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Sample records for drug residues

  1. Safety assessment of drug residues

    SciTech Connect

    Jackson, B.A.

    1980-05-15

    The safety assessment of drug residues is part of the process for defining the conditions for the safe use of drugs in food-producing animals. The information needed to assess the safety of drug residues is provided by chemical and toxicity tests. Toxicity tests are conducted to identify the type of effect produced and to determine the exposure concentrations that would be expected not to produce the effect. These tests include acute, subacute, and chronic toxicity tests, as well as reproduction studies and other special tests. The results are used to find an acceptable daily intake for drug residues that can be used to set a tolerance.

  2. Codex committee on veterinary drug residues.

    PubMed

    Crawford, L; Kugler, E G

    1986-12-01

    There has been widespread international concern over residues of veterinary drugs in food. However, until recently, there was little international cooperation in trying to find solutions to the problem. Many nations have taken steps to control the increased use of veterinary drugs, but the rules governing their use vary widely from country to country. Sharing of scientific expertise and other resources between countries would markedly improve this situation. With the need for international cooperation mounting, concerned drug regulators from 20 countries met in 1982 and again in 1984 to discuss international use of veterinary drugs. The group repeatedly called for a Codex committee on veterinary drug residues. At its 1983 meeting in Rome the Codex Alimentarius Commission convened an Expert Consultation to consider the need for a new committee. That international group of experts strongly agreed that a standing committee under the sponsorship of the commission should be established. In July of 1985, the commission unanimously voted to establish a new Committee on Residues of Veterinary Drugs in Food. The United States was chosen as host country. The committee will work closely with several existing Codex committees, but it has a clear mandate of its own. Its responsibilities will include establishing a list of priority drugs for review, recommending maximum residue levels, developing codes of practice, and reviewing analytical methods used to control veterinary drug residues. This fall, a new Codex committee has met for the first time--the Codex Committee on Residues of Veterinary Drugs in Food.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Evaluation of certain veterinary drug residues in food.

    PubMed

    2012-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including comments on documents under elaboration for the Codex Committee on Residues of Veterinary Drugs in Foods (CCRVDF), information on registration/approval status of veterinary drugs, extrapolation of maximum residue limits (MRLs), dietary exposure assessment methodologies, the decision-tree approach to the evaluation of residues of veterinary drugs and guidance for JECFA experts. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two antimicrobial agents (amoxicillin, apramycin), four anthelminthics (derquantel, ivermectin, monepantel, triclabendazole) and two antimicrobial agents and production aids (monensin and narasin). Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs) and proposed MRLs. PMID:22953379

  4. Evaluation of certain veterinary drug residues in food.

    PubMed

    2002-01-01

    This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers risk assessment principles and presents the views of the Committee on the FAO/WHO Project to update principles and methods for the risk assessment of chemicals in food. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: three anthelminthic agents (doramectin, ivermectin and tiabendazole), seven antimicrobial agents (cefuroxime, dihydrostreptomycin and streptomycin, lincomycin, neomycin, oxytetracycline and thiamphenicol), four insecticides (cyhalothrin, cypermethrin and alpha-cypermethrin, and phoxim) and one production aid (melengestrol acetate). Annexed to the report is a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and Maximum Residue Limits and further information required. PMID:12592988

  5. Evaluation of certain veterinary drug residues in food.

    PubMed

    2003-01-01

    The first part of the report presents the views of the Committee on assessment of carcinogenic risk, quality of data, marker residues, and the Joint FAO/WHO Project to update the principles and methods for the risk assessment of chemicals in food. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two antimicrobial agents (neomycin and flumequine), an antiprotozoal agent (imidocarb), three insecticides (deltamethrin, dicyclanil, and trichlorfon) and one production aid (carbadox). Annexed to the report is a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and Maximum Residue Limits. Corrigenda to WHO Technical Report Series 911: Evaluation of certain veterinary drug residues in food, 2002, are also included. PMID:12970947

  6. Health concerns and management of select veterinary drug residues.

    PubMed

    Baynes, Ronald E; Dedonder, Keith; Kissell, Lindsey; Mzyk, Danielle; Marmulak, Tara; Smith, Geof; Tell, Lisa; Gehring, Ronette; Davis, Jennifer; Riviere, Jim E

    2016-02-01

    The aim of this manuscript is to review the potential adverse health effects in humans if exposed to residues of selected veterinary drugs used in food-producing animals. Our other objectives are to briefly inform the reader of why many of these drugs are or were approved for use in livestock production and how drug residues can be mitigated for these drugs. The selected drugs include several antimicrobials, beta agonists, and phenylbutazone. The antimicrobials continue to be of regulatory concern not only because of their acute adverse effects but also because their use as growth promoters have been linked to antimicrobial resistance. Furthermore, nitroimidazoles and arsenicals are no longer approved for use in food animals in most jurisdictions. In recent years, the risk assessment and risk management of beta agonists, have been the focus of national and international agencies and this manuscript attempts to review the pharmacology of these drugs and regulatory challenges. Several of the drugs selected for this review can cause noncancer effects (e.g., penicillins) and others are potential carcinogens (e.g., nitroimidazoles). This review also focuses on how regulatory and independent organizations manage the risk of these veterinary drugs based on data from human health risk assessments.

  7. 75 FR 45640 - Draft Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-03

    ... guidance for industry entitled ``Residual Drug in Transdermal and Related Drug Delivery Systems.'' This... Systems.'' This draft guidance provides recommendations to developers and manufacturers of TDDS, TMDS, and... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Residual Drug in...

  8. Kinetic modelling and residue depletion of drugs in eggs.

    PubMed

    Hekman, P; Schefferlie, G J

    2011-06-01

    1. A physiologically-based pharmacokinetic model was developed for the purpose of describing the relationship between plasma concentration of drugs and their deposition into eggs. 2. By incorporating the physiology of egg formation into the model, the transfer of drugs into the egg albumen and yolk could be described using rate constants. 3. The model was used to describe concentrations in albumen and yolk of sulphanilamide, sulphaquinoxaline and pyrimethamine as a function of time using datasets from the literature. 4. The model could be used as a tool to obtain an insight into those properties of a drug which are responsible for the amount of residue in eggs, and could help in the design of critical studies for determining withdrawal periods for eggs. PMID:21732884

  9. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES FOR RESIDUES OF NEW ANIMAL DRUGS IN FOOD General Provisions § 556.1 General considerations; tolerances...

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

    PubMed Central

    2010-01-01

    Background Veterinary drugs such as clenbuterol (CL) and sulfamethazine (SM2) are low molecular weight (<1000 Da) compounds, or haptens, that are difficult to develop immunoassays due to their low immunogenicity. In this study, we conjugated the drugs to ovalbumin to increase their immunogenicity for antiserum production in rabbits and developed a protein microarray immunoassay for detection of clenbuterol and sulfamethazine. The sensitivity of this approach was then compared to traditional ELISA technique. 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. PMID:20158905

  11. Review of United States requirements for residual moisture in drugs.

    PubMed

    Seligmann, E B

    1976-10-01

    Officially recognized procedures for residual moisture determinations on biological products are described. These include gravimetric at ambient temperature and thermogravimetric analysis at specified temperatures for specific products. The bases for selecting the optimum residual moisture for a new product are discussed and values established for currently licensed products are listed. Comparisons are made between the procedures and requirements for biological products and the water determinations specificed in U.S. Pharmacopeia XIX.

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-03

    ... HUMAN SERVICES Food and Drug Administration Draft Guidance for Industry on Residual Solvents in Animal... 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...

  13. Emergency slaughter of casualty cattle increases the prevalence of anthelmintic drug residues in muscle.

    PubMed

    Cooper, K M; Whyte, M; Danaher, M; Kennedy, D G

    2012-08-01

    The ProSafeBeef project studied the prevalence of residues of anthelmintic drugs used to control parasitic worms and fluke in beef cattle in Ireland. Injured (casualty) cattle may enter the human food chain under certain conditions, verified by an attending veterinarian and the livestock keeper. An analytical survey was conducted to determine if muscle from casualty cattle contained a higher prevalence of anthelmintic drug residues than healthy (full slaughter weight) cattle as a result of possible non-observance of complete drug withdrawal periods. A validated analytical method based on matrix solid-phase dispersive extraction (QuEChERS) and ultra-performance liquid chromatography-tandem mass spectrometry was used to quantify 37 anthelmintic drugs and metabolites in muscle (assay decision limits, CCα, 0.15-10.2 µg kg⁻¹). Of 199 control samples of beef purchased in Irish shops, 7% contained detectable anthelmintic drug residues but all were compliant with European Union Maximum Residue Limits (MRL). Of 305 muscle samples from injured cattle submitted to abattoirs in Northern Ireland, 17% contained detectable residues and 2% were non-compliant (containing either residues at concentrations above the MRL or residues of a compound unlicensed for use in cattle). Closantel and ivermectin were the most common residues, but a wider range of drugs was detected in muscle of casualty cattle than in retail beef. These data suggest that specific targeting of casualty cattle for testing for anthelmintic residues may be warranted in a manner similar to the targeted testing for antimicrobial compounds often applied in European National Residues Surveillance Schemes. PMID:22632575

  14. Regulatory problems caused by contamination, a frequently overlooked cause of veterinary drug residues.

    PubMed

    Kennedy, D G; Cannavan, A; McCracken, R J

    2000-06-16

    The occurrence of violative residues of veterinary medicines and other, unauthorised, drugs in food of animal origin is an issue of popular concern within the European Union. Violations can occur as a result of improper use of a licensed product or through the illegal use of an unlicensed substance. However, a "violative" analytical result does not necessarily mean that abuse has occurred. Contamination of animal feedingstuffs, environmental contamination and animal-to-animal transfer of drugs can also cause residue violations. This paper reviews these inadvertent causes of residues violations in food, and includes data generated using chromatographic and non-chromatographic methods of analysis.

  15. 21 CFR 530.24 - Procedure for announcing analytical methods for drug residue quantification.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Procedure for announcing analytical methods for...-Producing Animals § 530.24 Procedure for announcing analytical methods for drug residue quantification. (a) FDA may issue an order announcing a specific analytical method or methods for the quantification...

  16. Occurrence of sulfa drug residues in canadian pork liver.

    PubMed

    Neidert, E; Saschenbrecker, P W; Patterson, J R; Fesser, A

    1985-09-01

    Sulfonamide residues in the livers of wholesome carcasses of Canadian pork were monitored over the six year period ending March 31, 1985. The annual rate of violative residues decreased from 9.92% to 2.75% over the course of the six years. At present the incidence of violation in the livers is 2.35% and there is no significant difference within the various regions of Canada. This would result in a muscle violative rate of 0.8%.The only sulfonamide found at violative levels was sulfamethazine. All violative samples were within the range 0.11-4.00 ppm. Over the period of the survey the incidence of violations at all levels decreased. Violations at higher levels decreased most rapidly resulting in a continuous reduction of the mean level in violative samples.

  17. Drug residues in animal tissues and their regulatory significance--the Canadian point of view.

    PubMed

    Campbell, D J

    1978-09-01

    Today it is almost impossible to produce food of animal origin which is free from traces of drugs or chemicals. In Canada the problem of drug residues is controlled by a method of assessment of human safety which involves many factors. The toxicity of the drug in laboratory animals or, if possible, in man, is established and a no-effect dose is then estimated. These studies require oral administration of the drug and include acute, subacute, and teratogenicity studies. Depending on these results, chronic reproductive or carcinogenicity studies may be required before a no-effect dose can be estimated. Residue studies must encompass data on metabolism, pharmacokinetics, and depletion studies in edible tissues and for products such as milk and eggs. For veterinary drug residues, we must consider the target food animal with its particular metabolism, tissue disposition, and excretion patterns. The analytical method for residue detection must be acceptable and its sensitivity limits suitable for the drug and its major metabolites.

  18. 77 FR 3653 - Import Tolerances for Residues of Unapproved New Animal Drugs in Food

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-25

    ... the Federal Register of August 10, 2001 (66 FR 42167), the Agency published an advance notice of... would have the resources for residue testing. B. Current Process for Establishing New Animal Drug... resistant bacteria in or on the target animal and the potential impact on human health. C....

  19. Determination of anthelmintic drug residues in milk using UPLC-MS/MS with rapid polarity switching

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A new UPLC-MS/MS (ultra-performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added...

  20. Neonatal Adaptation Issues After Maternal Exposure to Prescription Drugs: Withdrawal Syndromes and Residual Pharmacological Effects.

    PubMed

    Convertino, Irma; Sansone, Alice Capogrosso; Marino, Alessandra; Galiulo, Maria T; Mantarro, Stefania; Antonioli, Luca; Fornai, Matteo; Blandizzi, Corrado; Tuccori, Marco

    2016-10-01

    Exposure to drugs during pregnancy has the potential to harm offspring. Teratogenic effects are the most feared adverse outcomes in newborns; however, a wide spectrum of less known, usually reversible and often acute, neonatal adverse events can also occur due to drug intake by mothers during pregnancy, particularly in close proximity to delivery. This narrative review is aimed at the description of drugs and drug classes for which licit maternal use in the predelivery period has been associated with neonatal non-teratogenic disorders. For each drug class, epidemiology, clinical features, biological mechanism and management of these adverse reactions have been discussed in detail. Although these adverse reactions have been described mainly for substances used illicitly for recreational purposes, several prescription drugs have also been involved; these include mainly psychotropic medications such as opioids, antidepressants, antiepileptics and antipsychotics. These effects can be partly explained by withdrawal syndromes (defined also as 'neonatal abstinence syndrome') caused by the delivery-related discontinuation of the drug disposition from the mother to the fetus, with symptoms that may include feeding disorders, tremors, irritability, hypotonia/hypertonia, vomiting and persistent crying, occurring a few hours to 1 month after delivery. Otherwise, neonatal neurological and behavioral effects can also be caused by a residual pharmacological effect due to an accumulation of the drug in the blood and tissues of the newborn, with various symptoms related to the toxic effects of the specific drug class, usually developing a few hours after birth. With few exceptions, validated protocols for the assessment and management of withdrawal or residual pharmacological effects of these drugs in neonates are often lacking or incomplete. Spontaneous reporting of these adverse reactions seems limited, although it might represent a useful tool for improving our knowledge about

  1. The effect of cooking on veterinary drug residues in food: nicarbazin (dinitrocarbanilide component).

    PubMed

    Tarbin, J A; Bygrave, J; Bigwood, T; Hardy, D; Rose, M; Sharman, M

    2005-11-01

    The change of concentration of residues of the marker compound for the anti-coccidial drug nicarbazin, N,N'-bis(4-nitrophenyl)urea (dinitrocarbanilide, DNC), was investigated in model oil and aqueous solutions and in chicken muscle and egg. In model aqueous solutions, DNC decreased rapidly in concentration upon heating followed by a much more gradual decomposition. The curves produced when this information was plotted were not typical of exponential decay. In model cooking oil solutions, DNC generally showed a slower decrease in concentration over time when compared with aqueous solutions. DNC residues in egg were stable to microwave cooking and residues in chicken muscle were stable to stewing and microwaving. Other cooking procedures led to a decrease in amount of DNC by 22% to 48% of the total amount of analyte present. Only a small amount (<2%) of residue leached with juices which exuded as the food was cooked.

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

    PubMed Central

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

    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. PMID:27433102

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

    PubMed

    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. PMID:27433102

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

    PubMed

    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.

  5. Quantification of residual solvents in antibody drug conjugates using gas chromatography.

    PubMed

    Medley, Colin D; Kay, Jacob; Li, Yi; Gruenhagen, Jason; Yehl, Peter; Chetwyn, Nik P

    2014-11-19

    The detection and quantification of residual solvents present in clinical and commercial pharmaceutical products is necessary from both patient safety and regulatory perspectives. Head-space gas chromatography is routinely used for quantitation of residual solvents for small molecule APIs produced through synthetic processes; however residual solvent analysis is generally not needed for protein based pharmaceuticals produced through cultured cell lines where solvents are not introduced. In contrast, antibody drug conjugates and other protein conjugates where a drug or other molecule is covalently bound to a protein typically use solvents such as N,N-dimethylacetamide (DMA), N,N‑dimethylformamide (DMF), dimethyl sulfoxide (DMSO), or propylene glycol (PG) to dissolve the hydrophobic small molecule drug for conjugation to the protein. The levels of the solvent remaining following the conjugation step are therefore important to patient safety as these parental drug products are introduced directly into the patients bloodstream. We have developed a rapid sample preparation followed by a gas chromatography separation for the detection and quantification of several solvents typically used in these conjugation reactions. This generic method has been validated and can be easily implemented for use in quality control testing for clinical or commercial bioconjugated products.

  6. Tools to evaluate pharmacokinetics data for establishing maximum residue limits for approved veterinary drugs: examples from JECFA's work.

    PubMed

    Sanders, P; Henri, J; Laurentie, M

    2016-05-01

    Maximum residue limits (MRLs) for residues of veterinary drugs are the maximum concentrations of residues permitted in or on a food by national or regional legislation. In the process of MRLs recommendations by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), analysis of pharmacokinetic data describing the ADME process (absorption, distribution, metabolism and excretion) is a crucial step and requires the use of different pharmacokinetic tools. The results of animal metabolism studies are the prime determinants of the residue definition in food commodities. Substances labelled with radioactive isotopes are used so that the disposition of the residue can be followed as total residue and main metabolites concentrations. Residue depletion studies with radiolabelled parent drug will lead to the estimate of the time course of the total residue and to determine a marker residue. Depletion studies with an unlabelled drug provide more information on the time course of the marker residue in raw commodities after administration under approved practical conditions of use. By use of this information and after conversion with the total/residue marker ratio, MRLs are derived by comparison of the acceptable daily intake with the daily intakes calculated with different scenarios of dietary exposure. Progress in pharmacokinetic model such as physiologically based pharmacokinetics and population pharmacokinetics will drive the future research in this field to improved veterinary drug development. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27443212

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

    PubMed

    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.

  8. Multicomponent mesofluidic system for the detection of veterinary drug residues based on competitive immunoassay.

    PubMed

    Hu, Lei; Zuo, Peng; Ye, Bang-Ce

    2010-10-01

    An automated multicomponent mesofluidic system (MCMS) based on biorecognitions carried out on meso-scale glass beads in polydimethylsiloxane (PDMS) channels was developed. The constructed MCMS consisted of five modules: a bead introduction module, a bioreaction module, a solution handling module, a liquid driving module, and a signal collection module. The integration of these modules enables the assay to be automated and reduces it to a one-step protocol. The MCMS has successfully been applied toward the detection of veterinary drug residues in animal-derived foods. The drug antigen-coated beads (varphi250 microm) were arrayed in the PDMS channels (varphi300 microm). The competitive immunoassay was then carried out on the surface of the glass beads. After washing, the Cy3-labeled secondary antibody was introduced to probe the antigen-antibody complex anchored to the beads. The fluorescence intensity of each bead was measured and used to determine the residual drug concentration. The MCMS is highly sensitive, with its detection limits ranging from 0.02 (salbutamol) to 3.5 microg/L (sulfamethazine), and has a short assay time of 45 min or less. The experimental results demonstrate that the MCMS proves to be an economic, efficient, and sensitive platform for multicomponent detection of compound residues for contamination in foods or the environment.

  9. Effective management tools for participants at Codex Committee on Residues of Veterinary Drugs meetings.

    PubMed

    Kay, Jack F

    2016-05-01

    The Codex Committee on Residues of Veterinary Drugs in Food (CCRVDF) fulfils a number of functions revolving around standard setting. The core activities of the CCRVDF include agreeing priorities for assessing veterinary drug residues, recommending maximum residue limits for veterinary drugs in foods of animal origin, considering methods of sampling and analyses, and developing codes of practice. Draft standards are developed and progress through an agreed series of steps common to all Codex Alimentarius Commission Committees. Meetings of the CCRVDF are held at approximately 18-month intervals. To ensure effective progress is made with meetings at this frequency, the CCRVDF makes use of a number of management tools. These include circular letters to interested parties, physical and electronic drafting groups between plenary sessions, meetings of interested parties immediately prior to sessions, as well as break out groups within sessions and detailed discussions within the CCRVDF plenary sessions. A range of these approaches is required to assist advances within the standards setting process and can be applied to other Codex areas and international standard setting more generally. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27443198

  10. Veterinary drug residues in meat: Concerns and rapid methods for detection.

    PubMed

    Reig, Milagro; Toldrá, Fidel

    2008-01-01

    The use of substances having hormonal or thyreostatic action as well as β-agonists is banned in the European Union. 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 European consumers. The control of the absence of these forbidden substances in animal foods and feeds is regulated in the European Union by Directive96/23/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. A crucial step is the screening of veterinary drug residues in live animals, feeds and animal products in view of the remarkable number of samples and large variety of residues to be analysed. In recent years, different rapid methods having easy performance, high sensitivity and high throughput have been proposed and are being extensively used. These methods as well as other new methods are reviewed in this manuscript.

  11. [Do pharmaceutical waste and drug residue pose a risk to public health?].

    PubMed

    Haguenoer, Jean-Marie

    2010-01-01

    Recently, awareness has developed of the environmental consequences of drug waste and disposal. These residues are identified as coming from either diffuse sources, the most significant of which is via the discharge of these residues in urine and feces, and thus the sewage system and water contains these drug remnants and their metabolites, or from point sources, sometimes with very high levels of concentration in waste from chemical and pharmaceutical industries, health care settings, but also from intensive livestock farming and aquaculture. Depending on their physical chemistry properties, these substances are more or less naturally biodegradable and easily treated in sewage purification plants. The effectiveness of these treatment processes is highly random and unpredictable, but is overall around 60%, nevertheless with variations of 2-99% according to the molecules. The silt from these treatment plants, sometimes very rich in lipophilic substances is on occasion reused for agricultural application as fertilizer, paving the way for a possible contamination of crops. Furthermore, the use of veterinary drugs in animals can lead to soil contamination either directly or through manure and slurry. The contamination can equally reach and affect surface water, groundwater and sometimes the water intended for human consumption. The National academy of Pharmacy has established some general recommendations on the proper use of drugs, environmental monitoring and surveillance, risk assessment for humans and the environment, prevention and the need for prevention. Several categories of drugs are more worrying: cancer treatments, antibiotics as well as transfers of anti-bio-resistance, and hormonal derivatives which has been previously demonstrated to contribute, along with other molecules, to detrimental effects on endocrines.

  12. The effect of cooking on veterinary drug residues in food: 1. Clenbuterol.

    PubMed

    Rose, M D; Shearer, G; Farrington, W H

    1995-01-01

    The heat stability of clenbuterol was investigated. The drug was shown to be stable in boiling water at 100 degrees C. In cooking oil at 260 degrees C, losses were observed, indicating a half-life of about 5 min. The effect of a range of cooking processes (boiling, roasting, frying, microwaving) on clenbuterol residues in fortified and incurred tissue was studied. No net change in the amount of clenbuterol was observed in any of the cooking processes investigated except for deep frying using extreme conditions. There was little observed migration from the tissue into the surrounding liquid or meat juices. Clenbuterol residues were found not to be evenly distributed in the incurred raw tissue used for the investigation. The findings of this investigation show that data obtained from measurements on raw tissue are applicable for use in consumer exposure estimates and dietary intake calculations.

  13. Protonation of a Glutamate Residue Modulates the Dynamics of the Drug Transporter EmrE

    PubMed Central

    Gayen, Anindita; Leninger, Maureen; Traaseth, Nathaniel J.

    2015-01-01

    Secondary active transport proteins play a central role in conferring bacterial multidrug resistance. In this work, we investigated the proton-coupled transport mechanism for the Escherichia coli drug efflux pump EmrE using nuclear magnetic resonance (NMR) spectroscopy. Our results show that the global conformational motions necessary for transport are modulated in an allosteric fashion by the protonation state of a membrane-embedded glutamate residue. These observations directly correlate with the resistance phenotype for EmrE and the E14D mutant as a function of pH. Furthermore, our results support a model in which the pH gradient across the inner membrane of E. coli may be used on a mechanistic level to shift the equilibrium of the transporter in favor of an inward-open resting conformation poised for drug binding. PMID:26751516

  14. EU sampling strategies for the detection of veterinary drug residues in aquaculture species: are they working?

    PubMed

    Morris, D J; Gray, A J; Kay, J F; Gettinby, G

    2012-08-01

    Over the past 50 years, the culture of aquatic species in controlled conditions to enhance production has grown in importance and now provides nearly 50% of the world's seafood supply. In part, this expansion has been made possible by the use of antibiotics, antifungals, and other veterinary medicines to control disease and improve welfare. Despite guidelines being available, the sampling programmes for drug residue surveillance of aquaculture products recommended by the CODEX Alimentarius Commission were withdrawn in 2008 and put under review. Directive 96/23/EC sets out legislation to govern how sampling programmes for drug residue surveillance should be conducted within the EU. This directive applies both to produce raised within the EU and also imported products from third countries. This communication examines the existing EU sampling regimen for aquaculture products and comments on its possible application in a global context. We examine UK statutory sampling data that, while indicating the effectiveness of the directive, also suggests that the directive may lead to unnecessary sampling. Regarding imports, examination of the Rapid Alert System for Food and Feed (RASFF) database using process control charts and statistical modelling suggests that the sampling regimen described in the directive is effective but not sufficiently flexible for the range of aquaculture practices that exist. Limitations of the directive, datasets, and practices are further discussed.

  15. EU sampling strategies for the detection of veterinary drug residues in aquaculture species: are they working?

    PubMed

    Morris, D J; Gray, A J; Kay, J F; Gettinby, G

    2012-08-01

    Over the past 50 years, the culture of aquatic species in controlled conditions to enhance production has grown in importance and now provides nearly 50% of the world's seafood supply. In part, this expansion has been made possible by the use of antibiotics, antifungals, and other veterinary medicines to control disease and improve welfare. Despite guidelines being available, the sampling programmes for drug residue surveillance of aquaculture products recommended by the CODEX Alimentarius Commission were withdrawn in 2008 and put under review. Directive 96/23/EC sets out legislation to govern how sampling programmes for drug residue surveillance should be conducted within the EU. This directive applies both to produce raised within the EU and also imported products from third countries. This communication examines the existing EU sampling regimen for aquaculture products and comments on its possible application in a global context. We examine UK statutory sampling data that, while indicating the effectiveness of the directive, also suggests that the directive may lead to unnecessary sampling. Regarding imports, examination of the Rapid Alert System for Food and Feed (RASFF) database using process control charts and statistical modelling suggests that the sampling regimen described in the directive is effective but not sufficiently flexible for the range of aquaculture practices that exist. Limitations of the directive, datasets, and practices are further discussed. PMID:22851354

  16. Dielectric properties of residual water in amorphous lyophilized mixtures of sugar and drug

    NASA Astrophysics Data System (ADS)

    El Moznine, R.; Smith, G.; Polygalov, E.; Suherman, P. M.; Broadhead, J.

    2003-02-01

    Dielectric relaxation spectroscopy was used to investigate the properties of residual water in lyophilized formulations of a proprietary tri-phosphate drug containing a sugar (trehalose, lactose or sucrose) or dextran. The dielectric properties of each formulation were determined in the frequency range (0.1 Hz-0.1 MHz) and temperature range (30°C-Tg). The temperature dependence of the relaxation times for all samples showed Arrhenuis behaviour, from which the activation energy was derived. Proton hopping through the hydrogen-bonded network (clusters) of water molecules was suggested as the principle mode of charge transport. Significant differences in dielectric relaxation kinetics and activation energy were observed for the different formulations, which were found to correlate with the amount of monophosphate degradation product.

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

    NASA Astrophysics Data System (ADS)

    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).

  18. The effect of cooking on veterinary drug residues in food: 4. Oxytetracycline.

    PubMed

    Rose, M D; Bygrave, J; Farrington, W H; Shearer, G

    1996-04-01

    The heat stability of oxytetracycline (OTC) in water and vegetable oil was investigated. Results showed that the drug was unstable in water at 100 degrees C with a half-life of about 2 min, but more stable in oil at 180 degrees C where the half-life was about 8 min. The effect of a range of cooking processes including microwaving, boiling, roasting, grilling, braising and frying on OTC residues in incurred animal tissues was investigated. Substantial net reductions in OTC of 35-94% were observed, with temperature during cooking having the largest impact on the loss. Migration from the tissue into the surrounding liquid or meat juices was observed during the cooking processes. Diode-array analysis of heat-treated OTC standard solutions indicated that no individual closely related compound such as 4-epioxytetracycline, alpha- or beta-apooxytetracycline formed a significant proportion of the breakdown products. OTC was not evenly distributed throughout the tissue, but the effects of this were minimized by selecting adjacent samples for cooking and for the raw control. The findings of this investigation showed that the effect of cooking on residues of OTC should be considered before data obtained from measurements on raw tissue are used for consumer exposure estimates and dietary intake calculations.

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

    PubMed

    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.

  20. Small-world networks of residue interactions in the Abl kinase complexes with cancer drugs: topology of allosteric communication pathways can determine drug resistance effects.

    PubMed

    Tse, A; Verkhivker, G M

    2015-07-01

    The human protein kinases play a fundamental regulatory role in orchestrating functional processes in complex cellular networks. Understanding how conformational equilibrium between functional kinase states can be modulated by ligand binding or mutations is critical for quantifying molecular basis of allosteric regulation and drug resistance. In this work, molecular dynamics simulations of the Abl kinase complexes with cancer drugs (Imatinib and Dasatinib) were combined with structure-based network modeling to characterize dynamics of the residue interaction networks in these systems. The results have demonstrated that structural architecture of kinase complexes can produce a small-world topology of the interaction networks. Our data have indicated that specific Imatinib binding to a small number of highly connected residues could lead to network-bridging effects and allow for efficient allosteric communication, which is mediated by a dominant pathway sensitive to the unphosphorylated Abl state. In contrast, Dasatinib binding to the active kinase form may activate a broader ensemble of allosteric pathways that are less dependent on the phosphorylation status of Abl and provide a better balance between the efficiency and resilience of signaling routes. Our results have unveiled how differences in the residue interaction networks and allosteric communications of the Abl kinase complexes can be directly related to drug resistance effects. This study offers a plausible perspective on how efficiency and robustness of the residue interaction networks and allosteric pathways in kinase structures may be associated with protein responses to drug binding.

  1. Genotoxical, teratological and biochemical effects of anthelmintic drug oxfendazole Maximum Residue Limit (MRL) in male and female mice.

    PubMed

    El-Makawy, Aida; Radwan, Hasnaa A; Ghaly, Inas S; El-Raouf, A Abd

    2006-01-01

    Oxfendazole, methyl-5 (6)-phenylsulfinyl-2-benzimidazole carbamate, is a member of the benzimidazole family of anthelmintics. Anthelmintic benzimidazoles are widely used in meat producing animals (cattle, sheep and pigs) for control of endoparasites. The extensive use of veterinary drugs in food-producing animals can cause the presence of small quantities of the drug residues in food. Maximum residue limit or "MRL" means the maximum concentration of residue resulting from the use of a veterinary medicinal product which may be legally permitted recognized as acceptable in food. The FAO/WHO Expert Committee on Food Additives (1999) evaluations of toxicological and residue data, reported that oxfendazole (MRL) has toxicological hazards on human health. The toxicity of oxfendazole (MRL) was tested in male and female mice and their fetuses. Chromosomal aberrations, teratological examination and biochemical analysis were the parameters used in this study. The results show that oxfendazole MRL induced a mutagenic effect in all tested cell types. Also, oxfendazole exhibit embryotoxicity including teratogenicity. The biochemical results show that oxfendazole induced a disturbance in the different biochemical contents of all tested tissues. So, we must increase the attention paid to the potential risk of oxfendazole residues in human beings and should stress the need for careful control to ensure adherence to the prescribed withdrawal time of this drug.

  2. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... drug, has been shown to induce cancer in man or animal; however, such drug will not adversely affect... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES...

  3. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... drug, has been shown to induce cancer in man or animal; however, such drug will not adversely affect... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES...

  4. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... drug, has been shown to induce cancer in man or animal; however, such drug will not adversely affect... new animal drugs in food. 556.1 Section 556.1 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS TOLERANCES...

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

    PubMed

    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. PMID:27566339

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

    PubMed

    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.

  7. Occurrence of residues of the veterinary drug malachite green in eels caught downstream from municipal sewage treatment plants.

    PubMed

    Schuetze, Andrea; Heberer, Thomas; Juergensen, Susanne

    2008-08-01

    Residues of malachite green (MG), a veterinary drug illegally used for the treatment of aquacultured fish, have been found in wild eels caught from surface waters downstream from the sewers of different municipal sewage treatment plants (STPs). MG and its metabolite leucomalachite green (LMG) were detected with total concentrations up to 0.765 microg kg(-1) fresh weight in the tissues of 25 out of 45 eels caught from different lakes, a river and a canal in Berlin, Germany. In all cases, the occurrence of the residues could directly be linked to the presence of discharges by municipal STPs into the receiving surface waters. MG is a multiple-use compound that is also used to color materials. Thus, it appears to be reasonable that the residues of MG found in the eel samples originate from such uses, e.g. by wash off from clothes or paper towels colored with MG. Additional loads from legal uses of MG as veterinary drug for the treatment of ornamental fish (private aquaria) are possible. The results obtained from this study are the first proof of background contaminations of a veterinary drug found in samples of fish not intentionally treated with such agents. MG and LMG are regarded as potential genotoxic carcinogens making it impossible to establish a tolerable daily intake. A margin of exposure (MOE) approach was applied to evaluate the human health risk associated with the consumption of the eels investigated in this study. With a MOE of 3.4 million the chronic risk was classified as being very low. Nevertheless, due to their potential to act as genotoxic carcinogens, any oral exposure to residues of MG and LMG should be avoided. According to European Union law, zero tolerance applies to all residues of MG and LMG found in food for human consumption as MG is not registered for use as veterinary drug. PMID:18602134

  8. Residual Host Cell Protein Promotes Polysorbate 20 Degradation in a Sulfatase Drug Product Leading to Free Fatty Acid Particles.

    PubMed

    Dixit, Nitin; Salamat-Miller, Nazila; Salinas, Paul A; Taylor, Katherine D; Basu, Sujit K

    2016-05-01

    This study investigated the root cause behind an observed free fatty acid particle formation and resulting Polysorbate 20 (PS20) loss for a sulfatase drug product upon long-term storage at 5 ± 3°C. Reversed- phase chromatography with mass spectrometric analysis as well as charged aerosol detection was used to characterize the peaks associated with the intact and degraded PS20. Additionally, a proteomics study was undertaken to identify the residual host cell proteins in the sulfatase drug substance. PS20 stability studies were conducted in the presence of sulfatase, a sulfatase inhibitor, putative phospholipase B-like 2, and mock drug substance produced using a null cell line vector under experimental conditions optimized for PS20 degradation. This study provides the first published evidence where the residual host cell protein present in the drug substance was identified and experimentally shown to catalyze the breakdown of PS20 in a protein formulation over time, resulting in free fatty acid particles and PS20 loss. This study demonstrates the importance of early detection of potential impurities in the protein drug substance that may contribute to polysorbate degradation to make a judicious selection of the surfactant and its optimized concentration for the final drug product. PMID:27032893

  9. GLP principles and their role in supporting pharmacokinetic and residue depletion studies for drug registration and licensing.

    PubMed

    Croubels, Siska; De Backer, Patrick; Devreese, Mathias

    2016-05-01

    Good Laboratory Practice (GLP) is a quality system concerned with the organizational process and the conditions under which non-clinical health and environmental safety studies are planned, performed, monitored, recorded, archived, and reported. This paper focuses on the GLP principles applicable for veterinary drug registration and licensing purposes. First, a general overview of the GLP requirements is given, followed by a more specific comparison and discussion of the analytical method validation parameters and acceptance criteria of different international guidelines applied in the context of veterinary drug pharmacokinetic and residue depletion studies. Finally, some needs with respect to method validation and new developments in pharmacokinetic and residue depletion studies are highlighted. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27443213

  10. Distribution of phthalates, pesticides and drug residues in the dissolved, particulate and sedimentary phases from transboundary rivers (France-Belgium).

    PubMed

    Net, Sopheak; Rabodonirina, Suzanah; Sghaier, Rafika Ben; Dumoulin, David; Chbib, Chaza; Tlili, Ines; Ouddane, Baghdad

    2015-07-15

    Various drug residues, pesticides and phthalates are ubiquitous in the environment. Their presence in the environment has attracted considerable attention due to their potential impacts on ecosystem functioning and on public health. In this work, 14 drug residues, 24 pesticides and 6 phthalates have been quantified in three matrices (in the dissolved phase, associated to suspended solid matter (SSM), and in sediment) collected from fifteen watercourses and rivers located in a highly industrialized zone at the cross-border area of Northern France and Belgium. The extractions have been carried out using accelerated solvent extraction (ASE) for solid matrices (SSM and sediment) and using solid phase extraction (SPE) for liquid matrix. The final extract was analyzed using GC-MS technique. Among the three classes of compounds, phthalates have been found at highest level compared to pesticides and drug residues. The Σ6PAE concentrations were ranging from 17.2±2.58 to 179.1±26.9μgL(-1) in dissolved phase, from 2.9±0.4 to 21.1±3.2μgL(-1) in SSM and from 1.1±0.2 to 11.9±1.8μgg(-1)dw in sediment. The Σ14drug residue concentrations were lower than 1.3μgL(-1) in the dissolved phases, lower than 30ngL(-1) associated to SSM and from nondetectable levels to 60.7±9.1ngg(-1)dw in sediment. For pesticides, all compounds were below the LOQ values in dissolved phase and in sediment, and only EPTC could be quantified in SSM.

  11. Evaluation of certain veterinary drug residues in food. Sixty-second report of the Joint FAO/WHO Expert Committee on food additives.

    PubMed

    2004-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers conclusions on specific toxicological end-points, lipid-soluble residues of veterinary drugs with MRLs in milk, statistical methods for the estimation of MRLs, and the Committee's review and comments on documents provided by Codex Committees. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: five antibacterial agents (cefuroxime, chloramphenicol, flumequine, lincomycin, pirlimycin), four insecticides (cyhalothrin, cypermethrin and alpha-cypermethrin, doramectin, phoxim), and two production aids (melengestrol acetate, ractopamine). The Committee's comments on chloramphenicol found at low levels in animal products are also summarized. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes and proposed maximum residue limits. PMID:15587045

  12. Analytical method for simultaneous determination of pesticide and veterinary drug residues in milk by CE-MS.

    PubMed

    Blasco, Cristina; Picó, Yolanda; Andreu, Vicente

    2009-05-01

    This study reports a method based on CE-MS/MS detection developed for the multiresidue determination of seven pesticides (amidosulfuron, cyprodinil, cyromazine, imazaquin, pirimicarb, demethyl pirimicarb, procymidone) and eight residues of veterinary drugs (ciprofloxacin, enrofloxacin, sulfacetamide, sulfabenzamide, sulfachlorpyridazine, sulfaquinoxaline, sulfathiazole, sulfisoxazole), whose contents are regulated by the EU Council Regulations no. 396/2005 and no. 2377/90, in animal edible tissues. Milk samples were extracted with ACN and the extract was cleaned up using an Oasis hydrophilic-lipophilic balance SPE cartridge. The proposed method was validated in accordance with the European Commission Decision 657/2002. MS/MS experiments, using an IT analyzer, operating in multiple reaction monitoring mode, were carried out to achieve the minimum number of required identification points. Recovery data were also satisfactory, with values higher than 78% for most pesticides and veterinary drugs extracted from milk spiked at half the maximum residue limit established for the studied compounds. The RSD% (n = 5) were lower than 13 and 15% for intra-day and inter-day assays, respectively. The method was applied to establish the occurrence of the studied pesticides in 100 milk samples, attaining the determination of pesticide and veterinary drug residues in milk in the low microg/kg range. PMID:19384986

  13. Evaluation of certain veterinary drug residues in food. Forty-third report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    1995-01-01

    This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in foods. The first part of the report considers the evaluation of veterinary drugs with a long history of use and the implications of veterinary drug use in aquaculture, and discusses the need for adequate data. A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: a beta-adrenoceptor-blocking agent (carazolol), seven antimicrobial agents (dihydrostreptomycin and streptomycin, enrofloxacin, gentamicin, neomycin, oxolinic acid and spiramycin) a glucocorticosteroid (dexamethasone), and a tranquilizing agent (azaperone). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily intakes and Maximum Residue Limits, and a list of further toxicological studies and other information required or desired. PMID:8585227

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

    PubMed

    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

  15. The effect of cooking on veterinary drug residues in food; 5. Oxfendazole.

    PubMed

    Rose, M D; Shearer, G; Farrington, W H

    1997-01-01

    The heat stability of the anthelmintic oxfendazole in water, cooking oil and as incurred residues in cattle liver was investigated. Some evidence of instability was found in boiling water after 3 h. This degradation was associated with the formation of a product which was identified by mass spectrometry as the amine formed by hydrolysis of the carbamate functional group on the oxfendazole molecule. In hot cooking oil at 150 degrees C and 180 degrees C the half-life of oxfendazole was 15 min and 6 min respectively. The amine was also shown to form in oil as the concentration of oxfendazole depleted. The effects of cooking on incurred residues of oxfendazole in cattle liver were inconclusive from this study. Several variable factors were found to be in place including: an unstable equilibrium between oxfendazole, oxfendazole sulphone and fenbendazole in incurred tissue; the overall instability of these compounds in tissue during frozen storage for the duration of the project; the distribution of the residues within the tissue used for the study and the effect of protein binding on extractability of residues from the tissue. It was nevertheless found that: (i) cooking did not destroy residues although it may affect the point of equilibrium between oxfendazole, oxfendazole sulphone, fenbendazole and some other metabolites in incurred tissue; (ii) the amine derivative was not observed in raw incurred tissue; (iii) residues were not evenly distributed in raw incurred tissue; (iv) storage time affected the measured residue concentration either because of losses or protein binding or a combination of both.

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

    PubMed

    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.

  17. Evaluation of certain veterinary drug residues in food. Seventy-eighth report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    2014-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues of food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including extrapolation of maximum residue limits (MRLs) to minor species, MRLs for veterinary drug residues in honey, MRLs relating to fish and fish species, dietary exposure assessment methodologies, the decision-tree approach to the evaluation of residues of veterinary drugs and guidance for JECFA experts. Summaries follow of the Committee's evaluations of toxicology and residue data on a variety of veterinary drugs: two anthelminthic agents (derquantel, monepantel), three antiparasitic agents (emanectin benzoate, ivermectin, lasalocid sodium), one antibacterial, antifungal and anthelminthic agent (gentian violet), a production aid (recombinant bovine somatotropins) and an adrenoceptor agonist and growth promoter (zilpaterol hydorchloride). Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs)) and proposed MRLs. PMID:25591324

  18. Multi-residue determination of 210 drugs in pork by ultra-high-performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Yin, Zhiqiang; Chai, Tingting; Mu, Pengqian; Xu, Nana; Song, Yue; Wang, Xinlu; Jia, Qi; Qiu, Jing

    2016-09-01

    This paper presents a multi-residue analytical method for 210 drugs in pork using ultra-high-performance liquid chromatography-Q-Trap tandem mass spectrometry (UPLC-MS/MS) within 20min via positive ESI in scheduled multi-reaction monitoring (MRM) mode. The 210 drugs, belonging to 21 different chemical classes, included macrolides, sulfonamides, tetracyclines, β-lactams, β-agonists, aminoglycosides, antiviral drugs, glycosides, phenothiazine, protein anabolic hormones, non-steroidal anti-inflammatory drugs (NSAIDs), quinolones, antifungal drugs, corticosteroids, imidazoles, piperidines, piperazidines, insecticides, amides, alkaloids and others. A rapid and simple preparation method was applied to process the animal tissues, including solvent extraction with an acetonitrile/water mixture (80/20, v/v), defatting and clean-up processes. The recoveries ranged from 52% to 130% with relative standard deviations (RSDs)<20% for spiked concentrations of 10, 50 and 250μg/kg. More than 90% of the analytes achieved low limits of quantification (LOQs)<10μg/kg. The decision limit (CCα), detection capability (CCβ) values were in the range of 2-502μg/kg and 4-505μg/kg, respectively. This method is significant for food safety monitoring and controlling veterinary drug use. PMID:27499107

  19. Evaluation of certain veterinary drug residues in food. Forty-eighth report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    1998-01-01

    This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in foods and to recommend maximum levels for such residues in food. The first part of the report considers standards for the performance of studies, residues at the injection site, and several initiatives to promote transparency of the process for setting Maximum Residue Limits (MRLs). A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two anthelminthic agents (moxidectin and tiabendazole), eight antimicrobial agents (ceftiofur, danofloxacin, dihydrostreptomycin, streptomycin, enrofloxacin, flumequine, gentamicin and spiramycin), one glucocorticosteroid (dexamethasone), and two insecticides (cyfluthrin and fluazuron). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and MRL's and further toxicological studies and other information required.

  20. Evaluation of certain veterinary drug residues in food. Forty-eighth report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    1998-01-01

    This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in foods and to recommend maximum levels for such residues in food. The first part of the report considers standards for the performance of studies, residues at the injection site, and several initiatives to promote transparency of the process for setting Maximum Residue Limits (MRLs). A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two anthelminthic agents (moxidectin and tiabendazole), eight antimicrobial agents (ceftiofur, danofloxacin, dihydrostreptomycin, streptomycin, enrofloxacin, flumequine, gentamicin and spiramycin), one glucocorticosteroid (dexamethasone), and two insecticides (cyfluthrin and fluazuron). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and MRL's and further toxicological studies and other information required. PMID:9727328

  1. Evaluation of certain veterinary drug residues in food. Fiftieth report of the joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    1999-01-01

    This report presents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues. The first part of the report considers the neurotoxicity of anthelminthics belonging to the avermectin and milbemycin classes of compounds and the evaluation policy of the Committee in establishing Maximum Residue Levels (MRLs) for veterinary drugs in food. A summary follows of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: five anthelminthic agents (eprinomectin, febantel, fenbendazole, oxfendazole and moxidectin), seven antimicrobial agents (gentamicin, procaine benzylpenicillin, sarafloxacin, spectinomycin, chlortetracycline, oxytetracycline and tetracycline), three antiprotozoal agents (diclazuril, imidocarb and nicarbazin), one glucocorticosteroid (dexamethasone), one production aid (recombinant bovine somatotropins) and one tranquilizing agent (azaperone). Annexed to the report are a summary of the Committee's recommendations on these drugs, including Acceptable Daily Intakes and MRLs, and further toxicological studies and other information required. PMID:10416362

  2. Anthelmintic drug residues in beef: UPLC-MS/MS method validation, European retail beef survey, and associated exposure and risk assessments.

    PubMed

    Cooper, K M; Whelan, M; Kennedy, D G; Trigueros, G; Cannavan, A; Boon, P E; Wapperom, D; Danaher, M

    2012-01-01

    Anthelmintic drugs are widely used to control parasitic infections in cattle. The ProSafeBeef project addressed the need for data on the exposure of European consumers of beef to potentially harmful drug residues. A novel analytical method based on matrix solid-phase dispersive extraction and ultra-performance liquid chromatography-tandem mass spectrometry was validated for 37 anthelmintic drugs and metabolites in muscle (assay decision limits, CCα, = 0.15-10.2 µg kg⁻¹). Seven European countries (France, Spain, Slovenia, Ireland, Italy, Belgium and Portugal) participated in a survey of retail beef purchased in local shops. Of 1061 beef samples analysed, 26 (2.45%) contained detectable residues of anthelmintic drugs (0.2-171 µg kg⁻¹), none above its European Union maximum residue limit (MRL) or action level. Residues detected included closantel, levamisole, doramectin, eprinomectin, moxidectin, ivermectin, albendazole and rafoxanide. In a risk assessment applied to mean residue concentrations across all samples, observed residues accounted for less than 0.1% of the MRL for each compound. An exposure assessment based on the consumption of meat at the 99th percentile of consumption of adults in 14 European countries demonstrated that beef accounted for less than 0.02% of the acceptable daily intake for each compound in each country. This study is the first of its kind to apply such a risk-based approach to an extensive multi-residue survey of veterinary drug residues in food. It has demonstrated that the risk of exposure of the European consumer to anthelmintic drug residues in beef is negligible, indicating that regulation and monitoring is having the desired effect of limiting residues to non-hazardous concentrations.

  3. 21 CFR 556.1 - General considerations; tolerances for residues of new animal drugs in food.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of analysis in any edible portion of such animals after slaughter or in any food yielded by or... drugs in edible products of food-producing animals treated with such drugs. Consideration of an... in the edible products—in which case a finite tolerance is required; or (2) It is not possible...

  4. Evaluation of certain veterinary drug residues in food. Eighty-first report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    2016-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including MRLs for generic fish species, acute reference doses (ARfDs) for veterinary drugs, an approach for dietary exposure assessment of compounds used for multiple purposes (i.e veterinary drugs and pesticides), dietary exposure assessment for less-than-lifetime exposure, and the assessment of short-term (90-day and 12-month) studies in dogs. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two insecticides (diflubenzuron and teflubenzuron), an antiparasitic agent (ivermectin), an ectoparasiticide (sisapronil) and a β2-adrenoceptor agonist (zilpaterol hydrochloride). In addition, the Committee considered issues raised in concern forms from the Codex Committee on Residues of Veterinary Drugs in Foods on lasalocid sodium, an antiparasitic agent. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs), ARfDs and proposed MRLs. PMID:27509597

  5. Evaluation of certain veterinary drug residues in food. Eighty-first report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    2016-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of residues of veterinary drugs within the terms of reference of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), including MRLs for generic fish species, acute reference doses (ARfDs) for veterinary drugs, an approach for dietary exposure assessment of compounds used for multiple purposes (i.e veterinary drugs and pesticides), dietary exposure assessment for less-than-lifetime exposure, and the assessment of short-term (90-day and 12-month) studies in dogs. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: two insecticides (diflubenzuron and teflubenzuron), an antiparasitic agent (ivermectin), an ectoparasiticide (sisapronil) and a β2-adrenoceptor agonist (zilpaterol hydrochloride). In addition, the Committee considered issues raised in concern forms from the Codex Committee on Residues of Veterinary Drugs in Foods on lasalocid sodium, an antiparasitic agent. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes (ADIs), ARfDs and proposed MRLs.

  6. Global connectivity of hub residues in Oncoprotein structures encodes genetic factors dictating personalized drug response to targeted Cancer therapy

    NASA Astrophysics Data System (ADS)

    Soundararajan, Venky; Aravamudan, Murali

    2014-12-01

    The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action - inspired by the Google page rank algorithm that unearths most ``globally connected'' websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to identify amino acid residue hubs whose global connectivity dynamics are characteristic of the ligand or mutation associated with the target protein. We find that unexpected allosteric hubs - up to 20Å from the ATP binding site, but within 5Å of the phosphorylation site - encode the Gibbs free energy of inhibition (ΔGinhibition) for select protein kinase-targeted cancer therapeutics. We further find that clinically relevant somatic cancer mutations implicated in both drug resistance and personalized drug sensitivity can be predicted in a high-throughput fashion. Our results establish global connectivity analysis as a potent assay of protein functional modulation. This sets the stage for unearthing disease-causal exome mutations and motivates forecast of clinical drug response on a patient-by-patient basis. We suggest incorporation of structure-guided genetic inference assays into pharmaceutical and healthcare Oncology workflows.

  7. Global connectivity of hub residues in Oncoprotein structures encodes genetic factors dictating personalized drug response to targeted Cancer therapy

    PubMed Central

    Soundararajan, Venky; Aravamudan, Murali

    2014-01-01

    The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action – inspired by the Google page rank algorithm that unearths most “globally connected” websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to identify amino acid residue hubs whose global connectivity dynamics are characteristic of the ligand or mutation associated with the target protein. We find that unexpected allosteric hubs – up to 20Å from the ATP binding site, but within 5Å of the phosphorylation site – encode the Gibbs free energy of inhibition (ΔGinhibition) for select protein kinase-targeted cancer therapeutics. We further find that clinically relevant somatic cancer mutations implicated in both drug resistance and personalized drug sensitivity can be predicted in a high-throughput fashion. Our results establish global connectivity analysis as a potent assay of protein functional modulation. This sets the stage for unearthing disease-causal exome mutations and motivates forecast of clinical drug response on a patient-by-patient basis. We suggest incorporation of structure-guided genetic inference assays into pharmaceutical and healthcare Oncology workflows. PMID:25465236

  8. Evaluation of certain veterinary drug residues in food. Sixty-sixth report of the Joint FAO/WHO Expert Committee on Food Additives.

    PubMed

    2006-01-01

    This report represents the conclusions of a Joint FAO/WHO Expert Committee convened to evaluate the safety of residues of certain veterinary drugs in food and to recommend maximum levels for such residues in food. The first part of the report considers general principles regarding the evaluation of veterinary drugs within the terms of reference of JECFA, including compounds without an ADI or MRL; recommendations on principles and methods in derivation of MRLs, including a new procedure for estimating chronic dietary intakes; the use of a spreadsheet-based procedure for the statistical evaluation of residue depletion data; a revised approach for the derivation of microbiological ADIs; and the Committee's review of and comments on documents provided by the Codex Committee on Residues of Veterinary Drugs. Summaries follow of the Committee's evaluations of toxicological and residue data on a variety of veterinary drugs: three antimicrobial agents (colistin, erythromycin, flumequine), two production aids (melengestrol acetate, ractopamine hydrochloride), an insecticide (trichlorfon (metrifonate)) and an anthelminthic (triclabendazole). In addition, the attempt by the Committee to use tylosin as an example to investigate if evaluations are possible based on published data in the absence of data submissions from sponsors is described. Annexed to the report is a summary of the Committee's recommendations on these drugs, including acceptable daily intakes and proposed maximum residue limits. PMID:17373572

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

    PubMed

    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.

  10. Closantel plasma and milk disposition in dairy goats: assessment of drug residues in cheese and ricotta.

    PubMed

    Iezzi, S; Lifschitz, A; Sallovitz, J; Nejamkin, P; Lloberas, M; Manazza, J; Lanusse, C; Imperiale, F

    2014-12-01

    Closantel (CLS) is currently used in programs for the strategic control of gastrointestinal nematodes. CLS is extralabel used in different dairy goat production systems. From available data in dairy cows, it can be concluded that residues of CLS persist in milk. The current work evaluated the concentration profiles of CLS in plasma and milk from lactating orally treated dairy goats to assess the residues pattern in dairy products such as cheese and ricotta. Six (6) female Saanen dairy goats were treated orally with CLS administered at 10 mg/kg. Blood and milk samples were collected between 0 and 36 days post-treatment. The whole milk production was collected at 1, 4, 7, and 10 days post-treatment to produce soft cheese and ricotta. CLS concentrations in plasma, milk, cheese, whey, and ricotta were determined by HPLC. The concentrations of CLS measured in plasma were higher than those measured in milk at all sampling times. However, the calculated withdrawal time for CLS in milk was between 39 and 43 days postadministration to dairy goats. CLS residual concentrations in cheese (between 0.93 and 1.8 μg/g) were higher than those measured in the milk used for its production. CLS concentrations in ricotta were sixfold higher than those in the milk and 20-fold higher than those in the whey used for its production. The persistent and high residual concentrations of CLS in the milk and in the cheese and ricotta should be seriously considered before issuing any recommendation on the extralabel use of CLS in dairy goat farms.

  11. Multi-residue Determination of Polar Veterinary Drugs in Livestock and Fishery Products by Liquid Chromatography/Tandem Mass Spectrometry.

    PubMed

    Kanda, Maki; Nakajima, Takayuki; Hayashi, Hiroshi; Hashimoto, Tsuneo; Kanai, Setsuko; Nagano, Chieko; Matsushima, Yoko; Tateishi, Yukinari; Yoshikawa, Soichi; Tsuruoka, Yumi; Sasamoto, Takeo; Takano, Ichiro

    2015-01-01

    Residues of 37 polar veterinary drugs belonging to six families (quinolones, tetracyclines, macrolides, lincosamides, sulfonamides, and others) in livestock and fishery products were determined using a validated LC-MS/MS method. There were two key points in sample preparation. First, extraction was performed with two solutions of different polarity. Highly polar compounds were initially extracted with Na2EDTA-McIlvaine's buffer (pH 7.0). Medium polar compounds were then extracted from the same samples with acetonitrile containing 0.1% formic acid. Secondly, cleanup was performed using a single SPE polymer cartridge. The first extracted solution was applied to the cartridge. Highly polar compounds were retained on the cartridge. Then, the second extracted solution was applied to the same cartridge. Both highly and medium polar compounds were eluted from the cartridge. This method satisfied the guideline criteria for 37 out of 37 drugs in swine muscle, chicken muscle, bovine muscle, prawn, salmon trout, red sea bream, milk, and honey; 35 out of 37 in egg; and 34 out of 37 in flounder. The LOQ ranged from 0.1 to 5 μg/kg. Residues were detected in 24 out of 110 samples and analyzed using the validated method.

  12. Source discrimination of drug residues in wastewater: The case of salbutamol.

    PubMed

    Depaolini, Andrea Re; Fattore, Elena; Cappelli, Francesca; Pellegrino, Raffaele; Castiglioni, Sara; Zuccato, Ettore; Fanelli, Roberto; Davoli, Enrico

    2016-06-15

    Analytical methods used for pharmaceuticals and drugs of abuse in sewage play a fundamental role in wastewater-based epidemiology (WBE) studies. Here quantitative analysis of drug metabolites in raw wastewaters is used to determine consumption from general population. Its great advantage in public health studies is that it gives objective, real-time data about community use of chemicals, highlighting the relationship between environmental and human health. Within a WBE study on salbutamol use in a large population, we developed a procedure to distinguish human metabolic excretion from external source of contamination, possibly industrial, in wastewaters. Salbutamol is mainly excreted as the sulphate metabolite, which is rapidly hydrolyzed to the parent compound in the environment, so this is currently not detected. When a molecule is either excreted un-metabolized or its metabolites are unstable in the environment, studies can be completed by monitoring the parent compound. In this case it is mandatory to assess whether the drug in wastewater is present because of population use or because of a specific source of contamination, such as industrial manufacturing waste. Because commercial salbutamol mainly occurs as a racemic mixture and is stereoselective in the human metabolism, the enantiomeric relative fraction (EFrel) in wastewater samples should reflect excretion, being unbalanced towards one of two enantiomers, if the drug is of metabolic origin. The procedure described involves chiral analysis of the salbutamol enantiomers by liquid chromatography-tandem mass spectrometry (LC-MS-MS) and calculation of EFrel, to detect samples where external contamination occurs. Samples were collected daily between October and December 2013 from the Milano Nosedo wastewater treatment plant. Carbamazepine and atenolol were measured in the sewage collector, as "control" drugs. Salbutamol EFrel was highly consistent in all samples during this three-month period, but a limited

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

    PubMed

    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

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

    PubMed

    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

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

    PubMed

    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.

  16. Direct analyte-probed nanoextraction coupled to nanospray ionization-mass spectrometry of drug residues from latent fingerprints.

    PubMed

    Clemons, Kristina; Wiley, Rachel; Waverka, Kristin; Fox, James; Dziekonski, Eric; Verbeck, Guido F

    2013-07-01

    Here, we present a method of extracting drug residues from fingerprints via Direct Analyte-Probed Nanoextraction coupled to nanospray ionization-mass spectrometry (DAPNe-NSI-MS). This instrumental technique provides higher selectivity and lower detection limits over current methods, greatly reducing sample preparation, and does not compromise the integrity of latent fingerprints. This coupled to Raman microscopy is an advantageous supplement for location and identification of trace particles. DAPNe uses a nanomanipulator for extraction and differing microscopies for localization of chemicals of interest. A capillary tip with solvent of choice is placed in a nanopositioner. The surface to be analyzed is placed under a microscope, and a particle of interest is located. Using a pressure injector, the solvent is injected onto the surface where it dissolves the analyte, and then extracted back into the capillary tip. The solution is then directly analyzed via NSI-MS. Analyses of caffeine, cocaine, crystal methamphetamine, and ecstasy have been performed successfully.

  17. Assessment of MEKC suitability for residue drug monitoring on pharmaceutical manufacturing equipment.

    PubMed

    Boca, Madalina Brindusa; Pretorius, Etheresia; Kgaje, Christopher; Apostolides, Zeno

    2008-03-13

    The suitability of micellar electrokinetic chromatography for the simultaneous trace determination of several compounds (sulfamethoxazole, trimethoprim, sulfanilic acid, sulfanilamide, 3,4,5-trimethoxybenzoic acid and nonoxynol-9) was assessed. The mixture was separated within 14min at an applied voltage of 22kV by using 30mM phosphate electrolyte, containing 10mM SDS, adjusted to pH 7.8. Under optimized separation conditions acceptable levels of linearity, precision and accuracy were obtained for all compounds. The method could be used as part of a cleaning validation study when assaying trace levels of co-trimoxazole drug, some of its decomposition products and detergent in the swab samples collected from pharmaceutical manufacturing equipment, after cleaning. PMID:18178359

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

    NASA Astrophysics Data System (ADS)

    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).

  19. Hepatotoxicity of Pentavalent Antimonial Drug: Possible Role of Residual Sb(III) and Protective Effect of Ascorbic Acid

    PubMed Central

    Kato, Kelly C.; Morais-Teixeira, Eliane; Reis, Priscila G.; Silva-Barcellos, Neila M.; Salaün, Pascal; Campos, Paula P.; Dias Corrêa-Junior, José; Rabello, Ana; Demicheli, Cynthia

    2014-01-01

    Pentavalent antimonial drugs such as meglumine antimoniate (Glucantime [Glu; Sanofi-Aventis, São Paulo, Brazil]) produce severe side effects, including cardiotoxicity and hepatotoxicity, during the treatment of leishmaniasis. We evaluated the role of residual Sb(III) in the hepatotoxicity of meglumine antimoniate, as well as the protective effect of the antioxidant ascorbic acid (AA) during antimonial chemotherapy in a murine model of visceral leishmaniasis. BALB/c mice infected with Leishmania infantum were treated intraperitoneally at 80 mg of Sb/kg/day with commercial meglumine antimoniate (Glu) or a synthetic meglumine antimoniate with lower Sb(III) level (MA), in association or not with AA (15 mg/kg/day), for a 20-day period. Control groups received saline or saline plus AA. Livers were evaluated for hepatocytes histological alterations, peroxidase activity, and apoptosis. Increased proportions of swollen and apoptotic hepatocytes were observed in animals treated with Glu compared to animals treated with saline or MA. The peroxidase activity was also enhanced in the liver of animals that received Glu. Cotreatment with AA reduced the extent of histological changes, the apoptotic index, and the peroxidase activity to levels corresponding to the control group. Moreover, the association with AA did not affect the hepatic uptake of Sb and the ability of Glu to reduce the liver and spleen parasite loads in infected mice. In conclusion, our data supports the use of pentavalent antimonials with low residue of Sb(III) and the association of pentavalent antimonials with AA, as effective strategies to reduce side effects in antimonial therapy. PMID:24189251

  20. Analysis of veterinary drug residues in shrimp: a multi-class method by liquid chromatography-quadrupole ion trap mass spectrometry.

    PubMed

    Li, Hui; Kijak, Philip James; Turnipseed, Sherri B; Cui, Wei

    2006-05-19

    A liquid chromatography-mass spectrometry (LC-MS) method was developed to screen and confirm veterinary drug residues in raw shrimp meat. This method simultaneously monitors 18 drugs of different classes, including oxytetracycline (OTC), sulfonamides, quinolones, cationic dyes, and toltrazuril sulfone (TOLS). The homogenized shrimp meat is extracted with 5% trichloroacetic acid. The extract is further cleaned using polymer-based SPE. A 50 mm phenyl column separates the analytes, prior to analysis with an ion trap mass spectrometer interfaced with an atmospheric pressure chemical ionization source. This method is able to confirm oxytetracycline residues at 200 ng/g, toltrazuril sulfone at 50 ng/g, sulfaquinoxaline at 20 ng/g, and the other 15 drugs at 10 ng/g or lower levels. An estimate of the level of residues can also be made so that only confirmed samples above action levels will be sent for quantitation. The method is validated with both fortified and incurred samples, using multiple shrimp species as well. This multi-class method can provide a means to simultaneously monitor for a wide range of illegal drug residues in shrimp. PMID:16597519

  1. The effect of administering long-acting oxytetracycline and tilmicosin either by dart gun or by hand on injection site lesions and drug residues in beef cattle.

    PubMed Central

    Van Donkersgoed, J; VanderKop, M; Salisbury, C; Sears, L; Holowath, J

    1999-01-01

    Forty yearling cattle were injected intramuscularly with long-acting oxytetracycline and subcutaneously with tilmicosin by dart gun or by hand in a chute 28 days prior to slaughter. The drugs caused injection site lesions and antibiotic residues in the neck and thigh that varied by technique, dose, and site. PMID:12001341

  2. Ruggedness testing and validation of a practical analytical method for > 100 veterinary drug residues in bovine muscle by ultrahigh performance liquid chromatography – tandem mass spectrometry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, optimization, extension, and validation of a streamlined, qualitative and quantitative multiclass, multiresidue method was conducted to monitor great than100 veterinary drug residues in meat using ultrahigh-performance liquid chromatography – tandem mass spectrometry (UHPLC-MS/MS). I...

  3. An update discussion on the current assessment of the safety of veterinary antimicrobial drug residues in food with regard to their impact on the human intestinal microbiome.

    PubMed

    Cerniglia, Carl E; Pineiro, Silvia A; Kotarski, Susan F

    2016-05-01

    The human gastrointestinal tract ecosystem consists of complex and diverse microbial communities that have now been collectively termed the intestinal microbiome. Recent scientific breakthroughs and research endeavours have increased our understanding of the important role the intestinal microbiome plays in human health and disease. The use of antimicrobial new animal drugs in food-producing animals may result in the presence of low levels of drug residues in edible foodstuffs. There is concern that antimicrobial new animal drugs in or on animal-derived food products at residue-level concentrations could disrupt the colonization barrier and/or modify the antimicrobial resistance profile of human intestinal bacteria. Therapeutic doses of antimicrobial drugs have been shown to promote shifts in the intestinal microbiome, and these disruptions promote the emergence of antimicrobial-resistant bacteria. To assess the effects of antimicrobial new animal drug residues in food on human intestinal bacteria, many national regulatory agencies and international committees follow a harmonized process, VICH GL36(R), which was issued by a trilateral organization of the European Union, the USA, and Japan called the International Cooperation on Harmonization of Technical Requirements for Veterinary Medicinal Products (VICH). The guidance describes a general approach currently used by national regulatory agencies and international committees to assess the effects of antimicrobial new animal drug residues in animal-derived food on human intestinal bacteria. The purpose of this review is to provide an overview of this current approach as part of the antimicrobial new animal drug approval process in participating countries, give insights on the microbiological endpoints used in this safety evaluation, and discuss the availability of new information. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27443209

  4. Analysis of drug residues in tissue by combined supercritical-fluid extraction-supercritical-fluid chromatography-mass spectrometry-mass spectrometry.

    PubMed

    Ramsey, E D; Perkins, J R; Games, D E; Startin, J R

    1989-03-01

    The combination of supercritical-fluid extraction-supercritical-fluid chromatography-tandem mass spectrometry has been evaluated for the detection of residues of a small group of veterinary drugs in freeze-dried pig's kidney. During extraction with supercritical CO2 the drugs were retained by the column while non-polar endogenous material was not retained and thus passed to waste. Subsequent changes to the mobile phase composition eluted the drugs which were detected with high specificity by tandem mass spectrometry. Although the sensitivity in this preliminary study was not adequate for surveillance or enforcement, there is potential for further development of the approach.

  5. [Effects of long-term application of pig manure containing residual tetracycline on the formation of drug-resistant bacteria and resistance genes].

    PubMed

    Zhang, Jun; Yang, Xiao-Hong; Ge, Feng; Wang, Na; Jiao, Shao-Jun; Jiao, Shao-Jun

    2014-06-01

    The effect of residual veterinary tetracycline on the formation of drug-resistant bacteria and corresponding resistance genes was investigated. During the research, the soil with long-term application of pig manure containing residual tetracycline was collected in autumn and summer respectively in the farmland around a certain pig farm in Shuyang City, Huang Huai area, north of Jiangsu province. At the same time, soils without application of pig manure in the farmland of this area were collected as the reference sample. Composition of drug-resistant bacteria in all soil samples was analyzed and three common tetracycline-resistance genes (tetA, tetC, tetE) were studied by PCR as well. During the research, 59 drug-resistant bacteria belonging to 13 bacterial genus respectively were separated from the soil sample collected in autumn while 35 drug- resistant bacteria belonging to 10 bacterial genus respectively were separated from the soil sample collected in summer and as for the reference sample, 3 drug-resistant bacteria belonging to 1 bacterial genus (Streptomyces) were separated with pathogenic bacteria up to 38.14% of total drug-resistant bacteria. PCR result showed that resistance genes were detected in all drug-resistant bacteria and tetC accounted for the most. At the same time, the residual tetracycline in the soil which was in a range of 41.1-61.9 microg x kg(-1) correlated with the amount of resistance genes (4.63 x 10(5)-37.42 x 10(5) copies x g(-1)). Besides, the climate was found accelerating the formation of drug-resistant bacteria and resistance genes.

  6. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance

    PubMed Central

    Balko, Justin M; Cook, Rebecca S; Vaught, David B; Kuba, María G; Miller, Todd W; Bhola, Neil E; Sanders, Melinda E; Granja-Ingram, Nara M; Smith, J Joshua; Meszoely, Ingrid M; Salter, Janine; Dowsett, Mitch; Stemke-Hale, Katherine; González-Angulo, Ana M; Mills, Gordon B; Pinto, Joseph A; Gómez, Henry L; Arteaga, Carlos L

    2012-01-01

    Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ~30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy. PMID:22683778

  7. Profiling of residual breast cancers after neoadjuvant chemotherapy identifies DUSP4 deficiency as a mechanism of drug resistance.

    PubMed

    Balko, Justin M; Cook, Rebecca S; Vaught, David B; Kuba, María G; Miller, Todd W; Bhola, Neil E; Sanders, Melinda E; Granja-Ingram, Nara M; Smith, J Joshua; Meszoely, Ingrid M; Salter, Janine; Dowsett, Mitch; Stemke-Hale, Katherine; González-Angulo, Ana M; Mills, Gordon B; Pinto, Joseph A; Gómez, Henry L; Arteaga, Carlos L

    2012-07-01

    Neoadjuvant chemotherapy (NAC) induces a pathological complete response (pCR) in ~30% of patients with breast cancer. However, many patients have residual cancer after chemotherapy, which correlates with a higher risk of metastatic recurrence and poorer outcome than those who achieve a pCR. We hypothesized that molecular profiling of tumors after NAC would identify genes associated with drug resistance. Digital transcript counting was used to profile surgically resected breast cancers after NAC. Low concentrations of dual specificity protein phosphatase 4 (DUSP4), an ERK phosphatase, correlated with high post-NAC tumor cell proliferation and with basal-like breast cancer (BLBC) status. BLBC had higher DUSP4 promoter methylation and gene expression patterns of Ras-ERK pathway activation relative to other breast cancer subtypes. DUSP4 overexpression increased chemotherapy-induced apoptosis, whereas DUSP4 depletion dampened the response to chemotherapy. Reduced DUSP4 expression in primary tumors after NAC was associated with treatment-refractory high Ki-67 scores and shorter recurrence-free survival. Finally, inhibition of mitogen-activated protein kinase kinase (MEK) synergized with docetaxel treatment in BLBC xenografts. Thus, DUSP4 downregulation activates the Ras-ERK pathway in BLBC, resulting in an attenuated response to anti-cancer chemotherapy.

  8. Quantification of residual enrofloxacin and ciprofloxacin in feathers of broiler chickens by high-performance liquid chromatography-fluorescence after oral administration of the drugs

    PubMed Central

    Haag, Griselda; Marin, Gustavo H.; Errecalde, Jorge

    2016-01-01

    Enrofloxacin (ENR) and ciprofloxacin (CIP) are drugs used in poultry feeding. In general, feathers that are incorporated in the food chain as a protein source for animal feed, have residues of these drugs. In order to study the pharmacokinetic of ENR/CIP residues in feathers of broiler chickens, to calculate the waiting times for these drugs, before human consumption, we developed the present research. Feathers of broiler chickens were enriched with ENR/CIP. After adding acetone, the mix was agitated and centrifuged and supernatant evaporated under nitrogen. The dry residue was suspended in a tetrahydrofuran solution and the supernatant was injected into the chromatographic system for analysis. Animals showed high levels of ENR/CIP in their feathers after administration of 10 mg/kg enrofloxacin dissolved in drinking water for 5 days. Both compounds were detected in feathers during 9 days. The analytical method developed in this paper to determine ENR and CIP in feathers of broiler chicken showed good linearity, selectivity, accuracy and precision in the analysis conditions. This technique could have important applications in the studies on residues of ENR/CIP in feathers, since the effect of this component in animal diets has not been considered yet. PMID:26955603

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

    PubMed

    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. PMID:26585470

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

    PubMed

    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.

  11. An update on ABCB1 pharmacogenetics: insights from a 3D model into the location and evolutionary conservation of residues corresponding to SNPs associated with drug pharmacokinetics.

    PubMed

    Wolf, S J; Bachtiar, M; Wang, J; Sim, T S; Chong, S S; Lee, C G L

    2011-10-01

    The human ABCB1 protein, (P-glycoprotein or MDR1) is a membrane-bound glycoprotein that harnesses the energy of ATP hydrolysis to drive the unidirectional transport of substrates from the cytoplasm to the extracellular space. As a large range of therapeutic agents are known substrates of ABCB1 protein, its role in the onset of multidrug resistance has been the focus of much research. This role has been of particular interest in the field of pharmacogenomics where genetic variation within the ABCB1 gene, particularly in the form of single nucleotide polymorphisms (SNPs), is believed to contribute to inter-individual variation in ABCB1 function and drug response. In this review we provide an update on the influence of coding region SNPs within the ABCB1 gene on drug pharmacokinetics. By utilizing the crystal structure of the mouse ABCB1 homolog (Abcb1a), which is 87% homologous to the human sequence, we accompany this discussion with a graphical representation of residue location for amino acids corresponding to human ABCB1 coding region SNPs. Also, an assessment of residue conservation, which is calculated following multiple sequence alignment of 11 confirmed sequences of ABCB1 homologs, is presented and discussed. Superimposing a 'heat map' of residue homology to the Abcb1a crystal structure has permitted additional insights into both the conservation of individual residues and the conservation of their immediate surroundings. Such graphical representation of residue location and conservation supplements this update of ABCB1 pharmacogenetics to help clarify the often confounding reports on the influence of ABCB1 polymorphisms on drug pharmacokinetics and response.

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

    PubMed

    Kaplun, Veronika; Stepensky, David

    2014-08-01

    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

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

    PubMed

    Kaplun, Veronika; Stepensky, David

    2014-08-01

    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

  14. Determination of small halogenated carboxylic acid residues in drug substances by high performance liquid chromatography-diode array detection following derivatization with nitro-substituted phenylhydrazines.

    PubMed

    Hou, Desheng; Fan, Jingjing; Han, Lingfei; Ruan, Xiaoling; Feng, Feng; Liu, Wenyuan; Zheng, Feng

    2016-03-18

    A method for the determination of small halogenated carboxylic acid (HCA) residues in drug substances is urgently needed because of the potential of HCAs for genotoxicity and carcinogenicity in humans. We have now developed a simple method, involving derivatization followed by high performance liquid chromatography-diode array detection (HPLC-DAD), for the determination of six likely residual HCAs (monochloroacetic acid, monobromoacetic acid, dichloroacetic acid, 2-chloropropionic acid, 2-bromopropionic acid and 3-chloropropionic acid) in drug substances. Different nitro-substituted phenylhydrazines (NPHs) derivatization reagents were systematically compared and evaluated. 2-Nitrophenylhydrazine hydrochloride (2-NPH·HCl) was selected as the most suitable choice since its derivatives absorb strongly at 392 nm, a region of the spectrum where most drug substances and impurities absorb very weakly. During the derivatization process, the commonly used catalyst, pyridine, caused rapid dechlorination or chlorine substitution of α-halogenated derivatives. To avoid these unwanted side reactions, a reliable derivatization method that did not use pyridine was developed. Reaction with 2-NPH·HCl using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as coupling agent in acetonitrile-water (70:30) at room temperature for 2h gave complete reaction and avoided degradation products. The derivatives were analyzed, without any pretreatment, using gradient HPLC with detection in the near visible region. Organic acids commonly found in drug substances and other impurities did not interfere with the analysis. Good linearity (r>0.999) and low limits of quantitation (0.05-0.12 μg mL(-1)) were obtained. The mean recoveries were in the range of 80-115% with RSD <5.81% except for 3-CPA in ibuprofen which was 78.5%. The intra- and inter-day precisions were expressed as RSD <1.98% and <4.39%, respectively. Finally, the proposed method was successfully used for the residue

  15. Determination of small halogenated carboxylic acid residues in drug substances by high performance liquid chromatography-diode array detection following derivatization with nitro-substituted phenylhydrazines.

    PubMed

    Hou, Desheng; Fan, Jingjing; Han, Lingfei; Ruan, Xiaoling; Feng, Feng; Liu, Wenyuan; Zheng, Feng

    2016-03-18

    A method for the determination of small halogenated carboxylic acid (HCA) residues in drug substances is urgently needed because of the potential of HCAs for genotoxicity and carcinogenicity in humans. We have now developed a simple method, involving derivatization followed by high performance liquid chromatography-diode array detection (HPLC-DAD), for the determination of six likely residual HCAs (monochloroacetic acid, monobromoacetic acid, dichloroacetic acid, 2-chloropropionic acid, 2-bromopropionic acid and 3-chloropropionic acid) in drug substances. Different nitro-substituted phenylhydrazines (NPHs) derivatization reagents were systematically compared and evaluated. 2-Nitrophenylhydrazine hydrochloride (2-NPH·HCl) was selected as the most suitable choice since its derivatives absorb strongly at 392 nm, a region of the spectrum where most drug substances and impurities absorb very weakly. During the derivatization process, the commonly used catalyst, pyridine, caused rapid dechlorination or chlorine substitution of α-halogenated derivatives. To avoid these unwanted side reactions, a reliable derivatization method that did not use pyridine was developed. Reaction with 2-NPH·HCl using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride as coupling agent in acetonitrile-water (70:30) at room temperature for 2h gave complete reaction and avoided degradation products. The derivatives were analyzed, without any pretreatment, using gradient HPLC with detection in the near visible region. Organic acids commonly found in drug substances and other impurities did not interfere with the analysis. Good linearity (r>0.999) and low limits of quantitation (0.05-0.12 μg mL(-1)) were obtained. The mean recoveries were in the range of 80-115% with RSD <5.81% except for 3-CPA in ibuprofen which was 78.5%. The intra- and inter-day precisions were expressed as RSD <1.98% and <4.39%, respectively. Finally, the proposed method was successfully used for the residue

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

    PubMed

    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.

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

    PubMed

    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. PMID:27529828

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

    PubMed Central

    Imamoglu, Husniye; Oktem Olgun, Elmas

    2016-01-01

    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. PMID:27293962

  19. Analytical method for fast screening and confirmation of multi-class veterinary drug residues in fish and shrimp by LC-MS/MS.

    PubMed

    Kim, Junghyun; Suh, Joon Hyuk; Cho, Hyun-Deok; Kang, Wonjae; Choi, Yong Seok; Han, Sang Beom

    2016-01-01

    A multi-class, multi-residue analytical method based on LC-MS/MS detection was developed for the screening and confirmation of 28 veterinary drug and metabolite residues in flatfish, shrimp and eel. The chosen veterinary drugs are prohibited or unauthorised compounds in Korea, which were categorised into various chemical classes including nitroimidazoles, benzimidazoles, sulfones, quinolones, macrolides, phenothiazines, pyrethroids and others. To achieve fast and simultaneous extraction of various analytes, a simple and generic liquid extraction procedure using EDTA-ammonium acetate buffer and acetonitrile, without further clean-up steps, was applied to sample preparation. The final extracts were analysed by ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS). The method was validated for each compound in each matrix at three different concentrations (5, 10 and 20 ng g(-1)) in accordance with Codex guidelines (CAC/GL 71-2009). For most compounds, the recoveries were in the range of 60-110%, and precision, expressed as the relative standard deviation (RSD), was in the range of 5-15%. The detection capabilities (CCβs) were below or equal to 5 ng g(-1), which indicates that the developed method is sufficient to detect illegal fishery products containing the target compounds above the residue limit (10 ng g(-1)) of the new regulatory system (Positive List System - PLS). PMID:26751111

  20. Structural characterization of product ions by electrospray ionization and quadrupole time-of-flight mass spectrometry to support regulatory analysis of veterinary drug residues in foods Part 2: Benzimidazoles nitromidaz.....

    Technology Transfer Automated Retrieval System (TEKTRAN)

    RATIONALE: Analysis for identification and quantification of regulated veterinary drug residues in foods are usually achieved by liquid chromatography coupled to tandem mass spectrometry. The instrument method requires the selection of characteristic ions, but structure elucidation is seldom perform...

  1. 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

    PubMed Central

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud ES

    2016-01-01

    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 this work confirm that this new approach is favorable in the future of the drug design industry. PMID:27114700

  2. 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.

    PubMed

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud Es

    2016-01-01

    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 this work confirm that this new approach is favorable in the future of the drug design industry. PMID:27114700

  3. 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.

    PubMed

    Cele, Favourite N; Ramesh, Muthusamy; Soliman, Mahmoud Es

    2016-01-01

    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 this work confirm that this new approach is favorable in the future of the drug design industry.

  4. Molecularly imprinted solid-phase extraction for the determination of ten macrolide drugs residues in animal muscles by liquid chromatography-tandem mass spectrometry.

    PubMed

    Song, Xuqin; Zhou, Tong; Liu, Qingying; Zhang, Meiyu; Meng, Chenying; Li, Jiufeng; He, Limin

    2016-10-01

    A simple and sensitive method based on molecularly imprinted solid-phase extraction coupled with liquid chromatography-tandem mass spectrometry was developed for the determination of the residues of ten macrolide drugs in swine, cattle and chicken muscles samples. The molecularly imprinted polymers (MIPs) were synthesized using tylosin as a template and methacrylic acid as a functional monomer. Samples were extracted with sodium borate buffer solution and ethyl acetate, and purified by the MIP cartridge. The results showed that the cartridge exhibited good recognition performance for macrolides, and better purification effect than the traditional solid-phase extraction cartridges. Recoveries of analytes at three spiking levels 1, 5 and 20μgkg(-1) ranged from 60.7% to 100.3% with the relative standard deviations less than 14%. The limits of detection of the method were between 0.1 and 0.4μgkg(-1). The method is useful for the routine monitoring of the residues of macrolide drugs in animal muscles.

  5. 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.

    PubMed

    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. PMID:27443201

  6. 76 FR 16290 - Tolerances for Residues of New Animal Drugs in Food; 2-Acetylamino-5-Nitrothiazole; Buquinolate...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-23

    ...) and as Sec. 556.550 (40 FR 13802 at 13956). 12. Salicylic acid (Sec. 556.590). In 2005, FDA acknowledged the voluntary withdrawal of approval of salicylic acid for use in cattle under NADA 010-481 and...; Prednisolone; Prednisone; Progesterone; Propylparaben; and Salicylic Acid AGENCY: Food and Drug...

  7. Single-step extraction followed by LC for determination of (fluoro)quinolone drug residues in muscle, eggs, and milk.

    PubMed

    Cho, Hee-Jung; Yi, Hee; Cho, Soo Min; Lee, Dong Goo; Cho, Kyul; Abd el-Aty, A M; Shim, Jae-Han; Lee, Soon-Ho; Jeong, Ji-Yoon; Shin, Ho-Chul

    2010-04-01

    In this study, a simplified method for the extraction and determination of seven fluoroquinolone residues (danofloxacin, difloxacin, enrofloxacin, marbofloxacin, orbifloxacin, ofloxacin, and sarafloxacin) and three quinolones (oxolinic acid, flumequine, and nalidixic acid), in porcine muscle, table eggs, and commercial whole milk, which required no cleanup step, was devised. This procedure involves the extraction of analytes from the samples via liquid-phase extraction, and the subsequent quantitative determination was accomplished via LC-fluorescence detection. Analyte separation was successfully conducted on an XBridge-C(18) column, with a linear gradient mobile phase composed of acetonitrile and 0.01 M oxalic acid buffer at pH=3.5. The one-step liquid-liquid extraction method evidenced good selectivity, precision (RSDs=0.26-15.07%), and recovery of the extractable analytes, ranging from 61.12 to 115.93% in matrices. The LOQs ranged from 0.3 to 25 microg/kg. A survey of ten samples purchased from local markets was conducted, and none of the samples harbored fluoroquinolone residues. This method is an improvement over existing methodologies, since no additional cleanup was necessary.

  8. Identification of residues in ABCG2 affecting protein trafficking and drug transport, using co-evolutionary analysis of ABCG sequences

    PubMed Central

    Haider, Ameena J.; Cox, Megan H.; Jones, Natalie; Goode, Alice J.; Bridge, Katherine S.; Wong, Kelvin; Briggs, Deborah; Kerr, Ian D.

    2015-01-01

    ABCG2 is an ABC (ATP-binding cassette) transporter with a physiological role in urate transport in the kidney and is also implicated in multi-drug efflux from a number of organs in the body. The trafficking of the protein and the mechanism by which it recognizes and transports diverse drugs are important areas of research. In the current study, we have made a series of single amino acid mutations in ABCG2 on the basis of sequence analysis. Mutant isoforms were characterized for cell surface expression and function. One mutant (I573A) showed disrupted glycosylation and reduced trafficking kinetics. In contrast with many ABC transporter folding mutations which appear to be ‘rescued’ by chemical chaperones or low temperature incubation, the I573A mutation was not enriched at the cell surface by either treatment, with the majority of the protein being retained in the endoplasmic reticulum (ER). Two other mutations (P485A and M549A) showed distinct effects on transport of ABCG2 substrates reinforcing the role of TM helix 3 in drug recognition and transport and indicating the presence of intracellular coupling regions in ABCG2. PMID:26294421

  9. Drugs.

    ERIC Educational Resources Information Center

    Hurst, Hunter, Ed.; And Others

    1984-01-01

    This document contains the third volume of "Today's Delinquent," an annual publication of the National Center for Juvenile Justice. This volume deals with the issue of drugs and includes articles by leading authorities in delinquency and substance abuse who share their views on causes and cures for the drug problem among youth in this country.…

  10. [Determination of 9 cephalosporin drug residues in beef by ultra performance liquid chromatography-tandem mass spectrometry].

    PubMed

    Bai, Guotao; Chu, Xiaogang; Pan, Guoqing; Li, Xiuqin; Yong, Wei

    2009-07-01

    A confirmative method to determine 9 cephalosporin residues in beef by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed. The sample was homogenized and extracted with acetonitrile and water for 1 min at 14,000 r/min, centrifuged at 10,000 r/min and 4 degrees C for 10 min. A total of 2 mL saturated sodium chloride solution was added to avoid foaming during the acetonitrile evaporation, the acetonitrile was evaporated below 37 degrees C using a rotary evaporator, and then cleaned up on an Oasis HLB (500 mg, 6 mL) SPE column by washing with 5 mL water and eluting with acetonitrile-water (7:3, v/v). The eluate was blown to dryness under a stream of nitrogen and adjusted to 3.0 mL with water. The separation was carried out on an ACQUITY UPLC BEH C18 column within 5 min, analyzed by UPLC-MS/MS system with external standard method. The limits of quantification (LOQs) of cefuroxime, ceftiofur and cefalonium were 10, 0.5 and 0.5 microg/kg, respectively; the LOQs of other cephalosporins were 1.0 microg/kg. The recoveries of cephalosporins ranged from 74.2% to 119% and the relative standard deviations (RSDs) ranged from 2.9% to 15% for the spiked beef sample. The method is quick, easy, very sensitive and suitable for the determination of cephalosporin residues in beef.

  11. Rapid multi-residue and multi-class qualitative screening for veterinary drugs in foods of animal origin by UHPLC-MS/MS.

    PubMed

    Robert, C; Gillard, N; Brasseur, P-Y; Pierret, G; Ralet, N; Dubois, M; Delahaut, Ph

    2013-01-01

    Multi-class UHPLC-MS/MS was developed for the analysis of more than 160 regulated or banned compounds of various classes: anthelmintics including benzimidazoles, avermectins and others; antibiotics including amphenicols, beta-lactams, macrolides, pyrimidines, quinolones, sulphonamides and tetracyclines; beta-agonists; corticosteroids; ionophores; nitroimidazoles; non-steroidal anti-inflammatory agents; steroids; and tranquillisers. Samples were extracted with acetonitrile, without any additional purification step, and analysed by using UHPLC-MS/MS. Validation was done in accordance with the guidelines laid down by European Commission Decision 2002/657/EC for qualitative screening methods. This simple method proved applicable to routine screening for residues in egg, honey, milk and muscle samples at half the maximum concentration permitted by the European Union for each drug. In most cases, the target value was set at 5 µg kg(-1) for unauthorised compounds. PMID:23244466

  12. Rapid multi-residue and multi-class qualitative screening for veterinary drugs in foods of animal origin by UHPLC-MS/MS.

    PubMed

    Robert, C; Gillard, N; Brasseur, P-Y; Pierret, G; Ralet, N; Dubois, M; Delahaut, Ph

    2013-01-01

    Multi-class UHPLC-MS/MS was developed for the analysis of more than 160 regulated or banned compounds of various classes: anthelmintics including benzimidazoles, avermectins and others; antibiotics including amphenicols, beta-lactams, macrolides, pyrimidines, quinolones, sulphonamides and tetracyclines; beta-agonists; corticosteroids; ionophores; nitroimidazoles; non-steroidal anti-inflammatory agents; steroids; and tranquillisers. Samples were extracted with acetonitrile, without any additional purification step, and analysed by using UHPLC-MS/MS. Validation was done in accordance with the guidelines laid down by European Commission Decision 2002/657/EC for qualitative screening methods. This simple method proved applicable to routine screening for residues in egg, honey, milk and muscle samples at half the maximum concentration permitted by the European Union for each drug. In most cases, the target value was set at 5 µg kg(-1) for unauthorised compounds.

  13. Development of high-throughput multi-residue method for non-steroidal anti-inflammatory drugs monitoring in swine muscle by LC-MS/MS.

    PubMed

    Castilhos, Tamara S; Barreto, Fabiano; Meneghini, Leonardo; Bergold, Ana Maria

    2016-07-01

    A reliable and simple method for the detection and quantification of residues of 14 non-steroidal anti-inflammatory drugs and a metamizole metabolite in swine muscle was developed using liquid chromatography-electrospray ionisation-tandem mass spectrometry (LC-ESI-MS/MS). The samples were extracted with acetonitrile (ACN) in solid-liquid extraction followed by a low-temperature partitioning (LLE-LTP) process at -20 ± 2°C. After evaporation to dryness, the residue was reconstituted with hexane and a mixture of water:acetonitrile (1:1). LC separation was achieved on a reversed-phase (RP18) column with gradient elution using water (phase A) and ACN (phase B) both containing 1 mmol l(-)(1) ammonium acetate (NH4COO) with 0.025% acetic acid. Analysis was carried out on a triple-quadrupole tandem mass spectrometer (LC-MS/MS) in multiple reaction monitoring mode using an electrospray interface in negative and positive mode in a single run. Method validation was performed according to the criteria of Commission Decision No. 2002/657/EC. The matrix effect and linearity were evaluated. Decision limit (CCα), detection capability (CCβ), accuracy and repeatability of the method are also reported. The proposed method proved to be simple, easy and adequate for high-throughput analysis and was applied to routine analysis by the Brazilian Ministry of Agriculture, Livestock and Food Supply. PMID:27268755

  14. The gatekeeper residue and beyond: homologous calcium-dependent protein kinases as drug development targets for veterinarian Apicomplexa parasites.

    PubMed

    Keyloun, Katelyn R; Reid, Molly C; Choi, Ryan; Song, Yifan; Fox, Anna M W; Hillesland, Heidi K; Zhang, Zhongsheng; Vidadala, Ramasubbarao; Merritt, Ethan A; Lau, Audrey O T; Maly, Dustin J; Fan, Erkang; Barrett, Lynn K; VAN Voorhis, Wesley C; Ojo, Kayode K

    2014-09-01

    Specific roles of individual CDPKs vary, but in general they mediate essential biological functions necessary for parasite survival. A comparative analysis of the structure-activity relationships (SAR) of Neospora caninum, Eimeria tenella and Babesia bovis calcium-dependent protein kinases (CDPKs) together with those of Plasmodium falciparum, Cryptosporidium parvum and Toxoplasma gondii was performed by screening against 333 bumped kinase inhibitors (BKIs). Structural modelling and experimental data revealed that residues other than the gatekeeper influence compound-protein interactions resulting in distinct sensitivity profiles. We subsequently defined potential amino-acid structural influences within the ATP-binding cavity for each orthologue necessary for consideration in the development of broad-spectrum apicomplexan CDPK inhibitors. Although the BKI library was developed for specific inhibition of glycine gatekeeper CDPKs combined with low inhibition of threonine gatekeeper human SRC kinase, some library compounds exhibit activity against serine- or threonine-containing CDPKs. Divergent BKI sensitivity of CDPK homologues could be explained on the basis of differences in the size and orientation of the hydrophobic pocket and specific variation at other amino-acid positions within the ATP-binding cavity. In particular, BbCDPK4 and PfCDPK1 are sensitive to a larger fraction of compounds than EtCDPK1 despite the presence of a threonine gatekeeper in all three CDPKs. PMID:24927073

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

    PubMed Central

    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. PMID:27788228

  16. High-throughput screening of pesticide and veterinary drug residues in baby food by liquid chromatography coupled to quadrupole Orbitrap mass spectrometry.

    PubMed

    Jia, Wei; Chu, Xiaogang; Ling, Yun; Huang, Junrong; Chang, James

    2014-06-20

    A new analytical method was developed and validated for simultaneous analysis of 333 pesticide and veterinary drug residues in baby food. Response surface methodology was employed to optimize a generic extraction method. Ultrahigh-performance liquid chromatography and electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-ESI Q-Orbitrap) was used for the separation and detection of all the analytes. The method was validated by taking into consideration the guidelines specified in Commission Decision 2002/657/EC and SANCO/12571/2013. The extraction recoveries were in a range of 79.8-110.7%, with coefficient of variation <8.3%. The 333 compounds behave dynamic in the range 0.1-1000μgkg(-1) concentration, with correlation coefficient >0.99. The limits of detection for the analytes are in the range 0.01-5.35μgkg(-1). The limits of quantification for the analytes are in the range 0.01-9.27μgkg(-1). This method has been successfully applied on screening of pesticide and veterinary drugs in ninety-three commercial baby food samples, and tilmicosin, fenbendazole, tylosin tartrate and thiabendazole were detected in some samples tested in this study. The present study is very useful for fast screening of different food contaminants.

  17. A simple classification method for residual antibiotics using E. coli cells transformed by the calcium chloride method and drug resistance plasmid DNA.

    PubMed

    Lin, S Y; Kondo, F

    2001-01-01

    Using three different plasmid DNA codings for kanamycin (KM), chloramphenicol (CP), and ampicillin- (AMP) and tetracycline- (TC) resistance, four different competent Escherichia coli strains were transformed by the calcium chloride method to produce KM-, CP- and AMP- and TC-resistant strains. Evaluation of minimum inhibitory concentrations (MIC) of 22 antibiotics, showed KM-resistant E. coli to be cross resistant only to fradiomycin (FRM); CP-resistant E. coli, especially HB101 and JM109 strains, exhibited cross-resistance only to thiamphenicol (TP). On the other hand, AMP- and TC-resistant E. coli showed cross resistance to several penicillins, tetracyclines and erythromycin. E. coli ATCC-27166, the strain most sensitive to all drugs in this experiment, was employed for disc diffusion experiments and from the pattern of appearance of the inhibition zone, eight major antibiotics were divided into three groups depending on their activity against containing each of the three plasmids. Only gentamicin (GM) activity was not affected by any of the drug resistant strains. Assay techniques utilizing three resistant strains may be the technique for screening foods for antibiotic residues in the future.

  18. 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).

    PubMed

    Quirk, Emma; Doggett, Adrian; Bretnall, Alison

    2014-08-01

    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.

  19. Simultaneous detection of antibiotics and other drug residues in the dissolved and particulate phases of water by an off-line SPE combined with on-line SPE-LC-MS/MS: Method development and application.

    PubMed

    Tlili, Ines; Caria, Giovanni; Ouddane, Baghdad; Ghorbel-Abid, Ibtissem; Ternane, Riadh; Trabelsi-Ayadi, Malika; Net, Sopheak

    2016-09-01

    Due to their widespread use in human and animal healthcare, antibiotics and other drug residues are ubiquitous in the aquatic environment. Given their potential impacts on ecosystem functioning and public health, the quantification of environmental drug residues has become a necessity. Various analysis techniques have been found to be suitable for reliable detection of such compounds. However, quantification can be difficult because these compounds are present at trace or ultra-trace levels. Consequently, the accuracy of environmental analyses depends on both the efficiency and the robustness of the extraction and quantification method. In this work, an off-line solid-phase extraction (SPE) combined with on-line SPE-LC-MS/MS was applied to the simultaneous extraction and quantification of 26 pharmaceutical products, including 18 antibiotics, dissolved in a water phase. Optimal conditions were determined and then applied to assess the contamination level of the targeted drug residues in water collected from four sites in Northern France: a river, the input and output of an aerated lagoon, and a wastewater treatment plant. Drug residues associated with suspended solid matter (SSM) were also quantified in this work using pressurized liquid extraction (PLE) combined with an on-line SPE-LC-MS/MS system in order to complete an assessment of the degree of total background pollution.

  20. Simultaneous detection of antibiotics and other drug residues in the dissolved and particulate phases of water by an off-line SPE combined with on-line SPE-LC-MS/MS: Method development and application.

    PubMed

    Tlili, Ines; Caria, Giovanni; Ouddane, Baghdad; Ghorbel-Abid, Ibtissem; Ternane, Riadh; Trabelsi-Ayadi, Malika; Net, Sopheak

    2016-09-01

    Due to their widespread use in human and animal healthcare, antibiotics and other drug residues are ubiquitous in the aquatic environment. Given their potential impacts on ecosystem functioning and public health, the quantification of environmental drug residues has become a necessity. Various analysis techniques have been found to be suitable for reliable detection of such compounds. However, quantification can be difficult because these compounds are present at trace or ultra-trace levels. Consequently, the accuracy of environmental analyses depends on both the efficiency and the robustness of the extraction and quantification method. In this work, an off-line solid-phase extraction (SPE) combined with on-line SPE-LC-MS/MS was applied to the simultaneous extraction and quantification of 26 pharmaceutical products, including 18 antibiotics, dissolved in a water phase. Optimal conditions were determined and then applied to assess the contamination level of the targeted drug residues in water collected from four sites in Northern France: a river, the input and output of an aerated lagoon, and a wastewater treatment plant. Drug residues associated with suspended solid matter (SSM) were also quantified in this work using pressurized liquid extraction (PLE) combined with an on-line SPE-LC-MS/MS system in order to complete an assessment of the degree of total background pollution. PMID:27151499

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

    PubMed

    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.

  2. Wide-scope analysis of veterinary drug and pesticide residues in animal feed by liquid chromatography coupled to quadrupole-time-of-flight mass spectrometry.

    PubMed

    Aguilera-Luiz, María M; Romero-González, Roberto; Plaza-Bolaños, Patricia; Martínez Vidal, José Luis; Garrido Frenich, Antonia

    2013-08-01

    A fast and generic method has been developed for the simultaneous monitoring of >250 pesticides and veterinary drugs (VDs) in animal feed. A 'dilute-and-shoot' extraction with water and acetonitrile (1% formic acid) followed by a clean-up step with Florisil cartridges was applied. The extracts were analysed by ultra-high performance liquid chromatography coupled to hybrid analyser quadrupole-time-of-flight mass spectrometry using both positive and negative electrospray ionisation. The detection of the residues was accomplished by retention time and accurate mass using an in-house database. The identification of the detected compounds was carried out by searching of fragment ions for each compound and isotopic pattern. The optimised method was validated and recoveries ranged from 60% to 120% at three concentrations (10, 50 and 100 μg kg(-1)) for 30%, 68% and 80% of compounds, respectively, included in the database (364) in chicken feed. Document SANCO 12495/2011 and Directive 2002/657/CE were used as guidelines for method validation. Intra-day and inter-day precisions, expressed as relative standard deviations, were lower than 20% for more than 90% of compounds. The limits of quantification ranged from 4 to 200 μg kg(-1) for most analytes, which are sufficient to verify compliance of products with legal tolerances. The applicability of the procedure was further tested on different types of feed (chicken, hen, rabbit and horse feed), evaluating recoveries and repeatability. Finally, the method was applied to the analysis of 18 feed samples, detecting some VDs (sulfadiazine, trimethoprim, robenidin and monensin Na) and only one pesticide (chlorpyrifos). PMID:23712649

  3. Development and validation of a streamlined method designed to detect residues of 62 veterinary drugs in bovine kidney using ultra-high performance liquid chromatography--tandem mass spectrometry.

    PubMed

    Lehotay, Steven J; Lightfield, Alan R; Geis-Asteggiante, Lucía; Schneider, Marilyn J; Dutko, Terry; Ng, Chilton; Bluhm, Louis; Mastovska, Katerina

    2012-08-01

    In the USA, the US Department of Agriculture's Food Safety and Inspection Service (FSIS) conducts the National Residue Program designed to monitor veterinary drug and other chemical residues in beef and other slaughtered food animals. Currently, FSIS uses a 7-plate bioassay in the laboratory to screen for antimicrobial drugs in bovine kidneys from those animals tested positive by inspectors in the slaughter establishments. The microbial inhibition bioassay has several limitations in terms of monitoring scope, sensitivity, selectivity, and analysis time. Ultra-high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS) has many advantages over the bioassay for this application, and this study was designed to develop, evaluate, and validate a fast UHPLC-MS/MS method for antibiotics and other high-priority veterinary drugs in bovine kidney. Five existing multi-class, multi-residue methods from the literature were tested and compared, and each performed similarly. Experiments with incurred samples demonstrated that a 5-min shake of 2 g homogenized kidney with 10 ml of 4/1 (v/v) acetonitrile/water followed by simultaneous clean-up of the initial extract with 0.5 g C18 and 10 ml hexane gave a fast, simple, and effective sample preparation method for the <10 min UHPLC-MS/MS analysis. An extensive 5-day validation process demonstrated that the final method could be used to acceptably screen for 54 of the 62 drugs tested, and 50 of those met qualitative MS identification criteria. Quantification was not needed in the application, but the method gave ≥ 70% recoveries and ≤ 25% reproducibilities for 30 of the drugs. PMID:22851364

  4. 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.

    PubMed

    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

  5. 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.

    PubMed

    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.

  6. 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.

    PubMed

    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. PMID:27412322

  7. A long hangover from party drugs: residual proteomic changes in the hippocampus of rats 8 weeks after γ-hydroxybutyrate (GHB), 3,4-methylenedioxymethamphetamine (MDMA) or their combination.

    PubMed

    van Nieuwenhuijzen, Petra S; Kashem, Mohammed A; Matsumoto, Izuru; Hunt, Glenn E; McGregor, Iain S

    2010-07-01

    3,4-Methylenedioxymethamphetamine (MDMA) and gamma-hydroxybutyrate (GHB) are popular party drugs that are used for their euphoric and prosocial effects, and sometimes in combination. Both drugs increase markers of oxidative stress in the hippocampus and can cause lasting impairments in hippocampal-dependent forms of memory. To gain further information on the biochemical mechanisms underlying these effects, the current study examined residual changes in hippocampal protein expression measured 8 weeks after chronic administration of GHB (500mg/kg), MDMA (5mg/kg) or their combination (GHB/MDMA). The drugs were administered once a day for 10 days in an environment with an elevated ambient temperature of 28 degrees C. Results showed significant changes in protein expression, relative to controls, in all three groups: MDMA and GHB given alone caused residual changes in 8 and 5 proteins respectively, while the GHB/MDMA combination significantly changed 6 proteins. The altered proteins had roles in neuroplasticity, neuroprotection, intracellular signalling and cytoskeletal function. The largest change (-4.3-fold) was seen in the MDMA group with the protein C-crk: a protein implicated in learning-related neuroplasticity. The second largest change (3.0-fold) was seen in the GHB group in Glutathione-S-transferase (GST), a protein that protects against oxidative stress. Two cytoskeletal proteins (Tubulin Folding Cofactor B and Tropomyosin-alpha-3 chain) and one plasticity related protein (Neuronal Pentraxin-1 NP1) were similarly changed in both the MDMA and the GHB groups, while two intracellular signalling proteins (alpha-soluble NSF-attachment protein and subunits of the V-type proton ATPase) were changed in both the MDMA/GHB and the MDMA groups. These results provide some insight into the molecular pathways possibly underlying the lasting cognitive deficits arising from GHB and/or MDMA use.

  8. Single-stranded oligonucleotide adducts formed by Pt complexes favoring left-handed base canting: steric effect of flanking residues and relevance to DNA adducts formed by Pt anticancer drugs.

    PubMed

    Saad, Jamil S; Marzilli, Patricia A; Intini, Francesco P; Natile, Giovanni; Marzilli, Luigi G

    2011-09-01

    Platinum anticancer drug binding to DNA creates large distortions in the cross-link (G*G*) and the adjacent XG* base pair (bp) steps (G* = N7-platinated G). These distortions, which are responsible for anticancer activity, depend on features of the duplex (e.g., base pairing) and of the cross-link moiety (e.g., the position and canting of the G* bases). The duplex structure stabilizes the head-to-head (HH) over the head-to-tail (HT) orientation and right-handed (R) over left-handed (L) canting of the G* bases. To provide fundamental chemical information relevant to the assessment of such duplex effects, we examine (S,R,R,S)-BipPt(oligo) adducts (Bip = 2,2'-bipiperidine with S,R,R,S chiral centers at the N, C, C, and N chelate ring atoms, respectively; oligo = d(G*pG*) with 3'- and/or 5'-substituents). The moderately bulky (S,R,R,S)-Bip ligand favors L canting and slows rotation about the Pt-G* bonds, and the (S,R,R,S)-BipPt(oligo) models provide more useful data than do dynamic models derived from active Pt drugs. All 5'-substituents in (S,R,R,S)-BipPt(oligo) adducts favor the normal HH conformer (∼97%) by destabilizing the HT conformer through clashes with the 3'-G* residue rather than through favorable H-bonding interactions with the carrier ligand in the HH conformer. For all (S,R,R,S)-BipPt(oligo) adducts, the S pucker of the 5'-X residue is retained. For these adducts, a 5'-substituent had only modest effects on the degree of L canting for the (S,R,R,S)-BipPt(oligo) HH conformer. This small flanking 5'-substituent effect on an L-canted HH conformer contrasts with the significant decrease in the degree of R canting previously observed for flanking 5'-substituents in the R-canted (R,S,S,R)-BipPt(oligo) analogues. The present data support our earlier hypothesis that the distortion distinctive to the XG* bp step (S to N pucker change and movement of the X residue) is required for normal stacking and X·X' WC H bonding and to prevent XG* residue clashes.

  9. Determination of Residual Nonsteroidal Anti-Inflammatory Drugs in Aqueous Sample Using Magnetic Nanoparticles Modified with Cetyltrimethylammonium Bromide by High Performance Liquid Chromatography

    PubMed Central

    Khoeini Sharifabadi, Malihe; Saber-Tehrani, Mohammad; Waqif Husain, Syed; Mehdinia, Ali; Aberoomand-Azar, Parviz

    2014-01-01

    A simple and sensitive solid-phase extraction method for separation and preconcentration of trace amount of four nonsteroidal anti-inflammatory drugs (naproxen, indomethacin, diclofenac, and ibuprofen) using Fe3O4 magnetic nanoparticles modified with cetyltrimethylammonium bromide has been developed. For this purpose, the surface of MNPs was modified with cetyltrimethylammonium bromide (CTAB) as a cationic surfactant. Effects of different parameters influencing the extraction efficiency of drugs including the pH, amount of salt, shaking time, eluent type, the volume of solvent, amount of adsorbent, sample volume, and the time of desorption were investigated and optimized. Methanol has been used as desorption solvent and the extracts were analysed on a reversed-phase octadecyl silica column using 0.02 M phosphate-buffer (pH = 6.02) acetonitrile (65 : 35 v/v) as the mobile phase and the effluents were measured at 202 nm with ultraviolet detector. The relative standard deviation (RSD%) of the method was investigated at three concentrations (25, 50, and 200 ng/mL) and was in the range of 3.98–9.83% (n = 6) for 50 ng/mL. The calibration curves obtained for studied drugs show reasonable linearity (R2 > 0.99) and the limit of detection (LODs) ranged between 2 and 7 ng/mL. Finally, the proposed method has been effectively employed in extraction and determination of the drugs in biological and environmental samples. PMID:24982923

  10. [Multi-residue determination of veterinary drugs in cheese by QuEChERS and liquid chromatography-tandem mass spectrometry].

    PubMed

    Cao, Yafei; Kang, Jian; Chang, Qiaoying; Hu, Xueyan; Wang, Zhibin; Fan, Chunlin; Wang, Minglin

    2015-02-01

    A rapid and sensitive method has been developed for the simultaneous determination of 50 veterinary drugs (including macrolides, quinolones, sulfonamides, and tetracyclines) in cheese using a modified QuEChERS method coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). After adding Na2EDTA buffer solution and ceramic homogenizer, the cheese sample was extracted by 5% (v/v) acetic acid-acetonitrile, sodium chloride and anhydrous sodium sulfate were used for salting-out process. The resulting supernatant solution was purified by C18 sorbent and the re-dissolved solution was analyzed by LC-MS/MS under dynamic multi-reaction monitoring (dynamic MRM) mode via positive electrospray ionization with a ZORBAX-SB-C18 column. The limits of quantification (LOQ, S/N= 10) of the target compounds ranged from 0. 05 µg/kg to 20 µg/kg in cheese. At spiked levels of 20, 50, 100 µg/kg (n =6) , the percentages of drug with a recovery between 70% and 120% were 94%, 92%, and 96%, respectively. The relative standard deviations (RSDs) were between 1% and 14%. This method has been applied to determine seven real samples from markets. Roxithromycin and flumequine have been detected in two samples separately. The results demonstrated that this simple, rapid and accurate method is suitable for the detection of multi-class veterinary drugs in cheese.

  11. Multi-class, multi-residue analysis of trace veterinary drugs in milk by rapid screening and quantification using ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

    PubMed

    Zhang, Yaqian; Li, Xiang; Liu, Xiaomao; Zhang, Jinjie; Cao, Yanzhong; Shi, Zhihong; Sun, Hanwen

    2015-12-01

    A simple and rapid multi-class multi-residue analytical method was developed for the screening and quantification of veterinary drugs in milk by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). A total of 90 veterinary drugs investigated belonged to almost 20 classes including lincomycins, macrolides, sulfonamides, quinolones, tetracyclines, β-agonists, β-lactams, sedatives, β-receptor antagonists, sex hormones, glucocorticoids, nitroimidazoles, benzimidazoles, nitrofurans, and some others. A modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) procedure was developed for the sample preparation without the solid-phase extraction step. The linearity, sensitivity, accuracy, repeatability, and reproducibility of the method were fully validated. The response of the detector was linear for each target compound in a wide concentration range with a correlation coefficient (R(2)) of 0.9973 to 0.9999 (among them R(2)>0.999 for 73 of 90 analytes). The range of the limit of quantification for these compounds in the milk ranged from 0.10 to 17.30μg/kg. The repeatability and reproducibility were in the range of 2.11 to 9.62% and 2.76 to 13.9%, respectively. The average recoveries ranged from 72.62 to 122.2% with the RSD (n=6) of 1.30 to 9.61% at 3 concentration levels. For the screening method, the data of the precursor and product ions of the target analytes were simultaneously acquired under the all ions MS/MS mode in a single run. An accurate mass database for the confirmation and identification of the target compounds was established. The applicability of the screening method was verified by applying to real milk samples. The proposed analytical method allows the identification and confirmation of the target veterinary drugs at trace levels employing quick analysis time. Certain veterinary drugs were detected in some cases.

  12. Validation and uncertainties evaluation of an isotope dilution-SPE-LC-MS/MS for the quantification of drug residues in surface waters.

    PubMed

    Brieudes, V; Lardy-Fontan, S; Lalere, B; Vaslin-Reimann, S; Budzinski, H

    2016-01-01

    The present work describes the development and validation of a reference method conducted at the French National Institute of Metrology (LNE) for the quantitative determination of psychoactive compounds in the dissolved fraction of surface waters. More specifically an isotope dilution-SPE-LC-MS/MS based method has been implemented for the characterization of a broad range of analytes belonging to different classes of psychotropic drugs such as benzodiazepines, antidepressants, stimulants, opiates and opioids, anticonvulsants, anti-dementia drugs, analgesics as well as the anti-inflammatory drug diclofenac in the low ng L(-1) range of concentration. Full validation of the method was performed following procedures described by the French standard NF T90-210. Limits of quantification between 0.14 and 3.54 ng L(-1) were obtained. Method recoveries from 71 to 123% were observed with standard deviation below 10% in intermediate precision conditions. Accuracy was determined for every compound: measurement errors were between -4 and +1% and standard deviations in intermediate precision conditions were included within a 1-9% interval. Finally, measurement uncertainties were evaluated following the Guide to the expression of uncertainty in measurement (GUM). Expanded uncertainties (k=2) ranged from 2% for carbamazepine, EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) and venlafaxine to 17% for diazepam. The validated method was implemented to Seine river surface waters demonstrating its fitness for purpose. All compounds were detected and 22 out of 25 analytes were quantified. More specifically, measured concentration ranged from 0.39 ng L(-1) for MDMA (3,4-methylene-dioxy-N-methylamphetamine) to 182 ng L(-1) for gabapentine.

  13. Validation and uncertainties evaluation of an isotope dilution-SPE-LC-MS/MS for the quantification of drug residues in surface waters.

    PubMed

    Brieudes, V; Lardy-Fontan, S; Lalere, B; Vaslin-Reimann, S; Budzinski, H

    2016-01-01

    The present work describes the development and validation of a reference method conducted at the French National Institute of Metrology (LNE) for the quantitative determination of psychoactive compounds in the dissolved fraction of surface waters. More specifically an isotope dilution-SPE-LC-MS/MS based method has been implemented for the characterization of a broad range of analytes belonging to different classes of psychotropic drugs such as benzodiazepines, antidepressants, stimulants, opiates and opioids, anticonvulsants, anti-dementia drugs, analgesics as well as the anti-inflammatory drug diclofenac in the low ng L(-1) range of concentration. Full validation of the method was performed following procedures described by the French standard NF T90-210. Limits of quantification between 0.14 and 3.54 ng L(-1) were obtained. Method recoveries from 71 to 123% were observed with standard deviation below 10% in intermediate precision conditions. Accuracy was determined for every compound: measurement errors were between -4 and +1% and standard deviations in intermediate precision conditions were included within a 1-9% interval. Finally, measurement uncertainties were evaluated following the Guide to the expression of uncertainty in measurement (GUM). Expanded uncertainties (k=2) ranged from 2% for carbamazepine, EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine) and venlafaxine to 17% for diazepam. The validated method was implemented to Seine river surface waters demonstrating its fitness for purpose. All compounds were detected and 22 out of 25 analytes were quantified. More specifically, measured concentration ranged from 0.39 ng L(-1) for MDMA (3,4-methylene-dioxy-N-methylamphetamine) to 182 ng L(-1) for gabapentine. PMID:26695245

  14. Mutation of G234 amino acid residue in Candida albicans drug-resistance-related protein Rta2p is associated with fluconazole resistance and dihydrosphingosine transport

    PubMed Central

    Zhang, Shi-Qun; Miao, Qi; Li, Li-Ping; Zhang, Lu-lu; Yan, Lan; Jia, Yu; Cao, Yong-Bing; Jiang, Yuan-Ying

    2015-01-01

    Widespread and repeated use of azoles has led to the rapid development of drug resistance in Candida albicans. Our previous study found Rta2p, a membrane protein with 7 transmembrane domains, was involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans. Conserved amino acids in the transmembrane domain of Rta2p were subjected to site-directed mutagenesis. The sensitivity of C. albicans to fluconazole in vitro was examined by minimum inhibitory concentration and killing assay, and the therapeutic efficacy of fluconazole in vivo was performed by systemic mice candidiasis model. Furthermore, dihydrosphingosine transport activity was detected by NBD labeled D-erythro-dihydrosphingosine uptake and release assay, and the sensitivity to sphingolipid biosynthesis inhibitors. We successfully constructed 14 mutant strains of Rta2p, screened them by minimum inhibitory concentration and found Ca2+ did not completely induce fluconazole resistance with G158E and G234S mutations. Furthermore, we confirmed that G234S mutant enhanced the therapeutic efficacy of fluconazole against systemic candidiasis and significantly increased the accumulation of dihydrosphingosine by decreasing its release. However, G158E mutant didn't affect drug therapeutic efficacy in vivo and dihydrosphingosine transport in C. albicans. G234 of Rta2p in C. albicans is crucial in calcineurin-mediated fluconazole resistance and dihydrosphingosine transport. PMID:26220356

  15. Mutation of G234 amino acid residue in candida albicans drug-resistance-related protein Rta2p is associated with fluconazole resistance and dihydrosphingosine transport.

    PubMed

    Zhang, Shi-Qun; Miao, Qi; Li, Li-Ping; Zhang, Lu-Lu; Yan, Lan; Jia, Yu; Cao, Yong-Bing; Jiang, Yuan-Ying

    2015-01-01

    Widespread and repeated use of azoles has led to the rapid development of drug resistance in Candida albicans. Our previous study found Rta2p, a membrane protein with 7 transmembrane domains, was involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans. Conserved amino acids in the transmembrane domain of Rta2p were subjected to site-directed mutagenesis. The sensitivity of C. albicans to fluconazole in vitro was examined by minimum inhibitory concentration and killing assay, and the therapeutic efficacy of fluconazole in vivo was performed by systemic mice candidiasis model. Furthermore, dihydrosphingosine transport activity was detected by NBD labeled D-erythro-dihydrosphingosine uptake and release assay, and the sensitivity to sphingolipid biosynthesis inhibitors. We successfully constructed 14 mutant strains of Rta2p, screened them by minimum inhibitory concentration and found Ca(2+) did not completely induce fluconazole resistance with G158E and G234S mutations. Furthermore, we confirmed that G234S mutant enhanced the therapeutic efficacy of fluconazole against systemic candidiasis and significantly increased the accumulation of dihydrosphingosine by decreasing its release. However, G158E mutant didn't affect drug therapeutic efficacy in vivo and dihydrosphingosine transport in C. albicans. G234 of Rta2p in C. albicans is crucial in calcineurin-mediated fluconazole resistance and dihydrosphingosine transport.

  16. Mutation of G234 amino acid residue in candida albicans drug-resistance-related protein Rta2p is associated with fluconazole resistance and dihydrosphingosine transport.

    PubMed

    Zhang, Shi-Qun; Miao, Qi; Li, Li-Ping; Zhang, Lu-Lu; Yan, Lan; Jia, Yu; Cao, Yong-Bing; Jiang, Yuan-Ying

    2015-01-01

    Widespread and repeated use of azoles has led to the rapid development of drug resistance in Candida albicans. Our previous study found Rta2p, a membrane protein with 7 transmembrane domains, was involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans. Conserved amino acids in the transmembrane domain of Rta2p were subjected to site-directed mutagenesis. The sensitivity of C. albicans to fluconazole in vitro was examined by minimum inhibitory concentration and killing assay, and the therapeutic efficacy of fluconazole in vivo was performed by systemic mice candidiasis model. Furthermore, dihydrosphingosine transport activity was detected by NBD labeled D-erythro-dihydrosphingosine uptake and release assay, and the sensitivity to sphingolipid biosynthesis inhibitors. We successfully constructed 14 mutant strains of Rta2p, screened them by minimum inhibitory concentration and found Ca(2+) did not completely induce fluconazole resistance with G158E and G234S mutations. Furthermore, we confirmed that G234S mutant enhanced the therapeutic efficacy of fluconazole against systemic candidiasis and significantly increased the accumulation of dihydrosphingosine by decreasing its release. However, G158E mutant didn't affect drug therapeutic efficacy in vivo and dihydrosphingosine transport in C. albicans. G234 of Rta2p in C. albicans is crucial in calcineurin-mediated fluconazole resistance and dihydrosphingosine transport. PMID:26220356

  17. Multi-class method for determination of veterinary drug residues and other contaminants in infant formula by ultra performance liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhan, Jia; Zhong, Ying-ying; Yu, Xue-jun; Peng, Jin-feng; Chen, Shubing; Yin, Ju-yi; Zhang, Jia-Jie; Zhu, Yan

    2013-06-01

    A rapid, simple and generic analytical method which was able to simultaneously determine 220 undesirable chemical residues in infant formula had been developed. The method comprised of extraction with acetonitrile, clean-up by low temperature and water precipitation, and analysis by ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS-MS) using multiple reaction monitoring (MRM) mode. Most fat materials in acetonitrile extract were eliminated by low temperature clean-up. The water precipitation, providing a necessary and supplementary cleanup, could avoid losses of hydrophobic analytes (avermectins, ionophores). Average recoveries for spiked infant formula were in the range from 57% to 147% with associated RSD values between 1% and 28%. For over 80% of the analytes, the recoveries were between 70% and 120% with RSD values in the range of 1-15%. The limits of quantification (LOQs) were from 0.01 to 5 μg/kg, which were usually sufficient to verify the compliance of products with legal tolerances. Application of this method in routine monitoring programs would imply a drastic reduction of both effort and time. PMID:23411184

  18. Improved Cross Validation of a Static Ubiquitin Structure Derived from High Precision Residual Dipolar Couplings Measured in a Drug-Based Liquid Crystalline Phase

    PubMed Central

    2014-01-01

    The antibiotic squalamine forms a lyotropic liquid crystal at very low concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of temperature (1-40 °C) and pH (4-8). Squalamine is positively charged, and comparison of the alignment of ubiquitin relative to 36 previously reported alignment conditions shows that it differs substantially from most of these, but is closest to liquid crystalline cetyl pyridinium bromide. High precision residual dipolar couplings (RDCs) measured for the backbone 1H-15N, 15N-13C′, 1Hα-13Cα, and 13C′-13Cα one-bond interactions in the squalamine medium fit well to the static structural model previously derived from NMR data. Inclusion into the structure refinement procedure of these RDCs, together with 1H-15N and 1Hα-13Cα RDCs newly measured in Pf1, results in improved agreement between alignment-induced changes in 13C′ chemical shift, 3JHNHα values, and 13Cα-13Cβ RDCs and corresponding values predicted by the structure, thereby validating the high quality of the single-conformer structural model. This result indicates that fitting of a single model to experimental data provides a better description of the average conformation than does averaging over previously reported NMR-derived ensemble representations. The latter can capture dynamic aspects of a protein, thus making the two representations valuable complements to one another. PMID:24568736

  19. A combined liquid chromatography-triple-quadrupole mass spectrometry method for the residual detection of veterinary drugs in porcine muscle, milk, and eggs.

    PubMed

    Zhang, Dan; Park, Zee-Yong; Park, Jin-A; Kim, Seong-Kwan; Jeong, Daun; Cho, Sang-Hyun; Shim, Jae-Han; Kim, Jin-Suk; Abd El-Aty, A M; Shin, Ho-Chul

    2016-06-01

    A liquid chromatography-electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) method was developed for monitoring and detection of four different drugs, namely acetanilide, pentylenetetrazole, phenacetin, and tetramethrin in porcine muscle, pasteurized milk, and table egg samples. For acetanilide and pentylenetetrazole, the samples were extracted with 0.1 % formic acid in acetonitrile, followed by defatting with n-hexane, partitioning at -20 °C for 1 h, centrifugation, and filtration, whereas the quick, easy, cheap, effective, rugged, and safe "QuEChERS" method was used for phenacetin and tetramethrin. The final extracts were combined and analyzed in a single chromatographic run using an XBridge(TM) analytical column and 0.1 % formic acid and 10 mM ammonium formate in ultrapure water (A) and 0.1 % formic acid and 10 mM ammonium formate in methanol (B) as the mobile phase. Owing to the unavailability of internal standards, matrix-matched calibrations were used for analyte quantification with coefficients of determination (R (2)) ≥ 0.9865. The intra- and inter-day accuracies ranged from 60.75 to 90.90 % and from 63.75 to 89.30 %, respectively, while the respective analytical precisions were 1.48-17.44 % (23.3 % for porcine sample spiked with phenacetin) and 1.97-15.78 %. The limits of quantification (LOQ) were between 0.5 and 2.5 ng/g in the matrices tested. Food samples purchased from local markets in Seoul were analyzed using the developed method and none of the tested drugs was detected. PMID:27178050

  20. Rapid determination of 88 veterinary drug residues in milk using automated TurborFlow online clean-up mode coupled to liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhu, Wei-xia; Yang, Ji-zhou; Wang, Zhao-xing; Wang, Cai-juan; Liu, Ya-feng; Zhang, Li

    2016-02-01

    A novel method based on TurborFlow online solid phase extraction (SPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been established for simultaneous screening and confirmation of 88 wide-range veterinary drugs belonging to eight families (20 sulfonamides, 7 macrolides, 15 quinolones, 8 penicillins, 13 benzimidazoles, 4 tetracyclines, 2 sedatives, and 19 hormones) in milk. The preparation method consists of sample dilution and ultrasonic extraction, followed by an automated turbulent flow cyclone chromatography sample clean-up system. The detection was achieved in selected reaction monitoring mode (SRM). The total run time was within 39 min, including automated extraction, analytical chromatography and re-equilibration of the turboflow system. The optimization of different experimental parameters including extraction, purification, separation, and detection were evaluated separately in this study. The developed method was validated and good performing characteristics were obtained. The linear regression coefficients (R(2)) of matrix-match calibration standard curves established for quantification were higher than 0.9930. The limits of detection (LOD) were in the range of 0.2-2.0 μg/kg given by signal-noise ratio ≥3 (S/N) and the limits of quantification (LOQ, S/N≥10) ranged between 0.5 μg/kg and 10 μg/kg. Average recoveries of spiked target compounds with different levels were between 63.1% and 117.4%, with percentage relative standard deviations (RSD) in the range of 3.3-17.6%. The results indicated that the developed method has great potential for the routine laboratory analysis of large numbers of samples on measuring different classes of compounds. In comparison to traditional procedures, the automated sample clean-up ensures rapid, effective, sensitive analyses of veterinary drugs in milk.

  1. Improved cross validation of a static ubiquitin structure derived from high precision residual dipolar couplings measured in a drug-based liquid crystalline phase.

    PubMed

    Maltsev, Alexander S; Grishaev, Alexander; Roche, Julien; Zasloff, Michael; Bax, Ad

    2014-03-12

    The antibiotic squalamine forms a lyotropic liquid crystal at very low concentrations in water (0.3-3.5% w/v), which remains stable over a wide range of temperature (1-40 °C) and pH (4-8). Squalamine is positively charged, and comparison of the alignment of ubiquitin relative to 36 previously reported alignment conditions shows that it differs substantially from most of these, but is closest to liquid crystalline cetyl pyridinium bromide. High precision residual dipolar couplings (RDCs) measured for the backbone (1)H-(15)N, (15)N-(13)C', (1)H(α)-(13)C(α), and (13)C'-(13)C(α) one-bond interactions in the squalamine medium fit well to the static structural model previously derived from NMR data. Inclusion into the structure refinement procedure of these RDCs, together with (1)H-(15)N and (1)H(α)-(13)C(α) RDCs newly measured in Pf1, results in improved agreement between alignment-induced changes in (13)C' chemical shift, (3)JHNHα values, and (13)C(α)-(13)C(β) RDCs and corresponding values predicted by the structure, thereby validating the high quality of the single-conformer structural model. This result indicates that fitting of a single model to experimental data provides a better description of the average conformation than does averaging over previously reported NMR-derived ensemble representations. The latter can capture dynamic aspects of a protein, thus making the two representations valuable complements to one another. PMID:24568736

  2. Impact of Hemoglobin A1c Levels on Residual Platelet Reactivity and Outcomes After Insertion of Coronary Drug-Eluting Stents (from the ADAPT-DES Study).

    PubMed

    Schoos, Mikkel M; Dangas, George D; Mehran, Roxana; Kirtane, Ajay J; Yu, Jennifer; Litherland, Claire; Clemmensen, Peter; Stuckey, Thomas D; Witzenbichler, Bernhard; Weisz, Giora; Rinaldi, Michael J; Neumann, Franz-Josef; Metzger, D Christopher; Henry, Timothy D; Cox, David A; Duffy, Peter L; Brodie, Bruce R; Mazzaferri, Ernest L; Maehara, Akiko; Stone, Gregg W

    2016-01-15

    An increasing hemoglobin A1c (HbA1c) level portends an adverse cardiovascular prognosis; however, the association between glycemic control, platelet reactivity, and outcomes after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is unknown. We sought to investigate whether HbA1c levels are associated with high platelet reactivity (HPR) in patients loaded with clopidogrel and aspirin, thereby constituting an argument for intensified antiplatelet therapy in patients with poor glycemic control. In the prospective, multicenter Assessment of Dual Antiplatelet Therapy With Drug Eluting Stents registry, HbA1c levels were measured as clinically indicated in 1,145 of 8,582 patients, stratified by HbA1c <6.5% (n = 551, 48.12%), 6.5% to 8.5% (n = 423, 36.9%), and >8.5% (n = 171, 14.9%). HPR on clopidogrel and aspirin was defined after PCI as P2Y12 reaction units (PRU) >208 and aspirin reaction units >550, respectively. HPR on clopidogrel was frequent (48.3%), whereas HPR on aspirin was not (3.9%). Patients with HbA1c >8.5% were younger, more likely non-Caucasian, had a greater body mass index, and more insulin-treated diabetes and acute coronary syndromes. Proportions of PRU >208 (42.5%, 50.2%, and 62.3%, p <0.001) and rates of definite or probable stent thrombosis (ST; 0.9%, 2.7%, and 4.2%, p = 0.02) increased progressively with HbA1c groups. Clinically relevant bleeding was greatest in the intermediate HbA1c group (8.2% vs 13.1% vs 9.5%, p = 0.04). In adjusted models that included PRU, high HbA1c levels (>8.5) remained associated with ST (hazard ratio 3.92, 95% CI 1.29 to 12.66, p = 0.02) and cardiac death (hazard ratio 4.24, 95% CI 1.41 to 12.70) but not bleeding at 2-year follow-up. There was no association between aspirin reaction units >550 and HbA1c levels. In conclusion, in this large-scale study, HbA1c and HPR were positively associated, but the clinical effect on adverse outcome was driven by poor glycemic control, which predicted ST and

  3. 40 CFR 161.240 - Residue chemistry data requirements.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... requirement if their residues are regulated by the Food and Drug Administration at 21 CFR 178.1010. (11... metabolism in livestock are required when residues occur on a livestock feed, or the pesticide is to...

  4. 40 CFR 161.240 - Residue chemistry data requirements.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... requirement if their residues are regulated by the Food and Drug Administration at 21 CFR 178.1010. (11... metabolism in livestock are required when residues occur on a livestock feed, or the pesticide is to...

  5. 40 CFR 161.240 - Residue chemistry data requirements.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... requirement if their residues are regulated by the Food and Drug Administration at 21 CFR 178.1010. (11... metabolism in livestock are required when residues occur on a livestock feed, or the pesticide is to...

  6. A critical assessment of the performance criteria in confirmatory analysis for veterinary drug residue analysis using mass spectrometric detection in selected reaction monitoring mode.

    PubMed

    Berendsen, Bjorn J A; Meijer, Thijs; Wegh, Robin; Mol, Hans G J; Smyth, Wesley G; Armstrong Hewitt, S; van Ginkel, Leen; Nielen, Michel W F

    2016-05-01

    Besides the identification point system to assure adequate set-up of instrumentation, European Commission Decision 2002/657/EC includes performance criteria regarding relative ion abundances in mass spectrometry and chromatographic retention time. In confirmatory analysis, the relative abundance of two product ions, acquired in selected reaction monitoring mode, the ion ratio should be within certain ranges for confirmation of the identity of a substance. The acceptable tolerance of the ion ratio varies with the relative abundance of the two product ions and for retention time, CD 2002/657/EC allows a tolerance of 5%. Because of rapid technical advances in analytical instruments and new approaches applied in the field of contaminant testing in food products (multi-compound and multi-class methods) a critical assessment of these criteria is justified. In this study a large number of representative, though challenging sample extracts were prepared, including muscle, urine, milk and liver, spiked with 100 registered and banned veterinary drugs at levels ranging from 0.5 to 100 µg/kg. These extracts were analysed using SRM mode using different chromatographic conditions and mass spectrometers from different vendors. In the initial study, robust data was collected using four different instrumental set-ups. Based on a unique and highly relevant data set, consisting of over 39 000 data points, the ion ratio and retention time criteria for applicability in confirmatory analysis were assessed. The outcomes were verified based on a collaborative trial including laboratories from all over the world. It was concluded that the ion ratio deviation is not related to the value of the ion ratio, but rather to the intensity of the lowest product ion. Therefore a fixed ion ratio deviation tolerance of 50% (relative) is proposed, which also is applicable for compounds present at sub-ppb levels or having poor ionisation efficiency. Furthermore, it was observed that retention time

  7. A critical assessment of the performance criteria in confirmatory analysis for veterinary drug residue analysis using mass spectrometric detection in selected reaction monitoring mode.

    PubMed

    Berendsen, Bjorn J A; Meijer, Thijs; Wegh, Robin; Mol, Hans G J; Smyth, Wesley G; Armstrong Hewitt, S; van Ginkel, Leen; Nielen, Michel W F

    2016-05-01

    Besides the identification point system to assure adequate set-up of instrumentation, European Commission Decision 2002/657/EC includes performance criteria regarding relative ion abundances in mass spectrometry and chromatographic retention time. In confirmatory analysis, the relative abundance of two product ions, acquired in selected reaction monitoring mode, the ion ratio should be within certain ranges for confirmation of the identity of a substance. The acceptable tolerance of the ion ratio varies with the relative abundance of the two product ions and for retention time, CD 2002/657/EC allows a tolerance of 5%. Because of rapid technical advances in analytical instruments and new approaches applied in the field of contaminant testing in food products (multi-compound and multi-class methods) a critical assessment of these criteria is justified. In this study a large number of representative, though challenging sample extracts were prepared, including muscle, urine, milk and liver, spiked with 100 registered and banned veterinary drugs at levels ranging from 0.5 to 100 µg/kg. These extracts were analysed using SRM mode using different chromatographic conditions and mass spectrometers from different vendors. In the initial study, robust data was collected using four different instrumental set-ups. Based on a unique and highly relevant data set, consisting of over 39 000 data points, the ion ratio and retention time criteria for applicability in confirmatory analysis were assessed. The outcomes were verified based on a collaborative trial including laboratories from all over the world. It was concluded that the ion ratio deviation is not related to the value of the ion ratio, but rather to the intensity of the lowest product ion. Therefore a fixed ion ratio deviation tolerance of 50% (relative) is proposed, which also is applicable for compounds present at sub-ppb levels or having poor ionisation efficiency. Furthermore, it was observed that retention time

  8. 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.

    PubMed

    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.

  9. 21 CFR 500.86 - Marker residue and target tissue.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Marker residue and target tissue. 500.86 Section...-Producing Animals § 500.86 Marker residue and target tissue. (a) For each edible tissue, the sponsor shall...) From these data, FDA will select a target tissue and a marker residue and designate the...

  10. 77 FR 24671 - Compliance Guide for Residue Prevention and Agency Testing Policy for Residues

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... increased testing animals from producers who are under an injunction obtained by the Food and Drug... addition, FSIS intends to increase its testing for residues in animals from producers who are under an... Food Safety and Inspection Service Compliance Guide for Residue Prevention and Agency Testing...

  11. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Methyl alcohol residues. 173.250 Section 173.250... CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the following foods under the conditions specified: (a) In...

  12. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Methyl alcohol residues. 173.250 Section 173.250... CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the following foods under the conditions specified: (a) In...

  13. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Methyl alcohol residues. 173.250 Section 173.250... CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the following foods under the conditions specified: (a) In...

  14. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Methyl alcohol residues. 173.250 Section 173.250... CONSUMPTION Solvents, Lubricants, Release Agents and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the following foods under the conditions specified: (a) In...

  15. 21 CFR 173.250 - Methyl alcohol residues.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Methyl alcohol residues. 173.250 Section 173.250... and Related Substances § 173.250 Methyl alcohol residues. Methyl alcohol may be present in the... specifies the presence of methyl alcohol and provides for the use of the hops extract only as prescribed...

  16. Pesticide residues in eagles

    USGS Publications Warehouse

    Reichel, W.L.; Cromartie, E.; Lamont, T.G.; Mulhern, B.M.; Prouty, R.M.

    1969-01-01

    Bald and golden eagles found sick or dead in 18 States and Canada during 1964-1965 were analyzed for pesticide residues. Residues in bald eagles were considerably higher than in golden eagles. Residues of DDE, DDD, and dieldrin were detected in all samples of bald eagle carcasses; other compounds found, less frequently were heptachlor epoxide, endrin, and DCBP, a metabolite of DDT. DDE was detected in all samples of golden eagle carcasses; DDD, DDT, dieldrin, and heptachlor epoxide were detected less frequently.

  17. Club Drugs

    MedlinePlus

    ... Rohypnol, ketamine, as well as MDMA (ecstasy) and methamphetamine ( Drug Facts: Club Drugs , National Institute on Drug ... Club Drugs , National Institute on Drug Abuse, 2010). Methamphetamine is a powerfully addictive stimulant associated with serious ...

  18. Drug discovery targeting human 5-HT2C receptors: Residues S3.36 and Y7.43 impact ligand—binding pocket structure via hydrogen bond formation

    PubMed Central

    Canal, Clinton E.; Cordova-Sintjago, Tania C.; Villa, Nancy Y.; Fang, Li-Juan; Booth, Raymond G.

    2011-01-01

    Specific activation of serotonin (5-HT) 5-HT2C G protein-coupled receptors may be therapeutic for obesity and neuropsychiatric disorders. Mutagenesis coupled with computational and molecular modeling experiments based on the human β2 adrenergic receptor structure were employed to delineate the interactions of different ligands at human 5-HT2C residues D3.32, S3.36 and Y7.43. No binding of the tertiary amine radioligand ([3H]-mesulergine) could be detected when the 5-HT2C D3.32 residue was mutated to alanine (D3.32A). The S3.36A point-mutation greatly reduced affinity of primary amine ligands, modestly reduced affinity of a secondary amine, and except for the 5-HT2C-specific agonist N(CH3)2-PAT, affinity of tertiary amines was unaffected. Molecular modeling results indicated that the primary amines form hydrogen bonds with the S3.36 residue, whereas, with the exception of N(CH3)2-PAT, tertiary amines do not interact considerably with this residue. The Y7.43A point-mutation greatly reduced affinity of 5-HT, yet reduced to a lesser extent the affinity of tryptamine that lacks the 5-hydroxy moiety present in 5-HT; modeling results indicated that the 5-HT 5-hydroxy moiety hydrogen bonds with Y7.43 at the 5-HT2C receptor. Additional modeling results showed that 5-HT induced a hydrogen bond between Y7.43 and D3.32. Finally, modeling results revealed two low-energy binding modes for 5-HT in the 5-HT2C binding pocket, supporting the concept that multiple agonist binding modes may stabilize different receptor active conformations to influence signaling. Ligand potencies for modulating WT and point-mutated 5-HT2C receptor-mediated phospholipase C activity were in accordance with the affinity data. Ligand efficacies, however, were altered considerably by the S3.36A mutation only. PMID:22020288

  19. Drug allergies

    MedlinePlus

    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 ...

  20. Drug Safety

    MedlinePlus

    ... 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 ...

  1. Residue chemistry guidelines.

    PubMed

    Olinger, C L; Schmitt, R D; Zager, E

    1993-01-01

    Residue chemistry guidelines are designed to determine what the potential residues in food are and how much may be present as a result of pesticide application, so that a tolerance level may be established. Some requirements are established to assist in the enforcement of tolerances by the USDA, FDA, and the states. I realize I have given you a quick overview of the residue chemistry requirements. There are many documents which are available if you should require more information, such as the Subdivision O Residue Chemistry Guidelines, Standard Evaluation Procedures (which are used by reviewers when evaluating the studies), the Data Reporting Guidelines (which provide guidance on preparing final reports), and the Technical Guidance from Phase III of Reregistration. We have also released various papers on studies when additional guidance is required. Most of these documents are available from NTIS. I hope you will consider this information when auditing residue chemistry studies. As I see the efforts that you, the QA professionals, have made to educate yourselves on residue chemistry studies through programs such as this meeting, I have a little more confidence in answering the question "Do you trust them?" with a "Yes." Thank you.

  2. 77 FR 14813 - Public Workshop on Minimal Residual Disease; Public Workshop

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

    ... HUMAN SERVICES Food and Drug Administration Public Workshop on Minimal Residual Disease; Public Workshop... residual disease (MRD) as a biomarker for evaluating new drugs for the treatment of acute lymphoblastic...., a measurable characteristic that is predictive of disease outcome) that can be used to...

  3. Determination of tricaine residues in fish by liquid chromatography.

    PubMed

    Nochetto, Cristina B; Reimschuessel, Renate; Gieseker, Charles; Cheely, Christie-Sue; Carson, Mary C

    2009-01-01

    Tricaine methanesulfonate (MS-222) is approved by the U.S. Food and Drug Administration, Center for Veterinary Medicine (CVM), as an anesthetic drug for select aquaculture species. It was approved for use as a handling aid with a 3 week withdrawal time. The drug is rapidly metabolized and excreted; therefore, CVM approved its use without requiring a regulatory method for drug residues in tissues. However, there are concerns that the drug may be used to sedate fish during transport to slaughter. A regulatory method will enable monitoring for unsafe residues of this drug resulting from extralabel use. We present a quantitative method, using LC at a target level of 0.1 mg/kg (ppm), for three different farmed species: salmon (Salmo salar); tilapia (Oreochromis spp.); and catfish (Ictalurus punctatus). The assay begins with an acetonitrile extraction, followed by filtration and mixed-mode cation-exchange solid-phase extraction cleanup. The extracts are analyzed by reversed-phase LC with UV detection at 320 nm. The method was validated by using fish fillets with incurred residues, control fish fillets, and fish fillets fortified at half the target level, the target level, and twice the target level (0.05, 0.1, and 0.2 ppm, respectively). For all species, accuracy is > or =80% and the RSD is < or =10%. The method complies with CVM performance criteria for the determination of veterinary drug residues. PMID:19714996

  4. Residue depletion of tilmicosin in chicken tissues.

    PubMed

    Zhang, Yue; Jiang, Haiyang; Jin, Xingjun; Shen, Zhangqi; Shen, Jianzhong; Fu, Caixia; Guo, Junlin

    2004-05-01

    A high-performance liquid chromatography (HPLC) method with detection at 290 nm was modified and validated for the determination of tilmicosin residues in broiler chicken tissues. The limits of detection (LOD) of the method were 0.01 microg/g for muscle and 0.025 microg/g for liver and kidney. Average recoveries ranged from 80.4 to 88.3%. Relative standard deviation values ranged from 5.2 to 12.1%. Residue depletion of tilmicosin in broiler chickens was examined after dosing over a 5-day period by incorporation of the drug into drinking water at 37.5 and 75.0 mg/L. Tilmicosin concentrations in liver and kidney were highest on day 3 of medication and on day 5 in muscle, in both low- and high-dose groups. The residue levels in both groups were significantly higher in liver than in kidney or muscle. A minimum withdrawal time of 9 days was indicated for residue levels in muscle, liver, and kidney tissues below the maximum residue level (MRL).

  5. Drug Resistance

    MedlinePlus

    HIV Treatment Drug Resistance (Last updated 3/1/2016; last reviewed 3/1/2016) Key Points As HIV multiplies in the ... the risk of drug resistance. What is HIV drug resistance? Once a person becomes infected with HIV, ...

  6. Development and model testing of anti-mortem screening methodology to predict prescribed drug withholds in heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A simple, cow-side test for the presence of drug residues in live animal fluids would provide useful information for tissue drug residue avoidance programs. This work describes adaptation and evaluation of rapid screening tests to detect drug residues in serum and urine. Medicated herd animals had...

  7. Development and model testing of anti-mortem screening methodology to predict prescribed drug withholds in heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A simple, cow-side test for the presence of drug residues in live animal fluids would provide useful information for tissue drug residue avoidance programs. Live animal tests have the potential to allow verification that an individual animal is free of drug residues before sale for h...

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

    PubMed

    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. PMID:25864054

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

    PubMed

    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.

  10. Residual stresses in material processing

    SciTech Connect

    Kozaczek, K.J.; Watkins, T.R.; Hubbard, C.R.; Wang, Xun-Li; Spooner, S.

    1994-09-01

    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 adresses 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.

  11. 40 CFR 1065.705 - Residual and intermediate residual fuel.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... specifications for fuels meeting the definition of residual fuel in 40 CFR 80.2, including fuels marketed as... for Residual Fuel Characteristic Unit Category ISO-F- RMA 30 RMB 30 RMD 80 RME 180 RMF 180 RMG 380...

  12. 40 CFR 1065.705 - Residual and intermediate residual fuel.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... specifications for fuels meeting the definition of residual fuel in 40 CFR 80.2, including fuels marketed as... for Residual Fuel Characteristic Unit Category ISO-F- RMA 30 RMB 30 RMD 80 RME 180 RMF 180 RMG 380...

  13. SRC Residual fuel oils

    DOEpatents

    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.

  14. Water treatment residuals

    SciTech Connect

    Billings, C.H.

    1994-01-01

    Solutions to an environmental problem often create other environmental problems. That surely is the case in the water supply field. By providing new or expanded water treatment systems to comply with the maximum contaminant levels and treatment mandates of the Safe Drinking Water Act, water purveyors are generating large volumes of residuals that must be managed, ultimately disposed of, or recycled. Numerous federal, state, and local laws govern the management, transport, disposal, and recycling of wastes produced by water treatment systems. Because these laws can result in exorbitant waste disposal costs, restricting some projects entirely, water suppliers need to consider residual disposal early in the siting, selection, and design of treatment projects. To inform water suppliers about residual laws, AWWA commissioned a study published as a Water Industry Technical Action Fund report. In addition to identifying and describing applicable laws at the federal level and in six of the states, the study revealed a series of findings as to the consequences of those laws to water suppliers. This article is a brief overview of the findings of the report.

  15. Low-residue euthanasia of stranded mysticetes.

    PubMed

    Harms, Craig A; McLellan, William A; Moore, Michael J; Barco, Susan G; Clarke, Elsburgh O; Thayer, Victoria G; Rowles, Teresa K

    2014-01-01

    Euthanasia of stranded large whales poses logistic, safety, pharmaceutical, delivery, public relations, and disposal challenges. Reasonable arguments may be made for allowing a stranded whale to expire naturally. However, slow cardiovascular collapse from gravitational effects outside of neutral buoyancy, often combined with severely debilitating conditions, motivate humane efforts to end the animal's suffering. The size of the animal and prevailing environmental conditions often pose safety concerns for stranding personnel, which take priority over other considerations. When considering chemical euthanasia, the size of the animal also necessitates large quantities of euthanasia agents. Drug residues are a concern for relay toxicity to scavengers, particularly for pentobarbital-containing euthanasia solutions. Pentobarbital is also an environmental concern because of its stability and long persistence in aquatic environments. We describe a euthanasia technique for stranded mysticetes using readily available, relatively inexpensive, preanesthetic and anesthetic drugs (midazolam, acepromazine, xylazine) followed by saturated KCl delivered via custom-made needles and a low-cost, basic, pressurized canister. This method provides effective euthanasia while moderating personnel exposure to hazardous situations and minimizing drug residues of concern for relay toxicity.

  16. Drug Abuse

    MedlinePlus

    ... as drugged driving, violence, stress, and child abuse. Drug abuse can lead to homelessness, crime, and missed work or problems with keeping a job. It harms unborn babies and destroys families. There are different types of treatment for drug abuse. But the best is to prevent drug ...

  17. Controlled drugs.

    PubMed

    2016-05-18

    Essential facts Controlled drugs are defined and governed by the Misuse of Drugs Act 1971 and associated regulations. Examples of controlled drugs include morphine, pethidine and methadone. Since 2012, appropriately qualified nurses and midwives can prescribe controlled drugs for medical conditions within their competence. There are some exceptions when treating addiction. PMID:27191427

  18. Residual Viremia in Treated HIV+ Individuals

    DOE PAGESBeta

    Conway, Jessica M.; Perelson, Alan S.

    2016-01-06

    Antiretroviral therapy (ART) effectively controls HIV infection, suppressing HIV viral loads. However, some residual virus remains, below the level of detection, in HIV-infected patients on ART. Furthermore, the source of this viremia is an area of debate: does it derive primarily from activation of infected cells in the latent reservoir, or from ongoing viral replication? Our observations seem to be contradictory: there is evidence of short term evolution, implying that there must be ongoing viral replication, and viral strains should thus evolve. The phylogenetic analyses, and rare emergent drug resistance, suggest no long-term viral evolution, implying that virus derived frommore » activated latent cells must dominate. We use simple deterministic and stochastic models to gain insight into residual viremia dynamics in HIV-infected patients. Our modeling relies on two underlying assumptions for patients on suppressive ART: that latent cell activation drives viral dynamics and that the reproductive ratio of treated infection is less than 1. Nonetheless, the contribution of viral replication to residual viremia in patients on ART may be non-negligible. However, even if the portion of viremia attributable to viral replication is significant, our model predicts (1) that latent reservoir re-seeding remains negligible, and (2) some short-term viral evolution is permitted, but long-term evolution can still be limited: stochastic analysis of our model shows that de novo emergence of drug resistance is rare. Thus, our simple models reconcile the seemingly contradictory observations on residual viremia and, with relatively few parameters, recapitulates HIV viral dynamics observed in patients on suppressive therapy.« less

  19. The residual caries dilemma.

    PubMed

    Weerheijm, K L; Groen, H J

    1999-12-01

    Restorative dentistry is based on the assumption that bacterial infection of demineralized dentine should prompt operative intervention. One of the concepts of practical dentistry is to create a favourable environment for caries arrest with minimal operative intervention. The progress of remaining primary caries is key to any discussion of this concept. This discussion is important for the atraumatic restorative treatment (ART) approach, since the removal of all carious dentine is sometimes difficult using hand instruments only. In this paper the results of possible measures to guard against the effects of residual carious and its consequences are reviewed, in order to obtain an impression of the justification for (in)complete excavation of occlusal dentinal caries. Three types of measure are considered: isolating the caries process from the oral environment, excavating the carious dentine, and using a cariostatic filling material. Each of these measures contributes to the arrest of the caries process. However, none of these measures can arrest this process by itself. A combination of all three seems necessary. It is concluded that although residual caries does not seem to be the criterion for rerestoration, one has to strive for as complete caries removal as possible. If this cannot be fulfilled the sealing capacities of the filling material seem to be more important than its cariostatic properties. PMID:10600078

  20. Residues of clenbuterol in cattle receiving therapeutic doses: implications for differentiating between legal and illegal use.

    PubMed

    Elliot, C T; McCaughey, W J; Crooks, S R; McEvoy, J D; Kennedy, D G

    1995-09-01

    Clenbuterol (CBL) can be used legally in the treatment of respiratory diseases and illegally as a growth promoter in animals. Liver and eye have previously been shown to be effective matrices for the detection of residual concentrations of the drug. The pharmacokinetics of CBL in therapeutically treated cattle were investigated. During treatment, many body fluids and tissues contained residues of the drug. After a 14 day withdrawal only eyes (mean 27.1 micrograms/kg), and to a much lesser extent lung and kidney (mean 0.3 micrograms/kg), contained detectable residues. By day 28 of withdrawal only residues in eyes were present (mean, 6 micrograms/kg). These persisted to the end of the trial (42 days withdrawal). It is concluded that it is not possible to differentiate between the legal and illegal use of CBL solely on drug residue analysis. Other information must be made available to regulatory bodies to enforce control programmes.

  1. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-01-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing. PMID:27441421

  2. Drug Debacle.

    PubMed

    Sorrel, Amy Lynn

    2016-07-01

    Medicaid's Vendor Drug Program is under examination by the Texas Legislature. TMA's Physicians Medicaid Congress is seizing the opportunity to call for an administrative overhaul of a drug benefit physicians describe as unnecessarily complicated and confusing.

  3. Drugged Driving

    MedlinePlus

    ... Infographics » Drugged Driving Drugged Driving Email Facebook Twitter Text Description of Infographic Top Right Figure : In 2009, ... crash than those who don't smoke. Bottom Text: Develop Social Strategies Offer to be a designated ...

  4. Drug Control

    ERIC Educational Resources Information Center

    Leviton, Harvey S.

    1975-01-01

    This article attempts to assemble pertinent information about the drug problem, particularily marihuana. It also focuses on the need for an educational program for drug control with the public schools as the main arena. (Author/HMV)

  5. Generic Drugs

    MedlinePlus

    ... drugs. There are a few other differences— like color, shape, size, or taste—but they do not ... different . Brand-name drugs are often advertised by color and shape. Remember the ads for the “purple ...

  6. Residual gas analyzer calibration

    NASA Technical Reports Server (NTRS)

    Lilienkamp, R. H.

    1972-01-01

    A technique which employs known gas mixtures to calibrate the residual gas analyzer (RGA) is described. The mass spectra from the RGA are recorded for each gas mixture. This mass spectra data and the mixture composition data each form a matrix. From the two matrices the calibration matrix may be computed. The matrix mathematics requires the number of calibration gas mixtures be equal to or greater than the number of gases included in the calibration. This technique was evaluated using a mathematical model of an RGA to generate the mass spectra. This model included shot noise errors in the mass spectra. Errors in the gas concentrations were also included in the valuation. The effects of these errors was studied by varying their magnitudes and comparing the resulting calibrations. Several methods of evaluating an actual calibration are presented. The effects of the number of gases in then, the composition of the calibration mixture, and the number of mixtures used are discussed.

  7. SWIR hyperspectral imaging detector for surface residues

    NASA Astrophysics Data System (ADS)

    Nelson, Matthew P.; Mangold, Paul; Gomer, Nathaniel; Klueva, Oksana; Treado, Patrick

    2013-05-01

    ChemImage has developed a SWIR Hyperspectral Imaging (HSI) sensor which uses hyperspectral imaging for wide area surveillance and standoff detection of surface residues. Existing detection technologies often require close proximity for sensing or detecting, endangering operators and costly equipment. Furthermore, most of the existing sensors do not support autonomous, real-time, mobile platform based detection of threats. The SWIR HSI sensor provides real-time standoff detection of surface residues. The SWIR HSI sensor provides wide area surveillance and HSI capability enabled by liquid crystal tunable filter technology. Easy-to-use detection software with a simple, intuitive user interface produces automated alarms and real-time display of threat and type. The system has potential to be used for the detection of variety of threats including chemicals and illicit drug substances and allows for easy updates in the field for detection of new hazardous materials. SWIR HSI technology could be used by law enforcement for standoff screening of suspicious locations and vehicles in pursuit of illegal labs or combat engineers to support route-clearance applications- ultimately to save the lives of soldiers and civilians. In this paper, results from a SWIR HSI sensor, which include detection of various materials in bulk form, as well as residue amounts on vehicles, people and other surfaces, will be discussed.

  8. Drug Interactions

    PubMed Central

    Tong Logan, Angela; Silverman, Andrew

    2012-01-01

    One of the most clinically significant complications related to the use of pharmacotherapy is the potential for drug-drug or drug-disease interactions. The gastrointestinal system plays a large role in the pharmacokinetic profile of most medications, and many medications utilized in gastroenterology have clinically significant drug interactions. This review will discuss the impact of alterations of intestinal pH, interactions mediated by phase I hepatic metabolism enzymes and P-glycoprotein, the impact of liver disease on drug metabolism, and interactions seen with commonly utilized gastrointestinal medications. PMID:22933873

  9. Experimental determination of residual stress

    NASA Technical Reports Server (NTRS)

    Ferguson, Milton W.

    1991-01-01

    Residual stresses in finished parts have often been regarded as factors contributing to premature part failure and geometric distortions. Currently, residual stresses in welded structures and railroad components are being investigated. High residual stresses formed in welded structures due primarily to the differential contractions of the weld material as it cools and solidifies can have a profound effect on the surface performance of the structure. In railroad wheels, repeated use of the brakes causes high residual stresses in the rims which may lead to wheel failure and possible derailment. The goals of the study were: (1) to develop strategies for using x-ray diffraction to measure residual stress; (2) to subject samples of Inconel 718 to various mechanical and heat treatments and to measure the resulting stress using x-ray diffraction; and (3) to measure residual stresses in ferromagnetic alloys using magnetoacoustics.

  10. Materials recovery from shredder residues

    SciTech Connect

    Daniels, E. J.; Jody, B. J.; Pomykala, J., Jr.

    2000-07-24

    Each year, about five (5) million ton of shredder residues are landfilled in the US. Similar quantities are landfilled in Europe and the Pacific Rim. Landfilling of these residues results in a cost to the existing recycling industry and also represents a loss of material resources that are otherwise recyclable. In this paper, the authors outline the resources recoverable from typical shredder residues and describe technology that they have developed to recover these resources.

  11. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  12. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  13. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  14. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  15. 9 CFR 318.20 - Use of animal drugs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Use of animal drugs. 318.20 Section 318.20 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... General § 318.20 Use of animal drugs. Animal drug residues are permitted in meat and meat food products...

  16. COPD - control drugs

    MedlinePlus

    Chronic obstructive pulmonary disease - control drugs; Bronchodilators - COPD - control drugs; Beta agonist inhaler - COPD - control drugs; Anticholinergic inhaler - COPD - control drugs; Long-acting inhaler - COPD - control drugs; ...

  17. Analysis of fenbendazole residues in bovine milk by ELISA.

    PubMed

    Brandon, David L; Bates, Anne H; Binder, Ronald G; Montague, William C; Whitehand, Linda C; Barker, Steven A

    2002-10-01

    Fenbendazole residues in bovine milk were analyzed by ELISAs using two monoclonal antibodies. One monoclonal antibody (MAb 587) bound the major benzimidazole anthelmintic drugs, including fenbendazole, oxfendazole, and fenbendazole sulfone. The other (MAb 591) was more specific for fenbendazole, with 13% cross-reactivity with the sulfone and no significant binding to the sulfoxide metabolite. The limit of detection of the ELISA method in the milk matrix was 7 ppb for MAb 587 and 3 ppb for MAb 591. Fenbendazole was administered in feed, drench, and paste form to three groups of dairy cattle. Milk was collected immediately before dosing and then every 12 h for 5 days. The ELISA indicated that residue levels varied widely among individual cows in each group. Fenbendazole levels peaked at approximately 12-24 h and declined rapidly thereafter. Metabolites were detected at much higher levels than the parent compound, peaked at approximately 24-36 h, and declined gradually. Residue levels were undetectable by 72 h. The ELISA data correlated well with the total residues determined by chromatographic analysis, but the use of the two separate ELISAs did not afford an advantage over ELISA with the single, broadly reactive MAb 587. The ELISA method could be used to flag high-residue samples in on-site monitoring of fenbendazole in milk and is a potential tool for studying drug pharmacokinetics.

  18. On tide-induced lagrangian residual current and residual transport: 1. Lagrangian residual current

    USGS Publications Warehouse

    Feng, Shizuo; Cheng, Ralph T.; Pangen, Xi

    1986-01-01

    Residual currents in tidal estuaries and coastal embayments have been recognized as fundamental factors which affect the long-term transport processes. It has been pointed out by previous studies that it is more relevant to use a Lagrangian mean velocity than an Eulerian mean velocity to determine the movements of water masses. Under weakly nonlinear approximation, the parameter k, which is the ratio of the net displacement of a labeled water mass in one tidal cycle to the tidal excursion, is assumed to be small. Solutions for tides, tidal current, and residual current have been considered for two-dimensional, barotropic estuaries and coastal seas. Particular attention has been paid to the distinction between the Lagrangian and Eulerian residual currents. When k is small, the first-order Lagrangian residual is shown to be the sum of the Eulerian residual current and the Stokes drift. The Lagrangian residual drift velocity or the second-order Lagrangian residual current has been shown to be dependent on the phase of tidal current. The Lagrangian drift velocity is induced by nonlinear interactions between tides, tidal currents, and the first-order residual currents, and it takes the form of an ellipse on a hodograph plane. Several examples are given to further demonstrate the unique properties of the Lagrangian residual current.

  19. Drug Research

    NASA Technical Reports Server (NTRS)

    1989-01-01

    NBOD2, a program developed at Goddard Space Flight Center to solve equations of motion coupled N-body systems is used by E.I. DuPont de Nemours & Co. to model potential drugs as a series of elements. The program analyses the vibrational and static motions of independent components in drugs. Information generated from this process is used to design specific drugs to interact with enzymes in designated ways.

  20. Prevalence of antimicrobial residues in raw table eggs from farms and retail outlets in Enugu State, Nigeria.

    PubMed

    Ezenduka, Ekene V; Oboegbulem, Steve I; Nwanta, John A; Onunkwo, Joseph I

    2011-03-01

    The use of antimicrobial agents in poultry production results in their accumulation in the body tissues and products such as milk and egg. The subsequent accumulation of these drugs and their metabolites in body cells is known as drug residue. This study was designed to determine the prevalence of antimicrobial residues in eggs from poultry farms and retail outlets in Enugu State, Nigeria. Eggs from 25 selected commercial farms and ten retail outlets were screened for the prevalence of antimicrobial residue. Also, structured questionnaires were administered to 25 commercial farms in the state to determine the management practices and the most widely used antimicrobial drugs in farms and possible association between the management practices and the occurrence of antimicrobial residues in eggs from these farms. All the 25 farms surveyed use oxytetracycline. Eggs from nine of the surveyed farms tested positive for antimicrobial residue and three of the ten surveyed farms also tested positive for antimicrobial residue. No association was observed (p 0.05; Fisher's exact test) between the occurrence of antibiotic residues in eggs and farm size, feed source and housing systems. This study was able to demonstrate the presence of antimicrobial residues in eggs destined for human consumption. Drugs like nitrofurans which has been banned for use in food animals are still very much in use in Enugu State, Nigeria. Antibiotics given as feed additives may give rise to drug residues in food animals. PMID:21104128

  1. Fungicide residues in strawberry processing.

    PubMed

    Will, F; Krüger, E

    1999-03-01

    The fate of three fungicides (dichlofluanid, procymidone, and iprodione) applied under field conditions was studied during strawberry processing to juice, wine, and jam. An untreated control was compared to raw material treated with fungicides according to recommended doses and to a sample with 6-fold higher application rates. The highest residue values were found in the pomace after pressing. Residue values in readily produced juices and fruit wines were very low and did not exceed legally required maximum residue levels. Generally, processing steps such as pressing and clarification diminished fungicide residues from 50 to 100%. If the whole fruit is processed, as in fruit preparations or jam, the residue levels remain higher due to missing processing steps. PMID:10552381

  2. [Drug dependence and psychotropic drugs].

    PubMed

    Giraud, M J; Lemonnier, E; Bigot, T

    1994-11-01

    Although the utility of psychotropic drugs has been well demonstrated, caution must still be exercised in their use. Among their potential risks, drug dependency must be kept in mind. This risk is well accepted with regard to benzodiazepines, and it appeared useful to study the potential risk for antidepressants, neuroleptics and thymoregulatory agents. Whatever the drug, the predominant factor appears to be psychological dependency. Prevention of drug dependency is most often achieved by informing the patient, limiting the length of use of the drug, making regular reevaluation of symptoms and of drug indication, and frequently be establishing a "treatment contract". The importance of the patient-physician relationship in the prescription of such treatment must be underlined. PMID:7984941

  3. Drug Education.

    ERIC Educational Resources Information Center

    Sardana, Raj K.

    This autoinstructional lesson deals with the study of such drugs as marijuana and LSD, with emphasis on drug abuse. It is suggested that it can be used in science classes at the middle level of school. No prerequisites are suggested. The teacher's guide lists the behavioral objectives, the equipment needed to complete the experience and suggests…

  4. Antineoplastic Drugs

    NASA Astrophysics Data System (ADS)

    Sadée, Wolfgang; El Sayed, Yousry Mahmoud

    The limited scope of therapeutic drug-level monitoring in cancer chemotherapy results from the often complex biochemical mechanisms that contribute to antineoplastic activity and obscure the relationships among drug serum levels and therapeutic benefits. Moreover, new agents for cancer chemotherapy are being introduced at a more rapid rate than for the treatment of other diseases, although the successful application of therapeutic drug-level monitoring may require several years of intensive study of the significance of serum drug levels. However, drug level monitoring can be of considerable value during phase I clinical trials of new antineoplastic agents in order to assess drug metabolism, bioavailability, and intersubject variability; these are important parameters in the interpretation of clinical studies, but have no immediate benefit to the patient. High performance liquid chromatography (HPLC) probably represents the most versatile and easily adaptable analytical technique for drug metabolite screening (1). HPLC may therefore now be the method of choice during phase I clinical trials of antineoplastic drugs. For example, within a single week we developed an HPLC assay—using a C18 reverse-phase column, UV detection, and direct serum injection after protein precipitation—for the new radiosensitizer, misonidazole (2).

  5. Results of anti-mortem screening methodology to predict prescribed drug withholding periods for flunixin and ceftiofur in heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Introduction: A simple, cow-side test for the presence of drug residues in live animals would be useful for drug residue avoidance programs. Simple inhibition tests used at slaughter do not detect some drug tolerance concentrations such as those for flunixin and ceftiofur-metabolites. This experim...

  6. Rapid depletion of marbofloxacin residues in rabbit after therapeutic treatment.

    PubMed

    Ligabue, Matteo; Lucchetti, Dario; Catone, Tiziana; Fabrizi, Laura; Marvasi, Luigi; Zaghini, Anna; Coni, Ettore

    2005-11-01

    Although rabbit meat production represents a very small percentage of the world meat market, this percentage has been growing continuously during the last 30 years. Rabbit is considered a minor food species, and therefore no drugs are specifically registered for this animal. This situation encourages rabbit farmers to make off-label use of antibacterial drugs authorized for food-producing animal species other than rabbits. In the present study, the distribution and elimination of the fluoroquinolone antibacterial agent marbofloxacin in rabbit muscle, liver, and kidney was investigated. Marbofloxacin was chosen as a representative of a new generation of antibacterial drugs active against most gram-positive and gram-negative bacteria and mycoplasms; it is well tolerated and has short elimination times in bovine and swine species. Rabbits were treated with marbofloxacin at 2 mg kg of body weight(-1) for 5 days. Residual concentrations in liver, kidney, and muscle tissues were determined posttreatment with high-performance liquid chromatography and fluorescence detection. Marbofloxacin was rapidly distributed and eliminated from rabbit tissues. Concentrations were higher in the liver and kidney than in muscle. However, 48 h after the end of treatment, marbofloxacin concentrations dropped below the maximum residue level fixed for this antibacterial drug in cattle and pigs. Considering the efficacy of marbofloxacin for the treatment of the most common rabbit diseases, its tolerability, and its short elimination time as verified in the present study, use of this antibacterial drug could be extended to therapeutic treatment of rabbits.

  7. Multiple myeloma, immunotherapy and minimal residual disease.

    PubMed

    Kusenda, J; Kovarikova, A

    2016-01-01

    Multiple myeloma (MM) is an incurable heterogeneous hematological malignancy in which relapse is characterized by re-growth of residual tumor and immune suppression with a complex biology that affects many aspects of the disease and its response to treatment. The bone marrow microenvironment, including immune cells, plays a central role in MM pathogenesis, survival, and drug resistance. The advances in basic and translational research, introduction of novel agents, particularly combination therapies, improved indicators of quality of life and survival. Minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) has revolutionized monitoring of treatment response in MM. The importance of MFC methodology will be further strengthened by the ongoing international standardization efforts. Results of MRD testing provide unique and clinically important information and demonstrated the prognostic significance of MRD in patients, leading to regulate treatment intensity in many contemporary protocols. In this review, we will summarize the principal approaches in MM immunotherapy, focusing how new agents have potential in the treatment of MM and application of MRD detection by MFC as a surrogate endpoint would allow quicker evaluation of treatment outcomes and rapid identification of effective new therapies.

  8. Americium recovery from reduction residues

    DOEpatents

    Conner, W.V.; Proctor, S.G.

    1973-12-25

    A process for separation and recovery of americium values from container or bomb'' reduction residues comprising dissolving the residues in a suitable acid, adjusting the hydrogen ion concentration to a desired level by adding a base, precipitating the americium as americium oxalate by adding oxalic acid, digesting the solution, separating the precipitate, and thereafter calcining the americium oxalate precipitate to form americium oxide. (Official Gazette)

  9. Street Drugs and Pregnancy

    MedlinePlus

    ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ... drugs that are abused How can street drugs harm your pregnancy? Using street drugs can cause problems ...

  10. Prescription Drugs

    MedlinePlus

    ... body, especially in brain areas involved in the perception of pain and pleasure. Prescription stimulants , such as ... of drug that causes changes in your mood, perceptions, and behavior can affect judgment and willingness to ...

  11. Antiretroviral drugs.

    PubMed

    De Clercq, Erik

    2010-10-01

    In October 2010, it will be exactly 25 years ago that the first antiretroviral drug, AZT (zidovudine, 3'-azido-2',3'-dideoxythymidine), was described. It was the first of 25 antiretroviral drugs that in the past 25 years have been formally licensed for clinical use. These antiretroviral drugs fall into seven categories [nucleoside reverse transcriptase inhibitors (NRTIs), nucleotide reverse transcriptase inhibitors (NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), co-receptor inhibitors (CRIs) and integrase inhibitors (INIs). The INIs (i.e. raltegravir) represent the most recent advance in the search for effective and selective anti-HIV agents. Combination of several anti-HIV drugs [often referred to as highly active antiretroviral therapy (HAART)] has drastically altered AIDS from an almost uniformly fatal disease to a chronic manageable one.

  12. Drug Reactions

    MedlinePlus

    ... or diabetes. But medicines can also cause unwanted reactions. One problem is interactions, which may occur between ... more serious. Drug allergies are another type of reaction. They can be mild or life-threatening. Skin ...

  13. Club Drugs

    MedlinePlus

    Skip to main content En español Researchers Medical & Health Professionals Patients & ... Cold Medicines Steroids (Anabolic) Synthetic Cannabinoids (K2/Spice) Synthetic Cathinones (Bath Salts) Tobacco/Nicotine Other Drugs ...

  14. Drugged Driving

    MedlinePlus

    ... Charts Emerging Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine ... distance, and decrease coordination. Drivers who have used cocaine or methamphetamine can be aggressive and reckless when ...

  15. Drug Interactions

    MedlinePlus

    ... not be taken at the same time as antacids. WHAT CAUSES THE MOST INTERACTIONS WITH HIV MEDICATIONS? ... azole” Some antibiotics (names end in “mycin”) The antacid cimetidine (Tagamet) Some drugs that prevent convulsions, including ...

  16. Club Drugs

    MedlinePlus

    ... also known as Ecstasy XTC, X, E, Adam, Molly, Hug Beans, and Love Drug Gamma-hydroxybutyrate (GHB), also known as G, Liquid Ecstasy, and Soap Ketamine, also known as Special K, K, Vitamin K, and Jet Rohypnol, also known ...

  17. Detecting ketamine in beverage residues: Application in date rape detection.

    PubMed

    Albright, Jessica A; Stevens, Sarah A; Beussman, Douglas J

    2012-05-01

    Ketamine can be used to facilitate date-rape when unknowingly spiked into a victim's beverage. If a biological sample is not available from the victim, the beverage container might be the only remaining source of forensic evidence. We present a rapid, simple analysis method for the detection of ketamine in wet or dry beverage residues based on liquid chromatography-mass spectrometry (LC-MS). Wet residues consist of the final few drops (<1 ml) in a container while dry residues are the remains once all liquid has evaporated. By using LC-MS, which readily handles aqueous samples, often no derivatization or sample extraction is needed, thus reducing analysis time and lab technician involvement. Tandem mass spectrometry (MS/MS) provides an enhancement in both selectivity and sensitivity. We have studied a range of beverages and determined limits of detection between 1.2 × 10-3 and 1.3 × 10-4 mg/ml, compared to 0.21-0.85 mg/ml used in most date-rape scenarios. This paper represents the first published report of using LC-MS/MS for the analysis of beverage residues for the presence of a date-rape drug. This method could replace the current gas chromatography-mass spectrometry (GC-MS) methods and provide a faster, more selective method for the analysis of date-rape drugs, requiring virtually no sample preparation. PMID:22114065

  18. Drug allergy

    PubMed Central

    Warrington, Richard

    2012-01-01

    Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

  19. A review of coccidiostats and the analysis of their residues in meat and other food.

    PubMed

    Clarke, Lesa; Fodey, Terence L; Crooks, Steven R H; Moloney, Mary; O'Mahony, John; Delahaut, Philippe; O'Kennedy, Richard; Danaher, Martin

    2014-07-01

    Coccidiostats are used in the control of protozoan infections in different food producing animals. They are most widely used as feed additives in intensively reared species such as pigs and poultry to maintain animal health and in some cases enhance feed conversion. However, a number of these drugs are used in the control of infections in beef and lamb production. Coccidiostat residues have been frequently reported in meat and eggs in a number of countries since the late 1990s. This has prompted increased research and surveillance of coccidiostat residues in food. This paper reviews the various coccidiostat agents used in animal production, including their chemical properties, mode of action and activity. Legislation concerning coccidiostats, limits for residues in food, monitoring and occurrence of residues in food is discussed. Methods for residue determination in food, including screening and physicochemical methods are discussed in depth. The paper concludes with a synopsis of the current state of coccidiostat residue analysis and future perspectives.

  20. DISSOLUTION OF NEPTUNIUM OXIDE RESIDUES

    SciTech Connect

    Kyser, E

    2009-01-12

    This report describes the development of a dissolution flowsheet for neptunium (Np) oxide (NpO{sub 2}) residues (i.e., various NpO{sub 2} sources, HB-Line glovebox sweepings, and Savannah River National Laboratory (SRNL) thermogravimetric analysis samples). Samples of each type of materials proposed for processing were dissolved in a closed laboratory apparatus and the rate and total quantity of off-gas were measured. Samples of the off-gas were also analyzed. The quantity and type of solids remaining (when visible) were determined after post-dissolution filtration of the solution. Recommended conditions for dissolution of the NpO{sub 2} residues are: Solution Matrix and Loading: {approx}50 g Np/L (750 g Np in 15 L of dissolver solution), using 8 M nitric acid (HNO{sub 3}), 0.025 M potassium fluoride (KF) at greater than 100 C for at least 3 hours. Off-gas: Analysis of the off-gas indicated nitric oxide (NO), nitrogen dioxide (NO{sub 2}) and nitrous oxide (N{sub 2}O) as the only identified components. No hydrogen (H{sub 2}) was detected. The molar ratio of off-gas produced per mole of Np dissolved ranged from 0.25 to 0.4 moles of gas per mole of Np dissolved. A peak off-gas rate of {approx}0.1 scfm/kg bulk oxide was observed. Residual Solids: Pure NpO{sub 2} dissolved with little or no residue with the proposed flowsheet but the NpCo and both sweepings samples left visible solid residue after dissolution. For the NpCo and Part II Sweepings samples the residue amounted to {approx}1% of the initial material, but for the Part I Sweepings sample, the residue amounted to {approx}8 % of the initial material. These residues contained primarily aluminum (Al) and silicon (Si) compounds that did not completely dissolve under the flowsheet conditions. The residues from both sweepings samples contained minor amounts of plutonium (Pu) particles. Overall, the undissolved Np and Pu particles in the residues were a very small fraction of the total solids.

  1. [Oxytetracycline and oxolinic acid residues in kuruma prawn (Penaeus japonicus) and the effect of cooking procedures on the residues].

    PubMed

    Uno, Kazuaki

    2002-04-01

    Tissue distribution and residue depletion of oxytetracycline (OTC) and oxolinic acid (OA) were studied in the kuruma prawn (Penaeus japonicus). The prawn were kept in tanks with recirculated artificial seawater at a salinity of 22-23@1000. The water temperature was maintained at 25 degrees C. The average body weight was 22.9 +/- 4.9 g for OTC and 22.5 +/- 3.6 g for OA. The drug was mixed with the diet and orally administered through a catheter to the prawn. The doses of OTC and OA, respectively, were 50 mg/kg body weight. At each sample time, four prawns were sacrificed and tissues were sampled. OTC and OA levels were determined by high-performance liquid chromatography. At the highest levels, the concentrations of OTC were in the other: shell (13.57 micrograms/g) > hemolymph (12.20 micrograms/mL) > muscle (8.30 micrograms/g). For OA, the order was: shell (20.74 micrograms/g) > hemolymph (7.06 micrograms/mL) > muscle (2.05 micrograms/g). The elimination half-lives of hemolymph and muscle were 44.7 and 46.8 hours for OTC and 55.0 and 107.9 hours for OA, respectively. Residual OTC could not be detected in hemolymph and muscle at 20 days after dosing. Residual OA disappeared from hemolymph and muscle at 25 days after dosing. A 25-day period for OTC and 30-day period for OA could be regarded as the proper withdrawal time established for kuruma prawn by the Pharmaceutical Law in Japan. However, the elimination half-lives of shell for OTC and OA could not be calculated because both drug residues persisted in shell tissues, and the elimination phase was not completed during the experimental period. Residual OTC (14.10 +/- 2.26 micrograms/g, n = 6) and OA (0.32 +/- 0.06 microgram/g, n = 7) were detected in exuviae at 3 days and 4 days after dosing, respectively. Residual OTC was reduced to 50-70% in muscle by the usual methods of cooking (boiling, baking at 200 degrees C and frying at 180 degrees C), whereas reduction levels in shell were only 20-30%. Residual OA was

  2. Residual stresses in welded plates

    NASA Technical Reports Server (NTRS)

    Bernstein, Edward L.

    1994-01-01

    The purpose of this project was to develop a simple model which could be used to study residual stress. The mechanism that results in residual stresses in the welding process starts with the deposition of molten weld metal which heats the immediately adjacent material. After solidification of weld material, normal thermal shrinkage is resisted by the adjacent, cooler material. When the thermal strain exceeds the elastic strain corresponding to the yield point stress, the stress level is limited by this value, which decreases with increasing temperature. Cooling then causes elastic unloading which is restrained by the adjoining material. Permanent plastic strain occurs, and tension is caused in the region immediately adjacent to the weld material. Compression arises in the metal farther from the weld in order to maintain overall static equilibrium. Subsequent repair welds may add to the level of residual stresses. The level of residual stress is related to the onset of fracture during welding. Thus, it is of great importance to be able to predict the level of residual stresses remaining after a weld procedure, and to determine the factors, such as weld speed, temperature, direction, and number of passes, which may affect the magnitude of remaining residual stress. It was hoped to use traditional analytical modeling techniques so that it would be easier to comprehend the effect of these variables on the resulting stress. This approach was chosen in place of finite element methods so as to facilitate the understanding of the physical processes. The accuracy of the results was checked with some existing experimental studies giving residual stress levels found from x-ray diffraction measurements.

  3. Drug misuse.

    PubMed Central

    Waller, T.

    1992-01-01

    1. Assessment by history and examination should include: a history of all drugs taken during each day for the previous 7 days (including alcohol), length of drug use and route (including the sharing of needles or syringes), the possibility of pregnancy if female, previous psychiatric history and treatment of drug misuse, social factors (including employment, family, friends, involvement in prostitution, legal problems), medical problems, including evidence of hepatitis, injection abscesses and other infections, suicide attempts, and weight loss. 2. Notification to the Chief Medical Officer of the Drug Branch of the Home Office is a legal obligation. 3. Investigations include: liver function tests (LFTs), hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis C antibody, full blood count (FBC), and urine for drug screening. Consider HIV testing if at risk but it is usually better arranged at a later stage. 4. Prescribing may be considered for a variety of drugs but objectives will differ according to drug type and individual. 5. In the case of opioid users, prescribing may be useful to stabilize their lives and to promote attendance for professional help. It may reduce high risk behaviour for contracting and spreading HIV. 6. If medication is given to opioid users, methadone mixture 1 mg/ml given once a day is the prescription of choice. Dispensing should be on a daily basis and the blue prescription form FP10 (MDA) allows the chemist to dispense daily for up to 14 days. A maximum ceiling of 100 mg methadone/day should not be exceeded. The initial dose will depend on the amount of opioid consumed in the previous week.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1345155

  4. Dry fermentation of agricultural residues

    NASA Astrophysics Data System (ADS)

    Jewell, W. J.; Chandler, J. A.; Dellorto, S.; Fanfoni, K. J.; Fast, S.; Jackson, D.; Kabrick, R. M.

    1981-09-01

    A dry fermentation process is discussed which converts agricultural residues to methane, using the residues in their as produced state. The process appears to simplify and enhance the possibilities for using crop residues as an energy source. The major process variables investigated include temperature, the amount and type of inoculum, buffer requirements, compaction, and pretreatment to control the initial available organic components that create pH problems. A pilot-scale reactor operation on corn stover at a temperature of 550 C, with 25 percent initial total solids, a seed-to-feed ratio of 2.5 percent, and a buffer-to-feed ratio of 8 percent achieved 33 percent total volatile solids destruction in 60 days. Volumetric biogas yields from this unit were greater than 1 vol/vol day for 12 days, and greater than 0.5 vol/vol day for 32 days, at a substrate density of 169 kg/m (3).

  5. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Recent developments on new anti-HIV agents and drugs for opportunistic infections are highlighted. Information is provided on the infusion inhibitor T-20; DuPont's second generation non-nukes, DPC 961 and DPC 963; Papirine (PEN203) for the human papilloma virus; Sporanox for treating fungal infections; and the antiretroviral protein, lysozyme. In addition, information is given on a plant found in the Bolivian rainforest that may contain compounds to prevent HIV infection by blocking the enzyme, integrase. Other promising new drugs addressed at the 6th Conference on Retroviruses and Opportunistic Infections are listed in a table. Contact information for US clinical trials is provided.

  6. Drug Allergy.

    PubMed

    Waheed, Abdul; Hill, Tiffany; Dhawan, Nidhi

    2016-09-01

    An adverse drug reaction relates to an undesired response to administration of a drug. Type A reactions are common and are predictable to administration, dose response, or interaction with other medications. Type B reactions are uncommon with occurrences that are not predictable. Appropriate diagnosis, classification, and entry into the chart are important to avoid future problems. The diagnosis is made with careful history, physical examination, and possibly allergy testing. It is recommended that help from allergy immunology specialists should be sought where necessary and that routine prescription of Epi pen should be given to patients with multiple allergy syndromes. PMID:27545730

  7. [Ureter drugs].

    PubMed

    Raynal, G; Bellan, J; Saint, F; Tillou, X; Petit, J

    2008-03-01

    Many improvements have been made recently in the field of the ureteral smooth muscle pharmacology. After a brief summary on physiological basis, we review what is known about effects on ureter of different drugs class. In a second part, we review clinical applications for renal colic analgesia, calculi expulsive medical therapy, ESWL adjuvant treatment and preoperative treatment before retrograde access. There are now sufficient data on NSAID and alpha-blockers. beta-agonists, especially for beta3 selective ones, and topical drugs before retrograde access are interesting and should be further evaluated.

  8. Residual contact restraints in cryogenics

    NASA Astrophysics Data System (ADS)

    Cretegny, J. F.; Demonicault, J. M.

    The use of residual stress measurements to evaluate the state of cryogenic turbomachines, whose surfaces are worn by the working conductions in dry contact, is addressed. Their contribution to the understanding of the reasons of possible ruptures is considered. It is stated that residual stress measurements should be used as a complementary tool rather than as input data for models. It is shown, thanks to two examples concerning the ball bearings and splines of the liquid hydrogen turbopump of the Vulcain engine, what can be expected from such techniques. Total exploitation of the results has still to be done, but preliminary results are quite encouraging.

  9. Collection of sugarcane crop residue for energy

    SciTech Connect

    Eiland, B.R.; Clayton, J.E.

    1982-12-01

    Crop residue left after sugarcane harvesting was recovered using a forage harvester and a large round baler. The quantity, bulk density and moisture content of the crop residue was determined in four fields. Crop residue from 7 ha was burned in boilers at a sugar mill. Samples of this residue were tested by a laboratory and compared to sugarcane bagasse.

  10. 76 FR 51038 - Guidance for Industry on Residual Drug in Transdermal and Related Drug Delivery Systems...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-17

    ... during product design and development--as well as during manufacturing and product life-cycle management... development--as well as during manufacturing and product life-cycle management--to ensure that the amount of... August 3, 2010 (75 FR 45640), FDA announced the availability of the draft version of this guidance....

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

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-05

    ....0 ppm. (2) Chickens and turkeys--(i) Liver and kidney: 1 ppm. (ii) Muscle: 0.5 ppm. (iii) Eggs: (A...): 0.4 ppm. (ii) Liver: 2 ppm. (iii) Muscle: 1 ppm. (iv) Milk: 0.1 ppm. (2) Chickens and turkeys...) Liver: 6 ppm. (ii) Kidney and fat: 12 ppm. (iii) Muscle: 2 ppm. (2) Chickens, turkeys, and...

  12. Anthelmintics residues in raw milk. Assessing intake by a children population.

    PubMed

    Tsiboukis, D; Sazakli, E; Jelastopulu, E; Leotsinidis, M

    2013-01-01

    Anthelmintics, such as benzimidazoles and probenzimidazoles, are veterinary drugs used against endoparasites in food producing animals. A number of these drugs are considered responsible for embryotoxicity and teratogenicity. The residue levels of Albendazole, Febantel, Fenbendazole, Mebendazole and some of their metabolites (Albendazole sulphoxide, Albendazole sulphone, Fenbendazole sulfone) were assessed in 123 (42 goat, 69 sheep, 12 bovine) raw milk samples collected from all farms throughout Southern Greece. Sample analysis was performed by HPLC with Diode Array Detector. A high percentage (27.6%) of the samples examined was found to be positive for the investigated compounds. In 14 samples (11.4%), the residues' concentration exceeded the established Maximum Residue Limits. Estimated Daily Intakes were calculated for a population of 723 children aged 10-12 years. Data on milk consumption were obtained by personal interview through a 7-day food frequency questionnaire. The maximum Estimated Daily Intakes for the anthelmintic residues, concerning raw milk, did not exceed the current Acceptable Daily Intake.

  13. Antineoplastic Drugs.

    ERIC Educational Resources Information Center

    Morris, Sara; Michael, Nancy, Ed.

    This module on antineoplastic drugs is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  14. Potential hazards of fumigant residues.

    PubMed Central

    Fishbein, L

    1976-01-01

    A spectrum of fumigants (primarily ethylene dibromide, 1,2-dibromo-3-chloropropane, ethylene oxide, symdibromotetetrachloroethane, 1,3-dichloropropene, dichlorovos, carbon tetrachloride, methyl bromide) as well as their degradation products in foodstuffs and soil have been examined mainly in regard to the potential mutagenicity of their residues. PMID:789068

  15. Solidification process for sludge residue

    SciTech Connect

    Pearce, K.L.

    1998-09-10

    This report investigates the solidification process used at 100-N Basin to solidify the N Basin sediment and assesses the N Basin process for application to the K Basin sludge residue material. This report also includes a discussion of a solidification process for stabilizing filters. The solidified matrix must be compatible with the Environmental Remediation Disposal Facility acceptance criteria.

  16. Leptogenesis and residual CP symmetry

    NASA Astrophysics Data System (ADS)

    Chen, Peng; Ding, Gui-Jun; King, Stephen F.

    2016-03-01

    We discuss flavour dependent leptogenesis in the framework of lepton flavour models based on discrete flavour and CP symmetries applied to the type-I seesaw model. Working in the flavour basis, we analyse the case of two general residual CP symmetries in the neutrino sector, which corresponds to all possible semi-direct models based on a preserved Z 2 in the neutrino sector, together with a CP symmetry, which constrains the PMNS matrix up to a single free parameter which may be fixed by the reactor angle. We systematically study and classify this case for all possible residual CP symmetries, and show that the R-matrix is tightly constrained up to a single free parameter, with only certain forms being consistent with successful leptogenesis, leading to possible connections between leptogenesis and PMNS parameters. The formalism is completely general in the sense that the two residual CP symmetries could result from any high energy discrete flavour theory which respects any CP symmetry. As a simple example, we apply the formalism to a high energy S 4 flavour symmetry with a generalized CP symmetry, broken to two residual CP symmetries in the neutrino sector, recovering familiar results for PMNS predictions, together with new results for flavour dependent leptogenesis.

  17. Caspase-3 binds diverse P4 residues in peptides as revealed by crystallography and structural modeling.

    SciTech Connect

    Fang, Bin; Fu, Guoxing; Agniswamy, Johnson; Harrison, Robert W.; Weber, Irene T.

    2009-03-31

    Caspase-3 recognition of various P4 residues in its numerous protein substrates was investigated by crystallography, kinetics, and calculations on model complexes. Asp is the most frequent P4 residue in peptide substrates, although a wide variety of P4 residues are found in the cellular proteins cleaved by caspase-3. The binding of peptidic inhibitors with hydrophobic P4 residues, or no P4 residue, is illustrated by crystal structures of caspase-3 complexes with Ac-IEPD-Cho, Ac-WEHD-Cho, Ac-YVAD-Cho, and Boc-D(OMe)-Fmk at resolutions of 1.9-2.6 {angstrom}. The P4 residues formed favorable hydrophobic interactions in two separate hydrophobic regions of the binding site. The side chains of P4 Ile and Tyr form hydrophobic interactions with caspase-3 residues Trp206 and Trp214 within a non-polar pocket of the S4 subsite, while P4 Trp interacts with Phe250 and Phe252 that can also form the S5 subsite. These interactions of hydrophobic P4 residues are distinct from those for polar P4 Asp, which indicates the adaptability of caspase-3 for binding diverse P4 residues. The predicted trends in peptide binding from molecular models had high correlation with experimental values for peptide inhibitors. Analysis of structural models for the binding of 20 different amino acids at P4 in the aldehyde peptide Ac-XEVD-Cho suggested that the majority of hydrophilic P4 residues interact with Phe250, while hydrophobic residues interact with Trp206, Phe250, and Trp214. Overall, the S4 pocket of caspase-3 exhibits flexible adaptation for different residues and the new structures and models, especially for hydrophobic P4 residues, will be helpful for the design of caspase-3 based drugs.

  18. 75 FR 24394 - Animal Drugs, Feeds, and Related Products; Withdrawal of Approval of a New Animal Drug...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-05

    ... medicated article was voluntarily withdrawn (60 FR 37651, July 21, 1995) and approved conditions of use for... NADA 45-738, were removed (60 FR 39847, July 21, 1995). At this time, the tolerances for residues of... HUMAN SERVICES Food and Drug Administration 21 CFR Parts 556 and 558 Animal Drugs, Feeds, and...

  19. Therapeutic drug monitoring: antiarrhythmic drugs.

    PubMed

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents.

  20. Therapeutic drug monitoring: antiarrhythmic drugs

    PubMed Central

    Campbell, T J; Williams, K M

    2001-01-01

    Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. These agents have a very significant toxicity, and while they are being used less, therapeutic drug monitoring (TDM) does significantly increase the safety with which they can be administered. Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers. These are generally safe agents which do not normally require TDM. Class III antiarrhythmic agents include sotalol and amiodarone. TDM can be useful in the case of amiodarone to monitor compliance and toxicity but is generally of little value for sotalol. Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. These are normally monitored by haemodynamic effects, rather than using TDM. Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline. TDM is very useful for monitoring the administration (and particularly the safety) of both of these agents. PMID:11564050

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

    PubMed

    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.

  2. 40 CFR 1065.705 - Residual and intermediate residual fuel.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... specifications for fuels meeting the definition of residual fuel in 40 CFR 80.2, including fuels marketed as... by reference in § 1065.1010). (2) Phosphorus is at or below 15 mg per kg of fuel based on the... 0.15 ISO 6245. Water, max (m3/m3) % 0.5 0.5 0.5 0.5 0.5 ISO 3733. Sulfur, max (kg/kg) % 3.50 4.00...

  3. 40 CFR 1065.705 - Residual and intermediate residual fuel.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... specifications for fuels meeting the definition of residual fuel in 40 CFR 80.2, including fuels marketed as... ISO 6245. Water, max (m3/m3)% 0.5 0.5 0.5 0.5 0.5 ISO 3733. Sulfur, max (kg/kg)% 3.50 4.00 4.50 4.50 4... the elements zinc, phosphorus, or calcium is at or below the specified limits. We consider a fuel...

  4. 40 CFR 1065.705 - Residual and intermediate residual fuel.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... specifications for fuels meeting the definition of residual fuel in 40 CFR 80.2, including fuels marketed as... ISO 6245. Water, max (m3/m3)% 0.5 0.5 0.5 0.5 0.5 ISO 3733. Sulfur, max (kg/kg)% 3.50 4.00 4.50 4.50 4... the elements zinc, phosphorus, or calcium is at or below the specified limits. We consider a fuel...

  5. Drug watch.

    PubMed

    Whitson, S

    1999-01-01

    Current research findings and treatment issues related to a number of drugs are briefly outlined. Topics include T-20, a reformulation of ddI, PMPA, chicoric acid, Omniferon (alpha leukoferon), and Mepron. Also discussed is a non-nucleoside reverse transcriptase inhibitor called calanolide A, which is synthesized from a tree native to Malaysian rain forests. An update is provided on Panretin, a gel which is used to treat KS lesions. Contact information is provided.

  6. Residue depletion of albendazole and its metabolites in aquacultured yellow perch (Perca flavescens).

    PubMed

    Yu, D; Evans, E R; Hasbrouck, N; Reimschuessel, R; Shaikh, B

    2012-12-01

    Metabolism and residue depletion studies are conducted to determine the marker residue (MR) of a drug in a target tissue of food animals. The MR is used to monitor potential unauthorized use of drugs. The current work is a continuation of our efforts to study metabolism and depletion profiles of albendazole in multiple finfish species to determine a common MR. The results of this study suggest that albendazole sulfone metabolite could potentially serve as MR for albendazole in yellow perch muscle, similar to channel catfish and hybrid striped bass as reported previously by us. PMID:22150530

  7. Catalytic combustion of residual fuels

    NASA Technical Reports Server (NTRS)

    Bulzan, D. L.; Tacina, R. R.

    1981-01-01

    A noble metal catalytic reactor was tested using two grades of petroleum derived residual fuels at specified inlet air temperatures, pressures, and reference velocities. Combustion efficiencies greater than 99.5 percent were obtained. Steady state operation of the catalytic reactor required inlet air temperatures of at least 800 K. At lower inlet air temperatures, upstream burning in the premixing zone occurred which was probably caused by fuel deposition and accumulation on the premixing zone walls. Increasing the inlet air temperature prevented this occurrence. Both residual fuels contained about 0.5 percent nitrogen by weight. NO sub x emissions ranged from 50 to 110 ppm by volume at 15 percent excess O2. Conversion of fuel-bound nitrogen to NO sub x ranged from 25 to 50 percent.

  8. Pesticidal residues in animal tissues

    USGS Publications Warehouse

    DeWitt, J.B.; Menzie, C.M.; Adomaitis, V.A.; Reichel, W.L.

    1960-01-01

    Tests with penned starlings, rats, pheasants, and ducks indicated that each species differs in sensitivity to the various pesticides. Residues in tissues are proportional to the degree of exposure during area treatment and they are also found in animals shot six or more months after treatment. The presence of more than 20-30 ppm of DDT, 20 ppm of chlordan, and 6-20 ppm of heptachlor epoxide in quail tissues indicated that the birds had ingested lethal dosages of the pesticides.

  9. Calcination/dissolution residue treatment

    SciTech Connect

    Knight, R.C.; Creed, R.F.; Patello, G.K.; Hollenberg, G.W.; Buehler, M.F.; O`Rourke, S.M.; Visnapuu, A.; McLaughlin, D.F.

    1994-09-01

    Currently, high-level wastes are stored underground in steel-lined tanks at the Hanford site. Current plans call for the chemical pretreatment of these wastes before their immobilization in stable glass waste forms. One candidate pretreatment approach, calcination/dissolution, performs an alkaline fusion of the waste and creates a high-level/low-level partition based on the aqueous solubilities of the components of the product calcine. Literature and laboratory studies were conducted with the goal of finding a residue treatment technology that would decrease the quantity of high-level waste glass required following calcination/dissolution waste processing. Four elements, Fe, Ni, Bi, and U, postulated to be present in the high-level residue fraction were identified as being key to the quantity of high-level glass formed. Laboratory tests of the candidate technologies with simulant high-level residues showed reductive roasting followed by carbonyl volatilization to be successful in removing Fe, Ni, and Bi. Subsequent bench-scale tests on residues from calcination/dissolution processing of genuine Hanford Site tank waste showed Fe was separated with radioelement decontamination factors of 70 to 1,000 times with respect to total alpha activity. Thermodynamic analyses of the calcination of five typical Hanford Site tank waste compositions also were performed. The analyses showed sodium hydroxide to be the sole molten component in the waste calcine and emphasized the requirement for waste blending if fluid calcines are to be achieved. Other calcine phases identified in the thermodynamic analysis indicate the significant thermal reconstitution accomplished in calcination.

  10. Residue management at Rocky Flats

    SciTech Connect

    Olencz, J.

    1995-12-31

    Past plutonium production and manufacturing operations conducted at the Rocky Flats Environmental Technology Site (RFETS) produced a variety of plutonium-contaminated by-product materials. Residues are a category of these materials and were categorized as {open_quotes}materials in-process{close_quotes} to be recovered due to their inherent plutonium concentrations. In 1989 all RFETS plutonium production and manufacturing operations were curtailed. This report describes the management of plutonium bearing liquid and solid wastes.

  11. Residue gasification tests at TVA

    SciTech Connect

    Spencer, D.

    1984-11-01

    The Texaco gasification process was identified as an attractive way to utilise vacuum bottoms from the Exxon Donor Solvent liquefaction process to generate synthesis gas. This gas can then be upgraded to produce the hydrogen required by the EDS plant. Gasification tests were carried out at TVA's 200 t/day Muscle Shoals plant and are reported here. As a result, Texaco expects that a plant could be designed to handle EDS residue from any high-rank coal.

  12. Drug Rash (Unclassified Drug Eruption) in Children

    MedlinePlus

    ... rash and rashes clinical tools newsletter | contact Share | Drug Eruption, Unclassified (Pediatric) A parent's guide to condition ... lesions coming together into larger lesions typical of drug rashes (eruptions). Overview A drug eruption, also known ...

  13. Asthma - control drugs

    MedlinePlus

    Asthma - inhaled corticosteroids; Asthma - long-acting beta-agonists; Asthma - leukotriene modifiers; Asthma - cromolyn; Bronchial asthma-control drugs; Wheezing - control drugs; Reactive airway disease - control drugs

  14. Geotechnical characteristics of residual soils

    SciTech Connect

    Townsend, F.C.

    1985-01-01

    Residual soils are products of chemical weathering and thus their characteristics are dependent upon environmental factors of climate, parent material, topography and drainage, and age. These conditions are optimized in the tropics where well-drained regions produce reddish lateritic soils rich in iron and aluminum sesquioxides and kaolinitic clays. Conversely, poorly drained areas tend towards montmorillonitic expansive black clays. Andosols develop over volcanic ash and rock regions and are rich in allophane (amorphous silica) and metastable halloysite. The geological origins greatly affect the resulting engineering characteristics. Both lateritic soils and andosols are susceptible to property changes upon drying, and exhibit compaction and strength properties not indicative of their classification limits. Both soils have been used successfully in earth dam construction, but attention must be given to seepage control through the weathered rock. Conversely, black soils are unpopular for embankments. Lateritic soils respond to cement stabilization and, in some cases, lime stabilization. Andosols should also respond to lime treatment and cement treatments if proper mixing can be achieved. Black expansive residual soils respond to lime treatment by demonstrating strength gains and decreased expansiveness. Rainfall induced landslides are typical of residual soil deposits.

  15. Evaluation of residue drum storage safety risks

    SciTech Connect

    Conner, W.V.

    1994-06-17

    A study was conducted to determine if any potential safety problems exist in the residue drum backlog at the Rocky Flats Plant. Plutonium residues stored in 55-gallon drums were packaged for short-term storage until the residues could be processed for plutonium recovery. These residues have now been determined by the Department of Energy to be waste materials, and the residues will remain in storage until plans for disposal of the material can be developed. The packaging configurations which were safe for short-term storage may not be safe for long-term storage. Interviews with Rocky Flats personnel involved with packaging the residues reveal that more than one packaging configuration was used for some of the residues. A tabulation of packaging configurations was developed based on the information obtained from the interviews. A number of potential safety problems were identified during this study, including hydrogen generation from some residues and residue packaging materials, contamination containment loss, metal residue packaging container corrosion, and pyrophoric plutonium compound formation. Risk factors were developed for evaluating the risk potential of the various residue categories, and the residues in storage at Rocky Flats were ranked by risk potential. Preliminary drum head space gas sampling studies have demonstrated the potential for formation of flammable hydrogen-oxygen mixtures in some residue drums.

  16. Subcutaneous implants for long-acting drug therapy in laboratory animals may generate unintended drug reservoirs

    PubMed Central

    Guarnieri, Michael; Tyler, Betty M.; DeTolla, Louis; Zhao, Ming; Kobrin, Barry

    2014-01-01

    Background: Long-acting therapy in laboratory animals offers advantages over the current practice of 2-3 daily drug injections. Yet little is known about the disintegration of biodegradable drug implants in rodents. Objective: Compare bioavailability of buprenorphine with the biodegradation of lipid-encapsulated subcutaneous drug pellets. Methods: Pharmacokinetic and histopathology studies were conducted in BALB/c female mice implanted with cholesterol-buprenorphine drug pellets. Results: Drug levels are below the level of detection (0.5 ng/mL plasma) within 4-5 days of implant. However, necroscopy revealed that interstitial tissues begin to seal implants within a week. Visual inspection of the implant site revealed no evidence of inflammation or edema associated with the cholesterol-drug residue. Chemical analyses demonstrated that the residues contained 10-13% of the initial opiate dose for at least two weeks post implant. Discussion: The results demonstrate that biodegradable scaffolds can become sequestered in the subcutaneous space. Conclusion: Drug implants can retain significant and unintended reservoirs of drugs. PMID:24459402

  17. A method for the separation of residues of nine compounds in cattle liver related to treatment with oxfendazole.

    PubMed

    Rose, M D

    1999-07-01

    A method for the determination of nine compounds closely related to oxfendazole has been developed for the monitoring of residues in food. The method is based on a multi-residue procedure for basic drug residues and used strong cation exchange solid phase extraction for sample clean-up. These nine compounds include fenbendazole, which is itself a licensed veterinary product. The pro-drug febantel converts quickly to fenbendazole or oxfendazole soon after administration. The method is therefore suitable for monitoring residues following the use of any of these compounds. Some of these analytes have been shown to be present as residues following the treatment of farm animals with oxfendazole. Average recoveries for the nine compounds from tissue fortified with 100 micrograms kg-1 were between 34% and 96% with relative standard deviations between 3% and 22%.

  18. Veterinary drugs: disposition, biotransformation and risk evaluation.

    PubMed

    Fink-Gremmels, J; van Miert, A S

    1994-12-01

    Veterinary drugs may only be produced, distributed and administered after being licensed. This implies that, prior to marketing, a critical evaluation of the pharmaceutical quality, the clinical efficacy and the over-all pharmacological and toxicological properties of the active substances will be performed by national and/or supranational authorities. However, despite a sophisticated legal (harmonized) framework, a number of factors involved in residue formation and safety assessment remain unpredictable or dependant on the current 'state of the art' in the understanding of molecular pharmacology and toxicology. For example, drug disposition and residue formation in the target animal species may be influenced by a broad variety of physiological parameters including age, sex and diet, as well as by pathological conditions especially the acute phase response to infection. These factors affect both drug disposition and metabolite formation. Furthermore, current thinking in toxicological risk assessment is influenced by recent developments in molecular toxicology and thus by an increased but still incomplete understanding of the interaction of a toxic compound with the living organism. General recognized principles in the evaluation of potential toxicants are applied in the recommendation of withdrawal times and the establishment of maximum residue limits (MRL values). Apart from toxicological-based assessment, increasing awareness is directed to other than toxicological responses, especially the potential risk of effects of antimicrobial residues on human gastrointestinal microflora. Thus, the methodology of risk assessment is discussed in the context of the recently established legal framework within the European Union.

  19. Egg residue considerations during the treatment of backyard poultry.

    PubMed

    Marmulak, Tara; Tell, Lisa A; Gehring, Ronette; Baynes, Ronald E; Vickroy, Thomas W; Riviere, Jim E

    2015-12-15

    The purpose of this digest was to provide US veterinarians guidance on the responsible treatment of backyard poultry flocks. The treatment of backyard poultry can be a daunting task for veterinarians because only limited resources are available; however, it is likely to become an increasingly common task owing to the increasing popularity of backyard poultry throughout the United States, especially in urban and suburban areas. Although backyard poultry flock owners may consider their birds pets, the FDA considers them food-producing animals, and veterinarians should follow all regulations that pertain to food-producing animals when administering or prescribing drugs to those birds. The lack of FDA-approved drugs for use in laying hens frequently necessitates the use of drugs in an extralabel manner in backyard poultry. Unfortunately, information regarding the depletion of drug residues in eggs from hens treated with various drugs in an extralabel manner is sparse or lacking, and veterinarians need to be cognizant of this issue, especially when the eggs from treated hens are intended for human consumption.

  20. Egg residue considerations during the treatment of backyard poultry.

    PubMed

    Marmulak, Tara; Tell, Lisa A; Gehring, Ronette; Baynes, Ronald E; Vickroy, Thomas W; Riviere, Jim E

    2015-12-15

    The purpose of this digest was to provide US veterinarians guidance on the responsible treatment of backyard poultry flocks. The treatment of backyard poultry can be a daunting task for veterinarians because only limited resources are available; however, it is likely to become an increasingly common task owing to the increasing popularity of backyard poultry throughout the United States, especially in urban and suburban areas. Although backyard poultry flock owners may consider their birds pets, the FDA considers them food-producing animals, and veterinarians should follow all regulations that pertain to food-producing animals when administering or prescribing drugs to those birds. The lack of FDA-approved drugs for use in laying hens frequently necessitates the use of drugs in an extralabel manner in backyard poultry. Unfortunately, information regarding the depletion of drug residues in eggs from hens treated with various drugs in an extralabel manner is sparse or lacking, and veterinarians need to be cognizant of this issue, especially when the eggs from treated hens are intended for human consumption. PMID:26642132

  1. Antiplatelet Drugs

    PubMed Central

    Hirsh, Jack; Spencer, Frederick A.; Baglin, Trevor P.; Weitz, Jeffrey I.

    2012-01-01

    The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment. PMID:22315278

  2. PESTICIDE RESIDUE RECOVERIES FROM SURFACE WIPES

    EPA Science Inventory

    Human exposure is a consequence of pesticide use indoors with a primary source resulting from residue deposition on household surfaces. Accurate measurements of surface residues is essential for estimating exposure from different routes. Various procedures have been developed ...

  3. 48 CFR 970.5001 - Residual powers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Residual powers. 970.5001 Section 970.5001 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY....5001 Residual powers....

  4. 48 CFR 250.104 - Residual powers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Residual powers. 250.104 Section 250.104 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT... Contractual Actions 250.104 Residual powers....

  5. 48 CFR 970.5001 - Residual powers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Residual powers. 970.5001 Section 970.5001 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY....5001 Residual powers....

  6. 48 CFR 250.104 - Residual powers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 3 2011-10-01 2011-10-01 false Residual powers. 250.104 Section 250.104 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT... Contractual Actions 250.104 Residual powers....

  7. 48 CFR 970.5001 - Residual powers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Residual powers. 970.5001 Section 970.5001 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY....5001 Residual powers....

  8. 48 CFR 1850.104 - Residual powers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Residual powers. 1850.104 Section 1850.104 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION... 1850.104 Residual powers....

  9. 48 CFR 1850.104 - Residual powers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Residual powers. 1850.104 Section 1850.104 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION... 1850.104 Residual powers....

  10. 48 CFR 1850.104 - Residual powers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Residual powers. 1850.104 Section 1850.104 Federal Acquisition Regulations System NATIONAL AERONAUTICS AND SPACE ADMINISTRATION... 1850.104 Residual powers....

  11. 48 CFR 250.104 - Residual powers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 3 2014-10-01 2014-10-01 false Residual powers. 250.104 Section 250.104 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT... Contractual Actions 250.104 Residual powers....

  12. 48 CFR 970.5001 - Residual powers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Residual powers. 970.5001 Section 970.5001 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY....5001 Residual powers....

  13. 48 CFR 250.104 - Residual powers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 3 2012-10-01 2012-10-01 false Residual powers. 250.104 Section 250.104 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT... Contractual Actions 250.104 Residual powers....

  14. 48 CFR 970.5001 - Residual powers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Residual powers. 970.5001 Section 970.5001 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY....5001 Residual powers....

  15. 48 CFR 250.104 - Residual powers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 3 2013-10-01 2013-10-01 false Residual powers. 250.104 Section 250.104 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS SYSTEM, DEPARTMENT... Contractual Actions 250.104 Residual powers....

  16. Drugs Approved for Neuroblastoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for neuroblastoma. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  17. Drugs Approved for Retinoblastoma

    Cancer.gov

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for retinoblastoma. The list includes generic names and brand names. The drug names link to NCI’s Cancer Drug Information summaries.

  18. Drugs Approved for Leukemia

    Cancer.gov

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  19. Drug Plan Coverage Rules

    MedlinePlus

    ... works with other insurance Find health & drug plans Drug plan coverage rules Note Call your Medicare drug ... shingles vaccine) when medically necessary to prevent illness. Drugs you get in hospital outpatient settings In most ...

  20. Therapeutic Drug Monitoring

    MedlinePlus

    ... be limited. Home Visit Global Sites Search Help? Therapeutic Drug Monitoring Share this page: Was this page ... Monitored Drugs | Common Questions | Related Pages What is therapeutic drug monitoring? Therapeutic drug monitoring is the measurement ...

  1. [Drug poisoning].

    PubMed

    Gainza, I; Nogué, S; Martínez Velasco, C; Hoffman, R S; Burillo-Putze, G; Dueñas, A; Gómez, J; Pinillos, M A

    2003-01-01

    A review is made of acute poisoning by opiates and its treatment in the emergency services, bearing in mind the progressive decline in the number of cases presented with the arrival of new forms of their administration, as well as the presence of new addictive drugs that have resulted in a shift in consumption habits. Reference is also made to the way in which the different types of existing substances originated, with the aim of achieving a better understanding of their use and in order to administer the most suitable treatment when poisoning occurs. Cocaine poisoning is discussed, with reference to its clinical picture, diagnosis and treatment. The consumption of illegal drugs in our country has undergone a notable change in recent years, with heroin being relegated and the incorporation of cocaine, amphetamine derivatives such as "ecstasy" (MDMA), "liquid ecstasy" (GHB) and, to a lesser extent, ketamine. A review is made of cannabis and its derivates, from the history of its consumption and the preparations employed to the effects produced in the different bodily systems. A brief explanation is also given of its metabolites and its principal mechanisms of action. Finally, we comment on the effects of LSD and hallucinogenic mushrooms.

  2. 48 CFR 50.104 - Residual powers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Residual powers. 50.104... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.104 Residual powers. This section prescribes standards and procedures for exercising residual powers under Pub. L....

  3. 9 CFR 311.39 - Biological residues.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 2 2014-01-01 2014-01-01 false Biological residues. 311.39 Section... Biological residues. Carcasses, organs, or other parts of carcasses of livestock shall be condemned if it is determined that they are adulterated because of the presence of any biological residues....

  4. 9 CFR 311.39 - Biological residues.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 2 2012-01-01 2012-01-01 false Biological residues. 311.39 Section... Biological residues. Carcasses, organs, or other parts of carcasses of livestock shall be condemned if it is determined that they are adulterated because of the presence of any biological residues....

  5. 9 CFR 311.39 - Biological residues.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 2 2013-01-01 2013-01-01 false Biological residues. 311.39 Section... Biological residues. Carcasses, organs, or other parts of carcasses of livestock shall be condemned if it is determined that they are adulterated because of the presence of any biological residues....

  6. 9 CFR 311.39 - Biological residues.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 2 2011-01-01 2011-01-01 false Biological residues. 311.39 Section... Biological residues. Carcasses, organs, or other parts of carcasses of livestock shall be condemned if it is determined that they are adulterated because of the presence of any biological residues....

  7. 48 CFR 50.104 - Residual powers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Residual powers. 50.104... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.104 Residual powers. This section prescribes standards and procedures for exercising residual powers under Pub. L....

  8. 48 CFR 50.104 - Residual powers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Residual powers. 50.104... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.104 Residual powers. This section prescribes standards and procedures for exercising residual powers under Pub. L....

  9. 48 CFR 50.104 - Residual powers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Residual powers. 50.104... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.104 Residual powers. This section prescribes standards and procedures for exercising residual powers under Pub. L....

  10. 48 CFR 50.104 - Residual powers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Residual powers. 50.104... EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 50.104 Residual powers. This section prescribes standards and procedures for exercising residual powers under Pub. L....

  11. Quantitation of the residual DNA from rice-derived recombinant human serum albumin.

    PubMed

    Chen, Zhen; Dai, Huixia; Liu, Zhenwei; Zhang, Liping; Pang, Jianlei; Ou, Jiquan; Yang, Daichang

    2014-04-01

    Residual DNA in recombinant protein pharmaceuticals can potentially cause safety issues in clinical applications; thus, maximum residual limit has been established by drug safety authorities. Assays for residual DNA in Escherichia coli, yeast, and Chinese hamster ovary (CHO) cell expression systems have been established, but no rice residual DNA assay for rice expression systems has been designed. To develop an assay for the quantification of residual DNA that is produced from rice seed, we established a sensitive assay using quantitative real-time polymerase chain reaction (qPCR) based on the 5S ribosomal RNA (rRNA) genes. We found that a 40-cycle qPCR exhibited a linear response when the template concentration was in the range of 2×10(4) to 0.2pg of DNA per reaction in TaqMan and SYBR Green I assays. The amplification efficiency was 103 to 104%, and the amount of residual DNA from recombinant human serum albumin from Oryza sativa (OsrHSA) was less than 3.8ng per dosage, which was lower than that recommended by the World Health Organization (WHO). Our results indicate that the current purification protocol could efficiently remove residual DNA during manufacturing and processing. Furthermore, this protocol could be viable in other cereal crop endosperm expression systems for developing a residual DNA quantitation assay using the highly conserved 5S rRNA gene of the crops.

  12. Quantitation of the residual DNA from rice-derived recombinant human serum albumin.

    PubMed

    Chen, Zhen; Dai, Huixia; Liu, Zhenwei; Zhang, Liping; Pang, Jianlei; Ou, Jiquan; Yang, Daichang

    2014-04-01

    Residual DNA in recombinant protein pharmaceuticals can potentially cause safety issues in clinical applications; thus, maximum residual limit has been established by drug safety authorities. Assays for residual DNA in Escherichia coli, yeast, and Chinese hamster ovary (CHO) cell expression systems have been established, but no rice residual DNA assay for rice expression systems has been designed. To develop an assay for the quantification of residual DNA that is produced from rice seed, we established a sensitive assay using quantitative real-time polymerase chain reaction (qPCR) based on the 5S ribosomal RNA (rRNA) genes. We found that a 40-cycle qPCR exhibited a linear response when the template concentration was in the range of 2×10(4) to 0.2pg of DNA per reaction in TaqMan and SYBR Green I assays. The amplification efficiency was 103 to 104%, and the amount of residual DNA from recombinant human serum albumin from Oryza sativa (OsrHSA) was less than 3.8ng per dosage, which was lower than that recommended by the World Health Organization (WHO). Our results indicate that the current purification protocol could efficiently remove residual DNA during manufacturing and processing. Furthermore, this protocol could be viable in other cereal crop endosperm expression systems for developing a residual DNA quantitation assay using the highly conserved 5S rRNA gene of the crops. PMID:24388867

  13. Drugs and the Brain.

    ERIC Educational Resources Information Center

    National Institutes of Health (DHHS), Bethesda, MD.

    This booklet explores various aspects of drug addiction, with a special focus on drugs' effects on the brain. A brief introduction presents information on the rampant use of drugs in society and elaborates the distinction between drug abuse and drug addiction. Next, a detailed analysis of the brain and its functions is given. Drugs target the more…

  14. Process to recycle shredder residue

    DOEpatents

    Jody, Bassam J.; Daniels, Edward J.; Bonsignore, Patrick V.

    2001-01-01

    A system and process for recycling shredder residue, in which separating any polyurethane foam materials are first separated. Then separate a fines fraction of less than about 1/4 inch leaving a plastics-rich fraction. Thereafter, the plastics rich fraction is sequentially contacted with a series of solvents beginning with one or more of hexane or an alcohol to remove automotive fluids; acetone to remove ABS; one or more of EDC, THF or a ketone having a boiling point of not greater than about 125.degree. C. to remove PVC; and one or more of xylene or toluene to remove polypropylene and polyethylene. The solvents are recovered and recycled.

  15. Automating a residual gas analyzer

    NASA Technical Reports Server (NTRS)

    Petrie, W. F.; Westfall, A. H.

    1982-01-01

    A residual gas analyzer (RGA), a device for measuring the amounts and species of various gases present in a vacuum system is discussed. In a recent update of the RGA, it was shown that the use of microprocessors could revolutionize data acquisition and data reduction. This revolution is exemplified by the Inficon 1Q200 RGA which was selected to meet the needs of this update. The Inficon RGA and the Zilog microcomputer were interfaced in order the receive and format the digital data from the RGA. This automated approach is discussed in detail.

  16. Fiber-optic polymer residue monitor

    SciTech Connect

    Pfeifer, K.B.; Jarecki, R.L. Jr.; Dalton, T.J.

    1998-10-01

    Semiconductor processing tools that use a plasma to etch polysilicon or oxides produce residue polymers that build up on the exposed surfaces of the processing chamber. These residues are generally stressed and with time can cause flaking onto wafers resulting in yield loss. Currently, residue buildup is not monitored, and chambers are cleaned at regular intervals resulting in excess downtime for the tool. In addition, knowledge of the residue buildup rate and index of refraction is useful in determining the state of health of the chamber process. The authors have developed a novel optical fiber-based robust sensor that allows measurement of the residue polymer buildup while not affecting the plasma process.

  17. Managing residual limb hyperhidrosis in wounded warriors.

    PubMed

    Pace, Sarah; Kentosh, Joshua

    2016-06-01

    Residual limb dermatologic problems are a common concern among young active traumatic amputee patients who strive to maintain an active lifestyle. Hyperhidrosis of residual limbs is a recognized inciting factor that often contributes to residual limb dermatoses and is driven by the design of the prosthetic liner covering the residual limb. Treatment of hyperhidrosis in this population presents a unique challenge. Several accepted treatments of hyperhidrosis can offer some relief but have been limited by lack of results or side-effect profiles. Microwave thermal ablation has presented an enticing potential for residual limb hyperhidrosis. PMID:27416083

  18. 40 CFR 180.519 - Bromide ion and residual bromine; tolerances for residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Bromide ion and residual bromine... Tolerances § 180.519 Bromide ion and residual bromine; tolerances for residues. (a) General. The food additives, bromide ion and residual bromine, may be present in water, potable in accordance with...

  19. 40 CFR 180.519 - Bromide ion and residual bromine; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Bromide ion and residual bromine... Tolerances § 180.519 Bromide ion and residual bromine; tolerances for residues. (a) General. The food additives, bromide ion and residual bromine, may be present in water, potable in accordance with...

  20. 40 CFR 180.519 - Bromide ion and residual bromine; tolerances for residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Bromide ion and residual bromine... Tolerances § 180.519 Bromide ion and residual bromine; tolerances for residues. (a) General. The food additives, bromide ion and residual bromine, may be present in water, potable in accordance with...

  1. 40 CFR 180.519 - Bromide ion and residual bromine; tolerances for residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Bromide ion and residual bromine... Tolerances § 180.519 Bromide ion and residual bromine; tolerances for residues. (a) General. The food additives, bromide ion and residual bromine, may be present in water, potable in accordance with...

  2. Insights into the mechanism of drug resistance. X-ray structure analysis of multi-drug resistant HIV-1 protease ritonavir complex

    SciTech Connect

    Liu, Zhigang; Yedidi, Ravikiran S.; Wang, Yong; Dewdney, Tamaria G.; Reiter, Samuel J.; Brunzelle, Joseph S.; Kovari, Iulia A.; Kovari, Ladislau C.

    2013-01-08

    Ritonavir (RTV) is a first generation HIV-1 protease inhibitor with rapidly emerging drug resistance. Mutations at residues 46, 54, 82 and 84 render the HIV-1 protease drug resistant against RTV. We report the crystal structure of multi-drug resistant (MDR) 769 HIV-1 protease (carrying resistant mutations at residues 10, 36, 46, 54, 62, 63, 71, 82, 84 and 90) complexed with RTV and the in vitro enzymatic IC50 of RTV against MDR HIV-1 protease. The structural and functional studies demonstrate significant drug resistance of MDR HIV-1 protease against RTV, arising from reduced hydrogen bonds and Van der Waals interactions between RTV and MDR HIV-1 protease.

  3. RESIDUAL STRESSES IN 3013 CONTAINERS

    SciTech Connect

    Mickalonis, J.; Dunn, K.

    2009-11-10

    The DOE Complex is packaging plutonium-bearing materials for storage and eventual disposition or disposal. The materials are handled according to the DOE-STD-3013 which outlines general requirements for stabilization, packaging and long-term storage. The storage vessels for the plutonium-bearing materials are termed 3013 containers. Stress corrosion cracking has been identified as a potential container degradation mode and this work determined that the residual stresses in the containers are sufficient to support such cracking. Sections of the 3013 outer, inner, and convenience containers, in both the as-fabricated condition and the closure welded condition, were evaluated per ASTM standard G-36. The standard requires exposure to a boiling magnesium chloride solution, which is an aggressive testing solution. Tests in a less aggressive 40% calcium chloride solution were also conducted. These tests were used to reveal the relative stress corrosion cracking susceptibility of the as fabricated 3013 containers. Significant cracking was observed in all containers in areas near welds and transitions in the container diameter. Stress corrosion cracks developed in both the lid and the body of gas tungsten arc welded and laser closure welded containers. The development of stress corrosion cracks in the as-fabricated and in the closure welded container samples demonstrates that the residual stresses in the 3013 containers are sufficient to support stress corrosion cracking if the environmental conditions inside the containers do not preclude the cracking process.

  4. South Polar Residual Ice Cap

    NASA Technical Reports Server (NTRS)

    1990-01-01

    This mosaic is composed of 18 Viking Orbiter images (6 each in red, green, and violet filters), acquired on September 28, 1977, during revolution 407 of Viking Orbiter 2. The south pole is located just off the lower left edge of the polar cap, and the 0 degree longitude meridian extends toward the top of the mosaic. The large crater near the right edge (named 'South') is about 100 km in diameter. These images were acquired during southern summer on Mars (Ls = 341 degrees); the sub-solar declination was 8 degrees S., and the south polar cap was nearing its final stage of retreat just prior to vernal equinox. The south residual cap is approximately 400 km across, and the exposed surface is thought to consist dominantly of carbon-dioxide frost. This is in contrast to the water-ice surface of the north polar residual cap. It is likely that water ice is present in layers that underlie the south polar cap and that comprise the surrounding layered terrains. Near the top of this image, irregular pits with sharp-rimmed cliffs appear 'etched', presumably by wind. A series of rugged mountains (extending toward the upper right corner of the image) are of unknown origin.

  5. 75 FR 50771 - Draft Revised Guidance for Industry on Residual Solvents in New Veterinary Medicinal Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-17

    ... Federal Register of May 22, 2001 (66 FR 28182) (the 2001 final guidance), has been developed for... residual solvents in new animal drugs (referred to as pharmaceuticals or veterinary medicinal products in this guidance) for the safety of the target animal as well as for the safety of human consumers...

  6. Residual solvent testing: a review of gas-chromatographic and alternative techniques.

    PubMed

    B'Hymer, Clayton

    2003-03-01

    The purpose of this brief review is to describe and discuss some of the current analytic procedures including gas-chromatographic and alternative techniques for residual solvent testing. Residual solvents, or organic volatile impurities, are a potential toxic risk for pharmaceutic products and have been a concern of manufacturers for many years. Residual solvents have had official limits in the United States as set in USP XXV and by the FDA in 1997 and have been monitored by most pharmaceutical manufacturers extensively for more than two decades in both bulk and finished products. The chief method of analysis for residual solvents is gas chromatography, which is generally considered the preferred methodology. Sample introduction techniques include both static and dynamic headspace analysis, solid-phase microextraction, and direct injection of solution containing bulk drug substance or drug product into the gas chromatograph. Also, some alternative methodologies for residual solvent testing are discussed in this review. In conclusion, gas chromatograph-based procedures will continue to dominate residual solvent testing because of its specificity for identification of the solvent, but the use of alternative sample introduction techniques into a gas chromatograph will continue to expand in the near future.

  7. A Research Agenda for Malaria Eradication: Drugs

    PubMed Central

    2011-01-01

    Antimalarial drugs will be essential tools at all stages of malaria elimination along the path towards eradication, including the early control or “attack” phase to drive down transmission and the later stages of maintaining interruption of transmission, preventing reintroduction of malaria, and eliminating the last residual foci of infection. Drugs will continue to be used to treat acute malaria illness and prevent complications in vulnerable groups, but better drugs are needed for elimination-specific indications such as mass treatment, curing asymptomatic infections, curing relapsing liver stages, and preventing transmission. The ideal malaria eradication drug is a coformulated drug combination suitable for mass administration that can be administered in a single encounter at infrequent intervals and that results in radical cure of all life cycle stages of all five malaria species infecting humans. Short of this optimal goal, highly desirable drugs might have limitations such as targeting only one or two parasite species, the priorities being Plasmodium falciparum and Plasmodium vivax. The malaria research agenda for eradication should include research aimed at developing such drugs and research to develop situation-specific strategies for using both current and future drugs to interrupt malaria transmission. PMID:21311580

  8. Clinically significant drug interactions.

    PubMed

    Ament, P W; Bertolino, J G; Liszewski, J L

    2000-03-15

    A large number of drugs are introduced every year, and new interactions between medications are increasingly reported. Consequently, it is no longer practical for physicians to rely on memory alone to avoid potential drug interactions. Multiple drug regimens carry the risk of adverse interactions. Precipitant drugs modify the object drug's absorption, distribution, metabolism, excretion or actual clinical effect. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Many other drugs, act as precipitants or objects, and a number of drugs act as both. Regularly updated manuals of drug interactions and CD-ROM-formatted programs are useful office references. PMID:10750880

  9. Personality, Drug Preference, Drug Use, and Drug Availability

    ERIC Educational Resources Information Center

    Feldman, Marc; Boyer, Bret; Kumar, V. K.; Prout, Maurice

    2011-01-01

    This study examined the relationship between drug preference, drug use, drug availability, and personality among individuals (n = 100) in treatment for substance abuse in an effort to replicate the results of an earlier study (Feldman, Kumar, Angelini, Pekala, & Porter, 2007) designed to test prediction derived from Eysenck's (1957, 1967)…

  10. Human Food Safety Implications of Variation in Food Animal Drug Metabolism

    PubMed Central

    Lin, Zhoumeng; Vahl, Christopher I.; Riviere, Jim E.

    2016-01-01

    Violative drug residues in animal-derived foods are a global food safety concern. The use of a fixed main metabolite to parent drug (M/D) ratio determined in healthy animals to establish drug tolerances and withdrawal times in diseased animals results in frequent residue violations in food-producing animals. We created a general physiologically based pharmacokinetic model for representative drugs (ceftiofur, enrofloxacin, flunixin, and sulfamethazine) in cattle and swine based on extensive published literature. Simulation results showed that the M/D ratio was not a fixed value, but a time-dependent range. Disease changed M/D ratios substantially and extended withdrawal times; these effects exhibited drug- and species-specificity. These results challenge the interpretation of violative residues based on the use of the M/D ratio to establish tolerances for metabolized drugs. PMID:27302389

  11. Keys to a drug-free workplace

    NASA Astrophysics Data System (ADS)

    Fortuna, Joseph J.; Fortuna, Patricia B.

    1997-01-01

    What does it take to establish a drug free work place. Are technologies available other than urine testing for pre- employment screening and monitoring of employees. Various methods are now available to screen for illicit drug residues on items handled by individuals. The residues can be acquired from the surfaces of items such as telephones, door knobs, steering wheels, lockers, clothing, identification cards, etc. Test kits are also available for urine testing at NIDA threshold levels. Analysis of hair, saliva, and sweat is now possible. How good ar these methods and kits. What value are they to the public. What are the legal concerns facing employers. What do the screening test show. These questions and others are addressed in this paper. The authors review for the reader how drug abuse by US workers costs businesses. The paper then addresses the various aspects of the DOT regulations to determine why urine analysis (UA) is insufficient to eliminate drug abuse. The authors present applications of screening technologies in addition to UA. Finally, the authors provide a conclusion of findings and recommendations for businesses that truly want or need drug free work places.

  12. Patents for ELISA tests to detect antibiotic residues in foods of animal origin.

    PubMed

    Reig, Milagro; Toldrá, Fidel

    2011-05-01

    The use of antibiotics in the European Union was banned since the 1(st) of January 2006. At present, and even though such ban, residues of drugs used in animal therapy or, illegally, as growth promoters might be found in food. Such residues may cause adverse health effects on consumers like allergic reactions in sensitive individuals develop transmissible antimicrobial resistance in food microflora, and have technological implications in the manufacture of fermented products. This is the reason why to check food for the presence of antibiotics residues is still necessary. ELISA test constitutes an attractive screening technique due to its simplicity, large number of samples per kit and possibility of automation. The aim of this manuscript is to provide a review of the numerous patents and applications for the analysis of antibiotic residues in foods. PMID:21428870

  13. Patents for ELISA tests to detect antibiotic residues in foods of animal origin.

    PubMed

    Reig, Milagro; Toldrá, Fidel

    2011-05-01

    The use of antibiotics in the European Union was banned since the 1(st) of January 2006. At present, and even though such ban, residues of drugs used in animal therapy or, illegally, as growth promoters might be found in food. Such residues may cause adverse health effects on consumers like allergic reactions in sensitive individuals develop transmissible antimicrobial resistance in food microflora, and have technological implications in the manufacture of fermented products. This is the reason why to check food for the presence of antibiotics residues is still necessary. ELISA test constitutes an attractive screening technique due to its simplicity, large number of samples per kit and possibility of automation. The aim of this manuscript is to provide a review of the numerous patents and applications for the analysis of antibiotic residues in foods.

  14. Minimal residual disease in cancer therapy--Small things make all the difference.

    PubMed

    Blatter, Sohvi; Rottenberg, Sven

    2015-01-01

    Minimal residual disease (MRD) is a major hurdle in the eradication of malignant tumors. Despite the high sensitivity of various cancers to treatment, some residual cancer cells persist and lead to tumor recurrence and treatment failure. Obvious reasons for residual disease include mechanisms of secondary therapy resistance, such as the presence of mutant cells that are insensitive to the drugs, or the presence of cells that become drug resistant due to activation of survival pathways. In addition to such unambiguous resistance modalities, several patients with relapsing tumors do not show refractory disease and respond again when the initial therapy is repeated. These cases cannot be explained by the selection of mutant tumor cells, and the precise mechanisms underlying this clinical drug resistance are ill-defined. In the current review, we put special emphasis on cell-intrinsic and -extrinsic mechanisms that may explain mechanisms of MRD that are independent of secondary therapy resistance. In particular, we show that studying genetically engineered mouse models (GEMMs), which highly resemble the disease in humans, provides a complementary approach to understand MRD. In these animal models, specific mechanisms of secondary resistance can be excluded by targeted genetic modifications. This allows a clear distinction between the selection of cells with stable secondary resistance and mechanisms that result in the survival of residual cells but do not provoke secondary drug resistance. Mechanisms that may explain the latter feature include special biochemical defense properties of cancer stem cells, metabolic peculiarities such as the dependence on autophagy, drug-tolerant persisting cells, intratumoral heterogeneity, secreted factors from the microenvironment, tumor vascularization patterns and immunosurveillance-related factors. We propose in the current review that a common feature of these various mechanisms is cancer cell dormancy. Therefore, dormant cancer

  15. Organochlorine residues in finfish from Maryland waters 1976-1980

    SciTech Connect

    Eisenberg, M.; Topping, J.J.

    1985-12-01

    Organochlorine pesticide and herbicide levels were monitored in samples of a variety of edible finfish harvested from the Maryland section of the Chesapeake Bay and its tributaries over a five-year period (1976-80). Qualitative and quantitative information was obtained for the various polychlorinated biphenyls (PCB's), heptachlor, alpha-BHC, chlordane, DDD, DDE, DDT, dieldrin, endrin, heptachlorepoxide, lindane, mirex, methoxychlor, aldrin, toxaphene, hexachlorobenzene, kepone and dacthal. In addition to analyses of the flesh of the animals, organochlorine residue levels were determined in roe or gonad tissue of several samples. Striped bass, white perch and yellow perch samples showed significantly higher concentrations of certain of these substances in roe or gonad tissue, especially PCB's, chlordane, DDD and dieldrin. Significantly higher levels of six organochlorine residues were found in the gonad tissue of striped bass; however, similar studies on gonad tissue of American Shad, harvested from the same region, show no such enhancement. Rather, the reverse is true; levels of certain organochlorine residues are higher in flesh tissue. All mean values, and virtually all individual values of organochlorine concentrations in the edible portion of the fish were within the U.S. Food and Drug Administration guideline, where such guidelines have been established.

  16. 99 Films on Drugs.

    ERIC Educational Resources Information Center

    Weber, David O., Ed.

    This catalog describes and evaluates 16-millimeter films about various aspects of drug use. Among the subjects covered by the 99 films are the composition and effects of different drugs, reasons why people use drugs, life in the drug culture, the problem of law enforcement, and various means of dealing with drug users. Each film is synopsized. Two…

  17. Simultaneous screening analysis of 3-methyl-quinoxaline-2-carboxylic acid and quinoxaline-2-carboxylic acid residues in edible animal tissues by a competitive indirect immunoassay

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Immunoassays contribute greatly to veterinary drug residue analysis and food safety, but there are no reported immunoassays on simultaneously detecting MQCA and QCA, the marker residues for carbadox and olaquindox. It is extremely difficult to produce broad-specificity antibodies that bind both res...

  18. New Method for the Analysis of Flukicide and Other Anthelmintic Residues in Bovine Milk and Liver using LC-MS/MS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) multi-residue method for the simultaneous quantification and identification of 38 residues of the most widely used anthelmintic veterinary drugs (including benzimidazoles, macrocyclic lactones, and flukicides) in milk and liver has been d...

  19. Fate of ivermectin residues in ewes' milk and derived products.

    PubMed

    Cerkvenik, Vesna; Perko, Bogdan; Rogelj, Irena; Doganoc, Darinka Z; Skubic, Valentin; Beek, Wim M J; Keukens, Henk J

    2004-02-01

    The fate of ivermectin (IVM) residues was studied throughout the processing of daily bulk milk from 30 ewes (taken up to 33 d following subcutaneous administration of 0.2 mg IVM/kg b.w.) in the following milk products: yoghurt made from raw and pasteurized milk; cheese after pressing; 30- and 60-day ripened cheese; and whey, secondary whey and whey proteins obtained after cheese-making (albumin cheese). The concentration of the H2B1a component of IVM was analysed in these dairy products using an HPLC method with fluorescence detection. The mean recovery of the method was, depending on the matrix, between 87 and 100%. Limits of detection in the order of only 0.1 microg H2B1a/kg of product were achieved. Maximum concentrations of IVM were detected mostly at 2 d after drug administration to the ewes. The highest concentration of IVM was found on day 2 in 60-day ripened cheese (96 microg H2B1a/kg cheese). Secondary whey was the matrix with the lowest concentration of IVM (<0.6 microg H2B1a/ kg). Residue levels fell below the limits of detection between day 5 (for secondary whey) and day 25 (for all cheese samples). In the matrices investigated, linear correlations between daily concentrations of IVM, milk fat and solid content were evident. During yoghurt production, fermentation and thermal stability of IVM was observed. During cheese production, approximately 35% of the IVM, present in the raw (bulk) milk samples, was lost. From the results it was concluded that the processing of ewes' milk did not eliminate the drug residues under investigation. The consequences of IVM in the human diet were discussed. Milk from treated animals should be excluded from production of fat products like cheese for longer after treatment with IVM than for lower fat products.

  20. Studies Of Residual Flexibility And Vibration Testing

    NASA Technical Reports Server (NTRS)

    Admire, John R.; Tinker, Michael L.; Bookout, Paul S.; Ivey, Edward W.

    1995-01-01

    Collection of reports presents theoretical and experimental studies in which concept of residual flexibility applied to modal vibration testing and verification of mathematical models of vibrations of flexible structure constrained by another structure. "Residual flexibility" denotes that part of interface flexibility due to mode shapes out of frequency range of test. Studies directed toward assessing residual-flexibility approach as substitute for fixed-base vibrational testing of payloads installed in spacecraft.

  1. Residual stresses in polymer matrix composite laminates

    NASA Technical Reports Server (NTRS)

    Hahn, H. T.

    1976-01-01

    Residual stresses in composites are induced during fabrication and by environmental exposure. The theory formulated can describe the shrinkage commonly observed after a thermal expansion test. Comparison between the analysis and experimental data for laminates of various material systems indicates that the residual stress-free temperature can be lower than the curing temperature, depending on the curing process. Effects of residual stresses on ply failure including the acoustic emission characteristics are discussed.

  2. Optical systolic array processor using residue arithmetic

    NASA Technical Reports Server (NTRS)

    Jackson, J.; Casasent, D.

    1983-01-01

    The use of residue arithmetic to increase the accuracy and reduce the dynamic range requirements of optical matrix-vector processors is evaluated. It is determined that matrix-vector operations and iterative algorithms can be performed totally in residue notation. A new parallel residue quantizer circuit is developed which significantly improves the performance of the systolic array feedback processor. Results are presented of a computer simulation of this system used to solve a set of three simultaneous equations.

  3. Residues of profenofos in spring onion.

    PubMed

    Talebi, K; Ghassami, M R

    2004-01-01

    Profenofos is one of the commonly used insecticides in the control of Trips tabaci on spring onion in Iran. Residues of profenofos in spring onion were determined in two different fields under the same conditions. In the first field, onion plants were sprayed with profenofos (40EC) at the rate of 1000 g/ha. Spraying was repeated 2 weeks later. In the second field one spraying was preformed at the same rate. Spring onionwere sampled at different time intervals and analyzed for profenofos residues using a GC equipped with NPD detector. In the first field's samples, the residues were 0.097 and 0.025 mg/kg at 2 and 6 days after spraying, respectively. The residues declined to 0.002 mg/kg on the day twelve. Two days after the second spraying the residues was 0.27 mg/kg, which reduced to 0.032 on the day sixth. However the residues were not detectable 32 days after the second spraying. In the second field, residue levels were 0.193 and 0.043 mg/kg at 2 and 6 days after spraying. Residues, which found after 32 days, were less than 0.001 mg/kg. The rate of residue decay in the first field was higher than the second field. PMID:15756871

  4. Methods of separating particulate residue streams

    DOEpatents

    Hoskinson, Reed L.; Kenney, Kevin L.; Wright, Christopher T.; Hess, J. Richard

    2011-04-05

    A particulate residue separator and a method for separating a particulate residue stream may include an air plenum borne by a harvesting device, and have a first, intake end and a second, exhaust end; first and second particulate residue air streams that are formed by the harvesting device and that travel, at least in part, along the air plenum and in a direction of the second, exhaust end; and a baffle assembly that is located in partially occluding relation relative to the air plenum and that substantially separates the first and second particulate residue air streams.

  5. 21 CFR 500.26 - Timed-release dosage form drugs.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... effective rate and that these release characteristics will be maintained until the expiration date of the... that, with respect to possible residues of the drug, food derived from treated animals is safe...

  6. A CD138-independent strategy to detect minimal residual disease and circulating tumour cells in multiple myeloma.

    PubMed

    Muz, Barbara; de la Puente, Pilar; Azab, Feda; Luderer, Micah John; King, Justin; Vij, Ravi; Azab, Abdel Kareem

    2016-04-01

    CD138 (also termed SDC1) has been the gold-standard surface marker to detect multiple myeloma (MM) cells for decades; however, drug-resistant residual and circulating MM cells were shown to have lower expression of this marker. In this study, we have shown that residual MM cells following bortezomib treatment are hypoxic. This combination of drug exposure and hypoxia down-regulates their CD138 expression, thereby making this marker unsuitable for detecting residual or other hypoxic MM cells, such as circulating tumour cells, in MM. Hence, we developed an alternative biomarker set which detects myeloma cells independent of their hypoxic and CD138 expression status in vitro, in vivo and in primary MM patients. The new markers were able to identify a clonal CD138-negative population as minimal residual disease in the bone marrow and peripheral blood of MM patients. Further investigation to characterize the role of this population as a prognostic marker in MM is warranted.

  7. [Ilicit drugs frequently used by drug addicts].

    PubMed

    Cirriez, J P

    2015-03-01

    Drugs stimulate the brain causing mental and physical effects. The effects of drugs can be stimulating, narcotic or mind-altering. This article briefly discusses some commonly used illicit drugs, namely heroin, cocaine, cannabis, ecstasy, amphetamines, LSD, psilocybin mushrooms and poppers. PMID:26571792

  8. Attitudes towards drug legalization among drug users.

    PubMed

    Trevino, Roberto A; Richard, Alan J

    2002-01-01

    Research shows that support for legalization of drugs varies significantly among different sociodemographic and political groups. Yet there is little research examining the degree of support for legalization of drugs among drug users. This paper examines how frequency and type of drug use affect the support for legalization of drugs after adjusting for the effects of political affiliation and sociodemographic characteristics. A sample of 188 drug users and non-drug users were asked whether they would support the legalization of marijuana, cocaine, and heroin. Respondents reported their use of marijuana, crack, cocaine, heroin, speedball, and/or methamphetamines during the previous 30 days. Support for legalization of drugs was analyzed by estimating three separate logistic regressions. The results showed that the support for the legalization of drugs depended on the definition of "drug user" and the type of drug. In general, however, the results showed that marijuana users were more likely to support legalizing marijuana, but they were less likely to support the legalization of cocaine and heroin. On the other hand, users of crack, cocaine, heroin, speedball, and/or methamphetamines were more likely to support legalizing all drugs including cocaine and heroin.

  9. Drug Use by Students of Drug Abuse

    ERIC Educational Resources Information Center

    Linder, Ronald; And Others

    1973-01-01

    The purpose of this study was to determine the significance of differences in the use of certain psychoactive drugs among students who enrolled for an elective drug abuse course and students not enrolled, or who have not previously taken a drug abuse course. (Author)

  10. Discontinued drugs in 2008: cardiovascular drugs.

    PubMed

    Zhang, Xu-Song; Xiang, Bing-Ren

    2009-07-01

    This perspective is part of an annual series of papers discussing drugs dropped from clinical development in the previous year. Specifically, this paper focuses on the 16 cardiovascular drugs discontinued in 2008. Information for this perspective was derived from a search of the Pharmaprojects database for drugs discontinued after reaching Phase I-III clinical trials. PMID:19548849

  11. Access to Investigational Drugs

    MedlinePlus

    ... drug if the supply is limited and the demand is high. Are all investigational drugs available through ... be limited in part by drug supply, patient demand, or other factors. What is NCI’s role in ...

  12. Drug Development Process

    MedlinePlus

    ... Approvals The Drug Development Process The Drug Development Process Share Tweet Linkedin Pin it More sharing options ... public. More Information More in The Drug Development Process Step 1: Discovery and Development Step 2: Preclinical ...

  13. Drugs Approved for Leukemia

    MedlinePlus

    ... Ask about Your Treatment Research Drugs Approved for Leukemia This page lists cancer drugs approved by the ... not listed here. Drugs Approved for Acute Lymphoblastic Leukemia (ALL) Abitrexate (Methotrexate) Arranon (Nelarabine) Asparaginase Erwinia chrysanthemi ...

  14. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user.

  15. Drug Retention Times

    SciTech Connect

    Center for Human Reliability Studies

    2007-05-01

    The purpose of this monograph is to provide information on drug retention times in the human body. The information provided is based on plausible illegal drug use activities that might be engaged in by a recreational drug user

  16. Drug-induced hepatitis

    MedlinePlus

    Toxic hepatitis ... to get liver damage. Some drugs can cause hepatitis with small doses, even if the liver breakdown ... liver. Many different drugs can cause drug-induced hepatitis. Painkillers and fever reducers that contain acetaminophen are ...

  17. Partitioning Residue-derived and Residue-induced Emissions of N2O Using 15N-labelled Crop Residues

    NASA Astrophysics Data System (ADS)

    Farrell, R. E.; Carverhill, J.; Lemke, R.; Knight, J. D.

    2014-12-01

    Estimates of N2O emissions in Canada indicate that 17% of all agriculture-based emissions are associated with the decomposition of crop residues. However, research specific to the western Canadian prairies (including Saskatchewan) has shown that the N2O emission factor for N sources in this region typically ranges between 0.2 and 0.6%, which is well below the current IPCC default emission factor of 1.0%. Thus, it stands to reason that emissions from crop residues should also be lower than those calculated using the current IPCC emission factor. Current data indicates that residue decomposition, N mineralization and N2O production are affected by a number of factors such as C:N ratio and chemical composition of the residue, soil type, and soil water content; thus, a bench-scale incubation study was conducted to examine the effects of soil type and water content on N2O emissions associated with the decomposition of different crop residues. The study was carried out using soils from the Black, Dark Brown, Brown, and Gray soil zones and was conducted at both 50% and 70% water-filled pore space (WFPS); the soils were amended with 15N-labeled residues of wheat, pea, canola, and flax, or with an equivalent amount of 15N-labeled urea; 15N2O production was monitored using a Picarro G5101-i isotopic N2O analyzer. Crop residue additions to the soils resulted in both direct and indirect emissions of N2O, with residue derived emissions (RDE; measured as 15N2O) generally exceeding residue-induced emissions (RIE) at 50% WFPS—with RDEs ranging from 42% to 88% (mean = 58%) of the total N2O. Conversely, at 70% WFPS, RDEs were generally lower than RIEs—ranging from 21% to 83% (mean = 48%). Whereas both water content and soil type had an impact on N2O production, there was a clear and consistent trend in the emission factors for the residues; i.e., emissions were always greatest for the canola residue and lowest for the wheat residue and urea fertilizer; and intermediate for pea

  18. ORAL ADVERSE DRUG REACTIONS TO CARDIOVASCULAR DRUGS.

    PubMed

    Torpet, Lis Andersen; Kragelund, Camilla; Reibel, Jesper; Nauntofte, Birgitte

    2004-01-01

    A great many cardiovascular drugs (CVDs) have the potential to induce adverse reactions in the mouth. The prevalence of such reactions is not known, however, since many are asymptomatic and therefore are believed to go unreported. As more drugs are marketed and the population includes an increasing number of elderly, the number of drug prescriptions is also expected to increase. Accordingly, it can be predicted that the occurrence of adverse drug reactions (ADRs), including the oral ones (ODRs), will continue to increase. ODRs affect the oral mucous membrane, saliva production, and taste. The pathogenesis of these reactions, especially the mucosal ones, is largely unknown and appears to involve complex interactions among the drug in question, other medications, the patient's underlying disease, genetics, and life-style factors. Along this line, there is a growing interest in the association between pharmacogenetic polymorphism and ADRs. Research focusing on polymorphism of the cytochrome P450 system (CYPs) has become increasingly important and has highlighted the intra- and inter-individual responses to drug exposure. This system has recently been suggested to be an underlying candidate regarding the pathogenesis of ADRs in the oral mucous membrane. This review focuses on those CVDs reported to induce ODRs. In addition, it will provide data on specific drugs or drug classes, and outline and discuss recent research on possible mechanisms linking ADRs to drug metabolism patterns. Abbreviations used will be as follows: ACEI, ACE inhibitor; ADR, adverse drug reaction; ANA, antinuclear antigen; ARB, angiotensin II receptor blocker; BAB, beta-adrenergic blocker; CCB, calcium-channel blocker; CDR, cutaneous drug reaction; CVD, cardiovascular drug; CYP, cytochrome P450 enzyme; EM, erythema multiforme; FDE, fixed drug eruption; I, inhibitor of CYP isoform activity; HMG-CoA, hydroxymethyl-glutaryl coenzyme A; NAT, N-acetyltransferase; ODR, oral drug reaction; RDM, reactive

  19. [Drug-induced dementia].

    PubMed

    Kojima, Taro; Akishita, Masahiro

    2016-03-01

    Many drugs have been reported to induce not only delirium but also cognitive impairment. Some types of drugs are reported to induce dementia, and prolonged hypotension or hypoglycemia induced by overuse of antihypertensive drugs or oral antidiabetic drugs could result in dementia. Recently, taking multiple drugs with anticholinergic activity are reported to cause cognitive decline and anticholinergic burden should be avoided especially in patients with dementia. Drug-induced dementia can be prevented by avoiding polypharmacy and adhering to the saying 'start low and go slow' . Early diagnosis of drug-induced dementia and withdrawal of the offending drug is essential to improve cognitive function. PMID:27025096

  20. Nanoencapsulation for drug delivery

    PubMed Central

    Kumari, Avnesh; Singla, Rubbel; Guliani, Anika; Yadav, Sudesh Kumar

    2014-01-01

    Nanoencapsulation of drug/small molecules in nanocarriers (NCs) is a very promising approach for development of nanomedicine. Modern drug encapsulation methods allow efficient loading of drug molecules inside the NCs thereby reducing systemic toxicity associated with drugs. Targeting of NCs can enhance the accumulation of nanonencapsulated drug at the diseased site. This article focussed on the synthesis methods, drug loading, drug release mechanism and cellular response of nanoencapsulated drugs on liposomes, micelles, carbon nanotubes, dendrimers, and magnetic NCs. Also the uses of these various NCs have been highlighted in the field of nanotechnology. PMID:26417260

  1. A Benchmark Study on Casting Residual Stress

    SciTech Connect

    Johnson, Eric M.; Watkins, Thomas R; Schmidlin, Joshua E; Dutler, S. A.

    2012-01-01

    Stringent regulatory requirements, such as Tier IV norms, have pushed the cast iron for automotive applications to its limit. The castings need to be designed with closer tolerances by incorporating hitherto unknowns, such as residual stresses arising due to thermal gradients, phase and microstructural changes during solidification phenomenon. Residual stresses were earlier neglected in the casting designs by incorporating large factors of safety. Experimental measurement of residual stress in a casting through neutron or X-ray diffraction, sectioning or hole drilling, magnetic, electric or photoelastic measurements is very difficult and time consuming exercise. A detailed multi-physics model, incorporating thermo-mechanical and phase transformation phenomenon, provides an attractive alternative to assess the residual stresses generated during casting. However, before relying on the simulation methodology, it is important to rigorously validate the prediction capability by comparing it to experimental measurements. In the present work, a benchmark study was undertaken for casting residual stress measurements through neutron diffraction, which was subsequently used to validate the accuracy of simulation prediction. The stress lattice specimen geometry was designed such that subsequent castings would generate adequate residual stresses during solidification and cooling, without any cracks. The residual stresses in the cast specimen were measured using neutron diffraction. Considering the difficulty in accessing the neutron diffraction facility, these measurements can be considered as benchmark for casting simulation validations. Simulations were performed using the identical specimen geometry and casting conditions for predictions of residual stresses. The simulation predictions were found to agree well with the experimentally measured residual stresses. The experimentally validated model can be subsequently used to predict residual stresses in different cast

  2. Gunshot residue preservation in seawater.

    PubMed

    Lindström, Anne-Christine; Hoogewerff, Jurian; Athens, Josie; Obertova, Zuzana; Duncan, Warwick; Waddell, Neil; Kieser, Jules

    2015-08-01

    Little is known about the persistence of gunshot residue (GSR) in soft tissue and bones during decomposition in marine environments. For a better understanding, qualitative and quantitative data were obtained on GSR retention on soft tissue and bony gunshot wounds (GSWs). A quantity of 36 fleshed and 36 defleshed bovine ribs were shot at contact range with 0.22 calibre hollow point ammunition using a Stirling 0.22 calibre long rifle. Bone specimens in triplicate were placed in three environments: submerged, intertidal and in supralittoral zone. Sets of triplicates were recovered on day 3, 10, 24 and 38, and analysed with scanning electron microscopy with energy dispersive X-ray spectrometry (SEM-EDX), and inductive coupled plasma mass spectrometry (ICP-MS). The SEM-EDX recorded GSR-indicative particles surrounding the bullet entrance on all bone types (fleshed and defleshed) in all environments throughout the study. GSR-unique particles were only detected on the supralittoral bones. The ICP-MS analysis showed faster GSR loss on submerged than intertidal and supralittoral defleshed specimens. Fleshed specimens showed a faster GSR loss on intertidal than submerged and supralittoral specimens. In conclusion, the GSR disappeared faster from submerged and intertidal than non-submerged specimens. The difference of detection of GSR between analysed specimens (defleshed versus fleshed) disappeared upon defleshing. This study highlights the potential of finding evidence of GSR in a submerged body and the potential of microscopic and analytical methods for examining suspected GSW in highly decomposed bodies in marine habitats.

  3. Thermal Insulation from Hardwood Residues

    NASA Astrophysics Data System (ADS)

    Sable, I.; Grinfelds, U.; Vikele, L.; Rozenberga, L.; Zeps, M.; Luguza, S.

    2015-11-01

    Adequate heat is one of the prerequisites for human wellbeing; therefore, building insulation is required in places where the outside temperature is not suitable for living. The climate change, with its rising temperatures and longer dry periods, promotes enlargement of the regions with conditions more convenient for hardwood species than for softwood species. Birch (Betula pendula) is the most common hardwood species in Latvia. The aim of this work was to obtain birch fibres from wood residues of plywood production and to form low-density thermal insulation boards. Board formation and production was done in the presence of water; natural binder, fire retardant and fungicide were added in different concentrations. Board properties such as density, transportability or resistance to particulate loss, thermal conductivity and reaction to fire were investigated. This study included thermal insulation boards with the density of 102-120 kg/m3; a strong correlation between density and the binder amount was found. Transportability also improved with the addition of a binder, and 0.1-0.5% of the binder was the most appropriate amount for this purpose. The measured thermal conductivity was in the range of 0.040-0.043 W/(m·K). Fire resistance increased with adding the fire retardant. We concluded that birch fibres are applicable for thermal insulation board production, and it is possible to diversify board properties, changing the amount of different additives.

  4. Catalyst deactivation in residue hydrocracking

    SciTech Connect

    Oballa, M.C.; Wong, C.; Krzywicki, A.

    1994-12-31

    The existence of a computer-controlled bench scale hydrocracking units at the authors site has made cheaper the non-stop running of experiments for long periods of time. It was, therefore possible to show, at minimal costs, when three hydrocracking catalysts in service reach their maximum lifetime. Different parameters which are helpful for catalyst life and activity predictions were calculated, e.g., relative catalyst age and the effectiveness factor. Experimental results compared well with model, giving them the minimum and maximum catalyst lifetime, as well as the deactivation profile with regard to sulfur and metals removal. Reaction rate constants for demetallization and desulfurization were also determined. Six commercial catalysts were evaluated at short term runs and the three most active were used for long term runs. Out of three catalysts tested for deactivation at long term runs, it was possible to choose one whose useful life was higher than the others. All runs were carried out in a Robinson-Mahoney continuous flow stirred tank reactor, using 50/50 volumetric mixture of Cold Lake/Lloydminster atmospheric residue and NiMo/Al{sub 2}O{sub 3} catalyst.

  5. Characterization Report on Sand, Slag, and Crucible Residues and on Fluoride Residues

    SciTech Connect

    Murray, A.M.

    1999-02-10

    This paper reports on the chemical characterization of the sand, slag, and crucible (SS and C) residues and the fluoride residues that may be shipped from the Rocky Flats Environmental Technology Site (RFETS) to Savannah River Site (SRS).

  6. Use of Combined Uncertainty of Pesticide Residue Results for Testing Compliance with Maximum Residue Limits (MRLs).

    PubMed

    Farkas, Zsuzsa; Slate, Andrew; Whitaker, Thomas B; Suszter, Gabriella; Ambrus, Árpád

    2015-05-13

    The uncertainty of pesticide residue levels in crops due to sampling, estimated for 106 individual crops and 24 crop groups from residue data obtained from supervised trials, was adjusted with a factor of 1.3 to accommodate the larger variability of residues under normal field conditions. Further adjustment may be necessary in the case of mixed lots. The combined uncertainty of residue data including the contribution of sampling is used for calculation of an action limit, which should not be exceeded when compliance with maximum residue limits is certified as part of premarketing self-control programs. On the contrary, for testing compliance of marketed commodities the residues measured in composite samples should be greater than or equal to the decision limit calculated only from the combined uncertainty of the laboratory phase of the residue determination. The options of minimizing the combined uncertainty of measured residues are discussed. The principles described are also applicable to other chemical contaminants. PMID:25658668

  7. Nuclear Receptors in Drug Metabolism, Drug Response and Drug Interactions

    PubMed Central

    Prakash, Chandra; Zuniga, Baltazar; Song, Chung Seog; Jiang, Shoulei; Cropper, Jodie; Park, Sulgi; Chatterjee, Bandana

    2016-01-01

    Orally delivered small-molecule therapeutics are metabolized in the liver and intestine by phase I and phase II drug-metabolizing enzymes (DMEs), and transport proteins coordinate drug influx (phase 0) and drug/drug-metabolite efflux (phase III). Genes involved in drug metabolism and disposition are induced by xenobiotic-activated nuclear receptors (NRs), i.e. PXR (pregnane X receptor) and CAR (constitutive androstane receptor), and by the 1α, 25-dihydroxy vitamin D3-activated vitamin D receptor (VDR), due to transactivation of xenobiotic-response elements (XREs) present in phase 0-III genes. Additional NRs, like HNF4-α, FXR, LXR-α play important roles in drug metabolism in certain settings, such as in relation to cholesterol and bile acid metabolism. The phase I enzymes CYP3A4/A5, CYP2D6, CYP2B6, CYP2C9, CYP2C19, CYP1A2, CYP2C8, CYP2A6, CYP2J2, and CYP2E1 metabolize >90% of all prescription drugs, and phase II conjugation of hydrophilic functional groups (with/without phase I modification) facilitates drug clearance. The conjugation step is mediated by broad-specificity transferases like UGTs, SULTs, GSTs. This review delves into our current understanding of PXR/CAR/VDR-mediated regulation of DME and transporter expression, as well as effects of single nucleotide polymorphism (SNP) and epigenome (specified by promoter methylation, histone modification, microRNAs, long non coding RNAs) on the expression of PXR/CAR/VDR and phase 0-III mediators, and their impacts on variable drug response. Therapeutic agents that target epigenetic regulation and the molecular basis and consequences (overdosing, underdosing, or beneficial outcome) of drug-drug/drug-food/drug-herb interactions are also discussed. Precision medicine requires understanding of a drug’s impact on DME and transporter activity and their NR-regulated expression in order to achieve optimal drug efficacy without adverse drug reactions. In future drug screening, new tools such as humanized mouse models and

  8. Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-01

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

  9. 48 CFR 1450.104 - Residual powers.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Residual powers. 1450.104 Section 1450.104 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.104 Residual powers....

  10. BOOSTER CHLORINATION FOR MANAGING DISINFECTANT RESIDUALS

    EPA Science Inventory

    Booster chlorination is an approach to residual maintenance in which chlorine is applied at strategic locations within the distribution system. Situations in which booster chlorination may be most effective for maintaining a residual are explained informally in the context of a ...

  11. Crop Residues: The Rest of the Story

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recent scientific publication stated that to remove CO2 from the atmosphere, the most permanent and rapid solution would be to sink crop residues to the ocean floor where they would be buried in deep ocean sediments. However, mitigating rising atmospheric CO2 concentrations by removing crop residu...

  12. 40 CFR 240.208 - Residue.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Residue. 240.208 Section 240.208 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended Procedures § 240.208 Residue....

  13. 40 CFR 240.208 - Residue.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Residue. 240.208 Section 240.208 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended Procedures § 240.208 Residue....

  14. 40 CFR 240.208 - Residue.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Residue. 240.208 Section 240.208 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended Procedures § 240.208 Residue....

  15. 40 CFR 240.208 - Residue.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Residue. 240.208 Section 240.208 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES GUIDELINES FOR THE THERMAL PROCESSING OF SOLID WASTES Requirements and Recommended Procedures § 240.208 Residue....

  16. Residuals Management and Water Pollution Control Planning.

    ERIC Educational Resources Information Center

    Environmental Protection Agency, Washington, DC. Office of Public Affairs.

    This pamphlet addresses the problems associated with residuals and water quality especially as it relates to the National Water Pollution Control Program. The types of residuals and appropriate management systems are discussed. Additionally, one section is devoted to the role of citizen participation in developing management programs. (CS)

  17. Soil water evaporation and crop residues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crop residues have value when left in the field and also when removed from the field and sold as a commodity. Reducing soil water evaporation (E) is one of the benefits of leaving crop residues in place. E was measured beneath a corn canopy at the soil suface with nearly full coverage by corn stover...

  18. Measurment Of Residual Stress In Ferromagnetic Materials

    NASA Technical Reports Server (NTRS)

    Namkung, Min; Yost, William T.; Kushnick, Peter W.; Grainger, John L.

    1992-01-01

    Magnetoacoustic (MAC) and magnetoacoustic emission (MAE) techniques combined to provide complete characterization of residual stresses in ferromagnetic structural materials. Combination of MAC and MAE techniques makes it possible to characterize residual tension and compression without being limited by surface conditions and unavailability of calibration standards. Significant in field of characterization of materials as well as detection of fatigue failure.

  19. THE IMMIGRANT POOR AND THE RESIDUAL POOR.

    ERIC Educational Resources Information Center

    SEGALMAN, RALPH

    AN ANALYSIS OF THE LIVES OF THE POOR IN AMERICA WILL SHOW DIFFERENCES BETWEEN THE IMMIGRANT (AND REFUGEE) POOR AND THE RESIDUAL POOR (NEGROES, PUERTO RICANS, LATIN AMERICANS, INDIANS, AND OTHERS). THE IMMIGRANT POOR WERE ACCULTURATED AND ABSORBED INTO THE MAINSTREAM OF AMERICAN LIFE WITHIN THREE GENERATIONS, WHEREAS THE RESIDUAL POOR HAVE BEEN…

  20. 9 CFR 311.39 - Biological residues.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Biological residues. 311.39 Section 311.39 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... Biological residues. Carcasses, organs, or other parts of carcasses of livestock shall be condemned if it...

  1. Unicystic ameloblastoma arising from a residual cyst

    PubMed Central

    Mahajan, Amit D; Manjunatha, Bhari Sharanesha; Khurana, Neha M; Shah, Navin

    2014-01-01

    Intraoral swellings involving alveolar ridges in edentulous patients are clinically diagnosed as residual cysts, traumatic bone cysts, Stafne's jaw bone cavity, ameloblastoma and metastatic tumours of the jaw. This case report describes a residual cyst in a 68-year-old edentulous male patient which was enucleated and histopathologically confirmed as a unicystic ameloblastoma. PMID:25199192

  2. 48 CFR 1450.104 - Residual powers.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Residual powers. 1450.104 Section 1450.104 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.104 Residual powers....

  3. 48 CFR 1450.104 - Residual powers.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Residual powers. 1450.104 Section 1450.104 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.104 Residual powers....

  4. 48 CFR 1450.104 - Residual powers.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Residual powers. 1450.104 Section 1450.104 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.104 Residual powers....

  5. 48 CFR 1450.104 - Residual powers.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Residual powers. 1450.104 Section 1450.104 Federal Acquisition Regulations System DEPARTMENT OF THE INTERIOR CONTRACT MANAGEMENT EXTRAORDINARY CONTRACTUAL ACTIONS AND THE SAFETY ACT Extraordinary Contractual Actions 1450.104 Residual powers....

  6. Tank 12H residuals sample analysis report

    SciTech Connect

    Oji, L. N.; Shine, E. P.; Diprete, D. P.; Coleman, C. J.; Hay, M. S.

    2015-06-11

    The Savannah River National Laboratory (SRNL) was requested by Savannah River Remediation (SRR) to provide sample preparation and analysis of the Tank 12H final characterization samples to determine the residual tank inventory prior to grouting. Eleven Tank 12H floor and mound residual material samples and three cooling coil scrape samples were collected and delivered to SRNL between May and August of 2014.

  7. RECOVERY OF URANIUM VALUES FROM RESIDUES

    DOEpatents

    Schaap, W.B.

    1959-08-18

    A process is described for the recovery of uranium from insoluble oxide residues resistant to repeated leaching with mineral acids. The residue is treated with gaseous hydrogen fluoride, then with hydrogen and again with hydrogen fluoride, preferably at 500 to 700 deg C, prior to the mineral acid leaching.

  8. Residuals and the Residual-Based Statistic for Testing Goodness of Fit of Structural Equation Models

    ERIC Educational Resources Information Center

    Foldnes, Njal; Foss, Tron; Olsson, Ulf Henning

    2012-01-01

    The residuals obtained from fitting a structural equation model are crucial ingredients in obtaining chi-square goodness-of-fit statistics for the model. The authors present a didactic discussion of the residuals, obtaining a geometrical interpretation by recognizing the residuals as the result of oblique projections. This sheds light on the…

  9. [Residues of tetracycline and quinolones in wild fish living around a salmon aquaculture center in Chile].

    PubMed

    Fortt Z, Antonia; Cabello C, Felipe; Buschmann R, Alejandro

    2007-02-01

    The presence of residues of tetracycline, quinolones and antiparasitic drugs was investigated in wild fish captured around salmon aquaculture pens in Cochamó, Region X, Chile. Residues of both antibiotics were found in the meta [corrected] of two species of wild fish that are consumed by humans, robalo (Elginops maclovinus) and cabrilla (Sebastes capensis) [corrected] These findings suggest that the antibiotic usage in salmon aquaculture in Chile has nvironmental implications that may affect human and animal health. More studies are needed in Chile to determine the relevance of these findings for human and animal health and the environment to regulate this use of antibiotics. PMID:17369965

  10. [Residues of tetracycline and quinolones in wild fish living around a salmon aquaculture center in Chile].

    PubMed

    Fortt Z, Antonia; Cabello C, Felipe; Buschmann R, Alejandro

    2007-02-01

    The presence of residues of tetracycline, quinolones and antiparasitic drugs was investigated in wild fish captured around salmon aquaculture pens in Cochamó, Region X, Chile. Residues of both antibiotics were found in the meta [corrected] of two species of wild fish that are consumed by humans, robalo (Elginops maclovinus) and cabrilla (Sebastes capensis) [corrected] These findings suggest that the antibiotic usage in salmon aquaculture in Chile has nvironmental implications that may affect human and animal health. More studies are needed in Chile to determine the relevance of these findings for human and animal health and the environment to regulate this use of antibiotics.

  11. Residual charge of niobium spheres

    SciTech Connect

    Phillips, J.D.

    1984-01-01

    In 1964, Gell-Mann and Zweig hypothesized that the particles inside nuclei are composed of quarks with electric charges of {plus minus} 1/3 e and {plus minus} 1/2 e. Since then, many searches have been made for stable fractional charges. The experiment described in a Millikan-type electrometer with a sample 10{sup 7} times heavier. A 0.28 mm diameter superconducting niobium ball is levitated magnetically between capacitor plates. The ball oscillates vertically on this magnetic spring and an electric field is applied at the oscillation frequency. The rate of change of the ball's oscillation amplitude is proportional to the force exerted on the ball by the electric field. The force on the ball is measured as a function of its position between the capacitor plates to discriminate against the background force due to the patch effect field gradient of the plates. There is one other background effect, due to the tilting of the ball's magnetic moment, which has sometimes manifested itself as a drift or occasionally as an offset in the measured force. An analysis presented in this thesis explains a mechanism for this effect and shows that we can eliminate it in our next run by spinning the ball about the vertical axis. The results are strong evidence for the existence of stable fractional charges of {plus minus} 1/3 e in matter. Out of 58 measurements on 20 balls, 9 have yielded results near - 1/3 e, 34 near 0, 13 near + 1/3e, one of the 0.19 e, and one of 0.44 e. Out of 38 repeat measurements, there have been 12 residual charge changes, 5 near - 1/3e and 7 near + 1/3 e.

  12. Gunshot residue preservation in seawater.

    PubMed

    Lindström, Anne-Christine; Hoogewerff, Jurian; Athens, Josie; Obertova, Zuzana; Duncan, Warwick; Waddell, Neil; Kieser, Jules

    2015-08-01

    Little is known about the persistence of gunshot residue (GSR) in soft tissue and bones during decomposition in marine environments. For a better understanding, qualitative and quantitative data were obtained on GSR retention on soft tissue and bony gunshot wounds (GSWs). A quantity of 36 fleshed and 36 defleshed bovine ribs were shot at contact range with 0.22 calibre hollow point ammunition using a Stirling 0.22 calibre long rifle. Bone specimens in triplicate were placed in three environments: submerged, intertidal and in supralittoral zone. Sets of triplicates were recovered on day 3, 10, 24 and 38, and analysed with scanning electron microscopy with energy dispersive X-ray spectrometry (SEM-EDX), and inductive coupled plasma mass spectrometry (ICP-MS). The SEM-EDX recorded GSR-indicative particles surrounding the bullet entrance on all bone types (fleshed and defleshed) in all environments throughout the study. GSR-unique particles were only detected on the supralittoral bones. The ICP-MS analysis showed faster GSR loss on submerged than intertidal and supralittoral defleshed specimens. Fleshed specimens showed a faster GSR loss on intertidal than submerged and supralittoral specimens. In conclusion, the GSR disappeared faster from submerged and intertidal than non-submerged specimens. The difference of detection of GSR between analysed specimens (defleshed versus fleshed) disappeared upon defleshing. This study highlights the potential of finding evidence of GSR in a submerged body and the potential of microscopic and analytical methods for examining suspected GSW in highly decomposed bodies in marine habitats. PMID:26115226

  13. Recycling of auto shredder residue.

    PubMed

    Nourreddine, Menad

    2007-01-31

    Currently, about 75% of end-of-life vehicle's (ELV) total weight is recycled in EU countries. The remaining 25%, which is called auto shredder residues (ASR) or auto fluff, is disposed of as landfill because of its complexity. It is a major challenge to reduce this percentage of obsolete cars. The European draft directive states that by the year 2006, only 15% of the vehicle's weight can be disposed of at landfill sites and by 2015, this will be reduced to 5%. The draft directive states that a further 10% can be incinerated. The quantities of shredder fluff are likely to increase in the coming years. This is because of the growing number of cars being scrapped, coupled with the increase in the amount of plastics used in cars. In Sweden, some current projects are focusing on recycling of ASR material. In this paper some different alternatives for using this material are reported. The hypothetical injection of ASR into a blast furnace concentrating on ASR's effect to some blast furnace (BF) parameters has been completed using a blast furnace mass balance model. As a result, in principle, ASR can be used as reducing agent in the BF process if certain conditions are met. The particle size of ASR material must be controlled to ensure optimal gasification of the material in the raceway. Regarding the chemical composition of ASR, the non-ferrous content can affect the pig iron quality, which is difficult to rectify at a later point. The most attractive recycling alternative is to use the products obtained from pyrolysis of ASR in appropriate metallurgical processes. PMID:16600493

  14. Binding site residues control inhibitor selectivity in the human norepinephrine transporter but not in the human dopamine transporter

    PubMed Central

    Andersen, Jacob; Ringsted, Kristoffer B.; Bang-Andersen, Benny; Strømgaard, Kristian; Kristensen, Anders S.

    2015-01-01

    The transporters for norepinephrine and dopamine (NET and DAT, respectively) constitute the molecular targets for recreational drugs and therapeutics used in the treatment of psychiatric disorders. Despite a strikingly similar amino acid sequence and predicted topology between these transporters, some inhibitors display a high degree of selectivity between NET and DAT. Here, a systematic mutational analysis of non-conserved residues within the extracellular entry pathway and the high affinity binding site in NET and DAT was performed to examine their role for selective inhibitor recognition. Changing the six diverging residues in the central binding site of NET to the complementary residues in DAT transferred a DAT-like pharmacology to NET, showing that non-conserved binding site residues in NET are critical determinants for inhibitor selectivity. In contrast, changing the equivalent residues in the central site of DAT to the corresponding residues in NET had modest effects on the same inhibitors, suggesting that non-conserved binding site residues in DAT play a minor role for selective inhibitor recognition. Our data points towards distinct structural determinants governing inhibitor selectivity in NET and DAT, and provide important new insight into the molecular basis for NET/DAT selectivity of therapeutic and recreational drugs. PMID:26503701

  15. Fighting the Drug War.

    ERIC Educational Resources Information Center

    The Journal of State Government, 1990

    1990-01-01

    All nine articles in this periodical issue focus on the theme of the war against illegal drug use, approaching the topic from a variety of perspectives. The articles are: "The Drug War: Meeting the Challenge" (Stanley E. Morris); "Ways to Fight Drug Abuse" (Bruce A. Feldman); "Treatment Key to Fighting Drugs" (Stan Lundine); "Patience and…

  16. What Are Drugs?

    ERIC Educational Resources Information Center

    Minnesota Police and Peace Officers Association.

    This guide for parents presents, in Laotian and English, information about drugs, drug use and abuse, and treatment for drug use. Most of the information is presented in question and answer form to give parents the information they need to answer their children's questions and help prevent drug use. The following sections are included: (1)…

  17. Drugs and Young People

    MedlinePlus

    Drug abuse is a serious public health problem. It affects almost every community and family in some way. Drug abuse in children and teenagers may pose a ... of young people may be more susceptible to drug abuse and addiction than adult brains. Abused drugs ...

  18. Drug-drug interactions between clopidogrel and novel cardiovascular drugs.

    PubMed

    Pelliccia, Francesco; Rollini, Fabiana; Marazzi, Giuseppe; Greco, Cesare; Gaudio, Carlo; Angiolillo, Dominick J

    2015-10-15

    The combination of aspirin and the thienopyridine clopidogrel is a cornerstone in the prevention of atherothrombotic events. These two agents act in concert to ameliorate the prothrombotic processes stimulated by plaque rupture and vessel injury complicating cardiovascular disease. Guidelines recommend the use of clopidogrel in patients with acute coronary syndromes and in those undergoing percutaneous coronary intervention, and the drug remains the most utilized P2Y12 receptor inhibitor despite the fact that newer antiplatelet agents are now available. In recent years, numerous studies have shown inconsistency in the efficacy of clopidogrel to prevent atherothrombotic events. Studies of platelet function testing have shown variability in the response to clopidogrel. One of the major reason for this phenomenon lies in the interaction between clopidogrel and other drugs that may affect clopidogrel absorption, metabolism, and ultimately its antiplatelet action. Importantly, these drug-drug interactions have prognostic implications, since patients with high on-treatment platelet reactivity associated with reduced clopidogrel metabolism have an increased risk of ischemia. Previous systematic reviews have focused on drug-drug interactions between clopidogrel and specific pharmacologic classes, such as proton pump inhibitors, calcium channel blockers, and statins. However, more recent pieces of scientific evidence show that clopidogrel may also interact with newer drugs that are now available for the treatment of cardiovascular patients. Accordingly, the aim of this review is to highlight and discuss recent data on drug-drug interactions between clopidogrel and third-generation proton pump inhibitors, pantoprazole and lansoprazole, statins, pitavastatin, and antianginal drug, ranolazine. PMID:26341013

  19. Nanotransporters for drug delivery.

    PubMed

    Lühmann, Tessa; Meinel, Lorenz

    2016-06-01

    Soluble nanotransporters for drugs can be profiled for targeted delivery particularly to maximize the efficacy of highly potent drugs while minimizing off target effects. This article outlines on the use of biological carrier molecules with a focus on albumin, various drug linkers for site specific release of the drug payload from the nanotransporter and strategies to combine these in various ways to meet different drug delivery demands particularly the optimization of the payload per nanotransporter.

  20. Agricultural residue availability in the United States.

    PubMed

    Haq, Zia; Easterly, James L

    2006-01-01

    The National Energy Modeling System (NEMS) is used by the Energy Information Administration (EIA) to forecast US energy production, consumption, and price trends for a 25-yr-time horizon. Biomass is one of the technologies within NEMS, which plays a key role in several scenarios. An endogenously determined biomass supply schedule is used to derive the price-quantity relationship of biomass. There are four components to the NEMS biomass supply schedule including: agricultural residues, energy crops, forestry residues, and urban wood waste/mill residues. The EIA's Annual Energy Outlook 2005 includes updated estimates of the agricultural residue portion of the biomass supply schedule. The changes from previous agricultural residue supply estimates include: revised assumptions concerning corn stover and wheat straw residue availabilities, inclusion of non-corn and non-wheat agricultural residues (such as barley, rice straw, and sugarcane bagasse), and the implementation of assumptions concerning increases in no-till farming. This article will discuss the impact of these changes on the supply schedule. PMID:16915628

  1. Monitoring tricyclazole residues in rice paddy watersheds.

    PubMed

    Padovani, Laura; Capri, Ettore; Padovani, Caterina; Puglisi, Edoardo; Trevisan, Marco

    2006-01-01

    Pesticide application to rice paddies may affect the quality of environmental resources such as groundwater and surface water. The distribution of residues of tricyclazole, an environmentally persistent fungicide used widely in Italy, was monitored in the network of surface water bodies surrounding the main rice production area in Italy. The location of monitoring sites was based on the potential risk for contamination with tricyclazole. This was determined as a function of the area of rice grown, the geographical distribution of rice crops susceptible to the pest, and sales of tricyclazole. Monitoring sites were also located to represent different spatial scales (farm, catchment and basin). For water samples taken shortly after application in July and August, the highest concentrations of tricyclazole were measured at the farm sites. However, residues were also detected at the catchment and basin scale. The 95% of the measured residue levels was below 9.80, 1.20 and 1.15 microg l(-1), at the farm, catchment and basin scales, respectively. In sediment, tricyclazole residues were detected in 12 out 176 samples collected with the 95% of the measured residue levels below the concentration of 0.03 mg kg(-1). Residues were sporadically detected in samples taken after the crop was harvested in November and December. Variables such as the scale of sampling, the season and the year, were significant in determining pesticide residue distribution. The type of water body was less significant.

  2. Antioxidant properties of roasted coffee residues.

    PubMed

    Yen, Wen-Jye; Wang, Bor-Sen; Chang, Lee-Wen; Duh, Pin-Der

    2005-04-01

    The antioxidant activity of roasted coffee residues was evaluated. Extraction with four solvents (water, methanol, ethanol, and n-hexane) showed that water extracts of roasted coffee residues (WERCR) produced higher yields and gave better protection for lipid peroxidation. WERCR showed a remarkable protective effect on oxidative damage of protein. In addition, WERCR showed scavenging of free radicals as well as the reducing ability and to bind ferrous ions, indicating that WERCR acts as both primary and secondary antioxidants. The HPLC analyses showed that phenolic acids (chlorogenic acid and caffeic acid) and nonphenolic compounds [caffeine, trigonelline, nicotinic acid, and 5-(hydroxymethyl)furfuraldehyde] remained in roasted coffee residues. These compounds showed a protective effect on a liposome model system. The concentrations of flavonoids and polyphenolic compounds in roasted coffee residues were 8,400 and 20,400 ppm, respectively. In addition, the Maillard reaction products (MRPs) remaining in roasted coffee residues were believed to show antioxidant activity. These data indicate that roasted coffee residues have excellent potential for use as a natural antioxidant source because the antioxidant compounds remained in roasted coffee residues. PMID:15796608

  3. Structure-based identification of catalytic residues.

    PubMed

    Yahalom, Ran; Reshef, Dan; Wiener, Ayana; Frankel, Sagiv; Kalisman, Nir; Lerner, Boaz; Keasar, Chen

    2011-06-01

    The identification of catalytic residues is an essential step in functional characterization of enzymes. We present a purely structural approach to this problem, which is motivated by the difficulty of evolution-based methods to annotate structural genomics targets that have few or no homologs in the databases. Our approach combines a state-of-the-art support vector machine (SVM) classifier with novel structural features that augment structural clues by spatial averaging and Z scoring. Special attention is paid to the class imbalance problem that stems from the overwhelming number of non-catalytic residues in enzymes compared to catalytic residues. This problem is tackled by: (1) optimizing the classifier to maximize a performance criterion that considers both Type I and Type II errors in the classification of catalytic and non-catalytic residues; (2) under-sampling non-catalytic residues before SVM training; and (3) during SVM training, penalizing errors in learning catalytic residues more than errors in learning non-catalytic residues. Tested on four enzyme datasets, one specifically designed by us to mimic the structural genomics scenario and three previously evaluated datasets, our structure-based classifier is never inferior to similar structure-based classifiers and comparable to classifiers that use both structural and evolutionary features. In addition to the evaluation of the performance of catalytic residue identification, we also present detailed case studies on three proteins. This analysis suggests that many false positive predictions may correspond to binding sites and other functional residues. A web server that implements the method, our own-designed database, and the source code of the programs are publicly available at http://www.cs.bgu.ac.il/∼meshi/functionPrediction.

  4. Simple approach for ranking structure determining residues.

    PubMed

    Luna-Martínez, Oscar D; Vidal-Limón, Abraham; Villalba-Velázquez, Miryam I; Sánchez-Alcalá, Rosalba; Garduño-Juárez, Ramón; Uversky, Vladimir N; Becerril, Baltazar

    2016-01-01

    Mutating residues has been a common task in order to study structural properties of the protein of interest. Here, we propose and validate a simple method that allows the identification of structural determinants; i.e., residues essential for preservation of the stability of global structure, regardless of the protein topology. This method evaluates all of the residues in a 3D structure of a given globular protein by ranking them according to their connectivity and movement restrictions without topology constraints. Our results matched up with sequence-based predictors that look up for intrinsically disordered segments, suggesting that protein disorder can also be described with the proposed methodology.

  5. Identification of residues by infrared spectroscopy

    SciTech Connect

    Barber, T.E.; Ayala, N.L.; Jin, Hong; Drumheller, C.T.

    1997-12-31

    Mid-infrared spectroscopy of surfaces can be a very powerful technique for the qualitative and quantitative analysis of surface residues. The goal of this work was to study the application of diffuse reflectance mid-infrared spectroscopy to the identification of pesticide, herbicide, and explosive residues on surfaces. A field portable diffuse reflectance spectrometer was used to collect the mid-infrared spectra of clean surfaces and contaminated surfaces. These spectra were used as calibration sets to develop automated data analysis to classify or to identify residues on samples. In this presentation, the instrumentation and data process algorithms will be discussed.

  6. Simple approach for ranking structure determining residues

    PubMed Central

    Luna-Martínez, Oscar D.; Vidal-Limón, Abraham; Villalba-Velázquez, Miryam I.; Sánchez-Alcalá, Rosalba; Garduño-Juárez, Ramón; Uversky, Vladimir N.

    2016-01-01

    Mutating residues has been a common task in order to study structural properties of the protein of interest. Here, we propose and validate a simple method that allows the identification of structural determinants; i.e., residues essential for preservation of the stability of global structure, regardless of the protein topology. This method evaluates all of the residues in a 3D structure of a given globular protein by ranking them according to their connectivity and movement restrictions without topology constraints. Our results matched up with sequence-based predictors that look up for intrinsically disordered segments, suggesting that protein disorder can also be described with the proposed methodology. PMID:27366642

  7. Diazinon residues in insects from sprayed tobacco

    USGS Publications Warehouse

    Stromborg, K.L.; Beyer, W.N.; Kolbe, E.

    1982-01-01

    Pooled samples of tobacco hornworms collected from a field sprayed with 0.84 kg/ha of diazinon were analyzed for residues at various intervals after application. No residues of the toxic metabolite diazoxon were detected (sensitivity 0.5 ppm) in any sample. Only one sample exceeded 1.0 ppm of the parent compound and was collected 4 hours after spraying. Residues declined over time (P<0.01) and none were detected (sensitivity 0.1 ppm) 18 days after spraying. the potential hazard to birds eating these insects appeared to be minimal.

  8. Residual stresses in injection molded products

    NASA Astrophysics Data System (ADS)

    Jansen, K. M. B.

    2015-12-01

    During the molding process residual stresses are formed due to thermal contraction during cooling as well as the local pressure history during solidification. In this paper a simple analytical model is reviewed which relates residual stresses, product shrinkage as well as warpage to the temperature and pressure histories during molding. Precise excimer laser layer removal measurements were performed to verify the predicted residual stress distributions. In addition, detailed shrinkage and warpage measurements on a large series of polymers and for different molding conditions were performed and are shown to compare well with the model predictions.

  9. Food-Drug Interactions

    PubMed Central

    Bushra, Rabia; Aslam, Nousheen; Khan, Arshad Yar

    2011-01-01

    The effect of drug on a person may be different than expected because that drug interacts with another drug the person is taking (drug-drug interaction), food, beverages, dietary supplements the person is consuming (drug-nutrient/food interaction) or another disease the person has (drug-disease interaction). A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own. These interactions may occur out of accidental misuse or due to lack of knowledge about the active ingredients involved in the relevant substances. Regarding food-drug interactions physicians and pharmacists recognize that some foods and drugs, when taken simultaneously, can alter the body's ability to utilize a particular food or drug, or cause serious side effects. Clinically significant drug interactions, which pose potential harm to the patient, may result from changes in pharmaceutical, pharmacokinetic, or pharmacodynamic properties. Some may be taken advantage of, to the benefit of patients, but more commonly drug interactions result in adverse drug events. Therefore it is advisable for patients to follow the physician and doctors instructions to obtain maximum benefits with least food-drug interactions. The literature survey was conducted by extracting data from different review and original articles on general or specific drug interactions with food. This review gives information about various interactions between different foods and drugs and will help physicians and pharmacists prescribe drugs cautiously with only suitable food supplement to get maximum benefit for the patient. PMID:22043389

  10. Herb-drug, food-drug, nutrient-drug, and drug-drug interactions: mechanisms involved and their medical implications.

    PubMed

    Sørensen, Janina Maria

    2002-06-01

    Adverse drug reactions (ADRs) and iatrogenic diseases have been identified as significant factors responsible for patient morbidity and mortality. Significant studies on drug metabolism in humans have been published during the last few years, offering a deeper comprehension of the mechanisms underlying adverse drug reactions and interactions. More understanding of these mechanisms, and of recent advances in laboratory technology, can help to evaluate potential drug interactions when drugs are prescribed concurrently. Increasing knowledge of interindividual variation in drug breakdown capacity and recent findings concerning the influence of environment, diet, nutrients, and herbal products can be used to reduce ADRs and iatrogenic diseases. Reviewed data suggest that drug treatment should be increasingly custom tailored to suit the individual patient and that appropriately co-prescribed diet and herbal remedies, could increase drug efficacy and lessen drug toxicity. This review focuses mainly on recently published research material. The cytochrome p450 enzymes, their role in metabolism, and their mechanisms of action are reviewed, and their role in drug-drug interactions are discussed. Drug-food and drug-herb interactions have garnered attention. Interdisciplinary communication among medical herbalists, medical doctors, and dietetic experts needs to be improved and encouraged. Internet resources for obtaining current information regarding drug-drug, drug-herb, and drug-nutrient interactions are provided. PMID:12165187

  11. Determination of sulfonamide residues in eggs by liquid chromatography.

    PubMed

    Furusawa, Naoto

    2002-01-01

    A method was developed for determining residual sulfonamide antibacterials such as sulfamethazine (SMZ), sulfamonomethoxine (SMM), sulfadimethoxine (SDM), and sulfaquinoxaline (SQ) in eggs using liquid chromatography with a photodiode array detector. The spiked and blank samples were cleaned up by using an Ultrafree-MC/PL centrifugal ultrafiltration unit. A Mightysil RP-4 GP column and a mobile phase of 28% (v/v) ethanol-H2O with a photodiode array detector were used for the determination. Average recoveries from eggs spiked with each drug at 0.1, 0.2, 0.4, and 1.0 ppm were > or = 80.9%, with relative standard deviations between 1.3 and 4.7%. The limits of quantitation were 0.060 ppm for SMZ, 0.045 for SMM, 0.044 for SDM, and 0.093 for SQ. The analysis of one sample required < 30 min and < 5 mL ethanol as solvent. PMID:12180677

  12. Analysis of Food Contaminants, Residues, and Chemical Constituents of Concern

    NASA Astrophysics Data System (ADS)

    Ismail, Baraem; Reuhs, Bradley L.; Nielsen, S. Suzanne

    The food chain that starts with farmers and ends with consumers can be complex, involving multiple stages of production and distribution (planting, harvesting, breeding, transporting, storing, importing, processing, packaging, distributing to retail markets, and shelf storing) (Fig. 18.1). Various practices can be employed at each stage in the food chain, which may include pesticide treatment, agricultural bioengineering, veterinary drug administration, environmental and storage conditions, processing applications, economic gain practices, use of food additives, choice of packaging material, etc. Each of these practices can play a major role in food quality and safety, due to the possibility of contamination with or introduction (intentionally and nonintentionally) of hazardous substances or constituents. Legislation and regulation to ensure food quality and safety are in place and continue to develop to protect the stakeholders, namely farmers, consumers, and industry. [Refer to reference (1) for information on regulations of food contaminants and residues.

  13. Do drug offences matter?

    PubMed

    Gordon, A M

    1978-07-15

    Drug offences in addicts are often thought to indicate little more than continued dependency. In a four-year follow-up study of 60 men attending a drug clinic a history of repeated convictions for drug offences was found to be strongly related to patterns of delinquency. The following variables were associated with a history of repeated drug offences: a higher conviction rate for "non-drug" offences; younger age at first conviction; conviction preceding drug use; convictions for offences of sex and violence; longer prison sentences; and regular narcotic use and continued dependency at follow-up. Receiving a clinic prescription was not associated with a lower incidence of drug offences. Repeated drug offences identified a subgroup of drug users who were characterised by extensive sociopathic behaviour. Such offences should not be dismissed as an unavoidable, unimportant part of addiction. PMID:678840

  14. Recovery of transuranics from process residues

    SciTech Connect

    Gray, J.H.; Gray, L.W.

    1987-01-01

    Process residues are generated at both the Rocky Flats Plant (RFP) and the Savannah River Plant (SRP) during aqueous chemical and pyrochemical operations. Frequently, process operations will result in either impure products or produce residues sufficiently contaminated with transuranics to be nondiscardable as waste. Purification and recovery flowsheets for process residues have been developed to generate solutions compatible with subsequent Purex operations and either solid or liquid waste suitable for disposal. The ''scrub alloy'' and the ''anode heel alloy'' are examples of materials generated at RFP which have been processed at SRP using the developed recovery flowsheets. Examples of process residues being generated at SRP for which flowsheets are under development include LECO crucibles and alpha-contaminated hydraulic oil.

  15. Differential Spectroscopic Imaging of Particulate Explosives Residue

    SciTech Connect

    Bernacki, Bruce E.; Ho, Nicolas

    2008-04-01

    We present experimental results showing transmission and reflection imaging of approximately 100 microgram quantities of particulate explosives residue using a commercial uncooled microbolometer infrared camera and CO2 laser differential wavelength illumination.

  16. Ceramic colorant from untreated iron ore residue.

    PubMed

    Pereira, Oscar Costa; Bernardin, Adriano Michael

    2012-09-30

    This work deals with the development of a ceramic colorant for glazes from an untreated iron ore residue. 6 mass% of the residue was added in suspensions (1.80 g/cm(3) density and 30s viscosity) of white, transparent and matte glazes, which were applied as thin layers (0.5mm) on engobeb and not fired ceramic tiles. The tiles were fired in laboratory roller kiln in a cycle of 35 min and maximum temperatures between 1050 and 1180°C. The residue and glazes were characterized by chemical (XRF) and thermal (DTA and optical dilatometry) analyses, and the glazed tiles by colorimetric and XRD analyses. The results showed that the colorant embedded in the transparent glaze results in a reddish glaze (like pine nut) suitable for the ceramic roof tile industry. For the matte and white glazes, the residue has changed the color of the tiles with temperature. PMID:22795839

  17. SAR impulse response with residual chirps.

    SciTech Connect

    Doerry, Armin Walter

    2009-06-01

    A Linear Frequency-Modulated (LFM) chirp is a function with unit amplitude and quadratic phase characteristic. In a focused Synthetic Aperture Radar (SAR) image, a residual chirp is undesired for targets of interest, as it coarsens the manifested resolution. However, for undesired spurious signals, a residual chirp is often advantageous because it spreads the energy and thereby diminishes its peak value. In either case, a good understanding of the effects of a residual LFM chirp on a SAR Impulse Response (IPR) is required to facilitate system analysis and design. This report presents an analysis of the effects of a residual chirp on the IPR. As reference, there is a rich body of publications on various aspects of LFM chirps. A quick search reveals a plethora of articles, going back to the early 1950s. We mention here purely as trivia one of the earlier analysis papers on this waveform by Klauder, et al.

  18. Arabian crude-oil residues evaluated

    SciTech Connect

    Ali, M.F.; Bukhari, A.; Hasan, M.; Saleem, M.

    1985-08-12

    This article evaluates detailed physical and chemical characteristics for four important Saudi Arabian resids. Petroleum residues are composed of a mixture of large and complex hydrocarbon molecules along with one or more heteroatoms such as sulfur, oxygen, nitrogen, vanadium, and nickel. The amount of residue and its physical and chemical composition depend on the source of the crude oil and methods of processing. Residues from four Saudi Arabian crude oils produced by the Arabian American Oil Co. (Aramco) were evaluated. The crude oils are 38.5 degrees API Arabian Extra Light, 33.8 degrees API Arabian Light, 30.4 degrees Api Arabian Medium, and 28.03 degrees API Arabian Heavy. Results are presented and residue preparation, and physical and chemical characteristics are analyzed.

  19. Properties of Rasch residual fit statistics.

    PubMed

    Wu, Margaret; Adams, Richard J

    2013-01-01

    This paper examines the residual-based fit statistics commonly used in Rasch measurement. In particular, the paper analytically examines some of the theoretical properties of the residual-based fit statistics with a view to establishing the inferences that can be made using these fit statistics. More specifically, the relationships between the distributional properties of the fit statistics and sample size are discussed; some research that erroneously concludes that residual-based fit statistics are unstable is reviewed; and finally, it is analytically illustrated that, for dichotomous items, residual-based fit statistics provide a measure of the relative slope of empirical item characteristic curves. With a clear understanding of the theoretical properties of the fit statistics, the use and limitations of these statistics can be placed in the right light.

  20. Ceramic colorant from untreated iron ore residue.

    PubMed

    Pereira, Oscar Costa; Bernardin, Adriano Michael

    2012-09-30

    This work deals with the development of a ceramic colorant for glazes from an untreated iron ore residue. 6 mass% of the residue was added in suspensions (1.80 g/cm(3) density and 30s viscosity) of white, transparent and matte glazes, which were applied as thin layers (0.5mm) on engobeb and not fired ceramic tiles. The tiles were fired in laboratory roller kiln in a cycle of 35 min and maximum temperatures between 1050 and 1180°C. The residue and glazes were characterized by chemical (XRF) and thermal (DTA and optical dilatometry) analyses, and the glazed tiles by colorimetric and XRD analyses. The results showed that the colorant embedded in the transparent glaze results in a reddish glaze (like pine nut) suitable for the ceramic roof tile industry. For the matte and white glazes, the residue has changed the color of the tiles with temperature.

  1. 77 FR 9528 - Animal Drugs, Feeds, and Related Products; N-Methyl-2-Pyrrolidone; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-17

    ... Register of November 25, 2011 (76 FR 72617), codifying a method of detection for residues of n-methyl-2....hhs.gov . SUPPLEMENTARY INFORMATION: In the Federal Register of November 25, 2011 (76 FR 72617), FDA... HUMAN SERVICES Food and Drug Administration 21 CFR Part 500 Animal Drugs, Feeds, and Related Products;...

  2. Determination of trimethoprim and sulphadoxine residues in porcine tissues and plasma.

    PubMed Central

    Boison, J O; Nachilobe, P; Cassidy, R; Keng, L; Thacker, P A; Peacock, A; Fesser, A C; Lee, S; Korsrud, G O; Bulmer, W S

    1996-01-01

    Healthy gilts and market-ready hogs were administered a single intramuscular (IM) injection of Borgal, a commercial formulation of trimethoprim-sulfadoxine (TMP-SDX), once or twice daily. The objectives were to determine if a newly-developed high-performance liquid chromatographic (HPLC) method would be suitable for measuring the residual concentrations of TMP in the plasma of these live animals, and to determine if the administration of this veterinary drug would leave measurable residues in their plasma and tissues at slaughter. Plasma and tissue concentrations of SDX and TMP from these animals were determined over a period of 14 d using thin-layer chromatography/densitometry (TLCD), and the newly-developed HPLC method, respectively. The lowest detectable limit (LDL) for SDX in plasma and tissue was 20 ppb by TLCD. The HPLC method had a LDL of 5 ppb for TMP in plasma and tissue. Both methods were then used to provide baseline data on the absorption and depletion of TMP and SDX from these healthy animals. It was observed that both TMP and SDX were readily absorbed into the blood and tissues, but TMP was eliminated much faster than SDX. No TMP residues were detected in the plasma of any of the gilts at and beyond 21 h after drug administration. Also, no TMP residues were detected in the plasma of any of the market-ready hogs 24 h after drug administration at either the label dose or twice the label dose. Sulfadoxine residues at concentrations above the maximum residue limit (MRL) of 100 ppb were, however, detected in the plasma, muscle, kidney, liver, and injection sites of hogs slaughtered 1 and 3 d after a single IM administration at the label dose. Although SDX residues were still detectable in the lungs, kidney, liver and plasma of some hogs 10 d after administration of the label dose and twice the label dose, these were below the MRL. Postmortem examination revealed necrosis and inflammation at the injection sites, but no visible deposits of the injected drug

  3. Drugs and drug administration in extreme environments.

    PubMed

    Küpper, Thomas E A H; Schraut, Bettina; Rieke, Burkhard; Hemmerling, Arnica-Verena; Schöffl, Volker; Steffgen, Juergen

    2006-01-01

    Emergency medicine must often cope with harsh climates far below freezing point or high temperatures, and sometimes, an alternative to the normal route of drug administration is necessary. Most of this information is not yet published. Therefore, we summarized the information about these topics for most drugs used in medical emergencies by combining literature research with extensive personal communications with the heads of the drug safety departments of the companies producing these drugs. Most drugs can be used after temperature stress of limited duration. Nevertheless, we recommend replacing them at least once per year or after extreme heat. Knowledge about drugs used in extreme environments will be of increasing importance for medical personnel because in an increasingly mobile society, more and more people, and especially elderly -often with individual medical risks-travel to extreme regions such as tropical or arctic regions or to high altitude, and some of them need medical care during these activities. Because of this increasing need to use drugs in harsh climates (tourism, expeditions, peace corps, military, etc) the actual International Congress of Harmonization recommendations should be added with stability tests at +50 degrees C, freezing and oscillating temperatures, and UV exposure to simulate the storage of the drugs at "outdoor conditions." PMID:16412107

  4. Discontinued drugs in 2010: cardiovascular drugs.

    PubMed

    Zhao, Hong-ping; Zhang, Xu-song; Xiang, Bing-ren

    2011-10-01

    This perspective is a paper discussing drugs dropped from clinical development in the previous years. Specifically, this paper focuses on 16 cardiovascular drugs discontinued in 2010 after reaching Phase I - III clinical trials. Information for this perspective is mainly derived from a search of Pharmaprojects. PMID:21870899

  5. Quantitation of residual mouse DNA in monoclonal antibody based products.

    PubMed

    Per, S R; Aversa, C R; Sito, A F

    1990-01-01

    The identification and characterization of cell substrates and testing of bulk and final products is an important issue which must be addressed by manufacturers. In view of the fact that hundreds of applications for Investigational New Drugs (IND) have been submitted over the past few years, there is an obvious need for testing of these products. Detection of DNA by molecular hybridization has been used for various applications including the quantitation and characterization of DNA in biological products. We have developed a precise assay based on hybridization for the detection and quantitation of residual genomic DNA. In order to reduce protein interference, a specific pretreatment method for isolation of DNA in monoclonal antibody based products was implemented. We have used the assay to evaluate levels of contaminating DNA in prepared lots of monoclonal antibodies. Validation experiments demonstrated a sensitivity below 10 pg DNA using nick-translated 32P-labelled genomic DNA probes. The assay allows accurate quantitation of residual DNA in biologics.

  6. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  7. GLC determination of quinaldine residue in fish

    USGS Publications Warehouse

    Allen, J.L.; Sills, J.B.

    1970-01-01

    A procedure for the determination of quinaldine residue in various fish tissues is described. Homogenized tissues are extracted wi th hexane-ethyl ether, the extracts are concentrated by partitioning through O.IN sulfuric acid, and the residues are measured by alkali Harne ionization gas chromatography. Muscle tissues containing from 0.01 to 10.0 ppm quinaldine were successfully analyzed with recoveries from 75 to 100%.

  8. Rapid and Sensitive Chemiluminescent Enzyme Immunoassay for the Determination of Neomycin Residues in Milk.

    PubMed

    Luo, Peng Jie; Zhang, Jian Bo; Wang, Hua Li; Chen, Xia; Wu, Nan; Zhao, Yun Feng; Wang, Xiao Mei; Zhang, Hong; Zhang, Ji Yue; Zhu, Lei; Jiang, Wen Xiao

    2016-05-01

    Immunoassays greatly contribute to veterinary drug residue analysis. However, there are few reports on detecting neomycin residues by immunoassay. Here, a rapid and sensitive chemiluminescent enzyme immunoassay (CLIEA) was successfully developed for neomycin residue analysis. CLIEA demonstrated good cross-reactivity for neomycin, and the IC50 value was 2.4 ng/mL in buffer. The average recovery range was 88.5%-105.4% for spiked samples (10, 50, and 100 μg/kg), and the coefficient of variation was in the range of 7.5%-14.5%. The limit of detection of CLEIA was 9.4 μg/kg, and this method was compared with the liquid chromatography-tandem mass spectrometry method using naturally contaminated samples, producing a correlation coefficient of >0.95. We demonstrate a reliable CLIEA for the rapid screening of neomycin in milk. PMID:27353712

  9. Trace metal residues in shellfish from Maryland waters, 1976-1980

    SciTech Connect

    Eisenberg, M.; Topping, J.J.

    1984-10-01

    Levels of seven heavy metal residues, arsenic, cadmium, chromium, copper, lead, mercury and zinc were monitored in samples of the American oyster (Crassostrea virginica), the soft shell clam (Mya arenaria), the hard shell clam (Mercenaria mercenaria) and the blue crab (Callinectes sapidus). The study was conducted from 1976 through 1980. In cases where the Food and Drug Administration has established action levels, mean and median yearly values were significantly below these levels. In cases where no action level exists, heavy metal residues in the shellfish samples were well below levels which are generally regarded as safe. No significant yearly trends in heavy metal residues were discovered. Apparent increases in arsenic levels merit further study. 22 references, 1 figure, 3 tables.

  10. An Intriguing Correlation Based on the Superimposition of Residue Pairs with Inhibitors that Target Protein-Protein Interfaces

    PubMed Central

    Nakadai, Masakazu; Tomida, Shuta; Sekimizu, Kazuhisa

    2016-01-01

    Druggable sites on protein-protein interfaces are difficult to predict. To survey inhibitor-binding sites onto which residues are superimposed at protein-protein interfaces, we analyzed publicly available information for 39 inhibitors that target the protein-protein interfaces of 8 drug targets. By focusing on the differences between residues that were superimposed with inhibitors and non-superimposed residues, we observed clear differences in the distances and changes in the solvent-accessible surface areas (∆SASA). Based on the observation that two or more residues were superimposed onto inhibitors in 37 (95%) of 39 protein-inhibitor complexes, we focused on the two-residue relationships. Application of a cross-validation procedure confirmed a linear negative correlation between the absolute value of the dihedral angle and the sum of the ∆SASAs of the residues. Finally, we applied the regression equation of this correlation to four inhibitors that bind to new sites not bound by the 39 inhibitors as well as additional inhibitors of different targets. Our results shed light on the two-residue correlation between the absolute value of the dihedral angle and the sum of the ∆SASA, which may be a useful relationship for identifying the key two-residues as potential targets of protein-protein interfaces. PMID:26730437

  11. PINGU: PredIction of eNzyme catalytic residues usinG seqUence information

    PubMed Central

    Pai, Priyadarshini P.; Ranjani, S. S. Shree; Mondal, Sukanta

    2015-01-01

    Identification of catalytic residues can help unveil interesting attributes of enzyme function for various therapeutic and industrial applications. Based on their biochemical roles, the number of catalytic residues and sequence lengths of enzymes vary. This article describes a prediction approach (PINGU) for such a scenario. It uses models trained using physicochemical properties and evolutionary information of 650 non-redundant enzymes (2136 catalytic residues) in a support vector machines architecture. Independent testing on 200 non-redundant enzymes (683 catalytic residues) in predefined prediction settings, i.e., with non-catalytic per catalytic residue ranging from 1 to 30, suggested that the prediction approach was highly sensitive and specific, i.e., 80% or above, over the incremental challenges. To learn more about the discriminatory power of PINGU in real scenarios, where the prediction challenge is variable and susceptible to high false positives, the best model from independent testing was used on 60 diverse enzymes. Results suggested that PINGU was able to identify most catalytic residues and non-catalytic residues properly with 80% or above accuracy, sensitivity and specificity. The effect of false positives on precision was addressed in this study by application of predicted ligand-binding residue information as a post-processing filter. An overall improvement of 20% in F-measure and 0.138 in Correlation Coefficient with 16% enhanced precision could be achieved. On account of its encouraging performance, PINGU is hoped to have eventual applications in boosting enzyme engineering and novel drug discovery. PMID:26261982

  12. Axial residual stresses in boron fibers

    NASA Technical Reports Server (NTRS)

    Behrendt, D. R.

    1978-01-01

    The axial residual stress distribution as a function of radius was determined from the fiber surface to the core including the average residual stress in the core. Such measurements on boron on tungsten (B/W) fibers show that the residual stresses for 102, 142, 203, and 366 micron diameter fibers were similar, being compressive at the surface and changing monotonically to a region of tensile within the boron. At approximately 25 percent of the original radius, the stress reaches a maximum tensile stress of about 860 mn/sq.m and then decreases to a compressive stress near the tungsten boride core. Data were presented for 203 micron diameter B/W fibers that show annealing above 900 C reduces the residual stresses. A comparison between 102 micron diameter B/W and boron on carbon (b/C) shows that the residual stresses were similar in the outer regions of the fibers, but that large differences near and in the core were observed. The effects of these residual stresses on the fracture of boron fibers were discussed.

  13. Residual caries detection using visible fluorescence.

    PubMed

    Lennon, A M; Buchalla, W; Switalski, L; Stookey, G K

    2002-01-01

    This study investigated the ability of a new fluorescence method to detect residual caries in vitro. Gross caries was removed from 40 teeth with D2 caries. Samples were excited with violet-blue light and viewed through a 530-nm high-pass filter. Residual caries (orange-red fluorescing dentin) was detected in all samples. Further tooth substance was removed from half of the samples until no residual caries was detectable using the new method. Half of the samples remained untreated. A blinded examiner checked all samples for residual caries using DIAGNOdent, a visual tactile examination, and Caries Detector dye. Presence or absence of residual caries in each sample was determined using a fluorescent nucleic acid stain in conjunction with confocal microscopy. The new method, Visible Fluorescence, had the greatest sensitivity, specificity, percent correct score and predictive values of any of the methods tested. The new method had significantly higher percent correct score than any of the other methods and significantly higher specificity than visual tactile and Caries Detector. It was concluded that Visible Fluorescence is an improvement on the currently available aids for residual caries detection.

  14. Method for residual household waste composition studies.

    PubMed

    Sahimaa, Olli; Hupponen, Mari; Horttanainen, Mika; Sorvari, Jaana

    2015-12-01

    The rising awareness of decreasing natural resources has brought forward the idea of a circular economy and resource efficiency in Europe. As a part of this movement, European countries have identified the need to monitor residual waste flows in order to make recycling more efficient. In Finland, studies on the composition of residual household waste have mostly been conducted using different methods, which makes the comparison of the results difficult. The aim of this study was to develop a reliable method for residual household waste composition studies. First, a literature review on European study methods was performed. Also, 19 Finnish waste composition studies were compared in order to identify the shortcomings of the current Finnish residual household waste composition data. Moreover, the information needs of different waste management authorities concerning residual household waste were studied through a survey and personal interviews. Stratification, sampling, the classification of fractions and statistical analysis were identified as the key factors in a residual household waste composition study. The area studied should be divided into non-overlapping strata in order to decrease the heterogeneity of waste and enable comparisons between different waste producers. A minimum of six subsamples, each 100 kg, from each stratum should be sorted. Confidence intervals for each waste category should be determined in order to evaluate the applicability of the results. A new three-level classification system was created based on Finnish stakeholders' information needs and compared to four other European waste composition study classifications.

  15. Detecting organic gunpowder residues from handgun use

    NASA Astrophysics Data System (ADS)

    MacCrehan, William A.; Ricketts, K. Michelle; Baltzersen, Richard A.; Rowe, Walter F.

    1999-02-01

    The gunpowder residues that remain after the use of handguns or improvised explosive devices pose a challenge for the forensic investigator. Can these residues be reliably linked to a specific gunpowder or ammunition? We investigated the possibility by recovering and measuring the composition of organic additives in smokeless powder and its post-firing residues. By determining gunpowder additives such as nitroglycerin, dinitrotoluene, ethyl- and methylcentralite, and diphenylamine, we hope to identify the type of gunpowder in the residues and perhaps to provide evidence of a match to a sample of unfired powder. The gunpowder additives were extracted using an automated technique, pressurized fluid extraction (PFE). The conditions for the quantitative extraction of the additives using neat and solvent-modified supercritical carbon dioxide were investigated. All of the major gunpowder additives can be determined with baseline resolution using capillary electrophoresis (CE) with a micellar agent and UV absorbance detection. A study of candidate internal standards for use in the CE method is also presented. The PFE/CE technique is used to evaluate a new residue sampling protocol--asking shooters to blow their noses. In addition, an initial investigation of the compositional differences among unfired and post-fired .22 handgun residues is presented.

  16. Method for residual household waste composition studies.

    PubMed

    Sahimaa, Olli; Hupponen, Mari; Horttanainen, Mika; Sorvari, Jaana

    2015-12-01

    The rising awareness of decreasing natural resources has brought forward the idea of a circular economy and resource efficiency in Europe. As a part of this movement, European countries have identified the need to monitor residual waste flows in order to make recycling more efficient. In Finland, studies on the composition of residual household waste have mostly been conducted using different methods, which makes the comparison of the results difficult. The aim of this study was to develop a reliable method for residual household waste composition studies. First, a literature review on European study methods was performed. Also, 19 Finnish waste composition studies were compared in order to identify the shortcomings of the current Finnish residual household waste composition data. Moreover, the information needs of different waste management authorities concerning residual household waste were studied through a survey and personal interviews. Stratification, sampling, the classification of fractions and statistical analysis were identified as the key factors in a residual household waste composition study. The area studied should be divided into non-overlapping strata in order to decrease the heterogeneity of waste and enable comparisons between different waste producers. A minimum of six subsamples, each 100 kg, from each stratum should be sorted. Confidence intervals for each waste category should be determined in order to evaluate the applicability of the results. A new three-level classification system was created based on Finnish stakeholders' information needs and compared to four other European waste composition study classifications. PMID:26337965

  17. Comparative ecotoxicology of halogenated hydrocarbon residues.

    PubMed

    Winteringham, F P

    1977-12-01

    The term ecotoxicology is adopted in the sense of a comparative and integrated study of the undesirable effects of trace contaminants on the range of fauna and flora of an "ecosystem" or of a defined part or unit thereof. The importance of population changes over long periods of time is stressed. Sources, usage, and global trends of representative halogenated hydrocarbon (HHC) residues which appear as trace contaminants of environment, food, and living organisms are briefly compared: industrial solvents and intermediates, chlorofluoromethanes as an atmospheric pollutant, methyl bromide as a food and soil residue, HCH (hexachlorobenzene) as a fungicide residue, DDT, lindane (gamma-hexachlorocyclohexane), and dieldrin as insecticide residues, and polychlorinated biphenyls (PCBs) as industrial contaminants. A simple mathematical approach to the problem of relating inputs, persistence, and steady-state residue levels is explained. Persistence and biodegradation of representative compounds are compared. Attention is drawn to the persistence of hexachlorobenzene, the p,p'-dichlorodiphenyl- and hexachlorocyclopentadiene-derived moities of HHC residues. Ecotoxicological effects and their implications are discussed comparatively under the indirect effects of atmospheric pollutants and direct and indirect effects of trace contaminants of soil and aquatic ecosystems. Some conclusions related to research and "impact monitoring" are drawn.

  18. 40 CFR 180.432 - Lactofen; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Lactofen; tolerances for residues. (a) Tolerances are established for residues of the herbicide lactofen, 1... residues of the herbicide, lactofen, 1-(carboethoxy)ethyl 5- -2- nitrobenzoate, in or on the following...

  19. Tetracycline residues in porcine stomach after administration via drinking water on a swine farm.

    PubMed

    Lindquist, Danielle; Wu, Huali; Mason, Sharon; Yeatts, Jim; Brooks, Jim; Barlow, Beth; Schill, Kaitlyn; Baynes, Ronald

    2014-01-01

    Tetracycline is a broad-spectrum antibiotic used to treat infections in swine. The maximum residue levels of tetracycline in pork stomach tissue in Russia, Europe, and the United States are 10, 200, and 2,000 ppb, respectively. This difference in accepted safety levels may be the reason why stomach tissues that the United States exports continue to be residue violators in overseas markets. In this study, 30 pigs at two different stages of production (weanling and finisher) were treated with tetracycline at 22 mg/kg of body weight per day for a total of 5 days via a water medicator. Blood samples were collected at 0, 72, 78, 96, and 102 h after the start of medication. The medication was stopped at 120 h, and blood samples were again collected at 126, 144, 168, 192, and 216 h after exposure. Five animals were slaughtered for stomach tissue 0, 24, 48, 96, and 192 h after the drug was flushed from the water line. All blood and tissue samples were analyzed by high-performance liquid chromatography-UV methods. The tetracycline levels in plasma were below the level of detection after the U.S.-labeled withdrawal time of 4 days. The stomach tissue residues averaged 671.72, 330.31, 297.77, 136.36, and 268.08 ppb on withdrawal days 0, 1, 2, 4, and 8, respectively. Using the U.S. Food and Drug Administration tolerance limit method and a population-based pharmacokinetic model with Monte Carlo simulation, a withdrawal interval was estimated. This study demonstrated that tetracycline residues are still detectable in the stomach tissues after the established United States withdrawal time of 4 days. These residue levels may explain why stomach tissues tested in Russia and Europe show positive residues for tetracycline, even though the meat may pass inspection here in the United States prior to export.

  20. Problems of positive list system revealed by survey of pesticide residue in food.

    PubMed

    Iwasaki, Mariko; Sato, Itaru; Jin, Yihe; Saito, Norimitsu; Tsuda, Shuji

    2007-05-01

    The positive list system became effective from May 29, 2006 to improve the regulation of residual agricultural chemicals (pesticides, feed additives and veterinary drugs) in foods. In accordance with the system, we investigated pesticide residues in 50 agricultural products purchased in Morioka city from March to November 2006. Analyses were performed according to the "Multiresidue Method for Agricultural Chemicals by GC/MS", the Notice of the Ministry of Health, Labour and Welfare. Five pesticides and two non-agricultural chemicals were detected from 16 samples. Ortho-phenylphenol (OPP) was detected from 8 samples: immature pea, snap bean, kiwi, plain-boiled bamboo shoot, mango, white asparagus, lemon and domestic shiitake mushroom. Maximum residue limits (MRLs) have not been established for these products, and they exceeded the uniform level of 0.01 ppm. DDT was detected from Philippines banana (0.30 ppm) and Korean paprika (0.45 ppm). The residual level in Philippines banana was lower than the MRL, but Korean paprika exceeded its MRL. Chlorpyrifos, Thiabendazole and Imazaril were detected from citrus imported from the U.S.A., but their residue levels were lower than the respective MRLs. Aniline and 2-pyrrolidone were detected from several imported products. These two may not be regulated by the positive list system because they are not agricultural chemicals, although their derivatives are used as pesticides or veterinary drugs. Three problems have been revealed from this survey: 1) application of the uniform level to minor agricultural products, 2) residues of non-agricultural chemicals whose toxicity is uncertain, 3) metabolites of agricultural chemicals, which are also regulated by the positive list system, have not been clearly defined. PMID:17538241

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

    PubMed

    Kimera, Zuhura I; Mdegela, Robinson H; Mhaiki, Consolatha J N; Karimuribo, Esron D; Mabiki, Faith; Nonga, Hezron E; Mwesongo, James

    2015-01-01

    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. PMID:26842366

  2. Investigation of the persistence of closantel residues in bovine milk following lactating-cow and dry-cow treatments and its migration into dairy products.

    PubMed

    Power, Clare; Sayers, Riona; O'Brien, Bernadette; Clancy, Clare; Furey, Ambrose; Jordan, Kieran; Danaher, Martin

    2013-09-11

    Closantel is a veterinary drug used to treat liver fluke in cattle and sheep. A provisional maximum residue limit (MRL) of 45 μg/kg in milk has been set by the European Union. The purpose of this study was to investigate the persistence of closantel residues in milk and the migration of residues into milk products. Following dry-cow treatment, residues ranged from undetectable to 8.7 μg/kg at the first milking. Following lactating-cow treatment, residues detected ranged from 278 to 482 μg/kg at day 1 post-treatment and were detectable above the MRL for 52 days and detectable for 198 days. At day 2 and day 23 post-treatment, the milk was collected and dairy products manufactured. Closantel residues concentrated in the cheese, butter, and skim milk powder. The results indicate that closantel is best used as a dry-cow treatment.

  3. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices.

  4. Adverse drug reactions in veterinary patients associated with drug transporters.

    PubMed

    Mealey, Katrina L

    2013-09-01

    For many drugs used in veterinary practice, plasma and tissue concentrations are highly dependent on the activity of drug transporters. This article describes how functional changes in drug transporters, whether mediated by genetic variability or drug-drug interactions, affect drug disposition and, ultimately, drug safety and efficacy in veterinary patients. A greater understanding of species, breed, and individual (genetic) differences in drug transporter function, as well as drug-drug interactions involving drug transporters, will result in improved strategies for drug design and will enable veterinarians to incorporate individualized medicine in their practices. PMID:23890239

  5. Students and Drug Abuse

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Introduction to "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  6. Antidiarrheal drug overdose

    MedlinePlus

    ... class of drugs that includes morphine and other narcotics. Use of prescription opioids for nonmedical reasons is ... tracing) Intravenous fluids (given through a vein) Laxative Narcotic-counteracting drug (antagonist), approximately every 30 minutes Tube ...

  7. What Are Narcotic Drugs?

    ERIC Educational Resources Information Center

    Todays Educ, 1969

    1969-01-01

    Part of "Students and Drug Abuse, prepared by the Public Information Branch and Center for Studies of Narcotic and Drug Abuse, National Institute of Mental Health, in cooperation with the staff of Today's Education.

  8. The Drug Education Gap

    ERIC Educational Resources Information Center

    Reynolds, John C., Jr.

    1976-01-01

    Examines the problems of alcoholism, smoking and drug addiction and their influence on students. Suggests that intermediate and secondary schools can assist in alcohol and tobacco (the two legal drugs) programs through improved educational methods. (Author/RK)

  9. Therapeutic drug levels

    MedlinePlus

    ... medlineplus.gov/ency/article/003430.htm Therapeutic drug levels To use the sharing features on this page, please enable JavaScript. Therapeutic drug levels are lab tests to look for the presence ...

  10. Alcoholism, Alcohol, and Drugs

    ERIC Educational Resources Information Center

    Rubin, Emanuel; Lieber, Charles S.

    1971-01-01

    Describes research on synergistic effects of alcohol and other drugs, particularly barbiturates. Proposes biochemical mechanisms to explain alcoholics' tolerance of other drugs when sober, and increased sensitivity when drunk. (AL)

  11. Drug discovery in academia.

    PubMed

    Shamas-Din, Aisha; Schimmer, Aaron D

    2015-08-01

    Participation of academic centers in aspects of drug discovery and development beyond target identification and clinical trials is rapidly increasing. Yet many academic drug discovery projects continue to stall at the level of chemical probes, and they infrequently progress to drugs suitable for clinical trials. This gap poses a major hurdle for academic groups engaged in drug discovery. A number of approaches have been pursued to overcome this gap, including stopping at the production of high-quality chemical probes, establishing the resources in-house to advance select projects toward clinical trials, partnering with not-for-profit groups to bring the necessary resources and expertise to develop probes into drugs, and drug repurposing, whereby known drugs are advanced into clinical trials for new indications. In this review, we consider the role of academia in anticancer drug discovery and development, as well as the strategies used by academic groups to overcome barriers in this process.

  12. Animal Drug Safety FAQs

    MedlinePlus

    ... the top How do you determine if a veterinary drug is safe to market? As mandated by the ... to the top How does CVM remove unsafe veterinary drugs from the market? See Withdrawal of New Animal ...

  13. Drug Interaction and Pharmacist

    PubMed Central

    Ansari, JA

    2010-01-01

    The topic of drug–drug interactions has received a great deal of recent attention from the regulatory, scientific, and health care communities worldwide. Nonsteroidal anti-inflammatory drugs, antibiotics and, in particular, rifampin are common precipitant drugs prescribed in primary care practice. Drugs with a narrow therapeutic range or low therapeutic index are more likely to be the objects for serious drug interactions. Object drugs in common use include warfarin, fluoroquinolones, antiepileptic drugs, oral contraceptives, cisapride, and 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. The pharmacist, along with the prescriber has a duty to ensure that patients are aware of the risk of side effects and a suitable course of action should they occur. With their detailed knowledge of medicine, pharmacists have the ability to relate unexpected symptoms experienced by patients to possible adverse effects of their drug therapy. PMID:21042495

  14. Prescription Drug Abuse

    MedlinePlus

    ... what the doctor prescribed, it is called prescription drug abuse. It could be Taking a medicine that ... purpose, such as getting high Abusing some prescription drugs can lead to addiction. These include narcotic painkillers, ...

  15. Treating Prescription Drug Addiction

    MedlinePlus

    ... Trends and Alerts Alcohol Club Drugs Cocaine Hallucinogens Heroin Inhalants Marijuana MDMA (Ecstasy/Molly) Methamphetamine Opioids Prescription ... View all ​Research Reports Opioids: The Prescription Drug & Heroin Overdose Epidemic (HHS website) NIDA Home Site Map ...

  16. 40 CFR 180.439 - Thifensulfuron methyl; tolerances for residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... residues of thifensulfuron methyl, including its metabolites and degradates, in or on the commodities... established for residues of thifensulfuron methyl, including its metabolites and degradates, in or on...

  17. 40 CFR 180.239 - Phosphamidon; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances... residues of the insecticide phosphamidon (2-chloro-2-diethylcarbamoyl-1-methylvinyl dimethyl...

  18. Flexibility of active-site gorge aromatic residues and non-gorge aromatic residues in acetylcholinesterase

    SciTech Connect

    Ghattyvenkatakrishna, Pavan K; Uberbacher, Edward C

    2013-01-01

    The presence of an unusually large number of aromatic residues in the active site gorge of acetylcholinesterase has been a topic of great interest. Flexibility of these residues has been suspected to be a key player in controlling ligand traversal in the gorge. This raises the question of whether the over representation of aromatic residues in the gorge implies higher than normal flexibility of those residues. The current study suggests that it does not. Large changes in the hydrophobic cross sectional area due to dihedral oscillations are probably the reason behind their presence in the gorge.

  19. The relationship between blood and muscle samples to monitor for residues of the antibiotic enrofloxacin in chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Use of antibiotics in food animals has generated concern as the presence of these residues in food may contribute to increased microbial resistance in humans. Fluoroquinolone antibiotics are thus now no longer allowed by the U.S. Food and Drug Administration for use in poultry and monitoring of the...

  20. Benzimidazole Carbamate Residues in Milk: Detection by SPR Biosensor; using a Modified QuEChERS Method for Extraction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A surface plasmon resonance (SPR) biosensor screening assay was developed and validated to detect 11 benzimidazole carbamate (BZT) veterinary drug residues in milk. The polyclonal antibody used was raised in sheep against a methyl 5 (6)-[(carboxypentyl)-thio]-2-benzimidazole carbamate protein conjug...

  1. Black Youths and Illegal Drugs.

    ERIC Educational Resources Information Center

    Joseph, Janice; Pearson, Patricia G.

    2002-01-01

    Examines the effect of drugs on black youths, discussing different types of drug involvement, reasons for drug involvement, extent and nature of involvement, drugs and crime, drugs and health issues, drug control strategies, and prevention. Policy implications include prioritizing drug prevention among black youths, providing alternatives to drug…

  2. Contemporary drugs of abuse.

    PubMed

    Giannini, A J; Price, W A; Giannini, M C

    1986-03-01

    The physician needs to know the signs, symptoms and recommended treatments of drug overdoses. Overdose of hallucinogens usually does not require drug therapy. Overdose of amphetamines ("uppers") may be complicated by the presence of PCP, a dissociative substance. It is important for the physician to be familiar with the street terminology for contemporary drugs of abuse and to be aware of how users obtain these drugs.

  3. Sustainable System for Residual Hazards Management

    SciTech Connect

    Kevin M. Kostelnik; James H. Clarke; Jerry L. Harbour

    2004-06-01

    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 longterm 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 externalintrusion 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 longterm success of the prescribed system. In fact

  4. Polypharmacology in a single drug: multitarget drugs.

    PubMed

    Bolognesi, M L

    2013-01-01

    Polypharmacology offers a model for the way drug discovery must evolve to develop therapies most suited to treating currently incurable diseases. It is driven by a worldwide demand for safer, more effective, and affordable medicines against the most complex diseases, and by the failures of modern drug discovery to provide these. Polypharmacology can involve combinations and/or multitarget drugs (MTD). Although not mutually exclusive, my premise is that MTDs have inherent advantages over combinations. This review article focuses on MTDs from a medicinal chemistry perspective. I will explore their use in current clinical practice, their likely application in the future, and the challenges to be overcome to achieve this goal.

  5. Drug Enforcement Administration.

    ERIC Educational Resources Information Center

    Department of Justice, Washington, DC.

    This fact sheet contains information relating to drug abuse and abusers; drug traffic legislation; law enforcement; and descriptions of commonly used narcotics, stimulants, depressants, and hallucinogens. Also included is a short but explicit listing of audiovisual aids, an annotated bibliography, and drug identification pictures. The booklet…

  6. Educating against Drug Abuse.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    This book is a compilation of drug education and drug abuse prevention materials collected by United Nations Educational, Scientific and Cultural Organization (UNESCO) along with example of activities carried out by various countries. It opens with four introductory papers by separate authors: (1) "Prevention of Drug Dependence: A Utopian Dream?"…

  7. Other Drugs of Abuse

    MedlinePlus

    ... can make you pass out. It's called a "date rape" drug because someone can secretly put it in your ... you without your permission. Rohypnol (roofies) is a date rape pill and can ... about these drugs . Bath Salts are drugs made with chemicals like ...

  8. Strategies against Drugs.

    ERIC Educational Resources Information Center

    Metzler, Birgit

    1996-01-01

    The main private organization in Germany dedicated to combatting drug addition--the DHS and the Federal Health Information Agency (BzGA) jointly estimate the number of persons addicted to "illegal" drugs in Germany at around 200,000. Yet, people may grow up immune to drug addiction if they acquire a stable basis for self-confidence and…

  9. Keeping Youth Drug Free.

    ERIC Educational Resources Information Center

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Prevention.

    This guide is designed to help caregivers prevent children from getting involved in drugs. It details six key prevention principles, including actions caregivers can take that can help their child make healthy choices. Each section includes language to use with children, activities to do, information about drugs, statistics about youth drug use,…

  10. Drugs and the Coach.

    ERIC Educational Resources Information Center

    Clarke, Kenneth S., Ed.

    This volume is based on the premise that professional preparation for coaching should include viable experiences in drug education, with particular reference to coping with drug-related problems. The first section provides general information on the purposes and effects of drugs, controls, and concepts of doping. The second section deals with four…

  11. Drugs of Abuse.

    ERIC Educational Resources Information Center

    Joseph, Donald E., Ed.

    This Drug Enforcement Administration publication delivers clear, scientific information about drugs in a factual, straightforward way, combined with precise photographs shot to scale. The publication is intended to serve as an A to Z guide for drug history, effects, and identification information. Chapters are included on the Controlled Substances…

  12. Pesticide residues in birds and mammals

    USGS Publications Warehouse

    Stickel, L.F.; Edwards, C.A.

    1973-01-01

    SUMMARY: Residues of organochlorine pesticides and their breakdown products are present in the tissues of essentially all wild birds throughout the world. These chemicals accumulate in fat from a relatively small environmental exposure. DDE and dieldrin are most prevalent. Others, such as heptachlor epoxide, chlordane, endrin, and benzene hexachloride also occur, the quantities and kinds generally reflecting local or regional use. Accumulation may be sufficient to kill animals following applications for pest control. This has occurred in several large-scale programmes in the United States. Mortality has also resulted from unintentional leakage of chemical from commercial establishments. Residues may persist in the environment for many years, exposing successive generations of animals. In general, birds that eat other birds, or fish, have higher residues than those that eat seeds and vegetation. The kinetic processes of absorption, metabolism, storage, and output differ according to both kind of chemical and species of animal. When exposure is low and continuous, a balance between intake and excretion may be achieved. Residues reach a balance at an approximate animal body equilibrium or plateau; the storage is generally proportional to dose. Experiments with chickens show that dieldrin and heptachlor epoxide have the greatest propensity for storage, endrin next, then DDT, then lindane. The storage of DDT was complicated by its metabolism to DDE and DDD, but other studies show that DDE has a much greater propensity for storage than either DDD or DDT. Methoxychlor has little cumulative capacity in birds. Residues in eggs reflect and parallel those in the parent bird during accumulation, equilibrium, and decline when dosage is discontinued. Residues with the greatest propensity for storage are also lost most slowly. Rate of loss of residues can be modified by dietary components and is speeded by weight loss of the animal. Under sublethal conditions of continuous

  13. Pesticide residues in oranges from Valencia (Spain).

    PubMed

    Fernández, M; Picó, Y; Mañes, J

    2001-07-01

    One hundred and fifty citrus samples from an agricultural co-operative of the Valencian Community (Spain) were analysed for pre- and post-harvest pesticide residues using high performance liquid chromatography and gas chromatography. Among the residues from post-harvest treatments, imazalil was detected in 112 (74.7%) samples at a mean level of 1.2 mg/kg, thiabendazole in 21 (14.0%) samples at a mean level of 0.47 mg/kg and carbendazim in 5 (3.3%) samples at a mean level of 1.05 mg/kg. Among the residues from pre-harvest treatment, dicofol was detected in 28 (18.7%) samples at a mean level of .28 mg/kg chlorpyriphos in 19 (12.7% samples at a mean level of 0.16 mg/kg and endosulfan in 11 (7.3%) at a mean level of 0.27 mg/kg. Most of the samples contained residues of various pesticides and six samples (4.0%) exceeded the European Union Maximum Residue Limit (MRL). The pesticides that surpassed the MRLs were chlorpyriphos in five samples and dicofol in one.

  14. Analytical electron microscopy of LDEF impactor residues

    NASA Technical Reports Server (NTRS)

    Bernhard, Ronald P.; Barrett, Ruth A.; Zolensky, Michael E.

    1995-01-01

    The LDEF contained 57 individual experiment trays or tray portions specifically designed to characterize critical aspects of meteoroid and debris environment in low-Earth orbit (LEO). However, it was realized from the beginning that the most efficient use of the satellite would be to characterize impact features from the entire surface of the LDEF. With this in mind particular interest has focused on common materials facing in all 26 LDEF facing directions; among the most important of these materials has been the tray clamps. Therefore, in an effort to better understand the nature and flux of particulates in LEO, and their effects on spacecraft hardware, we are analyzing residues found in impact features on LDEF tray clamp surfaces. This paper summarizes all data from 79 clamps located on Bay A & B of the LDEF. We also describe current efforts to characterize impactor residues recovered from the impact craters, and we have found that a low, but significant, fraction of these residues have survived in a largely unmelted state. These residues can be characterized sufficiently to permit resolution of the impactor origin. We have concentrated on the residue from chondritic interplanetary dust particles (micrometeoroids), as these represent the harshest test of our analytical capabilities.

  15. Mobility of organic carbon from incineration residues

    SciTech Connect

    Ecke, Holger Svensson, Malin

    2008-07-01

    Dissolved organic carbon (DOC) may affect the transport of pollutants from incineration residues when landfilled or used in geotechnical construction. The leaching of dissolved organic carbon (DOC) from municipal solid waste incineration (MSWI) bottom ash and air pollution control residue (APC) from the incineration of waste wood was investigated. Factors affecting the mobility of DOC were studied in a reduced 2{sup 6-1} experimental design. Controlled factors were treatment with ultrasonic radiation, full carbonation (addition of CO{sub 2} until the pH was stable for 2.5 h), liquid-to-solid (L/S) ratio, pH, leaching temperature and time. Full carbonation, pH and the L/S ratio were the main factors controlling the mobility of DOC in the bottom ash. Approximately 60 weight-% of the total organic carbon (TOC) in the bottom ash was available for leaching in aqueous solutions. The L/S ratio and pH mainly controlled the mobilization of DOC from the APC residue. About 93 weight-% of TOC in the APC residue was, however, not mobilized at all, which might be due to a high content of elemental carbon. Using the European standard EN 13 137 for determination of total organic carbon (TOC) in MSWI residues is inappropriate. The results might be biased due to elemental carbon. It is recommended to develop a TOC method distinguishing between organic and elemental carbon.

  16. Disposal of Rocky Flats residues as waste

    SciTech Connect

    Dustin, D.F.; Sendelweck, V.S.; Rivera, M.A.

    1993-03-01

    Work is underway at the Rocky Flats Plant to evaluate alternatives for the removal of a large inventory of plutonium-contaminated residues from the plant. One alternative under consideration is to package the residues as transuranic wastes for ultimate shipment to the Waste Isolation Pilot Plant. Current waste acceptance criteria and transportation regulations require that approximately 1000 cubic yards of residues be repackaged to produce over 20,000 cubic yards of WIPP certified waste. The major regulatory drivers leading to this increase in waste volume are the fissile gram equivalent, surface radiation dose rate, and thermal power limits. In the interest of waste minimization, analyses have been conducted to determine, for each residue type, the controlling criterion leading to the volume increase, the impact of relaxing that criterion on subsequent waste volume, and the means by which rules changes may be implemented. The results of this study have identified the most appropriate changes to be proposed in regulatory requirements in order to minimize the costs of disposing of Rocky Flats residues as transuranic wastes.

  17. Disposal of Rocky Flats residues as waste

    SciTech Connect

    Dustin, D.F.; Sendelweck, V.S. . Rocky Flats Plant); Rivera, M.A. )

    1993-01-01

    Work is underway at the Rocky Flats Plant to evaluate alternatives for the removal of a large inventory of plutonium-contaminated residues from the plant. One alternative under consideration is to package the residues as transuranic wastes for ultimate shipment to the Waste Isolation Pilot Plant. Current waste acceptance criteria and transportation regulations require that approximately 1000 cubic yards of residues be repackaged to produce over 20,000 cubic yards of WIPP certified waste. The major regulatory drivers leading to this increase in waste volume are the fissile gram equivalent, surface radiation dose rate, and thermal power limits. In the interest of waste minimization, analyses have been conducted to determine, for each residue type, the controlling criterion leading to the volume increase, the impact of relaxing that criterion on subsequent waste volume, and the means by which rules changes may be implemented. The results of this study have identified the most appropriate changes to be proposed in regulatory requirements in order to minimize the costs of disposing of Rocky Flats residues as transuranic wastes.

  18. [Cumulative exposure to pesticide residues in food].

    PubMed

    Kostka, Grazyna; Urbanek-Olejnik, Katarzyna; Liszewska, Monika

    2011-01-01

    The results of food monitoring studies indicate that humans are constantly exposed to residues ofplant protection products (pesticides) in marketed food products. Hence, assessment of the risk to consumers associated with the consumption of products containing residues of the active substances of pesticides is a key stage in both the registration of pesticides and official control of foodstuffs. However there are frequent cases of exposure not only to individual active substances but also to mixtures of pesticide residues. These levels are usually low, below of effective action, and interaction such as synergism orpotentiation is not expected to occur At the same time, literature data indicate that for mixtures sharing a common MOA (Mode of Action/Mechanism of Action), the probability of additive effects is high, even after adjusting for the low levels of the mixed pesticide residues present. Accordingly, health risk assessment for consumers exposed to such mixtures (cumulative/aggregate risk) has become an issue of topical importance. EU-level initiatives regarding the development of appropriate methodology for the estimation of cumulative/aggregate risk have brought about considerable progress in this area. The article discusses various aspects of estimation of cumulative risk for consumers associated with exposure to mixtures of pesticide residues in food.

  19. The magnitude of the sulfa residue problem.

    PubMed

    Van Houweling, C D

    1981-03-01

    Expenditures and losses associated with the so-called sulfa residue problem have totaled about $5 million over the past 6 years. This amount was calculated by recording actual costs when available and by reasonable estimates where actual expenses or losses were not available. It is not conclusive whether the consumers, who are intended to be the benefactors of this program, have received protection commensurate with the expenditures. The losses to producers may be greater if the sulfa problem causes them to discontinue the use of medicated feeds. The problem is the unusually high occurrence of sulfonamide residues in livers of slaughtered swine. In an effort to reduce or eliminate these violative residues, there has been extensive testing of swine livers by the FSQS of the USDA, and inspection of farms from which the pigs were shipped, by the FDA, the Extension Service, and the APHIS. Producers whose pigs are found with violative levels of residue are prohibited from selling more pigs until it has been determined that swine from that farm do not contain violative residues. This restriction can result in serious financial losses to producers.

  20. Treatment of vacuum residues in hydroconversion conditions

    NASA Astrophysics Data System (ADS)

    León, A. Y.; Mendoza, D. L.; Espinosa, J. O.; Laverde, D.

    2016-02-01

    In this paper the use of a liquid homogeneous catalyst has been studied in reactivity vacuum residues by hydroconversion under different conditions. To cover a wide range of compositions, six (6) vacuum residues were selected from crude mixtures. Hydroconversion test were performed in batch reactor with hydrogen atmosphere at about 2000psi in a temperature range between 430 and 480°C. The results allowed to establish that the reactivity hydroconversion conditions about coke formation is higher in vacuum residues with higher content of resins and asphaltenes. The reaction conditions promote distillate formation, however, with increasing stringency conditions, the distillate yield decreases due to distillate transformation into temperature range 430 and 460°C compared to the tests performed without catalyst demonstrating that the use of homogeneous catalyst is an alternative to treating vacuum residues and results are satisfactory in the conversion processes. Finally, predictive expressions have been developed in the formation of products depending on the conditions of temperature and physicochemical properties of processed vacuum residue.

  1. [Migrants from disposable gloves and residual acrylonitrile].

    PubMed

    Wakui, C; Kawamura, Y; Maitani, T

    2001-10-01

    Disposable gloves made from polyvinyl chloride with and without di(2-ethylhexyl) phthalate (PVC-DEHP, PVC-NP), polyethylene (PE), natural rubber (NR) and nitrile-butadiene rubber (NBR) were investigated with respect to evaporation residue, migrated metals, migrants and residual acrylonitrile. The evaporation residue found in n-heptane was 870-1,300 ppm from PVC-DEHP and PVC-NP, which was due to the plasticizers. Most of the PE gloves had low evaporation residue levels and migrants, except for the glove designated as antibacterial, which released copper and zinc into 4% acetic acid. For the NR and NBR gloves, the evaporation residue found in 4% acetic acid was 29-180 ppm. They also released over 10 ppm of calcium and 6 ppm of zinc into 4% acetic acid, and 1.68-8.37 ppm of zinc di-ethyldithiocarbamate and zinc di-n-butyldithiocarbamate used as vulcanization accelerators into n-heptane. The acrylonitrile content was 0.40-0.94 ppm in NBR gloves. PMID:11775358

  2. Drug companies, UNAIDS make drugs available.

    PubMed

    1998-01-01

    The United Nations AIDS (UNAIDS) initiative is working with several drug companies and four countries on a pilot program to build a health infrastructure that provides affordable drugs to insure that combination therapies are used appropriately. The countries involved in the program are Uganda, Chile, Vietnam and Cote d'Ivoire, and the drug companies are Glaxo Wellcome, Hoffmann-La Roche, and Virco NV. Each country agreed to form national HIV/AIDS drug advisory boards, and non-profit companies will act as clearinghouses. Financing will come from the pharmaceutical companies, local health ministries, and a $1 million grant from UNAIDS. The program will be evaluated in terms of improvements to overall health care delivery, number of people treated, the impact on emergency care, and the rate of illness and death.

  3. Drug Rash (Unclassified Drug Eruption) in Adults

    MedlinePlus

    ... microscope by a specially trained physician (dermatopathologist). In addition, your doctor may want to perform blood work to look for signs of an allergic reaction. The best treatment for a drug rash is ...

  4. Unrealized potential and residual consequences of electronic prescribing on pharmacy workflow in the outpatient pharmacy

    PubMed Central

    Nanji, Karen C; Rothschild, Jeffrey M; Boehne, Jennifer J; Keohane, Carol A; Ash, Joan S; Poon, Eric G

    2014-01-01

    Introduction Electronic prescribing systems have often been promoted as a tool for reducing medication errors and adverse drug events. Recent evidence has revealed that adoption of electronic prescribing systems can lead to unintended consequences such as the introduction of new errors. The purpose of this study is to identify and characterize the unrealized potential and residual consequences of electronic prescribing on pharmacy workflow in an outpatient pharmacy. Methods A multidisciplinary team conducted direct observations of workflow in an independent pharmacy and semi-structured interviews with pharmacy staff members about their perceptions of the unrealized potential and residual consequences of electronic prescribing systems. We used qualitative methods to iteratively analyze text data using a grounded theory approach, and derive a list of major themes and subthemes related to the unrealized potential and residual consequences of electronic prescribing. Results We identified the following five themes: Communication, workflow disruption, cost, technology, and opportunity for new errors. These contained 26 unique subthemes representing different facets of our observations and the pharmacy staff's perceptions of the unrealized potential and residual consequences of electronic prescribing. Discussion We offer targeted solutions to improve electronic prescribing systems by addressing the unrealized potential and residual consequences that we identified. These recommendations may be applied not only to improve staff perceptions of electronic prescribing systems but also to improve the design and/or selection of these systems in order to optimize communication and workflow within pharmacies while minimizing both cost and the potential for the introduction of new errors. PMID:24154836

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

    NASA Astrophysics Data System (ADS)

    Qi, Jian-Xun; Jiang, Fan

    2011-05-01

    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.

  6. Residual concentrations of the flukicidal compound triclabendazole in dairy cows' milk and cheese.

    PubMed

    Imperiale, F; Ortiz, P; Cabrera, M; Farias, C; Sallovitz, J M; Iezzi, S; Pérez, J; Alvarez, L; Lanusse, C

    2011-04-01

    Triclabendazole (TCBZ) is a flukicidal halogenated benzimidazole compound extensively used in veterinary medicine. Liver fluke control in lactating dairy cattle is difficult because treatment should be implemented only during the dry period to avoid milk residues. However, control in endemic areas is usually implemented as regular treatments three to four times a year, even during the lactating period. Thus, information on TCBZ milk excretion and the risk of the presence of drug residues in fluid milk and milk-derivate products is essential. The experimental aims were to evaluate the comparative disposition kinetics of TCBZ and its sulpho-metabolites in plasma and milk in lactating dairy cattle after the oral administration (12 mg kg(-1)) of TCBZ and to assess the pattern of residues in cheese made with milk from treated dairy cows. Both TCBZ sulphoxide and sulphone metabolites but not TCBZ were detected in milk (up to 36 and 144 h, respectively) and plasma (up to 144 h) after oral administration of TCBZ. Residual concentrations of TCBZ sulpho-metabolites were found in cheese made with milk from treated animals. The total average residual concentration in fresh cheese was 13.0-fold higher than that obtained in milk used for its elaboration. The high concentrations of TCBZ sulpho-metabolites recovered in fresh cheese should be seriously considered before milk from treated cows is used for making dairy products.

  7. Drug abuse and addiction.

    PubMed

    Nessa, A; Latif, S A; Siddiqui, N I; Hussain, M A; Hossain, M A

    2008-07-01

    Among the social and medical ills of the twentieth century, substance abuse ranks as on one of the most devastating and costly. The drug problem today is a major global concern including Bangladesh. Almost all addictive drugs over stimulate the reward system of the brain, flooding it with the neurotransmitter dopamine. That produces euphoria and that heightened pleasure can be so compelling that the brain wants that feeling back again and again. However repetitive exposure induces widespread adaptive changes in the brain. As a consequence drug use may become compulsive. An estimated 4.7% of the global population aged 15 to 64 or 184 million people, consume illicit drug annually. Heroin use alone is responsible for the epidemic number of new cases of HIV/AIDS, Hepatitis and drug addicted infant born each year. Department of narcotic control (DNC) in Bangladesh reported in June 2008 that about 5 million drug addicts in the country & addicts spend at least 17 (Seventeen) billion on drugs per year. Among these drug addicts, 91% are young and adolescents population. Heroin is the most widely abused drugs in Bangladesh. For geographical reason like India, Pakistan and Myanmar; Bangladesh is also an important transit root for internationally trafficking of illicit drug. Drug abuse is responsible for decreased job productivity and attendance increased health care costs, and escalations of domestic violence and violent crimes. Drug addiction is a preventable disease. Through scientific advances we now know much more about how exactly drugs work in the brain, and we also know that drug addiction can be successfully treated to help people stop abusing drugs and resume their productive lives. Most countries have legislation designed to criminalize some drugs. To decrease the prevalence of this problem in our setting; increase awareness, promoting additional research on abused and addictive drugs, and exact implementation of existing laws are strongly recommended. We should

  8. Drug discovery in jeopardy

    PubMed Central

    Cuatrecasas, Pedro

    2006-01-01

    Despite striking advances in the biomedical sciences, the flow of new drugs has slowed to a trickle, impairing therapeutic advances as well as the commercial success of drug companies. Reduced productivity in the drug industry is caused mainly by corporate policies that discourage innovation. This is compounded by various consequences of mega-mergers, the obsession for blockbuster drugs, the shift of control of research from scientists to marketers, the need for fast sales growth, and the discontinuation of development compounds for nontechnical reasons. Lessons from the past indicate that these problems can be overcome, and herein, new and improved directions for drug discovery are suggested. PMID:17080187

  9. Development and model testing of antemortem screening methodology to predict required drug withholds in heifers.

    PubMed

    Jones, Shuna A; Salter, Robert S; Goldsmith, Tim; Quintana, Julio; Rapnicki, Paul; Shuck, Karen; Wells, Jim E; Schneider, Marilyn J; Griffin, Dee

    2014-02-01

    A simple, cow-side test for the presence of drug residues in live animal fluids would provide useful information for tissue drug residue avoidance programs. This work describes adaptation and evaluation of rapid screening tests to detect drug residues in serum and urine. Medicated heifers had urine, serum, and tissue biopsy samples taken while on drug treatment. Samples were tested by rapid methods and high-performance liquid chromatography (HPLC). The adapted microbial inhibition method, kidney inhibition swab test, was useful in detecting sulfadimethoxine in serum, and its response correlated with the prescribed withdrawal time for the drug, 5 to 6 days posttreatment. The lateral flow screening method for flunixin and beta-lactams, adapted for urine, was useful in predicting flunixin in liver detected by HPLC, 96 h posttreatment. The same adapted methods were not useful to detect ceftiofur in serum or urine due to a lack of sensitivity at the levels of interest. These antemortem screening test studies demonstrated that the method selected, and the sampling matrix chosen (urine or serum), will depend on the drug used and should be based on animal treatment history if available. The live animal tests demonstrated the potential for verification that an individual animal is free of drug residues before sale for human consumption.

  10. Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions

    MedlinePlus

    ... Home Current Issue Past Issues Drug Facts Chat Day: NIH Experts Answer Students' Drug Questions Past Issues / ... Drug Abuse during their first Drug Facts Chat Day. Photo courtesy of NIDA The questions poured in… ...

  11. Putative Drugs and Targets for Bipolar Disorder

    PubMed Central

    Zarate, Carlos A.; Manji, Husseini K.

    2009-01-01

    Current pharmacotherapy for bipolar disorder (BPD) is generally unsatisfactory for a large number of patients. Even with adequate modern bipolar pharmacological therapies, many afflicted individuals continue to have persistent mood episode relapses, residual symptoms, functional impairment and psychosocial disability. Creating novel therapeutics for BPD is urgently needed. Promising drug targets and compounds for BPD worthy of further study involve the following systems: purinergic, dynorphin opioid neuropeptide, cholinergic (muscarinic and nicotinic), melatonin and serotonin (5-HT2C receptor), glutamatergic, hypothalamic-pituitary adrenal (HPA) axis have all been implicated. Intracellular pathways and targets worthy of further study include glycogen synthase kinase-3 protein, protein kinase C, arachidonic acid cascade. PMID:18704977

  12. Drug Interactions and Antiretroviral Drug Monitoring

    PubMed Central

    Foy, Matthew; Sperati, C. John; Lucas, Gregory M.

    2014-01-01

    Due to the improved longevity afforded by combination antiretroviral therapy (cART), HIV-infected individuals are developing several non-AIDS related comorbid conditions. Consequently, medical management of the HIV-infected population is increasingly complex, with a growing list of potential drug-drug interactions (DDIs). This article reviews some of the most relevant and emerging potential interactions between antiretroviral medications and other agents. The most common DDIs are those involving protease inhibitors or non-nucleoside reverse transcriptase inhibitors which alter the cytochrome P450 enzyme system and/or drug transporters such as p-glycoprotein. Of note are the new agents for the treatment of chronic hepatitis C virus infection. These new classes of drugs and others drugs which are increasingly used in this patient population represent a significant challenge with regard to achieving the goals of effective HIV suppression and minimization of drug-related toxicities. Awareness of DDIs and a multidisciplinary approach are imperative in reaching these goals. PMID:24950731

  13. Assessment of tetracycline, lead and cadmium residues in frozen chicken vended in Lagos and Ibadan, Nigeria.

    PubMed

    Olusola, Adetunji Victoria; Diana, Belleh Efie; Ayoade, Odetokun Ismail

    2012-09-01

    This study determined the levels of tetracycline and heavy metals (lead and cadmium) levels in frozen chicken. One hundred frozen chicken muscle samples were sourced from major markets in Lagos and Ibadan (fifty samples each). The samples were analyzed using high power liquid chromatography (HPLC) for tetracycline residue determination while atomic absorption spectroscopy (AAS) was used to determine the levels of lead and cadmium residues in the samples. Mean concentrations of tetracycline residue levels in the frozen chicken sampled ranged from 1.1589-1.0463ppm which is higher than the maximum residue limit set by international food safety agencies. Pb contents were higher in chicken muscles sampled from markets in Ibadan (0.0227 +/- 0.0069 microg dL(-2)) than Lagos (0.0207 +/- 0.0082 microg dL(-1)), while Cd levels were 0.0013 microg dL(-1) higher than in the Lagos samples (0.0065 +/- 0.0026 microg dL(-1)). These values were within maximum residue limits. There were no significant differences (p < 0.05) in levels of tetracycline, lead and cadmium levels from the two market locations (Lagos and Ibadan) and parts (wings and thigh muscles). However, significant differences occurred in tetracycline and Pb levels in frozen chicken sourced from Cotonou. Though not significant, tetracycline contents in the thigh muscles of the frozen chicken samples was higher than that of the wings muscles and this was attributed to the site of administration of antibiotic injection and failure to observe the pre-slaughter withdrawal period by the farmers. This study is of public health importance as the presence of these residues above the maximum residue limit in frozen chicken predisposes consumers to drug resistance, allergic reactions and poisoning as a result of toxicity. PMID:24163968

  14. Molecular Determinants Underlying Binding Specificities of the ABL Kinase Inhibitors: Combining Alanine Scanning of Binding Hot Spots with Network Analysis of Residue Interactions and Coevolution

    PubMed Central

    Tse, Amanda; Verkhivker, Gennady M.

    2015-01-01

    Quantifying binding specificity and drug resistance of protein kinase inhibitors is of fundamental importance and remains highly challenging due to complex interplay of structural and thermodynamic factors. In this work, molecular simulations and computational alanine scanning are combined with the network-based approaches to characterize molecular determinants underlying binding specificities of the ABL kinase inhibitors. The proposed theoretical framework unveiled a relationship between ligand binding and inhibitor-mediated changes in the residue interaction networks. By using topological parameters, we have described the organization of the residue interaction networks and networks of coevolving residues in the ABL kinase structures. This analysis has shown that functionally critical regulatory residues can simultaneously embody strong coevolutionary signal and high network centrality with a propensity to be energetic hot spots for drug binding. We have found that selective (Nilotinib) and promiscuous (Bosutinib, Dasatinib) kinase inhibitors can use their energetic hot spots to differentially modulate stability of the residue interaction networks, thus inhibiting or promoting conformational equilibrium between inactive and active states. According to our results, Nilotinib binding may induce a significant network-bridging effect and enhance centrality of the hot spot residues that stabilize structural environment favored by the specific kinase form. In contrast, Bosutinib and Dasatinib can incur modest changes in the residue interaction network in which ligand binding is primarily coupled only with the identity of the gate-keeper residue. These factors may promote structural adaptability of the active kinase states in binding with these promiscuous inhibitors. Our results have related ligand-induced changes in the residue interaction networks with drug resistance effects, showing that network robustness may be compromised by targeted mutations of key mediating

  15. Computational prediction of heme-binding residues by exploiting residue interaction network.

    PubMed

    Liu, Rong; Hu, Jianjun

    2011-01-01

    Computational identification of heme-binding residues is beneficial for predicting and designing novel heme proteins. Here we proposed a novel method for heme-binding residue prediction by exploiting topological properties of these residues in the residue interaction networks derived from three-dimensional structures. Comprehensive analysis showed that key residues located in heme-binding regions are generally associated with the nodes with higher degree, closeness and betweenness, but lower clustering coefficient in the network. HemeNet, a support vector machine (SVM) based predictor, was developed to identify heme-binding residues by combining topological features with existing sequence and structural features. The results showed that incorporation of network-based features significantly improved the prediction performance. We also compared the residue interaction networks of heme proteins before and after heme binding and found that the topological features can well characterize the heme-binding sites of apo structures as well as those of holo structures, which led to reliable performance improvement as we applied HemeNet to predicting the binding residues of proteins in the heme-free state. HemeNet web server is freely accessible at http://mleg.cse.sc.edu/hemeNet/. PMID:21991319

  16. 40 CFR 721.4500 - Isopropylamine distillation residues and ethylamine distillation residues.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Isopropylamine distillation residues and ethylamine distillation residues. 721.4500 Section 721.4500 Protection of Environment... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.4500 Isopropylamine...

  17. 40 CFR 721.4500 - Isopropylamine distillation residues and ethylamine distillation residues.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Isopropylamine distillation residues and ethylamine distillation residues. 721.4500 Section 721.4500 Protection of Environment... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.4500 Isopropylamine...

  18. 40 CFR 721.4500 - Isopropylamine distillation residues and ethylamine distillation residues.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Isopropylamine distillation residues and ethylamine distillation residues. 721.4500 Section 721.4500 Protection of Environment... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.4500 Isopropylamine...

  19. 40 CFR 721.4500 - Isopropylamine distillation residues and ethylamine distillation residues.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Isopropylamine distillation residues and ethylamine distillation residues. 721.4500 Section 721.4500 Protection of Environment... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.4500 Isopropylamine...

  20. 40 CFR 721.4500 - Isopropylamine distillation residues and ethylamine distillation residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Isopropylamine distillation residues and ethylamine distillation residues. 721.4500 Section 721.4500 Protection of Environment... SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.4500 Isopropylamine...

  1. Crop residue and residue management effects on Armadillidium vulgare (Isopoda: Armadillidiidae) populations and soybean stand densities.

    PubMed

    Johnson, W A; Alfaress, S; Whitworth, R J; McCornack, B P

    2012-10-01

    In general, Armadillidium vulgare (Latreille) are considered nonpests of soybean [Glycine max (L.) Merrill], but changes in soil conservation practices have shifted the pest status of this organism from an opportunistic to a perennial, early-season pest in parts of central Kansas. As a result, soybean producers that rotate with corn (Zea mays L.) under conservation tillage practices have resorted to removing excess corn residue by using controlled burns. In a 2-yr field study (2009-2010), we demonstrated that residue removal in burned compared with unburned plots (measured as previous crop residue weights) had minimal impact on numbers of live and dead A. vulgare, soybean seedling emergence, and isopod feeding damage over time. Specifically, removal of residue by burning did not result in higher emergence rates for soybean stands or less feeding damage by A. vulgare. In a separate study, we found that number of live A. vulgare and residue weights had no consistent relationship with seedling emergence or feeding damage. Furthermore, seedling emergence was not impacted by higher numbers ofA. vulgare in unburned plots, indicating that emergence in this study may have been influenced by factors other than A. vulgare densities. These studies demonstrate that removing residue through controlled burning did not impact seedling emergence in presence of A. vulgare and that residue and feeding damage to seedlings did not consistently relate to A. vulgare densities. Other factors that may have influenced a relationship between residue and live isopod numbers, such as variable moisture levels, are discussed. PMID:23156159

  2. 40 CFR 180.519 - Bromide ion and residual bromine; tolerances for residues.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... additives, bromide ion and residual bromine, may be present in water, potable in accordance with the following conditions: (1) The food additives are present as a result of treating water aboard ships with a...) Residual bromine levels are controlled to not exceed 1.0 part per million (ppm) in the final treated...

  3. Use of imiquimod for residual acral melanoma.

    PubMed

    Sue, Gloria R; Hanlon, Allison; Lazova, Rossitza; Narayan, Deepak

    2014-01-01

    Recent reports suggest that topical imiquimod cream is an effective treatment option for certain types of melanomas. No reports exist on the efficacy of using imiquimod cream to treat melanoma located on the plantar surface of the foot. We present two patients with a melanoma of the foot who had residual melanoma following surgical excision with acceptable margins. The patients were then treated with topical imiquimod for 8 weeks after which a repeat biopsy of the affected region showed no evidence of residual melanoma in situ. The use of topical imiquimod cream should be considered in the management of residual melanoma in situ of the plantar surface of the foot. PMID:25188932

  4. Management of municipal solid waste incineration residues.

    PubMed

    Sabbas, T; Polettini, A; Pomi, R; Astrup, T; Hjelmar, O; Mostbauer, P; Cappai, G; Magel, G; Salhofer, S; Speiser, C; Heuss-Assbichler, S; Klein, R; Lechner, P

    2003-01-01

    The management of residues from thermal waste treatment is an integral part of waste management systems. The primary goal of managing incineration residues is to prevent any impact on our health or environment caused by unacceptable particulate, gaseous and/or solute emissions. This paper provides insight into the most important measures for putting this requirement into practice. It also offers an overview of the factors and processes affecting these mitigating measures as well as the short- and long-term behavior of residues from thermal waste treatment under different scenarios. General conditions affecting the emission rate of salts and metals are shown as well as factors relevant to mitigating measures or sources of gaseous emissions. PMID:12623102

  5. Residual Defect Density in Random Disks Deposits

    NASA Astrophysics Data System (ADS)

    Topic, Nikola; Pöschel, Thorsten; Gallas, Jason A. C.

    2015-08-01

    We investigate the residual distribution of structural defects in very tall packings of disks deposited randomly in large channels. By performing simulations involving the sedimentation of up to 50 × 109 particles we find all deposits to consistently show a non-zero residual density of defects obeying a characteristic power-law as a function of the channel width. This remarkable finding corrects the widespread belief that the density of defects should vanish algebraically with growing height. A non-zero residual density of defects implies a type of long-range spatial order in the packing, as opposed to only local ordering. In addition, we find deposits of particles to involve considerably less randomness than generally presumed.

  6. Residual Stress Predictions in Polycrystalline Alumina

    SciTech Connect

    VEDULA,VENKATA R.; GLASS,S. JILL; SAYLOR,DAVID M.; ROHRER,GREGORY S.; CARTER,W. CRAIG; LANGER,STEPHEN A.

    1999-12-13

    Microstructure-level residual stresses arise in polycrystalline ceramics during processing as a result of thermal expansion anisotropy and crystallographic disorientation across the grain boundaries. Depending upon the grain size, the magnitude of these stresses can be sufficiently high to cause spontaneous microcracking during the processing of these materials. They are also likely to affect where cracks initiate and propagate under macroscopic loading. The magnitudes of residual stresses in untextured and textured alumina samples were predicted using object oriented finite (OOF) element analysis and experimentally determined grain orientations. The crystallographic orientations were obtained by electron-backscattered diffraction (EBSD). The residual stresses were lower and the stress distributions were narrower in the textured samples compared to those in the untextured samples. Crack initiation and propagation were also simulated using the Griffith fracture criterion. The grain boundary to surface energy ratios required for computations were estimated using AFM groove measurements.

  7. Monitoring of seasonal vegetables for pesticide residues.

    PubMed

    Kumari, Beena; Madan, V K; Kumar, R; Kathpal, T S

    2002-03-01

    Market samples (60) of six seasonal vegetables were monitored during 1996-1997 to determine the magnitude of pesticidal contamination. The estimation of insecticide residues representing four major chemical groups i.e. organochlorine, organophosphorous, synthetic pyrethroid and carbamate, was done by adopting a multiresidue analytical technique employing GC-ECD and GC-NPD systems with capillary columns. The tested samples showed 100% contamination with low but measurable amounts of residues. Among the four chemical groups, the organophosphates were dominant followed by organochlorines, synthetic pyrethroids and carbamates. About 23% of the samples showed contamination with organophosphorous compounds above their respective MRL values. More extensive studies covering different regions of Haryana state are suggested to get a clear idea of the magnitude of vegetable contamination with pesticide residues.

  8. Longitudinal residual stresses in boron fibers

    NASA Technical Reports Server (NTRS)

    Behrendt, D. R.

    1976-01-01

    A method of measuring the longitudinal residual stress distribution in boron fibers is presented. The residual stresses in commercial CVD boron on tungsten fibers of 102, 142, and 203 microns (4, 5.6, and 8 mil) diameters were determined. Results for the three sizes show a compressive stress at the surface 800 to -1400 MN/sq m 120 to -200 ksi), changing monotonically to a region of tensile stress within the boron. At approximately 25 percent of the original radius, the stress reaches a maximum tensile 600 to 1000 MN/sq m(90 to 150 ksi) and then decreases to compressive near the tungsten boride core. The core itself is under a compressive stress of approximately -1300 MN/sq m (-190 ksi). The effects of surface removal on core residual stress and core-initiated fracture are discussed.

  9. Permethylation Linkage Analysis Techniques for Residual Carbohydrates

    NASA Astrophysics Data System (ADS)

    Price, Neil P. J.

    Permethylation analysis is the classic approach to establishing the position of glycosidic linkages between sugar residues. Typically, the carbohydrate is derivatized to form acid-stable methyl ethers, hydrolyzed, peracetylated, and analyzed by gas chromatography-mass spectrometry. The position of glycosidic linkages in the starting carbohydrate are apparent from the mass spectra as determined by the location of acetyl residues. The completeness of permethylation is dependent upon the choice of base catalyst and is readily confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry mass spectrometry. For the permethylation of β-cyclodextrin, Hakomori dimsyl base is shown to be superior to the NaOH-dimethyl sulfoxide system, and the use of the latter resulted in selective under-methylation of the 3-hydroxy groups. These techniques are highly applicable to residual carbohydrates from biofuel processes.

  10. Initial deactivation of residue hydrometallation catalysts

    SciTech Connect

    Gualda, G.; Kasztelan, S.

    1995-12-31

    A strong deactivation of residue hydrodemetallization catalysts is usually observed in the first days of a run. We report in this work a comparative study of the deactivation of a NiMo/alumina catalyst with a special pore structure so-called {open_quotes}chestnut burr{close_quotes} by coke and metal+coke deposits. The former set of samples were prepared in batch reactor by varying operating conditions and the latter set of samples were prepared in continuous flow reactor in both cases using a Safaniya atmospheric residue. Various methods were employed to characterize the deposits (TEM, XPS, EPMA, Surface area measurements, porosimetry, etc...) including catalytic tests of the used catalyst with various model reactants, it has been found that metal deposits are responsible for the initial deactivation of the residue hydrodametallation catalyst used in this work.

  11. Residual activation of thin accelerator components

    SciTech Connect

    Mokhov, N.V.; Rakhno, E.I.; Rakhno, I.L.; /Fermilab

    2006-05-01

    A method to calculate residual activation of thin accelerator components is presented. A model for residual dose estimation for thick objects made of arbitrary composite materials for arbitrary irradiation and cooling times is employed in this study. A scaling procedure is described to apply the model to thin objects with linear dimensions less than a fraction of a nuclear interaction length. The scaling has been performed for various materials and corresponding factors have been determined for objects of certain shapes (slab, solid and hollow cylinder) which are important from practical standpoint and can serve as models for beam pipes, magnets and collimators. Both contact residual dose and dose attenuation in air outside the objects were considered. A comparison between calculations and measurements performed at the Fermi National Accelerator Laboratory using a 120 GeV proton beam is presented.

  12. Field Test Kit for Gun Residue Detection

    SciTech Connect

    WALKER, PAMELA K.; RODACY, PHILIP J.

    2002-01-01

    One of the major needs of the law enforcement field is a product that quickly, accurately, and inexpensively identifies whether a person has recently fired a gun--even if the suspect has attempted to wash the traces of gunpowder off. The Field Test Kit for Gunshot Residue Identification based on Sandia National Laboratories technology works with a wide variety of handguns and other weaponry using gunpowder. There are several organic chemicals in small arms propellants such as nitrocellulose, nitroglycerine, dinitrotoluene, and nitrites left behind after the firing of a gun that result from the incomplete combustion of the gunpowder. Sandia has developed a colorimetric shooter identification kit for in situ detection of gunshot residue (GSR) from a suspect. The test kit is the first of its kind and is small, inexpensive, and easily transported by individual law enforcement personnel requiring minimal training for effective use. It will provide immediate information identifying gunshot residue.

  13. Residual Defect Density in Random Disks Deposits

    PubMed Central

    Topic, Nikola; Pöschel, Thorsten; Gallas, Jason A. C.

    2015-01-01

    We investigate the residual distribution of structural defects in very tall packings of disks deposited randomly in large channels. By performing simulations involving the sedimentation of up to 50 × 109 particles we find all deposits to consistently show a non-zero residual density of defects obeying a characteristic power-law as a function of the channel width. This remarkable finding corrects the widespread belief that the density of defects should vanish algebraically with growing height. A non-zero residual density of defects implies a type of long-range spatial order in the packing, as opposed to only local ordering. In addition, we find deposits of particles to involve considerably less randomness than generally presumed. PMID:26235809

  14. Residual Stress Analysis in Thick Uranium Films

    SciTech Connect

    Hodge, A M; Foreman, R J; Gallegos, G F

    2004-12-06

    Residual stress analysis was performed on thick, 1.0 to 25 {micro}m, depleted Uranium (DU) films deposited on an Al substrate by magnetron sputtering. Two distinct characterization techniques were used to measure substrate curvature before and after deposition. Stress evaluation was performed using the Benabdi/Roche equation, which is based on beam theory of a bi-layer material. The residual stress evolution was studied as a function of coating thickness and applied negative bias voltage (0-300V). The stresses developed were always compressive; however, increasing the coating thickness and applying a bias voltage presented a trend towards more tensile stresses and thus an overall reduction of residual stresses.

  15. System and method for measuring residual stress

    DOEpatents

    Prime, Michael B.

    2002-01-01

    The present invention is a method and system for determining the residual stress within an elastic object. In the method, an elastic object is cut along a path having a known configuration. The cut creates a portion of the object having a new free surface. The free surface then deforms to a contour which is different from the path. Next, the contour is measured to determine how much deformation has occurred across the new free surface. Points defining the contour are collected in an empirical data set. The portion of the object is then modeled in a computer simulator. The points in the empirical data set are entered into the computer simulator. The computer simulator then calculates the residual stress along the path which caused the points within the object to move to the positions measured in the empirical data set. The calculated residual stress is then presented in a useful format to an analyst.

  16. Management of municipal solid waste incineration residues.

    PubMed

    Sabbas, T; Polettini, A; Pomi, R; Astrup, T; Hjelmar, O; Mostbauer, P; Cappai, G; Magel, G; Salhofer, S; Speiser, C; Heuss-Assbichler, S; Klein, R; Lechner, P

    2003-01-01

    The management of residues from thermal waste treatment is an integral part of waste management systems. The primary goal of managing incineration residues is to prevent any impact on our health or environment caused by unacceptable particulate, gaseous and/or solute emissions. This paper provides insight into the most important measures for putting this requirement into practice. It also offers an overview of the factors and processes affecting these mitigating measures as well as the short- and long-term behavior of residues from thermal waste treatment under different scenarios. General conditions affecting the emission rate of salts and metals are shown as well as factors relevant to mitigating measures or sources of gaseous emissions.

  17. [Determination of residual organic solvents and macroporous resin residues in Akebia saponin D].

    PubMed

    Wang, Qiao-han; Yang, Xiao-lin; Xiao, Wei; Wang, Zhen-zhong; Ding, Gang; Huang, Wen-zhe; Yang, Zhong-lin

    2015-05-01

    According to ICH, Chinese Pharmacopoeia and supplementary requirements on the separation and purification of herbal extract with macroporous adsorption resin by SFDA, hexane, acetidine, ethanol, benzene, methyl-benzene, o-xylene, m-xylene, p-xylene, styrene, diethyl-benzene and divinyl-benzene of residual organic solvents and macroporous resin residues in Akebia saponin D were determined by headspace capillary GC. Eleven residues in Akebia saponin D were completely separated on DB-wax column, with FID detector, high purity nitrogen as the carry gases. The calibration curves were in good linearity (0.999 2-0.999 7). The reproducibility was good (RSD < 10%). The average recoveries were 80.0% -110%. The detection limit of each component was far lower than the limit concentration. The method is simple, reproducible, and can be used to determine the residual organic solvents and macroporous resin residues in Akebia saponin D. PMID:26390656

  18. Genomic Prediction Accounting for Residual Heteroskedasticity

    PubMed Central

    Ou, Zhining; Tempelman, Robert J.; Steibel, Juan P.; Ernst, Catherine W.; Bates, Ronald O.; Bello, Nora M.

    2015-01-01

    Whole-genome prediction (WGP) models that use single-nucleotide polymorphism marker information to predict genetic merit of animals and plants typically assume homogeneous residual variance. However, variability is often heterogeneous across agricultural production systems and may subsequently bias WGP-based inferences. This study extends classical WGP models based on normality, heavy-tailed specifications and variable selection to explicitly account for environmentally-driven residual heteroskedasticity under a hierarchical Bayesian mixed-models framework. WGP models assuming homogeneous or heterogeneous residual variances were fitted to training data generated under simulation scenarios reflecting a gradient of increasing heteroskedasticity. Model fit was based on pseudo-Bayes factors and also on prediction accuracy of genomic breeding values computed on a validation data subset one generation removed from the simulated training dataset. Homogeneous vs. heterogeneous residual variance WGP models were also fitted to two quantitative traits, namely 45-min postmortem carcass temperature and loin muscle pH, recorded in a swine resource population dataset prescreened for high and mild residual heteroskedasticity, respectively. Fit of competing WGP models was compared using pseudo-Bayes factors. Predictive ability, defined as the correlation between predicted and observed phenotypes in validation sets of a five-fold cross-validation was also computed. Heteroskedastic error WGP models showed improved model fit and enhanced prediction accuracy compared to homoskedastic error WGP models although the magnitude of the improvement was small (less than two percentage points net gain in prediction accuracy). Nevertheless, accounting for residual heteroskedasticity did improve accuracy of selection, especially on individuals of extreme genetic merit. PMID:26564950

  19. Residual Pneumoperitoneum Volume and Postlaparoscopic Cholecystectomy Pain

    PubMed Central

    Sabzi Sarvestani, Amene; Zamiri, Mehdi

    2014-01-01

    Background: Gasretention in the peritoneal cavity plays an important role in inducing postoperative pain after laparoscopy, which is inevitably retained in the peritoneal cavity. Objectives: The aim of this study was to detect the relation between the volume of residual gas and severity of shoulder and abdominal pain. Patients and Methods: In this Prospective study 55 women who were referred for laparoscopic cholecystectomy, were evaluated for the effect of residual pneumoperitoneum on postlaparoscopic cholecystectomy pain intensity. The pneumoperitoneum was graded as absent, mild (1-5 mm), moderate (6-10 mm) and severe (> 11 mm). Patients were followed for postoperative abdominal and shoulder pain using visual analogue scale (VAS), postoperative analgesic requirements, presence of nausea and vomiting, time of unassisted ambulation, time of oral intake and time of return of bowel function in the recovery room and at 6, 12 and 24 hours after operation. Results: At the end of the study, 17 patients (30.9%) had no residual pneumoperitoneum after 24 hours; which 23 (41.81%) had mild residual pneumoperitoneum, eight (14.54%) had moderate pneumoperitoneum and seven (12.72%) had severe pneumoperitoneum. Patients with no or mild residual pneumoperitoneum had significantly lower abdominal and shoulder pain scores than whom with moderate to severe pneumoperitoneum (P = 0.00) and need less meperidine requirements (P = 0.00). Patients did not have any significant difference in time of oral intake, return of bowel function, nausea and vomiting percentages. Conclusions: We conclude that volume of residual pneumoperitoneum is a contributing factor in the etiology of postoperative pain after laparoscopic cholecystectomy. PMID:25599023

  20. Genomic Prediction Accounting for Residual Heteroskedasticity.

    PubMed

    Ou, Zhining; Tempelman, Robert J; Steibel, Juan P; Ernst, Catherine W; Bates, Ronald O; Bello, Nora M

    2015-11-12

    Whole-genome prediction (WGP) models that use single-nucleotide polymorphism marker information to predict genetic merit of animals and plants typically assume homogeneous residual variance. However, variability is often heterogeneous across agricultural production systems and may subsequently bias WGP-based inferences. This study extends classical WGP models based on normality, heavy-tailed specifications and variable selection to explicitly account for environmentally-driven residual heteroskedasticity under a hierarchical Bayesian mixed-models framework. WGP models assuming homogeneous or heterogeneous residual variances were fitted to training data generated under simulation scenarios reflecting a gradient of increasing heteroskedasticity. Model fit was based on pseudo-Bayes factors and also on prediction accuracy of genomic breeding values computed on a validation data subset one generation removed from the simulated training dataset. Homogeneous vs. heterogeneous residual variance WGP models were also fitted to two quantitative traits, namely 45-min postmortem carcass temperature and loin muscle pH, recorded in a swine resource population dataset prescreened for high and mild residual heteroskedasticity, respectively. Fit of competing WGP models was compared using pseudo-Bayes factors. Predictive ability, defined as the correlation between predicted and observed phenotypes in validation sets of a five-fold cross-validation was also computed. Heteroskedastic error WGP models showed improved model fit and enhanced prediction accuracy compared to homoskedastic error WGP models although the magnitude of the improvement was small (less than two percentage points net gain in prediction accuracy). Nevertheless, accounting for residual heteroskedasticity did improve accuracy of selection, especially on individuals of extreme genetic merit.