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Sample records for isocratic elution utilizing

  1. Gradient x Isocratic Elution CCC on the Isolation of Verbascoside and Other Phenylethanoids: Influence of the Complexity of the Matrix.

    PubMed

    Leitão, Gilda Guimarães; Pinto, Shaft Correa; de Oliveira, Danilo Ribeiro; Timoteo, Patrícia; Guimarães, Michelle Guedes; Cordova, Wilmer H Perera; Leitão, Suzana Guimarães

    2015-11-01

    Verbascoside is a phenylethanoid glycoside widely distributed in nature, especially among the order Lamiales, occurring in numerous plants that are constituents of folk medicine preparations. This natural compound, previously isolated by our group from the ethyl acetate extract of Lantana trifolia using the gradient approach in countercurrent chromatography, was now isolated from the butanol extract of the same plant and from Lippia alba f. intermedia (Verbenaceae) using countercurrent chromatography in either gradient or isocratic elution modes. The ethyl acetate extract of L. alba, rich in phenylethanoids and flavonoids, was fractionated using countercurrent chromatography in the step-gradient elution approach. The four-step solvent system was composed of n-hexane-ethyl acetate-n-butanol-water (4 : 10 : X : 10), where X = 1 (solvent system A), 3 (solvent system B), 5 (solvent system C), and 7 (solvent system D), and allowed for the isolation of verbascoside along with other phenylethanoids and flavonoids from both plants. Verbascoside and 2'-O-β-apiosylverbascoside were further isolated from the n-butanol extract of L. trifolia using the solvent system ethyl acetate-n-butanol-water 10 : 2 : 10 on an isocratic run. The difference in the complexity of the two plant extracts demanded different purification steps, which included a second high-speed countercurrent chromatography purification using the isocratic elution mode. Georg Thieme Verlag KG Stuttgart · New York.

  2. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Isocratic and gradient elution in micellar liquid chromatography with Brij-35.

    PubMed

    Peris-García, Ester; Ortiz-Bolsico, Casandra; Baeza-Baeza, Juan José; García-Alvarez-Coque, María Celia

    2015-06-01

    Polyoxyethylene(23)lauryl ether (known as Brij-35) is a nonionic surfactant, which has been considered as an alternative to the extensively used in micellar liquid chromatography anionic surfactant sodium lauryl (dodecyl) sulfate, for the analysis of drugs and other types of compounds. Brij-35 is the most suitable nonionic surfactant for micellar liquid chromatography, owing to its commercial availability, low cost, low toxicity, high cloud temperature, and low background absorbance. However, it has had minor use. In this work, we gather and discuss some results obtained in our laboratory with several β-blockers, sulfonamides, and flavonoids, concerning the use of Brij-35 as mobile phase modifier in the isocratic and gradient modes. The chromatographic performance for purely micellar eluents (with only surfactant) and hybrid eluents (with surfactant and acetonitrile) is compared. Brij-35 increases the polarity of the alkyl-bonded stationary phase and its polyoxyethylene chain with the hydroxyl end group allows hydrogen-bond interactions, especially for phenolic compounds. This offers the possibility of using aqueous solutions of Brij-35 as mobile phases with sufficiently short retention times. The use of gradients of acetonitrile to keep the concentration of Brij-35 constant is another interesting strategy that yields a significant reduction in the peak widths, which guarantee high resolution.

  4. A Binary-Like Approach for the Computer Assisted Method Development of Isocratic and Programmed Ternary Solvent Elutions in Reversed-Phase Liquid Chromatography

    PubMed Central

    García-Lavandeira, J.; Martinez-Pontevedra, J.A.; Cela, R.

    2012-01-01

    A specific tool to enable exploration of multisolvent isocratic and programmed elutions for the computer assisted method development of reversed-phase liquid chromatography separations is described. The tool is purposely identical to those used in the optimization of binary solvent systems, which are by far the most commonly used by chromatographers. Existing data from failed binary solvent optimization processes are reused to explore ternary solvent systems with a few additional isocratic and programmed runs. This allows the development of efficient retention models for ternary systems, although the work of the chromatographer remains identical to that for optimization of binary systems. The retention models are used to develop an unattended optimization process and finally, the chromatographer selects the most satisfactory solution for testing and implementing in routine analysis. The process is exemplified with a mixture of 12 compounds that cannot be separated satisfactorily in aqueous binary solvent systems with methanol and acetonitrile as modifiers. PMID:22291054

  5. Alternating isocratic and step gradient elution high-speed counter-current chromatography for the isolation of minor phenolics from Ormocarpum kirkii bark.

    PubMed

    Kamto, Eutrophe Le Doux; Carvalho, Tatiane S C; Mbing, Joséphine Ngo; Matene, Marie C N; Pegnyemb, Dieudonné E; Leitão, Gilda G

    2017-01-13

    A total of 14 compounds were isolated from the ethanol bark extract of O. kirkii S. Moore (Fabaceae) by alternating isocratic and step gradient elution high-speed counter-current chromatography (HSCCC) methods, using several solvent systems with reference to the polarity of compounds being purified. The extract was successively fractionated with generic solvent systems including n-hexane-ethanol-water (4:2:2) and ethyl acetate-water (1:1). Resulting fractions were further purified using the following preparative gradient elution consisting of ethyl acetate-n-butanol-water (X:Y:10), (X:Y=9:1 (I); 8:2 (II); 7:3 (III); 6:4 (IV); 5:5 (V); 4:6 (VI) 3:7 (VII) and n-hexane- ethyl acetate-methanol-water (1:X:1:1), X=1, 2, 2.5, 3 solvent systems. Two flavone glycosides, apigenin-6-C-β-d-glucopyranosyl-4'-O-[β-d-glucopyranosyl-(1→5)]-β-d-apiofuranoside (1) and apigenin-6-C-β-d-glucopyranosyl-4'-O-β-d-apiofuranoside (2), and one biflavanone diglycoside 7,7″-di-O-β-d-glucosylliquiritigeninyl-(I-3,II-3)-naringenin (4) were isolated as new compounds along with other 11 known ones. The structures of the isolated compounds were identified by HPLC-UV, ESI-MS, 1D and 2D NMR and comparison with literature data. Thus, over common traditional chromatographic methods, the present study shows that HSCCC is a useful and fast method for natural product research with no losses and lower solvent use.

  6. Application of Snyder-Dolan Classification Scheme to the Selection of “Orthogonal” Columns for Fast Screening for Illicit Drugs and Impurity Profiling of Pharmaceuticals - I. Isocratic Elution

    PubMed Central

    Fan, Wenzhe; Zhang, Yu; Carr, Peter W.; Rutan, Sarah C.; Dumarey, Melanie; Schellinger, Adam P.; Pritts, Wayne

    2011-01-01

    Fourteen judiciously selected reversed-phase columns were tested with 18 cationic drug solutes under the isocratic elution conditions advised in the Snyder-Dolan (S-D) hydrophobic subtraction method of column classification. The standard errors (S.E.) of the least squares regressions of log k′ vs. log k′REF were obtained for a given column against a reference column and used to compare and classify columns based on their selectivity. The results are consistent with those obtained with a study of the 16 test solutes recommended by Snyder and Dolan. To the extent that these drugs are representative these results show that the S-D classification scheme is also generally applicable to pharmaceuticals under isocratic conditions. That is, those columns judged to be similar based on the S-D 16 solutes were similar based on the 18 drugs; furthermore those columns judged to have significantly different selectivities based on the 16 S-D probes appeared to be quite different for the drugs as well. Given that the S-D method has been used to classify more than 400 different types of reversed phases the extension to cationic drugs is a significant finding. PMID:19698948

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

    PubMed Central

    Norbeck, Angela D.; Monroe, Matthew E.; Adkins, Joshua N.; Smith, Richard D.

    2007-01-01

    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 LC-MS/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 measurements are required. However, the majority of proteins should be uniquely identifiable by using LC-MS with mass accuracies within +/− 1 ppm and elution time measurements within +/− 0.01 NET. PMID:15979333

  8. Predicting the behaviour of polydisperse polymers in liquid chromatography under isocratic and gradient conditions.

    PubMed

    Schoenmakers, Peter; Fitzpatrick, Fiona; Grothey, Ricarda

    2002-08-02

    In this paper we describe how the existing theories to describe retention and peak width in isocratic and gradient-elution liquid chromatography can be expanded to describe the retention behaviour of natural and synthetic repetitive polymers, which feature distributions of molecules with different masses (and often different structures) rather than unambiguous molecular formulas. For polydisperse samples, it is vital that the model accommodates (isocratic) elution of sample components before the onset of a gradient, elution during the gradient, and elution after the completion of the gradient. The expanded models can readily be implemented in standard spreadsheet software, such as Excel. We have created such spreadsheets based on the conventional model for retention in reversed-phase liquid chromatography (RPLC) and on two different models for retention in normal-phase liquid chromatography. The implementation allows an easy visualization of the theoretical concept. Up to three different polymeric series can be entered, with a total of up to 100 peaks being computed and displayed in isocratic or gradient-elution chromatograms. Also visualized are "retention models" (diagrams of isocratic retention vs. composition) and "calibration curves" (retention or elution composition vs. molecular mass or degree of polymerization). The coefficients in the isocratic retention model may be correlated, as has often been observed in RPLC. It is shown that under certain conditions such a correlation corresponds to the existence of so-called critical (isocratic) conditions, at which all the members of a given polymeric series (same composition and end groups, different number of repeat units) show co-elution.

  9. 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.

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

    PubMed

    Pfister, David; Morbidelli, Massimo

    2015-01-02

    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.

  11. Zotarolimus-eluting stent utilization in small-vessel coronary artery disease (ZEUS).

    PubMed

    Jim, Man-Hong; Yiu, Kai-Hang; Fung, Raymond Chi-Yan; Ho, Hee-Hwa; Ng, Andrew Kei-Yan; Siu, Chung-Wah; Chow, Wing-Hing

    2014-01-01

    The role of the second-generation zotarolimus-eluting stent RESOLUTE in small-vessel coronary artery disease is unclear. The aim of this study was examine the angiographic results of RESOLUTE in de novo coronary lesions of ≥50 % diameter stenosis in target vessels ≤2.5 mm. From August 2008 to April 2010, 142 symptomatic patients with 159 lesions who fitted the inclusion criteria were treated with RESOLUTE. The mean age of patients was 66 ± 10 years, with male predominance (66 %). Diabetes mellitus was found in 62 (43.7 %) patients, whereas multivessel disease was observed in 105 (73.9 %). The mean stent size and length used were 2.33 ± 0.13 and 22 ± 8 mm, respectively. Follow-up angiography was performed on 143 (89.9 %) lesions in 127 (89.4 %) patients at a mean of 10.3 ± 3.6 months. Angiographic restenosis was found in 9 (6.3 %) lesions; the late loss was 0.26 ± 0.34 mm. At 1-year follow-up there were four cardiovascular deaths, two nonfatal myocardial infarctions, and six repeated revascularizations. The resultant major adverse cardiac event rate was 8.5 %. The use of RESOLUTE to treat small-vessel disease is associated with good clinical and angiographic outcomes at 1 year.

  12. Impact of hospital and sociodemographic factors on utilization of drug-eluting stents in 2011–2012 Medicare cohort

    PubMed Central

    Tuliani, Tushar A.; Shenoy, Maithili; Parikh, Milind; Cohen, Mauricio G.; Grines, Cindy; Jutzy, Kenneth; Hilliard, Anthony

    2017-01-01

    Objective: Insurance status is a predictor of drug-eluting stent (DES) usage. Our study sought to determine the effect of hospital and sociodemographic characteristics on utilization of DES in nationwide inpatient discharges with uniform insurance (Medicare). Methods: We linked data from the 2011 to 2012 Medicare discharges, 2011 Medicare hospital referral region (HRR) report (racial composition of each HRR), American Hospital Association (number of beds, rural/urban location, public/private status, and academic affiliation of hospitals), and American Community Survey 2011 (median income using zip code). We analyzed diagnosis-related group (DRG) codes 249 (bare metal stent without complications), 246, and 247 (DES with and without complications, respectively). Univariate and multivariable logistic regression was conducted to determine odds ratios (OR) for utilization of DES. Results: There were 322,002 discharges with DRG codes 246 (54,279), 247 (209,365), and 249 (58,358) in our database. Higher odds of DES usage was observed in Hispanic dominant HRR(s) (OR: 1.37, 95% confidence interval [CI]: 1.33–1.42, P < 0.001) compared to Caucasian dominant HRR(s). DES utilization was similar in African-American and Caucasian dominant HRR (s). Higher odds of DES use was observed in median household income groups ≥$20,001 (OR: 1.07, 95% CI: 1.01–1.13, P - 0.03). Lower DES usage was observed in hospitals with higher total stent volume (quartile 4 vs. quartile 1: OR: 0.66, 95% CI: 0.63–0.69, P < 0.001) and for-profit hospitals (OR: 0.88, 95% CI: 0.85–0.92, P < 0.001). Conclusions: Our study findings suggest that there are significant differences in DES utilization in a national cohort of individuals with uniform insurance. PMID:28182024

  13. Refractive Index-Based Detection of Gradient Elution Liquid Chromatography using Chip-Integrated Microring Resonator Arrays

    PubMed Central

    Wade, James H.; Bailey, Ryan C.

    2014-01-01

    Refractive index-based sensors offer attractive characteristics as non-destructive and universal detectors for liquid chromatographic separations, but a small dynamic range and sensitivity to minor thermal perturbations limit the utility of commercial RI detectors for many potential applications, especially those requiring the use of gradient elutions. As such, RI detectors find use almost exclusively in sample abundant, isocratic separations when interfaced with HPLC. Silicon photonic microring resonators are refractive index-sensitive optical devices that feature good sensitivity and tremendous dynamic range. The large dynamic range of microring resonators allows the sensors to function across a wide spectrum of refractive indices, such as that encountered when moving from an aqueous to organic mobile phase during a gradient elution – a key analytical advantage not supported in commercial RI detectors. Microrings are easily configured into sensor arrays, and chip-integrated control microrings enable real-time corrections of thermal drift. Thermal controls allow for analyses at any temperature and in the absence of rigorous temperature control, obviating extended detector equilibration wait times. Herein, proof of concept isocratic and gradient elution separations were performed using well characterized model analytes (e.g., caffeine, ibuprofen) in both neat buffer and more complex sample matrices. These experiments demonstrate the ability of microring arrays to perform isocratic and gradient elutions under ambient conditions, avoiding two major limitations of commercial RI-based detectors and maintaining comparable bulk RI sensitivity. Further benefit may be realized in the future through selective surface functionalization to impart degrees of post-column (bio)molecular specificity at the detection phase of a separation. The chip-based and microscale nature of microring resonators also makes it an attractive potential detection technology that could be

  14. Development and Validation of a Simple Isocratic HPLC Method for Simultaneous Estimation of Phytosterols in Cissus quadrangularis.

    PubMed

    Shah, Unnati M; Patel, S M; Patel, P H; Hingorani, L; Jadhav, R B

    2010-11-01

    Cissus quadrangularis L. is a promising remedy prescribed in the ancient Ayurvedic literature for bone fracture healing properties. As this activity has been extensively investigated and well established, a range of formulations containing C. quadrangularis has been marketed. This work reports the development and validation of a reliable RP-HPLC method for the analysis of phytosterols in the various extracts of the plant. The proposed method utilizes a Cosmosil C(8) column (250 ΄ 4.6 mm) with a compatible Phenomenex C(8) guard column with isocratic elution of acetonitrile and water (95:5 v/v) at 25°. An effluent flow rate of 2 ml/min and UV detection at 202 nm was used for the analysis of phytosterols. The described method was linear in the range of 1-500 μg/ml, with excellent correlation coefficients. The precision, robustness and ruggedness values were also within the prescribed limits (less than 2%). The recovery values were within the range, which indicates that the accuracy of the analysis was good and that the interference of the matrix with the recovery of phytosterols was low. The phytosterols were found to be stable in a stock solution for 48 h (% RSD was below 2%) and no interfering extra peaks were observed under controlled stress conditions. The proposed method is simple, specific, precise, accurate, and reproducible and thus can be used for routine analysis of C. quadrangularis phytosterols in quality control laboratories.

  15. Development and Validation of a Simple Isocratic HPLC Method for Simultaneous Estimation of Phytosterols in Cissus quadrangularis

    PubMed Central

    Shah, Unnati M.; Patel, S. M.; Patel, P. H.; Hingorani, L.; Jadhav, R. B.

    2010-01-01

    Cissus quadrangularis L. is a promising remedy prescribed in the ancient Ayurvedic literature for bone fracture healing properties. As this activity has been extensively investigated and well established, a range of formulations containing C. quadrangularis has been marketed. This work reports the development and validation of a reliable RP-HPLC method for the analysis of phytosterols in the various extracts of the plant. The proposed method utilizes a Cosmosil C8 column (250 ΄ 4.6 mm) with a compatible Phenomenex C8 guard column with isocratic elution of acetonitrile and water (95:5 v/v) at 25°. An effluent flow rate of 2 ml/min and UV detection at 202 nm was used for the analysis of phytosterols. The described method was linear in the range of 1–500 μg/ml, with excellent correlation coefficients. The precision, robustness and ruggedness values were also within the prescribed limits (less than 2%). The recovery values were within the range, which indicates that the accuracy of the analysis was good and that the interference of the matrix with the recovery of phytosterols was low. The phytosterols were found to be stable in a stock solution for 48 h (% RSD was below 2%) and no interfering extra peaks were observed under controlled stress conditions. The proposed method is simple, specific, precise, accurate, and reproducible and thus can be used for routine analysis of C. quadrangularis phytosterols in quality control laboratories. PMID:21969748

  16. 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.

  17. Combined paclitaxel-eluting balloon and Genous cobalt-chromium alloy stent utilization in de novo coronary stenoses (PEGASUS).

    PubMed

    Jim, Man-Hong; Fung, Raymond Chi-Yan; Yiu, Kai-Hang; Ng, Andrew Kei-Yan; Siu, Chung-Wah; Fan, Katherine Yu-Yan

    2013-12-01

    The aim of this study was to examine the angiographic result and its outcome predictors using the combination of paclitaxel-eluting balloon (PEB) and Genous stent. This approach to treat coronary stenoses is a logical strategy to strike a balance between minimizing restenosis and stent thrombosis. From November 2010 to June 2012, 40 symptomatic patients with 44 de novo coronary lesions of diameter stenosis ≥ 50% were treated with the combination of PEB and Genous stents. Angiographic and clinical follow-up were intended at 6 and 9 months, respectively. The mean age of patients was 61 ± 11 years, with male predominance (83%). Diabetes mellitus and end-stage renal failure on peritoneal dialysis were found in 15 (38%) and 10 (25%) patients, respectively. Patients received dual antiplatelet therapy for 5.1 ± 1.5 months post procedure. The size and length of PEB used was larger than the stents (3.13 ± 0.46 mm and 28 ± 9 mm vs. 2.98 ± 0.36 mm and 23 ± 7 mm). Restudy angiography was performed on 41 (95%) lesions in 37 (93%) patients at 5.9 ± 1.7 months. Angiographic restenosis was seen in 5 (12%) lesions, and significantly associated with diabetes mellitus and dialysis dependency; the late lumen loss was 0.38 ± 0.37 mm. At 9-month follow-up, no stent thrombosis was observed. The use of PEB combined with Genous stent is associated with a reasonably low restenosis and late lumen loss, whereas diabetes mellitus and renal failure with dialysis are poor predictors of angiographic restenosis. © 2013, Wiley Periodicals, Inc.

  18. 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).

  19. Direct injection isocratic high-performance liquid chromatographic analysis of mitomycin C in plasma.

    PubMed

    Song, D; Au, J L

    1996-02-09

    A direct injection high-performance liquid chromatography method is described for the determination of mitomycin C (MMC) in human plasma. The stationary phase consisted of hydrophilic and hydrophobic functional groups covalently bound to silicone-coated silica beads (CAPCELL PAK MF Ph-1, 150x4.6 mm I.D., 5 microns). A mobile phase using 100% water gave a better separation of MMC from endogenous interferences as compared to a mobile phase with 12.5% acetonitrile and 2.5 mM phosphate buffer (pH 6.9). Using water as the eluent (1 ml/min) and UV detection at 365 nm, MMC was found to elute at 5.0 min with a peak width of 0.3 min, whereas endogenous interferences eluted before 3 min. Total assay time per sample was 6 min. Internal standard was not required because the recovery of MMC was nearly complete, about 90% from 20 to 5000 ng/ml. The standard curve was linear from 20 to 5000 ng/ml in plasma, and the intra-and inter-day variation was between 3 to 6%. The lower detection limit was 5 ng/ml with a 25 microliters sample, which represents a two- to four-fold improvement over the 10 ng/ml detection limit by previous methods using liquid-liquid extraction and comparable sample size. The simplicity of this method, i.e., no sample extraction, no internal standard, 100% aqueous mobile phase, isocratic elution and short analysis time (6 min/sample), makes it suitable for large scale routine sample analysis, whereas its small sample volume requirement and high sensitivity are useful for pharmacokinetic studies in small animals where limited sample is available.

  20. 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.

  1. Two-Year outcomes after utilization of the TAXUS paclitaxel-eluting stent in bifurcations and multivessel stenting in the ARRIVE registries.

    PubMed

    Brilakis, Emmanouil S; Lasala, John M; Cox, David A; Bowman, Thomas S; Starzyk, Ruth M; Dawkins, Keith D

    2011-08-01

    Examine the incidence of clinical events after utilization of the TAXUS(®) Express(®) paclitaxel-eluting stent (PES) in multivessel and bifurcation coronary stenting in an unselected patient population. The ARRIVE Program compiled data on 7,492 patients receiving ≥1 TAXUS Express PES, including patients with multivessel stenting (MVS; n = 1,208) and bifurcation stenting (n = 575). Patients were enrolled at procedure start with no mandated inclusion/exclusion criteria; all cardiac events were monitored with independent adjudication of end-points. Compared to simple use (single vessel/single stent) patients undergoing native intervention (N = 2,698), MVS patients had significantly more baseline comorbidities. Both groups had higher 2-year rates of mortality (7.3%[MVS] and 7.5%[bifurcation] vs. 4.2%[simple-use], P < 0.001), myocardial infarction (5.5% and 4.6% vs. 2.2%, P < 0.001 and P = 0.002), target vessel revascularization (15.5% and 14.8% vs. 7.7%, P < 0.001), and Academic Research Consortium definite/probable stent thrombosis (4.3% and 4.4% vs. 1.4%, P < 0.001) than the simple-use group. ARRIVE multivessel and bifurcation stenting patients have significantly higher clinical risk through 2 years compared to simple-use patients. In the absence of large randomized controlled trials in these populations, ARRIVE provides important insight into clinical outcomes over an extended period of time. (J Interven Cardiol 2011;24:342-350). ©2011, Wiley Periodicals, Inc.

  2. Elution strategies for reversed-phase high-performance liquid chromatography analysis of sucrose alkanoate regioisomers with charged aerosol detection.

    PubMed

    Lie, Aleksander; Pedersen, Lars Haastrup

    2013-10-11

    A broad range of elution strategies for RP-HPLC analysis of sucrose alkanoate regioisomers with CAD was systematically evaluated. The HPLC analyses were investigated using design-of-experiments methodology and analysed by analysis of variance (ANOVA) and regression modelling. Isocratic elutions, isocratic elutions with increased flow, and gradient elutions with step-down profiles and step-up profiles were performed and the chromatographic parameters of the different elution strategies were described by suitable variables. Based on peak resolutions general resolution deviation for multiple peaks (RDm) was developed for sample-independent evaluation of separation of any number of peaks in chromatographic analysis. Isocratic elutions of sucrose alkanoates showed similar relationships between eluent acetonitrile concentration and retention time for all regioisomers of sucrose caprate and sucrose laurate, as confirmed by evaluation of the curvatures using approximate second derivatives and Kendall rank correlation coefficients. Regression modelling and statistical analysis showed that acetonitrile concentration and flow rate were highly significant for both average adjusted retention time and RDm for sucrose laurate. For both responses the effect of changes in acetonitrile concentration was larger than the effect of changes in flow rate, over the ranges studied. Regression modelling of the step-down gradient profiles for the sucrose alkanoates showed that the eluent acetonitrile concentrations were the overall most significant variables for retention time and separation. The models for average adjusted retention time of sucrose caprate and sucrose laurate showed only a few differences in the significance levels of terms, while the models for RDm showed larger differences between the sucrose alkanoates, in both the number of terms and their significance. Efficiency evaluation of elution strategies, in terms of RDm and analysis time, showed that the best results were

  3. Simultaneous isocratic separation of phenolic acids and flavonoids using micellar liquid chromatography.

    PubMed

    Hadjmohammadi, Mohammad Reza; Nazari, S Saman S J

    2013-12-01

    The simultaneous isocratic separation of a mixture of five phenolic acids and four flavonoids (two important groups of natural polyphenolic compounds with very different polarities) was investigated in three different RPLC modes using a hydro-organic mobile phase, and mobile phases containing SDS at concentrations below and above the critical micellar concentration (submicellar LC and micellar LC (MLC), respectively). In the hydro-organic mode, methanol and acetonitrile; in the submicellar mode methanol; and in the micellar mode, methanol and 1-propanol were examined individually as organic modifiers. Regarding the other modes, MLC provided more appropriate resolutions and analysis time and was preferred for the separation of the selected compounds. Optimization of separation in MLC was performed using an interpretative approach for each alcohol. In this way, the retention of phenolic acids and flavonoids were modeled using the retention factors obtained from five different mobile phases, then the Pareto optimality method was applied to find the best compatibility between analysis time and quality of separation. The results of this study showed some promising advantages of MLC for the simultaneous separation of phenolic acids and flavonoids, including low consumption of organic solvent, good resolution, short analysis time, and no requirement of gradient elution.

  4. 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.

  5. 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

  6. Column temperature as an active variable in the isocratic, normal-phase high-performance liquid chromatography separation of lipophilic metabolites of nonylphenol ethoxylates.

    PubMed

    Babay, Paola A; Gettar, Raquel T; Magallanes, Jorge F; Becquart, Elena T; Thiele, Björn; Batistoni, Daniel A

    2007-07-20

    Normal-phase separation of technical grade nonylphenol (t-NP, about 90% 4-nonylphenol), 4-nonylphenol mono-ethoxylate (4-NP1EO) and 4-nonylphenol di-ethoxylate (4-NP2EO) was assessed, with the inclusion of column temperature as an active variable. The compound 2,4,6-trimethylphenol was evaluated for use as internal standard. Isocratic elution with 2-propanol/hexanes mixtures from an amino-silica column and spectrometric UV detection at 277 nm were employed. Technical nonylphenol presented a significant contribution from unknown substances that eluted with retention times similar to that of 4-NP1EO. GC-MS analysis of the unknowns allowed to identify them as isomers of 2-NP. The response of the system to joint variations in flow rate, eluent composition and column temperature was investigated by means of Doehlert statistical experimental design. A model for retention of the analytes as a function of the experimental variables was proposed, and separation selectivity was studied. Selection of the optimal working zone was made through desirability function (D) calculations. Potential co-elution of 2-NP isomers with 4-NP1EO was considered when optimizing the separation. The occurrence of a restricted region of the experimental space where baseline resolution of analytes, associated impurities and internal standard results feasible (D not equal to 0) is apparent.

  7. Isocratic, simultaneous reversed-phase high-performance liquid chromatographic estimation of six drugs for combined hypertension therapy.

    PubMed

    Patel, Y P; Patil, S; Bhoir, I C; Sundaresan, M

    1998-12-18

    We report an isocratic, HPLC procedure for assay of the orally administered hypertension drugs [atenolol, amlodipine, nifedipine, nitrendipine, nimodipine and felodipine given in retention order] of which atenolol, an aryloxypropanolamine beta-blocker is administered with anyone of the other five dihydropyridine calcium channel blockers in combined hypertension therapy. The drugs were dissolved in methanol and 20 microliters of a mix of the drugs was injected onto a reverse phase JASCO-metaphase ODS (250 x 4.0 mm) 5 mu column. Any one of the six drugs could be used as the internal standard. The drugs were resolved by elution with a pH 4.5 equivolume mobile phase of acetonitrile-0.01 M KH2PO4, with pH adjustments done with H3PO4 (flow-rate 1.5 ml min-1). The column effluent was monitored at 250 nm. The detector response (peak height ratio) was linear in the dynamic range of 25-3200 ng ml-1 of these drugs, with the detection limits at approximately 15 ng ml-1. Full statistical evaluation of the data including linear regression (least-square fit) analysis was performed. The suggested procedure has the advantage that all the five dihydropyridine derivatives can be quantified alone or in formulation with atenolol.

  8. Quantification of amino acids in fermentation media by isocratic HPLC analysis of their α-hydroxy acid derivatives.

    PubMed

    Pleissner, Daniel; Wimmer, Reinhard; Eriksen, Niels T

    2011-01-01

    In this paper we describe a novel method for quantification of amino acids. First, α-hydroxy acid derivatives of amino acids were formed after reaction with dinitrogen trioxide by the van Slyke reaction. Second, the α-hydroxy acid derivatives were separated on an Aminex HPX-87H column (Bio-Rad) eluted isocratically with 5 mM H(2)SO(4) and quantified by refractive index detection. We were able to measure the reaction products of 13 of the 20 classical amino acids: glycine, l-alanine, l-valine, l-leucine, l-isoleucine, l-methionine, l-serine, l-threonine, l-asparagine, l-glutamine, l-aspartic acid, l-glutamic acid, and l-proline. We obtained linear relationships between the product peak areas and initial amino acid concentration, whereby the concentrations of these amino acids could be quantified on the basis of the quantification of their products. The method can be used to analyze amino acids in parallel with other small molecules, such as sugars or short chain fatty acids, and was used for parallel quantification of glycine, l-alanine, or l-glutamic acid, and glucose uptake in cultures of the heterotrophic dinoflagellate Crypthecodinium cohnii . The method can also be used to quantify other amines, as demonstrated by detection of Tris (2-amino-2-(hydroxymethyl)propane-1,3-diol).

  9. 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.

  10. Determination of carnosine and other biogenic imidazoles in equine plasma by isocratic reversed-phase ion-pair high-performance liquid chromatography.

    PubMed

    Dunnett, M; Harris, R C

    1992-08-07

    The isocratic reversed-phase ion-pair high-performance liquid chromatographic technique presented provides a sensitive, rapid and reproducible analytical method for the selective determination of carnosine and other biogenic imidazoles in equine plasma. Plasma was deproteinized with 5-sulphosalicylic acid and the compounds of interest were isolated by sorbent extraction on Bond Elut PRS cartridges. Recoveries were 97-105% and the lowest limits of detection were 58.3-80.1 nM. All compounds of interest were well resolved within a maximum retention time of 9.2 min. The mean equine plasma carnosine level determined by this method was 11.31 microM. Comparative determinations were made in canine and human plasma. Carnosine was not detected in human plasma. Concentrations of imidazole in canine plasma are reported here for the first time.

  11. 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.

  12. Bare metal stents, durable polymer drug eluting stents, and biodegradable polymer drug eluting stents for coronary artery disease: mixed treatment comparison meta-analysis

    PubMed Central

    Toklu, Bora; Amoroso, Nicholas; Fusaro, Mario; Kumar, Sunil; Hannan, Edward L; Faxon, David P; Feit, Frederick

    2013-01-01

    mortality compared with cobalt chromium everolimus eluting stents (1.52, 1.02 to 2.22). Overall, among all stent types, the newer generation durable polymer drug eluting stents (zotarolimus eluting stent-Resolute, cobalt chromium everolimus eluting stents, and platinum chromium everolimus eluting stents) were the most efficacious (lowest target vessel revascularization rate) stents, and cobalt chromium everolimus eluting stents were the safest with significant reductions in definite stent thrombosis (rate ratio 0.35, 0.21 to 0.53), myocardial infarction (0.65, 0.55 to 0.75), and death (0.72, 0.58 to 0.90) compared with bare metal stents. Conclusions Biodegradable polymer drug eluting stents are superior to first generation durable polymer drug eluting stents but not to newer generation durable polymer stents in reducing target vessel revascularization. Newer generation durable polymer stents, and especially cobalt chromium everolimus eluting stents, have the best combination of efficacy and safety. The utility of biodegradable polymer stents in the context of excellent clinical outcomes with newer generation durable polymer stents needs to be proven. PMID:24212107

  13. Bare metal stents, durable polymer drug eluting stents, and biodegradable polymer drug eluting stents for coronary artery disease: mixed treatment comparison meta-analysis.

    PubMed

    Bangalore, Sripal; Toklu, Bora; Amoroso, Nicholas; Fusaro, Mario; Kumar, Sunil; Hannan, Edward L; Faxon, David P; Feit, Frederick

    2013-11-08

    .02 to 2.22). Overall, among all stent types, the newer generation durable polymer drug eluting stents (zotarolimus eluting stent-Resolute, cobalt chromium everolimus eluting stents, and platinum chromium everolimus eluting stents) were the most efficacious (lowest target vessel revascularization rate) stents, and cobalt chromium everolimus eluting stents were the safest with significant reductions in definite stent thrombosis (rate ratio 0.35, 0.21 to 0.53), myocardial infarction (0.65, 0.55 to 0.75), and death (0.72, 0.58 to 0.90) compared with bare metal stents. Biodegradable polymer drug eluting stents are superior to first generation durable polymer drug eluting stents but not to newer generation durable polymer stents in reducing target vessel revascularization. Newer generation durable polymer stents, and especially cobalt chromium everolimus eluting stents, have the best combination of efficacy and safety. The utility of biodegradable polymer stents in the context of excellent clinical outcomes with newer generation durable polymer stents needs to be proven.

  14. Safety and efficacy of low-dose paclitaxel utilizing the cobra-P drug-eluting stent system with a novel biodegradable coating in de novo coronary lesions: the PLUS-ONE first-in-man study.

    PubMed

    Calderas, Carlos; Condado, Jose Francisco; Condado, Jose Antonio; Flores, Alejandra; Mueller, Amy; Thomas, Jack; Nakatani, Daisaku; Honda, Yasuhiro; Waseda, Katsuhisa; Fitzgerald, Peter

    2014-01-01

    The Cobra-P drug-eluting stent (DES) system consists of cobalt chromium alloy with bio-absorbable siloxane sol-gel matrix coating that elutes low dose paclitaxel within 6 months. The aim of this first-in-man trial was to evaluate the safety and performance of 2 doses of the Cobra-P DES. A total of 60 lesions (54 patients) were sequentially assigned to 2 different paclitaxel doses: group A (3.7 μg/18mm, n=30) or group B (8 μg/18mm, n=30). The primary endpoint was MACE at 4 months defined as cardiac death, myocardial infarction, and target lesion revascularization. Patient and lesion characteristics were matched between the 2 groups except for male sex. MACE at 4 months was 3.3% and 0% respectively (P=1.000) and at 1-year follow-up remained unchanged. In-stent late loss at 4 months was similar in both groups (0.36 ± 0.30mm and 0.34 ± 0.20mm P=.773). In this FIM study, implantation of the Cobra-P low dose paclitaxel-eluting stent with a bioabsorbable sol-gel coating was proven to be feasible and safe. Moderate neointimal proliferation was observed as well as an acceptable MACE rate up to 1 year. © 2014.

  15. Robust isocratic high performance liquid chromatographic method for simultaneous determination of seven antiepileptic drugs including lamotrigine, oxcarbazepine and zonisamide in serum after solid-phase extraction.

    PubMed

    Vermeij, T A C; Edelbroek, P M

    2007-09-15

    A rapid, simple and robust method is presented for the simultaneous determination of seven antiepileptic drugs (AEDs), including primidone, phenobarbital, phenytoin, carbamazepine with its two major metabolites carbamazepine-10,11-epoxide and carbamazepine-10,11-(trans)-dihydrodiol and the new AEDs lamotrigine, hydroxycarbazepine (active metabolite of oxcarbazepine) and zonisamide in serum by high performance liquid chromatography (HPLC)-diode array detector (DAD). After solid-phase extraction, separation is achieved on an Alltima 3C18 analytical column using isocratic elution with a mixture of acetonitrile, methanol and phosphate buffer at 45 degrees C. The method is exhaustively validated, including experimental design in combination with statistical evaluation (ANOVA) to study the robustness of chromatography and sample preparation. Commonly co-administered antiepileptic drugs do not interfere with the method. Intra-day precision (RSD<1.9%), linearity, lower limit of quantitation (LOQ<0.065 mg/l) and robustness make the method suitable for daily therapeutic drug monitoring and pharmacokinetic studies.

  16. Impact of normal-phase gradient elution in chiral chromatography: a novel, robust, efficient and rapid chiral screening procedure.

    PubMed

    de la Puente Luz, María; White, Craig T; Rivera-Sagredo, Alfonso; Reilly, John; Burton, Keith; Harvey, Georgina

    2003-01-03

    Novel normal-phase gradient systems have been employed for fast high-throughput chiral analyses of Discovery compounds in our research laboratories in Eli Lilly and Company. In this report, we describe an automated screening approach based on gradient elution, in order to achieve accurate enantiomeric excess determinations, and chiral separations when needed, in the shortest possible timeframe. Baseline resolution of enantiomers has been obtained for over 85% of the samples so tested. For the remaining cases, complete enantioseparation by isocratic optimisation is generally achieved in a single shot. This technique has been proven to be robust and is now standard operating procedure at our analytical research laboratories.

  17. HPLC thermodynamic study of new potential antiepileptic compounds on cholesterol column using isocratic elution with methanol/water and acetonitrile/water eluent systems.

    PubMed

    Flieger, Jolanta; Trębacz, Hanna; Pizoń, Magdalena; Kowalska, Anna; Szczęsna, Agnieszka; Plech, Tomasz

    2017-09-04

    Basic thermodynamic functions responsible for retention of new 1,2,4-triazole derivatives exhibiting varied antiepileptic activity on cholesterol-based stationary phase were determined. Evaluation of the Gibbs energy change, the change in enthalpy and the change in entropy was based on the van 't Hoff relationship representing ln k vs. 1/T. A detailed discussion of the van 't Hoff equation, exploring the influence of the phase ratio on deviations from linearity in a Van 't Hoff plot is presented. We show chromatographic evidence to the question of how a varied mobile phase composition may cause different thermodynamic phase ratios. The analysis of data from a differential scanning calorimetry excluded any phase transitions of either the individual solutes or cholesterol stationary phase suspended in the mobile phase components within the studied temperature range. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  18. Robust isocratic liquid chromatographic separation of functional poly(methyl methacrylate).

    PubMed

    Jiang, Xulin; Lima, Vincent; Schoenmakers, Peter J

    2003-11-07

    The separation of telechelic poly(methyl methacrylate) (PMMA) prepolymers based on the number of end-groups under critical liquid chromatography (LC) conditions has been studied using a bare-silica column, which can interact with polar functional groups. The critical solvent compositions for non-functional, mono-functional and bi-functional PMMAs were determined in normal-phase LC using mixtures of acetonitrile and dichloromethane (DCM) of varying composition as the mobile phase. The telechelic prepolymers were successfully separated according to hydroxyl (OH) functionality (with zero, one, or two OH groups, respectively) under the critical conditions, in which fast (5 min), base-line separations were obtained independent of molecular weight. Changing the column temperature, flow rate, and mobile-phase composition within a certain range did not affect the functionality separation. Therefore this isocratic LC separation method is quite robust. Evaporative light-scattering detector (ELSD) calibration curves were used for the quantitative analysis of functional PMMA prepolymers.

  19. Trapping multiple dual mode centrifugal partition chromatography for the separation of intermediately-eluting components: Operating parameter selection.

    PubMed

    Goll, Johannes; Morley, Raena; Minceva, Mirjana

    2017-05-05

    The preparative separation of intermediately-eluting components in liquid-liquid chromatography is commonly performed with isocratic batch injections, a technique which often leads to low yield and/or purity as a result of peak overlap. Two-column trapping multiple dual mode centrifugal partition chromatography, an alternative discontinuous method for the separation of a mixture into three product fractions (early-, intermediately-, and late-eluting components) at full recovery, is presented in this work. A mathematical shortcut method based on equilibrium theory assumptions is derived for the determination of the key operating parameters (i.e., step durations and number of steps). The feasibility of the technique and the accompanying short-cut method is demonstrated by proof-of-concept experiments for the separation of two paraben model mixtures. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Methodology for a rapid and simultaneous determination of total cysteine, homocysteine, cysteinylglycine and glutathione in plasma by isocratic RP-HPLC.

    PubMed

    Ferin, Rita; Pavão, Maria Leonor; Baptista, José

    2012-12-12

    Alterations in the plasma aminothiols levels can be considered as important biomarkers for the diagnosis and screening of several human disorders, namely cardiovascular diseases. We aimed to optimize a rapid, sensitive and accurate RP-HPLC methodology with fluorescence detection, for the simultaneous determination of the total concentrations of cysteine, homocysteine, cysteinylglycine and glutathione in blood plasma, as well as its application to the evaluation of those thiols levels in plasma of a group of Azorean subjects. Aminothiols were reduced with tri-n-butylphosphine and derivatized with a thiol-specific fluorogenic reagent ammonium 7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate. The thiols adducts were separated by an isocratic elution on a Platinum EPS C18 analytical column (53mm×7mm I.D., 3μm) using a phosphate buffer containing 4% of acetonitrile as a mobile phase. Results indicated an excellent linearity for all the analytes over their respective concentration ranges with correlation coefficients (r(2)) ≥0.99. The LOD for the four plasma thiols was lower than 0.10μmol/L, while LOQ varied from 0.5 to 15μmol/L. For both intra- and inter-day precision, the RSD (%) values were lower than 1.9%, and the CV (%) values were found under 0.5%. The recovery ranged from 92% to 100% indicating a high degree of the method's accuracy. This method allows a simultaneous, complete analysis of the four plasma aminothiols and the internal standard in 6min. By reducing the total run time, a larger number of analysis can be performed daily.

  1. Isocratic high-performance liquid chromatography-photodiode-array detection method for determination of lysine- and arginine-vasopressins and oxytocin in biological samples.

    PubMed

    Rao, P S; Weinstein, G S; Wilson, D W; Rujikarn, N; Tyras, D H

    1991-01-04

    A simple, isocratic, sensitive (1 ng), and specific high-performance liquid chromatographic (HPLC) method based on photodiode-array detection (PAD) is described for simultaneous quantitation of the bioactive peptides, lysine vasopressin (LVP), arginine vasopressin (AVP) and oxytocin (OXY). Acidified pig plasma and left ventricular (LV) tissue samples were first extracted with Sep-Pak C18 columns, and the bioactive peptides were eluted with methanol, then dried at 37 degrees C and reconstituted with HPLC mobile phase. The bioactive peptides were separated by HPLC on a Dynamax 3009-A C8 column with a mobile phase of 0.1% trichloroacetic acid-50 mM heptanesulfonic acid-30mM triethylamine-20% acetonitrile in water, pH 2.5 and identified with a Waters 990-PAD system (spectrum index plots in the range 200-400 nm). Standards of LVP, AVP and OXY and their mixtures showed a linear increase in the range 5 to 100 ng and were eluted at 6.1, 6.9 and 4.6 min, respectively. Spectrum analysis showed a distinct absorption peak at 280 nm, corresponding to peptide bonds. The reproducibility of the method coefficient of variation for standards is 6.9, 5.8 and 4.7% for LVP, AVP and OXY, respectively. In plasma and tissue it is much higher: 12.9% (LV tissue) and 18.6% (plasma) for LVP. Pig plasma contains negligible amounts of AVP and OXY; LVP is much higher (0.28 +/- 0.19 ng/ml). In pig tissue, LVP predominates (6.95 ng/g wet weight) compared to AVP (1.45) and OXY (1.50). Spectral analysis is necessary to identify the bioactive peptide peaks among interfering substances and to increase the sensitivity four-fold. The method described here is useful for the simultaneous determination of LVP, AVP and OXY in the nanogram range and can be extended to picogram levels by employing PAD spectral analysis techniques.

  2. Isocratic RP-HPLC method for rutin determination in solid oral dosage forms.

    PubMed

    Kuntić, Vesna; Pejić, Natasa; Ivković, Branka; Vujić, Zorica; Ilić, Katarina; Mićić, Svetlana; Vukojević, Vladana

    2007-01-17

    A rapid and sensitive assay for quantitative determination of rutin in oral dosage forms based on isocratic reversed phase high performance liquid chromatography (RP-HPLC) was developed and validated. Using a C(18) reverse-phase analytical column, the following conditions were chosen as optimal: mobile phase methanol-water 1:1 (v/v), pH 2.8 (adjusted with phosphoric acid), flow rate=1 mL min(-1) and temperature T=40.0 degrees C. Linearity was observed in the concentration range 8-120 microg mL(-1) with a correlation coefficient of 0.99982 and the limit of detection (LOD)=2.6 microg mL(-1), and limit of quantification (LOQ)=8.0 microg mL(-1). Intra- and inter-day precision were within acceptable limits. Robustness test indicated that the mobile phase composition and pH influence mainly the separation. The proposed method allowed direct determination of rutin in pharmaceutical dosage forms in the presence of excipients, but is not suitable for preparations where compounds structurally/chemically related to rutin may be present.

  3. Isocratic rapid liquid chromatographic method for simultaneous determination of carotenoids, retinol, and tocopherols in human serum.

    PubMed

    Thibeault, Denis; Su, Haixiang; MacNamara, Elizabeth; Schipper, Hyman M

    2009-04-15

    An improved isocratic and rapid HPLC method was developed for the measurement of carotenoids, retinol and tocopherols in human serum. Vitamins were extracted with hexane. Mobile phase consisted of a mixture acetonitrile:methylene chloride:methanol with 20 mM ammonium acetate. This method used a small bead size (3 microm) Spherisorb ODS2 column with titane frits. Diode array and fluorescence detectors were used respectively for the detection of carotenoids and retinol/tocopherols. Chromatographic separation was complete in 13 min for beta-cryptoxanthin, cis-trans-lycopene, alpha-carotene, beta-carotene, cis-beta-carotene, retinol, delta-tocopherol, gamma-tocopherol and alpha-tocopherol. Echinenone and tocol were employed as internal standards for diode array and fluorescence detection. Accuracy was validated using standard reference material (SRM) 968C. Intra-assay and inter-assay precision were respectively 0.2-7.3% and 3.6-12.6%. Sensitivity was verified using the ICH recommendations and the limit of detection (LOD) obtained was sufficient for routine clinical application.

  4. Simulation of elution profiles in liquid chromatography - II: Investigation of injection volume overload under gradient elution conditions applied to second dimension separations in two-dimensional liquid chromatography.

    PubMed

    Stoll, Dwight R; Sajulga, Ray W; Voigt, Bryan N; Larson, Eli J; Jeong, Lena N; Rutan, Sarah C

    2017-07-12

    An important research direction in the continued development of two-dimensional liquid chromatography (2D-LC) is to improve the detection sensitivity of the method. This is especially important in applications where injection of large volumes of effluent from the first dimension ((1)D) column into the second dimension ((2)D) column leads to severe (2)D peak broadening and peak shape distortion. For example, this is common when coupling two reversed-phase columns and the organic solvent content of the (1)D mobile phase overwhelms the (2)D column with each injection of (1)D effluent, leading to low resolution in the second dimension. In a previous study we validated a simulation approach based on the Craig distribution model and adapted from the work of Czok and Guiochon [1] that enabled accurate simulation of simple isocratic and gradient separations with very small injection volumes, and isocratic separations with mismatched injection and mobile phase solvents [2]. In the present study we have extended this simulation approach to simulate separations relevant to 2D-LC. Specifically, we have focused on simulating (2)D separations where gradient elution conditions are used, there is mismatch between the sample solvent and the starting point in the gradient elution program, injection volumes approach or even exceed the dead volume of the (2)D column, and the extent of sample loop filling is varied. To validate this simulation we have compared results from simulations and experiments for 101 different conditions, including variation in injection volume (0.4-80μL), loop filling level (25-100%), and degree of mismatch between sample organic solvent and the starting point in the gradient elution program (-20 to +20% ACN). We find that that the simulation is accurate enough (median errors in retention time and peak width of -1.0 and -4.9%, without corrections for extra-column dispersion) to be useful in guiding optimization of 2D-LC separations. However, this requires

  5. 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.

  6. Everolimus-eluting stents in interventional cardiology

    PubMed Central

    Townsend, Jacob C; Rideout, Phillip; Steinberg, Daniel H

    2012-01-01

    Bare metal stents have a proven safety record, but limited long-term efficacy due to in-stent restenosis. First-generation drug-eluting stents successfully countered the restenosis rate, but were hampered by concerns about their long-term safety. Second generation drug-eluting stents have combined the low restenosis rate of the first generation with improved long-term safety. We review the evolution of drug-eluting stents with a focus on the safety, efficacy, and unique characteristics of everolimus-eluting stents. PMID:22910420

  7. Determination of egg yolk xanthophylls by isocratic high-performance liquid chromatography.

    PubMed

    Brulc, Lučka; Simonovska, Breda; Vovk, Irena; Glavnik, Vesna

    2013-11-29

    An isocratic HPLC method was developed for the determination of eight xanthophylls (lutein, capsanthin, zeaxanthin, canthaxanthin, β-apo-8'-carotenal, ethyl-8'-apo-β-carotene-8'-oate, citranaxanthin and β-cryptoxanthin; registered as additives in poultry feeding) in egg yolks. Optimum separation of all-E-isomers of these xanthophylls was achieved in less than 18min on a ProntoSIL C30 column at 27°C using acetone-methanol-0.5M triethylammonium acetate buffer pH 7 14:5:1 (v/v) as the mobile phase with a flow rate of 1mL/min using spectrophotometric detection at 450nm. Other mobile phases were also found suitable, including acetone-water 93:7 (v/v) and acetone-methanol 1:4 (v/v) and the influences of column temperature on the separation and addition of triethylammonium acetate buffer pH 7 to the mobile phase on enhancement of the peak areas were evaluated. Preparation of test solution from yolks included a short vortexing of 0.5g of yolk in 10mL of acetone, followed by 15min magnetic stirring under nitrogen and centrifugation. The method was validated for 5 analytes. The calibration range was between 0.04 and 2μg/mL and the mean recovery of the analytes (95%) and the intra-day precision of the method (RSD less than 5%) on three levels in triplicates were obtained. Analyses of eggs from four husbandry classes showed the presence of up to four xanthophylls (lutein, zeaxanthin, canthaxanthin and ethyl-8'-apo-β-carotene-8'-oate) and traces of β-cryptoxanthin. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. 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

  9. Economic evaluation of sirolimus-eluting stents

    PubMed Central

    Shrive, Fiona M.; Manns, Braden J.; Galbraith, P. Diane; Knudtson, Merril L.; Ghali, William A.

    2005-01-01

    Background Sirolimus-eluting stents have recently been shown to reduce the risk of restenosis among patients who undergo percutaneous coronary intervention (PCI). Given that sirolimus-eluting stents cost about 4 times as much as conventional stents, and considering the volume of PCI procedures, the decision to use sirolimus-eluting stents has large economic implications. Methods We performed an economic evaluation comparing treatment with sirolimus-eluting and conventional stents in patients undergoing PCI and in subgroups based on age and diabetes mellitus status. The probabilities of transition between clinical states and estimates of resource use and health-related quality of life were derived from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. Information on effectiveness was based on a meta-analysis of randomized controlled clinical trials (RCTs) comparing sirolimus-eluting and conventional stents. Results Cost per quality-adjusted life year (QALY) gained in the baseline analysis was Can$58 721. Sirolimus-eluting stents were more cost-effective in patients with diabetes and in those over 75 years of age, the costs per QALY gained being $44 135 and $40 129, respectively. The results were sensitive to plausible variations in the cost of stents, the estimate of the effectiveness of sirolimus-eluting stents and the assumption that sirolimus-eluting stents would prevent the need for cardiac catheterizations in the subsequent year when no revascularization procedure was performed to treat restenosis. Interpretation The use of sirolimus-eluting stents is associated with a cost per QALY that is similar to or higher than that of other accepted medical forms of therapy and is associated with a significant incremental cost. Sirolimus-eluting stents are more economically attractive for patients who are at higher risk of restenosis or at a high risk of death if a second revascularization procedure were to be required

  10. Drug-Eluting Intraocular Lenses

    PubMed Central

    González-Chomón, Clara; Concheiro, Angel; Alvarez-Lorenzo, Carmen

    2011-01-01

    Notable advances in materials science and in surgical techniques make the management of cataract by replacement of the opaque crystalline with an intraocular lens (IOL), one of the most cost-effective interventions in current healthcare. The usefulness and safety of IOLs can be enhanced if they are endowed with the ability to load and to sustain drug release in the implantation site. Drug-eluting IOLs can prevent infections and untoward reactions of eye tissues (which lead to opacification) and also can act as drug depots for treatment of several other ocular pathologies. Such a myriad of therapeutic possibilities has prompted the design of drug-IOL combination products. Several approaches are under study, namely combination of the IOL with an insert in a single device, soaking in drug solutions, impregnation using supercritical fluids, coating with drug/polymer layers, and covalent grafting of the drug. The advantages/limitations of each technique are discussed in the present review on selected examples. Although more in vivo data are required, the information already available proves the interest of some approaches in ocular therapeutics. PMID:28824115

  11. Drug-Eluting Stents: Do They Increase Heart Attack Risk?

    MedlinePlus

    ... general, drug-eluting stents are preferred over bare-metal stents for most people. Drug-eluting stents are ... keep the blockage from recurring compared to bare metal stents. Plus, studies show the latest drug-eluting ...

  12. A simple isocratic HPLC method for the simultaneous determination of sinensetin, eupatorin, and 3'-hydroxy-5,6,7,4'-tetramethoxyflavone in Orthosiphon stamineus extracts.

    PubMed

    Yam, Mun Fei; Mohamed, Elsnoussi Ali Hussin; Ang, Lee Fung; Pei, Li; Darwis, Yusrida; Mahmud, Roziahanim; Asmawi, Mohd Zaini; Basir, Rusliza; Ahmad, Mariam

    2012-08-01

    Orthosiphon stamineus extracts contain three flavonoids (3'-hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin) as bioactive substances. Previous reported high performance liquid chromatography- ultraviolet (HPLC-UV) methods for the determination of these flavonoids have several disadvantages, including unsatisfactory separation times and not being well validated according to International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) standard guidelines. A rapid, specific reversed-phase HPLC method with isocratic elution of acetonitrile: isopropyl alcohol: 20mM phosphate buffer (NaH(2)PO(4)) (30:15:55, v/v) (pH 3.5) at a flow-rate of 1ml/minute, a column temperature of 25°C, and ultraviolet (UV) detection at 340 nm was developed. The method was validated and applied for quantification of different types of O stamineus extracts and fractions. The method allowed simultaneous determination of 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin in the concentration range of 0.03052-250 μg/ml. The limits of detection and quantification, respectively, were 0.0076 and 0.061 μg/ml for 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, 0.0153 and 0.122 μg/ml for sinensetin and 0.0305 and 0.122 μg/ml for eupatorin. The percent relative standard deviation (% RSD) values for intraday were 0.048-0.368, 0.025-0.135, and 0.05-0.476 for 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, respectively, and those for intraday precision were 0.333-1.688, 0.722-1.055, and 0.548-1.819, respectively. The accuracy for intraday were 91.25%-103.38%, 94.32%-109.56%, and 92.85%-109.70% for 3'-hydroxy-5,6,7,4'-tetramethoxyflavone, sinensetin, and eupatorin, respectively, and those for interday accuracy were 97.49%-103.92%, 103.58%-104.57%, and 103.9%-105.33%, respectively. The method was found to be simple, accurate and precise and is recommended for routine quality control analysis of O

  13. Modeling of overloaded gradient elution of nociceptin/orphanin FQ in reversed-phase liquid chromatography.

    PubMed

    Marchetti, Nicola; Dondi, Francesco; Felinger, Attila; Guerrini, Remo; Salvadori, Severo; Cavazzini, Alberto

    2005-06-24

    The Reversed-phase (RP) gradient elution chromatography of nociceptin/orphanin FQ (N/OFQ), a neuropeptide with many biological effects, has been modeled under linear and non-linear conditions. In order to do this, the chromatographic behavior has been studied under both linear and nonliner conditions under isocratic mode at different mobile phase compositions--ranging from 16 to 19% (v/v) acetonitrile (ACN) in aqueous trifluoracetic acid (TFA) 0.1% (v/v)-on a C-8 column. Although the range of mobile phase compositions investigated was quite narrow, the retention factor of this relatively small polypeptide (N/OFQ is a heptadecapeptide) has been found to change by more than 400%. In these conditions, gradient operation resulted thus to be the optimum approach for non-linear elution. As the available amount of N/OFQ was extremely reduced (only a few milligrams), the adsorption isotherms of the peptide, at the different mobile phase compositions examined, have been measured through the so-called inverse method (IM) on a 5 cm long column. The adsorption data at different mobile phase compositions have been fitted to several models of adsorption. The dependence of the isotherm parameters on the mobile phase composition was modeled by using the linear solvent strength (LSS) model and a generalized Langmuir isotherm that includes the mobile phase composition dependence. The overloaded gradient separation of N/OFQ has been modeled by numerically solving the equilibrium-dispersive (ED) model of chromatography under a selected gradient elution mode, on the basis of the previously determined generalized Langmuir isotherm. The agreement between theoretical calculations and experimental overloaded band profiles appeared reasonably accurate.

  14. Assay of tolnaftate and related impurities by isocratic supercritical fluid chromatography.

    PubMed

    Patil, S T; Bhoir, I C; Bhagwat, A M; Sundaresan, M

    2000-05-01

    Tolnaftate, an antifungal drug (TF) and related impurities arising from synthesis, viz., N-methyl-m-toluidine (NMmT) and beta-naphthol-1-chlorothio carbamate (beta-NCTC) can be determined by supercritical fluid chromatography. Even though it was possible to elute TF completely with neat SCF CO2, the peaks of the impurities were found to merge. The chromatographic figures of merit of the three analytes such as retention time (tR), capacity factor (k), selectivity factor (alpha), no. of theoretical plates (N), were optimized. The three compounds can be resolved in 5 min on a Hypersil (250 x 4.0 mm) 5 mu, C18 column with supercritical carbon dioxide, modified with 1.96% methanol as the mobile phase at 9.81 MPa and at 40 degrees C. Detection was carried out at 220 nm. The data as evaluated by the linear regression least squares fit method gave linearity ranges from 0.2 to 10.0 microg/mL for TF and NMmT and 0.3 to 10.0 microg/mL for beta-NCTC with correlation coefficients > 0.99. The method was successfully employed to estimate levels of 0.01% for NMmT and 0.02% for beta-NCTC with respect to TF.

  15. High-performance liquid chromatographic determination of cotinine in urine in isocratic mode.

    PubMed

    Ceppa, F; El Jahiri, Y; Mayaudon, H; Dupuy, O; Burnat, P

    2000-09-15

    A simple procedure for the determination of cotinine, major metabolite of nicotine in urine, is described. The assay involved a liquid-liquid extraction with dichloromethane in alkaline environment. The extract was dried at ambient temperature under a gentle stream of nitrogen. The residue was dissolved in 300 microl of mobile phase and 30 microl aliquot was injected via an automatic sampler into the liquid chromatograph and eluted with the mobile phase (10-9%, v/v methanol and acetonitrile, respectively in potassium dihydrogenphosphate buffer adjusted to pH 3.4) at a flow rate of 1 ml/min on a C8 Symmetry cartridge column (5 microm, 150 mm x 3.9 mm, Waters) at 25 degrees C. The eluate was detected at 260 nm. Internal standard was 2-phenylimidazole. Sensitive and specific, this technique was performed to test urine of diabetic patients (smokers and non-smokers) admitted in an endocrinology service. Urinary cotinine seems to be a better marker of smoking status than thiocyanates.

  16. Simultaneous Determination of Cromolyn Sodium Combined Dosage Forms Using Isocratic HPLC Method.

    PubMed

    Fathy, M E; Abo El Abass Mohamed, S; Elmansi, H; Belal, F

    2017-01-01

    A simple and selective reversed-phase high-performance liquid chromatography method was developed for the estimation of cromolyn sodium (CRM) with either oxymetazoline hydrochloride (OMZ) or xylometazoline hydrochloride (XMZ) in their binary mixtures. The method is based on the simultaneous separation of each drug in a reversed-phase Waters symmetry(®) C18 column (250 mm × 4.6 mm intradermally, 5-µm particle size) at 25°C. Elution was performed with a mobile phase consisting of methanol : 0.1 M phosphate buffer (60:40, v/v, pH 4.0). Quantitation was achieved with ultraviolet detection at 220 nm. The method could determine the three drugs, with linearity, in the range of 2.0-100.0 µg/mL for CRM and 0.8-8.0 µg/mL for OMZ and for XMZ. Aspirin was used as internal standard. Optimization of the separation in terms of mobile phase composition is critical to the method development, which is discussed in detail. The suggested procedure was successfully applied to the analysis of the studied drugs in their nasal preparations. Statistical evaluation of the data obtained by the proposed and comparison methods revealed good accuracy of the proposed method.

  17. Gradient elution isotachophoresis for enrichment and separation of biomolecules.

    PubMed

    Shackman, Jonathan G; Ross, David

    2007-09-01

    A novel format for performing capillary isotachophoresis (ITP) is described -- gradient elution ITP (GEITP). GEITP merges the recently described electrophoretic separation technique of gradient elution moving boundary electrophoresis (GEMBE) with an ITP enrichment step. GEMBE utilizes a combination of continuous sample injection with a pressure-controlled counterflow; as the counterflow is reduced, analytes are sequentially eluted onto the separation column and detected as boundary interfaces. By incorporating leading electrolytes into the counterflow and terminating electrolytes into the sample matrix, an ionic interface can be formed near the capillary inlet. The discontinuous buffer system forms highly enriched analyte zones outside of the capillary, which are then eluted onto the separation capillary as the counterflow is reduced. Separation of fluorescent analytes was achieved either through discrete electrolyte spacers added to the sample or by using ampholyte mixtures to form a continuum of spacers. As the ITP process occurs off-column, extremely short length separations can be achieved, as demonstrated by a separation in 30 microm. The effects of various parameters on the GEITP enrichment process are investigated, including initial counterflow rates, electric field, leading electrolyte concentration, and counterflow acceleration, which is an adjustable parameter allowing for highly flexible separations. Typical enhancements in limits of detection and sensitivity were greater than 10,000-fold and were achieved in less than 2 min, yielding low-picomolar detection limits using arc lamp illumination and low-cost CCD detection. An optimized system afforded greater than 100,000-fold improvement in detection of carboxyfluorescein in 8 min. Specific examples of enrichment and separation demonstrated include the following: small dye molecules, DNA, amino acid mixtures, and protein mixtures.

  18. Chiral separation of lipoxygenase metabolites utilizing high-performance liquid chromatography.

    PubMed

    Myrdal, Paul B; Angersbach, B Steven; Karlage, Kelly; Kuehl, Philip J

    2006-11-03

    An isocratic, reversed-phase HPLC assay has been developed for the separation of the enantiomers of four lipoxygenase metabolites, without the need for a derivatization step. Separation of the enantiomers was studied on a polysaccharide type chiral stationary phase column. Upon determination of suitable mobile phase composition, the assay was evaluated at various temperatures. In all cases the R enantiomer eluted before the S enantiomer. The best separations were observed at 0 degrees C.

  19. 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.

  20. 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.

  1. 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.

  2. Use of a novel elution regimen reveals the dominance of polyreactive antinuclear autoantibodies in lupus kidneys.

    PubMed

    Xie, Chun; Liang, Zhiyan; Chang, Sooghee; Mohan, Chandra

    2003-08-01

    The autoantibody specificities that dominate the deposits in lupus kidneys remain unclear. Reasoning that previously utilized elution buffers such as acidic glycine and ammonium thiocyanate may not have been maximally effective in eluting all Ig deposits from the kidneys, this study was conducted to experiment with a stronger dissociating agent, urea-glycine. Seven antinuclear antibody-positive, nephritic female (SWR x NZB)F(1) (SNF1) lupus mice were selected for the elution study. Deposited Ig was eluted from their kidneys using 3 different elution buffers: 0.15M glycine-HCl buffer, 1.3M ammonia thiocyanate/0.15M glycine-HCl buffer, and 5M urea/0.15M glycine-HCl buffer. All eluates were tested for specificity against a variety of nuclear and glomerular antigens. Compared with conventional elution buffers, the urea-based regimen eluted severalfold more IgG and IgM antinuclear antibodies from the kidneys of nephritic SNF1 lupus mice. IgG anti-double-stranded DNA (anti-dsDNA) antibodies were not only the most prevalent species in these renal deposits, they were also heavily enriched in the kidneys, relative to the corresponding serum levels. A substantial fraction of the anti-single-stranded DNA and antihistone/DNA (but not antihistone) reactivity in these eluates was due to cross-reactive anti-dsDNA antibodies. No reactivity with SSA, SSB, Sm, RNP, Jo-1, Scl-70, or ribosomal P antigens could be demonstrated in these eluates. Importantly, the urea-glycine eluates differed from the conventional eluates in having significantly greater reactivity to glomerular substrate and laminin. This novel urea-based elution provides further support for the dominance of antibodies in lupus kidneys, with strong polyreactivity to DNA and glomerular substrate.

  3. An Isocratic High-Performance Liquid Chromatography Assay for CYP7A1-Catalyzed Cholesterol 7α-Hydroxylation.

    PubMed

    Waxman, David J; Chang, Thomas K H

    2006-01-01

    A normal-phase, isocratic high-performance liquid chromatography assay is described for cholesterol 7α-hydroxylation catalyzed by CYP7A1, which corresponds to the first and rate-limiting step in the conversion of cholesterol into bile acids. This method is based on the conversion of the primary cytochrome P450 metabolite, 7α-hydroxycholesterol, into 7α-hydroxy-4-cholesten-3-one in a reaction catalyzed by exogenous cholesterol oxidase, followed by chromatographic separation with monitoring at 254 nm. This technique is applicable to enzymatic studies for determination of cholesterol 7α- hydroxylation activity catalyzed by cDNA-expressed CYP7A1 and animal or human liver microsomes.

  4. Two-column sequential injection chromatography for fast isocratic separation of two analytes of greatly differing chemical properties.

    PubMed

    Šatínský, Dalibor; Chocholouš, Petr; Válová, Olga; Hanusová, Lucia; Solich, Petr

    2013-09-30

    This paper deals with a novel approach to separate two analytes with different chemical properties and different lipophilicity. The newly described methodology is based on the two column system that was used for isocratic separation of two analytes with very different lipophilicity-dexamethasone and cinchocaine. Simultaneous separation of model compounds cinchocaine and dexamethasone was carried under the following conditions in two-column sequential injection chromatography system (2-C SIC). A 25×4.6 mm C-18 monolithic column was used in the first dimension for retention and separation of dexamethasone with mobile phase acetonitrile:water 30:70 (v/v), flow rate 0.9 mL min(-1) and consumption of 1.7 mL. A 10×4.6 mm C-18 monolithic column with 5×4.6 mm C-18 precolumn was used in the second dimension for retention and separation of cinchocaine using mobile phase acetonitrile:water 60:40 (v/v), flow rate 0.9 mL min(-1) and consumption 1.5 mL. Whole analysis time including both mobile phase's aspirations and both column separations was performed in less than 4 min. The method was fully validated and used for determination of cinchocaine and dexamethasone in pharmaceutical otic drops. The developed 2-C SIC method was compared with HPLC method under the isocratic conditions of separation on monolithic column (25×4.6 mm C-18). Spectrophotometric detection of both compounds was performed at wavelength 240 nm. System repeatability and method precision were found in the range (0.39-3.12%) for both compounds. Linearity of determination was evaluated in the range 50-500 μg mL(-1) and coefficients of determination were found to be r(2)=0.99912 for dexamethasone and r(2)=0.99969 for cinchocaine. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Paclitaxel-Eluting versus Everolimus-Eluting Coronary Stents in Diabetes.

    PubMed

    Kaul, Upendra; Bangalore, Sripal; Seth, Ashok; Arambam, Priyadarshini; Abhaichand, Rajpal K; Abhaychand, Rajpal K; Patel, Tejas M; Banker, Darshan; Abhyankar, Atul; Mullasari, Ajit S; Shah, Sanjay; Jain, Rajneesh; Kumar, Premchand R; Bahuleyan, C G

    2015-10-29

    The choice of drug-eluting stent in the treatment of patients with diabetes mellitus and coronary artery disease who are undergoing percutaneous coronary intervention (PCI) has been debated. Previous studies comparing paclitaxel-eluting stents with stents eluting rapamycin (now called sirolimus) or its analogues (everolimus or zotarolimus) have produced contradictory results, ranging from equivalence between stent types to superiority of everolimus-eluting stents. We randomly assigned 1830 patients with diabetes mellitus and coronary artery disease who were undergoing PCI to receive either a paclitaxel-eluting stent or an everolimus-eluting stent. We used a noninferiority trial design with a noninferiority margin of 4 percentage points for the upper boundary of the 95% confidence interval of the risk difference. The primary end point was target-vessel failure, which was defined as a composite of cardiac death, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization at the 1-year follow-up. At 1 year, paclitaxel-eluting stents did not meet the criterion for noninferiority to everolimus-eluting stents with respect to the primary end point (rate of target-vessel failure, 5.6% vs. 2.9%; risk difference, 2.7 percentage points [95% confidence interval, 0.8 to 4.5]; relative risk, 1.89 [95% confidence interval, 1.20 to 2.99]; P=0.38 for noninferiority). There was a significantly higher 1-year rate in the paclitaxel-eluting stent group than in the everolimus-eluting stent group of target-vessel failure (P=0.005), spontaneous myocardial infarction (3.2% vs. 1.2%, P=0.004), stent thrombosis (2.1% vs. 0.4%, P=0.002), target-vessel revascularization (3.4% vs. 1.2%, P=0.002), and target-lesion revascularization (3.4% vs. 1.2%, P=0.002). In patients with diabetes mellitus and coronary artery disease undergoing PCI, paclitaxel-eluting stents were not shown to be noninferior to everolimus-eluting stents, and they resulted in higher rates of target

  6. 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

  7. An isocratic HPLC method for the determination of sorbitol and glycerol in pharmaceutical formulations.

    PubMed

    Simonzadeh, Ninus; Ronsen, Bruce

    2012-08-01

    Sorbitol and glycerol, along with other inactive ingredients such as preservatives and dyes, are commonly used in various pharmaceutical and personal care products. To accurately assess the effectiveness of various formulations containing sorbitol and/or glycerol, their quantitative determination is essential. In the current study, two types of detectors (a Varian evaporative light scattering detector and an Agilent ultraviolet-visible detector) are evaluated for the assay of working sample solutions. The two detection techniques are complimentary, and a comparison of the results obtained using the two detectors is presented here. The current method is shown to be stability-indicating and free from interference from any of the formulation excipients and potential degradation products. The method is reproducible, accurate, sensitive and selective. It provides enhanced detection sensitivity for sorbitol and comparable sensitivity for glycerol versus similar methods reported in the literature that utilize a refractive index detector for the analysis of either of the two polyols.

  8. 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.

  9. 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.

  10. Changes in the mobile phase composition on a stepwise counter-current chromatography elution for the isolation of flavonoids from Siparuna glycycarpa.

    PubMed

    Costa, Fernanda das Neves; Garrard, Ian; da Silva, Antonio Jorge Ribeiro; Leitão, Gilda Guimarães

    2013-07-01

    This paper describes the isolation of flavonoids and other aromatic compounds from an ethyl acetate extract of leaves of Siparuna glycycarpa using stepwise elution counter-current chromatography (CCC). The elution profile yielded the following compounds: diglycosylated flavonoids, quercetin 3-O-rutinoside and quercetin 7-O-rutinoside, followed by monoglycosylated flavonoids, kaempferol-3-O-β-glucopyranoside, kaempferol-3-O-β-rhamnopiranoside, kaempferol-3-O-β-6''(p-coumaroyl) glucopyranoside, and quercetin-3-O-β-glucopyranoside, and then free phenolics, protocatechuic acid, and 2',6'-dihydroxy-4, 4'-dimethoxydihydrochalcone, which shows that this type of elution covers a broader range of polarity than the traditional isocratic mode. This makes it more suitable to perform separations of mixtures containing large differences in hydrophobicity. A GC analysis of a blank CCC run was performed to determine if changes in the mobile phase composition affect the chromatographic process. Results showed a gradual variation of the composition of the mobile phase emerging after the step gradient, favoring the selectivity of the solvent system.

  11. 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

  12. Sirolimus-eluting coronary stents: a review

    PubMed Central

    Abizaid, Alexandre

    2007-01-01

    The sirolimus-eluting coronary stent received CE Mark approval in Europe in April 2002. In the US, FDA approval followed in April 2003. Since the preliminary results from the First-in-Man feasibility study were presented, several randomized, controlled trials have documented the profound antiproliferative effects of sirolimus, a macrolide antibiotic and potent cytostatic inhibitor of smooth muscle cell proliferation. Subsequently, the body of clinical evidence was increased by the second wave of evidence from trials in more complex lesions (such as in-stent restenosis, small vessels, chronic total occlusions) and “high-risk” patients such as those with diabetes. More recently we have had the opportunity to compare the two commercially available drug-eluting stents following the presentation of data from six head-to-head trials. As a result of numerous single and multi-center, national and international studies in which the safety and efficacy of sirolimus-eluting coronary stents have been subjected to close scrutiny, the global interventional cardiology community now has a wealth of evidence in support of the use of this technology resulting in dramatically improved patient outcomes after percutaneous intervention. PMID:17580729

  13. Isocratic separation of ginsenosides by high-performance liquid chromatography on a diol column at subambient temperatures.

    PubMed

    Lou, Da-Wei; Saito, Yoshihiro; Zarzycki, Paweł K; Ogawa, Mitsuhiro; Jinno, Kiyokatsu

    2006-05-01

    An improved high-performance liquid chromatographic method for separation of a number of ginsenosides has been developed. The influence of temperature (from 0 to 25 degrees C) on the retention and separation of the ginsenosides was studied by applying a binary mobile phase (acetonitrile/water, 82:18 v/v) and a diol column (LiChrospher 100 Diol). The column temperature is one of the more important parameters for the retention and separation of the components investigated. Selected thermodynamic parameters, including changes of enthalpy (deltaH degrees) and entropy (deltaS degrees), were estimated from linear van't Hoff plots, and possible retention mechanisms were discussed. Moreover, the best separation conditions were selected based on optimization criteria including maximum retention time (t(R max)), minimum resolution (R(s min)), and relative resolution product (r). Temperature regions close to 14 degrees C offered the highest selectivity and almost equal distribution of the ginsenosides peaks across the chromatogram. Under such isocratic conditions, excellent separation of chromatographic standards and selected ginseng samples was achieved in less than 16 min.

  14. Retinol, alpha-tocopherol, lycopene, and alpha- and beta-carotene simultaneously determined in plasma by isocratic liquid chromatography.

    PubMed

    Milne, D B; Botnen, J

    1986-05-01

    Retinol, alpha-tocopherol, lycopene, and alpha- and beta-carotene can be simultaneously determined in human plasma by reversed-phase liquid chromatography. Plasma--0.5 mL plus added internal standard, retinyl acetate--is deproteinized with 0.5 mL of ethanol, then extracted with 1.0 mL of petroleum ether. The organic layer is removed and evaporated, the residue is redissolved in 0.25 mL of ethanol, and 8-microL samples are injected into a 60 X 4.6 mm column of Hypersil ODS 3-microns particles at 35 degrees C. An isocratic methanol mobile phase, flow rate 0.9 mL/min, is used for the 9-min run. Retinol and retinyl acetate are monitored at 305 nm, the tocopherols at 292 nm, and the carotenoids at 460 nm. Between-run CVs were 3.1, 6.9, 6.1, and 6.5% for retinol, alpha-tocopherol, lycopene, and beta-carotene, respectively. Small sample requirement, simplicity of extraction, short run time, and good reproducibility make this procedure ideal for clinical or research use.

  15. Diffuse Interface Methods for Modeling Drug-Eluting Stent Coatings.

    PubMed

    Saylor, David M; Forrey, Christopher; Kim, Chang-Soo; Warren, James A

    2016-02-01

    An overview of diffuse interface models specific to drug-eluting stent coatings is presented. Microscale heterogeneities, both in the coating and use environment, dictate the performance of these coatings. Using diffuse interface methods, these heterogeneities can be explicitly incorporated into the model equations with relative ease. This enables one to predict the complex microstructures that evolve during coating fabrication and subsequent impact on drug release. Examples are provided that illustrate the wide range of phenomena that can be addressed with diffuse interface models including: crystallization, constrained phase separation, hydrolytic degradation, and heterogeneous binding. Challenges associated with the lack of material property data and numerical solution of the model equations are also highlighted. Finally, in light of these potential drawbacks, the potential to utilize diffuse interface models to help guide product and process development is discussed.

  16. 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

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

    PubMed

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

    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.

  18. 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.

  19. Determination of hydroxycinnamic acids and volatile phenols in wort and beer by isocratic high-performance liquid chromatography using electrochemical detection.

    PubMed

    Vanbeneden, Nele; Delvaux, Filip; Delvaux, Freddy R

    2006-12-15

    The suitability of a simple and rapid isocratic RP-HPLC method with amperometric electrochemical detection for the simultaneous detection and quantification of hydroxycinnamic acids and their corresponding aroma-active volatile phenols in wort and beer is reported. The technique gives good specificity and sensitivity, and can therefore be used for routine monitoring of hydroxycinnamic acids in wort and the development of volatile phenolic flavour compounds during the beer production process and subsequent conservation.

  20. A novel isocratic HPLC method to separate and quantify acetanilide and its hydroxy aromatic derivatives: 2-, 3- and 4-hydroxyacetanilide (paracetamol or acetaminophen).

    PubMed

    Mancilla, J; Valdes, E; Gil, L

    1989-01-01

    Reverse-phase high performance liquid chromatography on a microBondapak C-18 Column has been used to separate and quantify acetanilide and its aromatic monohydroxy derivatives in the 2-, 3- and 4- positions. Separation was achieved within 22 min by using an isocratic mixture of 2-propanol: methanol: water, 8:18:74 (v/v). This method compares very favourably with other HPLC techniques already reported to separate acetanilide from the monohydroxy aromatic derivatives.

  1. Simultaneous determination of mycophenolic acid and its glucuronides in human plasma using isocratic ion pair high-performance liquid chromatography.

    PubMed

    Mino, Yasuaki; Naito, Takafumi; Matsushita, Tomomi; Kagawa, Yoshiyuki; Kawakami, Junichi

    2008-02-13

    Therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) following administration of mycophenolate mofetil (MMF) or the enteric-coated sodium salt of MPA formulations, seems beneficial because of the large intra- and inter-individual variability in MPA pharmacokinetics. MPA is an active component from these oral formulations and are further metabolised to inactive phenolic glucuronide (MPAG) and active acyl glucuronide (AcMPAG). This study aims to determine simultaneously these three metabolites of MMF using isocratic ion pair HPLC and to evaluate the short-term stability of AcMPAG in human plasma. Samples were prepared using solid phase extraction. Chromatographic separation was achieved over an RP column (TSKgel ODS-80Ts, 150 mm x 4.6 mm i.d., 5 microm particle size) with acetonitrile and 30 mM tetra-n-butylammonium bromide containing 5 mM ammonium acetate at pH 9.0 (33/67, v/v) as the mobile phase. The flow rate of the mobile phase was 1ml/min, and the wavelength of determination by UV detection was 250 nm (run time, 16 min). Calibration curves for MPA, MPAG and AcMPAG in human plasma were linear over a concentration range of 0.05-50, 0.1-400 and 0.08-8 microg/ml, respectively. Intra- and inter-assay R.S.D. were<6.5%. Extraction efficiencies were more than 85% for all analytes. Since AcMPAG was unstable in human plasma, plasma acidification was needed for the quantification of AcMPAG. Large interindividual variability was observed in the AcMPAG pharmacokinetics in the early period after renal transplantation. In conclusion, a simple, accurate and reproducible HPLC method to measure simultaneously these three MMF metabolites has been established. The method will be helpful in evaluating pharmacokinetics of MPA and its glucuronides.

  2. A Drug-Eluting Contact Lens

    PubMed Central

    Ciolino, Joseph B.; Hoare, Todd R.; Iwata, Naomi G.; Behlau, Irmgard; Dohlman, Claes H.; Langer, Robert; Kohane, Daniel S.

    2014-01-01

    Purpose To formulate and characterize a drug-eluting contact lens designed to provide extended, controlled release of a drug. Methods Prototype contact lenses were created by coating PLGA (poly[lactic-co-glycolic acid]) films containing test compounds with pHEMA (poly[hydroxyethyl methacrylate]) by ultraviolet light polymerization. The films, containing encapsulated fluorescein or ciprofloxacin, were characterized by scanning electron microscopy. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. Ciprofloxacin eluted from the contact lens was studied in an antimicrobial assay to verify antimicrobial effectiveness. Results After a brief and minimal initial burst, the prototype contact lenses demonstrated controlled release of the molecules studied, with zero-order release kinetics under infinite sink conditions for over 4 weeks. The rate of drug release was controlled by changing either the ratio of drug to PLGA or the molecular mass of the PLGA used. Both the PLGA and the pHEMA affected release kinetics. Ciprofloxacin released from the contact lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested. Conclusions A prototype contact lens for sustained drug release consisting of a thin drug-PLGA film coated with pHEMA could be used as a platform for ocular drug delivery with widespread therapeutic applications. PMID:19136709

  3. Vascular pathology of drug-eluting stents.

    PubMed

    Nakazawa, Gaku; Finn, Aloke V; Virmani, Renu

    2007-06-01

    Polymer-based sirolimus- (Cypher) and paclitaxel-eluting stents (Taxus), so-called drug-eluting stents (DES), have become the treatment of choice for patients with symptomatic coronary artery disease undergoing percutaneous coronary revascularization (PCI). While these stents have reduced rates of restenosis and late lumen loss compared to bare-metal stents (BMS), late thrombosis, a life-threatening complication of this technology, has emerged as a major concern. Our understanding of the pathophysiology of late DES thrombosis is derived from animal and human pathologic samples taken after implantation of these devices. These data indicate that the DES cause substantial impairment in arterial healing characterized by lack of complete reendothelialization and persistence of fibrin when compared to BMS. This so-called delayed healing is "identified as" the primary substrate of an underlying cause of late DES thrombosis at autopsy. Several additional risk factors for late stent thrombosis include penetration of necrotic core, malapposition, overlapping stent placement, excessive stent length, and bifurcation lesions. These represent additional barriers to healing and should be avoided if DES are to be used in order to minimize the late thrombotic risks of these devices. Since the time course of complete healing with DES is unknown, the optimal duration of antiplatelet treatment remains to be determined.

  4. 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.

  5. Drug-eluting balloons in below the knee treatment.

    PubMed

    VAN DEN Berg, Jos C

    2016-12-01

    The endovascular treatment of atherosclerotic disease of the infra-inguinal arteries has changed significantly since the introduction of drug-eluting balloon technology. The role of angioplasty using drug-eluting balloons for lesions of the superficial femoral and popliteal artery is now well established. The positive results of the use of drug-eluting balloons in the above knee segment could not be achieved in the below-the-knee segment. This paper will give an overview of the current status of drug-eluting balloon angioplasty for below-the-knee lesions, and will present a review of 2 single center registry, 5 randomized trials and a meta-analysis.

  6. Evaluation of Elution Parameters for Cesium Ion Exchange Resins

    SciTech Connect

    Burgeson, Ingrid E.; Deschane, Jaquetta R.; Cook, Bryan J.; Blanchard, David L.; Weier, Dennis R.

    2006-08-28

    Cesium ion exchange is one of the planned processes for treating and disposing of waste at the U.S. Department of Energy Hanford Site. Radioactive supernatant liquids from the waste tanks will undergo ultrafiltration, followed by cesium ion exchange using a regenerable organic ion exchange resin. Two resins, SuperLig?644 and a Resorcinol-formaldehyde resin are being evaluated for cesium removal and cesium elution characteristics. The main purpose of this study is to optimize the cesium elution to provide a resin which after undergoing elution would meet the U.S. Department of Energy/Office of River Protection Project-Waste Treatment Plant processing and resin disposal criteria. Columns of each resin type were loaded to greater or equal to 90% breakthrough with a Hanford waste stimulant and eluted with nitric acid. The temperature, flow rate and nitric acid concentration were varied to determine the optimal elution conditions. Temperature and eluant flow rate were the most important elution parameters. As would be predicted based upon kinetic consideration alone, decreasing the eluant flow rate and increasing the temperature provided the optimal elution conditions. Varying the nitric acid concentration did not have a significant effect on the elution; however, elutions performed using both high acid concentration (1M) and elevated temperature (45 C) resulted in resin degradation, causing gas generation and resin bed disruption.

  7. 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.

  8. Gradient elution in aqueous normal-phase liquid chromatography on hydrosilated silica-based stationary phases.

    PubMed

    Soukup, Jan; Janás, Petr; Jandera, Pavel

    2013-04-19

    The possibility of applying a theoretical model in the prediction of the retention of phenolic acids on hydrosilated silica, in aqueous normal phase mode was studied. The actual gradient of the aqueous component in acetonitrile may fluctuate from the pre-set program, as even the gradient-grade acetonitrile contains some water. Hence, the actual concentration of water during the gradient run is higher than pre-set by the gradient program, which leads to lower than expected sample retention. Furthermore, the actual gradient profile may be affected by an increase in water uptake on a polar column during the gradient run. These effects were investigated using the using frontal analysis method and Karl-Fischer titration, for the determination of water in the initial mobile phase, and in the column effluent. Preferential adsorption of water on the Silica hydride, Diamond hydride, UDC Cholesterol, Bidentate C18, and Phenyl hydride columns can be described by Langmuir isotherms. At the column saturation capacity, less than one monomolecular water layer is adsorbed, with a further decrease in coverage density for modified materials. Parameters of semi-logarithmic and logarithmic model equations, describing the dependence of retention factor on the concentration of water, were determined under isocratic conditions. These parameters and linear gradient profiles corrected for the actual water concentrations were used in calculation of gradient retention data. The corrections for the actual water concentration greatly improved the agreement between the experiment and the predicted gradient elution volumes. Generally, the semi-logarithmic model provides slightly better prediction of the gradient data, with respect to the logarithmic retention model. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. Drug-eluting stents below the knee.

    PubMed

    Bosiers, M; Deloose, K; Callaert, J; Keirse, K; Verbist, J; Peeters, P

    2011-04-01

    The fear that early thrombosis and late luminal loss due to intimal hyperplasia formation potentially leads to insufficient long-term patency rates can explain the reluctance on implanting stents in small diameter below-the-knee (BTK) arteries. Drug-eluting stent (DES) technology was developed to prevent early thrombosis and late luminal loss to potentially improve long-term patency rates. Currently, the first level 1 evidence from prospective, randomized, controlled DESTINY and ACHILLES studies indicate that the implantation of DES in short lesion lenghts in the infrapopliteal vasculature leads to favorable outcomes with high primary patency rates. This makes that primary DES placement can be recommended as treatment strategy in short BTK-lesions.

  10. Drug eluting stents for vulnerable plague.

    PubMed

    Toutouzas, Konstantinos; Synetos, Andreas; Stefanadis, Christodoulos

    2010-01-01

    A vulnerable plaque is an atheromatic plaque with specific morphological characteristics, mainly presented as an unstable collection of white blood cells and lipids in the wall of an artery. It is of great importance to adequately recognize and treat this entity before its rupture, before the initiation of an acute coronary syndrome. The search of the location of future plaque ruptures or plaque erosions is an important area of cardiovascular research. Systemic therapy, including use of statins, targets the vulnerable patient. However, adverse events cannot be completely eliminated with the appropriate application of systemic therapies and this has given rise to efforts for evolution of local or regional therapies of the vulnerable plaques to prevent future events. Recently drug eluting stents dedicated to vulnerable plaques have been developed, aiming in the local stabilization of the vulnerable plaque.

  11. Everolimus-eluting stents: update on current clinical studies.

    PubMed

    Allocco, Dominic J; Joshi, Anita A; Dawkins, Keith D

    2011-01-01

    Everolimus-eluting stents (EES) have become the most commonly implanted coronary stents worldwide. This review describes and analyzes the clinical data supporting the use of EES, focusing primarily on published, randomized, controlled trials. Everolimus-eluting stents have been shown to have less restenosis, stent thrombosis, and periprocedural myocardial infarction compared with earlier generation paclitaxel-eluting stents (PES). Lower rates of adverse events for EES compared with PES were generally seen in all subgroups, with the notable exception of patients with diabetes mellitus. There have been fewer, randomized, clinical trials comparing EES with either sirolimus-eluting stents or zotarolimus-eluting stents, although very good results with EES have been observed in the trials that have been performed. Recent clinical trial data suggest that this excellent safety and efficacy profile is maintained in a next-generation EES designed to have improved mechanical properties and radiopacity.

  12. Functional Nanoarchitectures For Enhanced Drug Eluting Stents

    NASA Astrophysics Data System (ADS)

    Saleh, Yomna E.; Gepreel, Mohamed A.; Allam, Nageh K.

    2017-01-01

    Different strategies have been investigated to allow for optimum duration and conditions for endothelium healing through the enhancement of coronary stents. In this study, a nanoarchitectured system is proposed as a surface modification for drug eluting stents. Highly oriented nanotubes were vertically grown on the surface of a new Ni-free biocompatible Ti-based alloy, as a potential material for self-expandable stents. The fabricated nanotubes were self-grown from the potential stent substrate, which are also proposed to enhance endothelial proliferation while acting as drug reservoir to hinder Vascular Smooth Muscle Cells (VSMC) proliferation. Two morphologies were synthesized to investigate the effect of structure homogeneity on the intended application. The material was characterized by field-emission scanning electron microscope (FESEM), X-ray diffraction (XRD), Raman spectroscopy, energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). Nanoindentation technique was used to study the mechanical properties of the fabricated material. Cytotoxicity and proliferation studies were performed and compared for the two fabricated nanoarchitectures, versus smooth untextured samples, using in-vitro cultured endothelial cells. Finally, the drug loading capacity was experimentally studied and further supported by computational modeling of the release profile.

  13. Functional Nanoarchitectures For Enhanced Drug Eluting Stents

    PubMed Central

    Saleh, Yomna E.; Gepreel, Mohamed A.; Allam, Nageh K.

    2017-01-01

    Different strategies have been investigated to allow for optimum duration and conditions for endothelium healing through the enhancement of coronary stents. In this study, a nanoarchitectured system is proposed as a surface modification for drug eluting stents. Highly oriented nanotubes were vertically grown on the surface of a new Ni-free biocompatible Ti-based alloy, as a potential material for self-expandable stents. The fabricated nanotubes were self-grown from the potential stent substrate, which are also proposed to enhance endothelial proliferation while acting as drug reservoir to hinder Vascular Smooth Muscle Cells (VSMC) proliferation. Two morphologies were synthesized to investigate the effect of structure homogeneity on the intended application. The material was characterized by field-emission scanning electron microscope (FESEM), X-ray diffraction (XRD), Raman spectroscopy, energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). Nanoindentation technique was used to study the mechanical properties of the fabricated material. Cytotoxicity and proliferation studies were performed and compared for the two fabricated nanoarchitectures, versus smooth untextured samples, using in-vitro cultured endothelial cells. Finally, the drug loading capacity was experimentally studied and further supported by computational modeling of the release profile. PMID:28079127

  14. Array tomography: immunostaining and antibody elution.

    PubMed

    Micheva, Kristina D; O'Rourke, Nancy; Busse, Brad; Smith, Stephen J

    2010-11-01

    Array tomography is a volumetric microscopy method based on physical serial sectioning. Ultrathin sections of a plastic-embedded tissue are cut using an ultramicrotome, bonded in an ordered array to a glass coverslip, stained as desired, and imaged. The resulting two-dimensional image tiles can then be reconstructed computationally into three-dimensional volume images for visualization and quantitative analysis. The minimal thickness of individual sections permits high-quality rapid staining and imaging, whereas the array format allows reliable and convenient section handling, staining, and automated imaging. Also, the physical stability of the arrays permits images to be acquired and registered from repeated cycles of staining, imaging, and stain elution, as well as from imaging using multiple modalities (e.g., fluorescence and electron microscopy). Array tomography makes it possible to visualize and quantify previously inaccessible features of tissue structure and molecular architecture. However, careful preparation of the tissue is essential for successful array tomography; these steps can be time-consuming and require some practice to perfect. In this protocol, tissue arrays are prepared for imaging by tagging with primary antibodies against specific cellular targets, followed by labeling with fluorescent secondary antibodies. Alternatively, fluorescent proteins that have been introduced into the tissue before dissection can be used.

  15. Functional Nanoarchitectures For Enhanced Drug Eluting Stents.

    PubMed

    Saleh, Yomna E; Gepreel, Mohamed A; Allam, Nageh K

    2017-01-12

    Different strategies have been investigated to allow for optimum duration and conditions for endothelium healing through the enhancement of coronary stents. In this study, a nanoarchitectured system is proposed as a surface modification for drug eluting stents. Highly oriented nanotubes were vertically grown on the surface of a new Ni-free biocompatible Ti-based alloy, as a potential material for self-expandable stents. The fabricated nanotubes were self-grown from the potential stent substrate, which are also proposed to enhance endothelial proliferation while acting as drug reservoir to hinder Vascular Smooth Muscle Cells (VSMC) proliferation. Two morphologies were synthesized to investigate the effect of structure homogeneity on the intended application. The material was characterized by field-emission scanning electron microscope (FESEM), X-ray diffraction (XRD), Raman spectroscopy, energy dispersive X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). Nanoindentation technique was used to study the mechanical properties of the fabricated material. Cytotoxicity and proliferation studies were performed and compared for the two fabricated nanoarchitectures, versus smooth untextured samples, using in-vitro cultured endothelial cells. Finally, the drug loading capacity was experimentally studied and further supported by computational modeling of the release profile.

  16. 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.

  17. 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.

  18. Second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice (COMPARE): a randomised trial.

    PubMed

    Kedhi, Elvin; Joesoef, Kaiyum Sheik; McFadden, Eugene; Wassing, Jochem; van Mieghem, Carlos; Goedhart, Dick; Smits, Pieter Cornelis

    2010-01-16

    Everolimus-eluting and paclitaxel-eluting stents, compared with bare metal stents, reduced the risk of restenosis in clinical trials with strict inclusion and exclusion criteria. We compared the safety and efficacy of the second-generation everolimus-eluting and paclitaxel-eluting stents in real-life practice. We randomly assigned 1800 consecutive patients (aged 18-85 years) undergoing percutaneous coronary intervention at one centre to treatment with everolimus-eluting or paclitaxel-eluting stents. The primary endpoint was a composite of safety and efficacy (all-cause mortality, myocardial infarction, and target vessel revascularisation) within 12 months. Patients were not told which stent they had been allocated. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01016041. Follow-up was completed in 1797 patients. The primary endpoint occurred in 56 (6%) of 897 patients in the everolimus-eluting stent group versus 82 (9%) of 903 in the paclitaxel-eluting stent group (relative risk 0.69 [95% CI 0.50-0.95], p value for superiority=0.02). The difference was attributable to a lower rate of stent thrombosis (6 [<1%] vs 23 [3%], 0.26 [0.11-0-64], p=0.002), myocardial infarction (25 [3%] vs 48 [5%], 0.52 [0.33-0.84], p=0.007), and target vessel revascularisation (21 [2%] vs 54 [6%], 0.39 [0.24-0.64], p=0.0001). Cardiac death, non-fatal myocardial infarction, or target lesion revascularisation occurred in 44 [5%] patients in the everolimus-eluting stent group versus 74 [8%] patients in the paclitaxel-eluting stent group, p value for superiority was 0.005. The everolimus-eluting stent is better than the second generation paclitaxel-eluting stent in unselected patients in terms of safety and efficacy. On the basis of our results, we suggest that paclitaxel-eluting stents should no longer be used in everyday clinical practice. Unrestricted grants from Abbott Vascular and Boston Scientific. Copyright 2010 Elsevier Ltd. All rights

  19. Drug-eluting technologies in femoral artery lesions.

    PubMed

    Deloose, K; Lauwers, K; Callaert, J; Maene, L; Keirse, K; Verbist, J; Peeters, P; Bosiers, M

    2013-04-01

    The treatment of femoropopliteal lesions has known an important evolution in the last years. An important limitation of current endovascular therapy remains the occurrence of restenosis. In order to minimize restenosis rates, drug eluting technologies are evolving. The use of drug-eluting stents (DES) in coronary arteries shows beneficial results, leading to investigation of DES in femoropopliteal arteries. In this article, we give an overview of current available data on treatment with drug eluting technologies in the superficial femoral artery (SFA). This paper summarizes also the current available data of the use of drug-coated balloons (DCB) in the femoropopliteal tract. Currently, no data are available on the use of DCB in long lesions. A drug eluting bioresorbable scaffold seems to be very promising in coronary arteries. The transfer to the peripheral area is nowadays ongoing. Which technique and device for which lesion and patient requires further investigation to build up a real evidence based SFA treatment strategy.

  20. One-step purification of epigallocatechin gallate from crude green tea extracts by isocratic hydrogen bond adsorption chromatography on beta-cyclodextrin substituted agarose gel media.

    PubMed

    Xu, Jun; Zhang, Guifeng; Tan, Tianwei; Janson, Jan-Christer

    2005-09-25

    An oligomerized beta-cyclodextrin ligand coupled to brominated allyl-group substituted Sepharose HP has been used for the one-step purification of polyphenolic epigallocatechin gallate (EGCG), an important antioxidant, by isocratic hydrogen bond adsorption chromatography. With a sample load of 1.33 mg crude green tea polyphenolic extract per ml column packing and with water/ethanol/acetonitrile (57/30/13, v/v) as the optimum mobile phase, an EGCG purity of about 98% with a recovery of approximate 73% could be achieved by proper peak cutting. After about 10 sample applications, the column performance started to deteriorate but could be regenerated to its original function by cleaning with 0.35 M NaOH.

  1. 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.

  2. 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

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

    PubMed

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

    2013-07-07

    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.

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

    PubMed

    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.

  5. 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

  6. Drug-eluting stents: some first-generation problems.

    PubMed

    Murphy, Bruce E

    2004-01-01

    The recent fervor surrounding the introduction of drug-eluting stents into the practice of cardiology has proven to be problematic. The experience with the Cypher Sirolimus-Eluting Coronary Stent (Cordis Corp., Miami Lakes, FL) at Arkansas Heart Hospital progressed from anxious anticipation to complete removal of the stent from inventory in a 6-month period. Several cases involving edge dissection and subacute thrombosis were the catalyst for the decision to cease use of the device. While new products may entice, each new modality must be approached with measured enthusiasm. Drug-eluting stents are first-generation devices that may have unexposed flaws when used as first-line treatment in routine practice. The first-generation Cypher stent, as with many new devices, offers treatment-not a cure-for coronary atherosclerosis and enhances the desire for an evolved product.

  7. Linear isotherm determination from linear gradient elution experiments.

    PubMed

    Pfister, David; Steinebach, Fabian; Morbidelli, Massimo

    2015-01-02

    A procedure to estimate equilibrium adsorption parameters as a function of the modifier concentration in linear gradient elution chromatography is proposed and its reliability is investigated by comparison with experimental data. Over the past decades, analytical solutions of the so-called equilibrium model under linear gradient elution conditions were derived assuming that proteins and modifier molecules access the same fraction of the pore size distribution of the porous particles. The present approach developed in this work accounts for the size exclusion effect resulting in different exclusions for proteins and modifier. A new analytical solution was derived by applying perturbation theory for differential equations, and the 1st-order approximated solution is presented in this work. Eventually, a turnkey and reliable procedure to efficiently estimate isotherm parameters as a function of modifier concentration from linear gradient elution experiments is proposed.

  8. Retention prediction of a set of amino acids under gradient elution conditions in hydrophilic interaction liquid chromatography.

    PubMed

    Gika, Helen; Theodoridis, Georgios; Mattivi, Fulvio; Vrhovsek, Urska; Pappa-Louisi, Adriani

    2012-02-01

    The analysis of amino acids presents significant challenges to contemporary analytical separations. The present paper investigates the possibility of retention prediction in hydrophilic interaction chromatography (HILIC) gradient elution based on the analytical solution of the fundamental equation of the multilinear gradient elution derived for reversed-phase systems. A simple linear dependence of the logarithm of the solute retention (ln k) upon the volume fraction of organic modifier (φ) in a binary aqueous-organic mobile is adopted. Utility of the developed methodology was tested on the separation of a mixture of 21 amino acids carried out with 14 different gradient elution programs (from simple linear to multilinear and curved shaped) using ternary eluents in which a mixture of methanol and water (1:1, v/v) was the strong eluting member and acetonitrile was the weak solvent. Starting from at least two gradient runs, the prediction of solute retention obtained under all the rest gradients was excellent, even when curved gradient profiles were used. Development of such methodologies can be of great interest for a wide range of applications.

  9. Immunoglobulin G elution in protein A chromatography employing the method of chromatofocusing for reducing the co-elution of impurities.

    PubMed

    Pinto, Nuno D S; Uplekar, Shaunak D; Moreira, Antonio R; Rao, Govind; Frey, Douglas D

    2017-01-01

    Purification processes for monoclonal Immunoglobulin G (IgG) typically employ protein A chromatography as a capture step to remove most of the impurities. One major concern of the post-protein A chromatography processes is the co-elution of some of the host cell proteins (HCPs) with IgG in the capture step. In this work, a novel method for IgG elution in protein A chromatography that reduces the co-elution of HCPs is presented where a two-step pH gradient is self-formed inside a protein A chromatography column. The complexities involved in using an internally produced pH gradient in a protein A chromatography column employing adsorbed buffering species are discussed though equation-based modeling. Under the conditions employed, ELISA assays show a 60% reduction in the HCPs co-eluting with the IgG fraction when using the method as compared to conventional protein A elution without affecting the IgG yield. Evidence is also obtained which indicates that the amount of leached protein A present in free solution in the purified product is reduced by the new method. Biotechnol. Bioeng. 2017;114: 154-162. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  10. 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

  11. Cation exchange chromatographic elution and separation of rubidium

    SciTech Connect

    Mehta, V.P.; Khopkar, S.M.

    1982-01-01

    The systematic cation exchange chromatographic separation of rubidium on Dowex 50W-X8 was carried out with mineral acids and their salts as eluants.A selectivity scale for various eluants in terms of the elution constant was devised. Rubidium was separated from a large number of elements in binary mixtures by the process of gradient or selective elutions or selective sorption. The noteworthy feature of the method is the sequential separation of rubidium from alkali as well as alkaline earth elements.

  12. Biodegradable Polymer-Based Sirolimus-Eluting Stents With Differing Elution and Absorption Kinetics: The PANDA III Trial.

    PubMed

    Xu, Bo; Gao, Runlin; Yang, Yuejin; Cao, Xuebin; Qin, Lei; Li, Yi; Li, Zhanquan; Li, Xueqi; Lin, Hailong; Guo, Yong; Ma, Yitong; Wang, Jian'an; Nie, Shaoping; Xu, Liang; Cao, Eric; Guan, Changdong; Stone, Gregg W

    2016-05-17

    Whether the rate of drug elution and polymer absorption affects clinical outcomes of biodegradable polymer-based drug-eluting stents (DES) is unknown. The widely used polylactide polymer-based Excel stent (JW Medical, Weihai, China) elutes sirolimus within 180 days, and the polylactide polymer is completely absorbed within 6 to 9 months. In contrast, the poly-lactide-co-glycolide polymer-based BuMA stent (Sino Medical, Tianjin, China) elutes sirolimus within 30 days, and the poly-lactide-co-glycolide polymer is completely absorbed within 3 months. Thus, both metallic DES elute sirolimus, isolating major differences to the polymer and elution kinetics. The goal of this study was to compare the safety and effectiveness between the BuMA sirolimus-eluting stent (SES) and Excel SES in an "all-comers" population. PANDA III was a multicenter trial with few exclusion criteria, powered for sequential noninferiority and superiority testing. The primary endpoint was 1-year target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. Between December 2013 and August 2014, 2,348 patients were randomly assigned to treatment with BuMA (n = 1,174) or Excel SES (n = 1,174). The 1-year primary endpoint of TLF occurred in 6.4% of patients in each group (difference: 0.06%; 95% confidence interval: 1.93% to 2.04%; pnoninferiority = 0.0003; psuperiority = 0.95). There were no significant between-group differences in any of the secondary endpoints other than the incidence of definite/probable stent thrombosis, which occurred less frequently with the BuMA stent (0.5% vs. 1.3%; log-rank p = 0.048). The BuMA SES was demonstrated to be noninferior to the Excel SES for 1-year TLF, with a lower incidence of stent thrombosis. (Comparison of BuMA eG Based BioDegradable Polymer Stent With EXCEL Biodegradable Polymer Sirolimus-eluting Stent in "Real-World" Practice [PANDA-III]; NCT02017275). Copyright

  13. Development of a pheromone elution rate physical model

    USDA-ARS?s Scientific Manuscript database

    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...

  14. Biodegradable Cable-Tie Rapamycin-eluting Stents.

    PubMed

    Lee, Cheng-Hung; Hsieh, Ming-Jer; Chang, Shang-Hung; Chiang, Chang-Lin; Fan, Ching-Lung; Liu, Shih-Jung; Chen, Wei-Jan; Wang, Chao-Jan; Hsu, Ming-Yi; Hung, Kuo-Chun; Chou, Chung-Chuan; Chang, Po-Cheng

    2017-03-08

    "Cable-tie" type biodegradable stents with drug-eluting nanofiber were developed to treat rabbit denuded arteries in this study. Biodegradable stents were fabricated using poly-L-lactide film following being cut and rolled into a cable-tie type stent. Additionally, drug-eluting biodegradable nanofiber tubes were electrospun from a solution containing poly (lactic-co-glycolic acid), rapamycin, and hexafluoroisopropanol, and then mounted onto the stents. The fabricated rapamycin-eluting cable-tie stents exhibited excellent mechanical properties on evaluation of compression test and collapse pressure, and less than 8% weight loss following being immersed in phosphate-buffered saline for 16 weeks. Furthermore, the biodegradable stents delivered high rapamycin concentrations for over 4 weeks and achieved substantial reductions in intimal hyperplasia associated with elevated heme oxygenase-1 and calponin level on the denuded rabbit arteries during 6 months of follow-up. The drug-eluting cable-tie type stents developed in this study might have high potential impacts for the local drug delivery to treat various vascular diseases.

  15. Development of a pheromone elution rate physical model

    Treesearch

    M.E. Teske; H.W. Thistle; B.L. Strom; H. Zhu

    2015-01-01

    A first principle modeling approach has been applied to available data describing the elution of semiochemicals from pheromone dispensers. These data included field data for 27 products developed by several manufacturers, including homemade devices, as well as environmental chamber data collected on three semiochemical products. The goal of this effort was to...

  16. Meningitis and a safe dexamethasone-eluting intracochlear electrode array.

    PubMed

    Stathopoulos, Dimitra; Chambers, Scott; Adams, Louise; Robins-Browne, Roy; Miller, Christopher; Enke, Ya Lang; Wei, Benjamin P C; O'Leary, Stephen; Cowan, Robert; Newbold, Carrie

    2015-07-01

    To evaluate the potential risk of pneumococcal meningitis associated with the use of a dexamethasone-eluting intracochlear electrode array as compared with a control array. In two phases, adult Hooded-Wistar rats were implanted via the middle ear with an intracochlear array and were inoculated with Streptococcus pneumoniae 5 days post-surgery. Phase I created a dosing curve by implanting five groups (n = 6) with a control array, then inoculating 5 days later with different numbers of S. pneumoniae: 0 CFU, 10(3) CFU, 10(4) CFU, 10(4) CFU repeated, or 10(5) CFU (colony forming units). A target infection rate of 20% was aimed for and 10(4) CFU was the closest to this target with 33% infection rate. In phase II, we implanted two groups (n = 10), one with a dexamethasone-eluting array, the other a control array, and both groups were inoculated with 10(4) CFU of S. pneumoniae 5 days post-surgery. The dexamethasone-eluting array group had a 40% infection rate; the control array group had a 60% infection rate. This difference was not statistically significant with a P value of ≥0.5. The use of a dexamethasone-eluting intracochlear electrode array did not increase the risk of meningitis in rats when inoculated with S. pneumoniae via the middle ear 5 days following implantation.

  17. Current manufacturing processes of drug-eluting sutures.

    PubMed

    Champeau, Mathilde; Thomassin, Jean-Michel; Tassaing, Thierry; Jérôme, Christine

    2017-02-24

    Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Drug-eluting sutures represent the next generation of surgical sutures since they fulfill their mechanical functions but also deliver the drug in their vicinity after implantation. These implants are produced by a variety of manufacturing processes. Two general approaches can be followed: (i) the ones that add the API into the material during the manufacturing process of the suture and (ii) the ones that load the API to an already manufactured suture. Areas covered: This review provides an overview of the current manufacturing processes for drug-eluting suture production and discusses their benefits and drawbacks depending on the type of drugs. The mechanical properties and the drug delivery profile of drug-eluting sutures are highlighted since these implants must fulfill both criteria. Expert opinion: For limited drug contents, melt extrusion and electrospinning are the emerging processes since the drug is added during the suture manufacture process. Advantageously, the drug release profile can be tuned by controlling the processing parameters specific to each process and the composition of the drug-containing polymer. If high drug content is targeted, the coating or grafting of a drug layer on a pre-manufactured suture allows for preservation of the tensile strength requirements of the suture.

  18. Nonideal Sorption-Desorption and Extensive Elution Tailing

    NASA Astrophysics Data System (ADS)

    Russo, A. E.; Akyol, N. H.; Schnaar, G. A.; Johnson, G. R.; Yolcubal, I.; Brusseau, M. L.

    2011-12-01

    Contamination of subsurface environments by organic compounds continues to pose a risk to the environment. Sorption is a critical process that influences the transport and fate of organic contaminants. Contaminant mobility, bioavailability, and the effectiveness of remediation efforts are mediated in part by sorption/desorption processes. Miscible-displacement experiments were conducted to characterize long-term, low-concentration elution tailing associated with sorption/desorption processes. A variety of soils and aquifer sediments, representing a range of particle-size distributions and organic-carbon contents, were employed, and trichloroethene (TCE) was used as the model organic compound. Trichloroethene transport exhibited extensive elution tailing for all media, with several hundred to several thousand pore volumes of water flushing required to reach the detection limit (~0.1 μg/L). The elution tailing was more extensive for the media with higher organic-carbon contents and associated retardation factors. However, when normalized by retardation, the extent of tailing did not correlate directly to organic-carbon content. These latter results suggest that differences in the geochemical nature of organic carbon (e.g., composition, structure) among the various media influenced observed behavior. A mathematical model incorporating nonlinear, rate-limited sorption/desorption described by a continuous-distribution function was used to successfully simulate trichloroethene transport, including the extensive elution tailing.

  19. 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

    2013-02-08

    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.

  20. Simultaneous determination of AMN107 and Imatinib (Gleevec, Glivec, STI571) in cultured tumour cells using an isocratic high-performance liquid chromatography procedure with UV detection.

    PubMed

    Guetens, Gunther; Prenen, Hans; De Boeck, Gert; van Oosterom, Allan; Schöffski, Patrick; Highley, Martin; de Bruijn, Ernst A

    2007-02-01

    A reversed phase high-performance liquid chromatographic (HPLC) method with UV detection was developed for the simultaneous determination of imatinib (Gleevec, Glivec, STI571) and AMN107 in cultured tumour cells, using clozapine as an internal standard. The compounds of interest were extracted by liquid-liquid extraction using TOXI-TUBES((R)) A extraction tubes. Chromatographic separation was performed on a Phenomenex Gemini C18 reversed phase column (150 mm x 2.0 mm, 5 microm particle size), using a mixture of 65% CH(3)OH (methanol) and 35% NH(4)Ac (Ammonium acetate) buffer (20mM, pH 10). Separation was achieved under isocratic conditions at a flow rate of 0.5 ml/min. Imatinib, clozapine and AMN107 are detected by UV detection at 260 nm. Calibration curves were linear from 50 to 7500 ng/ml with correlation coefficients (r(2)) better than 0.998. The limit of quantitation (LOD) was 50 ng/ml. The method has been successfully applied to a cellular kinetics study.

  1. 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.

  2. Simultaneous determination of active ingredients in an ophthalmic solution by isocratic tandem-mode HPLC connected reverse phase column and strong cation exchange column.

    PubMed

    Marunouchi, Takahiro; Ono, Masaki; Nakajima, Toshiaki; Ito, Yuji; Aketo, Takao

    2006-02-13

    A tandem-mode high performance liquid chromatography (HPLC) system is described here, which employs reversed phase liquid chromatography (RPLC) followed by strong cation exchange liquid chromatography (SCX), was used to determine the mixture of six ingredients in an ophthalmic solution. As a result of investigations, isocratic HPLC methods that using two columns in tandem-mode; Atlantis dC18 (75 mm x 4.6 mm i.d., 3 microm, ODS) and CAPCELL PAK SCX UG80 (75 mm x 4.6 mm i.d., SCX), which have different separation modes, and control of mixture of methanol/ammonium dihydrogenphosphate buffer as used for the eluent, allowed for six target ingredients to be determined simultaneously. And all ingredients separated perfectly and were determined efficiently and rapidly. Validation of the method was accomplished with respect to linearity (r>0.999), recovery (99.4-100.4%), precision (R.S.D. 0.1-0.9%) and specificity. These results suggest that the fusion of different separation modes can be used for the simultaneous determination of ingredients in ophthalmic solutions, and this can be accomplished rapidly and with high precision.

  3. 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

  4. A resorbable antibiotic eluting bone void filler for periprosthetic joint infection prevention.

    PubMed

    Jones, Zachary; Brooks, Amanda E; Ferrell, Zachary; Grainger, David W; Sinclair, Kristofer D

    2016-11-01

    Periprosthetic joint infection (PJI) following total knee arthroplasty is a globally increasing procedural complication. These infections are difficult to treat and typically require revision surgery. Antibiotic-loaded bone cement is frequently utilized to deliver antibiotics to the site of infection; however, bone cement is a nondegrading foreign body and known to leach its antibiotic load, after an initial burst release, at subtherapeutic concentrations for months. This work characterized a resorbable, antibiotic-eluting bone void filler designed to restore bone volume and prevent PJI. Three device formulations were fabricated, consisting of different combinations of synthetic inorganic bone graft material, degradable polymer matrices, salt porogens, and antibiotic tobramycin. These formulations were examined to determine the antibiotic's elution kinetics and bactericidal potential, the device's degradation in vitro, as well as osteoconductivity and device resorption in vivo using a pilot rabbit bone implant model. Kirby-Bauer antibiotic susceptibility tests assessed bactericidal activity. Liquid chromatography with tandem mass spectrometry measured antibiotic elution kinetics, and scanning electron microscopy was used to qualitatively assess degradation. Results indicated sustained antibiotic release from all three formulations above the Staphylococcus aureus minimum inhibitory concentration for a period of 5 to 8 weeks. Extensive degradation was observed with the Group 3 formulation after 90 days in phosphate-buffered saline, with a lesser degree of degradation observed in the other two formulations. Results from the pilot rabbit study showed the Group 3 device to be biocompatible, with minimal inflammatory response and no fibrous encapsulation in bone. The device was also highly osteoconductive-exhibiting an accelerated mineral apposition rate. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1632-1642, 2016.

  5. Clinical outcomes of chronic kidney disease patients treated with everolimus-eluting stents (EES) and paclitaxel-eluting stents (PES).

    PubMed

    Kitasato, Lisa; Shimohama, Takao; Ikeda, Yuki; Namba, Sayaka; Hashikata, Takehiro; Kameda, Ryo; Sato, Nobuhiro; Takeuchi, Ichiro; Yamaoka-Tojo, Minako; Tojo, Taiki; Ako, Junya

    2015-05-01

    The target lesion revascularization of paclitaxel-eluting stents (PES) has been reported to be lower than that of sirolimus-eluting stents in patients on hemodialysis (HD). However, the comparison of PES and second generation drug-eluting stents in CKD patients has not been fully investigated. We compared clinical outcomes of everolimus-eluting stents (EES) and PES in CKD patients. Hundred and forty seven CKD patients (eGFR<60mLmin(-1)1.73m(-2)) treated with PES (n=74, from May 2007 to December 2009) and EES (n=73, from January 2010 to January 2013) were enrolled in the study. Major adverse cardiac events (MACEs) were defined as death, non-fatal myocardial infarction, and ischemia driven target lesion revascularization. The incidence of 36-month MACE was significantly lower in EES, non-HD group compared to PES, non HD group (0% in EES group and 13.5% in PES group, respectively, P<0.01). There was no significant difference in MACE between EES and PES in HD patients (5.4% in PES group and 5.5% in EES group, P=0.98). In multivariate analysis, PES group and PES ISR were independent factors for worse incidence of MACE. In CKD patients, PES was associated with worse clinical outcomes in non-HD patients as compared with EES. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. 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

  7. Safety and efficacy of a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent.

    PubMed

    Zhu, Jinzhou; Liu, Huizhu; Cui, Haipo; Tang, Zhirong; Song, Chengli; Zhang, Ruiyan

    2017-03-01

    Late stent thrombosis (LST) following drug-eluting stent (DES) implantation in patients with coronary artery disease (CAD) is often associated with delayed vascular healing, resulting from vascular inflammation and hypersensitivity to durable polymers and drugs. Therefore, DES design, materials, and coatings have been technologically revolutionized. Herein, we designed a novel abluminal groove-filled biodegradable polymer sirolimus-eluting stent (AGF-BP-SES), with a sirolimus content of only about one-third of traditional DES. The mechanical performances of AGF-BP-SES during compression and expansion were investigated. The pharmacokinetic (PK) profile of sirolimus was studied in the swine model. The in vivo efficacy of AGF-BP-SES was compared with that of Xience PRIME(®) stent. The results showed that AGF-BP-SES exhibited mechanical properties similar to traditional DES, including the rebound ratio of radial contraction/direction, rebound ratio of axial contraction/direction, and inhomogeneity of compression/expansion. Despite utilizing a reduced dose of sirolimus, AGF-BP-SES delivered sirolimus to the coronary artery in a controlled and efficient manner. The stent maintained a safe and effective local drug concentration without local or systemic risks. In the swine model, histopathological indicators predicted safety and biocompatibility of AGF-BP-SES. In conclusion, AGF-BP-SES maintained similar mechanical properties as other stents while reducing the drug-loading capacity, and showed a favorable safety and efficacy profile of the targeted DES.

  8. Poly(ethylene carbonate): a thermoelastic and biodegradable biomaterial for drug eluting stent coatings?

    PubMed

    Unger, F; Westedt, U; Hanefeld, P; Wombacher, R; Zimmermann, S; Greiner, A; Ausborn, M; Kissel, T

    2007-02-26

    A first feasibility study exploring the utility of poly(ethylene carbonate) (PEC) as coating material for drug eluting stents under in vitro conditions is reported. PEC (Mw 242 kDa, Mw/Mn=1.90) was found to be an amorphous polymer with thermoelastic properties. Tensile testing revealed a stress to strain failure of more than 600%. These properties are thought to be advantageous for expanding coated stents. In vitro cytotoxicity tests showed excellent cytocompatibility of PEC. Based on these findings, a new stenting concept was suggested, pre-coating a bare-metal stent with PPX-N as non-biodegradable basis and applying a secondary PEC coating using an airbrush method. After manual expansion, no delamination or destruction of the coating could be observed using scanning electron microscopy. The surface degradation-controlled release mechanism of PEC may provide the basis for "on demand" drug eluting stent coatings, releasing an incorporated drug predominantly at an inflamed implantation site upon direct contact with superoxide-releasing macrophages. As a release model, metal plates of a defined size and area were coated under the same conditions as the stents with PEC containing radiolabelled paclitaxel. An alkaline KO(2-) solution served as a superoxide source. Within 12 h, 100% of the incorporated paclitaxel was released, while only 20% of the drug was released in non-superoxide releasing control buffer within 3 weeks.

  9. 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

  10. Late coronary thrombosis in paclitaxel-eluting stents. Case reports.

    PubMed

    Cassin, Matteo; De Biasio, Marzia; Macor, Franco; Burelli, Claudio; Vendrametto, Fauzia; Driussi, Mauro; Nicolosi, Gian Luigi

    2007-04-01

    Drug-eluting stent (DES) implantation has reduced angiographic and clinical restenosis that actually develops in less than 10% of treated patients. DESs also tend to delay the endothelialisation process increasing the risk of stent thrombosis. Subacute stent thrombosis may complicate long-term success of coronary angioplasty; it is a sudden event and usually causes acute myocardial infarction or sudden cardiac death. Patients undergoing DES implantation should be treated with dual antiplatelet therapy for at least 3-6 months. We describe two cases presenting with ST-elevation acute myocardial infarction due to stent thrombosis that occurred late after deployment of a paclitaxel-eluting stent, after discontinuation of antiplatelet therapy. It is important, for clinical cardiologists and general practitioners, to know the potential risk of late thrombosis of DES patients and, consequently, the implications regarding management of antiplatelet therapy.

  11. Determination of oxytocin in biological samples by isocratic high-performance liquid chromatography with coulometric detection using C18 solid-phase extraction and polyclonal antibody-based immunoaffinity column purification.

    PubMed

    Kukucka, M A; Misra, H P

    1994-03-04

    A specific high-performance liquid chromatographic (HPLC) method is described for the reliable quantitation of oxytocin using culture media supernatants. The procedure employs solid-phase extraction, antibody-based immunoaffinity purification and isocratic HPLC with dual channel coulometric detection (ED). The lower limit of detection for this cyclic nonapeptide was 40 pg (40 fmol). Due to its relative simplicity, specificity and precision, the HPLC-ED of oxytocin is an accurate and attractive alternative to many existing quantitative methods.

  12. Fast non-aqueous reversed-phase liquid chromatography separation of triacylglycerol regioisomers with isocratic mobile phase. Application to different oils and fats.

    PubMed

    Tamba Sompila, Arnaud W G; Héron, Sylvie; Hmida, Dorra; Tchapla, Alain

    2017-01-15

    The distribution of fatty acid species at the sn-1/3 position or the sn-2 position of triacylglycerols (TAGs) in natural fats and oils affects their physical and nutritional properties. In fats and oils, determining the presence of one or two regioisomers and the identification of structure, where they do have one, as well as their separation, became a problem of fundamental importance to solve. A variety of instrumental technics has been proposed, such as MS, chromatography-MS or pure chromatography. A number of studies deal with the optimization of the separation, but very often, they are expensive in time. In the present study, in order to decrease the analysis time while maintaining good chromatographic separation, we tested different monomeric and polymeric stationary phases and different chromatographic conditions (mobile phase composition and analysis temperature) using Non-Aqueous Reversed Phase Liquid Chromatography (NARP-LC). It was demonstrated that mixed polymeric stationary bonded silica with accessible terminal hydroxyl groups leads to very good separation for the pairs of TAGs regioisomers constituted by two saturated and one unsaturated fatty acid (with double bond number: from 1 to 6). A Nucleodur C18 ISIS percolated by isocratic mobile phase (acetonitrile/2-propanol) at 18°C leads to their separations in less than 15min. The difference of retention times between two regioisomers XYX and XXY are large enough to confirm, as application, the presence of POP, SOP, SOS and PLP and no PPO, SPO, SSO and PPL in Theobroma cacao butter. In the same way, this study respectively shows the presence of SOS, SOP and no SSO, PSO in Butyrospermum parkii butter, POP, SOP, SOS and no PPO, PSO and SSO in Carapa oil and finally POP and no PPO in Pistacia Lentiscus oil.

  13. Fully bioresorbable drug-eluting coronary scaffolds: A review.

    PubMed

    Charpentier, Emmanuel; Barna, Alexandre; Guillevin, Loïc; Juliard, Jean-Michel

    2015-01-01

    Following the development of stents, then drug-eluting stents (DES), bioresorbable scaffolds are proposed as a third evolution in coronary angioplasty, aiming to reduce the incidence of restenosis and stent thrombosis and to restore vascular physiology. At least 16 such devices are currently under development, but published clinical data were available for only three of them in September 2014. The first device is Abbott's BVS(®), a poly-L-lactic acid (PLLA)-based everolimus-eluting device, which has been tested in a registry and two non-randomized trials. Clinical results seem close to what is expected from a modern DES, but possibly with more post-procedural side-effects. Two randomized trials versus DES are underway. This device is already marketed in many European countries. The second device is Elixir's DESolve(®), a PLLA-based novolimus-eluting device, which has been evaluated in two single-arm trials. Results are not widely different from those expected from a DES. The third device is Biotronik's DREAMS(®), a metallic magnesium-based paclitaxel-eluting device, which has been assessed in an encouraging single-arm trial; its second version is currently undergoing evaluation in a single-arm trial. The available results suggest that the technological and clinical development of bioresorbable scaffolds is not yet complete: their possible clinical benefits are still unclear compared with third-generation DES; the impact of arterial physiology restoration has to be assessed over the long term; and their cost-effectiveness has to be established. From the perspective of a health technology assessment, there is no compelling reason to hasten the clinical use of these devices before the results of ongoing randomized controlled trials become available.

  14. 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.

  15. Correlation of characteristic thermal constant and elution temperature in GC.

    PubMed

    Blumberg, L M; Klee, M S

    2001-02-01

    In a temperature-programmed analysis, the solutes that elute at higher temperatures have generally larger characterisitic thermal constants, theta(char). The change approximately matches the temperature-related increase in a carrier gas viscosity. Accounting for the effect allows reduction in the uncertainty of prediction of theta(char) by a factor or f approximately 2 and, in a constant-pressure mode, description of a linear heating ramp by the same dimensionless rate for all solutes.

  16. Concentration effects on peptide elution from pendant PEO layers

    PubMed Central

    Wu, Xiangming; Ryder, Matthew P.; McGuire, Joseph; Schilke, Karl F.

    2014-01-01

    In earlier work, we have provided direction for development of responsive drug delivery systems based on modulation of structure and amphiphilicity of bioactive peptides entrapped within pendant polyethylene oxide (PEO) brush layers. Amphiphilicity promotes retention of the peptides within the hydrophobic inner region of the PEO brush layer. In this work, we describe the effects of peptide surface density on the conformational changes caused by peptide-peptide interactions, and show that this phenomenon substantially affects the rate and extent of peptide elution from PEO brush layers. Three cationic peptides were used in this study: the arginine-rich amphiphilic peptide WLBU2, the chemically identical but scrambled peptide S-WLBU2, and the non-amphiphilic homopolymer poly-L-arginine (PLR). Circular dichroism (CD) was used to evaluate surface density effects on the structure of these peptides at uncoated (hydrophobic) and PEO-coated silica nanoparticles. UV spectroscopy and a quartz crystal microbalance with dissipation monitoring (QCM-D) were used to quantify changes in the extent of peptide elution caused by those conformational changes. For amphiphilic peptides at sufficiently high surface density, peptide-peptide interactions result in conformational changes which compromise their resistance to elution. In contrast, elution of a non-amphiphilic peptide is substantially independent of its surface density, presumably due to the absence of peptide-peptide interactions. The results presented here provide a strategy to control the rate and extent of release of bioactive peptides from PEO layers, based on modulation of their amphiphilicity and surface density. PMID:24780434

  17. Concentration effects on peptide elution from pendant PEO layers.

    PubMed

    Wu, Xiangming; Ryder, Matthew P; McGuire, Joseph; Schilke, Karl F

    2014-06-01

    In earlier work, we have provided direction for development of responsive drug delivery systems based on modulation of structure and amphiphilicity of bioactive peptides entrapped within pendant polyethylene oxide (PEO) brush layers. Amphiphilicity promotes retention of the peptides within the hydrophobic inner region of the PEO brush layer. In this work, we describe the effects of peptide surface density on the conformational changes caused by peptide-peptide interactions, and show that this phenomenon substantially affects the rate and extent of peptide elution from PEO brush layers. Three cationic peptides were used in this study: the arginine-rich amphiphilic peptide WLBU2, the chemically identical but scrambled peptide S-WLBU2, and the non-amphiphilic homopolymer poly-l-arginine (PLR). Circular dichroism (CD) was used to evaluate surface density effects on the structure of these peptides at uncoated (hydrophobic) and PEO-coated silica nanoparticles. UV spectroscopy and a quartz crystal microbalance with dissipation monitoring (QCM-D) were used to quantify changes in the extent of peptide elution caused by those conformational changes. For amphiphilic peptides at sufficiently high surface density, peptide-peptide interactions result in conformational changes which compromise their resistance to elution. In contrast, elution of a non-amphiphilic peptide is substantially independent of its surface density, presumably due to the absence of peptide-peptide interactions. The results presented here provide a strategy to control the rate and extent of release of bioactive peptides from PEO layers, based on modulation of their amphiphilicity and surface density. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Advances in below-the-knee drug-eluting balloons.

    PubMed

    Ferraresi, R; Centola, M; Biondi-Zoccai, G

    2012-04-01

    The management of critical limb ischemia due to below-the-knee disease remains challenging due to the frequent patient comorbidities, diffuse vascular involvement, and high rates of restenosis and disease progression. The BASIL study has established the substantial equivalence between bypass surgery and percutaneous transluminal angioplasty in this setting, at least at mid-term follow-up, but percutaneous techniques and devices have seen major developments since the publication of this pivotal trial in 2005. A major breakthrough has indeed been the introduction of drug-eluting balloons, which have several theoretical advantages in comparison to standard balloons and metallic stents for infra-popliteal lesions. Two clinical trials have already been reported with favorable results for the In.Pact Amphirion paclitaxel-eluting balloon, when employed for below-the-knee lesions. We hereby discuss the rationale for the use of drug-eluting balloons in this complex setting and the main findings of the study by Schmidt et al. and the DEBATE-BTK trial.

  19. Metal elution from Ni- and Fe-based alloy reactors under hydrothermal conditions.

    PubMed

    Faisal, Muhammad; Quitain, Armando T; Urano, Shin-Ya; Daimon, Hiroyuki; Fujie, Koichi

    2004-05-20

    Elution of metals from Ni- and Fe-based alloy (i.e. Inconel 625 and SUS 316) under hydrothermal conditions was investigated. Results showed that metals could be eluted even in a short contact time. At subcritical conditions, a significant amount of Cr was extracted from SUS 316, while only traces of Ni, Fe, Mo, and Mn were eluted. In contrast, Ni was removed in significant amounts compared to Cr when Inconel 625 was tested. Several factors including temperature and contact time were found to affect elution behavior. The presence of air in the fluid even promoted elution under subcritical conditions.

  20. Everolimus-Eluting Bioresorbable Scaffolds for Coronary Artery Disease.

    PubMed

    Ellis, Stephen G; Kereiakes, Dean J; Metzger, D Christopher; Caputo, Ronald P; Rizik, David G; Teirstein, Paul S; Litt, Marc R; Kini, Annapoorna; Kabour, Ameer; Marx, Steven O; Popma, Jeffrey J; McGreevy, Robert; Zhang, Zhen; Simonton, Charles; Stone, Gregg W

    2015-11-12

    In patients with coronary artery disease who receive metallic drug-eluting coronary stents, adverse events such as late target-lesion failure may be related in part to the persistent presence of the metallic stent frame in the coronary-vessel wall. Bioresorbable vascular scaffolds have been developed to attempt to improve long-term outcomes. In this large, multicenter, randomized trial, 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an everolimus-eluting bioresorbable vascular (Absorb) scaffold (1322 patients) or an everolimus-eluting cobalt-chromium (Xience) stent (686 patients). The primary end point, which was tested for both noninferiority (margin, 4.5 percentage points for the risk difference) and superiority, was target-lesion failure (cardiac death, target-vessel myocardial infarction, or ischemia-driven target-lesion revascularization) at 1 year. Target-lesion failure at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7 percentage points; 95% confidence interval, -0.5 to 3.9; P=0.007 for noninferiority and P=0.16 for superiority). There was no significant difference between the Absorb group and the Xience group in rates of cardiac death (0.6% and 0.1%, respectively; P=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; P=0.18), or ischemia-driven target-lesion revascularization (3.0% and 2.5%, respectively; P=0.50). Device thrombosis within 1 year occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13). In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting cobalt-chromium stent, was within the prespecified margin for noninferiority with respect to target-lesion failure at 1 year. (Funded by Abbott Vascular; ABSORB III Clinical

  1. Organ transplantation and drug eluting stents: Perioperative challenges

    PubMed Central

    Dalal, Aparna

    2016-01-01

    Patients listed for organ transplant frequently have severe coronary artery disease (CAD), which may be treated with drug eluting stents (DES). Everolimus and zotarolimus eluting stents are commonly used. Newer generation biolimus and novolimus eluting biodegradable stents are becoming increasingly popular. Patients undergoing transplant surgery soon after the placement of DES are at increased risk of stent thrombosis (ST) in the perioperative period. Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor such as clopidogrel, prasugrel and ticagrelor is instated post stenting to decrease the incident of ST. Cangrelor has recently been approved by Food and Drug Administration and can be used as a bridging antiplatelet drug. The risk of ischemia vs bleeding must be considered when discontinuing or continuing DAPT for surgery. Though living donor transplant surgery is an elective procedure and can be optimally timed, cadaveric organ availability is unpredictable, therefore, discontinuation of antiplatelet medication cannot be optimally timed. The type of stent and timing of transplant surgery can be of utmost importance. Many platelet function point of care tests such as Light Transmittance Aggregrometry, Thromboelastography Platelet Mapping, VerifyNow, Multiple Electrode Aggregrometry are used to assess bleeding risk and guide perioperative platelet transfusion. Response to allogenic platelet transfusion to control severe intraoperative bleeding may differ with the antiplatelet drug. In stent thrombosis is an emergency where management with either a drug eluting balloon or a DES has shown superior outcomes. Post-transplant complications often involved stenosis of an important vessel that may need revascularization. DES are now used for endovascular interventions for transplant orthotropic heart CAD, hepatic artery stenosis post liver transplantation, transplant renal artery stenosis following kidney transplantation, etc. Several antiproliferative drugs

  2. Drug-eluting embolic microspheres for local drug delivery - State of the art.

    PubMed

    Fuchs, Katrin; Duran, Rafael; Denys, Alban; Bize, Pierre E; Borchard, Gerrit; Jordan, Olivier

    2017-09-28

    Embolic microspheres or beads used in transarterial chemoembolization are an established treatment method for hepatocellular carcinoma patients. The occlusion of the tumor-feeding vessels by intra-arterial injection of the beads results in tumor necrosis and shrinkage. In this short review, we describe the utility of using these beads as devices for local drug delivery. We review the latest advances in the development of non-biodegradable and biodegradable drug-eluting beads for transarterial chemoembolization. Their capability to load different drugs, such as chemotherapeutics and anti-angiogenic compounds with different physicochemical properties, like charge and hydrophilicity/hydrophobicity, are discussed. We specifically address controlled and sustained drug release from the microspheres, and the resulting in vivo pharmacokinetics in the plasma vs. drug distribution in the targeted tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Determination of metoprolol enantiomers in human plasma and saliva samples utilizing microextraction by packed sorbent and liquid chromatography-tandem mass spectrometry.

    PubMed

    Elmongy, Hatem; Ahmed, Hytham; Wahbi, Abdel-Aziz; Amini, Ahmad; Colmsjö, Anders; Abdel-Rehim, Mohamed

    2016-08-01

    A sensitive, accurate and reliable bioanalytical method for the enantioselective determination of metoprolol in plasma and saliva samples utilizing liquid chromatography-electrospray ionization tandem mass spectrometry was developed and validated. Human plasma and saliva samples were pretreated by microextraction by packed sorbent (MEPS) prior to analysis. A new MEPS syringe form with two inputs was used. Metoprolol enantiomers and internal standard pentycaine (IS) were eluted from MEPS sorbent using isopropanol after removal of matrix interferences using aliquots of 5% methanol in water. Complete separation of metoprolol enantiomers was achieved on a Cellulose-SB column (150 × 4.6 mm, 5 μm) using isocratic elution with mobile phase 0.1% ammonium hydroxide in hexane-isopropanol (80:20, v/v) with a flow rate of 0.8 mL/min. A post-column solvent-assisted ionization was applied to enhance metoprolol ionization signal in positive mode monitoring (+ES) using 0.5% formic acid in isopropanol at a flow rate of 0.2 mL/min. The total chromatographic run time was 10 min for each injection. The detection of metoprolol in plasma and saliva samples was performed using triple quadrupole tandem mass spectrometer in +ES under the following mass transitions: m/z 268.08 → 72.09 for metoprolol and m/z 303.3 → 154.3 for IS. The linearity range was 2.5-500 ng/mL for both R- and S-metoprolol in plasma and saliva. The limits of detection and quantitation for both enantiomers were 0.5 and 2.5 ng/mL respectively, in both matrices (plasma and saliva). The intra- and inter-day precisions were presented in terms of RSD values for replicate analysis of quality control samples and were <5%; the accuracy of determinations varied from 96 to 99%. The method was able to determine the therapeutic levels of metoprolol enantiomers in both human plasma and saliva samples successfully, which can aid in therapeutic drug monitoring in clinical laboratories. Copyright © 2016

  4. 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

  5. Exact peak compression factor in linear gradient elution. I. Theory.

    PubMed

    Gritti, Fabrice; Guiochon, Georges

    2008-11-28

    The only existing expression for the peak compression factor in linear gradient elution chromatography assumes that the linear-solvent-strength model (LSSM) applies to the retention of the compound studied, that the column efficiency is independent of the mobile phase composition, and that, during gradient elution, the relative retention factor of a compound inside its band varies linearly with the distance from the band center. Because the retention factors of many analytes in reversed-phase liquid chromatography do not rigorously follow the LSSM, we extend the theoretical approach of Poppe et al. to the prediction of peak compression factors in linear gradient elution chromatography for any retention model, when column efficiency varies with the mobile phase composition. Only the contribution of the chromatographic column to the peak compression was taken into account, the contribution of the dwell volume being neglected. A second restriction is the linearity of the relative retention factor as a function of the position along the band width inside the column. These constraints could be the sources for the difference observed between experimental and theoretical values of peak compression factors. When the retention factor varies steeply with the mobile phase composition, such as with proteins or large peptides in RP-HPLC, it is found that the thermodynamic compression term, which tends to sharpen the peak, is coupled with the column dispersion term, which tends to broaden the peak. This coupling term acts as an apparent dispersion term, contributing to broaden the peak. This result is consistent with the measurements of peak compression factors found in the literature.

  6. 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

  7. First-in-man use of polymer-free valsartan-eluting stents in small coronary vessels: a comparison to polymer-free rapamycin (2%)-eluting stents.

    PubMed

    Peters, Stefan; Behnisch, Boris; Heilmann, Torsten; Richter, Christian

    2009-06-01

    Orally administered angiotensin receptor antagonists administered after bare-metal stent implantation and even after drug-eluting stent implantation seem to lower in-stent restenosis rates.Whether valsartan-eluting stents are similarly effective was tested here in a first-in-man trial. The efficacy of a polymer-free drug-eluting stent coated with 300 mcg valsartan was compared to a coating with a 2% rapamycin solution in small (eluting stents and 30 patients (24 males, mean age 65.7+/-8.4 years) received YUKON Choice rapamycin-eluting stents. Clopidogrel was given for six months in all patients. Within the first 30 days, no adverse events occurred in either group. Binary in-stent restenosis rate was 30.8% (four in 13 angiographic controls) in the valsartan-eluting stent group and 35.0% (eight in 20 angiographic controls) in the rapamycin-eluting YUKON Choice stent group. Mean late lumen loss was 0.78+/-0.53 mm and 0.79+/-0.58 mm, respectively. Target lesion and target vessel revascularisation rate was 26.6% and 25.0%, respectively. No restenoses in rapamycin-eluting YUKON Choice stents appeared in 12 patients with adjunct oral valsartan administration. If polymer-free YUKON Choice stents are used in small vessels, valsartan-eluting stents show an identical efficacy as rapamycin-loaded stents. In patients with rapamycin-eluting YUKON Choice stents it seems that the efficacy can be increased by oral valsartan administration.

  8. 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.

  9. 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.

  10. Materials technology in drug eluting balloons: Current and future perspectives.

    PubMed

    Xiong, Gordon Minru; Ang, Huiying; Lin, Jinjie; Lui, Yuan Siang; Phua, Jie Liang; Chan, Jing Ni; Venkatraman, Subbu; Foin, Nicolas; Huang, Yingying

    2016-10-10

    The coating material technology is important for the delivery of anti-proliferative drugs from the surface of drug-eluting balloons (DEBs), which are emerging as alternatives to drug-eluting stents (DES) in the field of interventional cardiology. Currently, several shortcomings limit their competition with DES, including low drug transfer efficiency to the arterial tissues and undesirable particulate generation from the coating matrix. In this review, we provide a survey of the materials used in existing DEBs, and discussed the mechanisms of actions of both the drugs and coating materials. The type of drug and the influence of the coating material characteristics on the drug uptake, distribution and retention in arterial tissues are described. We also summarize the novel coating excipients under development and provide our perspective on the possible use of nano-scale carriers to address the shortcomings of current coating technology. The scope of this review includes only materials that have been approved for biomedical applications or are generally recognized as safe (GRAS) for drug delivery.

  11. 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.

  12. 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

  13. Drug- and Gene-eluting Stents for Preventing Coronary Restenosis

    PubMed Central

    Lekshmi, Kamali Manickavasagam; Che, Hui-Lian; Cho, Chong-Su

    2017-01-01

    Coronary artery disease (CAD) has been reported to be a major cause of death worldwide. Current treatment methods include atherectomy, coronary angioplasty (as a percutaneous coronary intervention), and coronary artery bypass. Among them, the insertion of stents into the coronary artery is one of the commonly used methods for CAD, although the formation of in-stent restenosis (ISR) is a major drawback, demanding improvement in stent technology. Stents can be improved using the delivery of DNA, siRNA, and miRNA rather than anti-inflammatory/anti-thrombotic drugs. In particular, genes that could interfere with the development of plaque around infected regions are conjugated on the stent surface to inhibit neointimal formation. Despite their potential benefits, it is necessary to explore the various properties of gene-eluting stents. Furthermore, multifunctional electronic stents that can be used as a biosensor and deliver drug- or gene-based on physiological condition will be a very promising way to the successful treatment of ISR. In this review, we have discussed the molecular mechanism of restenosis, the use of drug- and gene-eluting stents, and the possible roles that these stents have in the prevention and treatment of coronary restenosis. Further, we have explained how multifunctional electronic stents could be used as a biosensor and deliver drugs based on physiological conditions. PMID:28184335

  14. Dynamics of silver elution from functionalised antimicrobial nanofiltration membranes.

    PubMed

    Choudhari, S; Habimana, O; Hannon, J; Allen, A; Cummins, E; Casey, E

    2017-07-01

    In an effort to mitigate biofouling on thin film composite membranes such as nanofiltration and reverse osmosis, a myriad of different surface modification strategies has been published. The use of silver nanoparticles (Ag-NPs) has emerged as being particularly promising. Nevertheless, the stability of these surface modifications is still poorly understood, particularly under permeate flux conditions. Leaching or elution of Ag-NPs from the membrane surface can not only affect the antimicrobial characteristics of the membrane, but could also potentially present an environmental liability when applied in industrial-scale systems. This study sought to investigate the dynamics of silver elution and the bactericidal effect of an Ag-NP functionalised NF270 membrane. Inductively coupled plasma-atomic emission spectroscopy was used to show that the bulk of leached silver occurred at the start of experimental runs, and was found to be independent of salt or permeate conditions used. Cumulative amounts of leached silver did, however, stabilise following the initial release, and were shown to have maintained the biocidal characteristics of the modified membrane, as observed by a higher fraction of structurally damaged Pseudomonas fluorescens cells. These results highlight the need to comprehensively assess the time-dependent nature of bactericidal membranes.

  15. Recent developments in drug eluting devices with tailored interfacial properties.

    PubMed

    Sanchez-Rexach, Eva; Meaurio, Emilio; Sarasua, Jose-Ramon

    2017-05-04

    Drug eluting devices have greatly evolved during past years to become fundamental products of great marketing importance in the biomedical field. There is currently a large diversity of highly specialized devices for specific applications, making the development of these devices an exciting field of research. The replacement of the former bare metal devices by devices loaded with drugs allowed the sustained and controlled release of drugs, to achieve the desired local therapeutic concentration of drug. The newer devices have been "engineered" with surfaces containing micro- and nanoscale features in a well-controlled manner, that have shown to significantly affect cellular and subcellular function of various biological systems. For example, the topography can be structured to form an antifouling surface mimicking the defense mechanisms found in nature, like the skin of the shark. In the case of bone implants, well-controlled nanostructured interfaces can promote osteoblast differentiation and matrix production, and enhance short-term and long-term osteointegration. In any case, the goal of current research is to design implants that induce controlled, guided, and rapid healing. This article reviews recent trends in the development of drug eluting devices, as well as recent developments on the micro/nanotechnology scales, and their future challenges. For this purpose medical devices have been divided according to the different systems of the body they are focused to: orthopedic devices, breathing stents, gastrointestinal and urinary systems, devices for cardiovascular diseases, neuronal implants, and wound dressings. Copyright © 2017. Published by Elsevier B.V.

  16. Drug-eluting fibers for HIV-1 inhibition and contraception.

    PubMed

    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.

  17. Advantages and disadvantages of biodegradable platforms in drug eluting stents

    PubMed Central

    Rodriguez-Granillo, Agustina; Rubilar, Bibiana; Rodriguez-Granillo, Gaston; Rodriguez, Alfredo E

    2011-01-01

    Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to bare-metal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place. Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology. PMID:21499496

  18. Comparison of DNA extraction kits and modification of DNA elution procedure for the quantitation of subdominant bacteria from piggery effluents with real-time PCR.

    PubMed

    Desneux, Jérémy; Pourcher, Anne-Marie

    2014-08-01

    Four commercial DNA extraction kits and a minor modification in the DNA elution procedure were evaluated for the quantitation of bacteria in pig manure samples. The PowerSoil(®), PowerFecal(®), NucleoSpin(®) Soil kits and QIAamp(®) DNA Stool Mini kit were tested on raw manure samples and on lagoon effluents for their ability to quantify total bacteria and a subdominant bacteria specific of pig manure contamination: Lactobacillus amylovorus. The NucleoSpin(®) Soil kit (NS kit), and to a lesser extent the PowerFecal(®) kit were the most efficient methods. Regardless of the kit utilized, the modified elution procedure increased DNA yield in the lagoon effluent by a factor of 1.4 to 1.8. When tested on 10 piggery effluent samples, compared to the QIAamp kit, the NS kit combined with the modified elution step, increased by a factor up to 1.7 log10 the values of the concentration of L. amylovorus. Regardless of the type of manure, the best DNA quality and the highest concentrations of bacteria were obtained using the NS kit combined with the modification of the elution procedure. The method recommended here significantly improved quantitation of subdominant bacteria in manure.

  19. Comparison of DNA extraction kits and modification of DNA elution procedure for the quantitation of subdominant bacteria from piggery effluents with real-time PCR

    PubMed Central

    Desneux, Jérémy; Pourcher, Anne-Marie

    2014-01-01

    Four commercial DNA extraction kits and a minor modification in the DNA elution procedure were evaluated for the quantitation of bacteria in pig manure samples. The PowerSoil®, PowerFecal®, NucleoSpin® Soil kits and QIAamp® DNA Stool Mini kit were tested on raw manure samples and on lagoon effluents for their ability to quantify total bacteria and a subdominant bacteria specific of pig manure contamination: Lactobacillus amylovorus. The NucleoSpin® Soil kit (NS kit), and to a lesser extent the PowerFecal® kit were the most efficient methods. Regardless of the kit utilized, the modified elution procedure increased DNA yield in the lagoon effluent by a factor of 1.4 to 1.8. When tested on 10 piggery effluent samples, compared to the QIAamp kit, the NS kit combined with the modified elution step, increased by a factor up to 1.7 log10 the values of the concentration of L. amylovorus. Regardless of the type of manure, the best DNA quality and the highest concentrations of bacteria were obtained using the NS kit combined with the modification of the elution procedure. The method recommended here significantly improved quantitation of subdominant bacteria in manure. PMID:24838631

  20. Sequential elution liquid chromatography can significantly increase the probability of a successful separation by simultaneously increasing the peak capacity and reducing the separation disorder.

    PubMed

    Socia, Adam; Foley, Joe P

    2014-01-10

    This paper demonstrates that sequential elution liquid chromatography (SE-LC), an approach in which two or more elution modes are employed in series for the separation of two or more groups of compounds, can be used to separate not only weak acids (or weak bases) from neutral compounds, but weak acids and weak bases from neutral compounds (and each other) by the sequential application of either of two types of an extended pH gradient prior to a solvent gradient. It also details a comparison, based on peak capacity and separation disorder, of the probability of success of this approach with the unimodal elution approach taken by conventional column liquid chromatography. For an HPLC peak capacity of 120 and samples of moderate complexity (e.g., 12 components), the probability of success (Rs≥1) increases from 37.9% (HPLC) to 85.8% (SE-LC). Different columns were evaluated for their utility for SE-LC using the following criteria: (1) the prediction of the elution order of the groups based on the degree of ionization of the compounds; and (2) the closeness of the peak shape to the ideal Gaussian distribution. The best columns overall were the Zorbax SB-AQ and Waters XBridge Shield columns, as they provided both between-class and within-class separations of all compounds, as well as the lowest degree of tailing of 4-ethylaniline using the pH 2 to pH 8 gradient.

  1. Very thin strut biodegradable polymer everolimus-eluting and sirolimus-eluting stents versus durable polymer zotarolimus-eluting stents in allcomers with coronary artery disease (BIO-RESORT): a three-arm, randomised, non-inferiority trial.

    PubMed

    von Birgelen, Clemens; Kok, Marlies M; van der Heijden, Liefke C; Danse, Peter W; Schotborgh, Carl E; Scholte, Martijn; Gin, R Melvyn Tjon Joe; Somi, Samer; van Houwelingen, K G; Stoel, M G; de Man, Frits H A F; Louwerenburg, J Hans W; Hartmann, Marc; Zocca, Paolo; Linssen, Gerard C M; van der Palen, Job; Doggen, Carine J M; Löwik, Marije M

    2016-11-26

    In patients with coronary artery disease, treated with durable polymer-coated drug-eluting stents, the life-long presence of the polymer might delay arterial healing. Novel very thin strut biodegradable polymer stents, which leave only a bare metal stent after polymer resorption, might improve long-term outcome. We investigated in allcomers the safety and efficacy of three stents eluting either everolimus, sirolimus, or zotarolimus, often clinically used but never compared, of which the biodegradable polymer everolimus-eluting stent was never before assessed in allcomers. The large-scale, investigator-initiated, multicentre, assessor and patient blinded, three-arm, randomised, BIO-RESORT non-inferiority trial was done at four clinical sites in the Netherlands. All-comer patients were aged 18 years or older, capable of providing informed consent, and required a percutaneous coronary intervention with drug-eluting stent implantation according to clinical guidelines or the operators' judgment. Exclusion criteria were: participation in another randomised drug or device study before reaching the primary endpoint of that study; planned surgery necessitating interruption of dual antiplatelet therapy within the first 6 months; known intolerance to components of the investigational product or medication required; uncertainty about the adherence to follow-up procedures or an assumed life expectancy of less than 1 year; or known pregnancy. Web-based computer-generated allocation sequences randomly assigned patients (1:1:1) to treatment with very thin strut biodegradable polymer everolimus-eluting or sirolimus-eluting stents (which differ substantially in type, amount, distribution, and resorption speed of their respective coating), or thin strut durable polymer zotarolimus-eluting stents. The primary endpoint was a composite of safety (cardiac death or target vessel-related myocardial infarction) and efficacy (target vessel revascularisation) at 12 months of follow up with a

  2. Are drug-eluting stents the future of SFA treatment?

    PubMed

    Bosiers, M; Deloose, K; Keirse, K; Verbist, J; Peeters, P

    2010-02-01

    Drug-eluting stent (DES) technology was developed to prevent early thrombosis and late luminal loss to potentially improve long-term patency rates. Although favorable DES results have recently become available with the Zilver PTX and STRIDES studies, the high price of DES is a major drawback for this technology to become the golden standard for peripheral endovascular therapy in de novo femoro-popliteal (FP) lesions. Nevertheless, DES has the potential to make the difference and to establish itself as an important treatment option in patients presenting with TASC C&D FP lesions who are at high-risk for surgery and for the treatment of in-stent restenosis, where until now, no valuable treatment option has proven to be beneficial.

  3. 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

  4. Development of Absorbable, Antibiotic-Eluting Sutures for Ophthalmic Surgery

    PubMed Central

    Kashiwabuchi, Fabiana; Parikh, Kunal S.; Omiadze, Revaz; Zhang, Shuming; Luo, Lixia; Patel, Himatkumar V.; Xu, Qingguo; Ensign, Laura M.; Mao, Hai-Quan; Hanes, Justin; McDonnell, Peter J.

    2017-01-01

    Purpose To develop and evaluate an antibiotic-eluting suture for ophthalmic surgery. Methods Wet electrospinning was used to manufacture sutures composed of poly(L-lactide), polyethylene glycol (PEG), and levofloxacin. Size, morphology, and mechanical strength were evaluated via scanning electron microscopy and tensile strength, respectively. In vitro drug release was quantified using high performance liquid chromatography. In vitro suture activity against Staphylococcus epidermidis was investigated through bacterial inhibition studies. Biocompatibility was determined via histological analysis of tissue sections surrounding sutures implanted into Sprague-Dawley rat corneas. Results Sutures manufactured via wet electrospinning were 45.1 ± 7.7 μm in diameter and 0.099 ± 0.007 newtons (N) in breaking strength. The antibiotic release profile demonstrated a burst followed by sustained release for greater than 60 days. Increasing PEG in the polymer formulation, from 1% to 4% by weight, improved drug release without negatively affecting tensile strength. Sutures maintained a bacterial zone of inhibition for at least 1 week in vitro and elicited an in vivo tissue reaction comparable to a nylon suture. Conclusions There is a need for local, postoperative delivery of antibiotics following ophthalmic procedures. Wet electrospinning provides a suitable platform for the development of sutures that meet size requirements for ophthalmic surgery and are capable of sustained drug release; however, tensile strength must be improved prior to clinical use. Translational Relevance No antibiotic-eluting suture exists for ophthalmic surgery. A biocompatible, high strength suture capable of sustained antibiotic release could prevent ocular infection and preclude compliance issues with topical eye drops. PMID:28083445

  5. (68)Ga generator integrated system: elution-purification-concentration integration.

    PubMed

    Le, Van So

    2013-01-01

    A (68)Ge/(68)Ga generator combined with an automated (68)Ga eluate purification-concentration unit [radioisotope generator integrated system (RADIGIS)], specially designed for (68)Ga processing (RADIGIS-(68)Ga), was developed. The high-stability sorbents of a nanocrystalline structure Zr-Ti ceramic matrix were used for immobilizing the (68)Ge, and the (68)Ga was eluted from the sorbent column with 3.5 mL 0.05-0.1 M HCl solution following an optimized (68)Ga-elution schedule. The (68)Ge breakthrough <10(-3)% and no (68)Ge zone spreading/drift found in PET imaging of the (68)Ga generator column prove the excellent performance of the sorbents. (68)Ga eluate was purified on a small column of salt-form ion exchange resin using an aqueous alcohol solution mixture of hydrochloric and ascorbic acids, and halide salts. An alkali solution was used for stripping (68)Ga from the ion exchange resin column to obtain a purified (68)Ga solution, which is conditioned with acidic solution to obtain a final (68)Ga product in either 0.75 mL 0.5 M NaCl solution of pH 3-4 or 0.5 M sodium acetate or citrate solution of pH 5. The (68)Ge content in purified (68)Ga solution was <10(-6)%. An insignificant metallic contamination including (68)Zn found in the (68)Ga solution and its alkalinity-acidity were evaluated with respect to (68)Ga radiolabeling efficacy for DOTATATE and DOTATOC ligands. Quality control protocols were also developed to evaluate the quality of (68)Ga solution.

  6. Ultrathin, bioresorbable polymer sirolimus-eluting stents versus thin, durable polymer everolimus-eluting stents in patients undergoing coronary revascularisation (BIOFLOW V): a randomised trial.

    PubMed

    Kandzari, David E; Mauri, Laura; Koolen, Jacques J; Massaro, Joseph M; Doros, Gheorghe; Garcia-Garcia, Hector M; Bennett, Johan; Roguin, Ariel; Gharib, Elie G; Cutlip, Donald E; Waksman, Ron

    2017-08-25

    The development of coronary drug-eluting stents has included use of new metal alloys, changes in stent architecture, and use of bioresorbable polymers. Whether these advancements improve clinical safety and efficacy has not been shown in previous randomised trials. We aimed to examine the clinical outcomes of a bioresorbable polymer sirolimus-eluting stent compared with a durable polymer everolimus-eluting stent in a broad patient population undergoing percutaneous coronary intervention. BIOFLOW V was an international, randomised trial done in patients undergoing elective and urgent percutaneous coronary intervention in 90 hospitals in 13 countries (Australia, Belgium, Canada, Denmark, Germany, Hungary, Israel, the Netherlands, New Zealand, South Korea, Spain, Switzerland, and the USA). Eligible patients were those aged 18 years or older with ischaemic heart disease undergoing planned stent implantation in de-novo, native coronary lesions. Patients were randomly assigned (2:1) to either an ultrathin strut (60 μm) bioresorbable polymer sirolimus-eluting stent or to a durable polymer everolimus-eluting stent. Randomisation was via a central web-based data capture system (mixed blocks of 3 and 6), and stratified by study site. The primary endpoint was 12-month target lesion failure. The primary non-inferiority comparison combined these data from two additional randomised trials of bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent with Bayesian methods. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02389946. Between May 8, 2015, and March 31, 2016, 4772 patients were recruited into the study. 1334 patients met inclusion criteria and were randomly assigned to treatment with bioresorbable polymer sirolimus-eluting stents (n=884) or durable polymer everolimus-eluting stents (n=450). 52 (6%) of 883 patients in the bioresorbable polymer sirolimus-eluting stent group and 41 (10%) of

  7. Determinants of Protein Elution Rates from Preparative Ion-Exchange Adsorbents

    PubMed Central

    Angelo, James M.; Lenhoff, Abraham M.

    2016-01-01

    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 uptake and 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. PMID:26948763

  8. 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.

  9. Safety and Efficacy of New Sirolimus-eluting Stent Models in a Preclinical Study.

    PubMed

    Estévez-Loureiro, Rodrigo; Pérez de Prado, Armando; Pérez-Martínez, Claudia; Cuellas-Ramón, Carlos; Regueiro-Purriños, Marta; Gonzalo-Orden, José M; López-Benito, María; Molina-Crisol, María; Duocastella-Codina, Luis; Fernández-Vázquez, Felipe

    2015-12-01

    Initial preclinical studies are required during the process of improving polymers, platforms, and drug-eluting systems for new coronary stent designs. Our objective was to analyze the efficacy and safety of new drug-eluting stent models compared with a conventional stent and commercialized drug-eluting stents in an experimental model with healthy porcine coronary arteries. Sixty stents (conventional stent, new sirolimus-eluting stents: drug-eluting stents 1, 2 and 3; Cypher(®) and Xience(®)) were randomly placed in the coronary arteries of 20 Large White domestic pigs. Angiographic and histomorphometric studies were done 28 days later. The stents were implanted at a stent/artery ratio of 1.34±0.15, with no significant differences between groups. The new stents showed less late loss and angiographic restenosis than conventional stents (P=.006 and P<.001, respectively). Histologically, restenosis and neointimal area were lower with all the new platforms than with the conventional stents (P<.001 for each variable), and no differences were found vs the drug-eluting stents on the market. Safety data showed that endothelialization was lower with drug-eluting stents than with conventional stents, except for drug-eluting stent 3 (P=.084). Likewise, inflammation was lower with drug-eluting stent 3 than with other stents. The new drug-eluting stent platforms studied are associated with less restenosis than conventional stents and showed no significant differences in safety or efficacy vs commercialized drug-eluting stents. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  10. Two-column sequential injection chromatography--new approach for fast and effective analysis and its comparison with gradient elution chromatography.

    PubMed

    Chocholous, Petr; Satínský, Dalibor; Sklenárová, Hana; Solich, Petr

    2010-05-23

    This work presents novel approach in low-pressure chromatography flow systems--two-column Sequential Injection Chromatography (2-C SIC) and its comparison with gradient elution chromatography on the same instrument. The system was equipped with two different chromatographic columns (connected to selection valve in parallel design) for isocratic separation and determination of all components in composed anti-inflammatory pharmaceutical preparation (tablets). The sample was first injected on the first column of length 30 mm where less retained analytes were separated and then the sample was injected on the second column of length 10 mm where more retained analytes were separated. The SIC system was based on a commercial SIChrom manifold (8-port high-pressure selection valve and medium-pressure syringe pump with 4 mL reservoir) (FIAlab, USA) with two commercially available monolithic columns the "first column" Chromolith Flash RP-18e (25 mm x 4.6 mm i.d. with guard column 5 mm x 4.6 mm i.d.) and the "second column" Chromolith RP-18e (10 mm x 4.6 mm i.d.) and CCD UV-vis detector USB 4000 with micro-volume 1.0 cm Z flow cell. Two mobile phases were used for analysis (one for each column). The mobile phase 1 used for elution of paracetamol, caffeine and salicylic acid (internal standard) was acetonitrile/water (10:90, v/v, the water part of pH 3.5 adjusted with acetic acid), flow rate was 0.9 mL min(-1) (volume 3.0 mL of mobile phase per analysis). The mobile phase 2 used for elution of propyphenazone was acetonitrile/water (30:70, v/v); flow rate was 1.2 mL min(-1) (volume 1.5 mL of mobile phase per analysis). Absorbance was monitored at 210 nm. Samples were prepared by dissolving of one tablet in 30% acetonitrile and 10 microL of filtered supernatant was injected on each column (2 x 10 microL). The chromatographic resolution between all compounds was >1.45 and analysis time was 5.5 min under the optimal conditions. Limits of detection were determined at 0.4 microg m

  11. 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

  12. Nobori-Biolimus-Eluting Stents versus Resolute Zotarolimus-Eluting Stents in Patients Undergoing Coronary Intervention: A Propensity Score Matching

    PubMed Central

    Tantawy, Ayman; Ahn, Chul-Min; Shin, Dong-Ho; Kim, Jung-Sun; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo

    2017-01-01

    Purpose To compare the 1-year outcomes of a durable polymer Zotarolimus-eluting stent (ZES) versus a biodegradable polymer Biolimus-eluting stent (BES) in patients undergoing percutaneous coronary intervention. Materials and Methods A total of 2083 patients from 2 different registries, 1125 treated with BES in NOBORI registry and 858 received ZES in CONSTANT registry were included in this study. Clinical outcomes were compared with the use of propensity score matching (PSM). The primary endpoint was a composite of major adverse cardiovascular and cerebrovascular events (MACCEs) including cardiac death, myocardial infarction, clinically driven target lesion revascularization and stroke. Secondary end points were individual components of MACCEs as well as the incidence of stent thrombosis at 1-year follow-up. Results After PSM, 699 matched pairs of patients (n=1398) showed no significant difference between BES and ZES in the risk of composite MACCEs at 1 year (2.6% vs. 1.7%; p=0.36). Cardiac death was not statistically different between groups (0.7% vs. 0.4%, p=0.73). Target lesion revascularization rate was also similar between BES and ZES (1.1% vs. 0.7%, p=0.579). Non-Q wave myocardial infarction, as well as target-vessel revascularization rate, was similar between the two groups (0.14% for BES and 0.72% for ZES). Both stent types were excellent with no cases of stent thrombosis and rate of Q wave myocardial infarction reported during the follow-up period. Conclusion In this cohort of patients treated with BES or ZES, the rate of MACCEs at 1 year was low and significantly not different between both groups. PMID:28120558

  13. Chemoembolization of Hepatocellular Carcinoma with Drug-Eluting Beads Complicated by Interstitial Pneumonitis

    PubMed Central

    Aladdin, Mohammed; Ilyas, Mohammed

    2011-01-01

    Transarterial chemoembolization has proven benefit in the treatment of unresectable hepatocellular carcinoma (HCC). Commonly reported symptoms following chemoembolization with or without drug-eluting beads include abdominal pain, nausea, and low-grade fever, which typically limited resolve within a few days. A recent study comparing traditional chemoembolization versus chemoembolization with drug-eluting beads demonstrated similar survival between the two techniques, but improved tolerability when the drug-eluting beads were used. This case report describes a patient with unresectable HCC undergoing chemoembolization with drug-eluting beads. The postprocedure course was complicated by interstitial pneumonitis secondary to shunting of the drug-eluting beads containing doxorubicin to both lungs via tumor vasculature. This case highlights the relationship between the number and size of the tumors to be treated, arteriovenous shunting within the liver/tumors, and the size of the embolization particles. PMID:22654266

  14. 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

  15. Mathematical modeling of elution curves for a protein mixture in ion exchange chromatography applied to high protein concentration.

    PubMed

    Orellana, C A; Shene, C; Asenjo, J A

    2009-10-15

    Protein elution curves in ion exchange chromatography (IEC) were simulated with a rate model. Three pure proteins and their mixture were used (alpha-lactalbumin, BSA, and conalbumin) under different operational conditions. The anionic matrix Q-Sepharose FF was used packed in a 1 mL column. A high protein concentration (37.5 mg/mL of total protein injected into the column) was used in order to extend the utility of the model. Mass transfer parameters were calculated using empiric correlations, where the axial dispersion was negligible (Pe > 300) and the mass transfer was controlled by the intraparticle diffusion (Bi > 10). The model assumes a modulator-eluite relationship were the equilibrium constant of the Langmuir isotherm was a function of salt concentration. Adsorption kinetic parameters were estimated from experimental data. The parameters for pure proteins were determined, and elution curves for changes in flow rate, ionic strength gradient, concentration, and sample size were predicted by the model. Then the kinetic parameters of the mixture were determined under the same operational conditions and some of the parameters had to be modified to take into account effects such as protein-protein interactions, competition, and displacement. Experimental elution curves obtained for changes in operational conditions such as flow rate and ionic strength gradient were simulated by the rate model for the protein mixture with a relative error in retention time of visible peaks <5%. IEC operational conditions and the peak fraction collection can be selected using a cost function of the production process which considers yield, purity, concentration, and process time that are obtained from simulations. Operational conditions that gave the minimum cost were selected. Simulations allows to diminish experimental time and cost.

  16. Biolimus-eluting versus everolimus-eluting stents in coronary artery disease: a pooled analysis from the NEXT (NOBORI biolimus-eluting versus XIENCE/PROMUS everolimus-eluting stent) and COMPARE II (Abluminal biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent) randomised trials.

    PubMed

    Vlachojannis, Georgios J; Puricel, Serban; Natsuaki, Masahiro; Morimoto, Takeshi; Smits, Pieter C; Kimura, Takeshi

    2017-03-20

    This study sought to investigate the safety and efficacy of a biolimus-eluting stent with biodegradable polymer (BP-BES) (Nobori; Terumo Corp.) compared to an everolimus-eluting stent with durable polymer (DP-EES) (XIENCE V or Prime; Abbott Vascular, or PROMUS; Boston Scientific). The all-comers NEXT and COMPARE II clinical trials randomly assigned 5,942 patients to BP-BES (N=3,412) or DP-EES (N=2,530). We conducted a patient level pooled analysis at three-year follow-up with specified study endpoints: definite stent thrombosis (ST), the combined safety endpoint cardiac death or target vessel myocardial infarction (TV-MI), and the efficacy endpoint target lesion revascularisation (TLR). At three-year follow-up, all endpoints, namely definite stent thrombosis (BP-BES 0.8% vs. 0.4%, p=0.20), death or TV-MI (BP-BES 7.8% vs. 6.7%, p=0.07), as well as TLR (BP-BES 6.4% vs. 6.4%, p=0.78) were similar between groups. Interestingly, unadjusted (BP-BES 5.6% vs. 4.5%, p=0.02) and adjusted (HR 1.36; 1.01-1.82, p=0.04) TV-MI rates were higher in the BP-BES group than in the DP-EES group. In this large-scale patient level pooled analysis of the NEXT and COMPARE II randomised trials, the use of BP-BES compared with DP-EES resulted in similar outcomes, but with an observed higher rate of TV-MI in the BP-BES group.

  17. [Drug-eluting stents do they make the difference? ].

    PubMed

    Presbitero, P; Asioli, M

    2002-10-01

    The main limitation to further expansion of PTCI (percutaneous transluminal coronary intervention) is restenosis that occurs in 30% of the patients within 6-months after the procedure. Coronary stenting decreases the percent of restenosis due to arterial remodeling after PTCI but proliferation of smooth muscle cells due to vascular injury still remains. A mechanical approach the only treatment up to now (further balloon expansion, plaque removal with rotablator or directional atherectomy) failed. Because the restenotic process is due to a complex series of biological events which start with platelet aggregation, grow-factors and cytochine release, the use of antiflammatory, antithrombotic and antiproliferative drugs were attempted. Cortisone and heparin showed low benefits in clinical trial. New drugs (rapamycin, taxol, actinomycin D, tacrolimus, estradiol, dexamethazone) with antiproliferative and antiflammatory activities are under evaluation. They act as inhibitors of the cell migration and of the cell cicle progression with different specific molecular mechanisms. The first pilot study performed in 45 patients with sirolimus-eluting stents has shown a sustained suppression (25% in the fast release group and 23% in the slow release group) of neointimal formation at 12 months after procedure with absence of restenosis. The Ravel study, a randomized trial, has enrolled 238 patients treated with sirolimus coated stent vs a control group: the results confirm the previous data with a complete suppression of intimal hyperproliferation and restenosis at six months follow-up. The first 400 patients treated in the Sirius trial a similar study which will randomize 1100 pts show a low, but not a complete inhibition of the restenotic process probably due to a more complexity of the lesions treated in comparison to Ravel trial (9.2% of restenosis). Another very promising drug is taxol (paclitaxel). It is an antiproliferative and antinflammatory molecule tested in a series of

  18. 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.

  19. Recent developments in drug-eluting coronary stents.

    PubMed

    Yildiz, Mustafa; Yildiz, Banu Sahin; Gursoy, Mustafa Ozan; Akin, Ibrahim

    2014-01-01

    The interventional treatment of coronary artery disease was introduced in 1970`s by Andreas Grüntzig. The initial treatment strategy with plain old balloon angioplasty (POBA) was associated with high restenosis rates. The introduction of coronary stents, especially drug-eluting stents (DES) in 2002 has improved the results by lowering the rate of in-stent restenosis from 20-40% in the era of bare-metal stent (BMS) to 6-8%. However, in 2006 with the observation of late stent thrombosis the reputations of DES have decreased. However, improvements in stent design especially antiproliferative agents, polymeric agents as well as stent platforms improved newer generation DES. In controlled trials as well as registries the use of second-generation DES as compared to bare-metal stents (BMS) was associated with better clinical and angiographic results. A further development of these stents with use of biodegradable polymers, polymer-free stents, and biodegradable stents on the basis of poly L-lactide (PLLA) or magnesium resulted in third-generation DES and has been evaluated in preclinical and first clinical trials. However, to date, there is a lack of data comparing these third-generation DES with first- and second-generatrion DES in a large scale.

  20. Towards Hypoxia-responsive Drug-eluting Embolization Beads.

    PubMed

    Ashrafi, Koorosh; Heaysman, Clare L; Phillips, Gary J; Lloyd, Andrew W; Lewis, Andrew L

    2017-05-30

    Drug release from chemoembolization microspheres stimulated by the presence of a chemically reducing environment may provide benefits for targeting drug resistant and metastatic hypoxic tumours. A water-soluble disulfide-based bifunctional cross-linker bis(acryloyl)-(l)-cystine (BALC) was synthesised, characterised and incorporated into a modified poly(vinyl) alcohol (PVA) hydrogel beads at varying concentrations using reverse suspension polymerisation. The beads were characterised to confirm the amount of cross-linker within each formulation and its effects on the bead properties. Elemental and UV/visible spectroscopic analysis confirmed the incorporation of BALC within the beads and sizing studies showed that in the presence of a reducing agent, all bead formulations increased in mean diameter. The BALC beads could be loaded with doxorubicin hydrochloride and amounts in excess of 300mg of drug per mL of hydrated beads could be achieved but required conversion of the carboxylic acid groups of the BALC to their sodium carboxylate salt forms. Elution of doxorubicin from the beads demonstrated a controlled release via ionic exchange. Some formulations exhibited an increase in size and release of drug in the presence of a reducing agent, and therefore demonstrated the ability to respond to an in vitro reducing environment. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  1. 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.

  2. Mathematical analysis of perifusion data: models predicting elution concentration.

    PubMed

    Smith, W R; Wake, G C; McIntosh, J E; McIntosh, R P; Pettigrew, M; Kao, R

    1991-07-01

    System models are constructed and analyzed for combined convective flow and for dispersion in distorting concentrations of a chemical signal as it passes through a packed column. We derive general analytical solutions for these models. The results have applications to analyses such as in biological experiments involving hormonal stimulation of perifused cells, elution chromatography, adsorption columns, and studies of groundwater flow. The models reveal that the column distorts an incoming signal (such as a change in solute concentration in the flowing liquid) at the inlet. This distortion is greatest at low values of the Peclet number of the flow and is small at larger values. We explore the effects of the approximations inherent in the mathematical models of the system. Specification of the boundary conditions of the problem are shown to be particularly important. With the use of incorrect models, it is possible to obtain accurate interpolations to data obtained from perfusion experiments. However, the parameters derived (in particular the dispersion constant and the peak concentration of a solute concentration pulse) may be considerably in error. This may lead to errors when these parameter estimates are used to predict results in other experimental situations.

  3. Multi-objective global optimization (MOGO): Algorithm and case study in gradient elution chromatography.

    PubMed

    Freier, Lars; von Lieres, Eric

    2017-07-01

    Biotechnological separation processes are routinely designed and optimized using parallel high-throughput experiments and/or serial experiments. Well-characterized processes can further be optimized using mechanistic models. In all these cases - serial/parallel experiments and modeling - iterative strategies are customarily applied for planning novel experiments/simulations based on the previously acquired knowledge. Process optimization is typically complicated by conflicting design targets, such as productivity and yield. We address these issues by introducing a novel algorithm that combines recently developed approaches for utilizing statistical regression models in multi-objective optimization. The proposed algorithm is demonstrated by simultaneous optimization of elution gradient and pooling strategy for chromatographic separation of a three-component system with respect to purity, yield, and processing time. Gaussian Process Regression Models (GPM) are used for estimating functional relationships between design variables (gradient, pooling) and performance indicators (purity, yield, time). The Pareto front is iteratively approximated by planning new experiments such as to maximize the Expected Hypervolume Improvement (EHVI) as determined from the GPM by Markov Chain Monte Carlo (MCMC) sampling. A comprehensive Monte-Carlo study with in-silico data illustrates efficiency, effectiveness and robustness of the presented Multi-Objective Global Optimization (MOGO) algorithm in determining best compromises between conflicting objectives with comparably very low experimental effort. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Total protein quantitation using the bicinchoninic acid assay and gradient elution moving boundary electrophoresis.

    PubMed

    Kralj, Jason G; Munson, Matthew S; Ross, David

    2014-07-01

    We investigated the ability of gradient elution moving boundary electrophoresis (GEMBE) with capacitively coupled contactless conductivity detection (C(4) D) to assay total protein concentration using the bicinchoninic acid (BCA) reaction. We chose this format because GEMBE-C(4) D behaves as a concentration dependent detection system, unlike optical methods that also rely on pathlength (due to Beer's law). This system tolerates proteins well compared with other capillary electrophoretic methods, allowing the capillary to be reused without coatings or additional hydroxide wash steps. The typical reaction protocol was modified by reducing the pH slightly from 11.25 to 9.4, which enabled elimination of tartrate from the reagents. We estimated that copper (I) could be detected at approximately 3.0 μmol/L, which agrees with similar GEMBE and CZE systems utilizing C(4) D. Under conditions similar to the BCA "micro method" assay, we determined the LOD for three common proteins (insulin, BSA, and bovine gamma globulin) and found that they agree well with the existing spectroscopic detection methods. Further, we investigated how long reaction times impact the LOD and found that the conversion was proportional to log(time). This indicated that little sensitivity is gained by extending the reaction past 1 h. Hence, GEMBE provides an alternative platform for total protein assays while maintaining the excellent sensitivity of the optical-based methods.

  5. 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

    2012-11-07

    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.

  6. In vitro elution characteristics of antibiotic laden BoneSource™, hydroxyapatite bone cement.

    PubMed

    Hernandez-Soria, Alexia; Yang, Xu; Grosso, Matthew J; Reinhart, Janine; Ricciardi, Benjamin F; Bostrom, Mathias

    2013-01-01

    A calcium phosphate - hydroxyapatite (HA) bone cement was loaded with varying concentrations of tobramycin and vancomycin and the elution properties of these antibiotics were evaluated. Nine groups of antibiotic loaded cement cylinders (N = 6 in each group) were prepared and placed in saline for 28 days. Elution rates of tobramycin and vancomycin from the HA cement were evaluated at high, medium, and low doses of incorporated antibiotic. Tobramycin elution rates did not vary according to dose (0.36, 0.18, and 0.09g). Vancomycin elution rates were also not significantly affected by dose (0.1 , 0.05 , and 0.025 g). The combination of tobramycin and vancomycin increased the elution rate of vancomycin for the medium and low dose of tobramycin. The dose of tobramycin did not affect its elution rate from the cement in the combined groups. Importantly, the concentration of antibiotic eluent stayed above the minimum inhibitory concentration for the entire 28 days for all groups except the medium and low dose of vancomycin alone. Overall, elution rates of both tobramycin and vancomycin in the calcium phosphate-HA cement were comparable to those from polymethylmethacryltate beads in vitro.

  7. Blood compatibility of a ferulic acid (FA)-eluting PHBHHx system for biodegradable magnesium stent application.

    PubMed

    Zhang, Erlin; Shen, Feng

    2015-01-01

    Magnesium stent has shown potential application as a new biodegradable stent. However, the fast degradation of magnesium stent limited its clinic application. Recently, a biodegradable and drug-eluting coating system was designed to prevent magnesium from fast degradation by adding ferulic acid (FA) in poly (3-hydroxybutyrate-co-3-hydroxyhexanoate) (PHBHHx) by a physical method. In vitro study has demonstrated that the FA-eluting system exhibited strong promotion to the endothelialization, which might be a choice for the stent application. In this paper, the hemolysis rate, the plasma recalcification time (PRT), the plasma prothrombin time (PT) and the kinetic clotting time of the FA-eluting films were investigated and the platelet adhesion was observed in order to assess the blood compatibility of the FA-eluting PHBHHx films in comparison with PHBHHx film. The results have shown that the addition of FA had no influence on the hemolysis, but prolonged PRT, PT and the clotting time and reduced the platelet adhesion and activation, displaying that the FA-eluting PHBHHx exhibited better blood compatibility than PHBHHx. In addition, the effect of alkali treatment on the blood compatibility of FA-eluting PHBHHx was also studied. It was indicated that alkali treatment had no effect on the hemolysis and the coagulation time, but enhanced slightly the platelet adhesion. All these demonstrated that FA-eluting PHBHHx film had good blood compatibility and might be a candidate surface coating for the biodegradable magnesium stent.

  8. An optimized method for elution of enteroviral RNA from a cellulose-based substrate.

    PubMed

    Li, Yan; Yoshida, Hiromu; Wang, Lu; Tao, Zexin; Wang, Haiyan; Lin, Xiaojuan; Xu, Aiqiang

    2012-12-01

    The Flinders Technology Australia (FTA) Elute Card is a commercial product that facilitates the collection, transport, archiving and processing of nucleic acids from a wide variety of biological samples at room temperature. While the cards have been designed so that sterile/deionized water can elute DNA easily, they are not suitable for some less stable RNAs. This study was undertaken to determine the optimal conditions such as the buffer type, buffer pH and incubation temperature for the elution of enteroviral RNA from FTA Elute Cards prior to quantitative analysis using real-time PCR (qPCR) or consensus degenerate hybrid oligonucleotide primer VP1 RT-semi nested PCR (CODEHOP VP1 RT-snPCR). TE-1 (pH 8.0), rather than sterile water, was the best buffer for high efficiency elution of enteroviral RNA at 95°C. However, as the estimated recovery rate of viral RNA eluted from the cards averaged to be only 6.1%, enterovirus assays using FTA elution should be considered qualitative, especially at low virus titers, and therefore the results of the assay should be interpreted carefully. Copyright © 2012 Elsevier B.V. All rights reserved.

  9. Drug-eluting versus bare-metal coronary stents: where are we now?

    PubMed

    Amoroso, Nicholas S; Bangalore, Sripal

    2012-11-01

    Drug-eluting stents have dramatically reduced the risk of restenosis, but concerns of an increased risk of stent thrombosis have provided uncertainty about their use. Recent studies have continued to show improved procedural and clinical outcomes with drug-eluting stents both in the setting of acute coronary syndromes and stable coronary artery disease. Newer generation drug-eluting stents (especially everolimus-eluting stents) have been shown to be not only efficacious but also safe with reduced risk of stent thrombosis when compared with bare-metal stents, potentially changing the benchmark for stent safety from bare-metal stents to everolimus-eluting stents. While much progress is being made in the development of bioabsorbable polymer stents, nonpolymer stents and bioabsorbable stent technology, it remains to be seen whether these stents will have superior safety and efficacy outcomes compared with the already much improved rates of revascularization and stent thrombosis seen with newer generation stents (everolimus-eluting stents and resolute zotarolimus-eluting stents).

  10. Gradient elution in counter-current chromatography: a new layout for an old path.

    PubMed

    Ignatova, Svetlana; Sumner, Neil; Colclough, Nicola; Sutherland, Ian

    2011-09-09

    Gradient elution in CCC is a powerful tool, which needs further systematic development to become robust and easy to use. The first attempt to build a correlation between gradient elution profile and distribution ratio (K(D)) values for model mixtures containing typical representatives of pharmaceutical compounds is presented in this paper. The three step estimation of the solvent system composition of a heptane-ethyl acetate-methanol-water (HEMWat) series is described. The estimation is based on simple measurements of initial and final stationary phase retention for gradient elution run, calculating gradient distribution ratio and correlating it with static K(D) against HEMWat number.

  11. 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

  12. Drug-eluting stents and acute myocardial infarction: A lethal combination or friends?

    PubMed Central

    Otsuki, Shuji; Sabaté, Manel

    2014-01-01

    Primary percutaneous coronary intervention is the preferred reperfusion strategy for patients presenting with ST-segment elevation myocardial infarction (STEMI). First generation drug-eluting stents (DES), (sirolimus drug-eluting stents and paclitaxel drug-eluting stents), reduce the risk of restenosis and target vessel revascularization compared to bare metal stents. However, stent thrombosis emerged as a major safety concern with first generation DES. In response to these safety issues, second generation DES were developed with different drugs, improved stent platforms and more biocompatible durable or bioabsorbable polymeric coating. This article presents an overview of safety and efficacy of the first and second generation DES in STEMI. PMID:25276295

  13. Intraoperative drug-eluting stent thrombosis in a patient undergoing robotic prostatectomy.

    PubMed

    Sharma, Aarti; Berkeley, Abiona

    2009-11-01

    Insertion of drug-eluting stents is one of the strategies for treating patients with coronary artery disease. These patients can be a perioperative challenge in management as they need to be maintained on antiplatelet therapy to prevent stent thrombosis, which puts them at an increased risk for surgical bleeding. Recently revised guidelines on elective surgery following insertion of a drug-eluting stent recommend dual antiplatelet therapy for a period of twelve months. The management of a patient who presented for surgery more than two years after the insertion of a drug-eluting stent, and who developed in-stent thrombosis intraoperatively, is presented.

  14. A new polymer-free drug-eluting stent with nanocarriers eluting sirolimus from stent-plus-balloon compared with bare-metal stent and with biolimus A9 eluting stent in porcine coronary arteries

    PubMed Central

    Galon, Micheli Z.; Gutierrez, Paulo S.; Sojitra, Prakash; Vyas, Ashwin; Doshi, Manish; Lemos, Pedro A.

    2015-01-01

    Background Permanent polymers in first generation drug-eluting stent (DES) have been imputed to be a possible cause of persistent inflammation, remodeling, malapposition and late stent thrombosis. We aim to describe the in vivo experimental result of a new polymer-free DES eluting sirolimus from stent-plus-balloon (Focus np stent, Envision Scientific) compared with a bare-metal stent (BMS) (Amazonia CroCo, Minvasys) and with a biolimus A9 eluting stent (Biomatrix, Biosensors). Methods In 10 juvenile pigs, 23 coronary stents were implanted in the coronary arteries (8 Amazonia CroCo, 8 Focus np, and 7 Biomatrix). At 28-day follow-up, optical coherence tomography (OCT) and histology were used to evaluate neointimal hyperplasia and healing response. Results According to OCT analysis, Focus np stents had a greater lumen area and less neointimal hyperplasia response than BMS and Biomatrix had. Histomorphometry results showed less neointimal hyperplasia in Focus np than in BMS. Histology showed a higher fibrin deposition in Biomatrix stent compared to Focus np and BMS. Conclusions The new polymer-free DES with sirolimus eluted from stent-plus-balloon demonstrated safety and reduced neointimal proliferation compared with the BMS and Biomatrix stents at 28-day follow-up in this porcine coronary model. This new polymer-free DES is promising and warrants further clinical studies. PMID:25984451

  15. Injectable Drug Eluting Elastomeric Polymer: A Novel Submucosal Injection Material

    PubMed Central

    Tran, Richard T.; Palmer, Michael; Tang, Shou-Jiang; Abell, Thomas L.; Yang, Jian

    2011-01-01

    Background Biodegradable hydrogels can deliver therapeutic payloads with great potentials in endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) to yield improvements in efficacy and foster mucosal regeneration. Objective To assess the efficacy of an injectable drug eluting elastomeric polymer (iDEEP) as a submucosal injection material. Design Comparative study among 3 different solutions using material characterization tests, ex vivo and in vivo porcine models. Setting Academic hospital. Interventions 30 gastric submucosal cushions were achieved with saline (0.9%), sodium hyaluronate (0.4%), and iDEEP (n = 10) in ex vivo porcine stomachs. Four porcine gastric submucosal cushions were then performed in vivo using iDEEP. Main outcome measurements Maximum injection pressure, Rebamipide release rate, submucosal elevation duration, and assessment of in vivo efficacy by en bloc resection. Results No significant difference in injection pressures between iDEEP (28.9 ± 0.3 PSI) and sodium hyaluronate (29.5 ± 0.4 PSI, P > .05) was observed. iDEEP gels displayed a controlled release of Rebamipide up to 2 weeks in vitro. The elevation height of iDEEP (5.7 ± 0.5 mm) was higher than saline (2.8 ± 0.2 mm, P < .01) and SH (4.2 ± 0.2 mm, P < .05). All EMR procedures were successfully performed after injection of iDEEP, and a large gel cushion was noted after the resection procedure. Limitations Benchtop, ex vivo, and non-survival pig study. Conclusions A novel injection solution was evaluated for endoscopic resection. These results suggest that iDEEP may provide a significant step towards the realization of an ideal EMR and ESD injection material. PMID:22301346

  16. Drug-eluting stents and the future of coronary artery bypass surgery: facts and fiction.

    PubMed

    Raja, Shahzad G

    2006-03-01

    The treatment of patients with coronary artery disease continues to evolve. Recent, exciting data on the use of drug-eluting stents in diseased coronary vessels has generated immense enthusiasm within the interventional community leading to claims that "drug-eluting stents will put bypass surgeons out of business." However, despite promising short-term and midterm outcomes of this revolutionary new technology, valid concerns regarding long-term safety and efficacy of drug-eluting stents persist. This review article evaluates current status of drug-eluting stents with special emphasis on real and potential drawbacks of this emerging percutaneous coronary interventional modality and its impact on the practice of coronary artery bypass surgery.

  17. Shotgun electroelution: a proteomic tool for simultaneous sample elution from whole SDS-polyacrylamide gel slabs.

    PubMed

    Antal, József; Bányász, Borbála; Buzás, Zsuzsanna

    2007-02-01

    A high-throughput device has been constructed which allows parallel electroelution of separated SDS-protein bands directly from intact unsectioned polyacrylamide gel slabs as well as single electroelution of certain protein spots into a 384-well standard flat-bottom multiwell plate. The prototype provides complete, quick elution for proteomics from 1-D or from 2-D gels without gel sectioning. Since the elution chamber matrix requires no assembly, sample handling can be easily carried out by existing robotic workstations. The current design is a good candidate for automation of spot elution since there are no moving liquid containing components in the apparatus. Eight SDS-proteins were eluted in test runs and an average 70% sample recovery was achieved by re-electrophoresis of the electro-eluates.

  18. Drug-eluting stents in superficial femoral artery treatment: could they be the standard of care?

    PubMed

    Bosiers, Marc; Deloose, Koen; Callaert, Joren; Peeters, Patrick; Bosiers, Michel

    2016-12-01

    Endovascular techniques have improved markedly over the past several decades. Plain old balloon angioplasty can only reach patencies around 40% after 1 year. Scaffolding stents have resulted in improved short-term results but encountered limitations for longer-term durability. With the introduction of drug-eluting technologies the process of intimal hyperplasia might be slowed, resulting in improved long-term patency results. At first, limus-eluting technologies were not able to transfer the enthusiasm from the coronaries to the infrainguinal vascular bed. However, the newer generation paclitaxel-eluting technologies perform significantly better in femoropopliteal arteries than their non-eluting or non-coated counterparts. The results of a prospective randomized trial comparing DES versus DCB is eagerly awaited. For the moment there seems, based on the meta-analysis, no difference between the two treatment modalities. Although, we need to keep in mind that DCB perform worse in long calcified lesions.

  19. Bicarbonate Elution of Uranium from Amidoxime-Based Polymer Adsorbents for Sequestering Uranium from Seawater

    DOE PAGES

    Pan, Horng-Bin; Wai, Chien M.; Kuo, Li-Jung; ...

    2017-05-02

    Uranium adsorbed on amidoxime-based polyethylene fibers in simulated seawater can be quantitatively eluted using 3 M KHCO3 at 40°C. Thermodynamic calculations are in agreement with the experimental observation that at high bicarbonate concentrations (3 M) uranyl ions bound to amidoxime molecules are converted to uranyl tris-carbonato complex in the aqueous solution. The elution process is basically the reverse reaction of the uranium adsorption process which occurs at a very low bicarbonate concentration (~10-3 M) in seawater. The bicarbonate elution is followed by a NaOH treatment to remove natural organic matter adsorbed on the polymer adsorbent, in real seawater experiments. Furthermore,more » by using the sequential bicarbonate and NaOH elution, the adsorbent is reusable after rinsing with deionized water and the recycled adsorbent shows no loss of uranium loading capacity based on real seawater experiments.« less

  20. Strict vs lenient criteria for elution testing: comparison of yields between two tertiary care medical centers.

    PubMed

    Veeraputhiran, Muthu K; Pesek, Gina A; Blackall, Douglas P

    2011-09-01

    In this study, 2 patient populations, using different elution strategies, were compared to evaluate eluate yields under more and less restrictive conditions. An informative eluate was defined as one in which an antibody that could be clinically significant was detected in the eluate but was not detectable in the plasma at the time of elution testing. The results for 160 direct antiglobulin tests (DATs) and 160 elution studies were evaluated in 71 patients at the adult hospital (lenient criteria). The results for 372 DATs and 43 elution studies were evaluated in 123 patients at the pediatric hospital (strict criteria). The yields from these eluates were 0.6% at the adult hospital (C antibody) vs 2.3% at the pediatric hospital (Jk(a) antibody). Thus, the yield of information from eluate testing is low regardless of the stringency applied to testing. However, considering the cost and time required for testing, more stringent criteria are advised.

  1. Effect of Nanoparticle Surface on the HPLC Elution Profile of Liposomal Nanoparticles.

    PubMed

    Itoh, Naoki; Yamamoto, Eiichi; Santa, Tomofumi; Funatsu, Takashi; Kato, Masaru

    2016-06-01

    Nanoparticles have been used in diverse areas, and even broader applications are expected in the future. Since surface modification can influence the configuration and toxicity of nanoparticles, a rapid screening method is important to ensure nanoparticle quality. We examined the effect of the nanoparticle surface morphology on the HPLC elution profile using two types of 100-nm liposomal nanoparticles (AmBisome(Ⓡ) and DOXIL(Ⓡ)). These 100-nm-sized nanoparticles eluted before the holdup time (about 4 min), even when a column packed with particles with a relatively large pore size (30 nm) was used. The elution time of the nanoparticles increased with pegylation of the nanoparticles and protein adsorption to the nanoparticles; however, the nanoparticles still eluted before the holdup time. The results of this study indicate that HPLC is a suitable tool for rapid evaluation of the surface of liposomal nanoparticles.

  2. 40 CFR 799.6784 - TSCA water solubility: Column elution method; shake flask method.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Development (OECD) Laboratory Intercomparison Testing, Part I, 1979, appeared to be dependent on the chemicals..., Guidelines for The Testing of Chemicals, OECD 105, Water Solubility (Column Elution Method—Shake Flask Method), OECD, Paris, France (1981). ...

  3. 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

  4. Late stent thrombosis after implantation of a sirolimus-eluting stent.

    PubMed

    Kerner, Arthur; Gruberg, Luis; Kapeliovich, Michael; Grenadier, Ehud

    2003-12-01

    Late stent thrombosis in the era of routine high-pressure stent deployment and combined antiplatelet therapy with thienopyridines and aspirin has become a rare but feared complication. We describe a patient with acute myocardial infarction due to late stent thrombosis 6 weeks after deployment of a sirolimus-eluting stent and 2 weeks after the discontinuation of clopidogrel. This is the first report of late thrombosis of a sirolimus-eluting stent.

  5. Proteome Analyses Using Accurate Mass and Elution Time Peptide Tags with Capillary LC Time-of-Flight Mass Spectrometry

    SciTech Connect

    Strittmatter, Eric F.; Ferguson, Patrick L.; Tang, Keqi; Smith, Richard D.

    2003-09-01

    We describe the application of capillary liquid chromatography (LC) time-of-flight (TOF) mass spectrometric instrumentation for the rapid characterization of microbial proteomes. Previously (Lipton et al. Proc. Natl Acad. Sci. USA, 99, 2002, 11049) the peptides from a series of growth conditions of Deinococcus radiodurans have been characterized using capillary LC MS/MS and accurate mass measurements which are logged in an accurate mass and time (AMT) tag database. Using this AMT tag database, detected peptides can be assigned using measurements obtained on a TOF due to the additional use of elution time data as a constraint. When peptide matches are obtained using AMT tags (i.e. using both constraints) unique matches of a mass spectral peak occurs 88% of the time. Not only are AMT tag matches unique in most cases, the coverage of the proteome is high; {approx}3500 unique peptide AMT tags are found on average per capillary LC run. From the results of the AMT tag database search, {approx}900 ORFs detected using LC-TOFMS, with {approx}500 ORFs covered by at least two AMT tags. These results indicate that AMT databases searches with modest mass and elution time criteria can provide proteomic information for approximately one thousand proteins in a single run of <3 hours. The advantage of this method over using MS/MS based techniques is the large number of identifications that occur in a single experiment as well as the basis for improved quantitation. For MS/MS experiments, the number of peptide identifications is severely restricted because of the time required to dissociate the peptides individually. These results demonstrate the utility of the AMT tag approach using capillary LC-TOF MS instruments, and also show that AMT tags developed using other instrumentation can be effectively utilized.

  6. Size and composition of synthetic calcium sulfate beads influence dissolution and elution rates in vitro.

    PubMed

    Roberts, Randy; McConoughey, Stephen J; Calhoun, Jason H

    2014-05-01

    Treatments of osteomyelitis lag behind bacterial resistance to antibiotics. We tested different-sized calcium sulfate beads and their ability to elute multiple antibiotics in vitro as a possible method to improve the therapeutic delivery in patients. Two sizes of calcium sulfate beads (4.8 and 3.0 mm diameter) that contained vancomycin, tobramycin, or both were dissolved in phosphate-buffered saline, and the rate of dissolution by weight and antibiotic elution by the disc diffusion assay and high-pressure liquid chromatography were measured. The 4.8 mm beads showed significantly higher dissolution rates relative to the 3.0 mm beads (2.3 mg/day vs. 1.3 mg/day). While the vancomycin-loaded 4.8 mm beads eluted for a longer time relative to the 3.0 mm beads (20 days vs. 10 days), the smaller beads had threefold higher elution for the first 2 days, before dropping to near zero elution by day 4. The presence of tobramycin extended the elution of the vancomycin to day 40, which closely matches the recommended 6 weeks to treat orthopedic staphylococcus infections. These data suggest that size and content of the bead are variables that could affect their clinical success, and both could be exploited to tailor treatments of specific infections and injuries.

  7. The alkaline elution technique for measuring DNA single strand breaks: increased reliability and sensitivity.

    PubMed

    Koch, C J; Giandomenico, A R

    1994-07-01

    The alkaline elution procedure is noted, on the one hand, for its sensitivity in the detection of DNA damage, but on the other hand, for its extreme variability and inconsistency. These deficiencies in the technique have been traced to incomplete exchanges of the various solutions used in the cell rinse and lysis and DNA rinse and elution portions of the procedure. Solutions to the above indicated problems involve several changes to the standard procedure, including, at the cellular stage, the complete removal of rinsing solutions followed by the addition of lysis solution at 0 degrees C. After standard cell lysis and alkaline rinse of the DNA, the alkaline rinse solution is replaced by elution solution at high flow rate to allow a uniform starting time for the elution, which then proceeds as a nearly first-order function of time (not elution volume). Using gamma-rays as the damaging agent, reproducibility within and between experiments is easily comparable to radiation survival itself, and typically, duplicate elution channels within an experiment provide nearly identical information without the need for internal standards and complex ratiometric analysis techniques. The procedures described allow the reproducible assessment of radiation damage to cellular DNA at doses much below 1 Gy and allow the study of repair processes down to similar levels of residual damage. This unexpected increase in technique sensitivity may be caused by maintenance of near-freezing temperatures during cell manipulation and addition of lysis solutions or to more complete and uniform lysis.

  8. Improved blood compatibility of rapamycin-eluting stent by incorporating curcumin.

    PubMed

    Pan, C J; Tang, J J; Shao, Z Y; Wang, J; Huang, N

    2007-09-01

    This paper dealt with improving the blood compatibility of the rapamycin-eluting stent by incorporating curcumin. The rapamycin- and rapamycin/curcumin-loaded PLGA (poly(d,l-lactic acid-co-glycolic acid)) coatings were fabricated onto the surface of the stainless steel stents using an ultrasonic atomization spray method. The structure of the coating films was characterized by Fourier transform infrared spectroscopy (FTIR). The optical microscopy and scanning electron microscopy (SEM) images of the drug-eluting stents indicated that the surface of all drug-eluting stents was very smooth and uniform, and there were not webbings and "bridges" between struts. There were not any cracks and delaminations on stent surface after expanded by the angioplasty balloon. The in vitro platelet adhesion and activation were investigated by static platelet adhesion test and GMP140 (P-selection), respectively. The clotting time was examined by activated partially prothromplastin time (APTT) test. The fibrinogen adsorption on the drug-loaded PLGA films was evaluated by enzyme-linked immunosorbent assay (ELISA). All obtained data showed that incorporating curcumin in rapamycin-loaded PLGA coating can significantly decrease platelet adhesion and activation, prolong APTT clotting time as well as decrease the fibrinogen adsorption. All results indicated that incorporating curcumin in rapamycin-eluting coating obviously improve the blood compatibility of rapamycin-eluting stents. It was suggested that it may be possible to develop a drug-eluting stent which had the characteristics of not only good anti-proliferation but also improved anticoagulation.

  9. Elution parameters in constant-pressure, single-ramp temperature-programmed gas chromatography.

    PubMed

    Blumberg, L M; Klee, M S

    2001-05-18

    The dependence of the degree of interaction of a solute with the stationary phase at the time of its elution from the column in temperature-programmed GC is best described by interaction level of the solute. The latter represents the fraction of a solute residing in the stationary phase relative to the total amount of the solute. A simple approach to the evaluation of interaction levels of eluting solutes in a single-ramp temperature program is proposed. In a single-ramp temperature program having no preceding temperature plateau, all solutes that elute at temperatures that are about 60 degrees C higher than the initial temperature of the heating ramp elute with nearly the same interaction levels that can be found as exp(-r), where r is dimensionless heating rate. A specially designed temperature plateau preceding the ramp causes all solutes eluting during the entire time of the ramp to elute with nearly the same interaction levels equal to exp(-r). A transformation of the interaction level of a solute into its retention factor or mobility factor (a fraction of a solute in a mobile phase in relation to the total amount of the solute) and vice versa is also described.

  10. Elution of lead from lead zirconate titanate ceramics to acid rain

    NASA Astrophysics Data System (ADS)

    Tsurumi, Takaaki; Takezawa, Shuhei; Hoshina, Takuya; Takeda, Hiroaki

    2017-10-01

    The amount of lead that eluted from lead zirconate titanate (PZT) ceramics to artificial acid rain was evaluated. Four kinds of PZT ceramics, namely, pure PZT at MPB composition, CuO-added PZT, PZT with 10 mol % substitution of Ba for Pb, and CuO-added PZT with 10 mol % substitution of Ba for Pb, were used as samples of the elution test. These PZT ceramics of 8 mm2 and 1.1–1.2 mm thickness were suspended in 300 ml of H2SO4 solution of pH 4.0. The concentration of lead eluted from PZT was in the range from 0.2 to 0.8 ppm. It was found that both liquid phase formation by the addition of CuO and the substitution of Ba for Pb were effective to reduce the amount of lead that eluted. By fitting the leaching out curve with a classical equation, a master curve assuming no sampling effect was obtained. The lead concentration evaluated from the amount of lead that eluted from a commercial PZT plate to H2SO4 solution of pH 5.3 was almost the same as the limit in city water. It is concluded that PZT is not harmful to health and the environment and the amount of lead that eluted from PZT can be controlled by modifying PZT composition.

  11. Measurement of DNA single-strand breaks by alkaline elution and fluorometric DNA quantification.

    PubMed

    Goumenou, Marina; Machera, Kyriaki

    2004-03-15

    The method presented is based on the alkaline elution procedure for the determination of DNA single-stand (ss) breaks developed by Kohn and on the principles of DNA quantification after binding with the dye Hoechst 33258. In the present study, modification of the alkaline elution procedure with regard to the elution solution volume was performed. The influences of the DNA strandedness, the ethylenediaminetetraacetate/tetraethylammonium hydroxide denaturation and elution solution presence, the DNA solution pH, the dye amount, and the incubation time for the formation of the dye-ssDNA complex on the DNA fluorometric quantification were also studied. The modified DNA alkaline elution procedure followed by the optimized fluorometric determination of the ssDNA was applied on liver tissue from both untreated and treated (N-nitroso-N-methylurea- administered) Wistar rats. The criteria for the selection of the appropriate estimator and statistical analysis of the obtained results are also presented. The method of the DNA alkaline elution followed by fluorometric determination of ssDNA as modified and evaluated is an accurate and reliable approach for the determination of in vivo induced ssDNA strand breaks.

  12. Modeling of salt and pH gradient elution in ion-exchange chromatography.

    PubMed

    Schmidt, Michael; Hafner, Mathias; Frech, Christian

    2014-01-01

    The separation of proteins by internally and externally generated pH gradients in chromatofocusing on ion-exchange columns is a well-established analytical method with a large number of applications. In this work, a stoichiometric displacement model was used to describe the retention behavior of lysozyme on SP Sepharose FF and a monoclonal antibody on Fractogel SO3 (S) in linear salt and pH gradient elution. The pH dependence of the binding charge B in the linear gradient elution model is introduced using a protein net charge model, while the pH dependence of the equilibrium constant is based on a thermodynamic approach. The model parameter and pH dependences are calculated from linear salt gradient elutions at different pH values as well as from linear pH gradient elutions at different fixed salt concentrations. The application of the model for the well-characterized protein lysozyme resulted in almost identical model parameters based on either linear salt or pH gradient elution data. For the antibody, only the approach based on linear pH gradients is feasible because of the limited pH range useful for salt gradient elution. The application of the model for the separation of an acid variant of the antibody from the major monomeric form is discussed.

  13. Development of a safe dexamethasone-eluting electrode array for cochlear implantation.

    PubMed

    Stathopoulos, Dimitra; Chambers, Scott; Enke, Ya Lang; Timbol, Godofredo; Risi, Frank; Miller, Christopher; Cowan, Robert; Newbold, Carrie

    2014-09-01

    Cochlear implantation can result in trauma leading to increased tissue response and loss of residual hearing. A single intratympanic application of the corticosteroid dexamethasone is sometimes used clinically during surgery to combat the potential effect of trauma on residual hearing. This project looked at the safety and efficacy of dexamethasone eluted from an intracochlear array in vivo. Three trials were conducted using normal hearing adult guinea pigs implanted with successive iterations of dexamethasone-eluting (DX1, DX2, and DX3) or non-eluting (control) intracochlear electrode arrays. The experimental period for each animal was 90 days during which hearing tests were performed at multiple time points. There was no significant difference between matched control array and dexamethasone array groups in terms of spiral ganglion neuron density, organ of Corti condition, or fibrosis and ossification. A cochleostomy seal was present in all implanted cochleae. There were no differences in the degree of hearing threshold shifts between DX1 and DX3 and their respective control arrays. Cochleae implanted with DX2 arrays showed less hearing loss and marginally better spiral ganglion neuron survival than their control array counterparts. Post-explant inspection of the DX2 and DX3 arrays revealed a difference in pore density following dexamethasone elution. The dexamethasone doses used were safe in the guinea pig cochlea. Dexamethasone did not inhibit formation of a cochleostomy seal. The level of hearing protection afforded by dexamethasone eluting from an intracochlear array may depend upon the degree of elution and level of trauma inflicted.

  14. 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.

  15. Chromatofocusing profile of purified human alpha-fetoprotein and albumin differs from those of crude samples: effect of protein concentration of the elution of the sample.

    PubMed

    Leal, J A; Eddy, K B; Keel, B A

    1991-02-01

    Chromatofocusing was utilized to characterize charge microheterogeneity of purified human alpha-fetoprotein (AFP) and human serum albumin (HSA). Crude cord blood samples yielded three isoforms: AFP-IA, IB, and II, with pIs 4.57 (52%), 4.27 (43%), and less than 4.00 (5%), respectively. In contrast, 10 micrograms of purified AFP or 250,000 cpm of 125I-AFP eluted entirely as isoform AFP-II. 125I-AFP focused in the presence of crude cord blood, amniotic fluid, adult male serum, or 25 mg purified HSA resulted in elution profiles similar to those of crude cord blood. Pure AFP focused along with 0.1, 1.0, 5.0, or 10 mg HSA showed a gradual shift from AFP-II to AFP-I. With greater than or equal to 5 mg HSA, isoform I was further resolve into AFP-IA and IB. Similarly, 250,000 cpm of 125I-HSA, which also eluted entirely as isoform II, showed a gradual shift to isoform I when increasing concentrations of unlabeled HSA were added. The resolution of isoform HSA-I in HSA-IA, IB, and IC was again improved with greater than or equal to 5 mg unlabeled HSA. When carrier proteins of varying pI values were chromatofocused along with purified AFP, it was observed that only those proteins with pIs in the range of AFP caused significant alteration in the relative distribution of AFP. We conclude that sample protein concentration and composition must be carefully considered when chromatofocusing is being used for purified samples and when the elution profiles of samples from different origins and varying protein concentrations are being compared.

  16. Comparison of everolimus- and biolimus-eluting coronary stents with everolimus-eluting bioresorbable vascular scaffolds: Two-year clinical outcomes of the EVERBIO II trial.

    PubMed

    Arroyo, Diego; Gendre, Gregoire; Schukraft, Sara; Kallinikou, Zacharenia; Müller, Olivier; Baeriswyl, Gérard; Stauffer, Jean-Christophe; Goy, Jean-Jacques; Togni, Mario; Cook, Stéphane; Puricel, Serban

    2017-09-15

    Data from randomized controlled trials have shown that the ABSORB BVS is non-inferior to Cobalt Chromium everolimus-eluting stents at 2years. The EVERBIO II trial (Comparison of Everolimus- and Biolimus-Eluting Coronary Stents with Everolimus-Eluting Bioresorbable Vascular Scaffold) is a single-center, assessor-blind, randomized controlled trial enrolling 240 patients with an allocation ration of 1:1:1 conducted at University and Hospital Fribourg, Switzerland. The studied devices were an everolimus-eluting persistent polymer stent (EES), a biolimus-eluting stent with bioabsorbable polymer (BES) and a fully bioresorbable vascular scaffold (BVS). Clinical end points collected at 9months, 12months, and 2years, were academic research consortium defined composites, device thrombosis and target-vessel revascularization. Clinical follow-up at 2years was available in 96% (N=77) of patients in the EES group, in 100% (N=80) in the BES and 99% (N=77) in the BVS group. The device-oriented composite end point of cardiac death, target-vessel myocardial infarction and target-lesion revascularization occurred in 13 (16%) patients treated with EES, in 7 (9%) patients treated with BES and in 16 (21%) patients treated with BVS. There was no significant difference when the metallic stents were compared to the BVS (p=0.12). There was one late scaffold thrombosis throughout the trial in the BVS group, and no definite stent thrombosis in either EES or BES treated patients. The current analysis shows no significant differences with regard to clinical outcomes at 2years between BVS and the best-in-class metallic DES. Event rates were numerically higher in BVS-treated patients. However, when BVS were compared to BES alone, the occurrence of device related adverse events was significantly increased. Copyright © 2017. Published by Elsevier B.V.

  17. Comparison of abluminal biodegradable polymer biolimus-eluting stents and durable polymer everolimus-eluting stents in the treatment of coronary bifurcations.

    PubMed

    Costopoulos, Charis; Latib, Azeem; Naganuma, Toru; Sticchi, Alessandro; Ferrarello, Santo; Regazzoli, Damiano; Chieffo, Alaide; Figini, Filippo; Carlino, Mauro; Montorfano, Matteo; Naim, Charbel; Kawaguchi, Masanori; Gerasimou, Argyrios; Giannini, Francesco; Godino, Cosmo; Colombo, Antonio

    2014-05-01

    To compare biodegradable polymer biolimus-eluting (BES) with abluminal drug elution and durable polymer everolimus-eluting (EES) stents in the treatment of bifurcation lesions. The persistence of a polymer in drug-eluting stents (DES) following drug elution has been viewed as a possible culprit for restenosis. DES with biodegradable polymer may thus be associated with improved clinical outcomes, especially in high-risk lesions such as those at bifurcation sites. We performed a retrospective study of consecutive de novo bifurcation lesions treated with EES between October 2006 and October 2011 and BES between February 2008 and March 2012. Study endpoints included major adverse cardiac events (MACE) defined as all-cause death, myocardial infarction (MI), including peri-procedural MI, and target vessel revascularization (TVR) as well as target lesion revascularization (TLR) separately. We analyzed 236 bifurcation lesions treated with either BES (79 lesions in 69 patients) or EES (157 lesions in 154 patients). Patient and procedural characteristics were broadly similar between the two groups. Estimated MACE and TVR rates at 2-year follow-up were similar between the BES and EES groups (MACE = 13.6 ± 4.6% vs. 14.6 ± 3.2% (P = 0.871); TVR = 6.9 ± 3.5% vs. 8.0 ± 2.7% (P = 0.889). No significant differences were noted between the two groups following propensity-score matched analysis. There was no probable or definite stent thrombosis. BES use in the treatment of bifurcation lesions appears to be associated with good clinical outcomes, comparable to those seen with EES, at long-term follow-up. These results are hypothesis-generating and need to be validated with larger studies. Copyright © 2013 Wiley Periodicals, Inc.

  18. Simulation of elution profiles in liquid chromatography-I: Gradient elution conditions, and with mismatched injection and mobile phase solvents.

    PubMed

    Jeong, Lena N; Sajulga, Ray; Forte, Steven G; Stoll, Dwight R; Rutan, Sarah C

    2016-07-29

    High-performance liquid chromatography (HPLC) simulators are effective method development tools. The goal of the present work was to design and implement a simple algorithm for simulation of liquid chromatographic separations that allows for characterization of the effect of injection solvent mismatch and injection solvent volume overload. The simulations yield full analyte profiles during solute migration and at elution, which enable a thorough physical understanding of the effects of method variables on chromatographic performance. The Craig counter-current distribution model (the plate model) is used as the basis for simulation, where a local retention factor is assigned for each spatial and temporal element within the simulation. The algorithm, which is an adaptation of an approach originally described by Czok and Guiochon (Ref. [10]), is sufficiently flexible to allow the use of either linear (e.g., Linear Solvent Strength Theory) or non-linear models of solute retention (e.g., Neue-Kuss (Ref. [36])). In this study, both types of models were used, one for simulating separations of a homologous series of alkylbenzenes, and the other for separations of selected amphetamines. The simulation program was validated first by comparison of simulated retention times and peak widths for five amphetamines to predictions obtained using linear solvent strength (LSS) theory, and to results from experimental separations of these compounds. The simulated retention times for the amphetamines agreed within 0.02% and 2.5% compared to theory and experiment, respectively. Secondly, the program was evaluated for simulating the case where there is a compositional mismatch between the mobile phase at the column inlet and the injection solvent (i.e., the sample matrix). This work involved alkylbenzenes, and retention time and peak width predictions from simulations were within 1.5 and 6.0% of experimental values, respectively, even without correction for extra-column dispersion. The

  19. Defining a new standard for IVUS optimized drug eluting stent implantation: the PRAVIO study.

    PubMed

    Gerber, R T; Latib, A; Ielasi, A; Cosgrave, J; Qasim, A; Airoldi, F; Chieffo, A; Montorfano, M; Carlino, M; Michev, I; Tobis, J; Colombo, A

    2009-08-01

    Preliminary Investigation to the Angiographic Versus IVUS Optimization Trial is a single center prospective observational intravascular ultrasound (IVUS) guided stent implantation study assessing new criteria for optimal drug eluting stent (DES) deployment. IVUS assessment of DES often reveals underexpansion and malapposition. Optimal stent deployment is currently poorly defined and previous criteria may not be suitable in long and complex lesions. Optimization was defined as achieving >/or 70% of the cross-sectional area (CSA) of the postdilation balloon. This criterion was applied in 113 complex lesions. The size of this balloon was calculated according to vessel media-to-media diameters at various sites inside the stented segment. The IVUS guided treated lesions were matched according to diabetes, vessel type, reference vessel diameter, minimum lumen diameter (MLD), and lesion length with a group of angiographic treated lesions to compare final MLD achieved. Mean minimum stent CSA according to the postdilation balloon utilized was 4.62 mm(2), 6.26 mm(2), 7.87 mm(2), and 9.87 mm(2) for 2.5 mm, 3.0 mm, 3.5 mm, and 4 mm balloons, respectively. Final MLD (mm) was significantly larger in the IVUS compared to the angiographic-guided group (3.09 +/- 0.50 vs. 2.67 +/- 0.54; P < 0.0001). There were no procedural complications related to IVUS use. We propose new IVUS criteria based on vessel remodeling that results in an increment in the final MLD, compared to angiographic guidance, which is much larger than any previously published study. This criterion seems to be safely achievable. A proposed randomized study (angiographic vs. IVUS optimization trial) has been launched to test these concepts. (c) 2008 Wiley-Liss, Inc.

  20. Disappearing and Reappearing Differences in Drug-Eluting Stent Use by Race

    PubMed Central

    Federspiel, Jerome J; Stearns, Sally C; Reiter, Kristin L; Geissler, Kimberley H; Triplette, Matthew A; D’Arcy, Laura P; Sheridan, Brett C; Rossi, Joseph S

    2011-01-01

    Aim Drug-eluting coronary stents (DES) rapidly dominated the marketplace in the United States after approval by the Food and Drug Administration in April 2003, but utilization rates were initially lower among African-American patients. We assess whether racial differences persisted as DES diffused into practice. Methods Medicare claims data were used to identify coronary stenting procedures among elderly patients with acute coronary syndromes (ACS). Regression models of the choice of DES versus bare mental stent controlled for demographics, ACS type, comorbidities, and hospital characteristics. Diffusion was assessed in the short run (2003–2004) and long run (2007), with the effect of African-American race calculated in each period to allow for a varying effect. Results The sample included 381,887 Medicare beneficiaries treated with stent insertion; approximately five percent were African-American. Initially (May 2003–February 2004), African-American race was associated with lower DES use compared to other races (44.3% vs. 46.5%, p<0.01). Once DES usage was high in all patients (March-December 2004), differences were not significant (79.8% vs. 80.3%, p=0.45). Subsequent concerns regarding DES safety caused broad reductions in DES use, with African-Americans having lower rates of use than other racial groups in 2007 (63.1% versus 65.2%, p<0.01). Conclusions Racial disparities in DES use initially disappeared during a period of rapid diffusion and high usage rates; the reappearance of disparities in use by 2007 may reflect DES use tailored to unmeasured aspects of case mix and socioeconomic status. Further work is needed to whether underlying differences in race reflect physician decisions regarding appropriateness of treatment. PMID:22132712

  1. 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.

  2. 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

  3. 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.

  4. Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model

    PubMed Central

    Wang, Ting; Zhang, Jie; Wang, Juan; Pei, Ying-Hua; Qiu, Xiao-Jian; Wang, Yu-Ling

    2016-01-01

    Background: Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug. Methods: Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent. Results: Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect. Conclusions: The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future. PMID:27824004

  5. Labview utilities

    SciTech Connect

    Persaud, Arun

    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.

  6. Safety and efficacy of different paclitaxel-eluting balloons in a porcine model.

    PubMed

    Pérez de Prado, Armando; Pérez-Martínez, Claudia; Cuellas Ramón, Carlos; Regueiro Purriños, Marta; Diego Nieto, Alejandro; Gonzalo-Orden, José M; Molina Crisol, María; Gómez Castel, Alex; Duocastella Codina, Luis; Fernández-Vázquez, Felipe

    2014-06-01

    Paclitaxel-eluting balloons have shown high antiproliferative efficacy in the treatment and prevention of restenosis. Nevertheless, not all available devices are equally effective, which makes it interesting to compare results in a preclinical model. Our objective was to assess the preclinical efficacy and safety of different devices. We implanted 51 metallic stents (Architect(®), iVascular) in 17 domestic swine (mean, 25 [3] kg), inserting 1 stent per major coronary artery. Stent postdilatation was performed with different control balloons (n=10) or paclitaxel-eluting balloons: paclitaxel-eluting balloon 1 (iVascular) (n=15); paclitaxel-eluting balloon 2 (iVascular) (n=16) and In.Pact Falcon(®) (Medtronic) (n=10). The restenosis rate (using angiography and histomorphometry) and vascular healing parameters (balloon-related vascular injury score, endothelialization rate, and fibrin and inflammation scores) were analyzed at 28 days. The distinct paclitaxel-eluting balloons showed a similar degree of stenosis at follow-up, which was significantly lower than that in the control group: diameter stenosis was 9% (12%) vs 34% (18%) by angiography (P<.0001) and was 22% (8%) vs 51% (18%) by histomorphometry (P<.0001). Scores for vascular injury (mean, 0.6 [0.5]) and inflammation (mean, 0.8 [0.3]) were uniformly low across all groups. Drug effect markers differed significantly between the paclitaxel-eluting balloons and control groups, with lower endothelialization rates (87% [10%] vs 99% [2%]; P=.0007) and higher fibrin scores (2.1 [0.7] vs 0.4 [0.5]; P<.0001) in the paclitaxel-eluting balloons groups. There were no differences between the different paclitaxel-eluting balloons. In this preclinical model, the paclitaxel-eluting balloons studied significantly reduced in-stent restenosis compared with the control balloons. Although there were no findings of persistent vascular injury or inflammation, delayed endothelialization and fibrin aggregate suggest a drug deposition

  7. Clinical Impact of Intravascular Ultrasound-Guided Chronic Total Occlusion Intervention With Zotarolimus-Eluting Versus Biolimus-Eluting Stent Implantation: Randomized Study.

    PubMed

    Kim, Byeong-Keuk; Shin, Dong-Ho; Hong, Myeong-Ki; Park, Hun Sik; Rha, Seung-Woon; Mintz, Gary S; Kim, Jung-Sun; Kim, Je Sang; Lee, Seung-Jin; Kim, Hee-Yeol; Hong, Bum-Kee; Kang, Woong-Chol; Choi, Jin-Ho; Jang, Yangsoo

    2015-07-01

    There have been no randomized studies comparing intravascular ultrasound (IVUS)-guided versus conventional angiography-guided chronic total occlusion (CTO) intervention using new-generation drug-eluting stent Therefore, we conducted a prospective, randomized, multicenter trial designed to test the hypothesis that IVUS-guided CTO intervention is superior to angiography-guided intervention. After successful guidewire crossing, 402 patients with CTOs were randomized to the IVUS-guided group (n=201) or the angiography-guided group (n=201) and secondarily randomized to Resolute zotarolimus-eluting stents or Nobori biolimus-eluting stents. The primary and secondary end points were cardiac death and a major adverse cardiac event defined as the composite of cardiac death, myocardial infarction, or target-vessel revascularization, respectively. After 12-month follow-up, the rate of cardiac death was not significantly different between the IVUS-guided group (0%) and the angiography-guided group (1.0%; P by log-rank test=0.16). However, major adverse cardiac event rates were significantly lower in the IVUS-guided group than that in the angiography-guided group (2.6% versus 7.1%; P=0.035; hazard ratio, 0.35; 95% confidence interval, 0.13-0.97). Occurrence of the composite of cardiac death or myocardial infarction was significantly lower in the IVUS-guided group (0%) than in the angiography-guided group (2.0%; P=0.045). The rates of target-vessel revascularization were not significantly different between the 2 groups. In the comparison between Resolute zotarolimus-eluting stent and Nobori biolimus-eluting stent, major adverse cardiac event rates were not significantly different (4.0% versus 5.7%; P=0.45). Although IVUS-guided CTO intervention did not significantly reduce cardiac mortality, this randomized study demonstrated that IVUS-guided CTO intervention might improve 12-month major adverse cardiac event rate after new-generation drug-eluting stent implantation when compared

  8. Elution profiles of cefazolin from PMMA and calcium sulfate beads prepared from commercial cefazolin formulations.

    PubMed

    Udomkusonsri, Pareeya; Kaewmokul, Santi; Arthitvong, Surapong; Phaochoosak, Napasorn

    2012-03-01

    Antibiotic beads have become popular for the treatment of local bacterial infections. The preparation of antibiotic beads from commercial pharmaceutical antibiotics is a convenient method in clinic. The elution characteristics of cefazolin from polymethylmethacrylate (PMMA) (SmartSet HV, Depuy I and Cemfix 3) beads and calcium sulfate beads were studied. Commercial cefazolin formulation was incorporated in PMMA or calcium sulfate at 1 g cefazolin/10 g of matrix substances to form beads. The concentrations of eluted cefazolin during 15 days were greater than MIC for Staphylococcus aureus (ATCC 25923). The eluted cefazolin concentrations were in the range of 3.6 ± 1.2 to 4.6 ± 0.4 mg for PMMA beads and 15.4 ± 1.7 mg for calcium sulfate beads. The accumulated eluted cefazolin from PMMA beads and calcium sulfate beads for 15 days were 34.41 ± 3.93 to 38.67 ± 3.04% and 95.94 ± 3.93%, respectively. The various storage conditions; at room temperature or 4°C, with or without light-protection, for 6 months had little effects on the amounts of eluted cefazolin. The results showed both in-housed cefazolin-PMMA beads and cefazolin-calcium sulfate beads could be the effective tools for the treatment of local bacterial infections.

  9. Correlation of elution and sensitivity of cell lines to dental composites.

    PubMed

    Susila, Anand V; Balasubramanian, Venkatesh

    2016-03-01

    The aim of the present study was to understand the role played by composition on the elution of dental composites and the subsequent cytotoxicity, the sensitivity of different cell lines to eluates on a temporal basis and the correlation of the two parameters elution and cytotoxicity. LC-MS was done to analyze the eluates. MTT assay was done to assess cytotoxicity on two cell lines. Eluates were found to have matrix monomers, photoinitiators and their degradation products. The short-term viability of other mammalian cell line was inferior to human cell line. However human cell line became more sensitive to long-term incubation with composites. There was a strong inverse correlation to elution of monomers and photoinitiators and cell viability for both cell lines. Bisphenol A elution did not correlate to cell viability. Other mammalian cell lines may be more sensitive to acute toxin build-up than human cell line while the latter may be more sensitive to prolonged toxin exposure. Dimethacrylate based composites elute more and exert strong cytotoxicity than Ormocer and Silorane based composites. Most of the eluates correlated linearly to cytotoxicity. Copyright © 2015 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  10. DNA Adsorption to and Elution from Silica Surfaces: Influence of Amino Acid Buffers

    PubMed Central

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

    2014-01-01

    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. PMID:23931415

  11. 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.

  12. 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.

  13. Establishing conditions for the storage and elution of rabies virus RNA using FTA® cards

    PubMed Central

    SAKAI, Takeo; ISHII, Ayako; SEGAWA, Takao; TAKAGI, Yukihiko; KOBAYASHI, Yuki; ITOU, Takuya

    2014-01-01

    The Flinders Technology Associates filter paper cards (FTA® cards) can be used to store nucleic acid from various samples and are easily portable. However, RNA is physicochemically unstable compared with DNA, and appropriate methods have not been established for storage and extraction of RNA from FTA® cards. The present study investigated the optimum conditions for storage and elution of viral RNA (vRNA) using rabies virus (RABV) applied to FTA® cards. When TE buffer was used, the elution rates of vRNA increased with the length of the elution time. When the cards were stored at −80°C or −20°C, vRNA was stable over 3 months. Degradation of vRNAs occurred following storage at 4°C and room temperature, suggesting that RNA should be extracted from cards as soon as possible if no freezer is available. When we tried to amplify vRNA from RABV-infected animal brains applied to FTA® cards and stored at −80°C for 6 months, we did not detect any amplified products with the primer set for 964 bp of RABV N gene. However, we were able to detect amplified products by increasing the elution time of vRNA from FTA® cards from 30 min to 24 hr or by changing the primer sets to amplify 290 bp of N gene. Thus, we recommend extending the elution time for damaged or low concentration samples in FTA® cards. PMID:25648208

  14. Contrasting Effects of Physical Wear on Elution of Two Antibiotics from Orthopedic Cement

    PubMed Central

    Dodds, S.; Akid, R.; Stephenson, J.; Nichol, T.; Banerjee, R. D.; Stockley, I.; Townsend, R.

    2012-01-01

    The use of antibiotics as a supplement to bone cement for the purposes of providing a local release of antibiotics is common practice in arthroplasty surgery and the kinetics of elution of the antibiotics in such systems have been investigated previously. However, in these previous studies no account was taken of the potential effects that wear may have on the elution kinetics of the antibiotic. Here, we have modified an existing wear testing rig to allow the simultaneous study of the elution kinetics of bone cement samples containing antibiotics being subjected to immersion only and immersion and conjoint wear. The results show contrasting effects with two commonly used antibiotics. Bone cement containing daptomycin showed no substantial change in antibiotic elution due to wear, while cement containing gentamicin (the most commonly used antibiotic in this application) in contrast demonstrated a substantial reduction in the rate of antibiotic elution when wear was applied. Scanning electron microscopy revealed a possible explanation for these diverse results, due to wear-induced “sealing” of the surface in conjunction with the crystal morphology of the antibiotic. PMID:22155831

  15. 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.

  16. Selection of the Optimum Electrospray Voltage for Gradient Elution LC-MS Measurements

    PubMed Central

    Marginean, Ioan; Kelly, Ryan T.; Moore, Ronald J.; Prior, David C.; LaMarche, Brian L.; Tang, Keqi; Smith, Richard D.

    2009-01-01

    Changes in liquid composition during gradient elution liquid chromatography (LC) coupled to mass spectrometry (MS) analyses affect the electrospray operation. To establish methodologies for judicious selection of the electrospray voltage, we monitored in real-time the effect of the LC gradient on the spray current. The optimum range of the electrospray voltage decreased as the concentration of organic solvent in the eluent increased during reversed-phase LC analyses. These results provided the means to rationally select the voltage so as to ensure effective electrospray operation throughout gradient-elution LC separations. For analyses in which the electrospray was operated at constant voltage, a small run-to-run variation in the spray current was observed, indicating a changing electric field due to fouling or degradation of the emitter. Algorithms using feedback from spray current measurements to maintain the electrospray voltage within the optimum operating range throughout gradient elution LC-MS were evaluated. The electrospray operation with voltage regulation and at a constant, judiciously selected voltage during gradient elution LC-MS measurements produced data with similar reproducibility. SYNOPSIS Electrospray current measurements during gradient elution liquid chromatography analyses provide reliable feedback for monitoring, understanding, and improving performance. PMID:19196520

  17. Final 3-Year Outcome of a Randomized Trial Comparing Second-Generation Drug-Eluting Stents Using Either Biodegradable Polymer or Durable Polymer: NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial.

    PubMed

    Natsuaki, Masahiro; Kozuma, Ken; Morimoto, Takeshi; Kadota, Kazushige; Muramatsu, Toshiya; Nakagawa, Yoshihisa; Akasaka, Takashi; Igarashi, Keiichi; Tanabe, Kengo; Morino, Yoshihiro; Ishikawa, Tetsuya; Nishikawa, Hideo; Awata, Masaki; Abe, Mitsuru; Okada, Hisayuki; Takatsu, Yoshiki; Ogata, Nobuhiko; Kimura, Kazuo; Urasawa, Kazushi; Tarutani, Yasuhiro; Shiode, Nobuo; Kimura, Takeshi

    2015-10-01

    There is a paucity of data reporting the clinical outcomes of biodegradable polymer biolimus-eluting stent (BP-BES) compared with durable polymer everolimus-eluting stent (DP-EES) beyond 1 year after stent implantation when the polymer is fully degraded. The NOBORI Biolimus-Eluting Versus XIENCE/PROMUS Everolimus-Eluting Stent Trial (NEXT) is a prospective, multicenter, randomized, open-label, noninferiority trial comparing BP-BES with DP-EES in patients scheduled for percutaneous coronary intervention using drug-eluting stent (DES) without any exclusion criteria among 98 participating centers in Japan. The trial was designed to evaluate noninferiority of BP-BES relative to DP-EES in terms of any target-lesion revascularization at 1 year and death or myocardial infarction at 3 years. Between May and October 2011, 3235 patients were randomly assigned to receive either BP-BES (1617 patients) or DP-EES (1618 patients). Complete 3-year follow-up was achieved in 97.6% of patients. At 3 years, the primary safety end point of death or myocardial infarction occurred in 159 patients (9.9%) in the BP-BES group and in 166 patients (10.3%) in the DP-EES group, demonstrating noninferiority of BP-BES relative to DP-EES (P noninferiority<0.0001 and P superiority=0.7). Cumulative incidence of target-lesion revascularization was not significantly different between the 2 groups (7.4% versus 7.1%; P=0.8). By a landmark analysis at 1 year, the cumulative incidences of death or myocardial infarction and target-lesion revascularization were also not significantly different between the 2 groups (4.6% versus 5.2%; P=0.46 and 3.3% versus 2.7%; P=0.39, respectively). Safety and efficacy outcomes of BP-BES were non inferior to those of DP-EES 3 years after stent implantation. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01303640. © 2015 American Heart Association, Inc.

  18. In vitro tobramycin elution analysis from a novel beta-tricalcium phosphate-silicate-xerogel biodegradable drug-delivery system.

    PubMed

    DiCicco, Michael; Goldfinger, Aaron; Guirand, Felix; Abdullah, Aquill; Jansen, Susan A

    2004-07-15

    This in vitro research analyzed local tobramycin elution characteristics from a novel, biodegradable drug delivery system, consisting of a beta-TCP bone substitute, VITOSS trade mark, encapsulated with silicate xerogel prepared by the sol-gel process. Tobramycin elution from silicate-xerogel-encapsulated VITOSS was compared directly with non-silicate-xerogel-encapsulated VITOSS to assess whether xerogels are effective in delivering greater tobramycin quantities in a controllable, sustained manner crucial for microbial inhibition. Tobramycin elution characteristics indicate an initial release maximum during the first 24 h that diminishes gradually several days after impregnation. The copious tobramycin quantity eluted from the VITOSS/silicate-xerogel systems is attributed to various factors: the intrinsic ultraporosity and hydrophilicity of VITOSS, the ability of tobramycin to completely dissolve in aqueous media, tobramycin complexation with highly polar SO(4) (2-) salts that further assist dissolution, and ionic exchanges between VITOSS and the environment. Silicate-xerogel-encapsulated VITOSS eluted 60.65 and 61.31% of impregnated tobramycin, whereas non-silicate-xerogel-encapsulated VITOSS eluted approximately one-third less impregnated tobramycin, at 21.53 and 23.60%. These results suggest that silicate xerogel optimizes tobramycin elution because of its apparent biodegradability. This mechanism occurs through xerogel superficial acidic sites undergoing exchanges with various ions present in the leaching buffer. Tobramycin elution kinetics were evaluated, and demonstrate that first-order elution rate constants are considerably less when silicate xerogels are employed, following a more uniform exponential decay-type mechanism, thus bolstering controlled release. Overall, tobramycin elution rates adhere to linear-type Higuchi release profiles. Elution rate constants are initially first order, and taper into zero-order elution kinetics in the latter stages of

  19. 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.

  20. Clinical application of iodine-eluting stent in patients with advanced esophageal cancer

    PubMed Central

    DAI, ZHENBO; ZHOU, DEJUN; HU, JIANZHANG; ZHANG, LEI; LIN, YUNSHOU; ZHANG, JING; LI, FENGLING; LIU, PENG; LI, HUA; CAO, FULIANG

    2013-01-01

    The aim of the present study was to compare the clinical effectiveness of an iodine-eluting stent with a conventional stent in patients with advanced esophageal cancer. Patients with malignant esophageal cancer were randomly assigned to receive a conventional stent (group A) or an iodine-eluting stent (group B). Following implantation, the relief from dysphagia, survival time, routine blood tests, thyroid function examination and complications were compared in the two groups. Groups A and B consisted of 36 and 31 patients, respectively. The mean value that the dysphagia score decreased by was significantly lower in group A (0.83) compared with group B (1.65). The median survival time was longer in group B compared with group A (P=0.0022). No significant differences were observed in the severe complications between the two groups (P=0.084). The iodine-eluting esophageal stent is a relatively safe, feasible and effective treatment for malignant esophageal strictures. PMID:24137396

  1. Sperm elution: an improved two phase recovery method for sexual assault samples.

    PubMed

    Hulme, Paul; Lewis, Jennie; Davidson, Geraldine

    2013-03-01

    This report describes the validation of a two phase cell recovery technique for the elution of two common cell types, epithelia and spermatozoa, from frequently examined items submitted as part of sexual assault casework. Furthermore, separation of cell types prior to microscopic examination of cell pellets improves the scientist's confidence in observing and scoring spermatozoa that may be present. During the validation, Orchid Cellmark's Sperm Elution© method consistently recovered a greater number of spermatozoa from simulated sexual assault items and swabs taken following consensual sexual intercourse compared to a water extraction technique. On average the Sperm Elution method recovered over twice the number of spermatozoa compared to the water method. The ability to separate the cell types present allows a rapid microscope slide search for spermatozoa and faster DNA extraction protocol in comparison to Cellmark's previous preferential method. Copyright © 2012 Forensic Science Society. Published by Elsevier Ireland Ltd. All rights reserved.

  2. 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

  3. 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.

  4. Stent Coating Integrity of Durable and Biodegradable Coated Drug Eluting Stents.

    PubMed

    Yazdani, Saami K; Sheehy, Alexander; Pacetti, Stephen; Rittlemeyer, Brandon; Kolodgie, Frank D; Virmani, Renu

    2016-10-01

    Coatings consisting of a polymer and drug are widely used in drug-eluting stents (DES) and are essential in providing programmable drug release kinetics. Among other factors, stent coating technologies can influence blood compatibility, affect acute and sub-acute healing, and potentially trigger a chronic inflammatory response. The aim of this study was to investigate the short-term (7 and 28 days) and long-term (90 and 180 days) coating integrity of the Xience Prime Everolimus-Eluting Stent (EES), Resolute Zotarolimus-Eluting Stent (ZES), Taxus Paclitaxel-Eluting Stent (PES), and Nobori Biolimus A9-Eluting Stent (BES) in a rabbit ilio-femoral stent model. Stented arteries (n = 48) were harvested and the tissue surrounding the implanted stents digested away with an enzymatic solution. Results demonstrated that the majority of struts of EES were without any coating defects with a few struts showing minor defects. Similarly, for the ZES, most of the struts were without coating defects at all time points except at 180 days. The majority of PES demonstrated mostly webbing and uneven coating. In the BES group, the majority of strut coating showed polymer cracking. Overall, the EES and ZES had fewer coating defects than the PES and BES. Coating defects, however increase over time for the ZES, whereas the percent of coating irregularities remained constant for the EES. These results provide, for the first time, a comparison of the long-term durability of these drug-eluting stent coatings in vivo. © 2016, Wiley Periodicals, Inc.

  5. The effect of temperature on bisphenol: an elution from dental resins.

    PubMed

    Atabek, Didem; Aydintug, Itir; Alaçam, Alev; Berkkan, Aysel

    2014-09-01

    Bisphenol A (BPA) elution from baby bottles into content has been of great public interest and debate in recent year. Uncontrolled BPA elution due to temperature increase may create a risk factor for human health. However, dental resins that are used in pediatric dentistry also have BPA derivatives. The aim of this study is to evaluate BPA elution from dental resins and to determine the effect of temperature increase on this elution. Four dental resins containing BPA derivatives (Filtek Z250, Filtek Supreme XT, Fissurit FX, and Admira) and a control group (BPA free G-aenial) were used in this study. Each specimen was stored in 2 ml of 75% ethanol-water solution at 37°C. Water at a temperature of 59°C ± 1°C (preferred temperature of hot drinks) was added to the study samples at certain time intervals (1, 6, 24 hours and 2, 3, 4, 5 and 6 days). The methanol samples were analyzed using high-performance liquid chromatography (HPLC). Data was analyzed using multivariate and repeated measures analysis of variance (p < 0.05). The study samples generally eluted more BPA than the control samples (p < 0.05). The greatest amount of BPA for an individual time period was measured after 6 hours for the groups A to D; the same was found after 24 hours for group E. While the BPA elution levels evaluated in the study samples were more than control samples, all measured values were under the reference levels and the amounts do not constitute a risk. Resin-based dental materials can act as a source of BPA (within safety margins), especially when they react with hot water.

  6. The effect of storage medium on the elution of monomers from composite materials.

    PubMed

    Polydorou, Olga; Huberty, Catherine; Wolkewitz, Martin; Bolek, Richard; Hellwig, Elmar; Kümmerer, Klaus

    2012-01-01

    The aim of this study was to evaluate the effect of four different storage media on the elution of monomers from two composite materials. Samples (n = 10, diameter: 4.5 mm, thickness: 2 mm) of two different composite materials (Ceram X™ & Filtek™ Supreme XT) were stored after polymerization in four different media (NaCl, saliva, ethanol 75% & acetone) for 24 h, 7 days, and 28 days. From the storage medium of each tested time period, samples were prepared and analyzed by LC-MS/MS, for the elution of BisGMA, TEGDMA, HEMA, Bisphenol A, and two types of UDMA. No monomers were detected in the samples of Ceram X™, independently of the storage medium used. In the samples of Filtek™ Supreme XT, no Bisphenol A, HEMA, and UDMA 1 were found. BisGMA was detected only in the ethanol and acetone samples. The amount of BisGMA eluted in acetone was significant higher compared with ethanol 75% (p < 0.0001). TEGDMA was the only monomer that could be detected in all tested storage media. Storage in acetone resulted in higher release of TEGDMA when compared with other media. The amount of TEGDMA released in saliva was similar to the one released in ethanol 75%. It can be concluded that acetone is not a suitable medium for elution experiments and although ethanol 75% can simulate saliva concerning the elution of TEGDMA, it does not represent a laboratory substitute of saliva with respect to the elution of monomers like BisGMA. Copyright © 2011 Wiley Periodicals, Inc.

  7. Angioscopic assessment of arterial repair following biodegradable polymer-coated biolimus A9-eluting stent implantation. - Comparison with durable polymer-coated sirolimus-eluting stent-.

    PubMed

    Awata, Masaki; Uematsu, Masaaki; Sera, Fusako; Ishihara, Takayuki; Watanabe, Tetsuya; Fujita, Masashi; Onishi, Toshinari; Iida, Osamu; Ishida, Yoshio; Nanto, Shinsuke; Nagata, Seiki

    2011-01-01

    Second-generation drug-eluting stents (DES) are expected to show better arterial repair than older DES. We angioscopically compared the biodegradable polymer-coated biolimus A9-eluting stent (BES) and durable polymer-coated sirolimus-eluting stent (SES) to explore differences in arterial repair. Angioscopy was performed 9 ± 1 months after 15 BES and 16 SES were implanted initially in the native coronary artery. Heterogeneity of neointimal coverage (NIC) as well as the dominant NIC grade was examined. NIC was defined as: grade 0 = fully visible struts; grade 1 = struts bulging into the lumen, but covered; grade 2 = embedded, but translucent struts; grade 3 = invisible struts. Heterogeneity was judged when the NIC grade varied ≥ 1. In-stent late loss (0.06 ± 0.23 vs. 0.07 ± 0.18 mm, P = 0.80), and dominant NIC grade (1.5 ± 0.8 vs. 1.3 ± 0.7, P = 0.45) were similar for BES and SES. Within the stents, NIC was more heterogeneous in SES than in BES (P = 0.035). 80% of BES showed homogeneous NIC, while 56% of SES had heterogeneous NIC. BES showed limited late loss similar to that for SES. Nonetheless, the NIC with BES was more homogeneous than that with SES. Biodegradable polymer-coated BES may have an advantage in homogeneous NIC.

  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. 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

  10. Drug-eluting stents in the management of peripheral arterial disease.

    PubMed

    Bosiers, Marc; Cagiannos, Catherine; Deloose, Koen; Verbist, Jürgen; Peeters, Patrick

    2008-01-01

    Since major meta-analyses of randomized controlled trials in interventional cardiology showed the potential of drug-eluting stents in decreasing restenosis and reintervention rates after coronary artery stenting, one of the next steps in the treatment of arterial occlusive disease is the transfer of the active coating technology towards peripheral arterial interventions. In this manuscript, we aim to provide a literature overview on available peripheral (lower limb, renal, and supra-aortic) drug-eluting stent applications, debate the cost implications, and give recommendations for future treatment strategies.

  11. Drug-eluting stents in the management of peripheral arterial disease

    PubMed Central

    Bosiers, Marc; Cagiannos, Catherine; Deloose, Koen; Verbist, Jürgen; Peeters, Patrick

    2008-01-01

    Since major meta-analyses of randomized controlled trials in interventional cardiology showed the potential of drug-eluting stents in decreasing restenosis and reintervention rates after coronary artery stenting, one of the next steps in the treatment of arterial occlusive disease is the transfer of the active coating technology towards peripheral arterial interventions. In this manuscript, we aim to provide a literature overview on available peripheral (lower limb, renal, and supra-aortic) drug-eluting stent applications, debate the cost implications, and give recommendations for future treatment strategies. PMID:18827906

  12. Longitudinal deformation of a third generation zotarolimus eluting stent: “The concertina returns!”

    PubMed Central

    Panoulas, Vasileios F; Demir, Ozan M; Ruparelia, Neil; Malik, Iqbal

    2017-01-01

    In the current case series we describe two cases of longitudinal stent deformation in ostial lesions treated with a new generation zotarolimus eluting stent and review current literature on longitudinal stent deformation. Historically not a common occurrence, longitudinal deformation occurred mainly in Promus Element everolimus eluting stents, which had only two rather than the commonly used 3 links between stent rings. Longitudinal deformation commonly occurs secondary to compression of the proximal edge of the stent by either the guide catheters, or intravascular balloons and imaging catheters. The degree of deformation however, depends on the longitudinal strength and design of the stent. PMID:28163838

  13. Two Cases of Immediate Stent Fracture after Zotarolimus-Eluting Stent Implantation

    PubMed Central

    Lee, Pil Hyung; Lee, Seung-Whan; Lee, Jong-Young; Kim, Young-Hak; Lee, Cheol Whan; Park, Duk-Woo; Park, Seong-Wook

    2015-01-01

    Drug-eluting stent (DES) implantation is currently the standard treatment for various types of coronary artery disease. However, previous reports indicate that stent fractures, which usually occur after a period of time from the initial DES implantation, have increased during the DES era; stent fractures can contribute to unfavorable events such as in-stent restenosis and stent thrombosis. In our present report, we describe two cases of zotarolimus-eluting stent fracture: one that was detected six hours after implementation, and the other case that was detected immediately after deployment. Both anatomical and technical risk factors contributed to these unusual cases of immediate stent fracture. PMID:25653706

  14. Bare metal or drug-eluting stent implantation in last remaining vessel PCI? A serious dilemma.

    PubMed

    Zhang, Lei; Zhu, Jianhua; Kiemeneij, Ferdinand

    2009-04-01

    This case report describes the treatment of an old male diabetic patient with last remaining vessel coronary artery disease and poor left ventricular function. In presence of an old occlusion of the left main coronary artery, a subtotal stenosis of a dominant right coronary artery required angioplasty. After ample consideration it was decided to implant a bare metal stent (BMS) instead of a drug-eluting stent (DES). The major reason was the fear for early discontinuation of clopidogrel in case a drug-eluting stent was placed. The procedure and follow-up are described followed by an overview of current literature concerning similar pathology.

  15. Usefulness of Drug-Eluting Balloons for Bare-Metal and Drug-Eluting In-Stent Restenosis (from the RIBS IV and V Randomized Trials).

    PubMed

    Alfonso, Fernando; Pérez-Vizcayno, María José; García Del Blanco, Bruno; García-Touchard, Arturo; López-Mínguez, José-Ramón; Sabaté, Manel; Zueco, Javier; Melgares, Rafael; Hernández, Rosana; Moreno, Raul; Domínguez, Antonio; Sanchís, Juan; Moris, Cesar; Moreu, José; Cequier, Angel; Romaguera, Rafael; Rivero, Fernando; Cuesta, Javier; Gonzalo, Nieves; Jiménez-Quevedo, Pilar; Cárdenas, Alberto; Fernández, Cristina

    2017-04-01

    Treatment of patients with drug-eluting stent (DES) in-stent restenosis (ISR) is particularly challenging. We sought to compare results of drug-eluting balloons in patients with DES-ISR with those in patients with bare-metal stent (BMS) ISR. A pooled analysis of the Restenosis Intra-Stent: Drug-Eluting Balloon versus Everolimus-Eluting Stent IV and V randomized trials was performed. Both trials had identical inclusion and exclusion criteria. Results of drug-eluting balloons in 95 patients with BMS-ISR and 154 patients with DES-ISR were compared. Patients with DES-ISR were more frequently diabetics, presented more often as an acute coronary syndrome and had more severe lesions and more frequently a focal pattern, including edge-ISR. Late angiographic findings (92% of eligible patients), including minimal lumen diameter (1.80 ± 0.6 vs 2.01 ± 0.6 mm, p = 0.001; absolute mean difference 0.21 mm; 95% confidence interval 0.04 to 0.38; p = 0.014) and restenosis rate (19% vs 9.5%, p <0.05) were poorer in DES-ISR. Results were consistent across 10 prespecified subgroups. Moreover, on multiple linear regression analysis, minimal lumen diameter at follow-up remained significantly smaller in patients with DES-ISR after adjusting for potential confounders (adjusted absolute mean difference 0.17 mm; 95% confidence interval 0.04 to 0.41; p = 0.019). Finally, at 1-year clinical follow-up (100% of patients), rates of target vessel revascularization (16% vs 6%, p = 0.02) and of the main combined clinical end point (18% vs 8%, p = 0.03) were significantly higher in patients treated for DES-ISR. In conclusion, this study confirms the efficacy of DEB for patients with ISR. However, the long-term clinical and angiographic results of DEB are poorer in patients with DES-ISR than in those with BMS-ISR. (ClinicalTrials.govIdentifier:NCT01239953&NCT01239940).

  16. 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

  17. Long-term outcome of the unrestricted use of everolimus-eluting stents compared to sirolimus-eluting stents and paclitaxel-eluting stents in diabetic patients: the Bern-Rotterdam diabetes cohort study.

    PubMed

    Simsek, C; Räber, L; Magro, M; Boersma, E; Onuma, Y; Stefanini, G G; Zanchin, T; Kalesan, B; Wenaweser, P; Jüni, P; van Geuns, R J; van Domburg, R T; Windecker, S; Serruys, P W J C

    2013-12-05

    Newer generation everolimus-eluting stents (EES) improve clinical outcome compared to early generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). We investigated whether the advantage in safety and efficacy also holds among the high-risk population of diabetic patients during long-term follow-up. Between 2002 and 2009, a total of 1963 consecutive diabetic patients treated with the unrestricted use of EES (n=804), SES (n=612) and PES (n=547) were followed throughout three years for the occurrence of cardiac events at two academic institutions. The primary end point was the occurrence of definite stent thrombosis. The primary outcome occurred in 1.0% of EES, 3.7% of SES and 3.8% of PES treated patients ([EES vs. SES] adjusted HR=0.58, 95% CI 0.39-0.88; [EES vs. PES] adjusted HR=0.29, 95% CI 0.13-0.67). Similarly, patients treated with EES had a lower risk of target-lesion revascularization (TLR) compared to patients treated with SES and PES ([EES vs. SES], 5.6% vs. 11.5%, adjusted HR=0.68, 95% CI: 0.55-0.83; [EES vs. PES], 5.6% vs. 11.3%, adjusted HR=0.51, 95% CI: 0.33-0.77). There were no differences in other safety end points, such as all-cause mortality, cardiac mortality, myocardial infarction (MI) and MACE. In diabetic patients, the unrestricted use of EES appears to be associated with improved outcomes, specifically a significant decrease in the need for TLR and ST compared to early generation SES and PES throughout 3-year follow-up. © 2013.

  18. Comparison of Durable-Polymer Zotarolimus-Eluting and Biodegradable-Polymer Biolimus-Eluting Coronary Stents in Patients With Coronary Artery Disease: 3-Year Clinical Outcomes in the Randomized SORT OUT VI Trial.

    PubMed

    Raungaard, Bent; Christiansen, Evald H; Bøtker, Hans Erik; Hansen, Henrik S; Ravkilde, Jan; Thuesen, Leif; Aarøe, Jens; Villadsen, Anton B; Terkelsen, Christian J; Krusell, Lars R; Maeng, Michael; Kristensen, Steen D; Veien, Karsten T; Hansen, Knud N; Junker, Anders; Madsen, Morten; Andersen, Søren L; Jensen, Svend E; Jensen, Lisette O

    2017-02-13

    The authors sought to compare the safety and efficacy of the biocompatible durable-polymer zotarolimus-eluting stent with the biodegradable-polymer biolimus-eluting stent in unselected coronary patients. Biodegradable-polymer biolimus-eluting stents are superior to first-generation durable-polymer drug-eluting stents in long-term randomized all-comer trials. Long-term data comparing them to second-generation durable-polymer drug-eluting stents are lacking. The study was a randomized, multicenter, all-comer, noninferiority trial in patients with chronic stable coronary artery disease or acute coronary syndromes and at least 1 coronary artery lesion requiring treatment with a drug-eluting stent. Endpoints included major adverse cardiac events (MACE), a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target lesion revascularization); the individual endpoints of MACE; all-cause mortality; any myocardial infarction; target vessel revascularization; and definite or probable stent thrombosis at 36 months. From March 2011 to August 2012, 2,999 patients were randomly assigned (1:1) to receive either the zotarolimus-eluting (1,502 patients) or the biolimus-eluting (1,497 patients) stent. At 3-year follow-up, MACE occurred in 128 (8.6%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 144 (9.6%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.36). Occurrence of cardiac death (2.7% vs. 3.4%), myocardial infarction not clearly attributable to a non-target lesion (2.7% vs. 2.5%), and target lesion revascularization (5.4% vs. 5.5%) did not differ significantly between the 2 groups. Definite very late stent thrombosis occurred in 6 (0.4%) patients assigned to the durable-polymer zotarolimus-eluting stent and in 10 (0.7%) assigned to the biodegradable-polymer biolimus-eluting stent (p = 0.33). At 3-year follow-up, the durable-polymer zotarolimus-eluting stent

  19. Does antibiotic elution from PMMA beads deteriorate after 1-year shelf storage?

    PubMed

    Balsamo, Luke H; Whiddon, David R; Simpson, R Bruce

    2007-09-01

    Antibiotic-impregnated polymethylmethacrylate beads are widely used as an adjunct in the treatment of orthopaedic infections. Because there is no commercially available bead in the United States, surgeons must manufacture bead sets at the time of implantation. This can be time consuming and wasteful. We hypothesized antibiotic-impregnated beads would maintain consistent elution for up to 1 year after manufacturing and storage. Tobramycin-impregnated antibiotic beads were manufactured using a bead mold. The antibiotic was either hand-mixed into the polymethylmethacrylate powder (1.2 g/40 g) or came premixed from the factory (1 g/40 g). Packages of beads were gas-sterilized and stored at room temperature. Beads were tested at 0, 1, 2, 3, 6, and 12 months. Antibiotic levels in the eluent from each day of the month were measured. We were unable to detect any difference in the amount of antibiotic elution between beads tested immediately after manufacture and beads manufactured and stored for 6 or 12 months. Beads with hand-mixed antibiotics eluted higher levels of antibiotics than the beads prepared with factory-mixed antibiotics. We conclude antibiotic beads can be made, sterilized, and used after 1 year of storage with no deleterious effect on antibiotic elution characteristics.

  20. The elution of colistimethate sodium from polymethylmethacrylate and calcium phosphate cement beads.

    PubMed

    Waterman, Paige; Barber, Melissa; Weintrob, Amy C; VanBrakle, Regina; Howard, Robin; Kozar, Michael P; Andersen, Romney; Wortmann, Glenn

    2012-06-01

    Gram-negative bacilli resistance to all antibiotics, except for colistimethate sodium (CMS), is an emerging healthcare concern. Incorporating CMS into orthopedic cement to treat bone and soft-tissue infections due to these bacteria is attractive, but the data regarding the elution of CMS from cement are conflicting. The in vitro analysis of the elution of CMS from polymethylmethacrylate (PMMA) and calcium phosphate (CP) cement beads is reported. PMMA and CP beads containing CMS were incubated in phosphate-buffered saline and the eluate sampled at sequential time points. The inhibition of the growth of a strain of Acinetobacter baumannii complex by the eluate was measured by disk diffusion and microbroth dilution assays, and the presence of CMS in the eluate was measured by mass spectroscopy. Bacterial growth was inhibited by the eluate from both PMMA and CP beads. Mass spectroscopy demonstrated greater elution of CMS from CP beads than PMMA beads. The dose of CMS in PMMA beads was limited by failure of bead integrity. CMS elutes from both CP and PMMA beads in amounts sufficient to inhibit bacterial growth in vitro. The clinical implications of these findings require further study.

  1. 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

    2010-06-05

    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. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  2. 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.

  3. Optimized pH method for DNA elution from buccal cells collected in Whatman FTA cards.

    PubMed

    Lema, Carolina; Kohl-White, Kendra; Lewis, Laurie R; Dao, Dat D

    2006-01-01

    DNA is the most accessible biologic material for obtaining information from the human genome because of its molecular stability and its presence in every nucleated cell. Currently, single nucleotide polymorphism genotyping and DNA methylation are the main DNA-based approaches to deriving genomic and epigenomic disease biomarkers. Upon the discontinuation of the Schleicher & Schuell IsoCode product (Dassel, Germany), which was a treated paper system to elute DNA from several biologic sources for polymerase chain reaction (PCR) analysis, a high-yielding DNA elution method was imperative. We describe here an improved procedure of the not fully validated Whatman pH-based elution protocol. Our DNA elution procedure from buccal cells collected in Whatman FTA cards (Whatman Inc., Florham Park, NJ) yielded approximately 4 microg of DNA from a 6-mm FTA card punch and was successfully applied for HLA-DQB1 genotyping. The genotypes showed complete concordance with data obtained from blood of the same subjects. The achieved high DNA yield from buccal cells suggests a potential cost-effective tool for genomic and epigenomic disease biomarkers development.

  4. Chronic total occlusion successfully treated with a bioresorbable everolimus-eluting vascular scaffold

    PubMed Central

    Mattesini, Alessio; Dall'Ara, Gianni; Mario, Carlo Di

    2014-01-01

    Fully bioresorbable vascular scaffolds (BVS) are a new approach to the percutaneous treatment of coronary artery disease. The BVS have not yet been fully tested in complex lesions, including chronic total occlusion (CTO). We report a CTO case successfully treated with a second-generation bioabsorbable drug-eluting scaffold. PMID:25061461

  5. A comparison of two methods of eluting insect DNA from Flinders Technology Associates Cards

    USDA-ARS?s Scientific Manuscript database

    Flinders Technology Associates (FTA) technology lyses cells and stabilizes DNA for room-temperature storage in a single step but it has been infrequently used with arthropods. One possible reason is the paucity of quick and inexpensive protocols to subsequently elute the DNA from the card matrix. Th...

  6. 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 ...

  7. Balloon angioplasty of the bilateral renal arteries by Takayasu arteritis with a paclitaxel-eluting balloon.

    PubMed

    Hecht, Tobias; Esmaeili, Anoosh; Behnke-Hall, Kachina

    2015-10-01

    We report about a 12-year-old girl who presented with a blood pressure difference between the extremities with the suspicion of an aortic coarctation. After imaging and laboratory tests, the diagnosis of Takayasu arteritis was made. Owing to persistent arterial hypertension despite medical treatment, we initiated a treatment with a balloon angioplasty of the renal arteries with an eluting balloon.

  8. Nisin adsorption to polyethylene oxide layers and its resistance to elution in the presence of fibrinogen

    PubMed Central

    Ryder, Matthew P.; Schilke, Karl F.; Auxier, Julie A.; McGuire, Joseph; Neff, Jennifer A.

    2010-01-01

    The adsorption and elution of the antimicrobial peptide nisin at silanized silica surfaces coated to present pendant polyethylene oxide chains was detected in situ by zeta potential measurements. Silica microspheres were treated with trichlorovinylsilane to introduce hydrophobic vinyl groups, followed by self assembly of the polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) triblock surfactant Pluronic® F108, or an F108 derivative with nitrilotriacetic acid endgroups. Triblock-coated microspheres were γ-irradiated to covalently stabilize the PPO-surface association. PEO layer stability was evaluated by triblock resistance to elution by SDS, and layer uniformity was evaluated by fibrinogen repulsion. Introduction of nisin to uncoated or triblock-coated microspheres produced a significant positive change in surface charge (zeta potential) as a result of adsorption of the cationic peptide. In sequential adsorption experiments, the introduction of fibrinogen to nisin-loaded triblock layers caused a decrease in zeta potential that was consistent with partial elution of nisin and/or preferential location of fibrinogen at the interface. This change was substantially more pronounced for uncoated than triblock-coated silica, indicating that the PEO layer offers enhanced resistance to nisin elution. PMID:20619847

  9. Surface induced three-peak elution behavior of a monoclonal antibody during cation exchange chromatography.

    PubMed

    Guo, Jing; Creasy, Arch D; Barker, Gregory; Carta, Giorgio

    2016-11-25

    A monoclonal antibody exhibits a two- or three-peak elution behavior when loaded on the CEX resin POROS XS and eluted with a salt gradient. Two peaks are observed without a hold step while a third more strongly retained peak becomes noticeable with a hold time as low as 10min. As the hold time is increased further, the first peak gradually disappears, the second peak initially increases and then decreases, and the third peak continuously increases. Dynamic light scattering shows that the third peak contains significant levels of aggregates formed in the column. Circular dichroism, HX-MS analyses of the eluted fraction, in-line fluorescence detection, and bound-state HX-MS analysis indicate that the aggregates derive from an unfolded intermediate that is slowly formed while the protein is bound to the resin. Aggregate formation does not occur on a different CEX resin, Nuvia HR-S, with similar particle size but with a more homogenous structure or when the sodium acetate load buffer is replaced with arginine acetate. The two early eluting peaks observed for POROS XS regardless of hold time are shown to comprise exclusively monomeric species. A set of biophysical measurements as well as mechanistic modeling support the hypothesis that these two peaks form as a result of the presence of weak and strong binding sites on the resin having, respectively, fast and slow binding kinetics.

  10. 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 ...

  11. Some insights on the description of gradient elution in reversed-phase liquid chromatography.

    PubMed

    Baeza-Baeza, Juan José; García-Álvarez-Coque, María Celia

    2014-09-01

    The so-called "fundamental equation for gradient elution" has been used for modeling the retention in gradient elution. In this approach, the instantaneous retention factor (k) is expressed as a function of the change in the modifier content (φ(ts )), ts being the time the solute has spent in the stationary phase. This approach can only be applied at constant flow rate and with gradients where the elution strength depends on the column length following a f(t-l/u) function, u being the linear mobile phase flow rate, and l the distance from the column inlet to the location where the solute is at time t measured from the beginning of the gradient. These limitations can be solved by using the here called "general equation for gradient elution", where k is expressed as a function of φ(t,l). However, this approach is more complex. In this work, a method that facilitates the integration of the "general equation" is described, which allows an approximate analytical solution with the quadratic retention model, improving the predictions offered by the "linear solvent strength model." It also offers direct information about the changes in the instantaneous modifier content and retention factor, and gives a meaning to the gradient retention factor.

  12. A new mixed-mode model for interpreting and predicting protein elution during isoelectric chromatofocusing.

    PubMed

    Choy, Derek Y C; Creagh, A Louise; von Lieres, Eric; Haynes, Charles

    2014-05-01

    Experimental data are combined with classic theories describing electrolytes in solution and at surfaces to define the primary mechanisms influencing protein retention and elution during isoelectric chromatofocusing (ICF) of proteins and protein mixtures. Those fundamental findings are used to derive a new model to understand and predict elution times of proteins during ICF. The model uses a modified form of the steric mass action (SMA) isotherm to account for both ion exchange and isoelectric focusing contributions to protein partitioning. The dependence of partitioning on pH is accounted for through the characteristic charge parameter m of the SMA isotherm and the application of Gouy-Chapman theory to define the dependence of the equilibrium binding constant Kbi on both m and ionic strength. Finally, the effects of changes in matrix surface pH on protein retention are quantified through a Donnan equilibrium type model. By accounting for isoelectric focusing, ion binding and exchange, and surface pH contributions to protein retention and elution, the model is shown to accurately capture the dependence of protein elution times on column operating conditions.

  13. The chromatographic co-elution of dihydrodehydrodiconiferyl alcohol monopyranose with eleutheroside E in Eleutherococcus senticosus: implications for eleutheroside E assays.

    PubMed

    Gaffney, B T; Hügell, H M; Rich, P A

    2004-01-01

    During a quantification assay of the constituents of Eleutherococcus senticosus by reverse-phase HPLC using acetonitrile:water gradient elution, it was observed that a recently reported component, dihydrodehydrodiconiferyl alcohol monopyranose, co-eluted with eleutheroside E. The implications of this finding for researchers and the herbal medicine industry are discussed. C

  14. Preparation, characterization and anticoagulation of curcumin-eluting controlled biodegradable coating stents.

    PubMed

    Pan, Ch J; Tang, J J; Weng, Y J; Wang, J; Huang, N

    2006-11-01

    Curcumin is pharmaceutically active in many ways, having properties including anticoagulation, anti-proliferation, anti-inflammatory, and may be used to fabricate drug-eluting stents to treat in-stent restenosis after stent implantation. Here we describe our investigations of curcumin-eluting PLGA coatings formed using the biodegradable polymer PLGA (polylactic acid-co-glycolic acid) as drug carrier and uniformly fabricated on the surface of 316L stainless steel stents by an ultrasonic spray method. Three doses were explored--low dose ( approximately 140 microg per stent or 115 microg/cm(2)), moderate dose ( approximately 280 microg per stent or 230 microg/cm(2)), and high dose ( approximately 490 microg per stent or 408 microg/cm(2)). Pre- and post-expansion morphologies of the stent coating were examined by optical microscopy (OM) and scanning electron microscopy (SEM), indicating that the coating not only was very smooth and uniform but also had the ability to withstand the compressive and tensile strains imparted without cracking from the stent during the expansion process. Atomic force microscopy (AFM) images indicated the topography of the PLGA-only and moderate dose curcumin-eluting stent that showed an average roughness below 1 nm; no drug particles could be seen on the stent surface, indicating that curcumin can be mixed with PLGA at the molecular level using an ultrasonic atomization spray method. The structure of the coating films was characterized by Fourier Transform Infrared (FTIR) spectroscopy and X-ray electron spectroscopy (XPS), with results suggesting that there was no chemical reaction between curcumin and the drug. The results of in vitro measurements of drug release from curcumin-eluting stents showed that all the curcumin-eluting stents studied exhibited a nearly linear sustained-release profile with no significant burst releases within the measurement period. The in vitro anticoagulation behavior of curcumin-eluting stents was investigated

  15. Size- and density-dependent elution of normal and pathological red blood cells by gravitational field-flow fractionation.

    PubMed

    Cardot, P J; Elgéa, C; Guernet, M; Godet, D; Andreux, J P

    1994-04-01

    Elution of normal and pathological human red blood cells (RBCs) was performed by gravitational field-flow fractionation (GFFF). The reproducibility of the retention factor was lower than 10% and elution at high and low flow-rates confirmed the existence of "lifting forces". No direct correlation between size and retention was observed for normal RBCs in the absence of density information. Elution of pathological human RBCs, known to be modified in shape, density and rigidity, was performed. The elution parameters confirmed that the retention mechanism of RBCs is at least density dependent but that other factors can be involved, such as shape or deformity. Moreover, peak profile description parameters (standard deviation and asymmetry) can be qualitatively related to some biophysical parameters. Numerous elution characteristics can be linked to cell properties described in the literature and although GFFF appeared to have limited capabilities in terms of size analysis it appeared to be a versatile tool for studying cell biophysical characteristics.

  16. Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin.

    PubMed

    Slane, Joshua; Gietman, Bradley; Squire, Matthew

    2017-09-06

    Two-stage revision treatment of prosthetic joint infection (PJI) frequently employs the use of a temporary bone cement spacer loaded with multiple antibiotic types. Tobramycin and vancomycin are commonly used antibiotics in cement spacers, however, there is no consensus on the relative concentrations and combinations that should be used. Therefore, the purpose of this study was to investigate the influence of dual antibiotic loading on the total antibiotic elution and compressive mechanical properties of acrylic bone cement. Varying concentrations of tobramycin (0-3 g) and vancomycin (0-3 g) were added either alone or in combination to acrylic cement (Palacos R), resulting in 12 experimental groups. Samples were submerged in 37°C saline for 28 d and sampled at specific time points. The collected eluent was analyzed to determine the cumulative antibiotic release. In addition, the cement's compressive mechanical properties and porosity were characterized. Interestingly, the cement with the highest concentration of antibiotics did not possess the best elution properties. Cement samples containing both 3 g of tobramycin and 2 g vancomycin demonstrated the highest cumulative antibiotic release after 28 d, which was coupled with a significant decrease in the mechanical properties and an increased porosity. The collected data also suggests that tobramycin elutes more effectively than vancomycin from cement. In conclusion, this study demonstrates that high antibiotic loading in cement does not necessarily lead to enhanced antibiotic elution. Clinically this information may be used to optimize cement spacer antibiotic loading so that both duration and amount of antibiotics eluted are optimized. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  17. 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.

  18. Establishing conditions for the storage and elution of rabies virus RNA using FTA(®) cards.

    PubMed

    Sakai, Takeo; Ishii, Ayako; Segawa, Takao; Takagi, Yukihiko; Kobayashi, Yuki; Itou, Takuya

    2015-04-01

    The Flinders Technology Associates filter paper cards (FTA(®) cards) can be used to store nucleic acid from various samples and are easily portable. However, RNA is physicochemically unstable compared with DNA, and appropriate methods have not been established for storage and extraction of RNA from FTA(®) cards. The present study investigated the optimum conditions for storage and elution of viral RNA (vRNA) using rabies virus (RABV) applied to FTA(®) cards. When TE buffer was used, the elution rates of vRNA increased with the length of the elution time. When the cards were stored at -80 °C or -20 °C, vRNA was stable over 3 months. Degradation of vRNAs occurred following storage at 4 °C and room temperature, suggesting that RNA should be extracted from cards as soon as possible if no freezer is available. When we tried to amplify vRNA from RABV-infected animal brains applied to FTA(®) cards and stored at -80 °C for 6 months, we did not detect any amplified products with the primer set for 964 bp of RABV N gene. However, we were able to detect amplified products by increasing the elution time of vRNA from FTA(®) cards from 30 min to 24 hr or by changing the primer sets to amplify 290 bp of N gene. Thus, we recommend extending the elution time for damaged or low concentration samples in FTA(®) cards.

  19. Elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate beads in vitro.

    PubMed

    Tulipan, Rachel J; Phillips, Heidi; Garrett, Laura D; Dirikolu, Levent; Mitchell, Mark A

    2016-11-01

    OBJECTIVE To characterize the elution of platinum from carboplatin-impregnated calcium sulfate hemihydrate (CSH) beads in vitro. SAMPLE 60 carboplatin-impregnated CSH beads and 9 CSH beads without added carboplatin (controls). PROCEDURES Carboplatin-impregnated CSH beads (each containing 4.6 mg of carboplatin [2.4 mg of platinum]) were placed into separate 10-mL plastic tubes containing 5 mL of PBSS in groups of 1, 3, 6, or 10; 3 control beads were placed into a single tube of PBSS at the same volume. Experiments were conducted in triplicate at 37°C and a pH of 7.4 with constant agitation. Eluent samples were collected at 1, 2, 3, 6, 12, 24, and 72 hours. Samples were analyzed for platinum content by inductively coupled plasma-mass spectrometry. RESULTS The mean concentration of platinum released per carboplatin-impregnated bead over 72 hours was 445.3 mg/L. Cumulative concentrations of platinum eluted increased as the number of beads per tube increased. There was a significant difference in platinum concentrations over time, with values increasing over the first 12 hours and then declining for all tubes. There was also a significant difference in percentage of total incorporated platinum released into tubes with different numbers of beads: the percentage of eluted platinum was higher in tubes containing 1 or 3 beads than in those containing 6 or 10 beads. CONCLUSIONS AND CLINICAL RELEVANCE Carboplatin-impregnated CSH beads eluted platinum over 72 hours. Further studies are needed to determine whether implantation of carboplatin-impregnated CSH beads results in detectable levels of platinum systemically and whether the platinum concentrations eluted locally are toxic to tumor cells.

  20. Verapamil eluting stents as a possible treatment for vasospasm after subarachnoid hemorrhage.

    PubMed

    Bhambri, Pallavi; Sarvi, Ali; Wong, John H; Sundararaj, Uttandaraman; Mitha, Alim P

    2017-09-01

    The only pharmacologic prophylaxis for cerebral vasospasm after subarachnoid hemorrhage is oral nimodipine. A novel way to mitigate this risk may be to design a drug eluting stent that elutes verapamil over the time period typically associated with vasospasm. In this study, we explore different methods of coating nitinol stents with a bioabsorbable polymer and determine the release profile of various verapamil coated stents for the potential treatment of vasospasm. Nitinol stents were coated with different concentrations of poly(lactic acid-co-glycolic acid) (PLGA) in chloroform solution and using three coating techniques: dip coating, spin coating, and electrospinning. Morphology of the coatings were studied with scanning electron microscopy. 12 verapamil eluting stents were then prepared using different verapamil concentrations and coatings with different numbers of layers. Drug release behaviors were studied using UV spectroscopy for 21 days. Electrospinning at 20% w/v resulted in a smooth uniform coating without significant surface irregularities, and may be the most effective technique to coat stents. Stents with a single layer of PLGA/verapamil coating showed a two phase release profile (initial burst release followed by a slow rate of release) whereas stents with a bilayer coating showed a lower level of initial release followed by a slower sustained release phase. Development of verapamil eluting stents that elute drug over the time course typical of cerebral vasospasm, and for either immediate or prophylactic treatment, is technically feasible. Further in vitro and in vivo studies are required to determine whether this can improve the outcome of patients after subarachnoid hemorrhage. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. 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

  2. Clinical outcomes with Biolimus (A9)™ eluting stent, 'BioMatrix' in diabetic patients--interim results from multicenter post market surveillance registry in India.

    PubMed

    Seth, Ashok; Hiremath, Shirish; Dani, Sameer; Kapoor, Sunil; Jain, R K; Abhaichand, Rajpal; Trivedi, Shailendra; Kaul, Upendra; Patil, Aruna; Khemnar, Bhushan; Rangnekar, Hrishikesh

    2013-01-01

    The objective of this registry is to establish safety and efficacy of BioMatrix, BioMatrix™-Biolimus A9™ eluting stent in diabetic population in India. Diabetes mellitus is a major predisposing factor for coronary artery disease. Prognosis for diabetic population patients presenting with coronary artery disease who undergo coronary revascularization is inferior to non diabetics and remains an independent risk factor of restenosis, need for revascularization, and overall mortality. Stent thrombosis is a potential complication of first generation, permanent polymer drug-eluting stents. Biodegradable polymer is a good relief in this era and its utility in diabetic patients will be a major advantage for them. 334 patients with diabetes mellitus and requiring angioplasty, implanted with BioMatrix stent were followed at 1, 6, 12 and 24 months who entered in a multicenter registry in India. We analyzed the incidence of major adverse cardiac events (MACE) and stent thrombosis (ST) at 1, 6, 12 and 24 months. The mean age was 58.71 ± 9.2 years, 81% were males, comorbidity index was 1.6 ± 1.02, and 59.1% presented with acute coronary syndrome. The incidence of adverse event rates was: MACE 1.27%. There were no incidences of myocardial infarction (MI) and target vessel revascularization (TVR). Definite stent thrombosis occurred only in 2 patients. In this registry of diabetic population treated with BioMatrixTM-Biolimus A9TM eluting stent (BioMatrix), the reported incidence of MACE and ST were much lower than previously published results. The 1- and 2-year follow-up result supports favorable clinical outcomes of using BioMatrix stents as a suitable alternative to contemporary DES available during PCI in diabetic patients. Copyright © 2013 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  3. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Comparison of early-phase arterial repair following cobalt-chrome everolimus-eluting stent and slow-release zotarolimus-eluting stent: an angioscopic study.

    PubMed

    Ishihara, Takayuki; Iida, Osamu; Fujita, Masashi; Masuda, Masaharu; Okamoto, Shin; Nanto, Kiyonori; Kanda, Takashi; Tsujimura, Takuya; Sunaga, Akihiro; Awata, Masaki; Nanto, Shinsuke; Uematsu, Masaaki

    2017-03-02

    Whether arterial repair following implantation of drug-eluting stents (DES) of the second generation differs among stent types remains unknown. We examined 41 DES placed in 28 patients (age 72 ± 7 years, male 89%) presenting with stable angina pectoris due to de novo lesions in native coronary arteries. Coronary angioscopy was performed 4 ± 1 months after stent implantation. Patients were divided into two groups based on the DES types: 22 cobalt-chrome everolimus-eluting stents (CoCr-EES) in 13 patients and 19 slow-release zotarolimus-eluting stents (R-ZES) in 15 patients. Neointimal coverage (NIC) was graded as: grade 0, stent struts exposed; grade 1, struts bulging into the lumen, although covered; grade 2, struts embedded in the neointima, but translucent; grade 3, struts fully embedded and invisible. NIC was defined as heterogeneous when the NIC grade variation was ≥1. Presence of thrombus was also investigated. Distribution of dominant NIC grade (CoCr-EES: grade 0, 9%; grade 1, 77%; grade 2, 9%; grade 3, 5%; R-ZES: grade 0, 16%; grade 1: 47%; grade 2, 37%; grade 3, 0%, P = 0.38) and heterogeneity of NIC (P = 0.43) were similar between CoCr-EES and R-ZES groups. Existence of thrombus was not significantly different in CoCr-EES and R-ZES (18 versus 42%, P = 0.17). Arterial repair occurred without significant differences between CoCr-EES and R-ZES 4 months after implantation.

  5. Outcomes of Acute Myocardial Infarction Patients Implanted With Biodegradable Polymer Biolimus-Eluting Stents Versus New-Generation Durable Polymer Drug-Eluting Stents: A Retrospective Analysis.

    PubMed

    Choe, Jeong Cheon; Cha, Kwang Soo; Jang, Hye Yoon; Choi, Jong Hyun; Kim, Bo Won; Ahn, Jinhee; Park, Jin Sup; Lee, Hye Won; Oh, Jun-Hyok; Choi, Jung Hyun; Lee, Han Cheol; Hong, Taek Jong; Ahn, Youngkeun; Jeong, Myung Ho

    2017-09-01

    We compared outcomes between biodegradable polymer biolimus-eluting stent (BP-BES) and new-generation durable polymer drug-eluting stent (DP-DES) implantations in patients with acute myocardial infarction (MI). Among 13472 patients with acute MI in a nationwide registry, 557 (64.8%) were in the BP-BES and 303 (35.2%) in the new-generation DP-DES group following coronary reperfusion. The occurrence of major adverse cardiac events (MACE; death, MI, revascularization) and stent thrombosis was compared. Major adverse cardiac events occurred in 53 (6.2%) patients and showed similar rates between the BP-BES and new-generation DP-DES groups (all: 6.6% vs 5.9%, P = .652; propensity score [PS] matched: n = 380, 6.3% vs 5.3%, P = .623). Stent thrombosis did not differ between groups (all: 0.3% vs 0.4%, P = .892; PS matched: 0.5% vs 0.5%, P = 1.000). Major adverse cardiac event-free survival was comparable between groups (all: 93.4% vs 94.1%, log-rank P = .357; PS matched: 93.7% vs 94.7%, log-rank P = .445). Biodegradable polymer biolimus-eluting stent was not associated with MACE (all: hazard ratio [HR], 1.67; 95% confidence interval [CI], 0.75-3.74; P = 0.212; PS matched: HR, 1.05; 95% CI, 0.40-2.75; P = .915). In conclusion, in patients with acute MI, BP-BES was equivalent to the new-generation DP-DES in terms of outcomes.

  6. Comparison of endothelium-dependent and -independent vasomotor response after abluminal biodegradable polymer biolimus-eluting stent and persistent polymer everolimus-eluting stent implantation (COMPARE-IT).

    PubMed

    Puricel, Serban; Kallinikou, Zacharenia; Espinola, Jaqueline; Arroyo, Diego; Goy, Jean-Jacques; Stauffer, Jean-Christophe; Baeriswyl, Gérard; Smits, Pieter Cornelis; Cook, Stéphane; Togni, Mario

    2016-01-01

    Drug-eluting stents (DES) have been associated with local endothelial dysfunction in the segments proximal and distal to the stent (peristent segments) and increased thrombotic risk in long term follow-up. Little data exists on endothelial function post-implantation of new DES with biodegradable polymer. The aim of our study was to compare the local endothelial function assessed by exercise induced coronary vasomotion after implantation of a biolimus A9-eluting stent with biodegradable polymer (BES) with an everolimus-eluting stent with durable polymer (EES). Coronary vasomotion was evaluated with quantitative coronary angiography at rest and during supine bicycle exercise in nine patients with EES and thirteen patients with BES, 16 months after stent implantation. Mean luminal diameter of the stent, peristent segments, and of a control vessel were determined at rest, during exercise, and after the administration of nitroglycerine. The control vessel showed exercise-induced vasodilatation in both groups (EES: +6.4±5.5%, p=0.07; BES: +7.8±10.1%, p=0.07). Vasomotion in the stented vessel segment was abolished. There was exercise-induced vasoconstriction in both groups in the segments proximal (EES: -9.6±4.5%; p=0.03; BES: -4.3±5.4%, p=0.02) and distal to the stent (EES: -3.2±9.3%; p=0.41, BES -8.6±8.0%, p<0.01). Sublingual nitroglycerin was associated with maximal vasodilatation of the peristent segments in both groups. Alike DES with durable polymer, stents with a biodegradable polymer are associated with exercise-induced paradoxical coronary vasoconstriction of the peristent segments. This data suggests that endothelial dysfunction after DES implantation is not primarily caused by the durability of the polymer coating. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Comparison of Long-Term Outcomes in Real-World Patients Between Resolute Zotarilumus-Eluting and Paclitaxel-Eluting Stents in Small Vessel.

    PubMed

    Kilickesmez, Kadriye Orta; Kocaş, Betül; Yildiz, Ahmet; Coskun, Ugur; Ersanli, Murat; Arat, Alev; Gürmen, Tevfik

    2016-05-01

    To compare the long-term clinical outcomes between Resolute zotarolimus-eluting stent (R-ZES) and paclitaxel-eluting stent (PES) in patients with small coronary artery disease. Patients with a small vessel diameter are independently associated with increased risk of adverse cardiac events after drug-eluting stent implantation. A cohort of 265 patients treated with R-ZES (185 patients with 211 lesions) or PES (80 patients with 100 lesions) in small vessel (≤2.5 mm) lesions were retrospectively analyzed. The primary end point of the study was the composite of major adverse cardiac events. The secondary end points included target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis at 3 years. The baseline characteristics were similar between the 2 groups. In the R-ZES group, the mean stent diameter was smaller and the total stent length per lesion was longer. Major adverse cardiac events occurred in 8 (10%) patients who had received PES and in 7 (3.8%) patients who had received R-ZES (P = .07). The rates of 3-year TLR (2.2% vs 2.5%; P = 1.00) and TVR (5.4% vs 10.0%; P = .17) showed no statistically significant difference between the R-ZES and PES groups. The rate of stent thrombosis was 0.5% in the R-ZES group and 2.5% in the PES group (P = .21). The rates of major adverse cardiac events and cardiac death were similar in the R-ZES-treated group compared with the PES-treated group. © The Author(s) 2015.

  8. Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable-Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularization: 2-Year Results of the BIOSCIENCE Trial.

    PubMed

    Zbinden, Rainer; Piccolo, Raffaele; Heg, Dik; Roffi, Marco; Kurz, David J; Muller, Olivier; Vuilliomenet, André; Cook, Stéphane; Weilenmann, Daniel; Kaiser, Christoph; Jamshidi, Peiman; Franzone, Anna; Eberli, Franz; Jüni, Peter; Windecker, Stephan; Pilgrim, Thomas

    2016-03-15

    No data are available on the long-term performance of ultrathin strut biodegradable polymer sirolimus-eluting stents (BP-SES). We reported 2-year clinical outcomes of the BIOSCIENCE (Ultrathin Strut Biodegradable Polymer Sirolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent for Percutaneous Coronary Revascularisation) trial, which compared BP-SES with durable-polymer everolimus-eluting stents (DP-EES) in patients undergoing percutaneous coronary intervention. A total of 2119 patients with minimal exclusion criteria were assigned to treatment with BP-SES (n=1063) or DP-EES (n=1056). Follow-up at 2 years was available for 2048 patients (97%). The primary end point was target-lesion failure, a composite of cardiac death, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization. At 2 years, target-lesion failure occurred in 107 patients (10.5%) in the BP-SES arm and 107 patients (10.4%) in the DP-EES arm (risk ratio [RR] 1.00, 95% CI 0.77-1.31, P=0.979). There were no significant differences between BP-SES and DP-EES with respect to cardiac death (RR 1.01, 95% CI 0.62-1.63, P=0.984), target-vessel myocardial infarction (RR 0.91, 95% CI 0.60-1.39, P=0.669), target-lesion revascularization (RR 1.17, 95% CI 0.81-1.71, P=0.403), and definite stent thrombosis (RR 1.38, 95% CI 0.56-3.44, P=0.485). There were 2 cases (0.2%) of definite very late stent thrombosis in the BP-SES arm and 4 cases (0.4%) in the DP-EES arm (P=0.423). In the prespecified subgroup of patients with ST-segment elevation myocardial infarction, BP-SES was associated with a lower risk of target-lesion failure compared with DP-EES (RR 0.48, 95% CI 0.23-0.99, P=0.043, Pinteraction=0.026). Comparable safety and efficacy profiles of BP-SES and DP-EES were maintained throughout 2 years of follow-up. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443104. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by

  9. Paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction.

    PubMed

    Stone, Gregg W; Lansky, Alexandra J; Pocock, Stuart J; Gersh, Bernard J; Dangas, George; Wong, S Chiu; Witzenbichler, Bernhard; Guagliumi, Giulio; Peruga, Jan Z; Brodie, Bruce R; Dudek, Dariusz; Möckel, Martin; Ochala, Andrzej; Kellock, Alison; Parise, Helen; Mehran, Roxana

    2009-05-07

    There is no consensus regarding the safety and efficacy of drug-eluting stents, as compared with bare-metal stents, in patients with ST-segment elevation myocardial infarction who are undergoing primary percutaneous coronary intervention (PCI). We randomly assigned, in a 3:1 ratio, 3006 patients presenting with ST-segment elevation myocardial infarction to receive paclitaxel-eluting stents (2257 patients) or otherwise identical bare-metal stents (749 patients). The two primary end points of the study were the 12-month rates of target-lesion revascularization for ischemia (analysis powered for superiority) and a composite safety outcome measure of death, reinfarction, stroke, or stent thrombosis (powered for noninferiority with a 3.0% margin). The major secondary end point was angiographic evidence of restenosis at 13 months. Patients who received paclitaxel-eluting stents, as compared with those who received bare-metal stents, had significantly lower 12-month rates of ischemia-driven target-lesion revascularization (4.5% vs. 7.5%; hazard ratio, 0.59; 95% confidence interval [CI], 0.43 to 0.83; P=0.002) and target-vessel revascularization (5.8% vs. 8.7%; hazard ratio, 0.65; 95% CI, 0.48 to 0.89; P=0.006), with noninferior rates of the composite safety end point (8.1% vs. 8.0%; hazard ratio, 1.02; 95% CI, 0.76 to 1.36; absolute difference, 0.1 percentage point; 95% CI, -2.1 to 2.4; P=0.01 for noninferiority; P=0.92 for superiority). Patients treated with paclitaxel-eluting stents and those treated with bare-metal stents had similar 12-month rates of death (3.5% and 3.5%, respectively; P=0.98) and stent thrombosis (3.2% and 3.4%, respectively; P=0.77). The 13-month rate of binary restenosis was significantly lower with paclitaxel-eluting stents than with bare-metal stents (10.0% vs. 22.9%; hazard ratio, 0.44; 95% CI, 0.33 to 0.57; P<0.001). In patients with ST-segment elevation myocardial infarction who were undergoing primary PCI, implantation of paclitaxel-eluting

  10. The real world experience of the biodegradable polymer-coated sirolimus-eluting coronary stent system: Results From an "All-Comers" Clinical Experience.

    PubMed

    Rajasekhar, D; Vanajakshamma, V; Shashank, C; Srinivasakumar, M L; Sivasankara, C

    2016-09-01

    This INDOLIMUS Registry sought to evaluate the safety and efficacy of the biodegradable polymer coated Indolimus(®) sirolimus-eluting coronary stent for the treatment of coronary artery disease across a wide range of patients treated in routine clinical practice, including those with high-risk characteristics and complex lesions. First-generation drug-eluting stents utilize nonbiodegradable polymeric coatings, whose persistent presence in the arterial wall may negatively affect long-term outcomes. It has been hypothesized that persistent presence of polymer may compromise the safety of drug-eluting stents, and that therefore biodegradable polymer coatings might reduce late adverse events in an unselected patient population. All 530 consecutive unselected patients (415 males and 115 females) included who underwent percutaneous coronary intervention at the Sri Venkateswara Institute of Medical Sciences, Tirupati, India between August 2012 and March 2013, with an in-hospital, at 30-days and at 6-months follow-up. Retrospective analysis of those data had been done. A total of 617 lesions were treated in 530 enrolled patients (mean age 54.9 ± 10.8 years) with average stent length of 18.8 ± 6.0 mm. An average of 1.18 stents was implanted per patient. The patients' characteristics are noted as having 169 (31.9%) patients of diabetics and 215 (40.6%) hypertension. Smoking, alcoholism and tobacco chewing were found in 273 (51.5%), 130 (24.5%) and 17 (3.2%), respectively. The indications for intervention were unstable angina in 77 (14.5%) and previous myocardial infarction in 56 (10.6%) of the patients. Lesions were of type B2 in 264 (42.7%) and type C in 127 (20.6%). Stent delivery was successful in all cases and in-hospital, 30-days and 6-months follow-up of all 530 patients was obtained. The incidence of any major adverse cardiac events at in-hospital, at 30-days and at 6-months were 5 (0.94%), 8 (1.52%), and 18 (3.40%), respectively. Long term follow-up of

  11. Method for the analysis of triadimefon and ethofumesate from dislodgeable foliar residues on turfgrass by solid-phase extraction and in-vial elution.

    PubMed

    Runes, H B; Jenkins, J J; Field, J A

    1999-08-01

    Triadimefon, a fungicide, and ethofumesate, an herbicide, are commonly applied to turfgrass in the Pacific Northwest, resulting in foliar residues. A simple and rapid method was developed to determine triadimefon and ethofumesate concentrations from dislodgeable foliar residues on turfgrass. Turfgrass samples were washed, and wash water containing surfactant (a 0.126% solution) was collected for residue analysis. This analytical method utilizes a 25 mm C(8) Empore disk and in-vial elution to quantitatively determine triadimefon and ethofumesate in 170 mL aqueous samples. The analytes were eluted by placing the disk in a 2 mL autosampler vial with 980 microL of ethyl acetate and 20 microL of 2-chlorolepidine, the internal standard, for analysis by GC/MS. The method quantitation limits are 0.29 microg/L for ethofumesate and 0.59 microg/L for triadimefon. The method detection limits are 0.047 microg/L and 0.29 microg/L for ethofumesate and triadimefon, respectively. Concentrations of triadimefon and ethofumesate from dislodgeable foliar residues from a field study are reported.

  12. Medication eluting devices for the field of OBGYN (MEDOBGYN): 3D printed biodegradable hormone eluting constructs, a proof of concept study.

    PubMed

    Tappa, Karthik; Jammalamadaka, Udayabhanu; Ballard, David H; Bruno, Todd; Israel, Marissa R; Vemula, Harika; Meacham, J Mark; Mills, David K; Woodard, Pamela K; Weisman, Jeffery A

    2017-01-01

    3D printing has the potential to deliver personalized implants and devices for obstetric and gynecologic applications. The aim of this study is to engineer customizable and biodegradable 3D printed implant materials that can elute estrogen and/or progesterone. All 3D constructs were printed using polycaprolactone (PCL) biodegradable polymer laden with estrogen or progesterone and were subjected to hormone-release profile studies using ELISA kits. Material thermal properties were tested using thermogravimetric analysis and differential scanning calorimetry. The 3D printed constructs showed extended hormonal release over a one week period. Cytocompatibility and bioactivity were assessed using a luciferase assay. The hormone-laden 3D printed constructs demonstrated an increase in luciferase activity and without any deleterious effects. Thermal properties of the PCL and hormones showed degradation temperatures above that of the temperature used in the additive manufacturing process-suggesting that 3D printing can be achieved below the degradation temperatures of the hormones. Sample constructs in the shape of surgical meshes, subdermal rods, intrauterine devices and pessaries were designed and printed. 3D printing of estrogen and progesterone-eluting constructs was feasible in this proof of concept study. These custom designs have the potential to act as a form of personalized medicine for drug delivery and optimized fit based on patient-specific anatomy.

  13. Biodegradable-polymer drug-eluting stents vs. bare metal stents vs. durable-polymer drug-eluting stents: a systematic review and Bayesian approach network meta-analysis.

    PubMed

    Kang, Si-Hyuck; Park, Kyung Woo; Kang, Do-Yoon; Lim, Woo-Hyun; Park, Kyung Taek; Han, Jung-Kyu; Kang, Hyun-Jae; Koo, Bon-Kwon; Oh, Byung-Hee; Park, Young-Bae; Kandzari, David E; Cohen, David J; Hwang, Seung-Sik; Kim, Hyo-Soo

    2014-05-01

    The aim of this study was to compare the safety and efficacy of biodegradable-polymer (BP) drug-eluting stents (DES), bare metal stents (BMS), and durable-polymer DES in patients undergoing coronary revascularization, we performed a systematic review and network meta-analysis using a Bayesian framework. Study stents included BMS, paclitaxel-eluting (PES), sirolimus-eluting (SES), endeavor zotarolimus-eluting (ZES-E), cobalt-chromium everolimus-eluting (CoCr-EES), platinium-chromium everolimus-eluting (PtCr-EES), resolute zotarolimus-eluting (ZES-R), and BP biolimus-eluting stents (BP-BES). After a systematic electronic search, 113 trials with 90 584 patients were selected. The principal endpoint was definite or probable stent thrombosis (ST) defined according to the Academic Research Consortium within 1 year. Biodegradable polymer-biolimus-eluting stents [OR, 0.56; 95% credible interval (CrI), 0.33-0.90], SES (OR, 0.53; 95% CrI, 0.38-0.73), CoCr-EES (OR, 0.34; 95% CrI, 0.23-0.52), and PtCr-EES (OR, 0.31; 95% CrI, 0.10-0.90) were all superior to BMS in terms of definite or probable ST within 1 year. Cobalt-chromium everolimus-eluting stents demonstrated the lowest risk of ST of all stents at all times after stent implantation. Biodegradable polymer-biolimus-eluting stents was associated with a higher risk of definite or probable ST than CoCr-EES (OR, 1.72; 95% CrI, 1.04-2.98). All DES reduced the need for repeat revascularization, and all but PES reduced the risk of myocardial infarction compared with BMS. All DESs but PES and ZES-E were superior to BMS in terms of ST within 1 year. Cobalt-chromium everolimus-eluting stents was safer than any DES even including BP-BES. Our results suggest that not only the biodegradability of polymer, but the optimal combination of stent alloy, design, strut thickness, polymer, and drug all combined determine the safety of DES.

  14. Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention (SORT OUT V): a randomised non-inferiority trial.

    PubMed

    Christiansen, Evald Høj; Jensen, Lisette Okkels; Thayssen, Per; Tilsted, Hans-Henrik; Krusell, Lars Romer; Hansen, Knud Nørregaard; Kaltoft, Anne; Maeng, Michael; Kristensen, Steen Dalby; Bøtker, Hans Erik; Terkelsen, Christian Juhl; Villadsen, Anton Boel; Ravkilde, Jan; Aarøe, Jens; Madsen, Morten; Thuesen, Leif; Lassen, Jens Flensted

    2013-02-23

    Third-generation biodegradable polymer drug-eluting stents might reduce the risk of stent thrombosis compared with first-generation permanent polymer drug-eluting stents. We aimed to further investigate the effects of a biodegradable polymer biolimus-eluting stent compared with a durable polymer-coated sirolimus-eluting stent in a population-based setting. This randomised, multicentre, all-comer, non-inferiority trial was undertaken at three sites across western Denmark. Eligible patients were aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes, and at least one coronary artery lesion (>50% diameter stenosis). We randomly assigned patients (1:1) using an independently managed computer-generated allocation sequence to receive either a biolimus-eluting biodegradable polymer stent (Nobori, Terumo, Tokyo, Japan) or a sirolimus-eluting permanent polymer stent (Cypher Select Plus, Cordis, Johnson & Johnson, Warren, NJ, USA). The primary endpoint was a composite of safety (cardiac death, myocardial infarction, definite stent thrombosis) and efficacy (target vessel revascularisation) at 9 months, analysed by intention to treat (non-inferiority margin of 0·02). This trial is registered with ClinicalTrials.gov, number NCT01254981. From July, 2009, to January, 2011, we assigned 1229 patients (1532 lesions) to receive the biolimus-eluting stent and 1239 (1555 lesions) to receive the sirolimus-eluting stent. One patient was lost to follow-up because of emigration. Intention-to-treat analysis showed that 50 (4·1%) patients who were assigned the biolimus-eluting stent and 39 (3·1%) who were assigned the sirolimus-eluting stent met the primary endpoint (risk difference 0·9% [upper limit of one-sided 95% CI 2·1%]; p(non-inferiority)=0·06). Significantly more patients in the biolimus-eluting stent group had definite stent thrombosis at 12 months than did those in the sirolimus-eluting stent group (9 [0·7%] vs 2 [0·2%], risk

  15. Third-generation zotarolimus-eluting and everolimus-eluting stents in all-comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single-blind, multicentre, non-inferiority trial.

    PubMed

    von Birgelen, Clemens; Sen, Hanim; Lam, Ming Kai; Danse, Peter W; Jessurun, Gillian A J; Hautvast, Raymond W M; van Houwelingen, Gert K; Schramm, Alexander R; Gin, R Melvyn Tjon Joe; Louwerenburg, Johannes W; de Man, Frits H A F; Stoel, Martin G; Löwik, Marije M; Linssen, Gerard C M; Saïd, Salah A M; Nienhuis, Mark B; Verhorst, Patrick M J; Basalus, Mounir W Z; Doggen, Carine J M; Tandjung, Kenneth

    2014-02-01

    Third-generation, permanent-polymer-based drug-eluting stents with novel, flexible designs might be more easily delivered than previous generations of stents in complex coronary lesions, but might be less longitudinally stable. We aimed to assess the safety and efficacy in all-comer patients of two third-generation stents that are often used clinically, but that have not yet been compared, and one of which has not previously been assessed in a randomised trial. In this investigator-initiated, single-blind, multicentre, randomised, two-arm, non-inferiority trial, patients aged 18 years and older who required a percutaneous coronary intervention with implantation of a drug-eluting stent were recruited from four study sites in the Netherlands. We randomly assigned patients by independently managed computer-generated allocation sequences in a 1:1 ratio to receive either cobalt-chromium-based zotarolimus-eluting stents (Resolute Integrity, Medtronic, Santa Rosa, CA, USA) or platinum-chromium-based everolimus-eluting stents (Promus Element, Boston Scientific, Natick, MA, USA). Patients and analysts were masked to the allocated stent, but treating clinicians were not. The primary endpoint of target-vessel failure was a composite of safety (cardiac death or target-vessel-related myocardial infarction) and efficacy (target-vessel revascularisation) at 12 months, analysed by intention to treat (with a non-inferiority margin of 3·6%). This trial is registered with ClinicalTrials.gov, number NCT01331707. Between Nov 25, 2010, and May 24, 2012, 1811 eligible all-comer patients, with 2371 target lesions, were enrolled in the study. 370 (20%) patients presented with ST-elevation myocardial infarction and 447 (25%) with non-ST-elevation myocardial infarction. 906 patients were assigned to receive zotarolimus-eluting stents and 905 to receive everolimus-eluting stents. Ease of stent delivery was shown by very low numbers of patients requiring treatment other than their assigned

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

  17. 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…

  18. 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

  19. 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.

  20. 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

  1. Leaching potential of phenylurea herbicides in a calcareous soil: comparison of column elution and batch studies.

    PubMed

    Langeron, Julie; Sayen, Stéphanie; Couderchet, Michel; Guillon, Emmanuel

    2014-04-01

    The transfer of eleven phenylurea herbicides through soil columns was investigated in laboratory conditions in order to determine leaching properties in a calcareous soil. Elution curves with distilled water were plotted after herbicide application on the soil column. Phenylurea retention by the soil indicating interactions with soil can be classified as follows: fenuron < fluometron ≤ isoproturon = monuron < metoxuron < monolinuron < metobromuron < chlorotoluron < linuron = diuron < chlorbromuron. The number and nature of halogen atoms on the phenyl ring had an important influence on leaching. Retention was higher for molecules with higher number of halogen, and it was also higher for bromine than chlorine. Column elution experiments were compared to batch experiments from which the distribution coefficients K d were determined. According to Kendall correlation coefficients, parameter m/m 0 max from column experiments was relatively well linked to K d. In case of phenylurea, a linear relationship between K d and m/m 0 max was established.

  2. 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

    2016-09-06

    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.

  3. Binding and elution strategy for improved performance of arginine affinity chromatography in supercoiled plasmid DNA purification.

    PubMed

    Sousa, F; Prazeres, D M F; Queiroz, J A

    2009-02-01

    New interesting strategies for plasmid DNA (pDNA) purification were designed, exploiting affinity interactions between amino acids and nucleic acids. The potential application of arginine-based chromatography to purify pDNA has been recently described in our work; however, to achieve higher efficiency and selectivity in arginine affinity chromatography, it is essential to characterize the behaviour of binding/elution of supercoiled (sc) isoforms. In this study, two different strategies based on increased sodium chloride (225-250 mm) or arginine (20-70 mm) stepwise gradients are described to purify sc isoforms. Thus, it was proved that well-defined binding/elution conditions are crucial to enhance the purification performance, resulting in an improvement of the final plasmids yields and transfection efficiency, as this could represent a significant impact on therapeutic applications of the purified sc isoform. Copyright (c) 2008 John Wiley & Sons, Ltd.

  4. Subacute Drug-Eluting Stent Thrombosis Caused by Stent Underexpansion: Evaluation by Optical Coherence Tomography

    PubMed Central

    Martín-Reyes, Roberto; Jiménez-Valero, Santiago; Navarro, Felipe; Moreno, Raúl

    2011-01-01

    We present the case report of a patient presenting with ST segment elevation myocardial infarction due to a subacute drug-eluting stent trombosis within the proximal segment of the left circumflex artery (LCX). Six days before a total chronic occlusion was treated at the mid segment of the LCX by overlapping two drug-eluting stents. Optical coherence tomography (OCT) was helpful to demonstrate stent underexpansion of the overlaping segment as the main mechanism of early stent thrombosis. This case is illustrative about the potential role of OCT to identify the mechanisms of ST and thus guiding the PCI procedure. Moreover, our case shows the capability of the Imagewire to cross a severe stenosis due to stent underexpansion that could not be crossed by the IVUS catheter. PMID:21423540

  5. Acoustophoretic microfluidic chip for sequential elution of surface bound molecules from beads or cells

    PubMed Central

    Augustsson, Per; Malm, Johan; Ekström, Simon

    2012-01-01

    An acoustophoresis-based microfluidic flow-chip is presented as a novel platform to facilitate analysis of proteins and peptides loosely bound to the surface of beads or cells. The chip allows for direct removal of the background surrounding the beads or cells, followed by sequential treatment and collection of a sequence of up to five different buffer conditions. During this treatment, the beads/cells are retained in a single flow by acoustic radiation force. Eluted peptides are collected from the outlets and subsequently purified by miniaturized solid-phase extraction and analyzed with matrix assisted laser desorption mass spectrometry. Fundamental parameters such as the system fluidics and dispersion are presented. The device was successfully applied for wash and sequential elution of peptides bound to the surface of microbeads and human spermatozoa, respectively. PMID:24003343

  6. Physiological significance of benzo(. cap alpha. )pyrene adsorbed to carbon blacks: elution studies, AHH determinations

    SciTech Connect

    Buddingh, F.; Bailey, M.J.; Wells, B.; Haesemeyer, J.

    1981-07-01

    Desorption of benzo(..cap alpha..)pyrene from commercial carbon blacks by tissue fluids in vitro is compared to arylhydrocarbon hydroxylase induction in mice at three levels of carbon black exposure. Less than 0.005% of the adsorbed benzo(..cap alpha..)pyrene content determined by soxhlet extraction in toluene is eluted by human plasma, swine serum, swine lung homogenate and swine lung washings. Statistically significant differences in elution efficiency are observed for the various tissue fluids and carbon blacks. There is no detectable increase in AHH level in mouse lung or liver tissues even at the highest carbon black exposure and consumption rate of 1g/g bdywt/year.

  7. A current problem in cardiology: very late thrombosis after implantation of sirolimus eluting stent.

    PubMed

    Sharifkazemi, Mohammad Bagher; Zamirian, Mahmood; Aslani, Amir

    2007-01-01

    Discontinuation of antiplatelet medications has been strongly associated with coronary stent thrombosis. The first reported cases have been documented at 6 h to 6 weeks after stent implantation. This article presents a case of very late stent thrombosis 24 months after sirolimus eluting stent implantation and 18 months after clopidogrel discontinuation, despite aspirin continuation, and argues in favor of prolonging dual antiplatelet medication including clopidogrel in this setting, at least until data from randomized trials address this important issue.

  8. Elution characteristics of residual monomers in different light- and auto-curing resins.

    PubMed

    Danesh, Gholamreza; Hellak, Tobias; Reinhardt, Klaus-Jürgen; Végh, András; Schäfer, Edgar; Lippold, Carsten

    2012-11-01

    The aim of this in vitro study was to assess different auto-curing resins based on methylmethacrylate (MMA) and new light-curing resins based on urethane dimethacrylate (UDMA) regarding the residual monomers remaining in the resin and their elution over time. Specimens from three auto-curing and three light-curing resins were produced following the manufacturer's instructions. The concentration of residual MMA and UDMA monomers present in the resins as well as the quantity of the residual monomers released into artificial saliva solution after immersion times of 1, 3, and 7 days were analyzed by high-performance liquid chromatography (HPLC). Data were statistically analyzed using ANOVA and the post hoc Student-Newman-Keuls test. The highest and lowest amounts of residual monomers were found in the group of light-curing resins (p<0.05). The light-curing resins Triad Trans Sheet (0.06 wt%) and Primosplint (0.06 wt%) released over the entire immersion time of 7 days the smallest (p<0.05) quantity of UDMA. These two light-curing resins based on UDMA exhibited lower elution of residual monomers than auto-curing resins (MMA). The elution characteristics of the residual monomers do not seem to correlate with the residual monomer concentration in resins. These observations demonstrate that the quantitative determination of residual monomers alone - as required by the ISO specification 20795-1 - does not seem to be sufficient for an assessment of the biological properties of different resins. Instead, the evaluation of elution characteristics appears to be of higher clinical relevance.

  9. 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.

  10. 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.

  11. The influence of atherosclerotic plaques on the pharmacokinetics of a drug eluted from bioabsorbable stents.

    PubMed

    Ferreira, José A; Gonçalves, Lino; Naghipoor, Jahed; de Oliveira, Paula; Rabczuk, Timon

    2017-01-01

    In this paper the effect of plaque composition, on the accumulation of drug released by a drug eluting stent, is analyzed. The mathematical model is represented by two coupled systems of partial differential equations that describe the pharmacokinetics of drug in the stent coating and in the arterial wall. The influence of the stiffness and porosity of soft and hard plaques is studied. A case study based on optical coherence tomography images is also included. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Long-Term Clinical Outcomes of a Biodegradable Polymer-Based Biolimus-Eluting Stent.

    PubMed

    Im, Eui; Kim, Gwang-Sil; Shin, Dong-Ho; Kim, Jung-Sun; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2016-04-01

    To investigate the long-term clinical outcomes of biolimus-eluting stents with biodegradable polymers in real-world clinical practice. Long-term clinical outcomes of biolimus-eluting stents have not been clearly established. A total of 824 all-comer patients (971 lesions) treated with unrestricted implantation of a biolimus-eluting stent with a biodegradable polymer were prospectively enrolled. Patients were divided into complex (413 patients) versus noncomplex (411 patients) groups according to the complexity of coronary lesions. Long-term clinical outcomes for stent efficacy (target lesion revascularization) and safety (composite of cardiac death, target lesion-related myocardial infarction, and definite or probable stent thrombosis) were compared between the two groups during 5 years of follow-up. The complex group showed higher rates of decreased left ventricular ejection fraction, impaired renal function, previous history of myocardial infarction, and diabetes mellitus compared to the noncomplex group. In the overall population, the 5-year cumulative rate of target lesion revascularization was 4.8% (8.3% in the complex group vs 1.6% in the noncomplex group, P < 0.001). For stent safety, the 5-year cumulative rate for a composite of cardiac death, target lesion-related myocardial infarction, and stent thrombosis was 2.5% overall (3.9% in the complex group vs 1.1% in the noncomplex group, P = 0.010). Overall 5-year cumulative rate of stent thrombosis was 0.4% (0.5% in the complex vs 0.2% in the noncomplex group, P = 0.561) with no very late stent thrombosis (VLST). Biodegradable polymer-based biolimus-eluting stents showed favorable efficacy and safety in all-comer patients during 5 years of follow-up. © 2016, Wiley Periodicals, Inc.

  13. In vitro and in vivo performance of a dual drug-eluting stent (DDES).

    PubMed

    Huang, Yingying; Venkatraman, Subbu S; Boey, Freddy Y C; Lahti, Eeva M; Umashankar, P R; Mohanty, Mira; Arumugam, Sabareeswaran; Khanolkar, Laxmikant; Vaishnav, Sudhir

    2010-05-01

    This study reports on a dual drug-eluting stent (DDES) that has an anti-proliferative and an anti-thrombotic in a biodegradable polymer-coated onto a cobalt-chromium stent. The DDES was prepared by spray coating the bare metal stent with a biodegradable polymer loaded with sirolimus and triflusal, to treat against restenosis and thrombosis, respectively. The 2-layered dual-drug coated stent was characterized in vitro for surface properties before and after expansion, as well as for possible delamination by cross-sectioning the stent in vitro. The in vitro anti-platelet behavior of the triflusal-loaded films was investigated by using dynamic platelet adhesion measurements. Additionally, the in vitro degradation and release study of the films and the stents w/single sirolimus and dual sirolimus-triflusal in different formulations were examined. Finally, in vivo studies (in a porcine carotid artery model) were performed for acute thrombosis, inflammation and restenosis at 30 days. The in vitro results show DDES can sustain release both anti-proliferation drug (sirolimus) and anti-thrombosis drug (triflusal), two drugs were controlled in different rates to effectively reduce thrombosis and proliferation at the same time. In vivo results show a significant reduction in restenosis with dual-drug eluting stent compared with the controls (a bare metal stent, a sirolimus coated and a pure polymer-coated stent). The reduction in restenosis with a dual sirolimus-triflusal eluting stent is associated with an inhibition of inflammation, especially thrombus formation, suggesting that such dual-drug eluting stents have a role to play for the treatment of coronary artery disease.

  14. 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.

  15. 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).

  16. Drug-eluting stents versus bare-metal stents for acute coronary syndrome.

    PubMed

    Feinberg, Joshua; Nielsen, Emil Eik; Greenhalgh, Janette; Hounsome, Juliet; Sethi, Naqash J; Safi, Sanam; Gluud, Christian; Jakobsen, Janus C

    2017-08-23

    Approximately 3.7 million people died from acute coronary syndrome worldwide in 2012. Acute coronary syndrome, also known as myocardial infarction or unstable angina pectoris, is caused by a sudden blockage of the blood supplied to the heart muscle. Percutaneous coronary intervention is often used for acute coronary syndrome, but previous systematic reviews on the effects of drug-eluting stents compared with bare-metal stents have shown conflicting results with regard to myocardial infarction; have not fully taken account of the risk of random and systematic errors; and have not included all relevant randomised clinical trials. To assess the benefits and harms of drug-eluting stents versus bare-metal stents in people with acute coronary syndrome. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, SCI-EXPANDED, and BIOSIS from their inception to January 2017. We also searched two clinical trials registers, the European Medicines Agency and the US Food and Drug Administration databases, and pharmaceutical company websites. In addition, we searched the reference lists of review articles and relevant trials. Randomised clinical trials assessing the effects of drug-eluting stents versus bare-metal stents for acute coronary syndrome. We included trials irrespective of publication type, status, date, or language. We followed our published protocol and the methodological recommendations of Cochrane. Two review authors independently extracted data. We assessed the risks of systematic error by bias domains. We conducted Trial Sequential Analyses to control the risks of random errors. Our primary outcomes were all-cause mortality, major cardiovascular events, serious adverse events, and quality of life. Our secondary outcomes were angina, cardiovascular mortality, and myocardial infarction. Our primary assessment time point was at maximum follow-up. We assessed the quality of the evidence by the GRADE approach. We included 25

  17. 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.

  18. 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.

  19. Purification of 3-phosphoglycerate kinase from diverse sources by affinity elution chromatography.

    PubMed Central

    Fifis, T; Scopes, R K

    1978-01-01

    1. Affinity elution chromatography was used to purify phosphoglycerate kinase from a variety of sources. The choice of buffer pH for the chromatography was made according to the relative electrophoretic mobility of the enzyme from the species concerned. 2. Outlines of the methods used to isolate the enzyme from over 20 sources are presented. The enzyme was purified from the muscle tissue of a variety of mammals, fish and birds, from liver of several animals, from yeast, Escherichia coli, and plant leaves. The more acidic varieties of the enzymes were purified by conventional gradient elution from ion-exchangers as affinity elution procedures were not applicable. 3. The structural and kinetic parameters investigated show that phosphoglycerate kinase is evolutionarily a highly conservative enzyme; there were few differences in properties regardless of source or function (glycolytic, gluconeogenic or photosynthetic). 4. A detailed comparison of the enzyme preparations purified from bovine muscle and bovine liver failed to detect any significant differences between them; the evidence indicates that they are genetically identical. PMID:367367

  20. Second- and third-generation drug-eluting coronary stents: progress and safety.

    PubMed

    Akin, I; Schneider, H; Ince, H; Kische, S; Rehders, T C; Chatterjee, T; Nienaber, C A

    2011-05-01

    Drug-eluting stents (DES) have revolutionized the treatment of coronary artery disease by reducing the rate of in-stent restenosis from 20-40% with bare-metal stent (BMS) to 6-8% with DES. However, with widespread use of DES, safety concerns have risen due to the observation of late stent thrombosis. With this in mind and better understanding of mechanism and pathophysiology of stent thrombosis, the technological platform, especially innovative anti-restenotic agents, polymeric coatings, and stent platforms, improved with newer DES. Two second-generation DES, the Endeavor zotarolimus-eluting stent (ZES) and the Xience-V everolimus-eluting stent (EES), have provided promising results in both randomized controlled trials (SPIRIT and ENDEAVOR) and registries (E-Five, COMPARE) compared with bare-metal stents (BMS) and first-generation DES. Newer third-generation stent technology, especially biodegradable polymers, polymer-free stents, and biodegradable stents on the basis of poly-L-lactide (PLLA) or magnesium, has been evaluated in preclinical and initial clinical trials. However, despite encouraging initial results, long-term data of large-scale randomized trials as well as registries comparing them to currently approved first- and second-generation DES are still lacking.

  1. 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.

  2. Novel elution strategy for monitoring DNA counter-migration in the presence of electroosmotic flow.

    PubMed

    Zabzdyr, Jennifer L; Lillard, Sheri J

    2004-06-25

    The migration behavior of native (i.e., unlabelled) DNA in the presence of electroosmotic flow (EOF) was investigated in bare fused-silica capillaries. Employing a novel elution strategy, the influence of EOF on the net mobility of DNA was assessed by collecting the DNA that migrated anodically (i.e., against EOF) and out of the capillary inlet. Various conditions of pH and buffer-zone continuity were employed to characterize this phenomenon. Tris acid (TA, pH 5.14) and Tris base (TB, pH 9.36) were used as buffers in continuous systems, in which the capillary and the inlet reservoir contain the same buffer, and discontinuous systems, in which the capillary contains either TA or TB, and the inlet reservoir contains water. DNA that was ejected into the inlet vial was subsequently analyzed by capillary electrophoresis-laser-induced fluorescence. Both phiX174/HaeIII DNA and the beta-actin product of single-cell reverse transcriptase-polymerase chain reaction were used as DNA samples in this study. The mechanism of elution was found to depend on bulk flow, in the case of continuous solutions. However, with the discontinuous system, a localized decrease in EOF generated in the capillary tip appeared to impact elution. These findings serve to introduce an alternative approach for characterizing the mobility of highly charged species.

  3. Elution relationships to model affinity chromatography using a general rate model.

    PubMed

    Sandoval, Gabriela; Andrews, Barbara A; Asenjo, Juan A

    2012-11-01

    Different mathematical models with different degrees of complexity have been proposed to model affinity chromatography. In this work, in particular, a general rate model has been studied that considers axial dispersion, external film mass transfer, intraparticle diffusion, and kinetic effects investigating the influence in the simulations of two different relationships between the properties of the mobile phase and the affinity of different proteins to the ligand bound to the matrix. Two systems were used: Blue Sepharose and Protein A. With Blue Sepharose, an increasing linear salt gradient was used, and with Protein A, a decreasing semi-linear pH gradient. The kinetic parameters obtained in each of the two elution (adsorption/desorption) relationships studied (a power law type and an exponential type) led to very good agreements between experimental and simulated elution curves of mixtures of proteins finding that for more symmetrical peaks, the preferred elution relationship should be the exponential one, in contrast to the more asymmetrical peaks which shapes are better simulated by the power law relationship. Copyright © 2012 John Wiley & Sons, Ltd.

  4. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Zotarolimus-eluting durable-polymer-coated stent versus a biolimus-eluting biodegradable-polymer-coated stent in unselected patients undergoing percutaneous coronary intervention (SORT OUT VI): a randomised non-inferiority trial.

    PubMed

    Raungaard, Bent; Jensen, Lisette Okkels; Tilsted, Hans-Henrik; Christiansen, Evald Høj; Maeng, Michael; Terkelsen, Christian Juhl; Krusell, Lars Romer; Kaltoft, Anne; Kristensen, Steen Dalby; Bøtker, Hans Erik; Thuesen, Leif; Aarøe, Jens; Jensen, Svend Eggert; Villadsen, Anton Boel; Thayssen, Per; Veien, Karsten Tange; Hansen, Knud Nørregaard; Junker, Anders; Madsen, Morten; Ravkilde, Jan; Lassen, Jens Flensted

    2015-04-18

    New-generation drug-eluting coronary stents have reduced the risk of coronary events, especially in patients with complex disease or lesions. To what extent different stent platforms, polymers, and antiproliferative drugs affect outcomes, however, is unclear. We investigated the safety and efficacy of a third-generation stent by comparing a highly biocompatible durable-polymer-coated zotarolimus-eluting stent with a biodegradable-polymer-coated biolimus-eluting stent. This open-label, randomised, multicentre, non-inferiority trial was done at three sites across western Denmark. All patients who presented with stable coronary artery disease or acute coronary syndromes and at least one coronary artery lesion (more than 50% stenosis) from March, 2011, to August, 2012, were assessed for eligibility. Patients were randomly assigned in a 1:1 ratio to receive either the durable-polymer zotarolimus-eluting stent or the biodegradable-polymer biolimus-eluting stent. The primary endpoint was a composite of safety (cardiac death and myocardial infarction not clearly attributable to a non-target lesion) and efficacy (target-lesion revascularisation) at 12 months, analysed by intention to treat. The trial was powered to assess non-inferiority of durable-polymer zotarolimus-eluting stent compared with the biodegradable-polymer biolimus-eluting stent with a predetermined non-inferiority margin of 0·025. This trial is registered with ClinicalTrials.gov, number NCT01956448. Of 7103 screened, 1502 patients with 1883 lesions were assigned to receive the durable-polymer zotarolimus-eluting stent and 1497 patients with 1791 lesions to receive the biodegradable-polymer biolimus-eluting stent. 79 (5·3%) and 75 (5·0%) patients, respectively, met the primary endpoint (absolute risk difference 0·0025, upper limit of one-sided 95% CI 0·016%; p=0·004). The individual components of the primary endpoint did not differ significantly between stent types at 12 months. The durable

  6. Randomized Comparison of Ridaforolimus-Eluting and Zotarolimus-Eluting Coronary Stents in Patients with Coronary Artery Disease: Primary Results from the BIONICS Trial.

    PubMed

    Kandzari, David E; Smits, Pieter C; Love, Michael P; Ben-Yehuda, Ori; Banai, Shmuel; Robinson, Simon D; Jonas, Michael; Kornowski, Ran; Bagur, Rodrigo; Iniguez, Andres; Danenberg, Haim D; Feldman, Robert L; Jauhar, Rajiv; Chandna, Harish; Parikh, Manish A; Perlman, Gidon Y; Balcells, Mercedes; Markham, Peter M; Ozan, Melek Ozgu; Genereux, Philippe; Edelman, Elazer; Leon, Martin B; Stone, Gregg W

    2017-08-09

    Background -The safety and efficacy of a novel cobalt alloy-based coronary stent with a durable elastomeric polymer eluting the antiproliferative agent ridaforolimus for treatment of patients with coronary artery disease is undetermined. Methods -A prospective, international 1:1 randomized trial was conducted to evaluate in a noninferiority design the relative safety and efficacy of ridaforolimus-eluting stents (RES) and slow-release zotarolimus-eluting stents (ZES) among 1,919 patients at 76 centers undergoing percutaneous coronary intervention. Inclusion criteria allowed enrollment of patients with recent myocardial infarction (MI), total occlusions, bifurcations lesions and other complex conditions. Results -Baseline clinical and angiographic characteristics were similar between the groups. Overall, mean age was 63.4 years, 32.5% were diabetic and 39.7% presented with acute coronary syndromes. At 12 months, the primary endpoint of target lesion failure (composite of cardiac death, target vessel-related MI and target lesion revascularization) was 5.4% for both devices (upper bound of one-sided 95% confidence interval 1.8%, Pnoninferiority=0.001). Definite/probable stent thrombosis rates were low in both groups (0.4% RES vs. 0.6% ZES, P=0.75). 13-month angiographic in-stent late lumen loss was 0.22 ± 0.41 mm and 0.23 ± 0.39 mm (Pnoninferiority=0.004) for the RES and ZES groups, respectively, and intravascular ultrasound percent neointimal hyperplasia was 8.10 ± 5.81 and 8.85 ± 7.77, respectively (Pnoninferiority=0.01). Conclusions -In the present trial which allowed broad inclusion criteria, the novel RES met the prespecified criteria for noninferiority compared with ZES for the primary endpoint of target lesion failure at 12 months, and had similar measures of late lumen loss. These findings support the safety and efficacy of RES in patients representative of clinical practice. Clinical Trial Registration -URL: www.ClinicalTrials.gov Unique Identifier: NCT

  7. Meta-Analysis of Randomized Clinical Trials Comparing Biodegradable Polymer Drug-Eluting Stent to Second-Generation Durable Polymer Drug-Eluting Stents.

    PubMed

    El-Hayek, Georges; Bangalore, Sripal; Casso Dominguez, Abel; Devireddy, Chandan; Jaber, Wissam; Kumar, Gautam; Mavromatis, Kreton; Tamis-Holland, Jacqueline; Samady, Habib

    2017-03-13

    The authors sought to perform a meta-analysis of randomized clinical trials (RCTs) comparing the safety and efficacy of biodegradable polymer drug-eluting stents (BP-DES) to second-generation durable polymer drug-eluting stents (DP-DES). Prior meta-analyses have established the superiority of BP-DES over bare-metal stents and first-generation DP-DES; however, their advantage compared with second-generation DP-DES remains controversial. The authors searched PubMed and Scopus databases for RCTs comparing BP-DES to the second-generation DP-DES. Outcomes included target vessel revascularization (TVR) as efficacy outcome and cardiac death, myocardial infarction (MI), and definite or probable stent thrombosis (ST) as safety outcomes. In addition, we performed landmark analysis for endpoints beyond 1 year of follow-up and a subgroup analysis based on the stent characteristics. The authors included 16 RCTs comprising 19,886 patients in the meta-analysis. At the longest available follow-up (mean duration 26 months), we observed no significant differences in TVR (p = 0.62), cardiac death (p = 0.46), MI (p = 0.98), or ST (risk ratio: 0.83, 95% confidence interval: 0.64 to 1.09; p = 0.19). Our landmark analysis showed that BP-DES were not associated with a reduction in the risk of very late ST (risk ratio: 0.87, 95% confidence interval: 0.49 to 1.53; p = 0.62). Similar outcomes were seen regardless of the eluting drug (biolimus vs. sirolimus), the stent platform (stainless steel vs. alloy), the kinetics of polymer degradation or drug release (<6 months vs. >6 months), the strut thickness of the BP-DES (thin <100 μm vs. thick >100 μm), or the DAPT duration (≥6 months vs. ≥12 months). BP-DES have similar safety and efficacy profiles to second-generation DP-DES. Published by Elsevier Inc.

  8. Correlates and outcomes of late and very late drug-eluting stent thrombosis: results from DESERT (International Drug-Eluting Stent Event Registry of Thrombosis).

    PubMed

    Waksman, Ron; Kirtane, Ajay J; Torguson, Rebecca; Cohen, David J; Ryan, Thomas; Räber, Lorenz; Applegate, Robert; Waxman, Sergio; Gordon, Paul; Kaneshige, Kimberly; Leon, Martin B

    2014-10-01

    The aim of this study was to identify clinical, procedural, and angiographic correlates of late/very late drug-eluting stent (DES) thrombosis as well as to determine the clinical outcomes of these events. Late/very late DES thromboses are a poorly studied phenomenon, partly due to the relative infrequency of these events, even in large cohort studies. In the DESERT (International Drug-Eluting Stent Event Registry of Thrombosis), a retrospective, case-control registry, 492 cases of late/very late definite DES thrombosis from 21 international sites were matched in a 1:1 fashion with controls without stent thrombosis (ST). Controls were matched according to 2 criteria: same enrolling institution and date of initial DES implantation. Baseline and procedural variables were collected, and clinical follow-up was obtained for patients with ST as long as 1 year after the event. Offline quantitative coronary angiography was performed for a subset of 378 case-control pairs. The majority of ST events occurred after 1 year (75%) and continued to occur for as long as 7.3 years. The clinical presentation of late/very late ST events was mainly myocardial infarction (66.7% ST-segment elevation myocardial infarction and 22.0% non-ST-segment elevation myocardial infarction); in-hospital mortality was 3.8%. A minority of patients (30%) with ST were receiving dual-antiplatelet therapy at the time of the event. Independent clinical correlates of late/very late ST were younger age, African-American race, current smoking, multivessel disease, longer stented length, overlapping stents, and percutaneous coronary intervention of vein graft lesions. Independent angiographic correlates for late/very late ST were lesions within the left anterior descending artery or a bypass graft, thrombus, and a larger residual diameter stenosis after the initial DES implantation. Despite the large sample of ST cases, all identified correlates of late/very late ST had weak associations with subsequent ST

  9. Drug-eluting stents in percutaneous coronary intervention: a benefit-risk assessment.

    PubMed

    Byrne, Robert A; Sarafoff, Nikolaus; Kastrati, Adnan; Schömig, Albert

    2009-01-01

    Drug-eluting stent (DES) therapy has represented a very significant milestone in the evolution of percutaneous coronary intervention (PCI) therapy. This review attempts to provide a balanced overview of the unprecedented wealth of data generated on this new technology, by examining the evidence bases for anti-restenotic efficacy, safety and cost effectiveness. The performance of a DES may be related to each of its three components: stent backbone; carrier polymer (to control drug-release kinetics); and active drug. In terms of anti-restenotic efficacy, the most appropriate parameters to examine are target lesion revascularization, angiographic restenosis and late luminal loss. The principal safety parameters are overall mortality, myocardial infarction (MI) and stent thrombosis. Anti-restenotic superiority of DES over bare metal stents (BMS) has been demonstrated across a spectrum of disease from straightforward 'vanilla lesions' through higher disease complexity in pivotal clinical trials to phase IV studies of efficacy in 'off-label' populations. The treatment effect of DES versus BMS is consistent in terms of a reduction in the need for repeat intervention of the order of 35-70%. Regarding differential efficacy of first-generation DES, a benefit may exist in favour of the Cypher (sirolimus-eluting) stent over Taxus (paclitaxel-eluting), particularly in high-risk lesion subsets. The second-generation approved devices are the Endeavor (zotarolimus-eluting) and Xience (everolimus-eluting) DES. While all four of these stents are permanent polymer-based, the current focus of development is towards DES platforms that are devoid of durable polymer, the presence of which has been implicated in late adverse events. In terms of safety concerns raised in relation to DES therapy, it is reasonable to conclude the following at 4- to 5-year post-stent implantation: (i) that there is no increased risk of death or MI with DES (neither is there a general signal of mortality

  10. Biodegradable Polymer Biolimus-Eluting Stents Versus Durable Polymer Everolimus-Eluting Stents in Patients With Coronary Artery Disease: Final 5-Year Report From the COMPARE II Trial (Abluminal Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent).

    PubMed

    Vlachojannis, Georgios J; Smits, Pieter C; Hofma, Sjoerd H; Togni, Mario; Vázquez, Nicolás; Valdés, Mariano; Voudris, Vassilis; Slagboom, Ton; Goy, Jean-Jaques; den Heijer, Peter; van der Ent, Martin

    2017-06-26

    This analysis investigates the 5-year outcomes of the biodegradable polymer biolimus-eluting stent (BP-BES) and durable polymer everolimus-eluting stent (DP-EES) in an all-comers population undergoing percutaneous coronary intervention. Recent 1- and 3-year results from randomized trials have indicated similar safety and efficacy outcomes of BP-BES and DP-EES. Whether benefits of the biodegradable polymer device arise over longer follow-up is unknown. Moreover, in-depth, prospective, long-term follow-up data on metallic drug-eluting stents with durable or biodegradable polymers are scarce. The COMPARE II trial (Abluminal Biodegradable Polymer Biolimus-Eluting Stent Versus Durable Polymer Everolimus-Eluting Stent) was a prospective, randomized, multicenter, all-comers trial in which 2,707 patients were randomly allocated (2:1) to BP-BES or DP-EES. The pre-specified endpoint at 5 years was major adverse cardiac events, a composite of cardiac death, nonfatal myocardial infarction, or target vessel revascularization. Five-year follow-up was available in 2,657 patients (98%). At 5 years, major adverse cardiac events occurred in 310 patients (17.3%) in the BP-BES group and 142 patients (15.6%) in the DP-EES group (p = 0.26). The rate of the combined safety endpoint all-cause death or myocardial infarction was 15.0% in the BP-BES group versus 14.8% in the DP-EES group (p = 0.90), whereas the efficacy measure target vessel revascularization was 10.6% versus 9.0% (p = 0.18), respectively. Interestingly, definite stent thrombosis rates did not differ between groups (1.5% for BP-BES vs. 0.9% for DP-EES; p = 0.17). The 5-year analysis comparing biodegradable polymer-coated BES and the durable polymer-coated EES confirms the initial early- and mid-term results regarding similar safety and efficacy outcomes in this all-comers percutaneous coronary intervention population. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights

  11. Drug eluting balloons for de novo coronary lesions – a systematic review and meta-analysis

    PubMed Central

    2013-01-01

    Background The role of drug-eluting balloons (DEB) is unclear. Increasing evidence has shown a benefit for the treatment of in-stent restenosis. Its effect on de novo coronary lesions is more controversial. Several smaller randomized trials found conflicting results. Methods This is a systematic review and meta-analysis of randomized controlled trials (RCT) evaluating the effect of local Paclitaxel delivery/drug eluting balloons (DEB) (+/− bare metal stent) compared to current standard therapy (stenting) to treat de novo coronary lesions. Data sources for RCT were identified through a literature search from 2005 through 28 December 2012. The main endpoints of interest were target lesion revascularization (TLR), major adverse cardiac events (MACE), binary in-segment restenosis, stent thrombosis (ST), myocardial infarction (MI), late lumen loss (LLL) and mortality. A random effects model was used to calculate the pooled relative risks (RR) with 95% confidence intervals. Results Eight studies (11 subgroups) and a total of 1,706 patients were included in this analysis. Follow-up duration ranged from 6 to 12 months. Overall, DEB showed similar results to the comparator treatment. The relative risk (RR) for MACE was 0.95 (0.64 to 1.39); P = 0.776, for mortality it was 0.79 (0.30 to 2.11), P = 0.644, for stent thrombosis it was 1.45 (0.42 to 5.01), P = 0.560, for MI it was 1.26 (0.49 to 3.21), P = 0.629, for TLR it was 1.09 (0.71 to 1.68); P = 0.700 and for binary in-stent restenosis it was 0.96 (0.48 to 1.93), P = 0.918. Compared to bare metal stents (BMS), DEB showed a lower LLL (− 0.26 mm (−0.51 to 0.01)) and a trend towards a lower MACE risk (RR 0.66 (0.43 to 1.02)). Conclusion Overall, drug-eluting balloons (+/− bare metal stent) are not superior to current standard therapies (BMS or drug eluting stent (DES)) in treating de novo coronary lesions. However, the performance of DEB seems to lie in between DES and BMS with a trend towards superiority over BMS

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

    PubMed

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

    2014-10-03

    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

  13. Elution of TEGDMA and BisGMA from a resin and a resin composite cured with halogen or plasma light.

    PubMed

    Munksgaard, E C; Peutzfeldt, A; Asmussen, E

    2000-08-01

    Plasma arc light units for curing resin composites have been introduced with the claim of relatively short curing times. The purpose of the present study was to measure and compare elution of monomers from an experimental BisGMA-TEGDMA resin and a commercial resin composite when cured with a halogen unit and when cured with a plasma arc unit. Specimens of the materials were immersed in methanol, and the amounts of monomers released with time were analyzed by HPLC. By use of Fick's laws of diffusion, the amount of eluted monomers from the specimen at infinity was estimated. The elution from resin specimens and from resin composite specimens cured with the plasma arc light unit was 7 and 4 times higher, respectively, compared to the elution from specimens cured with the halogen unit. It was concluded that the plasma arc light curing unit did not provide optimal cure when used as recommended by the manufacturer.

  14. Sequential elution of multiply and singly phosphorylated peptides with polar-copolymerized mixed-mode RP18/SCX material.

    PubMed

    Li, Xiuling; Guo, Zhimou; Sheng, Qianying; Xue, Xingya; Liang, Xinmiao

    2012-06-21

    Novel polar-copolymerized mixed-mode RP18/SCX material was developed for feasible phosphopeptide enrichment, in which multiply and singly phosphorylated peptides could be sequentially eluted and separated with high selectivity.

  15. Functional comparison between BuMA Supreme biodegradable polymer sirolimus-eluting and durable polymer zotarolimus-eluting coronary stents using Quantitative Flow Ratio: PIONEER QFR substudy.

    PubMed

    Asano, Taku; Katagiri, Yuki; Collet, Carlos; Tenekecioglu, Erhan; Miyazaki, Yosuke; Sotomi, Yohei; Amoroso, Giovanni; Aminian, Adel; Brugaletta, Salvatore; Vrolix, Mathias; Hernandez-Antolín, Rosana; van de Harst, Pim; Iñiguez, Andres; Janssens, Luc; Smits, Pieter; Wykrzykowska, Joanna J; Ribeiro, Vasco Gama; Periera, Helder; da Silva, Pedro Canas; Piek, Jan J; Reiber, Johan H C; von Birgelen, Clemens; Sabaté, Manel; Onuma, Yoshinobu; Serruys, Patrick W

    2017-10-10

    Quantitative Flow Ratio (QFR) based on 3-dimensional quantitative coronary angiography (3D-QCA) is a novel method to assess the physiological functionality after treatment with stents. The current study aimed to evaluate the difference in physiological functionality 9 months after implantation of a bioresorbable polymer-based sirolimus-eluting stent with an electrografting base layer (BuMA Supreme: B-SES) versus a durable polymer-based zotarolimus-eluting stent (Resolute: R-ZES). The current post-hoc analysis was performed in the PIONEER randomized trial (1:1 randomization to B-SES [83 patients/95 lesions] and R-ZES [87 patients/101 lesions]). QFR was measured in stented vessels in both arms at pre-procedural, post-procedural and 9-month angiography without pharmacologically induced hyperemia (contrast QFR). At 9 months, both the values of QFR distal to the stent (B-SES: 0.89±0.10 vs. 0.89±0.11, p=0.97) and the numbers of the vessels with QFR ≤0.8 were not significantly different between the two groups (11.0% vs. 12.8%, p=0.72), while the in-stent binary restenosis rate was also comparable (3.7% versus 3.5%, P=1.00). QFR gradient across the device (∆QFR) at 9 months was also similar between both groups (B-SES: 0.03±0.04 vs. 0.03±0.07, p=0.95). Quantitative flow assessment 9 months after stenting did not differ between B-SES and R-ZES, despite of a significant difference in in-stent late lumen loss.

  16. Efficacy and safety of biodegradable polymer biolimus-eluting stents versus durable polymer drug-eluting stents: a meta-analysis.

    PubMed

    Ye, Yicong; Xie, Hongzhi; Zeng, Yong; Zhao, Xiliang; Tian, Zhuang; Zhang, Shuyang

    2013-01-01

    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. 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. 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). 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. http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42013004364#.UnM2lfmsj6J.

  17. First-in-man randomized comparison of BuMA Supreme biodegradable polymer sirolimus-eluting versus durable polymer zotarolimus-eluting coronary stents: The PIONEER trial.

    PubMed

    von Birgelen, Clemens; Asano, Taku; Amoroso, Giovanni; Aminian, Adel; Brugaletta, Salvatore; Vrolix, Mathias; Hernandez-Antolín, Rosana; van de Harst, Pim; Iñiguez, Andres; Janssens, Luc; Smits, Pieter C; Wykrzykowska, Joanna J; Ribeiro, Vasco Gama; Periera, Helder; Canas da Silva, Pedro; Piek, Jan J; Onuma, Yoshinobu; Serruys, Patrick W; Sabaté, Manel

    2017-09-19

    A second iteration of a sirolimus-eluting stent (SES) that has a biodegradable PLGA-polymer coating with electrografting base layer on a thin-strut (80µm) cobalt-chromium platform (BuMA Supreme; SINOMED, Tianjin, China) has been developed. This first-in-man trial assessed the efficacy and safety of the novel device. This randomized, multi-center, single-blinded, non-inferiority trial compared BuMA Supreme SES versus contemporary durable polymer zotarolimus-eluting stents (ZES) in terms of angiographic in-stent late lumen loss (LLL) at 9-months follow-up as the primary endpoint. A total of 170 patients were randomly allocated to treatment with SES (n=83) or ZES (n=87). At 9-month angiographic follow-up, in-stent LLL was 0.29±0.33mm in SES and 0.14±0.37mm in ZES (Pnon-inferiority=0.45). The in-stent percent diameter stenosis and the binary restenosis rate of the two treatment arms were similar (19.2±12.0% vs. 16.1±12.6%, p=0.09, and 3.3% vs. 4.4%, P=1.00, respectively). At 12-month clinical follow-up, there was no difference between treatment arms with regard to a device-oriented composite clinical endpoint (4.9% vs. 5.7%; p=0.72). The PIONEER trial did not meet its primary endpoint in terms of in-stent LLL at 9-month follow-up. However, this result did not translate into any increase in restenosis rate or impairment in 12-month clinical outcomes.

  18. 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

  19. Randomized clinical trial comparing abluminal biodegradable polymer sirolimus-eluting stents with durable polymer sirolimus-eluting stents: Nine months angiographic and 5-year clinical outcomes.

    PubMed

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

    2016-09-01

    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. 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. 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). 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.

  20. Stent thrombosis with biodegradable polymer drug-eluting stents versus durable polymer sirolimus-eluting stents: an update meta-analysis.

    PubMed

    Zhu, Lin; Lv, Yi Ning; Wang, Li Yu

    2015-01-01

    Durable polymer sirolimus-eluting stents (DP-SES) are associated with a low risk of stent thrombosis; biodegradable polymer drug-eluting stents (BP-DES) were designed to reduce these risks. However, their benefits are still variable. We undertook a meta-analysis of randomized trials identified by systematic searches of Medline, Embase, and the Cochrane Database. Eleven studies (9,676 patients) with a mean follow-up of 22.6 months were included. Overall, compared with DP-SES, BP-DES significantly lowered the rate of definite or probable stent thrombosis (RR, 0.73; 95% CI, 0.55-0.97; p = 0.03; I(2) = 0.0%) due to a decreased risk of very late stent thrombosis (RR, 0.26; 95% CI, 0.11-0.63; p = 0.00; I(2) = 0.0%). However, BP-DES were associated with a comparable rate of early and late stent thrombosis. Meanwhile, BP-DES were associated with a broadly equivalent risk of target vessel revascularization (RR, 0.90; 95% CI, 0.78-1.03; p = 0.13; I(2) = 0.0%), cardiac death (RR, 0.89; 95% CI, 0.72-1.09; p = 0.24; I(2) = 0.0%), myocardial infarction (RR, 1.03; 95% CI, 0.84-1.26; p = 0.79; I(2) = 0.0%), and major adverse cardiac events (MACE; RR, 0.91; 95% CI, 0.83-1.0; p = 0.08; I(2) = 0.0%). Furthermore, angiographic data showed that in-stent and in-segment late luminal loss were similar between the two groups. Compared with DP-SES, BP-DES were associated with a lower rate of very late stent thrombosis and an equivalent risk of MACE. Larger randomized studies are needed to confirm this finding.

  1. Efficacy of drug-eluting stents for treating in-stent restenosis of drug-eluting stents (from the Korean DES ISR multicenter registry study [KISS]).

    PubMed

    Ko, Young-Guk; Kim, Jung-Sun; Kim, Byeong-Keuk; Choi, Donghoon; Hong, Myeong-Ki; Jeon, Dong Woon; Yang, Joo-Young; Ahn, Young Keun; Jeong, Myung Ho; Yu, Cheol Woong; Yun, Kyeong-Ho; Lim, Do-Sun; Jang, Yangsoo

    2012-03-01

    There is currently no established standard treatment for in-stent restenosis (ISR) after the implantation of a drug-eluting stent (DES). The aim of this study was to investigate the efficacy of DES versus balloon angioplasty (BA) for the treatment of DES ISR in a multicenter registry cohort. After matching propensity scores of 805 patients with DES ISR treated with either DES (n = 422) or BA (n = 383), 268 matched pairs were selected and analyzed for major adverse cardiac events, a composite of death, myocardial infarction, and target-vessel revascularization, as the primary end point. Baseline clinical and lesion characteristics of the matched pairs were similar. Survival free of major adverse cardiac events at 2 years was higher with DES compared to BA (88.9% vs 78.7%, p <0.001), mainly because of higher TVR-free survival (92.4% vs 81.0%, p <0.001). Among various baseline variables, BA (hazard ratio 2.546, 95% confidence interval 1.412 to 4.593, p = 0.002) was the most important independent risk factor for recurrent target vessel revascularization, followed by acute coronary syndromes as the clinical presentation of DES ISR, and previous implantation of a sirolimus-eluting stent. Survival free of death, myocardial infarction, or stent thrombosis did not differ between the 2 groups. Whereas there was no significant difference in survival free of target vessel revascularization between DES and BA for focal ISR lesions, DES was superior to BA in diffuse ISR lesions (94.3% vs 75.2% at 2 years, p <0.001). In conclusion, compared to BA, the implantation of DES was safe and more effective in the treatment of DES ISR.

  2. Long-term (three-year) safety and efficacy of everolimus-eluting stents compared to paclitaxel-eluting stents (from the SPIRIT III Trial).

    PubMed

    Applegate, Robert J; Yaqub, Manejeh; Hermiller, James B; Sood, Poornima; Yu, Shui; Doostzadeh, Julie; Williams, Jerome E; Farhat, Naim; Caputo, Ronald; Lansky, Alexandra J; Cutlip, Donald E; Sudhir, Krishnankutty; Stone, Gregg W

    2011-03-15

    The safety and efficacy of the XIENCE V everolimus-eluting stent (EES) compared to the Taxus Express(2) paclitaxel-eluting stent (PES) has been demonstrated through 2 years in the SPIRIT II and III randomized clinical trials, but limited longer-term data have been reported. In the SPIRIT III trial, 1,002 patients with up to 2 lesions in 2 coronary arteries were randomized 2:1 to EESs versus PESs at 65 United States sites. At completion of 3-year follow-up, treatment with EES compared to PES resulted in a significant 30% decrease in the primary clinical end point of target vessel failure (cardiac death, myocardial infarction, or ischemic-driven target vessel revascularization, 13.5% vs 19.2%, hazard ratio 0.70, 95% confidence interval 0.50 to 0.96, p = 0.03) and a 43% decrease in major adverse cardiovascular events, cardiac death, myocardial infarction, or ischemic-driven target lesion revascularization (9.1% vs 15.7%, hazard ratio 0.57, 95% confidence interval 0.39 to 0.83, p = 0.003). In a landmark analysis, major adverse cardiovascular events were decreased to a similar extent with EES compared to PES 0 through 1 year and 1 year through 3 years (hazard ratio 0.56, 95% confidence interval 0.35 to 0.90; hazard ratio 0.59, 95% confidence interval 0.31 to 1.11, respectively). In conclusion, patients treated with EES rather than PES in the SPIRIT III trial had significantly improved event-free survival at 3 years. From 1 year to 3 years hazard curves continued to diverge in favor of EES, consistent with an improving long-term safety and efficacy profile of EES compared to PES, with no evidence of late catchup.

  3. 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.

  4. A complete metal jacket case using ten paclitaxel-eluting stents for multiple de novo coronary artery lesions.

    PubMed

    Suh, Soon Yong; Rha, Seung-Woon; Choi, Cheol Ung; Kim, Jin Won; Kim, Eung Ju; Park, Chang Gyu; Seo, Hong Seog; Oh, Dong Joo

    2007-02-07

    Although full metal jacket using drug-eluting stent (DES) for a single coronary artery disease has sparsely been described before, there is no report of safety and efficacy of complete metal jacket from left main (LM) to three major coronary arteries. We report a complete metal jacket case using 10 paclitaxel-eluting stents (PES; Taxus, Boston Scientific) for a triple vessel diffuse de novo coronary diseases who refused coronary artery bypass graft.

  5. True and false reversal of the elution order of barbiturates on a bonded cellulose-based chiral stationary phase.

    PubMed

    Ghanem, Ashraf

    2006-11-03

    A set of racemic N-alkylated barbiturates were investigated for their direct enantioselective HPLC separation on a new chiral stationary phase (CSP) containing cellulose tris(3,5-dimethylphenylcarabamate) immobilized onto silica gel (Chiralpak IB) and its coated version (Chiralcel OD). They were online detected by UV and optical rotation detectors to trace the elution order of their enantiomers. Surprisingly, examples of false and true reversal of the elution order of enantiomers of barbiturates were observed and reported.

  6. Poly(N-vinyl-2-pyrrolidone) elution from polysulfone dialysis membranes by varying solvent and wall shear stress.

    PubMed

    Namekawa, Koki; Matsuda, Masato; Fukuda, Makoto; Kaneko, Ami; Sakai, Kiyotaka

    2012-06-01

    Some dialysis patients are treated with post-hemodiafiltration (HDF); the blood viscosity of the patients who undergo post-HDF is higher than that of the patients who undergo conventional hemodialysis. This study aims to evaluate poly(N-vinyl-2-pyrrolidone) (PVP) elution from PSf dialysis membranes by varying solvents and high wall shear stress caused by blood viscosity. We tested three commercial membranes: APS-15SA (Asahi Kasei Kuraray), CX-1.6U (Toray) and FX140 (Fresenius). Dialysate and blood sides of the dialyzers were primed with reverse osmosis (RO) water and saline. RO water, saline and dextran solution (2.9 and 5.8 mPa s) were circulated in the blood side. The amount of eluted PVP was determined by 0.02 N iodometry. The hardness and adsorption force of human serum albumin (HSA) on the membrane surfaces were measured by the atomic force microscope. When wall shear stress was increased using dextran, the amount of PVP eluted by the 2.9 mPa s solution equaled that eluted by the 5.8 mPa s solution with APS-15SA and CX-1.6U sterilized by gamma rays. The amount of PVP eluted by the 5.8 mPa s solution was higher than that eluted by the 2.9 mPa s solution with FX140 sterilized by autoclaving. The wall shear stress increased the PVP elution from the surface, hardness and adsorption force of HSA. Sufficient gamma-ray irradiation is effective in decreasing PVP elution.

  7. Elution and Mechanical Strength of Vancomycin-Loaded Bone Cement: In Vitro Study of the Influence of Brand Combination

    PubMed Central

    Tai, Ching-Lung; Chen, Szu-Yuan; Chang, Chih-Hsiang; Chang, Yu-Han; Hsieh, Pang-Hsin

    2016-01-01

    Antibiotic-loaded bone cement (ALBC) is widely used in orthopaedic surgery for both prevention and treatment of infection. Little is known about the effect of different brand combinations of antibiotic and bone cement on the elution profile and mechanical strength of ALBC. Standardized specimens that consisted of one of the 4 brands of bone cement and one of the 3 brands of vancomycin were fashioned, producing 12 combinations of ALBC. Two dosages of vancomycin in 40g bone cement were used to represent the high (4g vancomycin) and low (1g vancomycin) dose groups. Concentrations of vancomycin elution from ALBC was measured for up to 336 hours. The ultimate compression strength was tested at axial compression using a material testing machine before and after elution. In both high-dose and low-dose groups, Lyo-Vancin in PALACOS bone cement resulted in the highest cumulative elution and Vanco in Simplex P bone cement resulted in the lowest elution (458% and 65% higher in high- and low-dose groups, respectively). The mechanical strength was not significantly compromised in all groups with low dose vancomycin (range: 70.31 ± 2.74 MPa to 87.28 ± 8.26MPa after elution). However, with the addition of high dose vancomycin, there was a mixed amount of reduction in the ultimate compression strength after cement aging, ranging from 5% (Vanco in Simplex P, 81.10 ± 0.48 MPa after elution) to 38% (Sterile vancomycin in CMW, 60.94 ± 5.74 MPa after elution). We concluded that the selection of brands of vancomycin and bone cement has a great impact on the release efficacy and mechanical strength of ALBC. PMID:27855203

  8. Drug eluting and bare metal stents in people with and without diabetes: collaborative network meta-analysis

    PubMed Central

    Stettler, Christoph; Allemann, Sabin; Wandel, Simon; Kastrati, Adnan; Morice, Marie Claude; Schömig, Albert; Pfisterer, Matthias E; Stone, Gregg W; Leon, Martin B; de Lezo, José Suárez; Goy, Jean-Jacques; Park, Seung-Jung; Sabaté, Manel; Suttorp, Maarten J; Kelbaek, Henning; Spaulding, Christian; Menichelli, Maurizio; Vermeersch, Paul; Dirksen, Maurits T; Cervinka, Pavel; Carlo, Marco De; Erglis, Andrejs; Chechi, Tania; Ortolani, Paolo; Schalij, Martin J; Diem, Peter; Meier, Bernhard; Windecker, Stephan

    2008-01-01

    Objective To compare the effectiveness and safety of three types of stents (sirolimus eluting, paclitaxel eluting, and bare metal) in people with and without diabetes mellitus. Design Collaborative network meta-analysis. Data sources Electronic databases (Medline, Embase, the Cochrane Central Register of Controlled Trials), relevant websites, reference lists, conference abstracts, reviews, book chapters, and proceedings of advisory panels for the US Food and Drug Administration. Manufacturers and trialists provided additional data. Review methods Network meta-analysis with a mixed treatment comparison method to combine direct within trial comparisons between stents with indirect evidence from other trials while maintaining randomisation. Overall mortality was the primary safety end point, target lesion revascularisation the effectiveness end point. Results 35 trials in 3852 people with diabetes and 10 947 people without diabetes contributed to the analyses. Inconsistency of the network was substantial for overall mortality in people with diabetes and seemed to be related to the duration of dual antiplatelet therapy (P value for interaction 0.02). Restricting the analysis to trials with a duration of dual antiplatelet therapy of six months or more, inconsistency was reduced considerably and hazard ratios for overall mortality were near one for all comparisons in people with diabetes: sirolimus eluting stents compared with bare metal stents 0.88 (95% credibility interval 0.55 to 1.30), paclitaxel eluting stents compared with bare metal stents 0.91 (0.60 to 1.38), and sirolimus eluting stents compared with paclitaxel eluting stents 0.95 (0.63 to 1.43). In people without diabetes, hazard ratios were unaffected by the restriction. Both drug eluting stents were associated with a decrease in revascularisation rates compared with bare metal stents in people both with and without diabetes. Conclusion In trials that specified a duration of dual antiplatelet therapy of six

  9. 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.

  10. 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

  11. First- and second-generation drug-eluting balloons for femoro-popliteal arterial obstructions: update of technique and results.

    PubMed

    De Vries, J P P M; Karimi, A; Fioole, B; Van Leersum, M; Werson, D A B; Van Den Heuvel, D A F

    2013-06-01

    The use of drug-eluting balloons for treatment of long-segment femoropopliteal artery obstructions has become widespread in recent years. The possibility to deliver a drug into the arterial wall with sustained antiproliferative effects, without leaving behind metal scaffolding, seems very promising. The current generation of drug-eluting balloons differs in the formulation of the drug (usually paclitaxel), technique of coating, and the elution excipients. Results of published randomized trials are reviewed in this report. A new innovative coating technique has been introduced recently. The PRIMUS® coronary drug-eluting balloon and the Legflow® peripheral drug-eluting balloon consist of paclitaxel nanoparticles that are embedded underneath the surface of the balloon as well as inside a new shellolic acid drug-release matrix. Risk for dislodgement of the paclitaxel particles is minimized in the newest generation of drug-eluting balloons. Short-term in vitro and in vivo results of this stable, coated balloon are promising, and large randomized trials have been started recently to gather more long-term and robust clinical data.

  12. 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

    2015-07-03

    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.

  13. Solvent modulated linear pH gradient elution for the purification of conventional and bispecific antibodies: Modeling and application.

    PubMed

    Kluters, Simon; Hafner, Mathias; von Hirschheydt, Thomas; Frech, Christian

    2015-10-30

    Classical ion-exchange chromatography using a linear salt gradient to elute the adsorbed protein at fixed pH is the most common method to separate product-related impurities during downstream processing of biopharmaceuticals. Linear pH gradient elution provides a useful alternative by separating proteins in a linear pH gradient at fixed salt concentration. Although linear pH gradient elution provides excellent selectivity, it is rarely encountered in industrial purification processes. Here, a stoichiometric displacement model is used to characterize pH gradient elution based on simple linear gradient elution experiments. Protein retention behavior is described with respect to the pH dependencies of the characteristic binding charge and the equilibrium constant of the ion exchange reaction. Furthermore, the influence of solvent composition using PEG as a mobile phase modifier is investigated. Validity and applicability of the model are demonstrated for the purification of a conventional monoclonal antibody from soluble aggregates and for a novel bispecific antibody format containing a unique product-related impurity profile. pH step elution protocols are derived from model calculations without further optimization experiments necessary.

  14. A case of Z/E-isomers elution order inversion caused by cosolvent percentage change in supercritical fluid chromatography.

    PubMed

    Pokrovskiy, Oleg I; Ustinovich, Konstantin B; Usovich, Oleg I; Parenago, Olga O; Lunin, Valeriy V; Ovchinnikov, Denis V; Kosyakov, Dmitry S

    2017-01-06

    A case of elution order inversion caused by cosolvent percentage change in supercritical fluid chromatography was observed and investigated in some detail. Z- and E-isomers of phenylisobutylketone oxime experience an elution order reversal on most columns if the mobile phase consists of CO2 and alcohol. At lower percentages of alcohol Z-oxime is retained less, somewhere at 2-5% coelution occurs and at larger cosolvent volume elution order reverses - Z-oxime is eluted later than E-oxime. We suppose inversion with CO2-ROH phases happens due to a shift in balance between two main interactions governing retention. At low ROH percentages stationary phase surface is only slightly covered by ROH molecules so oximes primarily interact with adsorption sites via hydrogen bond formation. Due to intramolecular sterical hindrance Z-oxime is less able to form hydrogen bonds and consequently is eluted first. At higher percentages alcohols occupy most of strong hydrogen bonding sites on silica surface thus leaving non-specific electrostatic interactions predominantly responsible for Z/E selectivity. Z-oxime has a much larger dipole moment than E-oxime and at these conditions it is eluted later. Additional experimental data with CO2-CH3CN, hexane-iPrOH and CHF3-ROH mobile phases supporting this explanation are presented.

  15. Application of quality by design (QbD) approach to ultrasonic atomization spray coating of drug-eluting stents.

    PubMed

    McDermott, Martin; Chatterjee, Sharmista; Hu, Xiaoli; Ash-Shakoor, Ariel; Avery, Reginald; Belyaeva, Anastasiya; Cruz, Celia; Hughes, Minerva; Leadbetter, Joanne; Merkle, Conrad; Moot, Taylor; Parvinian, Sepideh; Patwardhan, Dinesh; Saylor, David; Tang, Nancy; Zhang, Tina

    2015-08-01

    The drug coating process for coated drug-eluting stents (DES) has been identified as a key source of inter- and intra-batch variability in drug elution rates. Quality-by-design (QbD) principles were applied to gain an understanding of the ultrasonic spray coating process of DES. Statistically based design of experiments (DOE) were used to understand the relationship between ultrasonic atomization spray coating parameters and dependent variables such as coating mass ratio, roughness, drug solid state composite microstructure, and elution kinetics. Defect-free DES coatings composed of 70% 85:15 poly(DL-lactide-co-glycolide) and 30% everolimus were fabricated with a constant coating mass. The drug elution profile was characterized by a mathematical model describing biphasic release kinetics. Model coefficients were analyzed as a DOE response. Changes in ultrasonic coating processing conditions resulted in substantial changes in roughness and elution kinetics. Based on the outcome from the DOE study, a design space was defined in terms of the critical coating process parameters resulting in optimum coating roughness and drug elution. This QbD methodology can be useful to enhance the quality of coated DES.

  16. Ultrathin strut biodegradable polymer sirolimus-eluting stent versus durable polymer everolimus-eluting stent for percutaneous coronary revascularisation (BIOSCIENCE): a randomised, single-blind, non-inferiority trial.

    PubMed

    Pilgrim, Thomas; Heg, Dik; Roffi, Marco; Tüller, David; Muller, Olivier; Vuilliomenet, André; Cook, Stéphane; Weilenmann, Daniel; Kaiser, Christoph; Jamshidi, Peiman; Fahrni, Therese; Moschovitis, Aris; Noble, Stéphane; Eberli, Franz R; Wenaweser, Peter; Jüni, Peter; Windecker, Stephan

    2014-12-13

    Refinements in stent design affecting strut thickness, surface polymer, and drug release have improved clinical outcomes of drug-eluting stents. We aimed to compare the safety and efficacy of a novel, ultrathin strut cobalt-chromium stent releasing sirolimus from a biodegradable polymer with a thin strut durable polymer everolimus-eluting stent. We did a randomised, single-blind, non-inferiority trial with minimum exclusion criteria at nine hospitals in Switzerland. We randomly assigned (1:1) patients aged 18 years or older with chronic stable coronary artery disease or acute coronary syndromes undergoing percutaneous coronary intervention to treatment with biodegradable polymer sirolimus-eluting stents or durable polymer everolimus-eluting stents. Randomisation was via a central web-based system and stratified by centre and presence of ST segment elevation myocardial infarction. Patients and outcome assessors were masked to treatment allocation, but treating physicians were not. The primary endpoint, target lesion failure, was a composite of cardiac death, target vessel myocardial infarction, and clinically-indicated target lesion revascularisation at 12 months. A margin of 3·5% was defined for non-inferiority of the biodegradable polymer sirolimus-eluting stent compared with the durable polymer everolimus-eluting stent. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT01443104. Between Feb 24, 2012, and May 22, 2013, we randomly assigned 2119 patients with 3139 lesions to treatment with sirolimus-eluting stents (1063 patients, 1594 lesions) or everolimus-eluting stents (1056 patients, 1545 lesions). 407 (19%) patients presented with ST-segment elevation myocardial infarction. Target lesion failure with biodegradable polymer sirolimus-eluting stents (69 cases; 6·5%) was non-inferior to durable polymer everolimus-eluting stents (70 cases; 6·6%) at 12 months (absolute risk difference -0·14%, upper limit of one

  17. A randomized optical coherence tomography study of coronary stent strut coverage and luminal protrusion with rapamycin-eluting stents.

    PubMed

    Moore, Philip; Barlis, Peter; Spiro, Jonathan; Ghimire, Gopal; Roughton, Michael; Di Mario, Carlo; Wallis, William; Ilsley, Charles; Mitchell, Andrew; Mason, Mark; Kharbanda, Rajesh; Vincent, Peter; Sherwin, Spencer; Dalby, Miles

    2009-05-01

    We used optical coherence tomography, which has a resolution of <20 microm, to analyze thin layers of neointima in rapamycin-eluting coronary stents. Lack of neointimal coverage has been implicated in the pathogenesis of drug-eluting coronary stent thrombosis. Angiography and intracoronary ultrasound lack the resolution to examine this. We conducted a randomized trial in patients receiving polymer-coated rapamycin-eluting stents (Cypher, Cordis, Johnson & Johnson, Miami, Florida) and nonpolymer rapamycin-eluting stents (Yukon, Translumina, Hechingen, Germany) to examine neointimal thickness, stent strut coverage, and protrusion at 90 days. Twenty-four patients (n = 12 for each group) underwent stent deployment and invasive follow-up at 90 days with optical coherence tomography. The primary end point was binary stent strut coverage. Coprimary end points were neointimal thickness and stent strut luminal protrusion. No patient had angiographic restenosis. For polymer-coated and nonpolymer rapamycin-eluting stents, respectively, mean (SD), neointimal thickness was 77.2 (25.6) microm versus 191.2 (86.7) mum (p < 0.001). Binary stent strut coverage was 88.3% (11.8) versus 97.2% (6.1) (p = 0.030). Binary stent strut protrusion was 26.5% (17.5) versus 4.8% (8.6) (p = 0.001). Mean neointimal thickness for the polymer-coated rapamycin-eluting stent was significantly less than the nonpolymer rapamycin-eluting stent but as a result coverage was not homogenous, with >10% of struts being uncovered. High-resolution imaging allowed development of the concept of the protrusion index, and >25% of struts protruded into the vessel lumen with the polymer-coated rapamycin-eluting stent compared with <5% with the nonpolymer rapamycin-eluting stent. These findings may have important implications for the risk of stent thrombosis and, therefore, future stent design. (An optical coherence tomography study to determine stent coverage in polymer coated versus bare metal rapamycin eluting

  18. GUESSmix-guided optimization of elution-extrusion counter-current separations.

    PubMed

    Friesen, J Brent; Pauli, Guido F

    2009-05-08

    Rational strategies for the optimization of separations are vital to any chromatographic technique. In counter-current separations (CS), once a suitable solvent system is selected for a given separation, the operator is faced with the task of optimizing the separation through the manipulation of those adjustable operation parameters allowed for by the current CS technology. This study employed a mixture of 21 natural products of varying polarity, molecular mass, and functionality, termed the GUESSmix, as a tool to assess the effectiveness of optimization strategies. The behavior of the GUESSmix was observed in the hexane/ethyl acetate/methanol/water 4:6:4:6 (HEMWat +3) solvent system. The effect of operation parameters on both the elution and extrusion stages of a recently introduced CS methodology, termed elution-extrusion counter-current chromatography (EECCC), was investigated. The resulting chromatograms were plotted with K-based reciprocal symmetry plots (ReS and ReSS), which allow comparison of the K values of significant peaks and assessment of resolution of eluting compounds in the interval 0< or =K< or =infinity. The operation parameters studied were: (1) the effect of temperature controlled water circulation around the centrifuge; (2) the combination of flow rate and revolution speed; (3) sample loading capacity; (4) the direction of rotation either agreeing with or opposing the direction of coil winding; (5) injection before equilibration, a practice that saves operator time and reduces solvent consumption. The GUESSmix was found to be a highly useful reference mixture to compare and contrast stationary phase retention volume ratios, resolution, K-values, peak shapes, and extrusion characteristics between CS experiments. EECCC is shown to be a robust technique that may be enhanced with appropriate temperature, rpm, flow rate, sample loading, direction of rotation, and injection timing. Plotting ReS[S] chromatograms enables systematic study of CS

  19. 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

  20. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Miniaturized Self-Expanding Drug-Eluting Stent in Small Coronary Arteries: Late Effectiveness

    PubMed Central

    de Oliveira, Flavio Roberto Azevedo; Mattos, Luiz Alberto Piva e; Abizaid, Alexandre; Abizaid, Andrea S.; Costa, J. Ribamar; Costa, Ricardo; Staico, Rodolfo; Botelho, Roberto; Sousa, J. Eduardo; Sousa, Amanda

    2013-01-01

    Background Small vessels represent a risk factor for restenosis in percutaneous coronary angioplasty (PCA). The Sparrow® self-expanding drug-eluting stent, which has a lower profile than the current systems, has never been tested in this scenario. Objectives To evaluate the late effectiveness of the Sparrow® drug-eluting stent, regarding in-stent late lumen loss (LLL). Methods Patients with ischemia, symptomatic or documented, were submitted to PCA in vessels with reference diameter < 2.75 mm, divided into two groups regarding Sparrow® stent type: group 1: Sparrow® drug-eluting stent (DES), group 2: Sparrow® bare metal stent (BMS). Clinical follow-up duration was 12 months. Evaluation using quantitative coronary angiography (QCA) was performed immediately and at 8 months. A decrease of over 65% of in-stent LLL with DES was estimated to calculate sample size. IBM® SPSS software, release 19 (Chicago, Illinois, USA) was used for the statistical analysis. Results A total of 24 patients were randomized, 12 in each group. The DES and BMS groups were similar in age (63.25 ± 10.01 vs. 64.58 ± 11.54, p = 0.765), male gender (58.3% vs. 33.3%, p = 0.412), risk factors and all angiographs aspects. Immediate results were satisfactory in both groups. At 8 months in-stent late lumen loss was significantly lower in DES than in BMS group (DES vs. BMS 0.25 ± 0.16 0.97 ± 0.76, p = 0.008). Conclusion In small-vessel PCA, the Sparrow® DES determined significant reduction in in-stent LLL, when compared to Sparrow® BMS. PMID:24100691

  2. Extended Outcomes of Complex Coronary Disease in the Drug Eluting Stent Era

    PubMed Central

    Desrosiers, Kevin P.; Brown, Jeremiah R.; Langner, Craig A.; Sidhu, Mandeep S.; Robb, John F.; Hearne, Michael J.; Lee, Peter M. Ver; Kellett, Mirle A.; Ryan, Thomas J.; O’Meara, John R.; Dauerman, Harold L.; Silver, M. Theodore; Thompson, Craig A.; Malenka, David J.

    2011-01-01

    Background Several randomized trials comparing bare-metal stents to Drug-Eluting Stents (DES) have demonstrated a significant reduction in Target Vessel Revascularization (TVR) and Target Lesion Revascularization (TLR) exists with the use of drug-eluting stents, without compromising survival. These conclusions are based on restricted inclusion criteria for patients and lesion. It is unknown if these results can be generalized to an unselected patient population and more complex disease. The objective of this study was to determine to what extent the availability of DES has impacted survival, TVR, and TLR in a large regional experience without the restriction of on-label indications. Methods Patients registered with the Northern New England Cardiovascular Disease Study Group’s PCI registry with single vessel coronary disease undergoing a first PCI were sorted according to the Bare-Metal stent (BMS) era (2001 - 2002) or the Drug-Eluting stent (DES) era (2004 - 2005) based on the time period their first PCI took place. Totally, 6,093 BMS and 5,651 DES patients were identified. Outcomes of survival, TLR and TVR were measured after one year. Results After 1 year, survival was comparable, TLR was reduced by 4.9% (absolute) and TVR was reduced by 5.4% (absolute) in the DES era compared to the BMS era. The TLR/TVR differences remained significant after propensity matching in the DES era vs BMS era (Mortality: HR 1.00, 95% CI: 0.83 - 1.28; TLR: HR 0.40, 95% CI 0.32 - 0.46; TVR: HR 0.44, 95% CI 0.38 - 0.51). Conclusions In large regional experience with a consecutive series of patients representing the contemporary practice of PCI, including both on and off label use, the frequent use of DES reduces the risk of TVR and TLR without compromising survival.

  3. Peak spreading in linear gradient elution chromatography with a thin monolithic disk.

    PubMed

    Yamamoto, Shuichi; Okada, Tomomi; Abe, Mitsuyo; Yoshimoto, Noriko

    2011-04-29

    The peak spreading of DNAs of various sizes [12-mer, 20-mer, 50-mer and 95-mer poly(T)] in linear gradient elution (LGE) chromatography with a thin monolithic disk was investigated by using our method developed for determining HETP in LGE. Electrostatic interaction-based chromatography mode (ion-exchange chromatography, IEC) was used. Polymer-based monolithic disks of two different sizes (12 mm diameter, 3mm thickness and 0.34 mL; 5.2 mm diameter, 4.95 mm thickness and 0.105 mL) having anion-exchange groups were employed. For comparison, a 15-μm porous bead IEC column (Resource Q, 6.4mm diameter, 30 mm height and 0.97 mL) was also used. The peak width did not change with the flow velocity for the monolithic disks where as it became wider with increasing velocity. For the monolithic disks the peak width normalized with the column bed volume was well-correlated with the distribution coefficient at the peak position K(R). HETP values were constant (ca. 0.003-0.005 cm) when K(R)>5. Much higher HETP values which are flow-rate dependent were obtained for the porous bead chromatography. It is possible to obtain 50-100 plates for the 3mm monolithic disk. This results in very sharp elution peaks (standard deviation/bed volume=0.15) even for stepwise elution chromatography, where the peak width is similar to that for LGE of a very steep gradient slope. Copyright © 2011 Elsevier B.V. All rights reserved.

  4. Elution of Clindamycin and Enrofloxacin From Calcium Sulfate Hemihydrate Beads In Vitro.

    PubMed

    Phillips, Heidi; Boothe, Dawn M; Bennett, R Avery

    2015-11-01

    To compare the in vitro elution characteristics of clindamycin and enrofloxacin from calcium sulfate hemihydrate beads containing a single antibiotic, both antibiotics, and each antibiotic incubated in the same eluent well. Experimental in vitro study. Calcium sulfate hemihydrate beads were formed by mixing with clindamycin and/or enrofloxacin to create 4 study groups: (1) 160 mg clindamycin/10 beads; (2) 160 mg enrofloxacin/10 beads; (3) 160 mg clindamycin + 160 mg enrofloxacin/10 beads; and (4) 160 mg clindamycin/5 beads and 160 mg enrofloxacin/5 beads. Chains of beads were formed in triplicate and placed in 5 mL phosphate buffered saline (PBS; pH 7.4 and room temperature) with constant agitation. Antibiotic-conditioned PBS was sampled at 14 time points from 1 hour to 30 days. Clindamycin and enrofloxacin concentrations in PBS were determined using high-performance liquid chromatography. Eluent concentrations from clindamycin-impregnated beads failed to remain sufficiently above minimum inhibitory concentration (MIC) for common infecting bacteria over the study period. Enrofloxacin eluent concentrations remained sufficiently above MIC for common wound pathogens of dogs and cats and demonstrated an atypical biphasic release pattern. No significant differences in elution occurred as a result of copolymerization of the antibiotics into a single bead or from individual beads co-eluting in the same eluent well. Clindamycin-impregnated beads cannot be recommended for treatment of infection at the studied doses; however, use of enrofloxacin-impregnated beads may be justified when susceptible bacteria are cultured. © Copyright 2015 by The American College of Veterinary Surgeons.

  5. Quantitation of specific proteins in polyacrylamide gels by the elution of Fast Green FCF.

    PubMed

    Gilmore, L B; Hook, G E

    1981-07-01

    The quantitation of proteins in polyacrylamide gels stained with Fast green FCF has been investigated using a modification of the elution technique originally described by Fenner et al. (Fenner, C., Traut, R.R., Mason, D.T. and Wikman-Coffelt, J. (1975) Anal. Biochem. 63, 595--602) for Coomassie Blue and adapted by Medugorac (Medugorac, I. (1979) Basic Res. Cardiol. 74, 406--416) for use with proteins stained with Fast Green FCF. The elution of dye from stained protein was accomplished using 1.0 M NaOH instead of aqueous pyridine as required by the original method. The primary advantages of our modification are that the time required for protein quantitation has been considerably reduced and the use of toxic organic solvents has been eliminated. We have investigated the applicability of the method of several different proteins and our results indicate: (a) The quantity of Fast Green FCF eluted from specific proteins is proportional to the quantity of protein applied to the gel, but varies for each individual protein. (b) The method allows quantitation over a very wide range of protein (1--800 micrograms). (c) Quantitation of protein is independent of the width of the stained bands as well as acrylamide concentration. (d) The method is applicable to gels of many types including disc, slab and continuous gradient gels. (e) Protein can be estimated from the patterns obtained by two-dimensional polyacrylamide gel electrophoresis. (f) The presence of Triton X-100 in gel and protein sample does not affect quantitation; the method is applicable to gels containing SDS provided that SDS is removed prior to staining. (g) Precipitation of protein with 12.5% TCA following electrophoresis does not interfere with quantitation. (h) The reproducibility of the technique is excellent, with standard deviations being less than 10% of the mean in all cases. This method appears highly versatile but requires appropriate standards for the quantitation of individual proteins.

  6. Performance of the Orsiro Hybrid drug-eluting stent in high-risk subgroups.

    PubMed

    Iglesias, Juan F; Muller, Olivier; Zuffi, Andrea; Eeckhout, Eric

    2016-02-01

    Newer-generation drug-eluting stents (DES) with enhanced biocompatibility that deliver antiproliferative drugs from a durable polymer have significantly improved safety and efficacy outcomes, compared with both early-generation DES and bare-metal stents, and they represent the current standard of care in all patient and lesion subsets. However, newer durable polymers have been associated with the occurrence of chronic inflammation, delayed vascular healing, incomplete endothelialisation, and neoatherosclerosis, which may result in persistent late adverse cardiovascular events, particularly in patients with high-risk baseline clinical features and angiographic complex coronary artery disease. Newer-generation DES with biodegradable polymer and controlled drug release have been recently introduced to overcome long-term adverse outcomes observed with both early-generation and newer-generation permanent polymer-based DES, and they may be of incremental clinical value in subgroups of patients at higher risk of stent failure. The recent ultrathin-strut cobalt-chromium Orsiro Hybrid DES (BIOTRONIK AG, Bülach, Switzerland) eluting sirolimus from a biodegradable polymer was designed to improve arterial healing and clinical outcomes. The Orsiro Hybrid DES has demonstrated clinical performance comparable to the current state-of-the-art newer-generation thin-strut cobalt-chromium, permanent polymer-based everolimus-eluting stent in a broad patient population. In subgroups of patients at highest-risk of adverse ischemic events, such as patients with diabetes mellitus, small vessels, long lesions, complex coronary lesions, multivessel disease, chronic total occlusion, or ST-segment elevation myocardial infarction, the Orsiro Hybrid DES has shown low rates of adverse clinical outcomes, similar to rates observed in lower-risk patients, and extremely low rates of definite stent thrombosis. This article reviews current evidence on safety and efficacy of the recent ultrathin

  7. Extended follow-up following "full-metal jacket" percutaneous coronary interventions with drug-eluting stents.

    PubMed

    Basavarajaiah, Sandeep; Naganuma, Toru; Latib, Azeem; Hasegawa, Tasuku; Sharp, Andrew; Rezq, Ahmed; Sticchi, Alessandro; Figini, Filipo; Amato, Antonio; Colombo, Antonio

    2014-12-01

    To report very long-term follow-up of "Full-Metal Jacket" (FMJ) percutaneous coronary interventions (PCI) in long-diffuse coronary lesions with drug-eluting stents (DES). PCI for long-diffuse lesions may result in FMJ, which is not preferred by some operators due to long-term risk of restenosis and stent thrombosis. The data on long-term follow-up of patients with FMJ are limited and would be useful in understanding the safety and feasibility of such a strategy. Between April 2002 and March 2007, 274 patients (297 lesions in native coronary arteries) underwent PCI utilizing DES. FMJ was described as lesions requiring ≥ 60 mm of continuous stent. The measured endpoints were cardiac death, target-vessel myocardial infarction (MI), target lesion revascularization (TLR), target-vessel revascularization (TVR), and major adverse cardiac events (MACE) defined as composite of cardiac death, target-vessel MI, and TVR. The mean age of patients was 62.1 ± 11 years. The mean length of total stents used was 75.1 ± 16.4 mm (60-150). During the median follow-up of 74.7 months (interquartile range: 58-96), the rates of cardiac death, MI, TLR, and TVR were: 5.8% (n = 16), 6.2% (n = 17), 27.3% (n = 81), and 30% (n = 89), respectively. The MACE rate was 34%. Definite and probable stent thrombosis occurred in 10 patients (3.6%). The long-term follow-up of patients with FMJ is acceptable especially in regards to hard endpoints (death and MI) given the complexity of lesions treated. The high MACE rate was driven mainly by TVR. The availability of newer-generation DES and bioabsorbable scaffolds may improve these results. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

  8. Optimal conditions for elution of hepatitis B antigen after absorption onto colloidal silica.

    PubMed Central

    Pillot, J; Goueffon, S; Keros, R G

    1976-01-01

    Hepatitis B surface antigen (HBSAg) adsorbed from sera onto colloidal silica could be completely eluted through the use of 0.25% sodium deoxycholate in 0.01 M borax, pH 9.3, at 56 degrees C. The HBSAg recovered in the eluate represented 100% of that present in the original serum, and it was contaminated by only trace amounts of serum proteins (in decreasing amounts: beta-lipoprotein, immunoglobulin G, albumin). This preliminary step greatly facilitates purification of large amounts of HBSAg and provides small volumes of highly concentrated material for subsequent purification by density gradient centrifugation. PMID:9423

  9. 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.

  10. Real-world use of drug-eluting stents: the importance of registries.

    PubMed

    Ribeiro, Expedito E; Ribeiro, Henrique Barbosa

    2010-07-01

    Over the last decades the efficacy and safety of bare metal (BMS) and drug eluting stents (DES) have been demonstrated in many different clinical scenarios, leading to their use in more than 75% of the procedures worldwide. Compared to BMS, DES have shown lower rates of angiographic restenosis and target-vessel revascularization. This benefit was initially demonstrated in trials that excluded patients with more complex lesions, such as those with larger or smaller vessels, chronic total occlusions, bifurcation lesions, stent restenosis, long lesions and left main coronary artery disease. This real-world population has been recently evaluated in many registries and meta-analyses that are reviewed herein.

  11. Concentration and Purification of Viruses by Adsorption to and Elution from Insoluble Polyelectrolytes

    PubMed Central

    Wallis, Craig; Melnick, Joseph L.; Fields, Joseph E.

    1971-01-01

    Acid-resistant, nonenveloped viruses belonging to the enterovirus, reovirus, and adenovirus groups were readily concentrated on PE60, an insoluble cross-linked polyelectrolyte based on isobutylene maleic anhydride. Hydrolysis of PE60 by NaOH increased its capacity to adsorb viruses. Hydrogen ion levels played an important role in virus concentration; optimal pH levels for maximal virus adsorption were between pH 3.0 and 4.5. Undiluted virus was easily concentrated from large volumes on PE60, and the adsorbed virus was readily eluted at pH 8 to 9. PMID:4325020

  12. 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.

  13. Ten-minute purification of PCR products by continuous elution electrophoresis.

    PubMed

    Sadakane, Yutaka; Nakagomi, Kazuya; Hatanaka, Yasumaru

    2008-10-01

    We optimized continuous elution electrophoresis (CEE) for rapid purification of PCR products. After PCR amplification, the reaction mixture is applied directly to CEE, and then the PCR products in the size range from 200 to 1500 bp are purified within nearly 10 min. CEE is able to separate two DNA fragments differing in length by 50 bp. As judged by ligation efficiency, the quality of PCR products separated by CEE is equal to that purified by extraction from the melting gels. CEE reduces operational time because purification of the PCR products is a repetitional procedure in recombinant DNA techniques.

  14. Novel drug-eluting stents in the treatment of de novo coronary lesions

    PubMed Central

    Capodanno, Davide; Dipasqua, Fabio; Tamburino, Corrado

    2011-01-01

    Due to safety concerns in recent years, much effort has been devoted to improving the outcomes associated with drug-eluting stents (DESs). This review summarizes the current status of methodological and technical achievements reported in second-generation DES. Novel stents are described based on the component (the platform, the polymer, and the drug) that has undergone the most significant changes compared to earlier generation DES. An overview of the currently available evidence on the use of novel coronary devices in patients undergoing coronary revascularization is also reviewed. PMID:21415924

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

    NASA Astrophysics Data System (ADS)

    Kumar, Sachin; Chatterjee, Kaushik

    2015-01-01

    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.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

  16. 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.

  17. Drug eluting balloons for the treatment of coronary artery disease: What can we expect?

    PubMed Central

    Joost, Alexander; Kurowski, Volkhard; Radke, Peter W

    2010-01-01

    Drug-eluting balloons (DEBs) represent an enhancement of the therapeutic repertoire for the interventional cardiologist. The therapeutic concept of DEBs is promising, notably on the basis of initial studies in patients with diffuse in-stent restenosis (ISR). At present, however, a number of questions regarding long-term efficacy and safety remain, specifically in indications other than diffuse ISR. The results of the evaluation of different substances, balloon systems and clinical indications will determine the long-term success of DEBs. PMID:21160601

  18. A case of active peri-stent inflammation after sirolimus-eluting stent implantation.

    PubMed

    Kurosawa, Takafumi; Kotani, Jun-Ichi; Matsuyama, Taka-aki; Ishibashi-Ueda, Hatsue

    2015-03-01

    We report an autopsy case of a coronary aneurysm with massive adventitial inflammation post-percutaneous coronary intervention with sirolimus-eluting stent (SES) insertion in the left circumflex (LCX) coronary artery for ischemic heart disease 3 years prior to death. The internal elastic membrane was disrupted opposite the site of the eccentric LCX plaque due to injury during stenting, and the adventitia showed massive inflammatory cell infiltration, mainly consisting of eosinophils. The LCX showed aneurysmal dilatation with inflammatory cell infiltration. Inappropriate SES implantation attracted chronic inflammation. Chronic inflammation can lead to the development of coronary artery aneurysms.

  19. Three-year follow-up of patients with bifurcation lesions treated with sirolimus- or everolimus-eluting stents: SEAside and CORpal cooperative study.

    PubMed

    Pan, Manuel; Burzotta, Francesco; Trani, Carlo; Medina, Alfonso; Suárez de Lezo, Jose; Niccoli, Giampaolo; Romero, Miguel; Porto, Italo; Mazuelos, Francisco; Leone, Antonio Maria; Martín, Pedro; Coluccia, Valentina; Suárez de Lezo, Javier; Ojeda, Soledad; Crea, Filippo

    2014-10-01

    To compare the 3-year incidence of major events in patients with bifurcation lesions treated with provisional sirolimus-eluting stents vs everolimus-eluting stents. A pooled analysis of 2 prospective randomized trials with similar methodology (SEAside and CORpal) was performed. In these trials, 443 patients with bifurcation lesions were randomly assigned to treatment with either sirolimus-eluting stents or everolimus-eluting stents. The clinical follow-up was extended up to 3 years to assess major adverse cardiovascular events (death or acute myocardial infarction or target vessel revascularization). At 3 years, survival free of major adverse cardiovascular events was 93.2% vs 91.3% in the everolimus-eluting stent group vs the sirolimus-eluting stent group (P = .16). Exploratory land-mark analysis for late events (occurring after 12 months) showed significantly fewer major adverse cardiovascular events in the everolimus-eluting stent group: 1.4% vs 5.4% in the sirolimus-eluting stent group (P = .02). Provisional stenting with either sirolimus-eluting stents or everolimus-eluting stents in bifurcation lesions is associated with low rates of major adverse events at 3-years' follow-up. The results of a subanalysis of events beyond 1 year, showing a lower event rate with everolimus-eluting stents than with sirolimus-eluting stents, suggest that studies exploring the long-term clinical benefit of the latest generation of drug-eluting stents are warranted. Copyright © 2013 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  20. Stent thrombosis and major clinical events at 3 years after zotarolimus-eluting or sirolimus-eluting coronary stent implantation: a randomised, multicentre, open-label, controlled trial.

    PubMed

    Camenzind, Edoardo; Wijns, William; Mauri, Laura; Kurowski, Volkhard; Parikh, Keyur; Gao, Runlin; Bode, Christoph; Greenwood, John P; Boersma, Eric; Vranckx, Pascal; McFadden, Eugene; Serruys, Patrick W; O'Neil, William W; Jorissen, Brenda; Van Leeuwen, Frank; Steg, Ph Gabriel

    2012-10-20

    We sought to compare the long-term safety of two devices with different antiproliferative properties: the Endeavor zotarolimus-eluting stent (E-ZES; Medtronic, Inc) and the Cypher sirolimus-eluting stent (C-SES; Cordis, Johnson & Johnson) in a broad group of patients and lesions. Between May 21, 2007 and Dec 22, 2008, we recruited 8791 patients from 36 recruiting countries to participate in this open-label, multicentre, randomised, superiority trial. Eligible patients were those aged 18 years or older undergoing elective, unplanned, or emergency procedures in native coronary arteries. Patients were randomly assigned to either receive E-ZES and C-SES (ratio 1:1). Randomisation was stratified per centre with varying block sizes of four, six, or eight patients, and concealed with a central telephone-based or web-based allocation service. The primary outcome was definite or probable stent thrombosis at 3 years and was analysed by intention to treat. Patients and investigators were aware of treatment assignment. This trial is registered with ClinicalTrials.gov, number NCT00476957. PROTECT randomised 8791 patients, of whom 8709 provided consent to participate and were eligible: 4357 were allocated to the E-ZES group and 4352 patients to the C-SES group. At 3 years, rates of definite or probable stent thrombosis did not differ between groups (1·4% for E-ZES [predicted: 1·5%] vs 1·8% [predicted: 2·5%] for C-SES; hazard ratio [HR] 0·81, 95% CI 0·58-1·14, p=0·22). Dual antiplatelet therapy was used in 8402 (96%) patients at discharge, 7456 (88%) at 1 year, 3041 (37%) at 2 years, and 2364 (30%) at 3 years. No evidence of superiority of E-ZES compared with C-SES in definite or probable stent thrombosis rates was noted at 3 years. Time analysis suggests a difference in definite or probable stent thrombosis between groups is emerging over time, and a longer follow-up is therefore needed given the clinical relevance of stent thrombosis. Medtronic, Inc. Copyright © 2012

  1. 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

  2. Polymer-free amphilimus-eluting stent versus biodegradable polymer biolimus-eluting stent in patients with and without diabetes mellitus.

    PubMed

    Godino, Cosmo; Pivato, Carlo Andrea; Chiarito, Mauro; Donahue, Michael; Testa, Luca; Colantonio, Riccardo; Cappelletti, Alberto; Milazzo, Diego; Parisi, Rosario; Nicolino, Annamaria; Moshiri, Shahram; Aprigliano, Gianfranco; Palloshi, Altin; Zavalloni Parenti, Dennis; Rutigliano, David; Locuratolo, Nicola; Melillo, Francesco; Scotti, Andrea; Arrigoni, Luca; Montorfano, Matteo; Fattori, Rossella; Presbitero, Patrizia; Sardella, Gennaro; Bedogni, Francesco; Margonato, Alberto; Briguori, Carlo; Colombo, Antonio

    2017-10-15

    This study sought to compare clinical outcome of polymer-free amphilimus-eluting stent (PF-AES) versus biodegradable-polymer biolimus-eluting stent (BD-BES) in "all-comer" diabetes mellitus (DM) and non-DM patients who underwent percutaneous coronary intervention. The PF-AES has shown promising preliminary results in patients with DM. Data from 2 multicentre-national registries (the ASTUTE and the INSPIRE-1) were used to analyse 1776 patients stratified in non-DM and DM. A double 1:1 propensity-score matched analysis (PF-AES vs. BD-BES) was performed in each group to adjust for clinical and procedural characteristics. Primary stent-efficacy and stent-safety endpoints were 1-year target-lesion revascularization (TLR) and target-lesion failure (TLF, composed of cardiac-death, target-vessel myocardial infarction and any TLR). After propensity-score matching, 850 patients were stratified as non-DM (425 PF-AES/425 BD-BES) and 480 as DM patients (240 PF-AES/240 BD-BES). Both TLF (20 of 425 [5%] vs. 24 of 425 [6%]; Plog-rank=0.527) and TLR (9 of 425 [2%] vs. 18 of 425 [4%]; Plog-rank=0.079) were similar between PF-AES and BD-BES in non-DM patients. In DM, TLF (12 of 240 [5%] vs. 31 of 240 [13%]; Plog-rank=0.002) and TLR (9 of 240 [4%] vs. 21 of 240 [9%]; Plog-rank=0.019) were significantly lower in PF-AES compared to BD-BES. Upon multivariate analysis, the most powerful predictors of TLF were chronic kidney disease in non-DM (OR 4.24, 95% CI: 2.07-8.70, p<0.001) and stent type in DM patients (OR 2.76, 1.36-5.56, p=0.005). This matched-cohort study suggests that PF-AES has better safety and efficacy profile than BD-BES in patients with DM. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Primary endpoint results of the EVOLVE trial: a randomized evaluation of a novel bioabsorbable polymer-coated, everolimus-eluting coronary stent.

    PubMed

    Meredith, Ian T; Verheye, Stefan; Dubois, Christophe L; Dens, Joseph; Fajadet, Jean; Carrié, Didier; Walsh, Simon; Oldroyd, Keith G; Varenne, Olivier; El-Jack, Seif; Moreno, Raul; Joshi, Anita A; Allocco, Dominic J; Dawkins, Keith D

    2012-04-10

    This study sought to compare the safety and efficacy of 2 dose formulations of SYNERGY, a novel bioabsorbable polymer everolimus-eluting stent (EES) (Boston Scientific Corp., Natick, Massachusetts) compared with the durable polymer PROMUS Element EES (Boston Scientific Corp.). Durable polymer coatings on drug-eluting stents have been associated with chronic inflammation and impaired healing. Bioabsorbable polymer-coated drug-delivery systems may reduce the risk of late adverse events, including stent thrombosis, and thus the need for prolonged dual-antiplatelet therapy. A total of 291 patients with a de novo lesion ≤28 mm in length, in a coronary artery of ≥2.25 to ≤3.5 mm diameter, were enrolled in the EVOLVE study, a prospective, randomized, single-blind, noninferiority trial. Patients were randomly assigned in a 1:1:1 ratio to PROMUS Element, SYNERGY, or SYNERGY half dose. The primary clinical endpoint was the 30-day rate of target lesion failure, defined as cardiac death or myocardial infarction related to the target vessel, or target lesion revascularization. The primary angiographic endpoint was 6-month in-stent late loss measured by quantitative coronary angiography. The 30-day primary clinical endpoint of target lesion failure occurred in 0%, 1.1%, and 3.1% of patients in the PROMUS Element, SYNERGY, and SYNERGY half dose groups, respectively. The 6-month in-stent late loss was 0.15 ± 0.34 mm for PROMUS Element, 0.10 ± 0.25 mm for SYNERGY, and 0.13 ± 0.26 mm for SYNERGY half dose (SYNERGY, difference -0.06, upper 95.2% confidence limit: 0.02, p for noninferiority <0.001; SYNERGY half dose, difference -0.03, upper 95.2% confidence limit: 0.05, p for noninferiority <0.001). Clinical event rates remained low and comparable between groups, with no stent thromboses in any group at 6 months. The EVOLVE trial confirms the effective delivery of everolimus by a unique directional bioabsorbable polymer system utilizing the SYNERGY stent. (A Prospective

  4. Use of Drug-Eluting Stents in Patients With Coronary Artery Disease and Renal Insufficiency

    PubMed Central

    El-Menyar, Ayman A.; Al Suwaidi, Jassim; Holmes, David R.

    2010-01-01

    Renal insufficiency (RI) has been shown to be associated with increased major adverse cardiovascular events after percutaneous coronary intervention. We reviewed the impact of RI on the pathogenesis of coronary artery disease and outcomes after percutaneous coronary intervention in the form of drug-eluting stent (DES) implantation in these high-risk patients. We searched the English-language literature indexed in MEDLINE, Scopus, and EBSCO Host research databases from 1990 through January 2009, using as search terms coronary revascularization, drug-eluting stent, and renal insufficiency. Studies that assessed DES implantation in patients with various degrees of RI were selected for review. Most of the available data were extracted from observational studies, and data from randomized trials formed the basis of a post hoc analysis. The outcomes after coronary revascularization were less favorable in patients with RI than in those with normal renal function. In patients with RI, DES implantation yielded better outcomes than did use of bare-metal stents. Randomized trials are needed to define optimal treatment of these high-risk patients with coronary artery disease. PMID:20118392

  5. Nanoporous CREG-Eluting Stent Attenuates In-Stent Neointimal Formation in Porcine Coronary Arteries

    PubMed Central

    Sun, Mingyu; Tao, Jie; Yan, Chenghui; Kang, Jian; Li, Shaohua

    2013-01-01

    Background The goal of this study was to evaluate the efficacy of a nanoporous CREG-eluting stent (CREGES) in inhibiting neointimal formation in a porcine coronary model. Methods In vitro proliferation assays were performed using isolated human endothelial and smooth muscle cells to investigate the cell-specific pharmacokinetic effects of CREG and sirolimus. We implanted CREGES, control sirolimus-eluting stents (SES) or bare metal stents (BMS) into pig coronary arteries. Histology and immunohistochemistry were performed to assess the efficacy of CREGES in inhibiting neointimal formation. Results CREG and sirolimus inhibited in vitro vascular smooth muscle cell proliferation to a similar degree. Interestingly, human endothelial cell proliferation was only significantly inhibited by sirolimus and was increased by CREG. CREGES attenuated neointimal formation after 4 weeks in porcine coronary model compared with BMS. No differences were found in the injury and inflammation scores among the groups. Scanning electron microscopy and CD31 staining by immunohistochemistry demonstrated an accelerated reendothelialization in the CREGES group compared with the SES or BMS control groups. Conclusions The current study suggests that CREGES reduces neointimal formation, promotes reendothelialization in porcine coronary stent model. PMID:23573278

  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. Selection and elution of aptamers using nanoporous sol-gel arrays with integrated microheaters.

    PubMed

    Park, Seung-Min; Ahn, Ji-Young; Jo, Minjoung; Lee, Dong-Ki; Lis, John T; Craighead, Harold G; Kim, Soyoun

    2009-05-07

    RNA and DNA aptamers that bind to target molecules with high specificity and affinity have been a focus of diagnostics and therapeutic research. These aptamers are obtained by SELEX (Systematic Evolution of Ligands by EXponential enrichment) often requiring more than 10 successive cycles of selection and amplification, where each cycle normally takes 2 days per cycle of SELEX. Here, we have demonstrated the use of sol-gel arrays of proteins in a microfluidic system for efficient selection of RNA aptamers against multiple target molecules. The microfluidic chip incorporates five sol-gel binding droplets, within which specific target proteins are imbedded. The droplets are patterned on top of individually addressable electrical microheaters used for selective elution of aptamers bound to target proteins in the sol-gel droplets. We demonstrate that specific aptamers bind their respective protein targets and can be selectively eluted by micro-heating. Finally, our microfluidic SELEX system greatly improved selection efficiency, reducing the number of selection cycles needed to produce high affinity aptamers. The process is readily scalable to larger arrays of sol-gel-embedded proteins. To our knowledge, this is the first demonstration of a chip-based selection of aptamers using microfluidics, thereby allowing development of a high throughput and efficient SELEX procedures.

  8. Chiral separation with gradient elution isotachophoresis for future in situ extraterrestrial analysis.

    PubMed

    Danger, Grégoire; Ross, David

    2008-10-01

    The first results of chiral separations with the gradient elution isotachophoresis method are presented. As previously described, citrate is used in the run buffer as the leading ion and borate in the sample buffer as the terminating ion. Modulation of parameters such as electrolyte pH, pressure scan rate, chiral selector concentration, combinations of CD or the percentage of ampholytes provides an easy optimization of the separations. To perform fluorescent detection 5-carboxyfluorescein succinimidyl ester and two fluorogenic-labeling agents, fluorescamine (Fluram) and 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde, are used to label amino acids. With the 5-carboxyfluorescein amino acids, chiral separations are easily obtained using a neutral CD ((2-hydroxypropyl)-beta-CD) at a low concentration (2 mmol/L). With Fluram amino acids, the situation is more complicated due to the formation of diastereoisomers and due to weak interactions with the different CDs used. The use of the 3-(4-carboxybenzoyl)quinoline-2-carboxaldehyde-labeling agent solves the problems observed with the Fluram agent while retaining the fluorogenic properties. These first results demonstrate the simplicity and the feasibility of gradient elution isotachophoresis for chiral separations.

  9. 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.

  10. Effect of Atorvastatin-Eluting Stents in a Rabbit Iliac Artery Restenosis Model

    PubMed Central

    Lim, Kyung Seob; Bae, In Ho; Park, Jun-Kyu; Park, Dae Sung; Kim, Jong Min; Kim, Jung Ha; Cho, Dong Lyun; Sim, Doo Sun; Park, Keun-Ho; Hong, Young Joon; Ahn, Youngkeun

    2013-01-01

    Statins have pleiotropic effects, which include the inhibition of neointima hyperplasia, the inhibition of vascular inflammation, and platelet inhibition. The aim of this study was to examine the effect of an atorvastatin-eluting stent (AES) in a rabbit iliac artery overstretch restenosis model. Ten rabbits were used in this study (10 rabbits, 10 iliac arteries for each stent). An AES and paclitaxel-eluting stent (PES) were implanted in the left and right iliac arteries in a rabbit (2 stents in each rabbit). The stents were deployed with oversizing (stent/artery ratio 1.3:1), and histopathologic analysis was assessed at 28 days after stenting. There were no significant differences in the injury score, lumen area, or inflammation score. There were significant differences in the neointimal area (0.7±0.18 mm2 in the AES group vs. 0.4±0.25 mm2 in the PES group, p<0.01), in the percentage stenosis area (14.8±5.06% in the AES group vs. 10.5±6.80% in the PES group, p<0.05), and in the fibrin score (0.4±0.51 in the AES group vs. 2.7±0.48 in the PES group, p<0.001). Although the AES did not suppress neointimal hyperplasia compared with the PES, it showed a superior arterial healing effect in a rabbit iliac artery overstretch restenosis model. PMID:24400214

  11. Infrared microspectroscopy analysis of ibuprofen release from drug eluting beads in uterine tissue.

    PubMed

    Namur, J; Wassef, M; Pelage, J P; Lewis, A; Manfait, M; Laurent, A

    2009-05-05

    Ibuprofen loaded embolization beads (IBU-BB) have been developed to reduce inflammation and pain following uterine artery embolization for the treatment of uterine fibroids. The present work has investigated the elution properties of IBU-BB in situ after embolization with Fourier Transform Infrared Microspectroscopy (FTIRMS). Twelve sheep underwent uterine artery embolization with IBU-BB (485 mM) or control unloaded beads. IBU concentration was determined inside the beads and in the tissue surrounding the beads using FTIRMS of uterine tissue sections sampled 24 h or 1 week after embolization. After 24 h, IBU concentration inside the bead was only 18.6 mM out of the 485 mM initially loaded (p < 0.0001, univariate sign test). The concentration in the tissue around the beads was 8 mM, which is well above the in vitro therapeutic levels (6 microM). After one week the concentration of IBU had decreased to 4.9 mM in the beads (p = 0.0502, Mann Whitney) and no IBU was detected in the surrounding tissue. This work has demonstrated that IBU-BB can provide a sustained release of the anti-inflammatory drug over at least one week. The in vivo elution properties of IBU-BB may be suitable to alleviate pain and inflammation after embolization.

  12. Computer-assisted transfer of programmed elutions in reversed-phase high-performance liquid chromatography.

    PubMed

    García-Lavandeira, J; Martínez-Pontevedra, J A; Lores, M; Cela, R

    2006-09-22

    Computer-assisted procedures were used to simulate modifications in chromatograms caused by the transfer of elution programmes between instruments with significantly different dwell volumes. Moreover, for the first time the same approach was used to modify the elution programmes to match the chromatograms produced in the different instruments. The process may consist of making minor modifications to gradient programmes or transforming the original gradient programme into a stepwise gradient profile and/or the simultaneous programming of flow and solvent composition. The combination of these approaches has been shown to have an enormous potential for producing matched chromatograms in instrumental systems with dwell volumes that differ by several millilitres. The efficiency and robustness of the proposed procedure is demonstrated with a variety of compounds (two different mixtures of 10 and 11 analytes), mobile phases (methanol and acetonitrile gradients), flow rates (0.5-1.5 mL/min range), temperatures (35-45 degrees C interval) and gradient profiles (linear, multilinear, curved and stepwise).

  13. Impact of metabolic syndrome on re-stenosis development: role of drug-eluting stents.

    PubMed

    Goyal, S N; Bharti, S; Krishnamurthy, B; Agrawal, Y; Ojha, S K; Arya, D S

    2012-07-01

    Metabolic syndrome (MetS) is defined as a cluster of numerous cardiovascular risk factors, which encompasses obesity, dyslipidaemia, insulin resistance and hypertension. Patients with MetS are more prone to developing cardiovascular events than other patients. To date, several approaches such as physical exercise, dietary control and invasive and non-invasive therapeutic interventions for dyslipidaemia, hypertension and insulin resistance have been used to manage MetS. However, there is a progressive elevation in the incidence of fatal and non-fatal cardiovascular events due to the increased prevalence of obesity and diabetes. Percutaneous coronary intervention has emerged over the last few years as an effective revascularisation strategy for those with coronary artery disease, in parallel with the development of effective anti-platelet medications and newer drug-eluting stents. In recent years, considerable research efforts have been undertaken to elucidate the pathophysiology of re-stenosis and develop strategies to prevent re-stenosis following percutaneous transluminal coronary angioplasty and stent implantation. Although the rate of stent re-stenosis and target-lesion revascularisation has been reduced, there is little information in the literature on the outcome of MetS in the pathophysiology of re-stenosis. In this review article, we summarise the recent development and progress on re-stenosis and the role of drug-eluting stents, particularly in MetS.

  14. Drug-eluting stent: the "magic bullet" for prevention of restenosis?

    PubMed

    Hehrlein, Christoph; Arab, Amina; Bode, Christoph

    2002-11-01

    The need for repeat interventions after initially successful PTCA due to restenosis has been called the "Archilles heel" of a percutaneous revascularization procedure. The incidence of restenosis varies between 20-50 % depending on the stent material, the presence of risk factors, and the location of vascular disease. Some risk factors such as diabetes have been clearly identified, others are currently debated. After years of failures trying to reduces restenosis rates, locally administered antiproliferative means have been shown to successfully inhibit excessive cell growth in response to PTCA. Local radiotherapy of in-stent restenosis results in a reduction of recurrent stenosis versus a conventional PTCA procedure. However, long-term evaluation indicated that restenosis may only be delayed with radiation therapy. Moreover, the restenosis rates were reduced, but the restenotic process was not eliminated. Coronary stents eluting the anti-proliferative agent rapamycin have demonstrated for the first time, that restenosis rates of zero percent are achievable after percutaneous revascularization procedures. Thus, it is intriguing to believe that the elimination of restenosis may have become reality. The purpose of this review is to discuss, whether a stent eluting drugs should be considered as the "magic bullet" for prevention of restenosis after PTCA.

  15. Modelling chemistry and biology after implantation of a drug-eluting stent. Part I: Drug transport.

    PubMed

    Vo, Tuoi; Lee, William; Peddle, Adam; Meere, Martin

    2017-04-01

    Drug-eluting stents have been used widely to prevent restenosis of arteries following percutaneous balloon angioplasty. Mathematical modelling plays an important role in optimising the design of these stents to maximise their efficiency. When designing a drug-eluting stent system, we expect to have a sufficient amount of drug being released into the artery wall for a sufficient period to prevent restenosis. In this paper, a simple model is considered to provide an elementary description of drug release into artery tissue from an implanted stent. From the model, we identified a parameter regime to optimise the system when preparing the polymer coating. The model provides some useful order of magnitude estimates for the key quantities of interest. From the model, we can identify the time scales over which the drug traverses the artery wall and empties from the polymer coating, as well as obtain approximate formulae for the total amount of drug in the artery tissue and the fraction of drug that has released from the polymer. The model was evaluated by comparing to in-vivo experimental data and good agreement was found.

  16. Retention studies of DNA on anion-exchange monolith chromatography Binding site and elution behavior.

    PubMed

    Yamamoto, Shuichi; Nakamura, Masashi; Tarmann, Christina; Jungbauer, Alois

    2007-03-09

    Linear gradient elution experiments were carried out on monolithic anion-exchange chromatography (AEC) with oligo-DNAs of various sizes (4-50mer, molecular weight M(W)=1200-15,000) and compositions in order to investigate the retention mechanism. The binding site (B) values as well as the peak salt elution concentration I(R) values were determined. The B values determined for the monolithic AEC were similar to the values for non-porous AEC and porous AEC. The B value increased linearly with the number of charges (bases) of single-strand DNA when M(W) is less than ca. 3600 (12mer). When M(W) is greater than 6000, the slope of B versus M(W) decreased, and became very small at M(W)>30,000. The I(R) value also increased linearly with M(W) for M(W)<6000, and slightly with M(W) for M(W)>10,000. It was shown that a very difficult separation of a single-strand 50mer poly(T) and a double-strand 50mer poly(A) and poly(T) was accomplished within 10 min by using a very shallow gradient at a high initial salt concentration (0.5M) and a high flow-velocity (2.7 cm/min).

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

    PubMed

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

    2016-07-05

    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. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Perioperative management of a patient with recently placed drug-eluting stents requiring urgent spinal surgery.

    PubMed

    Roth, Eira; Purnell, Chad; Shabalov, Olga; Moguillansky, Diego; Hernandez, Caridad A; Elnicki, Michael

    2012-08-01

    Patients receiving drug-eluting coronary stents (DES) require antiplatelet therapy for at least 12 months to prevent stent thrombosis (ST), a potentially calamitous event. Since interruption of antiplatelet therapy is the greatest risk factor for ST, it is imperative that the decision to discontinue these agents be based on an accurate assessment of the patient's risk for bleeding complications. Individuals who are regarded as being at a high risk are those undergoing intracranial, spinal or intraocular surgeries. These patients require alternative agents during the perioperative period to minimize both their risk of perioperative thrombosis and intraoperative hemorrhage. We report the case of a woman who required spinal surgery 3 months after she underwent placement of two drug-eluting stents. The patient's clopidogrel was stopped 5 days prior to surgery and an infusion of eptifibatide was used to "bridge" antiplatelet therapy during the perioperative period. Postoperatively, anticoagulation therapy was reinstituted using aspirin with clopidogrel. This case serves as a successful example of bridging therapy using a short acting and gycoprotein (GP) IIb/IIIa inhibitor as a means of maintaining antiplatelet therapy during the perioperative period to minimize the risk of stent thrombosis and the risk of intraoperative bleeding.

  19. Transarterial chemoembolization using 40 µm drug eluting beads for hepatocellular carcinoma

    PubMed Central

    Greco, Giorgio; Cascella, Tommaso; Facciorusso, Antonio; Nani, Roberto; Lanocita, Rodolfo; Morosi, Carlo; Vaiani, Marta; Calareso, Giuseppina; Greco, Francesca G; Ragnanese, Antonio; Bongini, Marco A; Marchianò, Alfonso V; Mazzaferro, Vincenzo; Spreafico, Carlo

    2017-01-01

    AIM To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment. METHODS Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation (OLT). This allowed for histological analysis on the treated explanted nodules. RESULTS DEB-TACE with 40 μm showed a good safety profile without major complications or 30-d mortality. The objective response rate of treated tumors was 72.6% and 26.7% according to mRECIST and RECIST respectively. Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases. The overall time to progression was 13 mo (11-21). CONCLUSION DEB-TACE with 40 μm particles is an effective treatment for the treatment of HCC in early-intermediate patients (Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis. PMID:28634515

  20. Transarterial chemoembolization using 40 µm drug eluting beads for hepatocellular carcinoma.

    PubMed

    Greco, Giorgio; Cascella, Tommaso; Facciorusso, Antonio; Nani, Roberto; Lanocita, Rodolfo; Morosi, Carlo; Vaiani, Marta; Calareso, Giuseppina; Greco, Francesca G; Ragnanese, Antonio; Bongini, Marco A; Marchianò, Alfonso V; Mazzaferro, Vincenzo; Spreafico, Carlo

    2017-05-28

    To assess the safety and efficacy of transarterial chemoembolization (TACE) of hepatocellular carcinoma (HCC) using a new generation of 40 μm drug eluting beads in patients not eligible for curative treatment. Drug eluting bead TACE (DEB-TACE) using a new generation of microspheres (embozene tandem, 40 μm) preloaded with 100 mg of doxorubicin was performed on 48 early or intermediate HCC patients with compensated cirrhosis. Response to therapy was assessed with Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST) guidelines applied to computed tomography or magnetic resonance imaging. Eleven out of the 48 treated patients treated progressed on to receive liver orthotopic transplantation (OLT). This allowed for histological analysis on the treated explanted nodules. DEB-TACE with 40 μm showed a good safety profile without major complications or 30-d mortality. The objective response rate of treated tumors was 72.6% and 26.7% according to mRECIST and RECIST respectively. Histological examination in 11 patients assigned to OLT showed a necrosis degree > 90% in 78.6% of cases. The overall time to progression was 13 mo (11-21). DEB-TACE with 40 μm particles is an effective treatment for the treatment of HCC in early-intermediate patients (Barcelona Clinic Liver Cancer stage A/B) with a good safety profile and good results in term of objective response rate and necrosis.

  1. 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.

  2. 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.

  3. Locoregional Drug Delivery Using Image-guided Intra-arterial Drug Eluting Bead Therapy

    PubMed Central

    Lewis, Andrew L.; Dreher, Matthew R.

    2012-01-01

    Lipiodol-based transarterial chemoembolization (TACE) has been performed for over 3 decades for the treatment of solid tumors and describes the infusion of chemotherapeutic agents followed by embolization with particles. TACE is an effective treatment for inoperable hepatic tumors, especially hypervascular tumors such as hepatocellular carcinoma. Recently, drug eluting beads (DEBs), in which a uniform embolic material is loaded with a drug and delivered in a single image-guided step, have been developed to reduce the variability in a TACE procedure. DEB-TACE results in localization of drug to targeted tumors while minimizing systemic exposure to chemotherapeutics. Once localized in the tissue, drug is eluted from the DEB in a controlled manner and penetrates hundreds of microns of tissue from the DEB surface. Necrosis is evident surrounding a DEB in tissue days to months after therapy; however, the contribution of drug and ischemia is currently unknown. Future advances in DEB technology may include image-ability, DEB size tailored to tumor anatomy and drug combinations. PMID:22285550

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

    PubMed

    Kumar, Sachin; Chatterjee, Kaushik

    2015-02-07

    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.

  5. Alternative sample-introduction technique to avoid breakthrough in gradient-elution liquid chromatography of polymers.

    PubMed

    Reingruber, Eva; Bedani, Filippo; Buchberger, Wolfgang; Schoenmakers, Peter

    2010-10-15

    Gradient-elution liquid chromatography (GELC) is a powerful tool for the characterization of synthetic polymers. However, gradient-elution chromatograms often suffer from breakthrough phenomena. Breakthrough can be averted by using a sample solvent as weak as the mobile phase. However, this approach is only applicable to polymers for which a sufficiently strong solvent exists which is at the same time a weak eluent. Finding such a solvent for a given polymer can be laborious or may even be impossible. Besides, when working with comprehensive two-dimensional LC the effluent of the first dimension is the injection solvent of the second dimension. In this case, it is not possible to avoid breakthrough by adjusting the eluent strength of the second-dimension injection solvent. Therefore, another strategy to avert breakthrough has to be implemented. In this work, we successfully avoided breakthrough in GELC by mixing the mobile phase not before, but after the autosampler. This was demonstrated measuring a blend of poly(methyl methacrylate) standards with different molecular-weights as model mixture with comprehensive two-dimensional GELC×size-exclusion chromatography. The strategy is thought to be applicable to all substances with a sufficiently strong dependence of retention on mobile-phase composition. This typically applies to large molecules (synthetic and natural polymers) and allows efficient refocusing. Unretained and barely retained substances are not refocused and therefore suffer in the proposed setup from peak broadening. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Bead Based Proteome Enrichment Enhances Features of the Protein Elution Plate (PEP) for Functional Proteomic Profiling

    PubMed Central

    Wang, Xing; Davies, Michael; Roy, Swapan; Kuruc, Matthew

    2015-01-01

    A novel functional proteomics technology called PEP(Protein Elution Plate) was developed to separate complex proteomes from natural sources and analyze protein functions systematically. The technology takes advantage of the powerful resolution of two-dimensional gel electrophoresis (2-D Gels). The modification of electrophoretic conditions in combination with a high-resolution protein elution plate supports the recovery of functionally active proteins. As 2DE(2-Dimensional Electrophoresis) resolution can be limited by protein load, we investigated the use of bead based enrichment technologies, called AlbuVoid™ and KinaSorb™ to determine their effect on the proteomic features which can be generated from the PEP platform. Using a variety of substrates and enzyme activity assays, we report on the benefits of combining bead based enrichment to improve the signal report and the features generated for Hexokinase, Protein Kinase, Protease, and Alkaline Phosphatase activities. As a result, the PEP technology allows systematic analysis of large enzyme families and can build a comprehensive picture of protein function from a complex proteome, providing biological insights that could otherwise not be observed if only protein abundances were analyzed. PMID:28248280

  7. Fabrication of a novel polymer-free nanostructured drug-eluting coating for cardiovascular stents.

    PubMed

    Wang, Yao; Zhang, Wenli; Zhang, Jixi; Sun, Wei; Zhang, Ruiyan; Gu, Hongchen

    2013-10-23

    Angioplasty with stents is the most important method for the treatment of coronary artery disease (CAD). However, the drug-eluting stents (DES) that are widely used have the increased risks of inflammatory reactions and late stent thrombosis (LST) because of the persistence of the polymer coatings. To improve the biosafety, a novel polymer-free-composite drug-eluting coating composed of magnetic mesoporous silica nanoparticles (MMSNs) and carbon nanotubes (CNTs) was constructed using the electrophoretic deposition (EPD) method in this study. A crack-free two-layered coating with impressive network nanotopologies was successfully obtained by regulating the composition and structures. This nanostructured coating exhibits excellent mechanical flexibility and blood compatibility in vitro, and the drug-loading and release performance is satisfactory as well. The in vivo study shows that this composite coating has the obvious advantage of rapid endothelialization because of its unique 3D nanostructured topology in comparison with the commercial polymer-coated DES. This study aims to provide new ideas and reliable data to design novel functional coatings that could accelerate the re-endothelialization process and avoid inflammatory reactions, thus improving the in vivo biosafety of DES.

  8. MMPI drug-eluting IVC filter decreases adhesion between caval wall and filter.

    PubMed

    Xiao, Liang; Wang, Man

    2013-03-01

    The implantation of inferior vena cava (IVC) filter was a safe and effective therapy for preventing fatal pulmonary embolism. However, there are risks associated with long-term implantation of filters. Retrievable filters are designed to be removed, but may also remain permanently. Retrieval can reduce risk of long-term complications. The difficulty or impossibility of retrieval is still an issue of retrieval filter. The major causes of filters retrieval failure were intimal overgrowth and severely tilted filter with apex embedded into the caval wall. Matrix metalloproteinases (MMPs) play a key role in neointimal hyperplasia. It is documented that neointimal hyperplasia can be reduced by inhibiting MMP activity and hence smooth muscle cell migration. MMP inhibitors (MMPI) can potently inhibit the activity of MMPs. We hypothesize that a drug-eluting filter which contains MMPI may inhibit IVC neointimal hyperplasia and decrease the adhesion between vascular wall and filter struts. After implantation of drug-eluting retrieval filter, MMPI is released slowly at the sites where the filter struts are in contact with the caval wall; the activity of MMPs of caval wall will be inhibited, injury in basement membrane is decreased, migration of SMC maybe reduced, and the release of extracellular matrix maybe lessened. Finally, neointimal hyperplasia maybe inhibited, the adhesion between vascular wall and filter maybe weakened, the success rate maybe increased, and the vascular injury during retrieval maybe reduced. The hypothesis might improve the long-term prognosis of venous thromboembolism patients.

  9. 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

  10. Mechanical Properties and Elution Characteristics of Polymethylmethacrylate Bone Cement Impregnated with Antibiotics for Various Surface Area and Volume Constructs

    PubMed Central

    Duey, Richard E.; Chong, Alexander CM.; McQueen, David A.; Womack, James L.; Song, Zheng; Steinberger, Tristan A.; Wooley, Paul H.

    2012-01-01

    Background Numerous studies have examined the elution characteristics and the effects of antibiotics from bone cement. this study seeks to determine the effect that surface area and volume have on the elution characteristics and bioavailability of tobramycin and vancomycin when mixed in polymethylmethacralate (PMMA) bone cement in various combinations. It also investigates the mechanical properties of antibiotic-impregnated bone cement and its relationship to surface area and volume. Methods Three antibiotic-bone cement combinations were used, and these consisted of PMMA mixed with tobramycin and vancomycin or tobramycin alone. Four groups of specimens (different surface area and volume) were made. the elution characteristics of the different specimens were examined using the minimum inhibitory concentration (MIc) method at different time intervals. the bacteria used during testing were methicillin-sensitive staphylococcus aureus (MssA). the ultimate compressive strength (Ucs) of the specimens was also determined at various time intervals. Results the bactericidal activity of a tobramycin/vancomycin combination against MssA was not significantly greater than tobramycin alone. tobramycin was more effective than vancomycin against MssA (average: 168%, p<0.05). the inhibitory capabilities of tobramycin and vancomycin individually were not found to be additive. combination 2 (1.0g tobramycin/1.0g vancomycin) had a higher antibiotic elution mass and rate for all sample sizes compared to the other two combinations (average: 170%, p<0.05). surface area and volume did not have a significant effect on the elution rate of the antibiotics. the Ucs of all samples tested was greater than 70MPa at all three testing intervals. Discussion Mixing tobramycin and vancomycin did not have a synergistic effect against the bacteria as expected. Increasing the concentration of antibiotics in bone cement increases both elution mass and elution rate over time. Although the Ucs of the

  11. 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

    2015-11-03

    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.

  12. Binding site and elution behavior of DNA and other large biomolecules in monolithic anion-exchange chromatography.

    PubMed

    Yamamoto, Shuichi; Yoshimoto, Noriko; Tarmann, Christina; Jungbauer, Alois

    2009-03-27

    Our previous study has shown that there is a good correlation between the number of charges of DNA (from trimer to 50-mer) and the number of binding sites B in electrostatic interaction chromatography (ion-exchange chromatography, IEC). It was also found that high salt (NaCl) concentration is needed to elute large DNAs (>0.6M). In this paper we further performed experiments with large DNAs (up to 95-mer polyT and polyA) and charged liposome particles of different sizes (ca. 30, 50 and 100 nm) with a monolithic anion-exchange disk in order to understand the binding and elution mechanism of very large charged biomolecules or particles. The peak salt (NaCl) concentration increased with increasing DNA length. However, above 50-mer DNAs the value did not increase significantly with DNA length (ca. 0.65-0.70 M). For liposome particles of different sizes the peak salt concentration (ca. 0.62 M) was similar and slightly lower than that for large DNAs (ca. 0.65-0.70 M). The binding site values (ca. 25-30) are smaller than those for large DNAs. When arginine was used as a mobile phase modulator, the elution position of polyA and polyT became very close whereas in NaCl gradient elution polyT appeared after polyA eluted. This was mainly due to suppression of hydrophobic interaction by arginine.

  13. Safety and efficacy of the Yukon Choice Flex sirolimus-eluting coronary stent in an all-comers population cohort

    PubMed Central

    Xhepa, E.; Tada, T.; Cassese, S.; King, L.; Ott, I.; Fusaro, M.; Kastrati, A.; Byrne, R.A.

    2014-01-01

    Aims The use of biodegradable-polymer drug-eluting stents has been shown to provide favorable results when compared with durable polymer drug-eluting stents and long-term follow up data have recently shown significant reductions in terms of very late stent thrombosis. Aim of the present study was to assess the safety and efficacy profile of a novel biodegradable polymer DES, the Yukon Choice Flex sirolimus-eluting stent. Methods We report here the one-year clinical outcomes associated with the use of the Yukon Choice Flex sirolimus-eluting stent in an all-comers patient population. The present stent represents a further refinement of the stent platform tested in the ISAR TEST 3 and 4 randomized clinical trials. A total of 778 consecutive patients undergoing implantation of this stent were enrolled in the present observational study and prospectively followed for one year. Results The use of the Yukon Choice Flex stent in a patient population with complex coronary lesion morphology was associated with optimal immediate angiographic results. At one year follow up the rates of death, myocardial infarction, definite stent thrombosis and ischemia-driven target lesion revascularization were respectively 2.4%, 1.9%, 0.3% and 11.3%. Conclusions The use of the sirolimus-eluting biodegradable polymer Yukon Choice Flex stent in an all-comers population of patients with complex coronary artery disease is associated with a favorable safety and efficacy profile up to one year follow up. PMID:24973842

  14. The effects of hitchhiker antigens co-eluting with affinity-purified research antibodies.

    PubMed

    Mechetner, Lilly; Sood, Radhika; Nguyen, Van; Gagnon, Pete; Parseghian, Missag H

    2011-09-01

    The popularity of Protein G for the purification of antibodies has given rise to an entire industry that supplies scientists with research grade immunoreagents; however, many times the supplied product is contaminated with antigens bound to the antibody's complementarity-determining regions (CDRs). These "hitchhikers" are a category of host cell proteins that are elusive to detect due to their interaction with the antibody in the final product and yet their impact on an experiment or an entire field of study can be far reaching. In an earlier work, the role of hitchhikers on a human anti-histone antibody destined for clinical usage was explored and a stringent purification scheme developed. Here we use a murine monoclonal, which reflects the type of commercial antibody usually purchased for research. We evaluate three purification schemes: a traditional approach using a one-step, low pH elution buffer (pH 2.5); a gentler approach using a pH gradient elution scheme (pH 7 down to pH 2.5); and finally, a more stringent purification patterned on our earlier published method that uses a quaternary amine guard column and a high salt wash during antibody immobilization on the Protein G. We stress that the stringent purification incorporates the pH gradient scheme and is gentler than the low-pH approach. The resulting product from all three purifications is directly compared for binding potency, histone content (using an ELISA based assay) and residual DNA (using quantitative PCR). The results demonstrate that the first two methods are inadequate for hitchhiker removal. The traditional one-step, low pH approach produces a single elution peak containing histone contaminated antibody with picogram quantities of residual DNA, however, the trailing end of the same peak is loaded with antibody complexed to nanogram amounts of DNA, in some cases, over 100 ng. The pH gradient approach provided antibodies accompanied by only picograms of residual DNA and, on average, 1 out of

  15. Development of Online pH Gradient-Eluted Strong Cation Exchange Nanoelectrospray-Tandem Mass Spectrometry for Proteomic Analysis Facilitating Basic and Histidine-Containing Peptides Identification.

    PubMed

    Xu, Jingjing; Gao, Jing; Yu, Chengli; He, Han; Yang, Yiming; Figeys, Daniel; Zhou, Hu

    2016-01-05

    A novel one-dimensional online pH gradient-eluted strong cation exchange-nanoelectrospray ionization-tandem mass spectrometry (SCX-nano-ESI-MS/MS) method was developed for protein identification and tested with a mixture of six standard proteins, total lysate of HuH7 and N2a cells, as well as membrane fraction of N2a cells. This method utilized an online nanoflow SCX column in a nano-LC system coupled with a nanoelectrospray high-resolution mass spectrometer. Protein digests were separated on a nanoflow SCX column with a pH gradient and directly introduced into a mass spectrometer through nanoelectrospray ionization. More than five thousand unique peptides were identified in each 90 min LC-MS/MS run using 500 nanogram of protein digest either from total cell lysate or from membrane fraction. The unique peptide overlap between online strong cation exchange nano-ESI-MS/MS (SCXLC-MS/MS) and reverse phase nano-ESI-MS/MS (RPLC-MS/MS) is only ≤30%, which indicated these two methods were complementary to each other. The correlation coefficient of retention time and theoretical isoelectric point (pI) of identified peptides in SCXLC-MS/MS was higher than 0.4, which showed that peptides elution in SCXLC-MS/MS was dependent on their charge states. Furthermore, SCXLC-MS/MS showed identification capability for a higher proportion of basic peptides compared to the RPLC-MS/MS method, especially for histidine-containing peptides. Our SCXLC-MS/MS method is an excellent alternative method to the RPLC-MS/MS method for analysis of standard proteins, total cell and membrane proteomes.

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

    PubMed

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

    2001-04-20

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

  17. Sirolimus-Eluting Stents vs Uncoated Stents for the Treatment of Proximal Left Anterior Descending Coronary Artery Stenosis

    PubMed Central

    Valencia, José; Mainar, Vicente; Bordes, Pascual; Berenguer, Alberto; Ruiz-Nodar, Juan Miguel; Pineda, Javier; Gomez, Silvia; Sogorb, Francisco; Caturla, Juan

    2007-01-01

    Sirolimus-eluting stents (SES) have demonstrated low incidence of target vessel revascularizations in several anatomic scenarios, including proximal left anterior descending coronary artery (pLAD) lesions. The aim of present study was to compare the efficacy of SES with bare metal stents (BMS) for the treatment of such lesions. 96 patients with severe pLAD stenosis treated with SES were included. Clinical follow-up were performed during a 24 month period. A 98 patient sample with pLAD lesions treated with BMS was taken as control group. Death, angiographic restenosis, new target lesion revascularization (TLR) and target vessel failure (TVF) were registered. Clinical, angiographic and procedural variables were analysed to identify predictors of TVF and TLR. Angiographic procedural success was 100% in SES group vs 99% in BMS group (p=1.0). At 2.5 years, the cumulative rate of TVF was 9.4% in SES group vs 16.3% in BMS group (p=0.15), and the rate of TLR was 5.2% in SES group vs 12.2% in control group (p=0.08). The probabilities of cumulative TVF and TLR free survival were in BMS group 83.7% and 87.8%, and in SES group 90.6% and 94.8%, respectively. After multivariate analysis only SES utilization was found as independent protective factor against TVF and TLR (HR 0.38, 95%CI [0.15-0.94] p=0.037 and HR 0.21, 95%CI [0.06-0.66] p=0.008, respectively), and diabetes as independent predictor of TFV and TLR (HR 2.37, 95%CI [1.07-5.24] p=0.034 and HR 3.57, 95%CI [1.29-9.87] p=0.014, respectively). This study demonstrates that SES utilization is safe and effective in the tretament of pLAD lesions with a better clinical outcome than BMS in a long-term follow-up. PMID:23675052

  18. Comparison of paclitaxel and everolimus-eluting stents in ST-segment elevation myocardial infarction and influence of thrombectomy on outcomes. ESTROFA-IM study.

    PubMed

    de la Torre Hernández, José M; Alfonso, Fernando; Martin Yuste, Victoria; Sánchez Recalde, Angel; Jimenez Navarro, Manuel F; Pérez de Prado, Armando; Hernández, Felipe; Abdul-Jawad Altisent, Omar; Roura, Gerard; García Camarero, Tamara; Elizaga, Jaime; Calviño, Ramón; Moreu, Jose; Bosa, Francisco; Jimenez Mazuecos, Jesús; Ruiz-Arroyo, José R; Garcia Del Blanco, Bruno; Rumoso, José R

    2014-12-01

    We sought to compare the long-term clinical outcome of with ST-segment elevation myocardial infarction treated with paclitaxel-eluting stents or everolimus-eluting stents and the influence of thrombectomy on outcomes. The ESTROFA-IM is a multicenter retrospective registry collecting consecutive patients with infarction treated with these stents in 16 centers. Propensity-score matching was performed to select comparable stent groups and comparable groups with and without thrombectomy. After matching patients, 350 treated with everolimus-eluting stents and 350 with paclitaxel-eluting stents were included in the analysis. The clinical and angiographic characteristics were comparable in both groups. The 2-year incidence of death, infarction, and target lesion revascularization was 14.9% for paclitaxel-eluting stents and 11.5% for everolimus-eluting stents (P = .04) and the incidence of definite/probable thrombosis 4.3% and 1.4%, respectively (P = .01). The use of paclitaxel-eluting was an independent predictor for events (hazard ratio = 2.44, 95% confidence interval, 1.28-4.65; P = .006). The benefit of everolimus-eluting stents over paclitaxel-eluting stents regarding stent thrombosis was more evident in the nonthrombectomy subgroup (5.4% vs 1.4%; P = .01). A significant interaction was found in the subgroups with and without thombectomy in the comparison between paclitaxel-eluting stents and everolimus-eluting stents for the end-point of stent thrombosis (P = .039). The results of this multicenter registry suggest better clinical outcomes with the everolimus-eluting stents in ST-segment elevation myocardial infarction. The lower risk of thrombosis with these stents could be more relevant in the absence of thrombectomy. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  19. 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

  20. DNA elution from buccal cells stored on Whatman FTA Classic Cards using a modified methanol fixation method.

    PubMed

    Johanson, Helene C; Hyland, Valentine; Wicking, Carol; Sturm, Richard A

    2009-04-01

    We describe here a method for DNA elution from buccal cells and whole blood both collected onto Whatman FTA technology, using methanol fixation followed by an elution PCR program. Extracted DNA is comparable in quality to published Whatman FTA protocols, as judged by PCR-based genotyping. Elution of DNA from the dried sample is a known rate-limiting step in the published Whatman FTA protocol; this method enables the use of each 3-mm punch of sample for several PCR reactions instead of the standard, one PCR reaction per sample punch. This optimized protocol therefore extends the usefulness and cost effectiveness of each buccal swab sample collected, when used for nucleic acid PCR and genotyping.

  1. Rapid extraction of methamphetamine and amphetamine in body fluids with Bond Elut SCX cartridges before capillary gas chromatography.

    PubMed

    Kumazawa, T; Sato, K; Seno, H; Suzuki, O

    1993-04-01

    A simple and rapid method for extraction of methamphetamine and amphetamine from human whole blood and urine with Bond Elut SCX cation exchanger cartridges is presented. Detection of the stimulants was made by capillary gas chromatography (GC) with flame ionization detection after derivatization with trifluoroactic anhydride. The compound-containing samples, after mixing with 0.05 M potassium phosphate buffer (pH 7.8), were directly applied to the cartridges, washed with 20 ml of 50% methanol in water and eluted with methanol-HCl (240:1). The recoveries of both methamphetamine and amphetamine were close to 100%. The background noises for Bond Elut SCX cartridge extraction were much smaller than those for Sep-Pak C18 cartridge and diethyl ether extractions.

  2. How do porosity-inducing techniques affect antibiotic elution from bone cement? An in vitro comparison between hydrogen peroxide and a mechanical mixer

    PubMed Central

    Lovric, V.; Leung, A.; Walsh, W. R.

    2008-01-01

    Background Increasing the porosity of an antibiotic-loaded cement spacer increases the antibiotic elution, but the correlation between porosity and antibiotic elution is not well documented. The purposes of this study was to attempt new porosity-increasing methods and to investigate the correlation between antibiotic elution and both total and surface porosity. Materials and methods Five types of antibiotic-loaded bone cement (ALBC) using 2 g cefazolin and 40 g cement were prepared. Other than manual mixing, hydrogen peroxide was used as a foaming agent and a mixing drill piece was used as a mechanical device to try to induce porosity when mixing the cement. Elution of antibiotic into phosphate-buffered saline was measured from 1 h to 1 week. Surface porosity was calculated from density values which were measured with a density kit and an electronic balance, while total porosity was quantified using micro-computed tomography. Results When a mixing drill piece was used to induce porosity, we observed a significant increasin antibiotic elution compared to a manually mixed ALBC. On the other hand, hydrogen peroxide reduced the elution significantly. Mild correlation between the total amount of cluted in 1 week antibiotic elution and total porosity was observed. Conclusions In terms of improving elution, the mixing drill piece seemed to be efficient. A relationship between surface porosity and elution efficacy was not observed. PMID:19384476

  3. Use of drug-eluting versus bare-metal stents after an acute coronary syndrome in Portugal: the EURHOBOP study.

    PubMed

    Barros, Vítor; Pereira, Marta; Araújo, Carla; Braga, Pedro; Azevedo, Ana

    2015-01-01

    The interventional cardiologist chooses a specific stent type based on the risk-benefit profile for each case. In general, drug-eluting stents should be considered in all clinical conditions, except if there are concerns or contraindications for prolonged dual antiplatelet therapy. The aim of this work was to describe the use of bare-metal vs. drug-eluting stents in patients undergoing percutaneous coronary intervention (PCI) after an acute coronary syndrome in Portuguese hospitals, according to patients' demographic and clinical characteristics and institutional characteristics. Within the EURopean Hospital Benchmarking Processes (EURHOBOP) study, we retrospectively assessed 3009 consecutive patients in 10 Portuguese hospitals in 2009. Only patients with stents implanted during PCI (n=1194) were analyzed. A total of 425 patients (36%) received a bare-metal stent and 769 patients (64%) received a drug-eluting stent. A history of previous PCI, current non-ST-elevation myocardial infarction, anterior descending artery as the infarct-related artery and being initially admitted to a hospital with a catheterization laboratory were associated with drug-eluting stent implantation. Age under 45 or over 80, anemia and previous anticoagulation and/or atrial fibrillation were associated with bare-metal stent use. Approximately two-thirds of patients received drug-eluting stents, which were less frequently implanted in patients with ST-elevation myocardial infarction, aged over 80 years, female, with a previous history of stroke, anticoagulation and/or atrial fibrillation and anemia. Patients who had previously undergone PCI and those with the anterior descending artery as the infarct-related artery were more likely to receive a drug-eluting stent. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  4. Impact of ultrasonic power density on hot water elution of severely biodegraded heavy oil from weathered soils.

    PubMed

    Ji, Guodong; Guo, Feng

    2010-03-01

    An ultrasound-enhanced elution system using water at a temperature of 70 degrees C was employed to remove severely biodegraded heavy oil (SBHO) from weathered soil. The effect of varying the ultrasonic power density from 0 to 100 W L(-1) on the elution of SBHO and three characteristic biomarkers (C(26-34) 17alpha 25-norhopanes, C(26-28) triaromatic steroids (TAS), and C(27-29) methyl triaromatic steroids (MTAS) was analyzed using GC/MS, scanning electron microscopy (SEM), and X-ray diffraction (XRD). The amount of SBHO and biomarkers present in the treated soils and eluent had significant negative correlation with increasing ultrasonic power density. Elution of the three biomarkers was closely related to the number of C atoms in the marker: C(26-34) 17alpha 25-norhopanes with more carbon numbers and MTAS homologs with less carbon numbers were more readily eluted at higher power densities. The smaller TAS species were more readily eluted at a power density of less than 60 W L(-1), while larger TAS species displayed improved elution at power densities greater than 60 W L(-1). SEM images of samples treated at higher power densities revealed a more compact SBHO accumulation layer at the water-soil interface. The results of XRD and energy spectroscopy experiments indicated that ultrasound at a power density of 20 W L(-1) was helpful for the formation and sedimentation of calcite, although this effect disappeared at higher power of greater than 60 W L(-1).

  5. Drug-eluting beads for liver embolization: concentration of doxorubicin in tissue and in beads in a pig model.

    PubMed

    Namur, Julien; Wassef, Michel; Millot, Jean-Marc; Lewis, Andrew L; Manfait, Michel; Laurent, Alexandre

    2010-02-01

    To evaluate the local tissue concentrations of the antineoplastic agent doxorubicin and the amount of drug still present inside drug delivery embolization beads at different time points after embolization and to compare doxorubicin levels with histologic modifications around the beads in a pig liver model. It was hypothesized that doxorubicin-eluting beads maintain cytotoxic concentrations of drug locally over a period of several weeks, as suggested by in vitro elution tests. Left lobe hepatic artery embolization was performed in 10 pigs with 100-300-microm or 700-900-microm beads loaded with 37.5 mg doxorubicin/mL. Control unloaded 100-300-microm beads were injected in five pigs. Livers were sampled 28 days or 90 days after embolization. The amount of drug retained inside the beads was assessed with infrared microspectroscopy. Doxorubicin concentration and distribution in the tissue around the beads were determined with microspectrofluorimetry and compared with tissue modifications on hematein eosin saffron-stained sections. Doxorubicin-eluting beads eluted 43% of their initial drug load after 28 days and 89% after 90 days. Doxorubicin was present in tissues around the beads at both time points, with a significant decrease over time (P = .0004). The drug was detected at distances as far as 600 microm from the bead edge. Doxorubicin tissue concentrations ranged from 0.55 microM to 6.80 microM, [corrected] which are cytotoxic levels in hepatocyte cell cultures. High concentrations of drug were associated with coagulative necrosis of liver parenchyma. Doxorubicin-eluting beads 100-300 microm in size induced more necrosis than 700-900-microm beads (P = .0036). Doxorubicin-eluting beads deliver high concentrations of the drug over a period of at least 3 months at several hundred micrometers from the bead, leading to significant cytotoxic effects. Copyright (c) 2010 SIR. Published by Elsevier Inc. All rights reserved.

  6. Local release of antibiotics for surgical site infection management using high-purity calcium sulfate: an in vitro elution study.

    PubMed

    Aiken, Sean S; Cooper, John J; Florance, Hannah; Robinson, Matthew T; Michell, Stephen

    2015-02-01

    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. 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. 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. Pharmaceutical-grade calcium sulfate has the potential for targeted local release of tobramycin, gentamicin, vancomycin, and rifampicin over a clinically meaningful time period.

  7. 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

  8. Paclitaxel-coated balloon for the treatment of drug-eluting stent restenosis: subanalysis results from the Valentines I trial.

    PubMed

    Loh, Joshua P; Stella, Pieter R; Sangiorgi, Giuseppe; Silber, Sigmund; Stahnke, Stefanie; von Strandmann, Rembert Pogge; Torguson, Rebecca; Waksman, Ron

    2014-01-01

    To analyze the effect of paclitaxel-coated balloon (PCB) treatment on patients with drug-eluting stent (DES) restenosis. In the Valentines I trial, treatment of coronary in-stent restenosis was effective and safe with the second-generation DIOR® PCB. Valentines I prospectively enrolled 250 patients with in-stent restenosis (ISR); 76 patients (30.4%) had restenosis of a previous paclitaxel or limus DES. Patients underwent balloon angioplasty followed by PCB treatment. Clinical outcomes of patients with paclitaxel-eluting DES restenosis (n=34; 41 lesions) and limus-eluting (sirolimus, everolimus and zotarolimus) DES restenosis (n=42; 43 lesions) treated with DIOR® PCB were compared. Baseline characteristics were similar. There were more diffuse lesions >20mm treated in paclitaxel- compared to limus-eluting DES restenosis (50% vs. 26.8%, p=0.032). Number of PCB used per patient (1.08±0.31 overall), mean PCB diameter (2.99±0.42mm overall), mean PCB length (24.4±11.9mm overall), and bailout stenting (2.4% vs. 4.7%) were similar (p=NS). At mean follow-up of 231±43days, major adverse cardiac events was 0% vs. 23.8% in paclitaxel- vs. limus-eluting DES restenosis (p=0.002), driven mainly by less target vessel revascularization (0% vs. 21.4%, p=0.004). Target lesion revascularization was 0% vs. 16.7% for paclitaxel- vs. limus-eluting DES restenosis (p=0.015). In Valentines I, PCB use was more effective in patients with paclitaxel DES restenosis compared to limus DES restenosis, achieving better mid-term clinical outcomes. This suggests the efficacy of localized paclitaxel delivery to overcome paclitaxel resistance but not limus resistance due to different mechanisms of DES failure. © 2014.

  9. Platelet reactivity over time in coronary artery disease patients treated with a bioabsorbable everolimus-eluting scaffold.

    PubMed

    Tello-Montoliu, Antonio; Rivera, José; Hernández-Romero, Diana; Silvente, Ana; Jover, Eva; Quintana, Miriam; Orenes-Piñero, Esteban; Hurtado, José; Ferreiro, José Luis; Marín, Francisco; Valdés, Mariano

    2016-12-01

    Everolimus-eluting bioabsorbable scaffolds (BVSs) have exhibited similar long-term clinical outcomes compared to its everolimus-eluting metallic counterparts. However, reports from earlier studies have shown a signal for an increased rate of stent thrombosis. The aim of the current investigation is to describe the platelet reactivity profiles over time in patients treated with everolimus-eluting BVS in comparison to everolimus-eluting metallic stents. This is a pilot study in which patients on aspirin and clopidogrel with at least 1 everolimus-eluting BVS were included (n = 24). Patients with at least 1 everolimus-eluting metallic stent implanted were included as control group (n = 25). Blood samples were taken at time of discharge and at 3- and 6-month follow-up. Platelet function tests included VerifyNow (VN-P2Y12), multiplate aggregometry (MEA), and light transmission aggregometry (LTA). There was no difference in platelet reactivity at discharge, 3- and 6-month visits (unadjusted p = 0.733 and p = 0.582; p = 0.432 and p = 0.899 after adjusting for discharge value platelet reactivity0, respectively) using VN-P2Y12. Similar findings were observed with LTA. However, patients with BVS showed significantly higher platelet reactivity than patients with metallic stents at 3 and 6 months in the crude analysis (p = 0.003) and after adjusting for discharge value (p = 0.013) measured with ADP-MEA. There were no differences in platelet reactivity mediated by the T × A2 pathway between both groups. Finally, there is no statistical difference in high on-clopidogrel platelet reactivity (HPR) rate between both groups. The results of this pilot study suggest that BVS might have different platelet reactivity profiles, and warrants further investigation in dedicated clinical studies.

  10. Separation of topological forms of plasmid DNA by anion-exchange HPLC: shifts in elution order of linear DNA.

    PubMed

    Smith, Clara R; DePrince, Randolph B; Dackor, Jennifer; Weigl, Debra; Griffith, Jack; Persmark, Magnus

    2007-07-01

    We sought to establish a single anion-exchange HPLC method for the separation of linear, open circular and supercoiled plasmid topoisomers using purified topoisomeric forms of three plasmids (3.0, 5.5 and 7.6 kb). However, finding one condition proved elusive as the topoisomer elution order was determined to depend on salt gradient slope. The observed change in selectivity increased with plasmid size and was most pronounced for the linear form. Indeed, the elution order of the linear 7.6 kb plasmid was reversed relative to the supercoiled form. This observation may have implications for methods used in quality control of plasmid DNA.

  11. 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.

  12. Elution characteristics of teicoplanin-loaded biodegradable borate glass/chitosan composite.

    PubMed

    Jia, Wei-Tao; Zhang, Xin; Zhang, Chang-Qing; Liu, Xin; Huang, Wen-Hai; Rahaman, Mohamed N; Day, Delbert E

    2010-03-15

    Local antibiotic delivery system has an advantage over systemic antibiotic for osteomyelitis treatment due to the delivery of high local antibiotic concentration while avoiding potential systemic toxicity. Composite biomaterials with multifunctional roles, consisting of a controlled antibiotic release, a mechanical (load-bearing) function, and the ability to promote bone regeneration, gradually become the most active area of investigation and development of local antibiotic delivery vehicles. In the present study, a composite of borate glass and chitosan (designated BG/C) was developed as teicoplanin delivery vehicle. The in vitro elution kinetics and antibacterial activity of teicoplanin released from BG/C composite as a function of immersion time were determined. Moreover, the pH changes of eluents and the bioactivity of the composite were characterized using scanning electron microscopy coupled with energy-dispersive spectroscopy and X-ray diffraction analysis.

  13. Endovascular techniques in limb salvage: cutting, cryo, brachy, and drug-eluting balloons.

    PubMed

    Davies, Mark G; Anaya-Ayala, Javier E

    2013-04-01

    The complex pathophysiology response to injury of the lower-extremity arteries has prompted the development of several unique balloon technologies to overcome initial technical failures and short-term intimal hyperplasia. Cryoplasty alters the cellular and mechanical properties of the vessel wall during angioplasty. Cutting balloons incise the wall, preventing elastic recoil and allowing expansion of the lumen at a lower pressure, thus limiting barotrauma. Drug-eluting balloons actively transfer inhibitory compounds to the wall during the initial therapy, while brachytherapy balloons allow for localized delivery of radiation to inhibit the proliferative response seen after angioplasty. These platforms provide unique means to enhance immediate and short-term results and also reduce stent usage in the lower extremity.

  14. Drug-eluting stents in unprotected left main coronary artery disease.

    PubMed

    Bernelli, Chiara

    2014-11-01

    Though coronary bypass graft surgery (CABG) has traditionally been the cornerstone of therapy in patients with unprotected left main coronary artery (ULMCA) disease, recent evidence supports the use of percutaneous coronary intervention in appropriate patients. Indeed in patients with ULMCA disease, drug-eluting stents (DES) have shown similar incidence of hard end points, fewer periprocedural complications and lower stroke rates compared with CABG, though at the cost of increased revascularization with time. Furthermore, the availability of newer efficacious and safer DES as well as improvements in diagnostic tools, percutaneous techniques and, importantly, a better patient selection, allowed percutaneous coronary intervention a viable alternative to CABG of left main-patients with low disease complexity; however, even in this interventional era characterized by efficacious DES, patients with ULMCA disease remain a challenging high-risk population where outcomes strongly depend on clinical characteristics, anatomical disease complexity and extension and operator's experience. This review summarizes the role of DES in ULMCA disease patients.

  15. Bioresorbable drug-eluting magnesium-alloy scaffold for treatment of coronary artery disease.

    PubMed

    Campos, Carlos M; Muramatsu, Takashi; Iqbal, Javaid; Zhang, Ya-Jun; Onuma, Yoshinobu; Garcia-Garcia, Hector M; Haude, Michael; Lemos, Pedro A; Warnack, Boris; Serruys, Patrick W

    2013-12-16

    The introduction of metallic drug-eluting stents has reduced the risk of restenosis and widened the indications of percutaneous coronary intervention in treatment of coronary artery disease. However, this medical device can induce hypersensitive reaction that interferes with the endothelialization and healing process resulting in late persistent or acquired malapposition of the permanent metallic implant. Delayed endotheliaization and malapposition may lead to late and very late stent thrombosis. Bioresorbable scaffolds (BRS) have been introduced to potentially overcome these limitations, as they provide temporary scaffolding and then disappear, liberating the treated vessel from its cage. Magnesium is an essential mineral needed for a variety of physiological functions in the human body and its bioresorbable alloy has the strength-to-weight ratio comparable with that of strong aluminum alloys and alloy steels. The aim of this review is to present the new developments in Magnesium BRS technology, to describe its clinical application and to discuss the future prospects of this innovative therapy.

  16. 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.

  17. Chromatofocusing using micropellicular column packings with computer-aided design of the elution buffer composition.

    PubMed

    Kang, Xuezhen; Frey, Douglas D

    2002-03-01

    Micropellicular, anion-exchange column packings are used in chromatofocusing to demonstrate the resolution and speed achieved when proteins are separated under these conditions. Linear or concave pH gradients are produced with simple mixtures containing four or fewer individual buffering species instead of the more commonly used polyampholyte buffers. Computer-aided design methods are demonstrated for selecting the composition of the elution buffer to produce a pH gradient of a desired shape. The method is applied to high-resolution, analytical- and preparative-scale separations involving horse myoglobin, human hemoglobin variants, and bovine carbonic anhydrase. A useful selection of buffering species is described capable of producing pH gradients of a variety of shapes in the range between pH 9.5 and 5.5.

  18. A Bumpy and Winding but Right Path to Domestic Drug-Eluting Coronary Stents

    PubMed Central

    Cho, Jae Yeong; Ahn, Youngkeun

    2013-01-01

    Restenosis and stent thrombosis remain major concerns after percutaneous coronary intervention for the treatment of coronary artery disease. The present review was undertaken in order to highlight the various coronary stents that have been investigated in our Heart Research Center, and how far we have come from the first heparin-coated stent first used in the late 1990s. Thereafter, from the abciximab-coated stent to the current gene-delivery stent and other newer agents, our group has applied a range of techniques in this field. However, in groups similar to ours, the restenosis rates of such stents are still high for second-generation drug-eluting stents (DESs). Moreover, our nation imports almost all of these types of stents from other countries. Thus, we need to develop domestic coronary stents. Research into newer DESs are warranted in Korea so as to achieve improved safety and efficacy outcomes. PMID:24255648

  19. Modified alkaline elution allows the measurement of intact apurinic sites in mammalian genomic DNA.

    PubMed

    Malvy, C; Lefrançois, M; Bertrand, J R; Markovits, J

    2000-08-01

    The presence of apurinic/apyrimidinic (AP) sites in cell genomes is known to be toxic and mutagenic. These lesions are therefore repaired in cells by efficient enzymatic systems. However, a report (Nakamura and Swenberg, Cancer Res. 59 (1999) 2522-2526) indicates an unexpected high rate of endogenous apurinic/apyrimidinic (AP) sites in genomic DNA in mammalian tissues. The technology used does not allow the authors to distinguish between intact AP sites and 3'cleaved AP sites. The corresponding values range between 2 and 4 sites per million of nucleotides in various human and rat tissues. Using a modified alkaline elution method we show here that the stationary level of intact AP sites is about 0.16 per million of nucleotides in leukemic mouse L1210 cells.

  20. MRI Visible Drug Eluting Magnetic Microspheres for Transcatheter Intra-Arterial Delivery to Liver Tumors

    PubMed Central

    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. PMID:25767615

  1. Sirolimus- versus paclitaxel-eluting stents: numero uno, first among equals or equal?

    PubMed

    Kuchulakanti, Pramod K; Waksman, Ron

    2006-07-01

    Drug-eluting stents (DESs) have shown the ability to reduce restenosis and major adverse cardiac events in de novo lesions when compared with bare metal stents in randomized studies. Enthused by the results of these trials, DESs are being used in other difficult lesion subsets, such as bifurcation lesions, in-stent restenosis, vein graft lesions and chronic total occlusions. They are also being used in difficult patient subsets, such as diabetes and acute myocardial infarction. Not all DES are equal, however, and research is now focused on understanding the differences between these stents. This review discusses the DESs that are US FDA-approved and currently available in the USA, namely Cypher (Cordis Corporation) and Taxus (Boston Scientific), and whether they are comparable.

  2. Characterization of polypropylene-polyethylene blends by temperature rising elution and crystallization analysis fractionation.

    PubMed

    Monrabal, Benjamín; del Hierro, Pilar

    2011-02-01

    The introduction of single-site catalysts in the polyolefins industry opens new routes to design resins with improved performance through multicatalyst-multireactor processes. Physical combination of various polyolefin types in a secondary extrusion process is also a common practice to achieve new products with improved properties. The new resins have complex structures, especially in terms of composition distribution, and their characterization is not always an easy task. Techniques like temperature rising elution fractionation (TREF) or crystallization analysis fractionation (CRYSTAF) are currently used to characterize the composition distribution of these resins. It has been shown that certain combinations of polyolefins may result in equivocal results if only TREF or CRYSTAF is used separately for their characterization.

  3. Expanding the elution by characteristic point method for determination of various types of adsorption isotherms.

    PubMed

    Samuelsson, Jörgen; Undin, Torgny; Fornstedt, Torgny

    2011-06-17

    Important improvements have recently been made on the elution by characteristic point (ECP) method to increase the accuracy of the determined adsorption isotherms. However, the method has so far been limited/used for only type I adsorption isotherms (e.g. Langmuir, Tóth, bi-Langmuir). In this study, general strategies are developed to expand the ECP method for the determination of more complex adsorption isotherms including such containing inflection points. We will exemplify the methodology with type II, type III and type V isotherms. Guidelines are given for how to determine such isotherms using the ECP method and for the experimental considerations that must be taken into account or that may be eliminated in the particular case.

  4. 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

  5. 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.

  6. The eternal tale of dialysis access vessels and restenosis: are drug-eluting balloons the solution?

    PubMed

    Portugaller, Rupert H; Kalmar, Peter I; Deutschmann, Hannes

    2014-01-01

    In dialysis access fistulas and grafts, percutaneous transluminal angioplasty (PTA) is frequently followed by restenosis development, which results in repeated periodical re-interventions. The technique of drug-eluting balloon (DEB) angioplasty has shown promising results in the treatment of femoropopliteal arteriosclerotic lesions. In contrast to arteriosclerotic arteries, dialysis access vessels host unfavorable hemodynamics due to the direct conduction of high-pressure fluid into a low-pressure system. Hence, the beneficial effect of DEB angioplasty may be limited in this system. However, a first prospective randomized trial on 40 patients with arteriovenous fistula or graft stenoses exhibited a significantly higher 6-month primary patency of the treated lesions after DEB angioplasty than after uncoated balloon angioplasty. Despite such a positive reference, general recommendations regarding the value of DEBs in dialysis access vessels cannot be considered as serious unless large randomized controlled trials have been performed.

  7. 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.

  8. 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.

  9. 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

    2016-05-20

    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.

  10. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Associations Between Target Lesion Restenosis and Drug-Eluting Balloon Use

    PubMed Central

    Lee, Wei-Chieh; Wu, Chiung-Jen; Chen, Yung-Lung; Chung, Wen-Jung; Hsueh, Shu-Kai; Hang, Chi-Ling; Fang, Chih-Yuan; Fang, Hsiu-Yu

    2016-01-01

    Abstract Percutaneous coronary interventions (PCIs) with drug-eluting balloons (DEBs) have emerged as an adjunctive treatment for in-stent restenosis (ISR) lesions. However, recurrent restenosis still occurs following DEB use. Our study aimed to identify the associations of target lesion restenosis following DEB use over a 1-year clinical follow-up. Between November 2011 and May 2014, 246 patients were diagnosed with coronary artery ISR in our hospital. A total of 335 coronary ISR lesions were treated with DEBs. The 1-year patent coronary artery group was defined as those with negative noninvasive examinations and no clinical symptoms, or those with no angiographic restenosis. The 1-year current restenosis group was defined as those with angiographic restenosis. Clinical results were compared between 2 groups. Univariate and multivariate cox regression analyses were performed to identify the associations of target lesion restenosis following DEB use. Patients’ average age was 64.96 ± 10.68 years, and 77.2% were men. Non-ST segment elevation myocardial infarction was more frequent as the clinical presentation in the 1-year current restenosis group, whereas stable angina was more frequent in the 1-year patent coronary artery group. The 1-year current restenosis group exhibited higher percentages of comorbidities, including hypertension, diabetes, prior myocardial infarction, heart failure, prior coronary artery bypass grafting, and end-stage renal disease (ESRD). Regardless of ostial ISR or nonostial ISR, the results of drug-eluting stent ISR were worse than those for bare-metal stent ISR. Multivariate analysis revealed that ESRD, and coronary ostial lesion, and the severity of pre-PCI stenosis were independently associated with target lesion restenosis following DEB use (P = 0.020, P = 0.009, P = 0.026, respectively). ESRD, and coronary ostial lesion, and the severity of pre-PCI stenosis were independently associated with recurrent target lesion

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

    PubMed

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

    2010-01-22

    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. 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. 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. Copyright 2009 Elsevier Inc. All rights reserved.

  13. Drug-Eluting Balloons in the Treatment of Coronary De Novo Lesions: A Comprehensive Review.

    PubMed

    Richelsen, Rasmus Kapalu Broge; Overvad, Thure Filskov; Jensen, Svend Eggert

    2016-12-01

    Drug-eluting balloons (DEBs) have emerged as a new application in percutaneous coronary intervention. DEBs have proven successful in the treatment of in-stent restenosis, but their role in de novo lesions is less clear. This paper provides a review of the current studies where DEBs have been used in coronary de novo lesions, either as part of a DEB-only strategy or in combination with another device, mainly a bare metal stent (BMS). By searching Pubmed and Embase we were able to identify 52 relevant studies, differing in design, intervention, and clinical setting, including patients with small vessel disease, bifurcation lesions, complex long lesions, acute myocardial infarction, diabetes mellitus, and elderly. In 23 studies, a DEB was combined with a BMS, 25 studies used a DEB-only strategy with only provisional BMS implantation, and four studies combined a DEB with a drug-eluting stent (DES). In the vast majority of studies, DEB in combination with BMS does not seem to improve clinical or angiographic outcome compared with DES, whereas a DEB-only strategy seems promising, especially when predilatation and geographical mismatch are taken into account. A lower risk of recurrent thrombosis with DEB compared with DES is not evident from the current studies. In conclusion, the main indication for DEB seems to be small vessel disease, especially in clinical scenarios in which a contraindication to dual antiplatelet therapy exists. The main approach should be a DEB-only strategy with only provisional bailout stenting, which has shown interesting results in different clinical scenarios. In general, larger randomized controlled studies with prolonged follow-up comparing DEB with best in class DES are warranted. Technical developments of DEBs including the use of different drugs might potentially improve the efficacy of such treatment.

  14. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. 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.

  16. Effects of fluid flow on elution of hydrophilic modifier from dialysis membrane surfaces.

    PubMed

    Matsuda, Masato; Sato, Mika; Sakata, Hiroki; Ogawa, Takahisa; Yamamoto, Ken-ichiro; Yakushiji, Taiji; Fukuda, Makoto; Miyasaka, Takehiro; Sakai, Kiyotaka

    2008-01-01

    When uremic blood flows through dialyzers during hemodialysis, dialysis membrane surfaces are exposed to shear stress and internal filtration, which may affect the surface characteristics of the dialysis membranes. In the present study, we evaluated changes in the characteristics of membrane surfaces caused by shear stress and internal filtration using blood substitutes: water purified by reverse osmosis and 6.7 wt% dextran70 solution. We focused on the levels of a hydrophilic modifier, polyvinylpyrrolidone (PVP), on the membrane surface measured by attenuated total reflectance Fourier transform infrared spectroscopy. Experiments involving 4 h dialysis, 0-144 h shear-stress loading, and 4 h dead-end filtration were performed using polyester-polymer alloy (PEPA) and polysulfone (PS) membranes. After the dialysis experiments with accompanying internal filtration, average PVP retention on the PEPA membrane surface was 93.7% in all areas, whereas that on the PS membrane surface was 98.9% in all areas. After the shear-stress loading experiments, PVP retention on the PEPA membrane surface decreased as shear-stress loading time and the magnitude of shear stress increased. However, with the PS membrane, PVP retention scarcely changed. After the dead-end filtration experiments, PVP retention decreased in all areas for both PEPA and PS membranes, but PVP retention on the PEPA membrane surface was lower than that on the PS membrane surface. PVP on the PEPA membrane surface was eluted by both shear stress and internal filtration, while that on the PS membrane surface was eluted only by internal filtration.

  17. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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

  20. Polymer-based paclitaxel-eluting coronary stents. Clinical results in de novo lesions.

    PubMed

    Chieffo, Alaide; Colombo, Antonio

    2004-03-01

    Drug-eluting stents (DES) represent one of the fastest-growing fields in interventional cardiology today. Paclitaxel (Taxol) is a potent antiproliferative agent that shifts the microtubule equilibrium toward assembly, favoring the formation of abnormally stable microtubules with blockage of the cell cycle in G2/M phases. A series of clinical trials (TAXUS I through VI) have been designed to test the safety and the efficacy of polymer- based paclitaxel-eluting stents (Taxus, Boston Scientific, Natick, MA, USA) at the dosage 1 microg/mm(2) in a variety of clinical settings. Except for TAXUS III and TAXUS V-ISR, in the TAXUS program de novo lesions have been evaluated. Two different release kinetics were evaluated: slow-release (SR) and moderate- release (MR) formulation. Very encouraging preliminary results also come from the "real world" data on Taxus SR stent collected in the "Web-based taxus Intercontinental obServational Data TransitiOnal registry prograM" (the WISDOM Registry) and in the "Real Life Polymer-Based Paclitaxel Registry" (the Real Life PBPaclitaxel Registry). The remarkable positive results obtained from the randomized trials offer the interventional cardiologist another effective option (besides the Cypher stent, Cordis a J & J, Warren, NJ, USA) to treat patients with a DES. This fact may certainly drive the competition and, ultimately, lower the cost. The final answer will probably come from the ongoing registries and prospective trials versus coronary artery bypass grafting (CABG), which will reveal the real impact of this new technology on everyday practice.