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Sample records for high drug concentration

  1. Spectrophotometric Method for the Determination of Two Coformulated Drugs with Highly Different Concentrations. Application on Vildagliptin and Metformin Hydrochloride

    Science.gov (United States)

    Zaazaa, H. E.; Elzanfaly, E. S.; Soudi, A. T.; Salem, M. Y.

    2016-03-01

    A new smart simple validated spectrophotometric method was developed for the determination of two drugs one of which is in a very low concentration compared to the other. The method is based on spiking and dilution then simple mathematical manipulation of the absorbance spectra. This method was applied for the determination of a binary mixture of vildagliptin and metformin hydrochloride in the ratio 50:850 in laboratory prepared mixtures containing both drugs in this ratio and in pharmaceutical dosage form with good recoveries. The developed method was validated according to ICH guidelines and can be used for routine quality control testing.

  2. Green Pharmaceutical Analysis of Drugs Coformulated with Highly Different Concentrations Using Spiking and Manipulation of Their Ratio Spectra.

    Science.gov (United States)

    Ayoub, Bassam M

    2017-07-01

    Introducing green analysis to pharmaceutical products is considered a significant approach to preserving the environment. This method can be an environmentally friendly alternative to the existing methods, accompanied by a validated automated procedure for the analysis of a drug with the lowest possible number of samples. Different simple spectrophotometric methods were developed for the simultaneous determination of empagliflozin (EG) and metformin (MT) by manipulating their ratio spectra in their application on a recently approved pharmaceutical combination, Synjardy tablets. A spiking technique was used to increase the concentration of EG in samples prepared from the tablets to allow for the simultaneous determination of EG with MT without prior separation. Validation parameters according to International Conference on Harmonization guidelines were acceptable over a concentration range of 2-12 μg/mL for both drugs using derivative ratio and ratio subtraction coupled with extended ratio subtraction. The optimized methods were compared using one-way analysis of variance and proved to be suitable as ecofriendly approaches for industrial QC laboratories.

  3. Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Hsu YH

    2014-09-01

    Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

  4. Highly concentrating Fresnel lenses

    International Nuclear Information System (INIS)

    Kritchman, E.M.; Friesem, A.A.; Yekutieli, G.

    1979-01-01

    A new type of concave Fresnel lens capable of concentrating solar radiation very near the ultimate concentration limit is considered. The differential equations that describe the lens are solved to provide computed solutions which are then checked by ray tracing techniques. The performance (efficiency and concentration) of the lens is investigated and compared to that of a flat Fresnel lens, showing that the new lens is preferable for concentrating solar radiation. (author)

  5. Ultra flat ideal concentrators of high concentration

    Energy Technology Data Exchange (ETDEWEB)

    Chaves, Julio [IST, Physics Dept., Lisboa (Portugal); INETI-DER, Lisboa (Portugal); Collares-Pereira, Manuel [INETI-DER, Lisboa (Portugal)

    2000-07-01

    A new method for the design of nonimaging devices is presented. Its application to the design of ultra flat compact concentrators is analysed. These new concentrators are based on a combination of two stages: the first one is composed of a large number of small structures placed side by side and the second one is a very compact single device concentrating the radiation to the limit. These devices are ideal for 2D. These compact designs are much more compact than the traditional ones like lens-mirror combinations or parabolic primaries with nonimaging secondaries. Besides, they can be designed for any acceptance angle, while the traditional ones are limited to small acceptance angles. (Author)

  6. Determination of the total concentration of highly protein-bound drugs in plasma by on-line dialysis and column liquid chromatography: application to non-steroidal anti-inflammatory drugs.

    NARCIS (Netherlands)

    Herraez-Hernandez, R.; van de Merbel, N.C.; Brinkman, U.A.T.

    1995-01-01

    The potential of on-line dialysis as a sample preparation procedure for compounds highly bound to plasma proteins is evaluated, using non-steroidal anti-inflammatory drugs as model compounds and column liquid chromatography as the separation technique. Different strategies to reduce the degree of

  7. Determination of the total concentration of highly protein-bound drugs in plasma by on-line dialysis and column liquid chromatography : application to non-steroidal anti-inflammatory drugs

    NARCIS (Netherlands)

    Herráez-Hernández, R; van de Merbel, N C; Brinkman, U A

    1995-01-01

    The potential of on-line dialysis as a sample preparation procedure for compounds highly bound to plasma proteins is evaluated, using non-steroidal anti-inflammatory drugs as model compounds and column liquid chromatography as the separation technique. Different strategies to reduce the degree of

  8. High concentration agglomerate dynamics at high temperatures.

    Science.gov (United States)

    Heine, M C; Pratsinis, S E

    2006-11-21

    The dynamics of agglomerate aerosols are investigated at high solids concentrations that are typical in industrial scale manufacture of fine particles (precursor mole fraction larger than 10 mol %). In particular, formation and growth of fumed silica at such concentrations by chemical reaction, coagulation, and sintering is simulated at nonisothermal conditions and compared to limited experimental data and commercial product specifications. Using recent chemical kinetics for silica formation by SiCl4 hydrolysis and neglecting aerosol polydispersity, the evolution of the diameter of primary particles (specific surface area, SSA), hard- and soft-agglomerates, along with agglomerate effective volume fraction (volume occupied by agglomerate) is investigated. Classic Smoluchowski theory is fundamentally limited for description of soft-agglomerate Brownian coagulation at high solids concentrations. In fact, these high concentrations affect little the primary particle diameter (or SSA) but dominate the soft-agglomerate diameter, structure, and volume fraction, leading to gelation consistent with experimental data. This indicates that restructuring and fragmentation should affect product particle characteristics during high-temperature synthesis of nanostructured particles at high concentrations in aerosol flow reactors.

  9. Using Potentiometric Free Drug Sensors to Determine the Free Concentration of Ionizable Drugs in Colloidal Systems

    DEFF Research Database (Denmark)

    Tran, Thuy; Chakraborty, Anjan; Xi, Xi

    2018-01-01

    The present study investigates the use of free drug sensors (FDS) to measure free ionized drug concentrations in colloidal systems, including micellar solutions, emulsions, and lipid formulations during in vitro lipolysis. Diphenhydramine hydrochloride (DPH) and loperamide hydrochloride (LOP) wer...

  10. Urine Creatinine Concentrations in Drug Monitoring Participants and Hospitalized Patients.

    Science.gov (United States)

    Love, Sara A; Seegmiller, Jesse C; Kloss, Julie; Apple, Fred S

    2016-10-01

    Urine drug testing is commonly performed in both clinical and forensic arenas for screening, monitoring and compliance purposes. We sought to determine if urine creatinine concentrations in monitoring program participants were significantly different from hospital in-patients and out-patients undergoing urine drug testing. We retrospectively reviewed urine creatinine submitted in June through December 2015 for all specimens undergoing urine drug testing. The 20,479 creatinine results were categorized as hospitalized patients (H) and monitoring/compliance groups for pain management (P), legal (L) or recovery (R). Median creatinine concentrations (interquartile range, mg/dL) were significantly different (P creatinine concentrations were significantly lower in the R vs. L group (Pcreatinine concentration and may indicate participants' attempts to tamper with their drug test results through dilution means. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  11. Influence of drug concentration on the diffusion parameters of caffeine

    Science.gov (United States)

    Mustapha, R.Ben; Lafforgue, C.; Fenina, N.; Marty, J.P.

    2011-01-01

    Background and Objectives: In the fields of the pharmaceutical and cosmetic industries and in toxicology, the study of the skin penetration of molecules is very interesting. Various studies have considered the impact of different physicochemical drug characteristics, skin thickness, and formulations, on the transition from the surface of the skin to the underlying tissues or to the systemic circulation; however, the influence of drug concentration on the permeation flux of molecules has rarely been raised. Our study aims to discover the influence of caffeine concentration in a formulation on the percutaneous penetration from gels, as a result of different dose applications to polysulfate membrane and human skin. Materials and Methods: For this purpose, three identical base gels were used at 1, 3, and 5% of caffeine, to evaluate the effect of the concentration of caffeine on in vitro release through the synthetic membrane and ex vivo permeation through the human skin, using diffusion FranzTM cells. Results: The diffusion through the epidermal tissue was significantly slower than through the synthetic membrane, which recorded an increase of flux with an increase in the concentration of caffeine. The skin permeation study showed that diffusion depended not only on the concentration, but also on the deposited amount of gel. Nevertheless, for the same amount of caffeine applied, the flux was more significant from the less concentrated gel. Conclusion: Among all the different concentrations of caffeine examined, 1% gel of caffeine applied at 5 mg / cm2 showed the highest absorption characteristics across human skin. PMID:21572649

  12. Suspended particle and drug ingredient concentrations in hospital dispensaries and implications for pharmacists' working environments.

    Science.gov (United States)

    Inaba, Ryoichi; Hioki, Atsushi; Kondo, Yoshihiro; Nakamura, Hiroki; Nakamura, Mitsuhiro

    2016-03-01

    The aim of this study was to assess the present status of working environments for pharmacists, including the concentrations of suspended particles and suspended drug ingredients in dispensaries. We conducted a survey on the work processes and working environment in 15 hospital dispensaries, and measured the concentrations of suspended particles and suspended drug ingredients using digital dust counter and high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS), respectively. Of 25 types of powdered drugs that were frequently handled in the 15 dispensaries surveyed, 11 could be quantitatively determined. The amounts of suspended particles were relatively high, but below the reference value, in three dispensaries without dust collectors. The sedative-hypnotic drug zopiclone was detected in the suspended particles at one dispensary that was not equipped with dust collectors, and the antipyretic and analgesic drug acetaminophen was detected in two dispensaries equipped with dust collectors. There was no correlation between the daily number of prescriptions containing powdered drugs and the concentration of suspended particles in dispensaries. On the basis of the suspended particle concentrations measured, we concluded that dust collectors were effective in these dispensaries. However, suspended drug ingredients were detected also in dispensaries with dust collectors. These results suggest that the drug dust control systems of individual dispensaries should be properly installed and managed.

  13. Serum magnesium concentration in drug-addicted patients.

    Science.gov (United States)

    Karakiewicz, Beata; Kozielec, Tadeusz; Brodowski, Jacek; Chlubek, Dariusz; Noceń, Iwona; Starczewski, Andrzej; Brodowska, Agnieszka; Laszczyńska, Maria

    2007-03-01

    Drug addiction is a complex problem which leads to many somatic, psychic and social diseases. It is accompanied by the disturbed metabolism of various macro and micronutrients. The aim of this study was to assess serum magnesium concentration in drug-addicted patients and analyze whether Human Immunodeficiency Virus (HIV) infection and methadone treatment affect the level of serum magnesium in these patients. The examination was conducted in a group of 83 people - patients of Szczecin-Zdroje Psychiatric Hospital (Poland). They were 21 to 49 years old, and the mean age was 32 +/- 7 years. The control group consisted of 81 healthy individuals. Flame atomic-absorption spectrometry method was used to determine the magnesium concentration. The total serum magnesium concentration was calculated for the whole patient group, subgroups of women and men, a subgroup of people infected with HIV, and a subgroup receiving methadone substitution treatment. How magnesium behaves depending on age and addiction period, was checked. The mean concentration of magnesium in blood serum of the patients examined was 0.57 mmol/L, which was significantly lower than in the control group. In the subgroup of men it was 0.57 mmol/L, and in the subgroup of women - 0.55 mmol/L; the differences were not statistically significant. In the patient group nobody had the appropriate magnesium concentration in blood serum. No significant correlation was found between the magnesium concentration, age of the patients and addiction period. In the subgroup of seropositive people the mean concentration of magnesium was 0.55 mmol/L, and in the subgroup of non-infected patients - 0.58 mmol/L; the difference was not statistically significant. The mean concentration of magnesium in the subgroup treated with methadone was 0.59 mmol/L, and in the subgroup not involved in this type of therapy - 0.55 mmol/L; it was not a statistically significant difference.

  14. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François, E-mail: francois.marceau@crchul.ulaval.ca

    2013-07-15

    Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K{sub M} 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V{sub max}. PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion

  15. High affinity capture and concentration of quinacrine in polymorphonuclear neutrophils via vacuolar ATPase-mediated ion trapping: Comparison with other peripheral blood leukocytes and implications for the distribution of cationic drugs

    International Nuclear Information System (INIS)

    Roy, Caroline; Gagné, Valérie; Fernandes, Maria J.G.; Marceau, François

    2013-01-01

    Many cationic drugs are concentrated in acidic cell compartments due to low retro-diffusion of the protonated molecule (ion trapping), with an ensuing vacuolar and autophagic cytopathology. In solid tissues, there is evidence that phagocytic cells, e.g., histiocytes, preferentially concentrate cationic drugs. We hypothesized that peripheral blood leukocytes could differentially take up a fluorescent model cation, quinacrine, depending on their phagocytic competence. Quinacrine transport parameters were determined in purified or total leukocyte suspensions at 37 °C. Purified polymorphonuclear leukocytes (PMNLs, essentially neutrophils) exhibited a quinacrine uptake velocity inferior to that of lymphocytes, but a consistently higher affinity (apparent K M 1.1 vs. 6.3 μM, respectively). However, the vacuolar (V)-ATPase inhibitor bafilomycin A1 prevented quinacrine transport or initiated its release in either cell type. PMNLs capture most of the quinacrine added at low concentrations to fresh peripheral blood leukocytes compared with lymphocytes and monocytes (cytofluorometry). Accumulation of the autophagy marker LC3-II occurred rapidly and at low drug concentrations in quinacrine-treated PMNLs (significant at ≥ 2.5 μM, ≥ 2 h). Lymphocytes contained more LAMP1 than PMNLs, suggesting that the mass of lysosomes and late endosomes is a determinant of quinacrine uptake V max . PMNLs, however, exhibited the highest capacity for pinocytosis (uptake of fluorescent dextran into endosomes). The selectivity of quinacrine distribution in peripheral blood leukocytes may be determined by the collaboration of a non-concentrating plasma membrane transport mechanism, tentatively identified as pinocytosis in PMNLs, with V-ATPase-mediated concentration. Intracellular reservoirs of cationic drugs are a potential source of toxicity (e.g., loss of lysosomal function in phagocytes). - Highlights: • Quinacrine is concentrated in acidic organelles via V-ATPase-mediated ion trapping

  16. An introduction to predictive modelling of drug concentration in anaesthesia monitors.

    Science.gov (United States)

    DeCou, J; Johnson, K

    2017-01-01

    A significant amount of anaesthetists' work involves the prediction of drug effects and interactions to produce a smooth general anaesthetic that minimises drug side effects and promotes rapid emergence. Successfully managing this process requires a basic understanding of drug effects, experience and inevitably some guesswork, since it is difficult (and in some cases impossible) to anticipate all relevant patient and surgical factors. Although data are generally available to allow calculation of plasma drug and effect site concentrations, this is often difficult to apply in complex clinical contexts, particularly when multiple drug types are used. In recent years, manufacturers have developed and incorporated into anaesthetic workstations technologies that use drug pharmacodynamic and pharmacokinetic data to predict drug effects and interactions. Such systems can predict the duration and effects of drugs during anaesthesia and assist the anaesthetist to understand complex drug interactions. With this information available, different drug types, doses and combinations may be tailored in a scientific way to maximise useful effects whilst minimising overdose and side-effects, particularly in high-risk patients. Examples are used to illustrate how such systems can be used in practice, and how drug effects and interactions can be simulated to "rehearse" an anaesthetic before any drugs are actually administered. At present only a small number of anaesthetic workstations use this technology, and as yet they are not able to manage all drugs used in anaesthetic practice. However, such systems have the potential to help anaesthetists manage the complexity of their work, and to provide information on predicted drug effects in a way that is useful and relevant to both experienced anaesthetists and trainees. © 2017 The Association of Anaesthetists of Great Britain and Ireland.

  17. Anticancer drugs in Portuguese surface waters - Estimation of concentrations and identification of potentially priority drugs.

    Science.gov (United States)

    Santos, Mónica S F; Franquet-Griell, Helena; Lacorte, Silvia; Madeira, Luis M; Alves, Arminda

    2017-10-01

    Anticancer drugs, used in chemotherapy, have emerged as new water contaminants due to their increasing consumption trends and poor elimination efficiency in conventional water treatment processes. As a result, anticancer drugs have been reported in surface and even drinking waters, posing the environment and human health at risk. However, the occurrence and distribution of anticancer drugs depend on the area studied and the hydrological dynamics, which determine the risk towards the environment. The main objective of the present study was to evaluate the risk of anticancer drugs in Portugal. This work includes an extensive analysis of the consumption trends of 171 anticancer drugs, sold or dispensed in Portugal between 2007 and 2015. The consumption data was processed aiming at the estimation of predicted environmental loads of anticancer drugs and 11 compounds were identified as potentially priority drugs based on an exposure-based approach (PEC b > 10 ng L -1 and/or PEC c > 1 ng L -1 ). In a national perspective, mycophenolic acid and mycophenolate mofetil are suspected to pose high risk to aquatic biota. Moderate and low risk was also associated to cyclophosphamide and bicalutamide exposition, respectively. Although no evidences of risk exist yet for the other anticancer drugs, concerns may be associated with long term effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Characterization of high concentration dust generator

    International Nuclear Information System (INIS)

    Shimura, Toichiro; Yokochi, Akira

    1999-01-01

    This paper describes the development of fluidized bed type high concentration dust generator that keeps for long period dust concentration range of about 10 mg/m 3 for the study of working place monitoring system and evaluation of respirator. The generator is keeping constant powder in fluidized bed for keeping the dust concentration. It is necessary to keep constant feeding rate of powder in order to keep the quantity of dust in the fluidized bed. Our generator enables to obtain constant feeding rate by a screw feeder and by using mixed powder with fluidising particles (glass beads) before feeding. The generator produces high concentration dust of 11.3 mg/m 3 ± 1.0 mg/m 3 for about 5 hours and keeps the dust size 4.2-4.6 μm in mass median aerodynamic diameter with reasonable reproducibility. (author)

  19. Stress concentration effects in high pressure components

    International Nuclear Information System (INIS)

    Aller, J.E.

    1990-01-01

    This paper examines the stress concentration effects of sideholes in thick walled, high pressure cylinders. It has been shown that the theoretical stress concentration factor at the intersection of a small crossbore in a closed end, thick walled cylinder varies between 3.0 and 4.0. Tests have shown that this effect can be greatly reduced in practice by carefully radiusing the bore intersection and autofrettaging the cylinder. It has also been shown that the minimum stress concentration factor occurs when the main bore and sidehole or crossbore have the same diameter, and the radius of the intersection is approximately equal to the sidehole radius. When the bore and sidehole intersection angle decreases from 90 degrees, the stress concentration factor increases significantly. Knowledge of these fundamental relationships can be used in maintaining, as well ad designing, high pressure equipment

  20. [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.

  1. 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.

  2. Cellulase Inhibition by High Concentrations of Monosaccharides

    DEFF Research Database (Denmark)

    Hsieh, Chia-Wen; Cannella, David; Jørgensen, Henning

    2014-01-01

    Biological degradation of biomass on an industrial scale culminates in high concentrations of end products. It is known that the accumulation of glucose and cellobiose, end products of hydrolysis, inhibit cellulases and decrease glucose yields. Aside from these end products, however, other monosa...

  3. Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

    NARCIS (Netherlands)

    Brockow, K.; Garvey, L. H.; Aberer, W.; Atanaskovic-Markovic, M.; Barbaud, A.; Bilo, M. B.; Bircher, A.; Blanca, M.; Bonadonna, B.; Campi, P.; Castro, E.; Cernadas, J. R.; Chiriac, A. M.; Demoly, P.; Grosber, M.; Gooi, J.; Lombardo, C.; Mertes, P. M.; Mosbech, H.; Nasser, S.; Pagani, M.; Ring, J.; Romano, A.; Scherer, K.; Schnyder, B.; Testi, S.; Torres, M.; Trautmann, A.; Terreehorst, I.

    2013-01-01

    Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable

  4. 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

  5. Skin test concentrations for systemically administered drugs -- an ENDA/EAACI Drug Allergy Interest Group position paper

    DEFF Research Database (Denmark)

    Brockow, K; Garvey, L H; Aberer, W

    2013-01-01

    Skin tests are of paramount importance for the evaluation of drug hypersensitivity reactions. Drug skin tests are often not carried out because of lack of concise information on specific test concentrations. The diagnosis of drug allergy is often based on history alone, which is an unreliable...... indicator of true hypersensitivity.To promote and standardize reproducible skin testing with safe and nonirritant drug concentrations in the clinical practice, the European Network and European Academy of Allergy and Clinical Immunology (EAACI) Interest Group on Drug Allergy has performed a literature...... search on skin test drug concentration in MEDLINE and EMBASE, reviewed and evaluated the literature in five languages using the GRADE system for quality of evidence and strength of recommendation. Where the literature is poor, we have taken into consideration the collective experience of the group...

  6. An inert 3D emulsification device for individual precipitation and concentration of amorphous drug nanoparticles.

    Science.gov (United States)

    Lorenz, T; Bojko, S; Bunjes, H; Dietzel, A

    2018-02-13

    Nanosizing increases the specific surface of drug particles, leading to faster dissolution inside the organism and improving the bioavailability of poorly water-soluble drugs. A novel approach for the preparation of drug nanoparticles in water using chemically inert microfluidic emulsification devices is presented in this paper. A lithographic fabrication sequence was established, allowing fabrication of intersecting and coaxial channels of different depths in glass as is required for 3D flow-focusing. Fenofibrate was used as a model for active pharmaceutical ingredients with very low water solubility in the experiments. It was dissolved in ethyl acetate and emulsified in water, as allowed by the 3D flow-focusing geometry. In the thread formation regime, the drug solution turned into monodisperse droplets of sizes down to below 1 μm. Fast supersaturation occurs individually in each droplet, as the disperse phase solvent progressively diffuses into the surrounding water. Liquid antisolvent precipitation results in highly monodisperse and amorphous nanoparticles of sizes down to 128 nm which can be precisely controlled by the continuous and disperse phase pressure. By comparing optically measured droplet sizes with particle sizes by dynamic light scattering, we could confirm that exactly one particle forms in every droplet. Furthermore, a downstream on-chip concentration allowed withdrawal of major volumes of only the continuous phase fluid which enabled an increase of particle concentration by up to 250 times.

  7. High Concentrations of Tranexamic Acid Inhibit Ionotropic Glutamate Receptors.

    Science.gov (United States)

    Lecker, Irene; Wang, Dian-Shi; Kaneshwaran, Kirusanthy; Mazer, C David; Orser, Beverley A

    2017-07-01

    The antifibrinolytic drug tranexamic acid is structurally similar to the amino acid glycine and may cause seizures and myoclonus by acting as a competitive antagonist of glycine receptors. Glycine is an obligatory co-agonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. Thus, it is plausible that tranexamic acid inhibits NMDA receptors by acting as a competitive antagonist at the glycine binding site. The aim of this study was to determine whether tranexamic acid inhibits NMDA receptors, as well as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate subtypes of ionotropic glutamate receptors. Tranexamic acid modulation of NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate receptors was studied using whole cell voltage-clamp recordings of current from cultured mouse hippocampal neurons. Tranexamic acid rapidly and reversibly inhibited NMDA receptors (half maximal inhibitory concentration = 241 ± 45 mM, mean ± SD; 95% CI, 200 to 281; n = 5) and shifted the glycine concentration-response curve for NMDA-evoked current to the right. Tranexamic acid also inhibited α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (half maximal inhibitory concentration = 231 ± 91 mM; 95% CI, 148 to 314; n = 5 to 6) and kainate receptors (half maximal inhibitory concentration = 90 ± 24 mM; 95% CI, 68 to 112; n = 5). Tranexamic acid inhibits NMDA receptors likely by reducing the binding of the co-agonist glycine and also inhibits α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors. Receptor blockade occurs at high millimolar concentrations of tranexamic acid, similar to the concentrations that occur after topical application to peripheral tissues. Glutamate receptors in tissues including bone, heart, and nerves play various physiologic roles, and tranexamic acid inhibition of these receptors may contribute to adverse drug effects.

  8. Diverse microbial species survive high ammonia concentrations

    Science.gov (United States)

    Kelly, Laura C.; Cockell, Charles S.; Summers, Stephen

    2012-04-01

    Planetary protection regulations are in place to control the contamination of planets and moons with terrestrial micro-organisms in order to avoid jeopardizing future scientific investigations relating to the search for life. One environmental chemical factor of relevance in extraterrestrial environments, specifically in the moons of the outer solar system, is ammonia (NH3). Ammonia is known to be highly toxic to micro-organisms and may disrupt proton motive force, interfere with cellular redox reactions or cause an increase of cell pH. To test the survival potential of terrestrial micro-organisms exposed to such cold, ammonia-rich environments, and to judge whether current planetary protection regulations are sufficient, soil samples were exposed to concentrations of NH3 from 5 to 35% (v/v) at -80°C and room temperature for periods up to 11 months. Following exposure to 35% NH3, diverse spore-forming taxa survived, including representatives of the Firmicutes (Bacillus, Sporosarcina, Viridibacillus, Paenibacillus, Staphylococcus and Brevibacillus) and Actinobacteria (Streptomyces). Non-spore forming organisms also survived, including Proteobacteria (Pseudomonas) and Actinobacteria (Arthrobacter) that are known to have environmentally resistant resting states. Clostridium spp. were isolated from the exposed soil under anaerobic culture. High NH3 was shown to cause a reduction in viability of spores over time, but spore morphology was not visibly altered. In addition to its implications for planetary protection, these data show that a large number of bacteria, potentially including spore-forming pathogens, but also environmentally resistant non-spore-formers, can survive high ammonia concentrations.

  9. The Impact of Serum Drug Concentration on the Efficacy of Imipramine, Pregabalin and their Combination in Painful Polyneuropathy

    DEFF Research Database (Denmark)

    Sindrup, Søren Hein; Holbech, Jakob Vormstrup; Bach, Flemming W

    2017-01-01

    OBJECTIVE: The serum concentration-effect relation was explored for first line drugs in neuropathic pain and aimed to determine if efficacy could be increased. METHODS: Data from a randomized, placebo-controlled, cross-over trial on imipramine, pregabalin and their combination in painful...... polyneuropathy were used. Treatment periods were of 4 weeks' duration, outcome was the weekly median of daily pain rated by a 0-10 numeric scale, and drug concentrations were determined by high-performance liquid chromatography. RESULTS: In 47 patients pain was reduced -1.0 (95% CI -1.5:-0.6) by imipramine, -0.......178). There was no correlation between drug concentration and pain reduction for imipramine (r= 0.17, P=0.247), whereas there was a marginally, positive correlation for pregabalin (r=0.28, P=0.057). There was no interaction between treatment and concentration classes (imipramine

  10. Considerations for effect site pharmacokinetics to estimate drug exposure: concentrations of antibiotics in the lung.

    Science.gov (United States)

    Rodvold, Keith A; Hope, William W; Boyd, Sara E

    2017-10-01

    Bronchoalveolar lavage (BAL) and microdialysis have become the most reliable and relevant methods for measuring lung concentrations of antibiotics, with the majority of BAL studies involving either healthy adult subjects or patients undergoing diagnostic bronchoscopy. Emphasis on the amount of drug that reaches the site of infection is increasingly recognized as necessary to determine whether a dose selection will translate to good clinical outcomes in the treatment of patients with pneumonia. Observed concentrations and/or parameters of exposure (e.g. area-under-the-curve) need to be incorporated with pharmacokinetic-pharmacodynamic indices so that rational dose selection can be identified for specific pathogens and types of pneumonic infection (community-acquired vs hospital-acquired bacterial pneumonia, including ventilator-associated bacterial pneumonia). Although having measured plasma or lung concentration-time data from critically ill patients to incorporate into pharmacokinetic-pharmacodynamic models is very unlikely during drug development, it is essential that altered distribution, augmented renal clearance, and renal or hepatic dysfunction should be considered. Notably, the number of published studies involving microdialysis and intrapulmonary penetration of antibiotics has been limited and mainly involve beta-lactam agents, levofloxacin, and fosfomycin. Opportunities to measure in high-resolution effect site spatial pharmacokinetics (e.g. with MALDI-MSI or PET imaging) and in vivo continuous drug concentrations (e.g. with aptamer-based probes) now exist. Going forward these studies could be incorporated into antibiotic development programs for pneumonia in order to further increase the probability of candidate success. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. High-efficiency concentrator silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Sinton, R.A.; Cuevas, A.; King, R.R.; Swanson, R.M. (Stanford Univ., CA (USA). Solid-State Electronics Lab.)

    1990-11-01

    This report presents results from extensive process development in high-efficiency Si solar cells. An advanced design for a 1.56-cm{sup 2} cell with front grids achieved 26% efficiency at 90 suns. This is especially significant since this cell does not require a prismatic cover glass. New designs for simplified backside-contact solar cells were advanced from a status of near-nonfunctionality to demonstrated 21--22% for one-sun cells in sizes up to 37.5 cm{sup 2}. An efficiency of 26% was achieved for similar 0.64-cm{sup 2} concentrator cells at 150 suns. More fundamental work on dopant-diffused regions is also presented here. The recombination vs. various process and physical parameters was studied in detail for boron and phosphorous diffusions. Emitter-design studies based solidly upon these new data indicate the performance vs design parameters for a variety of the cases of most interest to solar cell designers. Extractions of p-type bandgap narrowing and the surface recombination for p- and n-type regions from these studies have a generality that extends beyond solar cells into basic device modeling. 68 refs., 50 figs.

  12. High-flux solar concentration with imaging designs

    Energy Technology Data Exchange (ETDEWEB)

    Feuermann, D. [Ben-Gurion University of the Negev (Israel). Jacob Blaustein Institute for Desert Research; Gordon, J.M. [Ben-Gurion University of the Negev (Israel). Jacob Blaustein Institute for Desert Research; Ben-Gurion University of the Negev (Israel). Dept. of Mechanical Engineering; Ries, H. [Ries and Partners, Munich (Germany)

    1999-02-01

    Most large solar concentrators designed for high flux concentration at high collection efficiency are based on imaging primary mirrors and nonimaging secondary concentrators. In this paper, we offer an alternative purely imaging two-stage solar concentrator that can attain high flux concentration at high collection efficiency. Possible practical virtues include: (1) an inherent large gap between absorber and secondary mirror; (2) a restricted angular range on the absorber; and (3) an upward-facing receiver where collected energy can be extracted via the (shaded) apex of the parabola. We use efficiency-concentration plots to characterize the solar concentrators considered, and to evaluate the potential improvements with secondary concentrators. (author)

  13. Plasma vs heart tissue concentration in humans - literature data analysis of drugs distribution.

    Science.gov (United States)

    Tylutki, Zofia; Polak, Sebastian

    2015-03-12

    Little is known about the uptake of drugs into the human heart, although it is of great importance nowadays, when science desires to predict tissue level behavior rather than to measure it. Although the drug concentration in cardiac tissue seems a better predictor for physiological and electrophysiological changes than its level in plasma, knowledge of this value is very limited. Tissue to plasma partition coefficients (Kp) come to rescue since they characterize the distribution of a drug among tissues as being one of the input parameters in physiologically based pharmacokinetic (PBPK) models. The article reviews cardiac surgery and forensic medical studies to provide a reference for drug concentrations in human cardiac tissue. Firstly, the focus is on whether a drug penetrates into heart tissue at a therapeutic level; the provided values refer to antibiotics, antifungals and anticancer drugs. Drugs that directly affect cardiomyocyte electrophysiology are another group of interest. Measured levels of amiodarone, digoxin, perhexiline and verapamil in different sites in human cardiac tissue where the compounds might meet ion channels, gives an insight into how these more lipophilic drugs penetrate the heart. Much data are derived from postmortem studies and they provide insight to the cardiac distribution of more than 200 drugs. The analysis depicts potential problems in defining the active concentration location, what may indirectly suggest multiple mechanisms involved in the drug distribution within the heart. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  14. Horizontally staggered lightguide solar concentrator with lateral displacement tracking for high concentration applications.

    Science.gov (United States)

    Ma, Hongcai; Wu, Lin

    2015-07-10

    We present the design of a horizontally staggered lightguide solar concentrator with lateral displacement tracking for high concentration applications. This solar concentrator consists of an array of telecentric primary concentrators, a horizontally staggered lightguide layer, and a vertically tapered lightguide layer. The primary concentrator is realized by two plano-aspheric lenses with lateral movement and maintains a high F-number over an angle range of ±23.5°. The results of the simulations show that the solar concentrator achieves a high concentration ratio of 500× with ±0.5° of acceptance angle by a single-axis tracker and dual lateral translation stages.

  15. Cementification for radioactive waste including high-concentration sodium sulfate and high-concentration radioactive nuclide

    International Nuclear Information System (INIS)

    Miyamoto, Shinya; Sato, Tatsuaki; Sasoh, Michitaka; Sakurai, Jiro; Takada, Takao

    2005-01-01

    For the cementification of radioactive waste that has large concentrations of sodium sulfate and radioactive nuclide, a way of fixation for sulfate ion was studied comprising the pH control of water in contact with the cement solid, and the removal of the excess water from the cement matrix to prevent hydrogen gas generation with radiolysis. It was confirmed that the sulfate ion concentration in the contacted water with the cement solid is decreased with the formation of ettringite or barium sulfate before solidification, the pH value of the pore water in the cement solid can control less than 12.5 by the application of zeolite and a low-alkali cement such as alumina cement or fly ash mixed cement, and removal of the excess water from the cement matrix by heating is possible with aggregate addition. Consequently, radioactive waste including high-concentration sodium sulfate and high-concentration radioactive nuclide can be solidified with cementitious materials. (author)

  16. The toxicological significance of post-mortem drug concentrations in bile.

    Science.gov (United States)

    Ferner, Robin E; Aronson, Jeffrey K

    2018-01-01

    Some authors have proposed that post-mortem drug concentrations in bile are useful in estimating concentrations in blood. Both The International Association of Forensic Toxicologists (TIAFT) and the US Federal Aviation Administration recommend that samples of bile should be obtained in some circumstances. Furthermore, standard toxicological texts compare blood and bile concentrations, implying that concentrations in bile are of forensic value. To review the evidence on simultaneous measurements of blood and bile drug concentrations reported in the medical literature. We made a systematic search of EMBASE 1980-2016 using the search terms ("bile/" OR "exp drug bile level/concentration/") AND "drug blood level/concentration/", PubMed 1975-2017 for ("bile[tw]" OR "biliary[tw]") AND ("concentration[tw]" OR "concentrations[tw]" OR "level[tw]" OR "levels[tw]") AND "post-mortem[tw]" and also MEDLINE 1990-2016 for information on drugs whose biliary concentrations were mentioned in standard textbooks. The search was limited to human studies without language restrictions. We also examined recent reviews, indexes of relevant journals and citations in Web of Science and Google Scholar. We calculated the bile:blood concentration ratio. The searches together yielded 1031 titles with abstracts. We scanned titles and abstracts for relevance and retrieved 230, of which 161 were considered further. We excluded 49 papers because: the paper reported only one case (30 references); the data referred only to a metabolite (1); the work was published before 1980 (3); the information concerned only samples taken during life (10); or the paper referred to a toxin or unusual recreational drug (5). The remaining 112 papers provided data for analysis, with at least two observations for each of 58 drugs. Bile:blood concentration ratios: Median bile:blood concentration ratios varied from 0.18 (range 0.058-0.32) for dextromoramide to 520 (range 0.62-43,000) for buprenorphine. Median bile

  17. Drug Concentration Thresholds Predictive of Therapy Failure and Death in Children With Tuberculosis: Bread Crumb Trails in Random Forests.

    Science.gov (United States)

    Swaminathan, Soumya; Pasipanodya, Jotam G; Ramachandran, Geetha; Hemanth Kumar, A K; Srivastava, Shashikant; Deshpande, Devyani; Nuermberger, Eric; Gumbo, Tawanda

    2016-11-01

     The role of drug concentrations in clinical outcomes in children with tuberculosis is unclear. Target concentrations for dose optimization are unknown.  Plasma drug concentrations measured in Indian children with tuberculosis were modeled using compartmental pharmacokinetic analyses. The children were followed until end of therapy to ascertain therapy failure or death. An ensemble of artificial intelligence algorithms, including random forests, was used to identify predictors of clinical outcome from among 30 clinical, laboratory, and pharmacokinetic variables.  Among the 143 children with known outcomes, there was high between-child variability of isoniazid, rifampin, and pyrazinamide concentrations: 110 (77%) completed therapy, 24 (17%) failed therapy, and 9 (6%) died. The main predictors of therapy failure or death were a pyrazinamide peak concentration <38.10 mg/L and rifampin peak concentration <3.01 mg/L. The relative risk of these poor outcomes below these peak concentration thresholds was 3.64 (95% confidence interval [CI], 2.28-5.83). Isoniazid had concentration-dependent antagonism with rifampin and pyrazinamide, with an adjusted odds ratio for therapy failure of 3.00 (95% CI, 2.08-4.33) in antagonism concentration range. In regard to death alone as an outcome, the same drug concentrations, plus z scores (indicators of malnutrition), and age <3 years, were highly ranked predictors. In children <3 years old, isoniazid 0- to 24-hour area under the concentration-time curve <11.95 mg/L × hour and/or rifampin peak <3.10 mg/L were the best predictors of therapy failure, with relative risk of 3.43 (95% CI, .99-11.82).  We have identified new antibiotic target concentrations, which are potential biomarkers associated with treatment failure and death in children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  18. The frequency of drugs among Danish drivers before and after the introduction of fixed concentration limits

    DEFF Research Database (Denmark)

    Steentoft, Anni; Simonsen, Kirsten Wiese; Linnet, Kristian

    2010-01-01

    Until July 2007, the driving under the influence of drugs (DUID) legislation in Denmark was based on impairment, evaluated on the basis of a clinical investigation and toxicological analyses, but in 2007 fixed concentration limits were introduced into the Danish traffic legislation. The objective...... for this study was to investigate the prevalence of medication and illicit drugs among Danish drivers before and after 2007.......Until July 2007, the driving under the influence of drugs (DUID) legislation in Denmark was based on impairment, evaluated on the basis of a clinical investigation and toxicological analyses, but in 2007 fixed concentration limits were introduced into the Danish traffic legislation. The objective...

  19. Risk factors associated with high linezolid trough plasma concentrations.

    Science.gov (United States)

    Morata, L; De la Calle, C; Gómez-Cerquera, J M; Manzanedo, L; Casals, G; Brunet, M; Cobos-Trigueros, N; Martínez, J A; Mensa, J; Soriano, A

    2016-06-01

    The major concern of linezolid is the adverse events. High linezolid trough serum concentration (Cmin) has been associated with toxicity. The aim of this study was to analyze factors associated with high Cmin. Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High Cmin was considered when it was >8 mg/L. Univariate and multivariate analysis were performed. 34.6% patients had a Cmin >8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD 8 was the renal function. Patients with an eGF 80 mL/min (OR: 4.273) and there was a trend towards a high Cmin in patients with eGF between 40-80 mL/min (OR: 2.109). High Cmin were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.

  20. Can fluconazole concentrations in saliva be used for therapeutic drug monitoring?

    NARCIS (Netherlands)

    Koks, C. H.; Crommentuyn, K. M.; Hoetelmans, R. M.; Mathôt, R. A.; Beijnen, J. H.

    2001-01-01

    The saliva/plasma concentration ratio of fluconazole was investigated in 22 HIV-1-infected individuals with an oropharyngeal Candida infection to determine whether saliva fluconazole concentrations could provide useful information for therapeutic drug monitoring in this population. Steady-state

  1. Clinical significance of 2 h plasma concentrations of first-line anti-tuberculosis drugs

    DEFF Research Database (Denmark)

    Prahl, Julie B; Johansen, Isik S; Cohen, Arieh S

    2014-01-01

    OBJECTIVES: To study 2 h plasma concentrations of the first-line tuberculosis drugs isoniazid, rifampicin, ethambutol and pyrazinamide in a cohort of patients with tuberculosis in Denmark and to determine the relationship between the concentrations and the clinical outcome. METHODS: After 6......-207 days of treatment (median 34 days) 2 h blood samples were collected from 32 patients with active tuberculosis and from three patients receiving prophylactic treatment. Plasma concentrations were determined using LC-MS/MS. Normal ranges were obtained from the literature. Clinical charts were reviewed...... failure occurred more frequently when the concentrations of isoniazid and rifampicin were both below the normal ranges (P = 0.013) and even more frequently when they were below the median 2 h drug concentrations obtained in the study (P = 0.005). CONCLUSIONS: At 2 h, plasma concentrations of isoniazid...

  2. Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

    Directory of Open Access Journals (Sweden)

    Hiroaki Todo

    2013-12-01

    Full Text Available Skin permeation experiments have been broadly done since 1970s to 1980s as an evaluation method for transdermal drug delivery systems. In topically applied drug and cosmetic formulations, skin concentration of chemical compounds is more important than their skin permeations, because primary target site of the chemical compounds is skin surface or skin tissues. Furthermore, the direct pharmacological reaction of a metabolically stable drug that binds with specific receptors of known expression levels in an organ can be determined by Hill’s equation. Nevertheless, little investigation was carried out on the test method of skin concentration after topically application of chemical compounds. Recently we investigated an estimating method of skin concentration of the chemical compounds from their skin permeation profiles. In the study, we took care of “3Rs” issues for animal experiments. We have proposed an equation which was capable to estimate animal skin concentration from permeation profile through the artificial membrane (silicone membrane and animal skin. This new approach may allow the skin concentration of a drug to be predicted using Fick’s second law of diffusion. The silicone membrane was found to be useful as an alternative membrane to animal skin for predicting skin concentration of chemical compounds, because an extremely excellent extrapolation to animal skin concentration was attained by calculation using the silicone membrane permeation data. In this chapter, we aimed to establish an accurate and convenient method for predicting the concentration profiles of drugs in the skin based on the skin permeation parameters of topically active drugs derived from steady-state skin permeation experiments.

  3. Cure of tuberculosis despite serum concentrations of antituberculosis drugs below published reference ranges.

    Science.gov (United States)

    Meloni, Monica; Corti, Natascia; Müller, Daniel; Henning, Lars; Gutteck, Ursula; von Braun, Amrei; Weber, Rainer; Fehr, Jan

    2015-01-01

    Therapeutic target serum concentrations of first-line antituberculosis drugs have not been well defined in clinical studies in tuberculosis (TB) patients. We retrospectively investigated the estimated maximum serum concentrations (eC max) of antituberculosis drugs and clinical outcome of TB patients with therapeutic drug monitoring performed between 2010-2012 at our institution, and follow-up until March 2014. The eC max was defined as the highest serum concentration during a sampling period (2, 4 and 6 hours after drug ingestion). We compared the results with published eC max values, and categorised them as either "within reference range", "low eC max", or "very low eC max".Low/very low eC max-levels were defined as follows: isoniazid 2-3/max levels were classified as "low" or "very low". The eC max was below the relevant reference range in 80% of isoniazid, 95% of rifampicin, 30% of pyrazinamide, and 30% of ethambutol measurements. All but one patient were cured of tuberculosis. Although many antituberculosis drug serum concentrations were below the widely used reference ranges, 16 of 17 patients were cured of tuberculosis. These results challenge the use of the published reference ranges for therapeutic drug monitoring.

  4. Hypnosis control based on the minimum concentration of anesthetic drug for maintaining appropriate hypnosis.

    Science.gov (United States)

    Furutani, Eiko; Nishigaki, Yuki; Kanda, Chiaki; Takeda, Toshihiro; Shirakami, Gotaro

    2013-01-01

    This paper proposes a novel hypnosis control method using Auditory Evoked Potential Index (aepEX) as a hypnosis index. In order to avoid side effects of an anesthetic drug, it is desirable to reduce the amount of an anesthetic drug during surgery. For this purpose many studies of hypnosis control systems have been done. Most of them use Bispectral Index (BIS), another hypnosis index, but it has problems of dependence on anesthetic drugs and nonsmooth change near some particular values. On the other hand, aepEX has an ability of clear distinction between patient consciousness and unconsciousness and independence of anesthetic drugs. The control method proposed in this paper consists of two elements: estimating the minimum effect-site concentration for maintaining appropriate hypnosis and adjusting infusion rate of an anesthetic drug, propofol, using model predictive control. The minimum effect-site concentration is estimated utilizing the property of aepEX pharmacodynamics. The infusion rate of propofol is adjusted so that effect-site concentration of propofol may be kept near and always above the minimum effect-site concentration. Simulation results of hypnosis control using the proposed method show that the minimum concentration can be estimated appropriately and that the proposed control method can maintain hypnosis adequately and reduce the total infusion amount of propofol.

  5. Prevalence of alcohol and other drugs and the concentrations in blood of drivers killed in road traffic crashes in Sweden.

    Science.gov (United States)

    Ahlner, Johan; Holmgren, Anita; Jones, Alan Wayne

    2014-03-01

    Drunk or drug-impaired drivers represent a major public health and societal problem worldwide. Because over 95% of drivers killed on the roads in Sweden are autopsied, reliable information is available about the use of alcohol and/or other drug before the crash. This retrospective 4-year study (2008-2011) used a forensic toxicology database (TOXBASE) to evaluate the concentrations of alcohol and other drugs in blood samples from drivers killed in road-traffic crashes. The mean age of all victims (N = 895) was 48 ± 20 years, and the majority were male (86%). In 504 drivers (56%), the results of toxicological analysis were negative and these victims were older; mean age (± SD) 47 ± 20 years, than alcohol positive cases (35 ± 14 years) and illicit drug users (34 ± 15 years). In 21% of fatalities, blood-alcohol concentration (BAC) was above the statutory limit for driving (0.2 g/L), although the median BAC was appreciably higher (1.72 g/L). Illicit drugs (mainly amphetamine and cannabis) were identified in ~7% of victims, either alone (2.5%), together with alcohol (1.8%) or a prescription drug (2%). The psychoactive prescription drugs identified were mainly benzodiazepines, z-hypnotics and tramadol, which were found in the blood of 7.6% of crash victims. The high median BAC in fatally-injured drivers speaks strongly towards alcohol-induced impairment as being responsible for the crash. Compared with alcohol, the prevalence of illicit and psychoactive prescription drugs was fairly low despite a dramatic increase in the number of drug-impaired drivers arrested by the police after a zero-tolerance law was introduced in 1999.

  6. Plasma Drug Concentrations of Orally Administered Rosuvastatin in Hispaniolan Amazon Parrots (Amazona ventralis).

    Science.gov (United States)

    Beaufrère, Hugues; Papich, Mark G; Brandão, João; Nevarez, Javier; Tully, Thomas N

    2015-03-01

    Atherosclerotic diseases are common in pet psittacine birds, in particular Amazon parrots. While hypercholesterolemia and dyslipidemia have not definitely been associated with increased susceptibility to atherosclerosis in parrots, these are important and well-known risk factors in humans. Therefore statin drugs such as rosuvastatin constitute the mainstay of human treatment of dyslipidemia and the prevention of atherosclerosis. No pharmacologic studies have been performed in psittacine birds despite the high prevalence of atherosclerosis in captivity. Thirteen Hispaniolan Amazon parrots were used to test a single oral dose of 10 mg/kg of rosuvastatin with blood sampling performed according to a balanced incomplete block design over 36 hours. Because low plasma concentrations were produced in the first study, a subsequent pilot study using a dose of 25 mg/kg in 2 Amazon parrots was performed. Most plasma samples for the 10 mg/kg dose and all samples for the 25 mg/kg dose had rosuvastatin concentration below the limits of quantitation. For the 10 mg/kg study, the median peak plasma concentration and time to peak plasma concentration were 0.032 μg/mL and 2 hours, respectively. Our results indicate that rosuvastatin does not appear suitable in Amazon parrots as compounded and used at the dose in this study. Pharmacodynamic studies investigating lipid-lowering effects of statins rather than pharmacokinetic studies may be more practical and cost effective in future studies to screen for a statin with more ideal properties for potential use in psittacine dyslipidemia and atherosclerotic diseases.

  7. Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin

    Science.gov (United States)

    Foster, Derek M.; Martin, Luke G.; Papich, Mark G.

    2016-01-01

    Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC90 for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900

  8. Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin, Florfenicol, Ceftiofur, or Tulathromycin.

    Directory of Open Access Journals (Sweden)

    Derek M Foster

    Full Text Available Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined exceeded the MIC90 of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL, and the MIC90 for Mannheimia haemolytica (1.0 μg/mL for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations

  9. Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis

    Science.gov (United States)

    Heinrichs, M. Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D.; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A.; Blumberg, Henry M.; Vashakidze, Sergo

    2017-01-01

    ABSTRACT Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary (n = 6 patients), mass-like (n = 3 patients), or consolidative (n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis (R = −0.66, P = 0.04) and acid-fast bacilli (R = −0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. PMID:28373198

  10. Lung Tissue Concentrations of Pyrazinamide among Patients with Drug-Resistant Pulmonary Tuberculosis.

    Science.gov (United States)

    Kempker, Russell R; Heinrichs, M Tobias; Nikolaishvili, Ketino; Sabulua, Irina; Bablishvili, Nino; Gogishvili, Shota; Avaliani, Zaza; Tukvadze, Nestani; Little, Brent; Bernheim, Adam; Read, Timothy D; Guarner, Jeannette; Derendorf, Hartmut; Peloquin, Charles A; Blumberg, Henry M; Vashakidze, Sergo

    2017-06-01

    Improved knowledge regarding the tissue penetration of antituberculosis drugs may help optimize drug management. Patients with drug-resistant pulmonary tuberculosis undergoing adjunctive surgery were enrolled. Serial serum samples were collected, and microdialysis was performed using ex vivo lung tissue to measure pyrazinamide concentrations. Among 10 patients, the median pyrazinamide dose was 24.7 mg/kg of body weight. Imaging revealed predominant lung lesions as cavitary ( n = 6 patients), mass-like ( n = 3 patients), or consolidative ( n = 1 patient). On histopathology examination, all tissue samples had necrosis; eight had a pH of ≤5.5. Tissue samples from two patients were positive for Mycobacterium tuberculosis by culture (pH 5.5 and 7.2). All 10 patients had maximal serum pyrazinamide concentrations within the recommended range of 20 to 60 μg/ml. The median lung tissue free pyrazinamide concentration was 20.96 μg/ml. The median tissue-to-serum pyrazinamide concentration ratio was 0.77 (range, 0.54 to 0.93). There was a significant inverse correlation between tissue pyrazinamide concentrations and the amounts of necrosis ( R = -0.66, P = 0.04) and acid-fast bacilli ( R = -0.75, P = 0.01) identified by histopathology. We found good penetration of pyrazinamide into lung tissue among patients with pulmonary tuberculosis with a variety of radiological lesion types. Our tissue pH results revealed that most lesions had a pH conducive to pyrazinamide activity. The tissue penetration of pyrazinamide highlights its importance in both drug-susceptible and drug-resistant antituberculosis treatment regimens. Copyright © 2017 American Society for Microbiology.

  11. 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

  12. Flexing the PECs: Predicting environmental concentrations of veterinary drugs in Canadian agricultural soils.

    Science.gov (United States)

    Kullik, Sigrun A; Belknap, Andrew M

    2017-03-01

    Veterinary drugs administered to food animals primarily enter ecosystems through the application of livestock waste to agricultural land. Although veterinary drugs are essential for protecting animal health, their entry into the environment may pose a risk for nontarget organisms. A means to predict environmental concentrations of new veterinary drug ingredients in soil is required to assess their environmental fate, distribution, and potential effects. The Canadian predicted environmental concentrations in soil (PECsoil) for new veterinary drug ingredients for use in intensively reared animals is based on the approach currently used by the European Medicines Agency for VICH Phase I environmental assessments. The calculation for the European Medicines Agency PECsoil can be adapted to account for regional animal husbandry and land use practices. Canadian agricultural practices for intensively reared cattle, pigs, and poultry differ substantially from those in the European Union. The development of PECsoil default values and livestock categories representative of typical Canadian animal production methods and nutrient management practices culminates several years of research and an extensive survey and analysis of the scientific literature, Canadian agricultural statistics, national and provincial management recommendations, veterinary product databases, and producers. A PECsoil can be used to rapidly identify new veterinary drugs intended for intensive livestock production that should undergo targeted ecotoxicity and fate testing. The Canadian PECsoil model is readily available, transparent, and requires minimal inputs to generate a screening level environmental assessment for veterinary drugs that can be refined if additional data are available. PECsoil values for a hypothetical veterinary drug dosage regimen are presented and discussed in an international context. Integr Environ Assess Manag 2017;13:331-341. © 2016 Her Majesty the Queen in Right of Canada

  13. Multijunction Photovoltaic Technologies for High-Performance Concentrators: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    McConnell, R.; Symko-Davies, M.

    2006-05-01

    Multijunction solar cells provide high-performance technology pathways leading to potentially low-cost electricity generated from concentrated sunlight. The National Center for Photovoltaics at the National Renewable Energy Laboratory has funded different III-V multijunction solar cell technologies and various solar concentration approaches. Within this group of projects, III-V solar cell efficiencies of 41% are close at hand and will likely be reported in these conference proceedings. Companies with well-developed solar concentrator structures foresee installed system costs of $3/watt--half of today's costs--within the next 2 to 5 years as these high-efficiency photovoltaic technologies are incorporated into their concentrator photovoltaic systems. These technology improvements are timely as new large-scale multi-megawatt markets, appropriate for high performance PV concentrators, open around the world.

  14. [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.

  15. Applications of nonimaging optics for very high solar concentrations

    International Nuclear Information System (INIS)

    O'Gallagher, J.; Winston, R.

    1997-01-01

    Using the principles and techniques of nonimaging optics, solar concentrations that approach the theoretical maximum can be achieved. This has applications in solar energy collection wherever concentration is desired. In this paper, we survey recent progress in attaining and using high and ultrahigh solar fluxes. We review a number of potential applications for highly concentrated solar energy and the current status of the associated technology. By making possible new and unique applications for intense solar flux, these techniques have opened a whole new frontier for research and development of potentially economic uses of solar energy

  16. Case study of elevated layers of high sulfate concentration

    International Nuclear Information System (INIS)

    McNaughton, D.J.; Orgill, M.M.

    1979-01-01

    During studies in August 1976 that were part of the Multi-State Atmospheric Power Production Pollutant Study (MAP3S), Alkezweeny et al., (1977) noted that in the Milwaukee urban plume, layers of relatively high sulfate concentrations occurred at high altitudes with respect to the boundary layer. This paper represents a progress report on studies undertaken to investigate possible causes for a bimodel vertical profile of sulfate concentrations. Data presented by Alkezweeny et al., (1977) serve as a basis for this study. Data from August 23, 1976, and August 24, 1978, indicate concentrations relatively high in sulfate, at 1000 and 6000 ft, respectively, with lower concentrations at lower altitudes. Concentrations of trace metals also indicate no peaks in the vertical concentration profiles above the surface. Initial studies of the high, elevated sulfate concentrations have centered on the August 23 measurements taken over southeast Wisconsin using synoptic data from the national weather service, emissions data from the national emissions data bank system (EPA), air quality data from the national air surveillance network (EPA), and satellite photographs from the EROS Data Center

  17. High mobility and high concentration Type-III heterojunction FET

    Science.gov (United States)

    Tsu, R.; Fiddy, M. A.; Her, T.

    2018-02-01

    The PN junction was introduced in transistors by doping, resulting in high losses due to Coulomb scattering from the dopants. The MOSFET introduced carriers in the form of electrons and holes with an applied bias to the oxide barrier, resulting in carrier transfer without doping. This avoids high scattering losses and dominates the IC industries. With heterojunctions having valence-band maxima near and even above the conduction-band minimum in the formation of Type-III superlattices, very useful devices, introduced by Tsu, Sai-Halacz, and Esaki, soon followed. If the layer thicknesses are more than the carrier mean-free-path, incoherent scattering results in the formation of carrier transfer via diffusion instead of opening up new energy gaps. The exploitation of carriers without scattering represents a new and significant opportunity in what we call a Broken Gap Heterojunction FET.

  18. Differences in Swallowing between High and Low Concentration Taste Stimuli

    Directory of Open Access Journals (Sweden)

    Ahmed Nagy

    2014-01-01

    Full Text Available Taste is a property that is thought to potentially modulate swallowing behavior. Whether such effects depend on taste, intensity remains unclear. This study explored differences in the amplitudes of tongue-palate pressures in swallowing as a function of taste stimulus concentration. Tongue-palate pressures were collected in 80 healthy women, in two age groups (under 40, over 60, stratified by genetic taste status (nontasters, supertasters. Liquids with different taste qualities (sweet, sour, salty, and bitter were presented in high and low concentrations. General labeled magnitude scale ratings captured perceived taste intensity and liking/disliking of the test liquids. Path analysis explored whether factors of taste, concentration, age group, and/or genetic taste status impacted: (1 perceived intensity; (2 palatability; and (3 swallowing pressures. Higher ratings of perceived intensity were found in supertasters and with higher concentrations, which were more liked/disliked than lower concentrations. Sweet stimuli were more palatable than sour, salty, or bitter stimuli. Higher concentrations elicited stronger tongue-palate pressures independently and in association with intensity ratings. The perceived intensity of a taste stimulus varies as a function of stimulus concentration, taste quality, participant age, and genetic taste status and influences swallowing pressure amplitudes. High-concentration salty and sour stimuli elicit the greatest tongue-palate pressures.

  19. Impact of concentration and rate of intraluminal drug delivery on absorption and gut wall metabolism of verapamil in humans.

    Science.gov (United States)

    Glaeser, Hartmut; Drescher, Siegfried; Hofmann, Ute; Heinkele, Georg; Somogyi, Andrew A; Eichelbaum, Michel; Fromm, Martin F

    2004-09-01

    In humans gut wall metabolism can be quantitatively as important as hepatic drug metabolism in limiting the systemic exposure to drugs after oral administration. However, it has been proposed that the role of gut wall metabolism might be overemphasized, because high luminal drug concentrations would lead to a saturation of gut wall metabolism. Therefore we investigated the impact of concentration and rate of intraluminal drug delivery on absorption (F(abs)) and gastrointestinal extraction (E(GI)) of a luminally administered cytochrome P450 (CYP) 3A4 substrate (verapamil) using a multilumen perfusion catheter in combination with a stable isotope technique. Two 20-cm-long, adjacent jejunal segments were isolated with the multilumen perfusion catheter in 7 subjects. In this study 80 mg of unlabeled verapamil (d0-verapamil 15 min) was infused into one segment over a 15-minute period, 80 mg of 3-fold deuterated verapamil (d3-verapamil 240 min) was administered over a 240-minute period into the other segment, and simultaneously, 5 mg of 7-fold deuterated verapamil (d7-verapamil) was injected intravenously over a 15-minute period. The rate of intraluminal drug delivery had only a modest effect on bioavailability of the verapamil isotopes (after correction for F abs ) (F/F abs d3-verapamil 240 min versus d0-verapamil 15 min, 0.24 +/- 0.10 versus 0.20 +/- 0.09; P d3-verapamil 240 min was 0.50 +/- 0.18 compared with 0.59 +/- 0.14 for d0 -verapamil 15 min ( P d0-verapamil 15 min ) correlated strongly with E GI (d3-verapamil 240 min ) (r = 0.94, P d0-verapamil 15 min /d3-verapamil 240 min (r = 0.62, P =.03). Substantial gut wall metabolism of verapamil occurs in humans and can be predicted from ex vivo data by use of shed enterocytes. The different intraluminal concentrations and rates of intraluminal drug delivery did not lead to a pronounced saturation of intestinal drug metabolism.

  20. Concentration of High Level Radioactive Liquid Waste. Basic data acquisition

    Energy Technology Data Exchange (ETDEWEB)

    Juvenelle, A.; Masson, M.; Garrido, M.H. [DEN/VRH/DRCP/SCPS/LPCP, BP 17171 - 30207 Bagnols sur Ceze Cedex (France)

    2008-07-01

    Full text of publication follows: In order to enhance its knowledge about the concentration of high level liquid waste (HLLW) from the nuclear fuel reprocessing process, a program of studies was defined by Cea. In a large field of acidity, it proposes to characterize the concentrated solution and the obtained precipitates versus the concentration factor. Four steps are considered: quantification of the salting-out effect on the concentrate acidity, acquisition of solubility data, precipitates characterisation versus the concentration factor through aging tests and concentration experimentation starting from simulated fission products solutions. The first results, reported here, connect the acidity of the concentrated solution to the concentration factor and allow us to precise the field of acidity (4 to 12 N) for the next experiments. In this field, solubility data of various elements (Ba, Sr, Zr...) are separately measured at room temperature, in nitric acid in a first time, then in the presence of various species present in medium (TBP, PO{sub 4}{sup 3-}). The reactions between these various elements are then investigated (formation of insoluble mixed compounds) by following the concentration cations in solution and characterising the precipitates. (authors)

  1. Extremely high concentration of folates in premature newborns.

    Science.gov (United States)

    Zikavska, T; Brucknerova, I

    2014-01-01

    Extremely high concentration of folates in premature newborns: case reports. Folates are a group of water soluble compounds, which are important for metabolic processes in human body. These are important during periods of rapid cell growth. The most accurate indicator of long-term folate level status in the body is the determination of red blood cell (RBC) folate concentrations. The optimal level of RBC folate is not known in neonatal period. Authors discuss the reasons for extremely high level of RBC folate concentrations. In our work we present the cases of two premature newborns with extremely high level of RBC folate concentrations, which were analyzed immunochemically on the first day of life and after six weeks of life. In both cases we measured RBC folate concentrations on the 1st day of life. After 6 weeks we found extremely high RBC folate concentration level (5516.67 ng/ml) in the first case after RBC transfusions. In second case after two months of life the RBC folate concentration level was doubled (2335.1 ng/ml) until 24 hours after RBC transfusion compared to levels after birth. The normal range of RBC folate values vary in newborns. The upper limit of daily dose of folic acid in pregnancy and neonatal period is not known. On the other hand it is an easily excreted water-soluble vitamin but in premature newborn it can lead to the disruption of metabolic balance and slow its degradation. Some factors can have an impact on RBC folate concentration. Blood transfusion can be one of the main influences on RBC folate concentration. To clarify these mechanisms further studies are required (Ref. 29).

  2. Influence of drugs of abuse and alcohol upon patients admitted to acute psychiatric wards: physician's assessment compared to blood drug concentrations.

    Science.gov (United States)

    Mordal, Jon; Medhus, Sigrid; Holm, Bjørn; Mørland, Jørg; Bramness, Jørgen G

    2013-06-01

    In acute psychiatric services, rapid and accurate detection of psychoactive substance intake may be required for appropriate diagnosis and intervention. The aim of this study was to investigate the relationship between (a) drug influence as assessed by physicians and (b) blood drug concentrations among patients admitted to acute psychiatric wards. We also explored the possible effects of age, sex, and psychotic symptoms on physician's assessment of drug influence. In a cross-sectional study, the sample comprised 271 consecutive admissions from 2 acute psychiatric wards. At admission, the physician on call performed an overall judgment of drug influence. Psychotic symptoms were assessed with the positive subscale of the Positive and Negative Syndrome Scale. Blood samples were screened for a wide range of psychoactive substances, and quantitative results were used to calculate blood drug concentration scores. Patients were judged as being under the influence of drugs and/or alcohol in 28% of the 271 admissions. Psychoactive substances were detected in 56% of the blood samples. Altogether, 15 different substances were found; up to 8 substances were found in samples from 1 patient. Markedly elevated blood drug concentration scores were estimated for 15% of the patients. Physician's assessment was positively related to the blood drug concentration scores (r = 0.52; P < 0.001), to symptoms of excitement, and to the detection of alcohol, cannabis, and amphetamines. The study demonstrates the major impact of alcohol and drugs in acute psychiatric settings and illustrates the challenging nature of the initial clinical assessment.

  3. A compact spectrum splitting concentrator for high concentration photovoltaics based on the dispersion of a lens

    Science.gov (United States)

    He, J.; Flowers, C. A.; Yao, Y.; Atwater, H. A.; Rockett, A. A.; Nuzzo, R. G.

    2018-06-01

    Photovoltaic devices used in conjunction with functional optical elements for light concentration and spectrum splitting are known to be a viable approach for highly efficient photovoltaics. Conventional designs employ discrete optical elements, each with the task of either performing optical concentration or separating the solar spectrum. In the present work, we examine the performance of a compact photovoltaic architecture in which a single lens plays a dual role as both a concentrator and a spectrum splitter, the latter made possible by exploiting its intrinsic dispersion. A four-terminal two-junction InGaP/GaAs device is prepared to validate the concept and illustrates pathways for improvements. A spectral separation in the visible range is demonstrated at the focal point of a plano-convex lens with a geometric concentration ratio of 1104X with respect to the InGaP subcell.

  4. 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...

  5. 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.

  6. Multiphysics modelling and experimental validation of high concentration photovoltaic modules

    International Nuclear Information System (INIS)

    Theristis, Marios; Fernández, Eduardo F.; Sumner, Mike; O'Donovan, Tadhg S.

    2017-01-01

    Highlights: • A multiphysics modelling approach for concentrating photovoltaics was developed. • An experimental campaign was conducted to validate the models. • The experimental results were in good agreement with the models. • The multiphysics modelling allows the concentrator’s optimisation. - Abstract: High concentration photovoltaics, equipped with high efficiency multijunction solar cells, have great potential in achieving cost-effective and clean electricity generation at utility scale. Such systems are more complex compared to conventional photovoltaics because of the multiphysics effect that is present. Modelling the power output of such systems is therefore crucial for their further market penetration. Following this line, a multiphysics modelling procedure for high concentration photovoltaics is presented in this work. It combines an open source spectral model, a single diode electrical model and a three-dimensional finite element thermal model. In order to validate the models and the multiphysics modelling procedure against actual data, an outdoor experimental campaign was conducted in Albuquerque, New Mexico using a high concentration photovoltaic monomodule that is thoroughly described in terms of its geometry and materials. The experimental results were in good agreement (within 2.7%) with the predicted maximum power point. This multiphysics approach is relatively more complex when compared to empirical models, but besides the overall performance prediction it can also provide better understanding of the physics involved in the conversion of solar irradiance into electricity. It can therefore be used for the design and optimisation of high concentration photovoltaic modules.

  7. Determination of safety margins for whole blood concentrations of alcohol and nineteen drugs in driving under the influence cases.

    Science.gov (United States)

    Kristoffersen, Lena; Strand, Dag Helge; Liane, Veronica Horpestad; Vindenes, Vigdis; Tvete, Ingunn Fride; Aldrin, Magne

    2016-02-01

    Legislative limits for driving under the influence of 20 non-alcohol drugs were introduced in Norway in February 2012. Per se limits corresponding to blood alcohol concentrations (BAC) of 0.2g/kg were established for 20 psychoactive drugs, and limits for graded sanctions corresponding to BACs of 0.5 and 1.2g/kg were determined for 13 of these drugs. This new legislation made it possible for the courts to make sentences based on the analytical results, similar to the situation for alcohol. To ensure that the reported concentration is as least as high as the true concentration, with a 99% safety level, safety margins had to be calculated for each of the substances. Diazepam, tetrahydrocannabinol (THC) and alcohol were used as model substances to establish a new model for estimating the safety margins. The model was compared with a previous used model established several years ago, by a similar yet much simpler model, and they were found to be in agreement. The measurement uncertainties depend on the standard batch used, the work list and the measurements' replicate. A Bayesian modelling approach was used to determine the parameters in the model, using a dataset of 4700 diazepam positive specimens and 5400 THC positive specimens. Different safety margins were considered for low and high concentration levels of diazepam (≤2μM (0.6mg/L) and >2μM) and THC (≤0.01μM (0.003mg/L) and >0.01μM). The safety margins were for diazepam 19.5% (≤2μM) and 34% (>2μM), for THC 19.5% (≤0.01μM) and 24.9% (>0.01μM). Concentration dependent safety margins for BAC were based on a dataset of 29500 alcohol positive specimens, and were in the range 10.4% (0.1g/kg) to 4.0% (4.0g/kg) at a 99% safety level. A simplified approach was used to establish safety margins for the compounds amphetamine, MDMA, methamphetamine, alprazolam, phenazepam, flunitrazepam, clonazepam, nitrazepam, oxazepam, buprenorphine, GHB, methadone, ketamine, cocaine, morphine, zolpidem and zopiclone. The

  8. 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.

  9. Vitamin E concentrations in adults with HIV/AIDS on highly active antiretroviral therapy.

    Science.gov (United States)

    Itinoseki Kaio, Daniella J Itinoseki; Rondó, Patricia Helen C; Luzia, Liania Alves; Souza, José Maria P; Firmino, Aline Vale; Santos, Sigrid Sousa

    2014-09-15

    HIV/AIDS patients are probably more predisposed to vitamin E deficiency, considering that they are more exposed to oxidative stress. Additionally, there are an extensive number of drugs in the highly active antiretroviral therapy (HAART) regimens that may interfere with vitamin E concentrations. The objective of this study was to compare serum concentrations of alpha-tocopherol in 182 HIV/AIDS patients receiving different HAART regimens. The patients were divided into three groups according to regimen: nucleoside analog reverse-transcriptase inhibitors (NRTIs) + non-nucleoside analog reverse-transcriptase inhibitors (NNRTIs); NRTIs + protease inhibitors + ritonavir; NRTIs + other classes. Alpha-tocopherol was assessed by high-performance liquid chromatography. Multiple linear regression analysis was used to evaluate the effects of HAART regimen, time of use, and compliance with the regimen on alpha-tocopherol concentrations. Alpha-tocopherol concentrations were on average 4.12 μmol/L lower for the NRTIs + other classes regimen when compared to the NRTIs + NNRTIs regimen (p = 0.037). A positive association (p < 0.001) was observed between alpha-tocopherol and cholesterol concentrations, a finding due, in part, to the relationship between liposoluble vitamins and lipid profile. This study demonstrated differences in alpha-tocopherol concentrations between patients using different HAART regimens, especially regimens involving the use of new drugs. Long-term prospective cohort studies are needed to monitor vitamin E status in HIV/AIDS patients since the beginning of treatment.

  10. Evaluation of radionuclide concentrations in high-level radioactive wastes

    International Nuclear Information System (INIS)

    Fehringer, D.J.

    1985-10-01

    This report describes a possible approach for development of a numerical definition of the term ''high-level radioactive waste.'' Five wastes are identified which are recognized as being high-level wastes under current, non-numerical definitions. The constituents of these wastes are examined and the most hazardous component radionuclides are identified. This report suggests that other wastes with similar concentrations of these radionuclides could also be defined as high-level wastes. 15 refs., 9 figs., 4 tabs

  11. 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.

  12. High indoor radon concentrations in some Swedish waterworks

    International Nuclear Information System (INIS)

    Aakerblom, G.; Hagberg, N.; Mjoenes, L.; Heiberg, A.

    2002-01-01

    High indoor radon concentrations in buildings used for water treatment are not uncommon. When raw water is processed in an open system radon escapes from the water to the indoor air of the premises. It is not unusual that the staff of the waterworks have their offices in the building where the water is processed. If large volumes of water are processed and the evaporated radon can reach the workplaces the indoor radon concentration can be very high even if the radon concentration of the raw water is moderate. Groundwaters from aquifers in bedrock and soil and surface water that has been infiltrated through deposits of sand or gravel have the potential to cause high indoor radon levels. In surface water emanating directly from a lake or a river the radon concentrations are normally too low to cause problems. Three waterworks in central Sweden have been studied, Ludvika, Fredriksberg and Kolbaeck. The radon concentrations in the raw water of these waterworks are from 85 Bq/l to 300 Bq/l. Average indoor radon concentrations exceeding 17,000 Bq/m 3 have been measured in Ludvika with peaks of almost 37,000 Bq/m 3 . In Kolbaeck radon concentrations up to 56,000 Bq/m 3 have been measured. It is quite possible that employees of waterworks can receive doses exceeding 20 mSv per year (calculated according to ICRP:s dose conversion convention). Measurements of radon and gamma radiation from the waterworks are reported and methods to lower the indoor radon concentrations are discussed. (author)

  13. 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.

  14. 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.

  15. 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.

  16. Adequate plasma drug concentrations suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps.

    Science.gov (United States)

    Arensdorff, Lyne; Boillat-Blanco, Noémie; Decosterd, Laurent; Buclin, Thierry; de Vallière, Serge

    2017-09-01

    Elastomeric pumps can be useful for the administration of antibiotics in the outpatient setting. To determine amoxicillin degradation in elastomeric pumps, as well as the effectiveness of amoxicillin treatment administered by elastomeric pumps. Antibiotic degradation was measured in elastomeric pumps filled with 6 g of amoxicillin in 240 mL of NaCl 0.9% by drawing samples at 12 h intervals when stored in the fridge for 48 h and when worn around the waist for 24 h. Subsequently nine patients were treated with continuous infusions of 8 or 12 g of amoxicillin per day. Plasma amoxicillin concentrations were measured on each visit to the outpatient parenteral antibiotic therapy unit. Clinical outcome was verified 3 months after the end of treatment. Amoxicillin degradation in elastomeric pumps reached 10% after 48 h in the fridge and an additional 30% when worn around the waist for 24 h. Mean plasma drug concentrations achieved with 12 g of amoxicillin per day were 18.5 mg/L (95% CI 13.5-23.5), which is largely above the MIC of amoxicillin-susceptible bacteria. Nine patients treated for various complicated infections were cured and had no unexpected adverse effects. Adequate plasma drug concentrations and favourable clinical outcomes suggest that amoxicillin can be administered by continuous infusion using elastomeric pumps. This treatment modality does not fulfil formal requirements regarding pharmaceutical stability, but the resulting safety impact in patients is probably limited. Therapeutic drug monitoring and a close clinical follow-up are recommended if this route of administration is chosen. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. Denitrification of fertilizer wastewater at high chloride concentration

    DEFF Research Database (Denmark)

    Ucisik, Ahmed Süheyl; Henze, Mogens

    Wastewater from fertilizer industry is characterized by high contents of chloride concentration, which normally vary between 60 and 76 g/l. Experiments with bilogical denitrification were performed in lab-scale "fill and draw" reactors with synthetic wastewater with chloride concentrations up to 77.......4 g/l. The results of the experiments showed that biological denitrification was feasible at the extreme environmental conditions prevailing in fertilizer wastewater. Stable continuous biological denitrfication of the synthetic high chloride wastewater was performed up to 77.4 g Cl/l at 37 degree C...

  18. Atmospheric conditions during high ragweed pollen concentrations in Zagreb, Croatia

    Science.gov (United States)

    Prtenjak, Maja Telišman; Srnec, Lidija; Peternel, Renata; Madžarević, Valentina; Hrga, Ivana; Stjepanović, Barbara

    2012-11-01

    We examined the atmospheric conditions favourable to the occurrence of maximum concentrations of ragweed pollen with an extremely high risk of producing allergy. Over the 2002-2009 period, daily pollen data collected in Zagreb were used to identify two periods of high pollen concentration (> 600 grains/m3) for our analysis: period A (3-4 September 2002) and period B (6-7 September 2003). Synoptic conditions in both periods were very similar: Croatia was under the influence of a lower sector high pressure system moving slowly eastward over Eastern Europe. During the 2002-2009 period, this type of weather pattern (on ~ 70% of days), in conjunction with almost non-gradient surface pressure conditions in the area (on ~ 30% of days) characterised days when the daily pollen concentrations were higher than 400 grains/m3. Numerical experiments using a mesoscale model at fine resolution showed successful multi-day simulations reproducing the local topographic influence on wind flow and in reasonable agreement with available observations. According to the model, the relatively weak synoptic flow (predominantly from the eastern direction) allowed local thermal circulations to develop over Zagreb during both high pollen episodes. Two-hour pollen concentrations and 48-h back-trajectories indicated that regional-range transport of pollen grains from the central Pannonian Plain was the cause of the high pollen concentrations during period A. During period B, the north-westward regional-range transport in Zagreb was supplemented significantly by pronounced horizontal recirculation of pollen grains. This recirculation happened within the diurnal local circulation over the city, causing a late-evening increase in pollen concentration.

  19. Polyaspartic Acid Concentration Controls the Rate of Calcium Phosphate Nanorod Formation in High Concentration Systems

    Energy Technology Data Exchange (ETDEWEB)

    Krogstad, Daniel V. [Biosystems and; Wang, Dongbo [Biosystems and; Lin-Gibson, Sheng [Biosystems and

    2017-08-31

    Polyelectrolytes are known to greatly affect calcium phosphate (CaP) mineralization. The reaction kinetics as well as the CaP phase, morphology and aggregation state depend on the relative concentrations of the polyelectrolyte and the inorganic ions in a complex, nonlinear manner. This study examines the structural evolution and kinetics of polyaspartic acid (pAsp) directed CaP mineralization at high concentrations of polyelectrolytes, calcium, and total phosphate (19–30 mg/mL pAsp, 50–100 mM Ca2+, Ca/P = 2). Using a novel combination of characterization techniques including cryogenic transmission electron microscopy (cryo-TEM), spectrophotometry, X-ray total scattering pair distribution function analysis, and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), it was determined that the CaP mineralization occurred over four transition steps. The steps include the formation of aggregates of pAsp stabilized CaP spherical nanoparticles (sNP), crystallization of sNP, oriented attachment of the sNP into nanorods, and further crystallization of the nanorods. The intermediate aggregate sizes and the reaction kinetics were found to be highly polymer concentration dependent while the sizes of the particles were not concentration dependent. This study demonstrates the complex role of pAsp in controlling the mechanism as well as the kinetics of CaP mineralization.

  20. High-concentration planar microtracking photovoltaic system exceeding 30% efficiency

    Science.gov (United States)

    Price, Jared S.; Grede, Alex J.; Wang, Baomin; Lipski, Michael V.; Fisher, Brent; Lee, Kyu-Tae; He, Junwen; Brulo, Gregory S.; Ma, Xiaokun; Burroughs, Scott; Rahn, Christopher D.; Nuzzo, Ralph G.; Rogers, John A.; Giebink, Noel C.

    2017-08-01

    Prospects for concentrating photovoltaic (CPV) power are growing as the market increasingly values high power conversion efficiency to leverage now-dominant balance of system and soft costs. This trend is particularly acute for rooftop photovoltaic power, where delivering the high efficiency of traditional CPV in the form factor of a standard rooftop photovoltaic panel could be transformative. Here, we demonstrate a fully automated planar microtracking CPV system 660× concentration ratio over a 140∘ full field of view. In outdoor testing over the course of two sunny days, the system operates automatically from sunrise to sunset, outperforming a 17%-efficient commercial silicon solar cell by generating >50% more energy per unit area per day in a direct head-to-head competition. These results support the technical feasibility of planar microtracking CPV to deliver a step change in the efficiency of rooftop solar panels at a commercially relevant concentration ratio.

  1. Citalopram and escitalopram plasma drug and metabolite concentrations: genome-wide associations.

    Science.gov (United States)

    Ji, Yuan; Schaid, Daniel J; Desta, Zeruesenay; Kubo, Michiaki; Batzler, Anthony J; Snyder, Karen; Mushiroda, Taisei; Kamatani, Naoyuki; Ogburn, Evan; Hall-Flavin, Daniel; Flockhart, David; Nakamura, Yusuke; Mrazek, David A; Weinshilboum, Richard M

    2014-08-01

    Citalopram (CT) and escitalopram (S-CT) are among the most widely prescribed selective serotonin reuptake inhibitors used to treat major depressive disorder (MDD). We applied a genome-wide association study to identify genetic factors that contribute to variation in plasma concentrations of CT or S-CT and their metabolites in MDD patients treated with CT or S-CT. Our genome-wide association study was performed using samples from 435 MDD patients. Linear mixed models were used to account for within-subject correlations of longitudinal measures of plasma drug/metabolite concentrations (4 and 8 weeks after the initiation of drug therapy), and single-nucleotide polymorphisms (SNPs) were modelled as additive allelic effects. Genome-wide significant associations were observed for S-CT concentration with SNPs in or near the CYP2C19 gene on chromosome 10 (rs1074145, P = 4.1 × 10(-9) ) and with S-didesmethylcitalopram concentration for SNPs near the CYP2D6 locus on chromosome 22 (rs1065852, P = 2.0 × 10(-16) ), supporting the important role of these cytochrome P450 (CYP) enzymes in biotransformation of citalopram. After adjustment for the effect of CYP2C19 functional alleles, the analyses also identified novel loci that will require future replication and functional validation. In vitro and in vivo studies have suggested that the biotransformation of CT to monodesmethylcitalopram and didesmethylcitalopram is mediated by CYP isozymes. The results of our genome-wide association study performed in MDD patients treated with CT or S-CT have confirmed those observations but also identified novel genomic loci that might play a role in variation in plasma levels of CT or its metabolites during the treatment of MDD patients with these selective serotonin reuptake inhibitors. © 2014 The British Pharmacological Society.

  2. Beryllium-10 concentrations in water samples of high northern latitudes

    Energy Technology Data Exchange (ETDEWEB)

    Strobl, C.; Eisenhauer, A.; Schulz, V.; Baumann, S.; Mangini, A. [Heidelberger Akademie der Wissenschaften, Heildelberg (Germany); Kubik, P.W. [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1997-09-01

    {sup 10}Be concentrations in the water column of high northern latitudes were not available so far. We present different {sup 10}Be profiles from the Norwegian-Greenland Sea, the Arctic Ocean, and the Laptev Sea. (author) 3 fig., 3 refs.

  3. Effects of high concentration of chromium stress on physiological ...

    African Journals Online (AJOL)

    We studied the effects of high concentration of chromium (Cr) stress on physiological and biochemical characters and accumulation of Cr in Pingyang Tezao tea [Camellia sinensis (L) O. Kutze 'Pingyangtezao'] through a pot experiment. The results show that the indicators of photosynthesis were all suppressed with ...

  4. The virucidal spectrum of a high concentration alcohol mixture

    NARCIS (Netherlands)

    van Engelenburg, F. A. C.; Terpstra, F. G.; Schuitemaker, H.; Moorer, W. R.

    2002-01-01

    The virucidal spectrum of a high concentration alcohol mixture (80% ethanol and 5% isopropanol) was determined for a broad series of lipid-enveloped (LE) and non-lipid-enveloped (NLE) viruses covering all relevant blood-borne viruses. LE viruses were represented by human immunodeficiency virus

  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. 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...

  8. Rheological behavior of high-concentration sodium caseinate dispersions.

    Science.gov (United States)

    Loveday, Simon M; Rao, M Anandha; Creamer, Lawrence K; Singh, Harjinder

    2010-03-01

    Apparent viscosity and frequency sweep (G', G'') data for sodium caseinate dispersions with concentrations of approximately 18% to 40% w/w were obtained at 20 degrees C; colloidal glass behavior was exhibited by dispersions with concentration >or=23% w/w. The high concentrations were obtained by mixing frozen powdered buffer with sodium caseinate in boiling liquid nitrogen, and allowing the mixtures to thaw and hydrate at 4 degrees C. The low-temperature G'-G'' crossover seen in temperature scans between 60 and 5 degrees C was thought to indicate gelation. Temperature scans from 5 to 90 degrees C revealed gradual decrease in G' followed by plateau values. In contrast, G'' decreased gradually and did not reach plateau values. Increase in hydrophobicity of the sodium caseinate or a decrease in the effective volume fraction of its aggregates may have contributed to these phenomena. The gelation and end of softening temperatures of the dispersions increased with the concentration of sodium caseinate. From an Eldridge-Ferry plot, the enthalpy of softening was estimated to be 29.6 kJ mol(-1). The results of this study should be useful for creating new products with high concentrations of sodium caseinate.

  9. Investigation of the areas of high radon concentration in Gyeongju

    International Nuclear Information System (INIS)

    Lee, Jung Min; Park, Chan Hee; Kim, Shin Jae; Moon, Joo Hyun

    2013-01-01

    The aim of this study was to survey the radon concentrations at 21 elementary schools in Gyeongju, Republic of Korea, to identify those schools with high radon concentrations. Considering their geological characteristics and the preliminary survey results, three schools were finally placed under close scrutiny. For these three schools, continuous measurements over 48 h were taken at the principal's and administration office. The radon concentrations at one school, Naenam, exceeded the action level (148 Bq/m 3 ) established by the U.S. EPA, while those at the other two schools were below that level. - Highlights: • Preliminary measurements of the indoor radon concentrations were performed at the auditoriums in 23 elementary schools in Gyeongju. • Considering the geological characteristics and preliminary survey results, three elementary schools were screened for closer scrutiny. • For the three schools, continuous measurements were made at their principal's and administration offices over 48-h period. • The scrutiny revealed one elementary school of high radon concentration much higher than the U.S. EPA action level

  10. Unphysiologically high magnesium concentrations support chondrocyte proliferation and redifferentiation.

    Science.gov (United States)

    Feyerabend, Frank; Witte, Frank; Kammal, Michael; Willumeit, Regine

    2006-12-01

    The effect of unphysiologically high extracellular magnesium concentrations on chondrocytes, induced by the supplementation of magnesium sulfate, was studied using a 3-phase tissue engineering model. The experiments showed that chondrocyte proliferation and redifferentiation, on the gene and protein expression level, are enhanced. A negative influence was found during chondrogenesis where an inhibition of extracellular matrix formation was observed. In addition, a direct impact on chondrocyte metabolism, elevated magnesium concentrations also affected growth factor effectiveness by consecutive influences during chondrogenesis. All observations were dosage dependent. The results of this study indicate that magnesium may be a useful tool for cartilage tissue engineering.

  11. A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; van den Berg, Dirk-Jan; Hartman, Robin; van den Brink, Willem; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Bakshi, Suruchi; Aranzana-Climent, Vincent; Marchand, Sandrine; Dahyot-Fizelier, Claire; Couet, William; Danhof, Meindert; van Hasselt, Johan G. C.; de lange, Elizabeth C. M.

    Purpose Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the pharmacokinetics in brain compartments, and apply this model to predict human

  12. Highly concentrated zinc oxide nanocrystals sol with strong blue emission

    International Nuclear Information System (INIS)

    Vafaee, M.; Sasani Ghamsari, M.; Radiman, S.

    2011-01-01

    Highly concentrated ZnO sol was synthesized by an improved sol-gel method. Water was used as a modifier to control the sol-gel reaction and provide a way to increase the sol concentration. Concentration of ZnO in the prepared sol is higher than from other methods. Optical absorption and photoluminescence were used to investigate optical properties of the prepared sol. FTIR test was performed to study the influence of water on the compounds of as-prepared sol. The size and morphology of ZnO nanoparticles have been studied by HRTEM. The prepared colloidal ZnO nanocrystals have narrow size distribution (5-8 nm) and showed strong blue emission. The prepared sol has enough potential for optoelectronic applications. - Research highlights: → Novel sol-gel route has been employed to prepare highly concentrated ZnO colloidal nanocrystals. → Water has been used to control the sources of emission in synthesized material. → A strong blue luminescent material has been obtained.

  13. Concentration and drug prices in the retail market for malaria treatment in rural Tanzania.

    Science.gov (United States)

    Goodman, Catherine; Kachur, S Patrick; Abdulla, Salim; Bloland, Peter; Mills, Anne

    2009-06-01

    The impact of market concentration has been little studied in markets for ambulatory care in the developing world, where the retail sector often accounts for a high proportion of treatments. This study begins to address this gap through an analysis of the consumer market for malaria treatment in rural areas of three districts in Tanzania. We developed methods for investigating market definition, sales volumes and concentration, and used these to explore the relationship between antimalarial retail prices and competition.The market was strongly geographically segmented and highly concentrated in terms of antimalarial sales. Antimalarial prices were positively associated with market concentration. High antimalarial prices were likely to be an important factor in the low proportion of care-seekers obtaining appropriate treatment.Retail sector distribution of subsidised antimalarials has been proposed to increase the coverage of effective treatment, but this analysis indicates that local market power may prevent such subsidies from being passed on to rural customers. Policymakers should consider the potential to maintain lower retail prices by decreasing concentration among antimalarial providers and recommending retail price levels. Copyright (c) 2009 John Wiley & Sons, Ltd.

  14. Nonfaradaic nanoporous electrochemistry for conductometry at high electrolyte concentration.

    Science.gov (United States)

    Bae, Je Hyun; Kang, Chung Mu; Choi, Hyoungseon; Kim, Beom Jin; Jang, Woohyuk; Lim, Sung Yul; Kim, Hee Chan; Chung, Taek Dong

    2015-02-17

    Nanoporous electrified surfaces create a unique nonfaradaic electrochemical behavior that is sensitively influenced by pore size, morphology, ionic strength, and electric field modulation. Here, we report the contributions of ion concentration and applied ac frequency to the electrode impedance through an electrical double layer overlap and ion transport along the nanopores. Nanoporous Pt with uniform pore size and geometry (L2-ePt) responded more sensitively to conductivity changes in aqueous solutions than Pt black with poor uniformity despite similar real surface areas and enabled the previously difficult quantitative conductometry measurements at high electrolyte concentrations. The nanopores of L2-ePt were more effective in reducing the electrode impedance and exhibited superior linear responses to not only flat Pt but also Pt black, leading to successful conductometric detection in ion chromatography without ion suppressors and at high ionic strengths.

  15. 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

  16. Biodegradation studies of oil sludge containing high hydrocarbons concentration

    International Nuclear Information System (INIS)

    Olguin-Lora, P.; Munoz-Colunga, A.; Castorena-Cortes, G.; Roldan-Carrillo, T.; Quej Ake, L.; Reyes-Avila, J.; Zapata-Penasco, I.; Marin-Cruz, J.

    2009-01-01

    Oil industry has a significant impact on environment due to the emission of, dust, gases, waste water and solids generated during oil production all the way to basic petrochemical product manufacturing stages. the aim of this work was to evaluate the biodegradation of sludge containing high hydrocarbon concentration originated by a petroleum facility. A sludge sampling was done at the oil residuals pool (ORP) on a gas processing center. (Author)

  17. Effects of high nitrogen concentrations on the growth of submersed macrophytes at moderate phosphorus concentrations.

    Science.gov (United States)

    Yu, Qing; Wang, Hong-Zhu; Li, Yan; Shao, Jian-Chun; Liang, Xiao-Min; Jeppesen, Erik; Wang, Hai-Jun

    2015-10-15

    Eutrophication of lakes leading to loss of submersed macrophytes and higher turbidity is a worldwide phenomenon, attributed to excessive loading of phosphorus (P). However, recently, the role of nitrogen (N) for macrophyte recession has received increasing attention. Due to the close relationship between N and P loading, disentanglement of the specific effects of these two nutrients is often difficult, and some controversy still exists as to the effects of N. We studied the effects of N on submersed macrophytes represented by Vallisneria natans (Lour.) Hara in pots positioned at three depths (0.4 m, 0.8 m, and 1.2 m to form a gradient of underwater light conditions) in 10 large ponds having moderate concentrations of P (TP 0.03 ± 0.04 mg L(-1)) and five targeted concentrations of total nitrogen (TN) (0.5, 2, 10, 20, and 100 mg L(-1)), there were two ponds for each treatment. To study the potential shading effects of other primary producers, we also measured the biomass of phytoplankton (ChlaPhyt) and periphyton (ChlaPeri) expressed as chlorophyll a. We found that leaf length, leaf mass, and root length of macrophytes declined with increasing concentrations of TN and ammonium, while shoot number and root mass did not. All the measured growth indices of macrophytes declined significantly with ChlaPhyt, while none were significantly related to ChlaPeri. Neither ChlaPhyt nor ChlaPeri were, however, significantly negatively related to the various N concentrations. Our results indicate that shading by phytoplankton unrelated to the variation in N loading and perhaps toxic stress exerted by high nitrogen were responsible for the decline in macrophyte growth. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. 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...

  19. Practical design constraints for using secondary concentrators at high temperatures

    Energy Technology Data Exchange (ETDEWEB)

    O' Gallagher, J.J.; Winston, R.

    1999-07-01

    The optical advantages of using nonimaging secondary concentrators in two-stage solar thermal dish systems are well understood. However, practical questions having to do with the thermal behavior of any secondary and its possible effects on the performance of cavity type receivers have only recently begun to be investigated. A few years ago an experimental demonstration of a trumpet type nonimaging secondary concentrator was carried out with a cavity receiver operating 660 C in combination with the Cummins Power Generation CPG-460 7.5 kWe concentrator system. Lessons learned from this and previous experiments are reviewed. The tests alleviated any operational concerns about the effectiveness of active water cooling and have shown that secondaries can be operated successfully at high temperatures without significant problems. There was no evidence of direct heat loss from the hot receiver to the cooled trumpet. The optical quality of any primary can be expected to fall well below design goals and to deteriorate further with time. This expectation should be taken into account in planning future experiments and developing new concentrating systems.

  20. Fabrication procedures for manufacturing high uranium concentration dispersion fuel elements

    International Nuclear Information System (INIS)

    Souza, J.A.B.; Durazzo, M.

    2010-01-01

    IPEN developed and made available for routine production the technology for manufacturing dispersion type fuel elements for use in research reactors. However, the fuel produced at IPEN is limited to the uranium concentration of 3.0 gU/cm 3 by using the U 3 Si 2 -Al dispersion. Increasing the uranium concentration of the fuel is interesting by the possibility of increasing the reactor core reactivity and lifetime of the fuel. It is possible to increase the concentration of uranium in the fuel up to the technological limit of 4.8 gU/cm 3 for the U 3 Si 2 -Al dispersion, which is well placed around the world. This new fuel will be applicable in the new Brazilian-Multipurpose Reactor RMB. This study aimed to develop the manufacturing process of high uranium concentration fuel, redefining the procedures currently used in the manufacture of IPEN. This paper describes the main procedures adjustments that will be necessary. (author)

  1. Fabrication procedures for manufacturing high uranium concentration dispersion fuel elements

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Jose Antonio Batista de; Durazzo, Michelangelo, E-mail: jasouza@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    IPEN developed and made available for routine production the technology for manufacturing dispersion type fuel elements for use in research reactors. However, the fuel produced at IPEN is limited to the uranium concentration of 3.0 g U/c m3 by using the U{sub 3}Si{sub 2}-Al dispersion. Increasing the uranium concentration of the fuel is interesting by the possibility of increasing the reactor core reactivity and lifetime of the fuel. It is possible to increase the concentration of uranium in the fuel up to the technological limit of 4.8 g U/c m3 for the U{sub 3}Si{sub 2}-Al dispersion, which is well placed around the world. This new fuel will be applicable in the new Brazilian- Multipurpose Reactor RMB. This study aimed to develop the manufacturing process of high uranium concentration fuel, redefining the procedures currently used in the manufacture of IPEN. This paper describes the main procedures adjustments that will be necessary. (author)

  2. 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.

  3. Liver imaging with MDCT and high concentration contrast media

    International Nuclear Information System (INIS)

    Spielmann, Audrey L.

    2003-01-01

    Liver imaging has advanced greatly over the last 10 years with helical CT capability and more recently the addition of multidetector-row CT (MDCT). Multidetector CT technology facilitates imaging at faster speeds with improved image quality and less breathing artifact [Abdom. Imaging 25 (2000) 643]. Exquisite three-dimensional data sets can be obtained with thin collimation providing improved lesion detection, multiplanar imaging, and the ability to perform CT angiography of the liver and mesenteric vessels. New challenges arise with this advance in technology including safety considerations. The radiation dose to the patient has increased with MDCT and this is compounded by the ability to perform multi-phase liver imaging. Furthermore, issues of contrast media administration require reconsideration including optimal timing and rate of administration, the total volume of contrast needed and the ideal iodine concentration of the contrast media. Recently, the use of high concentration contrast media (HCCM) has been explored and study results to date will be reviewed

  4. [Condition optimization for bio-oxidation of high-S and high-As gold concentrate].

    Science.gov (United States)

    Yang, Caiyun; Dong, Bowen; Wang, Meijun; Ye, Zhiyong; Zheng, Tianling; Huang, Huaiguo

    2015-12-04

    To study the effects of temperature and lixivium return on the concentrate bio-oxidation and rate of gold cyanide leaching. The bioleaching of a high-sulphur (S) and high-arsenic (As) refractory gold concentrate was conducted, and we studied the effects of different temperature (40 ° and 45 °C) and lixivium return (0 and 600 mL) on the bio-oxidation efficiency. The bacterial community structure also was investigated by 16S rRNA gene clone library. The results showed that both the temperature and lixivium return significantly influenced the oxidation system. The temperature rising elevated the oxidation level, while the addition of lixivium depressed the oxidation. Dissimilarity and DCA (detrended correspondence analysis) indicated the effect of temperature on oxidation system was much greater than lixivium. The bacterial community was comprised by Acidithiocacillus caldu (71%) Leptospirillum ferriphilum (23%) and Sulfobacillus thermosulfidooxidans (6%) indicated by the clone library, and the OTU coverage based on 97% sequence similarity was as high as 93.67%. Temperature rising to 45 T would improve the oxidation efficiency while lixivium return would decrease it. This study is helpful to provide an important guiding value for the industry cost optimization of mesophile bacterial oxidation and reduction process.

  5. Fabrication procedures for manufacturing high uranium concentration dispersion fuel elements

    International Nuclear Information System (INIS)

    Souza, Jose Antonio Batista de

    2011-01-01

    IPEN-CNEN/SP developed the technology to produce the dispersion type fuel elements for research reactors and made it available for routine production. Today, the fuel produced in IPEN-CNEN/SP is limited to the uranium concentration of 3.0 gU/cm 3 for U 3 Si 2 -Al dispersion-based and 2.3 gU/cm 3 for U 3 O 8 -Al dispersion. The increase of uranium concentration in fuel plates enables the reactivity of the reactor core reactivity to be higher and extends the fuel life. Concerning technology, it is possible to increase the uranium concentration in the fuel meat up to the limit of 4.8 gU/cm 3 in U 3 Si 2 -Al dispersion and 3.2 gU/cm 3 U 3 O 8 -Al dispersion. These dispersions are well qualified worldwide. This work aims to develop the manufacturing process of both fuel meats with high uranium concentrations, by redefining the manufacturing procedures currently adopted in the Nuclear Fuel Center of IPEN-CNEN/SP. Based on the results, it was concluded that to achieve the desired concentration, it is necessary to make some changes in the established procedures, such as in the particle size of the fuel powder and in the feeding process inside the matrix, before briquette pressing. These studies have also shown that the fuel plates, with a high concentration of U 3 Si 2 -Al, met the used specifications. On the other hand, the appearance of the microstructure obtained from U 3 O 8 -Al dispersion fuel plates with 3.2 gU/cm 3 showed to be unsatisfactory, due to the considerably significant porosity observed. The developed fabrication procedure was applied to U 3 Si 2 production at 4.8 gU/cm 3 , with enriched uranium. The produced plates were used to assemble the fuel element IEA-228, which was irradiated in order to check its performance in the IEA-R1 reactor at IPEN-CNEN/SP. These new fuels have potential to be used in the new Brazilian Multipurpose Reactor - RMB. (author)

  6. Mitigation of houses with extremely high indoor radon concentrations

    International Nuclear Information System (INIS)

    Jiranek, M.; Neznal, M.

    2006-01-01

    Full text of publication follows: The paper reports on the experience of the Czech Technical University in dealing with mitigation of houses in which unusually high indoor radon concentrations were found. The whole process of remediation is illustrated by example of an old single-family house that was built in the area formed by highly permeable soils with high radon content in the soil air. T he house has a small cellar located under 1/5 of the ground floor area. Two types of floors, i.e. timber floors and cracked concrete slabs were found in the house. As a result of extremely high radon concentration in the sub-floor region (up to 600 kBq/m 3 ) and leaky structures in contact with soil, radon concentrations around 100 kBq/m 3 in the cellar and up to 60 kBq/m 3 in the living rooms on the ground floor were measured prior to mitigation. Mitigation measures that were carried out in the house consist of reconstruction of timber floors and installation of active soil depressurization. Timber floors were replaced with concrete slab fitted with damp proof membrane, thermal insulation and floor covering. The soil depressurization system was made up of two sections. The first section is composed of the network of perforated pipes inserted in the drainage layer placed under the new floors and four perforated tubes drilled under the existing floors. The soil air from this section is extracted by means of a roof fan installed at the top of the vertical exhaust pipe running inside the living space and terminating above the roof. The second section was designed to withdraw by means of a small fan radon-laden air from the filling in the floor above the cellar and from perforated tubes drilled into the sub-floor region under the rooms adjacent to the cellar. It serves also for the active ventilation of the cellar. Pressure, temperature and radon concentration sensors were installed into the drainage layer during the reconstruction of floors to record variations in these

  7. Introduction of high oxygen concentrations into silicon wafers by high-temperature diffusion

    International Nuclear Information System (INIS)

    Casse, G.; Glaser, M.; Lemeilleur, F.; Ruzin, A.; Wegrzecki, M.

    1999-01-01

    The tolerance of silicon detectors to hadron irradiation can be improved by the introduction of a high concentration of oxygen into the starting material. High-resistivity Floating-Zone (FZ) silicon is required for detectors used in particle physics applications. A significantly high oxygen concentration (>10 17 atoms cm -3 ) cannot readily be achieved during the FZ silicon refinement. The diffusion of oxygen at elevated temperatures from a SiO 2 layer grown on both sides of a silicon wafer is a simple and effective technique to achieve high and uniform concentrations of oxygen throughout the bulk of a 300 μm thick silicon wafer

  8. Particulate Matter Concentrations in East Oakland's High Street Corridor

    Science.gov (United States)

    Lei, P.; Jackson, J.; Lewis, R.; Marigny, A.; Mitchell, J. D.; Nguyen, R.; Philips, B.; Randle, D.; Romero, D.; Spears, D.; Telles, C.; Weissman, D.

    2012-12-01

    Particulate matter (PM) is a complex mixture of small solid pieces and/or liquid droplets in the air. High concentrations of PM can pose a serious health hazard because inhalation can result in breathing problems and/or aggravate asthma. Long term exposure can increase the likelihood of respiratory problems like asthma and emphysema as well as cancer. The smaller the particles, the deeper they can get into the respiratory system. For this reason, the smallest particles, those smaller than 2.5 micrometers in diameter (PM2.5), are the most dangerous. PM2.5 is largely emitted from motor vehicles burning fuels that don't break down fully. Our research team investigated the levels of PM2.5 as well as particles smaller than 10 micrometers (PM10) and total suspended particulate (TSP) along the northeast-southwest trending High Street Corridor, near Fremont High School in East Oakland, California. Using the Aerocet 531 mass particle counter, team members walked through neighborhoods and along major roads within a 1 mile radius of Fremont High School. The Aerocet 531 recorded two minute average measurements of all the relevant PM sizes, which are reported in mg/m3. Measurements were consistently taken in the morning, between 8:30 and 11:30 am. Preliminary results indicate maximum readings of all PM sizes at sites that are in close proximity to a major freeway (Interstate-880). These results support our initial hypothesis that proximity to major roads and freeways, especially those with high diesel-fuel burning truck traffic, would be the primary factor affecting PM concentration levels. Preliminary median and maximum readings all suggest particulate matter levels below what the EPA would consider unhealthy or risky.

  9. Unexpectedly high ultrafine aerosol concentrations above East Antarctic sea ice

    Directory of Open Access Journals (Sweden)

    R. S. Humphries

    2016-02-01

    Full Text Available Better characterisation of aerosol processes in pristine, natural environments, such as Antarctica, have recently been shown to lead to the largest reduction in uncertainties in our understanding of radiative forcing. Our understanding of aerosols in the Antarctic region is currently based on measurements that are often limited to boundary layer air masses at spatially sparse coastal and continental research stations, with only a handful of studies in the vast sea-ice region. In this paper, the first observational study of sub-micron aerosols in the East Antarctic sea ice region is presented. Measurements were conducted aboard the icebreaker Aurora Australis in spring 2012 and found that boundary layer condensation nuclei (CN3 concentrations exhibited a five-fold increase moving across the polar front, with mean polar cell concentrations of 1130 cm−3 – higher than any observed elsewhere in the Antarctic and Southern Ocean region. The absence of evidence for aerosol growth suggested that nucleation was unlikely to be local. Air parcel trajectories indicated significant influence from the free troposphere above the Antarctic continent, implicating this as the likely nucleation region for surface aerosol, a similar conclusion to previous Antarctic aerosol studies. The highest aerosol concentrations were found to correlate with low-pressure systems, suggesting that the passage of cyclones provided an accelerated pathway, delivering air masses quickly from the free troposphere to the surface. After descent from the Antarctic free troposphere, trajectories suggest that sea-ice boundary layer air masses travelled equatorward into the low-albedo Southern Ocean region, transporting with them emissions and these aerosol nuclei which, after growth, may potentially impact on the region's radiative balance. The high aerosol concentrations and their transport pathways described here, could help reduce the discrepancy currently present between

  10. Unexpectedly high ultrafine aerosol concentrations above East Antarctic sea ice

    Science.gov (United States)

    Humphries, R. S.; Klekociuk, A. R.; Schofield, R.; Keywood, M.; Ward, J.; Wilson, S. R.

    2016-02-01

    Better characterisation of aerosol processes in pristine, natural environments, such as Antarctica, have recently been shown to lead to the largest reduction in uncertainties in our understanding of radiative forcing. Our understanding of aerosols in the Antarctic region is currently based on measurements that are often limited to boundary layer air masses at spatially sparse coastal and continental research stations, with only a handful of studies in the vast sea-ice region. In this paper, the first observational study of sub-micron aerosols in the East Antarctic sea ice region is presented. Measurements were conducted aboard the icebreaker Aurora Australis in spring 2012 and found that boundary layer condensation nuclei (CN3) concentrations exhibited a five-fold increase moving across the polar front, with mean polar cell concentrations of 1130 cm-3 - higher than any observed elsewhere in the Antarctic and Southern Ocean region. The absence of evidence for aerosol growth suggested that nucleation was unlikely to be local. Air parcel trajectories indicated significant influence from the free troposphere above the Antarctic continent, implicating this as the likely nucleation region for surface aerosol, a similar conclusion to previous Antarctic aerosol studies. The highest aerosol concentrations were found to correlate with low-pressure systems, suggesting that the passage of cyclones provided an accelerated pathway, delivering air masses quickly from the free troposphere to the surface. After descent from the Antarctic free troposphere, trajectories suggest that sea-ice boundary layer air masses travelled equatorward into the low-albedo Southern Ocean region, transporting with them emissions and these aerosol nuclei which, after growth, may potentially impact on the region's radiative balance. The high aerosol concentrations and their transport pathways described here, could help reduce the discrepancy currently present between simulations and observations of

  11. Hydrogen concentration and distribution in high-purity germanium crystals

    International Nuclear Information System (INIS)

    Hansen, W.L.; Haller, E.E.; Luke, P.N.

    1981-10-01

    High-purity germanium crystals used for making nuclear radiation detectors are usually grown in a hydrogen ambient from a melt contained in a high-purity silica crucible. The benefits and problems encountered in using a hydrogen ambient are reviewed. A hydrogen concentration of about 2 x 10 15 cm -3 has been determined by growing crystals in hydrogen spiked with tritium and counting the tritium β-decays in detectors made from these crystals. Annealing studies show that the hydrogen is strongly bound, either to defects or as H 2 with a dissociation energy > 3 eV. This is lowered to 1.8 eV when copper is present. Etching defects in dislocation-free crystals grown in hydrogen have been found by etch stripping to have a density of about 1 x 10 7 cm -3 and are estimated to contain 10 8 H atoms each

  12. 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

  13. 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...

  14. Five year results of an international proficiency testing programme for measurement of antifungal drug concentrations

    NARCIS (Netherlands)

    Lempers, V.J.C.; Alffenaar, J.W.C.; Touw, D.J.; Burger, D.M.; Uges, D.R.A.; Aarnoutse, R.E.; Brüggemann, R.J.M.

    2014-01-01

    OBJECTIVES: Since 2007 the Dutch Association for Quality Assessment in Therapeutic Drug Monitoring (KKGT) has organized an international interlaboratory proficiency testing (PT) programme for measurement of antifungal drugs in plasma. We describe the 5 year results of the laboratories' performance.

  15. Evaluation of Flexible Tacrolimus Drug Concentration Monitoring Approach in Patients Receiving Extended-Release Once-Daily Tacrolimus Tablets.

    Science.gov (United States)

    Philosophe, Benjamin; Leca, Nicolae; West-Thielke, Patricia M; Horwedel, Timothy; Culkin-Gemmell, Christine; Kistler, Kristin; Stevens, Daniel R

    2018-02-20

    The majority of United States kidney transplant patients are treated with tacrolimus, a drug effective in preventing graft rejection, but with a narrow therapeutic range, necessitating close monitoring to avoid increased risks of transplant rejection or toxicity if the tacrolimus concentration is too low or too high, respectively. The trough drug concentration tests are time sensitive; patients treated on a twice-daily basis have blood draws exactly 12 hours after their previous dose. The schedule's rigidity causes problems for both patients and health care providers. Novel once-daily tacrolimus formulations such as LCPT (an extended-release tablet by Veloxis Pharmaceuticals, Inc., Cary, North Carolina) have allowed for blood draws on a once-daily basis; however, even that schedule can be restrictive. Results from tests taken either before or after that 24-hour target time may be discarded, or worse, may lead to inappropriate dose changes. Data from ASTCOFF, a phase 3B pharmacokinetic clinical trial (NCT02339246), demonstrated that the unique pharmacokinetic curve of LCPT may allow for a therapeutic monitoring window that extends for 3 hours before or after the 24-hour monitoring target. Furthermore, important tools to help clinicians interpret these levels, such as formulas to estimate the 24-hour trough level if an alternative monitoring time is used, were constructed from these data. These study results give treating clinicians access to data that allow them to safely use and monitor LCPT in their patients and expand the body of evidence surrounding differentiation and practical application of the novel LCPT tacrolimus formulation. © 2018, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

  16. 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.

  17. 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.

  18. Alcohol consumption is associated with high concentrations of urinary hydroxytyrosol.

    Science.gov (United States)

    Schröder, Helmut; de la Torre, Rafael; Estruch, Ramón; Corella, Dolores; Martínez-González, Miguel Angel; Salas-Salvadó, Jordi; Ros, Emilio; Arós, Fernando; Flores, Gemma; Civit, Ester; Farré, Magí; Fiol, Miguel; Vila, Joan; Fernandez-Crehuet, Joaquín; Ruiz-Gutiérrez, Valentina; Lapetra, Jose; Sáez, Guillermo; Covas, María-Isabel

    2009-11-01

    Previously, we reported the presence of hydroxytyrosol in red wine and higher human urinary recovery of total hydroxytyrosol than that expected after a single red wine intake. We hypothesized that the alcohol present in wine could promote endogenous hydroxytyrosol generation. The objective was to assess the relation between alcohol consumption and urinary hydroxytyrosol concentrations. This was a cross-sectional study with baseline data from a subsample of the PREvención con DIeta MEDiterránea (PREDIMED) trial, an intervention study directed at testing the efficacy of the Mediterranean diet on the primary prevention of cardiovascular disease. Participants included 1045 subjects, aged 55-80 y, who were at high cardiovascular risk. Alcohol consumption was estimated through a validated food-frequency questionnaire. Urinary hydroxytyrosol and ethyl glucuronide, a biomarker of alcohol consumption, were measured. Urinary ethyl glucuronide concentrations were directly related to alcohol and wine consumption (P logistic regression analyses showed a significant linear trend (P 20 g (2 drinks)/d and >10 g (1 drink)/d alcohol in men and women, respectively, were associated (P wine as a source of hydroxytyrosol and alcohol as an indirect promoter of endogenous hydroxytyrosol generation. This trial was registered at controlled-trials.com/isrctn/ as ISRCTN 35739639.

  19. Thermal denitration of high concentration nitrate salts waste water

    International Nuclear Information System (INIS)

    Hwang, D. S.; Oh, J. H.; Choi, Y. D.; Hwang, S. T.; Park, J. H.; Latge, C.

    2003-01-01

    This study investigated the thermodynamic and the thermal decomposition properties of high concentration nitrate salts waste water for the lagoon sludge treatment. The thermodynamic property was carried out by COACH and GEMINI II based on the composition of nitrate salts waste water. The thermal decomposition property was carried out by TG-DTA and XRD. Ammonium nitrate and sodium nitrate were decomposed at 250 .deg. C and 730 . deg. C, respectively. Sodium nitrate could be decomposed at 450 .deg. C in the case of adding alumina for converting unstable Na 2 O into stable Na 2 O.Al 2 O 3 . The flow sheet for nitrate salts waste water treatment was proposed based on the these properties data. These will be used by the basic data of the process simulation

  20. Acquisition and Analysis of Data from High Concentration Solutions

    KAUST Repository

    Besong, Tabot M.D.

    2016-05-13

    The problems associated with ultracentrifugal analysis of macromolecular solutions at high (>10 mg/ml) are reviewed. Especially for the case of solutes which are non-monodisperse, meaningful results are not readily achievable using sedimentation velocity approaches. It is shown however by both simulation and analysis of practical data that using a modified form of an algorithm (INVEQ) published in other contexts, sedimentation equilibrium (SE) profiles can be analysed successfully, enabling topics such as oligomer presence or formation to be defined.To achieve this, it is necessary to employ an approach in which the solution density, which in an SE profile is radius-dependent, is taken into consideration. Simulation suggests that any reasonable level of solute concentration can be analysed.

  1. Acquisition and Analysis of Data from High Concentration Solutions

    KAUST Repository

    Besong, Tabot M.D.; Rowe, Arthur J.

    2016-01-01

    The problems associated with ultracentrifugal analysis of macromolecular solutions at high (>10 mg/ml) are reviewed. Especially for the case of solutes which are non-monodisperse, meaningful results are not readily achievable using sedimentation velocity approaches. It is shown however by both simulation and analysis of practical data that using a modified form of an algorithm (INVEQ) published in other contexts, sedimentation equilibrium (SE) profiles can be analysed successfully, enabling topics such as oligomer presence or formation to be defined.To achieve this, it is necessary to employ an approach in which the solution density, which in an SE profile is radius-dependent, is taken into consideration. Simulation suggests that any reasonable level of solute concentration can be analysed.

  2. Characterization of blood donors with high haemoglobin concentration

    DEFF Research Database (Denmark)

    Magnussen, K; Hasselbalch, H C; Ullum, H

    2013-01-01

    Background and Objectives  The literature contains little on the prevalence and causes of high predonation haemoglobin levels among blood donors. This study aimed to characterize and develop an algorithm to manage would-be donors with polycythaemia. Materials and Methods  Between November 2009...... and November 2011, we offered haematology consultations to blood donors with repeated haemoglobin concentration (Hb) above the WHO limit for polycythaemia vera (PV) (10·2 and 11·5 mm/16·5 and 18·5 g/dl for women and men, respectively). Investigation of such donors included Hb, haematocrit, mean cell volume......, erythropoietin, ferritin, platelet count and leucocyte count, JAK2 V617 and JAK2 exon12 analysis, as well as other routine measurements. Results  Among 46 such donors, 39 had a history of smoking, which contributes to erythrocytosis. Two had PV, five had severe hypertension, one of them because of renal artery...

  3. 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...

  4. Highly Concentrated Acetic Acid Poisoning: 400 Cases Reviewed

    Directory of Open Access Journals (Sweden)

    Konstantin Brusin

    2012-12-01

    Full Text Available Background: Caustic substance ingestion is known for causing a wide array of gastrointestinal and systemic complications. In Russia, ingestion of acetic acid is a major problem which annually affects 11.2 per 100,000 individuals. The objective of this study was to report and analyze main complications and outcomes of patients with 70% concentrated acetic acid poisoning. Methods: This was a retrospective study of patients with acetic acid ingestion who were treated at Sverdlovsk Regional Poisoning Treatment Center during 2006 to 2012. GI mucosal injury of each patient was assessed with endoscopy according to Zargar’s scale. Data analysis was performed to analyze the predictors of stricture formation and mortality. Results: A total of 400 patients with median age of 47 yr were included. GI injury grade I was found in 66 cases (16.5%, IIa in 117 (29.3%, IIb in 120 (30%, IIIa in 27 (16.7% and IIIb in 70 (17.5%. 11% of patients developed strictures and overall mortality rate was 21%. Main complications were hemolysis (55%, renal injury (35%, pneumonia (27% and bleeding during the first 3 days (27%. Predictors of mortality were age 60 to 79 years, grade IIIa and IIIb of GI injury, pneumonia, stages “I”, “F” and “L” of kidney damage according to the RIFLE scale and administration of prednisolone. Predictors of stricture formation were ingestion of over 100 mL of acetic acid and grade IIb and IIIa of GI injury. Conclusion: Highly concentrated acetic acid is still frequently ingested in Russia with a high mortality rate. Patients with higher grades of GI injury, pneumonia, renal injury and higher amount of acid ingested should be more carefully monitored as they are more susceptible to develop fatal consequences.          

  5. Plasma methylphenidate concentrations in youths treated with high-dose osmotic release oral system formulation.

    Science.gov (United States)

    Stevens, Jonathan R; George, Robert A; Fusillo, Steven; Stern, Theodore A; Wilens, Timothy E

    2010-02-01

    Children and adolescents are being treated increasingly for attention-deficit/hyperactivity disorder (ADHD) with a variety of stimulants in higher than Food and Drug Administration (FDA)-approved doses and in combination with other medications. We sought to determine methylphenidate (MPH) concentrations in children and adolescents treated with high-dose, extended-release osmotic release oral system (OROS) MPH plus concomitant medications, and to examine MPH concentrations with respect to the safety and tolerability of treatment. Plasma MPH concentrations were measured by liquid chromatography-mass spectrometry 4-5 hours after administration of medication in a sample of youths diagnosed with ADHD. These youths were treated naturalistically with higher than FDA-approved doses of OROS MPH in addition to their concomitant medications. Markers of safety and tolerability (e.g., measures of blood pressure and heart rate) were also examined. Among the 17 patients (with a mean age of 16.2 +/- 2 years and a mean number of concurrent medications of 2.23 +/- 0.94), the mean plasma MPH concentration was 28 +/- 9.1 ng/mL, despite a mean daily dose of OROS MPH of 169 +/- 5 mg (3.0 +/- 0.8 mg/kg per day). No patient had a plasma MPH level >or=50 ng/mL or clinical signs of stimulant toxicity. No correlation was found between plasma MPH concentrations and OROS MPH dose or changes in vital signs. High-dose OROS MPH, used in combination with other medications, was not associated with either unusually elevated plasma MPH concentrations or with clinically meaningful changes in vital signs. Study limitations include a single time-point sampling of MPH concentrations, a small sample size, and a lack of outcome measures to address treatment effectiveness.

  6. 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.

  7. Acetate biodegradation by anaerobic microorganisms at high pH and high calcium concentration

    International Nuclear Information System (INIS)

    Yoshida, Takahiro

    2011-01-01

    Acetate biodegradation at a high pH and a high calcium concentration was examined to clarify the effect of bacterial activity on the migration of organic 14 C compounds in cementitious repositories. Tamagawa river sediment or Teganuma pond sediment was anaerobically cultured with 5 mM acetate and 10 mM nitrate at pH 9.5-12 at 30 o C. After 20 and 90 days, the acetate concentration of the culture medium was analyzed and found to have decreased below 5 mM at pH ≤ 11. On the other hand, it did not decrease when either sediment was incubated in the absence of nitrate. These results suggest that nitrate-reducing bacteria can biodegrade acetate under more alkaline conditions than the reported pH range in which nitrate-reducing bacteria can exhibit activity. Acetate biodegradation was also examined at a high calcium concentration. Sediments were anaerobically cultured at pH 9.5 with 5 mM acetate and 10 mM nitrate in solution, equilibrated with ordinary Portland cement hydrate, in which the Ca concentration was 14.6 mM. No decrease in acetate concentration after incubation of the sediments was observed, nor was it lower than in the absence of cementitious composition, suggesting that kinetics of acetate biodegradation by anaerobic microorganisms is lowered by a high Ca concentration. - Research highlights: → Acetate biodegradation at a high pH and a high calcium concentration was examined to clarify the effect of bacterial activity on the migration of organic 14 C compounds in cementitious repositories. → Nitrate-reducing bacteria can biodegrade acetate at pH ≤ 11. → Kinetics of acetate biodegradation by anaerobic microorganisms might be lowered by a high Ca concentration.

  8. Modelling acceptance of sunlight in high and low photovoltaic concentration

    Energy Technology Data Exchange (ETDEWEB)

    Leutz, Ralf, E-mail: ralf.leutz@leopil.com [Leutz Optics and Illumination UG (haftungsbeschränkt), Marburg (Germany)

    2014-09-26

    A simple model incorporating linear radiation characteristics, along with the optical trains and geometrical concentration ratios of solar concentrators is presented with performance examples for optical trains of HCPV, LCPV and benchmark flat-plate PV.

  9. Modelling acceptance of sunlight in high and low photovoltaic concentration

    Science.gov (United States)

    Leutz, Ralf

    2014-09-01

    A simple model incorporating linear radiation characteristics, along with the optical trains and geometrical concentration ratios of solar concentrators is presented with performance examples for optical trains of HCPV, LCPV and benchmark flat-plate PV.

  10. Modelling acceptance of sunlight in high and low photovoltaic concentration

    International Nuclear Information System (INIS)

    Leutz, Ralf

    2014-01-01

    A simple model incorporating linear radiation characteristics, along with the optical trains and geometrical concentration ratios of solar concentrators is presented with performance examples for optical trains of HCPV, LCPV and benchmark flat-plate PV

  11. Metamaterial Receivers for High Efficiency Concentrated Solar Energy Conversion

    Energy Technology Data Exchange (ETDEWEB)

    Yellowhair, Julius E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Concentrating Solar Technologies Dept.; Kwon, Hoyeong [Univ. of Texas, Austin, TX (United States). Dept. of Electrical and Computer Engineering; Alu, Andrea [Univ. of Texas, Austin, TX (United States). Dept. of Electrical and Computer Engineering; Jarecki, Robert L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Concentrating Solar Technologies Dept.; Shinde, Subhash L. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States). Concentrating Solar Technologies Dept.

    2016-09-01

    Operation of concentrated solar power receivers at higher temperatures (>700°C) would enable supercritical carbon dioxide (sCO2) power cycles for improved power cycle efficiencies (>50%) and cost-effective solar thermal power. Unfortunately, radiative losses at higher temperatures in conventional receivers can negatively impact the system efficiency gains. One approach to improve receiver thermal efficiency is to utilize selective coatings that enhance absorption across the visible solar spectrum while minimizing emission in the infrared to reduce radiative losses. Existing coatings, however, tend to degrade rapidly at elevated temperatures. In this report, we report on the initial designs and fabrication of spectrally selective metamaterial-based absorbers for high-temperature, high-thermal flux environments important for solarized sCO2 power cycles. Metamaterials are structured media whose optical properties are determined by sub-wavelength structural features instead of bulk material properties, providing unique solutions by decoupling the optical absorption spectrum from thermal stability requirements. The key enabling innovative concept proposed is the use of structured surfaces with spectral responses that can be tailored to optimize the absorption and retention of solar energy for a given temperature range. In this initial study through the Academic Alliance partnership with University of Texas at Austin, we use Tungsten for its stability in expected harsh environments, compatibility with microfabrication techniques, and required optical performance. Our goal is to tailor the optical properties for high (near unity) absorptivity across the majority of the solar spectrum and over a broad range of incidence angles, and at the same time achieve negligible absorptivity in the near infrared to optimize the energy absorbed and retained. To this goal, we apply the recently developed concept of plasmonic Brewster angle to suitably designed

  12. 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)

  13. 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)

  14. 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.

  15. Alcoholic fermentation by immobilized yeast at high sugar concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Holcberg, I.B.; Margalith, P.

    1981-01-01

    Glucose fermentation by Saccharomyces cerevisiae immobilized by entrapment in agar, carrageenan, alginate and polyacrylamide gels, was compared to that of freely suspended cells at concentration of 10-50% (w.w.) sugar. The rate of ethanol production by the entrapped cells was 20-25% higher than that of the free cells. Concentrations of up to 14.5% w/w ethanol (30% glucose initial concentration) could be obtained. A number of hypotheses for the improved alcoholic fermentation are discussed.

  16. Cylindrically symmetric Fresnel lens for high concentration photovoltaic

    Science.gov (United States)

    Hung, Yu-Ting; Su, Guo-Dung

    2009-08-01

    High concentration photovoltaic (HCPV) utilizes point-focus cost-effective plastic Fresnel lens. And a millimeter-sized Ill-V compound multi-junction solar cell is placed underneath focusing optics which can achieve cell efficiency potential of up to 40.7 %. The advantage of HCPV makes less solar cell area and higher efficiency; however, the acceptance angle of HCPV is about +/-1°, which is very small and the mechanical tracking of the sun is necessary. In order to reduce the power consumption and the angle tracking error of tracking systems, a light collector model with larger acceptance angle is designed with ZEMAX®. In this model, the original radially symmetric Fresnel lens of HCPV is replaced by cylindrically symmetric Fresnel lens and a parabolic reflective surface. Light is collected in two dimensions separately. And a couple of lenses and a light pipe are added before the solar cell chip in order to collect more light when sun light deviates from incident angle of 00. An acceptance angle of +/-10° is achieved with GCR 400.

  17. 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.

  18. Selection of common bean lines with high grain yield and high grain calcium and iron concentrations

    Directory of Open Access Journals (Sweden)

    Nerinéia Dalfollo Ribeiro

    2014-02-01

    Full Text Available Genetic improvement of common bean nutritional quality has advantages in marketing and can contribute to society as a food source. The objective of this study was to evaluate the genetic variability for grain yield, calcium and iron concentrations in grains of inbred common bean lines obtained by different breeding methods. For this, 136 F7 inbred lines were obtained using the Pedigree method and 136 F7 inbred lines were obtained using the Single-Seed Descent (SSD method. The lines showed genetic variability for grain yield, and concentrations of calcium and iron independently of the method of advancing segregating populations. The Pedigree method allows obtaining a greater number of lines with high grain yield. Selection using the SSD method allows the identification of a larger number of lines with high concentrations of calcium and iron in grains. Weak negative correlations were found between grain yield and calcium concentration (r = -0.0994 and grain yield and iron concentration (r = -0.3926. Several lines show genetic superiority for grain yield and concentrations of calcium and iron in grains and their selection can result in new common bean cultivars with high nutritional quality.

  19. 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

  20. An Automatic High Efficient Method for Dish Concentrator Alignment

    Directory of Open Access Journals (Sweden)

    Yong Wang

    2014-01-01

    for the alignment of faceted solar dish concentrator. The isosceles triangle configuration of facet’s footholds determines a fixed relation between light spot displacements and foothold movements, which allows an automatic determination of the amount of adjustments. Tests on a 25 kW Stirling Energy System dish concentrator verify the feasibility, accuracy, and efficiency of our method.

  1. Starch source in high concentrate rations does not affect rumen pH, histamine and lipopolysaccharide concentrations in dairy cows

    NARCIS (Netherlands)

    Pilachai, R.; Schonewille, J.T.; Thamrongyoswittayakul, C.; Aiumlamai, S.; Wachirapakom, C.; Everts, H.; Hendriks, W.H.

    2012-01-01

    The replacement of ground corn by cassava meal on rumen pH, lipopolysaccharide (LPS) and histamine concentrations under typical Thai feeding conditions (high concentrate diets and rice straw as the sole source of roughage) was investigated. Four rumen-fistulated crossbred Holstein, non-pregnant, dry

  2. Effects of drugs in subtoxic concentrations on the metabolic fluxes in human hepatoma cell line Hep G2

    International Nuclear Information System (INIS)

    Niklas, Jens; Noor, Fozia; Heinzle, Elmar

    2009-01-01

    Commonly used cytotoxicity assays assess the toxicity of a compound by measuring certain parameters which directly or indirectly correlate to the viability of the cells. However, the effects of a given compound at concentrations considerably below EC 50 values are usually not evaluated. These subtoxic effects are difficult to identify but may eventually cause severe and costly long term problems such as idiosyncratic hepatotoxicity. We determined the toxicity of three hepatotoxic compounds, namely amiodarone, diclofenac and tacrine on the human hepatoma cell line Hep G2 using an online kinetic respiration assay and analysed the effects of subtoxic concentrations of these drugs on the cellular metabolism by using metabolic flux analysis. Several changes in the metabolism could be detected upon exposure to subtoxic concentrations of the test compounds. Upon exposure to diclofenac and tacrine an increase in the TCA-cycle activity was observed which could be a signature of an uncoupling of the oxidative phosphorylation. The results indicate that metabolic flux analysis could serve as an invaluable novel tool for the investigation of the effects of drugs. The described methodology enables tracking the toxicity of compounds dynamically using the respiration assay in a range of concentrations and the metabolic flux analysis permits interesting insights into the changes in the central metabolism of the cell upon exposure to drugs.

  3. Effect of Na2SO3 concentration to drug loading and drug release of ascorbic acid in chitosan edible film as drug delivery system membrane

    Directory of Open Access Journals (Sweden)

    Kistriyani Lilis

    2018-01-01

    Full Text Available Chitosan is a type of carbohydrate compounds produced from waste marine products, in particular the class of shrimp, crabs and clams. Chitosan is often process into edible films and utilized for food packaging also has potential as a membrane for drug delivery system. Drug loading and drug release can be controlled by improve the characteristics of the membrane by adding crosslinker. The purpose of this research is to study the effect of addition of crosslinker to the rate of loading and release of ascorbic acid in the chitosan edible film. Na2SO3 was used as crosslinker. Two grams of chitosan was dissolved into 100 ml of distilled water. Acetic acid and plasticizer were added in the solution then heated at 50°C. Na2SO3 solution with mass various of Na2SO3 dissolved, 01026 0.3; and 0.5 grams were added about 30 mL to make edible film. The analysis include of drug loading, drug release and tensile strength. The result showed that the loading of edible film with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 60.98 ppm; 52.53 ppm; and 40.88 ppm, meanwhile for the release with crosslinker 0.15 g; 0.3 g; and 0.5 g respectively were 3.78 ppm; 5.72 ppm; and 5.97 ppm.

  4. A high-gain, compact, nonimaging concentrator: RXI.

    Science.gov (United States)

    Miñano, J C; Gonźlez, J C; Benítez, P

    1995-12-01

    The design procedure of a new nonimaging concentrator (called an RXI) is explained. Rays that impinge on the concentrator aperture, within the acceptance angle, are directed to the receiver by means of one refraction, one reflection, and one total internal reflection. The concentrator can be made as a single dielectric piece (in which the receiver is immersed) whose aspect ratio (thickness/aperture diameter) is close to 1/3. Ray-tracing analysis of a rotational symmetric RXI shows total transmissions of greater than 94.5% (no absorption or reflection losses are considered) when the acceptance angle of the incoming rays is small (<3°) and when the receiver area is the smallest possible (maximal concentration.).

  5. Intercomparison of passive microwave sea ice concentration retrievals over the high-concentration Arctic sea ice

    DEFF Research Database (Denmark)

    andersen, susanne; Tonboe, R.; Kaleschke, L.

    2007-01-01

    [1] Measurements of sea ice concentration from the Special Sensor Microwave Imager (SSM/I) using seven different algorithms are compared to ship observations, sea ice divergence estimates from the Radarsat Geophysical Processor System, and ice and water surface type classification of 59 wide...... with sensor noise between 1.3 and 1.8%. This is in accord with variability estimated from analysis of SSM/I time series. Algorithms, which primarily use 85 GHz information, consistently give the best agreement with both SAR ice concentrations and ship observations. Although the 85 GHz information is more...... sensitive to atmospheric influences, it was found that the atmospheric contribution is secondary to the influence of the surface emissivity variability. Analysis of the entire SSM/I time series shows that there are significant differences in trend between sea ice extent and area, using different algorithms...

  6. Efficacy of high iodine concentration contrast medium with saline pushing in hepatic CT in patients with chronic liver disease. Comparison of high doses-standard contrast medium concentration

    International Nuclear Information System (INIS)

    Matoba, Munetaka; Kondo, Tamaki; Nishikawa, Takahiro; Kuginuki, Yasuaki; Yokota, Hajime; Higashi, Kotaro; Tonami, Hisao

    2006-01-01

    The aim of this study was to compare the enhancement of liver parenchyama with high iodine concentration contrast medium with saline pushing to that with high doses standard iodine concentration in hepatic CT in patients with chronic liver disease. There was no statistically significant difference regarding to the enhancement of liver parenchyama between the 370 mgI/ml of contrast medium with saline pushing and high doses standard iodine concentration contrast medium. (author)

  7. 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...

  8. 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...

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

    Directory of Open Access Journals (Sweden)

    Katarzyna Głuszek

    2014-06-01

    Full Text Available Cancer control is a tremendous challenge not only for the ill patient and physicians, but also for the whole health care system. For the first time, during the European Conference of Oncology Pharmacists, the highest standards of pharmaceutical care were proposed for cancer patients. Undoubtedly, the lifestyle and prophylaxis which would enable the detection of cancer at an early stage exert an effect on the development of the disease. Cytostatics show toxic, mutagenic, oncogenic and immunosuppressive effects; therefore, their preparation should be handled by the Central Cytotoxic Drugs Department, because the majority of the drugs prepared belong to Register A. Drugs are manufactured in accordance with GMP principles. All-Polish Standards adopted by the Polish Pharmaceutical Association delineate the direction to be developed by every hospital with respect to its own procedures and instructions. The Master of Pharmacy is responsible for the preparation of cytotoxic drugs. At one bench should work an operator and an assistant. The recommended working time should not exceed 2 h without break, and 5 h daily. The person who collects cytotoxic drugs from the Central Department should use a legible sign and a stamp including the hour and date of collection. While manufacturing cytostatics for patients in daily doses it is recommended to use concentrates in the form of solutions rather than lyophilised powders, which results in the shortening of the stage of production of the drug and reduces the possibility of forming aerosols; in the case of closed infusion systems (containers for infusion liquids which are used for the production of daily doses, the cabinet should be equipped in two tight docks for dispensing. Needleless connection of the LUER-LOCK type – a recommendation of the ISOPP – guarantees a tight connection with the drug transfer port even in the case of an increase in pressure during the manufacture of drugs. To a certain extent

  10. Highly Sensitive Cadmium Concentration Sensor Using Long Period Grating

    Directory of Open Access Journals (Sweden)

    A. S. Lalasangi

    2011-08-01

    Full Text Available In this paper we have proposed a simple and effective Long Period Grating chemical sensor for detecting the traces of Cadmium (Cd++ in drinking water at ppm level. Long Period gratings (LPG were fabricated by point-by-point technique with CO2 laser. We have characterized the LPG concentration sensor sensitivity for different solutions of Cd concentrations varying from 0.01 ppm to 0.04 ppm by injecting white Light source and observed transmitted spectra using Optical Spectrum Analyzer (OSA. Proper reagents have been used in the solutions for detection of the Cd species. The overall shift in wavelength is 10 nm when surrounding medium gradually changed from water to 0.04 ppm of cadmium concentrations. A comparative study has been done using sophisticated spectroscopic atomic absorption spectrometer (AAS and Inductively Coupled Plasma (ICP instruments. The spectral sensitivity enhancement was done by modifying grating surface with gold nanoparticles.

  11. Carbon dioxide concentrations are very high in developing oilseeds.

    Science.gov (United States)

    Goffman, Fernando D; Ruckle, Mike; Ohlrogge, John; Shachar-Hill, Yair

    2004-09-01

    A new method has been developed to rapidly determine the total inorganic carbon concentration (gaseous [CO2] + aqueous [CO(2)] + [HCO3-] + [CO3(2)-]) in developing seeds. Seeds are rapidly dissected and homogenized in 1 N HCl in gas-tight vials. The headspace gas is then analyzed by infrared gas analysis. Developing rapeseed (Brassica napus L.) and soybean [Glycine max (L.) Merr.] seeds were analyzed and found to have up to 40 and 12 mM total inorganic carbon, respectively. These concentrations are ca. 600-2000-fold higher than in ambient air or values reported for leaves. Carbon dioxide concentrations in rapeseed peaked during the stage of maximum oil synthesis and declined as seeds matured. The consequences for seed metabolism, physiology and carbon economy are discussed.

  12. The obtaining a high-grade gadolinium concentrate

    International Nuclear Information System (INIS)

    Soltysiak, I.; Ozga, W.

    1982-01-01

    Gadolinium concentrates obtained by the fractional precipitation of lanthanon-potassium double chromates were separated by ion exchange with 0,4 M lactic acid solution in the presence of 0,1 M ammonium nitrate at pH of the medium 2,95-3,4. It was found out, that using the fractional precipitation of lanthanon-potassium double chromates (as the fast and cheap method that does not need special equipment) together with ion exchange separation with lactic acid solution as the eluent gave a highgrade gadolinium concentrate in a quick and economical way. (author)

  13. 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.

  14. Toward the establishment of standardized in vitro tests for lipid-based formulations. 2. The effect of bile salt concentration and drug loading on the performance of type I, II, IIIA, IIIB, and IV formulations during in vitro digestion.

    Science.gov (United States)

    Williams, Hywel D; Anby, Mette U; Sassene, Philip; Kleberg, Karen; Bakala-N'Goma, Jean-Claude; Calderone, Marilyn; Jannin, Vincent; Igonin, Annabel; Partheil, Anette; Marchaud, Delphine; Jule, Eduardo; Vertommen, Jan; Maio, Mario; Blundell, Ross; Benameur, Hassan; Carrière, Frédéric; Müllertz, Anette; Pouton, Colin W; Porter, Christopher J H

    2012-11-05

    The LFCS Consortium was established to develop standardized in vitro tests for lipid-based formulations (LBFs) and to examine the utility of these tests to probe the fundamental mechanisms that underlie LBF performance. In this publication, the impact of bile salt (sodium taurodeoxycholate, NaTDC) concentration and drug loading on the ability of a range of representative LBFs to generate and sustain drug solubilization and supersaturation during in vitro digestion testing has been explored and a common driver of the potential for drug precipitation identified. Danazol was used as a model poorly water-soluble drug throughout. In general, increasing NaTDC concentrations increased the digestion of the most lipophilic LBFs and promoted lipid (and drug) trafficking from poorly dispersed oil phases to the aqueous colloidal phase (AP(DIGEST)). High NaTDC concentrations showed some capacity to reduce drug precipitation, although, at NaTDC concentrations ≥3 mM, NaTDC effects on either digestion or drug solubilization were modest. In contrast, increasing drug load had a marked impact on drug solubilization. For LBFs containing long-chain lipids, drug precipitation was limited even at drug loads approaching saturation in the formulation and concentrations of solubilized drug in AP(DIGEST) increased with increased drug load. For LBFs containing medium-chain lipids, however, significant precipitation was evident, especially at higher drug loads. Across all formulations a remarkably consistent trend emerged such that the likelihood of precipitation was almost entirely dependent on the maximum supersaturation ratio (SR(M)) attained on initiation of digestion. SR(M) defines the supersaturation "pressure" in the system and is calculated from the maximum attainable concentration in the AP(DIGEST) (assuming zero precipitation), divided by the solubility of the drug in the colloidal phases formed post digestion. For LBFs where phase separation of oil phases did not occur, a

  15. 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

  16. Stability of Human Telomere Quadruplexes at High DNA Concentrations

    Czech Academy of Sciences Publication Activity Database

    Kejnovská, Iva; Vorlíčková, Michaela; Brázdová, Marie; Sagi, J.

    2014-01-01

    Roč. 101, č. 4 (2014), s. 428-438 ISSN 0006-3525 R&D Projects: GA ČR(CZ) GAP205/12/0466 Institutional support: RVO:68081707 Keywords : quadruplex * DNA concentration * folding topology Subject RIV: BO - Biophysics Impact factor: 2.385, year: 2014

  17. High concentrations of natural rubber latex allergens in gloves used ...

    African Journals Online (AJOL)

    Introduction. Gloves made of natural rubber latex (NRL) are commonly used by healthcare workers because of their good qualities. However, allergic reactions to latex allergens are still commonly reported. Objective. To measure the concentrations of Hev b 1, Hev b 3, Hev b 5 and Hev b 6.02 allergens in gloves used by a ...

  18. Mass Spectrometry to Determine Intracellular Concentrations of Antiretroviral Drugs: From chemistry to clinical application

    NARCIS (Netherlands)

    J.J.A. van Kampen (Jeroen)

    2009-01-01

    textabstractAround 1995 – 1996, treatment options for patients infected with the human immunodefiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS) 1, 2, improved dramatically. Therapy with a combination of several classes of antiretroviral drugs resulted in a

  19. High concentrations of pepsin in bronchoalveolar lavage fluid from children with cystic fibrosis are associated with high interleukin-8 concentrations.

    LENUS (Irish Health Repository)

    McNally, P

    2012-02-01

    BACKGROUND: Gastro-oesophageal reflux is common in children with cystic fibrosis (CF) and is thought to be associated with pulmonary aspiration of gastric contents. The measurement of pepsin in bronchoalveolar lavage (BAL) fluid has recently been suggested to be a reliable indicator of aspiration. The prevalence of pulmonary aspiration in a group of children with CF was assessed and its association with lung inflammation investigated. METHODS: This was a cross-sectional case-control study. BAL fluid was collected from individuals with CF (n=31) and healthy controls (n=7). Interleukin-8 (IL-8), pepsin, neutrophil numbers and neutrophil elastase activity levels were measured in all samples. Clinical, microbiological and lung function data were collected from medical notes. RESULTS: The pepsin concentration in BAL fluid was higher in the CF group than in controls (mean (SD) 24.4 (27.4) ng\\/ml vs 4.3 (4.0) ng\\/ml, p=0.03). Those with CF who had raised pepsin concentrations had higher levels of IL-8 in the BAL fluid than those with a concentration comparable to controls (3.7 (2.7) ng\\/ml vs 1.4 (0.9) ng\\/ml, p=0.004). Within the CF group there was a moderate positive correlation between pepsin concentration and IL-8 in BAL fluid (r=0.48, p=0.04). There was no association between BAL fluid pepsin concentrations and age, sex, body mass index z score, forced expiratory volume in 1 s or Pseudomonas aeruginosa colonisation status. CONCLUSIONS: Many children with CF have increased levels of pepsin in the BAL fluid compared with normal controls. Increased pepsin levels were associated with higher IL-8 concentrations in BAL fluid. These data suggest that aspiration of gastric contents occurs in a subset of patients with CF and is associated with more pronounced lung inflammation.

  20. Mechanisms of astrocytic K(+) clearance and swelling under high extracellular K(+) concentrations.

    Science.gov (United States)

    Murakami, Shingo; Kurachi, Yoshihisa

    2016-03-01

    In response to the elevation of extracellular K(+) concentration ([K(+)]out), astrocytes clear excessive K(+) to maintain conditions necessary for neural activity. K(+) clearance in astrocytes occurs via two processes: K(+) uptake and K(+) spatial buffering. High [K(+)]out also induces swelling in astrocytes, leading to edema and cell death in the brain. Despite the importance of astrocytic K(+) clearance and swelling, the underlying mechanisms remain unclear. Here, we report results from a simulation analysis of astrocytic K(+) clearance and swelling. Astrocyte models were constructed by incorporating various mechanisms such as intra/extracellular ion concentrations of Na(+), K(+), and Cl(-), cell volume, and models of Na,K-ATPase, Na-K-Cl cotransporter (NKCC), K-Cl cotransporter, inwardly-rectifying K(+) (KIR) channel, passive Cl(-) current, and aquaporin channel. The simulated response of astrocyte models under the uniform distribution of high [K(+)]out revealed significant contributions of NKCC and Na,K-ATPase to increases of intracellular K(+) and Cl(-) concentrations, and swelling. Moreover, we found that, under the non-uniform distribution of high [K(+)]out, KIR channels localized at synaptic clefts absorbed excess K(+) by depolarizing the equivalent potential of K(+) (E K) above membrane potential, while K(+) released through perivascular KIR channels was enhanced by hyperpolarizing E K and depolarizing membrane potential. Further analysis of simulated drug effects revealed that astrocyte swelling was modulated by blocking each of the ion channels and transporters. Our simulation analysis revealed controversial mechanisms of astrocytic K(+) clearance and swelling resulting from complex interactions among ion channels and transporters.

  1. 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…

  2. High pressure inertial focusing for separating and concentrating bacteria at high throughput

    Science.gov (United States)

    Cruz, J.; Hooshmand Zadeh, S.; Graells, T.; Andersson, M.; Malmström, J.; Wu, Z. G.; Hjort, K.

    2017-08-01

    Inertial focusing is a promising microfluidic technology for concentration and separation of particles by size. However, there is a strong correlation of increased pressure with decreased particle size. Theory and experimental results for larger particles were used to scale down the phenomenon and find the conditions that focus 1 µm particles. High pressure experiments in robust glass chips were used to demonstrate the alignment. We show how the technique works for 1 µm spherical polystyrene particles and for Escherichia coli, not being harmful for the bacteria at 50 µl min-1. The potential to focus bacteria, simplicity of use and high throughput make this technology interesting for healthcare applications, where concentration and purification of a sample may be required as an initial step.

  3. 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.

  4. High-performance flat-panel solar thermoelectric generators with high thermal concentration

    Science.gov (United States)

    Kraemer, Daniel; Poudel, Bed; Feng, Hsien-Ping; Caylor, J. Christopher; Yu, Bo; Yan, Xiao; Ma, Yi; Wang, Xiaowei; Wang, Dezhi; Muto, Andrew; McEnaney, Kenneth; Chiesa, Matteo; Ren, Zhifeng; Chen, Gang

    2011-07-01

    The conversion of sunlight into electricity has been dominated by photovoltaic and solar thermal power generation. Photovoltaic cells are deployed widely, mostly as flat panels, whereas solar thermal electricity generation relying on optical concentrators and mechanical heat engines is only seen in large-scale power plants. Here we demonstrate a promising flat-panel solar thermal to electric power conversion technology based on the Seebeck effect and high thermal concentration, thus enabling wider applications. The developed solar thermoelectric generators (STEGs) achieved a peak efficiency of 4.6% under AM1.5G (1 kW m-2) conditions. The efficiency is 7-8 times higher than the previously reported best value for a flat-panel STEG, and is enabled by the use of high-performance nanostructured thermoelectric materials and spectrally-selective solar absorbers in an innovative design that exploits high thermal concentration in an evacuated environment. Our work opens up a promising new approach which has the potential to achieve cost-effective conversion of solar energy into electricity.

  5. High-performance flat-panel solar thermoelectric generators with high thermal concentration.

    Science.gov (United States)

    Kraemer, Daniel; Poudel, Bed; Feng, Hsien-Ping; Caylor, J Christopher; Yu, Bo; Yan, Xiao; Ma, Yi; Wang, Xiaowei; Wang, Dezhi; Muto, Andrew; McEnaney, Kenneth; Chiesa, Matteo; Ren, Zhifeng; Chen, Gang

    2011-05-01

    The conversion of sunlight into electricity has been dominated by photovoltaic and solar thermal power generation. Photovoltaic cells are deployed widely, mostly as flat panels, whereas solar thermal electricity generation relying on optical concentrators and mechanical heat engines is only seen in large-scale power plants. Here we demonstrate a promising flat-panel solar thermal to electric power conversion technology based on the Seebeck effect and high thermal concentration, thus enabling wider applications. The developed solar thermoelectric generators (STEGs) achieved a peak efficiency of 4.6% under AM1.5G (1 kW m(-2)) conditions. The efficiency is 7-8 times higher than the previously reported best value for a flat-panel STEG, and is enabled by the use of high-performance nanostructured thermoelectric materials and spectrally-selective solar absorbers in an innovative design that exploits high thermal concentration in an evacuated environment. Our work opens up a promising new approach which has the potential to achieve cost-effective conversion of solar energy into electricity. © 2011 Macmillan Publishers Limited. All rights reserved

  6. Cost-effectiveness of routine measuring of serum drug concentrations and anti-drug antibodies in treatment of rheumatoid arthritis patients with TNF-α blockers

    Directory of Open Access Journals (Sweden)

    Laine J

    2016-04-01

    Full Text Available Juha Laine,1 T Sakari Jokiranta,2,3 Kari K Eklund,4,5 Merja Väkeväinen,1 Kari Puolakka6 1Pfizer Oy, Helsinki, 2United Medix Laboratories Ltd, Espoo, 3Research Programs Unit, Immunobiology, 4Department of Rheumatology, University of Helsinki, 5Helsinki University Central Hospital, Helsinki, 6Department of Medicine, South Karelia, Finland Abstract: Monitoring of anti-drug antibodies (ADAbs or serum concentrations of biologicals in treatment of rheumatoid arthritis could provide an explanation for a loss of efficacy and help in the choice of subsequent medication. Current clinical practices do not generally include such monitoring of tumor necrosis factor (TNF-α blockers on a routine basis. The main aims of this study were to estimate the probabilities of optimal and nonoptimal treatment decisions if infliximab or adalimumab drug trough level (DL and ADAbs are tested or not in rheumatoid arthritis, and to model cost-effectiveness of performing such monitoring on a routine basis. Data on DLs and ADAbs concentrations were obtained in Finland from clinically requested monitoring analyses of 486 and 1,137 samples from patients on adalimumab and infliximab, respectively. DL was within the target range in 42% of samples from adalimumab- and 50.4% of infliximab-treated patients. ADAbs were detected in approximately 20% and 13.5% of samples from adalimumab- and infliximab-treated patients, respectively. ADAbs were found in 52.3% and 41.3% of those with low adalimumab or infliximab DLs, respectively. The monitoring data were incorporated into probabilities for making the optimal treatment decision. Economic impact of clinical decision-making was modeled in a short-term (3–6 months scenario with 100 hypothetical patients. In the model, the combined measurement of DLs and ADAbs was cost-saving compared to the nontesting scenario when the monitoring results affected the treatment decision in at least 2–5 of 100 patients, a proportion which is easily

  7. Mangiferin binding to serum albumin is non-saturable and induces conformational changes at high concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Freitas, P.G.; Barbosa, A.F. [Biochemistry Laboratory, Institute of Exact Sciences, Federal University of Alfenas, Unifal-MG, R. Gabriel Monteiro da Silva, 700, 37130-000 Alfenas, MG (Brazil); Saraiva, L.A. [Phytochemistry and Medicinal Chemistry Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Camps, I. [Physics Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Silveira, N.J.F. da [Bioinformatics Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Veloso, M.P. [Phytochemistry and Medicinal Chemistry Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Santos, M.H., E-mail: poliany.santos@gmail.com [Phytochemistry and Medicinal Chemistry Laboratory, Institute of Exact Sciences, Unifal-MG (Brazil); Schneedorf, J.M., E-mail: zemasfs@gmail.com [Biochemistry Laboratory, Institute of Exact Sciences, Federal University of Alfenas, Unifal-MG, R. Gabriel Monteiro da Silva, 700, 37130-000 Alfenas, MG (Brazil)

    2012-11-15

    The binding interaction between mangiferin (MGF), which a natural xanthone isolated from mangoes, and bovine serum albumin (BSA) was studied with absorbance and fluorescence spectroscopy, cyclic voltammetry and molecular modeling. The data were analyzed to assess the binding mechanism, effect of pH and ionic strength, conformational changes in the protein and electrical charge transfer involved. The MGF-BSA complex exhibited positive cooperativity with a 1:1 stoichiometry (K{sub d}=0.38 mmol L{sup -1}) for the first binding site and a non-saturable binding at high ligand concentrations. Furthermore, the data also suggest an increase in drug bioavailability in the acidic region and relatively low ionic strength values, which are close to physiological levels. The data suggest a specific electrostatic interaction together with hydrophobic effects and H-bonding displayed in MGF binding to the BSA IIA subdomain. Synchronous fluorescence spectra indicate that there are conformational changes in the polypeptide backbone upon ligand binding. Cyclic voltammetry indicates that there is an irreversible charge transfer between MGF and BSA that is modulated by diffusion on the electrode surface, where two electrons are transferred. These results can help the knowledge of the pharmacokinetic activities of natural or chemical xanthone-based drugs. - Highlights: Black-Right-Pointing-Pointer The MGF-BSA complex exhibited positive cooperativity beyond 1:1 stoichiometry. Black-Right-Pointing-Pointer The interaction of MGF with BSA is non-saturable at higher ligand concentration. Black-Right-Pointing-Pointer The binding was accomplished by H-bonding, hydrophobic and electrostatic forces. Black-Right-Pointing-Pointer The apparent binding constant for MGF-BSA was 0.38 mmol L{sup -1}. Black-Right-Pointing-Pointer MGF binds electrostatically to BSA, different from a hydrophobic interaction to HSA.

  8. 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…

  9. Nonsmoker Exposure to Secondhand Cannabis Smoke. III. Oral Fluid and Blood Drug Concentrations and Corresponding Subjective Effects.

    Science.gov (United States)

    Cone, Edward J; Bigelow, George E; Herrmann, Evan S; Mitchell, John M; LoDico, Charles; Flegel, Ronald; Vandrey, Ryan

    2015-09-01

    The increasing use of highly potent strains of cannabis prompted this new evaluation of human toxicology and subjective effects following passive exposure to cannabis smoke. The study was designed to produce extreme cannabis smoke exposure conditions tolerable to drug-free nonsmokers. Six experienced cannabis users smoked cannabis cigarettes [5.3% Δ(9)-tetrahydrocannabinol (THC) in Session 1 and 11.3% THC in Sessions 2 and 3] in a closed chamber. Six nonsmokers were seated alternately with smokers during exposure sessions of 1 h duration. Sessions 1 and 2 were conducted with no ventilation and ventilation was employed in Session 3. Oral fluid, whole blood and subjective effect measures were obtained before and at multiple time points after each session. Oral fluid was analyzed by ELISA (4 ng/mL cutoff concentration) and by LC-MS-MS (limit of quantitation) for THC (1 ng/mL) and total THCCOOH (0.02 ng/mL). Blood was analyzed by LC-MS-MS (0.5 ng/mL) for THC, 11-OH-THC and free THCCOOH. Positive tests for THC in oral fluid and blood were obtained for nonsmokers up to 3 h following exposure. Ratings of subjective effects correlated with the degree of exposure. Subjective effect measures and amounts of THC absorbed by nonsmokers (relative to smokers) indicated that extreme secondhand cannabis smoke exposure mimicked, though to a lesser extent, active cannabis smoking. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. Probe for intracellular concentrations of drugs: delayed fluorescence from acridine orange

    International Nuclear Information System (INIS)

    Wardman, P.; Dennis, M.F.; White, J.

    1989-01-01

    The aim of this work is to develop fluorescent probes that will indicate effective concentrations of therapeutic agents, or endogenous protectors, at important cellular sites. Acridine orange associates with nucleic acids and emits a 'delayed' fluorescence signal. This signal is quenched by oxidants such as oxygen, nitroaryl radiosensitizers, adriamycin and mitomycin-c, and reductants such as thiols, ascorbate and other radioprotectors. The quenching of the acridine orange delayed fluorescence reflects the effective concentration of these therapeutically-important oxidants and reductants near DNA. The relative concentration of basic radiosensitizers such as pimonidazole (Ro 03-8799) near the DNA is greater than that of misonidazole. Thiols quench the delayed fluorescence signal according to the degree of ionization of the thiol function; this may model the reactivity of thiols with guanine radical sites in DNA. Ascorbate and aminopyrine do not quench the delayed fluorescence from cells stained with acridine orange as these compounds are taken up by cells very inefficiently

  11. Experimental Determination of Drug Diffusion Coefficients in Unstirred Aqueous Environments by Temporally Resolved Concentration Measurements

    DEFF Research Database (Denmark)

    Di Cagno, Massimiliano Pio; Clarelli, Fabrizio; Vabenø, Jon

    2018-01-01

    or the need for dedicated instrumentation. In this work, a simple but reliable method based on time resolved concentration measurements by UV-visible spectroscopy in an unstirred aqueous environment was developed. This method is based on spectroscopic measurement of the variation of the local concentration...... characteristics (i.e. ionic strength and presence of complexing agents) on the diffusivity. The method can be employed in any research laboratory equipped with a standard UV-visible spectrophotometer, and could become a useful and straightforward tool in order to characterize diffusion coefficients...

  12. Spontaneous deswelling of pNIPAM microgels at high concentrations

    Science.gov (United States)

    Gasser, Urs; Scotti, Andrea; Herman, Emily S.; Pelaez-Fernandez, Miguel; Han, Jun; Menzel, Andreas; Lyon, L. Andrew; Fernandez-Nieves, Alberto

    Polydisperse suspensions of pNIPAM microgel particles show a unique, spontaneous particle deswelling behavior. Beyond a critical concentration, the largest microgels deswell and thereby reduce the polydispersity of the suspension. We have recently unraveled the mechanism of this spontaneous, selective deswelling. pNIPAM microgels carry charged sulfate groups originating from the ammonium persulfate starter used in particle synthesis. Most of the ammonium counterions are trapped close to the microgel surface, but a fraction of them escapes the electrostatic attraction and contributes to the osmotic pressure of the suspension. The counterion clouds of neighboring particles progressively overlap with increasing volume fraction, leading to an increase of free counterions and the osmotic pressure outside but not inside the microgel particles. We find particles to deswell when the resulting osmotic pressure difference between the inside and the outside becomes larger their bulk modulus. For pNIPAM microgels synthesized with the same protocol, the largest particles are the softest and deswell first.

  13. Polylysine as a vehicle for extracellular matrix-targeted local drug delivery, providing high accumulation and long-term retention within the vascular wall

    NARCIS (Netherlands)

    Sakharov, D.V.; Jie, A.F.H.; Bekkers, M.E.A.; Emeis, J.J.; Rijken, D.C.

    2001-01-01

    We present the first steps in the elaboration of an approach of extracellular matrix-targeted local drug delivery (ECM-LDD), designed to provide a high concentration, ubiquitous distribution, and long-term retention of a drug within the vessel wall after local intravascular delivery. The approach is

  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. Differential mechanism of Escherichia coli Inactivation by (+)-limonene as a function of cell physiological state and drug's concentration.

    Science.gov (United States)

    Chueca, Beatriz; Pagán, Rafael; García-Gonzalo, Diego

    2014-01-01

    (+)-limonene is a lipophilic antimicrobial compound, extracted from citrus fruits' essential oils, that is used as a flavouring agent and organic solvent by the food industry. A recent study has proposed a common and controversial mechanism of cell death for bactericidal antibiotics, in which hydroxyl radicals ultimately inactivated cells. Our objective was to determine whether the mechanism of Escherichia coli MG1655 inactivation by (+)-limonene follows that of bactericidal antibiotics. A treatment with 2,000 μL/L (+)-limonene inactivated 4 log10 cycles of exponentially growing E. coli cells in 3 hours. On one hand, an increase of cell survival in the ΔacnB mutant (deficient in a TCA cycle enzyme), or in the presence of 2,2'-dipyridyl (inhibitor of Fenton reaction by iron chelation), thiourea, or cysteamine (hydroxyl radical scavengers) was observed. Moreover, the ΔrecA mutant (deficient in an enzyme involved in SOS response to DNA damage) was more sensitive to (+)-limonene. Thus, this indirect evidence indicates that the mechanism of exponentially growing E. coli cells inactivation by 2,000 μL/L (+)-limonene is due to the TCA cycle and Fenton-mediated hydroxyl radical formation that caused oxidative DNA damage, as observed for bactericidal drugs. However, several differences have been observed between the proposed mechanism for bactericidal drugs and for (+)-limonene. In this regard, our results demonstrated that E. coli inactivation was influenced by its physiological state and the drug's concentration: experiments with stationary-phase cells or 4,000 μL/L (+)-limonene uncovered a different mechanism of cell death, likely unrelated to hydroxyl radicals. Our research has also shown that drug's concentration is an important factor influencing the mechanism of bacterial inactivation by antibiotics, such as kanamycin. These results might help in improving and spreading the use of (+)-limonene as an antimicrobial compound, and in clarifying the controversy about

  17. 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

  18. 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

  19. 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

  20. High Concentration Protein Ultrafiltration: a Comparative Fouling Assessment

    Science.gov (United States)

    Lim, Y. P.; Mohammad, A. W.

    2018-05-01

    In this paper, the predominant fouling mechanism via pH manipulation in gelatin ultrafiltration (UF) at constant operating pressure was studied. Two 30 kDa molecular weight cut off (MWCO) UF membranes with different hydrophilic/hydrophobic properties were tested at solution pH near gelatin isoelectric point (IEP), pH below and above gelatin’s IEP. The resistance-in-series model was used to determine quantitatively the contribution of each filtration resistance occurred during gelatin UF. The governing fouling mechanisms were investigated using classical blocking laws. The results demonstrated that concentration polarization remain as dominant fouling resistance in gelatin UF, but exceptional case was observed at pH away from gelatin’s IEP, showing that combined reversible and irreversible fouling resistances contributed around 57% and 37%, respectively to the overall fouling resistances. Under all experimental condition tested, permeate flux decline was accurately predicted by all the models studied. Fouling profile was fitted well with “Standard Blocking”, “Intermediate Blocking” and “Cake Filtration” model for regenerated cellulose acetate (RCA) membrane and “Cake Filtration” model for polyethersulphone (PES) membrane.

  1. Adaptive sensor-based ultra-high accuracy solar concentrator tracker

    Science.gov (United States)

    Brinkley, Jordyn; Hassanzadeh, Ali

    2017-09-01

    Conventional solar trackers use information of the sun's position, either by direct sensing or by GPS. Our method uses the shading of the receiver. This, coupled with nonimaging optics design allows us to achieve ultra-high concentration. Incorporating a sensor based shadow tracking method with a two stage concentration solar hybrid parabolic trough allows the system to maintain high concentration with acute accuracy.

  2. 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

  3. 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.

  4. Bromfenac ophthalmic solution 0.09 %: human aqueous humor concentration detected by high-performance liquid chromatography.

    Science.gov (United States)

    Macrì, Angelo; Vagge, Aldo; Salis, Annalisa; Fucile, Carmen; Marini, Valeria; Martelli, Antonietta; Giuffrida, Sebastiano; Iester, Michele; Damonte, Gianluca; Mattioli, Francesca

    2017-04-01

    The purpose of this study was to evaluate the aqueous humor concentrations of bromfenac ophthalmic solution 0.09 % in patients undergoing phacoemulsification. Patients requiring cataract extraction received one drop (50 µL) of bromfenac 0.09 % solution in the eye to be operated, before bedtime the day before surgery or the morning of the surgery. The last administration was recorded. At the time of paracentesis, an aqueous humor sample was collected with a 30-gauge needle attached to a TB syringe and was later analyzed by high-performance liquid chromatography for drug concentration. 188 treated volunteers and 48 control, untreated, subjects were included in the study. The mean aqueous concentration of bromfenac in the treated group was 37.60 ± 68.86 and 0 nM (nmol/L) in the control group (p < 0.0001). Correlation coefficient in bromfenac group between time elapsed from instillation and drug concentration was -0.16 (p not significant). Bromfenac showed properties of good penetration and stable concentration in aqueous humor up to about 12 h after instillation.

  5. Deep Sea Memory of High Atmospheric CO2 Concentration

    Science.gov (United States)

    Mathesius, Sabine; Hofmann, Matthias; Caldeira, Ken; Schellnhuber, Hans Joachim

    2015-04-01

    Carbon dioxide removal (CDR) from the atmosphere has been proposed as a powerful measure to mitigate global warming and ocean acidification. Planetary-scale interventions of that kind are often portrayed as "last-resort strategies", which need to weigh in if humankind keeps on enhancing the climate-system stock of CO2. Yet even if CDR could restore atmospheric CO2 to substantially lower concentrations, would it really qualify to undo the critical impacts of past emissions? In the study presented here, we employed an Earth System Model of Intermediate Complexity (EMIC) to investigate how CDR might erase the emissions legacy in the marine environment, focusing on pH, temperature and dissolved oxygen. Against a background of a world following the RCP8.5 emissions path ("business-as-usual") for centuries, we simulated the effects of two massive CDR interventions with CO2 extraction rates of 5 GtC yr-1 and 25 GtC yr-1, respectively, starting in 2250. We found that the 5 GtC yr-1 scheme would have only minor ameliorative influence on the oceans, even after several centuries of application. By way of contrast, the extreme 25 GtC yr-1 scheme eventually leads to tangible improvements. However, even with such an aggressive measure, past CO2 emissions leave a substantial legacy in the marine environment within the simulated period (i.e., until 2700). In summary, our study demonstrates that anthropogenic alterations of the oceans, caused by continued business-as-usual emissions, may not be reversed on a multi-centennial time scale by the most aspirational geoengineering measures. We also found that a transition from the RCP8.5 state to the state of a strong mitigation scenario (RCP2.6) is not possible, even under the assumption of extreme extraction rates (25 GtC yr-1). This is explicitly demonstrated by simulating additional scenarios, starting CDR already in 2150 and operating until the atmospheric CO2 concentration reaches 280 ppm and 180 ppm, respectively. The simulated

  6. High urinary phthalate concentration associated with delayed pubarche in girls

    DEFF Research Database (Denmark)

    Frederiksen, H; Sørensen, K; Mouritsen, A

    2012-01-01

    Phthalates are a group of chemicals present in numerous consumer products. They have anti-androgenic properties in experimental studies and are suspected to be involved in human male reproductive health problems. A few studies have shown associations between phthalate exposure and changes...... and controls. We demonstrated that delayed pubarche, but not thelarche, was associated with high phthalate excretion in urine samples from 725 healthy school girls, which may suggest anti-androgenic actions of phthalates in our study group of girls....

  7. High plasma uric acid concentration: causes and consequences

    Directory of Open Access Journals (Sweden)

    de Oliveira Erick

    2012-04-01

    Full Text Available Abstract High plasma uric acid (UA is a precipitating factor for gout and renal calculi as well as a strong risk factor for Metabolic Syndrome and cardiovascular disease. The main causes for higher plasma UA are either lower excretion, higher synthesis or both. Higher waist circumference and the BMI are associated with higher insulin resistance and leptin production, and both reduce uric acid excretion. The synthesis of fatty acids (tryglicerides in the liver is associated with the de novo synthesis of purine, accelerating UA production. The role played by diet on hyperuricemia has not yet been fully clarified, but high intake of fructose-rich industrialized food and high alcohol intake (particularly beer seem to influence uricemia. It is not known whether UA would be a causal factor or an antioxidant protective response. Most authors do not consider the UA as a risk factor, but presenting antioxidant function. UA contributes to > 50% of the antioxidant capacity of the blood. There is still no consensus if UA is a protective or a risk factor, however, it seems that acute elevation is a protective factor, whereas chronic elevation a risk for disease.

  8. Interdependence of initial cell density, drug concentration and exposure time revealed by real-time impedance spectroscopic cytotoxicity assay

    DEFF Research Database (Denmark)

    Caviglia, Claudia; Zor, Kinga; Canepa, Silvia

    2015-01-01

    We investigated the combined effect of the initial cell density (12 500, 35 000, 75 000, and 100 000 cells cm−2) and concentration of the anti-cancer drug doxorubicin on HeLa cells by performing timedependent cytotoxicity assays using real-time electrochemical impedance spectroscopy. A correlation...... between the rate of cell death and the initial cell seeding density was found at 2.5 μM doxorubicin concentration, whereas this was not observed at 5 or 100 μM. By sensing the changes in the cell–substrate interaction using impedance spectroscopy under static conditions, the onset of cytotoxicity...... was observed 5 h earlier than when using a standard colorimetric end-point assay (MTS) which measures changes in the mitochondrial metabolism. Furthermore, with the MTS assay no cytotoxicity was observed after 15 h of incubation with 2.5 μM doxorubicin, whereas the impedance showed at this time point cell...

  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. Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.

    Science.gov (United States)

    Vainionpää, Mari H; Raekallio, Marja R; Pakkanen, Soile A E; Ranta-Panula, Ville; Rinne, Valtteri M; Scheinin, Mika; Vainio, Outi M

    2013-05-01

    To investigate plasma drug concentrations and the effect of MK-467 (L-659'066) on sedation, heart rate and gut motility in horses sedated with intravenous (IV) detomidine. Experimental randomized blinded crossover study. Six healthy horses. Detomidine (10 μg kg(-1) IV) was administered alone (DET) and in combination with MK-467 (250 μg kg(-1) IV; DET + MK). The level of sedation and intestinal sounds were scored. Heart rate (HR) and central venous pressure (CVP) were measured. Blood was collected to determine plasma drug concentrations. Repeated measures anova was used for HR, CVP and intestinal sounds, and the Student's t-test for pairwise comparisons between treatments for the area under the time-sedation curve (AUCsed ) and pharmacokinetic parameters. Significance was set at p Detomidine-induced intestinal hypomotility was prevented by MK-467. AUCsed was significantly higher with DET than DET + MK, but maximal sedations scores did not differ significantly between treatments. MK-467 lowered the AUC of the plasma concentration of detomidine, and increased its volume of distribution and clearance. MK-467 prevented detomidine induced bradycardia and intestinal hypomotility. MK-467 did not affect the clinical quality of detomidine-induced sedation, but the duration of the effect was reduced, which may have been caused by the effects of MK-467 on the plasma concentration of detomidine. MK-467 may be useful clinically in the prevention of certain peripheral side effects of detomidine in horses. © 2013 The Authors. Veterinary Anaesthesia and Analgesia © 2013 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  11. Intraoperative radiotherapy in combination with misonidazole. In special reference to the drug concentration in tumors and normal tissues and to the initial effect of the treatment

    Energy Technology Data Exchange (ETDEWEB)

    Takahashi, Masaji; Ono, Kouji; Hamanaka, Daizaburo; Dodo, Yoshihiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Faculty of Medicine

    1983-03-01

    A hypoxic cell radiosensitizer, misonidazole, was applied to 28 patients with carcinoma who received intraoperative radiotherapy. A single dose of 2-3g/m/sup 2/ of the drug was given orally to each patient three hours prior to the start of general anesthesia. The levels of misonidazole and its metabolite, desmethylmisonidazole, in blood, tumors and normal tissues taken from excised materials were measured by a high performance liquid chromatography. The results showed that the concentration levels of misonidazole and desmethylmisonidazole in blood correlated neither to oral doses of 2-3g/m/sup 2/ nor to the function of time after drug ingestion until eight hours. The mean value of blood levels was 77.1 +- 10.9..mu..g/ml. A wide range of 10-96% of the blood level was found in tumors. High levels were observed in gastric cancer and brain tumor (glioblastoma) but not in colorectal cancer and osteosarcoma. It was, however, likely that the concentrations in tumors depended on tumor sizes and/or necrotic areas rather than histologic types and/or sites of tumors. It was also noted that the concentration in normal tissues ranged widely from 11 to 87% of the blood level. Higher concentrations showing more than 75% were found in the ulnar nerve, the stomach and the skin. However, 3 of 4 materials for the stomach and 2 of 3 materials for the skin showed low levels of less than 30% and less than 22% respectively. In 27 of 28 cases different doses of 28-50 Gy with different energies of electrons were delivered intraoperatively. It is impossible so far to derive conclusive results of this study, really because of the short period of observation following the treatment.

  12. 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.

  13. 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…

  14. 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.

  15. 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)

  16. 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

  17. High-order optical nonlinearities in nanocomposite films dispersed with semiconductor quantum dots at high concentrations

    International Nuclear Information System (INIS)

    Tomita, Yasuo; Matsushima, Shun-suke; Yamagami, Ryu-ichi; Jinzenji, Taka-aki; Sakuma, Shohei; Liu, Xiangming; Izuishi, Takuya; Shen, Qing

    2017-01-01

    We describe the nonlinear optical properties of inorganic-organic nanocomposite films in which semiconductor CdSe quantum dots as high as 6.8 vol.% are dispersed. Open/closed Z-scan measurements, degenerate multi-wave mixing and femtosecond pump-probe/transient grating measurements are conducted. It is shown that the observed fifth-order optical nonlinearity has the cascaded third-order contribution that becomes prominent at high concentrations of CdSe QDs. It is also shown that there are picosecond-scale intensity-dependent and nanosecond-scale intensity-independent decay components in absorptive and refractive nonlinearities. The former is caused by the Auger process, while the latter comes from the electron-hole recombination process. (paper)

  18. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

    Energy Technology Data Exchange (ETDEWEB)

    Ozolinš, Terence R.S., E-mail: ozolinst@queensu.ca [Department of Biomedical and Molecular Sciences, Program in Pharmacology and Toxicology, Queen’s University, Botterell Hall, Kingston, ON K7L 3N6 (Canada); Weston, Andrea D. [Currently at Applied Biotechnology/Lead Discovery, Bristol-Myers Squibb, 5 Research Pkwy Wallingford, CT 06492-1996 (United States); Perretta, Anthony [Currently at Pfizer Research and Development, Eastern Point Road, Groton, CT 06340 (United States); Thomson, Jason J. [Currently at Yale Stem Cell Center, Yale School of Medicine, PO Box 208073, New Haven, CT 06520-8073 (United States); Brown, Nigel A. [Division of Basic Medical Sciences, St. George’s University of London, UK SW17 0RE (United Kingdom)

    2015-11-15

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

  19. Dimethadione embryotoxicity in the rat is neither correlated with maternal systemic drug concentrations nor embryonic tissue levels

    International Nuclear Information System (INIS)

    Ozolinš, Terence R.S.; Weston, Andrea D.; Perretta, Anthony; Thomson, Jason J.; Brown, Nigel A.

    2015-01-01

    Pregnant rats treated with dimethadione (DMO), the N-demethylated metabolite of the anticonvulsant trimethadione, produce offspring having a 74% incidence of congenital heart defects (CHD); however, the incidence of CHD has high inter-litter variability (40–100%) that presents a challenge when studying the initiating events prior to the presentation of an abnormal phenotype. We hypothesized that the variability in CHD incidence was the result of differences in maternal systemic concentrations or embryonic tissue concentrations of DMO. To test this hypothesis, dams were administered 300 mg/kg DMO every 12 h from the evening of gestational day (GD) 8 until the morning of GD 11 (six total doses). Maternal serum levels of DMO were assessed on GD 11, 12, 13, 14, 15, 18 and 21. Embryonic tissue concentrations of DMO were assessed on GD 11, 12, 13 and 14. In a separate cohort of GD 12 embryos, DMO concentrations and parameters of growth and development were assessed to determine if tissue levels of DMO were correlated with these endpoints. Embryos were exposed directly to different concentrations of DMO with whole embryo culture (WEC) and their growth and development assessed. Key findings were that neither maternal systemic concentrations nor tissue concentrations of DMO identified embryos that were sensitive or resistant to DMO in vivo. Direct exposure of embryos to DMO via WEC also failed to show correlations between embryonic concentrations of DMO with developmental outcomes in vitro. We conclude that neither maternal serum nor embryonic tissue concentrations of DMO predict embryonic outcome. - Highlights: • Dimethadione (DMO) induces septation defects (VSD) in rat offspring. • Despite high rate of VSD defects inter-litter variability is 40–100%. • Maternal and embryonic concentrations of DMO were assessed. • Neither serum nor tissue levels of DMO were correlated with embryotoxicity.

  20. Emulsifier development for high-concentrated reverse emulsions

    Directory of Open Access Journals (Sweden)

    I.L. Kovalenko

    2016-05-01

    Full Text Available The reverse emulsions have found broad application in ore mining industry as matrixes of emulsion explosive substances and boring washing waters. The defining characteristic of reverse emulsions of industrial explosive substances is the high stability and immunity to crystallization. Aim: The aim of this work is to assess the mechanism of emulsifiers effect like SMO and some PIBSA-derivatives, that are most abundantly used in world practice, and also to develop an effective domestic emulsifier of reverse emulsions. Materials and methods: Using the semi-dynamic method with use of the reverse stalagmometer it was determined the decreasing in interfacial tension on “water / diesel fuel” border in the presence of 0.5 wt % sorbitan monooleate of various producers. Emulsions with use of the chosen emulsifiers using the dynamic mixer on the basis of monosolution of ammonium nitrate and diesel fuel have been produced. The emulsions have the following composition, wt %: ammonium nitrate – 76.8; water – 15.6; diesel fuel – 6.0; emulsifier – 1.6. Results: By the researches results of the interfacial tension “surfactant water / solution in diesel fuel”, the stability of emulsions using monosolution of ammonium nitrate and the IR spectrums of SMO of various producers it is established that presence in product of impurity of oleic acid, di- and trioleates leads to decreasing in interphase activity, increasing of emulsifier oil solubility and decreasing the resistance of emulsions to crystallization. On the basis of the spectral data analysis it is suggested about possibility of specific interaction on the mechanism of “spectral resonance” between emulsifiers of the PIBSA-MEA, LZX type and crystals nucleus of NH4NO3 ammonium nitrate in dispersed phase of emulsion. Amidation of vegetable oils by monoethanol amine is implemented at the reduced temperatures (90…100 °C. It was proved the availability mainly of fatty acids amides in product

  1. The Female Genital Tract Microbiome Is Associated With Vaginal Antiretroviral Drug Concentrations in Human Immunodeficiency Virus-Infected Women on Antiretroviral Therapy.

    Science.gov (United States)

    Donahue Carlson, Renee; Sheth, Anandi N; Read, Timothy D; Frisch, Michael B; Mehta, C Christina; Martin, Amy; Haaland, Richard E; Patel, Anar S; Pau, Chou-Pong; Kraft, Colleen S; Ofotokun, Igho

    2017-11-15

    The female genital tract (FGT) microbiome may affect vaginal pH and other factors that influence drug movement into the vagina. We examined the relationship between the microbiome and antiretroviral concentrations in the FGT. Over one menstrual cycle, 20 human immunodeficiency virus (HIV)-infected women virologically suppressed on tenofovir (TFV) disoproxil fumarate/emtricitabine and ritonavir-boosted atazanavir (ATV) underwent serial paired cervicovaginal and plasma sampling for antiretroviral concentrations using high-performance liquid chromatography-tandem mass spectrometry. Analysis of 16S ribosomal RNA gene sequencing of cervicovaginal lavage clustered each participant visit into a unique microbiome community type (mCT). Participants were predominantly African American (95%), with a median age of 38 years. Cervicovaginal lavage sequencing (n = 109) resulted in a low-diversity mCT dominated by Lactobacillus (n = 40), and intermediate-diversity (n = 28) and high-diversity (n = 41) mCTs with abundance of anaerobic taxa. In multivariable models, geometric mean FGT:plasma ratios varied significantly by mCT for all 3 drugs. For both ATV and TFV, FGT:plasma was significantly lower in participant visits with high- and low-diversity mCT groups (all P < .02). For emtricitabine, FGT:plasma was significantly lower in participant visits with low- vs intermediate-diversity mCT groups (P = .002). Certain FGT mCTs are associated with decreased FGT antiretroviral concentrations. These findings are relevant for optimizing antiretrovirals used for biomedical HIV prevention in women. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  2. Polymeric nanoparticles for increased oral bioavailability and rapid absorption using celecoxib as a model of a low-solubility, high-permeability drug.

    Science.gov (United States)

    Morgen, Michael; Bloom, Corey; Beyerinck, Ron; Bello, Akintunde; Song, Wei; Wilkinson, Karen; Steenwyk, Rick; Shamblin, Sheri

    2012-02-01

    To demonstrate drug/polymer nanoparticles can increase the rate and extent of oral absorption of a low-solubility, high-permeability drug. Amorphous drug/polymer nanoparticles containing celecoxib were prepared using ethyl cellulose and either sodium caseinate or bile salt. Nanoparticles were characterized using dynamic light scattering, transmission and scanning electron microscopy, and differential scanning calorimetry. Drug release and resuspension studies were performed using high-performance liquid chromatography. Pharmacokinetic studies were performed in dogs and humans. A physical model is presented describing the nanoparticle state of matter and release performance. Nanoparticles dosed orally in aqueous suspensions provided higher systemic exposure and faster attainment of peak plasma concentrations than commercial capsules, with median time to maximum drug concentration (Tmax) of 0.75 h in humans for nanoparticles vs. 3 h for commercial capsules. Nanoparticles released celecoxib rapidly and provided higher dissolved-drug concentrations than micronized crystalline drug. Nanoparticle suspensions are stable for several days and can be spray-dried to form dry powders that resuspend in water. Drug/polymer nanoparticles are well suited for providing rapid oral absorption and increased bioavailability of BCS Class II drugs.

  3. Soybean greatly reduces valproic acid plasma concentrations: A food–drug interaction study

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

    2014-01-01

    The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents. PMID:24618639

  4. Soybean greatly reduces valproic acid plasma concentrations: a food-drug interaction study.

    Science.gov (United States)

    Marahatta, Anu; Bhandary, Bidur; Jeong, Seul-Ki; Kim, Hyung-Ryong; Chae, Han-Jung

    2014-03-12

    The aim of this study was to investigate the effects of soy on the pharmacokinetics and pharmacodynamics of valproic acid (VPA). In a preclinical study, rats were pretreated with two different amounts of soy extract for five days (150 mg/kg and 500 mg/kg), which resulted in decreases of 57% and 65% in the Cmax of VPA, respectively. AUC of VPA decreased to 83% and 70% in the soy pretreatment groups. Interestingly, the excretion rate of VPA glucuronide (VPAG) was higher in the soy-fed groups. Levels of UDP-glucuronosyltransferase (UGT) UGT1A3, UGT1A6, UGT2B7 and UGT2B15 were elevated in the soy-treated group, and GABA concentrations were elevated in the brain after VPA administration. However, this was less pronounced in soy extract pretreated group than for the untreated group. This is the first study to report the effects of soy pretreatment on the pharmacokinetics and pharmacodynamics of VPA in rodents.

  5. 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,…

  6. 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

  7. Serum concentrations of psychotropic drugs in neonates as a PROgnOstic Factor for admission to the neonatology ward and withdrawal symptoms: PROOF-1.

    Science.gov (United States)

    Sparla, Shirley C A; Coppens, Hans; Evers, Inge M; Stramrood, Claire A I; Pasker-de Jong, Pieternel C M; van der Westerlaken, Monique M L; Hogeman, Paul H G; Malingré, Mirte M

    2017-05-01

    The aim is to determine whether serum drug concentrations obtained from the neonate's umbilical cord can be used as a prognostic factor for admission to the neonatology ward and the occurrence of withdrawal symptoms. A retrospective observational monocenter cohort study was carried out among pregnant women using psychotropic drugs and their baby. Binary logistic regression was used for the multivariate analysis. Of the 186 neonates included, 22.6% (n=42) were admitted to the neonatology ward, 6.5% (n=12) because of withdrawal. Among women with therapeutic concentrations of psychotropic medication, 22.0% (n=5) of the neonates had withdrawal symptoms. When comparing neonates with therapeutic versus undetectable drug concentrations, an odds ratio of 3.1 (95% confidence interval: 1.1-8.6) was found for admission to the neonatology ward and an odds ratio of 20.5 (95% confidence interval: 2.2-186.1) for the occurrence of withdrawal symptoms. Therapeutic concentrations of psychotropic drugs in neonates' umbilical cord blood correspond with higher odds for admission to the neonatology ward and the occurrence of withdrawal symptoms compared with neonates with undetectable drug concentrations. The measurement of drug concentrations in the neonate may contribute toward the general clinical assessment of the physician to predict the necessity of admission to the neonatology ward and the risk of withdrawal symptoms.

  8. 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

  9. 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

  10. Doxorubicin-loaded QuadraSphere microspheres: plasma pharmacokinetics and intratumoral drug concentration in an animal model of liver cancer.

    Science.gov (United States)

    Lee, Kwang-Hun; Liapi, Eleni A; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A; Ventura, Veronica Prieto; Geschwind, Jean-Francois H

    2010-06-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  11. Doxorubicin-Loaded QuadraSphere Microspheres: Plasma Pharmacokinetics and Intratumoral Drug Concentration in an Animal Model of Liver Cancer

    International Nuclear Information System (INIS)

    Lee, Kwang-Hun; Liapi, Eleni A.; Cornell, Curt; Reb, Philippe; Buijs, Manon; Vossen, Josephina A.; Ventura, Veronica Prieto; Geschwind, Jean-Francois H.

    2010-01-01

    The purpose of this study was to evaluate, in vitro and in vivo, doxorubicin-loaded poly (vinyl alcohol-sodium acrylate) copolymer microspheres [QuadraSphere microspheres (QSMs)] for transcatheter arterial delivery in an animal model of liver cancer. Doxorubicin loading efficiency and release profile were first tested in vitro. In vivo, 15 rabbits, implanted with a Vx-2 tumor in the liver, were divided into three groups of five rabbits each, based on the time of euthanasia. Twenty-five milligrams of QSMs was diluted in 10 ml of a 10 mg/ml doxorubicin solution and 10 ml of nonionic contrast medium for a total volume of 20 ml. One milliliter of a drug-loaded QSM solution containing 5 mg of doxorubicin was injected into the tumor feeding artery. Plasma doxorubicin and doxorubicinol concentrations, and intratumoral and peritumoral doxorubicin tissue concentrations, were measured. Tumor specimens were pathologically evaluated to record tumor necrosis. As a control, one animal was blandly embolized with plain QSMs in each group. In vitro testing of QSM doxorubicin loadability and release over time showed 82-94% doxorubicin loadability within 2 h and 6% release within the first 6 h after loading, followed by a slow release pattern. In vivo, the doxorubicin plasma concentration declined at 40 min. The peak doxorubicin intratumoral concentration was observed at 3 days and remained detectable till the study's end point (7 days). Mean percentage tumor cell death in the doxorubicin QSM group was 90% at 7 days and 60% in the bland QSM embolization group. In conclusion, QSMs can be efficiently loaded with doxorubicin. Initial experiments with doxorubicin-loaded QSMs show a safe pharmacokinetic profile and effective tumor killing in an animal model of liver cancer.

  12. 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

  13. 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

  14. 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

  15. Efficient purification and concentration of viruses from a large body of high turbidity seawater.

    Science.gov (United States)

    Sun, Guowei; Xiao, Jinzhou; Wang, Hongming; Gong, Chaowen; Pan, Yingjie; Yan, Shuling; Wang, Yongjie

    2014-01-01

    Marine viruses are the most abundant entities in the ocean and play crucial roles in the marine ecological system. However, understanding of viral diversity on large scale depends on efficient and reliable viral purification and concentration techniques. Here, we report on developing an efficient method to purify and concentrate viruses from large body of high turbidity seawater. The developed method characterizes with high viral recovery efficiency, high concentration factor, high viral particle densities and high-throughput, and is reliable for viral concentration from high turbidity seawater. Recovered viral particles were used directly for subsequent analysis by epifluorescence microscopy, transmission electron microscopy and metagenomic sequencing. Three points are essential for this method:•The sampled seawater (>150 L) was initially divided into two parts, water fraction and settled matter fraction, after natural sedimentation.•Both viruses in the water fraction concentrated by tangential flow filtration (TFF) and viruses isolated from the settled matter fraction were considered as the whole viral community in high turbidity seawater.•The viral concentrates were re-concentrated by using centrifugal filter device in order to obtain high density of viral particles.

  16. 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.

  17. 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.

  18. 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.

  19. High concentration suspended sediment measurments using acontinuous fiber optic in-stream transmissometer

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, Chris G.; Laycak, Danny T.; Hoppes, William; Tran,Nguyen T.; Shi, Frank G.

    2004-05-26

    Suspended sediment loads mobilized during high flow periods in rivers and streams are largely uncharacterized. In smaller and intermittent streams, a large storm may transport a majority of the annual sediment budget. Therefore monitoring techniques that can measure high suspended sediment concentrations at semi-continuous time intervals are needed. A Fiber optic In-stream Transmissometer (FIT) is presented for continuous measurement of high concentration suspended sediment in storm runoff. FIT performance and precision were demonstrated to be reasonably good for suspended sediment concentrations up to 10g/L. The FIT was compared to two commercially available turbidity devices and provided better precision and accuracy at both high and low concentrations. Both turbidity devices were unable to collect measurements at concentrations greater than 4 g/L. The FIT and turbidity measurements were sensitive to sediment particle size. Particle size dependence of transmittance and turbidity measurement poses the greatest problem for calibration to suspended sediment concentration. While the FIT was demonstrated to provide acceptable measurements of high suspended sediment concentrations, approaches to real-time suspended sediment detection need to address the particle size dependence in concentration measurements.

  20. Rheology of dilute acid hydrolyzed corn stover at high solids concentration.

    Science.gov (United States)

    Ehrhardt, M R; Monz, T O; Root, T W; Connelly, R K; Scott, C T; Klingenberg, D J

    2010-02-01

    The rheological properties of acid hydrolyzed corn stover at high solids concentration (20-35 wt.%) were investigated using torque rheometry. These materials are yield stress fluids whose rheological properties can be well represented by the Bingham model. Yield stresses increase with increasing solids concentration and decrease with increasing hydrolysis reaction temperature, acid concentration, and rheometer temperature. Plastic viscosities increase with increasing solids concentration and tend to decrease with increasing reaction temperature and acid concentration. The solids concentration dependence of the yield stress is consistent with that reported for other fibrous systems. The changes in yield stress with reaction conditions are consistent with observed changes in particle size. This study illustrates that torque rheometry can be used effectively to measure rheological properties of concentrated biomass.

  1. Novel DDR Processing of Corn Stover Achieves High Monomeric Sugar Concentrations from Enzymatic Hydrolysis (230 g/L) and High Ethanol Concentration (10% v/v) During Fermentation

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Xiaowen; Jennings, Ed; Shekiro, Joe; Kuhn, Erik M.; O' Brien, Marykate; Wang, Wei; Schell, Daniel J.; Himmel, Mike; Elander, Richard T.; Tucker, Melvin P.

    2015-04-03

    Distilling and purifying ethanol, butanol, and other products from second and later generation lignocellulosic biorefineries adds significant capital and operating cost for biofuels production. The energy costs associated with distillation affects plant gate and life cycle analysis costs. Lower titers in fermentation due to lower sugar concentrations from pretreatment increase both energy and production costs. In addition, higher titers decrease the volumes required for enzymatic hydrolysis and fermentation vessels. Therefore, increasing biofuels titers has been a research focus in renewable biofuels production for several decades. In this work, we achieved over 200 g/L of monomeric sugars after high solids enzymatic hydrolysis using the novel deacetylation and disc refining (DDR) process on corn stover. The high sugar concentrations and low chemical inhibitor concentrations from the DDR process allowed ethanol titers as high as 82 g/L in 22 hours, which translates into approximately 10 vol% ethanol. To our knowledge, this is the first time that 10 vol% ethanol in fermentation derived from corn stover without any sugar concentration or purification steps has been reported. Techno-economic analysis shows the higher titer ethanol achieved from the DDR process could significantly reduce the minimum ethanol selling price from cellulosic biomass.

  2. Identification of intestinal loss of a drug through physiologically based pharmacokinetic simulation of plasma concentration-time profiles.

    Science.gov (United States)

    Peters, Sheila Annie

    2008-01-01

    Despite recent advances in understanding of the role of the gut as a metabolizing organ, recognition of gut wall metabolism and/or other factors contributing to intestinal loss of a compound has been a challenging task due to the lack of well characterized methods to distinguish it from first-pass hepatic extraction. The implications of identifying intestinal loss of a compound in drug discovery and development can be enormous. Physiologically based pharmacokinetic (PBPK) simulations of pharmacokinetic profiles provide a simple, reliable and cost-effective way to understand the mechanisms underlying pharmacokinetic processes. The purpose of this article is to demonstrate the application of PBPK simulations in bringing to light intestinal loss of orally administered drugs, using two example compounds: verapamil and an in-house compound that is no longer in development (referred to as compound A in this article). A generic PBPK model, built in-house using MATLAB software and incorporating absorption, metabolism, distribution, biliary and renal elimination models, was employed for simulation of concentration-time profiles. Modulation of intrinsic hepatic clearance and tissue distribution parameters in the generic PBPK model was done to achieve a good fit to the observed intravenous pharmacokinetic profiles of the compounds studied. These optimized clearance and distribution parameters are expected to be invariant across different routes of administration, as long as the kinetics are linear, and were therefore employed to simulate the oral profiles of the compounds. For compounds with reasonably good solubility and permeability, an area under the concentration-time curve for the simulated oral profile that far exceeded the observed would indicate some kind of loss in the intestine. PBPK simulations applied to compound A showed substantial loss of the compound in the gastrointestinal tract in humans but not in rats. This accounted for the lower bioavailability of the

  3. Investigating high-concentration monoclonal antibody powder suspension in nonaqueous suspension vehicles for subcutaneous injection.

    Science.gov (United States)

    Bowen, Mayumi; Armstrong, Nick; Maa, Yuh-Fun

    2012-12-01

    Developing high-concentration monoclonal antibody (mAb) liquid formulations for subcutaneous (s.c.) administration is challenging because increased viscosity makes injection difficult. To overcome this obstacle, we investigated a nonaqueous powder suspension approach. Three IgG1 mAbs were spray dried and suspended at different concentrations in Miglyol® 840, benzyl benzoate, or ethyl lactate. Suspensions were characterized for viscosity, particle size, and syringeability; physical stability was visually inspected. Suspensions generally outperformed liquid solutions for injectability despite higher viscosity at the same mAb concentrations. Powder formulations and properties had little effect on viscosity or injectability. Ethyl lactate suspensions had lowest viscosity (Miglyol® 840 improved overall performance in high mAb concentration suspensions. This study demonstrated the viability of high mAb concentration (>300 mg/mL) in suspension formulations for s.c. administration. Copyright © 2012 Wiley Periodicals, Inc.

  4. 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.

  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. 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

  7. High-concentration mirror-based Kohler integrating system for tandem solar cells

    Science.gov (United States)

    Winston, R.; Benitez, P.; Cvetkovic, A.

    2006-06-01

    A novel two-mirror high concentration nonimaging optic has been designed that shares the advantages of present two mirror aplanatic imaging concentrators but also overcomes their main limitation of trade-off between acceptance angle and irradiance uniformity. A system concept has been defined, and a first prototype in under development.

  8. 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

  9. Tacrolimus concentration/dose ratio as a therapeutic drug monitoring strategy: The influence of gender and comedication

    Directory of Open Access Journals (Sweden)

    Rančić Nemanja

    2015-01-01

    Full Text Available Background/Aim. A combination of tacrolimus and other drugs such as corticosteroids has been commonly used immunosuppresive regimens. On the other hand, there is a growing body of evidence that male and female may differ in their response to the equal drug treatment. The aim of the study was to estimated the use of tacrolimus concentration/dose (C/D ratio for the assessment of the influence of gender differences and comedication on tacrolimus exposure in renal transplant recipients. Methods. This prospective case series study included 54 patients, in which the unit of monitoring was outpatient examination (1,872 of the renal transplant patients. The patients were monitored in the period 2010-2014, starting one month after the transplantation. Tacrolimus trough concentrations (TTC were measured by chemiluminescence microparticles immunoassay. Results. TTC and the tacrolimus C/D ratio were significantly lower in the females comparing with the males. Contrary to the males, in the females a significant increase of the tacrolimus daily dose (TDD per body weight and TTC, along with the corticosteroid dose increase, was not accompanied by any significant changes in the tacrolimus C/D ratio; in different corticosteroid doses faster elimination of tacrolimus was found with the exception of the doses > 0.25 mg/kg. In the patients treated with proton pump inhibitors, mainly with pantoprazole TDD per body weight and TTC were significantly higher, while the tacrolimus C/D ratio was significantly lower compared to the patients without this treatment. In the patients treated with calcium channel blockers, TDD per body weight was significantly lower (particularly with amlodipine while the tacrolimus C/D ratio was higher compared to the patients who were not treated by them. Conclusion. A lower tacrolimus exposure was detected in females in comparison to males. When gender differences were considered in the context of different corticosteroid doses, faster

  10. HCS-Neurons: identifying phenotypic changes in multi-neuron images upon drug treatments of high-content screening.

    Science.gov (United States)

    Charoenkwan, Phasit; Hwang, Eric; Cutler, Robert W; Lee, Hua-Chin; Ko, Li-Wei; Huang, Hui-Ling; Ho, Shinn-Ying

    2013-01-01

    High-content screening (HCS) has become a powerful tool for drug discovery. However, the discovery of drugs targeting neurons is still hampered by the inability to accurately identify and quantify the phenotypic changes of multiple neurons in a single image (named multi-neuron image) of a high-content screen. Therefore, it is desirable to develop an automated image analysis method for analyzing multi-neuron images. We propose an automated analysis method with novel descriptors of neuromorphology features for analyzing HCS-based multi-neuron images, called HCS-neurons. To observe multiple phenotypic changes of neurons, we propose two kinds of descriptors which are neuron feature descriptor (NFD) of 13 neuromorphology features, e.g., neurite length, and generic feature descriptors (GFDs), e.g., Haralick texture. HCS-neurons can 1) automatically extract all quantitative phenotype features in both NFD and GFDs, 2) identify statistically significant phenotypic changes upon drug treatments using ANOVA and regression analysis, and 3) generate an accurate classifier to group neurons treated by different drug concentrations using support vector machine and an intelligent feature selection method. To evaluate HCS-neurons, we treated P19 neurons with nocodazole (a microtubule depolymerizing drug which has been shown to impair neurite development) at six concentrations ranging from 0 to 1000 ng/mL. The experimental results show that all the 13 features of NFD have statistically significant difference with respect to changes in various levels of nocodazole drug concentrations (NDC) and the phenotypic changes of neurites were consistent to the known effect of nocodazole in promoting neurite retraction. Three identified features, total neurite length, average neurite length, and average neurite area were able to achieve an independent test accuracy of 90.28% for the six-dosage classification problem. This NFD module and neuron image datasets are provided as a freely downloadable

  11. Development of automatic high-concentration boron measurement technique; Konodo hoso jido sokutei gijutsu no kaihatsu

    Energy Technology Data Exchange (ETDEWEB)

    Maeda, T.; Honda, S.; Ito, A. [Kyushu Electric Power Co. Inc., Fukuoka (Japan)

    1997-03-01

    The technology that can automatically measure the boron concentration in boric acid water was developed. A high-concentration boric acid solution must be held at a high temperature to prevent the deposition. Skill and precision ({plus_minus}0.2 to 0.3% for 10 to 2500 ppm as boron concentration, and {plus_minus}2 to 3% for 2500 to 25,000 ppm) are required to analyze the boric acid solution manually. In theory, the boron concentration in a wide range can be measured, and boron has a constant-temperature function. A density hydrometer method that facilitates the treatment and calibration in high precision and at low cost was chosen. The vibration period generated when vibration is given to the solution specimen put in a U-tube is higher as the density is lower. On the basis of this theory, the density of a specimen can be obtained according to the relation with the same data of the known-concentration boric acid water. The high-concentration boric acid water that cannot be measured by the existing boron densitometer can be measured directly. It can also be measured in a low-concentration area. The technique can be used in a laboratory as the simplified method that is replaced by the current manual analysis. The reduction effect of analytical chemical`s waste liquid can also be expected. In the electric power industry, automated equipment is required for high efficiency and labor saving. 13 figs., 3 tabs.

  12. Using fractional extraction method to separate Mo from U in high concentration solution

    International Nuclear Information System (INIS)

    Zhao Pinzhi; Cheng Guangrong; Ma Xiuhua

    1996-01-01

    The author presents investigation on separating Mo from U in acid high concentration lixivium with fractional extraction of secondary amine (7203) and D2EHPA and preparing qualified products of ammonium molybdate and sodium diuranate

  13. Andrographis paniculata Extract and Andrographolide Modulate the Hepatic Drug Metabolism System and Plasma Tolbutamide Concentrations in Rats

    Directory of Open Access Journals (Sweden)

    Haw-Wen Chen

    2013-01-01

    Full Text Available Andrographolide is the most abundant terpenoid of A. paniculata which is used in the treatment of diabetes. In this study, we investigated the effects of A. paniculata extract (APE and andrographolide on the expression of drug-metabolizing enzymes in rat liver and determined whether modulation of these enzymes changed the pharmacokinetics of tolbutamide. Rats were intragastrically dosed with 2 g/kg/day APE or 50 mg/kg/day andrographolide for 5 days before a dose of 20 mg/kg tolbutamide was given. APE and andrographolide reduced the AUC0–12 h of tolbutamide by 37% and 18%, respectively, compared with that in controls. The protein and mRNA levels and enzyme activities of CYP2C6/11, CYP1A1/2, and CYP3A1/2 were increased by APE and andrographolide. To evaluate whether APE or andrographolide affected the hypoglycemic action of tolbutamide, high-fat diet-induced obese mice were used and treated in the same manner as the rats. APE and andrographolide increased CYP2C6/11 expression and decreased plasma tolbutamide levels. In a glucose tolerance test, however, the hypoglycemic effect of tolbutamide was not changed by APE or andrographolide. These results suggest that APE and andrographolide accelerate the metabolism rate of tolbutamide through increased expression and activity of drug-metabolizing enzymes. APE and andrographolide, however, do not impair the hypoglycemic effect of tolbutamide.

  14. Application of Hydrothermal Treatment to High Concentrated Sewage Sludge for Anaerobic Digestion Process

    OpenAIRE

    M. Orikawa; H. Kamahara; Y. Atsuta; H. Daimon

    2013-01-01

    Tomato and seaweed were produced by utilizing CO2 and heat discharged from power generation using biogas in Toyogawa biomass park, Japan. The biogas was obtained by anaerobic digestion with hydrothermal treatment. The hydrothermal treatment was applied to the high concentrated sewage sludge (22 % total solids (TS) dewatered sludge). The purpose of this study is to clarify the effect of hydrothermal treatment on the qualities of high concentrated sewage sludge, by analyzing particulate organic...

  15. High surface hole concentration p-type GaN using Mg implantation

    International Nuclear Information System (INIS)

    Long Tao; Yang Zhijian; Zhang Guoyi

    2001-01-01

    Mg ions were implanted on Mg-doped GaN grown by metalorganic chemical vapor deposition (MOCVD). The p-type GaN was achieved with high hole concentration (8.28 x 10 17 cm -3 ) conformed by Van derpauw Hall measurement after annealing at 800 degree C for 1 h. this is the first experimental report of Mg implantation on Mg-doped GaN and achieving p-type GaN with high surface hole concentration

  16. Compact high-flux two-stage solar collectors based on tailored edge-ray concentrators

    Science.gov (United States)

    Friedman, Robert P.; Gordon, Jeffrey M.; Ries, Harald

    1995-08-01

    Using the recently-invented tailored edge-ray concentrator (TERC) approach for the design of compact two-stage high-flux solar collectors--a focusing primary reflector and a nonimaging TERC secondary reflector--we present: 1) a new primary reflector shape based on the TERC approach and a secondary TERC tailored to its particular flux map, such that more compact concentrators emerge at flux concentration levels in excess of 90% of the thermodynamic limit; and 2) calculations and raytrace simulations result which demonstrate the V-cone approximations to a wide variety of TERCs attain the concentration of the TERC to within a few percent, and hence represent practical secondary concentrators that may be superior to corresponding compound parabolic concentrator or trumpet secondaries.

  17. A Physiologically Based Pharmacokinetic Model to Predict the Pharmacokinetics of Highly Protein-Bound Drugs and Impact of Errors in Plasma Protein Binding

    Science.gov (United States)

    Ye, Min; Nagar, Swati; Korzekwa, Ken

    2015-01-01

    Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data was often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding, and blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for terminal elimination half-life (t1/2, 100% of drugs), peak plasma concentration (Cmax, 100%), area under the plasma concentration-time curve (AUC0–t, 95.4%), clearance (CLh, 95.4%), mean retention time (MRT, 95.4%), and steady state volume (Vss, 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. PMID:26531057

  18. A physiologically based pharmacokinetic model to predict the pharmacokinetics of highly protein-bound drugs and the impact of errors in plasma protein binding.

    Science.gov (United States)

    Ye, Min; Nagar, Swati; Korzekwa, Ken

    2016-04-01

    Predicting the pharmacokinetics of highly protein-bound drugs is difficult. Also, since historical plasma protein binding data were often collected using unbuffered plasma, the resulting inaccurate binding data could contribute to incorrect predictions. This study uses a generic physiologically based pharmacokinetic (PBPK) model to predict human plasma concentration-time profiles for 22 highly protein-bound drugs. Tissue distribution was estimated from in vitro drug lipophilicity data, plasma protein binding and the blood: plasma ratio. Clearance was predicted with a well-stirred liver model. Underestimated hepatic clearance for acidic and neutral compounds was corrected by an empirical scaling factor. Predicted values (pharmacokinetic parameters, plasma concentration-time profile) were compared with observed data to evaluate the model accuracy. Of the 22 drugs, less than a 2-fold error was obtained for the terminal elimination half-life (t1/2 , 100% of drugs), peak plasma concentration (Cmax , 100%), area under the plasma concentration-time curve (AUC0-t , 95.4%), clearance (CLh , 95.4%), mean residence time (MRT, 95.4%) and steady state volume (Vss , 90.9%). The impact of fup errors on CLh and Vss prediction was evaluated. Errors in fup resulted in proportional errors in clearance prediction for low-clearance compounds, and in Vss prediction for high-volume neutral drugs. For high-volume basic drugs, errors in fup did not propagate to errors in Vss prediction. This is due to the cancellation of errors in the calculations for tissue partitioning of basic drugs. Overall, plasma profiles were well simulated with the present PBPK model. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. High interpatient variability of raltegravir CSF concentrations in HIV-positive patients: a pharmacogenetic analysis.

    Science.gov (United States)

    Calcagno, Andrea; Cusato, Jessica; Simiele, Marco; Motta, Ilaria; Audagnotto, Sabrina; Bracchi, Margherita; D'Avolio, Antonio; Di Perri, Giovanni; Bonora, Stefano

    2014-01-01

    To analyse the determinants of raltegravir CSF penetration, including the pharmacogenetics of drug transporters located at the blood-brain barrier or blood-CSF barrier. Plasma and CSF raltegravir concentrations were determined by a validated HPLC coupled with mass spectrometry method in adults on raltegravir-based combination antiretroviral therapy undergoing a lumbar puncture. Single nucleotide polymorphisms in the genes encoding drugs transporters (ABCB1 3435, SLCO1A2, ABCC2 and SLC22A6) and the gene encoding hepatocyte nuclear factor 4 α (HNF4α) were determined by real-time PCR. In 41 patients (73.2% male, 95.1% Caucasians), the median raltegravir plasma and CSF concentrations were 165 ng/mL (83-552) and 31 ng/mL (21-56), respectively. CSF-to-plasma ratios (CPRs) ranged from 0.005 to 1.33 (median 0.20, IQR 0.04-0.36). Raltegravir trough CSF concentrations (n = 35) correlated with raltegravir plasma levels (ρ = 0.395, P = 0.019); CPRs were higher in patients with blood-brain barrier damage (0.47 versus 0.18, P = 0.02). HNF4α 613 CG genotype carriers had lower trough CSF concentrations (20 versus 37 ng/mL, P = 0.03) and CPRs (0.12 versus 0.27, P = 0.02). Following multivariate linear regression analysis, the CSF-to-serum albumin ratio was the only independent predictor of raltegravir penetration into the CSF. Raltegravir penetration into the CSF shows a large interpatient variability, although CSF concentrations were above the wild-type IC50 in all patients (and above IC95 in 28.6%). In this cohort, blood-brain barrier permeability is the only independent predictor of raltegravir CPR. The impact of single nucleotide polymorphisms in selected genes on raltegravir penetration warrants further studies.

  20. 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

  1. Gravitational settling of a highly concentrated system of solid spherical particles

    Science.gov (United States)

    Arkhipov, V. A.; Usanina, A. S.

    2017-09-01

    In the present paper, we report on the results of an experimental study of the process of gravity sedimentation of a cloud of monodispersed solid spherical particles with initial volume concentration C > 0.03, which was performed in a wide range of Reynolds numbers. An analytical estimate of the settling regimes of spherical particle clouds is presented. A new method for creating a spherical particle cloud with a high concentration of particles is proposed. A qualitative picture of the settling process of a highly concentrated particle cloud under gravity is revealed. A criterial dependence for the drag coefficient of a sedimenting spherical particle cloud as an entity is obtained.

  2. Suboptimal Antituberculosis Drug Concentrations and Outcomes in Small and HIV-Coinfected Children in India: Recommendations for Dose Modifications.

    Science.gov (United States)

    Guiastrennec, Benjamin; Ramachandran, Geetha; Karlsson, Mats O; Kumar, A K Hemanth; Bhavani, Perumal Kannabiran; Gangadevi, N Poorana; Swaminathan, Soumya; Gupta, Amita; Dooley, Kelly E; Savic, Radojka M

    2017-12-16

    This work aimed to evaluate the once-daily antituberculosis treatment as recommended by the new Indian pediatric guidelines. Isoniazid, rifampin, and pyrazinamide concentration-time profiles and treatment outcome were obtained from 161 Indian children with drug-sensitive tuberculosis undergoing thrice-weekly dosing as per previous Indian pediatric guidelines. The exposure-response relationships were established using a population pharmacokinetic-pharmacodynamic approach. Rifampin exposure was identified as the unique predictor of treatment outcome. Consequently, children with low body weight (4-7 kg) and/or HIV infection, who displayed the lowest rifampin exposure, were associated with the highest probability of unfavorable treatment (therapy failure, death) outcome (P unfavorable ). Model-based simulation of optimized (P unfavorable ≤ 5%) rifampin once-daily doses were suggested per treatment weight band and HIV coinfection status (33% and 190% dose increase, respectively, from the new Indian guidelines). The established dose-exposure-response relationship could be pivotal in the development of future pediatric tuberculosis treatment guidelines. © 2017, The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  3. Postmortem Blood Concentrations of R- and S-Enantiomers of Methadone and EDDP in Drug Users: Influence of Co-Medication and P-glycoprotein Genotype

    DEFF Research Database (Denmark)

    Buchard, Anders; Linnet, Kristian; Johansen, Sys Stybe

    2010-01-01

    We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S-enantiome......We investigated toxicological and pharmacogenetic factors that could influence methadone toxicity using postmortem samples. R- and S-methadone were measured in femoral blood from 90 postmortem cases, mainly drug users. The R-enantiomer concentrations significantly exceeded that of the S...

  4. Real-time investigation of human topoisomerase I reaction kinetics using an optical sensor: a fast method for drug screening and determination of active enzyme concentrations

    Science.gov (United States)

    Kristoffersen, Emil L.; Jørgensen, Line A.; Franch, Oskar; Etzerodt, Michael; Frøhlich, Rikke; Bjergbæk, Lotte; Stougaard, Magnus; Ho, Yi-Ping; Knudsen, Birgitta R.

    2015-05-01

    Human DNA topoisomerase I (hTopI) is a nuclear enzyme that catalyzes relaxation of super helical tension that arises in the genome during essential DNA metabolic processes. This is accomplished through a common reaction mechanism shared among the type IB topoisomerase enzymes, including eukaryotic and poxvirus topoisomerase I. The mechanism of hTopI is specifically targeted in cancer treatment using camptothecin derivatives. These drugs convert the hTopI activity into a cellular poison, and hence the cytotoxic effects of camptothecin derivatives correlate with the hTopI activity. Therefore, fast and reliable techniques for high throughput measurements of hTopI activity are of high clinical interest. Here we demonstrate potential applications of a fluorophore-quencher based DNA sensor designed for measurement of hTopI cleavage-ligation activities, which are the catalytic steps affected by camptothecin. The kinetic analysis of the hTopI reaction with the DNA sensor exhibits a characteristic burst profile. This is the result of a two-step ping-pong reaction mechanism, where a fast first reaction, the one creating the signal, is followed by a slower second reaction necessary for completion of the catalytic cycle. Hence, the burst profile holds information about two reactions in the enzymatic mechanism. Moreover, it allows the amount of active enzyme in the reaction to be determined. The presented results pave the way for future high throughput drug screening and the potential of measuring active hTopI concentrations in clinical samples for individualized treatment.Human DNA topoisomerase I (hTopI) is a nuclear enzyme that catalyzes relaxation of super helical tension that arises in the genome during essential DNA metabolic processes. This is accomplished through a common reaction mechanism shared among the type IB topoisomerase enzymes, including eukaryotic and poxvirus topoisomerase I. The mechanism of hTopI is specifically targeted in cancer treatment using

  5. Determination of trace concentrations of chlorine in aqueous solutions by high-resolution continuum source graphite furnace molecular absorption spectrometry

    Science.gov (United States)

    Machyňák, Ľubomír; Čacho, František; Němeček, Martin; Beinrohr, Ernest

    2016-11-01

    Trace concentrations of total chlorine were determined by means of molecular absorption of indium mono-chloride (InCl) at 267.217 nm using high-resolution continuum source graphite furnace molecular absorption spectrometry. The effects of chemical modifiers and the amount of In on the sensitivity and accuracy were investigated. The optimum pyrolysis and vaporization temperatures were 600 °C and 1400 °C, respectively. The limit of detection and characteristic mass were found to be 0.10 ng and 0.21 ng, respectively. Potential non-spectral and spectral interferences were tested for various metals and non-metals at concentrations up to 50 mg L- 1 and for phosphoric, sulphuric and nitric acids. No spectral interferences were observed. Significant non-spectral interferences were observed with F, Br, and I at concentrations higher than 1 mg L- 1, 5 mg L- 1 and 25 mg L- 1, respectively, which is probably caused by formation of competitive indium halogen molecules. Higher concentrations of mineral acids depressed the signal owing to the formation of volatile HCl. The calibration curve was linear in the range between 0.3 and 10 ng with a correlation coefficient of R = 0.993. The elaborated method was used for the chlorine determination in various waters and a drug sample.

  6. 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

  7. Real-time investigation of human topoisomerase I reaction kinetics using an optical sensor: a fast method for drug screening and determination of active enzyme concentrations.

    Science.gov (United States)

    Kristoffersen, Emil L; Jørgensen, Line A; Franch, Oskar; Etzerodt, Michael; Frøhlich, Rikke; Bjergbæk, Lotte; Stougaard, Magnus; Ho, Yi-Ping; Knudsen, Birgitta R

    2015-06-07

    Human DNA topoisomerase I (hTopI) is a nuclear enzyme that catalyzes relaxation of super helical tension that arises in the genome during essential DNA metabolic processes. This is accomplished through a common reaction mechanism shared among the type IB topoisomerase enzymes, including eukaryotic and poxvirus topoisomerase I. The mechanism of hTopI is specifically targeted in cancer treatment using camptothecin derivatives. These drugs convert the hTopI activity into a cellular poison, and hence the cytotoxic effects of camptothecin derivatives correlate with the hTopI activity. Therefore, fast and reliable techniques for high throughput measurements of hTopI activity are of high clinical interest. Here we demonstrate potential applications of a fluorophore-quencher based DNA sensor designed for measurement of hTopI cleavage-ligation activities, which are the catalytic steps affected by camptothecin. The kinetic analysis of the hTopI reaction with the DNA sensor exhibits a characteristic burst profile. This is the result of a two-step ping-pong reaction mechanism, where a fast first reaction, the one creating the signal, is followed by a slower second reaction necessary for completion of the catalytic cycle. Hence, the burst profile holds information about two reactions in the enzymatic mechanism. Moreover, it allows the amount of active enzyme in the reaction to be determined. The presented results pave the way for future high throughput drug screening and the potential of measuring active hTopI concentrations in clinical samples for individualized treatment.

  8. 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

  9. Usefulness of saliva for measurement of 3,4-methylenedioxymethamphetamine and its metabolites: correlation with plasma drug concentrations and effect of salivary pH.

    Science.gov (United States)

    Navarro, M; Pichini, S; Farré, M; Ortuño, J; Roset, P N; Segura, J; de la Torre, R

    2001-10-01

    Saliva is an alternative biologic matrix for drugs-of-abuse testing that offers the advantages of noninvasive, rapid, and easy sampling. We studied the excretion profile of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolites in both saliva and plasma, as well the effect of the drug on salivary pH. Saliva and plasma samples were obtained from eight healthy MDMA consumers after ingestion of a single 100-mg dose of the drug. Concentrations of MDMA and its main metabolites, 3,4-methylenedioxyamphetamine (MDA) and 4-hydroxy-3-methoxymethamphetamine (HMMA), in saliva and plasma were measured by gas chromatography-mass spectrometry. Apparent pharmacokinetic parameters for MDMA in saliva were estimated, and the saliva-to-plasma ratio at each time interval was calculated and correlated with salivary pH. MDMA, MDA, and HMMA were detected in saliva. Salivary concentrations of MDMA were 1728.9-6510.6 microg/L and peaked at 1.5 h after drug intake. This was followed by a progressive decrease, with a mean concentration of 126.2 microg/L at 24 h. The saliva-to-plasma ratio was 32.3-1.2, with a peak of 18.1 at 1.5 h after drug administration. Salivary pH seemed to be affected by MDMA administration; pH values decreased by 0.6 units (mean pH values of 6.9 and 6.8 at 1.5 and 4 h after drug administration vs predose pH of 7.4). Measurement of MDMA in saliva is a valuable alternative to determination of plasma drug concentrations in both clinical and toxicologic studies. On-site testing is also facilitated by noninvasive and rapid collection of salivary specimens.

  10. 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.

  11. 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…

  12. 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.

  13. High serum uric acid concentration predicts poor survival in patients with breast cancer.

    Science.gov (United States)

    Yue, Cai-Feng; Feng, Pin-Ning; Yao, Zhen-Rong; Yu, Xue-Gao; Lin, Wen-Bin; Qian, Yuan-Min; Guo, Yun-Miao; Li, Lai-Sheng; Liu, Min

    2017-10-01

    Uric acid is a product of purine metabolism. Recently, uric acid has gained much attraction in cancer. In this study, we aim to investigate the clinicopathological and prognostic significance of serum uric acid concentration in breast cancer patients. A total of 443 female patients with histopathologically diagnosed breast cancer were included. After a mean follow-up time of 56months, survival was analysed using the Kaplan-Meier method. To further evaluate the prognostic significance of uric acid concentrations, univariate and multivariate Cox regression analyses were applied. Of the clinicopathological parameters, uric acid concentration was associated with age, body mass index, ER status and PR status. Univariate analysis identified that patients with increased uric acid concentration had a significantly inferior overall survival (HR 2.13, 95% CI 1.15-3.94, p=0.016). In multivariate analysis, we found that high uric acid concentration is an independent prognostic factor predicting death, but insufficient to predict local relapse or distant metastasis. Kaplan-Meier analysis indicated that high uric acid concentration is related to the poor overall survival (p=0.013). High uric acid concentration predicts poor survival in patients with breast cancer, and might serve as a potential marker for appropriate management of breast cancer patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Parallel monitoring of plasma and intraluminal drug concentrations in man after oral administration of fosamprenavir in the fasted and fed state.

    Science.gov (United States)

    Brouwers, Joachim; Tack, Jan; Augustijns, Patrick

    2007-10-01

    The purpose of this study was to explore the feasibility of linking the pharmacokinetic profile of a drug with its gastrointestinal behavior by simultaneously monitoring plasma and intraluminal drug concentrations. Fosamprenavir, a phosphate ester prodrug of the poorly water-soluble HIV-inhibitor amprenavir, was selected as model compound. A single tablet of fosamprenavir (Telzir) was administered to 5 volunteers in the fasted and fed state (simulated by intake of a nutritional drink). Gastric and duodenal fluids were aspirated in function of time and characterized with respect to the concentration of (fos)amprenavir, inorganic phosphate and pH. In parallel, blood samples were collected and analyzed for amprenavir. The observed plasma concentration-time profiles suggested a food-induced delay in the absorption of amprenavir: in the fed state, mean tmax increased by more than 150 min compared to the fasted state. A similar delay was seen in the duodenal appearance of fosamprenavir (concentrations in mM-range) and, after dephosphorylation, amprenavir (concentrations below 160 microM). This observation could be related to the behavior of fosamprenavir in the stomach. In the fasted state, gastric dissolution of fosamprenavir started immediately, resulting in a Cmax of 4 +/- 2 mM after 43 +/- 15 min; however, in the fed state, the fosamprenavir concentration remained below 20 microM for the first 90 min after drug intake. The postponed gastric dissolution may be attributed to a food-induced delay in tablet disintegration. For the first time, the pharmacokinetic profile of a drug was monitored in parallel with its gastrointestinal concentrations. The observed food effect in the plasma concentration-time profile of amprenavir after intake of its phosphate ester prodrug could be related to a food-induced delay in gastric dissolution of fosamprenavir.

  15. Study on high concentration solar concentrator using a Fresnel lens with a secondary concentrator; Fresnel lens to niji shukokei wo mochiita solar chemistry yo kobairitsu shukokei ni kansuru kenkyu

    Energy Technology Data Exchange (ETDEWEB)

    Aihara, T; Suzuki, A; Fujibayashi, K [Tokyo University of Agriculture and Technology, Tokyo (Japan)

    1997-11-25

    A high concentration light collection system for solar chemistry was devised by using an inexpensive Fresnel lens in a primary concentration system and a conical type concentrator in a secondary concentration system. A Fresnel lens alone would not achieve sufficiently high light collecting magnification to attain high temperatures because of restrictions in the opening angle as seen from a focus. Therefore, a secondary concentration system was installed on a focus for an attempt of stopping. Reflection plane of a three-dimensional compound parabolic concentrator (CPC) is a rotary parabolic plane, whose process is expensive because of its surface processing accuracy. Therefore, a conical type concentrator was employed as a secondary concentration system. This system may not be capable of achieving as high concentration as in the CPC, but its shape is simple and it is inexpensive. In its optimization, a complete black body surface placed in vacuum atmosphere was hypothesized as a light concentrating part for the secondary concentration system to calculate heat collecting efficiencies at respective temperature settings. Using simultaneously the secondary concentration system, rather than collecting heat by using a Fresnel lens alone, has attained as high value as from 5.99% (500 degC) to 43.47% (1400 degC). Economical high-temperature heat collection of solar chemistry level may be possible by using a Fresnel lens and a conical secondary concentration system. 1 ref., 7 figs., 2 tabs.

  16. High sugar consumption and poor nutrient intake among drug addicts in Oslo, Norway.

    Science.gov (United States)

    Saeland, M; Haugen, M; Eriksen, F-L; Wandel, M; Smehaugen, A; Böhmer, T; Oshaug, A

    2011-02-01

    Poor dietary habits among drug addicts represent health hazards. However, very few studies have focused on dietary intake as an independent health risk factor in relation to this group. The objective of the present study was to examine the dietary habits of drug addicts living on the fringes of an affluent society. The study focused on food access, food preferences, intake of energy and nutrients, and related nutrient blood concentrations. The respondent group consisted of 123 male and seventy-two female drug addicts, who participated in a cross-sectional study that included a 24 h dietary recall, blood samples, anthropometrical measurements and a semi-structured interview concerning food access and preferences. Daily energy intake varied from 0 to 37 MJ. Food received from charitable sources and friends/family had a higher nutrient density than food bought by the respondents. Added sugar accounted for 30 % of the energy intake, which was mirrored in biomarkers. Sugar and sugar-sweetened food items were preferred by 61 % of the respondents. Of the respondents, 32 % had a TAG concentration above the reference values, while 35 % had a cholesterol concentration beneath the reference values. An elevated serum Cu concentration indicated inflammation among the respondents. Further research on problems related to the diets of drug addicts should focus on dietary habits and aim to uncover connections that may reinforce inebriation and addiction.

  17. 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.

  18. 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.

  19. Methods to assess high-resolution subsurface gas concentrations and gas fluxes in wetland ecosystems

    DEFF Research Database (Denmark)

    Elberling, Bo; Kühl, Michael; Glud, Ronnie Nøhr

    2013-01-01

    The need for measurements of soil gas concentrations and surface fluxes of greenhouse gases at high temporal and spatial resolution in wetland ecosystem has lead to the introduction of several new analytical techniques and methods. In addition to the automated flux chamber methodology for high-re...

  20. Prodigious Effects of Concentration Intensification on Nanoparticle Synthesis: A High-Quality, Scalable Approach

    KAUST Repository

    Williamson, Curtis B.

    2015-12-23

    © 2015 American Chemical Society. Realizing the promise of nanoparticle-based technologies demands more efficient, robust synthesis methods (i.e., process intensification) that consistently produce large quantities of high-quality nanoparticles (NPs). We explored NP synthesis via the heat-up method in a regime of previously unexplored high concentrations near the solubility limit of the precursors. We discovered that in this highly concentrated and viscous regime the NP synthesis parameters are less sensitive to experimental variability and thereby provide a robust, scalable, and size-focusing NP synthesis. Specifically, we synthesize high-quality metal sulfide NPs (<7% relative standard deviation for Cu2-xS and CdS), and demonstrate a 10-1000-fold increase in Cu2-xS NP production (>200 g) relative to the current field of large-scale (0.1-5 g yields) and laboratory-scale (<0.1 g) efforts. Compared to conventional synthesis methods (hot injection with dilute precursor concentration) characterized by rapid growth and low yield, our highly concentrated NP system supplies remarkably controlled growth rates and a 10-fold increase in NP volumetric production capacity (86 g/L). The controlled growth, high yield, and robust nature of highly concentrated solutions can facilitate large-scale nanomanufacturing of NPs by relaxing the synthesis requirements to achieve monodisperse products. Mechanistically, our investigation of the thermal and rheological properties and growth rates reveals that this high concentration regime has reduced mass diffusion (a 5-fold increase in solution viscosity), is stable to thermal perturbations (64% increase in heat capacity), and is resistant to Ostwald ripening.

  1. High nitrate concentrations in some Midwest United States streams in 2013 after the 2012 drought

    Science.gov (United States)

    Van Metre, Peter C.; Frey, Jeffrey W.; Musgrove, MaryLynn; Nakagaki, Naomi; Qi, Sharon L.; Mahler, Barbara J.; Wieczorek, Michael; Button, Daniel T.

    2016-01-01

    Nitrogen sources in the Mississippi River basin have been linked to degradation of stream ecology and to Gulf of Mexico hypoxia. In 2013, the USGS and the USEPA characterized water quality stressors and ecological conditions in 100 wadeable streams across the midwestern United States. Wet conditions in 2013 followed a severe drought in 2012, a weather pattern associated with elevated nitrogen concentrations and loads in streams. Nitrate concentrations during the May to August 2013 sampling period ranged from nitrate concentrations at the 100 sites were compared with May to June concentrations predicted from a regression model developed using historical nitrate data. Observed concentrations for 17 sites, centered on Iowa and southern Minnesota, were outside the 95% confidence interval of the regression-predicted mean, indicating that they were anomalously high. The sites with a nitrate anomaly had significantly higher May to June nitrate concentrations than sites without an anomaly (means, 19.8 and 3.6 mg L−1, respectively) and had higher antecedent precipitation indices, a measure of the departure from normal precipitation, in 2012 and 2013. Correlations between nitrate concentrations and watershed characteristics and nitrogen and oxygen isotopes of nitrate indicated that fertilizer and manure used in crop production, principally corn, were the dominant sources of nitrate. The anomalously high nitrate levels in parts of the Midwest in 2013 coincide with reported higher-than-normal nitrate loads in the Mississippi River.

  2. Relation between CYP2D6 Genotype, Phenotype and Therapeutic Drug Concentrations among Nortriptyline and Venlafaxine Users in Old Age Psychiatry

    NARCIS (Netherlands)

    Berm, E; Kok, R.; Hak, E; Wilffert, B

    2016-01-01

    Objectives: To determine relations between drug concentrations and the cytochrome P450-CYP2D6 genotype or phenotype among elderly patients treated with nortriptyline or venlafaxine. Methods: A post-hoc analysis of a clinical trial was performed. Patients were grouped into phenotypes according to the

  3. A selective electrocatalyst-based direct methanol fuel cell operated at high concentrations of methanol.

    Science.gov (United States)

    Feng, Yan; Liu, Hui; Yang, Jun

    2017-06-01

    Owing to the serious crossover of methanol from the anode to the cathode through the polymer electrolyte membrane, direct methanol fuel cells (DMFCs) usually use dilute methanol solutions as fuel. However, the use of high-concentration methanol is highly demanded to improve the energy density of a DMFC system. Instead of the conventional strategies (for example, improving the fuel-feed system, membrane development, modification of electrode, and water management), we demonstrate the use of selective electrocatalysts to run a DMFC at high concentrations of methanol. In particular, at an operating temperature of 80°C, the as-fabricated DMFC with core-shell-shell Au@Ag 2 S@Pt nanocomposites at the anode and core-shell Au@Pd nanoparticles at the cathode produces a maximum power density of 89.7 mW cm -2 at a methanol feed concentration of 10 M and maintains good performance at a methanol concentration of up to 15 M. The high selectivity of the electrocatalysts achieved through structural construction accounts for the successful operation of the DMFC at high concentrations of methanol.

  4. A selective electrocatalyst–based direct methanol fuel cell operated at high concentrations of methanol

    Science.gov (United States)

    Feng, Yan; Liu, Hui; Yang, Jun

    2017-01-01

    Owing to the serious crossover of methanol from the anode to the cathode through the polymer electrolyte membrane, direct methanol fuel cells (DMFCs) usually use dilute methanol solutions as fuel. However, the use of high-concentration methanol is highly demanded to improve the energy density of a DMFC system. Instead of the conventional strategies (for example, improving the fuel-feed system, membrane development, modification of electrode, and water management), we demonstrate the use of selective electrocatalysts to run a DMFC at high concentrations of methanol. In particular, at an operating temperature of 80°C, the as-fabricated DMFC with core-shell-shell Au@Ag2S@Pt nanocomposites at the anode and core-shell Au@Pd nanoparticles at the cathode produces a maximum power density of 89.7 mW cm−2 at a methanol feed concentration of 10 M and maintains good performance at a methanol concentration of up to 15 M. The high selectivity of the electrocatalysts achieved through structural construction accounts for the successful operation of the DMFC at high concentrations of methanol. PMID:28695199

  5. High frequency measurement of nitrate concentration in the Lower Mississippi River, USA

    Science.gov (United States)

    Duan, Shuiwang; Powell, Rodney T.; Bianchi, Thomas S.

    2014-11-01

    Nutrient concentrations in the Mississippi River have increased dramatically since the 1950s, and high frequency measurements on nitrate concentration are required for accurate load estimations and examinations on nitrate transport and transformation processes. This three year record of high temporal resolution (every 2-3 h) data clearly illustrates the importance of high frequency sampling in improving load estimates and resolving variations in nitrate concentration with river flow and tributary inputs. Our results showed large short-term (days to weeks) variations in nitrate concentration but with no diurnal patterns. A repeatable and pronounced seasonal pattern of nitrate concentration was observed, and showed gradual increases from the lowest values in September (during base-flow), to the highest in June - which was followed by a rapid decrease. This seasonal pattern was only moderately linked with water discharge, and more controlled by nitrogen transformation/export from watershed as well as mixing patterns of the two primary tributaries (the upper Mississippi and the Ohio Rivers), which have distinctly different nitrate concentrations and flow patterns. Based on continuous in situ flow measurements, we estimated 554-886 × 106 kg of nitrate-N was exported from the Mississippi River system during years 2004-2006, which was <9% and <16% lower than U.S. Geological Survey's (USGS) estimates using their LOADEST or composite methods, respectively. USGS methods generally overestimated nitrate loads during rising stages and underestimated the loads during falling stages. While changes in nitrate concentrations in large rivers are generally not as responsive to alterations in diurnal inputs and/or watershed hydrology as small rivers, high-frequency water quality sampling would help in monitoring short-term (days to weeks) variations in nutrient concentration patterns and thus improve the accuracy of nutrient flux estimates.

  6. Development and characterization of high payload combination dry powders of anti-tubercular drugs for treating pulmonary tuberculosis.

    Science.gov (United States)

    Eedara, Basanth Babu; Rangnekar, Bhamini; Sinha, Shubhra; Doyle, Colin; Cavallaro, Alex; Das, Shyamal C

    2018-06-15

    This study aimed to develop a high payload dry powder inhalation formulation containing a combination of the first line anti-tubercular drug, pyrazinamide, and the second line drug, moxifloxacin HCl. Individual powders of pyrazinamide (P SD ) and moxifloxacin (M SD ) and combination powders of the two drugs without (PM) and with 10% l-leucine (PML) and 10% DPPC (PMLD) were produced by spray drying. P SD contained >10 μm crystalline particles and showed poor aerosolization behaviour with a fine particle fraction (FPF) of 18.7 ± 3.4%. PM produced spherical hollow particles with aerodynamic diameter  0.05) compared to PML . Solid state studies and surface elemental analysis by X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry confirmed the surface coating of particles contained amorphous moxifloxacin and both l-leucine and DPPC over crystalline pyrazinamide. Furthermore, pyrazinamide, moxifloxacin, PML and PMLD were found to display low toxicity to both A549 and Calu-3 cell lines even at a concentration of 100 μg/mL. In conclusion, a combination powder formulation of PML has the potential to deliver a high drug dose to the site of infection resulting in efficient treatment. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. 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.

  8. 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.

  9. Clearly Transparent Nanopaper from Highly Concentrated Cellulose Nanofiber Dispersion Using Dilution and Sonication

    Directory of Open Access Journals (Sweden)

    Takaaki Kasuga

    2018-02-01

    Full Text Available Nanopaper prepared from holocellulose pulp is one of the best substrates for flexible electronics because of its high thermal resistance and high clear transparency. However, the clearness of nanopaper decreases with increasing concentration of the starting cellulose nanofiber dispersion—with the use of a 2.2 wt % dispersion, for example—resulting in translucent nanopaper with a high haze of 44%. To overcome this problem, we show that the dilution of this high-concentration dispersion with water followed by sonication for 10 s reduces the haze to less than 10% while maintaining the high thermal resistance of the nanopaper. Furthermore, the combination of water dilution and a short sonication treatment improves the clearness of the nanopaper, which would translate into cost savings for the transportation and storage of this highly concentrated cellulose nanofiber dispersion. Finally, we demonstrate the improvement of the electrical conductivity of clear transparent nanopaper prepared from an initially high-concentration dispersion by dropping and heating silver nanowire ink on the nanopaper. These achievements will pave the way toward the realization of the mass production of nanofiber-based flexible devices.

  10. High Voltage Solar Concentrator Experiment with Implications for Future Space Missions

    Science.gov (United States)

    Mehdi, Ishaque S.; George, Patrick J.; O'Neill, Mark; Matson, Robert; Brockschmidt, Arthur

    2004-01-01

    This paper describes the design, development, fabrication, and test of a high performance, high voltage solar concentrator array. This assembly is believed to be the first ever terrestrial triple-junction-cell solar array rated at over 1 kW. The concentrator provides over 200 W/square meter power output at a nominal 600 Vdc while operating under terrestrial sunlight. Space-quality materials and fabrication techniques were used for the array, and the 3005 meter elevation installation below the Tropic of Cancer allowed testing as close as possible to space deployment without an actual launch. The array includes two concentrator modules, each with a 3 square meter aperture area. Each concentrator module uses a linear Fresnel lens to focus sunlight onto a photovoltaic receiver that uses 240 series-connected triple-junction solar cells. Operation of the two receivers in series can provide 1200 Vdc which would be adequate for the 'direct drive' of some ion engines or microwave transmitters in space. Lens aperture width is 84 cm and the cell active width is 3.2 cm, corresponding to a geometric concentration ratio of 26X. The evaluation includes the concentrator modules, the solar cells, and the materials and techniques used to attach the solar cells to the receiver heat sink. For terrestrial applications, a finned aluminum extrusion was used for the heat sink for the solar cells, maintaining a low cell temperature so that solar cell efficiency remains high.

  11. Structural changes induced by high-pressure processing in micellar casein and milk protein concentrates.

    Science.gov (United States)

    Cadesky, Lee; Walkling-Ribeiro, Markus; Kriner, Kyle T; Karwe, Mukund V; Moraru, Carmen I

    2017-09-01

    Reconstituted micellar casein concentrates and milk protein concentrates of 2.5 and 10% (wt/vol) protein concentration were subjected to high-pressure processing at pressures from 150 to 450 MPa, for 15 min, at ambient temperature. The structural changes induced in milk proteins by high-pressure processing were investigated using a range of physical, physicochemical, and chemical methods, including dynamic light scattering, rheology, mid-infrared spectroscopy, scanning electron microscopy, proteomics, and soluble mineral analyses. The experimental data clearly indicate pressure-induced changes of casein micelles, as well as denaturation of serum proteins. Calcium-binding α S1 - and α S2 -casein levels increased in the soluble phase after all pressure treatments. Pressurization up to 350 MPa also increased levels of soluble calcium and phosphorus, in all samples and concentrations, whereas treatment at 450 MPa reduced the levels of soluble Ca and P. Experimental data suggest dissociation of calcium phosphate and subsequent casein micelle destabilization as a result of pressure treatment. Treatment of 10% micellar casein concentrate and 10% milk protein concentrate samples at 450 MPa resulted in weak, physical gels, which featured aggregates of uniformly distributed, casein substructures of 15 to 20 nm in diameter. Serum proteins were significantly denatured by pressures above 250 MPa. These results provide information on pressure-induced changes in high-concentration protein systems, and may inform the development on new milk protein-based foods with novel textures and potentially high nutritional quality, of particular interest being the soft gel structures formed at high pressure levels. The Authors. Published by the Federation of Animal Science Societies and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

  12. Highly Localized Acoustic Streaming and Size-Selective Submicrometer Particle Concentration Using High Frequency Microscale Focused Acoustic Fields.

    Science.gov (United States)

    Collins, David J; Ma, Zhichao; Ai, Ye

    2016-05-17

    Concentration and separation of particles and biological specimens are fundamental functions of micro/nanofluidic systems. Acoustic streaming is an effective and biocompatible way to create rapid microscale fluid motion and induce particle capture, though the >100 MHz frequencies required to directly generate acoustic body forces on the microscale have traditionally been difficult to generate and localize in a way that is amenable to efficient generation of streaming. Moreover, acoustic, hydrodynamic, and electrical forces as typically applied have difficulty manipulating specimens in the submicrometer regime. In this work, we introduce highly focused traveling surface acoustic waves (SAW) at high frequencies between 193 and 636 MHz for efficient and highly localized production of acoustic streaming vortices on microfluidic length scales. Concentration occurs via a novel mechanism, whereby the combined acoustic radiation and streaming field results in size-selective aggregation in fluid streamlines in the vicinity of a high-amplitude acoustic beam, as opposed to previous acoustic radiation induced particle concentration where objects typically migrate toward minimum pressure locations. Though the acoustic streaming is induced by a traveling wave, we are able to manipulate particles an order of magnitude smaller than possible using the traveling wave force alone. We experimentally and theoretically examine the range of particle sizes that can be captured in fluid streamlines using this technique, with rapid particle concentration demonstrated down to 300 nm diameters. We also demonstrate that locations of trapping and concentration are size-dependent, which is attributed to the combined effects of the acoustic streaming and acoustic forces.

  13. Photoluminescence of highly compensated GaAs doped with high concentration of Ge

    Science.gov (United States)

    Watanabe, Masaru; Watanabe, Akira; Suezawa, Masashi

    1999-12-01

    We have studied the photoluminescence (PL) properties of Ge-doped GaAs crystals to confirm the validity of a theory developed by Shklovskii and Efros to explain the donor-acceptor pair (DAP) recombination in potential fluctuation. GaAs crystals doped with Ge of various concentrations were grown by a liquid-encapsulated Czochralski method. They were homogenized by annealing at 1200°C for 20 h under the optimum As vapor pressure. Both quasi-continuous and time-resolved PL spectra were measured at 4.2 K. The quasi-continuous PL spectra showed that the peak position shifted to lower energy as the Ge concentration increased, which was consistent with the Shklovskii and Efros's theory. Under very strong excitation in time-resolved measurements, the exciton peak appeared within short periods after excitation and then the peak shifted to that of DAP recombination. This clearly showed that the potential fluctuation disappeared under strong excitation and then recovered as the recombination proceeded.

  14. 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.

  15. Storage in high-barrier pouches increases the sulforaphane concentration in broccoli florets.

    Directory of Open Access Journals (Sweden)

    Yoshio Makino

    Full Text Available Sulforaphane is a phytochemical that is usually found in cruciferous vegetables and is known to have a depressive effect on gastric cancer. Preliminary investigations showed that the sulforaphane concentration in broccoli (Brassica oleracea var. italica florets increased under anoxia. Therefore, in the present study, we examined the effect of different atmospheric conditions on the sulforaphane concentration in broccoli and also tested whether there are concurrent effects on the concentration of ethanol, which is an unfavorable byproduct of fermentation. The sulforaphane concentration in broccoli florets was significantly elevated by 1.9- to 2.8-fold after 2 d of storage under hypoxia at ca. 0% O2 and ca. 24% CO2 at 20°C, whereas no such increase was observed following storage under normoxia at ca. 0% O2 without CO2 at 20°C. Furthermore, after 2 d, the sulforaphane concentration under hypoxia was 1.6- to 2.3-fold higher than that under normoxia. These results suggest that storage under hypoxia with high CO2 levels can elevate the sulforaphane concentration in broccoli florets. However, the elevated sulforaphane concentration could not be maintained beyond 2 d. There was no significant difference in the concentration of ethanol between florets that were stored under hypoxia with/without CO2 or normoxia at 2 d. However, the ethanol concentrations inside the pouches significantly increased between 2 d and 7 d. These findings indicate that the quality of broccoli florets can be improved through storage under hypoxia with high CO2 levels at 20°C for 2 d.

  16. Storage in high-barrier pouches increases the sulforaphane concentration in broccoli florets.

    Science.gov (United States)

    Makino, Yoshio; Nishimura, Yuto; Oshita, Seiichi; Mizosoe, Takaharu; Akihiro, Takashi

    2018-01-01

    Sulforaphane is a phytochemical that is usually found in cruciferous vegetables and is known to have a depressive effect on gastric cancer. Preliminary investigations showed that the sulforaphane concentration in broccoli (Brassica oleracea var. italica) florets increased under anoxia. Therefore, in the present study, we examined the effect of different atmospheric conditions on the sulforaphane concentration in broccoli and also tested whether there are concurrent effects on the concentration of ethanol, which is an unfavorable byproduct of fermentation. The sulforaphane concentration in broccoli florets was significantly elevated by 1.9- to 2.8-fold after 2 d of storage under hypoxia at ca. 0% O2 and ca. 24% CO2 at 20°C, whereas no such increase was observed following storage under normoxia at ca. 0% O2 without CO2 at 20°C. Furthermore, after 2 d, the sulforaphane concentration under hypoxia was 1.6- to 2.3-fold higher than that under normoxia. These results suggest that storage under hypoxia with high CO2 levels can elevate the sulforaphane concentration in broccoli florets. However, the elevated sulforaphane concentration could not be maintained beyond 2 d. There was no significant difference in the concentration of ethanol between florets that were stored under hypoxia with/without CO2 or normoxia at 2 d. However, the ethanol concentrations inside the pouches significantly increased between 2 d and 7 d. These findings indicate that the quality of broccoli florets can be improved through storage under hypoxia with high CO2 levels at 20°C for 2 d.

  17. Cation effect on small phosphonium based ionic liquid electrolytes with high concentrations of lithium salt

    Science.gov (United States)

    Chen, Fangfang; Kerr, Robert; Forsyth, Maria

    2018-05-01

    Ionic liquid electrolytes with high alkali salt concentrations have displayed some excellent electrochemical properties, thus opening up the field for further improvements to liquid electrolytes for lithium or sodium batteries. Fundamental computational investigations into these high concentration systems are required in order to gain a better understanding of these systems, yet they remain lacking. Small phosphonium-based ionic liquids with high concentrations of alkali metal ions have recently shown many promising results in experimental studies, thereby prompting us to conduct further theoretical exploration of these materials. Here, we conducted a molecular dynamics simulation on four small phosphonium-based ionic liquids with 50 mol. % LiFSI salt, focusing on the effect of cation structure on local structuring and ion diffusional and rotational dynamics—which are closely related to the electrochemical properties of these materials.

  18. High-dimensional orbital angular momentum entanglement concentration based on Laguerre–Gaussian mode selection

    International Nuclear Information System (INIS)

    Zhang, Wuhong; Su, Ming; Wu, Ziwen; Lu, Meng; Huang, Bingwei; Chen, Lixiang

    2013-01-01

    Twisted photons enable the definition of a Hilbert space beyond two dimensions by orbital angular momentum (OAM) eigenstates. Here we propose a feasible entanglement concentration experiment, to enhance the quality of high-dimensional entanglement shared by twisted photon pairs. Our approach is started from the full characterization of entangled spiral bandwidth, and is then based on the careful selection of the Laguerre–Gaussian (LG) modes with specific radial and azimuthal indices p and ℓ. In particular, we demonstrate the possibility of high-dimensional entanglement concentration residing in the OAM subspace of up to 21 dimensions. By means of LabVIEW simulations with spatial light modulators, we show that the Shannon dimensionality could be employed to quantify the quality of the present concentration. Our scheme holds promise in quantum information applications defined in high-dimensional Hilbert space. (letter)

  19. Protective effect of high concentrations of vitamin C on the radiation response of Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    O'Connor, M.K.; Malone, J.F.; Moriarty, M.

    1977-01-01

    The interaction of radiation with various chemical and physical agents has been studied with a view to finding safe reliable methods of altering radiosensitivity, as well as acquiring a deeper understanding of the chemical and physiological processes involved in the development of radiation damage. The agents most frequently studied include oxygen, known radiosensitisers, metabolic inhibitors and cytotoxic drugs. Because of toxicity, and related problems, manipulation of the concentrations of these substances in vivo is difficult. However many substances, whose importance in normal physiology is well established, have not been well studied from the point of view of their influence on radiation response. The influence of Vitamin C on the survival of mammalian cells (CHO - Clone A) after irradiation is reported. High concentrations of the vitamin (0.3 mg/ml) had a profound effect on radiosensitivity, giving a survival 7 times larger than untreated cells, at the highest dose used. Survival curves demonstrate that the effect is mainly, but not exclusively, due to an increase in the D 0 by a factor of about 1.5. The protective effect occurs in a concentration region that overlaps the physiological range, but the relationship between Vitamin C levels in the cells and in the medium, is complex. These observations could be of importance in reducing biological consequences of accidental radiation exposure, or deliberate diagnostic medical exposures. They may also be important in radiotherapy

  20. 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.

  1. An assessment of a spiral duct centrifuge using standard and high concentration aerosols

    International Nuclear Information System (INIS)

    Smith, A.D.

    1982-12-01

    The Stoeber spiral duct centrifuge has been calibrated by means of polystyrene latex microspheres for the subsequent measurement of aerosol particle size distributions. Intermediate (1 g m -3 ) ad high (100 g m -3 ) sodium chloride aerosol concentrations have been sampled by the centrifuge to determine possible limitations in the equipment. Corrections have to be made for the effect of Coriolis forces, and aerosol concentrations above 1 g m -3 should be diluted before sampling. The spiral duct centrifuge is an extremely versatile instrument for aerosol analysis, and shows a high degree of reliability when operated under well-defined conditions. (author)

  2. High surface hole concentration p-type GaN using Mg implantation

    CERN Document Server

    Long Tao; Zhang Guo Yi

    2001-01-01

    Mg ions were implanted on Mg-doped GaN grown by metalorganic chemical vapor deposition (MOCVD). The p-type GaN was achieved with high hole concentration (8.28 x 10 sup 1 sup 7 cm sup - sup 3) conformed by Van derpauw Hall measurement after annealing at 800 degree C for 1 h. this is the first experimental report of Mg implantation on Mg-doped GaN and achieving p-type GaN with high surface hole concentration

  3. 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.

  4. Separation and Concentration without Clogging Using a High-Throughput Tunable Filter

    Science.gov (United States)

    Mossige, E. J.; Jensen, A.; Mielnik, M. M.

    2018-05-01

    We present a detailed experimental study of a hydrodynamic filtration microchip and show how chip performance can be tuned and clogging avoided by adjusting the flow rates. We demonstrate concentration and separation of microspheres at throughputs as high as 29 ml /min and with 96% pureness. Results of streakline visualizations show that the thickness of a tunable filtration layer dictates the cutoff size and that two different concentration mechanisms exist. Particles larger than pores are concentrated by low-velocity rolling over the filtration pillars, while particles smaller than pores are concentrated by lateral drift across the filtration layer. Results of microscopic particle image velocimetry and particle-tracking velocimetry show that the degree of lateral migration can be quantified by the slip velocity between the particle and the surrounding fluid. Finally, by utilizing differences in inertia and separation mode, we demonstrate size-based separation of particles in a mixture.

  5. Optical performance evaluation of a solar furnace by measuring the highly concentrated solar flux

    International Nuclear Information System (INIS)

    Lee, Hyunjin; Chai, Kwankyo; Kim, Jongkyu; Lee, Sangnam; Yoon, Hwanki; Yu, Changkyun; Kang, Yongheack

    2014-01-01

    We evaluated optical performance of a solar furnace in the KIER (Korea Institute of Energy Research) by measuring the highly concentrated solar flux with the flux mapping method. We presented and analyzed optical performance in terms of concentrated solar flux distribution and power distribution. We investigated concentration ratio, stagnation temperature, total power, and concentration accuracy with help of a modeling code based on the ray tracing method and thereby compared with other solar furnaces. We also discussed flux changes by shutter opening angles and by position adjustment of reflector facets. In the course of flux analysis, we provided a better understanding of reference flux measurement for calibration, reflectivity measurement with a portable reflectometer, shadowing area consideration for effective irradiation, as well as accuracy and repeatability of flux measurements. The results in the present study will help proper utilization of a solar furnace by facilitating comparison between flux measurements at different conditions and flux estimation during operation

  6. PKU: high plasma phenylalanine concentrations are associated with increased prevalence of mood swings.

    Science.gov (United States)

    Anjema, Karen; van Rijn, Margreet; Verkerk, Paul H; Burgerhof, Johannes G M; Heiner-Fokkema, M Rebecca; van Spronsen, Francjan J

    2011-11-01

    In phenylketonuria, knowledge about the relation between behavior and plasma phenylalanine is scarce. The aim of this study was to determine whether high phenylalanine is associated with disturbed behavior noticed by the patient and or close environment (parents or partners). 48 early treated PKU patients (median age 8.5, range 0-35 years) participated (median phenylalanine concentration in total sample 277 (range 89-1171) μmol/l; and in patients introvert or extravert behavior. The interviewer as well as the respondents were blinded with regard to the phenylalanine concentration. Patients reported less deviant behavior compared to close environment. Mood swings were positively associated with phenylalanine concentrations in the total group (P=0.039) and patients introvert and extravert behavior were not statistically significant. there is a positive association between phenylalanine concentrations and mood swings. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. [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.

  8. 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.

  9. 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

  10. Enhanced Enzymatic Production of Cephalexin at High Substrate Concentration with in situ Product Removal by Complexation

    Directory of Open Access Journals (Sweden)

    Dengchao Li

    2008-01-01

    Full Text Available Cephalexin (CEX was synthesized with 7-amino-3-deacetoxycephalosporanic acid (7-ADCA and D(–-phenylglycine methyl ester (PGME using immobilized penicillin G acylase from Escherichia coli. It was found that substrate concentration and in situ product could remarkably influence the ratio of synthesis to hydrolysis (S/H and the efficiency of CEX synthesis. The optimal ratio of enzyme to substrate was 65 IU/mM 7-ADCA. High substrate concentration improved the 7-ADCA conversion from 61 to 81 % in the process without in situ product removal (ISPR, while in the synthetic process with ISPR, high substrate concentration increased the 7-ADCA conversion from 88 to 98 %. CEX was easily separated from CEX/β-naphthol complex and its purity and overall yield were 99 and 70 %, respectively.

  11. 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.

  12. 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.

  13. Niacin alters the ruminal microbial composition of cattle under high-concentrate condition

    Directory of Open Access Journals (Sweden)

    Dan Luo

    2017-06-01

    Full Text Available To understand the effects of niacin on the ruminal microbial ecology of cattle under high-concentrate diet condition, Illumina MiSeq sequencing technology was used. Three cattle with rumen cannula were used in a 3 × 3 Latin-square design trial. Three diets were fed to these cattle during 3 periods for 3 days, respectively: high-forage diet (HF; forage-to-concentrate ratio = 80:20, high-concentrate diet (HC; forage-to-concentrate ratio = 20:80, and HC supplemented with 800 mg/kg niacin (HCN. Ruminal pH was measured before feeding and every 2 h after initiating feeding. Ruminal fluid was sampled at the end of each period for microbial DNA extraction. Overall, our findings revealed that subacute ruminal acidosis (SARA was induced and the α-diversity of ruminal bacterial community decreased in the cattle of HC group. Adding niacin in HC could relieve the symptoms of SARA in the cattle but the ruminal pH value and the Shannon index of ruminal bacterial community of HCN group were still lower than those of HF group. Whatever the diet was, the ruminal bacterial community of cattle was dominated by Bacteroidetes, Firmicutes and Proteobacteria. High-concentrate diet significantly increased the abundance of Prevotella, and decreased the abundance of Paraprevotella, Sporobacter, Ruminococcus and Treponema than HF. Compared with HC, HCN had a trend to decrease the percentage of Prevotella, and to increase the abundance of Succiniclasticum, Acetivibrio and Treponema. Increasing concentrate ratio could decrease ruminal pH value, and change the ruminal microbial composition. Adding niacin in HC could increase the ruminal pH value, alter the ruminal microbial composition.

  14. Implications of Industrial Processing Strategy on Cellulosic Ethanol Production at High Solids Concentrations

    DEFF Research Database (Denmark)

    Cannella, David

    The production of cellulosic ethanol is a biochemical process of not edible biomasses which contain the cellulose. The process involves the use of enzymes to hydrolyze the cellulose in fermentable sugars to finally produce ethanol via fermentative microorganisms (i.e. yeasts). These biomasses...... are the leftover of agricultural productions (straws), not edible crops (giant reed) or wood, thus the ethanol so produced is also called second generation (or 2G ethanol), which differs from the first generation produced from starch (sugar beets mostly). In the industrial production of cellulosic ethanol high...... solids strategy resulted critical for its cost effectiveness: high concentration of initial biomass it will lead to high concentration of the final product (ethanol), thus more convenient to isolate. This thesis investigate the implementation of a high solids loading concept into cellulosic ethanol...

  15. 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.

  16. Analytical Study of High Concentration PCB Paint at the Heavy Water Components Test Reactor

    International Nuclear Information System (INIS)

    Lowry, N.J.

    1998-01-01

    This report provides results of an analytical study of high concentration PCB paint in a shutdown nuclear test reactor located at the US Department of Energy's Savannah River Site (SRS). The study was designed to obtain data relevant for an evaluation of potential hazards associated with the use of and exposure to such paints

  17. Analytical Study of High Concentration PCB Paint at the Heavy Water Components Test Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Lowry, N.J.

    1998-10-21

    This report provides results of an analytical study of high concentration PCB paint in a shutdown nuclear test reactor located at the US Department of Energy's Savannah River Site (SRS). The study was designed to obtain data relevant for an evaluation of potential hazards associated with the use of and exposure to such paints.

  18. Resting serum concentration of high-sensitivity C-reactive protein ...

    African Journals Online (AJOL)

    Resting serum concentration of high-sensitivity C-reactive protein (hs-CRP) in sportsmen and untrained male adults. F.A. Niyi-Odumosu, O. A. Bello, S.A. Biliaminu, B.V. Owoyele, T.O. Abu, O.L. Dominic ...

  19. The preparation and ethanol fermentation of high-concentration sugars from steam-explosion corn stover.

    Science.gov (United States)

    Xie, Hui; Wang, Fengqin; Yin, Shuangyao; Ren, Tianbao; Song, Andong

    2015-05-01

    In the field of biofuel ethanol, high-concentration- reducing sugars made from cellulosic materials lay the foundation for high-concentration ethanol fermentation. In this study, corn stover was pre-treated in a process combining chemical methods and steam explosion; the cellulosic hydrolyzed sugars obtained by fed-batch saccharification were then used as the carbon source for high-concentration ethanol fermentation. Saccharomyces cerevisiae 1308, Angel yeast, and Issatchenkia orientalis were shake-cultured with Pachysolen tannophilus P-01 for fermentation. Results implied that the ethanol yields from the three types of mixed strains were 4.85 g/100 mL, 4.57 g/100 mL, and 5.02 g/100 mL (separately) at yield rates of 91.6, 89.3, and 92.2%, respectively. Therefore, it was inferred that shock-fermentation using mixed strains achieved a higher ethanol yield at a greater rate in a shorter fermentation period. This study provided a theoretical basis and technical guidance for the fermentation of industrial high-concentrated cellulosic ethanol.

  20. Mapping the Life Satisfaction of Adolescents in Hong Kong Secondary Schools with High Ethnic Concentration

    Science.gov (United States)

    Yuen, Yuet Mui Celeste; Lee, Moosung

    2016-01-01

    The present study aims to map the life satisfaction of adolescents from ethnic minority/immigrant backgrounds in schools with high concentrations of co-ethnic peers by comparing them with their mainstream counterparts in Hong Kong. The life satisfaction of 1,522 students was measured by the validated Multidimensional Students' Life Satisfaction…

  1. Production of ethanol from wheat straw by pretreatment and fermentation at high dry matter concentrations

    NARCIS (Netherlands)

    Groenestijn, J.W. van; Slomp, R.S.

    2011-01-01

    High concentrations of substrate and product are important for the economy of second-generation bioethanol production. By a dilute acid thermal pretreatment of large pieces of relatively dry wheat straw using a novel rapid heating method, followed by fed-batch preliquefaction with hydrolytic

  2. Decadal and seasonal trends of nutrient concentration and export from highly managed coastal catchments.

    Science.gov (United States)

    Wan, Yongshan; Wan, Lei; Li, Yuncong; Doering, Peter

    2017-05-15

    Understanding anthropogenic and hydro-climatic influences on nutrient concentrations and export from highly managed catchments often necessitates trend detection using long-term monitoring data. This study analyzed the temporal trend (1979-2014) of total nitrogen (TN) and total phosphorus (TP) concentrations and export from four adjacent coastal basins in south Florida where land and water resources are highly managed through an intricate canal network. The method of integrated seasonal-trend decomposition using LOESS (LOcally weighted regrESSion) was employed for trend detection. The results indicated that long-term trends in TN and TP concentrations (increasing/decreasing) varied with basins and nutrient species, reflecting the influence of basin specific land and water management practices. These long-term trends were intervened by short-term highs driven by high rainfall and discharges and lows associated with regional droughts. Seasonal variations in TP were more apparent than for TN. Nutrient export exhibited a chemostatic behavior for TN from all the basins, largely due to the biogenic nature of organic N associated with the ubiquity of organic materials in the managed canal network. Varying degrees of chemodynamic export was present for TP, reflecting complex biogeochemical responses to the legacy of long-term fertilization, low soil P holding capacity, and intensive stormwater management. The anthropogenic and hydro-climatic influences on nutrient concentration and export behavior had great implications in nutrient loading abatement strategies for aquatic ecosystem restoration of the downstream receiving waterbody. Published by Elsevier Ltd.

  3. Innovative encapsulated oxygen-releasing beads for bioremediation of BTEX at high concentration in groundwater.

    Science.gov (United States)

    Lin, Chi-Wen; Wu, Chih-Hung; Guo, Pei-Yu; Chang, Shih-Hsien

    2017-12-15

    Both a low concentration of dissolved oxygen and the toxicity of a high concentration of BTEX inhibit the bioremediation of BTEX in groundwater. A novel method of preparing encapsulated oxygen-releasing beads (encap-ORBs) for the biodegradation of BTEX in groundwater was developed. Experimental results show that the integrality and oxygen-releasing capacity of encap-ORBs exceeded those of ORBs. The use of polyvinyl alcohol (PVA) with high M.W. to prepare encap-ORBs improved their integrality. The encap-ORBs effectively released oxygen for 128 days. High concentration of BTEX (480 mg L -1 ) inhibited the biodegradation by the free cells. Immobilization of degraders in the encap-ORB alleviated the inhibition. Scanning electron microscope analysis reveals that the BTEX degraders grew on the surface of encap-ORB after bioremediation. The above results indicate that the encap-ORBs were effective in the bioremediation of BTEX at high concentration in groundwater. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Comparison of direct sampling and brochoalveolar lavage for determining active drug concentrations in the pulmonary epithelial lining fluid of calves injected with enrofloxacin or tilmicosin.

    Science.gov (United States)

    Foster, D M; Sylvester, H J; Papich, M G

    2017-12-01

    Antibiotic distribution to interstitial fluid (ISF) and pulmonary epithelial fluid (PELF) was measured and compared to plasma drug concentrations in eight healthy calves. Enrofloxacin (Baytril ® 100) was administered at a dose of 12.5 mg/kg subcutaneously (SC), and tilmicosin (Micotil ® 300) was administered at a dose of 20 mg/kg SC. PELF, sampled by two different methods-bronchoalveolar lavage (BAL) and direct sampling (DS)-plasma, and ISF were collected from each calf and measured for tilmicosin, enrofloxacin and its metabolite ciprofloxacin by HPLC. Pharmacokinetic analysis was performed on the concentrations in each fluid, for each drug. The enrofloxacin/ciprofloxacin concentration as measured by AUC in DS samples was 137 ± 72% higher than in plasma, but in BAL samples, this value was 535 ± 403% (p enrofloxacin/ciprofloxacin concentrations collected by DS were significantly different than those collected by BAL, but the tilmicosin concentrations were not significantly different between the two methods. Concentrations of enrofloxacin/ciprofloxacin exceeded the MIC values for bovine respiratory disease pathogens but tilmicosin did not reach MIC levels for these pathogens in any fluids. © 2017 John Wiley & Sons Ltd.

  5. 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.

  6. Quality of care and patient satisfaction in hospitals with high concentrations of black patients.

    Science.gov (United States)

    Brooks-Carthon, J Margo; Kutney-Lee, Ann; Sloane, Douglas M; Cimiotti, Jeannie P; Aiken, Linda H

    2011-09-01

    To examine the influence of nursing-specifically nurse staffing and the nurse work environment-on quality of care and patient satisfaction in hospitals with varying concentrations of Black patients. Cross-sectional secondary analysis of 2006-2007 nurse survey data collected across four states (Florida, Pennsylvania, New Jersey, and California), the Hospital Consumer Assessment of Healthcare Providers and Systems survey, and administrative data. Global analysis of variance and linear regression models were used to examine the association between the concentration of Black patients on quality measures (readiness for discharge, patient or family complaints, health care-associated infections) and patient satisfaction, before and after accounting for nursing and hospital characteristics. Nurses working in hospitals with higher concentrations of Blacks reported poorer confidence in patients' readiness for discharge and more frequent complaints and infections. Patients treated in hospitals with higher concentrations of Blacks were less satisfied with their care. In the fully adjusted regression models for quality and patient satisfaction outcomes, the effects associated with the concentration of Blacks were explained in part by nursing and structural hospital characteristics. This study demonstrates a relationship between nursing, structural hospital characteristics, quality of care, and patient satisfaction in hospitals with high concentrations of Black patients. Consideration of nursing factors, in addition to other important hospital characteristics, is critical to understanding and improving quality of care and patient satisfaction in minority-serving hospitals. © 2011 Sigma Theta Tau International.

  7. High concentrations of thiosulfate in scala tympani perilymph after systemic administration in the guinea pig.

    Science.gov (United States)

    Pierre, Pernilla Videhult; Engmér, Cecilia; Wallin, Inger; Laurell, Göran; Ehrsson, Hans

    2009-02-01

    High concentrations of the antioxidant thiosulfate reach scala tympani perilymph after i.v. administration in the guinea pig. Thiosulfate concentrations in perilymph remain elevated longer than in blood. This warrants further studies on the possibility of obtaining otoprotection by thiosulfate administration several hours before that of cisplatin without compromising the anticancer effect caused by cisplatin inactivation in the blood compartment. Thiosulfate may reduce cisplatin-induced ototoxicity, presumably by oxidative stress relief and formation of inactivate platinum complexes. This study aimed to explore to what extent thiosulfate reaches scala tympani perilymph after systemic administration in the guinea pig. Scala tympani perilymph (1 microl) was aspirated from the basal turn of each cochlea up to 3 h after thiosulfate administration (103 mg/kg b.w., i.v.). Blood samples were also taken. Thiosulfate was quantified by HPLC and fluorescence detection. Substantial thiosulfate concentrations were found in perilymph. The area under the concentration-time curve for thiosulfate in perilymph and blood was 3100 microMxmin and 6300 microMxmin, respectively. The highest thiosulfate concentrations in perilymph were found at the first sampling at about 10 min. Due to a more rapid elimination from blood, perilymph concentrations exceeded those of blood towards the end of the experiment.

  8. Concentration-Induced Association in a Protein System Caused by a Highly Directional Patch Attraction.

    Science.gov (United States)

    Li, Weimin; Persson, Björn A; Lund, Mikael; Bergenholtz, Johan; Zackrisson Oskolkova, Malin

    2016-09-01

    Self-association of the protein lactoferrin is studied in solution using small-angle X-ray scattering techniques. Effective static structure factors have been shown to exhibit either a monotonic or a nonmonotonic dependence on protein concentration in the small wavevector limit, depending on salt concentration. The behavior correlates with a nonmonotonic dependence of the second virial coefficient on salt concentration, such that a maximum appears in the structure factor at a low protein concentration when the second virial coefficient is negative and close to a minimum. The results are interpreted in terms of an integral equation theory with explicit dimers, formulated by Wertheim, which provides a consistent framework able to explain the behavior in terms of a monomer-dimer equilibrium that appears because of a highly directional patch attraction. Short attraction ranges preclude trimer formation, which explains why the protein system behaves as if it were subject to a concentration-dependent isotropic protein-protein attraction. Superimposing an isotropic interaction, comprising screened Coulomb repulsion and van der Waals attraction, on the patch attraction allows for a semiquantitative modeling of the complete transition pathway from monomers in the dilute limit to monomer-dimer systems at somewhat higher protein concentrations.

  9. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

    Directory of Open Access Journals (Sweden)

    Béatrice Marquèze-Pouey

    Full Text Available Signaling mediated by the epidermal growth factor (EGF is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer. In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

  10. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

    Science.gov (United States)

    Marquèze-Pouey, Béatrice; Mailfert, Sébastien; Rouger, Vincent; Goaillard, Jean-Marc; Marguet, Didier

    2014-01-01

    Signaling mediated by the epidermal growth factor (EGF) is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer). In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar) concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

  11. Investigation on the effect of thermal resistances on a highly concentrated photovoltaic-thermoelectric hybrid system

    International Nuclear Information System (INIS)

    Zhang, Jin; Xuan, Yimin

    2016-01-01

    Highlights: • The highly concentrated PV-TE hybrid system is studied. • The performances of different cooling systems are analyzed and compared. • Sandwiching a copper plate between the PV and TE can improve the efficiency. • Four thermal design principles of the system are proposed. - Abstract: A thermal analysis of a highly concentrated photovoltaic-thermoelectric (PV-TE) hybrid system is carried out in this paper. Both the output power and the temperature distribution in the hybrid system are calculated by means of a three-dimensional numerical model. Three possible approaches for designing the highly concentrated PV-TE hybrid system are presented by analyzing the thermal resistance of the whole system. First, the sensitivity analysis shows that the thermal resistance between the TE module and the environment has a more great effect on the output power than the thermal resistance between the PV and the TE. The influence of the natural convection and the radiation can be ignored for the highly concentrated PV-TE hybrid system. Second, it is necessary to sandwich a copper plate between the PV and the TE for decreasing the thermal resistance between the PV and the TE. The role of the copper plate is to improve the temperature uniformity. Third, decreasing the area of PV cells can improve the efficiency of the highly concentrated PV-TE hybrid system. It should be pointed out that decreasing the area of PV cells also increases the total thermal resistance, but the raise of the efficiency is caused by the reduction of the heat transfer rate of the system. Therefore, the principle of minimizing the total thermal resistance may not be suitable for optimizing the area of PV cells.

  12. 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.

  13. 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.

  14. Competing pathways in drug metabolism. I. Effect of input concentration on the conjugation of gentisamide in the once-through in situ perfused rat liver preparation

    International Nuclear Information System (INIS)

    Morris, M.E.; Yuen, V.; Tang, B.K.; Pang, K.S.

    1988-01-01

    Sulfation and glucuronidation are two parallel pathways for the metabolism of phenolic substrates. Gentisamide (GAM) was used as a model compound to examine the effects of parallel competing pathways on drug disappearance and metabolite formation in the once-through perfused rat liver preparation. GAM was found to form one glucuronide (GAM-5G) and two sulfate (GAM-2S and GAM-5S) conjugates. These GAM conjugates were biosynthesized in recirculating rat liver preparations, and were isolated by preparative high-performance liquid chromatography. Specific incorporation of 35S-sodium sulfate and [14C]glucose into GAM sulfate and glucuronide conjugates revealed corresponding elution patterns as labeled GAM metabolites. Their identities were characterized by enzymatic and acid hydrolyses and by NMR spectroscopy. Gentisamide-5-sulfate (GAM-5S) and gentisamide-5-glucuronide (GAM-5G) are major metabolites, and gentisamide-2-sulfate (GAM-2S) is a minor metabolite. Single-pass rat liver perfusions were used to examine the effect of stepwise increases/decreases of input GAM concentration (CIn) on the extraction ratio (E) of GAM and formation of metabolites. The E of GAM remained constant (about 0.89) at input concentrations from 0.9 to 120 microM and decreased at CIn greater than 120 microM. Metabolite patterns, however, changed with GAM CIn, even when E was constant at CIn up to 120 microM. GAM-5S was present as the major metabolite of GAM at all GAM CInS in most liver preparations but the proportions of GAM-5S and GAM-2S decreased at increasing CIn; the proportion of GAM-5G, a minor metabolite at low CIn, increased with increasing CIn. Biliary excretion rates at steady state accounted for 5.3 +/- 2.7% (mean +/- S.D.) of the input rate: GAM-5G was the predominant metabolite found

  15. Influence of vibration on structure rheological properties of a highly concentrated suspension

    Science.gov (United States)

    Ouriev Uriev, Boris N.; Uriev, Naum B.

    2005-08-01

    The influence of mechanical vibration on the flow properties of a highly concentrated multiphase food system is explored in this work. An experimental set-up was designed and adapted to a conventional rotational rheometer with precise rheological characterization capability. A number of calibration tests were performed prior to fundamental experiments with a highly concentrated chocolate suspension. Also, the prediction of wall slippage in shear flow under vibration was evaluated. Analysis of the boundary conditions shows that no side effects such as wall slippage or the Taylor effect were present during the shear experiment under vibration. It was found that superposition of mechanical vibration and shear flow radically decreases the shear viscosity. Comparison between reference shear viscosities at specified shear rates and those measured under vibration shows considerable differences in flow properties. Conversion of the behaviour of the concentrated suspension from strongly shear-thinning to Newtonian flow is reported. Also, the appearance of vibration-induced dilatancy as a new phenomenon is described. It is suggested to relate such phenomena to the non-equilibrium between structure formation and disintegration under vibration and hydrodynamic forces of shear flow. The influence of vibration on structure formation can be well observed during measurement of the yield value of the chocolate suspension under vibration. Comparison with reference data shows how sensitive the structure of the concentrated suspension is to vibration in general. The effects and observations revealed provide a solid basis for further fundamental investigations of structure formation regularities in the flow of any highly concentrated system. The results also show the technological potential for non-conventional treatment of concentrated, multiphase systems.

  16. Plasma PCSK9 concentrations during an oral fat load and after short term high-fat, high-fat high-protein and high-fructose diets

    Directory of Open Access Journals (Sweden)

    Cariou Bertrand

    2013-01-01

    Full Text Available Abstract Background PCSK9 (Proprotein Convertase Subtilisin Kexin type 9 is a circulating protein that promotes hypercholesterolemia by decreasing hepatic LDL receptor protein. Under non interventional conditions, its expression is driven by sterol response element binding protein 2 (SREBP2 and follows a diurnal rhythm synchronous with cholesterol synthesis. Plasma PCSK9 is associated to LDL-C and to a lesser extent plasma triglycerides and insulin resistance. We aimed to verify the effect on plasma PCSK9 concentrations of dietary interventions that affect these parameters. Methods We performed nutritional interventions in young healthy male volunteers and offspring of type 2 diabetic (OffT2D patients that are more prone to develop insulin resistance, including: i acute post-prandial hyperlipidemic challenge (n=10, ii 4 days of high-fat (HF or high-fat/high-protein (HFHP (n=10, iii 7 (HFruc1, n=16 or 6 (HFruc2, n=9 days of hypercaloric high-fructose diets. An acute oral fat load was also performed in two patients bearing the R104C-V114A loss-of-function (LOF PCSK9 mutation. Plasma PCSK9 concentrations were measured by ELISA. For the HFruc1 study, intrahepatocellular (IHCL and intramyocellular lipids were measured by 1H magnetic resonance spectroscopy. Hepatic and whole-body insulin sensitivity was assessed with a two-step hyperinsulinemic-euglycemic clamp (0.3 and 1.0 mU.kg-1.min-1. Findings HF and HFHP short-term diets, as well as an acute hyperlipidemic oral load, did not significantly change PCSK9 concentrations. In addition, post-prandial plasma triglyceride excursion was not altered in two carriers of PCSK9 LOF mutation compared with non carriers. In contrast, hypercaloric 7-day HFruc1 diet increased plasma PCSK9 concentrations by 28% (p=0.05 in healthy volunteers and by 34% (p=0.001 in OffT2D patients. In another independent study, 6-day HFruc2 diet increased plasma PCSK9 levels by 93% (p Conclusions Plasma PCSK9 concentrations vary

  17. Design and Optimization of Fresnel Lens for High Concentration Photovoltaic System

    Directory of Open Access Journals (Sweden)

    Lei Jing

    2014-01-01

    Full Text Available A practical optimization design is proposed, in which the solar direct light spectrum and multijunction cell response range are taken into account in combination, particularly for the Fresnel concentrators with a high concentration and a small aspect ratio. In addition, the change of refractive index due to temperature variation in outdoor operation conditions is also considered in the design stage. The calculation results show that this novel Fresnel lens achieves an enhancement of energy efficiency of about 10% compared with conventional Fresnel lens for a given solar spectrum, solar cell response, and corrected sunshine hours of different ambient temperature intervals.

  18. Enhanced Cycling Stability of Rechargeable Li-O2 Batteries Using High Concentration Electrolytes

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Bin; Xu, Wu; Yan, Pengfei; Sun, Xiuliang; Bowden, Mark E.; Read, Jeffrey; Qian, Jiangfeng; Mei, Donghai; Wang, Chong M.; Zhang, Jiguang

    2016-01-26

    The electrolyte stability against reactive reduced-oxygen species is crucial for the development of rechargeable Li-O2 batteries. In this work, we systematically investigated the effect of lithium salt concentration in 1,2-dimethoxyethane (DME)-based electrolytes on the cycling stability of Li-O2 batteries. Cells with high concentration electrolyte illustrate largely enhanced cycling stability under both the full discharge/charge (2.0-4.5 V vs. Li/Li+) and the capacity limited (at 1,000 mAh g-1) conditions. These cells also exhibit much less reaction-residual on the charged air electrode surface, and much less corrosion to the Li metal anode. The density functional theory calculations are conducted on the molecular orbital energies of the electrolyte components and the Gibbs activation barriers for superoxide radical anion to attack DME solvent and Li+-(DME)n solvates. In a highly concentrated electrolyte, all DME molecules have been coordinated with salt and the C-H bond scission of a DME molecule becomes more difficult. Therefore, the decomposition of highly concentrated electrolyte in a Li-O2 battery can be mitigated and both air-cathodes and Li-metal anodes exhibits much better reversibility. As a results, the cyclability of Li-O2 can be largely improved.

  19. Spectral and Concentration Sensitivity of Multijunction Solar Cells at High Temperature: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, Daniel J.; Steiner, Myles A.; Perl, Emmett E.; Simon, John

    2017-06-14

    We model the performance of two-junction solar cells at very high temperatures of ~400 degrees C and beyond for applications such as hybrid PV/solar-thermal power production, and identify areas in which the design and performance characteristics behave significantly differently than at more conventional near-room-temperature operating conditions. We show that high-temperature operation reduces the sensitivity of the cell efficiency to spectral content, but increases the sensitivity to concentration, both of which have implications for energy yield in terrestrial PV applications. For other high-temperature applications such as near-sun space missions, our findings indicate that concentration may be a useful tool to enhance cell efficiency.

  20. Influence of a High-Pressure Comminution Technology on Concentrate Yields in Copper Ore Flotation Processes

    Directory of Open Access Journals (Sweden)

    Saramak D.

    2014-10-01

    Full Text Available The article concerns the issues of flotation process effectiveness in relationship to the operating conditions of a high-pressure comminution process course. Experimental programme covering a flotation laboratory batch tests was a verification technique of a high-pressure crushing operations course. The most favorable values of flotation concentrate weight recoveries were obtained for the pressing force 6 kN and 4% of the feed moisture. It was also determined the model of the concentrate weight recovery as a function of pressing force in the press and feed moisture content. This model was the basis for the optimization of effects of copper ore flotation processes preceded in high-pressure crushing operation in roller presses.

  1. The role of silicon interstitials in the deactivation and reactivation of high concentration boron profiles

    Energy Technology Data Exchange (ETDEWEB)

    Aboy, Maria [Campus Miguel Delibes, University of Valladolid, 47011 Valladolid (Spain)]. E-mail: marabo@tel.uva.es; Pelaz, Lourdes [Campus Miguel Delibes, University of Valladolid, 47011 Valladolid (Spain); Marques, Luis A. [Campus Miguel Delibes, University of Valladolid, 47011 Valladolid (Spain); Lopez, Pedro [Campus Miguel Delibes, University of Valladolid, 47011 Valladolid (Spain); Barbolla, Juan [Campus Miguel Delibes, University of Valladolid, 47011 Valladolid (Spain); Venezia, V.C. [Philips Research Leuven, Leuven (Belgium); Duffy, R. [Philips Research Leuven, Leuven (Belgium); Griffin, Peter B. [Stanford University, Stanford, CA (United States)

    2004-12-15

    Boron cluster formation and dissolution in high concentration B profiles and the role of Si interstitials in these processes are analyzed by kinetic non-lattice Monte Carlo atomistic simulations. For this purpose, we use theoretical structures as simplifications of boron implants into preamorphized Si, followed by low-temperature solid phase epitaxial (SPE) regrowth or laser thermal annealing process. We observe that in the presence of high B concentrations (above 10{sup 20} cm{sup -3}), significant deactivation occurs during high temperature anneal, even in the presence of only equilibrium Si interstitials. The presence of additional Si interstitials from an end of range (EOR) damage region accelerates the deactivation process and makes B deactivation slightly higher. We show that B deactivation and reactivation processes can be clearly correlated to the evolution of Si interstitial defects at the EOR. The minimum level of activation occurs when the Si interstitial defects at EOR dissolve or form very stable defects.

  2. Phenomenon of energy concentration in super-high energy γ-hadron families

    International Nuclear Information System (INIS)

    Dai Zhiqiang; Xue Liang; Li Jinyu; Zhang Xueyao; Feng Cunfeng; Fu Yu; Li Jie; Cao Peiyuan; Zhang Naijian; He Mao; Wang Chengrui; Ren Jingru; Lu Suiling

    2000-01-01

    The family events observed with iron emulsion chambers at Mt. Kanbala are analyzed and compared with the simulations by the COSMOS code and CORSIKA code respectively. A detailed study on the production of super-high energy γ-hadron families with energy concentration behavior is carried out. The preliminary conclusions are: 1) the energy concentration behavior of super-high energy γ-hadron families is the external embodiment of high energy central shower clusters contained in the families. 2) the mean lateral spread of these clusters is about 0.37 cm. 3) the frequency of this phenomenon appeared under the conditions of R≤10 mm and X 10 ≥90% is (20.5 +- 3.1)%. 4) compared to the COSMOS code based on the phenomenological multi-cluster model, the simulation by the CORSIKA code that adopts SIBYLL model is closer to the analytical results of experiment

  3. High concentrations of H2O2 make aerobic glycolysis energetically more favourable than cellular respiration.

    Directory of Open Access Journals (Sweden)

    Hamid R Molavian

    2016-08-01

    Full Text Available Since the original observation of the Warburg Effect in cancer cells, over eight decades ago, the major question of why aerobic glycolysis is favored over oxidative phosphorylation has remained unresolved. An understanding of this phenomenon may well be the key to the development of more effective cancer therapies. In this paper, we use a semi-empirical method to throw light on this puzzle. We show that aerobic glycolysis is in fact energetically more favorable than oxidative phosphorylation for concentrations of peroxide (H2O2 above some critical threshold value. The fundamental reason for this is the activation and high engagement of the pentose phosphate pathway (PPP in response to the production of reactive oxygen species H2O2 by mitochondria and the high concentration of H2O2 (produced by mitochondria and other sources. This makes oxidative phosphorylation an inefficient source of energy since it leads (despite high levels of ATP production to a concomitant high energy consumption in order to respond to the hazardous waste products resulting from cellular processes associated with this metabolic pathway. We also demonstrate that the high concentration of H2O2 results in an increased glucose consumption, and also increases the lactate production in the case of glycolysis.

  4. Quality evaluation of moluodan concentrated pill using high-performance liquid chromatography fingerprinting coupled with chemometrics.

    Science.gov (United States)

    Tao, Lingyan; Zhang, Qing; Wu, Yongjiang; Liu, Xuesong

    2016-12-01

    In this study, a fast and effective high-performance liquid chromatography method was developed to obtain a fingerprint chromatogram and quantitative analysis simultaneously of four indexes including gallic acid, chlorogenic acid, albiflorin and paeoniflorin of the traditional Chinese medicine Moluodan Concentrated Pill. The method was performed by using a Waters X-bridge C 18 reversed phase column on an Agilent 1200S high-performance liquid chromatography system coupled with diode array detection. The mobile phase of the high-performance liquid chromatography method was composed of 20 mmol/L phosphate solution and acetonitrile with a 1 mL/min eluent velocity, under a detection temperature of 30°C and a UV detection wavelength of 254 nm. After the methodology validation, 16 batches of Moluodan Concentrated Pill were analyzed by this high-performance liquid chromatography method and both qualitative and quantitative evaluation results were achieved by similarity analysis, principal component analysis and hierarchical cluster analysis. The results of these three chemometrics were in good agreement and all indicated that batch 10 and batch 16 showed significant differences with the other 14 batches. This suggested that the developed high-performance liquid chromatography method could be applied in the quality evaluation of Moluodan Concentrated Pill. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

    Energy Technology Data Exchange (ETDEWEB)

    Montes, Daniela K.; Brenet, Marianne; Muñoz, Vanessa C.; Burgos, Patricia V.; Villanueva, Carolina I. [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); González, Carlos B., E-mail: cbgonzal@uach.cl [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2013-11-29

    Highlights: •AVP induces mTOR phosphorylation in A-10 cells cultured in high glucose concentration. •The mTOR phosphorylation is mediated by the PI3K/Akt pathway activation. •The AVP-induced mTOR phosphorylation inhibited autophagy and stimulated cell proliferation. -- Abstract: Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

  6. 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.

  7. 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

  8. 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.

  9. Development of postcompressional textural tests to evaluate the mechanical properties of medicated chewing gum tablets with high drug loadings.

    Science.gov (United States)

    Al Hagbani, Turki; Nazzal, Sami

    2018-02-01

    Medicated chewing gum tablets (CGTs) represent a unique platform for drug delivery. Loading directly compressible gums with high concentrations of powdered medication, however, results in compacts with hybrid properties between a chewable gum and a brittle tablet. The aim of the present study was to develop textural tests that can identify the point at which CGTs begin to behave like a solid tablet upon drug incorporation. Curcumin (CUR) CGTs made with Health in gum were prepared with increasing CUR load from 0 to 100% and were characterized for their mechanical properties by a single-bite (knife) and a two-bite tests. From each test several parameters were extracted and correlated with drug loading. In the single-bite test, the change in the resistance of the compacts to plastic deformation was found to give a definitive guide on whether they behave as gums or tablets. A more in depth analysis of the impact of CUR loading on the chewability of the CGTs was provided by the two-bite test where CUR loading was found to have a nonlinear impact on the mechanical properties of compacts. An upper limit of 10% was found to yield compacts with gum-like properties, which were abolished at higher CUR loads. The textural test procedure outlined in this study are expected to assist those involved in the formulation of medicated gums for pharmaceutical applications in making an informed decision on the impact of drug loading on gum behavior before proceeding with clinical testing. There is a growing interest in utilizing medicated chewing gums for drug delivery, especially those made using directly compressible gum bases, such as Health in gum. Directly compressing a gum base with high amounts of solid drug powder, however, poses a challenge as it may result in compressed compacts with hybrid properties between a chewing gum and a hard tablet. Currently, official Pharmacopeias do not specify a testing procedure for the estimation of the mechanical and textural properties of

  10. 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…

  11. Circulating adiponectin concentration and body composition are altered in response to high-intensity interval training.

    Science.gov (United States)

    Shing, Cecilia M; Webb, Jessica J; Driller, Matthew W; Williams, Andrew D; Fell, James W

    2013-08-01

    Adiponectin influences metabolic adaptations that would prove beneficial to endurance athletes, and yet to date there is little known about the response of adiponectin concentrations to exercise, and, in particular, the response of this hormone to training in an athlete population. This study aimed to determine the response of plasma adiponectin concentrations to acute exercise after 2 different training programs and to determine the influence of the training on body composition. Seven state-level representative rowers (age: 19 ± 1.2 years [mean ± SD], height: 1.77 ± 0.10 m, body mass: 74.0 ± 10.7 kg, VO2peak 62.1 ± 7.0 ml·kg·min) participated in the double-blind, randomized crossover investigation. Rowers performed an incremental graded exercise test before and after completing 4 weeks of high-intensity interval ergometer training and 4 weeks of traditional ergometer rowing training. Rowers' body composition was assessed at baseline and after each training program. Significant increases in plasma adiponectin concentration occurred in response to maximal exercise after completion of the high-intensity interval training (p = 0.016) but not after traditional ergometer rowing training (p = 0.69). The high-intensity interval training also resulted in significant increases in mean 4-minute power output (p = 0.002) and VO2peak (p = 0.05), and a decrease in body fat percentage (p = 0.022). Mean 4-minute power output, VO2peak, and body fat percentage were not significantly different after 4 weeks of traditional ergometer rowing training (p > 0.05). Four weeks of high-intensity interval training is associated with an increase in adiponectin concentration in response to maximal exercise and a reduction in body fat percentage. The potential for changes in adiponectin concentration to reflect positive training adaptations and athlete performance level should be further explored.

  12. 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.

  13. Inhibition of raw starch digestion by one glucoamylase preparation from black Aspergillus at high enzyme concentration

    Energy Technology Data Exchange (ETDEWEB)

    Saka, B C; Veda, S

    1981-09-01

    Raw starch digestion by glucoamylase I (Ab. G-I) preparation from black Aspergillus was inhibited significantly at relatively high concentration of the enzyme. The properties of this enzyme were studied together with those of another glucoamylase I (Nor. G-I), also from black Aspergillus. The two glucoamylases do not differ so much in their physico-chemical properties such as molecular weight, pH and thermal stability, pH and temperature optimum, substrate specificity, debranching activity, isoelectric point etc. The adsorption rate of both enzymes on raw starch increased by the increase of enzyme concentration. The raw starch digestion rate by adsorbed Ab. G-I, however, was decreased with the increase of concentration of enzyme whereas the same was increased in case of Nor. G-I. The inhibitory effect was weaker at 60 deg. Celcius or above. (Refs. 11).

  14. Advanced Oxidation Processes (AOPs for Refinery Wastewater Treatment Contains High Phenol Concentration

    Directory of Open Access Journals (Sweden)

    Azizah Alif Nurul

    2018-01-01

    Full Text Available Petroleum Refinery wastewater is characterized by a high phenol content. Phenol is toxic and resistant to biological processes for treatment of the petroleum refinery wastewater. The combination of an AOP and a biological process can be used for treatment of the refinery wastewater. It is necessary to conduct a study to determine the appropriate condition of AOP to meet the phenol removal level. Two AOP configurations were investigated: H2O2 / UV and H2O2 / UV / O3. From each process samples, COD, phenol and pH were measured. The oxidation was carried out until the targeted phenol concentration of treated effluent were obtained. The better result obtained by using process H2O2 / UV / O3 with the H2O2 concentration 1000 ppm. After 120 minutes, the final target has been achieved in which phenol concentration of 37.5 mg/L or phenol degradation of 93.75%.

  15. Diffusion of ion-implanted B in high concentration P- and As-doped silicon

    International Nuclear Information System (INIS)

    Fair, R.B.; Pappas, P.N.

    1975-01-01

    The diffusion of ion-implanted B in Si in the presence of a uniform background of high concentration P or As was studied by correlating numerical profile calculations with profiles determined by secondary-ion mass spectrometry (SIMS). Retarded B diffusion is observed in both As- and P-doped Si, consistent with the effect of the local Fermi-level position in the Si band gap on B diffusivity, D/sub B/. It is shown that D/sub B/ is linearly dependent on the free hole concentration, p, over the range 0.1 less than p/n/sub ie/ less than 30, where n/sub ie/ is the effective intrinsic electron concentration. This result does not depend on the way in which the background dopant has been introduced (implantation predeposition or doped-oxide source), nor the type of dopant used (P or As). (U.S.)

  16. Effect of Temperature on Chinese Rice Wine Brewing with High Concentration Presteamed Whole Sticky Rice

    Directory of Open Access Journals (Sweden)

    Dengfeng Liu

    2014-01-01

    Full Text Available Production of high quality Chinese rice wine largely depends on fermentation temperature. However, there is no report on the ethanol, sugars, and acids kinetics in the fermentation mash of Chinese rice wine treated at various temperatures. The effects of fermentation temperatures on Chinese rice wine quality were investigated. The compositions and concentrations of ethanol, sugars, glycerol, and organic acids in the mash of Chinese rice wine samples were determined by HPLC method. The highest ethanol concentration and the highest glycerol concentration both were attained at the fermentation mash treated at 23°C. The highest peak value of maltose (90 g/L was obtained at 18°C. Lactic acid and acetic acid both achieved maximum values at 33°C. The experimental results indicated that temperature contributed significantly to the ethanol production, acid flavor contents, and sugar contents in the fermentation broth of the Chinese rice wines.

  17. Effect of Temperature on Chinese Rice Wine Brewing with High Concentration Presteamed Whole Sticky Rice

    Science.gov (United States)

    Zhang, Hong-Tao; Xiong, Weili; Hu, Jianhua; Xu, Baoguo; Lin, Chi-Chung; Xu, Ling; Jiang, Lihua

    2014-01-01

    Production of high quality Chinese rice wine largely depends on fermentation temperature. However, there is no report on the ethanol, sugars, and acids kinetics in the fermentation mash of Chinese rice wine treated at various temperatures. The effects of fermentation temperatures on Chinese rice wine quality were investigated. The compositions and concentrations of ethanol, sugars, glycerol, and organic acids in the mash of Chinese rice wine samples were determined by HPLC method. The highest ethanol concentration and the highest glycerol concentration both were attained at the fermentation mash treated at 23°C. The highest peak value of maltose (90 g/L) was obtained at 18°C. Lactic acid and acetic acid both achieved maximum values at 33°C. The experimental results indicated that temperature contributed significantly to the ethanol production, acid flavor contents, and sugar contents in the fermentation broth of the Chinese rice wines. PMID:24672788

  18. Analysis of drugs of abuse in human plasma by dispersive liquid-liquid microextraction and high-performance liquid chromatography.

    Science.gov (United States)

    Fernández, P; Regenjo, M; Bermejo, A M; Fernández, A M; Lorenzo, R A; Carro, A M

    2015-04-01

    Opioids and cocaine are widely used at present, both for recreational purposes and as drugs of abuse. This raises the need to develop new analytical methods specifically designed for the simultaneous detection of several drugs of abuse in biological samples. In this work, dispersive liquid-liquid microextraction (DLLME) was assessed as a new sample treatment for the simultaneous extraction of morphine (MOR), 6-acetylmorphine (6AM), cocaine (COC), benzoylecgonine (BZE) and methadone (MET) from human plasma. Preliminary assays were done before developing an experimental design based on a Uniform Network Doehlert which allowed the optimum extraction conditions to be identified, namely: a volume of extractant solvent (chloroform) and dispersant solvent (acetonitrile) of 220 µl and 3.2 ml, respectively; 0.2 g of NaCl as a salting-out additive; pH 10.6 and ultrasound stirring for 3.5 min. The resulting extracts were analyzed by high-performance liquid chromatography with photodiode array detection (HPLC-PDA), using an XBridge® RP18 column (250 × 4.6 mm i.d., 5 µm particle size). Calibration graphs were linear over the concentration range 0.1-10 µg ml⁻¹, and detection limits ranged from 13.9 to 28.5 ng ml⁻¹. Precision calculated at three different concentration levels in plasma was included in the range 0.1-6.8% RSD. Recoveries of the five drugs were all higher than 84% on average. Finally the proposed method was successfully applied to 22 plasma samples from heroin, cocaine and/or methadone users, and the most frequently detected drug was benzoylecgonine, followed by methadone, cocaine and morphine. Copyright © 2014 John Wiley & Sons, Ltd.

  19. Biodegradation of high concentrations of phenol by baker’s yeast in anaerobic sequencing batch reactor

    Directory of Open Access Journals (Sweden)

    Ali Asghar Najafpoor

    2015-06-01

    Full Text Available Background: Phenol, as a pure substance, is used in many fields because of its disinfectant, germicidal, local anesthetic, and peptizing properties. Aqueous solutions of phenol are produced as waste in industries and discharged into the environment. Therefore, elevated concentrations of phenol may be found in air or water because of industrial discharge or the use of phenolic products. Method: The strains of Saccharomyces cerevisiae used in this project were natural strains previously purchased from Razavy company. They were grown at 30°C on Petri plates containing yeast extract glucose (YGC and then purified by being spread onto new plates, and isolated colonies were obtained. These colonies provided the basis of selection. Prepared strains were applied in anaerobic sequencing batch reactors (ASBRs as first seed. The experiment conditions were optimized using response surface methodology (RSM. After the determined runs were performed using Design-Expert software, data were analyzed using mentioned software as well. Results: This study evaluated the capability of baker’s yeast to remove phenol in high concentrations. The tested strains showed excellent tolerance to phenol toxicity at concentrations up to 6100 mg/L. Study of the batch degradation process showed that the phenol removal rate could exceed 99.9% in 24 hours at a concentration of 1000 mg/L. The results showed catechol is the first intermediate product of phenol degradation. In survey results of the Design–Expert software, R2 and Adeq precision were 0.97 and 25.65, respectively. Conclusion: The results demonstrated that ASBR performs robustly under variable influent concentrations of inhibitory compounds. The high removal performance despite the high phenol concentration may be a result of reactor operating strategies. Based on the progressive increase of inlet phenol concentration, allowing for an enhanced biomass acclimation in a short time, results at the microbiological levels

  20. Generation of high-titer viral preparations by concentration using successive rounds of ultracentrifugation

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    Ichim Christine V

    2011-08-01

    Full Text Available Abstract Background Viral vectors provide a method of stably introducing exogenous DNA into cells that are not easily transfectable allowing for the ectopic expression or silencing of genes for therapeutic or experimental purposes. However, some cell types, in particular bone marrow cells, dendritic cells and neurons are difficult to transduce with viral vectors. Successful transduction of such cells requires preparation of highly concentrated viral stocks, which permit a high virus concentration and multiplicity of infection (MOI during transduction. Pseudotyping with the vesicular stomatitis virus G (VSV-G envelope protein is common practice for both lentiviral and retroviral vectors. The VSV-G glycoprotein adds physical stability to retroviral particles, allowing concentration of virus by high-speed ultracentrifugation. Here we describe a method report for concentration of virus from large volumes of culture supernatant by means of successive rounds of ultracentrifugation into the same ultracentrifuge tube. Method Stable retrovirus producer cell lines were generated and large volumes of virus-containing supernatant were produced. We then tested the transduction ability of virus following varying rounds of concentration by ultra-centrifugation. In a second series of experiments lentivirus-containing supernatant was produced by transient transfection of 297T/17 cells and again we tested the transduction ability of virus following multiple rounds of ultra-centrifugation. Results We report being able to centrifuge VSV-G coated retrovirus for as many as four rounds of ultracentrifugation while observing an additive increase in viral titer. Even after four rounds of ultracentrifugation we did not reach a plateau in viral titer relative to viral supernatant concentrated to indicate that we had reached the maximum tolerated centrifugation time, implying that it may be possible to centrifuge VSV-G coated retrovirus even further should it be necessary

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

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    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.

  2. Performance analysis of high-concentrated multi-junction solar cells in hot climate

    Science.gov (United States)

    Ghoneim, Adel A.; Kandil, Kandil M.; Alzanki, Talal H.; Alenezi, Mohammad R.

    2018-03-01

    Multi-junction concentrator solar cells are a promising technology as they can fulfill the increasing energy demand with renewable sources. Focusing sunlight upon the aperture of multi-junction photovoltaic (PV) cells can generate much greater power densities than conventional PV cells. So, concentrated PV multi-junction solar cells offer a promising way towards achieving minimum cost per kilowatt-hour. However, these cells have many aspects that must be fixed to be feasible for large-scale energy generation. In this work, a model is developed to analyze the impact of various atmospheric factors on concentrator PV performance. A single-diode equivalent circuit model is developed to examine multi-junction cells performance in hot weather conditions, considering the impacts of both temperature and concentration ratio. The impacts of spectral variations of irradiance on annual performance of various high-concentrated photovoltaic (HCPV) panels are examined, adapting spectra simulations using the SMARTS model. Also, the diode shunt resistance neglected in the existing models is considered in the present model. The present results are efficiently validated against measurements from published data to within 2% accuracy. Present predictions show that the single-diode model considering the shunt resistance gives accurate and reliable results. Also, aerosol optical depth (AOD) and air mass are most important atmospheric parameters having a significant impact on HCPV cell performance. In addition, the electrical efficiency (η) is noticed to increase with concentration to a certain concentration degree after which it decreases. Finally, based on the model predictions, let us conclude that the present model could be adapted properly to examine HCPV cells' performance over a broad range of operating conditions.

  3. Effects of the summer holiday season on UV filter and illicit drug concentrations in the Korean wastewater system and aquatic environment.

    Science.gov (United States)

    Kim, Ki Yong; Ekpeghere, Kalu Ibe; Jeong, Hee-Jin; Oh, Jeong-Eun

    2017-08-01

    Seasonal variations in the concentrations of eight ultraviolet (UV) filters and 22 illicit drugs including their metabolites in the Korean aquatic environment were investigated. Seawater samples from three beaches, water samples from two rivers, and influents and effluents from three wastewater treatment plants were analyzed. The UV filter concentrations in the seawater, river water, and effluent samples were 39.4-296, 35.4-117, and 6.84-51.1 ng L -1 , respectively. The total UV filter concentrations in the seawater samples were 1.9-4.4 times higher at the peak of the holiday season than outside the peak holiday season. An environmental risk assessment showed that ethylhexyl methoxy cinnamate (EHMC) could cause adverse effects on aquatic organisms in the seawater at the three beaches during the holiday period. Seven of the 22 target illicit drugs including their metabolites were detected in the wastewater influent samples, and the total illicit drug concentrations in the influent samples were 0.08-65.4 ng L -1 . The estimated daily consumption rates for cis-tramadol (Cis-TRM), methamphetamine (MTP), meperidine (MEP), and codeine (COD) were 25.7-118.4, 13.8-36.1, 1.36-12.6, and 1.75-8.64 mg d -1 (1000 people) -1 , respectively. In popular vacation area, the illicit drug consumption rates (Cis-TRM, MTP and MEP) were 1.6-2.6 times higher at the peak of the summer holiday season than at the beginning of the summer. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Serum vitamin E concentrations among highly functioning hip fracture patients are higher than in nonfracture controls.

    Science.gov (United States)

    D'Adamo, Christopher R; Shardell, Michelle D; Hicks, Gregory E; Orwig, Denise L; Hochberg, Marc C; Semba, Richard D; Yu-Yahiro, Janet A; Ferrucci, Luigi; Magaziner, Jay S; Miller, Ram R

    2011-03-01

    fracture patients demonstrated higher vitamin E concentrations. Thus, the relatively high degree of function among this cohort of hip fracture patients may explain their higher-than-expected vitamin E concentrations. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Fluidized bed combustion of single coal char particles at high CO{sub 2} concentration

    Energy Technology Data Exchange (ETDEWEB)

    Scala, F.; Chirone, R. [CNR, Naples (Italy)

    2010-12-15

    Combustion of single coal char particles was studied at 850{sup o}C in a lab-scale fluidized bed at high CO{sub 2} concentration, typical of oxyfiring conditions. The burning rate of the particles was followed as a function of time by continuously measuring the outlet CO and O{sub 2} concentrations. Some preliminary evaluations on the significance of homogeneous CO oxidation in the reactor and of carbon gasification by CO{sub 2} in the char were also carried out. Results showed that the carbon burning rate increases with oxygen concentration and char particle size. The particle temperature is approximately equal to that of the bed up to an oxygen concentration of 2%, but it is considerably higher for larger oxygen concentrations. Both CO{sub 2} gasification of char and homogeneous CO oxidation are not negligible. The gasification reaction rate is slow and it is likely to be controlled by intrinsic kinetics. During purely gasification conditions the extent of carbon loss due to particle attrition by abrasion (estimated from the carbon mass balance) appears to be much more important than under combustion conditions.

  6. Intestinal permeability study of minoxidil: assessment of minoxidil as a high permeability reference drug for biopharmaceutics classification.

    Science.gov (United States)

    Ozawa, Makoto; Tsume, Yasuhiro; Zur, Moran; Dahan, Arik; Amidon, Gordon L

    2015-01-05

    The purpose of this study was to evaluate minoxidil as a high permeability reference drug for Biopharmaceutics Classification System (BCS). The permeability of minoxidil was determined in in situ intestinal perfusion studies in rodents and permeability studies across Caco-2 cell monolayers. The permeability of minoxidil was compared with that of metoprolol, an FDA reference drug for BCS classification. In rat perfusion studies, the permeability of minoxidil was somewhat higher than that of metoprolol in the jejunum, while minoxidil showed lower permeability than metoprolol in the ileum. The permeability of minoxidil was independent of intestinal segment, while the permeability of metoprolol was region-dependent. Similarly, in mouse perfusion study, the jejunal permeability of minoxidil was 2.5-fold higher than that of metoprolol. Minoxidil and metoprolol showed similar permeability in Caco-2 study at apical pH of 6.5 and basolateral pH of 7.4. The permeability of minoxidil was independent of pH, while metoprolol showed pH-dependent transport in Caco-2 study. Minoxidil exhibited similar permeability in the absorptive direction (AP-BL) in comparison with secretory direction (BL-AP), while metoprolol had higher efflux ratio (ER > 2) at apical pH of 6.5 and basolateral pH of 7.4. No concentration-dependent transport was observed for either minoxidil or metoprolol transport in Caco-2 study. Verapamil did not alter the transport of either compounds across Caco-2 cell monolayers. The permeability of minoxidil was independent of both pH and intestinal segment in intestinal perfusion studies and Caco-2 studies. Caco-2 studies also showed no involvement of carrier mediated transport in the absorption process of minoxidil. These results suggest that minoxidil may be an acceptable reference drug for BCS high permeability classification. However, minoxidil exhibited higher jejunal permeability than metoprolol and thus to use minoxidil as a reference drug would raise the

  7. Technical note: False low turbidity readings from optical probes during high suspended-sediment concentrations

    Science.gov (United States)

    Voichick, Nicholas; Topping, David J.; Griffiths, Ronald E.

    2018-03-01

    Turbidity, a measure of water clarity, is monitored for a variety of purposes including (1) to help determine whether water is safe to drink, (2) to establish background conditions of lakes and rivers and detect pollution caused by construction projects and stormwater discharge, (3) to study sediment transport in rivers and erosion in catchments, (4) to manage siltation of water reservoirs, and (5) to establish connections with aquatic biological properties, such as primary production and predator-prey interactions. Turbidity is typically measured with an optical probe that detects light scattered from particles in the water. Probes have defined upper limits of the range of turbidity that they can measure. The general assumption is that when turbidity exceeds this upper limit, the values of turbidity will be constant, i.e., the probe is pegged; however, this assumption is not necessarily valid. In rivers with limited variation in the physical properties of the suspended sediment, at lower suspended-sediment concentrations, an increase in suspended-sediment concentration will cause a linear increase in turbidity. When the suspended-sediment concentration in these rivers is high, turbidity levels can exceed the upper measurement limit of an optical probe and record a constant pegged value. However, at extremely high suspended-sediment concentrations, optical turbidity probes do not necessarily stay pegged at a constant value. Data from the Colorado River in Grand Canyon, Arizona, USA, and a laboratory experiment both demonstrate that when turbidity exceeds instrument-pegged conditions, increasing suspended-sediment concentration (and thus increasing turbidity) may cause optical probes to record decreasing false turbidity values that appear to be within the valid measurement range of the probe. Therefore, under high-turbidity conditions, other surrogate measurements of turbidity (e.g., acoustic-attenuation measurements or suspended-sediment samples) are necessary to

  8. Novel bioevaporation process for the zero-discharge treatment of highly concentrated organic wastewater.

    Science.gov (United States)

    Yang, Benqin; Zhang, Lei; Lee, Yongwoo; Jahng, Deokjin

    2013-10-01

    A novel process termed as bioevaporation was established to completely evaporate wastewater by metabolic heat released from the aerobic microbial degradation of the organic matters contained in the highly concentrated organic wastewater itself. By adding the glucose solution and ground food waste (FW) into the biodried sludge bed, the activity of the microorganisms in the biodried sludge was stimulated and the water in the glucose solution and FW was evaporated. As the biodegradable volatile solids (BVS) concentration in wastewater increased, more heat was produced and the water removal ratio increased. When the volatile solids (VS) concentrations of both glucose and ground FW were 120 g L(-1), 101.7% and 104.3% of the added water was removed, respectively, by completely consuming the glucose and FW BVS. Therefore, the complete removal of water and biodegradable organic contents was achieved simultaneously in the bioevaporation process, which accomplished zero-discharge treatment of highly concentrated organic wastewater. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. High Pb concentration stress on Typha latifolia growth and Pb removal in microcosm wetlands.

    Science.gov (United States)

    Han, Jianqiu; Chen, Fengzhen; Zhou, Yumei; Wang, Chaohua

    2015-01-01

    When constructed wetlands are used to treat high-Pb wastewater, Pb may become a stress to wetland plants, which subsequently reduces treatment performance and the other ecosystem services. To facilitate the design and operation of constructed wetlands for treatment of Pb-rich wastewater, we investigated the irreversible inhibitory level of Pb for Typha latifolia through experiments in microcosm wetlands. Seven horizontal subsurface flow constructed wetlands were built with rectangular plastic tanks and packed with marble chips and sand. All wetlands were transplanted with nine stems of Typha latifolia each. The wetlands were batch operated in a greenhouse with artificial wastewater (10 L each) for 12 days. Influent to the seven wetlands had different concentrations of Pb: 0 mg/L, 10 mg/L, 25 mg/L, 50 mg/L, 100 mg/L, 200 mg/L, and 500 mg/L, respectively. The results suggested that leaf chlorophyll relative content, relative growth rate, photosynthetic characteristics, activities of superoxide dismutase, peroxidase, and content of malondialdehyde were not affected when initial Pb concentration was at 100 mg/L and below. But when initial Pb concentration was above 100 mg/L, all of them were seriously affected. We conclude that high Pb concentrations wastewater could inhibit the growth of Typha latifolia and decrease the removal rate of wetlands.

  10. Investigation on the improved radiation hardness of silicon detectors with high oxygen concentration

    CERN Document Server

    Moll, Michael; Lindström, G

    2000-01-01

    We present an investigation on the influence of the oxygen concentration on radiation-induced changes in the effective doping concentration of silicon detectors. Diodes fabricated from silicon with interstitial oxygen content ranging from below 2*10/sup 14/ to 9*10/sup 17/ cm/sup -3/ have been irradiated with fast neutrons up to a fluence of 2*10/sup 15/ cm/sup -2/. Our main interest focused on the so-called stable damage component in the change of the effective doping concentration being of prime importance for the application of silicon detectors in high-energy physics experiments. We demonstrate, that with a high oxygen enrichment the donor removal is appreciably reduced, reaching a value of only 10601130f the initial doping concentration for [O/sub i/]=9*10/sup 17/ cm/sup -3/, while for normal detector grade material with [O/sub i/] below 5*10/sup 16/ cm /sup -3/ that value is 60-90Furthermore, we show that the fluence proportional introduction of stable acceptors is independent of the oxygen concentratio...

  11. Concentrate Supplement Modifies the Feeding Behavior of Simmental Cows Grazing in Two High Mountain Pastures.

    Science.gov (United States)

    Romanzin, Alberto; Corazzin, Mirco; Piasentier, Edi; Bovolenta, Stefano

    2018-05-16

    During grazing on Alpine pastures, the use of concentrates in dairy cows' diet leads to a reduction of the environmental sustainability of farms, and influences the selective pressure on some plant species. In order to minimize the use of concentrates, it is imperative to obtain data on the grazing behavior of cows. The aim of this study was to assess the effect of concentrate levels on the behavior of dairy cows during grazing. One hundred and ten lactating Italian Simmental cows, that sequentially grazed two pastures characterized by Poion alpinae (Poion) and Seslerion caeruleae (Seslerion) alliance, were considered. For each pasture, eight cows were selected and assigned to two groups: High and Low, supplemented with 4 kg/head/d, and 1 kg/head/d of concentrate respectively. Cows were equipped with a noseband pressure sensor and a pedometer (RumiWatch system, ITIN-HOCH GmbH) to assess grazing, ruminating, and walking behavior. In addition, the plant selection of the animals was assessed. On Poion, increased supplement intake caused a more intense selection of legumes, without affecting feeding and walking times. On Seslerion, grazing time was higher in Low than High. Grazing management in alpine region must take into account the great variability of pastures that largely differ from a floristic and nutritional point of view.

  12. Concentrate Supplement Modifies the Feeding Behavior of Simmental Cows Grazing in Two High Mountain Pastures

    Directory of Open Access Journals (Sweden)

    Alberto Romanzin

    2018-05-01

    Full Text Available During grazing on Alpine pastures, the use of concentrates in dairy cows’ diet leads to a reduction of the environmental sustainability of farms, and influences the selective pressure on some plant species. In order to minimize the use of concentrates, it is imperative to obtain data on the grazing behavior of cows. The aim of this study was to assess the effect of concentrate levels on the behavior of dairy cows during grazing. One hundred and ten lactating Italian Simmental cows, that sequentially grazed two pastures characterized by Poion alpinae (Poion and Seslerion caeruleae (Seslerion alliance, were considered. For each pasture, eight cows were selected and assigned to two groups: High and Low, supplemented with 4 kg/head/d, and 1 kg/head/d of concentrate respectively. Cows were equipped with a noseband pressure sensor and a pedometer (RumiWatch system, ITIN-HOCH GmbH to assess grazing, ruminating, and walking behavior. In addition, the plant selection of the animals was assessed. On Poion, increased supplement intake caused a more intense selection of legumes, without affecting feeding and walking times. On Seslerion, grazing time was higher in Low than High. Grazing management in alpine region must take into account the great variability of pastures that largely differ from a floristic and nutritional point of view.

  13. High Concentrations of Measles Neutralizing Antibodies and High-Avidity Measles IgG Accurately Identify Measles Reinfection Cases

    Science.gov (United States)

    Rota, Jennifer S.; Hickman, Carole J.; Mercader, Sara; Redd, Susan; McNall, Rebecca J.; Williams, Nobia; McGrew, Marcia; Walls, M. Laura; Rota, Paul A.; Bellini, William J.

    2016-01-01

    In the United States, approximately 9% of the measles cases reported from 2012 to 2014 occurred in vaccinated individuals. Laboratory confirmation of measles in vaccinated individuals is challenging since IgM assays can give inconclusive results. Although a positive reverse transcription (RT)-PCR assay result from an appropriately timed specimen can provide confirmation, negative results may not rule out a highly suspicious case. Detection of high-avidity measles IgG in serum samples provides laboratory evidence of a past immunologic response to measles from natural infection or immunization. High concentrations of measles neutralizing antibody have been observed by plaque reduction neutralization (PRN) assays among confirmed measles cases with high-avidity IgG, referred to here as reinfection cases (RICs). In this study, we evaluated the utility of measuring levels of measles neutralizing antibody to distinguish RICs from noncases by receiver operating characteristic curve analysis. Single and paired serum samples with high-avidity measles IgG from suspected measles cases submitted to the CDC for routine surveillance were used for the analysis. The RICs were confirmed by a 4-fold rise in PRN titer or by RT-quantitative PCR (RT-qPCR) assay, while the noncases were negative by both assays. Discrimination accuracy was high with serum samples collected ≥3 days after rash onset (area under the curve, 0.953; 95% confidence interval [CI], 0.854 to 0.993). Measles neutralizing antibody concentrations of ≥40,000 mIU/ml identified RICs with 90% sensitivity (95% CI, 74 to 98%) and 100% specificity (95% CI, 82 to 100%). Therefore, when serological or RT-qPCR results are unavailable or inconclusive, suspected measles cases with high-avidity measles IgG can be confirmed as RICs by measles neutralizing antibody concentrations of ≥40,000 mIU/ml. PMID:27335386

  14. 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.

  15. High Concentration of Melatonin Regulates Leaf Development by Suppressing Cell Proliferation and Endoreduplication in Arabidopsis.

    Science.gov (United States)

    Wang, Qiannan; An, Bang; Shi, Haitao; Luo, Hongli; He, Chaozu

    2017-05-05

    N -acetyl-5-methoxytryptamine (Melatonin), as a crucial messenger in plants, functions in adjusting biological rhythms, stress tolerance, plant growth and development. Several studies have shown the retardation effect of exogenous melatonin treatment on plant growth and development. However, the in vivo role of melatonin in regulating plant leaf growth and the underlying mechanism are still unclear. In this study, we found that high concentration of melatonin suppressed leaf growth in Arabidopsis by reducing both cell size and cell number. Further kinetic analysis of the fifth leaves showed that melatonin remarkably inhibited cell division rate. Additionally, flow cytometic analysis indicated that melatonin negatively regulated endoreduplication during leaf development. Consistently, the expression analysis revealed that melatonin regulated the transcriptional levels of key genes of cell cycle and ribosome. Taken together, this study suggests that high concentration of melatonin negatively regulated the leaf growth and development in Arabidopsis , through modulation of endoreduplication and the transcripts of cell cycle and ribosomal key genes.

  16. High pressure-temperature electrical conductivity of magnesiowustite as a function of iron oxide concentration

    Science.gov (United States)

    Li, Xiaoyuan; Jeanloz, Raymond

    1990-01-01

    The electrical conductivity of (Mg, Fe)O magnesiowustite containing 9 and 27.5 mol pct FeO has been measured at simultaneously high pressures (30-32 GPa) and temperatures using a diamond anvil cell heated with a continuous wave Nd:YAG laser and an external resistance heater. The conductivity depends strongly on the FeO concentration at both ambient and high pressures. At the pressures and temperatures of about 30 GPa and 2000 K, conditions expected in the lower mantle, the magnesiowustite containing 27.5 percent FeO is 3 orders of magnitude more conductive than that containing 9 percent FeO. The activation energy of magnesiowustite decreases with increasing iron concentration from 0.38 (+ or - 0.09) eV at 9 percent FeO to 0.29 (+ or - 0.05) eV at 27.5 percent FeO.

  17. High concentrations of cadmium, cerium and lanthanum in indoor air due to environmental tobacco smoke

    International Nuclear Information System (INIS)

    Böhlandt, Antje; Schierl, Rudolf; Diemer, Juergen; Koch, Christoph; Bolte, Gabriele; Kiranoglu, Mandy; Fromme, Hermann; Nowak, Dennis

    2012-01-01

    Background: Environmental tobacco smoke (ETS) is one of the most important sources for indoor air pollution and a substantial threat to human health, but data on the concentrations of the trace metals cerium (Ce) and lanthanum (La) in context with ETS exposure are scarce. Therefore the aim of our study was to quantify Ce and La concentrations in indoor air with high ETS load. Methods: In two subsequent investigations Ce, La and cadmium (Cd) in 3 smokers' (11 samples) and 7 non-smokers' (28 samples) households as well as in 28 hospitality venues in Southern Germany were analysed. Active sampling of indoor air was conducted continuously for seven days in every season in the smokers' and non-smokers' residences, and for 4 h during the main visiting hours in the hospitality venues (restaurants, pubs, and discotheques). Results: In terms of residences median levels of Cd were 0.1 ng/m 3 for non-smokers' and 0.8 ng/m 3 for smokers' households. Median concentrations of Ce were 0.4 ng/m 3 and 9.6 ng/m 3 , and median concentrations of La were 0.2 ng/m 3 and 5.9 ng/m 3 for non-smokers' and for smokers' households, respectively. In the different types of hospitality venues median levels ranged from 2.6 to 9.7 ng/m 3 for Cd, from 18.5 to 50.0 ng/m 3 for Ce and from 10.6 to 23.0 ng/m 3 for La with highest median levels in discotheques. Conclusions: The high concentrations of Ce and La found in ETS enriched indoor air of smokers' households and hospitality venues are an important finding as Ce and La are associated with adverse health effects and data on this issue are scarce. Further research on their toxicological, human and public health consequences is urgently required. - Highlights: ► We quantified cer, lanthanum and cadmium concentrations in indoor air. ► Cer and lanthanum concentrations were high in tobacco smoke enriched locations. ► Both elements can be considered as good markers for indoor air quality.

  18. Hypercalcemia and high parathyroid hormone-related protein concentration associated with malignant melanoma in a dog.

    Science.gov (United States)

    Pressler, Barrak M; Rotstein, David S; Law, Jerry M; Rosol, Thomas J; LeRoy, Bruce; Keene, Bruce W; Jackson, Mark W

    2002-07-15

    A 12-year-old Cocker Spaniel with an oral malignant melanoma was evaluated for progressive lethargy and anorexia. No metastases were identified during antemortem evaluation, but severe hypercalcemia was evident. Antemortem diagnostic testing failed to identify a cause for the hypercalcemia. No neoplasms other than the melanoma were identified on postmortem examination. Serum parathyroid hormone-related protein concentration was markedly high, and the melanoma had moderate to marked immunostaining for this protein. Paraneoplastic syndromes are rare in dogs with malignant melanoma.

  19. Effect of high concentration of molybdenum on the structure and properties of niobium

    International Nuclear Information System (INIS)

    Trekina, M.I.; Vasil'eva, E.V.

    1989-01-01

    The effect of alloying of 20,25 and 30 % Mo on the structure and mechanical properties of niobium is studied. It is shown that niobium alloying with molybdenum in the studied concentration leads to grain grinding, which increases with the molybdenum content growth in the alloy. The effective energy values of recrystallization activation of the studied niobium and molybdenum alloys are determined. The high hardness level at some plasticity and deformability of niobium alloy with 20 % Mo is established

  20. Natural radionuclides in food in an area with high concentrations of radionuclides

    International Nuclear Information System (INIS)

    Pereira, W.S.; Moraes, S.R.; Cavalcante, J.J.V.; Kelecom, A.; Silva, A.X. da; Lopez, J.M.; Filgueiras, R.; Carmo, A.S.

    2017-01-01

    Areas of high natural radiation expose the local population to doses greater than the world average. One of the routes of exposure is food intake. The activity concentration (AC) of 5 natural radionuclides in 7 types of foods was analyzed. The highest CA measured was 2.40 Bq.kg -1 for the U nat in the potato. The multivariate statistic identified two groups: (U nat e 232 Th) and [( 210 Pb and 228 Ra) and 226 Ra

  1. 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.

  2. High concentrations of heavy metals in PM from ceramic factories of Southern Spain

    Science.gov (United States)

    Sánchez de la Campa, Ana M.; de la Rosa, Jesús D.; González-Castanedo, Yolanda; Fernández-Camacho, Rocío; Alastuey, Andrés; Querol, Xavier; Pio, Casimiro

    2010-06-01

    In this study, physicochemical characterization of Atmospheric Particulate Matter (PM) was performed in an urban-industrial site background (Bailén, Southern Spain), highly influenced by the impact of emission plumes from ceramic factories. This area is considered one of the towns with the highest PM 10 levels and average SO 2 concentration in Spain. A three stages methodology was used: 1) real-time measurements of levels of PM 10 and gaseous pollutants, and sampling of PM; 2) chemical characterization using ICP-MS, ICP-OES, CI and TOT, and source apportionment analysis (receptor modelling) of PM; and 3) chemical characterization of emission plumes derived from representative factories. High ambient air concentrations were found for most major components and trace elements compared with other industrialized towns in Spain. V and Ni are considered fingerprints of PM derived from the emissions of brick factories in this area, and were shown to be of particular interest. This highlights the high V and Ni concentrations in PM 10 (122 ngV/m 3 and 23.4 ngNi/m 3), with Ni exceeding the 2013 annual target value for the European Directive 2004/107/EC (20 ng/m 3). The methodology of this work can be used by Government departments responsible for Environment and Epidemiology in planning control strategies for improving air quality.

  3. 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...

  4. Direct Analysis of Proteins from Solutions with High Salt Concentration Using Laser Electrospray Mass Spectrometry

    Science.gov (United States)

    Karki, Santosh; Shi, Fengjian; Archer, Jieutonne J.; Sistani, Habiballah; Levis, Robert J.

    2018-05-01

    The detection of lysozyme, or a mixture of lysozyme, cytochrome c, and myoglobin, from solutions with varying salt concentrations (0.1 to 250 mM NaCl) is compared using laser electrospray mass spectrometry (LEMS) and electrospray ionization-mass spectrometry (ESI-MS). Protonated protein peaks were observed up to a concentration of 250 mM NaCl in the case of LEMS. In the case of ESI-MS, a protein solution with salt concentration > 0.5 mM resulted in predominantly salt-adducted features, with suppression of the protonated protein ions. The constituents in the mixture of proteins were assignable up to 250 mM NaCl for LEMS and were not assignable above a NaCl concentration of 0.5 mM for ESI. The average sodium adducts () bound to the 7+ charge state of lysozyme for LEMS measurements from salt concentrations of 2.5, 25, 50, and 100 mM NaCl are 1.71, 5.23, 5.26, and 5.11, respectively. The conventional electrospray measurements for lysozyme solution containing salt concentrations of 0.1, 1, 2, and 5 mM NaCl resulted in of 2.65, 6.44, 7.57, and 8.48, respectively. LEMS displays an approximately two orders of magnitude higher salt tolerance in comparison with conventional ESI-MS. The non-equilibrium partitioning of proteins on the surface of the charged droplets is proposed as the mechanism for the high salt tolerance phenomena observed in the LEMS measurements. [Figure not available: see fulltext.

  5. Modulating fluorescence quantum yield of highly concentrated fluorescein using differently shaped green synthesized gold nanoparticles

    International Nuclear Information System (INIS)

    John, Jisha; Thomas, Lincy; Kurian, Achamma; George, Sajan D.

    2016-01-01

    The interaction of dye molecules with differently shaped nanoparticles is of great interest owing to the potential applications in areas of bioimaging, sensing and photodynamic therapy (biology) as well as solar cells (photonics) applications. For such applications, noble metallic nanoparticles are commonly employed to either enhance or quench the luminescence of a nearby fluorophore. However, in most of the studies, the dye concentration is limited to avoid self-quenching. This paper reports the influence of differently shaped gold nanoparticles (spherical, bean and star), prepared via green synthesis, on the emission behavior as well as on the fluorescence quantum yield of fluorescein dye at concentrations for which self-quenching occurs. The emission behavior is probed via laser based steady state fluorescence whereas quantum yield is measured using a dual beam laser based thermal lens technique. The experimentally observed fluorescence quenching with a concomitant increase in thermal lens signal in the vicinity of nanoparticles are explained in terms of nonradiative energy transfer between the donor and the acceptor. Further, the influence of pH of the prepared gold nanofluid on the absorption, emission as well as quantum yield are also accounted. These studies elucidate that even at high concentrations of dye, the gold nanoparticle and its shape clearly influences the optical properties of nearby dye molecules and thus can be exploited for future applications. - Highlights: • Green synthesis of differently shaped gold nanoparticles. • Tailoring emission properties of fluorescein with respect to nanoparticle concentration and shape. • Tailoring the quantum yield of highly concentrated fluorescein with nanoparticles.

  6. Investigation on the improved radiation hardness of silicon detectors with high oxygen concentration

    International Nuclear Information System (INIS)

    Moll, M.; Fretwurst, E.; Lindstroem, G.

    2000-01-01

    We present an investigation on the influence of the oxygen concentration on radiation-induced changes in the effective doping concentration of silicon detectors. Diodes fabricated from silicon with interstitial oxygen content ranging from below 2x10 14 to 9x10 17 cm -3 have been irradiated with fast neutrons up to a fluence of 2x10 15 cm -2 . Our main interest focused on the so-called stable damage component in the change of the effective doping concentration being of prime importance for the application of silicon detectors in high-energy physics experiments. We demonstrate, that with a high oxygen enrichment the donor removal is appreciably reduced, reaching a value of only 10% of the initial doping concentration for [O i ]=9x10 17 cm -3 , while for normal detector grade material with [O i ] below 5x10 16 cm -3 that value is 60-90%. Furthermore, we show that the fluence proportional introduction of stable acceptors is independent of the oxygen concentration with an averaged introduction rate of (1.49±0.03)x10 -2 cm -1 . Only one material was found exhibiting a significantly smaller value of about 0.6x10 -2 cm -1 and thus indicating the possibility to suppress the radiation-induced acceptor creation by material modification. Finally, we show that the experimental findings disagree in several important aspects with predictions made by microscopic defect kinetics models, leaving the physical background of some of the measured data as an open question

  7. Relationship of peak serum methotrexate concentration to prognosis and drug tolerance in non-metastatic extremity osteosarcomas.

    Science.gov (United States)

    Wang, Bo; Yao, Hao; Xie, Xianbiao; Yin, Junqiang; Zou, Changye; Huang, Gang; Shen, Jingnan

    2018-05-28

    This study aimed to explore whether peak serum methotrexate concentration (C max ) correlated with adverse events, overall survival (OS) and event-free survival (EFS) in patients with primary extremity osteosarcoma. Patients with extremity osteosarcoma who were treated at our center between 2005 and 2015 were retrospectively studied. All the patients were Enneking stage II and had received standard perioperative chemotherapy composed of high-dose methotrexate, doxorubicin, cisplatin and ifosfamide. C max and treatment-associated toxicities of each cycle were recorded. OS and EFS were estimated and compared by Kaplan-Meier survival analysis, and Cox regression models were performed for univariate comparisons. In total, 567 patients were followed for an average of 53 months (24-104 months). The estimated 3- and 5-year EFS were 71.7 and 63.1%, and the 3- and 5-year OS were 78.2 and 72.9%, respectively. C max ranged from 527 to 2495 µmol/L with a mean value of 931 ± 106 µmol/L. No significant differences in EFS and OS (p = 0.18 and p = 0.28) were observed among patients with a mean C max  > 1500, > 1000, > 700 and  1500 µmol/L had significantly increased rates of grade 3-5 toxicity. In the univariate analysis, C max was not a prognostic factor for EFS (p = 0.08) or OS (p = 0.16). C max did not correlate significantly with the oncologic prognosis of non-metastatic extremity osteosarcoma patients treated by multi-agent chemotherapy; however, C max correlated closely with toxicities and complications. The persistent inclusion of methotrexate in classical multidisciplinary chemotherapy was questioned and should be examined in future trials.

  8. On the peculiarities of LDA method in two-phase flows with high concentrations of particles

    Science.gov (United States)

    Poplavski, S. V.; Boiko, V. M.; Nesterov, A. U.

    2016-10-01

    Popular applications of laser Doppler anemometry (LDA) in gas dynamics are reviewed. It is shown that the most popular method cannot be used in supersonic flows and two-phase flows with high concentrations of particles. A new approach to implementation of the known LDA method based on direct spectral analysis, which offers better prospects for such problems, is presented. It is demonstrated that the method is suitable for gas-liquid jets. Owing to the progress in laser engineering, digital recording of spectra, and computer processing of data, the method is implemented at a higher technical level and provides new prospects of diagnostics of high-velocity dense two-phase flows.

  9. [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.

  10. 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.

  11. 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.

  12. Linezolid Trough Concentrations Correlate with Mitochondrial Toxicity-Related Adverse Events in the Treatment of Chronic Extensively Drug-Resistant Tuberculosis.

    Science.gov (United States)

    Song, Taeksun; Lee, Myungsun; Jeon, Han-Seung; Park, Yumi; Dodd, Lori E; Dartois, Véronique; Follman, Dean; Wang, Jing; Cai, Ying; Goldfeder, Lisa C; Olivier, Kenneth N; Xie, Yingda; Via, Laura E; Cho, Sang Nae; Barry, Clifton E; Chen, Ray Y

    2015-11-01

    Long-term linezolid use is limited by mitochondrial toxicity-associated adverse events (AEs). Within a prospective, randomized controlled trial of linezolid to treat chronic extensively drug-resistant tuberculosis, we serially monitored the translational competence of mitochondria isolated from peripheral blood of participants by determining the cytochrome c oxidase/citrate synthase activity ratio. We compared this ratio with AEs associated with mitochondrial dysfunction. Linezolid trough concentrations were determined for 38 participants at both 600 mg and 300 mg doses. Those on 600 mg had a significantly higher risk of AE than those on 300 mg (HR 3·10, 95% CI 1·23-7 · 86). Mean mitochondrial function levels were significantly higher in patients before starting linezolid compared to their concentrations on 300 mg (P = 0·004) or 600 mg (P linezolid trough concentrations were associated with lower mitochondrial function levels (Spearman's ρ = - 0.48; P = 0.005). Mitochondrial toxicity risk increased with increasing linezolid trough concentrations, with all patients with mean linezolid trough > 2 μg/ml developing an AE related to mitochondrial toxicity, whether on 300 mg or 600 mg. Therapeutic drug monitoring may be useful to prevent the development of mitochondrial toxicity associated with long-term linezolid use.

  13. 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.

  14. Estimating NOx emissions and surface concentrations at high spatial resolution using OMI

    Science.gov (United States)

    Goldberg, D. L.; Lamsal, L. N.; Loughner, C.; Swartz, W. H.; Saide, P. E.; Carmichael, G. R.; Henze, D. K.; Lu, Z.; Streets, D. G.

    2017-12-01

    In many instances, NOx emissions are not measured at the source. In these cases, remote sensing techniques are extremely useful in quantifying NOx emissions. Using an exponential modified Gaussian (EMG) fitting of oversampled Ozone Monitoring Instrument (OMI) NO2 data, we estimate NOx emissions and lifetimes in regions where these emissions are uncertain. This work also presents a new high-resolution OMI NO2 dataset derived from the NASA retrieval that can be used to estimate surface level concentrations in the eastern United States and South Korea. To better estimate vertical profile shape factors, we use high-resolution model simulations (Community Multi-scale Air Quality (CMAQ) and WRF-Chem) constrained by in situ aircraft observations to re-calculate tropospheric air mass factors and tropospheric NO2 vertical columns during summertime. The correlation between our satellite product and ground NO2 monitors in urban areas has improved dramatically: r2 = 0.60 in new product, r2 = 0.39 in operational product, signifying that this new product is a better indicator of surface concentrations than the operational product. Our work emphasizes the need to use both high-resolution and high-fidelity models in order to re-calculate vertical column data in areas with large spatial heterogeneities in NOx emissions. The methodologies developed in this work can be applied to other world regions and other satellite data sets to produce high-quality region-specific emissions estimates.

  15. Comparison of Low Concentration and High Concentration Arsenic Removal Techniques and Evaluation of Concentration of Arsenic in Ground Water: A Case Study of Lahore, Pakistan

    International Nuclear Information System (INIS)

    Yasar, Abdullah; Tabinda, Amtul Bari; Shahzadi, Uzma; Saleem, Pakeeza

    2014-01-01

    The main focus of this study was the evaluation of arsenic concentration in the ground water of Lahore at different depth and application of different mitigation techniques for arsenic removal. Twenty four hours of solar oxidation gives 90% of arsenic removal as compared to 8 hr. or 16 hr. Among oxides, calcium oxide gives 96% of As removal as compared to 93% by lanthanum oxide. Arsenic removal efficiency was up to 97% by ferric chloride, whereas 95% by alum. Activated alumina showed 99% removal as compared to 97% and 95% removal with bauxite and charcoal, respectively. Elemental analysis of adsorbents showed that the presence of phosphate and silica can cause a reduction of arsenic removal efficiency by activated alumina, bauxite and charcoal. This study has laid a foundation for further research on arsenic in the city of Lahore and has also provided suitable techniques for arsenic removal

  16. Comparison of Low Concentration and High Concentration Arsenic Removal Techniques and Evaluation of Concentration of Arsenic in Ground Water: A Case Study of Lahore, Pakistan

    Energy Technology Data Exchange (ETDEWEB)

    Yasar, Abdullah; Tabinda, Amtul Bari; Shahzadi, Uzma; Saleem, Pakeeza [GC University, Lahore (Pakistan)

    2014-10-15

    The main focus of this study was the evaluation of arsenic concentration in the ground water of Lahore at different depth and application of different mitigation techniques for arsenic removal. Twenty four hours of solar oxidation gives 90% of arsenic removal as compared to 8 hr. or 16 hr. Among oxides, calcium oxide gives 96% of As removal as compared to 93% by lanthanum oxide. Arsenic removal efficiency was up to 97% by ferric chloride, whereas 95% by alum. Activated alumina showed 99% removal as compared to 97% and 95% removal with bauxite and charcoal, respectively. Elemental analysis of adsorbents showed that the presence of phosphate and silica can cause a reduction of arsenic removal efficiency by activated alumina, bauxite and charcoal. This study has laid a foundation for further research on arsenic in the city of Lahore and has also provided suitable techniques for arsenic removal.

  17. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

    Science.gov (United States)

    Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

    2015-01-01

    Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

  18. A highly concentrated diet increases biogas production and the agronomic value of young bull's manure.

    Science.gov (United States)

    Mendonça Costa, Mônica Sarolli Silva de; Lucas, Jorge de; Mendonça Costa, Luiz Antonio de; Orrico, Ana Carolina Amorim

    2016-02-01

    The increasing demand for animal protein has driven significant changes in cattle breeding systems, mainly in feedlots, with the use of young bulls fed on diets richer in concentrate (C) than in forage (F). These changes are likely to affect animal manure, demanding re-evaluation of the biogas production per kg of TS and VS added, as well as of its agronomic value as a biofertilizer, after anaerobic digestion. Here, we determined the biogas production and agronomic value (i.e., the macronutrient concentration in the final biofertilizer) of the manure of young bulls fed on diets with more (80% C+20% F; 'HighC' diet) or less (65% C+35% F; 'LowC' diet) concentrate, evaluating the effects of temperature (25, 35, and 40°C) and the use of an inoculum, during anaerobic digestion. A total of 24 benchtop reactors were used, operating in a semi-continuous system, with a 40-day hydraulic retention time (HRT). The manure from animals given the HighC diet had the greatest potential for biogas production, when digested with the use of an inoculum and at 35 or 40°C (0.6326 and 0.6207m(3)biogas/kg volatile solids, or VS, respectively). We observed the highest levels of the macronutrients N, P, and K in the biofertilizer from the manure of animals given HighC. Our results show that the manure of young bulls achieves its highest potential for biogas production and agronomic value when animals are fed diets richer in concentrate, and that biogas production increases if digestion is performed at higher temperatures, and with the use of an inoculum. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. High fetal plasma adenosine concentration: a role for the fetus in preeclampsia?

    LENUS (Irish Health Repository)

    Espinoza, Jimmy

    2012-02-01

    OBJECTIVE: Clinical observations suggest a role for the fetus in the maternal manifestations of preeclampsia, but the possible signaling mechanisms remain unclear. This study compares the fetal plasma concentrations of adenosine from normal pregnancies with those from preeclampsia. STUDY DESIGN: This secondary data analysis included normal pregnancies (n = 27) and patients with preeclampsia (n = 39). Patients with preeclampsia were subclassified into patients with (n = 25) and without (n = 14) abnormal uterine artery Doppler velocimetry (UADV). RESULTS: Fetal plasma concentrations of adenosine were significantly higher in patients with preeclampsia (1.35 +\\/- 0.09 mumol\\/L) than in normal pregnancies (0.52 +\\/- 0.06 mumol\\/L; P < .0001). Fetal plasma concentrations of adenosine in patients with preeclampsia with abnormal UADV (1.78 +\\/- 0.15 mumol\\/L), but not with normal UADV (0.58 +\\/- 0.14 mumol\\/L), were significantly higher than in normal pregnancies (P < .0001). CONCLUSION: Patients with preeclampsia with sonographic evidence of chronic uteroplacental ischemia have high fetal plasma concentrations of adenosine.

  20. Origin of methane and sources of high concentrations in Los Angeles groundwater

    Science.gov (United States)

    Kulongoski, Justin; McMahon, Peter B.; Land, Michael; Wright, Michael; Johnson, Theodore; Landon, Matthew K.

    2018-01-01

    In 2014, samples from 37 monitoring wells at 17 locations, within or near oil fields, and one site >5 km from oil fields, in the Los Angeles Basin, California, were analyzed for dissolved hydrocarbon gas isotopes and abundances. The wells sample a variety of depths of an aquifer system composed of unconsolidated and semiconsolidated sediments under various conditions of confinement. Concentrations of methane in groundwater samples ranged from 0.002 to 150 mg/L—some of the highest concentrations reported in a densely populated urban area. The δ13C and δ2H of the methane ranged from −80.8 to −45.5 per mil (‰) and −249.8 to −134.9‰, respectively, and, along with oxidation‐reduction processes, helped to identify the origin of methane as microbial methanogenesis and CO2 reduction as its main formation pathway. The distribution of methane concentrations and isotopes is consistent with the high concentrations of methane in Los Angeles Basin groundwater originating from relatively shallow microbial production in anoxic or suboxic conditions. Source of the methane is the aquifer sediments rather than the upward migration or leakage of thermogenic methane associated with oil fields in the basin.

  1. The ability of fungus Mucor racemosus Fresenius to degrade high concentration of detergent

    Directory of Open Access Journals (Sweden)

    Jakovljević Violeta D.

    2014-01-01

    Full Text Available The ability of fungus Mucor racemosus Fresenius to decompose high concentration of commercial detergent (MERIX, Henkel, Serbia was investigated in this study. Fungus was cultivated in liquid growth medium by Czapek with addition of detergent at concentration 0.5% during 16 days. The biochemical changes of pH, redox potential, amount of free and total organic acids, and activity of alkaline phosphatase were evaluated by analysis of fermentation broth. Simultaneously, biodegradation percentage of anionic surfactant of tested detergent was confirmed by MBAS assay. At the same time, the influence of detergent on fungal growth and total dry weight biomass was determined. Detergent at concentration 0.5% influenced on decreasing of pH value and increasing of redox potential as well as increasing of free and total organic acids. Enzyme activity of alkaline phosphatase was reduced by detergent at concentration 0.5%. The fungus was decomposed about 62% of anionic surfactant during 16 day. Due to fungus was produced higher dry weight biomass (53% in relation to control. [Projekat Ministarstva nauke Republike Srbije, br. III 43004

  2. [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.

  3. Is a high serum copper concentration a risk factor for implantation failure?

    Science.gov (United States)

    Matsubayashi, Hidehiko; Kitaya, Kotaro; Yamaguchi, Kohei; Nishiyama, Rie; Takaya, Yukiko; Ishikawa, Tomomoto

    2017-08-10

    Copper-containing contraceptive devices may deposit copper ions in the endometrium, resulting in implantation failure. The deposition of copper ions in many organs has been reported in patients with untreated Wilson's disease. Since these patients sometimes exhibit subfertility and/or early pregnancy loss, copper ions were also considered to accumulate in the uterine endometrium. Wilson's disease patients treated with zinc successfully delivered babies because zinc interfered with the absorption of copper from the gastrointestinal tract. These findings led to the hypothesis that infertile patients with high serum copper concentrations may have implantation failure due to the excess accumulation of copper ions. The relationship between implantation (pregnancy) rates and serum copper concentrations has not yet been examined. The Japanese government recently stated that actual copper intake was higher among Japanese than needed. Therefore, the aim of the present study was to investigate whether serum copper concentrations are related to the implantation (pregnancy) rates of human embryos in vivo. We included 269 patients (age copper, and zinc concentrations were measured 16 days after the first date of progesterone replacement. We compared 96 women who were pregnant without miscarriage at 10 weeks of gestation (group P) and 173 women who were not pregnant (group NP). No significant differences were observed in age or BMI between the groups. Copper concentrations were significantly higher in group NP (average 193.2 μg/dL) than in group P (average 178.1 μg/dL). According to the area under the curve (AUC) on the receiver operating characteristic curve for the prediction of clinical pregnancy rates, the Cu/Zn ratio (AUC 0.64, 95% CI 0.54-0.71) was a better predictor than copper or zinc. When we set the cut-off as 1.59/1.60 for the Cu/Zn ratio, sensitivity, specificity, the positive predictive value, and negative predictive value were 0.98, 0.29, 0.71, and 0

  4. The "high solubility" definition of the current FDA Guidance on Biopharmaceutical Classification System may be too strict for acidic drugs.

    Science.gov (United States)

    Yazdanian, Mehran; Briggs, Katherine; Jankovsky, Corinne; Hawi, Amale

    2004-02-01

    The purpose of this study was to assess if the definition of high solubility as proposed in the FDA Guidance on Biopharmaceutical Classification System (BCS) is too strict for highly permeable acidic drugs. The solubility and permeability values of 20 (18 acidic and 2 non-acidic) nonsteroidal anti-inflammatory drugs (NSAID) were determined. The NSAIDs were grouped into three different sets having acetic acid, propionic acid, or other acidic moieties such as fenamate, oxicam, and salicylate. Two nonacidic NSAIDs (celecoxib and rofecoxib) were also included for comparison purposes. Equilibrium solubility values were determined at pH 1.2, 5.0, 7.4, and in biorelevant media simulating fed intestinal fluid at pH 5.0. For a select number of acids, we also measured solubility values in media simulating gastric and fasted intestinal fluids. Permeability classification was established relative to that of reference drugs in the Caco-2 cell permeability model. Permeability coefficients for all drugs were measured at concentrations corresponding to the lowest and highest marketed dose strengths dissolved in 250 ml volume, and their potential interaction with cellular efflux pumps was investigated. All NSAIDs with different acidic functional groups were classified as highly permeable based on their Caco-2 cell permeability. Only ketorolac appeared to have a potential for interaction with cellular efflux pumps. Solubility classification was based on comparison of equilibrium solubility at pH 1.2, 5.0. and 7.4 relative to marketed dose strengths in 250 ml. The pKa values for the acidic NSAIDs studied were between 3.5 and 5.1. and, as expected, their solubility increased dramatically at pH 7.4 compared to pH 1.2. Only three NSAIDs, ketorolac, ketoprofen. and acetyl salicylic acid, meet the current criteria for high solubility over the entire pH range. However, with the exception of ibuprofen, oxaprozin, and mefenamic acid, the remaining compounds can be classified as Class I drugs

  5. Comparison of two extraction procedures for determination of drugs of abuse in human saliva by high-performance liquid chromatography.

    Science.gov (United States)

    Fernández, P; Morales, L; Vázquez, C; Lago, M; Bermejo, A M

    2008-11-01

    High performance liquid chromatography in combination with diode array detection (HPLC-DAD) was used to determine morphine, 6-acetylmorphine, cocaine, benzoylecgonine, cocaethylene, methadone and 2-ethylene-1,5-dimethyl-3,3,-diphenylpyrrolidine in human saliva. For comparison, samples were prepared by either liquid-liquid extraction in Toxitubes A or microwave-assisted extraction (MAE), by mixing 1 ml of saliva with 10 ml of chloroform and operating at 100 degrees C for 10 min. Acetonitrile and 0.02 m phosphate buffer at pH 6.5 were used as mobile phase in HPLC in gradient mode. The detector response was linear over the drug concentration range of 0.05-2.0 microg ml(-1) in human saliva. The analytical method was validated by determining its precision and accuracy (n = 5), which were lower than 5% as relative standard deviation and 6% as relative error. Limits of detection ranged from 10 to 35 ng ml(-1); mean recoveries of drugs were from 53 to 95% with Toxitubes A and from 83 to 100% with MAE at two different concentrations (0.1 and 1.0 microg ml(-1)). The proposed method was applied to 24 saliva samples from individuals poisoned with opiates and/or cocaine.

  6. Highly Stable Operation of Lithium Metal Batteries Enabled by the Formation of a Transient High Concentration Electrolyte Layer

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Jianming; Yan, Pengfei; Mei, Donghai; Engelhard, Mark H.; Cartmell, Samuel S.; Polzin, Bryant; Wang, Chong M.; Zhang, Jiguang; Xu, Wu

    2016-02-08

    Lithium (Li) metal has been extensively investigated as an anode for rechargeable battery applications due to its ultrahigh specific capacity and the lowest redox potential. However, significant challenges including dendrite growth and low Coulombic efficiency are still hindering the practical applications of rechargeable Li metal batteries. Here, we demonstrate that long-term cycling of Li metal batteries can be realized by the formation of a transient high concentration electrolyte layer near the surface of Li metal anode during high rate discharge process. The highly concentrated Li+ ions in this transient layer will immediately solvate with the available solvent molecules and facilitate the formation of a stable and flexible SEI layer composed of a poly(ethylene carbonate) framework integrated with other organic/inorganic lithium salts. This SEI layer largely suppresses the corrosion of Li metal anode by free organic solvents and enables the long-term operation of Li metal batteries. The fundamental findings in this work provide a new direction for the development and operation of Li metal batteries that could be operated at high current densities for a wide range of applications.

  7. Hydrogen-bonded structure in highly concentrated aqueous LiBr solutions

    International Nuclear Information System (INIS)

    Imano, Masahiro; Kameda, Yasuo; Usuki, Takeshi; Uemura, Osamu

    2001-01-01

    Neutron diffraction measurements were carried out for H/D isotopically substituted aqueous 10, 25 and 33 mol% LiBr solutions in order to obtain structural information on the intermolecular hydrogen bonds among water molecules in highly concentrated aqueous solutions. Observed scattering cross sections for D 2 O (99.9 % D), 0 H 2 O(35.9 % D) and 0-2 H 2 O(68.0 % D) solutions were combined to deduce partial structure factors, a HH (Q), a XH (Q) and a XX (Q) (X: O, Br and Li). The least squares fitting analysis was applied to the observed partial structure factors to determine the nearest neighbor interatomic distance, root-mean-square amplitude and coordination number. Intermolecular distances, r OH =1.91(1) A, r HH =2.38(1) A and r OO =3.02(1) A, between the nearest neighbor water molecules, were obtained for the 10 mol% LiBr solution. On the other hand, the intermolecular O···H interaction was found to almost disappear in concentrated 25 and 33 mol% LiBr solutions. The result implies that the hydrogen-bonded network is completely broken in highly concentrated aqueous LiBr solutions. (author)

  8. Analysis of serotonin concentrations in human milk by high-performance liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Chiba, Takeshi; Maeda, Tomoji; Tairabune, Tomohiko; Tomita, Takashi; Sanbe, Atsushi; Takeda, Rika; Kikuchi, Akihiko; Kudo, Kenzo

    2017-03-25

    Serotonin (5-hydroxytryptamine, 5-HT) plays an important role in milk volume homeostasis in the mammary gland during lactation; 5-HT in milk may also affect infant development. However, there are few reports on 5-HT concentrations in human breast milk. To address this issue, we developed a simple method based on high-performance liquid chromatography with fluorescence detection (HPLC-FD) for measuring 5-HT concentrations in human breast milk. Breast milk samples were provided by four healthy Japanese women. Calibration curves for 5-HT in each sample were prepared with the standard addition method between 5 and 1000 ng/ml, and all had correlation coefficients >0.999. The recovery of 5-HT was 96.1%-101.0%, with a coefficient of variation of 3.39%-8.62%. The range of 5-HT concentrations estimated from the calibration curves was 11.1-51.1 ng/ml. Thus, the HPLC-FD method described here can effectively extract 5-HT from human breast milk with high reproducibility. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Tailoring Microbial Electrochemical Cells for Production of Hydrogen Peroxide at High Concentrations and Efficiencies.

    Science.gov (United States)

    Young, Michelle N; Links, Mikaela J; Popat, Sudeep C; Rittmann, Bruce E; Torres, César I

    2016-12-08

    A microbial peroxide producing cell (MPPC) for H 2 O 2 production at the cathode was systematically optimized with minimal energy input. First, the stability of H 2 O 2 was evaluated using different catholytes, membranes, and catalyst materials. On the basis of these results, a flat-plate MPPC fed continuously using 200 mm NaCl catholyte at a 4 h hydraulic retention time was designed and operated, producing H 2 O 2 for 18 days. H 2 O 2 concentration of 3.1 g L -1 H 2 O 2 with 1.1 Wh g -1 H 2 O 2 power input was achieved in the MPPC. The high H 2 O 2 concentration was a result of the optimum materials selected. The small energy input was largely the result of the 0.5 cm distance between the anode and cathode, which reduced ionic transport losses. However, >50 % of operational overpotentials were due to the 4.5-5 pH unit difference between the anode and cathode chambers. The results demonstrate that a MPPC can continuously produce H 2 O 2 at high concentration by selecting compatible materials and appropriate operating conditions. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Leaching of copper concentrates with high arsenic content in chlorine-chloride media

    International Nuclear Information System (INIS)

    Herreros, O.; Fuentes, G.; Quiroz, R.; Vinals, J.

    2003-01-01

    This work reports the results of copper concentrates leaching which have high arsenic concepts (up to 2.5%). The treatments were carried out using chlorine that forms from sodium hypochlorite and sulphuric acid. The aim of this work is to obtain a solution having high copper content 4 to 6 g/l and 5 to 7 g/l free acid in order to submit it directly to a solvent extraction stage. In addition, this solution should have minimum content of arsenic and chloride ions. To carry out this investigation, an acrylic reactor was constructed where the leaching tests were made at constant temperature in a thermostatic bath under atmospheric pressure. The concentrate samples were obtained from mineral processing plants from Antofagasta, Chile. Typical variables were studied, such as leaching agent concentration, leaching time, pulp density and temperature among others. Some of the residues were analyzed by XRD and EPS. On the other hand, the solutions were analyzed by Atomic Absorption Spectroscopy. The results indicate solutions having the contents stated above can be obtained. (Author) 19 refs

  11. Research on high-temperature heat receiver in concentrated solar radiation system

    Directory of Open Access Journals (Sweden)

    Estera Przenzak

    2017-01-01

    Full Text Available The article presents the results of experimental and computer simulations studies of the high temperature heat receiver working in the concentrated solar radiation system. In order to study the radiation absorption process and heat exchange, the two types of computer simulations were carried out. The first one was used to find the best location for absorber in the concentrating installation. Ray Tracing Monte Carlo (RTMC method in Trace Pro software was used to perform the optical simulations. The results of these simulations were presented in the form of the solar radiation distribution map and chart. The data obtained in RTMC simulations were used as a second type boundary conditions for Computational Fluid Dynamics (CFD simulations. These studies were used to optimize the internal geometry of the receiver and also to select the most effective flow parameters of the working medium. In order to validate the computer simulations, high temperature heat receiver was tested in experimental conditions. The article presents the results of experimental measurements in the form of temperature, radiation intensity and power graphs. The tests were performed for varied flow rate and receiver location. The experimental and computer simulation studies presented in this article allowed to optimize the configuration of concentrating and heat receiving system.

  12. Comparison of concentrations of drugs between blood samples with and without fluoride additive-important findings for Δ9-tetrahydrocannabinol and amphetamine.

    Science.gov (United States)

    Wiedfeld, Christopher; Krueger, Julia; Skopp, Gisela; Musshoff, Frank

    2018-02-17

    Fluoride is a common stabilizing agent in forensic toxicology to avoid the frequent problem of degradation of drugs in blood samples especially described for cocaine. In cases only samples with addition of fluoride are available, it is a crucial question if also concentrations of common drugs other than cocaine (amphetamines, opiates and cannabinoids) are affected by fluoride. So far, there are only rare literature data available on discrepant results especially for Δ 9 -tetrahydrocannabinol (THC). In this study, comparative analysis of positive tested paired routine plasma/serum samples (n = 375), collected at the same time point (one device with and one without fluoride), was carried out with special focus on cannabinoids. Samples were measured with validated routine liquid chromatography-tandem mass spectrometry methods for THC, 11-hydroxy-THC (THC-OH), 11-nor-9-carboxy-THC (THC-COOH), cocaine, benzoylecgonine, ecgonine methyl ester, morphine, codeine, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, and 3,4-methylenedioxyethylamphetamine, and results were statistically evaluated. Beside the expected stabilization effect on cocaine and the consequently reduced concentration of ecgonine methyl ester in fluoride samples, benzoylecgonine was elevated compared to respective samples without fluoride. Most importantly, new findings were significantly reduced mean concentrations of THC (- 17%), THC-OH (- 17%), and THC-COOH (- 22%) in fluoride samples. Mean amphetamine concentration was significantly higher in samples with the additive (+ 6%). For the other amphetamine type of drugs as well as for morphine and codeine, no significant differences could be seen. Whenever specified thresholds have been set, such as in most European countries, the use of different blood sample systems may result in a motorist being differently charged or prosecuted. The findings will support forensic toxicologists at the

  13. 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

  14. [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.

  15. High Efficiency Nanostructured III-V Photovoltaics for Solar Concentrator Application

    Energy Technology Data Exchange (ETDEWEB)

    Hubbard, Seth

    2012-09-12

    The High Efficiency Nanostructured III-V Photovoltaics for Solar Concentrators project seeks to provide new photovoltaic cells for Concentrator Photovoltaics (CPV) Systems with higher cell efficiency, more favorable temperature coefficients and less sensitivity to changes in spectral distribution. The main objective of this project is to provide high efficiency III-V solar cells that will reduce the overall cost per Watt for power generation using CPV systems.This work is focused both on a potential near term application, namely the use of indium arsenide (InAs) QDs to spectrally "tune" the middle (GaAs) cell of a SOA triple junction device to a more favorable effective bandgap, as well as the long term goal of demonstrating intermediate band solar cell effects. The QDs are confined within a high electric field i-region of a standard GaAs solar cell. The extended absorption spectrum (and thus enhanced short circuit current) of the QD solar cell results from the increase in the sub GaAs bandgap spectral response that is achievable as quantum dot layers are introduced into the i-region. We have grown InAs quantum dots by OMVPE technique and optimized the QD growth conditions. Arrays of up to 40 layers of strain balanced quantum dots have been experimentally demonstrated with good material quality, low residual stain and high PL intensity. Quantum dot enhanced solar cells were grown and tested under simulated one sun AM1.5 conditions. Concentrator solar cells have been grown and fabricated with 5-40 layers of QDs. Testing of these devices show the QD cells have improved efficiency compared to baseline devices without QDs. Device modeling and measurement of thermal properties were performed using Crosslight APSYS. Improvements in a triple junction solar cell with the insertion of QDs into the middle current limiting junction was shown to be as high as 29% under one sun illumination for a 10 layer stack QD enhanced triple junction solar cell. QD devices have strong

  16. Reduced antituberculosis drug concentrations in HIV-infected patients who are men or have low weight: implications for international dosing guidelines.

    Science.gov (United States)

    McIlleron, Helen; Rustomjee, Roxana; Vahedi, Mahnaz; Mthiyane, Thuli; Denti, Paolo; Connolly, Catherine; Rida, Wasima; Pym, Alexander; Smith, Peter J; Onyebujoh, Philip C

    2012-06-01

    Reduced antituberculosis drug concentrations may contribute to unfavorable treatment outcomes among HIV-infected patients with more advanced immune suppression, and few studies have evaluated pharmacokinetics of the first-line antituberculosis drugs in such patients given fixed-dose combination tablets according to international guidelines using weight bands. In this study, pharmacokinetics were evaluated in 60 patients on 4 occasions during the first month of antituberculosis therapy. Multilevel linear mixed-effects regression analysis was used to examine the effects of age, sex, weight, drug dose/kilogram, CD4(+) lymphocyte count, treatment schedule (5 versus 7 days/week), and concurrent antiretrovirals (efavirenz plus lamivudine plus zidovudine) on the area under the concentration-time curve from 0 to 12 h (AUC(0-12)) of the respective antituberculosis drugs and to compare AUC(0-12)s at day 8, day 15, and day 29 with the day 1 AUC(0-12). Median (range) age, weight, and CD4(+) lymphocyte count were 32 (18 to 47) years, 55.2 (34.4 to 98.7) kg, and 252 (12 to 500)/μl. For every 10-kg increase in body weight, the predicted day 29 AUC(0-12) increased by 14.1% (95% confidence interval [CI], 7.5, 20.8), 14.1% (95% CI, -0.7, 31.1), 6.1% (95% CI, 2.7, 9.6) and 6.0% (95% CI, 0.8, 11.3) for rifampin, isoniazid, pyrazinamide, and ethambutol, respectively. Males had day 29 AUC(0-12)s 19.3% (95% CI, 3.6, 35.1) and 14.0% (95% CI, 5.6, 22.4) lower than females for rifampin and pyrazinamide, respectively. Level of immune suppression and concomitant antiretrovirals had little effect on the concentrations of the antituberculosis agents. As they had reduced drug concentrations, it is important to review treatment responses in patients in the lower weight bands and males to inform future treatment guidelines, and revision of doses in these patients should be considered.

  17. Process evaluation of enzymatic hydrolysis with filtrate recycle for the production of high concentration sugars.

    Science.gov (United States)

    Xue, Ying; Rusli, Jannov; Chang, Hou-Min; Phillips, Richard; Jameel, Hasan

    2012-02-01

    Process simulation and lab trials were carried out to demonstrate and confirm the efficiency of the concept that recycling hydrolysate at low total solid enzymatic hydrolysis is one of the options to increase the sugar concentration without mixing problems. Higher sugar concentration can reduce the capital cost for fermentation and distillation because of smaller retention volume. Meanwhile, operation cost will also decrease for less operating volume and less energy required for distillation. With the computer simulation, time and efforts can be saved to achieve the steady state of recycling process, which is the scenario for industrial production. This paper, to the best of our knowledge, is the first paper discussing steady-state saccharification with recycling of the filtrate form enzymatic hydrolysis to increase sugar concentration. Recycled enzymes in the filtrate (15-30% of the original enzyme loading) resulted in 5-10% higher carbohydrate conversion compared to the case in which recycled enzymes were denatured. The recycled hydrolysate yielded 10% higher carbohydrate conversion compared to pure sugar simulated hydrolysate at the same enzyme loading, which indicated hydrolysis by-products could boost enzymatic hydrolysis. The high sugar concentration (pure sugar simulated) showed inhibition effect, since about 15% decrease in carbohydrate conversion was observed compared with the case with no sugar added. The overall effect of hydrolysate recycling at WinGEMS simulated steady-state conditions with 5% total solids was increasing the sugar concentration from 35 to 141 g/l, while the carbohydrate conversion was 2% higher for recycling at steady state (87%) compared with no recycling strategy (85%). Ten percent and 15% total solid processes were also evaluated in this study.

  18. Bleaching and enamel surface interactions resulting from the use of highly-concentrated bleaching gels.

    Science.gov (United States)

    Grazioli, Guillermo; Valente, Lisia Lorea; Isolan, Cristina Pereira; Pinheiro, Helena Alves; Duarte, Camila Gonçalves; Münchow, Eliseu Aldrighi

    2018-03-01

    Tooth bleaching is considered a non-invasive treatment, although the use of highly-concentrated products may provoke increased surface roughness and enamel demineralization, as well as postoperative sensitivity. Thus, the aim of this study was to investigate whether hydrogen peroxide (H 2 O 2 ) concentration would affect tooth bleaching effectiveness and the enamel surface properties. Enamel/dentin bovine specimens (6 × 4 mm) were immersed in coffee solution for 7 days and evaluated with a spectrophotometer (Easyshade; baseline), using the CIEL * a * b * color parameters. Hardness was measured using a hardness tester. The specimens were randomly assigned into four groups: one negative control, in which the specimens were not bleached, but they were irradiated with a laser-light source (Whitening Lase II, DMC Equipments); and three groups using distinct H 2 O 2 concentration, namely LP15% (15% Lase Peroxide Lite), LP25% (25% Lase Peroxide Sensy), and LP35% (35% Lase Peroxide Sensy), all products from DMC. The bleached specimens were also irradiated with the laser-light source. After bleaching, all specimens were evaluated using scanning electron microscopy (SEM). pH kinetics and rate was monitored during bleaching. The data were analyzed using ANOVA and Tukey's test (p bleaching gels produced similar color change (p > 0.05). Concerning hardness, only the LP25% and LP35% significantly reduced hardness after bleaching; also, there was a progressive tendency for a greater percentage reduction in hardness with increased H 2 O 2 concentration of the gel (R 2  = 0.9973, p bleaching effectiveness, and may increase the possibility for alteration of enamel hardness, surface morphology, and acidity of the medium. When using H 2 O 2 -based bleaching agents, dental practitioners should choose for less concentrated gels, e.g., around the 15% level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Diagnostic of N2(A) concentration in high velocity nitrogen afterglow at atmospheric pressure

    Science.gov (United States)

    Pointu, Anne-Marie; Mintusov, Evgeny

    2009-10-01

    An optical emission diagnostic was used to measure N2(A) concentration in a high velocity (1000 cm/s) N2 flowing afterglow of corona discharge at atmospheric pressure, used for biological decontamination. Introducing impurities of NO (measured at different axial distances and for different values of NO injected flow. Moreover, it has been demonstrated that N2(A) creation comes from N+N+N2 atom recombination with a global rate around 2e-33 cm^6/s, a result which agrees with literature, as well as N2(A) loss mechanisms were confirmed to go via quenching with O and N atoms. The order of magnitude of obtained N2(A) concentration, about 1e11 cm-3, coincides with the results of direct measurement (by Vegard-Kaplan band), using a spectrometer of better resolution.

  20. Carbon dioxide as working fluid for medium and high-temperature concentrated solar thermal systems

    Directory of Open Access Journals (Sweden)

    Van Duong

    2014-03-01

    Full Text Available This paper explores the benefits and drawbacks of using carbon dioxide in solar thermal systems at medium and high operating temperatures. For medium temperatures, application of CO2 in non-imaging-optics based compound parabolic concentrators (CPC combined with evacuated-tube collectors is studied. These collectors have been shown to obtain efficiencies higher than 40% operating at around 200℃ without the need of tracking. Validated numerical models of external compound parabolic concentrators (XCPCs are used to simulate their performance using CO2 as working fluid. For higher temperatures, a mathematical model is implemented to analyze the operating performance of a parabolic trough solar collector (PTC using CO2 at temperatures between 100℃ and 600℃.

  1. Phenomenon of energy concentration in high-energy family events of cosmic rays

    CERN Document Server

    Wang He; Dai Zhi Qiang; Xue Liang; Feng Cun Feng; Zhang Xue Yao; Li Jin; Zhang Nai Jian; He Mao; Wang Cheng Rui; Ren Jing Ru; Lu Sui Ling

    2002-01-01

    The phenomenon of energy concentration in high-energy family events of cosmic rays is studied by comparing the results of family events of total visible energies 100-400 TeV observed in the Kanbala emulsion chamber experiment with the Monte Carlo simulation data. The simulation is made by the program CORSIKA in which QGSJET is applied as the hadronic interaction model, and the chemical composition of primary cosmic rays is obtained from the rigidity-cut model and the extrapolation of new results of direct measurements. This shows that the whole distribution tendency of the rate of energy concentration of simulated family events is basically consistent with that of the experiment

  2. Green synthesis of highly concentrated aqueous colloidal solutions of large starch-stabilised silver nanoplatelets.

    Science.gov (United States)

    Cheng, Fei; Betts, Jonathan W; Kelly, Stephen M; Hector, Andrew L

    2015-01-01

    A simple, environmentally friendly and cost-effective method has been developed to prepare a range of aqueous silver colloidal solutions, using ascorbic acid as a reducing agent, water-soluble starch as a combined crystallising, stabilising and solubilising agent, and water as the solvent. The diameter of silver nanoplatelets increases with higher concentrations of AgNO3 and starch. The silver nanoparticles are also more uniform in shape the greater the diameter of the nanoparticles. Colloidal solutions with a very high concentration of large, flat, hexagonal silver nanoplatelets (~230 nm in breadth) have been used to deposit and fix an antibacterial coating of these large starch-stabilised silver nanoplates on commercial cotton fibres, using a simple dip-coating process using water as the solvent, in order to study the dependence of the antibacterial properties of these nanoplatelets on their size. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. AIDS Diarrhea and Antiretroviral Drug Concentrations: A Matched-Pair Cohort Study in Port au Prince, Haiti

    Science.gov (United States)

    Dillingham, Rebecca; Leger, Paul; Beauharnais, Carole-Anne; Miller, Erica; Kashuba, Angela; Jennings, Steven; Dupnik, Kathryn; Samie, Amidou; Eyma, Etna; Guerrant, Richard; Pape, Jean; Fitzgerald, Daniel

    2011-01-01

    Diarrhea in patients with acquired immunodeficiency syndrome (AIDS) may cause malabsorption of medications and failure of antiretroviral therapy (ART). We prospectively evaluated human immunodeficiency virus-1 (HIV-1)-infected patients with and without chronic diarrhea initiating ART in Haiti. We report mean plasma antiretroviral concentrations at 2 and 4 weeks. We measured plasma HIV-1 RNA levels at four points. Fifty-two HIV-1-infected patients (26 matched pairs) were enrolled. No differences in antiretroviral concentrations were detected. At week 24, 18/25 (72%) cases and 16/24 (68%) controls had undetectable plasma HIV-1 RNA levels (P = 0.69). Patients with plasma HIV-1 RNA levels > 50 copies/mL at week 24 had lower early efavirenz concentrations than patients with undetectable HIV-1 RNA (2,621 ng/mL versus 5,278 ng/mL; P = 0.02). Diarrhea at ART initiation does not influence plasma concentrations of the medications evaluated. Virologic outcome at Week 24 does correlate with efavirenz concentrations early in therapy but not with the presence of chronic diarrhea. PMID:21633022

  4. Observations of high droplet number concentrations in Southern Ocean boundary layer clouds

    Directory of Open Access Journals (Sweden)

    T. Chubb

    2016-01-01

    Full Text Available Cloud physics data collected during the NSF/NCAR High-performance Instrumented Airborne Platform for Environmental Research (HIAPER Pole-to-Pole Observations (HIPPO campaigns provide a snapshot of unusual wintertime microphysical conditions in the boundary layer over the Southern Ocean. On 29 June 2011, the HIAPER sampled the boundary layer in a region of pre-frontal warm air advection between 58 and 48° S to the south of Tasmania. Cloud droplet number concentrations were consistent with climatological values in the northernmost profiles but were exceptionally high for wintertime in the Southern Ocean at 100–200 cm−3 in the southernmost profiles. Sub-micron (0.06  < D <  1 µm aerosol concentrations for the southern profiles were up to 400 cm−3. Analysis of back trajectories and atmospheric chemistry observations revealed that while conditions in the troposphere were more typical of a clean remote ocean airmass, there was some evidence of continental or anthropogenic influence. However, the hypothesis of long-range transport of continental aerosol fails to explain the magnitude of the aerosol and cloud droplet concentration in the boundary layer. Instead, the gale force surface winds in this case (wind speed at 167 m above sea level was  > 25 m s−1 were most likely responsible for production of sea spray aerosol which influenced the microphysical properties of the boundary layer clouds. The smaller size and higher number concentration of cloud droplets is inferred to increase the albedo of these clouds, and these conditions occur regularly, and are expected to increase in frequency, over windy parts of the Southern Ocean.

  5. The salivary microbiome is altered in the presence of a high salivary glucose concentration.

    Directory of Open Access Journals (Sweden)

    J Max Goodson

    Full Text Available Type II diabetes (T2D has been associated with changes in oral bacterial diversity and frequency. It is not known whether these changes are part of the etiology of T2D, or one of its effects.We measured the glucose concentration, bacterial counts, and relative frequencies of 42 bacterial species in whole saliva samples from 8,173 Kuwaiti adolescents (mean age 10.00 ± 0.67 years using DNA probe analysis. In addition, clinical data related to obesity, dental caries, and gingivitis were collected. Data were compared between adolescents with high salivary glucose (HSG; glucose concentration ≥ 1.0 mg/d, n = 175 and those with low salivary glucose (LSG, glucose concentration < 0.1 mg/dL n = 2,537.HSG was associated with dental caries and gingivitis in the study population. The overall salivary bacterial load in saliva decreased with increasing salivary glucose concentration. Under HSG conditions, the bacterial count for 35 (83% of 42 species was significantly reduced, and relative bacterial frequencies in 27 species (64% were altered, as compared with LSG conditions. These alterations were stronger predictors of high salivary glucose than measures of oral disease, obesity, sleep or fitness.HSG was associated with a reduction in overall bacterial load and alterations to many relative bacterial frequencies in saliva when compared with LSG in samples from adolescents. We propose that hyperglycemia due to obesity and/or T2D results in HSG and subsequent acidification of the oral environment, leading to a generalized perturbation in the oral microbiome. This suggests a basis for the observation that hyperglycemia is associated with an increased risk of dental erosion, dental caries, and gingivitis. We conclude that HSG in adolescents may be predicted from salivary microbial diversity or frequency, and that the changes in the oral microbial composition seen in adolescents with developing metabolic disease may the consequence of hyperglycemia.

  6. Root based responses account for Psidium guajava survival at high nickel concentration.

    Science.gov (United States)

    Bazihizina, Nadia; Redwan, Mirvat; Taiti, Cosimo; Giordano, Cristiana; Monetti, Emanuela; Masi, Elisa; Azzarello, Elisa; Mancuso, Stefano

    2015-02-01

    The presence of Psidium guajava in polluted environments has been reported in recent studies, suggesting that this species has a high tolerance to the metal stress. The present study aims at a physiological characterization of P. guajava response to high nickel (Ni) concentrations in the root-zone. Three hydroponic experiments were carried out to characterize the effects of toxic Ni concentrations on morphological and physiological parameters of P. guajava, focusing on Ni-induced damages at the root-level and root ion fluxes. With up to 300μM NiSO4 in the root-zone, plant growth was similar to that in control plants, whereas at concentrations higher than 1000μM NiSO4 there was a progressive decline in plant growth and leaf gas exchange parameters; this occurred despite, at all considered concentrations, plants limited Ni(2+) translocation to the shoot, therefore avoiding shoot Ni(2+) toxicity symptoms. Maintenance of plant growth with 300μM Ni(2+) was associated with the ability to retain K(+) in the roots meanwhile 1000 and 3000μM NiSO4 led to substantial K(+) losses. In this study, root responses mirror all plant performances suggesting a direct link between root functionality and Ni(2+) tolerance mechanisms and plant survival. Considering that Ni was mainly accumulated in the root system, the potential use of P. guajava for Ni(2+) phytoextraction in metal-polluted soils is limited; nevertheless, the observed physiological changes indicate a good Ni(2+) tolerance up to 300μM NiSO4 suggesting a potential role for the phytostabilization of polluted soils. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. High Ice Water Concentrations in the 19 August 2015 Coastal Mesoconvective System

    Science.gov (United States)

    Proctor, Fred H.; Harrah, Steven; Switzer, George F.; Strickland, Justin K.; Hunt, Patricia J.

    2017-01-01

    During August 2015, NASA's DC-8 research aircraft was flown into High Ice Water Content (HIWC) events as part of a three-week campaign to collect airborne radar data and to obtain measurements from microphysical probes. Goals for this flight campaign included improved characterization of HIWC events, especially from an airborne radar perspective. This paper focuses on one of the flight days, in which a coastal mesoscale convective system (MCS) was investigated for HIWC conditions. The system appears to have been maintained by bands of convection flowing in from the Gulf of Mexico. These convective bands were capped by a large cloud canopy, which masks the underlying structure if viewed from an infrared sensing satellite. The DC-8 was equipped with an IsoKinetic Probe that measured ice concentrations of up to 2.3 g m(exp -3) within the cloud canopy of this system. Sustained measurements of ice crystals with concentrations exceeding 1 g m(exp -3) were encountered for up to ten minutes of flight time. Airborne Radar reflectivity factors were found to be weak within these regions of high ice water concentrations, suggesting that Radar detection of HIWC would be a challenging endeavor. This case is then investigated using a three-dimensional numerical cloud model. Profiles of ice water concentrations and radar reflectivity factor demonstrate similar magnitudes and scales between the flight measurements and model simulation. Also discussed are recent modifications to the numerical model's ice-microphysics that are based on measurements during the flight campaign. The numerical model and its updated ice-microphysics are further validated with a simulation of a well-known case of a supercell hailstorm measured during the Cooperative Convective Precipitation Experiment. Differences in HIWC between the continental supercell and the coastal MCS are discussed.

  8. Use of high concentrations of carbon dioxide for stunning rabbits reared for meat production

    Directory of Open Access Journals (Sweden)

    A. Dalmau

    2016-03-01

    Full Text Available Abstract: An investigation was performed to determine whether high concentrations of carbon dioxide (CO2 at 70-98% in atmospheric air are a suitable alternative for stunning rabbits compared to conventional approaches such as electronarcosis. Aversion to the gas and efficacy in causing prolonged unconsciousness and death were studied in a total of 480 rabbits by means of behavioural parameters, physiological indicators (presence of rhythmic breathing and corneal reflex and electroencephalography (EEG, brain function. The use of any of the 4 studied concentrations of the gas caused more nasal discomfort and vocalisations than the use of atmospheric air (P<0.001. EEG activity confirmed that loss of posture is a good indicator of the onset of unconsciousness in rabbits exposed to CO2, occurring earlier (P<0.05 at 90 and 98% than at 70 and 80%. Rabbits showed signs of aversion for 15 s before the onset of unconsciousness, which occurred around 30 s after the beginning of the exposure to the gas, similar to species such as swine in which high concentrations of CO2 are also used for stunning. CO2 at 80 to 98% is suggested as a reasonable concentration range to induce a long state of unconsciousness and death in rabbits, while 70% CO2 is not recommended because it requires too long duration of exposure (more than 360 s to ensure effectiveness. Despite the advantages in terms of pre-stun handling and irreversibility, CO2 is not free of animal welfare concerns. In consequence, a debate is necessary to ascertain if CO2 can be considered a suitable alternative to stun rabbits, considering the advantages and drawbacks cited, quantified in the present study as 15 s of aversion (nasal discomfort and vocalisations before losing posture.

  9. Factors affecting biotic mercury concentrations and biomagnification through lake food webs in the Canadian high Arctic

    Energy Technology Data Exchange (ETDEWEB)

    Lescord, Gretchen L., E-mail: glescord@gmail.com [University of New Brunswick/Canadian Rivers Institute, 100 Tucker Park Rd, Saint John, NB E2L 4A6 (Canada); Kidd, Karen A. [University of New Brunswick/Canadian Rivers Institute, 100 Tucker Park Rd, Saint John, NB E2L 4A6 (Canada); Kirk, Jane L. [Environment Canada, Aquatic Contaminants Research Division, 867 Lakeshore Rd, Burlington, ON L7S 1A1 (Canada); O' Driscoll, Nelson J. [Acadia University, 15 University Ave, Wolfville, NS B4P 2R6 (Canada); Wang, Xiaowa; Muir, Derek C.G. [Environment Canada, Aquatic Contaminants Research Division, 867 Lakeshore Rd, Burlington, ON L7S 1A1 (Canada)

    2015-03-15

    In temperate regions of Canada, mercury (Hg) concentrations in biota and the magnitude of Hg biomagnification through food webs vary between neighboring lakes and are related to water chemistry variables and physical lake features. However, few studies have examined factors affecting the variable Hg concentrations in landlocked Arctic char (Salvelinus alpinus) or the biomagnification of Hg through their food webs. We estimated the food web structure of six high Arctic lakes near Resolute Bay, Nunavut, Canada, using stable carbon (δ{sup 13}C) and nitrogen (δ{sup 15}N) isotopes and measured Hg (total Hg (THg) in char, the only fish species, and methylmercury (MeHg) in chironomids and zooplankton) concentrations in biota collected in 2010 and 2011. Across lakes, δ{sup 13}C showed that benthic carbon (chironomids) was the dominant food source for char. Regression models of log Hg versus δ{sup 15}N (of char and benthic invertebrates) showed positive and significant slopes, indicting Hg biomagnification in all lakes, and higher slopes in some lakes than others. However, no principal components (PC) generated using all water chemistry data and physical characteristics of the lakes predicted the different slopes. The PC dominated by aqueous ions was a negative predictor of MeHg concentrations in chironomids, suggesting that water chemistry affects Hg bioavailability and MeHg concentrations in these lower-trophic-level organisms. Furthermore, regression intercepts were predicted by the PCs dominated by catchment area, aqueous ions, and MeHg. Weaker relationships were also found between THg in small char or MeHg in pelagic invertebrates and the PCs dominated by catchment area, and aqueous nitrate and MeHg. Results from these high Arctic lakes suggest that Hg biomagnification differs between systems and that their physical and chemical characteristics affect Hg concentrations in lower-trophic-level biota. - Highlights: • Mercury (Hg) in Arctic char and invertebrates

  10. Reactive Transport Modeling Investigation of High Dissolved Sulfide Concentrations in Sedimentary Basin Rocks

    Science.gov (United States)

    Xie, M.; Mayer, U. K.; MacQuarrie, K. T. B.

    2017-12-01

    Water with total dissolved sulfide in excess of 1 mmol L-1is widely found in groundwater at intermediate depths in sedimentary basins, including regions of the Michigan basin in southeastern Ontario, Canada. Conversely, at deeper and shallower depths, relatively low total dissolved sulfide concentrations have been reported. The mechanisms responsible for the occurrence of these brackish sulfide-containing waters are not fully understood. Anaerobic microbial sulfate reduction is a common process resulting in the formation of high sulfide concentrations. Sulfate reduction rates depend on many factors including the concentration of sulfate, the abundance of organic substances, redox conditions, temperature, salinity and the species of sulfate reducing bacteria (SRB). A sedimentary basin-specific conceptual model considering the effect of salinity on the rate of sulfate reduction was developed and implemented in the reactive transport model MIN3P-THCm. Generic 2D basin-scale simulations were undertaken to provide a potential explanation for the dissolved sulfide distribution observed in the Michigan basin. The model is 440 km in the horizontal dimension and 4 km in depth, and contains fourteen sedimentary rock units including shales, sandstones, limestones, dolostone and evaporites. The main processes considered are non-isothermal density dependent flow, kinetically-controlled mineral dissolution/precipitation and its feedback on hydraulic properties, cation exchange, redox reactions, biogenic sulfate reduction, and hydromechanical coupling due to glaciation-deglaciation events. Two scenarios were investigated focusing on conditions during an interglacial period and the transient evolution during a glaciation-deglaciation cycle. Inter-glaciation simulations illustrate that the presence of high salinity brines strongly suppress biogenic sulfate reduction. The transient simulations show that glaciation-deglaciation cycles can have an impact on the maximum depth of

  11. Anaerobic treatment of wastewater with high suspended solids from a bulk drug industry using fixed film reactor (AFFR).

    Science.gov (United States)

    Gangagni Rao, A; Venkata Naidu, G; Krishna Prasad, K; Chandrasekhar Rao, N; Venkata Mohan, S; Jetty, Annapurna; Sarma, P N

    2005-01-01

    Studies were carried out on the treatment of wastewater from a bulk drug industry using an anaerobic fixed film reactor (AFFR) designed and fabricated in the laboratory. The chemical oxygen demand (COD) and total dissolved solids (TDS) of the wastewater were found to be very high with low biochemical oxygen demand (BOD) to COD ratio and high total suspended solid (TSS) concentration. Acclimatization of seed consortia and startup of the reactor was carried out by directly using the wastewater, which resulted in reducing the period of startup to 30 days. The reactor was studied at different organic loading rates (OLR) and it was found that the optimum OLR was 10 kg COD/m(3)/day. The wastewater under investigation, which had a considerable quantity of SS, was treated anaerobically without any pretreatment. COD and BOD of the reactor outlet wastewater were monitored and at steady state and optimum OLR 60-70% of COD and 80-90% of BOD were removed. The reactor was subjected to organic shock loads at two different OLR and the reaction could withstand the shocks and performance could be restored to normalcy at that OLR. The results obtained indicated that AFFR could be used efficiently for the treatment of wastewater from a bulk drug industry having high COD, TDS and TSS.

  12. Solution Behavior and Activity of a Halophilic Esterase under High Salt Concentration

    Science.gov (United States)

    Rao, Lang; Zhao, Xiubo; Pan, Fang; Li, Yin; Xue, Yanfen; Ma, Yanhe; Lu, Jian R.

    2009-01-01

    Background Halophiles are extremophiles that thrive in environments with very high concentrations of salt. Although the salt reliance and physiology of these extremophiles have been widely investigated, the molecular working mechanisms of their enzymes under salty conditions have been little explored. Methodology/Principal Findings A halophilic esterolytic enzyme LipC derived from archeaon Haloarcula marismortui was overexpressed from Escherichia coli BL21. The purified enzyme showed a range of hydrolytic activity towards the substrates of p-nitrophenyl esters with different alkyl chains (n = 2−16), with the highest activity being observed for p-nitrophenyl acetate, consistent with the basic character of an esterase. The optimal esterase activities were found to be at pH 9.5 and [NaCl] = 3.4 M or [KCl] = 3.0 M and at around 45°C. Interestingly, the hydrolysis activity showed a clear reversibility against changes in salt concentration. At the ambient temperature of 22°C, enzyme systems working under the optimal salt concentrations were very stable against time. Increase in temperature increased the activity but reduced its stability. Circular dichroism (CD), dynamic light scattering (DLS) and small angle neutron scattering (SANS) were deployed to determine the physical states of LipC in solution. As the salt concentration increased, DLS revealed substantial increase in aggregate sizes, but CD measurements revealed the maximal retention of the α-helical structure at the salt concentration matching the optimal activity. These observations were supported by SANS analysis that revealed the highest proportion of unimers and dimers around the optimal salt concentration, although the coexistent larger aggregates showed a trend of increasing size with salt concentration, consistent with the DLS data. Conclusions/Significance The solution α-helical structure and activity relation also matched the highest proportion of enzyme unimers and dimers. Given that

  13. 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

  14. Relationship between self-reported adherence, antiretroviral drug concentration measurement and self-reported symptoms in patients treated for HIV-1 infection.

    Science.gov (United States)

    Fabbiani, Massimiliano; Di Giambenedetto, Simona; Cingolani, Antonella; Fanti, Iuri; Colafigli, Manuela; Tamburrini, Enrica; Cauda, Roberto; Navarra, Pierluigi; De Luca, Andrea; Murri, Rita

    2016-01-01

    The aim of the study was to explore relationships between self-reported adherence, antiretroviral drug concentration measurement (TDM) and self-reported symptoms. We systematically administered to human immunodeficiency (HIV)-infected outpatients a questionnaire evaluating measures of self-reported adherence (missing doses during last week, deviations from the prescribed timing of therapy, self-initiated discontinuations for > 24 or 48 h, exhausting drugs and present sense of how patients are taking therapy) and a panel of referred symptoms (a symptom score was built summing self-reported scores for each listed symptom). We selected patients who completed the questionnaire and also had a TDM (mainly reflecting adherence in the past few days or weeks), thus comparing these two tools as measures of adherence. A total of 130 patients (64.6% males, median age 44 years, 76.2% with HIV RNA HIV RNA symptom score was associated with a lower self-reported adherence and with a higher proportion of undetectable drug levels. Self-reported adherence and TDM showed a correlation and seemed to be comparable tools for adherence estimation. Self-reported symptoms were associated with lower adherence and undetectable drug levels.

  15. 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.

  16. Soil and Water Assessment Tool model predictions of annual maximum pesticide concentrations in high vulnerability watersheds.

    Science.gov (United States)

    Winchell, Michael F; Peranginangin, Natalia; Srinivasan, Raghavan; Chen, Wenlin

    2018-05-01

    Recent national regulatory assessments of potential pesticide exposure of threatened and endangered species in aquatic habitats have led to increased need for watershed-scale predictions of pesticide concentrations in flowing water bodies. This study was conducted to assess the ability of the uncalibrated Soil and Water Assessment Tool (SWAT) to predict annual maximum pesticide concentrations in the flowing water bodies of highly vulnerable small- to medium-sized watersheds. The SWAT was applied to 27 watersheds, largely within the midwest corn belt of the United States, ranging from 20 to 386 km 2 , and evaluated using consistent input data sets and an uncalibrated parameterization approach. The watersheds were selected from the Atrazine Ecological Exposure Monitoring Program and the Heidelberg Tributary Loading Program, both of which contain high temporal resolution atrazine sampling data from watersheds with exceptionally high vulnerability to atrazine exposure. The model performance was assessed based upon predictions of annual maximum atrazine concentrations in 1-d and 60-d durations, predictions critical in pesticide-threatened and endangered species risk assessments when evaluating potential acute and chronic exposure to aquatic organisms. The simulation results showed that for nearly half of the watersheds simulated, the uncalibrated SWAT model was able to predict annual maximum pesticide concentrations within a narrow range of uncertainty resulting from atrazine application timing patterns. An uncalibrated model's predictive performance is essential for the assessment of pesticide exposure in flowing water bodies, the majority of which have insufficient monitoring data for direct calibration, even in data-rich countries. In situations in which SWAT over- or underpredicted the annual maximum concentrations, the magnitude of the over- or underprediction was commonly less than a factor of 2, indicating that the model and uncalibrated parameterization

  17. Technical note: False low turbidity readings from optical probes during high suspended-sediment concentrations

    Science.gov (United States)

    Voichick, Nicholas; Topping, David; Griffiths, Ronald

    2018-01-01

    Turbidity, a measure of water clarity, is monitored for a variety of purposes including (1) to help determine whether water is safe to drink, (2) to establish background conditions of lakes and rivers and detect pollution caused by construction projects and stormwater discharge, (3) to study sediment transport in rivers and erosion in catchments, (4) to manage siltation of water reservoirs, and (5) to establish connections with aquatic biological properties, such as primary production and predator–prey interactions. Turbidity is typically measured with an optical probe that detects light scattered from particles in the water. Probes have defined upper limits of the range of turbidity that they can measure. The general assumption is that when turbidity exceeds this upper limit, the values of turbidity will be constant, i.e., the probe is pegged; however, this assumption is not necessarily valid. In rivers with limited variation in the physical properties of the suspended sediment, at lower suspended-sediment concentrations, an increase in suspended-sediment concentration will cause a linear increase in turbidity. When the suspended-sediment concentration in these rivers is high, turbidity levels can exceed the upper measurement limit of an optical probe and record a constant pegged value. However, at extremely high suspended-sediment concentrations, optical turbidity probes do not necessarily stay pegged at a constant value. Data from the Colorado River in Grand Canyon, Arizona, USA, and a laboratory experiment both demonstrate that when turbidity exceeds instrument-pegged conditions, increasing suspended-sediment concentration (and thus increasing turbidity) may cause optical probes to record decreasing false turbidity values that appear to be within the valid measurement range of the probe. Therefore, under high-turbidity conditions, other surrogate measurements of turbidity (e.g., acoustic-attenuation measurements or suspended-sediment samples

  18. Preparation of a highly concentrated, completely monomeric, active sarcoplasmic reticulum Ca2+-ATPase.

    Science.gov (United States)

    Lüdi, H; Hasselbach, W

    1985-11-21

    Sarcoplasmic reticulum vesicles from fast skeletal muscle were partially delipidated with sodium cholate at high ionic strength and sedimented in a discontinuous sucrose gradient. Phospholipid content was reduced from 0.777 mumol/mg protein to 0.242 mumol/mg protein. As judged from gel electrophoresis and high pressure liquid gel chromatography, accessory proteins were removed during centrifugation and the Ca2+-ATPase was obtained in an almost pure form. Addition of myristoylglycerophosphocholine (1 mg/mg protein) reactivates ATPase and dinitrophenylphosphatase activity to the same degree obtained with native vesicles. Using the analytical ultracentrifuge it could be demonstrated that the reactivated Ca2+-ATPase was present exclusively in a monomeric state. These results were obtained at high and low ionic strength and up to a protein concentration of 10 mg/ml. Therefore this preparation should be very useful to investigate differences between oligomeric and monomeric Ca2+-ATPase.

  19. Large-area, high-intensity PV arrays for systems using dish concentrating optics

    Energy Technology Data Exchange (ETDEWEB)

    Ward, J.S.; Duda, A.; Zweibel, K.; Coutts, T.J. [National Renewable Energy Lab., Golden, CO (United States)

    1998-09-01

    In this paper, the authors report on efforts to fabricate monolithic interconnected modules (MIMs) using III-V semiconductors with bandgaps appropriate for the terrestrial solar spectrum. The small size of the component cells comprising the MIM allows for operation at extremely high flux densities and relaxes the requirement for a small spot size to be generated by the optics. This makes possible a PV option for the large dish concentrator systems that have been developed by the solar thermal community for use with Stirling engines. Additionally, the highly effective back-surface reflector integrated into the MIM design is an effective tool for thermal management of the array. Development of this technology would radically alter the projections for PV manufacturing capacity because of the potential for extremely high power generation per unit area of semiconductor material.

  20. 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

  1. Corrosion mechanism of 13Cr stainless steel in completion fluid of high temperature and high concentration bromine salt

    International Nuclear Information System (INIS)

    Liu, Yan; Xu, Lining; Lu, Minxu; Meng, Yao; Zhu, Jinyang; Zhang, Lei

    2014-01-01

    Highlights: • The corrosion behavior of 13Cr steel exposed to bromine salt completion fluid containing high concentration bromine ions was investigated. • There are passive circles around pits on the 13Cr steel surface after 7 d of exposure. • Macroscopic galvanic corrosion formed between the passive halo and the pit. • The mechanism of pitting corrosion on 13Cr stainless steel exposed to heavy bromine brine was established. - Abstract: A series of corrosion tests of 13Cr stainless steel were conducted in a simulated completion fluid environment of high temperature and high concentration bromine salt. Corrosion behavior of specimens and the component of corrosion products were investigated by means of scanning electron microscope (SEM), confocal laser scanning microscopy (CLSM) and X-ray photoelectron spectroscopy (XPS). The results indicate that 13Cr steel suffers from severe local corrosion and there is always a passive halo around every pit. The formation mechanism of the passive halo is established. OH − ligand generates and adsorbs in a certain scale because of abundant OH − on the surface around the pits. Passive film forms around each pit, which leads to the occurrence of passivation in a certain region. Finally, the dissimilarities in properties and morphologies of regions, namely the pit and its corresponding passive halo, can result in different corrosion sensitivities and may promote the formation of macroscopic galvanic pairs

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Characteristics and treatment mechanism of mine water with high concentration of iron and manganese

    Energy Technology Data Exchange (ETDEWEB)

    Li, F.; Yang, J.; He, X.; Yang, J.; Tian, T. [Hebei University of Engineering, Handan (China)

    2006-12-15

    The characteristics and treatment of mine water with high concentration or iron and manganese were studied with mine water produced in Jiukuang and Siwan belonging to Hebi Coal Industry Group Co., Ltd. Analysis shows that the mine water is abundant in dissolved oxygen and has high TDS and high turbidity so the mine water does not need aeration. The effect of removal of iron and manganese by coagulation-sedimentation and the influence of filter material and influent water flow rate on effluent quality were investigated. It is shown that the removal rate of iron can reach 90% while removal of manganese can only reach about 20%. The concentration of iron and manganese in the effluent is lower than 0.1 mg/L with filter material of manganese sand which was immersed in KMnO{sub 4} solution at a filtration rate of 7 - 9 m/h. The results show that the layer of activated compound substance membrane formed on the surface of the manganese sand plays an important role in the removal of manganese. 7 refs., 2 figs., 3 tabs.

  9. Preparation of ultra-light magnetic nanocomposites using highly concentrated emulsions

    International Nuclear Information System (INIS)

    Ghosh, Goutam; Vilchez, Alejandro; Esquena, Jordi; Solans, Conxita; Rodriguez-Abreu, Carlos

    2011-01-01

    Highlights: → Polystyrene-divinylbenzene-iron oxide nanocomposites. → Porous magnetic nanocomposites from highly concentrated emulsions. → Ultralight materials with relatively high magnetic moment. - Abstract: Hybrid inorganic-organic ultra-light magnetic solid foams with iron oxide nanoparticles embedded in a divinylbenzene-polystyrene matrix were prepared using a highly concentrated emulsion polymerization method. Iron oxide nanoparticles with diameters of 3 and 10 nm were synthesized using two different methods. For comparison purposes, nanocomposites with magnetite nanoparticles dispersed in a non-porous polymeric matrix obtained by bulk polymerization were also investigated. Materials were characterized using several techniques such as dynamic light scattering (DLS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), small angle X-ray scattering (SAXS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and magnetization measurements. SEM and TEM images showed that solid foams are made of well-defined macro pores with nanoparticles embedded in the walls. The density of the solid foams was ca. 50-70 kg m -3 , which is about 20 times lighter than the non-porous monoliths. The magnetic measurements show that both nanocomposites are superparamagnetic, and that there are differences regarding the interparticle interactions depending on matrix porosity. The synthesized materials may find applications in adsorbents, tissue reparation, enzyme supports, microreactors, or in water decontamination.

  10. Preparation of ultra-light magnetic nanocomposites using highly concentrated emulsions

    Energy Technology Data Exchange (ETDEWEB)

    Ghosh, Goutam; Vilchez, Alejandro; Esquena, Jordi; Solans, Conxita [Instituto de Quimica Avanzada de Cataluna, Consejo Superior de Investigaciones Cientificas (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Rodriguez-Abreu, Carlos, E-mail: carlos.rodriguez@inl.int [Instituto de Quimica Avanzada de Cataluna, Consejo Superior de Investigaciones Cientificas (IQAC-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); International Iberian Nanotechnology Laboratory (INL), Av. Mestre Jose Veiga, 4715-330 Braga (Portugal)

    2011-10-17

    Highlights: {yields} Polystyrene-divinylbenzene-iron oxide nanocomposites. {yields} Porous magnetic nanocomposites from highly concentrated emulsions. {yields} Ultralight materials with relatively high magnetic moment. - Abstract: Hybrid inorganic-organic ultra-light magnetic solid foams with iron oxide nanoparticles embedded in a divinylbenzene-polystyrene matrix were prepared using a highly concentrated emulsion polymerization method. Iron oxide nanoparticles with diameters of 3 and 10 nm were synthesized using two different methods. For comparison purposes, nanocomposites with magnetite nanoparticles dispersed in a non-porous polymeric matrix obtained by bulk polymerization were also investigated. Materials were characterized using several techniques such as dynamic light scattering (DLS), X-ray diffraction (XRD), thermogravimetric analysis (TGA), small angle X-ray scattering (SAXS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and magnetization measurements. SEM and TEM images showed that solid foams are made of well-defined macro pores with nanoparticles embedded in the walls. The density of the solid foams was ca. 50-70 kg m{sup -3}, which is about 20 times lighter than the non-porous monoliths. The magnetic measurements show that both nanocomposites are superparamagnetic, and that there are differences regarding the interparticle interactions depending on matrix porosity. The synthesized materials may find applications in adsorbents, tissue reparation, enzyme supports, microreactors, or in water decontamination.

  11. Regional and local meteorology influences high-resolution tropospheric ozone concentration in the Los Angeles Basin

    Science.gov (United States)

    Koutzoukis, S.; Jenerette, D.; Chandler, M.; Wang, J.; Ge, C.; Ripplinger, J.

    2017-12-01

    Urban air quality and climate directly affect resident health. The Los Angeles (LA) Basin is a highly populated metropolitan area, with widespread point sources of ozone (O3) precursors (NOx , Volatile Organic Compounds, CO) from fossil fuel combustion. The LA basin exists on a coast-to-mountain gradient, with increasing temperatures towards the Transverse Ranges, which rise to 1700m. Frequently not compliant with 8-hour O3 standards, the LA and South Coast Air Basins are designated as severe and extreme non-attainment areas. Summer weather in the LA basin is characterized by a persistent high pressure system, creating an inversion that traps air pollutants, including O3 precursors, coupled with physical geography that blocks prevailing upper atmosphere air flow. These interactions make neighborhood-level O3 levels more variable than common regional models. Over the summer of 2017, we investigated the importance of local meteorology, wind patterns and air temperature, in transporting and mixing ozone precursors from point sources along the coast-to-mountain gradient. We deployed a network of six EPA federal equivalent method ozone and meteorological sensors in three campaigns in the LA basin along the coast-to-mountain transect. Each campaign, we collaborated with citizen scientists to deploy three sensor stations in two, 4 km2 quadrats, for a total of six high-resolution 4 km2 pixels. O3 concentrations vary greatly along the transect. At the coastal sites, daily O3 ranges from 0ppm to 60ppm and the range increases at the inland sites, to 100ppm. At all sites, there was a positive relationship between wind speed, air temperature, and O3 concentration, with increasing correlation inland. The Pearson correlation coefficient between wind speed and O3 concentration doubles from the coast to inland, and triples between air temperature and O3. The site-specific relationships between O3 and wind direction and temperature vary, suggesting neighborhood-effects from local

  12. 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.

  13. Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations.

    Science.gov (United States)

    Lopez, Sergio; Bermudez, Beatriz; Ortega, Almudena; Varela, Lourdes M; Pacheco, Yolanda M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G

    2011-03-01

    The nature of dietary fats and fasting concentrations of triglycerides affect postprandial hypertriglyceridemia and glucose homeostasis. The objectives were to examine the effects of meals enriched in monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) on postprandial lipid, glucose, and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations. Fourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals (≈10 kcal/kg body weight) containing MUFAs, SFAs, or no fat. Blood samples were collected at baseline and hourly over 8 h for analysis. The high-fat meals significantly increased postprandial concentrations of triglycerides, nonesterified fatty acids, and insulin and postprandial indexes of β cell function. However, postprandial indexes of insulin sensitivity decreased significantly. These effects were significantly attenuated with MUFAs relative to SFAs. MUFAs postprandially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations. These data suggest that, in contrast with SFAs, MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges.

  14. Effect of concentrate feeder design on performance, eating and animal behavior, welfare, ruminal health, and carcass quality in Holstein bulls fed high-concentrate diets.

    Science.gov (United States)

    Verdú, M; Bach, A; Devant, M

    2015-06-01

    A total of 240 Holstein bulls (121 ± 2.0 kg initial BW; 99 ± 1.0 d of age), from 2 consecutive fattening cycles, were randomly allocated in 1 of 6 pens and assigned to 1 of the 3 treatments consisting of different concentrate feeder designs: a control feeder with 4 feeding spaces (CF), a feeder with less concentrate capacity (CFL), and a single-space feeder with lateral protections (SF). Each pen had a straw feeder and a drinker. All animals were fed a high-concentrate diet for ad libitum intake. Concentrate consumption was recorded daily using a computerized feeder, straw consumption was recorded weekly, and BW was recorded every 14 d. Animal behavior was registered on d 1, 3, 5, 8, and 14 and every 28 d by scan sampling. Eating behavior at concentrate feeders was filmed on d 12, 125, and 206. On d 7, 120, and 204, samples of rumen contents were collected for measurement of pH and VFA and blood samples were obtained to analyze NEFA, haptoglobin, glucose, and insulin. Animals were slaughtered after 223 d, and HCW and lesions of the rumen wall and liver were recorded. The accumulative concentrate consumption per animal tended (P = 0.09) to be greater with CF than with CFL and SF. Also, CV of concentrate consumption was greater (P carcass data. Also, no differences among treatments in rumen wall evaluation and liver abscesses were observed. At 7 and 204 d of study, SF bulls had greater (P animal welfare in Holstein bulls fed high-concentrate diets. However, at the beginning, there was evidence that animals fed using SF had problems with adaptation.

  15. Study on automatic control of high uranium concentration solvent extraction with pulse sieve-plate column

    International Nuclear Information System (INIS)

    You Wenzhi; Xing Guangxuan; Long Maoxiong; Zhang Jianmin; Zhou Qin; Chen Fuping; Ye Lingfeng

    1998-01-01

    The author mainly described the working condition of the automatic control system of high uranium concentration solvent extraction with pulse sieve-plate column on a large scale test. The use of the automatic instrument and meter, automatic control circuit, and the best feedback control point of the solvent extraction processing with pulse sieve-plate column are discussed in detail. The writers point out the success of this experiment on automation, also present some questions that should be cared for the automatic control, instruments and meters in production in the future

  16. Carbon assimilation in Eucalyptus urophylla grown under high atmospheric CO2 concentrations: A proteomics perspective.

    Science.gov (United States)

    Santos, Bruna Marques Dos; Balbuena, Tiago Santana

    2017-01-06

    Photosynthetic organisms may be drastically affected by the future climate projections of a considerable increase in CO 2 concentrations. Growth under a high concentration of CO 2 could stimulate carbon assimilation-especially in C3-type plants. We used a proteomics approach to test the hypothesis of an increase in the abundance of the enzymes involved in carbon assimilation in Eucalyptus urophylla plants grown under conditions of high atmospheric CO 2 . Our strategy allowed the profiling of all Calvin-Benson cycle enzymes and associated protein species. Among the 816 isolated proteins, those involved in carbon fixation were found to be the most abundant ones. An increase in the abundance of six key enzymes out of the eleven core enzymes involved in carbon fixation was detected in plants grown at a high CO 2 concentration. Proteome changes were corroborated by the detection of a decrease in the stomatal aperture and in the vascular bundle area in Eucalyptus urophylla plantlets grown in an environment of high atmospheric CO 2 . Our proteomics approach indicates a positive metabolic response regarding carbon fixation in a CO 2 -enriched atmosphere. The slight but significant increase in the abundance of the Calvin enzymes suggests that stomatal closure did not prevent an increase in the carbon assimilation rates. The sample enrichment strategy and data analysis used here enabled the identification of all enzymes and most protein isoforms involved in the Calvin-Benson-Bessham cycle in Eucalyptus urophylla. Upon growth in CO 2 -enriched chambers, Eucalyptus urophylla plantlets responded by reducing the vascular bundle area and stomatal aperture size and by increasing the abundance of six of the eleven core enzymes involved in carbon fixation. Our proteome approach provides an estimate on how a commercially important C3-type plant would respond to an increase in CO 2 concentrations. Additionally, confirmation at the protein level of the predicted genes involved in

  17. Nonlinear mixed effects dose response modeling in high throughput drug screens: application to melanoma cell line analysis.

    Science.gov (United States)

    Ding, Kuan-Fu; Petricoin, Emanuel F; Finlay, Darren; Yin, Hongwei; Hendricks, William P D; Sereduk, Chris; Kiefer, Jeffrey; Sekulic, Aleksandar; LoRusso, Patricia M; Vuori, Kristiina; Trent, Jeffrey M; Schork, Nicholas J

    2018-01-12

    Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC 50 ). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations. We consider the application of two methods, each rooted in nonlinear mixed effects (NLME) models, that test the relationship relationships between estimated cell line DRCs and factors that might mitigate response. Both methods leverage estimation and testing techniques that consider the simultaneous analysis of different cell lines to draw inferences about any one cell line. One of the methods is designed to provide an omnibus test of the differences between cell line DRCs that is not focused on any one aspect of the DRC (such as the IC 50 value). We simulated different settings and compared the different methods on the simulated data. We also compared the proposed methods against traditional IC 50 -based methods using 40 melanoma cell lines whose transcriptomes, proteomes, and, importantly, BRAF and related mutation profiles were available. Ultimately, we find that the NLME-based methods are more robust, powerful and, for the omnibus test, more flexible, than traditional methods. Their application to the melanoma cell lines reveals insights into factors that may be clinically useful.

  18. Composition of highly concentrated silicate electrolytes and ultrasound influencing the plasma electrolytic oxidation of magnesium

    Science.gov (United States)

    Simchen, F.; Rymer, L.-M.; Sieber, M.; Lampke, T.

    2017-03-01

    Magnesium and its alloys are increasingly in use as lightweight construction materials. However, their inappropriate corrosion and wear resistance often prevent their direct practical use. The plasma electrolytic oxidation (PEO) is a promising, environmentally friendly method to improve the surface characteristics of magnesium materials by the formation of oxide coatings. These PEO layers contain components of the applied electrolyte and can be shifted in their composition by increasing the concentration of the electrolyte constituents. Therefore, in contrast to the use of conventional low concentrated electrolytes, the process results in more stable protective coatings, in which electrolyte species are the dominating constitutes. In the present work, the influence of the composition of highly concentrated alkaline silicate electrolytes with additives of phosphate and glycerol on the quality of PEO layers on the magnesium alloy AZ31 was examined. The effect of ultrasound coupled into the electrolyte bath was also considered. The process was monitored by recording the electrical process variables with a transient recorder and by observation of the discharge phenomena on the sample surface with a camera. The study was conducted on the basis of a design of experiments. The effects of the process parameter variation are considered with regard to the coatings thickness, hardness and corrosion resistance. Information about the statistical significance of the effects of the parameters on the considered properties is obtained by an analysis of variance (ANOVA).

  19. High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

    International Nuclear Information System (INIS)

    Landim, M.B.P.; Dourado, P.M.M.; Casella-Filho, A.; Chagas, A.C.P.; Luz, P.L. da

    2013-01-01

    A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats

  20. High plasma concentrations of asymmetric dimethylarginine inhibit ischemic cardioprotection in hypercholesterolemic rats

    Energy Technology Data Exchange (ETDEWEB)

    Landim, M.B.P.; Dourado, P.M.M.; Casella-Filho, A.; Chagas, A.C.P.; Luz, P.L. da [Unidade de Aterosclerose, Instituto do Coração, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2013-05-10

    A low concentration of nitric oxide associated with a high concentration of asymmetric dimethylarginine (ADMA) can explain the lack of ischemic cardioprotection observed in the presence of hypercholesterolemia. The objective of the present study was to evaluate the effect of hypercholesterolemia on ischemic pre- and postconditioning and its correlation with plasma concentrations of ADMA. Male Wistar rats (6-8 weeks old) fed a 2% cholesterol diet (n = 21) for 8 weeks were compared to controls (n = 25) and were subjected to experimental myocardial infarction and reperfusion, with ischemic pre- and postconditioning. Total cholesterol and ADMA were measured in plasma before the experimental infarct and the infarct area was quantified. Weight, total cholesterol and plasma ADMA (means ± SE; 1.20 ± 0.06, 1.27 ± 0.08 and 1.20 ± 0.08 vs 0.97 ± 0.04, 0.93 ± 0.05 and 0.97 ± 0.04 µM) were higher in animals on the hypercholesterolemic diet than in controls, respectively. Cardioprotection did not reduce infarct size in the hypercholesterolemic animals (pre: 13.55% and post: 8% compared to 7.95% observed in the group subjected only to ischemia and reperfusion), whereas infarct size was reduced in the animals on a normocholesterolemic diet (pre: 8.25% and post: 6.10% compared to 12.31%). Hypercholesterolemia elevated ADMA and eliminated the cardioprotective effects of ischemic pre- and postconditioning in rats.

  1. Compact high-sensitivity potentiometer for detection of low ion concentrations in liquids

    Science.gov (United States)

    Balevicius, Z.; Lescinskas, R.; Celiesiute, R.; Stirke, A.; Balevicius, S.; Kersulis, S.; Bleizgys, V.; Maciuleviciene, R.; Ramanavicius, A.; Zurauskiene, N.

    2018-04-01

    The compact potentiometer, based on an electronic circuit protected from electrostatic and electromagnetic interference, was developed for the measurement of low ion concentrations in liquids. The electronic circuit of the potentiometer, consisting of analogous and digital parts, enables the measurement of fA currents. This makes it possible to perform reliable measurements of ion concentrations in liquids that are as small as 10-8-10-7M. The instrument was tested using electrodes that were selective for tetraphenylphosphonium (TPP+) ions. It was demonstrated that the characteristic response time of the potentiometer electronic circuit to changes in the concentration of these ions in a liquid was in the order of 10 s. An investigation of TPP+ absorption by baker yeast has shown that this device can be successfully used for long term (several hours) measurements with zero signal drift, which was about 1 μV/s. Finally, due to the small dimensions of the electronic circuit (7.5 × 2 × 1.5 cm), this potentiometer can be easily installed at a large apparatus in the laboratory condition (≈25 °C), such as high pulsed electrical generators of magnetic fields that are used in electroporation studies of biological cells.

  2. Effect of thymol and carvacrol on nutrient digestibility in rams fed high or low concentrate diets.

    Science.gov (United States)

    Zamiri, M J; Azizabadi, E; Momeni, Z; Rezvani, M R; Atashi, H; Akhlaghi, A

    2015-01-01

    Published data on the effects of essential oils (EO) on in vivo nutrient digestibility in sheep are contradictory. In 2 experiments, the effect of thymol and carvacrol on nutrient digestibility was studied in sheep fed with high (70%) or low (52%) concentrate diets, using incomplete Latin Square designs. The essential oils were mixed with the concentrate portion of the diet at the rate of 0.0, 0.3, or 0.6 g per kg dry matter (DM) diet. Supplementation of thymol had no significant effect on digestibility of dry matter (DM), organic matter (OM), crude protein (CP) and acid detergent fiber (ADF). The main effect of thymol on neutral detergent fiber (NDF) and ether extract (EE) digestibility and on nitrogen balance (NB) was significant (Pdigestibility. The main effect of carvacrol on ruminal ammonia levels and NB was significant, but within each level of dietary concentrate no significant differences were observed in ammonia levels and NB. Inclusion of 0.3 g/kg diet DM of carvacrol or thyme was more effective than 0.6 g/kg diet DM in terms of NB but neither dose affected nutrient digestibility. Future research should determine the long-term effects of essential oils on digestibility and performance in sheep, before recommendation can be made for their use under practical husbandry conditions.

  3. High resolution 4-D spectroscopy with sparse concentric shell sampling and FFT-CLEAN.

    Science.gov (United States)

    Coggins, Brian E; Zhou, Pei

    2008-12-01

    Recent efforts to reduce the measurement time for multidimensional NMR experiments have fostered the development of a variety of new procedures for sampling and data processing. We recently described concentric ring sampling for 3-D NMR experiments, which is superior to radial sampling as input for processing by a multidimensional discrete Fourier transform. Here, we report the extension of this approach to 4-D spectroscopy as Randomized Concentric Shell Sampling (RCSS), where sampling points for the indirect dimensions are positioned on concentric shells, and where random rotations in the angular space are used to avoid coherent artifacts. With simulations, we show that RCSS produces a very low level of artifacts, even with a very limited number of sampling points. The RCSS sampling patterns can be adapted to fine rectangular grids to permit use of the Fast Fourier Transform in data processing, without an apparent increase in the artifact level. These artifacts can be further reduced to the noise level using the iterative CLEAN algorithm developed in radioastronomy. We demonstrate these methods on the high resolution 4-D HCCH-TOCSY spectrum of protein G's B1 domain, using only 1.2% of the sampling that would be needed conventionally for this resolution. The use of a multidimensional FFT instead of the slow DFT for initial data processing and for subsequent CLEAN significantly reduces the calculation time, yielding an artifact level that is on par with the level of the true spectral noise.

  4. Application of Hill's equation for estimating area under the concentration-time curve (AUC) and use of time to AUC 90% for expressing kinetics of drug disposition.

    Science.gov (United States)

    Cheng, Hsien C

    2009-01-01

    Half life and its derived pharmacokinetic parameters are calculated on an assumption that the terminal phase of drug disposition follows a constant rate of disposition. In reality, this assumption may not necessarily be the case. A new method is needed for analyzing PK parameters if the disposition does not follow a first order PK kinetic. Cumulative area under the concentration-time curve (AUC) is plotted against time to yield a hyperbolic (or sigmoidal) AUC-time relationship curve which is then analyzed by Hill's equation to yield AUC(inf), time to achieving AUC50% (T(AUC50%)) or AUC90% (T(AUC90%)), and the Hill's slope. From these parameters, an AUC-time relationship curve can be reconstructed. Projected plasma concentration can be calculated for any time point. Time at which cumulative AUC reaches 90% (T(AUC90%)) can be used as an indicator for expressing how fast a drug is cleared. Clearance is calculated in a traditional manner (i.v. dose/AUC(inf)), and the volume of distribution is proposed to be calculated at T(AUC50%) (0.5 i.v. dose/plasma concentration at T(AUC50%)). This method of estimating AUC is applicable for both i.v. and oral data. It is concluded that the Hill's equation can be used as an alternative method for estimating AUC and analysis of PK parameters if the disposition does not follow a first order kinetic. T(AUC90%) is proposed to be used as an indicator for expressing how fast a drug is cleared from the system.

  5. Unexpectedly high ultrafine aerosol concentrations above East Antarctic sea-ice

    Science.gov (United States)

    Humphries, R. S.; Klekociuk, A. R.; Schofield, R.; Keywood, M.; Ward, J.; Wilson, S. R.

    2015-10-01

    The effect of aerosols on clouds and their radiative properties is one of the largest uncertainties in our understanding of radiative forcing. A recent study has concluded that better characterisation of pristine, natural aerosol processes leads to the largest reduction in these uncertainties. Antarctica, being far from anthropogenic activities, is an ideal location for the study of natural aerosol processes. Aerosol measurements in Antarctica are often limited to boundary layer air-masses at spatially sparse coastal and continental research stations, with only a handful of studies in the sea ice region. In this paper, the first observational study of sub-micron aerosols in the East Antarctic sea ice region is presented. Measurements were conducted aboard the ice-breaker Aurora Australis in spring 2012 and found that boundary layer condensation nuclei (CN3) concentrations exhibited a five-fold increase moving across the Polar Front, with mean Polar Cell concentrations of 1130 cm-3 - higher than any observed elsewhere in the Antarctic and Southern Ocean region. The absence of evidence for aerosol growth suggested that nucleation was unlikely to be local. Air parcel trajectories indicated significant influence from the free troposphere above the Antarctic continent, implicating this as the likely nucleation region for surface aerosol, a similar conclusion to previous Antarctic aerosol studies. The highest aerosol concentrations were found to correlate with low pressure systems, suggesting that the passage of cyclones provided an accelerated pathway, delivering air-masses quickly from the free-troposphere to the surface. After descent from the Antarctic free troposphere, trajectories suggest that sea ice boundary layer air-masses travelled equator-ward into the low albedo Southern Ocean region, transporting with them emissions and these aerosol nuclei where, after growth, may potentially impact on the region's radiative balance. The high aerosol concentrations and

  6. Individual and environmental risk factors for high blood lead concentrations in Danish indoor shooters.

    Science.gov (United States)

    Grandahl, Kasper; Suadicani, Poul; Jacobsen, Peter

    2012-08-01

    International studies have shown blood lead at levels causing health concern in recreational indoor shooters. We hypothesized that Danish recreational indoor shooters would also have a high level of blood lead, and that this could be explained by shooting characteristics and the physical environment at the shooting range. This was an environmental case study of 58 male and female shooters from two indoor shooting ranges with assumed different ventilation and cleaning conditions. Information was obtained on general conditions including age, gender, tobacco and alcohol use, and shooting conditions: weapon type, number of shots fired, frequency of stays at the shooting range and hygiene habits. A venous blood sample was drawn to determine blood lead concentrations; 14 non-shooters were included as controls. Almost 60% of the shooters, hereof five out of 14 women, had a blood lead concentration above 0.48 micromol/l, a level causing long-term health concern. All controls had blood lead values below 0.17 micromol/l. Independent significant associations with blood lead concentrations above 0.48 micromol/l were found for shooting at a poorly ventilated range, use of heavy calibre weapons, number of shots and frequency of stays at the shooting range. A large proportion of Danish recreational indoor shooters had potentially harmful blood lead concentrations. Ventilation, amounts of shooting, use of heavy calibre weapons and stays at the shooting ranges were independently associated with increased blood lead. The technical check at the two ranges was performed by the Danish Technological Institute and costs were defrayed by the Danish Rifle Association. To pay for the analyses of blood lead, the study was supported by the The Else & Mogens Wedell-Wedellsborg Foundation. The Danish Regional Capital Scientific Ethics Committee approved the study, protocol number H-4-2010-130.

  7. Effect of pH and comedication on gastrointestinal absorption of posaconazole: monitoring of intraluminal and plasma drug concentrations.

    Science.gov (United States)

    Walravens, Jeroen; Brouwers, Joachim; Spriet, Isabel; Tack, Jan; Annaert, Pieter; Augustijns, Patrick

    2011-11-01

    Posaconazole (Noxafil®) is an extended-spectrum triazole antifungal agent for prevention and treatment of invasive fungal infections. An inadequate dietary intake and abnormal gastric pH levels are common in critically ill patients receiving antifungal treatment with posaconazole, resulting in unpredictable bioavailability and sub-therapeutic plasma concentrations. This study was carried out to elucidate the impact of pH on posaconazole absorption and to explore the underlying mechanisms of enhanced intestinal absorption when coadministering an acidic carbonated beverage. In contrast to previously published studies, in which only plasma concentrations were determined, we also explored the gastric and intestinal behaviour of posaconazole after a single oral dose. A crossover study was performed in five healthy subjects. A single dose (10 mL) of posaconazole suspension (40 mg/mL) was administered orally in four different conditions: with 330 mL of water (condition 1); with 330 mL of a cola beverage [Coca-Cola®] (condition 2); with 330 mL of water following intake of the proton pump inhibitor esomeprazole 40 mg once daily for 3 days (condition 3); or with 330 mL of Coca-Cola® following intake of esomeprazole 40 mg once daily for 3 days (condition 4). After administration, gastrointestinal fluid and plasma samples were collected at regular time points, and posaconazole concentrations were determined. Compared with administration with water, coadministration of Coca-Cola® did not alter the pH of the intraluminal environment but did significantly increase posaconazole gastric concentrations (+102%; p Coca-Cola® and prolonged gastric residence. Coadministration of esomeprazole led to an increased gastric pH, which was accompanied by decreased posaconazole absorption; the mean plasma and gastric area under the concentration-time curve (AUC) values decreased by 37% and 84%, respectively. Simultaneous intake of Coca-Cola® could not completely compensate for the

  8. 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...

  9. 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.

  10. 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.

  11. 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.

  12. Extremely high hole concentrations in c-plane GaN

    Energy Technology Data Exchange (ETDEWEB)

    Trybus, Elaissa; Moseley, Michael; Henderson, Walter; Billingsley, Daniel [Department of Electrical and Computer Engineering, Georgia Institute of Technology, Atlanta, GA (United States); Namkoong, Gon [Old Dominion University, Applied Research Center, Newport News, VA (United States); Look, David C. [Wright State University, Semiconductor Research Center, Dayton, OH (United States); Doolittle, W.A.

    2009-06-15

    Metal Modulated Epitaxy (S. D. Burnham et al., J. Appl. Phys. 104, 024902 (2008)[1]) is extended to include modulation of both the shutters of Ga and Mg, the Mg being delivered from a Veeco corrosive series valved cracker (S. D. Burnham et al., Mater. Res. Soc. Proc. 798, Y8.11 (2003)[2]). The Ga fluxes used are sufficiently large that droplets rapidly form when the Ga shutter opens and are subsequently depleted when the Ga shutter closes. The result is the ability to limit surface faceting while predominantly growing under average N-rich growth conditions and thus, possibly reduce N-vacancy defects. N-vacancy defects are known to result in compensation. This ability to grow higher quality materials under N-rich conditions results in very high hole concentrations and low resistivity p-type materials. Hole concentrations as high as 2 x 10{sup 19} cm{sup -3} have been achieved on c-plane GaN resulting in resistivities as low as 0.38 ohm-cm. The dependence on Ga flux, shutter timing, the corresponding RHEED images for each condition is detailed and clearly show minimization of faceting and crystal quality variations as determined by X-ray diffraction. Quantification of the Mg incorporation and residual impurities such as hydrogen, oxygen, and carbon by SIMS, eliminates co-doping, while temperature dependent hall measurements show reduced activation energies. X-ray diffraction data compares crystalline quality with hole concentration. (copyright 2009 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

  13. Adaptation to high salt concentrations in halotolerant/ halophilic fungi: a molecular perspective

    Directory of Open Access Journals (Sweden)

    Ana ePlemenitas

    2014-05-01

    Full Text Available Molecular studies of salt tolerance of eukaryotic microorganisms have until recently been limited to the baker’s yeast Saccharomyces cerevisiae and a few other moderately halotolerant yeast. Discovery of the extremely halotolerant and adaptable fungus Hortaea werneckii and the obligate halophile Wallemia ichthyophaga introduced two new model organisms into studies on the mechanisms of salt tolerance in eukaryotes. H. werneckii is unique in its adaptability to fluctuations in salt concentrations, as it can grow without NaCl as well as in the presence of up to 5 M NaCl. On the other hand, W. ichthyophaga requires at least 1.5 M NaCl for growth, but also grows in up to 5 M NaCl. Our studies have revealed the novel and intricate molecular mechanisms used by these fungi to combat high salt concentrations, which differ in many aspects between the extremely halotolerant H. werneckii and the halophilic W. ichthyophaga. Specifically, the high osmolarity glycerol signalling pathway that is important for sensing and responding to increased salt concentrations is here compared between H. werneckii and W. ichthyophaga. In both of these fungi, the key signalling components are conserved, but there are structural and regulation differences between these pathways in H. werneckii and W. ichthyophaga. We also address differences that have been revealed from analysis of their newly sequenced genomes. The most striking characteristics associated with H. werneckii are the large genetic redundancy, the expansion of genes encoding metal cation transporters, and a relatively recent whole genome duplication. In contrast, the genome of W. ichthyophaga is very compact, as only 4,884 protein-coding genes are predicted, which cover almost three quarters of the sequence. Importantly, there has been a significant increase in their hydrophobins, cell-wall proteins that have multiple cellular functions.

  14. Plasmonic Refractive Index Sensor with High Figure of Merit Based on Concentric-Rings Resonator

    Science.gov (United States)

    Zhang, Zhaojian; Yang, Junbo; He, Xin; Zhang, Jingjing; Huang, Jie; Chen, Dingbo; Han, Yunxin

    2018-01-01

    A plasmonic refractive index (RI) sensor based on metal-insulator-metal (MIM) waveguide coupled with concentric double rings resonator (CDRR) is proposed and investigated numerically. Utilizing the novel supermodes of the CDRR, the FWHM of the resonant wavelength can be modulated, and a sensitivity of 1060 nm/RIU with high figure of merit (FOM) 203.8 is realized in the near-infrared region. The unordinary modes, as well as the influence of structure parameters on the sensing performance, are also discussed. Such plasmonic sensor with simple framework and high optical resolution could be applied to on-chip sensing systems and integrated optical circuits. Besides, the special cases of bio-sensing and triple rings are also discussed. PMID:29300331

  15. Derived air concentration for high exposure plutonium : revised values based on ICRP -30 recommendations

    International Nuclear Information System (INIS)

    Sharma, Lata; Janardhanan, S.; Krishnamurthi, T.N.

    1983-01-01

    Derived Air Concentration (DAC) limits for plutonium isotopic mixtures, as obtained from reprocessing of spent fuel heavy water reactors, are presented in this paper. DAC for the mixtures is expressed in terms of alpha activity of plutonium. Growth of 241 Am in the product is taken into consideration. Current recommedations on DAC limits for individual Pu isotopes, as laid down in ICRP-30 report, are used for estimating DAC for the mixture. DACsub(α) for high exposure plutonium is found to be less by a factor of 2-3, when compared with the limit for 239 Pu. As a result, detection and alarm limits for air monitoring instruments should be scaled down while handling high exposure plutonium. (author)

  16. Derived air concentration for high exposure plutonium : revised values based on ICRP -30 recommendations

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, L.; Janardhanan, S.; Krishnamurthi, T.N. (Bhabha Atomic Research Centre, Bombay (India). Health Physics Div.)

    Derived Air Concentration (DAC) limits for plutonium isotopic mixtures, as obtained from reprocessing of spent fuel heavy water reactors, are presented in this paper. DAC for the mixtures is expressed in terms of alpha activity of plutonium. Growth of /sup 241/Am in the product is taken into consideration. Current recommedations on DAC limits for individual Pu isotopes, as laid down in ICRP-30 report, are used for estimating DAC for the mixture. DACsub(..cap alpha..) for high exposure plutonium is found to be less by a factor of 2-3, when compared with the limit for /sup 239/Pu. As a result, detection and alarm limits for air monitoring instruments should be scaled down while handling high exposure plutonium.

  17. 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

  18. 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