowing oxygen.

  1. Quantification of phosphatidylserine, phosphatidic acid and free fatty acids in an ultrasound contrast agent by normal-phase high-performance liquid chromatography with evaporative light scattering detection.

    PubMed

    Hvattum, Erlend; Uran, Steinar; Sandbaek, Anne Gunvor; Karlsson, Anders A; Skotland, Tore

    2006-10-11

    Sonazoid is a new contrast agent for ultrasound imaging. The product is an aqueous suspension of perfluorobutane microbubbles coated with phospholipids obtained from hydrogenated egg phosphatidylserine (H-EPS). A normal-phase high-performance liquid chromatographic (HPLC) method with evaporative light scattering detection was developed for quantification of free fatty acids, phosphatidylserine and phosphatidic acid in H-EPS and Sonazoid. Separation of the lipids was carried out on an HPLC diol column and a gradient of chloroform and methanol with 0.2% formic acid titrated to pH 7.5 with ammonia. The calibration standards contained stearic acid, distearoyl-phosphatidic acid (DSPA) and distearoyl-phosphatidylserine (DSPS) in the concentration range of 0.016-1.0mg/ml (0.4-25microg injected). The method was validated with a limit of quantification of the three lipids set to 0.4microg (approximately 20-60microM). The best fit of the three calibration curves were obtained when the logarithmic transformed theoretical lipid concentration was plotted against the logarithmic transformed area under the peak and fitted to a second order polynomial equation. Stearic acid, DSPA and DSPS were analysed with an intermediate precision ranging from 4.4% to 5.3% R.S.D. and they were extracted from an aqueous suspension with a recovery ranging from 103.3% to 113.3%. The sum of total phospholipid concentration determined in H-EPS ranged from 96.4% to 103.2% of the theoretical values. The lipids in the ultrasound product were quantitated with a repeatability ranging from 6.2% to 11.7% R.S.D.

  2. Label-free functional nucleic acid sensors for detecting target agents

    DOEpatents

    Lu, Yi; Xiang, Yu

    2015-01-13

    A general methodology to design label-free fluorescent functional nucleic acid sensors using a vacant site approach and an abasic site approach is described. In one example, a method for designing label-free fluorescent functional nucleic acid sensors (e.g., those that include a DNAzyme, aptamer or aptazyme) that have a tunable dynamic range through the introduction of an abasic site (e.g., dSpacer) or a vacant site into the functional nucleic acids. Also provided is a general method for designing label-free fluorescent aptamer sensors based on the regulation of malachite green (MG) fluorescence. A general method for designing label-free fluorescent catalytic and molecular beacons (CAMBs) is also provided. The methods demonstrated here can be used to design many other label-free fluorescent sensors to detect a wide range of analytes. Sensors and methods of using the disclosed sensors are also provided.

  3. Effect of sweetening agents in acidic beverages on associated erosion lesions.

    PubMed

    Bassiouny, Mohamed A

    2012-01-01

    Accurate diagnosis of erosion defects caused by acidic beverages is essential when designing a comprehensive management strategy that includes combating possible recurrence. The manifestations of erosion lesions associated with acidic beverages are diverse, as seen in the differences and similarities of lesions associated with various regular and diet varieties of beverages. Erosion lesions caused by regular sugar-sweetened beverages display signs similar to dental caries, while lesions resulting from diet, non-sugar-sweetened soft drinks have defects similar to mechanical wear of the dentition. Aggravating factors such as toothbrushing or compromised oral home care could influence the features of erosion lesions. These diverse characteristics of erosion lesions could make identification difficult. This article describes pertinent signs of erosion defects associated with the regular and diet varieties of acidic beverages and discusses their causative factors. This information is designed to avert an improper diagnosis that would derail any restorative intervention and alter a proper preventive management course.

  4. Citric acid and ethylene diamine tetra-acetic acid as effective washing agents to treat sewage sludge for agricultural reuse.

    PubMed

    Ren, Xianghao; Yan, Rui; Wang, Hong-Cheng; Kou, Ying-Ying; Chae, Kyu-Jung; Kim, In S; Park, Yong-Jin; Wang, Ai-Jie

    2015-12-01

    This paper presents the effects of different concentrations of citric acid (CA) and ethylene diamine tetra-acetic acid (EDTA) when used as additive reagents for the treatment of sewage sludge for agricultural use. Herein, both the retention of nutrients and removal of metals from the sewage sludge are examined. The average removal rate for the metals after treatment by CA decreased in the order Cu>Pb>Cd>Cr>Zn, while the rates after treatment by EDTA decreased in the order of Pb>Cu>Cr>Cd>Zn. After treatment with CA and EDTA, total nitrogen and total phosphorus concentrations in the sludge decreased, while the content of available nitrogen and Olsen-P increased. In addition, a multi-criteria analysis model-fuzzy analytic network process method (with 3 main factors and 12 assessment sub-factors) was adopted to evaluate the effectiveness of different treatment methods. The results showed that the optimal CA and EDTA concentrations for sewage sludge treatment were 0.60 and 0.125 mol/L, respectively.

  5. Synthesis and biological evaluation of new heteroaryl carboxylic acid derivatives as anti-inflammatory-analgesic agents.

    PubMed

    Abouzid, Khaled Abouzid Mohamed; Khalil, Nadia Abdalla; Ahmed, Eman Mohamed; Zaitone, Sawsan Abo-Bakr

    2013-01-01

    A series of nicotinic acid derivatives structurally related to niflumic acid and certain pyridazine-containing compounds have been synthesized and characterized by analytical and spectral data. All compounds were screened for their potential analgesic and anti-inflammatory activities. The compounds which displayed analgesic and anti-inflammatory activities were tested for ulcerogenicity and screened for in vivo inhibition of certain inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2). Compounds 1c, 2a, 2b, and 5a have shown potent analgesic and anti-inflammatory activities.

  6. New tuberculostatic agents targeting nucleic acid biosynthesis: drug design using QSAR approaches.

    PubMed

    Bueno, Renata V; Braga, Rodolpho C; Segretti, Natanael D; Ferreira, Elizabeth I; Trossini, Gustavo H G; Andrade, Carolina H

    2014-01-01

    Worldwide, tuberculosis (TB) is the leading cause of death among curable infectious diseases. The emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB is a growing global health concern and there is an urgent need for new anti-TB drugs. Enzymes involved in DNA and ATP biosynthesis are potential targets for tuberculostatic drug design, since these enzymes are essential for Mycobacterium tuberculosis growth. This review presents the current progress and applications of structure-activity relationship analysis for the discovery of innovative tuberculostatic agents as inhibitors of ribonucleotide reductase, DNA gyrase, ATP synthase, and thymidylate kinase enzymes, highlighting present challenges and new opportunities in TB drug design.

  7. Influence of chelating agents on the distribution and excretion of cadmium in rats

    SciTech Connect

    Planas-Bohne, F.; Lehmann, M.

    1983-03-15

    The effects of the chelating agents CaNa2-ethylenediaminetetraacetate (EDTA), CaNa3-diethylenetriaminepentaacetate (DTPA), 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropanol (BAL), and 2,3-dimercaptopropane-1-sulfonate (DMPS) and of the lipophilic chelating agents Puchel, Puchel-bisamidocysteineethyl ester (Puch-D), and EDTA-bis-amidocysteineethyl ester (EDTA-D) on the distribution of iv injected Cd were studied in male Sprague-Dawley rats. The chelating agents were injected iv as single doses given 10 sec, 1 hr, or 3 hr after 3 mumol/kg Cd + 115mCd. When the chelating agents were injected within 10 sec after the metal, all agents reduced the total body cadmium burden by varying extents ranging from 3% of that in untreated control rats after 0.01 mmol BAL/kg to 94% following 0.1 mmol DTPA/kg. When given 1 hr after Cd injection, the efficacy of all the agents tested was markedly reduced or abolished; at this time only Puchel and Puch-D provoked significant reductions in the body burden of Cd by 21 and 32%, respectively. When treatment was delayed until 3 hr after Cd injection, only Puch-D was able to reduce the body and liver burden of the metal by 14 and 9%, respectively. Combined treatment with Puchel + DTPA, BAL + DTPA, or BAL + DMPS did not enhance Cd removal to an extent greater than that expected from the equivalent dose of the more effective agent of that pair alone. Repeated administration of DTPA, 20 X 0.1 mmol/kg, during 4 weeks by ip or po administration of the same dose in the drinking water over 4 weeks, was no no more effective than the first dose of the chelating agent alone. Gel chromatographic studies of the distribution of Cd among the proteins of the liver cytosol in treated and untreated animals indicate that neither DTPA nor Puchel was able to release Cd from the metallothionein complex.

  8. Synthesis and characteristics of (Hydrogenated) ferulic acid derivatives as potential antiviral agents with insecticidal activity

    PubMed Central

    2013-01-01

    Background Plant viruses cause many serious plant diseases and are currently suppressed with the simultaneous use of virucides and insecticides. The use of such materials, however, increases the amounts of pollutants in the environment. To reduce environmental contaminants, virucides with insecticidal activity is an attractive option. Results A series of substituted ferulic acid amide derivatives 7 and the corresponding hydrogenated ferulic acid amide derivatives 13 were synthesized and evaluated for their antiviral and insecticidal activities. The majority of the synthesized compounds exhibited good levels of antiviral activity against the tobacco mosaic virus (TMW), with compounds 7a, 7b and 7d in particular providing higher levels of protective and curative activities against TMV at 500 μg/mL than the control compound ribavirin. Furthermore, these compounds displayed good insecticidal activities against insects with piercing-sucking mouthparts, which can spread plant viruses between and within crops. Conclusions Two series of ferulic acid derivatives have been synthesized efficiently. The bioassay showed title compounds not only inhibit the plant viral infection, but also prevented the spread of plant virus by insect vectors. These findings therefore demonstrate that the ferulic acid amides represent a new template for future antiviral studies. PMID:23409923

  9. Sugar beet pulp and poly(lactic acid) composites using methylene diphenyl diisocyanate as coupling agent

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Composites from sugar beet pulp (SBP) and poly(lactic acid) (PLA) were extruded in the presence of polymeric methylene diphenyl diisocyanate (pMDI). SBP particles were evenly distributed within the PLA matrix phase as revealed by confocal fluorescence microscopic analysis. The resultant composites w...

  10. Long-acting contraceptive agents: esters of norethisterone with alkoxy- and halogeno-substituted carboxylic acids.

    PubMed

    Shafiee, A; Vossoghi, M; Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; Sotheeswaran, S

    1983-03-01

    The chemical synthesis and physical data of several new esters of norethisterone (17 alpha-ethynyl-17 beta-hydroxyestr-4-en-3-one) are reported, which contain either a chloro- or an alkoxy-group as a substituent in the acid side-chain.

  11. Barbituric acid-based magnetic N-halamine nanoparticles as recyclable antibacterial agents.

    PubMed

    Dong, Alideertu; Sun, Yue; Lan, Shi; Wang, Qin; Cai, Qian; Qi, Xiuzhen; Zhang, Yanling; Gao, Ge; Liu, Fengqi; Harnoode, Chokto

    2013-08-28

    Novel recyclable bactericidal materials, barbituric acid-based magnetic N-halamine nanoparticles (BAMNH NPs), were fabricated by coating of magnetic silica nanoparticles (MS NPs) with barbituric acid-based N-halamine by the aid of the radical polymerization. The sterilizing effect on the bacterial strain is investigated by incubating Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis). The as-prepared BAMNH NPs exhibit higher biocidal activity than the bulk powder barbituric acid-based N-halamine due to the high activated surface area. The structural effect of N-halamine on antimicrobial performance was fully clarified through the comparison between BAMNH NPs and hydantoin-based magnetic N-halamine nanoparticles (HMNH NPs). BAMNH NPs exhibited promising stability toward repeated washing and long-term storage. BAMNH NPs with different chlorine content were comparatively chosen to investigate the influence of chlorine content on the antimicrobial activity. An antibacterial recycle experiment revealed that no significant change occurred in the structure and antibacterial efficiency of BAMNH NPs after five recycle experiments. The combination of barbituric acid-based N-halamine with magnetic component results in an obvious synergistic effect and facilitates the repeated antibacterial applications, providing potential and ideal candidates for sterilization or even for the control of disease.

  12. Wood ants produce a potent antimicrobial agent by applying formic acid on tree-collected resin.

    PubMed

    Brütsch, Timothée; Jaffuel, Geoffrey; Vallat, Armelle; Turlings, Ted C J; Chapuisat, Michel

    2017-04-01

    Wood ants fight pathogens by incorporating tree resin with antimicrobial properties into their nests. They also produce large quantities of formic acid in their venom gland, which they readily spray to defend or disinfect their nest. Mixing chemicals to produce powerful antibiotics is common practice in human medicine, yet evidence for the use of such "defensive cocktails" by animals remains scant. Here, we test the hypothesis that wood ants enhance the antifungal activity of tree resin by treating it with formic acid. In a series of experiments, we document that (i) tree resin had much higher inhibitory activity against the common entomopathogenic fungus Metarhizium brunneum after having been in contact with ants, while no such effect was detected for other nest materials; (ii) wood ants applied significant amounts of endogenous formic and succinic acid on resin and other nest materials; and (iii) the application of synthetic formic acid greatly increased the antifungal activity of resin, but had no such effect when applied to inert glass material. Together, these results demonstrate that wood ants obtain an effective protection against a detrimental microorganism by mixing endogenous and plant-acquired chemical defenses. In conclusion, the ability to synergistically combine antimicrobial substances of diverse origins is not restricted to humans and may play an important role in insect societies.

  13. Augmenting antifungal activity of oxidizing agent with kojic acid: Control of Penicillium strains infecting crops

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oxidative treatment is a strategy for preventing Penicillium contamination in foods or crops. Antifungal efficacy of oxidant [hydrogen peroxide (H2O2)], biotic effector [kojic acid (KA)] and abiotic stress (heat), alone or in combination, was investigated in Penicillium. The levels of antifungal int...

  14. Boric acid: a potential chemoprotective agent against aflatoxin b1 toxicity in human blood

    PubMed Central

    Geyikoglu, Fatime

    2010-01-01

    Aflatoxin B1 is the most potent pulmonary and hepatic carcinogen. Since the eradication of Aflatoxin B1 contamination in agricultural products has been difficult, the use of natural or synthetic free radical scavengers could be a potential chemopreventive strategy. Boric acid is the major component of industry and its antioxidant role has recently been reported. The present study assessed, for the first time, the effectiveness of boric acid following exposure to Aflatoxin B1 on human whole blood cultures. The biochemical characterizations of glutathione and some enzymes have been carried out in erythrocytes. Alterations in malondialdehyde level were determined as an index of oxidative stress. The sister-chromatid exchange and micronucleus tests were performed to assess DNA damages in lymphocytes. Aflatoxin B1 treatment significantly reduced the activities of antioxidants by increasing malondialdehyde level (30.53 and 51.43%) of blood, whereas, the boric acid led to an increased resistance of DNA to oxidative damage induced by Aflatoxin B1 in comparison with control values (P < 0.05). In conclusion, the support of boric acid was especially useful in Aflatoxin-toxicated blood. Thus the risk on tissue targeting of Aflatoxin B1 could be reduced ensuring early recovery from its toxicity. PMID:20431944

  15. Battery acid--an agent of attempted suicide in black South Africans.

    PubMed

    Wilson, D A; Wormald, P J

    1995-06-01

    Over a 36-month period 27 black adults, who had taken battery acid in apparent suicide attempts, were admitted to a major South African general hospital for assessment and treatment. There were no deaths. Patient features included limited schooling, unemployment and a male/female ratio of 2.4:1. Triggers were minor to moderate stressors (mainly domestic arguments) in 23 patients. Nine had a diagnosable psychiatric disorder and 5 required further psychiatric hospitalisation following discharge from the general hospital. The reported high mortality rate from acid ingestion was not observed; however, 4 patients required surgical intervention to deal with stricture formation. The average duration of stay was 7.6 days. There were no repeat suicide attempts during the study period.

  16. A-ring modified betulinic acid derivatives as potent cancer preventive agents.

    PubMed

    Hung, Hsin-Yi; Nakagawa-Goto, Kyoko; Tokuda, Harukuni; Iida, Akira; Suzuki, Nobutaka; Bori, Ibrahim D; Qian, Keduo; Lee, Kuo-Hsiung

    2014-02-01

    Ten new 3,4-seco betulinic acid (BA) derivatives were designed and synthesized. Among them, compounds 7-15 exhibited enhanced chemopreventive ability in an in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA) induced Epstein-Barr virus early antigen (EBV-EA) activation assay in Raji cells. Specifically, analogs with a free C-28 carboxylic acid, including 7, 8, 11, and 13, inhibited EBV-EA activation significantly. The most potent compound 8 displayed 100% inhibition at 1×10(3) mol ratio/TPA and 73.4%, 35.9%, and 8.4% inhibition at 5×10(2), 1×10(2), and 1×10 mol ratio/TPA, respectively, comparable with curcumin at high concentration and better than curcumin at low concentration. The potent chemopreventive activity of novel seco A-ring BAs (8 and 11) was further confirmed in an in vivo mouse skin carcinogenesis assay.

  17. Potential cerebral perfusion agents: synthesis and evaluation of a radioiodinated vinylalkylbarbituric acid analogue

    SciTech Connect

    Srivastava, P.C.; Callahan, A.P.; Cunningham, E.B.; Knapp, F.F. Jr.

    1983-05-01

    A new iodinated barbiturate has been prepared. Treatment of 5-chloropentyne and propargyl bromide with diethyl 2-ethyl-2-sodiomalonate (DESM) provided diethyl 2-ethyl-2-(1-pentyn-5-yl)malonate (3) and diethyl 2-ethyl-2-propargylmalonate (4), respectively. Similar condensation of DESM with (E)-(5-iodo-1-penten-1-yl)boronic acid (9) or the reaction of catecholborane with 3 provided diethyl (E)-2-ethyl-2-(1-borono-1-penten-5-yl)malonate (8). The direct sodium iodide-chloramine-T iodination of 8 or the treatment of (E)-1,5-diiodo-1-pentene (10) with DESM provided diethyl (E)-2-ethyl-2-(1-iodo-1-penten-5-yl)malonate (11). The condensation of functionalized malonates 3, 4, and 11 with urea in the presence of a base provided the corresponding barbiturates, 5-ethyl-5-(1-pentyn-5-yl)-(5), 5-ethyl-5-propargyl- (6), and (E)-5-ethyl-5-(1-iodo-1-penten-5-yl)barbituric acid (12), respectively. (E)-6-(Ethoxycarbonyl)-1-iodo-1-octene-6-carboxylic acid (13) was isolated as the hydrolytic byproduct of 11. Compound 13 decarboxylated under vacuum to provide ethyl (E)-1-iodo-1-octene-6-carboxylate (14). The /sup 125/I-labeled congeners of 12 and 13 were synthesized in the same manner and evaluated in rats. The barbiturate 12 exhibited significant brain uptake (approximately 1% dose after 5 min), demonstrating that iodinated barbiturates freely cross the intact blood-brain barrier.

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

    PubMed

    Ooi, Der Jiun; Chan, Kim Wei; Sarega, Nadarajan; Alitheen, Noorjahan Banu; Ithnin, Hairuszah; Ismail, Maznah

    2016-06-17

    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.

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

    PubMed

    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.

  20. Evaluation of physicochemical properties, skin permeation and accumulation profiles of salicylic acid amide prodrugs as sunscreen agent.

    PubMed

    Yan, Yi-Dong; Sung, Jun Ho; Lee, Dong Won; Kim, Jung Sun; Jeon, Eun-Mi; Kim, Dae-Duk; Kim, Dong Wuk; Kim, Jong Oh; Piao, Ming Guan; Li, Dong Xun; Yong, Chul Soon; Choi, Han Gon

    2011-10-31

    Various amide prodrugs of salicylic acid were synthesised, and their physicochemical properties including lipophilicity, chemical stability and enzymatic hydrolysis were investigated. In vivo skin permeation and accumulation profiles were also evaluated using a combination of common permeation enhancing techniques such as the use of a supersaturated solution of permeants in an enhancer vehicle, a lipophilic receptor solution, removal of the stratum corneum and delipidisation of skin. Their capacity factor values were proportional to the degree of carbon-carbon saturation in the side chain. All these amides were highly stable in acetonitrile and glycerine. Amide prodrugs were converted to salicylic acid both in hairless mouse liver and skin homogenates. N-dodecyl salicylamide (C12SM) showed the lowest permeation of salicylic acid in skin compared to the other prodrugs, probably due to its low aqueous solubility. It had a high affinity for the stratum corneum and its accumulation was restricted to only the uppermost layer of skin. Thus, this amide prodrug could be a safer topical sunscreen agent with minimum potential for systemic absorption.

  1. Carboxylic Acid-Functionalized Conducting-Polymer Nanotubes as Highly Sensitive Nerve-Agent Chemiresistors

    NASA Astrophysics Data System (ADS)

    Kwon, Oh Seok; Park, Chul Soon; Park, Seon Joo; Noh, Seonmyeong; Kim, Saerona; Kong, Hye Jeong; Bae, Joonwon; Lee, Chang-Soo; Yoon, Hyeonseok

    2016-09-01

    Organophosphates are powerful inhibitors of acetylcholinesterase, which is critical to nerve function. Despite continuous research for detecting the highly toxic organophosphates, a new and improved methodology is still needed. Herein we demonstrate simple-to-fabricate chemiresistive gas sensors using conducting-polymer polypyrrole (PPy) nanotube transducers, which are chemically specific and capable of recognizing sub-ppb concentrations (ca. 0.5 ppb) of dimethyl methylphosphonate (DMMP), a simulant of nerve agent sarin. Interestingly, the introduction of carboxylic groups on the surface of PPy nanotube transistors resulted in enhanced sensitivity to DMMP via intermolecular hydrogen bonding. Furthermore, it was found that the sensitivity of the nanotube transducer depended on the degree of the carboxylic group introduced. Finally, a sensor array composed of 5 different transducers including the carboxylated nanotubes exhibited excellent selectivity to DMMP in 16 vapor species.

  2. Carboxylic Acid-Functionalized Conducting-Polymer Nanotubes as Highly Sensitive Nerve-Agent Chemiresistors

    PubMed Central

    Kwon, Oh Seok; Park, Chul Soon; Park, Seon Joo; Noh, Seonmyeong; Kim, Saerona; Kong, Hye Jeong; Bae, Joonwon; Lee, Chang-Soo; Yoon, Hyeonseok

    2016-01-01

    Organophosphates are powerful inhibitors of acetylcholinesterase, which is critical to nerve function. Despite continuous research for detecting the highly toxic organophosphates, a new and improved methodology is still needed. Herein we demonstrate simple-to-fabricate chemiresistive gas sensors using conducting-polymer polypyrrole (PPy) nanotube transducers, which are chemically specific and capable of recognizing sub-ppb concentrations (ca. 0.5 ppb) of dimethyl methylphosphonate (DMMP), a simulant of nerve agent sarin. Interestingly, the introduction of carboxylic groups on the surface of PPy nanotube transistors resulted in enhanced sensitivity to DMMP via intermolecular hydrogen bonding. Furthermore, it was found that the sensitivity of the nanotube transducer depended on the degree of the carboxylic group introduced. Finally, a sensor array composed of 5 different transducers including the carboxylated nanotubes exhibited excellent selectivity to DMMP in 16 vapor species. PMID:27650635

  3. Selection of a biocontrol agent based on a potential mechanism of action: degradation of nicotinic acid, a growth factor essential for Erwinia amylovora.

    PubMed

    Paternoster, Thomas; Défago, Geneviève; Duffy, Brion; Gessler, Cesare; Pertot, Ilaria

    2010-12-01

    This work describes a medium-based screening method for selecting microbial biocontrol agents against Erwinia amylovora based on the degradation of a specific growth factor. Erwinia amylovora, the causal agent of the devastating fire blight disease, requires nicotinic acid or nicotinamide as an essential growth factor. Potential biocontrol agents are either selected for antimicrobial production in plate or directly on immature pears or apple blossoms. In this work, we have attempted to streamline the selection of a new potential biocontrol agent with a lower risk of non-target effects by isolation based on the ability to degrade nicotinic acid in vitro, using therefore few plant materials. A total of 735 bacteria and 1237 yeast were isolated from apple blossoms and pre-screened for nicotinic acid-degradation. Pseudomonas rhizosphaerae strain JAN was able to degrade both nicotinic acid and nicotinamide. Mutants deficient in this ability were constructed. JAN, but not the mutants, controlled E. amylovora on pear slices. On detached apple blossoms, JAN colonized apple hypanthia and strongly suppressed E. amylovora growth. Under greenhouse conditions, JAN was more effective in controlling blossom blight than P. fluorescens A506, a commercial biocontrol agent of fire blight unable to degrade nicotinic acid and nicotinamide.

  4. α-Linolenic acid (ALA) is an anti-inflammatory agent in inflammatory bowel disease.

    PubMed

    Reifen, Ram; Karlinsky, Anna; Stark, Aliza H; Berkovich, Zipi; Nyska, Abraham

    2015-12-01

    Studies suggest that consumption of omega-3 (n-3) polyunsaturated fatty acids (PUFA) plays a protective role in inflammatory bowel disease; however, the use of plant-derived oils rich in α-linolenic acid (ALA) has not been widely investigated. The aims of this study were to test the effects of two different sources of (n-3) PUFA, fish and plant-derived oils, in two animal models of experimental colitis and to determine whether the (n-3) PUFA-enriched diets could ameliorate the inflammatory status. Rats were fed diets rich in corn, fish or sage oil with or without vitamin A supplementation for 3weeks then colitis was induced by adding dextran sodium sulfate to the drinking water or by injecting 2,4,6-trinitrobenzene sulfonic acid. We show that colitic rats fed the sage oil diets had a lower inflammatory response, improved histological repair and had less necrotic damage in the mucosa when compared to the corn and fish oil groups. Colonic damage and myeloperoxidase activity were significantly lower. Colonic mRNA levels of pro-inflammatory genes including interleukin IL-6, cyclooxygenase 2 and tumor necrosis factor α were markedly down-regulated in rats fed fish and sage oils compared to control. These results were supported by experiments in the human colonic epithelial cell line Caco-2, where ALA supplementation was shown to be effective in inhibiting inflammation induced by IL-1β by down-regulating mRNA levels of pro-inflammatory genes including IL-8, COX2 and inducible nitric oxide synthase. Taken together, these results suggest that plant-derived oil rich in ALA could ameliorate the inflammatory damage in colitis.

  5. Synthesis of Amino Derivatives of Dithio Acids as Potential Radiation Protective Agents

    DTIC Science & Technology

    1983-08-01

    William 0. Foye , Ph.D. ZLECTE :’W2 August 1983 Supported by U.S. ARMY MEDICAL RESEARCH AND DEVELOPMENT COMMAND Fort Detrick, Frederick, Maryland 21701-5012...3 ŗ II 4if -2- Table I. Ccmpounds Submitted for Screening i Code No. 0942 Compound Structure Wt.g. Reference 1,6-Dimethylquinolinium-2- I 2.2 Foye ...et.al., J. Pharm. Sci. I dithioacetic acid zwitterion 67, 962 (1978) 1 -Methyl-2-bis(2-methylthio)- II 3.1 Foye and Kauffman, ibid., vinylquinolinium

  6. Design, synthesis and evaluation of PEGylated lipoic acid derivatives with functionality as potent anti-melanogenic agents.

    PubMed

    Lu, Chichong; Kim, Bo-Mi; Chai, Kyu Yun

    2011-10-01

    The novel PEGylated lipoic acid (LA) derivatives with functionality were synthesized in satisfactory yield by simple procedures and evaluated about its anti-melanogenic activity on the B16F10 melanoma cells. Grafting a PEG moiety onto the carboxyl group of LA has reduced the cell cytotoxicity and provided the water solubility and functionality to incorporate the other bioactive moieties. We have found that derivatives showed inhibition of melanin formation by up to 36.5% at 0.1 mM, whereas LA decreased the melanin formation by 8.6%. In addition, it also inhibits at least 86.4% UV-induced MMP-1 expression at 0.1 mM which is higher than LA. These data suggest that the novel PEGylated LA derivatives with functionality may thus serve as a potentially effective anti-melanogenic and anti-aging agent.

  7. [Determination of antidangdruff agent salicylic acid, zinc pyrithione, octopirox, climbazole and ketoconazole in shampoo by high performance liquid chromatography].

    PubMed

    Yang, Yan-Wei; Zhu, Ying; Su, Xiao-Qing

    2005-09-01

    A high performance liquid chromatography method was established for determination of antidangdruff agent salicylic acid,zinc pyrithione, octopirox, climbazole and ketoconazole in shampoo on a C18 column using acetonitrile-metholaqueous solution (10 mmol/L KH2 PO4 and 5 mmol/L EDTANa2, pH is adjusted to 4.0 with H3 PO4) (50:10:40) as mobile phase at a flow rate of 1.0 ml/min, with the column temperature 25 degrees C and detection wave 230nm. The precision was less than 3.8% and recovery varied from 92.7% to 104.9%. The experimental results showed that the method was simple, precise and accurate.

  8. The sensitization of near-ultraviolet radiation killing of mammalian cells by the sunscreen agent para-aminobenzoic acid

    SciTech Connect

    Osgood, P.J.; Moss, S.H.; Davies, D.J.

    1982-12-01

    The wavelengths of sunlight considered to be responsible for erythema and skin cancer formation are in the range 290-340 nm. Formulated sunscreens usually contain an agent that absorbs in this wavelength region, and one of the most widely used is para-aminobenzoic acid (PABA). Previous work has demonstrated the sensitization by PABA of the lethal and mutagenic effects of near-ultraviolet (UV) radiation in a model bacterial system. Experiments with the mouse lymphoma L5178Y cell line have now demonstrated sensitization by PABA of the lethal effect of near-UV radiation, the extent of which, after correction for absorption of UV radiation by PABA, bears a direct relationship to PABA concentration. The limitations of these results in predicting the response of human skin to the presence of PABA during exposure to UV radiation is emphasized.

  9. “On-Off” Thermoresponsive Coating Agent Containing Salicylic Acid Applied to Maize Seeds for Chilling Tolerance

    PubMed Central

    He, Fei; Huang, Yutao; Song, Wenjian; Hu, Jin

    2015-01-01

    Chilling stress is an important constraint for maize seed establishment in the field. In this study, a type of “on-off” thermoresponsive coating agent containing poly (N-isopropylacrylamide-co-butylmethacrylate) (Abbr. P(NIPAm-co-BMA)) hydrogel was developed to improve the chilling tolerance of coated maize seed. The P(NIPAm-co-BMA) hydrogel was synthesized by free-radical polymerization of N-isopropylacrylamide (NIPAm) and butylmethacrylate (BMA). Salicylic acid (SA) was loaded in the hydrogel as the chilling resistance agent. SA-loaded P(NIPAm-co-BMA) was used for seed film-coating of two maize varieties, Huang C (HC, chilling-tolerant) and Mo17 (chilling-sensitive), to investigate the coated seed germination and seedling growth status under chilling stress. The results showed that the hydrogel obtained a phase transition temperature near 12°C with a NIPAM to MBA weight ratio of 1: 0.1988 (w/w). The temperature of 12°C was considered the “on-off” temperature for chilling-resistant agent release; the SA was released from the hydrogel more rapidly at external temperatures below 12°C than above 12°C. In addition, when seedlings of both maize varieties suffered a short chilling stress (5°C), higher concentrations of SA-loaded hydrogel resulted in increased germination energy, germination percentage, germination index, root length, shoot height, dry weight of roots and shoots and protective enzyme activities and a decreased malondialdehyde content in coated maize seeds compared to single SA treatments. The majority of these physiological and biochemical parameters achieved significant levels compared with the control. Therefore, SA-loaded P(NIPAm-co-BMA), a nontoxic thermoresponsive hydrogel, can be used as an effective material for chilling tolerance in film-coated maize seeds. PMID:25807522

  10. Screening of nerve agent markers with hollow fiber-chemosorption of phosphonic acids.

    PubMed

    Holmgren, Karin Höjer; Gustafsson, Tomas; Östin, Anders

    2016-10-15

    This report describes a method developed for extracting nerve gas markers such as phosphonic acids from urine and other aqueous samples. It involves single-step microextraction with chemosorption to hollow fibers that have been pre-soaked in a solution containing a derivatization reagent (3,5 triflouro methyl benzene diazomethane). The derivatives it forms with phosphonic acids can be sensitively detected by mass spectrometric detectors operating in negative chemical ionization (NCI) mode. Limits of quantification obtained in analyses of water and urine extracts by GC/MS in negative chemical ionization and selected ion monitoring mode were 0.1-10 and 0.5-10ng/mL, respectively. Pentaflourophenyl diazomethane can also be used as a derivatization reagent, and the micro-extracts (which generate low background signals) can be sensitively analyzed by GC-MS/MS in NCI selected reaction monitoring (SRM) mode, using two specific transitions for both reagents. Thus, this sensitive approach can be flexibly modified to obtain confirmatory information, or address potential problems caused by interferences in some samples.

  11. Radiolabelling of ascorbic acid: a new clue to clarify its action as an anticancer agent?

    PubMed

    Mamede, A C; Abrantes, A M; Pires, A S; Tavares, S D; Serra, M E; Maia, J M; Botelho, M F

    2012-04-01

    Vitamin C exists in two forms: the reduced (ascorbic acid--AA) and oxidized form (dehydroascorbic acid--DHA). This is a nutrient whose benefits are long known and widely publicized, being most of them related to its antioxidant action. As an antioxidant, the main role of vitamin C is to neutralize free radicals, reducing oxidative stress. However, some controversial studies suggest that this nutrient may have a preventive and therapeutic role in cancer disease due to their possible pro-oxidant activity, promoting the formation of reactive oxygen species that can induce cell death in cancer cells. This factor, coupled with the decrease of antioxidant enzymes and increase of decompartmentalized transition metals in tumor cells may result in the selective cytotoxicity of vitamin C and the subsequent revelation of its therapeutic potential. In this way the first purpose of this work was radioactively label the reduced form of vitamin C with Tc-99m, its quality control by HPLC and the time stability. The second purpose was to use the radioactive complex 99mTc-AA in in vitro and in vivo studies in order to evaluate its uptake by colorectal cancer cells and biodistribution in mices, respectively. The results suggest that the pharmaceutical formulation developed, which was reproducible and stable over time, was residually taken up by colorectal cancer cells. Future studies are needed to deepen our understanding about the radioactive complex 99mTc-AA and clarify the mechanisms of action of vitamin C in oncologic disease.

  12. The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer

    PubMed Central

    Sadowski, Martin C.; Pouwer, Rebecca H.; Gunter, Jennifer H.; Lubik, Amy A.; Quinn, Ronald J.; Nelson, Colleen C.

    2014-01-01

    Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer. PMID:25313139

  13. Benzothiopyranoindole-based antiproliferative agents: synthesis, cytotoxicity, nucleic acids interaction, and topoisomerases inhibition properties.

    PubMed

    Dalla Via, Lisa; Magno, Sebastiano Marciani; Gia, Ornella; Marini, Anna Maria; Da Settimo, Federico; Salerno, Silvia; La Motta, Concettina; Simorini, Francesca; Taliani, Sabrina; Lavecchia, Antonio; Di Giovanni, Carmen; Brancato, Giuseppe; Barone, Vincenzo; Novellino, Ettore

    2009-09-10

    Novel benzo[3',2':5,6]thiopyrano[3,2-b]indol-10(11H)-ones 1a-v were synthesized and evaluated for their antiproliferative activity in an in vitro assay of human tumor cell lines (HL-60 and HeLa). Compounds 1e-v, substituted at the 11-position with a basic side chain, showed a significant ability to inhibit cell growth with IC(50) values in the low micromolar range. Linear dichroism measurements showed that all 11-dialkylaminoalkyl substituted derivatives 1e-v behave as DNA-intercalating agents. Fluorimetric titrations demonstrated their specificity in binding to A-T rich regions, and molecular modeling studies were performed on the most active derivatives (1e, 1i, 1p) to characterize in detail the complexation mechanism of these benzothiopyranoindoles to DNA. A relaxation assay evidenced a dose-dependent inhibition of topoisomerase II activity that appeared in accordance with the antiproliferative capacity. Finally, for the most cytotoxic derivative, 1e, a topoisomerase II poisoning effect was also demonstrated, along with a weak inhibition of topoisomerase I-mediated relaxation.

  14. The fatty acid synthase inhibitor triclosan: repurposing an anti-microbial agent for targeting prostate cancer.

    PubMed

    Sadowski, Martin C; Pouwer, Rebecca H; Gunter, Jennifer H; Lubik, Amy A; Quinn, Ronald J; Nelson, Colleen C

    2014-10-15

    Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer.

  15. Synthesis of conjugated bile acids/azastilbenes as potential antioxidant and photoprotective agents.

    PubMed

    dos Santos, Juliana Alves; Polonini, Hudson Caetano; Suzuki, Érika Yoko; Raposo, Nádia R B; da Silva, Adilson David

    2015-06-01

    A series of 14 bile acids/azastilbenes conjugates (1a-g and 2a-g) was prepared through the condensation of bile amides (1 and 2) and aromatic aldehydes. The newly synthesized conjugates were evaluated in vitro for their antioxidant and photoprotective activities. Six compounds (1, 1a, 1b, 2, 2a and 2b) showed promising antioxidant activity with IC50 values of 19.60-31.83 μg mL(-1). The synthesized compounds presented a varied photoprotection profile, with the SPF ranging from 2 to 9. Among the 16 compounds tested for the protection against UVB sunrays, 3 compounds (2c, 2e and 2g) presented more significant protection than resveratrol and the free azastilbene 3; while the UVAPF increased from 2 in resveratrol and 5 in 3 to 5-11 in the majority of the conjugates.

  16. Design and synthesis of gambogic acid analogs as potent cytotoxic and anti-inflammatory agents

    PubMed Central

    Yen, Chiao-Ting; Nakagawa-Goto, Kyoko; Hwang, Tsong-Long; Morris-Natschke, Susan L.; Bastow, Kenneth F.; Wu, Yang-Chang; Lee, Kuo-Hsiung

    2012-01-01

    Prenyl- and pyrano-xanthones derived from 1,3,6-trihydroxy-9H-xanthen-9-one, a basic backbone of gambogic acid (GA), were synthesized and evaluated for in vitro cytotoxic effects against four human cancer cell lines (KB, KBvin, A549, and DU-145) and anti-inflammatory activity toward superoxide anion generation and elastase release by human neutrophils in response to fMLP/CB. Among them, prenylxanthones 7-13 were generally less active than pyranoxanthones 14-21 in both anticancer and anti-inflammatory assays. Furthermore, two angular 3,3-dimethypyranoxanthones (16 and 20) showed the greatest and selective activity against the KBvin multidrug resistant (MDR) cell line with IC50 values of 0.9 and 0.8 μ g/mL, respectively. An angular 3-methyl-3-prenylpyranoxanthone (17) selectively inhibited elastase release with 200 times more potency than phenylmethylsulfonyl fluoride (PMSF), the positive control. PMID:22595179

  17. Oleic Acid Produced by a Marine Vibrio spp. Acts as an Anti-Vibrio parahaemolyticus Agent

    PubMed Central

    Leyton, Yanett; Borquez, Jorge; Darias, José; Cueto, Mercedes; Díaz-Marrero, Ana R.; Riquelme, Carlos

    2011-01-01

    It is known that some strains of Vibrio parahaemolyticus are responsible for gastroenteric diseases caused by the ingestion of marine organisms contaminated with these bacterial strains. Organic products that show inhibitory activity on the growth of the pathogenic V. parahaemolyticus were extracted from a Vibrio native in the north of Chile. The inhibitory organic products were isolated by reverse phase chromatography and permeation by Sephadex LH20, and were characterized by spectroscopic and spectrometric techniques. The results showed that the prevailing active product is oleic acid, which was compared with standards by gas chromatography and high-performance liquid chromatography (HPLC). These active products might be useful for controlling the proliferation of pathogenic clones of V. parahaemolyticus. PMID:22073014

  18. Synthesis, evaluation and molecular docking studies of amino acid derived N-glycoconjugates as antibacterial agents.

    PubMed

    Baig, Noorullah; Singh, Rajnish Prakash; Chander, Subhash; Jha, Prabhat Nath; Murugesan, Sankaranarayanan; Sah, Ajay K

    2015-12-01

    Six amino acid derived N-glycoconjugates of d-glucose were synthesized, characterized and tested for antibacterial activity against G(+)ve (Bacillus cereus) as well as G(-)ve (Escherichia coli and Klebsiella pneumoniae) bacterial strains. All the tested compounds exhibited moderate to good antibacterial activity against these bacterial strains. The results were compared with the antibacterial activity of standard drug Chloramphenicol, where results of A5 (Tryptophan derived glycoconjugates) against E. coli and A4 (Isoleucine derived glycoconjugates) against K. pneumoniae bacterial strains are comparable with the standard drug molecule. In silico docking studies were also performed in order to understand the mode of action and binding interactions of these molecules. The docking studies revealed that, occupation of compound A5 at the ATP binding site of subunit GyrB (DNA gyrase, PDB ID: 3TTZ) via hydrophobic and hydrogen bonding interactions may be the reason for its significant in vitro antibacterial activity.

  19. Synthesis and biological evaluation of strained unusual amino acid containing tetrapeptides as potential antidepressant agents.

    PubMed

    Mainkar, Prathama S; Chakravarty, Sumana; Srujana, Takkallapally; Vishwanathan, Libi Anandi; Prajapti, Santosh Kumar; Chandra, Karisetty Bhanu; Veeraval, Lenin; Babu, Bathini Nagendra

    2015-12-01

    Strained unusual amino acid derived tetrapeptides were synthesized as mimics of GLYX-13, a clinical candidate for neuroprotective and anti-depressant properties, were studied. The synthesized compounds were screened for neurite growth and anti-depressant properties in vitro and in vivo respectively comparing with the parent GLYX-13 compound. Neurite growth property was assessed by neurite length and anti-depressant property by percentage of immobility in forced swim test, a behavioural assay. Mechanistic insights about protein-ligand interactions were obtained using molecular docking study. Based on the in vitro and in vivo screening data and molecular docking study, a new analogue of GLYX-13, Compound 11a has been found to be as good as the parent compound in all respects.

  20. Acridone acetic acid, sodium salt, as an agent to stop vitiligo progression: a pilot study.

    PubMed

    Korobko, Igor V; Lomonosov, Konstantin M

    2014-01-01

    Vitiligo progression is attributed to immune system malfunctioning, thus immunomodulating compounds might be beneficial in stopping vitiligo progression which is a prerequisite for successful repigmentation. The goal of this study was to assess efficacy of acridone acetic acid, sodium salt (Na-AAA), an immunomodulating compound with favorable safety profile, in stabilizing active vitiligo, and to reveal prognostic factors of treatment outcome. Sixty consecutive patients with progressing nonsegmental vitiligo were treated with 10 i.m. injections of Na-AAA every other day. Disease stability was assessed in 1, 3, 6, and 12 months post-treatment. Statistical analysis was applied to correlate treatment outcome and available clinical parameters. Of the 60 patients treated, vitiligo stopped progression in 44 patients (73.3%). Older age (p = 0.0219), age of 35 and older (p = 0.0189, odds ratio (OR) = 5.2, 95% confidence interval (CI) 1.30-20.84) or age of 40 and older (p = 0.0039, OR = 6.48, 95% CI 1.86-22.61), longer disease duration (p = 0.0234), pre-treatment interleukin-6 level over 2 pg/mL (p = 0.0005, OR = 13.7, 95% CI 2.97-63), and over the reference threshold value 5.9 pg/mL (p = 0.0009, OR = 25.8, 95% CI 2.8-239) as well as presence of other autoimmune diseases (p = 0.038, OR = 7.0, 95% CI 1.14-42.97) were negative prognostic factors of treatment success. In conclusion, acridone acetic acid, sodium salt, emerges as an efficient option for stopping vitiligo progression.

  1. Influence of pH, bleaching agents, and acid etching on surface wear of bovine enamel

    PubMed Central

    Soares, Ana Flávia; Bombonatti, Juliana Fraga Soares; Alencar, Marina Studart; Consolmagno, Elaine Cristina; Honório, Heitor Marques; Mondelli, Rafael Francisco Lia

    2016-01-01

    ABSTRACT Development of new materials for tooth bleaching justifies the need for studies to evaluate the changes in the enamel surface caused by different bleaching protocols. Objective The aim of this study was to evaluate the bovine dental enamel wear in function of different bleaching gel protocols, acid etching and pH variation. Material and Methods Sixty fragments of bovine teeth were cut, obtaining a control and test areas. In the test area, one half received etching followed by a bleaching gel application, and the other half, only the bleaching gel. The fragments were randomly divided into six groups (n=10), each one received one bleaching session with five hydrogen peroxide gel applications of 8 min, activated with hybrid light, diode laser/blue LED (HL) or diode laser/violet LED (VHL) (experimental): Control (C); 35% Total Blanc Office (TBO35HL); 35% Lase Peroxide Sensy (LPS35HL); 25% Lase Peroxide Sensy II (LPS25HL); 15% Lase Peroxide Lite (LPL15HL); and 10% hydrogen peroxide (experimental) (EXP10VHL). pH values were determined by a pHmeter at the initial and final time periods. Specimens were stored, subjected to simulated brushing cycles, and the superficial wear was determined (μm). ANOVA and Tukey´s tests were applied (α=0.05). Results The pH showed a slight decrease, except for Group LPL15HL. Group LPS25HL showed the highest degree of wear, with and without etching. Conclusion There was a decrease from the initial to the final pH. Different bleaching gels were able to increase the surface wear values after simulated brushing. Acid etching before bleaching increased surface wear values in all groups. PMID:27008254

  2. Biodegradable and non-retrogradable eco-films based on starch-glycerol with citric acid as crosslinking agent.

    PubMed

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

    2016-03-15

    Biodegradable and non-retrogradable starch-glycerol based films were obtained using citric acid (CA) as crosslinking agent at 75°C. This material allowed decreasing water vapor permeability (WVP) more than 35%, remained amorphous for at least 45 days as a result of the network formed by the CA that avoided starch retrogradation and maintained the degradability in compost, occurring only six days after the films without citric acid. A simulation of the gelatinization process of starch-glycerol with and without CA, using a differential thermal analysis device, showed that the system with CA completed the gelatinization 5°C before than the other and, CA first reacted with glycerol and then starch-glycerol-CA reaction occurred. The temperature at which the gelatinization process was carried out was critical to obtain the best results. An increase of gelatinization process temperature at 85°C in system with CA, led to a worsening on WVP and its integrity after a swelling process with dimethylsulphoxide (DMSO), compared to the films processed at 75°C.

  3. Versatile methods for synthesizing organic acid salts of quaternary berberine-type alkaloids as anti-ulcerative colitis agents.

    PubMed

    Zhang, Zhi-Hui; Li, Jing; Zhang, Hai-Jing; Deng, An-Jun; Wu, Lian-Qiu; Li, Zhi-Hong; Song, Hong-Rui; Wang, Wen-Jie; Qin, Hai-Lin

    2016-06-01

    Two versatile methods to synthesize kinds of organic acid salts of quaternary berberine-type alkaloids were investigated in order to determine which is more efficient to improve the liposolubility of the target compounds and to explore the efficacy of the target compounds as anti-ulcerative colitis (UC) agents. Overall evaluation according to the reaction results and yields of the final products indicated that the synthetic method using tertiary (±)-8-acylmethyldihydroberberine-type alkaloids as key intermediates is superior to that of using tertiary dihydroberberine-type alkaloids as intermediates. Ten target compounds were synthesized using quaternary berberine chloride and quaternary coptisine chloride as starting materials, respectively, and the anti-UC activity of some target compounds was evaluated in an in vitro x-box-binding protein 1 (XBP1) transcriptional activity assay using dual luciferase reporter detection. At 10 μM, the tested compounds were found to activate the transcription of XBP1 target at almost the same level as that of quaternary coptisine chloride. The synthesized target compounds were also found to share higher liposolubility than the inorganic acid salts of quaternary berberine-type alkaloid.

  4. Biocontrol agents-mediated suppression of oxalic acid induced cell death during Sclerotinia sclerotiorum-pea interaction.

    PubMed

    Jain, Akansha; Singh, Akanksha; Singh, Surendra; Sarma, Birinchi Kumar; Singh, Harikesh Bahadur

    2015-05-01

    Oxalic acid (OA) is an important pathogenic factor during early Sclerotinia sclerotiorum-host interaction and might work by reducing hydrogen peroxide production (H2 O2 ). In the present investigation, oxalic acid-induced cell death in pea was studied. Pea plants treated with biocontrol agents (BCAs) viz., Pseudomonas aeruginosa PJHU15, Bacillus subtilis BHHU100, and Trichoderma harzianum TNHU27 either singly and/or in consortium acted on S. sclerotiorum indirectly by enabling plants to inhibit the OA-mediated suppression of oxidative burst via induction of H2 O2 . Our results showed that BCA treated plants upon treatment with culture filtrate of the pathogen, conferred the resistance via. significantly decreasing relative cell death of pea against S. sclerotiorum compared to control plants without BCA treatment but treated with the culture filtrate of the pathogen. The results obtained from the present study indicate that the microbes especially in consortia play significant role in protection against S. sclerotiorum by modulating oxidative burst and partially enhancing tolerance by increasing the H2 O2 generation, which is otherwise suppressed by OA produced by the pathogen.

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

    PubMed

    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.

  6. Hemolysis of human erythrocytes by hypochlorous acid is modulated by amino acids, antioxidants, oxidants, membrane-perforating agents and by divalent metals.

    PubMed

    Ginsburg, Isaac; Sadovnic, Milu; Yedgar, Shaul; Kohen, Ron; Hrbac, Jan

    2002-06-01

    The optimal conditions under which hypochlorous acid (NaOCl) either hemolyzes human RBC or kills monkey kidney epithelial cells (BGM) in culture had been investigated. While in Hank's balanced salt solution (HBSS), micromolar amounts of NaOCl caused full hemolysis and also killed BGM cells, in D-MEM or RPMI media rich in amino acids, 25-40 mM of hypochlorite were needed to induce cell injury. Cells exposed to high amounts of NaOCl became highly refractory to strong detergents. Hemolysis by NaOCl was strongly inhibited by a large variety of antioxidants. RBC treated by subtoxic concentrations either of peroxide, peroxyl radical, NO, cholesterol, PLA2, PLC as well as by N2, argon or by mixture of CO2 (10%) and O2 (90%) became much more susceptible to lysis by NaOCl. On the other hand, while RBC treated by Fe2+, Co2+, and V2+ and to a lesser extent with Cu2+ became highly resistant to NaOCl hemolysis presumably due to NaOCl decomposition, no such effect was found either with Co2+ or by Mn2+. RBC treated by azide to destroy catalase and then incubated with peroxide and with NaOCl failed to undergo hemolysis due to the ability of peroxide to decompose NaOCl. The inhibitory effects of the divalent metals on NaOCl-induced hemolysis were also substantiated by measuring the decrease in pH and by cyclic voltammetry. The findings that like peroxide, NaOCl also synergizes with membrane-perforating agents and with a protease to kill epithelial cells further implicate such "cocktails" in cell injury in inflammatory conditions. Taken together, because of the capacity of many agents to scavenge NaOCl, tissue damage by NaOCl-generated neutrophils can take place primarily if activated neutrophils closely adhere to target cells to avoid the scavenging effects of amino acids and of antioxidants. Therefore, the significance of the data which had tested the cytotoxic effects of NaOCl using cells suspended only in salt solutions, should be reconsidered.

  7. Development of antiproliferative nanohybrid compound with controlled release property using ellagic acid as the active agent

    PubMed Central

    Hussein, Mohd Zobir; Al Ali, Samer Hasan; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2011-01-01

    An ellagic acid (EA)–zinc layered hydroxide (ZLH) nanohybrid (EAN) was synthesized under a nonaqueous environment using EA and zinc oxide (ZnO) as the precursors. Powder X-ray diffraction showed that the basal spacing of the nanohybrid was 10.4 Å, resulting in the spatial orientation of EA molecules between the interlayers of 22.5° from z-axis with two negative charges at 8,8′ position of the molecules pointed toward the ZLH interlayers. FTIR study showed that the intercalated EA spectral feature is generally similar to that of EA, but with bands slightly shifted. This indicates that some chemical bonding of EA presence between the nanohybrid interlayers was slightly changed, due to the formation of host–guest interaction. The nanohybrid is of mesopores type with 58.8% drug loading and enhanced thermal stability. The release of the drug active, EA from the nanohybrid was found to be sustained and therefore has good potential to be used as a drug controlled-release formulation. In vitro bioassay study showed that the EAN has a mild effect on the hepatocytes cells, similar to its counterpart, free EA. PMID:21796241

  8. (-)-UB006: A new fatty acid synthase inhibitor and cytotoxic agent without anorexic side effects.

    PubMed

    Makowski, Kamil; Mir, Joan Francesc; Mera, Paula; Ariza, Xavier; Asins, Guillermina; Hegardt, Fausto G; Herrero, Laura; García, Jordi; Serra, Dolors

    2017-05-05

    C75 is a synthetic anticancer drug that inhibits fatty acid synthase (FAS) and shows a potent anorexigenic side effect. In order to find new cytotoxic compounds that do not impact food intake, we synthesized a new family of C75 derivatives. The most promising anticancer compound among them was UB006 ((4SR,5SR)-4-(hydroxymethyl)-3-methylene-5-octyldihydrofuran-2(3H)-one). The effects of this compound on cytotoxicity, food intake and body weight were studied in UB006 racemic mixture and in both its enantiomers separately. The results showed that both enantiomers inhibit FAS activity and have potent cytotoxic effects in several tumour cell lines, such as the ovarian cell cancer line OVCAR-3. The (-)-UB006 enantiomer's cytotoxic effect on OVCAR-3 was 40-fold higher than that of racemic C75, and 2- and 38-fold higher than that of the racemic mixture and its opposite enantiomer, respectively. This cytotoxic effect on the OVCAR-3 cell line involves mechanisms that reduce mitochondrial respiratory capacity and ATP production, DDIT4/REDD1 upregulation, mTOR activity inhibition, and caspase-3 activation, resulting in apoptosis. In addition, central and peripheral administration of (+)-UB006 or (-)-UB006 into rats and mice did not affect food intake or body weight. Altogether, our data support the discovery of a new potential anticancer compound (-)-UB006 that has no anorexigenic side effects.

  9. Peracetic acid: a practical agent for sterilizing heat-labile polymeric tissue-engineering scaffolds.

    PubMed

    Yoganarasimha, Suyog; Trahan, William R; Best, Al M; Bowlin, Gary L; Kitten, Todd O; Moon, Peter C; Madurantakam, Parthasarathy A

    2014-09-01

    Advanced biomaterials and sophisticated processing technologies aim at fabricating tissue-engineering scaffolds that can predictably interact within a biological environment at the cellular level. Sterilization of such scaffolds is at the core of patient safety and is an important regulatory issue that needs to be addressed before clinical translation. In addition, it is crucial that meticulously engineered micro- and nano- structures are preserved after sterilization. Conventional sterilization methods involving heat, steam, and radiation are not compatible with engineered polymeric systems because of scaffold degradation and loss of architecture. Using electrospun scaffolds made from polycaprolactone, a low melting polymer, and employing spores of Bacillus atrophaeus as biological indicators, we compared ethylene oxide, autoclaving and 80% ethanol to a known chemical sterilant, peracetic acid (PAA), for their ability to sterilize as well as their effects on scaffold properties. PAA diluted in 20% ethanol to 1000 ppm or above sterilized electrospun scaffolds in 15 min at room temperature while maintaining nano-architecture and mechanical properties. Scaffolds treated with PAA at 5000 ppm were rendered hydrophilic, with contact angles reduced to 0°. Therefore, PAA can provide economical, rapid, and effective sterilization of heat-sensitive polymeric electrospun scaffolds that are used in tissue engineering.

  10. Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer

    PubMed Central

    Kuo, Ying-Yu; Jim, Wai-Tim; Su, Liang-Cheng; Chung, Chi-Jung; Lin, Ching-Yu; Huo, Chieh; Tseng, Jen-Chih; Huang, Shih-Han; Lai, Chih-Jen; Chen, Bo-Chih; Wang, Bi-Juan; Chan, Tzu-Min; Lin, Hui-Ping; Chang, Wun-Shaing Wayne; Chang, Chuang-Rung; Chuu, Chih-Pin

    2015-01-01

    Head and neck cancers, which affect 650,000 people and cause 350,000 deaths per year, is the sixth leading cancer by cancer incidence and eighth by cancer-related death worldwide. Oral cancer is the most common type of head and neck cancer. More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs. In this review we discuss the possibility of using caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells. CAPE treatment inhibits Akt signaling, cell cycle regulatory proteins, NF-κB function, as well as activity of matrix metalloproteinase (MMPs), epidermal growth factor receptor (EGFR), and Cyclooxygenase-2 (COX-2). Therefore, CAPE treatment induces cell cycle arrest and apoptosis in oral cancer cells. According to the evidence that aberrations in the EGFR/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling, NF-κB function, COX-2 activity, and MMPs activity are frequently found in oral cancers, and that the phosphorylation of Akt, EGFR, and COX-2 correlates to oral cancer patient survival and clinical progression, we believe that CAPE treatment will be useful for treatment of advanced oral cancer patients. PMID:25984601

  11. Synthesis and Evaluation of Novel Triterpene Analogues of Ursolic Acid as Potential Antidiabetic Agent

    PubMed Central

    Wu, Panpan; Zheng, Jie; Huang, Tianming; Li, Dianmeng; Hu, Qingqing; Cheng, Anming; Jiang, Zhengyun; Jiao, Luoying; Zhao, Suqing; Zhang, Kun

    2015-01-01

    Ursolic acid (UA) is a naturally bioactive compound that possesses potential anti-diabetic activity. The relatively safe and effective molecule intrigued us to further explore and to improve its anti-diabetic activity. In the present study, a series of novel UA analogues was synthesized and their structures were characterized. Their bioactivities against the α-glucosidase from baker's yeast were determined in vitro. The results suggested that most of the analogues exhibited significant inhibitory activity, especially analogues 8b and 9b with the IC50 values of 1.27 ± 0.27 μM (8b) and 1.28 ± 0.27 μM (9b), which were lower than the other analogues and the positive control. The molecular docking and 2D-QSAR studies were carried out to prove that the C-3 hydroxyl could interact with the hydrophobic region of the active pocket and form hydrogen bonds to increase the binding affinity of ligand and the homology modelling protein. Thus, these results will be helpful for understanding the relationship between binding mode and bioactivity and for designing better inhibitors from UA analogues. PMID:26406581

  12. Preliminary Appraisal of Ferrocene as an Igniting Agent for JP-4 Fuel and Fuming Nitric Acid

    NASA Technical Reports Server (NTRS)

    Miller, RIley O.

    1953-01-01

    A preliminary experimental study was made of the properties of ferrocene as a solute and as a suspension in JP-4 fuel, and of the ignition delays of ferrocene - JP-4 mixture with A.F. specification 14104 white fuming nitric acid (WFNA). The investigation covered concentrations of 4 to 10 percent by weight ferrocene, and a temperature range of -40 to 80 F. The solubility of ferrocene in JP-4 is about 5 percent at room temperature and about 1 percent (extrapolated) at -80 F. The solubility is increased somewhat by increased aromatics content. Undissolved ferrocene particles of 100 mesh and smaller settle rapidly in JP-4. Clear solutions of 4 and 5 percent ferrocene in JP-4 fuels containing 10 and 25 percent by volume aromatics, respectively, do not ignite with WFNA at room temperature. Mixtures containing 10 percent ferrocene (100- mesh and smaller undissolved particles in suspension) ignited with vigorous persistent flames at room temperature, but did not ignite at -38 F. The ignition delays at room temperature, however, were widely varied; the range from 85 milliseconds to over 1 second perhaps reflected differences in degree of sedimentation.

  13. Oleanolic acid (OA) as an antileishmanial agent: Biological evaluation and in silico mechanistic insights.

    PubMed

    Melo, Tahira Souza; Gattass, Cerli Rocha; Soares, Deivid Costa; Cunha, Micael Rodrigues; Ferreira, Christian; Tavares, Maurício Temotheo; Saraiva, Elvira; Parise-Filho, Roberto; Braden, Hannah; Delorenzi, Jan Carlo

    2016-06-01

    Although a worldwide health problem, leishmaniasis is considered a highly neglected disease, lacking efficient and low toxic treatment. The efforts for new drug development are based on alternatives such as new uses for well-known drugs, in silico and synthetic studies and naturally derived compounds. Oleanolic acid (OA) is a pentacyclic triterpenoid widely distributed throughout the Plantae kingdom that displays several pharmacological activities. OA showed potent leishmancidal effects in different Leishmania species, both against promastigotes (IC(50 L. braziliensis) 30.47 ± 6.35 μM; IC(50 L. amazonensis) 40.46 ± 14.21 μM; IC(50 L. infantum) 65.93 ± 15.12 μM) and amastigotes (IC(50 L. braziliensis) 68.75 ± 16.55 μM; IC(50 L. amazonensis) 38.45 ± 12.05 μM; IC(50 L. infantum) 64.08 ± 23.52 μM), with low cytotoxicity against mouse peritoneal macrophages (CC(50) 235.80 ± 36.95 μM). Moreover, in silico studies performed to evaluate OA molecular properties and to elucidate the possible mechanism of action over the Leishmania enzyme sterol 14α-demethylase (CYP51) suggested that OA interacts efficiently with CYP51 and could inhibit the ergosterol synthesis pathway. Collectively, these data indicate that OA is a good candidate as leading compound for the development of a new leishmaniasis treatment.

  14. Acid yellow 9 as a dispersing agent for carbon nanotubes: preparation of redox polymer-carbon nanotube composite film and its sensing application towards ascorbic acid and dopamine.

    PubMed

    Kumar, S Ashok; Wang, Sea-Fue; Yang, Thomas C-K; Yeh, Chun-Ting

    2010-08-15

    In this study, we show that acid yellow 9 (4-amino-1-1'-azobenzene-3,4'-disulfonicacid, AY) is a good stabilizing agent for multi-walled carbon nanotubes (MWCNTs). MWCNTs dispersed in AY solution was remained stable about three months and even remained stable after centrifugation at 10,000 rpm for 30 min. Using MWCNTs/AY dispersion, thin-films were prepared on indium tin oxide coated glass electrode and glassy carbon electrodes. Further, dried films of MWCNTs/AY were subjected to electropolymerization in 0.1M H(2)SO(4) solution. Adsorbed AY molecules on MWCNTs get polymerized and they yield a polymer-MWCNTs nanocomposite film on electrode surface which is found to be electrochemically active in wide pH range (1-11). Characterization studies were performed using cyclic voltammetry and SEM. These studies are supported that hybrid material PAY/MWCNTs was obtained. Moreover, newly synthesized PAY-MWCNTs composite film showed excellent electrocatalytic activity towards oxidation of dopamine (DA) and ascorbic acid (AA) with high sensitivity in physiological pH. Linear sweep voltammetry was employed to the determination of DA in the presence of AA in the range of 2x10(-7) to 1.4x10(-6) M. Amperometry was employed to determination of AA at 0.0 V in the range from 1x10(-6) to 5.6x10(-5) M, and DA, uric acid are not interfered on the steady-state current of AA. In addition, real samples such as dopamine injection and AA spiked into human urine were analyzed using PAY/MWCNTs composite modified electrode and satisfactory results were obtained.

  15. Comparison of nucleic acid extraction platforms for detection of select biothreat agents for use in clinical resource limited settings.

    PubMed

    Shipley, Michelle A; Koehler, Jeffrey W; Kulesh, David A; Minogue, Timothy D

    2012-10-01

    High-quality nucleic acids are critical for optimal PCR-based diagnostics and pathogen detection. Rapid sample processing time is important for the earliest administration of therapeutic and containment measures, especially in the case of biothreat agents. In this context, we compared the Fujifilm QuickGene-Mini80 to Qiagen's QIAamp Mini Purification kits for extraction of DNA and RNA for potential use in austere settings. Qiagen (QIAamp) column-based extraction is the currently recommended purification platform by United States Army Medical Research Institute for Infectious Diseases for both DNA and RNA extraction. However, this sample processing system requires dedicated laboratory equipment including a centrifuge. In this study, we investigated the QuickGene-Mini80, which does not require centrifugation, as a suitable platform for nucleic acid extraction for use in resource-limited locations. Quality of the sample extraction was evaluated using pathogen-specific, real-time PCR assays for nucleic acids extracted from viable and γ-irradiated Bacillus anthracis, Yersinia pestis, vaccinia virus, Venezuelan equine encephalitis virus, or B. anthracis spores in buffer or human whole blood. QuickGene-Mini80 and QIAamp performed similarly for DNA extraction regardless of organism viability. It was noteworthy that γ-irradiation did not have a significant impact on real-time PCR for organism detection. Comparison with QIAamp showed a less than adequate performance of the Fujifilm instrument for RNA extraction. However, QuickGene-Mini80 remains a viable alternative to QIAamp for DNA extraction for use in remote settings due to extraction quality, time efficiency, reduced instrument requirements, and ease of use.

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

    PubMed

    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: CH3CO3H + Et(C5H4)C(═S)NH2 → CH3CO2H + Et(C5H4)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, H3S2O2. 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. Mitochondrial dysfunction and death in motor neurons exposed to the glutathione-depleting agent ethacrynic acid.

    PubMed

    Rizzardini, M; Lupi, M; Bernasconi, S; Mangolini, A; Cantoni, L

    2003-03-15

    This study investigated the mechanisms of toxicity of glutathione (GSH) depletion in one cell type, the motor neuron. Ethacrynic acid (EA) (100 microM) was added to immortalized mouse motor neurons (NSC-34) to deplete both cytosolic and mitochondrial glutathione rapidly. This caused a drop in GSH to 25% of the initial level in 1 h and complete loss in 4 h. This effect was accompanied by enhanced generation of reactive oxygen species (ROS) with a peak after 2 h of exposure, and by signs of mitochondrial dysfunction such as a decrease in 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyltetrazolium bromide (MTT) (30% less after 4 h). The increase in ROS and the MTT reduction were both EA concentration-dependent. Expression of heme oxygenase-1 (HO-1), a marker of oxidative stress, also increased. The mitochondrial damage was monitored by measuring the mitochondrial membrane potential (MMP) from the uptake of rhodamine 123 into mitochondria. MMP dropped (20%) after only 1 h exposure to EA, and slowly continued to decline until 3 h, with a steep drop at 5 h (50% decrease), i.e. after the complete GSH loss. Quantification of DNA fragmentation by the TUNEL technique showed that the proportion of cells with fragmented nuclei rose from 10% after 5 h EA exposure to about 65% at 18 h. These results indicate that EA-induced GSH depletion rapidly impairs the mitochondrial function of motor neurons, and this precedes cell death. This experimental model of oxidative toxicity could be useful to study mechanisms of diseases like spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS), where motor neurons are the vulnerable population and oxidative stress has a pathogenic role.

  18. Managing potential drug-drug interactions between gastric acid-reducing agents and antiretroviral therapy: experience from a large HIV-positive cohort.

    PubMed

    Lewis, J M; Stott, K E; Monnery, D; Seden, K; Beeching, N J; Chaponda, M; Khoo, S; Beadsworth, M B J

    2016-02-01

    Drug-drug interactions between antiretroviral therapy and other drugs are well described. Gastric acid-reducing agents are one such class. However, few data exist regarding the frequency of and indications for prescription, nor risk assessment in the setting of an HIV cohort receiving antiretroviral therapy. To assess prevalence of prescription of gastric acid-reducing agents and drug-drug interaction within a UK HIV cohort, we reviewed patient records for the whole cohort, assessing demographic data, frequency and reason for prescription of gastric acid-reducing therapy. Furthermore, we noted potential drug-drug interaction and whether risk had been documented and mitigated. Of 701 patients on antiretroviral therapy, 67 (9.6%) were prescribed gastric acid-reducing therapy. Of these, the majority (59/67 [88.1%]) were prescribed proton pump inhibitors. We identified four potential drug-drug interactions, which were appropriately managed by temporally separating the administration of gastric acid-reducing agent and antiretroviral therapy, and all four of these patients remained virally suppressed. Gastric acid-reducing therapy, in particular proton pump inhibitor therapy, appears common in patients prescribed antiretroviral therapy. Whilst there remains a paucity of published data, our findings are comparable to those in other European cohorts. Pharmacovigilance of drug-drug interactions in HIV-positive patients is vital. Education of patients and staff, and accurate data-gathering tools, will enhance patient safety.

  19. In Vitro, In Silico and In Vivo Studies of Ursolic Acid as an Anti-Filarial Agent

    PubMed Central

    Kalani, Komal; Kushwaha, Vikas; Sharma, Pooja; Verma, Richa; Srivastava, Mukesh; Khan, Feroz; Murthy, P. K.; Srivastava, Santosh Kumar

    2014-01-01

    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. PMID:25375886

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

    EPA Science Inventory

    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...

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

    PubMed

    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.

  2. Effect of salicylic acid on Fusarium graminearum, the major causal agent of fusarium head blight in wheat.

    PubMed

    Qi, Peng-Fei; Johnston, Anne; Balcerzak, Margaret; Rocheleau, Hélène; Harris, Linda J; Long, Xiang-Yu; Wei, Yu-Ming; Zheng, You-Liang; Ouellet, Thérèse

    2012-03-01

    Salicylic acid (SA) is one of the key signal molecules in regulating plant resistance to diverse pathogens. In Arabidopsis thaliana, it is predominantly associated with resistance against biotrophic and hemibiotrophic pathogens, and triggering systemic acquired resistance. In contrast, the effect of SA on the defence efficiency of wheat against fusarium head blight (FHB) and its causal agent, Fusarium graminearum, is still poorly understood. Here we show that the F. graminearum mycelial growth and conidia germination were significantly inhibited, and eventually halted in the presence of increasing concentration of SA in both liquid and solid media. Addition of SA also significantly reduced the production of the mycotoxin deoxynivalenol (DON). However the inhibitory effect of SA required acidic growth conditions to be observed while basic conditions allowed F. graminearum to use SA as a carbon source. High performance liquid chromatography (HPLC) analysis confirmed the capacity of F. graminearum to metabolize SA. To better understand the effect of SA on F. graminearum mycelial growth, we have compared the expression profiles of SA-treated and untreated F. graminearum liquid cultures after 8 and 24 h of treatment, using an F. graminearum custom-commercial microarray. The microarray analysis suggested that F. graminearum can metabolize SA through either the catechol or gentisate pathways that are present in some fungal species. Inoculation of F. graminearum conidia in a SA-containing solution has led to reduced FHB symptoms in the very susceptible Triticum aestivum cv. Roblin. In contrast, no inhibition was observed when SA and conidia were inoculated sequentially. The expression patterns for the wheat PR1, NPR1, Pdf1.2, and PR4 genes, a group of indicator genes for the defence response, suggested that SA-induced resistance contributed little to the reduction of symptoms in our assay conditions. Our results demonstrate that, although F. graminearum has the capacity to

  3. Design, synthesis and evaluation of a new Mn - Contrast agent for MR imaging of myocardium based on the DTPA-phenylpentadecanoic acid complex

    NASA Astrophysics Data System (ADS)

    Belyanin, Maxim L.; Stepanova, Elena V.; Valiev, Rashid R.; Filimonov, Victor D.; Usov, Vladimir Y.; Borodin, Oleg Y.; Ågren, Hans

    2016-11-01

    In the present paper we describe the first synthesis and evaluation of a novel Mn (II) complex (DTPA-PPDA Mn (II)) which contains a C-15 fatty acid moiety that has high affinity to the heart muscle. The complexation energy of DTPA-PPDA Mn (II) evaluated by quantum chemistry methodology indicates that it essentially exceeds the corresponding value for the known DTPA Mn (II) complex. Molecular docking revealed that the affinity of the designed complex to the heart-type transport protein H-FABP well exceeds that of lauric acid. Phantom experiments in low-field MRI the designed contrast agent provides MR imaging comparable to gadopentetic acid.

  4. The behavior and importance of lactic acid complexation in Talspeak extraction systems

    SciTech Connect

    Grimes, Travis S.; Nilsson, Mikael; Nash, Kenneth L.

    2008-07-01

    Advanced partitioning of spent nuclear fuel in the UREX +la process relies on the TALSPEAK process for separation of fission-product lanthanides from trivalent actinides. The classic TALSPEAK utilizes an aqueous medium of both lactic acid and diethylenetriaminepentaacetic acid and the extraction reagent di(2-ethylhexyl)phosphoric acid in an aromatic diluent. In this study, the specific role of lactic acid and the complexes involved in the extraction of the trivalent actinides and lanthanides have been investigated using {sup 14}C-labeled lactic acid. Our results show that lactic acid partitions between the phases in a complex fashion. (authors)

  5. Ecofriendly control of potato late blight causative agent and the potential role of lactic acid bacteria: a review.

    PubMed

    Axel, Claudia; Zannini, Emanuele; Coffey, Aidan; Guo, Jiahui; Waters, Deborah M; Arendt, Elke K

    2012-10-01

    In times of increasing societal pressure to reduce the application of pesticides on crops, demands for environmentally friendly replacements have intensified. In the case of late blight, a devastating potato plant disease, the historically most widely known plant destroyer has been the oomycete Phytophthora infestans. To date, the most important strategy for control of this pathogen has been the frequent application of fungicides. Due to the aforementioned necessity to move away from traditional chemical treatments, many studies have focused on finding alternative ecofriendly biocontrol systems. In general, due to the different modes of actions (i.e. antagonistic effects or induction of plant defence mechanisms), the use of microorganisms as biological control agents has a definite potential. Amongst them, several species of lactic acid bacteria have been recognised as producers of bioactive metabolites which are functional against a broad spectrum of undesirable microorganisms, such as fungi, oomycetes and other bacteria. Thus, they may represent an interesting tool for the development of novel concepts in pest management. This review describes the present situation of late blight disease and summarises current literature regarding the biocontrol of the phytopathogen P. infestans using antagonistic microorganisms.

  6. Design, synthesis and in vitro evaluation of novel dehydroabietic acid derivatives containing a dipeptide moiety as potential anticancer agents.

    PubMed

    Huang, Xiao-Chao; Jin, Le; Wang, Meng; Liang, Dong; Chen, Zhen-Feng; Zhang, Ye; Pan, Ying-Ming; Wang, Heng-Shan

    2015-01-07

    A series of novel dehydroabietic acid (DHA) chiral dipeptide derivatives were designed and synthesized as potent antitumor agents. The inhibitory activities of these compounds against NCI-H460 (lung), HeLa (epithelial cervical) and MGC-803 (gastric) human cancer cell lines were estimated by MTT assay in vitro. The antitumor activities screening indicated that many compounds showed moderate to high levels of antitumor activities against these three cancer cell lines and most of these compounds displayed more potent inhibitory activities compared with commercial anticancer drug 5-fluorouracil (5-FU). The induction of apoptosis and affects on the cell cycle distribution with compound 8k were investigated by acridine orange/ethidium bromide staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, flow cytometry and the activities of caspase-3 and -9 assay in Hela cells, which exhibited that the compound could induce cell apoptosis in Hela cells. In addition, further investigation showed that apoptosis were associated with loss of mitochondrial membrane potential, enhancement of mitochondrial cytochrome c release and intracellular ROS production, elevation of Bax expression, down-regulation of Bcl-2, and the activation of caspase-9 and -3.

  7. First Chemical Feature Based Pharmacophore Modeling of Potent Retinoidal Retinoic Acid Metabolism Blocking Agents (RAMBAs): Identification of Novel RAMBA Scaffolds

    PubMed Central

    Purushottamachar, Puranik; Patel, Jyoti B.; Gediya, Lalji K; Clement, Omoshile O.; Njar, Vincent C. O.

    2011-01-01

    The first three-dimensional (3D) pharmacophore model was developed for potent retinoidal retinoic acid metabolism blocking agents (RAMBAs) with IC50 values ranging from 0.0009 to 5.84 nM. The seven common chemical features in these RAMBAs as deduced by the Catalyst/HipHop program include five hydrophobic groups (hydrophobes), one hydrogen bond acceptor (HBA) and one ring aromatic group. Using the pharmacophore model as a 3D search query against NCI and Maybridge conformational Catalyst formatted databases; we retrieved several compounds with different structures (scaffolds) as hits. Twenty one retrieved hits were tested for RAMBA activity at 100 nM concentration. The most potent of these compounds, NCI10308597 and HTS01914 showed inhibitory potencies less (54.7% and 53.2%, respectively, at 100 nM) than those of our best previously reported RAMBAs VN/12-1 and VN/14-1 (90% and 86%, respectively, at 100 nM). Docking studies using a CYP26A1 homology model revealed that our most potent RAMBAs showed similar binding to the one observed for a series of RAMBAs reported previously by others. Our data shows the potential of our pharmacophore model in identifying structurally diverse and potent RAMBAs. Further refinement of the model and searches of other robust databases is currently in progress with a view to identifying and optimizing new leads. PMID:22130607

  8. Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells

    PubMed Central

    Zhang, Lumin; Chen, Liuxi; Zhang, Xiaomin; Liang, Xiao; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming

    2016-01-01

    Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway. PMID:27557491

  9. Salvianolic acid B, a novel autophagy inducer, exerts antitumor activity as a single agent in colorectal cancer cells.

    PubMed

    Jing, Zhao; Fei, Weiqiang; Zhou, Jichun; Zhang, Lumin; Chen, Liuxi; Zhang, Xiaomin; Liang, Xiao; Xie, Jiansheng; Fang, Yong; Sui, Xinbing; Han, Weidong; Pan, Hongming

    2016-09-20

    Salvianolic Acid B (Sal B), an active compound extracted from the Chinese herb Salvia miltiorrhiza, is attracting more and more attention due to its biological activities, including antioxidant, anticoagulant and antitumor effects. However, autophagy induction in cancer cells by Sal B has never been recognized. In this study, we demonstrated that Sal B induced cell death and triggered autophagy in HCT116 and HT29 cells in a dose-dependent manner. Specific inhibition of autophagy by 3-MA or shRNA targeting Atg5 rescued Sal B-induced cell death in vitro and in vivo, suggesting that Sal B-induced autophagy may play a pro-death role and contribute to the cell death of colorectal cancer cell lines. Furthermore, AKT/mTOR signaling pathway was demonstrated to be a critical mediator in regulating Sal B-induced cell death. Overexpression of AKT by the transfection with AKT plasmid or pretreatment with insulin decreased Sal B-induced autophagy and cell death. Inversely, inhibition of AKT by LY294002 treatment markedly enhanced Sal B-induced autophagy and cell death. Taken together, our results demonstrate, for the first time, that Sal B is a novel autophagy inducer and exerts its antitumor activity as a single agent in colorectal cancer cells through the suppression of AKT/mTOR pathway.

  10. Synthesis and Biological Evaluation of Novel Dehydroabietic Acid Derivatives Conjugated with Acyl-Thiourea Peptide Moiety as Antitumor Agents

    PubMed Central

    Jin, Le; Qu, Hong-En; Huang, Xiao-Chao; Pan, Ying-Ming; Liang, Dong; Chen, Zhen-Feng; Wang, Heng-Shan; Zhang, Ye

    2015-01-01

    A series of dehydroabietic acid (DHAA) acyl-thiourea derivatives were designed and synthesized as potent antitumor agents. The in vitro pharmacological screening results revealed that the target compounds exhibited potent cytotoxicity against HeLa, SK-OV-3 and MGC-803 tumor cell lines, while they showed lower cytotoxicity against HL-7702 normal human river cells. Compound 9n (IC50 = 6.58 ± 1.11 μM) exhibited the best antitumor activity against the HeLa cell line and even displayed more potent inhibitory activity than commercial antitumor drug 5-FU (IC50 = 36.58 ± 1.55 μM). The mechanism of representative compound 9n was then studied by acridine orange/ethidium bromide staining, Hoechst 33,258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay and flow cytometry, which illustrated that this compound could induce apoptosis in HeLa cells. Cell cycle analysis indicated that compound 9n mainly arrested HeLa cells in the S phase stage. Further investigation demonstrated that compound 9n induced apoptosis of HeLa cells through a mitochondrial pathway. PMID:26132564

  11. Degradation of sunscreen agent p-aminobenzoic acid using a combination system of UV irradiation, persulphate and iron(II).

    PubMed

    Xue, Yicen; Dong, Wenbo; Wang, Xiaoning; Bi, Wenlong; Zhai, Pingping; Li, Hongjing; Nie, Minghua

    2016-03-01

    Increased usage and discharge of sunscreens have led to ecological safety crisis, and people are developing the advanced oxidation processes (AOPs) to treat them. The present study aimed to determine the degradation efficiency and mechanism of the sunscreen agent p-aminobenzoic acid (PABA) using the UV/Fe(2+)/persulphate (PS) method. A series of irradiation experiments were conducted to optimise the system conditions and to study the impacts of the natural anion. Free radicals and degradation products were identified in order to clarify the degradation mechanism. Initial PS and Fe(2+) concentrations showed significant impacts on PABA degradation. Natural anions, such as Cl(-), NO3 (-), H2PO4 (-) and HCO3 (-), impeded PABA degradation because of ion (Fe(2+)) capture, radical scavenging or pH effects. Hydroxyl (HO·) and sulphate (SO4 (·-)) radicals were two main radicals observed in the UV/Fe(2+)/PS system; of these, SO4 (·-) showed greater effects on PABA degradation. Over 99 % of the available PABA was completely degraded into carbon dioxide (CO2) and water (H2O) by the UV/Fe(2+)/PS system, and the remaining PABA participated in complex radical reactions. By-products were identified by total ion chromatography and mass spectrometry. Our research provides a treatment process for PABA with high degradation efficiency and environmental safety and introduces a new strategy for sunscreen degradation.

  12. Salvianolic acid A, a polyphenolic derivative from Salvia miltiorrhiza bunge, as a multifunctional agent for the treatment of Alzheimer's disease.

    PubMed

    Cao, Ying Ying; Wang, Ling; Ge, Hu; Lu, Xi Lin; Pei, Zhong; Gu, Qiong; Xu, Jun

    2013-08-01

    The effects of Salvianolic acid A (Sal A) on the treatment of Alzheimer's disease (AD) were investigated. Sal A significantly inhibits amyloid beta [Formula: see text] self-aggregation and disaggregates pre-formed [Formula: see text] fibrils, reduces metal-induced [Formula: see text] aggregation through chelating metal ions, and blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells. Sal A protects cells against [Formula: see text]-induced toxicity. Furthermore, Sal A, possibly because of the effects of decreasing toxicity effects of [Formula: see text] species, alleviates [Formula: see text]-induced paralysis in transgenic Caenorhabditis elegans. Circular dichroism (CD) experiments and Molecular dynamic (MD) simulations demonstrate that Sal A inhibits [Formula: see text] self-aggregation through binding to the C-terminus of [Formula: see text], and therefore stabilizing the [Formula: see text]-helical conformations. Altogether, our data show that Sal A, as the multifunctional agent, is likely to be promising therapeutics for AD.

  13. Synthesis, Aqueous Reactivity, and Biological Evaluation of Carboxylic Acid Ester-Functionalized Platinum–Acridine Hybrid Anticancer Agents

    PubMed Central

    Graham, Leigh A.; Suryadi, Jimmy; West, Tiffany K.; Kucera, Gregory L.; Bierbach, Ulrich

    2012-01-01

    The synthesis of platinum–acridine hybrid agents containing carboxylic acid ester groups is described. The most active derivatives and the unmodified parent compounds showed up to 6-fold higher activity in ovarian cancer (OVCAR-3) and breast cancer (MCF-7, MDA-MB-23) cell lines than cisplatin. Inhibition of cell proliferation at nanomolar concentrations was observed in pancreatic (PANC-1) and non-small cell lung cancer cells (NSCLC, NCI-H460) of 80- and 150-fold, respectively. Introduction of the ester groups did not affect the cytotoxic properties of the hybrids, which form the same monofunctional–intercalative DNA adducts as the parent compounds, as demonstrated in a plasmid unwinding assay. In-line high-performance liquid chromatography and electrospray mass spectrometry (LC-ESMS) shows that the ester moieties undergo platinum-mediated hydrolysis in a chloride concentration-dependent manner to form carboxylate chelates. Potential applications of the chloride-sensitive ester hydrolysis as a self-immolative release mechanism for tumor-selective delivery of platinum–acridines are discussed. PMID:22871158

  14. Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant.

    PubMed

    Prior, A; Moldovan, R C; Crommen, J; Servais, A C; Fillet, M; de Jong, G J; Somsen, G W

    2016-10-12

    The sensitivity of coupled enantioselective capillary electrophoresis-mass spectrometry (CE-MS) of amino acids (AAs) is often hampered by the chiral selectors in the background electrolyte (BGE). A new method is presented in which the use of a chiral selector is circumvented by employing (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC) as chiral AA derivatizing agent and ammonium perfluorooctanoate (APFO) as a volatile pseudostationary phase for separation of the formed diastereomers. Efficient AA derivatization with FLEC was completed within 10 min. Infusion experiments showed that the APFO concentration hardly affects the MS response of FLEC-AAs and presents significantly less ion suppression than equal concentrations of ammonium acetate. The effect of the pH and APFO concentration of the BGE and the capillary temperature were studied in order to achieve optimized enantioseparation. Optimization of CE-MS parameters, such as sheath-liquid composition and flow rate, ESI and MS settings was performed in order to prevent analyte fragmentation and achieve sensitive detection. Selective detection and quantification of 14 chiral proteinogenic AAs was achieved with chiral resolution between 1.2 and 8.6, and limits of detection ranging from 130 to 630 nM injected concentration. Aspartic acid and glutamic acid were detected, but not enantioseparated. The optimized method was applied to the analysis of chiral AAs in cerebrospinal fluid (CSF). Good linearity (R(2) > 0.99) and acceptable peak area and electrophoretic mobility repeatability (RSDs below 21% and 2.4%, respectively) were achieved for the chiral proteinogenic AAs, with sensitivity and chiral resolution mostly similar to obtained for standard solutions. Next to l-AAs, endogenous levels of d-serine and d-glutamine could be measured in CSF revealing enantiomeric ratios of 4.8%-8.0% and 0.34%-0.74%, respectively, and indicating the method's potential for the analysis of low concentrations of d-AAs in presence of

  15. Gas chromatography-mass spectrometry of hexafluoroacetone derivatives: First time utilization of a gaseous phase derivatizing agent for analysis of extraterrestrial amino acids.

    PubMed

    Geffroy-Rodier, C; Buch, A; Sternberg, R; Papot, S

    2012-07-06

    Within the perspective of the current and next space missions to Mars (MSL 2011 and Exomars 2016-2018), the detection and enantioselective separation of building blocks such as the amino acids are important subjects which are becoming fundamental for the search for traces of life on the surface and subsurface of Mars. In this work, we have developed and optimized a method adapted to space experimentation to derivatize and analyze amino acids, using hexafluoroacetone as the derivatizing agent. The temperature, duration of the derivative transfer to the analyser, and chromatographic separation parameters have been optimized to meet the instrument design constraints imposed on devices for extraterrestrial experiments. The work presented in this rationale has established that hexafluoroacetone, in addition to its intrinsic qualities, such as the production of light-weight derivatives (no racemization) and great resistance to the drastic operating conditions, has indeed facilitated simple and fast derivatization that appears to be suitable for in situ analysis in space. By using hexafluoroacetone as the derivatizing agent, we successfully identified, 21 amino acids including 12 of the 20 proteinic amino acids without stirring or extraction steps. Ten of these derivatized amino acids were enantioselectively separated. The precision and accuracy measurements for the D/L ratio showed that the proposed method was also suitable for the determination of both enantioselective forms of most of the tested amino acids. The limits of detection obtained were lower than the ppb level of organic molecules detected in Martian meteorites.

  16. Improve the Strength of PLA/HA Composite Through the Use of Surface Initiated Polymerization and Phosphonic Acid Coupling Agent

    PubMed Central

    Wang, Tongxin; Chow, Laurence C.; Frukhtbeyn, Stanislav A.; Ting, Andy Hai; Dong, Quanxiao; Yang, Mingshu; Mitchell, James W.

    2011-01-01

    Bioresorbable composite made from degradable polymers, e.g., polylactide (PLA), and bioactive calcium phosphates, e.g., hydroxyapatite (HA), are clinically desirable for bone fixation, repair and tissue engineering because they do not need to be removed by surgery after the bone heals. However, preparation of PLA/HA composite from non-modified HA usually results in mechanical strength reductions due to a weak interface between PLA and HA. In this study, a calcium-phosphate/phosphonate hybrid shell was developed to introduce a greater amount of reactive hydroxyl groups onto the HA particles. Then, PLA was successfully grafted on HA by surface-initiated polymerization through the non-ionic surface hydroxyl groups. Thermogravimetric analysis indiated that the amount of grafted PLA on HA can be up to 7 %, which is about 50 % greater than that from the literature. PLA grafted HA shows significantly different pH dependent ζ-potential and particle size profiles from those of uncoated HA. By combining the phosphonic acid coupling agent and surface initiated polymerization, PLA could directly link to HA through covalent bond so that the interfacial interaction in the PLA/HA composite can be significantly improved. The diametral tensile strength of PLA/HA composite prepared from PLA-grafted HA was found to be over twice that of the composite prepared from the non-modified HA. Moreover, the tensile strength of the improved composite was 23 % higher than that of PLA alone. By varying additional variables, this approach has the potential to produce bioresorbable composites with improved mechanical properties that are in the range of natural bones, and can have wide applications for bone fixation and repair in load-bearing areas. PMID:22399838

  17. Chlorophyll-a analogues conjugated with aminobenzyl-DTPA as potential bifunctional agents for magnetic resonance imaging and photodynamic therapy.

    PubMed

    Li, Guolin; Slansky, Adam; Dobhal, Mahabeer P; Goswami, Lalit N; Graham, Andrew; Chen, Yihui; Kanter, Peter; Alberico, Ronald A; Spernyak, Joseph; Morgan, Janet; Mazurchuk, Richard; Oseroff, Allan; Grossman, Zachary; Pandey, Ravindra K

    2005-01-01

    A clinically relevant photosensitizer, 3-devinyl-3-(1-hexyloxyethyl)pyropheophorbide-a (HPPH, a chlorophyll-a derivative), was conjugated with Gd(III)-aminobenzyl-diethylenetriaminepentaacetic acid (DTPA), an experimental magnetic resonance (MR) imaging agent. In vivo reflectance spectroscopy confirmed tumor uptake of HPPH-aminobenzyl-Gd(III)-DTPA conjugate was higher than free HPPH administered intraveneously (iv) to C3H mice with subcutaneously (sc) implanted radiation-induced fibrosarcoma (RIF) tumor cells. In other experiments, Sprague-Dawley (SD) rats with sc implanted Ward Colon Carcinoma cells yielded markedly increased MR signal intensities from tumor regions-of-interest (ROIs) 24 h post-iv injection of HPPH-aminobenzyl-Gd(III)-DTPA conjugate as compared to unconjugated HPPH. In both in vitro (RIF tumor cells) and in vivo (mice bearing RIF tumors and rats bearing Ward Colon tumors) the conjugate produced significant increases in tumor conspicuity at 1.5 T and retained therapeutic efficacy following PDT. Also synthesized were a series of novel bifunctional agents containing two Gd(III) atoms per HPPH molecule that remained tumor-avid and PDT-active and yielded improved MR tumor conspicuity compared to their corresponding mono-Gd(III) analogues. Administered iv at a MR imaging dose of 10 micromol/kg, these conjugates produced severe skin phototoxicity. However, by replacing the hexyl group of the pyropheophorbide-a with a tri(ethylene glycol) monomethyl ether (PEG-methyl ether), these conjugates produced remarkable MR tumor enhancement at 8 h post-iv injection, significant tumoricidal activity (80% of mice were tumor-free on day 90), and reduced skin phototoxicity compared to their corresponding hexyl ether analogues. The poor water-solubility characteristic of these conjugates was resolved by incorporation into a liposomal formulation. This paper presents the synthesis of tumor-avid contrast enhancing agents for MR imaging and thus represents an important

  18. Comparative in vitro potency of amoxycillin-clavulanic acid and four oral agents against recent North American clinical isolates from a global surveillance study.

    PubMed

    Hoban, D J; Bouchillon, S K; Johnson, J L; Zhanel, G G; Butler, D L; Saunders, K A; Miller, L A; Poupard, J A

    2003-05-01

    The in vitro activity of amoxycillin-clavulanic acid was compared with four comparator oral antimicrobial agents; ampicillin, azithromycin, cefuroxime and trimethoprim-sulphamethoxazole against 4536 recent clinical isolates covering 29 species isolated in the US and Canada between 1997 and 1999. Based upon Minimum inhibitory concentrations (MICs), amoxycillin-clavulanic acid was the most active agent against many Gram-positive species and phenotypes including methicillin susceptible Staphylococcus aureus (MSSA) Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus pneumoniae including penicillin intermediate and macrolide resistant strains and was as active as ampicillin against Streptococcus agalactiae, penicillin resistant S. pneumoniae and viridans streptococci. Against Enterobacteriaceae amoxycillin-clavulanic acid in general, displayed weak activity with only Proteus mirabilis and Proteus vulgaris displaying levels of susceptibility above the 90th percentile. Amoxycillin-clavulanic acid had significant activity against many species of Gram-negative non-Enterobacteriaceae including Haemophilus influenzae, Haemophilus parainfluenzae and Moraxella catarrhalis but negligible activity against Burkholderia cepacia, Pseudomonas aeruginosa and Stenotrophomonas maltophilia. Amoxycillin-clavulanic acid continues to retain excellent activity against the majority of targeted pathogens despite 20 years of clinical use.

  19. Cellular interaction of folic acid conjugated superparamagnetic iron oxide nanoparticles and its use as contrast agent for targeted magnetic imaging of tumor cells

    PubMed Central

    Kumar, Manoj; Singh, Gurpal; Arora, Vikas; Mewar, Sujeet; Sharma, Uma; Jagannathan, NR; Sapra, Sameer; Dinda, Amit K; Kharbanda, Surender; Singh, Harpal

    2012-01-01

    The purpose of the study was to develop tumor specific, water dispersible superparamagnetic iron oxide nanoparticles (SPIONs) and evaluate their efficacy as a contrast agent in magnetic resonance imaging (MRI). We have developed SPIONs capped with citric acid/2-bromo-2-methylpropionic acid which are compact, water dispersible, biocompatible having narrow range of size dispersity (8–10 nm), and relatively high T2 relaxivity (R2 = 222L · mmol−1 · sec−l). The targeting efficacy of unconjugated and folic acid-conjugated SPIONs (FA-SPIONS) was evaluated in a folic acid receptor overexpressing and negative tumor cell lines. Folic acid receptor-positive cells incubated with FA-SPIONs showed much higher intracellular iron content without any cytotoxicity. Ultrastructurally, SPIONs were seen as clustered inside the various stages of endocytic pathways without damaging cellular organelles and possible mechanism for their entry is via receptor mediated endocytosis. In vitro MRI studies on tumor cells showed better T2-weighted images in FA-SPIONs. These findings indicate that FA-SPIONs possess high colloidal stability with excellent sensitivity of imaging and can be a useful MRI contrast agent for the detection of cancer. PMID:22848174

  20. Polyion complex micelle MRI contrast agents from poly(ethylene glycol)-b-poly(l-lysine) block copolymers having Gd-DOTA; preparations and their control of T(1)-relaxivities and blood circulation characteristics.

    PubMed

    Shiraishi, Kouichi; Kawano, Kumi; Maitani, Yoshie; Yokoyama, Masayuki

    2010-12-01

    The current study synthesized macromolecular magnetic resonance imaging (MRI) contrast agents constituted of the poly(ethylene glycol)-b-poly(L-lysine) block copolymer (PEG-P(Lys)). A chelate group, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), was attached to the primary amino group of the block copolymer in desired contents. Gd-DOTA-based macromolecular contrast agents were prepared from PEG-P(Lys) having DOTA (PEG-P(Lys-DOTA) and Gd(III) ions. All of the PEG-P(Lys) block copolymers having gadolinium ions (PEG-P(Lys-DOTA-Gd)) showed higher T(1) relaxivity (per gadolinium), r(1)=5.6-7.3mM(-1)s(-1), than that of a low-molecular-weight gadolinium-chelate, diethylenetriaminepentaacetic acid-gadolinium(III) (Gd-DTPA) at 9.4T. The study prepared the polyion complex (PIC) micelles from the amino groups of the lysine units and an oppositely charged polyanion, poly(methacrylic acid) or dextran sulfate, in an aqueous medium. In contrast, the fully DOTA-attached PEG-P(Lys-DOTA-Gd) formed a PIC with a polycation. Compared with partially DOTA-attached cationic PEG-P(Lys-DOTA-Gd), this PIC micelle yielded a forty percent decrease of r(1). This r(1) decrease was considered to result from a change in the accessibility of water molecules to gadolinium ions in the micelles' inner core. The r(1) was decreased upon formation of the PIC micelle, and this change proved that our concept worked in vitro. Blood-circulation characteristics of PIC micelles were controlled by means of changing the molecular weight of the counter anion. The PIC micelles accumulated in tumor tissues, and MRI study showed T1W image of axial slice of tumor area was significantly enhanced at 24h after the injection.

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

    PubMed

    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.

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

    PubMed

    Piermartiri, Tetsade; Pan, Hongna; Figueiredo, Taiza H; Marini, Ann M

    2015-11-12

    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.

  3. Effective methylation of phosphonic acids related to chemical warfare agents mediated by trimethyloxonium tetrafluoroborate for their qualitative detection and identification by gas chromatography-mass spectrometry.

    PubMed

    Valdez, Carlos A; Leif, Roald N; Alcaraz, Armando

    2016-08-24

    The effective methylation of phosphonic acids related to chemical warfare agents (CWAs) employing trimethyloxonium tetrafluoroborate (TMO·BF4) for their qualitative detection and identification by gas chromatography-mass spectrometry (GC-MS) is presented. The methylation occurs in rapid fashion (1 h) and can be conveniently carried out at ambient temperature, thus providing a safer alternative to the universally employed diazomethane-based methylation protocols. Optimization of the methylation parameters led us to conclude that methylene chloride was the ideal solvent to carry out the derivatization, and that even though methylated products can be observed surfacing after only 1 h, additional time was not found to be detrimental but beneficial to the process particularly when dealing with analytes at low concentrations (∼10 μg mL(-1)). Due to its insolubility in methylene chloride, TMO·BF4 conveniently settles to the bottom during the reaction and does not produce additional interfering by-products that may further complicate the GC-MS analysis. The method was demonstrated to successfully methylate a variety of Schedule 2 phosphonic acids, including their half esters, resulting in derivatives that were readily detected and identified using the instrument's spectral library. Most importantly, the method was shown to simultaneously methylate a mixture of the organophosphorus-based nerve agent hydrolysis products: pinacolyl methylphosphonate (PMPA), cyclohexyl methylphosphonate (CyMPA) and ethyl methylphosphonate (EMPA) (at a 10 μg mL(-1) concentration each) in a fatty acid ester-rich organic matrix (OPCW-PT-O3) featured in the 38th Organisation for the Prohibition of Chemical Weapons (OPCW) Proficiency Test. In addition, the protocol was found to effectively methylate N,N-diethylamino ethanesulfonic acid and N,N-diisopropylamino ethanesulfonic acid that are products arising from the oxidative degradation of the V-series agents VR and VX respectively. The

  4. 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.

    PubMed

    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

  5. Influence of chelator and near-infrared dye labeling on biocharacteristics of dual-labeled trastuzumab-based imaging agents

    PubMed Central

    Aldrich, Melissa B; Yang, Zhi; Zhou, Nina; Xie, Qing; Liu, Chen; Sevick-Muraca, Eva

    2016-01-01

    Objective To investigate the effect of fluorescent dye labeling on the targeting capabilities of 111In- (DTPA)n-trastuzumab-(IRDye 800)m. Methods Trastuzumab-based conjugates were synthesized and conjugated with diethylenetriaminepentaacetic acid (DTPA) at molar ratios of 1, 2, 3 and 5 and with a fluorescent dye (IRDye 800CW) at molar ratios of 1, 3 and 5. Immunoreactivity and internalization were assessed on SKBR-3 cells, overexpressing human epidermal growth factor receptor 2. The stability in human serum and phosphate-buffered saline (PBS) was evaluated. The biodistribution of dual-labeled conjugates was compared with that of 111In-(DTPA)2-trastuzumab in a SKBR-3 xenograft model to evaluate the effect of dye-to-protein ratio. Results All trastuzumab-based conjugates exhibited a high level of chemical and optical purity. Flow cytometry results showed that increasing dye-to-protein ratios were associated with decreased immunoreactivity. Stability studies revealed that the conjugate was stable in PBS, while in human serum, increased degradation and protein precipitation were observed with increasing dye-to-protein ratios. At 4 h, the percentages of internalization of dual-labeled conjugates normalized by dye-to-protein ratio (m) were 24.88%±2.10%, 19.99%±0.59%, and 17.47%±1.26% for "m" equal to 1, 3, and 5, respectively. A biodistribution study revealed a progressive decrease in tumor uptake with an increase in the dye-to-protein ratios. The liver, spleen and kidney showed a marked uptake with increased dye-to-protein ratios, particularly in the latter. Conclusions With non-specific-site conjugation of the fluorescent dye with a protein based on imaging agent, the increase in dye-to-protein ratios negatively impacted the immunoreactivity and stability, indicating a reduced tumor uptake. PMID:27478322

  6. Development and assessment of an innovative soil-washing process based on the use of cholic acid-derivatives as pollutant-mobilizing agents.

    PubMed

    Berselli, Sara; Benitez, Emilio; Fedi, Stefano; Zannoni, Davide; Medici, Alessandro; Marchetti, Leonardo; Fava, Fabio

    2006-03-05

    Surfactant-aided soil washing is often proposed for the restoration of aged organic pollutant-contaminated soils. As many of commercial surfactants have been found to be toxic and recalcitrant, the opportunity to use in this process cheap, non-toxic, and biodegradable pollutant-mobilizing agents, such as deoxycholic acid (DA), bovine bile (BB), and the residue resulting from DA extraction from BB (BBR), was studied in this work. A soil historically contaminated by chlorinated anilines and benzenes, thiophenes, and several polycyclic aromatic hydrocarbons was suspended at 15% w/v and washed in water or water amended at 1.0% (w/v) with DA, BB, BBR, or Triton X-100 (TX). The resulting effluents were supplemented with nutrients and subjected to aerobic bioremediation. The biogenic agents enhanced the water pollutant elution potential by 230/440%. TX enhanced the same parameter by about 540%; however, it mediated a lower depletion of the initial soil ecotoxicity and a more extensive mobilization of soil constituents with respect to the biogenic agents. Furthermore, TX adversely affected the biotreatability of resulting effluents, by adversely affecting the growth of cultivable bacterial biomass and the structure of eubacterial community of the effluent. On the contrary, the biogenic agents, and in particular DA and BB, enhanced the effluents bioremediation, by sustaining the growth and increasing the complexity of the effluent eubacterial communities. Thus, DA and BB are very promising additives for an effective and environmental friendly soil washing treatment of aged (chloro)organics contaminated soils.

  7. Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging

    PubMed Central

    Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G.

    2015-01-01

    Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early-stage cancer diagnosis. Gadolinium (Gd) (III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high x-ray attenuation coefficient, is an ideal contrast agent candidate for x-ray based CT imaging. Gd metal organic framework (MOF) nanoparticles with tunable size, high Gd (III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multi-modal imaging probes. PMID:26147906

  8. Compatibilization of immiscible poly(lactic acid)/poly(ɛ-caprolactone) blend through electron-beam irradiation with the addition of a compatibilizing agent

    NASA Astrophysics Data System (ADS)

    Shin, Boo Young; Han, Do Hung

    2013-02-01

    The aim of this study was to compatibilize immiscible poly(lactic acid) (PLA)/poly(ɛ-caprolactone) (PCL) blend by using electron-beam radiation method with the addition of a compatibilizing agent. Glycidyl methacrylate (GMA) was chosen as the compatibilizing agent, in the expectation that the GMA plays a role as a monomeric compatibilizer and a reactive agent at the interface between the PLA and the PCL phases. Compatibilization process has been investigated through the melt mixing of the PLA/PCL and the GMA by using a twin-screw extruder and the exposure of the PLA/PCL/GMA mixture to electron-beam radiation at room temperature. The melt mixing process was performed to locate the GMA at the interface, thereby expecting a finer morphology due to the GMA as the monomeric plasticizer. The exposure process was carried out to induce definite interfacial adhesion at the interface through electron-beam initiated cross-copolymerization by the medium of the GMA as the reactive agent. To investigate the results of this compatibilization strategy, the morphological, mechanical, and rheological properties of the blend were analyzed. The morphological study clearly showed the reduced particle size of dispersed PCL domains and significantly improved interfacial adhesion by the electron-beam irradiation with the addition of the GMA. The stress-strain curves of the blends irradiated at less than 20 kGy showed the typical characteristics of ductile materials. The tensile properties of the blend were strongly affected by the dose of irradiation.

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

    PubMed

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

    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 OH and NO2 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.

  10. Benzyl and Methyl Fatty Hydroxamic Acids Based on Palm Kernel Oil as Chelating Agent for Liquid-Liquid Iron(III) Extraction

    PubMed Central

    Haron, Md Jelas; Jahangirian, Hossein; Silong, Sidik; Yusof, Nor Azah; Kassim, Anuar; Rafiee-Moghaddam, Roshanak; Mahdavi, Behnam; Peyda, Mazyar; Abdollahi, Yadollah; Amin, Jamileh

    2012-01-01

    Liquid-liquid iron(III) extraction was investigated using benzyl fatty hydroxamic acids (BFHAs) and methyl fatty hydroxamic acids (MFHAs) as chelating agents through the formation of iron(III) methyl fatty hydroxamate (Fe-MFHs) or iron(III) benzyl fatty hydroxamate (Fe-BFHs) in the organic phase. The results obtained under optimized conditions, showed that the chelating agents in hexane extract iron(III) at pH 1.9 were realized effectively with a high percentage of extraction (97.2% and 98.1% for MFHAs and BFHAs, respectively). The presence of a large amount of Mg(II), Ni(II), Al(III), Mn(II) and Co(II) ions did affect the iron(III) extraction. Finally stripping studies for recovering iron(III) from organic phase (Fe-MFHs or Fe-BFHs dissolved in hexane) were carried out at various concentrations of HCl, HNO3 and H2SO4. The results showed that the desired acid for recovery of iron(III) was 5 M HCl and quantitative recovery of iron(III) was achieved from Fe(III)-MFHs and Fe(III)-BFHs solutions in hexane containing 5 mg/L of Fe(III). PMID:22408444

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

    PubMed

    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

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

    SciTech Connect

    Moore, J.A.

    1995-03-01

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

  13. Identification of Retinoic Acid in a High Content Screen for Agents that Overcome the Anti-Myogenic Effect of TGF-Beta-1

    PubMed Central

    Krueger, Chateen; Hoffmann, F. Michael

    2010-01-01

    Background Transforming growth factor beta 1 (TGF-β1) is an inhibitor of muscle cell differentiation that is associated with fibrosis, poor regeneration and poor function in some diseases of muscle. When neutralizing antibodies to TGF-β1 or the angiotensin II inhibitor losartan were used to reduce TGF-β1 signaling, muscle morphology and function were restored in mouse models of Marfan Syndrome and muscular dystrophy. The goal of our studies was to identify additional agents that overcome the anti-myogenic effect of TGF-β1. Methodology/Principal Findings A high-content cell-based assay was developed in a 96-well plate format that detects the expression of myosin heavy chain (MHC) in C2C12 cells. The assay was used to quantify the dose-dependent responses of C2C12 cell differentiation to TGF-β1 and to the TGF-β1 Type 1 receptor kinase inhibitor, SB431542. Thirteen agents previously described as promoting C2C12 differentiation in the absence of TGF-β1 were screened in the presence of TGF-β1. Only all-trans retinoic acid and 9-cis retinoic acid allowed a maximal level of C2C12 cell differentiation in the presence of TGF-β1; the angiotensin-converting enzyme inhibitor captopril and 10 nM estrogen provided partial rescue. Vitamin D was a potent inhibitor of retinoic acid-induced myogenesis in the presence of TGF-β1. TGF-β1 inhibits myoblast differentiation through activation of Smad3; however, retinoic acid did not inhibit TGF-β1-induced activation of a Smad3-dependent reporter gene in C2C12 cells. Conclusions/Significance Retinoic acid alleviated the anti-myogenic effect of TGF-β1 by a Smad3-independent mechanism. With regard to the goal of improving muscle regeneration and function in individuals with muscle disease, the identification of retinoic acid is intriguing in that some retinoids are already approved for human therapy. However, retinoids also have well-described adverse effects. The quantitative, high-content assay will be useful to screen for

  14. Identification of linoleic acid, a main component of the n-hexane fraction from Dryopteris crassirhizoma, as an anti-Streptococcus mutans biofilm agent.

    PubMed

    Jung, Ji-Eun; Pandit, Santosh; Jeon, Jae-Gyu

    2014-01-01

    Dryopteris crassirhizoma is a semi-evergreen plant. Previous studies have shown the potential of this plant as an agent for the control of cariogenic biofilms. In this study, the main antibacterial components of the plant were identified by correlating gas chromatography-mass spectrometry data with the antibacterial activity of chloroform and n-hexane fractions and then evaluating the activity of the most potent antibacterial component against Streptococcus mutans UA159 biofilms. The most potent antibacterial component was linoleic acid, a main component of the n-hexane fraction. Linoleic acid reduced viability in a dose dependent manner and reduced biofilm accumulation during initial and mature biofilm formation. Furthermore, when the biofilms were briefly treated with linoleic acid (10 min/treatment, a total of six times), the dry weight of the biofilms was significantly diminished. In addition, the anti-biofilm activity of the n-hexane fraction was similar to that of linoleic acid. These results suggest that the n-hexane fraction of D. crassirhizoma and linoleic acid may be useful for controlling cariogenic biofilms.

  15. Investigation of the Prebiotic Synthesis of Amino Acids and RNA Bases from CO2 using FeS/H2S as a Reducing Agent

    NASA Technical Reports Server (NTRS)

    Keefe, Anthony D.; Miller, Stanley L.; McDonald, Gene; Bada, Jeffrey

    1995-01-01

    An autotrophic theory of the origin of metabolism and life has been proposed in which carbon dioxide is reduced by ferrous sulfide and hydrogen sulfide by means of a reversed citric acid cycle, leading to the production of amino acids. Similar processes have been proposed for purine synthesis. Ferrous sulfide is a strong reducing agent in the presence of hydrogen sulfide and can produce hydrogen as well as reduce alkenes, alkynes, and thiols to saturated hydrocarbons and reduce ketones to thiols. However, the reduction of carbon dioxide has not been demonstrated. We show here that no amino acids, purines, or pyrimidines are produced from carbon dioxide with the ferrous sulfide and hydrogen sulfide system. Furthermore, this system does not produce amino acids from carboxylic acids by reductive amination and carboxylation. Thus, the proposed autotrophic theory, using carbon dioxide, ferrous sulfide, and hydrogen sulfide, lacks the robustness needed to be a geological process and is, therefore, unlikely to have played a role in the origin of metabolism or the origin of life.

  16. Investigation of the Prebiotic Synthesis of Amino Acids and RNA Bases from CO2 Using FeS/H2S As a Reducing Agent

    NASA Technical Reports Server (NTRS)

    Keefe, Anthony D.; Miller, Stanley L.; McDonald, Gene; Bada, Jeffrey

    1995-01-01

    An autotrophic theory of the origin of metabolism and life has been proposed in which carbon dioxide is reduced by ferrous sulfide and hydrogen sulfide by means of a reversed citric acid cycle, leading to the production of amino acids. Similar processes have been proposed for purine synthesis. Ferrous sulfide is a strong reducing agent in the presence of hydrogen sulfide and can produce hydrogen as well as reduce alkenes, alkynes, and thiols to saturated hydrocarbons and reduce ketones to thiols. However, the reduction of carbon dioxide has not been demonstrated. We show here that no amino acids, purities, or pyrimidines are produced from carbon dioxide with the ferrous sulfide and hydrogen sulfide system. Furthermore, this system does not produce amino acids from carboxylic acids by reductive amination and carboxylation. Thus, the proposed autotrophic theory, using carbon dioxide, ferrous sulfide, and hydrogen sulfide, lacks the robustness needed to be a geological process and is, therefore, unlikely to have played a role In the origin of metabolism or the origin of life.

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

    PubMed

    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.

  18. Design and Evaluation of a Novel Trifluorinated Imaging Agent for Assessment of Bile Acid Transport Using Fluorine Magnetic Resonance Imaging

    PubMed Central

    Vivian, Diana; Cheng, Kunrong; Khurana, Sandeep; Xu, Su; Dawson, Paul A.; Raufman, Jean-Pierre; Polli, James E.

    2014-01-01

    Previously, we developed a trifluorinated bile acid, CA-lys-TFA, with the objective of noninvasively assessing bile acid transport in vivo using 19F magnetic resonance imaging (MRI). CA-lys-TFA was successfully imaged in the mouse gallbladder, but was susceptible to deconjugation in vitro by choloylglycine hydrolase (CGH), a bacterial bile acid deconjugating enzyme found in the terminal ileum and colon. The objective of the present study was to develop a novel trifluorinated bile acid resistant to deconjugation by CGH. CA-sar-TFMA was designed, synthesized, and tested for in vitro transport properties, stability, imaging properties, and its ability to differentially accumulate in the gallbladders of normal mice, compared with mice with known impaired bile acid transport (deficient in the apical sodium-dependent bile acid transporter, ASBT). CA-sar-TFMA was a potent inhibitor and substrate of ASBT and the Na+/taurocholate cotransporting polypeptide. Stability was favorable in all conditions tested, including the presence of CGH. CA-sar-TFMA was successfully imaged and accumulated at 16.1-fold higher concentrations in gallbladders from wild-type mice compared with those from Asbt-deficient mice. Our results support the potential of using MRI with CA-sar-TFMA as a noninvasive method to assess bile acid transport in vivo. PMID:25196788

  19. Newly designed Tc(V)-99m dimercaptosuccinic acid: An agent of high accuracy for the diagnosis of head and neck and soft tissue tumors

    SciTech Connect

    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.

  20. Potential long-acting contraceptive agents: esters of testosterone with alkoxy- and halogeno-substituted carboxylic acids.

    PubMed

    Shafiee, A; Vosooghi, M; Francisco, C G; Freire, R; Hernandez, R; Salazar, J A; Suarez, E; Sotheeswaran, S; Gunatilaka, A A

    1987-01-01

    The chemical synthesis and physical data of several new esters of testosterone (17 beta-hydroxyandrost-4-en-3-one), which contain either a halogeno or an alkoxy substituent in the acid chain, are reported.

  1. Discovery of a potent microtubule-targeting agent: Synthesis and biological evaluation of water-soluble amino acid prodrug of combretastatin A-4 derivatives.

    PubMed

    Yu, Kun; Li, Rong; Yang, Zhuang; Wang, Fang; Wu, Wenshuang; Wang, Xiaoyan; Nie, Chunlai; Chen, Lijuan

    2015-06-01

    Amino acid prodrugs are known to be very useful for improving the aqueous solubility of sparingly water soluble drugs (Drug Discovery Today 2013, 18, 93). Therefore, we synthesized eleven novel combretastatin A-4 amino acid derivatives and evaluated their anti-tumor activities in vitro and in vivo. Among them, compound 15 (valine attached to compound 3, which was shown to be a potent tubulin polymerization inhibitor in our previous study) exhibited high efficacy in tumor-bearing mice, and pharmacokinetic analysis in rats indicated that compound 15 was an effective prodrug as well. Besides, compound 15 significantly inhibited tubulin polymerization in vitro and in vivo by binding to the colchicine binding site. In addition, compound 15 induced cell cycle arrest in the G2/M phase and triggered apoptosis in a caspase-dependent manner. In conclusion, our study showed that compound 15 could have significant anti-tumor activity as a novel microtubule polymerization disrupting agent with improved aqueous solubility.

  2. Evaluation of (1-Sarcosine, 8-Isoleucine) Angiotensin II as a Therapeutic Agent for OLEIC Acid-Induced Pulmonary Edema

    DTIC Science & Technology

    1986-02-01

    experiment. The direct REFERENCES effect of the drug on cardiac function is uncertain. 1. Ogihara T, Yamamoto T, Kumahara Y : Clinical applications These...study we 13. Ogihara T, Hata T, Mikami 1t, Nakamuru M, Maruyama A, Mandai T, Kumahara Y : Sodium depletion and blood pressurefound no depressive...circulation when 1974 2. ()gihara T, Yamamoto T, Kumahara Y : Angiotensin blockade used as a therapeutic agent for ARDS. (letter). Lancet 1:219, 1974

  3. A novel class of lipophilic quinazoline-based folic acid analogues: cytotoxic agents with a folate-independent locus

    PubMed Central

    Skelton, L A; Ormerod, M G; Titley, J; Kimbell, R; Brunton, L A; Jackman, A L

    1999-01-01

    Three lipophilic quinazoline-based aminomethyl pyridine compounds, which differ only in the position of the nitrogen in their pyridine ring, are described. CB300179 (2-pyridine), CB300189 (4-pyridine) and CB30865 (3-pyridine) all inhibited isolated mammalian TS with IC50 values of 508, 250 and 156 nM respectively. CB30865 was the most potent growth inhibitory agent (IC50 values in the range 1– 100 nM for several mouse and human cell types). CB300179 and CB300189 were active in the micromolar range. Against W1L2 cells, CB300179 and CB300189 demonstrated reduced potency in the presence of exogenous thymidine (dThd), and against a W1L2:C1 TS overproducing cell line. In contrast, CB30865 retained activity in these systems. Furthermore, combinations of precursors and end products of folate metabolism, e.g. dThd/hypoxanthine (HX) or leucovorin (LV), did not prevent activity. CB30865 did not interfere with the incorporation of tritiated dThd, uridine or leucine after 4 h. A cell line was raised with acquired resistance to CB30865 (W1L2:R865; > 200-fold), which was not cross-resistant to CB300179 or CB300189. In addition, W1L2:R865 cells were as sensitive as parental cells to agents from all the major chemotherapeutic drug classes. CB300179 and CB300189 induced an S phase accumulation (preventable by co-administration of dThd). No cell cycle redistribution was observed following exposure (4–48 h) to an equitoxic concentration of CB30865. In the NCI anticancer drug-discovery screen, CB30865 displayed a pattern of activity which was not consistent with known anti-tumour agents. These data suggest that CB30865 represents a class of potent potential anti-tumour agents with a novel mechanism of action. © 1999 Cancer Research Campaign PMID:10206279

  4. A novel class of lipophilic quinazoline-based folic acid analogues: cytotoxic agents with a folate-independent locus.

    PubMed

    Skelton, L A; Ormerod, M G; Titley, J; Kimbell, R; Brunton, L A; Jackman, A L

    1999-04-01

    Three lipophilic quinazoline-based aminomethyl pyridine compounds, which differ only in the position of the nitrogen in their pyridine ring, are described. CB300179 (2-pyridine), CB300189 (4-pyridine) and CB30865 (3-pyridine) all inhibited isolated mammalian TS with IC50 values of 508, 250 and 156 nM respectively. CB30865 was the most potent growth inhibitory agent (IC50 values in the range 1-100 nM for several mouse and human cell types). CB300179 and CB300189 were active in the micromolar range. Against W1L2 cells, CB300179 and CB300189 demonstrated reduced potency in the presence of exogenous thymidine (dThd), and against a W1L2:C1 TS overproducing cell line. In contrast, CB30865 retained activity in these systems. Furthermore, combinations of precursors and end products of folate metabolism, e.g. dThd/hypoxanthine (HX) or leucovorin (LV), did not prevent activity. CB30865 did not interfere with the incorporation of tritiated dThd, uridine or leucine after 4 h. A cell line was raised with acquired resistance to CB30865 (W1L2:R865; > 200-fold), which was not cross-resistant to CB300179 or CB300189. In addition, W1L2:R865 cells were as sensitive as parental cells to agents from all the major chemotherapeutic drug classes. CB300179 and CB300189 induced an S phase accumulation (preventable by co-administration of dThd). No cell cycle redistribution was observed following exposure (4-48 h) to an equitoxic concentration of CB30865. In the NCI anticancer drug-discovery screen, CB30865 displayed a pattern of activity which was not consistent with known anti-tumour agents. These data suggest that CB30865 represents a class of potent potential anti-tumour agents with a novel mechanism of action.

  5. Light-controlled cellular internalization and cytotoxicity of nucleic acid-binding agents. Studies in vitro and in zebrafish embryos

    PubMed Central

    Penas, Cristina; Sánchez, Mateo I.; Guerra-Varela, Jorge; Sanchez-Piñón, Laura; Vázquez, M. Eugenio; Mascareñas, José L.

    2016-01-01

    We have synthesized oligoarginine conjugates of selected DNA-binding agents (a bisbenzamidine, acridine and thiazole orange) and demonstrated that the DNA binding and cell internalization properties of such conjugates can be inhibited by appending a negatively charged oligoglutamic tail through a photolabile linker. Irradiation with UV light releases the parent octaarginine conjugates, thus restoring their cell internalization and biological activity. Preliminary assays using zebrafish embryos demonstrates the potential of this prodrug strategy for controlling in vivo cytotoxicity. PMID:26534774

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

    PubMed Central

    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

  7. Petroleum-collecting and dispersing complexes based on oleic acid and nitrogenous compounds as surface-active agents for removing thin petroleum films from water surface.

    PubMed

    Asadov, Ziyafaddin H; Tantawy, Ahmed H; Zarbaliyeva, Ilhama A; Rahimov, Ravan A

    2012-01-01

    Petroleum-collecting and dispersing complexes were synthesized on the basis of oleic acid and nitrogen-containing compounds. Surface-active properties (interfacial tension) of the obtained complexes were investigated by stalagmometric method. Petroleum-collecting and dispersing properties of the oleic acid complexes in diluted (5% wt. water or alcoholic solution) and undiluted form have been studied in waters of varying salinity (distilled, fresh and sea waters). Some of physico-chemical indices of the prepared compounds such as solubility, acid and amine numbers as well as electrical conductivity have been determined. The ability of oleic acid complex with ethylenediamine as petro-collecting and dispersing agent towards different types of petroleum has been studied. The influence of thickness and "age" of the petroleum slick on collecting and dispersing capacity of this complex has been clarified. Surface properties studied included critical micelle concentration (CMC), maximum surface excess (Γ(max)), and minimum surface area (A(min)). Free energies of micellization (ΔG°(mic)) and adsorption (ΔG°(ads)) were calculated.

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

    PubMed

    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.

  9. The use of concentrated monosodium glutamate wastewater as a conditioning agent for adjusting acidity and minimizing ammonia volatilization in livestock manure composting.

    PubMed

    Liu, Li; Kong, Haimin; Lu, Beibei; Wang, Jibing; Xie, Yuan; Fang, Ping

    2015-09-15

    In this study, concentrated monosodium glutamate waste (CMGW) was proposed as a conditioning agent to adjust acidity and decrease ammonia (NH3) volatilization in thermophilic aerobic composting based on two incubation experiments. The results showed that with the addition of CMGW, NH3 volatilization of compost mixture under high temperature phase decreased significantly and pH met the current national standard within 5.5-8.5. When CMGW dosage increased to 2% (v/w), the decrease in NH3 volatilization was as high as 78.9%. This effect was enhanced by repeated application of CMGW. Furthermore, although the electrical conductivity increased with the application of CMGW, both the germination index and the microbial respiration of compost mixture implied that CMGW had no negative effects on the maturity of compost, instead, a comprehensive maturity might be accelerated. It was concluded that CMGW was an optional conditioning agent for thermophilic aerobic composting of livestock manure in regards to adjusting acidity and preventing nitrogen loss from NH3 volatilization.

  10. Impact of biological control agents on fusaric acid secreted from Fusarium oxysporum f. sp. gladioli (Massey) Snyder and Hansen in Gladiolus grandiflorus corms.

    PubMed

    Nosir, Walid; McDonald, Jim; Woodward, Steve

    2011-01-01

    Fusaric acid (FA) (5-n-butylpuridine 2-carboxyl acid), a highly toxic secondary metabolite produced by Fusarium oxysporum strains, plays a significant role in disease development. The abilities of three F. oxysporum f. sp. gladioli (Massey) Snyder and Hansen isolates (G010; 649-91; and 160-57) to produce FA in infected Gladiolus corm tissues was evaluated in vitro in relation to the presence of two biological control agents, Trichoderma harzianum T22, and Aneurinobacillus migulanus. Pathogenicity tests were used to differentiate between the abilities of the F. oxysporum strains to secrete FA. FA was identified using LC/MS and quantified using HPLC. Isolate G010 was significantly more virulent (P < 0.01) on Gladiolus grandiflorus corms; it secretes 1.8 μM FA/g fresh weight corm into inoculated Gladiolus. Moreover, G010 was the only isolate that produced FA among the three examined isolates. There was a correlation between the corm lesion area and the FA secretion ability of F. oxysporum f. sp. gladioli (P < 0.001; r (2) = 0.96). No FA was detected in PDA cultures of F.oxysporum f. sp. gladioli isolates. The presence of T. harzianum T22 appeared to prevent FA secretion into the corms. In the presence of A. migulanus, however, the amount of FA secreted into the corm tissues increased. These results support the use of T. harzianum as an effective biological control agent against F. oxysporum f. sp. gladioli.

  11. Effects of skin preapplication treatments and postapplication cleansing agents on dermal absorption of 2,4-dichlorophenoxyacetic acid dimethylamine by Fischer 344 rats.

    PubMed

    Pelletier, O; Ritter, L; Caron, J

    1990-12-01

    Various methods of preparing dermal application sites in Fischer 344 rats prior to exposure to 2,4-dichlorophenoxyacetic acid dimethylamine salt (2,4-D amine) and the effect of various cleansing agents following exposure were examined by measuring recoveries of 14C-labeled 2,4-D amine in skin, postapplication cleansing solution, blood, and urine. The middorsal area of the rat was the site of application for four treatments tested: (1) hair clipping only, (2) hair clipping followed by an epilatory cream, (3) hair clipping plus shaving with an electrical razor, and (4) as in treatment 3 followed by washing with soap and water. A last preparation was the rat's tail thoroughly brushed with soap and water. The results indicated that the tail retained greater than 75% of the material, thus preventing its absorption into the blood stream and subsequent removal by cleansing. With treatment 1 the dense short hair remaining after clipping impaired the absorption of 2,4-D as evidenced by considerably lower blood and urinary levels than treatments 2-4. With preparations 1-4, 45-61% of the dose was removed with the 7-h postapplication cleansing and a further 5-6% with the subsequent 23-h cleansing. In other studies using preparation 3 above, the following cleansing agents were tested: soap and water, water, isopropanol, acetone, and Rad-Con, a foam-producing cleanser. Rad-Con removed more 2,4-D from the skin than other cleansing agents after 7 h of exposure and more than soap and water after 23 h. The percentages of 2,4-D left on the skin following either 7- or 23-h cleansing with Rad-Con were 8-12%, nearly half those following the other cleansing agents. Cleansing agents other than Rad-Con presented little advantage over soap and water. With all cleansing agents, delaying cleansing from 7 to 23 h after exposure resulted in higher blood and urinary levels of 2,4-D measured 24 h after application.

  12. The impact of extraction with a chelating agent under acidic conditions on the cell wall polymers of mango peel.

    PubMed

    Jamsazzadeh Kermani, Zahra; Shpigelman, Avi; Kyomugasho, Clare; Van Buggenhout, Sandy; Ramezani, Mohsen; Van Loey, Ann M; Hendrickx, Marc E

    2014-10-15

    The objective of this research was to evaluate whether mango peel is a potential source of functional cell wall polymers. To reach this objective, the native pectin polymers (NPP) extracted as alcohol insoluble residue from mango peel, were characterised in terms of uronic acid content, degree of methoxylation, neutral sugar content, and molar mass and compared to citric acid (pH 2.5, 2h at 80°C) extracted polymers, mimicking industrial pectin extraction conditions. Water-solubilised NPP were highly methoxylated having two populations with a Mw of 904 and 83kDa and a degree of methoxylation of 66%. Citric acid extraction with a yield higher than H2SO4 extraction resulted in a very branched pectin with an extremely high DM (83%) and a high molar mass. Comparing the Fourier Transform Infra-Red spectroscopy of extracted and native WSF showed that citric acid remained partially associated to the extracted pectin due to its chelating properties.

  13. Counteracting foaming caused by lipids or proteins in biogas reactors using rapeseed oil or oleic acid as antifoaming agents.

    PubMed

    Kougias, P G; Boe, K; Einarsdottir, E S; Angelidaki, I

    2015-08-01

    Foaming is one of the major operational problems in biogas plants, and dealing with foaming incidents is still based on empirical practices. Various types of antifoams are used arbitrarily to combat foaming in biogas plants, but without any scientific support this action can lead to serious deterioration of the methanogenic process. Many commercial antifoams are derivatives of fatty acids or oils. However, it is well known that lipids can induce foaming in manure based biogas plants. This study aimed to elucidate the effect of rapeseed oil and oleic acid on foam reduction and process performance in biogas reactors fed with protein or lipid rich substrates. The results showed that both antifoams efficiently suppressed foaming. Moreover rapeseed oil resulted in stimulation of the biogas production. Finally, it was reckoned that the chemical structure of lipids, and more specifically their carboxylic ends, is responsible for their foam promoting or foam counteracting behaviour. Thus, it was concluded that the fatty acids and oils could suppress foaming, while salt of fatty acids could generate foam.

  14. Identification of chicoric acid as a hypoglycemic agent from Ocimum gratissimum leaf extract in a biomonitoring in vivo study.

    PubMed

    Casanova, Livia Marques; da Silva, Daniel; Sola-Penna, Mauro; Camargo, Luiza Maria de Magalhães; Celestrini, Deborah de Moura; Tinoco, Luzineide Wanderley; Costa, Sônia Soares

    2014-03-01

    Ocimum gratissimum L. is popularly used to treat diabetes mellitus. The hypoglycemic activity of this medicinal species has been confirmed by in vivo studies. The present study conducted a chemical investigation of a leaf decoction (10% p/v) of O. gratissimum monitored by in vivo hypoglycemic activity assays. Four phenolic substances were identified: L-caftaric acid (1), L-chicoric acid (2), eugenyl-β-D-glucopyranoside (3) and vicenin-2 (4). The acute hypoglycemic activity of the O. gratissimum decoction fractions Og1-S (300 mg/kg), Og1-A (240 mg/kg) and Og1-B (80 mg/kg) was evaluated intraperitoneally in normal and streptozotocin-induced diabetic mice. They reduced glycemia by 63%, 76% and 60% (in 120 min), respectively, in the diabetic mice. Subfractions of Og1-A were also evaluated under the same conditions: Og1-AS (200 mg/kg) and Og1-AP (40 mg/kg) produced a decrease of only 37% and 39%, respectively. Among the major phenolic substances, only chicoric acid (2; 3 mg/kg) reduced significantly the glycemic levels of diabetic mice by 53%, 120 min after treatment. This is the first study describing the hypoglycemic activity of chicoric acid in an animal model of diabetes mellitus. In addition, we suggest that there may be other substances contributing to this activity. Thus, for the first time, a correlation is established between the hypoglycemic activity of O. gratissimum and its chemical composition.

  15. Ent-trachyloban-19-oic acid isolated from Iostephane heterophylla as a promising antibacterial agent against Streptococcus mutans biofilms.

    PubMed

    Hernández, Dulce M; Díaz-Ruiz, Gloria; Rivero-Cruz, Blanca E; Bye, Robert A; Aguilar, María Isabel; Rivero-Cruz, J Fausto

    2012-04-01

    From the roots of Iostephane heterophylla, six known compounds, namely, ent-trachyloban-19-oic acid (1), the mixture of ent-kaur-16-en-19-oic acid (2) and ent-beyer-15-en-19-oic acid (3), xanthorrhizol (4), 16α-hydroxy-ent-kaurane (5) and 16α-hydroxy-ent-kaur-11-en-19-oic acid (6) were isolated using a bioassay-guided fractionation method. The known compounds (1-6) were identified by comparison of their spectroscopic data with reported values in the literature. In an attempt to increase the resultant antimicrobial activity of 1 and 4, a series of reactions was performed on ent-trachyloban-19-oic acid (1) and xanthorrhizol (4), to obtain derivatives 1a, 1b, and 4a-4d. All the isolated compounds (1-6) and the derivatives 1a, 1b, and 4a-4d were evaluated for their antimicrobial activity against two oral pathogens, Streptococcus mutans and Porphyromonas gingivalis associated with caries and periodontal disease, respectively. Compounds 1, 1b, 2+3, 4 and 4d inhibited the growth of S. mutans with concentrations ranging from 4.1 μg/mL to 70.5 μg/mL. No significant activity was found on P. gingivalis except for 4 with an MIC of 6.8 μg/mL. The ability of 1, 1b, 2+3, 4 and 4d to inhibit biofilm formation by S. mutans was evaluated. It was found that 1, 1b, 4 and 4d interfered with the establishment of S. mutans biofilms, inhibiting their development at 32.5, 125.0, 14.1 and 24.4 μg/mL, respectively.

  16. Radioactive diagnostic agent

    SciTech Connect

    Shigematsu, A.; Aihara, M.; Matsuda, M.; Suzuki, A.; Tsuya, A.

    1984-02-07

    A radioactive diagnostic agent for renal cortex, adrenal cortex, myocardium, brain stem, spinal nerve, etc., which comprises as an essential component monoiodoacetic acid wherein the iodine atom is radioactive.

  17. Biomimetic Actinide Chelators: An Update on the Preclinical Development of the Orally Active Hydroxypyridonate Decorporation Agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO)

    PubMed Central

    Abergel, Rebecca J.; Durbin, Patricia W.; Kullgren, Birgitta; Ebbe, Shirley N.; Xu, Jide; Chang, Polly Y.; Bunin, Deborah I.; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Rosen, Chris J.; Shuh, David K.; Raymond, Kenneth N.

    2010-01-01

    The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (> 100 μmol kg−1 day−1) over 28 days under good laboratory practice (GLP) guidelines. Both compounds are on an accelerated development pathway towards clinical use. PMID:20699704

  18. Biomimetic actinide chelators: an update on the preclinical development of the orally active hydroxypyridonate decorporation agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO).

    PubMed

    Abergel, Rebecca J; Durbin, Patricia W; Kullgren, Birgitta; Ebbe, Shirley N; Xu, Jide; Chang, Polly Y; Bunin, Deborah I; Blakely, Eleanor A; Bjornstad, Kathleen A; Rosen, Chris J; Shuh, David K; Raymond, Kenneth N

    2010-09-01

    The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity, and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (>100 micromol kg d) over 28 d under good laboratory practice guidelines. Both compounds are on an accelerated development pathway towards clinical use.

  19. Biomimetic Actinide Chelators: An Update on the Preclinical Development of the Orally Active Hydroxypyridonate Decorporation Agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO)

    SciTech Connect

    Durbin, Patricia W.; Kullgren, Birgitta; Ebbe, Shirley N.; Xu, Jide; Chang, Polly Y.; Bunin, Deborah I.; Blakely, Eleanor A.; Bjornstad, Kathleen A.; Rosen, Chris J.; Shuh, David K.; Raymond, Kenneth N.

    2011-07-13

    The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use. Using a biomimetic approach based on the similar biochemical properties of plutonium(IV) and iron(III), siderophore-inspired multidentate hydroxypyridonate ligands have been designed and are unrivaled in terms of actinide-affinity, selectivity, and efficiency. A perspective on the preclinical development of two hydroxypyridonate actinide decorporation agents, 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO), is presented. The chemical syntheses of both candidate compounds have been optimized for scale-up. Baseline preparation and analytical methods suitable for manufacturing large amounts have been established. Both ligands show much higher actinide-removal efficacy than the currently approved agent, diethylenetriaminepentaacetic acid (DTPA), with different selectivity for the tested isotopes of plutonium, americium, uranium and neptunium. No toxicity is observed in cells derived from three different human tissue sources treated in vitro up to ligand concentrations of 1 mM, and both ligands were well tolerated in rats when orally administered daily at high doses (>100 micromol kg d) over 28 d under good laboratory practice guidelines. Both compounds are on an accelerated development pathway towards clinical use.

  20. Discovery and SARs of Trans-3-Aryl Acrylic Acids and Their Analogs as Novel Anti- Tobacco Mosaic Virus (TMV) Agents

    PubMed Central

    Wu, Meng; Wang, Ziwen; Meng, Chuisong; Wang, Kailiang; Hu, Yanna; Wang, Lizhong; Wang, Qingmin

    2013-01-01

    A series of trans-3-aryl acrylic acids 1–27 and their derivatives 28–34 were prepared and evaluated for their antiviral activity against tobacco mosaic virus (TMV) for the first time. The bioassay results showed that most of these compounds exhibited good antiviral activity against TMV, of which compounds 1, 5, 6, 20, 27 and 34 exhibited significantly higher activity against TMV than commercial Ribavirin both in vitro and in vivo. Furthermore, these compounds have more simple structure than commercial Ribavirin, and can be synthesized more efficiently. These new findings demonstrate that trans-3-aryl acrylic acids and their derivatives represent a new template for antiviral studies and could be considered for novel therapy against plant virus infection. PMID:23418574

  1. A Lanthanum-Tagged Chemotherapeutic Agent HA-Pt to Track the In Vivo Distribution of Hyaluronic Acid Complexes

    PubMed Central

    Forrest, W.C.; Cai, Shuang; Aires, Daniel; Forrest, M. Laird

    2015-01-01

    Hyaluronic acid drug conjugates can target anti-cancer drugs directly to tumor tissue for loco-regional treatment with enhanced bioavailability, local efficacy and reduced toxicity. In this study, the distribution and pharmacokinetics of hyaluronic acid carrier and a conjugated cisplatin anti-cancer drug were tracked by lanthanum (III) [La(III)] affinity tagging of the nanocarrier. The strong binding affinity of La(III) to HA enabled the simple preparation of a physiologically stable complex HA-Pt-La and straightforward simultaneous detection of HA-La and Pt in biological matrices using inductively coupled plasma-mass spectrometry (ICP-MS). Consequently, after subcutaneous injection of HA-Pt-La nanoparticles in human head and neck squamous cell carcinoma (HNSCC) tumor-bearing mice, the HA and Pt content were detected and quantified simultaneously in the plasma, primary tumor, liver and spleen. PMID:26756040

  2. The determination of wear metals in used lubricating oils by flame atomic absorption spectrometry using sulphanilic acid as ashing agent.

    PubMed

    Ekanem, E J; Lori, J A; Thomas, S A

    1997-11-01

    A simple and reliable ashing procedure is proposed for the preparation of used lubricating oil samples for the determination of calcium, magnesium, zinc, iron, chromium and nickel by flame atomic absorption spectrometry. Sulphanilic acid was added to oil samples and the mixture coked and the coke ashed at 550 degrees C. The solutions of the ash were analysed by flame AAS for the metals. The release of calcium, zinc, iron and chromium was improved by the addition of sulphanilic acid to samples. The relative standard deviations of metal concentration results in the initial oil samples were 1.5% for Ca (1500 mg l(-1) level), 0.3% for Mg (100 mg l(-1) level), 3.1% for Zn (1500 mg l(-1) level), 0.7% for Fe (500 mg l(-1) level), 0.02% for Cr (50 mg l(-1) level) and 0.002% for Ni (10 mg l(-1) level). The optimum sample size for efficient metal release was 20 g while the optimum sulphanilic acid to oil ratio was 0.05 g per gram of oil for Zn and Cr and 0.10 g for Ca and Fe. Results obtained by this procedure were highly reproducible and comparable with those obtained for the same samples using standard procedures.

  3. A novel DTPA cross-linking of hyaluronic acid and metal complexation thereof.

    PubMed

    Buffa, Radovan; Běťák, Jiří; Kettou, Sofiane; Hermannová, Martina; Pospíšilová, Lucie; Velebný, Vladimír

    2011-09-27

    Macromolecular conjugates of a natural polysaccharide, hyaluronic acid, with diethylenetriaminepentaacetic acid (DTPA)-metal complexes were synthesized and characterized by FTIR, NMR, SEC-MALLS and ICP analysis. Several parameters of the cross-linking reaction as molecular weight of starting HA, temperature, equivalent of DTPA bis-anhydride, concentration of HA, presence of transacylation catalyst DMAP and reaction time were studied. The mechanism for the reaction was suggested and relationship between the molecular weight assigned by SEC-MALLS, reaction parameters and rheological properties of the final cross-linked products were investigated.

  4. Down-regulation of glutaminase C in human hepatocarcinoma cell by diphenylarsinic acid, a degradation product of chemical warfare agents

    SciTech Connect

    Kita, Kayoko . E-mail: kkayoko@pharm.teikyo-u.ac.jp; Suzuki, Toshihide; Ochi, Takafumi

    2007-05-01

    In a poisonous incident in Kamisu, Japan, it is understood that diphenylarsinic acid (DPAA) was a critical contaminant of ground water. Most patients showed dysfunction of the central nervous system. To understand the overall mechanism of DPAA toxicity and to gain some insight into the application of a remedy specific for intoxication, the molecular target must be clarified. As an approach, a high throughput analysis of cell proteins in cultured human hepatocarcinoma HpG2 exposed to DPAA was performed by two-dimensional electrophoresis (2-DE). Four proteins, which were up- and down-regulated by exposure of cultured HepG2 cells to DPAA, were identified. They were chaperonin containing TCP-1 (CCT) beta subunit, aldehyde dehydrogenase 1 (ALDH1), ribosomal protein P0 and glutaminase C (GAC). Of these, GAC was the only protein that was down-regulated by DPAA exposure, and cellular expression levels were reduced by DPAA in a concentration- and time-dependent manner. Decrease in cellular GAC levels was accompanied by decreased activity of the enzyme, phosphate-activated glutaminase (PAG). Decreased expression of GAC by DPAA was also observed in human cervical carcinoma HeLa and neuroblastoma SH-SY5Y cells. By contrast, no significant changes in GAC protein expression were observed when cells were incubated with arsenite [iAs (III)] and trivalent dimethylarsinous acid [DMA (III)]. In the central nervous system, GAC plays a role in the production of the neurotransmitter glutamic acid. Selective inhibition of GAC expression by DPAA may be a cause of dysfunction of glutamatergic neuronal transmission and the resultant neurological impairments.

  5. Synthesis and biological activity of ester derivatives of mycophenolic acid and acridines/acridones as potential immunosuppressive agents.

    PubMed

    Cholewinski, Grzegorz; Iwaszkiewicz-Grzes, Dorota; Trzonkowski, Piotr; Dzierzbicka, Krystyna

    2016-12-01

    Improved derivatives of mycophenolic acid (MPA) are necessary to reduce the frequency of adverse effects, this drug exerts in treated patients. In this study, MPA was coupled with N-(ω-hydroxyalkyl)-9-acridone-4-carboxamides or N-(ω-hydroxyalkyl)acridine-4-carboxamides to give respective ester conjugates upon Yamaguchi protocol. This esterification required protection of phenol group in MPA. Designed conjugates revealed higher potency in vitro than parent MPA. Acridine derivatives were more active than acridone analogs and length of the alkyl linker between MPA and heterocyclic units influenced the observed cytotoxicity. Derivatives 2b, 2d, 3a, 3b displayed the most promising immunosuppressive activity.

  6. A new boron compound (guanidine biboric acid adduct) as an antitumour agent against Ehrlich ascites carcinoma in mice.

    PubMed

    Ghosh, P; Sur, B; Bag, S P; Sur, P

    1999-01-01

    The inhibitory effects of a new boron compound of guanidine biboric acid adduct (GB) and guanidium chloride (L1) on the growth of ascites tumour in female Swiss mice were studied by monitoring the survival, tumour weight, tumour cell count, transplantability of Ehrlich ascites cells, precursor incorporation and the haematological parameters of the treated mice. 5-Fluorouracil, a known anticancer drug, was used as a positive control. The most important parameter was the survival time, which increased significantly when tumour-bearing mice were treated with the boron compound. Haematological parameters of the treated animals showed minimum toxic effects when boron was coupled with guanidine.

  7. Rapid differentiation of the major causative agents of bacterial meningitis by use of frequency-pulsed electron capture gas-liquid chromatograph: analysis of acids.

    PubMed

    Brooks, J B; Kellogg, D S; Shepherd, M E; Alley, C C

    1980-01-01

    The major causative agents of bacterial meningitis, Haemophilus influenzae serogroup B, Neisseria meningitidis serogroups B and C, Klebsiella pneumoniae, Streptococcus pneumoniae, and two types of Escherichia coli, were cultured in a modified chemically defined Catlin medium and in a commercial version of the unmodified Catlin medium. The spent media were extracted under acidic conditions, and electron-capturing derivatives were prepared by derivatization with trichloroethanol or haptafluorobutyric anhydride. The derivatives were analyzed on a gas chromatograph equipped with a frequency-pulsed electron capture detector and a PEP-2 computer. The data obtained from the study show that these organisms can be easily distinguished from each other on the basis of metabolic products detected in either type of medium. Three different metabolic groups were detected within two serogroups of N. meningitidis. The methods are practical, and the new technique should offer clinical laboratories and hospitals a better method for rapid identification of this important group of pathogens.

  8. Interactions of collagen molecules in the presence of N-hydroxysuccinimide activated adipic acid (NHS-AA) as a crosslinking agent.

    PubMed

    Zhang, Min; Wu, Kun; Li, Guoying

    2011-11-01

    The effect of crosslinking agent on pepsin-soluble bovine collagen solution was examined using N-hydroxysuccinimide activated adipic acid (NHS-AA) as a crosslinker. Electrophoretic patterns indicated that crosslinks formed when NHS-AA was added. A higher polarity level deduced from the changes in the fluorescence emission spectrum of pyrene in the crosslinked collagen solution indicated that the formation of well-ordered aggregates was suppressed. The random aggregation of collagens was also observed by atomic force microscopy (AFM). Furthermore, the association of collagens into fibrils was influenced by crosslinking. Self-assembly was suppressed at 37°C; however, as temperature was increased to 39°C, a small amount of NHS-AA leaded to an improvement in the ability of self-aggregation. Although more random structure was brought about by crosslinking, self-aggregation might still be promoted as temperature was increased, accompanying by the thermal stability improvement of fibrils.

  9. An industry perspective on the use of "atoxigenic" strains of Aspergillus flavus as biological control agents and the significance of cyclopiazonic acid.

    PubMed

    King, Eileen D; Bobby Bassi, Albeit B; Ross, David C; Druebbisch, Bernd

    2011-08-01

    Several nonaflatoxigenic strains of Aspergillus flavus have been registered in the United States to reduce aflatoxin accumulation in maize and other crops, but there may be unintended negative consequences if these strains produce cyclopiazonic acid (CPA). AF36, a nonaflatoxigenic, CPA-producing strain has been shown to produce CPA in treated maize and peanuts. Alternative strains, including Afla-Guard® brand biocontrol agent and K49, do not produce CPA and can reduce both aflatoxin and CPA in treated crops. Chronic toxicity of CPA has not been studied, and recent animal studies show significant harmful effects from short-term exposure to CPA at low doses. Grower and industry confidence in this approach must be preserved through transparency.

  10. Improvement of the CuZn-superoxide dismutase enzyme activity and stability as a therapeutic agent by modification with polysialic acids.

    PubMed

    Wu, Jian Rong; Lin, Yi; Zheng, Zhi Yong; Lin, Chi Chung; Zhan, Xiao Bei; Shen, Ying Qiang

    2010-12-01

    The optimal process for the polysialylation reaction was as follows: polysialicacid (PSA) was activated by periodate oxidation, then coupled to CuZn superoxide dismutase (SOD) with a PSA:SOD molar ratio of 40:1 for 24 h. The resulting polysialylated protein contained 3.9 ± 0.3 mol PSA per mol SOD. SDS-PAGE and atomic force microscopy revealed that the molecular weight of polysialylated SOD was about 90-100 kDa. The average size was 10-15 nm, about four-fold of the native enzyme. Compared to the native enzyme, the activity and stability of the polysialylated SOD, as well as resistance to heat, acid, alkali and proteases present in human digestive system such as pepsin and trypsin, were improved significantly as therapeutic agent.

  11. Near-infrared dye-conjugated amphiphilic hyaluronic acid derivatives as a dual contrast agent for in vivo optical and photoacoustic tumor imaging.

    PubMed

    Miki, Koji; Inoue, Tatsuhiro; Kobayashi, Yasuhito; Nakano, Katsuya; Matsuoka, Hideki; Yamauchi, Fumio; Yano, Tetsuya; Ohe, Kouichi

    2015-01-12

    Amphiphilic hyaluronic acid (HA) derivatives bearing hydrophobic indocyanine green dye derivatives and hydrophilic poly(ethylene glycol) were synthesized through the use of condensation and copper-catalyzed click cyclization reactions. The amphiphilic HA derivatives dissolved in water and formed self-assemblies in which the near-infrared dyes were tightly packed and arranged to form dimers or H-aggregates. By irradiating an aqueous solution of HA derivatives with near-infrared light, photoacoustic signals were detected along with fluorescence emission. Self-assemblies consisting of HA derivatives could smoothly accumulate in tumor tissues by passive tumor targeting. By utilizing HA derivatives as a contrast agent, tumor sites were clearly visualized by optical imaging as well as by photoacoustic tomography.

  12. Synthesis, characterization and in vitro and in vivo investigation of C₃F₈-filled poly(lactic-co-glycolic acid) nanoparticles as an ultrasound contrast agent.

    PubMed

    Wang, Cui-Wei; Yang, Shi-Ping; Hu, He; Du, Jing; Li, Feng-Hua

    2015-03-01

    The present study aimed to prepare perfluoropropane (C3F8)-filled poly(lactic-co-glycolic acid) (PLGA) nanoparticles and investigate the feasibility of using PLGA nanoparticles as an ultrasound contrast agent. The PLGA nanoscale ultrasound contrast agent was prepared using a modified double-emulsion solvent evaporation method. Camphor in the form of a sublimable porogen was added to render the nanoparticles hollow and enable C3F8 gas introduction. Various physicochemical properties of PLGA nanoparticles, including morphology, size and dispersion, were analyzed by electron microscopy and dynamic laser scattering. In vitro ultrasound imaging of C3F8-filled PLGA nanoparticles was also investigated under various imaging conditions. Further in vivo ultrasound imaging was conducted on male rats following intratesticular injection of PLGA nanoparticles. C3F8-filled PLGA nanoparticles with a mean diameter of 152.0±58.08 nm were obtained. Electron microscopy revealed spherical-shaped nanoparticles with smooth surfaces, a capsular morphology and a large hollow within. In vitro ultrasound imaging of hollow PLGA nanoparticles indicated marked signal enhancement. Local intensity of the acoustical signal continued to increase during PLGA-nanoparticle injection into the testicle and the ability of hollow PLGA nanoparticles to enhance ultrasound imaging in vivo was demonstrated. The enhancement image of testicular tissue following injection with C3F8-filled PLGA nanoparticles was sustained for a minimum of five minutes. In conclusion, the hollow C3F8-filled PLGA nanoparticles were demonstrated to have potential for applications as a novel ultrasound contrast agent.

  13. The outcomes of two different bulking agents (dextranomer hyaluronic acid copolymer and polyacrylate-polyalcohol copolymer) in the treatment of primary vesico-ureteral reflux

    PubMed Central

    Taşkinlar, Hakan; Avlan, Dincer; Bahadir, Gokhan Berktug; Delibaş, Ali; Nayci, Ali

    2016-01-01

    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. PMID:27286115

  14. Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells.

    PubMed

    Sun, Guojun; Zhang, Shuqin; Xie, Yanru; Zhang, Ziyu; Zhao, Wenjing

    2016-01-01

    Gallic acid (3,4,5-trihydroxybenzoic acid; GA) is a naturally occurring plant polyphenol, isolated from water caltrop, which has been reported to exert anticancer effects. The present study investigated the antiproliferative effects of GA on the HepG2 and SMMC-7721 human hepatocellular carcinoma (HCC) cell lines using MTT and colony formation assays. In particular, the underlying mechanism of GA-induced apoptosis in SMMC-7721 cells was studied in vitro by flow cytometry and western blotting. The results of the present study indicated that GA was capable of inhibiting the proliferation of HepG2 and SMMC-7721 cells in a time- and dose-dependent manner, as well as inducing the apoptosis of SMMC-7721 cells. GA induced caspase-3, caspase-9 and reactive oxygen species activity, elevated the expression of apoptosis regulator Bcl-2-like protein 4 and reduced the mitochondrial membrane potential in SMMC-7721 cells. When compared with HL-7702 normal human hepatocytes, GA demonstrated selective toxicity for HCC cells. In conclusion, GA is able to induce apoptosis in SMMC-7721 cells in vitro via mitochondrial-mediated pathways, and may possess the potential to be a novel therapeutic compound for use in the treatment of HCC.

  15. Magnetically directed poly(lactic acid) [sup 90]Y-microspheres: Novel agents for targeted intracavitary radiotherapy

    SciTech Connect

    Haefeli, U.O.; Sweeney, S.M.; Beresford, B.A.; Sim, E.H.; Macklis, R.M. . Joint Center for Radiation Therapy)

    1994-08-01

    High energy [beta]-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. The authors developed as carriers for the ionic form of [sup 90]Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe[sub 3]O[sub 4] which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10--40 [mu]m MMS were radiochemically loaded to high specific activity with [sup 90]Y at a pH of 5.7. Stability studies showed that approximately 95% of added [sup 90]Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. The authors are currently optimizing this system for use in the treatment of neoplastic meningitis.

  16. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation.

    PubMed

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-05-20

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method.

  17. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-05-01

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method.

  18. Reducing-Agent-Free Instant Synthesis of Carbon-Supported Pd Catalysts in a Green Leidenfrost Droplet Reactor and Catalytic Activity in Formic Acid Dehydrogenation

    PubMed Central

    Lee, Dong-Wook; Jin, Min-Ho; Lee, Young-Joo; Park, Ju-Hyoung; Lee, Chun-Boo; Park, Jong-Soo

    2016-01-01

    The development of green synthesis methods for supported noble metal catalysts remains important challenges to improve their sustainability. Here we first synthesized carbon-supported Pd catalysts in a green Leidenfrost droplet reactor without reducing agents, high-temperature calcination and reduction procedures. When the aqueous solution containing Pd nitrate precursor, carbon support, and water is dripped on a hot plate, vapor layer is formed between a solution droplet and hot surface, which allow the solution droplet to be levitated on the hot surface (Leidenfrost phenomena). Subsequently, Pd nanoparticles can be prepared without reducing agents in a weakly basic droplet reactor created by the Leidenfrost phenomena, and then the as-prepared Pd nanoparticles are loaded on carbon supports during boiling down the droplet on hot surface. Compared to conventional incipient wetness and chemical synthetic methods, the Leidenfrost droplet reactor does not need energy-consuming, time-consuming, and environmentally unfriendly procedures, which leads to much shorter synthesis time, lower carbon dioxide emission, and more ecofriendly process in comparison with conventional synthesis methods. Moreover, the catalysts synthesized in the Leidenfrost droplet reactor provided much better catalytic activity for room-temperature formic acid decomposition than those prepared by the incipient wetness method. PMID:27198855

  19. Facile and controllable preparation of mesoporous TiO2 using poly(ethylene glycol) as structure-directing agent and peroxotitanic acid as precursor

    NASA Astrophysics Data System (ADS)

    Nguyen, Dongthanh; Wang, Wei; Long, Haibo; Ru, Hongqiang

    2016-09-01

    This work demonstrated that mesoporous TiO2 (meso-TiO2) with controllable mesoporous and crystalline structures can be facilely prepared by using poly (ethylene glycol) (PEG) as structure-directing (SD) agent and peroxotitanic acid (PTA) as precursor. Meso-TiO2 with high specific surface area (157 m2•g-1), pore volume (0.45 cm3•g-1) and large mesopore size of 13.9 nm can be obtained after calcination at 450°C. Such meso-TiO2 also shows relatively high thermal stability. BET surface area still reaches 114 m2•g-1 after calcination at 550°C. In the synthesis and calcination process, PEG that plays multiple and important roles in delivering thermally stable and tunable mesoporous and crystalline structures shows to be a suitable low-cost SD agent for the controllable preparation of nanocrystalline meso-TiO2. The photocatalytic activity tests show that both high surface area and bi-crystallinity of obtained meso-TiO2 are important in enhancing the performance in photo-decomposing Rhodamine B in water.

  20. The histone deacetylase inhibitor and chemotherapeutic agent suberoylanilide hydroxamic acid (SAHA) induces a cell-death pathway characterized by cleavage of Bid and production of reactive oxygen species

    PubMed Central

    Ruefli, Astrid A.; Ausserlechner, Michael J.; Bernhard, David; Sutton, Vivien R.; Tainton, Kellie M.; Kofler, Reinhard; Smyth, Mark J.; Johnstone, Ricky W.

    2001-01-01

    Many chemotherapeutic agents induce mitochondrial-membrane disruption to initiate apoptosis. However, the upstream events leading to drug-induced mitochondrial perturbation have remained poorly defined. We have used a variety of physiological and pharmacological inhibitors of distinct apoptotic pathways to analyze the manner by which suberoylanilide hydroxamic acid (SAHA), a chemotherapeutic agent and histone deacetylase inhibitor, induces cell death. We demonstrate that SAHA initiates cell death by inducing mitochondria-mediated death pathways characterized by cytochrome c release and the production of reactive oxygen species, and does not require the activation of key caspases such as caspase-8 or -3. We provide evidence that mitochondrial disruption is achieved by means of the cleavage of the BH3-only proapoptotic Bcl-2 family member Bid. SAHA-induced Bid cleavage was not blocked by caspase inhibitors or the overexpression of Bcl-2 but did require the transcriptional regulatory activity of SAHA. These data provide evidence of a mechanism of cell death mediated by transcriptional events that result in the cleavage of Bid, disruption of the mitochondrial membrane, and production of reactive oxygen species to induce cell death. PMID:11535817

  1. 18β-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents.

    PubMed

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

    2016-04-22

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

  2. Effect of silanecoupling agent on properties of biocomposites based on poly(lactic acid)and durian rind cellulose

    NASA Astrophysics Data System (ADS)

    Penjumras, P.; AbdulRahman, R.; Talib, R. A.; Abdan, K.

    2016-07-01

    Durian rind cellulose reinforced poly(lactic acid) (PLA) biocomposites were prepared using Brabender internal mixer followed by hot compression molding technique. Cellulose was previously treated by 3-aminopropyltriethoxysilane for improving the compatibility with PLA matrix. The silane-grafting of cellulose was confirmed via Fourier transform infrared spectroscopy (FTIR) with the presence of Si-O-Si, Si-C, and Si-O-C bonds. The silane-treated cellulose was subsequently introduced into PLA matrix, and the effects of cellulose surface modification on mechanical, thermal and morphological properties, and water absorption of biocomposites were studied. It was found that silane-treated cellulose reinforced biocompositeshave superior mechanical properties compared with untreated cellulose reinforced biocomposites. The lowest crystallization temperature of silane-treated biocomposites was confirmed via Differential scanning calorimetry (DSC). Scanning electron microscopy (SEM) investigation also showed that adhesion of cellulose and PLA matrix was improved by modification of cellulosesurfaceusing3-aminopropyltriethoxysilanewhich can result in less water absorption into biocomposites.

  3. Caffeic acid phenethyl ester as a remedial agent for reproductive functions and oxidative stress-based pathologies of gonads

    PubMed Central

    Akyol, Sumeyya; Akbas, Ali; Butun, Ilknur; Toktas, Muhsin; Ozyurt, Huseyin; Sahin, Semsettin; Akyol, Omer

    2015-01-01

    In recent years, the studies on the roles of caffeic acid phenethyl ester (CAPE) in several disease models and cell cultures are tremendously growing. It is such a great molecule that was used by ancient times to ameliorate some diseases and nowadays, it is used by modern medicine to test the effectiveness. In this mini-review article, the protection capability of CAPE, as a liposoluble antioxidant and a potent nuclear factor kappa B inhibitor, on oxidative and non-oxidative ovary, and testis damages has been summarized. In view of our laboratory findings/experience and those reported in the hitherto literature, we suggest that CAPE possesses protective effects for pathologies of the reproductive organs induced by untoward effects of harmful molecules such as free oxygen radicals, pesticides, methotrexate, and MK-801 (dizocilpine). PMID:26401405

  4. Caffeic acid phenethyl ester as a protective agent against nephrotoxicity and/or oxidative kidney damage: a detailed systematic review.

    PubMed

    Akyol, Sumeyya; Ugurcu, Veli; Altuntas, Aynur; Hasgul, Rukiye; Cakmak, Ozlem; Akyol, Omer

    2014-01-01

    Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility.

  5. Cultivable microbiota of Lithobates catesbeianus and advances in the selection of lactic acid bacteria as biological control agents in raniculture.

    PubMed

    Mendoza, Gabriela Montel; Pasteris, Sergio E; Ale, Cesar E; Otero, María C; Bühler, Marta I; Nader-Macías, María E Fátima

    2012-12-01

    The cultivable microbiota of skin and cloaca of captive Lithobates catesbeianus includes microorganisms generally accepted as beneficial and potentially pathogenic bacteria. In order to select a group of potentially probiotic bacteria, 136 isolates were evaluated for their surface properties and production of antagonistic metabolites. Then, 11 lactic acid bacteria (LAB) strains were selected and identified as Lactobacillus plantarum, Lb. brevis, Pediococcus pentosaceus, Lactococcus lactis, L. garvieae and Enterococcus gallinarum. Studies of compatibility indicate that all the strains could be included in a multi-strain probiotic, with the exception of Ent. gallinarum CRL 1826 which inhibited LAB species through a bacteriocin-like metabolite. These results contribute to the design of a probiotic product to improve the sanitary status of bullfrogs in intensive culture systems, to avoid the use of antibiotics and thus to reduce production costs. It could also be an alternative to prevent infectious diseases during the ex situ breeding of amphibian species under threat of extinction.

  6. Caffeic acid phenethyl ester as a remedial agent for reproductive functions and oxidative stress-based pathologies of gonads.

    PubMed

    Akyol, Sumeyya; Akbas, Ali; Butun, Ilknur; Toktas, Muhsin; Ozyurt, Huseyin; Sahin, Semsettin; Akyol, Omer

    2015-01-01

    In recent years, the studies on the roles of caffeic acid phenethyl ester (CAPE) in several disease models and cell cultures are tremendously growing. It is such a great molecule that was used by ancient times to ameliorate some diseases and nowadays, it is used by modern medicine to test the effectiveness. In this mini-review article, the protection capability of CAPE, as a liposoluble antioxidant and a potent nuclear factor kappa B inhibitor, on oxidative and non-oxidative ovary, and testis damages has been summarized. In view of our laboratory findings/experience and those reported in the hitherto literature, we suggest that CAPE possesses protective effects for pathologies of the reproductive organs induced by untoward effects of harmful molecules such as free oxygen radicals, pesticides, methotrexate, and MK-801 (dizocilpine).

  7. Caffeic Acid Phenethyl Ester as a Protective Agent against Nephrotoxicity and/or Oxidative Kidney Damage: A Detailed Systematic Review

    PubMed Central

    Akyol, Sumeyya; Ugurcu, Veli; Altuntas, Aynur; Hasgul, Rukiye; Cakmak, Ozlem

    2014-01-01

    Caffeic acid phenethyl ester (CAPE), an active component of propolis, has been attracting the attention of different medical and pharmaceutical disciplines in recent years because of its antioxidant, anti-inflammatory, antiproliferative, cytotoxic, antiviral, antifungal, and antineoplastic properties. One of the most studied organs for the effects of CAPE is the kidney, particularly in the capacity of this ester to decrease the nephrotoxicity induced by several drugs and the oxidative injury after ischemia/reperfusion (I/R). In this review, we summarized and critically evaluated the current knowledge regarding the protective effect of CAPE in nephrotoxicity induced by several special medicines such as cisplatin, doxorubicin, cyclosporine, gentamycin, methotrexate, and other causes leading to oxidative renal injury, namely, I/R models and senility. PMID:25003138

  8. Sustained release of anticancer agent phytic acid from its chitosan-coated magnetic nanoparticles for drug-delivery system

    PubMed Central

    Barahuie, Farahnaz; Dorniani, Dena; Saifullah, Bullo; Gothai, Sivapragasam; Hussein, Mohd Zobir; Pandurangan, Ashok Kumar; Arulselvan, Palanisamy; Norhaizan, Mohd Esa

    2017-01-01

    Chitosan (CS) iron oxide magnetic nanoparticles (MNPs) were coated with phytic acid (PTA) to form phytic acid-chitosan-iron oxide nanocomposite (PTA-CS-MNP). The obtained nanocomposite and nanocarrier were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, vibrating sample magnetometry, transmission electron microscopy, and thermogravimetric and differential thermogravimetric analyses. Fourier transform infrared spectra and thermal analysis of MNPs and PTA-CS-MNP nanocomposite confirmed the binding of CS on the surface of MNPs and the loading of PTA in the PTA-CS-MNP nanocomposite. The coating process enhanced the thermal stability of the anticancer nanocomposite obtained. X-ray diffraction results showed that the MNPs and PTA-CS-MNP nanocomposite are pure magnetite. Drug loading was estimated using ultraviolet-visible spectroscopy and showing a 12.9% in the designed nanocomposite. Magnetization curves demonstrated that the synthesized MNPs and nanocomposite were superparamagnetic with saturation magnetizations of 53.25 emu/g and 42.15 emu/g, respectively. The release study showed that around 86% and 93% of PTA from PTA-CS-MNP nanocomposite could be released within 127 and 56 hours by a phosphate buffer solution at pH 7.4 and 4.8, respectively, in a sustained manner and governed by pseudo-second order kinetic model. The cytotoxicity of the compounds on HT-29 colon cancer cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The HT-29 cell line was more sensitive against PTA-CS-MNP nanocomposite than PTA alone. No cytotoxic effect was observed on normal cells (3T3 fibroblast cells). This result indicates that PTA-CS-MNP nanocomposite can inhibit the proliferation of colon cancer cells without causing any harm to normal cell. PMID:28392693

  9. Non-surgical treatment of deep wounds triggered by harmful physical and chemical agents: a successful combined use of collagenase and hyaluronic acid.

    PubMed

    Onesti, Maria G; Fino, Pasquale; Ponzo, Ida; Ruggieri, Martina; Scuderi, Nicolò

    2016-02-01

    Some chronic ulcers often occur with slough, not progressing through the normal stages of wound healing. Treatment is long and other therapies need to be performed in addition to surgery. Patients not eligible for surgery because of ASA class (American Society of Anesthesiologists class) appear to benefit from chemical therapy with collagenase or hydrocolloids in order to prepare the wound bed, promoting the healing process. We describe four cases of traumatic, upper limb deep wounds caused by different physical and chemical agents, emphasising the effectiveness of treatment based on topical application of collagenase and hyaluronic acid (HA) before standardised surgical procedures. We performed careful disinfection of lesions combined with application of topical cream containing hyaluronic acid, bacterial fermented sodium hyaluronate (0·2%w/w) salt, and bacterial collagenase obtained from non-pathogenic Vibrio alginolyticus (>2·0 nkat1/g). In one patient a dermo-epidermal graft was used to cover the wide loss of substance. In two patients application of a HA-based dermal substitute was done. We obtained successful results in terms of wound healing, with satisfactory aesthetic result and optimal recovery of the affected limb functionality. Topical application of collagenase and HA, alone or before standardised surgical procedures allows faster wound healing.

  10. Design, Synthesis, and Evaluation of 1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic Acid-Derived, Redox-Sensitive Contrast Agents for Magnetic Resonance Imaging

    PubMed Central

    Raghunand, Natarajan; Guntle, Gerald P.; Gokhale, Vijay; Nichol, Gary S.; Mash, Eugene A.; Jagadish, Bhumasamudram

    2010-01-01

    The design and synthesis of three 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivatives bearing linkers with terminal thiol groups and a preliminary evaluation of their potential for use in assembling redox-sensitive Magnetic Resonance Imaging (MRI) contrast agents are reported. The linkers were selected based on computational docking with a crystal structure of human serum albumin (HSA). Gd(III)-DO3A and Eu(III)-DO3A complexes were synthesized, and the structure of one complex was established by X-ray crystallographic analysis. The binding to HSA of a Gd(III)-DO3A complex bearing a thiol-terminated 3,6-dioxanonyl chain was competitively inhibited by homocysteine and by the corresponding Eu chelate. Binding to HSA was abolished when the terminal thiol group of this complex was absent. The longitudinal water-proton relaxivities (r1) of the three Gd(III)-DO3A complexes and of two Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexes were measured in saline at 7 Tesla. The DO3A complexes exhibited smaller r1 values, in both bound and free states, than the DOTA complexes. PMID:20722424

  11. Poly(ornithine-co-arginine-co-glycine-co-aspartic Acid): Preparation via NCA Polymerization and its Potential as a Polymeric Tumor-Penetrating Agent.

    PubMed

    Yu, Haiyang; Tang, Zhaohui; Zhang, Dawei; Song, Wantong; Duan, Taicheng; Gu, Jingkai; Chen, Xuesi

    2015-06-01

    A novel random copolypeptide of ornithine, arginine, glycine, and aspartic acid [Poly(ornithine-co-arginine-co-glycine-co-aspartic acid), Poly(O,R,G,D)] has been prepared through ring-opening polymerization of N-δ-carbobenzoxy-l-ornithine N-carboxyanhydride [Orn(Cbz)-NCA)], l-glycine N-carboxyanhydride (Gly-NCA) and β-benzyl l-aspartate N-carboxyanhydride [Asp(Bn)-NCA], following by subsequent deprotection and guanidization. The structure of Poly(O,R,G,D) was confirmed by nuclear magnetic resonance (NMR) spectroscopy and gel permeation chromatography (GPC). Low cytotoxicity of Poly(O,R,G,D) was confirmed from MTT assay. The Poly(O,R,G,D) contain some internal sequences of RXXR (X = O, R, G, or D) that could be proteolytically cleaved to expose the cryptic CendR element and bind to Neuropilin-1. This would lead to vascular and tissue permeabilization. Therefore trypsin-cleaved Poly(O,R,G,D) increase the vascular leakage of Evans blue from dermal microvessels at the injection site in vivo skin permeability assay. The intratumoral injection of the Poly(O,R,G,D) significantly enhanced the concentration of cisplatin-loaded nanoparticles in MCF-7 solid tumors. These results show that Poly(O,R,G,D) could increase the vascular leakage and tissue penetration of nanoparticles in a solid tumor and can be used as a potential polymeric tumor-penetrating agent.

  12. Immune activity and biodistribution of polypeptide K237 and folic acid conjugated amphiphilic PEG-PLGA copolymer nanoparticles radiolabeled with 99mTc

    PubMed Central

    Wu, Yufeng; Huang, Xuanzhang; Chen, Jie; Xia, Junyong; Jiang, Hao; Ma, Jing; Wu, Jian

    2016-01-01

    In a previous study, amphiphilic copolymer, polypeptide K237 (HTMYYHHYQHHL) and folic acid (FA) modified poly(ethylene glycol)-poly(lactic-co-glycolic acid) (K237/FA-PEG-PLGA) nanoparticles were developed and studied as a drug carrier. To further promote the clinical application of K237/FA-PEG-PLGA nanoparticles and provide guidance for future research, we need to examine their specific biodistribution in vivo. In this study, K237/FA-PEG-PLGA nanoparticles were effectively labeled by a direct method with Technetium-99m (99mTc) using stannous chloride as a reducing agent. The optimal stability of the labeled nanoparticles was determined by evaluating their radiochemical purity in serum, physiological saline, diethylenetriaminepentaacetic acid (DTPA) and cysteine solutions. The affinity of ligands and receptors was elicited by cell binding and blocking experiments in KDR/folate receptor high expressing SKOV-3 ovarian cancer cells. The nanoparticles biodistribution was studied after intravenous administration in healthy mice xenografted with SKOV-3 cells. A higher percent injected dose per gram of tissue (% ID/g) was observed in liver, kidney, spleen, blood and tumor at 3 and 9 h post-injection. Scintigraphic images revealed that the radioactivity was mainly concentrated in tumor, liver, kidney and bladder; and in the heart, lung, and muscle was significantly lower at 3 h. The radioactivity distribution in the images is consistent with the in vivo biodistribution data. Our works demonstrated that K237/FA-PEG-PLGA nanoparticles have great potential as biodegradable drug carriers, especially for tumors expressing the folate and KDr receptor. PMID:27791199

  13. Intracellular delivery of the reactive oxygen species generating agent D-penicillamine upon conjugation to poly-L-glutamic acid.

    PubMed

    Wadhwa, Saurabh; Mumper, Russell J

    2010-06-07

    D-penicillamine is an aminothiol that is cytotoxic to cancer cells and generates dose dependent reactive oxygen species (ROS) via copper catalyzed oxidation. However, the delivery of D-pen to cancer cells remains a challenge due to its high hydrophilicity, highly reactive thiol group and impermeability to the cell membrane. To overcome this challenge, we investigated a novel poly-L-glutamic acid (PGA) conjugate of D-pen (PGA-D-pen) where D-pen was conjugated to PGA modified with 2-(2-pyridyldithio)-ethylamine (PDE) via disulfide bonds. Confocal microscopy and cell uptake studies showed that the fluorescently labeled PGA-D-pen was taken up by human leukemia cells (HL-60) in a time dependent manner. Treatment of HL-60, murine leukemia cells (P388) and human breast cancer cells (MDA-MB-468) with PGA-D-pen resulted in dose dependent cytotoxicity and elevation of intracellular ROS levels. PGA-D-pen induced apoptosis in HL-60 cells which was verified by Annexin V binding. The in vivo evaluation of the conjugate in the P388 murine leukemia model (intraperitoneal) resulted in significant enhancement in the survival of CD2F1 mice over vehicle control.

  14. Effects of dosmalfate, a new cytoprotective agent, on acute and chronic trinitrobenzene sulphonic acid-induced colitis in rats.

    PubMed

    Villegas, Isabel; La Casa, Carmen; Orjales, Aurelio; Alarcón de la Lastra, Catalina

    2003-01-24

    Activated neutrophils and proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha) are clearly involved in the pathogenesis of bowel disease. Increased expression of epidermal growth factor-receptor (EGF receptor) has been reported for the colon mucosa surrounding areas of ulceration, suggesting a pivotal role in mucosal defence and repair. In this study, we examined the effects of dosmalfate, a new flavonoid derivative compound (diosmin heptakis) with antioxidant and cytoprotective properties, on acute and chronic experimental trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. The inflammation response was assessed by neutrophil infiltration as evaluated by histology and myeloperoxidase activity. Mucosal TNF-alpha production and histological analysis of the lesions was also carried out. In addition, we studied the expression of the EGF receptor inmunohistochemically during the healing of TNBS-induced chronic colitis. A 2-day treatment with 400 or 800 mg/kg of dosmalfate ameliorated the colon damage score and the incidence of adhesions. It also significantly (P<0.05) decreased myeloperoxidase activity and colonic mucosal production of TNF-alpha. Chronic treatment (14 days) with 800 mg/kg/day of dosmalfate also had significant protective effects on TNBS-induced colitis which were reflected by significant attenuation (P<0.05) of the damage score while the inflammatory indicators were not improved. The chronic beneficial effect of dosmalfate was apparently related to the enhancement of EGF receptor expression. These findings confirm the protective effects of dosmalfate in acute and chronic experimental colitis.

  15. Qualitative environmental risk assessment of photolytic transformation products of iodinated X-ray contrast agent diatrizoic acid.

    PubMed

    Rastogi, Tushar; Leder, Christoph; Kümmerer, Klaus

    2014-06-01

    Recent studies have confirmed that the aquatic ecosystem is being polluted with an unknown cocktail of pharmaceuticals, their metabolites and/or their transformation products (TPs). Although individual chemicals are typically present at low concentrations, they can interact with each other resulting in additive or potentially even synergistic mixture effects. Therefore it is necessary to assess the environmental risk caused by these chemicals. Data on exposure is required for quantitative risk assessment of TPs and/or metabolites. Such data are mostly missing because of the non-availability of TPs and very often metabolites for experimental testing. This study demonstrates the application of different in silico tools for qualitative risk assessment using the example of photodegradation TPs (photo-TPs) of diatrizoic acid (DIAT), which itself is not readily biodegradable. Its photolytic transformation was studied and the photodegradation pathway was established. The aerobic biodegradability of photo-TPs under the conditions of an aquatic environment was assessed using standardized OECD tests. The qualitative risk assessment of DIAT and selected photo-TPs was performed by the PBT approach (i.e. Persistence, Bioaccumulation and Toxicity), using experimental biodegradation test assays, applying different QSAR models with several different toxicological endpoints and in silico read-across approaches. The qualitative risk assessment pointed out that the photo-TPs were less persistent compared to DIAT and none of them possessed any bioaccumulation threat. However, a few photo-TPs were predicted to be active for mutagenicity and genotoxicity, which indicate the need for further testing to confirm these predictions. The present study demonstrates that in silico qualitative risk assessment analysis can increase the knowledge space about the environmental fate of TPs.

  16. Metal Zn(II), Cu(II), Ni (II) complexes of ursodeoxycholic acid as putative anticancer agents

    PubMed Central

    Dyakova, Lora; Culita, Daniela-Cristina; Marinescu, Gabriela; Alexandrov, Marin; Kalfin, Reni; Patron, Luminita; Alexandrova, Radostina

    2014-01-01

    The aim of the study was to evaluate the influence of metal [Zn(II), Cu(II), Ni(II)] complexes with ursodeoxycholic acid (UDCA) on the viability and proliferation of tumour and non-tumour cells. Cell lines established from retrovirus-transformed chicken hepatoma (LSCC-SF-Mc29) and rat sarcoma (LSR-SF-SR) as well as from human cancers of the breast (MCF-7), uterine cervix (HeLa), lung (A549) and liver (HepG2) were used as model systems. Non-tumour human embryo (Lep-3) cells were also included in some of the experiments. The investigations were carried out by the thiazolyl blue tetrazolium bromide (MTT) test, neutral red uptake cytotoxicity assay, crystal violet staining, double staining with acridine orange and propidium iodide and the colony-forming method. The results obtained revealed that: (1) UDCA and its metal complexes in the tested concentrations decreased (to a varying degree) the viability and proliferation of the treated cells in a time- and concentration-dependent manner; (2) chicken hepatoma (LSCC-SF-Mc29) cells were most sensitive to the cytotoxic and antiproliferative action of the compounds tested, followed by rat sarcoma (LSR-SF-SR) cells; (3) Cu‒UDCA and Ni‒UDCA were more effective against animal LSCC-SF-Mc29 and LSR-SF-SR cells, while Zn‒UDCA significantly decreased the viability and proliferation of human tumour cell lines; (4) applied independently, UDCA expressed lower cytotoxic/cytostatic activity as compared to metal complexes; and (5) the sensitivity of the non-tumour embryonic Lep-3 cells to the effects of UDCA and its metal complexes was comparable or even higher than those of the human tumour cells. PMID:26019542

  17. Assessment of Tumor Response to the Vascular Disrupting Agents 5,6-Dimethylxanthenone-4-Acetic Acid or Combretastatin-A4-Phosphate by Intrinsic Susceptibility Magnetic Resonance Imaging

    SciTech Connect

    McPhail, Lesley D. Griffiths, John R. D.Phil.; Robinson, Simon P.

    2007-11-15

    Purpose: To investigate the use of the transverse magnetic resonance imaging (MRI) relaxation rate R{sub 2}* (s{sup -1}) as a biomarker of tumor vascular response to monitor vascular disrupting agent (VDA) therapy. Methods and Materials: Multigradient echo MRI was used to quantify R{sub 2}* in rat GH3 prolactinomas. R{sub 2}* is a sensitive index of deoxyhemoglobin in the blood and can therefore be used to give an index of tissue oxygenation. Tumor R{sub 2}* was measured before and up to 35 min after treatment, and 24 h after treatment with either 350 mg/kg 5,6-dimethylxanthenone-4-acetic acid (DMXAA) or 100 mg/kg combretastatin-A4-phosphate (CA4P). After acquisition of the MRI data, functional tumor blood vessels remaining after VDA treatment were quantified using fluorescence microscopy of the perfusion marker Hoechst 33342. Results: DMXAA induced a transient, significant (p < 0.05) increase in tumor R{sub 2}* 7 min after treatment, whereas CA4P induced no significant changes in tumor R{sub 2}* over the first 35 min. Twenty-four hours after treatment, some DMXAA-treated tumors demonstrated a decrease in R{sub 2}*, but overall, reduction in R{sub 2}* was not significant for this cohort. Tumors treated with CA4P showed a significant (p < 0.05) reduction in R{sub 2}* 24 h after treatment. The degree of Hoechst 33342 uptake was associated with the degree of R{sub 2}* reduction at 24 h for both agents. Conclusions: The reduction in tumor R{sub 2}* or deoxyhemoglobin levels 24 h after VDA treatment was a result of reduced blood volume caused by prolonged vascular collapse. Our results suggest that DMXAA was less effective than CA4P in this rat tumor model.

  18. Inhibitory effects of retinoic acid metabolism blocking agents (RAMBAs) on the growth of human prostate cancer cells and LNCaP prostate tumour xenografts in SCID mice

    PubMed Central

    Huynh, C K; Brodie, A M H; Njar, V C O

    2006-01-01

    In recent studies, we have identified several highly potent all-trans-retinoic acid (ATRA) metabolism blocking agents (RAMBAs). On the basis of previous effects of liarozole (a first-generation RAMBA) on the catabolism of ATRA and on growth of rat Dunning R3227G prostate tumours, we assessed the effects of our novel RAMBAs on human prostate tumour (PCA) cell lines. We examined three different PCA cell lines to determine their capacity to induce P450-mediated oxidation of ATRA. Among the three different cell lines, enhanced catabolism was detected in LNCaP, whereas it was not found in PC-3 and DU-145. This catabolism was strongly inhibited by our RAMBAs, the most potent being VN/14-1, VN/50-1, VN/66-1, and VN/69-1 with IC50 values of 6.5, 90.0, 62.5, and 90.0 nM, respectively. The RAMBAs inhibited the growth of LNCaP cells with IC50 values in the μM-range. In LNCaP cell proliferation assays, VN/14-1, VN/50-1, VN/66-1, and VN/69-1 also enhanced by 47-, 60-, 70-, and 65-fold, respectively, the ATRA-mediated antiproliferative activity. We then examined the molecular mechanism underlying the growth inhibitory properties of ATRA alone and in combination with RAMBAs. The mechanism appeared to involve the induction of differentiation, cell-cycle arrest, and induction of apoptosis (TUNEL), involving increase in Bad expression and decrease in Bcl-2 expression. Treatment of LNCaP tumours growing in SCID mice with VN/66-1 and VN/69-1 resulted in modest but statistically significant tumour growth inhibition of 44 and 47%, respectively, while treatment with VN/14-1 was unexpectedly ineffective. These results suggest that some of our novel RAMBAs may be useful agents for the treatment of prostate cancer. PMID:16449997

  19. Potent and sustained cellular inhibition of miR-122 by lysine-derivatized peptide nucleic acids (PNA) and phosphorothioate locked nucleic acid (LNA)/2'-O-methyl (OMe) mixmer anti-miRs in the absence of transfection agents

    PubMed Central

    Torres, Adrian G.; Threlfall, Richard N.

    2011-01-01

    Efficient cell delivery of antisense oligonucleotides (ONs) is a key issue for their potential therapeutic use. It has been shown recently that some ONs can be delivered into cells without the use of transfection agents (gymnosis), but this generally requires cell incubation over several days and high amounts of ONs (micromolar concentrations). Here we have targeted microRNA 122 (miR-122), a small non-coding RNA involved in regulation of lipid metabolism and in the replication of hepatitis C virus, with ONs of different chemistries (anti-miRs) by gymnotic delivery in cell culture. Using a sensitive dual-luciferase reporter assay, anti-miRs were screened for their ability to enter liver cells gymnotically and inhibit miR-122 activity. Efficient miR-122 inhibition was obtained with cationic PNAs and 2'-O-methyl (OMe) and Locked Nucleic Acids (LNA)/OMe mixmers containing either phosphodiester (PO) or phosphorothioate (PS) linkages at sub-micromolar concentrations when incubated with cells for just 4 hours. Furthermore, PNA and PS-containing anti-miRs were able to sustain miR-122 inhibitory effects for at least 4 days. LNA/OMe PS anti-miRs were the most potent anti-miR chemistry tested in this study, an ON chemistry that has been little exploited so far as anti-miR agents towards therapeutics. PMID:22567190

  20. Gd(DOTAla): a single amino acid Gd-complex as a modular tool for high relaxivity MR contrast agent development.

    PubMed

    Boros, Eszter; Polasek, Miloslav; Zhang, Zhaoda; Caravan, Peter

    2012-12-05

    MR imaging at high magnetic fields benefits from an increased signal-to-noise ratio; however T(1)-based MR contrast agents show decreasing relaxivity (r(1)) at higher fields. High field, high relaxivity contrast agents can be designed by carefully controlling the rotational dynamics of the molecule. To this end, we investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc-protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures. Gd(III) coordination results in very rigid attachment of the metal chelate to the peptide backbone through both the amino acid side chain and coordination of the amide carbonyl. Linear and cyclic monomers (GdL1, GdC1), dimers (Gd(2)L2, Gd(2)C2), and trimers (Gd(3)L3, Gd(3)C3) were prepared and relaxivities were determined at different field strengths ranging from 0.47 to 11.7 T. Amide carbonyl coordination was indirectly confirmed by determination of the hydration number q for the EuL1 integrated into a peptide backbone, q = 0.96 ± 0.09. The water residency time of GdL1 at 37 °C was optimal for relaxivity, τ(M) = 17 ± 2 ns. Increased molecular size leads to increased per Gd relaxivity (from r(1) = 7.5 for GdL1 to 12.9 mM(-1) s(-1) for Gd(3)L3 at 1.4 T, 37 °C). The cyclic, multimeric derivatives exhibited slightly higher relaxivities than the corresponding linearized multimers (Gd(2)C2: r(1) = 10.5 mM(-1) s(-1) versus Gd(2)C2-red r(1) = 9 mM(-1) s(-1) at 1.4 T, 37 °C). Overall, all six synthesized Gd complexes had higher relaxivities at low, intermediate, and high fields than the clinically used small molecule contrast agent [Gd(HP-DO3A)(H(2)O)].

  1. Gd(DOTAla) – A single amino acid Gd-complex as a modular tool for high relaxivity MR contrast agent development

    PubMed Central

    Boros, Eszter; Polasek, Miloslav; Zhang, Zhaoda; Caravan, Peter

    2012-01-01

    MR imaging at high magnetic fields benefits from an increased signal to noise ratio, however T1 based MR contrast agents show decreasing relaxivity (r1) at higher fields. High field, high relaxivity contrast agents can be designed by carefully controlling the rotational dynamics of the molecule. To this end, we investigated applications of the alanine analogue of Gd(DOTA), Gd(DOTAla). Fmoc protected DOTAla suitable for solid phase peptide synthesis was synthesized and integrated into polypeptide structures. Gd(III) coordination results in very rigid attachment of the metal chelate to the peptide backbone through both the amino acid sidechain and coordination of the amide carbonyl. Linear and cyclic monomers (GdL1, GdC1), dimers (Gd2L2, Gd2C2) and trimers (Gd3L3, Gd3C3) were prepared and relaxivities were determined at different field strengths ranging from 0.47T to 11.7T. Amide carbonyl coordination was indirectly confirmed by determination of the hydration number q for the EuL1 integrated into a peptide backbone, q = 0.96±0.09. The water residency time of GdL1 at 37 °C was optimal for relaxivity, τM=17±2 ns. Increased molecular size leads to increased per Gd relaxivity (from r1 = 7.5 for GdL1 to 12.9 mM−1s−1 for Gd3L3 at 1.4T, 37 °C). The cyclic, multimeric derivatives exhibited slightly higher relaxivities than the corresponding linearized multimers (Gd2C2: r1 = 10.5 mM−1 s−1 versus Gd2C2-red r1 = 9 mM−1s−1 at 1.4T, 37 °C). Overall, all six synthesized Gd complexes had higher relaxivities at low, intermediate and high fields than the clinically used small molecule contrast agent [Gd(HP-DO3A)(H2O)]. PMID:23157602

  2. Design, synthesis, and biological evaluation of water-soluble amino acid prodrug conjugates derived from combretastatin, dihydronaphthalene, and benzosuberene-based parent vascular disrupting agents.

    PubMed

    Devkota, Laxman; Lin, Chen-Ming; Strecker, Tracy E; Wang, Yifan; Tidmore, Justin K; Chen, Zhi; Guddneppanavar, Rajsekhar; Jelinek, Christopher J; Lopez, Ramona; Liu, Li; Hamel, Ernest; Mason, Ralph P; Chaplin, David J; Trawick, Mary Lynn; Pinney, Kevin G

    2016-03-01

    Targeting tumor vasculature represents an intriguing therapeutic strategy in the treatment of cancer. In an effort to discover new vascular disrupting agents with improved water solubility and potentially greater bioavailability, various amino acid prodrug conjugates (AAPCs) of potent amino combretastatin, amino dihydronaphthalene, and amino benzosuberene analogs were synthesized along with their corresponding water-soluble hydrochloride salts. These compounds were evaluated for their ability to inhibit tubulin polymerization and for their cytotoxicity against selected human cancer cell lines. The amino-based parent anticancer agents 7, 8, 32 (also referred to as KGP05) and 33 (also referred to as KGP156) demonstrated potent cytotoxicity (GI50=0.11-40nM) across all evaluated cell lines, and they were strong inhibitors of tubulin polymerization (IC50=0.62-1.5μM). The various prodrug conjugates and their corresponding salts were investigated for cleavage by the enzyme leucine aminopeptidase (LAP). Four of the glycine water-soluble AAPCs (16, 18, 44 and 45) showed quantitative cleavage by LAP, resulting in the release of the highly cytotoxic parent drug, whereas partial cleavage (<10-90%) was observed for other prodrugs (15, 17, 24, 38 and 39). Eight of the nineteen AAPCs (13-16, 42-45) showed significant cytotoxicity against selected human cancer cell lines. The previously reported CA1-diamine analog and its corresponding hydrochloride salt (8 and 10, respectively) caused extensive disruption (at a concentration of 1.0μM) of human umbilical vein endothelial cells growing in a two-dimensional tubular network on matrigel. In addition, compound 10 exhibited pronounced reduction in bioluminescence (greater than 95% compared to saline control) in a tumor bearing (MDA-MB-231-luc) SCID mouse model 2h post treatment (80mg/kg), with similar results observed upon treatment (15mg/kg) with the glycine amino-dihydronaphthalene AAPC (compound 44). Collectively, these results

  3. Retinoic acid conjugates as potential antitumor agents: synthesis and biological activity of conjugates with Ara-A, Ara-C, 3(2H)-furanone, and aniline mustard moieties.

    PubMed

    Manfredini, S; Simoni, D; Ferroni, R; Bazzanini, R; Vertuani, S; Hatse, S; Balzarini, J; De Clercq, E

    1997-11-07

    In a dual targeting approach, to explore the ability of tretinoin (all-trans-retinoic acid) to behave as a covalent carrier for cytotoxic entities, conjugates of retinoic acid with a few representative molecules, being important examples of antitumor pharmacophores (i.e., nucleoside analogues and alkylating agents), have been synthesized and tested for their cytostatic and differentiating activity. All compounds were stable to in vitro hydrolysis in human plasma and more lipophilic than the parent compounds, thus consenting enhanced uptake into the cells. Among the nucleoside analogues the Ara-C derivatives 3 and 6 and the Ara-A derivative 7 proved the most cytostatic (IC50 < 0.32 microgram/mL) resulting from 25- to > 144-fold more active (Ara-A derivatives) or at least as equally active (Ara-C derivatives) as compared to the parent nucleosides. Compound 3, endowed with a highly lipophilic silyl moiety at the 3' and 5' positions, showed the highest differentiating activity (54% and 44% differentiated HL-60 cells at 0.2 and 0.05 microgram/mL respectively). With regard to the retinoic acid conjugates of alkylating agents, compound 10 was the most cytostatic agent (IC50 < 0.32 microgram/mL) and the most potent differentiating agent (33-34% at 0.32 and 0.08 microgram/mL). These structures may also be regarded as analogs of either retinoic acid or the cytotoxic compound.

  4. Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink.

    PubMed

    Wilson, Maxwell Z; Wang, Rurun; Gitai, Zemer; Seyedsayamdost, Mohammad R

    2016-02-09

    While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal-bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA's cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed.

  5. Mode of action and resistance studies unveil new roles for tropodithietic acid as an anticancer agent and the γ-glutamyl cycle as a proton sink

    PubMed Central

    Wilson, Maxwell Z.; Wang, Rurun; Gitai, Zemer; Seyedsayamdost, Mohammad R.

    2016-01-01

    While we have come to appreciate the architectural complexity of microbially synthesized secondary metabolites, far less attention has been paid to linking their structural features with possible modes of action. This is certainly the case with tropodithietic acid (TDA), a broad-spectrum antibiotic generated by marine bacteria that engage in dynamic symbioses with microscopic algae. TDA promotes algal health by killing unwanted marine pathogens; however, its mode of action (MoA) and significance for the survival of an algal–bacterial miniecosystem remains unknown. Using cytological profiling, we herein determine the MoA of TDA and surprisingly find that it acts by a mechanism similar to polyether antibiotics, which are structurally highly divergent. We show that like polyether drugs, TDA collapses the proton motive force by a proton antiport mechanism, in which extracellular protons are exchanged for cytoplasmic cations. The α-carboxy-tropone substructure is ideal for this purpose as the proton can be carried on the carboxyl group, whereas the basicity of the tropylium ion facilitates cation export. Based on similarities to polyether anticancer agents we have further examined TDA’s cytotoxicity and find it to exhibit potent, broad-spectrum anticancer activities. These results highlight the power of MoA-profiling technologies in repurposing old drugs for new targets. In addition, we identify an operon that confers TDA resistance to the producing marine bacteria. Bioinformatic and biochemical analyses of these genes lead to a previously unknown metabolic link between TDA/acid resistance and the γ-glutamyl cycle. The implications of this resistance mechanism in the context of the algal-bacterial symbiosis are discussed. PMID:26802120

  6. Influence of different acid and alkaline cleaning agents on the effects of irrigation of synthetic dairy factory effluent on soil quality, ryegrass growth and nutrient uptake.

    PubMed

    Liu, Y-Y; Haynes, R J

    2013-01-01

    The aim of this study was to examine the effects of replacement of phosphoric acid with nitric or acetic acid, and replacement of NaOH with KOH, as cleaning agents in dairy factories, on the effects that irrigation of dairy factory effluent (DFE) has on the soil-plant system. A 16-week greenhouse study was carried out in which the effects of addition of synthetic dairy factory effluent containing (a) milk residues alone or milk residues plus (b) H(3)PO(4)/NaOH, (c) H(3)PO(4)/HNO(3)/NaOH or (d) CH(3)COOH/KOH, on soil's chemical, physical and microbial properties and perennial ryegrass growth and nutrient uptake were investigated. The cumulative effect of DFE addition was to increase exchangeable Na, K, Ca, Mg, exchangeable sodium percentage, microbial biomass C and N and basal respiration in the soil. Dry matter yields of ryegrass were increased by additions of DFE other than that containing CH(3)COOH. Plant uptake of P, Ca and Mg was in the same order as their inputs in DFE but for Na; inputs were an order of magnitude greater than plant uptake. Replacement of NaOH by KOH resulted in increased accumulation of exchangeable K. The effects of added NaOH and KOH on promoting breakdown of soil aggregates during wet sieving (and formation of a < 0.25 mm size class) were similar. Replacement of H(2)PO(4) by HNO(3) is a viable but CH(3)COOH appears to have detrimental effects on plant growth. Replacement of NaOH by KOH lowers the likelihood of phytotoxic effects of Na, but K and Na have similar effects on disaggregation.

  7. Chromohalobacter is a Causing Agent for the Production of Organic Acids and Putrescine during Fermentation of Ganjang, a Korean Traditional Soy Sauce.

    PubMed

    Jung, Ji Young; Chun, Byung Hee; Jeon, Che Ok

    2015-12-01

    Ganjang, a Korean traditional fermented soy sauce, is prepared by soaking doenjang-meju (fermented soybeans) in approximately 20% (w/v) solar salt solution. The metabolites and bacterial communities during ganjang fermentation were simultaneously investigated to gain a better understanding of the roles of the microbial population. The bacterial community analysis based on denaturing gradient gel electrophoresis of 16S rRNA gene sequences showed that initially, the genus Cobetia was predominant (0 to 10 d), followed by Bacillus (5 to 74 d), and eventually, Chromohalobacter became predominant until the end of the fermentation process (74 to 374 d). Metabolite analysis using (1)H-NMR showed that carbon compounds, such as fructose, galactose, glucose, and glycerol, probably released from doenjang-meju, increased rapidly during the early fermentation period (0 to 42 d). After removal of doenjang-meju from the ganjang solution (42 d), the initial carbon compounds remained nearly constant without the increase of fermentation products. At this point, Bacillus species, which probably originated from doenjang-meju, were predominant, suggesting that Bacillus is not mainly responsible for ganjang fermentation. Fermentation products including acetate, lactate, α-aminobutyrate, γ-aminobutyrate, and putrescine increased quickly with the rapid decrease of the initial carbon compounds, while Chromohalobacter, probably derived from the solar salts, was predominant. Multivariate redundancy analysis indicated that the Chromohalobacter population was closely correlated with the production of the organic acids and putrescine during the ganjang fermentation. These results may suggest that Chromohalobacter is a causing agent responsible for the production of organic acids and putrescine during ganjang fermentation and that the solar salts, not doenjang-meju, is an important microbial source for ganjang fermentation.

  8. Rationally Developed Organic Salts of Tolfenamic Acid and Its β-Alanine Derivatives for Dual Purposes as an Anti-Inflammatory Topical Gel and Anticancer Agent.

    PubMed

    Parveen, Rumana; Sravanthi, Bommagani; Dastidar, Parthasarathi

    2017-04-04

    A new series of primary ammonium monocarboxylate (PAM) salts of a nonsteroidal anti-inflammatory drug (NSAID), namely, tolfenamic acid (TA), and its β-alanine derivatives were generated. Nearly 67 % of the salts in the series showed gelling abilities with various solvents, including water (biogenic solvent) and methyl salicylate (typically used for topical gel formulations). Gels were characterized by rheology, electron microscopy, and so forth. Structure-property correlations based on single-crystal and powder XRD data of several gelator and nongelator salts revealed intriguing insights. Studies (in vitro) on an aggressive human breast cancer cell line (MDA-MB-231) with the l-tyrosine methyl ester salt of TA (S7) revealed that the hydrogelator salt was more effective at killing cancer cells than the mother drug TA (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay); displayed better anti-inflammatory activity compared with that of TA (prostaglandin E2 assay); could be internalized within the cancer cells, as revealed by fluorescence microscopy; and inhibited effectively migration of the cancer cells. Thus, the easily accessible ambidextrous gelator salt S7 can be used for two purposes: as an anti-inflammatory topical gel and as an anticancer agent.

  9. Repositioning of 2,4-dichlorophenoxy acetic acid as a potential anti-inflammatory agent: in silico and pharmaceutical formulation study.

    PubMed

    Khedr, Mohammed A; Shehata, Tamer M; Mohamed, Maged E

    2014-12-18

    2,4-Dichlorophenoxy acetic acid (2,4-D) is a well-known plant auxin which is widely used in plant tissue culture experiments as well as a weed killer and a herbicide. In this study, 2,4-D was rediscovered as a new anti-inflammatory agent through an in silico molecular modeling and docking studies along with drug formulation and in vivo anti-inflammatory inspection. The molecular modeling and docking studies indicated high affinity of 2,4-D toward COX-2 enzyme in a way similar to Ibuprofen, suggesting a higher anti-inflammatory activity. Molecular docking by both MOE 2013.08 and Leadit 2.1.2 revealed excellent binding pattern compared to some of well-known non-steroidal anti-inflammatory drugs. 2,4-D was formulated in different gel bases. In vitro drug release experiments were used to examine the best 2,4-D formula for in vivo studies. In vivo carrageenan-induced hind paw edema inflammatory model in rats was used to test the in silico finding. 2,4-D showed potential in vivo anti-inflammatory activity and significantly reduced the concentration of prostaglandin E2 in hind paw tissues in a way similar to Ibuprofen. These results may open the door to introduce a new anti-inflammatory molecule; especially that 2,4-D is a well-investigated regarding its toxicity and side effect.

  10. Determination of alkylmethylphosphonic acids, the main metabolites of organophosphorus nerve agents, in biofluids by gas chromatography-mass spectrometry and liquid-liquid-solid-phase-transfer-catalyzed pentafluorobenzylation.

    PubMed

    Miki, A; Katagi, M; Tsuchihashi, H; Yamashita, M

    1999-01-01

    A simple gas chromatography-mass spectrometry (GC-MS) procedure has been developed for the main metabolites of organophosphorus nerve agents, alkylmethylphosphonic acids (AMPAs; alkyl = Et, i-Pr, and pinacolyl) in biofluids via extractive pentafluorobenzylation. The derivatization was carried out under liquid-liquid-solid-phase-transfer conditions using a polymer-bound tri-n-butylmethylphosphonium bromide as a catalyst. AMPAs in aqueous samples were semiquantitatively extracted into a small-volume organic layer as their pentafluorobenzyl derivatives at pH 4.5 (85 degrees C). Sample pretreatments for urine, serum, and saliva were each examined to minimize matrix interference. The detection limits of APMAs by electron-impact ionization GC-MS were around 50 ng/mL and 2.5-10 ng/mL in the full-scan and selected-ion monitoring modes, respectively. In order to detect trace-level AMPAs, negative-ion chemical ionization (NICI) was also employed to enhance sensitivity. The detection limits of AMPAs in biofluids were typically 60 pg/mL by GC-NICI-MS.

  11. Design, synthesis and biological evaluation of hybrids of β-carboline and salicylic acid as potential anticancer and apoptosis inducing agents

    PubMed Central

    Xu, Qi-Bing; Chen, Xiang-Fan; Feng, Jiao; Miao, Jie-Fei; Liu, Ji; Liu, Feng-Tao; Niu, Bi-Xi; Cai, Jin-Yang; Huang, Chao; Zhang, Yanan; Ling, Yong

    2016-01-01

    A novel series of hybrids (7a-l, 8a-l) from β-carboline and salicylic acid (SA) were designed and synthesized, and their in vitro biological activities were evaluated. Most of the hybrids displayed potent antiproliferative activity against five cancer cell lines in vitro, showing potencies superior to 5-FU and harmine. In particular, compound 8h selectively inhibited proliferation of liver cancer SMMC-7721 cells but not normal liver LO2 cells, and displayed greater inhibitory selectivity than intermediate 5h and SA. 8h also induced cancer cell apoptosis in an Annexin V-FITC/propidium iodide flow cytometry assay, and triggered the mitochondrial/caspase apoptosis by decreasing mitochondrial membrane potential which was associated with up-regulation of Bax, down-regulation of Bcl-2 and activation levels of the caspase cascade in a concentration-dependent manner. Our findings suggest that the β-carboline/SA hybrids may hold greater promise as therapeutic agents for the intervention of human cancers. PMID:27824091

  12. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... Orange Parkinson’s Awareness Month Were you exposed to herbicides during service and have Parkinson’s disease? You may ...

  13. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, M.P.; Mease, R.C.; Srivastava, S.C.

    1998-07-21

    Bicyclo[2.2.2] octane-2,3 diamine-N,N,N`,N`-tetraacetic acids (BODTA) and bicyclo[2.2.1] heptane-2,3 diamine-N,N,N`,N`-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  14. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    1998-07-21

    Bicyclo›2.2.2! octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo›2.2.1! heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  15. Rigid bifunctional chelating agents

    DOEpatents

    Sweet, Mark P.; Mease, Ronnie C.; Srivastava, Suresh C.

    2000-02-08

    Bicyclo[2.2.2]octane-2,3 diamine-N,N,N',N'-tetraacetic acids (BODTA) and bicyclo[2.2.1]heptane-2,3 diamine-N,N,N',N'-tetraacetic acid (BHDTA) are chelating agents useful in forming detectably labeled bioconjugate compounds for diagnostic and therapeutic purposes. New compounds and processes of forming BODTA and BHDTA are disclosed. Radioimmunoconjugates of the present invention show high and prolonged tumor uptake with low normal tissue uptakes.

  16. Structure, antimicrobial activity, DNA- and albumin-binding of manganese(II) complexes with the quinolone antimicrobial agents oxolinic acid and enrofloxacin.

    PubMed

    Zampakou, Marianthi; Akrivou, Melpomeni; Andreadou, Eleni G; Raptopoulou, Catherine P; Psycharis, Vassilis; Pantazaki, Anastasia A; Psomas, George

    2013-04-01

    The reaction of MnCl2 with the quinolone antibacterial drug oxolinic acid (Hoxo) results to the formation of [KMn(oxo)3(MeOH)3]. Interaction of MnCl2 with the quinolone Hoxo or enrofloxacin (Herx) and the N,N'-donor heterocyclic ligand 1,10-phenanthroline (phen) results in the formation of metal complexes with the general formula [Mn(quinolonato)2(phen)]. The crystal structures of [KMn(oxo)3(MeOH)3] and [Mn(erx)2(phen)], exhibiting a 1D polymeric and a mononuclear structure, respectively, have been determined by X-ray crystallography. In these complexes, the deprotonated bidentate quinolonato ligands are coordinated to manganese(II) ion through the pyridone oxygen and a carboxylato oxygen. All complexes can act as potential antibacterial agents with [Mn(erx)2(phen)] exhibiting the most pronounced antimicrobial activity against five different microorganisms. Interaction of the complexes with calf-thymus DNA (CT DNA), studied by UV spectroscopy, has shown that they bind to CT DNA. Competitive study with ethidium bromide (EB) has shown that all complexes can displace the DNA-bound EB indicating their binding to DNA in strong competition with EB. Intercalative binding mode is proposed for the interaction of the complexes with CT DNA and has also been verified by DNA solution viscosity measurements and cyclic voltammetry. DNA electrophoretic mobility experiments suggest that [Mn(erx)2(phen)] binds strongly to supercoiled pDNA and to linearized pDNA possibly by an intercalative manner provoking double-stranded cleavage reflecting in a nuclease-like activity. The complexes exhibit good binding propensity to human or bovine serum albumin protein showing relatively high binding constant values. The binding constants of the complexes towards CT DNA and albumins have been compared to their corresponding zinc(II) and nickel(II) complexes.

  17. Iron-[S,S']-EDDS (FeEDDS) Chelate as an Iron Source for Horticultural Crop Production: Marigold Growth and Nutrition, Spectral Properties, and Photodegradation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aminopolycarboxylic acid (APCA) complexones, commonly referred to as ligands or chelating agents, like ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) are commonly used in soluble fertilizers to supply copper (Cu), iron (Fe), manganese (Mn), and/or zinc (Zn) to p...

  18. System A Amino Acid Transport-Targeted Brain and Systemic Tumor PET Imaging Agents 2-Amino-3-[18F]Fluoro-2-Methylpropanoic Acid and 3-[18F]Fluoro-2-Methyl-2-(Methylamino)propanoic Acid

    PubMed Central

    Yu, Weiping; McConathy, Jonathan; Olson, Jeffrey J.; Goodman, Mark M.

    2014-01-01

    Introduction Amino acid based radiotracers target tumor cells through increased uptake by membrane-associated amino acid transport (AAT) systems. In the present study, four structurally related non-natural 18F-labeled amino acids, (R)- and (S)-[18F]FAMP 1 and (R)- and (S)-[18F]MeFAMP 2 have been prepared and evaluated in vitro and in vivo for their potential utility in brain and systemic tumor imaging based upon primarily system A transport with positron emission tomography (PET). Methods The transport of enantiomers of [18F]FAMP 1 and [18F]MeFAMP 2 was measured through in vitro uptake assays in human derived cancer cells including A549 (lung), DU145 (prostate), SKOV3 (ovary), MDA MB468 (breast) and U87 (brain) in the presence and absence of amino acid transporter inhibitors. The in vivo biodistribution of these tracers was evaluated using tumor mice xenografts at 15, 30, 60 and 120 min post injection. Results All four tracers showed moderate to high levels of uptake (1- 9 %ID/5×105 cells) by the cancer cell lines tested in vitro. AAT cell inhibition assays demonstrated that (R)-[18F]1 and (S)-[18F]1 entered these tumor cells via mixed AATs, likely but not limited to system A and system L. In contrast, (R)-[18F]2 and (S)-[18F]2 showed high selectivity for system A AAT. Similar to the results of in vitro cell studies, the tumor uptake of all four tracers was good to high and persisted over the 2 hours time course of in vivo studies. The accumulation of these tracers was higher in tumor than most normal tissues including blood, brain, muscle, bone, heart, and lung, and the tracers with the highest in vitro selectivity for system A AAT generally demonstrated the best tumor imaging properties. Higher uptake of these tracers was observed in the pancreas, kidney and spleen compared to tumors. Conclusions These preclinical studies demonstrate good imaging properties in a wide range of tumors for all four amino acids evaluated with (R)-[18F]2 having the highest

  19. Hydroxycarboxylic acids and salts

    DOEpatents

    Kiely, Donald E; Hash, Kirk R; Kramer-Presta, Kylie; Smith, Tyler N

    2015-02-24

    Compositions which inhibit corrosion and alter the physical properties of concrete (admixtures) are prepared from salt mixtures of hydroxycarboxylic acids, carboxylic acids, and nitric acid. The salt mixtures are prepared by neutralizing acid product mixtures from the oxidation of polyols using nitric acid and oxygen as the oxidizing agents. Nitric acid is removed from the hydroxycarboxylic acids by evaporation and diffusion dialysis.

  20. The Antimicrobial Agent Fusidic Acid Inhibits Organic Anion Transporting Polypeptide-Mediated Hepatic Clearance and May Potentiate Statin-Induced Myopathy.

    PubMed

    Eng, Heather; Scialis, Renato J; Rotter, Charles J; Lin, Jian; Lazzaro, Sarah; Varma, Manthena V; Di, Li; Feng, Bo; West, Michael; Kalgutkar, Amit S

    2016-05-01

    Chronic treatment of methicillin-resistant Staphylococcus aureus strains with the bacteriostatic agent fusidic acid (FA) is frequently associated with myopathy including rhabdomyolysis upon coadministration with statins. Because adverse effects with statins are usually the result of drug-drug interactions, we evaluated the inhibitory effects of FA against human CYP3A4 and clinically relevant drug transporters such as organic anion transporting polypeptides OATP1B1 and OATP1B3, multidrug resistant protein 1, and breast cancer resistance protein, which are involved in the oral absorption and/or systemic clearance of statins including atorvastatin, rosuvastatin, and simvastatin. FA was a weak reversible (IC50= 295 ± 1.0μM) and time-dependent (KI= 216 ± 41μM and kinact= 0.0179 ± 0.001 min(-1)) inhibitor of CYP3A4-catalyzed midazolam-1'-hydroxylase activity in human liver microsomes. FA demonstrated inhibition of multidrug resistant protein 1-mediated digoxin transport with an IC50 value of 157 ± 1.0μM and was devoid of breast cancer resistance protein inhibition (IC50> 500μM). In contrast, FA showed potent inhibition of OATP1B1- and OATP1B3-specific rosuvastatin transport with IC50 values of 1.59μM and 2.47μM, respectively. Furthermore, coadministration of oral rosuvastatin and FA to rats led to an approximately 19.3-fold and 24.6-fold increase in the rosuvastatin maximum plasma concentration and area under the plasma concentration-time curve, respectively, which could be potentially mediated through inhibitory effects of FA on rat Oatp1a4 (IC50= 2.26μM) and Oatp1b2 (IC50= 4.38μM) transporters, which are responsible for rosuvastatin uptake in rat liver. The potent inhibition of human OATP1B1/OATP1B3 by FA could attenuate hepatic uptake of statins, resulting in increased blood and tissue concentrations, potentially manifesting in musculoskeletal toxicity.

  1. Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With or Without Ribavirin in HCV-Infected Patients Taking Concomitant Acid-Reducing Agents

    PubMed Central

    Shiffman, Mitchell L; Rustgi, Vinod; Bennett, Michael; Forns, Xavier; Asselah, Tarik; Planas Vila, Ramon; Liu, Li; Pedrosa, Marcos; Moller, Jonathan; Reau, Nancy

    2016-01-01

    OBJECTIVES: Acid-reducing agents (ARAs) and proton-pump inhibitors (PPIs) that increase gastric pH can alter the bioavailability of antiviral drugs, particularly relevant in patients with advanced liver disease caused by chronic hepatitis C virus (HCV) infection seeking therapy. Using integrated data from six phase 3 studies, we report the safety and efficacy of the 3-direct-acting antiviral (DAA) regimen containing ombitasvir (OBV, an NS5A inhibitor), ritonavir-boosted paritaprevir (PTV/r, an NS3/4A protease inhibitor), and dasabuvir (DSV, an NS5B polymerase inhibitor) with or without ribavirin (RBV) for HCV genotype 1 patients taking concomitant ARAs and PPIs. METHODS: Treatment-naïve or peginterferon/RBV treatment-experienced patients with or without compensated cirrhosis received OBV/PTV/r and DSV with or without weight-based RBV. Rates of sustained virologic response (SVR), defined as HCV RNA below the lower limit of quantification, 12 weeks post-treatment (SVR12) and safety were evaluated in patients who were receiving concomitant ARAs. RESULTS: Among 2,053 patients enrolled and dosed with study drug, 410 (20%) were receiving concomitant ARAs; of these, 308 (15%) were taking concomitant PPIs. Rates of SVR12 were 95.9% (95% confidence interval (CI) 93.5–97.4%) among patients receiving an ARA, and 96.3% (95% CI 95.3–97.2%) in patients not receiving a concomitant ARA. Similarly, among patients receiving a PPI or not, SVR12 was achieved in 95.1% (95% CI 92.1–97.0%) and 96.4% (95% CI 95.5–97.2%), respectively. Response rates were high regardless of treatment regimen (with or without RBV), and among patients receiving a standard or high dose of PPIs. Regarding safety, adverse events and serious adverse events were more frequently reported in patients taking concomitant ARAs, though baseline population differences may have played a role. CONCLUSIONS: In phase 3 trials of OBV/PTV/r plus DSV and RBV in HCV genotype 1-infected patients, SVR12 rates were high

  2. Design and Engineering of a Multi-Target (Multiplex) DNA Simulant to Evaluate Nulceic Acid Based Assays for Detection of Biological Threat Agents

    DTIC Science & Technology

    2006-11-01

    Using the actual bio-threat agents for testing is impractical since producing a number of different threat bacteria and viruses, isolating and...Brucella species are recognized as potential agricultural, civilian, and military bioterrorism agents. Rickettsia are classified into two groups; the...spotted fever group (SFG), which includes R. conorii, R. sibirica, and R. rickettsii , and the typhus group (TG), which includes R. prowazekii and R

  3. Antibiotic Agents

    MedlinePlus

    ... producing ). Examples of this type are the alcohols, chlorine, peroxides, and aldehydes. The second group consists mostly ... viruses have some kind of antibacterial agent. Alcohols, chlorine and peroxides have been used for many decades ...

  4. Agent Orange

    MedlinePlus

    ... Z) Hepatitis HIV Mental Health Mental Health Home Suicide Prevention Substance Abuse Military Sexual Trauma PTSD Research ( ... eligible Veterans a free Agent Orange Registry health exam for possible long-term health problems related to ...

  5. Kinetics of enzyme inhibition by active molluscicidal agents ferulic acid, umbelliferone, eugenol and limonene in the nervous tissue of snail Lymnaea acuminata.

    PubMed

    Kumar, Pradeep; Singh, V K; Singh, D K

    2009-02-01

    Ferulic acid, umbelliferone (Ferula asafoetida), eugenol (Syzygium aromaticum) and limonene (Carum carvi) are active molluscicidal components that inhibited the activity of alkaline phosphatase and acetylcholinesterase in in vivo and in vitro exposure of Lymnaea acuminata. It was observed that ferulic acid, umbelliferone and eugenol are competitive and limonene is a competitive-non-competitive inhibitor of alkaline phosphatase. Ferulic acid and umbelliferone are competitive, whereas eugenol and limonene are competitive-non-competitive and uncompetitive inhibitors of acetylcholinesterase, respectively.

  6. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  7. Biocompatible and high-performance amino acids-capped MnWO4 nanocasting as a novel non-lanthanide contrast agent for X-ray computed tomography and T1-weighted magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Dong, Kai; Liu, Zhen; Liu, Jianhua; Huang, Sa; Li, Zhenhua; Yuan, Qinghai; Ren, Jinsong; Qu, Xiaogang

    2014-01-01

    -weighted MR imaging capabilities. As an alternative to T2-weighted MRI and CT dual-modality contrast agents, the nanoprobes can provide a positive contrast signal, which prevents confusion with the dark signals from hemorrhage and blood clots. To the best of our knowledge, this is the first report that a non-lanthanide imaging nanoprobe is applied for CT and T1-weighted MRI simultaneously. Moreover, comparing with gadolinium-based T1-weighted MRI and CT dual-modality contrast agents that were associated with nephrogenic systemic fibrosis (NSF), our contrast agents have superior biocompatibility, which is proved by a detailed study of the pharmacokinetics, biodistribution, and in vivo toxicology. Together with excellent dispersibility, high biocompatibility and superior contrast efficacy, these nanoprobes provide detailed and complementary information from dual-modality imaging over traditional single-mode imaging and bring more opportunities to the new generation of non-lanthanide nanoparticulate-based contrast agents. Electronic supplementary information (ESI) available: TEM images of MnWO4 nanoparticles synthesized at pH = 7, 180 °C pH = 9, 180 °C pH = 6, 200 °C with various amino acid molecules as capped agents, survey XPS spectra, FTIR spectrum of glycine capped MnWO4 nanorods, photos of glycine capped MnWO4 nanorods in various solutions including PBS, DMEM cell medium, and FBS, in vivo coronal view CT images of a rat before and after intravenous injection of iobitridol at different timed intervals, in vivo CT imaging of the rat one month after intravenous injection of MnWO4 nanorods, CT values of the heart, liver, spleen and kidney of a rat before and after intravenous administration of MnWO4 nanorods and iobitridol at different time intervals, hematology analysis and blood biochemical assay. See DOI: 10.1039/c3nr05455a

  8. Carbonic Anhydrase Inhibitors. Part 91. Metal Complexes of Heterocyclic Sulfonamides as Potential Pharmacological Agents in the Treatment of Gastric Acid Secretion Imbalances

    PubMed Central

    Ilies, Marc A.; Scozzafava, Andrea

    2000-01-01

    Zinc, magnesium, aluminum and copper complexes of several potent, clinically used carbonic anhydrase (CA) sulfonamide inhibitors, such as acetazolamide, methazolamide, ethoxzolamide and benzolamide were tested for their possible applications as antacids, in experimental animals. Gastric acid secretion parameters 3 days after treatment with these CA inhibitors (2 × 500 mg, twice a day), in dogs with chronic gastric fistulas, led to the observation that the gastric acid parameters BAO (the basal acid output), and MAO (the maximal acid output after stimulation with histamine) were drastically reduced, as compared to the same parameters in animals that did not receive these enzyme inhibitors. These are promising results for the possible use of metal complexes of heterocyclic sulfonamides as treatment alternatives (alone or in combination with other drugs) for gastric acid secretion imbalances. PMID:18475926

  9. [Non-steroidal anti-inflammatory agents and pregnancy. A study of renal and digestive toxicity of niflumic acid in the perinatal period].

    PubMed

    Alessandri, J L; Abossolo, T; Reynaud, I; Montbrun, A; Sommer, J C; Tilmont, P

    1994-01-01

    We report a case of intrauterine exposure to niflumic acid in a preterm neonate (35 weeks of gestation). The mother received niflumic acid (750 mg daily) during the last four days of gestation. Severe oligohydramnios was present. A transient neonatal renal failure, but also abdominal complications were observed for several days. Maternal and neonate niflumic acid levels were studied and showed an important placental transfer. Niflumic acid is a prostaglandin synthetase inhibitor. It is important that the nephrotoxicity of this vasoactive drug be known. Maternal administration of niflumic acid during the last days of gestation can induce fetal and neonatal adverse effects, especially renal failure. Prescription of all nonsteroidal anti-inflammatory drugs must be very cautious during pregnancy.

  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.

    PubMed

    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. Determination of the enantiomeric excess of chiral carboxylic acids by 31P NMR with phosphorylated derivatizing agents from C2-symmetrical diamines containing the (S)-alpha-phenylethyl group.

    PubMed

    Mastranzo, Virginia M; Quintero, Leticia; de Parrodi, Cecilia Anaya

    2007-06-01

    The use of P(III) and P(V) organophosphorus derivatizing agents prepared from C(2) symmetrical (1R,2R)- and (1S,2S)-trans-N,N'-bis-[(S)-alpha-phenylethyl]-cyclohexane-1,2-diamines 1 and 2, as well as (1R,2R)- and (1S,2S)-trans-N,N'-bis-[(S)-alpha-phenylethyl]-4-cyclohexene-1,2-diamines 3 and 4 for the determination of enantiomeric composition of chiral carboxylic acids by (31)P NMR, is described.

  12. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  13. Modes and nodes explain the mechanism of action of vortioxetine, a multimodal agent (MMA): modifying serotonin's downstream effects on glutamate and GABA (gamma amino butyric acid) release.

    PubMed

    Stahl, Stephen M

    2015-08-01

    Vortioxetine is an antidepressant with multiple pharmacologic modes of action at targets where serotonin neurons connect with other neurons. These actions modify the release of both glutamate and GABA (gamma amino butyric acid) within various brain circuits.

  14. Antineoplastic agents. 487. Synthesis and biological evaluation of the antineoplastic agent 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene and derived amino acid amides.

    PubMed

    Pettit, George R; Anderson, Collin R; Herald, Delbert L; Jung, M Katherine; Lee, Debbie J; Hamel, Ernest; Pettit, Robin K

    2003-02-13

    An efficient synthesis of 3,4-methylenedioxy-5,4'-dimethoxy-3'-amino-Z-stilbene (1c) and hydrochloride (1d) is reported. The nitrostilbene intermediate 6a was obtained via a Wittig reaction using phosphonium salt 4 and 3-nitro-4-methoxybenzaldehyde 5. A one-step reduction using zinc in acetic acid produced the synthetic objective amine 1c. The coupling of this amine with various Fmoc amino acids, followed by cleavage of the alpha-amine protecting group, resulted in a series of new cancer cell growth inhibitory amides. Amine 1c, hydrochloride 1d, glycine amide 3b, and tyrosine amide 3f had the highest level (GI50 = 10(-2)-10(-3) micro g/mL) of activity against a panel of six human and one animal (P388) cancer cell lines. Amine 1c and its hydrochloride 1d potently inhibited tubulin polymerization by binding at the colchicine site, while the amides had little activity against purified tubulin. Nevertheless, most of the amides caused a marked increase in the mitotic index of treated cells, indicating that tubulin was their intracellular target.

  15. Characterization of pH-Responsive Hydrogels of Poly(Itaconic acid-g-Ethylene Glycol) Prepared by UV-Initiated Free Radical Polymerization as Biomaterials for Oral Delivery of Bioactive Agents

    PubMed Central

    Betancourt, Tania; Pardo, Juan; Soo, Ken; Peppas, Nicholas A.

    2009-01-01

    Effective oral delivery of proteins is impeded by steep pH gradients and proteolytic enzymes in the gastrointestinal tract, as well as low absorption of the proteins into the bloodstream due to their size, charge or solubility. In the present work, pH-responsive complexation hydrogels of poly(itaconic acid) with poly(ethylene glycol) grafts were synthesized for applications in oral drug delivery. These hydrogels were expected to be in collapsed configuration at low pH due to hydrogen bonding between poly(itaconic acid) carboxyl groups and poly(ethylene glycol), and to swell with increasing pH because of charge repulsion between deprotonated carboxylic acid groups. Hydrogels were prepared by UV-initiated free radical polymerization using tetraethylene glycol as the crosslinking agent and Irgacure® 2959 as the initiator. The effect of monomer ratios, crosslinking ratio and solvent amount on the properties of the hydrogels were investigated. The composition of the hydrogels was confirmed by FTIR. Equilibrium swelling studies in the pH range of 1.2 to 7 revealed that the extent of swelling increased with increasing pH up to a pH of about 6, when no further carboxylic acid deprotonation occurred. Studies in Caco-2 colorectal carcinoma cells confirmed the cytocompatibility of these materials at concentrations of up to 5 mg/ml. PMID:19536838

  16. Interferon-inducer polyriboinosinic-polyribocytidylic acid: a potent anti-gastric ulcer agent and inhibitor of the gastric proton pump in rats.

    PubMed

    Nath, C; Rastogi, L; Dikshit, M; Patnaik, G K; Saxena, R C; Gupta, M B

    1998-01-01

    1. Polyriboinosinic-polyribocytidylic acid (Poly I:Poly C), an interferon inducer was studied for its effect on gastric ulceration in rats. Polyriboinosinic-polyribocytidylic acid (1, 2 and 4 mg/kg, i.m.) showed a dose-dependent inhibition of gastric ulcers induced by aspirin, cold restraint stress and pylorus ligation (Shay's model). Protective dose (PD50) +/- SEM values of Poly I:Poly C on these models of ulcers were 1.9 +/- 0.2, 2.3 +/- 0.4 and 2.8 +/- 0.4 (mg/kg, i.m.) respectively. 2. Polyriboinosinic-polyribocytidylic acid (10-60 micrograms) produced dose-dependent inhibition of gastric proton pump (H+/K(+)-ATPase) activity in the gastric parietal microsomal fraction. The concentration of Poly I:Poly C causing a 50% inhibition (IC50) +/- SEM was found to be 17.6 +/- 1.2 micrograms. 3. Polyriboinosinic-polyribocytidylic acid caused a significant decrease in free and total acid and pepsin and an increase in mucin content in Shay (pylorus-ligated) rat. 4. Polyriboinosinic-polyribocytidylic acid did not exert a significant influence on isolated tissue preparations for anti-cholinergic (acetylcholine-induced contraction of guinea-pig ileum) and H2-anti-histaminic (histamine-induced contraction of rat uterus and guinea-pig auricle) activities. 5. Thus, the present study indicates that Poly I:Poly C may possess anti-gastric ulcer activity as a result of inhibition of the gastric proton pump.

  17. Zinc-promoted simple synthesis of oligomer-free N(alpha)-Fmoc-amino acids using Fmoc-Cl as an acylating agent under neutral conditions.

    PubMed

    Gopi, H N; Suresh Babu, V V

    2000-04-01

    A range of N(alpha)-Fmoc-protected amino acids, including those that contain t-butyl moiety, have been synthesized by employing Fmoc-Cl utilizing the activated, commercial zinc dust-promoted synthesis of carbamates under neutral conditions. A general procedure is described that circumvents the oligomerization side reaction normally noticed in Schotten-Baumann conditions. It is a simple, convenient and clean method. Thus, Fmoc-amino acids are obtained in high yield (85-92%) and purity as checked by thin-layer chromatography, high-performance liquid chromatography and other physical methods.

  18. Amino Acid Substitutions in the Cytochrome P-450 Lanosterol 14α-Demethylase (CYP51A1) from Azole-Resistant Candida albicans Clinical Isolates Contribute to Resistance to Azole Antifungal Agents

    PubMed Central

    Sanglard, Dominique; Ischer, Françoise; Koymans, Luc; Bille, Jacques

    1998-01-01

    The cytochrome P-450 lanosterol 14α-demethylase (CYP51A1) of yeasts is involved in an important step in the biosynthesis of ergosterol. Since CYP51A1 is the target of azole antifungal agents, this enzyme is potentially prone to alterations leading to resistance to these agents. Among them, a decrease in the affinity of CYP51A1 for these agents is possible. We showed in a group of Candida albicans isolates from AIDS patients that multidrug efflux transporters were playing an important role in the resistance of C. albicans to azole antifungal agents, but without excluding the involvement of other factors (D. Sanglard, K. Kuchler, F. Ischer, J.-L. Pagani, M. Monod, and J. Bille, Antimicrob. Agents Chemother. 39:2378–2386, 1995). We therefore analyzed in closer detail changes in the affinity of CYP51A1 for azole antifungal agents. A strategy consisting of functional expression in Saccharomyces cerevisiae of the C. albicans CYP51A1 genes of sequential clinical isolates from patients was designed. This selection, which was coupled with a test of susceptibility to the azole derivatives fluconazole, ketoconazole, and itraconazole, enabled the detection of mutations in different cloned CYP51A1 genes, whose products are potentially affected in their affinity for azole derivatives. This selection enabled the detection of five different mutations in the cloned CYP51A1 genes which correlated with the occurrence of azole resistance in clinical C. albicans isolates. These mutations were as follows: replacement of the glycine at position 129 with alanine (G129A), Y132H, S405F, G464S, and R467K. While the S405F mutation was found as a single amino acid substitution in a CYP51A1 gene from an azole-resistant yeast, other mutations were found simultaneously in individual CYP51A1 genes, i.e., R467K with G464S, S405F with Y132H, G129A with G464S, and R467K with G464S and Y132H. Site-directed mutagenesis of a wild-type CYP51A1 gene was performed to estimate the effect of each of these

  19. Metal based pharmacologically active agents: Synthesis, structural characterization, molecular modeling, CT-DNA binding studies and in vitro antimicrobial screening of iron(II) bromosalicylidene amino acid chelates

    NASA Astrophysics Data System (ADS)

    Abdel-Rahman, Laila H.; El-Khatib, Rafat M.; Nassr, Lobna A. E.; Abu-Dief, Ahmed M.; Ismael, Mohamed; Seleem, Amin Abdou

    2014-01-01

    In recent years, great interest has been focused on Fe(II) Schiff base amino acid complexes as cytotoxic and antitumor drugs. Thus a series of new iron(II) complexes based on Schiff bases amino acids ligands have been designed and synthesized from condensation of 5-bromosalicylaldehyde (bs) and α-amino acids (L-alanine (ala), L-phenylalanine (phala), L-aspartic acid (aspa), L-histidine (his) and L-arginine (arg)). The structure of the investigated iron(II) complexes was elucidated using elemental analyses, infrared, ultraviolet-visible, thermogravimetric analysis, as well as conductivity and magnetic susceptibility measurements. Moreover, the stoichiometry and the stability constants of the prepared complexes have been determined spectrophotometrically. The results suggest that 5-bromosalicylaldehyde amino acid Schiff bases (bs:aa) behave as dibasic tridentate ONO ligands and coordinate to Fe(II) in octahedral geometry according to the general formula [Fe(bs:aa)2]ṡnH2O. The conductivity values between 37 and 64 ohm-1 mol-1 cm2 in ethanol imply the presence of nonelectrolyte species. The structure of the complexes was validated using quantum mechanics calculations based on accurate DFT methods. Geometry optimization of the Fe-Schiff base amino acid complexes showed that all complexes had octahedral coordination. In addition, the interaction of these complexes with (CT-DNA) was investigated at pH = 7.2, by using UV-vis absorption, viscosity and agarose gel electrophoresis measurements. Results indicated that the investigated complexes strongly bind to calf thymus DNA via intercalative mode and showed a different DNA binding according to the sequence: bsari > bshi > bsali > bsasi > bsphali. Moreover, the prepared compounds are screened for their in vitro antibacterial and antifungal activity against three types of bacteria, Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus and three types of anti fungal cultures, Penicillium purpurogenium, Aspergillus

  20. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  1. [The antiretroviral agent Fullevir].

    PubMed

    Nosik, D N; Lialina, I K; Kalnina, L B; Lobach, O A; Chataeva, M S; Rasnetsov, L D

    2009-01-01

    The antiretroviral properties of Fullevir (sodium salt of fullerenepolyhydropolyaminocaproic acid) manufactured by IntelFarm Co.) were studied in the human cell culture infected with human immunodeficiency virus (HIV). The agent was ascertained to be able to protect the cell from the cytopathic action of HIV. The 90% effective concentration (EF90) was 5 microg/ml. The 50% average toxic concentration was 400 microg/ml. Testing of different (preventive and therapeutic) Fullevir dosage regimens has shown that the drug is effective when used both an hour before and an hour after infection and when administered simultaneously with cell infection. The longer contact time for the agent with the cells increased the degree of antiviral defense. Co-administration of Fullevir and the HIV reverse transcriptase inhibitor Retrovir (azidothymidine) showed a synergistic antiretroviral effect. Thus, Fullevir may be regarded as a new promising antiretroviral drug for the treatment of HIV infection.

  2. A library synthesis of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester derivatives as anti-tumor agents.

    PubMed

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

    2004-09-06

    As a result of a hit-to-lead program using a technique of solution-phase parallel synthesis, a highly potent (2,4-dimethoxyphenyl)-[6-(3-fluorophenyl)-4-hydroxy-3-methylbenzofuran-2-yl]methanone (15b) was synthesized as an optimized derivative of 4-hydroxy-3-methyl-6-phenylbenzofuran-2-carboxylic acid ethyl ester (1), which was discovered as a screening hit from small-molecule libraries and exhibited selective cytotoxicity against a tumorigenic cell line.

  3. Effect of ph on the Electrodeposition of Cu(In, Al)Se2 from Aqueous Solution in Presence of Citric Acid as Complexing Agent

    NASA Astrophysics Data System (ADS)

    Ganjkhanlou, Yadolah; Ebadzadeh, Touradj; Kazemzad, Mahmood; Maghsoudipour, Amir; Kianpour-Rad, Mansoor

    2015-05-01

    Effect of pH on the one-step electrodeposition of Cu(In, Al)Se2 chalcopyrite layer in the presence of citric acid has been investigated by applying different electrochemical and characterization techniques. It has been observed that at pH of 1.5, nanocrystalline phase of chalcopyrite and small amount of binary phase of Cu2Se with overall composition of Cu0.91In0.32Al0.39Se2 have been deposited. On the other hand, at pH of 4, the film composition changed to Cu1.9In0.05Al0.21Se2 and an additional binary phase of copper selenide (CuSe) has also been formed. Morphological investigation illustrated that smooth and compact layer with fine spherical particles having the size of 20 nm has been obtained at pH of 1.5 whereas mixture of planar and spherical particles with size of 450-550 nm have been formed at pH of 4. In alkaline environment (pH 9), the deposition current has been noticeably decreased and no deposition occurred due to the formation of a stable complex of citric acid with metal ions. The mechanism of citric acid interaction with metal ions at different pH has also been studied by cyclic voltammetry measurement.

  4. Nucleation of calcium carbonate in presence of citric acid, DTPA, EDTA and pyromellitic acid.

    PubMed

    Westin, K-J; Rasmuson, A C

    2005-02-15

    The influence of four calcium complexing additives, i.e., citric acid (CIT), diethylenetriaminepentaacetic acid (DTPA), ethylenediaminetetraacetic acid (EDTA) and pyromellitic acid (PMA), and their concentration on the induction time of calcium carbonate nucleation has been studied. The experiments were performed by rapidly mixing a sodium carbonate solution and a calcium chloride solution of various concentrations. The induction time was obtained by recording the white light absorption of the solution. Chemical speciation was used to estimate the initial thermodynamic driving force of each experiment. The induction time was found to increase with additive concentration. The effect varies from one additive to another. CIT causes the greatest increase in induction time and PMA the least. Using classical nucleation theory the experimental data were evaluated in terms of the interfacial energy. In pure water a value of 37.8 mJ m(-2) was obtained, showing good agreement with other works. CIT, DTPA and EDTA caused a notable increase of the interfacial energy at a concentration of 0.5 mmol l(-1). PMA does not appear to have any effect at all on the interfacial energy. Different mechanisms for the influence of the additives on the measured induction time and on the estimated interfacial energy are discussed.

  5. Assessing the Impact of Backbone Length and Capping Agent on the Conformational Preferences of a Model Peptide: Conformation Specific IR and UV Spectroscopy of 2-AMINOISOBUTYRIC Acid

    NASA Astrophysics Data System (ADS)

    Gord, Joseph R.; Hewett, Daniel M.; Kubasik, Matthew A.; Zwier, Timothy S.

    2015-06-01

    2-Aminoisobutyric acid (Aib) is an achiral, α-amino acid having two equivalent methyl groups attached to C_α. Extended Aib oligomers are known to have a strong preference for the adoption of a 310-helical structure in the condensed phase. Here, we have taken a simplifying step and focused on the intrinsic folding propensities of Aib by looking at a series of capped Aib oligomers in the gas phase, free from the influence of solvent molecules and cooled in a supersonic expansion. Resonant two-photon ionization and IR-UV holeburning have been used to record single-conformation UV spectra using the Z-cap as the UV chromophore. Resonant ion-dip infrared (RIDIR) spectroscopy provides single-conformation IR spectra in the OH stretch and NH stretch regions. Data have been collected on a set of Z-(Aib)n-X oligomers with n = 1, 2, 4, 6 and X = -OH and -OMethyl. The impacts of these capping groups and differences in backbone length have been found to dramatically influence the conformational space accessed by the molecules studied here. Oligomers of n=4 have sufficient backbone length for a full turn of the 310-helix to be formed. Early interpretation of the data collected shows clear spectroscopic markers signaling the onset of 310-helix formation as well as evidence of structures incorporating C7 and C14 hydrogen bonded rings. Toniolo, C.; Bonora, G. M.; Barone, V.; Bavoso, A.; Benedetti, E.; Di Blasio, B.; Grimaldi, P.; Lelj, F.; Pavone, V.; Pedone, C., Conformation of Pleionomers of α-Aminoisobutyric Acid. Macromolecules 1985, 18, 895-902.

  6. (18)F-Fluorination of Unactivated C-H Bonds in Branched Aliphatic Amino Acids: Direct Synthesis of Oncological Positron Emission Tomography Imaging Agents.

    PubMed

    Nodwell, Matthew B; Yang, Hua; Čolović, Milena; Yuan, Zheliang; Merkens, Helen; Martin, Rainer E; Bénard, François; Schaffer, Paul; Britton, Robert

    2017-03-15

    A mild and selective photocatalytic C-H (18)F-fluorination reaction has been developed that provides direct access to (18)F-fluorinated amino acids. The biodistribution and uptake of three (18)F-labeled leucine analogues via LAT1 mediated transport in several cancer cell lines is reported. Positron emission tomography imaging of mice bearing PC3 (prostate) or U87 (glioma) xenografts using 5-[(18)F]-fluorohomoleucine showed high tumor uptake and excellent tumor visualization, highlighting the utility of this strategy for rapid tracer discovery for oncology.

  7. Supramolecular synthons in designing low molecular mass gelling agents: L-amino acid methyl ester cinnamate salts and their anti-solvent-induced instant gelation.

    PubMed

    Sahoo, Pathik; Kumar, D Krishna; Raghavan, Srinivasa R; Dastidar, Parthasarathi

    2011-04-04

    Easy access to a class of chiral gelators has been achieved by exploiting primary ammonium monocarboxylate (PAM), a supramolecular synthon. A combinatorial library comprising of 16 salts, derived from 5 L-amino acid methyl esters and 4 cinnamic acid derivatives, has been prepared and scanned for gelation. Remarkably, 14 out of 16 salts prepared (87.5 % of the salts) show moderate to good gelation abilities with various solvents, including commercial fuels, such as petrol. Anti-solvent induced instant gelation at room temperature has been achieved in all the gelator salts, indicating that the gelation process is indeed an aborted crystallization phenomenon. Rheology, optical and scanning electron microscopy, small angle neutron scattering, and X-ray powder diffraction have been used to characterize the gels. A structure-property correlation has been attempted, based on these data, in addition to the single-crystal structures of 5 gelator salts. Analysis of the FT-IR and (1)H NMR spectroscopy data reveals that some of these salts can be used as supramolecular containers for the slow release of certain pest sex pheromones. The present study clearly demonstrates the merit of crystal engineering and the supramolecular synthon approach in designing new materials with multiple properties.

  8. Probing of the combined effect of bisquaternary ammonium antimicrobial agents and acetylsalicylic acid on model phospholipid membranes: differential scanning calorimetry and mass spectrometry studies.

    PubMed

    Kasian, N A; Pashynska, V A; Vashchenko, O V; Krasnikova, A O; Gömöry, A; Kosevich, M V; Lisetski, L N

    2014-12-01

    A model molecular biosystem of hydrated dipalmitoylphosphatidylcholine (DPPC) bilayers that mimics cell biomembranes is used to probe combined membranotropic effects of drugs by instrumental techniques of molecular biophysics. Differential scanning calorimetry reveals that doping of the DPPC model membrane with individual bisquaternary ammonium compounds (BQAC) decamethoxinum, ethonium, thionium and acetylsalicylic acid (ASA) leads to lowering of the membrane melting temperature (Tm) pointing to membrane fluidization. Combined application of the basic BQAC and acidic ASA causes an opposite effect on Tm (increase), corresponding to the membrane densification. Thus, modulation of the membranotropic effects upon combined use of the drugs studied can be revealed at the level of model membranes. Formation of noncovalent supramolecular complexes of the individual BQACs and ASA with DPPC molecules, which may be involved in the mechanism of the drug-membrane interaction at the molecular level, is demonstrated by electrospray ionization (ESI) mass spectrometry. In the ternary (DPPC + ASA + BQAC) model systems, the stable complexes of the BQAC dication with the ASA anion, which may be responsible for modulation of the membranotropic effects of the drugs, were recorded by ESI mass spectrometry. The proposed approach can be further developed for preliminary evaluation of the combined effects of the drugs at the level of model lipid membranes prior to tests on living organisms.

  9. Gemini Surfactants Based on Bis-Imidazolium Alkoxy Derivatives as Effective Agents for Delivery of Nucleic Acids: A Structural and Spectroscopic Study

    PubMed Central

    Pietralik, Zuzanna; Kołodziejska, Żaneta; Weiss, Marek; Kozak, Maciej

    2015-01-01

    The success rate of gene therapy depends on the efficient transfection of genetic material into cells. The golden mean between harmlessness and high effectiveness can be provided by synthetic lipid-like molecules that are similar to the components of biological membranes. Cationic gemini surfactants are one such moiety and because of their favourable physicochemical properties (double positive electric charge, reduced toxicity, low values of critical micelle concentration), they show great potential as delivery system components for genetic material in gene therapy. The aim of this study was to investigate the process of the complexation of cationic gemini surfactants with nucleic acids: double-stranded DNA of different sizes (21 bp, ~185 bp, ~20 kbp) and siRNA (21 bp). The tested series of dicationic surfactants consists of bis-imidazolium quaternary salts with varying lengths of hydrophobic side chains (m = 5, 6, 7, 8, 9, 11, 12, 14, 16). On the basis of the data obtained by circular dichroism spectroscopy and electrophoresis, we concluded that the studied gemini surfactants with long side chains effectively bind nucleic acids at low concentrations, which leads to the formation of stable lipoplexes. Images obtained by atomic force microscopy also confirmed the formation of vesicular structures, i.e., complexes between DNA and surfactants. The cytotoxicity of selected surfactants was also tested on HeLa cells. The surfactant toxicity significantly depends on surfactant geometry (the length of hydrophobic chain). PMID:26641889

  10. Gemini Surfactants Based on Bis-Imidazolium Alkoxy Derivatives as Effective Agents for Delivery of Nucleic Acids: A Structural and Spectroscopic Study.

    PubMed

    Pietralik, Zuzanna; Kołodziejska, Żaneta; Weiss, Marek; Kozak, Maciej

    2015-01-01

    The success rate of gene therapy depends on the efficient transfection of genetic material into cells. The golden mean between harmlessness and high effectiveness can be provided by synthetic lipid-like molecules that are similar to the components of biological membranes. Cationic gemini surfactants are one such moiety and because of their favourable physicochemical properties (double positive electric charge, reduced toxicity, low values of critical micelle concentration), they show great potential as delivery system components for genetic material in gene therapy. The aim of this study was to investigate the process of the complexation of cationic gemini surfactants with nucleic acids: double-stranded DNA of different sizes (21 bp, ~185 bp, ~20 kbp) and siRNA (21 bp). The tested series of dicationic surfactants consists of bis-imidazolium quaternary salts with varying lengths of hydrophobic side chains (m = 5, 6, 7, 8, 9, 11, 12, 14, 16). On the basis of the data obtained by circular dichroism spectroscopy and electrophoresis, we concluded that the studied gemini surfactants with long side chains effectively bind nucleic acids at low concentrations, which leads to the formation of stable lipoplexes. Images obtained by atomic force microscopy also confirmed the formation of vesicular structures, i.e., complexes between DNA and surfactants. The cytotoxicity of selected surfactants was also tested on HeLa cells. The surfactant toxicity significantly depends on surfactant geometry (the length of hydrophobic chain).

  11. Vitamin-loaded electrospun cellulose acetate nanofiber mats as transdermal and dermal therapeutic agents of vitamin A acid and vitamin E.

    PubMed

    Taepaiboon, Pattama; Rungsardthong, Uracha; Supaphol, Pitt

    2007-09-01

    The present contribution reports the use of mats of electrospun cellulose acetate (CA; acetyl content=39.8%; Mw=30,000 Da) nanofibers as carriers for delivery of the model vitamins, all-trans retinoic acid or vitamin A acid (Retin-A) and alpha-tocopherol or vitamin E (Vit-E). The amounts of Vit-E and Retin-A loaded in the base CA solution [17% w/v in 2:1 v/v acetone/N,N-dimethylacetamide (DMAc)] were 5 and 0.5 wt% (based on the weight of CA), respectively. Cross-sectionally round and smooth fibers were obtained. The average diameters of these fibers ranged between 247 and 265 nm. The total immersion of the vitamin-loaded as-spun CA fiber mats in the acetate buffer solutions containing either 0.5 vol % Tween 80 or 0.5 vol % Tween 80 and 10 vol % methanol was used to arrive at the cumulative release of the vitamins from the fiber mat samples. The same was also conducted on the vitamin-loaded solution-cast CA films for comparison. In most cases, the vitamin-loaded as-spun fiber mats exhibited a gradual and monotonous increase in the cumulative release of the vitamins over the test periods (i.e., 24 h for Vit-E-loaded samples and 6 h for Retin-A-loaded ones), while the corresponding as-cast films exhibited a burst release of the vitamins.

  12. Chimeric Agents Derived from the Functionalized Amino Acid, Lacosamide, and the α-Aminoamide, Safinamide: Evaluation of Their Inhibitory Actions on Voltage-Gated Sodium Channels, and Antiseizure and Antinociception Activities and Comparison with Lacosamide and Safinamide

    PubMed Central

    2015-01-01

    The functionalized amino acid, lacosamide ((R)-2), and the α-aminoamide, safinamide ((S)-3), are neurological agents that have been extensively investigated and have displayed potent anticonvulsant activities in seizure models. Both compounds have been reported to modulate voltage-gated sodium channel activity. We have prepared a series of chimeric compounds, (R)-7–(R)-10, by merging key structural units in these two clinical agents, and then compared their activities with (R)-2 and (S)-3. Compounds were assessed for their ability to alter sodium channel kinetics for inactivation, frequency (use)-dependence, and steady-state activation and fast inactivation. We report that chimeric compounds (R)-7–(R)-10 in catecholamine A-differentiated (CAD) cells and embryonic rat cortical neurons robustly enhanced sodium channel inactivation at concentrations far lower than those required for (R)-2 and (S)-3, and that (R)-9 and (R)-10, unlike (R)-2 and (S)-3, produce sodium channel frequency (use)-dependence at low micromolar concentrations. We further show that (R)-7–(R)-10 displayed excellent anticonvulsant activities and pain-attenuating properties in the animal formalin model. Of these compounds, only (R)-7 reversed mechanical hypersensitivity in the tibial-nerve injury model for neuropathic pain in rats. PMID:25418676

  13. Regulated expression of the MRP8 and MRP14 genes in human promyelocytic leukemic HL-60 cell treated with the differentiation-inducing agents mycophenolic acid and 1{alpha},25-Dihydroxyvitamin D{sub 3}

    SciTech Connect

    Warner-Bartnicki, A.L.; Murao, S.; Collart, F.R.; Huberman, E.

    1992-12-31

    The calcium-binding proteins MRP8 and MEP14 are present in mature monomyelocytic cells and are induced during differentiation. Previous studies have demonstrated that the proteins may mediate the growth arrest in differentiating HL-60 cells. We determined the levels of a protein complex (PC) containing MRP8 and MRP14 and investigated the mechanism by which the genes encoding these proteins are regulated in HL-60 cells treated with the differentiation-inducing agent mycophenorc acid (MPA)While the PC was barely detectable in untreated cells, MPA treatment resulted in elevated levels of the PC which were maximal at 3-4 d, and were found to directly parallel gains in the steady-state levels of MRP8 and MRP14 MRNA. Transcription studies with the use of nuclear run-on experiments revealed increased transcription initiation at the MRP8 and MRP14 promoters after MPA treatment. 1{alpha},25-Dihydroxyvitamin D{sub 3}, which induces HL-60 cell differentiation by another mechanism, was also found to increase transcription initiation at the MRP8 and MRP14 promoters. Our results suggest that this initiation is the major control of maturation agent-mediated increases in MRP8 and MRPl4 gene expression, and support a role for the PC in terminal differentiation of human monomyelocytic cells.

  14. Chimeric agents derived from the functionalized amino acid, lacosamide, and the α-aminoamide, safinamide: evaluation of their inhibitory actions on voltage-gated sodium channels, and antiseizure and antinociception activities and comparison with lacosamide and safinamide.

    PubMed

    Park, Ki Duk; Yang, Xiao-Fang; Dustrude, Erik T; Wang, Yuying; Ripsch, Matthew S; White, Fletcher A; Khanna, Rajesh; Kohn, Harold

    2015-02-18

    The functionalized amino acid, lacosamide ((R)-2), and the α-aminoamide, safinamide ((S)-3), are neurological agents that have been extensively investigated and have displayed potent anticonvulsant activities in seizure models. Both compounds have been reported to modulate voltage-gated sodium channel activity. We have prepared a series of chimeric compounds, (R)-7-(R)-10, by merging key structural units in these two clinical agents, and then compared their activities with (R)-2 and (S)-3. Compounds were assessed for their ability to alter sodium channel kinetics for inactivation, frequency (use)-dependence, and steady-state activation and fast inactivation. We report that chimeric compounds (R)-7-(R)-10 in catecholamine A-differentiated (CAD) cells and embryonic rat cortical neurons robustly enhanced sodium channel inactivation at concentrations far lower than those required for (R)-2 and (S)-3, and that (R)-9 and (R)-10, unlike (R)-2 and (S)-3, produce sodium channel frequency (use)-dependence at low micromolar concentrations. We further show that (R)-7-(R)-10 displayed excellent anticonvulsant activities and pain-attenuating properties in the animal formalin model. Of these compounds, only (R)-7 reversed mechanical hypersensitivity in the tibial-nerve injury model for neuropathic pain in rats.

  15. Health care agents

    MedlinePlus

    Durable power of attorney for health care; Health care proxy; End-of-life - health care agent; Life support treatment - ... Respirator - health care agent; Ventilator - health care agent; Power of attorney - health care agent; POA - health care ...

  16. (1) H-NMR relaxometric studies of interaction between apoptosis specific MRI paramagnetic contrast agents and micellar models of apoptotic cells.

    PubMed

    Van Koninckxloo, Aurore; Henoumont, Céline; Laurent, Sophie; Muller, Robert N; Vander Elst, Luce

    2016-07-01

    (1) H-NMR was previously used to analyze the interaction between peptides (E3 and R826) selected by phage display to target apoptotic cells and phospholipidic models of these cells. In order to avoid the use of apoptotic cells and to obtain a fast evaluation of the efficiency of the potential MRI contrast agents obtained by grafting these peptides and their scramble analogs on a paramagnetic gadolinium complex, their proton relaxometric behavior was investigated in the presence of micelles mimicking healthy and apoptotic cells. Their preferential interaction with 1,2-dipalmitoyl-sn-glycero-3-phospho-l-serine micelles mimicking apoptotic cells as compared with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine micelles modeling healthy cells was shown by nuclear magnetic relaxation dispersion profiles and the enhancement of the transverse proton relaxation rates at 60 MHz. The association constant values confirm the stronger interaction of the selected conjugated peptides (Ka Gd-PMN-E3(gadolinium 2,2',2'',2'''-[((4-carboxy)pyridine-2,6-diyl)bis(methylenenitrilo)]-tetrakis acetate) grafted with E3 peptide): 2.43 10(4)  m(-1) ; Ka Gd-DTPA-R826(gadolinium ((1-p-isothiocyanatobenzyl)-diethylenetriaminepentaacetate) grafted with R826 peptide): 2.91 10(4)  m(-1) ) as compared with their conjugated scrambles (Ka Gd-PMN-E3sc(gadolinium 2,2',2'',2'''-[((4-carboxy)pyridine-2,6-diyl)bis(methylenenitrilo)]-tetrakis acetate) grafted with E3 scramble peptide): 0.18 10(4)  m(-1) ; Ka Gd-DTPA-R826sc(gadolinium ((1-p-isothiocyanatobenzyl)-diethylenetriaminepentaacetate) grafted with R826 scramble peptide): 0.32 10(4)  m(-1) ) even if the conjugation of E3 and R826 seems to decrease their interaction. Copyright © 2015 John Wiley & Sons, Ltd.

  17. ¹¹¹In-Bn-DTPA-nimotuzumab with/without modification with nuclear translocation sequence (NLS) peptides: an Auger electron-emitting radioimmunotherapeutic agent for EGFR-positive and trastuzumab (Herceptin)-resistant breast cancer.

    PubMed

    Fasih, Aisha; Fonge, Humphrey; Cai, Zhongli; Leyton, Jeffrey V; Tikhomirov, Ilia; Done, Susan J; Reilly, Raymond M

    2012-08-01

    Increased expression of epidermal growth factor receptors (EGFR) in breast cancer (BC) is often associated with trastuzumab (Herceptin)-resistant forms of the disease and represents an attractive target for novel therapies. Nimotuzumab is a humanized IgG(1) monoclonal antibody that is in clinical trials for treatment of EGFR-overexpressing malignancies. We show here that nimotuzumab derivatized with benzylisothiocyanate diethylenetriaminepentaacetic acid for labelling with the subcellular range Auger electron-emitter, (111)In and modified with nuclear translocation sequence (NLS) peptides ((111)In-NLS-Bn-DTPA-nimotuzumab) was bound, internalized and transported to the nucleus of EGFR-positive BC cells. Emission of Auger electrons in close proximity to the nucleus caused multiple DNA double-strand breaks which diminished the clonogenic survival (CS) of MDA-MB-468 cells that have high EGFR density (2.4 × 10(6) receptors/cell) to less than 3 %. (111)In-Bn-DTPA-nimotuzumab without NLS peptide modification was sevenfold less effective for killing MDA-MB-468 cells. (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification were equivalently cytotoxic to MDA-MB-231 and TrR1 BC cells that have moderate EGFR density (5.4 × 10(5) or 4.2 × 10(5) receptors/cell, respectively) reducing their CS by twofold. MDA-MB-231 cells have intrinsic trastuzumab resistance due to low HER2 density, whereas TrR1 cells have acquired resistance despite HER2 overexpression. Biodistribution and microSPECT/CT imaging revealed that (111)In-NLS-Bn-DTPA-nimotuzumab exhibited more rapid elimination from the blood and lower tumour uptake than (111)In-Bn-DTPA-nimotuzumab. Tumour uptake of the radioimmunoconjugates in mice with MDA-MB-468 xenografts was high (8-16 % injected dose/g) and was blocked by administration of an excess of unlabelled nimotuzumab, demonstrating EGFR specificity. We conclude that (111)In-Bn-DTPA-nimotuzumab with/without NLS peptide modification are promising Auger

  18. Detecting agents.

    PubMed Central

    Johnson, Susan C

    2003-01-01

    This paper reviews a recent set of behavioural studies that examine the scope and nature of the representational system underlying theory-of-mind development. Studies with typically developing infants, adults and children with autism all converge on the claim that there is a specialized input system that uses not only morphological cues, but also behavioural cues to categorize novel objects as agents. Evidence is reviewed in which 12- to 15-month-old infants treat certain non-human objects as if they have perceptual/attentional abilities, communicative abilities and goal-directed behaviour. They will follow the attentional orientation of an amorphously shaped novel object if it interacts contingently with them or with another person. They also seem to use a novel object's environmentally directed behaviour to determine its perceptual/attentional orientation and object-oriented goals. Results from adults and children with autism are strikingly similar, despite adults' contradictory beliefs about the objects in question and the failure of children with autism to ultimately develop more advanced theory-of-mind reasoning. The implications for a general theory-of-mind development are discussed. PMID:12689380

  19. Design, synthesis, in silico and in vitro studies of novel 4-methylthiazole-5-carboxylic acid derivatives as potent anti-cancer agents.

    PubMed

    Kilaru, Ravendra Babu; Valasani, Koteswara Rao; Yellapu, Nanda Kumar; Osuru, Hari Prasad; Kuruva, Chandra Sekhar; Matcha, Bhaskar; Chamarthi, Naga Raju

    2014-09-15

    Since inhibitors of mucin onco proteins are potential targets for breast cancer therapy, a series of novel 4-methylthiazole-5-carboxylic acid (1) derivatives 3a-k were synthesized by the reaction of 1 with SOCl2 followed by different bases/alcohols in the presence of triethylamine. Once synthesized and characterized, their binding modes with MUC1 were studied by molecular docking analysis using Aruglab 4.0.1 and QSAR properties were determined using HyperChem. All synthesized compounds were screened for in vitro anti-breast cancer activity against MDA-MB-231 breast adenocarcinoma cell lines by Trypan-blue cell viability assay and MTT methods. Compounds 1, 3b, 3d, 3e, 3i and 3f showed good anti-breast cancer activity. Since 1 and 3d exhibited high potent activity against MDA-MB-231 cell lines, they show could be effective mucin onco protein inhibitors.

  20. A biotin-conjugated pyridine-based isatoic anhydride, a selective room temperature RNA-acylating agent for the nucleic acid separation.

    PubMed

    Ursuegui, S; Yougnia, R; Moutin, S; Burr, A; Fossey, C; Cailly, T; Laayoun, A; Laurent, A; Fabis, F

    2015-03-28

    Isatoic anhydride derivatives, including a biotin and a disulfide linker were specifically designed for nucleic acid separation. 2'-OH selective RNA acylation, capture of biotinylated RNA adducts by streptavidin-coated magnetic beads and disulfide chemical cleavage led to isolation of highly enriched RNA samples from an initial 9/1 DNA-RNA mixture. Starting from the parent compound N-methylisatoic anhydride A which was used at 65 °C, we improved the extraction process by designing a new generation of isatoic anhydrides that are able to react under smoother conditions. Among them, a pyridine-based isatoic anhydride derivative 15f was found to be reactive at room temperature, leading to enhance the efficiency and selectivity of the extraction process by significantly reducing DNA side extraction. The extracted and purified RNAs can then be detected by RT-PCR.

  1. β-Cyclodextrin-Propyl Sulfonic Acid Catalysed One-Pot Synthesis of 1,2,4,5-Tetrasubstituted Imidazoles as Local Anesthetic Agents.

    PubMed

    Ran, Yan; Li, Ming; Zhang, Zong-Ze

    2015-11-12

    Some functionalized 1,2,4,5-tetrasubstituted imidazole derivatives were synthesized using a one-pot, four component reaction involving 1,2-diketones, aryl aldehydes, ammonium acetate and substituted aromatic amines. The synthesis has been efficiently carried out in a solvent free medium using β-cyclodextrin-propyl sulfonic acid as a catalyst to afford the target compounds in excellent yields. The local anesthetic effect of these derivatives was assessed in comparison to lidocaine as a standard using a rabbit corneal and mouse tail anesthesia model. The three most potent promising compounds were subjected to a rat sciatic nerve block assay where they showed considerable local anesthetic activity, along with minimal toxicity. Among the tested analogues, 4-(1-benzyl-4,5-diphenyl-1H-imidazol-2-yl)-N,N-dimethylaniline (5g) was identified as most potent analogue with minimal toxicity. It was further characterized by a more favourable therapeutic index than the standard.

  2. A novel class of ethacrynic acid derivatives as promising drug-like potent generation of anticancer agents with established mechanism of action.

    PubMed

    Mignani, Serge; El Brahmi, Nabil; El Kazzouli, Saïd; Eloy, Laure; Courilleau, Delphine; Caron, Joachim; Bousmina, Mosto M; Caminade, Anne-Marie; Cresteil, Thierry; Majoral, Jean-Pierre

    2016-10-21

    The well-known diuretic Ethacrynic acid (EA, Edecrin), showing low anti-proliferative activities, was chemically modified at different positions. The new EA derivatives have been tested in vitro in anti-proliferative assays on both tumor KB (epidermal carcinoma) and leukemia HL60 (promyelocytic) cells suitable targets for anticancer activity. Reduction of the α-β double bond of EA completely abolished anti-cancer activities, whereas introduction of either 2-(4-substituted phenyl)ethanamine (series A) or 4-(4-substituted phenyl)piperazine (series B) moieties generated compounds showing moderate to strong anti-proliferative activities against human cancer cell lines. Several substitutions on the phenyl of these two moieties are tolerated. The mechanism of action of the EA derivatives prepared in this study is more complex than the inhibition of glutathione S-transferase π ascribed as unique effect to EA and might help to overcome tumor resistances.

  3. Highlighting the Role of Polymer Length, Carbohydrate Size, and Nucleic Acid Type in Potency of Glycopolycation Agents for pDNA and siRNA Delivery

    PubMed Central

    Xue, Lian; Ingle, Nilesh P.; Reineke, Theresa M.

    2013-01-01

    While nucleic acids such as small interfering RNA (siRNA) and plasmid DNA (pDNA) are promising research tools and therapeutic modalities, their potential in medical applications is limited by a fundamental mechanistic understanding and inadequate efficiency. Herein, two series of carbohydrate-based polycations were synthesized and examined that varied in the degree of polymerization (n)—one containing trehalose [Tr4(n) series: Tr4(23), Tr4(55), Tr4(77)] and the other containing beta-cyclodextrin [CD4(n) series: CD4(10), CD4(26), CD4(39), CD4(143), CD4(239)]. In addition, two monosaccharide models were examined for comparison that contain tartaramidoamine (T4) and galactaramidoamine (G4 or Glycofect) repeats. Delivery profiles for pDNA were compared with those obtained for siRNA delivery and reveal that efficacy differs significantly as a function of carbohydrate type, nucleic acid type and dose, polymer length, and presence of excess polymer in the formulation. The Tr4 polymers yielded higher efficacy for pDNA delivery, yet, the CD4 polymers achieved higher siRNA delivery and gene down regulation. The T4 and Glycofect derivatives, while efficient for pDNA delivery, were completely ineffective for siRNA delivery. A strong polymer length and dose dependence on target gene knockdown was observed for all polymers tested. Also, free polymer in solution (uncomplexed) was demonstrated to be a key factor in promoting siRNA uptake and gene down regulation. PMID:24028685

  4. Design of a new, multi-purpose, light-curing adhesive comprising a silane coupling agent, acidic adhesive monomers and dithiooctanoate monomers for bonding to varied metal and dental ceramic materials.

    PubMed

    Ikemura, Kunio; Tanaka, Hisaki; Fujii, Toshihide; Deguchi, Mikito; Negoro, Noriyuki; Endo, Takeshi; Kadoma, Yoshinori

    2011-01-01

    A newly designed, light-curing adhesive was investigated for its bonding effectiveness to porcelain, alumina, zirconia, Au, Au alloy, Ag alloy, Au-Ag-Pd alloy, and Ni-Cr alloy. Four experimental adhesives were prepared using varying contents of the following: a silane coupling agent [3-methacryloyloxypropyltriethoxysilane (3-MPTES)], acidic adhesive monomers [6-methacryloyloxyhexyl phosphonoacetate(6-MHPA),6-methacryloyloxyhexyl3-phosphonopropionate(6-MHPP)and 4-methacryloyloxyethoxycarbonylphthalic acid (4-MET)], and dithiooctanoate monomers [6-methacryloyloxyhexyl 6,8-dithiooctanoate (6-MHDT) and 10-methacryloyloxydecyl 6,8-dithiooctanoate (10-MDDT)]. After all adherend surfaces were sandblasted and applied with an experimental adhesive, shear bond strengths (SBSs) of a light-curing resin composite (Beautifil II, Shofu Inc., Kyoto, Japan) to the adherend materials after 2,000 times of thermal cycling were measured. For the experimental adhesive which contained 3-MPTES (30.0 wt%), 6-MHPA (1.0 wt%), 6-MHPP (1.0 wt%), 4-MET (1.0 wt%), 6-MHDT (0.5 wt%) and 10-MDDT (0.5 wt%), it consistently yielded the highest SBS for all adherend surfaces in the range of 20.8 (4.8)-30.3 (7.9) MPa, with no significant differences among all the adherend materials (p>0.05). Therefore, the newly designed, multi-purpose, light-curing adhesive was able to deliver high SBS to all the adherend materials tested.

  5. A 3D QSAR study of betulinic acid derivatives as anti-tumor agents using topomer CoMFA: model building studies and experimental verification.

    PubMed

    Ding, Weimin; Sun, Miao; Luo, Shaman; Xu, Tao; Cao, Yibo; Yan, Xiufeng; Wang, Yang

    2013-08-22

    Betulinic acid (BA) is a natural product that exerts its cytotoxicity against various malignant carcinomas without side effects by triggering the mitochondrial pathway to apoptosis. Betulin (BE), the 28-hydroxyl analog of BA, is present in large amounts (up to 30% dry weight) in the outer bark of birch trees, and shares the same pentacyclic triterpenoid core as BA, yet exhibits no significant cytotoxicity. Topomer CoMFA studies were performed on 37 BA and BE derivatives and their in vitro anti-cancer activity results (reported as IC₅₀ values) against HT29 human colon cancer cells in the present study. All derivatives share a common pentacyclic triterpenoid core and the molecules were split into three pieces by cutting at the C-3 and C-28 sites with a consideration toward structural diversity. The analysis gave a leave-one-out cross-validation q² value of 0.722 and a non-cross-validation r² value of 0.974, which suggested that the model has good predictive ability (q² > 0.2). The contour maps illustrated that bulky and electron-donating groups would be favorable for activity at the C-28 site, and a moderately bulky and electron-withdrawing group near the C-3 site would improve this activity. BE derivatives were designed and synthesized according to the modeling result, whereby bulky electronegative groups (maleyl, phthalyl, and hexahydrophthalyl groups) were directly introduced at the C-28 position of BE. The in vitro cytotoxicity values of the given analogs against HT29 cells were consistent with the predicted values, proving that the present topomer CoMFA model is successful and that it could potentially guide the synthesis of new betulinic acid derivatives with high anti-cancer activity. The IC₅₀ values of these three new compounds were also assayed in five other tumor cell lines. 28-O-hexahydrophthalyl BE exhibited the greatest anti-cancer activities and its IC₅₀ values were lower than those of BA in all cell lines, excluding DU145 cells.

  6. Effect of kojic acid-grafted-chitosan oligosaccharides as a novel antibacterial agent on cell membrane of gram-positive and gram-negative bacteria.

    PubMed

    Liu, Xiaoli; Xia, Wenshui; Jiang, Qixing; Xu, Yanshun; Yu, Peipei

    2015-09-01

    Our work here, for the first time, reported the antibacterial activity of kojic acid-grafted-chitosan oligosaccharides (COS/KA) against three gram-positive and three gram-negative bacteria. Integrity of cell membrane, outer membrane (OM) and inner membrane (IM) permeabilization assay, alkaline phosphatase (ALP) and glucose-6-phosphate dehydrogenase (G6PDH) assay, and SDS-PAGE assay techniques were used to investigate the interactions between COS/KA and bacterial membranes. The antibacterial activity of COS/KA was higher than those of unmodified COS. The electric conductivity of bacteria suspensions increased, followed by increasing of the units of average release for ALP and G6PDH. COS/KA can also rapidly increase the 1-N-phenylanphthylamine (NPN) uptake and the release of β-galactosidase via increasing the permeability of OM and IM in Escherichia coli. SDS-PAGE indicated the content of cellular soluble proteins decreased significantly in COS/KA-treated bacteria. Hence, COS/KA has potential in food industry and biomedical sciences.

  7. Aqueous two-phase system cold-set gelation using natural and recombinant probiotic lactic acid bacteria as a gelling agent.

    PubMed

    Léonard, Lucie; Husson, Florence; Langella, Philippe; Châtel, Jean-Marc; Saurel, Rémi

    2016-05-01

    The present study aimed to entrap probiotic lactic acid bacteria (LAB) in a sodium alginate and sodium caseinate aqueous two-phase gel system. The natural acidifying properties of two therapeutic probiotic LAB were exploited to liberate calcium ions progressively from calcium carbonate (CaCO3), which caused the gelation of the co-existing phases. Bi-biopolymeric matrix gelation of GDL/CaCO3 or LAB/CaCO3 was monitored by dynamic rheological measurements, and the final gels were characterized by frequency dependence measurements and confocal laser scanning microscopy. Weak to strong gels were formed with an elastic modulus G' from 10 to 1.000Pa, respectively. After cold-set gelation of our system, confocal laser scanning microscopy showed spherical protein microdomains trapped within a calcium alginate network. LAB cells were stained to study their partition in the self-gelling matrices. Our LAB strains showed two different behaviors, which may relate to the exopolysaccharide production: (i) Lactobacillus plantarum CNRZ1997 cells were found mainly in continuous alginate networks, whereas (ii) Lactococcus lactis cells were localized in protein microdomains. This alginate-caseinate phase-separated system that was self-gelled by LAB cells may be an innovative approach for immobilizing and protecting LAB cells.

  8. Influence of acid-base conditioning on the bond strength of five luting agents employing self-etching primer to enamel and dentin.

    PubMed

    Yokomichi, Rie; Taira, Yohsuke; Soeno, Kohyoh; Atsuta, Mitsuru

    2005-06-01

    The purpose of this study was to evaluate the effect of multi-step conditioning (PA-AD conditioning) with phosphoric acid and sodium hypochlorite on the bond strength of five luting materials to enamel and dentin. Three commercial self-etching/priming systems (Panavia, Linkmax, and Multibond) and two experimental systems (ED/Super-Bond and EDFe/Super-Bond) were used. The surfaces of bovine enamel or dentin were bonded to a stainless steel rod. Tensile bond strength was determined after 24-hour immersion in water. PA-AD conditioning significantly improved the bond strength between enamel and three of the systems (Panavia, ED/Super-Bond, and EDFe/Super-Bond), but did not have any effect on Linkmax and Multibond. Likewise, PA-AD conditioning did not significantly improve the bond strength of Panavia, Linkmax, Multibond, and ED/Super-Bond to dentin. Highest bond strength to dentin (19.7 MPa) was obtained when self-etching primer containing ferric chloride (EDFe/Super-Bond) was used, but additional PA-AD conditioning significantly weakened the bonding (12.6 MPa).

  9. The Different Sensitive Behaviors of a Hydrogen-Bond Acidic Polymer-Coated SAW Sensor for Chemical Warfare Agents and Their Simulants

    PubMed Central

    Long, Yin; Wang, Yang; Du, Xiaosong; Cheng, Luhua; Wu, Penglin; Jiang, Yadong

    2015-01-01

    A linear hydrogen-bond acidic (HBA) linear functionalized polymer (PLF), was deposited onto a bare surface acoustic wave (SAW) device to fabricate a chemical sensor. Real-time responses of the sensor to a series of compounds including sarin (GB), dimethyl methylphosphonate (DMMP), mustard gas (HD), chloroethyl ethyl sulphide (2-CEES), 1,5-dichloropentane (DCP) and some organic solvents were studied. The results show that the sensor is highly sensitive to GB and DMMP, and has low sensitivity to HD and DCP, as expected. However, the sensor possesses an unexpected high sensitivity toward 2-CEES. This good sensing performance can’t be solely or mainly attributed to the dipole-dipole interaction since the sensor is not sensitive to some high polarity solvents. We believe the lone pair electrons around the sulphur atom of 2-CEES provide an electron-rich site, which facilitates the formation of hydrogen bonding between PLF and 2-CEES. On the contrary, the electron cloud on the sulphur atom of the HD molecule is offset or depleted by its two neighbouring strong electron-withdrawing groups, hence, hydrogen bonding can hardly be formed. PMID:26225975

  10. The Different Sensitive Behaviors of a Hydrogen-Bond Acidic Polymer-Coated SAW Sensor for Chemical Warfare Agents and Their Simulants.

    PubMed

    Long, Yin; Wang, Yang; Du, Xiaosong; Cheng, Luhua; Wu, Penglin; Jiang, Yadong

    2015-07-28

    A linear hydrogen-bond acidic (HBA) linear functionalized polymer (PLF), was deposited onto a bare surface acoustic wave (SAW) device to fabricate a chemical sensor. Real-time responses of the sensor to a series of compounds including sarin (GB), dimethyl methylphosphonate (DMMP), mustard gas (HD), chloroethyl ethyl sulphide (2-CEES), 1,5-dichloropentane (DCP) and some organic solvents were studied. The results show that the sensor is highly sensitive to GB and DMMP, and has low sensitivity to HD and DCP, as expected. However, the sensor possesses an unexpected high sensitivity toward 2-CEES. This good sensing performance can't be solely or mainly attributed to the dipole-dipole interaction since the sensor is not sensitive to some high polarity solvents. We believe the lone pair electrons around the sulphur atom of 2-CEES provide an electron-rich site, which facilitates the formation of hydrogen bonding between PLF and 2-CEES. On the contrary, the electron cloud on the sulphur atom of the HD molecule is offset or depleted by its two neighbouring strong electron-withdrawing groups, hence, hydrogen bonding can hardly be formed.

  11. A quantum chemical study of molecular properties and QSPR modeling of oximes, amidoximes and hydroxamic acids with nucleophilic activity against toxic organophosphorus agents

    NASA Astrophysics Data System (ADS)

    Alencar Filho, Edilson B.; Santos, Aline A.; Oliveira, Boaz G.

    2017-04-01

    The proposal of this work includes the use of quantum chemical methods and cheminformatics strategies in order to understand the structural profile and reactivity of α-nucleophiles compounds such as oximes, amidoximes and hydroxamic acids, related to hydrolysis rate of organophosphates. Theoretical conformational study of 41 compounds were carried out through the PM3 semiempirical Hamiltonian, followed by the geometry optimization at the B3LYP/6-31+G(d,p) level of theory, complemented by Polarized Continuum Model (PCM) to simulate the aqueous environment. In line with the experimental hypothesis about hydrolytic power, the strength of the Intramolecular Hydrogen Bonds (IHBs) at light of the Bader's Quantum Theory of Atoms in Molecules (QTAIM) is related to the preferential conformations of α-nucleophiles. A set of E-Dragon descriptors (1,666) were submitted to a variable selection through Ordered Predictor Selection (OPS) algorithm. Five descriptors, including atomic charges obtained from the Natural Bond Orbitals (NBO) protocol jointly with a fragment index associated to the presence/absence of IHBs, provided a Quantitative Structure-Property Relationship (QSPR) model via Multiple Linear Regression (MLR). This model showed good validation parameters (R2 = 0.80, Qloo2 = 0.67 and Qext2 = 0.81) and allowed the identification of significant physicochemical features on the molecular scaffold in order to design compounds potentially more active against organophosphorus poisoning.

  12. The case for the development of novel analgesic agents targeting both fatty acid amide hydrolase and either cyclooxygenase or TRPV1

    PubMed Central

    Fowler, CJ; Naidu, PS; Lichtman, A; Onnis, V

    2009-01-01

    Although the dominant approach to drug development is the design of compounds selective for a given target, compounds targeting more than one biological process may have superior efficacy, or alternatively a better safety profile than standard selective compounds. Here, this possibility has been explored with respect to the endocannabinoid system and pain. Compounds inhibiting the enzyme fatty acid amide hydrolase (FAAH), by increasing local endocannabinoid tone, produce potentially useful effects in models of inflammatory and possibly neuropathic pain. Local increases in levels of the endocannabinoid anandamide potentiate the actions of cyclooxygenase inhibitors, raising the possibility that compounds inhibiting both FAAH and cyclooxygenase can be as effective as non-steroidal anti-inflammatory drugs but with a reduced cyclooxygenase inhibitory ‘load’. An ibuprofen analogue active in models of visceral pain and with FAAH and cyclooxygenase inhibitory properties has been identified. Another approach, built in to the experimental analgesic compound N-arachidonoylserotonin, is the combination of FAAH inhibitory and transient receptor potential vanilloid type 1 antagonist properties. Although finding the right balance of actions upon the two targets is a key to success, it is hoped that dual-action compounds of the types illustrated in this review will prove to be useful analgesic drugs. PMID:19226258

  13. Anti-tumor effects of a novel retinoic acid metabolism blocking agent VN/14-1 in the N-methyl-N-nitrosourea-induced rat mammary carcinoma model and its effects on the uterus

    PubMed Central

    Qi, Shangle; Hu, Haiqing; Gediya, Lalji K.; Purushottamachar, Puranik; Godbole, Abhijit M.; Njar, Vincent C. O.

    2014-01-01

    VN/14-1 [4-(±)-(1H-Imidazol-1-yl)-(E)-retinoic acid], a novel retinoic acid metabolism blocking agent (RAMBA), works by inhibiting the breakdown of all-trans-retinoic acid. The purpose of this study was to evaluate the anti-tumor effects of VN/14-1 on the N-methyl-N-nitrosourea (MNU)-induced rat mammary carcinoma model, and peripheral organ effects on the uteri of immature ovariectomized (OVX) rats. In tumor burden experiments, after 56 days of administration of VN/14-1 5, 10, and 20 mg/kg/day, significant tumor reductions in mean tumor weight of 19.1, 34.4, and 44.3%, compared to tumors in control animals occurred. Cumulative tumor growth was also significantly slower in a dose-dependent manner in groups receiving 5, 10, and 20 mg/kg/day of VN/14-1 compared to growth rates in the control group. Tumor apoptosis was significant increases in animals treated with 5, 10, and 20 mg/kg/day of VN/14-1. In uterotrophic experiments, immature OVX rats given VN/14-1 significantly reduced uterine weight and blocked endometrial stimulation induced by unopposed β-estradiol (E2). In both rat models, adverse toxicities included weakness, anorexia, and reduction in body weight in the groups given the highest dose of 20 mg/kg/day. In summary, VN/14-1 inhibited tumor growth in the MNU-induced estrogen receptor (ER)-positive rat mammary tumor model, and antagonized the stimulatory effect of estrogens on the uterus. The studies suggest that VN/14-1 may be a useful novel therapy for ER-positive breast cancer. PMID:21842418

  14. Effect of complexing agent on hydrothermal growth of ZnO crystals

    NASA Astrophysics Data System (ADS)

    DiLeo, Liliane; Romano, Dana; Schaeffer, Luther; Gersten, Bonnie; Foster, Catherine; Gelabert, Maria C.

    2004-10-01

    In this study, three multidentate ligands—diethylenetriaminepentaacetate (DTPA), ethylenediaminetetraacetate (EDTA) and tetraethylenepentamine (tetren)—were investigated in the hydrothermal growth of crystals of zinc oxide (ZnO). Aqueous solutions containing zinc-ligand complexes and KOH were hydrothermally reacted and the products examined. Reactants were placed in teflon-lined stainless steel autoclaves and heated to a temperature of 200 °C, generating pressures of approximately 15 atm. Optical microscopy and scanning electron microscopy on the resulting products revealed crystals with needle and plate habits, with needle lengths up to approximately 1 mm for EDTA and plate dimensions up to 100 μm for DTPA. When only complexing agent was varied at high pH, needles were observed for all samples, with EDTA yielding the longest (300 μm) and tetren yielding the shortest (20 μm); results were analyzed by considering complex formation constants, qualitative ligand polarity and complex strain. A variable pH study with 2 aminocarboxylic ligands, EDTA and DTPA, yielded mostly needles and dendritic formations for EDTA over the studied pH range (6-14), and plates or needles for DTPA. Results of variable pH products were analyzed by considering concentrations of all zinc-ligand and zinc-hydroxy species as a function of pH.

  15. Effect of acid or alkaline catalyst and of different capping agents on the optical properties of CdS nanoparticles incorporated within a diureasil hybrid matrix

    NASA Astrophysics Data System (ADS)

    Gonçalves, Luis F. F. F.; Silva, Carlos J. R.; Kanodarwala, Fehmida K.; Stride, John A.; Pereira, Mario R.

    2015-11-01

    CdS nanoparticles (NPs) were synthesized using colloidal methods and incorporated within a diureasil hybrid matrix. The surface capping of the CdS NPs by 3-mercaptopropyltrimethoxysilane (MPTMS) and 3-aminopropyltrimethoxysilane (APTMS) organic ligands during the incorporation of the NPs within the hybrid matrix has been investigated. The matrix is based on poly(ethylene oxide)/poly(propylene oxide) chains grafted to a siliceous skeleton through urea bonds and was produced by sol-gel process. Both alkaline and acidic catalysis of the sol-gel reaction were used to evaluate the effect of each organic ligand on the optical properties of the CdS NPs. The hybrid materials were characterized by absorption, steady-state and time-resolved photoluminescence spectroscopy and High Resolution Transmission Electron Microscopy (HR-TEM). The preservation of the optical properties of the CdS NPs within the diureasil hybrids was dependent on the experimental conditions used. Both organic ligands (APTMS and MPTMS) demonstrated to be crucial in avoiding the increase of size distribution and clustering of the NPs within the hybrid matrix. The use of organic ligands was also shown to influence the level of interaction between the hybrid host and the CdS NPs. The CdS NPs showed large Stokes shifts and long average lifetimes, both in colloidal solution and in the xerogels, due to the origin of the PL emission in surface states. The CdS NPs capped with MPTMS have lower PL lifetimes compared to the other xerogel samples but still larger than the CdS NPs in the original colloidal solution. An increase in PL lifetimes of the NPs after their incorporation within the hybrid matrix is related to interaction between the NPs and the hybrid host matrix.

  16. Complexes of Silver(I) Ions and Silver Phosphate Nanoparticles with Hyaluronic Acid and/or Chitosan as Promising Antimicrobial Agents for Vascular Grafts

    PubMed Central

    Chudobova, Dagmar; Nejdl, Lukas; Gumulec, Jaromir; Krystofova, Olga; Rodrigo, Miguel Angel Merlos; Kynicky, Jindrich; Ruttkay-Nedecky, Branislav; Kopel, Pavel; Babula, Petr; Adam, Vojtech; Kizek, Rene

    2013-01-01

    Polymers are currently widely used to replace a variety of natural materials with respect to their favourable physical and chemical properties, and due to their economic advantage. One of the most important branches of application of polymers is the production of different products for medical use. In this case, it is necessary to face a significant disadvantage of polymer products due to possible and very common colonization of the surface by various microorganisms that can pose a potential danger to the patient. One of the possible solutions is to prepare polymer with antibacterial/antimicrobial properties that is resistant to bacterial colonization. The aim of this study was to contribute to the development of antimicrobial polymeric material ideal for covering vascular implants with subsequent use in transplant surgery. Therefore, the complexes of polymeric substances (hyaluronic acid and chitosan) with silver nitrate or silver phosphate nanoparticles were created, and their effects on gram-positive bacterial culture of Staphylococcus aureus were monitored. Stages of formation of complexes of silver nitrate and silver phosphate nanoparticles with polymeric compounds were characterized using electrochemical and spectrophotometric methods. Furthermore, the antimicrobial activity of complexes was determined using the methods of determination of growth curves and zones of inhibition. The results of this study revealed that the complex of chitosan, with silver phosphate nanoparticles, was the most suitable in order to have an antibacterial effect on bacterial culture of Staphylococcus aureus. Formation of this complex was under way at low concentrations of chitosan. The results of electrochemical determination corresponded with the results of spectrophotometric methods and verified good interaction and formation of the complex. The complex has an outstanding antibacterial effect and this effect was of several orders higher compared to other investigated complexes

  17. Complexes of silver(I) ions and silver phosphate nanoparticles with hyaluronic acid and/or chitosan as promising antimicrobial agents for vascular grafts.

    PubMed

    Chudobova, Dagmar; Nejdl, Lukas; Gumulec, Jaromir; Krystofova, Olga; Rodrigo, Miguel Angel Merlos; Kynicky, Jindrich; Ruttkay-Nedecky, Branislav; Kopel, Pavel; Babula, Petr; Adam, Vojtech; Kizek, Rene

    2013-06-28

    Polymers are currently widely used to replace a variety of natural materials with respect to their favourable physical and chemical properties, and due to their economic advantage. One of the most important branches of application of polymers is the production of different products for medical use. In this case, it is necessary to face a significant disadvantage of polymer products due to possible and very common colonization of the surface by various microorganisms that can pose a potential danger to the patient. One of the possible solutions is to prepare polymer with antibacterial/antimicrobial properties that is resistant to bacterial colonization. The aim of this study was to contribute to the development of antimicrobial polymeric material ideal for covering vascular implants with subsequent use in transplant surgery. Therefore, the complexes of polymeric substances (hyaluronic acid and chitosan) with silver nitrate or silver phosphate nanoparticles were created, and their effects on gram-positive bacterial culture of Staphylococcus aureus were monitored. Stages of formation of complexes of silver nitrate and silver phosphate nanoparticles with polymeric compounds were characterized using electrochemical and spectrophotometric methods. Furthermore, the antimicrobial activity of complexes was determined using the methods of determination of growth curves and zones of inhibition. The results of this study revealed that the complex of chitosan, with silver phosphate nanoparticles, was the most suitable in order to have an antibacterial effect on bacterial culture of Staphylococcus aureus. Formation of this complex was under way at low concentrations of chitosan. The results of electrochemical determination corresponded with the results of spectrophotometric methods and verified good interaction and formation of the complex. The complex has an outstanding antibacterial effect and this effect was of several orders higher compared to other investigated complexes.

  18. A Novel Polymyxin Derivative That Lacks the Fatty Acid Tail and Carries Only Three Positive Charges Has Strong Synergism with Agents Excluded by the Intact Outer Membrane▿

    PubMed Central

    Vaara, Martti; Siikanen, Osmo; Apajalahti, Juha; Fox, John; Frimodt-Møller, Niels; He, Hui; Poudyal, Anima; Li, Jian; Nation, Roger L.; Vaara, Timo

    2010-01-01

    Polymyxins are cationic lipopeptides (five cationic charges) and the last resort for the treatment of serious Gram-negative infections caused by multiresistant strains. NAB741 has a cyclic peptide portion identical to that of polymyxin B but carries in the linear peptide portion a threonyl-d-serinyl residue (no cationic charges) instead of the diaminobutyryl-threonyl-diaminobutyryl residue (two cationic charges). At the N terminus of the peptide, NAB741 carries an acetyl group instead of a mixture of methyl octanoyl and methyl heptanoyl residues. NAB741 sensitized Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii to antibiotics against which the intact outer membrane is an effective permeability barrier. When tested by using Etest strips on plates containing increasing concentrations of NAB741, the fractional inhibition concentration index (FICI) of the combination of NAB741 with rifampin ranged from ≤0.111 to 0.158 and that with clarithromycin from ≤0.094 to 0.292. When tested by the checkerboard method, the corresponding FICI values against E. coli ATCC 25922 were ≤0.141 to ≤0.155 with rifampin and 0.094 with clarithromycin. In addition, at 4 μg/ml, NAB741 decreased the MICs of azithromycin, mupirocin, fusidic acid, and vancomycin for E. coli strains and E. cloacae by factors ranging from 8 to 200. A sister peptide, NAB752, carrying a threonyl-aminobutyryl residue as the linear peptide portion, was inactive. Furthermore, NAB741 sensitized E. coli to the bactericidal activity of fresh guinea pig serum. The renal clearance of NAB741 was approximately 400-fold, 16-fold, and 8-fold higher than those measured for colistin, NAB7061, and NAB739, respectively. PMID:20479195

  19. Novel electrospun nanofibrous matrices prepared from poly(lactic acid)/poly(butylene adipate) blends for controlled release formulations of an anti-rheumatoid agent.

    PubMed

    Siafaka, Panoraia I; Barmbalexis, Panagiotis; Bikiaris, Dimitrios N

    2016-06-10

    In the present work, a series of novel formulations consisting of poly(lactic acid)/poly(butylene adipate) (PLA/PBAd) electrospun blends was examined as controlled release matrices for Leflunomide's active metabolite, Teriflunomide (TFL). The mixtures were prepared using different ratios of PLA and PBAd in order to produce nanofibrous matrices with different characteristics. Miscibility studies of the blended polymeric fibers were performed through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolytic degradation in the prepared fibers was evaluated at 37°C using a phosphate buffered saline solution. Different concentrations of (TFL) (5, 10, 15wt.%) were incorporated into nanofibers for examining the drug release behavior in simulated body fluids (SBF), at 37°C. The drug-loaded nanofibrous formulations were further characterized by Fourier Transform Infrared Spectroscopy (FTIR) spectroscopy, DSC and XRD. Gel permeation chromatography (GPC) analysis was used to evaluate the mechanism of TFL release. Artificial neural networks (ANN) and multi-linear-regression (MLR) models were used to evaluate the effect of % content of PBAd (X1) and TFL (X2) on an initial burst effect and a dissolution behavior. It was found that PLA/PBAd nanofibers have different diameters depending on the ratio of used polyesters and added drug. TFL was incorporated in an amorphous form inside the polymeric nanofibers. In vitro release studies reveal that a drug release behavior is correlated with the size of the nanofibers, drug loading and matrix degradation after a specific time. ANN dissolution modeling showed increased correlation efficacy compared to MLR.

  20. Urinary excretion of mercury after occupational exposure to mercury vapour and influence of the chelating agent meso-2,3-dimercaptosuccinic acid (DMSA).

    PubMed Central

    Roels, H A; Boeckx, M; Ceulemans, E; Lauwerys, R R

    1991-01-01

    The spontaneous and chelator mediated excretion of mercury in urine was investigated in male subjects occupationally exposed to mercury vapour (alkaline battery and chloralkali plants) who did not exhibit any sign of kidney damage. The time course of the spontaneous elimination of mercury in urine was examined in seven workers (age 22-40) who had been removed from exposure to mercury vapour (average duration of exposure 4.4 years) because their urinary mercury concentrations repeatedly exceeded 100 micrograms/g creatinine. The post exposure observation period started 10 to 29 days after the date of removal and lasted about 300 days (slow HgU elimination phase). For each worker, the kinetics of the spontaneous HgU decline followed a first order process; the biological half life ranged from 69 to 109 days (mean 90 days). The increased urinary excretion of mercury after a single oral administration of 2 g meso-2,3-dimercaptosuccinic acid (DMSA) was investigated in 16 control workers (group A; age 23 to 49), in 11 workers removed from exposure for at least two years (group B; age 27 to 41), and in 16 workers currently exposed to mercury vapour (group C; age 21 to 58). In group C, the DMSA experiment was repeated twice (three weeks before and three weeks after a holiday) after measures had been taken to reduce the mercury emission. The urinary mercury excretion was significantly higher during the 24 hours after DMSA administration in all groups compared with that in the 24 hours before. The bulk (50-70%) of the DMSA stimulated mercury excretion appeared within the first eight hours. In each group, the amount of mercury (microgram Hg/24h) excreted after DMSA was significantly correlated with that before administration of DMSA. The groups whose exposure had ceased, however, exhibited much higher correlation for coefficients (r=0.97 for group B and 0.86 for group C after three weeks of holiday) than those currently exposed to mercury vapour (r-0.66 for group C before and 9

  1. The effect and safety of polylactic acid and adipose-derived stromal vascular fraction cell as an injectable bulking agent in urologic field: a 24-week follow-up study.

    PubMed

    Lee, Seong Ho; Ko, Kyungtae; Choo, Min Soo; Lee, Won Ki; Jeong, Hyun Cheol; Cho, Sung Tae; Kim, Sung Yong; Kim, Hayoung; Kang, Won Hwa; Kim, Gun Poong; Yang, Dae Yul

    2015-02-01

    The aim of this study is to evaluate whether polylactic acid (PLA) microspheres and adipose-derived stromal vascular fraction (SVF) cells have appropriate properties as an injectable bulking agent in urologic field. Forty male Sprague-Dawley rats (2-week-old) were randomized into two groups. A total of 0.05 mL of PLA microsphere suspension and 0.05 mL of PLA microsphere suspension mixed with PKH26-labeled SVF cells were injected into bladder wall in group I and group II, respectively. At 2, 8, 16, and 24 weeks of PLA microspheres injection, the volumes of implants were measured and bladder tissues including implants were analyzed and compared grossly and histologically between groups. The distant organs were examined histologically to determine migration of PLA microspheres. At 24 weeks of implantation, 65-70% of injected volume was maintained and there was no significant difference between groups. In histological analyses, injected PLA microspheres were localized in muscular layer of bladder without infiltration into adjacent layer. From 8 to 16 weeks of injection, hybrid tissues contained collagen and actin were observed between PLA microspheres and these findings were more clear in group II. PHK26-labeled SVF cells were identified by fluorescence microscopy at all time points. There was no migration of PLA microspheres to other organs and no abnormality in weight gain and hematologic values. These results suggest the possibility of PLA microspheres as a potentially useful bulking agent in urologic field. And further investigation is needed to know synergic effect of SVF cells.

  2. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  3. Fluid extraction using carbon dioxide and organophosphorus chelating agents

    DOEpatents

    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.

  4. Fluid extraction using carbon dioxide and organophosphorus chelating agents

    DOEpatents

    Smart, N.G.; Wai, C.M.; Lin, Y.; Kwang, Y.H.

    1998-11-24

    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. 1 fig.

  5. Cleaning agents and asthma.

    PubMed

    Quirce, S; Barranco, P

    2010-01-01

    Although cleaners represent a significant part of the working population worldwide, they remain a relatively understudied occupational group. Epidemiological studies have shown an association between cleaning work and asthma, but the risk factors are uncertain. Cleaning workers are exposed to a large variety of cleaning products containing both irritants and sensitizers, as well as to common indoor allergens and pollutants. Thus, the onset or aggravation of asthma in this group could be related to an irritant-induced mechanism or to specific sensitization. The main sensitizers contained in cleaning products are disinfectants, quaternary ammonium compounds (such as benzalkonium chloride), amine compounds, and fragrances.The strongest airway irritants in cleaning products are bleach (sodium hypochlorite), hydrochloric acid, and alkaline agents (ammonia and sodium hydroxide), which are commonly mixed together. Exposure to the ingredients of cleaning products may give rise to both new-onset asthma, with or without a latency period, and work-exacerbated asthma. High-level exposure to irritants may induce reactive airways dysfunction syndrome. Cleaning workers may also have a greater relative risk of developing asthma due to prolonged low-to-moderate exposure to respiratory irritants. In addition, asthma-like symptoms without confirmed asthma are also common after exposure to cleaning agents. In many cleaners, airway symptoms induced by chemicals and odors cannot be explained by allergic or asthmatic reactions. These patients may have increased sensitivity to inhaled capsaicin, which is known to reflect sensory reactivity, and this condition is termed airway sensory hyperreactivity.

  6. Study of post-natal effect of chemopreventive agents on ethylnitrosourea-induced transplacental carcinogenesis in rats. III. Inhibitory action of indomethacin, voltaren, theophylline and epsilon-aminocaproic acid.

    PubMed

    Alexandrov, V A; Bespalov, V G; Petrov, A S; Troyan, D N; Lidaks MYu

    1996-09-01

    The influence of the arachidonic acid metabolism inhibitors, indomethacin and voltaren; an inhibitor of phosphodiesterase activity, theophylline and the protease inhibitor epsilonaminocaproic acid (EACA) on N-ethyl-N-nitrosourea (ENU)-induced transplacental carcinogenesis was studied in rats. ENU was given to pregnant rats as a single i.v. exposure at a dose of 75 mg/kg body weight on the 21st day after conception. Indomethacin and voltaren (20 p.p.m. in drinking water), theophylline (0.01% in diet) and EACA (1000 p.p.m. in drinking water) were given to the offspring throughout their post-natal life until all survivors were killed at 12 months. In the ENU-only control groups, 100% of the offspring developed tumors of brain, spinal cord, peripheral nervous system or kidneys, with a total average number of 3.1 tumors per rat. The most marked inhibitory effect was exerted by theophylline, which significantly decreased the incidence and multiplicity of total tumors, and at all main sites selectively (brain, spinal cord, peripheral nerves and kidneys). It also prolonged average survival time of the offspring. Indomethacin and voltaren significantly decreased total tumor incidence and multiplicity and brain tumor incidence and multiplicity. Indomethacin also decreased kidney tumor multiplicity and voltaren diminished spinal cord tumor multiplicity. EACA decreased multiplicities of total, brain, peripheral nerve and kidney tumors, and diminished the incidence of brain tumors. These chemopreventive agents decreased tumor incidences 20-33% and tumor multiplicities 1.4-2.7 times, compared with the ENU-only controls.

  7. 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.

    PubMed

    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 T2-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 T1 and T2 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.

  8. DISSOLUTION METHOD OF REMOVING BONDING AGENTS

    DOEpatents

    Hyman, H.H.

    1960-04-19

    A method is given for removing residual aluminumsilicon bonding agents from uranium slugs after the removal of aluminum coatings. To accomplish this the slug is immersed in an aqueous solution about 0.75 N in hydrofluoric acid and about 7 N in nitric acid.

  9. Esters of pyromellitic acid. Part II. Esters of chiral alcohols: para pyromellitate diesters as a novel class of resolving agents and use of pyromellitates as duplicands for chiral purification.

    PubMed

    Paine, John B

    2008-07-04

    Methods are presented for the preparation of pyromellitate esters of chiral terpene alcohols, including d- (3) or l-menthol (4), d-isomenthol (7), l-borneol (8), or d- (5) or l-isopinocampheol (6). Alcoholysis of PMDA in CH2Cl2/Et3N led to the formation of monoesters (e.g., 18) or diesters (11, 12), as needed, relying on the differential reactivity of the two anhydride groups. The easily isolated para diester (11) crystallized before the meta diester (12) from HOAc. Nicotine (1, 14) was efficiently resolved as 1:1 salts with the menthyl (11a, 11b) or bornyl (11f) para diesters, prototypes of what promises to be a large class of novel resolving agents. Recrystallization of para-di-d-menthyl pyromellitate (11a) greatly improved the chiral purity of the contained d-menthol (3), an example of purification by "duplication". An alternative synthesis of specific diesters took advantage of the easily separated benzyl diesters and their derived acid chlorides (19, 21), with the benzyl esters serving as temporary blocking groups removable by catalytic hydrogenolysis. Pyromellitate tetraesters (26) were prepared by base-catalyzed transesterification of the tetraethyl ester (25). Tri- l-menthyl pyromellitate (27b) was obtained by catalytic hydrogenolysis of benzyl tri-l-menthyl pyromellitate (31b), itself prepared from the alcoholysis of benzyl pyromellitate triacid chloride (30) with l-menthol (4).

  10. Qualitative detection of diuretics and acidic metabolites of other doping agents in human urine by high-performance liquid chromatography-tandem mass spectrometry: comparison between liquid-liquid extraction and direct injection.

    PubMed

    Deventer, K; Pozo, O J; Van Eenoo, P; Delbeke, F T

    2009-07-31

    Direct injection of urine has gained interest in the field of analytical toxicology, including doping control analysis. However, implementation of a direct urinalysis method for the LC-MS/MS detection of 34 diuretics and 9 other doping agents yielded several analytical problems, which were not observed using a traditional liquid-liquid extraction. Therefore a comparative study was made between liquid-liquid extraction and direct injection. Comparison of validation results showed that the liquid-liquid extraction at pH 7 allows to analyze samples without major drawbacks regarding matrix effects. Hence, good sensitivity was observed and detection limits ranged between 1 and 250 ng/mL for all compounds. In the direct injection approach shifted retention times were observed for several acidic and basic compounds due to unwanted matrix effects. This shift was reduced by a 25-fold dilution of the urine samples. Besides the improved retention time stability the diluted samples also exhibited lower ion suppression than the undiluted ones. After 25-fold dilution, detection limits ranged between 10 and 250 ng/mL for all compounds. Since these detection limits are at or below the minimum required performance level, imposed by the World Anti-Doping Agency, the method could be applied to routine anti-doping analysis. Samples, previously declared positive, were reanalysed using both the liquid-liquid extraction and direct injection. With both techniques all 26 samples were found to be positive, showing the applicability of direct injection for the analysis of diuretics.

  11. Fluoroquinolone antimicrobial agents.

    PubMed Central

    Wolfson, J S; Hooper, D C

    1989-01-01

    The fluoroquinolones, a new class of potent orally absorbed antimicrobial agents, are reviewed, considering structure, mechanisms of action and resistance, spectrum, variables affecting activity in vitro, pharmacokinetic properties, clinical efficacy, emergence of resistance, and tolerability. The primary bacterial target is the enzyme deoxyribonucleic acid gyrase. Bacterial resistance occurs by chromosomal mutations altering deoxyribonucleic acid gyrase and decreasing drug permeation. The drugs are bactericidal and potent in vitro against members of the family Enterobacteriaceae, Haemophilus spp., and Neisseria spp., have good activity against Pseudomonas aeruginosa and staphylococci, and (with several exceptions) are less potent against streptococci and have fair to poor activity against anaerobic species. Potency in vitro decreases in the presence of low pH, magnesium ions, or urine but is little affected by different media, increased inoculum, or serum. The effects of the drugs in combination with a beta-lactam or aminoglycoside are often additive, occasionally synergistic, and rarely antagonistic. The agents are orally absorbed, require at most twice-daily dosing, and achieve high concentrations in urine, feces, and kidney and good concentrations in lung, bone, prostate, and other tissues. The drugs are efficacious in treatment of a variety of bacterial infections, including uncomplicated and complicated urinary tract infections, bacterial gastroenteritis, and gonorrhea, and show promise for therapy of prostatitis, respiratory tract infections, osteomyelitis, and cutaneous infections, particularly when caused by aerobic gram-negative bacilli. Fluoroquinolones have also proved to be efficacious for prophylaxis against travelers' diarrhea and infection with gram-negative bacilli in neutropenic patients. The drugs are effective in eliminating carriage of Neisseria meningitidis. Patient tolerability appears acceptable, with gastrointestinal or central nervous

  12. The effects of para-chloromercuribenzoic acid and different oxidative and sulfhydryl agents on a novel, non-AT1, non-AT2 angiotensin binding site identified as neurolysin

    PubMed Central

    Santos, Kira L.; Vento, Megan A; Wright, John W.; Speth, Robert C.

    2013-01-01

    A novel, non-AT1, non-AT2 brain binding site for angiotensin peptides that is unmasked by p-chloromercuribenzoate (PCMB) has been identified as a membrane associated variant of neurolysin. The ability of different organic and inorganic oxidative and sulfhydryl reactive agents to unmask or inhibit 125I-Sar1Ile8 angiotensin II (SI-Ang II) binding to this site was presently examined. In tissue membranes from homogenates of rat brain and testis incubated in assay buffer containing losartan (10 μM) and PD123319 (10 μM) plus 100 μM PCMB, 5 of the 39 compounds tested inhibited 125I-SI Ang II binding in brain and testis. Mersalyl acid, mercuric chloride (HgCl2) and silver nitrate (AgNO3) most potently inhibited 125I-SI Ang II binding with IC50’s ~1–20 μM This HgCl2 inhibition was independent of any interaction of HgCl2 with angiotensin II (Ang II) based on the lack of effect of HgCl2 on the dipsogenic effects of intracerebroventricularly administered Ang II and 125I-SI Ang II binding to AT1 receptors in the liver. Among sulfhydryl reagents, cysteamine and reduced glutathione (GSH), but not oxidized glutathione (GSSG) up to 1 mM, inhibited PCMB-unmasked 125I-SI Ang II binding in brain and testis. Thimerosal and 4-hydroxymercuribenzoate moderately inhibited PCMB-unmasked 125I-SI Ang II binding in brain and testis at 100 μM; however, they also unmasked non-AT1, non-AT2 binding independent of PCMB. 4-hydroxybenzoic acid did not promote 125 I-SI Ang II binding to this binding site indicating that only specific organomercurial compounds can unmask the binding site. The common denominator for all of these interacting substances is the ability to bind to protein cysteine sulfur. Comparison of cysteines between neurolysin and the closely related enzyme thimet oligopeptidase revealed an unconserved cysteine (cys650, based on the full length variant) in the proposed ligand binding channel (Brown et al., 2001) [1] near the active site of neurolysin. It is proposed that the

  13. The effects of para-chloromercuribenzoic acid and different oxidative and sulfhydryl agents on a novel, non-AT1, non-AT2 angiotensin binding site identified as neurolysin.

    PubMed

    Santos, Kira L; Vento, Megan A; Wright, John W; Speth, Robert C

    2013-06-10

    A novel, non-AT1, non-AT2 brain binding site for angiotensin peptides that is unmasked by p-chloromercuribenzoate (PCMB) has been identified as a membrane associated variant of neurolysin. The ability of different organic and inorganic oxidative and sulfhydryl reactive agents to unmask or inhibit 125I-Sar1Ile8 angiotensin II (SI-Ang II) binding to this site was presently examined. In tissue membranes from homogenates of rat brain and testis incubated in assay buffer containing losartan (10 μM) and PD123319 (10 μM) plus 100 μM PCMB, 5 of the 39 compounds tested inhibited 125I-SI Ang II binding in brain and testis. Mersalyl acid, mercuric chloride (HgCl2) and silver nitrate (AgNO3) most potently inhibited 125I-SI Ang II binding with IC50s ~1-20 μM. This HgCl2 inhibition was independent of any interaction of HgCl2 with angiotensin II (Ang II) based on the lack of effect of HgCl2 on the dipsogenic effects of intracerebroventricularly administered Ang II and 125I-SI Ang II binding to AT1 receptors in the liver. Among sulfhydryl reagents, cysteamine and reduced glutathione (GSH), but not oxidized glutathione (GSSG) up to 1mM, inhibited PCMB-unmasked 125I-SI Ang II binding in brain and testis. Thimerosal and 4-hydroxymercuribenzoate moderately inhibited PCMB-unmasked 125I-SI Ang II binding in brain and testis at 100 μM; however, they also unmasked non-AT1, non-AT2 binding independent of PCMB. 4-Hydroxybenzoic acid did not promote 125 I-SI Ang II binding to this binding site indicating that only specific organomercurial compounds can unmask the binding site. The common denominator for all of these interacting substances is the ability to bind to protein cysteine sulfur. Comparison of cysteines between neurolysin and the closely related enzyme thimet oligopeptidase revealed an unconserved cysteine (cys650, based on the full length variant) in the proposed ligand binding channel (Brown et al., 2001) [45] near the active site of neurolysin. It is proposed that the

  14. Stable, Electroinactive Wetting Agent For Fuel Cells

    NASA Technical Reports Server (NTRS)

    Prakash, Surya G.; Olah, George A.; Narayanan, Sekharipuram R.; Surampudi, Subbarao; Halpert, Gerald

    1994-01-01

    Straight-chain perfluorooctanesulfonic acid (C8 acid) identified as innocuous and stable wetting agent for use with polytetrafluoroethylene-containing electrodes in liquid-feed direct-oxidation fuel cells suggested for use in vehicles and portable power supplies. C8 acid in small concentrations in aqueous liquid solutions of methanol, trimethoxymethane, dimethoxymethane, and trioxane enables oxidation of these substances by use of commercially available electrodes of type designed originally for use with gases. This function specific to C8 acid molecule and not achieved by other related perfluorolkanesulfonic acids.

  15. Biological warfare agents.

    PubMed

    Pohanka, Miroslav; Kuca, Kamil

    2010-01-01

    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  16. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  17. Chemical warfare agents.

    PubMed

    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 efficacy and safety of intra-articular injection of hyaluronic acid in the knee and physical therapy agents to treat Kashin-Beck disease: A prospective interventional study

    PubMed Central

    Yang, Pinglin; Guo, Xiong; He, Xijing; Zang, Quanjin; Wang, Guoyu; Xu, Peng; Wang, Weizhuo

    2016-01-01

    The aim of the present study was to determine whether hyaluronic acid (HA) or physical therapy agents (PTA) can improve functional parameters in patients with knee Kashin-Beck disease (KBD). For 2 years, patients (n=55) were treated with HA weekly for 5 weeks, then received 6th and 7th injections on the 3rd and 6th month, respectively, for 7 injections in total. Patients (n=53) were treated with PTA five times a week for 3 weeks every month for 6 months. The patients were evaluated with the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and the visual analog pain scale (VAS). Trial registration, ChiCTR-TRC-12002189 (http://www.chictr.org/). During the study, following treatment interruption, pain increased in the PTA group (from a mean value of 85.7±83.8 mm at month 12 to 145.2±128.8 mm at month 18 and 201.3±150.5 mm at month 24), while it remained stable in the HA group (from a mean value of 80.7±70.6 mm at month 12 to 90.1±95.2 mm at month 18 and 82.6±85.3 mm at month 24), with a statistically significant difference in favor of HA at month 18 (P<0.05) and month 24 (P<0.05). Joint stiffness, physical function and total WOMAC showed the same trend as pain. The global efficacy judgments by the patients and the investigators showed a statistically significant difference in favor of HA at month 18 (P<0.05) and month 24 (P<0.05). In conclusion, although all the patients improved in terms of pain and function, HA was superior to PTA alone for pain relief and lasting effect. PMID:27446269

  19. 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

    PubMed Central

    Daryaei, Iman; Pagel, Mark D

    2016-01-01

    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 T2-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 T1 and T2 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. PMID:27747191

  20. In Vivo Cholinesterase Inhibitory Specificity of Organophosphorus Nerve Agents

    DTIC Science & Technology

    2005-10-26

    of the hydrolysis products of V-agents are presumably phoric acid anhydrides , and their structures are very simi- toxic. Also, V-agents may be...slowly with carboxylesterases and phospho- anhydrides . GF contains a cyclohexyl substituent. rylphosphatases than do G-agents [3]. The G-type nerve agents...USA). Tris(hydroxymethyl) 2.4. AChE analysis amino methane was purchased from Fischer Scientific (Fair Lawn, NJ, USA). The bicinchronic (BCA) protein

  1. Delta agent (Hepatitis D)

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/000216.htm Delta agent (Hepatitis D) To use the sharing features on this page, please enable JavaScript. Delta agent is a type of virus called hepatitis ...

  2. Animal Capture Agents

    DTIC Science & Technology

    1990-01-01

    agents and delivery systems reviewed . Questionnaires were sent to 137 Air Force bases to obtain information about the chemical agents and delivery systems...used by animal control personnel. A literature review included chemical agents, delivery methods, toxicity information and emergency procedures from...34-like agent. Users should familiarize themselves with catatonia in general and particularly that its successful use as an immobilizer doesn’t necessarily

  3. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  4. Intelligent Agents: A Primer.

    ERIC Educational Resources Information Center

    Yu, Edmund; Feldman, Susan

    1999-01-01

    Provides an in-depth introduction to the various technologies that are bringing intelligent agents into the forefront of information technology, explaining how such agents work, the standards involved, and how agent-based applications can be developed. (Author/AEF)

  5. Phytonutrients as therapeutic agents.

    PubMed

    Gupta, Charu; Prakash, Dhan

    2014-09-01

    Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ω-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization.

  6. Standard Agent Framework 1

    SciTech Connect

    Goldsmith, Steven Y.

    1999-04-06

    The Standard Agent framework provides an extensible object-oriented development environment suitable for use in both research and applications projects. The SAF provides a means for constructing and customizing multi-agent systems through specialization of standard base classes (architecture-driven framework) and by composition of component classes (data driven framework). The standard agent system is implemented as an extensible object-centerd framework. Four concrete base classes are developed: (1) Standard Agency; (2) Standard Agent; (3) Human Factor, and (4) Resources. The object-centered framework developed and utilized provides the best comprimise between generality and flexibility available in agent development systems today.

  7. Bifunctional alkylating agent-induced p53 and nonclassical nuclear factor kappaB responses and cell death are altered by caffeic acid phenethyl ester: a potential role for antioxidant/electrophilic response-element signaling.

    PubMed

    Minsavage, Gary D; Dillman, James F

    2007-04-01

    Bifunctional alkylating agents (BFA) such as mechlorethamine (nitrogen mustard) and bis-(2-chloroethyl) sulfide (sulfur mustard; SM) covalently modify DNA and protein. The roles of nuclear factor kappaB (NF-kappaB) and p53, transcription factors involved in inflammatory and cell death signaling, were examined in normal human epidermal keratinocytes (NHEK) and immortalized HaCaT keratinocytes, a p53-mutated cell line, to delineate molecular mechanisms of action of BFA. NHEK and HaCaT cells exhibited classical NF-kappaB signaling as degradation of inhibitor protein of NF-kappaBalpha (IkappaBalpha) occurred within 5 min after exposure to tumor necrosis factor-alpha. However, exposure to BFA induced nonclassical NF-kappaB signaling as loss of IkappaBalpha was not observed until 2 or 6 h in NHEK or HaCaT cells, respectively. Exposure of an NF-kappaB reporter gene-expressing HaCaT cell line to 12.5, 50, or 100 muM SM activated the reporter gene within 9 h. Pretreatment with caffeic acid phenethyl ester (CAPE), a known inhibitor of NF-kappaB signaling, significantly decreased BFA-induced reporter gene activity. A 1.5-h pretreatment or 30-min postexposure treatment with CAPE prevented BFA-induced loss of membrane integrity by 24 h in HaCaT cells but not in NHEK. CAPE disrupted BFA-induced phosphorylation of p53 and p90 ribosomal S6 kinase (p90RSK) in both cell lines. CAPE also increased nuclear factor E2-related factor 2 and decreased aryl hydrocarbon receptor protein expression, both of which are involved in antioxidant/electrophilic response element (ARE/EpRE) signaling. Thus, disruption of p53/p90RSK-mediated NF-kappaB signaling and activation of ARE/EpRE pathways may be effective strategies to delineate mechanisms of action of BFA-induced inflammation and cell death signaling in immortalized versus normal skin systems.

  8. Synthesis of 5-alkylated barbituric acids and 3-alkylated indoles via microwave-assisted three-component reactions in solvent-free conditions using Hantzsch 1,4-dihydropyridines as reducing agents.

    PubMed

    Baruah, Biswajita; Seetham Naidu, P; Borah, Pallabi; Bhuyan, Pulak J

    2012-05-01

    Reaction of barbituric acids with aldehydes and dihydropyridines in one pot under microwave (MW) irradiation in the absence of solvent, affords 55–82% of the 5-benzylated barbituric acids. Use of alkyl nitriles or barbituric acids with indole-3-aldehyde and dihydropyridine (DHP) afforded 3-alkylated indoles in 57–76 % yield. In each case DHPs are converted to pyridines.

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

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... amino acid sequence at the fusion (F) protein cleavage site that is consistent with virulent strains of... not confirm the absence of a virulent virus. (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent...

  10. 9 CFR 121.3 - VS select agents and toxins.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... amino acid sequence at the fusion (F) protein cleavage site that is consistent with virulent strains of... not confirm the absence of a virulent virus. (c) Genetic elements, recombinant nucleic acids, and recombinant organisms: (1) Nucleic acids that can produce infectious forms of any of the select agent...

  11. Moral actor, selfish agent.

    PubMed

    Frimer, Jeremy A; Schaefer, Nicola K; Oakes, Harrison

    2014-05-01

    People are motivated to behave selfishly while appearing moral. This tension gives rise to 2 divergently motivated selves. The actor-the watched self-tends to be moral; the agent-the self as executor-tends to be selfish. Three studies present direct evidence of the actor's and agent's distinct motives. To recruit the self-as-actor, we asked people to rate the importance of various goals. To recruit the self-as-agent, we asked people to describe their goals verbally. In Study 1, actors claimed their goals were equally about helping the self and others (viz., moral); agents claimed their goals were primarily about helping the self (viz., selfish). This disparity was evident in both individualist and collectivist cultures, attesting to the universality of the selfish agent. Study 2 compared actors' and agents' motives to those of people role-playing highly prosocial or selfish exemplars. In content (Study 2a) and in the impressions they made on an outside observer (Study 2b), actors' motives were similar to those of the prosocial role-players, whereas agents' motives were similar to those of the selfish role-players. Study 3 accounted for the difference between the actor and agent: Participants claimed that their agent's motives were the more realistic and that their actor's motives were the more idealistic. The selfish agent/moral actor duality may account for why implicit and explicit measures of the same construct diverge, and why feeling watched brings out the better angels of human nature.

  12. Agent Architectures for Compliance

    NASA Astrophysics Data System (ADS)

    Burgemeestre, Brigitte; Hulstijn, Joris; Tan, Yao-Hua

    A Normative Multi-Agent System consists of autonomous agents who must comply with social norms. Different kinds of norms make different assumptions about the cognitive architecture of the agents. For example, a principle-based norm assumes that agents can reflect upon the consequences of their actions; a rule-based formulation only assumes that agents can avoid violations. In this paper we present several cognitive agent architectures for self-monitoring and compliance. We show how different assumptions about the cognitive architecture lead to different information needs when assessing compliance. The approach is validated with a case study of horizontal monitoring, an approach to corporate tax auditing recently introduced by the Dutch Customs and Tax Authority.

  13. Salicylic Acid Topical

    MedlinePlus

    Propa pH® Peel-Off Acne Mask ... pimples and skin blemishes in people who have acne. Topical salicylic acid is also used to treat ... medications called keratolytic agents. Topical salicylic acid treats acne by reducing swelling and redness and unplugging blocked ...

  14. Comparative Evaluation of Firefighting Foam Agents

    DTIC Science & Technology

    1979-08-01

    active agents chemists to develop new and improved in combination with foam stabilizers products which would materially and pour point depressants or...Active Materials with conventional hydrocarbon from Perfluorocarboxylic and Per- surfactants. These fundamental fluorosulfonic Acids" appeared in...end is hydrophilic, or water loving, interfacial equilibrium condition. and the other is hydrophobic and/or oleophobic ; that is, water and oil

  15. 21 CFR 181.28 - Release agents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Release agents. 181.28 Section 181.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) PRIOR-SANCTIONED....97 at 25 °C, refractive index 1.400 to 1.404 at 25 °C). Linoleamide (linoleic acid amide)....

  16. Change Agent Survival Guide

    ERIC Educational Resources Information Center

    Dunbar, Folwell L.

    2011-01-01

    Consulting is a rough racket. Only a tarantula hair above IRS agents, meter maids and used car sales people, the profession is a prickly burr for slings and arrows. Throw in education, focus on dysfunctional schools and call oneself a "change agent," and this bad rap all but disappears. Unfortunately, though, consulting/coaching/mentoring in…

  17. Detecting biological warfare agents.

    PubMed

    Song, Linan; Ahn, Soohyoun; Walt, David R

    2005-10-01

    We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array.

  18. Travel Agent Course Outline.

    ERIC Educational Resources Information Center

    British Columbia Dept. of Education, Victoria.

    Written for college entry-level travel agent training courses, this course outline can also be used for inservice training programs offered by travel agencies. The outline provides information on the work of a travel agent and gives clear statements on what learners must be able to do by the end of their training. Material is divided into eight…

  19. Detecting Biological Warfare Agents

    PubMed Central

    Song, Linan; Ahn, Soohyoun

    2005-01-01

    We developed a fiber-optic, microsphere-based, high-density array composed of 18 species-specific probe microsensors to identify biological warfare agents. We simultaneously identified multiple biological warfare agents in environmental samples by looking at specific probe responses after hybridization and response patterns of the multiplexed array. PMID:16318712

  20. How do agents represent?

    NASA Astrophysics Data System (ADS)

    Ryan, Alex

    Representation is inherent to the concept of an agent, but its importance in complex systems has not yet been widely recognised. In this paper I introduce Peirce's theory of signs, which facilitates a definition of representation in general. In summary, representation means that for some agent, a model is used to stand in for another entity in a way that shapes the behaviour of the agent with respect to that entity. Representation in general is then related to the theories of representation that have developed within different disciplines. I compare theories of representation from metaphysics, military theory and systems theory. Additional complications arise in explaining the special case of mental representations, which is the focus of cognitive science. I consider the dominant theory of cognition — that the brain is a representational device — as well as the sceptical anti-representational response. Finally, I argue that representation distinguishes agents from non-representational objects: agents are objects capable of representation.

  1. 7 CFR 331.3 - PPQ select agents and toxins.

    Code of Federal Regulations, 2010 CFR

    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:...

  2. 42 CFR 73.3 - HHS select agents and toxins.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  3. 42 CFR 73.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... have been genetically modified. (d) Overlap select agents or toxins that meet any of the following... Elements, Recombinant and/or Synthetic Nucleic Acids, and Recombinant and/or Synthetic Organisms:...

  4. 42 CFR 73.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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:...

  5. 7 CFR 331.3 - PPQ select agents and toxins.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) 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:...

  6. 7 CFR 331.3 - PPQ select agents and toxins.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (b) of this section that have been genetically modified. (d) Select agents or toxins that meet any of..., and recombinant and/or synthetic organisms: (1) Nucleic acids that can produce infectious forms of...

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (b) of this section that have been genetically modified. (d) Select agents or toxins that meet any of..., and recombinant and/or synthetic organisms: (1) Nucleic acids that can produce infectious forms of...

  8. 42 CFR 73.3 - HHS select agents and toxins.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  9. 21 CFR 176.200 - Defoaming agents used in coatings.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... defoaming agents containing dimethylpolysiloxane. Polyethylene Polyethylene, oxidized Polyethylene glycol (200) dilaurate Polyethylene glycol (400) dioleate Polyethylene glycol (600) dioleate Polyethylene glycol (400) esters of coconut oil fatty acids Polyethylene glycol (400) monooleate Polyethylene...

  10. 21 CFR 176.200 - Defoaming agents used in coatings.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... defoaming agents containing dimethylpolysiloxane. Polyethylene Polyethylene, oxidized Polyethylene glycol (200) dilaurate Polyethylene glycol (400) dioleate Polyethylene glycol (600) dioleate Polyethylene glycol (400) esters of coconut oil fatty acids Polyethylene glycol (400) monooleate Polyethylene...

  11. 21 CFR 176.200 - Defoaming agents used in coatings.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... defoaming agents containing dimethylpolysiloxane. Polyethylene Polyethylene, oxidized Polyethylene glycol (200) dilaurate Polyethylene glycol (400) dioleate Polyethylene glycol (600) dioleate Polyethylene glycol (400) esters of coconut oil fatty acids Polyethylene glycol (400) monooleate Polyethylene...

  12. 21 CFR 176.200 - Defoaming agents used in coatings.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... defoaming agents containing dimethylpolysiloxane. Polyethylene Polyethylene, oxidized Polyethylene glycol (200) dilaurate Polyethylene glycol (400) dioleate Polyethylene glycol (600) dioleate Polyethylene glycol (400) esters of coconut oil fatty acids Polyethylene glycol (400) monooleate Polyethylene...

  13. 42 CFR 73.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... have been genetically modified. (d) Overlap select agents or toxins that meet any of the following... Elements, Recombinant and/or Synthetic Nucleic Acids, and Recombinant and/or Synthetic Organisms: (1... within the exclusion category. (e) An attenuated strain of a select agent, or a select toxin modified...

  14. Biological warfare agents.

    PubMed

    Thavaselvam, Duraipandian; Vijayaraghavan, Rajagopalan

    2010-07-01

    The recent bioterrorist attacks using anthrax spores have emphasized the need to detect and decontaminate critical facilities in the shortest possible time. There has been a remarkable progress in the detection, protection and decontamination of biological warfare agents as many instrumentation platforms and detection methodologies are developed and commissioned. Even then the threat of biological warfare agents and their use in bioterrorist attacks still remain a leading cause of global concern. Furthermore in the past decade there have been threats due to the emerging new diseases and also the re-emergence of old diseases and development of antimicrobial resistance and spread to new geographical regions. The preparedness against these agents need complete knowledge about the disease, better research and training facilities, diagnostic facilities and improved public health system. This review on the biological warfare agents will provide information on the biological warfare agents, their mode of transmission and spread and also the detection systems available to detect them. In addition the current information on the availability of commercially available and developing technologies against biological warfare agents has also been discussed. The risk that arise due to the use of these agents in warfare or bioterrorism related scenario can be mitigated with the availability of improved detection technologies.

  15. Topical hemostatic agents: a review.

    PubMed

    Palm, Melanie D; Altman, Jeffrey S

    2008-04-01

    Topical hemostatic agents play an important role in both common and specialized dermatologic procedures. These agents can be classified based on their mechanism of action and include physical or mechanical agents, caustic agents, biologic physical agents, and physiologic agents. Some agents induce protein coagulation and precipitation resulting in occlusion of small cutaneous vessels, while others take advantage of latter stages in the coagulation cascade, activating biologic responses to bleeding. Traditional and newer topical hemostatic agents are discussed in this review, and the benefits and costs of each agent will be provided.

  16. Development of polyimide foams with blowing agents

    NASA Technical Reports Server (NTRS)

    Gagliani, John (Inventor); Sorathia, Usman A. K. (Inventor); Lee, Raymond (Inventor)

    1985-01-01

    A method of preparing a polyimide foam which includes the steps of: preparing, foaming, and curing a precursor containing at least one alkyl ester of 3,3'4,4'-benzophenonetetracarboxylic acid; a meta- or para-substituted aromatic diamine; a heterocyclic diamine; an aliphatic diamine; and a solid blowing agent. The blowing agent is added to said precursor in a concentration which is sufficient to effect at least one of the following attributes of the foam: cell size, proportion of open cells, cell density, and indentation load deflection.

  17. Agent oriented programming

    NASA Technical Reports Server (NTRS)

    Shoham, Yoav

    1994-01-01

    The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

  18. Agility: Agent - Ility Architecture

    DTIC Science & Technology

    2002-10-01

    Figure 2: Overview of eGents 9 Specific scientific and engineering subgoals were: • develop a lightweight agent system that uses email- based ...applets makes them hard to operate over corporate firewalls. eGents e - mail based ACL bus imposes fewer requirements on agents that use it, and firewalls...do not pose a problem for an e - mail based ACL bus. While applets limit 35 JATLites range of applications, they also make JATlite easy to deploy

  19. Surface-active agents from the group of polyoxyethylated glycerol esters of fatty acids. Part III. Surface activity and solubilizing properties of the products of oxyethylation of lard (Adeps suillus, F.P. VIII) in the equilibrium system in relation to lipophilic therapeutic agents (class II and III of BCS).

    PubMed

    Nachajski, Michał J; Piotrowska, Jowita B; Kołodziejczyk, Michał K; Lukosek, Marek; Zgoda, Marian M

    2013-01-01

    Research was conducted into the solubilization processes of diclofenac, ibuprofen, ketoprofen and naproxen in equilibrium conditions in the environment of aqueous solutions of oxyethylated lard's fractions (Adeps suillus, Polish Pharmacopoeia VIII). The determined thermodynamic (cmc, deltaGm(0)) and hydrodynamic (R0, R(obs), omega, M(eta)) parameters characterizing the micelle of the solubilizer and the adduct demonstrate that lipophilic therapeutic agents are adsorbed in a palisade structure of the micelle due to a topologically created so-called "lipophilic adsorption pocket". This shows that the hydrophilicity of the micelle and the adsorption layer decreases at the phase boundary, which is confirmed by the calculated values of coefficients A(m) and r x (a). The results obtained indicate the possibility of making use of the class of non-ionic surfactants which are not ksenobiotics for the modification of the profile of solid oral dosage forms with lipophilic therapeutic agents from the II class of Biopharmaceutics Classification System (BCS).

  20. Host modulation by therapeutic agents

    PubMed Central

    Elavarasu, Sugumari; Sekar, Santhosh; Murugan, Thamaraiselvan

    2012-01-01

    Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, nitrous oxide (NO) synthase inhibitors, recombinant human interleukin-11 (rhIL-11), omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA), mitogen-activated protein kinase (MAPK) inhibitors, nuclear factor-kappa B (NF-kb) inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α) are some of the therapeutic agents that have host modulation properties. PMID:23066265

  1. The role of trefoil factor family in apparently healthy subjects administrated gastroprotective agents for the primary prevention of gastrointestinal injuries from low-dose acetylsalicylic acid: a preliminary study.

    PubMed

    Kawai, Takashi; Takagi, Yu; Fukuzawa, Mari; Yamagishi, Tetsuya; Goto, Shinya

    2011-09-01

    It is well-known that acetylsalicylic acid induces gastrointestinal complication. Recently, trefoil factor family has been reported as a mucosal protective factor. We focused on trefoil factor family as one of defensive system for gastrointestinal injuries. The aim of this trial was to evaluate trefoil factor family levels in the serum of healthy subjects with low-dose acetylsalicylic acid. Low-dose acetylsalicylic acid with placebo or proton pump inhibitor or rebamipide were administered in 30 healthy subjects. Transnasal endoscopy was performed at 0, 24 h, 3 and 7 day. Changing of trefoil factor family (1,2,3) and numbers of gastric injuries were evaluated. The numbers of gastric injuries were significantly increased in the placebo group at 3 and 7 days. Injuries in the proton pump inhibitor group were not induced, in the rebamipide group were slightly induced. Trefoil factor family level in the placebo group were decreased in 3 and 7 days compared with prior to starting the trial. Trefoil factor family may have an important association with acetylsalicylic acid-induced gastrointestinal damage. Proton pump inhibitor and rebamipide prevented low-dose acetylsalicylic acid-induced gastrointestinal complications compared with the placebo group.

  2. A review of responsive MRI contrast agents: 2005–2014

    PubMed Central

    Hingorani, Dina V.; Bernstein, Adam S.; Pagel, Mark D.

    2014-01-01

    This review focuses on MRI contrast agents that are responsive to a change in a physiological biomarker. The response mechanisms are dependent on six physicochemical characteristics, including the accessibility of water to the agent, tumbling time, proton exchange rate, electron spin state, MR frequency, or superparamagnetism of the agent. These characteristics can be affected by changes in concentrations or activities of enzymes, proteins, nucleic acids, metabolites, or metal ions, or changes in redox state, pH, temperature, or light. A total of 117 examples are presented, including examples that employ nuclei other than 1H, which attests to the creativity of multidisciplinary research efforts to develop responsive MRI contrast agents. PMID:25355685

  3. 9 CFR 121.4 - Overlap select agents and toxins.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  4. Compaction agent clarification of microbial lysates

    NASA Technical Reports Server (NTRS)

    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.

  5. Sunscreening agents: a review.

    PubMed

    Latha, M S; Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B R

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents.

  6. Agent independent task planning

    NASA Technical Reports Server (NTRS)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  7. Agents from amphibians with anticancer properties.

    PubMed

    Lu, Chuang-Xin; Nan, Ke-Jun; Lei, Yan

    2008-11-01

    Amphibians have been found to be a source of agents with anticancer properties. Bufalin, for example, is an anticancer agent that may induce apoptosis by its interaction with other genes and cellular components. Certain peptides with anticancer activities have been found in amphibian skin; they include magainins, aureins, citropin 1.1 and gaegurins. These peptides may exert a cytotoxic effect on human cancer cells through various mechanisms. Onconase, amphinase, cSBL (sialic acid-binding lectin purified from Rana catesbeiana eggs) and jSBL (sialic acid-binding lectin purified from Rana japonica eggs), which belong to the RNase A family, were purified from the oocyte cells and eggs of three amphibians, and they induce cytotoxicity by degrading cellular RNA. This paper discusses the medical and pharmaceutical significance of products derived from amphibians.

  8. Determination of sequestering agents in cosmetics and synthetic detergents by high-performance liquid chromatography with ultraviolet detection.

    PubMed

    Kemmei, Tomoko; Kodama, Shuji; Yamamoto, Atsushi; Inoue, Yoshinori; Hayakawa, Kazuichi

    2007-11-09

    Using a fast reversible reaction of aminopolycarboxylic acids (APCAs) into Fe(III)-APCA complexes in the presence of Fe(III) ions, seven kinds of APCAs [nitrilotriacetate (NTA), N-(2-hydroxyethyl)ethylenediamine-triacetate (HEDTA), ethylenediamine-tetraacetate (EDTA), 1,3-propanediamine-tetraacetate (PDTA), diethylenetriamine-pentaacetate (DTPA), 1,2-diaminopropane-tetraacetate (MeEDTA), and O,O'-bis(2-aminoethyl)ethyleneglycol-tetraacetate (GEDTA)] in cosmetics and synthetic detergents were separated on two reversed-phase C30 columns connected in series and detected with ultraviolet detection. Simple pretreatment, consisted of thousand times dilution of samples and addition of 100 microl of the Fe(III) solution containing 10 mM Fe(III) chloride and 0.5 M sulfuric acid to 10 ml of diluted samples, permitted the determination of APCAs in cosmetics and synthetic detergents at concentration level of 0.1 mM, except 0.3 mM for GEDTA. APCAs except GEDTA could be detected at concentration level of 0.03 mM and GEDTA could be detected at concentration level of 0.09 mM. Good recoveries (95-110%) were obtained for each APCA by the standard addition method on two diluted samples with high accuracy (RSD 0.2-9.1%). Three APCAs (EDTA, HEDTA and NTA) were detected in various concentrations in cosmetics and synthetic detergents and the other APCAs were not detected in any of the samples. This method requires no tedious pretreatment and takes only 15 min for one analysis, so it is useful for determination of APCAs.

  9. [Preparation of antineoplastic agents].

    PubMed

    Descoutures, J-M

    2006-01-01

    In the last fifteen years, the preparation of antineoplastic agents has tended to be centralized in the hospital pharmacy for two main reasons: to enable better protection for the staff, to enable better safety for the patient. The consequences of this organization have led to standardization of techniques, implementation of a quality system and also a better use of antineoplastic agents. After protocols have been standardized by the physician and validated by the pharmacist, four main steps are necessary: phamaceutical validation of the prescription, preparation of IV admixtures according to a production file, control of the final product, dispatching of the preparation to the patient. Computer-controlled processes guarantee the safety of these different steps. The centralized preparations are made either with a vertical laminar flow hood or with an isolator. With the implementation of the National Cancer Plan, antineoplastic agents for patients on home treatments will also be prepared in centralized hospital pharmacies.

  10. Polyphenols as antimicrobial agents.

    PubMed

    Daglia, Maria

    2012-04-01

    Polyphenols are secondary metabolites produced by higher plants, which play multiple essential roles in plant physiology and have potential healthy properties on human organism, mainly as antioxidants, anti-allergic, anti-inflammatory, anticancer, antihypertensive, and antimicrobial agents. In the present review the antibacterial, antiviral, and antifungal activities of the most active polyphenol classes are reported, highlighting, where investigated, the mechanisms of action and the structure-activity relationship. Moreover, considering that the microbial resistance has become an increasing global problem, and there is a compulsory need to find out new potent antimicrobial agents as accessories to antibiotic therapy, the synergistic effect of polyphenols in combination with conventional antimicrobial agents against clinical multidrug-resistant microorganisms is discussed.

  11. Metabolism-blocked antifolates as potential anti-rheumatoid arthritis agents: 4-amino-4-deoxy-5,8,10-trideazapteroyl-d,l-4'-methyleneglutamic acid (CH-1504) and its analogs.

    PubMed

    McGuire, John J; Haile, William H

    2009-04-01

    4-Amino-4-deoxy-5,8,10-trideazapteroyl-d,l-4'-methyleneglutamic acid (CH-1504) is the prototype of a potentially therapeutically more selective class of antifolates for rheumatoid arthritis treatment. This class is characterized by retention of dihydrofolate reductase (DHFR; EC 1.5.1.3) as their locus of action and transport by the reduced folate carrier (RFC; SLC19A1), but their lack of metabolism by known pathways of antifolate (e.g., methotrexate (MTX)) metabolism. Five new CH-1504 analogs (CHL-001-CHL-005) were synthesized and diastereomers of CH-1504 itself were obtained by preparative chiral HPLC; all were characterized biochemically. The analogs are not metabolized by aldehyde oxidase (EC 1.2.3.1), carboxypeptidase G2 (EC 3.4.17.11), or (excepting CHL-003) folylpolyglutamate synthetase (EC 6.3.2.17) and thus, unlike MTX, are "metabolism-blocked". All analogs are potent DHFR inhibitors; several are nearly as potent as MTX or CH-1504. Each analog uses the RFC for transport, although with varying apparent affinities. In contrast, each weakly inhibits other enzymes of folate metabolism relevant to rheumatoid arthritis therapy (thymidylate synthase (EC 2.1.1.45), two formyltransferases of purine biosynthesis (EC 2.1.2.2 and EC 2.1.2.3), and 5,10-methylenetetrahydrofolate reductase (EC 1.5.1.20)). Biochemical characterization showed one 4'-diastereomer of racemic CH-1504 was significantly more active than the other. Based on literature data concerning the effect of d- and l-glutamic acid substitution on antifolate activity, it is likely that the diastereomer containing l-4'-methylene-glutamic acid is the more active. Because of concern about potential pharmacokinetic and biochemical effects of d-4'-methylene-glutamic acid-containing species, these data suggest that future analogs should contain only l-4'-methylene-glutamic acid. Overall, these data provide several interesting new leads for preclinical development.

  12. Azelaic acid.

    PubMed

    Nazzaro-Porro, M

    1987-12-01

    This review is an update on the literature accumulated over the past 10 years following the original observation that azelaic acid, a naturally occurring and nontoxic C9 dicarboxylic acid, possesses significant biologic properties and a potential as a therapeutic agent. These studies have shown that azelaic acid is a reversible inhibitor of tyrosinase and other oxidoreductases in vitro and that it inhibits mitochondrial respiration. It can also inhibit anaerobic glycolysis. Both in vitro and in vivo it has an antimicrobial effect on both aerobic and anaerobic (Propionibacterium acnes) microorganisms. In tissue culture it exerts a dose- and time-dependent cytotoxic effect on malignant melanocytes, associated with mitochondrial damage and inhibition of deoxyribonucleic acid (DNA) synthesis. Tumoral cell lines not containing tyrosinase are equally affected. Normal cells in culture exposed to the same concentrations of the diacid that are toxic for tumoral cells are in general not damaged. Radioactive azelaic acid has been shown to penetrate tumoral cells at a higher level than normal cells of the corresponding line. Topically applied (a 20% cream), it has been shown to be of therapeutic value in skin disorders of different etiologies. Its beneficial effect on various forms of acne (comedogenic, papulopustular, nodulocystic) has been clearly demonstrated. Particularly important is its action on abnormal melanocytes, which has led to the possibility of obtaining good results on melasma and highly durable therapeutic responses on lentigo maligna. It is also capable of causing regression of cutaneous malignant melanoma, but its role in melanoma therapy remains to be investigated.(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Agent Persuasion Mechanism of Acquaintance

    NASA Astrophysics Data System (ADS)

    Jinghua, Wu; Wenguang, Lu; Hailiang, Meng

    Agent persuasion can improve negotiation efficiency in dynamic environment based on its initiative and autonomy, and etc., which is being affected much more by acquaintance. Classification of acquaintance on agent persuasion is illustrated, and the agent persuasion model of acquaintance is also illustrated. Then the concept of agent persuasion degree of acquaintance is given. Finally, relative interactive mechanism is elaborated.

  14. Model Checking Normative Agent Organisations

    NASA Astrophysics Data System (ADS)

    Dennis, Louise; Tinnemeier, Nick; Meyer, John-Jules

    We present the integration of a normative programming language in the MCAPL framework for model checking multi-agent systems. The result is a framework facilitating the implementation and verification of multi-agent systems coordinated via a normative organisation. The organisation can be programmed in the normative language while the constituent agents may be implemented in a number of (BDI) agent programming languages.

  15. [Surface-active agents from the group of polyoxyethylated glycerol esters of fatty acids. Part II. Chromatographic analysis and basic viscosity parameters as a estimate criterion of efficiency of catalytic oxyethylation of Lard's fractions (Adeps suillus FP VII)].

    PubMed

    Piotrowska, Jowita Barbara; Nachajski, Michał Jakub; Lukosek, Marek; Kosno, Jacek; Zgoda, Marian Mikołaj

    2011-01-01

    The catalytic oxyethylation products of Lard's fractions and Tweens--as a reference products, were analised by chromatographic analysis HPLC and GPC. The above part was determination average molecular weights dispersion (Mw I Mn) and the content of polyethylene glycols (PEG), which are obtained during catalytic oxyethylation, and determination iodine value of the product (L(J2)). Viscosity measurements were carried out by Ubelohde method and enabled determination of basic viscosity and hydrodynamic parameters. The obtained results indicate that, comparing reference products--polysorbates, Tweens, products of triglycerides oxyethylation contain significantly less, in some cases very small amount of polyethylene glycols (PEG), and also maintained a high amount of unsaturated fatty acids (oleic acid), which is proven by the iodine value. Numerical value n(s) /H2O/ confirms important disparity of micells palisad structure, which are created based on oxyethylated triglycerides nTE = 40. That indicates significant solubilization possibilities of their aqueous solutions Cexp < or = Cmc.

  16. Remote Agent Experiment

    NASA Technical Reports Server (NTRS)

    Benard, Doug; Dorais, Gregory A.; Gamble, Ed; Kanefsky, Bob; Kurien, James; Millar, William; Muscettola, Nicola; Nayak, Pandu; Rouquette, Nicolas; Rajan, Kanna; Norvig, Peter (Technical Monitor)

    2000-01-01

    Remote Agent (RA) is a model-based, reusable artificial intelligence (At) software system that enables goal-based spacecraft commanding and robust fault recovery. RA was flight validated during an experiment on board of DS1 between May 17th and May 21th, 1999.

  17. Can Subscription Agents Survive?

    ERIC Educational Resources Information Center

    Tuttle, Marcia

    1985-01-01

    With the saturation of traditional markets for their services, subscription agents have evolved from orders and invoices to serving customers by communicating with librarians and publishers and making automated and paper products available. Magazine fulfillment centers, publisher discounts, and electronic publishing will influence the subscription…

  18. E-Learning Agents

    ERIC Educational Resources Information Center

    Gregg, Dawn G.

    2007-01-01

    Purpose: The purpose of this paper is to illustrate the advantages of using intelligent agents to facilitate the location and customization of appropriate e-learning resources and to foster collaboration in e-learning environments. Design/methodology/approach: This paper proposes an e-learning environment that can be used to provide customized…

  19. Complexation of Am(III) and Nd(III) by 1,10-Phenanthroline-2,9-Dicarboxylic Acid

    SciTech Connect

    Ogden, Mark D.; Sinkov, Sergey I.; Nilsson, Mikael; Lumetta, Gregg J.; Hancock, Robert D.; Nash, Ken L.

    2013-01-01

    The complexant 1,10-phenanthroline-2,9-dicarboxylic acid (PDA) is a planar tetradentate ligand that is more preorganized for metal complexation than its unconstrained analogue ethylendiiminodiacetic acid (EDDA). Furthermore, the backbone nitrogen atoms of PDA are aromatic, hence are softer than the aliphatic amines of EDDA. It has been hypothesized that PDA will selectively bond to trivalent actinides over lanthanides. In this report, the results of spectrophotometric studies of the complexation of Nd(III) and Am(III) by PDA are reported. Because the complexes are moderately stable, it was necessary to conduct these titrations using competitive equilibrium methods, competitive cation omplexing between PDA and diethylenetriaminepentaacetic acid, and competition between ligand protonation and complex formation. Stability constants and ligand protonation constants were determined at 0.1 mol/L ionic strength and at 0.5 mol/L ionic strength nitrate media at 21 ± 1 C. The stability constants are lower than those predicted from first principles and speciation calculations indicate that Am(III) selectivity over Nd(III) is less than that exhibited by 1,10-phenanthroline.

  20. Fatty acid as structure directing agent for controlled secondary growth of CoFe2O4 nanoparticles to achieve mesoscale assemblies: A facile approach for developing hierarchical structures

    NASA Astrophysics Data System (ADS)

    Saikia, K.; Kaushik, S. D.; Sen, D.; Mazumder, S.; Deb, P.

    2016-08-01

    Mesoscale hierarchical assemblies have emerged out as a new class of structures between fine dimension nanoparticles and bulk structures, having distinctly different physical properties from either side. Controlling the self-assembly process of primary nanoparticles and subsequent secondary growth mechanism is the key aspect for achieving such ordered structures. In this work, we introduce a new insight on achieving hierarchical assemblies of CoFe2O4 nanoparticles based on the temporal stability of the primary nanoparticles, where, the growth and stability of the primary particles are controlled by using oleic acid. It is found that the developed particles, at a critical concentration of oleic acid, prefer a secondary growth process, rather than promoting their individual growth. Domination of the attractive hydrophobic interaction over steric repulsion among the primary particles at this critical concentration of oleic acid is found to be the key factor for the initial aggregation of the primary particles, which eventually leads to the formation of spherical hierarchical assemblies via oriented attachment. It is also realized that the extremely well or poor stability conditions of the primary particles do not allow this secondary growth process. Estimated values of Co2+ distribution factor show that the cation distribution factor of CoFe2O4 system is not affected by the nature of dominant growth processes, when these are controlled. Interestingly, magnetic measurements reflect the stronger interparticle interaction in the hierarchical system and high magnetic moment values at low magnetic field.