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Sample records for residual drug concentration

  1. Concentrations of veterinary drug residues in milk from individual farms in Croatia

    Directory of Open Access Journals (Sweden)

    Nina Bilandžić

    2011-09-01

    Full Text Available A total of 119 raw milk samples collected at individual small milk-producing facilities and collection tanks of milk routes from five counties of east and north continental Croatia were examined for chloramphenicol, sulfonamides, tetracyclines, gentamicin, streptomycin, dihydrostreptomycin, flumequine and enrofloxacin from January to March of 2011. Immunoassay methods used for drug determination were validated according to the guidelines laid down by European Commission Decision 2002/657/EC. Data indicated that the methods are appropriate for the detection of antibiotics measured. Measured mean values (μg L-1 of antibiotics were: 0.005 for chloramphenicol, 3.67 for sulfonamides, 2.83 for tetracyclines, 1.10 for gentamicin, 2.64 for streptomycin, 7.67 for dihydrostreptomycin, 10.4 for flumequine and 4.11 for enrofloxacin. None of samples analyzed showed the presence of veterinary drug residues above the maximum residues levels (MRLs established by European Union and Croatian legislation. The calculated estimated daily intakes (EDIs for the average daily milk consumption of 300 mL for an adult in Croatia for examined antibiotics showed levels 20 to 1640 times lower than the values of acceptable daily intakes (ADIs fixed by European Medicines Agency and World Health Organization. This suggested that toxicological risk associated with the consumption of analysed milk could not be considered a public health issue with regards to these veterinary drugs.

  2. Artificial Neural Networks and Concentration Residual Augmented ...

    African Journals Online (AJOL)

    Artificial Neural Networks and Concentration Residual Augmented Classical Least Squares for the Simultaneous Determination of Diphenhydramine, Benzonatate, Guaifenesin and Phenylephrine in their Quaternary Mixture.

  3. Residual methamphetamine in decontaminated clandestine drug laboratories.

    Science.gov (United States)

    Patrick, Glen; Daniell, William; Treser, Charles

    2009-03-01

    This pilot cross-sectional study examined three previously decontaminated residential clandestine drug laboratories (CDLs) in Washington State to determine the distribution and magnitude of residual methamphetamine concentrations relative to the state decontamination standard. A total of 159 discrete random methamphetamine wipe samples were collected from the three CDLs, focusing on the master bedroom, bathroom, living room, and kitchen at each site. Additional samples were collected from specific non-random locations likely to be contacted by future residents (e.g., door knobs and light switches). Samples were analyzed for methamphetamine by EPA method 8270 for semivolatile organic chemicals. Overall, 59% of random samples and 75% of contact point samples contained methamphetamine in excess of the state decontamination standard (0.1 micro g/100 cm(2)). At each site, methamphetamine concentrations were generally higher and more variable in rooms where methamphetamine was prepared and used. Even compared with the less stringent standard adopted in Colorado (0.5 micro g/100cm(2)), a substantial number of samples at each site still demonstrated excessive residual methamphetamine (random samples, 25%; contact samples, 44%). Independent oversight of CDL decontamination in residential structures is warranted to protect public health. Further research on the efficacy of CDL decontamination procedures and subsequent verification of methods is needed.

  4. Artificial Neural Networks and Concentration Residual Augmented ...

    African Journals Online (AJOL)

    Methoxyphenoxy) - 1, 2 - propanediol] is an alpha - adrenergic sympathomimetic agent which stimulates alpha - adrenergic receptors, producing pronounced vasoconstriction [3]. The combination of the four drugs is used for treating bronchial spasm and as antitussive. The UV absorption spectra of the four drugs display.

  5. Pharmacokinetics, efficacy prediction indexes and residue depletion of antibacterial drugs.

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    Arturo Anadón

    2016-06-01

    Full Text Available Pharmacokinetics behaviour of the antibacterial in food producing animals, provides information on the rates of absorption and elimination, half-life in plasma and tissue, elimination pathways and metabolism. The dose and the dosing interval of the antimicrobial can be justified by considering the pharmacokinetic/pharmacodynamic (PK/PD relationship, if established, as well as the severity of the disease, whereas the number of administrations should be in line with the nature of the disease. The target population for therapy should be well defined and possible to identify under field conditions. Based on in vitro susceptibility data, and target animal PK data, an analysis for the PK/PD relationship may be used to support dose regimen selection and interpretation criteria for a clinical breakpoint. Therefore, for all antibacterials with systemic activity, the MIC data collected should be compared with the concentration of the compound at the relevant biophase following administration at the assumed therapeutic dose as recorded in the pharmacokinetic studies. Currently, the most frequently used parameters to express the PK/PD relationship are Cmax/MIC (maximum serum concentration/MIC, %T > MIC (fraction of time in which concentration exceeds MIC and AUC/MIC (area under the inhibitory concentration– time curve/MIC. Furthermore, the pharmacokinetic parameters provide the first indication of the potential for persistent residues and the tissues in which they may occur. The information on residue depletion in food-producing animals, provides the data on which MRL recommendations will be based. A critical factor in the antibacterial medication of all food-producing animals is the mandatory withdrawal period, defined as the time during which drug must not be administered prior to the slaughter of the animal for consumption. The withdrawal period is an integral part of the regulatory authorities’ approval process and is designed to ensure that no

  6. Milk quality parameters associated with the occurrence of veterinary drug residues in bulk tank milk

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    Lidia Cristina Almeida Picinin

    Full Text Available ABSTRACT Veterinary drug residues in bulk tank milk are important to all sectors of the dairy chain because they are one of the major factors which determine the safety of the final product. This study attempted to identify milk quality parameters that are associated with the occurrence of veterinary drug residues using multivariate principal component analysis (PCA. A total of 132 raw milk samples were collected from 45 dairy farms in the state of Minas Gerais - Brazil and analyzed for 42 analytes, including pyrethroids, macrocyclic lactones and antibacterials, using liquid chromatography coupled with mass spectrometry in tandem mode and gas chromatography with electron capture detection. Out of the 132 milk samples, 40 samples tested positive for at least one analyte (above the detection limit. The milk parameters associated with the antimicrobial residues by confirmatory tests were lactose and nonfat concentrations, as revealed by PCA. This analysis showed that fat and total solid concentrations, as well as the somatic cell and total bacteria counts were associated with macrocyclic lactone residues in bulk tank milk. A PCA assessing pyrethroid residues in bulk tank milk revealed that the lactose and nonfat solid concentrations and titratable acidity were inversely associated with these residues. Thus, the data analysis indicated that the veterinary drug residues were associated with certain milk quality parameters that can be used to target farms at higher risk of veterinary drug residue contamination for testing programs in combination with incentives, education and training programs to improve mammary health, milk hygiene and safety.

  7. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis

    International Nuclear Information System (INIS)

    2016-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  8. 76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Science.gov (United States)

    2011-08-17

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0246] Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA...

  9. Preparation and Properties of Agricultural Residuals-Iron Concentrate Pellets

    OpenAIRE

    Liu, Zhulin; Bi, Xuegong; Gao, Zeping; Wang, Yayu

    2017-01-01

    In this paper, carbon-containing pellets were prepared by using crop-derived charcoal made from agricultural residuals and iron ore concentrates, and their pelletizing performance and properties were studied. Experimental results showed that the strengths of pellets were related to the particle size of concentrates and the content of moisture, bentonite, and crop-derived charcoal fines in the pelletizing mixture and the temperature of roasting and reduction. That the granularity of raw materi...

  10. Assessment of drug usage and antimicrobial residues in milk on ...

    African Journals Online (AJOL)

    Milk samples were also collected for evaluation of antimicrobial drug residues using three tests; the Delvotest® SP, agar well diffusion and agar plate disc assays. On the day of farm visit, 25.4% of study farms had various drugs used to treat animals, categorised as antimicrobials (54.2%), anthelmintics (25.0%), ...

  11. 77 FR 72254 - New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food

    Science.gov (United States)

    2012-12-05

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Parts 500, 520, 522, 524, 529, 556, and 558 [Docket No. FDA-2012-N-1067] RIN 0910-AG17 New Animal Drugs; Updating Tolerances for Residues of New Animal Drugs in Food AGENCY: Food and Drug Administration, HHS. ACTION...

  12. Impacts of feeding preweaned calves milk containing drug residues on the functional profile of the fecal microbiota

    OpenAIRE

    Pereira, Richard Van Vleck; Carroll, Laura M.; Lima, Svetlana; Foditsch, Carla; Siler, Julie D.; Bicalho, Rodrigo Carvalho; Warnick, Lorin D.

    2018-01-01

    Feeding drug residue-containing milk to calves is common worldwide and no information is currently available on the impact on the functional profile of the fecal microbiota. Our objective was to characterize the functional profile of the fecal microbiota of preweaned dairy calves fed raw milk with residual concentrations of antimicrobials commonly found in waste milk from birth to weaning. Calves were assigned to a controlled feeding trial being fed milk with no drug residues or milk with ant...

  13. In vivo selection of resistant E. coli after ingestion of milk with added drug residues.

    Science.gov (United States)

    Pereira, Richard Van Vleck; Siler, Julie D; Bicalho, Rodrigo Carvalho; Warnick, Lorin D

    2014-01-01

    Antimicrobial resistance represents a major global threat to modern medicine. In vitro studies have shown that very low concentrations of drugs, as frequently identified in the environment, and in foods and water for human and animal consumption, can select for resistant bacteria. However, limited information is currently available on the in vivo impact of ingested drug residues. The objective of our study was to evaluate the effect of feeding preweaned calves milk containing antimicrobial drug residues (below the minimum inhibitory concentration), similar to concentrations detected in milk commonly fed to dairy calves, on selection of resistant fecal E. coli in calves from birth to weaning. At birth, thirty calves were randomly assigned to a controlled feeding trial where: 15 calves were fed raw milk with no drug residues (NR), and 15 calves were fed raw milk with drug residues (DR) by adding ceftiofur, penicillin, ampicillin, and oxytetracycline at final concentrations in the milk of 0.1, 0.005, 0.01, and 0.3 µg/ml, respectively. Fecal samples were rectally collected from each calf once a week starting at birth prior to the first feeding in the trial (pre-treatment) until 6 weeks of age. A significantly greater proportion of E. coli resistant to ampicillin, cefoxitin, ceftiofur, streptomycin and tetracycline was observed in DR calves when compared to NR calves. Additionally, isolates from DR calves had a significant decrease in susceptibility to ceftriaxone and ceftiofur when compared to isolates from NR calves. A greater proportion of E. coli isolates from calves in the DR group were resistant to 3 or more antimicrobial drugs when compared to calves in the ND group. These findings highlight the role that low concentrations of antimicrobial drugs have on the evolution and selection of resistance to multiple antimicrobial drugs in vivo.

  14. In vivo selection of resistant E. coli after ingestion of milk with added drug residues.

    Directory of Open Access Journals (Sweden)

    Richard Van Vleck Pereira

    Full Text Available Antimicrobial resistance represents a major global threat to modern medicine. In vitro studies have shown that very low concentrations of drugs, as frequently identified in the environment, and in foods and water for human and animal consumption, can select for resistant bacteria. However, limited information is currently available on the in vivo impact of ingested drug residues. The objective of our study was to evaluate the effect of feeding preweaned calves milk containing antimicrobial drug residues (below the minimum inhibitory concentration, similar to concentrations detected in milk commonly fed to dairy calves, on selection of resistant fecal E. coli in calves from birth to weaning. At birth, thirty calves were randomly assigned to a controlled feeding trial where: 15 calves were fed raw milk with no drug residues (NR, and 15 calves were fed raw milk with drug residues (DR by adding ceftiofur, penicillin, ampicillin, and oxytetracycline at final concentrations in the milk of 0.1, 0.005, 0.01, and 0.3 µg/ml, respectively. Fecal samples were rectally collected from each calf once a week starting at birth prior to the first feeding in the trial (pre-treatment until 6 weeks of age. A significantly greater proportion of E. coli resistant to ampicillin, cefoxitin, ceftiofur, streptomycin and tetracycline was observed in DR calves when compared to NR calves. Additionally, isolates from DR calves had a significant decrease in susceptibility to ceftriaxone and ceftiofur when compared to isolates from NR calves. A greater proportion of E. coli isolates from calves in the DR group were resistant to 3 or more antimicrobial drugs when compared to calves in the ND group. These findings highlight the role that low concentrations of antimicrobial drugs have on the evolution and selection of resistance to multiple antimicrobial drugs in vivo.

  15. Application of Stable Isotope in Detection of Veterinary Drug Residues

    International Nuclear Information System (INIS)

    Wang Wei; Liu Zhanfeng; Du Xiaoning

    2010-01-01

    In recent years, there has happened a series of significant food safety events worldwide, which lower down consumers' confidence in food safety, and they are taking increasing care about the sources of their foods. The safety problem of animal-origin foods has become a global topic for discussion. Therefore, it is a pressing task to establish a precise, sensitive and reliable method for analyzing veterinary drug residue. An introduction of the present status regarding veterinary drug residue analysis was made in the paper, and it briefly summarized the limit of detection (LOD) and quantification (LOQ) which could be reached in veterinary drug residue analysis by isotopic internal standard method domestically and abroad. The paper also made a review of the progress in applied research of stable isotope labeled compound in veterinary drug residue analysis of, such as, antibiotic medicines, furans and sulfonamides. The paper elucidated the great importance of the application of stable isotopes in the sane development of China's food safety system. (authors)

  16. Protein microarray: sensitive and effective immunodetection for drug residues

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    Zer Cindy

    2010-02-01

    Full Text Available Abstract Background Veterinary drugs such as clenbuterol (CL and sulfamethazine (SM2 are low molecular weight ( Results The artificial antigens were spotted on microarray slides. Standard concentrations of the compounds were added to compete with the spotted antigens for binding to the antisera to determine the IC50. Our microarray assay showed the IC50 were 39.6 ng/ml for CL and 48.8 ng/ml for SM2, while the traditional competitive indirect-ELISA (ci-ELISA showed the IC50 were 190.7 ng/ml for CL and 156.7 ng/ml for SM2. We further validated the two methods with CL fortified chicken muscle tissues, and the protein microarray assay showed 90% recovery while the ci-ELISA had 76% recovery rate. When tested with CL-fed chicken muscle tissues, the protein microarray assay had higher sensitivity (0.9 ng/g than the ci-ELISA (0.1 ng/g for detection of CL residues. Conclusions The protein microarrays showed 4.5 and 3.5 times lower IC50 than the ci-ELISA detection for CL and SM2, respectively, suggesting that immunodetection of small molecules with protein microarray is a better approach than the traditional ELISA technique.

  17. Preparation and Properties of Agricultural Residuals-Iron Concentrate Pellets

    Directory of Open Access Journals (Sweden)

    Zhulin Liu

    2017-01-01

    Full Text Available In this paper, carbon-containing pellets were prepared by using crop-derived charcoal made from agricultural residuals and iron ore concentrates, and their pelletizing performance and properties were studied. Experimental results showed that the strengths of pellets were related to the particle size of concentrates and the content of moisture, bentonite, and crop-derived charcoal fines in the pelletizing mixture and the temperature of roasting and reduction. That the granularity of raw materials was fine and the bentonite content increased was beneficial to the improvement of pellet strengths. The suitable molar ratio of carbon to oxygen was 1.0 and the proper proportioning ratios of moisture and binder were 8.0% and 6.5%, respectively. The pellet strengths increased accordingly with increasing the reduction temperature, and when the temperature reached 1200°C, accompanied by the fast reduction of iron and the formation of crystal stock, the dropping strength of product pellets was 15 times and the compressive strength was 1650 N; this may be improved by grinding of the concentrate, leading to acceptable strength for the blast furnace.

  18. Novel in vitro systems for prediction of veterinary drug residues in ovine milk and dairy products.

    Science.gov (United States)

    González-Lobato, L; Real, R; Herrero, D; de la Fuente, A; Prieto, J G; Marqués, M M; Alvarez, A I; Merino, G

    2014-01-01

    A new in vitro tool was developed for the identification of veterinary substrates of the main drug transporter in the mammary gland. These drugs have a much higher chance of being concentrated into ovine milk and thus should be detectable in dairy products. Complementarily, a cell model for the identification of compounds that can inhibit the secretion of drugs into ovine milk, and thus reduce milk residues, was also generated. The ATP-binding cassette transporter G2 (ABCG2) is responsible for the concentration of its substrates into milk. The need to predict potential drug residues in ruminant milk has prompted the development of in vitro cell models over-expressing ABCG2 for these species to detect veterinary drugs that interact with this transporter. Using these models, several substrates for bovine and caprine ABCG2 have been found, and differences in activity between species have been reported. However, despite being of great toxicological relevance, no suitable in vitro model to predict substrates of ovine ABCG2 was available. New MDCKII and MEF3.8 cell models over-expressing ovine ABCG2 were generated for the identification of substrates and inhibitors of ovine ABCG2. Five widely used veterinary antibiotics (marbofloxacin, orbifloxacin, sarafloxacin, danofloxacin and difloxacin) were discovered as new substrates of ovine ABCG2. These results were confirmed for the bovine transporter and its Y581S variant using previously generated cell models. In addition, the avermectin doramectin was described as a new inhibitor of ruminant ABCG2. This new rapid assay to identify veterinary drugs that can be concentrated into ovine milk will potentially improve detection and monitoring of veterinary drug residues in ovine milk and dairy products.

  19. A simulation model for the prediction of tissue:plasma partition coefficients for drug residues in natural casings.

    Science.gov (United States)

    Haritova, Aneliya Milanova; Fink-Gremmels, Johanna

    2010-09-01

    Tissue residues arise from the exposure of animals to undesirable substances in animal feed materials and drinking water and to the therapeutic or zootechnical use of veterinary medicinal products. In the framework of this study, an advanced toxicokinetic model was developed to predict the likelihood of residue disposition of licensed veterinary products in natural casings used as envelope for a variety of meat products, such as sausages. The model proved suitable for the calculation of drug concentrations in the muscles of pigs, cattle and sheep, the major species of which intestines are used. On the basis of drug concentrations in muscle tissue, the model allowed a prediction of intestinal concentrations and residues in the intestines that remained equal to or below the concentrations in muscle tissue, the major consumable product of slaughter animals. Subsequently, residues in intestines were found to be below the maximum residue limit value for muscle tissue when drugs were used according to prescribed procedures, including the application of appropriate withdrawal times. Considering the low consumption of natural casings (which represents only about 1-2% of the weight of a normal sausage), it was concluded that the exposure to drug residues from casings is negligible. Copyright 2009 Elsevier Ltd. All rights reserved.

  20. Assessment of antibacterial drug residues in milk for consumption in Kosovo.

    Science.gov (United States)

    Rama, Adem; Lucatello, Lorena; Benetti, Cristiana; Galina, Guglielmo; Bajraktari, Drita

    2017-07-01

    The objective of this study was to assess the occurrence of drug residues in the raw milk collected from individual farms and milk collection points during 2009-2010 in six different major regions of Kosovo (Prishtinë, Gjilan, Mitrovicë, Pejë, Gjakovë, Prizren). In the present study, a total of 1734 raw milk samples were collected, and qualitatively screened with two different tests, the Delvotest SP assay and an enzyme-linked receptor-binding assay (SNAP). Overall, 106 (6.11%) out of 1734 samples examined with Delvotest SP contained possible drug residues (5.12% and 7.51% of samples from 2009 and 2010, respectively). All suspect samples were further analyzed by three distinct enzyme-linked receptor-binding assays specific for β-lactams (new β-lactam test), tetracyclines (SNAP tetracycline test), and sulfonamides (SNAP sulfamethazine test). Only the new SNAP β-lactam test detected residues in 40 out of 52 samples in 2009 and 54 out of 54 suspect samples in 2010. A confirmatory method based on liquid chromatography-tandem mass spectrometry was used to confirm the presence of β-lactam drug residues in samples detected by the enzyme-linked receptor-binding assay. Amoxicillin, penicillin G, and cloxacillin were the most frequently detected residues and were in a concentration range between 2.1 μg/kg and 1973 μg/kg. Seventeen of the positive samples exceeded the maximum residue levels for one or more β-lactam drug. The highest number of positive milk samples came from the Pejë Region (58.8%) and Gjakovë Region (23.5%), and the lowest number of positive samples originated from Gjilan (5.88%), with no positive samples detected in two regions, Mitrovicë and Prizren. Copyright © 2016. Published by Elsevier B.V.

  1. Rapid Methods for detection of Veterinary Drug residues in Meat

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    Chandan

    2010-10-01

    Full Text Available The use of substances having hormonal or thyreostatic action as well as b-agonists is banned in many countries. However, sometimes forbidden drugs may be added to feeds for illegal administration to farm animals for promoting increased muscle development or increased water retention and thus obtain an economical benefit. The result is a fraudulent overweight of meat but, what is worse, residues of these substances may remain in meat and may pose a real threat to the consumer either through exposure to the residues, transfer of antibiotic resistance or allergy risk. This has exerted a great concern among the meat consumers. The control of the absence of these forbidden substances in animal foods and feeds is regulated in the European Union by Directive 96/23/EC on measures to monitor certain substances and residues in live animals and animal products. Analytical methodology, including criteria for identification and confirmation, for the monitoring of compliance was also given in Decisions 93/256/EEC and 93/257/EEC. More recently, Decision 2002/657/EC provided rules for the analytical methods to be used in testing of official samples. New substances with anabolic properties are being detected year by year increasing the list of forbidden compounds to be tested. Furthermore, the extended practice consisting in the use of “cocktails” (mixtures of low amounts of several substances that exert a synergistic effect to have a similar growth promotion, reduces the margin for an effective analytical detection. Thus, the evolution of the “black market” is making really difficult to have an effective analytical control of the residues of these substances in foods of animal origin. Control laboratories must face an increasing demand of analysis like the growing number of residues to be analysed in different types of samples, the strict guidelines for analytical methodologies according to the latest Directives, the increased costs of such new

  2. [A smear method for measuring anti-cancer drugs residues in hospitals].

    Science.gov (United States)

    Takano, Takumi; Suzuki, Shigeru; Tsukiyama, Ikuto; Saito, Hiroko

    2015-01-01

    Anti-cancer drugs are harmful to healthy persons. In recent years, occupational exposure to anti-cancer drugs has become a major concern to health care workers. To address this issue, a smear method was developed to measure widely using anti-cancer drugs depositing on the floors, safety cabinet surfaces, and tables in hospital. Ten kinds of widely used anti-cancer drugs, paclitaxel, vincristine, docetaxel, vinorelbine, irinotecan, methotrexate, oxaliplatin, cyclophosphamide, gemcitabine and fluorouracil were collected by smearing material surfaces with methanol impregnated cellulose filter paper and/or polypropylene nonwoven. The collected anti-cancer drugs are extracted in 5 ml of 0.01% (v/v) hydrazine/methanol solution by sonication. The extracted solution was filtered and concentrated to prepare 1ml of sample solution. Then, the anti-cancer drugs in the sample solution were simultaneously measured by LC/MS. The anti-cancer drugs excepting fluorouracil spread on P-tile surface were measured with recoveries of 37-101% and standard deviations (SD) of 1.8-19%. All 10 of the anti-cancer drugs on a stainless steel plate surface were measured with the recoveries of 35-111% and SD of 1.3-11%. Using this smear method, 9 or 10 kinds of widely used anti-cancer drug residues in hospital, possibly exposed to health care workers, were grasped.

  3. 75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Science.gov (United States)

    2010-08-03

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-D-0246] Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...

  4. Variability of residue concentrations of ciprofloxacin in honey from treated hives.

    Science.gov (United States)

    Chan, Danny; Macarthur, Roy; Fussell, Richard J; Wilford, Jack; Budge, Giles

    2017-04-01

    Honey bees (Apis mellifera L.) were treated with a model veterinary drug compound (ciprofloxacin) in a 3-year study (2012-14) to investigate the variability of residue concentration in honey. Sucrose solution containing ciprofloxacin was administered to 45 hives (1 g of ciprofloxacin per hive) at the beginning of the honey flow in late May/mid-June 2012, 2013 and 2014. Buckfast honey bees (A. mellifera - hybrid) were used in years 2012 and 2013. Carniolan honey bees (A. mellifera carnica) were used instead of the Buckfast honey bees as a replacement due to unforeseen circumstances in the final year of the study (2014). Honey was collected over nine scheduled time points from May/June till late October each year. Up to five hives were removed and their honey analysed per time point. Honey samples were analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine ciprofloxacin concentration. Statistical assessment of the data shows that the inter-hive variation of ciprofloxacin concentrations in 2012/13 is very different compared with that of 2014 with relative standard deviations (RSDs) of 138% and 61%, respectively. The average ciprofloxacin concentration for 2014 at the last time point was more than 10 times the concentration compared with samples from 2012/13 at the same time point. The difference between the 2012/13 data compared with the 2014 data is likely due to the different type of honey bees used in this study (2012/13 Buckfast versus 2014 Carniolan). Uncertainty estimates for honey with high ciprofloxacin concentration (upper 95th percentile) across all hives for 55-day withdrawal samples gave residual standard errors (RSEs) of 22%, 20% and 11% for 2012, 2013 and 2014, respectively. If the number of hives were to be reduced for future studies, RSEs were estimated to be 52% (2012), 54% (2013) and 26% (2014) for one hive per time point (nine total hives).

  5. Minimizing residual aluminum concentration in treated water by tailoring properties of polyaluminum coagulants.

    Science.gov (United States)

    Kimura, Masaoki; Matsui, Yoshihiko; Kondo, Kenta; Ishikawa, Tairyo B; Matsushita, Taku; Shirasaki, Nobutaka

    2013-04-15

    Aluminum coagulants are widely used in water treatment plants to remove turbidity and dissolved substances. However, because high aluminum concentrations in treated water are associated with increased turbidity and because aluminum exerts undeniable human health effects, its concentration should be controlled in water treatment plants, especially in plants that use aluminum coagulants. In this study, the effect of polyaluminum chloride (PACl) coagulant characteristics on dissolved residual aluminum concentrations after coagulation and filtration was investigated. The dissolved residual aluminum concentrations at a given coagulation pH differed among the PACls tested. Very-high-basicity PACl yielded low dissolved residual aluminum concentrations and higher natural organic matter (NOM) removal. The low residual aluminum concentrations were related to the low content of monomeric aluminum (Ala) in the PACl. Polymeric (Alb)/colloidal (Alc) ratio in PACl did not greatly influence residual aluminum concentration. The presence of sulfate in PACl contributed to lower residual aluminum concentration only when coagulation was performed at around pH 6.5 or lower. At a wide pH range (6.5-8.5), residual aluminum concentrations residual aluminum concentrations did not increase with increasing the dosage of high-basicity PACl, but did increase with increasing the dosage of normal-basicity PACl. We inferred that increasing the basicity of PACl afforded lower dissolved residual aluminum concentrations partly because the high-basicity PACls could have a small percentage of Ala, which tends to form soluble aluminum-NOM complexes with molecular weights of 100 kDa-0.45 μm. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Multivariate concentration determination using principal component regression with residual analysis.

    Science.gov (United States)

    Keithley, Richard B; Heien, Michael L; Wightman, R Mark

    2009-10-01

    Data analysis is an essential tenet of analytical chemistry, extending the possible information obtained from the measurement of chemical phenomena. Chemometric methods have grown considerably in recent years, but their wide use is hindered because some still consider them too complicated. The purpose of this review is to describe a multivariate chemometric method, principal component regression, in a simple manner from the point of view of an analytical chemist, to demonstrate the need for proper quality-control (QC) measures in multivariate analysis and to advocate the use of residuals as a proper QC method.

  7. Plasma drug concentrations and physiological measures in 'dance party' participants.

    Science.gov (United States)

    Irvine, Rodney J; Keane, Michael; Felgate, Peter; McCann, Una D; Callaghan, Paul D; White, Jason M

    2006-02-01

    The increasing use of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) in the setting of large dance parties ('raves') and clubs has been the source of some concern, because of potential acute adverse events, and because animal studies suggest that MDMA has the potential to damage brain serotonin (5-HT) neurons. However, it is not yet known whether MDMA, as used in the setting of dance parties, leads to plasma levels of MDMA that are associated with toxicity to 5-HT neurons in animals. The present study sought to address this question. Plasma MDMA concentrations, vital signs, and a variety of blood and urine measures were obtained prior to, and hours after, individuals attended a dance party. After the dance party, subjects were without clinical complaints, had measurable amounts of residual MDMA in plasma, and nearly half of the subjects also tested positive for methamphetamine, another amphetamine analog that has been shown to have 5-HT neurotoxic potential in animals. Plasma concentrations of MDMA did not correlate with self-reported use of 'ecstasy' and, in some subjects, overlapped with those that have been associated with 5-HT neurotoxicity in non-human primates. Additional subjects were likely to have had similar concentrations while at the dance party, when one considers the reported time of drug ingestion and the plasma half-life of MDMA in humans. Hematological and biochemical analyses were generally unremarkable. Moderate increases in blood pressure, heart rate and body temperature were observed in the subjects with the highest MDMA plasma concentrations. These findings are consistent with epidemiological findings that most people who use MDMA at dance parties do not develop serious clinical complications, and suggest that some of these individuals may be at risk for developing MDMA-induced toxicity to brain serotonin neurons.

  8. Survey of Veterinary Drug Residues in Raw Milk in Hebei Province, China.

    Science.gov (United States)

    Han, Rong-Wei; Yu, Zhong-Na; Zhen, Tian-Yuan; Wang, Jun

    2017-10-17

    The objective of this study was to investigate the occurrence of veterinary drug residues in raw milk from Hebei, the second-largest dairy production province in the People's Republic of China. A total of 192 raw milk samples were collected from 64 milk stations in seven districts. Twenty-eight veterinary drug residues were analyzed by ultraperformance liquid chromatography with tandem mass spectrometry based on a China National Standard. Raw milk samples with multiple residues of veterinary drugs were not found in the present study. Residues of four veterinary drugs, penicillin G, sulfacetamide, trimethoprim, and lincomycin, were detected in 12 (6.25%) raw milk samples, with detection ratios of 1.04, 0.52, 3.13, and 1.56%, respectively. All veterinary drug residues detected were under the maximum residue levels as regulated by China, the European Union, the United States, and the Codex Alimentarius Commission. In general, raw milk from Hebei province was considered relatively safe for human consumption because of the low prevalence of veterinary drug residues. However, stringent control measurements for veterinary drug residues in raw milk are required because some veterinary drugs were detected in milk from some areas of Hebei province.

  9. A survey of chlortetracycline concentration in feed and its residue in ...

    Indian Academy of Sciences (India)

    2014-04-04

    Apr 4, 2014 ... Food Control 15 99–105. Kan C A and Petz M 2000 Residues of veterinary drugs in eggs and their distribution between yolk and white. J. Agri. Food Chem. 48 6397–6403. Kennedy DG, McCracken RJ, Hewitt SA and McEvoy JDG 1998. Metabolism of chlortetracycline: drug accumulation and excre-.

  10. Biogas from Agricultural Residues as Energy Source in Hybrid Concentrated Solar Power

    NARCIS (Netherlands)

    Corré, W.J.; Conijn, J.G.

    2016-01-01

    This paper explores the possibilities of sustainable biogas use for hybridisation of Concentrated Solar Power (HCSP) in Europe. The optimal system for the use of biogas from agricultural residues (manure and crop residues) in HCSP involves anaerobic digestion with upgrading of biogas to

  11. Analysis of spironolactone residues in industrial wastewater and in drug formulations by cathodic stripping voltammetry.

    Science.gov (United States)

    El-Shahawi, M S; Bashammakh, A S; Al-Sibaai, A A; Bahaidarah, E A

    2013-04-01

    The redox behavior of spironolactone (SP) drug in Britton-Robinson (BR) buffer of pH 2-11 was investigated by differential pulse cathodic stripping voltammetry (DPCSV) and cyclic voltammetry (CV) at hanging mercury dropping electrode (HMDE). At pH 9-10.5, the DPCSV of SP drug showed two cathodic peaks at -1.15 and -1.38 V at the HMDE vs. Ag/AgCl reference electrode. In the CV, at pH 9-10, the dependence of the cathodic peak current, I p , c and peak potential, E p , c of the second peak ( E p , c 2 ) on the scan rate ( ν ) and on the depolizer (SP) concentrations was typical of an electrode coupled (EC) chemical reaction type mechanism. The plot of I p , c at -1.380 V of the DPCSV vs. SP concentration at pH 9 was linear over the concentration range of 1.2×10 -10 -9.6×10 -7  M. The lower limit of detection (LLOD) and limit of quantification (LOQ) of the drug were 1.1×10 -11 and 4.14×10 -11  M, respectively. The method was successfully applied for the analysis of SP residues in industrial wastewater, in pure form (98.2±3.1%) and in drug formulations e.g. Aldactone® tablet (98.35±2.9%).The method was validated by comparison with HPLC and the official data methods.

  12. 75 FR 75482 - Draft Guidance for Industry on Residual Solvents in Animal Drug Products; Questions and Answers...

    Science.gov (United States)

    2010-12-03

    ... guidance for industry 211 entitled ``Residual Solvents in Animal Drug Products; Questions and Answers... availability of a draft guidance for industry 211 entitled ``Residual Solvents in Animal ] Drug Products... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Residual Solvents in Animal...

  13. 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) were...... selected as model drugs. Self-diffusion nuclear magnetic resonance studies were performed and confirmed the entrapment of drugs in micelles in Brij 35 and sodium taurodeoxycholate (TDC)/phosphatidylcholine (PC) micellar solutions. The FDS measurements indicated that with a constant level of drug...

  14. Database dedicated to information published during the Benelux conferences on hormone and veterinary drug residue analyses

    NARCIS (Netherlands)

    Impens, S.; Brabander, H.F. de; Bergwerff, A.A.; Ginkel, L.A. van; Schilt, R.; Stephany, R.W.; Wasch, K. de; Courtheyn, D.; Peteghem, C. van

    2002-01-01

    Every other year scientists working in the field of residue analysis participate the "International Symposium on Hormone and Veterinary Drug Residue Analysis" and "Euroresidue" conferences. In each symposium a lot of innovative information is presented. In order to obtain a retrieval system for this

  15. Development of irradiation technique on degradation residue of pesticide veterinary drugs and mycotoxins in food

    International Nuclear Information System (INIS)

    He Jiang; Huang Min; Chen Hao; Wu Ling; Gao Peng; Wang Yan; Lei Qing

    2012-01-01

    Irradiation technology is a new processing technology, It was widely used in food, medicines and medical supplies, chemical and other industries. In this paper, illustrated their applications in the degradation of pesticides, veterinary drugs and mycotoxins aspects residual pollution in food. Analysis of residual contaminants in food irradiation control study limitations and look forward to the prospect of food irradiation technology. (authors)

  16. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (French Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  17. Manual of Standard Operating Procedures for Veterinary Drug Residue Analysis (Spanish Edition)

    International Nuclear Information System (INIS)

    2017-01-01

    Laboratories are crucial to national veterinary drug residue monitoring programmes. However, one of the main challenges laboratories encounter is obtaining access to relevant methods of analysis. Thus, in addition to training, providing technical advice and transferring technology, the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture has resolved to develop clear and practical manuals to support Member State laboratories. The Coordinated Research Project (CRP) on Development of Radiometric and Allied Analytical Methods to Strengthen Residue Control Programs for Antibiotic and Anthelmintic Veterinary Drug Residues has developed a number of analytical methods as standard operating procedures (SOPs), which are now compiled here. This publication contains SOPs on chromatographic and spectrometric techniques, as well as radioimmunoassay and associated screening techniques, for various anthelmintic and antimicrobial veterinary drug residue analysis. Some analytical method validation protocols are also included. The publication is primarily aimed at food and environmental safety laboratories involved in testing veterinary drug residues, including under organized national residue monitoring programmes. It is expected to enhance laboratory capacity building and competence through the use of radiometric and complementary tools and techniques. The publication is also relevant for applied research on residues of veterinary drugs in food and environmental samples

  18. Residue analysis of veterinary drugs and growth-promoting agents

    NARCIS (Netherlands)

    Stolker, A.A.M.; Zuidema, T.; Nielen, M.W.F.

    2007-01-01

    Two major trends are observed in the analysis of veterinary drugs and growth-promoting agents. First is the selection of sample material for monitoring the use of registered veterinary drugs. Traditionally meat, kidney and liver were analyzed but, due to the food scandals in which meat was very

  19. Drug residues in urban water: A database for ecotoxicological risk management.

    Science.gov (United States)

    Destrieux, Doriane; Laurent, François; Budzinski, Hélène; Pedelucq, Julie; Vervier, Philippe; Gerino, Magali

    2017-12-31

    Human-use drug residues (DR) are only partially eliminated by waste water treatment plants (WWTPs), so that residual amounts can reach natural waters and cause environmental hazards. In order to properly manage these hazards in the aquatic environment, a database is made available that integrates the concentration ranges for DR, which cause adverse effects for aquatic organisms, and the temporal variations of the ecotoxicological risks. To implement this database for the ecotoxicological risk assessment (ERA database), the required information for each DR is the predicted no effect concentrations (PNECs), along with the predicted environmental concentrations (PECs). The risk assessment is based on the ratio between the PNECs and the PECs. Adverse effect data or PNECs have been found in the publicly available literature for 45 substances. These ecotoxicity test data have been extracted from 125 different sources. This ERA database contains 1157 adverse effect data and 287 PNECs. The efficiency of this ERA database was tested with a data set coming from a simultaneous survey of WWTPs and the natural environment. In this data set, 26 DR were searched for in two WWTPs and in the river. On five sampling dates, concentrations measured in the river for 10 DR could pose environmental problems of which 7 were measured only downstream of WWTP outlets. From scientific literature and measurements, data implementation with unit homogenisation in a single database facilitates the actual ecotoxicological risk assessment, and may be useful for further risk coming from data arising from the future field survey. Moreover, the accumulation of a large ecotoxicity data set in a single database should not only improve knowledge of higher risk molecules but also supply an objective tool to help the rapid and efficient evaluation of the risk. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Effect In Vitro of Antiparasitic Drugs on Microbial Inhibitor Test Responses for Screening Antibiotic Residues in Goat's Milk.

    Science.gov (United States)

    Romero, T; Beltrán, M C; Reybroeck, W; Molina, M P

    2015-09-01

    Microbial inhibitor tests are widely used to screen antibiotic residues in milk; however, these tests are nonspecific and may be affected by various substances capable of inhibiting the growth of the test microorganism. The objective of this study was to determine the effect of antiparasitic drugs in goat's milk on the microbial inhibitor test response. Raw antibiotic-free milk from Murciano-Granadina goats was supplemented with eight concentrations of seven antiparasitic substances (albendazole, 10 to 170 mg/kg; closantel, 1 to 140 mg/kg; diclazuril, 8 to 45 mg/kg; febendazole, 10 to 140 mg/kg; levamisole, 40 to 440 mg/kg; diazinon, 8 to 45 mg/kg; and ivermectin, 40 to 200 mg/kg). Twelve replicates for each concentration were analyzed with three microbial inhibitor tests: BRT MRL, Delvotest SP-NT MSC, and Eclipse 100. The results were interpreted visually (negative or positive). Using a logistic regression model, the concentrations of the antiparasitic drugs producing 5% (IC5), 10% (IC10), and 50% (IC50) positive results were determined. In general, the Eclipse 100 test was less sensitive to the effect of antiparasitic substances; the inhibitory concentrations of almost all the drugs assayed were higher than those for other tests. Conversely, the BRT MRL test was most affected, with high levels of interference at lower antiparasitic drug concentrations. Closantel and diazinon interfered with all microbial tests at lower concentrations than did other drugs (IC5 = 1 to 26 and 12 to 20 mg/kg, respectively), and higher concentrations of levamisole and diclazuril (IC5 = 30 to 240 and 50 to 117 mg/kg, respectively) were required to produce 5% positive results. These findings indicate that microbial inhibitor tests can be affected by elevated concentrations of antiparasitic drugs in goat's milk.

  1. Determination of residual dimethylsulphoxide in drug loaded gelatin using thermal desorber - gas chromatography.

    Science.gov (United States)

    Asfaw, Adissu Alemayehu; Wolfs, Kris; Van Schepdael, Ann; Adams, Erwin

    2018-05-10

    Traditional headspace - gas chromatography (HS-GC) methods for the determination of residual solvents (RS) start from a homogenous sample solution. Subsequently, it is challenging to determine RS using HS-GC techniques from insoluble solid samples like gelatin which is practically impossible to dissolve or distribute uniformly in water and common organic solvents. In this study, a thermal desorber combined with capillary gas chromatography and flame ionization detection/mass spectrometry (TD-GC-FID/MS) was used for quantitative determination of residual dimethylsulfoxide (DMSO) in gelatin without sample pretreatment. A sample of gelatin was sandwiched between two quartz filter double layers in a polytetrafluoroethylene insert which was then placed in its entirety into a thermal desorption tube. Factors affecting the performance of TD-GC including desorption time, desorption temperature, desorption flow and type of adsorbent were studied by applying a standard solution of DMSO in methanol on a blank gelatin bed. Validation results of the proposed method showed good linearity with an R 2 -value higher than 0.999 for a wide concentration range and good sensitivity with a limit of detection and limit of quantification of 0.1 μg and 0.2 μg on tube, respectively. The proposed method shows recovery values close to 100%. In addition, a conventional HS-GC method following enzymatic degradation of gelatin was developed to verify the proposed TD-GC method. Both methods were applied for the determination of residual DMSO in gelatin that was loaded with an experimental drug. Results were comparable, but the enzyme assisted HS-GC method was more time consuming and expensive. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. Residues of drugs | Oppong | Journal of the Ghana Science ...

    African Journals Online (AJOL)

    Our concern in this paper is with agricultural activities, specifically a number of livestock production techniques and the dangers they may pose to humans through their consumption of meat, milk, and fish. For drugs, pesticides, insecticides and hormones are variously used in animal production and some of these are ...

  3. Minimizing residual aluminum concentration in treated water by tailoring properties of polyaluminum coagulants

    OpenAIRE

    Kimura, Masaoki; Matsui, Yoshihiko; Kondo, Kenta; Ishikawa, Tairyo B.; Matsushita, Taku; Shirasaki, Nobutaka

    2013-01-01

    Aluminum coagulants are widely used in water treatment plants to remove turbidity and dissolved substances. However, because high aluminum concentrations in treated water are associated with increased turbidity and because aluminum exerts undeniable human health effects, its concentration should be controlled in water treatment plants, especially in plants that use aluminum coagulants. In this study, the effect of polyaluminum chloride (PACl) coagulant characteristics on dissolved residual al...

  4. Quantum Dots Applied to Methodology on Detection of Pesticide and Veterinary Drug Residues.

    Science.gov (United States)

    Zhou, Jia-Wei; Zou, Xue-Mei; Song, Shang-Hong; Chen, Guan-Hua

    2018-02-14

    The pesticide and veterinary drug residues brought by large-scale agricultural production have become one of the issues in the fields of food safety and environmental ecological security. It is necessary to develop the rapid, sensitive, qualitative and quantitative methodology for the detection of pesticide and veterinary drug residues. As one of the achievements of nanoscience, quantum dots (QDs) have been widely used in the detection of pesticide and veterinary drug residues. In these methodology studies, the used QD-signal styles include fluorescence, chemiluminescence, electrochemical luminescence, photoelectrochemistry, etc. QDs can also be assembled into sensors with different materials, such as QD-enzyme, QD-antibody, QD-aptamer, and QD-molecularly imprinted polymer sensors, etc. Plenty of study achievements in the field of detection of pesticide and veterinary drug residues have been obtained from the different combinations among these signals and sensors. They are summarized in this paper to provide a reference for the QD application in the detection of pesticide and veterinary drug residues.

  5. Drug residues and endocrine disruptors in drinking water: risk for humans?

    Science.gov (United States)

    Touraud, Evelyne; Roig, Benoit; Sumpter, John P; Coetsier, Clémence

    2011-11-01

    The presence of pharmaceuticals and endocrine disruptors in the environment raises many questions about risk to the environment and human health. Environmental exposure has been largely studied, providing to date a realistic picture of the degree of contamination of the environment by pharmaceuticals and hormones. Conversely, little information is available regarding human exposure. NSAIDS, carbamazepine, iodinated contrast media, β-blockers, antibiotics have been detected in drinking water, mostly in the range of ng/L. it is questioned if such concentrations may affect human health. Currently, no consensus among the scientific community exists on what risk, if any, pharmaceuticals and endocrine disruptors pose to human health. Future European research will focus, on one hand, on genotoxic and cytotoxic anti-cancer drugs and, on the other hand, on the induction of genetic resistance by antibiotics. This review does not aim to give a comprehensive overview of human health risk of drug residues and endocrine disruptors in drinking water but rather highlight important topics of discussion. Copyright © 2011. Published by Elsevier GmbH.

  6. Determination of residual ractopamine concentrations by enzyme immunoassay in treated pig's tissues on days after withdrawal.

    Science.gov (United States)

    Pleadin, Jelka; Perši, Nina; Vulić, Ana; Milić, Dinka; Vahčić, Nada

    2012-03-01

    The objective of this study was to measure residual ractopamine concentrations in tissues of pigs as experimental animals after treatment with dietary ractopamine for 28 consecutive days. Ractopamine was administered orally to the experimental group (n=9) in a dose of 0.1mg/kg body mass per day, whereas control animals (n=3) were left untreated. Treated pigs (60kg) were sacrificed on days 1, 3 and 8 of treatment discontinuation and residues were determined in kidney, liver, muscle, brain and heart tissues using previously validated enzyme-linked immunosorbent assay (ELISA) as a quantitative screening method. Validation showed good mean recoveries (approx. 70-90%) with acceptable inter- and intra-day relative standard deviations (RSDractopamine tissue concentrations. The highest ractopamine concentration on day 1 (24h) after the last exposure was recorded in the kidney (12.49±7.96ng/g), followed by the liver (7.21±2.73ng/g), heart (1.26±0.12ng/g) and brain (0.63±0.05ng/g); at this time of withdrawal, residues were not detected in the muscle. Ractopamine was depleted rapidly from all study tissues, with mostly no detectable residues on day 8 of withdrawal. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. The residual C concentration control for low temperature growth p-type GaN

    International Nuclear Information System (INIS)

    Liu Shuang-Tao; Zhao De-Gang; Yang Jing; Jiang De-Sheng; Liang Feng; Chen Ping; Zhu Jian-Jun; Liu Zong-Shun; Li Xiang; Liu Wei; Xing Yao; Zhang Li-Qun

    2017-01-01

    In this work, the influence of C concentration to the performance of low temperature growth p-GaN is studied. Through analyses, we have confirmed that the C impurity has a compensation effect to p-GaN. At the same time we have found that several growth and annealing parameters have influences on the residual C concentration: (i) the C concentration decreases with the increase of growth pressure; (ii) we have found there exists a Ga memory effect when changing the Cp 2 Mg flow which will lead the growth rate and C concentration increase along the increase of Cp 2 Mg flow; (iii) annealing outside of metal–organic chemical vapor deposition (MOCVD) could decrease the C concentration while in situ annealing in MOCVD has an immobilization role to C concentration. (paper)

  8. 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

  9. Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

    Science.gov (United States)

    Tomar, Dheeraj S; Kumar, Sandeep; Singh, Satish K; Goswami, Sumit; Li, Li

    2016-01-01

    Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored.

  10. Uncertainty of pesticide residue concentration determined from ordinary and weighted linear regression curve.

    Science.gov (United States)

    Yolci Omeroglu, Perihan; Ambrus, Árpad; Boyacioglu, Dilek

    2018-03-28

    Determination of pesticide residues is based on calibration curves constructed for each batch of analysis. Calibration standard solutions are prepared from a known amount of reference material at different concentration levels covering the concentration range of the analyte in the analysed samples. In the scope of this study, the applicability of both ordinary linear and weighted linear regression (OLR and WLR) for pesticide residue analysis was investigated. We used 782 multipoint calibration curves obtained for 72 different analytical batches with high-pressure liquid chromatography equipped with an ultraviolet detector, and gas chromatography with electron capture, nitrogen phosphorus or mass spectrophotometer detectors. Quality criteria of the linear curves including regression coefficient, standard deviation of relative residuals and deviation of back calculated concentrations were calculated both for WLR and OLR methods. Moreover, the relative uncertainty of the predicted analyte concentration was estimated for both methods. It was concluded that calibration curve based on WLR complies with all the quality criteria set by international guidelines compared to those calculated with OLR. It means that all the data fit well with WLR for pesticide residue analysis. It was estimated that, regardless of the actual concentration range of the calibration, relative uncertainty at the lowest calibrated level ranged between 0.3% and 113.7% for OLR and between 0.2% and 22.1% for WLR. At or above 1/3 of the calibrated range, uncertainty of calibration curve ranged between 0.1% and 16.3% for OLR and 0% and 12.2% for WLR, and therefore, the two methods gave comparable results.

  11. [Residues of organochlorine compounds in plant drugs. 1. Gas chromatographic determination of residues of organochlorine insecticides].

    Science.gov (United States)

    Benecke, R; Thieme, H; Brotka, J

    1986-02-01

    A method for the identification and determination of HCH-and DDT-isomers and their respective metabolites in vegetable drugs is presented. The plant material is extracted with hexane in a Soxhlet apparatus in the presence of silicagel and sodium sulfate. For removing interfering endogenous plant constituents a Celite oleum column cleanup and usually and acetonitrile partitioning to follow are necessary. A mixed stationary phase OV-17/QF-1 has proved effective for the gc separation on packed columns. 3H-ECD is used for detection. For the quantitative determination by using an external standard the peak height measurement is recommended. Recoveries of all insecticides were in the order of 70-105% with coefficients of variation between 6 and 20%. To ensure the results the alkaline treatment and oxidation of extracts are proposed.

  12. Estimation of the residual bromine concentration after disinfection of cooling water by statistical evaluation.

    Science.gov (United States)

    Megalopoulos, Fivos A; Ochsenkuehn-Petropoulou, Maria T

    2015-01-01

    A statistical model based on multiple linear regression is developed, to estimate the bromine residual that can be expected after the bromination of cooling water. Make-up water sampled from a power plant in the Greek territory was used for the creation of the various cooling water matrices under investigation. The amount of bromine fed to the circuit, as well as other important operational parameters such as concentration at the cooling tower, temperature, organic load and contact time are taken as the independent variables. It is found that the highest contribution to the model's predictive ability comes from cooling water's organic load concentration, followed by the amount of bromine fed to the circuit, the water's mean temperature, the duration of the bromination period and finally its conductivity. Comparison of the model results with the experimental data confirms its ability to predict residual bromine given specific bromination conditions.

  13. Predicting the concentration of residual methanol in industrial formalin using machine learning

    OpenAIRE

    Heidkamp, William

    2016-01-01

    In this thesis, a machine learning approach was used to develop a predictive model for residual methanol concentration in industrial formalin produced at the Akzo Nobel factory in Kristinehamn, Sweden. The MATLABTM computational environment supplemented with the Statistics and Machine LearningTM toolbox from the MathWorks were used to test various machine learning algorithms on the formalin production data from Akzo Nobel. As a result, the Gaussian Process Regression algorithm was found to pr...

  14. On measurements of Effective Residual Ink Concentration (ERIC) of deinked papers using Kubelka-Munk theory

    Science.gov (United States)

    D.W. Vahey; J.Y. Zhu; C.J. Houtman

    2006-01-01

    The measurement of effective residual ink concentration (ERIC) in recycled papers depends on their opacity. For opacity less than 97.0%, the method is based on application of the Kubelka-Munk theory to diffuse reflection from papers measured once with a black backing and again with a thick backing of the same papers. At opacities above 97.0%, the two reflection values...

  15. 77 FR 3653 - Import Tolerances for Residues of Unapproved New Animal Drugs in Food

    Science.gov (United States)

    2012-01-25

    ... find a safe import tolerance. It could look at toxicity and residue data and build in a conservative... drugs covered by import tolerances are manufactured under good manufacturing practices (GMP)-like... resistant bacteria in or on the target animal and the potential impact on human health. C. International...

  16. 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.

  17. Surface wipe sampling for antineoplastic (chemotherapy) and other hazardous drug residue in healthcare settings: Methodology and recommendations.

    Science.gov (United States)

    Connor, Thomas H; Zock, Matthew D; Snow, Amy H

    2016-09-01

    Surface wipe sampling for various hazardous agents has been employed in many occupational settings over the years for various reasons such as evaluation of potential dermal exposure and health risk, source determination, quality or cleanliness, compliance, and others. Wipe sampling for surface residue of antineoplastic and other hazardous drugs in healthcare settings is currently the method of choice to determine surface contamination of the workplace with these drugs. The purpose of this article is to review published studies of wipe sampling for antineoplastic and other hazardous drugs, to summarize the methods in use by various organizations and researchers, and to provide some basic guidance for conducting surface wipe sampling for these drugs in healthcare settings.  Recommendations on wipe sampling methodology from several government agencies and organizations were reviewed. Published reports on wipe sampling for hazardous drugs in numerous studies were also examined. The critical elements of a wipe sampling program and related limitations were reviewed and summarized.  Recommendations and guidance are presented concerning the purposes of wipe sampling for antineoplastic and other hazardous drugs in the healthcare setting, technical factors and variables, sampling strategy, materials required, and limitations. The reporting and interpretation of wipe sample results is also discussed.  It is recommended that all healthcare settings where antineoplastic and other hazardous drugs are handled consider wipe sampling as part of a comprehensive hazardous drug "safe handling" program. Although no standards exist for acceptable or allowable surface concentrations for these drugs in the healthcare setting, wipe sampling may be used as a method to characterize potential occupational dermal exposure risk and to evaluate the effectiveness of implemented controls and the overall safety program. A comprehensive safe-handling program for antineoplastic drugs may

  18. Development of Analytical Method and Monitoring of Veterinary Drug Residues in Korean Animal Products.

    Science.gov (United States)

    Song, Jae-Sang; Park, Su-Jeong; Choi, Jung-Yun; Kim, Jin-Sook; Kang, Myung-Hee; Choi, Bo-Kyung; Hur, Sun Jin

    2016-01-01

    This study was conducted to determine the residual amount of veterinary drugs such as meloxicam, flunixin, and tulathromycin in animal products (beef, pork, horsemeat, and milk). Veterinary drugs have been widely used in the rearing of livestock to prevent and treat diseases. A total of 152 samples were purchased from markets located in major Korean cities (Seoul, Busan, Incheon, Daegu, Daejeon, Gwangju, Ulsan and Jeju), including Jeju. Veterinary drugs were analyzed by liquid chromatography-tandem mass spectrometry according to the Korean Food Standards Code. The resulting data, which are located within 70-120% of recovery range and less than 20% of relative standard deviations, are in compliance with the criteria of CODEX. A total of five veterinary drugs were detected in 152 samples, giving a detection rate of approximately 3.3%; and no food source violated the guideline values. Our result indicated that most of the veterinary drug residues in animal products were below the maximum residue limits specified in Korea.

  19. Effect of Residue Nitrogen Concentration and Time Duration on Carbon Mineralization Rate of Alfalfa Residues in Regions with Different Climatic Conditions

    Directory of Open Access Journals (Sweden)

    saeid shafiei

    2017-08-01

    Full Text Available Introduction Various factors like climatic conditions, vegetation, soil properties, topography, time, plant residue quality and crop management strategies affect the decomposition rate of organic carbon (OC and its residence time in soil. Plant residue management concerns nutrients recycling, carbon recycling in ecosystems and the increasing CO2 concentration in the atmosphere. Plant residue decomposition is a fundamental process in recycling of organic matter and elements in most ecosystems. Soil management, particularly plant residue management, changes soil organic matter both qualitatively and quantitatively. Soil respiration and carbon loss are affected by soil temperature, soil moisture, air temperature, solar radiation and precipitation. In natural agro-ecosystems, residue contains different concentrations of nitrogen. It is important to understand the rate and processes involved in plant residue decomposition, as these residues continue to be added to the soil under different weather conditions, especially in arid and semi-arid climates. Material and methods Organic carbon mineralization of alfalfa residue with different nitrogen concentrations was assessed in different climatic conditions using split-plot experiments over time and the effects of climate was determined using composite analysis. The climatic conditions were classified as warm-arid (Jiroft, temperate arid (Narab and cold semi-arid (Sardouiyeh using cluster analysis and the nitrogen (N concentrations of alfalfa residue were low, medium and high. The alfalfa residue incubated for four different time periods (2, 4, 6 and 8 months. The dynamics of organic carbon in different regions measured using litter bags (20×10 cm containing 20 g alfalfa residue of 2-10 mm length which were placed on the soil surface. Results and discussion The results of this study showed that in a warm-arid (Jiroft, carbon loss and the carbon decomposition rate constant were low in a cold semi

  20. A method for assessing residual NAPL based on organic chemical concentrations in soil samples

    International Nuclear Information System (INIS)

    Feenstra, S.; Mackay, D.M.; Cherry, J.A.

    1991-01-01

    Ground water contamination by non-aqueous phase liquid (NAPL) chemicals is a serious concern at many industrial facilities and waste disposal sites. NAPL in the form of immobile residual contamination, or pools of mobile or potentially mobile NAPL, can represent continuing sources of ground water contamination. In order to develop rational and cost-effective plans for remediation of soil and ground water contamination at such sites, it is essential to determine if non-aqueous phase liquid (NAPL) chemicals are present in the subsurface and delineate the zones of NAPL contamination. Qualitatively, soil analyses that exhibit chemical concentrations in the percent range or >10,000 mg/kg would generally be considered to indicate the presence of NAPL. However, the results of soil analyses are seldom used in a quantitative manner to assess the possible presence of residual NAPL contamination when chemical concentrations are lower and the presence of NAPL is not obvious. The assessment of the presence of NAPL in soil samples is possible using the results of chemical and physical analyses of the soil, and the fundamental principles of chemical partitioning in unsaturated or saturated soil. The method requires information on the soil of the type typically considered in ground water contamination studies and provides a simple tool for the investigators of chemical spill and waste disposal sites to assess whether soil chemical analyses indicate the presence of residual NAPL in the subsurface

  1. An Overview on Recent Progress in Electrochemical Biosensors for Antimicrobial Drug Residues in Animal-Derived Food

    Science.gov (United States)

    Majdinasab, Marjan; Yaqub, Mustansara; Rahim, Abdur; Catanante, Gaelle; Hayat, Akhtar; Marty, Jean Louis

    2017-01-01

    Anti-microbial drugs are widely employed for the treatment and cure of diseases in animals, promotion of animal growth, and feed efficiency. However, the scientific literature has indicated the possible presence of antimicrobial drug residues in animal-derived food, making it one of the key public concerns for food safety. Therefore, it is highly desirable to design fast and accurate methodologies to monitor antimicrobial drug residues in animal-derived food. Legislation is in place in many countries to ensure antimicrobial drug residue quantities are less than the maximum residue limits (MRL) defined on the basis of food safety. In this context, the recent years have witnessed a special interest in the field of electrochemical biosensors for food safety, based on their unique analytical features. This review article is focused on the recent progress in the domain of electrochemical biosensors to monitor antimicrobial drug residues in animal-derived food. PMID:28837093

  2. 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

    .We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence...... to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity.......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...

  3. Effect of six different starter cultures on the concentration of residual nitrite in fermented sausages during in vitro human digestion.

    Science.gov (United States)

    Kim, Hyeong Sang; Hur, Sun Jin

    2018-01-15

    The objective of this study was to determine the effect of six different starter cultures of enterobacteria on the concentration of residual nitrite in fermented sausages during in vitro human digestion. Before digestion, the concentration of residual nitrite was dependent on starter culture in fermented sausage and ranged from 25.2 to 33.2mg/kg. Among the six starter cultures of enterobacteria, Pediococcus acidilactici, Pediococcus pentosaceus, and Staphylococcus carnosus showed higher nitrite depletion ability than the other three strains in fermented sausages. The concentration of residual nitrite in fermented sausages was significantly (psausages. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Multi-residue determination of 115 veterinary drugs and pharmaceutical residues in milk powder, butter, fish tissue and eggs using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Dasenaki, Marilena E; Thomaidis, Nikolaos S

    2015-06-23

    A simple and sensitive multi-residue method for the determination of 115 veterinary drugs and pharmaceuticals, belonging in more than 20 different classes, in butter, milk powder, egg and fish tissue has been developed. The method involves a simple generic solid-liquid extraction step (solvent extraction, SE) with 0.1% formic acid in aqueous solution of EDTA 0.1% (w/v)-acetonitrile (ACN)-methanol (MeOH) (1:1:1, v/v) with additional ultrasonic-assisted extraction. Precipitation of lipids and proteins was promoted by subjecting the extracts at very low temperature (-23°C) for 12h. Further cleanup with hexane ensures fat removal from the matrix. Analysis was performed by liquid chromatography coupled with electrospray ionization and tandem mass spectrometry (LC-ESI-MS/MS). Two separate runs were performed for positive and negative ionization in multiple reaction monitoring mode (MRM). Particular attention was devoted to extraction optimization: different sample-to-extracting volume ratios, different concentrations of formic acid in the extraction solvent and different ultrasonic extraction temperatures were tested in butter, egg and milk powder samples. The method was also applied in fish tissue samples. It was validated, on the basis of international guidelines, for all four matrices. Quantitative analysis was performed by means of standard addition calibration. For over 80% of the analytes, the recoveries were between 50% and 120% in all matrices studied, with RSD values in the range of 1-18%. Limits of detection (LODs) and quantification (LOQs) ranged from 0.008 μg kg(-1) (oxfendazole in butter) to 3.15 μg kg(-1) (hydrochlorthiazide in egg). The evaluated method provides reliable screening, quantification, and identification of 115 veterinary drug and pharmaceutical residues in foods of animal origin and has been successfully applied in real samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Norepinephrine transporter function and desipramine: residual drug effects versus short-term regulation.

    Science.gov (United States)

    Ordway, Gregory A; Jia, Weihong; Li, Jing; Zhu, Meng-Yang; Mandela, Prashant; Pan, Jun

    2005-04-30

    Previous research has shown that exposure of norepinephrine transporter (NET)-expressing cells to desipramine (DMI) downregulates the norepinephrine transporter, although changes in the several transporter parameters do not demonstrate the same time course. Exposures to desipramine for effects of residual desipramine on norepinephrine transporter binding and uptake were re-evaluated following exposures of PC12 cells to desipramine using different methods to remove residual drug. Using a method that minimizes residual drug, exposure of intact PC12 cells to desipramine for 4h had no effect on uptake capacity or [(3)H]nisoxetine binding to the norepinephrine transporter, while exposures for > or =16 h reduced uptake capacity. Desipramine-induced reductions in binding to the transporter required >24 h or greater periods of desipramine exposure. This study confirms that uptake capacity of the norepinephrine transporter is reduced earlier than changes in radioligand binding, but with a different time course than originally shown. Special pre-incubation procedures are required to abolish effects of residual transporter inhibitor when studying inhibitor-induced transporter regulation.

  6. [Multi-residue method for determination of veterinary drugs and feed additives in meats by HPLC].

    Science.gov (United States)

    Chonan, Takao; Fujimoto, Toru; Ueno, Ken-Ichi; Tazawa, Teijiro; Ogawa, Hiroshi

    2007-10-01

    A simple and rapid multi-residue method was developed for the determination of 28 kinds of veterinary drugs and feed additives (drugs) in muscle of cattle, pig and chicken. The drugs were extracted with acetonitrile-water (95:5) in a homogenizer and ultrasonic generator. The extracted solution was poured into an alumina column and the drugs were eluted with acetonitrile-water (90:10). The eluate was washed with n-hexane saturated with acetonitrile and then evaporated. The drugs were separated on a Inertsil ODS-3V column (4.6 mm i.d. x 250 mm) with a gradient system of 0.1% phosphoric acid-acetonitrile as the mobile phase, with monitoring at 280 and 340 nm. The recoveries of the 26 kinds of drugs were over 60% from the meats fortified at 0.1 microg/g, and the quantification limits of most drugs were 0.01 microg/g. This proposed method was found to be effective and suitable for the screening of the above drugs in meats.

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

    Science.gov (United States)

    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

    2013-06-01

    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.We recommend drug concentration for skin testing aiming to achieve a specificity of at least 95%. It has been possible to recommend specific drug concentration for betalactam antibiotics, perioperative drugs, heparins, platinum salts and radiocontrast media. For many other drugs, there is insufficient evidence to recommend appropriate drug concentration. There is urgent need for multicentre studies designed to establish and validate drug skin test concentration using standard protocols. For most drugs, sensitivity of skin testing is higher in immediate hypersensitivity compared to nonimmediate hypersensitivity. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. A new one-platform flow cytometric method for residual cell counting in platelet concentrates.

    Science.gov (United States)

    Schmidt, Michael; Spengler, Hans-Peter; Lambrecht, Bernd; Hourfar, Michael K; Seifried, Erhard; Tonn, Torsten

    2009-12-01

    According to German regulations and guidelines, residual red blood cells (rRBCs) and residual white blood cells (rWBCs) must number fewer than 3 x 10(9) cells/unit and 1 x 10(6) cells/unit in platelet concentrates (PCs), respectively. Due to low levels of residual cells in final products, there is still a need for fast, reliable, and sensitive methods of automated detection of these cell types. In Part A, 21 PCs were spiked with predetermined numbers of red blood cells (RBCs) and white blood cells (WBCs). The linearity, precision, and accuracy of the BD Thrombo Count assay (BD Biosciences Europe) were tested and validated according to international guidelines. Finally in Part B, 100 PCs prepared from pooled buffy coats were tested by the BD Thrombo Count assay and compared with other methods, including Nageotte (rWBCs) and Neubauer (rRBCs) counting chambers and the flow cytometric BD LeucoCOUNT (Becton Dickinson) assay (rWBCs). The unspecific background of blank PC samples was fewer than 0.02 cells/microL for WBCs and fewer than 34 cells/microL for RBCs (mean, 21). Linear regression and precision analyses of spiked PC samples were determined for both WBCs (r(2) = 0.992; range, 0.6-6.0 WBCs/microL) and RBCs (r(2) = 0.999; 800-8000 RBCs/microL). No carryover of cells or drift in results was detected in the automated sample acquisition mode. Analysis according to statistical methods of Bland and Altman demonstrated a high correlation between BD Thrombo Count and the Neubauer manual counting chamber. This novel flow cytometric test is a quick and reliable single-tube assay that has been demonstrated as a potential alternative for the existing manual microscopic counting procedures that are both time-consuming and laborious.

  9. Pink shrimp (P. brasiliensis and P. paulensis) residue: influence of extraction method on carotenoid concentration.

    Science.gov (United States)

    Mezzomo, Natália; Maestri, Bianca; dos Santos, Renata Lazzaris; Maraschin, Marcelo; Ferreira, Sandra R S

    2011-09-15

    The main residue from the shrimp processing is formed by head and carapace and represents from 40 to 50% (w/w) of the integral shrimp. The recovery of the carotenoid fraction from this residue stands for an alternative to increase its aggregated value. Therefore, the objective of this study was to use the pink shrimp waste as raw material to obtain carotenoid enriched extracts, evaluating different pre-treatments and extraction methods. The shrimp waste was supplied by a local public market (Florianópolis, SC, Brazil). The investigation of the different pre-treatments applied to the raw material shows that cooking associated with milling and drying produced the extract richest in carotenoid fraction. The extraction methods considered in this work were Soxhlet, maceration and ultrasound by means of different organic solvents and also a vegetable oil as solvent. The extracts were evaluated in terms of yield, carotenoid profile, total carotenoid content (TCC), UV-Visible scanning spectrophotometry and mid-Fourier transform infrared spectroscopy (FTIR). The results indicate that shrimp waste can provide carotenoid enriched extracts, particularly astaxanthin, in concentrations up to 252 μg(astaxanthin)g(extract)(-1). The most adequate solvents were acetone and hexane: isopropanol (50:50, v/v) used in the maceration procedure. The UV-Vis results revealed the presence of carotenoids and flavonoids in the extracts while the FTIR spectroscopy indicated the existence of fatty acids, proteins, and phenolics. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Arsenic Species in Chicken Breast: Temporal Variations of Metabolites, Elimination Kinetics, and Residual Concentrations.

    Science.gov (United States)

    Liu, Qingqing; Peng, Hanyong; Lu, Xiufen; Zuidhof, Martin J; Li, Xing-Fang; Le, X Chris

    2016-08-01

    Chicken meat has the highest per capita consumption among all meat types in North America. The practice of feeding 3-nitro-4-hydroxyphenylarsonic acid (Roxarsone, Rox) to chickens lasted for more than 60 years. However, the fate of Rox and arsenic metabolites remaining in chicken are poorly understood. We aimed to determine the elimination of Rox and metabolites from chickens and quantify the remaining arsenic species in chicken meat, providing necessary information for meaningful exposure assessment. We have conducted a 35-day feeding experiment involving 1,600 chickens, of which half were control and the other half were fed a Rox-supplemented diet for the first 28 days and then a Rox-free diet for the final 7 days. We quantified the concentrations of individual arsenic species in the breast meat of 229 chickens. Rox, arsenobetaine, arsenite, monomethylarsonic acid, dimethylarsinic acid, and a new arsenic metabolite, were detected in breast meat from chickens fed Rox. The concentrations of arsenic species, except arsenobetaine, were significantly higher in the Rox-fed than in the control chickens. The half-lives of elimination of these arsenic species were 0.4-1 day. Seven days after termination of Rox feeding, the concentrations of arsenite (3.1 μg/kg), Rox (0.4 μg/kg), and a new arsenic metabolite (0.8 μg/kg) were significantly higher in the Rox-fed chickens than in the control. Feeding of Rox to chickens increased the concentrations of five arsenic species in breast meat. Although most arsenic species were excreted rapidly when the feeding of Rox stopped, arsenic species remaining in the Rox-fed chickens were higher than the background levels. Liu Q, Peng H, Lu X, Zuidhof MJ, Li XF, Le XC. 2016. Arsenic species in chicken breast: temporal variations of metabolites, elimination kinetics, and residual concentrations. Environ Health Perspect 124:1174-1181; http://dx.doi.org/10.1289/ehp.1510530.

  11. Rapid detection of chlorpyrifos pesticide residue concentration in agro-product using Raman spectroscopy

    Science.gov (United States)

    Dhakal, Sagar; Peng, Yankun; Li, Yongyu; Chao, Kuanglin; Qin, Jianwei; Zhang, Leilei; Xu, Tianfeng

    2014-05-01

    Different chemicals are sprayed in fruits and vegetables before and after harvest for better yield and longer shelf-life of crops. Cases of pesticide poisoning to human health are regularly reported due to excessive application of such chemicals for greater economic benefit. Different analytical technologies exist to detect trace amount of pesticides in fruits and vegetables, but are expensive, sample destructive, and require longer processing time. This study explores the application of Raman spectroscopy for rapid and non-destructive detection of pesticide residue in agricultural products. Raman spectroscopy with laser module of 785 nm was used to collect Raman spectral information from the surface of Gala apples contaminated with different concentrations of commercially available organophosphorous (48% chlorpyrifos) pesticide. Apples within 15 days of harvest from same orchard were used in this study. The Raman spectral signal was processed by Savitzky-Golay (SG) filter for noise removal, Multiplicative Scatter Correction (MSC) for drift removal and finally polynomial fitting was used to eliminate the fluorescence background. The Raman spectral peak at 677 cm-1 was recognized as Raman fingerprint of chlorpyrifos. Presence of Raman peak at 677 cm-1 after fluorescence background removal was used to develop classification model (presence and absence of pesticide). The peak intensity was correlated with actual pesticide concentration obtained using Gas Chromatography and MLR prediction model was developed with correlation coefficient of calibration and validation of 0.86 and 0.81 respectively. Result shows that Raman spectroscopy is a promising tool for rapid, real-time and non-destructive detection of pesticide residue in agro-products.

  12. A Nitrogen-concentrated Phase in IA Iron Meteorite Acid Residue

    Science.gov (United States)

    Hashizume, K.; Sugiura, N.

    1993-07-01

    portion of nitrogen is released at 500 degrees C and 600 degrees C temperature fractions. Total nitrogen amounts and average delta^l5N values of the two acid residues are described in Table 1. Discussion and Summary: Sample "Can-1bn" is 3-4 times concentrated in nitrogen than "Call-2b," although its delta^15N value is within terrestrial range (0 < delta^15N < +20 per mil). Presently, we cannot deny the possibility that nitrogen in "Can-1bn" is dominated by terrestrial nitrogen, which may have been acquired during the acid treatment. Nevertheless, nitrogen isotope data of "Can-2b" suggests that indigenous nitrogen is indeed concentrated in the acid residue of Canyon Diablo. Bulk nitrogen isotope data of Canyon Diablo is reported to be delta^15N= -61.8 +- 10.4 per mil, N= 38.0 +- 155 ppm [2]. Therefore, delta^15N values of "Can-2b" can be resulted by a mixing of indigenous nitrogen and contaminating nitrogen. However, distinct delta^15N values of these two samples may indicate, in turn, that nitrogen isotopes in inclusions of Canyon Diablo are truly heterogeneous because carbon isotopes of graphite inclusions in IA iron meteorites seem to be heterogeneous [7]. Acknowledgments: We thank Dr. J.-I. Matsuda of Osaka University for providing samples and information on these samples. References: [1] Scott E. R. D. and Wasson J. T. (1975) Rev. Geophys. Space Sci., 13, 527-546. [2] Prombo C. A. and Clayton R. N. (1983) Meteoritics, 18, 377-379. [3] Franchi I. A. et al. (1988) Meteoritics, 22, 379-380. [4] Hashizume K. (1993) Doctor Thesis. [5] Murty S. V. S. et al. (1983) GCA, 47, 1061-1068. [6] Ogata Y. et al. (1990) In Abstract of the 1990 Annual Meeting of the Geochemical Society of Japan, 57. [7] Deines P. and Wickman F. E. (1973) GCA, 37, 1295-1319. Table 1 appears here in the hard copy.

  13. Estimation of human body concentrations of DDT from indoor residual spraying for malaria control

    International Nuclear Information System (INIS)

    Gyalpo, Tenzing; Fritsche, Lukas; Bouwman, Henk; Bornman, Riana; Scheringer, Martin; Hungerbühler, Konrad

    2012-01-01

    Inhabitants of dwellings treated with DDT for indoor residual spraying show high DDT levels in blood and breast milk. This is of concern since mothers transfer lipid-soluble contaminants such as DDT via breastfeeding to their children. Focusing on DDT use in South Africa, we employ a pharmacokinetic model to estimate DDT levels in human lipid tissue over the lifetime of an individual to determine the amount of DDT transferred to children during breastfeeding, and to identify the dominant DDT uptake routes. In particular, the effects of breastfeeding duration, parity, and mother's age on DDT concentrations of mother and infant are investigated. Model results show that primiparous mothers have greater DDT concentrations than multiparous mothers, which causes higher DDT exposure of first-born children. DDT in the body mainly originates from diet. Generally, our modeled DDT levels reproduce levels found in South African biomonitoring data within a factor of 3. - Highlights: ► Comparison of one-compartment pharmacokinetic model with biomonitoring data. ► Pre- and postnatal exposure of infants depends on breastfeeding duration and parity. ► Dietary exposure of DDT is the dominant uptake route in South Africa. ► Elimination half-lives of DDT and DDE are shorter in children than in adults. - Model predictions of a one-compartment pharmacokinetic model confirm the trends of DDT found in human samples of inhabitants living in DDT-treated dwellings.

  14. Evaluation of droplet digital PCR for quantification of residual leucocytes in red blood cell concentrates.

    Science.gov (United States)

    Doescher, A; Loges, U; Petershofen, E K; Müller, T H

    2017-11-01

    Enumeration of residual white blood cells in leucoreduced blood components is essential part of quality control. Digital PCR has substantially facilitated quantitative PCR and was thus evaluated for measurements of leucocytes. Target for quantification of leucocytes by digital droplet PCR was the blood group gene RHCE. The SPEF1 gene was added as internal control for the entire assay starting with automated DNA extraction. The sensitivity of the method was determined by serial dilutions of standard samples. Quality control samples were analysed within 24 h, 7 days and 6 months after collection. Routine samples from leucodepleted red blood cell concentrates (n = 150) were evaluated in parallel by flow-cytometry (LeucoCount) and by digital PCR. Digital PCR reliably detected at least 0·4 leucocytes per assay. The mean difference between PCR and flow-cytometric results from 150 units was -0·01 (±1·0). DNA samples were stable for up to at least six months. PCR measurement of leucocytes in samples from plasma and platelet concentrates also provided valid results in a pilot study. Droplet digital PCR to enumerate leucocytes offers an alternative for quality control of leucoreduced blood products. Sensitivity, specificity and reproducibility are comparable to flow-cytometry. The option to collect samples over an extended period of time and the automatization introduce attractive features for routine quality control. © 2017 International Society of Blood Transfusion.

  15. Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015

    Directory of Open Access Journals (Sweden)

    Hsin-Chun Lee

    2018-04-01

    Full Text Available Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011–2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management. Keywords: Agricultural authorities, Livestock products, Post-market monitoring, Veterinary drug residues

  16. Determination of drug residues by CLAR-MS/MS in animal tissues

    International Nuclear Information System (INIS)

    Brenes Jimenez, Jose Eduardo

    2009-01-01

    Produced food of animal origin, present the possibility of occurrence of any contact with substances that have negative effects on the health of people who consume them. The use of drugs in veterinary medicine is one of the possible sources of such waste; so, the conditions for the analysis of some classes of antibiotics in animal tissues are based on the study. Costa Rica and the countries that are export destination, have regulation and programs for control before to be distributed in local markets, or post if it is received any complaint of pollution. The high resolution liquid chromatography coupled to mass spectrometers (CLAR-MS/MS) allows the analysis of analytes monitored, according to the specifications required by the legislation. The cases of two laboratories in Costa Rica are presented as the only ones who have the ability to perform the analysis of drug residues CLAR-MS/MS. (author) [es

  17. Organic co-solvent effect on the estimation of the equilibrium aqueous concentrations of oil residuals in Patagonian soil.

    Science.gov (United States)

    Nudelman, N S; Rios, S M; Katusich, O

    2002-09-01

    Determination of the equilibrium aqueous concentration and the distribution coefficients, K, in soil samples containing oil residuals of different age, was carried out using an organic co-solvent (methanol). It was found that the solvophobic theory could be applied for the interpretation of results. The behavior of the residuals turned out to be dependent on the co-solvent fraction and the age of the oil spill. The values of K vary between 900 (l kg(-1)) and 2,900 (l kg(-1)) showing a general and marked increase for residues of increasing age. The determined parameters are useful for the modeling of environmental impact on polluted soils.

  18. Optimization of the protein concentration process from residual peanut oil-cake

    Directory of Open Access Journals (Sweden)

    Gayol, M. F.

    2013-12-01

    Full Text Available The objective of this study was to find the best process conditions for preparing protein concentrate from residual peanut oil-cake (POC. The study was carried out on POC from industrial peanut oil extraction. Different protein extraction and precipitation conditions were used: water/ flour ratio (10:1, 20:1 and 30:1, pH (8, 9 and 10, NaCl concentration (0 and 0.5 M, extraction time (30, 60 and 120 min, temperature (25, 40 and 60 °C, extraction stages (1, 2 and 3, and precipitation pH (4, 4.5 and 5. The extraction and precipitation conditions which showed the highest protein yield were 10:1 water/flour ratio, extraction at pH 9, no NaCl, 2 extraction stages of 30 min at 40 °C and precipitation at pH 4.5. Under these conditions, the peanut protein concentrate (PC contained 86.22% protein, while the initial POC had 38.04% . POC is an alternative source of protein that can be used for human consumption or animal nutrition. Therefore, it adds value to an industry residue.El objetivo de este trabajo fue encontrar las mejores condiciones para obtener un concentrado de proteínas a partir de la torta residual de maní (POC. El estudio se llevó a cabo en POC provenientes de la extracción industrial de aceite de maní. Se utilizaron distintas condiciones para la extracción y precipitación de proteínas: relación agua / harina (10:1, 20:1 y 30:1, pH de extracción (8, 9 y 10, concentración de NaCl (0 y 0,5 M, tiempo de extracción (30, 60 y 120 min, temperatura (25, 40 y 60 °C, número de etapas de extracción (1, 2 y 3, y el pH de precipitación (4, 4,5 y 5. Las condiciones de extracción y de precipitación que mostraron mayor rendimiento de proteína fueron: relación de 10:1 en agua / harina, pH de extracción de 9, en ausencia de NaCl, 2 etapas de extracción de 30 min cada una a 40 °C y el pH de precipitación de 4,5. En estas condiciones, el concentrado de proteína de maní (PC fue de 86,22%, mientras que el porcentaje de proteínas de

  19. 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

  20. Crucial role of mechanisms and modes of toxic action for understanding tissue residue toxicity and internal effect concentrations of organic chemicals

    NARCIS (Netherlands)

    Escher, B.I.; Ashauer, R.; Dyer, S.; Hermens, J.L.M.; van der Lee, J.H.; Leslie, H.A.; Mayer, P.; Meador, J.P.; Warne, M.S.J.

    2011-01-01

    This article reviews the mechanistic basis of the tissue residue approach for toxicity assessment (TRA). The tissue residue approach implies that whole-body or organ concentrations (residues) are a better dose metric for describing toxicity to aquatic organisms than is the aqueous concentration

  1. Evaluation of Postmortem Drug Concentrations in Bile Compared with Blood and Urine in Forensic Autopsy Cases.

    Science.gov (United States)

    Tominaga, Mariko; Michiue, Tomomi; Oritani, Shigeki; Ishikawa, Takaki; Maeda, Hitoshi

    2016-06-01

    For drug screening and pharmaco-/toxicokinetic analysis, bile as a major drug excretion route in addition to urine may be used in forensic autopsy cases; however, there are limited published data on correlations between bile and blood or urine drug concentrations. The present study retrospectively investigated drug concentrations in bile, compared with blood and urine concentrations, reviewing forensic autopsy cases during 6 years (January 2009-December 2014). Drugs were analyzed using automated gas chromatography-mass spectrometry following solid-liquid phase extraction. Compared with peripheral blood concentrations, bile concentrations were higher for most drugs; however, caffeine concentrations were similar. Bile concentrations were mostly lower than urine concentrations for amphetamines, caffeine and methylephedrine, but were usually similar to or higher for other drugs. Significant correlations were detected between bile and peripheral blood concentrations for amphetamines, several cold remedies, phenobarbital, phenothiazine derivatives and diazepam, as well as between bile and urine concentrations for amphetamines, caffeine, diphenhydramine, phenobarbital and promethazine derivatives. These findings suggest that bile can provide supplemental data useful in routine forensic toxicology, for the spectrum of drugs mentioned above, as well as for investigating pharmaco-/toxicokinetics and postmortem redistribution when analyzed in combination with drug concentrations at other sites. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. Evolution of residual-Zn available concentrations of Zn-EDTA chelate in two different soils.

    Science.gov (United States)

    Almendros, P.; Gonzalez, D.; Alvarez, J. M.

    2012-04-01

    Zinc chelates, such as Zn-EDTA have been widely used to correct deficiencies in this micronutrient in different crops. Several authors have suggested applying complexed forms of Zn to soils in order to offer an effective source of Zn to plants. When inorganic Zn sources are added to soils, the availability of Zn to plants tends to decrease with time. This is due to the aging of the metal or the transformation of the Zn that is normally available to plants into various less available forms. Soil properties are believed to influence the fixation and/or precipitation of added Zn. The objective of this study was to determine the changes over time in the concentrations of available residual-Zn in two different soils to which the Zn-EDTA chelate was applied. An experiment was conducted under controlled laboratory conditions in two different soils: an acidic soil [Typic Haploxeralf; field capacity, 6.65 g H2O/100 g soil; pHw (1/2.5, w/v), 6.2; texture USDA, sandy loam, with illite as the predominant clay; oxidizable organic carbon 0.29%; extractable P, 19.9 mg/kg] and a calcareous soil [Typic Calcixerept; field capacity, 20.5 g H2O/100 g soil; pHw (1/2.5, w/v), 8.2; texture USDA, loamy sand, with smectite as the predominant clay; oxidizable organic carbon 0.75%; extractable P, 12.6 mg/kg]. These soils were treated with a synthetic chelate, Zn-ethylenediaminetetraacetate (Zn-EDTA), at different rates of application [0 (nil-Zn), 5 and 10 mg Zn kg-1 soil]. The potential available Zn concentrations were estimated at four experimental times (0, 15, 45 and 75 d) by the Mehlich-3 and DTPA-AB extraction methods. The results obtained showed the evolution of available Zn over experimental time, for each treatment. The Zn concentrations in both soils showed significant differences over experimental time. Zn-EDTA applied at both Zn rates (5 and 10 mg Zn kg-1) was associated with high variations in available Zn concentrations. However, in both soils, the decreases in available Zn

  3. Qualitative and Quantitative Drug residue analyses: Florfenicol in white-tailed deer (Odocoileus virginianus) and supermarket meat by liquid chromatography tandem-mass spectrometry.

    Science.gov (United States)

    Anderson, Shanoy C; Subbiah, Seenivasan; Gentles, Angella; Austin, Galen; Stonum, Paul; Brooks, Tiffanie A; Brooks, Chance; Smith, Ernest E

    2016-10-15

    A method for confirmation and detection of Florfenicol amine residues in white-tailed deer tissues was developed and validated in our laboratory. Tissue samples were extracted with ethyl acetate and cleaned up on sorbent (Chem-elut) cartridges. Liguid chromatography (LC) separation was achieved on a Zorbax Eclipse plus C18 column with gradient elution using a mobile phase composed of ammonium acetate in water and methanol at a flow rate of 300μL/min. Qualitative and quantitative analyses were carried out using liquid chromatography - heated electrospray ionization(HESI) and atmospheric pressure chemical ionization (APCI)-tandem mass spectrometry in the multiple reaction monitoring (MRM) interface. The limits of detection (LODs) for HESI and APCI probe were 1.8ng/g and 1.4ng/g respectively. Limits of quantitation (LOQs) for HESI and APCI probe were 5.8ng/g and 3.4ng/g respectively. Mean recovery values ranged from 79% to 111% for APCI and 30% to 60% for HESI. The validated method was used to determine white-tailed deer florfenicol tissue residue concentration 10-days after exposure. Florfenicol tissue residues concentration ranged from 0.4 to 0.6μg/g for liver and 0.02-0.05μg/g for muscle and a trace in blood samples. The concentration found in the tested edible tissues were lower than the maximum residual limit (MRL) values established by the federal drug administration (FDA) for bovine tissues. In summary, the resulting optimization procedures using the sensitivity of HESI and APCI probes in the determination of florfenicol in white-tailed deer tissue are the most compelling conclusions in this study, to the extent that we have applied this method in the evaluation of supermarket samples drug residue levels as a proof of principle. Copyright © 2016. Published by Elsevier B.V.

  4. Analysis of veterinary drug residue monitoring results for commercial livestock products in Taiwan between 2011 and 2015.

    Science.gov (United States)

    Lee, Hsin-Chun; Chen, Chi-Min; Wei, Jen-Ting; Chiu, Hsiu-Yi

    2018-04-01

    Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and eggs from food-producing animals, governments and relevant agencies established laws and regulations for the use of veterinary drugs. It is, therefore, necessary to monitor the content of residual drugs in livestock products at regular intervals to assess whether the regulations have resulted in the effective management of food product safety, and to prevent and manage sudden problems related to this issue. A 2011-2015 livestock product post-marketing monitoring program launched by the Taiwan Food and Drug Administration (TFDA) inspected 1487 livestock products. Over the past 5 years, there were 34 samples identified that did not conform to the regulations; these samples included residue drugs such as β-agonists, chloramphenicols, β-lactam antibiotics, sulfa drugs, enrofloxacin, and lincomycin. Inspections of commercial livestock products with the consistent cooperation of agricultural authorities did not detect the drugs that were banned by the government, whereas the detection of other drugs decreased annually with an increase in the post-market monitoring sample size. In the future, the TFDA will continue to monitor the status of residual veterinary drugs in commercial livestock products, adjust the sampling of food products annually according to monitoring results, and closely cooperate with agricultural authorities on source management. Copyright © 2017. Published by Elsevier B.V.

  5. Immunology-Based Techniques for the Detection of Veterinary Drug Residues in Foods

    Science.gov (United States)

    Reig, Milagro; Toldrá, Fidel

    Veterinary drugs are used in farm animals, via the feed or the drinking water, to prevent the outbreak of diseases or even for the treatment of diseases. However, the growth of animals may be promoted through the use of hormones and antibiotics. Depending on the type of residue and the application and washing conditions, these substances or its metabolites may remain in meat and other foods of animal origin and may cause adverse effects on consumers’ health. This is the main reason why its use is strictly regulated or even banned (case of the European Union) in different countries. Antibiotics typically used for growth promotion include chloramphenicol, nitrofurans, and enrofloxacin but others like sulphonamides, macrolides etc. may also be used (Reig & Toldrá, 2007).

  6. Influence of Bleaching on Flavor of 34% Whey Protein Concentrate and Residual Benzoic Acid Concentration in Dried Whey Proteins

    Science.gov (United States)

    Previous studies have shown that bleaching negatively affects the flavor of 70% whey protein concentrate (WPC70), but bleaching effects on lower-protein products have not been established. Benzoyl peroxide (BP), a whey bleaching agent, degrades to benzoic acid (BA) and may elevate BA concentrations...

  7. Influence of bleaching on flavor of 34% whey protein concentrate and residual benzoic acid concentration in dried whey products

    Science.gov (United States)

    Previous studies have shown that bleaching negatively affects the flavor of 70% whey protein concentrate (WPC70), but bleaching effects on lower-protein products have not been established. Benzoyl peroxide (BP), a whey bleaching agent, degrades to benzoic acid (BA) and may elevate BA concentrations...

  8. Predicting Drug Concentration-Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically-Based Pharmacokinetic Model

    NARCIS (Netherlands)

    Yamamoto, Yumi; Välitalo, Pyry A; Huntjens, Dymphy R; Proost, Johannes H; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W; van den Berg, Dirk-Jan; Hartman, Robin; Wong, Yin Cheong; Danhof, Meindert; van Hasselt, John G C; de Lange, Elizabeth C M

    2017-01-01

    Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction of drug concentrations in physiologically relevant CNS

  9. Residual antibiofilm effects of various concentrations of double antibiotic paste used during regenerative endodontics after different application times.

    Science.gov (United States)

    Jenks, Daniel B; Ehrlich, Ygal; Spolnik, Kenneth; Gregory, Richard L; Yassen, Ghaeth H

    2016-10-01

    We investigated the residual antibiofilm effects of different concentrations of double antibiotic paste (DAP) applied on radicular dentin for 1 or 4 weeks. Dentin samples were prepared (n=120), sterilized and pretreated for 1 or 4 weeks with the clinically used concentration of DAP (500mg/mL), low concentrations of DAP (1, 5 or 50mg/mL) loaded into a methylcellulose system, calcium hydroxide (Ca(OH) 2 ), or placebo paste. After the assigned treatment time, treatment pastes were rinsed off and the samples were kept independently in phosphate buffered saline for 3 weeks. Pretreated dentin samples were then inoculated with Enterococcus faecalis and bacterial biofilms were allowed to grow for an additional 3 weeks. Biofilms were then retrieved from dentin using biofilm disruption assays, diluted, spiral plated, and quantified. Fisher's Exact and Wilcoxon rank sum tests were used for statistical comparisons (α=0.05). Dentin pretreatment for 4 weeks with 5, 50 or 500mg/mL of DAP demonstrated significantly higher residual antibiofilm effects and complete eradication of E. faecalis biofilms in comparison to a 1 week pretreatment with similar concentrations. However, dentin pretreated with 1mg/mL of DAP or Ca(OH) 2 did not provide a substantial residual antibiofilm effect regardless of the application time. Dentin pretreatment with 5mg/mL of DAP or higher for 4 weeks induced significantly higher residual antibiofilm effects in comparison to a 1 week pretreatment with the same concentrations. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. A survey of chlortetracycline concentration in feed and its residue in chicken egg in commercial layer farms.

    Science.gov (United States)

    Kodimalar, K; Rajini, R A; Ezhilvalavan, S; Sarathchandra, G

    2014-06-01

    The worldwide increase in the use of antibiotics as an integral part of poultry and livestock production industry has recently received increasing attention as a contributory factor in the international emergence of antibiotic-resistant bacteria in human beings. To gauge the presence of the aforementioned scenario in the Indian context, a preliminary survey was conducted to assess the use of chlortetracycline (CTC) in 12 commercial layer farms and to quantify and confirm its residue in the egg. Samples of feed and eggs were collected at day 0 (prior to CTC addition), 3rd, 5th and 7th day during treatment and on the 9th and 14th day (2nd and 7th day after withdrawal of CTC) from each of the 12 commercial poultry farms studied. Concentration of CTC in feed was significantly (P less than 0.01) high on the 3rd, 5th and 7th day. On the 9th day and 14th day CTC concentration in feed was significantly (P less than 0.01) lower compared to the earlier 3 days studied. A highly significant difference (P less than 0.01) of the antibiotic residue in egg was observed in all the 5 days with high residual levels of CTC in egg. CTC in feed and its residue in egg were detected even on the 9th and 14th day respectively.

  11. 75 FR 48928 - Codex Alimentarius Commission: Meeting of the Codex Committee on Residues of Veterinary Drugs in...

    Science.gov (United States)

    2010-08-12

    ....hhs.gov For further information about the public meeting, contact: Ken Lowery, ] International Issues... determination of veterinary drug residues in foods. The Committee is hosted by the United States. Issues To Be... all its programs and activities on the basis of race, color, national origin, gender, religion, age...

  12. Analytical strategies for residue analysis of veterinary drugs and growth-promoting agents in food-producing animals - A review

    NARCIS (Netherlands)

    Stolker, A.A.M.; Brinkman, U.A.T.

    2005-01-01

    After a brief introduction into the field of veterinary drugs and growth-promoting agents, the most important EU regulations and directives for the inspection of food-producing animals and animal products regarding the residue control of these substances are presented and discussed. Main attention

  13. Impact of active metabolites on monitoring plasma concentrations of therapeutic drugs.

    Science.gov (United States)

    Atkinson, A J; Stec, G P; Lertora, J J; Ruo, T I; Thenot, J P

    1980-01-01

    Monitoring plasma concentrations of therapeutic drugs presents special problems when these drugs are metabolized to compounds that have pharmacologic activity. This presentation reviews several methods for evaluating the pharmacologic activity of drug metabolites and describes the impact of active drug metabolites on the pharmacokinetic design of dose regimens and on the formulation of guidelines for plasma level interpretation. Lidocaine and monoethylglycinexylidide illustrate the considerations that pertain when both a drug and its active metabolite have similar therapeutic and toxic actions. Procainamide and N-acetylprocainamide exemplify the much more complex situation that arises when a drug and its active metabolite have different pharmacologic activity.

  14. EVALUATION OF FERRIC CHLORIDE AND ALUM EFFICIENCIES IN ENHANCED COAGULATION FOR TOC REMOVAL AND RELATED RESIDUAL METAL CONCENTRATIONS

    Directory of Open Access Journals (Sweden)

    A. Mesdaghinia, M. T. Rafiee, F. Vaezi and A. H. Mahvi

    2005-07-01

    Full Text Available Although the removal of colloidal particles continues to be an important reason for using coagulation, a newer objective, the removal of natural organic matter (NOM to reduce the formation of disinfection by-products (DBPs, is growing in importance. Enhanced coagulation is thus introduced to most water utilities treating surface water. Bench-scale experiments were conducted to compare the effectiveness of alum and ferric chloride in removing DBPs precursors from eight synthetic water samples, each representing a different element of the USEPA’s 3×3 enhanced coagulation matrix. The effect of enhanced coagulation on the residual metal (aluminum/iron concentration in the treated water was assessed as well. The removal of total organic carbon (TOC was dependent on the coagulant type and was enhanced with increasing coagulant dose, but the latter had no further considerable effect in case of increasing to high levels. For all the treated samples coagulation with ferric chloride proved to be more effective than alum at similar doses and the mean values of treatment efficiencies were 51% and 32% for ferric chloride and alum, respectively. Ferric chloride was therefore considered the better chemical for enhancing the coagulation process. Besides, due to less production of sludge by this coagulant, it would be predicted that treatment plants would be confronted to fewer problems with respect to final sludge disposal. Measurements of residual metal in treated water indicated that iron and aluminum concentrations had been increased as expected but the quality of water concerning the residual metal deteriorated much more in cases of under-dosing. Despite expecting high residual Al and Fe concentrations under enhanced coagulation, metal concentrations were frequently remained low and were not increased appreciably.

  15. Analysis of pesticide and veterinary drug residues in baby food by liquid chromatography coupled to Orbitrap high resolution mass spectrometry.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Romero-González, Roberto; Luis Martínez, Vidal José; Garrido Frenich, Antonia

    2015-01-01

    Pesticide and veterinary drug residues have been simultaneously determined in several baby foods as meat, fish and vegetable-based baby food. A generic extraction method without clean-up step was applied. Moreover, the use of a representative matrix for proper quantification of all target compounds was studied and the best results were obtained when vegetable-based baby food was used as representative matrix, allowing the reliable quantification of more than 300 compounds. The method was validated and good recoveries were obtained for most of compounds at concentrations higher than 50 µg kg(-1). Limits of detection (LOD) ranged from 0.5 to 50 µg kg(-1), whereas limits of quantification (LOQ) were established between 10 and 100 µg kg(-1). Limits of identification (LOIs) ranged from 0.5 to 50 µg kg(-1). This method was applied to the analysis of 46 different baby food samples and no positive samples were found. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Importance of Drug Concentrations and Nutritional Status During ...

    African Journals Online (AJOL)

    The concentrations of CQ and sulfadoxine (S) were determined by HPLC in 100μl of capillary blood on filter paper. Multiple logistic regressions were used to determine associations with outcomes. Stunting (height-for-age <-2 Z-scores) was more common (27.7%) compared to underweight (wt-for-age <-2 Z-scores, 19.3%) ...

  17. Determination of pesticides and veterinary drug residues in food by liquid chromatography-mass spectrometry: A review.

    Science.gov (United States)

    Masiá, Ana; Suarez-Varela, Maria Morales; Llopis-Gonzalez, Agustin; Picó, Yolanda

    2016-09-14

    Monitoring of pesticides and veterinary drug residues is required to enforce legislation and guarantee food safety. Liquid chromatography-mass spectrometry (LC-MS) is the prevailing technique for assessing both types of residues because LC offers a versatile and universal separation mechanism suitable for non-gas chromatography (GC) amenable and the majority of GC-amenable compounds. This characteristic becomes more relevant when LC is coupled to MS because the high sensitivity and specificity of the detector allows to apply generic sample preparation procedures, which simultaneously extract a wide variety of residues with different physico-chemical properties. Determination of metabolites and degradation products, non-target suspected screening of an increasing number of residues, and even unknowns identification are also becoming inherent LC-MS advantages thanks to the latest advances. For routine analysis and, in particular, for official surveillance purposes in food control, analytical methods properly validated following strict guidelines are needed. After a brief introduction and an outline of the legislation applicable around the world, aspects such as improvement of specificity of high-throughput methods, resolution and mass accuracy of identification strategies and quantitative accuracy are critically reviewed in this article. In them, extraction, separation and determination are emphasized. The main objective is to offer an assessment of the state of the art and identify research needs and future trends in determining pesticide and veterinary drug residues in food by LC-MS. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. High variation subarctic topsoil pollutant concentration prediction using neural network residual kriging

    Science.gov (United States)

    Sergeev, A. P.; Tarasov, D. A.; Buevich, A. G.; Subbotina, I. E.; Shichkin, A. V.; Sergeeva, M. V.; Lvova, O. A.

    2017-06-01

    The work deals with the application of neural networks residual kriging (NNRK) to the spatial prediction of the abnormally distributed soil pollutant (Cr). It is known that combination of geostatistical interpolation approaches (kriging) and neural networks leads to significantly better prediction accuracy and productivity. Generalized regression neural networks and multilayer perceptrons are classes of neural networks widely used for the continuous function mapping. Each network has its own pros and cons; however both demonstrated fast training and good mapping possibilities. In the work, we examined and compared two combined techniques: generalized regression neural network residual kriging (GRNNRK) and multilayer perceptron residual kriging (MLPRK). The case study is based on the real data sets on surface contamination by chromium at a particular location of the subarctic Novy Urengoy, Russia, obtained during the previously conducted screening. The proposed models have been built, implemented and validated using ArcGIS and MATLAB environments. The networks structures have been chosen during a computer simulation based on the minimization of the RMSE. MLRPK showed the best predictive accuracy comparing to the geostatistical approach (kriging) and even to GRNNRK.

  19. Uncertainty assessment of gamma-aminobutyric acid concentration of different brain regions in individual and group using residual bootstrap analysis.

    Science.gov (United States)

    Chen, Meng; Liao, Congyu; Chen, Song; Ding, Qiuping; Zhu, Darong; Liu, Hui; Yan, Xu; Zhong, Jianhui

    2017-06-01

    The aim of this work is to quantify individual and regional differences in the relative concentration of gamma-aminobutyric acid (GABA) in human brain with in vivo magnetic resonance spectroscopy. Spectral editing Mescher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence and GABA analysis toolkit (Gannet) were used to detect and quantify GABA in anterior cingulate cortex (ACC) and occipital cortex (OCC) of healthy volunteers. Residual bootstrap, a model-based statistical analysis technique, was applied to resample the fitting residuals of GABA from the Gaussian fitting model (referred to as GABA + thereafter) in both individual and group data of ACC and OCC. The inter-subject coefficient of variation (CV) of GABA + in OCC (20.66 %) and ACC (12.55 %) with residual bootstrap was lower than that of a standard Gaussian model analysis (21.58 % and 16.73 % for OCC and ACC, respectively). The intra-subject uncertainty and CV of OCC were lower than that of ACC in both analyses. The residual bootstrap analysis thus provides a more robust uncertainty estimation of individual and group GABA + detection in different brain regions, which may be useful in our understanding of GABA biochemistry in brain and its use for the diagnosis of related neuropsychiatric diseases.

  20. Short communication: Drug residues in goat milk after prophylactic use of antibiotics in intravaginal sponges for estrus synchronization.

    Science.gov (United States)

    Romero, T; Balado, J; Althaus, R L; Beltrán, M C; Molina, M P

    2016-01-01

    The aim of this study was to determine whether the prophylactic use of antibiotics in intravaginal sponges used for estrus synchronization in goats may result in the presence of inhibitors in milk and, therefore, of positive results by microbial screening tests. Ninety-eight Murciano-Granadina goats were used, divided into 7 groups of 14 animals. Intravaginal sponges were placed in 6 groups using 2 concentrations of 3 different antibiotics: doxycycline, oxytetracycline, and sulfathiazole-framycetin. The sponges of the control group were placed without antibiotics. Milk samples were collected daily until 7 d posttreatment and analyzed using 3 microbial tests. Positive samples were retested by specific receptor-binding assays to confirm the positive results. Vaginal status was evaluated by visual assessment of the external aspect of the sponges after removal. The microbial test response was not affected by either day posttreatment or dose of antibiotic used, except for oxytetracycline at the higher concentration. Moreover, no positive results were obtained using receptor-binding assays, suggesting that residues, if present in milk, did not exceed the regulatory (safety) levels established for these drugs. The occurrence of soiled sponges was higher in the control group. With respect to the dose of antibiotics used, no significant differences were found for the lower dose administered. However, a significant increase in the percentage of clean sponges was observed for the higher dose of doxycycline. We conclude that the prophylactic use of low doses of doxycycline, oxytetracycline, or sulfathiazole in intravaginal sponges used for synchronization of estrus helps to reduce clinical vaginitis in dairy goats and does not seem to be the cause of positive results in microbial inhibitor tests used to detect antibiotics in goat milk. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  1. 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.

  2. A direct qPCR method for residual DNA quantification in monoclonal antibody drugs produced in CHO cells.

    Science.gov (United States)

    Hussain, Musaddeq

    2015-11-10

    Chinese hamster ovary (CHO) cells are the host cell of choice for manufacturing of monoclonal antibody (mAb) drugs in the biopharmaceutical industry. Host cell DNA is an impurity of such manufacturing process and must be controlled and monitored in order to ensure drug purity and safety. A conventional method for quantification of host residual DNA in drug requires extraction of DNA from the mAb drug substance with subsequent quantification of the extracted DNA using real-time PCR (qPCR). Here we report a method where the DNA extraction step is eliminated prior to qPCR. In this method, which we have named 'direct resDNA qPCR', the mAb drug substance is digested with a protease called KAPA in a 96-well PCR plate, the protease in the digest is then denatured at high temperature, qPCR reagents are added to the resultant reaction wells in the plate along with standards and controls in other wells of the same plate, and the plate subjected to qPCR for analysis of residual host DNA in the samples. This direct resDNA qPCR method for CHO is sensitive to 5.0fg of DNA with high precision and accuracy and has a wide linear range of determination. The method has been successfully tested with four mAbs drug, two IgG1 and two IgG4. Both the purified drug substance as well as a number of process intermediate samples, e.g., bioreactor harvest, Protein A column eluate and ion-exchange column eluates were tested. This method simplifies the residual DNA quantification protocol, reduces time of analysis and leads to increased assay sensitivity and development of automated high-throughput methods. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Non-irritant concentrations and amounts of active ingredient in drug patch tests.

    Science.gov (United States)

    Brajon, Delphine; Menetre, Sophie; Waton, Julie; Poreaux, Claire; Barbaud, Annick

    2014-09-01

    Drug patch tests (DPTs) with medicaments suspected of causing an allergic reaction represent a method of diagnostic testing that is low risk; DPTs can reproduce delayed hypersensitivity to drugs, and entail only a moderate re-exposure of patients to potential offending drugs. We assessed the non-irritating concentrations of DPTs and determined the amounts of active ingredient (AI) contained in the drugs used in the tests. The objectives were to assess the non-irritating concentration of DPTs and determine the amounts of active ingredient (AI) contained in the drugs used in the tests. From a retrospective, single-centre study of all patients investigated during a 6-year period with a drug eruption, each potentially responsible drug was tested with the commercially available preparation diluted to 30% in water, petrolatum, or alcohol. Data collection was performed with a customized computer database. For each type of DPT studied, the numbers of positive and negative test results were recorded. The amount of AI contained in the DPT (as a percentage) was then calculated after weighing of each tablet. Of the 5558 DPTs studied, all were non-irritant. The average concentration of AI was 9.8%; 25% of DPTs had an AI concentration of concentration of > 16%. The AI concentration ranged from 0.05% (digoxin) to 30% (paracetamol lyophilisate). These data provide thresholds for the non-irritating concentration of AI of 68 different drugs, and thresholds for the non-irritating dilution for 82 drugs, and will help to standardize DPT methods. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    OpenAIRE

    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.

    2017-01-01

    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), m...

  5. 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....

  6. Multi-residue method for the detection of veterinary drugs in distillers grains by liquid chromatography-Orbitrap high resolution mass spectrometry.

    Science.gov (United States)

    Kaklamanos, George; Vincent, Ursula; von Holst, Christoph

    2013-12-27

    Distillers Grain (DG) is an important by-product of ethanol production. The ethanol production process uses only the starch portion of the plant and all the remaining nutrients, protein, fat, minerals, and vitamins remain in DGs, a valuable feed material for livestock. The use of antimicrobial drugs is helpful to limit harmful bacterial growth during the early part of the fermentation process. This can lead to the possible presence of contaminants in the by-products that are used in the food and feed industries, resulting in a major concern for the development of bacterial resistance in both humans and animals. To facilitate the detection of antimicrobial and other commonly used veterinary drugs in DGs, a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method was developed targeting a wide range of 12 chemical classes of anti-bacterial substances and drugs, such as ionophore and non-ionophore authorized coccidiostats, banned coccidiostats, macrolides, tetracyclines, nitroimidazoles, amphenicols, quinolones, sulphonamides, tranquilizers, non-steroidal anti-inflammatory drugs and benzimidazoles. Following a simple and fast extraction step with a mixture of organic solvents, the extract was directly injected into the LC coupled to an Orbitrap mass analyzer. The identification of residues is based on accurate mass measurement. The high mass resolution of 50,000 full width at half maximum (FWHM) and corresponding narrow mass windows permitted a very selective and sensitive detection of the analytes in such a complex matrix. A single-laboratory validation procedure was carried out evaluating selectivity, sensitivity, linearity, precision and accuracy. The method showed satisfactory analytical performance for precision and trueness, and allowed the determination of the compounds at low concentration. The proposed multi-method demonstrated that liquid chromatography coupled to an Orbitrap mass spectrometer is a promising analytical technique, suitable for

  7. Determination of pesticides and veterinary drug residues in food by liquid chromatography-mass spectrometry: A review

    Energy Technology Data Exchange (ETDEWEB)

    Masiá, Ana [Food and Environmental Safety Research Group, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); Research Center on Desertification (CIDE, UV-CSIC-GV), Carretera Moncada-Náquera, Moncada (Spain); Suarez-Varela, Maria Morales; Llopis-Gonzalez, Agustin [Unit of Public Health, Hygiene and Environmental Health, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid (Spain); Center for Advanced Research in Public Health (CSISP-FISABIO), Valencia (Spain); Picó, Yolanda, E-mail: Yolanda.Pico@uv.es [Food and Environmental Safety Research Group, Department of Preventive Medicine and Public Health, Food Science, Toxicology and Legal Medicine, University of Valencia, Valencia (Spain); Research Center on Desertification (CIDE, UV-CSIC-GV), Carretera Moncada-Náquera, Moncada (Spain); CIBER Epidemiología y Salud Pública (CIBERESP), Madrid (Spain)

    2016-09-14

    Monitoring of pesticides and veterinary drug residues is required to enforce legislation and guarantee food safety. Liquid chromatography-mass spectrometry (LC-MS) is the prevailing technique for assessing both types of residues because LC offers a versatile and universal separation mechanism suitable for non-gas chromatography (GC) amenable and the majority of GC-amenable compounds. This characteristic becomes more relevant when LC is coupled to MS because the high sensitivity and specificity of the detector allows to apply generic sample preparation procedures, which simultaneously extract a wide variety of residues with different physico-chemical properties. Determination of metabolites and degradation products, non-target suspected screening of an increasing number of residues, and even unknowns identification are also becoming inherent LC-MS advantages thanks to the latest advances. For routine analysis and, in particular, for official surveillance purposes in food control, analytical methods properly validated following strict guidelines are needed. After a brief introduction and an outline of the legislation applicable around the world, aspects such as improvement of specificity of high-throughput methods, resolution and mass accuracy of identification strategies and quantitative accuracy are critically reviewed in this article. In them, extraction, separation and determination are emphasized. The main objective is to offer an assessment of the state of the art and identify research needs and future trends in determining pesticide and veterinary drug residues in food by LC-MS. - Highlights: • An overview of status and future trends in this field. • Analytical method's compliance with guidelines to ensure reliability. • QuEChERS platform is a referent to extract both, pesticides and veterinary drugs in food. • The progress that liquid chromatography has shown in recent years is revised. • Determination of target, non-target and unknowns is

  8. Determination of pesticides and veterinary drug residues in food by liquid chromatography-mass spectrometry: A review

    International Nuclear Information System (INIS)

    Masiá, Ana; Suarez-Varela, Maria Morales; Llopis-Gonzalez, Agustin; Picó, Yolanda

    2016-01-01

    Monitoring of pesticides and veterinary drug residues is required to enforce legislation and guarantee food safety. Liquid chromatography-mass spectrometry (LC-MS) is the prevailing technique for assessing both types of residues because LC offers a versatile and universal separation mechanism suitable for non-gas chromatography (GC) amenable and the majority of GC-amenable compounds. This characteristic becomes more relevant when LC is coupled to MS because the high sensitivity and specificity of the detector allows to apply generic sample preparation procedures, which simultaneously extract a wide variety of residues with different physico-chemical properties. Determination of metabolites and degradation products, non-target suspected screening of an increasing number of residues, and even unknowns identification are also becoming inherent LC-MS advantages thanks to the latest advances. For routine analysis and, in particular, for official surveillance purposes in food control, analytical methods properly validated following strict guidelines are needed. After a brief introduction and an outline of the legislation applicable around the world, aspects such as improvement of specificity of high-throughput methods, resolution and mass accuracy of identification strategies and quantitative accuracy are critically reviewed in this article. In them, extraction, separation and determination are emphasized. The main objective is to offer an assessment of the state of the art and identify research needs and future trends in determining pesticide and veterinary drug residues in food by LC-MS. - Highlights: • An overview of status and future trends in this field. • Analytical method's compliance with guidelines to ensure reliability. • QuEChERS platform is a referent to extract both, pesticides and veterinary drugs in food. • The progress that liquid chromatography has shown in recent years is revised. • Determination of target, non-target and unknowns is

  9. Screening of veterinary drug residues in milk from individual farms in Macedonia

    Directory of Open Access Journals (Sweden)

    Dimitrieska-Stojkovic Elizabeta

    2011-05-01

    Full Text Available A total of 497 raw milk samples collected at individual farms and collection tanks for milk from eight regions from Macedonia were examined for chloramphenicol, sulfonamides, quinolones and tetracyclines from October 2008 until April 2011. Immunoassay methods were used for the determination of chloramphenicol, sulfonamides and quinolones, and high performance liquid chromatography with Diode Array detection was applied for screening of tetracyclines. The methods were validated according to the recommendations laid down by European Commission Decision 2002/657/EC. The obtained data confirmed that the methods were appropriate for detection of antibiotics determined, at the concentration level of interest. Measured range of concentrations (in μg/kg was 13.5-147.9 for sulfonamides, 0.6-22.0 for quinolones and 17.4-149.1 for tetracyclines, with calculated mean values (in μg/kg 24.7 for sulfonamides, 12.6 for qinolones and 41.9 for tetracyclines. None of the analyzed samples showed presence of chloramphenicol over the minimum required performance level value of the screening method. The calculated estimated daily intakes for the average daily consumption of 200 mL of milk for an adult in Macedonia, for the examined antimicrobials, obtained levels 2 to 100 times lower than the values of the acceptable daily intakes fixed by World Health Organization. This indicates that toxicological risk associated with the consumption of analyzed milk could not be considered as a public health issue with regards to these veterinary drugs.

  10. Real-time amplification of HLA-DQA1 for counting residual white blood cells in filtered platelet concentrates.

    Science.gov (United States)

    Mohammadi, Tamimount; Reesink, Henk W; Vandenbroucke-Grauls, Christina M J E; Savelkoul, Paul H M

    2004-09-01

    BACKGROUND A real-time polymerase chain reaction (PCR) assay based on amplification of a conserved region of the HLA-DQA1 locus was developed and validated to assess its suitability in quantitating low levels of white blood cells (WBCs) in filtered platelet (PLT) concentrates (PCs). To determine the detection limit, serial dilutions of nonfiltered PCs with known quantities of WBCs were prepared. The analytical sensitivity and accuracy of the assay was tested with WBC concentrations ranging from 300 to 0.03 per microL with real-time PCR and flow cytometry. In addition, 126 random PCs were investigated to assess the capacity of the PCR method to quantify residual WBCs in clinical specimens. A sensitivity of 0.2 WBC equivalent per micro L (1.5 x 10(4) WBC equivalents/unit) was achieved. The assay was shown to be accurate and the HLA-DQA1 gene was reproducibly and consistently amplified in all tested samples (coefficient of variance of < 5%). Overall, the results of the PCR assay correlated well with those of the flow cytometry. The PCR assay detected a concentration of 3 WBCs per micro L (approximately 1 x 10(6) WBCs/unit) with 100 percent accuracy. Real-time PCR is rapid, sensitive, accurate, and reproducible. Hence this approach may prove suitable in routine monitoring of residual WBCs in PCs.

  11. High hole mobility p-type GaN with low residual hydrogen concentration prepared by pulsed sputtering

    Science.gov (United States)

    Arakawa, Yasuaki; Ueno, Kohei; Kobayashi, Atsushi; Ohta, Jitsuo; Fujioka, Hiroshi

    2016-08-01

    We have grown Mg-doped GaN films with low residual hydrogen concentration using a low-temperature pulsed sputtering deposition (PSD) process. The growth system is inherently hydrogen-free, allowing us to obtain high-purity Mg-doped GaN films with residual hydrogen concentrations below 5 × 1016 cm-3, which is the detection limit of secondary ion mass spectroscopy. In the Mg profile, no memory effect or serious dopant diffusion was detected. The as-deposited Mg-doped GaN films showed clear p-type conductivity at room temperature (RT) without thermal activation. The GaN film doped with a low concentration of Mg (7.9 × 1017 cm-3) deposited by PSD showed hole mobilities of 34 and 62 cm2 V-1 s-1 at RT and 175 K, respectively, which are as high as those of films grown by a state-of-the-art metal-organic chemical vapor deposition apparatus. These results indicate that PSD is a powerful tool for the fabrication of GaN-based vertical power devices.

  12. High hole mobility p-type GaN with low residual hydrogen concentration prepared by pulsed sputtering

    Directory of Open Access Journals (Sweden)

    Yasuaki Arakawa

    2016-08-01

    Full Text Available We have grown Mg-doped GaN films with low residual hydrogen concentration using a low-temperature pulsed sputtering deposition (PSD process. The growth system is inherently hydrogen-free, allowing us to obtain high-purity Mg-doped GaN films with residual hydrogen concentrations below 5 × 1016 cm−3, which is the detection limit of secondary ion mass spectroscopy. In the Mg profile, no memory effect or serious dopant diffusion was detected. The as-deposited Mg-doped GaN films showed clear p-type conductivity at room temperature (RT without thermal activation. The GaN film doped with a low concentration of Mg (7.9 × 1017 cm−3 deposited by PSD showed hole mobilities of 34 and 62 cm2 V−1 s−1 at RT and 175 K, respectively, which are as high as those of films grown by a state-of-the-art metal-organic chemical vapor deposition apparatus. These results indicate that PSD is a powerful tool for the fabrication of GaN-based vertical power devices.

  13. Sample-based reporting of official national control of veterinary drug residues

    DEFF Research Database (Denmark)

    Andersen, Jens Hinge; Jensen, Louise Grønhøj Hørbye; Madsen, Helle L.

    Data collection is an essential prerequisite for assessing compliance of chemical residues in food and for risk assessment. The present system for collecting aggregated data of residues of veterinary medicinal products and other substances in animals and animal products has limitations for risk...

  14. Electrochemical oxidation of drug residues in water by the example of tetracycline, gentamicin and Aspirin {sup trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Weichgrebe, D.; Danilova, E.; Rosenwinkel, K.H. [Inst. of Water Quality and Waste Management, Univ. of Hannover, Hannover (Germany); Vedenjapin, A.; Baturova, M. [Inst. of Organic Chemistry, Russian Academy of Science, Moscow (Russian Federation)

    2003-07-01

    The electrochemical oxidation as a method to destroy drug residues like Aspirin {sup trademark}, tetracycline or gentamicin in water was investigated with C-Anode (modified by manganese oxides) and Pt Anode. The mechanism of Aspirin {sup trademark} and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general the biological availability increases with progressive oxidation of the antibiotics. (orig.)

  15. Pentobarbital self-administration in rhesus monkeys: drug concentration and fixed-ratio size interactions.

    OpenAIRE

    Lemaire, G A; Meisch, R A

    1984-01-01

    Performances of three rhesus monkeys were reinforced by the oral delivery of pentobarbital and studied as functions of fixed-ratio size and drug concentration. Pentobarbital solutions and water were concurrently available on identical reinforcement schedules from separate liquid-delivery systems during 3-hour sessions. Under a fixed-ratio 16 schedule of drug availability, a descending series of drug concentrations was tested (4, 2, 1, 0.5, 0.25, 0.125, and 0.0625 mg/ml, followed by a retest a...

  16. Alkali solution extraction of rice residue protein isolates: Influence of alkali concentration on protein functional, structural properties and lysinoalanine formation.

    Science.gov (United States)

    Hou, Furong; Ding, Wenhui; Qu, Wenjuan; Oladejo, Ayobami Olayemi; Xiong, Feng; Zhang, Weiwei; He, Ronghai; Ma, Haile

    2017-03-01

    This study evaluated the nutrient property and safety of the rice residue protein isolates (RRPI) product (extracted by different alkali concentrations) by exploring the protein functional, structural properties and lysinoalanine (LAL) formation. The results showed that with the rising of alkali concentration from 0.03M to 0.15M, the solubility, emulsifying and foaming properties of RRPI increased at first and then descended. When the alkali concentration was greater than 0.03M, the RRPI surface hydrophobicity decreased and the content of thiol and disulfide bond, Lys and Cys significantly reduced. By the analysis of HPLC, the content of LAL rose up from 276.08 to 15,198.07mg/kg and decreased to 1340.98mg/kg crude protein when the alkali concentration increased from 0.03 to 0.09M and until to 0.15M. These results indicated that RRPI alkaline extraction concentration above 0.03M may cause severe nutrient or safety problems of protein. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A survey of chlortetracycline concentration in feed and its residue in ...

    Indian Academy of Sciences (India)

    Samples of feed and eggs were collected at day 0 (prior to CTC addition), 3rd, 5th and 7th day during treatment and on the 9th and 14th day (2nd and 7th day after withdrawal of CTC) from each of the 12 commercial poultry farms studied. Concentration of CTC in feed was significantly ( < 0.01) high on the 3rd, 5th and 7th ...

  18. 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.

  19. Characterizing chronic and acute health risks of residues of veterinary drugs in food: latest methodological developments by the joint FAO/WHO expert committee on food additives.

    Science.gov (United States)

    Boobis, Alan; Cerniglia, Carl; Chicoine, Alan; Fattori, Vittorio; Lipp, Markus; Reuss, Rainer; Verger, Philippe; Tritscher, Angelika

    2017-11-01

    The risk assessment of residues of veterinary drugs in food is a field that continues to evolve. The toxicological end-points to be considered are becoming more nuanced and in light of growing concern about the development of antimicrobial resistance, detailed analysis of the antimicrobial activity of the residues of veterinary drugs in food is increasingly incorporated in the assessment. In recent years, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has refined its approaches to provide a more comprehensive and fit-for-purpose risk assessment. This publication describes in detail the consideration of acute and chronic effects, the estimation of acute and chronic dietary exposure, current approaches for including microbiological endpoints in the risk assessment, and JECFA's considerations for the potential effects of food processing on residues from veterinary drugs. JECFA now applies these approaches in the development of health-based guidance values (i.e. safe exposure levels) for residues of veterinary drugs. JECFA, thus, comprehensively addresses acute and chronic risks by using corresponding estimates for acute and chronic exposure and suitable correction for the limited bioavailability of bound residues by the Gallo-Torres model. On a case-by-case basis, JECFA also considers degradation products that occur from normal food processing of food containing veterinary drug residues. These approaches will continue to be refined to ensure the most scientifically sound basis for the establishment of health-based guidance values for veterinary drug residues.

  20. 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.

  1. Zearalenone (ZEN) metabolism and residue concentrations in physiological specimens of dairy cows exposed long-term to ZEN-contaminated diets differing in concentrate feed proportions.

    Science.gov (United States)

    Dänicke, Sven; Keese, Christina; Meyer, Ulrich; Starke, Alexander; Kinoshita, Asako; Rehage, Jürgen

    2014-12-01

    A long-term feeding experiment with dairy cows was performed to investigate the effects of feeding a Fusarium toxin contaminated (FUS) and a background-contaminated control (CON) ration with a mean concentrate feed proportion of 50% during the first 11 weeks after parturition (Groups FUS-50, CON-50, Period 1), and with concentrate feed proportions of 30% or 60% during the remaining 17 weeks (Groups CON-30, CON-60, FUS-30 and FUS-60, Period 2), on zearalenone (ZEN) residue levels in blood serum, milk, urine and bile. ZEN, α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL), zearalanone (ZAL), α-zearalanol (α-ZAL) and β-zearalanol (β-ZAL) were determined by HPLC with fluorescence detection. The ZEN concentrations of the rations fed to Groups CON-50, FUS-50 (Period 1), CON-30, CON-60, FUS-30 and FUS-60 (Period 2) amounted to 53.1, 112.7, 35.0, 24.4, 73.8 and 72.5 µg/kg dry matter, respectively. The concentrations of ZEN, α-ZEL, β-ZEL, ZAN, α-ZAL and β-ZAL in serum, urine and milk were lower than 1, 1, 4, 100, 50 and 200 ng/g, respectively, while ZEN, α-ZEL and β-ZEL were detected in bile. Their levels changed with oral ZEN exposure in the course of the experiment and in a similar direction with concentrate feed proportion (Period 2 only). Thus the proportions of the individual β-ZEL, α-ZEL and ZEN concentrations of their sum varied only in narrow ranges of 68-76%, 6-13% and 12-20%, respectively. Interestingly, the bile concentrations of β-ZEL, α-ZEL and ZEN of Groups CON-60 and FUS-60 amounted to only approximately 50%, 45% and 62%, respectively, of those of Groups CON-30 and FUS-30 despite a similar or even lower ZEN exposure. The results indicate that conversion of ZEN to its detectable metabolites was not changed by different dietary concentrate feed proportions while their absolute levels were decreased. These findings might suggest concentrate feed proportion-dependent and rumen fermentation-mediated alterations in ZEN/metabolite degradation, and

  2. Evaluation of ground calcite/water heavy media cyclone suspensions for production of residual plastic concentrates.

    Science.gov (United States)

    Gent, Malcolm; Sierra, Héctor Muñiz; Menéndez, Mario; de Cos Juez, Francisco Javier

    2018-01-01

    Viable recycled residual plastic (RP) product(s) must be of sufficient quality to be reusable as a plastic or source of hydrocarbons or fuel. The varied composition and large volumes of such wastes usually requires a low cost, high through-put recycling method(s) to eliminate contaminants. Cyclone separation of plastics by density is proposed as a potential method of achieving separations of specific types of plastics. Three ground calcite separation medias of different grain size distributions were tested in a cylindrical cyclone to evaluate density separations at 1.09, 1.18 and 1.27 g/cm 3 . The differences in separation recoveries obtained with these medias by density offsets produced due to displacement of separation media solid particles within the cyclone caused by centrifugal settling is evaluated. The separation density at which 50% of the material of that density is recovered was found to increase from 0.010 to 0.026 g/cm 3 as the separation media density increased from 1.09 to 1.27 g/cm 3 . All separation medias were found to have significantly low Ep 95 values of 0.012-0.033 g/cm 3 . It is also demonstrated that the presence of an excess content of 75%) resulted in reduced separation efficiencies. It is shown that the optimum separations were achieved when the media density offset was 0.03-0.04 g/cm 3 . It is shown that effective heavy media cyclone separations of RP denser than 1.0 g/cm 3 can produce three sets of mixed plastics containing: PS and ABS/SAN at densities of >1.0-1.09 g/cm 3 ; PC, PMMA at a density of 1.09-1.18 g/cm 3 ; and PVC and PET at a density of >1.27 g/cm 3 . Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Hybrid-renewable processes for biofuels production: concentrated solar pyrolysis of biomass residues

    Energy Technology Data Exchange (ETDEWEB)

    George, Anthe [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Geier, Manfred [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States); Dedrick, Daniel E. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2014-10-01

    The viability of thermochemically-derived biofuels can be greatly enhanced by reducing the process parasitic energy loads. Integrating renewable power into biofuels production is one method by which these efficiency drains can be eliminated. There are a variety of such potentially viable "hybrid-renewable" approaches; one is to integrate concentrated solar power (CSP) to power biomass-to-liquid fuels (BTL) processes. Barriers to CSP integration into BTL processes are predominantly the lack of fundamental kinetic and mass transport data to enable appropriate systems analysis and reactor design. A novel design for the reactor has been created that can allow biomass particles to be suspended in a flow gas, and be irradiated with a simulated solar flux. Pyrolysis conditions were investigated and a comparison between solar and non-solar biomass pyrolysis was conducted in terms of product distributions and pyrolysis oil quality. A novel method was developed to analyse pyrolysis products, and investigate their stability.

  4. Wet high-intensity magnetic separation for the concentration of Witwatersrand gold-uranium ores and residues

    International Nuclear Information System (INIS)

    Corrans, I.J.; Levin, J.

    1979-01-01

    Wet high-intensity magnetic separation (WHIMS) for the concentration of gold and uranium was tested on many Witwatersrand cyanidation residues, and on some ores and flotation tailings. The results varied, but many indicated recoveries of over 60 per cent of the gold and uranium. The main source of loss is the inefficiency of WHIMS for material of smaller particle size than 20μm. The recoveries in the continuous tests were lower than those in the batch tests. The continuous tests indicated an operational difficulty that could be experienced in practice, namely the tendency for wood chips and ferromagnetic particles to block the matrix of the separator. It was decided that a solution to the problem lies in the modification of the separator to allow continuous removal of the matrix for cleaning. A system has been developed for this purpose and is being demonstrated on a pilot-plant scale. Promising results were obtained in tests on a process that combines a coarse grind, gravity concentration, and WHIMS. In the gravity-concentration step, considerable recoveries, generally over 50 per cent, of high-grade pyrite were obtained, together with high recoveries of gold and moderate, but possibly important, recoveries of uranium. A simple model describing the operation of the WHIMS machine in terms of the operating parameters is described. This should reduce the amount of empirical testwork required for the optimization of operating conditions and should provide a basis for scale-up calculations. The economics of the WHIMS process is discussed [af

  5. Residual sarcoplasmic reticulum Ca2+ concentration after Ca2+ release in skeletal myofibers from young adult and old mice.

    Science.gov (United States)

    Wang, Zhong-Min; Tang, Shen; Messi, María Laura; Yang, Jenny J; Delbono, Osvaldo

    2012-04-01

    Contrasting information suggests either almost complete depletion of sarcoplasmic reticulum (SR) Ca(2+) or significant residual Ca(2+) concentration after prolonged depolarization of the skeletal muscle fiber. The primary obstacle to resolving this controversy is the lack of genetically encoded Ca(2+) indicators targeted to the SR that exhibit low-Ca(2+) affinity, a fast biosensor: Ca(2+) off-rate reaction, and can be expressed in myofibers from adult and older adult mammalian species. This work used the recently designed low-affinity Ca(2+) sensor (Kd = 1.66 mM in the myofiber) CatchER (calcium sensor for detecting high concentrations in the ER) targeted to the SR, to investigate whether prolonged skeletal muscle fiber depolarization significantly alters residual SR Ca(2+) with aging. We found CatchER a proper tool to investigate SR Ca(2+) depletion in young adult and older adult mice, consistently tracking SR luminal Ca(2+) release in response to brief and repetitive stimulation. We evoked SR Ca(2+) release in whole-cell voltage-clamped flexor digitorum brevis muscle fibers from young and old FVB mice and tested the maximal SR Ca(2+) release by directly activating the ryanodine receptor (RyR1) with 4-chloro-m-cresol in the same myofibers. Here, we report for the first time that the Ca(2+) remaining in the SR after prolonged depolarization (2 s) in myofibers from aging (~220 μM) was larger than young (~132 μM) mice. These experiments indicate that SR Ca(2+) is far from fully depleted under physiological conditions throughout life, and support the concept of excitation-contraction uncoupling in functional senescent myofibers.

  6. Anti-tuberculosis drug concentrations in tuberculosis patients with and without diabetes mellitus.

    Science.gov (United States)

    Kumar, A K Hemanth; Chandrasekaran, V; Kannan, T; Murali, A Lakshmi; Lavanya, J; Sudha, V; Swaminathan, Soumya; Ramachandran, Geetha

    2017-01-01

    The aim of the study was to compare plasma concentrations of rifampicin (RMP), isoniazid (INH) and pyrazinamide (PZA) between tuberculosis (TB) patients with and without diabetes mellitus (DM). Two-hour post-dosing concentrations of RMP, INH and PZA were determined in adult TB patients that were studied with (n = 452) and without DM (n = 1460), treated with a thrice-weekly regimen in India. Drug concentrations were estimated by HPLC. The median (IQR) INH [6.6 (3.9-10.0) and 7.8 (4.6-11.3)] and PZA [31.0 (22.3-38.0) and 34.1 (24.6-42.7)] microgram per milliliter concentrations were significantly lower in diabetic than non-diabetic TB patients (p < 0.001 for both drugs). Blood glucose was negatively correlated with plasma INH (r = -0.09, p < 0.001) and PZA (r = -0.092, p < 0.001). Multiple linear regression analysis showed RMP, INH and PZA concentrations were influenced by age and drug doses, INH and PZA by DM, RMP by alcohol use and PZA by gender and category of ATT. DM reduced INH and PZA concentrations by 0.8 and 3.0 μg/ml, respectively. TB patients with DM had lower INH and PZA concentrations. Negative correlation between blood glucose and drug concentrations suggests delayed absorption/faster elimination of INH and PZA in the presence of elevated glucose.

  7. Reported prevalence and quantitative LC-MS methods for the analysis of veterinary drug residues in honey: a review.

    Science.gov (United States)

    Venable, Ryan; Haynes, Carion; Cook, Jo Marie

    2014-04-01

    Insect pollination increases the value and productivity of three-quarters of crop species grown for food. Declining beehive health in commercial apiaries has resulted in numerous reports from government laboratories worldwide of contamination with antimicrobial chemicals in honey. This review includes pertinent discussion of legislation and events leading to increased government oversight in the commercial honey market. A detailed summary of the variety and prevalence of veterinary drug residues being found in honey as well as a selection of robust quantitative and confirmatory LC-MS methods with an emphasis on those adopted by government testing laboratories are presented.

  8. Impact of the nature and concentration of plasticizers on the ability of PVC to sorb drug.

    Science.gov (United States)

    Al Salloum, H; Saunier, J; Aymes-Chodur, C; Barakat, H; Yagoubi, N

    2015-12-30

    The sorption of a drug by an infusion set may dramatically reduce the drug delivery efficiency. In this paper, we investigated how the drug sorption, in static conditions, is affected by the plasticizer's nature and ratio in the case of plasticized PVC, one of the most common material for infusion set tubing. Within the study, the drug concentration in diazepam solutions was studied after contact with PVC films containing different amounts of DEHP, DEHT, TOTM and DINCH® plasticizers. Moreover the partition coefficients between material and water were calculated. The drug sorption levels were equivalent for the different plasticizers and there was a plasticizer ratio for which the drug uptake was enhanced. As a consequence, the amount of sorbed drug might not be only linked to the amount of plasticizer in the film and to the solubility of the drug in the plasticizer alone: it must probably depend on specific interactions between plasticizer and PVC. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Observational assessment of the role of nocturnal residual-layer chemistry in determining daytime surface particulate nitrate concentrations

    Directory of Open Access Journals (Sweden)

    G. Prabhakar

    2017-12-01

    Full Text Available This study discusses an analysis of combined airborne and ground observations of particulate nitrate (NO3−(p concentrations made during the wintertime DISCOVER-AQ (Deriving Information on Surface Conditions from COlumn and VERtically resolved observations relevant to Air Quality study at one of the most polluted cities in the United States – Fresno, CA – in the San Joaquin Valley (SJV and focuses on developing an understanding of the various processes that impact surface nitrate concentrations during pollution events. The results provide an explicit case-study illustration of how nighttime chemistry can influence daytime surface-level NO3−(p concentrations, complementing previous studies in the SJV. The observations exemplify the critical role that nocturnal chemical production of NO3−(p aloft in the residual layer (RL can play in determining daytime surface-level NO3−(p concentrations. Further, they indicate that nocturnal production of NO3−(p in the RL, along with daytime photochemical production, can contribute substantially to the buildup and sustaining of severe pollution episodes. The exceptionally shallow nocturnal boundary layer (NBL heights characteristic of wintertime pollution events in the SJV intensify the importance of nocturnal production aloft in the residual layer to daytime surface concentrations. The observations also demonstrate that dynamics within the RL can influence the early-morning vertical distribution of NO3−(p, despite low wintertime wind speeds. This overnight reshaping of the vertical distribution above the city plays an important role in determining the net impact of nocturnal chemical production on local and regional surface-level NO3−(p concentrations. Entrainment of clean free-tropospheric (FT air into the boundary layer in the afternoon is identified as an important process that reduces surface-level NO3−(p and limits buildup during pollution episodes. The influence of dry deposition of HNO

  10. Observational assessment of the role of nocturnal residual-layer chemistry in determining daytime surface particulate nitrate concentrations

    Science.gov (United States)

    Prabhakar, Gouri; Parworth, Caroline L.; Zhang, Xiaolu; Kim, Hwajin; Young, Dominique E.; Beyersdorf, Andreas J.; Ziemba, Luke D.; Nowak, John B.; Bertram, Timothy H.; Faloona, Ian C.; Zhang, Qi; Cappa, Christopher D.

    2017-12-01

    This study discusses an analysis of combined airborne and ground observations of particulate nitrate (NO3-(p)) concentrations made during the wintertime DISCOVER-AQ (Deriving Information on Surface Conditions from COlumn and VERtically resolved observations relevant to Air Quality) study at one of the most polluted cities in the United States - Fresno, CA - in the San Joaquin Valley (SJV) and focuses on developing an understanding of the various processes that impact surface nitrate concentrations during pollution events. The results provide an explicit case-study illustration of how nighttime chemistry can influence daytime surface-level NO3-(p) concentrations, complementing previous studies in the SJV. The observations exemplify the critical role that nocturnal chemical production of NO3-(p) aloft in the residual layer (RL) can play in determining daytime surface-level NO3-(p) concentrations. Further, they indicate that nocturnal production of NO3-(p) in the RL, along with daytime photochemical production, can contribute substantially to the buildup and sustaining of severe pollution episodes. The exceptionally shallow nocturnal boundary layer (NBL) heights characteristic of wintertime pollution events in the SJV intensify the importance of nocturnal production aloft in the residual layer to daytime surface concentrations. The observations also demonstrate that dynamics within the RL can influence the early-morning vertical distribution of NO3-(p), despite low wintertime wind speeds. This overnight reshaping of the vertical distribution above the city plays an important role in determining the net impact of nocturnal chemical production on local and regional surface-level NO3-(p) concentrations. Entrainment of clean free-tropospheric (FT) air into the boundary layer in the afternoon is identified as an important process that reduces surface-level NO3-(p) and limits buildup during pollution episodes. The influence of dry deposition of HNO3 gas to the surface on

  11. Semiconducting iron silicide thin films on silicon (111) with large Hall mobility and low residual electron concentration

    Science.gov (United States)

    Muret, P.; Ali, I.; Brunel, M.

    1998-10-01

    Unprecedented Hall mobility, electron concentration and photoconductivity are demonstrated in semiconducting 0268-1242/13/10/020/img6-0268-1242/13/10/020/img7 thin films prepared on Si(111) surfaces by co-sputtering of iron and silicon followed by post-anneal. Characterization of the silicide as a function of the initial temperature and post-treatment shows that annealing temperatures above 0268-1242/13/10/020/img8C are needed to obtain single phase 0268-1242/13/10/020/img6-0268-1242/13/10/020/img7. Reactive deposition on substrates heated at 0268-1242/13/10/020/img11C leads to textured films. Majority carriers are electrons in all these unintentionally doped films. Hall concentrations between 0268-1242/13/10/020/img12 and 0268-1242/13/10/020/img13 electrons 0268-1242/13/10/020/img14 and respective Hall mobilities from 290 to 0268-1242/13/10/020/img15 are measured at room temperature, involving two different conduction band minima in these two extreme cases. Only deep centres exist in the samples having the lower carrier concentration. In such a situation, raw data must be corrected for the substrate contribution to extract values which are relevant for the 0268-1242/13/10/020/img6-0268-1242/13/10/020/img7 film alone. Photoconductivity also takes place in these samples: at 80 K, it shows a maximum value at the direct band gap of 0268-1242/13/10/020/img6-0268-1242/13/10/020/img7 while at 296 K a step still appears at the same energy. Such results are a consequence of the important decrease of the residual impurity concentration in comparison to values previously published.

  12. Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics

    Science.gov (United States)

    2012-01-01

    Introduction In order to assess the significance of drug levels measured in intensive care medicine, clinical and forensic toxicology, as well as for therapeutic drug monitoring, it is essential that a comprehensive collection of data is readily available. Therefore, it makes sense to offer a carefully referenced compilation of therapeutic and toxic plasma concentration ranges, as well as half-lives, of a large number of drugs and other xenobiotics for quick and comprehensive information. Methods Data have been abstracted from original papers and text books, as well as from previous compilations, and have been completed with data collected in our own forensic and clinical toxicology laboratory. The data presented in the table and corresponding annotations have been developed over the past 20 years and longer. A previous compilation has been completely revised and updated. In addition, more than 170 substances, especially drugs that have been introduced to the market since 2003 as well as illegal drugs, which became known to cause intoxications, were added. All data were carefully referenced and more than 200 new references were included. Moreover, the annotations providing details were completely revised and more than 100 annotations were added. Results For nearly 1,000 drugs and other xenobiotics, therapeutic ("normal") and, if data were available, toxic and comatose-fatal blood-plasma concentrations and elimination half-lives were compiled in a table. Conclusions In case of intoxications, the concentration of the ingested substances and/or metabolites in blood plasma better predicts the clinical severity of the case when compared to the assumed amount and time of ingestion. Comparing and contrasting the clinical case against the data provided, including the half-life, may support the decision for or against further intensive care. In addition, the data provided are useful for the therapeutic monitoring of pharmacotherapies, to facilitate the diagnostic assessment

  13. Relationships of serum illicit drug concentrations during pregnancy to maternal nutritional status.

    Science.gov (United States)

    Knight, E M; James, H; Edwards, C H; Spurlock, B G; Oyemade, U J; Johnson, A A; West, W L; Cole, O J; Westney, L S; Westney, O E

    1994-06-01

    Findings reported are for a subset of African American subjects, residing in the urban area of Washington, D. C., who participated in a Program Project designed to study nutrition, other factors, and the outcome of pregnancy. Fasting blood samples, drawn during each trimester of pregnancy and at delivery, were screened for concentrations of cocaine, phencyclidine (PCP) and marijuana. Since substance abusers are expected to consume inadequate diets, these samples were also analyzed for serum folate, vitamin B12, ferritin and ascorbic acid. Data for these biochemical variables were compared for subjects whose serum values for drugs were either above or below the drug screening threshold concentrations established by ADAMHA/NIDA. Pearson's correlations were used to determine relationships between pregnancy outcome variables and maternal serum drug concentrations. Blood samples drawn at delivery showed higher maternal: cord ratios (mean +/- SEM) for marijuana (3.3 +/- 2.2) and PCP (2.9 +/- 1.0) than for cocaine (1.0 +/- 0.2). The subjects whose serum values were above the ADAMHA/NIDA ranges for marijuana, PCP and cocaine had concentrations of folate and ferritin that were significantly less than those of subjects with lower serum drug levels (P illicit drugs were accompanied by a significant increase in leukocyte count (P < or = 0.05). The level of maternal cocaine during the third trimester was inversely correlated with birthweight (r = -0.29; n = 52; P = 0.038) and head circumference (r = -0.28; n = 52; P = 0.047).(ABSTRACT TRUNCATED AT 250 WORDS)

  14. 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

  15. Development of Radiometric and Allied Analytical Methods and Strategies to Strengthen National Residue Control Programmes for Antibiotic and Anthelmintic Veterinary Drug Residues. Final Report of a Coordinated Research Project

    International Nuclear Information System (INIS)

    2016-08-01

    Awareness of food safety is rising among consumers, and many importing countries implement food control regulations to guarantee the quality and safety of imported foods for their consumers. Many developing countries have also taken steps to put in place control systems that encourage responsible use of veterinary medicines to combat possible drug resistance, control drug residues and ensure compliance with international and national standards. However, these countries still require the necessary know-how and skills to protect local consumers and to access international markets. One significant constraint is the capacity of laboratory services to generate surveillance data using reliable and cost effective analytical methods validated to national and international standards. The IAEA coordinated research project (CRP) on the Development of Radiometric and Allied Analytical Methods to Strengthen National Residue Control Programmes for Antibiotic and Anthelmintic Veterinary Drug Residues was initiated in 2009 to conduct work on robust nuclear and related technologies suitable for the screening and confirmatory analysis of residues of veterinary medicines, including antimicrobials and anthelmintics commonly used in animal production, with public health and trade significance. The CRP also explored mechanisms to enhance networking among research institutions involved in research on pharmacologically active veterinary drug residues in food (primarily) and environmental samples. The project was implemented by the Joint FAO/IAEA Division of Nuclear Techniques in Food and Agriculture between 2009 and 2014 and involved eleven research contracts and one technical contract, five research agreements and one institution. The CRP was a continuation of the CRP on the Development of Strategies for the Effective Monitoring of Veterinary Drug Residues in Livestock and Livestock Products in Developing Countries and the key findings are also summarized in this publication.

  16. Residues of veterinary drugs in eggs and their distribution between yolk and white

    NARCIS (Netherlands)

    Kan, C.A.; Petz, M.

    2000-01-01

    Veterinary drugs and feed additives (especially some coccidiostats) can be absorbed by the digestive tract of laying hens and transferred to the egg. Physicochemical characteristics of these compounds determine their pharmacokinetic behavior and distribution to and within the egg. Traditionally the

  17. Relationship between RFC gene expression and intracellular drug concentration in methotrexate-resistant osteosarcoma cells.

    Science.gov (United States)

    Wang, J J; Li, G J

    2014-07-24

    Osteosarcoma is a primary malignant tumor in adolescents, associated with high mortality and morbidity. The high-dose methotrexate (MTX) chemotherapy used to treat this disease may induce primary or secondary drug resistance, resulting in a reduced effect of comprehensive treatment. In this study, the relationship between reduced folate carrier (RFC) gene expression and intracellular drug concentration in MTX-resistant osteosarcoma cells (Saos-2) was investigated. MTX-resistant human osteosarcoma cells (Saos-2/MTX2.2, Saos-2/MTX4.4) were prepared. The sensitivities of Saos-2 (primary cells), Saos-2/MTX2.2, and Saos-2/MTX4.4 cells to MTX, diamminedichloroplatinum (DDP), ifosfamide (IFO), epirubicine (EPI), adriamycin (ADM), theprubicin (THP), and paclitaxel (PTX) were detected by MTT. The median inhibitory concentration (IC50) and resistance index were measured. Semi-quantitative RT-PCR was used to evaluate the expression of RFC gene in cells. The intracellular (3)H-MTX concentration was determined. Results showed that IC50 of Saos-2/MTX2.2 and Saos-2/MTX4.4 was 4.87 and 12.73 times that of Saos-2, respectively. Both Saos-2/MTX2.2 and Saos-2/MTX4.4 had resistance to IFO, ADM, EPI, THP, and PTX, but not DDP. Compared to Saos-2/MTX2.2 and Saos-2/MTX4.4, the expression of RFC mRNA in Saos-2 was significantly higher. The intracellular (3)H-MTX concentration reached a peak at 50 min. After 70 min, the concentration was maintained at a plateau. During this phase, the (3)H-MTX concentration in Saos-2 cells was 2.15 times higher than the concentration in Saos-2/MTX4.4 cells. The reduced RFC mRNA expression in PTX-resistant osteosarcoma cells may be related to the decrease in intracellular (3)H-MTX concentration.

  18. Cheburator software for automatically calculating drug inhibitory concentrations from in vitro screening assays.

    Directory of Open Access Journals (Sweden)

    Dmitry Nevozhay

    Full Text Available In the process of new cancer drug development, as the first step of their assessment, their activities are usually studied in vitro against a panel of cancer cell lines. The results of these in vitro drug screening assays are commonly expressed as inhibitory concentration 50% (IC50: the concentration of the tested agent that inhibits the proliferation of the cancer cell population to 50% of the theoretically possible effect (absolute IC50 or maximum effect practically achieved by the drug (relative IC50. The currently available software for calculating IC50 values requires manual data entry, is time consuming, and is prone to calculation errors. Thus, we have developed open source, free, easy-to-use software for performing standardized data evaluations and automatically calculating the IC50. This software eliminates the laborious and error-prone manual entry of data, substantially reduces the amount of time spent for data analysis. It has been extensively used in our department as the main tool for in vitro data processing during the past several years and can be useful for other research groups working in the area of anticancer drug discovery, either alone or combined with other software packages. The current version of our program, Cheburator, together with sample data, source code, and documentation, is freely available at the following URL: http://www.cheburator.nevozhay.com (it is free for academic use, but a license is required for commercial use.

  19. Computational Biology Tools for Identifying Specific Ligand Binding Residues for Novel Agrochemical and Drug Design.

    Science.gov (United States)

    Neshich, Izabella Agostinho Pena; Nishimura, Leticia; de Moraes, Fabio Rogerio; Salim, Jose Augusto; Villalta-Romero, Fabian; Borro, Luiz; Yano, Inacio Henrique; Mazoni, Ivan; Tasic, Ljubica; Jardine, Jose Gilberto; Neshich, Goran

    2015-01-01

    The term "agrochemicals" is used in its generic form to represent a spectrum of pesticides, such as insecticides, fungicides or bactericides. They contain active components designed for optimized pest management and control, therefore allowing for economically sound and labor efficient agricultural production. A "drug" on the other side is a term that is used for compounds designed for controlling human diseases. Although drugs are subjected to much more severe testing and regulation procedures before reaching the market, they might contain exactly the same active ingredient as certain agrochemicals, what is the case described in present work, showing how a small chemical compound might be used to control pathogenicity of Gram negative bacteria Xylella fastidiosa which devastates citrus plantations, as well as for control of, for example, meningitis in humans. It is also clear that so far the production of new agrochemicals is not benefiting as much from the in silico new chemical compound identification/discovery as pharmaceutical production. Rational drug design crucially depends on detailed knowledge of structural information about the receptor (target protein) and the ligand (drug/agrochemical). The interaction between the two molecules is the subject of analysis that aims to understand relationship between structure and function, mainly deciphering some fundamental elements of the nanoenvironment where the interaction occurs. In this work we will emphasize the role of understanding nanoenvironmental factors that guide recognition and interaction of target protein and its function modifier, an agrochemical or a drug. The repertoire of nanoenvironment descriptors is used for two selected and specific cases we have approached in order to offer a technological solution for some very important problems that needs special attention in agriculture: elimination of pathogenicity of a bacterium which is attacking citrus plants and formulation of a new fungicide. Finally

  20. RISKS ASSOCIATED WITH THE PRESENCE OF ANTIMICROBIAL DRUG RESIDUES IN MEAT PRODUCTS AND PRODUCTS OF ANIMAL SLAUGHTER

    Directory of Open Access Journals (Sweden)

    D. S. Bataeva

    2016-01-01

    Full Text Available The risks associated with the presence of antimicrobial drug residues in meat and products of animal slaughter were determined. One of them is the emergence of antimicrobial resistance in pathogenic and conditionally pathogenic microorganisms isolated from meat and products of animal slaughter. It was established that Escherichia coli, Salmonella and Pseudomonas were resistant to ampicillin, tetracycline, tylosin and cephalolexin. However, Listeria monocytogenes did not have resistance to these antibiotics. It was also established that when entering an animal body, antimicrobials were accumulated mostly in liver and kidneys of an animal followed by meat and, to the least degree, in fat. It was found that up to 65% of the tested samples were contaminated with antimicrobials to a greater or lesser degree.

  1. Analytical quality assurance in veterinary drug residue analysis methods: matrix effects determination and monitoring for sulfonamides analysis.

    Science.gov (United States)

    Hoff, Rodrigo Barcellos; Rübensam, Gabriel; Jank, Louise; Barreto, Fabiano; Peralba, Maria do Carmo Ruaro; Pizzolato, Tânia Mara; Silvia Díaz-Cruz, M; Barceló, Damià

    2015-01-01

    In residue analysis of veterinary drugs in foodstuff, matrix effects are one of the most critical points. This work present a discuss considering approaches used to estimate, minimize and monitoring matrix effects in bioanalytical methods. Qualitative and quantitative methods for estimation of matrix effects such as post-column infusion, slopes ratios analysis, calibration curves (mathematical and statistical analysis) and control chart monitoring are discussed using real data. Matrix effects varying in a wide range depending of the analyte and the sample preparation method: pressurized liquid extraction for liver samples show matrix effects from 15.5 to 59.2% while a ultrasound-assisted extraction provide values from 21.7 to 64.3%. The matrix influence was also evaluated: for sulfamethazine analysis, losses of signal were varying from -37 to -96% for fish and eggs, respectively. Advantages and drawbacks are also discussed considering a workflow for matrix effects assessment proposed and applied to real data from sulfonamides residues analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Biochemical changes and drug residues in ascidian Halocynthia roretzi after formalin–hydrogen peroxide treatment regimen designed against soft tunic syndrome

    Directory of Open Access Journals (Sweden)

    Ji-Hoon Lee

    2017-07-01

    Full Text Available Abstract Soft tunic syndrome (STS is a protozoal disease caused by Azumiobodo hoyamushi in the edible ascidian Halocynthia roretzi. Previous studies have proven that combined formalin–hydrogen peroxide (H2O2 bath is effective in reducing STS progress and mortality. To secure target animal safety for field applications, toxicity of the treatment needs to be evaluated. Healthy ascidians were bathed for 1 week, 1 h a day at various bathing concentrations. Bathing with 5- and 10-fold optimum concentration caused 100% mortality of ascidians, whereas mortality by 0.5- to 2.0-fold solutions was not different from that of control. Of the oxidative damage parameters, MDA levels did not change after 0.5- and 1.0-fold bathing. However, free radical scavenging ability and reducing power were significantly decreased even with the lower-than-optimal 0.5-fold concentration. Glycogen content tended to increase with 1-fold bathing without statistical significance. All changes induced by the 2-fold bathing were completely or partially restored to control levels 48 h post-bathing. Free amino acid analysis revealed a concentration-dependent decline in aspartic acid and cysteine levels. In contrast, alanine and valine levels increased after the 2-fold bath treatment. These data indicate that the currently established effective disinfectant regimen against the parasitic pathogen is generally safe, and the biochemical changes observed are transient, lasting approximately 48 h at most. Low levels of formalin and H2O2 were detectable 1 h post-bathing; however, the compounds were completely undetectable after 48 h of bathing. Formalin–H2O2 bathing is effective against STS; however, reasonable care is required in the treatment to avoid unwanted toxicity. Drug residues do not present a concern for consumer safety.

  3. 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.

  4. Physiological concentrations of zinc reduce taurine-activated GlyR responses to drugs of abuse

    Science.gov (United States)

    Kirson, Dean; Cornelison, Garrett L.; Philpo, Ashley E.; Todorovic, Jelena; Mihic, S. John

    2013-01-01

    Taurine is an endogenous ligand acting on glycine receptors in many brain regions, including the hippocampus, prefrontal cortex, and nucleus accumbens (nAcc). These areas also contain low concentrations of zinc, which is known to potentiate glycine receptor responses. Despite an increasing awareness of the role of the glycine receptor in the rewarding properties of drugs of abuse, the possible interactions of these compounds with zinc has not been thoroughly addressed. Two-electrode voltage-clamp electrophysiological experiments were performed on α1, α2 α1β and a2β glycine receptors expressed in Xenopus laevis oocytes. The effects of zinc alone, and zinc in combination with other positive modulators on the glycine receptor, were investigated when activated by the full agonist glycine versus the partial agonist taurine. Low concentrations of zinc enhanced responses of maximally-effective concentrations of taurine but not glycine. Likewise, chelation of zinc from buffers decreased responses of taurine- but not glycine-mediated currents. Potentiating concentrations of zinc decreased ethanol, isoflurane, and toluene enhancement of maximal taurine currents with no effects on maximal glycine currents. Our findings suggest that the concurrence of high concentrations of taurine and low concentrations of zinc attenuate the effects of additional modulators on the glycine receptor, and that these conditions are more representative of in vivo functioning than effects seen when these modulators are applied in isolation. PMID:23973295

  5. Application and evaluation of a high-resolution mass spectrometry screening method for veterinary drug residues in incurred fish and imported aquaculture samples.

    Science.gov (United States)

    Turnipseed, Sherri B; Storey, Joseph M; Wu, I-Lin; Gieseker, Charles M; Hasbrouck, Nicholas R; Crosby, Tina C; Andersen, Wendy C; Lanier, Shanae; Casey, Christine R; Burger, Robert; Madson, Mark R

    2018-02-14

    The ability to detect chemical contaminants, including veterinary drug residues in animal products such as fish, is an important example of food safety analysis. In this paper, a liquid chromatography high-resolution mass spectrometry (LC-HRMS) screening method using a quadrupole-Orbitrap instrument was applied to the analysis of veterinary drug residues in incurred tissues from aquacultured channel catfish, rainbow trout, and Atlantic salmon and imported aquacultured products including European eel, yellow croaker, and tilapia. Compared to traditional MS methods, the use of HRMS with nontargeted data acquisition and exact mass measurement capability greatly increased the scope of compounds that could be monitored simultaneously. The fish samples were prepared for analysis using a simple efficient procedure that consisted of an acidic acetonitrile extraction followed by solid phase extraction cleanup. Two different HRMS acquisition programs were used to analyze the fish extracts. This method detected and identified veterinary drugs including quinolones, fluoroquinolones, avermectins, dyes, and aminopenicillins at residue levels in fish that had been dosed with those compounds. A metabolite of amoxicillin, amoxicillin diketone, was also found at high levels in catfish, trout, and salmon. The method was also used to characterize drug residues in imported fish. In addition to confirming findings of fluoroquinolone and sulfonamide residues that were found by traditional targeted MS methods, several new compounds including 2-amino mebendazole in eel and ofloxacin in croaker were detected and identified. Graphical Abstract Aquacultured samples are analyzed with a high-resolution mass spectrometry screening method to detect and identify unusual veterinary drug residues including ofloxacin in an imported fish.

  6. Psychotropic drugs in mixture alter swimming behaviour of Japanese medaka (Oryzias latipes) larvae above environmental concentrations.

    Science.gov (United States)

    Chiffre, Axelle; Clérandeau, Christelle; Dwoinikoff, Charline; Le Bihanic, Florane; Budzinski, Hélène; Geret, Florence; Cachot, Jérôme

    2016-03-01

    Psychiatric pharmaceuticals, such as anxiolytics, sedatives, hypnotics and antidepressors, are among the most prescribed active substances in the world. The occurrence of these compounds in the environment, as well as the adverse effects they can have on non-target organisms, justifies the growing concern about these emerging environmental pollutants. This study aims to analyse the effects of six psychotropic drugs, valproate, cyamemazine, citalopram, sertraline, fluoxetine and oxazepam, on the survival and locomotion of Japanese medaka Oryzias latipes larvae. Newly hatched Japanese medaka were exposed to individual compounds for 72 h, at concentrations ranging from 10 μg L(-1) to 10 mg L(-1). Lethal concentrations 50 % (LC50) were estimated at 840, 841 and 9,136 μg L(-1) for fluoxetine, sertraline and citalopram, respectively, while other compounds did not induce any significant increase in mortality. Analysis of the swimming behaviour of larvae, including total distance moved, mobility and location, provided an estimated lowest observed effect concentration (LOEC) of 10 μg L(-1) for citalopram and oxazepam, 12.2 μg L(-1) for cyamemazine, 100 μg L(-1) for fluoxetine, 1,000 μg L(-1) for sertraline and >10,000 μg L(-1) for valproate. Realistic environmental mixture of the six psychotropic compounds induced disruption of larval locomotor behaviour at concentrations about 10- to 100-fold greater than environmental concentrations.

  7. 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.

  8. Veterinary Drugs and Growth Promoters Residues in Meat and Processed Meats

    Science.gov (United States)

    Reig, Milagro; Toldrá, Fidel

    Veterinary drugs, which comprise a large number of different types of substances, are generally intended for therapeutic (to control infectious diseases) and prophylactic (to prevent against infections) purposes in farm animals. Other substances with growth promoting effect may exert antimicrobial effect against the microbial flora in the gut to take maximum profit of nutrients in the feed or by affecting the animal’s metabolism. Most of these substances are orally active and can be administered either in the feed or in the drinking water. Other active hormones are applied in the form of small implants into the subcutaneous tissue of the ears. These are slow release (several weeks or months) devices and the ears are discarded at the slaughter. Growth promoters allow a better efficiency in the feed conversion rate. The net effect is an increased protein deposition, partly due to muscle proteases inhibition (Fiems, Buts, Boucque, Demeyer, & Cottyn, 1990), usually linked to fat utilization (Brockman & Laarveld, 1986). The result is a leaner meat (Lone, 1997) with some toughness derived from the production of connective tissue and collagen crosslinking (Miller, Judge, Diekman, Hudgens, & Aberle, 1989; Miller, Judge, & Schanbacher, 1990). Some recent fraudulent practices, consisting of the use of a kind of “cocktails” or mixtures of several substances like β-agonists and corticosteroids at very low amounts (Monsón et al., 2007), are difficult to detect with modern analytical instrumentation. They try to obtain a synergistic effect for a similar growth promotion with lower probability of detection by official control laboratories (Reig & Toldrá, 2007).

  9. Determination of residual acetone and acetone related impurities in drug product intermediates prepared as Spray Dried Dispersions (SDD) using gas chromatography with headspace autosampling (GCHS).

    Science.gov (United States)

    Quirk, Emma; Doggett, Adrian; Bretnall, Alison

    2014-08-05

    Spray Dried Dispersions (SDD) are uniform mixtures of a specific ratio of amorphous active pharmaceutical ingredient (API) and polymer prepared via a spray drying process. Volatile solvents are employed during spray drying to facilitate the formation of the SDD material. Following manufacture, analytical methodology is required to determine residual levels of the spray drying solvent and its associated impurities. Due to the high level of polymer in the SDD samples, direct liquid injection with Gas Chromatography (GC) is not a viable option for analysis. This work describes the development and validation of an analytical approach to determine residual levels of acetone and acetone related impurities, mesityl oxide (MO) and diacetone alcohol (DAA), in drug product intermediates prepared as SDDs using GC with headspace (HS) autosampling. The method development for these analytes presented a number of analytical challenges which had to be overcome before the levels of the volatiles of interest could be accurately quantified. GCHS could be used after two critical factors were implemented; (1) calculation and application of conversion factors to 'correct' for the reactions occurring between acetone, MO and DAA during generation of the headspace volume for analysis, and the addition of an equivalent amount of polymer into all reference solutions used for quantitation to ensure comparability between the headspace volumes generated for both samples and external standards. This work describes the method development and optimisation of the standard preparation, the headspace autosampler operating parameters and the chromatographic conditions, together with a summary of the validation of the methodology. The approach has been demonstrated to be robust and suitable to accurately determine levels of acetone, MO and DAA in SDD materials over the linear concentration range 0.008-0.4μL/mL, with minimum quantitation limits of 20ppm for acetone and MO, and 80ppm for DAA. Copyright

  10. 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.

  11. Time-course measurements of drug concentrations in hair and toenails after single administrations of pharmaceutical products.

    Science.gov (United States)

    Kuwayama, Kenji; Miyaguchi, Hajime; Iwata, Yuko T; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Yamamuro, Tadashi; Segawa, Hiroki; Inoue, Hiroyuki

    2017-04-01

    Hair and nails are often used to prove long-term intake of drugs in forensic drug testing. The aim of this study was to evaluate the effectiveness of drug testing using hair and nails and the feasibility of determining when drugs were ingested by measuring the time-courses of drug concentrations in hair and toenails after single administrations of various drugs. Healthy subjects ingested four pharmaceutical products containing eight active ingredients in single doses. Hair and toenails were collected at predetermined intervals, and drug concentrations in hair and nails were measured for 12 months. The administered drugs and their main metabolites were extracted using micropulverized extraction with a stainless steel bullet and were analyzed using liquid chromatography/tandem mass spectrometry. Acidic compounds such as ibuprofen and its metabolites were not detected in both specimens. Acetaminophen, a weakly acidic compound, was detected in nails more frequently than in hair. The maximum concentration of allyl isopropyl acetylurea, a neutral compound, in nails was significantly higher than in hair. Nails are an effective specimen to detect neutral and weakly acidic compounds. For fexofenadine, a zwitterionic compound, and for most basic compounds, the maximum concentrations in hair segments tended to be higher than those in nails. The hair segments showing the maximum concentrations varied between drugs, samples, and subjects. Drug concentrations in hair segments greatly depended on the selection of the hair. Careful interpretation of analytical results is required to predict the time of drug intake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    di Cagno, Massimiliano Pio; Clarelli, Fabrizio; Våbenø, Jon; Lesley, Christina; Rahman, Sokar Darsim; Cauzzo, Jennifer; Franceschinis, Erica; Realdon, Nicola; Stein, Paul C

    2018-04-02

    The diffusion coefficient (also known as diffusivity) of an active pharmaceutical ingredient (API) is a fundamental physicochemical parameter that affects passive diffusion through biological barriers and, as a consequence, bioavailability and biodistribution. However, this parameter is often neglected, and it is quite difficult to find diffusion coefficients of small molecules of pharmaceutical relevance in the literature. The available methods to measure diffusion coefficients of drugs all suffer from limitations that range from poor sensitivity to high selectivity of the measurements 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 of a substance during spontaneous migration of molecules, followed by standard mathematical treatment of the data in order to solve Fick's law of diffusion. This method is extremely sensitive and results in highly reproducible data. The technique was also employed to verify the influence of the environmental 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 in physiological conditions and help to better understand the drug permeability process.

  13. Determination of Anthracycline Drug Residual in Cleaning Validation Swabs of Stainless-Steel Equipment after Production of Cytostatic Injections Using HPLC Analytical Method

    Directory of Open Access Journals (Sweden)

    Zuzana Slivová

    2015-01-01

    Full Text Available Standard cleaning procedures of production line equipment were verified after manufacture of cytostatic injections containing Anthracycline derivate substance. Residual content of Anthracycline drug substance on stainless-steel equipment surface was determined using swab sampling with a specific HPLC-DAD analysis. The acceptance limit was decided as 200.0 μg/100 cm2. Recovery from the stainless-steel surface was 90.1%. Linearity of the method was observed in the concentration range of 0.155–194 μg/mL when estimated using Zorbax TMS (5 μm, 0.25 m × 4.6 mm ID column at 1.3 mL/min flow rate and 254 nm (DAD 190–600 nm. The mobile phase consisted of lauryl hydrogen sulphate solution (3.7 g/L : methanol : acetonitrile (54 : 16 : 30, v/v/v with pH adjusted to 2.5 using phosphoric acid (85%. The LOD and LOQ for Anthracycline derivate were found to be 0.047 and 0.155 μg/mL, respectively. The method validation confirmed the method provides acceptable degree of selectivity, linearity, accuracy, and precision for the intended purposes.

  14. Analysis of veterinary drug and pesticide residues in animal feed by high-resolution mass spectrometry: comparison between time-of-flight and Orbitrap.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Romero-González, Roberto; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2015-01-01

    The use of medium-high-resolution mass spectrometers (M-HRMS) provides many advantages in multi-residue analysis. A comparison between two mass spectrometers, medium-resolution (MRMS) time-of-flight (TOF) and high-resolution (HRMS) Orbitrap, has been carried out for the analysis of toxic compounds in animal feed. More than 300 compounds belonging to several classes of veterinary drugs (VDs) and pesticides have been determined in different animal feed samples using a generic extraction method. The use of a clean-up procedure has been evaluated in both instruments, and several validation parameters have been established, such as the matrix effect, linearity, recovery and sensitivity. Finally, both instruments have been used during the analysis of 18 different feed samples (including chicken, hen, rabbit and horse). Some VDs (sulfadiazine, trimethoprim, robenidine and monensin sodium) and one pesticide (chlorpyrifos) have been identified. In general, better results were obtained using the Orbitrap, such as sensitivity (1-12.5 µg kg(-1)) and recovery values (60-125%). Moreover, this analyser had several software tools, which reduced the time for data processing and were easy to use, performing quick screening for more than 450 compounds in less than 5 min. However, some disadvantages such as the high cost and a decrease in the number of detected compounds at low concentrations must be taken into account.

  15. 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

  16. A self-assembled nanocarrier loading teniposide improves the oral delivery and drug concentration in tumor.

    Science.gov (United States)

    Zhang, Zhiwen; Ma, Li; Jiang, Shijun; Liu, Zeying; Huang, Jian; Chen, Lingli; Yu, Haijun; Li, Yaping

    2013-02-28

    We attempted to improve the oral delivery of lipophilic teniposide to achieve higher drug concentration in tumor by self-assembled nanocarrier for further oral chemotherapy. The teniposide loaded self-assembled nanocarrier (TSN) was spherical nanometric particles with narrow size distribution. The intestinal absorption of teniposide from TSN was obviously improved 4.09- and 6.35-fold in duodenum and jejunum at 0.5h after oral administration, then significantly decreased with the prolongation of time. The cellular uptake of TSN in Caco-2 cell monolayer was significantly enhanced over 3 folds and increased with incubation time. Moreover, TSN could be internalized into Caco-2 cell monolayer through clathrin-mediated endocytosis pathway, and then mainly transported into the systemic circulation via portal vein and intestinal lymphatic pathway. The pharmacokinetic results indicated that the AUC(0-t) value of TSN in rats was significantly improved 5.41-fold than that of teniposide solution, moreover, the teniposide concentration in tumor from TSN was obviously improved over 7-fold in tumor bearing mice. The captured image indicated that the oral administered TSN could specifically accumulate in tumor in the xenograft model. Therefore, the self-assembled nanocarrier was promising to enhance the oral delivery of lipophilic teniposide and its concentration in tumor for oral chemotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Feeding toxicity and impact of imidacloprid formulation and mixtures with six representative pesticides at residue concentrations on honey bee physiology (Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Yu Cheng Zhu

    Full Text Available Imidacloprid is the most widely used insecticide in agriculture. In this study, we used feeding methods to simulate in-hive exposures of formulated imidacloprid (Advise® 2FL alone and mixtures with six representative pesticides for different classes. Advise, fed at 4.3 mg/L (equal to maximal residue detection of 912 ppb active ingredient [a.i.] in pollen induced 36% mortality and 56% feeding suppression after 2-week feeding. Treatments with individual Bracket (acephate, Karate (λ-cyhalothrin, Vydate (oxamyl, Domark (tetraconazole, and Roundup (glyphosate at residue level had a mortality range of 1.3-13.3%, statistically similar to that of control (P>0.05. The additive/synergistic toxicity was not detected from binary mixtures of Advise with different classes of pesticides at residue levels. The feeding of the mixture of all seven pesticides increased mortality to 53%, significantly higher than Advise only but still without synergism. Enzymatic data showed that activities of invertase, glutathione S-transferase, and acetylcholinesterase activities in imidacloprid-treated survivors were mostly similar to those found in control. Esterase activity mostly increased, but was significantly suppressed by Bracket (acephate. The immunity-related phenoloxidase activity in imidacloprid-treated survivors tended to be lower, but most treatments were statistically similar to the control. Increase of cytochrome P450 activity was correlated with Advise concentrations and reached significant difference at 56 mg/L (12 ppm a.i.. Our data demonstrated that residue levels of seven pesticide in pollens/hive may not adversely affect honey bees, but long term exclusive ingestion of the maximal residue levels of imidacloprid (912 ppb and sulfoxaflor (3 ppm a.i. may induce substantial bee mortality. Rotating with other insecticides is a necessary and practical way to reduce the residue level of any given pesticide.

  18. Feeding toxicity and impact of imidacloprid formulation and mixtures with six representative pesticides at residue concentrations on honey bee physiology (Apis mellifera).

    Science.gov (United States)

    Zhu, Yu Cheng; Yao, Jianxiu; Adamczyk, John; Luttrell, Randall

    2017-01-01

    Imidacloprid is the most widely used insecticide in agriculture. In this study, we used feeding methods to simulate in-hive exposures of formulated imidacloprid (Advise® 2FL) alone and mixtures with six representative pesticides for different classes. Advise, fed at 4.3 mg/L (equal to maximal residue detection of 912 ppb active ingredient [a.i.] in pollen) induced 36% mortality and 56% feeding suppression after 2-week feeding. Treatments with individual Bracket (acephate), Karate (λ-cyhalothrin), Vydate (oxamyl), Domark (tetraconazole), and Roundup (glyphosate) at residue level had a mortality range of 1.3-13.3%, statistically similar to that of control (P>0.05). The additive/synergistic toxicity was not detected from binary mixtures of Advise with different classes of pesticides at residue levels. The feeding of the mixture of all seven pesticides increased mortality to 53%, significantly higher than Advise only but still without synergism. Enzymatic data showed that activities of invertase, glutathione S-transferase, and acetylcholinesterase activities in imidacloprid-treated survivors were mostly similar to those found in control. Esterase activity mostly increased, but was significantly suppressed by Bracket (acephate). The immunity-related phenoloxidase activity in imidacloprid-treated survivors tended to be lower, but most treatments were statistically similar to the control. Increase of cytochrome P450 activity was correlated with Advise concentrations and reached significant difference at 56 mg/L (12 ppm a.i.). Our data demonstrated that residue levels of seven pesticide in pollens/hive may not adversely affect honey bees, but long term exclusive ingestion of the maximal residue levels of imidacloprid (912 ppb) and sulfoxaflor (3 ppm a.i.) may induce substantial bee mortality. Rotating with other insecticides is a necessary and practical way to reduce the residue level of any given pesticide.

  19. 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.

  20. Efficient decoration of nanoparticles intended for intracellular drug targeting with targeting residues, as revealed by a new indirect analytical approach.

    Science.gov (United States)

    Kaplun, Veronika; Stepensky, David

    2014-08-04

    In our previous studies, we developed a nanodrug delivery system (nano-DDS) based on poly(lactic-co-glycolic acid) PLGA nanoparticles encapsulating antigenic peptide and fluorescent marker and 3-stage approach for its decoration with peptide targeting residues. The objectives of this study were (a) to develop methods for quantitative analysis of efficiency of individual conjugation steps and (b) to determine, based on these methods, the efficiency of our 3-stage approach of nano-DDS decoration. We prepared antigenic peptide-loaded PLGA-based nano-DDSs and sequentially decorated them with specific residues using carbodiimide and Click (azide-alkyne Huisgen cycloaddition using copper(I) catalysis) reactions. The extent of cargo encapsulation and release kinetics were analyzed using HPLC-based and colorimetric analytical methods. The efficiency of residue conjugation to the nano-DDSs was analyzed using FTIR spectroscopy and by quantifying the unreacted residues in the reaction mixture (i.e., by indirect analysis of reaction efficiencies). We revealed that copper, the catalyst of the Click reactions, formed complexes with unreacted targeting residues and interfered with the analysis of their conjugation efficiency. We used penicillamine (a chelator) to disrupt these complexes, and to recover the unreacted residues. Quantitative analysis revealed that 28,800-34,000 targeting residues (corresponding to 11-13 nm(2) surface area per residue) had been conjugated to a single nano-DDS using our 3-stage decoration approach, which is much higher than previously reported conjugation efficiencies. We conclude that the applied analytical tools allow quantitative analysis of nano-DDSs and the efficiency of their conjugation with targeting residues. The 3-stage decoration approach resulted in dense conjugation of nano-DDSs with targeting residues. The present decoration and analytical approaches can be effectively applied to other types of delivery systems and other targeting

  1. Dietary exposure to tetracycline residues through milk consumption in Iran

    OpenAIRE

    Aalipour, Fathollah; Mirlohi, Maryam; Jalali, Mohammad; Azadbakht, Leila

    2015-01-01

    Background The abundant use of tetracycline antibiotics in veterinary medicine may result in the presence of their residues in milk at unsafe concentrations that can adversely affect public health. The aim of the current study was to evaluate the risk of tetracycline residue (TET) intake via milk consumption amongst different age groups of human consumers in Iran. Methods To quantify the drug residues, HPLC analysis was performed under isocratic conditions using UV detection at 355?nm. Milk c...

  2. Wide-Scope Screening Method for Multiclass Veterinary Drug Residues in Fish, Shrimp, and Eel Using Liquid Chromatography-Quadrupole High-Resolution Mass Spectrometry.

    Science.gov (United States)

    Turnipseed, Sherri B; Storey, Joseph M; Lohne, Jack J; Andersen, Wendy C; Burger, Robert; Johnson, Aaron S; Madson, Mark R

    2017-08-30

    A screening method for veterinary drug residues in fish, shrimp, and eel using LC with a high-resolution MS instrument has been developed and validated. The method was optimized for over 70 test compounds representing a variety of veterinary drug classes. Tissues were extracted by vortex mixing with acetonitrile acidified with 2% acetic acid and 0.2% p-toluenesulfonic acid. A centrifuged portion of the extract was passed through a novel solid phase extraction cartridge designed to remove interfering matrix components from tissue extracts. The eluent was then evaporated and reconstituted for analysis. Data were collected with a quadrupole-Orbitrap high-resolution mass spectrometer using both nontargeted and targeted acquisition methods. Residues were detected on the basis of the exact mass of the precursor and a product ion along with isotope pattern and retention time matching. Semiquantitative data analysis compared MS 1 signal to a one-point extracted matrix standard at a target testing level. The test compounds were detected and identified in salmon, tilapia, catfish, shrimp, and eel extracts fortified at the target testing levels. Fish dosed with selected analytes and aquaculture samples previously found to contain residues were also analyzed. The screening method can be expanded to monitor for an additional >260 veterinary drugs on the basis of exact mass measurements and retention times.

  3. 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 children children with tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  4. Determination of the Residual Anthracene Concentration in Cultures of Haloalkalitolerant Actinomycetes by Excitation Fluorescence, Emission Fluorescence, and Synchronous Fluorescence: Comparative Study

    Directory of Open Access Journals (Sweden)

    Reyna del Carmen Lara-Severino

    2016-01-01

    Full Text Available Polycyclic aromatic hydrocarbons (PAHs are compounds that can be quantified by fluorescence due to their high quantum yield. Haloalkalitolerant bacteria tolerate wide concentration ranges of NaCl and pH. They are potentially useful in the PAHs bioremediation of saline environments. However, it is known that salinity of the sample affects fluorescence signal regardless of the method. The objective of this work was to carry out a comparative study based on the sensitivity, linearity, and detection limits of the excitation, emission, and synchronous fluorescence methods, during the quantification of the residual anthracene concentration from the following haloalkalitolerant actinomycetes cultures Kocuria rosea, Kocuria palustris, Microbacterium testaceum, and 4 strains of Nocardia farcinica, in order to establish the proper fluorescence method to study the PAHs biodegrading capacity of haloalkalitolerant actinobacteria. The study demonstrated statistical differences among the strains and among the fluorescence methods regarding the anthracene residual concentration. The results showed that excitation and emission fluorescence methods performed very similarly but sensitivity in excitation fluorescence is slightly higher. Synchronous fluorescence using Δλ=150 nm is not the most convenient method. Therefore we propose the excitation fluorescence as the fluorescence method to be used in the study of the PAHs biodegrading capacity of haloalkalitolerant actinomycetes.

  5. Further studies on the use of enzyme profiles to monitor residue accumulation in wildlife: Plasma enzymes in starlings fed graded concentrations of morsodren, DDE, Aroclor 1254, and malathion

    Science.gov (United States)

    Dieter, M.P.

    1975-01-01

    Wild-trapped starlings (Sturnus vulgaris) were fed concentrations of Morsodren (2, 4, and 8 ppm), DDE or Aroclor 1254 (5, 25, and 100 ppm), or malathion (8, 35, and 160 ppm) that were found to be sublethal in pen-reared Coturnix quail fed these amounts for 12 weeks. Plasma enzymes had to be measured earlier than planned in starlings fed Morsodren (at three weeks) or the organochlorine compounds (at seven weeks) because of unexpected, subsequent mortality. Variations in enzyme response were greater in wild than in pen-reared birds, but not enough to mask the toxicant-induced changes in enzyme activity. Cholinesterase activities decreased in birds fed Morsodren or malathion, and increased in those fed the organochlorine compounds. Lactate dehydrogenase activities increased two-fold in starlings fed Morsodren and two- to four-fold in those fed the organochlorine compounds, but only 50% in those fed malathion. Further examination of enzyme profiles showed that creatine kinase and aspartate aminotransferase activities increased two-to four-fold in birds fed Morsodren or the organochlorine compounds but not at all in those fed malathion. Thus the classes of environmental contaminants fed to starlings could be easily distinguished by these enzymatic parameters. Evaluation of enzymatic profiles appears to be a potentially valuable technique to monitor the presence of toxicants in wild populations, especially if used to complement standard chemical residue analyses. Here the residue analyses showed, after three weeks feeding, that mercury in the carcasses reflected the concentrations fed daily, whereas accumulation in the livers was two- to four-fold greater. After seven weeks feeding, liver residues of either organochlorine compound were about three-fold higher than the concentrations fed daily. However, four times as much DDE as Aroclor 1254 had accumulated in the carcasses.

  6. Residual radionuclide concentrations and estimated radiation doses at the former French nuclear weapons test sites in Algeria.

    Science.gov (United States)

    Danesi, P R; Moreno, J; Makarewicz, M; Louvat, D

    2008-11-01

    In order to assess the level of residual radioactivity and evaluate the radiological conditions at the former French nuclear testing sites of Reggane and Taourirt Tan Afella in the south of Algeria, the International Atomic Energy Agency, at the request of the government of Algeria, conducted a field mission to the sites in 1999. At these locations, France conducted a number of nuclear tests in the early 1960s. At the ground zero locality of the ''Gerboise Blanche'' atmospheric test (Reggane) and in the vicinity of a tunnel where radioactive lava was ejected during a poorly contained explosion (Taourirt Tan Afella), non-negligible levels of radioactive material could still be measured. Using the information collected and using realistic potential exposure scenarios, radiation doses to potential occupants and visitors to the sites were estimated.

  7. Longitudinal community plasma HIV-1 RNA concentrations and incidence of HIV-1 among injecting drug users: prospective cohort study

    OpenAIRE

    Wood, Evan; Kerr, Thomas; Marshall, Brandon D L; Li, Kathy; Zhang, Ruth; Hogg, Robert S; Harrigan, P Richard; Montaner, Julio S G

    2009-01-01

    Objective To examine the relation between plasma HIV-1 RNA concentrations in the community and HIV incidence among injecting drug users. Design Prospective cohort study. Setting Inner city community in Vancouver, Canada. Participants Injecting drug users, with and without HIV, followed up every six months between 1 May 1996 and 30 June 2007. Main outcome measures Estimated community plasma HIV-1 RNA in the six months before each HIV negative participant?s follow-up visit. Associated HIV incid...

  8. Pesticide residue concentration in soil following conventional and Low-Input Crop Management in a Mediterranean agro-ecosystem, in Central Greece

    Energy Technology Data Exchange (ETDEWEB)

    Karasali, Helen, E-mail: e.karassali@bpi.gr [Laboratory of Chemical Control of Pesticides, Department of Pesticides Control and Phytopharmacy, Benaki Phytopathological Institute, 8 St. Delta Street, Kifissia, 14561 Athens (Greece); Marousopoulou, Anna [Laboratory of Chemical Control of Pesticides, Department of Pesticides Control and Phytopharmacy, Benaki Phytopathological Institute, 8 St. Delta Street, Kifissia, 14561 Athens (Greece); Machera, Kyriaki, E-mail: k.machera@bpi.gr [Laboratory of Pesticides Toxicology, Department of Pesticides Control and Phytopharmacy, Benaki Phytopathological Institute, 8 St. Delta Street, Kifissia, 14561 Athens (Greece)

    2016-01-15

    The present study was focused on the comparative evaluation of pesticide residues, determined in soil samples from Kopaida region, Greece before and after the implementation of Low-Input Crop Management (LCM) protocols. LCM has been suggested as an environmental friendly plant protection approach to be applied on crops growing in vulnerable to pollution ecosystems, with special focus on the site specific problems. In the case of the specific pilot area, the vulnerability was mainly related to the pollution of water bodies from agrochemicals attributed to diffuse pollution primarily from herbicides and secondarily from insecticides. A total of sixty-six soil samples, were collected and analyzed during a three-year monitoring study and the results of the determined pesticide residues were considered for the impact evaluation of applied plant protection methodology. The LCM was developed and applied in the main crops growing in the pilot area i.e. cotton, maize and industrial tomato. Herbicides active ingredients such as ethalfluralin, trifluralin, pendimethalin, S-metolachlor and fluometuron were detected in most samples at various concentrations. Ethalfluralin, which was the active ingredient present in the majority of the samples ranged from 0.01 μg g{sup −1} to 0.26 μg g{sup −1} soil dry weight. However, the amount of herbicides measured after the implementation of LCM for two cropping periods, was reduced by more than 75% in all cases. The method of analysis was based on the simultaneous extraction of the target compounds by mechanical shaking, followed by liquid chromatography mass spectrometric and gas chromatography electron capture (LC–MS/MS and GC–ECD) analysis. - Highlights: • Effect of Low Input Crop Management (LCM) in a vulnerable to pollution ecosystem. • LCM resulted in herbicide residues reduction in the range of 75 and 100% in all cases. • Conventional practices resulted in increased herbicide residues up to 18%. • Anthropogenic

  9. Real-time amplification of HLA-DQA1 for counting residual white blood cells in filtered platelet concentrates

    NARCIS (Netherlands)

    Mohammadi, Tamimount; Reesink, Henk W.; Vandenbroucke-Grauls, Christina M. J. E.; Savelkoul, Paul H. M.

    2004-01-01

    BACKGROUND A real-time polymerase chain reaction (PCR) assay based on amplification of a conserved region of the HLA-DQA1 locus was developed and validated to assess its suitability in quantitating low levels of white blood cells (WBCs) in filtered platelet (PLT) concentrates (PCs). STUDY DESIGN AND

  10. Enhanced primary treatment of concentrated black water and kitchen residues within DESAR concept using two types of anaerobic digesters

    NARCIS (Netherlands)

    Kujawa-Roeleveld, K.; Elmitwalli, T.A.; Zeeman, G.

    2006-01-01

    Anaerobic digestion of concentrated domestic wastewater streams - black or brown water, and solid fraction of kitchen waste is considered as a core technology in a source separation based sanitation concept (DESAR - decentralised sanitation and reuse). A simple anaerobic digester can be implemented

  11. Effect of leaching residual methyl methacrylate concentrations on in vitro cytotoxicity of heat polymerized denture base acrylic resin processed with different polymerization cycles.

    Science.gov (United States)

    Bural, Canan; Aktaş, Esin; Deniz, Günnur; Ünlüçerçi, Yeşim; Bayraktar, Gülsen

    2011-08-01

    Residual methyl methacrylate (MMA) may leach from the acrylic resin denture bases and have adverse effects on the oral mucosa. This in vitro study evaluated and correlated the effect of the leaching residual MMA concentrations ([MMA]r) on in vitro cytotoxicity of L-929 fibroblasts. A total of 144 heat-polymerized acrylic resin specimens were fabricated using 4 different polymerization cycles: (1) at 74ºC for 9 h, (2) at 74ºC for 9 h and terminal boiling (at 100ºC) for 30 min, (3) at 74ºC for 9 h and terminal boiling for 3 h, (4) at 74ºC for 30 min and terminal boiling for 30 min. Specimens were eluted in a complete cell culture medium at 37ºC for 1, 2, 5 and 7 days. [MMA]r in eluates was measured using high-performance liquid chromatography. In vitro cytotoxicity of eluates on L-929 fibroblasts was evaluated by means of cell proliferation using a tetrazolium salt XTT (sodium 3´-[1-phenyl-aminocarbonyl)-3,4-tetrazolium]bis(4-methoxy-6-nitro)benzenesulphonic acid) assay. Differences in [MMA]r of eluates and cell proliferation values between polymerization cycles were statistically analyzed by Kruskal-Wallis, Friedman and Dunn's multiple comparison tests. The correlation between [MMA]r of eluates and cell proliferation was analyzed by Pearson's correlation test (p<0.05). [MMA]r was significantly (p<0.001) higher in eluates of specimens polymerized with cycle without terminal boiling after elution of 1 and 2 days. Cell proliferation values for all cycles were significantly (p<0.01) lower in eluates of 1 day than those of 2 days. The correlation between [MMA]r and cell proliferation values was negative after all elution periods, showing significance (p<0.05) for elution of 1 and 2 days. MMA continued to leach from acrylic resin throughout 7 days and leaching concentrations markedly reduced after elution of 1 and 2 days. Due to reduction of leaching residual MMA concentrations, use of terminal boiling in the polymerization process for at least 30 min and water

  12. Effect of leaching residual methyl methacrylate concentrations on in vitro cytotoxicity of heat polymerized denture base acrylic resin processed with different polymerization cycles

    Directory of Open Access Journals (Sweden)

    Canan Bural

    2011-08-01

    Full Text Available OBJECTIVES: Residual methyl methacrylate (MMA may leach from the acrylic resin denture bases and have adverse effects on the oral mucosa. This in vitro study evaluated and correlated the effect of the leaching residual MMA concentrations ([MMA]r on in vitro cytotoxicity of L-929 fibroblasts. MATERIAL AND METHODS: A total of 144 heat-polymerized acrylic resin specimens were fabricated using 4 different polymerization cycles: (1 at 74ºC for 9 h, (2 at 74ºC for 9 h and terminal boiling (at 100ºC for 30 min, (3 at 74ºC for 9 h and terminal boiling for 3 h, (4 at 74ºC for 30 min and terminal boiling for 30 min. Specimens were eluted in a complete cell culture medium at 37ºC for 1, 2, 5 and 7 days. [MMA]r in eluates was measured using high-performance liquid chromatography. In vitro cytotoxicity of eluates on L-929 fibroblasts was evaluated by means of cell proliferation using a tetrazolium salt XTT (sodium 3´-[1-phenyl-aminocarbonyl-3,4-tetrazolium]bis(4-methoxy-6-nitrobenzenesulphonic acid assay. Differences in [MMA]r of eluates and cell proliferation values between polymerization cycles were statistically analyzed by Kruskal-Wallis, Friedman and Dunn's multiple comparison tests. The correlation between [MMA]r of eluates and cell proliferation was analyzed by Pearson's correlation test (p<0.05. RESULTS: [MMA]r was significantly (p<0.001 higher in eluates of specimens polymerized with cycle without terminal boiling after elution of 1 and 2 days. Cell proliferation values for all cycles were significantly (p<0.01 lower in eluates of 1 day than those of 2 days. The correlation between [MMA]r and cell proliferation values was negative after all elution periods, showing significance (p<0.05 for elution of 1 and 2 days. MMA continued to leach from acrylic resin throughout 7 days and leaching concentrations markedly reduced after elution of 1 and 2 days. CONCLUSION: Due to reduction of leaching residual MMA concentrations, use of terminal boiling in

  13. Driving under the influence of drugs in Sweden with zero concentration limits in blood for controlled substances.

    Science.gov (United States)

    Jones, Alan Wayne

    2005-12-01

    This article describes the background and implementation in Sweden of zero-concentration limits for controlled drugs in the blood of drivers. Eliminating the need to prove that a person's ability to drive safely was impaired by drugs has greatly simplified the prosecution case, which now rests primarily on the forensic toxicology report. Driving under the influence of a prescription drug listed as a controlled substance is exempt from the zero-limit law provided the medication was being used in accordance with a physician's direction and the person was not considered unfit to drive. The prevalence of driving under the influence of drugs (DUID) in Sweden was evaluated from police reports with the main focus on the toxicological findings. A large case series of DUID suspects was compared before and after introducing zero concentration limits in blood for controlled substances on July 1, 1999. The spectrum of drugs used by typical offenders and the concentrations of various licit and illicit substances in blood were evaluated and compared. Immediately after the zero-limit law came into force, the number of cases of DUID submitted by the police for toxicological analysis increased sharply and is currently ten-fold higher than before the new legislation. Statistics show that about 85% of all blood samples sent for toxicological analysis have one or more banned substances present. Amphetamine is by far the leading drug of abuse in Sweden and was identified in about 50-60% of all DUID suspects either alone or together with other controlled substances. The next most frequently encountered illicit drug was tetrahydrocannabinol (THC), with positive findings in about 20-25% of cases. Various prescription drugs, mainly sedative-hypnotics like diazepam and flunitrazepam, were also highly prevalent and these occurred mostly together with illicit substances. Opiates, such as 6-acetyl morphine and morphine, the metabolites of heroin, were high on the list of substances identified

  14. Construction of a predictive model for concentration of nickel and vanadium in vacuum residues of crude oils using artificial neural networks and LIBS.

    Science.gov (United States)

    Tarazona, José L; Guerrero, Jáder; Cabanzo, Rafael; Mejía-Ospino, E

    2012-03-01

    A predictive model to determine the concentration of nickel and vanadium in vacuum residues of Colombian crude oils using laser-induced breakdown spectroscopy (LIBS) and artificial neural networks (ANNs) with nodes distributed in multiple layers (multilayer perceptron) is presented. ANN inputs are intensity values in the vicinity of the emission lines 300.248, 301.200 and 305.081 nm of the Ni(I), and 309.310, 310.229, and 311.070 nm of the V(II). The effects of varying number of nodes and the initial weights and biases in the ANNs were systematically explored. Average relative error of calibration/prediction (REC/REP) and average relative standard deviation (RSD) metrics were used to evaluate the performance of the ANN in the prediction of concentrations of two elements studied here. © 2012 Optical Society of America

  15. Per-residue energy decomposition pharmacophore model to enhance virtual screening in drug discovery: a study for identification of reverse transcriptase inhibitors as potential anti-HIV agents

    Directory of Open Access Journals (Sweden)

    Cele FN

    2016-04-01

    Full Text Available Favourite N Cele, Muthusamy Ramesh, Mahmoud ES Soliman Molecular Modelling and Drug Design Research Group, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa Abstract: A novel virtual screening approach is implemented herein, which is a further improvement of our previously published “target-bound pharmacophore modeling approach”. The generated pharmacophore library is based only on highly contributing amino acid residues, instead of arbitrary pharmacophores, which are most commonly used in the conventional approaches in literature. Highly contributing amino acid residues were distinguished based on free binding energy contributions obtained from calculation from molecular dynamic (MD simulations. To the best of our knowledge; this is the first attempt in the literature using such an approach; previous approaches have relied on the docking score to generate energy-based pharmacophore models. However, docking scores are reportedly unreliable. Thus, we present a model for a per-residue energy decomposition, constructed from MD simulation ensembles generating a more trustworthy pharmacophore model, which can be applied in drug discovery workflow. This work is aimed at introducing a more rational approach to the field of drug design, rather than comparing the validity of this approach against those previously reported. We recommend additional computational and experimental work to further validate this approach. This approach was used to screen for potential reverse transcriptase inhibitors using the pharmacophoric features of compound GSK952. The complex was subjected to docking, thereafter, MD simulation confirmed the stability of the system. Experimentally determined inhibitors with known HIV-reverse transcriptase inhibitory activity were used to validate the protocol. Two potential hits (ZINC46849657 and ZINC54359621 showed a significant potential with regard to free binding energy. Reported results obtained from

  16. A multi-residue method for 17 anticoccidial drugs and ractopamine in animal tissues by liquid chromatography-tandem mass spectrometry and time-of-flight mass spectrometry.

    Science.gov (United States)

    Matus, Johanna L; Boison, Joe O

    2016-05-01

    A new and sensitive multi-residue liquid chromatography-tandem mass spectrometry (LC-MS/MS) and liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QToF-MS) method was developed and validated for the determination and confirmation of residues of 17 anticoccidials, plus free ractopamine in poultry muscle and liver, and bovine muscle, liver, and kidney tissues. The 17 anticoccidials are lasalocid, halofuginone, narasin, monensin, semduramicin, ethopabate, robenidine, buquinolate, toltrazuril as its sulfone metabolite, maduramicin, salinomycin, diclazuril, amprolium, decoquinate, dinitolmide, clopidol, and the nicarbazin metabolite DNC (N,N1-bis(4-nitrophenyl)urea). The analytes were extracted and cleaned up within a 3-hour period by simply extracting the analytes into a solvent mixture with salts followed by centrifugation, dilution, and filtration. The validated method was used in a pilot study for the analysis of 173 samples that included quail liver, bovine kidney, liver, muscle, and horse muscle. The predominant residues found in this study were monensin, ractopamine, and lasalocid. The results of this pilot study showed that this new method is applicable to real samples, and is fit for use in a regulatory testing programme. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd. © 2016 Her Majesty the Queen in Right of Canada. Drug Testing and Analysis. © 2016 John Wiley & Sons, Ltd.

  17. Analysis of Veterinary Drug and Pesticide Residues Using the Ethyl Acetate Multiclass/Multiresidue Method in Milk by Liquid Chromatography-Tandem Mass Spectrometry

    Directory of Open Access Journals (Sweden)

    Husniye Imamoglu

    2016-01-01

    Full Text Available A rapid and simple multiclass, ethyl acetate (EtOAc multiresidue method based on liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS detection was developed for the determination and quantification of 26 veterinary drugs and 187 total pesticide residues in milk. Sample preparation was a simple procedure based on liquid–liquid extraction with ethyl acetate containing 0.1% acetic acid, followed by centrifugation and evaporation of the supernatant. The residue was dissolved in ethyl acetate with 0.1% acetic acid and centrifuged prior to LC-MS/MS analysis. Chromatographic separation of analytes was performed on an Inertsil X-Terra C18 column with acetic acid in methanol and water gradient. The repeatability and reproducibility were in the range of 2 to 13% and 6 to 16%, respectively. The average recoveries ranged from 75 to 120% with the RSD (n=18. The developed method was validated according to the criteria set in Commission Decision 2002/657/EC and SANTE/11945/2015. The validated methodology represents a fast and cheap alternative for the simultaneous analysis of veterinary drug and pesticide residues which can be easily extended to other compounds and matrices.

  18. 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.

  19. Standard drug concentrations and smart-pump technology reduce continuous-medication-infusion errors in pediatric patients.

    Science.gov (United States)

    Larsen, Gitte Y; Parker, Howard B; Cash, Jared; O'Connell, Mary; Grant, MaryJo C

    2005-07-01

    To determine if combining standard drug concentrations with "smart-pump" technology reduces reported medication-infusion errors. Preintervention and postintervention comparison of reported medication errors related to infusion therapies during the calendar years 2002 and 2003. A 242-bed university-affiliated tertiary pediatric hospital. Change in continuous-medication-infusion process, comprising the adoption of (1) standard drug concentrations, (2) "smart" syringe pumps, and (3) human-engineered medication labels. Comparison of reported continuous-medication-infusion errors before and after the intervention. The number of reported errors dropped by 73% for an absolute risk reduction of 3.1 to 0.8 per 1000 doses. Preparation errors that occurred in the pharmacy decreased from 0.66 to 0.16 per 1000 doses; the number of 10-fold errors in dosage decreased from 0.41 to 0.08 per 1000 doses. The use of standard drug concentrations, smart syringe pumps, and user-friendly labels reduces reported errors associated with continuous medication infusions. Standard drug concentrations can be chosen to allow most neonates to receive needed medications without concerns related to excess fluid administration.

  20. Immobilization of β-Cyclodextrin-Conjugated Lactoferrin onto Polymer Monolith for Enrichment of Ga in Metabolic Residues of Ga-Based Anticancer Drugs.

    Science.gov (United States)

    Zheng, Haijiao; Zhu, Tenggao; Li, Xiqian; Wang, Guan; Jia, Qiong

    2017-12-11

    Biological-material-functionalized porous monoliths were prepared with lactoferrin and β-cyclodextrin via a click reaction. With the monolith as an extraction medium, a method combined with ICP-MS was developed for the determination of total gallium originating from metabolic residues of orally bioavailable gallium complexes with tris(8-quinolinolato)gallium (GaQ 3 ) as a representative. The method exhibited favorable adsorption behaviors for gallium with high selectivity, low detection limit (2 ng L -1 ), and an enrichment factor of 29-fold with the sample throughput of 30 min -1 . The developed approach was validated by the analysis of gallium from GaQ 3 metabolic residues in a human cell line. Additionally, the practical applicability of this method was evaluated by the determination of gallium in human blood and urine samples from cancer patients. Results illustrated that the prepared monolith had potential in Ga-based anticancer drug analysis in complex biological samples.

  1. Platinum-based anticancer drugs in waste waters of a major UK hospital and predicted concentrations in recipient surface waters.

    Science.gov (United States)

    Vyas, Nitin; Turner, Andrew; Sewell, Graham

    2014-09-15

    Concentrations of the cytotoxic platinum-based anticancer drugs, as total Pt, have been measured over a three week period in one of the main drains and in the effluent of the oncology ward of a major UK hospital (Derriford, Plymouth). Concentrations of Pt were highly variable in both discharges, and ranged from about 0.02 to 140 μg L(-1) in the oncology effluent and from about 0.03 to 100 μg L(-1) in the main drain. A comparison of drug administration figures over the study period with an estimate of the quantity of Pt discharged through the drains suggests that about 22% of total Pt is emitted to the environment from the hospital with the remainder being discharged by treated patients in the wider community. Administration figures for the three Pt-based drugs used in the hospital (cisplatin, carboplatin and oxaliplatin) coupled with published measurements on the removal of the drugs by conventional sewage treatment allowed the concentrations of Pt arising from each drug to be predicted in recipient surface waters as a function of water flow rate. For conditions representative of the region under study, concentrations of total Pt between a few tens and in excess of 100 pg L(-1) are predicted, with the principal form of the metal occurring as carboplatin and its metabolites. Although predicted concentrations are below EMEA guidelines warranting further risk assessment, the presence of substances in surface waters that are potentially carcinogenic, mutagenic and teratogenic and yet whose environmental effects are not understood is cause for concern. Copyright © 2014 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

    Sindrup, Søren H; Holbech, Jakob V; 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 polyneur......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.......4 (95% CI -0.9: 0.1) by pregabalin and -1.6 (95% CI-2.1:-1.1) by combination therapy. On monotherapy, there was no difference between responders and non-responders with respect to concentrations of imipramine (mean 161 nmol/L vs. 229 nmol/L, P=0.129) and pregabalin (mean 9.8 μmol/L vs. 11.7 μmol/L, P=0...... for mono-therapy nor for combination therapy (P=0.161-0.797). Isobulographic presentations of reponders with imipramine and pregabalin concentrations during combination therapy did not indicate synergistic interaction. DISCUSSION: There were no important relations between drug concentrations and efficacy...

  3. Membrane distillation as an online concentration technique: application to the determination of pharmaceutical residues in natural waters.

    Science.gov (United States)

    Gethard, Ken; Mitra, Somenath

    2011-04-01

    Membrane distillation (MD) is presented for the first time as a real-time, online concentration technique, where the aqueous matrix is removed from the sample to enhance analyte enrichment. Therefore, MD is a universal method for a wide range of compounds and is unlike conventional membrane extractions that rely on the permeation of the solute into an extractant phase. The MD process showed excellent precision with relative standard deviation between 3% and 5%, linear calibration, and the detection limits for pharmaceutical compounds in the range of 0.01 to 20 mg L(-1) by HPLC-UV analysis. The temperature and flow rate of the feed solution were found to be important variables.

  4. A simulation model for the prediction of tissue:plasma partition coefficients for drug residues in natural casings.

    NARCIS (Netherlands)

    Haritova, A.M.; Fink-Gremmels, J.

    2010-01-01

    Tissue residues arise from the exposure of animals to undesirable substances in animal feed materials and drinking water and to the therapeutic or zootechnical use of veterinary medicinal products. In the framework of this study, an advanced toxicokinetic model was developed to predict the

  5. 76 FR 16290 - Tolerances for Residues of New Animal Drugs in Food; 2-Acetylamino-5-Nitrothiazole; Buquinolate...

    Science.gov (United States)

    2011-03-23

    ... reference an approved combination drug injectable solution containing florfenicol and flunixin (75 FR 1274...; Buquinolate; Chlorobutanol; Estradiol and Related Esters; Ethylenediamine; Florfenicol; Flunixin; Furazolidone... approval of an FAP for a combination drug, antibiotic/steroid intramammary infusion (28 FR 4948, May 17...

  6. Uncovering the local inelastic interactions during manufacture of ductile cast iron: How the substructure of the graphite particles can induce residual stress concentrations in the matrix

    Science.gov (United States)

    Andriollo, Tito; Hellström, Kristina; Sonne, Mads Rostgaard; Thorborg, Jesper; Tiedje, Niels; Hattel, Jesper

    2018-02-01

    Recent X-ray diffraction (XRD) measurements have revealed that plastic deformation and a residual elastic strain field can be present around the graphite particles in ductile cast iron after manufacturing, probably due to some local mismatch in thermal contraction. However, as only one component of the elastic strain tensor could be obtained from the XRD data, the shape and magnitude of the associated residual stress field have remained unknown. To compensate for this and to provide theoretical insight into this unexplored topic, a combined experimental-numerical approach is presented in this paper. First, a material equivalent to the ductile cast iron matrix is manufactured and subjected to dilatometric and high-temperature tensile tests. Subsequently, a two-scale hierarchical top-down model is devised, calibrated on the basis of the collected data and used to simulate the interaction between the graphite particles and the matrix during manufacturing of the industrial part considered in the XRD study. The model indicates that, besides the viscoplastic deformation of the matrix, the effect of the inelastic deformation of the graphite has to be considered to explain the magnitude of the XRD strain. Moreover, the model shows that the large elastic strain perturbations recorded with XRD close to the graphite-matrix interface are not artifacts due to e.g. sharp gradients in chemical composition, but correspond to residual stress concentrations induced by the conical sectors forming the internal structure of the graphite particles. In contrast to common belief, these results thus suggest that ductile cast iron parts cannot be considered, in general, as stress-free at the microstructural scale.

  7. Enhanced primary treatment of concentrated black water and kitchen residues within DESAR concept using two types of anaerobic digesters.

    Science.gov (United States)

    Kujawa-Roeleveld, K; Elmitwalli, T; Zeeman, G

    2006-01-01

    Anaerobic digestion of concentrated domestic wastewater streams--black or brown water, and solid fraction of kitchen waste is considered as a core technology in a source separation based sanitation concept (DESAR--decentralised sanitation and reuse). A simple anaerobic digester can be implemented for an enhanced primary treatment or, in some situations, as a main treatment. Two reactor configurations were extensively studied; accumulation system (AC) and UASB septic tank at 15, 20 and 25 degrees C. Due to long retention times in an AC reactor, far stabilisation of treated medium can be accomplished with methanisation up to 60%. The AC systems are the most suitable to apply when the volume of waste to be treated is minimal and when a direct reuse of a treated medium in agriculture is possible. Digested effluent contains both liquid and solids. In a UASB septic tank, efficient separation of solids and liquid is accomplished. The total COD removal was above 80% at 25 degrees C. The effluent contains COD and nutrients, mainly in a soluble form. The frequency of excess sludge removal is low and sludge is well stabilised due to a long accumulation time.

  8. Optimization of elution salt concentration in stepwise elution of protein chromatography using linear gradient elution data. Reducing residual protein A by cation-exchange chromatography in monoclonal antibody purification.

    Science.gov (United States)

    Ishihara, Takashi; Kadoya, Toshihiko; Endo, Naomi; Yamamoto, Shuichi

    2006-05-05

    Our simple method for optimization of the elution salt concentration in stepwise elution was applied to the actual protein separation system, which involves several difficulties such as detection of the target. As a model separation system, reducing residual protein A by cation-exchange chromatography in human monoclonal antibody (hMab) purification was chosen. We carried out linear gradient elution experiments and obtained the data for the peak salt concentration of hMab and residual protein A, respectively. An enzyme-linked immunosorbent assay was applied to the measurement of the residual protein A. From these data, we calculated the distribution coefficient of the hMab and the residual protein A as a function of salt concentration. The optimal salt concentration of stepwise elution to reduce the residual protein A from the hMab was determined based on the relationship between the distribution coefficient and the salt concentration. Using the optimized condition, we successfully performed the separation, resulting in high recovery of hMab and the elimination of residual protein A.

  9. Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells.

    Science.gov (United States)

    Cilião, H L; Ribeiro, D L; Camargo-Godoy, R B O; Specian, A F L; Serpeloni, J M; Cólus, I M S

    2015-02-01

    Immunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MTT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3h of exposure and with concentrations of 675 and 1520 ng/ml after 24h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. The role of bicarbonate in platelet additive solution for apheresis platelet concentrates stored with low residual plasma.

    Science.gov (United States)

    Radwanski, Katherine; Min, Kyungyoon

    2013-03-01

    Complex platelet additive solutions (PASs) are required to store platelet (PLT) concentrates with plasma levels below 30%. Previously, apheresis PLTs stored with 5% plasma in acetate- and bicarbonate-containing PAS maintained stable pH and bicarbonate levels during 7-day storage. Due to this observation, the necessity of added bicarbonate in PAS was investigated and whether the concurrent increase in PAS pH after bicarbonate addition had any effect on PLT storage. Apheresis PLTs were stored in 5% plasma-95% high- or low-pH PAS, with or without bicarbonate (n=10 per arm). Bicarbonate PAS PLTs were paired and nonbicarbonate PAS PLTs were paired (split from same double-dose collection). PLTs were evaluated for in vitro variables on Days 1 and 7 and up to Day 14 if the Day 7 pH was higher than 6.2. PLT pH was maintained above 7.3 to Day 14 in bicarbonate PAS PLTs while pH failures below 6.2 were observed in 4 of 10 and 2 of 10 units on Day 7 in low- and high-pH nonbicarbonate PAS arms, respectively. Day 7 in vitro variables in nonbicarbonate PAS PLTs with pH values of higher than 6.2 were comparable to Day 7 variables in bicarbonate PAS PLTs. The pH of bicarbonate PAS did have a small effect on pH and bicarbonate levels in PLT units, but did not have an effect on functional variables and metabolism. Bicarbonate was not required to maintain in vitro PLT function in 5% plasma-95% PAS, but was required as a pH buffer and increased PAS pH did not significantly contribute to this effect. © 2012 American Association of Blood Banks.

  11. 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.

  12. Fine mapping the spatial distribution and concentration of unlabeled drugs within tissue micro-compartments using imaging mass spectrometry.

    Directory of Open Access Journals (Sweden)

    Anna Nilsson

    Full Text Available Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 microm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1 and fragmented daughter MS/MS ions (m/z 170.1 and 152.1 were dispersed in a concentration gradient (80 fmol-5 pmol away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention.

  13. 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.

  14. Therapeutic drug monitoring of cerebrospinal fluid vancomycin concentration during intraventricular administration.

    Science.gov (United States)

    Popa, D; Loewenstein, L; Lam, S W; Neuner, E A; Ahrens, C L; Bhimraj, A

    2016-02-01

    Limited data are available on intraventricular vancomycin dosing for meningitis. This study explored clinical characteristics that correlated with cerebrospinal fluid (CSF) concentrations. Over a nine-year period, 13 patients with 34 CSF vancomycin concentrations were evaluated. CSF output and time from dose correlated with CSF vancomycin concentration. No relationship was seen with regards to CSF protein, white blood cell count or glucose. Copyright © 2015. Published by Elsevier Ltd.

  15. Authorization and Toxicity of Veterinary Drugs and Plant Protection Products: Residues of the Active Ingredients in Food and Feed and Toxicity Problems Related to Adjuvants

    Directory of Open Access Journals (Sweden)

    Szandra Klátyik

    2017-09-01

    Full Text Available Chemical substances applied in animal husbandry or veterinary medicine and in crop protection represent substantial environmental loads, and their residues occur in food and feed products. Product approval is governed differently in these two sectors in the European Union (EU, and the occurrence of veterinary drug (VD and pesticide residues indicated by contamination notification cases in the Rapid Alert System for Food and Feed of the EU also show characteristic differences. While the initial high numbers of VD residues reported in 2002 were successfully suppressed to less than 100 cases annually by 2006 and on, the number of notification cases for pesticide residues showed a gradual increase from a low (approximately 50 cases annually initial level until 2005 to more than 250 cases annually after 2009, with a halt occurring only in 2016. Main notifiers of VD residues include Germany, Belgium, the UK, and Italy (63, 59, 42, and 31 notifications announced, respectively, and main consigning countries of non-compliances are Vietnam, India, China, and Brazil (88, 50, 34, and 23 notifications, respectively. Thus, countries of South and Southeast Asia are considered a vulnerable point with regard to VD residues entering the EU market. Unintended side effects of VDs and plant protection products may be caused not only by the active ingredients but also by various additives in these preparations. Adjuvants (e.g., surfactants and other co-formulants used in therapeutic agents and feed additives, as well as in pesticide formulations have long been considered as inactive ingredients in the aspects of the required main biological effect of the pharmaceutical or pesticide, and in turn, legal regulations of the approval and marketing of these additives specified significantly less stringent risk assessment requirements, than those specified for the active ingredients. However, numerous studies have shown additive, synergistic, or antagonistic side effects

  16. Authorization and Toxicity of Veterinary Drugs and Plant Protection Products: Residues of the Active Ingredients in Food and Feed and Toxicity Problems Related to Adjuvants.

    Science.gov (United States)

    Klátyik, Szandra; Bohus, Péter; Darvas, Béla; Székács, András

    2017-01-01

    Chemical substances applied in animal husbandry or veterinary medicine and in crop protection represent substantial environmental loads, and their residues occur in food and feed products. Product approval is governed differently in these two sectors in the European Union (EU), and the occurrence of veterinary drug (VD) and pesticide residues indicated by contamination notification cases in the Rapid Alert System for Food and Feed of the EU also show characteristic differences. While the initial high numbers of VD residues reported in 2002 were successfully suppressed to less than 100 cases annually by 2006 and on, the number of notification cases for pesticide residues showed a gradual increase from a low (approximately 50 cases annually) initial level until 2005 to more than 250 cases annually after 2009, with a halt occurring only in 2016. Main notifiers of VD residues include Germany, Belgium, the UK, and Italy (63, 59, 42, and 31 notifications announced, respectively), and main consigning countries of non-compliances are Vietnam, India, China, and Brazil (88, 50, 34, and 23 notifications, respectively). Thus, countries of South and Southeast Asia are considered a vulnerable point with regard to VD residues entering the EU market. Unintended side effects of VDs and plant protection products may be caused not only by the active ingredients but also by various additives in these preparations. Adjuvants (e.g., surfactants) and other co-formulants used in therapeutic agents and feed additives, as well as in pesticide formulations have long been considered as inactive ingredients in the aspects of the required main biological effect of the pharmaceutical or pesticide, and in turn, legal regulations of the approval and marketing of these additives specified significantly less stringent risk assessment requirements, than those specified for the active ingredients. However, numerous studies have shown additive, synergistic, or antagonistic side effects between the

  17. Authorization and Toxicity of Veterinary Drugs and Plant Protection Products: Residues of the Active Ingredients in Food and Feed and Toxicity Problems Related to Adjuvants

    Science.gov (United States)

    Klátyik, Szandra; Bohus, Péter; Darvas, Béla; Székács, András

    2017-01-01

    Chemical substances applied in animal husbandry or veterinary medicine and in crop protection represent substantial environmental loads, and their residues occur in food and feed products. Product approval is governed differently in these two sectors in the European Union (EU), and the occurrence of veterinary drug (VD) and pesticide residues indicated by contamination notification cases in the Rapid Alert System for Food and Feed of the EU also show characteristic differences. While the initial high numbers of VD residues reported in 2002 were successfully suppressed to less than 100 cases annually by 2006 and on, the number of notification cases for pesticide residues showed a gradual increase from a low (approximately 50 cases annually) initial level until 2005 to more than 250 cases annually after 2009, with a halt occurring only in 2016. Main notifiers of VD residues include Germany, Belgium, the UK, and Italy (63, 59, 42, and 31 notifications announced, respectively), and main consigning countries of non-compliances are Vietnam, India, China, and Brazil (88, 50, 34, and 23 notifications, respectively). Thus, countries of South and Southeast Asia are considered a vulnerable point with regard to VD residues entering the EU market. Unintended side effects of VDs and plant protection products may be caused not only by the active ingredients but also by various additives in these preparations. Adjuvants (e.g., surfactants) and other co-formulants used in therapeutic agents and feed additives, as well as in pesticide formulations have long been considered as inactive ingredients in the aspects of the required main biological effect of the pharmaceutical or pesticide, and in turn, legal regulations of the approval and marketing of these additives specified significantly less stringent risk assessment requirements, than those specified for the active ingredients. However, numerous studies have shown additive, synergistic, or antagonistic side effects between the

  18. Residual deposits (residual soil)

    International Nuclear Information System (INIS)

    Khasanov, A.Kh.

    1988-01-01

    Residual soil deposits is accumulation of new formate ore minerals on the earth surface, arise as a result of chemical decomposition of rocks. As is well known, at the hyper genes zone under the influence of different factors (water, carbonic acid, organic acids, oxygen, microorganism activity) passes chemical weathering of rocks. Residual soil deposits forming depends from complex of geologic and climatic factors and also from composition and physical and chemical properties of initial rocks

  19. 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

  20. Measuring plasma paracetamol concentrations in all patients with drug overdose or altered consciousness: Does it change outcome?

    Science.gov (United States)

    Dargan, P; Ladhani, S; Jones, A

    2001-01-01

    Objective—To assess whether measuring plasma paracetamol concentrations in all patients with drug overdose or collapse (altered consciousness) changes outcome. Method—A retrospective survey was performed of all patients attending the Accident and Emergency Department at Guy's Hospital, London over a 12 month period who had plasma paracetamol concentrations measured (it is hospital policy that patients presenting after any drug overdose, or with a collapse/altered consciousness have a plasma paracetamol concentration). Results—A total of 440 patients were identified who had plasma paracetamol concentrations measured, of whom 411 were eligible for the study. Altogether 115 patients presented after a collapse and paracetamol was detected in four of these. A total of 296 patients presented after a drug overdose—136 denied overdose with a paracetamol containing product and paracetamol was not detected in any of these 136 cases. Of the remaining 160 patients who gave a positive history for overdose with paracetamol, 122 presented within 24 hours and 94 had detectable paracetamol values with 16 cases above the treatment line, 12 presented more than 24 hours after ingestion, and 26 presented with a staggered overdose. One patient died as a result of paracetamol overdose. Conclusions—This is the first study in the United Kingdom to evaluate the clinical value of routine paracetamol levels in patients presenting to the emergency department after any overdose or a collapse. Taking blood samples for plasma paracetamol estimation in patients who deny taking paracetamol is of little clinical value. However, there is the potential for missing significant paracetamol poisoning in patients presenting with collapse and so screening with a plasma paracetamol concentration is clinically justified in these patients. Such an approach can only be justified in a country in which paracetamol poisoning is prevalent, such as the United Kingdom. PMID:11354207

  1. Accounting for Genotype-by-Environment Interactions and Residual Genetic Variation in Genomic Selection for Water-Soluble Carbohydrate Concentration in Wheat.

    Science.gov (United States)

    Ovenden, Ben; Milgate, Andrew; Wade, Len J; Rebetzke, Greg J; Holland, James B

    2018-04-16

    Abiotic stress tolerance traits are often complex and recalcitrant targets for conventional breeding improvement in many crop species. This study evaluated the potential of genomic selection to predict water-soluble carbohydrate concentration (WSCC), an important drought tolerance trait, in wheat under field conditions. A panel of 358 varieties and breeding lines constrained for maturity was evaluated under rainfed and irrigated treatments across two locations and two years. Whole-genome marker profiles and factor analytic mixed models were used to generate genomic estimated breeding values (GEBVs) for specific environments and environment groups. Additive genetic variance was smaller than residual genetic variance for WSCC, such that genotypic values were dominated by residual genetic effects rather than additive breeding values. As a result, GEBVs were not accurate predictors of genotypic values of the extant lines, but GEBVs should be reliable selection criteria to choose parents for intermating to produce new populations. The accuracy of GEBVs for untested lines was sufficient to increase predicted genetic gain from genomic selection per unit time compared to phenotypic selection if the breeding cycle is reduced by half by the use of GEBVs in off-season generations. Further, genomic prediction accuracy depended on having phenotypic data from environments with strong correlations with target production environments to build prediction models. By combining high-density marker genotypes, stress-managed field evaluations, and mixed models that model simultaneously covariances among genotypes and covariances of complex trait performance between pairs of environments, we were able to train models with good accuracy to facilitate genetic gain from genomic selection. Copyright © 2018, G3: Genes, Genomes, Genetics.

  2. Pesticide residue concentration in soil following conventional and Low-Input Crop Management in a Mediterranean agro-ecosystem, in Central Greece.

    Science.gov (United States)

    Karasali, Helen; Marousopoulou, Anna; Machera, Kyriaki

    2016-01-15

    The present study was focused on the comparative evaluation of pesticide residues, determined in soil samples from Kopaida region, Greece before and after the implementation of Low-Input Crop Management (LCM) protocols. LCM has been suggested as an environmental friendly plant protection approach to be applied on crops growing in vulnerable to pollution ecosystems, with special focus on the site specific problems. In the case of the specific pilot area, the vulnerability was mainly related to the pollution of water bodies from agrochemicals attributed to diffuse pollution primarily from herbicides and secondarily from insecticides. A total of sixty-six soil samples, were collected and analyzed during a three-year monitoring study and the results of the determined pesticide residues were considered for the impact evaluation of applied plant protection methodology. The LCM was developed and applied in the main crops growing in the pilot area i.e. cotton, maize and industrial tomato. Herbicides active ingredients such as ethalfluralin, trifluralin, pendimethalin, S-metolachlor and fluometuron were detected in most samples at various concentrations. Ethalfluralin, which was the active ingredient present in the majority of the samples ranged from 0.01 μg g(-1) to 0.26 μg g(-1) soil dry weight. However, the amount of herbicides measured after the implementation of LCM for two cropping periods, was reduced by more than 75% in all cases. The method of analysis was based on the simultaneous extraction of the target compounds by mechanical shaking, followed by liquid chromatography mass spectrometric and gas chromatography electron capture (LC-MS/MS and GC-ECD) analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Tetracycline antibiotics transfer from contaminated milk to dairy products and the effect of the skimming step and pasteurisation process on residue concentrations.

    Science.gov (United States)

    Gajda, Anna; Nowacka-Kozak, Ewelina; Gbylik-Sikorska, Malgorzata; Posyniak, Andrzej

    2018-01-01

    The presence of antibiotics in raw milk and milk derivatives poses a threat to human health and can negatively affect the dairy industry. Therefore, the main object of this study was to investigate the transfer of oxytetracycline (OTC), tetracycline (TC), chlortetracycline (CTC) and doxycycline (DC) from raw, experimental milk contaminated with tetracyclines (TCs) to different dairy products: cream, butter, buttermilk, sour milk, whey, curd and cheese. Additionally the effect of the skimming process on TCs concentrations was tested, as well as the influence of low-temperature long-time pasteurisation. The analyses of TCs in milk and dairy products were performed by an LC-MS/MS method. In order to determine TCs residues in dairy products, an analytical method was developed with the same extraction step for all matrices. TCs molecules were inhomogenously distributed between the milk derivative fractions. The highest concentrations were determined in curd and cheese in the ranges 320-482 µg/kg and 280-561 µg/kg, respectively. Low levels of TCs in butter and whey were observed (11.8-41.2 µg/kg). TCs were found in sour milk (66.0-111 µg/kg), cream (85.0-115 µg/kg) and buttermilk (196-221 µg/kg) at much higher levels than in butter and whey, but lower than in curd and cheese. During the skimming process, the highest yield of cream was obtained after the raw milk was held at 2-8°C for 24 h. The differences in concentrations of TCs between whole milk and skimmed milk, expressed as percentages of recovery, were below 19% (recoveries in excess of 81%). The highest content was observed in milk and cream skimmed at 2-8°C. The degradation percentages for TCs during the pasteurisation process (63°C for 30 min) were below 19%.

  4. Sub-therapeutic nevirapine concentration during antiretroviral treatment initiation among children living with HIV: Implications for therapeutic drug monitoring.

    Directory of Open Access Journals (Sweden)

    Bindu Parachalil Gopalan

    Full Text Available Nevirapine, a component of antiretroviral therapy (ART in resource-limited settings, known for auto-induction of metabolism, is initiated at half therapeutic dose until day 14 ('lead-in period', and subsequently escalated to full dose. However, studies have shown that this dosing strategy based on adult studies may not be appropriate in children, given that younger children have higher drug clearance rates. In this prospective cohort study, we studied trough plasma nevirapine levels by high performance liquid chromatography (HPLC at days 7, 14 (lead-in period and 28 (full dose period after ART initiation amongst HIV-1 infected children initiating nevirapine-based ART in southern India. Among the 20 children (50% male, median age 9 years included in the study, sub-therapeutic trough plasma nevirapine concentration (<4μg/ml was seen in 65% (13/20 of children during the lead-in period within two weeks of ART initiation and among 10% of children at 4 weeks during full-dose nevirapine. Adherence was documented as ≥95% in all children by both caregiver self-report and pill count. Median nevirapine concentrations achieved at week 1 was 4.8 μg/ml, significantly lower than 8 μg/ml, the concentration achieved at week 4 (p = 0.034. Virological failure at one year of ART was observed in six children, and was not associated with median nevirapine concentration achieved during week 1, 2 or 4. We conclude that the dose escalation strategy currently practiced among young children living with HIV-1 resulted in significant subtherapeutic nevirapine concentration (≤4μg/ml during the lead-in period. We call for a closer look at pediatric-focused dosing strategies for nevirapine initiation in young children. Further studies to establish age-appropriate threshold nevirapine concentration are warranted in young children to corroborate the role of therapeutic drug monitoring in predicting virological outcome.

  5. 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

  6. 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

  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. 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

  9. Quinine unbound concentration is the best marker for therapeutic drug monitoring.

    Science.gov (United States)

    de Pablos-Martinez, Carlos; Porte, Lydie; Fraissinet, François; Berry, Antoine; Séraissol, Patrick; Lavit, Michel; Chatelut, Etienne; Concordet, Didier; Gandia, Peggy

    2016-10-01

    Quinine monitoring should be based on unbound concentration due to variable unbound fraction in malaria patients. Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.

  10. 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

  11. Polychlorobenzenes and polychlorinated biphenyls in ash and soil from several industrial areas in North Vietnam: residue concentrations, profiles and risk assessment.

    Science.gov (United States)

    Nguyen, Thi Hue; Nguyen, Thi Thu Thuy; Nguyen, Hoang Tung

    2016-04-01

    Polychlorinated benzenes (PCBzs) including penta- and hexachlorobenzene can be unintentionally formed from thermal processes in different industrial activities, and very little information is available on the contamination and emission characteristics of these new persistent organic pollutants from industries in Vietnam. In this study, contamination of PCBzs (including penta- and hexachlorobenzene, named PeCBz and HCB, respectively) and PCBs (including CB-28, 52, 101, 153, 138, 180) in fly ash, bottom ash and soil from combustion processes of waste incineration, metallurgy (steel making and zinc production) and cement production from several provinces in the Northern Vietnam, including Hai Duong, Hanoi, Bac Ninh, Hai Phong and Thai Nguyen, was preliminary investigated. The PCBzs concentrations in fly ash, bottom ash and soil ranged from 2.7 to 100 ng g(-1), from 2.7 to 159 ng g(-1) and from 0.28 to 33.9 ng g(-1), respectively. Relatively high residues of PeCBz in fly ash and bottom ash from municipal waste incinerators in some provinces from the Northern Vietnam were encountered. Total PCBs concentrations ranged from 18.0 to 8260 ng g(-1), from 1.0 to 10600 ng g(-1) and from 14.5 to 130 ng g(-1) for the fly ash, bottom ash and soil, respectively. Daily intakes of PeCBz, HCB and PCBs through soil ingestion and dermal exposure estimated for children ranged 0.33-9.93 (mean 3.14), 0.39-21.1 (mean 4.9) and 6.09-1530 ng/kg bw/day (mean 346), respectively; and these intakes were about 4.7-5.4 times higher than those estimated for adult. The intakes of PeCBz and HCB were relatively low, while those for PCBs exceeded WHO TDI for some samples.

  12. A pharmacodynamic analysis method to determine the relative importance of drug concentration and treatment time on effect.

    Science.gov (United States)

    Millenbaugh, N J; Wientjes, M G; Au, J L

    2000-01-01

    The pharmacodynamics of most drugs follow the empirical relationship, C(n) x T = h, where C is drug concentration, T is exposure time and h is drug exposure constant. The value of n indicates the relative importance of C and T in determining the effect. An n value greater than 1.0 indicates that for two infusions that produce the same C x T, a short infusion that delivers high concentrations over a short duration will produce a greater C(n) x T and therefore a greater effect, compared to a long infusion that delivers lower concentrations. The reverse is true for an n value less than 1.0 and would support the use of a slow infusion. Hence, it is important to determine the n values and whether the n value significantly differs from 1.0. This report describes a three-step method for this purpose. First, we obtained experimental data on the relationship between drug concentration, treatment time and effect, and analyzed the data with a three-dimensional surface response method to obtain the pharmacodynamic model parameters and the magnitude of data variability. The experiments used mitomycin C and two human cancer cell lines, i.e. bladder RT4 and pharynx FaDu cells. The n values obtained from four experiments ranged from 1.04 to 1.16 for FaDu cells and from 1.14 to 1.46 for RT4 cells. The variability in the effect data decreased from 11.9% at 0% effect to 6.14% at 100% effect. Second, these results were used with Monte Carlo simulations to generate 100 concentration-time-effect data sets, which contained randomly and normally distributed data variability comparable to the experimentally observed variability, for each experimentally determined n value. This is analogous to performing 100 experiments under the same experimental conditions. Third, we analyzed the simulated data sets to obtain 100 estimated n values. The frequency with which these estimated n values fell above or below 1.0 indicated the probability that the experimentally determined n value used in the

  13. Drug concentrations in the serum and cerebrospinal fluid of patients treated with norvancomycin after craniotomy.

    Science.gov (United States)

    Wu, Y; Kang, J; Wang, Q

    2017-02-01

    Intracranial infection by gram-positive cocci is commonly found after craniotomy. Norvancomycin was independently developed in China, and had demonstrated therapeutic capability against gram-positive infection. This study investigated the serum and cerebrospinal fluid (CSF) concentrations in patients that received intravenous injection of norvancomycin after craniotomy. Patients with an indwelling catheter in the operational area/ventricle after craniotomy were administered norvancomycin by two approaches: (1) The conventional group consisted of 14 cases that were infused with 0.8 g norvancomycin for 1 h, every 12 h; (2) The continuous administration group consisted of 14 cases that were infused with 0.8 g norvancomycin for 1 h, and then another 0.4 g for 11 h with extended infusion, followed by continuous infusion of 0.4 g norvancomycin for 12 h. Samples of serum and CSF were collected at different time-points to measure norvancomycin levels after administration. In the conventional and continuous administration groups, the peak serum concentrations of norvancomycin were 55.52 ± 26.04 and 59.22 ± 41.88 mg/L, respectively, while those at 24 h were 8.21 ± 6.04 and 8.01 ± 4.17 mg/L, respectively. Meanwhile, peak CSF concentrations were 16.31 ± 11.15 and 8.82 ± 8.91 mg/L, respectively, while those at 24 h were 6.12 ± 2.34 and 6.24 ± 4.38 mg/L, respectively. This preliminary study showed that for the early administration of standard doses of norvancomycin post-neurosurgery, the CSF concentration in both the conventional and continuous administration groups reached or exceeded the 90 % minimum inhibitory concentration (MIC 90 , 2 mg/L) of target bacteria such as methicillin-resistant Staphylococcus aureus (MRSA).

  14. Germline genetic predictors of aromatase inhibitor concentrations, estrogen suppression and drug efficacy and toxicity in breast cancer patients.

    Science.gov (United States)

    Hertz, Daniel L; Henry, N Lynn; Rae, James M

    2017-04-01

    The third-generation aromatase inhibitors (AIs), anastrozole, letrozole and exemestane, are highly effective for the treatment of estrogen receptor-positive breast cancer in postmenopausal women. AIs inhibit the aromatase (CYP19A1)-mediated production of estrogens. Most patients taking AIs achieve undetectable blood estrogen concentrations resulting in drug efficacy with tolerable side effects. However, some patients have suboptimal outcomes, which may be due, in part, to inherited germline genetic variants. This review summarizes published germline genetic associations with AI treatment outcomes including systemic AI concentrations, estrogenic response to AIs, AI treatment efficacy and AI treatment toxicities. Significant associations are highlighted with commentary about prioritization for future validation to identify pharmacogenetic predictors of AI treatment outcomes that can be used to inform personalized treatment decisions in patients with estrogen receptor-positive breast cancer.

  15. Potential life-threatening variations of drug concentrations in intravenous infusion systems: potassium chloride, insulin, and heparin

    Energy Technology Data Exchange (ETDEWEB)

    Bergman, N.; Vellar, I.D.

    1982-09-18

    The investigation of concentrations of active agents in common carrier media for intravenous infusion revealed that potassium chloride tends to form a pool when it is added without mixing to carrier media in glass or polyvinyl chloride (PVC) containers which are already suspended in their functional position with ports pointing downwards. Heparin behaves in a similar fashion when added without mixing to carrier media in PVC containers. Such uneven distribution may expose a patient to potentially dangerous, possibly lethal, concentrations of a drug even when a relatively small amount of it is used. Insulin floats to the top of a Haemaccel container if its contents are not adequately mixed after addition of insulin. The resultant irregularity of insulin dosage may make the management of diabetic ketoacidosis more difficult. It is recommended that the instructions for the adequate mixing of contents should appear on all containers of carrier media for intravenous infusions.

  16. 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...

  17. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance.

    Science.gov (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E

    2013-01-01

    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  18. Prevalence of Plasmodium falciparum Molecular Markers of Antimalarial Drug Resistance in a Residual Malaria Focus Area in Sabah, Malaysia.

    Science.gov (United States)

    Norahmad, Nor Azrina; Mohd Abd Razak, Mohd Ridzuan; Abdullah, Noor Rain; Sastu, Umi Rubiah; Imwong, Mallika; Muniandy, Prem Kumar; Saat, Muhammad Nor Farhan; Muhammad, Amirrudin; Jelip, Jenarun; Tikuson, Moizin; Yusof, Norsalleh; Rundi, Christina; Mudin, Rose Nani; Syed Mohamed, Ami Fazlin

    2016-01-01

    Chloroquine (CQ) and fansidar (sulphadoxine-pyrimethamine, SP) were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT) in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P. falciparum isolates in Kota Marudu located in the north-east coast of Sabah. Mutations on genes associated with CQ (pfcrt and pfmdr1) and SP (pfdhps and pfdhfr) were assessed by PCR amplification and restriction fragment length polymorphism. Mutations on the kelch13 marker (K13) associated with artemisinin resistance were determined by DNA sequencing technique. The assessment of pfmdr1 copy number variation associated with mefloquine resistant was done by real-time PCR technique. A low prevalence (6.9%) was indicated for both pfcrt K76T and pfmdr1 N86Y mutations. All P. falciparum isolates harboured the pfdhps A437G mutation. Prevalence of pfdhfr gene mutations, S108N and I164L, were 100% and 10.3%, respectively. Combining the different resistant markers, only two isolates were conferred to have CQ and SP treatment failure markers as they contained mutant alleles of pfcrt and pfmdr1 together with quintuple pfdhps/pfdhfr mutation (combination of pfdhps A437G+A581G and pfdhfr C59R+S108N+I164L). All P. falciparum isolates carried single copy number of pfmdr1 and wild type K13 marker. This study has demonstrated a low prevalence of CQ and SP resistance alleles in the study area. Continuous monitoring of antimalarial drug efficacy is warranted and the findings provide information for policy makers in ensuring a proper malaria control.

  19. Prevalence of Plasmodium falciparum Molecular Markers of Antimalarial Drug Resistance in a Residual Malaria Focus Area in Sabah, Malaysia.

    Directory of Open Access Journals (Sweden)

    Nor Azrina Norahmad

    Full Text Available Chloroquine (CQ and fansidar (sulphadoxine-pyrimethamine, SP were widely used for treatment of Plasmodium falciparum for several decades in Malaysia prior to the introduction of Artemisinin-based Combination Therapy (ACT in 2008. Our previous study in Kalabakan, located in south-east coast of Sabah showed a high prevalence of resistance to CQ and SP, suggesting the use of the treatment may no longer be effective in the area. This study aimed to provide a baseline data of antimalarial drug resistant markers on P. falciparum isolates in Kota Marudu located in the north-east coast of Sabah. Mutations on genes associated with CQ (pfcrt and pfmdr1 and SP (pfdhps and pfdhfr were assessed by PCR amplification and restriction fragment length polymorphism. Mutations on the kelch13 marker (K13 associated with artemisinin resistance were determined by DNA sequencing technique. The assessment of pfmdr1 copy number variation associated with mefloquine resistant was done by real-time PCR technique. A low prevalence (6.9% was indicated for both pfcrt K76T and pfmdr1 N86Y mutations. All P. falciparum isolates harboured the pfdhps A437G mutation. Prevalence of pfdhfr gene mutations, S108N and I164L, were 100% and 10.3%, respectively. Combining the different resistant markers, only two isolates were conferred to have CQ and SP treatment failure markers as they contained mutant alleles of pfcrt and pfmdr1 together with quintuple pfdhps/pfdhfr mutation (combination of pfdhps A437G+A581G and pfdhfr C59R+S108N+I164L. All P. falciparum isolates carried single copy number of pfmdr1 and wild type K13 marker. This study has demonstrated a low prevalence of CQ and SP resistance alleles in the study area. Continuous monitoring of antimalarial drug efficacy is warranted and the findings provide information for policy makers in ensuring a proper malaria control.

  20. A novel doxorubicin-loaded in situ forming gel based high concentration of phospholipid for intratumoral drug delivery.

    Science.gov (United States)

    Wu, Wenqi; Chen, Hui; Shan, Fengying; Zhou, Jing; Sun, Xun; Zhang, Ling; Gong, Tao

    2014-10-06

    The purpose of this study was to develop a safe and effective drug delivery system for local chemotherapy. A novel injectable in-situ-forming gel system was prepared using small molecule materials, including phospholipids, medium chain triglycerides (MCTs), and ethanol. Thus, this new sustained release system was named PME (first letter of phospholipids, MCT, and ethanol). PME has a well-defined molecule structure, a high degree of safety, and better biocompatible characteristics. It was in sol state with low viscosity in vitro and turned into a solid or semisolid gel in situ after injection. When loaded with doxorubicin (Dox), PME-D (doxorubicin-loaded PME) exhibited notably antitumor efficiency in S180 sarcoma tumors bearing mice after a single intratumoral injection. In vitro, PME-D had remarkable antiproliferative efficacies against MCF-7 breast cancer cells for over 5 days. Moreover, the initial burst effect can hardly be observed from PME system, which was different from many other in-situ-forming gels. The in vivo biodistribution study showed the high Dox concentration in tumors compared with other major organs after PME-D intratumoral administration. The strong signal in tumors was retained for more than 14 days after one single injection. The high concentration of Dox in tumor and long-term retention may explain the superior therapeutic efficacy and reduced side effects. The PME-D in-situ-forming gel system is a promising drug delivery system for local chemotherapy.

  1. Validation of an ultra-high-performance liquid chromatography-tandem mass spectrometry method to quantify illicit drug and pharmaceutical residues in wastewater using accuracy profile approach.

    Science.gov (United States)

    Hubert, Cécile; Roosen, Martin; Levi, Yves; Karolak, Sara

    2017-06-02

    The analysis of biomarkers in wastewater has become a common approach to assess community behavior. This method is an interesting way to estimate illicit drug consumption in a given population: by using a back calculation method, it is therefore possible to quantify the amount of a specific drug used in a community and to assess the consumption variation at different times and locations. Such a method needs reliable analytical data since the determination of a concentration in the ngL -1 range in a complex matrix is difficult and not easily reproducible. The best analytical method is liquid chromatography - mass spectrometry coupling after solid-phase extraction or on-line pre-concentration. Quality criteria are not specially defined for this kind of determination. In this context, it was decided to develop an UHPLC-MS/MS method to analyze 10 illicit drugs and pharmaceuticals in wastewater treatment plant influent or effluent using a pre-concentration on-line system. A validation process was then carried out using the accuracy profile concept as an innovative tool to estimate the probability of getting prospective results within specified acceptance limits. Influent and effluent samples were spiked with known amounts of the 10 compounds and analyzed three times a day for three days in order to estimate intra-day and inter-day variations. The matrix effect was estimated for each compound. The developed method can provide at least 80% of results within ±25% limits except for compounds that are degraded in influent. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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.

  3. Simultaneous analysis of aminoglycosides with many other classes of drug residues in bovine tissues by ultrahigh-performance liquid chromatography-tandem mass spectrometry using an ion-pairing reagent added to final extracts

    Science.gov (United States)

    The way to maximize scope of analysis, sample throughput, and laboratory efficiency in the monitoring of veterinary drug residues in food animals is to determine as many analytes as possible as fast as possible in as few methods as possible. Capital and overhead expenses are also reduced by using f...

  4. Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography-positive electrospray ionisation tandem mass spectrometry.

    Science.gov (United States)

    Baker, David R; Kasprzyk-Hordern, Barbara

    2011-03-25

    A new-multi residue method was developed for the environmental monitoring of 65 stimulants, opiod and morphine derivatives, benzodiazepines, antidepressants, dissociative anaesthetics, drug precursors, human urine indicators and their metabolites in wastewater and surface water. The proposed analytical methodology offers rapid analysis for a large number of compounds, with low limits of quantification and utilises only one solid-phase extraction-ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry (SPE-LC-MS/MS) method, thus overcoming the drawbacks of previously published procedures. The method employed solid phase extraction with the usage of Oasis MCX sorbent and subsequent ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry. The usage of a 1.7 μm particle size column (1 mm×150 mm) resulted in very low flow rates (0.04 mLmin(-1)), and as a consequence gave good sensitivity, low mobile phase consumption and short retention times for all compounds (from 2.9 to 23.1 min). High SPE recoveries (>60%) were obtained for the majority of compounds. The mean correlation coefficients of the calibration curves were typically higher than 0.997 and showed good linearity in the range 0-1000 μgL(-1). The method limits of detection ranged from 0.1 ngL(-1) for compounds including cocaine, benzoylecgonine, norbenzoylecgonine and 2-oxo-3-hydroxy-LSD to 100 ngL(-1) for caffeine. Method quantification limits ranged from 0.5 to 154.2 ngL(-1). Intra- and inter-day repeatabilities were on average less than 10%. The method accuracy range was within -33.1 to 30.1%. The new multi-residue method was used to analyse drugs of abuse in wastewater and river water in the UK environment. Of the targeted 65 compounds, 46 analytes were detected at levels above the method quantification limit (MQL) in wastewater treatment plant (WWTP) influent, 43 in WWTP effluent and 36 compounds in river water. Copyright

  5. Global alteration of the drug-binding pocket of human P-glycoprotein (ABCB1) by substitution of fifteen conserved residues reveals a negative correlation between substrate size and transport efficiency.

    Science.gov (United States)

    Vahedi, Shahrooz; Chufan, Eduardo E; Ambudkar, Suresh V

    2017-11-01

    P-glycoprotein (P-gp), an ATP-dependent efflux pump, is linked to the development of multidrug resistance in cancer cells. However, the drug-binding sites and translocation pathways of this transporter are not yet well-characterized. We recently demonstrated the important role of tyrosine residues in regulating P-gp ATP hydrolysis via hydrogen bond formations with high affinity modulators. Since tyrosine is both a hydrogen bond donor and acceptor, and non-covalent interactions are key in drug transport, in this study we investigated the global effect of enrichment of tyrosine residues in the drug-binding pocket on the drug binding and transport function of P-gp. By employing computational analysis, 15 conserved residues in the drug-binding pocket of human P-gp that interact with substrates were identified and then substituted with tyrosine, including 11 phenylalanine (F72, F303, F314, F336, F732, F759, F770, F938, F942, F983, F994), two leucine (L339, L975), one isoleucine (I306), and one methionine (M949). Characterization of the tyrosine-rich P-gp mutant in HeLa cells demonstrated that this major alteration in the drug-binding pocket by introducing fifteen additional tyrosine residues is well tolerated and has no measurable effect on total or cell surface expression of this mutant. Although the tyrosine-enriched mutant P-gp could transport small to moderate size (transport large (>1000 Daltons) substrates such as NBD-cyclosporine A, Bodipy-paclitaxel and Bodipy-vinblastine was significantly decreased. This was further supported by the physico-chemical characterization of seventeen tested substrates, which revealed a negative correlation between drug transport and molecular size for the tyrosine-enriched P-gp mutant. Published by Elsevier Inc.

  6. 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.

  7. Multi-residue analysis of veterinary drugs, pesticides and mycotoxins in dairy products by liquid chromatography-tandem mass spectrometry using low-temperature cleanup and solid phase extraction.

    Science.gov (United States)

    Xie, Jie; Peng, Tao; Zhu, Ailing; He, Jianli; Chang, Qiaoying; Hu, Xueyan; Chen, Hui; Fan, Chunlin; Jiang, Wenxiao; Chen, Min; Li, Jiancheng; Ding, Shuangyang; Jiang, Haiyang

    2015-10-01

    A multi-class multi-residue analysis method for determination of veterinary drugs, pesticides and mycotoxins in dairy products by liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been established. These 17 classes, a total of 40 kinds of target compounds were chosen because their administration to food-producing animals is banned or regulated in China and may be potentially abused or misused. Samples were extracted with acetonitrile-ethyl acetate-acetic acid (49.5+49.5+1, v/v/v). Most of lipids in the extract were removed by low-temperature cleanup, prior to solid phase extraction on HLB cartridges. The quantification and confirmation of the 40 analytes were performed by LC-MS/MS with electro-spray ionization (ESI) interface in multiple reaction monitoring (MRM) mode. The limits of detection (LODs) and limits of quantification (LOQs) were 0.006-0.3μg/kg and 0.02-1.0μg/kg, respectively. The spiked recoveries in milk, yogurt, milk powder and cheese samples were from 67.3% to 106.9%. The repeatability and the within-laboratory reproducibility were less than 12.7% and 13.9%. Applying this method, our results revealed the presences of chloramphenicol, cimeterol, and flunixin at the concentration of 0.027-0.452μg/kg in some samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Concentration profiling in rat tissue by high-resolution magic-angle spinning NMR spectroscopy: investigation of a model drug.

    Science.gov (United States)

    Lucas, Laura H; Wilson, Sarah F; Lunte, Craig E; Larive, Cynthia K

    2005-05-01

    The utility of high-resolution magic-angle spinning (HR-MAS) NMR for studying drug delivery in whole tissues was explored by dosing female Sprague-Dawley rats with topical or injectable benzoic acid (BA). In principle, HR-MAS NMR permits the detection of both intra- and extracellular compounds. This is an advantage over the previous detection of topically applied BA using microdialysis coupled to HPLC/UV as microdialysis samples only the extracellular space. Skin and muscle samples were analyzed by (1)H HR-MAS NMR, and BA levels were determined using an external standard solution added to the sample rotor. One to two percent of the BA topical dose was detected in the muscle, showing that BA penetrated through the dermal and subcutaneous layers. Since BA was not detected in the muscle in the microdialysis studies, the NMR spectra revealed the intracellular localization of BA. The amount of BA detected in muscle after subcutaneous injection correlated with the distance from the dosing site. Overall, the results suggest that HR-MAS NMR can distinguish differences in the local concentration of BA varying with tissue type, dosage method, and tissue proximity to the dosing site. The results illustrate the potential of this technique for quantitative analysis of drug delivery and distribution and the challenges to be addressed as the method is refined.

  9. Acetylation and glycation of fibrinogen in vitro occur at specific lysine residues in a concentration dependent manner: A mass spectrometric and isotope labeling study

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Jan, E-mail: jan.svensson@ki.se [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden); Bergman, Ann-Charlotte [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Adamson, Ulf [Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden); Blombaeck, Margareta [Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital (Solna), SE-171 76 Stockholm (Sweden); Wallen, Hakan; Joerneskog, Gun [Karolinska Institutet, Department of Clinical Sciences, Danderyd Hospital, SE-182 88 Stockholm (Sweden)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Fibrinogen was incubated in vitro with glucose or aspirin. Black-Right-Pointing-Pointer Acetylations and glycations were found at twelve lysine sites by mass spectrometry. Black-Right-Pointing-Pointer The labeling by aspirin and glucose occurred dose-dependently. Black-Right-Pointing-Pointer No competition between glucose and aspirin for binding to fibrinogen was found. -- Abstract: Aspirin may exert part of its antithrombotic effects through platelet-independent mechanisms. Diabetes is a condition in which the beneficial effects of aspirin are less prominent or absent - a phenomenon called 'aspirin resistance'. We investigated whether acetylation and glycation occur at specific sites in fibrinogen and if competition between glucose and aspirin in binding to fibrinogen occurs. Our hypothesis was that such competition might be one explanation to 'aspirin resistance' in diabetes. After incubation of fibrinogen in vitro with aspirin (0.8 mM, 24 h) or glucose (100 mM, 5-10 days), we found 12 modified sites with mass spectrometric techniques. Acetylations in the {alpha}-chain: {alpha}K191, {alpha}K208, {alpha}K224, {alpha}K429, {alpha}K457, {alpha}K539, {alpha}K562, in the {beta}-chain: {beta}K233, and in the {gamma}-chain: {gamma}K170 and {gamma}K273. Glycations were found at {beta}K133 and {gamma}K75, alternatively {gamma}K85. Notably, the lysine 539 is a site involved in FXIII-mediated cross-linking of fibrin. With isotope labeling in vitro, using [{sup 14}C-acetyl]salicylic acid and [{sup 14}C]glucose, a labeling of 0.013-0.084 and 0.12-0.5 mol of acetylated and glycated adduct/mol fibrinogen, respectively, was found for clinically (12.9-100 {mu}M aspirin) and physiologically (2-8 mM glucose) relevant plasma concentrations. No competition between acetylation and glycation could be demonstrated. Thus, fibrinogen is acetylated at several lysine residues, some of which are involved in the cross-linking of

  10. Acetylation and glycation of fibrinogen in vitro occur at specific lysine residues in a concentration dependent manner: A mass spectrometric and isotope labeling study

    International Nuclear Information System (INIS)

    Svensson, Jan; Bergman, Ann-Charlotte; Adamson, Ulf; Blombäck, Margareta; Wallén, Håkan; Jörneskog, Gun

    2012-01-01

    Highlights: ► Fibrinogen was incubated in vitro with glucose or aspirin. ► Acetylations and glycations were found at twelve lysine sites by mass spectrometry. ► The labeling by aspirin and glucose occurred dose-dependently. ► No competition between glucose and aspirin for binding to fibrinogen was found. -- Abstract: Aspirin may exert part of its antithrombotic effects through platelet-independent mechanisms. Diabetes is a condition in which the beneficial effects of aspirin are less prominent or absent – a phenomenon called “aspirin resistance”. We investigated whether acetylation and glycation occur at specific sites in fibrinogen and if competition between glucose and aspirin in binding to fibrinogen occurs. Our hypothesis was that such competition might be one explanation to “aspirin resistance” in diabetes. After incubation of fibrinogen in vitro with aspirin (0.8 mM, 24 h) or glucose (100 mM, 5–10 days), we found 12 modified sites with mass spectrometric techniques. Acetylations in the α-chain: αK191, αK208, αK224, αK429, αK457, αK539, αK562, in the β-chain: βK233, and in the γ-chain: γK170 and γK273. Glycations were found at βK133 and γK75, alternatively γK85. Notably, the lysine 539 is a site involved in FXIII-mediated cross-linking of fibrin. With isotope labeling in vitro, using [ 14 C-acetyl]salicylic acid and [ 14 C]glucose, a labeling of 0.013–0.084 and 0.12–0.5 mol of acetylated and glycated adduct/mol fibrinogen, respectively, was found for clinically (12.9–100 μM aspirin) and physiologically (2–8 mM glucose) relevant plasma concentrations. No competition between acetylation and glycation could be demonstrated. Thus, fibrinogen is acetylated at several lysine residues, some of which are involved in the cross-linking of fibrinogen. This may mechanistically explain why aspirin facilitates fibrin degradation. We find no support for the idea that glycation of fibrin(ogen) interferes with acetylation of

  11. Antibiotic Residues - A Global Health Hazard

    Directory of Open Access Journals (Sweden)

    Nisha A.R.

    Full Text Available Use of Antibiotic that might result in deposition of residues in meat, milk and eggs must not be permitted in food intended for human consumption. If use of antibiotics is necessary as in prevention and treatment of animal diseases, a withholding period must be observed until the residues are negligible or no longer detected. The use of antibiotics to bring about improved performance in growth and feed efficiency, to synchronize or control of reproductive cycle and breeding performance also often lead to harmful residual effects. Concern over antibiotic residues in food of animal origin occurs in two times; one which produces potential threat to direct toxicity in human, second is whether the low levels of antibiotic exposure would result in alteration of microflora, cause disease and the possible development of resistant strains which cause failure of antibiotic therapy in clinical situations. A withdrawal period is established to safeguard human from exposure of antibiotic added food. The withdrawal time is the time required for the residue of toxicological concern to reach safe concentration as defined by tolerance. It is the interval from the time an animal is removed from medication until permitted time of slaughter. Heavy responsibility is placed on the veterinarian and livestock producer to observe the period for a withdrawal of a drug prior to slaughter to assure that illegal concentration of drug residue in meat, milk and egg do not occur. Use of food additives may improve feed efficiency 17% in beef cattle, 10% in lambs, 15% in poultry and 15% in swine. But their indiscriminate use will produce toxicity in consumers. WHO and FAO establish tolerances for a drug, pesticide or other chemical in the relevant tissues of food producing animals. The tolerance is the tissue concentration below, which a marker residue for the drug or chemical must fall in the target tissue before that animal edible tissues are considered safe for human

  12. Improving yield and composition of protein concentrates from green tea residue in an agri-food supply chain: Effect of pre-treatment

    NARCIS (Netherlands)

    Zhang, Chen; Krimpen, Van Marinus M.; Sanders, Johan P.M.; Bruins, Marieke E.

    2016-01-01

    Rather than improving crop-production yield, developing biorefinery technology for unused biomass from the agri-food supply chain may be the crucial factor to reach sustainable global food security. A successful example of food-driven biorefinery is the extraction of protein from green tea residues,

  13. 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

  14. Mixed solvency concept in reducing surfactant concentration of self-emulsifying drug delivery systems of candesartan cilexetil using D-optimal mixture design

    OpenAIRE

    Chandna Chandan; R K Maheshwari

    2013-01-01

    The objective of this present study was to explore the utility of "mixed solvency" concept to enhance the solubility of poorly-water soluble drug, candesartan cilexetil (CC) in modified solubilizer system. The objective of this paper is to reduce the surfactant concentration traditionally involved in the formulation of self-emulsifying drug delivery systems (SEDDS) by proposing an alternate system of solubilizer to provide novel surfactant/cosurfactant system, to aid traditionally involved co...

  15. Uncovering the local inelastic interactions during manufacture of ductile cast iron: How the substructure of the graphite particles can induce residual stress concentrations in the matrix

    DEFF Research Database (Denmark)

    Andriollo, Tito; Hellström, Kristina; Sonne, Mads Rostgaard

    2018-01-01

    Recent X-ray diffraction (XRD) measurements have revealed that plastic deformation and a residual elastic strain field can be present around the graphite particles in ductile cast iron after manufacturing, probably due to some local mismatch in thermal contraction. However, as only one component...... of the elastic strain tensor could be obtained from the XRD data, the shape and magnitude of the associated residual stress field have remained unknown. To compensate for this and to provide theoretical insight into this unexplored topic, a combined experimental-numerical approach is presented in this paper....... First, a ma terial equivalent to the ductile cast iron matrix is manufactured and subjected to dilato- metric and high-temperature tensile tests. Subsequently, a two-scale hierarchical top-down model is devised, calibrated on the basis of the collected data and used to simulate the interaction between...

  16. Food toxicology. Residues and contaminants: Risks and consumer protection; Lebensmitteltoxikologie. Rueckstaende und Kontaminanten: Risiken und Verbraucherschutz

    Energy Technology Data Exchange (ETDEWEB)

    Nau, H. [Tieraerztliche Hochschule Hannover, ZA Lebensmitteltoxikologie (Germany); Steinberg, P. [Potsdam Univ., Inst. fuer Ernaehrungswissenschaft (Germany); Kietzmann, M. (eds.) [Tieraerztliche Hochschule Hannover, Inst. fuer Pharmakologie, Toxikologie/Pharmazie (Germany)

    2003-07-01

    In a detailed introduction, the basic methods of risk assessment for potentially toxic food constituents are presented as well as the analytical methods applied for measuring even very small concentrations of contaminants. The main classes of substances relevant in foods ar represented, i.e. animal drugs, fungicides and herbicides, natural toxins, contaminants, prions from BSE-infested animals and residues of 'new' proteins and 'new' DNA from genetically modified foods. New legislation in Germany and Europe is presented including the National Residue Monitoring Plant which is to enable annual monitoring of residue concentrations in foods derived from animals. (orig.)

  17. Control of residual carbon concentration in GaN high electron mobility transistor and realization of high-resistance GaN grown by metal-organic chemical vapor deposition

    Energy Technology Data Exchange (ETDEWEB)

    He, X.G. [State Key Laboratory on Integrated Optoelectronics, Institute of Semiconductors, Chinese Academy of Sciences, P.O. Box 912, Beijing 100083 (China); Zhao, D.G., E-mail: dgzhao@red.semi.ac.cn [State Key Laboratory on Integrated Optoelectronics, Institute of Semiconductors, Chinese Academy of Sciences, P.O. Box 912, Beijing 100083 (China); Jiang, D.S.; Liu, Z.S.; Chen, P.; Le, L.C.; Yang, J.; Li, X.J. [State Key Laboratory on Integrated Optoelectronics, Institute of Semiconductors, Chinese Academy of Sciences, P.O. Box 912, Beijing 100083 (China); Zhang, S.M.; Zhu, J.J.; Wang, H.; Yang, H. [Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of Sciences, Suzhou 215125 (China)

    2014-08-01

    GaN films were grown by metal-organic chemical vapor deposition (MOCVD) under various growth conditions. The influences of MOCVD growth parameters, i.e., growth pressure, ammonia (NH{sub 3}) flux, growth temperature, trimethyl-gallium flux and H{sub 2} flux, on residual carbon concentration ([C]) were systematically investigated. Secondary ion mass spectroscopy measurements show that [C] can be effectively modulated by growth conditions. Especially, it can increase by reducing growth pressure up to two orders of magnitude. High-resistance (HR) GaN epilayer with a resistivity over 1.0 × 10{sup 9} Ω·cm is achieved by reducing growth pressure. The mechanism of the formation of HR GaN epilayer is discussed. An Al{sub x}Ga{sub 1−x}N/GaN high electron mobility transistor structure with a HR GaN buffer layer and an additional low-carbon GaN channel layer is presented, exhibiting a high two dimensional electron gas mobility of 1815 cm{sup 2}/Vs. - Highlights: • Influence of MOCVD parameters on residual carbon concentration in GaN is studied. • GaN layer with a resistivity over 1 × 10{sup 9} Ω·cm is achieved by reducing growth pressure. • High electron mobility transistor (HEMT) structures were prepared. • Control of residual carbon content results in HEMT with high 2-D electron gas mobility.

  18. Residuation theory

    CERN Document Server

    Blyth, T S; Sneddon, I N; Stark, M

    1972-01-01

    Residuation Theory aims to contribute to literature in the field of ordered algebraic structures, especially on the subject of residual mappings. The book is divided into three chapters. Chapter 1 focuses on ordered sets; directed sets; semilattices; lattices; and complete lattices. Chapter 2 tackles Baer rings; Baer semigroups; Foulis semigroups; residual mappings; the notion of involution; and Boolean algebras. Chapter 3 covers residuated groupoids and semigroups; group homomorphic and isotone homomorphic Boolean images of ordered semigroups; Dubreil-Jacotin and Brouwer semigroups; and loli

  19. 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.

  20. [Analysis of residues of organochlorine compounds in plant drugs. 3. Identification of residues of polychlorobiphenyl compounds by comparison of gas chromatography on packed and capillary columns and GCMS coupling].

    Science.gov (United States)

    Benecke, R; Brotka, J; Wijsbeek, J; Franke, J P; Bruins, A P; de Zeeuw, R A

    1988-02-01

    The identification of residues of polychlorinated biphenyls in a test sample of Flores Chamomillae could be achieved by the retention behavior at gas chromatographic analyses on packed and capillary columns compared with reference standard Clophen A 60, respectively as well as well by capillary GC/MS using single ion monitoring of substance-characteristic ion mass.

  1. Feeding toxicity and impact of imidacloprid formulation and mixtures with six representative pesticides at residue concentrations on honey bee physiology (Apis mellifera)

    OpenAIRE

    Zhu, Yu Cheng; Yao, Jianxiu; Adamczyk, John; Luttrell, Randall

    2017-01-01

    Imidacloprid is the most widely used insecticide in agriculture. In this study, we used feeding methods to simulate in-hive exposures of formulated imidacloprid (Advise® 2FL) alone and mixtures with six representative pesticides for different classes. Advise, fed at 4.3 mg/L (equal to maximal residue detection of 912 ppb active ingredient [a.i.] in pollen) induced 36% mortality and 56% feeding suppression after 2-week feeding. Treatments with individual Bracket (acephate), Karate (λ-cyhalothr...

  2. Weld Residual Stress in Corner Boxing Joints

    OpenAIRE

    Kazuyoshi, Matsuoka; Tokuharu, Yoshii; Ship Research Institute, Ministry of Transport; Ship Research Institute, Ministry of Transport

    1998-01-01

    Fatigue damage often occurs in corner boxing welded joints because of stress concentration and residual stress. The hot spot stress approach is applicable to stress concentration. However, the number of suitable methods for estimating residual stress in welded joints is limited. The purpose of this paper is to clarify the residual stress in corner boxing joints. The method of estimating residual stresses based on the inherent stress technique is presented. Residual stress measurements are per...

  3. Determination of the Minimum Inhibitory Concentration of the Barberry Extract and the Dried Residue of Red Grape and Their Effects on the Growth Inhibition of Sausage Bacteria by Using Response Surface Methodology (RSM

    Directory of Open Access Journals (Sweden)

    Fatemeh Riazi

    2015-09-01

    Full Text Available Background and Objectives: With regard to the hazards of nitrite, application of natural preservatives in order to reduce the microbial load of meat and meat products is increasing. Owing to their anti-bacterial properties, red barberry and the dried residue of red grape could be suitable replacers for nitrite. Materials and Methods: Agar dilution method was employed in order to determine the minimum inhibitory concentration (MIC of the barberry extract and the dried residue of red grape. The anti-microbial effects of the barberry extract (0-600 mg/kg, the dried residue of red grape (0-2% and nitrite (30-90 mg/kg were investigated on the total viable counts of Clostridium perfringens, as well as on the psychrophilic bacteria after 30 days of storage at 4°C. Finally, the effects of the three independent variables in the optimal sample were examined on the growth of the inoculated C. perfringens. Results: The MIC of the barberry extract and the dried residue of red grape on Staphylococcus aureus was 3 and 6 (mg/ml, respectively. In the case of Escherichia coli, it was 4 and 7 (mg/ml, respectively. The barberry extract and nitrite reduced the growth of the living aerobic bacteria significantly. The spores of the inoculated C. perfringens had no growth in the optimum sample during storage. Conclusions: The barberry extract and the dried residue of red grape as natural preservatives, could partially substitute for nitrite in order to reduce the microbial load of sausage.

  4. 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.

  5. Increase in the carbohydrate content of the microalgae Spirulina in culture by nutrient starvation and the addition of residues of whey protein concentrate.

    Science.gov (United States)

    Vieira Salla, Ana Cláudia; Margarites, Ana Cláudia; Seibel, Fábio Ivan; Holz, Luiz Carlos; Brião, Vandré Barbosa; Bertolin, Telma Elita; Colla, Luciane Maria; Costa, Jorge Alberto Vieira

    2016-06-01

    Non-renewable sources that will end with time are the largest part of world energy consumption, which emphasizes the necessity to develop renewable sources of energy. This necessity has created opportunities for the use of microalgae as a biofuel. The use of microalgae as a feedstock source for bioethanol production requires high yields of both biomass and carbohydrates. With mixotrophic cultures, wastewater can be used to culture algae. The aim of the study was to increase the carbohydrate content in the microalgae Spirulina with the additions of residues from the ultra and nanofiltration of whey protein. The nutrient deficit in the Zarrouk medium diluted to 20% and the addition of 2.5% of both residue types led to high carbohydrate productivity (60 mg L(-1) d(-1)). With these culture conditions, the increase in carbohydrate production in Spirulina indicated that the conditions were appropriate for use with microalgae as a feedstock in the production of bioethanol. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Eimeria oocyst concentrations and species composition in litter from commercial broiler farms during anticoccidial drug or live Eimeria oocyst vaccine control programs

    Science.gov (United States)

    The purpose of this study was to determine if Eimeria oocyst concentrations and species composition in commercial broiler house litter changed during different cycles of anticoccidial drug (ACD) or live Eimeria oocyst vaccine (VAC) control programs, and if there was a correlation between Eimeria ooc...

  7. Tissue Drug Concentrations of Anti-tumor Necrosis Factor Agents Are Associated with the Long-term Outcome of Patients with Crohn's Disease.

    Science.gov (United States)

    Yoshihara, Takeo; Shinzaki, Shinichiro; Kawai, Shoichiro; Fujii, Hironobu; Iwatani, Shuko; Yamaguchi, Toshio; Araki, Manabu; Hiyama, Satoshi; Inoue, Takahiro; Hayashi, Yoshito; Watabe, Kenji; Iijima, Hideki; Takehara, Tetsuo

    2017-12-01

    Many reports indicate that a high-serum trough level of anti-tumor necrosis factor (TNF) agents is required for sustained remission in patients with Crohn's disease The pharmacokinetics of anti-TNF agents in inflamed intestinal tissue, however, is not well investigated. We investigated the association between the tissue concentration of anti-TNF agents and long-term disease outcome. This was a prospective single-center study that enrolled 25 patients with Crohn's disease who were administered infliximab or adalimumab. All participants underwent endoscopy 2 weeks after administration of the anti-TNF agents, and biopsy samples were obtained from both inflamed and noninflamed intestinal tissue. Tissue concentrations of anti-TNF agents were evaluated and the correlation with serum trough levels was compared. The relation between the tissue drug concentration and clinical course over 24 months was also investigated. Concentrations of anti-TNF agents were significantly higher in inflamed tissue than in noninflamed tissue. Patients with high-serum trough concentrations of anti-TNF agents had significantly higher drug levels in the noninflamed tissue than those with low-serum trough concentrations, but no difference in the levels was detected in the inflamed tissue. Patients with high-drug levels in the noninflamed tissue had a significantly higher sustained response rate than patients with low-drug levels. Concentrations of anti-TNF agents in the noninflamed tissue can reflect sustained remission and may be a useful biomarker for monitoring therapeutic intensity in patients with Crohn's disease treated with anti-TNF agents (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B623).

  8. Monte Carlo Simulations Suggest Current Chlortetracycline Drug-Residue Based Withdrawal Periods Would Not Control Antimicrobial Resistance Dissemination from Feedlot to Slaughterhouse

    Directory of Open Access Journals (Sweden)

    Casey L. Cazer

    2017-09-01

    Full Text Available Antimicrobial use in beef cattle can increase antimicrobial resistance prevalence in their enteric bacteria, including potential pathogens such as Escherichia coli. These bacteria can contaminate animal products at slaughterhouses and cause food-borne illness, which can be difficult to treat if it is due to antimicrobial resistant bacteria. One potential intervention to reduce the dissemination of resistant bacteria from feedlot to consumer is to impose a withdrawal period after antimicrobial use, similar to the current withdrawal period designed to prevent drug residues in edible animal meat. We investigated tetracycline resistance in generic E. coli in the bovine large intestine during and after antimicrobial treatment by building a mathematical model of oral chlortetracycline pharmacokinetics-pharmacodynamics and E. coli population dynamics. We tracked three E. coli subpopulations (susceptible, intermediate, and resistant during and after treatment with each of three United States chlortetracycline indications (liver abscess reduction, disease control, disease treatment. We compared the proportion of resistant E. coli before antimicrobial use to that at several time points after treatment and found a greater proportion of resistant enteric E. coli after the current withdrawal periods than prior to treatment. In order for the proportion of resistant E. coli in the median beef steer to return to the pre-treatment level, withdrawal periods of 15 days after liver abscess reduction dosing (70 mg daily, 31 days after disease control dosing (350 mg daily, and 36 days after disease treatment dosing (22 mg/kg bodyweight for 5 days are required in this model. These antimicrobial resistance withdrawal periods would be substantially longer than the current U.S. withdrawals of 0–2 days or Canadian withdrawals of 5–10 days. One published field study found similar time periods necessary to reduce the proportion of resistant E. coli following

  9. A Critical Review of the Current Evidence for Measuring Drug Concentrations of First-Line Agents Used to Treat Tuberculosis in Children.

    Science.gov (United States)

    Wilby, Kyle John; Shabana, Sara; Ensom, Mary H H; Marra, Fawziah

    2016-01-01

    Tuberculosis is a leading cause of infectious disease-related morbidity and mortality worldwide. Additionally, treatment is complex with most patients requiring combination therapy of first-line agents for multiple months. Children are especially at risk from the medications used to treat tuberculosis and therefore interventions to optimize both efficacy and safety are needed. Protocols exist for therapeutic drug monitoring in tuberculosis patients yet there is a gap in knowledge regarding the extent of any benefits achieved, especially in children. This review aims to summarize and evaluate literature reporting outcomes related to the measurement of drug concentrations of first-line agents used to treat tuberculosis (rifampin, isoniazid, pyrazinamide, ethambutol) in children. Findings showed a lack of strong evidence to support therapeutic drug monitoring in children with tuberculosis. Standard weight-based dosing of first-line agents does not commonly achieve target concentrations yet the effect on clinical outcomes remains unclear. As such, therapeutic drug monitoring should not be recommended currently as a widespread practice for all children with tuberculosis. However, future research should assess any benefit in special populations such as those with relapsing or recurrent disease, or those presenting with adverse drug reactions.

  10. 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......-enantiomers (Wilcoxon's test, p methadone only, methadone and strong analgesics, methadone and benzodiazepines, or methadone and other drugs). There was no significant difference in any of the R-methadone/total methadone ratios among......- and S-methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine. No significant association was detected....

  11. Health implications of water quality: drugs residues in water Repercusiones sanitarias de la calidad del agua: los residuos de medicamentos en el agua

    Directory of Open Access Journals (Sweden)

    Damià Barceló Culleres

    2011-12-01

    Full Text Available This manuscript summarizes the main results obtained in various monitoring studies conducted in the Llobregat and the Ebro River basins to evaluate the occurrence of pharmaceuticals and drugs of abuse in their aquatic environments and the potentially derived risks for environmental and human health. The occurrence of these compounds in surface waters, located downstream the point of discharge of sewage treatment plants (STP, points out STPs effluents as the main source of these substances in the aquatic environment. Both river basins had similar pharmaceutical contamination patterns. However, hazard quotients (HQ calculated for three different trophic levels (algae, daphnia and fish pointed out sulfamethoxazol (sulfamide antibiotic for algae, gemfibrozil (lipid regulator for algae and fish, clofibric acid (lipid regulator and erythromycine (macrolide antibiotic for daphnia, and ibuprofen (analgesic anti-inflammatory for all investigated tropic levels, as the compounds with the highest ecotoxicological risk in the Llobregat. In the Ebro River, the most problematic pharmaceuticals were sulfamethoxazol for algae, and erythromycine, clofibric acid and fluoxetine (anti-depressive for daphnids. Levels of drugs of abuse measured in surface waters of the Ebro River were one and two orders of magnitude lower than those observed in effluent and influent sewage waters, respectively. Lack of data about their ecotoxicity does not allow calculation of HQ for these compounds. The presence of pharmaceuticals and drugs of abuse in surface and drinking waters is not subjected to regulation; hence, they are not considered priority pollutants to be included in monitoring programs. However, due to their possible harmful outcomes in wildlife, research on their potential effects in human health is indispensable.Este trabajo resume varios estudios de monitorización de fármacos y drogas de abuso llevados a cabo en el medio ambiente acuático de las cuencas de los r

  12. Hole traps associated with high-concentration residual carriers in p-type GaAsN grown by chemical beam epitaxy

    Energy Technology Data Exchange (ETDEWEB)

    Elleuch, Omar, E-mail: mr.omar.elleuch@gmail.com; Wang, Li; Lee, Kan-Hua; Demizu, Koshiro; Ikeda, Kazuma; Kojima, Nobuaki; Ohshita, Yoshio; Yamaguchi, Masafumi [Toyota Technological Institute, 2-12-1 Hisakata, Tempaku, Nagoya 468-8511 (Japan)

    2015-01-28

    The hole traps associated with high background doping in p-type GaAsN grown by chemical beam epitaxy are studied based on the changes of carrier concentration, junction capacitance, and hole traps properties due to the annealing. The carrier concentration was increased dramatically with annealing time, based on capacitance–voltage (C–V) measurement. In addition, the temperature dependence of the junction capacitance (C–T) was increased rapidly two times. Such behavior is explained by the thermal ionization of two acceptor states. These acceptors are the main cause of high background doping in the film, since the estimated carrier concentration from C–T results explains the measured carrier concentration at room temperature using C–V method. The acceptor states became shallower after annealing, and hence their structures are thermally unstable. Deep level transient spectroscopy (DLTS) showed that the HC2 hole trap was composed of two signals, labeled HC21 and HC22. These defects correspond to the acceptor levels, as their energy levels obtained from DLTS are similar to those deduced from C–T. The capture cross sections of HC21 and HC22 are larger than those of single acceptors. In addition, their energy levels and capture cross sections change in the same way due to the annealing. This tendency suggests that HC21 and HC22 signals originate from the same defect which acts as a double acceptor.

  13. Hole traps associated with high-concentration residual carriers in p-type GaAsN grown by chemical beam epitaxy

    International Nuclear Information System (INIS)

    Elleuch, Omar; Wang, Li; Lee, Kan-Hua; Demizu, Koshiro; Ikeda, Kazuma; Kojima, Nobuaki; Ohshita, Yoshio; Yamaguchi, Masafumi

    2015-01-01

    The hole traps associated with high background doping in p-type GaAsN grown by chemical beam epitaxy are studied based on the changes of carrier concentration, junction capacitance, and hole traps properties due to the annealing. The carrier concentration was increased dramatically with annealing time, based on capacitance–voltage (C–V) measurement. In addition, the temperature dependence of the junction capacitance (C–T) was increased rapidly two times. Such behavior is explained by the thermal ionization of two acceptor states. These acceptors are the main cause of high background doping in the film, since the estimated carrier concentration from C–T results explains the measured carrier concentration at room temperature using C–V method. The acceptor states became shallower after annealing, and hence their structures are thermally unstable. Deep level transient spectroscopy (DLTS) showed that the HC2 hole trap was composed of two signals, labeled HC21 and HC22. These defects correspond to the acceptor levels, as their energy levels obtained from DLTS are similar to those deduced from C–T. The capture cross sections of HC21 and HC22 are larger than those of single acceptors. In addition, their energy levels and capture cross sections change in the same way due to the annealing. This tendency suggests that HC21 and HC22 signals originate from the same defect which acts as a double acceptor

  14. [Plant drugs with residues of organochlorine compounds. 2. Identification of residues of DDT and its analogs by comparison of gas chromatography on packed and capillary columns and GC/MS coupling].

    Science.gov (United States)

    Benecke, R; Brotka, J; Wijsbeek, J; Franke, J P; Bruins, A P; de Zeeuw, R A

    1986-07-01

    For the GC analysis of DDT isomers and metabolites in extracts of Flores Chamomillae end Radix Valerianae the separation on a packed QF-1/OV-17 column was compared with various capillary columns of the CP-Sil type. Identification of the individual compounds could be achieved by comparing the retention behavior, chemical transformation of DDT and DDE, as well as by capillary GC-MS using single ion monitoring of substance-characteristic ion mass. In this way, residues of p,p'-DDT, o,p'-DDE and p,p'-TDE could be identified.

  15. Residue processing

    Energy Technology Data Exchange (ETDEWEB)

    Gieg, W.; Rank, V.

    1942-10-15

    In the first stage of coal hydrogenation, the liquid phase, light and heavy oils were produced; the latter containing the nonliquefied parts of the coal, the coal ash, and the catalyst substances. It was the problem of residue processing to extract from these so-called let-down oils that which could be used as pasting oils for the coal. The object was to obtain a maximum oil extraction and a complete removal of the solids, because of the latter were returned to the process they would needlessly burden the reaction space. Separation of solids in residue processing could be accomplished by filtration, centrifugation, extraction, distillation, or low-temperature carbonization (L.T.C.). Filtration or centrifugation was most suitable since a maximum oil yield could be expected from it, since only a small portion of the let-down oil contained in the filtration or centrifugation residue had to be thermally treated. The most satisfactory centrifuge at this time was the Laval, which delivered liquid centrifuge residue and centrifuge oil continuously. By comparison, the semi-continuous centrifuges delivered plastic residues which were difficult to handle. Various apparatus such as the spiral screw kiln and the ball kiln were used for low-temperature carbonization of centrifuge residues. Both were based on the idea of carbonization in thin layers. Efforts were also being made to produce electrode carbon and briquette binder as by-products of the liquid coal phase.

  16. Radionuclide concentration variations in the fuel and residues of oil shale-fired power plants: Estimations of the radiological characteristics over a 2-year period.

    Science.gov (United States)

    Vaasma, Taavi; Loosaar, Jüri; Kiisk, Madis; Tkaczyk, Alan Henry

    2017-07-01

    Several multi-day samplings were conducted over a 2-year period from an oil shale-fired power plant operating with pulverized fuel type of boilers that were equipped with either novel integrated desulphurization system and bag filters or with electrostatic precipitators. Oil shale, bottom ash and fly ash samples were collected and radionuclides from the 238 U and 232 Th series as well as 40 K were determined. The work aimed at determining possible variations in the concentrations of naturally occurring radionuclides within the collected samples and detect the sources of these fluctuations. During the continuous multi-day samplings, various boiler parameters were recorded as well. With couple of exceptions, no statistically significant differences were detected (significance level 0.05) between the measured radionuclide mean values in various ash samples within the same sampling. When comparing the results between multiple years and samplings, no statistically significant variations were observed between 238 U and 226 Ra values. However, there were significant differences between the values in the fly ashes when comparing 210 Pb, 40 K, 228 Ra and 232 Th values between the various samplings. In all cases the radionuclide activity concentrations in the specific fly ash remained under 100 Bq kg -1 , posing no radiological concerns when using this material as an additive in construction or building materials. Correlation analysis between the registered boiler parameters and measured radionuclide activity concentrations showed weak or no correlation. The obtained results suggest that the main sources of variations are due to the characteristics of the used fuel. The changes in the radionuclide activity concentrations between multiple years were in general rather modest. The radionuclide activity concentrations varied dominantly between 4% and 15% from the measured mean within the same sampling. The relative standard deviation was however within the same range as the

  17. Integrated project: Microbiological and physiological studies on the presence of residual concentrations in mineral-oil-contaminated soils after rehabilitation. Final report. Pt. 2; Mikrobiologische und physiologische Untersuchungen zur Frage der Restkonzentration bei der Sanierung mineraloelkontaminierter Boeden. Abschlussbericht. T. 2

    Energy Technology Data Exchange (ETDEWEB)

    Miethe, D.; Riis, V.; Stimming, M.

    1996-01-04

    It has been known for a long time that microorganisms are able to utilise mineral oils. Today various methods are practised which exploit autochthonous microorganisms` ability to utilise mineral oils. The main problem of microbial decomposition of hydrocarbons is that mineral oil residues remain. The aim of the present research project was therefore to determine the limits of the metabolisability of the substrate and find out why residues remain. Mineral oils and residual fractions differ markedly in their decomposability. Intermediate distillates are easily decomposed to a degree of 95-97% by well-adapted consorts. For high-boiling mineral oils (bp>400 C) the degree of decomposition is approx. 60%. Extracts from contaminated sites range from 40 to 60% in their degree of decomposability. The incomplete microbial decomposition of mineral oils is mainly due to their structure. There remain chemically and thermally extremely, inert hydrocarbons (mainly aliphatic and aromatic fused-ring systems) which are either hardly metabolisable or not at all. An important factor in soils or at other contaminated sites is that some of the substrate is not available because it is bound to the matrix thus increasing the proportion of residue. The next task after examining and presenting the causes of incomplete decomposition is to minimise residual mineral oil concentrations remaining after microbial decomposition. Here the use of special surfactants or of auxiliary substrates could point a way. Project applications to this end have already been submitted to the Federal Ministry for Education and Research. (orig.) [Deutsch] Dass Mikroorganismen in der Lage sind, Mineraloele zu verwerten, ist seit langem bekannt. Verfahren, die das Potential autochthoner Mikroorganismen zur Verwertung von Mineraloelen nutzen sind Praxis. Hauptproblem beim mikrobiellen Abbau der Kohlenwasserstoffe ist das Verbleiben von Mineraloelresten. Das Ziel des Forschungsvorhabens war die Ermittlung der Grenzen

  18. Response of Plasmodium falciparum to cotrimoxazole therapy: relationship with plasma drug concentrations and dihydrofolate reductase and dihydropteroate synthase genotypes

    DEFF Research Database (Denmark)

    Khalil, Insaf F; Rønn, Anita M; Alifrangis, Michael

    2005-01-01

    treatment and at days 3, 7, and 14 or upon recrudescence to ascertain drug absorption. Forty patients (89%) had an adequate clinical response, one patient (2%) had an early treatment failure response, while four patients (8%) showed late treatment failure responses. Genotyping of merozoite surface protein 1......, MSP-1, MSP-2, and glutamate-rich protein before treatment and upon recrudescence showed that all recurring parasites were recrudescences. The plasma levels of TRM, AcSMX, and SMX indicated adequate drug absorption in all patients. This suggests parasite resistance as a cause of treatment failure...

  19. Short communication: Macrocyclic lactone residues in butter from Brazilian markets.

    Science.gov (United States)

    Macedo, Fabio; Marsico, Eliane Teixeira; Conte-Júnior, Carlos Adam; de Almeida Furtado, Leonardo; Brasil, Taila Figueredo; Pereira Netto, Annibal Duarte

    2015-06-01

    Macrocyclic lactones (ML) are commonly used in drug formulations for the treatment of parasites in cattle. In Brazil, except for drugs (or formulations) with long-term (half-life) effects, ML are registered for use in bovines. Indiscriminate use of ML may result in the presence of residues in milk and dairy products due to their lipophilic properties and thermal stability. This study applied a method of liquid chromatography with fluorimetric detection, recently developed and validated for the determination of residues of abamectin, doramectin, ivermectin, and moxidectin in butter. The method was applied to 38 samples of commercial butter purchased in the metropolitan area of Rio de Janeiro, Brazil, between June and September 2013, analyzed in triplicate. Ivermectin was detected in 89.5% of the samples, with concentrations between 0.3 and 119.4 µg/kg; 76.3% of the samples contained doramectin (0.6 to 64.7 µg/kg) and 55.2% contained abamectin (0.7 to 4.5 µg/kg). Most butter samples (76.3%) contained residues of more than 1 ML; however, no residues of moxidectin were detected. The results showed a high incidence of the presence of avermectins in butter samples. Butter is not included in the Brazilian National Plan for Control of Residues and Contaminants in Animal Products. As ML residues concentrate in lipophilic compounds, butter and other fatty dairy products should be screened for the presence of ML residues. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  20. The relationship between chemical concentration and odor activity value explains the inconsistency in making a comprehensive surrogate scent training tool representative of illicit drugs.

    Science.gov (United States)

    Rice, Somchai; Koziel, Jacek A

    2015-12-01

    This report highlights the importance of an individual chemical's odor impact in the olfactory identification of marijuana, cocaine, and heroin. There are small amounts of highly odorous compounds present in headspace of these drugs, with very low odor detection thresholds, that are more likely responsible for contributing to the overall odor of these drugs. Previous reports of the most abundant compounds in headspace can mislead researchers when dealing with whole odor of these drugs. Surrogate scent formulations, therefore, must match the odor impact of key compounds and not just the chemical abundance of compounds. The objective of this study was to compare odorous volatile organic compounds (VOCs) emitted from illicit drug samples of marijuana, cocaine, and heroin to surrogate smell formulations using simultaneous sensory (via human olfaction) and chemical analyses. Use of solid phase microextraction (SPME) allowed VOCs in drug headspace to be extracted and pre-concentrated on site, and analyzed by multidimensional gas chromatography-mass spectrometry-olfactometry (MDGC-MS-O). Use of MDGC-MS-O allowed for further separation of odorous compounds and simultaneous detection by the human nose of the separate odor parts that make up the total aroma of these drugs. The compounds most abundant in headspace were not the most odor impactful when ranked by odor activity values (OAVs) (defined as ratio of concentration to odor detection threshold, ODT). There were no apparent correlations between concentrations and OAVs. A 1g marijuana surrogate lacked in odor active acids, aldehydes, ethers, hydrocarbons, N-containing, and S-containing VOCs and was overabundant in odor active alcohols and aromatics compared with real marijuana. A 1g cocaine surrogate was overabundant in odor active alcohols, aldehydes, aromatics, esters, ethers, halogenates, hydrocarbons, ketones and N-containing compounds compared with real. A 1g heroin surrogate should contain less odor active acids

  1. 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

  2. Multi-residue analysis of pesticides, plant hormones, veterinary drugs and mycotoxins using HILIC chromatography - MS/MS in various food matrices.

    Science.gov (United States)

    Danezis, G P; Anagnostopoulos, C J; Liapis, K; Koupparis, M A

    2016-10-26

    One of the recent trends in Analytical Chemistry is the development of economic, quick and easy hyphenated methods to be used in a field that includes analytes of different classes and physicochemical properties. In this work a multi-residue method was developed for the simultaneous determination of 28 xenobiotics (polar and hydrophilic) using hydrophilic interaction liquid chromatography technique (HILIC) coupled with triple quadrupole mass spectrometry (LC-MS/MS) technology. The scope of the method includes plant growth regulators (chlormequat, daminozide, diquat, maleic hydrazide, mepiquat, paraquat), pesticides (cyromazine, the metabolite of the fungicide propineb PTU (propylenethiourea), amitrole), various multiclass antibiotics (tetracyclines, sulfonamides quinolones, kasugamycin and mycotoxins (aflatoxin B1, B2, fumonisin B1 and ochratoxin A). Isolation of the analytes from the matrix was achieved with a fast and effective technique. The validation of the multi-residue method was performed at the levels: 10 μg/kg and 100 μg/kg in the following representative substrates: fruits-vegetables (apples, apricots, lettuce and onions), cereals and pulses (flour and chickpeas), animal products (milk and meat) and cereal based baby foods. The method was validated taking into consideration EU guidelines and showed acceptable linearity (r ≥ 0.99), accuracy with recoveries between 70 and 120% and precision with RSD ≤ 20% for the majority of the analytes studied. For the analytes that presented accuracy and precision values outside the acceptable limits the method still is able to serve as a semi-quantitative method. The matrix effect, the limits of detection and quantification were also estimated and compared with the current EU MRLs (Maximum Residue Levels) and FAO/WHO MLs (Maximum Levels) or CXLs (Codex Maximum Residue Limits). The combined and expanded uncertainty of the method for each analyte per substrate, was also estimated. Copyright © 2016 Elsevier B

  3. Residual risk

    African Journals Online (AJOL)

    ing the residual risk of transmission of HIV by blood transfusion. An epidemiological approach assumed that all HIV infections detected serologically in first-time donors were pre-existing or prevalent infections, and that all infections detected in repeat blood donors were new or incident infections. During 1986 - 1987,0,012%.

  4. Clinical Response to Donepezil in Mild and Moderate Dementia: Relationship to Drug Plasma Concentration and CYP2D6 and APOE Genetic Polymorphisms.

    Science.gov (United States)

    Miranda, Luís F J R; Gomes, Karina B; Tito, Pedro A L; Silveira, Josianne N; Pianetti, Gerson A; Byrro, Ricardo M D; Peles, Patrícia R H; Pereira, Fernando H; Santos, Thiago R; Assini, Arthur G; Ribeiro, Valéria V; Moraes, Edgar N; Caramelli, Paulo

    2017-01-01

    The clinical response to donepezil in patients with mild and moderate dementia was investigated in relation to the drug plasma concentration and APOE and CYP2D6 polymorphisms. In a prospective naturalistic observational study, 42 patients with Alzheimer's disease (AD) and AD with cerebrovascular disease who took donepezil (10 mg) for 12 months were evaluated. Their DNA was genotyped, and the donepezil plasma concentrations were measured after 3, 6, and 12 months. Good responders scored ≥-1 on the Mini-Mental State Examination at 12 months in comparison to the baseline score. The study results indicated the good response pattern was influenced by the concentration of donepezil, but not by APOE and CYP2D6 polymorphisms.

  5. Thermal stability of antiparasitic macrocyclic lactones milk residues during industrial processing.

    Science.gov (United States)

    Imperiale, F A; Farias, C; Pis, A; Sallovitz, J M; Lifschitz, A; Lanusse, C

    2009-01-01

    The chemical stability of residues of different antiparasitic macrocyclic lactone compounds in milk subjected to thermal treatment was assessed. Concentrations of ivermectin (IVM), moxidectin (MXD) and eprinomectin (EPM) in sheep milk, equivalent to those measured in vivo in milk excretion studies, were subjected to 65 degrees C over 30 min or to 75 degrees C for 15 s. Residue concentrations of IVM, MXD and EPM in milk were measured by high-performance liquid chromatography (HPLC) (fluorescence detection) before and after heat treatment of the drug-fortified milk samples. No evidence of chemical loss was obtained in either of the thermal treatments under evaluation. The stability of the parent compounds in milk was evidenced by the lack of bioconversion products (metabolites) after both thermal treatments. Only very minor changes on drug concentrations were observed at the end of the treatments, which fell within the limits of the variation of the validated analytical method. In conclusion, residue concentrations of macrocyclic lactones are unaffected by industrial-simulated milk thermal procedures. Based on the reported findings, it can be postulated that residue concentrations of IVM, MXD and EPM measured in raw sheep milk may be used to estimate consumer exposure and dietary intake for these veterinary drugs.

  6. 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

  7. 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

  8. Application of a hybrid ordered mesoporous silica as sorbent for solid-phase multi-residue extraction of veterinary drugs in meat by ultra-high-performance liquid chromatography coupled to ion-trap tandem mass spectrometry.

    Science.gov (United States)

    Casado, Natalia; Morante-Zarcero, Sonia; Pérez-Quintanilla, Damián; Sierra, Isabel

    2016-08-12

    A quick, sensitive and selective analytical reversed-phase multi-residue method using ultra-high performance liquid chromatography coupled to an ion-trap mass spectrometry detector (UHPLC-IT-MS/MS) operating in both positive and negative ion mode was developed for the simultaneous determination of 23 veterinary drug residues (β-blockers, β-agonists and Non-Steroidal Anti-inflammatory Drugs (NSAIDs)) in meat samples. The sample treatment involved a liquid-solid extraction followed by a solid-phase extraction (SPE) procedure. SBA-15 type mesoporous silica was synthetized and modified with octadecylsilane, and the resulting hybrid material (denoted as SBA-15-C18) was applied and evaluated as SPE sorbent in the purification of samples. The materials were comprehensively characterized, and they showed a high surface area, high pore volume and a homogeneous distribution of the pores. Chromatographic conditions and extraction procedure were optimized, and the method was validated according to the Commission Decision 2002/657/EC. The method detection limits (MDLs) and the method quantification limits (MQLs) were determined for all the analytes in meat samples and found to range between 0.01-18.75μg/kg and 0.02-62.50μg/kg, respectively. Recoveries for 15 of the target analytes ranged from 71 to 98%. In addition, for comparative purpose SBA-15-C18 was evaluated towards commercial C18 amorphous silica. Results revealed that SBA-15-C18 was clearly more successful in the multi-residue extraction of the 23 mentioned analytes with higher recovery values. The method was successfully tested to analyze prepacked preparations of mince bovine meat. Traces of propranolol, ketoprofen and diclofenac were detected in some samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Estimation of residue depletion of cyadox and its marker residue in edible tissues of pigs using physiologically based pharmacokinetic modelling.

    Science.gov (United States)

    Huang, Lingli; Lin, Zhoumeng; Zhou, Xuan; Zhu, Meiling; Gehring, Ronette; Riviere, Jim E; Yuan, Zonghui

    2015-01-01

    Physiologically based pharmacokinetic (PBPK) models are powerful tools to predict tissue distribution and depletion of veterinary drugs in food animals. However, most models only simulate the pharmacokinetics of the parent drug without considering their metabolites. In this study, a PBPK model was developed to simultaneously describe the depletion in pigs of the food animal antimicrobial agent cyadox (CYA), and its marker residue 1,4-bisdesoxycyadox (BDCYA). The CYA and BDCYA sub-models included blood, liver, kidney, gastrointestinal tract, muscle, fat and other organ compartments. Extent of plasma-protein binding, renal clearance and tissue-plasma partition coefficients of BDCYA were measured experimentally. The model was calibrated with the reported pharmacokinetic and residue depletion data from pigs dosed by oral gavage with CYA for five consecutive days, and then extrapolated to exposure in feed for two months. The model was validated with 14 consecutive day feed administration data. This PBPK model accurately simulated CYA and BDCYA in four edible tissues at 24-120 h after both oral exposure and 2-month feed administration. There was only slight overestimation of CYA in muscle and BDCYA in kidney at earlier time points (6-12 h) when dosed in feed. Monte Carlo analysis revealed excellent agreement between the estimated concentration distributions and observed data. The present model could be used for tissue residue monitoring of CYA and BDCYA in food animals, and provides a foundation for developing PBPK models to predict residue depletion of both parent drugs and their metabolites in food animals.

  10. Drug residues store in the body following cessation of use: impacts on neuroendocrine balance and behavior--use of the Hubbard sauna regimen to remove toxins and restore health.

    Science.gov (United States)

    Cecchini, Marie; LoPresti, Vincent

    2007-01-01

    For decades, scientists have investigated the environmental and human health effects of synthetic chemicals. A growing body of research has illuminated the spectrum of consequences deriving from our reliance these substances and their proliferation in air, water, soil and the food chain. Of particular concern is the fact that residues of many man-made chemicals are now detectible in virtually every person. A key to a chemical's tendency to persist in tissues once it has entered the body is its lipophilicity. Substances that are poorly soluble in water and quite soluble in fat have relatively free access, via lipid-rich cellular membranes, to the cells of all organs including the ability to cross the blood-brain and placental barriers. Substantial data exist demonstrating that in addition to pollutants, drugs and their metabolites dispose to tissues high in fat content, including brain and adipose. While their characteristic lipophilicity permits drugs and medications to reach target tissues, thereby producing therapeutic effects in the present, current perceptions of risk may be ignoring the possibility that adipose accumulations of illicit drugs and pharmaceuticals may lead to future patterns of ill health similar to those associated with exposure to other categories of xenobiotic chemicals. Empirical data are beginning to characterize the myriad regulatory functions of adipose hormones, including roles in cravings, cognitive function, energy level, and inflammation as well as changes in adipose hormone levels associated with drug use. Included in this data are the observation that a rehabilitative treatment intervention introduced by L. Ron Hubbard in 1978 to aid in the broad elimination of chemicals from body stores improves symptoms common to both chemical exposure and drug addiction. The regimen, which includes exercise, sauna bathing, and vitamin and mineral supplementation, is utilized by nearly 70 drug rehabilitation and medical practices in over 20

  11. Risk factors for virological failure and subtherapeutic antiretroviral drug concentrations in HIV-positive adults treated in rural northwestern Uganda

    Directory of Open Access Journals (Sweden)

    Ahoua Laurence

    2009-06-01

    Full Text Available Abstract Background Little is known about immunovirological treatment outcomes and adherence in HIV/AIDS patients on antiretroviral therapy (ART treated using a simplified management approach in rural areas of developing countries, or about the main factors influencing those outcomes in clinical practice. Methods Cross-sectional immunovirological, pharmacological, and adherence outcomes were evaluated in all patients alive and on fixed-dose ART combinations for 24 months, and in a random sample of those treated for 12 months. Risk factors for virological failure (>1,000 copies/ml and subtherapeutic antiretroviral (ARV concentrations were investigated with multiple logistic regression. Results At 12 and 24 months of ART, 72% (n = 701 and 70% (n = 369 of patients, respectively, were alive and in care. About 8% and 38% of patients, respectively, were diagnosed with immunological failure; and 75% and 72% of patients, respectively, had undetectable HIV RNA (1,000 copies/ml were poor adherence, tuberculosis diagnosed after ART initiation, subtherapeutic NNRTI concentrations, general clinical symptoms, and lower weight than at baseline. About 14% of patients had low ARV plasma concentrations. Digestive symptoms and poor adherence to ART were risk factors for low ARV plasma concentrations. Conclusion Efforts to improve both access to care and patient management to achieve better immunological and virological outcomes on ART are necessary to maximize the duration of first-line therapy.

  12. Residual basins

    International Nuclear Information System (INIS)

    D'Elboux, C.V.; Paiva, I.B.

    1980-01-01

    Exploration for uranium carried out over a major portion of the Rio Grande do Sul Shield has revealed a number of small residual basins developed along glacially eroded channels of pre-Permian age. Mineralization of uranium occurs in two distinct sedimentary units. The lower unit consists of rhythmites overlain by a sequence of black shales, siltstones and coal seams, while the upper one is dominated by sandstones of probable fluvial origin. (Author) [pt

  13. Life-cycle exposure of fathead minnows to environmentally relevant concentrations of the β-blocker drug propranolol.

    Science.gov (United States)

    Parrott, Joanne L; Balakrishnan, Vimal K

    2017-06-01

    Propranolol is a human pharmaceutical β-blocker that has been detected in municipal wastewater effluents at ng/L to low μg/L. To assess the potential of this compound to affect fish, fathead minnow (Pimephales promelas) were exposed for a life cycle in a flow-through system to nominal propranolol concentrations of 0.87 ng/L, 8.7 ng/L, 87 ng/L, 870 ng/L, and 8700 ng/L. Measured propranolol concentrations were below detection for the 2 lowest exposure concentrations, and were 76 ng/L, 580 ng/L, and 7800 ng/L for the 3 highest exposure concentrations. During the 162-d to 165-d exposure, no significant changes in weights or lengths were seen in fathead minnows, although the highest concentration of propranolol did cause a 15% decrease in survival of larval and juvenile stage fish compared with controls. At maturity, there were no significant changes in condition factor, liver-somatic index, or secondary sex characteristics in propranolol-exposed male or female fish. Female gonadosomatic index was significantly decreased in fish exposed to the highest concentrations of propranolol, probably because of increased egg-laying. Fathead minnows from all propranolol exposures produced more eggs than control fish, with fish exposed to 7800 ng/L propranolol producing 70% more eggs per female (p = 0.060), and having significantly increased clutch size (p = 0.008). Egg quality, % fertilization, % hatching, and % deformities in F1 fry were unaffected by propranolol exposure of fish. Propranolol exposure caused no effects in fathead minnows, except at the highest exposure concentration (7800 ng/L), where there were slight decreases in survival of juvenile minnows, and indications of increased reproduction. The present study is important because it is the first to assess the potential for effects in fish exposed to propranolol for a life cycle. Environ Toxicol Chem 2017;36:1644-1651. © 2016 SETAC. © 2016 SETAC.

  14. Monitoring the concentrations of nonsteroidal anti-inflammatory drugs and cyclooxygenase-inhibiting activities in the surface waters of the Tone Canal and Edo River Basin.

    Science.gov (United States)

    Nishi, Iwaki; Kawakami, Tsuyoshi; Onodera, Sukeo

    2015-01-01

    Environmental pollution by pharmaceuticals has become a major problem in many countries worldwide. However, little is known about the concentrations of pharmaceuticals in water sources in Japan. The objective of this study was to clarify variations in the concentrations of seven nonsteroidal anti-inflammatory drugs (NSAIDs) and in cyclooxygenase(COX)-inhibiting activities in river water and domestic wastewater collected from the Tone Canal and the Edo River Basin in Japan. Total NSAID concentrations were higher in the Tone Canal than in the Edo River, and the highest concentration was observed at the domestic wastewater inflow point located in the Tone Canal (concentration averages of salicylic acid, ibuprofen, felbinac, naproxen, mefenamic acid, diclofenac, and ketoprofen in wastewater samples were 55.3, 162.9, 39.7, 11.8, 30.8, 259.7, and 48.3 ng L(-1), respectively). Gas chromatography-tandem mass spectrometry showed that wastewater samples collected during cooler seasons contained higher levels of COX-inhibiting activity. COX-inhibiting activities were highly correlated with NSAID concentrations (particularly for ketoprofen and diclofenac); however, other COX inhibitors, such as NSAIDs that were not examined in this study and/or other chemicals with COX-inhibiting activity, could exist in the water samples because the concentrations of NSAIDs obtained from the water samples did not account for the total COX-inhibiting activities observed. Therefore, COX inhibition assays may be helpful for evaluating the aquatic toxicity of COX inhibitors. In this study, we demonstrated that COX inhibitors in surface water may influence aquatic organisms more than was expected based on NSAID concentrations. Thus, further studies examining other COX inhibitors in the aquatic environment are necessary.

  15. Statistical inference on residual life

    CERN Document Server

    Jeong, Jong-Hyeon

    2014-01-01

    This is a monograph on the concept of residual life, which is an alternative summary measure of time-to-event data, or survival data. The mean residual life has been used for many years under the name of life expectancy, so it is a natural concept for summarizing survival or reliability data. It is also more interpretable than the popular hazard function, especially for communications between patients and physicians regarding the efficacy of a new drug in the medical field. This book reviews existing statistical methods to infer the residual life distribution. The review and comparison includes existing inference methods for mean and median, or quantile, residual life analysis through medical data examples. The concept of the residual life is also extended to competing risks analysis. The targeted audience includes biostatisticians, graduate students, and PhD (bio)statisticians. Knowledge in survival analysis at an introductory graduate level is advisable prior to reading this book.

  16. 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.

  17. Intrapartum tenofovir and emtricitabine reduces low-concentration drug resistance selected by single-dose nevirapine for perinatal HIV prevention.

    Science.gov (United States)

    Chi, Benjamin H; Ellis, Giovanina M; Chintu, Namwinga; Cantrell, Ronald A; Sinkala, Moses; Aldrovandi, Grace M; Warrier, Ranjit; Mbewe, Felistas; Nakamura, Kyle; Stringer, Elizabeth M; Frenkel, Lisa M; Stringer, Jeffrey S A

    2009-11-01

    A single dose of tenofovir/emtricitabine (TDF/FTC) during labor significantly reduces peripartum nevirapine-associated viral drug resistance when measured by consensus HIV sequencing. It is unknown whether this effect extends to HIV subpopulations of or = 2% of the viral population, we used an oligonucleotide ligation assay (OLA) at codons 103, 106, 181, and 190 of HIV reverse transcriptase. To assess development of drug resistance mutations to our study intervention, OLA was also performed at codons 65 and 184. Among the 328 women included in the 2-week analysis, those receiving TDF/FTC were less likely to have NNRTI resistance by OLA (RR = 0.40, 95% CI = 0.21-0.77). A similar trend was observed among the 315 women included in the 6-week analysis (RR = 0.45, 95% CI = 0.31-0.66). Only two (1%) specimens had detectable K65R by OLA. Both were at 6 weeks postpartum; one was detected in the intervention arm and one in the control arm (p = 0.96). M184V was not detected. The ability of single-dose TDF/FTC to protect against peripartum NVP-induced NNRTI resistance extends to minority populations. This efficacy is achieved without significant selection of TDF- or FTC-resistant viruses.

  18. Dietary exposure to tetracycline residues through milk consumption in Iran.

    Science.gov (United States)

    Aalipour, Fathollah; Mirlohi, Maryam; Jalali, Mohammad; Azadbakht, Leila

    2015-01-01

    The abundant use of tetracycline antibiotics in veterinary medicine may result in the presence of their residues in milk at unsafe concentrations that can adversely affect public health. The aim of the current study was to evaluate the risk of tetracycline residue (TET) intake via milk consumption amongst different age groups of human consumers in Iran. To quantify the drug residues, HPLC analysis was performed under isocratic conditions using UV detection at 355 nm. Milk consumption patterns were determined using a recent nutrition survey in Iran. The average concentration of total TETs in milk was determined to be 252.41 μg/kg, which is approximately 2.5 times greater than the maximum residue limit (MRL) set by codex. Of the four different tetracycline antibiotics analyzed, oxytetracyclin had the highest share (86 %) of the determined contamination. Daily exposure to TETs through milk using an average data on milk consumption was estimated to range from 58-62 μg. but, distribution based exposure to TETs in milk appeared as 0-99.3 μg per day. Risk characterization of dietary exposure to TETs residue via milk intake in different age groups showed that considering the standard dietary recommendation that advices on two servings of milk per day (480 ml), consumers may receive 7-30 % of the determined ADI via bovine milk consumption.

  19. Effects of SULT1A1 Copy Number Variation on Estrogen Concentration and Tamoxifen-Associated Adverse Drug Reactions in Premenopausal Thai Breast Cancer Patients: A Preliminary Study.

    Science.gov (United States)

    Charoenchokthavee, Wanaporn; Ayudhya, Duangchit Panomvana Na; Sriuranpong, Virote; Areepium, Nutthada

    2016-01-01

    Tamoxifen is a pharmacological estrogen inhibitor that binds to the estrogen receptor (ER) in breast cells. However, it shows an estrogenic effect in other organs, which causes adverse drug reactions (ADRs). The sulfotransferase 1A1 (SULT1A1) enzyme encoded by the SULT1A1 gene is involved in estrogen metabolism. Previous research has suggested that the SULT1A1 copy number is linked with the plasma estradiol (E2) concentration. Here, a total of 34 premenopausal breast cancer patients, selected from the Thai Tamoxifen (TTAM) Project, were screened for their SULT1A1 copy number, plasma E2 concentration and ADRs. The mean age was 44.3±11.1 years, and they were subtyped as ER+/ progesterone receptor (PR) + (28 patients), ER+/ PR- (5 patients) and ER-/PR- (1 patient). Three patients reported ADRs, which were irregular menstruation (2 patients) and vaginal discharge (1 patient). Most (33) patients had two SULT1A1 copies, with one patient having three copies. The median plasma E2 concentration was 1,575.6 (IQR 865.4) pg/ml. Patients with ADRs had significantly higher plasma E2 concentrations than those patients without ADRs (p = 0.014). The plasma E2 concentration was numerically higher in the patient with three SULT1A1 copies, but this lacked statistical significance.

  20. 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

  1. Viability of primary osteoblasts after treatment with tenofovir alafenamide: Lack of cytotoxicity at clinically relevant drug concentrations.

    Directory of Open Access Journals (Sweden)

    Christian Callebaut

    Full Text Available Tenofovir alafenamide (TAF is a phosphonoamidate prodrug of the nucleotide HIV reverse transcriptase inhibitor tenofovir (TFV. TAF is approved for the treatment of HIV-1 infection as part of the single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF. When dosed once-daily, TAF results in approximately 90% lower levels of plasma TFV and a 4-fold increase in intracellular TFV-diphosphate (TFV-DP in PBMCs compared with the TFV prodrug tenofovir disoproxil fumarate (TDF. Several antiretrovirals, including TDF, have been associated with bone mineral density decreases in patients; the effect of clinically relevant TAF concentrations on primary osteoblast viability was therefore assessed in vitro. Studies in PBMCs determined that a 2-hour TAF exposure at concentrations similar to human plasma Cmax achieved intracellular TFV-DP levels comparable to those observed after the maximum recommended human dose of 25 mg TAF. Comparable intracellular TFV-DP levels were achieved in primary osteoblasts with 2-hour TAF exposure daily for 3 days at concentrations similar to those used for PBMCs (100-400 nM. No change in cell viability was observed in either primary osteoblasts or PBMCs. The mean TAF CC50 in primary osteoblasts after 3 days of daily 2-hour pulses was >500 μM, which is >1033 times higher than the TAF maximum recommended human dose plasma Cmax. In summary, primary osteoblasts were not preferentially loaded by TAF compared with PBMCs, with comparable TFV-DP levels achieved in both cell types. Furthermore, there was no impact on osteoblast cell viability at clinically relevant TAF concentrations.

  2. Antimicrobial residues screening in pigs and goats slaughtered in ...

    African Journals Online (AJOL)

    Ekene Vivienne Ezenduka

    2012-07-17

    Jul 17, 2012 ... Antimicrobial residue in animal food products is an important index of food safety. Drug residues could result from chemotherapeutic or chemoprophylactic use of drugs in food animals. This occurrence of residue in animal food products has received enormous worldwide attention from some local, ...

  3. Second research coordination meeting of the coordinated research project 'Development of strategies for the effective monitoring of veterinary drug residues in livestock and livestock products in developing countries' (D3.20.22)

    International Nuclear Information System (INIS)

    2003-01-01

    The second RCM under this CRP was held in Pretoria, South Africa, 3 - 7 November 2003. Eleven of the twelve research contract holders, three research agreement holders and one technical contract holder attended the RCM. The three research agreement holders gave presentations on relevant aspects of veterinary drug residues analysis. The increasingly important role of bioassay techniques such as reporter gene assays for the direct screening of the effects of hormonal and other residues in animal cells and the future role of such assays to complement existing instrumental techniques was highlighted. The technical contract holder and research contract holders reviewed the results of the research and method development performed under the first phase of the CRP. Considerable progress has been made in many aspects of the overall work plan. Several commercial immunoassay methods have been critically evaluated. The main problems identified with these kits were the instability of reagents, notably the enzyme conjugates, resulting in poor performance, and the need for better sample preparation protocols applicable to a wider range of matrices. Work plans have been agreed with several laboratories to attempt to address these problems. Good progress has been made in several laboratories working on the development of in-house ELISA methods for chloramphenicol residues. The laboratories involved have produced and characterized antisera in various species and these will be used with reagents produced by technical contract holders to elaborate assay protocols. Further investigation into aspects such as reagent stability, antibody maturation and assay development using various assay formats is planned. A full set of reagents and protocols for their optimisation in a 125 I radioimmunoassay (RIA) for chloramphenicol have been developed by the technical contract holders and transferred to a research contract holder for further method development. However, this researcher was unable to

  4. 3D modeling of effects of increased oxygenation and activity concentration in tumors treated with radionuclides and antiangiogenic drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lagerloef, Jakob H.; Kindblom, Jon; Bernhardt, Peter [Department of Radiation Physics, Goeteborg University, Goeteborg 41345 (Sweden); Department of Oncology, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden); Department of Radiation Physics, Goeteborg University, Goeteborg, Sweden and Department of Nuclear Medicine, Sahlgrenska University Hospital, Goeteborg 41345 (Sweden)

    2011-08-15

    Purpose: Formation of new blood vessels (angiogenesis) in response to hypoxia is a fundamental event in the process of tumor growth and metastatic dissemination. However, abnormalities in tumor neovasculature often induce increased interstitial pressure (IP) and further reduce oxygenation (pO{sub 2}) of tumor cells. In radiotherapy, well-oxygenated tumors favor treatment. Antiangiogenic drugs may lower IP in the tumor, improving perfusion, pO{sub 2} and drug uptake, by reducing the number of malfunctioning vessels in the tissue. This study aims to create a model for quantifying the effects of altered pO{sub 2}-distribution due to antiangiogenic treatment in combination with radionuclide therapy. Methods: Based on experimental data, describing the effects of antiangiogenic agents on oxygenation of GlioblastomaMultiforme (GBM), a single cell based 3D model, including 10{sup 10} tumor cells, was developed, showing how radionuclide therapy response improves as tumor oxygenation approaches normal tissue levels. The nuclides studied were {sup 90}Y, {sup 131}I, {sup 177}Lu, and {sup 211}At. The absorbed dose levels required for a tumor control probability (TCP) of 0.990 are compared for three different log-normal pO{sub 2}-distributions: {mu}{sub 1} = 2.483, {sigma}{sub 1} = 0.711; {mu}{sub 2} = 2.946, {sigma}{sub 2} = 0.689; {mu}{sub 3} = 3.689, and {sigma}{sub 3} = 0.330. The normal tissue absorbed doses will, in turn, depend on this. These distributions were chosen to represent the expected oxygen levels in an untreated hypoxic tumor, a hypoxic tumor treated with an anti-VEGF agent, and in normal, fully-oxygenated tissue, respectively. The former two are fitted to experimental data. The geometric oxygen distributions are simulated using two different patterns: one Monte Carlo based and one radially increasing, while keeping the log-normal volumetric distributions intact. Oxygen and activity are distributed, according to the same pattern. Results: As tumor pO{sub 2

  5. Residues of sulfadiazine and doxycycline in broiler liver and muscle tissue due to cross-contamination of feed.

    Science.gov (United States)

    Vandenberge, V; Delezie, E; Huyghebaert, G; Delahaut, P; Daeseleire, E; Croubels, S

    2012-01-01

    Veterinary drugs, such as antimicrobial compounds, are widely used in poultry and may lead to the presence of residues in matrices of animal origin, such as muscle and liver tissue. In this study, broilers received an experimental feed containing sulfadiazine or doxycycline at cross-contamination levels of 2.5, 5 and 10% of the therapeutic dose in feed. Breast and thigh muscle and liver samples were collected during treatment and depletion period and analysed via liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations reached a plateau phase 3-5 days after the start of experimental feeding. A rapid depletion of residues was noted after withdrawal of the experimental feed. No significant differences in measured concentrations were observed between the various muscle types. Residue concentrations for some experimental groups; the 10% group of sulfadiazine and the 5 and 10% group of doxycycline, however, exceeded their corresponding maximum residue limits (MRLs).

  6. The law of mass action and the pharmacological concentration-effect curve: resolving the paradox of apparently non-dose-related adverse drug reactions.

    Science.gov (United States)

    Aronson, Jeffrey K; Ferner, Robin E

    2016-01-01

    Adverse drug reactions are sometimes described as being 'non-dose-related' because no relationship has been found between increasing doses and either the intensity of the response or the proportion of individuals in whom the response occurs; furthermore, hypersensitivity reactions are often regarded as being non-dose-related, even if different doses have not been studied. However, the law of mass action implies that all pharmacological effects are concentration related and should increase in intensity with increasing dose. We set out to explain this paradox. We searched for published adverse drug reactions that have been described as non-dose-related and analysed them. We identified four categories of explanations that resolve the paradox: (i) the reaction is not real; it may have occurred by chance or there may be methodological problems, such as bias or confounding factors; (ii) the dose-response curve for the adverse effect reaches a maximum at doses lower than were studied (i.e. a hypersusceptibility reaction); this underpins the use of test doses to predict the possibility of an adverse reaction at therapeutic doses; (iii) susceptibility to the adverse reaction differs widely among individuals; and (iv) imprecision or inaccuracy in the measurement of either dose or effect obscures dose responsiveness. This last explanation encompasses: (a) reactions related to cumulative dose; (b) dissociation between dose and concentration through saturable pharmacokinetics; and (c) variability in the measurement of the effect. If an adverse drug reaction appears to be non-dose-related, the reasons should be sought, having these mechanisms in mind. © 2015 The British Pharmacological Society.

  7. RESIDUAL RISK ASSESSMENTS - RESIDUAL RISK ...

    Science.gov (United States)

    This source category previously subjected to a technology-based standard will be examined to determine if health or ecological risks are significant enough to warrant further regulation for Coke Ovens. These assesments utilize existing models and data bases to examine the multi-media and multi-pollutant impacts of air toxics emissions on human health and the environment. Details on the assessment process and methodologies can be found in EPA's Residual Risk Report to Congress issued in March of 1999 (see web site). To assess the health risks imposed by air toxics emissions from Coke Ovens to determine if control technology standards previously established are adequately protecting public health.

  8. 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

  9. Wide-scope analysis of pesticide and veterinary drug residues in meat matrices by high resolution MS: detection and identification using Exactive-Orbitrap.

    Science.gov (United States)

    Gómez-Pérez, María Luz; Romero-González, Roberto; Plaza-Bolaños, Patricia; Génin, Eric; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2014-01-01

    A multiresidue and multiclass method for the simultaneous determination of more than 350 compounds including pesticides, biopesticides and veterinary drugs in different meat matrices (beef, pork and chicken) by ultra-high performance liquid chromatography coupled to Orbitrap MS has been developed. In the present study, the determination of fragments was accomplished as an essential tool for a reliable identification of compounds using high resolution MS. To obtain these fragments, different strategies have been carried out in order to ensure an appropriate fragment assignment and identification. The analytical method is suitable for qualitative analysis, and it was also evaluated for quantitative analysis. Generic extraction conditions were optimized, obtaining adequate recovery and precision values for most of the studied analytes (>290). The limits of detection ranged from 2 to 16 µg kg(-1). Limits of quantification were 10 µg kg(-1) with the exception of few compounds with a higher value (50 or 100 µg kg(-1)). Limits of identification were also established, and they ranged from 2 to 150 µg kg(-1). This method was applied to the analysis of 18 meat samples and some veterinary drugs as enrofloxacin and sulfadiazine were detected and further identified/quantified (with triple quadrupole) in two different samples at 33 µg kg(-1) and trace levels, respectively. No pesticides were detected in the analyzed samples. Copyright © 2014 John Wiley & Sons, Ltd.

  10. Significance of higher drug concentration in erythrocytes of mice infected with Schistosoma japonicum and treated orally with mefloquine at single doses.

    Science.gov (United States)

    Tao, Yi; Xue, Jian; Jiang, Bin; Zhang, Hao-Bing; Xiao, Shu-Hua

    2015-12-01

    The purpose of the present study is to understand the pharmacokinetic feature of mefloquine measured by erythrocytes and plasma in Schistosoma japonicum (S. j.)-infected mice and non-infected mice after oral administration of the drug at single doses. A high-performance liquid chromatography (HPLC) method was used to measure the plasma and erythrocyte concentrations of mefloquine at varying intervals posttreatment. Our results demonstrated that in non-infected mice treated orally with mefloquine at an ineffective dose of 50 mg/kg or effective dose of 200 mg/kg for 2-72 h, the erythrocyte-to-plasma ratios of mefloquine were 5.8-11.2 or 2-14.2. On the other hand, in S. j.-infected mice treated with the same single doses of the drug, the erythrocyte and plasma drug concentration ratios were 3.1-4.6 or 2.9-8.5, manifesting that either in infected mice or in non-infected mice that received oral mefloquine resulted in higher concentration of mefloquine in erythrocytes than that in plasma. Unexpectedly, under oral administration of mefloquine at a higher single dose of 200 mg/kg, the pharmacokinetic parameter C max values for plasma from S. j.-infected and non-infected mice were 1.6 ± 0.3 and 2.0 ± 0.4 μg/mL, respectively, which were below the determined in vitro LC50 (50 % lethal concentration) value of 4.93 μg/mL. Therefore, the plasma concentration of mefloquine may display a little effect against schistosomes during the treatment. Although the values of T 1/2 and AUC0-∞ for erythrocytes were significantly longer and higher in infected mice than those of corresponding non-infect mice that received the same single mefloqine dose of 50 mg/kg, the C max value was only 2.6 ± 0.4 μg/mL lower than the determined in vitro LC50, which may explain why this low single dose is ineffective against schistosomes in vivo. After administration of higher mefloquine dose of 200 mg/kg, the C max value for erythrocytes in infected mice was 30 % (7.4 ± 0

  11. High azithromycin concentration in lungs by way of bovine serum albumin microspheres as targeted drug delivery: lung targeting efficiency in albino mice.

    Science.gov (United States)

    Ramaiah, Balakeshwa; Nagaraja, Sree Harsha; Kapanigowda, Usha Ganganahalli; Boggarapu, Prakash Rao; Subramanian, Rajarajan

    2016-05-05

    Following administration, the antibiotic travels freely through the body and also accumulates in other parts apart from the infection site. High dosage and repeated ingestion of antibiotics in the treatment of pneumonia leads to undesirable effects and inappropriate disposition of the drug. By way of targeted lung delivery, this study was intended to eliminate inappropriate azithromycin disposition and to achieve higher azithromycin concentration to treat deeper airway infections. The Azithromycin Albumin Microspheres (AAM) was prepared by emulsion polymerization technique. The optimized AAM was subjected to in vitro release study, release kinetics, XRD and stability studies. Further, in vivo pharmacokinetics and tissue distribution of azithromycin released from AAM and azithromycin solution in albino mice was investigated to prove suitability of moving forward the next steps in the clinic. The mean particle size of the optimized AAM was 10.02 μm, an optimal size to get deposited in the lungs by mechanical entrapment. The maximum encapsulation efficiency of 82.3 % was observed in this study. The release kinetic was significant and best fitted for Korsmeyer-Peppas model (R(2) = 0.9962, n = 0.41). The XRD and stability study showed favorable results. Azithromycin concentration in mice lungs (40.62 μg g(-1), 30 min) of AAM was appreciably higher than other tissues and plasma. In comparison with control, azithromycin concentration in lungs was 30.15 μg g(-1) after 30 min. The azithromycin AUC (929.94 μg h mL(-1)) and intake rate (re) (8.88) for lung were higher and statistically significant in AAM group. Compared with spleen and liver, the targeting efficacy (te) in mice lung increased by a factor of 40.15 and ~14.10 respectively. Subsequently by a factor of 8.94, the ratio of peak concentration (Ce) in lung was higher in AAM treated mice. The AAM lung tissue histopathology did not show any degenerative changes. High azithromycin concentration in

  12. An alkaline comet assay study on the antimalarial drug atovaquone in human peripheral blood lymphocytes: a study based on clinically relevant concentrations.

    Science.gov (United States)

    Dinter, Domagoj; Gajski, Goran; Garaj-Vrhovac, Vera

    2013-01-01

    Atovaquone, a hydroxynaphthoquinone, is an anti-parasite drug, selectively targeting the mitochondrial respiratory chain of malaria parasite. It is used for both the treatment and prevention of malaria, usually in a fixed combination with proguanil. Although atovaquone has not often been associated with severe adverse reactions in the recommended dosages and has a relatively favorable side effect profile, the present study was undertaken to evaluate its cytogenotoxic potential towards human peripheral blood lymphocytes. Two different concentrations of atovaquone found in plasma when used in fixed-dose combination with proguanile hydrochloride were used with and without S9 metabolic activation: 2950 ng ml(-1) used for prophylactic treatment and 11 800 ng ml(-1) used in treatment of malaria. The results showed that lymphocyte viability was not affected after the treatment, suggesting that atovaquone was not cytotoxic in the given concentrations. With the alkaline comet assay we demonstrated that in human peripheral blood lymphocytes no significant changes in comet parameters occurred after the treatment. There were no differences in tested parameters with the addition of S9 metabolic activation, indicating that atovaquone either has no metabolite or it is not toxic in the given concentrations. Since no effects were observed after the treatment, it is to be concluded that atovaquone is safe from the aspect of genototoxicity in the recommended dosages. Copyright © 2011 John Wiley & Sons, Ltd.

  13. Residual nilpotence and residual solubility of groups

    International Nuclear Information System (INIS)

    Mikhailov, R V

    2005-01-01

    The properties of the residual nilpotence and the residual solubility of groups are studied. The main objects under investigation are the class of residually nilpotent groups such that each central extension of these groups is also residually nilpotent and the class of residually soluble groups such that each Abelian extension of these groups is residually soluble. Various examples of groups not belonging to these classes are constructed by homological methods and methods of the theory of modules over group rings. Several applications of the theory under consideration are presented and problems concerning the residual nilpotence of one-relator groups are considered.

  14. Examining factors that influence the effectiveness of cleaning antineoplastic drugs from drug preparation surfaces: a pilot study.

    Science.gov (United States)

    Hon, Chun-Yip; Chua, Prescillia Ps; Danyluk, Quinn; Astrakianakis, George

    2014-06-01

    Occupational exposure to antineoplastic drugs has been documented to result in various adverse health effects. Despite the implementation of control measures to minimize exposure, detectable levels of drug residual are still found on hospital work surfaces. Cleaning these surfaces is considered as one means to minimize the exposure potential. However, there are no consistent guiding principles related to cleaning of contaminated surfaces resulting in hospitals to adopt varying practices. As such, this pilot study sought to evaluate current cleaning protocols and identify those factors that were most effective in reducing contamination on drug preparation surfaces. Three cleaning variables were examined: (1) type of cleaning agent (CaviCide®, Phenokil II™, bleach and chlorhexidine), (2) application method of cleaning agent (directly onto surface or indirectly onto a wipe) and (3) use of isopropyl alcohol after cleaning agent application. Known concentrations of antineoplastic drugs (either methotrexate or cyclophosphamide) were placed on a stainless steel swatch and then, systematically, each of the three cleaning variables was tested. Surface wipes were collected and quantified using high-performance liquid chromatography-tandem mass spectrometry to determine the percent residual of drug remaining (with 100% being complete elimination of the drug). No one single cleaning agent proved to be effective in completely eliminating all drug contamination. The method of application had minimal effect on the amount of drug residual. In general, application of isopropyl alcohol after the use of cleaning agent further reduced the level of drug contamination although measureable levels of drug were still found in some cases.

  15. Review of environmental exposure concentrations of chemical warfare agent residues and associated the fish community risk following the construction and completion of the Nord Stream gas pipeline between Russia and Germany.

    Science.gov (United States)

    Sanderson, Hans; Fauser, Patrik; Rahbek, Malene; Larsen, Jørn Bo

    2014-08-30

    This paper compiles all the measured chemical warfare agent (CWA) concentrations found in relation to the Nord Stream pipeline work in Danish waters for the past 5 years. Sediment and biota sampling were performed along the pipeline route in four campaigns, prior to (in 2008 and 2010), during (in 2011) and after (in 2012) the construction work. No parent CWAs were detected in the sediments. Patchy residues of CWA degradation products of Adamsite, Clark I, phenyldichloroarsine, trichloroarsine and Lewisite II, were detected in a total of 29 of the 391 sediment samples collected and analyzed the past 5 years. The cumulative fish community risk quotient for the different locations, calculated as a sum of background and added risk, ranged between 0 and 0.017 suggesting a negligible acute CWA risk toward the fish community. The added risk from sediment disturbance in relation to construction of the pipelines represents less than 2% of the total risk in the areas with the highest calculated risk. The analyses of benthic infauna corroborate the finding of CWA related low risk across the years. There was no significant difference in CWA risk before (2008) and after the pipeline construction (2012). Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Control of the Kanzawa Spider Mite, Tetranychus kanzawai Kishida and Pink Tea Rust Mite, Acaphylla theavagrans Kadono and the Residual Effect of Spraying Petroleum Oil Emulsifiable Concentrate just before the Sprouting of the First Crop of Tea

    Science.gov (United States)

    Yoshioka, Tetsuya; Sakaida, Teruki; Nakazono, Kentaro; Nitabaru, Yuichi

    Petroleum oil emulsifiable concentrate (POEC) is a commercial acaricide used for the control of Tetranychus kanzawai Kishida in the autumn/winter season. Further, the damage of bacterial shoot blight increases if POEC is sprayed at this time of the year. It is thought that the occurrence of bacterial shoot blight doesn't increase if POEC is sprayed just before the sprouting of the first crop of tea. However, it is suspected that spraying of POEC at this time results in the formation of an oily film that floats on the surface of tea infusion. In this study, we examined the efficiency of spraying POEC at this time of the year in controlling the growth of T. kanzawai and Acaphylla theavagrans Kadono and the residual effect. We obtained the following results: (1) spraying POEC before sprouting of the first crop of tea resulted in effective control of the density of T. kanzawai and A. theavagrans for 1 month or longer, and (2) the oily film was not observed on the surface of the tea infusion. These results indicate that POEC can serve as one of the important control agents of mites when sprayed just before the sprouting of the first crop of tea.

  17. Validation of an HPLC–UV method for the determination of digoxin residues on the surface of manufacturing equipment

    Directory of Open Access Journals (Sweden)

    ZORAN B. TODOROVIĆ

    2009-09-01

    Full Text Available In the pharmaceutical industry, an important step consists in the removal of possible drug residues from the involved equipments and areas. The cleaning procedures must be validated and methods to determine trace amounts of drugs have, therefore, to be considered with special attention. An HPLC–UV method for the determination of digoxin residues on stainless steel surfaces was developed and validated in order to control a cleaning procedure. Cotton swabs, moistened with methanol were used to remove any residues of drugs from stainless steel surfaces, and give recoveries of 85.9, 85.2 and 78.7 % for three concentration levels. The precision of the results, reported as the relative standard deviation (RSD, were below 6.3 %. The method was validated over a concentration range of 0.05–12.5 µg mL-1. Low quantities of drug residues were determined by HPLC–UV using a Symmetry C18 column (150´4.6 mm, 5 µm at 20 °C with an acetonitrile–water (28:72, v/v mobile phase at a flow rate of 1.1 mL min-1, an injection volume of 100 µL and were detected at 220 nm. A simple, selective and sensitive HPLC–UV assay for the determination of digoxin residues on stainless steel was developed, validated and applied.

  18. Evaluation of chloramphenicol residues in poultry meat using ELISA method in Isfahan

    Directory of Open Access Journals (Sweden)

    E Rahimi

    2008-11-01

    Full Text Available Chloramphenicol is classified as a broad spectrum veterinary drugs used to treat pulmonary infections in the poultry industry. Even relatively low levels of chloramphenicol residues may give rice to an irreversible type of bone marrow depression leading eventually to anaplastic anemia. This study was conducted with the aim of chicken meat. Chloramphenicol concentraction was measured by enzyme (ELISA in 140 chicken meat samples (thigh muscles presented to the consumption market of isfahan city. In 25 of the 140 evaluated samples (17.9%, presence of chloramephnicol residues was detected in concentrations rouging form 14 to 311 ng/kg with a mean ±standard deviation of 97.9 ±17.7 ng/kg. the results of chloramphenicol residues were low in the samples but this drug is still being used in the poultry industry and this can be a risk to public health.

  19. Development of a multi-residue method for fast screening and confirmation of 20 prohibited veterinary drugs in feedstuffs by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Zhang, Gui-Jun; Fang, Bing-Hu; Liu, Ya-Hong; Wang, Xu-Feng; Xu, Li-Xiao; Zhang, Ya-Ping; He, Li-Min

    2013-10-01

    A simple multiresidue method was developed for detecting and quantifying twenty analytes from 5 classes of prohibited veterinary drugs (β-agonists (9), anabolic hormones (4), quinoxalines (4), tranquilizers (1), cyproheptadine, and clonidine in animal feeds using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach. Feed samples were extracted by ultrasonic-assisted extraction with a mixture of methanol-acetonitrile (50:50, v/v), followed by a cleanup using a dispersive solid-phase extraction with PSA (primary secondary amine). Target compounds were separated and determined by a liquid chromatography tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring (MRM). The recoveries of these compounds were between 56.7% and 103% at three spiked levels. The repeatability was lower than 10%, whereas reproducibility was no more than 15% except for nandrolone (17% at 10μgkg(-1)) and diazepam (19% at 10μgkg(-1)). Decision limits (CCαs) and detection capabilities (CCβs) ranged from 0.42 to 5.74μgkg(-1) and 5.70-9.81μgkg(-1), respectively. The method was successfully applied to screening of real samples obtained from local feed markets and confirmation of the suspected target analytes. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Characterisation and management of concrete grinding residuals.

    Science.gov (United States)

    Kluge, Matt; Gupta, Nautasha; Watts, Ben; Chadik, Paul A; Ferraro, Christopher; Townsend, Timothy G

    2018-02-01

    Concrete grinding residue is the waste product resulting from the grinding, cutting, and resurfacing of concrete pavement. Potential beneficial applications for concrete grinding residue include use as a soil amendment and as a construction material, including as an additive to Portland cement concrete. Concrete grinding residue exhibits a high pH, and though not hazardous, it is sufficiently elevated that precautions need to be taken around aquatic ecosystems. Best management practices and state regulations focus on reducing the impact on such aquatic environment. Heavy metals are present in concrete grinding residue, but concentrations are of the same magnitude as typically recycled concrete residuals. The chemical composition of concrete grinding residue makes it a useful product for some soil amendment purposes at appropriate land application rates. The presence of unreacted concrete in concrete grinding residue was examined for potential use as partial replacement of cement in new concrete. Testing of Florida concrete grinding residue revealed no dramatic reactivity or improvement in mortar strength.

  1. Applications of linking PBPK and PD models to predict the impact of genotypic variability, formulation differences, differences in target binding capacity and target site drug concentrations on drug responses and variability.

    Directory of Open Access Journals (Sweden)

    Manoranjenni eChetty

    2014-11-01

    Full Text Available This study aimed to demonstrate the added value of integrating prior in vitro data and knowledge-rich physiologically based pharmacokinetic (PBPK models with pharmacodynamics (PD models. Four distinct applications that were developed and tested are presented here. PBPK models were developed for metoprolol using different CYP2D6 genotypes based on in vitro data. Application of the models for prediction of phenotypic differences in the pharmacokinetics (PK and PD compared favourably with clinical data, demonstrating that these differences can be predicted prior to the availability of such data from clinical trials. In the second case, PK and PD data for an immediate release formulation of nifedipine together with in vitro dissolution data for a controlled release formulation (CR were used to predict the PK and PD of the CR. This approach can be useful to pharmaceutical scientists during formulation development. The operational model of agonism was used in the third application to describe the hypnotic effects of triazolam, and this was successfully extrapolated to zolpidem by changing only the drug related parameters from in vitro experiments. This PBPK modelling approach can be useful to developmental scientists who which to compare several drug candidates in the same therapeutic class. Finally, differences in QTc prolongation due to quinidine in Caucasian and Korean females were successfully predicted by the model using free heart concentrations as an input to the PD models. This PBPK linked PD model was used to demonstrate a higher sensitivity to free heart concentrations of quinidine in Caucasian females, thereby providing a mechanistic understanding of a clinical observation. In general, permutations of certain conditions which potentially change PK and hence PD may not be amenable to the conduct of clinical studies but linking PBPK with PD provides an alternative method of investigating the potential impact of PK changes on PD.

  2. The current status of community drug testing via the analysis of drugs and drug metabolites in sewage

    Directory of Open Access Journals (Sweden)

    Malcolm J. Reid

    2011-12-01

    Full Text Available Over the past few years the analysis of drug residues in sewage has been promoted as a means of estimating the level of drug use in communities. Measured drug residue concentrations in the sewage are used to determine the load (total mass of the drug being used by the entire community. Knowledge of the size or population of the community then allows for the calculation of drug-use relative to population (typically drug-mass/day/1000 inhabitants which facilitates comparisons between differing communities or populations. Studies have been performed in many European countries, including Norway, as well as in the US and Australia. The approach has successfully estimated the use of cocaine, amphetamine, methamphetamine, MDMA, cannabis, nicotine and alcohol. The analysis of biomarkers of drug use in sewage has great potential to support and complement existing techniques for estimating levels of drug use, and as such has been identified as a promising development by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA; www.emcdda.europa.eu/wastewater-analysis. The approach is not without its challenges, and ongoing collaboration across Europe aims at agreeing upon best-practice and harmonising the methods being used. In Norway development is being performed through the NFR RUSMIDDEL funded DrugMon (www.niva.no/drugmon project that has led to the development of many new techniques, significantly improved our understanding of the uncertainties associated with the approach and allowed the coordination of Europe wide collaboration which has included all important intercalibration exercises. Application of the technique can provide evidence-based and real-time estimates of collective drug use with the resulting data used to improve the much needed estimates of drug use and dependency.

  3. Moxidectin residues in tissues of lambs submitted to three endoparasite control programs.

    Science.gov (United States)

    Fernandes, Maria Angela Machado; Gilaverte, Susana; Bianchi, Michele Dell; da Silva, Claudio José Araujo; Molento, Marcelo Beltrão; Reyes, Felix Guillermo Reyes; Monteiro, Alda Lucia Gomes

    2017-10-01

    The indiscriminate and continuous use of anthelmintic drugs has promoted the selection of resistant parasites population, the presence of drug residues in food products, and heavy environmental contamination. The aim of the present study was to determine the presence of antiparasitic drug residues in 42-days old lamb serum and tissues, submitted to three endoparasite control programs: preventive treatment (PT) using moxidectin (MOX) at every 28days; selective treatment (FEC) using MOX when fecal egg count was greater than or equal to 700; and selective treatment (FMC), using MOX when FAMACHA/FMC score was 3 and above. For this purpose, MOX residues were quantified in serum, muscle, fat, liver and kidney. Lambs were slaughtered when reaching 30kg of body weight, and after a 28-day MOX withdrawal period. Before slaughter, blood was collected to determine the concentration of MOX in serum. Tissues and organ samples were collected at slaughter. The quantitation of MOX residues was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS). From the 756 tissue samples analyzed, only one sample of fat from the PT group showed residue levels (586.3μg/kg) above the maximum residue limit (MRL) of 500μg/kg. No treated lambs presented traces of MOX residues in fat and liver, suggesting possible environmental contamination. In conclusion, all weaned lambs, produced in continuous grazing and subjected to gastrointestinal parasite control programs via selective (FEC and FMC) or preventive (PT) treatment, displayed a low risk (residues above the MRL in muscle, fat, kidney, and liver. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Matrix solid-phase dispersion on column clean-up/pre-concentration as a novel approach for fast isolation of abuse drugs from human hair.

    Science.gov (United States)

    Míguez-Framil, Martha; Moreda-Piñeiro, Antonio; Bermejo-Barrera, Pilar; Alvarez-Freire, Iván; Tabernero, María Jesús; Bermejo, Ana María

    2010-10-08

    A simple and fast sample pre-treatment method based on matrix solid-phase dispersion (MSPD) for isolating cocaine, benzoylecgonine (BZE), codeine, morphine and 6-monoacethylmorphine (6-MAM) from human hair has been developed. The MSPD approach consisted of using alumina (1.80 g) as a dispersing agent and 0.6M hydrochloric acid (4 mL) as an extracting solvent. For a fixed hair sample mass of 0.050 g, the alumina mass to sample mass ratio obtained was 36. A previously conditioned Oasis HLB cartridge (2 mL methanol, plus 2 mL ultrapure water, plus 1 mL of 0.2M/0.2M sodium hydroxide/boric acid buffer solution at pH 9.2) was attached to the end of the MSPD syringe for on column clean-up of the hydrochloric acid extract and for transferring the target compounds to a suitable solvent for gas chromatography (GC) analysis. Therefore, the adsorbed analytes were directly eluted from the Oasis HLB cartridges with 2 mL of 2% acetic acid in methanol before concentration by N(2) stream evaporation and dry extract derivatization with N-methyl-tert-butylsilyltrifluoroacetamide (BSTFA) and chlorotrimethylsilane (TMCS). The optimization/evaluation of all the factors affecting the MSPD and on column clean-up procedures has led to a fast sample treatment, and analytes extraction and pre-concentration can be finished in approximately 30 min. The developed method has been applied to eight hair samples from poli-drug abusers and measured analyte concentrations have been found to be statistically similar (95% confidence interval) to those obtained after a conventional enzymatic hydrolysis method (Pronase E). Copyright © 2010. Published by Elsevier B.V.

  5. Towards a better prediction of peak concentration, volume of distribution and half-life after oral drug administration in man, using allometry.

    Science.gov (United States)

    Sinha, Vikash K; Vaarties, Karin; De Buck, Stefan S; Fenu, Luca A; Nijsen, Marjoleen; Gilissen, Ron A H J; Sanderson, Wendy; Van Uytsel, Kelly; Hoeben, Eva; Van Peer, Achiel; Mackie, Claire E; Smit, Johan W

    2011-05-01

    It is imperative that new drugs demonstrate adequate pharmacokinetic properties, allowing an optimal safety margin and convenient dosing regimens in clinical practice, which then lead to better patient compliance. Such pharmacokinetic properties include suitable peak (maximum) plasma drug concentration (C(max)), area under the plasma concentration-time curve (AUC) and a suitable half-life (t(½)). The C(max) and t(½) following oral drug administration are functions of the oral clearance (CL/F) and apparent volume of distribution during the terminal phase by the oral route (V(z)/F), each of which may be predicted and combined to estimate C(max) and t(½). Allometric scaling is a widely used methodology in the pharmaceutical industry to predict human pharmacokinetic parameters such as clearance and volume of distribution. In our previous published work, we have evaluated the use of allometry for prediction of CL/F and AUC. In this paper we describe the evaluation of different allometric scaling approaches for the prediction of C(max), V(z)/F and t(½) after oral drug administration in man. Twenty-nine compounds developed at Janssen Research and Development (a division of Janssen Pharmaceutica NV), covering a wide range of physicochemical and pharmacokinetic properties, were selected. The C(max) following oral dosing of a compound was predicted using (i) simple allometry alone; (ii) simple allometry along with correction factors such as plasma protein binding (PPB), maximum life-span potential or brain weight (reverse rule of exponents, unbound C(max) approach); and (iii) an indirect approach using allometrically predicted CL/F and V(z)/F and absorption rate constant (k(a)). The k(a) was estimated from (i) in vivo pharmacokinetic experiments in preclinical species; and (ii) predicted effective permeability in man (P(eff)), using a Caco-2 permeability assay. The V(z)/F was predicted using allometric scaling with or without PPB correction. The t(½) was estimated from

  6. 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

  7. Eimeria Oocyst Concentrations and Species Composition in Litter from Commercial Broiler Farms During Anticoccidial Drug or Live Eimeria Oocyst Vaccine Control Programs.

    Science.gov (United States)

    Jenkins, Mark C; Parker, Carolyn; Ritter, Donald

    2017-06-01

    The purpose of this study was to determine if Eimeria oocyst concentrations and species composition in commercial broiler house litter changed during different cycles of anticoccidial drug (ACD) or live Eimeria oocyst vaccine (VAC) control programs and if there was a correlation between Eimeria oocyst levels and broiler performance. Litter samples were collected from a total of 15 different broiler farms encompassing a total of 45 individual houses during at least one complete grow-out cycle over a 21-mo period. Of these 15 broiler farms, three were followed for the entire 21-mo period spanning three ACD and four VAC cycles. Samples were collected at 2, 4, and 7-8 wk of grow-out corresponding to starter, grower, and withdraw periods of the ACD cycle. On a number of occasions, litter samples were obtained just prior to chick placement. Eimeria oocysts were isolated from all samples, counted by microscopy, and extracted for DNA to identify Eimeria species by ITS1 PCR. In general, Eimeria oocyst concentration in litter reached peak levels at 2-4 wk of grow-out regardless of coccidiosis control measure being used. However, peak oocyst numbers were sometimes delayed until 7-8 wk, indicating some level of Eimeria spp. drug resistance or incomplete vaccine coverage. Eimeria maxima , Eimeria acervulina , Eimeria praecox, and Eimeria tenella were generally present in all samples, and no difference in the species composition was noted between houses on a particular farm. While Eimeria species composition was similar among houses, Eimeria spp. oocyst levels exhibited sporadic peaks in one house of a given location's houses. Of particular interest was the observed correlation between E. maxima oocyst abundance and chick mortality. However, no correlation was observed in E. maxima oocyst levels, and the performance parameters adjusted feed conversion ratio and average daily weight gain. This study showed that understanding the dynamics of Eimeria spp. oocyst levels and species

  8. Optimization and application of fabric phase sorptive extraction coupled to ultra-high performance liquid chromatography tandem mass spectrometry for the determination of cytostatic drug residues in environmental waters.

    Science.gov (United States)

    Santana-Viera, Sergio; Guedes-Alonso, Rayco; Sosa-Ferrera, Zoraida; Santana-Rodríguez, José Juan; Kabir, Abuzar; Furton, Kenneth G

    2017-12-22

    Every year, hundreds of tons of organic pollutants reach the environment through effluents released from wastewater treatment plants worldwide, and many of these compounds have harmful effects on the aquatic ecosystem. A new class of emerging pollutants of high concern is cytostatic drugs, which are designed to treat different types of cancers by attacking cells. Environmental concentrations of cytostatic drugs are known to be in the range of ngL -1 , and for this reason, it is imperative to develop analytical methods of extraction and preconcentration to allow for subsequent instrumental analysis of these drugs. In this work, a rapid, simple and green method for the analysis of seven cytostatic drug compounds that are commonly used in anti-cancer therapies was developed using a novel extraction process based on a powerful miniaturized technique, fabric phase sorptive extraction (FPSE) coupled to ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). The major parameters that affect the extraction process were optimized. The new method shows good linearity, with a relative standard deviation (RSD) of less than 12%. Relative recoveries higher than 40% were obtained for the studied compounds, and the detection limit of the method was within the values at which these compounds are usually found in environmental water (0.20ngL -1 to 80ngL -1 ). The Limit of Quantification ranged from 0.68 to 267ngL -1 . Significant suppression of the signal due to the matrix effect, a common shortcoming attributed to interference from the extraction process as well as the use of ionization mode, was not observed. Subsequently, the method was applied to real wastewater samples from an effluent obtained from a hospital area and three wastewater treatment plants located in Gran Canaria Island, Spain. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. 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

  10. Cytogenetic and oxidative status of human lymphocytes after exposure to clinically relevant concentrations of antimalarial drugs atovaquone and proguanil hydrochloride in vitro.

    Science.gov (United States)

    Dinter, Domagoj; Gajski, Goran; Domijan, Ana-Marija; Garaj-Vrhovac, Vera

    2015-12-01

    Atovaquone (ATO) and proguanil hydrochloride (PROG) is the fixed combination for the prevention and treatment of Plasmodium falciparum malaria. As safe and effective antimalarial drugs are needed in both the treatment and the prophylaxis of malaria, this study was performed to investigate their possible cyto/genotoxic potential towards human lymphocytes and the possible mechanism responsible for it. Two different concentrations of ATO and PROG were used with and without S9 metabolic activation. The concentrations used were those found in human plasma when a fixed-dose combination of ATO and PROG was used: 2950/130 ng/mL after prophylactic treatment and 11 800/520 ng/mL after treatment of malaria, respectively. Possible cellular and DNA-damaging effects were evaluated by cell viability and alkaline comet assays, while oxidative stress potential was evaluated by formamidopyrimidine-DNA glycosylase (Fpg)-modified comet assay, in addition to measuring malondialdehyde and glutathione levels. According to our results, the ATO/PROG combination displayed only weak cyto/genotoxic potential towards human lymphocytes with no impact on oxidative stress parameters, suggesting that oxidative stress is not implicated in their mechanism of action towards human lymphocytes. Given that the key portion of the damaging effects was induced after S9 metabolic activation, it is to presume that the principal metabolite of PROG, cycloguanil, had the greatest impact. The obtained results indicate that the ATO/PROG combination is relatively safe for the consumption from the aspect of cyto/genotoxicity, especially if used for prophylactic treatment. Nevertheless, further cytogenetic research and regular patient monitoring are needed to minimize the risk of adverse events especially among frequent travellers. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  11. Albendazole residues in goat's milk: Interferences in microbial inhibitor tests used to detect antibiotics in milk

    OpenAIRE

    Romero, Tamara; Althaus, Rafael; Moya, Vicente Javier; Beltrán, María del Carmen; Reybroeck, Wim; Molina, María Pilar

    2016-01-01

    Albendazole (ABZ) residues in goat's milk and their effect on the response of microbial inhibitor tests used for screening antibiotics were evaluated. A total of 18 Murciano-Granadina goats were treated with ABZ and individually milked once a day over a 7-day period. ABZ quantification was performed by high performance liquid chromatography. The ABZ parent drug was not detected. The maximum concentration of its metabolites (ABZ sulfoxide, ABZ sulfone, and ABZ 2-aminosulfone) was reached on th...

  12. Determination of florfenicol residues in broiler meat and liver samples using RP-HPLC with UV-visible detection.

    Science.gov (United States)

    Nasim, Asma; Aslam, Bilal; Javed, Ijaz; Ali, Asghar; Muhammad, Faqir; Raza, Ahmad; Sindhu, Zia-ud-Din

    2016-03-15

    Broilers are vulnerable to various types of microorganisms, including Salmonella, Escherichia coli and Staphylococcus aureus, resulting in multiple infections. Broad-spectrum antibacterial drugs such as florfenicol (FF) are widely used in the treatment of such infections. Suspected residues of these drugs in body tissues of treated birds can be passed to humans through meat consumption and thus lead to serious ill effects on human health. The present study was designed to estimate the presence of FF residues in broiler meat and liver samples. The mean residual concentrations of FF in broiler meat and liver samples were 311.42 ± 186.56 and 2585.44 ± 1759.71 µg kg(-1) respectively, which are higher than their respective maximum residual limits (MRLs). The results showed that 126 and 24 samples were FF-positive and FF-negative respectively. Of the positive samples, 84 and 42 samples were above and below the MRL respectively. The results indicate the presence of FF residues in broiler meat and liver samples. Usage of this contaminated meat causes resistance in consumers and poses a public health threat. Thus there is a need to educate farmers about the ill effects of residual drugs on human health and their withdrawal times in poultry. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  13. The balance of flexibility and rigidity in the active site residues of hen egg white lysozyme

    International Nuclear Information System (INIS)

    Qi Jian-Xun; Jiang Fan

    2011-01-01

    The crystallographic temperature factors (B factor) of individual atoms contain important information about the thermal motion of the atoms in a macromolecule. Previously the theory of flexibility of active site has been established based on the observation that the enzyme activity is sensitive to low concentration denaturing agents. It has been found that the loss of enzyme activity occurs well before the disruption of the three-dimensional structural scaffold of the enzyme. To test the theory of conformational flexibility of enzyme active site, crystal structures were perturbed by soaking in low concentration guanidine hydrochloride solutions. It was found that many lysozyme crystals tested could still diffract until the concentration of guanidine hydrochloride reached 3 M. It was also found that the B factors averaged over individually collected data sets were more accurate. Thus it suggested that accurate measurement of crystal temperature factors could be achieved for medium-high or even medium resolution crystals by averaging over multiple data sets. Furthermore, we found that the correctly predicted active sites included not only the more flexible residues, but also some more rigid residues. Both the flexible and the rigid residues in the active site played an important role in forming the active site residue network, covering the majority of the substrate binding residues. Therefore, this experimental prediction method may be useful for characterizing the binding site and the function of a protein, such as drug targeting. (interdisciplinary physics and related areas of science and technology)

  14. Bioaccumulation and distribution of organochlorine residues across ...

    African Journals Online (AJOL)

    The transfer of organochlorine residues in the food chain and its distribution in the trophic levels was influenced by habitat, environmental conditions, feeding habit and biochemical composition of individual populations. The total residual concentration of OCPs in shellfish and fish ranged between 0.16 ppm and 0.69 ppm.

  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

    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

  16. 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

  17. Estimation of drug abuse in 9 Polish cities by wastewater analysis.

    Science.gov (United States)

    Klupczynska, Agnieszka; Dereziński, Paweł; Krysztofiak, Janusz; Kokot, Zenon J

    2016-03-01

    The aim of this work was to measure illicit drug residues in raw sewage samples collected from nine Polish cities in order to determine trends in illicit drug use in these urban populations. This is the first study involving an analysis of samples from several sewage treatment plants in Poland and covering such a large population. Concentration of illicit drugs was determined using a high performance liquid chromatography-tandem mass spectrometry method. The samples were subjected to a multistep preparation procedure with a solid phase extraction as a main pre-treatment step. Among the selected drugs investigated in the study, amphetamine was found in the greatest amounts in all sewage samples and consequently was the most prevalent drug of abuse. Higher loads of illicit drug residues were found during weekends compared to the weekdays, especially for 3,4-methylenedioxymethamphetamine (ecstasy) and benzoylecgonine, main metabolite of cocaine. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  18. Development of a Predictive Model for the Stabilizer Concentration Estimation in Microreservoir Transdermal Drug Delivery Systems Using Lipophilic Pressure-Sensitive Adhesives as Matrix/Carrier.

    Science.gov (United States)

    Chenevas-Paule, Clémence; Wolff, Hans-Michael; Ashton, Mark; Schubert, Martin; Dodou, Kalliopi

    2017-05-01

    Microreservoir-type transdermal drug delivery systems (MTDDS) can prevent drug crystallization; however, no current predictive model considers the impact of drug load and hydration on their physical stability. We investigated MTDDS films containing polyvinylpyrrolidone (PVP) as polymeric drug stabilizer in lipophilic pressure-sensitive adhesive (silicone). Medicated and unmedicated silicone films with different molar N-vinylpyrrolidone:drug ratios were prepared and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, microscopy, dynamic vapor sorption (DVS), and stability testing for 4 months at different storage conditions. Homogeneously distributed drug-PVP associates were observed when nonaqueous emulsions, containing drug-PVP (inner phase) and silicone adhesive (outer phase), were dried to films. DVS data were essential to predict physical stability at different humidities. A predictive thermodynamic model was developed based on drug-polymer hydrogen-bonding interactions, using the Hoffman equation, to estimate the drug-PVP ratio needed to obtain stable MTDDS and to evaluate the impact of humidity on their physical stability. This new approach considers the impact of polymorphism on drug solubility by using easily accessible experimental data (T m and DVS) and avoids uncertainties associated with the solubility parameter approach. In conclusion, a good fit of predicted and experimental data was observed. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Report on the third research co-ordination meeting of the coordinated research project: 'The development of strategies for the effective monitoring of veterinary drug residues in livestock and livestock products in developing countries' (D3.20.22)

    International Nuclear Information System (INIS)

    2005-01-01

    The third RCM for the CRP on the development of strategies for the effective monitoring of veterinary drug residues in livestock and livestock products in developing countries was held in Natal, Brazil, from 11-15 April 2005. The meeting was attended by ten Research Contract Holders, a second representative of the research group of the host country, two Research Agreement Holders, two Technical Contract Holders and the Scientific Secretary. The work in the second phase of this CRP has built upon the progress reported from the first phase, resulting in good quality immunoassay reagents, confirmatory methods and a number of validated methods. It is recommended that all contracts (with one exception), including technical contracts, be renewed to facilitate the completion of the work plans agreed at the meeting. A protocol for the validation of immunoassays will be provided by a Research Agreement Holder. The protocol has already been successfully applied for validation of an RIA method in Brazil. It is recommended that this protocol be adopted by all participants in the project to harmonize the validation of immunoassay methods developed. Work on the development of the 125 I-radioimmunoassay for chloramphenicol has not been satisfactory. It is recommended that this work is transferred to the research group in Brazil. The meeting agreed that the FAO/IAEA Joint Division's INFOCRIS database and associated e-learning modules are a very useful resource for developing country scientists. It is recommended to proceed with the expansion of the database as planned. In addition, it was suggested that a database and bibliography of original literature on, for example, pharmacokinetic and metabolism studies on veterinary drugs and hormonal growth promoters should be included. Much of this data was published many years ago and is very difficult to access, but is of importance in the design and development of methods. Some of the results generated by CRP participants should be

  20. Effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs on the production of reactive oxygen species by activated rat neutrophils

    Directory of Open Access Journals (Sweden)

    Paino I.M.M.

    2005-01-01

    Full Text Available The release of reactive oxygen specie (ROS by activated neutrophil is involved in both the antimicrobial and deleterious effects in chronic inflammation. The objective of the present investigation was to determine the effect of therapeutic plasma concentrations of non-steroidal anti-inflammatory drugs (NSAIDs on the production of ROS by stimulated rat neutrophils. Diclofenac (3.6 µM, indomethacin (12 µM, naproxen (160 µM, piroxicam (13 µM, and tenoxicam (30 µM were incubated at 37ºC in PBS (10 mM, pH 7.4, for 30 min with rat neutrophils (1 x 10(6 cells/ml stimulated by phorbol-12-myristate-13-acetate (100 nM. The ROS production was measured by luminol and lucigenin-dependent chemiluminescence. Except for naproxen, NSAIDs reduced ROS production: 58 ± 2% diclofenac, 90 ± 2% indomethacin, 33 ± 3% piroxicam, and 45 ± 6% tenoxicam (N = 6. For the lucigenin assay, naproxen, piroxicam and tenoxicam were ineffective. For indomethacin the inhibition was 52 ± 5% and diclofenac showed amplification in the light emission of 181 ± 60% (N = 6. Using the myeloperoxidase (MPO/H2O2/luminol system, the effects of NSAIDs on MPO activity were also screened. We found that NSAIDs inhibited both the peroxidation and chlorinating activity of MPO as follows: diclofenac (36 ± 10, 45 ± 3%, indomethacin (97 ± 2, 100 ± 1%, naproxen (56 ± 8, 76 ± 3%, piroxicam (77 ± 5, 99 ± 1%, and tenoxicam (90 ± 2, 100 ± 1%, respectively (N = 3. These results show that therapeutic levels of NSAIDs are able to suppress the oxygen-dependent antimicrobial or oxidative functions of neutrophils by inhibiting the generation of hypochlorous acid.

  1. Microrganismos patogênicos, celularidade e resíduos de antimicrobianos no leite bovino produzido no sistema orgânico Pathogenic microorganisms, somatic cell count and drug residues evaluation in organic bovine milk

    Directory of Open Access Journals (Sweden)

    Márcio Garcia Ribeiro

    2009-01-01

    antimicrobianos em fazendas de leite orgânico.In last years increase the importance of milk quality and conditions of bovine milking. Simultaneously, increase the interest about organic milk and derivates. The aim of present study was investigate the milk pathogens, sensitivity and multiple drug resistance of isolates, somatic cell count and residues of drugs in milk, from cattle with and without mastitis, come from four little organic dairy farms in State of São Paulo, Brazil. Were used 148 cattle on the middle period of lactation. From these, two showed clinical mastitis, 72 subclinical mastitis and 74 without signs of mammary inflammation (controls. Staphylococcusaureus (25.7%, Streptococcus spp. (21.4%, Corynebacterium bovis (12.9%, Streptococcus agalactiae (4.3% and Staphylococcus spp. (4.3% were the more-frequent microorganisms isolated from animals with mastitis. Aspergillus spp. was isolated from one animal. Ceftiofur (95.2%, oxacillin (84.2%, gentamicin (76.3% and cefoperazone (70.3% were the more effective drugs. High resistance of isolates were found to penicillin (53.5%, ampicillin (41.6% and neomycin (38.6%. Multiple drug resistance to three or more drugs was observed in 40 (39.6% isolates. Media of somatic cell count encountered in animals with mastitis and controls were 175,742.67cs/mL and 58,227.6 cs/mL, respectively. Antimicrobials residues in milk were detected in four (2.7% animals. The present findings showed the low somatic cell count of animals, indicative of good quality of milk. However, pointed the need of control measures for contagious pathogens of bovine mastitis and more attention for prohibition of antimicrobial use in organic dairy farms.

  2. Actinide recovery from pyrochemical residues

    International Nuclear Information System (INIS)

    Avens, L.R.; Clifton, D.G.; Vigil, A.R.

    1984-01-01

    A new process for recovery of plutonium and americium from pyrochemical waste has been demonstrated. It is based on chloride solution anion exchange at low acidity, which eliminates corrosive HCl fumes. Developmental experiments of the process flowsheet concentrated on molten salt extraction (MSE) residues and gave >95% plutonium and >90% americium recovery. The recovered plutonium contained 6 = from high chloride-low acid solution. Americium and other metals are washed from the ion exchange column with 1N HNO 3 -4.8M NaCl. The plutonium is recovered, after elution, via hydroxide precipitation, while the americium is recovered via NaHCO 3 precipitation. All filtrates from the process are discardable as low-level contaminated waste. Production-scale experiments are now in progress for MSE residues. Flow sheets for actinide recovery from electrorefining and direct oxide reduction residues are presented and discussed

  3. Actinide recovery from pyrochemical residues

    International Nuclear Information System (INIS)

    Avens, L.R.; Clifton, D.G.; Vigil, A.R.

    1985-05-01

    We demonstrated a new process for recovering plutonium and americium from pyrochemical waste. The method is based on chloride solution anion exchange at low acidity, or acidity that eliminates corrosive HCl fumes. Developmental experiments of the process flow chart concentrated on molten salt extraction (MSE) residues and gave >95% plutonium and >90% americium recovery. The recovered plutonium contained 6 2- from high-chloride low-acid solution. Americium and other metals are washed from the ion exchange column with lN HNO 3 -4.8M NaCl. After elution, plutonium is recovered by hydroxide precipitation, and americium is recovered by NaHCO 3 precipitation. All filtrates from the process can be discardable as low-level contaminated waste. Production-scale experiments are in progress for MSE residues. Flow charts for actinide recovery from electro-refining and direct oxide reduction residues are presented and discussed

  4. Determination of oxytetracycline residues in cattle meat marketed in the Kilosa district, Tanzania

    Directory of Open Access Journals (Sweden)

    Zuhura I. Kimera

    2015-11-01

    Full Text Available Oxytetracycline is used to treat various diseases in cattle. However, its use may be associated with unacceptable residue levels in food. Oxytetracycline residues in tissues from indigenous cattle were determined in a cross-sectional study conducted in the Kilosa district, Tanzania, between November 2012 and April 2013. A total of 60 tissue samples, including muscle, liver and kidney, were collected from slaughterhouses and butchers and analysed for oxytetracycline using high-performance liquid chromatography. Oxytetracycline residues were found in 71.1% of the samples, of which 68.3% were above acceptable regulatory levels. The mean concentration of oxytetracycline across tissues was 3401.1 μg/kg ± 879.3 μg/kg; concentrations in muscle, liver and kidney were 2604.1 μg/kg ± 703.7 μg/kg, 3434.4 μg/kg ± 606.4 μg/kg and 3533.1 μg/kg ± 803.6 μg/kg, respectively. High levels of oxytetracycline residue in meat from indigenous cattle may pose a health threat to consumers in Kilosa. The findings possibly reflect a general lack of implementation of recommended withdrawal periods, ignorance about drug use and lack of extension services. Strict regulation of the use of antimicrobial drugs in the livestock industry and associated testing of animal-derived food sources prior to marketing are required.

  5. Detection of antibiotic residues in poultry meat.

    Science.gov (United States)

    Sajid, Abdul; Kashif, Natasha; Kifayat, Nasira; Ahmad, Shabeer

    2016-09-01

    The antibiotic residues in poultry meat can pose certain hazards to human health among them are sensitivity to antibiotics, allergic reactions, mutation in cells, imbalance of intestinal micro biota and bacterial resistance to antibiotics. The purpose of the present paper was to detect antibiotic residue in poultry meat. During the present study a total of 80 poultry kidney and liver samples were collected and tested for detection of different antibiotic residues at different pH levels Eschericha coli at pH 6, 7 and Staphyloccocus aureus at pH 8 & 9. Out of 80 samples only 4 samples were positive for antibiotic residues. The highest concentrations of antibiotic residue found in these tissues were tetracycline (8%) followed by ampicilin (4%), streptomycine (2%) and aminoglycosides (1%) as compared to other antibiotics like sulfonamides, neomycine and gentamycine. It was concluded that these microorganism at these pH levels could be effectively used for detection of antibiotic residues in poultry meat.

  6. A review on the relation between the brain-serum concentration ratio of drugs and the influence of P-glycoprotein

    DEFF Research Database (Denmark)

    Ejsing, Thomas Broeng; Morling, Niels; Linnet, Kristian

    2007-01-01

    This overview on the brain-serum relationship for drugs illustrates the importance of the drug transporter P-glycoprotein at the blood-brain barrier. Generally, an inverse relationship exists between the magnitude of the brain-serum ratio and the influence of P-glycoprotein. Concerning...

  7. Acute and residual interactive effects of repeated administrations of oral methamphetamine and alcohol in humans

    Science.gov (United States)

    Kirkpatrick, Matthew G.; Gunderson, Erik W.; Levin, Frances R.; Foltin, Richard W.; Hart, Carl L.

    2011-01-01

    Although methamphetamine and alcohol are commonly used together in a binge-like pattern, there is a dearth of empirical data investigating the repeated effects of this drug combination. The current study examined acute and residual mood, performance, and physiological effects of methamphetamine alone, alcohol alone, and the combination. Nine adult male volunteers completed this 20-day within-participant, residential laboratory study. During four 5-day blocks of sessions, participants were administered oral methamphetamine (0, 10 mg) combined with alcohol (0, 0.375, 0.75 g/kg) three times (day 2: AM, day 2: PM, and day 3: PM). Breath alcohol concentrations, cardiovascular, subjective, and cognitive/psychomotor performance effects were assessed before drug administration and repeatedly thereafter. Subjective and objective sleep measures were also assessed; residual effects were assessed on days 3–5 of each block. Following the first drug administration, the methamphetamine–alcohol combination produced greater elevations of heart rate and ratings of “good drug effect” compared to either drug alone. Methamphetamine attenuated alcohol-related performance decrements and feelings of intoxication, whereas alcohol attenuated methamphetamine-related sleep disruptions. By the third administration, many of these effects were significantly diminished, suggesting that participants developed tolerance. Few residual effects were observed. These data show that methamphetamine combined with alcohol produced a profile of effects that was different from the effects of either drug alone. The largely positive effects of the drug combination (i.e., greater euphoria, and fewer performance and sleep disruptions) might explain why these drugs are often used in combination. PMID:21748253

  8. Psychoactive pharmaceutical residues in the watersheds of Galicia (Spain).

    Science.gov (United States)

    Esteban, Sara; Valcárcel, Yolanda; Catalá, Myriam; Castromil, Miguel González

    2012-01-01

    To monitor the presence of pharmaceutical residues of 14 psychoactive drugs belonging to three therapeutic groups in the watersheds of Galicia (Spain). Five sewage treatment plants were selected in the main cities of Galicia. Thirteen psychoactive pharmaceutical compounds and one metabolite were chosen. In addition, tap water samples were taken from public places and private residences in the selected cities. In all the water samples analyzed, the highest concentrations corresponded to the group of anxiolytics. In particular, high concentrations of lorazepam were found in river and tap water samples. This investigation demonstrates the presence of psychoactive pharmaceuticals in the watersheds of the autonomous region of Galicia and the conversion of metabolites to parent compounds. This work also shows the need to increase environmental monitoring of watersheds and to improve sewage and drinking water treatment processes to remove these pharmaceuticals. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

  9. 9 CFR 318.20 - Use of animal drugs.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Use of animal drugs. 318.20 Section... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products if such residues are from drugs which have been approved by the Food and Drug Administration and any such...

  10. Ammoniated maize residue for the fattening of lambs | Seed | South ...

    African Journals Online (AJOL)

    The use of ammoniated maize residue as a replacement for maize meal in the diet for fattening lambs, was investigated. Ammoniation of maize residue increased average daily DMI and ADG at the 0 and 20oh concentrate levels. The feed conversions to carcass in lambs fed untreated maize residue with 40,60 or 80% ...

  11. Ingestion of Milk Containing Very Low Concentration of Antimicrobials: Longitudinal Effect on Fecal Microbiota Composition in Preweaned Calves.

    Directory of Open Access Journals (Sweden)

    Richard Van Vleck Pereira

    Full Text Available Although antimicrobial drugs are central to combat disease in modern medicine, the use of these drugs can have undesired consequences for human and animal health. One consequence is the post-therapy excretion of pharmacological agents, such as the elimination of drug residues at very low concentrations in the milk of lactating mammals. Limited information is currently available on the impact from the exposure of the gut microbiota to drug residues using in vivo natural models. The objective of our study was to address this knowledge gap and evaluate the effect on the fecal microbiota composition from feeding preweaned dairy calves raw milk with residual concentrations of ampicillin, ceftiofur, penicillin, and oxytetracycline from birth to weaning. At birth, thirty calves were randomly assigned to a controlled feeding trial where: 15 calves were fed raw milk with no drug residues (NR, and 15 calves were fed raw milk with drug residues (DR by adding ceftiofur, penicillin, ampicillin, and oxytetracycline at final concentrations in the milk of 0.1, 0.005, 0.01, and 0.3 μg/ml, respectively. Fecal samples were rectally collected from each calf once a week starting at birth, prior to the first feeding in the trial (pre-treatment, until 6 weeks of age. Sequencing of the microbial 16S rRNA genes was conducted using the Illumina MiSeq, which provides a high resolution of the microbiota down to the genus level. Discriminant analysis showed that, except for pre-treatment samples, calves fed milk with drug residues and calves fed milk without drug residues easily discriminated at the genus level on their weekly microbial profile. However, analysis comparing the abundance of taxon between NR and DR showed significant differences only at the genus levels, and not at the phylum, class, order or family levels. These results suggest that although drug residues can result in clear discriminate gut microbial communities, they do not result in disruption of

  12. Nicarbazin contamination in feeds as a cause of residues in eggs.

    Science.gov (United States)

    Cannavan, A; Ball, G; Kennedy, D G

    2000-10-01

    A survey was carried out to investigate the prevalence of nicarbazin residues in eggs in Northern Ireland. Nicarbazin, in the form of 4,4'-dinitrocarbanilide (DNC), was detected in 39 of the 190 eggs analysed. An experiment was designed to establish the relationship between nicarbazin-contaminated feed and nicarbazin residues in eggs. The concentrations of both the DNC and 4,6-dimethyl-2-hydroxypyrimidine (DHP) components of the drug in eggs were proportional to feed levels. The maximum feed nicarbazin concentration of 12.1 mg/kg (8.6 mg/kg DNC and 3.5 mg/kg DHP) gave rise to mean maximum whole egg concentrations of 631 micrograms/kg DNC and 51.8 micrograms/kg DHP. After withdrawal of the experimental diet, DNC was undetectable in eggs after 12 days and DHP after 3 days. Feed contaminated with nicarbazin at concentrations greater than about 2 mg/kg gave rise to egg DNC residues at concentrations greater than the Differential Action Limit (DAL) set by the UK (100 micrograms/kg). DNC was contained almost entirely in the yolk of the egg, whereas DHP was distributed between albumen and yolk in a ratio of approximately 3:1.

  13. Isotopic tracer aided studies of fenvalerate residues in stored rice

    International Nuclear Information System (INIS)

    Varca, L.M.; Sanchez, T.E.; Magallona, E.D.

    1990-01-01

    Following application of 14 C-fenvalerate to milled rice and paddy rice at a concentration of 0.33 mg/kg, only insignificant losses were measured after 9 months. Distribution patterns in surface, methanol extractable and bound residues were studied. Paddy rice contained less extractable residues than milled rice, with the major part being found in the husk. Bound residues in both milled and paddy rice decreased also with length of storage; as much as 30% was found as bound residues after nine months. Cooking reduced the insecticide residues in milled rice by 33-40% and residues in paddy rice by 58%. (author). 8 refs, 1 fig., 4 tabs

  14. Effects of various antipsychotic drugs upon the striatal concentrations of para-hydroxyphenylacetic acid and meta-hydroxyphenylacetic acid in the mouse.

    OpenAIRE

    Juorio, A. V.; McQuade, P. S.

    1983-01-01

    The endogenous concentrations of p- and m-hydroxyphenylacetic acid in the mouse caudate nucleus were determined by a gas chromatographic or a gas chromatographic-mass spectrometric technique and the concentrations were about 30 and 11 ng g-1 respectively. The subcutaneous administration of (+)-butaclamol (1 mg kg-1), haloperidol (5 mg kg-1), molindone (100 mg kg-1), sulpiride (50 mg kg-1) or chlorpromazine (20 mg kg-1) increased the concentration of mouse striatal p- and m-hydroxyphenylacetic...

  15. Pharmacokinetics and egg residues after oral administration of a single dose of meloxicam in domestic chickens (Gallus domesticus).

    Science.gov (United States)

    Souza, Marcy J; Bergman, Joan B; White, Molly S; Gordon, Kristen I; Gerhardt, Lillian E; Cox, Sherry K

    2017-08-01

    OBJECTIVE To determine the pharmacokinetics of meloxicam in domestic hens and duration and quantity of drug residues in their eggs following PO administration of a single dose (1 mg of meloxicam/kg). ANIMALS 8 healthy adult White Leghorn hens. PROCEDURES Hens were administered 1 mg of meloxicam/kg PO once. A blood sample was collected immediately before and at intervals up to 48 hours after drug administration. The hens' eggs were collected for 3 weeks after drug administration. Samples of the hens' plasma, egg whites (albumen), and egg yolks were analyzed by high-performance liquid chromatography. RESULTS The half-life, maximum concentration, and time to maximum concentration of meloxicam in plasma samples were 2.8 hours, 7.21 μg/mL, and 2 hours, respectively. Following meloxicam administration, the drug was not detected after 4 days in egg whites and after 8 days in egg yolks. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that meloxicam administered at a dose of 1 mg/kg PO in chickens appears to maintain plasma concentrations equivalent to those reported to be therapeutic for humans for 12 hours. The egg residue data may be used to aid establishment of appropriate drug withdrawal time recommendations.

  16. Population pharmacokinetics/pharmacodynamics of erlotinib and pharmacogenomic analysis of plasma and cerebrospinal fluid drug concentrations in Japanese patients with non-small cell lung cancer.

    Science.gov (United States)

    Fukudo, Masahide; Ikemi, Yasuaki; Togashi, Yosuke; Masago, Katsuhiro; Kim, Young Hak; Mio, Tadashi; Terada, Tomohiro; Teramukai, Satoshi; Mishima, Michiaki; Inui, Ken-Ichi; Katsura, Toshiya

    2013-07-01

    Erlotinib shows large inter-patient pharmacokinetic variability, but the impact of early drug exposure and genetic variations on the clinical outcomes of erlotinib remains fully investigated. The primary objective of this study was to clarify the population pharmacokinetics/pharmacodynamics of erlotinib in Japanese patients with non-small cell lung cancer (NSCLC). The secondary objective was to identify genetic determinant(s) for the cerebrospinal fluid (CSF) permeability of erlotinib and its active metabolite OSI-420. A total of 88 patients treated with erlotinib (150 mg/day) were enrolled, and CSF samples were available from 23 of these patients with leptomeningeal metastases. Plasma and CSF concentrations of erlotinib and OSI-420 were measured by high-performance liquid chromatography with UV detection. Population pharmacokinetic analysis was performed with the nonlinear mixed-effects modelling program NONMEM. Germline mutations including ABCB1 (1236C>T, 2677G>T/A, 3435C>T), ABCG2 (421C>A), and CYP3A5 (6986A>G) polymorphisms, as well as somatic EGFR activating mutations if available, were examined. Early exposure to erlotinib and its safety/efficacy relationship were evaluated. The apparent clearance of erlotinib and OSI-420 were significantly decreased by 24 and 35 % in patients with the ABCG2 421A allele, respectively (p OSI-420 (p model showed that erlotinib trough (C0) levels on day 8 were an independent risk factor for the development of grade ≥2 diarrhea (p = 0.037) and skin rash (p = 0.031). Interstitial lung disease (ILD)-like events occurred in 3 patients (3.4 %), and the median value of erlotinib C0 levels adjacent to these events was approximately 3 times higher than that in patients who did not develop ILD (3253 versus 1107 ng/mL; p = 0.014). The objective response rate in the EGFR wild-type group was marginally higher in patients achieving higher erlotinib C0 levels (≥1711 ng/mL) than that in patients having lower erlotinib C0

  17. A Simple Surface-Enhanced Raman Spectroscopic Method for on-Site Screening of Tetracycline Residue in Whole Milk

    Directory of Open Access Journals (Sweden)

    Sagar Dhakal

    2018-02-01

    Full Text Available Therapeutic and subtherapeutic use of veterinary drugs has increased the risk of residue contamination in animal food products. Antibiotics such as tetracycline are used for mastitis treatment of lactating cows. Milk expressed from treated cows before the withdrawal period has elapsed may contain tetracycline residue. This study developed a simple surface-enhanced Raman spectroscopic (SERS method for on-site screening of tetracycline residue in milk and water. Six batches of silver colloid nanoparticles were prepared for surface enhancement measurement. Milk-tetracycline and water-tetracycline solutions were prepared at seven concentration levels (1000, 500, 100, 10, 1, 0.1, and 0.01 ppm and spiked with silver colloid nanoparticles. A 785 nm Raman spectroscopic system was used for spectral measurement. Tetracycline vibrational modes were observed at 1285, 1317 and 1632 cm−1 in water-tetracycline solutions and 1322 and 1621 cm−1 (shifted from 1317 and 1632 cm−1, respectively in milk-tetracycline solutions. Tetracycline residue concentration as low as 0.01 ppm was detected in both the solutions. The peak intensities at 1285 and 1322 cm−1 were used to estimate the tetracycline concentrations in water and milk with correlation coefficients of 0.92 for water and 0.88 for milk. Results indicate that this SERS method is a potential tool that can be used on-site at field production for qualitative and quantitative detection of tetracycline residues.

  18. Reduction and Scavenging of Chemically Reactive Drug Metabolites by NAD(P)H:Quinone Oxidoreductase 1 and NRH:Quinone Oxidoreductase 2 and Variability in Hepatic Concentrations

    NARCIS (Netherlands)

    den Braver-Sewradj, Shalenie P; den Braver, Michiel W; Toorneman, Robin M; van Leeuwen, Stephanie; Zhang, Yongjie; Dekker, Stefan J; Vermeulen, Nico P E; Commandeur, Jan N M; Vos, J Chris

    2018-01-01

    Detoxicating enzymes NAD(P)H:quinone oxidoreductase 1 (NQO1) and NRH:quinone oxidoreductase 2 (NQO2) catalyze the two-electron reduction of quinone-like compounds. The protective role of the polymorphic NQO1 and NQO2 enzymes is especially of interest in the liver as the major site of drug

  19. Residues of tritium-labeled morantel in lactating dairy cattle

    International Nuclear Information System (INIS)

    Lynch, M.J.; Mosher, F.R.; Burnett, D.M.; Newby, T.J.

    1987-01-01

    Residues of morantel and its metabolites were monitored in plasma, urine, and milk of five lactating dairy cattle that received an oral dose of [4,4-pyrimidyl- 3 H 2 ]morantel tartrate at 10 mg/kg. Drug-related radioactivity peaked in plasma at 8 h and in milk by the second milking, postdose, and was 170 and 84 ng/mL, respectively. The fraction of total residues in milk convertible to the marker compound, N-methyl-1,3-propanediamine, was 0.38 on the basis of a comparison of the areas under the curves for total and marker residues. Five days after dosing, 3.9% of the total radioactivity in liver was recovered as tritium water. Total drug-related residues in this target tissue averaged 1.15 μg/g. About half of the drug-related residues in liver was unextractable and was classified by bound

  20. Residual gas analysis

    International Nuclear Information System (INIS)

    Berecz, I.

    1982-01-01

    Determination of the residual gas composition in vacuum systems by a special mass spectrometric method was presented. The quadrupole mass spectrometer (QMS) and its application in thin film technology was discussed. Results, partial pressure versus time curves as well as the line spectra of the residual gases in case of the vaporization of a Ti-Pd-Au alloy were demonstrated together with the possible construction schemes of QMS residual gas analysers. (Sz.J.)

  1. Disposal of radioactive residuals requires careful planning

    International Nuclear Information System (INIS)

    Pontius, F.W.

    1994-01-01

    Radionuclides removed from source waters during water treatment become concentrated in residual liquids and sludges. Treatment technologies used to remove these contaminants from source waters may generate wastes that contain substantial radioactivity. Water systems that install one or more of these technologies in order to comply with the maximum contaminant levels (MCLs) eventually adopted must dispose of the residuals. Disposal of radionuclide-containing wastes can be especially difficult, depending on the nature and amount of radioactivity present

  2. Ammoniated maJze residue for the fattening of lambs

    African Journals Online (AJOL)

    of feed cost per kg carcass gain, a balanced diet containing untreated maize residue and 67,6t/a concentrate could be replaced by a balanced diet containing ammoniated maize residue and no energy concentrate. The increased dressing percentage and reduced ruminal digesta mass, pH and water volume owing to ...

  3. 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

  4. Natural radioactivity in petroleum residues

    International Nuclear Information System (INIS)

    Gazineu, M.H.P.; Gazineu, M.H.P.; Hazin, C.A.; Hazin, C.A.

    2006-01-01

    The oil extraction and production industry generates several types of solid and liquid wastes. Scales, sludge and water are typical residues that can be found in such facilities and that can be contaminated with Naturally Occurring Radioactive Material (N.O.R.M.). As a result of oil processing, the natural radionuclides can be concentrated in such residues, forming the so called Technologically Enhanced Naturally Occurring Radioactive Material, or T.E.N.O.R.M.. Most of the radionuclides that appear in oil and gas streams belong to the 238 U and 232 Th natural series, besides 40 K. The present work was developed to determine the radionuclide content of scales and sludge generated during oil extraction and production operations. Emphasis was given to the quantification of 226 Ra, 228 Ra and 40 K since these radionuclides,are responsible for most of the external exposure in such facilities. Samples were taken from the P.E.T.R.O.B.R.A.S. unity in the State of Sergipe, in Northeastern Brazil. They were collected directly from the inner surface of water pipes and storage tanks, or from barrels stored in the waste storage area of the E and P unit. The activity concentrations for 226 Ra, 228 Ra and 40 K were determined by using an HP Ge gamma spectrometric system. The results showed concentrations ranging from 42.7 to 2,110.0 kBq/kg for 226 Ra, 40.5 to 1,550.0 kBq/kg for 228 Ra, and 20.6 to 186.6 kBq/kg for 40 K. The results highlight the importance of determining the activity concentration of those radionuclides in oil residues before deciding whether they should be stored or discarded to the environment. (authors)

  5. Natural radioactivity in petroleum residues

    Energy Technology Data Exchange (ETDEWEB)

    Gazineu, M.H.P. [UNICAP, Dept. de Quimica, Recife (Brazil); Gazineu, M.H.P.; Hazin, C.A. [UFPE, Dept. de Energia Nuclear, Recife (Brazil); Hazin, C.A. [Centro Regional de Ciencias Nucleares/ CNEN, Recife (Brazil)

    2006-07-01

    The oil extraction and production industry generates several types of solid and liquid wastes. Scales, sludge and water are typical residues that can be found in such facilities and that can be contaminated with Naturally Occurring Radioactive Material (N.O.R.M.). As a result of oil processing, the natural radionuclides can be concentrated in such residues, forming the so called Technologically Enhanced Naturally Occurring Radioactive Material, or T.E.N.O.R.M.. Most of the radionuclides that appear in oil and gas streams belong to the {sup 238}U and {sup 232}Th natural series, besides 40 K. The present work was developed to determine the radionuclide content of scales and sludge generated during oil extraction and production operations. Emphasis was given to the quantification of {sup 226}Ra, {sup 228}Ra and 40 K since these radionuclides,are responsible for most of the external exposure in such facilities. Samples were taken from the P.E.T.R.O.B.R.A.S. unity in the State of Sergipe, in Northeastern Brazil. They were collected directly from the inner surface of water pipes and storage tanks, or from barrels stored in the waste storage area of the E and P unit. The activity concentrations for {sup 226}Ra, {sup 228}Ra and 40 K were determined by using an HP Ge gamma spectrometric system. The results showed concentrations ranging from 42.7 to 2,110.0 kBq/kg for {sup 226}Ra, 40.5 to 1,550.0 kBq/kg for {sup 228}Ra, and 20.6 to 186.6 kBq/kg for 40 K. The results highlight the importance of determining the activity concentration of those radionuclides in oil residues before deciding whether they should be stored or discarded to the environment. (authors)

  6. An integrated approach to care attracts people living with HIV who use illicit drugs in an urban centre with a concentrated HIV epidemic

    Directory of Open Access Journals (Sweden)

    S. Fernando

    2016-11-01

    Full Text Available Abstract Background People living with HIV (PLHIV who are also marginalized by social and structural inequities often face barriers to accessing and adhering to HIV treatment and care. The Dr. Peter Centre (DPC is a non-profit integrated care facility with a supervised injection room that serves PLHIV experiencing multiple barriers to social and health services in Vancouver, Canada. This study examines whether the DPC is successful in drawing in PLHIV with complex health issues, including addiction. Methods Using data collected by the Longitudinal Investigations into Supportive and Ancillary health services (LISA study from July 2007 to January 2010, linked with clinical variables available through the British Columbia Centre for Excellence in HIV/AIDS Drug Treatment Program, we identified DPC and non-DPC clients with a history of injection drug use. Bivariable and multivariable logistic regression analyses compared socio-demographic and clinical characteristics of DPC clients (n = 76 and non-DPC clients (n = 482 with a history of injection drug use. Results Of the 917 LISA participants included within this analysis, 100 (10.9% reported being a DPC client, of which 76 reported a history of injection drug use. Adjusted results found that compared to non-DPC clients with a history of injection drug use, DPC-clients were more likely to be male (AOR: 4.18, 95% CI = 2.09–8.37; use supportive services daily vs. less than daily (AOR: 3.16, 95% CI = 1.79–5.61; to have been diagnosed with a mental health disorder (AOR: 2.11; 95% CI: 1.12–3.99; to have a history of interpersonal violence (AOR: 2.76; 95% CI: 1.23–6.19; and to have ever experienced ART interruption longer than 1 year (AOR: 2.39; 95% CI: 1.38–4.15. Conclusions Our analyses suggest that the DPC operating care model engages PLHIV with complex care needs, highlighting that integrated care facilities are needed to support the multiple intersecting vulnerabilities faced

  7. Desenvolvimento e validação do método QuEChERS na determinação de resíduos de medicamentos veterinários em leite e carne de búfalo Development and validation of the QuEChERS method for the determination of veterinary drug residues in buffalo milk and meat

    Directory of Open Access Journals (Sweden)

    Silvia H. G. Brondi

    2013-01-01

    Full Text Available Analytical methods were developed and validated to determine residues of veterinary drugs in buffalo milk and meat, using the QuEChERS method and gas chromatography-mass spectrometry. Both milk and meat, at 2 g of sample, 4 mL of acetonitrile, 0.8 g of MgSO4 and 0.2 g of NaCl, were used in the liquid-liquid partition, whereas 50 mg of C18, 50 mg of PSA and 150 mg of MgSO4 were employed in the dispersive solid-phase extraction (d-SPE. The methods showed sensitivity, precision and accuracy. The quantitation limits were in agreement with the maximum residue limit established by the Codex Alimentarius, FAO and WHO.

  8. A sample preparation process for LC-MS/MS analysis of total protein drug concentrations in monkey plasma samples with antibody.

    Science.gov (United States)

    Ji, Qin C; Rodila, Ramona; El-Shourbagy, Tawakol A

    2007-03-01

    The determination of protein concentrations in plasma samples often provides essential information in biomedical research, clinical diagnostics, and pharmaceutical discovery and development. Binding assays such as ELISA determine meaningful free analyte concentrations by using specific antigen or antibody reagents. Concurrently, mass spectrometric technology is becoming a promising complementary method to traditional binding assays. Mass spectrometric assays generally provide measurements of the total protein analyte concentration. However, it was found that antibodies may bind strongly with the protein analyte such that total concentrations cannot be determined. Thus, a sample preparation process was developed which included a novel "denaturing" step to dissociate binding between antibodies and the protein analyte prior to solid phase extraction of plasma samples and LC-MS/MS analysis. In so doing, the total protein analyte concentrations can be obtained. This sample preparation process was further studied by LC-MS analysis with a full mass range scan. It was found that the protein of interest and other plasma peptides were pre-concentrated, while plasma albumin was depleted in the extracts. This capability of the sample preparation process could provide additional advantages in proteomic research for biomarker discovery and validation. The performance of the assay with the novel denaturing step was further evaluated. The linear dynamic range was between 100.9ng/mL and 53920.0ng/mL with a coefficient of determination (r(2)) ranging from 0.9979 and 0.9997. For LLOQ and ULOQ samples, the inter-assay CV was 12.6% and 2.7% and inter-assay mean accuracies were 103.7% and 99.5% of theoretical concentrations, respectively. For QC samples, the inter-assay CV was between 2.1% and 4.9%, and inter-assay mean accuracies were between 104.1% and 110.0% of theoretical concentrations.

  9. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI.

    Science.gov (United States)

    Kegel, Victoria; Pfeiffer, Elisa; Burkhardt, Britta; Liu, Jia L; Zeilinger, Katrin; Nüssler, Andreas K; Seehofer, Daniel; Damm, Georg

    2015-01-01

    Drug induced liver injury (DILI) is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC) sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2 ± 0.9 × 10(6) cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay) and cell activity (XTT assay). The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  10. Subtoxic Concentrations of Hepatotoxic Drugs Lead to Kupffer Cell Activation in a Human In Vitro Liver Model: An Approach to Study DILI

    Directory of Open Access Journals (Sweden)

    Victoria Kegel

    2015-01-01

    Full Text Available Drug induced liver injury (DILI is an idiosyncratic adverse drug reaction leading to severe liver damage. Kupffer cells (KC sense hepatic tissue stress/damage and therefore could be a tool for the estimation of consequent effects associated with DILI. Aim of the present study was to establish a human in vitro liver model for the investigation of immune-mediated signaling in the pathogenesis of DILI. Hepatocytes and KC were isolated from human liver specimens. The isolated KC yield was 1.2±0.9×106 cells/g liver tissue with a purity of >80%. KC activation was investigated by the measurement of reactive oxygen intermediates (ROI, DCF assay and cell activity (XTT assay. The initial KC activation levels showed broad donor variability. Additional activation of KC using supernatants of hepatocytes treated with hepatotoxic drugs increased KC activity and led to donor-dependent changes in the formation of ROI compared to KC incubated with supernatants from untreated hepatocytes. Additionally, a compound- and donor-dependent increase in proinflammatory cytokines or in anti-inflammatory cytokines was detected. In conclusion, KC related immune signaling in hepatotoxicity was successfully determined in a newly established in vitro liver model. KC were able to detect hepatocyte stress/damage and to transmit a donor- and compound-dependent immune response via cytokine production.

  11. Drogas de abuso em águas naturais e residuárias urbanas: ocorrência, determinação e aplicações forenses Drugs of abuse in waters and wastewaters: occurrence, analytical determination and forensic applications

    Directory of Open Access Journals (Sweden)

    Rafael Silva Feitosa

    2013-01-01

    Full Text Available Drugs of abuse are commonly used outside medical or legal settings where their production, marketing and consumption are subject to legal summons and/or intervention. Classified as emerging contaminants, these substances have been recently detected in samples of environmental concern, such as waters and wastewaters. This review presents the state-of-the-art on the methodological approaches used in sample preparation, the main techniques applied in analytical determination at trace levels, as well as the use of information related to the drug or its metabolite concentration in sewage samples to empirically estimate the consumption of drugs of abuse in a city or region.

  12. Report on the first research co-ordination meeting of the co-ordinated research project: 'The development of strategies for the effective monitoring of veterinary drug residues in livestock and livestock products in developing countries' (D3.20.22)

    International Nuclear Information System (INIS)

    2002-01-01

    The first Research Co-ordination Meeting (RCM) of the Co-ordinated Research Project (CRP) on 'the development of strategies for the effective monitoring of veterinary drug residues in livestock and livestock products in developing countries' was held in the Vienna International Centre from 2 to 6 September 2002. Twelve Research Contracts (RCs) and 3 Research Agreements (RAs) have been awarded under this CRP and all awardees, the Project Officer and a guest speaker from the Austrian Agency for Health and Food Safety (AAHFS) participated in the RCM. The objective of the RCM was to plan the first phase of the CRP, initiation of the development and validation of methods. Specific objectives were to: Agree upon a small number of veterinary drugs upon which to focus the research; Agree upon analytical methodologies to be employed; formulate individual work plans for each research contract holder within the framework of the overall work plan. Each RC holder presented an overview of residues monitoring from the perspective of their respective countries. Emphasis was placed on problems encountered and future requirements. The participants visited the Austrian National Reference Laboratory for veterinary drug residues at Moedling and discussed the activities there with Mr. Kuhn and laboratory staff. An overall framework for phase of the CRP, focusing upon the compounds and analytical techniques of major importance to the majority of participants, was formulated. Each RC holder discussed and revised their individual work plan with the RA holders and the PO. The overall framework was then reviewed and a summary of the individual work plans presented. Conclusions and recommendations were drafted

  13. Agricultural pesticide residues

    International Nuclear Information System (INIS)

    Fuehr, F.

    1984-01-01

    The utilization of tracer techniques in the study of agricultural pesticide residues is reviewed under the following headings: lysimeter experiments, micro-ecosystems, translocation in soil, degradation of pesticides in soil, biological availability of soil-applied substances, bound residues in the soil, use of macro- and microautography, double and triple labelling, use of tracer labelling in animal experiments. (U.K.)

  14. Formulation Optimization of Sustained-Release Ammonio Methacrylate Copolymer Microspheres. Effects of Log P and Concentration of Polar Cosolvents, and Role of the Drug/Copolymer Ratio

    Directory of Open Access Journals (Sweden)

    Piroska Szabó-Révész

    2011-11-01

    Full Text Available The objectives of this work were the formulation optimization of the preparation process parameters and to evaluate spray-dried sustained-release microspheres using ammonio methacrylate copolymer (AMC as a polymer matrix. The effects of log P and the concentrations of the cosolvents (acetone, methyl ethyl ketone and n-butyl acetate and different drug/copolymer ratios as independent variables on the physicochemical parameters (the W1/O emulsion viscosity, the microsphere production yield, the average particle size, the encapsulation efficiency and the cumulative in vitro drug release as dependent variables were studied. The optimization was carried out on the basis of the 33 factorial design study. The optimization process results showed that addition of polar cosolvents proved effective, linear relationships were observed between the independent and the dependent variables. The best conditions were achieved by microspheres prepared by using a low/medium cosolvent log P, cosolvent concentration of 25–50% v/v and a drug/copolymer ratio of 1:16. The microspheres ensured sustained release with Nernst and Baker-Lonsdale release profiles.

  15. Administration of the non-steroidal anti-inflammatory drug ibuprofen increases macrophage concentrations but reduces necrosis during modified muscle use

    Science.gov (United States)

    Cheung, E. V.; Tidball, J. G.

    2003-01-01

    OBJECTIVE: To test the hypothesis that ibuprofen administration during modified muscle use reduces muscle necrosis and invasion by select myeloid cell populations. METHODS: Rats were subjected to hindlimb unloading for 10 days, after which they experienced muscle reloading by normal weight-bearing to induce muscle inflammation and necrosis. Some animals received ibuprofen by intraperitoneal injection 8 h prior to the onset of muscle reloading, and then again at 8 and 16 h following the onset of reloading. Other animals received buffer injection at 8 h prior to reloading and then ibuprofen at 8 and 16 h following the onset of reloading. Control animals received buffer only at each time point. Quantitative immunohistochemical analysis was used to assess the presence of necrotic muscle fibers, total inflammatory infiltrate, neutrophils, ED1+ macrophages and ED2+ macrophages at 24 h following the onset of reloading. RESULT: Administration of ibuprofen beginning 8 h prior to reloading caused significant reduction in the concentration of necrotic fibers, but increased the concentration of inflammatory cells in muscle. The increase in inflammatory cells was attributable to a 2.6-fold increase in the concentration of ED2+ macrophages. Animals treated with ibuprofen 8 h following the onset of reloading showed no decrease in muscle necrosis or increase in ED2+ macrophage concentrations. CONCLUSION: Administration of ibuprofen prior to increased muscle loading reduces muscle damage, but increases the concentration of macrophages that express the ED2 antigen. The increase in ED2+ macrophage concentration and decrease in necrosis may be mechanistically related because ED2+ macrophages have been associated with muscle regeneration and repair.

  16. Monitoring antibiotic residues in honey

    Directory of Open Access Journals (Sweden)

    Monica Cristina Cara,

    2011-12-01

    Full Text Available Next to the beta-lactam antibiotics in veterinary medicine, streptomycin is one of the mostly used antibiotics. High concentration of streptomycin could lead to ototoxic and nephrotoxic effects. Low concentration – as found in food – may cause allergies, destroy the intestinal flora and favor immunity to some pathogenic microorganisms. In 1948 chlortetracycline was isolated by Duggan as a metabolite and this was the first antibiotic substance of the group of tetracyclines. In the present paper there are presented the monitoring of the antibiotic residues in honey from Timis County. The residues of tetracycline and streptomycin in honey were determined by the method ELISA – a quantitative method of detection. The microtitre wells are coated with tetracycline and anti-streptomycin antibodies. Free antibiotic and immobilized antibiotic compete with the added antibiotic antibody (competitive immunoassay reaction. Any unbound antibody is then removed in a washing step. Bound conjugate enzymes convert the colorless chromogen into a blue product. The addition ofthe stop reagent leads to a color change from blue to yellow. The measurement is made photometrically at 450 nm. The absorption is inversely proportional to the antibiotic concentration in the sample.

  17. Antibiotic residues in broiler and layer meat in Chittagong district of Bangladesh

    Directory of Open Access Journals (Sweden)

    Sarmina Sattar

    2014-09-01

    Full Text Available Aim: The present study was described thin layer chromatography (TLC and ultra-high performance liquid chromatography (UHPLC method for the detection of antibacterial substances in poultry muscle (breast and thigh, kidney, and liver. Materials and Methods: TLC method was used for screening detection of tetracycline, amoxicillin, ciprofloxacin, and enrofloxacin residues in poultry tissues. The samples were extracted with trichloroacetic acid (30%, diethyl ether, followed by detection in pre-coated TLC paper on ultraviolet detector. The UHPLC method was used for the quantification of antimicrobial residues in poultry tissues. Results: The residues of tetracycline were 48% in livers, 24% in kidneys, 20% in thigh muscles, and 24% in breast muscles. Ciprofloxacin residues were found 44% in liver, 42% in kidneys, 34% in thigh muscles and 30% in breast muscles. Enrofloxacin residues were found 40% in liver, 34% in kidneys, 22% in thigh muscles, and 18% in breast muscles. Amoxicillin residues were found 42% in liver, 30% in kidneys, 26% in thigh muscles and 22% in breast muscles. Most of the cases highest residues were found in liver such as tetracycline (48%, ciprofloxacin (44%, enrofloxacin (40% and amoxicillin (42% and almost lowest in breast muscles. In addition, nine positive samples from broiler were selected for amoxicillin residue quantification by UHPLC. It was observed that the concentration of amoxicillin residue in liver was ranging from 16.92 μg/kg to 152.62 μg/kg and in breast muscle was 45.38 μg/kg to 60.55 μg/kg, respectively. The maximum and minimum peak time was 4.7-5.2 min. Among the poultry tissues, liver had the highest level of antibiotic residues in comparison to other samples but the variation was not significant (p>0.05. Conclusions: Evidence suggests that more judicious use of antimicrobials in food animals will reduce the selection of resistant bacteria and help to preserve these valuable drugs for both human and veterinary

  18. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    ... metabolism and its impact on patient welfare. After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolizing systems operate and how they impact upon drug concentration...

  19. Drug composition matters: the influence of carrier concentration on the radiochemical purity, hydroxyapatite affinity and in-vivo bone accumulation of the therapeutic radiopharmaceutical 188Rhenium-HEDP.

    Science.gov (United States)

    Lange, R; de Klerk, J M H; Bloemendal, H J; Ramakers, R M; Beekman, F J; van der Westerlaken, M M L; Hendrikse, N H; Ter Heine, R

    2015-05-01

    (188)Rhenium-HEDP is an effective bone-targeting therapeutic radiopharmaceutical, for treatment of osteoblastic bone metastases. It is known that the presence of carrier (non-radioactive rhenium as ammonium perrhenate) in the reaction mixture during labeling is a prerequisite for adequate bone affinity, but little is known about the optimal carrier concentration. We investigated the influence of carrier concentration in the formulation on the radiochemical purity, in-vitro hydroxyapatite affinity and the in-vivo bone accumulation of (188)Rhenium-HEDP in mice. The carrier concentration influenced hydroxyapatite binding in-vitro as well as bone accumulation in-vivo. Variation in hydroxyapatite binding with various carrier concentrations seemed to be mainly driven by variation in radiochemical purity. The in-vivo bone accumulation appeared to be more complex: satisfactory radiochemical purity and hydroxyapatite affinity did not necessarily predict acceptable bio-distribution of (188)Rhenium-HEDP. For development of new bisphosphonate-based radiopharmaceuticals for clinical use, human administration should not be performed without previous animal bio-distribution experiments. Furthermore, our clinical formulation of (188)Rhenium-HEDP, containing 10 μmol carrier, showed excellent bone accumulation that was comparable to other bisphosphonate-based radiopharmaceuticals, with no apparent uptake in other organs. Radiochemical purity and in-vitro hydroxyapatite binding are not necessarily predictive of bone accumulation of (188)Rhenium-HEDP in-vivo. The formulation for (188)Rhenium-HEDP as developed by us for clinical use exhibits excellent bone uptake and variation in carrier concentration during preparation of this radiopharmaceutical should be avoided. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Prediction of Tissue to Plasma Concentration Ratios of Drugs in the Rat from Experimentally Estimated Volume of Distribution: Application of Allometry.

    Science.gov (United States)

    Mahmood, Iftekhar

    2017-11-28

    In physiologically based pharmacokinetic (PBPK) models, the most important input parameter is tissue-to-plasma partition coefficient (Kp). Over the years, several empirical methods have been developed to predict Kp in animals. The objective of this study was to propose two allometric methods to predict Kp from experimentally determined in-vivo volume of distribution at steady state (Vss). In one method, Vss was allometrically predicted (using a fixed exponent 1.0 or 0.8) in a given tissue of the rat and then Kp was predicted for that tissue. In another method, an allometric plot (Kp versus Vss) was developed to predict Kp in a tissue of the rat. In total, Kp values were predicted for 46 drugs and 338 tissues. The predicted Kp values by the proposed two methods were compared with the experimentally determined Kp values as well as empirically predicted Kp values by other investigators. Comparison of the predicted Kp values by the two proposed methods with experimentally determined Kp values indicated that 67-72% of the predicted Kp values were within two-fold prediction error. The proposed two allometric methods are slightly more accurate than other empirical methods in their predictive performance for the prediction of tissue Kp values for acidic, weak base and neutral drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Handling of Solid Residues

    International Nuclear Information System (INIS)

    Medina Bermudez, Clara Ines

    1999-01-01

    The topic of solid residues is specifically of great interest and concern for the authorities, institutions and community that identify in them a true threat against the human health and the atmosphere in the related with the aesthetic deterioration of the urban centers and of the natural landscape; in the proliferation of vectorial transmitters of illnesses and the effect on the biodiversity. Inside the wide spectrum of topics that they keep relationship with the environmental protection, the inadequate handling of solid residues and residues dangerous squatter an important line in the definition of political and practical environmentally sustainable. The industrial development and the population's growth have originated a continuous increase in the production of solid residues; of equal it forms, their composition day after day is more heterogeneous. The base for the good handling includes the appropriate intervention of the different stages of an integral administration of residues, which include the separation in the source, the gathering, the handling, the use, treatment, final disposition and the institutional organization of the administration. The topic of the dangerous residues generates more expectation. These residues understand from those of pathogen type that are generated in the establishments of health that of hospital attention, until those of combustible, inflammable type, explosive, radio-active, volatile, corrosive, reagent or toxic, associated to numerous industrial processes, common in our countries in development

  2. Determination of neomycin residues in pasteurized milks produced in some dairy processing establishments in East-Azarbaijan Province, Iran

    Directory of Open Access Journals (Sweden)

    M.H Movassagh

    2014-11-01

    Full Text Available Antibiotic residues in milk have a potential hazard for the consumer and may cause allergic reactions, interference in the intestinal flora that result in development of resistant populations of bacteria, thereby rendering antibiotic treatment ineffective. The aim of this study was to determine neomycin residues in pasteurized milk in East-Azarbaijan province. For this, a total of 200 samples of pasteurized milk produced by five dairy processing establishments of East Azarbaijan province was randomly collected. The samples were obtained over the spring and autumn (100 samples for each season of 2010. First, antibiotic residues were determined by Copan milk test. Afterwards, the competitive ELISA assay was used for the determination of neomycin concentration in positive samples. Of all samples, neomycin residues were observed in 9 and 13 samples and the mean neomycin residues amount were 43.20 ± 8.10 and 26.63±2.08 µg/L in spring and autumn, respectively. According to the limit of neomycin (1500 µg/l in cow raw milk in Iran, despite all the remaining drugs in pasteurized milk, in any of the samples exceeded level of neomycin was not observed.Based on the results, continuousmonitoringofantibiotic residues inmilk samples is recommended.

  3. Drug Facts

    Medline Plus

    Full Text Available ... Why Is It So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug ... Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug ...

  4. Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi

    Science.gov (United States)

    Bell, David J; Wootton, Dan; Mukaka, Mavuto; Montgomery, Jacqui; Kayange, Noel; Chimpeni, Phillips; Hughes, Dyfrig A; Molyneux, Malcolm E; Ward, Steve A; Winstanley, Peter A; Lalloo, David G

    2009-01-01

    Background Sulphadoxine-pyrimethamine (SP) is the only single dose therapy for uncomplicated malaria, but there is widespread resistance. At the time of this study, artemether-lumefantrine (AL) and chlorproguanil-dapsone (CPD), both multi-dose regimes, were considered possible alternatives to SP in Malawi. The aim of this study was to investigate the impact of poor adherence on the effectiveness of AL and CPD. Methods Children ≥12 months and adults with uncomplicated malaria were randomized to receive AL, CPD or SP. Adherence was measured using a questionnaire and electronic monitoring devices, MEMS™, pill bottles that recorded the date and time of opening. Day-7 plasma dapsone or lumefantrine concentrations were measured to examine their relationship with adherence and clinical response. Results 841 patients were recruited. The day-28 adequate clinical and parasitological response (ACPR) rates, using intention to treat analysis (missing data treated as failure), were AL 85.2%, CPD 63.7% and SP 50%. ACPR rates for AL were higher than CPD or SP on days 28 and 42 (p ≤ 0.002 for all comparisons). CPD was more effective than SP on day-28 (p = 0.01), but not day-42. Very high adherence was reported using the questionnaire, 100% for AL treated patients and 99.2% for the CPD group. Only three CPD participants admitted missing any doses. 164/181 (90.6%) of CPD treated patients took all their doses out of the MEMS™ container and they were more likely to have a day-28 ACPR than those who did not take all their medication out of the container, p = 0.024. Only 7/87 (8%) AL treated patients did not take all of their doses out of their MEMS™ container and none had treatment failure. Median day-7 dapsone concentrations were higher in CPD treated patients with ACPR than in treatment failures, p = 0.012. There were no differences in day-7 dapsone or lumefantrine concentrations between those who took all their doses from the MEMS™ container and those who did not. A day-7

  5. Measurement of adherence, drug concentrations and the effectiveness of artemether-lumefantrine, chlorproguanil-dapsone or sulphadoxine-pyrimethamine in the treatment of uncomplicated malaria in Malawi

    Directory of Open Access Journals (Sweden)

    Chimpeni Phillips

    2009-08-01

    Full Text Available Abstract Background Sulphadoxine-pyrimethamine (SP is the only single dose therapy for uncomplicated malaria, but there is widespread resistance. At the time of this study, artemether-lumefantrine (AL and chlorproguanil-dapsone (CPD, both multi-dose regimes, were considered possible alternatives to SP in Malawi. The aim of this study was to investigate the impact of poor adherence on the effectiveness of AL and CPD. Methods Children ≥12 months and adults with uncomplicated malaria were randomized to receive AL, CPD or SP. Adherence was measured using a questionnaire and electronic monitoring devices, MEMS™, pill bottles that recorded the date and time of opening. Day-7 plasma dapsone or lumefantrine concentrations were measured to examine their relationship with adherence and clinical response. Results 841 patients were recruited. The day-28 adequate clinical and parasitological response (ACPR rates, using intention to treat analysis (missing data treated as failure, were AL 85.2%, CPD 63.7% and SP 50%. ACPR rates for AL were higher than CPD or SP on days 28 and 42 (p ≤ 0.002 for all comparisons. CPD was more effective than SP on day-28 (p = 0.01, but not day-42. Very high adherence was reported using the questionnaire, 100% for AL treated patients and 99.2% for the CPD group. Only three CPD participants admitted missing any doses. 164/181 (90.6% of CPD treated patients took all their doses out of the MEMS™ container and they were more likely to have a day-28 ACPR than those who did not take all their medication out of the container, p = 0.024. Only 7/87 (8% AL treated patients did not take all of their doses out of their MEMS™ container and none had treatment failure. Median day-7 dapsone concentrations were higher in CPD treated patients with ACPR than in treatment failures, p = 0.012. There were no differences in day-7 dapsone or lumefantrine concentrations between those who took all their doses from the MEMS™ container and those

  6. Evaluation of the Presence and Levels of Enrofloxacin, Ciprofloxacin, Sulfaquinoxaline and Oxytetracycline in Broiler Chickens after Drug Administration

    Science.gov (United States)

    da Silva, Guilherme Resende; Lanza, Isabela Pereira; Ribeiro, Ana Cláudia dos Santos Rossi; Lana, Ângela Maria Quintão; Lara, Leonardo José Camargos

    2016-01-01

    The depletion times of enrofloxacin and its metabolite ciprofloxacin as well as sulfaquinoxaline and oxytetracycline were evaluated in broiler chickens that had been subjected to pharmacological treatment. The presence and residue levels of these drugs in muscle tissue were evaluated using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method that was validated in this work. The results showed the presence of all antimicrobial residues; however, the presence of residues at concentrations higher than the drugs’ maximum residue limit (MRL) of 100 μg kg-1 was found only during the treatment period for oxytetracycline and until two days after discontinuation of the medication for enrofloxacin, ciprofloxacin and sulfaquinoxaline. It was concluded that the residues of all antimicrobials were rapidly metabolized from the broiler muscles; after four days of withdrawal, the levels were lower than the limit of quantification (LOQ) of the method for the studied analytes. PMID:27846314

  7. [Residual neuromuscular blockade].

    Science.gov (United States)

    Fuchs-Buder, T; Schmartz, D

    2017-06-01

    Even small degrees of residual neuromuscular blockade, i. e. a train-of-four (TOF) ratio >0.6, may lead to clinically relevant consequences for the patient. Especially upper airway integrity and the ability to swallow may still be markedly impaired. Moreover, increasing evidence suggests that residual neuromuscular blockade may affect postoperative outcome of patients. The incidence of these small degrees of residual blockade is relatively high and may persist for more than 90 min after a single intubating dose of an intermediately acting neuromuscular blocking agent, such as rocuronium and atracurium. Both neuromuscular monitoring and pharmacological reversal are key elements for the prevention of postoperative residual blockade.

  8. TENORM: Wastewater Treatment Residuals

    Science.gov (United States)

    Water and wastes which have been discharged into municipal sewers are treated at wastewater treatment plants. These may contain trace amounts of both man-made and naturally occurring radionuclides which can accumulate in the treatment plant and residuals.

  9. Residuation in orthomodular lattices

    Directory of Open Access Journals (Sweden)

    Chajda Ivan

    2017-04-01

    Full Text Available We show that every idempotent weakly divisible residuated lattice satisfying the double negation law can be transformed into an orthomodular lattice. The converse holds if adjointness is replaced by conditional adjointness. Moreover, we show that every positive right residuated lattice satisfying the double negation law and two further simple identities can be converted into an orthomodular lattice. In this case, also the converse statement is true and the corresponence is nearly one-to-one.

  10. Characterization of Hospital Residuals

    International Nuclear Information System (INIS)

    Blanco Meza, A.; Bonilla Jimenez, S.

    1997-01-01

    The main objective of this investigation is the characterization of the solid residuals. A description of the handling of the liquid and gassy waste generated in hospitals is also given, identifying the source where they originate. To achieve the proposed objective the work was divided in three stages: The first one was the planning and the coordination with each hospital center, in this way, to determine the schedule of gathering of the waste can be possible. In the second stage a fieldwork was made; it consisted in gathering the quantitative and qualitative information of the general state of the handling of residuals. In the third and last stage, the information previously obtained was organized to express the results as the production rate per day by bed, generation of solid residuals for sampled services, type of solid residuals and density of the same ones. With the obtained results, approaches are settled down to either determine design parameters for final disposition whether for incineration, trituration, sanitary filler or recycling of some materials, and storage politics of the solid residuals that allow to determine the gathering frequency. The study concludes that it is necessary to improve the conditions of the residuals handling in some aspects, to provide the cleaning personnel of the equipment for gathering disposition and of security, minimum to carry out this work efficiently, and to maintain a control of all the dangerous waste, like sharp or polluted materials. In this way, an appreciable reduction is guaranteed in the impact on the atmosphere. (Author) [es

  11. The relationship between the plasma concentration of blonanserin, and its plasma anti-serotonin 5-HT(2A) activity/anti-dopamine D₂ activity ratio and drug-induced extrapyramidal symptoms.

    Science.gov (United States)

    Suzuki, Hidenobu; Gen, Keishi

    2012-03-01

     Blonanserin is a second-generation antipsychotic that was developed in Japan. We investigated the relationships between plasma concentration, the plasma anti-5-HT(2A) activity/anti-D₂ activity (S/D) ratio and extrapyramidal symptoms (EPS) in blonanserin dosing.  The subjects were 29 outpatients with schizophrenia. We assessed EPS using the Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS). The plasma concentrations were measured by high performance liquid chromatography, and the plasma anti-D₂ and anti-5-HT(2A) activities were measured by [³H]-spiperone and [³H]-ketanserin radioreceptor assays. The results revealed that there were significant correlations between both the plasma concentration and the DIEPSS total score (Pblonanserin is mainly determined by plasma concentration, but the incidence of EPS may be inhibited when anti-5HT(2A) activity is predominant over anti-D₂ activity. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.

  12. Detection of pyridaben residue levels in hot pepper fruit and leaves by liquid chromatography-tandem mass spectrometry: effect of household processes.

    Science.gov (United States)

    Kim, Sung-Woo; Abd El-Aty, A M; Rahman, Md Musfiqur; Choi, Jeong-Heui; Choi, Ok-Ja; Rhee, Gyu-Seek; Chang, Moon-Ik; Kim, Heejung; Abid, Morad D N; Shin, Sung Chul; Shim, Jae-Han

    2015-07-01

    Following quick, easy, cheap, effective, rugged and safe (QuEChERS) and LC/MS/MS analysis, pyridaben residual levels were determined in unprocessed and processed hot pepper fruit and leaves. The linearities were satisfactory with determination coefficients (R(2)) in excess of 0.995 in processed and unprocessed pepper fruit and leaves. Recoveries at various concentrations were 79.9-105.1% with relative standard deviations ≤15%. The limits of quantitation of 0.003-0.012 mg/kg were very low compared with the maximum residue limits (2-5 mg/kg) set by the Ministry of Food and Drug Safety, Republic of Korea. The effects of various household processes, including washing, blanching, frying and drying under different conditions (water volume, blanching time and temperature) on residual concentrations were evaluated. Both washing and blanching (in combination with high water volume and time factor) significantly reduced residue levels in hot pepper fruit and leaves compared with other processes. In sum, the developed method was satisfactory and could be used to accurately detect residues in unprocessed and processed pepper fruit and leaves. It is recommended that pepper fruit/leaves be blanched after washing before being consumed to protect consumers from the negative health effects of detected pesticide residues. Copyright © 2014 John Wiley & Sons, Ltd.

  13. Comparison of ractopamine residue depletion from internal tissues.

    Science.gov (United States)

    Pleadin, J; Vulić, A; Perši, N; Terzić, S; Andrišić, M; Zarković, I; Sandor, K; Perak, E

    2013-02-01

    The aim of the study was to compare residue depletion of ractopamine HCl as a β-adrenergic agonist that promotes muscle growth of animals, from internal tissues on days after its repeat administration to animals. The experiment was carried out in 38 albino guinea pigs. Treated animals (n = 30) were orally administered ractopamine HCl in a dose of 3.5 mg/kg body mass per day for 7 consecutive days. On days 1, 10, 20 and 30 of drug discontinuation, animals were randomly sacrificed and the liver, kidney, lung, heart, muscle, spleen and fat samples were collected. In all matrices, ractopamine concentration was determined using validated enzyme-linked immunosorbent assay (ELISA) as a quantitative screening method. The highest ractopamine concentration was recorded on day 1 in the lungs (55.80 ± 15.62 μg/kg), followed by the kidney (21.85 ± 3.91 μg/kg), spleen (12.59 ± 1.95 μg/kg), fat (10.17 ± 5.02 μg/kg), heart (9.73 ± 0.22 μg/kg), liver (5.58 ± 2.09 μg/kg), and lowest in muscle (2.21 ± 1.02 μg/kg). Ractopamine residues were detected in the lungs in the period of 30 days after withdrawal in significantly higher concentrations in comparison to other investigated matrices, suggesting that depletion of ractopamine from the lungs occurs at a much slower rate than its depletion from other internal tissues.

  14. Pesticide residues in locally available cereals and vegetables

    International Nuclear Information System (INIS)

    Cunanan, S.A.; Santos, F.L.; Bonoan, L.S.

    1976-03-01

    Vegetable samples (pechay, cabbage, lettuce, green beans and tomatoes) bought from public markets in the Metro Manila area were analyzed for pesticide residues using gas chromatography. The samples analyzed in 1968-69 contained high levels of chlorinated pesticides such as DDT, Aldrin, Endrin, and Thiodan, while in the samples analyzed in January 1976, no chlorinated and organophosphate pesticides were detected. Cereal samples (rice, corn and sorghum) were obtained from the National Grains Authority and analyzed for pesticide residues and bromine residues. Total bromine residues was determined by neutron activation analysis. In most of the samples analyzed, the concentrations of pesticide residues were below the tolerance levels set by the FAO/WHO Committee on Pesticide Residues in Foods. An exception was one rice sample from Thailand, the bromine residue content (110ppm) of which exceeds the tolerance level of 50ppm

  15. Drug Facts

    Medline Plus

    Full Text Available ... Facts Search form Search Menu Home Drugs That People Abuse Alcohol Facts Bath Salts Facts Cocaine (Coke, ... Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug Use and Kids ...

  16. Drug Facts

    Medline Plus

    Full Text Available ... Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to Quit Drugs? ... Drug Use and Other People Drug Use and Families Drug Use and Kids Drug Use and Unborn ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... People Drug Use and Families Drug Use and Kids Drug Use and Unborn Children Drug Use and ... Children and Teens Stay Drug-Free Talking to Kids About Drugs: What to Say if You Used ...

  18. Management of NORM Residues

    International Nuclear Information System (INIS)

    2013-06-01

    The IAEA attaches great importance to the dissemination of information that can assist Member States in the development, implementation, maintenance and continuous improvement of systems, programmes and activities that support the nuclear fuel cycle and nuclear applications, and that address the legacy of past practices and accidents. However, radioactive residues are found not only in nuclear fuel cycle activities, but also in a range of other industrial activities, including: - Mining and milling of metalliferous and non-metallic ores; - Production of non-nuclear fuels, including coal, oil and gas; - Extraction and purification of water (e.g. in the generation of geothermal energy, as drinking and industrial process water; in paper and pulp manufacturing processes); - Production of industrial minerals, including phosphate, clay and building materials; - Use of radionuclides, such as thorium, for properties other than their radioactivity. Naturally occurring radioactive material (NORM) may lead to exposures at some stage of these processes and in the use or reuse of products, residues or wastes. Several IAEA publications address NORM issues with a special focus on some of the more relevant industrial operations. This publication attempts to provide guidance on managing residues arising from different NORM type industries, and on pertinent residue management strategies and technologies, to help Member States gain perspectives on the management of NORM residues

  19. Dietary exposure assessment of ß-lactam antibiotic residues in milk on Croatian market

    Directory of Open Access Journals (Sweden)

    D. Bažulić

    2012-01-01

    Full Text Available This paper presents the preliminary screening report of the occurrence of β-lactam antibiotic residues in milk on Croatian market. The intensive animal production sometimes leads to the unavoidable presence of residues of veterinary drugs in food. However, it is possible to reduce the presence of residues in foods of animal origin by using the principles of good veterinary and good manufacturing practices, continuous control of food and using risk assessment approach. Method used for determination of these antibiotics were validated according to the guidelines laid down by European Commission Decision 2002/657/EC. The estimated dietary exposure based on the data on average consumption of milk and the estimated concentration of amoxicillin, ampicillin, benzylpenicillin, cloxacillin, cephapirin, cefazolin, cefoperazone and ceftiofur does not exceed relevant toxicological reference value (acceptable daily intake. These indicate that milk on Croatian market contain very low levels of β-lactam antibiotic residues and toxsicological risk with regard to consuming of milk could not be considered as a public health problem.

  20. Residues Of Streptomycin Antibiotic In Commercial Layers In ...

    African Journals Online (AJOL)

    Some of the muscle samples recorded residue concentration levels higher than the W.H.O recommended maximum residue level for streptomycin antibiotic in muscle tissue of food animals. In view of the importance of antibiotics in the treatment of bacterial diseases in both human and animals, it is advocated that the use of ...

  1. Nitrogen mineralization from organic residues: research opportunities.

    Science.gov (United States)

    Cabrera, M L; Kissel, D E; Vigil, M F

    2005-01-01

    Research on nitrogen (N) mineralization from organic residues is important to understand N cycling in soils. Here we review research on factors controlling net N mineralization as well as research on laboratory and field modeling efforts, with the objective of highlighting areas with opportunities for additional research. Among the factors controlling net N mineralization are organic composition of the residue, soil temperature and water content, drying and rewetting events, and soil characteristics. Because C to N ratio of the residue cannot explain all the variability observed in N mineralization among residues, considerable effort has been dedicated to the identification of specific compounds that play critical roles in N mineralization. Spectroscopic techniques are promising tools to further identify these compounds. Many studies have evaluated the effect of temperature and soil water content on N mineralization, but most have concentrated on mineralization from soil organic matter, not from organic residues. Additional work should be conducted with different organic residues, paying particular attention to the interaction between soil temperature and water content. One- and two-pool exponential models have been used to model N mineralization under laboratory conditions, but some drawbacks make it difficult to identify definite pools of mineralizable N. Fixing rate constants has been used as a way to eliminate some of these drawbacks when modeling N mineralization from soil organic matter, and may be useful for modeling N mineralization from organic residues. Additional work with more complex simulation models is needed to simulate both gross N mineralization and immobilization to better estimate net N mineralized from organic residues.

  2. Residual-stress measurements

    Energy Technology Data Exchange (ETDEWEB)

    Ezeilo, A.N.; Webster, G.A. [Imperial College, London (United Kingdom); Webster, P.J. [Salford Univ. (United Kingdom)

    1997-04-01

    Because neutrons can penetrate distances of up to 50 mm in most engineering materials, this makes them unique for establishing residual-stress distributions non-destructively. D1A is particularly suited for through-surface measurements as it does not suffer from instrumental surface aberrations commonly found on multidetector instruments, while D20 is best for fast internal-strain scanning. Two examples for residual-stress measurements in a shot-peened material, and in a weld are presented to demonstrate the attractive features of both instruments. (author).

  3. Rhenium concentration during petroleum deasphalting

    International Nuclear Information System (INIS)

    Troshkina, I.D.; Bel'kova, M.N.

    1994-01-01

    Rhenium distribution and concentration during fractional distillation of certain types of petroleum and natural bitumens from Tatarstan are studied. Rhenium concentration in the process of oil deasphalting is examined for petroleum produced by different techniques, as well as for heavy residues from petroleum distillation. Optimum conditions for the process are revealed fractions of resinous-asphaltene substances concentrating rhenium compounds are found. 5 refs., 3 tabs

  4. Forest residues in cattle feed

    Directory of Open Access Journals (Sweden)

    João Elzeário Castelo Branco Iapichini

    2012-12-01

    Full Text Available The ruminants are capable of converting low-quality food, when they are complementes with high-energy source. Through the use of regional agricultural residues is possible to conduct more economical production systems, since energetic foods have high cost in animal production. There is very abundant availability of residues in agroforestry activities worldwide, so that if a small fraction of them were used with appropriate technical criteria they could largely meet the needs of existing herds in the world and thus meet the demands of consumption of protein of animal origin. The Southwest Region of São Paulo State has large area occupied by reforestation and wide availability of non-timber forest residues, which may represent more concentrated energetic food for ruminant production. This experiment aimed to evaluate the acceptability of ground pine (20, 30 and 40%, replacing part of the energetic food (corn, present in the composition of the concentrate and was performed at the Experimental Station of Itapetininga - Forest Institute / SMA, in the dry season of 2011. It were used four crossbred steers, mean 18 months old, average body weight of 250 kg, housed in a paddock provided with water ad libitum and covered troughs for supplementation with the experimental diet. The adjustment period of the animals was of 07 days and the measurement of the levels of consumption, physiological changes, acceptability and physiological parameters were observed during the following 25 days. The concentrate supplement was formulated based on corn (76.2%, Soybean Meal (20%, urea (2%, Ammonium sulfate (0.4%, calcite (1.4%, Mineral Core (1% and finely ground Pine Cone, replacing corn. In preparing food, the formulas were prepared to make them isoproteic/energetic, containing the following nutrient levels: 22% Crude Protein (CP and 79% of Total Nutrients (TDN. The animals received the supplement in three steps for each level of cone replaced, being offered in the

  5. Drug: D08821 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D08821 Drug Concentrated human red blood cells; Red cells concentrates -leukocytes... reduced (RCC-LR) (TN); Irradiated red cells concentrates -leukocytes reduced (Ir-RCC-LR) (TN) ... PubChem: 96025504 ...

  6. Lindane residues in fish inhabiting Nigerian rivers

    International Nuclear Information System (INIS)

    Okereke, G.U.; Dje, Y.

    1997-01-01

    Analysis for residues of lindane in fish collected from various rivers close to rice agroecosystems showed that the concentrations of lindane ranged from none detectable to 3.4 mg kg -1 . Fish from rivers where strict regulations prohibits its use had no detectable lindane residues while appreciable amounts of lindane were found in fish were such restriction was not enforced with the variation attributed to the extent of use of lindane in the area of contamination. The investigation confirms that the use of lindane in rice production in Nigeria can cause the contamination of fish in nearby rivers. (author). 16 refs, 2 tab

  7. Widespread occurrence of chemical residues in beehive matrices from apiaries located in different landscapes of Western France.

    Directory of Open Access Journals (Sweden)

    Olivier Lambert

    Full Text Available The honey bee, Apis mellifera, is frequently used as a sentinel to monitor environmental pollution. In parallel, general weakening and unprecedented colony losses have been reported in Europe and the USA, and many factors are suspected to play a central role in these problems, including infection by pathogens, nutritional stress and pesticide poisoning. Honey bee, honey and pollen samples collected from eighteen apiaries of western France from four different landscape contexts during four different periods in 2008 and in 2009 were analyzed to evaluate the presence of pesticides and veterinary drug residues.A multi-residue analysis of 80 compounds was performed using a modified QuEChERS method, followed by GC-ToF and LC-MS/MS. The analysis revealed that 95.7%, 72.3% and 58.6% of the honey, honey bee and pollen samples, respectively, were contaminated by at least one compound. The frequency of detection was higher in the honey samples (n = 28 than in the pollen (n = 23 or honey bee (n = 20 samples, but the highest concentrations were found in pollen. Although most compounds were rarely found, some of the contaminants reached high concentrations that might lead to adverse effects on bee health. The three most frequent residues were the widely used fungicide carbendazim and two acaricides, amitraz and coumaphos, that are used by beekeepers to control Varroa destructor. Apiaries in rural-cultivated landscapes were more contaminated than those in other landscape contexts, but the differences were not significant. The contamination of the different matrices was shown to be higher in early spring than in all other periods.Honey bees, honeys and pollens are appropriate sentinels for monitoring pesticide and veterinary drug environmental pollution. This study revealed the widespread occurrence of multiple residues in beehive matrices and suggests a potential issue with the effects of these residues alone or in combination on honey bee health.

  8. Composition of carbonization residues

    Energy Technology Data Exchange (ETDEWEB)

    Hupfer; Leonhardt

    1943-11-27

    This report compared the composition of samples from Wesseling and Leuna. In each case the sample was a residue from carbonization of the residues from hydrogenation of the brown coal processed at the plant. The composition was given in terms of volatile components, fixed carbon, ash, water, carbon, hydrogen, oxygen, nitrogen, volatile sulfur, and total sulfur. The result of carbonization was given in terms of (ash and) coke, tar, water, gas and losses, and bitumen. The composition of the ash was given in terms of silicon dioxide, ferric oxide, aluminum oxide, calcium oxide, magnesium oxide, potassium and sodium oxides, sulfur trioxide, phosphorus pentoxide, chlorine, and titanium oxide. The most important difference between the properties of the two samples was that the residue from Wesseling only contained 4% oil, whereas that from Leuna had about 26% oil. Taking into account the total amount of residue processed yearly, the report noted that better carbonization at Leuna could save 20,000 metric tons/year of oil. Some other comparisons of data included about 33% volatiles at Leuna vs. about 22% at Wesseling, about 5 1/2% sulfur at Leuna vs. about 6 1/2% at Leuna, but about 57% ash for both. Composition of the ash differed quite a bit between the two. 1 table.

  9. Designing with residual materials

    NARCIS (Netherlands)

    Walhout, W.; Wever, R.; Blom, E.; Addink-Dölle, L.; Tempelman, E.

    2013-01-01

    Many entrepreneurial businesses have attempted to create value based on the residual material streams of third parties. Based on ‘waste’ materials they designed products, around which they built their company. Such activities have the potential to yield sustainable products. Many of such companies

  10. DDT residues in sediments from the Bay of Bengal

    Digital Repository Service at National Institute of Oceanography (India)

    Sarkar, A.; SenGupta, R.

    in the sediments from the Bay of Bengal. Peterson grab and hydrographic winch was used to collect the sediment samples. Each sample was extracted and cleaned. Residues were detected by electron capture gas chromatography. A range variation in the concentration...

  11. Concentration device

    DEFF Research Database (Denmark)

    2013-01-01

    A concentration device (2) for filter filtration concentration of particles (4) from a volume of a fluid (6). The concentration device (2) comprises a filter (8) configured to filter particles (4) of a predefined size in the volume of the fluid (6). The concentration device (2) comprises...

  12. Tissue distribution and residue depletion of metronidazole in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Mitrowska, Kamila; Pekala, Agnieszka; Posyniak, Andrzej

    2015-01-01

    Tissue distribution and residue depletion of metronidazole (MNZ) was studied in rainbow trout (Oncorhynchus mykiss) following oral administration of MNZ in feed at the average dose of 25 mg kg(-1) body weight day(-1) for 7 days at 11 ± 2°C. The MNZ concentration in feed was 0.25% while daily feed intake was 1% of body weight. The concentrations of MNZ and its main metabolite, hydroxymetronidazole (MNZOH), in fish tissues were determined by LC-MS/MS. The drug was well distributed in tissues with maximum concentrations on day 1 post-administration. At this time, the mean MNZ concentrations in muscle, skin, kidney, liver and gill were 14,999, 20,269, 15,070, 10,102 and 16,467 µg kg(-1) respectively. MNZ was converted into MNZOH with the ratio of MNZOH:MNZ up to 7% in all fish tissues throughout the withdrawal period. This shows that MNZ itself is the main residue in rainbow trout. MNZ was detected at the level close to the decision limit (0.20 µg kg(-1)) in muscle, skin and muscle with adhering skin up to 42 days, while in kidney, liver and gill it was up to 28 days post-administration. MNZOH was eliminated more rapidly from fish tissues and it was present in muscle alone up to 21 days. The elimination half-lives of MNZ and MNZOH in rainbow trout tissues were 1.83-2.53 and 1.24-2.12 days, respectively. When muscle without skin was analysed, higher MNZ and MNZOH concentrations were detected, and for a longer period of time, than in muscle with adhering skin. Thus muscle alone could be more appropriate for the effective residue control of MNZ in rainbow trout. For the same reason, it is also essential to ensure direct cooling immediately after sampling, since MNZ and its metabolite degrade in fish muscle and skin stored in non-freezing conditions.

  13. Drug diffusion across skin with diffusivity spatially modulated

    Science.gov (United States)

    Montoya Arroyave, Isabel

    2014-05-01

    A diffusion and delivery model of a drug across the skin with diffusivity spatially modulated is formulated and solved analytically using computer algebra. The model is developed using one-dimensional diffusion equation with a diffusivity which is a function of position in the skin; with an initial condition which is describing that the drug is initially contained inside a therapeutic patch; with a boundary condition according to which the change in concentration in the patch is minimal, such that assumption of zero flux at the patch-skin interface is valid; and with other boundary condition according to which the microcirculation in the capillaries just below the dermis carries the drug molecules away from the site at a very fast rate, maintaining the inner concentration at 0. The model is solved analytically by the method of the Laplace transform, with Bromwich integral and residue theorem. The concentration profile of the drug in the skin is expressed as an infinite series of Bessel functions. The corresponding total amount of delivered drug is expressed as an infinite series of decreasing exponentials. Also, the corresponding effective time for the therapeutic patch is determined. All computations were performed using computer algebra software, specifically Maple. The analytical results obtained are important for understanding and improving currentapplications of therapeutic patches. For future research it is interesting to consider more general models of spatial modulation of the diffusivity and the possible application of other computer algebra software such as Mathematica and Maxima.

  14. Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

    Energy Technology Data Exchange (ETDEWEB)

    Slatter, J.G. [Pharmacia Corp., Peapack, NJ (United States); Sams, J.P.; Easter, J.A. [Pharmacia Corp., Kalamazoo, MI (United States)] [and others

    2003-05-01

    Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [{sup 14}C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [{sup 14}C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [{sup 14}C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled {sup 14}CO{sub 2}. After 7 daily [{sup 14}C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C{sub max} and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

  15. Drug Addiction

    Science.gov (United States)

    ... attempt to stop taking the drug Recognizing unhealthy drug use in family members Sometimes it's difficult to ... sold to support drug use Recognizing signs of drug use or intoxication Signs and symptoms of drug ...

  16. Drug Allergy

    Science.gov (United States)

    ... Seizure Loss of consciousness Other conditions resulting from drug allergy Less common drug allergy reactions occur days ... reaction the first time you take the drug. Drugs commonly linked to allergies Although any drug can ...

  17. Residual stresses in material processing

    Science.gov (United States)

    Kozaczek, K. J.; Watkins, T. R.; Hubbard, C. R.; Wang, Xun-Li; Spooner, S.

    Material manufacturing processes often introduce residual stresses into the product. The residual stresses affect the properties of the material and often are detrimental. Therefore, the distribution and magnitude of residual stresses in the final product are usually an important factor in manufacturing process optimization or component life prediction. The present paper briefly discusses the causes of residual stresses. It then addresses the direct, nondestructive methods of residual stress measurement by X ray and neutron diffraction. Examples are presented to demonstrate the importance of residual stress measurement in machining and joining operations.

  18. Sustainable System for Residual Hazards Management

    International Nuclear Information System (INIS)

    Kevin M. Kostelnik; James H. Clarke; Jerry L. Harbour

    2004-01-01

    Hazardous, radioactive and other toxic substances have routinely been generated and subsequently disposed of in the shallow subsurface throughout the world. Many of today's waste management techniques do not eliminate the problem, but rather only concentrate or contain the hazardous contaminants. Residual hazards result from the presence of hazardous and/or contaminated material that remains on-site following active operations or the completion of remedial actions. Residual hazards pose continued risk to humans and the environment and represent a significant and chronic problem that require continuous long-term management (i.e. >1000 years). To protect human health and safeguard the natural environment, a sustainable system is required for the proper management of residual hazards. A sustainable system for the management of residual hazards will require the integration of engineered, institutional and land-use controls to isolate residual contaminants and thus minimize the associated hazards. Engineered controls are physical modifications to the natural setting and ecosystem, including the site, facility, and/or the residual materials themselves, in order to reduce or eliminate the potential for exposure to contaminants of concern (COCs). Institutional controls are processes, instruments, and mechanisms designed to influence human behavior and activity. System failure can involve hazardous material escaping from the confinement because of system degradation (i.e., chronic or acute degradation) or by external intrusion of the biosphere into the contaminated material because of the loss of institutional control. An ongoing analysis of contemporary and historic sites suggests that the significance of the loss of institutional controls is a critical pathway because decisions made during the operations/remedial action phase, as well as decisions made throughout the residual hazards management period, are key to the long-term success of the prescribed system. In fact

  19. Crop Residue Biomass Effects on Agricultural Runoff

    Directory of Open Access Journals (Sweden)

    Damodhara R. Mailapalli

    2013-01-01

    Full Text Available High residue loads associated with conservation tillage and cover cropping may impede water flow in furrow irrigation and thus decrease the efficiency of water delivery and runoff water quality. In this study, the biomass residue effects on infiltration, runoff, and export of total suspended solids (TSS, dissolved organic carbon (DOC, sediment-associated carbon (TSS-C, and other undesirable constituents such as phosphate (soluble P, nitrate (, and ammonium ( in runoff water from a furrow-irrigated field were studied. Furrow irrigation experiments were conducted in 91 and 274 m long fields, in which the amount of residue in the furrows varied among four treatments. The biomass residue in the furrows increased infiltration, and this affected total load of DOC, TSS, and TSS-C. Net storage of DOC took place in the long but not in the short field because most of the applied water ran off in the short field. Increasing field length decreased TSS and TSS-C losses. Total load of , , and soluble P decreased with increasing distance from the inflow due to infiltration. The concentration and load of P increased with increasing residue biomass in furrows, but no particular trend was observed for and . Overall, the constituents in the runoff decreased with increasing surface cover and field length.

  20. SRC Residual fuel oils

    Science.gov (United States)

    Tewari, Krishna C.; Foster, Edward P.

    1985-01-01

    Coal solids (SRC) and distillate oils are combined to afford single-phase blends of residual oils which have utility as fuel oils substitutes. The components are combined on the basis of their respective polarities, that is, on the basis of their heteroatom content, to assure complete solubilization of SRC. The resulting composition is a fuel oil blend which retains its stability and homogeneity over the long term.

  1. Recovery of silver residues from dental amalgam.

    Science.gov (United States)

    Pereira, Heloísa Aparecida Barbosa da Silva; Iano, Flávia Godoy; da Silva, Thelma Lopes; de Oliveira, Rodrigo Cardoso; de Menezes, Manoel Lima; Buzalaf, Marília Afonso Rabelo

    2010-01-01

    Dental amalgam residues are probably the most important chemical residues generated from clinical dental practice because of the presence of heavy metals among its constituents, mainly mercury and silver. The purpose of this study was to develop an alternative method for the recovery of silver residues from dental amalgam. The residue generated after vacuum distillation of dental amalgam for the separation of mercury was initially diluted with 32.5% HNO3, followed by precipitation with 20% NaCl. Sequentially, under constant heating and agitation with NaOH and sucrose, the sample was reduced to metallic silver. However, the processing time was too long, which turned this procedure not viable. In another sequence of experiments, the dilution was accomplished with concentrated HNO3 at 90 degrees C, followed by precipitation with 20% NaCl. After washing, the pellet was diluted with concentrated NH4OH, water and more NaCl in order to facilitate the reaction with the reducer. Ascorbic acid was efficiently used as reducer, allowing a fast reduction, thus making the procedure viable. The proposed methodology is of easy application and does not require sophisticated equipment or expensive reagents.

  2. Recovery of silver residues from dental amalgam

    Directory of Open Access Journals (Sweden)

    Heloísa Aparecida Barbosa da Silva Pereira

    2010-04-01

    Full Text Available Dental amalgam residues are probably the most important chemical residues generated from clinical dental practice because of the presence of heavy metals among its constituents, mainly mercury and silver. OBJECTIVE: The purpose of this study was to develop an alternative method for the recovery of silver residues from dental amalgam. MATERIAL AND METHODS: The residue generated after vacuum distillation of dental amalgam for the separation of mercury was initially diluted with 32.5% HNO3, followed by precipitation with 20% NaCl. Sequentially, under constant heating and agitation with NaOH and sucrose, the sample was reduced to metallic silver. However, the processing time was too long, which turned this procedure not viable. In another sequence of experiments, the dilution was accomplished with concentrated HNO3 at 90ºC, followed by precipitation with 20% NaCl. After washing, the pellet was diluted with concentrated NH4OH, water and more NaCl in order to facilitate the reaction with the reducer. RESULTS: Ascorbic acid was efficiently used as reducer, allowing a fast reduction, thus making the procedure viable. CONCLUSIONS: The proposed methodology is of easy application and does not require sophisticated equipment or expensive reagents.

  3. Composition of carbonization residues

    Energy Technology Data Exchange (ETDEWEB)

    Hupfer; Leonhardt

    1943-11-30

    This report gave a record of the composition of several samples of residues from carbonization of various hydrogenation residue from processing some type of coal or tar in the Bergius process. These included Silesian bituminous coal processed at 600 atm. with iron catalyst, in one case to produce gasoline and middle oil and in another case to produce heavy oil excess, Scholven coal processed at 250 atm. with tin oxalate and chlorine catalyst, Bruex tar processed in a 10-liter oven using iron catalyst, and a pitch mixture from Welheim processed in a 10-liter over using iron catalyst. The values gathered were compared with a few corresponding values estimated for Boehlen tar and Gelsenberg coal based on several assumptions outlined in the report. The data recorded included percentage of ash in the dry residue and percentage of carbon, hydrogen, oxygen, nitrogen, chlorine, total sulfur, and volatile sulfur. The percentage of ash varied from 21.43% in the case of Bruex tar to 53.15% in the case of one of the Silesian coals. Percentage of carbon varied from 44.0% in the case of Scholven coal to 78.03% in the case of Bruex tar. Percentage of total sulfur varied from 2.28% for Bruex tar to a recorded 5.65% for one of the Silesian coals and an estimated 6% for Boehlen tar. 1 table.

  4. Concentration risk

    Directory of Open Access Journals (Sweden)

    Matić Vesna

    2016-01-01

    Full Text Available Concentration risk has been gaining a special dimension in the contemporary financial and economic environment. Financial institutions are exposed to this risk mainly in the field of lending, mostly through their credit activities and concentration of credit portfolios. This refers to the concentration of different exposures within a single risk category (credit risk, market risk, operational risk, liquidity risk.

  5. Pesticide residues in birds and mammals

    Science.gov (United States)

    Stickel, L.F.; Edwards, C.A.

    1973-01-01

    exposure to an organochlorine pesticide, the concentrations of residues in the different tissues are ordinarily directly correlated with each other. When the dosage is at lethal levels, or when stored residues are mobilised to lethal levels, the balanced relationship is disrupted. The concentrations of residues in the brain provide the most rigorous criteria for diagnosis of death due to these chemicals, and levels are generally similar across a wide range of species of birds and mammals. Residues in liver are closely correlated with recent dose, either from direct intake or from mobilisation from storage, and so reflect hazardous exposure. Residues in the whole carcass show the storage reserve, and so indicate the potential for adverse effects from lethal mobilisation or from the continuous slow mobilisation that occurs during the normal processes of metabolism and excretion. A synchronous, rapid, and widespread decline in weight and thickness of shells of eggs laid by many species of wild birds occurred in the late 1940's and has persisted. Birds of prey were primarily affected; exceptions apparently are the result of lesser exposure because of different food habits. Many species of fish-eating birds are also affected. Others, however, appear to be more resistant and to accumulate much higher residues before shell-thinning occurs. Seed-eating birds do not appear to have been generally affected; their exposure is ordinarily lower, but physiological factors also seem to be involved. A relationship between shell-thinning and population decline has been established for many species. In exceptional cases, such as the herring gull, persistent re-nesting and other population reactions have overcome adverse effects at the population level. The discovery of shell-thinning among natural populations, and the hypothesis that this thinning was related to the occurrence of organochlorine pesticides, stimulated experimental studies to determine wheth

  6. Drug-Target Kinetics in Drug Discovery.

    Science.gov (United States)

    Tonge, Peter J

    2018-01-17

    The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

  7. Drug Facts

    Medline Plus

    Full Text Available ... some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely ... So Hard to Quit Drugs? Effects of Drugs Drug Use and Other People Drug Use and Families Drug ...

  8. Human-use antibacterial residues in the natural environment of China: implication for ecopharmacovigilance.

    Science.gov (United States)

    Wang, Jun; He, Bingshu; Hu, Xiamin

    2015-06-01

    Antibacterial residues in the natural environment have been of increasing concern due to their impact on bacteria resistance development and toxicity to natural communities and ultimately to public health. China is a large country with high production and consumption of antibacterials for its population growth and economic development in recent years. In this article, we summarized the current situation of human-use antibacterial pollution in Chinese water (wastewaters, natural and drinking waters) and solid matrices (sludge, sediment, and soil) reported in 33 peer-reviewed papers. We found that, although there are adequate wastewater treatment systems in China, human-use antibacterial residues in the natural environment were reported almost throughout the whole country. Three most frequently prescribed classes of antibacterials in China, including quinolones, macrolides, and β-lactam, were also the predominant classes of residues in Chinese environment, manifested as the high concentration and detection frequency. In view of this alarming situation, we have presented that ecopharmacovigilance (EPV) might be implemented in the antibacterial drug administration of China, as the active participation of the pharmaceutical industry and drug regulatory authorities from the diffuse source of antibacterial pollution. Considering EPV experience of developed countries together with the actual conditions of China, we have identified some approaches that can be taken, including:• Focus on education;• Further strengthening and persevering the antibacterial stewardship strategies and pharmaceutical take-back programs in China;• Designing greener antibacterials with better degradability in the environment;• Implementing environmental risk assessment prior to launch of new drugs;• Strengthening collaboration in EPV-related areas.

  9. Concentrator Photovoltaics

    CERN Document Server

    Luque, Antonio L

    2007-01-01

    Photovoltaic solar-energy conversion is one of the most promising technologies for generating renewable energy, and conversion of concentrated sunlight can lead to reduced cost for solar electricity. In fact, photovoltaic conversion of concentrated sunlight insures an efficient and cost-effective sustainable power resource. This book gives an overview of all components, e.g. cells, concentrators, modules and systems, for systems of concentrator photovoltaics. The authors report on significant results related to design, technology, and applications, and also cover the fundamental physics and market considerations. Specific contributions include: theory and practice of sunlight concentrators; an overview of concentrator PV activities; a description of concentrator solar cells; design and technology of modules and systems; manufacturing aspects; and a market study.

  10. Drug allergies

    Science.gov (United States)

    Allergic reaction - drug (medication); Drug hypersensitivity; Medication hypersensitivity ... A drug allergy involves an immune response in the body that produces an allergic reaction to a medicine. The ...

  11. Quadratic residues and non-residues selected topics

    CERN Document Server

    Wright, Steve

    2016-01-01

    This book offers an account of the classical theory of quadratic residues and non-residues with the goal of using that theory as a lens through which to view the development of some of the fundamental methods employed in modern elementary, algebraic, and analytic number theory. The first three chapters present some basic facts and the history of quadratic residues and non-residues and discuss various proofs of the Law of Quadratic Reciprosity in depth, with an emphasis on the six proofs that Gauss published. The remaining seven chapters explore some interesting applications of the Law of Quadratic Reciprocity, prove some results concerning the distribution and arithmetic structure of quadratic residues and non-residues, provide a detailed proof of Dirichlet’s Class-Number Formula, and discuss the question of whether quadratic residues are randomly distributed. The text is a valuable resource for graduate and advanced undergraduate students as well as for mathematicians interested in number theory.

  12. Carbon Concentration of Austenite

    Directory of Open Access Journals (Sweden)

    Z. Ławrynowicz

    2007-07-01

    Full Text Available The investigation was carried out to examine the influence of temperature and times of austempering process on the maximum extend towhich the bainite reaction can proceed and the carbon content in retained austenite. It should be noted that a small percentage change in theaustenite carbon content can have a significant effect on the subsequent austempering reaction changing the volume fraction of the phasespresent and hence, the resulting mechanical properties. Specimens were prepared from an unalloyed ductile cast iron, austenitised at 950oCfor 60 minutes and austempered by the conventional single-step austempering process at four temperatures between BS and MS, eg., 250,300, 350 and 400oC. The samples were austempered at these temperatures for 15, 30, 60, 120 and 240 minutes and finally quenched toambient temperature. Volume fractions of retained austenite and carbon concentration in the residual austenite have been observed byusing X-ray diffraction. Additionally, carbon concentration in the residual austenite was calculated using volume fraction data of austeniteand a model developed by Bhadeshia based on the McLellan and Dunn quasi-chemical thermodynamic model. The comparison ofexperimental data with the T0, T0' and Ae3' phase boundaries suggests the likely mechanism of bainite reaction in cast iron is displacive rather than diffusional. The carbon concentration in retained austenite demonstrates that at the end of bainite reaction the microstructure must consist of not only ausferrite but additionally precipitated carbides.

  13. Sharing Residual Liability

    DEFF Research Database (Denmark)

    Carbonara, Emanuela; Guerra, Alice; Parisi, Francesco

    2016-01-01

    Economic models of tort law evaluate the efficiency of liability rules in terms of care and activity levels. A liability regime is optimal when it creates incentives to maximize the value of risky activities net of accident and precaution costs. The allocation of primary and residual liability...... the virtues and limits of loss-sharing rules in generating optimal (second-best) incentives and allocations of risk. We find that loss sharing may be optimal in the presence of countervailing policy objectives, homogeneous risk avoiders, and subadditive risk, which potentially offers a valuable tool...

  14. Illegal drugs and delinquency.

    Science.gov (United States)

    Kirschbaum, Katrin M; Grigoleit, Lisa; Hess, Cornelius; Madea, Burkhard; Musshoff, Frank

    2013-03-10

    An interrelation between consumption of illegal drugs and committing an indictable offence has been repeatedly discussed in literature. In a retrospective study serum concentrations of illegal and legal drugs as well as data originating from police reports and examinations by physicians taking blood from individuals being suspected to be under the influence of drugs were evaluated. Results from 4816 cases were available. Property offences were the most frequent type (36%) as well as consumption of cannabinoids (55%). Psychophysiological conditions of consumers were compared with according serum concentrations. Close correlations between stimulating drugs and violence associated crime could not be found. Stimulated as well as sedated behaviour occurring following the consumption of various drugs might be the reason for no clear correlation between types of offence and consumed illegal or legal drugs in this study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  15. Quantification of sodium pentobarbital residues from equine mortality compost piles.

    Science.gov (United States)

    Payne, J; Farris, R; Parker, G; Bonhotal, J; Schwarz, M

    2015-04-01

    Sodium pentobarbital, a euthanasia drug, can persist in animal carcasses following euthanasia and can cause secondary toxicosis to animals that consume the remains. This experiment was conducted to observe the effects of composting on euthanized horse carcass degradation and sodium pentobarbital residues in compost material up to 367 d. Six separate compost bins were constructed on pastureland. Three bins served as the control while 3 served as the treatment. The carbonaceous material, or bulking agent, consisted of hardwood chips mixed with yard waste wetted to approximately 50% moisture content. Bulking agent was added to each bin at a depth of 0.46 m, creating the pad. A licensed veterinarian provided 6 horse carcasses for use in the experiment. These horses had required euthanasia for health reasons. All horses were weighed and then sedated with an intravenous injection of 8 mL of xylazine. After sedation the 3 horses in the treatment group were euthanized by intravenous injection of 60 mL of sodium pentobarbital. The 3 control group horses were anesthetized by intravenous injection of 15 mL of ketamine hydrochloride and then humanely euthanized by precise gunshot to the temporal lobe. Following euthanasia, each carcass was placed on the center of the pad and surrounded with 0.6 m of additional bulking agent. Serum and liver samples were obtained immediately following death. Compost samples were obtained on d 7, 14, 28, 56, 84, 129, 233, and 367 while soil samples were obtained on d -1 and 367. Each sample was analyzed for sodium pentobarbital concentration. Compost pile and ambient temperatures were also recorded. Composting successfully degraded soft tissue with only large bones remaining. Data illustrate that sodium pentobarbital was detectable up to 367 d in compost piles with no clear trend of concentration reduction. Drug residues were detected in soil samples indicating that sodium pentobarbital leached from the carcass and through the pad. These

  16. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Kids Drug Use and Unborn Children Drug Use and Your Health Other Effects on ... Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking to Kids ...

  17. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & ...

  18. Drug Facts

    Medline Plus

    Full Text Available ... Use and Unborn Children Drug Use and Your Health Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug ...

  19. Drug Safety

    Science.gov (United States)

    ... over-the-counter drug. The FDA evaluates the safety of a drug by looking at Side effects ... clinical trials The FDA also monitors a drug's safety after approval. For you, drug safety means buying ...

  20. Drug Facts

    Medline Plus

    Full Text Available ... and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ... Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use ...

  1. Bioenergy from sisal residues

    Energy Technology Data Exchange (ETDEWEB)

    Jungersen, G. [Dansk Teknologisk Inst. (Denmark); Kivaisi, A.; Rubindamayugi, M. [Univ. of Dar es Salaam (Tanzania, United Republic of)

    1998-05-01

    The main objectives of this report are: To analyse the bioenergy potential of the Tanzanian agro-industries, with special emphasis on the Sisal industry, the largest producer of agro-industrial residues in Tanzania; and to upgrade the human capacity and research potential of the Applied Microbiology Unit at the University of Dar es Salaam, in order to ensure a scientific and technological support for future operation and implementation of biogas facilities and anaerobic water treatment systems. The experimental work on sisal residues contains the following issues: Optimal reactor set-up and performance; Pre-treatment methods for treatment of fibre fraction in order to increase the methane yield; Evaluation of the requirement for nutrient addition; Evaluation of the potential for bioethanol production from sisal bulbs. The processing of sisal leaves into dry fibres (decortication) has traditionally been done by the wet processing method, which consumes considerable quantities of water and produces large quantities of waste water. The Tanzania Sisal Authority (TSA) is now developing a dry decortication method, which consumes less water and produces a waste product with 12-15% TS, which is feasible for treatment in CSTR systems (Continously Stirred Tank Reactors). (EG)

  2. Intraoperative neuromuscular monitoring site and residual paralysis.

    Science.gov (United States)

    Thilen, Stephan R; Hansen, Bradley E; Ramaiah, Ramesh; Kent, Christopher D; Treggiari, Miriam M; Bhananker, Sanjay M

    2012-11-01

    Residual paralysis is common after general anesthesia involving administration of neuromuscular blocking drugs (NMBDs). Management of NMBDs and reversal is frequently guided by train-of-four (TOF) monitoring. We hypothesized that monitoring of eye muscles is associated with more frequent residual paralysis than monitoring at the adductor pollicis. This prospective cohort study enrolled 180 patients scheduled for elective surgery with anticipated use of NMBDs. Collected variables included monitoring site, age, gender, weight, body mass index, American Society of Anesthesiologists physical status class, type and duration of surgery, type of NMBDs, last and total dose administered, TOF count at time of reversal, dose of neostigmine, and time interval between last dose of NMBDs to quantitative measurement. Upon postanesthesia care unit admission, we measured TOF ratios by acceleromyography at the adductor pollicis. Residual paralysis was defined as a TOF ratio less than 90%. Multivariable logistic regression was used to account for unbalances between the two groups and to adjust for covariates. 150 patients received NMBDs and were included in the analysis. Patients with intraoperative TOF monitoring of eye muscles had significantly greater incidence of residual paralysis than patients monitored at the adductor pollicis (P paralysis was observed in 51/99 (52%) and 11/51 (22%) of patients, respectively. The crude odds ratio was 3.9 (95% CI: 1.8-8.4), and the adjusted odds ratio was 5.5 (95% CI: 2.1-14.5). Patients having qualitative TOF monitoring of eye muscles had a greater than 5-fold higher risk of postoperative residual paralysis than those monitored at the adductor pollicis.

  3. Albendazole residues in goat's milk: Interferences in microbial inhibitor tests used to detect antibiotics in milk

    Directory of Open Access Journals (Sweden)

    Tamara Romero

    2017-04-01

    Full Text Available Albendazole (ABZ residues in goat's milk and their effect on the response of microbial inhibitor tests used for screening antibiotics were evaluated. A total of 18 Murciano-Granadina goats were treated with ABZ and individually milked once a day over a 7-day period. ABZ quantification was performed by high performance liquid chromatography. The ABZ parent drug was not detected. The maximum concentration of its metabolites (ABZ sulfoxide, ABZ sulfone, and ABZ 2-aminosulfone was reached on the 1st day post treatment (260.0 ± 70.1 μg/kg, 112.8 ± 28.7 μg/kg, 152.0 ± 23.6 μg/kg, respectively, decreasing to lower than the maximum residue limit (MRL, 100 μg/kg on the 3rd day post treatment. Milk samples were also analyzed by microbial tests [Brilliant Black Reduction Test (BRT MRL, Delvotest SP-NT MCS and Eclipse 100], and only one positive result was found for Delvotest SP-NT MCS and Eclipse 100. However, a high occurrence of positive outcomes was obtained for BRT MRL during 6 days post treatment, whereas ABZ residues were not detected from the 4th day post administration, suggesting that factors other than the antiparasitic agent might affect the microbial test response.

  4. Albendazole residues in goat's milk: Interferences in microbial inhibitor tests used to detect antibiotics in milk.

    Science.gov (United States)

    Romero, Tamara; Althaus, Rafael; Moya, Vicente Javier; Beltrán, María Del Carmen; Reybroeck, Wim; Molina, María Pilar

    2017-04-01

    Albendazole (ABZ) residues in goat's milk and their effect on the response of microbial inhibitor tests used for screening antibiotics were evaluated. A total of 18 Murciano-Granadina goats were treated with ABZ and individually milked once a day over a 7-day period. ABZ quantification was performed by high performance liquid chromatography. The ABZ parent drug was not detected. The maximum concentration of its metabolites (ABZ sulfoxide, ABZ sulfone, and ABZ 2-aminosulfone) was reached on the 1 st day post treatment (260.0 ± 70.1 μg/kg, 112.8 ± 28.7 μg/kg, 152.0 ± 23.6 μg/kg, respectively), decreasing to lower than the maximum residue limit (MRL, 100 μg/kg) on the 3 rd day post treatment. Milk samples were also analyzed by microbial tests [Brilliant Black Reduction Test (BRT) MRL, Delvotest SP-NT MCS and Eclipse 100], and only one positive result was found for Delvotest SP-NT MCS and Eclipse 100. However, a high occurrence of positive outcomes was obtained for BRT MRL during 6 days post treatment, whereas ABZ residues were not detected from the 4 th day post administration, suggesting that factors other than the antiparasitic agent might affect the microbial test response. Copyright © 2016. Published by Elsevier B.V.

  5. Development of irradiation technique on controlling food contamination residue

    International Nuclear Information System (INIS)

    Liu Bin; Xiong Shanbai; Xiong Guangquan; Cheng Wei; Chen Yuxia; Liao Tao; Li Xin; Lin Ruotai

    2010-01-01

    The current state of the researches of irradiation technology on controlling food mycotoxin, pesticide, veterinary drugs and fishery drugs residue was summarized. And the degradation rate, mechanism, products and toxicities of food contamination were expatiated. The free radical from irradiation attack the site of weaker bond, and the less or more toxic substances were produced, which lead to the degradation of the food contamination. The limitations and future application of irradiation technique on controlling food contamination were also analyzed. (authors)

  6. The first application of wastewater-based drug epidemiology in five South Korean cities.

    Science.gov (United States)

    Kim, Ki Yong; Lai, Foon Yin; Kim, Hee-Young; Thai, Phong K; Mueller, Jochen F; Oh, Jeong-Eun

    2015-08-15

    Illicit drug consumption in five cities in South Korea was estimated by analyzing 17 drug residues in untreated wastewater samples collected during the Christmas and New Year period of 2012-13. Only methamphetamine, amphetamine, and codeine were detected at concentrations of tens of nanograms per liter or even lower concentrations in more than 90% of the samples. Other illicit drug residues (including cocaine, methadone, and benzoylecgonine) that have been detected frequently in wastewater from other countries were not found in this study. Methamphetamine was found to be the most widely used illicit drug in South Korea, and the estimated average consumption rate was 22 mg d(-1) (1000 people)(-1). This rate is, for example, 2-5 times lower than the estimated average consumption rates in Hong Kong and other parts of China and 4-80 times lower than the estimated average consumption rates in cities in Western countries. It should be noted that the wastewater samples analyzed in this study were collected during a holiday season, when daily consumption of illicit drugs is often higher than on an average day. The methamphetamine usage rates were calculated for different cities in South Korea, and the usage rates in smaller cities was higher (2-4 times) than the average. Copyright © 2015. Published by Elsevier B.V.

  7. Resíduos de azevém na superfície de um Planossolo alagado e seus efeitos na concentração de nutrientes na solução do solo e em plantas de arroz Ryegrass residues on soil surface of a flooded Albaqualf soil and their effects on nutrients concentration in soil solution and rice plants

    Directory of Open Access Journals (Sweden)

    Fábiana Schmidt

    2009-10-01

    with a higher growing and nutrient absorptions. The objectives of this research are to quantify the nutrient absorptions, the rice crop growing, and to determine the concentration of nutrients in the soil solution on a flooding Albaqualf soil. For this, increasing doses of ryegrass residues were applied in the soil surface. A greenhouse experiment was carried out using a randomized complete block design with six doses of ryegrass residues (0.0; 1.25; 2.5; 5.0; 7.5 and 10.0Mg ha-1 applied to the soil surface. Cultivar 'BRS 7 Taim' pre-germinated seeds were sown in plastic pots. The soil in the pots was flooded 15 days after this procedure and plants were hept in this condition for an additional 45 days. In the rice plants were evaluated the dry matter weight of the shoots and the following nutrients: N, K, P, Ca, Mg, Fe, Mn, Cu and Zn. In the soil solution were evaluated the redox potential (Eh, pH, and the concentration of Mn, Fe, K, Ca, Mg. Results show that the addition of increasing doses of ryegrass residues in the flooded soil surface until 10Mg ha-1 strengthened the soil redox reaction process increasing the concentration of Mn, Fe, Ca, Mg and K in the soil solution. It also increased the K and Fe contents in the aerial part of rice plants as well increased their dry matter weight.

  8. Hanford tank residual waste - Contaminant source terms and release models

    International Nuclear Information System (INIS)

    Deutsch, William J.; Cantrell, Kirk J.; Krupka, Kenneth M.; Lindberg, Michael L.; Jeffery Serne, R.

    2011-01-01

    Highlights: → Residual waste from five Hanford spent fuel process storage tanks was evaluated. → Gibbsite is a common mineral in tanks with high Al concentrations. → Non-crystalline U-Na-C-O-P ± H phases are common in the U-rich residual. → Iron oxides/hydroxides have been identified in all residual waste samples. → Uranium release is highly dependent on waste and leachant compositions. - Abstract: Residual waste is expected to be left in 177 underground storage tanks after closure at the US Department of Energy's Hanford Site in Washington State, USA. In the long term, the residual wastes may represent a potential source of contamination to the subsurface environment. Residual materials that cannot be completely removed during the tank closure process are being studied to identify and characterize the solid phases and estimate the release of contaminants from these solids to water that might enter the closed tanks in the future. As of the end of 2009, residual waste from five tanks has been evaluated. Residual wastes from adjacent tanks C-202 and C-203 have high U concentrations of 24 and 59 wt.%, respectively, while residual wastes from nearby tanks C-103 and C-106 have low U concentrations of 0.4 and 0.03 wt.%, respectively. Aluminum concentrations are high (8.2-29.1 wt.%) in some tanks (C-103, C-106, and S-112) and relatively low ( 2 -saturated solution, or a CaCO 3 -saturated water. Uranium release concentrations are highly dependent on waste and leachant compositions with dissolved U concentrations one or two orders of magnitude higher in the tests with high U residual wastes, and also higher when leached with the CaCO 3 -saturated solution than with the Ca(OH) 2 -saturated solution. Technetium leachability is not as strongly dependent on the concentration of Tc in the waste, and it appears to be slightly more leachable by the Ca(OH) 2 -saturated solution than by the CaCO 3 -saturated solution. In general, Tc is much less leachable (<10 wt.% of the

  9. Determination of Pesticides Residues in Cucumbers Grown in Greenhouse and the Effect of Some Procedures on Their Residues.

    Science.gov (United States)

    Leili, Mostafa; Pirmoghani, Amin; Samadi, Mohammad Taghi; Shokoohi, Reza; Roshanaei, Ghodratollah; Poormohammadi, Ali

    2016-11-01

    The objective of this study was to determine the residual concentrations of ethion and imidacloprid in cucumbers grown in greenhouse. The effect of some simple processing procedures on both ethion and imidacloprid residues were also studied. Ten active greenhouses that produce cucumber were randomly selected. Ethion and imidacloprid as the most widely used pesticides were measured in cucumber samples of studied greenhouses. Moreover, the effect of storing, washing, and peeling as simple processing procedures on both ethion and imidacloprid residues were investigated. One hour after pesticide application; the maximum residue levels (MRLs) of ethion and imidacloprid were higher than that of Codex standard level. One day after pesticide application, the levels of pesticides were decreased about 35 and 31% for ethion and imidacloprid, respectively, which still were higher than the MRL. Washing procedure led to about 51 and 42.5% loss in ethion and imidacloprid residues, respectively. Peeling procedure also led to highest loss of 93.4 and 63.7% in ethion and imidacloprid residues, respectively. The recovery for both target analytes was in the range between 88 and 102%. The residue values in collected samples one hour after pesticides application were higher than standard value. The storing, washing, and peeling procedures lead to the decrease of pesticide residues in greenhouse cucumbers. Among them, the peeling procedure has the greatest impact on residual reduction. Therefore, these procedures can be used as simple and effective processing techniques for reducing and removing pesticides from greenhouse products before their consumption.

  10. Residues of Organochlorinated Pesticides in Soil from Tomato ...

    African Journals Online (AJOL)

    This work presents the concentrations of five pesticide residues, lindane, chlorpyrifos, endosulfan, p, p'-DDE and p, p'-DDD in soil samples collected from tomato fields in Ngarenanyuki, Tanzania. Endosulfan sulphate was detected in 100 % of the sample analysed with mean concentration of 0.2407 mg/kg dw. Chlorpyrifos ...

  11. Determination of erythromycin and tylosin residues in honey by LC/MS/MS.

    Science.gov (United States)

    Granja, Rodrigo; Niño, Alfredo Montes; Zucchetti, Roberto; Niño, Rosario Montes; Patel, Raj; Salerno, Alessandro Gonzalez

    2009-01-01

    Antibiotics are used in apiculture to protect bees against a variety of brood diseases. As a result of the development of resistance to oxytetracycline, erythromycin and tylosin are increasingly used for the prevention and treatment of these diseases. Therefore, Brazilian authorities have added these antibiotics to the National Regulatory Monitoring Program for the control of residues in honey. An analytical method has been developed for the determination of residues of erythromycin and tylosin in honey. The procedure involves solid-phase extraction of diluted honey samples with Bond Elut cartridges, followed by LC/MS with electrospray positive ionization in the multiple reaction monitoring mode. Two characteristic transitions were monitored for both drugs. Average analyte recoveries of erythromycin and tylosin ranged from 99 to 109% from sets of replicate honey samples fortified with drug concentrations of 5, 10, 15, and 20 microg/kg. The method decision limits were determined to be 1.27 and 0.59 microg/kg for erythromycin and tylosin, respectively. The detection capabilities were 5 and 5.2 microg/kg for erythromycin and tylosin, respectively.

  12. Estudo da variação da concentração de metano no biogás produzido a partir das águas residuárias do café A study on the variation of methane concentration in biogas produced from coffee wastewater

    Directory of Open Access Journals (Sweden)

    Marco Antônio Calil Prado

    2010-04-01

    Full Text Available A água residuária do café (ARC, originada no processamento dos frutos do cafeeiro, produz quantidade considerável de biogás que pode e deve ser utilizado como fonte de energia alternativa e complementar. Neste trabalho, foi estudada a variação da concentração de metano do biogás produzido a partir das ARC, por tratamento anaeróbio, em reator UASB, em escala laboratorial. As amostras foram coletadas durante 86 dias. As análises da concentração de metano foram realizadas por cromatografia gás-sólido (CGS. A produção de biogás e de metano, foi de 0,545 a 0,602 m³ kg-1DQO removida e de 0,382 a 0,421 m³ kg-1 DQO removida, respectivamente. Os resultados da concentração de metano no biogás variaram de 48,60 a 68,14 %, influenciados pela variação dos parâmetros temperatura, pH, acidez e compostos fenólicos presentes nas ARC. Como havia sido previsto, as maiores concentrações de metano foram verificadas nos períodos em que o pH estava mais próximo da neutralidade.The wastewater produced from wet coffee processing (WCP, originated from the coffee fruits, can produce great quantities of biogas, which, in turn, can be also used as an alternative or complementary energy source. In this research, we studied the variation of methane concentration produced by WCP in a laboratory-scale UASB reactor with anaerobic treatment. The samples were collected during a period of 86 days. The methane concentration was measured through gas solid chromatography (GSC. The production of biogas and methane ranged from 0.545 to 0.602 m³ kg-1DQO removed and from 0.382 a 0.421 m³ kg-1 DQO removed, respectively. Methane presence in the biogas ranged from 48.60% to 68.14 %. This variation was influenced by the following parameters: temperature, pH, acidity, and phenol compounds present in the WCP. As expected, greater concentrations of methane gas were verified during the periods when the pH close to neutral.

  13. Pesticide residues in brain tissues of dairy cattle in Lembang

    Directory of Open Access Journals (Sweden)

    Indraningsih

    2006-03-01

    Full Text Available The use of pesticides to control plant diseases may cause residual formation in crops, its byproduct and environmental. Furthermore, the use of agriculture byproduct as animal feed may cause poisoning or residual formation in animal products. The purpose of this study is to investigate of pesticide residues in brain tissues of dairy cattle in relation to animal feed as a contamination source. Samples consisted of animal feeds (19 samples of fodder and 6 samples of feed, 31 samples of sera and 25 samples of brain tissues of dairy cattle collected from Lembang, West Java. Feeds and fodders were collected from dairy farms located in Lembang. Sera were directly collected from 31 heads of Frisien Holstein (FH cattle from the same location, while brain tissues of FH cattle were collected from a local animal slaughtering house. Pesticide residues were analysed using gas chromatography (GC. Both residues of organochlorines and organophosphates were detected from brain tissues with average residue concentration OP was 22.7 ppb and OC was 5.1 ppb and a total residue was 27.8 ppb. The pesticide residues in brain tissues are new information that should be taken into consideration since the Indonesian consumed this tissues as an oval. Although pesticides residue concentration was low, pathological changes were noted microscopically from the brain tissues including extracellular vacuolisation, focal necrosis, haemorrhages, dilatation of basement membrane without cellular infiltration. Both pesticide residues were also detected in sera, where OP (9.0 ppb was higher than OC (4.9 ppb. These pesticides were also detected in animal feeds consisting fodders and feeds. Residues of OP (12.0 ppb were higher than OC (1.8 ppb in feeds, but residues of OP (16.8 ppb were lower than OC (18.7 ppb in fodders. Although, pesticide residues in sera and brain tissues were below the maximum residue limits (MRL of fat, the presence of pesticides in brain tissues should be taken

  14. Regulatory framework for NORM residues in Belgium

    Energy Technology Data Exchange (ETDEWEB)

    Pepin, S.; Dehandschutter, B.; Poffijn, A.; Sonck, M. [Federal Agency for Nuclear Control (FANC), Rue Ravenstein 36, 1000 Brussels (Belgium)

    2013-07-01

    The Belgian radiation protection authority (Federal Agency for Nuclear Control - FANC) has published in March 2013 a decree regulating the acceptance of NORM residues by nonradioactive waste treatment facilities. This regulation is based on the concept of 'work activities involving natural radiation sources' in the sense of article 40 of the 96/29/EURATOM directive. The disposal or processing facilities which accept NORM residues with an activity concentration above a generic exemption level will be considered as 'work activities' and submitted to declaration according to the Belgian radiation protection regulations. On basis of this declaration, specific acceptance criteria for the different types of processing/ disposal of the residues (disposal on landfill, recycling into building materials, etc.) are imposed. FANC has drafted guidelines for these acceptance criteria. A methodological guide for the operators of the concerned facilities was also published. Moreover, sites where significant quantities of NORM residues are or have been disposed, are subjected to an environmental monitoring in the framework of the national program of radiological surveillance of FANC. FANC also introduced in its regulations the concept of anthropogenic radon-prone areas: e.g. former phosphogypsum stacks have been defined as anthropogenic radon-prone areas, which allows some form of regulatory control of these sites. (authors)

  15. Obtention of ceramic pigments with residue from electroplating

    International Nuclear Information System (INIS)

    Boss, A.; Kniess, C.T.; Aguiar, B.M. de; Prates, P.B.; Milanez, K.

    2011-01-01

    The incorporation of industrial residues in industrial processes opens up new business opportunities and reduces the volume of extraction of raw materials, preserving natural resources, which are limited. An important residue is the mud from galvanic industry, consisting of alkali and transition metals. According to NBR 10004/2004, this residue can be classified as Class I (hazardous), depending on the concentration of metals present in the mud. This paper proposes a method for reusing the residue from electroplating in ceramic pigments. The characterization of residual plating was obtained by chemical analysis, mineralogical analysis and pH measurements. The electroplating waste was incorporated in different percentages on a standard pigment formula of industrial ceramic, consisting mainly of Zn, Fe and Cr. The obtained pigments were applied in ceramic glazes to colorimetric and visual analysis, which showed good results with the addition of up to 15% of industrial waste. (author)

  16. Laboratory studies of the properties of in-situ burn residues: chemical composition of residues

    International Nuclear Information System (INIS)

    Trudel, B.K.; Buist, I.A.; Schatzke, D.; Aurand, D.

    1996-01-01

    The chemical composition of the residue from small-scale burns of thick oil slicks was studied. The objective was to describe the changes in chemical composition in oils burning on water and to determine how these changes were influenced by the condition of the burn. Small-scale test burns involved burning 40-cm diameter pools of oil on water. A range of eight oil types including seven crude oils and an automotive diesel were burned. For each oil, slicks of fresh oil of three different thicknesses were tested. Two of the oils were tested before and after weathering. Results showed that the composition of the residue differed greatly from the parent oil. Asphaltenes, high-boiling-point aromatics and resins remained concentrated in the burn residue. The burning of slicks appeared to remove most of the lower-molecular weight aromatic hydrocarbons which included the more toxic and more bioavailable components of the crude oils. 11 refs., 6 tabs

  17. Amiodarone Rifampicin Drug-Drug Interaction Management with Therapeutic Drug Monitoring.

    Science.gov (United States)

    Oude Munnink, Thijs H; Demmer, Anna; Slenter, Roel H J; Movig, Kris L L

    2018-02-20

    The authors present a case of a 69-year-old man with arrhythmogenic right ventricular cardiomyopathy controlled with amiodarone and an infected orthopedic prosthesis requiring treatment with rifampicin. This combination involves a pharmacokinetic drug-drug interaction leading to subtherapeutic drug concentrations of amiodarone and its active metabolite. The long half-life of amiodarone and its active metabolite in combination with the late onset and offset of cytochrome P4503A (CYP3A4) induction by rifampicin makes this a challenging drug-drug interaction to cope with in clinical practice. Before, during, and after rifampicin treatment, the serum concentrations of amiodarone and its active metabolite were measured and the amiodarone dose was adjusted accordingly. The amiodarone dose required to maintain effective concentrations was 450% of the initial dose. The drug-drug interaction between amiodarone and rifampicin is relevant, both clinically and pharmacokinetically, and can be managed by dose adjustments of amiodarone based on serum concentrations.

  18. Residual Neuromuscular Blockade in the Critical Care Setting.

    Science.gov (United States)

    Stawicki, Nicole; Gessner, Patty

    2018-01-01

    Residual neuromuscular blockade is a widespread challenge for providers in the acute care setting that, if left unrecognized or untreated, places patients at higher risk for morbidity and mortality. The condition is estimated to occur in 26% to 88% of patients undergoing general anesthesia. The role of the advanced practice nurse in the acute care setting is to facilitate a safe recovery process by identifying early signs of deterioration and supporting the patient until full muscular strength has returned. This article discusses the prevalence of residual neuromuscular blockade and associated complications and patient risk factors. A review is included of the current uses for neuromuscular blockade, pathophysiology of the neuromuscular junction, pharmacologic characteristics of neuromuscular blocking agents (including drug-drug interactions), monitoring modalities, and effectiveness of reversal agents. Treatment recommendations pertinent to residual neuromuscular blockade are outlined. ©2018 American Association of Critical-Care Nurses.

  19. Assessment Of Antibiotic Residues In Milk Collected At Tanga Dairy ...

    African Journals Online (AJOL)

    A study on drug residues content was done on milk received by Tanga Dairy Cooperative Union in Tanga municipality. Milk samples (384) were collected from 96 farmers on four consecutive days. Forty two of the sampled farmers were interviewed using a questionnaire. The Charm- Aim-96 test which detects permitted ...

  20. Antimicrobial residues screening in pigs and goats slaughtered in ...

    African Journals Online (AJOL)

    Ekene Vivienne Ezenduka

    2012-07-17

    Jul 17, 2012 ... 2001; Pavlov et al., 2008). Antimicrobial use in food animals may result to residues in their products (meat, milk and egg) especially when the stipulated withdrawal period of the agent is not observed. This use of antimicrobial drugs in food animals has recently become a very important public health issue ...

  1. Viscoelastic properties of microfibrillated cellulose (MFC) produced from agricultural residue corn stover

    Science.gov (United States)

    The rheological properties of microfibrillated cellulose (MFC) produced from agricultural residue corn stover were investigated. The corn stover MFC gels exhibited concentration-dependent viscoelastic properties. Higher corn stover MFC concentrations resulted in stronger viscoelastic properties. Th...

  2. Viscoelastic properties of microfibrillated cellulose (MFC) produced from agricultural residue corn stover

    Science.gov (United States)

    The rheological properties of microfibrillated cellulose (MFC) produced from agricultural residue corn stover were investigated. The corn stover MFC gels exhibited concentration-dependent viscoelastic solid properties. Higher corn stover MFC concentrations resulted in stronger viscoelastic propertie...

  3. Concentrating Radioactivity

    Science.gov (United States)

    Herrmann, Richard A.

    1974-01-01

    By concentrating radioactivity contained on luminous dials, a teacher can make a high reading source for classroom experiments on radiation. The preparation of the source and its uses are described. (DT)

  4. Marine Tar Residues: a Review

    OpenAIRE

    Warnock, April M.; Hagen, Scott C.; Passeri, Davina L.

    2015-01-01

    Marine tar residues originate from natural and anthropogenic oil releases into the ocean environment and are formed after liquid petroleum is transformed by weathering, sedimentation, and other processes. Tar balls, tar mats, and tar patties are common examples of marine tar residues and can range in size from millimeters in diameter (tar balls) to several meters in length and width (tar mats). These residues can remain in the ocean environment indefinitely, decomposing or becoming buried in ...

  5. Functional residual capacity measurement by heptafluoropropane in ventilated newborn lungs

    OpenAIRE

    Kusztrich, Ariane

    2012-01-01

    Objective: Heptafluoropropane is an inert gas commercially used as propellant for inhalers. Since heptafluoropropane can be detected in low concentrations, it could also be used as a tracer gas to measure functional residual capacity. The aim of the present study was to validate functional residual capacity measurements by heptafluoropropane wash-in/wash-out (0.8%) during mechanical ventilation in small, surfactant-depleted lungs using a newborn piglet model. Design: Prospective laborato...

  6. Residual stress effects in tubular K-joints crack growth

    OpenAIRE

    Acevedo, Claire; Nussbaumer, Alain

    2010-01-01

    Seeking light and transparent bridge designs, engineers and architects have found an efficient and artistic way to fulfill their requirements: steel tubular bridges. Like any other welded structure, the joints of this kind of bridge suffer from high tensile weld residual stresses. Combined with high stress concentrations, tensile residual stress is a relevant factor in fatigue crack development. Therefore, an experimental study has been carried out on tubular joints in order to characterize ...

  7. Effect of household and industrial processing on levels of pesticide residues and degradation products in melons

    OpenAIRE

    Bonnechère, Aurore; Hanot, Vincent; Bragard, Claude; Bedoret, Thomas; Van Loco, Joris

    2012-01-01

    Abstract Two varieties of melons (Cucumis melo) were treated by two fungicides (carbendazim and maneb) and four insecticides (acetamiprid, cyromazin, imazalil and thiamethoxam) to quantify the effect of household processing on the pesticide residues. To ensure sufficiently high levels of residues in flesh and peels, the most concentrated formulations were applied pursuant to Good Agricultural Practices (GAPs). The peeling step decreased the concentration of pesticide residues for ...

  8. A manual for implementing residual radioactive material guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Gilbert, T.L.; Yu, C.; Yuan, Y.C.; Zielen, A.J.; Jusko, M.J.; Wallo, A. III

    1989-06-01

    This manual presents information for implementing US Department of Energy (DOE) guidelines for residual radioactive material at sites identified by the Formerly Utilized Sites Remedial Action Program (FUSRAP) and the Surplus Facilities Management Program (SFMP). It describes the analysis and models used to derive site-specific guidelines for allowable residual concentrations of radionuclides in soil and the design and use of the RESRAD computer code for calculating guideline values. It also describes procedures for implementing DOE policy for reducing residual radioactivity to levels that are as low as reasonably achievable. 36 refs., 16 figs, 22 tabs.

  9. Washing effects of limonene on pesticide residues in green peppers.

    Science.gov (United States)

    Lu, Hai-Yan; Shen, Yan; Sun, Xing; Zhu, Hong; Liu, Xian-Jin

    2013-09-01

    The presence of pesticide residues in food has caused much concern. The low health risks and environmental impacts of limonene make it a very interesting solvent for use in green chemistry. Washing effects of limonene on pesticide residues of methyl chlorpyrifos, chlorothalonil, chlorpyrifos, fenpropathrin and deltamethrin were investigated in green pepper. Results showed that washing with a low concentration of limonene for 5 min (where LOQ is limit of quantitation) caused 53.67%, limonene for 10 min produced 55.90%, limonene for 5 min was the optimal treatment for elimination of pesticide residues in green pepper, considering effect and treatment time as well as cost. © 2013 Society of Chemical Industry.

  10. A manual for implementing residual radioactive material guidelines

    International Nuclear Information System (INIS)

    Gilbert, T.L.; Yu, C.; Yuan, Y.C.; Zielen, A.J.; Jusko, M.J.; Wallo, A. III; Argonne National Lab., IL; Dames and Moore, West Valley, NY; Argonne National Lab., IL; USDOE Assistant Secretary for Nuclear Energy, Washington, DC

    1989-06-01

    This manual presents information for implementing US Department of Energy (DOE) guidelines for residual radioactive material at sites identified by the Formerly Utilized Sites Remedial Action Program (FUSRAP) and the Surplus Facilities Management Program (SFMP). It describes the analysis and models used to derive site-specific guidelines for allowable residual concentrations of radionuclides in soil and the design and use of the RESRAD computer code for calculating guideline values. It also describes procedures for implementing DOE policy for reducing residual radioactivity to levels that are as low as reasonably achievable. 36 refs., 16 figs, 22 tabs

  11. Radioactivity of combustion residues from coal-fired power stations

    International Nuclear Information System (INIS)

    Vom Berg, W.; Puch, K.H.

    1996-01-01

    Each year in Germany, about 18 mill. t of combustion residues are produced from the combustion of bituminous coal and lignite. They are utilized to a great extent in the construction industry and in mining. During the combustion of coal, the radio-nuclides remain predominantly in the ash. The radionuclide concentration in lignite ash is within the range of that in natural soil. The combustion residues of bituminous coal contain radio-nuclides of a similar order of magnitude as also can occur in natural rock. The utilization of combustion residues in construction materials makes a negligible contribution to radiation exposure through retention in buildings. (orig.) [de

  12. The use of bisphosphonates for bone-specific drug delivery

    NARCIS (Netherlands)

    Farbod, K.

    2016-01-01

    The pharmacological efficacy of conventional drug formulations can be improved through the use of drug delivery systems. Controlled drug delivery systems are intended to deliver drugs locally at predetermined rates for predefined periods of time. By delivering pharmacologically high concentrations

  13. Depletion of tylosin residues in feathers, muscle and liver from broiler chickens after completion of antimicrobial therapy.

    Science.gov (United States)

    Cornejo, Javiera; Pokrant, Ekaterina; Carvallo, Carolina; Maddaleno, Aldo; San Martín, Betty

    2018-03-01

    Tylosin is one of the most commonly used antimicrobial drugs from the macrolide family and in broiler chickens it is used specially for the treatment of infectious pathologies. The poultry industry produces several by-products, among which feathers account for up to 7% of a chicken's live weight, thus they amount to a substantial mass across the whole industry. Feathers have been repurposed as an animal feed ingredient by making them feather meal. Therefore, the presence of high concentrations of residues from antimicrobial drugs in feathers might pose a risk to global public health, due to re-entry of these residues into the food chain. This work aimed to characterise the depletion behaviour of tylosin in feather samples, while considering its depletion in muscle and liver tissue samples as a reference point. To achieve this goal, we have implemented and validated an analytical methodology suitable for detecting and quantifying tylosin in these matrices. Sixty broiler chickens, raised under controlled conditions, received an oral dose of 32 mg kg -1 of tylosin for 5 days. Tylosin was quantified in muscle, liver and feathers by liquid chromatography coupled with a photodiode array detector (HPLC-DAD). High concentrations of tylosin were detected in feather samples over the whole experimental period after completing both the therapy and the recommended withdrawal time (WDT). On the other hand, tylosin concentrations in muscle and liver tissue samples fell below the limit of detection of this method on the first sampling day. Our results indicate that the WDT for feather samples is 27 days, hence using feather meal for the formulation of animal diets or for other agricultural purposes could contaminate with antimicrobial residues either other livestock species or the environment. In consequence, we recommend monitoring this matrix when birds have been treated with tylosin, within the context of poultry farming.

  14. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Sagnik, E-mail: Sagnik.Chatterjee@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Richert, Lysiane, E-mail: l.richert@kaly-cell.com [KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim (France); Augustijns, Patrick, E-mail: Patrick.Augustijns@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Annaert, Pieter, E-mail: Pieter.Annaert@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium)

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  15. Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

    International Nuclear Information System (INIS)

    Chatterjee, Sagnik; Richert, Lysiane; Augustijns, Patrick; Annaert, Pieter

    2014-01-01

    Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

  16. Radionuclides in Bayer process residues: previous analysis for radiological protection

    International Nuclear Information System (INIS)

    Cuccia, Valeria; Rocha, Zildete; Oliveira, Arno H. de

    2011-01-01

    Natural occurring radionuclides are present in many natural resources. Human activities may enhance concentrations of radionuclides and/or enhance potential of exposure to naturally occurring radioactive material (NORM). The industrial residues containing radionuclides have been receiving a considerable global attention, because of the large amounts of NORM containing wastes and the potential long term risks of long-lived radionuclides. Included in this global concern, this work focuses on the characterization of radioactivity in the main residues of Bayer process for alumina production: red mud and sand samples. Usually, the residues of Bayer process are named red mud, in their totality. However, in the industry where the samples were collected, there is an additional residues separation: sand and red mud. The analytical techniques used were gamma spectrometry (HPGe detector) and neutron activation analysis. The concentrations of radionuclides are higher in the red mud than in the sand. These solid residues present activities concentrations enhanced, when compared to bauxite. Further uses for the residues as building material must be more evaluated from the radiological point of view, due to its potential of radiological exposure enhancement, specially caused by radon emission. (author)

  17. Radionuclides in Bayer process residues: previous analysis for radiological protection

    Energy Technology Data Exchange (ETDEWEB)

    Cuccia, Valeria; Rocha, Zildete, E-mail: vc@cdtn.b, E-mail: rochaz@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Oliveira, Arno H. de, E-mail: heeren@nuclear.ufmg.b [Universidade Federal de Minas Gerais (DEN/UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear

    2011-07-01

    Natural occurring radionuclides are present in many natural resources. Human activities may enhance concentrations of radionuclides and/or enhance potential of exposure to naturally occurring radioactive material (NORM). The industrial residues containing radionuclides have been receiving a considerable global attention, because of the large amounts of NORM containing wastes and the potential long term risks of long-lived radionuclides. Included in this global concern, this work focuses on the characterization of radioactivity in the main residues of Bayer process for alumina production: red mud and sand samples. Usually, the residues of Bayer process are named red mud, in their totality. However, in the industry where the samples were collected, there is an additional residues separation: sand and red mud. The analytical techniques used were gamma spectrometry (HPGe detector) and neutron activation analysis. The concentrations of radionuclides are higher in the red mud than in the sand. These solid residues present activities concentrations enhanced, when compared to bauxite. Further uses for the residues as building material must be more evaluated from the radiological point of view, due to its potential of radiological exposure enhancement, specially caused by radon emission. (author)

  18. Drug Facts

    Medline Plus

    Full Text Available ... Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen Together The Link Between Drug Use and HIV/AIDS Treatment & Recovery Why Does a Person Need Treatment? Does Drug Treatment Work? What ... Institute on Drug Abuse (NIDA) is part of the National Institutes of Health (NIH) , the principal biomedical and behavioral research agency ...

  19. Evaluation of residue-residue contact predictions in CASP9

    KAUST Repository

    Monastyrskyy, Bohdan

    2011-01-01

    This work presents the results of the assessment of the intramolecular residue-residue contact predictions submitted to CASP9. The methodology for the assessment does not differ from that used in previous CASPs, with two basic evaluation measures being the precision in recognizing contacts and the difference between the distribution of distances in the subset of predicted contact pairs versus all pairs of residues in the structure. The emphasis is placed on the prediction of long-range contacts (i.e., contacts between residues separated by at least 24 residues along sequence) in target proteins that cannot be easily modeled by homology. Although there is considerable activity in the field, the current analysis reports no discernable progress since CASP8.

  20. An overview of the main foodstuff sample preparation technologies for tetracycline residue determination.

    Science.gov (United States)

    Pérez-Rodríguez, Michael; Pellerano, Roberto Gerardo; Pezza, Leonardo; Pezza, Helena Redigolo

    2018-05-15

    Tetracyclines are widely used for both the treatment and prevention of diseases in animals as well as for the promotion of rapid animal growth and weight gain. This practice may result in trace amounts of these drugs in products of animal origin, such as milk and eggs, posing serious risks to human health. The presence of tetracycline residues in foods can lead to the transmission of antibiotic-resistant pathogenic bacteria through the food chain. In order to ensure food safety and avoid exposure to these substances, national and international regulatory agencies have established tolerance levels for authorized veterinary drugs, including tetracycline antimicrobials. In view of that, numerous sensitive and specific methods have been developed for the quantification of these compounds in different food matrices. One will note, however, that the determination of trace residues in foods such as milk and eggs often requires extensive sample extraction and preparation prior to conducting instrumental analysis. Sample pretreatment is usually the most complicated step in the analytical process and covers both cleaning and pre-concentration. Optimal sample preparation can reduce analysis time and sources of error, enhance sensitivity, apart from enabling unequivocal identification, confirmation and quantification of target analytes. The development and implementation of more environmentally friendly analytical procedures, which involve the use of less hazardous solvents and smaller sample sizes compared to traditional methods, is a rapidly increasing trend in analytical chemistry. This review seeks to provide an updated overview of the main trends in sample preparation for the determination of tetracycline residues in foodstuffs. The applicability of several extraction and clean-up techniques employed in the analysis of foodstuffs, especially milk and egg samples, is also thoroughly discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Analysis of sulfonamides, tilmicosin and avermectins residues in typical animal matrices with multi-plug filtration cleanup by liquid chromatography-tandem mass spectrometry detection.

    Science.gov (United States)

    Qin, Yuhong; Jatamunua, Freedom; Zhang, Jingru; Li, Yanjie; Han, Yongtao; Zou, Nan; Shan, Jihao; Jiang, Yanbin; Pan, Canping

    2017-05-15

    The frequent use of various veterinary drugs could lead to residue bioaccumulation in animal tissues, which could cause dietary risks to human health. In order to quickly analyze the residues, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for detecting Sulfonamides, Tilmicosin and Avermectins (AVMs) residues in animal samples. For sample preparation, modified QuEChERS (quick, easy, cheap, effective, rugged and safe) and ultrasound-assisted extraction (UAE) methods were used. For sample cleanup, n-Hexane delipidation and multi-plug filtration cleanup (m-PFC) method based on primary-secondary amine (PSA) and octadecyl-silica (C18) were used, followed by LC-MS/MS analysis. It was validated on 7 animal matrices (bovine, caprine, swine meat and their kidneys, milk) at two fortified concentration levels of 5 and 100μg/kg. The recoveries ranged from 82 to 107% for all analytes with relative standard deviations (RSDs) less than 15%. Matrix-matched calibrations were performed with coefficients of determination above 0.998 for all analytes within concentration levels of 5-500μg/kg. The developed method was successfully used to analysis veterinary drugs of real animal samples from local markets. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Escherichia Coli-Lux Biosensor Used to Monitor the Cytotoxicity and Genotoxicity of Pharmacological Residues in Environment

    Directory of Open Access Journals (Sweden)

    Eliza Hawrylik

    2018-05-01

    Full Text Available The aim of the study was to evaluate the usefulness of Escherichia coli K-12 RFM 443 recA::lux for cytotoxicity and genotoxicity monitoring of metoprolol in the environment. Metoprolol is one of the most popular cardiac drug which belongs to the group of β–blockers. The drug was applied at concentrations ranging from 0.01 µg/cm3 to 100 µg/cm3. The conducted studies are preliminary studies aimed at validation of the recA::lux gene construct in the direction of determining its sensitivity to metoprolol. The drug concentrations were selected experimentally to obtain a positive luminescence response. Obtained data indicated the influence of metoprolol on lux gene expression and recA promoter activity based on the use of laboratory samples using PBS buffer. Results indicate a potential possibility of using a bacterial biosensor Escherichia coli K - 12 RFM 443 with recA::lux gene fusion in cytotoxicity and genotoxicity monitoring of the cardiac drugs residue in the environment.

  3. Detection of pencillin residue in cow milk at Kombolcha dairy farms ...

    African Journals Online (AJOL)

    The use of antibiotics in dairy cattle for the treatment of diseases such as mastitis has contributed to the presence of residues in dairy products. Penicillin is commonly used veterinary drug to treat mastitis in dairy cattle. However, abundant use of it may be associated with the presence of its residues in milk at unsafe ...

  4. Drug Facts

    Medline Plus

    Full Text Available ... Where Can Someone Find Treatment and Recovery Resources? Prevention Help Children and Teens Stay Drug-Free Talking ... You Used Drugs in the Past Drug Use Prevention Phone Numbers and Websites Search Share Listen English ...

  5. Hazardous Drugs

    Science.gov (United States)

    ... and hazardous drugs in the workplace. Pharmacy . OSHA Hospital eTool. Reviews safety and health topics related to hazardous drugs including drug handling, administration, storage, and disposal. OSHA has identified worker exposure ...

  6. Drug Facts

    Medline Plus

    Full Text Available ... Information About Drugs Alcohol Bath Salts Cocaine Heroin Marijuana MDMA Meth Pain Medicines Spice (K2) Tobacco/Nicotine Other Drugs You can call 1-800-662-HELP (4357) at any time to find drug treatment ...

  7. Drug Reactions

    Science.gov (United States)

    ... problem is interactions, which may occur between Two drugs, such as aspirin and blood thinners Drugs and food, such as statins and grapefruit Drugs and supplements, such as ginkgo and blood thinners ...

  8. Drug Facts

    Medline Plus

    Full Text Available ... symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What Makes Someone More Likely to Get Addicted to Drugs? Does Addiction Run in Families? Why Is It So Hard to ...

  9. Club Drugs

    Science.gov (United States)

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... regarding prevention and treatment of MDMA. ( September 2017 ) View all related publications Related NIDA Notes Articles Narrative ...

  10. Drug Facts

    Medline Plus

    Full Text Available ... Other Effects on the Body Drug Use Hurts Brains Drug Use and Mental Health Problems Often Happen ... to prescription drugs. The addiction slowly took over his life. I need different people around me. To ...

  11. Drug Facts

    Medline Plus

    Full Text Available ... Facts Tobacco and Nicotine Facts Other Drugs of Abuse What is Addiction? What are some signs and symptoms of someone with a drug use problem? How Does Drug Use Become an Addiction? What ...

  12. Drug Facts

    Medline Plus

    Full Text Available ... Does a Person Need Treatment? Does Drug Treatment Work? What Are the Treatment Options? What Is Recovery? ... I want my daughter to avoid drugs. "Debbie" has been drug-free for years. She wants her ...

  13. Graphic Three-Axes Presentation of Residual Gas Analyser Data

    Science.gov (United States)

    Johnson, Kenneth R.; Levi, Alejandro G.

    1996-01-01

    Residual gas analyzers (RGA) are commonly used to measure the composition of residual gases in thermal-vacuum test chambers. Measurements from RGAs are often used to identify and quantify outgassing contaminants from a test article during thermal-vacuum testing. RGA data is typically displayed as snapshots in time, showing instantaneous concentrations of ions from ionized residual gas molecules at different atomic masses. A method was devised by the authors to present RGA data in a three-axis format, plotting atomic mass unit (AMU), ion concentration as a function of AMU, and time, to provide a clear graphic visualization ot trends in gas concentration changes and to initiate a valuable analytical tool to interpret test article outgassing rates during thermal-vacuum testing.

  14. Landfilling of waste incineration residues

    DEFF Research Database (Denmark)

    Christensen, Thomas Højlund; Astrup, Thomas; Cai, Zuansi

    2002-01-01

    Residues from waste incineration are bottom ashes and air-pollution-control (APC) residues including fly ashes. The leaching of heavy metals and salts from the ashes is substantial and a wide spectrum of leaching tests and corresponding criteria have been introduced to regulate the landfilling...

  15. Dicofol residues in eggs and carcasses of captive American kestrels

    Science.gov (United States)

    Wiemeyer, Stanley N.; Clark, D.R.; Spann, J.W.; Belisle, A.A.; Bunck, C.M.

    2001-01-01

    American kestrels (Falco sparverius) were fed diets containing 0 (control), 1, 3, 10, and 30 ?g/g (wet wt) of Kelthane?. Residues of dicofol and its metabolites were then analyzed in the eggs and carcasses of females. Significant differences occurred among treatments for residues of both p,p'-dicofol and p,p'-dechlorodicofol (DCD) in both eggs and carcasses and for p,p'-dicholorbenzophenone (DCBP) in eggs. Residue concentrations increased with increasing treatment exposure. Residues of p,p'-dicofol, p,p'-DCD, and p,p'-DCBP in eggs were significantly correlated with eggshell quality parameters. Significant correlations also occurred among contaminants in eggs and for individual contaminants between eggs and carcasses. The lowest-observed-dietary-effect concentration for eggshell thinning was 3 ?g/g, whereas 1 ?g/g may be considered to be near a no-observable-adverse-effect concentration. Concentrations of dicofol in potential prey items and eggs of wild birds generally have been lower than dietary-effect concentrations or concentrations in tissues or eggs associated with eggshell thinning and reduced reproductive success.

  16. Monitoring of Benomyl Residue in Mushroom Marketed in Hamadan City

    Directory of Open Access Journals (Sweden)

    S. Abdi

    2015-07-01

    Full Text Available Introduction & Objective: Pesticide residues in environment and food have a negative impact on the health of living organisms. Therefore, this study was carried out for evaluation of benomyl residues in mushroom marketed in Hamadan city in 2014 using spectrophotometry. Materials & Methods: 10 specimens of mushroom were collected from greenhouses and market basket of Hamadan city. After preparation and processing the samples in the laboratory, be-nomyl residues in samples were determined using a spectrophotometric m