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Sample records for isocratic elution utilizing

  1. Thermodynamic modeling of protein retention in mixed-mode chromatography: An extended model for isocratic and dual gradient elution chromatography.

    PubMed

    Lee, Yi Feng; Graalfs, Heiner; Frech, Christian

    2016-09-16

    An extended model is developed to describe protein retention in mixed-mode chromatography based on thermodynamic principles. Special features are the incorporation of pH dependence of the ionic interaction on a mixed-mode resin and the addition of a water term into the model which enables one to describe the total number of water molecules released at the hydrophobic interfaces upon protein-ligand binding. Examples are presented on how to determine the model parameters using isocratic elution chromatography. Four mixed-mode anion-exchanger prototype resins with different surface chemistries and ligand densities were tested using isocratic elution of two monoclonal antibodies at different pH values (7-10) and encompassed a wide range of NaCl concentrations (0-5M). U-shape mixed-mode retention curves were observed for all four resins. By taking into account of the deprotonation and protonation of the weak cationic functional groups in these mixed-mode anion-exchanger prototype resins, conditions which favor protein-ligand binding via mixed-mode strong cationic ligands as well as conditions which favor protein-ligand binding via both mixed-mode strong cationic ligands and non-hydrophobic weak cationic ligands were identified. The changes in the retention curves with pH, salt, protein, and ligand can be described very well by the extended model using meaningful thermodynamic parameters like Gibbs energy, number of ionic and hydrophobic interactions, total number of released water molecules as well as modulator interaction constant. Furthermore, the fitted model parameters based on isocratic elution data can also be used to predict protein retention in dual salt-pH gradient elution chromatography. PMID:27554024

  2. Normalized Elution Time Prediction Utility

    2011-02-17

    This program is used to compute the predicted normalized elution time (NET) for a list of peptide sequences. It includes the Kangas/Petritis neural network trained model, the Krokhin hydrophobicity model, and the Mant hydrophobicity model. In addition, it can compute the predicted strong cation exchange (SCX) fraction (on a 0 to 1 scale) in which a given peptide will appear.

  3. The utility of accurate mass and LC elution time information in the analysis of complex proteomes

    SciTech Connect

    Norbeck, Angela D.; Monroe, Matthew E.; Adkins, Joshua N.; Anderson, Kevin K.; Daly, Don S.; Smith, Richard D.

    2005-08-01

    Theoretical tryptic digests of all predicted proteins from the genomes of three organisms of varying complexity were evaluated for specificity and possible utility of combined peptide accurate mass and predicted LC normalized elution time (NET) information. The uniqueness of each peptide was evaluated using its combined mass (+/- 5 ppm and 1 ppm) and NET value (no constraint, +/- 0.05 and 0.01 on a 0-1 NET scale). The set of peptides both underestimates actual biological complexity due to the lack of specific modifications, and overestimates the expected complexity since many proteins will not be present in the sample or observable on the mass spectrometer because of dynamic range limitations. Once a peptide is identified from an LCMS/MS experiment, its mass and elution time is representative of a unique fingerprint for that peptide. The uniqueness of that fingerprint in comparison to that for the other peptides present is indicative of the ability to confidently identify that peptide based on accurate mass and NET measurements. These measurements can be made using HPLC coupled with high resolution MS in a high-throughput manner. Results show that for organisms with comparatively small proteomes, such as Deinococcus radiodurans, modest mass and elution time accuracies are generally adequate for peptide identifications. For more complex proteomes, increasingly accurate easurements are required. However, the majority of proteins should be uniquely identifiable by using LC-MS with mass accuracies within +/- 1 ppm and elution time easurements within +/- 0.01 NET.

  4. Hydrogen sulfide production by sulfate-reducing bacteria utilizing additives eluted from plastic resins.

    PubMed

    Tsuchida, Daisuke; Kajihara, Yusuke; Shimidzu, Nobuhiro; Hamamura, Kengo; Nagase, Makoto

    2011-06-01

    In the present study it was demonstrated that organic additives eluted from plastic resins could be utilized as substrates by sulfate-reducing bacteria. Two laboratory-scale experiments, a microcosm experiment and a leaching experiment, were conducted using polyvinyl chloride (PVC) as a model plastic resin. In the former experiment, the conversion of sulfate to sulfide was evident in microcosms that received plasticized PVC as the sole carbon source, but not in those that received PVC homopolymer. Additionally, dissolved organic carbon accumulated only in microcosms that received plasticized PVC, indicating that the dissolved organic carbon originated from additives. In the leaching experiment, phenol and bisphenol A were found in the leached solutions. These results suggest that the disposal of waste plastics in inert waste landfills may result in the production of H(2)S.

  5. Utility of drug-eluting stents in complex lesions and high-risk patients.

    PubMed

    Nikolsky, Eugenia; Stone, Gregg W

    2007-02-01

    Drug-eluting stents represent a breakthrough technology designed to deliver high concentrations of a bioactive agent locally to an atherosclerotic lesion, thereby minimizing systemic side effects of the drug. The safety and efficacy of drug-eluting stents have clearly been demonstrated in noncomplex lesions. This article presents an evidence-based analysis of the current experience with CYPHER sirolimus-eluting stents (Cordis Corp., Miami Lakes, FL) and TAXUS paclitaxel-eluting stents (Boston Scientific, Natick, MA) in a broad spectrum of high-risk and/or complex subsets of patients and lesions, including those with diabetes mellitus, multivessel disease, diffuse disease, very small vessels, lesions in saphenous vein grafts, chronic total occlusions, in-stent restenosis, ostial and bifurcation lesions, unprotected left main disease, and acute myocardial infarction. Emerging data in several of these subsets suggest that drug-eluting stents are safe and effective, and their use may currently be recommended, whereas in other groups of patients and lesions the efficacy and/or safety of drug-eluting stents remains to be determined, thus warranting caution. It is anticipated that penetration of drug-eluting stents will continue to increase, and fewer patients will require surgical revascularization to achieve sustained event-free survival.

  6. Mass transfer coefficients determination from linear gradient elution experiments.

    PubMed

    Pfister, David; Morbidelli, Massimo

    2015-01-01

    A procedure to estimate mass transfer coefficients in linear gradient elution chromatography is presented and validated by comparison with experimental data. Mass transfer coefficients are traditionally estimated experimentally through the van Deemter plot, which represents the HETP as a function of the fluid velocity. Up to now, the HETP was obtained under isocratic elution conditions. Unfortunately, isocratic elution experiments are often not suitable for large biomolecules which suffer from severe mass transfer hindrances. Yamamoto et al. were the first to propose a semi-empirical equation to relate HETPs measured from linear gradient elution experiments to those obtained under isocratic conditions [7]. Based on his pioneering work, the approach presented in this work aims at providing an experimental procedure supported by simple equations to estimate reliable mass transfer parameters from linear gradient elution chromatographic experiments. From the resolution of the transport model, we derived a rigorous analytical expression for the HETP in linear gradient elution chromatography.

  7. Simple isocratic method for simultaneous determination of caffeine and catechins in tea products by HPLC.

    PubMed

    Fernando, Chamira Dilanka; Soysa, Preethi

    2016-01-01

    Tea is a popular beverage almost all over the world. Many studies show that tea consumption is closely associated with positive health impact. Most of the HPLC methods used for the determination of tea constituents include gradient elution systems which involve expensive instrumentation. The objective of this study was to develop a simple, rapid precise and low cost HPLC method for the separation and quantification of catechins and caffeine in tea (Camellia sinensis). The method utilizes a phenyl column (2.1 × 150 mm) with a UV-detector (280 nm) where excellent chromatographic separation of tea components i.e. gallic acid (GA), caffeine (Caf), epicatechin (EC) and (-)-epigallocatechin gallate (EGCG) was achieved. The isocratic elution system of acetonitrile, glacial acetic acid and deionized water (8:1:91 v/v/v) at a flow rate of 0.5 mL/min was involved. This method produced excellent accuracy and precision. Within run and between run precision was less than 7.5 %. The equations for calibration curves were y = 0.117 (±0.010)x + 0.173 (±0.024), y = 0.100 (±0.003)x + 0.045 (±0.019), y = 0.016 (±0.001)x + 0.006 (±0.004), y = 0.025 (±0.001)x-0.025 (±0.007) for GA, Caf, EC and EGCG respectively. The method validation parameters prove that the method is efficient, a simple and adequate for the quantitative determination of principal components in tea samples. PMID:27429880

  8. Differences in utilization of drug-eluting stents by race and payer.

    PubMed

    Hannan, Edward L; Racz, Michael; Walford, Gary; Clark, Luther T; Holmes, David R; King, Spencer B; Sharma, Samin

    2007-10-15

    Numerous disparities in access to health care by race and gender have been identified in the literature. This study examines differences in the use of drug-eluting stents (DES) versus bare-metal stents (BMS) by race, payer, and income level. Data from New York State's Percutaneous Coronary Intervention Reporting System from July 2003 to December 2004 were used to examine use of DES (20,165 patients) relative to BMS (4,547 patients) by race, payer, and annual income level, controlling for a variety of patient and hospital characteristics. African-Americans were found to be less likely to receive DES than other races between July 2003 and March 2004 (adjusted odds ratio [OR] 0.56, 95% confidence interval [CI] 0.50 to 0.65) and between April 2004 and December 2004 (adjusted OR 0.74, 95% CI 0.61 to 0.90). These disparities were reduced (respective adjusted ORs 0.67, 95% CI 0.58 to 0.77 and 0.81, 95% CI 0.66 to 0.91) when controlling for admitting hospital and hospital volume, but were still significant. Medicaid/self-pay patients, and patients living in zip codes with median annual incomes between $20,000 and $30,000 were also less likely to receive DES in the first time period (adjusted respective ORs 0.80, 95% CI 0.68 to 0.93) and 0.85, 95% CI 0.75 to 0.96). In conclusion, African-Americans and low income groups receive DES less frequently than their counterparts compared with BMS. This is related to the hospitals where they are admitted, but not entirely.

  9. Simultaneous analysis of heparosan oligosaccharides by isocratic liquid chromatography with charged aerosol detection/mass spectrometry.

    PubMed

    Ji, Xiaohu; Hu, Guixin; Zhang, Qiongyan; Wang, Fengshan; Liu, Chunhui

    2016-11-01

    Uncovering the biological roles of heparosan oligosaccharides requires a simple and robust method for their separation and identification. We reported on systematic investigations of the retention behaviors of synthetic heparosan oligosaccharides on porous graphitic carbon (PGC) column by HPLC with charged aerosol detection. Oligosaccharides were strongly retained by PGC material in water-acetonitrile mobile phase, and eluted by trifluoroacetic acid occurring as narrow peaks. Addition of small fraction of methanol led to better selectivity of PGC to oligosaccharides than acetonitrile modifier alone, presumably, resulting from displacement of methanol to give different chemical environment at the PGC surface. Van't-Hoff plots demonstrated that retention behaviors highly depended on the column temperature and oligosaccharide moieties. By implementing the optimal MeOH content and temperature, a novel isocratic elution method was successfully developed for baseline resolution and identification of seven heparosan oligosaccharides using PGC-HPLC-CAD/MS. This approach allows for rapid analysis of heparosan oligosaccharides from various sources. PMID:27516280

  10. Stochastic approach for an unbiased estimation of the probability of a successful separation in conventional chromatography and sequential elution liquid chromatography.

    PubMed

    Ennis, Erin J; Foley, Joe P

    2016-07-15

    A stochastic approach was utilized to estimate the probability of a successful isocratic or gradient separation in conventional chromatography for numbers of sample components, peak capacities, and saturation factors ranging from 2 to 30, 20-300, and 0.017-1, respectively. The stochastic probabilities were obtained under conditions of (i) constant peak width ("gradient" conditions) and (ii) peak width increasing linearly with time ("isocratic/constant N" conditions). The isocratic and gradient probabilities obtained stochastically were compared with the probabilities predicted by Martin et al. [Anal. Chem., 58 (1986) 2200-2207] and Davis and Stoll [J. Chromatogr. A, (2014) 128-142]; for a given number of components and peak capacity the same trend is always observed: probability obtained with the isocratic stochastic approachisocratic simulations compared to the gradient simulations with the same peak capacity. When the stochastic results are applied to conventional HPLC and sequential elution liquid chromatography (SE-LC), the latter is shown to provide much greater probabilities of success for moderately complex samples (e.g., PHPLC=31.2% versus PSE-LC=69.1% for 12 components and the same analysis time). For a given number of components, the density of probability data provided over the range of peak capacities is sufficient to allow accurate interpolation of probabilities for peak capacities not reported, <1.5% error for saturation factors <0.20. Additional applications for the stochastic approach include isothermal and programmed-temperature gas chromatography.

  11. Effect of pre- and post-column band broadening on the performance of high-speed chromatography columns under isocratic and gradient conditions.

    PubMed

    Vanderlinden, Kim; Broeckhoven, Ken; Vanderheyden, Yoachim; Desmet, Gert

    2016-04-15

    We report on the results of an experimental and theoretical study of the effect of the extra-column band broadening (ECBB) on the performance of narrow-bore columns filled with the smallest particles that are currently commercially available. Emphasis is on the difference between the effect of ECBB under gradient and isocratic conditions, as well as on the ability to model and predict the ECBB effects using well-established band broadening expressions available from the theory of chromatography. The fine details and assumptions that need to be taken into account when using these expressions are discussed. The experiments showed that, the steeper the gradient, the more pronounced the extra-column band broadening losses become. Whereas the pre-column band broadening can in both isocratic and gradient elution be avoided by playing on the possibilities to focus the analytes on top of the column (e.g. by using the POISe injection method when running isocratic separations), the post-column extra-column band broadening is inescapable in both cases. Inducing extra-column band broadening by changing the inner diameter of the post-column tubing from 65 to 250 μm, we found that all peaks in the chromatogram are strongly affected (around a factor of 1.9 increase in relative peak width) when running steep gradients, while usually only the first eluting peak was affected in the isocratic mode or when running shallow gradients (factor 1.6-1.8 increase in relative peak width for the first eluting analyte).

  12. Isocratic and gradient impedance plot analysis and comparison of some recently introduced large size core-shell and fully porous particles.

    PubMed

    Vanderheyden, Yoachim; Cabooter, Deirdre; Desmet, Gert; Broeckhoven, Ken

    2013-10-18

    The intrinsic kinetic performance of three recently commercialized large size (≥4μm) core-shell particles packed in columns with different lengths has been measured and compared with that of standard fully porous particles of similar and smaller size (5 and 3.5μm, respectively). The kinetic performance is compared in both absolute (plot of t0 versus the plate count N or the peak capacity np for isocratic and gradient elution, respectively) and dimensionless units. The latter is realized by switching to so-called impedance plots, a format which has been previously introduced (as a plot of t0/N(2) or E0 versus Nopt/N) and has in the present study been extended from isocratic to gradient elution (where the impedance plot corresponds to a plot of t0/np(4) versus np,opt(2)/np(2)). Both the isocratic and gradient impedance plot yielded a very similar picture: the clustered impedance plot curves divide into two distinct groups, one for the core-shell particles (lowest values, i.e. best performance) and one for the fully porous particles (highest values), confirming the clear intrinsic kinetic advantage of core-shell particles. If used around their optimal flow rate, the core-shell particles displayed a minimal separation impedance that is about 40% lower than the fully porous particles. Even larger gains in separation speed can be achieved in the C-term regime.

  13. A salt-free isocratic high-pressure liquid chromatographic method for the quantitation of benzodiazepines in serum.

    PubMed

    Tai, H L; Osiewicz, R J; Bofinger, D P

    1993-06-01

    A simple, rapid high-pressure liquid chromatography (HPLC) method was developed for detecting and quantifying benzodiazepines in serum. Seven major benzodiazepines were extracted from spiked serum samples using solid-phase extraction with prazepam as the internal standard. The eluted drugs were then resolved isocratically by HPLC within 11 min using a reversed-phase C8 column with a mobile phase consisting of acetonitrile, methanol, water, and perchloric acid. All drugs gave responses that varied linearly with concentration over the ranges studied. Within-day imprecision (CV) varied from 3.9 to 14.9%, day-to-day CV from 4.8 to 17.0%, absolute recoveries from 67% to 114%, and detection limits from 10 to 110 ng/mL. Tricyclic antidepressants did not interfere, and clinical results were in good agreement with those obtained by a gas chromatographic method. The advantage of this method is that it uses a salt-free isocratic mobile phase that can be easily manipulated to effect difficult benzodiazepine separations.

  14. A strategy for the systematic development of a liquid chromatographic mass spectrometric screening method for polymer electrolyte membrane degradation products using isocratic and gradient phase optimized liquid chromatography.

    PubMed

    Zedda, M; Tuerk, J; Teutenberg, T; Peil, S; Schmidt, T C

    2009-12-18

    Within the scope of research for target and non-target LC-MS/MS analysis of membrane degradation products of polymer electrolyte membrane fuel cells, a systematic method development for the separation of structurally similar compounds was performed by phase optimized liquid chromatography. Five different stationary phases with different selectivities were used. Isocratic separation for 4-hydroxybenzoic acid, isophthalic acid, terephthalic acid, 4-hydroxybenzaldehyde and 4-formylbenzoic acid was achieved on a C18 and a Phenyl phase. Using the PRISMA model the separation efficiency was optimized. This was achieved on a serially connected mixed stationary phase composed of 30 mm C18, 150 mm Phenyl and 60 mm C30. For the LC-MS screening of unknown degradation products from polymer electrolyte membranes in the product water of a fuel cell, a solvent gradient is mandatory for less polar or later eluting compounds. By means of 4-mercaptobenzoic acid it could be shown that a solvent gradient can be applied in order to elute later eluting compounds in a short time. The adaptability of this method for the qualitative analysis by target and non-target LC-MS/MS screening has been shown by means of 4-hydroxybenzoic acid. The combination of solvent gradient and isocratic conditions makes this approach attractive for the purpose of a screening method for known and unknown analytes in a water sample.

  15. Gradient elution capillary electrochromatography and hyphenation with nuclear magnetic resonance.

    PubMed

    Gfrörer, P; Schewitz, J; Pusecker, K; Tseng, L H; Albert, K; Bayer, E

    1999-01-01

    Coupling of gradient capillary electrochromatography (gradient CEC) and capillary zone electrophoresis (CZE) with nuclear magnetic resonance spectroscopy (NMR) was performed using a recently developed capillary NMR interface. This technique was applied for the analysis of pharmaceuticals and food. An analgesic was investigated using isocratic and gradient continuous-flow CEC-NMR. Comparison of the results demonstrated the superiority of gradient CEC over isocratic CEC. Aspartame and caffeine, both ingredients of soft beverages, were separated and analyzed by continuous flow CZE-NMR. The order of elution could be reversed by altering the pH. This reversal led to an increased sample concentration in the NMR detection cell, thus allowing the acquisition of a totally correlated spectroscopy (TOCSY) two-dimensional (2-D) spectrum of the synthetic peptide aspartame. PMID:10065951

  16. Gradient elution capillary electrochromatography and hyphenation with nuclear magnetic resonance.

    PubMed

    Gfrörer, P; Schewitz, J; Pusecker, K; Tseng, L H; Albert, K; Bayer, E

    1999-01-01

    Coupling of gradient capillary electrochromatography (gradient CEC) and capillary zone electrophoresis (CZE) with nuclear magnetic resonance spectroscopy (NMR) was performed using a recently developed capillary NMR interface. This technique was applied for the analysis of pharmaceuticals and food. An analgesic was investigated using isocratic and gradient continuous-flow CEC-NMR. Comparison of the results demonstrated the superiority of gradient CEC over isocratic CEC. Aspartame and caffeine, both ingredients of soft beverages, were separated and analyzed by continuous flow CZE-NMR. The order of elution could be reversed by altering the pH. This reversal led to an increased sample concentration in the NMR detection cell, thus allowing the acquisition of a totally correlated spectroscopy (TOCSY) two-dimensional (2-D) spectrum of the synthetic peptide aspartame.

  17. Simple Isocratic HPLC Method for Determination of Enantiomeric Impurity in Besifloxacin Hydrochloride.

    PubMed

    Kumar, G Pradeep; Srivastava, Vishal; Khandelwal, Kiran; Kumar, Rajesh; Hiriyanna, S G; Kumar, Ajay; Kumar, Pramod

    2016-09-01

    Besifloxacin is a unique chiral broad-spectrum flouroquinolone used in the treatment of bacterial conjunctivitis. R-form of besifloxacin hydrochloride shows higher antibacterial activity as compared to the S-isomer. Therefore, it is necessary to establish chiral purity. To establish chiral purity a high-performance liquid chromatography (HPLC) method for determination of R-besifloxacin and S-besifloxacin (BES impurity A) was developed and validated for in-process quality control and stability studies. The analytical performance parameters such as linearity, precision, accuracy, specificity, limit of detection (LOD), and lower limit of quantification (LOQ) were determined according to International Council for Harmonization ICH Q2(R1) guidelines. HPLC separation was achieved on Chiralpak AD-H (250 x 4.6 mm, 5 μm) column using n-heptane: ethanol: ethylenediamine: acetic acid (800:200:0.5:0.5) (v/v/v/v) as the mobile phase in an isocratic elution. The eluents were monitored by UV/Visible detector at 290 nm. The resolution between S-isomer and besifloxacin hydrochloride was more than 2.0. Based on a signal-to-noise ratio of 3 and 10 the LOD of besifloxacin was 0.30 μg/mL, while the LOQ was 0.90 μg/mL. The calibration curves were linear in the range of 0.9-7.5 μg/mL. Precision of the method was established within the acceptable range. The method was suitable for the quality control enantiomeric impurity in besifloxacin hydrochloride. Chirality 28:628-632, 2016. © 2016 Wiley Periodicals, Inc. PMID:27563753

  18. Development of a fast isocratic LC-MS/MS method for the high-throughput analysis of pyrrolizidine alkaloids in Australian honey.

    PubMed

    Griffin, Caroline T; Mitrovic, Simon M; Danaher, Martin; Furey, Ambrose

    2015-01-01

    Honey samples originating from Australia were purchased and analysed for targeted pyrrolizidine alkaloids (PAs) using a new and rapid isocratic LC-MS/MS method. This isocratic method was developed from, and is comparable with, a gradient elution method and resulted in no loss of sensitivity or reduction in chromatographic peak shape. Isocratic elution allows for significantly shorter run times (6 min), eliminates the requirement for column equilibration periods and, thus, has the advantage of facilitating a high-throughput analysis which is particularly important for regulatory testing laboratories. In excess of two hundred injections are possible, with this new isocratic methodology, within a 24-h period which is more than 50% improvement on all previously published methodologies. Good linear calibrations were obtained for all 10 PAs and four PA N-oxides (PANOs) in spiked honey samples (3.57-357.14 µg l(-1); R(2) ≥ 0.9987). Acceptable inter-day repeatability was achieved for the target analytes in honey with % RSD values (n = 4) less than 7.4%. Limits of detection (LOD) and limits of quantitation (LOQ) were achieved with spiked PAs and PANOs samples; giving an average LOD of 1.6 µg kg(-1) and LOQ of 5.4 µg kg(-1). This method was successfully applied to Australian and New Zealand honey samples sourced from supermarkets in Australia. Analysis showed that 41 of the 59 honey samples were contaminated by PAs with the mean total sum of PAs being 153 µg kg(-1). Echimidine and lycopsamine were predominant and found in 76% and 88%, respectively, of the positive samples. The average daily exposure, based on the results presented in this study, were 0.051 µg kg(-1) bw day(-1) for adults and 0.204 µg kg(-1) bw day(-1) for children. These results are a cause for concern when compared with the proposed European Food Safety Authority (EFSA), Committee on Toxicity (COT) and Bundesinstitut für Risikobewertung (BfR - Federal Institute of Risk Assessment Germany) maximum

  19. Sequential elution process

    DOEpatents

    Kingsley, I.S.

    1987-01-06

    A process and apparatus are disclosed for the separation of complex mixtures of carbonaceous material by sequential elution with successively stronger solvents. In the process, a column containing glass beads is maintained in a fluidized state by a rapidly flowing stream of a weak solvent, and the sample is injected into this flowing stream such that a portion of the sample is dissolved therein and the remainder of the sample is precipitated therein and collected as a uniform deposit on the glass beads. Successively stronger solvents are then passed through the column to sequentially elute less soluble materials. 1 fig.

  20. Innovative Elution Processes for Recovering Uranium from Seawater

    SciTech Connect

    Wai, Chien; Tian, Guoxin; Janke, Christopher

    2014-05-29

    Utilizing amidoxime-based polymer sorbents for extraction of uranium from seawater has attracted considerable interest in recent years. Uranium collected in the sorbent is recovered typically by elution with an acid. One drawback of acid elution is deterioration of the sorbent which is a significant factor that limits the economic competitiveness of the amidoxime-based sorbent systems for sequestering uranium from seawater. Developing innovative elution processes to improve efficiency and to minimize loss of sorbent capacity become essential in order to make this technology economically feasible for large-scale industrial applications. This project has evaluated several elution processes including acid elution, carbonate elution, and supercritical fluid elution for recovering uranium from amidoxime-based polymer sorbents. The elution efficiency, durability and sorbent regeneration for repeated uranium adsorption- desorption cycles in simulated seawater have been studied. Spectroscopic techniques are used to evaluate chemical nature of the sorbent before and after elution. A sodium carbonate-hydrogen peroxide elution process for effective removal of uranium from amidoxime-based sorbent is developed. The cause of this sodium carbonate and hydrogen peroxide synergistic leaching of uranium from amidoxime-based sorbent is attributed to the formation of an extremely stable uranyl peroxo-carbonato complex. The efficiency of uranium elution by the carbonate-hydrogen peroxide method is comparable to that of the hydrochloric acid elution but damage to the sorbent material is much less for the former. The carbonate- hydrogen peroxide elution also does not need any elaborate step to regenerate the sorbent as those required for hydrochloric acid leaching. Several CO2-soluble ligands have been tested for extraction of uranium from the sorbent in supercritical fluid carbon dioxide. A mixture of hexafluoroacetylacetone and tri-n-butylphosphate shows the best result but uranium

  1. Quest for organic polymer-based monolithic columns affording enhanced efficiency in high performance liquid chromatography separations of small molecules in isocratic mode.

    PubMed

    Svec, Frantisek

    2012-03-01

    The separations of small molecules using columns containing porous polymer monoliths invented two decades ago went a long way from the very modest beginnings to the current capillary columns with efficiencies approaching those featured by their silica-based counterparts. This review article presents a variety of techniques that have been used to form capillary formats of monolithic columns with enhanced separation performance in isocratic elutions. The following text first describes the traditional approaches used for the preparation of efficient monoliths comprising variations in polymerization conditions including temperature as well as composition of monomers and porogenic solvents. Encouraging results of these experiments fueled research of completely new preparation methods such as polymerization to an incomplete conversion, use of single crosslinker, hypercrosslinking, and incorporation of carbon nanotubes that are described in the second part of the text. PMID:21816401

  2. Simultaneous separation of water- and fat-soluble vitamins in isocratic pressure-assisted capillary electrochromatography using a methacrylate-based monolithic column.

    PubMed

    Yamada, Hiroki; Kitagawa, Shinya; Ohtani, Hajime

    2013-06-01

    A method of simultaneous separation of water- and fat-soluble vitamins using pressure-assisted CEC with a methacrylate-based capillary monolithic column was developed. In the proposed method, water-soluble vitamins were mainly separated electrophoretically, while fat soluble-ones were separated chromatographically by the interaction with a methacrylate-based monolith. A mixture of six water-soluble and four fat-soluble vitamins was separated simultaneously within 20 min with an isocratic elution using 1 M formic acid (pH 1.9)/acetonitrile (30:70, v/v) containing 10 mM ammonium formate as a mobile phase. When the method was applied to a commercial multivitamin tablet and a spiked one, the vitamins were successfully analyzed, and no influence of the matrix contained in the tablet was observed.

  3. Fractionating power and outlet stream polydispersity in asymmetrical flow field-flow fractionation. Part I: isocratic operation.

    PubMed

    Williams, P Stephen

    2016-05-01

    Asymmetrical flow field-flow fractionation (As-FlFFF) has become the most commonly used of the field-flow fractionation techniques. However, because of the interdependence of the channel flow and the cross flow through the accumulation wall, it is the most difficult of the techniques to optimize, particularly for programmed cross flow operation. For the analysis of polydisperse samples, the optimization should ideally be guided by the predicted fractionating power. Many experimentalists, however, neglect fractionating power and rely on light scattering detection simply to confirm apparent selectivity across the breadth of the eluted peak. The size information returned by the light scattering software is assumed to dispense with any reliance on theory to predict retention, and any departure of theoretical predictions from experimental observations is therefore considered of no importance. Separation depends on efficiency as well as selectivity, however, and efficiency can be a strong function of retention. The fractionation of a polydisperse sample by field-flow fractionation never provides a perfectly separated series of monodisperse fractions at the channel outlet. The outlet stream has some residual polydispersity, and it will be shown in this manuscript that the residual polydispersity is inversely related to the fractionating power. Due to the strong dependence of light scattering intensity and its angular distribution on the size of the scattering species, the outlet polydispersity must be minimized if reliable size data are to be obtained from the light scattering detector signal. It is shown that light scattering detection should be used with careful control of fractionating power to obtain optimized analysis of polydisperse samples. Part I is concerned with isocratic operation of As-FlFFF, and part II with programmed operation.

  4. Drug-eluting medical implants.

    PubMed

    Zilberman, Meital; Kraitzer, Amir; Grinberg, Orly; Elsner, Jonathan J

    2010-01-01

    Drug-eluting medical implants are actually active implants that induce healing effects, in addition to their regular task of support. This effect is achieved by controlled release of active pharmaceutical ingredients (API) into the surrounding tissue. In this chapter we focus on three types of drug-eluting devices: drug-eluting vascular stents, drug-eluting wound dressings and protein-eluting scaffolds for tissue regeneration, thus describing both internal and external implants. Each of these drug-eluting devices also presents an approach for solving the drug release issue. Most drug-eluting vascular stents are loaded with water-insoluble antiproliferative agents, and their diffusion from the device to the surrounding tissue is relatively slow. In contrast, most drug-eluting wound dressings are loaded with highly water-soluble antibacterial agents and the issue of fast release must therefore be addressed. Growth factor release from scaffolds for tissue regeneration offers a new approach of incorporating high-molecular-weight bioactive agents which are very sensitive to process conditions and preserve their activity during the preparation stage. The drug-eluting medical implants are described here in terms of matrix formats and polymers, incorporated drugs and their release profiles from the implants, and implant functioning. Basic elements, such as new composite core/shell fibers and structured films, can be used to build new antibiotic-eluting devices. As presented in this chapter, the effect of the processing parameters on the microstructure and the resulting drug release profiles, mechanical and physical properties, and other relevant properties, must be elucidated in order to achieve the desired properties. Newly developed implants and novel modifications of previously developed approaches have enhanced the tools available for creating clinically important biomedical applications.

  5. Expressions of the fundamental equation of gradient elution and a numerical solution of these equations under any gradient profile.

    PubMed

    Nikitas, P; Pappa-Louisi, A

    2005-09-01

    The original work carried out by Freiling and Drake in gradient liquid chromatography is rewritten in the current language of reversed-phase liquid chromatography. This allows for the rigorous derivation of the fundamental equation for gradient elution and the development of two alternative expressions of this equation, one of which is free from the constraint that the holdup time must be constant. In addition, the above derivation results in a very simple numerical solution of the various equations of gradient elution under any gradient profile. The theory was tested using eight catechol-related solutes in mobile phases modified with methanol, acetonitrile, or 2-propanol. It was found to be a satisfactory prediction of solute gradient retention behavior even if we used a simple linear description for the isocratic elution of these solutes. PMID:16131080

  6. Elution profiles of lanthanides with α-hydroxyisobutyric acid by ion exchange chromatography using fine resin.

    PubMed

    Trikha, Rahul; Sharma, Bal Krishan; Sabharwal, Kanwal Nain; Prabhu, Krishan

    2015-11-01

    Experiments were carried out using a strong acid cation exchange resin with a particle size of 75-150 μm, termed as "fine resin" in hydrogen ion form for the elution of individual lanthanides Sm, Eu, Gd, Tb, and Dy that are produced as fission products in the spent nuclear fuel and generated in the effluent during reprocessing of spent nuclear fuel. Batch experiments were carried out to study the effect of concentration of nitric acid on distribution coefficient. The distribution coefficient values for these individual lanthanides were determined in nitric acid medium in the concentration range of 0.01-4.0 N. Uptake of each individual lanthanide by resin was increased with increased nitric acid concentration from 0.01 to 0.5 N and remained similar from 0.5 to 1.0 N and decreased thereafter up to 4.0 N. Column experiments were also carried out using the same resin to study the parameters like pH of the eluent, flow rate, and resin bed height under isocratic elution conditions for eluting lanthanide elements using α-hydroxyisobutyric acid as eluent. The results of this study have indicated the possibility for the elution of individual lanthanides.

  7. Isocratic liquid chromatographic determination of theophylline, acetaminophen, chloramphenicol, caffeine, anticonvulsants, and barbiturates in serum.

    PubMed

    Meatherall, R; Ford, D

    1988-01-01

    An isocratic reverse-phase high-performance liquid chromatographic system is described for resolving theophylline, acetaminophen, caffeine, chloramphenicol, ethosuximide, primidone, phenobarbital, phenytoin, and carbamazepine within 7 min. A procedure for routinely measuring these drugs in serum is validated and has been extended to include the quantification of N-desmethylmethsuximide, barbital, amobarbital, secobarbital, pentobarbital, mephobarbital, and thiopental. A 250 x 4.6 mm column packed with trimethylsilyl (C-1)-coated 5-microns particles is used. The mobile phase is phosphate buffer (10 mmol/L, pH 6.3):methanol:acetonitrile, 65:17.5:17.5. A common solvent extraction procedure is used for all of these drugs. The extractant is chloroform:isopropanol (95:5), containing three internal standards: 3-isobutyl-l-methylxanthine (IMX), tolybarb, and methsuximide. Theophylline, acetaminophen, caffeine, and chloramphenicol are quantified at 273 nm with IMX as the internal standard. With two exceptions, the rest of the drugs are quantified at 204 nm using tolybarb as the internal standard; ethosuximide is quantified at 204 nm using methsuximide as the internal standard, and thiopental is quantified at 285 nm using IMX as the internal standard.

  8. ELUTION OF URANIUM FROM RESIN

    DOEpatents

    McLEan, D.C.

    1959-03-10

    A method is described for eluting uranium from anion exchange resins so as to decrease vanadium and iron contamination and permit recycle of the major portion of the eluats after recovery of the uranium. Diminution of vanadium and iron contamination of the major portion of the uranium is accomplished by treating the anion exchange resin, which is saturated with uranium complex by adsorption from a sulfuric acid leach liquor from an ore bearing uranium, vanadium and iron, with one column volume of eluant prepared by passing chlorine into ammonium hydroxide until the chloride content is about 1 N and the pH is about 1. The resin is then eluted with 8 to 9 column volumes of 0.9 N ammonium chloride--0.1 N hydrochloric acid solution. The eluants are collected separately and treated with ammonia to precipitate ammonium diuranate which is filtered therefrom. The uranium salt from the first eluant is contaminated with the major portion of ths vanadium and iron and is reworked, while the uranium recovered from the second eluant is relatively free of the undesirable vanadium and irons. The filtrate from the first eluant portion is discarded. The filtrate from the second eluant portion may be recycled after adding hydrochloric acid to increase the chloride ion concentration and adjust the pH to about 1.

  9. Instrument Parameters Controlling Retention Precision in Gradient Elution Reversed-Phase Liquid Chromatography

    PubMed Central

    Beyaz, Ayse; Fan, Wenzhe; Carr, Peter W.; Schellinger, Adam P.

    2014-01-01

    The precision of retention time in RPLC is important for compound identification, for setting peak integration time windows and in fundamental studies of retention. In this work, we studied the effect of temperature (T), initial (ϕ0) and final mobile phase (ϕf)composition, gradient time (tG), and flow rate (F) on the retention time precision under gradient elution conditions for various types of low MW solutes. We determined the retention factor in pure water (k′w) and the solute-dependent solvent strength (S) parameters of Snyder's linear solvent strength theory (LSST) as a function of temperature for three different groups of solutes. The effect of small changes in the chromatographic variables (T, ϕ0, ϕf, tG and F) by use of the LSST gradient retention equation were estimated. Peaks at different positions in the chromatogram have different sensitivities to changes in these instrument parameters. In general, absolute fluctuations in retention time are larger at longer gradient times. Drugs showed less sensitivity to changes in temperature compared to relatively less polar solutes, non-ionogenic solutes. Surprisingly we observed that fluctuations in temperature, mobile phase composition and flow rate had less effect on retention time under gradient conditions as compared to isocratic conditions. Overall temperature and the initial mobile phase composition are the more important variables affecting retention reproducibility in gradient elution chromatography. PMID:25459648

  10. An isocratic ion exchange HPLC method for the simultaneous determination of flucloxacillin and amoxicillin in a pharmaceutical formulation for injection.

    PubMed

    Liu, Hao; Wang, Hongwu; Sunderland, V Bruce

    2005-02-23

    An isocratic ion exchange high performance liquid chromatography method was developed for the simultaneous determination of flucloxacillin and amoxicillin in pharmaceutical formulations for injections. The separation was made by a ZORBAX 300-SCX column using 0.025 M ammonium dihydrogen phosphate (adjusted to pH 2.6 with phosphoric acid)-acetonitrile (95:5) as mobile phase. The validation of the method was performed, and specificity, reproducibility, precision and accuracy were confirmed. The limits of quantification were approximately 0.2 microg/ml for each drug. Due to its simplicity and accuracy the method is particularly suitable for routine pharmaceutical quality control.

  11. Gradient elution in capillary electrochromatography

    SciTech Connect

    Anex, D.; Rakestraw, D.J.; Yan, Chao; Dadoo, R.; Zare, R.N.

    1997-08-01

    In analogy to pressure-driven gradient techniques in high-performance liquid chromatography, a system has been developed for delivering electroosmotically-driven solvent gradients for capillary electrochromatography (CEC). Dynamic gradients with sub-mL/min flow rates are generated by merging two electroosmotic flows that are regulated by computer-controlled voltages. These flows are delivered by two fused-silica capillary arms attached to a T-connector, where they mix and then flow into a capillary column that has been electrokinetically packed with 3-mm reversed-phase particles. The inlet of one capillary arm is placed in a solution reservoir containing one mobile phase and the inlet of the other is placed in a second reservoir containing a second mobile phase. Two independent computer-controlled programmable high-voltage power supplies (0-50 kV)--one providing an increasing ramp and the other providing a decreasing ramp--are used to apply variable high-voltage potentials to the mobile phase reservoirs to regulate the electroosmotic flow in each arm. The ratio of the electroosmotic flow rates between the two arms is changed with time according to the computer-controlled voltages to deliver the required gradient profile to the separation column. Experiments were performed to confirm the composition of the mobile phase during a gradient run and to determine the change of the composition in response to the programmed voltage profile. To demonstrate the performance of electroosmotically-driven gradient elution in CEC, a mixture of 16 polycyclic aromatic hydrocarbons (PAHs) was separated in less than 90 minutes. This gradient technique is expected to be well-suited for generating not only solvent gradients in CEC, but also other types of gradients such as pH- and ionic-strength gradients in capillary electrokinetic separations and analyses.

  12. Evaluation of ion exchange processes in drug-eluting embolization beads by use of an improved flow-through elution method.

    PubMed

    Swaine, Tanya; Tang, Yiqing; Garcia, Pedro; John, Jasmine; Waters, Laura J; Lewis, Andrew L

    2016-10-10

    An improved method for evaluating drug release behaviour of drug-eluting embolization beads (DEBs) was developed utilizing an open-loop flow-through system, in which the beads were packed into an occlusive mass within the system and extracted with a flowing elution medium over time. Glass beads were introduced into the beads mass in order to ensure laminar flow, reduce dead volume and improve reproducibility by compensating for swelling phenomena. The effects of glass bead ratio, elution medium flow rate and ion concentration, DEB size and drug concentration and drug type (doxorubicin and irinotecan) were evaluated using DEB composed of a sulfonate-modified polyvinyl alcohol hydrogel (DC Bead™) as the test article. The rate and amount of drug elution from the packed beads was affected by flow rate, the bead size and initial loading dose. The raw data from the concentration profile analysis provided valuable information to reveal the drug elution behaviour akin to the pharmacokinetic data observed for embolized beads (yielding in vitro Cmax and tmax data) which was complementary to the normal cumulative data obtained. A good correlation with historical reported in vivo data validated the usefulness of the method for predicting in vivo drug elution behaviour.

  13. Evaluation of ion exchange processes in drug-eluting embolization beads by use of an improved flow-through elution method.

    PubMed

    Swaine, Tanya; Tang, Yiqing; Garcia, Pedro; John, Jasmine; Waters, Laura J; Lewis, Andrew L

    2016-10-10

    An improved method for evaluating drug release behaviour of drug-eluting embolization beads (DEBs) was developed utilizing an open-loop flow-through system, in which the beads were packed into an occlusive mass within the system and extracted with a flowing elution medium over time. Glass beads were introduced into the beads mass in order to ensure laminar flow, reduce dead volume and improve reproducibility by compensating for swelling phenomena. The effects of glass bead ratio, elution medium flow rate and ion concentration, DEB size and drug concentration and drug type (doxorubicin and irinotecan) were evaluated using DEB composed of a sulfonate-modified polyvinyl alcohol hydrogel (DC Bead™) as the test article. The rate and amount of drug elution from the packed beads was affected by flow rate, the bead size and initial loading dose. The raw data from the concentration profile analysis provided valuable information to reveal the drug elution behaviour akin to the pharmacokinetic data observed for embolized beads (yielding in vitro Cmax and tmax data) which was complementary to the normal cumulative data obtained. A good correlation with historical reported in vivo data validated the usefulness of the method for predicting in vivo drug elution behaviour. PMID:27523788

  14. Elution of leachable components from composites.

    PubMed

    Ferracane, J L

    1994-07-01

    A significant amount of residual monomer or short chain polymers remain unbound in set composite material. Due to its potential impact on both the biocompatibility and the structural stability of the restoration, many investigators have studied the elution of these unbound molecules into aqueous media. The results of these studies suggest that elution of leachable components from composites is rapid, with the majority being released within a matter of hours. Weight losses of up to 2% of the mass of the composite have been reported under certain conditions. The studies have also shown that the extent and rate of elution of components from composites is dependent upon several factors. The quantity of leachables has been correlated to the degree of cure of the polymer network. The composition and solubility characteristics of the extraction solvent influence the kinetics and mechanism of the elution process. Elution is generally thought to occur via diffusion of molecules through the resin matrix, and is therefore dependent upon the size and chemical characteristics of the leachable species.

  15. Evaluation of electrochemical ion exchange for cesium elution

    SciTech Connect

    Bontha, J.D.; Kurath, D.E.; Surma, J.E.; Buehler, M.F.

    1996-04-01

    Electrochemical elution was investigated as an alternative method to acid elution for the desorption of cesium from loaded ion exchange resins. The approach was found to have several potential advantages over existing technologies, in particular, electrochemical elution eliminates the need for addition of chemicals to elute cesium from the ion exchange resin. Also, since, in the electrochemical elution process the eluting solution is not in direct contact with the ion exchange material, very small volumes of the eluting solution can be used in a complete recycle mode in order to minimize the total volume of the cesium elute. In addition, the cesium is eluted as an alkaline solution that does not require neutralization with caustic to meet the tank farm specifications. Other advantages include easy incorporation of the electrochemical elution process into the present cesium recovery schemes.

  16. Fractionated elution using the TEKCIS technetium-99m generator.

    PubMed

    Vigne, Jonathan; De Mil, Rémy; Peyronnet, Damien; Hecquard, Claudine; Agostini, Denis; Lemonnier, Françoise

    2016-06-01

    The TEKCIS technetium-99m (Tc) generator was designed to allow dry column shipment and automatized conception. A high Tc radioactive concentration is required in a subset of radiopharmacy procedures. Fractionated elution can be a useful tool to meet this requirement, especially when current elution is close to the generator expiration date. The aim of our study was to assess TEKCIS generator elution kinetics and to determine the optimal fractionated elution time to fit with procedures requiring the highest Tc radioactive concentration in clinical use. After duplicate elution at several predetermined elution times, the volume and activity of each eluate were measured. Two optimal time points were selected to perform fractionated elution and repeatability (n=34 and 33) assessed on TEKCIS generators calibrated at 6 or 8 GBq. The complete eluate volume (5 ml) was collected after 60 s of elution. A logarithmic equation was established between eluate volume (v, ml) from elapsed elution time (t, s): v=1.8335ln(t)-2.5965. Using the reciprocal equation, elution times required to obtain some commonly eluted volumes were calculated. Fractionated elutions during 15 and 20 s were selected and an average elution volume from 2.74 to 3.27 ml was collected, with an average elution yield of approximately 90 and 100%, respectively. Our work provides a simple and reliable methodology for the use of fractionated elution with the new TEKCIS generator.

  17. Accurate retention time determination of co-eluting proteins in analytical chromatography by means of spectral data.

    PubMed

    Dismer, Florian; Hansen, Sigrid; Oelmeier, Stefan Alexander; Hubbuch, Jürgen

    2013-03-01

    Chromatography is the method of choice for the separation of proteins, at both analytical and preparative scale. Orthogonal purification strategies for industrial use can easily be implemented by combining different modes of adsorption. Nevertheless, with flexibility comes the freedom of choice and optimal conditions for consecutive steps need to be identified in a robust and reproducible fashion. One way to address this issue is the use of mathematical models that allow for an in silico process optimization. Although this has been shown to work, model parameter estimation for complex feedstocks becomes the bottleneck in process development. An integral part of parameter assessment is the accurate measurement of retention times in a series of isocratic or gradient elution experiments. As high-resolution analytics that can differentiate between proteins are often not readily available, pure protein is mandatory for parameter determination. In this work, we present an approach that has the potential to solve this problem. Based on the uniqueness of UV absorption spectra of proteins, we were able to accurately measure retention times in systems of up to four co-eluting compounds. The presented approach is calibration-free, meaning that prior knowledge of pure component absorption spectra is not required. Actually, pure protein spectra can be determined from co-eluting proteins as part of the methodology. The approach was tested for size-exclusion chromatograms of 38 mixtures of co-eluting proteins. Retention times were determined with an average error of 0.6 s (1.6% of average peak width), approximated and measured pure component spectra showed an average coefficient of correlation of 0.992.

  18. Highly porous drug-eluting structures

    PubMed Central

    Elsner, Jonathan J.; Kraitzer, Amir; Grinberg, Orly; Zilberman, Meital

    2012-01-01

    For many biomedical applications, there is need for porous implant materials. The current article focuses on a method for preparation of drug-eluting porous structures for various biomedical applications, based on freeze drying of inverted emulsions. This fabrication process enables the incorporation of any drug, to obtain an “active implant” that releases drugs to the surrounding tissue in a controlled desired manner. Examples for porous implants based on this technique are antibiotic-eluting mesh/matrix structures used for wound healing applications, antiproliferative drug-eluting composite fibers for stent applications and local cancer treatment, and protein-eluting films for tissue regeneration applications. In the current review we focus on these systems. We show that the release profiles of both types of drugs, water-soluble and water-insoluble, are affected by the emulsion's formulation parameters. The former's release profile is affected mainly through the emulsion stability and the resulting porous microstructure, whereas the latter's release mechanism occurs via water uptake and degradation of the host polymer. Hence, appropriate selection of the formulation parameters enables to obtain desired controllable release profile of any bioactive agent, water-soluble or water-insoluble, and also fit its physical properties to the application. PMID:23507890

  19. Cost-Effectiveness Analysis of Infrapopliteal Drug-Eluting Stents

    SciTech Connect

    Katsanos, Konstantinos Karnabatidis, Dimitris; Diamantopoulos, Athanasios; Spiliopoulos, Stavros; Siablis, Dimitris

    2013-02-15

    IntroductionThere are no cost-utility data about below-the-knee placement of drug-eluting stents. The authors determined the cost-effectiveness of infrapopliteal drug-eluting stents for critical limb ischemia (CLI) treatment. The event-free individual survival outcomes defined by the absence of any major events, including death, major amputation, and target limb repeat procedures, were reconstructed on the basis of two published infrapopliteal series. The first included spot Bail-out use of Sirolimus-eluting stents versus bare metal stents after suboptimal balloon angioplasty (Bail-out SES).The second was full-lesion Primary Everolimus-eluting stenting versus plain balloon angioplasty and bail-out bare metal stenting as necessary (primary EES). The number-needed-to-treat (NNT) to avoid one major event and incremental cost-effectiveness ratios (ICERs) were calculated for a 3-year postprocedural period for both strategies. Overall event-free survival was significantly improved in both strategies (hazard ratio (HR) [confidence interval (CI)]: 0.68 [0.41-1.12] in Bail-out SES and HR [CI]: 0.53 [0.29-0.99] in Primary EES). Event-free survival gain per patient was 0.89 (range, 0.11-3.0) years in Bail-out SES with an NNT of 4.6 (CI: 2.5-25.6) and a corresponding ICER of 6,518 Euro-Sign (range 1,685-10,112 Euro-Sign ). Survival gain was 0.91 (range 0.25-3.0) years in Primary EES with an NNT of 2.7 (CI: 1.7-5.8) and an ICER of 11,581 Euro-Sign (range, 4,945-21,428 Euro-Sign ) per event-free life-year gained. Two-way sensitivity analysis showed that stented lesion length >10 cm and/or DES list price >1000 Euro-Sign were associated with the least economically favorable scenario in both strategies. Both strategies of bail-out SES and primary EES placement in the infrapopliteal arteries for CLI treatment exhibit single-digit NNT and relatively low corresponding ICERs.

  20. ELUTION OF URANIUM VALUES FROM ION EXCHANGE RESINS

    DOEpatents

    Kennedy, R.H.

    1959-11-24

    A process is described for eluting complex uranium ions absorbed on ion exchange resins. The resin is subjected to the action of an aqueous eluting solution contuining sulfuric acid and an alkali metal, ammonium, or magnesium chloride or nitrate, the elution being carried out until the desired amount of the uranium is removed from the resin.

  1. Recent Advances in Drug Eluting Stents

    PubMed Central

    Puranik, Amey S.; Dawson, Eileen R.; Peppas, Nicholas A.

    2013-01-01

    One of the most common medical interventions to reopen an occluded vessel is the implantation of a coronary stent. While this method of treatment is effective initially, restenosis, or the re-narrowing of the artery frequently occurs largely due to neointimal hyperplasia of smooth muscle cells. Drug eluting stents were developed in order to provide local, site-specific, controlled release of drugs that can inhibit neointima formation. By implementing a controlled release delivery system it may be possible to control the time release of the pharmacological factors and thus be able to bypass some of the critical events associated with stent hyperplasia and prevent the need for subsequent intervention. However, since the advent of first-generation drug eluting stents, long-term adverse effects have raised concerns regarding their safety. These limitations in safety and efficacy have triggered considerable research in developing biodegradable stents and more potent drug delivery systems. In this review, we shed light on the current state-of-the-art in drug eluting stents, problems related to them and highlight some of the ongoing research in this area. PMID:23117022

  2. The Supralimus sirolimus-eluting stent.

    PubMed

    Lemos, Pedro A; Bienert, Igor

    2013-05-01

    The use of biodegradable polymeric coatings has emerged as a potential bioengineering target to improve the vascular compatibility of coronary drug-eluting stents (DESs). This review summarizes the main features and scientific facts about the Supralimus sirolimus-eluting stent (Sahajanand Medical Technologies Ltd, Surat, India), which is a biodegradable polymer-based, sirolimus-eluting metallic stent that was recently introduced for routine use in Europe. The novel stent is built on a stainless steel platform, coated with a blend of biodegradable polymers (poly-l-lactide, poly-dl-lactide-co-glycolide and polyvinyl pyrrolidone; coating thickness is 4-5 µm). The active agent is the antiproliferative sirolimus in a dose load of 1.4 µg/mm(2), which is released within 48 days. The Supralimus stent was initially evaluated in the single-arm SERIES-I study, which showed binary angiographic restenosis rates of 0% (in-stent) and 1.7% (in-segment) and an in-stent late lumen loss of 0.09 ± 0.28 mm. The multicenter randomized PAINT trial compared two DESs with identical metallic platforms and biodegradable polymer carriers, but different agents (Infinnium [Sahajanand Medical Technologies Pvt Ltd] paclitaxel-eluting stent or Supralimus sirolimus-eluting stent) against bare stents. After 3 years, the pooled DES population had similar rates of cardiac death or myocardial infarction (9 vs 7.1%; p = 0.6), but a lower risk of repeat interventions (10 vs 29.9%; p < 0.01) than controls with bare stents. The incidence of definite or probable stent thrombosis in the pooled DES group was 2.3% (1st year: 1.8%; 2nd year: 0.4% and 3rd year: 0%). These results demonstrate that the novel Supralimus stents are effective in reducing reintervention, while potentially improving the safety profile by decreasing the risk of late-term thrombosis, even though further studies would be necessary to confirm these findings.

  3. The Supralimus sirolimus-eluting stent.

    PubMed

    Lemos, Pedro A; Bienert, Igor

    2013-05-01

    The use of biodegradable polymeric coatings has emerged as a potential bioengineering target to improve the vascular compatibility of coronary drug-eluting stents (DESs). This review summarizes the main features and scientific facts about the Supralimus sirolimus-eluting stent (Sahajanand Medical Technologies Ltd, Surat, India), which is a biodegradable polymer-based, sirolimus-eluting metallic stent that was recently introduced for routine use in Europe. The novel stent is built on a stainless steel platform, coated with a blend of biodegradable polymers (poly-l-lactide, poly-dl-lactide-co-glycolide and polyvinyl pyrrolidone; coating thickness is 4-5 µm). The active agent is the antiproliferative sirolimus in a dose load of 1.4 µg/mm(2), which is released within 48 days. The Supralimus stent was initially evaluated in the single-arm SERIES-I study, which showed binary angiographic restenosis rates of 0% (in-stent) and 1.7% (in-segment) and an in-stent late lumen loss of 0.09 ± 0.28 mm. The multicenter randomized PAINT trial compared two DESs with identical metallic platforms and biodegradable polymer carriers, but different agents (Infinnium [Sahajanand Medical Technologies Pvt Ltd] paclitaxel-eluting stent or Supralimus sirolimus-eluting stent) against bare stents. After 3 years, the pooled DES population had similar rates of cardiac death or myocardial infarction (9 vs 7.1%; p = 0.6), but a lower risk of repeat interventions (10 vs 29.9%; p < 0.01) than controls with bare stents. The incidence of definite or probable stent thrombosis in the pooled DES group was 2.3% (1st year: 1.8%; 2nd year: 0.4% and 3rd year: 0%). These results demonstrate that the novel Supralimus stents are effective in reducing reintervention, while potentially improving the safety profile by decreasing the risk of late-term thrombosis, even though further studies would be necessary to confirm these findings. PMID:23597097

  4. Purification of glycolytic enzymes by using affinity-elution chromatography.

    PubMed Central

    Scopes, R K

    1977-01-01

    1. A systematic procedure for the purification of enzymes by affinity-elution chromatography is described. Enzymes are adsorbed on a cation-exchanger, and eluted with ligands specific for the enzyme concerned. 2. All of the glycolytic and some related enzymes present in rabbit muscle can be purified by the affinity-elution technique. The pH range for adsorption and elution of each enzyme was found, and the effects of minor variations of conditions are described. 3. A description of experimental conditions suitable for affinity elution of each enzyme is given, together with special features relevant to each individual enzyme. 4. Theoretical considerations of affinity elution chromatography are discussed, including its limitations, advantages and disadvantages compared with affinity-adsorption chromatography. Possible developments are suggested to cover enzymes which because of their adsorption characteristics are not at present amenable to affinity-elution procedures. PMID:192194

  5. Endovascular Gene Delivery from a Stent Platform: Gene- Eluting Stents

    PubMed Central

    Fishbein, Ilia; Chorny, Michael; Adamo, Richard F; Forbes, Scott P; Corrales, Ricardo A; Alferiev, Ivan S; Levy, Robert J

    2015-01-01

    A synergistic impact of research in the fields of post-angioplasty restenosis, drug-eluting stents and vascular gene therapy over the past 15 years has shaped the concept of gene-eluting stents. Gene-eluting stents hold promise of overcoming some biological and technical problems inherent to drug-eluting stent technology. As the field of gene-eluting stents matures it becomes evident that all three main design modules of a gene-eluting stent: a therapeutic transgene, a vector and a delivery system are equally important for accomplishing sustained inhibition of neointimal formation in arteries treated with gene delivery stents. This review summarizes prior work on stent-based gene delivery and discusses the main optimization strategies required to move the field of gene-eluting stents to clinical translation. PMID:26225356

  6. Prediction of Neutral Salt Elution Profiles for Affinity Chromatography

    NASA Astrophysics Data System (ADS)

    Robinson, Jack B.; Strottmann, James M.; Stellwagen, Earle

    1981-04-01

    Neutral salts exhibit very marked differences as eluants of proteins from affinity columns. We observe: (i) that the relative potencies of neutral salts as eluants are independent of the protein or the affinity ligand in the systems studied, (ii) that the absolute salt concentration necessary to elute any given protein bound to the affinity matrix is proportional to the algebraic sum of a set of elution coefficients defined herein for the separate ions present in the solution, and (iii) that the proportionality between elution potency and elution coefficient is a function of the affinity of the protein for the immobilized ligand. Given the concentration of one neutral salt required for elution of a protein of interest from an affinity column, the elution capability of any neutral salt at any temperature can be quantitatively predicted for that protein. Accordingly, application and elution protocols for affinity chromatography can be designed to optimize the yield and fold purification of proteins.

  7. Modelling Simple Experimental Platform for In Vitro Study of Drug Elution from Drug Eluting Stents (DES)

    NASA Astrophysics Data System (ADS)

    Kalachev, L. V.

    2016-06-01

    We present a simple model of experimental setup for in vitro study of drug release from drug eluting stents and drug propagation in artificial tissue samples representing blood vessels. The model is further reduced using the assumption on vastly different characteristic diffusion times in the stent coating and in the artificial tissue. The model is used to derive a relationship between the times at which the measurements have to be taken for two experimental platforms, with corresponding artificial tissue samples made of different materials with different drug diffusion coefficients, to properly compare the drug release characteristics of drug eluting stents.

  8. Extended elution of phospholipid from silicone hydrogel contact lenses.

    PubMed

    Pitt, William G; Zhao, Yibei; Jack, Daniel R; Perez, Krystian X; Jones, Peter W; Marelli, Ryan; Nelson, Jared L; Pruitt, John D

    2015-01-01

    Characterization of phospholipid release from an experimental reusable wear silicone hydrogel contact lens was performed to assess the possible use of these lenses for phospholipid delivery to increase eye comfort to patients who prefer reusable wear lenses. Contact lenses were loaded with 200 μg of radio-labeled 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) from a solution of n-propanol. To simulate 30 days of diurnal use with overnight cleaning, these lenses were eluted for 16 h at 35 °C into artificial tear fluid (ATF), and then eluted at room temperature (~22 °C) for 8 h in one of three commercial contact lens cleaning systems. This was repeated for 30 days. The elution of DMPC into ATF was greater on the first day, followed by a fairly constant amount of elution each day thereafter. The type of cleaning system had a statistically significant effect on the elution rate during daily exposure to ATF. The rate of elution into cleaning solutions did not show any enhanced elution on the first day; there was a fairly constant elution rate. Again, the type of cleaning system significantly influenced the elution rate into the nightly cleaner.

  9. Mixed-mode ion-exchangers and their comparative chromatographic characterization in reversed-phase and hydrophilic interaction chromatography elution modes.

    PubMed

    Lämmerhofer, Michael; Richter, Martin; Wu, Junyan; Nogueira, Raquel; Bicker, Wolfgang; Lindner, Wolfgang

    2008-08-01

    A set of particulate silica-supported mixed-mode RP/weak anion-exchangers (RP/WAX) (obtained by bonding of N-undecenoylated 3-aminoquinuclidine, 3-aminotropane and 2-dimethylaminoethylamine as well as of N-butenoyl-(2S,4S,5R)-2-aminomethyl-5-[(2-octylthio)ethyl]-quinuclidine to thiol-modified silica) were chromatographically characterized in comparison to selected commercially available columns using two distinct isocratic elution modes, viz. an aqueous-rich RP-type elution mode (with 40% ACN and 60% buffer) as well as an organic solvent-rich hydrophilic interaction chromatography (HILIC)-type elution mode (95 and 90% ACN). The mixed-mode RP/WAX phases showed multimodal applicability, unlike a polar embedded RP material (Synergi Fusion RP), amino phases (Luna NH(2), BioBasic AX) or typical HILIC packings (ZIC-HILIC, TSKGel Amide-80). Principal component analysis (PCA) of the RP test data confirmed that the in-house developed RP/WAX columns as well as the Acclaim Mixed-Mode WAX-1 phase resemble each other in their chromatographic characteristics having slightly lower hydrophobic selectivity (alpha(CH2) of 1.5) than the tested Synergi Fusion RP (alpha(CH2) approximately 1.8). In contrast, a decrease in mixed-mode character due to lowered ion-exchange capacity and concomitantly increased RP-like behavior could be identified for other mixed-mode phases in the order of Obelisc R > Primesep B2 > Uptisphere MM3. PCA on HILIC data revealed that the RP/WAX phases behave dissimilar to TSKGel Amide-80, ZIC-HILIC and polysulfoethyl A under the chosen elution conditions. Hence, they may be regarded as complementary to these commercial stationary phases with applicability profiles for hydrophilic but also hydrophobic solutes. PMID:18693304

  10. [Recent developments of drug eluting stent coatings].

    PubMed

    Chen, Wen-ping; Zhan, Hong-bing

    2011-11-01

    Drug eluting stents (DESs) have revolutionized the interventional cardiology over the past decade since the first DES became commercially available in Europe in 2002. Compared to bare metal stents that are deployed to keep the vessel open by mechanical force, DESs have an additional function of reducing restenosis by the action of the drug on the target site. Coatings on the stent surface which ensure the maximum delivery of therapeutic agents to the target site with minimal systematic toxicity, also play an important role in adjusting the drug release profile. Coating material and technology not only affect the surface biocompatibility and the integrity maintenance during the implanting process, but also decide the way of drug delivering and transmitting from the coating. This paper reviews the basic principles of DES coating design, the categories of DES coatings, the commonly used clinical DES coatings and their efficiency in reducing restenosis, and finally provides the future perspectives for DES coatings. PMID:22260019

  11. Native Elution of Yeast Protein Complexes Obtained by Affinity Capture.

    PubMed

    LaCava, John; Fernandez-Martinez, Javier; Rout, Michael P

    2016-01-01

    This protocol describes two options for the native (nondenaturing) elution of protein complexes obtained by affinity capture. The first approach involves the elution of complexes purified through a tag that includes a human rhinovirus 3C protease (PreScission protease) cleavage site sequence between the protein of interest and the tag. Incubation with the protease cleaves immobilized complexes from the affinity medium. The second approach involves the release of protein A-tagged protein complexes using a competitive elution reagent called PEGylOx. The degree of purity of the native assemblies eluted is sample dependent and strongly influenced by the affinity capture. It should be noted that the efficiency of native elution is commonly lower than that of elution by a denaturing agent (e.g., SDS) and the release of the complex will be limited by the activity of the protease or the inhibition constant (Ki) of the competitive release agent. However, an advantage of native release is that some nonspecifically bound materials tend to stay adsorbed to the affinity medium, providing an eluted fraction of higher purity. Finally, keep in mind that the presence of the protease or elution peptide could potentially affect downstream applications; thus, their removal should be considered. PMID:27371597

  12. Simultaneous determination of eight biologically active thiol compounds using gradient elution-liquid chromatography with Coul-Array detection.

    PubMed

    Petrlova, Jitka; Mikelova, Radka; Stejskal, Karel; Kleckerova, Andrea; Zitka, Ondrej; Petrek, Jiri; Havel, Ladislav; Zehnalek, Josef; Vojtech, Adam; Trnkova, Libuse; Kizek, Rene

    2006-05-01

    The most active form of sulfur in biomolecules is the thiol group, present in a number of biologically active compounds. Here we present a comprehensive study of thiol analysis using flow injection analysis/HPLC with electrochemical detection. The effect of different potentials of working electrodes, of organic solvent contents in the mobile phase, and of isocratic and gradient elution on simultaneous determination of thiol compounds (cysteine, cystine, N-acetylcysteine, homocysteine, reduced and oxidised glutathione, desglycinephytochelatin, and phytochelatins) are described and discussed. These thiol compounds were well separated and detected under optimised HPLC-electrochemical detection conditions (mobile phase: 80 mM trifluoroacetic acid and methanol with a gradient profile starting at 97:3 (TFA:methanol), kept constant for the first 8 min, then decreasing to 85:15 during one minute, kept constant for 8 min, and finally increasing linearly up to 97:3 from 17 to 18 min; the flow rate was 0.8 mL/min, column and detector temperature 25 degrees C, and the electrode potential 900 mV). We were able to determine tens of femtomoles (3 S/N) of the thiols per injection (5 microL), except for phytochelatin5 whose detection limit was 2.1 pmole. This technique was consequently used for simultaneous determination of compounds of interest in biological samples (maize tissue and human blood serum). PMID:16830732

  13. Determination of six kavalactones in dietary supplements and selected functional foods containing Piper methysticum by isocratic liquid chromatography with internal standard.

    PubMed

    Hu, Lihong; Jhoo, Jin-Woo; Ang, Catharina Y W; Dinovi, Michael; Mattia, Antonia

    2005-01-01

    Kava (Piper methysticum) dietary products have been sold worldwide for treatment of nervous anxiety, tension, and restlessness. Recent reports showed potential association of kava usage and liver injuries. This study was conducted to develop simple and reliable methodologies for the extraction and determination of 6 major kavalactones: (+)-methysticin, (+)-dihydromethysticin, (+)-kavain, (+)-dihydrokavain, yangonin, and desmethoxyyangonin. Ultrasonic extraction techniques and isocratic reversed-phase liquid chromatography (LC) were optimized for different types of samples, including capsules containing kava root extract or root powder, raw root material, tea bags, and snack bar. A suitable internal standard, 5,7-dihydroxyflavone, was used for LC calibration. Kavalactones were completely separated in 30 min using a Luna C18-2 column at 60 degrees C with an isocratic mobile phase consisting of 2-propanol-acetonitrile-water-acetic acid (16 + 16 + 68 + 0.1, v/v/v/v). Within-laboratory, intraday, and interday method variation (% relative standard deviation) for most samples extracted by methanol or methanol-water mixture were <5%. Lower levels of kavalactone contents and higher variations were observed for tea bags from water extraction or infusion as compared to methanol extraction. Labeling information of tea bags based on methanol extraction could be misleading to consumers. Analytical recoveries of snack bar fortified at 10 and 20 microg/g were >84% with RSD values <8%. Methods developed in this study offer a simple and reproducible means for analysis of kavalactones in various matrixes of dietary products. PMID:15759721

  14. [Elution of urinary proteins preserved on nitrocellulose membrane with heating].

    PubMed

    Qin, Weiwei; Gao, Youhe

    2015-09-01

    The preservation of urinary proteins on a membrane plays a vital role in biomarker research, and the efficient elution of proteins preserved on nitrocellulose membrane (NC membrane) determines the application of this method. During the heating elution procedure, we raised the temperature to reduce the intense vortexing time, and kept gentle rotating while precipitation to prevent nitrocellulose reformation. We also used SDS-PAGE and LC-MS/MS to analyze the urinary proteins prepared by heating elution procedure, intense vortexing elution procedure and acetone precipitation method. There was no degradation of proteins prepared by heating elution procedure. Compared with proteins prepared by heating elution method and acetone precipitation method, the overlapping rates of the proteins was almost the same (92.6% versus 96.8%) and the ratios of CV values (< 20%) of the proteins were both high (85.2% and 94.4%). The heating elution procedure achieved good technical reproducibility, and was much simpler and more efficient than the previous one. It can facilitate the application of the preservation of urinary proteins on membrane.

  15. Comparisons of Aluminum and Silica Elution from Various Glass Vials.

    PubMed

    Ogawa, Toru; Miyajima, Makoto; Nishimoto, Norihiro; Minami, Hidemi; Terada, Katsuhide

    2016-01-01

    To understand the risk of particle formation in glass vials, we investigated the correlation between vial surface condition and alminum (Al) or silicon (Si) elution using various suppliers' vials with or without surface treatment. The elution of Si, which can also be an indicator of Al elution, consists of two phases; the first phase is influenced by roughness of the glass surface at the time of filling, and the second phase is dependent on the fundamental elution rate from the glass tube. When vials were filled with citrate buffer at pH 7, vials with varied surface conditions showed the most obvious differences in Al and Si elution. Sulfur-treated vials showed slightly lower Al and Si elution than the non-treated vials. It is considered that this effect of the sulfur treatment on elution is due to the surface being smoothed during heat treatment after the washing process. Different from the sulfur treatment, silicon dioxide (SiO2)-coated vials hardly showed any Al elution as long as the surface was fully coated with the SiO2 layer. It was found that the protective effect of the SiO2 layer against Al elution is more effective in a vial filled with a solution having a lower pH, due to the lower Si dissolving rate occurring at a lower pH. As shown above, pre-measuring the Si and Al present in a citrate buffer at pH 7 placed within a glass container can be a useful tool for selecting the appropriate container for liquid drugs. PMID:26656229

  16. Isocratic non-aqueous reversed-phase high-performance liquid chromatographic separation of capsanthin and capsorubin in red peppers (Capsicum annuum L.), paprika and oleoresin.

    PubMed

    Weissenberg, M; Schaeffler, I; Menagem, E; Barzilai, M; Levy, A

    1997-01-01

    A simple, rapid high-performance liquid chromatography method has been devised in order to separate and quantify the xanthophylls capsorubin and capasanthin present in red pepper (Capsicum annuum L.) fruits and preparations made from them (paprika and oleoresin). A reversed-phase isocratic non-aqueous system allows the separation of xanthophylls within a few minutes, with detection at 450 nm, using methyl red as internal standard to locate the various carotenoids and xanthophylls found in plant extracts. The selection of extraction solvents, mild saponification conditions, and chromatographic features is evaluated and discussed. The method is proposed for rapid screening of large plant populations, plant selection, as well as for paprika products and oleoresin, and also for nutrition and quality control studies.

  17. Purification of the seven tetranortriterpenoids in neem (Azadirachta indica) seed by counter-current chromatography sequentially followed by isocratic preparative reversed-phase high-performance liquid chromatography.

    PubMed

    Silva, Júlio César T; Jham, Gulab N; Oliveira, Rosângela D'arc L; Brown, Leslie

    2007-06-01

    Counter-current chromatography (CCC) sequentially followed by isocratic preparative reversed-phase high-performance liquid chromatography was used to isolate the seven bio-actives (azadirachtin A, azadirachtin B, azadirachtin H, desacetylnimbin, desacetylsalannin, nimbin and salannin) from the seed concentrate (NSC) of the neem tree (Azadirachta indica A. Juss). Reproducible, narrow polarity range, high purity fractions were obtained from repeated injections of the NSC (700 mg loadings/injection), on to a relatively small volume CCC coil (116 mL). The CCC biphasic solvent system chosen was hexane:butanol:methanol:water (1:0.9:1:0.9, v/v). A mass balance of injected material showed that 95+% were recovered. PMID:17428489

  18. Development and validation of a simple and isocratic reversed-phase HPLC method for the determination of rilpivirine from tablets, nanoparticles and HeLa cell lysates

    PubMed Central

    Date, Abhijit A.; Shibata, Annemarie; Bruck, Patrick; Destache, Christopher J.

    2015-01-01

    In the present investigation, a simple and isocratic HPLC-UV method was developed and validated for determination of rilpivirine (RPV) from dosage forms (tablets and nanoparticles) and biological matrices like HeLa cell lysates. The separation and analysis of RPV was carried out under isocratic conditions using (a) a Gemini reversed-phase C18 column (5 μm; 4.6 × 150 mm) maintained at 35°C, (b) a mobile phase consisting of a mixture of acetonitrile and 25 mM potassium dihydrogen phosphate (in the ratio 50:50 v/v) at a flow rate of 0.6 mL/min and (c) atazanavir as an internal standard. The total run time was 17 min and the analysis of RPV and internal standard was carried out at 290 nm. The method was found to be linear (r2 value > 0.998), specific, accurate and precise over the concentration range of 0.025–2 μg/mL. The lower limit of quantification was 0.025 μg/mL, the limit of detection was 0.008 μg/mL and the recovery of RPV was >90%. The stability of the RPV analytical method was confirmed at various conditions such as room temperature (24 h), −20°C (7 days), three freeze–thaw cycles and storage in an autosampler (4°C for 48 h). The method was successfully applied for the determination of RPV from conventional dosage forms like tablets, from polymeric nanoparticles and from biological matrices like HeLa cell lysates. PMID:25298145

  19. Towards porous polymer monoliths for the efficient, retention-independent performance in the isocratic separation of small molecules by means of nano-liquid chromatography.

    PubMed

    Nischang, Ivo; Teasdale, Ian; Brüggemann, Oliver

    2010-11-26

    We have investigated the free-radical copolymerization dynamics of styrene and divinylbenzene in the presence of micro- and macro-porogenic diluents in 100 μm I.D. sized molds under conditions of slow thermal initiation leading to (macro)porous poly(styrene-co-divinylbenzene) monolithic scaffolds. These specifically designed experiments allowed the quantitative determination of monomer specific conversion against polymerization time to derive the porous polymer scaffold composition at each desirable copolymerization stage after phase separation. This was carried out over a time scale of 3h up to 48 h polymerization time, enabling the efficient and repeatable termination of the polymerization reactions. In parallel, the porous and hydrodynamic properties of the derived monolithic columns were thoroughly studied in isocratic nano-LC mode for the reversed-phase separation of a homologous series of small retained molecules. At the optimized initiator concentration, polymerization temperature and time, the macroporous poly(styrene-co-divinylbenzene) monoliths show a permanent mesoporous pore space, which was readily observable by electron microscopy and indicated by nitrogen adsorption experiments. Under these conditions, we consistently find a polymer scaffold composition which suggests a high degree of cross-linking and thus minimum amount of gel porosity. These columns reveal a retention-insensitive plate height in the separation of small retained molecules which only slightly decreases at increased linear mobile phase velocity. As the polymerization progresses, a build-up of less-densely cross-linked material occurs, which is directly reflected in the observed consistent increase in retention and plate heights. This leads to a significant deterioration in overall isocratic separation performance. The decrease in performance is ascribed in particular to the increased mass transfer resistance governing the monoliths' performance over the whole linear chromatographic

  20. Multiplexed electrokinetic sample fractionation, preconcentration and elution for proteomics.

    PubMed

    Hua, Yujuan; Jemere, Abebaw B; Dragoljic, Jelena; Harrison, D Jed

    2013-07-01

    Both 6 and 8-channel integrated microfluidic sample pretreatment devices capable of performing "in space" sample fractionation, collection, preconcentration and elution of captured analytes via sheath flow assisted electrokinetic pumping are described. Coatings and monolithic polymer beds were developed for the glass devices to provide cationic surface charge and anodal electroosmotic flow for delivery to an electrospray emitter tip. A mixed cationic ([2-(methacryloyloxy)ethyl] trimethylammonium chloride) (META) and hydrophobic butyl methacrylate-based monolithic porous polymer, photopolymerized in the 6- or 8-fractionation channels, was used to capture and preconcentrate samples. A 0.45 wt% META loaded bed generated comparable anodic electroosmotic flow to the cationic polymer PolyE-323 coated channel segments in the device. The balanced electroosmotic flow allowed stable electrokinetic sheath flow to prevent cross contamination of separated protein fractions, while reducing protein/peptide adsorption on the channel walls. Sequential elution of analytes trapped in the SPE beds revealed that the monolithic columns could be efficiently used to provide sheath flow during elution of analytes, as demonstrated for neutral carboxy SNARF (residual signal, 0.08% RSD, n = 40) and charged fluorescein (residual signal, 2.5% n = 40). Elution from monolithic columns showed reproducible performance with peak area reproducibility of ~8% (n = 6 columns) in a single sequential elution and the run-to-run reproducibility was 2.4-6.7% RSD (n = 4) for elution from the same bed. The demonstrated ability of this device design and operation to elute from multiple fractionation beds into a single exit channel for sample analysis by fluorescence or electrospray mass spectrometry is a crucial component of an integrated fractionation and assay system for proteomics. PMID:23712291

  1. Fluid mechanics of DNA double-strand filter elution.

    PubMed Central

    Rudinger, George; Blazek, Ed Robert

    2002-01-01

    Measurement of infrequent DNA double-strand breaks (DSB) in mammalian cells is essential for the understanding of cell damage by ionizing radiation and many DNA-reactive drugs. One of the most important assays for measuring DSB in cellular DNA is filter elution. This study is an attempt to determine whether standard concepts of fluid mechanics can yield a self-consistent model of this process. Major assumptions of the analysis are reptation through a channel formed by surrounding strands, with only strand ends captured by filter pores. Both viscosity and entanglement with surrounding strands are considered to determine the resistance to this motion. One important result is that the average elution time of a strand depends not only on its length, but also on the size distribution of the surrounding strands. This model is consistent with experimental observations, such as the dependence of elution kinetics upon radiation dose, but independence from the size of the DNA sample up to a critical filter loading, and possible overlap of elution times for strands of different length. It indicates how the dependence of elution time on the flow rate could reveal the relative importance of viscous and entanglement resistance, and also predicts the consequences of using different filters. PMID:11751292

  2. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute

    PubMed Central

    Stravinskas, M.; Horstmann, P.; Ferguson, J.; Hettwer, W.; Tarasevicius, S.; Petersen, M. M.; McNally, M. A.; Lidgren, L.

    2016-01-01

    Objectives Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing. The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets. DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory. Materials and Methods We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis. Results The release pattern in vitro was comparable with the obtained release in the patient studies. No recurrence was detected in the osteomyelitis group at latest follow-up (minimum 1.5 years). Conclusions This new biphasic bone substitute containing antibiotics provides safe prevention of bone infections in a range of clinical situations. The in vitro test method predicts the in vivo performance and makes it a reliable tool in the development of future antibiotic-eluting bone-regenerating materials. Cite this article: M. Stravinskas, P. Horstmann, J. Ferguson, W. Hettwer, M. Nilsson, S. Tarasevicius, M. M. Petersen, M. A. McNally, L. Lidgren. Pharmacokinetics of gentamicin eluted from a regenerating

  3. The simultaneous determination of active ingredients in cough-cold mixtures by isocratic reversed-phase ion-pair high-performance liquid chromatography.

    PubMed

    Lau, O W; Chan, K; Lau, Y K; Wong, W C

    1989-01-01

    A simple, rapid and accurate method for the simultaneous determination of active ingredients in cough-cold mixtures using isocratic reversed-phase ion-pair high-performance liquid chromatography has been developed. It involves the use of an octadecylsilane column as the stationary phase with methanol, water, tetrahydrofuran, phosphoric acid mixtures as mobile phase including sodium dioctylsulphosuccinate as the ion-pair agent. The pH of the mobile phase was adjusted to 4.6 by means of phosphoric acid and ammonium hydroxide solutions. The proposed method involves the simple dilution of the samples with the mobile phase and the addition of metoclopramide hydrochloride as the internal standard. The active ingredients under investigation were chlorpheniramine, codeine, diphenhydramine, ephedrine, ethylmorphine, phenylephrine, phenylpropanolamine and pholcodine, which exist as various combinations in cough-cold mixtures. The optimum composition of the mobile phase and the optimum flow rate were determined and are reported. The method was applied to the determination of active ingredients in seven commercially available cough-cold mixtures. PMID:2577452

  4. The simultaneous determination of active ingredients in cough-cold mixtures by isocratic reversed-phase ion-pair high-performance liquid chromatography.

    PubMed

    Lau, O W; Chan, K; Lau, Y K; Wong, W C

    1989-01-01

    A simple, rapid and accurate method for the simultaneous determination of active ingredients in cough-cold mixtures using isocratic reversed-phase ion-pair high-performance liquid chromatography has been developed. It involves the use of an octadecylsilane column as the stationary phase with methanol, water, tetrahydrofuran, phosphoric acid mixtures as mobile phase including sodium dioctylsulphosuccinate as the ion-pair agent. The pH of the mobile phase was adjusted to 4.6 by means of phosphoric acid and ammonium hydroxide solutions. The proposed method involves the simple dilution of the samples with the mobile phase and the addition of metoclopramide hydrochloride as the internal standard. The active ingredients under investigation were chlorpheniramine, codeine, diphenhydramine, ephedrine, ethylmorphine, phenylephrine, phenylpropanolamine and pholcodine, which exist as various combinations in cough-cold mixtures. The optimum composition of the mobile phase and the optimum flow rate were determined and are reported. The method was applied to the determination of active ingredients in seven commercially available cough-cold mixtures.

  5. Development of a pheromone elution rate physical model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A first principle modeling approach is applied to available data describing the elution of semiochemicals from pheromone dispensers. These data include field data for 27 products developed by several manufacturers, including homemade devices, as well as laboratory data collected on three semiochemi...

  6. Nanoporous Titanium Surfaces for Sustained Elution of Proteins and Antibiotics

    PubMed Central

    Cassani, Davide A. D.; Variola, Fabio

    2014-01-01

    Current medically relevant metals for prosthetic reconstructions enjoy a relatively good success rate, but their performance drops significantly in patients with compromised health status, and post-surgical infections still remain an important challenge. To address these problems, different nanotechnology-based strategies have been exploited to create implantable metals with an enhanced bioactivity and antibacterial capacities. Among these, oxidative nanopatterning has emerged as a very effective approach to engender nanoporous surfaces that stimulate and guide the activity of adhering cells. The resulting nanoporosity is also attractive because it offers nanoconfined volumes that can be exploited to load bioactive compounds and modulate their release over time. Such extended elution is needed since a single exposure to growth factors and/or antibiotics, for instance, may not be adequate to further sustain bone regeneration and/or to counteract bacterial colonization. In this article, we assessed the capacities of nanoporous titanium surfaces generated by oxidative nanopatterning to provide controlled and sustained elution of proteins and antibiotic molecules. To this end, we have selected bovine serum albumin (BSA) and vancomycin to reflect commonly used compounds, and investigated their adsorption and elution by Fourier-transform infrared (FT-IR) and ultraviolet–visible (UV-VIS) spectroscopy. Our results demonstrate that while the elution of albumin is not significantly affected by the nanoporosity, in the case of vancomycin, nanoporous surfaces provided an extended release. These findings were successively correlated to the establishment of interactions with the surface and physical-entrapment effects exerted by the nanopores, ultimately highlighting their synergistic contribution to the release profiles and thus their importance in the design of nanostructured eluting platforms for applications in medicine. PMID:24633020

  7. Ligand-assisted elution chromatography for separation of lanthanides.

    PubMed

    Ling, Lei; Wang, Nien-Hwa Linda

    2015-04-10

    Lanthanides (Ln's) are the major components of rare earth elements, which are critical components of many high-value products. The ions of adjacent Ln's have the same valence and very similar ionic radii. They cannot be separated using conventional adsorption or ion exchange processes. Current production of high-purity Ln's is based on multiple sequential and parallel solvent extraction processes, which require large amounts of toxic solvents and result in serious negative impact on the environment. In this study, a ligand-assisted elution chromatography process for the separation of Ln's was developed for the first time for titania, which is a robust and inexpensive inorganic sorbent. A selective ligand for Ln's, ethylenediaminetetraacetic acid (EDTA), was found to adsorb on the sorbent. The adsorbed EDTA became strong adsorption sites for the Ln's. Desorption of Ln's was driven by reversible reactions of Ln's with EDTA in the mobile phase. The overall sorbent selectivity for the reaction and adsorption process was approximately equal to the ratio of the sorbent selectivity to the ligand selectivity. The separation mechanisms were tested and verified using rate model simulations and experimental data for the separation of praseodymium (Pr), neodymium (Nd), and samarium (Sm). Simulations based on the model were used to design efficient linear gradient elution and stepwise elution processes. The purity and yield of all three Ln's were found to be above 95% in the designed processes. Stepwise elution can be implemented in a continuous process for increasing sorbent productivity and reducing costs for large-scale separation. Ligand assisted elution processes are much simpler and more environmentally friendly than the conventional solvent extraction processes. PMID:25746756

  8. Quantitative structure-retention relationships applied to liquid chromatography gradient elution method for the determination of carbonyl-2,4-dinitrophenylhydrazone compounds.

    PubMed

    Cirera-Domènech, Elisenda; Estrada-Tejedor, Roger; Broto-Puig, Francesc; Teixidó, Jordi; Gassiot-Matas, Miquel; Comellas, Lluís; Lliberia, Josep Lluís; Méndez, Alberto; Paz-Estivill, Susanna; Delgado-Ortiz, Maria Rosa

    2013-02-01

    A usual method for the determination of aldehydes and ketones in different matrices consists of a derivatization with 2,4-dinitrophenylhydrazine (DNPH) followed by HPLC-UV analysis. In the present work, a HPLC-UV gradient elution method has been applied to the analysis of 13 aldehydes and ketones-DNPH in automotive emission samples. In addition to these 13 compounds-DNPH, several carbonyl-DNPH compounds (linear, ramified and cyclic, saturated and unsaturated compounds) have been analyzed by HPLC-UV. Quantitative structure-retention relationships (QSRR) methods have been applied to predict the logarithm of capacity factor (logk') of carbonyl-DNPH compounds. According to its physicochemical meaning, combinations of 2 and 3 molecular descriptors have been proposed in order to achieve higher correlation with logk'. Using linear and non-linear QSRR methodologies, the resulting prediction models allowed the screening of the most probable carbonyl-DNPH derivative candidates that correspond to unknown compounds detected in automotive emission samples. This information has been useful for their identification by UPLC(®)-MS/MS. In addition, the chromatographic retention of different carbonyl-DNPH compound families was studied using two HPLC isocratic methods working with two orthogonal stationary phases (octadecylpolyethoxysilane and cyanopropyl). Differences between the retention indexes obtained for each column were used for classifying carbonyl-DNPH into compounds families. PMID:23298845

  9. Nanoparticles and drug eluting stents for disease detection and treatment

    NASA Astrophysics Data System (ADS)

    Meng, Juan

    This thesis presents the results of experimental and theoretical studies of nanoparticle entry/adhesion to breast cancer cells and adhesion in drug-eluting stents. Atomic Force Microscopy (AFM) techniques are used to quantify the adhesion. The thermodynamics and kinetics concepts are presented for the modeling of nanoparticle entry into breast cancer cells. In the case of the drug-eluting stents studies, a combination of adhesion theory and fracture mechanics concepts is used to estimate the adhesion energies. To investigate the specific accumulation of the functionalized super-paramagnetic iron oxide nanoparticles (SPIONs) in breast cancer cells, a combination of transmission electron microscopy (TEM) and spectrophotometric analysis was used. It is shown that SPIONs conjugated to luteinizing hormone releasing hormone (LHRH) (LHRH-SPIONs), can be used to specifically target breast cancer cells. They also act as contrast enhancement agents during the magnetic resonance imaging (MRI) of breast cancer xenografts. The adhesion between LHRH and breast cancer cells is an important factor for LHRH-SPIONs to target breast cancer cells. AFM techniques were used to quantify adhesion between LHRH peptides and their receptors on breast cancer cells. The adhesion force between LHRH-coated AFM tips and human breast cancer cells is shown to be about five times greater than that between LHRH-coated AFM tips and normal breast cells. This result also suggests that force microscopy can be used for the specific detection of breast cancer cells. Adhesion and fracture mechanics techniques were used to study the adhesion between the drug eluting layer and Parylene C layer coated onto a model drug-eluting stent. AFM force--displacement measurements were used to quantify the adhesion between the parylene C primer and the drug-eluting layer and the cohesion between the three constituents of the drug-eluting layer. Adhesion theories were then used to relate the measured forces to adhesion

  10. Elution of High Dose Amphotericin B Deoxycholate From Polymethylmethacrylate.

    PubMed

    Houdek, Matthew T; Greenwood-Quaintance, Kerryl E; Morrey, Mark E; Patel, Robin; Hanssen, Arlen D

    2015-12-01

    Fungal periprosthetic joint infections are rare, devastating complications of arthroplasty. There is conflicting evidence as to the efficacy of amphotericin B elution from cement spacers. The purpose of this study was to determine whether concentrations of amphotericin B released from bone cement over time would be efficacious in treating a periprosthetic infection. A continuous flow chamber was used to evaluate the in vitro release of amphotericin from cement beads containing 7.5% amphotericin. Following polymerization, 3.3% of the initially loaded amphotericin B was detected. The peak mean concentration eluted from the bone cement was 0.33 μg/mL at 8 hours. The AUC0-24 was 2.79 μg/mL/h; 0.20% of the amphotericin B was released. In conclusion, amphotericin B is released from bone cement at a clinically useful concentration.

  11. Late acute thrombosis after paclitaxel eluting stent implantation

    PubMed Central

    Liistro, F; Colombo, A

    2001-01-01

    Late (more than six months) total occlusion after coronary stenting is a progressive phenomenon occurring in approximately 4% of patients, leading to acute myocardial infarction in less than 0.5%. The process must be related to severe and progressive intimal hyperplasia. In patients receiving coronary stenting with simultaneous brachytherapy, late total occlusion has been reported at a higher rate and to be related to stent thrombosis rather than intimal hyperplasia. Late total occlusion presenting with an acute clinical event seven months after the implantation of a paclitaxel drug eluting stent is reported. The occlusion developed soon after the interruption of ticlopidine treatment, suggesting that the event had a thrombotic genesis and that the risk is not confined to the first six month period.


Keywords: paclitaxel eluting stent; late thrombosis PMID:11514475

  12. Suppression of scarring in peripheral nerve implants by drug elution

    NASA Astrophysics Data System (ADS)

    FitzGerald, James J.

    2016-04-01

    Objective. Medical implants made of non-biological materials provoke a chronic inflammatory response, resulting in the deposition of a collagenous scar tissue (ST) layer on their surface, that gradually thickens over time. This is a critical problem for neural interfaces. Scar build-up on electrodes results in a progressive decline in signal level because the scar tissue gradually separates axons away from the recording contacts. In regenerative sieves and microchannel electrodes, progressive scar deposition will constrict and may eventually choke off the sieve hole or channel lumen. Interface designs need to address this issue if they are to be fit for long term use. This study examines a novel method of inhibiting the formation and thickening of the fibrous scar. Approach. Research to date has mainly focused on methods of preventing stimulation of the foreign body response by implant surface modification. In this paper a pharmacological approach using drug elution to suppress chronic inflammation is introduced. Microchannel implants made of silicone doped with the steroid drug dexamethasone were implanted in the rat sciatic nerve for periods of up to a year. Tissue from within the microchannels was compared to that from control devices that did not release any drug. Main results. In the drug eluting implants the scar layer was significantly thinner at all timepoints, and unlike the controls it did not continue to thicken after 6 months. Control implants supported axon regeneration well initially, but axon counts fell rapidly at later timepoints as scar thickened. Axon counts in drug eluting devices were initially much lower, but increased rather than declined and by one year were significantly higher than in controls. Significance. Drug elution offers a potential long term solution to the problem of performance degradation due to scarring around neural implants.

  13. Optimization of Drug Delivery by Drug-Eluting Stents

    PubMed Central

    Bozsak, Franz; Gonzalez-Rodriguez, David; Sternberger, Zachary; Belitz, Paul; Bewley, Thomas; Chomaz, Jean-Marc; Barakat, Abdul I.

    2015-01-01

    Drug-eluting stents (DES), which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours) or very slowly (over periods of several months up to one year) at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices. PMID:26083626

  14. WE-G-BRE-08: Radiosensitization by Olaparib Eluting Nanospheres

    SciTech Connect

    Tangutoori, S; Kumar, R; Sridhar, S; Korideck, H; Makrigiorgos, G; Cormack, R

    2014-06-15

    Purpose: Permanent prostate brachytherapy often uses inert bio-absorbable spacers to achieve the desired geometric distribution of sources within the prostate. Transforming these spacers into implantable nanoplatforms for chemo-radiation therapy (INCeRT) provides a means of providing sustained in-situ release of radiosensitizers in the prostate to enhance the therapeutic ratio of the procedure. Olaparib, a PARP inhibitor, suppresses DNA repair processes present during low dose rate continuous irradiation. This work investigates the radiosensitizing/DNA damage repair inhibition by NanoOlaparib eluting nanospheres. Methods: Human cell line PC3 (from ATCC), was maintained in F12-k medium supplemented with fetal bovine serum. Clonogenic assay kit (from Fischer Scientific) was used to fix and stain the cells to determine the long term effects of irradiation. Nanoparticle size and zeta potential of nanospheres were determined using a Zeta particle size analyzer. The incorporation of Olaparib in nanospheres was evaluated by HPLC. Irradiation was performed in a small animal irradiator operating at 220 KeV.The long term effects of radio-sensitization with olaparib and nanoolaparib was determined using the clonogenic assay at 2 Gy and 4 Gy doses. The cells were allowed to grow for around 10 doubling cycles, The colonies were fixed and stained using clonogenic assay kit. The excess stain was washed off using DI water and the images were taken using a digital camera. Results: Radiosensitization studies were carried out in prostate cancer cell line, PC3 radiation at 0, 2 and 4Gy doses. Strongest dose response was observed with nanoolaparib treated cells compared to untreated cells. Conclusion: A two stage drug release of drug eluting nanospheres from a biodegradable spacer has been suggested for sustained in-situ release of Olaparib to suppress DNA repair processes during prostate brachytherapy. The Olaparib eluting nanospheres had the same in-vitro radiosensitizing effect as

  15. Drug-eluting balloons: future potential indications and applications.

    PubMed

    Choo, Gim-Hooi

    2011-05-01

    The drug-eluting balloon (DEB) is an exciting new technology that holds much promise. As an evolving technology undergoing intensive research, the device is being constantly refined and its numerous potential applications studied. Though initially created to fulfil specific needs in the coronary vasculature, there is great potential for its use in other vascular territories and structures including the management of valvular, congenital heart and neuro-interventional pathologies. In addition, the application of this device in conjunction with other existing technologies may enhance the clinical results. PMID:22027720

  16. Drug-eluting balloons: future potential indications and applications.

    PubMed

    Choo, Gim-Hooi

    2011-05-01

    The drug-eluting balloon (DEB) is an exciting new technology that holds much promise. As an evolving technology undergoing intensive research, the device is being constantly refined and its numerous potential applications studied. Though initially created to fulfil specific needs in the coronary vasculature, there is great potential for its use in other vascular territories and structures including the management of valvular, congenital heart and neuro-interventional pathologies. In addition, the application of this device in conjunction with other existing technologies may enhance the clinical results.

  17. Biodegradable-Polymer Biolimus-Eluting Stents versus Durable-Polymer Everolimus-Eluting Stents at One-Year Follow-Up: A Registry-Based Cohort Study.

    PubMed

    Parsa, Ehsan; Saroukhani, Sepideh; Majlessi, Fereshteh; Poorhosseini, Hamidreza; Lofti-Tokaldany, Masoumeh; Jalali, Arash; Salarifar, Mojtaba; Nematipour, Ebrahim; Alidoosti, Mohammad; Aghajani, Hassan; Amirzadegan, Alireza; Kassaian, Seyed Ebrahim

    2016-04-01

    We compared outcomes of percutaneous coronary intervention patients who received biodegradable-polymer biolimus-eluting stents with those who received durable-polymer everolimus-eluting stents. At Tehran Heart Center, we performed a retrospective analysis of the data from January 2007 through December 2011 on 3,270 consecutive patients with coronary artery disease who underwent percutaneous coronary intervention with the biodegradable-polymer biolimus-eluting stent or the durable-polymer everolimus-eluting stent. We excluded patients with histories of coronary artery bypass grafting or percutaneous coronary intervention, acute ST-segment-elevation myocardial infarction, or the implantation of 2 different stent types. Patients were monitored for 12 months. The primary endpoint was a major adverse cardiac event, defined as a composite of death, nonfatal myocardial infarction, and target-vessel and target-lesion revascularization. Durable-polymer everolimus-eluting stents were implanted in 2,648 (81%) and biodegradable-polymer biolimus-eluting stents in 622 (19%) of the study population. There was no significant difference between the 2 groups (2.7% vs 2.7%; P=0.984) in the incidence of major adverse cardiac events. The cumulative adjusted probability of major adverse cardiac events in the biodegradable-polymer biolimus-eluting stent group did not differ from that of such events in the durable-polymer everolimus-eluting stent group (hazard ratio=0.768; 95% confidence interval, 0.421-1.44; P=0.388). We conclude that in our patients the biodegradable-polymer biolimus-eluting stent was as effective and safe, during the 12-month follow-up period, as was the durable-polymer everolimus-eluting stent.

  18. Numerical modeling of elution peak profiles in supercritical fluid chromatography. Part I-Elution of an unretained tracer

    SciTech Connect

    Kaczmarski, Krzysztof; Guiochon, Georges A

    2010-01-01

    When chromatography is carried out with high-density carbon dioxide as the main component of the mobile phase (a method generally known as 'supercritical fluid chromatography' or SFC), the required pressure gradient along the column is moderate. However, this mobile phase is highly compressible and, under certain experimental conditions, its density may decrease significantly along the column. Such an expansion absorbs heat, cooling the column, which absorbs heat from the outside. The resulting heat transfer causes the formation of axial and radial gradients of temperature that may become large under certain conditions. Due to these gradients, the mobile phase velocity and most physico-chemical parameters of the system (viscosity, diffusion coefficients, etc.) are no longer constant throughout the column, resulting in a loss of column efficiency, even at low flow rates. At high flow rates and in serious cases, systematic variations of the retention factors and the separation factors with increasing flow rates and important deformations of the elution profiles of all sample components may occur. The model previously used to account satisfactorily for the effects of the viscous friction heating of the mobile phase in HPLC is adapted here to account for the expansion cooling of the mobile phase in SFC and is applied to the modeling of the elution peak profiles of an unretained compound in SFC. The numerical solution of the combined heat and mass balance equations provides temperature and pressure profiles inside the column, and values of the retention time and efficiency for elution of this unretained compound that are in excellent agreement with independent experimental data.

  19. Nano-scale adhesion in multilayered drug eluting stents.

    PubMed

    Youssefian, Sina; Rahbar, Nima

    2013-02-01

    Using stainless steel 316L for drug-eluting stents needs specific surface finishing due to corrosion phenomena that take place on the metal surface upon prolonged contact with human tissue. Poly (o-chloro-p-xylylene) (Parylene C) is one of the inert and biocompatible materials that are used for 316L coating with γ-methacryloxypropyltrimethoxysilane as an adhesion promoter. In this study, a combination of atomic force microscopy experiments and contact theories have been used to quantify the work of adhesion between parylene C/316L and silane added parylene C/316L. An atomistic simulation has been used, first, to investigate and compare the adhesion at the room temperature with the experiments and then, to investigate the effect of aqueous environment with higher temperature, inside the body, on the adhesion between layers in the structure of drug eluting stent. The simulation results of simplified model for 316L are in good agreement with the experimental results and suggest that the week affiliation between this polymer and 316L is mainly due to Van der Waals interactions. The effect of temperature on the adhesion is found to be regressive and as the water molecules permeate the polymer the adhesion decreases. They also imply that the effect of silane on the adhesion between parylene C and steel is modest.

  20. Drug-Eluting Fibers for HIV-1 Inhibition and Contraception

    PubMed Central

    Ball, Cameron; Krogstad, Emily; Chaowanachan, Thanyanan; Woodrow, Kim A.

    2012-01-01

    Multipurpose prevention technologies (MPTs) that simultaneously prevent sexually transmitted infections (STIs) and unintended pregnancy are a global health priority. Combining chemical and physical barriers offers the greatest potential to design effective MPTs, but integrating both functional modalities into a single device has been challenging. Here we show that drug-eluting fiber meshes designed for topical drug delivery can function as a combination chemical and physical barrier MPT. Using FDA-approved polymers, we fabricated nanofiber meshes with tunable fiber size and controlled degradation kinetics that facilitate simultaneous release of multiple agents against HIV-1, HSV-2, and sperm. We observed that drug-loaded meshes inhibited HIV-1 infection in vitro and physically obstructed sperm penetration. Furthermore, we report on a previously unknown activity of glycerol monolaurate (GML) to potently inhibit sperm motility and viability. The application of drug-eluting nanofibers for HIV-1 prevention and sperm inhibition may serve as an innovative platform technology for drug delivery to the lower female reproductive tract. PMID:23209601

  1. Drug-eluting stents to prevent stent thrombosis and restenosis.

    PubMed

    Im, Eui; Hong, Myeong-Ki

    2016-01-01

    Although first-generation drug-eluting stents (DES) have significantly reduced the risk of in-stent restenosis, they have also increased the long-term risk of stent thrombosis. This safety concern directly triggered the development of new generation DES, with innovations in stent platforms, polymers, and anti-proliferative drugs. Stent platform materials have evolved from stainless steel to cobalt or platinum-chromium alloys with an improved strut design. Drug-carrying polymers have become biocompatible or biodegradable and even polymer-free DES were introduced. New limus-family drugs (such as everolimus, zotarolimus or biolimus) were adopted to enhance stent performances. As a result, these new DES demonstrated superior vascular healing responses on intracoronary imaging studies and lower stent thrombotic events in actual patients. Recently, fully-bioresorbable stents (scaffolds) have been introduced, and expanding their applications. In this article, the important concepts and clinical results of new generation DES and bioresorbable scaffolds are described. PMID:26567863

  2. Neoatherosclerosis after Drug-Eluting Stent Implantation: Roles and Mechanisms

    PubMed Central

    Cui, Yuanyuan; Shi, Dazhuo; Chen, Keji

    2016-01-01

    In-stent neoatherosclerosis (NA), characterized by a relatively thin fibrous cap and large volume of yellow-lipid accumulation after drug-eluting stents (DES) implantation, has attracted much attention owing to its close relationship with late complications, such as revascularization and late stent thrombosis (ST). Accumulating evidence has demonstrated that more than one-third of patients with first-generation DES present with NA. Even in the advent of second-generation DES, NA still occurs. It is indicated that endothelial dysfunction induced by DES plays a critical role in neoatherosclerotic development. Upregulation of reactive oxygen species (ROS) induced by DES implantation significantly affects endothelial cells healing and functioning, therefore rendering NA formation. In light of the role of ROS in suppression of endothelial healing, combining antioxidant therapies with stenting technology may facilitate reestablishing a functioning endothelium to improve clinical outcome for patients with stenting. PMID:27446509

  3. Drug-eluting stents to prevent stent thrombosis and restenosis.

    PubMed

    Im, Eui; Hong, Myeong-Ki

    2016-01-01

    Although first-generation drug-eluting stents (DES) have significantly reduced the risk of in-stent restenosis, they have also increased the long-term risk of stent thrombosis. This safety concern directly triggered the development of new generation DES, with innovations in stent platforms, polymers, and anti-proliferative drugs. Stent platform materials have evolved from stainless steel to cobalt or platinum-chromium alloys with an improved strut design. Drug-carrying polymers have become biocompatible or biodegradable and even polymer-free DES were introduced. New limus-family drugs (such as everolimus, zotarolimus or biolimus) were adopted to enhance stent performances. As a result, these new DES demonstrated superior vascular healing responses on intracoronary imaging studies and lower stent thrombotic events in actual patients. Recently, fully-bioresorbable stents (scaffolds) have been introduced, and expanding their applications. In this article, the important concepts and clinical results of new generation DES and bioresorbable scaffolds are described.

  4. Neoatherosclerosis after Drug-Eluting Stent Implantation: Roles and Mechanisms

    PubMed Central

    Cui, Yuanyuan; Shi, Dazhuo; Chen, Keji

    2016-01-01

    In-stent neoatherosclerosis (NA), characterized by a relatively thin fibrous cap and large volume of yellow-lipid accumulation after drug-eluting stents (DES) implantation, has attracted much attention owing to its close relationship with late complications, such as revascularization and late stent thrombosis (ST). Accumulating evidence has demonstrated that more than one-third of patients with first-generation DES present with NA. Even in the advent of second-generation DES, NA still occurs. It is indicated that endothelial dysfunction induced by DES plays a critical role in neoatherosclerotic development. Upregulation of reactive oxygen species (ROS) induced by DES implantation significantly affects endothelial cells healing and functioning, therefore rendering NA formation. In light of the role of ROS in suppression of endothelial healing, combining antioxidant therapies with stenting technology may facilitate reestablishing a functioning endothelium to improve clinical outcome for patients with stenting.

  5. In vivo Evaluation of Cenderitide-Eluting Stent (CES) II.

    PubMed

    Huang, Yingying; Ng, Xu Wen; Lim, Soon Ghim; Chen, Horng Haur; Burnett, John C; Boey, Yin Chiang Freddy; Venkatraman, Subbu S

    2016-02-01

    The use of drug-eluting coronary stents has led to significant reduction in in-stent restenosis (ISR), but led to delayed endothelialization, necessitating the prolonged use of expensive anti-thrombotic drugs with their side-effects. Cenderitide (CD-NP) is a novel anti-proliferative chimeric peptide of semi-endothelial origin. Our previous work in vitro has demonstrated; that the smooth muscle cells were inhibited significantly more than endothelial cells which is the desirable feature of an anti-restenosis drug. This work reports the effects of implantation of a centeritide-eluting stent (CES) on ISR and endothelialization in an in vivo model. CESs were produced by coating bare metallic stents with CD-NP entrapped in biodegradable poly(ε-caprolactone) using an ultrasonic spray coater. A total of 32 stents were successfully implanted into 16 pigs, and all animal survived for 28 days. The plasma levels of CD-NP were significantly higher in the CES group than in the control group (bare metal stents and polymer-coated stent) at post-stenting, indicating the successful release of CD-NP from the stent in vivo. Furthermore, SEM analysis results showed the greater endothelial coverage of the stent struts, as well as between the struts in CES group. Moreover, histological results showed mild inflammation, and low fibrin score at 28 days. However, plasma cGMP (second messenger, cyclic 3',5' guanosine monophosphate) does not show a significant difference, and the CES is also unable to show significant difference in terms on neointimal area and stenosis, in comparison to BMS at 28 days.

  6. Determinants of protein elution rates from preparative ion-exchange adsorbents.

    PubMed

    Angelo, James M; Lenhoff, Abraham M

    2016-04-01

    The rate processes involved in elution in preparative chromatography can affect both peak resolution and hence selectivity as well as practical factors such as facility fit. These processes depend on the physical structure of the adsorbent particles, the amount of bound solute, the solution conditions for operation or some combination of these factors. Ion-exchange adsorbents modified with covalently attached or grafted polymer layers have become widely used in preparative chromatography. Their often easily accessible microstructures offer substantial binding capacities for biomolecules, but elution has sometimes been observed to be undesirably slow. In order to determine which physicochemical phenomena control elution behavior, commercially available cellulosic, dextran-grafted and unmodified agarose materials were characterized here by their elution profiles at various conditions, including different degrees of loading. Elution data were analyzed under the assumption of purely diffusion-limited control, including the role of pore structure properties such as porosity and tortuosity. In general, effective elution rates decreased with the reduction of accessible pore volume, but differences among different proteins indicated the roles of additional factors. Additional measurements and analysis, including the use of confocal laser scanning microscopy to observe elution within single chromatographic particles, indicated the importance of protein association within the particle during elution. The use of protein stabilizing agents was explored in systems presenting atypical elution behavior, and l-arginine and disaccharide excipients were shown to alleviate the effects for one protein, lysozyme, in the presence of sodium chloride. Incorporation of these excipients into eluent buffer gave rise to faster elution and significantly lower pool volumes in elution from polymer-modified adsorbents.

  7. Ion exchange chromatography of proteins-predictions of elution curves and operating conditions. II. Experimental verification.

    PubMed

    Yamamoto, S; Nakanishi, K; Matsuno, R; Kamijubo, T

    1983-05-01

    The applicability and validity of the model developed in Part I were confirmed experimentally. In this article, various proteins were eluted both by stepwise and linear gradient elution on DEAE ion exchangers under a variety of experimental conditions. Adsorption isotherms were measured as a function of ionic strength in batch experiments. The moment method was employed for the determination of various parameters such as the gel-phase diffusion coefficient and the longitudinal dispersion coefficient. By use of these parameters and the experimentally measured ionic strength of the peak position, the number of plates was determined according to the method described in Part I. Theoretical elution curves were calculated with the experimentally measured adsorption equilibria and the number of plates. Good agreement was observed between theory an experiments. Various factors affecting the separation were investigated. It was found that the effect of the number of plates for salts, N'(p), was negligible except the case of stepwise elution of high ionic strength buffer. When elution curves were symmetrical, the widths of the elution curves were inversely proportional to the square root of the number of plates of proteins, N(p), as in other chromatographic techniques. A simple graphical method for prediction of the peak position in linear gradient elution described in Part I was found applicable when the elution curves were symmetrical. A useful correlation of prediction of the peak width in a linear gradient elution was proposed on the basis of the approximate solution derived in Part I of this study. This graphical method and correlation permit easy prediction of the peak position and peak width in linear gradient elution in the case of symmetrical elution curves.

  8. Randomized clinical trial comparing abluminal biodegradable polymer sirolimus-eluting stents with durable polymer sirolimus-eluting stents

    PubMed Central

    Zhang, Haijun; Wang, Xiangfei; Deng, Wei; Wang, Shenguo; Ge, Junbo; Toft, Egon

    2016-01-01

    Abstract Background: The biodegradable polymer drug-eluting stents (DES) were developed to improve vascular healing. However, further data and longer-term follow-up are needed to confirm safety and efficacy of these stents. This randomized clinical trial aimed to compare safety and efficacy of 2 sirolimus-eluting stents (SES): Cordimax—a novel abluminal biodegradable polymer SES and Cypher Select—a durable polymer SES, at 9 months angiographic and 5-year clinical follow-up. Methods: We randomized 402 patients with coronary artery disease to percutaneous coronary intervention with Cordimax (n = 202) or Cypher select (n = 200). Angiographic follow-up was performed at 9 months after the index procedure and clinical follow-up annually up to 5 years. The primary endpoint was angiographic in-stent late luminal loss (LLL). Secondary endpoints included angiographic restenosis rate, target vessel revascularization (TVR), and major adverse cardiac events (MACEs; defined as cardiac death, myocardial infarction, or TVR) at 5-year follow-up. Results: Cordimax was noninferior to Cypher select for in-stent LLL (0.25 ± 0.47 vs 0.18 ± 0.49 mm; P = 0.587) and in-stent mean diameter stenosis (22.19 ± 12.21% vs 19.89 ± 10.79%; P = 0.064) at 9 months angiographic follow-up. The MACE rates were not different at 1 year (5.9% vs 4.0%, P = 0.376); however, MACE rates from 2 to 5 years were lower in the Cordimax group (6.8% vs 13.1%; P = 0.039). Conclusion: Abluminal biodegradable polymer SES is noninferior to durable polymer SES at 9-month angiographic and 1-year clinical follow-up. However, MACE rates from 2 to 5 years were less in the abluminal biodegradable polymer group. PMID:27661023

  9. Zotarolimus-eluting stent fracture at initial implantation diagnosed with StentBoost

    PubMed Central

    Arat Ozkan, Alev; Sinan, Umit Yasar; Gurmen, Aziz T

    2016-01-01

    Stent fracture is a rare complication of drug-eluting stent implantation with a reported rate of 0.84%–3.2% in various clinical studies with first-generation drug-eluting stents and 29% in autopsy studies. Sirolimus-eluting stents with their closed cell design were reported to be more prone to fracture compared to paclitaxel-eluting stents. Other risk factors for stent fracture are multiple stenting, longer stent length, chronic renal failure, right coronary artery intervention, and a higher maximal inflation pressure. The role of angiography in diagnosing stent fracture is limited, a fact also questioning the reliability of angiographic data. Image enhancement techniques like StentBoost are widely available in new-generation angiography systems and are used to assess stent expansion, overlap size, or to localize the postdilation balloon. Here, we report a case of zotarolimus-eluting stent fracture at initial implantation diagnosed with StentBoost. PMID:27489714

  10. Zotarolimus-eluting stent fracture at initial implantation diagnosed with StentBoost.

    PubMed

    Arat Ozkan, Alev; Sinan, Umit Yasar; Gurmen, Aziz T

    2016-01-01

    Stent fracture is a rare complication of drug-eluting stent implantation with a reported rate of 0.84%-3.2% in various clinical studies with first-generation drug-eluting stents and 29% in autopsy studies. Sirolimus-eluting stents with their closed cell design were reported to be more prone to fracture compared to paclitaxel-eluting stents. Other risk factors for stent fracture are multiple stenting, longer stent length, chronic renal failure, right coronary artery intervention, and a higher maximal inflation pressure. The role of angiography in diagnosing stent fracture is limited, a fact also questioning the reliability of angiographic data. Image enhancement techniques like StentBoost are widely available in new-generation angiography systems and are used to assess stent expansion, overlap size, or to localize the postdilation balloon. Here, we report a case of zotarolimus-eluting stent fracture at initial implantation diagnosed with StentBoost. PMID:27489714

  11. Prognostic Significance of Polymer Coatings in Zotarolimus-Eluting Stents.

    PubMed

    Iqbal, M Bilal; Nadra, Imad J; Din, Jehangir N; Hendry, Cara; Ding, Lillian; Fung, Anthony; Aymong, Eve; Chan, Albert W; Hodge, Steven; Robinson, Simon D; Della Siega, Anthony

    2016-03-01

    Polymer coatings on drug-eluting stents (DES) serve as a vehicle for delivery of antirestenotic drugs. Whether they influence outcomes for contemporary DES is unknown. The evolution of polymer coatings for zotarolimus-eluting stents (ZES) provides a natural experiment that facilitates such analysis. The Resolute ZES (R-ZES) uses the same antirestenotic drug as the Endeavor ZES (E-ZES) but has a more biocompatible polymer with enhanced drug release kinetics. However, there are limited data on the real-world comparative efficacy of R-ZES and the preceding E-ZES. Thus, we analyzed 17,643 patients who received either E-ZES or R-ZES from 2008 to 2014 from the British Columbia Cardiac Registry. A total of 9,869 patients (56%) received E-ZES and 7,774 patients (44%) received R-ZES. Compared with E-ZES, R-ZES was associated with lower 2-year mortality (4.1% vs 6.4%, p <0.001) and 2-year target vessel revascularization (TVR; 6.8% vs 10.7%, p <0.001). R-ZES use was an independent predictor of lower mortality rate and TVR. This was confirmed in propensity-matched analyses for 2-year mortality (hazard ratio [HR] 0.59, 95% CI 0.49 to 0.71, p <0.001) and 2-year TVR (HR 0.86, 95% CI 0.75 to 0.98, p = 0.032). Instrumental variable analyses demonstrated R-ZES to be associated with lower 2-year mortality (Δ = -2.2%, 95% CI -4.3% to -0.2%, p = 0.032) and 2-year TVR (Δ = -3.3% to 95% CI -6.1% to -0.7%, p = 0.015). Acknowledging the limitations of observational analyses, this study has shown that R-ZES was associated with lower long-term TVR and mortality. These data are reassuring for the newer R-ZES and demonstrate how polymer coatings may influence the clinical performance of DES with wider implications for future DES development and design. PMID:26796194

  12. Sequential Elution Interactome Analysis of the Mind Bomb 1 Ubiquitin Ligase Reveals a Novel Role in Dendritic Spine Outgrowth*

    PubMed Central

    Mertz, Joseph; Tan, Haiyan; Pagala, Vishwajeeth; Bai, Bing; Chen, Ping-Chung; Li, Yuxin; Cho, Ji-Hoon; Shaw, Timothy; Wang, Xusheng; Peng, Junmin

    2015-01-01

    The mind bomb 1 (Mib1) ubiquitin ligase is essential for controlling metazoan development by Notch signaling and possibly the Wnt pathway. It is also expressed in postmitotic neurons and regulates neuronal morphogenesis and synaptic activity by mechanisms that are largely unknown. We sought to comprehensively characterize the Mib1 interactome and study its potential function in neuron development utilizing a novel sequential elution strategy for affinity purification, in which Mib1 binding proteins were eluted under different stringency and then quantified by the isobaric labeling method. The strategy identified the Mib1 interactome with both deep coverage and the ability to distinguish high-affinity partners from low-affinity partners. A total of 817 proteins were identified during the Mib1 affinity purification, including 56 high-affinity partners and 335 low-affinity partners, whereas the remaining 426 proteins are likely copurified contaminants or extremely weak binding proteins. The analysis detected all previously known Mib1-interacting proteins and revealed a large number of novel components involved in Notch and Wnt pathways, endocytosis and vesicle transport, the ubiquitin-proteasome system, cellular morphogenesis, and synaptic activities. Immunofluorescence studies further showed colocalization of Mib1 with five selected proteins: the Usp9x (FAM) deubiquitinating enzyme, alpha-, beta-, and delta-catenins, and CDKL5. Mutations of CDKL5 are associated with early infantile epileptic encephalopathy-2 (EIEE2), a severe form of mental retardation. We found that the expression of Mib1 down-regulated the protein level of CDKL5 by ubiquitination, and antagonized CDKL5 function during the formation of dendritic spines. Thus, the sequential elution strategy enables biochemical characterization of protein interactomes; and Mib1 analysis provides a comprehensive interactome for investigating its role in signaling networks and neuronal development. PMID:25931508

  13. The diabetic dilemma: which drug-eluting stent works best?

    PubMed

    Ielasi, A; Latib, A; Colombo, A

    2014-02-01

    The relationship between diabetes mellitus and coronary artery disease is well established. The percentage of patients participating in clinical trials of percutaneous coronary intervention (PCI) who have diabetes is quickly rising. Diabetic patients have a worse prognosis than non-diabetics, with generally greater rates of death, myocardial infarction and need for target lesion and vessel revascularization. Stenting has improved the outcome of diabetic patients receiving PCI. Compared with bare-metal stents, the use of drug-eluting stents has resulted in a significant reduction in late lumen loss, binary restenosis, and clinically driven target vessel revascularization even in diabetic patients. Although surgical revascularization remains the recommended revascularization strategy for diabetics, particularly in case of multivessel coronary artery disease, recent progress in interventional devices and techniques have resulted in a changing paradigm for coronary artery revascularization. New stent designs, polymers and drugs are resulting in better outcomes overall, but more research is required to define their relative efficacy relative to other treatment options in this complex subgroup of patients. PMID:24500216

  14. Pacing impedance variability in tined steroid eluting leads.

    PubMed

    Danilovic, D; Ohm, O J

    1998-07-01

    The aim of the study was to investigate pacing impedance (PI) behavior in ambulatory patients. Eighteen atrial and 18 ventricular tined steroid eluting leads with 1.2-mm2 and 5.6-mm2 electrodes were implanted in 20 patients. At 9-27 months after implantation PI was measured automatically by means of additional algorithms downloaded via telemetry links into implanted Thera pulse generators. PI was determined based on the voltage drop on the output capacitor during the 5 V-1 ms pacing impulse, at the programmable sampling rates from 1 second to 30 minutes. The study examined in particular: (1) PI trends and variations associated with different breathing patterns, body postures, provocative maneuvers, bike exercise, and during 24 hours; (2) impact of pacing rate and AV-delay on PI; (3) correlation between PI variability and pacing threshold, lead configuration, absolute PI value, age, gender, disease, and cardiac chamber. The most important findings were: (1) large PI variations of up to 450 omega were observed in properly functioning leads, (2) PI variability exhibited a weak negative correlation with pacing thresholds as if electrode positional stability was not a major factor underlying PI variations, (3) unipolar and bipolar PI variations were equivalent to each other (correlation factor = 0.93) implying that PI was mostly dependent on the circumstances around the lead tip.

  15. The ultimate band compression factor in gradient elution chromatography

    SciTech Connect

    Gritti, Fabrice; Guiochon, Georges A

    2008-01-01

    The equations predicting the ultimate time band compression factor, G = (t{sub R}-t{sub F})/t{sub p} in linear gradient elution chromatography, for an infinitely narrow injection (injection time t{sub p} {yields} 0) were derived for an ideal-model column (dispersionless chromatography, H = 0) assuming the Linear Solvent Strength Model for the retention behavior of the analyte. Numerical solutions can readily be obtained when the LSSM model does not apply. The results can be generalized to any retained organic modifier (k'{sub A}) in the mobile phase. The stronger the retention of the organic modifier, the more effective the band compression. Dispersion in real chromatographic column (H {ne} 0) affects the limits that can be reached in linear gradients but poorly in step gradients. Examples based on a conventional HETP of about 12 {micro}m using a 5 {micro}m particle packed column reveal that the best time compression factor that could be expected is twice the one predicted with an ideal column.

  16. Bioresorbable polymer coated drug eluting stent: a model study.

    PubMed

    Rossi, Filippo; Casalini, Tommaso; Raffa, Edoardo; Masi, Maurizio; Perale, Giuseppe

    2012-07-01

    In drug eluting stent technologies, an increased demand for better control, higher reliability, and enhanced performances of drug delivery systems emerged in the last years and thus offered the opportunity to introduce model-based approaches aimed to overcome the remarkable limits of trial-and-error methods. In this context a mathematical model was studied, based on detailed conservation equations and taking into account the main physical-chemical mechanisms involved in polymeric coating degradation, drug release, and restenosis inhibition. It allowed highlighting the interdependence between factors affecting each of these phenomena and, in particular, the influence of stent design parameters on drug antirestenotic efficacy. Therefore, the here-proposed model is aimed to simulate the diffusional release, for both in vitro and the in vivo conditions: results were verified against various literature data, confirming the reliability of the parameter estimation procedure. The hierarchical structure of this model also allows easily modifying the set of equations describing restenosis evolution to enhance model reliability and taking advantage of the deep understanding of physiological mechanisms governing the different stages of smooth muscle cell growth and proliferation. In addition, thanks to its simplicity and to the very low system requirements and central processing unit (CPU) time, our model allows obtaining immediate views of system behavior.

  17. Webbing and Delamination of Drug Eluting Stent Coatings.

    PubMed

    Hopkins, C; Sweeney, C A; O'Connor, C; McHugh, P E; McGarry, J P

    2016-02-01

    The advancement of the drug-eluting stent technology raises the significant challenge of safe mechanical design of polymer coated stent systems. Experimental images of stent coatings undergoing significant damage during deployment have been reported; such coating damage and delamination can lead to complications such as restenosis and increased thrombogenicity. In the current study a cohesive zone modeling framework is developed to predict coating delamination and buckling due to hinge deformation during stent deployment. Models are then extended to analyze, for the first time, stent-coating damage due to webbing defects. Webbing defects occur when a bond forms between coating layers on adjacent struts, resulting in extensive delamination of the coating from the strut surfaces. The analyzes presented in this paper uncover the mechanical factors that govern webbing induced coating damage. Finally, an experimental fracture test of a commercially available stent coating material is performed and results demonstrate that the high cohesive strength of the coating material will prevent web fracture, resulting in significant coating delamination during stent deployment.

  18. Silver ions eluted from partially protected silver nanoparticles.

    PubMed

    Heidari Zare, Hamideh; Düttmann, Oliver; Vass, Attila; Franz, Gerhard; Jocham, Dieter

    2016-01-01

    The most prominent character of a new type of antibacterial urological catheters is the zebra-stripe pattern of a silver film, which is plated electroless on their interior wall and capped by a very thin semipermeable layer of parylene. This design effectively controls the release rate of Ag(+) ions in artificial urine, which has been measured as function of time with optical emission spectroscopy. By evaluating the minimum inhibitory concentration against certain strains of bacteria with solutions of AgNO3 of known concentration with the method of optical density and applying this analysis to the silver-eluting catheters, it was shown that this moderation prolongs the period of their application significantly. But to act as antibacterial agent in chlorine-containing solutions, as in urine, the presence of urea is required to avoid precipitation of AgCl and to meet or even exceed the minimum inhibitory concentration of Ag(+). The quality of the silver depot layer was further determined by the deposition rate and its morphology, which revealed that the film consisted of grains with a mean size of 150 nm. PMID:27400747

  19. Pacing impedance variability in tined steroid eluting leads.

    PubMed

    Danilovic, D; Ohm, O J

    1998-07-01

    The aim of the study was to investigate pacing impedance (PI) behavior in ambulatory patients. Eighteen atrial and 18 ventricular tined steroid eluting leads with 1.2-mm2 and 5.6-mm2 electrodes were implanted in 20 patients. At 9-27 months after implantation PI was measured automatically by means of additional algorithms downloaded via telemetry links into implanted Thera pulse generators. PI was determined based on the voltage drop on the output capacitor during the 5 V-1 ms pacing impulse, at the programmable sampling rates from 1 second to 30 minutes. The study examined in particular: (1) PI trends and variations associated with different breathing patterns, body postures, provocative maneuvers, bike exercise, and during 24 hours; (2) impact of pacing rate and AV-delay on PI; (3) correlation between PI variability and pacing threshold, lead configuration, absolute PI value, age, gender, disease, and cardiac chamber. The most important findings were: (1) large PI variations of up to 450 omega were observed in properly functioning leads, (2) PI variability exhibited a weak negative correlation with pacing thresholds as if electrode positional stability was not a major factor underlying PI variations, (3) unipolar and bipolar PI variations were equivalent to each other (correlation factor = 0.93) implying that PI was mostly dependent on the circumstances around the lead tip. PMID:9670178

  20. EVALUATION OF POTENTIAL ELUANTS FOR NON-ACID ELUTION OF CESIUM FROM SPHERICAL RESORCINOL-FORMALDEHYDE RESIN

    SciTech Connect

    Adu-Wusu, K.; Nash, C.; Pennebaker, F.

    2011-10-23

    Ion Exchange column loading and elution of cesium from spherical resorcinol-formaldehyde resin have been conducted for two potential non-acid eluants -(NH{sub 4}){sub 2}CO{sub 3} and CH{sub 3}COONH{sub 4}. The results revealed encouraging cesium elution performance. 100% elution was achieved in at most 22 hours ({approx}28 bed volumes) of elution. Elution performance was fairly high at 6 hours ({approx}8 bed volumes) of elution for some of the eluants and also practically comparable to the benchmark acid eluant (HNO{sub 3}). Hence, it is quite possible 100% percent elution will be closer to the 6th hour than the 22nd hour. Elution is generally enhanced by increasing the concentration and pH of the eluants, and combining the eluants.

  1. Exploring doxorubicin localization in eluting TiO2 nanotube arrays through fluorescence correlation spectroscopy analysis.

    PubMed

    De Santo, Ilaria; Sanguigno, Luigi; Causa, Filippo; Monetta, Tullio; Netti, Paolo A

    2012-11-01

    Drug elution properties of TiO(2) nanotube arrays have been largely investigated by means of solely macroscopic observations. Controversial elution performances have been reported so far and a clear comprehension of these phenomena is still missing as a consequence of a lack of molecular investigation methods. Here we propose a way to discern drug elution properties of nanotubes through the evaluation of drug localization by Fluorescence Correlation Spectroscopy (FCS) analysis. We verified this method upon doxorubicin elution from differently loaded TiO(2) nanotubes. Diverse elution profiles were obtained from nanotubes filled by soaking and wet vacuum impregnation methods. Impregnated nanotubes controlled drug diffusion up to thirty days, while soaked samples completed elution in seven days. FCS analysis of doxorubicin motion in loaded nanotubes clarified that more than 90% of drugs dwell preferentially in inter-nanotube spaces in soaked samples due to decorrelation in a 2D fashion, while a 97% fraction of molecules showed 1D mobility ascribable to displacements along the nanotube vertical axis of wet vacuum impregnated nanotubes. The diverse drug localizations inferred from FCS measurements, together with distinct drug-surface interaction strengths resulting from diverse drug filling techniques, could explain the variability in elution kinetics.

  2. Elution of benzo(a)pyrene from carbon blacks into biomembranes in vitro

    SciTech Connect

    Bevan, D.R.; Worrell, W.J.

    1985-01-01

    Elution of benzo(a)pyrene (BaP) from carbon blacks into phospholipid vesicles composed of dimyristoyl phosphatidylcholine (DMPC) or dipalmitoyl phosphatidylcholine (DPPC) was investigated. Samples of rubber-grade carbon blacks designated N-234, N-339, N-351, and N-375 containing exogenously adsorbed BaP were prepared by solvent extracting endogenous compounds from the carbon blacks and then readsorbing BaP at the desired concentrations. Concentrations of exogenous BaP on the carbon blacks were approximately 100-fold higher than normally occur on commercial carbon blacks, but the higher levels were used to improve the ability to detect elution of BaP into membranes. Elution of BaP from carbon blacks was studied using a fluorescence spectroscopic technique. Elution from N-234 was below detection limits of the system. Elution of BaP from N-339, N-351, and N-375 into DMPC and DPPC vesicles occurred in a biphasic manner. Elution occurred within 60 min of mixing carbon blacks with vesicles, although not all BaP was eluted from the particles. When the concentration of BaP adsorbed to N-375 was reduced, the rate and extent of elution were lowered. Extent of elution of BaP in these experiments may be greater than that of endogenous BaP on commercial carbon blacks because of the considerably higher quantities of exogenous BaP present. Furthermore, solvent extraction of endogenous materials prior to readsorption of BaP may alter the adsorption characteristics.

  3. Drug eluting biliary stents to decrease stent failure rates: A review of the literature

    PubMed Central

    Shatzel, Joseph; Kim, Jisoo; Sampath, Kartik; Syed, Sharjeel; Saad, Jennifer; Hussain, Zilla H; Mody, Kabir; Pipas, J Marc; Gordon, Stuart; Gardner, Timothy; Rothstein, Richard I

    2016-01-01

    Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy. PMID:26839648

  4. Inflammation and impaired wound healing after zotarolimus-eluting stent implantation.

    PubMed

    Yoneda, Shuichi; Abe, Shichiro; Taguchi, Isao; Masawa, Nobuhide; Inoue, Katsumi; Inoue, Teruo

    2012-01-01

    An 86-year-old man died suddenly 5 months after implantation of a zotarolimus-eluting stent. Two zotarolimus-eluting stents were placed to treat a highly calcified diffuse lesion in the proximal-to-mid right coronary artery. The lesion was fully covered by the two stents, and intravascular ultrasound showed complete stent apposition. However, an X-ray at autopsy showed that the proximal stent was fractured. Although we thought that thrombotic occlusion at the fracture site might have caused his sudden death, no thrombus was present. In addition, in the other sites where the stents were optimally dilated, there was stent malapposition and peri-strut inflammation including macrophage infiltration, giant cells, polymer phagocytosis, and neovascularization in the neointima. Even with a second-generation drug-eluting stent, such as the zotarolimus-eluting stent, wound healing may be impaired at the stent-injured vessel site.

  5. Clinicians' perspectives on the use of drug-eluting contact lenses for the treatment of glaucoma.

    PubMed

    Taniguchi, Elise V; Kalout, Patricia; Pasquale, Louis R; Kohane, Daniel S; Ciolino, Joseph B

    2014-10-01

    Glaucoma is the leading cause of irreversible blindness worldwide. The perspective of clinicians who treat the disease is important and may ultimately dictate the adoption of new treatment modalities, such as drug-eluting contact lenses. Recent advances have enabled contact lenses to serve as a sustained-release drug-delivery platform capable of treating glaucoma. This review covers the medical treatment of glaucoma, suboptimal adherence rates to treatment, and factors that may influence the clinical applicability of drug-eluting contact lenses. Ophthalmologists who treat glaucoma were surveyed to determine their perspective on treatment adherence, bandage contact lens use and the use of a drug-eluting contact lens to treat glaucoma. Given the challenge of treating glaucoma and the clinical need for improved drug delivery, drug-eluting contact lenses appear to be a promising treatment option.

  6. Purification of proteins specifically binding human endogenous retrovirus K long terminal repeat by affinity elution chromatography.

    PubMed

    Trubetskoy, D O; Zavalova, L L; Akopov, S B; Nikolaev, L G

    2002-11-01

    A novel affinity elution procedure for purification of DNA-binding proteins was developed and employed to purify to near homogeneity the proteins recognizing a 21 base pair sequence within the long terminal repeat of human endogenous retroviruses K. The approach involves loading the initial protein mixture on a heparin-agarose column and elution of protein(s) of interest with a solution of double-stranded oligonucleotide containing binding sites of the protein(s). The affinity elution has several advantages over conventional DNA-affinity chromatography: (i) it is easier and faster, permitting to isolate proteins in a 1 day-one stage procedure; (ii) yield of a target protein is severalfold higher than that in DNA-affinity chromatography; (iii) it is not necessary to prepare a special affinity support for each factor to be isolated. Theaffinity elution could be a useful alternative to conventional DNA-affinity chromatography.

  7. EVALUATION OF POTENTIAL ELUANTS FOR NON-ACID ELUTION OF CESIUM FROM RESORCINOL-FORMALDEHYDE RESIN

    SciTech Connect

    Adu-Wusu, K.; Pennebaker, F.

    2010-12-22

    Small-column ion exchange (SCIX) units installed in high-level waste tanks to remove Cs-137 from highly alkaline salt solutions are among the waste treatment plans in the DOE-complex. Spherical Resorcinol-Formaldehyde (sRF) is the ion exchange resin selected for use in the Hanford Waste Treatment and Immobilization Plant (WTP). It is also the primary ion exchange material under consideration for SCIX at the Hanford site. The elution step of the multi-step ion exchange process is typically done with 0.5 M nitric acid. An acid eluant is a potential hazard in the event of a spill, leak, etc. because the high-level waste tanks are made of carbon steel. Corrosion and associated structural damage may ensue. A study has been conducted to explore non-acid elution as an alternative. Batch contact sorption equilibrium screening tests have been conducted with 36 potential non-acid eluants. The sorption tests involve equilibrating each cesium-containing eluant solution with the sRF resin for 48 hours at 25 C in a shaker oven. In the sorption tests, an eluant is deemed to have a high cesium elution potential if it minimizes cesium sorption onto the sRF resin. The top candidates (based on lowest cesium sorption distribution coefficients) include ammonium carbonate, ammonium carbonate/ammonium hydroxide, ammonium bicarbonate, rubidium carbonate, ammonium acetate, ammonium acetate/ammonium hydroxide, ammonium bicarbonate/ammonium hydroxide, calcium chloride, and magnesium chloride. A select few of the top candidate eluants from the screening tests were subjected to actual sorption (loading) and elution tests to confirm their elution ability. The actual sorption (loading) and elution tests mimicked the typical sRF-cesium ion exchange process (i.e., sorption or loading, caustic wash, water rinse, and elution) via batch contact sorption and quasi column caustic wash/water rinse/elution. The eluants tested included ammonium carbonate, ammonium acetate, calcium acetate, magnesium

  8. Oral Factors Affecting Titanium Elution and Corrosion: An In Vitro Study Using Simulated Body Fluid

    PubMed Central

    Suito, Hideki; Iwawaki, Yuki; Goto, Takaharu; Tomotake, Yoritoki; Ichikawa, Tetsuo

    2013-01-01

    Objectives Ti, which is biocompatible and resistant to corrosion, is widely used for dental implants, particularly in patients allergic to other materials. However, numerous studies have reported on Ti allergy and the in vitro corrosion of Ti. This study investigated the conditions that promote the elution of Ti ions from Ti implants. Methods Specimens of commercially pure Ti, pure nickel, a magnetic alloy, and a gold alloy were tested. Each specimen was immersed in a simulated body fluid (SBF) whose pH value was controlled (2.0, 3.0, 5.0, 7.4, and 9.0) using either hydrochloric or lactic acid. The parameters investigated were the following: duration of immersion, pH of the SBF, contact with a dissimilar metal, and mechanical stimulus. The amounts of Ti ions eluted were measured using a polarized Zeeman atomic absorption spectrophotometer. Results Eluted Ti ions were detected after 24 h (pH of 2.0 and 3.0) and after 48 h (pH of 9.0). However, even after 4 weeks, eluted Ti ions were not detected in SBF solutions with pH values of 5.0 and 7.4. Ti elution was affected by immersion time, pH, acid type, mechanical stimulus, and contact with a dissimilar metal. Elution of Ti ions in a Candida albicans culture medium was observed after 72 h. Significance Elution of Ti ions in the SBF was influenced by its pH and by crevice corrosion. The results of this study elucidate the conditions that lead to the elution of Ti ions in humans, which results in implant corrosion and Ti allergy. PMID:23762461

  9. Effects of ageing on elution behaviour of nitrogenous compounds in disposed wastes from landfill sites.

    PubMed

    Nishio, Takayuki

    2014-01-01

    Comparative studies of elution and cation exchange capacity (CEC) tests were applied to aged and fresh municipal and industrial solid wastes to examine the effects of ageing on the long-term elution behaviour of nitrogen on leachate in municipal and industrial solid waste landfill sites. Nitrogen in the leachate gradually eluted as organic nitrogen, but not upon transformation of organic nitrogen to elutable inorganic nitrogen compounds in the solid waste. Ammonium in the solid waste, retained similar to its interaction with clay minerals in soil, elutes when exposed to leachate by being replaced with highly concentrated cations or loses its positive charge in high pH in the leachate, which percolates down from the upper layer of the disposed waste. The quantity of ammonium adsorbed into the aged wastes through CEC measurement process by replacement with ammonium acetate was higher than that onto the fresh wastes. That difference in quantities can serve as an index of the ability of the solid waste to withhold ammonium in the leachate that percolates down the landfill layer. Those results demonstrate that ammonification of organic nitrogen in the waste is not the crucial step of the elution of nitrogenous compounds into leachate. PMID:25145199

  10. Nonspecific native elution of proteins and mumps virus in immunoaffinity chromatography.

    PubMed

    Brgles, Marija; Sviben, Dora; Forčić, Dubravko; Halassy, Beata

    2016-05-20

    Immunoaffinity chromatography, based on the antigen-antibody recognition, enables specific purification of any antigen (protein, virus) by its antibody. The problem with immunoaffinity chromatography is the harsh elution conditions required for disrupting strong antigen-antibody interactions, such as low pH buffers, which are often deleterious for the immobilized protein and the protein to be isolated since they can also disrupt the intramolecular forces. Therefore, immunoaffinity chromatography can only be partially used for protein and virus purification. Here we report on a nonspecific elution in immunoaffinity chromatography using native conditions by elution with amino acid solution at physiological pH for which we suppose possible competing mechanism of action. Elution potential of various amino acid solutions was tested using immunoaffinity columns specific for ovalbumin and mumps virus, and protein G affinity column. Results have shown that the most successful elution solutions were those containing imidazole and arginine of high molarity. Imidazole represents aromatic residues readily found at the antigen-antibody interaction surface and arginine is most frequently found on protein surface in general. Therefore, results on their eluting power in immunoaffinity chromatography, which increases with increasing molarity, are in line with the competing mechanism of action. Virus immunoaffinity chromatography resulted in removal on nonviable virus particles, which is important for research and biotechnology purposes. In addition, amino acids are proven stabilizers for proteins and viruses making approach presented in this work a very convenient purification method.

  11. Nonspecific native elution of proteins and mumps virus in immunoaffinity chromatography.

    PubMed

    Brgles, Marija; Sviben, Dora; Forčić, Dubravko; Halassy, Beata

    2016-05-20

    Immunoaffinity chromatography, based on the antigen-antibody recognition, enables specific purification of any antigen (protein, virus) by its antibody. The problem with immunoaffinity chromatography is the harsh elution conditions required for disrupting strong antigen-antibody interactions, such as low pH buffers, which are often deleterious for the immobilized protein and the protein to be isolated since they can also disrupt the intramolecular forces. Therefore, immunoaffinity chromatography can only be partially used for protein and virus purification. Here we report on a nonspecific elution in immunoaffinity chromatography using native conditions by elution with amino acid solution at physiological pH for which we suppose possible competing mechanism of action. Elution potential of various amino acid solutions was tested using immunoaffinity columns specific for ovalbumin and mumps virus, and protein G affinity column. Results have shown that the most successful elution solutions were those containing imidazole and arginine of high molarity. Imidazole represents aromatic residues readily found at the antigen-antibody interaction surface and arginine is most frequently found on protein surface in general. Therefore, results on their eluting power in immunoaffinity chromatography, which increases with increasing molarity, are in line with the competing mechanism of action. Virus immunoaffinity chromatography resulted in removal on nonviable virus particles, which is important for research and biotechnology purposes. In addition, amino acids are proven stabilizers for proteins and viruses making approach presented in this work a very convenient purification method. PMID:27090389

  12. Effects of ageing on elution behaviour of nitrogenous compounds in disposed wastes from landfill sites.

    PubMed

    Nishio, Takayuki

    2014-01-01

    Comparative studies of elution and cation exchange capacity (CEC) tests were applied to aged and fresh municipal and industrial solid wastes to examine the effects of ageing on the long-term elution behaviour of nitrogen on leachate in municipal and industrial solid waste landfill sites. Nitrogen in the leachate gradually eluted as organic nitrogen, but not upon transformation of organic nitrogen to elutable inorganic nitrogen compounds in the solid waste. Ammonium in the solid waste, retained similar to its interaction with clay minerals in soil, elutes when exposed to leachate by being replaced with highly concentrated cations or loses its positive charge in high pH in the leachate, which percolates down from the upper layer of the disposed waste. The quantity of ammonium adsorbed into the aged wastes through CEC measurement process by replacement with ammonium acetate was higher than that onto the fresh wastes. That difference in quantities can serve as an index of the ability of the solid waste to withhold ammonium in the leachate that percolates down the landfill layer. Those results demonstrate that ammonification of organic nitrogen in the waste is not the crucial step of the elution of nitrogenous compounds into leachate.

  13. An in-vitro evaluation of three types of drug-eluting microspheres loaded with irinotecan.

    PubMed

    Pereira, Philippe L; Plotkin, Stephen; Yu, Renee; Sutter, Allison; Wu, Yue; Sommer, Christof M; Cruise, Gregory M

    2016-10-01

    To compare the mechanical and chemical properties of three commercially available microspheres loaded with irinotecan. LifePearl (200 µm), DC Bead (100-300 µm), and Tandem (100 µm) microspheres were loaded with irinotecan. For loading, elution, and stability determinations, irinotecan concentrations were quantified using validated high-performance liquid chromatography methods. In-vitro elution was performed over 24 h using a USP 4 dissolution apparatus. Diameter measurements were performed using light microscopy. Time in suspension was considered as the time required for the microspheres to vacate 1/3 of the volume. All three microsphere types rapidly loaded irinotecan, with more than 95% loading at 1 h. In-vitro elution of irinotecan was rapid for LifePearl and DC Bead microspheres, with more than 98% elution at 1 h, and delayed for Tandem microspheres, with about 70% elution at 6 h. After loading with irinotecan, the average diameter of LifePearl and DC Bead microspheres was reduced by 9 and 18%, respectively, and was unchanged for Tandem microspheres. All three microsphere types lost 4-6% of the loaded irinotecan almost immediately upon placement in contrast: water and contrast: 5% dextrose, but further losses were minimal over 2 weeks. LifePearl microspheres remained longer in suspension (392±23 s) compared with DC Bead (154±13 s, P<0.001) and Tandem (198±19 s, P<0.001) microspheres. All three microsphere types load irinotecan rapidly. LifePearl and DC Bead microspheres elute irinotecan rapidly. Elution is delayed with Tandem microspheres. LifePearl microspheres show the longest time in suspension. PMID:27416270

  14. The Influence of Irradiation Time and Layer Thickness on Elution of Triethylene Glycol Dimethacrylate from SDR® Bulk-Fill Composite.

    PubMed

    Łagocka, Ryta; Jakubowska, Katarzyna; Chlubek, Dariusz; Buczkowska-Radlińska, Jadwiga

    2016-01-01

    Objective. This study aimed to evaluate triethylene glycol dimethacrylate (TEGDMA) elution from SDR bulk-fill composite. Methods. Three groups of samples were prepared, including samples polymerized in a 4 mm layer for 20 s, in a 4 mm layer for 40 s, and in a 2 mm layer for 20 s. Elution of TEGDMA into 100% ethanol, a 75% ethanol/water solution, and distilled water was studied. The TEGDMA concentration was measured using HPLC. Results. The TEGDMA concentration decreased in the following order: 100% ethanol > 75% ethanol > distilled water. Doubling the energy delivered to the 4 mm thick sample caused decrease (p < 0.05) in TEGDMA elution to distilled water. In ethanol solutions, the energy increase had no influence on TEGDMA elution. Decreasing the sample thickness resulted in decrease (p < 0.05) in TEGDMA elution for all the solutions. Conclusions. The concentration of eluted TEGDMA and the elution time were both strongly affected by the hydrophobicity of the solvent. Doubling the energy delivered to the 4 mm thick sample did not decrease the elution of TEGDMA but did decrease the amount of the monomer available to less aggressive solvents. Elution of TEGDMA was also correlated with the exposed sample surface area. Clinical Relevance. Decreasing the SDR layer thickness decreases TEGDMA elution. PMID:27366742

  15. Precision-controlled elution of a 82Sr/82Rb generator for cardiac perfusion imaging with positron emission tomography

    NASA Astrophysics Data System (ADS)

    Klein, R.; Adler, A.; Beanlands, R. S.; de Kemp, R. A.

    2007-02-01

    A rubidium-82 (82Rb) elution system is described for use with positron emission tomography. Due to the short half-life of 82Rb (76 s), the system physics must be modelled precisely to account for transport delay and the associated activity decay and dispersion. Saline flow is switched between a 82Sr/82Rb generator and a bypass line to achieve a constant-activity elution of 82Rb. Pulse width modulation (PWM) of a solenoid valve is compared to simple threshold control as a means to simulate a proportional valve. A predictive-corrective control (PCC) algorithm is developed which produces a constant-activity elution within the constraints of long feedback delay and short elution time. The system model parameters are adjusted through a self-tuning algorithm to minimize error versus the requested time-activity profile. The system is self-calibrating with 2.5% repeatability, independent of generator activity and elution flow rate. Accurate 30 s constant-activity elutions of 10-70% of the total generator activity are achieved using both control methods. The combined PWM-PCC method provides significant improvement in precision and accuracy of the requested elution profiles. The 82Rb elution system produces accurate and reproducible constant-activity elution profiles of 82Rb activity, independent of parent 82Sr activity in the generator. More reproducible elution profiles may improve the quality of clinical and research PET perfusion studies using 82Rb.

  16. The Influence of Irradiation Time and Layer Thickness on Elution of Triethylene Glycol Dimethacrylate from SDR® Bulk-Fill Composite

    PubMed Central

    Jakubowska, Katarzyna; Chlubek, Dariusz; Buczkowska-Radlińska, Jadwiga

    2016-01-01

    Objective. This study aimed to evaluate triethylene glycol dimethacrylate (TEGDMA) elution from SDR bulk-fill composite. Methods. Three groups of samples were prepared, including samples polymerized in a 4 mm layer for 20 s, in a 4 mm layer for 40 s, and in a 2 mm layer for 20 s. Elution of TEGDMA into 100% ethanol, a 75% ethanol/water solution, and distilled water was studied. The TEGDMA concentration was measured using HPLC. Results. The TEGDMA concentration decreased in the following order: 100% ethanol > 75% ethanol > distilled water. Doubling the energy delivered to the 4 mm thick sample caused decrease (p < 0.05) in TEGDMA elution to distilled water. In ethanol solutions, the energy increase had no influence on TEGDMA elution. Decreasing the sample thickness resulted in decrease (p < 0.05) in TEGDMA elution for all the solutions. Conclusions. The concentration of eluted TEGDMA and the elution time were both strongly affected by the hydrophobicity of the solvent. Doubling the energy delivered to the 4 mm thick sample did not decrease the elution of TEGDMA but did decrease the amount of the monomer available to less aggressive solvents. Elution of TEGDMA was also correlated with the exposed sample surface area. Clinical Relevance. Decreasing the SDR layer thickness decreases TEGDMA elution. PMID:27366742

  17. Aluminum elution and precipitation in glass vials: effect of pH and buffer species.

    PubMed

    Ogawa, Toru; Miyajima, Makoto; Wakiyama, Naoki; Terada, Katsuhide

    2015-02-01

    Inorganic extractables from glass vials may cause particle formation in the drug solution. In this study, the ability of eluting Al ion from borosilicate glass vials, and tendencies of precipitation containing Al were investigated using various pHs of phosphate, citrate, acetate and histidine buffer. Through heating, all of the buffers showed that Si and Al were eluted from glass vials in ratios almost the same as the composition of borosilicate glass, and the amounts of Al and Si from various buffer solutions at pH 7 were in the following order: citrate > phosphate > acetate > histidine. In addition, during storage after heating, the Al concentration at certain pHs of phosphate and acetate buffer solution decreased, suggesting the formation of particles containing Al. In citrate buffer, Al did not decrease in spite of the high elution amount. Considering that the solubility profile of aluminum oxide and the Al eluting profile of borosilicate glass were different, it is speculated that Al ion may be forced to leach into the buffer solution according to Si elution on the surface of glass vials. When Al ions were added to the buffer solutions, phosphate, acetate and histidine buffer showed a decrease of Al concentration during storage at a neutral range of pHs, indicating the formation of particles containing Al. In conclusion, it is suggested that phosphate buffer solution has higher possibility of forming particles containing Al than other buffer solutions.

  18. Impact of ultrasonic time on hot water elution of severely biodegraded heavy oil from weathered soils.

    PubMed

    Ji, Guodong; Sui, Xin

    2010-07-15

    An ultrasound-enhanced elution system employing water at a temperature of 70 degrees C was used to remedy weathered soils contaminated with severely biodegraded heavy oil (SBHO). The effect of varying the ultrasonic irradiation time from 0 to 1800 s on the elution of SBHO and three characteristic biomarkers (C(26-34) 17alpha 25-norhopanes, C(26-28) TAS, and C(27-29) MTAS) was analyzed using GC/MS, scanning electron microscopy (SEM), and X-ray diffraction (XRD). Elution of the three biomarkers was closely related to the carbon number of the marker. C(26-34) 17alpha 25-norhopanes and C(26-28) TAS species with higher carbon numbers and C(27-29) MTAS species with lower carbon numbers were more readily eluted using sonication times of 1080-1800 s, while smaller TAS homologs were more readily eluted after sonication times of 0-360 s. SEM images of samples treated for longer periods revealed larger "bare patches" on the soil surface. The results of XRD and energy spectroscopy experiments indicated that ultrasound irradiation for 1080 s negatively affected the deposition of CaCO(3), but overall improved the mineral and chemical compositions of treated soils and removal of SBHO.

  19. DNA adsorption to and elution from silica surfaces: influence of amino acid buffers.

    PubMed

    Vandeventer, Peter E; Mejia, Jorge; Nadim, Ali; Johal, Malkiat S; Niemz, Angelika

    2013-09-19

    Solid phase extraction and purification of DNA from complex samples typically requires chaotropic salts that can inhibit downstream polymerase amplification if carried into the elution buffer. Amino acid buffers may serve as a more compatible alternative for modulating the interaction between DNA and silica surfaces. We characterized DNA binding to silica surfaces, facilitated by representative amino acid buffers, and the subsequent elution of DNA from the silica surfaces. Through bulk depletion experiments, we found that more DNA adsorbs to silica particles out of positively compared to negatively charged amino acid buffers. Additionally, the type of the silica surface greatly influences the amount of DNA adsorbed and the final elution yield. Quartz crystal microbalance experiments with dissipation monitoring (QCM-D) revealed multiphasic DNA adsorption out of stronger adsorbing conditions such as arginine, glycine, and glutamine, with DNA more rigidly bound during the early stages of the adsorption process. The DNA film adsorbed out of glutamate was more flexible and uniform throughout the adsorption process. QCM-D characterization of DNA elution from the silica surface indicates an uptake in water mass during the initial stage of DNA elution for the stronger adsorbing conditions, which suggests that for these conditions the DNA film is partly dehydrated during the prior adsorption process. Overall, several positively charged and polar neutral amino acid buffers show promise as an alternative to methods based on chaotropic salts for solid phase DNA extraction.

  20. Reduction of Solvent Effect in Reverse Phase Gradient Elution LC-ICP-MS

    SciTech Connect

    Sullivan, Patrick Allen

    2005-12-17

    %-35% (simulated) and 8%-32% (actual). Quadrupole (low resolution) and sector field (high resolution) ICP-MS instrumentation were utilized in these studies. Once an AIS pair is determined, quantification studies can be performed. First, an analysis is performed by adding both elements of the AIS pair post-column while performing the gradient elution without sample injection. A comparison of the ratio of the measured intensities to the atomic ratio of the two standards is used to determine a correction factor that can be used to account for the matrix effects caused by the mobile phase. Then, organic and/or biological molecules containing one of the two elements in the AIS pair are injected into the LC column. A gradient method is used to vary the methanol-water mixture in the mobile phase and to separate out the compounds in a given sample. A standard solution of the second ion in the AIS pair is added continuously post-column. By comparing the ratio of the measured intensities to the atomic ratio of the eluting compound and internal standard, the concentration of the injected compound can be determined.

  1. Controversies in the use & implementation of drug-eluting stent technology

    PubMed Central

    Itagaki, Brandon K.; Brar, Somjot S.

    2012-01-01

    The introduction of drug eluting stents has resulted in dramatic reductions in the rates of restenosis and the need for repeat revascularization. In the last several years, concern has been raised regarding the long-term safety of this technology, particularly in the area of late restenosis and stent thrombosis. The development of newer anti-restenotic drug coatings, biodegradable polymers and even completely bioabsorbable stents offer the potential to address these limitations. Additional questions that have recently come to the forefront include the optimal duration of dual antiplatelet therapy, the use of platelet reactivity assays and genetic testing and drug eluting stent use in the treatment of acute myocardial infarction. This article will attempt to address these and other areas of controversy in the use and implementation of drug eluting stents. PMID:23391788

  2. The elution of certain protein affinity tags with millimolar concentrations of diclofenac.

    PubMed

    Baliova, Martina; Juhasova, Anna; Jursky, Frantisek

    2015-12-01

    Diclofenac (2-[(2, 6-dichlorophenyl)amino] benzeneacetic acid) is a sparingly soluble, nonsteroidal anti-inflammatory drug therapeutically acting at low micromolar concentrations. In pH range from 8 to 11, its aqueous solubility can be increased up to 200 times by the presence of counter ions such as sodium. Our protein interaction studies revealed that a millimolar concentration of sodium diclofenac is able to elute glutathione S-transferase (GST), cellulose binding protein (CBD), and maltose binding protein (MBP) but not histidine-tagged or PDZ-tagged proteins from their affinity resins. The elution efficiency of diclofenac is comparable with the eluting agents normally used at similar concentrations. Native gel electrophoresis of sodium diclofenac-treated proteins showed that the interaction is non-covalent and non-denaturing. These results suggest that sodium diclofenac, in addition to its pharmaceutical applications, can also be exploited as a lead for the development of new proteomics reagents.

  3. Protein biomarker enrichment by biomarker antibody complex elution for immunoassay biosensing.

    PubMed

    Sabatte, Gwenola; Feitsma, Harma; Evers, Toon H; Prins, Menno W J

    2011-11-15

    It is very challenging to perform sample enrichment for protein biomarkers because proteins can easily change conformation and denature. In this paper we demonstrate protein enrichment suited for high-sensitivity integrated immuno-biosensing. The method enhances the concentration of the biomarkers and simultaneously removes matrix components that could interfere with the immunoassay. Biomarkers are captured using antibody coated magnetic particles and the biomarker antibody complexes are released by enzymatic elution. The eluted complexes are subsequently detected in a sandwich immunoassay biosensor. A scaling study of the enrichment process demonstrates an enrichment factor of 15 in buffer and plasma. We analyze the enrichment factor in terms of the three basic steps of the assay (capture, concentration, elution) and we quantify their respective efficiencies. The process is suited for integration into bio-analytical tools.

  4. Modeling smooth muscle cell proliferation of coronary artery expanded with a drug eluting stent

    NASA Astrophysics Data System (ADS)

    Lyu, Suping

    2010-03-01

    The drug eluting coronary stent is for the treatment of narrowed coronary artery. A high strength balloon is used to open the narrowed vessel and leave behind a tiny metal mesh, or stent, to mechanically prevent the vessel from re-narrowing and biologically slow down proliferation of the smooth muscle cells. However, the drug eluting stents that had better performance also more seriously prevented the healing processes of the vessels, which could cause serious thrombotic reactions. In this study, we assume the healing process is controlled by proper proliferation of smooth cells. We also assume that the inflammation reactions and mechanical traction drive the smooth muscle cells to proliferate while the drug loaded in the stents drives the processes at the opposite direction. Numerical calculation was applied to the system. The drug distribution and elution durations, inflammation reactions and mechanical traction were discussed.

  5. Alternate Methods for Eluting Cesium from Spherical Resorcinol-Formaldehyde Resin

    SciTech Connect

    Taylor, Paul Allen; Johnson, Heather Lauren

    2009-02-01

    A small-column ion exchange (SCIX) system has been proposed for removing cesium from the supernate and dissolved salt solutions in the high-level-waste tanks at the Savannah River Site (SRS). The SCIX system could use either crystalline silicotitanate (CST), an inorganic, non-regenerable sorbent, or spherical resorcinol-formaldehyde (RF), a new regenerable resin, to remove cesium from the waste solutions. The baseline method for eluting the cesium from the RF resin uses 15 bed volumes (BV) of 0.5 M nitric acid (HNO{sub 3}). The nitric acid eluate, containing the radioactive cesium, would be combined with the sludge from the waste tanks and would be converted into glass at the Defense Waste Processing Facility (DWPF) at SRS. The amount of nitric acid that would be used to elute the RF resin, using the current elution protocol, exceeds the capacity of DWPF to destroy the nitrate ions and maintain the required chemical reducing environment in the glass melt. Installing a denitration evaporator at SRS is technically feasible but would add considerable cost to the project. Alternate methods for eluting the resin have been tested, including using lower concentrations of nitric acid, other acids, and changing the flow regimes. About 4 BV of 0.5 M HNO{sub 3} are required to remove the sodium (titrate the resin) and most of the cesium from the resin, so the bulk of the acid used for the baseline elution method removes a very small quantity of cesium from the resin. A summary of the elution methods that have been tested are listed.

  6. Drug-eluting coronary stents – focus on improved patient outcomes

    PubMed Central

    Jaffery, Zehra; Prasad, Amit; Lee, John H; White, Christopher J

    2011-01-01

    The development of stent has been a major advance in the treatment of obstructive coronary artery disease since the introduction of balloon angioplasty. Subsequently, neointimal hyperplasia within the stent leading to in-stent restenosis emerged as a major obstacle in long-term success of percutaneous coronary intervention. Recent introduction of drug-eluting stents is a major breakthrough to tackle this problem. This review article summarizes stent technology, reviews progress of drug-eluting stents and discusses quality of life, patient satisfaction, and acceptability of percutaneous coronary intervention. PMID:22915977

  7. Drug-Eluting or Bare-Metal Stents for Coronary Artery Disease.

    PubMed

    Bønaa, Kaare H; Mannsverk, Jan; Wiseth, Rune; Aaberge, Lars; Myreng, Yngvar; Nygård, Ottar; Nilsen, Dennis W; Kløw, Nils-Einar; Uchto, Michael; Trovik, Thor; Bendz, Bjørn; Stavnes, Sindre; Bjørnerheim, Reidar; Larsen, Alf-Inge; Slette, Morten; Steigen, Terje; Jakobsen, Ole J; Bleie, Øyvind; Fossum, Eigil; Hanssen, Tove A; Dahl-Eriksen, Øystein; Njølstad, Inger; Rasmussen, Knut; Wilsgaard, Tom; Nordrehaug, Jan E

    2016-09-29

    Background Limited data are available on the long-term effects of contemporary drug-eluting stents versus contemporary bare-metal stents on rates of death, myocardial infarction, repeat revascularization, and stent thrombosis and on quality of life. Methods We randomly assigned 9013 patients who had stable or unstable coronary artery disease to undergo percutaneous coronary intervention (PCI) with the implantation of either contemporary drug-eluting stents or bare-metal stents. In the group receiving drug-eluting stents, 96% of the patients received either everolimus- or zotarolimus-eluting stents. The primary outcome was a composite of death from any cause and nonfatal spontaneous myocardial infarction after a median of 5 years of follow-up. Secondary outcomes included repeat revascularization, stent thrombosis, and quality of life. Results At 6 years, the rates of the primary outcome were 16.6% in the group receiving drug-eluting stents and 17.1% in the group receiving bare-metal stents (hazard ratio, 0.98; 95% confidence interval [CI], 0.88 to 1.09; P=0.66). There were no significant between-group differences in the components of the primary outcome. The 6-year rates of any repeat revascularization were 16.5% in the group receiving drug-eluting stents and 19.8% in the group receiving bare-metal stents (hazard ratio, 0.76; 95% CI, 0.69 to 0.85; P<0.001); the rates of definite stent thrombosis were 0.8% and 1.2%, respectively (P=0.0498). Quality-of-life measures did not differ significantly between the two groups. Conclusions In patients undergoing PCI, there were no significant differences between those receiving drug-eluting stents and those receiving bare-metal stents in the composite outcome of death from any cause and nonfatal spontaneous myocardial infarction. Rates of repeat revascularization were lower in the group receiving drug-eluting stents. (Funded by the Norwegian Research Council and others; NORSTENT ClinicalTrials.gov number, NCT00811772 .).

  8. Alternate Methods For Eluting Cesium From Spherical Resorcinol-Formaldehyde Resin

    SciTech Connect

    Taylor, Paul Allen; Johnson, Heather Lauren

    2009-01-01

    A Small Column Ion Exchange (SCIX) system has been proposed for removing cesium from the supernate and dissolved salt solutions in the high level waste tanks at the Savannah River Site (SRS). The SCIX system could use either crystalline silicotitanate (CST) an inorganic, non-regenerable sorbent or spherical resorcinol-formaldehyde (RF), a new regenerable resin, to remove cesium from the waste solutions. The standard method for eluting the cesium from the RF resin uses 15-20 bed volumes (BV) of 0.5 M nitric acid (HNO3). The nitric acid eluate, containing the radioactive cesium, would be combined with the sludge from the waste tanks, and would be converted into glass at the Defense Waste Processing Facility (DWPF) at SRS. The amount of nitric acid generated by the standard elution method exceeds the capacity of DWPF to destroy the nitrate ions and maintain the required chemical reducing conditions in the glass melt. Alternate methods for eluting the resin have been tested, including using lower concentrations of nitric acid, other acids, and changing the flow regimes. About 4 bed volumes of 0.5 M nitric acid are required to remove the sodium (titrate the resin) and most of the cesium from the resin, so the bulk of the acid used for the standard elution method removes a very small quantity of cesium from the resin. The resin was loaded with 9.5 g Cs/L of resin prior to elution, which is the maximum expected loading for RF resin treating the actual dissolved salt waste at SRS. For the baseline elution method, 465 g of nitrate is used per liter of resin, and >99.9999% of the cesium is removed from the resin. An alternative method that used 4 bed volumes of 0.5 M HNO3 followed by 11 bed volumes of 0.05 M HNO3, used 158 g of nitrate per liter of resin (66% less nitrate than used for the standard elution) and removed >99.998% of the cesium. A staccato flow mode using 0.5 M HNO3 (1 hr on at 1 BV/hr, followed by 3 hrs off) after the resin had been titrated using a continuous

  9. Involvement of COX-2 in nickel elution from a wire implanted subcutaneously in mice.

    PubMed

    Sato, Taiki; Kishimoto, Yu; Asakawa, Sanki; Mizuno, Natsumi; Hiratsuka, Masahiro; Hirasawa, Noriyasu

    2016-07-01

    Many types of medical alloys include nickel (Ni), and the elution of Ni ions from these materials causes toxicities and inflammation. We have previously reported that inflammation enhances Ni elution, although the molecular mechanisms underlying this effect remain unclear. In this study, we investigated how inflammatory responses enhanced Ni elution in a wire-implantation mouse model. Subcutaneous implantation of Ni wire induced the expression of cyclooxygenase-2 (COX-2) and microsomal prostaglandin E synthase-1 (mPGES-1) mRNA in the surrounding tissues. Immunostaining analysis showed that cells expressing COX-2 were mainly fibroblast-like cells 8h after implantation of a Ni wire, but were mainly infiltrated leukocytes at 24h. NiCl2 induced the expression of COX-2 mRNA in primary fibroblasts, neutrophils, RAW 264 cells, and THP-1 cells, indicating that Ni ions can induce COX-2 expression in various types of cells. The elution of Ni ions from the implanted Ni wire at 8h was reduced by dexamethasone (Dex), indomethacin (Ind), or celecoxib (Cel) treatment. Ni wire implantation induced an increase in mRNA levels for anaerobic glycolytic pathway components glucose transporter 1 (GLUT1), hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and monocarboxylate transporter 4 (MCT4); the expression of these genes was also inhibited by Dex, Ind, and Cel. In primary fibroblasts, the expression of these mRNAs and the production of lactate were induced by NiCl2 and further potentiated by PGE2. Furthermore, Ni wire-induced infiltration of inflammatory leukocytes was significantly reduced by Dex, Ind, or Cel. Depletion of neutrophils with a specific antibody caused reduction of both leukocyte infiltration and Ni elution. These results indicate that Ni ions eluted from wire induced COX-2 expression, which further promoted elution of Ni ions by increasing lactate production and leukocyte infiltration. Since COX inhibitors and Dex reduced the elution of Ni ions, these drugs may be

  10. Paclitaxel Drug-Eluting Stents in Peripheral Arterial Disease: A Health Technology Assessment

    PubMed Central

    2015-01-01

    Background Peripheral arterial disease is a condition in which atherosclerotic plaques partially or completely block blood flow to the legs. Although percutaneous transluminal angioplasty and metallic stenting have high immediate success rates in treating peripheral arterial disease, long-term patency and restenosis rates in long and complex lesions remain unsatisfactory. Objective The objective of this analysis was to evaluate the clinical effectiveness, safety, cost-effectiveness and budget impact of Zilver paclitaxel self-expanding drug-eluting stents for the treatment of de novo or restenotic lesions in above-the-knee peripheral arterial disease. Data Sources Literature searches were performed using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), and EBM Reviews. For the economic review, a search filter was applied to limit search results to economics-related literature. Data sources for the budget impact analysis included expert opinion, published literature, and Ontario administrative data. Review Methods Systematic reviews, meta-analyses, randomized controlled trials, and observational studies were included in the clinical effectiveness review, and full economic evaluations were included in the economic literature review. Studies were included if they examined the effect of Zilver paclitaxel drug-eluting stents in de novo or restenotic lesions in above-the-knee arteries. For the budget impact analysis, 3 scenarios were constructed based on different assumptions. Results One randomized controlled trial reported a significantly higher patency rate with Zilver paclitaxel drug-eluting stents for lesions ≤ 14 cm than with angioplasty or bare metal stents. One observational study showed no difference in patency rates between Zilver paclitaxel drug-eluting stents and paclitaxel drug-coated balloons. Zilver paclitaxel drug-eluting stents were associated with

  11. Vancomycin-eluting niosomes: a new approach to the inhibition of staphylococcal biofilm on abiotic surfaces.

    PubMed

    Barakat, Heba S; Kassem, Mervat A; El-Khordagui, Labiba K; Khalafallah, Nawal M

    2014-10-01

    A new vancomycin (VCM)-eluting mixed bilayer niosome formulation was evaluated for the control of staphylococcal colonization and biofilm formation on abiotic surfaces, a niosome application not explored to date. Cosurfactant niosomes were prepared using a Span 60/Tween 40/cholesterol blend (1: 1: 2). Tween 40, a polyethoxylated amphiphile, was included to enhance VCM entrapment and confer niosomal surface properties precluding bacterial adhesion. VCM-eluting niosomes showed good quality attributes including relatively high entrapment efficiency (∼50%), association of Tween 40 with vesicles in a constant proportion (∼87%), biphasic release profile suitable for inhibiting early bacterial colonization, and long-term stability at 4°C for a 12-month study period. Niosomes significantly enhanced VCM activity against planktonic bacteria of nine staphylococcal strains. Using microtiter plates as abiotic surface, VCM-eluting niosomes proved superior to VCM in inhibiting biofilm formation, eradicating surface-borne biofilms, inhibiting biofilm growth, and interfering with biofilm induction by VCM subminimal inhibitory concentrations. Data suggest dual functionality of cosurfactant VCM-eluting niosomes as passive colonization inhibiting barrier and active antimicrobial-controlled delivery system, two functions recognized in infection control of abiotic surfaces and medical devices.

  12. Gene Expression Pattern after Insertion of Dexamethasone-Eluting Electrode into the Guinea Pig Cochlea

    PubMed Central

    Mugridge, Kenneth; Oguchi, Tomohiro; Hashimoto, Shigenari; Suzuki, Nobuyoshi; Iwasaki, Satoshi; Jolly, Claude; Usami, Shin-ichi

    2014-01-01

    A cochlear implant is an indispensable apparatus for a profound hearing loss patient. But insertion of the electrode entails a great deal of stress to the cochlea, and may cause irreversible damage to hair cells and related nerve structure. Although damage prevention effects of dexamethasone have been reported, long-term administration is difficult. In this study, we used a dexamethasone-eluting electrode in the guinea pig cochlea, and compared the gene expression after 7 days insertion with that of a normal electrode and non-surgically treated control by microarray. 40 genes were up-regulated 2-fold or more in the normal electrode group compared to the non-surgically treated group. Most of the up-regulated genes were associated with immune response and inflammation. In the dexamethasone-eluting group, compared to the normal electrode group, 7 of the 40 genes were further up-regulated, while 12 of them were down-regulated and there was a tendency to return to the non-surgical condition. 9 genes were down-regulated 2-fold or less with normal electrode insertion, and 4 of the 9 tended to return to the non-surgical condition in the dexamethasone-eluting group. These genes are certainly involved in the maintenance of the physiological functions of the cochlea. Our results indicate that the dexamethasone-eluting electrode will have an effect on the normalization of homeostasis in the cochlea. PMID:25329543

  13. AN ALTERNATIVE ELUENT TO BEEF EXTRACT FOR ELUTING POLIOVIRUS FROM ELECTROPOSITIVE FILTERS

    EPA Science Inventory

    Traditional methods for enteric virus removal from waters involve filtering the water through a positively charged filter followed by elution with beef extract, second step concentration by flocculation, and assay in cell culture. Two of the problems associated with this method ...

  14. Highly porous drug-eluting structures: from wound dressings to stents and scaffolds for tissue regeneration.

    PubMed

    Elsner, Jonathan J; Kraitzer, Amir; Grinberg, Orly; Zilberman, Meital

    2012-01-01

    For many biomedical applications, there is need for porous implant materials. The current article focuses on a method for preparation of drug-eluting porous structures for various biomedical applications, based on freeze drying of inverted emulsions. This fabrication process enables the incorporation of any drug, to obtain an "active implant" that releases drugs to the surrounding tissue in a controlled desired manner. Examples for porous implants based on this technique are antibiotic-eluting mesh/matrix structures used for wound healing applications, antiproliferative drug-eluting composite fibers for stent applications and local cancer treatment, and protein-eluting films for tissue regeneration applications. In the current review we focus on these systems. We show that the release profiles of both types of drugs, water-soluble and water-insoluble, are affected by the emulsion's formulation parameters. The former's release profile is affected mainly through the emulsion stability and the resulting porous microstructure, whereas the latter's release mechanism occurs via water uptake and degradation of the host polymer. Hence, appropriate selection of the formulation parameters enables to obtain desired controllable release profile of any bioactive agent, water-soluble or water-insoluble, and also fit its physical properties to the application.

  15. Effectiveness of sirolimus-eluting stent implantation for the treatment of coronary artery disease in octogenarians.

    PubMed

    Vijayakumar, Maniyal; Lemos, Pedro A; Hoye, Angela; Ong, Andrew T L; Aoki, Jiro; Granillo, Gaston Rodriguez; McFadden, Eugene P; Sianos, Georgios; Hofma, Sjoerd H; Smits, Pieter C; van der Giessen, Willem J; de Feyter, Pim; van Domburg, Ron T; Cummins, Paul A; Serruys, Patrick W

    2004-10-01

    Sirolimus-eluting stent (SES) implantation has been shown to reduce repeat revascularization in various randomized trials. The present study evaluated the outcomes after SES implantation in 46 octogenarian patients. SES implantation in octogenarians appears to be feasible and is associated with very small subsequent need for repeat target vessel revascularization at 1 year.

  16. Percutaneous radial intervention for complex bilateral renal artery stenosis using paclitaxel eluting stents.

    PubMed

    Granillo, Gastón A Rodriguez; van Dijk, Lukas C; McFadden, Eugène P; Serruys, Patrick W

    2005-01-01

    Techniques used in the coronary circulation may be useful in peripheral intervention. We report a case of bilateral renal artery stenosis treated via a radial approach by direct stenting with distal protection at a right ostial lesion and modified crush stenting at a left renal bifurcation lesion using paclitaxel-eluting stents.

  17. Fiscal year 1996 laboratory scale studies of cesium elution in tank 8D-1

    SciTech Connect

    Russell, R.L.; Patello, G.K.; Sills, J.A.

    1996-09-01

    This report details work performed as part of the West Valley Support Project (WVSP) by Pacific Northwest National Laboratory (PNNL). This work is intended to support residual waste removal during high-level waste (HLW) tank stabilization activities to be performed by the West valley Demonstration Project (WVDP). The HLW originated from a now inactive commercial nuclear fuel-reprocessing plant at West Valley, New York. It is stored in a carbon-steel tank designated 8D-2. Cesium-loaded zeolite was generated by a supernatant decontamination process involving ion exchange. The exchange columns and the spent zeolite are stored in a carbon-steel tank designated 8D-1. During the vitrification phase of the WVDP waste remediation, and estimated 95 percent of the zeolite will be transferred from tank 8D-1 to tank 8D- 2. The remaining cesium-loaded zeolite will require treatment to remove the highly radioactive cesium. This report summarizes the findings of laboratory experiments. The primary objectives of these experiments were: to refine the optimum process conditions for use of oxalic acid to elute cesium from zeolite; minimize iron dissolution during cesium elution; investigation of the effect of neutralization on cesium elution; determination of effects of zeolite particle size on cesium elution; and determine if aluminum can be used as an indicator for cesium in solution.

  18. 40 CFR 799.6784 - TSCA water solubility: Column elution method; shake flask method.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... temperature. (iii) Flask method: Test procedure. The quantity of material necessary to saturate the desired... source material used in developing this TSCA test guideline is the Office of Pollution Prevention... tested and the test temperatures; it ranges from 0.05 to 0.34 for the column elution method, and from...

  19. Elution of zinc in dust discharged from electric arc furnace in carbonic acid solution

    NASA Astrophysics Data System (ADS)

    Yokoyama, S.; Sasaki, T.; Sasano, J.; Izaki, M.

    2012-03-01

    The dust discharged from an electric arc furnace (EAF) is a valuable resource of zinc. As a fundamental study of extraction of zinc, iron and chlorine in the EAF dust, the elution behavior of them in carbonic acid solution was studied. The influence of the weight of the EAF dust on the elution behavior was examined in this study. Experiment was carried out putting the EAF dust from 1 g to 200 g in weight into 1 L of water that was introduced by CO2. Generally, the pH in the aqueous solution increased with an increase in weight of the additive EAF dust. Maximums of the eluted concentrations of zinc and chloride ion increased with an increase in the weight of the additive EAF dust whereas the extraction ratios of both of them decreased with an increase in the weight of the additive EAF dust. Iron in the EAF dust remained in the dust without elution. The limit of extraction of zinc from the EAF dust to water was given by the solubilities of ZnFe2O4 and ZnO expressed by eq. (6) and eq. (9) respectively.

  20. Elution behavior of insulin on high-performance size exclusion chromatography at neutral pH.

    PubMed

    Tantipolphan, Ruedeeporn; Romeijn, Stefan; Engelsman, John den; Torosantucci, Riccardo; Rasmussen, Tue; Jiskoot, Wim

    2010-06-01

    The pharmacopoeia protocol for HP-SEC of insulin, using an acidic non-physiological eluent, does not represent insulin's association state in the formulation. This study aimed to evaluate insulin's elution behavior in HP-SEC in a "physiological" (aqueous, neutral pH) eluent, using on-line UV absorption and multi-angle laser light scattering detection. The effect of insulin concentration and association state in the formulation (monitored by circular dichroism) and eluent composition (zinc ion, arginine) on its elution behavior was assessed. We showed that the elution behavior of insulin in "physiological" HP-SEC is affected by both dynamic association-dissociation of insulin molecules and insulin-column interactions. Insulin molecules re-equilibrated in the HP-SEC eluent, making its elution behavior practically insensitive to the association state of insulin in the formulation. Zinc ions in the eluent promoted association of insulin to hexamers, whereas arginine overruled the effect of zinc ions and induced on-column dissociation of insulin to dimers and monomers. Combined results from "physiological" and compendial HP-SEC were shown to provide a better view of the aggregation state of heat-stressed insulin than either of the single methods. The insights obtained with this study are crucial for a proper evaluation of HP-SEC data of insulin. PMID:20129751

  1. Endovascular treatment of in-stent restenosis using excimer laser angioplasty and drug eluting balloons.

    PubMed

    Van Den Berg, J C; Pedrotti, M; Canevascini, R; Chimchila Chevili, S; Giovannacci, L; Rosso, R

    2012-04-01

    In-stent restenosis after endovascular treatment of stenotic and occlusive disease of the infrainguinal arteries is still a clinical challenge. In this paper an overview of the current status of drug-eluting balloon technology and results of clinical trials with drug-eluting balloon angioplasty is given. Furthermore a case series of 10 patients with in-stent restenosis that were treated with excimer laser angioplasty and drug eluting balloons is described. In this case series the mean lesion length treated was 115 mm, and the mean time to occurrence of restenosis after initial treatment was 7.2 months. At a mean follow-up (of all patients) of 7.6 months no target vessel revascularization was seen. In 7 patients that had Duplex and/or angiographic control (mean follow-up 7 months) no signs of neointimal hyperplasia were demonstrated. These short-term data compare favorable to results obtained with standard balloon angioplasty and cutting-balloon angioplasty. Long-term follow-up is necessary to define the role of combined excimer laser and drug-eluting balloon angioplasty in the treatment of in-stent restenosis further.

  2. Small-Column Cesium Ion Exchange Elution Testing of Spherical Resorcinol-Formaldehyde

    SciTech Connect

    Brown, Garrett N.; Russell, Renee L.; Peterson, Reid A.

    2011-10-21

    This report summarizes the work performed to evaluate multiple, cesium loading, and elution cycles for small columns containing SRF resin using a simple, high-level waste (HLW) simulant. Cesium ion exchange loading and elution curves were generated for a nominal 5 M Na, 2.4E-05 M Cs, 0.115 M Al loading solution traced with 134Cs followed by elution with variable HNO3 (0.02, 0.07, 0.15, 0.23, and 0.28 M) containing variable CsNO3 (5.0E-09, 5.0E-08, and 5.0E-07 M) and traced with 137Cs. The ion exchange system consisted of a pump, tubing, process solutions, and a single, small ({approx}15.7 mL) bed of SRF resin with a water-jacketed column for temperature-control. The columns were loaded with approximately 250 bed volumes (BVs) of feed solution at 45 C and at 1.5 to 12 BV per hour (0.15 to 1.2 cm/min). The columns were then eluted with 29+ BVs of HNO3 processed at 25 C and at 1.4 BV/h. The two independent tracers allowed analysis of the on-column cesium interaction between the loading and elution solutions. The objective of these tests was to improve the correlation between the spent resin cesium content and cesium leached out of the resin in subsequent loading cycles (cesium leakage) to help establish acid strength and purity requirements.

  3. Modeling the elution of organic chemicals from a melting homogeneous snow pack.

    PubMed

    Meyer, Torsten; Wania, Frank

    2011-06-01

    Organic chemicals are often released in peak concentrations from melting snow packs. A simple, mechanistic snowmelt model was developed to simulate and predict the elution of organic substances from melting, homogeneous snow, as influenced by chemical properties and snow pack characteristics. The model calculates stepwise the chemical transport along with the melt water flow in a multi-layered snow pack, based on chemical equilibrium partitioning between the individual bulk snow phases. The model succeeds in reproducing the elution behavior of several organic contaminants observed in previously conducted cold room experiments. The model aided in identifying four different types of enrichment of organic substances during snowmelt. Water soluble substances experience peak releases early during a melt period (type 1), whereas chemicals that strongly sorb to particulate matter (PM) or snow grain surfaces elute at the end of melting (type 2). Substances that are somewhat water soluble and at the same time have a high affinity for snow grain surfaces may exhibit increasing concentrations in the melt water (type 3). Finally, elution sequences involving peak loads both at the beginning and the end of melting are simulated for chemicals that are partially dissolved in the aqueous melt water phase and partially sorbed to PM (type 4). The extent of type 1 enrichment mainly depends on the snow depth, whereby deeper snow generates more pronounced concentration peaks. PM influences the elution behavior of organic chemicals strongly because of the very large natural variability in the type and amount of particles present in snow. Urban and road-side snow rich in PM can generate type 2 concentration peaks at the end of the melt period for even relatively water soluble substances. From a clean, melting snow pack typical for remote regions, even fairly hydrophobic chemicals can be released in type 1 mode while being almost completely dissolved in the aqueous melt water phase. The

  4. Modeling the elution of organic chemicals from a melting homogeneous snow pack.

    PubMed

    Meyer, Torsten; Wania, Frank

    2011-06-01

    Organic chemicals are often released in peak concentrations from melting snow packs. A simple, mechanistic snowmelt model was developed to simulate and predict the elution of organic substances from melting, homogeneous snow, as influenced by chemical properties and snow pack characteristics. The model calculates stepwise the chemical transport along with the melt water flow in a multi-layered snow pack, based on chemical equilibrium partitioning between the individual bulk snow phases. The model succeeds in reproducing the elution behavior of several organic contaminants observed in previously conducted cold room experiments. The model aided in identifying four different types of enrichment of organic substances during snowmelt. Water soluble substances experience peak releases early during a melt period (type 1), whereas chemicals that strongly sorb to particulate matter (PM) or snow grain surfaces elute at the end of melting (type 2). Substances that are somewhat water soluble and at the same time have a high affinity for snow grain surfaces may exhibit increasing concentrations in the melt water (type 3). Finally, elution sequences involving peak loads both at the beginning and the end of melting are simulated for chemicals that are partially dissolved in the aqueous melt water phase and partially sorbed to PM (type 4). The extent of type 1 enrichment mainly depends on the snow depth, whereby deeper snow generates more pronounced concentration peaks. PM influences the elution behavior of organic chemicals strongly because of the very large natural variability in the type and amount of particles present in snow. Urban and road-side snow rich in PM can generate type 2 concentration peaks at the end of the melt period for even relatively water soluble substances. From a clean, melting snow pack typical for remote regions, even fairly hydrophobic chemicals can be released in type 1 mode while being almost completely dissolved in the aqueous melt water phase. The

  5. The rapid identification of elution conditions for therapeutic antibodies from cation-exchange chromatography resins using high-throughput screening.

    PubMed

    McDonald, Paul; Tran, Benjamin; Williams, Christopher R; Wong, Marc; Zhao, Ti; Kelley, Brian D; Lester, Philip

    2016-02-12

    Cation-exchange chromatography is widely used in the purification of therapeutic antibodies, wherein parameters such as elution pH and counterion concentration require optimization for individual antibodies across different chromatography resins. With a growing number of antibodies in clinical trials and the pressure to expedite process development, we developed and automated a high-throughput batch-binding screen to more efficiently optimize elution conditions for cation-exchange chromatography resins. The screen maps the binding behavior of antibodies and impurities as a function of pH and counterion concentration in terms of a partition coefficient (Kp). Using this approach, the binding behavior of a library of antibodies was assessed on Poros 50HS and SP Sepharose Fast Flow resins. The diversity in binding behavior between antibodies and across resins translated to the requirement of a variable counterion concentration to elute each antibody. This requirement can be met through the use of a gradient elution. However, a gradient of increasing counterion concentration spans the transition from binding to non-binding for impurities as well as the antibody, resulting in the elution of impurities within the antibody elution peak. Step elution conditions that selectively elute the antibody while retaining impurities on the resin can now be rapidly identified using our high-throughput approach. We demonstrate that by correlating antibody Kp to elution pool volume and yield on packed-bed columns and through the calculation of a separation factor, we can efficiently optimize step elution conditions that maximize impurity clearance and yield for each antibody. PMID:26803905

  6. Labview utilities

    2011-09-30

    The software package provides several utilities written in LabView. These utilities don't form independent programs, but rather can be used as a library or controls in other labview programs. The utilities include several new controls (xcontrols), VIs for input and output routines, as well as other 'helper'-functions not provided in the standard LabView environment.

  7. Influence of Sterilization and Storage Period on Elution of Polyvinylpyrrolidone from Wet-Type Polysulfone Membrane Dialyzers.

    PubMed

    Miyata, Masahiro; Konishi, Shuji; Shimamoto, Yoshimasa; Kamada, Aki; Umimoto, Koichi

    2015-01-01

    The objectives of this study were to investigate the influence of the sterilization and storage period on elution of polyvinylpyrrolidone (PVP) from wet-type polysulfone (PSu) membrane dialyzers. APS-15SA (APS) dialyzers sterilized by gamma-radiation and RENAK PS-1.6 (RENAK) dialyzers sterilized by autoclaving were compared in this study. Each dialyzer was washed with physiological saline and the amount of PVP eluted from the PSu membrane was measured. Then, experimental use of each dialyzer was performed by circulating physiological saline for 4 hours, after which the PVP eluted from the PSu membrane was measured. As the results, the amount of PVP eluted by washing was positively correlated with the storage period for both dialyzers (APS: rs = 0.958; RENAK: rs = 0.952). In the experimental circuit, the amount of PVP eluted from the RENAK dialyzer was positively correlated with the storage period (rs = 0.810), whereas the amount of PVP eluted from the APS dialyzer was negatively correlated with the storage period (rs = -0.833). We found that the amount of PVP eluted from PSu membrane is quite different by the sterilization and storage period of dialyzers. PMID:25851313

  8. Influence of Sterilization and Storage Period on Elution of Polyvinylpyrrolidone from Wet-Type Polysulfone Membrane Dialyzers.

    PubMed

    Miyata, Masahiro; Konishi, Shuji; Shimamoto, Yoshimasa; Kamada, Aki; Umimoto, Koichi

    2015-01-01

    The objectives of this study were to investigate the influence of the sterilization and storage period on elution of polyvinylpyrrolidone (PVP) from wet-type polysulfone (PSu) membrane dialyzers. APS-15SA (APS) dialyzers sterilized by gamma-radiation and RENAK PS-1.6 (RENAK) dialyzers sterilized by autoclaving were compared in this study. Each dialyzer was washed with physiological saline and the amount of PVP eluted from the PSu membrane was measured. Then, experimental use of each dialyzer was performed by circulating physiological saline for 4 hours, after which the PVP eluted from the PSu membrane was measured. As the results, the amount of PVP eluted by washing was positively correlated with the storage period for both dialyzers (APS: rs = 0.958; RENAK: rs = 0.952). In the experimental circuit, the amount of PVP eluted from the RENAK dialyzer was positively correlated with the storage period (rs = 0.810), whereas the amount of PVP eluted from the APS dialyzer was negatively correlated with the storage period (rs = -0.833). We found that the amount of PVP eluted from PSu membrane is quite different by the sterilization and storage period of dialyzers.

  9. The Ultimaster Biodegradable-Polymer Sirolimus-Eluting Stent: An Updated Review of Clinical Evidence

    PubMed Central

    Chisari, Alberto; Pistritto, Anna Maria; Piccolo, Raffaele; La Manna, Alessio; Danzi, Gian Battista

    2016-01-01

    The Ultimaster coronary stent system (Terumo Corporation, Tokyo, Japan) represents a new iteration in drug-eluting stent (DES) technology that has recently received the Conformité Européenne (CE) mark approval for clinical use. The Ultimaster is a thin-strut, cobalt chromium, biodegradable-polymer, sirolimus-eluting coronary stent. The high elasticity of the biodegradable-polymer (PDLLA-PCL) and the abluminal gradient coating technology are additional novel features of this coronary device. The Ultimaster DES has undergone extensive clinical evaluation in two studies: The CENTURY I and II trials. Results from these two landmark studies suggested an excellent efficacy and safety profile of the Ultimaster DES across several lesion and patient subsets, with similar clinical outcomes to contemporary, new-generation DES. The aim of this review is to summarize the rationale behind this novel DES technology and to provide an update of available evidence about the clinical performance of the Ultimaster DES. PMID:27608017

  10. Everolimus-eluting stent platforms in percutaneous coronary intervention: comparative effectiveness and outcomes

    PubMed Central

    Panoulas, Vasileios F; Mastoris, Ioannis; Konstantinou, Klio; Tespili, Maurizio; Ielasi, Alfonso

    2015-01-01

    Despite the remarkable benefits obtained following the introduction of the first-generation drug-eluting stent (DES), concerns were raised over its long-term safety, particularly with regard to very late (beyond 1 year) stent thrombosis. Newer-generation DESs have been developed to overcome this limitation using novel stent platforms, new drugs, more biocompatible durable polymers, and bioabsorbable polymers or backbones. To date, new-generation DESs have virtually replaced the use of first-generation DESs worldwide. In this review article, we discuss in detail the design, pharmacology, and mechanism of action of the newer-generation permanent and bioresorbable everolimus-eluting platforms. Furthermore, we present and evaluate the current evidence on the performance and safety of these devices compared to those of other available stent platforms. PMID:26244031

  11. The Ultimaster Biodegradable-Polymer Sirolimus-Eluting Stent: An Updated Review of Clinical Evidence.

    PubMed

    Chisari, Alberto; Pistritto, Anna Maria; Piccolo, Raffaele; La Manna, Alessio; Danzi, Gian Battista

    2016-01-01

    The Ultimaster coronary stent system (Terumo Corporation, Tokyo, Japan) represents a new iteration in drug-eluting stent (DES) technology that has recently received the Conformité Européenne (CE) mark approval for clinical use. The Ultimaster is a thin-strut, cobalt chromium, biodegradable-polymer, sirolimus-eluting coronary stent. The high elasticity of the biodegradable-polymer (PDLLA-PCL) and the abluminal gradient coating technology are additional novel features of this coronary device. The Ultimaster DES has undergone extensive clinical evaluation in two studies: The CENTURY I and II trials. Results from these two landmark studies suggested an excellent efficacy and safety profile of the Ultimaster DES across several lesion and patient subsets, with similar clinical outcomes to contemporary, new-generation DES. The aim of this review is to summarize the rationale behind this novel DES technology and to provide an update of available evidence about the clinical performance of the Ultimaster DES. PMID:27608017

  12. Advantages of novel BioMimeTM Sirolimus Eluting Coronary Stent system. Moving towards biomimicry.

    PubMed

    Upendra, K; Sanjeev, B

    2012-02-01

    Since the first reported use of percutaneous transluminal coronary angioplasty (PTCA), advancements in interventional cardiology arena have been fast paced. Within the last ten years, these developments have been exponential. Developers & clinicians are fast adapting from the learning curve awarded by the time course of DES evolution. In that light BioMimeTM Sirolimus Eluting Coronary Stent comes as a fresh thought in taking stents towards a biomimicry concept. The stent is built on an ultra-low strut thickness (65 µm) cobalt chromium stent platform, using an intelligent hybrid of close and open cells allowing for morphology mediated expansion, employs a well known anti-proliferative - Sirolimus that elutes from a biodegradable co-polymer formulation in 30 days and ensures high coating integrity and low coating thickness of 2 µm. The resultant stent demonstrates almost 100% endothelialization at 30 days in preclinical model and zero percent MACE >18 months in the primary efficacy and safety clinical study.

  13. Application of cyclodextrin-based eluents in hydrophobic charge-induction chromatography: elution of antibody at neutral pH.

    PubMed

    Ren, Jun; Yao, Peng; Cao, Yaming; Cao, Jian; Zhang, Lijun; Wang, Yuanqiang; Jia, Lingyun

    2014-07-25

    Hydrophobic charge-induction chromatography (HCIC) has emerged as a useful addition to Protein A chromatography for antibody purification due to its remarkable merits in cost and stability. However, the instability of antibody during acidic elution, which may cause inactivation and aggregation, is still a major concern for the efficiency of this method. The aim of this study is to develop a new strategy of competitive elution with inclusion complexes in HCIC, and to apply it to antibody elution under neutral pH conditions. Interactions between 4-mercaptoethylpyridine (MEP), a typical ligand of HCIC, and four different types of cyclodextrins (CDs) were investigated by molecular docking; immunoglobulin G (IgG) elution capacities of CDs were characterized on MEP-based HCIC mediums. The results demonstrated the general effectiveness of CD-based eluents for HCIC. This type of displacement eluents could allow an efficient elution of bound antibody over a broad range of pH and ion strength. With 15 mM β-CD, elution of human IgG was achieved at physiological pH, with an average IgG recovery of 87%. When this elution strategy was used to separate antibody directly from human serum, substantial elution of bound IgG could be obtained at pH 7.4, with product purity comparable to traditional method with an acidic buffer. We expect such method can be of special interest in developing HCIC elution strategy for the proteins like antibody that are sensitive to acidic conditions.

  14. Extraction and chromatographic elution behavior of endohedral metallofullerenes: Inferences regarding effective dipole moments

    SciTech Connect

    Fuchs, D.; Rietschel, H.; Michel, R.H.; Fischer, A.; Weis, P.; Kappes, M.M.

    1996-01-11

    Chromatographic retention relationships between Ce-, Gd-, La-, and Y- containing endohedral metallofullerenes and a [2-(1-pyrenyl)ethyl]silyl-silica stationary phase were studied using toluene as eluent. Measurements are discussed in comparison to those of empty fullerenes. Both the extraction and chromatographic elution behaviour of the metallofullerenes reflect their polar nature and allow inferences regarding the presence of a dipole moment in M@C{sub 82}. 55 refs., 4 figs.

  15. Study of restenosis in drug eluting stents: new insights from greyscale intravascular ultrasound and virtual histology.

    PubMed

    Garcia-Garcia, Hector M; Shen, Zhujun; Piazza, Nicolo

    2009-05-01

    In current cardiology practice, many patients undergo secondary revascularisation due to reduced long-term vein graft patency or in-stent restenosis. In this report, we describe causes of drug-eluting stent restenosis identifiable by intravascular ultrasound imaging (IVUS) and variables related to restenosis used for reporting greyscale IVUS. In addition, IVUS findings in bypass grafts and the long-term results after stent implantation are provided. Finally, the usefulness of IVUS virtual histology for the study of restenosis is described.

  16. Severe Complication After a Doxorubicin-Eluting-Bead Embolization: Surgical Management and Pathological Findings

    SciTech Connect

    Lesevic, Veiba Marzano, Ettore; Greget, Michel; Rosso, Edoardo Bachellier, Philippe Pessaux, Patrick

    2011-02-15

    Doxorubicin-eluting-bead embolization (DEB) is considered a safe and efficient treatment of hepatocellular carcinoma (HCC) with a low complication rate and an increased tumor response compared with conventional transarterial chemoembolization. We describe a case of a 69-year-old patient who underwent DEB for HCC and who developed a liver abscess requiring urgent left liver lobectomy. Despite this severe complication, efficacy of DEB embolization was histologically proved as a large ischemic zone with complete tumor necrosis.

  17. Hepatic Arterial Chemoembolization Using Drug-Eluting Beads in Gastrointestinal Neuroendocrine Tumor Metastatic to the Liver

    SciTech Connect

    Gaur, Shantanu K.; Friese, Jeremy L.; Sadow, Cheryl A.; Ayyagari, Rajasekhara; Binkert, Christoph A.; Schenker, Matthew P.; Kulke, Matthew; Baum, Richard

    2011-06-15

    Purpose: This study was designed to evaluate short (<3 months) and intermediate-term (>3 months) follow-up in patients with metastatic neuroendocrine tumor to the liver who underwent hepatic arterial chemoembolization with drug-eluting beads at a single institution. Methods: Institutional review board approval was obtained for this retrospective review. All patients who were treated with 100-300 or 300-500 {mu}m drug-eluting LC Beads (Biocompatibles, UK) preloaded with doxorubicin (range, 50-100 mg) for GI neuroendocrine tumor metastatic to the liver from June 2004 to June 2009 were included. CT and MRI were evaluated for progression using Response Evaluation Criteria In Solid Tumors (RECIST) or European Association for the Study of the Liver (EASL) criteria. Short-term (<3 months) and intermediate-term (>3 months) imaging response was determined and Kaplan-Meier survival curves were plotted. Results: Thirty-eight drug-eluting bead chemoembolization procedures were performed on 32 hepatic lobes, comprising 21 treatment cycles in 18 patients. All procedures were technically successful with two major complications (biliary injuries). At short-term follow-up (<3 months), 22 of 38 (58%) procedures and 10 of 21 (48%) treatment cycles produced an objective response (OR) with the remainder having stable disease (SD). At intermediate-term follow-up (mean, 445 days; range, 163-1247), 17 of 26 (65%) procedures and 8 of 14 (57%) treatment cycles produced an OR. Probability of progressing was approximately 52% at 1 year with a median time to progression of 419 days. Conclusions: Drug-eluting bead chemoembolization is a reasonable alternative to hepatic arterial embolization and chemoembolization for the treatment of metastatic neuroendocrine tumor to the liver.

  18. Everolimus-induced Pneumonitis after Drug-eluting Stent Implantation: A Case Report

    SciTech Connect

    Sakamoto, Susumu Kikuchi, Naoshi; Ichikawa, Atsuo; Sano, Go; Satoh, Keita; Sugino, Keishi; Isobe, Kazutoshi; Takai, Yujiro; Shibuya, Kazutoshi; Homma, Sakae

    2013-08-01

    Despite the wide use of everolimus as an antineoplastic coating agent for coronary stents to reduce the rate of restenosis, little is known about the health hazards of everolimus-eluting stents (EES). We describe a case of pneumonitis that developed 2 months after EES implantation for angina. Lung pathology demonstrated an organizing pneumonia pattern that responded to corticosteroid therapy. Although the efficacy of EES for ischemic heart disease is well established, EES carries a risk of pneumonitis.

  19. Modeling of dual gradient elution in ion exchange and mixed-mode chromatography.

    PubMed

    Lee, Yi Feng; Schmidt, Michael; Graalfs, Heiner; Hafner, Mathias; Frech, Christian

    2015-10-23

    Protein retention using dual gradient elution in ion exchange- and mixed-mode chromatography can be modeled using the combination of a modified Yamamoto's LGE model and a conversion term to correlate the elution salt concentration and pH at any given gradient slope. Incorporation of the pH dependence of the binding charges into the model also provides some insights on the dual effects of salt and pH in protein-ligand interaction. The fitted thermodynamic parameters (ΔGP(0)/RT, ΔGS(0)/RT, number of charged amino acids involved in binding) of the dual gradient elution data using lysozyme and mAbs on SP Sepharose(®) FF, Eshmuno(®) HCX, and Capto(®) MMC ImpRes were consistent to the results of mono gradient data. This gives rise to an approach to perform thermodynamic modeling of protein retention in ion exchange- and mixed-mode chromatography by combining both salt and pH gradient into a single run of dual gradient elution which will increase time and cost efficiency. The dual gradients used in this study encompassed a wide range of pH (4-8) and NaCl concentrations (0-1M). Curve fits showed that ΔGP(0)/RT is protein type and ligand dependent. ΔGS(0)/RT is strongly dependent on the stationary phase but not the protein. For mAb04 on mixed-mode resin Capto(®) MMC, ΔGS(0)/RT is 5-6 times higher than the result reported for the same protein on cation exchanger Fractogel(®) EMD SO3(-) (S).

  20. In vitro hemocompatibility and cytocompatibility of dexamethasone-eluting PLGA stent coatings

    NASA Astrophysics Data System (ADS)

    Zhang, Jiang; Liu, Yang; Luo, Rifang; Chen, Si; Li, Xin; Yuan, Shuheng; Wang, Jin; Huang, Nan

    2015-02-01

    Drug-eluting stents (DESs) have been an important breakthrough for interventional cardiology applications since 2002. Though successful in reducing restenosis, some adverse clinical problems still emerged, which were mostly caused by the bare-metal stents and non-biodegradable polymer coatings, associated with the delayed endothelialization process. In this study, dexamethasone-loaded poly (lactic-co-glycolic acid) (PLGA) coatings were developed to explore the potential application of dexamethasone-eluting stents. Dexamethasone-eluting PLGA stents were prepared using ultrasonic atomization spray method. For other tests like stability and cytocompatibility and hemocompatibility tests, dexamethasone loaded coatings were deposited on 316L SS wafers. Fourier transform-infrared spectroscopy (FT-IR) results demonstrated that there was no chemical reaction between PLGA and dexamethasone. The balloon expansion experiment and surface morphology observation suggested that the stent coatings were smooth and uniform, and could also withstand the compressive and tensile strains imparted without cracking after stent expansion. The drug release behavior in vitro indicated that dexamethasone existed burst release within 1 day, but it presented linear release characteristics after 6 days. In vitro platelets adhesion, activation test and APTT test were also done, which showed that after blending dexamethasone into PLGA, the hemocompatibility was improved. Besides, dexamethasone and dexamethasone-loaded PLGA coatings could significantly inhibit the attachment and proliferation of smooth muscle cells.

  1. Elution kinetics, antimicrobial activity, and mechanical properties of 11 different antibiotic loaded acrylic bone cement.

    PubMed

    Gálvez-López, Ruben; Peña-Monje, Alejandro; Antelo-Lorenzo, Ramón; Guardia-Olmedo, Juan; Moliz, Juan; Hernández-Quero, José; Parra-Ruiz, Jorge

    2014-01-01

    Antibiotic-loaded acrylic bone cements (ALABC) spacers are routinely used in the treatment of prosthetic joint infections. The objectives of our study were to evaluate different ALABC for elution kinetics, thermal stability, and mechanical properties. A 10 or 20% mixture (w/w) beads of medium viscosity bone cement (DePuy, Inc) and vancomycin (VAN), gentamycin (GM), daptomycin (DAP), moxifloxacin (MOX), rifampicin (RIF), cefotaxime (CTX), cefepime (FEP), amoxicillin clavulanate (AmC), ampicillin (AMP), meropenem (MER), and ertapenem (ERT) were formed and placed into wells filled with phosphate-buffered saline. Antibiotic concentrations were determined using high-performance liquid chromatography. Antimicrobial activity was tested against Micrococcus luteus ATCC 9341 or Escherichia coli ATCC 25922. AmC, AMP, and FEP concentration rapidly decreased after day 2, being almost undetectable at day 4. Sustained and high elution rates were observed with VAN, GM, MOX, and RIF for the 30-day duration of the experiment. DAP, MER, ERT, and CTX elution rates constantly decreased from day 4. All antibiotics tested retained antimicrobial activity proving thermal stability. Mechanical properties of ALABC were maintained except when RIF was used. PMID:24231380

  2. Elution kinetics, antimicrobial activity, and mechanical properties of 11 different antibiotic loaded acrylic bone cement.

    PubMed

    Gálvez-López, Ruben; Peña-Monje, Alejandro; Antelo-Lorenzo, Ramón; Guardia-Olmedo, Juan; Moliz, Juan; Hernández-Quero, José; Parra-Ruiz, Jorge

    2014-01-01

    Antibiotic-loaded acrylic bone cements (ALABC) spacers are routinely used in the treatment of prosthetic joint infections. The objectives of our study were to evaluate different ALABC for elution kinetics, thermal stability, and mechanical properties. A 10 or 20% mixture (w/w) beads of medium viscosity bone cement (DePuy, Inc) and vancomycin (VAN), gentamycin (GM), daptomycin (DAP), moxifloxacin (MOX), rifampicin (RIF), cefotaxime (CTX), cefepime (FEP), amoxicillin clavulanate (AmC), ampicillin (AMP), meropenem (MER), and ertapenem (ERT) were formed and placed into wells filled with phosphate-buffered saline. Antibiotic concentrations were determined using high-performance liquid chromatography. Antimicrobial activity was tested against Micrococcus luteus ATCC 9341 or Escherichia coli ATCC 25922. AmC, AMP, and FEP concentration rapidly decreased after day 2, being almost undetectable at day 4. Sustained and high elution rates were observed with VAN, GM, MOX, and RIF for the 30-day duration of the experiment. DAP, MER, ERT, and CTX elution rates constantly decreased from day 4. All antibiotics tested retained antimicrobial activity proving thermal stability. Mechanical properties of ALABC were maintained except when RIF was used.

  3. Blood compatibility assessment of polymers used in drug eluting stent coatings.

    PubMed

    Szott, Luisa Mayorga; Irvin, Colleen A; Trollsas, Mikael; Hossainy, Syed; Ratner, Buddy D

    2016-06-01

    Differences in thrombosis rates have been observed clinically between different drug eluting stents. Such differences have been attributed to numerous factors, including stent design, injury created by the catheter delivery system, coating application technologies, and the degree of thrombogenicity of the polymer. The relative contributions of these factors are generally unknown. This work focuses on understanding the thrombogenicity of the polymer by examining mechanistic interactions with proteins, human platelets, and human monocytes of a number of polymers used in drug eluting stent coatings, in vitro. The importance for blood interactions of adsorbed albumin and the retention of albumin was suggested by the data. Microscopic imaging and immunostaining enhanced the interpretation of results from the lactate dehydrogenase cell counting assay and provided insight into platelet interactions, total quantification, and morphometry. In particular, highly spread platelets may be surface-passivating, possibly inhibiting ongoing thrombotic events. In many of the assays used here, poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) showed a differentiated protein deposition pattern that may contribute to the explanation of the consistently thromboresistant blood-materials interaction for fluororpolymers cited in literature. These results are supportive of one of several possible factors contributing to the good thromboresistant clinical safety performance of PVDF-HFP coated drug eluting stents. PMID:27083991

  4. Intravascular ultrasound characterization of the "black hole" phenomenon after drug-eluting stent implantation.

    PubMed

    Costa, Marco A; Sabate, Manel; Angiolillo, Dominick J; Jimenez-Quevedo, Pilar; Teirstein, Paul; Carter, Andrew; Leon, Martin B; Moses, Jeffrey; Zenni, Martin; Yakubov, Steven; Guzman, Luis A; Gilmore, Paul; Macaya, Carlos; Bass, Theodore A

    2006-01-15

    An intraluminal echolucent tissue, dubbed "black hole," has been identified by intravascular ultrasonography after intracoronary brachytherapy. This study reports the characteristics and incidence of the black hole in patients treated with drug-eluting stent implantation using a sirolimus-eluting stent (SES). We included intravascular ultrasound data from the Compassionate Use of Sirolimus-Eluting Stent (SECURE, n = 61 lesions) registry, a study involving patients in whom previous brachytherapy had failed, and the DIABETES trial (n = 165 lesions), a multicenter, randomized study comparing SES versus bare metal stents in diabetic patients. Intravascular ultrasound follow-up was scheduled at 8 months (SECURE trial, post-brachytherapy population) and 9 months (DIABETES trial). In the SECURE population, a black hole was observed in 10 patients (19.6%). Seven black hole segments had significant intimal hyperplasia (> 10%). A black hole accounted for 27% of total intraluminal tissue. In the DIABETES trial, 2 patients (2.5%) in the SES group and none in the bare metal stent group showed echolucent intimal hyperplasia. In conclusion, a black hole occurred frequently after implantation of a SES in patients in whom intracoronary brachytherapy had previously failed. Black holes were also identified in a nonirradiated population, although the incidence was lower than in the post-brachytherapy patients. Bare metal stents were not associated with this phenomenon.

  5. Retention prediction and separation optimization under multilinear gradient elution in liquid chromatography with Microsoft Excel macros.

    PubMed

    Fasoula, S; Zisi, Ch; Gika, H; Pappa-Louisi, A; Nikitas, P

    2015-05-22

    A package of Excel VBA macros have been developed for modeling multilinear gradient retention data obtained in single or double gradient elution mode by changing organic modifier(s) content and/or eluent pH. For this purpose, ten chromatographic models were used and four methods were adopted for their application. The methods were based on (a) the analytical expression of the retention time, provided that this expression is available, (b) the retention times estimated using the Nikitas-Pappa approach, (c) the stepwise approximation, and (d) a simple numerical approximation involving the trapezoid rule for integration of the fundamental equation for gradient elution. For all these methods, Excel VBA macros have been written and implemented using two different platforms; the fitting and the optimization platform. The fitting platform calculates not only the adjustable parameters of the chromatographic models, but also the significance of these parameters and furthermore predicts the analyte elution times. The optimization platform determines the gradient conditions that lead to the optimum separation of a mixture of analytes by using the Solver evolutionary mode, provided that proper constraints are set in order to obtain the optimum gradient profile in the minimum gradient time. The performance of the two platforms was tested using experimental and artificial data. It was found that using the proposed spreadsheets, fitting, prediction, and optimization can be performed easily and effectively under all conditions. Overall, the best performance is exhibited by the analytical and Nikitas-Pappa's methods, although the former cannot be used under all circumstances.

  6. Megasonic sonication for cost-effective and automatable elution of Cryptosporidium from filters and membranes.

    PubMed

    Kerrouche, Abdelfateh; Desmulliez, Marc P Y; Bridle, Helen

    2015-11-01

    Sample processing is a highly challenging stage in the monitoring of waterborne pathogens. This step is time-consuming, requires highly trained technicians and often results in low recovery rates of pathogens. In the UK but also in other parts of the world, Cryptosporidium is the only pathogen directly tested for in routine operational monitoring. The traditional sampling process involves the filtration of 1000L of water, semi-automated elution of the filters and membranes with recovery rates of about 30-40% typically. This paper explores the use of megasonic sonication in an attempt to increase recovery rates and reduce both the time required for processing and the number of labour-intensive steps. Results demonstrate that megasonic energy assisted elution is equally effective as the traditional manual process in terms of recovery rates. Major advantages are however offered in terms of reduction of the elution volume enabling the current centrifugation stage to be avoided. This saves time, equipment and staff costs and critically removes the step in the process that would be most challenging to automate, paving the way thereby for highly effective automated solutions to pathogens monitoring. PMID:26363087

  7. Elution of leachable components from composites after LED and halogen light irradiation.

    PubMed

    Yap, Adrian U J; Han, Varian T S; Soh, M S; Siow, K S

    2004-01-01

    This study investigated the influence of curing lights and modes on the elution of leachable components from dental composites. Four LED/halogen curing lights (LED-Elipar Freelight [FL], 3M-ESPE and GC e-light [EL], GC; high intensity halogen-Elipar Trilight [TL], 3M-ESPE; very high intensity halogen-Astralis 10 [AS], Ivoclar Vivadent) were selected for this study. Pulse (EL1), continuous (FL1, EL2, TL1), turbo (EL3, AS) and soft-start (FL2, EL4, TL2) curing modes of the various lights were examined. A conventional continuous cure halogen light (Max [MX], Dentsply-Caulk) was used for comparison. Three composite (Z100, 3M-ESPE) specimens (6.5 mm in diameter and 1-mm thick) were made for each curing light-mode combination. After polymerization, the specimens were stored in air at 37 degrees C for 24 hours and incubated in acetonitrile at 37 degrees C for 24 hours. BisGMA and TEGDMA extracts were isolated by high performance liquid chromatography (HPLC). Data were subjected to analysis using one-way ANOVA/Scheffe's post-hoc test and Independent Samples t-test at significance level 0.05. The total monomer (BisGMA and TEGDMA) eluted ranged from 8.75 to 27.97 ppm for FL1 and AS, respectively. Significantly more unreacted monomers were leached from composites cured with all modes of EL and AS when compared to MX. No significant difference in the total monomer eluted was observed between the two modes of FL/TL and MX Although composites cured with EL2 released significantly less monomer than EL1, 3 and 4, no significant difference in the total monomer eluted was observed between the continuous and soft-start modes of FL and TL. The elution of leachable components from composites appears to be curing light specific rather than light source (LED or halogen) and curing mode specific.

  8. Protein adsorption to poly(ethylenimine)-modified Sepharose FF. IV. Dynamic adsorption and elution behaviors.

    PubMed

    Liu, Na; Yu, Lin-Ling; Sun, Yan

    2014-10-01

    We have previously investigated bovine serum albumin (BSA) uptake to poly(ethylenimine) (PEI)-grafted Sepharose FF. It was found that there was a critical ionic capacity (cIC; 600mmol/L) for BSA, above which the protein adsorption capacity and uptake kinetics increased drastically. In this work, two poly(ethylenimine) (PEI)-grafted resins with IC values of 271mmol/L (FF-PEI-L270) and 683mmol/L (FF-PEI-L680), which were below and above the cIC, respectively, were chosen to investigate the breakthrough and linear gradient elution (LGE) behaviors of BSA. Commercially available anion exchanger, Q Sepharose FF, was used for comparison. The DBC values of FF-PEI-L680 were much higher in the entire residence time range (2-10min) than the other two resins due to its high static adsorption capacity and uptake kinetics. At a residence time of 5.0min, the DBC of FF-PEI-L680 (104mg/mL) was about seven times that of FF-PEI-L270 and three times that of Q Sepharose FF. A rise-fall trend of the DBCs with increasing ionic strength (IS) was found for all the three resins studied, indicating the presence of electrostatic exclusion for protein uptake at low IS. With increasing NaCl concentration from 20 to 200mmol/L, FF-PEI-L680 kept very high DBC values (64-114mg/mL). In addition, FF-PEI-L270 showed more favorable adsorption properties than Q Sepharose FF at 100-300mmol/L NaCl. These results proved that the three-dimensional grafting ion exchange layer on the PEI resins enhanced their tolerance to IS. In the study of LGE, the three resins showed similar elution behaviors and no distinct peak tailings were observed. The salt concentrations at the elution peaks (IR) were in the order of FF-PEI-L680>FF-PEI-L270>Q Sepharose FF, indicating that the elution for the PEI resins needed higher salt concentrations, which was also an appearance of the salt-tolerant feature of the PEI resins. When protein loading amount was increased to the value equivalent to the DBC at 10% breakthrough, the

  9. Protein adsorption to poly(ethylenimine)-modified Sepharose FF. IV. Dynamic adsorption and elution behaviors.

    PubMed

    Liu, Na; Yu, Lin-Ling; Sun, Yan

    2014-10-01

    We have previously investigated bovine serum albumin (BSA) uptake to poly(ethylenimine) (PEI)-grafted Sepharose FF. It was found that there was a critical ionic capacity (cIC; 600mmol/L) for BSA, above which the protein adsorption capacity and uptake kinetics increased drastically. In this work, two poly(ethylenimine) (PEI)-grafted resins with IC values of 271mmol/L (FF-PEI-L270) and 683mmol/L (FF-PEI-L680), which were below and above the cIC, respectively, were chosen to investigate the breakthrough and linear gradient elution (LGE) behaviors of BSA. Commercially available anion exchanger, Q Sepharose FF, was used for comparison. The DBC values of FF-PEI-L680 were much higher in the entire residence time range (2-10min) than the other two resins due to its high static adsorption capacity and uptake kinetics. At a residence time of 5.0min, the DBC of FF-PEI-L680 (104mg/mL) was about seven times that of FF-PEI-L270 and three times that of Q Sepharose FF. A rise-fall trend of the DBCs with increasing ionic strength (IS) was found for all the three resins studied, indicating the presence of electrostatic exclusion for protein uptake at low IS. With increasing NaCl concentration from 20 to 200mmol/L, FF-PEI-L680 kept very high DBC values (64-114mg/mL). In addition, FF-PEI-L270 showed more favorable adsorption properties than Q Sepharose FF at 100-300mmol/L NaCl. These results proved that the three-dimensional grafting ion exchange layer on the PEI resins enhanced their tolerance to IS. In the study of LGE, the three resins showed similar elution behaviors and no distinct peak tailings were observed. The salt concentrations at the elution peaks (IR) were in the order of FF-PEI-L680>FF-PEI-L270>Q Sepharose FF, indicating that the elution for the PEI resins needed higher salt concentrations, which was also an appearance of the salt-tolerant feature of the PEI resins. When protein loading amount was increased to the value equivalent to the DBC at 10% breakthrough, the

  10. Efficacy and Safety of Biodegradable Polymer Biolimus-Eluting Stents versus Durable Polymer Drug-Eluting Stents: A Meta-Analysis

    PubMed Central

    Zhao, Xiliang; Tian, Zhuang; Zhang, Shuyang

    2013-01-01

    Backgrounds Drug-eluting stents (DES) with biodegradable polymers have been developed to address the risk of thrombosis associated with first-generation DES. We aimed to determine the efficacy and safety of biodegradable polymer biolimus-eluting stents (BES) versus durable polymer DES. Methods Systematic database searches of MEDLINE (1950 to June 2013), EMBASE (1966 to June 2013), the Cochrane Central Register of Controlled Trials (Issue 6 of 12, June 2013), and a review of related literature were conducted. All randomized controlled trials comparing biodegradable polymer BES versus durable polymer DES were included. Results Eight randomized controlled trials investigating 11,015 patients undergoing percutaneous coronary interventions were included in the meta-analysis. The risk of major adverse cardiac events did not differ significantly between the patients treated with the biodegradable polymer BES and the durable polymer DES (Relative risk [RR], 0.970; 95% CI, 0.848–1.111; p = 0.662). However, biodegradable polymer BES was associated with reduced risk of very late ST compared with the durable polymer DES, while the risk of early or late ST was similar (RR for early or late ST, 1.167; 95% CI 0.755–1.802; p = 0.487; RR 0.273; 95% CI 0.115–0.652; p = 0.003; p for interaction = 0.003). Conclusions In this meta-analysis of randomized controlled trials, treatments with biodegradable polymer BES did not significantly reduce the risk of major adverse cardiac events, but demonstrated a significantly lower risk of very late ST when compared to durable polymer DES. This conclusion requires confirmation by further studies with long-term follow-up. PROSPERO register number http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004364#.UnM2lfmsj6J PMID:24244335

  11. Network meta-analysis of balloon angioplasty, nondrug metal stent, drug-eluting balloon, and drug-eluting stent for treatment of infrapopliteal artery occlusive disease

    PubMed Central

    Xiao, Yaowen; Chen, Zhong; Yang, Yaoguo; Kou, Lei

    2016-01-01

    PURPOSE We aimed to conduct a network meta-analysis of mixed treatments for the infrapopliteal artery occlusive disease. METHODS We searched randomized controlled trials (RCTs) regarding balloon angioplasty (BA), nondrug metal stent (NDMS), drug-eluting balloon (DEB), or drug-eluting stent (DES) in PubMed, Embase, CENTRAL, Ovid, Sinomed, and other relevant websites. We selected and assessed the trials that met the inclusion criteria and conducted a network meta-analysis using the ADDIS software. RESULTS We included 11 relevant trials. We analyzed data of 1322 patients with infrapopliteal artery occlusive disease, of which 351 were in the NDMS vs. DES trials, 231 in the NDMS vs. BA trials, 490 in the BA vs. DEB trials, 50 in the DEB vs. DES trials, and 200 in the BA vs. DES trials. The network meta-analysis indicated that with NDMS as the reference, DES had a better result with respect to restenosis (odds ratio [OR], 5.16; 95% credible interval [CI], 1.58–18.41; probability of the best treatment, 84%) and amputation (OR, 2.50; 95% CI, 0.81–7.11; probability of the best treatment, 61%) and DEB had a better result with respect to target lesion revascularization (TLR; OR, 3.74; 95% CI, 0.78–17.05; probability of the best treatment, 57%). Moreover, with BA as the reference, NDMS had a better result with respect to technical success (OR, 0.10; 95% CI, 0.00–1.15; probability of the best treatment, 86%). CONCLUSION Our meta-analysis revealed that DES is a better treatment with respect to short-term patency and limb salvage rate, NMDS may provide a better technical success, and DEB and DES are good choices for reducing revascularization. PMID:27559766

  12. Filter elution assyas for DNA damage : practical and mechanistic significance of the DNA on the filter support.

    SciTech Connect

    Blazek, E. R.; Peak, J. G.; Biological and Medical Research; Rush Presbyterian St. Luke's Medical Center

    1992-01-01

    The alkaline and neutral (or nondenaturing) filter elution assays are popular methods for the measurement of DNA strand breakage and its repair in eukaryotic cells. In both alkaline and neutral elution, it is recommended practice to wash the filter support after removal of the filter and to analyze the DNA recovered by this procedure together with that remaining on the filter as uneluted DNA, although it is not obvious why the DNA in the filter support wash should be so interpreted. We have observed that the sum of the DNA on the filter and that recovered in the filter support wash is approximately constant when the pH of the alkaline filter elution assay for total strand breaks is increased from 12.1 to 12.6, whereas the fraction on the filter itself is markedly smaller at the higher pH. This behavior characterized DNA elution from undamaged cells, as well as from cells treated with various DNA-damaging agents. These findings are consistent with the 'tug-of-war' mechanism that has been proposed for alkaline elution, but are inconsistent with the simplest mechanism of the 'sieve' class. In the neutral filter elution assay for double-strand breaks, by contrast, the distribution of DNA between the filter and the filter support wash is pH-independent. This suggests that single- and double-stranded DNA segments traverse a filter by different physical mechanisms. Our observations underscore the importance of carrying out the filter support wash and the analysis of the DNA it contains as uneluted DNA in alkaline elution, while indicating that a different analysis of this DNA might be appropriate for neutral elution.

  13. Comparison of zonal elution and nonlinear chromatography in determination of the interaction between seven drugs and immobilised β(2)-adrenoceptor.

    PubMed

    Li, Qian; Wang, Jing; Zheng, Yuqing Yuan; Yang, Lingjian; Zhang, Yajun; Bian, Liujiao; Zheng, Jianbin; Li, Zijian; Zhao, Xinfeng; Zhang, Youyi

    2015-07-01

    Zonal elution and nonlinear chromatography are two mainstream models for the determination of drug-protein interaction in affinity chromatography. This work intended to compare the results by zonal elution with that by nonlinear chromatography when it comes to the analysis of the interaction between seven drugs and immobilised β2-adrenoceptor (β2-AR). The results of the zonal elution showed that clorprenaline, clenbuterol, methoxyphenamine, salbutamol, terbutaline, tulobuterol and bambuterol have only one type of binding site on immobilised β2-AR, while nonlinear chromatography confirmed the existence of at least two types of binding sites between β2-AR and clorprenaline, clenbuterol and bambuterol. On these sites, both zonal elution and nonlinear chromatography presented the same rank order for the association constants of the seven drugs. Compared with the data from zonal elution, the association constants calculated using nonlinear chromatography gave a good linear response to the corresponding values by radio-ligand binding assay. The sampling efficiencies of nonlinear chromatography were clearly higher than zonal elution. Nonlinear chromatography will probably become a powerful alternative for the high throughput determination of drug-protein interaction.

  14. Influence of amount of oxidizing slag discharged from stainless steelmaking process of electric arc furnace on elution behavior into fresh water

    NASA Astrophysics Data System (ADS)

    Yokoyama, S.; Shimomura, T.; Hisyamudin, M. N. N.; Takahashi, T.; Izaki, M.

    2012-03-01

    Fundamental study was carried out for provision for acidification of soil due to acid rain. The influence of weight of the additive slag on elution behavior of the slag into water was studied in this study. Elution experiment was carried out on a basis of JIS K 0058-1. Generally, the pH in the aqueous solution increased with an increase in weight of the additive slag. The pH converged to approximately eight. Calcium, magnesium and manganese, which were essential elements for plants, were eluted from the slag irrespective to elution condition. The eluted concentrations of Ca and Mg increased with an increase in weight of the additive slag. Silicon and zinc were also eluted depending on the conditions. Aluminum that was harmful for plants was not eluted from the used slag.

  15. Quantitative and isomeric determination of amphetamine and methamphetamine from urine using a nonprotic elution solvent and R(-)-alpha-methoxy-alpha-trifluoromethylphenylacetic acid chloride derivatization.

    PubMed

    Holler, Justin M; Vorce, Shawn P; Bosy, Thomas Z; Jacobs, Aaron

    2005-10-01

    Forensic Urine Drug Testing Laboratories often requires two confirmatory methods for a methamphetamine positive screen. First, methamphetamine is identified and quantitated using gas chromatography-mass spectrometry. If the total methamphetamine concentration is above the administrative cutoff level, the isomeric composition must be determined. This eliminates a possible contribution by over-the-counter cold medications that contain l-methamphetamine (Vick's inhalers). Products that contain only the l-isomer of methamphetamine must be distinguishable from prescription or illicitly manufactured methamphetamine, which consists mainly of the d-isomer. Optically impure derivatizing reagents will produce an impure mixture from a pure isomeric compound. Therefore, methods utilizing impure reagents can prove problematic when interpreting results. Use of an optically pure chiral derivatizing reagent, such as R(-)-alpha-methoxy-alpha-trifluoromethylphenylacetic acid chloride, allows for the creation and measurement of chromatographically separable isomeric compounds. The novel method described here utilizes a polymer-based solid-phase column adapted to a positive pressure manifold extraction system and a one-step derivatization process that occurs directly in the elution solvent. This methodology eliminates an elution solvent dry-down step that may adversely affect recovery of volatile amphetamine compounds. Although the method was designed for the quantitative analysis of the isomers of amphetamine and methamphetamine, it can be adapted for use with a wide range of phenethylamines including methylenedioxyamphetamine, N-methylenedioxymethamphetamine, and possibly N-methylenedioxyethylamphetamine. The linear range for quantitation was 25-10,000 ng/mL for d,l-methamphetamine and d,l-amphetamine, and correlation coefficients were 0.997 or better. The coefficient of variation for all four analytes did not exceed 2.8%. Concentrations analyzed ranged from 500 to 4000 ng/mL (n=40

  16. Sustained Antibiotic-Eluting Intra-Ocular Lenses: A New Approach

    PubMed Central

    Tan, Dulcia W. N.; Lim, Soo Ghim; Wong, Tina T.; Venkatraman, Subbu S.

    2016-01-01

    Currently, infections following cataract surgery are not as effectively managed with antibiotic eye drops, which suffer from poor bioavailability of drug and low patient compliance. The ideal solution, which can help to overcome the issue of drug wastage and poor bioavailabilty, as well as the need for frequent applications (patient inconvenience), is a drug-eluting intraocular lens (IOL). We describe a novel approach to such a drug-eluting lens by using a peripheral IOL attachment as a drug depot to deliver antibiotics, Levofloxacin (LFX) or Moxifloxacin (MFX). In this work, drug was entrapped within a fully-degradable polymer, poly(L-lactide-co-ɛ-caprolactone) (PLC). The effects of drug loading and solvent type on drug release and film morphology were investigated using cast films. The study clearly demonstrated that a slower-evaporating solvent tetrahydrofuran (THF) resulted in a better surface morphology, as well as lower initial burst compared to dichloromethane (DCM), and hence, was better suited to developing a drug-eluting attachment with sustained release of drug. When attachments were fabricated with drugs at high loading percentages (20% and 25% in polymer), significant burst was observed compared to films: this is attributed to the higher surface-to-volume ratio of the attachments. When the levofloxacin (LFX) loading percentage was decreased to 3% and 5%, the attachments presented lower burst and sustained release with therapeutic efficacy. This work has demonstrated the potential of using an IOL attachment as a more efficacious anti-infective option compared to daily eye drops. PMID:27741256

  17. A theoretical plate model accounting for slow kinetics in chromatographic elution.

    PubMed

    Baeza-Baeza, J J; García-Álvarez-Coque, M C

    2011-08-01

    The chromatographic elution has been studied from different perspectives. However, in spite of the simplicity and evident deficiencies of the plate model proposed by Martin and Synge, it has served as a basis for the characterization of columns up-to-date. This approach envisions the chromatographic column as an arbitrary number of theoretical plates, each of them consisting of identical repeating portions of mobile phase and stationary phase. Solutes partition between both phases, reaching the equilibrium. Mobile phase transference between the theoretical plates is assumed to be infinitesimally stepwise (or continuous), giving rise to the mixing of the solutions in adjacent plates. This yields an additional peak broadening, which is added to the dispersion associated to the equilibrium conditions. It is commonly assumed that when the solute concentration is sufficiently small, chromatographic elution is carried out under linear conditions, which is the case in almost all analytical applications. When the solute concentration increases above a value where the stationary phase approximates saturation (i.e. becomes overloaded), non-linear elution is obtained. In addition to overloading, another source of non-linearity can be a slow mass transfer. An extended Martin and Synge model is here proposed to include slow mass-transfer kinetics (with respect to flow rate) between the mobile phase and stationary phase. We show that there is a linear relationship between the variance and the ratio of the kinetic constants for the mass transfer in the flow direction (τ) and the mass transfer between the mobile phase and stationary phase (ν), which has been called the kinetic ratio (κ=τ/ν). The proposed model was validated with data obtained according to an approach that simulates the solute migration through the theoretical plates. An experimental approach to measure the deviation from the equilibrium conditions using the experimental peak variances and retention times at

  18. Antibiotic eluting clay mineral (Laponite®) for wound healing application: an in vitro study.

    PubMed

    Ghadiri, M; Chrzanowski, W; Rohanizadeh, R

    2014-11-01

    Different materials in form of sponge, hydrogel and film have been developed and formulated for treating and dressing burn wounds. In this study, the potential of Laponite, a gel forming clay, in combination with an antimicrobial agent (mafenide), as a wound dressing material was tested in vitro. Laponite/mafenide (Lap/Maf) hydrogel was formulated in three different ratios of Lap/Maf 1:1, 1:2, 1:3. Laponite/mafenide/alginate (Lap/Maf/Alg) film was also formulated by combining Lap/Maf gel (1:1) with alginate. Intercalation rate of mafenide into the layers of Laponite nanoparticles and physico-chemical properties, including wound dressing characteristics of materials were studied using various analytical methods. Furthermore, the degradation of materials and the release profile of mafenide were investigated in simulated wound exudates fluid and antibacterial effectiveness of the eluted mafenide was tested on a range of bacterial species. The cytotoxicity of materials was also evaluated in skin fibroblast culture. The results showed that mafenide molecules were intercalated between the nano-sized layers of Laponite. The eluted mafenide showed active antibacterial effects against all three tested bacteria. All intercalated mafenide released from Lap/Maf 1:1 and 1:2 gel formulations and nearly 80% release from 1:3 formulation during test period. No significant difference was observed in release profile of mafenide between Lap/Maf/Alg film and Lap/Maf formulations. Wound dressing tests on Lap/Maf/Alg film showed it is a breathable dressing and has capacity to absorb wound exudates. The study showed that prepared Lap/Maf composite has the potential to be used as an antibiotic eluting gel or film for wound healing application. Additionally, Laponite has shown benefits in wound healing processes by releasing Mg(2+) ions and thereby reducing the cytotoxic effect of mafenide on fibroblast cells.

  19. Elution power of a solvent as a criterion of relative lipid polarity

    NASA Astrophysics Data System (ADS)

    Pchelkin, V. P.

    2016-09-01

    New parameters are proposed that allow reliable calculation of fixed hydrophilicity values for different classes of lipids over the widest possible range, based on the elution power of solvents and using two compounds at the boundaries of the range as standards. The values of relative hydrophilicity are calculated from the values of relative chromatographic mobility of these types of compounds. It is established that the levels of hydrophilicity of different classes of lipids relative to the selected hexadecane-glycerol pair do not depend on the composition of the different mobile phases used in either planar or column types of liquid chromatography for the separation of complex lipid mixtures.

  20. Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

    SciTech Connect

    Poggi, Guido; Quaretti, Pietro; Montagna, Benedetta Sottotetti, Federico Tagliaferri, Barbara Pozzi, Emma Amatu, Alessio Pagella, Chiara; Bernardo, Giovanni

    2011-02-15

    Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

  1. Elution characteristics of vancomycin, teicoplanin, gentamicin and clindamycin from calcium sulphate beads.

    PubMed

    Wichelhaus, T A; Dingeldein, E; Rauschmann, M; Kluge, S; Dieterich, R; Schäfer, V; Brade, V

    2001-07-01

    The in vitro release of vancomycin, teicoplanin, gentamicin and clindamycin from biodegradable calcium sulphate (CaSO(4)) carrier beads is described. All antibiotics showed prolonged release from the carrier beads, which was elevated during the first 24 h, with peak levels exceeding 2500 microg/bead. Doubling the antibiotic load of the beads revealed a more prolonged elution and a two-fold increase in antibiotic release. Local carrier-associated antibiotic treatment with CaSO(4) beads may prove to be effective in the management of chronic bone infections.

  2. Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

    SciTech Connect

    Pua, Uei

    2013-06-15

    Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192-198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960-966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.

  3. Determination of cadmium in river water by sequential metal vapor elution analysis.

    PubMed

    Ohta, K; Nakajima, N; Inui, S Y; Winefordner, J D; Mizuno, T

    1992-12-01

    Determination of cadmium in river water by sequential metal vapour elution analysis (column temperature; > 1500 K) with argon and hydrogen carrier gas and with atomic absorption spectrometric detection is described. The column is made of a molybdenum capillary tube (i.d. 1.22 mm) and the temperature is 1760 K. The cadmium vapor was separated from those of calcium, iron and sodium. The calibration graph was linear up to 15 mu/ml. Relative standard deviations of 0.8-4.3% were obtained in the range 1 to 15 mu/ml. Cadmium in spiked samples (river water) was determined. The results were in good agreement with the amount spiked.

  4. Economic analysis of endovascular drug-eluting treatments for femoropopliteal artery disease in the UK

    PubMed Central

    Katsanos, Konstantinos; Garner, Abigail M; Zayed, Hany; Cleveland, Trevor; Pietzsch, Jan B

    2016-01-01

    Objectives To estimate the clinical and economic impact of drug-eluting endovascular treatment strategies for femoropopliteal artery disease compared with current standard of care. Design Systematic literature search to pool target lesion revascularisations (TLR). Model-based per-patient cost impact and quasi-cost-effectiveness projection over 24 months based on pooled TLRs and current reimbursement. Setting The UK's National Health Service (NHS). Participants Patients presenting with symptomatic femoropopliteal disease eligible for endovascular treatment. Interventions Current National Institute for Health and Care Excellence (NICE) guideline-recommended treatment with percutaneous transluminal balloon angioplasty (PTA) and bailout bare metal stenting (BMS) versus primary BMS placement, or drug-coated balloon (DCB), or drug-eluting stent (DES) treatment. Primary and secondary outcome measures 24-month per-patient cost impact to NHS (primary outcome). Secondary outcomes: pooled 24-month TLR rates; numbers needed to treat (NNTs); cost per TLR avoided and estimated incremental cost-effectiveness ratio (ICER) in £ per quality-adjusted life year (QALY). Results N=28 studies were identified, reporting on 5167 femoropopliteal lesions. Over 24 months, DCB, DES and BMS reduced TLRs of de novo lesions from 36.2% to 17.6%, 19.4% and 26.9%, respectively, at an increased cost of £43, £44 and £112. NNTs to avoid 1 TLR in 24 months were 5.4, 6.0 and 10.8, resulting in cost per TLR avoided of £231, £264 and £1204. DCB was estimated to add 0.011 QALYs, DES 0.010 QALYs and BMS 0.005 QALYs, resulting in estimated ICERs of £3983, £4534 and £20 719 per QALY gained. A subset analysis revealed more favourable clinical and economic outcomes for a 3.5 µg/mm2 DCB with urea excipient, compared with the rest of DCBs. A modest reduction of 10% in DCB and DES prices made drug-eluting treatments dominant. Conclusions Widespread adoption of drug-eluting endovascular

  5. Are Everolimus-Eluting Stents Associated With Better Clinical Outcomes Compared to Other Drug-Eluting Stents in Patients With Type 2 Diabetes Mellitus?

    PubMed Central

    Bundhun, Pravesh Kumar; Pursun, Manish; Teeluck, Abhishek Rishikesh; Long, Man-Yun

    2016-01-01

    Abstract Controversies still exist with the use of Everolimus-Eluting Stents (EES) compared to other Drug-Eluting Stents (DES) in patients with Type 2 Diabetes Mellitus (T2DM). Therefore, in order to solve this issue, we aim to compare the 1-year adverse clinical outcomes between EES and non-EE DES with a larger number of patients with T2DM. Medline, EMBASE, PubMed databases, as well as the Cochrane library were searched for randomized controlled trials (RCTs) and observational studies (OS) comparing EES and non-EE DES in patients with T2DM. One-year adverse outcomes were considered as the clinical endpoints in this study. Odd ratios (OR) with 95% confidence interval (CI) were used to express the pooled effect on discontinuous variables and the pooled analyses were performed with RevMan 5.3. Ten studies consisting of a total of 11,981 patients with T2DM (6800 patients in the EES group and 5181 in the non-EE DES group) were included in this meta-analysis. EES were associated with a significantly lower major adverse cardiac events (MACEs) with OR: 0.83, 95% CI: 0.70–0.98, P = 0.03. Revascularization including target vessel revascularization (TVR) and target lesion revascularization (TLR) were also significantly lower in the EES group with OR: 0.62, 95% CI: 0.40–0.94, P = 0.03 and OR: 0.74, 95% CI: 0.57–0.95, P = 0.02, respectively. Also, a significantly lower rate of stent thrombosis with OR: 0.63, 95% CI: 0.46–0.86, P = 0.003 was observed in the EES group. However, a similar mortality rate was reported between the EES and non-EE DES groups. During this 1-year follow-up period, EES were associated with significantly better clinical outcomes compared to non-EE DES in patients suffering from T2DM. However, further research comparing EES with non-EE DES in insulin-treated and noninsulin-treated patients with T2DM are recommended. PMID:27057888

  6. Numerical modeling of the elution peak profiles of retained solutes in supercritical fluid chromatography

    SciTech Connect

    Kaczmarski, Krzysztof; Guiochon, Georges A

    2011-01-01

    In supercritical fluid chromatography (SFC), the significant expansion of the mobile phase along the column causes the formation of axial and radial gradients of temperature. Due to these gradients, the mobile phase density, its viscosity, its velocity, its diffusion coefficients, etc. are not constant throughout the column. This results in a nonuniform flow velocity distribution, itself causing a loss of column efficiency in certain cases, even at low flow rates, as they do in HPLC. At high flow rates, an important deformation of the elution profiles of the sample components may occur. The model previously used to account satisfactorily for the retention of an unsorbed solute in SFC is applied to the modeling of the elution peak profiles of retained compounds. The numerical solution of the combined heat and mass balance equations provides the temperature and the pressure profiles inside the column and values of the retention time and the band profiles of retained compounds that are in excellent agreement with independent experimental data for large value of mobile phase reduced density. At low reduced densities, the band profiles can strongly depend on the column axial distribution of porosity.

  7. Role of adjunct pharmacologic therapy in the era of drug-eluting stents.

    PubMed

    Douglas, John S

    2005-12-15

    The success of percutaneous coronary intervention (PCI) has historically been limited by a relatively high rate of restenosis, a response of the coronary artery to trauma induced during PCI. Bare-metal stents, by providing a supportive intravascular scaffolding, have significantly reduced the incidence of restenosis compared with traditional balloon PCI. However, significant loss of lumen within the bare-metal device (in-stent restenosis) occurs in 10-30% of patients within 6 months of the procedure. The recent introduction of drug-eluting stents, permitting local delivery of high concentrations of immunosuppressive or anti-proliferative agents, promises to prevent the processes underlying restenosis. Although these devices have been successful in providing an incremental reduction in rates of restenosis, they are expensive. To date, clinical trials of pharmacologic treatment have failed to demonstrate a clinically significant impact on restenosis. Recently, results of the Cilostazol for Restenosis (CREST) trial, a randomized, double-blind study, show that cilostazol reduces the risk of restenosis in patients who receive bare-metal stents, including high-risk patients. Effective adjunct pharmacologic therapy to prevent in-stent restenosis, therefore, remains desirable, particularly in patients receiving bare-metal stents, and potentially in patients receiving drug-eluting stents who are at high risk for restenosis (i.e., those with diabetes, long lesions, and small vessels).

  8. Strontium eluting graphene hybrid nanoparticles augment osteogenesis in a 3D tissue scaffold.

    PubMed

    Kumar, Sachin; Chatterjee, Kaushik

    2015-02-01

    The objective of this work was to prepare hybrid nanoparticles of graphene sheets decorated with strontium metallic nanoparticles and demonstrate their advantages in bone tissue engineering. Strontium-decorated reduced graphene oxide (RGO_Sr) hybrid nanoparticles were synthesized by the facile reduction of graphene oxide and strontium nitrate. X-ray diffraction, transmission electron microscopy, and atomic force microscopy revealed that the hybrid particles were composed of RGO sheets decorated with 200-300 nm metallic strontium particles. Thermal gravimetric analysis further confirmed the composition of the hybrid particles as 22 wt% of strontium. Macroporous tissue scaffolds were prepared by incorporating RGO_Sr particles in poly(ε-caprolactone) (PCL). The PCL/RGO_Sr scaffolds were found to elute strontium ions in aqueous medium. Osteoblast proliferation and differentiation was significantly higher in the PCL scaffolds containing the RGO_Sr particles in contrast to neat PCL and PCL/RGO scaffolds. The increased biological activity can be attributed to the release of strontium ions from the hybrid nanoparticles. This study demonstrates that composites prepared using hybrid nanoparticles that elute strontium ions can be used to prepare multifunctional scaffolds with good mechanical and osteoinductive properties. These findings have important implications for designing the next generation of biomaterials for use in tissue regeneration. PMID:25553731

  9. Drug-eluting Ti wires with titania nanotube arrays for bone fixation and reduced bone infection

    NASA Astrophysics Data System (ADS)

    Gulati, Karan; Aw, Moom Sinn; Losic, Dusan

    2011-10-01

    Current bone fixation technology which uses stainless steel wires known as Kirschner wires for fracture fixing often causes infection and reduced skeletal load resulting in implant failure. Creating new wires with drug-eluting properties to locally deliver drugs is an appealing approach to address some of these problems. This study presents the use of titanium [Ti] wires with titania nanotube [TNT] arrays formed with a drug delivery capability to design alternative bone fixation tools for orthopaedic applications. A titania layer with an array of nanotube structures was synthesised on the surface of a Ti wire by electrochemical anodisation and loaded with antibiotic (gentamicin) used as a model of bone anti-bacterial drug. Successful fabrication of TNT structures with pore diameters of approximately 170 nm and length of 70 μm is demonstrated for the first time in the form of wires. The drug release characteristics of TNT-Ti wires were evaluated, showing a two-phase release, with a burst release (37%) and a slow release with zero-order kinetics over 11 days. These results confirmed our system's ability to be applied as a drug-eluting tool for orthopaedic applications. The established biocompatibility of TNT structures, closer modulus of elasticity to natural bones and possible inclusion of desired drugs, proteins or growth factors make this system a promising alternative to replace conventional bone implants to prevent bone infection and to be used for targeted treatment of bone cancer, osteomyelitis and other orthopaedic diseases.

  10. Strontium eluting graphene hybrid nanoparticles augment osteogenesis in a 3D tissue scaffold.

    PubMed

    Kumar, Sachin; Chatterjee, Kaushik

    2015-02-01

    The objective of this work was to prepare hybrid nanoparticles of graphene sheets decorated with strontium metallic nanoparticles and demonstrate their advantages in bone tissue engineering. Strontium-decorated reduced graphene oxide (RGO_Sr) hybrid nanoparticles were synthesized by the facile reduction of graphene oxide and strontium nitrate. X-ray diffraction, transmission electron microscopy, and atomic force microscopy revealed that the hybrid particles were composed of RGO sheets decorated with 200-300 nm metallic strontium particles. Thermal gravimetric analysis further confirmed the composition of the hybrid particles as 22 wt% of strontium. Macroporous tissue scaffolds were prepared by incorporating RGO_Sr particles in poly(ε-caprolactone) (PCL). The PCL/RGO_Sr scaffolds were found to elute strontium ions in aqueous medium. Osteoblast proliferation and differentiation was significantly higher in the PCL scaffolds containing the RGO_Sr particles in contrast to neat PCL and PCL/RGO scaffolds. The increased biological activity can be attributed to the release of strontium ions from the hybrid nanoparticles. This study demonstrates that composites prepared using hybrid nanoparticles that elute strontium ions can be used to prepare multifunctional scaffolds with good mechanical and osteoinductive properties. These findings have important implications for designing the next generation of biomaterials for use in tissue regeneration.

  11. Usefulness of Everolimus-Eluting Coronary Stent Implantation in Patients on Maintenance Hemodialysis.

    PubMed

    Ikari, Yuji; Kyono, Hiroyuki; Isshiki, Takaaki; Ishizuka, Shuichi; Nasu, Kenya; Sano, Koichi; Okada, Hisayuki; Sugano, Teruyasu; Uehara, Yoshiki

    2015-09-15

    The outcomes of second-generation drug-eluting stent (DES) are unknown in patients on maintenance hemodialysis (HD) although HD has been reported as a strong predictor of adverse outcome after the first-generation DES implantation. The OUCH-PRO Study is a prospective multicenter single-arm registry design to study clinical and angiographic outcomes after everolimus-eluting stent (EES). Patients who underwent maintenance HD were prospectively enrolled at the time of elective coronary intervention using EES. Quantitative coronary angiography was performed in an independent core laboratory. The primary end point was the occurrence of target vessel failure (TVF) defined as cardiac death, myocardial infarction (MI), and target vessel revascularization at 1 year. A total of 123 patients were enrolled and 161 EES were implanted. The TVF rate at 1 year was 18% (4% cardiac death, 0% MI, 17% target vessel revascularization). No stent thrombosis was documented. Other clinical events at 1 year were 3% noncardiac death, 3% stroke, and 9% non-target-vessel revascularization. Late lumen loss in stent was 0.37 ± 0.63 mm at 8 months. In conclusion, EES had a high TVF rate and great late lumen loss in patients on HD compared with previous huge EES data in non-HD patients. PMID:26219496

  12. New drug-eluting lenses to be applied as bandages after keratoprosthesis implantation.

    PubMed

    Carreira, A S; Ferreira, P; Ribeiro, M P; Correia, T R; Coutinho, P; Correia, I J; Gil, M H

    2014-12-30

    Corneal tissue is the most commonly transplanted tissue worldwide. This work aimed to develop a new drug-eluting contact lens that may be used as a bandage after keratoprosthesis. During this work, films were produced using poly(vinyl alcohol) (PVA) and chitosan (CS) crosslinked with glyoxal (GL). Vancomycin chlorhydrate (VA) was impregnated in these systems by soaking. Attenuated total reflectance - Fourier transform infrared spectroscopy was used to confirm crosslinking. The cytotoxic and drug release profile, hydrophilicity, thermal and biodegradation as well as swelling capacity of the samples were assessed through in vitro studies. PVA and PVA/CS films were obtained by crosslinking with GL. The films were transparent, flexible with smooth surfaces, hydrophilic and able to load and release vancomycin for more than 8h. Biodegradation in artificial lachrymal fluid (ALF) with lysozyme at 37°C showed that mass loss was higher for the samples containing CS. Also, the samples prepared with CS showed the formation of pores which were visualized by SEM. All samples revealed a biocompatible character after 24h in contact with cornea endothelial cells. As a general conclusion it was possible to determine that the 70PVA/30CS film showed to combine the necessary features to prepare vancomycin-eluting contact lenses to prevent inflammation after corneal substitution.

  13. Cost analysis of sirolimus-eluting stents in the Japanese health insurance system.

    PubMed

    Sugimoto, Kazumasa; Kobayashi, Yoshio; Kuroda, Nakabumi; Komuro, Issei

    2009-11-01

    The cost-effectiveness of drug-eluting stents (DES) has been evaluated in the United States and Europe, however, there is little information from Japan. The present study evaluated the cost-effectiveness of sirolimus-eluting stents (SES) in Japan. In-hospital and follow-up costs of 25 consecutive patients undergoing SES implantation in a de novo lesion were evaluated. A control group for comparison was composed of 25 consecutive patients undergoing bare metal stent (BMS) implantation in a de novo lesion before the introduction of SES. There was no significant difference in resource use between the SES and BMS groups. Procedural cost (yen1,049,200 +/- 208,793 versus yen896,590 +/- 117,984, P = 0.01) was higher in the SES group than in the BMS group because of the higher reimbursement price of SES (yen378,000 versus yen258,000). In-hospital cost (yen1,202,891 +/- 208,793 versus yen1,050,280 +/- 177,984, P < 0.01) was higher in patients treated with SES. Less target lesion revascularization (4% versus 20%, P = 0.2) in patients with SES reduced the difference; aggregate 1-year cost was not significantly different (yen1,479,481 +/- 284,343 versus yen1,463,640 +/- 495,803, P = 0.9). It is concluded that SES may be cost-effective even in Japan.

  14. Characterizing and modeling of extensive atrazine elution tailing for stable manure-amended agricultural soil.

    PubMed

    Akyol, Nihat Hakan

    2015-01-01

    Non-ideal sorption and extensive elution tailing behavior of atrazine was evaluated for an agricultural soil with and without stable manure amendment (10% by weight). A series of laboratory experiments showed that the sorption of atrazine was described by rate-limited, nonlinear reversible processes (Freundlich isotherm) for both non-amended and amended soil. Non-ideal transport of atrazine exhibited extensive low concentration elution tailing due to the most likely organic carbon fraction in the soil. This tailing behavior was more pronounced and extensive for soil with 10% stable-manure amendment. Two-site transport modeling analyses including non-linear sorption and rate-limited sorption-desorption provided a reasonably good match to the atrazine breakthrough curves but were unable to match the long-term concentration tailing, even for non-amended soil. A mathematical model incorporating nonlinear, rate-limited sorption/desorption described by a continuous-distribution function was used to successfully simulate atrazine transport early-time breakthrough and long-term concentration tailing for both non-amended and amended soil conditions. PMID:25303664

  15. Influence of Multiple Bacterial Populations on Phenanthrene Degradation, Bacterial Cell Elution, and Species Distribution

    NASA Astrophysics Data System (ADS)

    Patterson, B. M.; Brusseau, M. L.; Maier, R. M.; Frye, R.

    2001-05-01

    A single set of degradation coefficients is typically used when representing biodegradation in contaminant transport models. Implicit to this approach is the assumption that only a single degrading isolate exists, or that the entire community of degraders more typically present in natural systems has a uniform, constant growth rate and affinity for the contaminant. This assumption was evaluated through a miscible displacement experiment conducted using a column packed with a soil containing an indigenous microbial community comprised of 24 identified phenanthrene-degrading isolates. Results produced oscillating phenanthrene concentrations in the column effluent, indicating potential competitive interactions among the isolates. A second series of experiments, conducted in a simplified system comprised of sand and 1,2, or 3 indigenous isolates, examined the effects of species interactions on phenanthrene degradation and bacterial cell elution. Bacterial growth rates, density of cells within the column, and bacterial distribution were also evaluated. Results show single bacterial species produced relatively stable cell elution and phenanthrene concentrations in the effluent. Conversely, the behavior in the multiple species systems indicated synergistic and antagonistic interactions occurred among the species. These results illustrate that the dynamics of heterogeneous microbial communities should be considered when evaluating contaminant biodegradation and transport in subsurface systems.

  16. Peak capacity optimization of peptide separations in reversed-phase gradient elution chromatography: fixed column format.

    PubMed

    Wang, Xiaoli; Stoll, Dwight R; Schellinger, Adam P; Carr, Peter W

    2006-05-15

    The optimization of peak capacity in gradient elution RPLC is essential for the separation of multicomponent samples such as those encountered in proteomic research. In this work, we study the effect of gradient time (tG), flow rate (F), temperature (T), and final eluent strength (phi(final)) on the peak capacity of separations of peptides that are representative of the range in peptides found in a tryptic digest. We find that there are very strong interactions between the individual variables (e.g., flow rate and gradient time) which make the optimization quite complicated. On a given column, one should first set the gradient time to the longest tolerable and then set the temperature to the highest achievable with the instrument. Next, the flow rate should be optimized using a reasonable but arbitrary value of phi(final). Last, the final eluent strength should be adjusted so that the last solute elutes as close as possible to the gradient time. We also develop an easily implemented, highly efficient, and effective Monte Carlo search strategy to simultaneously optimize all the variables. We find that gradient steepness is an important parameter that influences peak capacity and an optimum range of gradient steepness exists in which the peak capacity is maximized.

  17. Overcoming the high-temperature two-dimensional gas chromatography limits to elute heavy compounds.

    PubMed

    Mahé, Laure; Courtiade, Marion; Dartiguelongue, Cyril; Ponthus, Jérémie; Souchon, Vincent; Thiébaut, Didier

    2012-03-16

    Overcoming high-temperature (HT) two-dimensional gas chromatography (GC × GC) limits is critical for the analysis of heavy hydrocarbons, particularly those contained in heavy petroleum fractions. To reach this goal, HT-GC × GC analysis was adapted from HT-GC Simulated Distillation (HT-GC SimDist) operating conditions as this analysis embraces compounds whose boiling point ranges from 35 °C to 700 °C and from a previous study that enabled the elution of linear alkane nC(60) and tetraaromatic compounds by HT-GC × GC. This paper shows that HT-GC × GC analysis using CO(2) cryogenic modulator and short wide bore columns with a thin film of stationary phase allows the elution of linear alkanes up to nC(68) (641 °C) as well as of highly aromatic hydrocarbons like coronene. Furthermore, compared to previous studies, an on-column injector was used to reduce discrimination of high boiling point compounds.

  18. Effect of energetic materials wettability on their outdoor effective elution rate.

    PubMed

    Lapointe, Marie-Claude; Martel, Richard; Lange, Sébastien F; Coté, Sébastien

    2016-07-01

    Energetic materials (EM) contained in military ammunitions have been found in the surface soil and water of training areas and may potentially represent a threat to human health and the environment. EM wettability is an essential physical parameter to characterize because it controls EM dissolution rate. This paper was conducted to determine the wettability of conventional and new EM formulations used in military ammunition. Wettability was estimated in the laboratory via contact angle measurements of water droplets on different EM surfaces. Results show that 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitro-1,3,5-triazinane (RDX), Octol and energetic thermoplastic elastomer (ETPE) 1000 are hydrophilic while Composition B, XRT, GIM, CX-85, ETPE 2000, and C4 are hydrophobic whereas HELOVA gun propellant has a mixed wettability oscillating between hydrophilic and hydrophobic. The present study demonstrates that wettability of EM formulation is generally controlled by their matrix constituents. Results indicate that hydrophobic formulations have a much slower outdoor environmental effective elution rate than hydrophilic ones, with the exception of the hydrophobic C4 formulation whose elution rate is extremely high. The addition of hydrophobic components into EM formulations is recommended to diminish the environmental impact on water, as it has already been done with XRT, GIM and CX-85 formulations.

  19. Elution behavior of oligomers on a polyvinyl alcohol gel column with chloroform, methanol, and their mixtures

    SciTech Connect

    Mori, S. )

    1988-01-01

    Elution phenomena of size exclusion chromatography (SEC) plus superimposed adsorption effects for oligostyrenes, epoxy resins, methylated melamine-formaldehyde resin prepolymers, p-cresol-formaldehyde resin prepolymers, and phenol-formaldehyde resin prepolymers were investigated. SEC and superimposed adsorption effects could be elucidated from a concept of solubility parameter. Minimum retention volumes of these obligomers were obtained with the mobile phases of chloroform/methanol, 80/20 or 60/40 (v/v), and separation was expected to be mostly performed by SEC. The solubility parameter of polyvinyl alcohol gels was estimated to be between 21 and 23 from the above results. Elution for normal phase chromatography was in the order of increasing molecular weight and that for reversed-phase chromatography was in the order of decreasing molecular weight. These are reversed phenomena to those for low-molecular weigh compounds. Solubility of sample solutes to mobile phase must be considered. Methanol mobile phase-polyvinyl alcohol gel system might be exception.

  20. Nanoparticle Drug- and Gene-eluting Stents for the Prevention and Treatment of Coronary Restenosis

    PubMed Central

    Yin, Rui-Xing; Yang, De-Zhai; Wu, Jin-Zhen

    2014-01-01

    Percutaneous coronary intervention (PCI) has become the most common revascularization procedure for coronary artery disease. The use of stents has reduced the rate of restenosis by preventing elastic recoil and negative remodeling. However, in-stent restenosis remains one of the major drawbacks of this procedure. Drug-eluting stents (DESs) have proven to be effective in reducing the risk of late restenosis, but the use of currently marketed DESs presents safety concerns, including the non-specificity of therapeutics, incomplete endothelialization leading to late thrombosis, the need for long-term anti-platelet agents, and local hypersensitivity to polymer delivery matrices. In addition, the current DESs lack the capacity for adjustment of the drug dose and release kinetics appropriate to the disease status of the treated vessel. The development of efficacious therapeutic strategies to prevent and inhibit restenosis after PCI is critical for the treatment of coronary artery disease. The administration of drugs using biodegradable polymer nanoparticles as carriers has generated immense interest due to their excellent biocompatibility and ability to facilitate prolonged drug release. Despite the potential benefits of nanoparticles as smart drug delivery and diagnostic systems, much research is still required to evaluate potential toxicity issues related to the chemical properties of nanoparticle materials, as well as to their size and shape. This review describes the molecular mechanism of coronary restenosis, the use of DESs, and progress in nanoparticle drug- or gene-eluting stents for the prevention and treatment of coronary restenosis. PMID:24465275

  1. Effect of Food Stimulated Liquids and Thermocycling on the Monomer Elution from a Nanofilled Composite

    PubMed Central

    Tabatabaei, Masumeh Hasani; Sadrai, Sima; Bassir, Seyed Hossein; Veisy, Nadia; Dehghan, Somaye

    2013-01-01

    The present study was aimed to evaluate the effects of food simulating liquids and thermocycling on the elution of monomers from a nanofilled resin composite in different immersion times. Five Specimen discs were made from a nano-hybrid composite (Supreme 3M) for each group (Total = 180) and immersed in distilled water (control), citric acid, lactic acid, and 75% aqueous ethanol solution. The discs were removed after 24 h, 48 h, 72 h, 1 wk, 4 wk, and 12 wk. Three groups of samples underwent thermocycling for 1000, 2000 and 3000 cycles. The solutes were analyzed with HPLC for detection of eluted monomers. The results showed that the amount of released TEGDMA was significantly higher than that of Bis-GMA; however, there were not any significant differences between the amount of released Bis-GMA and UDMA. Moreover, the highest amount of monomers was released from samples immersed in ethanol solution; samples immersed in citric acid and lactic acid significantly released more monomers than those immersed in distilled water. Furthermore, the immersion time in aqueous ethanol solution had an increasing effect on the release of monomers. In addition, the higher amounts of monomers were release from samples immersed in ethanol and citric acid which underwent a higher number of thermal cycles. In conclusion, food and drink stimulated liquids used in this study increased the amount of some of the monomers released from composite resin. Thermal shocks and storage time are other factors that increased the release of monomers from the composite resin PMID:23986791

  2. Preparation, degradation and in vitro release of ciprofloxacin-eluting ureteral stents for potential antibacterial application.

    PubMed

    Ma, Xiaofei; Xiao, Yan; Xu, Heng; Lei, Kun; Lang, Meidong

    2016-09-01

    Drug-eluting stents with biodegradable polymers as reservoirs have shown great potential in the application of interventional therapy due to their capability of local drug delivery. Herein, poly(l-lactide-co-ε-caprolactone) (PLCL) with three different compositions as carriers for ciprofloxacin lactate (CIP) was coated on ureteral stents by the dipping method. To simulate a body environment, degradation behavior of PLCL as both the bulk film and the stent coating was evaluated in artificial urine (AU, pH6.20) respectively at 37°C for 120days by tracing their weight/Mn loss, water absorption and surface morphologies. Furthermore, the release profile of the eluting drug CIP on each stent exhibited a three-stage pattern, which was greatly affected by the degradation behavior of PLCL except for the burst stage. Interestingly, the degradation results on both macroscopic and molecular level indicated that the release mechanism at stage I was mainly controlled by chain scission instead of the weight loss or morphological changes of the coatings. While for stage II, the release profile was dominated by erosion resulting from the hydrolysis reaction autocatalyzed by acidic degradation residues. In addition, ciprofloxacin-loaded coatings displayed a significant bacterial resistance against E. coli and S. aureus without obvious cytotoxicity to Human foreskin fibroblasts (HFFs). Our results suggested that PLCL copolymers with tunable degradation rate as carriers for ciprofloxacin lactate could be used as a promising long-term antibacterial coating for ureteral stents.

  3. Effect of energetic materials wettability on their outdoor effective elution rate.

    PubMed

    Lapointe, Marie-Claude; Martel, Richard; Lange, Sébastien F; Coté, Sébastien

    2016-07-01

    Energetic materials (EM) contained in military ammunitions have been found in the surface soil and water of training areas and may potentially represent a threat to human health and the environment. EM wettability is an essential physical parameter to characterize because it controls EM dissolution rate. This paper was conducted to determine the wettability of conventional and new EM formulations used in military ammunition. Wettability was estimated in the laboratory via contact angle measurements of water droplets on different EM surfaces. Results show that 2,4,6-trinitrotoluene (TNT), 1,3,5-trinitro-1,3,5-triazinane (RDX), Octol and energetic thermoplastic elastomer (ETPE) 1000 are hydrophilic while Composition B, XRT, GIM, CX-85, ETPE 2000, and C4 are hydrophobic whereas HELOVA gun propellant has a mixed wettability oscillating between hydrophilic and hydrophobic. The present study demonstrates that wettability of EM formulation is generally controlled by their matrix constituents. Results indicate that hydrophobic formulations have a much slower outdoor environmental effective elution rate than hydrophilic ones, with the exception of the hydrophobic C4 formulation whose elution rate is extremely high. The addition of hydrophobic components into EM formulations is recommended to diminish the environmental impact on water, as it has already been done with XRT, GIM and CX-85 formulations. PMID:26985872

  4. Characterizing and modeling of extensive atrazine elution tailing for stable manure-amended agricultural soil.

    PubMed

    Akyol, Nihat Hakan

    2015-01-01

    Non-ideal sorption and extensive elution tailing behavior of atrazine was evaluated for an agricultural soil with and without stable manure amendment (10% by weight). A series of laboratory experiments showed that the sorption of atrazine was described by rate-limited, nonlinear reversible processes (Freundlich isotherm) for both non-amended and amended soil. Non-ideal transport of atrazine exhibited extensive low concentration elution tailing due to the most likely organic carbon fraction in the soil. This tailing behavior was more pronounced and extensive for soil with 10% stable-manure amendment. Two-site transport modeling analyses including non-linear sorption and rate-limited sorption-desorption provided a reasonably good match to the atrazine breakthrough curves but were unable to match the long-term concentration tailing, even for non-amended soil. A mathematical model incorporating nonlinear, rate-limited sorption/desorption described by a continuous-distribution function was used to successfully simulate atrazine transport early-time breakthrough and long-term concentration tailing for both non-amended and amended soil conditions.

  5. Centrifugal partition chromatography elution gradient for isolation of sesquiterpene lactones and flavonoids from Anvillea radiata.

    PubMed

    Destandau, Emilie; Boukhris, Meryem Alaoui; Zubrzycki, Sandrine; Akssira, Mohamed; Rhaffari, Lhoucine El; Elfakir, Claire

    2015-03-15

    An innovative procedure coupling pressurized solvent extraction and centrifugal partition chromatography (CPC) used in linear gradient elution mode was developed to isolate two pure germacranolides (9α-hydroxyparthenolide and 9β-hydroxyparthenolide) and to separate flavonoids (nepetin, isorhamnetin and jaceosidin) and chlorophyll pigments from aerial parts of Anvillea radiata (Coss.&Durieu). The two main germacranolides recovered using this method represent 2 and 5% of the dried plant material respectively. These molecules were extracted using accelerated solvent extraction with chloroform. After optimization of the CPC method, a two-phase solvent system composed of heptane/ethyl acetate/methanol/water (1:5:1:5 v/v/v/v) was employed in descending mode to isolate the germacranolides. Then the lower phase of a heptane/ethyl acetate/methanol/water (6:5:6:5 v/v/v/v) system was pumped in descending mode to generate a linear elution gradient, progressively decreasing the mobile phase polarity, that enabled the flavonoid compounds to be separated in the same run. The efficiency of the preparative separation was controlled through RP-HPLC analysis of the obtained fractions using UV, evaporative light scattering and mass spectrometry detection. The structural identification of the two germacranolides purified over 99% was established by (1)H NMR and (13)C NMR. The least abundant flavonoids were identified by mass spectrometry. PMID:25647341

  6. Evaluation of the Effectiveness of Surfactants and Denaturants to Elute and Denature Adsorbed Protein on Different Surface Chemistries.

    PubMed

    Thyparambil, Aby A; Wei, Yang; Latour, Robert A

    2015-11-01

    The elution and/or denaturation of proteins from material surfaces by chemical excipients such as surfactants and denaturants is important for numerous applications including medical implant reprocessing, bioanalyses, and biodefense. The objective of this study was to develop and apply methods to quantitatively assess how surface chemistry and adsorption conditions influence the effectiveness of three commonly used surfactants (sodium dodecyl sulfate, n-octyl-β-d-glucoside, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) and two denaturants (guanidium hydrochloride and urea) to elute protein (hen egg white lysozyme and bovine pancreatic ribonuclease A) from three different surface chemistries (silica glass, poly(methyl methacrylate), and high-density polyethylene). The structure and bioactivity of residual protein on the surface following elution were characterized using circular dichroism spectropolarimetry and enzyme assays to assess the extent of protein denaturation. Our results indicate that the denaturants were generally more effective than the surfactants in removing the adsorbed proteins from each type of surface. Also, the denaturing capacity of these excipients on the residual proteins on the surfaces was distinctly different from their influence on the proteins in solution and was unique for each of the adsorption conditions. Taken altogether, these results reveal that the effectiveness of surfactants and denaturants to elute and denature adsorbed protein is significantly influenced by surface chemistry and the conditions from which the protein was adsorbed. These results provide a basis for the selection, design, and further development of chemical agents for protein elution and surface decontamination.

  7. Evaluation of the Effectiveness of Surfactants and Denaturants to Elute and Denature Adsorbed Protein on Different Surface Chemistries.

    PubMed

    Thyparambil, Aby A; Wei, Yang; Latour, Robert A

    2015-11-01

    The elution and/or denaturation of proteins from material surfaces by chemical excipients such as surfactants and denaturants is important for numerous applications including medical implant reprocessing, bioanalyses, and biodefense. The objective of this study was to develop and apply methods to quantitatively assess how surface chemistry and adsorption conditions influence the effectiveness of three commonly used surfactants (sodium dodecyl sulfate, n-octyl-β-d-glucoside, and 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate) and two denaturants (guanidium hydrochloride and urea) to elute protein (hen egg white lysozyme and bovine pancreatic ribonuclease A) from three different surface chemistries (silica glass, poly(methyl methacrylate), and high-density polyethylene). The structure and bioactivity of residual protein on the surface following elution were characterized using circular dichroism spectropolarimetry and enzyme assays to assess the extent of protein denaturation. Our results indicate that the denaturants were generally more effective than the surfactants in removing the adsorbed proteins from each type of surface. Also, the denaturing capacity of these excipients on the residual proteins on the surfaces was distinctly different from their influence on the proteins in solution and was unique for each of the adsorption conditions. Taken altogether, these results reveal that the effectiveness of surfactants and denaturants to elute and denature adsorbed protein is significantly influenced by surface chemistry and the conditions from which the protein was adsorbed. These results provide a basis for the selection, design, and further development of chemical agents for protein elution and surface decontamination. PMID:26449787

  8. [Two steps elution method FI on-line adsorption and preconcentration coupled with FAAS for the determination of trace zinc].

    PubMed

    Wang, Zhong-yuan; Zhang, Hong-kang; Fang, Hong-da; Su, Yao-dong; Mittal, Gauri S

    2011-12-01

    A flow injection two steps elution method on-line sorption and preconcentration system coupled to flame atomic absorption spectrometry (FAAS) was developed for the determination of trace Zn in water samples. The conventional elution procedure was divided into two steps: elution procedure and detection procedure. During the elution procedure, the eluent was pumped into KR by the suction of the peristaltic pump and through PTFE tube instead of peristaltic pump tube. By the new method, the dispersion of the analyte was decreased notably, and high absorbance peak value was achieved. Because the eluent was not through the peristaltic pump tube, the peristaltic pump tube was protected from being eroded. Emptying procedure was added in order to insure the veracity and repeatability of the experiment of every time. With 60 s (sample throughput of 37 x h(-1)) of sampling at a flow rate of 6.0 mL x min(-1), an enhancement factor (EF) of 28 (higher than 9 achieved by conventional elution method) and a detection limit (3sigma) of 0.35 x L(-1) were obtained. The precision (RSD, n=11) was 2.1% at the 20 microg x L(-1) level. When 0.1% phi triethannolamine was used as masking reagent, the recovery rate was from 98.7% to 99.6%.

  9. Comparison of the Efficacy of Everolimus-Eluting Stents Versus Drug-Eluting Balloons in Patients With In-Stent Restenosis (from the RIBS IV and V Randomized Clinical Trials).

    PubMed

    Alfonso, Fernando; Pérez-Vizcayno, María José; García Del Blanco, Bruno; García-Touchard, Arturo; Masotti, Mónica; López-Minguez, José R; Iñiguez, Andrés; Zueco, Javier; Velazquez, Maite; Cequier, Angel; Lázaro-García, Rosa; Martí, Vicens; Moris, César; Urbano-Carrillo, Cristobal; Bastante, Teresa; Rivero, Fernando; Cárdenas, Alberto; Gonzalo, Nieves; Jiménez-Quevedo, Pilar; Fernández, Cristina

    2016-02-15

    Treatment of patients with in-stent restenosis (ISR) remains a challenge. This study sought to compare the efficacy of everolimus-eluting stents (EESs) and drug-eluting balloons (DEBs) with paclitaxel in patients with ISR. A pooled analysis of the Restenosis Intra-Stent of Drug-Eluting Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent (RIBS IV) and Restenosis Intra-Stent of Bare-Metal Stents: Drug-Eluting Balloon vs Everolimus-Eluting Stent (RIBS V) randomized trials was performed using patient-level data. In both trials, EESs were compared with DEBs in patients with ISR (RIBS V included 189 patients with bare-metal ISR; RIBS IV included 309 patients with drug-eluting ISR). Inclusion and exclusion criteria were identical in both trials. A total of 249 patients were allocated to EES and 249 to DEB. Clinical follow-up at 1 year was obtained in all (100%) patients and late angiography (median 249 days) in 91% of eligible patients. Compared with patients treated with DEBs, patients treated with EESs obtained better short-term results (postprocedural minimal lumen diameter 2.28 ± 0.5 vs 2.12 ± 0.4 mm, p <0.0001). At follow-up, patients treated with EESs had larger in-segment minimal lumen diameter (primary end point 2.16 ± 0.7 vs 1.88 ± 0.6 mm, p <0.0001; absolute mean difference 0.28 mm; 95% confidence interval [CI] 0.16 to 0.40) and net lumen gain (1.33 ± 0.6 vs 1.00 ± 0.7 mm, p <0.0001) and had lower %diameter stenosis (19 ± 21% vs 28 ± 22%, p <0.0001) and binary restenosis rate (8.7% vs 15.7%, p = 0.02). Consistent results were observed in the in-lesion analysis. No interactions were found between the underlying stent type and treatment effects. At 1-year clinical follow-up, the composite of cardiac death, myocardial infarction, and target vessel revascularization was significantly reduced in the EES arm (8.8% vs 14.5%, p = 0.03; hazard ratio 0.59, 95% CI 0.31 to 0.94) mainly driven by a lower need for target vessel revascularization (6% vs 12.4%, p

  10. Lighting Utilization.

    ERIC Educational Resources Information Center

    Crank, Ron

    This instructional unit is one of 10 developed by students on various energy-related areas that deals specifically with lighting utilization. Its objective is for the student to be able to outline the development of lighting use and conservation and identify major types and operating characteristics of lamps used in electric lighting. Some topics…

  11. Local Release of Antibiotics for Surgical Site Infection Management Using High-Purity Calcium Sulfate: An In Vitro Elution Study

    PubMed Central

    Cooper, John J.; Florance, Hannah; Robinson, Matthew T.; Michell, Stephen

    2015-01-01

    Abstract Background: The aim of this study was to characterize the elution of four antibiotics from pharmaceutical-grade calcium sulfate beads and show that the eluted antibiotics retained efficacy. Methods: Calcium sulfate was combined with gentamicin, tobramycin, vancomycin, or rifampicin (ratio: 20 g of calcium sulfate, to 240 mg, 500 mg, 900 mg, and 600 mg of antibiotic, respectively). Three grams of beads were immersed in 4 mL of sterile phosphate-buffered saline (PBS) at 37°C. At each time point (4, 8, 24 h; 2, 7, 14, 28, 42 d), eluates were removed for analysis by liquid chromatography–mass spectrometry. The antimicrobial efficacy of antibiotics combined with calcium sulfate beads after 42 d was tested by a modified Kirby-Bauer disc diffusion assay. Results: All samples showed a generally exponential decay in the eluted antibiotic concentration. At the first time point, both gentamicin and tobramycin had eluted to a peak concentration of approximately 10,000 mcg/mL. For rifampicin, the peak concentration occurred at 24 h, whereas for vancomycin, it occurred at 48 h. The eluted concentrations exceeded the minimum inhibitory concentration for common periprosthetic joint infection pathogens for the entire span of the 42 study days. Mass spectrometry confirmed all antibiotics were unchanged when eluted from the calcium sulfate carrier. Antimicrobial efficacy was unaltered after 42 d in combination with calcium sulfate at 37°C. Conclusions: Pharmaceutical-grade calcium sulfate has the potential for targeted local release of tobramycin, gentamicin, vancomycin, and rifampicin over a clinically meaningful time period. PMID:25148101

  12. An automated alkaline elution system: DNA damage induced by 1,2-dibromo-3-chloropropane in vivo and in vitro.

    PubMed

    Brunborg, G; Holme, J A; Søderlund, E J; Omichinski, J G; Dybing, E

    1988-11-01

    An automated alkaline elution system for the detection of DNA damage has been developed. After manual application of samples, which is completed within 5 min, the subsequent supply of liquids, changes in flow rates, and temperature are controlled automatically. The system operates 16 filters and may easily be expanded. The sensitivity of the fluorometric DNA determinations with the Hoechst 33258 dye is increased by using an elution buffer (20 mM Na2EDTA, pH 12.50) with low background fluorescence. DNA is determined using an automated setup similar to the one recently presented by Sterzel et al. (1985, Anal. Biochem. 147, 462-467). The most significant modification is the use of a neutralization buffer which allows variations in the pH of eluted fractions. This change increases the sensitivity of the DNA measurements. The automated alkaline elution system was evaluated using the nematocide 1,2-dibromo-3-chloropropane (DBCP) in a study of its genotoxic effects in the testes and the kidneys. Significant DNA damage was induced in testicular cells by 2.5 microM DBCP (1 h) in vitro and 85 mumol/kg DBCP ip (3 h) in vivo. The damage appeared after short treatment times (10 min in vivo). Variations in the observed DBCP response in vivo were largely due to interanimal variations. The automated alkaline elution system proved to be a sensitive assay also for the detection of DNA damage in kidney nuclei prepared from rats exposed to DBCP. Provided that kidney nuclei from untreated rats, mice, or hamster were kept ice-cold until lysing, 85-100% of their DNA was retained after 16 h of elution, indicating highly intact DNA. Under the same conditions, guinea pig DNA was rapidly degraded unless the nuclei were prepared in a buffer with a higher concentration of Na2EDTA (20 mM). PMID:3239754

  13. Transcatheter Arterial Chemoembolization for Liver Cancer: Is It Time to Distinguish Conventional from Drug-Eluting Chemoembolization?

    SciTech Connect

    Liapi, Eleni; Geschwind, Jean-Francois H.

    2011-02-15

    Conventional transcatheter arterial chemoembolization and chemoembolization with drug-eluting beads are increasingly being performed interchangeably in many institutions throughout the world. As both therapies continue to being tested in many phase II and III studies and in combination with other therapies, especially targeted agents, for treatment of primary and metastatic liver cancer, it is imperative to review their current status and evaluate their impact on patient survival. This review critically assesses patient selection, indications, contraindications, techniques, materials, safety, and clinical outcomes of patients treated with conventional chemoembolization and chemoembolization with drug-eluting beads.

  14. Silica xerogel-chitosan nano-hybrids for use as drug eluting bone replacement.

    PubMed

    Lee, Eun-Jung; Jun, Shin-Hee; Kim, Hyoun-Ee; Kim, Hae-Won; Koh, Young-Hag; Jang, Jun-Hyeog

    2010-01-01

    Silica xerogel-chitosan hybrids containing vancomycin were fabricated by the sol-gel process at room temperature and their potential as a drug eluting bone replacement was evaluated in terms of their mechanical properties and drug release behaviors. Regardless of the content of chitosan, all of the prepared hybrids had a uniform mesoporous structure, which would allow the effectual loading of vancomycin. As the content of chitosan was increased, the strength, strain to failure, and work of fracture of the hybrids were significantly enhanced, while the elastic modulus was decreased. These changes in the mechanical properties were mainly attributed to the mitigation of the brittleness of the silica xerogel through its hybridization with the flexible chitosan phase. In addition, the initial burst-effect was remarkably reduced by increasing the content of chitosan. The hybrids with more than 30% chitosan could release the vancomycin for an extended period of time in a controlled manner.

  15. Coronary Stent Thrombosis: Current Insights into New Drug-Eluting Stent Designs

    PubMed Central

    Kim, Hyun Kuk

    2012-01-01

    The advances of interventional cardiology have been achieved by new device development, finding appropriate drug regimes, and understanding of pathomechanism. Drug-eluting stents (DES) implantation with dual anti-platelet therapy reduced revascularization without increasing mortality or myocardial infarction compared with bare-metal stenting. However, late-term stent thrombosis (ST) and restenosis limited its value and raised the safety concern. Main mechanisms of this phenomenon are impaired endothelialization and hypersensitivity reaction with polymer. The second generation DES further improved safety and/or efficacy by using thinner stent strut and biocompatible polymer. Recently, new concept DES with biodegradable polymer, polymer-free and bioabsorbable scaffold are under investigation in the quest to minimize the risk of ST. PMID:23323218

  16. Refractory coronary vasospasm following drug-eluting stent placement treated with cyproheptadine.

    PubMed

    El-Bialy, Adel; Shenoda, Michael; Caraang, Chris

    2006-02-01

    Serotonin (5-hydroxytryptamine) has been recently shown to be an important mediator of coronary vasospasm. Its divergent effect on normal and atherosclerosed arteries has been demonstrated in both animal and human studies. We present a case of coronary vasospasm in a 55-year-old man with repeated episodes of chest pain following coronary percutaneous intervention. Repeat angiography demonstrated no reocclusion or complication. The patient's symptoms were resistant to treatment with maximum doses of two calcium channel antagonists and oral and intravenous nitrates, but responded to cyproheptadine, a nonselective serotonin antagonist. Currently, there are only two reported cases of coronary vasospasm following balloon angioplasty responding to treatment with serotonin antagonists. This is the first case reported case following drug-eluting stent deployment.

  17. Drug-Eluting Nasal Implants: Formulation, Characterization, Clinical Applications and Challenges

    PubMed Central

    Parikh, Ankit; Anand, Utkarshini; Ugwu, Malachy C.; Feridooni, Tiam; Massoud, Emad; Agu, Remigius U.

    2014-01-01

    Chronic inflammation and infection of the nasal sinuses, also referred to as Chronic Rhinosinusitis (CRS), severely affects patients’ quality of life. Adhesions, ostial stenosis, infection and inflammation relapses complicate chronic sinusitis treatment strategies. Drug-eluting stents, packings or implants have been suggested as reasonable alternatives for addressing these concerns. This article reviewed potential drug candidates for nasal implants, formulation methods/optimization and characterization methods. Clinical applications and important considerations were also addressed. Clinically-approved implants (Propel™ implant, the Relieva stratus™ MicroFlow spacer, and the Sinu-Foam™ spacer) for CRS treatment was an important focus. The advantages and limitations, as well as future considerations, challenges and the need for additional research in the field of nasal drug implant development, were discussed. PMID:24871904

  18. Coronary artery bypass is superior to drug-eluting stents in multivessel coronary artery disease.

    PubMed

    Guyton, Robert A

    2006-06-01

    Percutaneous intervention for the treatment of multivessel coronary artery disease continues to displace coronary artery bypass graft surgery. But controlled trials of percutaneous intervention versus coronary bypass, in meta-analysis, have shown a significant survival advantage for coronary bypass. Studies of bare metal stents have not presented any data to prompt reversal of this conclusion for all but the small portion of patients most suited for stenting. Drug-eluting stents have no survival advantage compared with bare metal stents. Data from real-world registries have shown that the current therapy of multivessel disease patients has resulted in a relative excess mortality of as much as 46% in patients with initial stenting compared with patients with initial coronary bypass. Ethical considerations demand that patients with multivessel disease be informed of the documented mortality benefit of coronary bypass graft surgery.

  19. MRI visible drug eluting magnetic microspheres for transcatheter intra-arterial delivery to liver tumors.

    PubMed

    Kim, Dong-Hyun; Chen, Jeane; Omary, Reed A; Larson, Andrew C

    2015-01-01

    Magnetic resonance imaging (MRI)-visible amonafide-eluting alginate microspheres were developed for targeted arterial-infusion chemotherapy. These alginate microspheres were synthesized using a highly efficient microfluidic gelation process. The microspheres included magnetic clusters formed by USPIO nanoparticles to permit MRI and a sustained drug-release profile. The biocompatibility, MR imaging properties and amonafide release kinetics of these microspheres were investigated during in vitro studies. A xenograft rodent model was used to demonstrate the feasibility to deliver these microspheres to liver tumors using hepatic transcatheter intra-arterial infusions and potential to visualize the intra-hepatic delivery of these microspheres to both liver tumor and normal tissues with MRI immediately after infusion. This approach offer the potential for catheter-directed drug delivery to liver tumors for reduced systemic toxicity and superior therapeutic outcomes.

  20. Use of paclitaxel-eluting balloons for endotherapy of anastomotic strictures following liver transplantation.

    PubMed

    Kabar, I; Cicinnati, V R; Beckebaum, S; Cordesmeyer, S; Avsar, Y; Reinecke, H; Schmidt, H H

    2012-12-01

    Biliary anastomotic strictures after liver transplantation are a major source of morbidity and graft failure; however, repeated endoscopic therapy has shown variable long-term success rates. Thus the aim of this prospective case series was to evaluate the safety and efficacy of using paclitaxel-eluting balloons in 13 patients requiring treatment for symptomatic anastomotic strictures following liver transplantation. Sustained clinical success-defined as no need for further endoscopic intervention for at least 6 months - was achieved in 12 /13 patients (92 %). One, two, and three interventions were required in 9 (69 %), 1, and 2 patients, respectively (mean number of sessions was 1.46). Mean (± SD) bilirubin level dropped from 6.8 (± 4.1) mg/dL to 1.4 (± 0.9) mg/dL. These promising results justify carrying out a randomized comparative trial to confirm this innovative approach. PMID:23188664

  1. Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants.

    PubMed

    Cox, Sophie C; Jamshidi, Parastoo; Eisenstein, Neil M; Webber, Mark A; Hassanin, Hany; Attallah, Moataz M; Shepherd, Duncan E T; Addison, Owen; Grover, Liam M

    2016-07-01

    Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8±0.7MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6hour period (<28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16μg/mL) and Staphylococcus epidermidis (1μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections.

  2. DMSO inhibits human platelet activation through cyclooxygenase-1 inhibition. A novel agent for drug eluting stents?

    SciTech Connect

    Asmis, Lars; Tanner, Felix C.; Sudano, Isabella; Luescher, Thomas F.; Camici, Giovanni G.

    2010-01-22

    Background: DMSO is routinely infused together with hematopoietic cells in patients undergoing myeloablative therapy and was recently found to inhibit smooth muscle cells proliferation and arterial thrombus formation in the mouse by preventing tissue factor (TF), a key activator of the coagulation cascade. This study was designed to investigate whether DMSO prevents platelet activation and thus, whether it may represent an interesting agent to be used on drug eluting stents. Methods and results: Human venous blood from healthy volunteers was collected in citrated tubes and platelet activation was studied by cone and platelet analyzer (CPA) and rapid-platelet-function-assay (RPFA). CPA analysis showed that DMSO-treated platelets exhibit a lower adherence in response to shear stress (-15.54 {+-} 0.9427%, n = 5, P < 0.0001 versus control). Additionally, aggregometry studies revealed that DMSO-treated, arachidonate-stimulated platelets had an increased lag phase (18.0% {+-} 4.031, n = 9, P = 0.0004 versus control) as well as a decreased maximal aggregation (-6.388 {+-} 2.212%, n = 6, P = 0.0162 versus control). Inhibitory action of DMSO could be rescued by exogenous thromboxane A2 and was mediated, at least in part, by COX-1 inhibition. Conclusions: Clinically relevant concentrations of DMSO impair platelet activation by a thromboxane A2-dependent, COX-1-mediated effect. This finding may be crucial for the previously reported anti-thrombotic property displayed by DMSO. Our findings support a role for DMSO as a novel drug to prevent not only proliferation, but also thrombotic complications of drug eluting stents.

  3. Degree of Conversion and BisGMA, TEGDMA, UDMA Elution from Flowable Bulk Fill Composites

    PubMed Central

    Lempel, Edina; Czibulya, Zsuzsanna; Kovács, Bálint; Szalma, József; Tóth, Ákos; Kunsági-Máté, Sándor; Varga, Zoltán; Böddi, Katalin

    2016-01-01

    The degree of conversion (DC) and the released bisphenol A diglycidyl ether dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) monomers of bulk-fill composites compared to that of conventional flowable ones were assessed using micro-Raman spectroscopy and high performance liquid chromatography (HPLC). Four millimeter-thick samples were prepared from SureFil SDR Flow (SDR), X-tra Base (XB), Filtek Bulk Fill (FBF) and two and four millimeter samples from Filtek Ultimate Flow (FUF). They were measured with micro-Raman spectroscopy to determine the DC% of the top and the bottom surfaces. The amount of released monomers in 75% ethanol extraction media was measured with HPLC. The differences between the top and bottom DC% were significant for each material. The mean DC values were in the following order for the bottom surfaces: SDR_4mm_20s > FUF_2mm_20s > XB_4mm_20s > FBF_4mm_20s > XB_4mm_10s > FBF_4mm_10s > FUF_4mm_20s. The highest rate in the amount of released BisGMA and TEGDMA was found from the 4 mm-thick conventional flowable FUF. Among bulk-fills, FBF showed a twenty times higher amount of eluted UDMA and twice more BisGMA; meanwhile, SDR released a significantly higher amount of TEGDMA. SDR bulk-fill showed significantly higher DC%; meanwhile XB, FBF did not reach the same level DC, as that of the 2 mm-thick conventional composite at the bottom surface. Conventional flowable composites showed a higher rate of monomer elution compared to the bulk-fills, except FBF, which showed a high amount of UDMA release. PMID:27213361

  4. Chemoembolization (TACE) of Unresectable Intrahepatic Cholangiocarcinoma with Slow-Release Doxorubicin-Eluting Beads: Preliminary Results

    SciTech Connect

    Aliberti, Camillo; Benea, Giorgio Tilli, Massimo; Fiorentini, Giammaria

    2008-09-15

    The purpose of this study was to evaluate the safety and efficacy of TACE with microspheres preloaded with doxorubicin in unresectable intrahepatic cholangiocarcinoma (UCH). Twenty patients with UCH were observed; 9 refused, preferring other palliative care or chemotherapy, and 11 agreed to be treated with one or more cycles of DC beads loaded with doxorubicin (100-150 mg) in a TACE procedure between February 2006 and September 2007. A total of 29 individual TACE procedures were performed. Follow-up imaging was performed on all patients before, immediately after, and 4 weeks after each TACE procedure to evaluate the response and need for further treatment. Each patient received i.v hydration, antibiotics, and medications against nausea and pain before TACE. Survival rate was calculated using Kaplan-Meier survival curve. A response rate of 100% followed RECIST criteria was observed. Eight of eleven patients are alive, with a median survival of 13 months. TACE was well tolerated by all patients. One patient developed hepatic abscess requiring antibiotic therapy. No evidence of marrow toxicity has been reported. Only one of nine patients treated with chemotherapy or palliative care is alive (with a median survival of 7 months in this group of patients). In conclusion, we suggest that doxorubicin-eluting beads TACE is a feasible and effective treatment in patients with UCH. Survival seems to be clearly prolonged in the treated group with respect to the palliative group. We consider that doxorubicin-eluting beads TACE of 100-150 mg may be an appropriate palliative therapy for these patients. Further studies are warranted to confirm these interesting preliminary data.

  5. Degree of Conversion and BisGMA, TEGDMA, UDMA Elution from Flowable Bulk Fill Composites.

    PubMed

    Lempel, Edina; Czibulya, Zsuzsanna; Kovács, Bálint; Szalma, József; Tóth, Ákos; Kunsági-Máté, Sándor; Varga, Zoltán; Böddi, Katalin

    2016-01-01

    The degree of conversion (DC) and the released bisphenol A diglycidyl ether dimethacrylate (BisGMA), triethylene glycol dimethacrylate (TEGDMA) and urethane dimethacrylate (UDMA) monomers of bulk-fill composites compared to that of conventional flowable ones were assessed using micro-Raman spectroscopy and high performance liquid chromatography (HPLC). Four millimeter-thick samples were prepared from SureFil SDR Flow (SDR), X-tra Base (XB), Filtek Bulk Fill (FBF) and two and four millimeter samples from Filtek Ultimate Flow (FUF). They were measured with micro-Raman spectroscopy to determine the DC% of the top and the bottom surfaces. The amount of released monomers in 75% ethanol extraction media was measured with HPLC. The differences between the top and bottom DC% were significant for each material. The mean DC values were in the following order for the bottom surfaces: SDR_4mm_20s > FUF_2mm_20s > XB_4mm_20s > FBF_4mm_20s > XB_4mm_10s > FBF_4mm_10s > FUF_4mm_20s. The highest rate in the amount of released BisGMA and TEGDMA was found from the 4 mm-thick conventional flowable FUF. Among bulk-fills, FBF showed a twenty times higher amount of eluted UDMA and twice more BisGMA; meanwhile, SDR released a significantly higher amount of TEGDMA. SDR bulk-fill showed significantly higher DC%; meanwhile XB, FBF did not reach the same level DC, as that of the 2 mm-thick conventional composite at the bottom surface. Conventional flowable composites showed a higher rate of monomer elution compared to the bulk-fills, except FBF, which showed a high amount of UDMA release. PMID:27213361

  6. Ketoprofen-eluting biodegradable ureteral stents by CO2 impregnation: In vitro study.

    PubMed

    Barros, Alexandre A; Oliveira, Carlos; Reis, Rui L; Lima, Estevão; Duarte, Ana Rita C

    2015-11-30

    Ureteral stents are indispensable tools in urologic practice. The main complications associated with ureteral stents are dislocation, infection, pain and encrustation. Biodegradable ureteral stents are one of the most attractive designs with the potential to eliminate several complications associated with the stenting procedure. In this work we hypothesize the impregnation of ketoprofen, by CO2-impregnation in a patented biodegradable ureteral stent previously developed in our group. The biodegradable ureteral stents with each formulation: alginate-based, gellan gum-based were impregnated with ketoprofen and the impregnation conditions tested were 100 bar, 2 h and three different temperatures (35 °C, 40 °C and 50 °C). The impregnation was confirmed by FTIR and DSC demonstrated the amorphization of the drug upon impregnation. The in vitro elution profile in artificial urine solution (AUS) during degradation of a biodegradable ureteral stent loaded with ketoprofen was evaluated. According to the kinetics results these systems have shown to be very promising for the release ketoprofen in the first 72 h, which is the necessary time for anti-inflammatory delivery after the surgical procedure. The in vitro release studied revealed an influence of the temperature on the impregnation yield, with a higher impregnation yield at 40 °C. Higher yields were also obtained for gellan gum-based stents. The non-cytotoxicity characteristic of the developed ketoprofen-eluting biodegradable ureteral stents was evaluated in L929 cell line by MTS assay which demonstrated the feasibility of this product as a medical device.

  7. Stent selection in patients with myocardial infarction: drug eluting, biodegradable polymers or bare metal stents?

    PubMed

    Mieres, Juan; Rodríguez, Alfredo E

    2012-08-01

    Percutaneous coronary intervention (PCI) has been increasingly used in the last years during interventional procedures in patients with acute coronary syndromes (ACS) including ST elevation myocardial infarction (STEMI) and non-ST elevation myocardial infarction (NSTEMI). In patients with either STEMI, NSTEMI, high risk ACS with EKG changes or cardiac enzymes rises; PCI with bare metal stent (BMS) implantation has been associated with a significant improvement in clinical outcome. Therefore, BMS implantation during primary PCI in STEMI has become a standard of practice. With the introduction of drug eluting stents (DESs) in this decade, the use of these new devices instead of BMSs in patients with STEMI has emerged as a rational PCI alternative in this particular subgroup of patients. In spite of the unquestionable benefits of DESs in terms of reduction of restenosis and TVR, specific concerns have arisen with regard to their long-term safety. High incidence of very late stent thrombosis has been described with these devices, and special attention should be paid in patients with unstable coronary lesions, in which plaque composition and remodeling may play a main role in their safety and long-term outcome. Intraluminal thrombus caused by plaque rupture is the most frequent mechanism of STEMI, in which the necrotic core and thin fibrous cap play a major role. In this context, the use of first DESs designs may be futile or even unsafe because delayed healing may further contribute to plaque instability. Adjunctive invasive imaging tools can improve stent deployment and safety outcome in these lesions with intravascular findings of plaque instability. Recently, other players such as new dedicated antithrombotic BMS designs, including selfexpanding stents or drug-eluting coated balloons, are exploring their potential indications in patients with ACS and myocardial infarction. This paper reports and discusses new stent devices and adjunctive pharmacologic agents. It

  8. Drug deposition in coronary arteries with overlapping drug-eluting stents.

    PubMed

    Rikhtegar, Farhad; Edelman, Elazer R; Olgac, Ufuk; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2016-09-28

    Drug-eluting stents are accepted as mainstream endovascular therapy, yet concerns for their safety may be under-appreciated. While failure from restenosis has dropped to below 5%, the risk of stent thrombosis and associated mortality remain relatively high. Further optimization of drug release is required to minimize thrombosis risk while maintaining therapeutic dose. The complex three-dimensional geometry of deployed stents together with the combination of diffusive and advective drug transport render an intuitive understanding of the situation exceedingly difficult. In situations such as this, computational modeling has proven essential, helping define the limits of efficacy, determine the mode and mechanism of drug release, and identify alternatives to avoid toxicity. A particularly challenging conformation is encountered in coronary arteries with overlapping stents. To study hemodynamics and drug deposition in such vessels we combined high-resolution, multi-scale ex vivo computed tomography with a flow and mass transfer computational model. This approach ensures high geometric fidelity and precise, simultaneous calculation of blood flow velocity, shear stress and drug distribution. Our calculations show that drug uptake by the arterial tissue is dependent both on the patterns of flow disruption near the wall, as well as on the relative positioning of drug-eluting struts. Overlapping stent struts lead to localized peaks of drug concentration that may increase the risk of thrombosis. Such peaks could be avoided by anisotropic stent structure or asymmetric drug release designed to yield homogeneous drug distribution along the coronary artery and, at the least, suggest that these issues need to remain in the forefront of consideration in clinical practice. PMID:27432751

  9. Adding functionality with additive manufacturing: Fabrication of titanium-based antibiotic eluting implants.

    PubMed

    Cox, Sophie C; Jamshidi, Parastoo; Eisenstein, Neil M; Webber, Mark A; Hassanin, Hany; Attallah, Moataz M; Shepherd, Duncan E T; Addison, Owen; Grover, Liam M

    2016-07-01

    Additive manufacturing technologies have been utilised in healthcare to create patient-specific implants. This study demonstrates the potential to add new implant functionality by further exploiting the design flexibility of these technologies. Selective laser melting was used to manufacture titanium-based (Ti-6Al-4V) implants containing a reservoir. Pore channels, connecting the implant surface to the reservoir, were incorporated to facilitate antibiotic delivery. An injectable brushite, calcium phosphate cement, was formulated as a carrier vehicle for gentamicin. Incorporation of the antibiotic significantly (p=0.01) improved the compressive strength (5.8±0.7MPa) of the cement compared to non-antibiotic samples. The controlled release of gentamicin sulphate from the calcium phosphate cement injected into the implant reservoir was demonstrated in short term elution studies using ultraviolet-visible spectroscopy. Orientation of the implant pore channels were shown, using micro-computed tomography, to impact design reproducibility and the back-pressure generated during cement injection which ultimately altered porosity. The amount of antibiotic released from all implant designs over a 6hour period (<28% of the total amount) were found to exceed the minimum inhibitory concentrations of Staphylococcus aureus (16μg/mL) and Staphylococcus epidermidis (1μg/mL); two bacterial species commonly associated with periprosthetic infections. Antibacterial efficacy was confirmed against both bacterial cultures using an agar diffusion assay. Interestingly, pore channel orientation was shown to influence the directionality of inhibition zones. Promisingly, this work demonstrates the potential to additively manufacture a titanium-based antibiotic eluting implant, which is an attractive alternative to current treatment strategies of periprosthetic infections. PMID:27127071

  10. Meta-analysis of long-term clinical outcomes of everolimus-eluting stents.

    PubMed

    Toyota, Toshiaki; Shiomi, Hiroki; Morimoto, Takeshi; Kimura, Takeshi

    2015-07-15

    The superiority of everolimus-eluting stents (EES) over sirolimus-eluting stents (SES) for long-term clinical outcomes has not been yet firmly established. We conducted a systematic review and a meta-analysis of randomized controlled trials (RCTs) comparing EES directly with SES using the longest available follow-up data. We searched PubMed, the Cochrane database, and ClinicalTrials.gov for RCTs comparing outcomes between EES and SES and identified 13,434 randomly assigned patients from 14 RCTs. EES was associated with significantly lower risks than SES for definite stent thrombosis (ST), definite/probable ST, target-lesion revascularization (TLR), and major adverse cardiac events (MACE). The risks for all-cause death and myocardial infarction were similar between EES and SES. By the stratified analysis according to the timing after stent implantation, the favorable trend of EES relative to SES for ST, TLR, and MACE was consistently observed both within and beyond 1 year. The lower risk of EES relative to SES for MACE beyond 1 year was statistically significant (pooled odds ratio 0.77, 95% confidence interval 0.61 to 0.96, p = 0.02). In conclusion, the current meta-analysis of 14 RCTs directly comparing EES with SES suggested that EES provided improvement in both safety and efficacy; EES compared with SES was associated with significantly lower risk for definite ST, definite/probable ST, TLR, and MACE. The direction and magnitude of the effect beyond 1 year were comparable with those observed within 1 year.

  11. Simulation of elution profiles for two-dimensional dynamic gas chromatographic experiments.

    PubMed

    Trapp, Oliver; Shellie, Robert; Marriott, Philip; Schurig, Volker

    2003-09-01

    The interconversion of E and Z isomers of acetaldoxime 1 and butyraldoxime 2 have been investigated by comprehensive two-dimensional dynamic gas chromatography (DGCxDGC) and computer simulation. Time-resolved cryogenic modulation is capable of revealing the precise isomeric ratio as a fine structure under the dynamic elution profile, which is characterized in one-dimensional experiments by a plateau formation or peak coalescence caused by interconversion of the isomers during the separation process. The chromatographic theoretical plate model has been extended for the computer simulation of comprehensive two-dimensional dynamic chromatographic experiments. A novel program, ChromWin 2D, based on the new algorithm has been developed for computer simulation to evaluate and predict the elution profiles of DGCxDGC experiments. ChromWin 2D allows the determination of rate constants and barriers of isomerization, epimerization, and enantiomerization processes occurring during chromatographic separations. The Eyring activation parameters of the E/Z and Z/E isomerization barriers in the presence of the stationary phase BP21 (poly(ethylene glycol) terephthalate terminated) were determined by temperature-dependent experiments between 80 and 90 degrees C for 1 and 70 and 130 degrees C for 2. The thermodynamic Gibbs free energy of the E/Z equilibrium of the isomers has been determined from the time-resolved chromatograms by cryogenic modulation. The method described here constitutes a new and important tool for the determination of isomerization barriers, which are of great interest, for example, for the quantitative determination of derivatized aldehydes, such as dinitrophenylhydrazine derivatives, in trace analysis.

  12. Determination of theophylline in serum by molecularly imprinted solid-phase extraction with pulsed elution.

    PubMed

    Mullett, W M; Lai, E P

    1998-09-01

    The technique of molecular imprinting is used to produce an extensively cross-linked poly(methacrylic acid-co-ethylene dimethacrylate) material that contains theophylline as a print molecule. After Soxhlet extraction of the theophylline, binding sites are formed in the polymer with complementary size, shape, and positioning of chemical functionalities. The molecularly imprinted polymer's (MIP) high theophylline selectivity, chemical stability, and physically robust nature make it an ideal stationary-phase material in columns for HPLC separation of theophylline from other structurally related drug compounds. Mobile-phase tests confirm that a retention mechanism typical of normal-phase chromatography governs the separation, and selectivity of the MIP column can be controlled by a combination of the mobile phase and the sample solvent. Under optimal conditions, the MIP column functions like a solid-phase sorbent for theophylline extraction. Rapid elution of the bound theophylline can be accomplished in a pulsed format through injection of 20 μL of a solvent that has the proper polarity and protic nature to disrupt the electrostatic interactions and hydrogen bonding between theophylline and binding sites. A concentration detection limit of 120 ng/mL is obtained using direct UV absorption detection at 270 nm, which corresponds to a mass detection limit of 2.4 ng. This new technique, molecularly imprinted solid-phase extraction with pulsed elution (MISPE-PE), permits on-line preconcentration of theophylline from a large volume of dilute sample solution. Using a sample volume of 300 μL, a 40 ng/mL standard solution produces a detectable peak signal. Application of MISPE-PE in serum analysis further demonstrates the high capability of the MIP column to selectively isolate theophylline from other matrix components for fast, accurate determination.

  13. My Interventional Drug-Eluting Stent Educational App (MyIDEA): Patient-Centered Design Methodology

    PubMed Central

    Shroff, Adhir; Groo, Vicki; Dickens, Carolyn; Field, Jerry; Baumann, Matthew; Welland, Betty; Gutowski, Gerry; Flores Jr, Jose D; Zhao, Zhongsheng; Bahroos, Neil; Hynes, Denise M; Wilkie, Diana J

    2015-01-01

    Background Patient adherence to medication regimens is critical in most chronic disease treatment plans. This study uses a patient-centered tablet app, “My Interventional Drug-Eluting Stent Educational App (MyIDEA).” This is an educational program designed to improve patient medication adherence. Objective Our goal is to describe the design, methodology, limitations, and results of the MyIDEA tablet app. We created a mobile technology-based patient education app to improve dual antiplatelet therapy adherence in patients who underwent a percutaneous coronary intervention and received a drug-eluting stent. Methods Patient advisers were involved in the development process of MyIDEA from the initial wireframe to the final launch of the product. The program was restructured and redesigned based on the patient advisers’ suggestions as well as those from multidisciplinary team members. To accommodate those with low health literacy, we modified the language and employed attractive color schemes to improve ease of use. We assumed that the target patient population may have little to no experience with electronic tablets, and therefore, we designed the interface to be as intuitive as possible. Results The MyIDEA app has been successfully deployed to a low-health-literate elderly patient population in the hospital setting. A total of 6 patients have interacted with MyIDEA for an average of 17.6 minutes/session. Conclusions Including patient advisers in the early phases of a mobile patient education development process is critical. A number of changes in text order, language, and color schemes occurred to improve ease of use. The MyIDEA program has been successfully deployed to a low-health-literate elderly patient population. Leveraging patient advisers throughout the development process helps to ensure implementation success. PMID:26139587

  14. Drug deposition in coronary arteries with overlapping drug-eluting stents.

    PubMed

    Rikhtegar, Farhad; Edelman, Elazer R; Olgac, Ufuk; Poulikakos, Dimos; Kurtcuoglu, Vartan

    2016-09-28

    Drug-eluting stents are accepted as mainstream endovascular therapy, yet concerns for their safety may be under-appreciated. While failure from restenosis has dropped to below 5%, the risk of stent thrombosis and associated mortality remain relatively high. Further optimization of drug release is required to minimize thrombosis risk while maintaining therapeutic dose. The complex three-dimensional geometry of deployed stents together with the combination of diffusive and advective drug transport render an intuitive understanding of the situation exceedingly difficult. In situations such as this, computational modeling has proven essential, helping define the limits of efficacy, determine the mode and mechanism of drug release, and identify alternatives to avoid toxicity. A particularly challenging conformation is encountered in coronary arteries with overlapping stents. To study hemodynamics and drug deposition in such vessels we combined high-resolution, multi-scale ex vivo computed tomography with a flow and mass transfer computational model. This approach ensures high geometric fidelity and precise, simultaneous calculation of blood flow velocity, shear stress and drug distribution. Our calculations show that drug uptake by the arterial tissue is dependent both on the patterns of flow disruption near the wall, as well as on the relative positioning of drug-eluting struts. Overlapping stent struts lead to localized peaks of drug concentration that may increase the risk of thrombosis. Such peaks could be avoided by anisotropic stent structure or asymmetric drug release designed to yield homogeneous drug distribution along the coronary artery and, at the least, suggest that these issues need to remain in the forefront of consideration in clinical practice.

  15. Rapid complement fixation technique for estimating complement-fixing antigen elution profiles of viruses from gel filtration columns.

    PubMed

    Cornesky, R A; Hammon, W M; Sather, G E; Atchison, R

    1972-07-01

    The complement fixation elution profiles of dengue-2 virus-infected suckling mouse brain supernatant fluids from Sephadex G-200 columns were compared by the antigen end-point titration procedure and by a complement dilution technique. The latter technique was found to be a quick method for approximating the complement-fixing antigen in eluates.

  16. Reduction of burn scar formation by halofuginone-eluting silicone gel sheets: a controlled study on nude mice.

    PubMed

    Zeplin, Philip H

    2012-03-01

    Burn scar formations can cause disfiguration and loss of dermal function. The purpose of this study was to examine whether application of modified silicone gel sheets with an antifibrotic drug halofuginone-eluting hybrid surface produce an effect on scar development. There were a total of 2 animal groups. The athymic nude mice (nu/nu) of both groups underwent transplantation of full-thickness human skin grafts onto their backs and setting of partial thickness burn injury. The status of local scar development was observed over a period of 3 months after the application of silicone gel sheets and also after application of surface-modified halofuginone-eluting silicone gel sheets. Subsequently, via real-time polymerase chain reaction, the cDNA levels from key mediators of scar formation (transforming growth factor beta, COL1A1, connective tissue growth factor, fibroblast growth factor 2, matrix metalloproteinase 2, matrix metalloproteinase 9) were established and statistically evaluated. In comparison with uncoated silicone gel sheets, the application of halofuginone-eluting silicone gel sheets lead to a significant difference in gene expression activity in scar tissue. Halofuginone-eluting hybrid surface silicone gel sheets significantly increase the antiscarring effect of adhesive silicone gel sheets by deceleration and downregulation of scar development by normalization of the expression activity.

  17. Separation and determination of rare earth elements by Dowex 2-X8 resin using sodium trimetaphosphate as elution agent.

    PubMed

    Sungur, S K; Akseli, A

    2000-04-01

    The distribution coefficients of rare earth elements and thorium with Dowex 2-X8, 200-400 mesh, a strongly basic anion-exchange resin, have been determined regarding four different concentrations of sodium trimetaphosphate (3 x 10(-3), 5 x 10(-3), 7 x 10(-3) and 0.01 M). The separation of the rare earths and thorium obtained from an Australian monazite has been investigated by anion-exchange chromatography with sodium trimetaphosphate concentration gradient on a Dowex 2-X8 ion-exchange columns. The order of elution of the elements was the reverse of the order of elution of the same elements on Dowex 1 resin. The elution was investigated using 5 mg and 250 mg samples. In the separation of 5 mg samples, all elements were separated in 29 min. It has been seen that the elution peaks are narrow, tailing effects are very small, Dy and Y are well separated. Qualitative and quantitative determinations were realized by spectrofluorometry. PMID:10817370

  18. Sustained Efficacy and Arterial Drug Retention by a Fast Drug Eluting Cross-Linked Fatty Acid Coronary Stent Coating

    PubMed Central

    Artzi, Natalie; Tzafriri, Abraham R.; Faucher, Keith M.; Moodie, Geoffrey; Albergo, Theresa; Conroy, Suzanne; Corbeil, Scott; Martakos, Paul; Virmani, Renu; Edelman, Elazer R.

    2015-01-01

    The long held assumption that sustained drug elution from stent coatings over weeks to months is imperative for clinical efficacy has limited the choice for stent coating materials. We developed and evaluated an omega-3 fatty acid (O3FA) based stent coating that is 85% absorbed and elutes 97% of its Sirolimus analog (Corolimus) load within 8d of implantation. O3FA coated stents sustained drug levels in porcine coronary arteries similarly to those achieved by slow-eluting durable coated Cypher Select Plus Stents and with significantly lower levels of granuloma formation and luminal stenosis. Computational modeling confirmed that diffusion and binding constants of Corolimus and Sirolimus are identical and explained that the sustained retention of Corolimus was facilitated by binding to high affinity intracellular receptors (FKBP12). First in man outcomes were positive—unlike Cypher stents where late lumen loss drops over 6 month, there was a stable effect without diminution in the presence of O3FA. These results speak to a new paradigm whereby the safety of drug eluting stents can be optimized through the use of resorbable biocompatible coating materials with resorption kinetics that coincide with the dissociation and tissue elimination of receptor-bound drug. PMID:26314990

  19. Brachytherapy Application With In Situ Dose Painting Administered by Gold Nanoparticle Eluters

    SciTech Connect

    Sinha, Neeharika; Cifter, Gizem; Sajo, Erno; Kumar, Rajiv; Sridhar, Srinivas; Nguyen, Paul L.; Cormack, Robert A.; Makrigiorgos, G. Mike; Ngwa, Wilfred

    2015-02-01

    Purpose: Recent studies show promise that administering gold nanoparticles (GNP) to tumor cells during brachytherapy could significantly enhance radiation damage to the tumor. A new strategy proposed for sustained administration of the GNP in prostate tumors is to load them into routinely used brachytherapy spacers for customizable in situ release after implantation. This in silico study investigated the intratumor biodistribution and corresponding dose enhancement over time due to GNP released from such GNP-loaded brachytherapy spacers (GBS). Method and Materials: An experimentally determined intratumoral diffusion coefficient (D) for 10-nm nanoparticles was used to estimate D for other sizes by using the Stokes-Einstein equation. GNP concentration profiles, obtained using D, were then used to calculate the corresponding dose enhancement factor (DEF) for each tumor voxel, using dose painting-by-numbers approach, for times relevant to the considered brachytherapy sources' lifetimes. The investigation was carried out as a function of GNP size for the clinically applicable low-dose-rate brachytherapy sources iodine-125 (I-125), palladium-103 (Pd-103), and cesium-131 (Cs-131). Results: Results showed that dose enhancement to tumor voxels and subvolumes during brachytherapy can be customized by varying the size of GNP released or eluted from the GBS. For example, using a concentration of 7 mg/g GNP, significant DEF (>20%) could be achieved 5 mm from a GBS after 5, 12, 25, 46, 72, 120, and 195 days, respectively, for GNP sizes of 2, 5, 10, 20, 30, and 50 nm and for 80 nm when treating with I-125. Conclusions: Analyses showed that using Cs-131 provides the highest dose enhancement to tumor voxels. However, given its relatively longer half-life, I-125 presents the most flexibility for customizing the dose enhancement as a function of GNP size. These findings provide a useful reference for further work toward development of potential new brachytherapy application with

  20. A randomized, prospective, intercontinental evaluation of a bioresorbable polymer sirolimus-eluting coronary stent system: the CENTURY II (Clinical Evaluation of New Terumo Drug-Eluting Coronary Stent System in the Treatment of Patients with Coronary Artery Disease) trial

    PubMed Central

    Saito, Shigeru; Valdes-Chavarri, Mariano; Richardt, Gert; Moreno, Raul; Iniguez Romo, Andrés; Barbato, Emanuele; Carrie, Didier; Ando, Kenji; Merkely, Bela; Kornowski, Ran; Eltchaninoff, Hélène; James, Stefan; Wijns, William

    2014-01-01

    Aim The aim of this study was to establish safety and efficacy of a new sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES). Sirolimus-eluting stent with bioresorbable polymer was compared with everolimus-eluting, permanent polymer, Xience stent (PP-EES) in the frame of a CENTURY II clinical trial designed to make global clinical data compliant with regulatory requirements in Europe and Japan. Methods and results The CENTURY II is a prospective, multicentre, randomized (1 : 1), single blind, controlled, non-inferiority clinical trial conducted at 58 study sites in Japan, Europe, and Korea. A total of 1123 patients requiring a percutaneous coronary intervention (PCI) procedure, with implantation of drug-eluting stent (DES), were enrolled [total population (TP)]. Randomization of patients was stratified for the subset of patients matching requirements for DES in Japan (Cohort JR, n = 722). Baseline patient demographic and angiographic characteristics were similar in both study arms, with minimal differences between the TP and Cohort JR. The primary endpoint, freedom from target lesion failure (TLF) at 9 months—TLF [composite of cardiac death, target-vessel-related myocardial infarction (MI) and target lesion revascularization]—was 95.6% with BP-SES and 95.1% with PP-EES (Pnon-inferiority<0.0001). Composite of cardiac death and MI rate was 2.9 and 3.8% (P = 0.40) and target vessel revascularization was 4.5% with BP-SES and 4.2% with PP-EES (P = 0.77). The stent thrombosis rate was 0.9% in both arms. In Cohort JR, freedom from TLF was 95.9 and 94.6% (Pnon-inferiority < 0.0005) with BP-SES and PP-EES, respectively. Conclusion The new bioresorbable polymer sirolimus-eluting stent showed safety and efficacy profiles similar to durable polymer everolimus-eluting stent at 9-month follow-up. Study registration number UMIN000006940. PMID:24847155

  1. A randomized multicenter comparison of hybrid sirolimus-eluting stents with bioresorbable polymer versus everolimus-eluting stents with durable polymer in total coronary occlusion: rationale and design of the Primary Stenting of Occluded Native Coronary Arteries IV study

    PubMed Central

    2012-01-01

    Background Percutaneous recanalization of total coronary occlusion (TCO) was historically hampered by high rates of restenosis and reocclusions. The PRISON II trial demonstrated a significant restenosis reduction in patients treated with sirolimus-eluting stents compared with bare metal stents for TCO. Similar reductions in restenosis were observed with the second-generation zotarolimus-eluting stent and everolimus-eluting stent. Despite favorable anti-restenotic efficacy, safety concerns evolved after identifying an increased rate of very late stent thrombosis (VLST) with drug-eluting stents (DES) for the treatment of TCO. Late malapposition caused by hypersensitivity reactions and chronic inflammation was suggested as a probable cause of these VLST. New DES with bioresorbable polymer coatings were developed to address these safety concerns. No randomized trials have evaluated the efficacy and safety of the new-generation DES with bioresorbable polymers in patients treated for TCO. Methods/Design The prospective, randomized, single-blinded, multicenter, non-inferiority PRISON IV trial was designed to evaluate the safety, efficacy, and angiographic outcome of hybrid sirolimus-eluting stents with bioresorbable polymers (Orsiro; Biotronik, Berlin, Germany) compared with everolimus-eluting stents with durable polymers (Xience Prime/Xpedition; Abbott Vascular, Santa Clara, CA, USA) in patients with successfully recanalized TCOs. In total, 330 patients have been randomly allocated to each treatment arm. Patients are eligible with estimated duration of TCO ≥4 weeks with evidence of ischemia in the supply area of the TCO. The primary endpoint is in-segment late luminal loss at 9-month follow-up angiography. Secondary angiographic endpoints include in-stent late luminal loss, minimal luminal diameter, percentage of diameter stenosis, in-stent and in-segment binary restenosis and reocclusions at 9-month follow-up. Additionally, optical coherence tomography is performed in

  2. Antiplatelet therapy discontinuation following drug-eluting stent placement: dangers, reasons, and management recommendations.

    PubMed

    Moussa, Issam D; Colombo, Antonio

    2009-12-01

    Drug-eluting stents (DES) have several advantages over bare-metal stents (BMS), including significantly lower target vessel revascularization. However, DES is associated with a higher incidence of late stent thrombosis (ST). Although late ST after DES placement is uncommon (approximately 0.4-0.6%/year), it is catastrophic clinical consequences make it a concern. Dual antiplatelet therapy (DAT) with aspirin and clopidogrel is the standard of care for prevention of ST, and DAT discontinuation is associated with a marked increase in ST risk. These guidelines recommend continuing DAT for > or = 12 months after DES implantation in patients not at high risk for bleeding. Premature DAT discontinuation is common in clinical practice. Therefore, it is imperative that physicians be aware of factors contributing to discontinuation, including cost, patient education, and actual bleeding events, so as to educate their patients about the risks and benefits of continued DAT. This review highlights the risks of premature DAT discontinuation, discusses common reasons for discontinuation, and offers potential solutions to improve adherence.

  3. Electrospun Polymeric Core-sheath Yarns as Drug Eluting Surgical Sutures.

    PubMed

    Padmakumar, Smrithi; Joseph, John; Neppalli, Madhuri Harsha; Mathew, Sumi Elizabeth; Nair, Shantikumar V; Shankarappa, Sahadev A; Menon, Deepthy

    2016-03-23

    Drug-coated sutures are widely used as delivery depots for antibiotics and anti-inflammatory drugs at surgical wound sites. Although drug-laden coating provides good localized drug concentration, variable loading efficiency and release kinetics limits its use. Alternatively, drug incorporation within suture matrices is hampered by the harsh fabrication conditions required for suture-strength enhancement. To circumvent these limitations, we fabricated mechanically robust electrospun core-sheath yarns as sutures, with a central poly-l-lactic acid core, and a drug-eluting poly-lactic-co-glycolic acid sheath. The electrospun sheath was incorporated with aceclofenac or insulin to demonstrate versatility of the suture in loading both chemical and biological class of drugs. Aceclofenac and insulin incorporated sutures exhibited 15% and 4% loading, and release for 10 and 7 days, respectively. Aceclofenac sutures demonstrated reduced epidermal hyperplasia and cellularity in skin-inflammation animal model, while insulin loaded sutures showed enhanced cellular migration in wound healing assay. In conclusion, we demonstrate an innovative strategy of producing mechanically strong, prolonged drug-release sutures loaded with different classes of drugs. PMID:26936629

  4. Extravascular use of drug-eluting beads: A promising approach in compartment-based tumor therapy

    PubMed Central

    Binder, Simon; Lewis, Andrew L; Löhr, J-Matthias; Keese, Michael

    2013-01-01

    Intraperitoneal carcinomatosis (PC) may occur with several tumor entities. The prognosis of patients suffering from PC is usually poor. Present treatment depends on the cancer entity and includes systemic chemotherapy, radiation therapy, hormonal therapy and surgical resection. Only few patients may also benefit from hyperthermic intraperitoneal chemotherapy with a complete tumor remission. These therapies are often accompanied by severe systemic side-effects. One approach to reduce side effects is to target chemotherapeutic agents to the tumor with carrier devices. Promising experimental results have been achieved using drug-eluting beads (DEBs). A series of in vitro and in vitro experiments has been conducted to determine the suitability of their extravascular use. These encapsulation devices were able to harbor CYP2B1 producing cells and to shield them from the hosts immune system when injected intratumorally. In this way ifosfamide - which is transformed into its active metabolites by CYP2B1 - could be successfully targeted into pancreatic tumor growths. Furthermore DEBs can be used to target chemotherapeutics into the abdominal cavity for treatment of PC. If CYP2B1 producing cells are proven to be save for usage in man and if local toxic effects of chemotherapeutics can be controlled, DEBs will become promising tools in compartment-based anticancer treatment. PMID:24282349

  5. Acrylamide elution from roasted barley grains into mugicha and its formation during roasting.

    PubMed

    Mizukami, Yuzo; Yoshida, Mitsuru; Ono, Hiroshi

    2016-01-01

    This paper investigated acrylamide elution from roasted barley grain into mugicha and its formation during roasting of the grain. Mugicha is an infusion of roasted barley grains. Highly water-soluble acrylamide was easily extracted to mugicha from milled roasted barley grains in teabags. On the other hand, the acrylamide concentration in mugicha prepared from loose grain increased with longer simmering and steeping times. During roasting in a drum roaster, the acrylamide concentration of the grain increased as the surface temperature rose, reaching a maximum at 180-240°C. Above this temperature, the acrylamide concentration decreased with continued roasting, exhibiting an inverted 'U'-shaped curve. For most of the samples, the acrylamide concentration showed good correlation with the value of the colour space parameter L*. The dark-coloured roasted barley grains with lower L* values contained lower amounts of acrylamide as a result of deep roasting. The level of asparagine in barley grains was found to be a significant factor related to acrylamide formation in roasted barley products. The data are an important contribution to the mitigation of acrylamide intake from mugicha.

  6. Production of bio-fuel ethanol from distilled grain waste eluted from Chinese spirit making process.

    PubMed

    Tan, Li; Sun, Zhaoyong; Zhang, Wenxue; Tang, Yueqin; Morimura, Shigeru; Kida, Kenji

    2014-10-01

    Distilled grain waste eluted from Chinese spirit making is rich in carbohydrates, and could potentially serve as feedstock for the production of bio-fuel ethanol. Our study evaluated two types of saccharification methods that convert distilled grain waste to monosaccharides: enzymatic saccharification and concentrated H2SO4 saccharification. Results showed that enzymatic saccharification performed unsatisfactorily because of inefficient removal of lignin during pretreatment. Concentrated H2SO4 saccharification led to a total sugar recovery efficiency of 79.0 %, and to considerably higher sugar concentrations than enzymatic saccharification. The process of ethanol production from distilled grain waste based on concentrated H2SO4 saccharification was then studied. The process mainly consisted of concentrated H2SO4 saccharification, solid-liquid separation, decoloration, sugar-acid separation, oligosaccharide hydrolysis, and continuous ethanol fermentation. An improved simulated moving bed system was employed to separate sugars from acid after concentrated H2SO4 saccharification, by which 95.8 % of glucose and 85.8 % of xylose went into the sugar-rich fraction, while 83.3 % of H2SO4 went into the acid-rich fraction. A flocculating yeast strain, Saccharomyces cerevisiae KF-7, was used for continuous ethanol fermentation, which produced an ethanol yield of 91.9-98.9 %, based on glucose concentration.

  7. New aliphatic glycerophosphoryl-containing polyurethanes: synthesis, platelet adhesion and elution cytotoxicity studies.

    PubMed

    Acetti, Daniela; D'Arrigo, Paola; Giordano, Carmen; Macchi, Piero; Servi, Stefano; Tessaro, Davide

    2009-04-01

    in this study new poly(ether)urethanes (PeUs) based on aliphatic diisocyanates were synthesized with phospholipid-like residues as chain extenders. The primary objective was to prepare new polyurethanes from diisocyanates that are less toxic than the aromatic ones widely used in medical-grade polyurethanes, in order to investigate the effect of the different aromatic or aliphatic hard segment content on the final properties of the materials. Some glycerophospho residues were simultaneously introduced to enhance the hemocompatibility of these materials. Polymers were prepared by a conventional two-step solution polymerization procedure using hexamethylene diisocyanate (HDi) and dodecametilendiisocyanate (DDi) and poly(1,4-butanediol) with molecular weight 1000 to form prepolymers, which were subsequently polymerized with 1-glycerophosphorylcholine (1-GPC) or glycerophosphorylserine (GPS) to act as chain extenders. The reference polymers bearing 1,4-butandiol (BD) were also synthesized. The polymers obtained were characterized by fourier transform infrared spectroscopy (fT-iR), nuclear magnetic resonance (1H nmR), and differential scanning calorimetry (DSC). The hemocompatibility of synthesized segmented polyurethanes was preliminarily investigated by platelet-rich plasma contact studies and related scanning electron microscopy (Sem) photographs as well as by cell viability assay after cell exposure to material elutions to assess the effect of any toxic leachables coming out from the samples. Two of the polymers gave interesting results, suggesting the desirability of further investigation into their possible use in biomedical devices. PMID:19569028

  8. Selective doxorubicin drug eluting beads chemoembolization of hypovascular hepatocellular carcinoma using cone beam computed tomography.

    PubMed

    Kalra, Naveen; Mahajan, Divyesh; Chawla, Yogesh; Khandelwal, N

    2012-10-01

    Hepatocellular carcinoma (HCC) of the liver is the third most common cause of cancer-related deaths in the world. Only one-third of patients with HCC are suitable candidates for hepatic resection. Transarterial chemoembolization (TACE) is performed in unresectable HCC. Drug-eluting beads (DEB) TACE is a modification of TACE, in which doxorubicin beads are used as embolizing material. These beads deliver the drug and embolize the vessels; however, it carries the risk of non-target embolization and it is difficult in cases with absent arterial blush on digital subtraction angiography (DSA). This is resolved using C-arm cone-beam computed tomography in the DSA suite. It identifies the tumor-feeding vessels, their area of supply, and differentiates between tumor and normal liver parenchyma. In addition, it is very useful in the embolization of hypovascular HCC. It helps and guides the radiologist in performing TACE effectively and also prevents non-target embolization of normal liver parenchyma. PMID:23833414

  9. CN-GELFrEE - Clear Native Gel-eluted Liquid Fraction Entrapment Electrophoresis.

    PubMed

    Melani, Rafael D; Seckler, Henrique S; Skinner, Owen S; Do Vale, Luis H F; Catherman, Adam D; Havugimana, Pierre C; Valle de Sousa, Marcelo; Domont, Gilberto B; Kelleher, Neil L; Compton, Philip D

    2016-01-01

    Protein complexes perform an array of crucial cellular functions. Elucidating their non-covalent interactions and dynamics is paramount for understanding the role of complexes in biological systems. While the direct characterization of biomolecular assemblies has become increasingly important in recent years, native fractionation techniques that are compatible with downstream analysis techniques, including mass spectrometry, are necessary to further expand these studies. Nevertheless, the field lacks a high-throughput, wide-range, high-recovery separation method for native protein assemblies. Here, we present clear native gel-eluted liquid fraction entrapment electrophoresis (CN-GELFrEE), which is a novel separation modality for non-covalent protein assemblies. CN-GELFrEE separation performance was demonstrated by fractionating complexes extracted from mouse heart. Fractions were collected over 2 hr and displayed discrete bands ranging from ~30 to 500 kDa. A consistent pattern of increasing molecular weight bandwidths was observed, each ranging ~100 kDa. Further, subsequent reanalysis of native fractions via SDS-PAGE showed molecular-weight shifts consistent with the denaturation of protein complexes. Therefore, CN-GELFrEE was proved to offer the ability to perform high-resolution and high-recovery native separations on protein complexes from a large molecular weight range, providing fractions that are compatible with downstream protein analyses. PMID:26967310

  10. A polymer-free Paclitaxel eluting coronary stent: effects of solvents, drug concentrations and coating methods.

    PubMed

    Lamichhane, Sujan; Gallo, Annemarie; Mani, Gopinath

    2014-06-01

    Some polymer coatings used in drug-eluting stents (DES) cause adverse reactions. Hence, the use of self-assembled monolayers (SAMs) as a polymer-free platform to deliver an anti-proliferative drug (paclitaxel-PAT) from 2D metal substrates was previously demonstrated. In this study, we optimized the PAT coating on SAMs coated 3D coronary stents. For the optimization process, we investigated the effects of solvents (ethanol, DMSO, and their mixtures), drug concentrations (2, 3, 4, 8, and 12 mg/mL) in the coating solution, and coating methods (dip and spray) on PAT deposition. A solvent mixture of 75:25 v/v Et-OH:DMSO was determined to be the best for obtaining smooth and homogenous PAT coating. PAT coated stents prepared using 8 mg/mL and 3 mg/mL concentrations of PAT by dip and spray coating methods, respectively, were optimal in terms of carrying adequate drug doses (0.35 µg/mm(2) for dipping and 0.76 µg/mm(2) for spraying) as well as negligible defects observed in the coating. PAT was successfully released from SAMs coated stents in a biphasic manner with an initial burst followed by a sustained release for up to 10 weeks. Thus, this study sheds light on the effects of solvents, drug concentrations, and coating methods on preparing a polymer-free DES. PMID:24705673

  11. Determination of adsorption isotherm parameters for minor whey proteins by gradient elution preparative liquid chromatography.

    PubMed

    Faraji, Naeimeh; Zhang, Yan; Ray, Ajay K

    2015-09-18

    Ion-Exchange Chromatography (IEC) techniques have been extensively investigated in protein purification processes, due to the more selective and milder separation steps. To date, existing studies of minor whey proteins fractionation in IEC have primarily been conducted as batch uptake studies, which require more experimental search space, time and materials. In this work, the selected resin's (SP Sepharose FF) equilibrium and dynamic binding capacity were first investigated. Next, adsorption of the pure binary mixture of lactoperoxidase and lactoferrin was studied to calibrate steric mass action (SMA) model using a simplified approach with data from single column experiments. The calibrated model was then verified by performing factorial-design based experiments for various process operating conditions assessing process performance on a larger bed height column. The model predicted results demonstrated a realistic agreement with the experiments providing reproducible column elution profile and reduced experimental work. Finally, whey protein isolate was used to evaluate model parameters in real conditions. Results obtained herein are suitable for future large scale applications.

  12. Elution profile analysis of SDS-induced subcomplexes by quantitative mass spectrometry.

    PubMed

    Texier, Yves; Toedt, Grischa; Gorza, Matteo; Mans, Dorus A; van Reeuwijk, Jeroen; Horn, Nicola; Willer, Jason; Katsanis, Nicholas; Roepman, Ronald; Gibson, Toby J; Ueffing, Marius; Boldt, Karsten

    2014-05-01

    Analyzing the molecular architecture of native multiprotein complexes via biochemical methods has so far been difficult and error prone. Protein complex isolation by affinity purification can define the protein repertoire of a given complex, yet, it remains difficult to gain knowledge of its substructure or modular composition. Here, we introduce SDS concentration gradient induced decomposition of protein complexes coupled to quantitative mass spectrometry and in silico elution profile distance analysis. By applying this new method to a cellular transport module, the IFT/lebercilin complex, we demonstrate its ability to determine modular composition as well as sensitively detect known and novel complex components. We show that the IFT/lebercilin complex can be separated into at least five submodules, the IFT complex A, the IFT complex B, the 14-3-3 protein complex and the CTLH complex, as well as the dynein light chain complex. Furthermore, we identify the protein TULP3 as a potential new member of the IFT complex A and showed that several proteins, classified as IFT complex B-associated, are integral parts of this complex. To further demonstrate EPASIS general applicability, we analyzed the modular substructure of two additional complexes, that of B-RAF and of 14-3-3-ε. The results show, that EPASIS provides a robust as well as sensitive strategy to dissect the substructure of large multiprotein complexes in a highly time- as well as cost-effective manner. PMID:24563533

  13. Pulsed laser deposition of hydroxyapatite on nanostructured titanium towards drug eluting implants.

    PubMed

    Rajesh P; Mohan, Nimmy; Yokogawa, Y; Varma, Harikrishna

    2013-07-01

    Titania nanotubes grown on titanium substrates by electrochemical anodization in glycerol-ammonium fluoride-water system were used to develop efficient drug carrying implants upon coating hydroxyapatite (HA) ceramic. The nanostructured surfaces achieved by anodization were caped with HA crystallites by pulsed laser deposition. The implant substrates were studied for their drug carrying capacity using gentamicin as a model. The nano-tubular surface with HA coating had better drug loading capacity of about 800 μg/cm(2) gentamicin while the bare anodized substrate carried less than 660 μg/cm(2). The HA coating alone stored as low as 68 μg/cm(2) and released the drug within the initial burst period itself. The ceramic coated anodized substrates were found to be more efficient in controlled delivery for longer than 160 h with a drug release of 0.5 μg/cm(2) even towards the end. The substrate with nanostructuring alone delivered the whole drug within 140 h. This study proposes the application of laser deposition of HA over nanostructured titanium, which proves to be promising towards controlled drug eluting bioceramic coated metallic prostheses.

  14. Angioscopic findings before and after thrombus-related drug-eluting stent failure.

    PubMed

    Kotani, Jun-ichi; Nanto, Shinsuke; Ueda, Yasunori; Uematsu, Masaaki; Nishino, Masami; Miyazaki, Shunichi; Yasaka, Yoshinori; Yasuda, Satoshi; Mizuno, Kyoichi

    2015-07-01

    Drug-eluting stent (DES) failure and conditions thereafter remain issues of concern despite generational advancements in DES technology. Registry data and pathological investigations have shown a variety of causes of late stent thrombosis and very late stent thrombosis. On the other hand, clinical imaging including serial studies can provide information on the conditions during the event, the previous status of the lesion, and the healing process after stent implantation. Therefore we investigated thrombus-related DES failure using coronary angioscopy (CAS), which is a robust tool for thrombus assessment. Five out of 8 thrombotic DES failures were documented during urgent repeat percutaneous coronary intervention (repeat PCI). Four patients underwent CAS before the event, and 5 patients were followed using CAS after repeat PCI for DES failure. Among these cases, there were data before and after the event in 4 patients, which highlighted various patterns of healing after repeat PCI for thrombus-related DES failure, including erosion and yellow plaque underneath the DES. The cause of thrombus formation in this series was delayed healing process, but other possible triggers included restenosis, insufficient DAPT duration, neoatherosclerosis, and vasospasm. In addition to these findings being consistent with previous segmental postmortem studies, invasive imaging modalities can provide data on more than just the event itself, such as sequential comparison and lesion features of the survivor. Accumulation of this knowledge would contribute to generating new hypothesis in the future. PMID:25666526

  15. Novel A20-gene-eluting stent inhibits carotid artery restenosis in a porcine model

    PubMed Central

    Zhou, Zhen-hua; Peng, Jing; Meng, Zhao-you; Chen, Lin; Huang, Jia-Lu; Huang, He-qing; Li, Li; Zeng, Wen; Wei, Yong; Zhu, Chu-Hong; Chen, Kang-Ning

    2016-01-01

    Background Carotid artery stenosis is a major risk factor for ischemic stroke. Although carotid angioplasty and stenting using an embolic protection device has been introduced as a less invasive carotid revascularization approach, in-stent restenosis limits its long-term efficacy and safety. The objective of this study was to test the anti-restenosis effects of local stent-mediated delivery of the A20 gene in a porcine carotid artery model. Materials and methods The pCDNA3.1EHA20 was firmly attached onto stents that had been collagen coated and treated with N-succinimidyl-3-(2-pyridyldithiol)propionate solution and anti-DNA immunoglobulin fixation. Anti-restenosis effects of modified vs control (the bare-metal stent and pCDNA3.1 void vector) stents were assessed by Western blot and scanning electron microscopy, as well as by morphological and inflammatory reaction analyses. Results Stent-delivered A20 gene was locally expressed in porcine carotids in association with significantly greater extent of re-endothelialization at day 14 and of neointimal hyperplasia inhibition at 3 months than stenting without A20 gene expression. Conclusion The A20-gene-eluting stent inhibits neointimal hyperplasia while promoting re-endothelialization and therefore constitutes a novel potential alternative to prevent restenosis while minimizing complications. PMID:27540277

  16. Acrylamide elution from roasted barley grains into mugicha and its formation during roasting.

    PubMed

    Mizukami, Yuzo; Yoshida, Mitsuru; Ono, Hiroshi

    2016-01-01

    This paper investigated acrylamide elution from roasted barley grain into mugicha and its formation during roasting of the grain. Mugicha is an infusion of roasted barley grains. Highly water-soluble acrylamide was easily extracted to mugicha from milled roasted barley grains in teabags. On the other hand, the acrylamide concentration in mugicha prepared from loose grain increased with longer simmering and steeping times. During roasting in a drum roaster, the acrylamide concentration of the grain increased as the surface temperature rose, reaching a maximum at 180-240°C. Above this temperature, the acrylamide concentration decreased with continued roasting, exhibiting an inverted 'U'-shaped curve. For most of the samples, the acrylamide concentration showed good correlation with the value of the colour space parameter L*. The dark-coloured roasted barley grains with lower L* values contained lower amounts of acrylamide as a result of deep roasting. The level of asparagine in barley grains was found to be a significant factor related to acrylamide formation in roasted barley products. The data are an important contribution to the mitigation of acrylamide intake from mugicha. PMID:26678848

  17. Pulsed laser deposition of hydroxyapatite on nanostructured titanium towards drug eluting implants.

    PubMed

    Rajesh P; Mohan, Nimmy; Yokogawa, Y; Varma, Harikrishna

    2013-07-01

    Titania nanotubes grown on titanium substrates by electrochemical anodization in glycerol-ammonium fluoride-water system were used to develop efficient drug carrying implants upon coating hydroxyapatite (HA) ceramic. The nanostructured surfaces achieved by anodization were caped with HA crystallites by pulsed laser deposition. The implant substrates were studied for their drug carrying capacity using gentamicin as a model. The nano-tubular surface with HA coating had better drug loading capacity of about 800 μg/cm(2) gentamicin while the bare anodized substrate carried less than 660 μg/cm(2). The HA coating alone stored as low as 68 μg/cm(2) and released the drug within the initial burst period itself. The ceramic coated anodized substrates were found to be more efficient in controlled delivery for longer than 160 h with a drug release of 0.5 μg/cm(2) even towards the end. The substrate with nanostructuring alone delivered the whole drug within 140 h. This study proposes the application of laser deposition of HA over nanostructured titanium, which proves to be promising towards controlled drug eluting bioceramic coated metallic prostheses. PMID:23623112

  18. Paclitaxel-eluting balloon dilation of biliary anastomotic stricture after liver transplantation

    PubMed Central

    Hüsing, Anna; Reinecke, Holger; Cicinnati, Vito R; Beckebaum, Susanne; Wilms, Christian; Schmidt, Hartmut H; Kabar, Iyad

    2015-01-01

    AIM: To investigate the safety and effectiveness of endoscopic therapy with a paclitaxel-eluting balloon (PEB) for biliary anastomotic stricture (AS) after liver transplantation (LT). METHODS: This prospective pilot study enrolled 13 consecutive eligible patients treated for symptomatic AS after LT at the University Hospital of Münster between January 2011 and March 2014. The patients were treated by endoscopic therapy with a PEB and followed up every 8 wk by endoscopic retrograde cholangiopancreatography (ERCP). In cases of re-stenosis, further balloon dilation with a PEB was performed. Follow-up was continued until 24 mo after the last intervention. RESULTS: Initial technical feasibility, defined as successful balloon dilation with a PEB during the initial ERCP procedure, was achieved in 100% of cases. Long-term clinical success (LTCS), defined as no need for further endoscopic intervention for at least 24 mo, was achieved in 12 of the 13 patients (92.3%). The mean number of endoscopic interventions required to achieve LTCS was only 1.7 ± 1.1. Treatment failure, defined as the need for definitive alternative treatment, occurred in only one patient, who developed recurrent stenosis with increasing bile duct dilatation that required stent placement. CONCLUSION: Endoscopic therapy with a PEB is very effective for the treatment of AS after LT, and seems to significantly shorten the overall duration of endoscopic treatment by reducing the number of interventions needed to achieve LTCS. PMID:25624733

  19. Effects of diffusion coefficients and struts apposition using numerical simulations for drug eluting coronary stents.

    PubMed

    Mongrain, Rosaire; Faik, Isam; Leask, Richard L; Rodés-Cabau, Josep; Larose, Eric; Bertrand, Olivier F

    2007-10-01

    In the context of drug eluting stent, we present two-dimensional numerical models of mass transport of the drug in the wall and in the lumen to study the effect of the drug diffusion coefficients in the three principal media (blood, vascular wall, and polymer coating treated as a three-compartment problem) and the impact of different strut apposition configurations (fully embedded, half embedded, and not embedded). The different conditions were analyzed in terms of their consequence on the drug concentration distribution in the arterial wall. We apply the concept of the therapeutic window to the targeted vascular wall region and derive simple metrics to assess the efficiency of the various stent configurations. Although most of the drug is dispersed in the lumen, variations in the blood flow rate within the physiological range of coronary blood flow and the diffusivity of the drug molecule in the blood were shown to have a negligible effect on the amount of drug in the wall. Our results reveal that the amount of drug cumulated in the wall depends essentially on the relative values of the diffusion coefficients in the polymer coating and in the wall. Concerning the strut apposition, it is shown that the fully embedded strut configuration would provide a better concentration distribution.

  20. PRELIMINARY REPORT ON EVALUATION OF POTENTIAL ELUANTS FOR NON-ACID ELUTION OF CESIUM FROM RESORCINOL-FORMALDEHYDE RESIN

    SciTech Connect

    Adu-Wusu, K.; Pennebaker, F.

    2010-09-01

    Small-column ion exchange (SCIX) units installed in high-level waste tanks to remove Cs-137 from highly alkaline salt solutions are among the waste treatment plans in the DOE-complex. Spherical Resorcinol-Formaldehyde (sRF) is the ion exchange resin selected for use in the Hanford Waste Treatment and Immobilization Plant (WTP). It is also the primary ion exchange material under consideration for SCIX at the Hanford site. The elution step of the multi-step ion exchange process is typically done with 0.5 M nitric acid. An acid eluant is a potential hazard in the event of a spill, leak, etc. because the high-level waste tanks are made of carbon steel. Corrosion and associated structural damage may ensue. Studies are ongoing to explore non-acid elution as an alternative. Batch contact sorption equilibrium screening tests have been conducted with 36 potential non-acid eluants. The sorption tests involve equilibrating each cesium-containing eluant solution with the sRF resin for 48 hours at 25 C in a shaker oven. In the sorption tests, an eluant is deemed to have a high cesium elution potential if it minimizes cesium sorption onto the sRF resin. The top candidates (based on lowest cesium sorption distribution coefficients) include ammonium carbonate, ammonium carbonate/ammonium hydroxide, ammonium bicarbonate, rubidium carbonate, ammonium acetate, ammonium acetate/ammonium hydroxide, ammonium bicarbonate/ammonium hydroxide, calcium chloride, and magnesium chloride. The next phase of testing for this work will focus on the following down selected eluants: Ammonium carbonate, ammonium acetate, calcium acetate, magnesium acetate, nitric acid, and ammonium hydroxide. The next testing phase is a confirmation of the elution ability of the selected eluants. It will mimic a typical sRF cesium ion exchange process i.e., sorption or loading, caustic wash, water rinse, and elution via batch contact sorption and quasi column caustic wash/water rinse/elution. Due to corrosion

  1. Isolation and characterization of Chinese standard fulvic acid sub-fractions separated from forest soil by stepwise elution with pyrophosphate buffer.

    PubMed

    Bai, Yingchen; Wu, Fengchang; Xing, Baoshan; Meng, Wei; Shi, Guolan; Ma, Yan; Giesy, John P

    2015-01-01

    XAD-8 adsorption technique coupled with stepwise elution using pyrophosphate buffers with initial pH values of 3, 5, 7, 9, and 13 was developed to isolate Chinese standard fulvic acid (FA) and then separated the FA into five sub-fractions: FApH3, FApH5, FApH7, FApH9 and FApH13, respectively. Mass percentages of FApH3-FApH13 decreased from 42% to 2.5%, and the recovery ratios ranged from 99.0% to 99.5%. Earlier eluting sub-fractions contained greater proportions of carboxylic groups with greater polarity and molecular mass, and later eluting sub-fractions had greater phenolic and aliphatic content. Protein-like components, as well as amorphous and crystalline poly(methylene)-containing components were enriched using neutral and basic buffers. Three main mechanisms likely affect stepwise elution of humic components from XAD-8 resin with pyrophosphate buffers including: 1) the carboxylic-rich sub-fractions are deprotonated at lower pH values and eluted earlier, while phenolic-rich sub-fractions are deprotonated at greater pH values and eluted later. 2) protein or protein-like components can be desorbed and eluted by use of stepwise elution as progressively greater pH values exceed their isoelectric points. 3) size exclusion affects elution of FA sub-fractions. Successful isolation of FA sub-fractions will benefit exploration of the origin, structure, evolution and the investigation of interactions with environmental contaminants. PMID:25735451

  2. Meta-analysis of randomized trials comparing the effectiveness of different strategies for the treatment of drug-eluting stent restenosis.

    PubMed

    Piccolo, Raffaele; Galasso, Gennaro; Piscione, Federico; Esposito, Giovanni; Trimarco, Bruno; Dangas, George D; Mehran, Roxana

    2014-11-01

    The investigators performed a network meta-analysis of randomized trials comparing the effectiveness of currently available strategies for the treatment of drug-eluting stent (DES) restenosis. Despite the widespread use of DES in patients who undergo percutaneous coronary intervention, the optimal treatment for DES restenosis remains poorly defined. A systematic search of electronic resources was performed. The primary end point was diameter stenosis at follow-up angiography. Seven trials were included, enrolling a total of 1,586 patients with 1,728 restenotic lesions. The following treatment options were found: balloon angioplasty (BA) in 343 patients (19.3%), iopromide-based paclitaxel-eluting balloons (PEB) in 343 (21.6%), sirolimus-eluting stents in 441 (27.8%), paclitaxel-eluting stents in 462 (29.1%), and everolimus-eluting stents in 34 (2.2%). Compared with BA, PEB (-17.74%, 95% credible interval [CI] -25.17% to -11.31%), everolimus-eluting stents (-14.93%, 95% CI -33.47% to 1.16%), paclitaxel-eluting stents (-15.3%, 95% CI -22.96% to -8.35%), and sirolimus-eluting stents (-11.08%, 95% CI -17.89% to -3.4%) had similar reductions in diameter stenosis at follow-up angiography. PEB (85%) and everolimus-eluting stents (68%) had the greatest probabilities for being the best treatment option. Furthermore, PEB were the best treatment in terms of late luminal loss (85%) and binary restenosis (85%). BA had the lowest efficacy with respect to all study end points. In conclusion, in patients with DES restenosis, repeat DES implantation and iopromide-based PEB are valid alternatives. However, PEB had greater angiographic efficacy and therefore should be considered the new benchmark comparator in the treatment of DES restenosis. The use of BA should be discouraged in patients with DES restenosis.

  3. Meta-analysis of randomized trials comparing the effectiveness of different strategies for the treatment of drug-eluting stent restenosis.

    PubMed

    Piccolo, Raffaele; Galasso, Gennaro; Piscione, Federico; Esposito, Giovanni; Trimarco, Bruno; Dangas, George D; Mehran, Roxana

    2014-11-01

    The investigators performed a network meta-analysis of randomized trials comparing the effectiveness of currently available strategies for the treatment of drug-eluting stent (DES) restenosis. Despite the widespread use of DES in patients who undergo percutaneous coronary intervention, the optimal treatment for DES restenosis remains poorly defined. A systematic search of electronic resources was performed. The primary end point was diameter stenosis at follow-up angiography. Seven trials were included, enrolling a total of 1,586 patients with 1,728 restenotic lesions. The following treatment options were found: balloon angioplasty (BA) in 343 patients (19.3%), iopromide-based paclitaxel-eluting balloons (PEB) in 343 (21.6%), sirolimus-eluting stents in 441 (27.8%), paclitaxel-eluting stents in 462 (29.1%), and everolimus-eluting stents in 34 (2.2%). Compared with BA, PEB (-17.74%, 95% credible interval [CI] -25.17% to -11.31%), everolimus-eluting stents (-14.93%, 95% CI -33.47% to 1.16%), paclitaxel-eluting stents (-15.3%, 95% CI -22.96% to -8.35%), and sirolimus-eluting stents (-11.08%, 95% CI -17.89% to -3.4%) had similar reductions in diameter stenosis at follow-up angiography. PEB (85%) and everolimus-eluting stents (68%) had the greatest probabilities for being the best treatment option. Furthermore, PEB were the best treatment in terms of late luminal loss (85%) and binary restenosis (85%). BA had the lowest efficacy with respect to all study end points. In conclusion, in patients with DES restenosis, repeat DES implantation and iopromide-based PEB are valid alternatives. However, PEB had greater angiographic efficacy and therefore should be considered the new benchmark comparator in the treatment of DES restenosis. The use of BA should be discouraged in patients with DES restenosis. PMID:25242363

  4. Isolation and characterization of Chinese standard fulvic acid sub-fractions separated from forest soil by stepwise elution with pyrophosphate buffer.

    PubMed

    Bai, Yingchen; Wu, Fengchang; Xing, Baoshan; Meng, Wei; Shi, Guolan; Ma, Yan; Giesy, John P

    2015-03-04

    XAD-8 adsorption technique coupled with stepwise elution using pyrophosphate buffers with initial pH values of 3, 5, 7, 9, and 13 was developed to isolate Chinese standard fulvic acid (FA) and then separated the FA into five sub-fractions: FApH3, FApH5, FApH7, FApH9 and FApH13, respectively. Mass percentages of FApH3-FApH13 decreased from 42% to 2.5%, and the recovery ratios ranged from 99.0% to 99.5%. Earlier eluting sub-fractions contained greater proportions of carboxylic groups with greater polarity and molecular mass, and later eluting sub-fractions had greater phenolic and aliphatic content. Protein-like components, as well as amorphous and crystalline poly(methylene)-containing components were enriched using neutral and basic buffers. Three main mechanisms likely affect stepwise elution of humic components from XAD-8 resin with pyrophosphate buffers including: 1) the carboxylic-rich sub-fractions are deprotonated at lower pH values and eluted earlier, while phenolic-rich sub-fractions are deprotonated at greater pH values and eluted later. 2) protein or protein-like components can be desorbed and eluted by use of stepwise elution as progressively greater pH values exceed their isoelectric points. 3) size exclusion affects elution of FA sub-fractions. Successful isolation of FA sub-fractions will benefit exploration of the origin, structure, evolution and the investigation of interactions with environmental contaminants.

  5. Isolation and Characterization of Chinese Standard Fulvic Acid Sub-fractions Separated from Forest Soil by Stepwise Elution with Pyrophosphate Buffer

    NASA Astrophysics Data System (ADS)

    Bai, Yingchen; Wu, Fengchang; Xing, Baoshan; Meng, Wei; Shi, Guolan; Ma, Yan; Giesy, John P.

    2015-03-01

    XAD-8 adsorption technique coupled with stepwise elution using pyrophosphate buffers with initial pH values of 3, 5, 7, 9, and 13 was developed to isolate Chinese standard fulvic acid (FA) and then separated the FA into five sub-fractions: FApH3, FApH5, FApH7, FApH9 and FApH13, respectively. Mass percentages of FApH3-FApH13 decreased from 42% to 2.5%, and the recovery ratios ranged from 99.0% to 99.5%. Earlier eluting sub-fractions contained greater proportions of carboxylic groups with greater polarity and molecular mass, and later eluting sub-fractions had greater phenolic and aliphatic content. Protein-like components, as well as amorphous and crystalline poly(methylene)-containing components were enriched using neutral and basic buffers. Three main mechanisms likely affect stepwise elution of humic components from XAD-8 resin with pyrophosphate buffers including: 1) the carboxylic-rich sub-fractions are deprotonated at lower pH values and eluted earlier, while phenolic-rich sub-fractions are deprotonated at greater pH values and eluted later. 2) protein or protein-like components can be desorbed and eluted by use of stepwise elution as progressively greater pH values exceed their isoelectric points. 3) size exclusion affects elution of FA sub-fractions. Successful isolation of FA sub-fractions will benefit exploration of the origin, structure, evolution and the investigation of interactions with environmental contaminants.

  6. Balancing Long-Term Risks of Ischemic and Bleeding Complications after Percutaneous Coronary Intervention with Drug-Eluting Stents

    PubMed Central

    Matteau, Alexis; Yeh, Robert; Camenzind, Edoardo; Steg, Ph. Gabriel; Wijns, William; Mills, Joseph; Gershlick, Anthony; de Belder, Mark; Ducrocq, Gregory; Mauri, Laura

    2015-01-01

    Introduction While trials comparing antiplatelet strategies after coronary intervention report average risks of bleeding and ischemia in a population, there is limited information to guide choices based on individual patient risks, particularly beyond one year after treatment. Methods Patient-level data from PROTECT, a broadly inclusive trial enrolling 8709 subjects treated with drug-eluting stents (sirolimus vs. zotarolimus-eluting stent), and PROTECT US, a single arm study including 1018 subjects treated with a zotarolimus-eluting stent were combined. The risk of ischemic events, cardiovascular death/non-periprocedural myocardial infarction (MI)/definite or probable stent thrombosis and the risk of bleeding events, GUSTO moderate or severe bleed were predicted using logistic regression, and the correlation between predicted ischemic and bleeding risks within individual patients was estimated. Results At median follow-up of 4.1 years, major bleeding occurred in 260 subjects (2.8%), and ischemic events in 595 (6.3%). Multivariate predictors of bleeding were: older age, smoking, diabetes mellitus, congestive heart failure, and chronic kidney disease (all p<0.05). Ischemic events shared all of the same predictors with bleeding events as well as: sex, BMI, prior MI, prior CABG, STEMI on presentation, stent length and sirolimus-eluting stent use (all p<0.05). Within individual subjects, bleeding and ischemic risks were strongly correlated (ρ=0.76, p<0.001). 97% of subjects had a greater risk of ischemic events than bleeding. Conclusions Individual patient risks of ischemia and bleeding are related to many common risk factors, yet the predicted risks of ischemic events are greater than those of major bleeding in the large majority of patients in long-term follow-up. PMID:26187674

  7. Impact on in-hospital outcomes with drug-eluting stents versus bare-metal stents (from 665,804 procedures).

    PubMed

    Badheka, Apurva O; Arora, Shilpkumar; Panaich, Sidakpal S; Patel, Nileshkumar J; Patel, Nilay; Chothani, Ankit; Mehta, Kathan; Deshmukh, Abhishek; Singh, Vikas; Savani, Ghanshyambhai T; Agnihotri, Kanishk; Grover, Peeyush; Lahewala, Sopan; Patel, Achint; Bambhroliya, Chirag; Kondur, Ashok; Brown, Michael; Elder, Mahir; Kaki, Amir; Mohammad, Tamam; Grines, Cindy; Schreiber, Theodore

    2014-12-01

    Contemporary large-scale data, regarding in-hospital outcomes depending on the types of stent used for percutaneous coronary intervention (PCI) is lacking. We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample from 2006 to 2011 using the International Classification of Diseases, Ninth Revision, Clinical Modification procedure code 36.06 (bare-metal coronary artery stent, BMS) or 36.07 (drug-eluting coronary artery stent, DES) for PCI. All analyses were performed using the designated weighting specified to the Nationwide Inpatient Sample database to minimize bias. Primary outcome was in-hospital mortality. Wald's chi-square test was used for categorical variables. We built a hierarchical 2 level model adjusted for multiple confounding factors, with hospital identification incorporated as random effects in the model and propensity match analyses were used to adjust confounding variables. A total of 665,804 procedures were analyzed, which were representative of 3,277,884 procedures in the United States. Use of bare-metal stents (BMS) was associated with greater occurrence of in-hospital mortality compared with that of drug-eluting stents (DES; 1.4% vs 0.5%, p <0.001). The association stayed significant after adjustment of various possible confounding factors (odds ratio for DES versus BMS 0.59 [0.54 to 0.64, p <0.001]) and also in propensity matched cohorts (1.2% vs 0.7%, p <0.001). The results continued to be similar in the following high-risk subgroups: diabetes (0.57 [0.50 to 0.64, <0.001]), acute myocardial infarction and/or shock (0.53 [0.49 to 0.57, <0.001]), age >80 (0.66 [0.58 to 0.74, <0.001]), and multivessel PCI (0.55 [0.46 to 0.66, <0.001]). In conclusion, DES use was associated with lesser in-hospital mortality compared with BMS. This outcome benefit was seen across subgroups in various subgroups including elderly, diabetics, and acute myocardial infarction as well as multivessel interventions. PMID:25439448

  8. Transarterial embolisation of hepatocellular carcinoma with doxorubicin-eluting beads: single centre early experience

    PubMed Central

    Nawawi, O; Hazman, MN; Abdullah, BJJ; Vijayananthan, A; Manikam, J; Mahadeva, S; Goh, KL

    2010-01-01

    Purpose: This is a retrospective study to evaluate the results of our early experience of using doxorubicin eluting beads (DEB) to treat patients with early and intermediate hepatocellular carcinoma (HCC). Material and methods: A cohort of 19 patients (84.2% male; 15.8% female; mean age 59.2 years ± 11.0; range, 32-80 years) with documented HCC of size 1.8-10cm (mean, 4.0cm ± 1.8 ) undergoing DEB transarterial chembolisation (TACE) was reviewed. All patients had at least one image examination (multiphase computed tomography or magnetic resonance imaging) after embolisation. Results: A total of 32 procedures were performed. The objective response according to the European Association for the Study of the Liver criteria was 57.9% at 1-month, 42.8% at 6-month and 50.0% at 1-year follow up. There were 4 (21.1%) treatment-related complications (1 liver abscess, 2 pancreatitis and 1 tumour rupture) which resulted in 2 deaths. One death occurred 3 weeks after second embolisation, due to ruptured pancreatic pseudocyst, giving a 5.3% 30-day mortality rate. Another patient died 2 months after embolisation caused by tumour rupture. Eight patients received radiofrequency ablation after embolisation for residual or recurrent tumours. The 1-year survival rate in the DEB TACE only group was 80% while the 1- and 2-year survival rate in the group that received radiofrequency after DEB TACE was 85.7% and 100% respectively. Conclusion: DEB TACE is safe and effective in select group of patients. Survival may be improved when combined with other treatment modality. PMID:21611067

  9. Biocompatible polymer coating of titania nanotube arrays for improved drug elution and osteoblast adhesion.

    PubMed

    Gulati, Karan; Ramakrishnan, Saminathan; Aw, Moom Sinn; Atkins, Gerald J; Findlay, David M; Losic, Dusan

    2012-01-01

    Bacterial infection, extensive inflammation and poor osseointegration have been identified as the major reasons for [early] orthopaedic implant failures based on titanium. Creating implants with drug-eluting properties to locally deliver drugs is an appealing way to address some of these problems. To improve properties of titanium for orthopaedic applications, this study explored the modification of titanium surfaces with titaniananotube (TNT) arrays, and approach that combines drug delivery into bone and potentially improved bone integration. A titania layer with an array of nanotube structures (∼120 nm in diameter and 50 μm in length) was synthesized on titanium surfaces by electrochemical anodization and loaded with the water-insoluble anti-inflammatory drug indomethacin. A simple dip-coating process of polymer modification formed thin biocompatible polymer films over the drug-loaded TNTs to create TNTs with predictable drug release characteristics. Two biodegradable and antibacterial polymers, chitosan and poly(lactic-co-glycolic acid), were tested for their ability to extend the drug release time of TNTs and produce favourable bone cell adhesion properties. Dependent on polymer thickness, a significant improvement in the drug release characteristics was demonstrated, with reduced burst release (from 77% to >20%) and extended overall release from 4 days to more than 30 days. Excellent osteoblast adhesion and cell proliferation on polymer-coated TNTs compared with uncoated TNTs were also observed. These results suggest that polymer-modified implants with a TNT layer are capable of delivering a drug to a bone site over an extended period and with predictable kinetics. In addition, favourable bone cell adhesion suggests that such an implant would have good biocompatibility. The described approach is broadly applicable to a wide range of drugs and implants currently used in orthopaedic practice. PMID:21930254

  10. Risk of drug-eluting stent thrombosis in patients receiving proton pump inhibitors.

    PubMed

    Sarafoff, Nikolaus; Sibbing, Dirk; Sonntag, Ulrich; Ellert, Julia; Schulz, Stefanie; Byrne, Robert A; Mehilli, Julinda; Schömig, Albert; Kastrati, Adnan

    2010-09-01

    Clopidogrel is a prodrug that is converted via the hepatic cytochrome P450 system into its active thiol metabolite. Evidence is accumulating that proton pump inhibitors (PPIs) inhibit this enzymatic pathway and may therefore attenuate the antiplatelet effect of clopidogrel. The objective of this study was to investigate whether patients on clopidogrel therapy after drug-eluting stent (DES) placement who also receive a PPI are at higher risk of stent thrombosis (ST). This is a retrospective analysis of patients who received dual antiplatelet treatment including clopidogrel after DES placement. Outcomes were compared according to PPI therapy. The primary endpoint was the incidence of definite ST at 30 days. Secondary endpoints were death, combined death or ST and myocardial infarction (MI). The study population included 3,338 patients and 698 patients (20.9%) received PPIs. Patients receiving a PPI had a higher risk profile at baseline. Multivariate analysis showed that PPI treatment was not independently associated with the occurrence of ST [adjusted HR 1.8 (95% CI: 0.7-4.7), p=0.23] or MI [adjusted HR 1.3 (0.8-2.3), p=0.11]. PPI treatment was significantly associated with death [adjusted HR 2.2 (1.1-4.3), p=0.02] and death or ST [adjusted HR 3.3(1.7-6.7), p=0.02]. Concomitant treatment with a PPI in patients receiving dual antiplatelet treatment after coronary stenting is not an independent predictor of ST. The higher mortality is probably due to confounding as patients on PPIs had a higher risk profile at baseline. PMID:20664905

  11. A Budget Impact Model for Paclitaxel-eluting Stent in Femoropopliteal Disease in France

    SciTech Connect

    De Cock, Erwin; Sapoval, Marc; Julia, Pierre; Lissovoy, Greg de; Lopes, Sandra

    2013-04-15

    The Zilver PTX drug-eluting stent (Cook Ireland Ltd., Limerick, Ireland) represents an advance in endovascular treatments for atherosclerotic superficial femoral artery (SFA) disease. Clinical data demonstrate improved clinical outcomes compared to bare-metal stents (BMS). This analysis assessed the likely impact on the French public health care budget of introducing reimbursement for the Zilver PTX stent. A model was developed in Microsoft Excel to estimate the impact of a progressive transition from BMS to Zilver PTX over a 5-year horizon. The number of patients undergoing SFA stenting was estimated on the basis of hospital episode data. The analysis from the payer perspective used French reimbursement tariffs. Target lesion revascularization (TLR) after primary stent placement was the primary outcome. TLR rates were based on 2-year data from the Zilver PTX single-arm study (6 and 9 %) and BMS rates reported in the literature (average 16 and 22 %) and extrapolated to 5 years. Net budget impact was expressed as the difference in total costs (primary stenting and reinterventions) for a scenario where BMS is progressively replaced by Zilver PTX compared to a scenario of BMS only. The model estimated a net cumulative 5-year budget reduction of Euro-Sign 6,807,202 for a projected population of 82,316 patients (21,361 receiving Zilver PTX). Base case results were confirmed in sensitivity analyses. Adoption of Zilver PTX could lead to important savings for the French public health care payer. Despite higher initial reimbursement for the Zilver PTX stent, fewer expected SFA reinterventions after the primary stenting procedure result in net savings.

  12. Comparison of Full Lesion Coverage versus Spot Drug-Eluting Stent Implantation for Coronary Artery Stenoses

    PubMed Central

    Kim, Seunghwan; Yun, Kyeong Ho; Shin, Dong-Ho; Kim, Jung-Sun; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo

    2014-01-01

    Purpose The aim of this study was to evaluate and compare the long-term clinical outcomes of the spot drug-eluting stent (DES) implantation strategy, which is used to minimize implanted stent length and the number of stents, versus full lesion coverage for treatment of coronary artery stenoses. Materials and Methods We evaluated 1-year clinical outcomes of 1619 patients with stent implantation for a single coronary lesion. They were divided into two groups: those treated by full lesion coverage (n=1200) and those treated with the spot stenting strategy (n=419). The combined occurrence of 1-year target vessel failure (TVF), including cardiac death, target-vessel related myocardial infarction, or ischemia-driven target-vessel revascularization was evaluated. Results The spot DES implantation group had a shorter stent length (23.14±9.70 mm vs. 25.44±13.24 mm, respectively; p<0.001) and a fewer number of stents (1.09±0.30 vs. 1.16±0.41, respectively; p<0.001), even though the average lesion length was similar to the full lesion coverage group (21.36±10.30 mm vs. 20.58±10.97 mm, respectively; p=0.206). Spot DES implantation was superior to full DES coverage with respect to 1-year TVF (1.4% vs. 3.3%, p=0.044). Cox proportional hazard model analysis showed that the risk for 1-year TVF was almost 60% lower among patients who received spot DESs compared to those who received full DES coverage after adjustment for other risk factors (HR=0.40, 95% confidence interval=0.17-0.98; p=0.046). Conclusion Minimizing stent length and the number of stents with overlapping by spot DES implantation may result in reduced rates of 1-year TVF, compared with full DES coverage. PMID:24719123

  13. Drug diffusion and biological responses of arteries using a drug-eluting stent with nonuniform coating

    PubMed Central

    Saito, Noboru; Mori, Yuhei; Uchiyama, Sayaka

    2016-01-01

    The purpose of this study was to determine the effect of a nonuniform coating, abluminal-gradient coating (AGC), which leaves the abluminal surface of the curves and links parts of the stent free from the drug coating, on the diffusion direction of the drug and the biological responses of the artery to drug-eluting stent (DES) by comparing the AGC-sirolimus stent and the conventional full-surface coating (CFC) sirolimus stent. The study aimed to verify whether the AGC approach was appropriate for the development of a safer DES, minimizing the risks of stent thrombosis due to delayed endothelialization by the drug and distal embolization due to cracking of the coating layer on the hinge parts of the DES on stent expansion. In the in vitro local drug diffusion study, we used rhodamine B as a model drug, and rhodamine B released from the AGC stent diffused predominantly into the abluminal side of the alginate artery model. Conversely, rhodamine B released from the CFC stent quickly spread to the luminal side of the artery model, where endothelial cell regeneration is required. In the biological responses study, the luminal surface of the iliac artery implanted with the AGC-sirolimus stent in a rabbit iliac artery for 2 weeks was completely covered with endothelial-like cells. On the other hand, the luminal surface of the iliac artery implanted with the CFC-sirolimus stent for 2 weeks only showed partial coverage with endothelial-like cells. While thrombosis was observed in two of the three CFC-sirolimus stents, it was observed in only one of the three AGC-sirolimus stents. Taken together, these findings indicate that the designed nonuniform coating (AGC) is an appropriate approach to ensure a safer DES. However, the number of studies is limited and a larger study should be conducted to reach a statistically significant conclusion. PMID:27051322

  14. Durable Clinical Effectiveness With Paclitaxel-Eluting Stents in the Femoropopliteal Artery

    PubMed Central

    Ansel, Gary M.; Jaff, Michael R.; Ohki, Takao; Saxon, Richard R.; Smouse, H. Bob; Machan, Lindsay S.; Snyder, Scott A.; O’Leary, Erin E.; Ragheb, Anthony O.; Zeller, Thomas

    2016-01-01

    Background— This randomized controlled trial evaluated clinical durability of Zilver PTX, a paclitaxel-coated drug-eluting stent (DES), for femoropopliteal artery lesions. Outcomes compare primary DES versus percutaneous transluminal angioplasty (PTA), overall DES (primary and provisional) versus standard care (PTA and provisional Zilver bare metal stent [BMS]), and provisional DES versus provisional BMS. Methods and Results— Patients with symptomatic femoropopliteal artery disease were randomly assigned to DES (n=236) or PTA (n=238). Approximately 91% had claudication; 9% had critical limb ischemia. Patients experiencing acute PTA failure underwent secondary randomization to provisional BMS (n=59) or DES (n=61). The 1-year primary end points of event-free survival and patency showed superiority of primary DES in comparison with PTA; these results were sustained through 5 years. Clinical benefit (freedom from persistent or worsening symptoms of ischemia; 79.8% versus 59.3%, P<0.01), patency (66.4% versus 43.4%, P<0.01), and freedom from reintervention (target lesion revascularization, 83.1% versus 67.6%, P<0.01) for the overall DES group were superior to standard care in nonrandomized comparisons. Similarly, clinical benefit (81.8% versus 63.8%, P=0.02), patency (72.4% versus 53.0%, P=0.03), and freedom from target lesion revascularization (84.9% versus 71.6%, P=0.06) with provisional DES were improved over provisional BMS. These results represent >40% relative risk reduction for restenosis and target lesion revascularization through 5 years for the overall DES in comparison with standard care and for provisional DES in comparison with provisional BMS. Conclusions— The 5-year results from this large study provide long-term information previously unavailable regarding endovascular treatment of femoropopliteal artery disease. The Zilver PTX DES provided sustained safety and clinical durability in comparison with standard endovascular treatments. Clinical Trial

  15. Elution-extrusion counter-current chromatography for the separation of two pairs of isomeric monoterpenes from Paeoniae Alba Radix.

    PubMed

    Chu, Chu; Zhang, Shidi; Tong, Shengqiang; Li, Xingnuo; Li, Qingyong; Yan, Jizhong

    2015-09-01

    In this work, a simple and efficient protocol for the rapid separation of two pairs of isomeric monoterpenes from Paeoniae Alba Radix was developed by combining macroporous resin and elution-extrusion counter-current chromatography. The crude extract was firstly subjected to a D101 macroporous resin column eluted with water and a series of different concentrations of ethanol. Then, effluents of 30 and 95% ethanol were collected as sample 1 and sample 2 for further counter-current chromatography purification. Finally, a pair of isomers, 96 mg of compound 1 and 48 mg of compound 2 with purities of 91.1 and 96.2%, respectively, was isolated from 200 mg of sample 1. The other pair of isomers, 14 mg of compound 3 and 8 mg of compound 4 with purities of 93.6 and 88.9%, respectively, was isolated from 48 mg of sample 2. Their purities were analyzed by high-performance liquid chromatography, and their chemical structures were identified by mass spectrometry and (1) H NMR spectroscopy. Compared to a normal counter-current chromatography separation, the separation time and solvent consumption of elution-extrusion counter-current chromatography were reduced while the resolutions were still good. The established protocol is promising for the separation of natural products with great disparity of content in herbal medicines.

  16. Complete elution of vacuum gas oil resins by comprehensive high-temperature two-dimensional gas chromatography.

    PubMed

    Boursier, Laure; Souchon, Vincent; Dartiguelongue, Cyril; Ponthus, Jérémie; Courtiade, Marion; Thiébaut, Didier

    2013-03-01

    The development of efficient conversion processes requires extended knowledge on vacuum gas oils (VGOs). Among these processes, hydrocracking is certainly one of the best suited to meet the increasing demand on high quality diesel fuels. Most of refractory and inhibiting compounds towards hydrocracking and especially nitrogen containing compounds are contained in a fraction of the VGO called the resin fraction, which corresponds to the most polar fraction of a VGO obtained by liquid chromatography (LC) fractionation on a silica column. However, the lack of resolution observed through existing analytical methods does not allow a detailed characterization of these fractions. A recent study showed that comprehensive high temperature two-dimensional gas chromatography (HT-GC×GC) methods could be optimized in order to elute heavy compounds. This method was implemented for the analysis of VGO resin fractions and complete elution was reached. Firstly, the method was validated through repeatability, accuracy, linearity and response factors calculations. Four VGO resin fractions were analyzed and their HT-GC×GC simulated distillation curves were compared to their GC simulated distillation (GC-SimDist) curves. This comparison showed that the method allows complete elution of most of the analyzed VGO resin fractions. However, a detailed characterization of these fractions is not yet obtained due to the very large number of heteroatomic and aromatic species that a flame ionization detector can detect. Current work aims at increasing the selectivity of GC×GC by using heteroatom selective detectors in order to improve the characterization of such products. PMID:23375830

  17. Elution of uranium and transition metals from amidoxime-based polymer adsorbents for sequestering uranium from seawater

    DOE PAGES

    Pan, Horng-Bin; Kuo, Li-Jung; Miyamoto, Naomi; Wood, Jordana; Strivens, Jonathan E.; Gill, Gary; Janke, Christopher James; Wai, Chien

    2015-11-30

    High-surface-area amidoxime and carboxylic acid grafted polymer adsorbents developed at Oak Ridge National Laboratory were tested for sequestering uranium in a flowing seawater flume system at the PNNL-Marine Sciences Laboratory. FTIR spectra indicate that a KOH conditioning process is necessary to remove the proton from the carboxylic acid and make the sorbent effective for sequestering uranium from seawater. The alkaline conditioning process also converts the amidoxime groups to carboxylate groups in the adsorbent. Both Na2CO3 H2O2 and hydrochloric acid elution methods can remove ~95% of the uranium sequestered by the adsorbent after 42 days of exposure in real seawater. Themore » Na2CO3 H2O2 elution method is more selective for uranium than conventional acid elution. Iron and vanadium are the two major transition metals competing with uranium for adsorption to the amidoxime-based adsorbents in real seawater. Tiron (4,5-Dihydroxy-1,3-benzenedisulfonic acid disodium salt, 1 M) can remove iron from the adsorbent very effectively at pH around 7. The coordination between vanadium (V) and amidoxime is also discussed based on our 51V NMR data.« less

  18. Elution of uranium and transition metals from amidoxime-based polymer adsorbents for sequestering uranium from seawater

    SciTech Connect

    Pan, Horng-Bin; Kuo, Li-Jung; Miyamoto, Naomi; Wood, Jordana; Strivens, Jonathan E.; Gill, Gary; Janke, Christopher James; Wai, Chien

    2015-11-30

    High-surface-area amidoxime and carboxylic acid grafted polymer adsorbents developed at Oak Ridge National Laboratory were tested for sequestering uranium in a flowing seawater flume system at the PNNL-Marine Sciences Laboratory. FTIR spectra indicate that a KOH conditioning process is necessary to remove the proton from the carboxylic acid and make the sorbent effective for sequestering uranium from seawater. The alkaline conditioning process also converts the amidoxime groups to carboxylate groups in the adsorbent. Both Na2CO3 H2O2 and hydrochloric acid elution methods can remove ~95% of the uranium sequestered by the adsorbent after 42 days of exposure in real seawater. The Na2CO3 H2O2 elution method is more selective for uranium than conventional acid elution. Iron and vanadium are the two major transition metals competing with uranium for adsorption to the amidoxime-based adsorbents in real seawater. Tiron (4,5-Dihydroxy-1,3-benzenedisulfonic acid disodium salt, 1 M) can remove iron from the adsorbent very effectively at pH around 7. The coordination between vanadium (V) and amidoxime is also discussed based on our 51V NMR data.

  19. Elution of Uranium and Transition Metals from Amidoxime-Based Polymer Adsorbents for Sequestering Uranium from Seawater

    SciTech Connect

    Pan, Horng-Bin; Kuo, Li-Jung; Wai, Chien M.; Miyamoto, Naomi; Joshi, Ruma; Wood, Jordana R.; Strivens, Jonathan E.; Janke, Christopher J.; Oyola, Yatsandra; Das, Sadananda; Mayes, Richard T.; Gill, Gary A.

    2015-11-30

    High-surface-area amidoxime and carboxylic acid grafted polymer adsorbents developed at Oak Ridge National Laboratory were tested for sequestering uranium in a flowing seawater flume system at the PNNL-Marine Sciences Laboratory. FTIR spectra indicate that a KOH conditioning process is necessary to remove the proton from the carboxylic acid and make the sorbent effective for sequestering uranium from seawater. The alkaline conditioning process also converts the amidoxime groups to carboxylate groups in the adsorbent. Both Na2CO3-H2O2 and hydrochloric acid elution methods can remove ~95% of the uranium sequestered by the adsorbent after 42 days of exposure in real seawater. The Na2CO3-H2O2 elution method is more selective for uranium than conventional acid elution. Iron and vanadium are the two major transition metals competing with uranium for adsorption to the amidoxime-based adsorbents in real seawater.

  20. The effect of an alendronate-eluting titanium system to induce osteogenic differentiation in human buccal fat cells (HBFCs)

    NASA Astrophysics Data System (ADS)

    Kim, Sung Eun; Lee, Su-Young; Yun, Young-Pil; Lee, Jae Yong; Park, Kyeongsoon; Lee, Deok-Won; Song, Hae-Ryong

    2012-10-01

    The purpose of this study was to develop alendronate (Aln)-eluting Ti substrates to induce osteogenic differentiation of human buccal fat cells (HBFCs). The surface of pristine Ti was modified by dopamine (DOPA) and then heparin was grafted onto the aminated Ti surfaces to achieve the Aln-eluting Ti system. Aln was subsequently immobilized on the surface of heparinized Ti (Hep-Ti). Pristine Ti and surface-modified-Ti were characterized by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and contact angle. Osteogenic differentiation of HBFCs on the surface of pristine-Ti, Hep-Ti, Aln (1 mg)/Hep-Ti, and Aln (5 mg)/Hep-Ti was demonstrated by alkaline phosphatase (ALP) activity, calcium deposition, and osteocalcin and osteopontin mRNA expression. Successful immobilization of Aln on Hep-Ti was confirmed by XPS and contact angle. Aln/Hep-Ti showed the sustained release for up to 28 days. Additionally, HBFCs cultured on Aln/Hep-Ti substrates showed significantly induced ALP activity, calcium deposition, and osteocalcin and osteopontin mRNA expression. These results suggest that Aln-eluting Ti substrates have a potential effect on osteogenic differentiation of HBFCs and will be a promising material for bone regeneration.

  1. Sirolimus-loaded CaP coating on Co-Cr alloy for drug-eluting stent

    PubMed Central

    Yang, Jingxin; Lee, In-Seop; Cui, Fuzhai

    2016-01-01

    To achieve polymer-free and controllable drug-eluting system, there have been many efforts to modify the surface composition and topography of metal stent. Recently, calcium phosphate is commonly applied to metallic implants as a coating material for fast fixation and firm-implant bone attachment on the account of its demonstrated bioactive and osteoconductive properties. In the present study, the release of sirolimus could be controllable because of immobilization of sirolimus during the process of biomimetic CaP coating forming. A completely new concept is the drug carrier of biomimetic CaP coating with sirolimus for an absorbable drug eluting system, which in turn can serve as a drug reservoir. We here describe the characteristic, mechanisms and drug release in vitro of new drug-eluting system in comparison to conventional system equivalent. Nano-structured calcium phosphate (CaP) coating was formed on the cobalt–chromium (Co-Cr) alloy substrate. By immersing coated sample in solution with sirolimus (rapamycin), the sirolimus could be immobilized in the newly formed CaP layer. The morphology, composition and formation process of the coating were studied with scanning electron microscopy, energy dispersive spectrometer, X-ray diffraction and X-ray photoelectron spectroscopy. The results showed that a uniform CaP coating incorporated with sirolimus was observed on Co-Cr alloy. PMID:27252886

  2. Simultaneous determinations by theophylline and its major metabolites in urine by reversed-phase ion-pair high-performance liquid chromatography.

    PubMed

    Muir, K T; Jonkman, J H; Tang, D S; Kunitani, M; Riegelman, S

    1980-11-14

    A new, highly slective high-performance liquid-chromatographic (HPLC) assay for theophylline and its major metabolites in urine is described. The method utilizes an ion-pair extraction followed by separation and quantitation by reversed-phase ion-pair gradient-elution HPLC. Comparison with several other methods showed that interferences were present in too many blank urine samples to allow for the accurate quantitation of the metabolites of theophylline by direct injection--isocratic HPLC assays. Sample processing involving ion-pair complexing and extraction together with gradient-elution systems is recommended for accurate pharmacokinetic studies.

  3. Evaluation of the celite secondary concentration procedure and an alternate elution buffer for the recovery of enteric adenoviruses 40 and 41

    EPA Science Inventory

    The effective recovery of adenovirus from water is a critical first step in developing a virus occurrence method able to provide accurate data for risk assessments and other applications. During virus concentration, electropositive filters are typically eluted with beef extract,...

  4. Systematic Review of Infrapopliteal Drug-Eluting Stents: A Meta-Analysis of Randomized Controlled Trials

    SciTech Connect

    Katsanos, Konstantinos; Spiliopoulos, Stavros; Diamantopoulos, Athanasios; Karnabatidis, Dimitris; Sabharwal, Tarun; Siablis, Dimitris

    2013-06-15

    IntroductionDrug-eluting stents (DES) have been proposed for the treatment of infrapopliteal arterial disease. We performed a systematic review to provide a qualitative analysis and quantitative data synthesis of randomized controlled trials (RCTs) assessing infrapopliteal DES.Materials and MethodsPubMed (Medline), EMBASE (Excerpta Medical Database), AMED (Allied and Complementary medicine Database), Scopus, CENTRAL (Cochrane Central Register of Controlled Trials), online content, and abstract meetings were searched in September 2012 for eligible RCTs according to the preferred reporting items for systematic reviews and meta-analyses selection process. Risk of bias was assessed using the Cochrane Collaboration's tool. Primary endpoint was primary patency defined as absence of {>=}50 % vessel restenosis at 1 year. Secondary outcome measures included patient survival, limb amputations, change of Rutherford-Becker class, target lesion revascularization (TLR) events, complete wound healing, and event-free survival at 1 year. Risk ratio (RRs) were calculated using the Mantel-Haenszel fixed effects model, and number-needed-to-treat values are reported.ResultsThree RCTs involving 501 patients with focal infrapopliteal lesions were analyzed (YUKON-BTX, DESTINY, and ACHILLES trials). All three RCTs included relatively short and focal infrapopliteal lesions. At 1 year, there was clear superiority of infrapopliteal DES compared with control treatments in terms of significantly higher primary patency (80.0 vs. 58.5 %; pooled RR = 1.37, 95 % confidence interval [CI] = 1.18-1.58, p < 0.0001; number-needed-to-treat (NNT) value = 4.8), improvement of Rutherford-Becker class (79.0 vs. 69.6 %; pooled RR = 1.13, 95 % CI = 1.002-1.275, p = 0.045; NNT = 11.1), decreased TLR events (9.9 vs. 22.0 %; pooled RR = 0.45, 95 % CI = 0.28-0.73, p = 0.001; NNT = 8.3), improved wound healing (76.8 vs. 59.7 %; pooled RR = 1.29, 95 % CI = 1.02-1.62, p = 0.04; NNT = 5.9), and better overall event

  5. Development of an Experimental Drug Eluting Suprachoroidal Microstent as Glaucoma Drainage Device

    PubMed Central

    Hovakimyan, Marina; Siewert, Stefan; Schmidt, Wolfram; Sternberg, Katrin; Reske, Thomas; Stachs, Oliver; Guthoff, Rudolf; Wree, Andreas; Witt, Martin; Schmitz, Klaus-Peter; Allemann, Reto

    2015-01-01

    Purpose: A novel glaucoma drainage device (GDD) with local drug delivery (LDD) system was created and characterized for safety and effectiveness after implantation into the suprachoroidal space (SCS) of rabbit eyes. Methods: Thin films of two different polymers, Poly(3-hydroxybutyrate) (P(3HB)) and Poly(4-hydroxybutyrate) (P(4HB)), containing the drugs mitomycin C (MitC) or paclitaxel (PTX) were attached to silicone-tubes to create LDD devices. The release kinetics of these drugs were explored in vitro using high performance liquid chromatography (HPLC).  Twenty-four New Zealand white rabbits, randomly divided into eight groups, were implanted with different kinds of microstents into SCS. The intraocular pressure (IOP) was monitored noninvasively. After 6 weeks, rabbits were sacrificed and enucleated eyes were used for anterior segment optical coherence tomography (OCT), micro magnetic resonance imaging (MRI), and histology. Results: In vitro, faster drug release from both polymers was observed for MitC compared to PTX. Comparing polymers, the release from P(3HB) matrix was slower for both drugs. MRI and OCT showed all implants maintained a proper location. An effective IOP reduction was observed for up to 6 weeks in eyes with microstents combined with a drug-releasing LDD system. Overall, the surrounding tissue revealed mild-to-moderate inflammation. No pronounced fibrosis was observed in any of the groups. However, both drugs caused damage to the neighboring retina. Conclusions: The suprachoroidal microstent reduced IOP with mild inflammation in rabbit eyes. To avoid negative effects on the retina, it is necessary to identify novel drugs with less cytotoxicity. Future studies are needed to explore the fibrotic process over the long-term. Translational Relevance: The presented data serve as a proof of principle study for the concept of a suprachoroidal drug eluting microstent. Future device improvements will be focused on the design of LDD systems and the use of

  6. Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model

    SciTech Connect

    Rao, Pramod P.; Pascale, Florentina; Seck, Atman; Auperin, Anne; Drouard-Troalen, Laurence; Deschamps, Frederic; Teriitheau, Christophe; Paci, Angelo; Denys, Alban; Bize, Pierre; Baere, Thierry de

    2012-12-15

    Purpose: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. Material and Methods: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.ResultsTwelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). Conclusion: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

  7. Kinetic performance limits of constant pressure versus constant flow rate gradient elution separations. Part I: theory.

    PubMed

    Broeckhoven, K; Verstraeten, M; Choikhet, K; Dittmann, M; Witt, K; Desmet, G

    2011-02-25

    We report on a general theoretical assessment of the potential kinetic advantages of running LC gradient elution separations in the constant-pressure mode instead of in the customarily used constant-flow rate mode. Analytical calculations as well as numerical simulation results are presented. It is shown that, provided both modes are run with the same volume-based gradient program, the constant-pressure mode can potentially offer an identical separation selectivity (except from some small differences induced by the difference in pressure and viscous heating trajectory), but in a significantly shorter time. For a gradient running between 5 and 95% of organic modifier, the decrease in analysis time can be expected to be of the order of some 20% for both water-methanol and water-acetonitrile gradients, and only weakly depending on the value of V(G)/V₀ (or equivalently t(G)/t₀). Obviously, the gain will be smaller when the start and end composition lie closer to the viscosity maximum of the considered water-organic modifier system. The assumptions underlying the obtained results (no effects of pressure and temperature on the viscosity or retention coefficient) are critically reviewed, and can be inferred to only have a small effect on the general conclusions. It is also shown that, under the adopted assumptions, the kinetic plot theory also holds for operations where the flow rate varies with the time, as is the case for constant-pressure operation. Comparing both operation modes in a kinetic plot representing the maximal peak capacity versus time, it is theoretically predicted here that both modes can be expected to perform equally well in the fully C-term dominated regime (where H varies linearly with the flow rate), while the constant pressure mode is advantageous for all lower flow rates. Near the optimal flow rate, and for linear gradients running from 5 to 95% organic modifier, time gains of the order of some 20% can be expected (or 25-30% when accounting for

  8. Neointimal hyperplasia persists at six months after sirolimus-eluting stent implantation in diabetic porcine

    PubMed Central

    Zhang, Qi; Lu, Lin; Pu, LiJin; Zhang, RuiYan; Shen, Jie; Zhu, ZhengBing; Hu, Jian; Yang, ZhenKun; Chen, QiuJin; Shen, WeiFeng

    2007-01-01

    Background Observational clinical studies have shown that patients with diabetes have less favorable results after percutaneous coronary intervention compared with the non-diabetic counterparts, but its mechanism remains unclear. The aim of this study was to examine the changes of neointimal hyperplasia after sirolimus-eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the impact of aortic inflammation on this proliferative process. Methods Diabetic porcine model was created with an intravenous administration of a single dose of streptozotocin in 15 Chinese Guizhou minipigs (diabetic group); each of them received 2 SES (Firebird, Microport Co, China) implanted into 2 separated major epicardial coronary arteries. Fifteen non-diabetic minipigs with SES implantation served as controls (control group). At 6 months, the degree of neointimal hyperplasia was determined by repeat coronary angiography, intravascular ultrasound (IVUS) and histological examination. Tumor necrosis factor (TNF)-α protein level in the aortic intima was evaluated by Western blotting, and TNF-α, interleukin (IL)-1β and IL-6 mRNA levels were assayed by reverse transcription and polymerase chain reaction. Results The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were comparable between the two groups. At 6-month follow-up, the degree of in-stent restenosis (40.4 ± 24.0% vs. 20.2 ± 17.7%, p < 0.05), late lumen loss (0.33 ± 0.19 mm vs. 0.10 ± 0.09 mm, p < 0.001) by quantitative angiography, percentage of intimal hyperplasia in the stented area (26.7 ± 19.2% vs. 7.3 ± 6.1%, p < 0.001) by IVUS, and neointimal area (1.59 ± 0.76 mm2 vs. 0.41 ± 0.18 mm2, p < 0.05) by histological examination were significantly exacerbated in the diabetic group than those in the controls. Significant increases in TNF-α protein and TNF-α, IL-1β and IL-6 mRNA levels were observed in aortic intima in the diabetic group

  9. Sorption of uranium from carbonate solutions by thin-layer sorbents based on titanium hydroxoperoxide and activated carbon, and the elution of uranium

    SciTech Connect

    Prishchepo, R.S.; Betenekov, N.D.; Pershko, A.A.; Vasilevskii, V.A.

    1986-05-01

    This paper studies the sorption of uranium from carbonate solutions and the elution of uranium under static conditions, on thin-layer inorganic sorbents obtained by homogeneous precipitation of titanium hydroperoxide on SKT activated carbon. The exchange capacity of the sorbents for uranium has been determined in relation to the quantity of titanium in the film, the sorbent particle size, and the contact time. Conditions have been selected for the elution.

  10. Toxicity of Irinotecan-Eluting Beads in the Treatment of Hepatic Malignancies: Results of a Multi-Institutional Registry

    SciTech Connect

    Martin, R. C. G.; Howard, J.; Tomalty, D.; Robbins, K.; Padr, R.; Bosnjakovic, P. M.; Tatum, Cliff

    2010-10-15

    PurposeTo evaluate the predictors of toxicity of drug-eluting beads loaded with irinotecan (DEBIRI) in the treatment of hepatic malignancies.Materials and MethodsA total of 330 patients were enrolled in a prospective, open-label, multicenter, multinational, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). Complications were graded by Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included.ResultsA total of 109 patients received 187 DEBIRI treatments (range 1 to 5 per patient). The most common histology was metastatic colorectal cancer in 76% of patients, cholangiocarcinoma in 7% of patients, and other metastatic disease in 17% of patients. There were 35 patients (19%) with irinotecan treatments who sustained 158 treatment-related adverse events, with the median CTCAE event grade being CTCAE grade 2 (range 1 to 5). The most common adverse events were postembolic symptoms (42%). Multivariate analysis identified pretreatment and treatment-related risk factors as follows: lack of pretreatment with hepatic arterial lidocaine (p = 0.005), {>=}3 treatments (p = 0.05), achievement of complete stasis (p = 0.04), treatment with >100 mg DEBIRI in 1 treatment (p = 0.03), and bilirubin >2.0 {mu}g/dl with >50% liver involvement (p = 0.05). These factors were predictive of adverse events and significantly greater hospital length of stay.ConclusionsDEBIRI is safe when appropriate technique and treatment are used. Adverse events can be predicted based on pretreatment- and treatment-related factors, and their occurrence can become part of the informed consent process. Continued standardization of this treatment will lead to fewer adverse events and improved patient quality of life.

  11. Long-term Outcomes of Drug-eluting versus Bare-metal stent for ST-elevation Myocardial Infarction

    PubMed Central

    Wang, Liping; Wang, Hongyun; Dong, Pingshuan; Li, Zhuanzhen; Wang, Yanyu; Duan, Nana; Zhao, Yuwei; Wang, Shaoxin

    2014-01-01

    Background Long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain uncertain. Objective To investigate long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI). Methods We performed search of MEDLINE, EMBASE, the Cochrane library, and ISI Web of Science (until February 2013) for randomized trials comparing more than 12-month efficacy or safety of DES with BMS in patients with STEMI. Pooled estimate was presented with risk ratio (RR) and its 95% confidence interval (CI) using random-effects model. Results Ten trials with 7,592 participants with STEMI were included. The overall results showed that there was no significant difference in the incidence of all-cause death and definite/probable stent thrombosis between DES and BMS at long-term follow-up. Patients receiving DES implantation appeared to have a lower 1-year incidence of recurrent myocardial infarction than those receiving BMS (RR = 0.75, 95% CI 0.56 to 1.00, p= 0.05). Moreover, the risk of target vessel revascularization (TVR) after receiving DES was consistently lowered during long-term observation (all p< 0.01). In subgroup analysis, the use of everolimus-eluting stents (EES) was associated with reduced risk of stent thrombosis in STEMI patients (RR = 0.37, p=0.02). Conclusions DES did not increase the risk of stent thrombosis in patients with STEMI compared with BMS. Moreover, the use of DES did lower long-term risk of repeat revascularization and might decrease the occurrence of reinfarction. PMID:25004414

  12. Impact of Insulin Resistance on Neointimal Tissue Proliferation after 2nd-Generation Drug-Eluting Stent Implantation.

    PubMed

    Komatsu, Takaaki; Yaguchi, Isao; Komatsu, Sachiko; Nakahara, Shiro; Kobayashi, Sayuki; Sakai, Yoshihiko; Taguchi, Isao

    2015-08-01

    Percutaneous coronary intervention is established as an effective treatment for patients with ischemic heart disease; in particular, drug-eluting stent implantation is known to suppress in-stent restenosis. Diabetes mellitus is an independent risk factor for restenosis, so reducing insulin resistance is being studied as a new treatment approach. In this prospective study, we sought to clarify the factors associated with in-stent restenosis after percutaneous coronary intervention, and we evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) index as a predictor of restenosis. We enrolled 136 consecutive patients who underwent elective percutaneous coronary intervention at our hospital from February 2010 through April 2013. All were implanted with a 2nd-generation drug-eluting stent. We distributed the patients in accordance with their HOMA-IR index values into insulin-resistant Group P (HOMA-IR, ≥2.5; n=77) and noninsulin-resistant Group N (HOMA-IR, <2.5; n=59). Before and immediately after stenting, we measured reference diameter, minimal lumen diameter, and percentage of stenosis, and after 8 months we measured the last 2 factors and late lumen loss, all by means of quantitative coronary angiography. After 8 months, the mean minimal lumen diameter was smaller in Group P than that in Group N (1.85 ± 1.02 vs 2.37 ± 0.66 mm; P=0.037), and the mean late lumen loss was larger (0.4 ± 0.48 vs 0.16 ± 0.21 mm; P=0.025). These results suggest that insulin resistance affects neointimal tissue proliferation after 2nd-generation drug-eluting stent implantation. PMID:26413014

  13. Impedance Changes and Fibrous Tissue Growth after Cochlear Implantation Are Correlated and Can Be Reduced Using a Dexamethasone Eluting Electrode

    PubMed Central

    Mugridge, Kenneth; Jolly, Claude; Fehr, Michael; Lenarz, Thomas; Scheper, Verena

    2016-01-01

    Background The efficiency of cochlear implants (CIs) is affected by postoperative connective tissue growth around the electrode array. This tissue formation is thought to be the cause behind post-operative increases in impedance. Dexamethasone (DEX) eluting CIs may reduce fibrous tissue growth around the electrode array subsequently moderating elevations in impedance of the electrode contacts. Methods For this study, DEX was incorporated into the silicone of the CI electrode arrays at 1% and 10% (w/w) concentration. Electrodes prepared by the same process but without dexamethasone served as controls. All electrodes were implanted into guinea pig cochleae though the round window membrane approach. Potential additive or synergistic effects of electrical stimulation (60 minutes) were investigated by measuring impedances before and after stimulation (days 0, 7, 28, 56 and 91). Acoustically evoked auditory brainstem responses were recorded before and after CI insertion as well as on experimental days 7, 28, 56, and 91. Additionally, histology performed on epoxy embedded samples enabled measurement of the area of scala tympani occupied with fibrous tissue. Results In all experimental groups, the highest levels of fibrous tissue were detected in the basal region of the cochlea in vicinity to the round window niche. Both DEX concentrations, 10% and 1% (w/w), significantly reduced fibrosis around the electrode array of the CI. Following 3 months of implantation impedance levels in both DEX-eluting groups were significantly lower compared to the control group, the 10% group producing a greater effect. The same effects were observed before and after electrical stimulation. Conclusion To our knowledge, this is the first study to demonstrate a correlation between the extent of new tissue growth around the electrode and impedance changes after cochlear implantation. We conclude that DEX-eluting CIs are a means to reduce this tissue reaction and improve the functional benefits of

  14. Combination of modified mixing technique and low frequency ultrasound to control the elution profile of vancomycin-loaded acrylic bone cement

    PubMed Central

    Wendling, A.; Mar, D.; Wischmeier, N.; Anderson, D.

    2016-01-01

    Objectives The objective of this study was to determine if combining variations in mixing technique of antibiotic-impregnated polymethylmethacrylate (PMMA) cement with low frequency ultrasound (LFUS) improves antibiotic elution during the initial high phase (Phase I) and subsequent low phase (Phase II) while not diminishing mechanical strength. Methods Three batches of vancomycin-loaded PMMA were prepared with different mixing techniques: a standard technique; a delayed technique; and a control without antibiotic. Daily elution samples were analysed using flow injection analysis (FIA). Beginning in Phase II, samples from each mix group were selected randomly to undergo either five, 15, 45, or 0 minutes of LFUS treatment. Elution amounts between LFUS treatments were analysed. Following Phase II, compression testing was done to quantify strength. A-priori t-tests and univariate ANOVAs were used to compare elution and mechanical test results between the two mix groups and the control group. Results The delayed technique showed a significant increase in elution on day one compared with the standard mix technique (p < 0.001). The transition point from Phase I to Phase II occurred on day ten. LFUS treatments significantly increased elution amounts for all groups above control. Delayed technique resulted in significantly higher elution amounts for the five-minute- (p = 0.004) and 45-minute- (p < 0.001) duration groups compared with standard technique. Additionally, the correlations between LFUS duration and total elution amount for both mix techniques were significant (p = 0.03). Both antibiotic-impregnated groups exhibited a significant decrease in offset yield stress compared with the control group (p < 0.001), however, their lower 95% confidence intervals were all above the 70 MPa limit defined by International Standards Organization (ISO) 5833-2 reference standard for acrylic bone cement. Conclusion The combination of a delayed mix technique with LFUS treatments

  15. Rapid quantitative method for the detection of phenylalanine and tyrosine in human plasma using pillar array columns and gradient elution.

    PubMed

    Song, Yanting; Takatsuki, Katsuya; Sekiguchi, Tetsushi; Funatsu, Takashi; Shoji, Shuichi; Tsunoda, Makoto

    2016-07-01

    This study reports a fast and quantitative determination method for phenylalanine (Phe) and tyrosine (Tyr) in human plasma using on-chip pressure-driven liquid chromatography. A pillar array column with low-dispersion turns and a gradient elution system was used. The separation of fluorescent derivatives of Phe, Tyr, and other hydrophobic amino acids was successfully performed within 140 s. Under the optimized conditions, Phe and Tyr in human plasma were quantified. The developed method is promising for rapid diagnosis in the clinical field.

  16. Black hole restenosis after drug-eluting stent implantation for in-stent restenosis: potential mechanism and optimal strategy.

    PubMed

    Otsuka, Yoritaka; Murata, Takashi; Kono, Michiaki; Imoto, Hiroki; Koyama, Taku; Nakamura, Keita; Kadama, Sunao; Noguchi, Hiroo; Saito, Taro

    2015-09-01

    In-stent restenosis (ISR) has long remained as the major limitation of coronary stenting. The use of drug-eluting stent (DES) reduces the risk of repeat revascularization without an increase of death and myocardial infarction, compared to the standard bare metal stents. DES has also demonstrated markedly to reduce ISR for complex lesions. However, ISR after DES implantation still occurs and optimal treatment for ISR after DES has not been established. Herein, we report 3 cases with black hole restenosis confirmed by intravascular ultrasound at the site of overlapped DES and discuss potential mechanism and optimal strategy for this phenomenon.

  17. Cost-Effectiveness of Percutaneous Coronary Intervention with Drug Eluting Stents versus Bypass Surgery for Patients with Diabetes and Multivessel Coronary Artery Disease: Results from the FREEDOM Trial

    PubMed Central

    Magnuson, Elizabeth A.; Farkouh, Michael E.; Fuster, Valentin; Wang, Kaijun; Vilain, Katherine; Li, Haiyan; Appelwick, Jaime; Muratov, Victoria; Sleeper, Lynn A.; Boineau, Robin; Abdallah, Mouin; Cohen, David J.

    2013-01-01

    Background Studies from the balloon angioplasty and bare metal stent eras have demonstrated that CABG is cost-effective compared with PCI for patients undergoing multivessel coronary revascularization—particularly among patients with complex CAD or diabetes. Whether these results apply in the drug-eluting stent (DES) era is unknown. Methods and Results Between 2005 and 2010, 1900 patients with diabetes and multivessel CAD were randomized to PCI with DES (DES-PCI; n=953) or CABG (n=947). Costs were assessed from the perspective of the U.S. health care system. Health state utilities were assessed using the EuroQOL. A patient-level microsimulation model based on U.S. life-tables and in-trial results was used to estimate lifetime cost-effectiveness. Although initial procedural costs were lower for CABG, total costs for the index hospitalization were $8,622/patient higher. Over the next 5 years, follow-up costs were higher with PCI, owing to more frequent repeat revascularization and higher outpatient medication costs. Nonetheless, cumulative 5-year costs remained $3,641/patient higher with CABG. Although there were only modest gains in survival with CABG during the trial period, when the in-trial results were extended to a lifetime horizon, CABG was projected to be economically attractive relative to DES-PCI, with substantial gains in both life expectancy and quality-adjusted life expectancy and incremental cost-effectiveness ratios <$10,000 per life-year or quality-adjusted life-year gained across a broad range of assumptions regarding the effect of CABG on post-trial survival and costs. Conclusions Despite higher initial costs, CABG is a highly cost-effective revascularization strategy compared with DES-PCI for patients with diabetes and multivessel CAD. PMID:23277307

  18. Microchip electrospray: improvements in spray and signal stability during gradient elution by an inverted postcolumn makeup flow.

    PubMed

    Jung, Stephanie; Effelsberg, Uwe; Tallarek, Ulrich

    2011-12-01

    Dynamic changes in mobile phase composition during high-performance liquid chromatography (HPLC) gradient elution coupled to mass spectrometry (MS) sensitively affect electrospray modes. We investigate the impact of the eluent composition on spray stability and MS response by infusion and injection experiments with a small tetrapeptide in water-acetonitrile mixtures. The employed HPLC/electrospray (ESI)-MS configuration uses a microchip equipped with an enrichment column, a separation column, and a makeup flow (MUF) channel. One nano pump is connected to the separation column, while a second one delivers solvent of exactly inverted composition to the MUF channel. Both solvent streams are united behind the separation column, before the ESI tip, such that the resulting electrosprayed solution always has identical composition during a gradient elution. Analyte peak parameters without and with MUF compensation are determined and discussed with respect to the electrospray mode and eluent composition. The postcolumn MUF significantly improves spray and signal stability over the entire solvent gradient, without compromising the performance of the HPLC separation column. It can also be conveniently implemented on microchip platforms.

  19. Development of a transparent, non-cytotoxic, silver ion-exchanged glass with antimicrobial activity and low ion elution.

    PubMed

    Shim, Gyu-In; Kim, Seong-Hwan; Eom, Hyung-Woo; Kim, Kwang-Mahn; Choi, Se-Young

    2015-05-01

    We investigated the antimicrobial, cytotoxicity, skin irritation, and ion elution behaviors of glass doped with silver ions with respect to its application to electronic equipment such as phones and tablet screens. The microbes tested were Escherichia coli, Staphylococcus aureus, and Penicillium funiculosum. AgNO3 powder was spread on both sides of aluminosilicate glass, and it was heated to 250-280°C for 10min. Under optimized heating conditions (260°C, 10min), the antimicrobial activity of ion-exchanged glass against bacteria and fungi was over 99.9% after 24 weeks. The glass failed to irritate the skin of experimental animals and was considered non-cytotoxic. The maximum amount of Ag ions that were eluted from the ion-exchanged glass into drinking water was measured at 0.037±0.003μgL(-1), an amount which is several orders of magnitude below the standard limit of 0.1mgL(-1) in drinking water. Ag ion-exchanged glass had characteristics suitable for use as a display screen, such as a light transmittance of 90% and a surface roughness of 0.704nm. Our findings suggest that glass doped with silver ions is more hygienic than non-doped glass is, and should be applied to display screens and glassware.

  20. Release mechanism and parameter estimation in drug-eluting stent systems: analytical solutions of drug release and tissue transport.

    PubMed

    McGinty, Sean; McKee, Sean; McCormick, Christopher; Wheel, Marcus

    2015-06-01

    Drug-eluting stents have significantly improved the treatment of coronary artery disease. They offer reduced rates of restenosis compared with their bare-metal predecessors and are the current gold standard in percutaneous coronary interventions. Drug-eluting stents have been approved for use in humans since 2002 and yet, despite the intensive research activity over the past decade, the drug release mechanism(s) and the uptake into the arterial wall are still poorly understood. While stent manufacturers have focussed primarily on empirical methods, several mathematical models have appeared in the literature considering the release problem, the uptake problem and also the coupled problem. However, two significant challenges that remain are in understanding the drug release mechanism(s) and also the determination of the various parameters characterizing the system. These include drug diffusion coefficients and dissolution constants in the stent polymer coating as well as drug diffusion coefficients, binding/uptake rates and the magnitude of the transmural convection in the arterial wall. In this paper we attempt to address these problems. We provide analytical solutions which, when compared with appropriate experiments, may allow the various parameters of the system to be estimated via the inverse problem. The analytical solutions which we provide here for drug release in vitro may thus be used as a tool for providing insights into the mechanism(s) of release.

  1. Application of hydrophilic interaction chromatography retention coefficients for predicting peptide elution with TFA and methanesulfonic acid ion-pairing reagents.

    PubMed

    Wujcik, Chad E; Tweed, Joseph; Kadar, Eugene P

    2010-03-01

    Hydrophilic retention coefficients for 17 peptides were calculated based on retention coefficients previously published for TSKgel silica-60 and were compared with the experimental elution profile on a Waters Atlantis HILIC silica column using TFA and methanesulfonic acid (MSA) as ion-pairing reagents. Relative peptide retention could be accurately determined with both counter-ions. Peptide retention and chromatographic behavior were influenced by the percent acid modifier used with increases in both retention and peak symmetry observed at increasing modifier concentrations. The enhancement of net peptide polarity through MSA pairing shifted retention out by nearly five-fold for the earliest eluting peptide, compared with TFA. Despite improvements in retention and efficiency (N(eff)) for MSA over TFA, a consistent reduction in calculated selectivity (alpha) was observed. This result is believed to be attributed to the stronger polar contribution of MSA masking and diminishing the underlying influence of the amino acid residues of each associated peptide. Finally, post-column infusion of propionic acid and acetic acid was evaluated for their potential to recover signal intensity for TFA and MSA counter-ions for LC-ESI-MS applications. Acetic acid generally yielded more substantial signal improvements over propionic acid on the TFA system while minimal benefits and some further reductions were noted with MSA.

  2. Analysis of Biological Samples Using Paper Spray Mass Spectrometry: An Investigation of Impacts by the Substrates, Solvents and Elution Methods

    PubMed Central

    Ren, Yue; Wang, He; Liu, Jiangjiang; Zhang, Zhiping; McLuckey, Morgan N.; Ouyang, Zheng

    2013-01-01

    Paper spray has been developed as a fast sampling ionization method for direct analysis of raw biological and chemical samples using mass spectrometry (MS). Quantitation of therapeutic drugs in blood samples at high accuracy has also been achieved using paper spray MS without traditional sample preparation or chromatographic separation. The paper spray ionization is a process integrated with a fast extraction of the analyte from the raw sample by a solvent, the transport of the extracted analytes on the paper, and a spray ionization at the tip of the paper substrate with a high voltage applied. In this study, the influence on the analytical performance by the solvent-substrate systems and the selection of the elution methods was investigated. The protein hemoglobin could be observed from fresh blood samples on silanized paper or from dried blood spots on silica-coated paper. The on-paper separation of the chemicals during the paper spray was characterized through the analysis of a mixture of the methyl violet 2B and methylene blue. The mode of applying the spray solvent was found to have a significant impact on the separation. The results in this study led to a better understanding of the analyte elution, on-paper separation, as well as the ionization processes of the paper spray. This study also help to establish a guideline for optimizing the analytical performance of paper spray for direct analysis of target analytes using mass spectrometry. PMID:24072932

  3. Microchip electrospray: improvements in spray and signal stability during gradient elution by an inverted postcolumn makeup flow.

    PubMed

    Jung, Stephanie; Effelsberg, Uwe; Tallarek, Ulrich

    2011-12-01

    Dynamic changes in mobile phase composition during high-performance liquid chromatography (HPLC) gradient elution coupled to mass spectrometry (MS) sensitively affect electrospray modes. We investigate the impact of the eluent composition on spray stability and MS response by infusion and injection experiments with a small tetrapeptide in water-acetonitrile mixtures. The employed HPLC/electrospray (ESI)-MS configuration uses a microchip equipped with an enrichment column, a separation column, and a makeup flow (MUF) channel. One nano pump is connected to the separation column, while a second one delivers solvent of exactly inverted composition to the MUF channel. Both solvent streams are united behind the separation column, before the ESI tip, such that the resulting electrosprayed solution always has identical composition during a gradient elution. Analyte peak parameters without and with MUF compensation are determined and discussed with respect to the electrospray mode and eluent composition. The postcolumn MUF significantly improves spray and signal stability over the entire solvent gradient, without compromising the performance of the HPLC separation column. It can also be conveniently implemented on microchip platforms. PMID:22022890

  4. Predictive elution window stretching and shifting as a generic search strategy for automated method development for liquid chromatography.

    PubMed

    Tyteca, Eva; Liekens, Anuschka; Clicq, David; Fanigliulo, Ameriga; Debrus, Benjamin; Rudaz, Serge; Guillarme, Davy; Desmet, Gert

    2012-09-18

    We report on the possibilities of a new method development (MD) algorithm that searches the chromatographic parameter space by systematically shifting and stretching the elution window over different parts of the time-axis. In this way, the search automatically focuses on the most promising areas of the solution space. Since only the retention properties of the first and last eluting compounds of the sample need to be (approximately) known, the algorithm can be directly applied to samples with unknown composition, and the proposed solutions are not sensitive to any modeling errors. The search efficiency of the algorithm has been evaluated on an extensive set of random-generated in silico samples covering a broad range of different retention properties. Compared to a pure grid-based search, the algorithm could reduce the number of missed components by 50% and more. The algorithm has also been applied to solve three different real-world separation problems from the pharmaceutical industry. All problems could be successfully solved in a very short time (order of 12 h of instrument time).

  5. Multivariate analysis applied to the study of spatial distributions found in drug-eluting stent coatings by confocal Raman microscopy.

    PubMed

    Balss, Karin M; Long, Frederick H; Veselov, Vladimir; Orana, Argjenta; Akerman-Revis, Eugena; Papandreou, George; Maryanoff, Cynthia A

    2008-07-01

    Multivariate data analysis was applied to confocal Raman measurements on stents coated with the polymers and drug used in the CYPHER Sirolimus-eluting Coronary Stents. Partial least-squares (PLS) regression was used to establish three independent calibration curves for the coating constituents: sirolimus, poly(n-butyl methacrylate) [PBMA], and poly(ethylene-co-vinyl acetate) [PEVA]. The PLS calibrations were based on average spectra generated from each spatial location profiled. The PLS models were tested on six unknown stent samples to assess accuracy and precision. The wt % difference between PLS predictions and laboratory assay values for sirolimus was less than 1 wt % for the composite of the six unknowns, while the polymer models were estimated to be less than 0.5 wt % difference for the combined samples. The linearity and specificity of the three PLS models were also demonstrated with the three PLS models. In contrast to earlier univariate models, the PLS models achieved mass balance with better accuracy. This analysis was extended to evaluate the spatial distribution of the three constituents. Quantitative bitmap images of drug-eluting stent coatings are presented for the first time to assess the local distribution of components. PMID:18510342

  6. Investigation of eluted monomers from resin-based root canal sealer by high-performance liquid chromatography analysis

    PubMed Central

    Omurlu, Huma; Arisu, Hacer Deniz; Dalkilic, Evrim Eliguzeloglu; Tamer, Ugur; Torul, Hilal

    2016-01-01

    Objective: The purpose of the current study was to determine the amount of urethane dimethacrylate (UDMA), bisphenol A-glycidyl methacrylate (Bis-GMA), poly (ethylene glycol) dimethacrylate (PEGDMA), bisphenol A ethoxylated dimethacrylate (Bis-EMA), and 2-hydroxyethyl methacrylate (HEMA) eluted from resin-based root canal sealer, epiphany, using high-performance liquid chromatography (HPLC). Materials and Methods: Epiphany was placed into the plastic molds and light-cured with a light emitting diode. After the curing process, each specimen in the first group (n = 12) was immersed in Eppendorf tubes containing a phosphate-buffered saline solution (PBS) and incubated for 45 s. In the second group, each specimen (n = 12) was immersed in Eppendorf tubes containing PBS and incubated for 24 h. Of the specimen extracts, 100 μL were subjected to HPLC. Analysis of data was accomplished with one-way analysis of variance (P < 0.05). Results: All of the samples eluted HEMA, UDMA, Bis-GMA, PEGDMA, and Bis-EMA. A significant difference was determined between the time periods of HEMA, UDMA, PEGDMA, and Bis-EMA (P < 0.05). Conclusion: The results of the current study showed that Epiphany releases HEMA, UDMA, Bis-GMA, PEGDMA, and Bis-EMA in both time periods. PMID:27011746

  7. Column Experiments for Radionuclide Adsorption Studies of the Culebra Dolomite: Retardation Parameter Estimation for Non-Eluted Actinide Species

    SciTech Connect

    Brown, G.O.; Lucero, D.A.; Perkins, W.G.

    1999-01-01

    brines. No significant changes in transport behavior were observed for changes in brine. Hydraulic characteristics (i.e., apparent porosity and apparent dispersion coefficient) for the cores were obtained via experiments using conservative tracer `Na. Elution experiments carried out over periods of a few days with tracers `*U and %Np indicated that these tracers were weakly retarded as indicated by delayed elution of these species. Elution experiments with tracers `%, 24'Pu, and 24'Ani were performed, but no elution of any of these species was observed in any flow experiment to date, including experiments of up to two years duration. However, B-Core was subjected to tomographic analysis from which a retardation factor can be inferred for%. Moreover, the fact of non- elution for 24*Pu and 24'Am after more than two years brine flow through C-Core can be coupled with the minimum detectable activity for each of these species to compute minimum retardation factors in C-Core. The retardation factors for all three species can then be coupled with the apparent hydraulic characteristics to estimate an apparent minimum solutionhock distribution coefficient, &, for each actinide. The specific radionuclide isotopes used in these experiments were chosen to facilitate analysis. Even though these isotopes are not necessarily the same as those that are most important to WIPP performance, they are isotopes of the same elements, and . their chemical and transport properties are therefore identical to those of isotopes in the WIPP inventory. The retardation factors and & values deduced from experimental results strongly support the contention that sorption in the Culebra provides an effective barrier to release of Th, Pu, and Am during the regulatory period.

  8. Development of simple and rapid elution methods for proteins from various affinity beads for their direct MALDI-TOF downstream application.

    PubMed

    Mlynarcik, Patrik; Bencurova, Elena; Madar, Marian; Mucha, Rastislav; Pulzova, Lucia; Hresko, Stanislav; Bhide, Mangesh

    2012-07-19

    Commercially available desalting techniques, necessary for downstream MALDI-TOF analysis of proteins, are often costly or time consuming for large-scale analysis. Here, we present techniques to elute proteins from various affinity resins, free from salt and ready for MALDI mass spectrometry. We showed that 0.1% TFA in 50% acetonitrile or 40% ethanol can be used as salt-free eluents for His-tagged proteins from variety of polyhistidine-affinity resins, while washing of resin beads twice with double-distilled water prior to the elution effectively desalted and recovered wide-range-molecular size proteins than commercially available desalting devices. Modified desalting and elution techniques were also applied for Flag- and Myc-tag affinity resins. The technique was further applied in co-precipitation assay, where the maximum recovery of wide-range molecular size proteins is crucial. Further, results showed that simple washing of the beads with double distilled water followed by elution with acetonitrile effectively desalted and recovered 150 kDa factor H protein of the sheep and its binding partner ~30 kDa BbCRASP-1 in co-precipitation assay. In summary, simple modifications in the desalting and elution strategy save time, labor and cost of the protein preparation for MALDI mass spectrometry; and large-scale protein purifications or co-precipitations can be performed with ease. PMID:22433248

  9. Rapid purification of calsequestrin from cardiac and skeletal muscle sarcoplasmic reticulum vesicles by Ca2+-dependent elution from phenyl-sepharose.

    PubMed

    Cala, S E; Jones, L R

    1983-10-10

    Treatment of cardiac or skeletal muscle sarcoplasmic reticulum vesicles with 0.1 M sodium carbonate selectively extracts both the Ca2+-binding protein calsequestrin and the two "intrinsic glycoproteins," while leaving the Ca2+-dependent ATPase membrane bound. Phenyl-Sepharose chromatography in the presence of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) and high salt (0.5 M NaCl) readily fractionates these solubilized proteins into a Ca2+-elutable fraction, which contains purified calsequestrin, and a low ionic strength elutable fraction, which contains one of the two intrinsic glycoproteins. Elution of calsequestrin from phenyl-Sepharose occurs near 1 mM Ca2+. Copurifying with calsequestrin are an homologous set of high molecular weight proteins, which like calsequestrin stain blue with Stains-All. These proteins are present in trace amounts and do not correspond to any sarcoplasmic reticulum proteins previously identified. Elution of calsequestrin from phenyl-Sepharose is consistent with the Ca2+-binding protein losing its hydrophobic character in the presence of millimolar Ca2+. This behavior is converse to that observed for several calmodulin-like proteins, which are eluted from hydrophobic gels in the presence of EGTA. The high yield and purity of calsequestrin prepared by this method makes possible a unique system for studying what may be a distinct class of Ca2+-binding proteins.

  10. Elution factors of synthetic oxotriacylglycerols as an aid in identification of peroxidized natural triacylglycerols by reverse-phase high-performance liquid chromatography with electrospray mass spectrometry.

    PubMed

    Sjövall, O; Kuksis, A; Marai, L; Myher, J J

    1997-11-01

    Selected elution factors were determined for model oxotriacylglycerols as an aid in identification of the peroxidation products of natural triacylglycerols by reverse-phase high-performance liquid chromatography (HPLC) with electrospray mass spectrometry (LC/ES/MS). For this purpose synthetic triacylglycerols of known structure were converted to hydroperoxides, hydroxides, epoxides, and core aldehydes and their dinitrophenylhydrazones by published procedures. The oxotriacylglycerols were resolved by normal-phase thin-layer chromatography and reverse-phase HPLC, and the identities of the oxotriacylglycerols confirmed by LC/ES/MS. Elution factors of oxotriacylglycerols were determined in relation to a homologous series of saturated triacylglycerols, ranging from 24 to 54 acyl carbons, and analyzed by reverse-phase HPLC, using a gradient of 20-80% isopropanol in methanol as eluting solvent and an evaporative light-scattering detector. It was shown that the elution times varied with the nature of the functional group and its regiolocation in the triacylglycerol molecule. A total of 31 incremental elution factors were calculated from chromatography of 33 oxygenated and nonoxygenated triacylglycerol species, ranging in carbon number from 36 to 54 and in double-bond number from 0 to 6.

  11. Increasing Confidence of LC-MS Identifications by Utilizing Ion Mobility Spectrometry

    SciTech Connect

    Crowell, Kevin L.; Baker, Erin Shammel; Payne, Samuel H.; Ibrahim, Yehia M.; Monroe, Matthew E.; Slysz, Gordon W.; Lamarche, Brian L.; Petyuk, Vladislav A.; Piehowski, Paul D.; Danielson, William F.; Anderson, Gordon A.; Smith, Richard D.

    2013-09-05

    Ion mobility spectrometry in conjunction with liquid chromatography separations and mass spectrometry offers a range of new possibilities for analyzing complex biological samples. To fully utilize the information obtained from these three measurement dimensions, informatics tools based on the accurate mass and time tag methodology were modified to incorporate ion mobility spectrometry drift times for peptides observed in human serum. A reference human serum database was created using 12,139 peptides, tracking the monoisotopic mass, liquid chromatography normalized elution time, and ion mobility spectrometry drift time(s) for each peptide. We demonstrate that the use of three dimensions for peak matching during the peptide identification process resulted in increased numbers of identifications and lower false discovery rates relative to the use of only the mass and normalized elution time dimensions.

  12. Controlling Your Utility Rates.

    ERIC Educational Resources Information Center

    Lucht, Ray; Dembowski, Frederick L.

    1985-01-01

    A cost-effective alternative to high utility bills for middle-sized and smaller utility users is the service of utility rate consultants. The consultants analyze utility invoices for the previous 12 months to locate available refunds or credits. (MLF)

  13. Neointimal tissue healing patterns after paclitaxel-eluting balloon treatment of in-stent restenosis: optical coherence tomography and intravascular ultrasound insights.

    PubMed

    Sandoval, Jorge; Medina, Miguel; Alfonso, Fernando

    2012-10-01

    An 80-year-old patient presented with severe in-stent restenosis of an everolimus-eluting stent implanted in the left anterior descending coronary artery 3 years previously. We obtained good angiographic result after paclitaxel-eluting balloon dilation. However, on optical coherence tomography (OCT), multiple, angiographically silent, in-stent, and edge-related dissections were readily recognized. Intravascular ultrasound (IVUS) revealed residual neointima with minor disruptions. At 9-month follow-up, an excellent angiographic result was demonstrated with complete resolution of the stent-related dissections on OCT. IVUS and OCT confirmed complete neointimal healing with a larger lumen. This case illustrates the value of OCT and IVUS to provide unique insights on the pathophysiological mechanisms and healing patterns of paclitaxel-eluting balloon treatment of in-stent restenosis.

  14. Resolution of co-eluting compounds of Cannabis Sativa in comprehensive two-dimensional gas chromatography/mass spectrometry detection with Multivariate Curve Resolution-Alternating Least Squares.

    PubMed

    Omar, Jone; Olivares, Maitane; Amigo, José Manuel; Etxebarria, Nestor

    2014-04-01

    Comprehensive Two Dimensional Gas Chromatography - Mass Spectrometry (GC × GC/qMS) analysis of Cannabis sativa extracts shows a high complexity due to the large variety of terpenes and cannabinoids and to the fact that the complete resolution of the peaks is not straightforwardly achieved. In order to support the resolution of the co-eluted peaks in the sesquiterpene and the cannabinoid chromatographic region the combination of Multivariate Curve Resolution and Alternating Least Squares algorithms was satisfactorily applied. As a result, four co-eluting areas were totally resolved in the sesquiterpene region and one in the cannabinoid region in different samples of Cannabis sativa. The comparison of the mass spectral profiles obtained for each resolved peak with theoretical mass spectra allowed the identification of some of the co-eluted peaks. Finally, the classification of the studied samples was achieved based on the relative concentrations of the resolved peaks. PMID:24607138

  15. One-step column chromatographic extraction with gradient elution followed by automatic separation of volatiles, flavonoids and polysaccharides from Citrus grandis.

    PubMed

    Han, Han-Bing; Li, Hui; Hao, Rui-Lin; Chen, Ya-Fei; Ni, He; Li, Hai-Hang

    2014-02-15

    Citrus grandis Tomentosa is widely used in traditional Chinese medicine and health foods. Its functional components include volatiles, flavonoids and polysaccharides which cannot be effectively extracted through traditional methods. A column chromatographic extraction with gradient elution was developed for one-step extraction of all bioactive substances from C. grandis. Dried material was loaded into a column with petroleum ether: ethanol (8:2, PE) and sequentially eluted with 2-fold PE, 3-fold ethanol: water (6:4) and 8-fold water. The elutes was separated into an ether fraction containing volatiles and an ethanol-water fraction containing flavonoids and polysaccharides. The later was separated into flavonoids and polysaccharides by 80% ethanol precipitation of polysaccharides. Through this procedure, volatiles, flavonoids and polysaccharides in C. grandis were simultaneously extracted at 98% extraction rates and simply separated at higher than 95% recovery rates. The method provides a simple and high-efficient extraction and separation of wide range bioactive substances.

  16. Resolution of co-eluting compounds of Cannabis Sativa in comprehensive two-dimensional gas chromatography/mass spectrometry detection with Multivariate Curve Resolution-Alternating Least Squares.

    PubMed

    Omar, Jone; Olivares, Maitane; Amigo, José Manuel; Etxebarria, Nestor

    2014-04-01

    Comprehensive Two Dimensional Gas Chromatography - Mass Spectrometry (GC × GC/qMS) analysis of Cannabis sativa extracts shows a high complexity due to the large variety of terpenes and cannabinoids and to the fact that the complete resolution of the peaks is not straightforwardly achieved. In order to support the resolution of the co-eluted peaks in the sesquiterpene and the cannabinoid chromatographic region the combination of Multivariate Curve Resolution and Alternating Least Squares algorithms was satisfactorily applied. As a result, four co-eluting areas were totally resolved in the sesquiterpene region and one in the cannabinoid region in different samples of Cannabis sativa. The comparison of the mass spectral profiles obtained for each resolved peak with theoretical mass spectra allowed the identification of some of the co-eluted peaks. Finally, the classification of the studied samples was achieved based on the relative concentrations of the resolved peaks.

  17. Simultaneous occlusion of left anterior descending and left circumflex arteries by very late stent thrombosis: vascular response to drug-eluting stents assessed by intravascular ultrasound.

    PubMed

    Yamawaki, Masahiro; Onuma, Yoshinobu; Nakano, Masatsugu; Muramatsu, Takashi; Nakatani, Shimpei; Ishibashi, Yuki; Ishimori, Hiroshi; Hirano, Keisuke; Ito, Yoshiaki; Tsukahara, Reiko; Muramatsu, Toshiya

    2015-11-01

    Very late stent thrombosis (VLST) is a catastrophic complication after implantation of a drug-eluting stent (DES). It has been reported that VLST is associated with pathological changes, which often include late acquired incomplete stent apposition (LAISA) with thrombus formation. In addition, the vascular response to the stent (evaginations, neointimal growth, and thrombosis) and the incidence of LAISA are reported to vary among the different types of DES. We experienced a patient with cardiogenic shock induced by simultaneous VLST of both the left anterior descending artery (LAD) and the left circumflex artery (LCX) at 3 years after implantation of two sirolimus-eluting stents. Intravascular ultrasound (IVUS) showed LAISA of both arteries. A paclitaxel-eluting stent, which had been implanted in the right coronary artery 3 years earlier, did not show such a finding. IVUS revealed "different vascular reactions" to "different types of DES" in this patient.

  18. A biodegradable antibiotic-eluting PLGA nanofiber-loaded deproteinized bone for treatment of infected rabbit bone defects.

    PubMed

    Gao, Jianting; Huang, Guofeng; Liu, Guojun; Liu, Yan; Chen, Qi; Ren, Lei; Chen, Changqing; Ding, Zhenqi

    2016-08-01

    We fabricated a biodegradable antibiotic-eluting poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (ANDB) scaffold that provided sustained delivery of vancomycin to repair methicillin-resistant Staphylococcus aureus bone defects. To fabricate the biodegradable ANDB, poly(d,l)-lactide-co-glycolide and vancomycin were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propano. The solution was then electrospun to produce biodegradable antibiotic-eluting membranes that were deposited on the surface of bovine deproteinized cancellous bone. We used scanning electron microscopy to determine the properties of the scaffold. Both elution and high-performance liquid chromatography assays were used to evaluate the in vitro vancomycin release rate from the ANDB scaffold. Three types of scaffolds were co-cultured with bacteria to confirm the in vitro antibacterial activity. The infected bone defect rabbit model was induced by injecting 10(7) colony forming units of a methicillin-resistant Staphylococcus aureus strain into the radial defect of rabbits. Animals were then separated into treatment groups and implanted according to the following scheme: ANDB scaffold in group A, poly(d,l)-lactide-co-glycolide nanofiber-loaded deproteinized bone (NDB) scaffold with intravenous (i.v.) vancomycin in group B, and NDB scaffold alone in group C. Treatment efficacy was evaluated after eight weeks using radiological, microbiological, and histological examinations. In vitro results revealed that biodegradable ANDB scaffolds released concentrations of vancomycin that were greater than the minimum inhibitory concentration for more than four weeks. Bacterial inhibition tests also confirmed antibacterial efficacy lasted for approximately four weeks. Radiological and histological scores obtained in vivo revealed significant differences between groups A, B and C. Importantly, group A had significantly lower bacterial load and better bone regeneration when compared to either group B

  19. Clinical Impact of Dual Antiplatelet Therapy Use in Patients Following Everolimus-eluting Stent Implantation: Insights from the SEEDS Study

    PubMed Central

    Zhang, Yao-Jun; Zhao, Ye-Lin; Xu, Bo; Han, Ya-Ling; Li, Bao; Liu, Qiang; Su, Xi; Pang, Si; Lu, Shu-Zheng; Guo, Xiao-Feng; Yang, Yue-Jin

    2015-01-01

    Background: Studies have suggested that use of prolonged dual antiplatelet therapy (DAPT) following new generation drug-eluting stent implantation may increase costs and potential bleeding events. This study aimed to investigate the association of DAPT status with clinical safety in patients undergoing everolimus-eluting stent (EES) implantation in the SEEDS study (A Registry to Evaluate Safety and Effectiveness of Everolimus Drug-eluting Stent for Coronary Revascularization) at 2-year follow-up. Methods: The SEEDS study is a prospective, multicenter study, where patients (n = 1900) with small vessel, long lesion, or multi-vessel diseases underwent EES implantation. Detailed DAPT status was collected at baseline, 6-month, 1- and 2-year. DAPT interruption was defined as any interruption of aspirin and/or clopidogrel more than 14 days. The net adverse clinical events (NACE, a composite endpoint of all-cause death, all myocardial infarction (MI), stroke, definite/probable stent thrombosis (ST), and major bleeding (Bleeding Academic Research Consortium II-V)) were investigated according to the DAPT status at 2-year follow-up. Results: DAPT was used in 97.8% of patients at 6 months, 69.5% at 12 months and 35.4% at 2 years. It was observed that the incidence of NACE was low (8.1%) at 2 years follow-up, especially its components of all-cause death (0.9%), stroke (1.1%), and definite/probable ST (0.7%). DAPT was not an independent predictor of composite endpoint of all-cause death/MI/stroke (hazard ratio [HR]: 0.693, 95% confidence interval [CI]: 0.096–4.980, P = 0.715) and NACE (HR: 1.041, 95% CI: 0.145–7.454, P = 0.968). Of 73 patients who had DAPT interruption, no patient had ST at 12-month, and only 1 patient experienced ST between 1- and 2-year (1.4%). There was a high frequency of major bleeding events (53/65, 82.5%) occurred in patients receiving DAPT treatment. Conclusions: Prolonged DAPT use was not associated with improved clinical safety. The study

  20. Antirestenotic Effects of a Novel Polymer-Coated D-24851 Eluting Stent. Experimental Data in a Rabbit Iliac Artery Model

    SciTech Connect

    Lysitsas, Dimitrios N.; Katsouras, Christos S.; Papakostas, John C.; Toumpoulis, Ioannis K.; Angelidis, Charalampos; Bozidis, Petros; Thomas, Christopher G.; Seferiadis, Konstantin; Psychoyios, Nikolaos; Frillingos, Stathis; Pavlidis, Nikolaos; Marinos, Euaggelos; Khaldi, Lubna; Sideris, Dimitris A.; Michalis, Lampros K.

    2007-11-15

    Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (dl-lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 {+-} 0.0025 {mu}M (31 {+-} 1 {mu}g; low dose; n = 7), 0.55 {+-} 0.02 {mu}M (216 {+-} 8 {mu}g; high dose; n = 6), and 4.55 {+-} 0.1 {mu}M (1774 {+-} 39 {mu}g; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.

  1. Low-dose sirolimus-eluting hydroxyapatite coating on stents does not increase platelet activation and adhesion ex vivo.

    PubMed

    Alviar, Carlos L; Tellez, Armando; Wang, Michael; Potts, Pamela; Smith, Doug; Tsui, Manus; Budzynski, Wladyslaw; Raizner, Albert E; Kleiman, Neal S; Lev, Eli I; Granada, Juan F; Kaluza, Greg L

    2012-07-01

    We previously found paclitaxel-eluting polymer-coated stents causing more human platelet-monocyte complex formation than bare metal stents in vitro. Presently, we examined patterns of platelet activation and adhesion after exposure to 6 nanofilm HAp-coated (HAp-nano) stents, 6 HAp-microporous-coated (HAp-micro) stents, 5 HAp sirolimus-eluting microporous-coated (HAp-SES) stents and 5 cobalt-chromium stents (BMS) deployed in an in vitro flow system. Blood obtained from healthy volunteers was circulated and sampled at 0, 10, 30 and 60 min. By flow cytometry, there were no significant differences in P-Selectin expression between the 4 stent types (HAp-nano = 32.5%; HAp-micro = 42.5%, HAp-SES = 10.23%, BMS = 7% change from baseline at 60 min, p = NS); PAC-1 antibody binding (HAp-nano = 11.8%; HAp-micro = 2.9%, HAp-SES = 18%, BMS = 6.4% change from baseline at 60 min, p = NS) or PMC formation (HAp-nano = 21.6%; HAp-micro = 4%, HAp-SES = 6.6%, BMS = 17.4% change from baseline at 60 min, p = NS). The 4 stent types did not differ in the average number of platelet clusters >10 μm in diameter by SEM (HAp-nano = 2.39 ± 5.75; HAp-micro = 2.26 ± 3.43; HAp-SES = 1.93 ± 3.24; BMS = 1.94 ± 2.41, p = NS). The majority of the struts in each stent group were only mildly covered by platelets, (HAp-nano = 80%, HAp-micro = 61%, HAp-SES = 78% and BMS = 52.1%, p = NS). The HAp-microporous-coated stents (ECD) attracted slightly more proteinaceous material than bare metal stents (HAp-micro = 35% struts with complete protein coverage, P < 0.0001 vs. other 3 stent types). In conclusion, biomimetic stent coating with nanofilm or microporous hydroxyapatite, even when eluting low-dose sirolimus, does not increase the platelet activation in circulating human blood, or platelet adhesion to stent surface when compared to bare metal stents in vitro.

  2. A field test of tracer transport and organic contaminant elution in a stratified aquifer at the Rocky Mountain Arsenal (Denver, Colorado, U.S.A.)

    NASA Astrophysics Data System (ADS)

    Thorbjarnarson, Kathryn W.; Mackay, Douglas M.

    1997-01-01

    A tracer-elution experiment was conducted in a 9-m-thick alluvial sand aquifer at the Rocky Mountain Arsenal, Denver, Colorado, within an extensive 1,1,1-trichloroethene and trichloroethene plume. The forced-gradient flow field was controlled by an injection well and an extraction well separated by 8.4 m and aligned in the direction of the natural-gradient flow. Upon extraction, the contaminant-laden water was treated by air stripping and reinjected into the injection well. Iodide tracer was added to the injection flow during the initial 27.5 h of the experiment. Tracer transport and organic contaminant elution were monitored by four 0.15-m-screened drive points and a fully penetrating monitoring well. Relative permeabilities, dispersivities and retardation factors were estimated from tracer breakthrough and contaminant elution curves by the moment method and by curve-fitting with an advection-dispersion model. Tracer transport through the four strata sampled by the drive points indicated a permeability variation of three orders of magnitude. Contaminant elution was not observed in the lowest-permeability stratum monitored during the experiment. In all monitored strata, contaminant elution was controlled primarily by permeability effects on water flow and exhibited minimal retardation or desorption effects. The fully penetrating monitoring well exhibited a tracer response primarily from the more permeable strata with the addition of tracer from the less permeable strata producing an increased breakthrough spreading. This increased spreading or dispersion was reflected in a higher longitudinal dispersivity estimate (1.2 m assuming a homogeneous aquifer) than dispersivity estimates from the drive-point sampler tracer curves (ranging from 5 to 21 cm). Contaminant elution curves from the fully penetrating monitoring well exhibited an initial response primarily from the more permeable strata (rapid elution of contaminants) and provided no insight into the elution

  3. Analytical modeling of drug dynamics induced by eluting stents in the coronary multi-layered curved domain.

    PubMed

    d'Errico, Michele; Sammarco, Paolo; Vairo, Giuseppe

    2015-09-01

    Pharmacokinetics induced by drug eluting stents (DES) in coronary walls is modeled by means of a one-dimensional multi-layered model, accounting for vessel curvature and non-homogeneous properties of the arterial tissues. The model includes diffusion mechanisms, advection effects related to plasma filtration through the walls, and bio-chemical drug reactions. A non-classical Sturm-Liouville problem with discontinuous coefficients is derived, whose closed-form analytical solution is obtained via an eigenfunction expansion. Soundness and consistency of the proposed approach are shown by numerical computations based on possible clinical treatments involving both hydrophilic and hydrophobic drugs. The influence of the main model parameters on drug delivery mechanisms is analyzed, highlighting the effects induced by vessel curvature and yielding comparative indications and useful insights into the concurring mechanisms governing the pharmacokinetics. PMID:26162517

  4. Chronic Total Occlusion and Successful Drug-Eluting Stent Placement in Takayasu Arteritis–Induced Renal Artery Stenosis

    PubMed Central

    Agarwal, Guarav; Vats, Hemender S.; Raval, Amish N.; Yevzlin, Alexander S.; Chan, Micah R.; Gimelli, Giorgio

    2013-01-01

    Takayasu arteritis-induced renal artery stenosis (TARAS) is a condition rarely described in the literature. Although percutaneous transluminal angioplasty and stenting has been well-described in the treatment of atherosclerotic renal artery stenosis, its role has not been established in non-atherosclerotic TARAS. We report a case of a female, age 17 years, with Takayasu arteritis who presented to the hospital with seizures and hypertensive crisis. A renal angiogram showed chronic total occlusion (CTO) of the left renal artery. Renal angioplasty and stenting was successfully performed after multiple attempts to deliver a wire distal to the CTO. After sequential balloon predilation, a drug-eluting stent was deployed, resulting in full reperfusion of the kidney. The patient’s blood pressure improved dramatically, and patency of the stent was demonstrated with magnetic resonance angiography over 9 months after the procedure. PMID:23656802

  5. DEVELOPMENT OF AN APPROACH TO MODELING LOADING AND ELUTION OF SPHERICAL RESORCINOL FORMALDEHYDE ION-EXCHANGE RESIN

    SciTech Connect

    Aleman, S.; Hamm, L.; Smith, F.

    2011-10-03

    The current strategy for removal of cesium from the Hanford waste stream is ion-exchange using spherical Resorcinol-Formaldehyde (sRF) resin. The original resin of choice was granular SuperLig 644 resin and during testing of this resin several operational issues were identified. For example, the granular material had a high angle of internal friction resulting in fragmentation of resin particles along its edges during cycling and adverse hydraulic performance. Efforts to replace SuperLig 644 were undertaken and one candidate was the granular Resorcinol-Formaldehyde (RF) resin where experience with this cation exchanger dates back to the late 1940's. To minimize hydraulic concerns a spherical version of RF was developed and several different chemically produced batches were created. The 5E-370/641 batch of sRF was selected and for the last decade numerous studies have been performed (e.g., batch contact tests, column loading and elution tests). The Waste Treatment Plant (WTP) flowsheet shows that the aqueous phase waste stream will have a wide range of ionic concentrations (e.g., during the loading step 0-3 M free OH, 5+ M Na, 0-1 M K, 0-3 M NO{sub 3}). Several steps are required in the ion-exchange process to achieve the required Cs separation factors: loading, displacement, washing, elution, and regeneration. The sRF resin will be operated over a wide range in pH (i.e., pH of 12-14 during the loading step and pH of 0.01-1 during the elution step). During some of these steps very high levels of counter-ions and co-ions will be present within the aqueous phase. Alternative process feeds are under consideration as well (e.g., sodium levels as high as 8 M and column operation up to 45 C during loading, reduced and recycled HNO{sub 3} during elution). In order to model the performance of sRF resin through an entire ion-exchange cycle, a more robust isotherm model is required. To achieve this more robust isotherm model requires knowledge of the numbers and kinds of

  6. Resolving co-eluting chromatographic patterns by means of dissimilarity analysis in iterative target transformation factor analysis.

    PubMed

    Zhang, Liangxiao; Zhang, Wan; Cao, Dongsheng; Zeng, Maomao; Liang, Yizeng; Kvalheim, Olav M

    2011-10-01

    The initialization of concentration vector for iterative target transformation factor analysis (ITTFA) and identification of pure or key variables are the important issue in MCR. In this study, dissimilarity analysis and evolving factor analysis (EFA) are combined to find the selective or key variables and subsequently obtain initial estimates of the concentration vectors for resolution of gas chromatography/mass spectrometry (GC/MS) data by ITTFA. For systems containing components with highly similar mass spectra, a new constraint setting the elements out of elution window to 0 is used to improve convergence rate and accuracy of results. Tested by standard mixture of two wax esters and real GC/MS data of gasoline 97#, dissimilarity based ITTFA could obtain accurate results (average Dot product of concentration vectors, average deviation of peak area ratio and average similarity of mass spectra are 0.9929, 0.0228 and 981.0, respectively). PMID:21880321

  7. Poly(styrenesulfonate)-Modified Ni-Ti Layered Double Hydroxide Film: A Smart Drug-Eluting Platform.

    PubMed

    Ge, Naijian; Wang, Donghui; Peng, Feng; Li, Jinhua; Qiao, Yuqin; Liu, Xuanyong

    2016-09-21

    Drug-eluting stents (DESs) are widely used in the palliative treatment of many kinds of cancers. However, the covered polymers used in DESs are usually associated with stent migration and acute cholecystitis. Therefore, developing noncovered drug-loading layers on metal stents is of great importance. In this work, Ni-Ti layered double hydroxide (Ni-Ti LDH) films were prepared on the surface of nitinol via hydrothermal treatment, and the LDH films were further modified by poly(styrenesulfonate) (PSS). The anticancer drug doxorubicin could be effectively loaded onto the modified films, and drug release could be smartly controlled by the pH. Besides, the drug absorption amounts of cancer cells cultured on the films could be effectively improved. These results indicate that the PSS-modified LDH film may become a promising drug-loading platform that can be used in the design of DESs. PMID:27579782

  8. Poly(styrenesulfonate)-Modified Ni-Ti Layered Double Hydroxide Film: A Smart Drug-Eluting Platform.

    PubMed

    Ge, Naijian; Wang, Donghui; Peng, Feng; Li, Jinhua; Qiao, Yuqin; Liu, Xuanyong

    2016-09-21

    Drug-eluting stents (DESs) are widely used in the palliative treatment of many kinds of cancers. However, the covered polymers used in DESs are usually associated with stent migration and acute cholecystitis. Therefore, developing noncovered drug-loading layers on metal stents is of great importance. In this work, Ni-Ti layered double hydroxide (Ni-Ti LDH) films were prepared on the surface of nitinol via hydrothermal treatment, and the LDH films were further modified by poly(styrenesulfonate) (PSS). The anticancer drug doxorubicin could be effectively loaded onto the modified films, and drug release could be smartly controlled by the pH. Besides, the drug absorption amounts of cancer cells cultured on the films could be effectively improved. These results indicate that the PSS-modified LDH film may become a promising drug-loading platform that can be used in the design of DESs.

  9. Therapeutic Effect of Akt1 siRNA Nanoparticle Eluting Coronary Stent on Suppression of Post-Angioplasty Restenosis.

    PubMed

    Che, Hui-Lian; Bae, In-Hi; Lim, Kyung Seob; Song, In Taek; Lee, Haeshin; Lee, Duhwan; Kim, Won Jong; Jeong, Myung-Ho; Ahn, Youngkeun

    2016-06-01

    For effective treatment of restenosis, therapeutic genes are delivered locally from a coated stent at the site of injury, leading to inhibition of smooth muscle proliferation and neo-intimal hyperplasia while promoting re-endothelialization. In a previous study, we delivered Akt1 siRNA nanoparticles (ASNs) from a hyaluronic acid (HA)-coated stent surface to specifically suppress the pro-proliferative Akt1 protein in smooth muscle cells (SMCs). In the present study, therapeutic efficacy was investigated in a rabbit restenosis model after percutaneous implantation of an ASN-immobilized stent in a rabbit iliac artery. Quantitative and qualitative analyses of in-stent restenosis were investigated in an in vivo animal model by micro-CT imaging and SEM observation, respectively. Proliferation status and neo-intima formation of the vascular tissues located near ASN-immobilized stents were analyzed by immunohistochemical staining using anti-Akt1 and anti-Ki67 antibodies and histological analyses, such as hematoxylin and eosin staining and Verhoeff's elastic stain. Re-endothelialization after implantation of an ASN-immobilized stent was also analyzed via immunohistochemistry using an anti-CD31 antibody. To elucidate the molecular mechanism related to reducing SMC proliferation and subsequent inhibition of in-stent restenosis in vivo, protein and mRNA expression of Akt1 and downstream signaling proteins were analyzed after isolating SMC-rich samples from the treated vasculature. The implanted Akt1 siRNA-eluting stent efficiently mitigated in-stent restenosis without any side effects and can be considered a successful substitute to current drug-eluting stents. PMID:27319215

  10. Simultaneous determination of captopril and hydrochlorothiazide in human plasma by reverse-phase HPLC from linear gradient elution.

    PubMed

    Huang, Taomin; He, Zhong; Yang, Bei; Shao, Luping; Zheng, Xiaowei; Duan, Gengli

    2006-05-01

    A simple, rapid and sensitive high-performance liquid chromatographic method for the simultaneous determination of captopril and hydrochlorothiazide in human plasma samples was developed. Captopril was derivatized with 2,4'-dibromoacetophenone (pBPB) to form a captopril-pBPB adduct. From acidified serum plasma samples, the hydrochlorothiazide and derivatized captopril was extracted with 5 ml ether, then with 5 ml dichloromethane. Effective chromatographic separation was achieved using a C(18) column (DIAMONSIL 150 mmx4 mm i.d., 5 microm) based on an acetonitrile-trifluoroacetic acid-water gradient elution at a flow rate of 1.2 ml/min. The internal standard (IS), derivatized captopril and hydrochlorothiazide were detected at 263 nm and were eluted at 4.2, 6.8 and 16.9 min, respectively. No endogenous substances were found to interfere. The limit of quantification for hydrochlorothiazide and derivatized captopril in plasma were 3.3 and 7 ng/ml. The calibration curve for derivatized captopril showed linearity in the range 20-4000 ng/ml, with a regression coefficient corresponding to 0.9993 and the coefficient of the variation of the points of the calibration curve being lower than 10%. The calibration curve for hydrochlorothiazide showed linearity in the range 10-1200 ng/ml, with a regression coefficient corresponding to 0.9999 and the coefficient of the variation of the points of the calibration curve being lower than 10%. The method was suitably validated and successfully applied to the determination of captopril and hydrochlorothiazide in human plasma samples.

  11. The development of point-of-use water filters as sampling devices in bioforensics: extent of microbial sorption and elution.

    PubMed

    Sedillo, Jennifer L; Quintana, Ayshea; Souza, Kathryn; Oshima, Kevin H; Smith, Geoffrey B

    2008-06-01

    The foundational idea for this project is that household faucet-mounted water filters may be used as bioforensic sampling devices to detect the extent of a potential bioagent release in domestic water supplies. An optimized eluent solution was determined experimentally by quantifying recoveries of microorganisms from point-of-use (POU) drinking water filters. The optimized extraction protocol was then used in mock bioagent release experiments to determine the feasibility of POU filters as bioforensic sampling devices. Bacillus atrophaeus spores, Escherichia coli and PP7 virus were exposed to filters and the number of attached organisms was determined by enumerating the unattached organisms on selective agar media. Subsequently, the filters were eluted and the percent of extracted organisms was determined based on the number of attached organisms. Two popular brands of carbon block filters retained 92%-99% of representative virus, spore and vegetative bacteria. In back-flush elutions of single filters, the most efficient eluent was identified as a combination of 1% peptone and 1% Tween-80, and extraction recovered 25.4% (+/-17.5%) of attached E. coli, 20.4% (+/-3.6%) of B. atrophaeus spores, and 9.4% (+/-5.2%) of PP7 virions (+/- standard deviations). In bioagent release studies in which filters were challenged with 100 agents mL(-1), greater than 99% of the spores were retained by the filters, and the percent of attached spores that were recovered ranged from 10.4% at day 0 to 4.3% five days after the release event (averaged from five separate experiments). In contrast, E. coli, Salmonella typhimurium and PP7 virus were rapidly inactivated in the chlorinated tap water, indicating their improbable survival in chlorinated water supplies. It is therefore concluded that household water filters can be used as microbial sampling devices for bioforensic applications in the event of a bioagent release in domestic drinking water supplies.

  12. Prospective study to evaluate safety and efficacy of Zotarolimus Eluting Stent (PSEZES) in patients with long coronary artery lesions

    PubMed Central

    Bahuleyan, C.G.; Krishna Kumar, V.V.; Babu, Shifas

    2015-01-01

    Background Although the safety and effectiveness of Drug-Eluting Stents (DES) has been established extensively, reports on long term clinical outcome with angiographic findings in patients with long coronary artery lesions are not many. Methods In this single-center prospective registry of 100 patients, a total of 110 denovo long lesions (>20 mm) were treated with Resolute Zotarolimus Eluting Stent (R-ZES). The patients were followed up clinically at 3, 6 and 12 months and follow up coronary angiography was performed at 9-months. The primary end point was one year rate of target lesion failure (TLF) which is a composite of cardiac death, target lesion myocardial infarction or ischemia driven target lesion revascularization (TLR). The secondary end points included definite or probable stent thrombosis, 9-month angiographic restenosis and late lumen loss. Results The mean age of patients was 58.7 ± 9.50 years with prevalence of diabetes as high as 60%. The mean lesion length was 24.67 ± 4.87 mm with a mean reference vessel diameter of 2.85 ± 0.32 mm and 67.3% were Type C lesions (ACC/AHA classification). Two patients died during follow-up, of which one was non-cardiac death. One patient had target vessel myocardial infarction and five patients (4.5%) had ischemia driven TLR. The incidence of TLF was 6.36%. Binary restenosis was seen in 7 out of 93 lesions (7.5%). Median late lumen loss at 9 month was 0.22 mm. No stent thrombosis was noted in the study. Conclusion Implantation of R-ZES in real-world patients with long coronary artery lesions is safe with comparable efficacy to what is observed in the treatment of less complex lesions. PMID:26138180

  13. Chromatographic models to predict the elution of ionizable analytes by organic modifier gradient in reversed phase liquid chromatography.

    PubMed

    Andrés, Axel; Téllez, Adolfo; Rosés, Martí; Bosch, Elisabeth

    2012-07-20

    The retention of an ionizable analyte under RP-HPLC organic modifier gradient elution is strongly affected by its ionization degree which, in turn, depends on its pK(a) and on the pH of the mobile phase. The values of both parameters change depending on the mobile phase composition and thus retention becomes a parameter quite difficult to predict, particularly when working in gradient mode. In this work, an equation describing the retention of ionizable analytes has been combined with three different models of different complexity, developed for gradient elution of neutral compounds (1, 2, or 3 fitting parameters), in order to predict retention of compounds with acid-base properties with particular buffers. All models have been tested under 16 different gradient patterns (4 linear gradients, 4 concave gradients, 4 convex gradients and 4 combinations between them) for the prediction of the retention time of 12 acid-base compounds (pK(a) values from 4 to 9) in 3 different buffered mobile phases (pH 5, pH 7 and pH 9) with acetonitrile as organic modifier. The agreement between the experimental and calculated retention times is good for all models. The best results are obtained through the model that depends on three parameters and the accuracy of the two-parameter model is slightly lower but very acceptable too. On the other hand, the predictions performed with the one-parameter model are the less accurate, but good enough to become a valid model taking into account that it requires very little experimental work.

  14. The development of point-of-use water filters as sampling devices in bioforensics: extent of microbial sorption and elution.

    PubMed

    Sedillo, Jennifer L; Quintana, Ayshea; Souza, Kathryn; Oshima, Kevin H; Smith, Geoffrey B

    2008-06-01

    The foundational idea for this project is that household faucet-mounted water filters may be used as bioforensic sampling devices to detect the extent of a potential bioagent release in domestic water supplies. An optimized eluent solution was determined experimentally by quantifying recoveries of microorganisms from point-of-use (POU) drinking water filters. The optimized extraction protocol was then used in mock bioagent release experiments to determine the feasibility of POU filters as bioforensic sampling devices. Bacillus atrophaeus spores, Escherichia coli and PP7 virus were exposed to filters and the number of attached organisms was determined by enumerating the unattached organisms on selective agar media. Subsequently, the filters were eluted and the percent of extracted organisms was determined based on the number of attached organisms. Two popular brands of carbon block filters retained 92%-99% of representative virus, spore and vegetative bacteria. In back-flush elutions of single filters, the most efficient eluent was identified as a combination of 1% peptone and 1% Tween-80, and extraction recovered 25.4% (+/-17.5%) of attached E. coli, 20.4% (+/-3.6%) of B. atrophaeus spores, and 9.4% (+/-5.2%) of PP7 virions (+/- standard deviations). In bioagent release studies in which filters were challenged with 100 agents mL(-1), greater than 99% of the spores were retained by the filters, and the percent of attached spores that were recovered ranged from 10.4% at day 0 to 4.3% five days after the release event (averaged from five separate experiments). In contrast, E. coli, Salmonella typhimurium and PP7 virus were rapidly inactivated in the chlorinated tap water, indicating their improbable survival in chlorinated water supplies. It is therefore concluded that household water filters can be used as microbial sampling devices for bioforensic applications in the event of a bioagent release in domestic drinking water supplies. PMID:18528538

  15. A Resorbable Antibiotic-Eluting Polymer Composite Bone Void Filler for Perioperative Infection Prevention in a Rabbit Radial Defect Model

    PubMed Central

    Brooks, Benjamin D.; Sinclair, Kristofer D.; Grainger, David W.; Brooks, Amanda E.

    2015-01-01

    Nearly 1.3 million total joint replacement procedures are performed in the United States annually, with numbers projected to rise exponentially in the coming decades. Although finite infection rates for these procedures remain consistently low, device-related infections represent a significant cause of implant failure, requiring secondary or revision procedures. Revision procedures manifest several-fold higher infection recurrence rates. Importantly, many revision surgeries, infected or not, require bone void fillers to support the host bone and provide a sufficient tissue bed for new hardware placement. Antibiotic-eluting bone void fillers (ABVF), providing both osteoconductive and antimicrobial properties, represent one approach for reducing rates of orthopedic device-related infections. Using a solvent-free, molten-cast process, a polymer-controlled antibiotic-eluting calcium carbonate hydroxyapatite (HAP) ceramic composite BVF (ABVF) was fabricated, characterized, and evaluated in vivo using a bacterial challenge in a rabbit radial defect window model. ABVF loaded with tobramycin eliminated the infectious burden in rabbits challenged with a clinically relevant strain of Staphylococcus aureus (inoculum as high as 107 CFU). Histological, microbiological, and radiographic methods were used to detail the effects of ABVF on microbial challenge to host bone after 8 weeks in vivo. In contrast to the HAP/BVF controls, which provided no antibiotic protection and required euthanasia 3 weeks post-operatively, tobramycin-releasing ABVF animals showed no signs of infection (clinical, microbiological, or radiographic) when euthanized at the 8-week study endpoint. ABVF sites did exhibit fibrous encapsulation around the implant at 8 weeks. Local antibiotic release from ABVF to orthopedic sites requiring bone void fillers eliminated the periprosthetic bacterial challenge in this 8-week in vivo study, confirming previous in vitro results. PMID:25815727

  16. Transport of Cryptosporidium parvum in porous media: Long-term elution experiments and continuous time random walk filtration modeling

    NASA Astrophysics Data System (ADS)

    Cortis, Andrea; Harter, Thomas; Hou, Lingling; Atwill, E. Robert; Packman, Aaron I.; Green, Peter G.

    2006-12-01

    Complex transport behavior other than advection-dispersion, simple retardation, and first-order removal has been observed in many biocolloid transport experiments in porous media. Such nonideal transport behavior is particularly evident in the late time elution of biocolloids at low concentrations. Here we present a series of saturated column experiments that were designed to measure the breakthrough and long-term elution of Cryptosporidium parvum in medium sand for a few thousand pore volumes after the initial source of oocysts was removed. For a wide range of ionic strengths, I, we consistently observe slower-than-Fickian, power law tailing. The slope of the tail is flatter for higher I. At very high ionic strength the slope decays to a rate slower than t-1. To explain this behavior, we propose a new filtration model based on the continuous time random walk (CTRW) theory. Our theory upscales heterogeneities at both the pore-scale geometry of the flow field and the grain surface physicochemical properties that affect biocolloid attachment and detachment. Pore-scale heterogeneities in fluid flow are shown to control the breakthrough of a conservative tracer but are shown to have negligible effect on oocyst transport. In our experiments, C. parvum transport is dominated by the effects of physicochemical heterogeneities. The CTRW model provides a parsimonious theory of nonreactive and reactive transport. The CTRW filtration process is controlled by three parameters, Λ, β, and c, which are related to the overall breakthrough retardation (R = 1 + Λ), the slope of the power law tail (β), and the transition to a slower than t-1 decay (c).

  17. Drug-eluting microarrays for cell-based screening of chemical-induced apoptosis

    PubMed Central

    Kwon, Cheong Hoon; Wheeldon, Ian; Kachouie, Nezamoddin N.; Lee, Seung Hwan; Bae, Hojae; Sant, Shilpa; Fukuda, Junji; Kang, Jeong Won; Khademhosseini, Ali

    2011-01-01

    Traditional high throughput screening (HTS) is carried out in centralized facilities that require extensive robotic liquid and plate handling equipment. This model of HTS is restrictive as such facilities are not accessible to many researchers. We have designed a simple microarray platform for cell-based screening that can be carried out at the bench top. The device creates a microarray of 2100 individual cell-based assays in a standard microscope slide format. A microarray of chemical-laden hydrogels addresses a matching array of cell-laden microwells thus creating a microarray of sealed microscale cell cultures each with unique conditions. We demonstrate the utility of the device by screening the extent of apoptosis and necrosis in MCF-7 breast cancer cells in response to exposure to a small library of chemical compounds. From a set of screens we produced a rank order of chemicals that preferentially induce apoptosis over necrosis in MCF-7 cells. Treatment with doxorubicin induced high levels of apoptosis in comparison with staurosporine, ethanol, and hydrogen peroxide, while treatment with 100 μM ethanol induced minimal apoptosis with high levels of necrosis. We anticipate broad application of the device for various research and discovery applications as it is easy to use, scalable and can be fabricated and operated with minimal peripheral equipment. PMID:21476591

  18. Molecular Mechanism of Local Drug Delivery with Paclitaxel-Eluting Membranes in Biliary and Pancreatic Cancer: New Application for an Old Drug

    PubMed Central

    Bang, Sookhee; Lee, Su Yeon; Baek, Yi-Yong; Yun, Jieun; Oh, Soo Jin; Lee, Chang Woo; Jo, Eun Ae; Yang, Sugeun; Lee, Don Haeng; Lee, Dong Ki

    2015-01-01

    Implantation of self-expanding metal stents (SEMS) is palliation for patients suffering from inoperable malignant obstructions associated with biliary and pancreatic cancers. Chemotherapeutic agent-eluting stents have been developed because SEMS are susceptible to occlusion by tumor in-growth. We reported recently that paclitaxel-eluting SEMS provide enhanced local drug delivery in an animal model. However, little is known about the molecular mechanisms by which paclitaxel-eluting stents attenuate tumor growth. We investigated the signal transduction pathways underlying the antiproliferative effects of a paclitaxel-eluting membrane (PEM) implanted in pancreatic/cholangiocarcinoma tumor bearing nude mice. Molecular and cellular alterations were analyzed in the PEM-implanted pancreatic/cholangiocarcinoma xenograft tumors by Western blot, immunoprecipitation, and immunofluorescence. The quantities of paclitaxel released into the tumor and plasma were determined by liquid chromatography-tandem mass spectroscopy. Paclitaxel from the PEM and its diffusion into the tumor inhibited angiogenesis, which involved suppression of mammalian target of rapamycin (mTOR) through regulation of hypoxia inducible factor (HIF-1) and increased apoptosis. Moreover, implantation of the PEM inhibited tumor-stromal interaction-related expression of proteins such as CD44, SPARC, matrix metalloproteinase-2, and vimentin. Local delivery of paclitaxel from a PEM inhibited growth of pancreatic/cholangiocarcinoma tumors in nude mice by suppressing angiogenesis via the mTOR and inducing apoptosis signal pathway. PMID:25983747

  19. A novel, multi-barrier, drug eluting calcium sulfate/biphasic calcium phosphate biodegradable composite bone cement for treatment of experimental MRSA osteomyelitis in rabbit model.

    PubMed

    Mistry, Surajit; Roy, Subhasis; Maitra, Nilendu Jyoti; Kundu, Biswanath; Chanda, Abhijit; Datta, Someswar; Joy, Mathew

    2016-10-10

    This article discloses the development of an effective and versatile technology to prepare a novel antibiotics-loaded biodegradable composite bone cement to treat methicillin-resistant Staphylococcal (MRSA) osteomyelitis and reports its detail in vitro characterization, drug loading efficiency, physico-mechanical properties, drug elution in simulated body fluid (SBF) and human plasma, merits and demerits over poly-methyl methacrylate (PMMA) cement. Chronic osteomyelitis in rabbit tibia (42) was induced by MRSA and composite cement was implanted to evaluate its safety and efficacy over PMMA cement and parenteral treated animals with histopathology, radiographs, bone/plasma drugs concentration, and SEM for 90days. The composite cement showed higher setting time, degradability, pH rise, injectability, in vitro drug elution but lesser mechanical strength than PMMA cement. Antibiotics release from cement beads was faster in SBF than plasma. Further, in vivo antibiotics elution from composite (42days) showed effective concentration against MRSA without eliciting drug-toxicity. Platelets activation by composite was an extraordinary feature. The in vivo studies also proved the superiority of composite cement than other treatment methods in terms of faster infection control and osteosynthesis. Based particularly on drug elution and in vivo results, this newly developed cement can successfully be used in clinical cases of chronic osteomyelitis.

  20. Evaluating misoprostol content in pregnant women with hourly oral administration during labor induction by microElution solid phase extraction combined with liquid chromatography tandem mass spectrometry.

    PubMed

    Hung, Cheng-Han; Cheng, Shi-Yann; Chan, Tzu-Min; Lee, Maw-Rong

    2015-09-01

    Misoprostol is a widely used alternative of prostaglandin for labor induction. Based on previous studies, we envision that small and frequent oral dosage of misoprostol is an effective method for labor induction. To monitor the misoprostol content during labor induction, a rapid, sensitive, and selective microElution solid phase extraction (μElution SPE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. Using μElution SPE could minimize the sample consumption and elution volume in order to maximize the sample enrichment and throughput. The misoprostol acid, a metabolite of misoprostol, was gradient separated in a Bidentate C18 column, then quantified by highly-selective reaction monitoring (H-SRM) in a total run time of 6min. The developed method was optimized and validated in human plasma, and showed linear range of 0.01-10ng/mL. The limit of detection (LOD) was 0.001ng/mL. The recovery ranged from 89.0 to 96.0%, and no significant matrix effect or carryover was observed. The precision, accuracy and stability were met with the criteria of U.S. FDA guidance. The developed method was successfully applied to evaluate misoprostol concentration during labor induction in pregnant women. The concentration-time profiles approves that hourly oral administration of misoprostol is a safe and effective method without drug accumulation for labor induction. PMID:26245361

  1. A novel, multi-barrier, drug eluting calcium sulfate/biphasic calcium phosphate biodegradable composite bone cement for treatment of experimental MRSA osteomyelitis in rabbit model.

    PubMed

    Mistry, Surajit; Roy, Subhasis; Maitra, Nilendu Jyoti; Kundu, Biswanath; Chanda, Abhijit; Datta, Someswar; Joy, Mathew

    2016-10-10

    This article discloses the development of an effective and versatile technology to prepare a novel antibiotics-loaded biodegradable composite bone cement to treat methicillin-resistant Staphylococcal (MRSA) osteomyelitis and reports its detail in vitro characterization, drug loading efficiency, physico-mechanical properties, drug elution in simulated body fluid (SBF) and human plasma, merits and demerits over poly-methyl methacrylate (PMMA) cement. Chronic osteomyelitis in rabbit tibia (42) was induced by MRSA and composite cement was implanted to evaluate its safety and efficacy over PMMA cement and parenteral treated animals with histopathology, radiographs, bone/plasma drugs concentration, and SEM for 90days. The composite cement showed higher setting time, degradability, pH rise, injectability, in vitro drug elution but lesser mechanical strength than PMMA cement. Antibiotics release from cement beads was faster in SBF than plasma. Further, in vivo antibiotics elution from composite (42days) showed effective concentration against MRSA without eliciting drug-toxicity. Platelets activation by composite was an extraordinary feature. The in vivo studies also proved the superiority of composite cement than other treatment methods in terms of faster infection control and osteosynthesis. Based particularly on drug elution and in vivo results, this newly developed cement can successfully be used in clinical cases of chronic osteomyelitis. PMID:27582374

  2. Fast Gradient Elution Reversed-Phase HPLC with Diode-Array Detection as a High Throughput Screening Method for Drugs of Abuse

    SciTech Connect

    Peter W. Carr; K.M. Fuller; D.R. Stoll; L.D. Steinkraus; M.S. Pasha; Glenn G. Hardin

    2005-12-30

    A new approach has been developed by modifying a conventional gradient elution liquid chromatograph for the high throughput screening of biological samples to detect the presence of regulated intoxicants. The goal of this work was to improve the speed of a gradient elution screening method over current approaches by optimizing the operational parameters of both the column and the instrument without compromising the reproducibility of the retention times, which are the basis for the identification. Most importantly, the novel instrument configuration substantially reduces the time needed to re-equilibrate the column between gradient runs, thereby reducing the total time for each analysis. The total analysis time for each gradient elution run is only 2.8 minutes, including 0.3 minutes for column reequilibration between analyses. Retention times standard calibration solutes are reproducible to better than 0.002 minutes in consecutive runs. A corrected retention index was adopted to account for day-to-day and column-to-column variations in retention time. The discriminating power and mean list length were calculated for a library of 47 intoxicants and compared with previous work from other laboratories to evaluate fast gradient elution HPLC as a screening tool.

  3. Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies.

    PubMed

    Hsu, Yung-Heng; Chen, Dave Wei-Chih; Tai, Chun-Der; Chou, Ying-Chao; Liu, Shih-Jung; Ueng, Steve Wen-Neng; Chan, Err-Cheng

    2014-01-01

    We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L)-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration) for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics.

  4. Evaluating misoprostol content in pregnant women with hourly oral administration during labor induction by microElution solid phase extraction combined with liquid chromatography tandem mass spectrometry.

    PubMed

    Hung, Cheng-Han; Cheng, Shi-Yann; Chan, Tzu-Min; Lee, Maw-Rong

    2015-09-01

    Misoprostol is a widely used alternative of prostaglandin for labor induction. Based on previous studies, we envision that small and frequent oral dosage of misoprostol is an effective method for labor induction. To monitor the misoprostol content during labor induction, a rapid, sensitive, and selective microElution solid phase extraction (μElution SPE) combined with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. Using μElution SPE could minimize the sample consumption and elution volume in order to maximize the sample enrichment and throughput. The misoprostol acid, a metabolite of misoprostol, was gradient separated in a Bidentate C18 column, then quantified by highly-selective reaction monitoring (H-SRM) in a total run time of 6min. The developed method was optimized and validated in human plasma, and showed linear range of 0.01-10ng/mL. The limit of detection (LOD) was 0.001ng/mL. The recovery ranged from 89.0 to 96.0%, and no significant matrix effect or carryover was observed. The precision, accuracy and stability were met with the criteria of U.S. FDA guidance. The developed method was successfully applied to evaluate misoprostol concentration during labor induction in pregnant women. The concentration-time profiles approves that hourly oral administration of misoprostol is a safe and effective method without drug accumulation for labor induction.

  5. A Global Information Utility.

    ERIC Educational Resources Information Center

    Block, Robert S.

    1984-01-01

    High-powered satellites, along with other existing technologies, make possible a world information utility that could distribute virtually limitless information to every point on earth. The utility could distribute information for business, government, education, and entertainment. How the utility would work is discussed. (RM)

  6. Paclitaxel-eluting stents versus sirolimus-eluting stents in patients with diabetes mellitus undergoing percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Wang, Hui-Bo; Zeng, Ping; Yang, Jun; Yang, Jian; Liu, Xiao-Wen

    2016-10-01

    Uncertainties exist with regard to the efficacy of paclitaxel-eluting stents (PES) versus sirolimus-eluting stents (SES) in diabetes patients undergoing percutaneous coronary intervention (PCI). We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the outcome of PES versus SES in diabetes patients undergoing PCI. A literature search was started, and we found all studies conducted from 2005 to 2016. We systematically searched the literature through the MEDLINE, Cochrane library, and EMBASE. Quality assessments were evaluated with the Jadad scale. Data were extracted considering the characteristics of efficacy and the safety of the designs. 12 RCTs satisfy the inclusion criteria. There is a significant decrease of target lesion revascularization (TLR) (MD = 0.65, 95 % CI = 0.42-1.00, P = 0.05) in a year and more than 1 year (MD = 0.54, 95 % CI = 0.37-0.78, P = 0.00010). A significant decrease of target vessel revascularization (TVR) in more than 1 year is (MD = 0.62, 95 % CI = 0.47-0.81, P = 0.0004). A significant decrease of major adverse cardiac events (MACE) in more than 1 year is (MD = 0.73, 95 % CI = 0.60-0.89, P = 0.002). Nevertheless, there is no significant difference in mortality (MD = 0.85, 95 % CI = 0.66-1.11, P = 0.24), stent thrombosis (ST) (MD = 0.65, 95 % CI = 0.35-1.21, P = 0.18), or myocardial infarction (MD = 1.04, 95 % CI = 0.71-1.51, P = 0.84). SES may be more significant in decreasing TLR, TVR, and MACE than PES without significantly increasing mortality, ST and MI in diabetes patients.

  7. Paclitaxel-eluting stents versus sirolimus-eluting stents in patients with diabetes mellitus undergoing percutaneous coronary intervention: a systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Wang, Hui-Bo; Zeng, Ping; Yang, Jun; Yang, Jian; Liu, Xiao-Wen

    2016-10-01

    Uncertainties exist with regard to the efficacy of paclitaxel-eluting stents (PES) versus sirolimus-eluting stents (SES) in diabetes patients undergoing percutaneous coronary intervention (PCI). We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the outcome of PES versus SES in diabetes patients undergoing PCI. A literature search was started, and we found all studies conducted from 2005 to 2016. We systematically searched the literature through the MEDLINE, Cochrane library, and EMBASE. Quality assessments were evaluated with the Jadad scale. Data were extracted considering the characteristics of efficacy and the safety of the designs. 12 RCTs satisfy the inclusion criteria. There is a significant decrease of target lesion revascularization (TLR) (MD = 0.65, 95 % CI = 0.42-1.00, P = 0.05) in a year and more than 1 year (MD = 0.54, 95 % CI = 0.37-0.78, P = 0.00010). A significant decrease of target vessel revascularization (TVR) in more than 1 year is (MD = 0.62, 95 % CI = 0.47-0.81, P = 0.0004). A significant decrease of major adverse cardiac events (MACE) in more than 1 year is (MD = 0.73, 95 % CI = 0.60-0.89, P = 0.002). Nevertheless, there is no significant difference in mortality (MD = 0.85, 95 % CI = 0.66-1.11, P = 0.24), stent thrombosis (ST) (MD = 0.65, 95 % CI = 0.35-1.21, P = 0.18), or myocardial infarction (MD = 1.04, 95 % CI = 0.71-1.51, P = 0.84). SES may be more significant in decreasing TLR, TVR, and MACE than PES without significantly increasing mortality, ST and MI in diabetes patients. PMID:27631549

  8. First-Generation Versus Second-Generation Drug-Eluting Stents in Coronary Chronic Total Occlusions: Two-Year Results of a Multicenter Registry

    PubMed Central

    Yu, Cheol Woong; Kim, Je Sang; Lee, Hyun Jong; Choi, Rak Kyeong; Kim, Tae Hoon; Jang, Ho Joon; Choi, Young Jin; Roh, Young Moo; Shim, Won-Heum; Song, Young Bin; Hahn, Joo-Yong; Choi, Jin-Ho; Lee, Sang Hoon; Gwon, Hyeon-Cheol; Choi, Seung-Hyuk

    2016-01-01

    Background Limited data are available regarding the long-term clinical outcomes of second-generation drug-eluting stents (DES) versus first-generation DES in patients with coronary chronic total occlusion (CTO) who undergo percutaneous coronary intervention (PCI). The aim of this study was to compare the clinical outcomes of second-generation DES with those of first-generation DES for the treatment of CTO. Methods and Results Between March 2003 and February 2012, 1,006 consecutive patients with CTO who underwent successful PCI using either first-generation DES (n = 557) or second-generation DES (n = 449) were enrolled in a multicenter, observational registry. Propensity-score matching was also performed. The primary outcome was cardiac death over a 2-year follow-up period. No significant differences were observed between the two groups regarding the incidence of cardiac death (first-generation DES versus second-generation DES; 2.5% vs 2.0%; hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.37 to 1.98; p = 0.72) or major adverse cardiac events (MACE, 11.8% vs 11.4%; HR: 1.00; 95% CI: 0.67 to 1.50; p = 0.99). After propensity score matching, the incidences of cardiac death (HR: 0.86; 95% CI: 0.35 to 2.06; p = 0.86) and MACE (HR: 0.93; 95% CI: 0.63 to 1.37; p = 0.71) were still similar in both groups. Furthermore, no significant differences were observed between sirolimus-eluting, paclitaxel-eluting, zotarolimus-eluting, and everolimus-eluting stents regarding the incidence of cardiac death or MACE. Conclusion This study shows that the efficacy of second-generation DES is comparable to that of first-generation DES for treatment of CTO over 2 years of follow-up. PMID:27314589

  9. Clinical utility of platinum chromium bare-metal stents in coronary heart disease

    PubMed Central

    Jorge, Claudia; Dubois, Christophe

    2015-01-01

    Coronary stents represent a key development for the treatment of obstructive coronary artery disease since the introduction of percutaneous coronary intervention. While drug-eluting stents gained wide acceptance in contemporary percutaneous coronary intervention practice, further developments in bare-metal stents remain crucial for patients who are not candidates for drug-eluting stents, or to improve metallic platforms for drug elution. Initially, stent platforms used biologically inert stainless steel, restricting stent performance due to limitations in flexibility and strut thickness. Later, cobalt chromium stent alloys outperformed steel as the material of choice for stents, allowing latest generation stents to be designed with significantly thinner struts, while maintaining corrosion resistance and radial strength. Most recently, the introduction of the platinum chromium alloy refined stent architecture with thin struts, high radial strength, conformability, and improved radiopacity. This review will provide an overview of the novel platinum chromium bare-metal stent platforms available for coronary intervention. Mechanical properties, clinical utility, and device limitations will be summarized and put into perspective. PMID:26345228

  10. Clinical utility of platinum chromium bare-metal stents in coronary heart disease.

    PubMed

    Jorge, Claudia; Dubois, Christophe

    2015-01-01

    Coronary stents represent a key development for the treatment of obstructive coronary artery disease since the introduction of percutaneous coronary intervention. While drug-eluting stents gained wide acceptance in contemporary percutaneous coronary intervention practice, further developments in bare-metal stents remain crucial for patients who are not candidates for drug-eluting stents, or to improve metallic platforms for drug elution. Initially, stent platforms used biologically inert stainless steel, restricting stent performance due to limitations in flexibility and strut thickness. Later, cobalt chromium stent alloys outperformed steel as the material of choice for stents, allowing latest generation stents to be designed with significantly thinner struts, while maintaining corrosion resistance and radial strength. Most recently, the introduction of the platinum chromium alloy refined stent architecture with thin struts, high radial strength, conformability, and improved radiopacity. This review will provide an overview of the novel platinum chromium bare-metal stent platforms available for coronary intervention. Mechanical properties, clinical utility, and device limitations will be summarized and put into perspective. PMID:26345228

  11. Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction

    PubMed Central

    Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

    2016-01-01

    Abstract Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI. From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses. The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina. Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy

  12. Aspiration Thrombectomy and Drug-Eluting Stent Implantation Decrease the Occurrence of Angina Pectoris One Year After Acute Myocardial Infarction.

    PubMed

    Lee, Wei-Chieh; Fang, Chih-Yuan; Chen, Huang-Chung; Hsueh, Shu-Kai; Chen, Chien-Jen; Yang, Cheng-Hsu; Yip, Hon-Kan; Hang, Chi-Ling; Wu, Chiung-Jen; Fang, Hsiu-Yu

    2016-04-01

    Angina pectoris is a treatable symptom that is associated with mortality and decreased quality of life. Angina eradication is a primary care goal of care after an acute myocardial infarction (AMI). Our aim was to evaluate factors influencing angina pectoris 1 year after an AMI.From January 2005 to December 2013, 1547 patient received primary percutaneous intervention in our hospital for an acute ST-segment elevation myocardial infarction (MI). Of these patients, 1336 patients did not experience post-MI angina during a 1-year follow-up, and 211 patients did. Univariate and multivariate logistic regression analyses were performed to identify the factors influencing angina pectoris 1 year after an AMI. Propensity score matched analyses were performed for subgroups analyses.The average age of the patients was 61.08 ± 12.77 years, with a range of 25 to 97 years, and 82.9% of the patients were male. During 1-year follow-up, 13.6% of the patients experienced post-MI angina. There was a longer chest pain-to-reperfusion time in the post-MI angina group (P = 0.01), as well as a higher fasting sugar level, glycohemoglobin (HbA1C), serum creatinine, troponin-I and creatine kinase MB (CK-MB). The post-MI angina group also had a higher prevalence of multiple-vessel disease. Manual thrombectomy, and distal protective device and intracoronary glycoprotein IIb/IIIa inhibitor injection were used frequently in the no post-MI angina group. Antiplatelet agents and post-MI medication usage were similar between the 2 groups. Multivariate logistic regression analyses demonstrated that prior MI was a positive independent predictor of occurrence of post-MI angina. Manual thrombectomy use and drug-eluting stent implantation were negative independent predictors of post-MI angina. Higher troponin-I and longer chest pain-to-reperfusion time exhibited a trend toward predicting post-MI angina.Prior MIs were strong, independent predictors of post-MI angina. Manual thrombectomy and drug-eluting

  13. A Combination of Drug-Eluting Stents and Bioresorbable Vascular Scaffolds in the Treatment of Multivessel Coronary Artery Disease

    PubMed Central

    Al-Mamary, Ahmed; Zilio, Filippo; Napodano, Massimo

    2016-01-01

    Optimal management of multivessel coronary artery disease can be complex. We report a 67-year-old male patient who was admitted to the Padua University Hospital, Padua, Italy, in 2014 with a non-ST-elevation myocardial infarction. Coronary angiography showed diffuse multiple sub-occlusive lesions of the proximal and distal left coronary vessels involving a long segment of the vessel. On intravascular ultrasonography (IVUS), the left main artery was moderately diseased with critically stenotic and calcified branch ostia. A successful percutaneous coronary intervention using the T-stenting and small protrusion technique with two drug-eluting stents (DES) was performed on the left main artery and its main branches. Two bioresorbable vascular scaffolds were also deployed in overlap at the mid to distal segments of the left anterior descending artery and overlapping a previous DES at the proximal segment. The full expansion and apposition of the struts and scaffolds to the vessel wall without residual stenosis was confirmed by IVUS.

  14. Intracoronary brachytherapy following drug-eluting stent failure It's still not time to hang up the spikes{exclamation_point}

    SciTech Connect

    Angiolillo, Dominick J.; Sabate, Manel; Jimenez-Quevedo, Pilar; Alfonso, Fernando; Galvan, Carmen; Fernandez, Jose Miguel; Hernandez-Antolin, Rosana; Escaned, Javier; Banuelos, Camino; Moreno, Raul; Macaya, Carlos

    2003-12-01

    Drug-eluting stents (DES) have significantly reduced the incidence of restenosis. Although the results obtained with these novel antiproliferative devices are encouraging, recent reports have shown that DES are not completely immune from restenosis. Therefore, the broad use of DES has inevitably led to a major issue: treatment of DES failure. Intracoronary brachytherapy (IBT) represents an important advancement for treatment of in-stent restenosis (ISR) and has led to important pathophysiological insight on the restenotic process. To date, IBT, when properly used, still represents the gold standard for treatment of ISR. However, experience with IBT is for treatment of ISR occurring with bare metal stents (BMS). Whether IBT may be used with the same safety and efficacy profile as an adjunctive treatment for ISR following DES implantation is still unknown. In this article, we report the outcome of a series of patients with DES failure treated with IBT. IBT for treatment of DES failure was shown to be both safe and efficient and, therefore, until ISR exists, IBT still remains an important player in this growing and even more challenging setting.

  15. The Tradeoff Between Shorter and Longer Courses of Dual Antiplatelet Therapy After Implantation of Newer Generation Drug-Eluting Stents.

    PubMed

    Bittl, John A

    2016-01-01

    The benefit of prolonged dual antiplatelet therapy (DAPT) after implantation of drug-eluting stents (DESs) remains uncertain. In 10 randomized controlled trials (RCTs) of 31,666 predominantly low-risk patients undergoing DES implantation, shorter courses (3-12 months) of DAPT resulted in lower mortality (odds ratio [OR] 0.83, 95 % confidence interval [CI] 0.69-0.98) and major hemorrhage (OR 0.60, 95 % CI 0.48-0.75) but increased myocardial infarction (MI, OR 1.34, 95 % CI 1.04-1.73) and stent thrombosis (ST, OR 1.75, 95 % CI 1.08-2.82) than did longer courses (12-36 months) of DAPT. A risk-benefit analysis identified 3 fewer deaths and 5 fewer bleeds but 4 more MIs and 3 more STs annually for every 1000 patients treated with the shorter courses. In the predominantly low-risk population enrolled in RCTs, limiting DAPT to 3 to 12 months after DES implantation saved lives and prevented bleeding at the expense of increased ST and MI. PMID:26732901

  16. Elution by Le Chatelier's principle for maximum recyclability of adsorbents: applied to polyacrylamidoxime adsorbents for extraction of uranium from seawater.

    PubMed

    Oyola, Yatsandra; Vukovic, Sinisa; Dai, Sheng

    2016-05-28

    Amidoxime-based polymer adsorbents have attracted interest within the last decade due to their high adsorption capacities for uranium and other rare earth metals from seawater. The ocean contains an approximated 4-5 billion tons of uranium and even though amidoxime-based adsorbents have demonstrated the highest uranium adsorption capacities to date, they are still economically impractical because of their limited recyclability. Typically, the adsorbed metals are eluted with a dilute acid solution that not only damages the amidoxime groups (metal adsorption sites), but is also not strong enough to remove the strongly bound vanadium, which decreases the adsorption capacity with each cycle. We resolved this challenge by incorporating Le Chatelier's principle to recycle adsorbents indefinitely. We used a solution with a high concentration of amidoxime-like chelating agents, such as hydroxylamine, to desorb nearly a 100% of adsorbed metals, including vanadium, without damaging the metal adsorption sites and preserving the high adsorption capacity. The method takes advantage of knowing the binding mode between the amidoxime ligand and the metal and mimics it with chelating agents that then in a Le Chatelier's manner removes metals by shifting to a new chemical equilibrium. For this reason the method is applicable to any ligand-metal adsorbent and it will make an impact on other extraction technologies. PMID:27117598

  17. Diphenylalanine peptide nanotubes self-assembled on functionalized metal surfaces for potential application in drug-eluting stent.

    PubMed

    Zohrabi, Tayebeh; Habibi, Neda; Zarrabi, Ali; Fanaei, Maryam; Lee, Lai Yeng

    2016-09-01

    This study focuses on the potential of diphenylalanine self-assembled peptide nanotubes (FF Nts) for delivery of flufenamic acid (FA) from metal implants. Self-assembly of FF Nts was studied in solution and on surfaces of glass, silicone and gold substrates. FA was loaded inside the shell of FF Nts and subsequently FF/FA Nts were attached to gold surfaces. The substrate were characterized by Field Emission Scanning Electron Microscopy (FESEM), fluorescence microscopy, confocal microscopy, and UV-vis spectroscopy. Release of FA from FF Nts were investigated by immersing coated metal substrates in phosphate-buffered saline for 12 days. Self-assembly of FF in water and solvent resulted in formation of nanotubes, which efficiently loaded 98% of FA with concentration of 20 µg/mL. FESEM images confirmed successful attachment of FF/FA Nts to functionalized gold substrates. In vitro release studies indicated using FF Nts has prolonged the release rate of FA for several days. Biocompatibility studied confirmed more than 50% of the cells were alive in concentration of 250-1000 µg/mL of FF Nts thus suggesting the potential of peptide based self-assemble nanostructures as an alternate system for polymer coating in drugs eluting stents. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2280-2290, 2016.

  18. A Combination of Drug-Eluting Stents and Bioresorbable Vascular Scaffolds in the Treatment of Multivessel Coronary Artery Disease.

    PubMed

    Al-Mamary, Ahmed; Zilio, Filippo; Napodano, Massimo

    2016-08-01

    Optimal management of multivessel coronary artery disease can be complex. We report a 67-year-old male patient who was admitted to the Padua University Hospital, Padua, Italy, in 2014 with a non-ST-elevation myocardial infarction. Coronary angiography showed diffuse multiple sub-occlusive lesions of the proximal and distal left coronary vessels involving a long segment of the vessel. On intravascular ultrasonography (IVUS), the left main artery was moderately diseased with critically stenotic and calcified branch ostia. A successful percutaneous coronary intervention using the T-stenting and small protrusion technique with two drug-eluting stents (DES) was performed on the left main artery and its main branches. Two bioresorbable vascular scaffolds were also deployed in overlap at the mid to distal segments of the left anterior descending artery and overlapping a previous DES at the proximal segment. The full expansion and apposition of the struts and scaffolds to the vessel wall without residual stenosis was confirmed by IVUS. PMID:27606119

  19. Improved peptide elution time prediction for reversed-phase liquid chromatography-MS by incorporating peptide sequence information

    SciTech Connect

    Petritis, Konstantinos; Kangas, Lars J.; Yan, Bo; Monroe, Matthew E.; Strittmatter, Eric F.; Qian, Weijun; Adkins, Joshua N.; Moore, Ronald J.; Xu, Ying; Lipton, Mary S.; Camp, David G.; Smith, Richard D.

    2006-07-15

    We describe an improved artificial neural network (ANN)-based method for predicting peptide retention times in reversed phase liquid chromatography. In addition to the peptide amino acid composition, this study investigated several other peptide descriptors to improve the predictive capability, such as peptide length, sequence, hydrophobicity and hydrophobic moment, and nearest neighbor amino acid, as well as peptide predicted structural configurations (i.e., helix, sheet, coil). An ANN architecture that consisted of 1052 input nodes, 24 hidden nodes, and 1 output node was used to fully consider the amino acid residue sequence in each peptide. The network was trained using {approx}345,000 non-redundant peptides identified from a total of 12,059 LC-MS/MS analyses of more than 20 different organisms, and the predictive capability of the model was tested using 1303 confidently identified peptides that were not included in the training set. The model demonstrated an average elution time precision of {approx}1.5% and was able to distinguish among isomeric peptides based upon the inclusion of peptide sequence information. The prediction power represents a significant improvement over our earlier report (Petritis et al., Anal. Chem. 2003, 75, 1039-1048) and other previously reported models.

  20. A Combination of Drug-Eluting Stents and Bioresorbable Vascular Scaffolds in the Treatment of Multivessel Coronary Artery Disease

    PubMed Central

    Al-Mamary, Ahmed; Zilio, Filippo; Napodano, Massimo

    2016-01-01

    Optimal management of multivessel coronary artery disease can be complex. We report a 67-year-old male patient who was admitted to the Padua University Hospital, Padua, Italy, in 2014 with a non-ST-elevation myocardial infarction. Coronary angiography showed diffuse multiple sub-occlusive lesions of the proximal and distal left coronary vessels involving a long segment of the vessel. On intravascular ultrasonography (IVUS), the left main artery was moderately diseased with critically stenotic and calcified branch ostia. A successful percutaneous coronary intervention using the T-stenting and small protrusion technique with two drug-eluting stents (DES) was performed on the left main artery and its main branches. Two bioresorbable vascular scaffolds were also deployed in overlap at the mid to distal segments of the left anterior descending artery and overlapping a previous DES at the proximal segment. The full expansion and apposition of the struts and scaffolds to the vessel wall without residual stenosis was confirmed by IVUS. PMID:27606119

  1. Surface immobilization of chondroitin 6-sulfate/heparin multilayer on stainless steel for developing drug-eluting coronary stents.

    PubMed

    Huang, Li-Ying; Yang, Ming-Chien

    2008-01-15

    A thin layer of gold was sputtered onto SUS316L stainless steel (SS) sheet. After thiolizing the Au layer with dimercaptosuccinic acid (DMSA), layers of chondroitin 6-sulfate (ChS) and heparin (HEP) were alternatively immobilized on the Au-treated SS. The resulting stent would be both anti-atherogenic and anti-thrombogenic. After repeating one to five cycles, one to five layers of polyelectrolyte complex (PEC) of ChS/HEP were successfully fabricated. A model drug, sirolimus, was loaded in the ChS/HEP layers. The SS-ChS-HEP surface was examined by X-ray photoelectron spectroscopy (XPS), contact angle, and atomic force microscopy (AFM) measurement. Biological tests including hemocompatibility, drug release pattern, and the inhibition of smooth muscle cell proliferation were also performed. The results show that the multilayer of ChS/HEP exhibits longer blood clotting time than pure SS substrates. Therefore, this biopolymer multilayer can avoid thrombosis on the stainless. The releasing rate of sirolimus can be controlled through the number of ChS/HEP PEC layers. With a five-layer coating, sirolimus can be released continuously for more than 20 days. Furthermore, the multilayer ChS/HEP loaded with sirolimus can suppress specifically to the growth of smooth muscle cells to avoid restenosis. This suggests that the PEC multilayer of ChS/HEP modified-SS could be applied in making drug-eluting stents. PMID:17720460

  2. In vitro elution of vancomycin from biodegradable osteoconductive calcium phosphate-polycaprolactone composite beads for treatment of osteomyelitis.

    PubMed

    Makarov, C; Cohen, V; Raz-Pasteur, A; Gotman, I

    2014-10-01

    In this work, osteoconductive composite materials comprising a large volume fraction of a bioresorbable calcium phosphate ceramic (CaP) and a smaller amount of a polycaprolactone polymer (PCL) were studied as a degradable antibiotic carrier material for treatment of osteomyelitis. Beads loaded with 1 and 4wt.% vancomycin were prepared by admixing dissolved drug to an in situ synthesized dicalcium phosphate (DCP)-PCL or solution-mixed beta-tricalcium phosphate (βTCP)-PCL composite powder followed by high pressure consolidation of the blend at room temperature. Vancomycin release was measured in phosphate-buffered saline (PBS) at 37°C. All the beads gradually released the drug over the period of 4-11weeks, depending on the composite matrix homogeneity and porosity. Mathematical modeling using the Peppas equation showed that vancomycin elution was diffusion controlled. The stability of the antibiotic after high pressure application at room temperature was demonstrated by high-performance liquid chromatography-mass spectrometry (HPLC-MS) studies and MIC testing. The preservation of the structure and activity of vancomycin during the processing of composite beads and its sustained in vitro release profile suggest that high pressure consolidated CaP-PCL beads may be useful in the treatment of chronic bone infections as resorbable delivery vehicles of vancomycin and even of thermally unstable drug substances.

  3. In-situ monitoring of drug release from therapeutic eluting polyelectrolyte multilayers under static and dynamic conditions

    NASA Astrophysics Data System (ADS)

    Tian, Fei; Min, Jouha; Kanka, Jiri; Hammond, Paula T.; Du, Henry

    2015-05-01

    The release profiles of gentamicin sulfate (GS) from [chitosan (CHI)/poly(acrylic acid) (PAA)/GS/PAA]n polyelectrolyte multilayers were investigated in situ using an innovative lab-on-fiber (LOF) optofluidic platform that mimics physiologically relevant fluid flow in a microenvironment. The LOF was constructed by enclosing in a flow-enabled and optically coupled glass capillary a long-period fiber grating both as a substrate for LbL growth of [CHI/PAA/GS/PAA]n and a measurement probe for GS release. We show that the LOF is very robust in monitoring the construction of the [CHI/PAA/GS/PAA]n multilayers at monolayer resolution as well as evaluating the rate of GS release with high sensitivity. The release processes in the LOF under static and a range of dynamic conditions are evaluated, showing a faster release under dynamic condition than that under static condition due to the varying circumstance of GS concentration gradient and the effect of flow-induced shear at the medium-multilayer interface. The LOF platform has the potential to be a powerful test bed to facilitate the design and evaluation of drug-eluting polyelectrolyte thin films for their clinical insertion as part of patient care strategy.

  4. Determination of sec-O-glucosylhamaudol in rat plasma by gradient elution liquid chromatography-mass spectrometry.

    PubMed

    Wen, Congcong; Lin, Chongliang; Cai, Xiaojun; Ma, Jianshe; Wang, Xianqin

    2014-01-01

    Sec-O-glucosylhamaudol is one of the major bioactive compounds of the Saposhnikoviae Radix. A simple and selective liquid chromatography-mass spectrometry (LC-MS) method for determination of sec-O-glucosylhamaudol in rat plasma was developed. After addition of carbamazepine as internal standard (IS), protein precipitation with acetonitrile-methanol (9:1, v/v) was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1mm×150mm, 5μm) column with acetonitrile-0.1% formic acid in water as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; selective ion monitoring (SIM) mode was used for quantification using target fragment ions m/z 439 for sec-O-glucosylhamaudol and m/z 237 for the IS. Calibration plots were linear over the range of 50-8000ng/mL for sec-O-glucosylhamaudol in rat plasma. Mean recovery of sec-O-glucosylhamaudol in plasma was in the range of 74.8-83.7%. Intra-day and inter-day precision were both <15%. This method was successfully applied in pharmacokinetic study after intravenous administration of 2.5mg/kg sec-O-glucosylhamaudol in rats.

  5. Waste on the roadside, 'poi-sute' waste: its distribution and elution potential of pollutants into environment.

    PubMed

    Moriwaki, Hiroshi; Kitajima, Shiori; Katahira, Kenshi

    2009-03-01

    Waste on the roadside, 'poi-sute' waste, was collected in a typical suburb in Japan (Ueda city, the sampling course: 3.2 km). The distribution, characterization of the 'poi-sute' waste and the loading of pollutants from the waste were studied. The average number of pieces of total waste was 690 pieces a month, and 220 pieces of waste were dumped a month per km. There was a tendency for much waste to be discarded around shops staying open until late at night. Regarding the sorts of the waste, cigarette butts are the most prevalent (the average was 150 cigarette butts/km/mo), and second was plastic materials. As for the weight, cigarette butts, plastics and papers were at a similar level (about 90 g/km/mo). The elution of arsenic (0.041 mg/L) and nicotine (3.8 mg/L) was ascertained by a dissolution test of 'poi-sute' cigarette butts obtained by sampling. Furthermore, the loading of heavy metals, such as lead, copper, chromium and cadmium, and polycyclic aromatic hydrocarbons (PAHs) from cigarette butts into the environment was confirmed. The load potentials of heavy metals were 0.020-1.7 mg/km/mo, and that of total-polyaromatic hydrocarbons was 0.032 mg/km/mo. These results indicate that the 'poi-sute' waste has a harmful influence on the environment.

  6. Protein adsorption on novel acrylamido-based polymeric ion-exchangers. III. Salt concentration effects and elution behavior.

    PubMed

    Hunter, A K; Carta, G

    2001-09-28

    The effect of salt concentration on the adsorption and desorption of BSA has been determined for a polymeric anion-exchanger based on acrylamido monomers. The material investigated possesses a high adsorption capacity at low salt concentration and the bound protein can be recovered quantitatively at high salt concentrations. The effects of salt on adsorption and desorption rates were evaluated from batch and shallow-bed experiments, and a model was developed to describe the data quantitatively. The adsorption capacity decreases as the salt concentration is increased, but both adsorption and desorption rates increase at higher salt concentrations. The predictability of the behavior of columns packed with this material was examined by comparing model predictions and experimental results obtained in laboratory columns. In general, a good agreement was obtained between predicted and experimental breakthrough and elution profiles, especially in shorter columns. Thus, the model allows a prediction of the effects of column length, mobile phase flow-rate, protein feed concentration, and salt concentration on dynamic capacity, productivity, and on the concentration of product fractions. PMID:11681582

  7. Utilities weather the storm

    SciTech Connect

    Lihach, N.

    1984-11-01

    Utilities must restore power to storm-damaged transmission and distribution systems, even if it means going out in ice storms or during lightning and hurricane conditions. Weather forecasting helps utilities plan for possible damage as well as alerting them to long-term trends. Storm planning includes having trained repair personnel available and adjusting the system so that less power imports are needed. Storm damage response requires teamwork and cooperation between utilities. Utilities can strengthen equipment in storm-prone or vulnerable areas, but good data are necessary to document the incidence of lighning strikes, hurricanes, etc. 2 references, 8 figures.

  8. Instructional Facility Utilization.

    ERIC Educational Resources Information Center

    Kalamazoo Valley Community Coll., MI.

    Data describing campus facility use for instructional and related purposes for one week of activity in Fall 1978 were collected and evaluated at Kalamazoo Valley Community College. Four measures of space utilization were used: (1) percent of available time used; (2) percent of available space used; (3) percent of scheduled space utilized; and (4)…

  9. Teuchos Utility Package

    2004-03-01

    Teuchos is designed to provide portable, object-oriented tools for Trillnos developers and users. This includes templated wrappers to BLAS/LAPACK, a serial dense matrix class, a parameter list, XML parsing utilities, reference counted pointer (smart pointer) utilities, and more. These tools are designed to run on both serial and parallel computers.

  10. Tribal water utility management

    SciTech Connect

    Not Available

    1993-03-01

    Contents: primacy program (what is primacy, advantages and disadvantages, treatment as a state, grant applications and funding); safe drinking water act (sampling requirements, coliform standard, public notification, surface water treatment rule impacts, uic and wellhead protection programs, lead/copper rule); water utility management (how is the utility program evaluated, who's responsible, what is the board and tribal council role).

  11. High-performance liquid chromatography of selenium compounds utilizing perfluorinated carboxylic acid ion-pairing agents and inductively coupled plasma and electrospray ionization mass spectrometric detection.

    PubMed

    Kotrebai, M; Tyson, J F; Block, E; Uden, P C

    2000-01-01

    Increasing speciation demands in clinical chemistry, toxicology and nutrition have made the determination of the total elements in a sample inadequate; the amount of an element and the chemical forms in which it is present need to be known. Inductively coupled plasma mass spectrometry (ICP-MS) was used after high-performance liquid chromatographic (HPLC) separation, as was electrospray ionization mass spectrometry (ESI-MS). The effect of variation of the number of carbon atoms in perfluorinated carboxylic acids used as ion-pairing agents for the separation of selenium compounds was examined. Trifluoroacetic acid (0.1%), pentafluoropropanoic acid (0.1%) or heptafluorobutanoic acid (0.1%; HFBA) were alternatively used as additives to methanol-water (1:99, v/v) solutions as mobile phases. Reversed-phase HPLC-ICP-MS with 0.1% HFBA in the mobile phase allowed more than 20 selenium compounds to be separated in 70 min in an isocratic elution mode; the separation of natural selenium-enriched sample extracts was examined and explained. The pH of the 0.1% HFBA solution was modified with hydrochloric acid or ammonia and the pH of the sample extracts before injection was modified in order to overcome unwanted double peak formation in the chromatograms of sample extracts. Oxidations of standard gamma-glutamyl-Se-methylselenocysteine and Se-methylselenocysteine were carried out using 30% H2O2 solution and identifications of selenium-containing oxidation products were made using HPLC-ICP-MS and HPLC-ESI-MS. The principal organic oxidation product in both cases was methaneseleninic acid (MeSeO2H).

  12. Successful treatment of recurrent carotid in-stent restenosis and drug-eluting balloon failure with a coronary bioresorbable vascular scaffold: A case report

    PubMed Central

    Giordano, Arturo; Ferraro, Paolo; Corcione, Nicola; Messina, Stefano; Maresca, Gennaro; Coscioni, Enrico; Biondi-Zoccai, Giuseppe

    2016-01-01

    Introduction Carotid in-stent restenosis is associated with substantial risk of recurrent restenosis, even after drug-eluting balloon usage. Presentation of case We hereby report the case of a patient with recurrent carotid in-stent restenosis and drug-eluting balloon failure treated with a coronary bioresorbable vascular scaffold, achieving a satisfactory acute and long-term result, as disclosed by duplex ultrasound scan performed more than 1 year after the procedure. Discussion/conclusion While awaiting for external validation, this clinical vignette supports expanding the armamentarium of endovascular specialists focusing on carotid artery disease, while providing further proof of the safety and efficacy of current bioresorbable vascular scaffolds. PMID:26945488

  13. Tamibarotene-loaded citric acid-crosslinked alkali-treated collagen matrix as a coating material for a drug-eluting stent

    NASA Astrophysics Data System (ADS)

    Inoue, Motoki; Takayanagi, Mariko; Fujiu, Katsuhito; Manabe, Ichiro; Nagai, Ryozo; Taguchi, Tetsushi

    2012-12-01

    Tamibarotene-loaded biodegradable matrices with antithrombogenic and drug-releasing properties were prepared in a crosslinking reaction between amino groups of alkali-treated collagen (AlCol) and active ester groups of trisuccinimidyl citrate. The resulting matrices were characterized by their residual amino group concentrations, swelling ratios and thermal, antithrombogenic and drug-releasing properties. It was clarified that the addition of tamibarotene does not inhibit matrix formation. After immersion in water, the swelling ratio of a matrix became lower than that prior to immersion. Thermal analysis indicated that AlCol interacted with tamibarotene. The addition of tamibarotene to the matrix did not influence the antithrombogenic property of the resulting matrix. A matrix with a high crosslinking density had a prolonged tamibarotene elution time. These results demonstrate that tamibarotene-loaded matrices have great potential as a coating material for drug-eluting stents.

  14. Fiscal year 1995 laboratory scale studies of Cs elution in Tank 8D-1 and sludge dissolution in tank 8D-2

    SciTech Connect

    Sills, J.A.; Patello, G.K.; Roberts, J.S.; Wiemers, K.D.; Elmore, M.R.; Richmond, W.G.; Russell, R.L.

    1996-04-01

    During Phase I of West Valley Demonstration project waste remediation, an estimated 95% of the zeolite currently in tank 8D-1 will be transferred to tank 8D-2, leaving behind residual Cs-loaded zeolite which will require treatment to remove the Cs. After phase I vitrification, tank 8D-2 will contain residual waste from PUREX and THOREX and spent Cs-loaded zeolite. The residual waste will require treatment. Oxalic acid has been proposed for eluting Cs from zeolite in tank 8D-1 and dissolving radionuclides in tank 8D-2. Laboratory tests were performed to determine optimum Cs elution and sludge dissolution conditions and to evaluate effects of multiple contacts, long-term contacts, presence of corrosion products, lack of agitation, temperature of tank contents, and oxalic acid concentration. Mild steel corrosion tests were also conducted.

  15. Advances in inline quantification of co-eluting proteins in chromatography: Process-data-based model calibration and application towards real-life separation issues.

    PubMed

    Brestrich, Nina; Sanden, Adrian; Kraft, Axel; McCann, Karl; Bertolini, Joseph; Hubbuch, Jürgen

    2015-07-01

    Pooling decisions in preparative liquid chromatography for protein purification are usually based on univariate UV absorption measurements that are not able to differentiate between product and co-eluting contaminants. This can result in inconsistent pool purities or yields, if there is a batch-to-batch variability of the feedstock. To overcome this analytical bottleneck, a tool for selective inline quantification of co-eluting model proteins using mid-UV absorption spectra and Partial Least Squares Regression (PLS) was presented in a previous study and applied for real-time pooling decisions. In this paper, a process-data-based method for the PLS model calibration will be introduced that allows the application of the tool towards chromatography steps of real-life processes. The process-data-based calibration method uses recorded inline mid-UV absorption spectra that are correlated with offline fraction analytics to calibrate PLS models. In order to generate average spectra from the inline data, a Visual Basic for Application macro was successfully developed. The process-data-based model calibration was established using a ternary model protein system. Afterwards, it was successfully demonstrated in two case studies that the calibration method is applicable towards real-life separation issues. The calibrated PLS models allowed a successful quantification of the co-eluting species in a cation-exchange-based aggregate and fraction removal during the purification of monoclonal antibodies and of co-eluting serum proteins in an anion-exchange-based purification of Cohn supernatant I. Consequently, the presented process-data-based PLS model calibration in combination with the tool for selective inline quantification has a great potential for the monitoring of future chromatography steps and may contribute to manage batch-to-batch variability by real-time pooling decisions. PMID:25683378

  16. Overlapping elution-extrusion counter-current chromatography: a novel method for efficient purification of natural cytotoxic andrographolides from Andrographis paniculata.

    PubMed

    Wu, Dingfang; Cao, Xiaoji; Wu, Shihua

    2012-02-01

    Counter-current chromatography (CCC) is extremely useful for the separation, purification, and isolation of natural products. Recently, Berthod et al. established an elution-extrusion CCC method in metabolic analysis by combining regular chromatographic elution with stationary-phase extrusion, which extends the hydrophobicity window of a counter-current separation. In this study, a novel overlapping elution-extrusion CCC method was developed and applied to the preparation of natural cytotoxic andrographolides from the aerial parts of Andrographis paniculata, a well-known Traditional Chinese Medicine (TCM) with potent anti-inflammatory effect and anti-cancer activity. Its theory was first developed, and then a series of CCC experiments were performed to investigate the efficiency of the method in the separation of the ethanol extracts from A. paniculata. Results show that overlapping elution-extrusion CCC is an efficient method to prepare a cytotoxic natural diterpenoid combination of 14-deoxy-andrographolide and 14-deoxy-11,12-didehydroandrographolide with the molar ratio of 1:2 as well as andrographolide using an optimized solvent system composed of hexane-ethyl acetate-ethanol-water (5:5:4:6, v/v) with an on-demand solvent preparation mode. All components obtained showed potent cytotoxic activity against human hepatocellular liver carcinoma cells HepG2 and doxorubicin-resistant R-HepG2 cells. Molecular structures have been identified by electrospray ionization mass spectrometry (ESI-MS), electrospray ionization time-of-flight mass spectrometry (ESI-TOF-MS), one- and two-dimensional nuclear magnetic resonance (1D- and 2D-NMR). The method appears to be very useful for the high-throughput purification of natural products.

  17. Advances in inline quantification of co-eluting proteins in chromatography: Process-data-based model calibration and application towards real-life separation issues.

    PubMed

    Brestrich, Nina; Sanden, Adrian; Kraft, Axel; McCann, Karl; Bertolini, Joseph; Hubbuch, Jürgen

    2015-07-01

    Pooling decisions in preparative liquid chromatography for protein purification are usually based on univariate UV absorption measurements that are not able to differentiate between product and co-eluting contaminants. This can result in inconsistent pool purities or yields, if there is a batch-to-batch variability of the feedstock. To overcome this analytical bottleneck, a tool for selective inline quantification of co-eluting model proteins using mid-UV absorption spectra and Partial Least Squares Regression (PLS) was presented in a previous study and applied for real-time pooling decisions. In this paper, a process-data-based method for the PLS model calibration will be introduced that allows the application of the tool towards chromatography steps of real-life processes. The process-data-based calibration method uses recorded inline mid-UV absorption spectra that are correlated with offline fraction analytics to calibrate PLS models. In order to generate average spectra from the inline data, a Visual Basic for Application macro was successfully developed. The process-data-based model calibration was established using a ternary model protein system. Afterwards, it was successfully demonstrated in two case studies that the calibration method is applicable towards real-life separation issues. The calibrated PLS models allowed a successful quantification of the co-eluting species in a cation-exchange-based aggregate and fraction removal during the purification of monoclonal antibodies and of co-eluting serum proteins in an anion-exchange-based purification of Cohn supernatant I. Consequently, the presented process-data-based PLS model calibration in combination with the tool for selective inline quantification has a great potential for the monitoring of future chromatography steps and may contribute to manage batch-to-batch variability by real-time pooling decisions.

  18. Percutaneous Transluminal Angioplasty and Drug-Eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI) Trial

    PubMed Central

    Spreen, Marlon I.; Martens, Jasper M.; Hansen, Bettina E.; Knippenberg, Bob; Verhey, Elke; van Dijk, Lukas C.; de Vries, Jean-Paul P.M.; Vos, Jan-Albert; de Borst, Gert Jan; Vonken, Evert-Jan P.A.; Wever, Jan J.; Statius van Eps, Randolph G.; Mali, Willem P.Th.M.

    2016-01-01

    Background— Endovascular infrapopliteal treatment of patients with critical limb ischemia using percutaneous transluminal angioplasty (PTA) and bail-out bare metal stenting (BMS) is hampered by restenosis. In interventional cardiology, drug-eluting stents (DES) have shown better patency rates and are standard practice nowadays. An investigator-initiated, multicenter, randomized trial was conducted to assess whether DES also improve patency and clinical outcome of infrapopliteal lesions. Methods and Results— Adults with critical limb ischemia (Rutherford category ≥4) and infrapopliteal lesions were randomized to receive PTA±BMS or DES with paclitaxel. Primary end point was 6-month primary binary patency of treated lesions, defined as ≤50% stenosis on computed tomographic angiography. Stenosis >50%, retreatment, major amputation, and critical limb ischemia–related death were regarded as treatment failure. Severity of failure was assessed with an ordinal score, ranging from vessel stenosis through occlusion to the clinical failures. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) received PTA±BMS. Six-month patency rates were 48.0% for DES and 35.1% for PTA±BMS (P=0.096) in the modified-intention-to-treat and 51.9% and 35.1% (P=0.037) in the per-protocol analysis. The ordinal score showed significantly worse treatment failure for PTA±BMS versus DES (P=0.041). The observed major amputation rate remained lower in the DES group until 2 years post-treatment, with a trend toward significance (P=0.066). Less minor amputations occurred after DES until 6 months post-treatment (P=0.03). Conclusions— In patients with critical limb ischemia caused by infrapopliteal lesions, DES provide better 6-month patency rates and less amputations after 6 and 12 months compared with PTA±BMS. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00471289. PMID:26861113

  19. Effects of interfacial layer wettability and thickness on the coating morphology and sirolimus release for drug-eluting stent.

    PubMed

    Bedair, Tarek M; Yu, Seung Jung; Im, Sung Gap; Park, Bang Ju; Joung, Yoon Ki; Han, Dong Keun

    2015-12-15

    Drug-eluting stents (DESs) have been used to treat coronary artery diseases by placing in the arteries. However, current DESs still suffer from polymer coating defects such as delamination and peeling-off that follows stent deployment. Such coating defects could increase the roughness of DES and might act as a source of late or very late thrombosis and might increase the incident of restenosis. In this regard, we modified the cobalt-chromium (Co-Cr) alloy surface with hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA) or hydrophobic poly(2-hydroxyethyl methacrylate)-grafted-poly(caprolactone) (PHEMA-g-PCL) brushes. The resulting surfaces were biocompatible and biodegradable, which could act as anchoring layer for the drug-in-polymer matrix coating. The two modifications were characterized by ATR-FTIR, XPS, water contact angle measurements, SEM and AFM. On the control and modified Co-Cr samples, a sirolimus (SRL)-containing poly(D,L-lactide) (PDLLA) were ultrasonically spray-coated, and the drug release was examined for 8weeks under physiological conditions. The results demonstrated that PHEMA as a primer coating improved the coating stability and degradation morphology, and drug release profile for short-term as compared to control Co-Cr, but fails after 7weeks in physiological buffer. On the other hand, the hydrophobic PHEMA-g-PCL brushes not only enhanced the stability and degradation morphology of the PDLLA coating layer, but also sustained SRL release for long-term. At 8-week of release test, the surface morphologies and release profiles of coated PDLLA layers verified the beneficial effect of hydrophobic PCL brushes as well as their thickness on coating stability. Our study concludes that 200nm thickness of PHEMA-g-PCL as interfacial layer affects the stability and degradation morphology of the biodegradable coating intensively to be applied for various biodegradable-based DESs. PMID:26319336

  20. Comparison of Bare Metal and Drug-Eluting Stents in Patients with Chronic Kidney Disease (From the NHLBI Dynamic Registry)

    PubMed Central

    Green, Sandy M.; Selzer, Faith; Mulukutla, Suresh R.; Tadajweski, Edward J.; Green, Jamie A.; Wilensky, Robert L.; Laskey, Warren K.; Cohen, Howard A.; Rao, Sunil V.; Weisbord, Steven D.; Lee, Joon S.; Reis, Steven E.; Kip, Kevin E.; Kelsey, Sheryl F.; Williams, David O.; Marroquin, Oscar C.

    2011-01-01

    Patients with chronic kidney disease (CKD) have a disproportionate burden of coronary artery disease and commonly undergo revascularization. The role and safety of percutaneous coronary intervention (PCI) using drug eluting stents (DES) verses bare metal stents (BMS) in CKD patients not on renal replacement therapy has not been fully evaluated. This study investigated the efficacy and safety of DES in patients with CKD not on renal replacement therapy. Patients where drawn from the National Heart, Lung, and Blood Institute Dynamic Registry and were stratified by renal function based on estimated glomerular filtration rate (GFR). Of the 4157 participants, 1108 had CKD (“low-GFR” <60 ml/min/1.73m2), while 3049 patients had normal renal function (“normal-GFR”≥60 ml/min/1.73m2). For each strata of renal function, we compared the risk of death, myocardial infarction (MI), or repeat revascularization between subjects who received DES and BMS at the index procedure. Patients with low-GFR had higher one-year rates of death and MI and a decreased rate of repeat revascularization when compared to patients with a normal-GFR. The use of DES was associated with a decreased need for repeat revascularization in the normal-GFR group (adjusted hazard ratio [HR] 0.63, 95% CI 0.50–0.79, p<0.001) but not in the low-GFR group (HR 0.69, 95% CI 0.45–1.06, p=0.09). The risks of death and MI were not different between the two stents in either patient population. In conclusion, the presence of CKD predicted poor outcomes after PCI with high rates of mortality regardless of stent type. The effect of DES in reducing repeat revascularization appeared to be attenuated in these patients. PMID:21890077

  1. Quantitative structure-retention relationships applied to development of liquid chromatography gradient-elution method for the separation of sartans.

    PubMed

    Golubović, Jelena; Protić, Ana; Otašević, Biljana; Zečević, Mira

    2016-04-01

    QSRR are mathematically derived relationships between the chromatographic parameters determined for a representative series of analytes in given separation systems and the molecular descriptors accounting for the structural differences among the investigated analytes. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. The aim of the present work was to optimize separation of six angiotensin receptor antagonists, so-called sartans: losartan, valsartan, irbesartan, telmisartan, candesartan cilexetil and eprosartan in a gradient-elution HPLC method. For this purpose, ANN as a mathematical tool was used for establishing a QSRR model based on molecular descriptors of sartans and varied instrumental conditions. The optimized model can be further used for prediction of an external congener of sartans and analysis of the influence of the analyte structure, represented through molecular descriptors, on retention behaviour. Molecular descriptors included in modelling were electrostatic, geometrical and quantum-chemical descriptors: connolly solvent excluded volume non-1,4 van der Waals energy, octanol/water distribution coefficient, polarizability, number of proton-donor sites and number of proton-acceptor sites. Varied instrumental conditions were gradient time, buffer pH and buffer molarity. High prediction ability of the optimized network enabled complete separation of the analytes within the run time of 15.5 min under following conditions: gradient time of 12.5 min, buffer pH of 3.95 and buffer molarity of 25 mM. Applied methodology showed the potential to predict retention behaviour of an external analyte with the properties within the training space. Connolly solvent excluded volume, polarizability and number of proton-acceptor sites appeared to be most influential paramateres on retention behaviour of the sartans.

  2. Efficient production of ethanol from waste paper and the biochemical methane potential of stillage eluted from ethanol fermentation.

    PubMed

    Nishimura, Hiroto; Tan, Li; Sun, Zhao-Yong; Tang, Yue-Qin; Kida, Kenji; Morimura, Shigeru

    2016-02-01

    Waste paper can serve as a feedstock for ethanol production due to being rich in cellulose and not requiring energy-intensive thermophysical pretreatment. In this study, an efficient process was developed to convert waste paper to ethanol. To accelerate enzymatic saccharification, pH of waste paper slurry was adjusted to 4.5-5.0 with H2SO4. Presaccharification and simultaneous saccharification and fermentation (PSSF) with enzyme loading of 40 FPU/g waste paper achieved an ethanol yield of 91.8% and productivity of 0.53g/(Lh) with an ethanol concentration of 32g/L. Fed-batch PSSF was used to decrease enzyme loading to 13 FPU/g waste paper by feeding two separate batches of waste paper slurry. Feeding with 20% w/w waste paper slurry increased ethanol concentration to 41.8g/L while ethanol yield decreased to 83.8%. To improve the ethanol yield, presaccharification was done prior to feeding and resulted in a higher ethanol concentration of 45.3g/L, a yield of 90.8%, and productivity of 0.54g/(Lh). Ethanol fermentation recovered 33.2% of the energy in waste paper as ethanol. The biochemical methane potential of the stillage eluted from ethanol fermentation was 270.5mL/g VTS and 73.0% of the energy in the stillage was recovered as methane. Integrating ethanol fermentation with methane fermentation, recovered a total of 80.4% of the energy in waste paper as ethanol and methane.

  3. Frequency of Vascular Inflammation and Impact on Neointimal Proliferation of Drug Eluting Stents in Porcine Coronary Arteries

    PubMed Central

    Yeh, Jong Shiuan; Oh, Seung Jin; Hsueh, Chun Mei

    2016-01-01

    Background We aimed to describe the frequency of vascular inflammatory reactions with second generation drug eluting stents (DES) compared to first generation DES, and analyze the impact on inflammation and neointimal proliferation in a porcine coronary model. Methods A total of 26 stents (7 multi-link VISION, 6 CYPHER, 6 TAXUS and 7 XIENCE V) were deployed in the coronary arteries of 10 domestic swine for 28 days, after which each stent was harvested and processed (divided into 8 or 9 segments) for histomorphometric analysis. Results A total of 202 histological segments [146 DES and 56 bare metal stents (BMS)] were included in this study. The mean neointimal thickness was significantly reduced in the DES group compared to the BMS group. The DES group had higher injury scores (DES = 0.99 ± 0.79 versus BMS = 0.67 ± 0.44, p < 0.004), inflammatory scores (DES = 2.09 ± 1.54 versus BMS = 0.64 ± 0.98, p < 0.001) and presence of para-strut granulomas (DES = 35% versus BMS = 2%, p < 0.001). In logistic regression analysis, the presence of para-strut granulomas correlated with an area of stenosis > 50% (RR: 6.11, 95% CI: 2.97 to 12.59, p = 0.001). In the DES group, the second generation stents had a lower neointimal area (XIENCE V: 1.64 ± 0.90 mm2) compared to the first generation stents (TAXUS: 2.36 ± 1.56 mm2, p = 0.005; CYPHER 2.78 ± 1.82 mm2, p = 0.001). The XIENCE V stents had lower inflammatory scores and lower frequency of para-strut granulomas compared to the first generation stents. Conclusions Second generation DES had a lower incidence of vascular inflammatory reactions compared to first generation DES. This biological phenomenon appears to influence the patterns of neointimal formation. PMID:27713606

  4. Pioglitazone Attenuates Drug-Eluting Stent-Induced Proinflammatory State in Patients by Blocking Ubiquitination of PPAR

    PubMed Central

    Wang, Zhongxia; Zhang, Tao; Sun, Lizhe; Li, Ruifeng; Wei, Yuanyuan; Yuan, Zuyi; Liu, Junhui; Chen, Tao

    2016-01-01

    The inflammatory response after polymer-based drug-eluting stent (DES) placement has recently emerged as a major concern. The biologic roles of peroxisome proliferator-activated receptor-γ (PPAR-γ) activators thiazolidinedione (TZD) remain controversial in cardiovascular disease. Herein, we investigated the antiinflammatory effects of pioglitazone (PIO) on circulating peripheral blood mononuclear cells (MNCs) in patients after coronary DES implantation. Methods and Results. Twenty-eight patients with coronary artery disease and who underwent DES implantations were randomly assigned to pioglitazone (30 mg/d; PIO) or placebo (control; Con) treatment in addition to optimal standard therapy. After 12 weeks of treatment, plasma concentrations of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-9 (MMP-9) were significantly decreased in PIO group compared to the Con group (P = 0.035, 0.011, 0.008, and 0.012, resp.). DES-induced mRNA expressions of IL-6, TNF-α, and MMP-9 in circulating MNC were significantly blocked by PIO (P = 0.031, 0.012, and 0.007, resp.). In addition, PIO markedly inhibited DES-enhanced NF-κB function and DES-blocked PPAR-γ activity. Mechanically, DES induced PPAR-γ ubiquitination and degradation in protein level, which can be totally reversed by PIO. Conclusion. PIO treatment attenuated DES-induced PPAR loss, NF-κB activation, and proinflammation, indicating that PIO may have a novel direct protective role in modulating proinflammation in DES era. PMID:27403152

  5. Prospective Randomized Comparison of Chemoembolization with Doxorubicin-Eluting Beads and Bland Embolization with BeadBlock for Hepatocellular Carcinoma

    SciTech Connect

    Malagari, Katerina; Pomoni, Mary; Kelekis, Alexis; Pomoni, Anastasia; Dourakis, Spyros; Spyridopoulos, Themis; Moschouris, Hippokratis; Emmanouil, Emmanouil; Rizos, Spyros; Kelekis, Dimitrios

    2010-06-15

    The purpose of this study was to evaluate the added role of a chemotherapeutic in transarterial chemoembolization (TACE) of intermediate-stage hepatocellular carcinoma (HCC). The issue is of major importance since, as suggested by recent evidence, hypoxia or incomplete devascularization of the tumor is a potent stimulator of angiogenesis, and there are not many papers supplying level one evidence confirming the value of a chemotherapeutic. The hypothesis was that since drug-eluting bead (DEB)-TACE is standardized and reproducible, a comparison with bland TACE can readily reveal the potential value of the chemotherapeutic. Two groups were randomized in this prospective study: group A (n = 41) was treated with doxorubicin DEB-TACE, and group B (n = 43) with bland embolization. Patients were randomized for tumor diameter. Patients were embolized at set time intervals (2 months), with a maximum of three embolizations. Tumor response was evaluated using the EASL criteria and {alpha}-fetoprotein levels. At 6 months a complete response was seen in 11 patients (26.8%) in the DEB-TACE group and in 6 patients (14%) in the bland embolization group; a partial response was achieved in 19 patients (46.3%) and 18 (41.9%) patients in the DEB-TACE and bland embolization groups, respectively. Recurrences at 9 and 12 months were higher for bland embolization (78.3% vs. 45.7%) at 12 months. Time to progression (TTP) was longer for the DEB-TACE group (42.4 {+-} 9.5 and 36.2 {+-} 9.0 weeks), at a statistically significant level (p = 0.008). In conclusion, DEB-TACE presents a better local response, fewer recurrences, and a longer TTP than bland embolization with BeadBlock. However, survival benefit and bland embolization with smaller particles must be addressed in future papers to better assess the clinical value.

  6. First- Versus Second-Generation Drug-Eluting Stents in Acute Coronary Syndromes (Katowice-Zabrze Registry)

    PubMed Central

    Kawecki, Damian; Morawiec, Beata; Dola, Janusz; Waha, Wojciech; Smolka, Grzegorz; Pluta, Aleksandra; Marcinkiewicz, Kamil; Ochała, Andrzej; Nowalany-Kozielska, Ewa; Wojakowski, Wojciech

    2016-01-01

    Background There are sparse data on the performance of different types of drug-eluting stents (DES) in acute and real-life setting. Objective The aim of the study was to compare the safety and efficacy of first- versus second-generation DES in patients with acute coronary syndromes (ACS). Methods This all-comer registry enrolled consecutive patients diagnosed with ACS and treated with percutaneous coronary intervention with the implantation of first- or second-generation DES in one-year follow-up. The primary efficacy endpoint was defined as major adverse cardiac and cerebrovascular event (MACCE), a composite of all-cause death, nonfatal myocardial infarction, target-vessel revascularization and stroke. The primary safety outcome was definite stent thrombosis (ST) at one year. Results From the total of 1916 patients enrolled into the registry, 1328 patients were diagnosed with ACS. Of them, 426 were treated with first- and 902 with second-generation DES. There was no significant difference in the incidence of MACCE between two types of DES at one year. The rate of acute and subacute ST was higher in first- vs. second-generation DES (1.6% vs. 0.1%, p < 0.001, and 1.2% vs. 0.2%, p = 0.025, respectively), but there was no difference regarding late ST (0.7% vs. 0.2%, respectively, p = 0.18) and gastrointestinal bleeding (2.1% vs. 1.1%, p = 0.21). In Cox regression, first-generation DES was an independent predictor for cumulative ST (HR 3.29 [1.30-8.31], p = 0.01). Conclusions In an all-comer registry of ACS, the one-year rate of MACCE was comparable in groups treated with first- and second-generation DES. The use of first-generation DES was associated with higher rates of acute and subacute ST and was an independent predictor of cumulative ST. PMID:27058257

  7. Unenhanced and Contrast-Enhanced Ultrasonography During Hepatic Transarterial Embolization and Chemoembolization With Drug-Eluting Beads

    SciTech Connect

    Moschouris, Hippocrates; Malagari, Katerina; Kornezos, Ioannis; Papadaki, Marina Georgiou; Gkoutzios, Panagiotis; Matsaidonis, Dimitrios

    2010-12-15

    The purpose of this study was to describe and evaluate the findings of unenhanced ultrasonography (US) and contrast-enhanced ultrasonography (CEUS) when these modalities are applied during transarterial embolization (TAE) or transarterial chemoembolization (TACE) of liver tumors. Sixteen tumors (9 hepatocellular carcinomas, 5 metastases from colorectal cancer, and 2 hemangiomas) were treated with TAE with microspheres and/or TACE with drug-eluting beads. All of these lesions were studied with intraprocedural unenhanced US and 12 were studied with intraprocedural CEUS. For the latter, a second-generation echo-enhancer (SonoVue; Bracco, Milan, Italy) and a low mechanical index technique were used. Intraprocedural findings were classified according to an arbitrary scale and were compared with pretreatment imaging (CEUS and computed tomography or CEUS and magnetic resonance imaging), with postembolization angiography, and with follow-up results. On unenhanced intraprocedural US, 13 of 16 tumors demonstrated intralesional high-level echoes of varying extent. These feature correlated poorly (r = 0.33, p = 0.097) with and generally underestimated the actual extent of necrosis. Exceptionally, high-level echoes that occupied the largest part of the treated lesions were associated with >50% tumor necrosis. Intraprocedural CEUS clearly depicted immediate partial or complete disappearance of tumor enhancement as a result of TAE/TACE. Three of 6 tumors with complete devascularization on postembolization angiogram showed residual enhancement on intraprocedural CEUS. Intraprocedural CEUS findings correlated closely (r = 0.91, p = 0.002) with follow-up findings. Intraprocedural sonography, particularly with echo-enhancers, could be used for intraprocedural monitoring in selected cases of liver tumors that undergo TAE or TACE.

  8. Association of Localized Hypersensitivity and In-Stent Neoatherosclerosis with the Very Late Drug-Eluting Stent Thrombosis

    PubMed Central

    Yamaji, Kyohei; Kubo, Shunsuke; Inoue, Katsumi; Kadota, Kazushige; Kuramitsu, Shoichi; Shirai, Shinichi; Ando, Kenji; Nobuyoshi, Masakiyo; Mitsudo, Kazuaki; Kimura, Takeshi

    2014-01-01

    Background Localized hypersensitivity reaction, delayed arterial healing, and neoatherosclerosis inside the stent have been suggested as the underlying pathologic mechanisms of very late stent thrombosis (VLST) of drug-eluting stent (DES). The present study sought to explore the prevalence of inflammatory cell infiltrates and evidence for fragments of atherosclerotic plaques in the aspirated thrombi in patients with DES VLST. Methods and Results From April 2004 to September 2012, 48 patients with stent thrombosis (ST) of DES underwent thrombus aspiration with retrieved material sufficient for the histopathologic analysis; early ST (EST, within 30 days): N = 17, late ST (LST, between 31 and 365 days): N = 7, and very late ST (VLST, >1 year): N = 24. Eosinophil fraction in the aspirated thrombi was significantly higher in patients with VLST (8.2±5.7%) as compared with those with EST (4.3±3.0%) and LST (5.5±3.8%) (P = 0.03). Eosinophil fraction in the aspirated thrombi was significantly higher in 12 VLST patients with angiographic peri-stent contrast staining (PSS) and/or incomplete stent apposition (ISA) by intravascular ultrasound than in 12 VLST patients without PSS or ISA (10.6±6.1% versus 5.8±4.1%, P = 0.03). Evidences for fragments of atherosclerotic plaques in the aspirated thrombi were observed only in 3 (13%) out of 24 patients with DES VLST. Conclusions Eosinophil fraction in the aspirated thrombi was significantly higher in patients with DES VLST as compared with those with EST and LST. Evidences for fragments of atherosclerotic plaques were relatively uncommon in patients with DES VLST. PMID:25423451

  9. Long-term clinical outcomes of drug-eluting stents vs. bare-metal stents in Chinese geriatric patients

    PubMed Central

    Chan, Pak-Hei; Liu, Sha-Sha; Tse, Hung-Fat; Chow, Wing-Hing; Jim, Man-Hong; HO, Hee-Hwa; Siu, Chung Wah

    2013-01-01

    Background & objective Little is known about the relative efficacies of percutaneous coronary intervention (PCI) with drug-eluting stents (DES) and bare-metal stents (BMS) in elderly patients. The objective of this study was to evaluate the clinical outcome for geriatric patients who received either DES or BMS. Methods From January 2002 to October 2005, 199 consecutive Chinese geriatric patients (≥ 75 years old) underwent PCI with coronary DES or BMS implantation at our institution. We analyzed the major clinical end points that included all-cause mortality, cardiovascular death, myocardial infarction, target lesion revascularization (TLR), stent thrombosis, and bleeding complications. Results The three-year cumulative rates of all-cause mortality, cardiovascular death, and myocardial infarction were significantly lower in the DES group (6.3%, 3.6%, 5.4%) compared with the BMS group (16.2%, 11.5%, 14.9%; P < 0.05). No significant differences were found in the three-year cumulative rate for target lesion revascularization (6.3% vs. 4.6%, P = 0.61) or stent thrombosis (3.6% vs. 2.3%, P = 0.70). Likewise, there were no statistically significant differences in the cumulative rate for intracranial hemorrhage, or major and minor hemorrhage at three years. Conclusions DES-based PCI was associated with a significant reduction in the three-year cumulative rate of all-cause mortality, cardiovascular death, and myocardial infarction compared with BMS, without increased risk of TLR, stent thrombosis, or bleeding complications at three years in this group of Chinese geriatric patients. PMID:24454325

  10. Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention

    PubMed Central

    Baschet, Louise; Bourguignon, Sandrine; Marque, Sébastien; Durand-Zaleski, Isabelle; Teiger, Emmanuel; Wilquin, Fanny; Levesque, Karine

    2016-01-01

    Objective To determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES. Methods A cost-effectiveness analysis was performed in the French National Health Insurance setting. Effectiveness settings were taken from a meta-analysis of 117 762 patient-years with 76 randomised trials. The main effectiveness criterion was major cardiac event-free survival. Effectiveness and costs were modelled over a 5-year horizon using a three-state Markov model. Incremental cost-effectiveness ratios and a cost-effectiveness acceptability curve were calculated for a range of thresholds for willingness to pay per year without major cardiac event gain. Deterministic and probabilistic sensitivity analyses were performed. Results Base case results demonstrated that DES are dominant over BMS, with an increase in event-free survival and a cost-reduction of €184, primarily due to a diminution of second revascularisations, and an absence of myocardial infarction and stent thrombosis. These results are robust for uncertainty on one-way deterministic and probabilistic sensitivity analyses. Using a cost-effectiveness threshold of €7000 per major cardiac event-free year gained, DES has a >95% probability of being cost-effective versus BMS. Conclusions Following DES price decrease, new-generation DES development and taking into account recent meta-analyses results, the DES can now be considered cost-effective regardless of selective indication in France, according to European recommendations.

  11. Numerical simulation on the effects of drug eluting stents at different Reynolds numbers on hemodynamic and drug concentration distribution

    PubMed Central

    2015-01-01

    Background The changes of hemodynamics and drug concentration distribution caused by the implantation of drug eluting stents (DESs) in curved vessels have significant effects on In-Stent Restenosis. Methods A 3D virtual stent with 90°curvature was modelled and the distribution of wall shear stress (WSS) and drug concentration in this model were numerically studied at Reynolds numbers of 200, 400, 600, 800. Results The results showed that (1) the intensity of secondary flow at the 45° cross-section was stronger than that at the 90° cross-section; (2) As the Reynolds number increases, the WSS decreases. When the Reynolds number reaches 600, the low-WSS region only accounts for 3% of the total area. (3) The effects of Reynolds number on drug concentration in the vascular wall decreases in proportionally and then the blood velocity increased 4 times, the drug concentration in the vascular wall decreased by about 30%. (4) The size of the high drug concentration region is inversely proportional to the Reynolds number. As the blood velocity increases, the drug concentration in the DES decreases, especially at the outer bend. Conclusions It is beneficial for the patient to decrease vigorous activities and keep calm at the beginning of the stent implantation, because a substantial amount of the drug is released in the first two months of stent implantation, thus a calm status is conducive to drug release and absorption; Subsequently, appropriate exercise which increases the blood velocity is helpful in decreasing regions of low-WSS. PMID:25602685

  12. Cost-effectiveness of drug-eluting stents versus bare-metal stents in patients undergoing percutaneous coronary intervention

    PubMed Central

    Baschet, Louise; Bourguignon, Sandrine; Marque, Sébastien; Durand-Zaleski, Isabelle; Teiger, Emmanuel; Wilquin, Fanny; Levesque, Karine

    2016-01-01

    Objective To determine the cost-effectiveness of drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients requiring a percutaneous coronary intervention in France, using a recent meta-analysis including second-generation DES. Methods A cost-effectiveness analysis was performed in the French National Health Insurance setting. Effectiveness settings were taken from a meta-analysis of 117 762 patient-years with 76 randomised trials. The main effectiveness criterion was major cardiac event-free survival. Effectiveness and costs were modelled over a 5-year horizon using a three-state Markov model. Incremental cost-effectiveness ratios and a cost-effectiveness acceptability curve were calculated for a range of thresholds for willingness to pay per year without major cardiac event gain. Deterministic and probabilistic sensitivity analyses were performed. Results Base case results demonstrated that DES are dominant over BMS, with an increase in event-free survival and a cost-reduction of €184, primarily due to a diminution of second revascularisations, and an absence of myocardial infarction and stent thrombosis. These results are robust for uncertainty on one-way deterministic and probabilistic sensitivity analyses. Using a cost-effectiveness threshold of €7000 per major cardiac event-free year gained, DES has a >95% probability of being cost-effective versus BMS. Conclusions Following DES price decrease, new-generation DES development and taking into account recent meta-analyses results, the DES can now be considered cost-effective regardless of selective indication in France, according to European recommendations. PMID:27621830

  13. Stent thrombosis in real-world patients: a comparison of drug-eluting with bare metal stents

    PubMed Central

    de Man, F.H.; Stella, P.R.; Nathoe, H.; Kirkels, H.; Hamer, B.; Meijburg, H.W.; Doevendans, P.A.

    2007-01-01

    Background Although the introduction of drugeluting stents (DES) has been associated with an impressive reduction in target vessel revascularisation, there has been concern about the safety profile. The aim of this study was to determine the incidence of stent thrombosis in real-world patients and evaluate the contribution of drug-eluting stents. Methods A prospective observational cohort study was conducted at a high-volume centre in Utrecht, the Netherlands. All patients who underwent a percutaneous coronary intervention (PCI) between 1 January and 31 December 2005 were evaluated. The patients were pretreated with aspirin and clopidogrel, which was continued for six months in bare metal stents (BMS) and 12 months in DES. Results In 2005, 1309 patients underwent a percutaneous coronary intervention procedure with stent implantation. After a median follow-up of nine months, 1.8% (n=23) of the patients had suffered from stent thrombosis. Two cases could be attributed to incorrect use of antiplatelet agents. In 8/23 cases, a technical reason was found such as an unrecognised dissection or stent underexpansion. The timing of stent thrombosis was acute in 1/23 patients, subacute in 20/23 patients and late in 2/23 patients. In both cases of late stent thrombosis, a BMS had been used. There were no differences in stent thrombosis rates between DES and BMS (1.4 vs. 1.9%, ns.). This is remarkable since DES were used in more complex and longer lesions. Conclusion The use of DES in routine daily practice does not appear to be associated with a higher rate of stent thrombosis than BMS. (Neth Heart J 2007;15:382-6.18176640Neth Heart J 2007;15:382-6). PMID:18176640

  14. Impact of stent length on clinical outcomes of first-generation and new-generation drug-eluting stents.

    PubMed

    Konishi, Hirokazu; Miyauchi, Katsumi; Dohi, Tomotaka; Tsuboi, Shuta; Ogita, Manabu; Naito, Ryo; Kasai, Takatoshi; Tamura, Hiroshi; Okazaki, Shinya; Isoda, Kikuo; Daida, Hiroyuki

    2016-04-01

    The aim of this study is to compare first- and new-generation drug-eluting stents (DESs) which are implanted in long lesion. Stent length is known to be a predictor of adverse events after percutaneous coronary intervention (PCI), even with the first-generation DESs. The introduction of new-generation DESs has reduced the rates of adverse clinical events. However, the impact of stent length on long-term clinical outcomes is not well known. A total of 1181 consecutive patients who underwent PCI using either a first-generation DES (n = 885) or a new-generation DES (n = 296) between 2004 and 2011 were investigated. In each of the stent groups, the patients were divided into two groups by stent length (>32 and ≤32 mm) and compared. During the follow-up period, the incidence of major adverse cardiac events (MACEs) was significantly higher for patients with long stents implanted than with short stents (P < 0.01; log-rank test) in the first-generation DES group. However, there was no difference in the incidence of MACEs between the long- and short-stent groups in the new-generation DES group (P = 0.24; log-rank test). On multivariate Cox regression analysis, stent length was not associated with adverse events in the new-generation DES groups [hazard ratio (HR) 0.87; 95 % confidence interval (95 % CI) 0.71-1.04; P = 0.14]. Implanted stent length was significantly associated with a higher risk of MACEs in patients who received first-generation DESs, but not in patients who received the new-generation DESs.

  15. Improving smooth muscle cell exposure to drugs from drug-eluting stents at early time points: a variable compression approach.

    PubMed

    O'Connell, Barry M; Cunnane, Eoghan M; Denny, William J; Carroll, Grainne T; Walsh, Michael T

    2014-08-01

    The emergence of drug-eluting stents (DES) as a viable replacement for bare metal stenting has led to a significant decrease in the incidence of clinical restenosis. This is due to the transport of anti-restenotic drugs from within the polymer coating of a DES into the artery wall which arrests the cell cycle before restenosis can occur. The efficacy of DES is still under close scrutiny in the medical field as many issues regarding the effectiveness of DES drug transport in vivo still exist. One such issue, that has received less attention, is the limiting effect that stent strut compression has on the transport of drug species in the artery wall. Once the artery wall is compressed, the stents ability to transfer drug species into the arterial wall can be reduced. This leads to a reduction in the spatial therapeutic transfer of drug species to binding sites within the arterial wall. This paper investigates the concept of idealised variable compression as a means of demonstrating how such a stent design approach could improve the spatial delivery of drug species in the arterial wall. The study focused on assessing how the trends in concentration levels changed as a result of artery wall compression. Five idealised stent designs were created with a combination of thick struts that provide the necessary compression to restore luminal patency and thin uncompressive struts that improve the transport of drugs therein. By conducting numerical simulations of diffusive mass transport, this study found that the use of uncompressive struts results in a more uniform spatial distribution of drug species in the arterial wall.

  16. Effects of interfacial layer wettability and thickness on the coating morphology and sirolimus release for drug-eluting stent.

    PubMed

    Bedair, Tarek M; Yu, Seung Jung; Im, Sung Gap; Park, Bang Ju; Joung, Yoon Ki; Han, Dong Keun

    2015-12-15

    Drug-eluting stents (DESs) have been used to treat coronary artery diseases by placing in the arteries. However, current DESs still suffer from polymer coating defects such as delamination and peeling-off that follows stent deployment. Such coating defects could increase the roughness of DES and might act as a source of late or very late thrombosis and might increase the incident of restenosis. In this regard, we modified the cobalt-chromium (Co-Cr) alloy surface with hydrophilic poly(2-hydroxyethyl methacrylate) (PHEMA) or hydrophobic poly(2-hydroxyethyl methacrylate)-grafted-poly(caprolactone) (PHEMA-g-PCL) brushes. The resulting surfaces were biocompatible and biodegradable, which could act as anchoring layer for the drug-in-polymer matrix coating. The two modifications were characterized by ATR-FTIR, XPS, water contact angle measurements, SEM and AFM. On the control and modified Co-Cr samples, a sirolimus (SRL)-containing poly(D,L-lactide) (PDLLA) were ultrasonically spray-coated, and the drug release was examined for 8weeks under physiological conditions. The results demonstrated that PHEMA as a primer coating improved the coating stability and degradation morphology, and drug release profile for short-term as compared to control Co-Cr, but fails after 7weeks in physiological buffer. On the other hand, the hydrophobic PHEMA-g-PCL brushes not only enhanced the stability and degradation morphology of the PDLLA coating layer, but also sustained SRL release for long-term. At 8-week of release test, the surface morphologies and release profiles of coated PDLLA layers verified the beneficial effect of hydrophobic PCL brushes as well as their thickness on coating stability. Our study concludes that 200nm thickness of PHEMA-g-PCL as interfacial layer affects the stability and degradation morphology of the biodegradable coating intensively to be applied for various biodegradable-based DESs.

  17. A tool for selective inline quantification of co-eluting proteins in chromatography using spectral analysis and partial least squares regression.

    PubMed

    Brestrich, Nina; Briskot, Till; Osberghaus, Anna; Hubbuch, Jürgen

    2014-07-01

    Selective quantification of co-eluting proteins in chromatography is usually performed by offline analytics. This is time-consuming and can lead to late detection of irregularities in chromatography processes. To overcome this analytical bottleneck, a methodology for selective protein quantification in multicomponent mixtures by means of spectral data and partial least squares regression was presented in two previous studies. In this paper, a powerful integration of software and chromatography hardware will be introduced that enables the applicability of this methodology for a selective inline quantification of co-eluting proteins in chromatography. A specific setup consisting of a conventional liquid chromatography system, a diode array detector, and a software interface to Matlab® was developed. The established tool for selective inline quantification was successfully applied for a peak deconvolution of a co-eluting ternary protein mixture consisting of lysozyme, ribonuclease A, and cytochrome c on SP Sepharose FF. Compared to common offline analytics based on collected fractions, no loss of information regarding the retention volumes and peak flanks was observed. A comparison between the mass balances of both analytical methods showed, that the inline quantification tool can be applied for a rapid determination of pool yields. Finally, the achieved inline peak deconvolution was successfully applied to make product purity-based real-time pooling decisions. This makes the established tool for selective inline quantification a valuable approach for inline monitoring and control of chromatographic purification steps and just in time reaction on process irregularities.

  18. Elution profiles of tobramycin and vancomycin from high-purity calcium sulphate beads incubated in a range of simulated body fluids.

    PubMed

    Cooper, J J; Florance, H; McKinnon, J L; Laycock, P A; Aiken, S S

    2016-09-01

    The aim of this study was to characterise the elution profiles of antibiotics in combination with pharmaceutical grade calcium sulphate beads in phosphate buffered saline and other physiological solutions which more closely mimic the in vivo environment. Synthetic recrystallised calcium sulphate was combined with vancomycin hydrochloride powder and tobramycin sulphate solution and the paste was formed into 3 mm diameter hemispherical beads. Then 2 g of beads were immersed in 2 ml of either phosphate buffered saline, Dulbecco's Modified Eagle Medium or Hartmann's solution and incubated at 37℃ for up to 21 days. At a range of time points, eluent was removed for analysis by liquid chromatography-mass spectrometry (LC-MS). Tobramycin sulphate and vancomycin hydrochloride release was successfully quantified against standard curves from solutions eluted in all three physiological media (phosphate buffered saline, Dulbecco's Modified Eagle Medium and Hartmann's solution) during incubation with calcium sulphate beads. One hour eluate concentrations were high, up to 2602 µg/ml for tobramycin in phosphate buffered saline and 7417 µg/ml for vancomycin, whereas in DMEM, the levels of tobramycin were 2458 µg/ml and 4401 µg/ml for vancomycin. The levels in HRT were 2354 µg/ml for tobramycin and 5948 µg/ml for vancomycin. The results show highest levels of antibiotic elution over the first 24 h, which gradually diminish over the following 21 days. PMID:27511982

  19. Concentration- and roughness-dependent antibacterial and antifungal activities of CuO thin films and their Cu ion cytotoxicity and elution behavior.

    PubMed

    Shim, Gyu-In; Kim, Seong-Hwan; Eom, Hyung-Woo; Choi, Se-Young

    2015-05-01

    In this study, we aimed to evaluate the antibacterial and antifungal properties, cytotoxicity, and elution behavior of copper oxide (CuO) thin films with varying concentrations and roughness values. CuO films greater than 0.2 mol % showed 99.9 % antimicrobial activity against Escherichia coli, Staphylococcus aureus, Campylobacter jejuni, and Penicillium funiculosum. Cu ions were found to be noncytotoxic in New Zealand white rabbits. The concentration of Cu ions from CuO thin films eluted in drinking water in 24 h at 100 °C was 0.014 μg L(-1), which was below the standard acceptable level of 0.02 μg L(-1). The transmittance of CuO thin film-coated glass was similar to that of parent glass. The antimicrobial activity, cytotoxicity, elution behavior, and transmittance of CuO deposited on glass suggest that these films could be useful in household devices and display devices.

  20. PAM stack test utility

    2007-08-22

    The pamtest utility calls the normal PAM hooks using a service and username supplied on the command line. This allows an administratory to test any one of many configured PAM stacks as any existing user on the machine.

  1. Understanding the Utilities.

    ERIC Educational Resources Information Center

    Matthews, Joseph R.

    1980-01-01

    Briefly describes the origin and development of some major online bibliographic utilities, including the Ohio College Library Center (OCLC), the Research Libraries Information Network (RLIN), the University of Toronto Library Automation Systems (UTLAS), and the Washington Library Network (WLN). (FM)

  2. Nine-Months Clinical Outcome of Biodegradable Polymer Coated Sirolimus-eluting Stent System: A Multi-Centre “Real-World” Experience

    PubMed Central

    Prajapati, Jayesh; Raheem, Asif; Thakkar, Kamlesh; Kothari, Shivani; Thakkar, Ashok

    2015-01-01

    Background The main culprit in first-generation drug eluting stents is ‘durable’ polymer, whose continuous presence may impair arterial healing and ultimately have a negative impact on late outcomes. The main enigma behind the biodegradable polymer usage is its degradation after elution of drug. This reduces adverse events in unselected patients with complex coronary artery lesions treated with biodegradable polymer coated sirolimus-eluting stents. Aim The aim of the INDOLIMUS-G Registry was to evaluate safety and efficacy of the Indolimus (Sahajanand Medical Technologies Pvt. Ltd., Surat, India) sirolimus-eluting stents in large cohorts of unselected patients with complex coronary artery lesions. Materials and Methods It is a multi-centre, non-randomized retrospective registry with a clear aim of evaluating safety and efficacy of the Indolimus sirolimus-eluting stents in consecutive patients enrolled between April 2012 and May 2014. The primary end-point of the study was major adverse cardiac events (MACE), which is a composite of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR) and stent thrombosis (ST) at the end of follow-up. Clinical follow-up were scheduled at the end of 30-days, 6-months, and 9-months period. Results The mean age of enrolled patients was 52.6 ± 11.0 years. A total of 1137 lesions were intervened successfully with 1242 stents (1.09 ± 0.30 stent per lesion). The average stent length and diameter was 27.42 ± 9.01 mm and 3.12 ± 0.36 mm respectively. There were 740 (73.40%) male patients, indicating their high prevalence. Diabetes, hypertension and totally occluded lesions were found in 372 (36.90%), 408 (40.47%) and 170 (16.86%) patients, respectively. This showed that study also included high risk complex lesions and not ideal recruited lesions. The incidence of MACE at 30-days, 6-months and 9-months were 3 (0.30%), 18 (1.80%) and 22 (2.20%) respectively. At 9-months

  3. Mechanisms and Patterns of Intravascular Ultrasound In-Stent Restenosis Among Bare Metal Stents and First- and Second-Generation Drug-Eluting Stents.

    PubMed

    Goto, Kosaku; Zhao, Zhijing; Matsumura, Mitsuaki; Dohi, Tomotaka; Kobayashi, Nobuaki; Kirtane, Ajay J; Rabbani, LeRoy E; Collins, Michael B; Parikh, Manish A; Kodali, Susheel K; Leon, Martin B; Moses, Jeffrey W; Mintz, Gary S; Maehara, Akiko

    2015-11-01

    The most common causes of in-stent restenosis (ISR) are intimal hyperplasia and stent under expansion. The purpose of this study was to use intravascular ultrasound (IVUS) to compare the ISR mechanisms of bare metal stents (BMS), first-generation drug-eluting stents (DES), and second-generation DES. There were 298 ISR lesions including 52 BMS, 73 sirolimus-eluting stents, 52 paclitaxel-eluting stents, 16 zotarolimus-eluting stents, and 105 everolimus-eluting stent. Mean patient age was 66.6 ± 1.1 years, 74.2% were men, and 48.3% had diabetes mellitus. BMS restenosis presented later (70.0 ± 66.7 months) with more intimal hyperplasia compared with DES (BMS 58.6 ± 15.5%, first-generation DES 52.6 ± 20.9%, second-generation DES 48.2 ± 22.2%, p = 0.02). Although reference lumen areas were similar in BMS and first- and second-generation DES, restenotic DES were longer (BMS 21.8 ± 13.5 mm, first-generation DES 29.4 ± 16.1 mm, second-generation DES 32.1 ± 18.7 mm, p = 0.003), and stent areas were smaller (BMS 7.2 ± 2.4 mm(2), first-generation DES 6.1 ± 2.1 mm(2), second-generation DES 5.7 ± 2.0 mm(2), p <0.001). Stent fracture was seen only in DES (first-generation DES 7 [5.0%], second-generation DES 8 [7.4%], p = 0.13). In conclusion, restenotic first- and second-generation DES were characterized by less neointimal hyperplasia, smaller stent areas, longer stent lengths, and more stent fractures than restenotic BMS.

  4. Measuring Resource Utilization

    PubMed Central

    Leggett, Laura E.; Khadaroo, Rachel G.; Holroyd-Leduc, Jayna; Lorenzetti, Diane L.; Hanson, Heather; Wagg, Adrian; Padwal, Raj; Clement, Fiona

    2016-01-01

    Abstract A variety of methods may be used to obtain costing data. Although administrative data are most commonly used, the data available in these datasets are often limited. An alternative method of obtaining costing is through self-reported questionnaires. Currently, there are no systematic reviews that summarize self-reported resource utilization instruments from the published literature. The aim of the study was to identify validated self-report healthcare resource use instruments and to map their attributes. A systematic review was conducted. The search identified articles using terms like “healthcare utilization” and “questionnaire.” All abstracts and full texts were considered in duplicate. For inclusion, studies had to assess the validity of a self-reported resource use questionnaire, to report original data, include adult populations, and the questionnaire had to be publically available. Data such as type of resource utilization assessed by each questionnaire, and validation findings were extracted from each study. In all, 2343 unique citations were retrieved; 2297 were excluded during abstract review. Forty-six studies were reviewed in full text, and 15 studies were included in this systematic review. Six assessed resource utilization of patients with chronic conditions; 5 assessed mental health service utilization; 3 assessed resource utilization by a general population; and 1 assessed utilization in older populations. The most frequently measured resources included visits to general practitioners and inpatient stays; nonmedical resources were least frequently measured. Self-reported questionnaires on resource utilization had good agreement with administrative data, although, visits to general practitioners, outpatient days, and nurse visits had poorer agreement. Self-reported questionnaires are a valid method of collecting data on healthcare resource utilization. PMID:26962773

  5. Utility straight sections

    SciTech Connect

    Leemann, B.; Peggs, S.; Peterson, J.

    1985-10-01

    Utility straight sections are insertions in the SSC lattice to provide relatively free space to facilitate various beam manipulations. These uses include beam-abort, injection (and conceivably ejection), space for the rf system, and collimation. A typical utility straight section is 1500 meters in overall length (ranging from 500 to 1200 meters). It has zero dispersion and high values of the beta functions. The betatron phase shift across the insertion is about 90{degrees} in each plane.

  6. What do you do with the antiplatelet agents in patients with drug eluting stents who then receive a mechanical valve?

    PubMed Central

    Rossi, Michele; Serraino, Giuseppe Filiberto; Spadafora, Andrea; Renzulli, Attilio

    2012-01-01

    Dual antiplatelet therapy (DAT) with aspirin and clopidogrel is a cornerstone of treatment during and after percutaneous coronary interventions with drug-eluting stent (DES) implantation. Oral anticoagulation (OAC) is the recommended treatment for patients with mechanical heart valves. When patients with DES need a mechanical heart valve or vice versa, we face the difficult choice of their antithrombotic therapy. Different institutions empirically follow a combination of OAC and single or DAT, the so-called triple antithrombotic therapy (TT) aiming to find the best balance between the thrombotic and bleeding risk for this subset of patients. A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether there is an optimal antithrombotic management for patients with DES undergoing mechanical heart valve or vice versa. Altogether, more than 148 papers were found using the reported search, of which 16 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that DES implantation in patients who could potentially need valve surgery in the future should be discouraged and bare-metal stent or an aortic bioprosthesis preferred. However, in high-risk patients with DES, the recommendation is to postpone elective surgery for 1 year and, if surgery cannot be deferred, continue aspirin during the perioperative period. Moreover, when OAC is given in combination with clopidogrel and/or low-dose aspirin, the target INR should be 2.0–2.5 (Class IIb, level of evidence C). As per the long-term management, antithrombotic management with DAT alone in mechanical aortic valve replacement might be possible, but there is not enough evidence to support it. The available evidence suggests that triple anticoagulation (OAC + DAT) is associated with the best

  7. Long-term predictors of mortality after percutaneous coronary intervention in the era of drug-eluting stents.

    PubMed

    Wilson, William McLeish; Andrianopoulos, Nick; Clark, David; Duffy, Stephen James; Brennan, Angela; Harries, Iwan; New, Gishel; Sebastian, Martin; Loane, Philippa; Reid, Christopher; Ajani, Andrew Edward

    2011-10-01

    The aim was to examine timing, causes, and predictors of death during long-term follow-up after contemporary percutaneous coronary intervention (PCI) using a large multicenter Australian registry. The cohort consisted of 10,682 consecutive patients from the Melbourne Interventional Group registry undergoing PCI (February 2004 through November 2009). For the first time in Australia, long-term mortality rates of a PCI cohort were defined by linkage to the National Death Index database. The cohort (mean age 64 ± 12 years) comprised 75% men, 24% diabetics, 59% with multivessel disease, 4.4% with renal failure, 25% with ST-elevation myocardial infarction (STEMI), 2.5% with cardiogenic shock, and 5.1% with heart failure. Drug-eluting stents (DES) were used in 43% of cases. Mean follow-up was 3.2 ± 0.5 years. In-hospital, 30-day, 12-month, and long-term (3.2 ± 0.5 years) mortalities were 1.6% (80% cardiac), 2.1% (79%), 3.9% (61%), and 8.2% (50%), respectively. Independent predictors of long-term mortality included age (hazard ratio 1.05, 95% confidence interval 1.04 to 1.06), cardiogenic shock (4.58, 3.60 to 5.83), renal failure (3.14, 2.58 to 3.82), previous heart failure (1.97, 1.60 to 2.41), STEMI (1.79, 1.47 to 2.18), peripheral vascular disease (1.72, 1.4 to 2.11), non-STEMI (1.58, 1.32 to 1.90), multivessel disease (1.47, 1.24 to 1.74), current smoking (1.39, 1.12 to 1.71), diabetes (1.36, 1.16 to 1.59), and cerebrovascular disease (1.33, 1.06 to 1.60, p <0.01 for all comparisons). DES deployment appeared protective against late mortality (hazard ratio 0.85, 0.73 to 0.99, p = 0.04); however, after 30 days, there was no difference in mortality rates between those who received a bare metal stent and those who received a DES. In conclusion, different clinical variables such as renal and heart failure predicted long-term mortality after PCI, whereas DES use in this large registry was not associated with late mortality risk.

  8. The Impact of Renal Impairment on Long-Term Safety and Effectiveness of Drug-Eluting Stents

    PubMed Central

    Stefanini, Giulio G.; Taniwaki, Masanori; Kalesan, Bindu; Räber, Lorenz; Stortecky, Stefan; Pilgrim, Thomas; Onuma, Yoshinobu; Silber, Sigmund; Serruys, Patrick W.; Meier, Bernhard; Jüni, Peter; Windecker, Stephan

    2014-01-01

    Background Renal impairment (RI) is associated with impaired prognosis in patients with coronary artery disease. Clinical and angiographic outcomes of patients undergoing percutaneous coronary intervention (PCI) with the use of drug-eluting stents (DES) in this patient population are not well established. Methods We pooled individual data for 5,011 patients from 3 trials with the exclusive and unrestricted use of DES (SIRTAX - N = 1,012, LEADERS - N = 1,707, RESOLUTE AC - N = 2,292). Angiographic follow-up was available for 1,544 lesions. Outcomes through 2 years were stratified according to glomerular filtration rate (normal renal function: GFR≥90 ml/min; mild RI: 90

  9. Utility terrestrial biodiversity issues

    SciTech Connect

    Breece, G.A.; Ward, B.J.

    1996-11-01

    Results from a survey of power utility biologists indicate that terrestrial biodiversity is considered a major issued by only a few utilities; however, a majority believe it may be a future issue. Over half of the respondents indicated that their company is involved in some management for biodiversity, and nearly all feel that it should be a goal for resource management. Only a few utilities are funding biodiversity research, but a majority felt more research was needed. Generally, larger utilities with extensive land holdings had greater opportunities and resources for biodiversity management. Biodiversity will most likely be a concern with transmission rights-of-way construction and maintenance, endangered species issues and general land resource management, including mining reclamation and hydro relicensing commitments. Over half of the companies surveyed have established voluntary partnerships with management groups, and biodiversity is a goal in nearly all the joint projects. Endangered species management and protection, prevention of forest fragmentation, wetland protection, and habitat creation and protection are the most common partnerships involving utility companies. Common management practices and unique approaches are presented, along with details of the survey. 4 refs.

  10. Photovoltaics and electric utilities

    NASA Astrophysics Data System (ADS)

    Bright, R.; Leigh, R.; Sills, T.

    1981-12-01

    The long term value of grid connected, residential photovoltaic (PV) systems is determined. The value of the PV electricity is defined as the full avoided cost in accordance with the Public Utilities Regulatory Policies Act of 1978. The avoided cost is computed using a long range utility planning approach to measure revenue requirement changes in response to the time phased introduction of PV systems into the grid. A case study approach to three utility systems is used. The changing value of PV electricity over a twenty year period from 1985 is presented, and the fuel and capital savings due to FY are analyzed. These values are translated into measures of breakeven capital investment under several options of power interchange and pricing.

  11. Deregulation of electric utilities

    SciTech Connect

    Zaccour, G.

    1998-07-01

    This volume is a collection of fourteen, mainly applied, economic papers examining electric utility deregulation in many parts of the world. These papers were presented at the International Workshop on Deregulation of Electric Utilities held in Montreal, Canada in September 1997. As the title suggests, these papers cover a broad range of topics. Despite the book's scattershot approach, a small subset of contributors asks a fundamental question: Is the industry sufficiently deregulated? This book succeeds in providing some concrete and well-analyzed examples that examine this important question.

  12. Male Adolescent Contraceptive Utilization.

    ERIC Educational Resources Information Center

    Finkel, Madelon Lubin; Finkel, David J.

    1978-01-01

    The contraceptive utilization of a sample of sexually active, urban, high school males (Black, Hispanic, and White) was examined by anonymous questionnaire. Contraceptive use was haphazard, but White males tended to be more effective contraceptors than the other two groups. Reasons for nonuse were also studied. (Author/SJL)

  13. Module utilization committee

    NASA Technical Reports Server (NTRS)

    Volkmer, K.; Praver, G.

    1984-01-01

    Photovoltaic collector modules were declared surplus to the needs of the U.S. Dept. of Energy. The Module Utilization Committee was formed to make appropriate disposition of the surplus modules on a national basis and to act as a broker for requests for these modules originating outside of the National Photovoltaics Program.

  14. Administrative Utility Analysis: Appendices.

    ERIC Educational Resources Information Center

    Peat, Marwick, Mitchell and Co., San Juan, Puerto Rico.

    Appendixes to a study on administrative utility analysis and vocational education programs for the Area of Vocational and Technical Education (AVTE) in the Puerto Rico Department of Education contain the planning and budgeting system elements, position descriptions, and information on the growth of vocational education in Puerto Rico. The elements…

  15. Technology utilization program report

    NASA Technical Reports Server (NTRS)

    1974-01-01

    The application of aerospace technology to the solution of public health and industrial problems is reported. Data cover: (1) development of an externally rechargeable cardiac pacemaker, (2) utilization of ferrofluids-colloidal suspensions of ferrite particles - in the efficient separation of nonferrous metals as Ni, Zn, Cu, and Al from shredded automobile scrap, and (3) development of a breathing system for fire fighters.

  16. A Classroom Mathematics Utility.

    ERIC Educational Resources Information Center

    Williams, Michael

    1984-01-01

    Reviews CATUSPLOT, a mathematics utility aimed at high school algebra through college-level calculus. Basic program capabilities include plotting, tabulating, integrating, and locating of intersections of functions composed of combinations of polynomial, trigonometric, and exponential functions. Rated excellent on all areas examined…

  17. Utilities. [univac computer programs

    NASA Technical Reports Server (NTRS)

    Colquitt, W. N.

    1976-01-01

    Several sets of related Adage utility programs are described. A general description of the software group, instructions on how to use the programs, and a programmers description of the theory of operation are given along with a printed example of the program in use and a listing of the program.

  18. Employment Tax Credit Utilization.

    ERIC Educational Resources Information Center

    Parkinson, Jan

    Utilizing data collected through a national survey of employers, the impact of federal tax credit programs for employers of Work Incentive Program (WIN) participants and Aid to Families with Dependent Children (AFDC) recipients was assessed. Six major questions were addressed: (1) What differences there were in the use of the WIN and welfare tax…

  19. Classroom Use and Utilization.

    ERIC Educational Resources Information Center

    Fink, Ira

    2002-01-01

    Discusses how classrooms are distributed by size on a campus, how well they are used, and how their use changes with faculty and student needs and desires. Details how to analyze classroom space, use, and utilization, taking into account such factors as scheduling and classroom stations. (EV)

  20. NASA technology utilization house

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Following systems and features, which are predicted to save approximately $20,000 in utility costs over twenty year period, are incorporated into single-level, contemporarily designed, energy efficient residential structure: solar heating and cooling; energy efficient appliances; water recycling; security, smoke, and tornado detectors; and flat conductor electrical wiring.

  1. Readability: Computer Utilization.

    ERIC Educational Resources Information Center

    Felsenthal, Helen

    Textual Analysis of Language Samples (TEXAN) is a computer program which can count a number of variables needed for use in readability formulas. Three studies which utilize TEXAN are reported in this paper: (1) In 1972, Norman and Helen Felsenthal randomly selected 20 books from the 1306 in Eakin's "Good Books for Children" and calculated their…

  2. Inhibition of plaque neovascularization and intimal hyperplasia by specific targeting vascular endothelial growth factor with bevacizumab-eluting stent: an experimental study.

    PubMed

    Stefanadis, Christodoulos; Toutouzas, Konstantinos; Stefanadi, Elli; Lazaris, Andreas; Patsouris, Efstratios; Kipshidze, Nicholas

    2007-12-01

    Neovascularization is associated with destabilization of atheromatic plaques. Increased expression of vascular endothelial growth factor (VEGF) is important in the process of neovascularization. We assessed the effect of bevacizumab, a monoclonal antibody specific for VEGF, on neovascularization. We used 12 New Zealand rabbits under atherogenic diet for 3 weeks. We immersed a phosphorycholine coated stent into a solution of 4 ml bevacizumab according to previous studies. Twelve eluting stents and 12 non-eluting stents were implanted in the middle segment of the rabbit's iliac arteries. Follow-up angiography was performed at 4 weeks and tissues were obtained for histological analysis. The procedure of stent loading with bevacizumab and stent implantation was successful. There was no difference in angiographic measurements before, after implantation and at follow-up between the two groups. mean neointimal thickness (0.09+/-0.02 versus 0.12+/-0.02 mm, p<0.01), and mean neointimal area (1.08+/-0.09 versus 1.20+/-0.12 mm(2), p<0.01) were less in the bevacizumab treated segments. bevacizumab-treated arterial segments demonstrated significantly decreased microvessel density compared with the control group (1.69+/-0.06 CI: 1.65-1.73 versus 15.68+/-0.56 CI: 15.32-16.04 vessels per mm(2), p<0.001) and vegf expression was decreased in the media and adventitia of bevacizumab group. Endothelialization, inflammation and injury scores were similar between the two groups. These results suggest that bevacizumab-eluting stent implantation in rabbit iliac arteries is safe, and inhibits neovascularization without affecting the endothelialization.

  3. Nonvascular drug-eluting stent coated with sodium caprate-incorporated polyurethane for the efficient penetration of paclitaxel into tumor tissue.

    PubMed

    Jeong, Dooyong; Lee, Don Haeng; Lee, Dong Ki; Na, Kun

    2015-03-01

    To increase the therapeutic potency of nonvascular drug-eluting stents, sodium caprate was employed as a drug-penetration enhancer. A polytetrafluoroethylene-covered drug-eluting stent was coated with a mixture containing sodium caprate, paclitaxel, and polyurethane via the rolling coating technique. The coated stent has a smooth membrane surface with a 40-µm membrane thickness. Paclitaxel was released from the coated stent for two months. In the multilayered cell sheet model, sodium caprate in the polyurethane membrane (PUSC10) showed the possibility of enhancing the paclitaxel tissue penetration. The amount of penetrated paclitaxel for the sodium caprate-containing polyurethane membrane (PUSC10) was two times higher than that of sodium caprate-free polyurethane membrane. Additionally, the potential of sodium caprate was confirmed by a tumor-bearing small animal model. PUSC10 incorporated with Nile red (as a model fluorescence dye for visualization of drug penetration; PUSC10-Nile red) or PUSC10 incorporated with paclitaxel (PUSC10-paclitaxel) membrane was implanted at tumor sites in Balb/c mice. In the case of PUSC10-Nile red, the tissue penetration depth of Nile red was significantly increased from 30 µm (without sodium caprate) to 1060 µm (with sodium caprate). After seven days, an almost four times higher therapeutic area of PUSC10-paclitaxel was observed compared to that of polyurethane-paclitaxel (without sodium caprate) by a terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The results indicate that sodium caprate improves the penetration and therapeutic efficiencies of drugs in drug-eluting stents, and thus, it has potential for local stent therapy.

  4. Simultaneous Measurements of Eight Oxyanions Using High-Capacity Diffusive Gradients in Thin Films (Zr-Oxide DGT) with a High-Efficiency Elution Procedure.

    PubMed

    Ding, Shiming; Xu, Di; Wang, Yanping; Wang, Yan; Li, Yangyang; Gong, Mengdan; Zhang, Chaosheng

    2016-07-19

    A zirconium oxide binding gel-based diffusive gradients in thin films (Zr-oxide DGT) was developed for simultaneous measurements of P(V), As(V), Cr(VI), Mo(VI), Sb(V), Se(VI), V(V), and W(VI). All of the oxyanions were rapidly bound to Zr-oxide gel with differences in binding affinity. The eight bound oxyanions were successfully recovered by one-step elution using a mild reagent of 0.2 M NaOH-0.5 M H2O2 by overcoming the problems in analyses of the oxyanions. The optimized elution time was reduced to 3-5 h from 24-48 h required by other DGTs. DGT uptakes of all the oxyanions were independent of pH (4.42-8.45) and ionic strength (0.1-500 mM). The DGT capacities for six oxyanions detected in multioxyanion solution were only 0.19 to 0.35 times of those detected in single-oxyanion solution, reflecting a strong competition among the oxyanions during DGT uptake. Except for Se(VI) in seawater, Zr-oxide DGT accurately measured all of the oxyanions in synthetic freshwater and seawater, with the capacities ∼29 to >2397 times and ∼7.5 to 232 times those of two commonly used DGTs (Metsorb and precipitated ferrihydrite (PF) DGTs) in freshwater and seawater, respectively. Measurements by Zr-oxide DGT in contaminated sediments were in agreement with only two oxyanions with the two commonly used DGTs; the two DGTs accumulated less or no mass of other oxyanions. This study demonstrates significant advantage of Zr-oxide DGT over the other DGTs in simultaneous measurements of the eight oxyanions due to the former's high capacity and a wide tolerance to environmental interferences, together with a high efficiency in elution. PMID:27303914

  5. Coupling frontal elution paper chromatography with desorption corona beam ionization mass spectrometry for rapid analysis of chlorphenamine in herbal medicines and dietary supplements.

    PubMed

    Huang, Yun-Qing; You, Jing-Qing; Zhang, Junsheng; Sun, Wenjian; Ding, Li; Feng, Yu-Qi

    2011-10-14

    We developed a convenient method by coupling frontal elution paper chromatography with desorption corona beam ionization mass spectrometry (DCBI-MS) for rapid determination of chlorphenamine added in herbal medicines or dietary supplements. In this method, the ethanol extract of the herbal products was spotted directly onto an isosceles triangular filter paper sheet, and then the paper sheet was developed under strong elution condition with the sample zone migrating at the solvent front. The analyte was finally condensed at the V-shaped tip which could then be placed under the visible plasma beam of DCBI for ionization. The overall procedure took less than 5 min. The frontal elution paper chromatography on a triangular plate used in this work improved the signal intensity of chlorphenamine by 30-fold due to the analyte condensing at the tip and the reduction of the background suppression. Furthermore, the paper sheet also functioned as a filter in the analysis of solid or powder samples, which can increase the analytical throughput by omitting the step of centrifugation. The proposed method in current study was successfully applied in the determination of chlorphenamine in herbal medicines. Chlorphenamine was detected in four of the twelve types of herbal medicines examined in this study. The limit of detection was 200 ng/mL (2.0 ng absolute) in full-scan positive-ion mode and the linear range was from 5.0 μg/mL to 50 μg/mL with satisfactory linear coefficient (R(2) (the square of the correlation coefficient)=0.895). Good reproducibility was achieved with relative standard deviations (RSDs) less than 15.0% and the recoveries of chlorphenamine ranged from 84.3 to 90.6%.

  6. Drug loading and elution from a phosphorylcholine polymer-coated coronary stent does not affect long-term stability of the coating in vivo.

    PubMed

    Lewis, Andrew L; Willis, Sean L; Small, Sharon A; Hunt, Stuart R; O'byrne, Vincent; Stratford, Peter W

    2004-01-01

    A drug eluting coronary stent was developed for use in preclinical and clinical trial evaluation. The stent was coated with a phosphorylcholine (PC)-based polymer coating containing the cell migration inhibitor batimastat. A pharmacokinetic study was conducted in a rabbit iliac model using (14)C-radiolabeled version of the drug; this showed the drug release to be first order with 94% of it being released within 28 days. Unloaded and drug-loaded stents were implanted in a porcine coronary artery model; a number were explanted at 5 days and scanning electron microscopy was used to show that the presence of the drug did not affect the rate of stent endothelialization. The remainder of the stents were removed after 6 months and the stents carefully removed from the arterial tissue. Fourier-transform infrared (FT-IR) spectroscopy (both attenuated total reflectance and microscopic imaging) was used to show the presence of the PC coating on control unloaded, drug-loaded and explanted stents, providing evidence that the coating was still present. This was further confirmed by use of atomic force microscopy (AFM) amplitude-phase, distance (a-p,d) curves which generated the characteristic traces of the PC coating. Further AFM depth-profiling techniques found that the thicknesses of the PC coatings on an control unloaded stent was 252+/-19 nm, on an control batimastat-loaded stent 906+/-224 nm and on an explanted stent 405+/-224 nm. The increase in thickness after the drug-loading process was a consequence of drug incorporation in the film, and the return to the unloaded dimensions for the explanted sample indicative of elution of the drug from the coating. The drug delivery PC coating was therefore found to be stable following elution of the drug and after 6 months implantation in vivo. PMID:15472385

  7. A bio-artificial poly([d,l]-lactide-co-glycolide) drug-eluting nanofibrous periosteum for segmental long bone open fractures with significant periosteal stripping injuries

    PubMed Central

    Chou, Ying-Chao; Cheng, Yi-Shiun; Hsu, Yung-Heng; Yu, Yi-Hsun; Liu, Shih-Jung

    2016-01-01

    Biodegradable poly([d,l]-lactide-co-glycolide) (PLGA) nanofibrous membrane embedded with two drug-to-polymer weight ratios, namely 1:3 and 1:6, which comprised PLGA 180 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg, and PLGA 360 mg, lidocaine 20 mg, vancomycin 20 mg, and ceftazidime 20 mg, respectively, was produced as an artificial periosteum in the treatment of segmental femoral fractures. The nanofibrous membrane’s drug release behavior was assessed in vitro using high-performance liquid chromatography and the disk-diffusion method. A femoral segmental fracture model with intramedullary Kirschner-wire fixation was established for the in vivo rabbit activity study. Twenty-four rabbits were divided into two groups. Twelve rabbits in group A underwent femoral fracture fixation only, and 12 rabbits in group B underwent femoral fracture fixation and were administered the drug-loaded nanofibers. Radiographs obtained at 2, 6, and 12 weeks postoperatively were used to assess the bone unions. The total activity counts in animal behavior cages were also examined to evaluate the clinical performance of the rabbits. After the animals were euthanized, both femoral shafts were harvested and assessed for their torque strengths and toughness. The daily in vitro release curve for lidocaine showed that the nanofibers eluted effective levels of lidocaine for longer than 3 weeks. The bioactivity studies of vancomycin and ceftazidime showed that both antibiotics had effective and sustained bactericidal capacities for over 30 days. The findings from the in vivo animal activity study suggested that the rabbits with the artificial drug-eluting periosteum exhibited statistically increased levels of activity and better clinical performance outcomes compared with the rabbits without the artificial periosteum. In conclusion, this artificial drug-eluting periosteum may eventually be used for the treatment of open fractures. PMID:27022261

  8. Detachable strong cation exchange monolith, integrated with capillary zone electrophoresis and coupled with pH gradient elution, produces improved sensitivity and numbers of peptide identifications during bottom-up analysis of complex proteomes.

    PubMed

    Zhang, Zhenbin; Yan, Xiaojing; Sun, Liangliang; Zhu, Guijie; Dovichi, Norman J

    2015-04-21

    A detachable sulfonate-silica hybrid strong cation-exchange monolith was synthesized in a fused silica capillary, and used for solid phase extraction with online pH gradient elution during capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) proteomic analysis. Tryptic digests were prepared in 50 mM formic acid and loaded onto the strong cation-exchange monolith. Fractions were eluted using a series of buffers with lower concentration but higher pH values than the 50 mM formic acid background electrolyte. This combination of elution and background electrolytes results in both sample stacking and formation of a dynamic pH junction and allows use of relatively large elution buffer volumes while maintaining reasonable peak efficiency and resolution. A series of five pH bumps were applied to elute E. coli tryptic peptides from the monolith, followed by analysis using CZE coupled to an LTQ-Orbitrap Velos mass spectrometer; 799 protein groups and 3381 peptides were identified from 50 ng of the digest in a 2.5 h analysis, which approaches the identification rate for this organism that was obtained with an Orbitrap Fusion. We attribute the improved numbers of peptide and protein identifications to the efficient fractionation by the online pH gradient elution, which decreased the complexity of the sample in each elution step and improved the signal intensity of low abundance peptides. We also performed a comparative analysis using a nanoACQUITY UltraPerformance LCH system. Similar numbers of protein and peptide identifications were produced by the two methods. Protein identifications showed significant overlap between the two methods, whereas peptide identifications were complementary.

  9. A detachable strong cation exchange monolith, integrated with capillary zone electrophoresis and coupled with pH gradient elution, produces improved sensitivity and numbers of peptide identifications during bottom-up analysis of complex proteomes

    PubMed Central

    Zhang, Zhenbin; Yan, Xiaojing; Sun, Liangliang; Zhu, Guijie; Dovichi, Norman J.

    2015-01-01

    A detachable sulfonate-silica hybrid strong cation-exchange monolith was synthesized in a fused silica capillary, and used for solid phase extraction with on-line pH gradient elution during capillary zone electrophoresis-tandem mass spectrometry (CZE-MS/MS) proteomic analysis. Tryptic digests were prepared in 50 mM formic acid and loaded onto the strong cation-exchange monolith. Fractions were eluted using a series of buffers with lower concentration but higher pH values than the 50 mM formic acid background electrolyte. This combination of elution and background electrolytes results in both sample stacking and formation of a dynamic pH junction, and allows use of relatively large elution buffer volumes while maintaining reasonable peak efficiency and resolution. A series of five pH bumps were applied to elute E. coli tryptic peptides from the monolith, followed by analysis using CZE coupled to an LTQ-Orbitrap Velos mass spectrometer; 799 protein groups and 3,381 peptides were identified from 50 ng of the digest in a 2.5 hour analysis, which approaches the identification rate for this organism that was obtained with an Orbitrap Fusion. We attribute the improved numbers of peptide and protein identifications to the efficient fractionation by the on-line pH gradient elution, which decreased the complexity of the sample in each elution step and improved the signal intensity of low abundance peptides. We also performed a comparative analysis using a nanoACQUITY UltraPerformance LCH system. Similar numbers of protein and peptide identifications were produced by the two methods. Protein identifications showed significant overlap between the two methods, whereas peptide identifications were complementary. PMID:25822566

  10. MTV Utility Library

    2008-02-29

    The MSV Java Utility Library contains software developed over many years for many sponsors. (This work is not a derivative of CB-EMIS), but rather support to the CB-EMIS software). Projects that have used and contributed to code in this library: CB-EMIS (PROTECT), BWIC, Fort Future, Teva, Integrated Oceans, ENKIMDU, RCW, JEMS, JWACS, EPA watershed, and many others. This library will continue to be used in other non-CB-EMIS related projects. The components include: Spatial components: Multi-coordinatemore » system spatial objects. 2D spatial indexing system, and polygon griding system. Data translation: Allows import and export of file based data to and from object oriented systems. Multi-platform data streams: Allows platform specific data streams to operate on any support platform. Other items include printing, custom GUI components, support for NIMA Raster Product Format, program logging utilities and others.« less

  11. MTV Utility Library

    SciTech Connect

    Lurie, Gordon; Taxon, Thomas; Kehrer, Michelle; Simunich, Kathy Lee

    2008-02-29

    The MSV Java Utility Library contains software developed over many years for many sponsors. (This work is not a derivative of CB-EMIS), but rather support to the CB-EMIS software). Projects that have used and contributed to code in this library: CB-EMIS (PROTECT), BWIC, Fort Future, Teva, Integrated Oceans, ENKIMDU, RCW, JEMS, JWACS, EPA watershed, and many others. This library will continue to be used in other non-CB-EMIS related projects. The components include: Spatial components: Multi-coordinate system spatial objects. 2D spatial indexing system, and polygon griding system. Data translation: Allows import and export of file based data to and from object oriented systems. Multi-platform data streams: Allows platform specific data streams to operate on any support platform. Other items include printing, custom GUI components, support for NIMA Raster Product Format, program logging utilities and others.

  12. MVUSRS utility reference manual

    SciTech Connect

    Brengle, T.A.

    1985-11-01

    The MVUSRS utility assists in the moving of TOPS-10/20 user accounts to VMS systems. MVUSRS runs on the source TOPS-10/20 system and combines user account information from the TOPS system (from REACT on TOPS-10 or from DLUSER on TOPS-20) with input from the operator of the utility to generate a VMS DCL COM file. This COM file can then be shipped to the target VMS system and executed. MVUSRS is known to work with TOPS-10 Version 4.01, TOPS-20 Version 5.1, and VMS Version 4.1. Other versions may work, but have not been tested. In particular, it is unlikely that MVUSRS will work with versions of VMS prior to 4.0 since much has been made of the enhanced user account information available in Version 4.0. The MVUSRS source listing is provided. (DWL)

  13. NASA's Technology Utilization Program.

    NASA Technical Reports Server (NTRS)

    Farley, C. F.

    1972-01-01

    NASA's Technology Utilization Program is described, illustrating how it can be useful in achieving improved productivity, providing more jobs, solving public sector challenges, and strengthening the international competitive situation. Underlying the program is the fact that research and development conducted in NASA's aeronautics and space programs have generated much technical information concerning processes, products, or techniques which may be useful to engineers, doctors, or to others. The program is based on acquisition and publication, working with the user, and applications engineering.

  14. Utility avoids cooling tower

    SciTech Connect

    1994-08-01

    After more than four years of often rancorous debate, New Jersey late last month approved a plan that permits the state`s largest utility to reclaim and restore Delaware Bay marshland instead of constructing a costly cooling tower for two nuclear power units. Environmental interests say they`ll appeal the wetlands proposal, calling it an {open_quotes}unproven experiment{close_quotes} that violates Clean Water Act provisions.

  15. Seasat data utilization project

    NASA Technical Reports Server (NTRS)

    Born, G. H.; Held, D. N.; Lame, D. B.; Lipes, R. G.; Montgomery, D. R.; Rygh, P. J.; Scott, J. F.

    1981-01-01

    During the three months of orbital operations, the satellite returned data from the world's oceans. Dozens of tropical storms, hurricanes and typhoons were observed, and two planned major intensive surface truth experiments were conducted. The utility of the Seasat-A microwave sensors as oceanographic tools was determined. Sensor and geophysical evaluations are discussed, including surface observations, and evaluation summaries of an altimeter, a scatterometer, a scanning multichannel microwave radiometer, a synthetic aperture radar, and a visible and infrared radiometer.

  16. Energy utilization in phonation

    NASA Astrophysics Data System (ADS)

    Krane, Michael

    2015-11-01

    A control volume analysis of energy utilization in phonation is presented. Conversion of subglottal airstream potential energy into work done vibrating the vocal folds, air flowing through the glottis, and radiating sound are described. An approximate numerical model is used to compute the contributions of each of these mechanisms, as a function of subglottal pressure, for normal phonation. An efficiency measure for each energy conversion mechanism is proposed. Acknowledge NIH grant 2R01 2R01DC005642.

  17. Ethics for electic utilities

    SciTech Connect

    Powers, C.W.; Toffler, B.L. )

    1991-05-15

    This article examines the ethical challenges of remaining honest and fair when the playing field of competition does not appear to be level. Topics discussed include measuring performance, monitoring use of services, public opinion of utility integrity and commitment to service, making ethical concerns and language a part of the management decision process, and communication of moral issues to a place where resolution can occur.

  18. Separation of polyphenols from leaves of Malus hupehensis (Pamp.) Rehder by off-line two-dimensional High Speed Counter-Current Chromatography combined with recycling elution mode.

    PubMed

    Liu, Qi; Zeng, Hualiang; Jiang, Shujing; Zhang, Li; Yang, Fuzhu; Chen, Xiaoqing; Yang, Hua

    2015-11-01

    In this study, off-line two-dimensional High Speed Counter-Current Chromatography (2D HSCCC) strategy combined with recycling elution mode was developed to isolate compounds from the ethyl acetate extract of a common green tea--leaves of Malus hupehensis (Pamp.) Rehder. In the orthogonal separation system, a conventional HSCCC was employed for the first dimension and two recycling HSCCCs were used for the second in parallel. Using a solvent system consisting of n-hexane-ethyl acetate-methanol-water (1:4:0.6:4.4, v/v) in the first and second dimension, four compounds including 3-hydroxy-phlorizin (1), phloretin (2), avicularin (3) and kaempferol 3-O-β-D-glucoside (4) were obtained. The purities of these four compounds were all over 95.0% as determined by HPLC. And their structures were all identified through UV, MS and (1)H NMR. It has been demonstrated that the combination of off-line 2D HSCCC with recycling elution mode is an efficient technique to isolate compounds with similar polarities in natural products.

  19. Efficacy of Drug-Eluting Balloons for Patients With In-Stent Restenosis: A Meta-Analysis of 8 Randomized Controlled Trials.

    PubMed

    Gao, Shen; Shen, Jing; Mukku, Venkata Kishore; Wang, Mei Jia; Akhtar, Muzina; Liu, Wei

    2016-08-01

    The optimal treatment for in-stent restenosis (ISR) of both bare-metal stent (BMS) and drug-eluting stent (DES) is currently unclear. The aim of this meta-analysis was to assess the role of drug-eluting balloon (DEB) as an optional treatment for ISR. We searched PubMed, MEDLINE, EMBASE, BIOS, and Web of Science from 2005 to July 2014. Eight studies, enrolling 1413 patients were included. Main end points were late lumen loss (LLL), binary in-segment restenosis (BR), major adverse cardiac events (MACEs), target lesion revascularization (TLR), death, myocardial infarction (MI), and stent thrombosis (ST). When compared to plain old balloon angioplasty (POBA), DEB treatment significantly reduced the risk of MACE (risk rato [RR] 0.37, P < .01), death (RR 0.44, P = .04), TLR (RR 0.27, P < .01), BR (RR [95% CI]: 0.23[0.12 to 0.43], P < .01) and associated with better outcomes of LLL ( 0.50 [ 0.65 to 0.35] mm, P < .01). However, the differences were not significant between DEB treatment and DES treatment in all primary and secondary end points. The DEB was a better option to treat ISR when compared to POBA. However, it had similar effects as DES.

  20. Risk Factors for Coronary Drug-Eluting Stent Thrombosis: Influence of Procedural, Patient, Lesion, and Stent Related Factors and Dual Antiplatelet Therapy

    PubMed Central

    Hermiller, James B.; Ferguson, Joanne M.; Simonton, Charles A.

    2013-01-01

    The complication of stent thrombosis (ST) emerged at a rate of 0.5% annually for first-generation drug-eluting stents (DES), often presenting as death or myocardial infarction. Procedural factors such as stent underexpansion and malapposition are risk factors for ST in patients. The type of lesion being treated and lesion morphology also influence healing after treatment with DES and can contribute to ST. Second-generation DES such as the XIENCE V everolimus-eluting stent differ from the first-generation stents with respect to antiproliferative agents, coating technologies, and stent frame. Improvements in stent structure have resulted in a more complete endothelialization, thereby decreasing the incidence of ST. Bioresorbable scaffolds show promise for restoring vasomotor function and minimizing rates of very late ST. Post-PCI treatment with aspirin and clopidogrel for a year is currently the standard of care for DES, but high-risk patients may benefit from more potent antiplatelet agents. The optimal duration of DAPT for DES is currently unclear and will be addressed in large-scale randomized clinical trials. PMID:23862074

  1. Clinical Outcomes from Unselected "Real-World" Patients with Long Coronary Lesion Receiving 40 mm Biodegradable Polymer Coated Sirolimus-Eluting Stent.

    PubMed

    Polavarapu, Anurag; Polavarapu, Raghava Sarma; Prajapati, Jayesh; Thakkar, Kamlesh; Raheem, Asif; Mayall, Tamanpreet; Thakkar, Ashok

    2015-01-01

    Background. Long lesions being implanted with drug-eluting stents (DES) are associated with relatively high restenosis rates and higher incidences of adverse events. Objectives. We aimed to examine the safety and efficacy of the long (40 mm) biodegradable polymer coated Indolimus sirolimus-eluting stent (SES) in real-world patients with long coronary lesions. Methods. This study was observational, nonrandomized, retrospective, and carried out in real-world patients. A total of 258 patients were enrolled for the treatment of long coronary lesions, with 40 mm Indolimus. The primary endpoints in the study were incidence of major adverse cardiac events (MACE), a miscellany of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) or target vessel revascularization (TVR), and stent thrombosis (ST) up to 6-month follow-up. Results. The study population included higher proportion of males (74.4%) and average age was 53.2 ± 11.0 years. A total of 278 lesions were intervened successfully with 280 stents. The observed MACE at 6-month follow-up was 2.0%, which included 0.8% cardiac death and 1.2% MI. There were no TLR or TVR and ST observed during 6-month follow-up. Conclusions. The long (40 mm) Indolimus stent demonstrated low MACE rate and was proven to be safe and effective treatment for long lesions in "real-world" patients.

  2. Clinical Outcomes from Unselected “Real-World” Patients with Long Coronary Lesion Receiving 40 mm Biodegradable Polymer Coated Sirolimus-Eluting Stent

    PubMed Central

    Polavarapu, Anurag; Polavarapu, Raghava Sarma; Prajapati, Jayesh; Thakkar, Kamlesh; Raheem, Asif; Mayall, Tamanpreet; Thakkar, Ashok

    2015-01-01

    Background. Long lesions being implanted with drug-eluting stents (DES) are associated with relatively high restenosis rates and higher incidences of adverse events. Objectives. We aimed to examine the safety and efficacy of the long (40 mm) biodegradable polymer coated Indolimus sirolimus-eluting stent (SES) in real-world patients with long coronary lesions. Methods. This study was observational, nonrandomized, retrospective, and carried out in real-world patients. A total of 258 patients were enrolled for the treatment of long coronary lesions, with 40 mm Indolimus. The primary endpoints in the study were incidence of major adverse cardiac events (MACE), a miscellany of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) or target vessel revascularization (TVR), and stent thrombosis (ST) up to 6-month follow-up. Results. The study population included higher proportion of males (74.4%) and average age was 53.2 ± 11.0 years. A total of 278 lesions were intervened successfully with 280 stents. The observed MACE at 6-month follow-up was 2.0%, which included 0.8% cardiac death and 1.2% MI. There were no TLR or TVR and ST observed during 6-month follow-up. Conclusions. The long (40 mm) Indolimus stent demonstrated low MACE rate and was proven to be safe and effective treatment for long lesions in “real-world” patients. PMID:26579328

  3. Study of bond Elut® Plexa™ PCX cation exchange resin in flow injection column preconcentration system for metal determination by flame atomic absorption spectrometry.

    PubMed

    Anthemidis, Aristidis N; Xidia, Sofia; Giakisikli, Georgia

    2012-08-15

    A simple and sensitive on-line solid-phase extraction methodology for preconcentration and determination of trace amounts of Cd(II), Pd(II) and Cu(II) in natural water samples has been developed using the strong cation exchange capability of Bond Elut(®) Plexa™ PCX polymer resin. Plexa PCX is a mixed-mode sorbent, commercially available in a cartridge format and as far as we know, there is no application into the field of metal determination. The analytes were retained on the resin, eluted with 1 mol L(-1) hydrochloric acid and subsequently directed to FAAS for quantification. The influence of chemical and flow variables which affect the performance of the system have been studied, providing the appropriate conditions for the analysis of real samples. For preconcentration time of 90 s, an enrichment factor of 90, 95 and 95 and a detection limit (3 s) of 0.1, 1.8 and 0.5 μg L(-1) for Cd(II), Pb(II) and Cu(II), respectively were obtained along with a sampling frequency of 30 h(-1). The accuracy of the proposed method was evaluated by analyzing certified reference materials. This procedure was successfully applied for metal determination in environmental and biological samples. PMID:22841064

  4. Immune complex glomerulonephritis in experimental kala-azar. II: Detection and characterization of parasite antigens and antibodies eluted from kidneys of Leishmania donovani-infected hamsters.

    PubMed Central

    Sartori, A; Roque-Barreira, M C; Coe, J; Campos-Neto, A

    1992-01-01

    In a previous report analysing kidney sections by immunofluorescence we showed that hamsters infected with L. donovani develop a glomerulonephritis (GN) associated with deposition of hamster immunoglobulins and parasite antigens in the glomeruli. In this study we characterize these immune components eluted from the kidneys. The eluted immunoglobulins showed specificity for L. donovani antigens and hamster immunoglobulins (rheumatoid factor-like activity). The four isotypes IgG1, IgG2, IgA and IgM were detected. Several L. donovani antigens were detected in the renal eluates by Western blot and immunoprecipitation using 125I-labelled eluates. Proteins with mol. wt of 134, 82, 52, 31, and 26 kD were detected by Western blot and proteins with 134, 110, 93, 89 and 48 kD were detected by immunoprecipitation. With the exception of the 134 kD protein which was recognized by both rabbit anti-promastigote and rabbit anti-amastigote sera all the others were recognized only by the anti-amastigote serum. The 134 kD protein was the only one isolated from the kidneys of infected hamster immunocomplexed with IgG and was the only one detected in a promastigote lysate using IgG from L. donovani-infected hamsters. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:1544224

  5. Novel Approaches to the Management of Advanced Peripheral Artery Disease: Perspectives on Drug-Coated Balloons, Drug-Eluting Stents, and Bioresorbable Scaffolds.

    PubMed

    Zeller, Thomas; Rastan, Aljoscha; Macharzina, Roland; Beschorner, Ulrich; Noory, Elias

    2015-09-01

    Introducing anti-restenotic drug-based treatment modalities in femoropopliteal interventions is the potential revolutionizing reperfusion treatment of peripheral artery disease. Durability of recanalization procedures using drug-coated balloons (DCB) and drug-eluting stents (DES) yields in excellent mid-term and long-term technical and clinical outcomes and may be cost saving on the long term as compared to traditional treatment modalities such as plain old balloon angioplasty (POBA) and bare metal nitinol stent implantation. Drug-eluting bioresorbable scaffolds are another drug-based promising treatment option but are still investigational. In particular, DCB provide a novel method to locally deliver paclitaxel into the arterial wall without the need of a chronically implanted delivery system or even if those devices will be indicated, they can be delivered focally. Following the first positive pilot studies, two large pivotal trials have confirmed superiority of DCB over plain old balloon angioplasty (POBA) in the treatment of TASC II A and B femoropopliteal lesions. Even for more complex femoropopliteal lesions such as long lesions and instent restenosis, single center studies and small randomized studies have shown promising mid-term technical and clinical results. For DES, follow-up data for the only commercially available device are now presented up to 5 years with excellent clinical outcome regarding freedom from target lesion revascularization and improvement of walking capacity. This review article summarizes the current knowledge and perspectives of drug-based endovascular treatment modalities in femoropopliteal interventions and discusses still unresolved needs.

  6. Preliminary Evaluation of Clinical and Angiographic Outcomes with Biodegradable Polymer Coated Sirolimus-Eluting Stent in De Novo Coronary Artery Disease: Results of the MANIPAL-FLEX Study

    PubMed Central

    Prajapati, Jayesh; Pai, Umesh; Shetty, Kiran

    2016-01-01

    Objective. The objective of the MANIPAL-FLEX study was to evaluate the feasibility, preliminary safety, and efficacy of the Supraflex sirolimus-eluting stent (SES) implantation, in de novo coronary artery disease, using clinical and quantitative coronary angiography (QCA) follow-ups. Methods. This was a prospective, nonrandomized, multicenter, single-arm study that enrolled 189 patients with de novo coronary artery disease who were treated with the Supraflex SES. Of 189 patients enrolled, the first 61 consecutive patients who consented to a 9-month follow-up evaluation by QCA, irrespective of presence of symptoms, were to be followed up with angiography at 9 months. The primary endpoint of the study was target lesion failure (TLF), including cardiac death, myocardial infarction, and target lesion revascularization during 12-month follow-up after the index procedure. Results. The mean age of the study population was 58 ± 11 years, with 51.3% (97/189) of hypertensive patients. Total of 66 lesions, analyzed by offline QCA, showed good scaffolding of the target vessel with in-stent late lumen loss at 9 months of 0.18 ± 0.23 mm. The observed TLF at 30-day, 6-month, and 12-month follow-up were 2 (1.1%), 6 (3.2%), and 10 (5.3%), respectively. Conclusion. This study provides preliminary evidence for the feasibility, safety, and efficacy of the Supraflex sirolimus-eluting stent.

  7. Elution of antibiotics from poly(methyl methacrylate) bone cement after extended implantation does not necessarily clear the infection despite susceptibility of the clinical isolates.

    PubMed

    Swearingen, Matthew C; Granger, Jeffrey F; Sullivan, Anne; Stoodley, Paul

    2016-02-01

    Chronic orthopedic infections are commonly caused by bacterial biofilms, which are recalcitrant to antibiotic treatment. In many cases, the revision procedure for periprosthetic joint infection or trauma cases includes the implantation of antibiotic-loaded bone cement to kill infecting bacteria via the elution of a strong local dose of antibiotic(s) at the site. While many studies have addressed the elution kinetics of both non-absorbable and absorbable bone cements both in vitro and in vivo, the potency of ALBC against pathogenic bacteria after extended implantation time is not clear. In this communication, we use two case studies, a Viridans streptococci infected total knee arthroplasty (TKA) and a MRSA-polymicrobial osteomyelitis of a distal tibial traumatic amputation (TA) to demonstrate that an antibiotic-loaded poly(methyl methacrylate) (ALPMMA) coated intermedullary rod implanted for 117 days (TKA) and three ALPMMA suture-strung beads implanted for 210 days (TA) retained killing ability against Pseudomonas aeruginosa and Staphylococcus aureus in vitro, despite different clinical efficacies. The TKA infection resolved and the patient progressed to an uneventful second stage. However, the TA infection only resolved after multiple rounds of debridement, IV vancomycin and removal of the PMMA beads and placement of vancomycin and tobramycin loaded calcium sulfate beads.

  8. Electropolymerized tricopolymer based on N-pyrrole derivatives as a primer coating for improving the performance of a drug-eluting stent.

    PubMed

    Okner, Regina; Shaulov, Yulia; Tal, Noam; Favaro, Gregory; Domb, Abraham J; Mandler, Daniel

    2009-04-01

    The coating of medical implants by polymeric films aims at increasing their biocompatibility as well as providing a durable matrix for the controlled release of a drug. In many cases, the coating is divided into a primer layer, which bridges between the medical implant and the drug-eluting matrix. The primer coating must be very carefully designed in order to provide optimal interactions with the surface of the medical implant and the outer layer. Here we present a simple and versatile approach for designing the primer layer based on electropolymerization of a carefully chosen blend of three different pyrrole derivatives: N-methylpyrrole (N-me), N-(2-carboxyethyl)pyrrole (PPA), and the butyl ester of N-(2-carboxyethyl)pyrrole (BuOPy). The composition and physical properties of the primer layer were studied in detail by atomic force microscopy (AFM) and a nano scratch tester. The latter provides the in-depth analysis of the adhesion and viscoelasticity of the coating. AFM phase imaging reveals a uniform distribution of the three monomers forming rough morphology. This primer layer significantly improved the morphology, stability, and paclitaxel release profile of a paclitaxel-eluting matrix based on methyl and lauryl methacrylates.

  9. Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma.

    PubMed

    Park, Wooram; Chen, Jeane; Cho, Soojeong; Park, Sin-Jung; Larson, Andrew C; Na, Kun; Kim, Dong-Hyun

    2016-05-25

    Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug-eluting beads (DEB) were developed for transcatheter IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. It can be difficult to control drug loading/release from DEB and to monitor selective delivery to the targeted tumors. Embolized DEBs in hepatic arteries frequently induce hypoxic and low pH conditions, promoting cancer cell growth. In this study, an acidic pH-triggered drug-eluting nanocomposite (pH-DEN) including superparamagnetic iron oxide nanocubes and pH-responsive synthetic peptides with lipid tails [octadecylamine-p(API-l-Asp)10] was developed for magnetic resonance imaging (MRI)-monitored transcatheter delivery of sorafenib (the only FDA-approved systemic therapy for liver cancer) to HCC. The synthesized sorafenib-loaded pH-DENs exhibited distinct pH-triggered drug release behavior at acidic pH levels and highly sensitive MR contrast effects. In an orthotopic HCC rat model, successful hepatic IA delivery and distribution of sorafenib-loaded pH-DEN was confirmed with MRI. IA-delivered sorafenib-loaded pH-DENs elicited significant tumor growth inhibition in a rodent HCC model. These results indicate that the sorafenib-pH-DENs platform has the potential to be used as an advanced tool for liver-directed IA treatment of unresectable HCC.

  10. Preliminary Evaluation of Clinical and Angiographic Outcomes with Biodegradable Polymer Coated Sirolimus-Eluting Stent in De Novo Coronary Artery Disease: Results of the MANIPAL-FLEX Study.

    PubMed

    Shetty, Ranjan; Prajapati, Jayesh; Pai, Umesh; Shetty, Kiran

    2016-01-01

    Objective. The objective of the MANIPAL-FLEX study was to evaluate the feasibility, preliminary safety, and efficacy of the Supraflex sirolimus-eluting stent (SES) implantation, in de novo coronary artery disease, using clinical and quantitative coronary angiography (QCA) follow-ups. Methods. This was a prospective, nonrandomized, multicenter, single-arm study that enrolled 189 patients with de novo coronary artery disease who were treated with the Supraflex SES. Of 189 patients enrolled, the first 61 consecutive patients who consented to a 9-month follow-up evaluation by QCA, irrespective of presence of symptoms, were to be followed up with angiography at 9 months. The primary endpoint of the study was target lesion failure (TLF), including cardiac death, myocardial infarction, and target lesion revascularization during 12-month follow-up after the index procedure. Results. The mean age of the study population was 58 ± 11 years, with 51.3% (97/189) of hypertensive patients. Total of 66 lesions, analyzed by offline QCA, showed good scaffolding of the target vessel with in-stent late lumen loss at 9 months of 0.18 ± 0.23 mm. The observed TLF at 30-day, 6-month, and 12-month follow-up were 2 (1.1%), 6 (3.2%), and 10 (5.3%), respectively. Conclusion. This study provides preliminary evidence for the feasibility, safety, and efficacy of the Supraflex sirolimus-eluting stent. PMID:27597929

  11. Clinical Outcomes from Unselected "Real-World" Patients with Long Coronary Lesion Receiving 40 mm Biodegradable Polymer Coated Sirolimus-Eluting Stent.

    PubMed

    Polavarapu, Anurag; Polavarapu, Raghava Sarma; Prajapati, Jayesh; Thakkar, Kamlesh; Raheem, Asif; Mayall, Tamanpreet; Thakkar, Ashok

    2015-01-01

    Background. Long lesions being implanted with drug-eluting stents (DES) are associated with relatively high restenosis rates and higher incidences of adverse events. Objectives. We aimed to examine the safety and efficacy of the long (40 mm) biodegradable polymer coated Indolimus sirolimus-eluting stent (SES) in real-world patients with long coronary lesions. Methods. This study was observational, nonrandomized, retrospective, and carried out in real-world patients. A total of 258 patients were enrolled for the treatment of long coronary lesions, with 40 mm Indolimus. The primary endpoints in the study were incidence of major adverse cardiac events (MACE), a miscellany of cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) or target vessel revascularization (TVR), and stent thrombosis (ST) up to 6-month follow-up. Results. The study population included higher proportion of males (74.4%) and average age was 53.2 ± 11.0 years. A total of 278 lesions were intervened successfully with 280 stents. The observed MACE at 6-month follow-up was 2.0%, which included 0.8% cardiac death and 1.2% MI. There were no TLR or TVR and ST observed during 6-month follow-up. Conclusions. The long (40 mm) Indolimus stent demonstrated low MACE rate and was proven to be safe and effective treatment for long lesions in "real-world" patients. PMID:26579328

  12. Poly-(L-lactic acid) and citric acid-crosslinked gelatin composite matrices as a drug-eluting stent coating material with endothelialization, antithrombogenic, and drug release properties.

    PubMed

    Inoue, Motoki; Sasaki, Makoto; Katada, Yasuyuki; Fujiu, Katsuhito; Manabe, Ichiro; Nagai, Ryozo; Taguchi, Tetsushi

    2013-07-01

    Biodegradable composite matrices comprising poly-(L-lactic acid) (PLLA) and citric acid-crosslinked alkali-treated gelatin (AlGelatin) with endothelialization, antithrombogenic, and drug release properties were prepared. The characterization of composite matrices with various mixing ratios was performed by evaluating their swelling ratio, endothelial cell culture, antithrombogenic tests, and drug release behavior. Tamibarotene (Am80), which specifically inhibits smooth muscle cell proliferation, was employed as the drug. The swelling ratio of composite matrices decreased as the PLLA content decreased. The number of endothelial cells cultured on the surfaces of composite matrices was maximal at the PLLA/AlGelatin-TSC ratio of 80/20. Antithrombogenic tests revealed that the levels of platelets and fibrin network formation decreased as the AlGelatin-TSC content increased. The Am80 release test indicated that the release rate decreased as PLLA content increased. Using the resulting composite matrix, Am80-eluting stents possessing a smooth surface and a coating thickness of ∼15 μm were successfully obtained. Am80 was continuously released from the resulting stent at ∼40%, up to 28 days without burst release. Therefore, Am80-eluting stent with its antithrombogenic and endothelialization properties has great potential for clinical use.

  13. Prediction of the retention of s-triazines in reversed-phase high-performance liquid chromatography under linear gradient-elution conditions.

    PubMed

    D'Archivio, Angelo Antonio; Maggi, Maria Anna; Ruggieri, Fabrizio

    2014-08-01

    In this paper, a multilayer artificial neural network is used to model simultaneously the effect of solute structure and eluent concentration profile on the retention of s-triazines in reversed-phase high-performance liquid chromatography under linear gradient elution. The retention data of 24 triazines, including common herbicides and their metabolites, are collected under 13 different elution modes, covering the following experimental domain: starting acetonitrile volume fraction ranging between 40 and 60% and gradient slope ranging between 0 and 1% acetonitrile/min. The gradient parameters together with five selected molecular descriptors, identified by quantitative structure-retention relationship modelling applied to individual separation conditions, are the network inputs. Predictive performance of this model is evaluated on six external triazines and four unseen separation conditions. For comparison, retention of triazines is modelled by both quantitative structure-retention relationships and response surface methodology, which describe separately the effect of molecular structure and gradient parameters on the retention. Although applied to a wider variable domain, the network provides a performance comparable to that of the above "local" models and retention times of triazines are modelled with accuracy generally better than 7%.

  14. Safety and efficacy of a novel iopromide-based paclitaxel-eluting balloon following bare metal stent implantation in rabbit aorta abdominalis

    PubMed Central

    Zhu, Zhengbin; Han, Hui; Zhu, Jinzhou; Zhang, Jing; Du, Run; Ni, Jingwei; Ying, Chen; An, Xuanqi; Zhang, Ruiyan

    2015-01-01

    BACKGROUND: Drug-eluting balloons (DEB) may be promising technology for treating atherosclerotic arterial disease. In fact, several DEBs have been clinically available for the treatment of coronary in-stent restenosis (ISR), de novo coronary lesions, and peripheral artery disease. OBJECTIVE: We sought to elucidate the mechanism of action and in vivo safety and efficacy of a novel iopromide-based paclitaxel-eluting balloon. METHODS: In vitro cytotoxicity of a novel DEB on human umbilical vein endothelial cells (HUVECs) and in vivo pharmacokinetics of DEB in a rabbit aorta abdominalis were assessed. Then, bare metal stents (BMS) were implanted at both the proximal and distal sites of the rabbit aorta abdominalis. Stented vascular segments were immediately dilated with a bare balloon (control group) or the DEB (DEB group) randomly. Histological evaluation was performed in all treated segments at 28 days. Because paclitaxel is a tubulin-disrupting agent that binds preferentially to β-tubulin, we measured β-tubulin expression in aortal stent specimens via immunohistochemistry. RESULTS: We observed that DEB was compatible and could reduce neointimal hyperplasia compared with the bare balloon. Meanwhile, immunohistochemistry revealed that β-tubulin expression in the DEB group increased compared with the control group, indirectly suggesting successful uptake of paclitaxel by vessel walls after DEB dilation. CONCLUSIONS: The novel DEB is safe and has a favorable vascular healing response on neointimal hyperplasia. PMID:26484558

  15. Preliminary Evaluation of Clinical and Angiographic Outcomes with Biodegradable Polymer Coated Sirolimus-Eluting Stent in De Novo Coronary Artery Disease: Results of the MANIPAL-FLEX Study

    PubMed Central

    Prajapati, Jayesh; Pai, Umesh; Shetty, Kiran

    2016-01-01

    Objective. The objective of the MANIPAL-FLEX study was to evaluate the feasibility, preliminary safety, and efficacy of the Supraflex sirolimus-eluting stent (SES) implantation, in de novo coronary artery disease, using clinical and quantitative coronary angiography (QCA) follow-ups. Methods. This was a prospective, nonrandomized, multicenter, single-arm study that enrolled 189 patients with de novo coronary artery disease who were treated with the Supraflex SES. Of 189 patients enrolled, the first 61 consecutive patients who consented to a 9-month follow-up evaluation by QCA, irrespective of presence of symptoms, were to be followed up with angiography at 9 months. The primary endpoint of the study was target lesion failure (TLF), including cardiac death, myocardial infarction, and target lesion revascularization during 12-month follow-up after the index procedure. Results. The mean age of the study population was 58 ± 11 years, with 51.3% (97/189) of hypertensive patients. Total of 66 lesions, analyzed by offline QCA, showed good scaffolding of the target vessel with in-stent late lumen loss at 9 months of 0.18 ± 0.23 mm. The observed TLF at 30-day, 6-month, and 12-month follow-up were 2 (1.1%), 6 (3.2%), and 10 (5.3%), respectively. Conclusion. This study provides preliminary evidence for the feasibility, safety, and efficacy of the Supraflex sirolimus-eluting stent. PMID:27597929

  16. Time Functions as Utilities

    NASA Astrophysics Data System (ADS)

    Minguzzi, E.

    2010-09-01

    Every time function on spacetime gives a (continuous) total preordering of the spacetime events which respects the notion of causal precedence. The problem of the existence of a (semi-)time function on spacetime and the problem of recovering the causal structure starting from the set of time functions are studied. It is pointed out that these problems have an analog in the field of microeconomics known as utility theory. In a chronological spacetime the semi-time functions correspond to the utilities for the chronological relation, while in a K-causal (stably causal) spacetime the time functions correspond to the utilities for the K + relation (Seifert’s relation). By exploiting this analogy, we are able to import some mathematical results, most notably Peleg’s and Levin’s theorems, to the spacetime framework. As a consequence, we prove that a K-causal (i.e. stably causal) spacetime admits a time function and that the time or temporal functions can be used to recover the K + (or Seifert) relation which indeed turns out to be the intersection of the time or temporal orderings. This result tells us in which circumstances it is possible to recover the chronological or causal relation starting from the set of time or temporal functions allowed by the spacetime. Moreover, it is proved that a chronological spacetime in which the closure of the causal relation is transitive (for instance a reflective spacetime) admits a semi-time function. Along the way a new proof avoiding smoothing techniques is given that the existence of a time function implies stable causality, and a new short proof of the equivalence between K-causality and stable causality is given which takes advantage of Levin’s theorem and smoothing techniques.

  17. Coming utility squeeze play

    SciTech Connect

    Stoiaken, L.N.

    1988-02-01

    Like a sleeping giant, utilities are waking up and preparing to participate in the increasingly competitive power production industry. Some are establishing subsidiaries to participate in join venture deals with independents. Others are competing by offering lucrative discount or deferral rates to important industrial and commercial customers considering cogeneration. And now, a third approach is beginning to shape up- the disaggregation of generation assets into a separate generation company, or genco. This article briefly discusses these three and also devotes brief sections to functional segmentation and The regulatory arena.

  18. Tribal Utility Feasibility Study

    SciTech Connect

    Engel, R. A.; Zoellick, J. J.

    2007-06-30

    The Schatz Energy Research Center (SERC) assisted the Yurok Tribe in investigating the feasibility of creating a permanent energy services program for the Tribe. The original purpose of the DOE grant that funded this project was to determine the feasibility of creating a full-blown Yurok Tribal electric utility to buy and sell electric power and own and maintain all electric power infrastructure on the Reservation. The original project consultant found this opportunity to be infeasible for the Tribe. When SERC took over as project consultant, we took a different approach. We explored opportunities for the Tribe to develop its own renewable energy resources for use on the Reservation and/or off-Reservation sales as a means of generating revenue for the Tribe. We also looked at ways the Tribe can provide energy services to its members and how to fund such efforts. We identified opportunities for the development of renewable energy resources and energy services on the Yurok Reservation that fall into five basic categories: • Demand-side management – This refers to efforts to reduce energy use through energy efficiency and conservation measures. • Off-grid, facility and household scale renewable energy systems – These systems can provide electricity to individual homes and Tribal facilities in areas of the Reservation that do not currently have access to the electric utility grid. • Village scale, micro-grid renewable energy systems - These are larger scale systems that can provide electricity to interconnected groups of homes and Tribal facilities in areas of the Reservation that do not have access to the conventional electric grid. This will require the development of miniature electric grids to serve these interconnected facilities. • Medium to large scale renewable energy development for sale to the grid – In areas where viable renewable energy resources exist and there is access to the conventional electric utility grid, these resources can be

  19. Classical subjective expected utility.

    PubMed

    Cerreia-Vioglio, Simone; Maccheroni, Fabio; Marinacci, Massimo; Montrucchio, Luigi

    2013-04-23

    We consider decision makers who know that payoff-relevant observations are generated by a process that belongs to a given class M, as postulated in Wald [Wald A (1950) Statistical Decision Functions (Wiley, New York)]. We incorporate this Waldean piece of objective information within an otherwise subjective setting à la Savage [Savage LJ (1954) The Foundations of Statistics (Wiley, New York)] and show that this leads to a two-stage subjective expected utility model that accounts for both state and model uncertainty. PMID:23559375

  20. TRW utility demonstration unit

    SciTech Connect

    Not Available

    1990-01-01

    The TRW Advanced Entrained Coal Combustor Demonstration Project consists of retrofitting Orange and Rockland (O R) Utility Corporation's Lovett Plant Unit No. 3 with four (4) slagging combustors which will allow the gas/oil unit to fire 2.5% sulfur coal. The slagging combustor process will provide NO{sub x} and SO{sub x} emissions that meet NSPS and New York State Environmental Standards. During this report period, activity continued to address the total program funding shortfall. Ideas and responsibilities for further evaluation have been put forward to reduce the shortfall. In addition, an effort aimed at gaining additional program sponsorships, was initiated.

  1. Space Resources Utilization Roundtable

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This volume contains abstracts that have been accepted for presentation at the Space Resources Utilization Roundtable, October 27-29, 1999, in Golden, Colorado. The program committee consisted of M. B. Duke (Lunar and Planetary Institute), G. Baughman (Colorado School of Mines), D. Criswell (University of Houston), C. Graham (Canadian Mining Industry Research Organization), H. H. Schmitt (Apollo Astronaut), W. Sharp (Colorado School of Mines), L. Taylor (University of Tennessee), and a space manufacturing representative. Administration and publications support for this meeting were provided by the staff of the Publications and Program Services Department at the Lunar and Planetary Institute.

  2. Biogas: Production and utilization

    NASA Astrophysics Data System (ADS)

    Price, E. C.; Cheremisinoff, P. N.

    Among the aspects of biogas production and utilization covered are: (1) the microbiology and biochemistry of the acid and methane production stages in the anaerobic process; (2) factors affecting the process, such as temperature, acidity and alkalinity, nutrients, and cations; (3) denitrification processes and systems; and (4) the process kinetics of suspended growth systems, packed columns, and fluidized beds. Also considered are such issues in the application of this technology as the digestion of municipal treatment plant sludges, animal wastes, food processing wastes and energy crops. Attention is in addition given to anaerobic digester design, offgas measurement of anaerobic digesters, and sludge treatment through soil conditioning and composting.

  3. Resource recovery utility

    SciTech Connect

    Jones, R.L.

    1987-02-17

    This patent describes a resource recovery utility comprising: (i) a landfill; (ii) a continuous wall surrounding the perimeter of the landfill; (iii) a containment structure extending completely over the landfill and affixed to the continuous wall; (iv) means for introducing refuse into the landfill; (v) means for compacting the refuse; (vi) means for removing and recovering methane generated by anaerobic bacterial digestion of organic materials contained in the refuse; and (vii) means for removing at least a portion of the compacted refuse from the landfill.

  4. Utility Static Generation Reliability

    1993-03-05

    PICES (Probabilistic Investigation of Capacity and Energy Shortages) was developed for estimating an electric utility''s expected frequency and duration of capacity deficiencies on a daily on and off-peak basis. In addition to the system loss-of-load probability (LOLP) and loss-of-load expectation (LOLE) indices, PICES calculates the expected frequency and duration of system capacity deficiencies and the probability, expectation, and expected frequency and duration of a range of system reserve margin states. Results are aggregated and printedmore » on a weekly, monthly, or annual basis. The program employs hourly load data and either the two-state (on/off) or a more sophisticated three-state (on/partially on/fully off) generating unit representation. Unit maintenance schedules are determined on a weekly, levelized reserve margin basis. In addition to the 8760-hour annual load record, the user provides the following information for each unit: plant capacity, annual maintenance requirement, two or three-state unit failure and repair rates, and for three-state models, the partial state capacity deficiency. PICES can also supply default failure and repair rate values, based on the Edison Electric Institute''s 1979 Report on Equipment Availability for the Ten-Year Period 1968 Through 1977, for many common plant types. Multi-year analysis can be performed by specifying as input data the annual peak load growth rates and plant addition and retirement schedules for each year in the study.« less

  5. Lunar construction utility vehicle

    NASA Technical Reports Server (NTRS)

    1989-01-01

    The lunar construction utility vehicle (LCUV) is an all-purpose construction vehicle which will aid in the robotic assembly of a lunar outpost. The LCUV will have the following capabilities: (1) must be self supporting including repairs; (2) must offload itself from a lunar lander; (3) must be telerobotic and semi-autonomous; (4) must be able to transport one space station common module; (5) must allow for man-rated operation; and (6) must be able to move lunar regolith for site preparation. This study recommends the use of an elastic tracked vehicle. Detailed material analyses of most of the LCUV components were accomplished. The body frame, made of pinned truss elements, was stress analyzed using NASTRAN. A track connection system was developed; however, kinematic and stress analyses are still required. This design recommends the use of hydrogen-oxygen fuel cells for power. Thermal control has proven to be a problem which may be the most challenging technically. A tentative solution has been proposed which utilizes an onboard and towable radiator. Detailed study of the heat dissipation requirements is needed to finalize radiator sizing. Preliminary work on a man-rated cabin has begun; however, this is not required during the first mission phase of the LCUV. Finally, still in the conceptual phases, are the communication, navigation and mechanical arm systems.

  6. Overloaded elution band profiles of ionizable compounds in reversed-phase liquid chromatography: Influence of the competition between the neutral and the ionic species

    SciTech Connect

    Gritti, Fabrice; Guiochon, Georges A

    2008-01-01

    The parameters that affect the shape of the band profiles of acido-basic compounds under moderately overloaded conditions (sample size less than 500 nmol for a conventional column) in RPLC are discussed. Only analytes that have a single pK{sub a} are considered. In the buffer mobile phase used for their elution, their dissociation may, under certain conditions, cause a significant pH perturbation during the passage of the band. Two consecutive injections (3.3 and 10 {micro}L) of each one of three sample solutions (0.5, 5, and 50 mM) of ten compounds were injected on five C{sub 18}-bonded packing materials, including the 5 {micro}m Xterra-C{sub 18} (121 {angstrom}), 5 {micro}m Gemini-C{sub 18} (110 {angstrom}), 5 {micro}m Luna-C{sub 18}(2) (93 {angstrom}), 3.5 {micro}m Extend-C{sub 18} (80 {angstrom}), and 2.7 {micro}m Halo-C{sub 18} (90 {angstrom}). The mobile phase was an aqueous solution of methanol buffered at a constant {sub W}{sup W}pH of 6, with a phosphate buffer. The total concentration of the phosphate groups was constant at 50 mM. The methanol concentration was adjusted to keep all the retention factors between 1 and 10. The compounds injected were phenol, caffeine, 3-phenyl 1-propanol, 2-phenyl butyric acid, amphetamine, aniline, benzylamine, p-toluidine, procainamidium chloride, and propranololium chloride. Depending on the relative values of the analyte pK{sub a} and the buffer solution pH, these analytes elute as the neutral, the cationic, or the anionic species. The influence of structural parameters such as the charge, the size, and the hydrophobicity of the analytes on the shape of its overloaded band profile is discussed. Simple but general rules predict these shapes. An original adsorption model is proposed that accounts for the unusual peak shapes observed when the analyte is partially dissociated in the buffer solution during its elution.

  7. Does endovascular treatment of infra-inguinal arterial disease with drug-eluting stents offer better results than angioplasty with or without bare metal stents?

    PubMed

    Antoniou, George A; Georgakarakos, Efstratios I; Antoniou, Stavros A; Georgiadis, George S

    2014-08-01

    A best evidence topic in vascular and endovascular surgery was developed according to a structured protocol. The question addressed was whether treatment of infra-inguinal arterial occlusive disease with drug-eluting stents (DESs) provides improved outcomes compared with bare metal stents (BMSs) or percutaneous balloon angioplasty (PTA) alone. Altogether, 136 papers were found using the reported searches, of which 5 provided the best evidence to answer the question. All papers represent either level 1 or 2 evidence. The authors, journal, date, country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Main outcome measures varied among the studies, and included patency, in-stent restenosis, target lesion revascularization, major adverse events, clinical improvement and limb salvage. Evidence on the comparative efficacy of DESs in femoro-popliteal arterial disease is mainly based on two randomized, controlled trials. Paclitaxel-eluting stents were evaluated in the Zilver PTX trial and demonstrated superior 2-year results to either BMSs or PTA, as indicated/shown by patency (DES vs PTA, 74.8 vs 26.5%, P < 0.01), clinical benefit (DES vs PTA, P < 0.01) and event-free survival (DES vs PTA, 86.6 vs 77.9%, P = 0.02). However, the SIROCCO trial found that the sirolimus-eluting stent did not exhibit statistically significant differences in 2-year in-stent restenosis (22.9 vs 21.1%) and target lesion revascularization (6 vs 13%) compared with the BMS. Treatment of infra-politeal arterial disease with DESs was related with superior outcomes to those of BMSs, as indicated/shown by patency, freedom from target lesion revascularization and freedom from major adverse events. Furthermore, the ACHILLES trial, the only published trial comparing the infra-popliteal DES with PTA, revealed lower angiographic restenosis (22.4 vs 41.9%, P = 0.019) and greater vessel patency (75 vs 57.1%, P = 0.025) in the DES group at 1 year

  8. Can Platforms Affect the Safety and Efficacy of Drug-Eluting Stents in the Era of Biodegradable Polymers?: A Meta-Analysis of 34,850 Randomized Individuals

    PubMed Central

    Zhang, Ming-Duo; Li, Xin-He; Nie, Mao-Xiao; Feng, Ting-Ting; Zhao, Xin; Wang, Lu-Ya; Zhao, Quan-Ming

    2016-01-01

    Objective In the era of bare metal stents (BMSs), alloys have been considered to be better materials for stent design than stainless steel. In the era of biodegradable polymer drug-eluting stents (BP-DESs), the safety and efficacy of BP-DESs with different metal platforms (stainless steel or alloys) have not yet been reported, although their polymers are eventually absorbed, and only the metal platforms remain in the body. This study sought to determine the clinical safety and efficacy of BP-DESs with different platforms compared with other stents (other DESs and BMSs). Methods PubMed, Embase and Clinical Trials.gov were searched for randomized controlled trials (RCTs) that compared BP-DESs with other stents. After performing pooled analysis of BP-DESs and other stents, we performed a subgroup analysis using two classification methods: stent platform and follow-up time. The study characteristics, patient characteristics and clinical outcomes were abstracted. Results Forty RCTs (49 studies) comprising 34,850 patients were included. Biodegradable polymer stainless drug-eluting stents (BP-stainless DESs) were superior to the other stents [mainly stainless drug-eluting stents (DESs)] in terms of pooled definite/probable stent thrombosis (ST) (OR [95% CI] = 0.76[0.61–0.95], p = 0.02), long-term definite/probable ST (OR [95% CI] = 0.73[0.57–0.94], p = 0.01), very late definite/probable ST (OR [95% CI] = 0.56[0.33–0.93], p = 0.03) and long-term definite ST. BP-stainless DESs had lower rates of pooled, mid-term and long-term target vessel revascularization (TVR) and target lesion revascularization (TLR) than the other stainless DESs and BMSs. Furthermore, BP-stainless DESs were associated with lower rates of long-term death than other stainless DESs and lower rates of mid-term myocardial infarction than BMSs. However, only the mid-term and long-term TVR rates were superior in BP-alloy DESs compared with the other stents. Conclusion Our results indirectly suggest that

  9. Sex differences in long-term outcomes of coronary patients treated with drug-eluting stents at a tertiary medical center

    PubMed Central

    Shammas, Nicolas W; Shammas, Gail A; Jerin, Michael; Sharis, Peter

    2014-01-01

    Background Limited data exist on contemporary sex-related differences in long-term outcomes of coronary patients receiving drug-eluting stents. In this study we evaluate differences for males (M) and females (F) in 2-year target lesion failure (TLF) in an unselected consecutive series of patients treated with everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES) at a tertiary medical center. Methods Data on 348 consecutive patients (M 221, F 127) stented with EES and PES were retrospectively analyzed. The primary end point of the study was to compare sex-related outcomes in TLF, defined as the combined end point of cardiac death, nonfatal myocardial infarction, and target lesion revascularization (TLR). Secondary end points included TLR, target vessel failure, target vessel revascularization, acute stent thrombosis as defined by the Academic Research Consortium, and cardiac death. The cineangiograms of the first consecutive 162 patients (M 105, F 57) were independently reviewed by a cardiologist blinded to clinical outcome, and SYNTAX scoring was performed. Follow-up was achieved using medical records and/or phone calls and was censored at 2 years. Descriptive analysis was performed on all variables. Univariate analysis compared the M and F cohorts. Multivariate analysis using Cox regression was performed to determine independent predictors of TLF with time, including sex as an independent variable in the model. Results M had more prior percutaneous coronary interventions and restenotic lesions and a higher prevalence of smoking. They also had longer length of disease and received more stents than F. F were older and had a higher prevalence of prior stroke. Angiographic complexity was not statistically different between the two groups, as judged by SYNTAX scoring (M 20.8±13.8, F 19.7±13.9, P=0.650). At 2-year follow-up, TLF was 27.4% and 24.8% (P=0.614) with no statistical difference between TLR (23.3% versus [vs] 21.6%), cardiac death (2.8% vs 3

  10. Optimal Electric Utility Expansion

    1989-10-10

    SAGE-WASP is designed to find the optimal generation expansion policy for an electrical utility system. New units can be automatically selected from a user-supplied list of expansion candidates which can include hydroelectric and pumped storage projects. The existing system is modeled. The calculational procedure takes into account user restrictions to limit generation configurations to an area of economic interest. The optimization program reports whether the restrictions acted as a constraint on the solution. All expansionmore » configurations considered are required to pass a user supplied reliability criterion. The discount rate and escalation rate are treated separately for each expansion candidate and for each fuel type. All expenditures are separated into local and foreign accounts, and a weighting factor can be applied to foreign expenditures.« less

  11. Asteroid exploration and utilization

    NASA Technical Reports Server (NTRS)

    Radovich, Brian M.; Carlson, Alan E.; Date, Medha D.; Duarte, Manny G.; Erian, Neil F.; Gafka, George K.; Kappler, Peter H.; Patano, Scott J.; Perez, Martin; Ponce, Edgar

    1992-01-01

    The Earth is nearing depletion of its natural resources at a time when human beings are rapidly expanding the frontiers of space. The resources possessed by asteroids have enormous potential for aiding and enhancing human space exploration as well as life on Earth. Project STONER (Systematic Transfer of Near Earth Resources) is based on mining an asteroid and transporting raw materials back to Earth. The asteroid explorer/sample return mission is designed in the context of both scenarios and is the first phase of a long range plan for humans to utilize asteroid resources. Project STONER is divided into two parts: asteroid selection and explorer spacecraft design. The spacecraft design team is responsible for the selection and integration of the subsystems: GNC, communications, automation, propulsion, power, structures, thermal systems, scientific instruments, and mechanisms used on the surface to retrieve and store asteroid regolith. The sample return mission scenario consists of eight primary phases that are critical to the mission.

  12. Proteomics: capacity versus utility.

    PubMed

    Harry, J L; Wilkins, M R; Herbert, B R; Packer, N H; Gooley, A A; Williams, K L

    2000-04-01

    Until recently scientists studied genes or proteins one at a time. With improvements in technology, new tools have become available to study the complex interactions that occur in biological systems. Global studies are required to do this, and these will involve genomic and proteomic approaches. High-throughput methods are necessary in each case because the number of genes and proteins in even the simplest of organisms are immense. In the developmental phase of genomics, the emphasis was on the generation and assembly of large amounts of nucleic acid sequence data. Proteomics is currently in a phase of technological development and establishment, and demonstrating the capacity for high throughput is a major challenge. However, funding bodies (both in the public and private sector) are increasingly focused on the usefulness of this capacity. Here we review the current state of proteome research in terms of capacity and utility.

  13. Acetonitrile shortage: use of isopropanol as an alternative elution system for ultra/high performance liquid chromatography†

    PubMed Central

    Desai, Ankur M.; Andreae, Mark; Mullen, Douglas G.; Holl, Mark M. Banaszak; Baker, James R.

    2010-01-01

    Acetonitrile is a choice of solvent for almost all chromatographic separations. In recent years, researchers around the globe have faced an acetonitrile shortage that affected routine analytical operations. Researchers have tried to counter this shortage by applying many innovative solutions, including using ultra performance liquid chromatography (UPLC) columns that are shorter and smaller in diameter than traditional high performance liquid chromatography (HPLC) columns, thus significantly decreasing the volume of eluent required. Although utilizing UPLC in place of HPLC can alleviate the solvent demand to some extent, acetonitrile is generally thought of as the solvent of choice due to its versatility. In the following communication, we describe an alternative eluent system that uses isopropanol in place of acetonitrile as an organic modifier for routine chromatographic separations. We report here the development of an isopropanol based UPLC protocol for G5 PAMAM dendrimer based conjugates that was transferred to semi-preparative applications. PMID:21572563

  14. Preparative isolation and purification of macrolactin antibiotics from marine bacterium Bacillus amyloliquefaciens using high-speed counter-current chromatography in stepwise elution mode.

    PubMed

    He, Shan; Wang, Hongqiang; Yan, Xiaojun; Zhu, Peng; Chen, Juanjuan; Yang, Rui

    2013-01-11

    Preparative high-speed counter-current chromatography (HSCCC) was successfully applied to the isolation and purification of two macrolactin antibiotics from marine bacterium Bacillus amyloliquefaciens for the first time using stepwise elution with a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water at (1:4:1:4, v/v) and (3:4:3:4, v/v). The preparative HSCCC separation was performed on 300 mg of crude sample yielding macrolactin B (22.7 mg) and macrolactin A (40.4 mg) in a one-step separation, with purities over 95% as determined by HPLC. The structures of these compounds were identified by MS, (1)H NMR and (13)C NMR. Our results demonstrated that HSCCC was an efficient technique to separate marine antibiotics, which provide an approach to solve the problem of their sample availability for drug development.

  15. Intractable intraoperative bleeding requiring platelet transfusion during emergent cholecystectomy in a patient with dual antiplatelet therapy after drug-eluting coronary stent implantation (with video)

    PubMed Central

    Fujikawa, Takahisa; Noda, Tomohiro; Tada, Seiichiro; Tanaka, Akira

    2013-01-01

    We report a case of a 76-year-old man, receiving dual antiplatelet therapy (DAPT) with aspirin and ticlopidine for the past 6 years after implantation of drug-eluting coronary stent, developed a severe hypochondriac pain. After diagnosing severe acute cholecystitis by an enhanced CT, emergent laparotomy under continuation of DAPT was attempted. During the operation, intractable bleeding from the adhesiolysed liver surface was encountered, which required platelet transfusion. Subtotal cholecystectomy with abdominal drainage was performed, and the patient recovered without any postoperative bleeding or thromboembolic complications. Like the present case, the final decision should be made to perform platelet transfusion when life-threatening DAPT-induced intraoperative bleeding occurs during an emergent surgery, despite the elevated risk of stent thrombosis. PMID:23536626

  16. Successful treatment of bleeding large duodenal gastrointestinal stromal tumour in a patient under dual antiplatelet therapy after recent drug-eluting coronary stent implantation

    PubMed Central

    Fukuyama, Keita; Fujikawa, Takahisa; Kuramitsu, Shoichi; Tanaka, Akira

    2014-01-01

    We report a case of a 69-year-old man who started dual antiplatelet therapy (APT) with aspirin and clopidogrel after recent implantation of drug-eluting coronary stent and developed massive bleeding due to large duodenal gastrointestinal stromal tumour (GIST). Following endoscopic haemostasis and discontinuation of dual APT, neoadjuvant chemotherapy with imatinib was started under continuation of ‘single’ APT with aspirin. A good chemotherapeutic response was achieved without recurrence of bleeding, and subsequent less invasive surgical resection of the tumour was performed, while preoperative single APT was continued for prevention of stent thrombosis. The patient recovered well without any thromboembolic or bleeding events. Neoadjuvant imatinib therapy and subsequent less invasive surgery under continuation of APT is one of the preferred approaches for patients with duodenal GIST with severe thromboembolic comorbidities, as in the current case. PMID:24777088

  17. Evaluation of Elution and Mechanical Properties of High-Dose Antibiotic-Loaded Bone Cement: Comparative "In Vitro" Study of the Influence of Vancomycin and Cefazolin.

    PubMed

    Paz, Eva; Sanz-Ruiz, Pablo; Abenojar, Juana; Vaquero-Martín, Javier; Forriol, Francisco; Del Real, Juan Carlos

    2015-08-01

    Use of antibiotic-loaded bone cements is one of the most effective methods for the prevention and treatment of prosthetic joint infection. However, there is still controversy about the optimal combination and doses of antibiotics that provide the maximum antimicrobial effect without compromising cement properties. In this study, vancomycin and cefazolin were added to a bone cement (Palacos R+G). Antibiotic release, fluid absorption, and mechanical properties were evaluated under physiological conditions. The results show that the type of antibiotic selected has an important impact on cement properties. In this study, groups with cefazolin showed much higher elution than those containing the same concentration of vancomycin. In contrast, groups with cefazolin showed a lower strength than vancomycin groups.

  18. Novel balloon catheter device with pacing, ablating, electroporation, and drug-eluting capabilities for atrial fibrillation treatment--preliminary efficacy and safety studies in a canine model.

    PubMed

    DeSimone, Christopher V; Ebrille, Elisa; Syed, Faisal F; Mikell, Susan B; Suddendorf, Scott H; Wahnschaffe, Douglas; Ladewig, Dorothy J; Gilles, Emily J; Danielsen, Andrew J; Holmes, David R; Asirvatham, Samuel J

    2014-12-01

    Pulmonary vein isolation is an established therapeutic procedure for symptomatic atrial fibrillation (AF). This approach involves ablation of atrial tissue just outside the pulmonary veins. However, patient outcomes are limited because of a high rate of arrhythmia recurrence. Ablation of electrically active tissue inside the pulmonary vein may improve procedural success, but is currently avoided because of the complication of postablation stenosis. An innovative device that can ablate inside pulmonary veins and prevent stenosis is a viable strategy to increase long-term efficacy. We have developed a prototypical balloon catheter device capable of nonthermal pulmonary vein ablation along with elution of an antifibrotic agent intended to eliminate arrhythmogenic substrate without the risk of stenosis and have demonstrated its functionality in 4 acute canine experiments. Further optimization of this device may provide an innovative means to simultaneously ablate and prevent pulmonary vein stenosis for improved AF treatment in humans. PMID:25092516

  19. Improved vascular healing after the successful treatment of very late sirolimus-eluting stent thrombosis with a bare metal stent implantation - A serial optical coherence tomography study.

    PubMed

    Bouki, Konstantina P; Vlad, Delia; Riga, Maria; Stergiouli, Ifigenia; Toutouzas, Konstantinos P

    2016-01-01

    We present the case of a patient with non-ST-elevated myocardial infarction due to very late stent thrombosis 2 years after a sirolimus-eluting stent implantation (SES). Optical coherence tomography (OCT) imaging identified vessel wall destruction of the whole stented coronary segment with multiple cavity formations along the entire stent length, severe strut malapposition and thrombi. The patient was treated successfully with the implantation of a bare metal stent (BMS). Follow-up OCT imaging at 12 months revealed the improvement of vascular healing with complete re-endothelialization of the distal parts of the new BMS, while the stent body remained partly uncovered, suggesting vascular toxicity due to the old SES. PMID:27445030

  20. Separation of nine compounds from Salvia plebeia R.Br. using two-step high-speed counter-current chromatography with different elution modes.

    PubMed

    Ren, Da-Bing; Qin, Yan-Hua; Yun, Yong-Huan; Lu, Hong-Mei; Chen, Xiao-Qing; Liang, Yi-Zeng

    2014-08-01

    Nine compounds were successfully separated from Salvia plebeia R.Br. using two-step high-speed counter-current chromatography with three elution modes. Elution-extrusion counter-current chromatography was applied in the first step, while classical counter-current chromatography and recycling counter-current chromatography were used in the second step. Three solvent systems, n-hexane/ethyl acetate/ethanol/water (4:6.5:3:7, v/v), methyl tert-butyl ether/ethyl acetate/n-butanol/methanol/water (6:4:1:2:8, v/v) and n-hexane/ethyl acetate/methanol/water (5:5.5:5:5, v/v) were screened and optimized for the two-step separation. The separation yielded nine compounds, including caffeic acid (1), 6-hydroxyluteuolin-7-glucoside (2), 5,7,3',4'-tetrahydroxy-6-methoxyflavanone-7-glucoside (3), nepitrin (4), rosmarinic acid (5), homoplantaginin (6), nepetin (7), hispidulin (8), and 5,6,7,4'-tertrahydroxyflavone (9). To the best of our knowledge, 5,7,3',4'-tetrahydroxy-6-methoxyflavanone-7-glucoside and 5,6,7,4'-tertrahydroxyflavone have been separated from Salvia plebeia R.Br. for the first time. The purities and structures of these compounds were identified by high-performance liquid chromatography, electrospray ionization mass spectrometry, (1)H and (13)C NMR spectroscopy. This study demonstrates that high-speed counter-current chromatography is a useful and flexible tool for the separation of components from a complex sample.

  1. Fast Gradient Elution Reversed-Phase Liquid Chromatography with Diode-Array Detection as a High-throughput Screening Method for Drugs of Abuse II. Data Analysis

    PubMed Central

    Porter, Sarah E. G.; Stoll, Dwight R.; Paek, Changyub; Rutan, Sarah C.; Carr, Peter W.

    2009-01-01

    In Part I of this work, we developed a method for the detection of drugs of abuse in biological samples based on fast gradient elution liquid-chromatography coupled with diode array spectroscopic detection (LC-DAD). In this part of the work, we apply the chemometric method of target factor analysis (TFA) to the chromatograms. This algorithm identifies the target compounds present in chromatograms based on a spectral library, resolves nearly co-eluting components, and differentiates between drugs with similar spectra. The ability to resolve highly overlapped peaks using the spectral data afforded by the DAD is what distinguishes the present method from conventional library searching methods. Our library has a mean list length of 1.255 and a discriminating power of 0.997 when both retention index and spectral factors are considered. The algorithm compares a library of 47 different compounds of toxicological relevance to unknown samples and identifies which compounds are present based on spectral and retention index matching. The application of a corrected retention index for identification rather than raw retention times compensates for long-term and column-to-column retention time shifts and allows for the use of a single library of spectral and retention data. Training data sets were used to establish the search and identification parameters of the method. A validation data set of 70 chromatograms was used to calculate the sensitivity (correct identification of positives) and specificity (correct identification of negatives) of the method, which were found to be 92 % and 94% respectively. PMID:17070534

  2. Detection of human viruses in rivers of a densly-populated area in Germany using a virus adsorption elution method optimized for PCR analyses.

    PubMed

    Hamza, Ibrahim Ahmed; Jurzik, Lars; Stang, Alexander; Sure, Klaus; Uberla, Klaus; Wilhelm, Michael

    2009-06-01

    Transmission of viruses via surface water is a major public health concern. To determine the viral concentration in rivers of a densely-populated area in Germany, the virus adsorption elution (VIRADEL) method was optimized for downstream PCR applications. Using a high-salt alkaline phosphate buffer for elution, the median recovery efficiency from spiked 1l water samples ranged from 21.3% to 100% for JC polyomavirus, human adenovirus type 5, Echovirus 11, and norovirus genogroup I. Analyses of 41 water samples collected during the winter 2007/08 from the rivers Ruhr and Rhine yielded detection rates 97.5% for adenoviruses and human polyomavirus (JC, BK), and 90% for group A rotaviruses. Noroviruses genogroup II were detected in 31.7% of the samples and only one sample was positive for enteroviruses. Virus concentrations ranged from 9.4 to 2.3x10(4) gen.equ./l. However, the genome equivalents/liter determined for the RNA viruses and their detection frequency are only lower limits, since the concentration procedure leads to carry-over of inhibitors of the reverse transcription step. Sequence analyses of the PCR products revealed that the adenovirus and rotavirus PCRs used could cross-react with animal viruses from the respective virus families. These results suggest that detection of human polyomavirus genomes is the most sensitive and specific marker for contamination of surface water with viruses from human sewage. Although we could routinely detect nucleic acids of viral pathogens in river water by the PCR-optimized VIRADEL method, threshold levels of viral nucleic acids above which there is a risk of infection with viruses derived from human remain to be determined.

  3. High-performance liquid chromatography coupled to direct analysis in real time mass spectrometry: investigations on gradient elution and influence of complex matrices on signal intensities.

    PubMed

    Beissmann, Susanne; Buchberger, Wolfgang; Hertsens, Robert; Klampfl, Christian W

    2011-08-01

    Direct analysis in real time (DART) time-of-flight mass spectrometry (TOF-MS) has been tested for its suitability as a detector for gradient elution HPLC. Thereby a strong dependency of signal intensity on the amount of organic solvent present in the eluent could be observed. Adding a make-up liquid (iso-propanol) post-column to the HPLC effluent greatly enhanced detection limits for early eluting compounds. Limits of detection achieved employing this approach were in the range of 7-27 μg L(-1) for the parabene test mixture and 15-87 μg L(-1) for the pharmaceuticals. In further investigations DART ionization was compared to several other widely used atmospheric pressure ionization methods with respect to signal suppression phenomena occurring in when samples with problematic matrices are analyzed. For this purpose extracts from environmental and waste water samples were selected as model matrices which were subsequently spiked with a set of six substances commonly present in personal care products as well as six pharmaceuticals at concentration levels between 100 μg L(-1) and 500 μg L(-1) corresponding to 100 ng L(-1) and 500 ng L(-1) respectively in the original sample. With ionization suppression of less than 11% for most analytes investigated, DART ionization showed similar to even somewhat superior behavior compared to atmospheric pressure chemical ionization (APCI) and atmospheric pressure photo ionization (APPI) for the Danube river water extract; for the more challenging matrix of the sewage plant effluent extract DART provided better results with ion suppression being less than 11% for 9 out of 12 analytes while values for APCI were lying between 20% and >90%. Electrospray ionization (ESI) was much more affected by suppression effects than DART with values between 26% and 80% for Danube river water; in combination with the sewage plant effluent matrix suppression >50% was observed for all analytes.

  4. Twelve-Month Results From the MAJESTIC Trial of the Eluvia Paclitaxel-Eluting Stent for Treatment of Obstructive Femoropopliteal Disease

    PubMed Central

    Müller-Hülsbeck, Stefan; Keirse, Koen; Zeller, Thomas; Schroë, Herman; Diaz-Cartelle, Juan

    2016-01-01

    Purpose: To report the 12-month results of the MAJESTIC clinical study of the self-expanding Eluvia paclitaxel-eluting stent in the treatment of femoropopliteal lesions. Methods: The prospective, single-arm, multicenter trial (clinicaltrials.gov identifier NCT01820637) enrolled 57 patients (mean age 69±9 years; 47 men) with chronic lower limb ischemia referable to de novo or restenotic lesions in the native superficial femoral and/or proximal popliteal arteries. A third of the patients had diabetes. Mean lesion length was 70.8±28.1 mm, and diameter stenosis was 86.3%±16.2%; 26 (46%) lesions were occluded. Primary patency was defined as duplex ultrasound peak systolic velocity ratio ≤2.5 and the absence of target lesion revascularization (TLR) or bypass. Major adverse events (MAEs) included all-cause death through 1 month and target limb major amputation and TLR through 12 months. Results: All 57 patients had a single Eluvia stent implanted, employing pre- and postdilation in 93% (53/57) and 95% (54/57) of cases, respectively. Technical success was 97% (55/57; 2 failures due to residual stenosis >30%). At 12 months, primary patency was 96% (49/51) and the MAE rate was 4% (2/53); both MAEs were TLRs. No stent fractures were identified. There were no major amputations. One death occurred 368 days postprocedure, unrelated to the device or procedure. Improvements in the Rutherford category were sustained through 1 year, with 81% (43/53) exhibiting no symptoms (category 0) and 13% (7/53) presenting with mild claudication (category 1). Mean ABI improved from 0.73±0.22 at baseline to 1.02±0.20 at 12 months. Conclusion: MAJESTIC results showed that patients whose femoropopliteal arteries were treated with the Eluvia drug-eluting stent sustained high patency and low MAE rates through 12 months. PMID:27193308

  5. Contrast-Enhanced Ultrasonography of Hepatocellular Carcinoma After Chemoembolisation Using Drug-Eluting Beads: A Pilot Study Focused on Sustained Tumor Necrosis

    SciTech Connect

    Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina Georgiou; Kornezos, Ioannis Matsaidonis, Dimitrios

    2010-10-15

    The purpose of this study was to assess the use of contrast-enhanced ultrasonography (CEUS) and the sustained antitumor effect of drug-eluting beads used for transarterial chemoembolisation (TACE) of unresectable hepatocellular carcinoma (HCC). Ten patients with solitary, unresectable HCC underwent CEUS before, 2 days after, and 35 to 40 days after TACE using a standard dose (4 ml) of drug-eluting beads (DC Beads; Biocompatibles, Surrey, UK) preloaded with doxorubicin (25 mg doxorubicin/ml hydrated beads). For CEUS, a second-generation contrast agent (SonoVue, Bracco, Milan, Italy) and a low mechanical-index technique were used. A part of the tumor was characterized as necrotic if it showed complete lack of enhancement. The percentage of necrosis was calculated at the sonographic section that depicted the largest diameter of the tumor. Differences in the extent of early (2 days after TACE) and delayed (35 to 40 days after TACE) necrosis were quantitatively and subjectively assessed. Early post-TACE tumor necrosis ranged from 21% to 70% (mean 43.5% {+-} 19%). There was a statistically significant (p = 0.0012, paired Student t test) higher percentage of delayed tumor necrosis, which ranged from 24% to 88% (mean 52.3% {+-} 20.3%). Subjective evaluation showed a delayed obvious increase of the necrotic areas in 5 patients. In 2 patients, tumor vessels that initially remained patent disappeared on the delayed follow-up. A part of tumor necrosis after chemoembolisation of HCC with DEB seems to take place later than 2 days after TACE. CEUS may provide evidence for the sustained antitumor effect of DEB-TACE. Nevertheless, the ideal time for the imaging evaluation of tumor response remains to be defined.

  6. Bioinspired Titanium Drug Eluting Platforms Based on a Poly-β-cyclodextrin-Chitosan Layer-by-Layer Self-Assembly Targeting Infections.

    PubMed

    Pérez-Anes, Alexandra; Gargouri, Myriem; Laure, William; Van Den Berghe, Hélène; Courcot, Elisabeth; Sobocinski, Jonathan; Tabary, Nicolas; Chai, Feng; Blach, Jean-François; Addad, Ahmed; Woisel, Patrice; Douroumis, Dennis; Martel, Bernard; Blanchemain, Nicolas; Lyskawa, Joël

    2015-06-17

    In the field of implantable titanium-based biomaterials, infections and inflammations are the most common forms of postoperative complications. The controlled local delivery of therapeutics from implants through polyelectrolyte multilayers (PEMs) has recently emerged as a versatile technique that has shown great promise in the transformation of a classical medical implant into a drug delivery system. Herein, we report the design and the elaboration of new biodegradable multidrug-eluting titanium platforms based on a polyelectrolyte multilayer bioactive coating that target infections. These systems were built up in mild conditions according to the layer-by-layer (L-b-L) assembly and incorporate two biocompatible polysaccharides held together through electrostatic interactions. A synthetic, negatively charged β-cyclodextrin-based polymer (PCD), well-known for forming stable and reversible complexes with hydrophobic therapeutic agents, was exploited as a multidrug reservoir, and chitosan (CHT), a naturally occurring, positively charged polyelectrolyte, was used as a barrier for controlling the drug delivery rate. These polyelectrolyte multilayer films were strongly attached to the titanium surface through a bioinspired polydopamine (PDA) film acting as an adhesive first layer and promoting the robust anchorage of PEMs onto the biomaterials. Prior to the multilayer film deposition, the interactions between both oppositely charged polyelectrolytes, as well the multilayer growth, were monitored by employing surface plasmon resonance (SPR). Several PEMs integrating 5, 10, and 15 bilayers were engineered using the dip coating strategy, and the polyelectrolyte surface densities were estimated by colorimetric titrations and gravimetric analyses. The morphologies of these multilayer systems, as well as their naturally occurring degradation in a physiological medium, were investigated by scanning electron microscopy (SEM), and their thicknesses were measured by means of

  7. Influence of second- and third-degree heart block on 30-day outcome following acute myocardial infarction in the drug-eluting stent era.

    PubMed

    Kim, Hack-Lyoung; Kim, Sang-Hyun; Seo, Jae-Bin; Chung, Woo-Young; Zo, Joo-Hee; Kim, Myung-A; Park, Kyung-Woo; Koo, Bon-Kwon; Kim, Hyo-Soo; Chae, In-Ho; Choi, Dong-Ju; Cho, Myeong-Chan; Kim, Young-Jo; Kim, Ju Han; Ahn, Youngkeun; Jeong, Myung Ho

    2014-12-01

    This study was conducted to investigate the prognostic value of heart block among patients with acute myocardial infarction (AMI) treated with drug-eluting stents. A total of 13,862 patients with AMI, registered in the nation-wide AMI database from January 2005 to June 2013, were analyzed. Second- (Mobitz type I or II) and third-degree atrioventricular block were considered as heart block in this study. Thirty-day major adverse cardiac events (MACE) including all causes of death, recurrent myocardial infarction, and revascularization were evaluated. Percutaneous coronary intervention with implantation of drug-eluting stent was performed in 89.8% of the patients. Heart block occurred in 378 patients (2.7%). Thirty-day MACE occurred in 1,144 patients (8.2%). Patients with heart block showed worse clinical parameters at initial admission, and the presence of heart block was associated with 30-day MACE in univariate analyses. However, the prognostic impact of heart block was not significant after adjustment of potential confounders (p = 0.489). Among patients with heart block, patients with a culprit in the left anterior descending (LAD) coronary artery had worse clinical outcomes than those of patients with a culprit in the left circumflex or right coronary artery. LAD culprit was a significant risk factor for 30-day MACE even after controlling for confounders (odds ratio 5.28, 95% confidence interval 1.22 to 22.81, p = 0.026). In conclusion, despite differences in clinical parameters at the initial admission, heart block was not an independent risk factor for 30-day MACE in adjusted analyses. However, a LAD culprit was an independent risk factor for 30-day MACE among patients with heart block.

  8. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials

    PubMed Central

    Andreotti, Felicita; Schulze, Volker; Kołodziejczak, Michalina; Buffon, Antonino; Brouwer, Marc; Costa, Francesco; Kowalewski, Mariusz; Parati, Gianfranco; Lip, Gregory Y H; Kelm, Malte; Valgimigli, Marco

    2015-01-01

    Objective To assess the benefits and risks of short term (<12 months) or extended (>12 months) dual antiplatelet therapy (DAPT) versus standard 12 month therapy, following percutaneous coronary intervention with drug eluting stents. Design Meta-analysis of randomised controlled trials. Data sources PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Cochrane Library, and major congress proceedings, searched from 1 January 2002 to 16 February 2015. Review methods Trials comparing short term (<12 months) or extended (>12 months) DAPT regimens with standard 12 month duration of therapy. Primary outcomes were cardiovascular mortality, myocardial infarction, stent thrombosis, major bleeding, and all cause mortality. Results 10 randomised controlled trials (n=32 287) were included. Compared to 12 month DAPT, a short term course of therapy was associated with a significant reduction in major bleeding (odds ratio 0.58 (95% confidence interval 0.36 to 0.92); P=0.02) with no significant differences in ischaemic or thrombotic outcomes. Extended versus 12 month DAPT yielded a significant reduction in the odds of myocardial infarction (0.53 (0.42 to 0.66); P<0.001) and stent thrombosis (0.33 (0.21 to 0.51); P<0.001), but more major bleeding (1.62 (1.26 to 2.09); P<0.001). All cause but not cardiovascular death was also significantly increased (1.30 (1.02 to 1.66); P=0.03). Conclusions Compared with a standard 12 month duration, short term DAPT (<12 months) after drug eluting stent implementation yields reduced bleeding with no apparent increase in ischaemic complications, and could be considered for most patients. In selected patients with low bleeding risk and very high ischaemic risk, extended DAPT (>12 months) could be considered. The increase in all cause but not cardiovascular death with extended DAPT requires further investigation. PMID:25883067

  9. Extent and persistence of streptozotocin-induced DNA damage and cell proliferation in rat kidney as determined by in vivo alkaline elution and BrdUrd labeling assays.

    PubMed

    Kraynak, A R; Storer, R D; Jensen, R D; Kloss, M W; Soper, K A; Clair, J H; DeLuca, J G; Nichols, W W; Eydelloth, R S

    1995-12-01

    The extent of DNA damage and cellular proliferation induced in rat kidneys by single doses of the diabetogenic alkylating agent streptozotocin (STZ) and the time course of repair of that damage were evaluated using an in vivo alkaline elution assay for DNA strand breaks and a bromodeoxyuridine (BrdUrd) labeling assay for cell replication. Male Sprague-Dawley rats were given iv injections of 0.25 to 60 mg/kg STZ and kidneys were harvested 3 hr later for alkaline elution. A dose of 2.5 mg/kg STZ was the lowest dose to induce detectable DNA strand breaks and extensive damage was produced by the commonly used diabetogenic dose of 60 mg/kg. To characterize the repair of the drug-induced DNA damage, kidneys were harvested from a 60 mg/kg group of animals 3 hr to 27 days after dosing. BrdUrd-labeled kidney sections were also evaluated to assess any cellular proliferative response associated with STZ administration. Significant DNA damage was detected up to 14 days after dosing with return to near background levels by 20 days. Similarly, treatment with 60 mg/kg STZ was associated with increases in BrdUrd labeling indices 4 and 9 days after treatment with resolution by 27 days. These results indicate that the cellular and molecular repair responses to a single diabetogenic dose of STZ are prolonged, requiring up to 3 weeks to complete. Thus, to avoid potential additive or synergistic effects on STZ-induced nephrotoxicity and/or genotoxicity, a delay in the start of experimental therapies in this model (other than insulin) s