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Sample records for high drug entrapment

  1. Entrapment of alpha1-acid glycoprotein in high-performance affinity columns for drug-protein binding studies.

    Science.gov (United States)

    Bi, Cong; Jackson, Abby; Vargas-Badilla, John; Li, Rong; Rada, Giana; Anguizola, Jeanethe; Pfaunmiller, Erika; Hage, David S

    2016-05-15

    A slurry-based method was developed for the entrapment of alpha1-acid glycoprotein (AGP) for use in high-performance affinity chromatography to study drug interactions with this serum protein. Entrapment was achieved based on the physical containment of AGP in hydrazide-activated porous silica supports and by using mildly oxidized glycogen as a capping agent. The conditions needed for this process were examined and optimized. When this type of AGP column was used in binding studies, the association equilibrium constant (Ka) measured by frontal analysis at pH 7.4 and 37°C for carbamazepine with AGP was found to be 1.0 (±0.5)×10(5)M(-1), which agreed with a previously reported value of 1.0 (±0.1)×10(5)M(-1). Binding studies based on zonal elution were conducted for several other drugs with such columns, giving equilibrium constants that were consistent with literature values. An entrapped AGP column was also used in combination with a column containing entrapped HSA in a screening assay format to compare the binding of various drugs to AGP and HSA. These results also agreed with previous data that have been reported in literature for both of these proteins. The same entrapment method could be extended to other proteins and to the investigation of additional types of drug-protein interactions. Potential applications include the rapid quantitative analysis of biological interactions and the high-throughput screening of drug candidates for their binding to a given protein. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Thermosensitive liposomes entrapping iron oxide nanoparticles for controllable drug release

    International Nuclear Information System (INIS)

    Tai, L-A; Wang, Y-C; Wang, Y-J; Yang, C-S; Tsai, P-J; Lo, L-W

    2009-01-01

    Iron oxide nanoparticles can serve as a heating source upon alternative magnetic field (AMF) exposure. Iron oxide nanoparticles can be mixed with thermosensitive nanovehicles for hyperthermia-induced drug release, yet such a design and mechanism may not be suitable for controllable drug release applications in which the tissues are susceptible to environmental temperature change such as brain tissue. In the present study, iron oxide nanoparticles were entrapped inside of thermosensitive liposomes for AMF-induced drug release while the environmental temperature was maintained at a constant level. Carboxyfluorescein was co-entrapped with the iron oxide nanoparticles in the liposomes as a model compound for monitoring drug release and environmental temperature was maintained with a water circulator jacket. These experiments have been successfully performed in solution, in phantom and in anesthetized animals. Furthermore, the thermosensitive liposomes were administered into rat forearm skeletal muscle, and the release of carboxylfluorescein triggered by the external alternative magnetic field was monitored by an implanted microdialysis perfusion probe with an on-line laser-induced fluorescence detector. In the future such a device could be applied to simultaneous magnetic resonance imaging and non-invasive drug release in temperature-sensitive applications.

  3. Light-Regulated Release of Entrapped Drugs from Photoresponsive Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Kaniknun Sreejivungsa

    2016-01-01

    Full Text Available Release of a payload in a spatiotemporal fashion has a substantial impact on increasing therapeutic efficacy. In this work, a novel monolayer of gold nanoparticles (AuNPs featuring light-responsive ligands was investigated as a potential drug carrier whose drug release can be triggered by UV light. Hydrophobic molecules were noncovalently entrapped in the compartments of its monolayers. Once irradiated with UV light, the dinitrobenzyl linker was cleaved, leading to release of the entrapped agent. AuNPs were characterized using UV spectrophotometry, TEM, and a zetasizer. A naturally occurring compound extracted from Goniothalamus elegans Ast was chosen as a hydrophobic model drug. Entrapment and release of dye were monitored using fluorimetry. The percent encapsulation of dye was of 13.53%. Entrapped dye can be released upon UV irradiation and can be regulated by changing irradiation time. Up to 83.95±2.2% entrapped dye can be released after irradiation for 20 minutes. In the absence of UV light, dye release was only 19.75%. For comparison purposes, AuNPs having no dinitrobenzyl groups showed a minimal release of 12.23% and 11.69% with and without UV light, respectively. This demonstrated an alternative strategy to encapsulate drugs using a noncovalent approach followed by their controlled release upon UV irradiation.

  4. Structural changes on polymeric nanoparticles induced by hydrophobic drug entrapment

    Czech Academy of Sciences Publication Activity Database

    Jäger, Alessandro; Jäger, Eliezer; Giacomelli, F. C.; Nallet, F.; Steinhart, Miloš; Putaux, J.-L.; Konefal, Rafal; Spěváček, Jiří; Ulbrich, Karel; Štěpánek, Petr

    2018-01-01

    Roč. 538, 5 February (2018), s. 238-249 ISSN 0927-7757 R&D Projects: GA ČR(CZ) GA17-09998S; GA ČR(CZ) GA15-13853S Grant - others:AV ČR(CZ) MSM200501606 Program:Program na podporu mezinárodní spolupráce začínajících výzkumných pracovníků Institutional support: RVO:61389013 Keywords : polymer nanoparticles * drug delivery * paclitaxel Subject RIV: CD - Macromolecular Chemistry OBOR OECD: Polymer science Impact factor: 2.714, year: 2016

  5. [Depression status of academic high school students in Seoul: mediating role of entrapment].

    Science.gov (United States)

    Park, Young-Joo; Shin, Nah-Mee; Han, Kuem-Sun; Kang, Hyun-Cheol; Cheon, Sook-Hee; Shin, Hyunjeong

    2011-10-01

    Purpose of this study was to investigate the status of depression in academic high school students and path analysis model for exploring the mediating role of entrapment to depression in relation to academic stress and perceived social support. Measurements were four reliable questionnaires measuring academic stress, social support, entrapment, and depression. Data were collected from students in 17 high schools in Seoul. Students (n=5,346) completing the questionnaires indicated depression & entrapment from academic stress. Depression was more prevalent in girls, those whose parents' household income was less than two million won, who did not live with father or mother or both due to divorce, separation, or death, and those who smoked or used alcohol. Entrapment was more prevalent in students similar to cases of depression and in seniors. According to the proposed path model, 48.6% of depression was explained by academic stress, social support, and entrapment. The indirect effect of entrapment as a mediator between academic stress and depression was verified and larger than the direct effect of academic stress on depression. Considering levels of depression and entrapment demonstrated by these students, better mental health programs with diverse strategies should be developed for their psychological well-being.

  6. Enhancement of the predicted drug hepatotoxicity in gel entrapped hepatocytes within polysulfone-g-poly (ethylene glycol) modified hollow fiber

    International Nuclear Information System (INIS)

    Shen Chong; Zhang Guoliang; Meng Qin

    2010-01-01

    Collagen gel-based 3D cultures of hepatocytes have been proposed for evaluation of drug hepatotoxicity because of their more reliability than traditional monolayer culture. The collagen gel entrapment of hepatocytes in hollow fibers has been proven to well reflect the drug hepatotoxicity in vivo but was limited by adsorption of hydrophobic drugs onto hollow fibers. This study aimed to investigate the impact of hollow fibers on hepatocyte performance and drug hepatotoxicity. Polysulfone-g-poly (ethylene glycol) (PSf-g-PEG) hollow fiber was fabricated and applied for the first time to suppress the drug adsorption. Then, the impact of hollow fibers was evaluated by detecting the hepatotoxicity of eight selected drugs to gel entrapped hepatocytes within PSf and PSf-g-PEG hollow fibers, or without hollow fibers. The hepatocytes in PSf-g-PEG hollow fiber showed the highest sensitivity to drug hepatotoxicity, while those in PSf hollow fiber and cylindrical gel without hollow fiber underestimated the hepatotoxicity due to either drug adsorption or low hepatic functions. Therefore, the 3D culture of gel entrapped hepatocytes within PSf-g-PEG hollow fiber would be a promising tool for investigation of drug hepatotoxicity in vitro.

  7. Quantitative determination of insulin entrapment efficiency in triblock copolymeric nanoparticles by high-performance liquid chromatography.

    Science.gov (United States)

    Xu, Xiongliang; Fu, Yao; Hu, Haiyan; Duan, Yourong; Zhang, Zhirong

    2006-04-11

    A rapid and effective isocratic chromatographic procedure was described in this paper for the determination of insulin entrapment efficiency (EE) in triblock copolymeric nanoparticles using reversed-phase high-performance liquid chromatography (RP-HPLC) with an ultraviolet/visible detector at low flow rate. The method has been developed on a Shimadzu Shim-pack VP-ODS column (150 mm x 4.6 mm, 5 microm, Chiyoda-Ku, Tokyo, Japan) using a mixture of 0.2 M sodium sulfate anhydrous solution adjusted to pH 2.3 with phosphoric acid and acetonitrile (73:27, v/v) as mobile phase at the flow rate of 0.8 ml min(-1) and a 214 nm detection. The method was validated in terms of selectivity, linearity, precision, accuracy, solution stability, limit of detection (LOD) and limit of quantification (LOQ). The calibration curve was linear in the concentration range of 2.0-500.0 microg ml(-1), and the limits of detection and quantitation were 8 and 20 ng, respectively. The mean recovery of insulin from spiked samples, in a concentration range of 8-100 microg ml(-1), was 98.96% (R.S.D.= 2.51%, n = 9). The intra- and inter-assay coefficients of variation were less than 2.24%. The proposed method has the advantages of simple pretreatment, rapid isolation, high specificity and precision, which can be used for direct analysis of insulin in commercially available raw materials, formulations of nanoparticles, and drug release as well as stability studies.

  8. Defeat and entrapment: more than meets the eye? Applying network analysis to estimate dimensions of highly correlated constructs.

    Science.gov (United States)

    Forkmann, Thomas; Teismann, Tobias; Stenzel, Jana-Sophie; Glaesmer, Heide; de Beurs, Derek

    2018-01-25

    Defeat and entrapment have been shown to be of central relevance to the development of different disorders. However, it remains unclear whether they represent two distinct constructs or one overall latent variable. One reason for the unclarity is that traditional factor analytic techniques have trouble estimating the right number of clusters in highly correlated data. In this study, we applied a novel approach based on network analysis that can deal with correlated data to establish whether defeat and entrapment are best thought of as one or multiple constructs. Explanatory graph analysis was used to estimate the number of dimensions within the 32 items that make up the defeat and entrapment scales in two samples: an online community sample of 480 participants, and a clinical sample of 147 inpatients admitted to a psychiatric hospital after a suicidal attempt or severe suicidal crisis. Confirmatory Factor analysis (CFA) was used to test whether the proposed structure fits the data. In both samples, bootstrapped exploratory graph analysis suggested that the defeat and entrapment items belonged to different dimensions. Within the entrapment items, two separate dimensions were detected, labelled internal and external entrapment. Defeat appeared to be multifaceted only in the online sample. When comparing the CFA outcomes of the one, two, three and four factor models, the one factor model was preferred. Defeat and entrapment can be viewed as distinct, yet, highly associated constructs. Thus, although replication is needed, results are in line with theories differentiating between these two constructs.

  9. Nifedipine-loaded polymeric nanocapsules: validation of a stability-indicating HPLC method to evaluate the drug entrapment efficiency and in vitro release profiles.

    Science.gov (United States)

    Granada, Andréa; Tagliari, Monika Piazzon; Soldi, Valdir; Silva, Marcos António Segatto; Zanetti-Ramos, Betina Ghiel; Fernandes, Daniel; Stulzer, Hellen Karine

    2013-01-01

    A simple stability-indicating analytical method was developed and validated to quantify nifedipine in polymeric nanocapsule suspensions; an in vitro drug release study was then carried out. The analysis was performed using an RP C18 column, UV-Vis detection at 262 nm, and methanol-water (70 + 30, v/v) mobile phase at a flow rate of 1.2 mL/min. The method was validated in terms of specificity, linearity and range, LOQ, accuracy, precision, and robustness. The results obtained were within the acceptable ranges. The nanocapsules, made of poly(epsilon-caprolactone), were prepared by the solvent displacement technique and showed high entrapment efficiency. The entrapment efficiency was 97.6 and 98.2% for the nifedipine-loaded polymeric nanocapsules prepared from polyvinyl alcohol (PVA) and Pluronic F68 (PF68), respectively. The particle size and zeta potential of nanocapsules were found to be influenced by the nature of the stabilizer used. The mean diameter and zeta potential for nanocapsules with PVA and PF68 were 290.9 and 179.9 nm, and -17.7 mV and -32.7 mV, respectively. The two formulations prepared showed a drug release of up to 70% over 4 days. This behavior indicates the viability of this drug delivery system for use as a controlled-release system.

  10. Selective entrapment of the cationic form of norfloxacin within anionic sodium dodecyl sulfate micelles at physiological pH and its effect on the drug photodecomposition.

    Science.gov (United States)

    Sortino, Salvatore

    2006-01-01

    The binding of the photosensitizing fluoroquinolone (FQ) antibiotic norfloxacin (NX) to sodium dodecyl sulfate (SDS) micelles and the photoreactivity of the NX/SDS complex under physiological pH conditions are investigated by means of absorption and emission spectroscopy, steady-state and laser flash photolysis. It is shown that the photolabile zwitterionic form of NX, which is dominant at physiological pH, is not the most abundant species in the presence of SDS micelles. This medium exhibits a high preference for the cationic form of the drug, which is selectively and successfully entrapped within the micellar cage (K(ass) = 6 x 10(4) M(-1) +/- 3000), becoming the largely dominant species at neutral pH. The effect of this trapping is drastically reflected on both efficiency and nature of the drug photodecomposition. It is observed that the photostability of NX incorporated in the micellar pseudophase increases of more than one order of magnitude if compared to that of the "free" drug. Furthermore, the radical photodecomposition mechanism occurring in phosphate buffered solution is suppressed by the micellar medium and the low photodegradation observed seems to take place preferentially through an ionic pathway. Hopefully, the results presented herein may contribute to a better understanding of the bio-distribution of NX in biological systems and provide helpful and stimulating information in order to get the control of FQ photoreactivity under physiological pH conditions.

  11. An electrochemical and high-speed imaging study of micropore decontamination by acoustic bubble entrapment.

    Science.gov (United States)

    Offin, Douglas G; Birkin, Peter R; Leighton, Timothy G

    2014-03-14

    Electrochemical and high-speed imaging techniques are used to study the abilities of ultrasonically-activated bubbles to clean out micropores. Cylindrical pores with dimensions (diameter × depth) of 500 μm × 400 μm (aspect ratio 0.8), 125 μm × 350 μm (aspect ratio 2.8) and 50 μm × 200 μm (aspect ratio 4.0) are fabricated in glass substrates. Each pore is contaminated by filling it with an electrochemically inactive blocking organic material (thickened methyl salicylate) before the substrate is placed in a solution containing an electroactive species (Fe(CN)6(3-)). An electrode is fabricated at the base of each pore and the Faradaic current is used to monitor the decontamination as a function of time. For the largest pore, decontamination driven by ultrasound (generated by a horn type transducer) and bulk fluid flow are compared. It is shown that ultrasound is much more effective than flow alone, and that bulk fluid flow at the rates used cannot decontaminate the pore completely, but that ultrasound can. In the case of the 125 μm pore, high-speed imaging is used to elucidate the cleaning mechanisms involved in ultrasonic decontamination and reveals that acoustic bubble entrapment is a key feature. The smallest pore is used to explore the limits of decontamination and it is found that ultrasound is still effective at this size under the conditions employed.

  12. Three recent ice entrapments of Arctic cetaceans in West Greenland and the eastern Canadian High Arctic

    Directory of Open Access Journals (Sweden)

    MP Heide-Jørgensen

    2002-07-01

    Full Text Available Three ice entrapments of Monodontids have been reported in the western North Atlantic since 1993. Hunters in Disko Bay, West Greenland, discovered one in March 1994 that included about 150 narwhals (Monodon monoceros. The entrapment occurred during a sudden cold period which caused ice to form rapidly. The trapped whales were subject to hunting, but about 50 of the killed whales could not be retrieved in the ice. The whales were trapped in a small opening in the ice and because of that they would probably have succumbed even if not discovered by hunters. Two entrapments involving white whales or belugas (Delphinapterus leucas occurred in the eastern Canadian Arctic in May 1999; one in Lancaster Sound discovered by polar bear (Ursus maritimus researchers and one in Jones Sound discovered by hunters. The first included one bowhead whale (Balaena mysticetus and about 40 belugas that were being preyed upon by polar bears. The second involved at least 170 belugas, of which about 100 were killed by polar bears and 17 were taken by hunters. The entrapments in Disko Bay and Jones Sound both occurred in areas where entrapments have previously been reported, whereas the one in Lancaster Sound was in a new area.

  13. The impact of calcium carbonate as pore forming agent and drug entrapment method towards drug dissolution mechanism of amoxicillin trihydrate encapsulated by chitosan-methyl cellulose semi-IPN hydrogel for floating drug delivery system

    Science.gov (United States)

    Dewantara, Fauzi; Budianto, Emil

    2018-04-01

    Chitosan-methyl cellulose semi-IPN hydrogel is used as floating drug delivery system, and calcium carbonate also added as pore forming agent. The hydrogel network arranged by not only using biopolymer chitosan and methyl cellulose, but also the crosslink agent that is glutaraldehyde. Amoxicillin trihydrate entrapped into the polymer network with two different method, in situ loading and post loading. Furthermore both method has been tested for drug entrapment efficiency along with drug dissolution test, and the result for drug entrapment efficiency is in situ loading method has highest value of 100%, compared to post loading method which has value only 71%. Moreover, at the final time of drug dissolution test shows in situ loading method has value of 96% for total accumulative of drug dissolution, meanwhile post loading method has 72%. The value of drug dissolution test from both method is used for analyzing drug dissolution mechanism of amoxicillin trihydrate from hydrogel network with four mathematical drug mechanism models as parameter. The polymer network encounter destructive degradation causes by acid solution which used as dissolution medium, and the level of degradation is observed with optical microscope. However the result shows that degradation of the polymer network doesn't affect drug dissolution mechanism directly. Although the pore forming agent causes the pore inside the hydrogel network create interconnection and it was quite influential to drug dissolution mechanism. Interconnected pore is observed with Scanning Electron Microscope (SEM) and shows that the amount and area of interconnected pore inside the hydrogel network is increasing as drug dissolution goes on.

  14. Bubble entrapment through topological change

    KAUST Repository

    Thoroddsen, Sigurdur T.

    2010-05-03

    When a viscousdrop impacts onto a solid surface, it entraps a myriad of microbubbles at the interface between liquid and solid. We present direct high-speed video observations of this entrapment. For viscousdrops, the tip of the spreading lamella is separated from the surface and levitated on a cushion of air. We show that the primary mechanism for the bubble entrapment is contact between this precursor sheet of liquid with the solid and not air pulled directly through cusps in the contact line. The sheet makes contact with the solid surface,forming a wetted patch, which grows in size, but only entraps a bubble when it meets the advancing contact line. The leading front of this wet patch can also lead to the localized thinning and puncturing of the liquid film producing strong splashing of droplets.

  15. Bubble entrapment through topological change

    KAUST Repository

    Thoroddsen, Sigurdur T; Takehara, K.; Etoh, T. G.

    2010-01-01

    When a viscousdrop impacts onto a solid surface, it entraps a myriad of microbubbles at the interface between liquid and solid. We present direct high-speed video observations of this entrapment. For viscousdrops, the tip of the spreading lamella is separated from the surface and levitated on a cushion of air. We show that the primary mechanism for the bubble entrapment is contact between this precursor sheet of liquid with the solid and not air pulled directly through cusps in the contact line. The sheet makes contact with the solid surface,forming a wetted patch, which grows in size, but only entraps a bubble when it meets the advancing contact line. The leading front of this wet patch can also lead to the localized thinning and puncturing of the liquid film producing strong splashing of droplets.

  16. High performance electrophoresis system for site-specific entrapment of nanoparticles in a nanoarray

    Science.gov (United States)

    Han, Jin-Hee; Lakshmana, Sudheendra; Kim, Hee-Joo; Hass, Elizabeth A.; Gee, Shirley; Hammock, Bruce D.; Kennedy, Ian

    2010-02-01

    A nanoarray, integrated with an electrophoretic system, was developed to trap nanoparticles into their corresponding nanowells. This nanoarray overcomes the complications of losing the function and activity of the protein binding to the surface in conventional microarrays by using minimum amounts of sample. The nanoarray is also superior to other biosensors that use immunoassays in terms of lowering the limit of detection to the femto- or atto-molar level. In addition, our electrophoretic particle entrapment system (EPES) is able to effectively trap the nanoparticles using a low trapping force for a short duration. Therefore, good conditions for biological samples conjugated with particles can be maintained. The channels were patterned onto a bi-layer consisting of a PMMA and LOL coating on conductive indium tin oxide (ITO)-coated glass slide by using e-beam lithography. The suspensions of 170 nm-nanoparticles then were added to the chip that was connected to a positive voltage. On top of the droplet, another ITO-coated-glass slide was covered and connected to a ground terminal. Negatively charged fluorescent nanoparticles (blue emission) were selectively trapped onto the ITO surface at the bottom of the wells by following electric field lines. Numerical modeling was performed by using commercially available software, COMSOL Multiphysics to provide better understanding about the phenomenon of electrophoresis in a nanoarray. Simulation results are also useful for optimally designing a nanoarray for practical applications.

  17. Entrapment of ovalbumin into liposomes--factors affecting entrapment efficiency, liposome size, and zeta potential.

    Science.gov (United States)

    Brgles, Marija; Jurasin, Darija; Sikirić, Maja Dutour; Frkanec, Ruza; Tomasić, Jelka

    2008-01-01

    Various amounts of Ovalbumin (OVA) were encapsulated into positively and negatively charged multilamellar liposomes, with the aim to investigate the entrapment efficiency in different buffers and to study their effects on the liposome size and zeta potential. Results showed that the entrapment efficiency of OVA in anionic liposomes was the same in 10 mM Phosphate Buffer (PB) as in Phosphate-Buffered Saline (PBS; PB + 0.15 M NaCl). Also, liposome size was approximately 1200 nm for all anionic liposomes incorporating OVA. The entrapment efficiency of OVA in cationic liposomes was highly dependent on ionic strength. The size of cationic liposomes was approximately 1200 nm in PBS, regardless of protein content, but increased with the amount of the incorporated protein in PB. Aggregation of cationic liposomes in PB was observed when the mass of the protein was 2.5 mg or greater. The zeta potential of anionic liposomes was negative and of cationic liposomes positive in the whole range of protein mass tested. These results show how different compositions of lipid and aqueous phases can be used to vary the entrapment efficiency, liposome size, and zeta potential--the factors that are of great importance for the use of liposomes as drug carriers.

  18. High-Resolution Experimental Investigation of mass transfer enhancement by chemical oxidation from DNAPL entrapped in variable-aperture fractures

    Science.gov (United States)

    Arshadi, M.; Rajaram, H.; Detwiler, R. L.; Jones, T.

    2012-12-01

    Permanganate oxidation of DNAPL- contaminated fractured rock is an effective remediation technology. Permanganate ion reacts with dissolved DNAPL in a bi-molecular oxidation-reduction reaction. The consumption of dissolved DNAPL in this reaction results in increased concentration gradients away from the free-phase DNAPL, resulting in reaction-enhanced mass transfer, which accelerates contaminant removal. The specific objective of our research was to perform high-resolution non-intrusive experimental studies of permanganate oxidation in a 15.24 × 15.24 cm, transparent, analog, variable-aperture fracture with complex initial TCE entrapped phase geometry. Our experimental system uses light-transmission techniques to accurately measure both fracture aperture and the evolution of individual entrapped DNAPL blobs during the remediation experiments at high resolution (pixel size : 6.2×10-3 cm). Three experiments were performed with different flow rates and permanganate inflow concentrations to observe DNAPL-permanganate interactions across a broader range of conditions. Prior to initiating each experiment, the aperture field within the fracture was measured. The oxidation experiment was initiated by TCE injection into the water saturated fracture till the TCE reached the outflow end, followed by water re-injection through the fracture. The flowing water mobilized some TCE. We continued injection of water till TCE mobilization ceased, leaving behind the residual TCE entrapped within the variable-aperture fracture. Subsequently, permanganate injection through the fracture resulted in propagation of a fingered reaction front into the fracture. We developed image processing algorithms to analyze the evolution of DNAPL phase geometry over the duration of the experiment. The permanganate consumption rate varied significantly within the fracture due to the complex flow and DNAPL concentration fields. Precipitated MnO2 was clearly evident on the downstream side of DNAPL blobs

  19. MAGNOLOL ENTRAPPED ULTRA-FINE FIBROUS MATS ELECTROSPUN FROM POLY(ETHYLENE GLYCOL)-b-POLY(L-LACTIDE) AND IN VITRO RELEASE

    Institute of Scientific and Technical Information of China (English)

    Hao Wang; Hong-rui Song; Yong Cui; Ying-jie Deng; Xue-si Chen

    2011-01-01

    Ultra-fine fibrous mats with magnolol entrapped have been prepared by electrospinning biodegradable copolymer poly(ethylene glycol) blocked poly(L-lactide). Drug entrapment was perfect which was confirmed by scanning electron microscopy and differential scanning calorimetry. According to in vitro drug release investigation by high performance liquid chromatography, it was found that fibers with 10%, 20% and 30% drug entrapped respect to polymer (mass ratio) presented dramatically different drug release behavior and degradation behavior under the effect of proteinase K. The reason may be that fibers with 10% drug entrapped was more easily affected by enzyme while, to some degree, magnolol in fibers with 20% and 30% entrapped prevented polymer from being degraded by enzyme.

  20. Preparation of non-porous microspheres with high entrapment efficiency of proteins by a (water-in-oil)-in-oil emulsion technique.

    Science.gov (United States)

    Viswanathan, N B; Thomas, P A; Pandit, J K; Kulkarni, M G; Mashelkar, R A

    1999-03-08

    Emulsification-solvent removal methods have been widely used for encapsulating bioactive macromolecules like proteins and polypeptides in biodegradable polymers. We report, a (water-in-oil)-in-oil emulsion technique wherein proteins and polypeptides differing in molecular weight and shape were encapsulated in polymers of current biomedical interest. When an oil was used as the processing medium in combination with a carefully selected mixed solvent system such that a stable (w/o1/o2 emulsion is formed and solvents are removed by a combination of extraction and evaporation, the entrapment efficiency was high and the product nonporous. The entrapment efficiency of globular proteins exceeded 90% while that of fibrous proteins was around 70%. Fracture studies revealed that the polymer matrix was dense. The mechanism of entrapment involved solvent-induced precipitation of the protein as the microspheres were being formed. The principle of the method will find use in preparation of non-porous polymer microparticles with reduced burst effect.

  1. Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.

    Science.gov (United States)

    Hanafy, Amira S; Farid, Ragwa M; ElGamal, Safaa S

    2015-01-01

    Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully

  2. The moderating effects of coping and self-esteem on the relationship between defeat, entrapment and suicidality in a sample of prisoners at high risk of suicide.

    Science.gov (United States)

    Gooding, P; Tarrier, N; Dunn, G; Shaw, J; Awenat, Y; Ulph, F; Pratt, D

    2015-11-01

    Research is sparse which examines pathways to suicide, and resilience to suicide, in people who are particularly vulnerable to suicide, for example, prison inmates. The purpose of this study was to examine the ways in which perceptions of self-esteem and coping ability interacted with defeat and entrapment to both amplify suicidal thoughts and feelings, and to act as a buffer against suicidal thoughts and feelings. Participants were 65 male prisoners at high risk of suicide. A cross-sectional questionnaire design was used. Questionnaire measures of depression, defeat, entrapment, self-esteem, coping ability and suicidal probability were administered. For the hopelessness component of the suicide probability measure, high levels of coping ability together with low levels of defeat resulted in the lowest levels of suicidality indicative of a resilience factor. In contrast, low levels of coping skills together with high levels of entrapment were a high risk factor for this hopelessness component of suicide. This pattern of results pertained when controlling for depression levels. This is the first study to examine interactions between defeat, entrapment and appraisals of self-esteem and coping ability. Therapeutic interventions would benefit from boosting perceptions and appraisals of coping ability, in particular, in people who are at high risk for suicide. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  3. Diclofenac sodium entrapment and release from halloysite nanotubules.

    Science.gov (United States)

    Krejčová, Kateřina; Deasy, Patrick B; Rabišková, Miloslava

    2013-02-01

    Halloysite was found to have interesting nanotubular geometry viable for the entrapment of various active agents. In this experiment, the ability of hollow halloysite cylinders to entrap the anionic model drug diclofenac sodium and to retard drug dissolution rate was investigated. Drugs could be incorporated into layered tubules via three different mechanisms: adsorption, intercalation and tubular entrapment. Based on the adsorption studies, some diclofenac sodium was shown to be adsorbed to the polyionic mineral surface despite its permanent negative charge. The X-ray powder diffraction analysis (XRPD) results did not prove any intercalation reaction to occur. The most important drug-loading mechanism involved the tubular entrapment with encapsulation efficiency 48.1%. The drug release from halloysite was prolonged in comparison with the dissolution of pure drug. Halloysite itself as well as halloysite loaded with the drug proved to be appropriate material to form pellets by extrusion /spheronization method. halloysite diclofenac sodium drug entrapment pellets prolonged drug release.

  4. Studies on entrapping of enzymes and drugs in matrices by radiation-induced polymerization at low temperatures and their capabilities

    International Nuclear Information System (INIS)

    Yoshida, Masaru

    1980-03-01

    The author has studied a immobilization method for enzymes and drugs by means of radiation-induced polymerization at low temperatures in a supercooled state using glass-forming monomers. The proposed technique using glass-forming monomer has features as follows. (1) Inactivation of the bio-component by heat and radiation is almost eliminated due to the low temperature treatment. (2) Moulding or shaping of the mixture of monomer and bio-component in difference forms and sizes of polymerized composite is easy due to high viscosity of the supercooled monomer. (3) The carrier matrix may be selected from a wide range of hydrophilic and hydrophobic vinyl monomers and polymers. (4) No impurities such as a polymerization catalyst are introduced in the system. (5) A bio-component can be easily distributed in high stability, either concentrated on surface of the monomer or homogeneously within the monomer, due to large viscosity of the monomer. Furthermore, the author attempted practical usage of the technique in such as enzyme fixation for long continuous or repeated application (PART I) and controlled slow release of medicine in efficient and durable without secondary reaction (PART II). (author)

  5. Radiation cross-linked carboxymethyl sago pulp hydrogels loaded with ciprofloxacin: Influence of irradiation on gel fraction, entrapped drug and in vitro release

    International Nuclear Information System (INIS)

    Lam, Yi Lyn; Muniyandy, Saravanan; Kamaruddin, Hashim; Mansor, Ahmad; Janarthanan, Pushpamalar

    2015-01-01

    Carboxymethyl sago pulp (CMSP) with 0.4 DS, viscosity 184 dl/g and molecular weight 76,000 g/mol was synthesized from sago waste. 10 and 20% w/v solutions of CMSP were irradiated at 10–30 kGy to form hydrogels and were characterized by % gel fraction (GF). Irradiation of 20% CMSP using 25 kGy has produced stable hydrogels with the highest % GF and hence loaded with ciprofloxacin HCl. Drug-loaded hydrogels were produced by irradiating the mixture of drug and 20% CMSP solution at 25 kGy. After irradiation, the hydrogels were cut into circular discs with a diameter of 6±1 mm and evaluated for physicochemical properties as well as drug release kinetics. The ciprofloxacin loading in the disc was 14.7%±1 w/w with an entrapment efficiency of 73.5% w/w. The low standard deviation of drug-loaded discs indicated uniform thickness (1.5±0.3 mm). The unloaded discs were thinner (1±0.4 mm) and more brittle than the drug-loaded discs. FESEM, FT-IR, XRD, DSC and TGA analysis revealed the absence of polymer–drug interaction and transformation of crystalline to amorphous form of ciprofloxacin in the discs. The disc sustained the drug release in phosphate buffer pH 7.4 over 36 h in a first-order manner. The mechanism of the drug release was found to be swelling controlled diffusion and matrix erosion. The anti-bacterial effect of ciprofloxacin was retained after irradiation and CMSP disc could be a promising device for ocular drug delivery. - Highlights: • Carboxymethyl sago pulp (CMSP) with ciprofloxacin is irradiated to form hydrogels. • 20% CMSP at 25 kGy has produced stable hydrogels with the highest gel fraction. • Crystalline ciprofloxacin converted as amorphous during hydrogel formation. • Hydrogel in disc form sustained the drug release drug up to 36 h. • Irradiation cross-linked polymeric chain of CMSP resulted in controlled swelling

  6. O-hexadecyl-dextran entrapped berberine nanoparticles abrogate high glucose stress induced apoptosis in primary rat hepatocytes.

    Directory of Open Access Journals (Sweden)

    Radhika Kapoor

    Full Text Available Nanotized phytochemicals are being explored by researchers for promoting their uptake and effectiveness at lower concentrations. In this study, O-hexadecyl-dextran entrapped berberine chloride nanoparticles (BC-HDD NPs were prepared, and evaluated for their cytoprotective efficacy in high glucose stressed primary hepatocytes and the results obtained compared with bulk berberine chloride (BBR treatment. The nanotized formulation treated primary hepatocytes that were exposed to high glucose (40 mM, showed increased viability compared to the bulk BBR treated cells. BC-HDD NPs reduced the ROS generation by ∼ 3.5 fold during co-treatment, prevented GSH depletion by ∼ 1.6 fold, reduced NO formation by ∼ 5 fold and significantly prevented decline in SOD activity in stressed cells. Lipid peroxidation was also prevented by ∼ 1.9 fold in the presence of these NPs confirming the antioxidant capacity of the formulation. High glucose stress increased Bax/Bcl2 ratio followed by mitochondrial depolarization and activation of caspase-9/-3 confirming involvement of mitochondrial pathway of apoptosis in the exposed cells. Co- and post-treatment of BC-HDD NPs prevented depolarization of mitochondrial membrane, reduced Bax/Bcl2 ratio and prevented externalization of phosphatidyl-serine confirming their anti-apoptotic capacity in those cells. Sub-G1 phase apparent in high glucose stressed cells was not seen in BC-HDD NPs treated cells. The present study reveals that BC-HDD NPs at ∼ 20 fold lower concentration are as effective as BBR in preventing high glucose induced oxidative stress, mitochondrial depolarization and downstream events of apoptotic cell death.

  7. Defeat and entrapment: more than meets the eye? Applying network analysis to estimate dimensions of highly correlated constructs.

    NARCIS (Netherlands)

    Forkmann, T.; Teismann, T.; Stenzel, J.S.; Glaesmer, H.; Beurs, D. de

    2018-01-01

    Background: Defeat and entrapment have been shown to be of central relevance to the development of different disorders. However, it remains unclear whether they represent two distinct constructs or one overall latent variable. One reason for the unclarity is that traditional factor analytic

  8. The moderating effects of coping and self-esteem on the relationship between defeat, entrapment and suicidality in a sample of prisoners at high risk of suicide

    OpenAIRE

    Gooding, P.; Tarrier, N.; Dunn, G.; Shaw, J.; Awenat, Y.; Ulph, F.; Pratt, D.

    2015-01-01

    BACKGROUND: Research is sparse which examines pathways to suicide, and resilience to suicide, in people who are particularly vulnerable to suicide, for example, prison inmates. The purpose of this study was to examine the ways in which perceptions of self-esteem and coping ability interacted with defeat and entrapment to both amplify suicidal thoughts and feelings, and to act as a buffer against suicidal thoughts and feelings. METHODS: Participants were 65 male prisoners at high risk of suici...

  9. Popliteal artery entrapment syndrome

    International Nuclear Information System (INIS)

    Klooster, N.J.J.; Janevski, B.K.; Kitslaar, P.

    1988-01-01

    Two patients with unilateral popliteal artery entrapment syndrome (PAES) are reported. The importance of diligence in angiographic diagnosis and recognition of the so-called 'functional' PAES group as a separate entity are stressed. It is inferred from our material that a surgical approach for PAES is to be advocated since surgical release of the entrapment can lead to complete resolution of symptoms regardless of aetiology. (orig.) [de

  10. Popliteal artery entrapment syndrome.

    LENUS (Irish Health Repository)

    O'Leary, D P

    2010-01-01

    Popliteal artery entrapment syndrome is a rare abnormality of the anatomical relationship between the popliteal artery and adjacent muscles or fibrous bands in the popliteal fossa. The following is a case report of a 19 year old female, in whom popliteal artery entrapment syndrome was diagnosed, and successfully treated surgically. A review of literature is also presented and provides details on how PAES is classified, diagnosed both clinically and radiologically, and treated surgically.

  11. Development of a new generation of waste form for entrapment and immobilization of highly volatile and soluble radionuclides.

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez, Mark Andrew; Bencoe, Denise Nora; Brinker, C. Jeffrey; Murphy, Andrew Wilson; Holt, Kathleen Caroline; Turnham, Rigney; Kruichak, Jessica Nicole; Tellez, Hernesto; Miller, Andy; Xiong, Yongliang; Pohl, Phillip Isabio; Ockwig, Nathan W.; Wang, Yifeng; Gao, Huizhen

    2010-09-01

    The United States is now re-assessing its nuclear waste disposal policy and re-evaluating the option of moving away from the current once-through open fuel cycle to a closed fuel cycle. In a closed fuel cycle, used fuels will be reprocessed and useful components such as uranium or transuranics will be recovered for reuse. During this process, a variety of waste streams will be generated. Immobilizing these waste streams into appropriate waste forms for either interim storage or long-term disposal is technically challenging. Highly volatile or soluble radionuclides such as iodine ({sup 129}I) and technetium ({sup 99}Tc) are particularly problematic, because both have long half-lives and can exist as gaseous or anionic species that are highly soluble and poorly sorbed by natural materials. Under the support of Sandia National Laboratories (SNL) Laboratory-Directed Research & Development (LDRD), we have developed a suite of inorganic nanocomposite materials (SNL-NCP) that can effectively entrap various radionuclides, especially for {sup 129}I and {sup 99}Tc. In particular, these materials have high sorption capabilities for iodine gas. After the sorption of radionuclides, these materials can be directly converted into nanostructured waste forms. This new generation of waste forms incorporates radionuclides as nano-scale inclusions in a host matrix and thus effectively relaxes the constraint of crystal structure on waste loadings. Therefore, the new waste forms have an unprecedented flexibility to accommodate a wide range of radionuclides with high waste loadings and low leaching rates. Specifically, we have developed a general route for synthesizing nanoporous metal oxides from inexpensive inorganic precursors. More than 300 materials have been synthesized and characterized with x-ray diffraction (XRD), BET surface area measurements, and transmission electron microscope (TEM). The sorption capabilities of the synthesized materials have been quantified by using stable

  12. Development of a new generation of waste form for entrapment and immobilization of highly volatile and soluble radionuclides

    International Nuclear Information System (INIS)

    Rodriguez, Mark Andrew; Bencoe, Denise Nora; Brinker, C. Jeffrey; Murphy, Andrew Wilson; Holt, Kathleen Caroline; Turnham, Rigney; Kruichak, Jessica Nicole; Tellez, Hernesto; Miller, Andy; Xiong, Yongliang; Pohl, Phillip Isabio; Ockwig, Nathan W.; Wang, Yifeng; Gao, Huizhen

    2010-01-01

    The United States is now re-assessing its nuclear waste disposal policy and re-evaluating the option of moving away from the current once-through open fuel cycle to a closed fuel cycle. In a closed fuel cycle, used fuels will be reprocessed and useful components such as uranium or transuranics will be recovered for reuse. During this process, a variety of waste streams will be generated. Immobilizing these waste streams into appropriate waste forms for either interim storage or long-term disposal is technically challenging. Highly volatile or soluble radionuclides such as iodine ( 129 I) and technetium ( 99 Tc) are particularly problematic, because both have long half-lives and can exist as gaseous or anionic species that are highly soluble and poorly sorbed by natural materials. Under the support of Sandia National Laboratories (SNL) Laboratory-Directed Research and Development (LDRD), we have developed a suite of inorganic nanocomposite materials (SNL-NCP) that can effectively entrap various radionuclides, especially for 129 I and 99 Tc. In particular, these materials have high sorption capabilities for iodine gas. After the sorption of radionuclides, these materials can be directly converted into nanostructured waste forms. This new generation of waste forms incorporates radionuclides as nano-scale inclusions in a host matrix and thus effectively relaxes the constraint of crystal structure on waste loadings. Therefore, the new waste forms have an unprecedented flexibility to accommodate a wide range of radionuclides with high waste loadings and low leaching rates. Specifically, we have developed a general route for synthesizing nanoporous metal oxides from inexpensive inorganic precursors. More than 300 materials have been synthesized and characterized with x-ray diffraction (XRD), BET surface area measurements, and transmission electron microscope (TEM). The sorption capabilities of the synthesized materials have been quantified by using stable isotopes I and

  13. Gel entrapment culture of rat hepatocytes for investigation of tetracycline-induced toxicity

    International Nuclear Information System (INIS)

    Shen Chong; Meng Qin; Schmelzer, Eva; Bader, Augustinus

    2009-01-01

    This paper aimed to explore three-dimensionally cultured hepatocytes for testing drug-induced nonalcoholic steatohepatitis. Gel entrapped rat hepatocytes were applied for investigation of the tetracycline-induced steatohepatitis, while hepatocyte monolayer was set as a control. The toxic responses of hepatocytes were systematically evaluated by measuring cell viability, liver-specific function, lipid accumulation, oxidative stress, adenosine triphosphate content and mitochondrial membrane potential. The results suggested that gel entrapped hepatocytes showed cell death after 96 h of tetracycline treatment at 25 μM which is equivalent to toxic serum concentration in rats, while hepatocyte monolayer showed cell death at a high dose of 200 μM. The concentration-dependent accumulation of lipid as well as mitochondrial damage were regarded as two early events for tetracycline hepatotoxicity in gel entrapment culture due to their detectability ahead of subsequent increase of oxidative stress and a final cell death. Furthermore, the potent protection of fenofibrate and fructose-1,6-diphosphate were evidenced in only gel entrapment culture with higher expressions on the genes related to β-oxidation than hepatocyte monolayer, suggesting the mediation of lipid metabolism and mitochondrial damage in tetracycline toxicity. Overall, gel entrapped hepatocytes in three-dimension reflected more of the tetracycline toxicity in vivo than hepatocyte monolayer and thus was suggested as a more relevant system for evaluating steatogenic drugs.

  14. Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant Mycobacterium Tuberculosis.

    Science.gov (United States)

    Upadhyay, Seema; Khan, Iliyas; Gothwal, Avinash; Pachouri, Praveen K; Bhaskar, N; Gupta, Umesh D; Chauhan, Devendra S; Gupta, Umesh

    2017-09-01

    First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF. HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and 1 H-NMR spectroscopy. Later on RIF loaded HPMA-PLA-INH co-polymeric micelles (PMRI) were formulated and characterized for size, zeta potential and surface morphology (SEM, TEM) as well as critical micellar concentration. The safety was assessed through RBC's interaction study. The prepared PMRI were evaluated through MABA assay against sensitive and resistant strains of M. Tuberculosis. Size, zeta and entrapment efficiency for RIF loaded HPMA-PLA-INH polymeric micelles (PMRI) was 87.64 ± 1.98 nm, -19 ± 1.93 mV and 97.2 ± 1.56%, respectively. In vitro release followed controlled and sustained delivery pattern. Sustained release was also supported by release kinetics. Haemolytic toxicity of HPI and PMRI was 8.57 and 7.05% (p PLA polymeric micelles (PMRI) were more effective against sensitive and resistant M tuberculosis. The developed approach can lead to improved patient compliance and reduced dosing in future, offering improved treatment of tuberculosis.

  15. Drop impact entrapment of bubble rings

    KAUST Repository

    Thoraval, M.-J.; Takehara, K.; Etoh, T.G.; Thoroddsen, Sigurdur T

    2013-01-01

    We use ultra-high-speed video imaging to look at the initial contact of a drop impacting on a liquid layer. We observe experimentally the vortex street and the bubble-ring entrapments predicted numerically, for high impact velocities, by Thoraval et

  16. Bubble entrapment during sphere impact onto quiescent liquid surfaces

    KAUST Repository

    Marston, Jeremy; Vakarelski, Ivan Uriev; Thoroddsen, Sigurdur T

    2011-01-01

    We report observations of air bubble entrapment when a solid sphere impacts a quiescent liquid surface. Using high-speed imaging, we show that a small amount of air is entrapped at the bottom tip of the impacting sphere. This phenomenon is examined

  17. MR imaging evaluation of suprascapular nerve entrapment

    International Nuclear Information System (INIS)

    Ludig, T.; Walter, F.; Roland, J.; Blum, A.; Chapuis, D.; Mole, D.

    2001-01-01

    The aim of this study was to assess the significance of muscular edema, atrophy, and fatty changes in the diagnosis of suprascapular nerve entrapment (SSNE), and to confirm muscular edema as the most significant sign of neuropathy. A retrospective study of 18 patients with suprascapular nerve entrapment was performed. All patients underwent electromyographic studies and MR imaging with a 1.5-T Echo Speed system (General Electric, Milwaukee, Wis.). The diagnosis of muscle edema was reached when muscles presented a high signal on T2-weighted fast spin-echo (SE) fat-suppressed images. Muscular trophicity and fatty changes were analyzed on a sagittal oblique cut using SE T1-weighted images. Intra- and inter-observer reproducibility using kappa test, sensitivity, and specificity were analyzed, together with negative and positive predictive value of each criterion. The topographic diagnosis was correct as edema affected the infraspinatus muscle alone when the suprascapular nerve was entrapped at the spinoglenoid notch. Both the supraspinatus and infraspinatus muscles were affected when nerve was compressed at the suprascapular notch. Sensitivity and specificity of muscular edema were, respectively, 94.5 and 100%. Muscular atrophy sensitivity and specificity were 81 and 80%, respectively. Fatty changes sensitivity and specificity were 25 and 96%, respectively. Muscular edema seems to be a more sensitive sign of SSNE than muscle atrophy and fatty changes when compared with EMG results. Magnetic resonance imaging can reach a positive, topographic, and etiologic diagnosis of SSNE. (orig.)

  18. Resveratrol-Loaded Polymeric Nanoparticles: Validation of an HPLC-PDA Method to Determine the Drug Entrapment and Evaluation of Its Antioxidant Activity

    OpenAIRE

    da Rocha Lindner, Gabriela; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2013-01-01

    Poly(lactic acid) (PLA) and PLA-poly(ethylene glycol) (PLA-PEG) nanoparticles containing resveratrol (RVT) were developed, and their antioxidant activity was evaluated. An analytical method using high performance liquid chromatography (HPLC)/photodiode array (PDA) detection was also developed and validated for RVT determination in nanoparticles. The mobile phase consisted of methanol : water (51 : 49, v/v) flowed at 0.9 mL/min, and the PDA detector was set at wavelength of 306 nm. The mean di...

  19. Resveratrol-loaded polymeric nanoparticles: validation of an HPLC-PDA method to determine the drug entrapment and evaluation of its antioxidant activity.

    Science.gov (United States)

    da Rocha Lindner, Gabriela; Khalil, Najeh Maissar; Mainardes, Rubiana Mara

    2013-01-01

    Poly(lactic acid) (PLA) and PLA-poly(ethylene glycol) (PLA-PEG) nanoparticles containing resveratrol (RVT) were developed, and their antioxidant activity was evaluated. An analytical method using high performance liquid chromatography (HPLC)/photodiode array (PDA) detection was also developed and validated for RVT determination in nanoparticles. The mobile phase consisted of methanol : water (51 : 49, v/v) flowed at 0.9 mL/min, and the PDA detector was set at wavelength of 306 nm. The mean diameter of the nanoparticles varied between 180 and 220 nm, and the encapsulation efficiency of RVT ranged from 60% to 88%. The nanoparticles containing RVT were evaluated for their ability to scavenge the radical (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) (ABTS•⁺). The profile obtained from the PLA nanoparticles containing RVT demonstrated that after 24 h, there was almost no increase in antioxidant activity, which was lower than that of the free RVT and RVT-loaded PLA-PEG nanoparticles. For PLA-PEG nanoparticles, the radical-scavenging activity of RVT was shown to increase with time, and after 48 h, it was similar to that observed with free RVT.

  20. Resveratrol-Loaded Polymeric Nanoparticles: Validation of an HPLC-PDA Method to Determine the Drug Entrapment and Evaluation of Its Antioxidant Activity

    Directory of Open Access Journals (Sweden)

    Gabriela da Rocha Lindner

    2013-01-01

    Full Text Available Poly(lactic acid (PLA and PLA-poly(ethylene glycol (PLA-PEG nanoparticles containing resveratrol (RVT were developed, and their antioxidant activity was evaluated. An analytical method using high performance liquid chromatography (HPLC/photodiode array (PDA detection was also developed and validated for RVT determination in nanoparticles. The mobile phase consisted of methanol : water (51 : 49, v/v flowed at 0.9 mL/min, and the PDA detector was set at wavelength of 306 nm. The mean diameter of the nanoparticles varied between 180 and 220 nm, and the encapsulation efficiency of RVT ranged from 60% to 88%. The nanoparticles containing RVT were evaluated for their ability to scavenge the radical (2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid diammonium salt (ABTS•+. The profile obtained from the PLA nanoparticles containing RVT demonstrated that after 24 h, there was almost no increase in antioxidant activity, which was lower than that of the free RVT and RVT-loaded PLA-PEG nanoparticles. For PLA-PEG nanoparticles, the radical-scavenging activity of RVT was shown to increase with time, and after 48 h, it was similar to that observed with free RVT.

  1. A novel drug delivery gel of terbinafine hydrochloride with high penetration for external use.

    Science.gov (United States)

    Yang, Yan; Ou, Rujing; Guan, Shixia; Ye, Xiaoling; Hu, Bo; Zhang, Yi; Lu, Shufan; Zhou, Yubin; Yuan, Zhongwen; Zhang, Jun; Li, Qing-Guo

    2015-12-01

    Terbinafine hydrochloride is an antifungal drug for onychomycosis. Poor permeability of its external preparation leads to poor curative effect. Transfersomes, also known as flexible liposome, could improve transmission of drug for local external use. Terbinafine hydrochloride-loaded liposome is expected to become a breakthrough on the treatment of onychomycosis. This study is aimed to prepare high skin penetration terbinafine hydrochloride transfersomes with high encapsulation efficiency, appropriate drug loading and good stability. Taking entrapment efficiency as the main indicator, the formulations and the processes of preparation were investigated. Transfersomes with different surfactants were prepared in the optimization processes, and the formulations were optimized through the transdermal test in vitro. As a result, a gel contained transfersomes was obtained with a brief evaluation. Its pharmacokinetic properties of going through the skin were studied by using the micro dialysis technology and liquid chromatography-mass spectrometry to assay the penetration behavior of terbinafine. Mean particle size of the terbinafine hydrochloride transfersomes was 69.6 ± 1.23 nm, and the entrapment efficiency was 95.4% ± 0.51. The content of the gel was 4.45 ± 0.15 mg/g. The accumulated permeation of the transfersomes gel in 12 h was 88.52 ± 4.06 µg cm -2 and the intracutaneous drug detention was 94.38 ± 5.26 µg cm -2 . The results of pharmacokinetic studies showed the C max and area under the curve (AUC) were apparently higher than the commercial cream. The terbinafine hydrochloride transfersomes was highly absorbed by the skin. The absorption rate was significantly higher than that of the commercial cream either in the transdermal test in vitro or in the pharmacokinetic studies in vivo.

  2. [A model list of high risk drugs].

    Science.gov (United States)

    Cotrina Luque, J; Guerrero Aznar, M D; Alvarez del Vayo Benito, C; Jimenez Mesa, E; Guzman Laura, K P; Fernández Fernández, L

    2013-12-01

    «High-risk drugs» are those that have a very high «risk» of causing death or serious injury if an error occurs during its use. The Institute for Safe Medication Practices (ISMP) has prepared a high-risk drugs list applicable to the general population (with no differences between the pediatric and adult population). Thus, there is a lack of information for the pediatric population. The main objective of this work is to develop a high-risk drug list adapted to the neonatal or pediatric population as a reference model for the pediatric hospital health workforce. We made a literature search in May 2012 to identify any published lists or references in relation to pediatric and/or neonatal high-risk drugs. A total of 15 studies were found, from which 9 were selected. A model list was developed mainly based on the ISMP one, adding strongly perceived pediatric risk drugs and removing those where the pediatric use was anecdotal. There is no published list that suits pediatric risk management. The list of pediatric and neonatal high-risk drugs presented here could be a «reference list of high-risk drugs » for pediatric hospitals. Using this list and training will help to prevent medication errors in each drug supply chain (prescribing, transcribing, dispensing and administration). Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  3. Nasal Delivery of High Molecular Weight Drugs

    Directory of Open Access Journals (Sweden)

    Erdal Cevher

    2009-09-01

    Full Text Available Nasal drug delivery may be used for either local or systemic effects. Low molecular weight drugs with are rapidly absorbed through nasal mucosa. The main reasons for this are the high permeability, fairly wide absorption area, porous and thin endothelial basement membrane of the nasal epithelium. Despite the many advantages of the nasal route, limitations such as the high molecular weight (HMW of drugs may impede drug absorption through the nasal mucosa. Recent studies have focused particularly on the nasal application of HMW therapeutic agents such as peptide-protein drugs and vaccines intended for systemic effects. Due to their hydrophilic structure, the nasal bioavailability of peptide and protein drugs is normally less than 1%. Besides their weak mucosal membrane permeability and enzymatic degradation in nasal mucosa, these drugs are rapidly cleared from the nasal cavity after administration because of mucociliary clearance. There are many approaches for increasing the residence time of drug formulations in the nasal cavity resulting in enhanced drug absorption. In this review article, nasal route and transport mechanisms across the nasal mucosa will be briefly presented. In the second part, current studies regarding the nasal application of macromolecular drugs and vaccines with nanoand micro-particulate carrier systems will be summarised.

  4. Drop impact entrapment of bubble rings

    KAUST Repository

    Thoraval, M.-J.

    2013-04-29

    We use ultra-high-speed video imaging to look at the initial contact of a drop impacting on a liquid layer. We observe experimentally the vortex street and the bubble-ring entrapments predicted numerically, for high impact velocities, by Thoraval et al. (Phys. Rev. Lett., vol. 108, 2012, article 264506). These dynamics mainly occur within 50 -s after the first contact, requiring imaging at 1 million f.p.s. For a water drop impacting on a thin layer of water, the entrapment of isolated bubbles starts through azimuthal instability, which forms at low impact velocities, in the neck connecting the drop and pool. For Reynolds number Re above -12 000, up to 10 partial bubble rings have been observed at the base of the ejecta, starting when the contact is -20% of the drop size. More regular bubble rings are observed for a pool of ethanol or methanol. The video imaging shows rotation around some of these air cylinders, which can temporarily delay their breakup into micro-bubbles. The different refractive index in the pool liquid reveals the destabilization of the vortices and the formation of streamwise vortices and intricate vortex tangles. Fine-scale axisymmetry is thereby destroyed. We show also that the shape of the drop has a strong influence on these dynamics. 2013 Cambridge University Press.

  5. Medical image of the week: lung entrapment

    Directory of Open Access Journals (Sweden)

    Natt B

    2016-07-01

    Full Text Available No abstract available. Article truncated at 150 words. A 74-year-old woman with a history of breast cancer 10 years ago treated with lumpectomy and radiation presented for evaluation of shortness of breath. She was diagnosed with left sided pleural effusion which was recurrent requiring multiple thoracenteses. There was increased pleural fludeoxyglucose (FDG uptake on PET-CT indicative of recurrent metastatic disease. She underwent a medical pleuroscopy since the pleural effusion analysis did not reveal malignant cells although the suspicion was high and tunneled pleural catheter placement as adjuvant chemotherapy was initiated. Figure 1 shows a pleurscopic view of the collapsed left lung and the effusion in the left hemi thorax. Figure 2 shows extensive involvement of the visceral pleura with metastatic disease preventing complete lung inflation. Figure 3 shows persistent pneumothorax-ex-vacuo despite pleural catheter placement confirming the diagnosis of entrapment. Incomplete lung inflation can be due to pleural disease, endobronchial lesions or chronic telecasts. Lung entrapment and trapped lung ...

  6. Ulnar nerve entrapment by anconeus epitrochlearis ligament.

    LENUS (Irish Health Repository)

    Tiong, William H C

    2012-01-01

    Ulnar nerve entrapment at the elbow is the second most common upper limb entrapment neuropathy other than carpal tunnel syndrome. There have been many causes identified ranging from chronic aging joint changes to inflammatory conditions or systemic disorders. Among them, uncommon anatomical variants accounts for a small number of cases. Here, we report our experience in managing ulnar nerve entrapment caused by a rare vestigial structure, anconeus epitrochlearis ligament, and provide a brief review of the literature of its management.

  7. Air entrapment in piezo-driven inkjet printheads

    NARCIS (Netherlands)

    de Jong, J.; de Bruin, G.J.; de Bruin, Gerrit; Reinten, Hans; van den Berg, Marc; Wijshoff, Herman; Wijshoff, H.; Versluis, Michel; Lohse, Detlef

    2006-01-01

    The stability of inkjet printers is a major requirement for high-quality-printing. However, in piezo-driven inkjet printheads, air entrapment can lead to malfunctioning of the jet formation. The piezoactuator is employed to actively monitor the channel acoustics and to identify distortions at an

  8. Determination of soil-entrapped methane

    Energy Technology Data Exchange (ETDEWEB)

    Alberto, M.C.R.; Neue, H.U.; Lantin, R.S.; Aduna, J.B. [Soil and Water Sciences Division, Manila (Philippines)

    1996-12-31

    A sampling method was developed and modified to sample soil from paddy fields for entrapped methane determination. A 25-cm long plexiglass tube (4.4-cm i.d.) fitted with gas bag was used to sample soil and entrapped gases to a depth of 15-cm. The sampling tube was shaken vigorously to release entrapped gases. Headspace gas in sampling tube and gas bag was analyzed for methane. The procedure was verified by doing field sampling weekly at an irrigated ricefield in the IRRI Research Farm on a Maahas clay soil. The modified sampling method gave higher methane concentration because it eliminated gas losses during sampling. The method gave 98% {+-} 5 recovery of soil-entrapped methane. Results of field sampling showed that the early growth stage of the rice plant, entrapped methane increased irrespective of treatment. This suggests that entrapped methane increased irrespective of treatment. This suggests that entrapped methane was primarily derived from fermentation of soil organic matter at the early growth stage. At the latter stage, the rice plant seems to be the major carbon source for methane production. 7 refs., 4 figs., 4 tabs.

  9. Fluxgate magnetorelaxometry for characterization of hydrogel polymerization kinetics and physical entrapment capacity.

    Science.gov (United States)

    Heim, E; Harling, S; Ludwig, F; Menzel, H; Schilling, M

    2008-05-21

    Hydrogels have the potential for providing drug delivery systems with long release rates. The polymerization kinetics and the physical entrapment capacity of photo-cross-linked hydroxyethyl methacrylate hydroxyethylstarch hydrogels are investigated with a non-destructive method. For this purpose, superparamagnetic nanoparticles as replacements for biomolecules are used as probes. By analyzing their magnetic relaxation behavior, the amounts of physically entrapped and mobile nanoparticles can be determined. The hydrogels were loaded with five different concentrations of nanoparticles. Different methods of analysis of the relaxation curves and the influence of the microviscosity are discussed. This investigation allows one to optimize the UV light irradiation time and to determine the amount of physically entrapped nanoparticles in the hydrogel network. It was found that the polymerization kinetics is faster for decreasing nanoparticle concentration but not all nanoparticles can be physically entrapped in the network.

  10. Fluxgate magnetorelaxometry for characterization of hydrogel polymerization kinetics and physical entrapment capacity

    Energy Technology Data Exchange (ETDEWEB)

    Heim, E; Ludwig, F; Schilling, M [Institut fuer Elektrische Messtechnik und Grundlagen der Elektrotechnik, TU Braunschweig, Hans-Sommer-Strasse 66, 38106 Braunschweig (Germany); Harling, S; Menzel, H [Institut fuer Technische Chemie, TU Braunschweig, Hans-Sommer-Strasse 10, 38106 Braunschweig (Germany)], E-mail: e.heim@tu-bs.de

    2008-05-21

    Hydrogels have the potential for providing drug delivery systems with long release rates. The polymerization kinetics and the physical entrapment capacity of photo-cross-linked hydroxyethyl methacrylate hydroxyethylstarch hydrogels are investigated with a non-destructive method. For this purpose, superparamagnetic nanoparticles as replacements for biomolecules are used as probes. By analyzing their magnetic relaxation behavior, the amounts of physically entrapped and mobile nanoparticles can be determined. The hydrogels were loaded with five different concentrations of nanoparticles. Different methods of analysis of the relaxation curves and the influence of the microviscosity are discussed. This investigation allows one to optimize the UV light irradiation time and to determine the amount of physically entrapped nanoparticles in the hydrogel network. It was found that the polymerization kinetics is faster for decreasing nanoparticle concentration but not all nanoparticles can be physically entrapped in the network.

  11. Fluxgate magnetorelaxometry for characterization of hydrogel polymerization kinetics and physical entrapment capacity

    International Nuclear Information System (INIS)

    Heim, E; Ludwig, F; Schilling, M; Harling, S; Menzel, H

    2008-01-01

    Hydrogels have the potential for providing drug delivery systems with long release rates. The polymerization kinetics and the physical entrapment capacity of photo-cross-linked hydroxyethyl methacrylate hydroxyethylstarch hydrogels are investigated with a non-destructive method. For this purpose, superparamagnetic nanoparticles as replacements for biomolecules are used as probes. By analyzing their magnetic relaxation behavior, the amounts of physically entrapped and mobile nanoparticles can be determined. The hydrogels were loaded with five different concentrations of nanoparticles. Different methods of analysis of the relaxation curves and the influence of the microviscosity are discussed. This investigation allows one to optimize the UV light irradiation time and to determine the amount of physically entrapped nanoparticles in the hydrogel network. It was found that the polymerization kinetics is faster for decreasing nanoparticle concentration but not all nanoparticles can be physically entrapped in the network

  12. Inhibitory effect of Lentinan entrapped in liposomes on hepatic metastasis in rats

    International Nuclear Information System (INIS)

    Yamashita, I.; Masuyama, K.; Yoshida, M.; Suzuki, Y.; Kasagi, T.; Tazawa, K.; Fujimaki, M.; Kawagoshi, T.; Maeda, M.; Honda, T.; Ochiai, H.

    1988-01-01

    Using the technique of Drug Delivery System, we experimentally attempted to examine whether the preventive i.v. administration of BRM entrapped in liposomes is useful or not for the cancer metastasis to the liver. As a BRM, we used Lentinan. The liposome used as a carrier in our study showed high stability both in vivo and in vitro with the mol ratio of phosphatidylcholine: cholesterol of 1. Also, high accumulation to reticuloendothelial system was evidenced. NK cell activity in the spleen and the liver on the day of the administration of AH60C hepatoma cells (2x10 6 cells) was higher by 1.3-2.3 times than those of the other groups. The survival ratio of tumor cells in the liver 8 h of tumor cells administration was significantly lower (P<0.01) than in the other groups. Rats with cancer metastasis to the liver on 30th day after the tumor cells administration were significantly decreased (P<0.01). These results suggested the usefulness of the i.v. administration of Lentinan entrapped in liposomes. (orig.)

  13. Synthetic nanoparticles of bovine serum albumin with entrapped salicylic acid

    Directory of Open Access Journals (Sweden)

    Bronze-Uhle ES

    2016-12-01

    Full Text Available ES Bronze-Uhle,1 BC Costa,1 VF Ximenes,2 PN Lisboa-Filho1 1Department of Physics, São Paulo State University (Unesp, School of Sciences, Bauru, São Paulo, Brazil; 2Department of Chemistry, São Paulo State University (Unesp, School of Sciences, Bauru, São Paulo, Brazil Abstract: Bovine serum albumin (BSA is highly water soluble and binds drugs or inorganic substances noncovalently for their effective delivery to various affected areas of the body. Due to the well-defined structure of the protein, containing charged amino acids, albumin nanoparticles (NPs may allow electrostatic adsorption of negatively or positively charged molecules, such that substantial amounts of drug can be incorporated within the particle, due to different albumin-binding sites. During the synthesis procedure, pH changes significantly. This variation modifies the net charge on the surface of the protein, varying the size and behavior of NPs as the drug delivery system. In this study, the synthesis of BSA NPs, by a desolvation process, was studied with salicylic acid (SA as the active agent. SA and salicylates are components of various plants and have been used for medication with anti-inflammatory, antibacterial, and antifungal properties. However, when administered orally to adults (usual dose provided by the manufacturer, there is 50% decomposition of salicylates. Thus, there has been a search for some time to develop new systems to improve the bioavailability of SA and salicylates in the human body. Taking this into account, during synthesis, the pH was varied (5.4, 7.4, and 9 to evaluate its influence on the size and release of SA of the formed NPs. The samples were analyzed using field-emission scanning electron microscopy, transmission electron microscopy, Fourier transform infrared, zeta potential, and dynamic light scattering. Through fluorescence, it was possible to analyze the release of SA in vitro in phosphate-buffered saline solution. The results of

  14. The synthesis and the electric-responsiveness of hydrogels entrapping natural polyelectrolyte

    International Nuclear Information System (INIS)

    Sutani, Kouichi; Kaetsu, Isao; Uchida, Kumao

    2001-01-01

    A mixture of vinyl monomer, a natural polyelectrolyte--hyaluronic acid--and crosslinker was polymerized and crosslinked to entrap the natural polymer into the synthetic gel. The controlled release of the model drug from the obtained gel was studied under the on-off switching of electric field. It was proved that electric-responsive drug releases were possible using hyaluronic acid entrapping gel and the electro-responsiveness was greatly affected by various factors such as degree of swelling, crosslinking density, kind and composition of vinyl monomer and crosslinkers

  15. The synthesis and the electric-responsiveness of hydrogels entrapping natural polyelectrolyte

    Science.gov (United States)

    Sutani, Kouichi; Kaetsu, Isao; Uchida, Kumao

    2001-04-01

    A mixture of vinyl monomer, a natural polyelectrolyte—hyaluronic acid—and crosslinker was polymerized and crosslinked to entrap the natural polymer into the synthetic gel. The controlled release of the model drug from the obtained gel was studied under the on-off switching of electric field. It was proved that electric-responsive drug releases were possible using hyaluronic acid entrapping gel and the electro-responsiveness was greatly affected by various factors such as degree of swelling, crosslinking density, kind and composition of vinyl monomer and crosslinkers.

  16. Subsartorial Entrapment of the Saphenous Nerve of a Competitive.

    Science.gov (United States)

    Dumitru, D; Windsor, R E

    1989-01-01

    In brief: A 40-year-old bodybuilder had a six- week history of progressively worsening pain of the medial part of her right knee that did not respond to rest and a nonsteroidal anti-inflammatory drug (NSAID). Somatosensory evoked potential readings suggested that both branches of the right saphenous nerve were entrapped. Management consisting of two intramuscular injections of bupivacaine, administrations of two different NSAIDs, and application of knee wraps around the subsartorial region resolved the patient's symptoms within five weeks. She then resumed an intensive lower-extremity exercise regimen without discomfort, in preparation for a bodybuilding competition.

  17. Drop impact splashing and air entrapment

    KAUST Repository

    Thoraval, Marie-Jean

    2013-03-01

    Drop impact is a canonical problem in fluid mechanics, with numerous applications in industrial as well as natural phenomena. The extremely simple initial configuration of the experiment can produce a very large variety of fast and complex dynamics. Scientific progress was made in parallel with major improvements in imaging and computational technologies. Most recently, high-speed imaging video cameras have opened the exploration of new phenomena occurring at the micro-second scale, and parallel computing allowed realistic direct numerical simulations of drop impacts. We combine these tools to bring a new understanding of two fundamental aspects of drop impacts: splashing and air entrapment. The early dynamics of a drop impacting on a liquid pool at high velocity produces an ejecta sheet, emerging horizontally in the neck between the drop and the pool. We show how the interaction of this thin liquid sheet with the air, the drop or the pool, can produce micro-droplets and bubble rings. Then we detail how the breakup of the air film stretched between the drop and the pool for lower impact velocities can produce a myriad of micro-bubbles.

  18. Diagnosis of Popliteal Venous Entrapment Syndrome by Magnetic Resonance Imaging Using Blood-Pool Contrast Agents

    International Nuclear Information System (INIS)

    Beitzke, Dietrich; Wolf, Florian; Juelg, Gregor; Lammer, Johannes; Loewe, Christian

    2011-01-01

    Popliteal vascular entrapment syndrome is caused by aberrations or hypertrophy of the gastrocnemius muscles, which compress the neurovascular structures of the popliteal fossa, leading to symptoms of vascular and degeneration as well as aneurysm formation. Imaging of popliteal vascular entrapment may be performed with ultrasound, magnetic resonance imaging (MRI), computed tomography angiography, and conventional angiography. The use of blood-pool contrast agents in MRI when popliteal vascular entrapment is suspected offers the possibility to perform vascular imaging with first-pass magnetic resonance angiographic, high-resolution, steady-state imaging and allows functional tests all within one examination with a single dose of contrast agent. We present imaging findings in a case of symptomatic popliteal vein entrapment diagnosed by the use of blood pool contrast-enhanced MRI.

  19. Bubble entrapment during sphere impact onto quiescent liquid surfaces

    KAUST Repository

    Marston, Jeremy

    2011-06-20

    We report observations of air bubble entrapment when a solid sphere impacts a quiescent liquid surface. Using high-speed imaging, we show that a small amount of air is entrapped at the bottom tip of the impacting sphere. This phenomenon is examined across a broad range of impact Reynolds numbers, 0.2 a Re = (DU0/Il) a 1.2\\' 105. Initially, a thin air pocket is formed due to the lubrication pressure in the air layer between the sphere and the liquid surface. As the liquid surface deforms, the liquid contacts the sphere at a finite radius, producing a thin sheet of air which usually contracts to a nearly hemispherical bubble at the bottom tip of the sphere depending on the impact parameters and liquid properties. When a bubble is formed, the final bubble size increases slightly with the sphere diameter, decreases with impact speed but appears independent of liquid viscosity. In contrast, for the largest viscosities tested herein, the entrapped air remains in the form of a sheet, which subsequently deforms upon close approach to the base of the tank. The initial contact diameter is found to conform to scalings based on the gas Reynolds number whilst the initial thickness of the air pocket or adimplea scales with a Stokes\\' number incorporating the influence of the air viscosity, sphere diameter and impact speed and liquid density. © 2011 Cambridge University Press.

  20. Quaternized triethanolamine-sebacoyl moieties in highly branched polymer architecture as a host for the entrapment of acid dyes in aqueous solutions

    Directory of Open Access Journals (Sweden)

    Meriem Bendjelloul

    2017-03-01

    Full Text Available This paper reports the synthesis of a hyperbranched polymer by a cost-effective one-step copolymerization of A3 and B2 monomers, namely, triethanolamine and sebacoyl chloride, respectively, followed by methylation of tertiary amine groups. The structure of the hyperbranched polymer QTEAS as an efficient material for the removal of acid dyes was demonstrated by Fourier transform infrared spectroscopy (FTIR, cross polarization magic angle spinning (CPMAS 13C NMR, thermogravimetric analysis (TGA, powder X-ray diffraction (DRX and scanning electron microscopy (SEM. The removal of indigo carmine (IC and Evans blue (EB was expected to be driven by the electrostatic attraction between positively charged quaternary ammonium groups within the hyperbranched polymer and the negatively charged dyes. The removal process was found to be closely connected to the total number of sulfonate groups on the surface of the dyes. Nonetheless, the ionic strength does not affect the dyes' removal efficiency by the hyperbranched polymer. The sorption capacities at saturation of the monolayer qmax were determined to be 213.22 mg g−1 and 214.13 mg g−1, for IC and EB, respectively, thus showing the greater affinity of QTEAS sorbent for both dyes. Despite its extended molecular structure, EB is removed with the same effectiveness as IC. Finally, the great efficiency of the highly branched polymer for dye removal from colored wastewater was clearly demonstrated.

  1. Anti-inflammatory activity of gel containing novel elastic niosomes entrapped with diclofenac diethylammonium.

    Science.gov (United States)

    Manosroi, A; Jantrawut, P; Manosroi, J

    2008-08-06

    The objective of this study was to develop a novel elastic bilayer vesicle entrapped with the non-steroidal anti-inflammatory drug (NSAID), diclofenac diethylammonium (DCFD) for topical use. Eighteen bilayer vesicular formulations composing of DPPC or Tween 61 or Span 60 mixed with cholesterol (at 1:1, 3:7 and 1:1 molar ratios, respectively) and ethanol at 0-25% (v/v), by chloroform film method with sonication were developed. The elastic Tween 61 niosomes which gave no sedimentation, no layer separation, unchanged particle sizes (about 200 nm) were selected to entrap DCFD. The entrapment efficiency of the drug in the conventional and elastic Tween 61 niosomes was 65 and 93%, respectively. At least 87% of DCFD determined by HPLC remained in elastic Tween 61 niosomes when kept at 4, 27 and 45 degrees C for 3 months. The deformability index values of the elastic niosomes were 13.76 and 3.44 times higher than the conventional niosomes entrapped and not entrapped with the drug, respectively, indicating the higher flexibility of the elastic vesicle especially, when entrapped with the drug. Transdermal absorption through excised rat skin was performed by vertical Franz diffusion cell at 32+/-2 degrees C for 6h. Gel containing elastic niosomes exhibited fluxes of DCFD in the stratum corneum (SC), deeper skin layer (viable epidermis and dermis, VED) and receiver chamber at 191.27+/-9.52, 16.97+/-2.77 and 3.76+/-0.54 microg/(cm2 h), whereas the commercial emulgel, containing an equivalent DCFD, gave 60.84+/-13.63, 7.33+/-1.70 and 0.14+/-0.01 microg/(cm2 h), respectively. The in vivo anti-inflammatory activity was evaluated by ethyl phenylpropiolate (EPP)-induced rat ear edema (n=3). DCFD entrapped in the developed elastic niosomes and incorporated in gel gave the same ear edema inhibition percentages of 23.81% at 30 min, but 2 and 9 times more inhibition percentages at 45 and 60 min than the commercial emulgel, respectively. This result has not only demonstrated the

  2. 6-mercaptopurine and daunorubicin double drug liposomes-preparation, drug-drug interaction and characterization.

    Science.gov (United States)

    Agrawal, Vineet; Paul, Manash K; Mukhopadhyay, Anup K

    2005-01-01

    This article addresses and investigates the dual incorporation of daunorubicin (DR) and 6-mercaptopurine (6-MP) in liposomes for better chemotherapy. These drugs are potential candidates for interaction due to the quinone (H acceptor) and hydroxyl (H donor) groups on DR and 6-MP, respectively. Interactions between the two drugs in solution were monitored by UV/Vis and fluorescence spectroscopy. Interaction between the two drugs inside the liposomes was evaluated by HPLC (for 6-MP) and by fluorescence spectroscopy (for daunorubicin) after phospholipase-mediated liposome lysis. Our results provide evidence for the lack of interaction between the two drugs in solution and in liposomes. The entrapment efficiencies of 6-MP in the neutral Phosphatidyl choline (PC):Cholesterol (Chol):: 2:1 and anionic PC:Chol:Cardiolipin (CL) :: 4:5:1 single and double drug liposomes were found to be 0.4% and 1.5% (on average), respectively. The entrapment efficiencies of DR in the neutral and anionic double drug liposomes were found to be 55% and 31%, respectively. The corresponding entrapment of daunorubicin in the single drug liposomes was found to be 62% on average. Our thin layer chromatography (TLC) and transmission electron microscopy (TEM) results suggest stability of lipid and liposomes, thus pointing plausible existence of double drug liposomes. Cytotoxicity experiments were performed by using both single drug and double drug liposomes. By comparing the results of phase contrast and fluorescence microscopy, it was observed that the double drug liposomes were internalized in the jurkat and Hut78 (highly resistant cell line) leukemia cells as viewed by the fluorescence of daunorubicin. The cytotoxicity was dose dependent and had shown a synergistic effect when double drug liposome was used.

  3. Anatomical study of middle cluneal nerve entrapment

    Directory of Open Access Journals (Sweden)

    Konno T

    2017-06-01

    Full Text Available Tomoyuki Konno,1 Yoichi Aota,2 Tomoyuki Saito,1 Ning Qu,3 Shogo Hayashi,3 Shinichi Kawata,3 Masahiro Itoh3 1Department of Orthopaedic Surgery, Yokohama City University, 2Department of Spine and Spinal Cord, Yokohama Brain and Spine Center, Yokohama City, 3Department of Anatomy, Tokyo Medical University, Tokyo, Japan Object: Entrapment of the middle cluneal nerve (MCN under the long posterior sacroiliac ligament (LPSL is a possible, and underdiagnosed, cause of low-back and/or leg symptoms. To date, detailed anatomical studies of MCN entrapment are few. The purpose of this study was to ascertain, using cadavers, the relationship between the MCN and LPSL and to investigate MCN entrapment. Methods: A total of 30 hemipelves from 20 cadaveric donors (15 female, 5 male designated for education or research, were studied by gross anatomical dissection. The age range of the donors at death was 71–101 years with a mean of 88 years. Branches of the MCN were identified under or over the gluteus maximus fascia caudal to the posterior superior iliac spine (PSIS and traced laterally as far as their finest ramification. Special attention was paid to the relationship between the MCN and LPSL. The distance from the branch of the MCN to the PSIS and to the midline and the diameter of the MCN were measured. Results: A total of 64 MCN branches were identified in the 30 hemipelves. Of 64 branches, 10 (16% penetrated the LPSL. The average cephalocaudal distance from the PSIS to where the MCN penetrated the LPSL was 28.5±11.2 mm (9.1–53.7 mm. The distance from the midline was 36.0±6.4 mm (23.5–45.2 mm. The diameter of the MCN branch traversing the LPSL averaged 1.6±0.5 mm (0.5–3.1 mm. Four of the 10 branches penetrating the LPSL had obvious constriction under the ligament. Conclusion: This is the first anatomical study illustrating MCN entrapment. It is likely that MCN entrapment is not a rare clinical entity. Keywords: middle cluneal nerve, sacroiliac joint

  4. Shopping cart injuries, entrapment, and childhood fatality.

    Science.gov (United States)

    Jensen, Lisbeth; Charlwood, Cheryl; Byard, Roger W

    2008-09-01

    Shopping carts may be associated with a variety of injuries, particularly in toddlers and young children. These usually relate to falls from carts or to tip-overs. Injuries that are sustained include hematomas/contusions, abrasions, lacerations, fractures, and fingertip amputations. Fatal episodes are uncommon and are usually due to blunt craniocerebral trauma from falls. A case involving a 19-month-old girl is reported who became entrapped when she inserted her head through the side frame of a cart that had been removed from a supermarket and left at her home address. Death was caused by neck compression. Although rare, the potential for lethal entrapment during unsupervised play means that the presence of stray shopping carts at private residences and in public places, including playgrounds and parks, is of concern. Strategies, such as coin deposits, should be encouraged to assist in the return of such carts to supermarkets.

  5. Suprascapular nerve entrapment in newsreel cameramen.

    Science.gov (United States)

    Karataş, Gülçin Kaymak; Göğüş, Feride

    2003-03-01

    To determine presence of suprascapular nerve entrapment in a group of newsreel cameramen. Thirty-six men working as newsreel cameramen participated in the study. In addition to musculoskeletal and neurologic examinations, bilateral suprascapular nerve conduction studies and needle electromyography were performed. A group of 19 healthy, male volunteers were included in the study as normal controls for suprascapular nerve conduction studies. In newsreel cameramen, mean suprascapular nerve latency was 3.20 +/- 0.56 msec and 2.84 +/- 0.36 msec for right and left shoulders, respectively (P = 0.001). The mean latency difference between right and left suprascapular nerves was -0.05 +/- 0.19 msec in the control group and 0.36 +/- 0.58 msec in the cameramen group (P mobile camera on the shoulder might cause suprascapular nerve entrapment in newsreel cameramen. This could be considered an occupational disorder of the suprascapular nerve, like meat-packer's neuropathy.

  6. Perceived neighborhood illicit drug selling, peer illicit drug disapproval and illicit drug use among U.S. high school seniors

    Science.gov (United States)

    2014-01-01

    Background This study examined associations between perceived neighborhood illicit drug selling, peer illicit drug disapproval and illicit drug use among a large nationally representative sample of U.S. high school seniors. Methods Data come from Monitoring the Future (2007–2011), an annual cross-sectional survey of U.S. high school seniors. Students reported neighborhood illicit drug selling, friend drug disapproval towards marijuana and cocaine use, and past 12-month and past 30-day illicit drug use (N = 10,050). Multinomial logistic regression models were fit to explain use of 1) just marijuana, 2) one illicit drug other than marijuana, and 3) more than one illicit drug other than marijuana, compared to “no use”. Results Report of neighborhood illicit drug selling was associated with lower friend disapproval of marijuana and cocaine; e.g., those who reported seeing neighborhood sales “almost every day” were less likely to report their friends strongly disapproved of marijuana (adjusted odds ratio [AOR] = 0.38, 95% CI: 0.29, 0.49) compared to those who reported never seeing neighborhood drug selling and reported no disapproval. Perception of neighborhood illicit drug selling was also associated with past-year drug use and past-month drug use; e.g., those who reported seeing neighborhood sales “almost every day” were more likely to report 30-day use of more than one illicit drug (AOR = 11.11, 95% CI: 7.47, 16.52) compared to those who reported never seeing neighborhood drug selling and reported no 30-day use of illicit drugs. Conclusions Perceived neighborhood drug selling was associated with lower peer disapproval and more illicit drug use among a population-based nationally representative sample of U.S. high school seniors. Policy interventions to reduce “open” (visible) neighborhood drug selling (e.g., problem-oriented policing and modifications to the physical environment such as installing and monitoring surveillance cameras) may

  7. Imaging appearance of entrapped periosteum within a distal femoral Salter-Harris II fracture

    International Nuclear Information System (INIS)

    Chen, Johnathan; Abel, Mark F.; Fox, Michael G.

    2015-01-01

    Salter Harris II fractures of the distal femur are associated with a high incidence of complications, especially premature physeal closure. Many risk factors for this high rate of premature physeal closure have been proposed. More recently, entrapment of periosteum within the physis has been suggested as an additional predisposing factor for premature physeal closure. The radiographic diagnosis of entrapped soft tissues, including periosteum, can be suggested in the setting of a Salter-Harris II fracture when the fracture does not reduce and physeal widening >3 mm remains. We report a patient who sustained a distal femoral Salter-Harris II fracture following a valgus injury. The patient had persistent distal medial physeal widening >5 mm following attempted reduction. A subsequent MRI revealed a torn periosteum entrapped within the distal femoral physis. Following removal of the periosteum, the patient developed a leg length discrepancy which required physiodesis of the contralateral distal femur. We present this case to raise awareness of the importance of having a high index of suspicion of periosteal entrapment in the setting of Salter-Harris II fractures since most consider entrapped periosteum an indication for surgery. (orig.)

  8. Chronic Localized Back Pain Due to Posterior Cutaneous Nerve Entrapment Syndrome (POCNES): A New Diagnosis.

    Science.gov (United States)

    Boelens, Oliver B; Maatman, Robert C; Scheltinga, Marc R; van Laarhoven, Kees; Roumen, Rudi M

    2017-03-01

    Most patients with chronic back pain suffer from degenerative thoracolumbovertebral disease. However, the following case illustrates that a localized peripheral nerve entrapment must be considered in the differential diagnosis of chronic back pain. We report the case of a 26-year-old woman with continuous excruciating pain in the lower back area. Previous treatment for nephroptosis was to no avail. On physical examination the pain was present in a 2 x 2 cm area overlying the twelfth rib some 4 cm lateral to the spinal process. Somatosensory testing using swab and alcohol gauze demonstrated the presence of skin hypo- and dysesthesia over the painful area. Local pressure on this painful spot elicited an extreme pain response that did not irradiate towards the periphery. These findings were highly suggestive of a posterior version of the anterior cutaneous nerve entrapment syndrome (ACNES), a condition leading to a severe localized neuropathic pain in anterior portions of the abdominal wall. She demonstrated a beneficial albeit temporary response after lidocaine infiltration as dictated by an established diagnostic and treatment protocol for ACNES. She subsequently underwent a local neurectomy of the involved superficial branch of the intercostal nerve. This limited operation had a favorable outcome resulting in a pain-free return to normal activities up to this very day (follow-up of 24 months).We propose to name this novel syndrome "posterior cutaneous nerve entrapment syndrome" (POCNES). Each patient with chronic localized back pain should undergo simple somatosensory testing to detect the presence of overlying skin hypo- and dysesthesia possibly reflecting an entrapped posterior cutaneous nerve.Key words: Chronic pain, back pain, posterior cutaneous nerve entrapment, peripheral nerve entrapment, surgical treatment for pain, anterior cutaneous nerve entrapment.

  9. [Targeting high-risk drugs to optimize clinical pharmacists' intervention].

    Science.gov (United States)

    Mouterde, Anne-Laure; Bourdelin, Magali; Maison, Ophélie; Coursier, Sandra; Bontemps, Hervé

    2016-12-01

    By the Order of 6 April 2011, the pharmacist must validate all the prescriptions containing "high-risk drugs" or those of "patients at risk". To optimize this clinical pharmacy activity, we identified high-risk drugs. A list of high-risk drugs has been established using literature, pharmacists' interventions (PI) performed in our hospital and a survey sent to hospital pharmacists. In a prospective study (analysis of 100 prescriptions for each high-risk drug selected), we have identified the most relevant to target. We obtained a statistically significant PI rate (P<0.05) for digoxin, oral anticoagulants direct, oral methotrexate and colchicine. This method of targeted pharmaceutical validation based on high-risk drugs is relevant to detect patients with high risk of medicine-related illness. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  10. Ulnar nerve entrapment in a French horn player.

    Science.gov (United States)

    Hoppmann, R A

    1997-10-01

    Nerve entrapment syndromes are frequent among musicians. Because of the demands on the musculoskeletal system and the great agility needed to per-form, musicians often present with vague complaints early in the course of entrapment, which makes the diagnosis a challenge for the clinician. Presented here is such a case of ulnar nerve entrapment at the left elbow of a French horn player. This case points out some of the difficulties in establishing a diagnosis of nerve entrapment in musicians. It also supports the theory that prolonged elbow flexion and repetitive finger movement contribute to the development of ulnar entrapment at the elbow. Although surgery is not required for most of the musculoskeletal problems of musicians, release of an entrapped nerve refractory to conservative therapy may be career-saving for the musician.

  11. Flexible, cathodoluminescent and free standing mesoporous silica films with entrapped quasi-2D perovskites

    Science.gov (United States)

    Vassilakopoulou, Anastasia; Papadatos, Dionysios; Koutselas, Ioannis

    2017-04-01

    The effective entrapment of hybrid organic-inorganic semiconductors (HOIS) into mesoporous polymer-silica hybrid matrices, formed as free standing flexible films, is presented for the first time. A blend of quasi-2D HOIS, simply synthesized by mixing two-dimensional (2D) and three dimensional (3D) HOIS, exhibiting strong photoluminescence, is embedded into porous silica matrices during the sol-gel synthesis, using tetraethylorthosilicate as precursor and Pluronic F-127 triblock copolymer as structure directing agent, under acidic conditions. The final nanostructure hybrid forms flexible, free standing films, presenting high cathodoluminescence and long stable excitonic luminescence, indicating the protective character of the hybrid matrix towards the entrapped perovskite. A significant result is that the photoluminescence of the entrapped HOIS is not affected even after films' prolonged exposure to water.

  12. Mass entrapment and lysis of Mesodinium rubrum cells in mucus threads observed in cultures with Dinophysis

    DEFF Research Database (Denmark)

    Ojamäe, Karin; Hansen, Per Juel; Lips, Inga

    2016-01-01

    The entrapment and death of the ciliate Mesodinium rubrum in the mucus threads in cultures with Dinophysis is described and quantified. Feeding experiments with different concentrations and predator–prey ratios of Dinophysis acuta, Dinophysis acuminata and M. rubrum to study the motility loss...... and aggregate formation of the ciliates and the feeding behaviour of Dinophysis were carried out. In cultures of either Dinophysis species, the ciliates became entrapped in the mucus, which led to the formation of immobile aggregates of M. rubrum and subsequent cell lysis. The proportion of entrapped ciliates...... was influenced by the concentration of Dinophysis and the ratio of predator and prey in the cultures. At high cell concentrations of prey (136 cells mL−1) and predator (100 cells mL−1), a maximum of 17% of M. rubrum cells became immobile and went through cell lysis. Ciliates were observed trapped in the mucus...

  13. Patents Associated with High-Cost Drugs in Australia

    OpenAIRE

    Christie, Andrew F.; Dent, Chris; McIntyre, Peter; Wilson, Lachlan; Studdert, David M.

    2013-01-01

    Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by "evergreening" blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent...

  14. High-Throughput Cytochrome P450 Cocktail Inhibition Assay for Assessing Drug-Drug and Drug-Botanical Interactions.

    Science.gov (United States)

    Li, Guannan; Huang, Ke; Nikolic, Dejan; van Breemen, Richard B

    2015-11-01

    Detection of drug-drug interactions is essential during the early stages of drug discovery and development, and the understanding of drug-botanical interactions is important for the safe use of botanical dietary supplements. Among the different forms of drug interactions that are known, inhibition of cytochrome P450 (P450) enzymes is the most common cause of drug-drug or drug-botanical interactions. Therefore, a rapid and comprehensive mass spectrometry-based in vitro high-throughput P450 cocktail inhibition assay was developed that uses 10 substrates simultaneously against nine CYP isoforms. Including probe substrates for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and two probes targeting different binding sites of CYP3A4/5, this cocktail simultaneously assesses at least as many P450 enzymes as previous assays while remaining among the fastest due to short incubation times and rapid analysis using ultrahigh pressure liquid chromatography-tandem mass spectrometry. The method was validated using known inhibitors of each P450 enzyme and then shown to be useful not only for single-compound testing but also for the evaluation of potential drug-botanical interactions using the botanical dietary supplement licorice (Glycyrrhiza glabra) as an example. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  15. Development of liposomes entrapped in alginate beads for the treatment of colorectal cancer.

    Science.gov (United States)

    Bansal, Divya; Gulbake, Arvind; Tiwari, Jyoti; Jain, Sanjay K

    2016-01-01

    Folic Acid conjugated liposomes encapsulating Oxaliplatin (L-OHP) were entrapped in alginate beads and further coated with Eudragit-S-100 for effective delivery to colon tumors. Liposomes were prepared by cast film method and folic acid was coupled on the surface of liposomes. They were further entrapped in alginate beads which were Eudragit coated for degradation in the colonic region. The prepared beads were characterized for shape and surface morphology, percentage entrapment efficiency and drug release studies. The in vitro drug release was investigated using a USP dissolution paddle type apparatus in different simulated gastrointestinal fluids. In vivo studies of the beads containing free drug, folic acid coupled and uncoupled liposomes bearing L-OHP was administered orally at the dose of 10mg L-OHP/kg body weight to tumor bearing NUDE/SCID mice. γ-Scintigraphic study showed that Eudragit coated alginate beads entered into the colon of Balb/c mice between 4.20 and 4.50h after oral administration. In vivo data showed that folic acid coupled liposomes entrapped in alginate beads delivered 2.82 ± 0.58 and 21.52 ± 2.76 μg L-OHP/g tissues in the colon and tumor after 12h, reflecting its targeting potential to colon and tumor. The results clearly demonstrate that Eudragit coated calcium alginate beads bearing folic acid coupled liposome can be used as a prospective carrier for drug delivery to colon specific tumor. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Ultra high performance liquid chromatography of seized drugs

    NARCIS (Netherlands)

    Lurie, I.S.

    2010-01-01

    The primary goal of this thesis is to investigate the use of ultra high performance liquid chromatography (UHPLC) for the analysis of seized drugs. This goal was largely achieved and significant progress was made in achieving improved separation and detection of drugs of forensic interest.

  17. Patents associated with high-cost drugs in Australia.

    Directory of Open Access Journals (Sweden)

    Andrew F Christie

    Full Text Available Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by "evergreening" blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug's originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators.

  18. Patents associated with high-cost drugs in Australia.

    Science.gov (United States)

    Christie, Andrew F; Dent, Chris; McIntyre, Peter; Wilson, Lachlan; Studdert, David M

    2013-01-01

    Australia, like most countries, faces high and rapidly-rising drug costs. There are longstanding concerns about pharmaceutical companies inappropriately extending their monopoly position by "evergreening" blockbuster drugs, through misuse of the patent system. There is, however, very little empirical information about this behaviour. We fill the gap by analysing all of the patents associated with 15 of the costliest drugs in Australia over the last 20 years. Specifically, we search the patent register to identify all the granted patents that cover the active pharmaceutical ingredient of the high-cost drugs. Then, we classify the patents by type, and identify their owners. We find a mean of 49 patents associated with each drug. Three-quarters of these patents are owned by companies other than the drug's originator. Surprisingly, the majority of all patents are owned by companies that do not have a record of developing top-selling drugs. Our findings show that a multitude of players seek monopoly control over innovations to blockbuster drugs. Consequently, attempts to control drug costs by mitigating misuse of the patent system are likely to miss the mark if they focus only on the patenting activities of originators.

  19. 6-mercaptopurine (6-MP) entrapped stealth liposomes for improvement of leukemic treatment without hepatotoxicity and nephrotoxicity.

    Science.gov (United States)

    Umrethia, Manish; Ghosh, Pradip Kumar; Majithya, Rita; Murthy, R S R

    2007-03-01

    6-mercaptopurine (6-MP) is a purine analogue used in childhood leukemia. Because of the oral bioavailability of 6-MP is low and highly variable, the aim of this study was to develop a new parenteral formulation that can prolong the biological half-life of the drug, improve its therapeutic efficacy, and its associated reduce side effects. Conventional and stealth 6-MP liposomes were prepared by a thin film hydration technique followed by a high-pressure homogenization process and characterized for percent entrapment efficiency (%EE), particle size, and stability in human plasma. Pharmacokinetic, tissue distribution, and biochemical analysis were performed after intravenous (IV) administration of all formulations of 6-MP on rats. The conventional liposomes were found less stable than stealth liposomes in human plasma at 37 degrees C. Stealth liposomes exhibited high peak plasma concentration (C(max)), and long circulating capacity in blood and biological half-life. The uptake of stealth liposomes by the liver and spleen and accumulation in the kidney were significantly less than that of conventional liposomes and the free drug. Serum urea, creatinine, GOT (Glutamic Oxaloacetic Transaminase), and GPT (Glutamic Pyruvic Transaminase) increased significantly in rats given an IV injection of conventional liposomes and the free drug, but not in those administered with the same dose of stealth liposomes. Stealth liposomes may help to increase therapeutic efficacy of 6-MP and to reduce total amount of dose as well as frequency of the dose. It also may reduce the possibility of the risk of toxicity to the liver and kidney generally associated with free 6-MP.

  20. Liposome Entrapment of Bacteriophages Improves Wound Healing in a Diabetic Mouse MRSA Infection

    Directory of Open Access Journals (Sweden)

    Sanjay Chhibber

    2018-03-01

    Full Text Available Diabetic populations are more prone to developing wound infections which results in poor and delayed wound healing. Infection with drug resistant organisms further worsen the situation, driving searches for alternative treatment approaches such as phage therapy. Major drawback of phage therapy, however, is low phage persistence in situ, suggesting further refinement of the approach. In the present work we address this issue by employing liposomes as delivery vehicles. A liposome entrapped phage cocktail was evaluated for its ability to resolve a Staphylococcus aureus-induced diabetic excission wound infection. Two characterized S. aureus specific lytic phages, MR-5 and MR-10 alone, in combination (cocktail, or entrapped in liposomes (versus as free phages were assesed for their therapeutic efficacy in resolving diabetic wound infection. Mice treated with free phage cocktail showed significant reduction in wound bioburden, greater wound contraction and faster tissue healing than with free monophage therapy. However, to further enhance the availability of viable phages the encapsulation of phage cocktail in the liposomes was done. Results of in vitro stability studies and in vivo phage titer determination, suggests that liposomal entrapment of phage cocktail can lead to better phage persistence at the wound site. A 2 log increase in phage titre, however, was observed at the wound site with liposome entrapped as compared to the free phage cocktail, and this was associaed with increased rates of infection resolution and wound healing. Entrapment of phage cocktails within liposomes thus could represent an attractive approach for treatment of bacterial infections, not responding to antibiotis as increased phage persistence in vitro and in vivo at the wound site was observed.

  1. Improved drug loading and antibacterial activity of minocycline-loaded PLGA nanoparticles prepared by solid/oil/water ion pairing method

    Science.gov (United States)

    Kashi, Tahereh Sadat Jafarzadeh; Eskandarion, Solmaz; Esfandyari-Manesh, Mehdi; Marashi, Seyyed Mahmoud Amin; Samadi, Nasrin; Fatemi, Seyyed Mostafa; Atyabi, Fatemeh; Eshraghi, Saeed; Dinarvand, Rassoul

    2012-01-01

    Background Low drug entrapment efficiency of hydrophilic drugs into poly(lactic-co-glycolic acid) (PLGA) nanoparticles is a major drawback. The objective of this work was to investigate different methods of producing PLGA nanoparticles containing minocycline, a drug suitable for periodontal infections. Methods Different methods, such as single and double solvent evaporation emulsion, ion pairing, and nanoprecipitation were used to prepare both PLGA and PEGylated PLGA nanoparticles. The resulting nanoparticles were analyzed for their morphology, particle size and size distribution, drug loading and entrapment efficiency, thermal properties, and antibacterial activity. Results The nanoparticles prepared in this study were spherical, with an average particle size of 85–424 nm. The entrapment efficiency of the nanoparticles prepared using different methods was as follows: solid/oil/water ion pairing (29.9%) > oil/oil (5.5%) > water/oil/water (4.7%) > modified oil/water (4.1%) > nano precipitation (0.8%). Addition of dextran sulfate as an ion pairing agent, acting as an ionic spacer between PEGylated PLGA and minocycline, decreased the water solubility of minocycline, hence increasing the drug entrapment efficiency. Entrapment efficiency was also increased when low molecular weight PLGA and high molecular weight dextran sulfate was used. Drug release studies performed in phosphate buffer at pH 7.4 indicated slow release of minocycline from 3 days to several weeks. On antibacterial analysis, the minimum inhibitory concentration and minimum bactericidal concentration of nanoparticles was at least two times lower than that of the free drug. Conclusion Novel minocycline-PEGylated PLGA nanoparticles prepared by the ion pairing method had the best drug loading and entrapment efficiency compared with other prepared nanoparticles. They also showed higher in vitro antibacterial activity than the free drug. PMID:22275837

  2. A high content screening assay to predict human drug-induced liver injury during drug discovery.

    Science.gov (United States)

    Persson, Mikael; Løye, Anni F; Mow, Tomas; Hornberg, Jorrit J

    2013-01-01

    Adverse drug reactions are a major cause for failures of drug development programs, drug withdrawals and use restrictions. Early hazard identification and diligent risk avoidance strategies are therefore essential. For drug-induced liver injury (DILI), this is difficult using conventional safety testing. To reduce the risk for DILI, drug candidates with a high risk need to be identified and deselected. And, to produce drug candidates without that risk associated, risk factors need to be assessed early during drug discovery, such that lead series can be optimized on safety parameters. This requires methods that allow for medium-to-high throughput compound profiling and that generate quantitative results suitable to establish structure-activity-relationships during lead optimization programs. We present the validation of such a method, a novel high content screening assay based on six parameters (nuclei counts, nuclear area, plasma membrane integrity, lysosomal activity, mitochondrial membrane potential (MMP), and mitochondrial area) using ~100 drugs of which the clinical hepatotoxicity profile is known. We find that a 100-fold TI between the lowest toxic concentration and the therapeutic Cmax is optimal to classify compounds as hepatotoxic or non-hepatotoxic, based on the individual parameters. Most parameters have ~50% sensitivity and ~90% specificity. Drugs hitting ≥2 parameters at a concentration below 100-fold their Cmax are typically hepatotoxic, whereas non-hepatotoxic drugs typically hit based on nuclei count, MMP and human Cmax, we identified an area without a single false positive, while maintaining 45% sensitivity. Hierarchical clustering using the multi-parametric dataset roughly separates toxic from non-toxic compounds. We employ the assay in discovery projects to prioritize novel compound series during hit-to-lead, to steer away from a DILI risk during lead optimization, for risk assessment towards candidate selection and to provide guidance of safe

  3. A new diagnostic approach to popliteal artery entrapment syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Williams, Charles; Kennedy, Dominic; Bastian-Jordan, Matthew; Hislop, Matthew; Cramp, Brendan; Dhupelia, Sanjay [Queensland X-Ray, Sunnybank, Queensland, 4109 (Australia)

    2015-09-15

    A new method of diagnosing and defining functional popliteal artery entrapment syndrome is described. By combining ultrasonography and magnetic resonance imaging techniques with dynamic plantarflexion of the ankle against resistance, functional entrapment can be demonstrated and the location of the arterial occlusion identified. This combination of imaging modalities will also define muscular anatomy for guiding intervention such as surgery or Botox injection.

  4. A new diagnostic approach to popliteal artery entrapment syndrome

    International Nuclear Information System (INIS)

    Williams, Charles; Kennedy, Dominic; Bastian-Jordan, Matthew; Hislop, Matthew; Cramp, Brendan; Dhupelia, Sanjay

    2015-01-01

    A new method of diagnosing and defining functional popliteal artery entrapment syndrome is described. By combining ultrasonography and magnetic resonance imaging techniques with dynamic plantarflexion of the ankle against resistance, functional entrapment can be demonstrated and the location of the arterial occlusion identified. This combination of imaging modalities will also define muscular anatomy for guiding intervention such as surgery or Botox injection

  5. High throughput electrophysiology: new perspectives for ion channel drug discovery

    DEFF Research Database (Denmark)

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter

    2003-01-01

    . A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct....... The introduction of new powerful HTS electrophysiological techniques is predicted to cause a revolution in ion channel drug discovery....

  6. High-risk sexual behavior among drug-using men.

    Science.gov (United States)

    Seidman, S N; Sterk-Elifson, C; Aral, S O

    1994-01-01

    Drug-using men are at high risk for acquisition and transmission of STD, presumably due to the risky behaviors practiced in environments of drug use. To study behaviors associated with STD transmission among drug-using men. Drug outreach workers distributed vouchers to self-identified drug-using men in urban Atlanta. Vouchers could be redeemed for cash at a storefront clinic where subjects provided urine for a urethritis screening test (leukocyte esterase test) and a drug screen, and were interviewed. Of 382 voucher recipients, 252 (66%) came to the clinic. Subjects were predominantly black (92%), homeless (70%), and aged 20 to 40 (88%). All used illicit drugs; none were currently receiving drug abuse treatment. Urine drug screen confirmed recent cocaine use in 63%, and recent opiate use in 4%. Three-fourths reported a history of STD, mostly gonorrhea. In the preceding 3 months, 14% had not had sex, 80% had sex exclusively with women, 4% had sex with both men and women, and 2% had sex exclusively with men. Of the heterosexually active men, 29% had 5 or more recent partners. Compared to other heterosexually active men, these men were more likely to always use alcohol or crack before having sex (prevalence ratio [PR] = 2.0, 95% CI = 1.3-2.5) and to drink alcohol every day (PR = 2.0, 95% CI = 1.2-3.3). Daily crack use was associated with choosing partners at elevated STD risk; daily alcohol use with having more partners. Positive drug screen for cocaine was associated with self-reported crack use. Urethritis, detected in 16%, was not correlated with behavior. A substantial number of drug-using men practice high-risk sexual behavior and should be targeted for intervention. Monetary and other incentives should be considered for recruitment. Further study is needed to clarify the relationship between sexual behavior, cocaine use, and STD.

  7. Cochlear vertebral entrapment syndrome: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Liu Chinghsiung; Lin Shinnkuang E-mail: sk1943@adm.cgmh.org.tw; Chang Yeujhy

    2001-11-01

    The authors describe a patient with isolated involvement of vestibulocochlear nerve by a huge vascular loop from vertebral dolichoectasia. No other neurological deficit was found except for unilateral hearing loss. Abnormal brainstem auditory evoked potential study indicated a retrocochlear lesion. The brain computed tomography (CT) and magnetic resonance imaging (MRI) studies demonstrated an abnormally enhanced vascular lesion impinged on the left porus acusticus with a displacement of the brainstem to the right. There was no infarction in the brainstem. A cerebral angiography demonstrated a megadolichoectatic horizontal loop at the intracranial portion of the left vertebral artery. There was no thrombus or atherosclerosis in the vertebrobasilar system. A mechanical compression by a vascular loop is the only possible pathogenesis for hearing loss. The authors diagnose this condition as cochlear vertebral entrapment syndrome.

  8. Albumin–Polymer–Drug Conjugates: Long Circulating, High Payload Drug Delivery Vehicles

    DEFF Research Database (Denmark)

    Smith, Anton Allen Abbotsford; Zuwala, Kaja; Pilgram, Oliver

    2016-01-01

    Albumin is an exquisite tool of nature used in biomedicine to achieve long blood residence time for drugs, but the payload it can carry is typically limited to one molecule per protein. In contrast, synthetic macromolecular prodrugs contain multiple copies of drugs per polymer chain but offer only...... a marginal increase in the circulation lifetime of the drugs. We combine the benefits of the two platforms and at the same time overcome their respective limitations. Specifically, we develop the synthesis of albumin–polymer–drug conjugates to obtain long circulating, high payload drug delivery vehicles....... In vivo data validate that albumin endows the conjugate with a blood residence time similar to that of the protein and well exceeding that of the polymer. Therapeutic activity of the conjugates is validated using prodrugs of panobinostat, an HIV latency reversal agent, in which case the conjugates matched...

  9. Amperometric biosensor for hydrogen peroxide based on hemoglobin entrapped in titania sol-gel film

    International Nuclear Information System (INIS)

    Yu Jiuhong; Ju Huangxian

    2003-01-01

    Hemoglobin (Hb) was entrapped in a titania sol-gel matrix and used as a mimetic peroxidase to construct a novel amperometric biosensor for hydrogen peroxide. The Hb entrapped titania sol-gel film was obtained with a vapor deposition method, which simplified the traditional sol-gel process for protein immobilization. The morphologies of both titania sol-gel and the Hb films were characterized using scanning electron microscopy (SEM) and proved to be chemically clean, porous, homogeneous. This matrix provided a biocompatible microenvironment for retaining the native structure and activity of the entrapped Hb and a very low mass transport barrier to the substrates. H 2 O 2 could be reduced by the catalysis of the entrapped hemoglobin at -300 mV without any mediator. The reagentless H 2 O 2 sensor exhibited a fast response (less than 5 s) and sensitivity as high as 1.29 mA mM -1 cm -2 . The linear range for H 2 O 2 determination was from 5.0x10 -7 to 5.4x10 -5 M with a detection limit of 1.2x10 -7 M. The apparent Michaelis-Menten constant of the encapsulated hemoglobin was calculated to be 0.18±0.02 mM. The stability of the biosensor was also evaluated

  10. Drug response prediction in high-risk multiple myeloma

    DEFF Research Database (Denmark)

    Vangsted, A J; Helm-Petersen, S; Cowland, J B

    2018-01-01

    from high-risk patients by GEP70 at diagnosis from Total Therapy 2 and 3A to predict the response by the DRP score of drugs used in the treatment of myeloma patients. The DRP score stratified patients further. High-risk myeloma with a predicted sensitivity to melphalan by the DRP score had a prolonged...

  11. Medial and Lateral Plantar Nerve Entrapment

    Science.gov (United States)

    ... Generic and Brand Natural Products, Search Drug Interactions Pill Identifier Commonly searched drugs Aspirin Metformin Warfarin Tramadol Lactulose Ranitidine News & Commentary Recent News Strict Gun Laws Spare Young Lives: Study 'Smart Dresser' Might Help Alzheimer's Patients Clothe Themselves AHA: ...

  12. A high-density lipoprotein-mediated drug delivery system.

    Science.gov (United States)

    Mo, Zhong-Cheng; Ren, Kun; Liu, Xing; Tang, Zhen-Li; Yi, Guang-Hui

    2016-11-15

    High-density lipoprotein (HDL) is a comparatively dense and small lipoprotein that can carry lipids as a multifunctional aggregate in plasma. Several studies have shown that increasing the levels or improving the functionality of HDL is a promising target for treating a wide variety of diseases. Among lipoproteins, HDL particles possess unique physicochemical properties, including naturally synthesized physiological components, amphipathic apolipoproteins, lipid-loading and hydrophobic agent-incorporating characteristics, specific protein-protein interactions, heterogeneity, nanoparticles, and smaller size. Recently, the feasibility and superiority of using HDL particles as drug delivery vehicles have been of great interest. In this review, we summarize the structure, constituents, biogenesis, remodeling, and reconstitution of HDL drug delivery systems, focusing on their delivery capability, characteristics, applications, manufacturing, and drug-loading and drug-targeting characteristics. Finally, the future prospects are presented regarding the clinical application and challenges of using HDL as a pharmacodelivery carrier. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Renal artery entrapment by the diaphragmatic crus

    International Nuclear Information System (INIS)

    Thony, F.; Baguet, J.-P.; Rodiere, M.; Sessa, C.; Janbon, B; Ferretti, G.

    2005-01-01

    The aim of this study is to describe renal artery entrapment (RAE) by the diaphragmatic crus and to elucidate the diagnostic and therapeutic approach to this entity. From 1995 to 2002, 15 patients (mean age 65) were found to have a RAE. They were investigated by CT scan (n=14) and/or MRA (n=2) for hypertension (n=7), chronic renal insufficiency (n=4) or aneurysms (n=4). The right (n=11) or the left (n=4) renal artery (RA) was involved. The compression was ostial (n=8) or truncal (n=7), and was ≥50% in eight cases. The course of the RA along the aorta on angiographic views (n=8) or a concentric ostial stenosis in a patient free of atheromatous lesions (n=7) were two findings suggestive of an RAE. Seven RAEs were indicated for treatment but only three were treated, by mean of stenting. Among the latter, two stents were patent at 6-month follow-up and one evolved to restenosis because of a stent fracture. RAEs may be suspected on angiographic views and proved by cross-sectional imaging because of specific imaging features. It is of importance to detect this etiology of RA stenosis because angioplasty with stenting is probably not always advisable. (orig.)

  14. Characterization of ancient Indian iron and entrapped slag ...

    Indian Academy of Sciences (India)

    year old Indian iron using microprobe techniques (EDS, XRD and PIXE). Several different local locations in the iron matrix and in the entrapped slag inclusions were analyzed. The P content of the metallic iron matrix was very heterogeneous.

  15. Polylactic acid nano- and microchamber arrays for encapsulation of small hydrophilic molecules featuring drug release via high intensity focused ultrasound.

    Science.gov (United States)

    Gai, Meiyu; Frueh, Johannes; Tao, Tianyi; Petrov, Arseniy V; Petrov, Vladimir V; Shesterikov, Evgeniy V; Tverdokhlebov, Sergei I; Sukhorukov, Gleb B

    2017-06-01

    Long term encapsulation combined with spatiotemporal release for a precisely defined quantity of small hydrophilic molecules on demand remains a challenge in various fields ranging from medical drug delivery, controlled release of catalysts to industrial anti-corrosion systems. Free-standing individually sealed polylactic acid (PLA) nano- and microchamber arrays were produced by one-step dip-coating a PDMS stamp into PLA solution for 5 s followed by drying under ambient conditions. The wall thickness of these hydrophobic nano-microchambers is tunable from 150 nm to 7 μm by varying the PLA solution concentration. Furthermore, small hydrophilic molecules were successfully in situ precipitated within individual microchambers in the course of solvent evaporation after sonicating the PLA@PDMS stamp to remove air-bubbles and to load the active substance containing solvent. The cargo capacity of single chambers was determined to be in the range of several picograms, while it amounts to several micrograms per cm 2 . Two different methods for sealing chambers were compared: microcontact printing versus dip-coating whereby microcontact printing onto a flat PLA sheet allows for entrapment of micro-air-bubbles enabling microchambers with both ultrasound responsiveness and reduced permeability. Cargo release triggered by external high intensity focused ultrasound (HIFU) stimuli is demonstrated by experiment and compared with numerical simulations.

  16. High throughput electrophysiology: new perspectives for ion channel drug discovery

    DEFF Research Database (Denmark)

    Willumsen, Niels J; Bech, Morten; Olesen, Søren-Peter

    2003-01-01

    Proper function of ion channels is crucial for all living cells. Ion channel dysfunction may lead to a number of diseases, so-called channelopathies, and a number of common diseases, including epilepsy, arrhythmia, and type II diabetes, are primarily treated by drugs that modulate ion channels....... A cornerstone in current drug discovery is high throughput screening assays which allow examination of the activity of specific ion channels though only to a limited extent. Conventional patch clamp remains the sole technique with sufficiently high time resolution and sensitivity required for precise and direct...... characterization of ion channel properties. However, patch clamp is a slow, labor-intensive, and thus expensive, technique. New techniques combining the reliability and high information content of patch clamping with the virtues of high throughput philosophy are emerging and predicted to make a number of ion...

  17. Formulation and Optimization of Multiparticulate Drug Delivery System Approach for High Drug Loading.

    Science.gov (United States)

    Shah, Neha; Mehta, Tejal; Gohel, Mukesh

    2017-08-01

    The aim of the present work was to develop and optimize multiparticulate formulation viz. pellets of naproxen by employing QbD and risk assessment approach. Mixture design with extreme vertices was applied to the formulation with high loading of drug (about 90%) and extrusion-spheronization as a process for manufacturing pellets. Independent variables chosen were level of microcrystalline cellulose (MCC)-X 1 , polyvinylpyrrolidone K-90 (PVP K-90)-X 2 , croscarmellose sodium (CCS)-X 3 , and polacrilin potassium (PP)-X 4 . Dependent variables considered were disintegration time (DT)-Y 1 , sphericity-Y 2 , and percent drug release-Y 3 . The formulation was optimized based on the batches generated by MiniTab 17 software. The batch with maximum composite desirability (0.98) proved to be optimum. From the evaluation of design batches, it was observed that, even in low variation, the excipients affect the pelletization property of the blend and also the final drug release. In conclusion, pellets with high drug loading can be effectively manufactured and optimized systematically using QbD approach.

  18. A facile doxorubicin-dichloroacetate conjugate nanomedicine with high drug loading for safe drug delivery.

    Science.gov (United States)

    Yang, Conglian; Wu, Tingting; Qin, Yuting; Qi, Yan; Sun, Yu; Kong, Miao; Jiang, Xue; Qin, Xianya; Shen, Yaqi; Zhang, Zhiping

    2018-01-01

    Doxorubicin (DOX) is an effective chemotherapeutic agent but severe side effects limit its clinical application. Nanoformulations can reduce the toxicity while still have various limitations, such as complexity, low drug loading capability and excipient related concerns. An amphiphilic conjugate, doxorubicin-dichloroacetate, was synthesized and the corresponding nanoparticles were prepared. The in vitro cytotoxicity and intracellular uptake, in vivo imaging, antitumor effects and systemic toxicities of nanoparticles were carried out to evaluate the therapeutic efficiency of tumor. Doxorubicin-dichloroacetate conjugate can self-assemble into nanoparticles with small amount of DSPE-PEG 2000 , leading to high drug loading (71.8%, w/w) and diminished excipient associated concerns. The nanoparticles exhibited invisible systemic toxicity and high maximum tolerated dose of 75 mg DOX equiv./kg, which was 15-fold higher than that of free DOX. It also showed good tumor targeting capability and enhanced antitumor efficacy in murine melanoma model. This work provides a promising strategy to simplify the drug preparation process, increase drug loading content, reduce systemic toxicity as well as enhance antitumor efficiency.

  19. Solubility of drugs in aqueous polymeric solution: effect of ovalbumin on microencapsulation process.

    Science.gov (United States)

    Aziz, Hesham Abdul; Tan, Yvonne Tze Fung; Peh, Kok Khiang

    2012-03-01

    Microencapsulation of water-soluble drugs using coacervation-phase separation method is very challenging, as these drugs partitioned into the aqueous polymeric solution, resulting in poor drug entrapment. For evaluating the effect of ovalbumin on the microencapsulation of drugs with different solubility, pseudoephedrine HCl, verapamil HCl, propranolol HCl, paracetamol, and curcuminoid were used. In addition, drug mixtures comprising of paracetamol and pseudoephedrine HCl were also studied. The morphology, encapsulation efficiency, particle size, and in vitro release profile were investigated. The results showed that the solubility of the drug determined the ratio of ovalbumin to be used for successful microencapsulation. The optimum ratios of drug, ovalbumin, and gelatin for water-soluble (pseudoephedrine HCl, verapamil HCl, and propranolol HCl), sparingly water-soluble (paracetamol), and water-insoluble (curcuminoid) drugs were found to be 1:1:2, 2:3:5, and 1:3:4. As for the drug mixture, the optimum ratio of drug, ovalbumin, and gelatin was 2:3:5. Encapsulated particles prepared at the optimum ratios showed high yield, drug loading, entrapment efficiency, and sustained release profiles. The solubility of drug affected the particle size of the encapsulated particle. Highly soluble drugs resulted in smaller particle size. In conclusion, addition of ovalbumin circumvented the partitioning effect, leading to the successful microencapsulation of water-soluble drugs.

  20. VOLATILE TRANSPORT INSIDE SUPER-EARTHS BY ENTRAPMENT IN THE WATER-ICE MATRIX

    Energy Technology Data Exchange (ETDEWEB)

    Levi, A.; Podolak, M. [Department of Geophysics and Planetary Science, Tel Aviv University, Tel Aviv 69978 (Israel); Sasselov, D., E-mail: amitlevi.planetphys@gmail.com [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

    2013-05-20

    Whether volatiles can be entrapped in a background matrix composing planetary envelopes and be dragged via convection to the surface is a key question in understanding atmospheric fluxes, cycles, and composition. In this paper, we consider super-Earths with an extensive water mantle (i.e., water planets), and the possibility of entrapment of methane in their extensive water-ice envelopes. We adopt the theory developed by van der Waals and Platteeuw for modeling solid solutions, often used for modeling clathrate hydrates, and modify it in order to estimate the thermodynamic stability field of a new phase called methane filled ice Ih. We find that in comparison to water ice VII the filled ice Ih structure may be stable not only at the high pressures but also at the high temperatures expected at the core-water mantle transition boundary of water planets.

  1. 76 FR 44613 - Designation of Eight Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2011-07-26

    ... OFFICE OF NATIONAL DRUG CONTROL POLICY Designation of Eight Counties as High Intensity Drug Trafficking Areas AGENCY: Office of National Drug Control Policy. ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy has designated eight additional counties as High Intensity Drug...

  2. High resolution visualization and analysis of nasal spray drug delivery.

    Science.gov (United States)

    Inthavong, Kiao; Fung, Man Chiu; Tong, Xuwen; Yang, William; Tu, Jiyuan

    2014-08-01

    Effective nasal drug delivery of new-generation systemic drugs requires efficient devices that can achieve targeted drug delivery. It has been established that droplet size, spray plume, and droplet velocity are major contributors to drug deposition. Continual effort is needed to better understand and characterise the physical mechanisms underpinning droplet formation from nasal spray devices. High speed laser photography combined with an in-house designed automated actuation system, and a highly precise traversing unit, measurements and images magnified in small field-of-view regions within the spray was performed. The qualitative results showed a swirling liquid sheet at the near-nozzle region as the liquid is discharged before ligaments of fluid are separated off the liquid sheet. Droplets are formed and continue to deform as they travel downstream at velocities of up to 20 m/s. Increase in actuation pressure produces more rapid atomization and discharge time where finer droplets are produced. The results suggest that device designs should consider reducing droplet inertia to penetrate the nasal valve region, but find a way to deposit in the main nasal passage and not escape through to the lungs.

  3. Capillary electrophoresis to determine entrapment efficiency of a nanostructured lipid carrier loaded with piroxicam

    Directory of Open Access Journals (Sweden)

    Jessica Otarola

    2015-02-01

    Full Text Available A simple and fast capillary electrophoresis method has been developed to determine the amount of piroxicam loaded in a drug delivery system based on nanostructured lipid carriers (NLCs. The entrapment efficiency of the nanostructured lipid carrier was estimated by measuring the concentration of drug not entrapped in a suspension of NLC. The influence of different parameters on migration times, peak symmetry, efficiency and resolution was studied; these parameters included the pH of the electrophoretic buffer solution and the applied voltage. The piroxicam peak was obtained with a satisfactory resolution. The separation was carried out using a running buffer composed of 50 mM ammonium acetate and 13.75 mM ammonia at pH 9. The optimal voltage was 20 kV and the cartridge temperature was 20 °C. The corresponding calibration curve was linear over the range of 2.7–5.4 µg/mL of NLC suspension. The reproducibility of migration time and peak area were investigated, and the obtained RSD% values (n=5 were 0.99 and 2.13, respectively. Keywords: Capillary electrophoresis, Drug delivery system, Nanostructured lipid carrier, Piroxicam

  4. High throughput miniature drug-screening platform using bioprinting technology

    International Nuclear Information System (INIS)

    Rodríguez-Dévora, Jorge I; Reyna, Daniel; Xu Tao; Zhang Bimeng; Shi Zhidong

    2012-01-01

    In the pharmaceutical industry, new drugs are tested to find appropriate compounds for therapeutic purposes for contemporary diseases. Unfortunately, novel compounds emerge at expensive prices and current target evaluation processes have limited throughput, thus leading to an increase of cost and time for drug development. This work shows the development of the novel inkjet-based deposition method for assembling a miniature drug-screening platform, which can realistically and inexpensively evaluate biochemical reactions in a picoliter-scale volume at a high speed rate. As proof of concept, applying a modified Hewlett Packard model 5360 compact disc printer, green fluorescent protein expressing Escherichia coli cells along with alginate gel solution have been arrayed on a coverslip chip under a repeatable volume of 180% ± 26% picoliters per droplet; subsequently, different antibiotic droplets were patterned on the spots of cells to evaluate the inhibition of bacteria for antibiotic screening. The proposed platform was compared to the current screening process, validating its effectiveness. The viability and basic function of the printed cells were evaluated, resulting in cell viability above 98% and insignificant or no DNA damage to human kidney cells transfected. Based on the reduction of investment and compound volume used by this platform, this technique has the potential to improve the actual drug discovery process at its target evaluation stage. (paper)

  5. Anterior Cutaneous Nerve Entrapment Syndrome in a Pediatric Patient Previously Diagnosed With Functional Abdominal Pain: A Case Report.

    Science.gov (United States)

    DiGiusto, Matthew; Suleman, M-Irfan

    2018-03-23

    Chronic abdominal pain is common in children and adolescents but challenging to diagnose, because practitioners may be concerned about missing serious occult disease. Abdominal wall pain is an often ignored etiology for chronic abdominal pain. Anterior cutaneous nerve entrapment syndrome causes abdominal wall pain but is frequently overlooked. Correctly diagnosing patients with anterior cutaneous nerve entrapment syndrome is important because nerve block interventions are highly successful in the remittance of pain. Here, we present the case of a pediatric patient who received a diagnosis of functional abdominal pain but experienced pain remittance after receiving a trigger-point injection and transverse abdominis plane block.

  6. High HCV seroprevalence and HIV drug use risk behaviors among injection drug users in Pakistan

    Directory of Open Access Journals (Sweden)

    Zafar Tariq

    2006-08-01

    Full Text Available Abstract Introduction HIV and HCV risk behaviors among injection drug users (IDUs in two urban areas in Pakistan were identified. Methods From May to June 2003, 351 IDUs recruited in harm-reduction drop-in centers operated by a national non-governmental organization in Lahore (Punjab province and Quetta (Balochistan province completed an interviewer-administered survey and were tested for HIV and HCV. Multivariable logistic regression identified correlates of seropositivity, stratifying by site. All study participants provided written, informed consent. Results All but two were male; median age was 35 and Discussion Despite no HIV cases, overall HCV prevalence was very high, signaling the potential for a future HIV epidemic among IDUs across Pakistan. Programs to increase needle exchange, drug treatment and HIV and HCV awareness should be implemented immediately.

  7. Changes in entrapped gas content and hydraulic conductivity with pressure.

    Science.gov (United States)

    Marinas, Maricris; Roy, James W; Smith, James E

    2013-01-01

    Water table fluctuations continuously introduce entrapped air bubbles into the otherwise saturated capillary fringe and groundwater zone, which reduces the effective (quasi-saturated) hydraulic conductivity, K(quasi), thus impacting groundwater flow, aquifer recharge and solute and contaminant transport. These entrapped gases will be susceptible to compression or expansion with changes in water pressure, as would be expected with water table (and barometric pressure) fluctuations. Here we undertake laboratory experiments using sand-packed columns to quantify the effect of water table changes of up to 250 cm on the entrapped gas content and the quasi-saturated hydraulic conductivity, and discuss our ability to account for these mechanisms in ground water models. Initial entrapped air contents ranged between 0.080 and 0.158, with a corresponding K(quasi) ranging between 2 and 6 times lower compared to the K(s) value. The application of 250 cm of water pressure caused an 18% to 26% reduction in the entrapped air content, resulting in an increase in K(quasi) by 1.16 to 1.57 times compared to its initial (0 cm water pressure) value. The change in entrapped air content measured at pressure step intervals of 50 cm, was essentially linear, and could be modeled according to the ideal gas law. Meanwhile, the changes in K(quasi) with compression-expansion of the bubbles because of pressure changes could be adequately captured with several current hydraulic conductivity models. © Ground Water 2012 and © Her Majesty the Queen in Right of Canada 2012. Ground Water © 2012, National Ground Water Association.

  8. Lipase entrapment in PVA/Chitosan biodegradable film for reactor coatings

    Energy Technology Data Exchange (ETDEWEB)

    Batista, Karla A. [Departamento de Bioquímica e Biologia Molecular, Laboratório de Química de Proteínas, Universidade Federal de Goiás, Cx. Postal 131, 74001-970, Goiânia, GO (Brazil); Lopes, Flavio Marques [Departamento de Bioquímica e Biologia Molecular, Laboratório de Química de Proteínas, Universidade Federal de Goiás, Cx. Postal 131, 74001-970, Goiânia, GO (Brazil); Unidade Universitária de Ciências Exatas e Tecnológicas, Universidade Estadual de Goiás, Anápolis, GO (Brazil); Yamashita, Fabio [Departamento de Tecnologia de Alimentos e Medicamentos, Laboratório de Tecnologia, Universidade Estadual de Londrina, Cx. Postal 6001, CEP 86051-990, Londrina, PR (Brazil); Fernandes, Kátia Flávia, E-mail: katia@icb.ufg.br [Departamento de Bioquímica e Biologia Molecular, Laboratório de Química de Proteínas, Universidade Federal de Goiás, Cx. Postal 131, 74001-970, Goiânia, GO (Brazil)

    2013-04-01

    This study reports the development and characterization of novel biodegradable film, based on chitosan and polyvinyl alcohol containing lipase entrapped. The films showed a thickness of 70.4 and 79 μm to PVA/Chitosan and PVA/Chitosan/Lipase, respectively. The entrapment of lipase in PVA/Chitosan film resulted in increasing of 69.4% tensile strength (TS), and 52.4% of elongation. SEM images showed the formation of a continuous film, without pores or cracks. The lipase entrapment efficiency was estimated in 92% and the films were repeatedly used for 25 hydrolytic cycles, maintaining 62% of initial activity. The PVA/Chitosan/Lipase film was used for olive oil hydrolysis of high performance. These results indicate that PVA/Chitosan/Lipase is a promising material for biotechnology applications such as triacylglycerol hydrolysis and biodiesel production. - Highlights: ► Development and characterization of PVA/Chitosan biodegradable film ► Lipase immobilization onto PVA/Chitosan film ► PVA/Chitosan/Lipase film for reactor coating ► Olive oil hydrolysis using PVA/Chitosan/Lipase film.

  9. Microbiological and chemical properties of kefir manufactured by entrapped microorganisms isolated from kefir grains.

    Science.gov (United States)

    Chen, T-H; Wang, S-Y; Chen, K-N; Liu, J-R; Chen, M-J

    2009-07-01

    In this study, various yeasts (Kluyveromyces marxianus, Saccharomyces turicensis, Pichia fermentans) and lactic acid bacteria (Lactobacillus kefiranofaciens, Lactobacillus kefiri, Leuconostoc mesenteroides) were entrapped in 2 different microspheres using an entrapment ratio for the strains that was based on the distribution ratio of these organisms in kefir grains. The purpose of this study was to develop a new technique to produce kefir using immobilized starter cultures isolated from kefir grains. An increase in cell counts with fermentation cycles was observed for both the lactic acid bacteria (LAB) and yeasts, whereas the cell counts of kefir grains were very stable during cultivation. Scanning electron microscopy showed that the short-chain lactobacilli and lactococci occupied the surface of the LAB microspheres, whereas the long-chain lactobacilli were inside the microspheres. When the yeasts were analyzed, cells at a high density were entrapped in cracks on the surface and within the microspheres, where they were surrounded by the short-chain lactobacilli. The distribution of the LAB and yeast species in kefir produced from grains and microspheres showed that there was no significant difference between the kefirs produced by the 2 methods; moreover, Leu. mesenteroides and K. marxianus were the predominating microflora in both types of kefir. There was no significant difference in the ethanol and exopolysaccharide contents between the 2 kefirs, although the acidity was different.

  10. Lipase entrapment in PVA/Chitosan biodegradable film for reactor coatings

    International Nuclear Information System (INIS)

    Batista, Karla A.; Lopes, Flavio Marques; Yamashita, Fabio; Fernandes, Kátia Flávia

    2013-01-01

    This study reports the development and characterization of novel biodegradable film, based on chitosan and polyvinyl alcohol containing lipase entrapped. The films showed a thickness of 70.4 and 79 μm to PVA/Chitosan and PVA/Chitosan/Lipase, respectively. The entrapment of lipase in PVA/Chitosan film resulted in increasing of 69.4% tensile strength (TS), and 52.4% of elongation. SEM images showed the formation of a continuous film, without pores or cracks. The lipase entrapment efficiency was estimated in 92% and the films were repeatedly used for 25 hydrolytic cycles, maintaining 62% of initial activity. The PVA/Chitosan/Lipase film was used for olive oil hydrolysis of high performance. These results indicate that PVA/Chitosan/Lipase is a promising material for biotechnology applications such as triacylglycerol hydrolysis and biodiesel production. - Highlights: ► Development and characterization of PVA/Chitosan biodegradable film ► Lipase immobilization onto PVA/Chitosan film ► PVA/Chitosan/Lipase film for reactor coating ► Olive oil hydrolysis using PVA/Chitosan/Lipase film

  11. 75 FR 52780 - Designation of Nine Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2010-08-27

    ... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Nine Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated nine additional counties as High Drug Trafficking Areas pursuant to...

  12. 75 FR 21368 - Designation of Five Counties as High Intensity Drug Trafficking Areas

    Science.gov (United States)

    2010-04-23

    ... EXECUTIVE OFFICE OF THE PRESIDENT Office of National Drug Control Policy Designation of Five Counties as High Intensity Drug Trafficking Areas ACTION: Notice. SUMMARY: The Director of the Office of National Drug Control Policy designated five additional counties as High Drug Trafficking Areas pursuant to...

  13. Air Entrapment and Drop Formation in Piezo Inkjet Printing

    NARCIS (Netherlands)

    van der Bos, J.A.

    2011-01-01

    Piezo drop-on-demand (DOD) inkjet printers are used in an increasing number of applications for their reliable deposition of droplets onto a substrate. Droplets of a few picoliters are ejected from an ink jet nozzle at a frequency of up to 50 kHz. However, entrapment of an air microbubble into the

  14. Entrapment and Escape: Inventional Metaphors in Ronald Reagan's Economic Rhetoric.

    Science.gov (United States)

    Aden, Roger C.

    1989-01-01

    Examines Ronald Reagan's use of inventional metaphors of entrapment and escape, language meshing with the American public's perception of the economy in the early 1980s. Notes that Reagan's reliance on inventional metaphors produced a rigidity in his approach to new situations, ultimately damaging his ability to lead the nation. (MM)

  15. Computer tomographic demonstration of the popliteal artery entrapment syndrome

    International Nuclear Information System (INIS)

    Alder, W.; Zwicker, H.

    1979-01-01

    The popliteal artery entrapment syndrome can be diagnosed by computer tomography with a greater degree of certainty than by angiography. The advantage of computer tomography depends on the simultaneous demonstration of the position of the vessel and of the surrounding muscles and their abnormal situation. (orig.) [de

  16. Debt rescheduling: the economics of entrapment under globalization ...

    African Journals Online (AJOL)

    Being, by definition, the alteration of the terms of repayment of a loan with respect to the grace period permissible, the interest rates chargeable, and the overall maturity period, its adoption and application by Nigeria has not only proved dysfunctional, but also instrumental to debt perpetuation and entrapment. The paper is a ...

  17. Popliteal artery entrapment syndrome in a young girl

    International Nuclear Information System (INIS)

    Haidar, Salwa; Thomas, Karen; Miller, Stephen

    2005-01-01

    Popliteal artery entrapment syndrome (PAES) is well-described in adults, but is an uncommon cause of lower-limb pain in children. We present an 11.5-year-old girl with thrombosed aneurysm of the right popliteal artery, subsequently diagnosed with bilateral type I PAES. Multimodality illustration of the radiological findings is presented. (orig.)

  18. 16 CFR 1211.7 - Inherent entrapment protection requirements.

    Science.gov (United States)

    2010-01-01

    ... from the full upmost position both with and without any external entrapment protection device... that represents the most severe operating condition. Any accessories having an effect on the intended... the requirement. The means supplied to comply with the requirement in paragraph (a) of this section...

  19. 16 CFR 1211.8 - Secondary entrapment protection requirements.

    Science.gov (United States)

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Secondary entrapment protection requirements. 1211.8 Section 1211.8 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY... Engineering Documents, 15 Inverness Way East, Englewood, CO 80112, Telephone (800) 854-7179 or Global...

  20. Direct electrochemistry of hemoglobin entrapped in dextran film on ...

    Indian Academy of Sciences (India)

    Direct electrochemistry of hemoglobin (Hb) entrapped in the dextran (De) film on the surface of a room temperature ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) modified carbon paste electrode (CILE) has been investigated. UV-Vis and FT-IR spectroscopy showed that Hb retained its native ...

  1. Swedish high-school pupils’ attitudes towards drugs in relation to drug usage, impulsiveness and other risk factors

    Directory of Open Access Journals (Sweden)

    Fariba Mousavi

    2014-06-01

    Full Text Available Background. Illicit drug use influences people’s lives and elicits unwanted behaviour. Current research shows that there is an increase in young people’s drug use in Sweden. The aim was to investigate Swedish high-school pupils’ attitudes, impulsiveness and gender differences linked to drug use. Risk and protective factors relative to drug use were also a focus of interest.Method. High school pupils (n = 146 aged 17–21 years, responded to the Adolescent Health and Development Inventory, Barratt Impulsiveness Scale and Knowledge, and the Attitudes and Beliefs. Direct logistic, multiple regression analyses, and Multivariate Analysis of Variance were used to analyze the data.Results. Positive Attitudes towards drugs were predicted by risk factors (odds ratio = 37.31 and gender (odds ratio = .32. Risk factors (odds ratio = 46.89, positive attitudes towards drugs (odds ratio = 4.63, and impulsiveness (odds ratio = 1.11 predicted drug usage. Risk factors dimensions Family, Friends and Individual Characteristic were positively related to impulsiveness among drug users. Moreover, although boys reported using drugs to a greater extent, girls expressed more positive attitude towards drugs and even reported more impulsiveness than boys.Conclusion. This study reinforces the notion that research ought to focus on gender differences relative to pro-drug attitudes along with testing for differences in the predictors of girls’ and boys’ delinquency and impulsiveness. Positive attitudes towards drugs among adolescents seem to be part of a vicious circle including risk factors, such as friendly drug environments (e.g., friends who use drugs and unsupportive family environments, individual characteristics, and impulsiveness.

  2. Evaluation of Gentamicin-Entrapped Solid Lipid Microparticles ...

    African Journals Online (AJOL)

    microbial infections, is limited by poor absorption, low bioavailability ... engineering of lipid drug delivery systems. (LBDDS) ... based SLMs), these problems could be surmounted. ..... addition to the burst effect, may also be related to high rate ...

  3. Drugs for treatment of very high blood pressure during pregnancy.

    Science.gov (United States)

    Duley, Lelia; Meher, Shireen; Jones, Leanne

    2013-07-31

    Very high blood pressure during pregnancy poses a serious threat to women and their babies. The aim of antihypertensive therapy is to lower blood pressure quickly but safety, to avoid complications. Antihypertensive drugs lower blood pressure but their comparative effectiveness and safety, and impact on other substantive outcomes is uncertain. To compare different antihypertensive drugs for very high blood pressure during pregnancy. We searched the Cochrane Pregnancy and Childbirth Group Trials Register (9 January 2013). Studies were randomised trials. Participants were women with severe hypertension during pregnancy. Interventions were comparisons of one antihypertensive drug with another. Two review authors independently assessed trials for inclusion and assessed trial quality. Two review authors extracted data and checked them for accuracy. Thirty-five trials (3573 women) with 15 comparisons were included. Women allocated calcium channel blockers were less likely to have persistent high blood pressure compared to those allocated hydralazine (six trials, 313 women; 8% versus 22%; risk ratio (RR) 0.37, 95% confidence interval (CI) 0.21 to 0.66). Ketanserin was associated with more persistent high blood pressure than hydralazine (three trials, 180 women; 27% versus 6%; RR 4.79, 95% CI 1.95 to 11.73), but fewer side-effects (three trials, 120 women; RR 0.32, 95% CI 0.19 to 0.53) and a lower risk of HELLP (haemolysis, elevated liver enzymes and lowered platelets) syndrome (one trial, 44 women; RR 0.20, 95% CI 0.05 to 0.81).Labetalol was associated with a lower risk of hypotension compared to diazoxide (one trial 90 women; RR 0.06, 95% CI 0.00 to 0.99) and a lower risk of caesarean section (RR 0.43, 95% CI 0.18 to 1.02), although both were borderline for statistical significance.Both nimodipine and magnesium sulphate were associated with a high incidence of persistent high blood pressure, but this risk was lower for nimodipine compared to magnesium sulphate (one trial

  4. Recidivism among High-Risk Drug Felons: A Longitudinal Analysis following Residential Treatment

    Science.gov (United States)

    Belenko, Steven; Foltz, Carol; Lang, Michelle A.; Sung, Hung-En

    2004-01-01

    Recent interest in increasing access to substance abuse treatment for drug-involved offenders has been spurred by concerns over expanding prison and jail populations, high recidivism rates for drug-involved offenders, and the close link between illegal drug use and criminal activity. Chronic untreated drug and alcohol abuse is likely to result in…

  5. Novel furosemide cocrystals and selection of high solubility drug forms.

    Science.gov (United States)

    Goud, N Rajesh; Gangavaram, Swarupa; Suresh, Kuthuru; Pal, Sharmistha; Manjunatha, Sulur G; Nambiar, Sudhir; Nangia, Ashwini

    2012-02-01

    Furosemide was screened in cocrystallization experiments with pharmaceutically acceptable coformer molecules to discover cocrystals of improved physicochemical properties, that is high solubility and good stability. Eight novel equimolar cocrystals of furosemide were obtained by liquid-assisted grinding with (i) caffeine, (ii) urea, (iii) p-aminobenzoic acid, (iv) acetamide, (v) nicotinamide, (vi) isonicotinamide, (vii) adenine, and (viii) cytosine. The product crystalline phases were characterized by powder x-ray diffraction, differential scanning calorimetry, infrared, Raman, near IR, and (13) C solid-state NMR spectroscopy. Furosemide-caffeine was characterized as a neutral cocrystal and furosemide-cytosine an ionic salt by single crystal x-ray diffraction. The stability of furosemide-caffeine, furosemide-adenine, and furosemide-cytosine was comparable to the reference drug in 10% ethanol-water slurry; there was no evidence of dissociation of the cocrystal to furosemide for up to 48 h. The other five cocrystals transformed to furosemide within 24 h. The solubility order for the stable forms is furosemide-cytosine > furosemide-adenine > furosemide-caffeine, and their solubilities are approximately 11-, 7-, and 6-fold higher than furosemide. The dissolution rates of furosemide cocrystals were about two times faster than the pure drug. Three novel furosemide compounds of higher solubility and good phase stability were identified in a solid form screen. Copyright © 2011 Wiley Periodicals, Inc.

  6. Thoracic Nerve Root Entrapment by Intrathecal Catheter Coiling: Case Report and Review of the Literature.

    Science.gov (United States)

    Han, Jing L; Loriaux, Daniel B; Tybout, Caroline; Kinon, Merritt D; Rahimpour, Shervin; Runyon, Scott L; Hopkins, Thomas J; Boortz-Marx, Richard L; Lad, Shivanand P

    2016-03-01

    Intrathecal catheter placement has long-term therapeutic benefits in the management of chronic, intractable pain. Despite the diverse clinical applicability and rising prevalence of implantable drug delivery systems in pain medicine, the spectrum of complications associated with intrathecal catheterization remains largely understudied and underreported in the literature. To report a case of thoracic nerve root entrapment resulting from intrathecal catheter migration. Case report. Inpatient hospital service. A 60-year-old man status post implanted intrathecal (IT) catheter for intractable low back pain secondary to failed back surgery syndrome returned to the operating room for removal of IT pump trial catheter after experiencing relapse of preoperative pain and pump occlusion. Initial attempt at ambulatory removal of the catheter was aborted after the patient reported acute onset of lower extremity radiculopathic pain during the extraction. Noncontrast computed tomography (CT) subsequently revealed that the catheter had ascended and coiled around the T10 nerve root. The patient was taken back to the operating room for removal of the catheter under fluoroscopic guidance, with possible laminectomy for direct visualization. Removal was ultimately achieved with slow continuous tension, with complete resolution of the patient's new radicular symptoms. This report describes a single case report. This case demonstrates that any existing loops in the intrathecal catheter during initial implantation should be immediately re-addressed, as they can precipitate nerve root entrapment and irritation. Reduction of the loop or extrication of the catheter should be attempted under continuous fluoroscopic guidance to prevent further neurosurgical morbidity.

  7. Self-Reported Drug and Alcohol Use and Attitudes toward Drug Testing in High Schools with Random Student Drug Testing

    Science.gov (United States)

    DuPont, Robert L.; Campbell, Michael D.; Campbell, Teresa G.; Shea, Corinne L.; DuPont, Helen S.

    2013-01-01

    Many schools implement random student drug testing (RSDT) programs as a drug prevention strategy. This study analyzes self-report surveys of students in eight secondary schools with well-established RSDT programs, comparing students who understood they were subject to testing and students who understood they were not subject to testing. Students…

  8. Comparative Study between topical applications liposomally entrapped DNA repair enzymes and thymidine dinucleotide as radioprotectors

    International Nuclear Information System (INIS)

    Shabon, M.H.; El-Bedewi, A.F.

    2005-01-01

    The delivery of active agents to the skin by liposome carriers received great interest during the last three decades. This is based on their potential to enclose various types of biological materials and to deliver them to diverse cell types. Recent work suggests that liposomes as vehicles for topical drug delivery may be superior to conventional preparations. Also, topical application of DNA repair enzymes to irradiated skin increases the rate of repair of DNA potentially damaged cells. Moreover, thymidine dinucleotide is a new skin photo-protective agent against non-ionizing radiation through induction of DNA repair. Gamma irradiation can produce DNA damage in human skin. DNA mutations have an important role in the development of skin cancer and precancerous skin lesions. Albino rats were irradiated with Cobalt-60 gamma radiation with different doses (0.5, 1.5, 3 Gy), and were treated by either thymidine dinucleotide or liposomally entrapped DNA repair enzymes topically 24 hours before irradiation. Evaluation was done histopathologically by H and E stain. Computerized image analyzer using Masson's trichrome stain was also done. Gamma radiation produced epidermal thinning and dermal inflammatory cells together with collagen fragmentation and clumping in a dose-dependent manner. Comparing between both thymidine dinucleotide and liposomally entrapped DNA repair enzymes pretreated and irradiated rats. Low dose irradiation (0.5 Gy) together with previous drugs showed preservation of epidermis with no inflammatory cells and also it maintained the normal architecture of collagen bundles. However, they were ineffective with higher doses. In conclusion our results may suggest that the effects of gamma radiation on the skin at low dose could be minimized by the use of these drugs before exposure

  9. Partitioning and interfacial tracers for differentiating NAPL entrapment configuration: column-scale investigation.

    Science.gov (United States)

    Dai, D; Barranco, F T; Illangasekare, T H

    2001-12-15

    Research on the use of partitioning and interfacial tracers has led to the development of techniques for estimating subsurface NAPL amount and NAPL-water interfacial area. Although these techniques have been utilized with some success at field sites, current application is limited largely to NAPL at residual saturation, such as for the case of post-remediation settings where mobile NAPL has been removed through product recovery. The goal of this study was to fundamentally evaluate partitioning and interfacial tracer behavior in controlled column-scale test cells for a range of entrapment configurations varying in NAPL saturation, with the results serving as a determinant of technique efficacy (and design protocol) for use with complexly distributed NAPLs, possibly at high saturation, in heterogeneous aquifers. Representative end members of the range of entrapment configurations observed under conditions of natural heterogeneity (an occurrence with residual NAPL saturation [discontinuous blobs] and an occurrence with high NAPL saturation [continuous free-phase LNAPL lens]) were evaluated. Study results indicated accurate prediction (using measured tracer retardation and equilibrium-based computational techniques) of NAPL amount and NAPL-water interfacial area for the case of residual NAPL saturation. For the high-saturation LNAPL lens, results indicated that NAPL-water interfacial area, but not NAPL amount (underpredicted by 35%), can be reasonably determined using conventional computation techniques. Underprediction of NAPL amount lead to an erroneous prediction of NAPL distribution, as indicated by the NAPL morphology index. In light of these results, careful consideration should be given to technique design and critical assumptions before applying equilibrium-based partitioning tracer methodology to settings where NAPLs are complexly entrapped, such as in naturally heterogeneous subsurface formations.

  10. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Sabine Szunerits

    2018-02-01

    Full Text Available Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs, which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field

  11. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery.

    Science.gov (United States)

    Szunerits, Sabine; Boukherroub, Rabah

    2018-01-01

    Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum , the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section "Frontiers in Bioengineering and Biotechnology," the advances in this field and the handful of

  12. Heat: A Highly Efficient Skin Enhancer for Transdermal Drug Delivery

    Science.gov (United States)

    Szunerits, Sabine; Boukherroub, Rabah

    2018-01-01

    Advances in materials science and bionanotechnology have allowed the refinements of current drug delivery systems, expected to facilitate the development of personalized medicine. While dermatological topical pharmaceutical formulations such as foams, creams, lotions, gels, etc., have been proposed for decades, these systems target mainly skin-based diseases. To treat systemic medical conditions as well as localized problems such as joint or muscle concerns, transdermal delivery systems (TDDSs), which use the skin as the main route of drug delivery, are very appealing. Over the years, these systems have shown to offer important advantages over oral as well as intravenous drug delivery routes. Besides being non-invasive and painless, TDDSs are able to deliver drugs with a short-half-life time more easily and are well adapted to eliminate frequent administrations to maintain constant drug delivery. The possibility of self-administration of a predetermined drug dose at defined time intervals makes it also the most convenient personalized point-of-care approach. The transdermal market still remains limited to a narrow range of drugs. While small and lipophilic drugs have been successfully delivered using TDDSs, this approach fails to deliver therapeutic macromolecules due to size-limited transport across the stratum corneum, the outermost layer of the epidermis. The low permeability of the stratum corneum to water-soluble drugs as well as macromolecules poses important challenges to transdermal administration. To widen the scope of drugs for transdermal delivery, new procedures to enhance skin permeation to hydrophilic drugs and macromolecules are under development. Next to iontophoresis and microneedle-based concepts, thermal-based approaches have shown great promise to enhance transdermal drug delivery of different therapeutics. In this inaugural article for the section “Frontiers in Bioengineering and Biotechnology,” the advances in this field and the handful of

  13. Entrapment of victims of spousal abuse in Ghana

    DEFF Research Database (Denmark)

    Adjei, Stephen Baffour

    2017-01-01

    Drawing on discursive psychology and positioning theory, this study explores the influence of cultural and familial value orientations on battered women’s identity, agency and decision to leave or stay in abusive conjugal relationship in Ghana. Two semi-structured focus group discussions and four...... in-depth personal interviews were conducted with 16 victims of husband-to-wife abuse from rural and urban Ghana. The findings indicate that entrapment of victims of spousal abuse in Ghana reflects their social embeddedness and that battered women’s identities and agency are expressed in the context...... of familial and cultural value orientations. The primacy of family identity and victims’ apparent implicit moral obligation to preserve the social image of their extended family influence their entrapment. Participants’ discursive accounts further suggest that stay/leave decisions of battered women in Ghana...

  14. Poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped trans-cinnamaldehyde and eugenol for antimicrobial delivery applications.

    Science.gov (United States)

    Gomes, Carmen; Moreira, Rosana G; Castell-Perez, Elena

    2011-03-01

    Eugenol and trans-cinnamaldehyde are natural compounds known to be highly effective antimicrobials; however, both are hydrophobic molecules, a limitation to their use within the food industry. The goal of this study was to synthesize spherical poly (DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped eugenol and trans-cinnamaldehyde for future antimicrobial delivery applications. The emulsion evaporation method was used to form the nanoparticles in the presence of poly (vinyl alcohol) (PVA) as a surfactant. The inclusion of antimicrobial compounds into the PLGA nanoparticles was accomplished in the organic phase. Synthesis was followed by ultrafiltration (performed to eliminate the excess of PVA and antimicrobial compound) and freeze-drying. The nanoparticles were characterized by their shape, size, entrapment efficiency, and antimicrobial efficiency. The entrapment efficiency for eugenol and trans-cinnamaldehyde was approximately 98% and 92%, respectively. Controlled release experiments conducted in vitro at 37 °C and 100 rpm for 72 h showed an initial burst followed by a slower rate of release of the antimicrobial entrapped inside the PLGA matrix. All loaded nanoparticles formulations proved to be efficient in inhibiting growth of Salmonella spp. (Gram-negative bacterium) and Listeria spp. (Gram-positive bacterium) with concentrations ranging from 20 to 10 mg/mL. Results suggest that the application of these antimicrobial nanoparticles in food systems may be effective at inhibiting specific pathogens. Nanoencapsulation of lipophilic antimicrobial compounds has great potential for improving the effectiveness and efficiency of delivery in food systems. This study consisted of synthesizing PLGA nanoparticles with entrapped eugenol and trans-cinnamaldehyde. By characterizing these new delivery systems, one can understand the controlled-release mechanism and antimicrobial efficiency that provides a foundation that will enable food manufacturers to design

  15. Nuclear electric quadrupole interactions in liquids entrapped in cavities

    Energy Technology Data Exchange (ETDEWEB)

    Furman, Gregory B., E-mail: gregoryf@bgu.ac.il; Meerovich, Victor M.; Sokolovsky, Vladimir L. [Ben Gurion University of the Negev, Physics Department (Israel)

    2016-12-15

    Liquids entrapped in cavities and containing quadrupole nuclei are considered. The interaction of the quadrupole moment of a nucleus with the electric field gradient is studied. In such a system, molecules are in both rotational and translational Brownian motions which are described by the diffusion equation. Solving this equation, we show that the intra- and intermolecular nuclear quadrupole interactions are averaged to zero in cavities with the size larger than several angstroms.

  16. Formulation of resveratrol entrapped niosomes for topical use.

    Science.gov (United States)

    Pando, Daniel; Matos, María; Gutiérrez, Gemma; Pazos, Carmen

    2015-04-01

    A new approach to the formulation of resveratrol (RSV) entrapped niosomes for topical use is proposed in this work. Niosomes were formulated with Gelot 64 (G64) as surfactant, and two skin-compatible unsaturated fatty acids (oleic and linoleic acids), commonly used in pharmaceutical formulations, as penetration enhancers. Niosomes were prepared by two different methods: a thin film hydration method with minor modifications followed by a sonication stage (TFH-S), and an ethanol injection modified method (EIM). Niosomes prepared with the EIM method were in the range of 299-402 nm, while the TFH-S method produced larger niosomes in the range of 293-496 nm. Moreover, niosomes with higher RSV entrapment efficiency (EE) and better stability were generated by the EIM method. Ex vivo transdermal experiments, carried out in Franz diffusion cells on newborn pig skin, indicated that niosomes prepared by the EIM method were more effective for RSV penetration in epidermis and dermis (EDD), with values up to 21% for both penetration enhancers tested. The EIM method, which yielded the best RSV-entrapped niosomes, seems to be the most suitable for scaling up. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Reappraising entrapment neuropathies--mechanisms, diagnosis and management.

    Science.gov (United States)

    Schmid, Annina B; Nee, Robert J; Coppieters, Michel W

    2013-12-01

    The diagnosis of entrapment neuropathies can be difficult because symptoms and signs often do not follow textbook descriptions and vary significantly between patients with the same diagnosis. Signs and symptoms which spread outside of the innervation territory of the affected nerve or nerve root are common. This Masterclass provides insight into relevant mechanisms that may account for this extraterritorial spread in patients with entrapment neuropathies, with an emphasis on neuroinflammation at the level of the dorsal root ganglia and spinal cord, as well as changes in subcortical and cortical regions. Furthermore, we describe how clinical tests and technical investigations may identify these mechanisms if interpreted in the context of gain or loss of function. The management of neuropathies also remains challenging. Common treatment strategies such as joint mobilisation, neurodynamic exercises, education, and medications are discussed in terms of their potential to influence certain mechanisms at the site of nerve injury or in the central nervous system. The mechanism-oriented approach for this Masterclass seems warranted given the limitations in the current evidence for the diagnosis and management of entrapment neuropathies. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. High-Throughput Screening of Ototoxic and Otoprotective Pharmacological Drugs

    Science.gov (United States)

    Kalinec, Federico

    2005-01-01

    Drug ototoxicity research has relied traditionally on animal models for the discovery and development of therapeutic interventions. More than 50 years of research, however, has delivered few--if any--successful clinical strategies for preventing or ameliorating the ototoxic effects of common pharmacological drugs such as aminoglycoside…

  19. Urging Affordable Access to High-Value Cancer Drugs

    Science.gov (United States)

    This infographic highlights some of the main messages from the President’s Cancer Panel report Promoting Value, Affordability, and Innovation in Cancer Drug Treatment. The graphic includes the panel’s recommendations to maximize the value and affordability of cancer drug treatment.

  20. Drug Use and Military Plans of High School Seniors.

    Science.gov (United States)

    O'Malley, Patrick M.; And Others

    1978-01-01

    Contrary to previous findings, drug use rates were not very different for various categories of prospective military servicemen. Findings suggest that there is currently no selection effect operating such that those who enter all-volunteer military service are more prone to drug abuse than their comparably educated age/sex mates. (Author/WI)

  1. Highly deformable and highly fluid vesicles as potential drug delivery systems: theoretical and practical considerations

    Directory of Open Access Journals (Sweden)

    Romero EL

    2013-08-01

    Full Text Available Eder Lilia Romero, Maria Jose Morilla Nanomedicine Research Program, Department of Science and Technology, National University of Quilmes, Bernal, Buenos Aires, Argentina Abstract: Vesicles that are specifically designed to overcome the stratum corneum barrier in intact skin provide an efficient transdermal (systemic or local drug delivery system. They can be classified into two main groups according to the mechanisms underlying their skin interaction. The first group comprises those possessing highly deformable bilayers, achieved by incorporating edge activators to the bilayers or by mixing with certain hydrophilic solutes. The vesicles of this group act as drug carriers that penetrate across hydrophilic pathways of the intact skin. The second group comprises those possessing highly fluid bilayers, owing to the presence of permeation enhancers. The vesicles of this group can act as carriers of drugs that permeate the skin after the barrier of the stratum corneum is altered because of synergistic action with the permeation enhancers contained in the vesicle structure. We have included a detailed overview of the different mechanisms of skin interaction and discussed the most promising preclinical applications of the last five years of Transfersomes® (IDEA AG, Munich, Germany, ethosomes, and invasomes as carriers of antitumoral and anti-inflammatory drugs applied by the topical route. Keywords: Transfersomes, ethosomes, antitumoral, anti-inflammatory, topical delivery

  2. Deep gluteal syndrome: anatomy, imaging, and management of sciatic nerve entrapments in the subgluteal space

    International Nuclear Information System (INIS)

    Hernando, Moises Fernandez; Cerezal, Luis; Perez-Carro, Luis; Abascal, Faustino; Canga, Ana

    2015-01-01

    Deep gluteal syndrome (DGS) is an underdiagnosed entity characterized by pain and/or dysesthesias in the buttock area, hip or posterior thigh and/or radicular pain due to a non-discogenic sciatic nerve entrapment in the subgluteal space. Multiple pathologies have been incorporated in this all-included ''piriformis syndrome,'' a term that has nothing to do with the presence of fibrous bands, obturator internus/gemellus syndrome, quadratus femoris/ischiofemoral pathology, hamstring conditions, gluteal disorders and orthopedic causes. The concept of fibrous bands playing a role in causing symptoms related to sciatic nerve mobility and entrapment represents a radical change in the current diagnosis of and therapeutic approach to DGS. The development of periarticular hip endoscopy has led to an understanding of the pathophysiological mechanisms underlying piriformis syndrome, which has supported its further classification. A broad spectrum of known pathologies may be located nonspecifically in the subgluteal space and can therefore also trigger DGS. These can be classified as traumatic, iatrogenic, inflammatory/infectious, vascular, gynecologic and tumors/pseudo-tumors. Because of the ever-increasing use of advanced magnetic resonance neurography (MRN) techniques and the excellent outcomes of the new endoscopic treatment, radiologists must be aware of the anatomy and pathologic conditions of this space. MR imaging is the diagnostic procedure of choice for assessing DGS and may substantially influence the management of these patients. The infiltration test not only has a high diagnostic but also a therapeutic value. This article describes the subgluteal space anatomy, reviews known and new etiologies of DGS, and assesses the role of the radiologist in the diagnosis, treatment and postoperative evaluation of sciatic nerve entrapments, with emphasis on MR imaging and endoscopic correlation. (orig.)

  3. Deep gluteal syndrome: anatomy, imaging, and management of sciatic nerve entrapments in the subgluteal space

    Energy Technology Data Exchange (ETDEWEB)

    Hernando, Moises Fernandez; Cerezal, Luis; Perez-Carro, Luis; Abascal, Faustino; Canga, Ana [Diagnostico Medico Cantabria (DMC), Department of Radiology, Santander, Cantabria (Spain); Valdecilla University Hospital, Orthopedic Surgery Department Clinica Mompia (L.P.C.), Santander, Cantabria (Spain); Valdecilla University Hospital, Department of Radiology, Santander, Cantabria (Spain)

    2015-03-05

    Deep gluteal syndrome (DGS) is an underdiagnosed entity characterized by pain and/or dysesthesias in the buttock area, hip or posterior thigh and/or radicular pain due to a non-discogenic sciatic nerve entrapment in the subgluteal space. Multiple pathologies have been incorporated in this all-included ''piriformis syndrome,'' a term that has nothing to do with the presence of fibrous bands, obturator internus/gemellus syndrome, quadratus femoris/ischiofemoral pathology, hamstring conditions, gluteal disorders and orthopedic causes. The concept of fibrous bands playing a role in causing symptoms related to sciatic nerve mobility and entrapment represents a radical change in the current diagnosis of and therapeutic approach to DGS. The development of periarticular hip endoscopy has led to an understanding of the pathophysiological mechanisms underlying piriformis syndrome, which has supported its further classification. A broad spectrum of known pathologies may be located nonspecifically in the subgluteal space and can therefore also trigger DGS. These can be classified as traumatic, iatrogenic, inflammatory/infectious, vascular, gynecologic and tumors/pseudo-tumors. Because of the ever-increasing use of advanced magnetic resonance neurography (MRN) techniques and the excellent outcomes of the new endoscopic treatment, radiologists must be aware of the anatomy and pathologic conditions of this space. MR imaging is the diagnostic procedure of choice for assessing DGS and may substantially influence the management of these patients. The infiltration test not only has a high diagnostic but also a therapeutic value. This article describes the subgluteal space anatomy, reviews known and new etiologies of DGS, and assesses the role of the radiologist in the diagnosis, treatment and postoperative evaluation of sciatic nerve entrapments, with emphasis on MR imaging and endoscopic correlation. (orig.)

  4. Entrapment of curcumin into monoolein-based liquid crystalline nanoparticle dispersion for enhancement of stability and anticancer activity

    Science.gov (United States)

    Baskaran, Rengarajan; Madheswaran, Thiagarajan; Sundaramoorthy, Pasupathi; Kim, Hwan Mook; Yoo, Bong Kyu

    2014-01-01

    Despite the promising anticancer potential of curcumin, its therapeutic application has been limited, owing to its poor solubility, bioavailability, and chemical fragility. Therefore, various formulation approaches have been attempted to address these problems. In this study, we entrapped curcumin into monoolein (MO)-based liquid crystalline nanoparticles (LCNs) and evaluated the physicochemical properties and anticancer activity of the LCN dispersion. The results revealed that particles in the curcumin-loaded LCN dispersion were discrete and monodispersed, and that the entrapment efficiency was almost 100%. The stability of curcumin in the dispersion was surprisingly enhanced (about 75% of the curcumin survived after 45 days of storage at 40°C), and the in vitro release of curcumin was sustained (10% or less over 15 days). Fluorescence-activated cell sorting (FACS) analysis using a human colon cancer cell line (HCT116) exhibited 99.1% fluorescence gating for 5 μM curcumin-loaded LCN dispersion compared to 1.36% for the same concentration of the drug in dimethyl sulfoxide (DMSO), indicating markedly enhanced cellular uptake. Consistent with the enhanced cellular uptake of curcumin-loaded LCNs, anticancer activity and cell cycle studies demonstrated apoptosis induction when the cells were treated with the LCN dispersion; however, there was neither noticeable cell death nor significant changes in the cell cycle for the same concentration of the drug in DMSO. In conclusion, entrapping curcumin into MO-based LCNs may provide, in the future, a strategy for overcoming the hurdles associated with both the stability and cellular uptake issues of the drug in the treatment of various cancers. PMID:25061290

  5. Entrapment of curcumin into monoolein-based liquid crystalline nanoparticle dispersion for enhancement of stability and anticancer activity

    Directory of Open Access Journals (Sweden)

    Baskaran R

    2014-06-01

    Full Text Available Rengarajan Baskaran,1 Thiagarajan Madheswaran,2 Pasupathi Sundaramoorthy,1 Hwan Mook Kim,1 Bong Kyu Yoo1 1College of Pharmacy, Gachon University, Incheon, South Korea; 2College of Pharmacy Yeungnam University, Gyeongsan, South Korea Abstract: Despite the promising anticancer potential of curcumin, its therapeutic application has been limited, owing to its poor solubility, bioavailability, and chemical fragility. Therefore, various formulation approaches have been attempted to address these problems. In this study, we entrapped curcumin into monoolein (MO-based liquid crystalline nanoparticles (LCNs and evaluated the physicochemical properties and anticancer activity of the LCN dispersion. The results revealed that particles in the curcumin-loaded LCN dispersion were discrete and monodispersed, and that the entrapment efficiency was almost 100%. The stability of curcumin in the dispersion was surprisingly enhanced (about 75% of the curcumin survived after 45 days of storage at 40°C, and the in vitro release of curcumin was sustained (10% or less over 15 days. Fluorescence-activated cell sorting (FACS analysis using a human colon cancer cell line (HCT116 exhibited 99.1% fluorescence gating for 5 µM curcumin-loaded LCN dispersion compared to 1.36% for the same concentration of the drug in dimethyl sulfoxide (DMSO, indicating markedly enhanced cellular uptake. Consistent with the enhanced cellular uptake of curcumin-loaded LCNs, anticancer activity and cell cycle studies demonstrated apoptosis induction when the cells were treated with the LCN dispersion; however, there was neither noticeable cell death nor significant changes in the cell cycle for the same concentration of the drug in DMSO. In conclusion, entrapping curcumin into MO-based LCNs may provide, in the future, a strategy for overcoming the hurdles associated with both the stability and cellular uptake issues of the drug in the treatment of various cancers. Keywords: liquid

  6. Highlights from Drug Use Among American High School Students 1975-1977.

    Science.gov (United States)

    Johnston, Lloyd D.; And Others

    The current prevalence of drug use among American high school seniors and the trends in use since 1975 are the two major topics treated. Also reported are prevailing attitudes and beliefs among seniors concerning various types of drug use. Eleven separate classes of drugs are distinguished: marihuana (including hashish), inhalants, hallucinogens,…

  7. Increased Risk of Drug-Induced Hyponatremia during High Temperatures

    Directory of Open Access Journals (Sweden)

    Anna K Jönsson

    2017-07-01

    Full Text Available Purpose: To investigate the relationship between outdoor temperature in Sweden and the reporting of drug-induced hyponatremia to the Medical Products Agency (MPA. Methods: All individual adverse drug reactions (ADR reported to MPA from 1 January 2010 to 31 October 2013 of suspected drug-induced hyponatremia and random controls were identified. Reports where the ADR had been assessed as having at least a possible relation to the suspected drug were included. Information on administered drugs, onset date, causality assessment, sodium levels, and the geographical origin of the reports was extracted. A case-crossover design was used to ascertain the association between heat exposure and drug-induced hyponatremia at the individual level, while linear regression was used to study its relationship to sodium concentration in blood. Temperature exposure data were obtained from the nearest observation station to the reported cases. Results: During the study period, 280 reports of hyponatremia were identified. More cases of drug-induced hyponatremia were reported in the warmer season, with a peak in June, while other ADRs showed an opposite annual pattern. The distributed lag non-linear model indicated an increasing odds ratio (OR with increasing temperature in the warm season with a highest odds ratio, with delays of 1–5 days after heat exposure. A cumulative OR for a lag time of 1 to 3 days was estimated at 2.21 at an average daily temperature of 20 °C. The change in sodium per 1 °C increase in temperature was estimated to be −0.37 mmol/L (95% CI: −0.02, −0.72. Conclusions: Warm weather appears to increase the risk of drug-induced hyponatremia

  8. A directional entrapment modification on the polyethylene surface by the amphiphilic modifier of stearyl-alcohol poly(ethylene oxide) ether

    Science.gov (United States)

    Lu, Qiang; Chen, Yi; Huang, Juexin; Huang, Jian; Wang, Xiaolin; Yao, Jiaying

    2018-05-01

    A novel entrapment modification method involving directional implantation of the amphiphilic modifier of stearyl-alcohol poly(ethylene oxide) ether (AEO) into the high-density polyethylene (HDPE) surface is proposed. This modification technique allows the AEO modifier to be able to spontaneously attain and subsequently penetrate into the swollen HDPE surface with its hydrophobic stearyl segment, while its hydrophilic poly(ethylene oxide) (PEO) segment spontaneously points to water. The AEO modifier with a HLB number below 8.7 was proved appropriate for the directional entrapment, Nevertheless, AEOs with larger HLB numbers were also effective modifiers in the presence of salt additives. In addition, a larger and hydrophobic micelle, induced respectively by the AEO concentration above 1.3 × 10-2 mol/L and the entrapping temperature above the cloud point of AEO, could lead to a sharp contact angle decline of the modified surface. Finally, a hydrophilic HDPE surface with the modifier coverage of 38.9% was reached by the directional entrapment method, which is far larger than that of 19.2% by the traditional entrapment method.

  9. Development of a glucose oxidase-based biocatalyst adopting both physical entrapment and crosslinking, and its use in biofuel cells

    Science.gov (United States)

    Chung, Yongjin; Ahn, Yeonjoo; Christwardana, Marcelinus; Kim, Hansung; Kwon, Yongchai

    2016-04-01

    New enzymatic catalysts prepared using physical entrapment and chemical bonding were used as anodic catalysts to enhance the performance of enzymatic biofuel cells (EBCs). For estimating the physical entrapment effect, the best glucose oxidase (GOx) concentration immobilized on polyethyleneimine (PEI) and carbon nanotube (CNT) (GOx/PEI/CNT) was determined, while for inspecting the chemical bonding effect, terephthalaldehyde (TPA) and glutaraldehyde (GA) crosslinkers were employed. According to the enzyme activity and XPS measurements, when the GOx concentration is 4 mg mL-1, they are most effectively immobilized (via the physical entrapment effect) and TPA-crosslinked GOx/PEI/CNT(TPA/[GOx/PEI/CNT]) forms π conjugated bonds via chemical bonding, inducing the promotion of electron transfer by delocalization of electrons. Due to the optimized GOx concentration and π conjugated bonds, TPA/[GOx/PEI/CNT], including 4 mg mL-1 GOx displays a high electron transfer rate, followed by excellent catalytic activity and EBC performance.New enzymatic catalysts prepared using physical entrapment and chemical bonding were used as anodic catalysts to enhance the performance of enzymatic biofuel cells (EBCs). For estimating the physical entrapment effect, the best glucose oxidase (GOx) concentration immobilized on polyethyleneimine (PEI) and carbon nanotube (CNT) (GOx/PEI/CNT) was determined, while for inspecting the chemical bonding effect, terephthalaldehyde (TPA) and glutaraldehyde (GA) crosslinkers were employed. According to the enzyme activity and XPS measurements, when the GOx concentration is 4 mg mL-1, they are most effectively immobilized (via the physical entrapment effect) and TPA-crosslinked GOx/PEI/CNT(TPA/[GOx/PEI/CNT]) forms π conjugated bonds via chemical bonding, inducing the promotion of electron transfer by delocalization of electrons. Due to the optimized GOx concentration and π conjugated bonds, TPA/[GOx/PEI/CNT], including 4 mg mL-1 GOx displays a high

  10. Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids.

    Science.gov (United States)

    He, Susu; Chandler, Michael; Varani, Alessandro M; Hickman, Alison B; Dekker, John P; Dyda, Fred

    2016-12-06

    The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content) of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE) from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance. The spread of antibiotic resistance among Gram-negative bacteria is a serious public health threat, as it can critically limit the types of drugs that can be used to treat infected patients. In particular, carbapenem-resistant members of the Enterobacteriaceae family are responsible for a significant and growing burden of morbidity and mortality. Here, we report on the mechanisms underlying the evolution of several plasmids carried by previously sequenced clinical Enterobacteriaceae isolates from the National Institutes of Health Clinical Center (NIH CC). Our ability to track genetic rearrangements that occurred within resistance plasmids was dependent on accurate annotation of the mobile genetic elements within the plasmids, which was greatly aided by access to long-read DNA sequencing data and knowledge of their mechanisms. Mobile genetic elements such as

  11. Reversible entrapment of plasmid deoxyribonucleic acid on different chromatographic supports.

    Science.gov (United States)

    Gabor, Boštjan; Černigoj, Urh; Barut, Miloš; Štrancar, Aleš

    2013-10-11

    HPLC based analytical assay is a powerful technique that can be used to efficiently monitor plasmid DNA (pDNA) purity and quantity throughout the entire purification process. Anion exchange monolithic and non-porous particle based stationary phases were used to study the recovery of the different pDNA isoforms from the analytical column. Three differently sized pDNA molecules of 3.0kbp, 5.2kbp and 14.0kbp were used. Plasmid DNA was injected onto columns under the binding conditions and the separation of the isoforms took place by increasing the ionic strength of the elution buffer. While there was no substantial decrease of the recovered supercoiled and linear isoforms of the pDNA with the increase of the plasmid size and with the increase of the flow rate (recoveries in all cases larger than 75%), a pronounced decrease of the oc isoform recovery was observed. The entrapment of the oc pDNA isoform occurred under non-binding conditions as well. The partial oc isoform elution from the column could be achieved by decreasing the flow rate of the elution mobile phase. The results suggested a reversible entrapment of the oc isoform in the restrictions within the pores of the monolithic material as well as within the intra-particle space of the non-porous particles. This phenomenon was observed on both types of the stationary phase morphologies and could only be connected to the size of a void space through which the pDNA needs to migrate. A prediction of reversible pDNA entrapment was successfully estimated with the calculation of Peclet numbers, Pe, which defines the ratio between a convective and diffusive mass transport. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Characterization of a sol-gel-entrapped artificial receptor

    Science.gov (United States)

    Dunbar, Richard A.; Narang, Upvan; Prasad, Paras N.; Bright, Frank V.

    1993-04-01

    We report on the development, characterization, and photophysics of a new fiber-optic-based sensor which uses a sol-gel entrapped recognition element. The recognition element is modified (beta) -cyclodextrin to which we have added a short tether (glycine) and a fluorophore (dansyl). This recognition element forms an intramolecular complex, and the dansyl group can include within the cyclodextrin cavity. Non-fluorescent analytes, that bind to the cyclodextrin cavity, can effectively displace the included dansyl group and result in a measurable change in signal. We report on the detection limits, dynamic range, and photophysics (i.e., transduction mechanism) of this new sensor.

  13. The role of diagnostic radiology in compressive and entrapment neuropathies

    International Nuclear Information System (INIS)

    Spratt, J.D.; Stanley, A.J.; Hide, I.G.; Campbell, R.S.D.; Grainger, A.J.

    2002-01-01

    Diagnostic imaging is increasingly being utilised to aid the diagnosis of compression and entrapment neuropathies. Cross-sectional imaging, primarily ultrasound and magnetic resonance imaging, can provide exquisite anatomical detail of peripheral nerves and the changes that may occur as a result of compression. Imaging can provide a useful diagnostic aid to clinicians, which may supplement clinical evaluation, and may eventually provide an alternative to other diagnostic techniques such as nerve conduction studies. This article describes the abnormalities that may be demonstrated by current imaging techniques, and critically analyses the impact of imaging in diagnosis of peripheral compressive neuropathy. (orig.)

  14. The role of diagnostic radiology in compressive and entrapment neuropathies

    Energy Technology Data Exchange (ETDEWEB)

    Spratt, J.D.; Stanley, A.J.; Hide, I.G.; Campbell, R.S.D. [Department of Radiology, James Cook University Hospital, Middlesbrough, TS4 3BW (United Kingdom); Grainger, A.J. [Department of Radiology, Leeds General Infirmary, Leeds (United Kingdom)

    2002-09-01

    Diagnostic imaging is increasingly being utilised to aid the diagnosis of compression and entrapment neuropathies. Cross-sectional imaging, primarily ultrasound and magnetic resonance imaging, can provide exquisite anatomical detail of peripheral nerves and the changes that may occur as a result of compression. Imaging can provide a useful diagnostic aid to clinicians, which may supplement clinical evaluation, and may eventually provide an alternative to other diagnostic techniques such as nerve conduction studies. This article describes the abnormalities that may be demonstrated by current imaging techniques, and critically analyses the impact of imaging in diagnosis of peripheral compressive neuropathy. (orig.)

  15. Towards successful bioaugmentation with entrapped cells as a soil remediation technology

    DEFF Research Database (Denmark)

    Owsianiak, Mikolaj; Dechesne, Arnaud; Binning, Philip John

    2010-01-01

    Soil remediation technologies are proposed that rely on inoculation with degrading microorganisms entrapped in protective carriers. A mathematical model developed to model entrapped cell bioaugmentation describes the 3-D diffusion-driven mass transfer of benzoate, and its mineralization...... but is restricted in dry conditions, as confirmed by performing cell counts. This highlights the potential of entrapped cells when they act as seeds for soil colonization....

  16. Amphotericin-B entrapped lecithin/chitosan nanoparticles for prolonged ocular application.

    Science.gov (United States)

    Chhonker, Yashpal S; Prasad, Yarra Durga; Chandasana, Hardik; Vishvkarma, Akhilesh; Mitra, Kalyan; Shukla, Praveen K; Bhatta, Rabi S

    2015-01-01

    Fungal keratitis is the major cause of vision loss worldwide. Amphotericin-B is considered as the drug of choice for fungal infections. However, its use in ophthalmic drug delivery is limited by the low precorneal residence at ocular surface as a result of blinking reflex, tear turnover and nasopharyngeal drainage. We report Amphotericin-B loaded lecithin/chitosan nanoparticles for prolonged ocular application. The prepared nanoparticles were in the size range of 161.9-230.5 nm, entrapment efficiency of 70-75%, theoretical drug loading of 5.71% with positive zeta potential of 26.6-38.3 mV. As demonstrated by antifungal susceptibility against Candida albicans and Aspergillus fumigatus, nanoparticles were more effective than marketed formulation. They exhibited pronounced mucoadhesive properties. In-vivo pharmacokinetic studies in New Zealand albino rabbit eyes indicated improved bioavailablity (∼ 2.04 fold) and precorneal residence time (∼ 3.36 fold) by nanoparticles prepared from low molecular weight chitosan as compared with marketed formulation. Copyright © 2014. Published by Elsevier B.V.

  17. Drug combination may be highly effective in recurrent ovarian cancer

    Science.gov (United States)

    Significant improvement with the use of a combination drug therapy for recurrent ovarian cancer was reported at the annual meeting of the American Society of Clinical Oncology meeting in Chicago. The trial compared the activity of a combination of the dru

  18. MR imaging and MR angiography in popliteal artery entrapment syndrome

    International Nuclear Information System (INIS)

    Atilla, S.; Akpek, S.; Yuecel, C.; Tali, E.T.; Isik, S.; Ilgit, E.T.

    1998-01-01

    Popliteal artery entrapment (PAE) syndrome is an uncommon congenital anomaly seen in young adults causing ischemic symptoms in the lower extremities. It is the result of various types of anomalous relationships between the popliteal artery and the neighboring muscular structures. The purpose of this study was to define the role of MR imaging combined with MR angiography in the diagnosis of PAE cases. Four cases with segmental occlusion and medial displacement of popliteal artery in digital subtraction angiography (DSA) examinations were diagnosed as PAE syndrome by MR imaging and MR angiography. The DSA and MRA images are compared. All of the cases showed various degrees of abnormal intercondylar insertion of the medial head of the gastrocnemius muscle. The MR images showed detailed anatomy of the region revealing the cause of the arterial entrapment. Subclassification of the cases were done and fat tissue filling the normal localization of the muscle was evaluated. The DSA and MRA images demonstrated the length and localization of the occluded segment and collateral vascular developments equally. It is concluded that angiographic evaluation alone in PAE syndrome might result in overlooking the underlying cause of the arterial occlusion, which in turn leads to unsuccessful therapy procedures such as balloon angioplasty. Magnetic resonance imaging combined with MR angiography demonstrates both the vascular anatomy and the variations in the muscular structures in the popliteal fossa successfully, and this combination seems to be the most effective way of evaluating young adults with ischemic symptoms suggesting PAE syndrome. (orig.)

  19. Dynamics of the central entrapped bubble during drop impact

    Science.gov (United States)

    Jian, Zhen; Channa, Murad Ali; Thoraval, Marie-Jean

    2017-11-01

    When a drop impacts onto a liquid surface, it entraps a thin central air disk. The air is then brought towards the axis of symmetry by surface tension. This contraction dynamics is very challenging to capture, due to the small length scales (a few micrometers thin air disk) and time scales (contracting in a few hundred microseconds). We use the open source two-phase flow codes Gerris and Basilisk to study this air entrapment phenomenon. The effects of liquid properties such as viscosity and surface tension, and of the impact velocity were investigated. We focus on the morphology of the contracting air disk. The bubble is expected to contract into a single spherical bubble. However, in some cases, the air can be stretched vertically by the liquid inertia and split into two smaller bubbles. The convergence of capillary waves on the air disk towards the axis of symmetry can also make it rupture at the center, thus forming a toroidal bubble. In other cases, vorticity shedding can deform the contracting bubble, leading to more complex structures. A parameter space analysis based on the Reynolds and Weber numbers was then done to classify the different regimes and explain the transitions. Full affiliation:State Key Laboratory for Strength and Vibration of Mechanical Structures,Shaanxi Key Laboratory of Environment and Control for Flight Vehicle,International Center for Applied Mechanics,School of Aerospace,Xi'an Jiaotong University.

  20. Silica Sol-Gel Entrapment of the Enzyme Chloro peroxidase

    International Nuclear Information System (INIS)

    Le, T.; Chan, S.; Ebaid, B.; Sommerhalter, M.

    2015-01-01

    The enzyme chloro peroxidase (CPO) was immobilized in silica sol-gel beads prepared from tetramethoxysilane. The average pore diameter of the silica host structure (∼3 nm) was smaller than the globular CPO diameter (∼6 nm) and the enzyme remained entrapped after sol-gel maturation. The catalytic performance of the entrapped enzyme was assessed via the pyrogallol peroxidation reaction. Sol-gel beads loaded with 4 μg CPO per mL sol solution reached 9-12% relative activity compared to free CPO in solution. Enzyme kinetic analysis revealed a decrease in K_cat but no changes in K_M or K_I . Product release or enzyme damage might thus limit catalytic performance. Yet circular dichroism and visible absorption spectra of transparent CPO sol-gel sheets did not indicate enzyme damage. Activity decline due to methanol exposure was shown to be reversible in solution. To improve catalytic performance the sol-gel protocol was modified. The incorporation of 5, 20, or 40% methyltrimethoxysilane resulted in more brittle sol-gel beads but the catalytic performance increased to 14% relative to free CPO in solution. The use of more acidic casting buffers (ph 4.5 or 5.5 instead of 6.5) resulted in a more porous silica host reaching up to 18% relative activity

  1. Bioerodible drug/eluting stent coating with highly controllable drug release rate and excellent vascular biocompatibility

    Czech Academy of Sciences Publication Activity Database

    Rypáček, František; Mulinková, Katarína; Bernátková, Markéta; Machová, Luďka; Lapčíková, Monika; Otsuka, Y.; Robinson, K. A.; Mulkey, S. P.; Baranowski, C.; Zablocki, J.; Blackburn, B. K.; Chronos, N.

    2005-01-01

    Roč. 96, 7A (2005), 209H-210H ISSN 0002-9149. [Annual Conference of Transcathetral Cardiovascular Therapeutics /17./. Washington, 16.10.2005-21.10.2005] R&D Projects: GA AV ČR IAA4050202 Institutional research plan: CEZ:AV0Z40500505 Keywords : drug delivery * polymer coating * stent Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.059, year: 2005

  2. Primary drug resistance in a region with high burden of tuberculosis. A critical problem.

    Science.gov (United States)

    Villa-Rosas, Cecilia; Laniado-Laborín, Rafael; Oceguera-Palao, Lorena

    2015-01-01

    To determine rates of drug resistance in new cases of pulmonary tuberculosis in a region with a high burden of the disease. New case suspects were referred for drug susceptibility testing. 28.9% of new cases were resistant to at least one first line drug; 3.9% had a multidrug-resistant strain, 15.6% a monoresistant strain and 9.4% a polyresistant strain. Our rate of drug resistant tuberculosis in new cases is very high; this has important clinical implications, since even monoresistance can have a negative impact on the outcome of new cases treated empirically with a six month regimen.

  3. Effects of process variables on micromeritic properties and drug release of non-degradable microparticles

    Directory of Open Access Journals (Sweden)

    Mitra Jelvehgari

    2011-06-01

    Full Text Available Introduction: The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Methods: Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR, differential scanning colorimetry (DSC and scanning electron microscopy (SEM. The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Results: Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100 (1:6 showed 60-75% of entrapment and mean particle size 205.93-352.76 µm. The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1 resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. Conclusion: The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model.

  4. Effects of process variables on micromeritic properties and drug release of non-degradable microparticles.

    Science.gov (United States)

    Jelvehgari, Mitra; Barar, Jaleh; Nokhodchi, Ali; Shadrou, Sanam; Valizadeh, Hadi

    2011-01-01

    The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100(1:6) showed 60-75% of entrapment and mean particle size 205.93-352.76 μm.The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model.

  5. High-resolution two-dimensional liquid chromatography analysis of key linker drug intermediate used in antibody drug conjugates.

    Science.gov (United States)

    Venkatramani, C J; Huang, Shu Rong; Al-Sayah, Mohammad; Patel, Ila; Wigman, Larry

    2017-10-27

    In this manuscript, the application of high-resolution sampling (HRS) two-dimensional liquid chromatography (2D-LC) in the detailed analysis of key linker drug intermediate is presented. Using HRS, selected regions of the primary column eluent were transferred to a secondary column with fidelity enabling qualitative and quantitative analysis of linker drugs. The primary column purity of linker drug intermediate ranged from 88.9% to 94.5% and the secondary column purity ranged from 99.6% to 99.9%, showing lot-to-lot variability, significant differences between the three lots, and substantiating the synthetic and analytical challenges of ADCs. Over 15 impurities co-eluting with the linker drug intermediate in the primary dimension were resolved in the secondary dimension. The concentrations of most of these impurities were over three orders of magnitude lower than the linker drug. Effective peak focusing and high-speed secondary column analysis resulted in sharp peaks in the secondary dimension, improving the signal-to-noise ratios. The sensitivity of 2D-LC separation was over five fold better than conventional HPLC separation. The limit of quantitation (LOQ) was less than 0.01%. Many peaks originating from primary dimension were resolved into multiple components in the complementary secondary dimension, demonstrating the complexity of these samples. The 2D-LC was highly reproducible, showing good precision between runs with%RSD of peak areas less than 0.1 for the main component. The absolute difference in the peak areas of impurities less than 0.1% were within ±0.01% and for impurities in the range of 0.1%-0.3%, the absolute difference were ±0.02%, which are comparable to 1D-LC. The overall purity of the linker drug intermediate was determined from the product of primary and secondary column purity (HPLC Purity=%peak area of main component in the primary dimension×%peak area of main component in the secondary dimension). Additionally, the 2D-LC separation enables

  6. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

    Science.gov (United States)

    Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

    2014-01-01

    During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

  7. Entrapment of laurel lipase in chitosan hydrogel beads.

    Science.gov (United States)

    Yagar, Hulya; Balkan, Ugur

    2017-08-01

    Laurel seed lipase was entrapped within chitosan beads with ionotropic gelatin method using tripolyphosphate (TPP) as multivalent covalent counter ion. Immobilization yield was 78%. First, optimum immobilization conditions were determined, and morphology of chitosan beads was characterized by scanning electron microscopy. Optimum pH and temperature were evaluated as 6.0 and 40 °C, respectively. The immobilized beads saved about 55% of its activities at 60° while saved about 32% at 70 °C for 30 min. V max /K m values were determined as 31.75 and 2.87 using olive oil as substrate for immobilized beads and free enzyme, respectively. Immobilized beads showed the activities during 30 days at +4 °C.

  8. Entrapment and Enmeshment Schemes Used by Sex Traffickers.

    Science.gov (United States)

    Reid, Joan A

    2016-09-01

    Emerging research suggests that sex traffickers/pimps control the majority of trafficked girls in the United States. The youthfulness of these victims and their lack of psychosocial maturity severely diminish their ability to detect exploitative motives or withstand manipulation of traffickers. A review of 43 cases of sexually exploited girls involving non-relative traffickers and 10 semi-structured interviews with social service providers revealed numerous scripts and schemes used by sex traffickers to entrap and entangle victims including boyfriend/lover scripts, ruses involving debt bondage, friendship or faux-family scripts, threats of forced abortion or to take away children, and coerced co-offending. These findings inform potential prevention efforts and highlight the need for multi-systemic, victim-centered approaches to intervention. © The Author(s) 2014.

  9. Ulnar nerve entrapment in Guyon's canal due to a lipoma.

    Science.gov (United States)

    Ozdemir, O; Calisaneller, T; Gerilmez, A; Gulsen, S; Altinors, N

    2010-09-01

    Guyon's canal syndrome is an ulnar nerve entrapment at the wrist or palm that can cause motor, sensory or combined motor and sensory loss due to various factors . In this report, we presented a 66-year-old man admitted to our clinic with a history of intermittent pain in the left palm and numbness in 4th and 5th finger for two years. His neurological examination revealed a sensory impairment in the right fifth finger. Also, physical examination displayed a subcutaneous mobile soft tissue in ulnar side of the wrist. Electromyographic examination confirmed the diagnosis of type-1 Guyon's canal syndrome. Under axillary blockage, a lipoma compressing the ulnar nerve was excised totally and ulnar nerve was decompressed. The symptoms were improved after the surgery and patient was symptom free on 3rd postoperative week.

  10. THE EXPERIENCE OF ‘ENTRAPPED GRIEF’ FOLLOWING TRAUMATIC ABORTION

    Directory of Open Access Journals (Sweden)

    Linda Finlay

    2015-12-01

    Full Text Available Some abortions can result in prolonged, complex grief reactions where the effects endure in problematic ways. Research findings suggest that such women suffer a turbulent spiral of often contradictory emotions and, if insufficiently acknowledged at the time of the abortion by self or other, this emotional turmoil can become pushed down and disenfranchised. This paper discusses the nature of this entrapped grief by reviewing the literature and reporting on some phenomenological case study research. A final section discusses integrative psychotherapy approaches to working in this area. Better understanding of the experience of traumatic abortion may enable therapists to be more present to this phenomenon, in particular the voicelessness some clients may experience, rendering them unable to process their feelings about the event and associated loss.

  11. Entrapment of dye molecules within submicron silver particles

    Energy Technology Data Exchange (ETDEWEB)

    Yosef, Itzik; Avnir, David, E-mail: david@chem.ch.huji.ac.il [Hebrew University of Jerusalem, Institute of Chemistry (Israel)

    2011-09-15

    We describe a method for the preparation of metal-organic composites submicron particles. Specifically, the preparation of silver particle-clusters 150-200 nm in size, doped with an organic dye Congo-red, is reported. The use of sodium citrate coupled with sodium hypophosphite facilitated the formation of these particle-clusters, which were fully characterized by TEM analysis, Zeta potential and size measurements, scanning electron microscopy, UV-Vis measurements, and thermogravimetric analysis. The latter reveals a catalytic action of the metal on the thermal oxidative decomposition of the entrapped dye. The use of these particles to obtain dense thin metallic films was demonstrated by the coating of ITO glass.

  12. Entrapment of platelets in the penis during and after erection

    International Nuclear Information System (INIS)

    Bornman, M.S.; Du Plessis, D.J.; Dormehl, I.C.; Du Plessis, M.; Jacobs, D.J.; Maree, M.

    1986-01-01

    Because of the development of hypercoagulability and the deposition of fibrin in the penis during erection a study of the possible role of platelets in this process was undertaken. Platelets response was studied in 9 adult chacma baboons (Papio ursinus) using autologous in vitro indium-111-labelled platelets and sequential scintigraphy of the penis during erection. The blood pooling pattern was obtained using in vivo technetium-99m-labelled red cells in a similar investigation. A statistically significant retention of platelets occured during and after erection, wich could not be attributed to blood pooling (P < 0,05). Entrapment of platelets could lead to enhanced activation, and might play a significant role in hypercoagulability and fibrin deposition during erection. Therefore platelets could be an important factor in the pathogenesis of ageing impotence

  13. Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome.

    Science.gov (United States)

    Burkhart, Keith K; Abernethy, Darrell; Jackson, David

    2015-06-01

    Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was also analyzed for an internal comparison of the drugs most highly associated with SJS. Cyclooxygenases 1 and 2, carbonic anhydrase 2, and sodium channel 2 alpha were identified as disproportionately associated with SJS. Cytochrome P450 (CYPs) 3A4 and 2C9 are disproportionately represented as metabolizing enzymes of the drugs associated with SJS adverse event reports. Multidrug resistance protein 1 (MRP-1), organic anion transporter 1 (OAT1), and PEPT2 were also identified and are highly associated with the transport of these drugs. A detailed review of the molecular targets identifies important roles for these targets in immune response. The association with CYP metabolizing enzymes suggests that reactive metabolites and oxidative stress may have a contributory role. Drug transporters may enhance intracellular tissue concentrations and also have vital physiologic roles that impact keratinocyte proliferation and survival. Data mining FAERS may be used to hypothesize mechanisms for adverse drug events by identifying molecular targets that are highly associated with drug-induced adverse events. The information gained may contribute to systems biology disease models.

  14. Effect of Drug Loading Method and Drug Physicochemical Properties on the Material and Drug Release Properties of Poly (Ethylene Oxide Hydrogels for Transdermal Delivery

    Directory of Open Access Journals (Sweden)

    Rachel Shet Hui Wong

    2017-07-01

    Full Text Available Novel poly (ethylene oxide (PEO hydrogel films were synthesized via UV cross-linking with pentaerythritol tetra-acrylate (PETRA as cross-linking agent. The purpose of this work was to develop a novel hydrogel film suitable for passive transdermal drug delivery via skin application. Hydrogels were loaded with model drugs (lidocaine hydrochloride (LID, diclofenac sodium (DIC and ibuprofen (IBU via post-loading and in situ loading methods. The effect of loading method and drug physicochemical properties on the material and drug release properties of medicated film samples were characterized using scanning electron microscopy (SEM, swelling studies, differential scanning calorimetry (DSC, fourier transform infrared spectroscopy (FT-IR, tensile testing, rheometry, and drug release studies. In situ loaded films showed better drug entrapment within the hydrogel network and also better polymer crystallinity. High drug release was observed from all studied formulations. In situ loaded LID had a plasticizing effect on PEO hydrogel, and films showed excellent mechanical properties and prolonged drug release. The drug release mechanism for the majority of medicated PEO hydrogel formulations was determined as both drug diffusion and polymer chain relaxation, which is highly desirable for controlled release formulations.

  15. Results of conservative, surgical treatment and rehabilitation of entrapment neuropathies in elderly patients in geriatric practice

    Directory of Open Access Journals (Sweden)

    Jadwiga Główczewska

    2017-03-01

    Full Text Available Entrapment neuropahies of upper limbs can cause mainly nocturnal neuropathic pain and impaired manual dexterity. The most common entrapment neuropathy is carpal tunnel syndrome and ulnar groove syndrome - ulnar nerve entrapment at the elbow. Treatment of entrapment neuropathies is both analgetic therapy and physiotherapy. In the cases of conservative treatment inefficiencies surgical decompression of nerves is performed. Authors of this oublication present results of both conservative  and surgical of entrapment neuropathies in patients over 65 years old. Among the 17 patients with entraoment neuropathies 12 of them underwent surgical treatment. Achieved partial improvement in pain, mostly nocturnal and improving the quality of life and dexterity. In comparison, however, a group of younger patients who underwent surgery for the improvement was less spectacular, which may testify advancement and irreversibility of changes in older patients.

  16. Tantalum surface oxidation: Bond relaxation, energy entrapment, and electron polarization

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Yongling [Key Laboratory of Low-Dimensional Materials and Application Technologies (Ministry of Education), Hunan Provincial Key Laboratory of Thin Film Materials and Devices, Faculty of Materials Science and Engineering, Xiangtan University, Hunan 411105 (China); Bo, Maolin [Yangtze Normal University, College of Mechanical and Electrical Engineering, Chongqing 408100 (China); Wang, Yan [School of Information and Electronic Engineering, Hunan University of Science and Technology, Hunan 411201 (China); Liu, Yonghui [Key Laboratory of Low-Dimensional Materials and Application Technologies (Ministry of Education), Hunan Provincial Key Laboratory of Thin Film Materials and Devices, Faculty of Materials Science and Engineering, Xiangtan University, Hunan 411105 (China); Sun, Chang Q. [NOVITAS, School of Electrical and Electronic Engineering, Nanyang Technological University, Singapore 639798 (Singapore); Huang, Yongli, E-mail: huangyongli@xtu.edu.cn [Key Laboratory of Low-Dimensional Materials and Application Technologies (Ministry of Education), Hunan Provincial Key Laboratory of Thin Film Materials and Devices, Faculty of Materials Science and Engineering, Xiangtan University, Hunan 411105 (China)

    2017-02-28

    Graphical abstract: The bond, electron and energy relaxation result in core level energy shift, local densification, quantum entrapment and electron polarization of bonding electrons. - Highlights: • Increasing the oxygen coverage lowers the adsorption energy associated with lattice reconstruction. • Electrons transfer from Ta surface atoms to sp-hydrated oxygen, creating dipole moment that decreases the work function. • Oxygen chemisorption modified valence density-of-state (DOS) for Ta with four excessive DOS features: O−Ta bonding, O{sup 2−} lone pairs, Ta+ electron holes, and the lone-pair polarized Ta dipoles. • The bond, electron and energy relaxation between surface undercoordinated atoms are responsible for core level energy shift, local densification, quantum entrapment and electron polarization of bonding electrons. - Abstract: A combination of photoelectron spectrometric analysis and density functional theory calculations has enabled reconciliation of the bond-energy-electron relaxation for the Ta(100, 110, 111) surfaces chemisorbed with oxygen at different coverages. Results show that increasing oxygen coverage lowers the adsorption energy associated with lattice reconstruction. Valence electrons transfer from Ta surface atoms to oxygen to create four excessive DOS features in terms of O−Ta bonding, lone pairs of oxygen, Ta{sup +} electron holes, and polarized Ta dipoles. Oxidation proceeds in the following dynamics: oxygen gets electrons from two neighboring Ta atoms left behind Ta{sup +}; the sp{sup 3}-orbital hybridization takes place with additional two electron lone pairs, the lone pairs polarize the other two Ta neighbors becoming dipoles. X-ray photoelectron spectral analysis results in the 4f binding energy of an isolated Ta atom and its shift upon bond formation and oxidation. Exercises provide not only a promising numerical approach for the quantitative information about the bond and electronic behavior but also consistent

  17. Tantalum surface oxidation: Bond relaxation, energy entrapment, and electron polarization

    International Nuclear Information System (INIS)

    Guo, Yongling; Bo, Maolin; Wang, Yan; Liu, Yonghui; Sun, Chang Q.; Huang, Yongli

    2017-01-01

    Graphical abstract: The bond, electron and energy relaxation result in core level energy shift, local densification, quantum entrapment and electron polarization of bonding electrons. - Highlights: • Increasing the oxygen coverage lowers the adsorption energy associated with lattice reconstruction. • Electrons transfer from Ta surface atoms to sp-hydrated oxygen, creating dipole moment that decreases the work function. • Oxygen chemisorption modified valence density-of-state (DOS) for Ta with four excessive DOS features: O−Ta bonding, O"2"− lone pairs, Ta+ electron holes, and the lone-pair polarized Ta dipoles. • The bond, electron and energy relaxation between surface undercoordinated atoms are responsible for core level energy shift, local densification, quantum entrapment and electron polarization of bonding electrons. - Abstract: A combination of photoelectron spectrometric analysis and density functional theory calculations has enabled reconciliation of the bond-energy-electron relaxation for the Ta(100, 110, 111) surfaces chemisorbed with oxygen at different coverages. Results show that increasing oxygen coverage lowers the adsorption energy associated with lattice reconstruction. Valence electrons transfer from Ta surface atoms to oxygen to create four excessive DOS features in terms of O−Ta bonding, lone pairs of oxygen, Ta"+ electron holes, and polarized Ta dipoles. Oxidation proceeds in the following dynamics: oxygen gets electrons from two neighboring Ta atoms left behind Ta"+; the sp"3-orbital hybridization takes place with additional two electron lone pairs, the lone pairs polarize the other two Ta neighbors becoming dipoles. X-ray photoelectron spectral analysis results in the 4f binding energy of an isolated Ta atom and its shift upon bond formation and oxidation. Exercises provide not only a promising numerical approach for the quantitative information about the bond and electronic behavior but also consistent insight into the

  18. New approach for high-throughput screening of drug activity on Plasmodium liver stages.

    NARCIS (Netherlands)

    Gego, A.; Silvie, O.; Franetich, J.F.; Farhati, K.; Hannoun, L.; Luty, A.J.F.; Sauerwein, R.W.; Boucheix, C.; Rubinstein, E.; Mazier, D.

    2006-01-01

    Plasmodium liver stages represent potential targets for antimalarial prophylactic drugs. Nevertheless, there is a lack of molecules active on these stages. We have now developed a new approach for the high-throughput screening of drug activity on Plasmodium liver stages in vitro, based on an

  19. An Evaluation of Immediate Outcomes and Fidelity of a Drug Abuse Prevention Program in Continuation High Schools: Project towards No Drug Abuse (TND)

    Science.gov (United States)

    Lisha, Nadra E.; Sun, Ping; Rohrbach, Louise A.; Spruijt-Metz, Donna; Unger, Jennifer B.; Sussman, Steve

    2012-01-01

    The present study provides an implementation fidelity, process, and immediate outcomes evaluation of Project Towards No Drug Abuse (TND), a drug prevention program targeting continuation high school youth (n = 1426) at risk for drug abuse. A total of 24 schools participated in three randomized conditions: TND Only, TND and motivational…

  20. Highly water-soluble, porous, and biocompatible boron nitrides for anticancer drug delivery.

    Science.gov (United States)

    Weng, Qunhong; Wang, Binju; Wang, Xuebin; Hanagata, Nobutaka; Li, Xia; Liu, Dequan; Wang, Xi; Jiang, Xiangfen; Bando, Yoshio; Golberg, Dmitri

    2014-06-24

    Developing materials for "Nano-vehicles" with clinically approved drugs encapsulated is envisaged to enhance drug therapeutic effects and reduce the adverse effects. However, design and preparation of the biomaterials that are porous, nontoxic, soluble, and stable in physiological solutions and could be easily functionalized for effective drug deliveries are still challenging. Here, we report an original and simple thermal substitution method to fabricate perfectly water-soluble and porous boron nitride (BN) materials featuring unprecedentedly high hydroxylation degrees. These hydroxylated BNs are biocompatible and can effectively load anticancer drugs (e.g., doxorubicin, DOX) up to contents three times exceeding their own weight. The same or even fewer drugs that are loaded on such BN carriers exhibit much higher potency for reducing the viability of LNCaP cancer cells than free drugs.

  1. Elucidation of release characteristics of highly soluble drug trimetazidine hydrochloride from chitosan-carrageenan matrix tablets.

    Science.gov (United States)

    Li, Liang; Wang, Linlin; Shao, Yang; Tian, Ye; Li, Conghao; Li, Ying; Mao, Shirui

    2013-08-01

    The aim of this study was to better understand the underlying drug release characteristics from matrix tablets based on the combination of chitosan (CS) and different types of carrageenans [kappa (κ)-CG, iota (ι)-CG, and lambda (λ)-CG]. Highly soluble trimetazidine hydrochloride (TH) was used as a model drug. First, characteristics of drug release from different formulations were investigated, and then in situ complexation capacity of CG with TH and CS was studied by differential scanning calorimetry and Fourier transform infrared spectroscopy. Erosion and swelling of matrix were also characterized to better understand the drug-release mechanisms. Effects of pH and ionic strength on drug release were also studied. It was found that not only ι-CG and λ-CG could reduce the burst release of TH by the effect of TH-CG interaction, CS-ι-CG- and CS-λ-CG-based polyelectrolyte film could further modify the controlled-release behavior, but not CS-κ-CG. High pH and high ionic strength resulted in faster drug release from CS-κ-CG- and CS-ι-CG-based matrix, but drug release from CS-λ-CG-based matrix was less sensitive to pH and ionic strength. In conclusion, CS-λ-CG-based matrix tablets are quite promising as controlled-release drug carrier based on multiple mechanisms. Copyright © 2013 Wiley Periodicals, Inc.

  2. Treating tuberculosis with high doses of anti-TB drugs: mechanisms and outcomes.

    Science.gov (United States)

    Xu, Yuhui; Wu, Jianan; Liao, Sha; Sun, Zhaogang

    2017-10-03

    Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.

  3. Single molecule studies of solvent-dependent diffusion and entrapment in poly(dimethylsiloxane) thin films.

    Science.gov (United States)

    Lange, Jeffrey J; Culbertson, Christopher T; Higgins, Daniel A

    2008-12-15

    Single molecule microscopic and spectroscopic methods are employed to probe the mobility and physical entrapment of dye molecules in dry and solvent-loaded poly(dimethylsiloxane) (PDMS) films. PDMS films of approximately 220 nm thickness are prepared by spin casting dilute solutions of Sylgard 184 onto glass coverslips, followed by low temperature curing. A perylene diimide dye (BPPDI) is used to probe diffusion and molecule-matrix interactions. Two classes of dye-loaded samples are investigated: (i) those incorporating dye dispersed throughout the films ("in film" samples) and (ii) those in which the dye is restricted primarily to the PDMS surface ("on film" samples). Experiments are performed under dry nitrogen and at various levels of isopropyl alcohol (IPA) loading from the vapor phase. A PDMS-coated quartz-crystal microbalance is employed to monitor solvent loading and drying of the PDMS and to ensure equilibrium conditions are achieved. Single molecules are shown to be predominantly immobile under dry conditions and mostly mobile under IPA-saturated conditions. Quantitative methods for counting the fluorescent spots produced by immobile single molecules in optical images of the samples demonstrate that the population of mobile molecules increases nonlinearly with IPA loading. Even under IPA saturated conditions, the population of fixed molecules is found to be greater than zero and is greatest for "in film" samples. Fluorescence correlation spectroscopy is used to measure the apparent diffusion coefficient for the mobile molecules, yielding a mean value of D = 1.4(+/-0.4) x 10(-8) cm(2)/s that is virtually independent of IPA loading and sample class. It is concluded that a nonzero population of dye molecules is physically entrapped within the PDMS matrix under all conditions. The increase in the population of mobile molecules under high IPA conditions is attributed to the filling of film micropores with solvent, rather than by incorporation of molecularly

  4. Highly lipophilic pluronics-conjugated polyamidoamine dendrimer nanocarriers as potential delivery system for hydrophobic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Thi Tram Chau [Institute of Research and Development, Duy Tan University, Da Nang City 550000 (Viet Nam); Department of Chemical Engineering, Industrial University of HCMC, HCMC 70000 (Viet Nam); Nguyen, Cuu Khoa, E-mail: nckhoavnn@yahoo.com [Department of Materials and Pharmaceutical Chemistry, Vietnam Academy of Science and Technology, HCMC 70000 (Viet Nam); Nguyen, Thi Hiep [Biomedical Engineering Department, International University, National Universities in HCMC, HCMC 70000 (Viet Nam); Tran, Ngoc Quyen, E-mail: tnquyen@iams.vast.vn [Institute of Research and Development, Duy Tan University, Da Nang City 550000 (Viet Nam); Department of Materials and Pharmaceutical Chemistry, Vietnam Academy of Science and Technology, HCMC 70000 (Viet Nam)

    2017-01-01

    In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, {sup 1}H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15–377.14 kDa and around 60–180 nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4.0-P123) exhibiting a higher drug loading efficiency (up to 76.25%) in comparison with another pluronics. Live/dead fibroblast cell staining assay mentioned that all conjugated nanocarriers are highly biocompatible. The drug-loaded nanocarriers also indicated a highly anti-proliferative activity against MCF-7 breast cancer cell. The obtained results demonstrated a great potential of the highly lipophilic pluronics-conjugated nanocarriers in hydrophobic drugs delivery for biomedical applications. - Highlights: • Biocompatible pluronic-conjugated polyamidoamine dendrimers were prepared at nanoscale for drug delivery. • The dendrimer nanocarrier was decorated with a lipophilic pluronic exhibiting a higher drug loading efficiency. • The pluronic-functionalized nanocarriers demonstrated a great potential for delivering hydrophobic drugs.

  5. Current position of high-resolution MS for drug quantification in clinical & forensic toxicology.

    Science.gov (United States)

    Meyer, Markus R; Helfer, Andreas G; Maurer, Hans H

    2014-08-01

    This paper reviews high-resolution MS approaches published from January 2011 until March 2014 for the quantification of drugs (of abuse) and/or their metabolites in biosamples using LC-MS with time-of-flight or Orbitrap™ mass analyzers. Corresponding approaches are discussed including sample preparation and mass spectral settings. The advantages and limitations of high-resolution MS for drug quantification, as well as the demand for a certain resolution or a specific mass accuracy are also explored.

  6. Light-Addressed Electrodeposition of Enzyme-Entrapped Chitosan Membranes for Multiplexed Enzyme-Based Bioassays Using a Digital Micromirror Device

    Directory of Open Access Journals (Sweden)

    Yeu-Long Jiang

    2013-08-01

    Full Text Available This paper describes a light-addressed electrolytic system used to perform an electrodeposition of enzyme-entrapped chitosan membranes for multiplexed enzyme-based bioassays using a digital micromirror device (DMD. In this system, a patterned light illumination is projected onto a photoconductive substrate serving as a photo-cathode to electrolytically produce hydroxide ions, which leads to an increased pH gradient. The high pH generated at the cathode can cause a local gelation of chitosan through sol-gel transition. By controlling the illumination pattern on the DMD, a light-addressed electrodeposition of chitosan membranes with different shapes and sizes, as well as multiplexed micropatterning, was performed. The effect of the illumination time of the light pattern on the dimensional resolution of chitosan membrane formation was examined experimentally. Moreover, multiplexed enzyme-based bioassay of enzyme-entrapped chitosan membranes was also successfully demonstrated through the electrodeposition of the chitosan membranes with various shapes/sizes and entrapping different enzymes. As a model experiment, glucose and ethanol were simultaneously detected in a single detection chamber without cross-talk using shape-coded chitosan membranes entrapped with glucose oxidase (GOX, peroxidase (POD, and Amplex Red (AmR or alcohol oxidase (AOX, POD, and AmR by using same fluorescence indicator (AmR.

  7. Application of drug delivery system for boron neutron capture therapy. Basic research toward clinical application

    International Nuclear Information System (INIS)

    Yanagie, Hironobu; Takahashi, Hiroyuki

    2010-01-01

    Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between 10 B and thermal neutrons ( 10 B+ 1 n → 7 Li+ 4 He (α) +2.31 MeV (93.7%)/2.79 MeV (6.3%)). The resulting lithium ions and αparticles are high linear energy transfer (LET) particles which give high biological effect. Their short range in tissue (5-9 μm) restricts radiation damage to those cells in which boron atoms are located at the time of neutron irradiation. BNCT has been applied clinically for the treatment of malignant brain tumors, malignant melanoma, head and neck cancer and hepatoma etc, recently. Sodium borocaptate (Na 2 10 B 12 H 11 SH; BSH) and borono-phenylalanine ( 10 BPA) are currently being used in clinical treatments. To achieve the selective delivery of boron atoms to cancer cells, drug delivery system (DDS) becomes an attractive intelligent technology as targeting and controlled release of drugs. We have firstly reported that 10 B atoms delivered by immunoliposomes are cytotoxic to human pancreatic carcinoma cells (AsPC-1) after thermal neutron irradiation in vitro. The intra-tumoural injection of boronated immunoliposomes can increase the retention of 10 B atoms in tumour cells, causing suppression of tumour growth in vivo following thermal neutron irradiation. We prepared polyethylene-glycol binding liposomes (PEG-liposomes) as an effective 10 B carrier to obviate phagocytosis by reticuloendotherial systems. We had prepared 10 BSH entrapped Water-in-Oil-in-Water (WOW) emulsion. The 10 B concentration in VX-2 tumour after intra-arterial injection of 10 BSH entrapped WOW emulsion was superior to the groups of 10 BSH entrapped conventional Lipiodol mix emulsion. 10 Boron entrapped WOW emulsion is one of the most useful for intra-arterial boron delivery carrier on BNCT to hepatocellular carcinoma. (author)

  8. The infertility trap: how defeat and entrapment affect depressive symptoms.

    Science.gov (United States)

    Galhardo, A; Moura-Ramos, M; Cunha, M; Pinto-Gouveia, J

    2016-02-01

    Does the perception of failure without a solution or way forward of infertile couples have a mediator role between the importance couples attribute to parenthood and depressive symptoms? The perception of failure without a solution or way forward, assessed by feelings of entrapment and defeat, mediates the effect of the importance of parenthood on depressive symptoms of infertile men and women. Research has documented that the heightened importance of parenthood affects infertile couples' adjustment to infertility and medical treatments. However, it remains unclear which psychological mechanisms and perceptions may underlie the association between having parenthood as a nuclear aspect of life and presenting depressive symptoms related to difficulties in accomplishing that important life goal. Although these links have been scantly addressed in infertility, previous studies have pointed to the role that perceptions of defeat and entrapment have in several psychopathological conditions. The study was cross-sectional. Couples pursuing medical treatment for their fertility problems were invited to participate by their doctors in several public and private clinics. Data collection took place between July 2009 and 2011. One hundred forty-seven infertile couples consented to participate in the study. Both couple members (147 women and 147 men) completed a set of self-report instruments for the assessment of depressive symptoms, perceptions of defeat and entrapment, importance of parenthood and rejection of a childfree lifestyle. Analyses were conducted through Structural Equation Modeling and followed a dyadic analysis strategy, allowing for controlling the interdependence of the data. The hypothesized tested model showed a very good fit to the data [(χ(2) = 68.45, P = 0.014, comparative fit index = 0.98, standardized root-mean-square residual = 0.06 and root mean square error of approximation = 0.06] and explained 67 and 58% of the variability in depressive symptoms in

  9. Applying Fear Appeals Theory for Preventing Drug Abuse among Male High School Students in Tehran

    Directory of Open Access Journals (Sweden)

    K. Witte

    2006-10-01

    Full Text Available Introduction & Objective: Drug abuse is one of the complicated phenomenons in the human communities that it produces health problems. The effect of applying fear appeal message on attitudes and intention against drug abuse, drug resistance skills, knowledge about side effect of drugs and drug abuse related behaviors among male high school students was studied based on applying extended parallel process model as a theoretical framework. Materials & Methods: Two high schools were chosen from six state high schools as an intervention (n=86 and control (n=97 groups. Educational curriculum, that was designed, based on students’ educational needs, appealed students’ fear and recommended messages developed students' ability for resisting against drugs. Before intervention 5-6 students who were known as a favourite and leader of students, were selected by student’s opinion in each class as students' leaders. The each leader of the group had a coordinator and mediate role between his group and health educators. Henceforth a favourite teacher was chosen by students’ vote for helping health educators and participated in the educational intervention program.Results: The result showed that educational manipulation had significant effect on intervention group’s average response for intention (t= -4.03, p<0.000 and attitude against drug abuse (t= -6.19, p<0.000, peer resistance skills (t=-0.82, p<0.000, and knowledge (t= -10.88, p<0.000. In addition, it was not found positive urinary rapid immune-chromatography test for opium and marijuana in the intervention group whereas 6.3% in the control groups.Conclusion: This findings suggest that applying fear appeals theories and effective health risk message would be an efficient tool for preventing drug abuse education programs but further studies are needed to define function of EPPM as a effective model for creating social inoculation against drug abuse among non- drug expose adolescents.

  10. Fish entrapment of the seawater intake of a power plant at Karachi coast

    International Nuclear Information System (INIS)

    Moazzam, M.; Niaz Risvi, S.H.

    1980-01-01

    The study deals with the entrapment of fishes in the intake of Karachi Nuclear Power Plant. A total of 62 species of marine fishes belonging to 43 genera were observed entrapped in the seawater intake. Therapon puta, Liza waigiensis, Abudefduf septemfasciatus, and Lagoceptalus inermis were the most common. Mass mortalities of the juveniles of Sardinella sindensis were recorded in September and October of 1974, 1975, and 1977. Commercially important fishes such as sardines, mullets and anchovies, were entrapped in the intake of the power plant in considerable numbers at various times of the year. The majority of fishes removed from the screen washes of the power plants were killed by impingement. (Auth.)

  11. Sorption of chrysoidine by row cork and cork entrapped in calcium alginate beads

    Directory of Open Access Journals (Sweden)

    Valeria M. Nurchi

    2014-01-01

    The influence on the sorption of pH, initial dye concentration, and particle size, as well as the efficiency of the entrapment, have been investigated. The maximum sorption was found for cork samples of fine particle size (FC, in both row and entrapped forms, at pH 7; conversely, at pH 4 the difference is significant (0.12 mmol/g for row cork and 0.20 mmol/g for entrapped cork, evoking a cooperation of alginate in binding the positively charged chrysoidine molecule.

  12. High-Throughput Screening Using Mass Spectrometry within Drug Discovery.

    Science.gov (United States)

    Rohman, Mattias; Wingfield, Jonathan

    2016-01-01

    In order to detect a biochemical analyte with a mass spectrometer (MS) it is necessary to ionize the analyte of interest. The analyte can be ionized by a number of different mechanisms, however, one common method is electrospray ionization (ESI). Droplets of analyte are sprayed through a highly charged field, the droplets pick up charge, and this is transferred to the analyte. High levels of salt in the assay buffer will potentially steal charge from the analyte and suppress the MS signal. In order to avoid this suppression of signal, salt is often removed from the sample prior to injection into the MS. Traditional ESI MS relies on liquid chromatography (LC) to remove the salt and reduce matrix effects, however, this is a lengthy process. Here we describe the use of RapidFire™ coupled to a triple-quadrupole MS for high-throughput screening. This system uses solid-phase extraction to de-salt samples prior to injection, reducing processing time such that a sample is injected into the MS ~every 10 s.

  13. Dendrimers for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Abhay Singh Chauhan

    2018-04-01

    Full Text Available Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine (PAMAM dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i formulation and (ii nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

  14. ENTRAPMENT OF FLUORESCENT E. COLI CELLS IN ALGINATE GEL

    Directory of Open Access Journals (Sweden)

    T. VINTILA

    2009-05-01

    Full Text Available By this experiment we will demonstrate the possibility to obtain genetically modified microbial strains that can be used as markers in different studies. The trait transferred in this study is the fluorescence in UV light expressed by a gene isolated from jellyfish. This gene was insered into a plasmid carrying ampiciline resistance and in the operon for arabinose fermentation. The plasmid was called pGLO. E coli HB101 K-12, ampicillin resistant colonies has been obtained. The colonies on the LB/amp/ara plate fluoresce green under UV light and the transformed colonies can grow on ampicillin. Transformation efficiency = 362 transformed colonies/ μg DNA. The cells where immobilized by entrapment in alginate gel to study the phenomenon involved in cells immobilization. After immobilization in alginate gel, 5x104 cells of E. coli pGLO / capsule and 1,4 x 105 cells of E. coli HB101/capsule has been found. Fluorescent microscopy revealed the presence of pGLO carrying cells into the capsules. After cultivation of alginate capsules containing E. coli in LB broth, and fluorescent microscopy of the capsule sections, several observations of the phenomenon involved in continuous fermentation using biocatalysts in has been made. These cells grow and migrate to the cortical part of the matrix where they are immobilized.

  15. A BOD monitoring disposable reactor with alginate-entrapped bacteria.

    Science.gov (United States)

    Villalobos, Patricio; Acevedo, Cristian A; Albornoz, Fernando; Sánchez, Elizabeth; Valdés, Erika; Galindo, Raúl; Young, Manuel E

    2010-10-01

    Biochemical oxygen demand (BOD) is a measure of the amount of dissolved oxygen that is required for the biochemical oxidation of the organic compounds in 5 days. New biosensor-based methods have been conducted for a faster determination of BOD. In this study, a mathematical model to evaluate the feasibility of using a BOD sensor, based on disposable alginate-entrapped bacteria, for monitoring BOD in situ was applied. The model considers the influences of alginate bead size and bacterial concentration. The disposable biosensor can be adapted according to specific requirements depending on the organic load contained in the wastewater. Using Klein and Washausen parameter in a Lineweaver-Burk plot, the glucose diffusivity was calculated in 6.4 × 10(-10) (m2/s) for beads of 1 mm in diameter and slight diffusion restrictions were observed (n = 0.85). Experimental results showed a correlation (p < 0.05) between the respirometric peak and the standard BOD test. The biosensor response was representative of BOD.

  16. Uranium biosorption by Trichoderma harzianum entrapped in polyester foam beads

    International Nuclear Information System (INIS)

    Khalid, A.M.; Shemsi, A.M.; Akhtar, K.; Anwar, M.A.

    1993-01-01

    Mechanism of uranium biosorption by resting cells of Trichoderma harzianum was studied at pH 4.5. Time-dependent uptake of uranium by Trichoderma harzianum was also determined. Various cations (Na, K, Ca and Fe, etc.) were found to affect the adsorption capability of these cells. Different theoretical thermodynamic models governing the adsorption behavior of uranium were also tested and it was found to follow the Langmuir and Freundlich adsorption isotherms. The constants of Freundlich adsorption isotherm A and 1/n were found to be 1.5 x 10 -6 mole/g and 0.31 respectively. Dubinin Radushkevich equation was tested and the maximum adsorption capacity (X m ) of Trichoderma harzianum and sorption energy (E s ) for the ion exchange process computed. Data of uranium sorption were also examined using Weber Morris's equation. The upscaling of uranium biosorption by Trichoderma harzianum entrapped in commercial foam (polyesters) was carried out in glass columns. It was found to recover more than 85% of the total uranium present in bacterial leachate

  17. Intracellular fate of Ureaplasma parvum entrapped by host cellular autophagy.

    Science.gov (United States)

    Nishiumi, Fumiko; Ogawa, Michinaga; Nakura, Yukiko; Hamada, Yusuke; Nakayama, Masahiro; Mitobe, Jiro; Hiraide, Atsushi; Sakai, Norio; Takeuchi, Makoto; Yoshimori, Tamotsu; Yanagihara, Itaru

    2017-06-01

    Genital mycoplasmas, including Ureaplasma spp., are among the smallest human pathogenic bacteria and are associated with preterm birth. Electron microscopic observation of U. parvum showed that these prokaryotes have a regular, spherical shape with a mean diameter of 146 nm. U. parvum was internalized into HeLa cells by clathrin-mediated endocytosis and survived for at least 14 days around the perinuclear region. Intracellular U. parvum reached endosomes in HeLa cells labeled with EEA1, Rab7, and LAMP-1 within 1 to 3 hr. After 3 hr of infection, U. parvum induced the cytosolic accumulation of galectin-3 and was subsequently entrapped by the autophagy marker LC3. However, when using atg7 -/- MEF cells, autophagy was inadequate for the complete elimination of U. parvum in HeLa cells. U. parvum also colocalized with the recycling endosome marker Rab11. Furthermore, the exosomes purified from infected HeLa cell culture medium included U. parvum. In these purified exosomes ureaplasma lipoprotein multiple banded antigen, host cellular annexin A2, CD9, and CD63 were detected. This research has successfully shown that Ureaplasma spp. utilize the host cellular membrane compartments possibly to evade the host immune system. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  18. [High prevalence of drug consumption and sexual risk behaviors in men who have sex with men].

    Science.gov (United States)

    Folch, Cinta; Fernández-Dávila, Percy; Ferrer, Laia; Soriano, Raúl; Díez, Mercedes; Casabona, Jordi

    2015-08-07

    To describe the pattern of drug use among men who have sex with men (MSM) living in Spain and its association with sexual risk practices. The European MSM Internet Survey was implemented in 2010 in 38 European countries on websites for MSM and collected data on sociodemographics, sexual behavior, and other sexual health variables. The association between unprotected anal intercourse (UAI) with casual partners and drug consumption was evaluated using multivariate logistic regression models. Among the 13,111 participants, most consumed drugs were cannabis (30.1%), popper (28.4%) and cocaine (18.7%). The risk of UAI with casual partners was 1.5 among those who had used drugs in relation to the other participants. The proportion of MSM who had injected drugs at least once in life was 2.5%, and 1.4% in the last 12 months. The prevalence of UAI with casual partners (53.4%), human immunodeficiency virus (HIV) (23%), hepatitis C (8.2%) and sexually transmitted infections (STI) (15.8%) was higher in MSM injectors related to those who had not used injected drugs (P<.05). The results of this study confirm a high prevalence of drug use in MSM and their relationship to sexual risk behavior. Although the use of injected drugs in MSM is a minority, this group reported a higher level of sexual risk behaviors, self-reported HIV, hepatitis C and other STI. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  19. Relationship between Drugs Use and Sexual Risk Behaviors among Senior High School Students

    Directory of Open Access Journals (Sweden)

    Yola Yuniaarti Herijanto

    2017-03-01

    Full Text Available Background: Drugs use and risky sexual behavior among teenager are some of crucial problems arising in Indonesia. Statistic showed that there is an increasing prevalence in drugs use and risky sexual behavior among teenagers. This study was conducted to analyze the relationship between drugs use and risky sexual behaviors among high school students. Methods: An analytic study involving 432 students in 5 state high schools located in Kerees region Bandung, West Java, Indonesia, was carried out in 2013. The region was chosen due the high prevalence of substance abuse. The inclusion criteria were every high school students in the Karees region. The exclusion criteria were the students who refused to participate in the study, did not come when the sample was taken, and did not fill the questionnaire completely. The instruments used for the study were questionnaires with cross-sectional technique. Furthermore, the questionnaire used for analyzing drugs use was Addiction Severity Index-Lite Version (ASI-lite questionnaire; with additional questionnaire to analyze risky sexual behaviors. Results: Out of 432 students, 23.8% students already engaged to one or more risky sexual behavior. Among all respondents, the prevalence of students who had already done kissing was 22.7%, necking 9.3%, petting 7.2% and sexual intercourse 1.2%. Illegal drugs had been used at least once by 21.8% students. According to Chi-square test, drugs use and risky sexual behavior were related. Conclusions:The prevalence of both drugs use and risky sexual behaviors are high and students who use drugs are more prone to do risky sexual behavior.

  20. Lysosomes as mediators of drug resistance in cancer.

    Science.gov (United States)

    Zhitomirsky, Benny; Assaraf, Yehuda G

    2016-01-01

    Drug resistance remains a leading cause of chemotherapeutic treatment failure and cancer-related mortality. While some mechanisms of anticancer drug resistance have been well characterized, multiple mechanisms remain elusive. In this respect, passive ion trapping-based lysosomal sequestration of multiple hydrophobic weak-base chemotherapeutic agents was found to reduce the accessibility of these drugs to their target sites, resulting in a markedly reduced cytotoxic effect and drug resistance. Recently we have demonstrated that lysosomal sequestration of hydrophobic weak base drugs triggers TFEB-mediated lysosomal biogenesis resulting in an enlarged lysosomal compartment, capable of enhanced drug sequestration. This study further showed that cancer cells with an increased number of drug-accumulating lysosomes are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. In addition to passive drug sequestration of hydrophobic weak base chemotherapeutics, other mechanisms of lysosome-mediated drug resistance have also been reported; these include active lysosomal drug sequestration mediated by ATP-driven transporters from the ABC superfamily, and a role for lysosomal copper transporters in cancer resistance to platinum-based chemotherapeutics. Furthermore, lysosomal exocytosis was suggested as a mechanism to facilitate the clearance of chemotherapeutics which highly accumulated in lysosomes, thus providing an additional line of resistance, supplementing the organelle entrapment of chemotherapeutics away from their target sites. Along with these mechanisms of lysosome-mediated drug resistance, several approaches were recently developed for the overcoming of drug resistance or exploiting lysosomal drug sequestration, including lysosomal photodestruction and drug-induced lysosomal membrane permeabilization. In this review we explore the current literature addressing the role of lysosomes in mediating cancer drug

  1. Mechanisms of Evolution in High-Consequence Drug Resistance Plasmids

    Directory of Open Access Journals (Sweden)

    Susu He

    2016-12-01

    Full Text Available The dissemination of resistance among bacteria has been facilitated by the fact that resistance genes are usually located on a diverse and evolving set of transmissible plasmids. However, the mechanisms generating diversity and enabling adaptation within highly successful resistance plasmids have remained obscure, despite their profound clinical significance. To understand these mechanisms, we have performed a detailed analysis of the mobilome (the entire mobile genetic element content of a set of previously sequenced carbapenemase-producing Enterobacteriaceae (CPE from the National Institutes of Health Clinical Center. This analysis revealed that plasmid reorganizations occurring in the natural context of colonization of human hosts were overwhelmingly driven by genetic rearrangements carried out by replicative transposons working in concert with the process of homologous recombination. A more complete understanding of the molecular mechanisms and evolutionary forces driving rearrangements in resistance plasmids may lead to fundamentally new strategies to address the problem of antibiotic resistance.

  2. High risk behavior for HIV transmission among former injecting drug users:a survey from Indonesia

    Directory of Open Access Journals (Sweden)

    Iskandar Shelly

    2010-08-01

    Full Text Available Abstract Background Injecting drug use is an increasingly important cause of HIV transmission in most countries worldwide, especially in eastern Europe, South America, and east and southeast Asia. Among people actively injecting drugs, provision of clean needles and opioid substitution reduce HIV-transmission. However, former injecting drug users (fIDUs are often overlooked as a high risk group for HIV transmission. We compared HIV risk behavior among current and former injecting drug users (IDUs in Indonesia, which has a rapidly growing HIV-epidemic largely driven by injecting drug use. Methods Current and former IDUs were recruited by respondent driven sampling in an urban setting in Java, and interviewed regarding drug use and HIV risk behavior using the European Addiction Severity Index and the Blood Borne Virus Transmission Questionnaire. Drug use and HIV transmission risk behavior were compared between current IDUs and former IDUs, using the Mann-Whitney and Pearson Chi-square test. Results Ninety-two out of 210 participants (44% were self reported former IDUs. Risk behavior related to sex, tattooing or piercing was common among current as well as former IDUs, 13% of former IDUs were still exposed to contaminated injecting equipment. HIV-infection was high among former (66% and current (60% IDUs. Conclusion Former IDUs may contribute significantly to the HIV-epidemic in Indonesia, and HIV-prevention should therefore also target this group, addressing sexual and other risk behavior.

  3. Primary drug resistance in a region with high burden of tuberculosis. A critical problem

    Directory of Open Access Journals (Sweden)

    Cecilia Villa-Rosas

    2015-03-01

    Full Text Available Objective. To determine rates of drug resistance in new cases of pulmonary tuberculosis in a region with a high burden of the disease. Materials and methods. New case suspects were referred for drug susceptibility testing. Results. 28.9% of new cases were resistant to at least one first line drug; 3.9% had a multidrug-resistant strain, 15.6% a monoresistant strain and 9.4% a polyresistant strain. Conclusion. Our rate of drug resistant tuberculosis in new cases is very high; this has important clinical implications, since even monoresistance can have a negative impact on the outcome of new cases treated empirically with a six month regimen.

  4. 3D extrusion printing of high drug loading immediate release paracetamol tablets.

    Science.gov (United States)

    Khaled, Shaban A; Alexander, Morgan R; Wildman, Ricky D; Wallace, Martin J; Sharpe, Sonja; Yoo, Jae; Roberts, Clive J

    2018-03-01

    The manufacture of immediate release high drug loading paracetamol oral tablets was achieved using an extrusion based 3D printer from a premixed water based paste formulation. The 3D printed tablets demonstrate that a very high drug (paracetamol) loading formulation (80% w/w) can be printed as an acceptable tablet using a method suitable for personalisation and distributed manufacture. Paracetamol is an example of a drug whose physical form can present challenges to traditional powder compression tableting. Printing avoids these issues and facilitates the relatively high drug loading. The 3D printed tablets were evaluated for physical and mechanical properties including weight variation, friability, breaking force, disintegration time, and dimensions and were within acceptable range as defined by the international standards stated in the United States Pharmacopoeia (USP). X-ray Powder Diffraction (XRPD) was used to identify the physical form of the active. Additionally, XRPD, Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC) were used to assess possible drug-excipient interactions. The 3D printed tablets were evaluated for drug release using a USP dissolution testing type I apparatus. The tablets showed a profile characteristic of the immediate release profile as intended based upon the active/excipient ratio used with disintegration in less than 60 s and release of most of the drug within 5 min. The results demonstrate the capability of 3D extrusion based printing to produce acceptable high-drug loading tablets from approved materials that comply with current USP standards. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Improving the performance of electrochemical microsensors based on enzymes entrapped in a redox hydrogel

    International Nuclear Information System (INIS)

    Mitala, J.J.; Michael, A.C.

    2006-01-01

    Microsensors based on carbon fiber microelectrodes coated with enzyme-entrapping redox hydrogels facilitate the in vivo detection of substances of interest within the central nervous system, including hydrogen peroxide, glucose, choline and glutamate. The hydrogel, formed by cross-linking a redox polymer, entraps the enzymes and mediates electron transfer between the enzymes and the electrode. It is important that the enzymes are entrapped in their enzymatically active state. Should entrapment cause enzyme denaturation, the sensitivity and the selectivity of the sensor may be compromised. Synthesis of the redox polymer according to published procedures may yield a product that precipitates when added to aqueous enzyme solutions. Casting hydrogels from solutions that contain the precipitate produces microsensors with low sensitivity and selectivity, suggesting that the precipitation disrupts the structure of the enzymes. Herein, we show that a surfactant, sodium dodecyl sulfate (SDS), can prevent the precipitation and improve the sensitivity and selectivity of the sensors

  6. Entrapment Neuropathies in the Upper and Lower Limbs: Anatomy and MRI Features

    International Nuclear Information System (INIS)

    Dong, Q.; Jacobson, J.A.; Jamadar, D.A.; Gandikota, G.; Brandon, C.; Morag, Y.; Fessell, D.P.; Kim, S.M.

    2012-01-01

    Peripheral nerve entrapment occurs at specific anatomic locations. Familiarity with the anatomy and the magnetic resonance imaging (MRI) features of nerve entrapment syndromes is important for accurate diagnosis and early treatment of entrapment neuropathies. The purpose of this paper is to illustrate the normal anatomy of peripheral nerves in the upper and lower limbs and to review the MRI features of common disorders affecting the peripheral nerves, both compressive/entrapment and non compressive, involving the supra scapular nerve, the axillary nerve, the radial nerve, the ulnar nerve, and the median verve in the upper limb and the sciatic nerve, the common peroneal nerve, the tibial nerve, and the interdigital nerves in the lower limb

  7. High Generic Drug Prices and Market Competition: A Retrospective Cohort Study.

    Science.gov (United States)

    Dave, Chintan V; Kesselheim, Aaron S; Fox, Erin R; Qiu, Peihua; Hartzema, Abraham

    2017-08-01

    Prices for some generic drugs have increased in recent years, adversely affecting patients who rely on them. To determine the association between market competition levels and the change in generic drug prices in the United States. Retrospective cohort study. Prescription claims from commercial health plans between 2008 and 2013. The 5.5 years of data were divided into 11 study periods of 6 months each. The Herfindahl-Hirschman Index (HHI)-calculated by summing the squares of individual manufacturers' market shares, with higher values indicating a less competitive market-and average drug prices were estimated for the generic drugs in each period. The HHI value estimated in the baseline period (first half of 2008) was modeled as a fixed covariate. Models estimated price changes over time by level of competition, adjusting for drug shortages, market size, and dosage forms. From 1.08 billion prescription claims, a cohort of 1120 generic drugs was identified. After adjustment, drugs with quadropoly (HHI value of 2500, indicating relatively high levels of competition), duopoly (HHI value of 5000), near-monopoly (HHI value of 8000), and monopoly (HHI value of 10 000) levels of baseline competition were associated with price changes of -31.7% (95% CI, -34.4% to -28.9%), -11.8% (CI, -18.6% to -4.4%), 20.1% (CI, 5.5% to 36.6%), and 47.4% (CI, 25.4% to 73.2%), respectively, over the study period. Study findings may not be generalizable to drugs that became generic after 2008. Market competition levels were associated with a change in generic drug prices. Such measurements may be helpful in identifying older prescription drugs at higher risk for price change in the future. None.

  8. The development of high-content screening (HCS) technology and its importance to drug discovery.

    Science.gov (United States)

    Fraietta, Ivan; Gasparri, Fabio

    2016-01-01

    High-content screening (HCS) was introduced about twenty years ago as a promising analytical approach to facilitate some critical aspects of drug discovery. Its application has spread progressively within the pharmaceutical industry and academia to the point that it today represents a fundamental tool in supporting drug discovery and development. Here, the authors review some of significant progress in the HCS field in terms of biological models and assay readouts. They highlight the importance of high-content screening in drug discovery, as testified by its numerous applications in a variety of therapeutic areas: oncology, infective diseases, cardiovascular and neurodegenerative diseases. They also dissect the role of HCS technology in different phases of the drug discovery pipeline: target identification, primary compound screening, secondary assays, mechanism of action studies and in vitro toxicology. Recent advances in cellular assay technologies, such as the introduction of three-dimensional (3D) cultures, induced pluripotent stem cells (iPSCs) and genome editing technologies (e.g., CRISPR/Cas9), have tremendously expanded the potential of high-content assays to contribute to the drug discovery process. Increasingly predictive cellular models and readouts, together with the development of more sophisticated and affordable HCS readers, will further consolidate the role of HCS technology in drug discovery.

  9. Water infiltration in an aquifer recharge basin affected by temperature and air entrapment

    OpenAIRE

    Loizeau Sébastien; Rossier Yvan; Gaudet Jean-Paul; Refloch Aurore; Besnard Katia; Angulo-Jaramillo Rafael; Lassabatere Laurent

    2017-01-01

    Artificial basins are used to recharge groundwater and protect water pumping fields. In these basins, infiltration rates are monitored to detect any decrease in water infiltration in relation with clogging. However, miss-estimations of infiltration rate may result from neglecting the effects of water temperature change and air-entrapment. This study aims to investigate the effect of temperature and air entrapment on water infiltration at the basin scale by conducting successive infiltration c...

  10. Orbital Floor Fracture with Atypical Extraocular Muscle Entrapment Pattern and Intraoperative Asystole in an Adult

    Science.gov (United States)

    Merali, Farhan I.; Grant, Michael P.; Mahoney, Nicholas R.

    2015-01-01

    Extraocular muscle entrapment in a nondisplaced orbital fracture, although a well-known entity in pediatric trauma, is atypical in adults. It can present with a triad of bradycardia, nausea, and in rare cases, syncope, and result in severe fibrosis of damaged and incarcerated muscle. We present a case of muscle entrapment in a partially nondisplaced two-wall orbital fracture with accompanying preoperative bradycardia and intraoperative asystole in an adult PMID:26576246

  11. Medial collateral ligament tear entrapped within a proximal tibial physeal separation: imaging findings and operative reduction

    Energy Technology Data Exchange (ETDEWEB)

    McAnally, James L.; Eberhardt, Steven C.; Mlady, Gary W. [University of New Mexico, Department of Radiology, Albuquerque, NM (United States); Fitzpatrick, Jennifer; Bosch, Patrick [University of New Mexico, Department of Orthopaedics and Rehabilitation, Albuquerque, NM (United States)

    2008-10-15

    Entrapped soft tissues such as periosteum and tendons have been described within joints and physeal fractures in the literature and frequently result in irreducible fractures and posttraumatic growth disturbances. We believe this case represents a novel presentation of acute, preoperative, magnetic resonance (MR) imaging diagnosis of a torn medial collateral ligament entrapped within a proximal tibial physeal separation. This case is presented with MR imaging and operative correlation of the findings. (orig.)

  12. Medial collateral ligament tear entrapped within a proximal tibial physeal separation: imaging findings and operative reduction

    International Nuclear Information System (INIS)

    McAnally, James L.; Eberhardt, Steven C.; Mlady, Gary W.; Fitzpatrick, Jennifer; Bosch, Patrick

    2008-01-01

    Entrapped soft tissues such as periosteum and tendons have been described within joints and physeal fractures in the literature and frequently result in irreducible fractures and posttraumatic growth disturbances. We believe this case represents a novel presentation of acute, preoperative, magnetic resonance (MR) imaging diagnosis of a torn medial collateral ligament entrapped within a proximal tibial physeal separation. This case is presented with MR imaging and operative correlation of the findings. (orig.)

  13. Illicit drug use among rave attendees in a nationally representative sample of US high school seniors.

    Science.gov (United States)

    Palamar, Joseph J; Griffin-Tomas, Marybec; Ompad, Danielle C

    2015-07-01

    The popularity of electronic dance music and rave parties such as dance festivals has increased in recent years. Targeted samples of party-goers suggest high rates of drug use among attendees, but few nationally representative studies have examined these associations. We examined sociodemographic correlates of rave attendance and relationships between rave attendance and recent (12-month) use of various drugs in a representative sample of US high school seniors (modal age: 18) from the Monitoring the Future study (2011-2013; Weighted N=7373). One out of five students (19.8%) reported ever attending a rave, and 7.7% reported attending at least monthly. Females and highly religious students were less likely to attend raves, and Hispanics, students residing in cities, students with higher income and those who go out for fun multiple times per week were more likely to attend. Rave attendees were more likely than non-attendees to report use of an illicit drug other than marijuana (35.5% vs. 15.6%, p<0.0001). Attendees were more likely to report use of each of the 18 drugs assessed, and attendees were more likely to report more frequent use (≥6 times) of each drug (ps<0.0001). Controlling for sociodemographic covariates, frequent attendance (monthly or more often) was associated with higher odds of use of each drug (ps<0.0001). Frequent attendees were at highest risk for use of "club drugs." Findings from this study can help inform prevention and harm reduction among rave attendees at greatest risk for drug use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. IONP-doped nanoparticles for highly effective NIR-controlled drug release and combination tumor therapy

    Directory of Open Access Journals (Sweden)

    Fu X

    2017-05-01

    Full Text Available Xudong Fu,1 Xinjun Wang,1 Shaolong Zhou,1 Yanyan Zhang2 1The Fifth Affiliated Hospital of Zhengzhou University, 2School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China Abstract: Despite advances in controlled drug delivery, drug delivery systems (DDSs with controlled activated drug release and high spatial and temporal resolution are still required. Theranostic nanomedicine is capable of diagnosis, therapy, and monitoring the delivery and distribution of drug molecules and has received growing interest. In this study, a near-infrared light-controlled “off–on” DDS with magnetic resonance imaging and magnetic targeting properties was developed using a hybrid nanoplatform (carbon nanotubes [CNTs]-iron oxide nanoparticle. Doxorubicin (DOX and distearoyl-sn-glycero-3-phosphoethanolamine-PEG were adsorbed onto CNTs-iron oxide nanoparticle, and then to avoid the unexpected drug release during circulation, 1-myristyl alcohol was used to encapsulate the CNTs–drug complex. Herein, multifunctional DOX-loaded nanoparticles (NPs with “off–on” state were developed. DOX-NPs showed an obvious “off–on” effect (temperature increase, drug release controlled by near-infrared light in vitro and in vivo. In the in vivo and in vitro studies, DOX-NPs exhibited excellent magnetic resonance imaging ability, magnetic targeting property, high biosafety, and high antitumor combined therapeutic efficacy (hyperthermia combined with chemotherapy. These results highlight the great potential of DOX-NPs in the treatment of cancer. Keywords: controlled drug release, magnetic targeting, MRI, combination therapy

  15. Relationship between Individual Characteristics and High Risk Behavior in Intravenous Drug Addicts in Ardabil, 2012

    Directory of Open Access Journals (Sweden)

    Nasrin Fouladi

    2014-12-01

    Full Text Available Background & objectives: Addiction is one of the problems in world threating the social, economic and culture factors. It is essential to have an accurate knowledge about the characteristics of drug users in order to diminish the high-risk behaviors of intravenous drug addicts. This research has been done to assess relationship between individual characteristics and high risk behavior in intravenous drug addicts.   Method: In this descriptive-analytic research, 360 drug users were selected from different places in Ardabil city and interviewed by a prepared questionnaire. The data were analyzed using descriptive and analytical tests including t-test, Pearson correlation and ANOVA with SPSS statistical software.   Results: The results showed that the age, gender, material status, job position, age of addiction start, age of injection start, injection frequency, injection frequency per day, syringe supply place and the partner’s gender during recent few months had no significant difference compared to drug users with needle sharing and without needle sharing. The educational level of drug users with needle sharing was lower (P=0.037 and the number of new syringe usage per month was also lesser (P=0.001. They predicted to be more likely infected with AIDS (P=0.001 and had a less argument with their partner about using condom, also mostly have not used condom at their last sexual relationship (P=0.001. The average number of their partners during last three months was high (P=0.003 and there was a meaningful relationship between true sense of peril and using condom in drug users with needle sharing group (p=0.001.   Conclusion: There is a significant relationship between the true sense of danger and the using condom. It is necessary to have an appropriate advertising to increase using condoms among injecting drug users.

  16. Water infiltration in an aquifer recharge basin affected by temperature and air entrapment

    Directory of Open Access Journals (Sweden)

    Loizeau Sébastien

    2017-09-01

    Full Text Available Artificial basins are used to recharge groundwater and protect water pumping fields. In these basins, infiltration rates are monitored to detect any decrease in water infiltration in relation with clogging. However, miss-estimations of infiltration rate may result from neglecting the effects of water temperature change and air-entrapment. This study aims to investigate the effect of temperature and air entrapment on water infiltration at the basin scale by conducting successive infiltration cycles in an experimental basin of 11869 m2 in a pumping field at Crepieux-Charmy (Lyon, France. A first experiment, conducted in summer 2011, showed a strong increase in infiltration rate; which was linked to a potential increase in ground water temperature or a potential dissolution of air entrapped at the beginning of the infiltration. A second experiment was conducted in summer, to inject cold water instead of warm water, and also revealed an increase in infiltration rate. This increase was linked to air dissolution in the soil. A final experiment was conducted in spring with no temperature contrast and no entrapped air (soil initially water-saturated, revealing a constant infiltration rate. Modeling and analysis of experiments revealed that air entrapment and cold water temperature in the soil could substantially reduce infiltration rate over the first infiltration cycles, with respective effects of similar magnitude. Clearly, both water temperature change and air entrapment must be considered for an accurate assessment of the infiltration rate in basins.

  17. School-Based Drug Abuse Prevention Programs in High School Students

    Science.gov (United States)

    Sharma, Manoj; Branscum, Paul

    2013-01-01

    Drug abuse, or substance abuse, is a substantial public health problem in the United States, particularly among high school students. The purpose of this article was to review school-based programs implemented in high schools for substance abuse prevention and to suggest recommendations for future interventions. Included were English language…

  18. Physical and relational aggression as predictors of drug use: gender differences among high school students.

    Science.gov (United States)

    Skara, Silvana; Pokhrel, Pallav; Weiner, Michelle D; Sun, Ping; Dent, Clyde W; Sussman, Steve

    2008-12-01

    The present study investigated the longitudinal relationships between physical and relational aggression and later drug use, as moderated by gender. Self-reported data were gathered from 2064 high school students at pretest and 1-year post-test to test the hypotheses that (1) males would engage in more physical aggression than females, whereas females would engage in more relational aggression than males; and (2) physical aggression would be a stronger drug use predictor for males and relational aggression a stronger predictor for females. Results indicated that males reported engaging in more physical aggression than females at baseline; however, females and males reported engaging in similar rates of relational aggression. After controlling for relational aggression, baseline drug use, and demographic variables, physical aggression at baseline was found to predict alcohol use 1-year later for males but not for females. After controlling for physical aggression, baseline drug use, and demographic variables, relational aggression was found to predict cigarette use and marijuana use for females but not for males. However, relational aggression was found to predict later alcohol and hard drug equally across gender. These findings suggest that both physical and relational aggression are predictive of subsequent drug use and have important implications for violence and drug use prevention intervention efforts.

  19. Survey on drug use among high school students: A systematic review

    Directory of Open Access Journals (Sweden)

    Clamarta Pasuch

    2014-08-01

    Full Text Available The first experiments with drugs often occur in adolescence, in familiar surroundings, with legal substances such as alcohol and tobacco. Data indicate that adolescence is a phase of exposure and vulnerability to substance use. Objective: To determine the prevalence of drug use among high school students. Method: Systematic review. Results: We found 184 articles, and according to the exclusion criteria, 13 articles were adopted: 3 that address the theme in the South, one in the Northeast, one in the North, and the 8 in the Southeastern Brazilian regions. Discussion: We noticed a growth in drug use among adolescent students in the 13 articles examined. Research reveals significant increase in lifetime use, frequent use and heavy use of various drugs. We found that students have early contact with psychoactive substances, using them in large quantities, whether legal such as alcohol and tobacco, or illicit drugs like marijuana and solvents. The most important variable for this behavior was curiosity. Conclusion: There is an increase in substance use among high school students. Approaching the subject in schools is the best way to prevent drug use.

  20. Entrapped victims in motor vehicle collisions: characteristics and prehospital care in the city of São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Adriano Rogério Navarro Dias

    2011-01-01

    Full Text Available OBJECTIVE: To examine the severity of trauma in entrapped victims and to identify risk factors for mortality and morbidity. INTRODUCTION: Triage and rapid assessment of trauma severity is essential to provide the needed resources during prehospital and hospital phases and for outcome prediction. It is expected that entrapped victims will have greater severity of trauma and mortality than non-entrapped subjects. METHODS: A transverse, case-control, retrospective study of 1203 victims of motor vehicle collisions treated during 1 year by the prehospital service in São Paulo, Brazil was carried out. All patients were drivers, comprising 401 entrapped victims (33.3% and 802 non-entrapped consecutive controls (66.7%. Sex, age, mortality rates, Glasgow Coma Scale (GCS, Revised Trauma Score (RTS, corporal segments, timing of the prehospital care and resource use were compared between the groups. The results were analysed by χ2, Zres, analysis of variance and Bonferroni tests. RESULTS: Entrapped victims were predominantly men (84.8%, aged 32±13.1 years, with immediate mortality of 10.2% and overall mortality of 11.7%. They had a probability of death at the scene 8.2 times greater than that of non-entrapped victims. The main cause of death was hemorrhage for entrapped victims (45.2% and trauma for non-entrapped victims. Of the entrapped victims who survived, 18.7% had a severe GCS (OR = 10.62, 12% a severe RTS (OR = 9.78 and 23.7% were in shock (OR = 3.38. Entrapped victims were more commonly transported to advanced life support units and to tertiary hospitals. CONCLUSION: Entrapped victims had greater trauma severity, more blood loss and a greater mortality than respective, non-entrapped controls.

  1. High-content live cell imaging with RNA probes: advancements in high-throughput antimalarial drug discovery

    Directory of Open Access Journals (Sweden)

    Cervantes Serena

    2009-06-01

    Full Text Available Abstract Background Malaria, a major public health issue in developing nations, is responsible for more than one million deaths a year. The most lethal species, Plasmodium falciparum, causes up to 90% of fatalities. Drug resistant strains to common therapies have emerged worldwide and recent artemisinin-based combination therapy failures hasten the need for new antimalarial drugs. Discovering novel compounds to be used as antimalarials is expedited by the use of a high-throughput screen (HTS to detect parasite growth and proliferation. Fluorescent dyes that bind to DNA have replaced expensive traditional radioisotope incorporation for HTS growth assays, but do not give additional information regarding the parasite stage affected by the drug and a better indication of the drug's mode of action. Live cell imaging with RNA dyes, which correlates with cell growth and proliferation, has been limited by the availability of successful commercial dyes. Results After screening a library of newly synthesized stryrl dyes, we discovered three RNA binding dyes that provide morphological details of live parasites. Utilizing an inverted confocal imaging platform, live cell imaging of parasites increases parasite detection, improves the spatial and temporal resolution of the parasite under drug treatments, and can resolve morphological changes in individual cells. Conclusion This simple one-step technique is suitable for automation in a microplate format for novel antimalarial compound HTS. We have developed a new P. falciparum RNA high-content imaging growth inhibition assay that is robust with time and energy efficiency.

  2. Microparticulate drug delivery system containing tramadol hydrochloride for pain treatment.

    Science.gov (United States)

    Ciurba, Adriana; Todoran, Nicoleta; Vari, C E; Lazăr, Luminita; Al Hussein, Stela; Hancu, G

    2014-01-01

    The current trend of replacing conventional pharmaceutical forms is justified because most substances administered in this form give fluctuations of therapeutic concentrations and often outside the therapeutic range. In addition, these formulations offer a reduction in the dose or the number of administrations, thus increasing patient compliance. In the experiment, we developed an appropriate technology for the preparation of gelatin microspheres containing tramadol hydrochloride by emulsification/cross-linking method. The formulated microspheres were characterized by product yield, size distribution, encapsulation efficiency and in vitro release of tramadol hydrochloride. Data obtained from in vitro release studies were fitted to various mathematical models to elucidate the transport mechanisms. The kinetic models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and Hopfenberg. Spherical microspheres were obtained, with free-flowing properties. The entrapment efficiency of tramadol hydrochloride in microparticles was 79.91% and product yield -94.92%. As the microsphere size was increased, the entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for MT250-500 formulation. The gelatin microspheres had particle sizes ranging from 80 to 500 microm. The drug was released for a period of 12 hours with a maximum release of 96.02%. Of the three proposed formulations, MT250-500 presented desirable properties and optimal characteristics for the therapy of pain. Release of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because the Akaike Information Criterion had the lowest values for this kinetic model. These results suggest the opportunity to influence the therapeutic characteristics of gelatin microspheres to obtain a suitable drug delivery system for the oral administration of tramadol hydrochloride.

  3. Continuous ethanol production using immobilized yeast cells entrapped in loofa-reinforced alginate carriers

    Directory of Open Access Journals (Sweden)

    Phoowit Bangrak

    2011-06-01

    Full Text Available A culture of Saccharomyces cerevisiae M30 entrapped in loofa-reinforced alginate was used for continuous ethanol fermentation in a packed-bed reactor with initial sugar concentrations of 200-248 g/L. Maximum ethanol productivity of 11.5 g/(L·h was obtained at an ethanol concentration of 57.4 g/L, an initial sugar concentration of 220 g/L and a dilution rate (D of 0.2 h-1. However, a maximum ethanol concentration of 82.1 g/L (productivity of 9.0 g/(L·h was obtained at a D of 0.11 h-1. Ethanol productivity in the continuous culture was 6-8-fold higher than that in the batch culture. Due to the developed carrier's high biocompatibility, high porosity, and good mechanical strength, advantages such as cell regeneration, reusability, altered mechanical strength, and high capacity to trap active cells in the reactor were achieved in this study. The immobilized cell reactor was successfully operated for 30 days without any loss in ethanol productivity. The average conversion yield was 0.43-0.45 throughout the entire operation, with an immobilization yield of 47.5%. The final total cell concentration in the reactor was 37.3 g/L (17.7 g/L immobilized cells and 19.6 g/L suspended cells. The concentration of suspended cells in the effluent was 0.8 g/L.

  4. Hair Testing for Drugs of Abuse and New Psychoactive Substances in a High-Risk Population.

    Science.gov (United States)

    Salomone, Alberto; Palamar, Joseph J; Gerace, Enrico; Di Corcia, Daniele; Vincenti, Marco

    2017-06-01

    Hundreds of new psychoactive substances (NPS) have emerged in the drug market over the last decade. Few drug surveys in the USA, however, ask about use of NPS, so prevalence and correlates of use are largely unknown. A large portion of NPS use is unintentional or unknown as NPS are common adulterants in drugs like ecstasy/Molly, and most NPS are rapidly eliminated from the body, limiting efficacy of urine, blood and saliva testing. We utilized a novel method of examining prevalence of NPS use in a high-risk population utilizing hair-testing. Hair samples from high-risk nightclub and dance music attendees were tested for 82 drugs and metabolites (including NPS) using ultra-high performance liquid chromatography-tandem mass spectrometry. Eighty samples collected from different parts of the body were analyzed, 57 of which detected positive for at least one substance-either a traditional or new drug. Among these, 26 samples tested positive for at least one NPS-the most common being butylone (25 samples). Other new drugs detected include methylone, methoxetamine, 5/6-APB, α-PVP and 4-FA. Hair analysis proved a powerful tool to gain objective biological drug-prevalence information, free from possible biases of unintentional or unknown intake and untruthful reporting of use. Such testing can be used actively or retrospectively to validate survey responses and inform research on consumption patterns, including intentional and unknown use, polydrug-use, occasional NPS intake and frequent or heavy use. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Novel drugs in the management of acute mountain sickness and high altitude pulmonary edema

    OpenAIRE

    Gaurav Sikri, Gaurav; Bhattacharya,Anirban

    2015-01-01

    Gaurav Sikri, Anirban Bhattacharya Department of Physiology, Armed Forces Medical College, Wanowarie, Pune, IndiaWe read with great interest the review article titled “Wilderness medicine at high altitude: recent developments in the field” by Shah et al.1 The authors have comprehensively summarized the recent advances in the field of high altitude medicine relevant to sports and travel medicine. However, Shah et al have described potential drugs for management of high-alti...

  6. [Social network analysis and high risk behavior characteristics of recreational drug users: a qualitative study].

    Science.gov (United States)

    Wu, Di; Wang, Zhenhong; Jiang, Zhenxia; Fu, Xiaojing; Li, Hui; Zhang, Dapeng; Liu, Hui; Hu, Yifei

    2014-11-01

    To understand the characteristics of recreational drug users' behaviors and social network, as well as their potential impact to the transmission of sexual transmitted infections (STI). Qualitative interview was used to collect information on rough estimation of population size and behavior change before and after recreational drug use. A total of 120 participants were recruited by convenient sampling from April to October, 2013 in a community of Qingdao city. Blood specimens were taken for HIV/syphilis serological testing and social network analysis was performed to understand the characteristics of their behavior and social network. All participants used methamphetamine and 103 of them showed social connection. The prevalence of syphilis and HIV were 24.2% (29/120) and 2.5% (3/120) respectively. The estimated size of recreational drug users was big with a wide diversity of occupations and age range, and males were more frequent than females. Drug use may affect condom use and frequent drug users showed symptom of psychosis and neuro-toxicities. The size of social network was 2.45 ± 1.63 in the past 6 months, which indicated an increasing trend of the sexual partner number and risky behaviors. Recreational drug use could increase the size of social network among sex partners, the frequency of risky sexual behaviors and syphilis prevalence, which indicate a high risk of HIV/STI among this population as well as a huge burden of disease prevention and control in the future.

  7. Drug use Discrimination Predicts Formation of High-Risk Social Networks: Examining Social Pathways of Discrimination.

    Science.gov (United States)

    Crawford, Natalie D; Ford, Chandra; Rudolph, Abby; Kim, BoRin; Lewis, Crystal M

    2017-09-01

    Experiences of discrimination, or social marginalization and ostracism, may lead to the formation of social networks characterized by inequality. For example, those who experience discrimination may be more likely to develop drug use and sexual partnerships with others who are at increased risk for HIV compared to those without experiences of discrimination. This is critical as engaging in risk behaviors with others who are more likely to be HIV positive can increase one's risk of HIV. We used log-binomial regression models to examine the relationship between drug use, racial and incarceration discrimination with changes in the composition of one's risk network among 502 persons who use drugs. We examined both absolute and proportional changes with respect to sex partners, drug use partners, and injecting partners, after accounting for individual risk behaviors. At baseline, participants were predominately male (70%), black or Latino (91%), un-married (85%), and used crack (64%). Among those followed-up (67%), having experienced discrimination due to drug use was significantly related to increases in the absolute number of sex networks and drug networks over time. No types of discrimination were related to changes in the proportion of high-risk network members. Discrimination may increase one's risk of HIV acquisition by leading them to preferentially form risk relationships with higher-risk individuals, thereby perpetuating racial and ethnic inequities in HIV. Future social network studies and behavioral interventions should consider whether social discrimination plays a role in HIV transmission.

  8. A high efficiency, high quality and low cost internal regulated bioanalytical laboratory to support drug development needs.

    Science.gov (United States)

    Song, Yan; Dhodda, Raj; Zhang, Jun; Sydor, Jens

    2014-05-01

    In the recent past, we have seen an increase in the outsourcing of bioanalysis in pharmaceutical companies in support of their drug development pipeline. This trend is largely driven by the effort to reduce internal cost, especially in support of late-stage pipeline assets where established bioanalytical assays are used to analyze a large volume of samples. This article will highlight our perspective of how bioanalytical laboratories within pharmaceutical companies can be developed into the best partner in the advancement of drug development pipelines with high-quality support at competitive cost.

  9. A Clinical Drug Library Screen Identifies Tosufloxacin as Being Highly Active against Staphylococcus aureus Persisters

    Directory of Open Access Journals (Sweden)

    Hongxia Niu

    2015-07-01

    Full Text Available To identify effective compounds that are active against Staphylococcus aureus (S. aureus persisters, we screened a clinical drug library consisting of 1524 compounds and identified six drug candidates that had anti-persister activity: tosufloxacin, clinafloxacin, sarafloxacin, doxycycline, thiostrepton, and chlorosalicylanilide. Among them, tosufloxacin had the highest anti-persister activity, which could completely eradicate S. aureus persisters within 2 days in vitro. Clinafloxacin ranked the second with very few persisters surviving the drug exposure. Interestingly, we found that both tosufloxacin and trovafloxacin that had high activity against persisters contained at the N-1 position the 2,4-difluorophenyl group, which is absent in other less active quinolones and may be associated with the high anti-persister activity. Further studies are needed to evaluate tosufloxacin in animal models and to explain its unique activity against bacterial persisters. Our findings may have implications for improved treatment of persistent bacterial infections.

  10. Novel use of pleural ultrasound can identify malignant entrapped lung prior to effusion drainage.

    Science.gov (United States)

    Salamonsen, Matthew R; Lo, Ada K C; Ng, Arnold C T; Bashirzadeh, Farzad; Wang, William Y S; Fielding, David I K

    2014-11-01

    The presence of entrapped lung changes the appropriate management of malignant pleural effusion from pleurodesis to insertion of an indwelling pleural catheter. No methods currently exist to identify entrapped lung prior to effusion drainage. Our objectives were to develop a method to identify entrapped lung using tissue movement and deformation (strain) analysis with ultrasonography and compare it to the existing technique of pleural elastance (PEL). Prior to drainage, 81 patients with suspected malignant pleural effusion underwent thoracic ultrasound using an echocardiogram machine. Images of the atelectatic lower lobe were acquired during breath hold, allowing motion and strain related to the cardiac impulse to be analyzed using motion mode (M mode) and speckle-tracking imaging, respectively. PEL was measured during effusion drainage. The gold-standard diagnosis of entrapped lung was the consensus opinion of two interventional pulmonologists according to postdrainage imaging. Participants were randomly divided into development and validation sets. Both total movement and strain were significantly reduced in entrapped lung. Using data from the development set, the area under the receiver-operating curves for the diagnosis of entrapped lung was 0.86 (speckle tracking), 0.79 (M mode), and 0.69 (PEL). Using respective cutoffs of 6%, 1 mm, and 19 cm H2O on the validation set, the sensitivity/specificity was 71%/85% (speckle tracking), 50%/85% (M mode), and 40%/100% (PEL). This novel ultrasound technique can identify entrapped lung prior to effusion drainage, which could allow appropriate choice of definitive management (pleurodesis vs indwelling catheter), reducing the number of interventions required to treat malignant pleural effusion.

  11. [Evolution of reimbursement of high-cost anticancer drugs: Financial impact within a university hospital].

    Science.gov (United States)

    Baudouin, Amandine; Fargier, Emilie; Cerruti, Ariane; Dubromel, Amélie; Vantard, Nicolas; Ranchon, Florence; Schwiertz, Vérane; Salles, Gilles; Souquet, Pierre-Jean; Thomas, Luc; Bérard, Frédéric; Nancey, Stéphane; Freyer, Gilles; Trillet-Lenoir, Véronique; Rioufol, Catherine

    2017-06-01

    In the context of health expenses control, reimbursement of high-cost medicines with a 'minor' or 'nonexistent' improvement in actual health benefit evaluated by the Haute Autorité de santé is revised by the decree of March 24, 2016 related to the procedure and terms of registration of high-cost pharmaceutical drugs. This study aims to set up the economic impact of this measure. A six months retrospective study was conducted within a French university hospital from July 1, 2015 to December 31, 2015. For each injectable high-cost anticancer drug prescribed to a patient with cancer, the therapeutic indication, its status in relation to the marketing authorization and the associated improvement in actual health benefit were examined. The total costs of these treatments, the cost per type of indication and, in the case of marketing authorization indications, the cost per improvement in actual health benefit were evaluated considering that all drugs affected by the decree would be struck off. Over six months, 4416 high-cost injectable anticancer drugs were prescribed for a total cost of 4.2 million euros. The costs of drugs with a minor or nonexistent improvement in actual benefit and which comparator is not onerous amount 557,564 euros. The reform of modalities of inscription on the list of onerous drugs represents a significant additional cost for health institutions (1.1 million euros for our hospital) and raises the question of the accessibility to these treatments for cancer patients. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  12. Fenugreek hydrogel–agarose composite entrapped gold nanoparticles for acetylcholinesterase based biosensor for carbamates detection

    Energy Technology Data Exchange (ETDEWEB)

    Kestwal, Rakesh Mohan; Bagal-Kestwal, Dipali; Chiang, Been-Huang, E-mail: bhchiang@ntu.edu.tw

    2015-07-30

    A biosensor was fabricated to detect pesticides in food samples. Acetylcholinesterase was immobilized in a novel fenugreek hydrogel–agarose matrix with gold nanoparticles. Transparent thin films with superior mechanical strength and stability were obtained with 2% fenugreek hydrogel and 2% agarose. Immobilization of acetylcholinesterase on the membrane resulted in high enzyme retention efficiency (92%) and a significantly prolonged shelf life of the enzyme (half-life, 55 days). Transmission electron microscopy revealed that, gold nanoparticles (10–20 nm in diameter) were uniformly dispersed in the fenugreek hydrogel–agarose–acetylcholinesterase membrane. This immobilized enzyme-gold nanoparticle dip-strip system detected various carbamates, including carbofuran, oxamyl, methomyl, and carbaryl, with limits of detection of 2, 21, 113, and 236 nM (S/N = 3), respectively. Furthermore, the fabricated biosensor exhibited good testing capabilities when used to detect carbamates added to various fruit and vegetable samples. - Highlights: • Acetylcholinesterase (AChE) dip-strip biosensor fabricated to detect carbamates. • AChE entrapped in fenugreek hydrogel–agarose matrix with gold nanoparticles (GNPs). • High enzyme retention efficiency (92%) and shelf life (half-life, 55 days). • Detection limits of carbofuran, oxamyl and methomyl: 2, 21 and 113 nM. • The biosensor had good testing capabilities to detect carbamates in food samples.

  13. Cytotoxic Drugs Departments as a precondition for high-quality product

    Directory of Open Access Journals (Sweden)

    Katarzyna Głuszek

    2014-06-01

    a pharmacy becomes the producer and distributor of oncologic drugs. This is related with high requirements concerning the production of drugs (high quality, safety of the engaged staff, as well as participation in a rational management of medicines. According to the FIP, a pharmacy is a public health care facility where work is performed by authorised persons: Masters of Pharmacy and pharmacy technicians. At present the task of a clinical pharmacist also includes the supervision of activities in the area of clinical pharmacy. This is a new task for pharmacists, who are obliged to constantly expand their knowledge and actively participate in the activities of the medical team.

  14. 3D printing of high drug loaded dosage forms using thermoplastic polyurethanes.

    Science.gov (United States)

    Verstraete, G; Samaro, A; Grymonpré, W; Vanhoorne, V; Van Snick, B; Boone, M N; Hellemans, T; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2018-01-30

    It was the aim of this study to develop high drug loaded (>30%, w/w), thermoplastic polyurethane (TPU)-based dosage forms via fused deposition modelling (FDM). Model drugs with different particle size and aqueous solubility were pre-processed in combination with diverse TPU grades via hot melt extrusion (HME) into filaments with a diameter of 1.75 ± 0.05 mm. Subsequently, TPU-based filaments which featured acceptable quality attributes (i.e. consistent filament diameter, smooth surface morphology and good mechanical properties) were printed into tablets. The sustained release potential of the 3D printed dosage forms was tested in vitro. Moreover, the impact of printing parameters on the in vitro drug release was investigated. TPU-based filaments could be loaded with 60% (w/w) fine drug powder without observing severe shark skinning or inconsistent filament diameter. During 3D printing experiments, HME filaments based on hard TPU grades were successfully converted into personalized dosage forms containing a high concentration of crystalline drug (up to 60%, w/w). In vitro release kinetics were mainly affected by the matrix composition and tablet infill degree. Therefore, this study clearly demonstrated that TPU-based FDM feedstock material offers a lot of formulation freedom for the development of personalized dosage forms. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Entrapment of Bacteriocin 105B onto Fabric with Titania

    Science.gov (United States)

    2017-02-09

    drug resistant strains of bacteria via the unintentional selection of strains which are resistant to the antimicrobial (Tattawasart et al. 1999, Thomas... antimicrobial yields a bacterial pool comprised of predominantly resistant strains, rendering the broad-spectrum antimicrobial ineffective (Levy et al. 2004...Application of a new broad-spectrum antimicrobial to control the strains developing resistance to the original drug leads to further enrichment of

  16. FACTORS AFFECTING THE RELEASE RATE OF A HIGHLY SOLUBLE DRUG FROM A PROGRAMMED RELEASE MEGALOPOROUS SYSTEM

    NARCIS (Netherlands)

    VANDERVEEN, C; MENGER, NR; LERK, CF

    The present study reports on the successful incorporation of a highly soluble drug, procaine HCl, in a programmed-release megaloporous system. This solid two-phase system is composed of housing phase matrix granules (HMG), controlling liquid penetration into the system, and of restraining phase

  17. [From the discovery of antibiotics to emerging highly drug-resistant bacteria].

    Science.gov (United States)

    Meunier, Olivier

    2015-01-01

    The discovery of antibiotics has enabled serious infections to be treated. However, bacteria resistant to several families of antibiotics and the emergence of new highly drug-resistant bacteria constitute a public health issue in France and across the world. Actions to prevent their transmission are being put in place. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  18. Cage-Like Porous Carbon with Superhigh Activity and Br2 -Complex-Entrapping Capability for Bromine-Based Flow Batteries.

    Science.gov (United States)

    Wang, Chenhui; Lai, Qinzhi; Xu, Pengcheng; Zheng, Daoyuan; Li, Xianfeng; Zhang, Huamin

    2017-06-01

    Bromine-based flow batteries receive wide attention in large-scale energy storage because of their attractive features, such as high energy density and low cost. However, the Br 2 diffusion and relatively low activity of Br 2 /Br - hinder their further application. Herein, a cage-like porous carbon (CPC) with specific pore structure combining superhigh activity and Br 2 -complex-entrapping capability is designed and fabricated. According to the results of density functional theory (DFT) calculation, the pore size of the CPC (1.1 nm) is well designed between the size of Br - (4.83 Å), MEP + (9.25 Å), and Br 2 complex (MEPBr 3 12.40 Å), wherein Br - is oxidized to Br 2 , which forms a Br 2 complex with the complexing agent immediately and is then entrapped in the cage via pore size exclusion. In addition, the active sites produced during the carbon dioxide activation process dramatically accelerate the reaction rate of Br 2 /Br - . In this way, combining a high Br 2 -entrapping-capability and high specific surface areas, the CPC shows very impressive performance. The zinc bromine flow battery assembled with the prepared CPC shows a Coulombic efficiency of 98% and an energy efficiency of 81% at the current density of 80 mA cm -2 , which are among the highest values ever reported. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Entrapping quercetin in silica/polyethylene glycol hybrid materials: Chemical characterization and biocompatibility

    Energy Technology Data Exchange (ETDEWEB)

    Catauro, Michelina, E-mail: michelina.catauro@unina2.it [Department of Industrial and Information Engineering, Second University of Naples, Via Roma 29, 81031 Aversa (Italy); Bollino, Flavia [Department of Industrial and Information Engineering, Second University of Naples, Via Roma 29, 81031 Aversa (Italy); Nocera, Paola; Piccolella, Simona; Pacifico, Severina [Department Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Via Vivaldi 43, 81100 Caserta (Italy)

    2016-11-01

    Sol-gel synthesis was exploited to entrap quercetin, a natural occurring antioxidant polyphenol, in silica-based hybrid materials, which differed in their polyethylene glycol (PEG) content (6, 12, 24 and 50 wt%). The materials obtained, whose nano-composite nature was ascertained by Scanning Electron Microscopy (SEM), were chemically characterized by Fourier Transform InfraRed (FT-IR) and UV-Vis spectroscopies. The results prove that a reaction between the polymer and the drug occurred. Bioactivity tests showed their ability to induce hydroxyapatite nucleation on the sample surfaces. The direct contact method was applied to screen the cytotoxicity of the synthetized materials towards fibroblast NIH 3T3 cells, commonly used for in vitro biocompatibility studies, and three nervous system cell lines (neuroblastoma SH-SY5Y, glioma U251, and pheochromocytoma PC12 cell lines), adopted as models in oxidative stress related studies. Using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay NIH 3T3 proliferation was assessed and the morphology was not compromised by direct exposure to the materials. Analogously, PC-12, and U-251 cell lines were not affected by new materials. SH-SY5Y appeared to be the most sensitive cell line with cytotoxic effects of 20–35%. - Highlights: • SiO{sub 2}/PEG quercetin organic-inorganic hybrids were synthesized via sol-gel. • The formation of apatite on materials surface after SBF proved their bioactivity. • Viability of NIH-3T3 cells was significantly increased by exposure to the hybrids. • Viability of PC-12 and U-251 cell lines was not affected by new materials. • SH-SY5Y cell proliferation was inhibited and their morphology was changed by hybrids.

  20. Treatment of acetone waste gases using slurry-phase airlift embedded with polyacrylamide-entrapped cell beads.

    Science.gov (United States)

    Hwang, Sz-Chwun John; Lin, Yun-Huin; Huang, Ku Shu; Lyuu, Jyuhn-Yih; Hou, Cheng-Ting; Chen, Hsin-Hua; He, Sin-Yi

    2009-10-01

    Acetone is the most common chemical used in the Hsin-chu Science Park in Taiwan. The three-phase airlift bioreactor was designed to absorb acetone into the 39 L of medium solution and then degraded by 2-L polyacrylamide (PAA)-entrapped Thiosphaera pantotropha cell beads. The airlift medium was successfully regenerated and circulated for more than 5 months. The elimination capacity of 350-part per million (ppm) acetone at 10 L x min(-1) was 258.4 g x m(-3) hr(-1) (160.4 g-C x m(-3) hr(-1)) with 100% removal efficiency in Stage II, higher than previously reported biofiltration results. The maximum chemical oxygen demand:nitrogen ratio of 100:2.9 is achieved, and a balanced nutrient state was indicated by the change in redox potential. The pH of the system was maintained at neutral because of the strong buffer agent added to the medium (final buffer intensity, beta = 1.18 x 10(-2) M). The PAA-entrapped cell beads could also provide a good barrier for high salinity gradient environment and the inoculum source to maintain steady operation of the system.

  1. Optimisation of nutritional requirements for dopamine synthesis by calcium alginate-entrapped mutant strain of Aspergillus oryzae EMS-6.

    Science.gov (United States)

    Ali, Sikander; Nawaz, Wajeeha

    2017-02-01

    The optimisation of nutritional requirements for dopamine (DA) synthesis by calcium alginate-entrapped mutant variant of Aspergillus oryzae EMS-6 using submerged fermentation technique was investigated. A total of 13 strains were isolated from soil. Isolate I-2 was selected as a better producer of DA and improved by exposing with ethyl methylsulphonate (EMS). EMS-6 was selected as it exhibited 43 μg/mL DA activity. The mutant variable was further treated with low levels of l-cysteine HCl to make it resistant against diversion and environmental stress. The conidiospores of mutant variant were entrapped in calcium alginate beads for stable product formation. EMS-6 gave maximum DA activity (124 μg/mL) when supplemented with 0.1% peptone and 0.2% sucrose, under optimised parameters viz. pH 3, temperature of 55 °C and incubation time of 70 min. The study involves the high profile of DA activity and is needed, as DA is capable to control numerous neurogenic disorders.

  2. Origin and Distribution of Methane Entrapped in Calcareous Alpine Proglacial Soil

    Science.gov (United States)

    Zhu, Biqing; Schroth, Martin H.; Henneberger, Ruth; Kübler, Manuel; Zeyer, Josef

    2017-04-01

    Methane (CH4) is an important greenhouse gas. The atmospheric methane concentration has been increasing in recent years, which is caused by imbalance between sources and sinks. Methane has been recently discovered to be entrapped in calcareous Swiss Alpine proglacial soil. This CH4 can be released upon mechanical impact and acidification. However, the amount, distribution and environmental fate of this entrapped CH4 in proglacial environment remain unknown. The entrapped CH4 in proglacial soil may be of modern or ancient origin. Modern origin includes ongoing or recent microbial CH4 production (methanogenesis) in subglacial or proglacial environments. An ancient origin mainly refers to CH4 produced thermogenically. This soil entrapped CH4 might be a common phenomenon along the entire glacial forefield, or it might only be present at few locations and depth. We present results of studies from two Swiss Alpine Glacier catchments, Wildstrubel Glacier (Canton Valais) and the Griessfirn Glacier (Canton Uri). Our main goals were 1) to assess the origin of CH4 entrapped in various glacial environments (subglacial, proglacial and supraglacial, soil and bedrocks) using geochemical and microbiological evidence; 2) to assess the spatial distribution of entrapped CH4. We performed geochemical analysis (CH4 content, gas wetness ([C1]/[C2-C3] alkane ratio), CH4 stable 13C- and 2H-isotopes, TOC) on subglacial, proglacial, and supraglacial soil samples collected from well-aerated and water-logged locations. Geochemical analysis was also selectively conducted on pore-water samples and on rock samples collected from different geological formations along the catchments. We also performed batch incubations on soil samples collected from subglacial, proglacial water-logged and supraglacial zones. In addition, for the aforementioned three types of samples, we also performed molecular analyses targeting the mcrA gene, which encodes the α-subunit of the enzyme methyl-coenzyme M reductase

  3. Nanoparticles with high payloads of pipemidic acid, a poorly soluble crystalline drug: drug-initiated polymerization and self-assembly approach

    Directory of Open Access Journals (Sweden)

    Elisabetta Pancani

    2018-05-01

    Full Text Available Nowadays, biodegradable polymers such as poly(lactic acid (PLA, poly(D,L-lactic-co-glycolic acid (PLGA and poly(ε-caprolactone (PCL remain the most common biomaterials to produce drug-loaded nanoparticles (NPs. Pipemidic acid (PIP is a poorly soluble antibiotic with a strong tendency to crystallize. PIP incorporation in PLA/PLGA NPs was challenging because of PIP crystals formation and burst release. As PIP had a poor affinity for the NPs, an alternative approach to encapsulation was used, consisting in coupling PIP to PCL. Thus, a PCL–PIP conjugate was successfully synthesized by an original drug-initiated polymerization in a single step without the need of catalyst. PCL–PIP was characterized by NMR, IR, SEC and mass spectrometry. PCL–PIP was used to prepare self-assembled NPs with PIP contents as high as 27% (w/w. The NPs were characterized by microscopy, DLS, NTA and TRPS. This study paves the way towards the production of NPs with high antibiotic payloads by drug-initiated polymerization. Further studies will deal with the synthesis of novel polymer–PIP conjugates with ester bonds between the drug and PCL. PIP can be considered as a model drug and the strategy developed here could be extended to other challenging antibiotics or anticancer drugs and employed to efficiently incorporate them in NPs. KEY WORDS: Pipemidic acid, Nanoparticle, Antibiotic, Nanoprecipitation, Crystalline drug, Drug-initiated   polymerization

  4. Generation of drugs coated iron nanoparticles through high energy ball milling

    Energy Technology Data Exchange (ETDEWEB)

    Radhika Devi, A.; Murty, B. S. [Department of Metallurgical and Materials Engineering, Indian Institute of Technology Madras, Chennai 600036 (India); Chelvane, J. A. [Defence Metallurgical Research Laboratory, Hyderabad 500058 (India); Prabhakar, P. K.; Padma Priya, P. V.; Doble, Mukesh [Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036 (India)

    2014-03-28

    The iron nanoparticles coated with oleic acid and drugs such as folic acid/Amoxicillin were synthesized by high energy ball milling and characterized by X-ray diffraction, Transmission electron microscope, zeta potential, dynamic light scattering, Fourier Transform Infra red (FT-IR) measurements, and thermo gravimetric analysis (TGA). FT-IR and TGA measurements show good adsorption of drugs on oleic acid coated nanoparticles. Magnetic measurements indicate that saturation magnetization is larger for amoxicillin coated particles compared to folic acid coated particles. The biocompatibility of the magnetic nanoparticles prepared was evaluated by in vitro cytotoxicity assay using L929 cells as model cells.

  5. Entrapment of Probiotics in Water Extractable Arabinoxylan Gels: Rheological and Microstructural Characterization

    Directory of Open Access Journals (Sweden)

    Adriana Morales-Ortega

    2014-03-01

    Full Text Available Due to their porous structure, aqueous environment and dietary fiber nature arabinoxylan (AX gels could have potential applications for colon-specific therapeutic molecule delivery. In addition, prebiotic and health related effects of AX have been previously demonstrated. It has been also reported that cross-linked AX can be degraded by bacteria from the intestinal microbiota. However, AX gels have not been abundantly studied as carrier systems and there is no information available concerning their capability to entrap cells. In this regard, probiotic bacteria such as Bifidobacterium longum have been the focus of intense research activity lately. The objective of this research was to investigate the entrapment of probiotic B. longum in AX gels. AX solution at 2% (w/v containing B. longum (1 × 107 CFU/cm formed gels induced by laccase as cross-linking agent. The entrapment of B. longum decreased gel elasticity from 31 to 23 Pa, probably by affecting the physical interactions taking place between WEAX chains. Images of AX gels containing B. longum viewed under a scanning electron microscope show the gel network with the bacterial cells entrapped inside. The microstructure of these gels resembles that of an imperfect honeycomb. The results suggest that AX gels can be potential candidates for the entrapment of probiotics.

  6. No Way Out: Entrapment as a Moderator of Suicide Ideation Among Military Personnel.

    Science.gov (United States)

    Shelef, Leah; Levi-Belz, Yossi; Fruchter, Eyal; Santo, Yoav; Dahan, Eyal

    2016-10-01

    Suicide is a leading and growing cause of death in the military during peacetime. This study sought to examine the psychological mechanisms relating to entrapment, stress, and psychological protective factors facilitating suicide ideation among military personnel. The study population comprised 168 soldiers (aged 18-21) divided into 3 groups: suicide attempters (n = 58), those receiving treatment by a mental health professional, reporting no suicidal behavior (n = 58), and controls (n = 50). In general, the suicidal group scored higher than the 2 other groups in stress levels and entrapment but lower than the other 2 groups in perceived problem-solving abilities and perceived social support. Moreover, the interaction of stress and entrapment predict suicide ideation beyond stress, protective factors, and entrapment alone. Entrapment is an important predictor of suicide ideation and can serve as a moderator, in that its presence may exacerbate the harsh situation of subjective stress within the military context and intensify it into a suicide risk. © 2016 Wiley Periodicals, Inc.

  7. Antioxidant activities and skin hydration effects of rice bran bioactive compounds entrapped in niosomes.

    Science.gov (United States)

    Manosroi, Aranya; Chutoprapat, Romchat; Sato, Yuji; Miyamoto, Kukizo; Hsueh, Kesyin; Abe, Masahiko; Manosroi, Worapaka; Manosroi, Jiradej

    2011-03-01

    Bioactive compounds [ferulic acid (F), gamma-oryzanol (O) and phytic acid (P)] in rice bran have been widely used as antioxidants in skin care products. However, one of the major problems of antioxidants is the deterioration of their activities during long exposure to air and light. Niosomes have been used to entrap many degradable active agents not only for stability improvement, but also for increasing skin hydration. The objective of this study was to determine antioxidant activities [by in vitro ORAC (oxygen radical absorbance capacity) and ex vivo lipid peroxidation inhibition assay] and in vivo human skin hydration effects of gel and cream containing the rice bran extracts entrapped in niosomes. Gel and cream containing the rice bran extracts entrapped in niosomes showed higher antioxidant activity (ORAC value) at 20-28 micromol of Trolox equivalents (TE) per gram of the sample than the placebo gel and cream which gave 16-18 micromolTE/g. Human sebum treated with these formulations showed more lipid peroxidation inhibition activity than with no treatment of about 1.5 times. The three different independent techniques including corneometer, vapometer and confocal Raman microspectroscopy (CRM) indicated the same trend in human skin hydration enhancement of the gel or cream formulations containing the rice bran extracts entrapped in niosomes of about 20, 3 and 30%, respectively. This study has demonstrated the antioxidant activities and skin hydration enhancement of the rice bran bioactive compounds when entrapped in niosomes and incorporated in cream formulations.

  8. The NARCONON™ drug education curriculum for high school students: A non-randomized, controlled prevention trial

    Directory of Open Access Journals (Sweden)

    Cecchini Marie A

    2008-03-01

    Full Text Available Abstract Background An estimated 13 million youths aged 12 to 17 become involved with alcohol, tobacco and other drugs annually. The number of 12- to 17-year olds abusing controlled prescription drugs increased an alarming 212 percent between 1992 and 2003. For many youths, substance abuse precedes academic and health problems including lower grades, higher truancy, drop out decisions, delayed or damaged physical, cognitive, and emotional development, or a variety of other costly consequences. For thirty years the Narconon program has worked with schools and community groups providing single educational modules aimed at supplementing existing classroom-based prevention activities. In 2004, Narconon International developed a multi-module, universal prevention curriculum for high school ages based on drug abuse etiology, program quality management data, prevention theory and best practices. We review the curriculum and its rationale and test its ability to change drug use behavior, perceptions of risk/benefits, and general knowledge. Methods After informed parental consent, approximately 1000 Oklahoma and Hawai'i high school students completed a modified Center for Substance Abuse Prevention (CSAP Participant Outcome Measures for Discretionary Programs survey at three testing points: baseline, one month later, and six month follow-up. Schools assigned to experimental conditions scheduled the Narconon curriculum between the baseline and one-month follow-up test; schools in control conditions received drug education after the six-month follow-up. Student responses were analyzed controlling for baseline differences using analysis of covariance. Results At six month follow-up, youths who received the Narconon drug education curriculum showed reduced drug use compared with controls across all drug categories tested. The strongest effects were seen in all tobacco products and cigarette frequency followed by marijuana. There were also significant

  9. High fat diet and GLP-1 drugs induce pancreatic injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron; Zhang, Jun

    2014-04-15

    Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.

  10. High fat diet and GLP-1 drugs induce pancreatic injury in mice

    International Nuclear Information System (INIS)

    Rouse, Rodney; Xu, Lin; Stewart, Sharron; Zhang, Jun

    2014-01-01

    Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment

  11. The relation of self-esteem and illegal drug usage in high school students.

    Science.gov (United States)

    Khajehdaluee, Mohammad; Zavar, Abbas; Alidoust, Mahbobeh; Pourandi, Razieh

    2013-11-01

    Adolescence is the period of stress and strain. Researchers have shown that adolescents without strong social supports would have tendency towards smoking and drug abuse. This study aimed to evaluate the relationship between low self-esteem and illegal drug abuse. Participants were 943 grades nine to 12 high school students, from Sarakhs during 2010 - 2011. Adolescents participated in the study, completed two self-report questionnaires. The first questionnaire included questions about individual and family information, smoking and illegal drug abuse history, and the second was the Rosenberg's self-esteem scale. 53.8% of participants were male (507 individuals). The mean Rosenberg self-esteem score was 19.8 + 5.2, and the most frequent obtained scores were from 22 to 30. The difference of Rosenberg self-esteem score test between students who did not use any substance and those who had a history of smoking or drug abuse like heroin, pills, alcohols, betel nut (Nas) and other drugs (such as Pan and Hookah) was significant (P self-esteem scores between adolescents who lived with both or one of the parents, and those who did not live with any of parents, was significant (P = 0.04). There was also a significant association between the number of children in the family and self-esteem score. The current study showed significant association between the Rosenberg self-esteem test results and smoking, and illegal drug abuse like heroin, pills, alcohol, Nas, and other substances. Therefore, increasing self-esteem is essential for preventing the adolescents' emotional and behavioral disorders. This fact could guide us to the new approaches for smoking and drug-abuse prevention in adolescents.

  12. Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

    International Nuclear Information System (INIS)

    Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan; Durmus, Naside Gozde

    2011-01-01

    Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

  13. Microengineering methods for cell-based microarrays and high-throughput drug-screening applications

    Energy Technology Data Exchange (ETDEWEB)

    Xu Feng; Wu Jinhui; Wang Shuqi; Gurkan, Umut Atakan; Demirci, Utkan [Department of Medicine, Demirci Bio-Acoustic-MEMS in Medicine (BAMM) Laboratory, Center for Biomedical Engineering, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA (United States); Durmus, Naside Gozde, E-mail: udemirci@rics.bwh.harvard.edu [School of Engineering and Division of Biology and Medicine, Brown University, Providence, RI (United States)

    2011-09-15

    Screening for effective therapeutic agents from millions of drug candidates is costly, time consuming, and often faces concerns due to the extensive use of animals. To improve cost effectiveness, and to minimize animal testing in pharmaceutical research, in vitro monolayer cell microarrays with multiwell plate assays have been developed. Integration of cell microarrays with microfluidic systems has facilitated automated and controlled component loading, significantly reducing the consumption of the candidate compounds and the target cells. Even though these methods significantly increased the throughput compared to conventional in vitro testing systems and in vivo animal models, the cost associated with these platforms remains prohibitively high. Besides, there is a need for three-dimensional (3D) cell-based drug-screening models which can mimic the in vivo microenvironment and the functionality of the native tissues. Here, we present the state-of-the-art microengineering approaches that can be used to develop 3D cell-based drug-screening assays. We highlight the 3D in vitro cell culture systems with live cell-based arrays, microfluidic cell culture systems, and their application to high-throughput drug screening. We conclude that among the emerging microengineering approaches, bioprinting holds great potential to provide repeatable 3D cell-based constructs with high temporal, spatial control and versatility.

  14. Novel drugs in the management of acute mountain sickness and high altitude pulmonary edema

    Directory of Open Access Journals (Sweden)

    Sikri G

    2015-12-01

    Full Text Available Gaurav Sikri, Anirban Bhattacharya Department of Physiology, Armed Forces Medical College, Wanowarie, Pune, IndiaWe read with great interest the review article titled “Wilderness medicine at high altitude: recent developments in the field” by Shah et al.1 The authors have comprehensively summarized the recent advances in the field of high altitude medicine relevant to sports and travel medicine. However, Shah et al have described potential drugs for management of high-altitude illnesses, such as acute mountain sickness (AMS, high altitude cerebral edema, and high altitude pulmonary edema (HAPE as one group under the section “Novel drug treatment for AMS”. The pathophysiologies of these two sets of diseases (AMS/high altitude cerebral edema as one and HAPE as another set are different2 and hence it would have been nice to have had the novel drugs described separately to elucidate the therapeutic approach for the two different classes of diseases.View original paper by Shah et al.

  15. Letter: Entrapment and interaction of an air bubble with an oscillating cavitation bubble

    Science.gov (United States)

    Kannan, Y. S.; Karri, Badarinath; Sahu, Kirti Chandra

    2018-04-01

    The mechanism of the formation of an air bubble due to an oscillating cavitation bubble in its vicinity is reported from an experimental study using high-speed imaging. The cavitation bubble is created close to the free surface of water using a low-voltage spark circuit comprising two copper electrodes in contact with each other. Before the bubble is created, a third copper wire is positioned in contact with the free surface of water close to the two crossing electrodes. Due to the surface tension at the triple point (wire-water-air) interface, a small dip is observed in the free surface at the point where the wire is immersed. When the cavitation bubble is created, the bubble pushes at the dip while expanding and pulls at it while collapsing. The collapse phase leads to the entrapment of an air bubble at the wire immersion point. During this phase, the air bubble undergoes a "catapult" effect, i.e., it expands to a maximum size and then collapses with a microjet at the free surface. To the best of our knowledge, this mechanism has not been reported so far. A parametric study is also conducted to understand the effects of wire orientation and bubble distance from the free surface.

  16. In vitro drug response and efflux transporters associated with drug resistance in pediatric high grade glioma and diffuse intrinsic pontine glioma.

    Directory of Open Access Journals (Sweden)

    Susanna J E Veringa

    Full Text Available Pediatric high-grade gliomas (pHGG, including diffuse intrinsic pontine gliomas (DIPG, are the leading cause of cancer-related death in children. While it is clear that surgery (if possible, and radiotherapy are beneficial for treatment, the role of chemotherapy for these tumors is still unclear. Therefore, we performed an in vitro drug screen on primary glioma cells, including three DIPG cultures, to determine drug sensitivity of these tumours, without the possible confounding effect of insufficient drug delivery. This screen revealed a high in vitro cytotoxicity for melphalan, doxorubicine, mitoxantrone, and BCNU, and for the novel, targeted agents vandetanib and bortezomib in pHGG and DIPG cells. We subsequently determined the expression of the drug efflux transporters P-gp, BCRP1, and MRP1 in glioma cultures and their corresponding tumor tissues. Results indicate the presence of P-gp, MRP1 and BCRP1 in the tumor vasculature, and expression of MRP1 in the glioma cells themselves. Our results show that pediatric glioma and DIPG tumors per se are not resistant to chemotherapy. Treatment failure observed in clinical trials, may rather be contributed to the presence of drug efflux transporters that constitute a first line of drug resistance located at the blood-brain barrier or other resistance mechanism. As such, we suggest that alternative ways of drug delivery may offer new possibilities for the treatment of pediatric high-grade glioma patients, and DIPG in particular.

  17. Polymer-free Drug-Coated Coronary Stents in Patients at High Bleeding Risk

    DEFF Research Database (Denmark)

    Urban, Philip; Meredith, Ian T; Abizaid, Alexandre

    2015-01-01

    BACKGROUND: Patients at high risk for bleeding who undergo percutaneous coronary intervention (PCI) often receive bare-metal stents followed by 1 month of dual antiplatelet therapy. We studied a polymer-free and carrier-free drug-coated stent that transfers umirolimus (also known as biolimus A9......), a highly lipophilic sirolimus analogue, into the vessel wall over a period of 1 month. METHODS: In a randomized, double-blind trial, we compared the drug-coated stent with a very similar bare-metal stent in patients with a high risk of bleeding who underwent PCI. All patients received 1 month of dual...... ratio, 0.50; 95% CI, 0.37 to 0.69; Pbleeding who underwent PCI, a polymer-free umirolimus-coated stent was superior to a bare-metal stent with respect to the primary safety and efficacy end points when used with a 1-month course of dual antiplatelet...

  18. Fabrication of high specificity hollow mesoporous silica nanoparticles assisted by Eudragit for targeted drug delivery.

    Science.gov (United States)

    She, Xiaodong; Chen, Lijue; Velleman, Leonora; Li, Chengpeng; Zhu, Haijin; He, Canzhong; Wang, Tao; Shigdar, Sarah; Duan, Wei; Kong, Lingxue

    2015-05-01

    Hollow mesoporous silica nanoparticles (HMSNs) are one of the most promising carriers for effective drug delivery due to their large surface area, high volume for drug loading and excellent biocompatibility. However, the non-ionic surfactant templated HMSNs often have a broad size distribution and a defective mesoporous structure because of the difficulties involved in controlling the formation and organization of micelles for the growth of silica framework. In this paper, a novel "Eudragit assisted" strategy has been developed to fabricate HMSNs by utilising the Eudragit nanoparticles as cores and to assist in the self-assembly of micelle organisation. Highly dispersed mesoporous silica spheres with intact hollow interiors and through pores on the shell were fabricated. The HMSNs have a high surface area (670 m(2)/g), small diameter (120 nm) and uniform pore size (2.5 nm) that facilitated the effective encapsulation of 5-fluorouracil within HMSNs, achieving a high loading capacity of 194.5 mg(5-FU)/g(HMSNs). The HMSNs were non-cytotoxic to colorectal cancer cells SW480 and can be bioconjugated with Epidermal Growth Factor (EGF) for efficient and specific cell internalization. The high specificity and excellent targeting performance of EGF grafted HMSNs have demonstrated that they can become potential intracellular drug delivery vehicles for colorectal cancers via EGF-EGFR interaction. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Entrapment of Guide Wire in an Inferior Vena Cava Filter: A Technique for Removal

    International Nuclear Information System (INIS)

    Abdel-Aal, Ahmed Kamel; Saddekni, Souheil; Hamed, Maysoon Farouk; Fitzpatrick, Farley

    2013-01-01

    Entrapment of a central venous catheter (CVC) guide wire in an inferior vena cava (IVC) filter is a rare, but reported complication during CVC placement. With the increasing use of vena cava filters (VCFs), this number will most likely continue to grow. The consequences of this complication can be serious, as continued traction upon the guide wire may result in filter dislodgement and migration, filter fracture, or injury to the IVC. We describe a case in which a J-tipped guide wire introduced through a left subclavian access without fluoroscopic guidance during CVC placement was entrapped at the apex of an IVC filter. We describe a technique that we used successfully in removing the entrapped wire through the left subclavian access site. We also present simple useful recommendations to prevent this complication.

  20. Optimizing the Production of Biodiesel Using Lipase Entrapped in Biomimetic Silica

    Energy Technology Data Exchange (ETDEWEB)

    I-Ching Kuan; Chia-Chi Lee; Bing-Hong Tsai; Shiow-Ling Lee; Wei-Ting Lee; Chi-Yang Yu [Department of Bioengineering, Tatung Univ., Taipei, Taiwan (China)

    2013-04-15

    We entrapped lipase from Pseudomonas cepacia in polyallylamine-mediated biomimetic silica, and then applied entrapped lipase to the synthesis of biodiesel with soybean oil or waste cooking oil as a feedstock. The effects of reaction temperature, substrate molar ratio (methanol/oil) and n-hexane content (w/w of oil) were evaluated using response surface methodology (RSM) combined with Box-Behnken design. The optimal reaction conditions for soybean oil were 43.6 deg C, substrate molar ratio of 4.3%, and 75% n-hexane. The predicted and experimental values of biodiesel conversion were 79% and 76%, respectively. The optimal reaction conditions for waste cooking oil were 43.3 deg C, substrate molar ratio of 5%, and 38% n-hexane. The predicted and experimental values of conversion were 68% and 67%, respectively. The conversion efficiency remained the same even after 1-month storage of entrapped lipase at 4 deg C or room temperature.

  1. A multilayer microdevice for cell-based high-throughput drug screening

    International Nuclear Information System (INIS)

    Liu, Chong; Wang, Lei; Li, Jingmin; Ding, Xiping; Chunyu, Li; Xu, Zheng; Wang, Qi

    2012-01-01

    A multilayer polydimethylsiloxane microdevice for cell-based high-throughput drug screening is described in this paper. This established microdevice was based on a modularization method and it integrated a drug/medium concentration gradient generator (CGG), pneumatic microvalves and a cell culture microchamber array. The CGG was able to generate five steps of linear concentrations with the same outlet flow rate. The medium/drug flowed through CGG and then into the pear-shaped cell culture microchambers vertically. This vertical perfusion mode was used to reduce the impact of the shear stress on the physiology of cells induced by the fluid flow in the microchambers. Pear-shaped microchambers with two arrays of miropillars at each outlet were adopted in this microdevice, which were beneficial to cell distribution. The chemotherapeutics Cisplatin (DDP)-induced Cisplatin-resistant cell line A549/DDP apoptotic experiments were performed well on this platform. The results showed that this novel microdevice could not only provide well-defined and stable conditions for cell culture, but was also useful for cell-based high-throughput drug screening with less reagents and time consumption. (paper)

  2. Drug interactions in HIV patients treated in a high complexity hospital of Antofagasta city

    Directory of Open Access Journals (Sweden)

    Patricio R. Araya

    2017-11-01

    Full Text Available Context: From the beginning of the global HIV epidemic there has been a great concern about drug interactions (DI considering that up to 27% of all patients may be affected by at least one type of DI, this risk increases by receiving concomitant treatments. This DI leads to negative consequences such as adverse drug reactions (ADR, lack of treatment adherence and new hospital admissions. Aims: To determine the prevalence of DI of antiretroviral drugs and their clinical consequences in UNACESS-VIH-SIDA patients of Hospital Regional de Antofagasta. Methods: The study included a total of 100 HIV patients. To identify DI, Micromedex database was used. All data were gathered in a pharmaceutical datasheet, the theoretical DI were identified and real DI were detected by using hematologic tests and the patient’s clinical evolution. After the detection of any real DI, a pharmaceutical intervention took place. Results: A total of 106 DI were detected; 86% of DI found were related to drug’s pharmacokinetic properties, which were mostly metabolism related interactions (96.9%; the most commonly found associations were atazanavir with ritonavir, efavirenz with atorvastatin and efavirenz with gemfibrozil. The main clinical consequences associated with DI were ADR (49%. Conclusions: High prevalence of metabolism-related interactions was found and the antiretroviral drugs mostly associated with DI were found to be atazanavir, ritonavir y efavirenz. A high prevalence of ADR was found; however, they were mild or moderate.

  3. A Fully Automated High-Throughput Flow Cytometry Screening System Enabling Phenotypic Drug Discovery.

    Science.gov (United States)

    Joslin, John; Gilligan, James; Anderson, Paul; Garcia, Catherine; Sharif, Orzala; Hampton, Janice; Cohen, Steven; King, Miranda; Zhou, Bin; Jiang, Shumei; Trussell, Christopher; Dunn, Robert; Fathman, John W; Snead, Jennifer L; Boitano, Anthony E; Nguyen, Tommy; Conner, Michael; Cooke, Mike; Harris, Jennifer; Ainscow, Ed; Zhou, Yingyao; Shaw, Chris; Sipes, Dan; Mainquist, James; Lesley, Scott

    2018-05-01

    The goal of high-throughput screening is to enable screening of compound libraries in an automated manner to identify quality starting points for optimization. This often involves screening a large diversity of compounds in an assay that preserves a connection to the disease pathology. Phenotypic screening is a powerful tool for drug identification, in that assays can be run without prior understanding of the target and with primary cells that closely mimic the therapeutic setting. Advanced automation and high-content imaging have enabled many complex assays, but these are still relatively slow and low throughput. To address this limitation, we have developed an automated workflow that is dedicated to processing complex phenotypic assays for flow cytometry. The system can achieve a throughput of 50,000 wells per day, resulting in a fully automated platform that enables robust phenotypic drug discovery. Over the past 5 years, this screening system has been used for a variety of drug discovery programs, across many disease areas, with many molecules advancing quickly into preclinical development and into the clinic. This report will highlight a diversity of approaches that automated flow cytometry has enabled for phenotypic drug discovery.

  4. Orbitrap technology for comprehensive metabolite-based liquid chromatographic–high resolution-tandem mass spectrometric urine drug screening – Exemplified for cardiovascular drugs

    International Nuclear Information System (INIS)

    Helfer, Andreas G.; Michely, Julian A.; Weber, Armin A.; Meyer, Markus R.; Maurer, Hans H.

    2015-01-01

    LC–high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC–HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC–HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing. - Highlights: • First study on the application of Orbitrap technology for comprehensive drug screening in clinical and forensic toxicology. • Simple workup, sufficient separation, and powerful screening and identification using modern high resolution MS. • Validation of the assay according to guidelines for qualitative approaches. • Elucidation of the power of new data evaluation software in combination with a new reference drug and metabolite library. • Great relevance for science and practice in clinical and forensic

  5. Orbitrap technology for comprehensive metabolite-based liquid chromatographic–high resolution-tandem mass spectrometric urine drug screening – Exemplified for cardiovascular drugs

    Energy Technology Data Exchange (ETDEWEB)

    Helfer, Andreas G.; Michely, Julian A.; Weber, Armin A.; Meyer, Markus R.; Maurer, Hans H., E-mail: hans.maurer@uks.eu

    2015-09-03

    LC–high resolution (HR)-MS well established in proteomics has become more and more important in bioanalysis of small molecules over the last few years. Its high selectivity and specificity provide best prerequisites for its use in broad screening approaches. Therefore, Orbitrap technology was tested for developing a general metabolite-based LC–HR-MS/MS screening approach for urinalysis of drugs necessary in clinical and forensic toxicology. After simple urine precipitation, the drugs and their metabolites were separated within 10 min and detected by a Q-Exactive mass spectrometer in full scan with positive/negative switching, and subsequent data dependent acquisition (DDA) mode. Identification criteria were the presence of accurate precursor ions, isotopic patterns, five most intense fragment ions, and comparison with full HR-MS/MS library spectra. The current library contains over 1900 parent drugs and 1200 metabolites. The method was validated for typical drug representatives and metabolites concerning recovery, matrix effects, process efficiency, and limits showed acceptable results. The applicability was tested first for cardiovascular drugs, which should be screened for in poisoning cases and for medication adherence of hypertension patients. The novel LC–HR-MS/MS method allowed fast, simple, and robust urine screening, particularly for cardiovascular drugs showing the usefulness of Orbitrap technology for drug testing. - Highlights: • First study on the application of Orbitrap technology for comprehensive drug screening in clinical and forensic toxicology. • Simple workup, sufficient separation, and powerful screening and identification using modern high resolution MS. • Validation of the assay according to guidelines for qualitative approaches. • Elucidation of the power of new data evaluation software in combination with a new reference drug and metabolite library. • Great relevance for science and practice in clinical and forensic

  6. Effects of Community Based Educational Prevention Program of Drug Abuse in Reduction of High Risk Behavior

    Directory of Open Access Journals (Sweden)

    H Aranpour

    2010-08-01

    Full Text Available Introduction: Overcoming social problems requires a participatory approach. This study was performed in order to determine the effect of community based educational prevention program of drug abuse in reduction of high risk behavior. Methods: This study was a community based participatory research. According to planned approach to community health model, "the health companion group" was established with participation of public representatives of villages, researchers, and managers of health sectors. Need assessment and priority setting of health problems was done. Drug abuse was selected as the topmost priority of health problems. By interviewing 10 year olds and older members of households, the questionnaires were completed. By conducting workshops, distributing educational pamphlets and face to face training for six months, the educational program was carried out. After this period, the study population was interviewed again. Data was analyzed by SPSS software, X2, and T tests. Results: The mean score of drug abuse related high risk behavior was 26.8 +/- 2.05 before educational program and 25.2 ±2.3 after the program. The mean score of psychological health was 26.2±5.8 before educational program and 26.4±5.7 after the program. The rate of negative drug abusing related behavior decreased and positive behavior increased after the educational program. Conclusion: The community based participatory research with participation of the public can be a proper pattern to prevent drug abuse and related high risk behaviors and as a result reduce costs and complications of this problem.

  7. Vascular entrapment of the sciatic plexus causing catamenial sciatica and urinary symptoms.

    Science.gov (United States)

    Lemos, Nucelio; Marques, Renato Moretti; Kamergorodsky, Gil; Ploger, Christine; Schor, Eduardo; Girão, Manoel J B C

    2016-02-01

    Pelvic congestion syndrome is a well-known cause of cyclic pelvic pain (Ganeshan et al., Cardiovasc Intervent Radiol 30(6):1105-11, 2007). What is much less well known is that dilated or malformed branches of the internal or external iliac vessels can entrap the nerves of the sacral plexus against the pelvic sidewalls, producing symptoms that are not commonly seen in gynecological practice, such as sciatica, or refractory urinary and anorectal dysfunction (Possover et al., Fertil Steril 95(2):756-8. 2011). The objective of this video is to explain and describe the symptoms suggestive of vascular entrapment of the sacral plexus, as well as the technique for the laparoscopic decompression of these nerves. Two anecdotal cases of intrapelvic vascular entrapment are used to review the anatomy of the lumbosacral plexus and demonstrate the laparoscopic surgical technique for decompression at two different sites, one on the sciatic nerve and one on the sacral nerve roots. After surgery, the patient with the sciatic entrapment showed full recovery of the sciatica and partial recovery of the myofascial pain. The patient with sacral nerve root entrapment showed full recovery with resolution of symptoms. The symptoms suggestive of intrapelvic nerve entrapment are: perineal pain or pain irradiating to the lower limbs in the absence of a spinal disorder, and lower urinary tract symptoms in the absence of prolapse of a bladder lesion. In the presence of such symptoms, the radiologist should provide specific MRI sequences of the intrapelvic portion of the sacral plexus and a team and equipment to expose and decompress the sacral nerves should be prepared.

  8. Results from the hydrodynamic element of the 1994 entrapment zone study in Suisun Bay

    Science.gov (United States)

    Burau, J.R.; Gartner, J.W.; Stacey, M.

    1998-01-01

    The entrapment zo as long been considered an important region of the San Francisco estuary. It has been the subject of several previous studies, and its location has been suggested as an index of condition of the estuarine ecosystem.A close correlate of this location, X2 1, is now used as a management objective on the basis that X2 is correlated with the abundance or survival of several estuarine-dependent species. X2 is a crude tool to use for this purpose, but it can be refined only through improved understanding of the various mechanisms underlying these correlations. These mechanisms probably differ among species, but for species resident in and near the entrapment zone, the correlation with X2 may be due to variations in intenSity oftrapping mechanisms with pOSition of the entrapment zone. Therefore, it is worthwhile to investigate these trapping mechanisms, the nature of the entrapment zone as habitat, and the responses of the entrapment zone to changes in X2 or outflow from the Sacramento-San Joaquin Delta. Studies ofthe entrapment zone ofthe San Francisco estuary have been conducted in springs of 1994, 1995, and 1996. These studies have been funded by the Interagency Ecological Program and conducted by scientists from IEP member agencies, the Romberg Tiburon Center for Environmental Studies, Bodega Marine Laboratory, and the University of California at Santa Cruz. This report presents results from 1994, a low-flow year. Subsequent reports will describe results from 1995 and 1996 and highlight differences among years. This report is organized in chapters that comprise more-or-Iess independent papers, with an introductory chapter for the entire study. This Executive Summary presents highlights of the overall study plan and summarizes the major findings.

  9. Incidence of tendon entrapment and dislocation with calcaneus and pilon fractures on CT examination

    Energy Technology Data Exchange (ETDEWEB)

    Tresley, Jonathan [Jackson Memorial Hospital, Department of Diagnostic Radiology, Miami, FL (United States); University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); Subhawong, Ty K.; Singer, Adam D.; Clifford, Paul D. [Jackson Memorial Hospital, Department of Diagnostic Radiology, Miami, FL (United States)

    2016-07-15

    To examine the association between tibial pilon and calcaneal fracture classification and tendon entrapment or dislocation. After institutional review board approval, we retrospectively reviewed consecutive CT scans with calcaneal or pilon fractures from 5 years at a level 1 trauma center. We categorized calcaneal fractures according to the Sanders classification, and pilon fractures according to the Ruedi and Allgower and the Arbeitsgemeinschaft fuer Osteosynthesefragen-Orthopaedic Trauma Association (AO-OTA) classifications. Ankle tendons were assessed for dislocation or entrapment. Fisher's exact test was used for statistical analysis with significance at p < 0.05. A total of 312 fractures (91 pilon only, 193 calcaneal only, and 14 ankles with ipsilateral pilon and calcaneal fractures) were identified in 273 patients. Twenty-two pilon, 42 calcaneal, and nine combination fractures were associated with 99 occurrences of tendon entrapment or superior peroneal retinacular injury. Such findings were associated with multiple fractures (p = 0.002). Multifragmentary pilon fractures were associated with posterior tibial and flexor digitorum longus tendon entrapment (p < 0.0001 and p = 0.0003 for Ruedi/Allgower and AO-OTA, respectively), and multifragmentary Sanders type 3 or 4 calcaneal fractures were associated with superior peroneal retinacular injury (p = 0.0473) compared to simple fracture patterns. Thirty-nine percent of tendon entrapments or retinacular injuries were prospectively identified, 85 % by musculoskeletal radiologists (p < 0.0001). Approximately 25 % of calcaneal and pilon fractures were retrospectively identified to contain posteromedial tendon entrapment or superior peroneal retinacular injury. Radiologists should meticulously search for such injuries, particularly when analyzing multifragmentary and multiple fractures. (orig.)

  10. Incidence of tendon entrapment and dislocation with calcaneus and pilon fractures on CT examination

    International Nuclear Information System (INIS)

    Tresley, Jonathan; Subhawong, Ty K.; Singer, Adam D.; Clifford, Paul D.

    2016-01-01

    To examine the association between tibial pilon and calcaneal fracture classification and tendon entrapment or dislocation. After institutional review board approval, we retrospectively reviewed consecutive CT scans with calcaneal or pilon fractures from 5 years at a level 1 trauma center. We categorized calcaneal fractures according to the Sanders classification, and pilon fractures according to the Ruedi and Allgower and the Arbeitsgemeinschaft fuer Osteosynthesefragen-Orthopaedic Trauma Association (AO-OTA) classifications. Ankle tendons were assessed for dislocation or entrapment. Fisher's exact test was used for statistical analysis with significance at p < 0.05. A total of 312 fractures (91 pilon only, 193 calcaneal only, and 14 ankles with ipsilateral pilon and calcaneal fractures) were identified in 273 patients. Twenty-two pilon, 42 calcaneal, and nine combination fractures were associated with 99 occurrences of tendon entrapment or superior peroneal retinacular injury. Such findings were associated with multiple fractures (p = 0.002). Multifragmentary pilon fractures were associated with posterior tibial and flexor digitorum longus tendon entrapment (p < 0.0001 and p = 0.0003 for Ruedi/Allgower and AO-OTA, respectively), and multifragmentary Sanders type 3 or 4 calcaneal fractures were associated with superior peroneal retinacular injury (p = 0.0473) compared to simple fracture patterns. Thirty-nine percent of tendon entrapments or retinacular injuries were prospectively identified, 85 % by musculoskeletal radiologists (p < 0.0001). Approximately 25 % of calcaneal and pilon fractures were retrospectively identified to contain posteromedial tendon entrapment or superior peroneal retinacular injury. Radiologists should meticulously search for such injuries, particularly when analyzing multifragmentary and multiple fractures. (orig.)

  11. The distribution of radiolabelled drug in animals infected with cutaneous leishmaniasis: comparison of free and liposome-bound sodium stibogluconate

    International Nuclear Information System (INIS)

    New, R.R.C.; Chance, M.L.; Critchley, M.

    1982-01-01

    Sodium stibogluconate, labelled with antimony 125, was used to study the altered distribution of drugs, entrapped by positively and negatively charged liposomes, used to treat cutaneous leishmaniasis. (U.K.)

  12. Stump entrapment of the anterior cruciate ligament in late childhood and adolescence

    Energy Technology Data Exchange (ETDEWEB)

    Meyers, Arthur B.; Laor, Tal; Zbojniewicz, Andrew M. [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States)

    2011-08-15

    Displacement of a portion of the torn anterior cruciate ligament (ACL) into the intercondylar notch can cause a focal fibrotic reaction similar to that seen following ACL reconstruction. This displacement, which can result in locking or limitation of knee extension, is termed stump entrapment and is described in adult MR imaging literature. We present a pictorial essay of the etiology and appearance of stump entrapment on MR imaging of the knee in an older child and adolescents and review the significance of this finding. (orig.)

  13. Entrapment of the acetabular labrum following reduction of traumatic hip dislocation in a child

    Energy Technology Data Exchange (ETDEWEB)

    Chun, K.A. [The Catholic University of Korea Uijongbu St. Mary' s Hospital, Department of Radiology, Uijongbu, Kyunggi-Do 480-130 (Korea); University of Iowa Hospitals and Clinics, Department of Radiology, Iowa City (United States); Morcuende, J. [University of Iowa Hospitals and Clinics, Department of Orthopaedic Surgery, Iowa City (United States); El-Khoury, G.Y. [University of Iowa Hospitals and Clinics, Department of Radiology, Iowa City (United States)

    2004-12-01

    In traumatic hip dislocation, concentric reduction can be prevented by various causes. Soft-tissue interposition, such as entrapment of the acetabular labrum, is a rare but important cause of failed reduction of a hip. Early diagnosis of incomplete reduction due to interposition of soft tissue is important, because delayed treatment is associated with a greater incidence of avascular necrosis of the femoral head and early onset of osteoarthritis. This report describes a case of acetabular labral entrapment following reduction of traumatic hip dislocation in a child. The importance of CT and MRI in arriving at an early diagnosis is emphasized. (orig.)

  14. Atypical presentation of popliteal artery entrapment syndrome: involvement of the anterior tibial artery.

    Science.gov (United States)

    Bou, Steven; Day, Carly

    2014-11-01

    Popliteal artery entrapment syndrome (PAES) is a rare condition that should be suspected in a young patient with exertional lower extremity pain. We report the case of an 18-year-old female volleyball player with bilateral exertional lower extremity pain who had been previously diagnosed with tendinitis and periostitis. Diagnostic studies showed entrapment of the left popliteal artery and the left anterior tibial artery. To our knowledge, there has only been 1 previous report of anterior tibial artery involvement in PAES. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  15. Extrinsic mechanism obstructing the opening of a prosthetic mitral valve: an unusual case of suture entrapment.

    Science.gov (United States)

    Ozkan, Mehmet; Astarcioglu, Mehmet Ali; Karakoyun, Suleyman; Balkanay, Mehmet

    2012-02-01

    Obstruction to a prosthetic cardiac valve is a well-recognized complication of cardiac valve replacement. Malfunction of the mobile component of a prosthetic valve to open or close correctly may occur in consequence of intrinsic or extrinsic causes (thrombus, vegetation, entrapment of left ventricular myocardium, suture entanglement, and pannus formation) that may result prosthetic valve stenosis and/or insufficiency. In the case we report a 48-year-old female with valve dysfunction occurred early after surgery, as one valve leaflet was only able to partially open due to suture entrapment. © 2011, Wiley Periodicals, Inc.

  16. Entrapment of the acetabular labrum following reduction of traumatic hip dislocation in a child

    International Nuclear Information System (INIS)

    Chun, K.A.; Morcuende, J.; El-Khoury, G.Y.

    2004-01-01

    In traumatic hip dislocation, concentric reduction can be prevented by various causes. Soft-tissue interposition, such as entrapment of the acetabular labrum, is a rare but important cause of failed reduction of a hip. Early diagnosis of incomplete reduction due to interposition of soft tissue is important, because delayed treatment is associated with a greater incidence of avascular necrosis of the femoral head and early onset of osteoarthritis. This report describes a case of acetabular labral entrapment following reduction of traumatic hip dislocation in a child. The importance of CT and MRI in arriving at an early diagnosis is emphasized. (orig.)

  17. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

    Directory of Open Access Journals (Sweden)

    Kanika Madaan

    2014-01-01

    Full Text Available Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity.

  18. Dendrimers in drug delivery and targeting: Drug-dendrimer interactions and toxicity issues

    Science.gov (United States)

    Madaan, Kanika; Kumar, Sandeep; Poonia, Neelam; Lather, Viney; Pandita, Deepti

    2014-01-01

    Dendrimers are the emerging polymeric architectures that are known for their defined structures, versatility in drug delivery and high functionality whose properties resemble with biomolecules. These nanostructured macromolecules have shown their potential abilities in entrapping and/or conjugating the high molecular weight hydrophilic/hydrophobic entities by host-guest interactions and covalent bonding (prodrug approach) respectively. Moreover, high ratio of surface groups to molecular volume has made them a promising synthetic vector for gene delivery. Owing to these properties dendrimers have fascinated the researchers in the development of new drug carriers and they have been implicated in many therapeutic and biomedical applications. Despite of their extensive applications, their use in biological systems is limited due to toxicity issues associated with them. Considering this, the present review has focused on the different strategies of their synthesis, drug delivery and targeting, gene delivery and other biomedical applications, interactions involved in formation of drug-dendrimer complex along with characterization techniques employed for their evaluation, toxicity problems and associated approaches to alleviate their inherent toxicity. PMID:25035633

  19. Design and Development of a Proniosomal Transdermal Drug ...

    African Journals Online (AJOL)

    Purpose: The aim of the study was to develop a proniosomal carrier system for captopril for the treatment of hypertension that is capable of efficiently delivering entrapped drug over an extended period of time. Method: The potential of proniosomes as a transdermal drug delivery system for captopril was investigated by ...

  20. Risk Factors of Narcotic and Psychoactive Drugs Use among University and High School Student

    Directory of Open Access Journals (Sweden)

    Ali Kashi

    2010-05-01

    Full Text Available Aim: Today use of different banned substances such as narcotic, psychoactive and energetic drugs are social problem that has created worry in different levels of human societies. The aim of present study was examined the prevalence of use of narcotic and psychoactive drugs among high school and university students also identifying of risk factors associated with the use of this materials. Method: The population of this descriptive survey study was all students of high school and university of Khodabandeh city. By cluster random sampling 580 students of high school and university selected and questionnaires distributed among them. After eliminating incomplete questionnaires 480 students remained as research sample. Results: In consideration of selected sample the most important reasons of using of narcotics are: enjoying and curiosity, exposed to bad environment like addicted friends and families, joblessness, economic problems, lack of information and loss of affection. Conclusion: The analysis of the results indicated the high prevalence of narcotic and drugs use and necessity of codification of preventive programs for these people.

  1. Drug-to-antibody determination for an antibody-drug-conjugate utilizing cathepsin B digestion coupled with reversed-phase high-pressure liquid chromatography analysis.

    Science.gov (United States)

    Adamo, Michael; Sun, Guoyong; Qiu, Difei; Valente, Joseph; Lan, Wenkui; Song, Hangtian; Bolgar, Mark; Katiyar, Amit; Krishnamurthy, Girija

    2017-01-20

    Antibody drug conjugates or ADCs are currently being evaluated for their effectiveness as targeted chemotherapeutic agents across the pharmaceutical industry. Due to the complexity arising from the choice of antibody, drug and linker; analytical methods for release and stability testing are required to provide a detailed understanding of both the antibody and the drug during manufacturing and storage. The ADC analyzed in this work consists of a tubulysin drug analogue that is randomly conjugated to lysine residues in a human IgG1 antibody. The drug is attached to the lysine residue through a peptidic, hydrolytically stable, cathepsin B cleavable linker. The random lysine conjugation produces a heterogeneous mixture of conjugated species with a variable drug-to-antibody ratio (DAR), therefore, the average amount of drug attached to the antibody is a critical parameter that needs to be monitored. In this work we have developed a universal method for determining DAR in ADCs that employ a cathepsin B cleavable linker. The ADC is first cleaved at the hinge region and then mildly reduced prior to treatment with the cathepsin B enzyme to release the drug from the antibody fragments. This pre-treatment allows the cathepsin B enzyme unrestricted access to the cleavage sites and ensures optimal conditions for the cathepsin B to cleave all the drug from the ADC molecule. The cleaved drug is then separated from the protein components by reversed phase high performance liquid chromatography (RP-HPLC) and quantitated using UV absorbance. This method affords superior cleavage efficiency to other methods that only employ a cathepsin digestion step as confirmed by mass spectrometry analysis. This method was shown to be accurate and precise for the quantitation of the DAR for two different random lysine conjugated ADC molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Misuse of prescription and illicit drugs among high-risk young adults in Los Angeles and New York

    Directory of Open Access Journals (Sweden)

    Stephen E. Lankenau

    2012-02-01

    Full Text Available Background. Prescription drug misuse among young adults is increasingly viewed as a public health concern, yet most research has focused on student populations and excluded high-risk groups. Furthermore, research on populations who report recent prescription drug misuse is limited. This study examined patterns of prescription drug misuse among high-risk young adults in Los Angeles (LA and New York (NY, which represent different local markets for illicit and prescription drugs. Design and Methods. Between 2009 and 2011, 596 young adults (16 to 25 years old who had misused prescription drugs within the past 90 days were interviewed in Los Angeles and New York. Sampling was stratified to enroll three groups of high-risk young adults: injection drug users (IDUs; homeless persons; and polydrug users. Results. In both sites, lifetime history of receiving a prescription for an opioid, tranquilizer, or stimulant was high and commonly preceded misuse. Moreover, initiation of opioids occurred before heroin and initiation of prescription stimulants happened prior to illicit stimulants. NY participants more frequently misused oxycodone, heroin, and cocaine, and LA participants more frequently misused codeine, marijuana, and methamphetamine. Combining prescription and illicit drugs during drug using events was commonly reported in both sites. Opioids and tranquilizers were used as substitutes for other drugs, e.g., heroin, when these drugs were not available. Conclusion. Patterns of drug use among high-risk young adults in Los Angeles and New York appear to be linked to differences in local markets in each city for illicit drugs and diverted prescription drugs.

  3. Enantioselective analysis of drugs: contributions of high-performance liquid chromatography and capillary electrophoresis

    OpenAIRE

    Bonato, Pierina Sueli; Jabor, Valquíria Aparecida Polisel; Gaitani, Cristiane Masetto de

    2005-01-01

    The demand for analytical methods suitable for accurate and reproducible determination of drug enantiomers has increased significantly in the last years. High-performance liquid chromatography (HPLC) using chiral stationary phases and capillary electrophoresis (CE) are the most important techniques used for this purpose. In this paper, the fundamental aspects of chiral separations using both techniques are presented. Some important aspects for the development of enantioselective methods, part...

  4. High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array.

    Science.gov (United States)

    Tung, Yi-Chung; Hsiao, Amy Y; Allen, Steven G; Torisawa, Yu-suke; Ho, Mitchell; Takayama, Shuichi

    2011-02-07

    Culture of cells as three-dimensional (3D) aggregates can enhance in vitro tests for basic biological research as well as for therapeutics development. Such 3D culture models, however, are often more complicated, cumbersome, and expensive than two-dimensional (2D) cultures. This paper describes a 384-well format hanging drop culture plate that makes spheroid formation, culture, and subsequent drug testing on the obtained 3D cellular constructs as straightforward to perform and adapt to existing high-throughput screening (HTS) instruments as conventional 2D cultures. Using this platform, we show that drugs with different modes of action produce distinct responses in the physiological 3D cell spheroids compared to conventional 2D cell monolayers. Specifically, the anticancer drug 5-fluorouracil (5-FU) has higher anti-proliferative effects on 2D cultures whereas the hypoxia activated drug commonly referred to as tirapazamine (TPZ) are more effective against 3D cultures. The multiplexed 3D hanging drop culture and testing plate provides an efficient way to obtain biological insights that are often lost in 2D platforms.

  5. Drug-induced lung disease: High-resolution CT and histological findings

    International Nuclear Information System (INIS)

    Cleverley, Joanne R.; Screaton, Nicholas J.; Hiorns, Melanie P.; Flint, Julia D.A.; Mueller, Nestor L.

    2002-01-01

    AIM: To compare the parenchymal high-resolution computed tomography (HRCT) appearances with histological findings in patients with drug-induced lung disease and to determine the prognostic value of HRCT. MATERIALS AND METHODS: Drug history, HRCT features, histological findings and outcome at 3 months in 20 patients with drug induced-lung disease were reviewed retrospectively. The HRCT images were assessed for the pattern and distribution of abnormalities and classified as most suggestive of interstitial pneumonitis/fibrosis, diffuse alveolar damage (DAD), organizing pneumonia (OP) reaction, or a hypersensitivity reaction. RESULTS: On histopathological examination there were eight cases of interstitial pneumonitis/fibrosis, five of DAD, five of OP reactions, one of hypersensitivity reaction and one of pulmonary eosinophilia. The most common abnormalities on HRCT were ground-glass opacities (n = 17), consolidation (n = 14), interlobular septal thickening (n = 15) and centrilobular nodules (n 8). HRCT interpretation and histological diagnosis were concordant in only nine (45%) of 20 patients. The pattern, distribution, and extent of HRCT abnormalities were of limited prognostic value: all eight patients with histological findings of OP, hypersensitivity reaction, or eosinophilic infiltrate improved on follow-up compared to only five of 13 patients with interstitial pneumonitis/fibrosis or DAD. CONCLUSION: In many cases of drug-induced lung injury HRCT is of limited value in determining the histological pattern and prognosis. Cleverly, J.R. et al

  6. Identifying and quantifying heterogeneity in high content analysis: application of heterogeneity indices to drug discovery.

    Directory of Open Access Journals (Sweden)

    Albert H Gough

    Full Text Available One of the greatest challenges in biomedical research, drug discovery and diagnostics is understanding how seemingly identical cells can respond differently to perturbagens including drugs for disease treatment. Although heterogeneity has become an accepted characteristic of a population of cells, in drug discovery it is not routinely evaluated or reported. The standard practice for cell-based, high content assays has been to assume a normal distribution and to report a well-to-well average value with a standard deviation. To address this important issue we sought to define a method that could be readily implemented to identify, quantify and characterize heterogeneity in cellular and small organism assays to guide decisions during drug discovery and experimental cell/tissue profiling. Our study revealed that heterogeneity can be effectively identified and quantified with three indices that indicate diversity, non-normality and percent outliers. The indices were evaluated using the induction and inhibition of STAT3 activation in five cell lines where the systems response including sample preparation and instrument performance were well characterized and controlled. These heterogeneity indices provide a standardized method that can easily be integrated into small and large scale screening or profiling projects to guide interpretation of the biology, as well as the development of therapeutics and diagnostics. Understanding the heterogeneity in the response to perturbagens will become a critical factor in designing strategies for the development of therapeutics including targeted polypharmacology.

  7. Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

    Directory of Open Access Journals (Sweden)

    Martina Nardoni

    2018-03-01

    Full Text Available Recently, magnetic nanoparticles (MNPs have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF, which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs, they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

  8. Can Pulsed Electromagnetic Fields Trigger On-Demand Drug Release from High-Tm Magnetoliposomes?

    Science.gov (United States)

    Nardoni, Martina; Della Valle, Elena; Liberti, Micaela; Relucenti, Michela; Casadei, Maria Antonietta; Paolicelli, Patrizia; Apollonio, Francesca; Petralito, Stefania

    2018-03-27

    Recently, magnetic nanoparticles (MNPs) have been used to trigger drug release from magnetoliposomes through a magneto-nanomechanical approach, where the mechanical actuation of the MNPs is used to enhance the membrane permeability. This result can be effectively achieved with low intensity non-thermal alternating magnetic field (AMF), which, however, found rare clinic application. Therefore, a different modality of generating non-thermal magnetic fields has now been investigated. Specifically, the ability of the intermittent signals generated by non-thermal pulsed electromagnetic fields (PEMFS) were used to verify if, once applied to high-transition temperature magnetoliposomes (high-Tm MLs), they could be able to efficiently trigger the release of a hydrophilic model drug. To this end, hydrophilic MNPs were combined with hydrogenated soybean phosphatidylcholine and cholesterol to design high-Tm MLs. The release of a dye was evaluated under the effect of PEMFs for different times. The MNPs motions produced by PEMF could effectively increase the bilayer permeability, without affecting the liposomes integrity and resulted in nearly 20% of release after 3 h exposure. Therefore, the current contribution provides an exciting proof-of-concept for the ability of PEMFS to trigger drug release, considering that PEMFS find already application in therapy due to their anti-inflammatory effects.

  9. Highly stable, protein capped gold nanoparticles as effective drug delivery vehicles for amino-glycosidic antibiotics

    International Nuclear Information System (INIS)

    Rastogi, Lori; Kora, Aruna Jyothi; Arunachalam, J.

    2012-01-01

    A method for the production of highly stable gold nanoparticles (Au NP) was optimized using sodium borohydride as reducing agent and bovine serum albumin as capping agent. The synthesized nanoparticles were characterized using UV–visible spectroscopy, transmission electron microscopy, X‐ray diffraction (XRD) and dynamic light scattering techniques. The formation of gold nanoparticles was confirmed from the appearance of pink colour and an absorption maximum at 532 nm. These protein capped nanoparticles exhibited excellent stability towards pH modification and electrolyte addition. The produced nanoparticles were found to be spherical in shape, nearly monodispersed and with an average particle size of 7.8 ± 1.7 nm. Crystalline nature of the nanoparticles in face centered cubic structure is confirmed from the selected‐area electron diffraction and XRD patterns. The nanoparticles were functionalized with various amino-glycosidic antibiotics for utilizing them as drug delivery vehicles. Using Fourier transform infrared spectroscopy, the possible functional groups of antibiotics bound to the nanoparticle surface have been examined. These drug loaded nanoparticle solutions were tested for their antibacterial activity against Gram-negative and Gram-positive bacterial strains, by well diffusion assay. The antibiotic conjugated Au NP exhibited enhanced antibacterial activity, compared to pure antibiotic at the same concentration. Being protein capped and highly stable, these gold nanoparticles can act as effective carriers for drugs and might have considerable applications in the field of infection prevention and therapeutics. - Highlights: ► Method for NaBH 4 reduced and BSA capped gold nanoparticle was standardized. ► Nanoparticles were spherical and nearly monodispersed with a size of 7.8 nm. ► Nanoparticles are extremely stable towards pH modification and electrolyte addition. ► Antibiotic conjugated nanoparticles exhibited enhanced antibacterial activity

  10. Nanoparticles with entrapped {alpha}-tocopherol: synthesis, characterization, and controlled release

    Energy Technology Data Exchange (ETDEWEB)

    Zigoneanu, Imola Gabriela [101 E B Doran Building, BAE Department, Louisiana State University Agricultural Center, Baton Rouge, LA 70803 (United States); Astete, Carlos Ernesto [110 E B Doran Building, BAE Department, Louisiana State University Agricultural Center, Baton Rouge, LA 70803 (United States); Sabliov, Cristina Mirela [141 E B Doran Building, BAE Department, Louisiana State University Agricultural Center, Baton Rouge, LA 70803 (United States)], E-mail: csabliov@lsu.edu

    2008-03-12

    An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped {alpha}-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of {alpha}-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of {alpha}-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% {alpha}-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the {alpha}-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% {alpha}-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% {alpha}-tocopherol theoretical loading (34% released in the first hour)

  11. Nanoparticles with entrapped α-tocopherol: synthesis, characterization, and controlled release

    International Nuclear Information System (INIS)

    Zigoneanu, Imola Gabriela; Astete, Carlos Ernesto; Sabliov, Cristina Mirela

    2008-01-01

    An emulsion evaporation method was used to synthesize spherical poly(DL-lactide-co-glycolide) (PLGA) nanoparticles with entrapped α-tocopherol. Two different surfactants were used: sodium dodecyl sulfate (SDS) and poly(vinyl alcohol) (PVA). For SDS nanoparticles, the size of the nanoparticles decreased significantly with the entrapment of α-tocopherol in the PLGA matrix, while the size of PVA nanoparticles remained unchanged. The polydispersity index after synthesis was under 0.100 for PVA nanoparticles and around 0.150 for SDS nanoparticles. The zeta potential was negative for all PVA nanoparticles. The entrapment efficiency of α-tocopherol in the polymeric matrix was approximately 89% and 95% for nanoparticles with 8% and 16% α-tocopherol theoretical loading, respectively. The residual PVA associated with the nanoparticles after purification was approximately 6% ( w/w relative to the nanoparticles). The release profile showed an initial burst followed by a slower release of the α-tocopherol entrapped inside the PLGA matrix. The release for nanoparticles with 8% α-tocopherol theoretical loading (86% released in the first hour) was faster than the release for the nanoparticles with 16% α-tocopherol theoretical loading (34% released in the first hour)

  12. Entrapped air bubbles in piezo-driven inkjet printing: their effect on the droplet velocity

    NARCIS (Netherlands)

    Jong, de J.; Jeurissen, R.J.M.; Borel, H.; Berg, van den M.; Versluis, M.; Wijshoff, H.M.A.; Prosperetti, A.; Reinten, H.; Lohse, D.

    2006-01-01

    Air bubbles entrapped in the ink channel are a major problem in piezo-driven inkjet printing. They grow by rectified diffusion and eventually counteract the pressure buildup at the nozzle, leading to a breakdown of the jetting process. Experimental results on the droplet velocity udrop as a function

  13. Entrapped air bubbles in piezo-driven inkjet printing: Their effect on the droplet velocity

    NARCIS (Netherlands)

    de Jong, J.; Jeurissen, R.J.M.; Borel, Huub; van den Berg, Marc; Wijshoff, Herman; Versluis, Michel; Wijshoff, H.; Reinten, Hans; Prosperetti, Andrea; Lohse, Detlef

    2006-01-01

    Air bubbles entrapped in the ink channel are a major problem in piezo-driven inkjet printing. They grow by rectified diffusion and eventually counteract the pressure buildup at the nozzle, leading to a breakdown of the jetting process. Experimental results on the droplet velocity udrop as a function

  14. Side-branch wire entrapment during bifurcation PCI: avoidance and management.

    Science.gov (United States)

    Burns, Andrew T; Gutman, Jack; Whitbourn, Rob

    2010-02-15

    An LAD/D1 bifurcation intervention was complicated by side-branch wire entrapment and unravelling requiring goose-neck snare removal. Residual microfilaments were retrieved from the main branch after further balloon inflations with a satisfactory final angiographic result and one-year follow-up. Various methods are available to avoid and deal with this complication.

  15. Defeat and entrapment as predictors of depression and suicidal ideation versus hopelessness and helplessness.

    Science.gov (United States)

    Lester, David

    2012-10-01

    In a sample of 140 undergraduate students, measures of defeat and entrapment and of haplessness, helplessness, and hopelessness were similar in their ability to predict depression and suicidality. It was concluded that the two sets of measures may tap the same cognitive mind set.

  16. The Role of Defeat and Entrapment in Depression, Anxiety, and Suicide

    Science.gov (United States)

    Taylor, Peter James; Gooding, Patricia; Wood, Alex M.; Tarrier, Nicholas

    2011-01-01

    Defeat and entrapment are psychological constructs that have played a central role in evolutionary accounts of depression. These concepts have since been implicated in theoretical accounts of anxiety disorders and suicidality. The current article reports on a systematic review of the existing research investigating the links among defeat,…

  17. Ethanol production potential from fermented rice noodle wastewater treatment using entrapped yeast cell sequencing batch reactor

    Science.gov (United States)

    Siripattanakul-Ratpukdi, Sumana

    2012-03-01

    Fermented rice noodle production generates a large volume of starch-based wastewater. This study investigated the treatment of the fermented rice noodle wastewater using entrapped cell sequencing batch reactor (ECSBR) compared to traditional sequencing batch reactor (SBR). The yeast cells were applied because of their potential to convert reducing sugar in the wastewater to ethanol. In present study, preliminary treatment by acid hydrolysis was performed. A yeast culture, Saccharomyces cerevisiae, with calcium alginate cell entrapment was used. Optimum yeast cell loading in batch experiment and fermented rice noodle treatment performances using ECSBR and SBR systems were examined. In the first part, it was found that the cell loadings (0.6-2.7 × 108 cells/mL) did not play an important role in this study. Treatment reactions followed the second-order kinetics with the treatment efficiencies of 92-95%. In the second part, the result showed that ECSBR performed better than SBR in both treatment efficiency and system stability perspectives. ECSBR maintained glucose removal of 82.5 ± 10% for 5-cycle treatment while glucose removal by SBR declined from 96 to 40% within the 5-cycle treatment. Scanning electron microscopic images supported the treatment results. A number of yeast cells entrapped and attached onto the matrix grew in the entrapment matrix.

  18. Prospective Predictors of Suicidality: Defeat and Entrapment Lead to Changes in Suicidal Ideation over Time

    Science.gov (United States)

    Taylor, Peter James; Gooding, Patricia A.; Wood, Alex M.; Johnson, Judith; Tarrier, Nicholas

    2011-01-01

    Theoretical perspectives into suicidality have suggested that heightened perceptions of defeat and entrapment lead to suicidality. However, all previous empirical work has been cross-sectional. We provide the first longitudinal test of the theoretical predictions, in a sample of 79 students who reported suicidality. Participants completed…

  19. Subcutaneous administration of carrier erythrocytes: slow release of entrapped agent

    International Nuclear Information System (INIS)

    DeLoach, J.R.; Corrier, D.E.

    1988-01-01

    Carrier erythrocytes administered subcutaneously in mice release encapsulated molecules at the injection site and through cells that escape the injection site. One day postinjection, the efflux of encapsulated [ 14 C]sucrose, [ 3 H]inulin, and 51 Cr-hemoglobin from the injection site was 45, 55, and 65%, respectively. Intact carrier erythrocytes escaped the injection site and entered the blood circulation carrying with them the encapsulated molecules. Most of the encapsulated [ 3 H]inulin that reached whole blood circulated within erythrocytes. Small but measurable numbers of encapsulated molecules were trapped within lymph nodes. Subcutaneous injection of carrier erythrocytes may allow for limited extravascular tissue targeting of drugs

  20. Improving co-amorphous drug formulations by the addition of the highly water soluble amino acid proline

    DEFF Research Database (Denmark)

    Jensen, Katrine Birgitte Tarp; Löbmann, Korbinian; Rades, Thomas

    2014-01-01

    Co-amorphous drug amino acid mixtures were previously shown to be a promising approach to create physically stable amorphous systems with the improved dissolution properties of poorly water-soluble drugs. The aim of this work was to expand the co-amorphous drug amino acid mixture approach...... by combining the model drug, naproxen (NAP), with an amino acid to physically stabilize the co-amorphous system (tryptophan, TRP, or arginine, ARG) and a second highly soluble amino acid (proline, PRO) for an additional improvement of the dissolution rate. Co-amorphous drug-amino acid blends were prepared...... the molecular interactions in the form of hydrogen bonds between all three components in the mixture. A salt formation between the acidic drug, NAP, and the basic amino acid, ARG, was found in co-amorphous NAP–ARG. In comparison to crystalline NAP, binary NAP–TRP and NAP–ARG, it could be shown that the highly...

  1. Labile conjugation of a hydrophilic drug to PLA oligomers to modify a drug delivery system: cephradin in a PLAGA matrix.

    Science.gov (United States)

    Ustariz-Peyret, C; Coudane, J; Vert, M; Kaltsatos, V; Boisramené, B

    2000-01-01

    The physical entrapment of a hydrophilic drug within degradable microspheres is generally difficult because of poor entrapment yield and/or fast release, depending on the microsphere fabrication method. In order to counter the effects of drug hydrophilicity, it is proposed to covalently attach the drug to lactic acid oligomers, with the aim of achieving temporary hydrophobization and slower release controlled by the separation of the drug from the degradable link within the polymer matrix. This strategy was tested on microspheres of the antibiotic cephradin. As the prodrug form, the entrapment of the drug was almost quantitative. The prodrug did degrade in an aqueous medium, modelling body fluids, but cleavage did not occur at the drug-oligomer junction and drug molecules bearing two lactyl residual units were released. When the prodrug is entrapped within a PLAGA matrix, no release was observed within the experimental time period. However, data suggest that conjugation via a bond more sensitive to hydrolysis than the main chain PLA ester bonds should make the system work as desired.

  2. Structure and dynamics of spin-labeled insulin entrapped in a silica matrix by the sol-gel method.

    Science.gov (United States)

    Vanea, E; Gruian, C; Rickert, C; Steinhoff, H-J; Simon, V

    2013-08-12

    The structure and conformational dynamics of insulin entrapped into a silica matrix was monitored during the sol to maturated-gel transition by electron paramagnetic resonance (EPR) spectroscopy. Insulin was successfully spin-labeled with iodoacetamide and the bifunctional nitroxide reagent HO-1944. Room temperature continuous wave (cw) EPR spectra of insulin were recorded to assess the mobility of the attached spin labels. Insulin conformation and its distribution within the silica matrix were studied using double electron-electron resonance (DEER) and low-temperature cw-EPR. A porous oxide matrix seems to form around insulin molecules with pore diameters in the order of a few nanometers. Secondary structure of the encapsulated insulin investigated by Fourier transform infrared spectroscopy proved a high structural integrity of insulin even in the dried silica matrix. The results show that silica encapsulation can be used as a powerful tool to effectively isolate and functionally preserve biomolecules during preparation, storage, and release.

  3. Inquiry-based Laboratory Activities on Drugs Analysis for High School Chemistry Learning

    Science.gov (United States)

    Rahmawati, I.; Sholichin, H.; Arifin, M.

    2017-09-01

    Laboratory activity is an important part of chemistry learning, but cookbook instructions is still commonly used. However, the activity with that way do not improve students thinking skill, especially students creativity. This study aims to improve high school students creativity through inquiry-based laboratory on drugs analysis activity. Acid-base titration is used to be method for drugs analysis involving a color changing indicator. The following tools were used to assess the activity achievement: creative thinking test on acid base titration, creative attitude and action observation sheets, questionnaire of inquiry-based lab activities, and interviews. The results showed that the inquiry-based laboratory activity improving students creative thinking, creative attitude and creative action. The students reacted positively to this teaching strategy as demonstrated by results from questionnaire responses and interviews. This result is expected to help teachers to overcome the shortcomings in other laboratory learning.

  4. Exploiting the high-affinity phosphonate-hydroxyapatite nanoparticle interaction for delivery of radiation and drugs

    International Nuclear Information System (INIS)

    Ong, Hooi Tin; Loo, Joachim S. C.; Boey, Freddy Y. C.; Russell, Stephen J.; Ma Jan; Peng, Kah-Whye

    2008-01-01

    Hydroxyapatite is biocompatible and used in various biomedical applications. Here, we generated hydroxyapatite nanoparticles (HNPs) of various sizes (40-200 nm) and demonstrated that they can be stably loaded with drugs or radioisotopes by exploiting the high-affinity HA-(poly)phosphonate interaction. Clinically available phosphonates, clodronate, and Tc-99m-methylene-diphosphonate (Tc-99m-MDP), were efficiently loaded onto HNPs within 15 min. Biodistribution of radiolabeled HNP-MDP-Tc99m in mice was monitored non-invasively using microSPECT-CT. Imaging and dosimetry studies indicated that the HNPs, regardless of size, were quickly taken up by Kupffer cells in the liver after systemic administration into mice. Clodronate loaded onto HNPs remained biologically active and were able to result in selective depletion of Kupffer cells. This method of drug or isotope loading on HA is fast and easy as it eliminates the need for additional surface modifications of the nanoparticles

  5. A high content, high throughput cellular thermal stability assay for measuring drug-target engagement in living cells.

    Science.gov (United States)

    Massey, Andrew J

    2018-01-01

    Determining and understanding drug target engagement is critical for drug discovery. This can be challenging within living cells as selective readouts are often unavailable. Here we describe a novel method for measuring target engagement in living cells based on the principle of altered protein thermal stabilization / destabilization in response to ligand binding. This assay (HCIF-CETSA) utilizes high content, high throughput single cell immunofluorescent detection to determine target protein levels following heating of adherent cells in a 96 well plate format. We have used target engagement of Chk1 by potent small molecule inhibitors to validate the assay. Target engagement measured by this method was subsequently compared to target engagement measured by two alternative methods (autophosphorylation and CETSA). The HCIF-CETSA method appeared robust and a good correlation in target engagement measured by this method and CETSA for the selective Chk1 inhibitor V158411 was observed. However, these EC50 values were 23- and 12-fold greater than the autophosphorylation IC50. The described method is therefore a valuable advance in the CETSA method allowing the high throughput determination of target engagement in adherent cells.

  6. Prospective associations of social self-control with drug use among youth from regular and alternative high schools

    Directory of Open Access Journals (Sweden)

    Sun Ping

    2007-07-01

    Full Text Available Abstract Background This study examined the one year prospective associations between adolescent social self-control and drug outcomes (cigarette use, alcohol use, marijuana use, hard drug use, and problem drug use among adolescents from regular and continuation high schools. In our previous cross-sectional study, poor social self-control was found to be associated with higher drug use, controlling for 12 personality disorder categories. In this study, we attempted to find out (a whether lack of social self-control predicted drug use one year later, and (b whether drug use at baseline predicted social self-control one year later. Methods We surveyed 2081 older adolescents from 9 regular (N = 1529 and 9 continuation (alternative (N = 552 high schools in the Los Angeles area. Data were collected at two time points in an interval of approximately 1 year. Results Past 30-day cigarette smoking, marijuana use, hard drug use, and problem drug use at baseline were found to predict lower social self-control at follow-up, controlling for baseline social self-control and demographic variables. The effect of problem drug use as a one-year predictor of social self-control was found to be moderated by school type (regular or continuation high school, such that the relationship was significant for continuation high school students only. Conversely, social self-control was found to predict past 30-day alcohol use, marijuana use, and problem drug use, controlling for baseline drug use and demographic variables. For alcohol use, marijuana use, and problem drug use outcomes, school type was not found to moderate the effects of social self-control, though an interaction effect was found regarding cigarette smoking. Social self-control was a significant predictor of cigarette use only at regular high school. Conclusion The results indicate that social self-control and drug use share a reciprocal relationship. Lack of social self-control in adolescents seems to

  7. Comparison of high-resolution ultrasonic resonator technology and Raman spectroscopy as novel process analytical tools for drug quantification in self-emulsifying drug delivery systems.

    Science.gov (United States)

    Stillhart, Cordula; Kuentz, Martin

    2012-02-05

    Self-emulsifying drug delivery systems (SEDDS) are complex mixtures in which drug quantification can become a challenging task. Thus, a general need exists for novel analytical methods and a particular interest lies in techniques with the potential for process monitoring. This article compares Raman spectroscopy with high-resolution ultrasonic resonator technology (URT) for drug quantification in SEDDS. The model drugs fenofibrate, indomethacin, and probucol were quantitatively assayed in different self-emulsifying formulations. We measured ultrasound velocity and attenuation in the bulk formulation containing drug at different concentrations. The formulations were also studied by Raman spectroscopy. We used both, an in-line immersion probe for the bulk formulation and a multi-fiber sensor for measuring through hard-gelatin capsules that were filled with SEDDS. Each method was assessed by calculating the relative standard error of prediction (RSEP) as well as the limit of quantification (LOQ) and the mean recovery. Raman spectroscopy led to excellent calibration models for the bulk formulation as well as the capsules. The RSEP depended on the SEDDS type with values of 1.5-3.8%, while LOQ was between 0.04 and 0.35% (w/w) for drug quantification in the bulk. Similarly, the analysis of the capsules led to RSEP of 1.9-6.5% and LOQ of 0.01-0.41% (w/w). On the other hand, ultrasound attenuation resulted in RSEP of 2.3-4.4% and LOQ of 0.1-0.6% (w/w). Moreover, ultrasound velocity provided an interesting analytical response in cases where the drug strongly affected the density or compressibility of the SEDDS. We conclude that ultrasonic resonator technology and Raman spectroscopy constitute suitable methods for drug quantification in SEDDS, which is promising for their use as process analytical technologies. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. High performance in silico virtual drug screening on many-core processors

    Science.gov (United States)

    Price, James; Sessions, Richard B; Ibarra, Amaurys A

    2015-01-01

    Drug screening is an important part of the drug development pipeline for the pharmaceutical industry. Traditional, lab-based methods are increasingly being augmented with computational methods, ranging from simple molecular similarity searches through more complex pharmacophore matching to more computationally intensive approaches, such as molecular docking. The latter simulates the binding of drug molecules to their targets, typically protein molecules. In this work, we describe BUDE, the Bristol University Docking Engine, which has been ported to the OpenCL industry standard parallel programming language in order to exploit the performance of modern many-core processors. Our highly optimized OpenCL implementation of BUDE sustains 1.43 TFLOP/s on a single Nvidia GTX 680 GPU, or 46% of peak performance. BUDE also exploits OpenCL to deliver effective performance portability across a broad spectrum of different computer architectures from different vendors, including GPUs from Nvidia and AMD, Intel’s Xeon Phi and multi-core CPUs with SIMD instruction sets. PMID:25972727

  9. Consumer's risk in the EMA and FDA regulatory approaches for bioequivalence in highly variable drugs.

    Science.gov (United States)

    Muñoz, Joel; Alcaide, Daniel; Ocaña, Jordi

    2016-05-30

    The 2010 US Food and Drug Administration and European Medicines Agency regulatory approaches to establish bioequivalence in highly variable drugs are both based on linearly scaling the bioequivalence limits, both take a 'scaled average bioequivalence' approach. The present paper corroborates previous work suggesting that none of them adequately controls type I error or consumer's risk, so they result in invalid test procedures in the neighbourhood of a within-subject coefficient of variation osf 30% for the reference (R) formulation. The problem is particularly serious in the US Food and Drug Administration regulation, but it is also appreciable in the European Medicines Agency one. For the partially replicated TRR/RTR/RRT and the replicated TRTR/RTRT crossover designs, we quantify these type I error problems by means of a simulation study, discuss their possible causes and propose straightforward improvements on both regulatory procedures that improve their type I error control while maintaining an adequate power. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  10. High performance in silico virtual drug screening on many-core processors.

    Science.gov (United States)

    McIntosh-Smith, Simon; Price, James; Sessions, Richard B; Ibarra, Amaurys A

    2015-05-01

    Drug screening is an important part of the drug development pipeline for the pharmaceutical industry. Traditional, lab-based methods are increasingly being augmented with computational methods, ranging from simple molecular similarity searches through more complex pharmacophore matching to more computationally intensive approaches, such as molecular docking. The latter simulates the binding of drug molecules to their targets, typically protein molecules. In this work, we describe BUDE, the Bristol University Docking Engine, which has been ported to the OpenCL industry standard parallel programming language in order to exploit the performance of modern many-core processors. Our highly optimized OpenCL implementation of BUDE sustains 1.43 TFLOP/s on a single Nvidia GTX 680 GPU, or 46% of peak performance. BUDE also exploits OpenCL to deliver effective performance portability across a broad spectrum of different computer architectures from different vendors, including GPUs from Nvidia and AMD, Intel's Xeon Phi and multi-core CPUs with SIMD instruction sets.

  11. High prevalence of drug-resistance mutations in Plasmodium falciparum and Plasmodium vivax in southern Ethiopia

    Directory of Open Access Journals (Sweden)

    Löscher Thomas

    2006-07-01

    Full Text Available Abstract Background In Ethiopia, malaria is caused by both Plasmodium falciparum and Plasmodium vivax. Drug resistance of P. falciparum to sulfadoxine-pyrimethamine (SP and chloroquine (CQ is frequent and intense in some areas. Methods In 100 patients with uncomplicated malaria from Dilla, southern Ethiopia, P. falciparum dhfr and dhps mutations as well as P. vivax dhfr polymorphisms associated with resistance to SP and P. falciparum pfcrt and pfmdr1 mutations conferring CQ resistance were assessed. Results P. falciparum and P. vivax were observed in 69% and 31% of the patients, respectively. Pfdhfr triple mutations and pfdhfr/pfdhps quintuple mutations occurred in 87% and 86% of P. falciparum isolates, respectively. Pfcrt T76 was seen in all and pfmdr1 Y86 in 81% of P. falciparum. The P. vivax dhfr core mutations N117 and R58 were present in 94% and 74%, respectively. Conclusion These data point to an extraordinarily high frequency of drug-resistance mutations in both P. falciparum and P. vivax in southern Ethiopia, and strongly support that both SP and CQ are inadequate drugs for this region.

  12. High intensity focused ultrasound technology, its scope and applications in therapy and drug delivery.

    Science.gov (United States)

    Phenix, Christopher Peter; Togtema, Melissa; Pichardo, Samuel; Zehbe, Ingeborg; Curiel, Laura

    2014-01-01

    Ultrasonography is a safe, inexpensive and wide-spread diagnostic tool capable of producing real-time non-invasive images without significant biological effects. However, the propagation of higher energy, intensity and frequency ultrasound waves through living tissues can induce thermal, mechanical and chemical effects useful for a variety of therapeutic applications. With the recent development of clinically approved High Intensity Focused Ultrasound (HIFU) systems, therapeutic ultrasound is now a medical reality. Indeed, HIFU has been used for the thermal ablation of pathological lesions; localized, minimally invasive ultrasound-mediated drug delivery through the transient formation of pores on cell membranes; the temporary disruption of skin and the blood brain barrier; the ultrasound induced break-down of blood clots; and the targeted release of drugs using ultrasound and temperature sensitive drug carriers. This review seeks to engage the pharmaceutical research community by providing an overview on the biological effects of ultrasound as well as highlighting important therapeutic applications, current deficiencies and future directions.

  13. Outcomes after chemotherapy with WHO category II regimen in a population with high prevalence of drug resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Francine Matthys

    Full Text Available Standard short course chemotherapy is recommended by the World Health Organization to control tuberculosis worldwide. However, in settings with high drug resistance, first line standard regimens are linked with high treatment failure. We evaluated treatment outcomes after standardized chemotherapy with the WHO recommended category II retreatment regimen in a prison with a high prevalence of drug resistant tuberculosis (TB. A cohort of 233 culture positive TB patients was followed through smear microscopy, culture, drug susceptibility testing and DNA fingerprinting at baseline, after 3 months and at the end of treatment. Overall 172 patients (74% became culture negative, while 43 (18% remained positive at the end of treatment. Among those 43 cases, 58% of failures were determined to be due to treatment with an inadequate drug regimen and 42% to either an initial mixed infection or re-infection while under treatment. Overall, drug resistance amplification during treatment occurred in 3.4% of the patient cohort. This study demonstrates that treatment failure is linked to initial drug resistance, that amplification of drug resistance occurs, and that mixed infection and re-infection during standard treatment contribute to treatment failure in confined settings with high prevalence of drug resistance.

  14. Supersaturation-nucleation behavior of poorly soluble drugs and its impact on the oral absorption of drugs in thermodynamically high-energy forms.

    Science.gov (United States)

    Ozaki, Shunsuke; Minamisono, Takuma; Yamashita, Taro; Kato, Takashi; Kushida, Ikuo

    2012-01-01

    In order to better understand the oral absorption behavior of poorly water-soluble drugs, their supersaturation-nucleation behavior was characterized in fasted state simulated intestinal fluid. The induction time (t(ind)) for nucleation was measured for four model drugs: itraconazole, erlotinib, troglitazone, and PLX4032. Supersaturated solutions were prepared by solvent shift method, and nucleation initiation was monitored by ultraviolet detection. The relationship between t(ind) and degree of supersaturation was analyzed in terms of classical nucleation theory. The defined supersaturation stability proved to be compound specific. Clinical data on oral absorption were investigated for drugs in thermodynamically high-energy forms such as amorphous forms and salts and was compared with in vitro supersaturation-nucleation characteristics. Solubility-limited maximum absorbable dose was proportionate to intestinal effective drug concentrations, which are related to supersaturation stability and thermodynamic solubility. Supersaturation stability was shown to be an important factor in determining the effect of high-energy forms. The characterization of supersaturation-nucleation behavior by the presented method is, therefore, valuable for assessing the potential absorbability of poorly water-soluble drugs. Copyright © 2011 Wiley-Liss, Inc.

  15. Self-double-emulsifying drug delivery system (SDEDDS): a new way for oral delivery of drugs with high solubility and low permeability.

    Science.gov (United States)

    Qi, Xiaole; Wang, Lishuang; Zhu, Jiabi; Hu, Zhenyi; Zhang, Jie

    2011-05-16

    Water-in-oil-in-water (w/o/w) double emulsions are potential for enhancing oral bioavailability of drugs with high solubility and low permeability, but their industrial application is limited due to the instability. Herein, we developed a novel formulation, self-double-emulsifying drug delivery systems (SDEDDS) by formulating mixtures of hydrophilic surfactants and water-in-oil (w/o) emulsions, which were easier to be stable through formulations optimization. SDEDDS can spontaneously emulsify to water-in-oil-in-water (w/o/w) double emulsions in the mixed aqueous gastrointestinal environment, with drugs encapsulated in the internal water phase of the double emulsions. We employed SDEDDS to improve the oral absorption of pidotimod, a peptide-like drug with high solubility and low permeability. The optimized pidotimod-SDEDDS were found to be stable up to 6 months under 25°C. Plasma concentration-time profiles from pharmacokinetic studies in rats dosed with SDEDDS showed 2.56-fold (p<0.05) increased absorption of pidotimod, compared to the pidotimod solution. Histopathologic studies confirmed that SDEDDS exerted absorption promoting effect without serious local damages. These studies demonstrate that SDEDDS may be a promising strategy for peroral delivery of peptide and peptidomimetic drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Addressing the challenge of high-priced prescription drugs in the era of precision medicine : a systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks.

    NARCIS (Netherlands)

    van der Gronde, T.; Uyl-de Groot, Carin A; Pieters, A.H.L.M.

    2017-01-01

    Context. Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. Method. A systematic review of Pubmed, the Financial Times,

  17. Addressing the challenge of high-priced prescription drugs in the era of precision medicine : A systematic review of drug life cycles, therapeutic drug markets and regulatory frameworks

    NARCIS (Netherlands)

    Gronde, T.V. (Toon van der); C.A. Uyl-de Groot (Carin); Pieters, T. (Toine)

    2017-01-01

    markdownabstractCONTEXT: Recent public outcry has highlighted the rising cost of prescription drugs worldwide, which in several disease areas outpaces other health care expenditures and results in a suboptimal global availability of essential medicines. METHOD: A systematic review of Pubmed, the

  18. Production and Investigation of Controlled Drug Release Properties of Tamoxifen Loaded Alginate-Gum Arabic Microbeads

    Directory of Open Access Journals (Sweden)

    Rukiye Yavaşer

    2016-08-01

    Full Text Available The entrapment of tamoxifen onto alginate-gum arabic beads and the production of controlled drug release was investigated in this study. The polymeric system that would provide the controlled release of tamoxifen was formed using alginate and gum arabic. In the first phase of the study, the optimization of the alginate-gum arabic beads production was conducted; then the study continued with drug entrapment experiments. Tamoxifen entrapment yield was found to be approximately 90% of initial tamoxifen concentration. In vitro drug release experiments were performed in simulated gastric juice and intestinal fluid where the tamoxifen release was 20% and 53% of the initial drug present, respectively. As a result of this study, it is expected that a valuable contribution to the field of controlled drug release system production is realized.

  19. Sustained ophthalmic delivery of highly soluble drug using pH-triggered inner layer-embedded contact lens.

    Science.gov (United States)

    Zhu, Qiang; Cheng, Hongbo; Huo, Yingnan; Mao, Shirui

    2018-06-10

    In the present work the feasibility of using inner layer-embedded contact lenses (CLs) to achieve sustained release of highly water soluble drug, betaxolol hydrochloride (BH) on the ocular surface was investigated. Blend film of cellulose acetate and Eudragit S100 was selected as the inner layer, while silicone hydrogel was used as outer layer to construct inner layer-embedded contact lenses. Influence of polymer ratio in the blend film on in vitro drug release behavior in phosphate buffered solution or simulated tear fluid was studied and drug-polymer interaction, erosion and swelling of the blend film were characterized to better understand drug-release mechanism. Storage stability of the inner layer-embedded contact lenses in phosphate buffer solution was also conducted, with ignorable drug loss and negligible change in drug release pattern within 30 days. In vivo pharmacokinetic study in rabbits showed sustained drug release for over 240 h in tear fluid, indicating prolonged drug precorneal residence time. In conclusion, cellulose acetate/Eudragit S100 inner layer-embedded contact lenses are quite promising as controlled-release carrier of highly water soluble drug for ophthalmic delivery. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Role of magnetic resonance imaging in entrapment and compressive neuropathy - what, where, and how to see the peripheral nerves on the musculoskeletal magnetic resonance image: part 1. Overview and lower extremity

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sungjun [Yonsei University, Department of Diagnostic Radiology, College of Medicine, Seoul (Korea); Hanyang University, Kuri Hospital, Department of Diagnostic Radiology, College of Medicine, Kuri City, Kyunggi-do (Korea); Choi, Jin-Young; Huh, Yong-Min; Song, Ho-Taek; Lee, Sung-Ah [Yonsei University, Department of Diagnostic Radiology, College of Medicine, Seoul (Korea); Kim, Seung Min [Yonsei University, Department of Neurology, College of Medicine, Seoul (Korea); Suh, Jin-Suck [Yonsei University, Department of Diagnostic Radiology, College of Medicine, Seoul (Korea); Yonsei University, Research Institute of Radiological Science, College of Medicine, Seoul (Korea)

    2007-01-15

    The diagnosis of nerve entrapment and compressive neuropathy has been traditionally based on the clinical and electrodiagnostic examinations. As a result of improvements in the magnetic resonance (MR) imaging modality, it plays not only a fundamental role in the detection of space-occupying lesions but also a compensatory role in clinically and electrodiagnostically inconclusive cases. Although ultrasound has undergone further development in the past decades and shows high resolution capabilities, it has inherent limitations due to its operator dependency. We review the general concepts that should be known to evaluate the entrapment and compressive neuropathy in MR imaging. We also review the course of normal peripheral nerves, as well as various clinical demonstrations and pathological features of compressed and entrapped nerves in the lower extremities on MR imaging, according to the nerves involved. The common sites of nerve entrapment of the lower extremity are as follows: sciatic nerve around the piriformis muscle; tibial nerve at the popliteal fossa and tarsal tunnel, common peroneal nerve around the fibular neck, and digital nerve near the metatarsal head. Although MR imaging can depict the peripheral nerves in the extremities effectively, radiologists should be familiar with nerve pathways, common sites of nerve compression, and common space-occupying lesions resulting in nerve compression in MR imaging. (orig.)

  1. Role of magnetic resonance imaging in entrapment and compressive neuropathy - what, where, and how to see the peripheral nerves on the musculoskeletal magnetic resonance image: part 1. Overview and lower extremity

    International Nuclear Information System (INIS)

    Kim, Sungjun; Choi, Jin-Young; Huh, Yong-Min; Song, Ho-Taek; Lee, Sung-Ah; Kim, Seung Min; Suh, Jin-Suck

    2007-01-01

    The diagnosis of nerve entrapment and compressive neuropathy has been traditionally based on the clinical and electrodiagnostic examinations. As a result of improvements in the magnetic resonance (MR) imaging modality, it plays not only a fundamental role in the detection of space-occupying lesions but also a compensatory role in clinically and electrodiagnostically inconclusive cases. Although ultrasound has undergone further development in the past decades and shows high resolution capabilities, it has inherent limitations due to its operator dependency. We review the general concepts that should be known to evaluate the entrapment and compressive neuropathy in MR imaging. We also review the course of normal peripheral nerves, as well as various clinical demonstrations and pathological features of compressed and entrapped nerves in the lower extremities on MR imaging, according to the nerves involved. The common sites of nerve entrapment of the lower extremity are as follows: sciatic nerve around the piriformis muscle; tibial nerve at the popliteal fossa and tarsal tunnel, common peroneal nerve around the fibular neck, and digital nerve near the metatarsal head. Although MR imaging can depict the peripheral nerves in the extremities effectively, radiologists should be familiar with nerve pathways, common sites of nerve compression, and common space-occupying lesions resulting in nerve compression in MR imaging. (orig.)

  2. Pharmacodynamics of diclofenac from novel Eudragit entrapped microspheres.

    Science.gov (United States)

    Momoh, M A; Kenechukwu, F C; Adedokun, M O; Odo, C E; Attama, A A

    2014-05-01

    Effective clinical utilization of non-steroidal anti-inflammatory drugs such as diclofenac sodium (DS) is significantly limited by their ulcerogenic potential and poor bioavailability after oral administration, thus necessitating the need for a better carrier to minimize these obvious limitations. The objective of this study was to evaluate Eudragit® RS100/RL100 microspheres formulated by the solvent-evaporation technique for improved delivery of diclofenac. Three batches of (DF1, DF2 and DF3) microspheres were prepared using different ratios of Eudragit RS-100 and RL-100 polymers based on the solvent-evaporation method. The microspheres were characterized based on morphological properties, particle size analysis and encapsulation efficiency (EE%). In vitro release of DS was investigated in both 0.1 N HCl (pH 1.2) and phosphate-buffered saline (pH 7.4), while anti-inflammatory studies were evaluated in the rat model. Maximum EE% of 86.61 ± 0.11, 88.14 ± 0.16 and 85.50 ± 0.21 was obtained for DF1, DF2 and DF3, respectively. Discrete, smooth and brownish microspheres of size range 437 ± 0.01-479 ± 0.21 µm were obtained. Release of DS from the formulation depends on the polymer ratio. All the batches exhibited good anti-inflammatory activities. Microsphere formulations based on Eudragit® polymers would likely offer a reliable and alternative means of delivering DS orally.

  3. Evaluation of chitosan–anionic polymers based tablets for extended-release of highly water-soluble drugs

    Directory of Open Access Journals (Sweden)

    Yang Shao

    2015-02-01

    Full Text Available The objective of this study is to develop chitosan–anionic polymers based extended-release tablets and test the feasibility of using this system for the sustained release of highly water-soluble drugs with high drug loading. Here, the combination of sodium valproate (VPS and valproic acid (VPA were chosen as the model drugs. Anionic polymers studied include xanthan gum (XG, carrageenan (CG, sodium carboxymethyl cellulose (CMC-Na and sodium alginate (SA. The tablets were prepared by wet granulation method. In vitro drug release was carried out under simulated gastrointestinal condition. Drug release mechanism was studied. Compared with single polymers, chitosan–anionic polymers based system caused a further slowdown of drug release rate. Among them, CS–xanthan gum matrix system exhibited the best extended-release behavior and could extend drug release for up to 24 h. Differential scanning calorimetry (DSC and Fourier transform infrared spectroscopy (FTIR studies demonstrated that polyelectrolyte complexes (PECs were formed on the tablet surface, which played an important role on retarding erosion and swelling of the matrix in the later stage. In conclusion, this study demonstrated that it is possible to develop highly water-soluble drugs loaded extended-release tablets using chitosan–anionic polymers based system.

  4. The Prevalence of Tobacco, Hubble-Bubble, Alcoholic Drinks, Drugs, and Stimulants among High-School Students

    Directory of Open Access Journals (Sweden)

    Roghayeh Alaee

    2011-08-01

    Full Text Available Introduction: The purpose of the present study was to investigate the prevalence of tobacco, hubble-bubble, alcoholic drinks, and other drugs among Karaj high-school students in 2011. Methods: The research method was a descriptive-sectional study. Participants of this study were 447 girl and boy high-school students of Karaj that were selected by clustering random sampling. For data gathering, drug abuse questionnaire, and risk and protective factors inventory were administered among selected sample. Results: According to the results, 57% of students in this study said that they have had experiences with a kind of drug including tobacco, hubble-bubble, alcoholic drinks, and other drugs at least once in their lives. The study showed the prevalence for soft drugs: hubble-bubble, tobacco, and alcoholic drinks, and for hard drugs ecstasy, opium, hashish, meth, crack, and heroin respectively. Conclusion: Soft drugs including hubble-bubble, tobacco, and alcoholic drinks, are the most common among Karaj high-school students. The prevalence of hard drugs among them is rather low.

  5. Label-free detection of cellular drug responses by high-throughput bright-field imaging and machine learning.

    Science.gov (United States)

    Kobayashi, Hirofumi; Lei, Cheng; Wu, Yi; Mao, Ailin; Jiang, Yiyue; Guo, Baoshan; Ozeki, Yasuyuki; Goda, Keisuke

    2017-09-29

    In the last decade, high-content screening based on multivariate single-cell imaging has been proven effective in drug discovery to evaluate drug-induced phenotypic variations. Unfortunately, this method inherently requires fluorescent labeling which has several drawbacks. Here we present a label-free method for evaluating cellular drug responses only by high-throughput bright-field imaging with the aid of machine learning algorithms. Specifically, we performed high-throughput bright-field imaging of numerous drug-treated and -untreated cells (N = ~240,000) by optofluidic time-stretch microscopy with high throughput up to 10,000 cells/s and applied machine learning to the cell images to identify their morphological variations which are too subtle for human eyes to detect. Consequently, we achieved a high accuracy of 92% in distinguishing drug-treated and -untreated cells without the need for labeling. Furthermore, we also demonstrated that dose-dependent, drug-induced morphological change from different experiments can be inferred from the classification accuracy of a single classification model. Our work lays the groundwork for label-free drug screening in pharmaceutical science and industry.

  6. Anatomical etiology of “pseudo-sciatica” from superior cluneal nerve entrapment: a laboratory investigation

    Directory of Open Access Journals (Sweden)

    Konno T

    2017-11-01

    Full Text Available Tomoyuki Konno,1 Yoichi Aota,2 Hiroshi Kuniya,1 Tomoyuki Saito,1 Ning Qu,3 Shogo Hayashi,3 Shinichi Kawata,3 Masahiro Itoh3 1Department of Orthopaedic Surgery, Yokohama City University Graduate School of Medicine, 2Department of Spine & Spinal Cord Surgery, Yokohama Brain and Spine Center, Yokohama, 3Department of Anatomy, Tokyo Medical University, Tokyo, Japan Objective: The superior cluneal nerve (SCN may become entrapped where it pierces the thoracolumbar fascia over the iliac crest; this can cause low back pain (LBP and referred pain radiating into the posterior thigh, calf, and occasionally the foot, producing the condition known as “pseudo-sciatica.” Because the SCN was thought to be a cutaneous branch of the lumbar dorsal rami, originating from the dorsal roots of L1–L3, previous anatomical studies failed to explain why SCN causes “pseudo-sciatica”. The purpose of the present anatomical study was to better elucidate the anatomy and improve the understanding of “pseudo-sciatica” from SCN entrapment. Materials and methods: SCN branches were dissected from their origin to termination in subcutaneous tissue in 16 cadavers (5 male and 11 female with a mean death age of 88 years (range 81–101 years. Special attention was paid to identify SCNs from their emergence from nerve roots and passage through the fascial attachment to the iliac crest. Results: Eighty-one SCN branches were identified originating from T12 to L5 nerve roots with 13 branches passing through the osteofibrous tunnel. These 13 branches originated from L3 (two sides, L4 (six sides, and L5 (five sides. Ten of the 13 branches showed macroscopic entrapment in the tunnel. Conclusion: The majority of SCNs at risk of nerve entrapment originated from the lower lumbar nerve. These anatomical results may explain why patients with SCN entrapment often evince leg pain or tingling that mimics sciatica. Keywords: superior cluneal nerve, entrapment neuropathy, dorsal rami

  7. Development of novel, 384-well high-throughput assay panels for human drug transporters: drug interaction and safety assessment in support of discovery research.

    Science.gov (United States)

    Tang, Huaping; Shen, Ding Ren; Han, Yong-Hae; Kong, Yan; Balimane, Praveen; Marino, Anthony; Gao, Mian; Wu, Sophie; Xie, Dianlin; Soars, Matthew G; O'Connell, Jonathan C; Rodrigues, A David; Zhang, Litao; Cvijic, Mary Ellen

    2013-10-01

    Transporter proteins are known to play a critical role in affecting the overall absorption, distribution, metabolism, and excretion characteristics of drug candidates. In addition to efflux transporters (P-gp, BCRP, MRP2, etc.) that limit absorption, there has been a renewed interest in influx transporters at the renal (OATs, OCTs) and hepatic (OATPs, BSEP, NTCP, etc.) organ level that can cause significant clinical drug-drug interactions (DDIs). Several of these transporters are also critical for hepatobiliary disposition of bilirubin and bile acid/salts, and their inhibition is directly implicated in hepatic toxicities. Regulatory agencies took action to address transporter-mediated DDI with the goal of ensuring drug safety in the clinic and on the market. To meet regulatory requirements, advanced bioassay technology and automation solutions were implemented for high-throughput transporter screening to provide structure-activity relationship within lead optimization. To enhance capacity, several functional assay formats were miniaturized to 384-well throughput including novel fluorescence-based uptake and efflux inhibition assays using high-content image analysis as well as cell-based radioactive uptake and vesicle-based efflux inhibition assays. This high-throughput capability enabled a paradigm shift from studying transporter-related issues in the development space to identifying and dialing out these concerns early on in discovery for enhanced mechanism-based efficacy while circumventing DDIs and transporter toxicities.

  8. Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process.

    Science.gov (United States)

    Pandey, Preetanshu; Levins, Christopher; Pafiakis, Steve; Zacour, Brian; Bindra, Dilbir S; Trinh, Jade; Buckley, David; Gour, Shruti; Sharif, Shasad; Stamato, Howard

    2018-07-01

    The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2 (4-1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p = .0009), inlet T (p = .0062), atomization air pressure (p = .0134) and the interaction effect between inlet T*spray rate (p = .0241). The compactibility of the final blend was affected significantly by disintegrant amount (p disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.

  9. IMPACT OF HEALTH TECHNOLOGY ASSESSMENT IN LITIGATION CONCERNING ACCESS TO HIGH-COST DRUGS.

    Science.gov (United States)

    Aleman, Alicia; Perez Galan, Ana

    2017-01-01

    The impact of health technology assessment (HTA) in the judicialization of the right of health has not been deeply studied in Latin American countries. The purpose of this study is to review the process of judicialization of the access to high cost drugs in Uruguay and assess the impact HTAs have had on this process. The methodology used for this study included a comprehensive literature search in electronic databases, local journals, internal documents developed in the Ministry of Health, as well as conducting interviews with key informants. Judicialization of the access of high cost drugs has been increasing since 2010. The strategy of the Ministry of Health of Uruguay to decrease this problem included the organization of roundtables with judges and other stakeholders on the basis of HTA, the training of defense lawyers in the use and interpretation of HTA, and the participation of a professional who develops HTA in the preparation of the defense arguments. A year after the implementation of this strategy, 25 percent of writs of protection were won by the Ministry of Health. Even though the strategy implemented was effective in reducing the loss of litigations, it was not effective in reducing the growing number of writs of protection. It is essential to address this problem in a broad debate and to promote understanding between the parties.

  10. Repurposing High-Throughput Image Assays Enables Biological Activity Prediction for Drug Discovery.

    Science.gov (United States)

    Simm, Jaak; Klambauer, Günter; Arany, Adam; Steijaert, Marvin; Wegner, Jörg Kurt; Gustin, Emmanuel; Chupakhin, Vladimir; Chong, Yolanda T; Vialard, Jorge; Buijnsters, Peter; Velter, Ingrid; Vapirev, Alexander; Singh, Shantanu; Carpenter, Anne E; Wuyts, Roel; Hochreiter, Sepp; Moreau, Yves; Ceulemans, Hugo

    2018-05-17

    In both academia and the pharmaceutical industry, large-scale assays for drug discovery are expensive and often impractical, particularly for the increasingly important physiologically relevant model systems that require primary cells, organoids, whole organisms, or expensive or rare reagents. We hypothesized that data from a single high-throughput imaging assay can be repurposed to predict the biological activity of compounds in other assays, even those targeting alternate pathways or biological processes. Indeed, quantitative information extracted from a three-channel microscopy-based screen for glucocorticoid receptor translocation was able to predict assay-specific biological activity in two ongoing drug discovery projects. In these projects, repurposing increased hit rates by 50- to 250-fold over that of the initial project assays while increasing the chemical structure diversity of the hits. Our results suggest that data from high-content screens are a rich source of information that can be used to predict and replace customized biological assays. Copyright © 2018 Elsevier Ltd. All rights reserved.

  11. Reducing risk for illicit drug use and prescription drug misuse: High school gay-straight alliances and lesbian, gay, bisexual, and transgender youth.

    Science.gov (United States)

    Heck, Nicholas C; Livingston, Nicholas A; Flentje, Annesa; Oost, Kathryn; Stewart, Brandon T; Cochran, Bryan N

    2014-04-01

    Previous research suggests that lesbian, gay, bisexual, and transgender (LGBT) youth are at elevated risk for using illicit drugs and misusing prescription drugs relative to heterosexual youth. Previous research also indicates that LGBT youth who attend high schools with a gay-straight alliance (GSA) report having fewer alcohol problems and lower levels of cigarette smoking. The present study investigates whether the absence of a GSA is associated with risk for illicit drug use and prescription drug misuse in a sample of 475 LGBT high school students (M age=16.79) who completed an online survey. After controlling for demographic variables and risk factors associated with illicit drug use, the results of 12 logistic regression analyses revealed that LGBT youth attending a high school without a GSA evidenced increased risk for using cocaine (adjusted odds ratio [adjOR]=3.11; 95% confidence interval [95% CI]=1.23-7.86), hallucinogens (adjOR=2.59; 95% CI=1.18-5.70), and marijuana (adjOR=2.22; 95% CI=1.37-3.59) relative to peers attending a high school with a GSA. Youth without a GSA also evidenced increased risk for the misuse of ADHD medication (adjOR=2.00; 95% CI=1.02-3.92) and prescription pain medication (adjOR=2.00; 95% CI=1.10-3.65). These findings extend the research base related to GSAs and further demonstrate the importance of providing LGBT youth with opportunities for socialization and support within the school setting. Important limitations of the present study are reviewed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. High-throughput untargeted screening of veterinary drug residues and metabolites in tilapia using high resolution orbitrap mass spectrometry.

    Science.gov (United States)

    Jia, Wei; Chu, Xiaogang; Chang, James; Wang, Perry G; Chen, Ying; Zhang, Feng

    2017-03-08

    An analytical method was developed and validated for simultaneous analysis of one hundred and thirty-seven veterinary drug residues and metabolites from sixteen different classes in tilapia utilizing an improved fully non-targeted way of data acquisition with fragmentation. The automated on-line extraction procedure was achieved in a simple disposable pipet extraction. Ultrahigh-performance liquid chromatography and electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC Q-Orbitrap) was used for the separation and detection of all the analytes. The methodology was validated by taking into consideration the guidelines specified in European SANCO/12571/2013 Guideline 2013 and Commission Decision 2002/657/EC. The extraction recoveries ranged from 81% to 111%. The limits of decision ranged from 0.01 to 2.73 μg kg -1 and the detection capabilities ranged from 0.01 to 4.73 μg kg -1 . The one hundred and thirty-seven compounds behave dynamic 0.1-500 μg kg -1 , with correlation coefficient >0.99. The fully non-targeted data acquisition way improves both sensitivity and selectivity for the fragments, which is beneficial for screening performance and identification capability. This validated method has been successfully applied on screening of veterinary drug residues and metabolites in muscle of tilapia, an important and intensively produced fish in aquaculture. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Ultra-high-performance liquid chromatography-Time-of-flight high resolution mass spectrometry to quantify acidic drugs in wastewater.

    Science.gov (United States)

    Becerra-Herrera, Mercedes; Honda, Luis; Richter, Pablo

    2015-12-04

    A novel analytical approach involving an improved rotating-disk sorptive extraction (RDSE) procedure and ultra-high-performance liquid chromatography (UHPLC) coupled to an ultraspray electrospray ionization source (UESI) and time-of-flight mass spectrometry (TOF/MS), in trap mode, was developed to identify and quantify four non-steroidal anti-inflammatory drugs (NSAIDs) (naproxen, ibuprofen, ketoprofen and diclofenac) and two anti-cholesterol drugs (ACDs) (clofibric acid and gemfibrozil) that are widely used and typically found in water samples. The method reduced the amount of both sample and reagents used and also the time required for the whole analysis, resulting in a reliable and green analytical strategy. The analytical eco-scale was calculated, showing that this methodology is an excellent green analysis, increasing its ecological worth. The detection limits (LOD) and precision (%RSD) were lower than 90ng/L and 10%, respectively. Matrix effects and recoveries were studied using samples from the influent of a wastewater treatment plant (WWTP). All the compounds exhibited suppression of their signals due to matrix effects, and the recoveries were approximately 100%. The applicability and reliability of this methodology were confirmed through the analysis of influent and effluent samples from a WWTP in Santiago, Chile, obtaining concentrations ranging from 1.1 to 20.5μg/L and from 0.5 to 8.6μg/L, respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Dual functions of polyvinyl alcohol (PVA): fabricating particles and electrospinning nanofibers applied in controlled drug release

    Science.gov (United States)

    Qin, Xiao-Hong; Wu, De-Qun; Chu, Chih-Chang

    2013-01-01

    The fabrication of submicron size microsphere from 8-Phe-4 poly(ester amide) (PEA) using polyvinyl alcohol (PVA) as the emulsion was reported. The biodegradable microspheres were prepared by an oil-in-water emulsion/solvent evaporation technique, and PVA was used as the emulsion. Furthermore, the emulsion PVA was electrospun into nanofibrous mats, and 8-Phe-4 PEA microspheres were entrapped in the resultant mats. The dual functions of PVA to fabricate ideal nanofibrous mats which can entrap microspheres in them and to obtain 8-Phe-4 microspheres as emulsion in their potential application were demonstrated. The anti-cancer drug doxorubicin (DOX) was encapsulated in the 8-Phe-4 amino acid-based PEA microspheres and the entrapment efficiency is almost 100 %. At the same time, the DOX can be controlled released in PBS solution and in α-chymotrypsin solution. The cytotoxicity of PVA, PVA mats-entrapped 8-Phe-4 microspheres and PVA mats-entrapped DOX-loaded 8-Phe-4 microspheres, was investigated. Hela cells were used to test the cytotoxicity of the DOX that released from the PVA mats-entrapped DOX-loaded 8-Phe-4 microspheres for 2 days, and the cell viability is below 30 % when the 8-Phe-4 microspheres concentration is 1 mg/mL. It demonstrated that the PVA mats-entrapped DOX-loaded 8-Phe-4 microspheres have a potential biomedical application.

  15. Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.

    Science.gov (United States)

    Kralberg, B E; Tolagen, K

    1976-05-31

    The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin

  16. Continued high prevalence of HIV, HBV and HCV among injecting and noninjecting drug users in Italy

    Directory of Open Access Journals (Sweden)

    Laura Camoni

    2010-03-01

    Full Text Available We estimated the prevalence of HIV, HBV and HCV infections among injecting and non-injecting drug users treated within public drug-treatment centres in Italy to determine the correlates of infection. In the sample of 1330 drug users, the prevalence of HIV was 14.4% among drug injectors and 1.6% among non-injectors; the prevalence of HBV was 70.4% among injecting drug users and 22.8% among non-injectors and of HCV was 83.2% among injecting drug users and 22.0% among non-injectors. Old age, unemployment, and intravenous drug use were significantly correlated with each of the infections, as well as a longer history of injecting drug use. The results indicate that these infections continue to circulate among drug users, highlighting the need for monitoring of this group in Italy.

  17. High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations

    Science.gov (United States)

    Mott, Bryan T.; Eastman, Richard T.; Guha, Rajarshi; Sherlach, Katy S.; Siriwardana, Amila; Shinn, Paul; McKnight, Crystal; Michael, Sam; Lacerda-Queiroz, Norinne; Patel, Paresma R.; Khine, Pwint; Sun, Hongmao; Kasbekar, Monica; Aghdam, Nima; Fontaine, Shaun D.; Liu, Dongbo; Mierzwa, Tim; Mathews-Griner, Lesley A.; Ferrer, Marc; Renslo, Adam R.; Inglese, James; Yuan, Jing; Roepe, Paul D.; Su, Xin-zhuan; Thomas, Craig J.

    2015-01-01

    Drug resistance in Plasmodium parasites is a constant threat. Novel therapeutics, especially new drug combinations, must be identified at a faster rate. In response to the urgent need for new antimalarial drug combinations we screened a large collection of approved and investigational drugs, tested 13,910 drug pairs, and identified many promising antimalarial drug combinations. The activity of known antimalarial drug regimens was confirmed and a myriad of new classes of positively interacting drug pairings were discovered. Network and clustering analyses reinforced established mechanistic relationships for known drug combinations and identified several novel mechanistic hypotheses. From eleven screens comprising >4,600 combinations per parasite strain (including duplicates) we further investigated interactions between approved antimalarials, calcium homeostasis modulators, and inhibitors of phosphatidylinositide 3-kinases (PI3K) and the mammalian target of rapamycin (mTOR). These studies highlight important targets and pathways and provide promising leads for clinically actionable antimalarial therapy. PMID:26403635

  18. RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance

    Directory of Open Access Journals (Sweden)

    Richard J. Bingham

    2017-11-01

    Full Text Available The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design.

  19. RNA Virus Evolution via a Quasispecies-Based Model Reveals a Drug Target with a High Barrier to Resistance.

    Science.gov (United States)

    Bingham, Richard J; Dykeman, Eric C; Twarock, Reidun

    2017-11-17

    The rapid occurrence of therapy-resistant mutant strains provides a challenge for anti-viral therapy. An ideal drug target would be a highly conserved molecular feature in the viral life cycle, such as the packaging signals in the genomes of RNA viruses that encode an instruction manual for their efficient assembly. The ubiquity of this assembly code in RNA viruses, including major human pathogens, suggests that it confers selective advantages. However, their impact on viral evolution cannot be assessed in current models of viral infection that lack molecular details of virus assembly. We introduce here a quasispecies-based model of a viral infection that incorporates structural and mechanistic knowledge of packaging signal function in assembly to construct a phenotype-fitness map, capturing the impact of this RNA code on assembly yield and efficiency. Details of viral replication and assembly inside an infected host cell are coupled with a population model of a viral infection, allowing the occurrence of therapy resistance to be assessed in response to drugs inhibiting packaging signal recognition. Stochastic simulations of viral quasispecies evolution in chronic HCV infection under drug action and/or immune clearance reveal that drugs targeting all RNA signals in the assembly code collectively have a high barrier to drug resistance, even though each packaging signal in isolation has a lower barrier than conventional drugs. This suggests that drugs targeting the RNA signals in the assembly code could be promising routes for exploitation in anti-viral drug design.

  20. An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a Poorly Soluble Drug with a Low Melting Surfactant.

    Science.gov (United States)

    Tatavarti, Aditya; Kesisoglou, Filippos

    2015-11-01

    Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface active agent, known to enhance the bioavailability of lipophilic compounds via wettability, solubility, and in some cases permeability enhancement. MK-0536 is an anti-retroviral drug with poor wettability and solubility and a high dose. Based on pharmacokinetic studies in dogs and humans, use of vitamin E TPGS in oral solid formulations of MK-0536 provides desired PK characteristics. The use of vitamin E TPGS, however, in solid dosage forms is limited because of the processing challenges resulting from its waxy nature and low melting temperature (∼37°C). The current study, for the first time, demonstrates the use of an alternative low pressure extrusion and spheronization approach to enable high loadings of the poorly soluble, poorly compactable drug and relatively high levels of vitamin E TPGS. This approach not only aided in mitigating processing challenges arising from most high energy process steps such as milling, compression, and coating, but also enabled a higher drug load formulation that provided superior bioperformance relative to a conventional high shear wet granulated formulation. An encapsulated dosage form consisting of pellets prepared by extrusion spheronization with 75% (w/w) MK-0536 and 10% (w/w) vitamin E TPGS was developed. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  1. A trap for the unwary: jury decision making in cases involving the entrapment defense.

    Science.gov (United States)

    Peters, Christopher S; Lampinen, James Michael; Malesky, L Alvin

    2013-02-01

    This article examines the opinions of jury-eligible participants regarding entrapment-related issues in online sex offender sting operations. Participants provided lower guilt ratings when the undercover officer initiated the online sexual solicitation than when the defendant initiated the online sexual solicitation. This effect was mediated by the causal attributions (situational vs. dispositional) made by mock jurors for the defendant's actions. The results also suggested that the entrapment defense was less successful for participants with a crime control orientation than for participants with a due process orientation. Based on the results, it is implied that law enforcement should exercise caution when performing these types of sting operations. Furthermore, defense and prosecuting attorneys should take into account the originators of the sexual solicitation when deciding whether to plea bargain or take a case to trial.

  2. Entrapment of peptidoglycans and adamantyltripeptides into liposomes: an HPLC assay for determination of encapsulation efficiency.

    Science.gov (United States)

    Frkanec, Ruza; Travas, Dijana; Krstanović, Marina; Spoljar, Beata Halassy; Ljevaković, Durdica; Vranesić, Branka; Frkanec, Leo; Tomasić, Jelka

    2003-11-01

    The encapsulation of different immunomodulating peptides, the peptidoglycan monomer, its semisynthetic derivatives (Adamant-1-yl)-acetyl-peptidoglycan monomer and Boc-Tyr-peptidoglycan monomer, respectively, and of two diastereoisomers of adamantyltripeptides into the large negatively charged multilamellar liposomes was investigated. The reproducible quantitative method using HPLC was established for the determination of the entrapped compounds. It was shown that the tested compounds could be efficiently incorporated into liposomes using either the film or modified film method. The results confirmed that the peptidoglycans with lipophilic substituents and particularly the adamantyltripeptides were incorporated into liposomes with higher efficiency than the peptidoglycan monomer using either of the described methods. Liposome preparations were stable at 4 degrees C up to seven days as shown by minimal leaking of the entrapped material.

  3. A simple approach to the prediction of waterhammer transients in a pipe line with entrapped air

    International Nuclear Information System (INIS)

    Epstein, Michael

    2008-01-01

    The pressure histories within entrapped air bubbles in a pipe line during a waterhammer transient are treated theoretically. A convenient integral method is introduced, which takes full account of air/water interface movement and liquid compressibility. The significance of the method is that it provides a simple equation set for approximating, with good accuracy and with a small degree of conservatism, the solution to a problem that otherwise involves coupled partial differential equations on time dependent domains with non-linear boundary conditions. The accuracy of the method is defined by its comparison with available numerical-solution-predictions and measurements of the pressure within an entrapped-air-bubble at a dead end in a pipe. The method is shown to be a computationally simple and efficient way of assessing the impact of liquid compressibility on pressure rise when multiple water columns and air pockets are present in a pipe line

  4. Inhibitory effect of liposome-entrapped lemongrass oil on the growth of Listeria monocytogenes in cheese.

    Science.gov (United States)

    Cui, H Y; Wu, J; Lin, L

    2016-08-01

    Listeria monocytogenes infection in dairy products is of mounting public concern. To inhibit bacterial growth, we engineered stimuli-responsive liposomes containing lemongrass oil for this study. The controlled release of liposome-entrapped lemongrass oil is triggered by listerolysin O, secreted by L. monocytogenes. We investigated the antibiotic activities of lemongrass oil liposomes against L. monocytogenes in cheese. We also assessed their possible effects on the quality of the cheese. Liposomes containing lemongrass oil (5.0mg/mL) presented the optimal polydispersity index (0.246), zeta-potential (-58.9mV) and entrapment efficiency (25.7%). The liposomes displayed satisfactory antibiotic activity against L. monocytogenes in cheese over the storage period at 4°C. We observed no effects on the physical and sensory properties of the cheese after the liposome treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  5. United States v. Levin: entrapment by estoppel doctrine applied in Medicare reimbursement context.

    Science.gov (United States)

    Shaw, P W; Griffith, R A

    1993-01-01

    The decision in Levin reaffirms that health care providers should be entitled to rely in good faith on official interpretations and representations by authorized government officials as to the propriety of their conduct under the Medicare program. Although the doctrine of entrapment by estoppel was developed as a due process defense to a criminal prosecution, the fundamental notions of fairness underlying the doctrine should be applicable as well as in a civil action. Thus, the defense of entrapment by estoppel should be available, for example, in the context of civil health care reimbursement recoupment audits, where a provider has acted in reliance on the interpretation of a statute or regulation by the appropriate administrative agency charged with its enforcement.

  6. Ultrasound-Stimulated Drug Delivery Using Therapeutic Reconstituted High-Density Lipoprotein Nanoparticles.

    Science.gov (United States)

    Xiong, Fangyuan; Nirupama, Sabnis; Sirsi, Shashank R; Lacko, Andras; Hoyt, Kenneth

    2017-01-01

    The abnormal tumor vasculature and the resulting abnormal microenvironment are major barriers to optimal chemotherapeutic drug delivery. It is well known that ultrasound (US) can increase the permeability of the tumor vessel walls and enhance the accumulation of anticancer agents. Reconstituted high-density lipoproteins (rHDL) nanoparticles (NPs) allow selective delivery of anticancer agents to tumor cells via their overexpressed scavenger receptor type B1 (SR-B1) receptor. The goal of this study is to investigate the potential of noninvasive US therapy to further improve delivery and tumor uptake of the payload from rHDL NPs, preloaded with an infrared dye (IR-780), aimed to establish a surrogate chemotherapeutic model with optical localization. Athymic nude mice were implanted orthotopically with one million breast cancer cells (MDA-MB-231/Luc). Three weeks later, animals were divided into seven groups with comparable mean tumor size: control, low, moderate, and high concentration of rHDL NPs alone groups, as well as these three levels of rHDL NPs plus US therapy groups ( N = 7 to 12 animals per group), where low, moderate and high denote 5, 10, and 50 µg of the IR-780 dye payload per rHDL NP injection, respectively. The US therapy system included a single element focused transducer connected in series with a function generator and power amplifier. A custom 3D printed cone with an acoustically transparent aperture and filled with degassed water allowed delivery of focused US energy to the tumor tissue. US exposure involved a pulsed sequence applied for a duration of 5 min. Each animal in the US therapy groups received a slow bolus co-injection of MB contrast agent and rHDL NPs. Animals were imaged using a whole-body optical system to quantify intratumoral rHDL NP accumulation at baseline and again at 1 min, 30 min, 24 h, and 48 h. At 48 h, all animals were euthanized and tumors were excised for ex vivo analysis. We investigated a noninvasive optical imaging

  7. Dilute-and-shoot coupled to nanoflow liquid chromatography high resolution mass spectrometry for the determination of drugs of abuse and sport drugs in human urine.

    Science.gov (United States)

    Alcántara-Durán, Jaime; Moreno-González, David; Beneito-Cambra, Miriam; García-Reyes, Juan F

    2018-05-15

    In this work, a sensitive nanoflow liquid chromatography high-resolution mass spectrometry screening method has been developed for the determination of multiclass drugs of abuse and sport drugs in human urine. 81 drugs belonging to different multiclass pharmaceuticals were targeted. The method is based on the use of a nanoLC column (75 µm × 150 mm, 3 µm particle size and 100 Å pore) with the nanospray emitter tip integrated so that dead volumes are significantly minimized. Data acquisition method included both full-scan and all ion fragmentation experiments using an Orbitrap analyser (Q-Exactive) operated in the positive ionization mode. To increase laboratory throughput, a dilute-and-shoot methodology has been tested and proposed, based solely on direct urine dilution without further sample workup. Matrix effects were evaluated, showing a negligible effect for all studied compounds when a dilution 1:50 was implemented. Despite this high-dilution factor, limits of quantification were still satisfactory, with values below 5 µg L -1 in most cases, being lower than their minimum required performance limits correspond established by the World Anti-Doping Agency. Therefore, the use of the dilute-and-shoot method with the enhanced sensitivity provided by nanoflow LC setup could be useful tool for the determination of studied compounds in drug testing, thus increasing laboratory performance, because a minimum sample treatment steps are required. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. High notes: the role of drugs in the making of Jazz.

    Science.gov (United States)

    Singer, Merrill; Mirhej, Greg

    2006-01-01

    This paper examines the role played by illicit drugs, especially marijuana and heroin, in the historic development and evolution of Jazz in the United States during the twentieth century. In addition to an assessment of the extent of drug use and kinds of drugs used by Jazz musicians and singers, the impact and costs of drug use on the lives of people in Jazz, and the changing patterns of drug use during several eras of Jazz production, the paper contextualizes drug use among Jazz performers and societal response to it in light of prevailing ethnic inequalities and critical medical anthropological theory.

  9. High dead-space syringe use among people who inject drugs in Tijuana, Mexico.

    Science.gov (United States)

    Rafful, Claudia; Zule, William; González-Zúñiga, Patricia E; Werb, Dan; Medina-Mora, María Elena; Magis-Rodriguez, Carlos; Strathdee, Steffanie A

    2015-05-01

    High dead-space syringes (HDSS) are believed to confer an elevated risk of acquiring HIV and other blood-borne infections. We identified prevalence and correlates of HDSS use among injection drug users (IDU) in Tijuana, Mexico, where syringe purchase and possession is legal without a prescription. Beginning in 2011, IDU who reported being 18 years or older and injected drugs within the last month were recruited into a prospective study. At baseline and semi-annually, 557 IDU underwent HIV-testing and interviewer-administered surveys. Logistic regression was used to identify correlates of using HDSS. Of 557 IDU, 40% had ever used HDSS, mostly because no other syringe type was available (72%), or because they were easier to get (20%). Controlling for sex and age at first injection, use of HDSS was associated with cocaine as the first drug injected (Adjusted Odds Ratio [AOR]: 2.68; Confidence Interval 95% [CI]: 1.15-6.22), having been stopped or arrested by police (AOR: 1.84; 95% CI: 1.11-3.07), being deported from the US (AOR: 1.64; 95% CI:1.06-2.53), and believing it is illegal to carry syringes (AOR:1.78; 95% CI: 1.01-3.15). Use of HDSS is surprisingly common among IDU in Tijuana. Efforts are needed to expand coverage of low-dead space syringes through existing syringe exchange programs. Education is required to increase awareness of the harms associated with HDSS, and to inform IDU that syringe possession is legal across Mexico.

  10. Entrapment of the Temporal Horn as a Cause of Pure Wernicke Aphasia: Case Report.

    Science.gov (United States)

    Spallone, Aldo; Belvisi, Daniele; Marsili, Luca

    2015-07-01

    Entrapment of the temporal horn is an extremely rare pathologic condition occurring as a result of surgery for tumors, intraventricular infections, hemorrhage, or traumatic events involving the peritrigonal area. We report a case of a 58-year-old man who presented with pure Wernicke aphasia (never described before in the albeit rare cases of isolated temporal horn dilatation) that regressed completely following successful ventriculoperitoneal shunting. The relevant literature is also briefly reviewed.

  11. Radioprotective effect of cysteamine entrapped in liposomes oraly administered to the Mouse

    International Nuclear Information System (INIS)

    Roman, Vincent; Bocquier, Francois; Leterrier, Francois; Fatome, Marc

    1982-01-01

    Cysteamine entrapped in liposomes was oraly delivered to Mice and its radioprotective effect observed as a function of the time elapsed between its administration and 60 Co gamma irradiation. A protection is manifest up to 3 hrs after administration. This result contrasts with the absence of protection afforded by cysteamine when oraly given as an aqueous solutions, and with the short lasting activity of its parenteral administration [fr

  12. Droplet Impacting on Liquid Film: Evolution of Entrapped Air Layer

    Science.gov (United States)

    Tang, Xiaoyu; Saha, Abhishek; Law, Chung K.

    2014-11-01

    In this work we experimentally studied the dynamics of droplet impacting films of various thicknesses within a range of h / R <= 1 (h: film thickness; R: droplet radius). High speed imaging and color interferometry enabled the investigation of the evolution of the air layer trapped between two surfaces, which plays a critical role in determining the collision outcome. Globally, two distinct regimes of impaction outcome, namely bouncing and merging, are observed at low and high impact inertia, respectively. Impaction with high inertia depletes the air layer before the droplet significantly deforms, resulting in permanent merging. At low impact inertia, however, color interferometry shows the existence of three phases prior to bouncing. Upon impaction, droplet endures significant deformation trapping the air layer between the interfaces, hence increasing the resistance force. This phase is characterized by fast deformation of the air film, followed by a period of pseudo equilibrium, with minimal changes in the interfacial air-film profile. The droplet also lacks kinetic energy to penetrate further into the film, resulting in a temporary balance between the droplet weight and air-film pressure. The deformed droplet eventually relaxes towards spherical shape to destroy the equilibrium. Fast change occurs in air-layer and pressure distribution favoring the droplet bouncing.

  13. Factors associated with history of drug use among female sex workers (FSW in a high HIV prevalence state of India

    Directory of Open Access Journals (Sweden)

    Medhi Gajendra

    2012-04-01

    Full Text Available Abstract Background The intersection between illicit drug use and female commercial sex work has been identified as an important factor responsible for rising HIV prevalence among female sex workers (FSW in several northeastern states of India. But, little is know about the factors associated with the use of drugs among FSWs in this region. The objective of the paper was to describe the factors associated with history of drug use among FSWs in Dimapur, an important commercial hub of Nagaland, which is a high HIV prevalence state of India. Methods FSWs were recruited using respondent driven sampling (RDS, and were interviewed to collect data on socio-demographic characteristics and HIV risk behaviours. Biological samples were tested for HIV, syphilis gonorrhea and Chlamydia. Logistic regression analysis was performed to identify factors associated with drug use. Results Among the 426 FSWs in the study, about 25% (n = 107 reported having ever used illicit drugs. Among 107 illicit drug users, 83 (77.6% were non-injecting and 24 (22.4% were injecting drug users. Drug-using FSWs were significantly more likely to test positive for one or more STIs (59% vs. 33.5%, active syphilis (27.1% vs. 11.4% and Chlamydia infection (30% vs. 19.9% compared to their non-drug using peers. Drug-using FSWs were also significantly more likely to be currently married, widowed or separated compared with non-drug-using FSWs. In multiple logistic regression analysis, being an alcohol user, being married, having a larger volume of clients, and having sexual partners who have ever used or shared injecting drugs were found to be independently associated with illicit drug use. Conclusions Drug-using FSWs were more vulnerable to STIs including HIV compared to their non-drug using peers. Several important factors associated with being an FSW who uses drugs were identified in this study and this knowledge can be used to plan more effectively targeted harm reduction strategies

  14. A targeted liposome delivery system for combretastatin A4: formulation optimization through drug loading and in vitro release studies.

    Science.gov (United States)

    Nallamothu, Ramakrishna; Wood, George C; Kiani, Mohammad F; Moore, Bob M; Horton, Frank P; Thoma, Laura A

    2006-01-01

    Efficient liposomal therapeutics require high drug loading and low leakage. The objective of this study is to develop a targeted liposome delivery system for combretastatin A4 (CA4), a novel antivascular agent, with high loading and stable drug encapsulation. Liposomes composed of hydrogenated soybean phosphatidylcholine (HSPC), cholesterol, and distearoyl phosphoethanolamine-PEG-2000 conjugate (DSPE-PEG) were prepared by the lipid film hydration and extrusion process. Cyclic arginine-glycine-aspartic acid (RGD) peptides with affinity for alphav beta3-integrins overexpressed on tumor vascular endothelial cells were coupled to the distal end of polyethylene glycol (PEG) on the liposomes sterically stabilized with PEG (non-targeted liposomes; LCLs). Effect of lipid concentration, drug-to-lipid ratio, cholesterol, and DSPE-PEG content in the formulation on CA4 loading and its release from the liposomes was studied. Total liposomal CA4 levels obtained increased with increasing lipid concentration in the formulation. As the drug-to-lipid ratio increased from 10:100 to 20:100, total drug in the liposome formulation increased from 1.05+/-0.11 mg/mL to 1.55+/-0.13 mg/mL, respectively. When the drug-to-lipid ratio was further raised to 40:100, the total drug in liposome formulation did not increase, but the amount of free drug increased significantly, thereby decreasing the percent of entrapped drug. Increasing cholesterol content in the formulation decreased drug loading. In vitro drug leakage from the liposomes increased with increase in drug-to-lipid ratio or DSPE-PEG content in the formulation; whereas increasing cholesterol content of the formulation up to 30 mol-percent, decreased CA4 leakage from the liposomes. Ligand coupling to the liposome surface increased drug leakage as a function of ligand density. Optimized liposome formulation with 100 mM lipid concentration, 20:100 drug-to-lipid ratio, 30 mol-percent cholesterol, 4 mol-percent DSPE-PEG, and 1 mol

  15. Successful retrieval of an entrapped Rotablator burr using 5 Fr guiding catheter.

    Science.gov (United States)

    Kimura, Masayoshi; Shiraishi, Jun; Kohno, Yoshio

    2011-10-01

    Although burr entrapment is a rare complication of the Rotablator, it is extremely difficult to retrieve a fixedly entrapped burr without surgical procedure. An 84-year-old male with effort angina had heavily calcified coronary trees as well as severe stenosis in the mid LCx, and moderate stenosis in the proximal LCx, and in the LMT. We planned to perform rotational atherectomy in the LCx lesions. Using 7 Fr Q-curve guiding catheter and Rotawire floppy, we began to ablate using 1.5-mm burr at 200,000 rpm. Because the burr could not pass the proximal stenosis, we exchanged the wire for Rotawire extrasupport and the burr for 1.25-mm burr, and restarted the ablation at 220,000 rpm. Although the burr could manage to pass the proximal stenosis, it had become trapped in the mid LCx lesion. Simple pull on the Rotablator, rotation of the burr, and crossing the Conquest (Confianza) wire could not retrieve it. Thus, we cut off the drive shaft and sheath of the Rotablator, inserted 5 Fr 120-cm straight guiding catheter (Heartrail ST01; Terumo) through the remaining Rotablator system, pushed the catheter tip to the lesion around the burr as well as simultaneously pulled the Rotablator, and finally could retrieve it. Then we implanted stents in the LCx and in the LMT without difficulty. The 5 Fr straight guiding catheter might be useful for retrieving an entrapped burr (1.25-mm burr). Copyright © 2011 Wiley-Liss, Inc.

  16. Efficient Calculation of Dewatered and Entrapped Areas Using Hydrodynamic Modeling and GIS

    International Nuclear Information System (INIS)

    Richmond, Marshall C.; Perkins, William A.

    2009-01-01

    River waters downstream of a hydroelectric project are often subject to rapidly changing discharge. Abrupt decreases in discharge can quickly dewater and expose some areas and isolate other areas from the main river channel, potentially stranding or entrapping fish, which often results in mortality. A methodology is described to estimate the areas dewatered or entrapped by a specific reduction in upstream discharge. A one-dimensional hydrodynamic model was used to simulate steady flows. Using flow simulation results from the model and a geographic information system (GIS), estimates of dewatered and entrapped areas were made for a wide discharge range. The methodology was applied to the Hanford Reach of the Columbia River in central Washington State. Results showed that a 280 m 3 /s discharge reduction affected the most area at discharges less than 3400 m 3 /s. At flows above 3400 m 3 /s, the affected area by a 280 m 3 /s discharge reduction (about 25 ha) was relatively constant. A 280 m 3 /s discharge reduction at lower flows affected about twice as much area. The methodology and resulting area estimates were, at the time of writing, being used to identify discharge regimes, and associated water surface elevations, that might be expected to minimize adverse impacts on juvenile fall chinook salmon (Oncorhynchus tshawytscha) that rear in the shallow near-shore areas in the Hanford Reach

  17. Wettability transition induced transformation and entrapment of polymer nanostructures in cylindrical nanopores.

    Science.gov (United States)

    Feng, Xunda; Mei, Shilin; Jin, Zhaoxia

    2011-12-06

    We apply the concept of wettability transition to manipulate the morphology and entrapment of polymer nanostructures inside cylindrical nanopores of anodic aluminum oxide (AAO) membranes. When AAO/polystyrene (PS) hybrids, i.e., AAO/PS nanorods or AAO/PS nanotubes, are immersed into a polyethylene glycol (PEG) reservoir above the glass transition temperature of PS, a wettability transition from wetting to nonwetting of PS can be triggered due to the invasion of the more wettable PEG melt. The wettability transition enables us to develop a nondestructive method to entrap hemispherically capped nanorods inside nanopores. Moreover, we can obtain single nanorods with the desired aspect ratio by further dissolving the AAO template, in contrast to the drawbacks of nonuniformity or destructiveness from the conventional ultrasonication method. In the case of AAO/PS nanotubes, the wettability transition induced dewetting of PS nanotube walls results in the disconnection and entrapment of nonwetting PS domains (i.e., nanospheres, nanocapsules, or capped nanorods). Moreover, PEG is then washed to recover the pristine wettability of PS on the alumina surface; further annealing of the PS nanospheres inside AAO nanopores under vacuum can generate some unique nanostructures, particularly semicylindrical nanorods. © 2011 American Chemical Society

  18. Optimizing the Production of Biodiesel Using Lipase Entrapped in Biomimetic Silica

    Directory of Open Access Journals (Sweden)

    Chi-Yang Yu

    2013-04-01

    Full Text Available We entrapped lipase from Pseudomonas cepacia in polyallylamine-mediated biomimetic silica, and then applied entrapped lipase to the synthesis of biodiesel with soybean oil or waste cooking oil as a feedstock. The effects of reaction temperature, substrate molar ratio (methanol/oil and n-hexane content (w/w of oil were evaluated using response surface methodology (RSM combined with Box-Behnken design. The optimal reaction conditions for soybean oil were 43.6 °C, substrate molar ratio of 4.3%, and 75% n-hexane. The predicted and experimental values of biodiesel conversion were 79% and 76%, respectively. The optimal reaction conditions for waste cooking oil were 43.3 °C, substrate molar ratio of 5%, and 38% n-hexane. The predicted and experimental values of conversion were 68% and 67%, respectively. The conversion efficiency remained the same even after 1-month storage of entrapped lipase at 4 °C or room temperature.

  19. Entrapment of cultured pancreas islets in three-dimensional collagen matrices.

    Science.gov (United States)

    Chao, S H; Peshwa, M V; Sutherland, D E; Hu, W S

    1992-01-01

    In vitro culture of islets of Langerhans decreases their immunogenicity, presumably by eliminating passenger leukocytes and other Ia+ presenting cells within the islets. Islets cultivated in petri dishes either at 37 degrees C or at 25 degrees C gradually disintegrate during culture in a time-dependent manner which is related to the free-floating condition of the islets. Also, a fraction of the islets disperse as single cells and beta-cell aggregates or adhere to the bottom of the culture dishes. Thus, the retrieval rate of transplantable islets is dampened due to their disintegration and spontaneous dispersion in conventional petri dish cultures. Entrapment of freshly harvested islets of Langerhans in a three-dimensional collagen matrix was studied as an alternative method for islet cultivation. The contraction of collagen fibrils during in vitro culture counteracts the dispersion of islets and helps in maintaining their integrity while in culture. It was observed that the entrapped islets maintain satisfactory morphology, viability, and capability of glucose-dependent insulin secretion for over 2 wk. The oxygen consumption rate and glucose metabolism of these islets was not deranged when entrapped in collagen. Also, the retrieval of islets is easier and more efficient than that observed in conventional culture systems. Our results indicate that culture of islets in three-dimensional collagen gels can potentially develop into an ideal system applicable to clinical transplantation of cultured islets or beta-cell aggregates.

  20. Entrapped cells-based-anaerobic membrane bioreactor treating domestic wastewater: Performances, fouling, and bacterial community structure.

    Science.gov (United States)

    Juntawang, Chaipon; Rongsayamanont, Chaiwat; Khan, Eakalak

    2017-11-01

    A laboratory scale study on treatment performances and fouling of entrapped cells-based-anaerobic membrane bioreactor (E-AnMBR) in comparison with suspended cells-based-bioreactor (S-AnMBR) treating domestic wastewater was conducted. The difference between E-AnMBR and S-AnMBR was the uses of cells entrapped in phosphorylated polyvinyl alcohol versus planktonic cells. Bulk organic removal efficiencies by the two AnMBRs were comparable. Lower concentrations of suspended biomass, bound extracellular polymeric substances and soluble microbial products in E-AnMBR resulted in less fouling compared to S-AnMBR. S-AnMBR provided 7 days of operation time versus 11 days for E-AnMBR before chemical cleaning was required. The less frequent chemical cleaning potentially leads to a longer membrane life-span for E-AnMBR compared to S-AnMBR. Phyla Proteobacteria, Chloroflexi, Bacteroidetes and Acidobacteria were dominant in cake sludge from both AnMBRs but their abundances were different between the two AnMBRs, suggesting influence of cell entrapment on the bacteria community. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Image findings and follow-up of lung echinococcosis after chemotherapy with liposome-entrapped albendazole

    International Nuclear Information System (INIS)

    Muhebaiti Mahesuti; Liu Wenyan; Ma Wenli; Wen Hao; Taxipulati

    2007-01-01

    Objective: To evaluate the image features of lung echinococcosis under chemotherapy with liposome-entrapped albendazole. Methods: Sixteen patients with lung echinococcosis who took orally liposome-entrapped albendazole (10 mg/kg, Bid, 3 to 10 months) were examined by X-ray film, CT or MR before therapy and followed-up by those imaging studies after therapy. The morphological changes of the lesions as reflected on imaging findings were reviewed, with correlation of the clinic check-ups and laboratory tests, to judge effectiveness of the treatment. Results: Five cases were completely cured. The treatment was effective in 6 cases, partially effective in 4 and invalid in 1 case. The imaging findings included: cavity formation in 7 cases due to hydatid cyst degeneration and absorption of cyst liquid; reduction in lesion size in 6 cases; disappearance of lesion or decrease in lesion numbers in 2 cases; increase in lesion density and blurring of cyst wall in 6 cases duo to cyst consolidation; rupture, shrinkage, collapse of cyst inner membrane in 3 cases; calcification of the cyst wall or contents in 6 cases. Conclusions: It is shown that liposome-entrapped albendazole chemotherapy has curative effect for lung echinococcosis. Imaging examinations are effective for monitoring the evolution of the disease by depicting the morphologic-pathologic changes of the lesions. (authors)

  2. Hopelessness, defeat, and entrapment in posttraumatic stress disorder: their association with suicidal behavior and severity of depression.

    Science.gov (United States)

    Panagioti, Maria; Gooding, Patricia A; Tarrier, Nicholas

    2012-08-01

    Research has shown an increased frequency of suicidal behaviors in those with PTSD, but few studies have investigated the factors that underlie the emergence of suicidal behavior in PTSD. Two theories of suicide, the Cry of Pain and the Schematic Appraisal Model of Suicide, propose that feelings of hopelessness, defeat, and entrapment are core components of suicidality. This study aimed to examine the association between suicidal behavior and hopelessness, defeat, and entrapment in trauma victims with and without a PTSD diagnosis. The results demonstrated that hopelessness, defeat, and entrapment were significantly positively associated with suicidal behavior in those with PTSD. Hopelessness and defeat were also significantly positively associated with suicidal behavior in trauma victims without PTSD. In those with PTSD, the relationship between suicidal behavior and hopelessness and entrapment remained significant after controlling for comorbid depression. The findings provide support for the contemporary theories of suicidality and have important clinical implications.

  3. Alcohol, Tobacco, and Other Drug Misuse Prevention and Cessation Programming for Alternative High School Youth: A Review

    Science.gov (United States)

    Sussman, Steve; Arriaza, Bridget; Grigsby, Timothy J.

    2014-01-01

    Background: Relative to youth in regular high schools, alternative high school (AHS) youth are at high risk for alcohol, tobacco, and other drug (ATOD) misuse. Prevention and cessation efforts are needed for this population. Methods: A systematic, exhaustive literature search was completed to identify ATOD misuse prevention and cessation research…

  4. High-throughput mapping of brain-wide activity in awake and drug-responsive vertebrates.

    Science.gov (United States)

    Lin, Xudong; Wang, Shiqi; Yu, Xudong; Liu, Zhuguo; Wang, Fei; Li, Wai Tsun; Cheng, Shuk Han; Dai, Qiuyun; Shi, Peng

    2015-02-07

    The reconstruction of neural activity across complete neural circuits, or brain activity mapping, has great potential in both fundamental and translational neuroscience research. Larval zebrafish, a vertebrate model, has recently been demonstrated to be amenable to whole brain activity mapping in behaving animals. Here we demonstrate a microfluidic array system ("Fish-Trap") that enables high-throughput mapping of brain-wide activity in awake larval zebrafish. Unlike the commonly practiced larva-processing methods using a rigid gel or a capillary tube, which are laborious and time-consuming, the hydrodynamic design of our microfluidic chip allows automatic, gel-free, and anesthetic-free processing of tens of larvae for microscopic imaging with single-cell resolution. Notably, this system provides the capability to directly couple pharmaceutical stimuli with real-time recording of neural activity in a large number of animals, and the local and global effects of pharmacoactive drugs on the nervous system can be directly visualized and evaluated by analyzing drug-induced functional perturbation within or across different brain regions. Using this technology, we tested a set of neurotoxin peptides and obtained new insights into how to exploit neurotoxin derivatives as therapeutic agents. The novel and versatile "Fish-Trap" technology can be readily unitized to study other stimulus (optical, acoustic, or physical) associated functional brain circuits using similar experimental strategies.

  5. High-performance liquid chromatographic quantification of rifampicin in human plasma: method for Therapecutic drug monitoring

    International Nuclear Information System (INIS)

    Sameh, T.; Hanene, E.; Jebali, N.

    2013-01-01

    A high performance liquid chromatography (HPLC) method has been developed that allows quantification of Rifampicin in human plasma. The method is based on the precipitation of proteins in human plasma with methanol. Optimal assay conditions were found with a C18 column and a simple mobile phase consisting of 0.05 M dipotassic hydrogen phosphate buffer and acetonitrile (53/47, V/V) with 0.086 % diethylamin, pH = 4.46. The flow-rate was 0.6 ml /mm and the drug was monitored at 340 nm. Results from the HPLC analyses showed that the assay method is linear in the concentration range of 1-40 micro g/ml, (r2 >0.99). The limit of quantification and limit of detection of Rifampicin were 0.632 micro g/ml and 0.208 micro g/ml, respectively. Intraday and interday coefficient of variation and bias were below 10% for all samples, suggesting good precision and accuracy of the method. Recoveries were greater than 90% in a plasma sample volume of 100 micro l. The method is being successfully applied to therapeutic drug monitoring of Rifapicin in plasma samples of tuberculosis and staphylococcal infections patients. (author)

  6. Determination of drug lipophilicity by phosphatidylcholine-modified microemulsion high-performance liquid chromatography.

    Science.gov (United States)

    Xuan, Xueyi; Xu, Liyuan; Li, Liangxing; Gao, Chongkai; Li, Ning

    2015-07-25

    A new biomembrane-mimetic liquid chromatographic method using a C8 stationary phase and phosphatidylcholine-modified (PC-modified) microemulsion mobile phase was used to estimate unionized and ionized drugs lipophilicity expressed as an n-octanol/water partition coefficient (logP and logD). The introduction of PC into sodium dodecyl sulfate (SDS) microemulsion yielded a good correlation between logk and logD (R(2)=0.8). The optimal composition of the PC-modified microemulsion liquid chromatography (PC-modified MELC) mobile phase was 0.2% PC-3.0% SDS-6.0% n-butanol-0.8% ethyl acetate-90.0% water (pH 7.0) for neutral and ionized molecules. The interactions between the analytes and system described by this chromatographic method is more similar to biological membrane than the n-octanol/water partition system. The result in this paper suggests that PC-modified MELC can serve as a possible alternative to the shake-flask method for high-throughput unionized and ionized drugs lipophilicity determination and simulation of biological processes. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. High risk behavior for HIV transmission among former injecting drug users: a survey from Indonesia.

    NARCIS (Netherlands)

    Iskandar, S.; Basar, D.; Hidayat, T.; Siregar, I.M.; Pinxten, W.J.L.; Crevel, R. van; Ven, A.J.A.M. van der; Jong, C.A.J. de

    2010-01-01

    BACKGROUND: Injecting drug use is an increasingly important cause of HIV transmission in most countries worldwide, especially in eastern Europe, South America, and east and southeast Asia. Among people actively injecting drugs, provision of clean needles and opioid substitution reduce

  8. High risk behavior for HIV transmission among former injecting drug users: a survey from Indonesia

    NARCIS (Netherlands)

    Iskandar, S.; Basar, D.; Hidayat, T.; Siregar, I.M.P.; Pinxten, W.J.L.; Crevel, R. van; Ven, A.J.A.M. van der; Jong, C.A.J. de

    2010-01-01

    Background: Injecting drug use is an increasingly important cause of HIV transmission in most countries worldwide, especially in eastern Europe, South America, and east and southeast Asia. Among people actively injecting drugs, provision of clean needles and opioid substitution reduce

  9. A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility.

    Directory of Open Access Journals (Sweden)

    Michael J Smout

    Full Text Available BACKGROUND: Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective high-throughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a novel application for a real-time cell monitoring device (xCELLigence that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC(50 values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and -resistant isolates of H. contortus. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing.

  10. Dual drug loaded superparamagnetic iron oxide nanoparticles for targeted cancer therapy.

    Science.gov (United States)

    Dilnawaz, Fahima; Singh, Abhalaxmi; Mohanty, Chandana; Sahoo, Sanjeeb K

    2010-05-01

    The primary inadequacy of chemotherapeutic drugs is their relative non-specificity and potential side effects to the healthy tissues. To overcome this, drug loaded multifunctional magnetic nanoparticles are conceptualized. We report here an aqueous based formulation of glycerol monooleate coated magnetic nanoparticles (GMO-MNPs) devoid of any surfactant capable of carrying high payload hydrophobic anticancer drugs. The biocompatibility was confirmed by tumor necrosis factor alpha assay, confocal microscopy. High entrapment efficiency approximately 95% and sustained release of encapsulated drugs for more than two weeks under in vitro conditions was achieved for different anticancer drugs (paclitaxel, rapamycin, alone or combination). Drug loaded GMO-MNPs did not affect the magnetization properties of the iron oxide core as confirmed by magnetization study. Additionally the MNPs were functionalized with carboxylic groups by coating with DMSA (Dimercaptosuccinic acid) for the supplementary conjugation of amines. For targeted therapy, HER2 antibody was conjugated to GMO-MNPs and showed enhanced uptake in human breast carcinoma cell line (MCF-7). The IC(50) doses revealed potential antiproliferative effect in MCF-7. Therefore, antibody conjugated GMO-MNPs could be used as potential drug carrier for the active therapeutic aspects in cancer therapy. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Mechanochemical solvent-free in situ synthesis of drug-loaded {Cu2(1,4-bdc)2(dabco)}n MOFs for controlled drug delivery

    Science.gov (United States)

    Nadizadeh, Zahra; Naimi-Jamal, M. Reza; Panahi, Leila

    2018-03-01

    In the present study, ibuprofen-loaded nano metal-organic frameworks (NMOFs) {Cu2(1,4-bdc)2(dabco)}n and {Cu2(1,4-bdc-NH2)2(dabco)}n (bdc=benzenedicarboxylic acid, and dabco=diazabicyclooctane) were synthesized by ball-milling at room temperature in 2 h. The produced drug-loaded Cu-NMOFs were studied as ibuprofen drug delivery system and exhibited well-defined drug release behavior, exceptionally high drug loading capacities and the ability to entrap the model drug. The loading efficiency for ibuprofen was determined about 50.54% and 50.27%, respectively. The drug release of NMOFs was also monitored, and all of the loaded drug was released in 1 day. The NMOFs were characterized by FT-IR spectroscopy, X-ray powder diffraction (XRPD), thermogravimetric analysis (TGA), SEM (scanning electron microscopy), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS), inductively coupled plasma (ICP), UV-vis spectroscopy and N2 adsorption porosimetry (BET&BJH).

  12. Intra-Articular Entrapment of the Medial Epicondyle following a Traumatic Fracture Dislocation of the Elbow in an Adult

    Science.gov (United States)

    Hassan, Youssef G.; Joukhadar, Nabih I.

    2018-01-01

    Medial epicondyle entrapment after an acute fracture dislocation of the elbow is a common finding in the pediatric population, but a rare finding in adults. We present a case of an adult patient diagnosed with a traumatic fracture dislocation of the elbow joint with intra-articular entrapment of the medial epicondyle. After initial evaluation, closed reduction was done. Stability testing after reduction showed an unstable joint; thus, open reduction and internal fixation was decided. PMID:29666736

  13. Popliteal vascular entrapment syndrome caused by a rare anomalous slip of the lateral head of the gastrocnemius muscle

    International Nuclear Information System (INIS)

    Liu, Patrick T.; Moyer, Adrian C.; Huettl, Eric A.; Fowl, Richard J.; Stone, William M.

    2005-01-01

    Popliteal vascular entrapment syndrome can result in calf claudication, aneurysm formation, distal arterial emboli, or popliteal vessel thrombosis. The most commonly reported causes of this syndrome have been anomalies of the medial head of the gastrocnemius muscle as it relates to the course of the popliteal artery. We report two cases of rare anomalous slips of the lateral head of the gastrocnemius muscle causing popliteal vascular entrapment syndrome. (orig.)

  14. Entrapment of 137Cs vapour generated during vitrification and casting of cesium borosilicate glass by inorganic materials

    International Nuclear Information System (INIS)

    Ram, Ramu; Gandhi, Shyamala; Dash, A.; Varma, R.N.

    2003-01-01

    Efficiency of different inorganic materials like zirconium antimonate (ZrA), ammonium molybdophosphate (AMP), synthetic zeolites, activated charcoal, glass wool etc, towards the entrapment of 137 Cs vapour escaping during vitrification and casting of cesium borosilicate glass required for the preparation of 137 Cs sources for medical and industrial applications have been determined. The recovery of entrapped cesium using dilute acids for subsequent recycling has also been explored. (author)

  15. Effect of Drug and Alcohol Education on Attitudes of High School Students.

    Science.gov (United States)

    Lignell, Constance; Davidhizar, Ruth

    1991-01-01

    Examined effects of 3-week alcohol and drug education course on attitudes about alcohol and drugs in ninth grade students (n=180). Results showed mean attitude score changed in desired direction after education indicating negative feelings toward drugs and alcohol use and abuse, polydrug use, dependency, social pressure, and media pressure and…

  16. Conical Refraction Bottle Beams for Entrapment of Absorbing Droplets.

    Science.gov (United States)

    Esseling, Michael; Alpmann, Christina; Schnelle, Jens; Meissner, Robert; Denz, Cornelia

    2018-03-22

    Conical refraction (CR) optical bottle beams for photophoretic trapping of airborne absorbing droplets are introduced and experimentally demonstrated. CR describes the circular split-up of unpolarised light propagating along an optical axis in a biaxial crystal. The diverging and converging cones lend themselves to the construction of optical bottle beams with flexible entry points. The interaction of single inkjet droplets with an open or partly open bottle beam is shown implementing high-speed video microscopy in a dual-view configuration. Perpendicular image planes are visualized on a single camera chip to characterize the integral three-dimensional movement dynamics of droplets. We demonstrate how a partly opened optical bottle transversely confines liquid objects. Furthermore we observe and analyse transverse oscillations of absorbing droplets as they hit the inner walls and simultaneously measure both transverse and axial velocity components.

  17. Biocatalytically active silCoat-composites entrapping viable Escherichia coli.

    Science.gov (United States)

    Findeisen, A; Thum, O; Ansorge-Schumacher, M B

    2014-02-01

    Application of whole cells in industrial processes requires high catalytic activity, manageability, and viability under technical conditions, which can in principle be accomplished by appropriate immobilization. Here, we report the identification of carrier material allowing exceptionally efficient adsorptive binding of Escherichia coli whole cells hosting catalytically active carbonyl reductase from Candida parapsilosis (CPCR2). With the immobilizates, composite formation with both hydrophobic and hydrophilized silicone was achieved, yielding advanced silCoat-material and HYsilCoat-material, respectively. HYsilCoat-whole cells were viable preparations with a cell loading up to 400 mg(E. coli) · g(-1)(carrier) and considerably lower leaching than native immobilizates. SilCoat-whole cells performed particularly well in neat substrate exhibiting distinctly increased catalytic activity.

  18. Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers.

    Science.gov (United States)

    de Oliveira, Carolina C; Abud, Ana Paula R; de Oliveira, Simone M; Guimarães, Fernando de S F; de Andrade, Lucas F; Di Bernardi, Raffaello P; Coletto, Ediely L de O; Kuczera, Diogo; Da Lozzo, Eneida J; Gonçalves, Jenifer P; Trindade, Edvaldo da S; Buchi, Dorly de F

    2011-10-26

    In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system. We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment. None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS)-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α) release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS), nitric oxide (NO) production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity. Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.

  19. Developments on drug discovery and on new therapeutics: highly diluted tinctures act as biological response modifiers

    Directory of Open Access Journals (Sweden)

    de Oliveira Carolina C

    2011-10-01

    Full Text Available Abstract Background In the search for new therapies novel drugs and medications are being discovered, developed and tested in laboratories. Highly diluted substances are intended to enhance immune system responses resulting in reduced frequency of various diseases, and often present no risk of serious side-effects due to its low toxicity. Over the past years our research group has been investigating the action of highly diluted substances and tinctures on cells from the immune system. Methods We have developed and tested several highly diluted tinctures and here we describe the biological activity of M1, M2, and M8 both in vitro in immune cells from mice and human, and in vivo in mice. Cytotoxicity, cytokines released and NF-κB activation were determined after in vitro treatment. Cell viability, oxidative response, lipid peroxidation, bone marrow and lymph node cells immunophenotyping were accessed after mice in vivo treatment. Results None of the highly diluted tinctures tested were cytotoxic to macrophages or K562. Lipopolysaccharide (LPS-stimulated macrophages treated with all highly diluted tinctures decreased tumour necrosis factor alpha (TNF-α release and M1, and M8 decreased IFN-γ production. M1 has decreased NF-κB activity on TNF-α stimulated reporter cell line. In vivo treatment lead to a decrease in reactive oxygen species (ROS, nitric oxide (NO production was increased by M1, and M8, and lipid peroxidation was induced by M1, and M2. All compounds enhanced the innate immunity, but M1 also augmented acquired immunity and M2 diminished B lymphocytes, responsible to acquired immunity. Conclusions Based on the results presented here, these highly diluted tinctures were shown to modulate immune responses. Even though further investigation is needed there is an indication that these highly diluted tinctures could be used as therapeutic interventions in disorders where the immune system is compromised.

  20. Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

    Science.gov (United States)

    Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

    2017-06-01

    Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving

  1. A novel high drug loading mussel-inspired polydopamine hybrid nanoparticle as a pH-sensitive vehicle for drug delivery.

    Science.gov (United States)

    Hou, Jie; Guo, Chunlei; Shi, Yuzhi; Liu, Ergang; Dong, Weibing; Yu, Bo; Liu, Shiyuan; Gong, Junbo

    2017-11-25

    A novel high drug loading pH-cleavable polymer hybrid nanoparticle was prepared via doxorubicin (DOX) grafted onto PEGylated, mussel-inspired polydopamine (PDA) and then coated onto hollow silica nanoparticles for drug delivery. A series of characterization shed light on the formation mechanisms of PDA coatings on hollow silica. We hypothesized that dopamine was first absorbed onto the surface of hollow silica and then began self-polymerization. A Dox-containing thiol moiety was fabricated with conjugation between doxorubicin hydrochloride and Mercaptopropionyalkali with a pH-cleavable hydrozone bond. Using a Michael addition reaction, several Dox-containing thiol moieties were grafted onto the surface of the PDA. The drug loading capacity can reach 35.43%. It can minimize the metabolic problem of silica. The released behavior of Dox can be significantly enhanced at endosomal pH compared to physiological pH. After folate modification, nanoparticles can lead to more cellular endocytosis. Meanwhile animal assays showed that more Dox accumulated in tumor tissue, which can enhanced the cytotoxicity to 4T1 cancer cells with a targeting group compared to free DOX and untargeted groups. Meanwhile, the tumor growth was significantly inhibited. This promising material shows a promising future as a drug delivery system. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Sol-Gel Entrapped Levonorgestrel Antibodies: Activity and Structural Changes as a Function of Different Polymer Formats

    Science.gov (United States)

    Shalev, Moran; Miriam, Altstein

    2011-01-01

    The paper describes development of a sol-gel based immunoaffinity method for the steroid hormone levonorgestrel (LNG) and the effects of changes in the sol-gel matrix format on the activity of the entrapped antibodies (Abs) and on matrix structure. The best sol-gel format for Ab entrapment was found to be a tetramethoxysilane (TMOS) based matrix at a TMOS:water ratio of 1:8, containing 10% polyethylene glycol (PEG) of MW 0.4 kDa. Addition of higher percentages of PEG or a higher MW PEG did not improve activity. No activity was obtained with a TMOS:water ratio of 1:12, most likely because of the very dense polymer that resulted from these polymerization conditions. Only minor differences in the non-specific binding were obtained with the various formats. TMOS was found to be more effective than tetrakis (2-hydroxyethyl)orthosilicate (THEOS) for entrapment of anti-levonorgestrel (LNG) Abs. However, aging the THEOS-based sol-gel for a few weeks at 4 °C stabilized the entrapped Abs and increased its binding capacity. Confocal fluorescent microscopy with fluorescein isothiocyanate (FITC) labeled immunoglobulines (IgGs) entrapped in the sol-gel matrix showed that the entrapped Abs were distributed homogenously within the gel. Scanning electron microscopy (SEM) images have shown the diverse structures of the various sol-gel formats and precursors. PMID:28880001

  3. High Throughput Screening Method for Systematic Surveillance of Drugs of Abuse by Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry.

    Science.gov (United States)

    DiBattista, Alicia; Rampersaud, Dianne; Lee, Howard; Kim, Marcus; Britz-McKibbin, Philip

    2017-11-07

    New technologies are urgently required for reliable drug screening given a worldwide epidemic of prescription drug abuse and its devastating socioeconomic impacts on public health. Primary screening of drugs of abuse (DoA) currently relies on immunoassays that are prone to bias and are not applicable to detect an alarming array of psychoactive stimulants, tranquilizers, and synthetic opioids. These limitations impact patient safety when monitoring for medication compliance, drug substitution, or misuse/abuse and require follow-up confirmatory testing by more specific yet lower throughput instrumental methods. Herein, we introduce a high throughput platform for nontargeted screening of a broad spectrum of DoA and their metabolites based on multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS). We demonstrate that MSI-CE-MS enables serial injections of 10 samples within a single run (high resolution MS with full-scan data acquisition. Unambiguous drug identification was achieved by four or more independent parameters, including comigration with a deuterated internal standard or in silico prediction of electromigration behavior together with accurate mass, most likely molecular formula, as well as MS/MS as required for confirmation testing. Acceptable precision was demonstrated for over 50 DoA at 3 concentration levels over 4 days (median coefficient of variance = 13%, n = 117) with minimal ion suppression, isobaric interferences, and sample carry-over (screening cutoff levels in human urine while allowing for systematic surveillance, specimen verification, and retrospective testing of designer drugs that elude conventional drug tests.

  4. [High activity antiretroviral therapy change associated to adverse drug reactions in a specialized center in Venezuela].

    Science.gov (United States)

    Subiela, José D; Dapena, Elida

    2016-03-01

    Adverse drug reactions (ADRs) represent the first cause of change of the first-line highly active antiretroviral therapy (HAART) regimen, therefore, they constitute the main limiting factor in the long-term follow up of HIV patients in treatment. A retrospective study was carried out in a specialized center in Lara State, Venezuela, including 99 patients over 18 years of age who had change of first-line HAART regimen due to ADRs, between 2010 and 2013. The aims of this research were to describe the sociodemographic and clinical variables, frequency of ADRs related to change of HAART, duration of the first-line HAART regimen, to determine the drugs associated with ARVs and to identify the risk factors. The ADRs constituted 47.5% of all causes of change of first-line HAART regimen, the median duration was 1.08±0.28 years. The most frequent ADRs were anemia (34.3%), hypersensitivity reactions (20.2%) and gastrointestinal intolerance (13.1%). The most frequent ARV regimen type was the protease inhibitors-based regimen (59.6%), but zidovudine was the ARV most linked to ADRs (41.4%). The regression analysis showed increased risk of ADRs in singles and students in the univariate analysis and heterosexuals and homosexuals in multivariate analysis; and decreased risk in active workers. The present work shows the high prevalence of ADRs in the studied population and represents the first case-based study that describes the pharmacoepidemiology of a cohort of HIV-positive patients treated in Venezuela.

  5. High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth

    Directory of Open Access Journals (Sweden)

    Gregory D. Bowden

    2018-04-01

    Full Text Available The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM, a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60–70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83% have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18 of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036–0.12; 95% CI] or 21.9 ng/ml [12.1–40.3; 95% CI]. These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection. Keywords: Drug repurposing, High-throughput screen, Sarcocystis neurona, Equine protozoal myeloencephalitis

  6. Physical stability, centrifugation tests, and entrapment efficiency studies of carnauba wax-decyl oleate nanoparticles used for the dispersion of inorganic sunscreens in aqueous media.

    Science.gov (United States)

    Villalobos-Hernández, J R; Müller-Goymann, C C

    2006-06-01

    Aqueous nanoscale lipid dispersions consisting of carnauba wax-decyl oleate mixtures acting as carriers or accompanying vehicles for inorganic sunscreens such as barium sulfate, strontium carbonate, and titanium dioxide were prepared by high pressure homogenization. For the manufacture of these nanosuspensions, three pigment concentrations (%wt), namely 2, 4, and 6, and two carnauba wax-decyl oleate ratios, 1:1 and 2:1, were used, being some of these combinations chosen for stability studies. Six-month physical stability tests at 4, 20, and 40 degrees C selecting the mean particle size and the polydispersity index of the nanosuspensions as reference parameters were performed. Centrifugation tests of the nanosuspensions assessed by transmission electron microscopy and by the determination of the content of pigments and carnauba wax in the separated fractions were done. The mean particle sizes and the polydispersity indices of the nanosuspensions were not altered after six-month storages at 20 and at 40 degrees C. However, the storage of those at 4 degrees C considerably increased the particle size and polydispersity of the systems, particularly when wax-oil ratios (2:1) were used for the entrapment of the pigments. Transmission electron micrographs of centrifuged samples denoted the presence of three major fractions showing the different types of particles integrated into the nanosuspensions. Furthermore, it was observed that not all the carnauba wax participated in the entrapment of the pigment. Regarding the amount of pigment being encapsulated or bonded by the wax-oil matrices, entrapment efficiencies higher than 85.52% were reported.

  7. Lithographically encoded polymer microtaggant using high-capacity and error-correctable QR code for anti-counterfeiting of drugs.

    Science.gov (United States)

    Han, Sangkwon; Bae, Hyung Jong; Kim, Junhoi; Shin, Sunghwan; Choi, Sung-Eun; Lee, Sung Hoon; Kwon, Sunghoon; Park, Wook

    2012-11-20

    A QR-coded microtaggant for the anti-counterfeiting of drugs is proposed that can provide high capacity and error-correction capability. It is fabricated lithographically in a microfluidic channel with special consideration of the island patterns in the QR Code. The microtaggant is incorporated in the drug capsule ("on-dose authentication") and can be read by a simple smartphone QR Code reader application when removed from the capsule and washed free of drug. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. The synthesis of amphipathic prodrugs of 1,2-diol drugs with saccharide conjugates by high regioselective enzymatic protocol.

    Science.gov (United States)

    Quan, Jing; Chen, Zhichun; Han, Chengyou; Lin, Xianfu

    2007-02-15

    A facile, high regioselective enzymatic synthesis approach for the preparation of amphipathic prodrugs with saccharides of mephenesin and chlorphenesin was developed. Firstly, transesterification of two drugs with divinyl dicarboxylates with different carbon chain length was performed under the catalysis of Candida antarctica lipase acrylic resin and Lipozyme in anhydrous acetone at 50 degrees C, respectively. A series of lipophilic derivatives with vinyl groups of mephenesin and chlorphenesin were prepared. The influences of different organic solvents, enzyme sources, reaction time, and the acylation reagents on the synthesis of vinyl esters were investigated. And then, protease-catalyzed high regioselective acylation of D-glucose and D-mannose with vinyl esters of mephenesin and chlorphenesin gave drug-saccharide derivatives in good yields. The studies of lipophilicity and hydrolysis in vitro of prodrugs verified that drug-saccharide derivatives had amphipathic properties, and both lipophilic and amphipathic drug derivatives had obvious controlled release characteristics.

  9. Design and characterization of sustained release ketoprofen entrapped carnauba wax microparticles.

    Science.gov (United States)

    Oliveira, Rodinelli B; Nascimento, Thais L; Lima, Eliana M

    2012-01-01

    Ketoprofen is a non-steroid anti-inflammatory drug (NSAID) used in the treatment of rheumatic diseases and in mild to moderate pain. Ketoprofen has a short biological half-life and the commercially available conventional release formulations require dosages to be administered at least 2-3 times a day. Due to these characteristics, ketoprofen is a good candidate for the preparation of controlled release formulations. In this work, a multiparticulate-sustained release dosage form containing ketoprofen in a carnauba wax matrix was developed. Particles were prepared by an emulsion congealing technique. System variables were optimized using fractional factorial and response surface experimental design. Characterization of the particles included size and morphology, flow rate, drug loading and in vitro drug release. Spherical particles were obtained with high drug load and sustained drug release profile. The optimized particles had an average diameter of approximately 200 µm, 50% (w/w) drug load, good flow properties and prolonged ketoprofen release for more than 24 h. Carnauba wax microspheres prepared in this work represent a new multiparticulate-sustained release system for the NSAID ketoprofen, exhibiting good potential for application in further pharmaceutical processes.

  10. High resolution separations of charge variants and disulfide isomers of monoclonal antibodies and antibody drug conjugates using ultra-high voltage capillary electrophoresis with high electric field strength.

    Science.gov (United States)

    Henley, W Hampton; He, Yan; Mellors, J Scott; Batz, Nicholas G; Ramsey, J Michael; Jorgenson, James W

    2017-11-10

    Ultra-high voltage capillary electrophoresis with high electric field strength has been applied to the separation of the charge variants, drug conjugates, and disulfide isomers of monoclonal antibodies. Samples composed of many closely related species are difficult to resolve and quantify using traditional analytical instrumentation. High performance instrumentation can often save considerable time and effort otherwise spent on extensive method development. Ideally, the resolution obtained for a given CE buffer system scales with the square root of the applied voltage. Currently available commercial CE instrumentation is limited to an applied voltage of approximately 30kV and a maximum electric field strength of 1kV/cm due to design limitations. The instrumentation described here is capable of safely applying potentials of at least 120kV with electric field strengths over 2000V/cm, potentially doubling the resolution of the best conventional CE buffer/capillary systems while decreasing analysis time in some applications. Separations of these complex mixtures using this new instrumentation demonstrate the potential of ultra-high voltage CE to identify the presence of previously unresolved components and to reduce analysis time for complex mixtures of antibody variants and drug conjugates. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Smart surface coating of drug nanoparticles with cross-linkable polyethylene glycol for bio-responsive and highly efficient drug delivery

    Science.gov (United States)

    Wei, Weijia; Zhang, Xiujuan; Chen, Xianfeng; Zhou, Mengjiao; Xu, Ruirui; Zhang, Xiaohong

    2016-04-01

    Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability and minimal premature release of therapeutic molecules during circulation in the blood stream. To meet this requirement, herein, we develop GSH-responsive and crosslinkable amphiphilic polyethylene glycol (PEG) molecules to modify carrier-free drug NPs. These PEG molecules can be cross-linked on the surface of the NPs to endow them with greater stability and the cross-link is sensitive to intracellular environment for bio-responsive drug release. With this elegant design, our experimental results show that the liberation of DOX from DOX-cross-linked PEG NPs is dramatically slower than that from DOX-non-cross-linked PEG NPs, and the DOX release profile can be controlled by tuning the concentration of the reducing agent to break the cross-link between PEG molecules. More importantly, in vivo studies reveal that the DOX-cross-linked PEG NPs exhibit favorable blood circulation half-life (>4 h) and intense accumulation in tumor areas, enabling effective anti-cancer therapy. We expect this work will provide a powerful strategy for stabilizing carrier-free nanomedicines and pave the way to their successful clinical applications in the future.Many drug molecules can be directly used as nanomedicine without the requirement of any inorganic or organic carriers such as silica and liposome nanostructures. This new type of carrier-free drug nanoparticles (NPs) has great potential in clinical treatment because of its ultra-high drug loading capacity and biodegradability. For practical applications, it is essential for such nanomedicine to possess robust stability

  12. Drug repurposing based on drug-drug interaction.

    Science.gov (United States)

    Zhou, Bin; Wang, Rong; Wu, Ping; Kong, De-Xin

    2015-02-01

    Given the high risk and lengthy procedure of traditional drug development, drug repurposing is gaining more and more attention. Although many types of drug information have been used to repurpose drugs, drug-drug interaction data, which imply possible physiological effects or targets of drugs, remain unexploited. In this work, similarity of drug interaction was employed to infer similarity of the physiological effects or targets for the drugs. We collected 10,835 drug-drug interactions concerning 1074 drugs, and for 700 of them, drug similarity scores based on drug interaction profiles were computed and rendered using a drug association network with 589 nodes (drugs) and 2375 edges (drug similarity scores). The 589 drugs were clustered into 98 groups with Markov Clustering Algorithm, most of which were significantly correlated with certain drug functions. This indicates that the network can be used to infer the physiological effects of drugs. Furthermore, we evaluated the ability of this drug association network to predict drug targets. The results show that the method is effective for 317 of 561 drugs that have known targets. Comparison of this method with the structure-based approach shows that they are complementary. In summary, this study demonstrates the feasibility of drug repurposing based on drug-drug interaction data. © 2014 John Wiley & Sons A/S.

  13. Sodium Chloride Crystal-Induced SERS Platform for Controlled Highly Sensitive Detection of Illicit Drugs.

    Science.gov (United States)

    Yu, Borong; Li, Pan; Zhou, Binbin; Tang, Xianghu; Li, Shaofei; Yang, Liangbao

    2018-04-03

    A sodium chloride crystal-driven spontaneous 'hot spot' structure was demonstrated as a SERS-active platform, to get reproducible SERS signals, and eliminate the need for mapping large areas, in comparison with solution phase testing. During the process of solvent evaporation, the crystals produced induced silver aggregates to assemble around themselves. The micro-scale crystals can also act as a template to obtain an optical position, such that the assembled hot area is conveniently located during SERS measurements. More importantly, the chloride ions added in colloids can also replace the citrate and on the surface of the silver sol, and further decrease the background interference. High quality SERS spectra from heroin, methamphetamine (MAMP), and cocaine have been obtained on the crystal-driven hot spot structure with high sensitivity and credible reproducibility. This approach can not only bring the nanoparticles to form plasmonic hot spots in a controlled way, and thus provide high sensitivity, but also potentially be explored as an active substrate for label-free detection of other illicit drugs or additives. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Pharmacy Students' Learning and Satisfaction With High-Fidelity Simulation to Teach Drug-Induced Dyspepsia

    Science.gov (United States)

    2013-01-01

    Objective. To assess second-year pharmacy students’ acquisition of pharmacotherapy knowledge and clinical competence from participation in a high-fidelity simulation, and to determine the impact on the simulation experience of implementing feedback from previous students. Design. A high-fidelity simulation was used to present a patient case scenario of drug-induced dyspepsia with gastrointestinal bleeding. The simulation was revised based on feedback from a previous class of students to include a smaller group size, provision of session material to students in advance, and an improved learning environment. Assessment. Student performance on pre- and post-simulation knowledge and clinical competence tests documented significant improvements in students' knowledge of dyspepsia and associated symptoms, with the greatest improvement on questions relating to the hemodynamic effects of gastrointestinal bleeding. Students were more satisfied with the simulation experience compared to students in the earlier study. Conclusion. Participation in a high-fidelity simulation allowed pharmacy students to apply knowledge and skills learned in the classroom. Improved student satisfaction with the simulation suggests that implementing feedback obtained through student course evaluations can be an effective means of improving the curriculum. PMID:23519773

  15. An analysis of respondent-driven sampling with injecting drug users in a high HIV prevalent state of India.

    Science.gov (United States)

    Phukan, Sanjib Kumar; Medhi, Gajendra Kumar; Mahanta, Jagadish; Adhikary, Rajatashuvra; Thongamba, Gay; Paranjape, Ramesh S; Akoijam, Brogen S

    2017-07-03

    Personal networks are significant social spaces to spread of HIV or other blood-borne infections among hard-to-reach population, viz., injecting drug users, female sex workers, etc. Sharing of infected needles or syringes among drug users is one of the major routes of HIV transmission in Manipur, a high HIV prevalence state in India. This study was carried out to describe the network characteristics and recruitment patterns of injecting drug users and to assess the association of personal network with injecting risky behaviors in Manipur. A total of 821 injecting drug users were recruited into the study using respondent-driven sampling (RDS) from Bishnupur and Churachandpur districts of Manipur; data on demographic characteristics, HIV risk behaviors, and network size were collected from them. Transition probability matrices and homophily indices were used to describe the network characteristics, and recruitment patterns of injecting drug users. Univariate and multivariate binary logistic regression models were performed to analyze the association between the personal networks and sharing of needles or syringes. The average network size was similar in both the districts. Recruitment analysis indicates injecting drug users were mostly engaged in mixed age group setting for injecting practice. Ever married and new injectors showed lack of in-group ties. Younger injecting drug users had mainly recruited older injecting drug users from their personal network. In logistic regression analysis, higher personal network was found to be significantly associated with increased likelihood of injecting risky behaviors. Because of mixed personal network of new injectors and higher network density associated with HIV exposure, older injecting drug users may act as a link for HIV transmission or other blood-borne infections to new injectors and also to their sexual partners. The information from this study may be useful to understanding the network pattern of injecting drug users

  16. A thermo-degradable hydrogel with light-tunable degradation and drug release.

    Science.gov (United States)

    Hu, Jingjing; Chen, Yihua; Li, Yunqi; Zhou, Zhengjie; Cheng, Yiyun

    2017-01-01

    The development of thermo-degradable hydrogels is of great importance in drug delivery. However, it still remains a huge challenge to prepare thermo-degradable hydrogels with inherent degradation, reproducible, repeated and tunable dosing. Here, we reported a thermo-degradable hydrogel that is rapidly degraded above 44 °C by a facile chemistry. Besides thermo-degradability, the hydrogel also undergoes rapid photolysis with ultraviolet light. By embedding photothermal nanoparticles or upconversion nanoparticles into the gel, it can release the entrapped cargoes such as dyes, enzymes and anticancer drugs in an on-demand and dose-tunable fashion upon near-infrared light exposure. The smart hydrogel works well both in vitro and in vivo without involving sophisticated syntheses, and is well suited for clinical cancer therapy due to the high transparency and non-invasiveness features of near-infrared light. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Dissolution and Solubility Enhancement of the Highly Lipophilic Drug Phenytoin via Interaction with Poly(N-isopropylacrylamide-co-vinylpyrrolidone) Excipients.

    Science.gov (United States)

    Widanapathirana, Lakmini; Tale, Swapnil; Reineke, Theresa M

    2015-07-06

    Excipients of natural or synthetic origin play an important role in pharmaceutical performance to enhance the solubility, bioavailability, release, and stability of insoluble drugs. Herein, a series of seven excipient models was prepared by both homopolymerization and copolymerization of 1-vinyl-2-pyrrolidone (VP) and N-isopropylacrylamide (NIPAAm) by free radical polymerization yielding two homopolymers poly(VP) and poly(NIPAAm) and five copolymers of poly(NIPAAm-co-VP) at difference compositions. While the VP monomer provided aqueous solubility at a variety of conditions to the excipient, the incorporation of NIPAAm into the copolymer offered additional hydrogen bond donating sites to optimize the drug-polymer interactions in the system. Due to the presence of NIPAAm, the copolymers were sensitive to temperature as well. It was found that as the proportion of VP was increased (from 0 to 100%), the lower critical solution temperature (LCST) and the water solubility of the polymer models increased. To examine the role of specific drug-polymer interactions during dissolution on drug solubility and bioavailability, the polymers were formulated with the anticonvulsant drug phenytoin, which is a poorly water-soluble BCS class II drug where oral absorption is limited by the drug solubility. Amorphous solid dispersions (ASD) were prepared via spray drying of phenytoin with the polymer excipient models to contain 10% and 25% by weight drug loading. Physical characterization of the ASDs by powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC) revealed that the polymers held the drug in a high-energy amorphous phase in all the formulations prepared. All ASDs exhibited improved in vitro dissolution rates compared to drug only and physical mixtures of the polymers and the drug. Drug solubility was the highest with the ASDs containing poly(NIPAAm-co-VP) 60:40 and 50:50, which showed a solubility enhancement of near 14-fold increase compared to pure drug

  18. A Critical Subset Model Provides a Conceptual Basis for the High Antiviral Activity of Major HIV Drugs**

    Science.gov (United States)

    Shen, Lin; Rabi, S. Alireza; Sedaghat, Ahmad R.; Shan, Liang; Lai, Jun; Xing, Sifei; Siliciano, Robert F.

    2012-01-01

    Control of HIV-1 replication was first achieved with regimens that included a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI); however, an explanation for the high antiviral activity of these drugs has been lacking. Indeed, conventional pharmacodynamic measures like IC50 (drug concentration causing 50% inhibition) do not differentiate NNRTIs and PIs from less active nucleoside reverse transcriptase inhibitors (NRTIs). Drug inhibitory potential depends on the slope of the dose-response curve (m), which represents how inhibition increases as a function of increasing drug concentration and is related to the Hill coefficient, a measure of intramolecular cooperativity in ligand binding to a multivalent receptor. Although NNRTIs and PIs bind univalent targets, they unexpectedly exhibit cooperative dose-response curves (m > 1). We show that this cooperative inhibition can be explained by a model in which infectivity requires participation of multiple copies of a drug target in an individual life cycle stage. A critical subset of these target molecules must be in the unbound state. Consistent with experimental observations, this model predicts m > 1 for NNRTIs and PIs and m = 1 in situations where a single drug target/virus mediates a step in the life cycle, as is the case with NRTIs and integrase strand transfer inhibitors. This model was tested experimentally by modulating the number of functional drug targets per virus, and dose-response curves for modulated virus populations fit model predictions. This model explains the high antiviral activity of two drug classes important for successful HIV-1 treatment and defines a characteristic of good targets for antiviral drugs in general, namely, intermolecular cooperativity. PMID:21753122

  19. High Levels of Transmitted HIV Drug Resistance in a Study in Papua New Guinea.

    Science.gov (United States)

    Lavu, Evelyn; Kave, Ellan; Mosoro, Euodia; Markby, Jessica; Aleksic, Eman; Gare, Janet; Elsum, Imogen A; Nano, Gideon; Kaima, Petronia; Dala, Nick; Gurung, Anup; Bertagnolio, Silvia; Crowe, Suzanne M; Myatt, Mark; Hearps, Anna C; Jordan, Michael R

    2017-01-01

    Papua New Guinea is a Pacific Island nation of 7.3 million people with an estimated HIV prevalence of 0.8%. ART initiation and monitoring are guided by clinical staging and CD4 cell counts, when available. Little is known about levels of transmitted HIV drug resistance in recently infected individuals in Papua New Guinea. Surveillance of transmitted HIV drug resistance in a total of 123 individuals recently infected with HIV and aged less than 30 years was implemented in Port Moresby (n = 62) and Mount Hagen (n = 61) during the period May 2013-April 2014. HIV drug resistance testing was performed using dried blood spots. Transmitted HIV drug resistance was defined by the presence of one or more drug resistance mutations as defined by the World Health Organization surveillance drug resistance mutations list. The prevalence of non-nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 16.1% (95% CI 8.8%-27.4%) and 8.2% (95% CI 3.2%-18.2%) in Port Moresby and Mount Hagen, respectively. The prevalence of nucleoside reverse transcriptase inhibitor transmitted HIV drug resistance was 3.2% (95% CI 0.2%-11.7%) and 3.3% (95% CI 0.2%-11.8%) in Port Moresby and Mount Hagen, respectively. No protease inhibitor transmitted HIV drug resistance was observed. The level of non-nucleoside reverse transcriptase inhibitor drug resistance in antiretroviral drug naïve individuals recently infected with HIV in Port Moresby is amongst the highest reported globally. This alarming level of transmitted HIV drug resistance in a young sexually active population threatens to limit the on-going effective use of NNRTIs as a component of first-line ART in Papua New Guinea. To support the choice of nationally recommended first-line antiretroviral therapy, representative surveillance of HIV drug resistance among antiretroviral therapy initiators in Papua New Guinea should be urgently implemented.

  20. High risk behaviors of injection drug users registered with harm reduction programme in Karachi, Pakistan

    Directory of Open Access Journals (Sweden)

    Memon Ashraf

    2007-02-01

    Full Text Available Abstract Background Surveillance data of Sindh AIDS Control Programme, Pakistan suggest that HIV infection is rapidly increasing among IDUs in Karachi and has reached 9% in 2004–5 indicating that the country has progressed from nascent to concentrated level of HIV epidemic. Findings of 2nd generation surveillance in 2004–5 also indicate 104/395 (26.3% IDUs HIV positive in the city. Methods We conducted a cross sectional study among registered IDUs of a needle exchange and harm reduction programme in Karachi, Pakistan. A total of 161 IDUs were included in the study between October–November 2003. A detailed questionnaire was implemented and blood samples were collected for HIV, hepatitis B & C and syphilis. HIV, hepatitis B and C antibody tests were performed using Enzyme Linked Immunosorbent Assay (ELISA method. Syphilis tests (RPR & TPHA were performed on Randox kit. Besides calculating frequencies univariate analysis was performed using t tests for continuous variables as age, age at first intercourse and average age of initiation of addiction and chi square for categorical variables like paid for sex or not to identify risk factors for hepatitis B and C and syphilis. Results Average age of IDU was 35.9 years and average age of initiation of drugs was 15.9 years. Number of drug injections per day was 2.3. Shooting drugs in group sharing syringes was reported by 128 (79.5% IDUs. Over half 94 (58.3% reported paying for sex and 64% reported never using a condom. Commercial selling of blood was reported by 44 (28%. 1 of 161 was HIV positive (0.6%. The prevalence of hepatitis B was 12 (7.5%, hepatitis C 151 (94.3% and syphilis 21 (13.1%. IDUs who were hepatitis C positive were more likely to start sexual activity at an earlier age and had never used condoms. Similarly IDUs who were hepatitis B positive were more likely to belong to a younger age group. Syphilis positive IDUs were more likely to have paid for sex and had never used a condom

  1. Convective transport of highly plasma protein bound drugs facilitates direct penetration into deep tissues after topical application

    Science.gov (United States)

    Dancik, Yuri; Anissimov, Yuri G; Jepps, Owen G; Roberts, Michael S

    2012-01-01

    AIMS To relate the varying dermal, subcutaneous and muscle microdialysate concentrations found in man after topical application to the nature of the drug applied and to the underlying physiology. METHODS We developed a physiologically based pharmacokinetic model in which transport to deeper tissues was determined by tissue diffusion, blood, lymphatic and intersitial flow transport and drug properties. The model was applied to interpret published human microdialysis data, estimated in vitro dermal diffusion and protein binding affinity of drugs that have been previously applied topically in vivo and measured in deep cutaneous tissues over time. RESULTS Deeper tissue microdialysis concentrations for various drugs in vivo vary widely. Here, we show that carriage by the blood to the deeper tissues below topical application sites facilitates the transport of highly plasma protein bound drugs that penetrate the skin, leading to rapid and significant concentrations in those tissues. Hence, the fractional concentration for the highly plasma protein bound diclofenac in deeper tissues is 0.79 times that in a probe 4.5 mm below a superficial probe whereas the corresponding fractional concentration for the poorly protein bound nicotine is 0.02. Their corresponding estimated in vivo lag times for appearance of the drugs in the deeper probes were 1.1 min for diclofenac and 30 min for nicotine. CONCLUSIONS Poorly plasma protein bound drugs are mainly transported to deeper tissues after topical application by tissue diffusion whereas the transport of highly plasma protein bound drugs is additionally facilitated by convective blood, lymphatic and interstitial transport to deep tissues. PMID:21999217

  2. High Throughput Screening in Duchenne Muscular Dystrophy: From Drug Discovery to Functional Genomics

    Directory of Open Access Journals (Sweden)

    Thomas J.J. Gintjee

    2014-11-01

    Full Text Available Centers for the screening of biologically active compounds and genomic libraries are becoming common in the academic setting and have enabled researchers devoted to developing strategies for the treatment of diseases or interested in studying a biological phenomenon to have unprecedented access to libraries that, until few years ago, were accessible only by pharmaceutical companies. As a result, new drugs and genetic targets have now been identified for the treatment of Duchenne muscular dystrophy (DMD, the most prominent of the neuromuscular disorders affecting children. Although the work is still at an early stage, the results obtained to date are encouraging and demonstrate the importance that these centers may have in advancing therapeutic strategies for DMD as well as other diseases. This review will provide a summary of the status and progress made toward the development of a cure for this disorder and implementing high-throughput screening (HTS technologies as the main source of discovery. As more academic institutions are gaining access to HTS as a valuable discovery tool, the identification of new biologically active molecules is likely to grow larger. In addition, the presence in the academic setting of experts in different aspects of the disease will offer the opportunity to develop novel assays capable of identifying new targets to be pursued as potential therapeutic options. These assays will represent an excellent source to be used by pharmaceutical companies for the screening of larger libraries providing the opportunity to establish strong collaborations between the private and academic sectors and maximizing the chances of bringing into the clinic new drugs for the treatment of DMD.

  3. High throughput screening in duchenne muscular dystrophy: from drug discovery to functional genomics.

    Science.gov (United States)

    Gintjee, Thomas J J; Magh, Alvin S H; Bertoni, Carmen

    2014-11-14

    Centers for the screening of biologically active compounds and genomic libraries are becoming common in the academic setting and have enabled researchers devoted to developing strategies for the treatment of diseases or interested in studying a biological phenomenon to have unprecedented access to libraries that, until few years ago, were accessible only by pharmaceutical companies. As a result, new drugs and genetic targets have now been identified for the treatment of Duchenne muscular dystrophy (DMD), the most prominent of the neuromuscular disorders affecting children. Although the work is still at an early stage, the results obtained to date are encouraging and demonstrate the importance that these centers may have in advancing therapeutic strategies for DMD as well as other diseases. This review will provide a summary of the status and progress made toward the development of a cure for this disorder and implementing high-throughput screening (HTS) technologies as the main source of discovery. As more academic institutions are gaining access to HTS as a valuable discovery tool, the identification of new biologically active molecules is likely to grow larger. In addition, the presence in the academic setting of experts in different aspects of the disease will offer the opportunity to develop novel assays capable of identifying new targets to be pursued as potential therapeutic options. These assays will represent an excellent source to be used by pharmaceutical companies for the screening of larger libraries providing the opportunity to establish strong collaborations between the private and academic sectors and maximizing the chances of bringing into the clinic new drugs for the treatment of DMD.

  4. Low and High Frequency Hippocampal Stimulation for Drug-Resistant Mesial Temporal Lobe Epilepsy.

    Science.gov (United States)

    Lim, Siew-Na; Lee, Ching-Yi; Lee, Shih-Tseng; Tu, Po-Hsun; Chang, Bao-Luen; Lee, Chih-Hong; Cheng, Mei-Yun; Chang, Chun-Wei; Tseng, Wei-En Johnny; Hsieh, Hsiang-Yao; Chiang, Hsing-I; Wu, Tony

    2016-06-01

    Electrical stimulation of the hippocampus offers the possibility to treat patients with mesial temporal lobe epilepsy (MTLE) who are not surgical candidates. We report long-term follow-up results in five patients receiving low or high frequency hippocampal stimulation for drug-resistant MTLE. The patients underwent stereotactic implantation of quadripolar stimulating electrodes in the hippocampus. Two of the patients received unilateral electrode implantation, while the other three received bilateral implantation. Stimulation of the hippocampal electrodes was turned ON immediately after the implantation of an implantable pulse generator, with initial stimulation parameters: 1 V, 90-150 μs, 5 or 145 Hz. The frequency of seizures was monitored and compared with preimplantation baseline data. Two men and three women, aged 27-61 years were studied, with a mean follow-up period of 38.4 months (range, 30-42 months). The baseline seizure frequency was 2.0-15.3/month. The five patients had an average 45% (range 22-72%) reduction in the frequency of seizures after hippocampal stimulation over the study period. Low frequency hippocampal stimulation decreased the frequency of seizures in two patients (by 54% and 72%, respectively). No implantation- or stimulation-related side effects were reported. Electrical stimulation of the hippocampus is a minimally invasive and reversible method that can improve seizure outcomes in patients with drug-resistant MTLE. The optimal frequency of stimulation varied from patient to patient and therefore required individual setting. These experimental results warrant further controlled studies with a large patient population to evaluate the long-term effect of hippocampal stimulation with different stimulation parameters. © 2016 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals, Inc. on behalf of International Neuromodulation Society.

  5. High prevalence of latent tuberculosis infection among injection drug users in Tijuana, Mexico.

    Science.gov (United States)

    Garfein, R S; Lozada, R; Liu, L; Laniado-Laborin, R; Rodwell, T C; Deiss, R; Alvelais, J; Catanzaro, A; Chiles, P G; Strathdee, S A

    2009-05-01

    We studied prevalence and correlates of latent tuberculosis infection (LTBI) among injection drug users (IDUs) in Tijuana, Mexico, where tuberculosis (TB) is endemic. IDUs aged > or =18 years were recruited via respondent-driven sampling (RDS) and underwent standardized interviews, human immunodeficiency virus (HIV) antibody testing and LTBI screening using Quanti-FERON((R))-TB Gold In-Tube, a whole-blood interferon-gamma release assay (IGRA). LTBI prevalence was estimated and correlates were identified using RDS-weighted logistic regression. Of 1020 IDUs, 681 (67%) tested IGRA-positive and 44 (4%) tested HIV-positive. Mean age was 37 years, 88% were male and 98% were Mexican-born. IGRA positivity was associated with recruitment nearest the US border (aOR 1.64, 95%CI 1.09-2.48), increasing years of injection (aOR 1.20/5 years, 95%CI 1.07-1.34), and years lived in Tijuana (aOR 1.10/5 years, 95%CI 1.03-1.18). Speaking some English (aOR 0.38, 95%CI 0.25-0.57) and injecting most often at home in the past 6 months (aOR 0.68, 95%CI 0.45-0.99) were inversely associated with IGRA positivity. Increased LTBI prevalence among IDUs in Tijuana appears to be associated with greater drug involvement. Given the high risk for HIV infection among Tijuana's IDUs, interventions are urgently needed to prevent HIV infection and treat LTBI among IDUs before these epidemics collide.

  6. A treatment plant receiving waste water from multiple bulk drug manufacturers is a reservoir for highly multi-drug resistant integron-bearing bacteria.

    Directory of Open Access Journals (Sweden)

    Nachiket P Marathe

    Full Text Available The arenas and detailed mechanisms for transfer of antibiotic resistance genes between environmental bacteria and pathogens are largely unclear. Selection pressures from antibiotics in situations where environmental bacteria and human pathogens meet are expected to increase the risks for such gene transfer events. We hypothesize that waste-water treatment plants (WWTPs serving antibiotic manufacturing industries may provide such spawning grounds, given the high bacterial densities present there together with exceptionally strong and persistent selection pressures from the antibiotic-contaminated waste. Previous analyses of effluent from an Indian industrial WWTP that processes waste from bulk drug production revealed the presence of a range of drugs, including broad spectrum antibiotics at extremely high concentrations (mg/L range. In this study, we have characterized the antibiotic resistance profiles of 93 bacterial strains sampled at different stages of the treatment process from the WWTP against 39 antibiotics belonging to 12 different classes. A large majority (86% of the strains were resistant to 20 or more antibiotics. Although there were no classically-recognized human pathogens among the 93 isolated strains, opportunistic pathogens such as Ochrobactrum intermedium, Providencia rettgeri, vancomycin resistant Enterococci (VRE, Aerococcus sp. and Citrobacter freundii were found to be highly resistant. One of the O. intermedium strains (ER1 was resistant to 36 antibiotics, while P. rettgeri (OSR3 was resistant to 35 antibiotics. Class 1 and 2 integrons were detected in 74/93 (80% strains each, and 88/93 (95% strains harbored at least one type of integron. The qPCR analysis of community DNA also showed an unprecedented high prevalence of integrons, suggesting that the bacteria living under such high selective pressure have an appreciable potential for genetic exchange of resistance genes via mobile gene cassettes. The present study provides

  7. Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

    OpenAIRE

    Burkhart, Keith K.; Abernethy, Darrell; Jackson, David

    2015-01-01

    Drug features that are associated with Stevens-Johnson syndrome (SJS) have not been fully characterized. A molecular target analysis of the drugs associated with SJS in the FDA Adverse Event Reporting System (FAERS) may contribute to mechanistic insights into SJS pathophysiology. The publicly available version of FAERS was analyzed to identify disproportionality among the molecular targets, metabolizing enzymes, and transporters for drugs associated with SJS. The FAERS in-house version was al...

  8. Update on pediatric resuscitation drugs: high dose, low dose, or no dose at all.

    Science.gov (United States)

    Sorrentino, Annalise

    2005-04-01

    Pediatric resuscitation has been a topic of discussion for years. It is difficult to keep abreast of changing recommendations, especially for busy pediatricians who do not regularly use these skills. This review will focus on the most recent guidelines for resuscitation drugs. Three specific questions will be discussed: standard dose versus high-dose epinephrine, amiodarone use, and the future of vasopressin in pediatric resuscitation. The issue of using high-dose epinephrine for cardiopulmonary resuscitation refractory to standard dose epinephrine has been a topic of debate for many years. Recently, a prospective, double-blinded study was performed to help settle the debate. These results will be reviewed and compared with previous studies. Amiodarone is a medication that was added to the pediatric resuscitation algorithms with the most recent recommendations from the American Heart Association in 2000. Its use and safety will also be discussed. Another topic that is resurfacing in resuscitation is the use of vasopressin. Its mechanism and comparisons to other agents will be highlighted, although its use in the pediatric patient has not been thoroughly studied. Pediatric resuscitation is a constantly evolving subject that is on the mind of anyone taking care of sick children. Clinicians are continually searching for the most effective methods to resuscitate children in terms of short- and long-term outcomes. It is important to be familiar with not only the agents being used but also the optimal way to use them.

  9. An In Vivo Platform for Rapid High-Throughput Antitubercular Drug Discovery

    Directory of Open Access Journals (Sweden)

    Kevin Takaki

    2012-07-01

    Full Text Available Treatment of tuberculosis, like other infectious diseases, is increasingly hindered by the emergence of drug resistance. Drug discovery efforts would be facilitated by facile screening tools that incorporate the complexities of human disease. Mycobacterium marinum-infected zebrafish larvae recapitulate key aspects of tuberculosis pathogenesis and drug treatment. Here, we develop a model for rapid in vivo drug screening using fluorescence-based methods for serial quantitative assessment of drug efficacy and toxicity. We provide proof-of-concept that both traditional bacterial-targeting antitubercular drugs and newly identified host-targeting drugs would be discovered through the use of this model. We demonstrate the model’s utility for the identification of synergistic combinations of antibacterial drugs and demonstrate synergy between bacterial- and host-targeting compounds. Thus, the platform can be used to identify new antibacterial agents and entirely new classes of drugs that thwart infection by targeting host pathways. The methods developed here should be widely applicable to small-molecule screens for other infectious and noninfectious diseases.

  10. A high-speed drug interaction search system for ease of use in the clinical environment.

    Science.gov (United States)

    Takada, Masahiro; Inada, Hiroshi; Nakazawa, Kazuo; Tani, Shoko; Iwata, Michiaki; Sugimoto, Yoshihisa; Nagata, Satoru

    2012-12-01

    With the advancement of pharmaceutical development, drug interactions have become increasingly complex. As a result, a computer-based drug interaction search system is required to organize the whole of drug interaction data. To overcome problems faced with the existing systems, we developed a drug interaction search system using a hash table, which offers higher processing speeds and easier maintenance operations compared with relational databases (RDB). In order to compare the performance of our system and MySQL RDB in terms of search speed, drug interaction searches were repeated for all 45 possible combinations of two out of a group of 10 drugs for two cases: 5,604 and 56,040 drug interaction data. As the principal result, our system was able to process the search approximately 19 times faster than the system using the MySQL RDB. Our system also has several other merits such as that drug interaction data can be created in comma-separated value (CSV) format, thereby facilitating data maintenance. Although our system uses the well-known method of a hash table, it is expected to resolve problems common to existing systems and to be an effective system that enables the safe management of drugs.

  11. Photoimages and the release characteristics of lipophilic matrix tablets containing highly water-soluble potassium citrate with high drug loadings.

    Science.gov (United States)

    Cao, Qing-Ri; Kim, Tae-Wan; Lee, Beom-Jin

    2007-07-18

    Two types of the carnauba wax-based lipophilic matrix tablet using spray-dried granules (SDT) or directly compressible powdered mixtures (DCT) were prepared for sustained release. The model drug was a highly water-soluble potassium citrate and loaded about 74% of the total tablet weight. The SDT slowly eroded and disintegrated during the release study without showing sustained release when the hydrophilic excipients were added. In contrast, the DCT was more efficient for sustained release. The release rate decreased with increasing carnauba wax concentration. In particular, the sustained release rate was markedly pronounced when the lipophilic stearyl alcohol and stearic acid were combined with the carnauba wax. The surface of the intact DCT appeared to be smooth and rusty. The DCT rose to the surface from the bottom of the vessel during the release test, and numerous pores and cracks with no signs of disintegration were also observed after the release test. The release profile was dependent on the formulation composition and preparation method of the matrix tablet. Diffusion-controlled leaching through the channels of the pores and cracks of the lipophilic matrix tablet (DCT) is a key to the sustained release.

  12. Insights into the swelling process and drug release mechanisms from cross-linked pectin/high amylose starch matrices

    Directory of Open Access Journals (Sweden)

    Fernanda M. Carbinatto

    2014-02-01

    Full Text Available Cross-linked pectin/high amylose mixtures were evaluated as a new excipient for matrix tablets formulations, since the mixing of polymers and cross-linking reaction represent rational tools to reach materials with modulated and specific properties that meet specific therapeutic needs. Objective: In this work the influence of polymer ratio and cross-linking process on the swelling and the mechanism driving the drug release from swellable matrix tablets prepared with this excipient was investigated. Methods: Cross-linked samples were characterized by their micromeritic properties (size and shape, density, angle of repose and flow rate and liquid uptake ability. Matrix tablets were evaluated according their physical properties and the drug release rates and mechanisms were also investigated. Results: Cross-linked samples demonstrated size homogeneity and irregular shape, with liquid uptake ability insensible to pH. Cross-linking process of samples allowed the control of drug release rates and the drug release mechanism was influenced by both polymer ratio and cross-linking process. The drug release of samples with minor proportion of pectin was driven by an anomalous transport and the increase of the pectin proportion contributed to the erosion of the matrix. Conclusion: The cross-linked mixtures of high amylose and pectin showed a suitable excipient for slowing the drug release rates.

  13. A continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs.

    Science.gov (United States)

    Dong, Yuancai; Ng, Wai Kiong; Hu, Jun; Shen, Shoucang; Tan, Reginald B H

    2010-02-15

    Rapid and homogeneous mixing of the solvent and antisolvent is critical to achieve submicron drug particles by antisolvent precipitation technique. This work aims to develop a continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs with spironolactone as a model drug. Continuous antisolvent production of drug nanoparticles was carried out with a SMV DN25 static mixer comprising 6-18 mixing elements. The total flow rate ranged from 1.0 to 3.0 L/min while the flow rate ratio of solvent to antisolvent was maintained at 1:9. It is found that only 6 mixing elements were sufficient to precipitate the particles in the submicron range. Increasing the number of elements would further reduce the precipitated particle size. Increasing flow rate from 1.0 to 3.0 L/min did not further reduce the particle size, while higher drug concentrations led to particle size increase. XRD and SEM results demonstrated that the freshly precipitated drug nanoparticles are in the amorphous state, which would, in presence of the mixture of solvent and antisolvent, change to crystalline form in short time. The lyophilized spironolactone nanoparticles with lactose as lyoprotectant possessed good redispersibility and showed 6.6 and 3.3 times faster dissolution rate than that of lyophilized raw drug formulation in 5 and 10 min, respectively. The developed static mixing process exhibits high potential for continuous and large-scale antisolvent precipitation of submicron drug particles. Copyright 2009 Elsevier B.V. All rights reserved.

  14. Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery

    Directory of Open Access Journals (Sweden)

    Naren Subbiah

    2017-01-01

    Full Text Available Phospholipid-based deformable nanovesicles (DNVs that have flexibility in shape offer an adaptable and facile method to encapsulate diverse classes of therapeutics and facilitate localized transdermal delivery while minimizing systemic exposure. Here we report the use of a microfluidic reactor for the synthesis of DNVs and show that alteration of input parameters such as flow speeds as well as molar and flow rate ratios increases entrapment efficiency of drugs and allows fine-tuning of DNV size, elasticity, and surface charge. To determine the ability of DNV-encapsulated drug to be delivered transdermally to a local site, we synthesized, characterized, and tested DNVs carrying the fluorescently labeled hydrophilic bisphosphonate drug AF-647 zoledronate (AF647-Zol. AF647-Zol DNVs were lyophilized, resuspended, and applied topically as a paste to the calvarial skin of mice. High-resolution fluorescent imaging and confocal microscopy revealed significant increase of encapsulated payload delivery to the target tissue—cranial bone—by DNVs as compared to nondeformable nanovesicles (NVs or aqueous drug solutions. Interestingly, NV delivery was not superior to aqueous drug solution. Our studies show that microfluidic reactor-synthesized DNVs can be produced in good yield, with high encapsulation efficiency, reproducibility, and stability after storage, and represent a useful vehicle for localized transdermal drug delivery.

  15. Intranasal administration of carbamazepine-loaded carboxymethyl chitosan nanoparticles for drug delivery to the brain

    Directory of Open Access Journals (Sweden)

    Shanshan Liu

    2018-01-01

    Full Text Available Epilepsy is considered as a common and diverse set of chronic neurological disorders and its symptoms can be controlled by antiepileptic drugs (AEDs. The presence of p-glycoprotein and multi-drug resistance transporters in the blood-brain barrier could prevent the entry of AEDs into the brain, causing drug resistant epilepsy. To overcome this problem, we propose using carboxymethyl chitosan nanoparticles as a carrier to deliver carbamazepine (CBZ intra-nasally with the purpose to bypass the blood-brain barrier thus to enhance the brain drug concentration and the treatment efficacy. Results so far indicate that the developed CBZ-NPs have small particle size (218.76 ± 2.41 nm with high drug loading (around 35% and high entrapment efficiency (around 80%. The in vitro release profiles of CBZ from the NPs are in accordance with the Korsmeyer-peppas model. The in vivo results show that both encapsulation of CBZ in nanoparticles and the nasal route determined the enhancement of the drug bioavailability and brain targeting characteristics.

  16. Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening

    Directory of Open Access Journals (Sweden)

    Pothineni VR

    2016-04-01

    Full Text Available Venkata Raveendra Pothineni,1 Dhananjay Wagh,1 Mustafeez Mujtaba Babar,1 Mohammed Inayathullah,1 David Solow-Cordero,2 Kwang-Min Kim,1 Aneesh V Samineni,1 Mansi B Parekh,1 Lobat Tayebi,3 Jayakumar Rajadas1 1Biomaterials and Advanced Drug Delivery Laboratory, Stanford Cardiovascular Pharmacology Division, Cardiovascular Institute, Stanford University School of Medicine, Palo Alto, 2Chemical & Systems Biology, Stanford University School of Medicine, Stanford, CA, 3Department of Developmental Sciences, Marquette University School of Dentistry, Milwaukee, WI, USA Abstract: Lyme disease is the most common zoonotic bacterial disease in North America. It is estimated that >300,000 cases per annum are reported in USA alone. A total of 10%–20% of patients who have been treated with antibiotic therapy report the recrudescence of symptoms, such as muscle and joint pain, psychosocial and cognitive difficulties, and generalized fatigue. This condition is referred to as posttreatment Lyme disease syndrome. While there is no evidence for the presence of viable infectious organisms in individuals with posttreatment Lyme disease syndrome, some researchers found surviving Borrelia burgdorferi population in rodents and primates even after antibiotic treatment. Although such observations need more ratification, there is unmet need for developing the therapeutic agents that focus on removing the persisting bacterial form of B. burgdorferi in rodent and nonhuman primates. For this purpose, high-throughput screening was done using BacTiter-Glo assay for four compound libraries to identify candidates that stop the growth of B. burgdorferi in vitro. The four chemical libraries containing 4,366 compounds (80% Food and Drug Administration [FDA] approved that were screened are Library of Pharmacologically Active Compounds (LOPAC1280, the National Institutes of Health Clinical Collection, the Microsource Spectrum, and the Biomol FDA. We subsequently identified 150

  17. Delta-sleep inducing peptide entrapment in the charged macroporous matrices

    International Nuclear Information System (INIS)

    Sukhanova, Tatiana V.; Artyukhov, Alexander A.; Gurevich, Yakov M.; Semenikhina, Marina A.; Prudchenko, Igor A.; Shtilman, Mikhail I.; Markvicheva, Elena A.

    2014-01-01

    Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2–6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process. - Graphical abstract: Delta-sleep inducing peptide possessing neuroprotective and wound healing properties was adsorbed on positively charged polymer matrix Co-DMAEMA-MBAA for tissue engineering. The peptide released from Co-DMAEMA-MBAA matrix in function of ionic strength of solution, pH decreasing stimulated peptide release from Co-DMAEMA-MBAA matrix for 3 h. This construction could be a base of new bioactive implants. - Highlights: • Macroporous positively charged Co-DMAEMA-MBAA matrix pore size was 20–35 μm. • DSIP was adsorbed on Co-DMAEMA-MBAA totally in 16 h. • Its release depends on ionic strength of solution (no release in 25% ethanol or water). • Co-DMAEMA-MBAA matrix swelling depends on pH and ionic strength of solution. • DSIP is destroyed in PBS and 0.9% NaCl in 5 days, but in water it was more stable

  18. Co-contamination of Cu and Cd in paddy fields: Using periphyton to entrap heavy metals

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jiali [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Sciences, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing 210008 (China); College of Resource and Environment, University of Chinese Academy of Sciences, Beijing 100049 (China); Tang, Cilai [Department of Environmental Engineering, College of Hydraulic & Environmental Engineering, China Three Gorges University, Yichang 443002 (China); Wang, Fengwu [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Sciences, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing 210008 (China); School of Civil Engineering, East China Jiaotong University, 808 Shuang Gang East Road, Nanchang, Jiangxi 330013 (China); Wu, Yonghong, E-mail: yhwu@issas.ac.cn [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Sciences, Chinese Academy of Sciences, 71 East Beijing Road, Nanjing 210008 (China)

    2016-03-05

    Highlights: • Periphyton was capable of simultaneously entrapping Cu and Cd from paddy fields. • Cu and Cd bioavailability decreased with time after exposure to periphyton. • Periodic adsorption–desorption was the main mechanism used to remove Cd and Cu. • Periphyton was able to adapt to steady accumulation of Cu and Cd. • The inclusion of periphyton will help entrap heavy metals in paddy fields. - Abstract: The ubiquitous native periphyton was used to entrap Cu and Cd from paddy fields. Results showed that Cu- and Cd-hydrate species such as CuOH{sup +}, Cu{sub 2}(OH){sub 2}{sup 2+}, CdOH{sup +}, and Cu{sub 3}(OH){sub 4}{sup 2+} decreased with time in the presence of periphyton. When the initial concentrations of Cu and Cd were 10 mg/L, the heavy metal content in the periphyton fluctuated from 145.20 mg/kg to 342.42 mg/kg for Cu and from 101.75 mg/kg to 236.29 mg/kg for Cd after 2 h exposure. The concentration of Cd in periphytic cells varied from 42.93 mg/kg to 174 mg/kg after 2 h. The dominant periphyton microorganism species shifted from photoautotrophs to heterotrophs during the exposure of periphyton to Cu and Cd co-contamination. Although Cu and Cd could inhibit periphyton photosynthesis and carbon utilization, the periphyton was able to adapt to the test conditions. Cu and Cd accumulation in rice markedly decreased in the presence of periphyton while the number of rice seeds germinating was higher in the periphyton treatments. These results suggest that the inclusion of native periphyton in paddy fields provides a promising buffer to minimize the effects of Cu and Cd pollution on rice growth and food safety.

  19. Minimally invasive percutaneous management of large bladder stones with a laparoscopic entrapment bag.

    Science.gov (United States)

    Tan, Yung K; Gupta, Dilan M; Weinberg, Aaron; Matteis, August J; Kotwal, Sunny; Gupta, Mantu

    2014-01-01

    The treatment of large volume bladder stones is a management conundrum. Transurethral methods are plagued by long operative times, trauma to the bladder mucosa, and the need for a postoperative urethral catheter. Open cystolithotomy has higher morbidity. We present the percutaneous management of bladder stones with the novel use of a laparoscopic entrapment bag. Twenty-five patients (mean age 65.7), including 22 men and 3 women, 4 with a neurogenic bladder and 21 with a prior diagnosis of benign prostatic hyperplasia, underwent our novel technique. The mean number of stones was 6.8±8.0 (range, 1 to 30) and total stone burden 10.4±10.5 cm (range, 3.0 to 50.0 cm). Using regional or general anesthesia and flexible cystoscopic guidance, percutaneous bladder access was achieved. The tract was balloon dilated to 30F and stones captured in a laparoscopic entrapment bag. The bag's opening was exteriorized and stone fragmentation and comminution were achieved using a nephroscope and pneumatic or ultrasonic lithotripters. The bag was extracted and a 22F suprapubic catheter was inserted into the bladder; the patient was discharged the next day after a voiding trial. The procedure was done without fluoroscopy. No foley catheter was necessary. All patients were rendered stone free. The mean estimated blood loss was 11.1±3.93 mL (range, 10 to 25 mL). The mean operative time was 102.3 minutes. There was minimal trauma to the bladder mucosa and no complications of fluid extravasation, hematuria, or urethral trauma were noted. All patients were discharged within 24 hours of the operation. Percutaneous cystolithotomy with the use of an entrapment bag is an efficient, safe technique for treating large volume bladder calculi. We recommend this technique as an alternative to open surgery for patients with too large a stone burden to remove transurethrally.

  20. Delta-sleep inducing peptide entrapment in the charged macroporous matrices

    Energy Technology Data Exchange (ETDEWEB)

    Sukhanova, Tatiana V., E-mail: sukhanovat@mail.ru [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Cell Interactions, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation); Artyukhov, Alexander A.; Gurevich, Yakov M.; Semenikhina, Marina A. [Mendeleyev University of Chemical Technology of Russia, Research and Teaching Center “Biomaterials”, Miusskaya sq., 9 Moscow (Russian Federation); Prudchenko, Igor A. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory of Peptide Chemistry, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation); Shtilman, Mikhail I. [Mendeleyev University of Chemical Technology of Russia, Research and Teaching Center “Biomaterials”, Miusskaya sq., 9 Moscow (Russian Federation); Markvicheva, Elena A. [Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Laboratory Polymers for Biology, Miklukho-Maklaya st., 16/10 Moscow (Russian Federation)

    2014-09-01

    Various biomolecules, for example proteins, peptides etc., entrapped in polymer matrices, impact interactions between matrix and cells, including stimulation of cell adhesion and proliferation. Delta-sleep inducing peptide (DSIP) possesses numerous beneficial properties, including its abilities in burn treatment and neuronal protection. DSIP entrapment in two macroporous polymer matrices based on copolymer of dimethylaminoethyl methacrylate and methylen-bis-acrylamide (Co-DMAEMA-MBAA) and copolymer of acrylic acid and methylen-bis-acrylamide (Co-AA-MBAA) has been studied. Quite 100% of DSIP has been entrapped into positively charged Co-DMAEMA-MBAA matrix, while the quantity of DSIP adsorbed on negatively charged Co-AA-MBAA was only 2–6%. DSIP release from Co-DMAEMA-MBAA was observed in saline solutions (0.9% NaCl and PBS) while there was no DSIP release in water or 25% ethanol, thus ionic strength was a reason of this process. - Graphical abstract: Delta-sleep inducing peptide possessing neuroprotective and wound healing properties was adsorbed on positively charged polymer matrix Co-DMAEMA-MBAA for tissue engineering. The peptide released from Co-DMAEMA-MBAA matrix in function of ionic strength of solution, pH decreasing stimulated peptide release from Co-DMAEMA-MBAA matrix for 3 h. This construction could be a base of new bioactive implants. - Highlights: • Macroporous positively charged Co-DMAEMA-MBAA matrix pore size was 20–35 μm. • DSIP was adsorbed on Co-DMAEMA-MBAA totally in 16 h. • Its release depends on ionic strength of solution (no release in 25% ethanol or water). • Co-DMAEMA-MBAA matrix swelling depends on pH and ionic strength of solution. • DSIP is destroyed in PBS and 0.9% NaCl in 5 days, but in water it was more stable.

  1. Can hydrocarbons entrapped in seep carbonates serve as gas geochemistry recorder?

    Science.gov (United States)

    Blumenberg, Martin; Pape, Thomas; Seifert, Richard; Bohrmann, Gerhard; Schlömer, Stefan

    2018-04-01

    The geochemistry of seep gases is useful for an understanding of the local petroleum system. Here it was tested whether individual light hydrocarbons in seep gases are representatively entrapped in authigenic carbonates that formed near active seep sites. If applicable, it would be possible to extract geochemical information not only on the origin but also on the thermal maturity of the hydrocarbon source rocks from the gases entrapped in carbonates in the past. Respective data could be used for a better understanding of paleoenvironments and might directly serve as calibration point for, amongst others, petroleum system modeling. For this approach, (sub)-recent seep carbonates from the Black Sea (Paleodnjepr region and Batumi seep area), two sites of the Campeche Knoll region in the Gulf of Mexico, and the Venere mud volcano (Mediterranean Sea) were selected. These seep carbonates derive from sites for which geochemical data on the currently seeping gases exist. During treatment with phosphoric acid, methane and higher hydrocarbons were released from all carbonates, but in low concentrations. Compositional studies demonstrate that the ratio of methane to the sum of higher hydrocarbons (C1/(C2+C3)) is (partly strongly) positively biased in the entrapped gas fraction. δ13C values of C1 were determined for all samples and, for the samples from the Gulf of Mexico and the Mediterranean Sea, also of C2 and C3. The present dataset from six seep sites indicates that information on the seeped methane can be—although with a scatter of several permil—recorded in seep carbonate matrices, but other valuable information like the composition and δ13C of ethane and propane appears to be modified or lost during, for example, enclosure or at an early stage of diagenesis.

  2. Entrapment of subtilisin in ceramic sol-gel coating for antifouling applications.

    Science.gov (United States)

    Regina, Viduthalai Rasheedkhan; Søhoel, Helmer; Lokanathan, Arcot Raghupathi; Bischoff, Claus; Kingshott, Peter; Revsbech, Niels Peter; Meyer, Rikke Louise

    2012-11-01

    Enzymes with antifouling properties are of great interest in developing nontoxic antifouling coatings. A bottleneck in developing enzyme-based antifouling coatings is to immobilize the enzyme in a suitable coating matrix without compromising its activity and stability. Entrapment of enzymes in ceramics using the sol-gel method is known to have several advantages over other immobilization methods. The sol-gel method can be used to make robust coatings, and the aim of this study was to explore if sol-gel technology can be used to develop robust coatings harboring active enzymes for antifouling applications. We successfully entrapped a protease, subtilisin (Savinase, Novozymes), in a ceramic coating using a sol-gel method. The sol-gel formulation, when coated on a stainless steel surface, adhered strongly and cured at room temperature in less than 8 h. The resultant coating was smoother and less hydrophobic than stainless steel. Changes in the coating's surface structure, thickness and chemistry indicate that the coating undergoes gradual erosion in aqueous medium, which results in release of subtilisin. Subtilisin activity in the coating increased initially, and then gradually decreased. After 9 months, 13% of the initial enzyme activity remained. Compared to stainless steel, the sol-gel-coated surfaces with active subtilisin were able to reduce bacterial attachment of both Gram positive and Gram negative bacteria by 2 orders of magnitude. Together, our results demonstrate that the sol-gel method is a promising coating technology for entrapping active enzymes, presenting an interesting avenue for enzyme-based antifouling solutions.

  3. Experimental chronic entrapment of the sciatic nerve in adult hamsters: an ultrastructural and morphometric study

    Directory of Open Access Journals (Sweden)

    Prinz R.A.D.

    2003-01-01

    Full Text Available Entrapment neuropathy is a group of clinical disorders involving compression of a peripheral nerve and interference with nerve function mostly through traction injury. We have investigated the chronic compression of peripheral nerves as an experimental procedure for detecting changes in ultrastructural nerve morphology. Adult hamsters (Mesocricetus auratus, N = 30 were anesthetized with a 25% pentobarbital solution and received a cuff around the right sciatic nerve. Left sciatic nerves were not operated (control group. Animals survived for varying times (up to 15 weeks, after which they were sacrificed and both sciatic nerves were immediately fixed with a paraformaldehyde solution. Experimental nerves were divided into segments based upon their distance from the site of compression (proximal, entrapment and distal. Semithin and ultrathin sections were obtained and examined by light and electron microscopy. Ultrastructural changes were qualitatively described and data from semithin sections were morphometrically analyzed both in control and in compressed nerves. We observed endoneurial edema along with both perineurial and endoneurial thickening and also the existence of whorled cell-sparse structures (Renaut bodies in the subperineurial space of compressed sciatic nerves. Morphometric analyses of myelinated axons at the compression sites displayed a remarkable increase in the number of small axons (up to 60% in comparison with the control axonal number. The distal segment of compressed nerves presented a distinct decrease in axon number (up to 40% comparatively to the control group. The present experimental model of nerve entrapment in adult hamsters was shown to promote consistent histopathologic alterations analogous to those found in chronic compressive neuropathies.

  4. An Endovascular Approach to the Entrapped Central Venous Catheter After Cardiac Surgery

    Energy Technology Data Exchange (ETDEWEB)

    Desai, Shamit S., E-mail: shamit.desai@northwestern.edu [Northwestern Memorial Hospital, Department of Radiology (United States); Konanur, Meghana [Northwestern University Feinberg School of Medicine (United States); Foltz, Gretchen [Mallinckrodt Institute of Radiology at Washington University, Interventional Radiology (United States); Malaisrie, S. Chris [Northwestern Memorial Hospital, Department of Cardiothoracic Surgery (United States); Resnick, Scott, E-mail: sresnick@northwestern.edu [Northwestern University Feinberg School of Medicine, Department of Radiology, Interventional Radiology, Northwestern Memorial Hospital (United States)

    2016-03-15

    PurposeEntrapment of central venous catheters (CVC) at the superior vena cava (SVC) cardiopulmonary bypass cannulation site by closing purse-string sutures is a rare complication of cardiac surgery. Historically, resternotomy has been required for suture release. An endovascular catheter release approach was developed.Materials and MethodsFour cases of CVC tethering against the SVC wall and associated resistance to removal, suggestive of entrapment, were encountered. In each case, catheter removal was achieved using a reverse catheter fluoroscopically guided over the suture fixation point between catheter and SVC wall, followed by the placement of a guidewire through the catheter. The guidewire was snared and externalized to create a through-and-through access with the apex of the loop around the suture. A snare placed from the femoral venous access provided concurrent downward traction on the distal CVC during suture release maneuvers.ResultsIn the initial attempt, gentle traction freed the CVC, which fractured and was removed in two sections. In the subsequent three cases, traction alone did not release the CVC. Therefore, a cutting balloon was introduced over the guidewire and inflated. Gentle back-and-forth motion of the cutting balloon atherotomes successfully incised the suture in all three attempts. No significant postprocedural complications were encountered. During all cases, a cardiovascular surgeon was present in the interventional suite and prepared for emergent resternotomy, if necessary.ConclusionAn endovascular algorithm to the “entrapped CVC” is proposed, which likely reduces risks posed by resternotomy to cardiac surgery patients in the post-operative period.

  5. An Endovascular Approach to the Entrapped Central Venous Catheter After Cardiac Surgery

    International Nuclear Information System (INIS)

    Desai, Shamit S.; Konanur, Meghana; Foltz, Gretchen; Malaisrie, S. Chris; Resnick, Scott

    2016-01-01

    PurposeEntrapment of central venous catheters (CVC) at the superior vena cava (SVC) cardiopulmonary bypass cannulation site by closing purse-string sutures is a rare complication of cardiac surgery. Historically, resternotomy has been required for suture release. An endovascular catheter release approach was developed.Materials and MethodsFour cases of CVC tethering against the SVC wall and associated resistance to removal, suggestive of entrapment, were encountered. In each case, catheter removal was achieved using a reverse catheter fluoroscopically guided over the suture fixation point between catheter and SVC wall, followed by the placement of a guidewire through the catheter. The guidewire was snared and externalized to create a through-and-through access with the apex of the loop around the suture. A snare placed from the femoral venous access provided concurrent downward traction on the distal CVC during suture release maneuvers.ResultsIn the initial attempt, gentle traction freed the CVC, which fractured and was removed in two sections. In the subsequent three cases, traction alone did not release the CVC. Therefore, a cutting balloon was introduced over the guidewire and inflated. Gentle back-and-forth motion of the cutting balloon atherotomes successfully incised the suture in all three attempts. No significant postprocedural complications were encountered. During all cases, a cardiovascular surgeon was present in the interventional suite and prepared for emergent resternotomy, if necessary.ConclusionAn endovascular algorithm to the “entrapped CVC” is proposed, which likely reduces risks posed by resternotomy to cardiac surgery patients in the post-operative period

  6. Vascular Entrapment of Both the Sciatic and Pudendal Nerves Causing Persistent Sciatica and Pudendal Neuralgia.

    Science.gov (United States)

    Kale, Ahmet; Basol, Gulfem; Usta, Taner; Cam, Isa

    2018-04-24

    To demonstrate the laparoscopic approach to malformed branches of the vessels entrapping the nerves of the sacral plexus. A step-by-step explanation of the surgery using video (educative video) (Canadian Task force classification II). The university's Ethics Committee ruled that approval was not required for this video. Kocaeli Derince Education and Research Hospital, Kocaeli, Turkey. A 26-year-old patient who had failed medical therapy and presented with complaints of numbness and burning pain on the right side of her vagina and pain radiating to her lower limbs for a period of approximately 36 months. The peritoneum was incised along the external iliac vessels, and these vessels were separated from the iliopsoas muscle on the right side of the pelvis. The laparoscopic decompression of intrapelvic vascular entrapment was performed at 3 sites: the lumbosacral trunk, sciatic nerve, and pudendal nerve. The aberrant dilated veins were gently dissected from nerves, and then coagulated and cut with the LigaSure sealing device (Medtronic, Minneapolis, Minn). The operation was completed successfully with no complications, and the patient was discharged from the hospital 24 hours after the operation. At a 6-month follow-up, she reported complete resolution of dyspareunia and sciatica (visual analog scale score 1 of 10). A less well-known cause of chronic pelvic pain is compression of the sacral plexus by dilated or malformed branches of the internal iliac vessels. Laparoscopic management of vascular entrapment of the sacral plexus has been described by Possover et al [1,2] and Lemos et al [3]. This procedure appears to be feasible and effective, but requires significant experience and familiarity with laparoscopy techniques and pelvic nerve anatomy. Copyright © 2018 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.

  7. New High: A Future-Oriented Study of American Drug Policy

    Science.gov (United States)

    2017-12-01

    physical health , leading to a decrease in morbidity and mortality from obesity. Nootropics on pharmacy shelves combat hunger, low energy, and...office of the future. 14. SUBJECT TERMS futures, megatrends, emerging technologies, drug policy, public health , war on drugs, forecasting, behavioral... health , scenarios, trends, innovation, regulation, policy, artificial intelligence, brain-computer interface, neural stimulation, nootropics

  8. Novel High-Throughput Drug Screening Platform for Chemotherapy-Induced Axonal Neuropathy

    Science.gov (United States)

    2014-05-01

    from anti-cancer drug therapy [1,2]. Platinum drugs, taxanes, proteasome inhibitors, vinca alkaloids, epothilones, and immunomodulators are the...and immunomodulators are the standard of anti-cancer therapies for the six most cancers. An estimated 2010 incidence of 994, 680 cases for these

  9. HIV prevention through drugs and sex education in junior high schools in Bandung West Java: the teachers' perspective.

    Science.gov (United States)

    Hinduan, Zahrotur R; Riyanti, Eka; Tasya, Irma A; Pohan, Mawar N; Sumintardja, Elmira N; Astuti, Sri R; Jabar, Bambang A; Pinxten, Lucas Wj; Hospers, Harm J

    2009-07-01

    to explore the teacher perspective on needs (in terms of knowledge, skills and curriculum content), attitudes, beliefs and self-efficacy related to teaching and implementation of a reproductive health (RH)/drug education (DE) program at their own junior high school. one hundred and thirty-three teachers participated in a survey, from February to April 2009, measuring: socio demographic, behavioral intention, perceived behavior control, content knowledge, school climate, reproductive health knowledge and school drug education. all teachers had a high intention to teach RH and DE, especially the younger RH teachers had a high intention to teach about teenage pregnancy and sexually transmitted infections. DE teachers had a high intention facts/effects of drugs, first-time drug use dealing with peer pressure. Perceived beliefs of teachers, parents, school management and perceived self-efficacy were strong predictors for the intention of RH teaching and DE. the high intention of the RH and DE teacher offers a great opportunity to build and implement a DE and RH curriculum in junior high school. Before a curriculum is developed and implemented there is a need to assess and strengthen the teacher's skills and effectiveness in teaching RH and DE.

  10. Trojan Microparticles for Drug Delivery

    Directory of Open Access Journals (Sweden)

    Thierry F. Vandamme

    2012-01-01

    Full Text Available During the last decade, the US Food and Drug Administration (FDA have regulated a wide range of products, (foods, cosmetics, drugs, devices, veterinary, and tobacco which may utilize micro and nanotechnology or contain nanomaterials. Nanotechnology allows scientists to create, explore, and manipulate materials in nano-regime. Such materials have chemical, physical, and biological properties that are quite different from their bulk counterparts. For pharmaceutical applications and in order to improve their administration (oral, pulmonary and dermal, the nanocarriers can be spread into microparticles. These supramolecular associations can also modulate the kinetic releases of drugs entrapped in the nanoparticles. Different strategies to produce these hybrid particles and to optimize the release kinetics of encapsulated drugs are discussed in this review.

  11. Endovascular Retrieval of Entrapped Elephant Trunk Graft During Complex Hybrid Aortic Arch Repair

    Energy Technology Data Exchange (ETDEWEB)

    Damodharan, Karthikeyan, E-mail: drdkarthik@hotmail.com [Singapore General Hospital, Department of Diagnostic Radiology (Singapore); Chao, Victor T. T., E-mail: victor.chao.t.t@singhealth.com.sg [National Heart Centre, Department of Cardiothoracic Surgery (Singapore); Tay, Kiang Hiong, E-mail: tay.kiang.hiong@singhealth.com.sg [Singapore General Hospital, Department of Diagnostic Radiology (Singapore)

    2016-12-15

    Entrapment of the elephant trunk graft within the false lumen is a rare complication of surgical repair of an aortic dissection. This is normally retrieved by emergent open surgery. We describe a technique of endovascular retrieval of the dislodged graft, during hybrid aortic arch repair. The elephant trunk was cannulated through and through from a femoral access and the free end of the wire was snared and retrieved from a brachial access. The wire was externalised from both accesses and was used to reposition the graft into the true lumen using a body flossing technique.

  12. A study on entrapment: splashing of liquid UO2 over small sodium volumes

    International Nuclear Information System (INIS)

    Schins, H.; Klein, K.; Jorzik, E.

    1978-01-01

    Three experiments were done in which each time more than 1 kg of liqid UO 2 was splashed over a plate in which different stainless steel cups full of sodium were contained. No whatsoever indication of entrapment of sodium could be found. The pressure tests indicate up to 1,8 atm and they relax in some second time. These pressure diagrams have been satisfactorily analysed as indicating a sodium vapor formation. In the third experiment e.g. the quenching of 800 g UO 2 in 720 g of sodium in a closed volume of argon of 225 l will provide the requested maximum pressure

  13. Entrapment of the Martin-Gruber branch of median nerve in the forearm

    Directory of Open Access Journals (Sweden)

    Anu Vinod Ranade

    2016-07-01

    Full Text Available We report a rare case of a dual neuro-vascular variation, which was observed in the right extremity of male cadaver. About an inch inferior to the elbow joint, three branches arose from the median nerve. These were the anterior interosseous branch, a Martin-Gruber branch (MGB and a muscular branch. The MGB coursed infero-medially to join with the ulnar nerve by running posterior to the ulnar artery. It was surprising to observe that the MGB passed between the ulnar artery and its venae comitantes. There was an acute angulation of the MGB here, suggesting entrapment at this site.

  14. Neuropatia Periférica Familiar por Susceptibilidade ao Entrapment (Neuropatia Tomaculosa)

    OpenAIRE

    Pinto Viana, J; Coimbra, J; Goulart, Z; Bigotte de Almeida, L; Cabral Beirão, J

    1991-01-01

    Os autores apresentam um caso de neuropatia periférica familiar por susceptibilidade ao entrapment e comparam-no com os descritos na literatura. As principais características desta neuropatia são: hereditariedade autossómica dominante, mononeuropatias recorrentes de localização variável (cubital, mediano, ciático poplíteo, externo, plexo braquial) e aspectos morfológicos característicos na biópsia do nervo. O nervo sensitivo revela alterações predominantes desmielinizantes, com espessamentos ...

  15. Segmental jejunal entrapment, volvulus, and strangulation secondary to intra-abdominal adhesions in a dog.

    Science.gov (United States)

    Di Cicco, Michael F; Bennett, R Avery; Ragetly, Chantal; Sippel, Kate M

    2011-01-01

    A 4 yr old, castrated male dachshund was presented for lethargy, restlessness, a "hunched" posture, and a painful abdomen. A gastric foreign body had been surgically removed 24 mo previously. Exploratory celiotomy revealed a devitalized segment of jejunum with twisted mesentery. Several adhesions and fibrous bands were present within the abdomen, presumptively from the previous gastric foreign body surgery. Histopathology determined that a fibrous tissue band caused entrapment of the segment of intestine and its mesentery resulting in volvulus and ischemic necrosis of the intestine. This case is unique because it involved a focal area of the jejunum that was incarcerated in fibrous adhesions.

  16. Post coital penile ring entrapment: A report of a non-surgical extrication method

    Directory of Open Access Journals (Sweden)

    Agu Thaddeus Chika

    2016-01-01

    Full Text Available This case report shows how a simple but painstaking method of milking and levering in a slippery field was used to remove a thick metallic ring entrapped at the root of the penis after sexual intercourse. A ring can be removed easily from an organ if the inter-phase is made slippery. However this must be weighed against the handling difficulties posed by a wet slippery surface. With perseverance and the use of unconventional instrument, the ring was successfully extricated as a day case and without a surgical incision.

  17. Dry coating of micronized API powders for improved dissolution of directly compacted tablets with high drug loading.

    Science.gov (United States)

    Han, Xi; Ghoroi, Chinmay; Davé, Rajesh

    2013-02-14

    Motivated by our recent study showing improved flow and dissolution rate of the active pharmaceutical ingredient (API) powders (20 μm) produced via simultaneous micronization and surface modification through continuous fluid energy milling (FEM) process, the performance of blends and direct compacted tablets with high drug loading is examined. Performance of 50 μm API powders dry coated without micronization is also considered for comparison. Blends of micronized, non-micronized, dry coated or uncoated API powders at 30, 60 and 70% drug loading, are examined. The results show that the blends containing dry coated API powders, even micronized ones, have excellent flowability and high bulk density compared to the blends containing uncoated API, which are required for direct compaction. As the drug loading increases, the difference between dry coated and uncoated blends is more pronounced, as seen in the proposed bulk density-FFC phase map. Dry coating led to improved tablet compactibility profiles, corresponding with the improvements in blend compressibility. The most significant advantage is in tablet dissolution where for all drug loadings, the t(80) for the tablets with dry coated APIs was well under 5 min, indicating that this approach can produce nearly instant release direct compacted tablets at high drug loadings. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. How to calculate clearance of highly protein-bound drugs during continuous venovenous hemofiltration demonstrated with flucloxacillin.

    Science.gov (United States)

    Meyer, Brigitte; Ahmed el Gendy, Salwa; Delle Karth, Georg; Locker, Gottfried J; Heinz, Gottfried; Jaeger, Walter; Thalhammer, Florian

    2003-01-01

    Flucloxacillin is an important antimicrobial drug in the treatment of infections with Staphylococcus aureus and therefore is often used in staphylococcal infections. Furthermore, flucloxacillin has a high protein binding rate as for example ceftriaxone or teicoplanin--drugs which have formerly been characterized as not being dialyzable. The pharmacokinetic parameters of 4.0 g flucloxacillin every 8 h were examined in 10 intensive care patients during continuous venovenous hemofiltration (CVVH) using a polyamide capillary hemofilter. In addition, the difficulty of calculating the hemofiltration clearance of a highly protein-bound drug is described. Flucloxacillin serum levels were significantly lowered (56.9 +/- 24.0%) even though only 15% of the drug was detected in the ultrafiltrate. Elimination half-life, total body clearance and sieving coefficient were 4.9 +/- 0.7 h, 117.2 +/- 79.1 ml/min and 0.21 +/- 0.09, respectively. These discrepancies can be explained by the high protein binding of flucloxacillin, the adsorbing property of polyamide and the equation in order to calculate hemofiltration clearance. The unbound fraction of a 4.0 g flucloxacillin dosage facilitates time above the minimum inhibitory concentration (T > MIC) of 60% only for strains up to a minimum inhibitory concentration (MIC) of 0.5 mg/l. Based on the data of this study, we conclude that intensive care patients with staphylococcal infections on CVVH should be treated with 4.0 g flucloxacillin every 8 h which was safe and well tolerated. Moreover, further studies with highly protein-bound drugs are recommended to check the classical 'hemodialysis' equation as the standard equation in calculating the CVVH clearance of highly protein-bound drugs. Copyright 2003 S. Karger AG, Basel

  19. Exploration of genetically determined resistance against hepatitis C infection in high-risk injecting drug users.

    Science.gov (United States)

    Sugden, P B; Cameron, B; Luciani, F; Lloyd, A R

    2014-08-01

    Genetic resistance to specific infections is well recognized. In hepatitis C virus (HCV) infection, genetic polymorphisms in IL-28B and the killer cell immunoglobulin-like receptors (KIR) and their HLA class I ligands have been shown to affect clearance of the virus following infection. There are limited data regarding resistance to established HCV infection. Reliable quantification of repeated exposure in high-risk populations, such as injecting drug users (IDU), is a key limitation of previous studies of resistance. Behavioural data and DNA from IDU (n = 210) in the Hepatitis C Incidence and Transmission Study in prisons (HITS-p) cohort were genotyped for polymorphisms in: IL-28B, peptidyl-prolyl isomerase A (PPIA), HLA-C and KIR2. To quantify risk, a composite risk index based on factors predictive of incident HCV infection was derived. Logistic regression analysis revealed the risk index was strongly associated with incident HCV infection (P C1, or their combination. A framework for the investigation of genetic determinants of resistance to HCV infection has been developed. Several candidate gene associations were investigated and excluded. Further investigation of genetic determinants of resistance to HCV infection is warranted. © 2014 John Wiley & Sons Ltd.

  20. Mini-tablets versus pellets as promising multiparticulate modified release delivery systems for highly soluble drugs.

    Science.gov (United States)

    Gaber, Dina M; Nafee, Noha; Abdallah, Osama Y

    2015-07-05

    Whether mini-tablets (tablets, diameters ≤6mm) belong to single- or multiple-unit dosage forms is still questionable. Accordingly, Pharmacopoeial evaluation procedures for mini-tablets are lacking. In this study, the aforementioned points were discussed. Moreover, their potential for oral controlled delivery was assessed. The antidepressant venlafaxine hydrochloride (Vx), a highly soluble drug undergoing first pass effect, low bioavailability and short half-life was selected as a challenging payload. In an attempt to weigh up mini-tablets versus pellets as multiparticulate carriers, Vx-loaded mini-tablets were compared to formulated pellets of the same composition and the innovator Effexor(®)XR pellets. Formulations were prepared using various polymer hydrogels in the core and ethyl cellulose film coating with increasing thickness. Mini-tablets (diameter 2mm) showed extended Vx release (<60%, 8h). Indeed, release profiles comparable to Effexor(®)XR pellets were obtained. Remarkably higher coating thickness was required for pellets to provide equivalent retardation. Ethyl cellulose in the core ensured faster release due to polymer migration to the surface and pore formation in the coat. mini-tablets showed higher stability to pellets upon storage. Industrially speaking, mini-tablets proved to be superior to pellets in terms of manufacturing, product quality and economical aspects. Results point out the urgent need for standardized evaluation procedures for mini-tablets. Copyright © 2015. Published by Elsevier B.V.

  1. [Access to high-cost drugs in Brazil from the perspective of physicians, pharmacists and patients].

    Science.gov (United States)

    Rover, Marina Raijche Mattozo; Vargas-Pelaez, Claudia Marcela; Rocha Farias, Mareni; Nair Leite, Silvana

    2016-01-01

    To explore perceptions on access to medication supplied by the Specialized Component of Pharmaceutical Assistance (CEAF) within the Brazilian Unified Health System (which includes high-cost drugs) by the actors involved in the healthcare services of this component. A descriptive, qualitative study was carried out by using a focal group with 7 users and 11 semi-structured interviews with health professionals (physicians and pharmacist) in the state of Santa Catarina. According to the participants, access to medicines had improved. Two main perceptions of the CEAF Clinical Guidelines were identified: the requirements constitute a bureaucracy that limits access, and the requisites increase the demand for tests and specialized healthcare services, exceeding the capacity of the healthcare services network. These assumptions generated the search for other means of access that revealed a lack of information and understanding of the right to health among the users. In addition, according to the participants, because of the difficulties of accessing services as a whole, full access to CEAF medicines is a goal that remains to be achieved. Although access to CEAF medicines has improved, there are still some difficulties in guaranteeing treatment access and comprehensiveness. Copyright © 2016 SESPAS. Published by Elsevier Espana. All rights reserved.

  2. Multi-residue determination of 210 drugs in pork by ultra-high-performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Yin, Zhiqiang; Chai, Tingting; Mu, Pengqian; Xu, Nana; Song, Yue; Wang, Xinlu; Jia, Qi; Qiu, Jing

    2016-09-09

    This paper presents a multi-residue analytical method for 210 drugs in pork using ultra-high-performance liquid chromatography-Q-Trap tandem mass spectrometry (UPLC-MS/MS) within 20min via positive ESI in scheduled multi-reaction monitoring (MRM) mode. The 210 drugs, belonging to 21 different chemical classes, included macrolides, sulfonamides, tetracyclines, β-lactams, β-agonists, aminoglycosides, antiviral drugs, glycosides, phenothiazine, protein anabolic hormones, non-steroidal anti-inflammatory drugs (NSAIDs), quinolones, antifungal drugs, corticosteroids, imidazoles, piperidines, piperazidines, insecticides, amides, alkaloids and others. A rapid and simple preparation method was applied to process the animal tissues, including solvent extraction with an acetonitrile/water mixture (80/20, v/v), defatting and clean-up processes. The recoveries ranged from 52% to 130% with relative standard deviations (RSDs)<20% for spiked concentrations of 10, 50 and 250μg/kg. More than 90% of the analytes achieved low limits of quantification (LOQs)<10μg/kg. The decision limit (CCα), detection capability (CCβ) values were in the range of 2-502μg/kg and 4-505μg/kg, respectively. This method is significant for food safety monitoring and controlling veterinary drug use. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. A novel hanging spherical drop system for the generation of cellular spheroids and high throughput combinatorial drug screening.

    Science.gov (United States)

    Neto, A I; Correia, C R; Oliveira, M B; Rial-Hermida, M I; Alvarez-Lorenzo, C; Reis, R L; Mano, J F

    2015-04-01

    We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.

  4. Effects of inoculum type and bulk dissolved oxygen concentration on achieving partial nitrification by entrapped-cell-based reactors.

    Science.gov (United States)

    Rongsayamanont, Chaiwat; Limpiyakorn, Tawan; Khan, Eakalak

    2014-07-01

    An entrapment of nitrifiers into gel matrix is employed as a tool to fulfill partial nitrification under non-limiting dissolved oxygen (DO) concentrations in bulk solutions. This study aims to clarify which of these two attributes, inoculum type and DO concentration in bulk solutions, is the decisive factor for partial nitrification in an entrapped-cell based system. Four polyvinyl alcohol entrapped inocula were prepared to have different proportions of nitrite-oxidizing bacteria (NOB) and nitrite-oxidizing activity. At a DO concentration of 3 mg l(-1), the number of active NOB cells in an inoculum was the decisive factor for partial nitrification enhancement. However, when the DO concentration was reduced to 2 mg l(-1), all entrapped cell inocula showed similar degrees of partial nitrification. The results suggested that with the lower bulk DO concentration, the preparation of entrapped cell inocula is not useful as the DO level becomes the decisive factor for achieving partial nitrification. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. A meta-analysis of perceptions of defeat and entrapment in depression, anxiety problems, posttraumatic stress disorder, and suicidality.

    Science.gov (United States)

    Siddaway, Andy P; Taylor, Peter J; Wood, Alex M; Schulz, Joerg

    2015-09-15

    There is a burgeoning literature examining perceptions of being defeated or trapped in different psychiatric disorders. The disorders most frequently examined to date are depression, anxiety problems, posttraumatic stress disorder (PTSD), and suicidality. To quantify the size and consistency of perceptions of defeat and entrapment in depression, anxiety problems, PTSD and suicidality, test for differences across psychiatric disorders, and examine potential moderators and publication bias. Random-effects meta-analyses based on Pearson's correlation coefficient r. Forty studies were included in the meta-analysis (n = 10,072). Perceptions of defeat and entrapment were strong (around r = 0.60) and similar in size across all four psychiatric disorders. Perceptions of defeat were particularly strong in depression (r = 0.73). There was no between-study heterogeneity; therefore moderator analyses were conducted in an exploratory fashion. There was no evidence of publication bias. Analyses were cross-sectional, which precludes establishing temporal precedence or causality. Some of the meta-analyses were based on relatively small numbers of effect sizes, which may limit their generalisability. Perceptions of defeat and entrapment are clinically important in depression, anxiety problems, PTSD, and suicidality. Similar-sized, strong relationships across four different psychiatric disorders could suggest that perceptions of defeat and entrapment are transdiagnostic constructs. The results suggest that clinicians and researchers need to become more aware of perceptions of defeat and entrapment. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Rapid screening for drugs of abuse in biological fluids by ultra high performance liquid chromatography/Orbitrap mass spectrometry.

    Science.gov (United States)

    Jagerdeo, Eshwar; Schaff, Jason E

    2016-08-01

    We present a UPLC(®)-High Resolution Mass Spectrometric method to simultaneously screen for nineteen benzodiazepines, twelve opiates, cocaine and three metabolites, and three "Z-drug" hypnotic sedatives in both blood and urine specimens. Sample processing consists of a high-speed, high-temperature enzymatic hydrolysis for urine samples followed by a rapid supported liquid extraction (SLE). The combination of ultra-high resolution chromatography with high resolution mass spectrometry allows all 38 analytes to be uniquely detected with a ten minute analytical run. Limits of detection for all target analytes are 3ng/mL or better, with only 0.3mL of specimen used for analysis. The combination of low sample volume with fast processing and analysis makes this method a suitable replacement for immunoassay screening of the targeted drug classes, while providing far superior specificity and better limits of detection than can routinely be obtained by immunoassay. Published by Elsevier B.V.

  7. High prevalence of drug-resistant tuberculosis, Republic of Lithuania, 2002

    DEFF Research Database (Denmark)

    Dewan, P; Sosnovskaja, A; Thomsen, V

    2005-01-01

    BACKGROUND: Nations of the former Soviet Union have the world's highest reported levels of resistance to anti-tuberculosis drugs. We conducted the first national survey of anti-tuberculosis drug resistance in the Republic of Lithuania. METHODS: We tested Mycobacterium tuberculosis isolates from all...... isolates, 475 (41%) were resistant to at least one first-line drug, and 263 (23%) were resistant to at least INH and RMP (MDR); this included 76/818 (9.3%) from new patients and 187/345 (54%) from previously treated patients. Of 52 MDR isolates randomly selected for extended testing at an international...

  8. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Jian-Bo [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Nan; Pan, Wen; Hong, Ru [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Wang, Hao [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Zhi-Liang, E-mail: appo@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China)

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.

  9. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    International Nuclear Information System (INIS)

    Pan, Jian-Bo; Ji, Nan; Pan, Wen; Hong, Ru; Wang, Hao; Ji, Zhi-Liang

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified

  10. [Comparison of family functioning profile in adolescents with and without drug-dependency in a high school].

    Science.gov (United States)

    Cruz-Salmerón, Víctor Hugo; Martínez-Martínez, Martha Leticia; Garibay-López, Leticia; Camacho-Calderón, Nicolás

    2011-02-01

    To compare the family functioning profile (FFP) in adolescents addicted to drugs and those not addicted to drugs. Cross-sectional study comparative. A high school in Querétaro State, Mexico. Study of 63 adolescents with and without addiction, of both sexes between the ages of 13 and 19, enrolled in high school; two groups formed, one not addicted to drugs (systematic probabilistic sampling was carried out); and compared with drug addicts (database). FFP(Alpha Cronbach 91). Descriptive and inferential statistical analysis. Adolescents with drug addiction (n=20), average age 17.5±0.4 (range 16-19), and group of non-addicts (n=43), average age 16.9±0.1 (range 15-18) and P=0.000. All the adolescents lived in an urban area with a predominantly simple nuclear modern, working family type. Half (50%) of addicted adolescents came from broken families P=0.002. The dispersion phase was a protective factor in preventing drug addiction in adolescents (P=0.003 OR 0.6 95% Cl;1.8-21.0). Significant statistical differences were observed in authority (OR=29.7, 95% Cl; 5.8-150.5), supervision (OR 10.3, 95% Cl; 2.8-37.2) and support (OR 0.04, 95% Cl; 5.5-109.8). The overall family dysfunctionality, (P=0.000, OR 1.8, 95% Cl; 1.3-2.3). Dysfunctional families are a risk factor for drug addiction in adolescents, when there is insufficient authority and supervision within the family. On the other hand, family support, as well as the dispersion phase, are protective factors. Copyright © 2010 Elsevier España, S.L. All rights reserved.

  11. Ionic effect investigation of a potentiometric sensor for urea and surface morphology observation of entrapped urease/polypyrrole matrix.

    Science.gov (United States)

    Syu, Mei-Jywan; Chang, Yu-Sung

    2009-04-15

    Potentio-dynamic polymerization of buffered urease and pyrrole monomer onto carbon papers was conducted to fabricate an immobilized urease electrode for measuring the urea concentration. To use carbon paper as the substrate for the electro-growth of polypyrrole matrix not only created sufficient adhesion of the conducting polymer layer but also provided superior entrapment of urease enzymes. The potentiometric response corresponding to ammonia, the product formed from the urease catalyzed urea reaction, was employed for the urea concentration measurement. Scanning electron microscopic photographs showed that the polypyrrole matrix deposited on the carbon papers appeared to be of a cylindrical nanotube shape. The charge density applied in the polymerization was found to affect the potentiometric response while the potential-scanning rate showed minor influence. The composite electrodes had high sensitivity in urea detection, showing a response linear to the logarithm of the urea concentration in the range of 10(-3) to 10 mM. The detection of urea solution prepared in water and buffer was also compared. Ionic effect on the sensing of urea solution was investigated. By comparing the data reported in literature, the urease/polypyrrole/carbon paper electrode developed in this work showed superior long-term stability and reusability. The detection of urea in serum was also well performed.

  12. Development and validation of a fast RP-HPLC method for determination of methotrexate entrapment efficiency in polymeric nanocapsules.

    Science.gov (United States)

    Sartori, Tatiane; Seigi Murakami, Fabio; Pinheiro Cruz, Ariane; Machado de Campos, Angela

    2008-07-01

    A rapid and effective isocratic chromatographic procedure is successfully developed to determinate methotrexate (MTX) entrapment efficiency (EE) in polymeric nanocapsules using reversed-phase high-performance liquid chromatography. The method employed a RP-C(18) Shimadzu Shim-pack CLC-ODS (150 mm x 4.6 mm, 5 microm) column with mobile phase constituted by a mixture of water-acetonitrile-tetrahydrofuran (65:30:5 v/v/v; pH 3.0) at a flow rate of 0.8 mL/min. The eluate is monitored with a UV detector set at 313 nm. The parameters used in the validation process are: linearity, specificity, precision, accuracy, and limit of quantitation (LOQ). The linearity is evaluated by a calibration curve in the concentration range of 10-50 microg/mL and presented a correlation coefficient of 0.9998. The polymers (PLA or PLA-PEG), oil, and surfactants used in the nanocapsule formulation did not interfere with analysis and the recovery was quantitative. The intra and inter-day assay relative standard deviation were less than 0.72%. Results are satisfactory, and the method proved to be adequate for the determination of methotrexate in nanocapsules formulations.

  13. Application of 10BSH entrapped transferrin-PEG-liposome to boron neutron-capture therapy (BNCT) for solid tumor

    International Nuclear Information System (INIS)

    Maruyama, K.; Ishida, O.; Iwatsuru, M.; Yanagie, H.; Eriguchi, M.; Kobayashi, H.

    2000-01-01

    The successful treatment of cancer by BNCT requires the selective concentration of 10 B within malignant tumor cells. Intracellular targeting ability and cytotoxic effects of 10 B entrapped TF-PEG-liposomes, in which TF is covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes, were examined in Colon 26 tumor-bearing mice. TF-PEG-liposomes readily bound to tumor cells in vivo, and were internalized by receptor-mediated endocytosis. 10 B-PEG-liposomes and 10 B-TF-PEG-liposomes showed prolonged residence time in the circulation and low RES uptake in tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue and reached high level of 10 B content in tumor. After thermal neutron irradiation of mice injected with 10 B-PEG-liposomes or 10 B-TF-PEG-liposome, tumor growth was suppressed relative to controls. These results suggest that intravenous injection of 10 B TF-PEG-liposome can increase the intracellular retention of 10 B atoms, which were introduced by receptor mediated endocytosis after binding, causing tumor growth suppression in vivo upon thermal neutron irradiation. (author)

  14. Triggering and Energetics of a Single Drop Vapor Explosion: The Role of Entrapped Non-Condensable Gases

    Energy Technology Data Exchange (ETDEWEB)

    Hansson, Roberta Concilio [Royal Institute of Technology, Stockholm (Sweden)

    2009-11-15

    The present work pertains to a research program to study Molten Fuel-Coolant Interactions (MFCI), which may occur in a nuclear power plant during a hypothetical severe accident. Dynamics of the hot liquid (melt) droplet and the volatile liquid (coolant) were investigated in the MISTEE (Micro-Interactions in Steam Explosion Experiments) facility by performing well-controlled, externally triggered, single-droplet experiments, using a high-speed visualization system with synchronized digital cinematography and continuous X-ray radiography. The current study is concerned with the MISTEE-NCG test campaign, in which a considerable amount of non-condensable gases (NCG) are present in the film that enfolds the molten droplet. The SHARP images for the MISTEE-NCG tests were analyzed and special attention was given to the morphology (aspect ratio) and dynamics of the air/ vapor bubble, as well as the melt drop preconditioning. Energetics of the vapor explosion (conversion ratio) were also evaluated. The MISTEE.NCG tests showed two main aspects when compared to the MISTEE test series (without entrapped air). First, analysis showed that the melt preconditioning still strongly depends on the coolant subcooling. Second, in respect to the energetics, the tests consistently showed a reduced conversion ratio compared to that of the MISTEE test series

  15. Sexual behavior among high school students in Brazil: alcohol consumption and legal and illegal drug use associated with unprotected sex

    Directory of Open Access Journals (Sweden)

    Zila M. Sanchez

    2013-04-01

    Full Text Available OBJECTIVE: Alcohol and other drug use appears to reduce decision-making ability and increase the risk of unsafe sex, leading to possible unplanned pregnancies, sexually transmitted diseases/human immunodeficiency virus/HIV transmission, and multiple sexual partners. This study aimed to test the hypothesis that risky sexual behaviors among adolescents are associated with legal and illegal drug use. METHODS: A national cross-sectional survey of 17,371 high-school students was conducted in 2010. Students were selected from 789 public and private schools in each of the 27 Brazilian state capitals by a multistage probabilistic sampling method and answered a self-report questionnaire. Weighted data were analyzed through basic contingency tables and logistic regressions testing for differences in condom use among adolescents who were sexually active during the past month. RESULTS: Approximately one third of the high school students had engaged in sexual intercourse in the month prior to the survey, and nearly half of these respondents had not used a condom. While overall sexual intercourse was more prevalent among boys, unsafe sexual intercourse was more prevalent among girls. Furthermore, a lower socioeconomic status was directly associated with non-condom use, while binge drinking and illegal drug use were independently associated with unsafe sexual intercourse. CONCLUSION: Adolescent alcohol and drug use were associated with unsafe sexual practices. School prevention programs must include drug use and sexuality topics simultaneously because both risk-taking behaviors occur simultaneously.

  16. Sexual behavior among high school students in Brazil: alcohol consumption and legal and illegal drug use associated with unprotected sex.

    Science.gov (United States)

    Sanchez, Zila M; Nappo, Solange A; Cruz, Joselaine I; Carlini, Elisaldo A; Carlini, Claudia M; Martins, Silvia S

    2013-04-01

    Alcohol and other drug use appears to reduce decision-making ability and increase the risk of unsafe sex, leading to possible unplanned pregnancies, sexually transmitted diseases/human immunodeficiency virus/HIV transmission, and multiple sexual partners. This study aimed to test the hypothesis that risky sexual behaviors among adolescents are associated with legal and illegal drug use. A national cross-sectional survey of 17,371 high-school students was conducted in 2010. Students were selected from 789 public and private schools in each of the 27 Brazilian state capitals by a multistage probabilistic sampling method and answered a self-report questionnaire. Weighted data were analyzed through basic contingency tables and logistic regressions testing for differences in condom use among adolescents who were sexually active during the past month. Approximately one third of the high school students had engaged in sexual intercourse in the month prior to the survey, and nearly half of these respondents had not used a condom. While overall sexual intercourse was more prevalent among boys, unsafe sexual intercourse was more prevalent among girls. Furthermore, a lower socioeconomic status was directly associated with non-condom use, while binge drinking and illegal drug use were independently associated with unsafe sexual intercourse. Adolescent alcohol and drug use were associated with unsafe sexual practices. School prevention programs must include drug use and sexuality topics simultaneously because both risk-taking behaviors occur simultaneously.

  17. The association between neighborhood socioeconomic disadvantage and high-risk injection behavior among people who inject drugs.

    Science.gov (United States)

    DeCuir, Jennifer; Lovasi, Gina S; El-Sayed, Abdulrahman; Lewis, Crystal Fuller

    2018-02-01

    Although much research has been conducted on the determinants of HIV risk behavior among people who inject drugs (PWID), the influence of the neighborhood context on high-risk injection behavior remains understudied. To address this gap in the literature, we measured associations between neighborhood socioeconomic disadvantage and high-risk injection behavior, and determined whether these associations were modified by drug-related police activity and syringe exchange program (SEP) accessibility. Our sample was comprised of 484 pharmacy-recruited PWID in New York City. Measures of neighborhood socioeconomic disadvantage were created using data from the 2006-2010 American Community Survey. Associations with high-risk injection behavior were estimated using multivariable Poisson regression. Effect modification by drug-related police activity and SEP accessibility was assessed by entering cross-product terms into adjusted models of high-risk injection behavior. Neighborhood socioeconomic disadvantage was associated with decreased receptive syringe sharing and unsterile syringe use. In neighborhoods with high drug-related police activity, associations between neighborhood disadvantage and unsterile syringe use were attenuated to the null. In neighborhoods with high SEP accessibility, neighborhood disadvantage was associated with decreased acquisition of syringes from an unsafe source. PWID in disadvantaged neighborhoods reported safer injection behaviors than their counterparts in neighborhoods that were relatively better off. The contrasting patterns of effect modification by SEP accessibility and drug-related police activity support the use of harm reduction approaches over law enforcement-based strategies for the control of blood borne virus transmission among PWID in disadvantaged urban areas. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Automated high-content live animal drug screening using C. elegans expressing the aggregation prone serpin α1-antitrypsin Z.

    Directory of Open Access Journals (Sweden)

    Sager J Gosai

    2010-11-01

    Full Text Available The development of preclinical models amenable to live animal bioactive compound screening is an attractive approach to discovering effective pharmacological therapies for disorders caused by misfolded and aggregation-prone proteins. In general, however, live animal drug screening is labor and resource intensive, and has been hampered by the lack of robust assay designs and high throughput work-flows. Based on their small size, tissue transparency and ease of cultivation, the use of C. elegans should obviate many of the technical impediments associated with live animal drug screening. Moreover, their genetic tractability and accomplished record for providing insights into the molecular and cellular basis of human disease, should make C. elegans an ideal model system for in vivo drug discovery campaigns. The goal of this study was to determine whether C. elegans could be adapted to high-throughput and high-content drug screening strategies analogous to those developed for cell-based systems. Using transgenic animals expressing fluorescently-tagged proteins, we first developed a high-quality, high-throughput work-flow utilizing an automated fluorescence microscopy platform with integrated image acquisition and data analysis modules to qualitatively assess different biological processes including, growth, tissue development, cell viability and autophagy. We next adapted this technology to conduct a small molecule screen and identified compounds that altered the intracellular accumulation of the human aggregation prone mutant that causes liver disease in α1-antitrypsin deficiency. This study provides powerful validation for advancement in preclinical drug discovery campaigns by screening live C. elegans modeling α1-antitrypsin deficiency and other complex disease phenotypes on high-content imaging platforms.

  19. Correlates of Marijuana Drugged Driving and Openness to Driving While High: Evidence from Colorado and Washington.

    Directory of Open Access Journals (Sweden)

    Kevin C Davis

    Full Text Available A potential unintended consequence of legalizing recreational marijuana is increased marijuana-related driving impairment. Some states where recreational marijuana is legal have begun implementing interventions to mitigate driving under the influence (DUI of marijuana, including media campaigns to increase knowledge about DUI laws. However, little is known about the associations between knowledge of DUI laws and marijuana DUI behavior. In this study, we provide new data from a survey of marijuana users in Colorado and Washington to examine associations between marijuana drugged driving and two potential behavioral precursors of marijuana DUI. We also explore other factors that may influence marijuana DUI.Data are from an online survey of marijuana users in Colorado and Washington. Respondents who reported any marijuana use in the past 30 days (n = 865 served as the analytic sample. We examined prevalence of two behavioral outcomes: (1 any driving of a motor vehicle while high in the past year and (2 driving a motor vehicle within 1 hour of using marijuana 5 or more times in the past month. Additional outcomes measuring willingness to drive while high were also assessed. Logistic regressions were used to estimate each outcome as a function of two multi-item scales measuring knowledge of the legal consequences of driving high and perceptions that driving while high is not safe. Additional covariates for potential confounders were included in each model.Prevalence of past-year driving while under the influence of marijuana was 43.6% among respondents. The prevalence of driving within 1 hour of using marijuana at least 5 times in the past month was 23.9%. Increased perception that driving high is unsafe was associated with lower odds of past-year marijuana DUI (OR = 0.31, P < 0.01 and lower past-month odds of driving 5 or more times within 1 hour of using marijuana (OR = 0.26, P < 0.01. Increased knowledge of marijuana DUI laws was also associated

  20. A spin labelling study of immunomodulating peptidoglycan monomer and adamantyltripeptides entrapped into liposomes.

    Science.gov (United States)

    Frkanec, Ruza; Noethig-Laslo, Vesna; Vranesić, Branka; Mirosavljević, Krunoslav; Tomasić, Jelka

    2003-04-01

    The interaction of immunostimulating compounds, the peptidoglycan monomer (PGM) and structurally related adamantyltripeptides (AdTP1 and AdTP2), respectively, with phospholipids in liposomal bilayers were investigated by electron paramagnetic resonance spectroscopy. (1). The fatty acids bearing the nitroxide spin label at different positions along the acyl chain were used to investigate the interaction of tested compounds with negatively charged multilamellar liposomes. Electron spin resonance (ESR) spectra were studied at 290 and 310 K. The entrapment of the adamantyltripeptides affected the motional properties of all spin labelled lipids, while the entrapment of PGM had no effect. (2). Spin labelled PGM was prepared and the novel compound bearing the spin label attached via the amino group of diaminopimelic acid was chromatographically purified and chemically characterized. The rotational correlation time of the spin labelled molecule dissolved in buffer at pH 7.4 was studied as a function of temperature. The conformational change was observed above 300 K. The same effect was observed with the spin labelled PGM incorporated into liposomes. Such effect was not observed when the spin labelled PGM was studied at alkaline pH, probably due to the hydrolysis of PGM molecule. The study of possible interaction with liposomal membrane is relevant to the use of tested compounds incorporated into liposomes, as adjuvants in vivo.

  1. Lactose hydrolysis by free and fibre-entrapped β-galactosidase from Streptococcus thermophilus

    Directory of Open Access Journals (Sweden)

    Zhennai Yang

    1993-09-01

    Full Text Available To study lactose hydrolysis by β-galactosidase, this enzyme was produced from Streptococcus thermophilus strain 11F and partially purified by acetone and ammonium sulphate fractionation, and ion exchange chromatography on a Q Sepharose FF column. Lactose hydrolysis by the enzyme was affected by lactose concentrations, sugars and milk proteins. The maximum extent of lactose hydrolysis in buffer was obtained with a 15% lactose concentration. Addition of 2% of lactose, glucose, galactose or sucrose in milk inhibited the enzymatic hydrolysis. The enzyme was activated by bovine serum albumin and a combination of αs-casein and β-casein. Of the casein fractions, the principal fraction, αs-casein, was less effective than β-casein and κ-casein. The fibre entrapped enzyme had a temperature optimum of 57°C, and a pH optimum from 7.5 to at least 9.0 with O-nitrophenyl-β-D-galactopyranoside as substrate. By recycling with whey and skim milk through a jacketed glass column (1.6 cm x 30 cm loaded with fibre-entrapped enzyme at 55°C, a lactose hydrolysis of 49.5% and 47.9% was achieved in 11 h and 7 h respectively.

  2. Effect of Air Gap Entrapped in Firefighter Protective Clothing on Thermal Resistance and Evaporative Resistance

    Directory of Open Access Journals (Sweden)

    He Hualing

    2018-03-01

    Full Text Available Heat and water vapor transfer behavior of thermal protective clothing is greatly influenced by the air gap entrapped in multilayer fabric system. In this study, a sweating hot plate method was used to investigate the effect of air gap position and size on thermal resistance and evaporative resistance of firefighter clothing under a range of ambient temperature and humidity. Results indicated that the presence of air gap in multilayer fabric system decreased heat and water vapor transfer abilities under normal wear. Moreover, the air gap position slightly influenced the thermal and evaporative performances of the firefighter clothing. In this study, the multilayer fabric system obtained the highest thermal resistance, when the air space was located at position B. Furthermore, the effect of ambient temperature on heat and water vapor transfer properties of the multilayer fabric system was also investigated in the presence of a specific air gap. It was indicated that ambient temperature did not influence the evaporative resistance of thermal protective clothing. A thermographic image was used to test the surface temperature of multilayer fabric system when an air gap was incorporated. These results suggested that a certain air gap entrapped in thermal protective clothing system could affect wear comfort.

  3. Comparison of the internalization of targeted dendrimers and dendrimer-entrapped gold nanoparticles into cancer cells.

    Science.gov (United States)

    Shi, Xiangyang; Wang, Su He; Lee, Inhan; Shen, Mingwu; Baker, James R

    2009-11-01

    Dendrimer-based nanotechnology significantly advances the area of targeted cancer imaging and therapy. Herein, we compared the difference of surface acetylated fluorescein isocyanate (FI) and folic acid (FA) modified generation 5 (G5) poly(amidoamine) dendrimers (G5.NHAc-FI-FA), and dendrimer-entrapped gold nanoparticles with similar modifications ([(Au(0))(51.2)-G5.NHAc-FI-FA]) in terms of their specific internalization to FA receptor (FAR)-overexpressing cancer cells. Confocal microscopic studies show that both G5.NHAc-FI-FA and [(Au(0))(51.2-)G5.NHAc-FI-FA] exhibit similar internalization kinetics regardless of the existence of Au nanoparticles (NPs). Molecular dynamics simulation of the two different nanostructures reveals that the surface area and the FA moiety distribution from the center of the geometry are slightly different. This slight difference may not be recognized by the FARs on the cell membrane, consequently leading to similar internalization kinetics. This study underlines the fact that metal or inorganic NPs entrapped within dendrimers interact with cells in a similar way to that of dendrimers lacking host NPs. 2009 Wiley Periodicals, Inc.

  4. Grain Entrapment Pressure on the Torso: Can You Breathe while Buried in Grain?

    Science.gov (United States)

    Moore, Kevin G; Jones, Carol L

    2017-04-26

    The pressure applied to the chest and back of a simulated grain entrapment victim was measured. Pressure sensors were attached to the chest and back of a manikin that was buried in grain in the vertical position. Measurements were made in four grain types at four grain depths ranging from the top of the manikin's shoulders to 0.61 m (24 in.) over the head. The pressure ranged from 1.6 to 4.0 kPa (0.23 to 0.57 psi). Based on available physiological information, this amount of pressure is unlikely to limit the respiration of an otherwise healthy adult male victim. However, other factors, such as the victim's age, gender, and body position in the grain, may influence respiration. The aspiration of grain appears to be the most likely asphyxiation risk during grain bin entrapment. Entering a grain storage bin is inherently dangerous, and Occupational Safety and Health Administration (OSHA) guidelines for permit-required confined spaces and grain handling facilities must be followed. Due to the risk of grain aspiration during engulfment, the development of safety equipment that could help protect the airway of a victim should be investigated. Copyright© by the American Society of Agricultural Engineers.

  5. Effects of cell entrapment in Ca-alginate on the metabolism of yeast Saccharomyces cerevisiae

    International Nuclear Information System (INIS)

    Galazzo, J.L.

    1989-01-01

    Saccharomyces cerevisiae cells grown in suspension have been immobilized in calcium-alginate beads. Fermentation rates and intracellular composition have been determined under nongrowing conditions in these Ca-alginate entrapped cells and for identical cells in suspension. Glucose uptake and ethanol and glycerol production are approximately two times faster in immobilized cells than in suspended cells. Intermediate metabolite levels such as fructose-1,6-diphosphate, glucose-6-phosphate and 3-phosphoglycerate have been determined by phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy under glucose fermenting conditions. Carbon-13 NMR shows an increase in polysaccharide production in immobilized cells. S. cerevisiae cells grown within a Ca-alginate matrix have a specific growth rate 40% lower than the growth rate of similar cells cultivated in suspension. Alginate-grown cells have been used to compare glucose fermentation under nongrowing conditions in suspended and Ca-entrapped cells. Fermentation rate is higher in immobilized cells than in suspended cells. The observed differences in intracellular components between suspended and immobilized cells are qualitatively similar to the differences observed for cells grown in suspension. Ethanol production rate is 2.7 times faster in immobilized alginate-grown cells than in suspended suspension-grown cells

  6. Anatomy of pudendal nerve at urogenital diaphragm--new critical site for nerve entrapment.

    Science.gov (United States)

    Hruby, Stephan; Ebmer, Johannes; Dellon, A Lee; Aszmann, Oskar C

    2005-11-01

    To investigate the relations of the pudendal nerve in this complex anatomic region and determine possible entrapment sites that are accessible for surgical decompression. Entrapment neuropathies of the pudendal nerve are an uncommon and, therefore, often overlooked or misdiagnosed clinical entity. The detailed relations of this nerve as it exits the pelvis through the urogenital diaphragm and enters the mobile part of the penis have not yet been studied. Detailed anatomic dissections were performed in 10 formalin preserved hemipelves under 3.5x loupe magnification. The pudendal nerve was dissected from the entrance into the Alcock canal to the dorsum of the penis. The branching pattern of the nerve and its topographic relationship were recorded and photographs taken. The anatomic dissections revealed that the pudendal nerve passes through a tight osteofibrotic canal just distal to the urogenital diaphragm at the entrance to the base of the penis. This canal is, in part, formed by the inferior ramus of the pubic bone, the suspensory ligament of the penis, and the ischiocavernous body. In two specimens, a fusiform pseudoneuromatous thickening was found. The pudendal nerve is susceptible to compression at the passage from the Alcock canal to the dorsum of the penis. Individuals exposed to repetitive mechanical irritation in this region are especially endangered. Diabetic patients with peripheral neuropathy can have additional compression neuropathy with decreased penile sensibility and will benefit from decompression of the pudendal nerve.

  7. Intractable Occipital Neuralgia Caused by an Entrapment in the Semispinalis Capitis

    Science.gov (United States)

    Kim, Deok-ryeong; Lee, Sang-won

    2013-01-01

    Occipital neuralgia is a rare pain syndrome characterized by periodic lancinating pain involving the occipital nerve complex. We present a unique case of entrapment of the greater occipital nerve (GON) within the semispinalis capitis, which was thought to be the cause of occipital neuralgia. A 66-year-old woman with refractory left occipital neuralgia revealed an abnormally low-loop of the left posterior inferior cerebellar artery on the magnetic resonance imaging, suggesting possible vascular compression of the upper cervical roots. During exploration, however, the GON was found to be entrapped at the perforation site of the semispinalis capitis. There was no other compression of the GON or of C1 and C2 dorsal roots in their intracranial course. Postoperatively, the patient experienced almost complete relief of typical neuralgic pain. Although occipital neuralgia has been reported to occur by stretching of the GON by inferior oblique muscle or C1-C2 arthrosis, peripheral compression in the transmuscular course of the GON in the semispinalis capitis as a cause of refractory occipital neuralgia has not been reported and this should be considered when assessing surgical options for refractory occipital neuralgia. PMID:24278663

  8. Solution-mediated growth of NBA-ZSM-5 crystals retarded by gel entrapment

    Science.gov (United States)

    Aguilar-Mamani, Wilson; Akhtar, Farid; Hedlund, Jonas; Mouzon, Johanne

    2018-04-01

    The synthesis of flat tablet-shaped ZSM-5 crystals from a gel using metakaolin as aluminosilicate source and n-butyl amine as structure directing agent was investigated. The evolution inside the solid phase was characterized by X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy, thermogravimetry and mass spectrometry. A kinetic study indicated that the nucleation of the majority crystals occurred concurrently with the formation of the gel upon heating the starting liquid suspension. Microstructural evidences undeniably showed that the gel precipitated on ZSM-5 crystals and mineral impurities originating from kaolin. As a result, crystal growth was retarded by gel entrapment, as indicated by the configuration and morphology of the embedded crystals. The results presented herein are harmonized with a solution-mediated nucleation and growth mechanism. Our observations differ from the autocatalytic model that suggests that the nuclei rest inside the gel until released when the gel is consumed. Our results show instead that it is crystals that formed in an early stage before entrapment inside the gel that rest inside the gel until exposed at the gel surface. These results illustrate the limitation of the classical method used in the field to determine nucleation profiles when the crystals become trapped inside the gel.

  9. High-Performance Signal Detection for Adverse Drug Events using MapReduce Paradigm.

    Science.gov (United States)

    Fan, Kai; Sun, Xingzhi; Tao, Ying; Xu, Linhao; Wang, Chen; Mao, Xianling; Peng, Bo; Pan, Yue

    2010-11-13

    Post-marketing pharmacovigilance is important for public health, as many Adverse Drug Events (ADEs) are unknown when those drugs were approved for marketing. However, due to the large number of reported drugs and drug combinations, detecting ADE signals by mining these reports is becoming a challenging task in terms of computational complexity. Recently, a parallel programming model, MapReduce has been introduced by Google to support large-scale data intensive applications. In this study, we proposed a MapReduce-based algorithm, for common ADE detection approach, Proportional Reporting Ratio (PRR), and tested it in mining spontaneous ADE reports from FDA. The purpose is to investigate the possibility of using MapReduce principle to speed up biomedical data mining tasks using this pharmacovigilance case as one specific example. The results demonstrated that MapReduce programming model could improve the performance of common signal detection algorithm for pharmacovigilance in a distributed computation environment at approximately liner speedup rates.

  10. Systematic review of available evidence on 11 high-priced inpatient orphan drugs

    NARCIS (Netherlands)

    T.A. Kanters (Tim A.); C. de Sonneville (Caroline); W.K. Redekop (Ken); L. van Hakkaart-van Roijen (Leona)

    2013-01-01

    markdownabstract__Abstract__ __Background__: Attention for Evidence Based Medicine (EBM) is growing, but evidence for orphan drugs is argued to be limited and inferior. This study systematically reviews the available evidence on clinical effectiveness, costeffectiveness and budget impact for

  11. Implementing an Alcohol and Other Drug Use Prevention Program Using University-High School Partnerships: Challenges and Lessons Learned

    Science.gov (United States)

    Milroy, Jeffrey J.; Orsini, Muhsin Michael; Wyrick, David L.; Fearnow-Kenney, Melodie; Wagoner, Kimberly G.; Caldwell, Rebecca

    2015-01-01

    Background: School-based alcohol and other drug use prevention remains an important national strategy. Collaborative partnerships between universities and high schools have the potential to enhance prevention programming; however, there are challenges to sustaining such partnerships. Purpose: The purpose of this commentary is to underscore…

  12. High-Throughput Lipolysis in 96-Well Plates for Rapid Screening of Lipid-Based Drug Delivery Systems

    DEFF Research Database (Denmark)

    Mosgaard, Mette D; Sassene, Philip J; Mu, Huiling

    2017-01-01

    The high-throughput in vitro intestinal lipolysis model (HTP) applicable for rapid and low-scale screening of lipid-based drug delivery systems (LbDDSs) was optimized and adjusted as to be conducted in 96-well plates (HTP-96). Three different LbDDSs (I-III) loaded with danazol or cinnarizine were...

  13. [The role of CCLINs in the event of an epidemic of multi-drug and highly resistant bacteria].

    Science.gov (United States)

    Landriu, Danièle

    2015-01-01

    The management of epidemics of multi-drug and highly resistant bacteria must be based on a structured organisation. Within each region it requires the expertise of centres for the interregional coordination of nosocomial infection control (CCLINs) and their regional branches of nosocomial infection control (Arlin) which support hospitals in reporting these types of epidemics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  14. The Effect of Parenting Stress on Child Behavior Problems in High-Risk Children with Prenatal Drug Exposure

    Science.gov (United States)

    Bagner, Daniel M.; Sheinkopf, Stephen J.; Miller-Loncar, Cynthia; LaGasse, Linda L.; Lester, Barry M.; Liu, Jing; Bauer, Charles R.; Shankaran, Seetha; Bada, Henrietta; Das, Abhik

    2009-01-01

    Objective: To examine the relationship between early parenting stress and later child behavior in a high-risk sample and measure the effect of drug exposure on the relationship between parenting stress and child behavior. Methods: A subset of child-caregiver dyads (n = 607) were selected from the Maternal Lifestyle Study (MLS), which is a large…

  15. [Survey on junior high school student's attitudes toward rational drug use and the educational effect by school pharmacists].

    Science.gov (United States)

    Yamada, Junichi; Takayanagi, Risa; Yokoyama, Haruko; Suzuki, Yasuhiro; Sinohara, Satomi; Yamada, Yasuhiko

    2012-01-01

    The educational intervention could improve knowledge about rational drug use in the junior high school. Improving knowledge about rational drug use at an early age may be a good way to increase the population's awareness of health, medicines and self-medication. To educate the rational drug use, it is desirable that the school pharmacists participate in this educational program in the junior high school. So we conducted an educational lecture by school pharmacists to promote rational drug use and self-medication in junior high school students. The study compared participant responses before and after a lecture. After the first questionnaire, we lectured the mentioned above to them. Afterward, second questionnaire was conducted. In the second questionnaire, more than 95% of the students understood the contents of the lecture to some extent. After a lecture, students who answered that 'I don't have confidence that I can buy medicines rightly by myself' decreased from 42.7% to 11.7%. And students who answered that 'I don't have confidence that I can use medicines rightly by myself' decreased from 25.2% to 12.6%. It was possible to achieve a favorable modification of attitudes to rational use of medicines in junior high school students. Continuous interventions might allow better effects and could help to fill the gap in health education of the general population.

  16. Design and characterisation of matrix tablets of highly water soluble drug

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Prakya

    2012-04-01

    Full Text Available Tramadol HCL is a centrally acting opioid analgesic. Although the drug has a higher plasma half life, the steady state plasma concentration is not achieved with frequent dosing of q.i.d at 6 hour intervals. Therefore, the objective of the present work was to formulate a 100mg strength Tramadol matrix tablets to extend the drug release and thus decrease the dosing frequency and achieve steady state plasma concentration. Initially, preformulation studies were carried out to rule out any incompatibility between the drug and the chosen polymer(s after exposing physical mixtures of the drug and the polymer(s to 40 and deg;C/75% RH for three months. A suitable method was developed for drug estimation at 271nm by a UV double beam spectrophotometer. Next, various batches of tablets were designed using different polymers such as Ethylcellulose, Carnauba wax, HPMC-K100M, Carbopol-974P and Kollidon-SR. Direct compression technique was used except for the formulation containing carnauba wax for which melt granulation was done followed by compression. Formulations F-1 to F-15 contained single polymers in increasing concentrations in drug:polymer ratios of 1:1, 1:2 and 1:3 where it was observed that the drug release extended with increasing polymer concentrations. Carbopol-974P extended drug release better followed by HPMC-K100M and Carnauba wax compared to other polymers. A combination of these polymers was also used at various ratios to get formulations F-16 to F-20 and observed that the polymer combinations controlled drug release better. The type of fillers like lactose and microcrystalline cellulose had no effect on the physiochemical characters as well as on the drug release profiles. The in vitro release data from the best formulation fitted well in Higuchi as well as Peppas model, the and #8216;n and #8217; value, which confirmed that the release mechanism shifted from initial dissolution to later extended diffusion in which both diffusion and erosion

  17. A lyophilized etoposide submicron emulsion with a high drug loading for intravenous injection: preparation, evaluation, and pharmacokinetics in rats.

    Science.gov (United States)

    Chen, Hao; Shi, Shuai; Zhao, Mingming; Zhang, Ling; He, Haibing; Tang, Xing

    2010-12-01

    To develop a submicron emulsion for etoposide with a high drug loading capacity using a drug-phospholipid complex combined with drug freeze-drying techniques. An etoposide-phospholipid complex (EPC) was prepared and its structure was confirmed by X-ray diffraction and differential scanning calorimetry analysis. A freeze-drying technique was used to produce lyophilized etoposide emulsions (LEPE), and LEPE was investigated with regard to their appearance, particle size, and zeta potential. The pharmacokinetic study in vivo was determined by the UPLC/MS/MS system. It showed that EPC significantly improved the liposolubility of etoposide, indicating a high drug loading intravenous emulsion could be easily prepared by EPC. Moreover, the obtained loading of etoposide in the submicron emulsion was 3.0 mg/mL, which was three times higher than that of the previous liquid emulsions. The optimum cryoprotectant was trehalose (15%) in freeze-drying test. The median diameter, polydispersity index, and zeta potential of the optimum formulation of LEPE were 226.1 ± 5.1 nm, 0.107 ± 0.011, and -36.20 ± 1.13 mV, respectively. In addition, these parameters had no significant change during 6 months storage at 4 ± 2°C. The main pharmacokinetic parameters exhibited no significant differences between LEPE and etoposide commercial solution except for area under the concentration-time curve and clearance. The stable etoposide emulsion with a high drug loading was successfully prepared, indicating the amount of excipients such as the oil phase and emulsifiers significantly decreased following administration of the same dose of drug, effectively reducing the metabolism by patients while increasing their compliance. Therefore, LEPE has a great potential for clinical applications.

  18. Examining the Acceptability of mHealth Technology in HIV Prevention Among High-Risk Drug Users in Treatment.

    Science.gov (United States)

    Shrestha, Roman; Huedo-Medina, Tania B; Altice, Frederick L; Krishnan, Archana; Copenhaver, Michael

    2017-11-01

    Despite promising trends of the efficacy of mobile health (mHealth) based strategies to a broad range of health conditions, very few if any studies have been done in terms of the examining the use of mHealth in HIV prevention efforts among people who use drugs in treatment. Thus, the goal of this study was to gain insight into the real-world acceptance of mHealth approaches among high-risk people who use drugs in treatment. A convenience sample of 400 HIV-negative drug users, who reported drug- and/or sex-related risk behaviors, were recruited from a methadone clinic in New Haven, Connecticut. Participants completed standardized assessments of drug- and sex-related risk behaviors, neurocognitive impairment (NCI), and measures of communication technology access and utilization, and mHealth acceptance. We found a high prevalence of current ownership and use of mobile technologies, such as cell phone (91.5%) including smartphone (63.5%). Participants used mobile technologies to communicate mostly through phone calls (M = 4.25, SD = 1.24), followed by text messages (M = 4.21, SD = 1.29). Participants expressed interest in using mHealth for medication reminders (72.3%), receive information about HIV (65.8%), and to assess drug-related (72.3%) and sex-related behaviors (64.8%). Furthermore, participants who were neurocognitively impaired were more likely to use cell phone without internet and show considerable interest in using mHealth as compared to those without NCI. The findings from this study provide empirical evidence that mHealth-based programs, specifically cell phone text messaging-based health programs, may be acceptable to this high-risk population.

  19. Management of Hypercholesterolemia, Appropriateness of Therapeutic Approaches and New Drugs in Patients with High Cardiovascular Risk.

    Science.gov (United States)

    Agabiti Rosei, Enrico; Salvetti, Massimo

    2016-09-01

    Control of lipid levels is one of the most effective strategies for cardiovascular (CV) event prevention. In fact, many clinical trials have clearly demonstrated that low-density lipoprotein cholesterol (LDL-C) lowering, primarily with statins, reduces major CV events and mortality. The evidence from these trials has been useful in designing the cholesterol treatment guidelines, which are mainly aimed at preventing and managing cardiovascular disease (CVD). However, available data indicate that a large proportion of patients fail to achieve lipid goals, and this is particularly frequent in patients at high or very high CV risk. Furthermore, owing to side effects, a significant percentage of patients cannot tolerate statin treatment. Hence, researchers have focused their attention on novel LDL-C-lowering agents that act via mechanisms distinct from that of statins. Among the new compounds under investigation, the monoclonal antibodies to proprotein convertase subtilisin/kexin type 9 (PCSK9) seem particularly promising, having recently been shown to be well tolerated and highly effective at lowering LDL-C, with a possible effect on the occurrence of CV events. Currently, alirocumab is approved by the US Food and Drug Administration (FDA) as an adjunct to diet and maximally tolerated statin therapy for use in adults with heterozygous familial hypercholesterolemia (FH) or those with atherosclerotic CV disease who require additional LDL-C lowering; it has also been recently approved by the European Medicines Agency (EMA) for use in patients with heterozygous FH, non-familial hypercholesterolemia or mixed dyslipidemia in whom statins are ineffective or not tolerated. Evolocumab is approved by the FDA as an adjunct to diet and maximally tolerated statins for adults with hetero- and homozygous FH and those with atherosclerotic CV disease who require additional lowering of LDL-C, and by the EMA in adults with primary hypercholesterolemia or mixed dyslipidemia, as an adjunct

  20. Intravascular ultrasound as a novel tool for the diagnosis and targeted treatment of functional popliteal artery entrapment syndrome

    Directory of Open Access Journals (Sweden)

    Anna E. Boniakowski, MD

    2017-06-01

    Full Text Available Functional popliteal artery entrapment syndrome can be difficult to diagnose, as the imaging modalities presently employed are designed to detect anatomic entrapment. We describe a novel imaging technique to aid in diagnosis in this cohort. A 22-year-old cyclist presented with exercise-limiting claudication. Magnetic resonance angiography with provocative maneuvers was nondiagnostic. Digital subtraction angiography revealed long-segment occlusion of the popliteal artery with plantar flexion; however, the specific site of compression remained unclear. Intravascular ultrasound allowed specific localization of compression and further confirmed the diagnosis. Thus, we report this as an adjunctive imaging modality to definitively diagnose functional popliteal artery entrapment syndrome and to assist in operative planning.

  1. High-throughput screen of drug repurposing library identifies inhibitors of Sarcocystis neurona growth.

    Science.gov (United States)

    Bowden, Gregory D; Land, Kirkwood M; O'Connor, Roberta M; Fritz, Heather M

    2018-04-01

    The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are 60-70% effective. Advancement of treatment requires new technology to identify new drugs for EPM. To address this critical need, we developed, validated, and implemented a high-throughput screen to test 725 FDA-approved compounds from the NIH clinical collections library for anti-S. neurona activity. Our screen identified 18 compounds with confirmed inhibitory activity against S. neurona growth, including compounds active in the nM concentration range. Many identified inhibitory compounds have well-defined mechanisms of action, making them useful tools to study parasite biology in addition to being potential therapeutic agents. In comparing the activity of inhibitory compounds identified by our screen to that of other screens against other apicomplexan parasites, we found that most compounds (15/18; 83%) have activity against one or more related apicomplexans. Interestingly, nearly half (44%; 8/18) of the inhibitory compounds have reported activity against dopamine receptors. We also found that dantrolene, a compound already formulated for horses with a peak plasma concentration of 37.8 ± 12.8 ng/ml after 500 mg dose, inhibits S. neurona parasites at low concentrations (0.065 μM [0.036-0.12; 95% CI] or 21.9 ng/ml [12.1-40.3; 95% CI]). These studies demonstrate the use of a new tool for discovering new chemotherapeutic agents for EPM and potentially providing new reagents to elucidate biologic pathways required for successful S. neurona infection. Copyright © 2018. Published by Elsevier Ltd.

  2. Unraveling Mycobacterium tuberculosis genomic diversity and evolution in Lisbon, Portugal, a highly drug