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

Science.gov (United States)

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

2011-11-01

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

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

Directory of Open Access Journals (Sweden)

saeid shafiei

2017-08-01

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

Comparison of different agar diffusion methods for the detection of residues in the kidneys of pigs treated with antimicrobial drugs.

Science.gov (United States)

Korkeala, H; Sorvettula, O; Mäki-Petäys, O; Hirn, J

1983-01-01

Residue analyses of the kidneys of twenty-six pigs treated with various antimicrobial drugs 20 h before slaughter and of eleven untreated pigs were performed. The effects of storage temperature of the kidneys, and of sampling location, on the residue analysis were also studied. No method alone was sufficient for the detection of residues. Oxytetracycline residues could be detected at pH 6, dihydrostreptomycin residues at pH 8, and sulphonamide residues if trimethoprim was present in the medium. Chloramphenicol, penicillin G procaine, tylosin and lincomycin residues were not detectable with the methods used. The concentration of ampicillin decreased during the storage of samples at +4°C. Most methods also yielded zones of inhibition for the frozen kidneys from untreated pigs. It seems necessary to use agar media of two different pH values: the addition of trimethoprim to the medium is also needed. The use of fresh pig kidneys, and samples containing both kidney medulla and kidney cortex, is recommended in residue analysis. Copyright © 1983. Published by Elsevier Ltd.

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

Science.gov (United States)

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

2016-10-15

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

Determination of potassium concentration in salt water for residual beta radioactivity measurements

International Nuclear Information System (INIS)

Suarez-Navarro, J.A.; Pujol, Ll.

2004-01-01

High interferences may arise in the determination of potassium concentration in salt water. Several analytical methods were studied to determine which method provided the most accurate measurements of potassium concentration. This study is relevant for radiation protection because the exact amount of potassium in water samples must be known for determinations of residual beta activity concentration. The fitting algorithm of the calibration curve and estimation of uncertainty in potassium determinations were also studied. The reproducibility of the proposed analytical method was tested by internal and external validation. Furthermore, the residual beta activity concentration of several Spanish seawater and brackish river water samples was determined using the proposed method

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

Science.gov (United States)

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

2005-04-30

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

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

Directory of Open Access Journals (Sweden)

Hsin-Chun Lee

2018-04-01

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

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

NARCIS (Netherlands)

Corré, W.J.; Conijn, J.G.

2016-01-01

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

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

Science.gov (United States)

2010-12-03

...] Draft Guidance for Industry on Residual Solvents in Animal Drug Products; Questions and Answers... Solvents in Animal Drug Products; Questions and Answers.'' The draft questions and answers (Q&A) guidance addresses the United States Pharmacopeia (USP) General Chapter Residual Solvents that applies to both human...

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

Science.gov (United States)

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.

Determination of anthelmintic drug residues in milk using ultra high performance liquid chromatography-tandem mass spectrometry with rapid polarity switching.

Science.gov (United States)

Whelan, Michelle; Kinsella, Brian; Furey, Ambrose; Moloney, Mary; Cantwell, Helen; Lehotay, Steven J; Danaher, Martin

2010-07-02

A new UHPLC-MS/MS (ultra high 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 concentration step to detect most of the analytes at keeper to ensure analytes remain in solution. Using rapid polarity switching in electrospray ionisation, a single injection was capable of detecting both positively and negatively charged ions in a 13 min run time. The method was validated at two levels: the unapproved use level and at the maximum residue level (MRL) according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCalpha) of the method was in the range of 0.14-1.9 and 11-123 microg kg(-1) for drugs validated at unapproved and MRL levels, respectively. The performance of the method was successfully verified for benzimidazoles and levamisole by participating in a proficiency study.

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

Science.gov (United States)

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

2018-04-01

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

Screening of veterinary drug residues in food by LC-MS/MS. Background and challenges.

Science.gov (United States)

Delatour, Thierry; Racault, Lucie; Bessaire, Thomas; Desmarchelier, Aurélien

2018-04-01

Regulatory agencies and government authorities have established maximum residue limits (MRL) in various food matrices of animal origin for supporting governments and food operators in the monitoring of veterinary drug residues in the food chain, and ultimately in the consumer's plate. Today, about 200 veterinary drug residues from several families, mainly with antibiotic, antiparasitic or antiinflammatory activities, are regulated in a variety of food matrices such as milk, meat or egg. This article provides a review of the regulatory framework in milk and muscle including data from Codex Alimentarius, Europe, the U.S.A., Canada and China for about 220 veterinary drugs. The article also provides a comprehensive overview of the challenge for food control, and emphasizes the pivotal role of liquid chromatography-mass spectrometry (LC-MS), either in tandem with quadrupoles (LC-MS/MS) or high resolution MS (LC-HRMS), for ensuring an adequate consumer protection combined with an affordable cost. The capability of a streamlined LC-MS/MS platform for screening 152 veterinary drug residues in a broad range of raw materials and finished products is highlighted in a production line perspective. The rationale for a suite of four methods intended to achieve appropriate performance in terms of scope and sensitivity is presented. Overall, the platform encompasses one stream for the determination of 105 compounds in a run (based on acidic QuEChERS-like), plus two streams for 23 β-lactams (alkaline QuEChERS-like) and 10 tetracyclines (low-temperature partitioning), respectively, and a dedicated stream for 14 aminoglycosides (molecularly-imprinted polymer).

Hazardous drug residue on exterior vial surfaces: evaluation of a commercial manufacturing process.

Science.gov (United States)

Power, Luci A; Sessink, Paul J M; Gesy, Kathy; Charbonneau, Flay

2014-04-01

Hazardous drug residue on the exterior surface of drug vials poses a potential risk for exposure of health care workers involved in handling these products. The purpose of this article is to heighten the awareness of this serious issue and to evaluate a commercial manufacturing process for removing and containing hazardous drug (HD) residue on exterior vial surfaces. Additionally, findings from this study are interpreted, incorporated into the current body of evidence, and discussed by experts in this field. This study includes separate evaluations for the presence or absence of surface drug contamination on the vials of 3 HD products: 5-fluorouracil, cisplatin, and methotrexate. The drug products were packaged in vials using a patented prewashing/decontamination method, application of a polyvinylchloride (PVC) base, and use of clear glass vials. An additional step of encasing the vial in a shrink-wrapped sheath was used for 5-fluorouracil and cisplatin. Of all 5-fluorouracil (110 vials), methotrexate (60 vials), and cisplatin (60 vials) tested, only 2 had detectable amounts of surface residue. One 5-fluorouracil vial was found to have approximately 4 mg of 5-fluorouracil on the surface of the vial. The second contaminated vial was cisplatin, which was discovered to have 131 ng of platinum, equal to 200 ng of cisplatin or 0.2 μL of cisplatin solution, on the vial sheath. Using validated extraction and analytic methods, all but 2 of the 230 tested vials were found to be free of surface drug contamination. Pharmacy leaders need to take an active role in promoting the need for clean HD vials. Manufacturers should be required to provide their clients with data derived from externally validated analytic studies, reporting the level of HD contamination on the exterior of their vial products.

Study on the pelletizing of sulfate residue with magnetite concentrate in grate-kiln system

Directory of Open Access Journals (Sweden)

Shufeng Y.

2010-01-01

Full Text Available The experiment on the feasibility of pelletizing with magnetite concentrate and the wasted sulfate residue was carried out, to research the performance of pellet in grate-kiln system and simulate the grate-kiln pelletizing process in the micro-pellet roasting simulation system in laboratory, and the process experiments on preheating and roasting sections were conducted. The results show that in order to obtain pellet with good performance and the magnetite concentrate should be over 20 in mass percent, the suitable pelletizing time is about 10 min and moisture is around 12.5%. Also, according to the process parameters of drying and preheating sections obtained from experiment, it will be successful to use magnetite concentrate and the wasted sulfate residue for pelletizing, which exploits a new way for the use of sulfate residue.

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

Science.gov (United States)

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

2018-03-28

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

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

Science.gov (United States)

Ferner, Robin E; Aronson, Jeffrey K

2018-01-01

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

Separation of thorium (IV) from lanthanide concentrate (LC) and water leach purification (WLP) residue

International Nuclear Information System (INIS)

AL-Areqi, Wadeeah M.; Majid, Amran Ab.; Sarmani, Sukiman

2014-01-01

Thorium (IV) content in industrial residue produced from rare earth elements production industry is one of the challenges to Malaysian environment. Separation of thorium from the lanthanide concentrate (LC) and Water Leach Purification (WLP) residue from rare earth elements production plant is described. Both materials have been tested by sulphuric acid and alkaline digestions. Th concentrations in LC and WLP were determined to be 1289.7 ± 129 and 1952.9±17.6 ppm respectively. The results of separation show that the recovery of Th separation from rare earth in LC after concentrated sulphuric acid dissolution and reduction of acidity to precipitate Th was found 1.76-1.20% whereas Th recovery from WLP was less than 4% after concentrated acids and alkali digestion processes. Inductively Coupled Plasma-Mass Spectroscopy (ICP-MS) was used to determine Th concentrations in aqueous phase during separation stages. This study indicated that thorium maybe exists in refractory and insoluble form which is difficult to separate by these processes and stays in WLP residue as naturally occurring radioactive material (NORM)

The Effect of Kaffir Lime Leaves Distillation Residue Oleoresin Concentration on Active Paper Packaging Characteristics

Science.gov (United States)

Kawiji; Utami, R.; Ulum, S.; Khasanah, L. U.; Manuhara, G. J.; Atmaka, W.

2018-03-01

Oleoresin of kaffir lime leaves distillation residue still contains some active compounds such as Citronellal, β-Citronellol, and Linalool which potential to incorporated on the active paper packaging. The purposes of this study were to determine the effect of kaffir lime leaves distillation residue oleoresin concentration on the physical characteristics, sensory characteristics, and antimicrobial activity of the active paper packaging incorporated with kaffir lime leaves distillation residue oleoresin and to determine the functional groups of active paper packaging. The concentration of kaffir lime leaves distillation residue oleoresin were varied at 0%, 2%, 4% and 6%. The result showed that the addition of kaffir lime leaves distillation residue oleoresin increased the thickness and moisture content of the paper and decreased the tensile strengths and folding endurances of active paper packaging. The microbial inhibition tends to increase along with the higher oleoresin concentration addition. Aromatic CH group were found at a wavelength of 897.90 cm-1 of on paper packaging with 2% oleoresin indicated as functional aromatic functional group allegedly obtained from the kaffir lime leaves oleoresin.

Residual Complexity Does Impact Organic Chemistry and Drug Discovery: The Case of Rufomyazine and Rufomycin.

Science.gov (United States)

Choules, Mary P; Klein, Larry L; Lankin, David C; McAlpine, James B; Cho, Sang-Hyun; Cheng, Jinhua; Lee, Hanki; Suh, Joo-Won; Jaki, Birgit U; Franzblau, Scott G; Pauli, Guido F

2018-05-24

Residual complexity (RC) involves the impact of subtle but critical structural and biological features on drug lead validation, including unexplained effects related to unidentified impurities. RC commonly plagues drug discovery efforts due to the inherent imperfections of chromatographic separation methods. The new diketopiperazine, rufomyazine (6), and the previously known antibiotic, rufomycin (7), represent a prototypical case of RC that (almost) resulted in the misassignment of biological activity. The case exemplifies that impurities well below the natural abundance of 13 C (1.1%) can be highly relevant and calls for advanced analytical characterization of drug leads with extended molar dynamic ranges of >1:1,000 using qNMR and LC-MS. Isolated from an actinomycete strain, 6 was originally found to be active against Mycobacterium tuberculosis with a minimum inhibitory concentration (MIC) of 2 μg/mL and high selectivity. As a part of lead validation, the dipeptide was synthesized and surprisingly found to be inactive. The initially observed activity was eventually attributed to a very minor contamination (0.24% [m/m]) with a highly active cyclic peptide (MIC ∼ 0.02 μM), subsequently identified as an analogue of 7. This study illustrates the serious implications RC can exert on organic chemistry and drug discovery, and what efforts are vital to improve lead validation and efficiency, especially in NP-related drug discovery programs.

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

Science.gov (United States)

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

2016-09-09

This paper presents a multi-residue analytical method for 210 drugs in pork using ultra-high-performance liquid chromatography-Q-Trap tandem mass spectrometry (UPLC-MS/MS) within 20min via positive ESI in scheduled multi-reaction monitoring (MRM) mode. The 210 drugs, belonging to 21 different chemical classes, included macrolides, sulfonamides, tetracyclines, β-lactams, β-agonists, aminoglycosides, antiviral drugs, glycosides, phenothiazine, protein anabolic hormones, non-steroidal anti-inflammatory drugs (NSAIDs), quinolones, antifungal drugs, corticosteroids, imidazoles, piperidines, piperazidines, insecticides, amides, alkaloids and others. A rapid and simple preparation method was applied to process the animal tissues, including solvent extraction with an acetonitrile/water mixture (80/20, v/v), defatting and clean-up processes. The recoveries ranged from 52% to 130% with relative standard deviations (RSDs)<20% for spiked concentrations of 10, 50 and 250μg/kg. More than 90% of the analytes achieved low limits of quantification (LOQs)<10μg/kg. The decision limit (CCα), detection capability (CCβ) values were in the range of 2-502μg/kg and 4-505μg/kg, respectively. This method is significant for food safety monitoring and controlling veterinary drug use. Copyright © 2016 Elsevier B.V. All rights reserved.

Multi-residue screening of prioritised human pharmaceuticals, illicit drugs and bactericides in sediments and sludge.

Science.gov (United States)

Langford, Katherine H; Reid, Malcolm; Thomas, Kevin V

2011-08-01

A robust multi-residue method was developed for the analysis of a selection of pharmaceutical compounds, illicit drugs and personal care product bactericides in sediments and sludges. Human pharmaceuticals were selected for analysis in Scottish sewage sludge and freshwater sediments based on prescription, physico-chemical and occurrence data. The method was suitable for the analysis of the selected illicit drugs amphetamine, benzoylecgonine, cocaine, and methamphetamine, the pharmaceuticals atenolol, bendroflumethiazide, carbamazepine, citalopram, diclofenac, fluoxetine, ibuprofen, and salbutamol, and the bactericides triclosan and triclocarban in sewage sludge and freshwater sediment. The method provided an overall recovery of between 56 and 128%, RSDs of between 2 and 19% and LODs of between 1 and 50 ng g(-1). Using the methodology the human pharmaceuticals atenolol, carbamazepine and citalopram and the bactericides triclosan and triclocarban were detected in Scottish sewage sludge. The illicit drugs cocaine, its metabolite benzoylecgonine, amphetamine and methamphetamine were not detected in any of the samples analysed. Triclosan and triclocarban were present at the highest concentrations with triclocarban detected in all but one sample and showing a pattern of co-occurrence in both sludge and sediment samples.

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

International Nuclear Information System (INIS)

2016-08-01

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

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

Science.gov (United States)

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.

Protein microarray: sensitive and effective immunodetection for drug residues

Directory of Open Access Journals (Sweden)

Zer Cindy

2010-02-01

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

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.

Science.gov (United States)

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. Copyright © 2016 John Wiley & Sons, Ltd.

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

NARCIS (Netherlands)

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

2002-01-01

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

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

DEFF Research Database (Denmark)

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

2013-01-01

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

Effect of cooking on enrofloxacin residues in chicken tissue.

Science.gov (United States)

Lolo, M; Pedreira, S; Miranda, J M; Vázquez, B I; Franco, C M; Cepeda, A; Fente, C

2006-10-01

The aim of this study was to determine the effect of different cooking processes (microwaving, roasting, boiling, grilling and frying) on naturally incurred enrofloxacin residues in chicken muscle. Enrofloxacin and its metabolite, ciprofloxacin, were analysed using a validated LC-MS method with limits of detection (LOD) and quantification (LOQ), respectively, of 2 and 5 ng g-1 quinolones in muscle samples. The method was shown to be linear over the range 5-500 ng g-1. Mean intra-day relative standard deviation (RSD) at a concentration of 50 ng g-1 (n = 6) was 6%; inter-day RSD was 12%. A recovery study demonstrated that 65-101%, of the drug and metabolite could be recovered from the tissue. The RSD with naturally incurred roasted chicken breast was 9.18% at a concentration of 11 +/- 1.01 ng g-1 (n = 6). In water, enrofloxacin remained stable for 3 h when heated at 100 degrees C. It was concluded that residue data from raw tissue are valid for estimation of consumer exposure to this drug, as well as the ADI calculations because cooking procedures did not affect enrofloxacin residues, which remained stable during heating. However, there was an apparent decrease in quinolone concentration in tissue because some was lost by exudation into the liquid used for cooking. Conversely, for a cooking procedure with water loss, there was an apparent increase in residue concentration.

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

International Nuclear Information System (INIS)

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

2011-01-01

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

Identification and concentration of selected pesticide residues in Ghanaian cocoa beans

International Nuclear Information System (INIS)

Sefakor, Adzo Fialor

2017-07-01

Pest and disease have been the major causes of low cocoa production worldwide and the use of chemicals in the form of pesticides is one of the main ways of mitigating their undesirable outcome. However, inappropriate application of pesticides does not only affect the quality of cocoa bean products and the well being of consumers of such products but can also damage the natural flora and fauna in the environment. Hence the reason why evaluating the concentrations of pesticide residues is necessary in establishing the quality of a cocoa. The goal of this study was therefore to determine the concentrations and distribution of specific pesticide residues in cocoa beans from the six cocoa growing regions of Ghana. Three classes of pesticides were tested for in cocoa beans obtained from seventeen (17) districts in the Brong Ahafo, Eastern, Central, Western North, Ashanti and Western South cocoa growing regions of Ghana. These were the neonicotinoids (Thiamethoxam, Clothianidin, Imidacloprid and Acetamiprid); the synthetic pyrethroids (Cypermethrin, Deltamethrin, Fenvalerate, Lambda Cyhalothrin and Permethrin) and the organophosphorous compound Chlorpyrifos. Pesticide residue analyses were done separately on the whole unshelled beans, the nibs and the shells using a GC/ECD for the synthetic pyrethroids and organophosphorous compound and a QqQ-LC/MS for the neonicotinoids. The results obtained showed that the mean concentrations of the neonicotinoids in all the three matrices ranged from <0.001 to 0.018 mg/kg in the shells, <0.001 to 0.0025 mg/kg in the nibs and <0.001 to 0.005 mg/kg in the whole beans with Imidacloprid being the predominant one. Ashanti Region had the highest concentration of Imidacloprid in all the three matrices whilst Eastern Region recorded the least concentration of Imidacloprid in the shells (0.009 mg/kg) and whole unshelled beans (0.002 mg/kg). In relations to the synthetic pyrethroids tested for, the results obtained indicated that out of the

Urine Creatinine Concentrations in Drug Monitoring Participants and Hospitalized Patients.

Science.gov (United States)

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

2016-10-01

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

Mathematical Model to Predict Skin Concentration after Topical Application of Drugs

Directory of Open Access Journals (Sweden)

Hiroaki Todo

2013-12-01

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

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

Directory of Open Access Journals (Sweden)

Richard Van Vleck Pereira

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-09-14

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

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

International Nuclear Information System (INIS)

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

2016-01-01

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

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

Science.gov (United States)

Hussain, Musaddeq

2015-11-10

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

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

Science.gov (United States)

2012-01-25

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

Serum magnesium concentration in drug-addicted patients.

Science.gov (United States)

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

2007-03-01

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

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

NARCIS (Netherlands)

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

2013-01-01

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

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

Science.gov (United States)

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

2017-11-01

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

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

Directory of Open Access Journals (Sweden)

ZORAN B. TODOROVIĆ

2009-09-01

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

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

International Nuclear Information System (INIS)

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

2017-01-01

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

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

OpenAIRE

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

2018-01-01

Antibiotics have been widely used in the treatment of livestock diseases. However, the emergence of issues related to drug resistance prompted governments to enact a series of laws regulating the use of antibiotics in livestock. Following control of the problem of drug resistant bacteria, public attention has shifted to the recurring incidence of human health and safety issues caused by residual veterinary drugs in livestock products. To guarantee the safety and hygiene of meat, milk, and egg...

Drug residues recovered in feed after various feedlot mixer truck cleanout procedures.

Science.gov (United States)

Van Donkersgoed, Joyce; Sit, Dan; Gibbons, Nicole; Ramogida, Caterina; Hendrick, Steve

2010-01-01

A study was conducted to determine the effectiveness of two methods of equipment cleanout, sequencing or flushing, for reducing drug carryover in feedlot mixer trucks. Feed samples were collected from total mixed rations before and after various feed mixer equipment cleanout procedures. Medicated rations contained either 11 ppm of tylosin or 166 or 331 ppm of chlortetracycline. There were no differences between sequencing and flushing or between flushing with dry barley and flushing with barley silage in the median proportion of drug recovered in the next ration. A larger drug reduction was achieved using flush material at a volume of 10 versus 5% of the mixer capacity and mixing the flush material for 3 versus 4 min. Regardless of the drug or prescription concentrations in the total mixed rations or the equipment cleanout procedure used, concentrations of chlortetracycline and tylosin recovered were very low.

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

International Nuclear Information System (INIS)

Brenes Jimenez, Jose Eduardo

2009-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2003-07-01

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

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

DEFF Research Database (Denmark)

Tran, Thuy; Chakraborty, Anjan; Xi, Xi

2018-01-01

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

Comparison of veterinary drug residue results in animal tissues by ultrahigh-performance liquid chromatography coupled to triple quadrupole ... use of a commercial lipid removal product

Science.gov (United States)

Veterinary drug residues in animal-derived foods must be monitored to ensure food safety, verify proper veterinary practices, enforce legal limits in domestic and imported foods, and other purposes. A common goal in drug residue analysis in foods is to achieve acceptable monitoring results for as m...

The selenazal drug ebselen potently inhibits indoleamine 2,3-dioxygenase by targeting enzyme cysteine residues.

Science.gov (United States)

Terentis, Andrew C; Freewan, Mohammed; Sempértegui Plaza, Tito S; Raftery, Mark J; Stocker, Roland; Thomas, Shane R

2010-01-26

The heme enzyme indoleamine 2,3-dioxygenase (IDO) plays an important immune regulatory role by catalyzing the oxidative degradation of l-tryptophan. Here we show that the selenezal drug ebselen is a potent IDO inhibitor. Exposure of human macrophages to ebselen inhibited IDO activity in a manner independent of changes in protein expression. Ebselen inhibited the activity of recombinant human IDO (rIDO) with an apparent inhibition constant of 94 +/- 17 nM. Optical and resonance Raman spectroscopy showed that ebselen altered the active site heme of rIDO by inducing a transition of the ferric heme iron from the predominantly high- to low-spin form and by lowering the vibrational frequency of the Fe-CO stretch of the CO complex, indicating an opening of the distal heme pocket. Substrate binding studies showed that ebselen enhanced nonproductive l-tryptophan binding, while circular dichroism indicated that the drug reduced the helical content and protein stability of rIDO. Thiol labeling and mass spectrometry revealed that ebselen reacted with multiple cysteine residues of IDO. Removal of cysteine-bound ebselen with dithiothreitol reversed the effects of the drug on the heme environment and significantly restored enzyme activity. These findings indicate that ebselen inhibits IDO activity by reacting with the enzyme's cysteine residues that result in changes to protein conformation and active site heme, leading to an increase in the level of nonproductive substrate binding. This study highlights that modification of cysteine residues is a novel and effective means of inhibiting IDO activity. It also suggests that IDO is under redox control and that the enzyme represents a previously unrecognized in vivo target of ebselen.

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

Science.gov (United States)

Megalopoulos, Fivos A; Ochsenkuehn-Petropoulou, Maria T

2015-01-01

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

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

Science.gov (United States)

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

2016-10-01

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

Distribution of Penicillin G Residues in Culled Dairy Cow Muscles: Implications for Residue Monitoring

Science.gov (United States)

The U.S. Food and Drug Administration sets tolerances for veterinary drug residues in muscle, but does not specify which type of muscle should be analyzed. In order to determine if antibiotic residue levels are dependent on muscle type, 7 culled dairy cows were dosed with Penicillin G (Pen G) from ...

A single acidic residue can guide binding site selection but does not govern QacR cationic-drug affinity.

Directory of Open Access Journals (Sweden)

Kate M Peters

Full Text Available Structures of the multidrug-binding repressor protein QacR with monovalent and bivalent cationic drugs revealed that the carboxylate side-chains of E90 and E120 were proximal to the positively charged nitrogens of the ligands ethidium, malachite green and rhodamine 6G, and therefore may contribute to drug neutralization and binding affinity. Here, we report structural, biochemical and in vivo effects of substituting these glutamate residues. Unexpectedly, substitutions had little impact on ligand affinity or in vivo induction capabilities. Structures of QacR(E90Q and QacR(E120Q with ethidium or malachite green took similar global conformations that differed significantly from all previously described QacR-drug complexes but still prohibited binding to cognate DNA. Strikingly, the QacR(E90Q-rhodamine 6G complex revealed two mutually exclusive rhodamine 6G binding sites. Despite multiple structural changes, all drug binding was essentially isoenergetic. Thus, these data strongly suggest that rather than contributing significantly to ligand binding affinity, the role of acidic residues lining the QacR multidrug-binding pocket is primarily to attract and guide cationic drugs to the "best available" positions within the pocket that elicit QacR induction.

Pre-concentration of pesticide residues in environmental water samples using Silica nanoparticles and identification of residues By GC-MS method

OpenAIRE

Tentu. Nageswara Rao; A. Muralidhar Reddy; SNVS. Murthy; Prathipati Revathi; K. Suneel Kumar

2016-01-01

The silica nanoparticles prepared by stober’s mechanism by reaction of tetraethylorthosilicate (TEOS) with ammonia was tested for their adsorption capacity in the pre-concentration of residues of pesticides in water. The synthesized nanoparticles were characterized by Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM) and X-Ray Diffraction (XRD). The size of the silica nanoparticles were 50 to 250 nm. The solid phase extraction (SPE) cartridges were prepared by filling...

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

OpenAIRE

Heidkamp, William

2016-01-01

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

Residual concentrations of micropollutants in benthic mussels in the coastal areas of Bohai Sea, North China

International Nuclear Information System (INIS)

Liu Wenxin; Chen Jianglin; Lin Xiumei; Fan Yongsheng; Tao Shu

2007-01-01

Studies of heavy metals and organic pollutants in different benthic mussel species from Bohai Sea show that concentrations of Cd in mussels commonly exceed national biological quality standards. In addition, a site located in Laizhou Bay exhibits higher average concentrations of As, Hg and Pb with respect to the other sites. Residual levels of petroleum hydrocarbons at several sites in Liaodong Bay also exceed quality guidelines. Contents and compositional characteristics of DDT and its metabolites in mussels suggest the probability of recent inputs and potential ecological risks to the local benthic environment. - Residual Cd contents of mussels at many sites in Bohai Sea exceed national marine biological quality standard and compositions of DDT metabolites indicate recent inputs and potential risk

Development of an improved high resolution mass spectrometry based multi-residue method for veterinary drugs in various food matrices.

Science.gov (United States)

Kaufmann, A; Butcher, P; Maden, K; Walker, S; Widmer, M

2011-08-26

Multi-residue methods for veterinary drugs or pesticides in food are increasingly often based on ultra performance liquid chromatography (UPLC) coupled to high resolution mass spectrometry (HRMS). Previous available time of flight (TOF) technologies, showing resolutions up to 15,000 full width at half maximum (FWHM), were not sufficiently selective for monitoring low residue concentrations in difficult matrices (e.g. hormones in tissue or antibiotics in honey). The approach proposed in this paper is based on a single stage Orbitrap mass spectrometer operated at 50,000 FWHM. Extracts (liver and kidney) which were produced according to a validated multi-residue method (time of flight detection based) could not be analyzed by Orbitrap because of extensive signal suppression. This required the improvement of established extraction and clean-up procedures. The introduced, more extensive deproteinzation steps and dedicated instrumental settings successfully eliminated these detrimental suppression effects. The reported method, covering more than 100 different veterinary dugs, was validated according to the EU Commission Decision 2002/657/EEC. Validated matrices include muscle, kidney, liver, fish and honey. Significantly better performance parameters (e.g. linearity, reproducibility and detection limits) were obtained when comparing the new method with the older, TOF based method. These improvements are attributed to the higher resolution (50,000 versus 12,000 FWHM) and the superior mass stability of the of the Orbitrap over the previously utilized TOF instrument. Copyright © 2010 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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

2014-06-01

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

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

Science.gov (United States)

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

2015-01-01

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

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

Science.gov (United States)

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

2013-06-01

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

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

Science.gov (United States)

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

2017-01-01

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

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

Science.gov (United States)

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

2017-06-01

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

Estimation of polycyclic aromatic hydrocarbon concentrations in the water column based on tissue residues in mussels and salmon: An equilibrium partitioning approach

International Nuclear Information System (INIS)

Neff, J.M.; Burns, W.A.

1996-01-01

Equilibrium partitioning was used to estimate concentrations of dissolved polycyclic aromatic hydrocarbons (PAHs) in the water column from PAH residues in tissues of mussels and juvenile pink salmon collected from coastal marine waters affected by the Exxon Valdez oil spill. Estimated concentrations were within factors of 2 to 5 for fish and 5 to 10 for mussels of average total dissolved and particulate PAHs measured in concurrent water samples. Temporal trends of estimated and measured water-column PAH concentrations were comparable. Water-column PAH concentrations estimated from residues in tissues of mussels (Mytilus trossulus) were higher than estimates based on residues in tissues of juvenile pink salmon (Oncorhynchus gorbuscha). Possible reasons for this difference include seasonal variations in mussel lipid content, differences in PAH uptake and depuration rates between fish and mussels, differences in how fish and mussels interact with particulate oil, and possible short exposure times for juvenile pink salmon. All of these factors may play a role. In any event, estimates of dissolved PAHs in the water column, based on PAH residues in either fish or mussel tissue, confirm that PAH concentrations generally did not exceed water quality standards for protection of marine life

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

Directory of Open Access Journals (Sweden)

Malcolm J. Reid

2011-12-01

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

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

Science.gov (United States)

Tylutki, Zofia; Polak, Sebastian

2015-03-12

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

Validation of an HPLC-UV method for the determination of ceftriaxone sodium residues on stainless steel surface of pharmaceutical manufacturing equipments.

Science.gov (United States)

Akl, Magda A; Ahmed, Mona A; Ramadan, Ahmed

2011-05-15

In pharmaceutical industry, an important step consists in the removal of possible drug residues from the involved equipments and areas. The cleaning procedures must be validated and methods to determine trace amounts of drugs have, therefore, to be considered with special attention. An HPLC-UV method for the determination of ceftriaxone sodium residues on stainless steel surface was developed and validated in order to control a cleaning procedure. Cotton swabs, moistened with extraction solution (50% water and 50% mobile phase), were used to remove any residues of drugs from stainless steel surfaces, and give recoveries of 91.12, 93.8 and 98.7% for three concentration levels. The precision of the results, reported as the relative standard deviation (RSD), were below 1.5%. The method was validated over a concentration range of 1.15-6.92 μg ml(-1). Low quantities of drug residues were determined by HPLC-UV using a Hypersil ODS 5 μm (250×4.6 mm) at 50 °C with an acetonitrile:water:pH 7:pH 5 (39-55-5.5-0.5) mobile phase at flow rate of 1.5 ml min(-1), an injection volume of 20 μl and were detected at 254 nm. A simple, selective and sensitive HPLC-UV assay for the determination of ceftriaxone sodium residues on stainless steel surfaces was developed, validated and applied. Copyright © 2011 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

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

1991-01-01

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

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

Directory of Open Access Journals (Sweden)

Zuhura I. Kimera

2015-11-01

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

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

Science.gov (United States)

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

2015-11-27

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.

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

NARCIS (Netherlands)

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

2001-01-01

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

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

Science.gov (United States)

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

2016-08-01

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

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

Science.gov (United States)

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

2013-01-01

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

Concentrations and dissipation of difenoconazole and fluxapyroxad residues in apples and soil, determined by ultrahigh-performance liquid chromatography electrospray ionization tandem mass spectrometry.

Science.gov (United States)

He, Min; Jia, Chunhong; Zhao, Ercheng; Chen, Li; Yu, Pingzhong; Jing, Junjie; Zheng, Yongquan

2016-03-01

A new combined difenoconazole and fluxapyroxad fungicide formulation, as an 11.7 % suspension concentrate (SC), has been introduced as part of a resistance management strategy. The dissipation of difenoconazole and fluxapyroxad applied to apples and the residues remaining in the apples were determined. The 11.7 % SC was sprayed onto apple trees and soil in Beijing, Shandong, and Anhui provinces, China, at an application rate of 118 g a.i. ha(-1), then the dissipation of difenoconazole and fluxapyroxad was monitored. The residual difenoconazole and fluxapyroxad concentrations were determined by ultrahigh-performance liquid chromatography tandem mass spectrometry. The difenoconazole half-lives in apples and soil were 6.2-9.5 and 21.0-27.7 days, respectively. The fluxapyroxad half-lives in apples and soil were 9.4-12.6 and 10.3-36.5 days, respectively. Difenoconazole and fluxapyroxad residues in apples and soil after the 11.7 % SC had been sprayed twice and three times, with 10 days between applications, at 78 and 118 g a.i. ha(-1) were measured. Representative apple and soil samples were collected after the last treatment, at preharvest intervals of 14, 21, and 28 days. The difenoconazole residue concentrations in apples and soil were 0.002-0.052 and 0.002-0.298 mg kg(-1), respectively. The fluxapyroxad residue concentrations in apples and soil were 0.002-0.093 and 0.008-1.219 mg kg(-1), respectively. The difenoconazole and fluxapyroxad residue concentrations in apples were lower than the maximum residue limits (0.5 and 0.8 mg kg(-1), respectively). An application rate of 78 g a.i. ha(-1) is therefore recommended to ensure that treated apples can be considered safe for humans to consume.

Thorium, uranium and rare earth elements content in lanthanide concentrate (LC) and water leach purification (WLP) residue of Lynas advanced materials plant (LAMP)

Science.gov (United States)

AL-Areqi, Wadeeah M.; Majid, Amran Ab.; Sarmani, Sukiman

2014-02-01

Lynas Advanced Materials Plant (LAMP) has been licensed to produce the rare earths elements since early 2013 in Malaysia. LAMP processes lanthanide concentrate (LC) to extract rare earth elements and subsequently produce large volumes of water leach purification (WLP) residue containing naturally occurring radioactive material (NORM). This residue has been rising up the environmental issue because it was suspected to accumulate thorium with significant activity concentration and has been classified as radioactive residue. The aim of this study is to determine Th-232, U-238 and rare earth elements in lanthanide concentrate (LC) and water leach purification (WLP) residue collected from LAMP and to evaluate the potential radiological impacts of the WLP residue on the environment. Instrumental Neutron Activation Analysis and γ-spectrometry were used for determination of Th, U and rare earth elements concentrations. The results of this study found that the concentration of Th in LC was 1289.7 ± 129 ppm (5274.9 ± 527.6Bq/kg) whereas the Th and U concentrations in WLP were determined to be 1952.9±17.6 ppm (7987.4 ± 71.9 Bq/kg) and 17.2 ± 2.4 ppm respectively. The concentrations of Th and U in LC and WLP samples determined by γ- spectrometry were 1156 ppm (4728 ± 22 Bq/kg) & 18.8 ppm and 1763.2 ppm (7211.4 Bq/kg) &29.97 ppm respectively. This study showed that thorium concentrations were higher in WLP compare to LC. This study also indicate that WLP residue has high radioactivity of 232Th compared to Malaysian soil natural background (63 - 110 Bq/kg) and come under preview of Act 304 and regulations. In LC, the Ce and Nd concentrations determined by INAA were 13.2 ± 0.6% and 4.7 ± 0.1% respectively whereas the concentrations of La, Ce, Nd and Sm in WLP were 0.36 ± 0.04%, 1.6%, 0.22% and 0.06% respectively. This result showed that some amount of rare earth had not been extracted and remained in the WLP and may be considered to be reextracted.

Thorium, uranium and rare earth elements content in lanthanide concentrate (LC) and water leach purification (WLP) residue of Lynas advanced materials plant (LAMP)

International Nuclear Information System (INIS)

AL-Areqi, Wadeeah M.; Majid, Amran Ab.; Sarmani, Sukiman

2014-01-01

Lynas Advanced Materials Plant (LAMP) has been licensed to produce the rare earths elements since early 2013 in Malaysia. LAMP processes lanthanide concentrate (LC) to extract rare earth elements and subsequently produce large volumes of water leach purification (WLP) residue containing naturally occurring radioactive material (NORM). This residue has been rising up the environmental issue because it was suspected to accumulate thorium with significant activity concentration and has been classified as radioactive residue. The aim of this study is to determine Th-232, U-238 and rare earth elements in lanthanide concentrate (LC) and water leach purification (WLP) residue collected from LAMP and to evaluate the potential radiological impacts of the WLP residue on the environment. Instrumental Neutron Activation Analysis and γ-spectrometry were used for determination of Th, U and rare earth elements concentrations. The results of this study found that the concentration of Th in LC was 1289.7 ± 129 ppm (5274.9 ± 527.6Bq/kg) whereas the Th and U concentrations in WLP were determined to be 1952.9±17.6 ppm (7987.4 ± 71.9 Bq/kg) and 17.2 ± 2.4 ppm respectively. The concentrations of Th and U in LC and WLP samples determined by γ- spectrometry were 1156 ppm (4728 ± 22 Bq/kg) and 18.8 ppm and 1763.2 ppm (7211.4 Bq/kg) and 29.97 ppm respectively. This study showed that thorium concentrations were higher in WLP compare to LC. This study also indicate that WLP residue has high radioactivity of 232 Th compared to Malaysian soil natural background (63 - 110 Bq/kg) and come under preview of Act 304 and regulations. In LC, the Ce and Nd concentrations determined by INAA were 13.2 ± 0.6% and 4.7 ± 0.1% respectively whereas the concentrations of La, Ce, Nd and Sm in WLP were 0.36 ± 0.04%, 1.6%, 0.22% and 0.06% respectively. This result showed that some amount of rare earth had not been extracted and remained in the WLP and may be considered to be reextracted

Thorium, Uranium and Rare Earth Elements content in lanthanide concentrate (LC) and water leach purification (WLP) residue of Lynas Advanced Materials Plant (LAMP)

International Nuclear Information System (INIS)

Al-Areqi, W.M.; Amran Abdul Majid; Sukiman Sarmani

2013-01-01

Full-text: Lynas Advanced Materials Plant (LAMP) has been licensed to produce the rare earths elements since early 2013 in Malaysia. LAMP processes lanthanide concentrate (LC) to extract rare earth elements and subsequently produce large volumes of water leach purification (WLP) residue containing naturally occurring radioactive material (NORM). This residue has been rising up the environmental issue because it was suspected to accumulate thorium with significant activity concentration and has been classified as radioactive residue. The aim of this study is to determine Th-232, U-238 and rare earth elements in lanthanide concentrate (LC) and water leach purification (WLP) residue collected from LAMP and to evaluate the potential radiological impacts of the WLP residue on the environment. Instrumental Neutron Activation Analysis and γ-spectrometry were used for determination of Th, U and rare earth elements concentrations. The results of this study found that the concentration of Th in LC was 1289.7 ± 129 ppm (5274.9 ± 527.6 Bq/ kg) whereas the Th and U concentrations in WLP were determined to be 1952.9 ± 17.6 ppm (7987.4 ± 71.9 Bq/ kg) and 17.2 ± 2.4 ppm respectively. The concentrations of Th and U in LC and WLP samples determined by γ- spectrometry were 1156 ppm (4728 ± 22 Bq/ kg) and 18.8 ppm and 1763.2 ppm (7211.4 Bq/ kg) and 29.97 ppm respectively. This study showed that thorium concentrations were higher in WLP compare to LC. This study also indicate that WLP residue has high radioactivity of 232 Th compared to Malaysian soil natural background (63 - 110 Bq/ kg) and come under preview of Act 304 and regulations. In LC, the Ce and Nd concentrations determined by INAA were 13.2 ± 0.6 % and 4.7 ± 0.1 % respectively whereas the concentrations of La, Ce, Nd and Sm in WLP were 0.36 ± 0.04 %, 1.6 %, 0.22 % and 0.06 % respectively. This result showed that some amount of rare earth had not been extracted and remained in the WLP and may be considered to be re

Thorium, uranium and rare earth elements content in lanthanide concentrate (LC) and water leach purification (WLP) residue of Lynas advanced materials plant (LAMP)

Energy Technology Data Exchange (ETDEWEB)

AL-Areqi, Wadeeah M., E-mail: walareqi@yahoo.com; Majid, Amran Ab., E-mail: walareqi@yahoo.com; Sarmani, Sukiman, E-mail: walareqi@yahoo.com [Nuclear Science Programme, School of Chemical Sciences and Food Technology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi (Malaysia)

2014-02-12

Lynas Advanced Materials Plant (LAMP) has been licensed to produce the rare earths elements since early 2013 in Malaysia. LAMP processes lanthanide concentrate (LC) to extract rare earth elements and subsequently produce large volumes of water leach purification (WLP) residue containing naturally occurring radioactive material (NORM). This residue has been rising up the environmental issue because it was suspected to accumulate thorium with significant activity concentration and has been classified as radioactive residue. The aim of this study is to determine Th-232, U-238 and rare earth elements in lanthanide concentrate (LC) and water leach purification (WLP) residue collected from LAMP and to evaluate the potential radiological impacts of the WLP residue on the environment. Instrumental Neutron Activation Analysis and γ-spectrometry were used for determination of Th, U and rare earth elements concentrations. The results of this study found that the concentration of Th in LC was 1289.7 ± 129 ppm (5274.9 ± 527.6Bq/kg) whereas the Th and U concentrations in WLP were determined to be 1952.9±17.6 ppm (7987.4 ± 71.9 Bq/kg) and 17.2 ± 2.4 ppm respectively. The concentrations of Th and U in LC and WLP samples determined by γ- spectrometry were 1156 ppm (4728 ± 22 Bq/kg) and 18.8 ppm and 1763.2 ppm (7211.4 Bq/kg) and 29.97 ppm respectively. This study showed that thorium concentrations were higher in WLP compare to LC. This study also indicate that WLP residue has high radioactivity of {sup 232}Th compared to Malaysian soil natural background (63 - 110 Bq/kg) and come under preview of Act 304 and regulations. In LC, the Ce and Nd concentrations determined by INAA were 13.2 ± 0.6% and 4.7 ± 0.1% respectively whereas the concentrations of La, Ce, Nd and Sm in WLP were 0.36 ± 0.04%, 1.6%, 0.22% and 0.06% respectively. This result showed that some amount of rare earth had not been extracted and remained in the WLP and may be considered to be reextracted.

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

Directory of Open Access Journals (Sweden)

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

2005-07-01

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

Homology modeling and docking analyses of M. leprae Mur ligases reveals the common binding residues for structure based drug designing to eradicate leprosy.

Science.gov (United States)

Shanmugam, Anusuya; Natarajan, Jeyakumar

2012-06-01

Multi drug resistance capacity for Mycobacterium leprae (MDR-Mle) demands the profound need for developing new anti-leprosy drugs. Since most of the drugs target a single enzyme, mutation in the active site renders the antibiotic ineffective. However, structural and mechanistic information on essential bacterial enzymes in a pathway could lead to the development of antibiotics that targets multiple enzymes. Peptidoglycan is an important component of the cell wall of M. leprae. The biosynthesis of bacterial peptidoglycan represents important targets for the development of new antibacterial drugs. Biosynthesis of peptidoglycan is a multi-step process that involves four key Mur ligase enzymes: MurC (EC:6.3.2.8), MurD (EC:6.3.2.9), MurE (EC:6.3.2.13) and MurF (EC:6.3.2.10). Hence in our work, we modeled the three-dimensional structure of the above Mur ligases using homology modeling method and analyzed its common binding features. The residues playing an important role in the catalytic activity of each of the Mur enzymes were predicted by docking these Mur ligases with their substrates and ATP. The conserved sequence motifs significant for ATP binding were predicted as the probable residues for structure based drug designing. Overall, the study was successful in listing significant and common binding residues of Mur enzymes in peptidoglycan pathway for multi targeted therapy.

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

NARCIS (Netherlands)

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

2005-01-01

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

The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance

Science.gov (United States)

Dingemans, Jozef; Poudyal, Bandita

2018-01-01

ABSTRACT The formation of inherently drug-tolerant biofilms by the opportunistic pathogen Pseudomonas aeruginosa requires the sensor-regulator hybrid SagS, with ΔsagS biofilms being unstructured and exhibiting increased antimicrobial susceptibility. Recent findings indicated SagS to function as a switch to control biofilm formation and drug tolerance independently. Moreover, findings suggested the periplasmic sensory HmsP domain of SagS is likely to be the control point in the regulation of biofilm formation and biofilm cells transitioning to a drug-tolerant state. We thus asked whether specific amino acid residues present in the HmsP domain contribute to the switch function of SagS. HmsP domain residues were therefore subjected to alanine replacement mutagenesis to identify substitutions that block the sensory function(s) of SagS, which is apparent by attached cells being unable to develop mature biofilms and/or prevent transition to an antimicrobial-resistant state. Mutant analyses revealed 32 residues that only contribute to blocking one sensory function. Moreover, amino acid residues affecting attachment and subsequent biofilm formation but not biofilm tolerance also impaired histidine kinase signaling via BfiS. In contrast, residues affecting biofilm drug tolerance but not attachment and subsequent biofilm formation negatively impacted BrlR transcription factor levels. Structure prediction suggested the two sets of residues affecting sensory functions are located in distinct areas that were previously described as being involved in ligand binding interactions. Taken together, these studies identify the molecular basis for the dual regulatory function of SagS. IMPORTANCE The membrane-bound sensory protein SagS plays a pivotal role in P. aeruginosa biofilm formation and biofilm cells gaining their heightened resistance to antimicrobial agents, with SagS being the control point at which both pathways diverge. Here, we demonstrate for the first time that the two

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

Science.gov (United States)

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

2016-03-01

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

Access to residual carrier concentration in ZnO nanowires by calibrated scanning spreading resistance microscopy

Energy Technology Data Exchange (ETDEWEB)

Wang, L., E-mail: lin.wang@insa-lyon.fr; Brémond, G. [Institut des Nanotechnologies de Lyon (INL), Université de Lyon, CNRS UMR 5270, INSA Lyon, Bat. Blaise Pascal, 7 Avenue Jean Capelle, 69621 Villeurbanne (France); Chauveau, J. M. [Centre de Recherche sur l' Hétéro-Epitaxie et ses Applications (CRHEA), CNRS UPR10, rue Bernard Grégory 06560 Valbonne Sophia Antipolis (France); Physics Department, University of Nice Sophia Antipolis (UNS), Parc Valrose, 06103 Nice (France); Brenier, R. [Institut Lumière Matière (ILM), Université de Lyon, CNRS UMR 5306, Université Claude Bernard Lyon 1, 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne (France); Sallet, V.; Jomard, F.; Sartel, C. [Groupe d' Étude de la Matière Condensée (GEMaC), CNRS-Université de Versailles St Quentin en Yvelines, Université Paris-Saclay, 45 Avenue des Etats-Unis, 78035 Versailles (France)

2016-03-28

Scanning spreading resistance microscopy (SSRM) was performed on non-intentionally doped (nid) ZnO nanowires (NWs) grown by metal-organic chemical vapor deposition in order to measure their residual carrier concentration. For this purpose, an SSRM calibration profile has been developed on homoepitaxial ZnO:Ga multilayer staircase structures grown by molecular beam epitaxy. The Ga density measured by SIMS varies in the 1.7 × 10{sup 17 }cm{sup −3} to 3 × 10{sup 20 }cm{sup −3} range. From measurements on such Ga doped multi-layers, a monotonic decrease in SSRM resistance with increasing Ga density was established, indicating SSRM being a well-adapted technique for two dimensional dopant/carrier profiling on ZnO at nanoscale. Finally, relevant SSRM signal contrasts were detected on nid ZnO NWs, and the residual carrier concentration is estimated in the 1–3 × 10{sup 18 }cm{sup −3} range, in agreement with the result from four-probe measurements.

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

Science.gov (United States)

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

2006-05-05

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

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

DEFF Research Database (Denmark)

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

2014-01-01

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

Influence of drug concentration on the diffusion parameters of caffeine

Science.gov (United States)

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

2011-01-01

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

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

Directory of Open Access Journals (Sweden)

Gayol, M. F.

2013-12-01

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

Polycyclic Aromatic Hydrocarbon Residues in Serum Samples of Autopsied Individuals from Tennessee

Directory of Open Access Journals (Sweden)

Aramandla Ramesh

2014-12-01

Full Text Available This study reports the concentrations of Polycyclic Aromatic Hydrocarbons (PAHs in human blood sera samples (n = 650 obtained at autopsy from individuals who died of drug abuse, alcohol toxicity, homicide, suicide and other unknown causes. The analyzed samples from decedents revealed the presence of PAHs of which B(aP was the most predominant one, followed by benzo(bfluoranthene and benzo(kfluoranthene. The other PAHs detected sporadically and measured were benzo(g,h,iperylene, acenaphthene, anthracene, phenanthrene, and fluoranthene The mean concentrations of PAHs were greater in the twenties to fifties age groups compared to others. The PAH residue levels detected were high in African Americans compared to Caucasians, Asians, and Hispanics. It appears that environmental exposure, dietary intake and in some cases occupational exposure may have contributed to the PAH body burden. While the PAH residue concentrations measured fall within the range of those reported for healthy adults elsewhere, in isolated cases, the concentrations detected were high, calling the need for a reduction in PAH emissions and human biomonitoring studies for purposes of risk assessment.

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

Science.gov (United States)

Reig, Milagro; Toldrá, Fidel

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

Residual effects of hypnotics: an update.

Science.gov (United States)

Hindmarch, I

1991-07-01

The sedative/hypnotic benzodiazepines introduced worldwide in the early 1960s were acclaimed for their low chemical toxicity and safety in clinical use. A decade later, some researchers and clinicians found that while all the drugs had undoubted potency and efficacy as sleep inducers and maintainers, the trade-off in residual effects (e.g., excessive daytime tiredness, poor concentration, impaired psychomotor performance, lowered mental abilities) was cause for concern. These sequelae not only affected patients' safety and ability to perform daytime tasks, but were also counter-therapeutic; the daytime sleep that was produced interfered with the natural nocturnal sleep. In a recent study, the degree to which patient abilities were impaired was measured by a number of psychomotor tests. Benzodiazepines with a duration of clinical effect of less than 8 to 10 hours produced fewer, less frequent residual effects than those with a measurable activity in excess of the normal nocturnal sleep period.

Residual Neurocognitive Features of Long-Term Ecstasy Users With Minimal Exposure to Other Drugs

Science.gov (United States)

Halpern, John H.; Sherwood, Andrea R.; Hudson, James I.; Gruber, Staci; Kozin, David; Pope, Harrison G.

2010-01-01

Aims In field studies assessing cognitive function in illicit ecstasy users, there are several frequent confounding factors that might plausibly bias the findings toward an overestimate of ecstasy-induced neurocognitive toxicity. We designed an investigation seeking to minimize these possible sources of bias. Design We compared illicit ecstasy users and non-users while 1) excluding individuals with significant lifetime exposure to other illicit drugs or alcohol; 2) requiring that all participants be members of the “rave” subculture; and 3) testing all participants with breath, urine, and hair samples at the time of evaluation to exclude possible surreptitious substance use. We compared groups with adjustment for age, gender, race/ethnicity, family-of-origin variables, and childhood history of conduct disorder and attention deficit hyperactivity disorder. We provide significance levels without correction for multiple comparisons. Setting Field study. Participants Fifty-two illicit ecstasy users and 59 non-users, age 18-45. Measurements Battery of 15 neuropsychological tests tapping a range of cognitive functions. Findings We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic-self-regulation, possibly reflecting increased impulsivity. However this finding might have reflected a premorbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug. Conclusions In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users. This finding contrasts with many previous findings—including our own—and emphasizes the need for continued caution in interpreting field studies of cognitive function in illicit ecstasy users. PMID:21205042

Analysis of banned veterinary drugs and herbicide residues in shellfish by liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatography-tandem mass spectrometry (GC/MS/MS)

International Nuclear Information System (INIS)

Chang, Geng-Ruei; Chen, Hui-Shan; Lin, Feng-Yi

2016-01-01

Seafood safety is a crucial public health concern for consumers. In this study, we applied a validated method to analyze the residue of banned veterinary drugs in shellfish, namely chloramphenicol, malachite green, leucomalachite green, and nitrofuran metabolites; additionally, the QuEChERS method was employed to detect 76 herbicides by LC/MS/MS and GC/MS/MS. In total, 42 shellfish samples, which included hard clams, freshwater clams, and oysters, were collected from aquafarms and production areas in Taiwan during 2012. Our results revealed 3.8 ng/g of chloramphenicol in one hard clam, 19.9–32.1 ng/g of ametryn in two hard clams, 16.1–60.1 ng/g of pendimethalin in four hard clams, and 17.0 ng/g of mefenacet in one oyster, indicating that 19.1% of the samples contained residues from banned veterinary drugs and pesticides. These data can be used to monitor the residue of veterinary drugs and pesticides in aquatic organisms and as a reference for food safety. - Highlights: • A certified method was employed for analyzing residues of banned veterinary drugs and herbicides in shellfish samples. • The trace levels of chloramphenicol, ametryn, pendimethalin were detected in hard clam samples. • For ensuring food safety, continual monitoring of aquatic products is necessary.

ABC transporter Cdr1p harbors charged residues in the intracellular loop and nucleotide-binding domain critical for protein trafficking and drug resistance.

Science.gov (United States)

Shah, Abdul Haseeb; Banerjee, Atanu; Rawal, Manpreet Kaur; Saxena, Ajay Kumar; Mondal, Alok Kumar; Prasad, Rajendra

2015-08-01

The ABC transporter Cdr1 protein of Candida albicans, which plays a major role in antifungal resistance, has two transmembrane domains (TMDs) and two nucleotide-binding domains (NBDs). The 12 transmembrane helices of TMDs that are interconnected by extracellular and intracellular loops (ICLs) mainly harbor substrate recognition sites where drugs bind while cytoplasmic NBDs hydrolyze ATP which powers drug efflux. The coupling of ATP hydrolysis to drug transport requires proper communication between NBDs and TMDs typically accomplished by ICLs. This study examines the role of cytoplasmic ICLs of Cdr1p by rationally predicting the critical residues on the basis of their interatomic distances. Among nine pairs that fall within a proximity of trafficking. These results point to a new role for ICL/NBD interacting residues in PDR ABC transporters in protein folding and trafficking. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

Science.gov (United States)

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 (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.

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

Science.gov (United States)

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

2014-05-01

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

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

Science.gov (United States)

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

2017-08-30

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

Residual gravimetric method to measure nebulizer output.

Science.gov (United States)

Vecellio None, Laurent; Grimbert, Daniel; Bordenave, Joelle; Benoit, Guy; Furet, Yves; Fauroux, Brigitte; Boissinot, Eric; De Monte, Michele; Lemarié, Etienne; Diot, Patrice

2004-01-01

The aim of this study was to assess a residual gravimetric method based on weighing dry filters to measure the aerosol output of nebulizers. This residual gravimetric method was compared to assay methods based on spectrophotometric measurement of terbutaline (Bricanyl, Astra Zeneca, France), high-performance liquid chromatography (HPLC) measurement of tobramycin (Tobi, Chiron, U.S.A.), and electrochemical measurements of NaF (as defined by the European standard). Two breath-enhanced jet nebulizers, one standard jet nebulizer, and one ultrasonic nebulizer were tested. Output produced by the residual gravimetric method was calculated by weighing the filters both before and after aerosol collection and by filter drying corrected by the proportion of drug contained in total solute mass. Output produced by the electrochemical, spectrophotometric, and HPLC methods was determined after assaying the drug extraction filter. The results demonstrated a strong correlation between the residual gravimetric method (x axis) and assay methods (y axis) in terms of drug mass output (y = 1.00 x -0.02, r(2) = 0.99, n = 27). We conclude that a residual gravimetric method based on dry filters, when validated for a particular agent, is an accurate way of measuring aerosol output.

Residues of tritium-labeled morantel in lactating dairy cattle

International Nuclear Information System (INIS)

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

1987-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2003-07-01

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

Comparison of questionnaire-based estimation of pesticide residue intake from fruits and vegetables with urinary concentrations of pesticide biomarkers.

Science.gov (United States)

Chiu, Yu-Han; Williams, Paige L; Mínguez-Alarcón, Lidia; Gillman, Matthew; Sun, Qi; Ospina, Maria; Calafat, Antonia M; Hauser, Russ; Chavarro, Jorge E

2018-01-01

We developed a pesticide residue burden score (PRBS) based on a food frequency questionnaire and surveillance data on food pesticide residues to characterize dietary exposure over the past year. In the present study, we evaluated the association of the PRBS with urinary concentrations of pesticide biomarkers. Fruit and vegetable (FV) intake was classified as having high (PRBS≥4) or low (PRBSEARTH study. Two urine samples per man were analyzed for seven biomarkers of organophosphate and pyrethroid insecticides, and the herbicide 2,4-dichlorophenoxyacetic acid. We used generalized estimating equations to analyze the association of the PRBS with urinary concentrations of pesticide biomarkers. Urinary concentrations of pesticide biomarkers were positively related to high pesticide FV intake but inversely related to low pesticide FV intake. The molar sum of urinary concentrations of pesticide biomarkers was 21% (95% confidence interval (CI): 2%, 44%) higher for each one serving/day increase in high pesticide FV intake, and 10% (95% CI: 1%, 18%) lower for each one serving/day increase in low pesticide FV intake. Furthermore, intake of high pesticide FVs positively related to most individual urinary biomarkers. Our findings support the usefulness of the PRBS approach to characterize dietary exposure to select pesticides.

Effectiveness of control strategies against Botrytis cinerea in vineyard and evaluation of the residual fungicide concentrations.

Science.gov (United States)

Gabriolotto, Chiara; Monchiero, Matteo; Negre, Michele; Spadaro, Davide; Gullino, Maria Lodovica

2009-05-01

This investigation was undertaken to test different control strategies against Botrytis cinerea vineyards. Two commercial vineyards, "Barbera" and "Moscato," located in Piedmont (Northern Italy) were divided into seven plots and treated with different combinations of fungicides including fenhexamid, pyrimethanil, fludioxonil + cyprodinil, iprodione, and boscalid, a new carboxamide compound. An integrated strategy including a chemical (pyrimethanil) and a biocontrol agent (Trichoderma spp. t2/4ph1) was also included. At harvest, the percentage of bunches and berries attacked by B. cinerea and the concentration of the chemical fungicides were determined. All the pesticide residues at harvest were below the maximum residue level (MRL), except when two applications of pyrimethanil per season were applied. Boscalid was the most effective active ingredient against B. cinerea among the tested chemicals. When boscalid application was followed by a treatment with pyrimethanil, its efficacy was similar to that shown by two treatments of pyrimethanil. However, this second strategy was not feasible due to the risks of resistance development in the pathogen and to the residue accumulation as indicated by the analysis.

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

Science.gov (United States)

DeCou, J; Johnson, K

2017-01-01

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

Calibration and LOD/LOQ estimation of a chemiluminescent hybridization assay for residual DNA in recombinant protein drugs expressed in E. coli using a four-parameter logistic model.

Science.gov (United States)

Lee, K R; Dipaolo, B; Ji, X

2000-06-01

Calibration is the process of fitting a model based on reference data points (x, y), then using the model to estimate an unknown x based on a new measured response, y. In DNA assay, x is the concentration, and y is the measured signal volume. A four-parameter logistic model was used frequently for calibration of immunoassay when the response is optical density for enzyme-linked immunosorbent assay (ELISA) or adjusted radioactivity count for radioimmunoassay (RIA). Here, it is shown that the same model or a linearized version of the curve are equally useful for the calibration of a chemiluminescent hybridization assay for residual DNA in recombinant protein drugs and calculation of performance measures of the assay.

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

Energy Technology Data Exchange (ETDEWEB)

Moznine, R El [School of Pharmacy, De Montfort University, Leiceste (United Kingdom); Smith, G [School of Pharmacy, De Montfort University, Leicester (United Kingdom); Polygalov, E [School of Pharmacy, De Montfort University, Leicester (United Kingdom); Suherman, P M [School of Pharmacy, De Montfort University, Leicester (United Kingdom); Broadhead, J [AstraZeneca Charnwood R and D, Bakewell Rd, Loughborough (United Kingdom)

2003-02-21

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 deg. C-T{sub g}). 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.

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

Science.gov (United States)

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

2017-11-01

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

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

Directory of Open Access Journals (Sweden)

Husniye Imamoglu

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Sagar Dhakal

2018-02-01

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

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

Science.gov (United States)

Dhakal, Sagar; Chao, Kuanglin; Huang, Qing; Kim, Moon; Schmidt, Walter; Qin, Jianwei; Broadhurst, C Leigh

2018-02-01

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

Escherichia Coli-Lux Biosensor Used to Monitor the Cytotoxicity and Genotoxicity of Pharmacological Residues in Environment

Directory of Open Access Journals (Sweden)

Eliza Hawrylik

2018-05-01

Full Text Available The aim of the study was to evaluate the usefulness of Escherichia coli K-12 RFM 443 recA::lux for cytotoxicity and genotoxicity monitoring of metoprolol in the environment. Metoprolol is one of the most popular cardiac drug which belongs to the group of β–blockers. The drug was applied at concentrations ranging from 0.01 µg/cm3 to 100 µg/cm3. The conducted studies are preliminary studies aimed at validation of the recA::lux gene construct in the direction of determining its sensitivity to metoprolol. The drug concentrations were selected experimentally to obtain a positive luminescence response. Obtained data indicated the influence of metoprolol on lux gene expression and recA promoter activity based on the use of laboratory samples using PBS buffer. Results indicate a potential possibility of using a bacterial biosensor Escherichia coli K - 12 RFM 443 with recA::lux gene fusion in cytotoxicity and genotoxicity monitoring of the cardiac drugs residue in the environment.

Radiological Modeling for Determination of Derived Concentration Levels of an Area with Uranium Residual Material - 13533

Energy Technology Data Exchange (ETDEWEB)

Perez-Sanchez, Danyl [CIEMAT, Avenida Complutense 40, 28040, Madrid (Spain)

2013-07-01

As a result of a pilot project developed at the old Spanish 'Junta de Energia Nuclear' to extract uranium from ores, tailings materials were generated. Most of these residual materials were sent back to different uranium mines, but a small amount of it was mixed with conventional building materials and deposited near the old plant until the surrounding ground was flattened. The affected land is included in an area under institutional control and used as recreational area. At the time of processing, uranium isotopes were separated but other radionuclides of the uranium decay series as Th-230, Ra-226 and daughters remain in the residue. Recently, the analyses of samples taken at different ground's depths confirmed their presence. This paper presents the methodology used to calculate the derived concentration level to ensure that the reference dose level of 0.1 mSv y-1 used as radiological criteria. In this study, a radiological impact assessment was performed modeling the area as recreational scenario. The modelization study was carried out with the code RESRAD considering as exposure pathways, external irradiation, inadvertent ingestion of soil, inhalation of resuspended particles, and inhalation of radon (Rn-222). As result was concluded that, if the concentration of Ra-226 in the first 15 cm of soil is lower than, 0.34 Bq g{sup -1}, the dose would not exceed the reference dose. Applying this value as a derived concentration level and comparing with the results of measurements on the ground, some areas with a concentration of activity slightly higher than latter were found. In these zones the remediation proposal has been to cover with a layer of 15 cm of clean material. This action represents a reduction of 85% of the dose and ensures compliance with the reference dose. (authors)

Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

International Nuclear Information System (INIS)

Slatter, J.G.; Sams, J.P.; Easter, J.A.

2003-01-01

Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [ 14 C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [ 14 C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [ 14 C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled 14 CO 2 . After 7 daily [ 14 C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C max and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

Assessment of radioactive residues arising from radiolabel instability in a multiple dose tissue distribution study in rats

Energy Technology Data Exchange (ETDEWEB)

Slatter, J.G. [Pharmacia Corp., Peapack, NJ (United States); Sams, J.P.; Easter, J.A. [Pharmacia Corp., Kalamazoo, MI (United States)] [and others

2003-05-01

Our study objectives were to quantitatively determine the effect of radiolabel instability on terminal phase radioactive tissue residues in a multiple dose tissue distribution study, to quantitatively compare tissue residue artifacts (non drug-related radioactivity) from two chemically-distinct radiolabel locations, and to conduct a definitive multiple dose tissue distribution study using the better of the two radiolabeled compounds. We compared the excretion and tissue distribution in rats of [{sup 14}C]linezolid, radiolabeled in two different locations, after 7 consecutive once daily [{sup 14}C] oral doses. The radiolabels were in the acetamide (two carbon) and oxazolidinone (isolated carbon) functional groups. Terminal phase tissue residue and excretion data were compared to data from rats dosed orally with [{sup 14}C]sodium acetate. Drug-related radioactivity was excreted rapidly over 24 h. After a single dose, the acetamide and oxazolidinone radiolabel sites both gave 3% of dose as exhaled {sup 14}CO{sub 2}. After 7 daily [{sup 14}C] oral doses, terminal phase radioactive tissue residues were higher from the acetamide radiolabel, relative to the oxazolidinone radiolabel, and were primarily not drug-related. In the definitive tissue distribution study, low concentrations of drug-related radioactivity in skin and thyroid were observed. We conclude that although small amounts of radiolabel instability do not significantly affect single dose tissue radioactivity C{sub max} and area under the curve (AUC), artifacts arising from radiolabel instability can prolong the apparent terminal phase half life and complicate study data interpretation. When possible, it is always preferable to use a completely stable radiolabel site. (author)

Evaluation of the Presence and Levels of Enrofloxacin, Ciprofloxacin, Sulfaquinoxaline and Oxytetracycline in Broiler Chickens after Drug Administration.

Science.gov (United States)

de Assis, Débora Cristina Sampaio; da Silva, Guilherme Resende; Lanza, Isabela Pereira; Ribeiro, Ana Cláudia Dos Santos Rossi; Lana, Ângela Maria Quintão; Lara, Leonardo José Camargos; de Figueiredo, Tadeu Chaves; Cançado, Silvana de Vasconcelos

2016-01-01

The depletion times of enrofloxacin and its metabolite ciprofloxacin as well as sulfaquinoxaline and oxytetracycline were evaluated in broiler chickens that had been subjected to pharmacological treatment. The presence and residue levels of these drugs in muscle tissue were evaluated using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method that was validated in this work. The results showed the presence of all antimicrobial residues; however, the presence of residues at concentrations higher than the drugs' maximum residue limit (MRL) of 100 μg kg-1 was found only during the treatment period for oxytetracycline and until two days after discontinuation of the medication for enrofloxacin, ciprofloxacin and sulfaquinoxaline. It was concluded that the residues of all antimicrobials were rapidly metabolized from the broiler muscles; after four days of withdrawal, the levels were lower than the limit of quantification (LOQ) of the method for the studied analytes.

The use of antimicrobial drugs in agriculture.

Science.gov (United States)

Black, W D

1984-08-01

Antibacterial drugs have been used widely in animal production for treatment and prevention of disease and for growth promotion. Concern has been expressed about possible harm to humans, through the use of drugs, in the following ways: increased microbial drug resistance; drug residues in food; allergic reactions and sensitization to antimicrobials; and drug toxicity. Research has shown that microbial resistance in people can develop from drugs used in animals. Farmers, butchers, etc., have been shown to have an increased incidence of drug-resistant organisms. Resistance to antibiotics can develop in two ways; genetic mutation and natural selection, and through R-factor plasmid transfer. Allergic reactions have been reported following the ingestion of penicillin-containing milk; however, residues in other foods have not caused allergic reactions. Sensitization of humans to antimicrobials through the consumption of drug residues in foods has never been documented. Evidence suggests that the residue levels in food are too low to cause sensitization. Drug toxicity, other than allergic reactions, appears not to result from residues of antimicrobial drugs in food. While it has been studied many times, monitoring programs have failed to find any evidence of a problem. This appears to reflect the low toxicity of these agents and the small amounts obtained in the food, however, it could also reflect failure of the monitoring systems.

21 CFR 173.250 - Methyl alcohol residues.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Methyl alcohol residues. 173.250 Section 173.250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) FOOD.... Methyl alcohol may be present in the following foods under the conditions specified: (a) In spice...

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

DEFF Research Database (Denmark)

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

2010-01-01

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

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

Directory of Open Access Journals (Sweden)

Ji-Hoon Lee

2017-07-01

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

9 CFR 318.20 - Use of animal drugs.

Science.gov (United States)

2010-01-01

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

High-throughput untargeted screening of veterinary drug residues and metabolites in tilapia using high resolution orbitrap mass spectrometry.

Science.gov (United States)

Jia, Wei; Chu, Xiaogang; Chang, James; Wang, Perry G; Chen, Ying; Zhang, Feng

2017-03-08

An analytical method was developed and validated for simultaneous analysis of one hundred and thirty-seven veterinary drug residues and metabolites from sixteen different classes in tilapia utilizing an improved fully non-targeted way of data acquisition with fragmentation. The automated on-line extraction procedure was achieved in a simple disposable pipet extraction. Ultrahigh-performance liquid chromatography and electrospray ionization quadrupole Orbitrap high-resolution mass spectrometry (UHPLC Q-Orbitrap) was used for the separation and detection of all the analytes. The methodology was validated by taking into consideration the guidelines specified in European SANCO/12571/2013 Guideline 2013 and Commission Decision 2002/657/EC. The extraction recoveries ranged from 81% to 111%. The limits of decision ranged from 0.01 to 2.73 μg kg -1 and the detection capabilities ranged from 0.01 to 4.73 μg kg -1 . The one hundred and thirty-seven compounds behave dynamic 0.1-500 μg kg -1 , with correlation coefficient >0.99. The fully non-targeted data acquisition way improves both sensitivity and selectivity for the fragments, which is beneficial for screening performance and identification capability. This validated method has been successfully applied on screening of veterinary drug residues and metabolites in muscle of tilapia, an important and intensively produced fish in aquaculture. Copyright © 2017 Elsevier B.V. All rights reserved.

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

DEFF Research Database (Denmark)

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

2017-01-01

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

Human-use antibacterial residues in the natural environment of China: implication for ecopharmacovigilance.

Science.gov (United States)

Wang, Jun; He, Bingshu; Hu, Xiamin

2015-06-01

Antibacterial residues in the natural environment have been of increasing concern due to their impact on bacteria resistance development and toxicity to natural communities and ultimately to public health. China is a large country with high production and consumption of antibacterials for its population growth and economic development in recent years. In this article, we summarized the current situation of human-use antibacterial pollution in Chinese water (wastewaters, natural and drinking waters) and solid matrices (sludge, sediment, and soil) reported in 33 peer-reviewed papers. We found that, although there are adequate wastewater treatment systems in China, human-use antibacterial residues in the natural environment were reported almost throughout the whole country. Three most frequently prescribed classes of antibacterials in China, including quinolones, macrolides, and β-lactam, were also the predominant classes of residues in Chinese environment, manifested as the high concentration and detection frequency. In view of this alarming situation, we have presented that ecopharmacovigilance (EPV) might be implemented in the antibacterial drug administration of China, as the active participation of the pharmaceutical industry and drug regulatory authorities from the diffuse source of antibacterial pollution. Considering EPV experience of developed countries together with the actual conditions of China, we have identified some approaches that can be taken, including:• Focus on education;• Further strengthening and persevering the antibacterial stewardship strategies and pharmaceutical take-back programs in China;• Designing greener antibacterials with better degradability in the environment;• Implementing environmental risk assessment prior to launch of new drugs;• Strengthening collaboration in EPV-related areas.

In silico analysis of conformational changes induced by mutation of aromatic binding residues: consequences for drug binding in the hERG K+ channel.

Directory of Open Access Journals (Sweden)

Kirsten Knape

Full Text Available Pharmacological inhibition of cardiac hERG K(+ channels is associated with increased risk of lethal arrhythmias. Many drugs reduce hERG current by directly binding to the channel, thereby blocking ion conduction. Mutation of two aromatic residues (F656 and Y652 substantially decreases the potency of numerous structurally diverse compounds. Nevertheless, some drugs are only weakly affected by mutation Y652A. In this study we utilize molecular dynamics simulations and docking studies to analyze the different effects of mutation Y652A on a selected number of hERG blockers. MD simulations reveal conformational changes in the binding site induced by mutation Y652A. Loss of π-π-stacking between the two aromatic residues induces a conformational change of the F656 side chain from a cavity facing to cavity lining orientation. Docking studies and MD simulations qualitatively reproduce the diverse experimentally observed modulatory effects of mutation Y652A and provide a new structural interpretation for the sensitivity differences.

Residues in food derived from animals

International Nuclear Information System (INIS)

Grossklaus, D.

1989-01-01

The first chapter presents a survey of fundamentals and methods of the detection and analysis of residues in food derived from animals, also referring to the resulting health hazards to man, and to the relevant legal provisions. The subsequent chapters have been written by experts of the Federal Health Office, each dealing with particular types of residues such as those of veterinary drugs, additives to animal feeds, pesticide residues, and with environmental pollutants and the contamination of animal products with radionuclides. (MG) With 35 figs., 61 tabs [de

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

Science.gov (United States)

Kullik, Sigrun A; Belknap, Andrew M

2017-03-01

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

Contamination profiles, mass loadings, and sewage epidemiology of neuropsychiatric and illicit drugs in wastewater and river waters from a community in the Midwestern United States.

Science.gov (United States)

Skees, Allie J; Foppe, Katelyn S; Loganathan, Bommanna; Subedi, Bikram

2018-08-01

In this study, residues of the neuropsychiatric and illicit drugs including stimulants, opioids, hallucinogens, antischizophrenics, sedatives, and antidepressants were determined in influent and effluent samples from a small wastewater treatment plant, a receiving creek, and river waters in the Four Rivers region of the Midwestern United States. Nineteen neuropsychiatric drugs, eight illicit drugs, and three metabolites of illicit drugs were detected and quantitated in the water samples using HPLC-MS/MS. Residual concentrations of the drugs varied from below the detection limit to sub-μg/L levels. The source of residual cocaine and benzoylecgonine in wastewater is primarily from human consumption of cocaine rather than direct disposal. Wastewater based epidemiology is utilized to estimate the community usage of drugs based on the concentration of drug residues in wastewater, wastewater inflow, and the population served by the centralized wastewater treatment plant. The per-capita consumption rate of methamphetamine (1740 mg/d/1000 people) and amphetamine (970 mg/d/1000 people) found in this study were the highest reported per-capita consumption rates in the USA. Antidepressant venlafaxine found to have the highest environmental emission from the WWTP (333 ± 160 mg/d/1000 people) followed by citalopram (132 ± 60.2 mg/d/1000 people), methamphetamine (111 ± 43.6 mg/d/1000 people), and hydrocodone (108 ± 90.1 mg/d/1000 people). Bee Creek, an immediate receiving water body, is found to be a source of several neuropsychiatric and illicit drugs including methamphetamine, methadone, alprazolam, oxazepam, temazepam, carbamazepine, venlafaxine, citalopram, sertraline, oxycodone, and hydrocodone (p < 0.036) in the Clarks River. Copyright © 2018 Elsevier B.V. All rights reserved.

Simultaneous screening and confirmation of multiple classes of drug residues in fish by liquid chromatography-ion trap mass spectrometry.

Science.gov (United States)

Smith, Shani; Gieseker, Charles; Reimschuessel, Renate; Decker, Christie-Sue; Carson, Mary C

2009-11-13

LC-ion trap mass spectrometry was used to screen and confirm 38 compounds from a variety of drug classes in four species of fish: trout, salmon, catfish, and tilapia. Samples were extracted with acetonitrile and hexane. The acetonitrile phase was evaporated, redissolved in water and acetonitrile, and analyzed by gradient chromatography on a phenyl column. MS(2) or MS(3) spectra were monitored for each compound. Qualitative method performance was evaluated by the analysis over several days of replicate samples of control fish, fish fortified with a drug mixture at 1 ppm, 0.1 ppm and 0.01 ppm, and fish dosed with a representative from each drug class. Half of the 38 drugs were confirmed at 0.01 ppm, the lowest fortification level. This included all of the quinolones and fluoroquinolones, the macrolides, malachite green, and most of the imidazoles. Florfenicol amine, metronidazole, sulfonamides, tetracyclines, and most of the betalactams were confirmed at 0.1 ppm. Ivermectin and penicillin G were only detectable in the 1 ppm fortified samples. With the exception of amoxicillin, emamectin, metronidazole, and tylosin, residue presence was confirmed in all the dosed fish.

Detection of pyridaben residue levels in hot pepper fruit and leaves by liquid chromatography-tandem mass spectrometry: effect of household processes.

Science.gov (United States)

Kim, Sung-Woo; Abd El-Aty, A M; Rahman, Md Musfiqur; Choi, Jeong-Heui; Choi, Ok-Ja; Rhee, Gyu-Seek; Chang, Moon-Ik; Kim, Heejung; Abid, Morad D N; Shin, Sung Chul; Shim, Jae-Han

2015-07-01

Following quick, easy, cheap, effective, rugged and safe (QuEChERS) and LC/MS/MS analysis, pyridaben residual levels were determined in unprocessed and processed hot pepper fruit and leaves. The linearities were satisfactory with determination coefficients (R(2)) in excess of 0.995 in processed and unprocessed pepper fruit and leaves. Recoveries at various concentrations were 79.9-105.1% with relative standard deviations ≤15%. The limits of quantitation of 0.003-0.012 mg/kg were very low compared with the maximum residue limits (2-5 mg/kg) set by the Ministry of Food and Drug Safety, Republic of Korea. The effects of various household processes, including washing, blanching, frying and drying under different conditions (water volume, blanching time and temperature) on residual concentrations were evaluated. Both washing and blanching (in combination with high water volume and time factor) significantly reduced residue levels in hot pepper fruit and leaves compared with other processes. In sum, the developed method was satisfactory and could be used to accurately detect residues in unprocessed and processed pepper fruit and leaves. It is recommended that pepper fruit/leaves be blanched after washing before being consumed to protect consumers from the negative health effects of detected pesticide residues. Copyright © 2014 John Wiley & Sons, Ltd.

Drug diffusion across skin with diffusivity spatially modulated

Science.gov (United States)

Montoya Arroyave, Isabel

2014-05-01

A diffusion and delivery model of a drug across the skin with diffusivity spatially modulated is formulated and solved analytically using computer algebra. The model is developed using one-dimensional diffusion equation with a diffusivity which is a function of position in the skin; with an initial condition which is describing that the drug is initially contained inside a therapeutic patch; with a boundary condition according to which the change in concentration in the patch is minimal, such that assumption of zero flux at the patch-skin interface is valid; and with other boundary condition according to which the microcirculation in the capillaries just below the dermis carries the drug molecules away from the site at a very fast rate, maintaining the inner concentration at 0. The model is solved analytically by the method of the Laplace transform, with Bromwich integral and residue theorem. The concentration profile of the drug in the skin is expressed as an infinite series of Bessel functions. The corresponding total amount of delivered drug is expressed as an infinite series of decreasing exponentials. Also, the corresponding effective time for the therapeutic patch is determined. All computations were performed using computer algebra software, specifically Maple. The analytical results obtained are important for understanding and improving currentapplications of therapeutic patches. For future research it is interesting to consider more general models of spatial modulation of the diffusivity and the possible application of other computer algebra software such as Mathematica and Maxima.

Using mutagenesis to explore conserved residues in the RNA-binding groove of influenza A virus nucleoprotein for antiviral drug development

Science.gov (United States)

Liu, Chia-Lin; Hung, Hui-Chen; Lo, Shou-Chen; Chiang, Ching-Hui; Chen, I.-Jung; Hsu, John T.-A.; Hou, Ming-Hon

2016-02-01

Nucleoprotein (NP) is the most abundant type of RNA-binding viral protein in influenza A virus-infected cells and is necessary for viral RNA transcription and replication. Recent studies demonstrated that influenza NP is a valid target for antiviral drug development. The surface of the groove, covered with numerous conserved residues between the head and body domains of influenza A NP, plays a crucial role in RNA binding. To explore the mechanism by which NP binds RNA, we performed a series of site-directed mutagenesis in the RNA-binding groove, followed by surface plasmon resonance (SPR), to characterize the interactions between RNA and NP. Furthermore, a role of Y148 in NP stability and NP-RNA binding was evaluated. The aromatic residue of Y148 was found to stack with a nucleotide base. By interrupting the stacking interaction between Y148 and an RNA base, we identified an influenza virus NP inhibitor, (E, E)-1,7-bis(4-hydroxy-3-methoxyphenyl) -1,6-heptadiene-3,5-dione; this inhibitor reduced the NP’s RNA-binding affinity and hindered viral replication. Our findings will be useful for the development of new drugs that disrupt the interaction between RNA and viral NP in the influenza virus.

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

Science.gov (United States)

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

2014-08-01

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

Using higher doses to compensate for tubing residuals in extended-infusion piperacillin-tazobactam.

Science.gov (United States)

Lam, Wendy J; Bhowmick, Tanaya; Gross, Alan; Vanschooneveld, Trevor C; Weinstein, Melvin P

2013-06-01

To mathematically assess drug losses due to infusion line residuals and evaluate methods to compensate for drug loss due to residual volumes in intravenous pump tubing. Literature was accessed through Ovid MEDLINE (1996-February 2013), using combinations of the search terms tubing residuals, residual volume, residual medication, intravenous infusions, intravenous injections, piperacillin, piperacillin-tazobactam, β-lactams, equipment design, infusion pumps, extended infusion, extended administration, and prolonged infusion. In addition, select reference citations from publications identified were reviewed. All articles that involved extended-infusion piperacillin-tazobactam implementation strategies were included in the review. Infusion pump characteristics and tubing residuals can affect extended-infusion piperacillin-tazobactam dosing strategies. Two studies addressing tubing residuals were identified. Both studies recommended increasing infusion volumes to compensate for tubing residuals. One study also recommended decreasing infusion-line dead space by using alternative infusion pump systems. Study calculations suggest that higher doses of piperacillin-tazobactam may be used to account for medication left in tubing residuals if alternative infusion pump systems cannot be obtained, and increased infusion volumes are not an option. Extended-infusion piperacillin-tazobactam has been used as a method of maximizing pharmacodynamic target attainment. Use of higher doses of piperacillin-tazobactam may be a reasonable method to compensate for drug loss due to residual volumes in large-bore intravenous pump tubing.

Statistical inference on residual life

CERN Document Server

Jeong, Jong-Hyeon

2014-01-01

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

Residues of carcinogenic animal drugs in food: difficulties in evaluation of human safety.

Science.gov (United States)

Somogyi, A

1979-01-01

The indisputable need to intensify animal production in order to provide an adequate food supply for the world population involves the use of substances that are highly potent pharmacologically and toxicologically. The history of regulatory action with regard to such additives is similar to that for other substances: first, no regulation; next, an over-reaction; and now decisions based on judicious evaluation of scientific facts. One factor that differentiates the chemicals used in animal production from other food additives is that both the parent compounds and their metabolites appear in edible products, posing problems both for the analytical detection and safety evaluation of such residues. It would be unrealistic to propose 'zero' tolerances for these additives, even if they are carcinogenic. The benefits gained from drugs that cure and prevent infections and parasitic diseases in food-producing animals, and the fact that analytical methods can now detect very small quantities make the presence of low levels of these substances in food unobjectionable.

Residue analysis of orthosulfamuron herbicide in fatty rice using liquid chromatography–tandem mass spectrometry

Directory of Open Access Journals (Sweden)

Young-Jun Lee

2015-05-01

Full Text Available In the present study, orthosulfamuron residues were extracted from fatty (unpolished rice and rice straw using a modified QuEChERS method and analyzed using liquid chromatography–tandem mass spectrometry. The matrix-matched calibration was linear over the concentration ranges of 0.01–2.0 mg/kg with determination coefficient (R2 ⩾ 0.997. The recovery rates at two fortification levels (0.1 and 0.5 mg/kg were satisfactory and ranged between 88.1% and 100.6%, with relative standard deviation (RSD <8%. The limit of quantitation, 0.03 mg/kg, was lower than the maximum residue limit, 0.05 mg/kg, set by the Ministry of Food and Drug Safety in the Republic of Korea. The developed method was applied successfully to field samples harvested at 116 days and none of the samples were positive for the residue.

Hanford tank residual waste - Contaminant source terms and release models

International Nuclear Information System (INIS)

Deutsch, William J.; Cantrell, Kirk J.; Krupka, Kenneth M.; Lindberg, Michael L.; Jeffery Serne, R.

2011-01-01

Highlights: → Residual waste from five Hanford spent fuel process storage tanks was evaluated. → Gibbsite is a common mineral in tanks with high Al concentrations. → Non-crystalline U-Na-C-O-P ± H phases are common in the U-rich residual. → Iron oxides/hydroxides have been identified in all residual waste samples. → Uranium release is highly dependent on waste and leachant compositions. - Abstract: Residual waste is expected to be left in 177 underground storage tanks after closure at the US Department of Energy's Hanford Site in Washington State, USA. In the long term, the residual wastes may represent a potential source of contamination to the subsurface environment. Residual materials that cannot be completely removed during the tank closure process are being studied to identify and characterize the solid phases and estimate the release of contaminants from these solids to water that might enter the closed tanks in the future. As of the end of 2009, residual waste from five tanks has been evaluated. Residual wastes from adjacent tanks C-202 and C-203 have high U concentrations of 24 and 59 wt.%, respectively, while residual wastes from nearby tanks C-103 and C-106 have low U concentrations of 0.4 and 0.03 wt.%, respectively. Aluminum concentrations are high (8.2-29.1 wt.%) in some tanks (C-103, C-106, and S-112) and relatively low ( 2 -saturated solution, or a CaCO 3 -saturated water. Uranium release concentrations are highly dependent on waste and leachant compositions with dissolved U concentrations one or two orders of magnitude higher in the tests with high U residual wastes, and also higher when leached with the CaCO 3 -saturated solution than with the Ca(OH) 2 -saturated solution. Technetium leachability is not as strongly dependent on the concentration of Tc in the waste, and it appears to be slightly more leachable by the Ca(OH) 2 -saturated solution than by the CaCO 3 -saturated solution. In general, Tc is much less leachable (<10 wt.% of the

Study on recovering directly the commercial cerium oxide and total of residue rare earths from Dongpao bastnasite concentrate

International Nuclear Information System (INIS)

Nguyen Trong Hung; Nguyen Thanh Chung; Luu Xuan Dinh

2003-01-01

A technology for decomposition roasting and sequential leaching processes of Dong Pao bastnasite concentrate to recover directly commercial cerium oxide and total of residue rare earth elements from the leaching solution of the roasted product have been investigated. The bastnasite concentrate is initially roasted at temperature range of 600 - 650 degC and for time of 4 hrs in order to decompose and convert the hardly soluble carbonate forms of ore into easily soluble oxide. The roasted solid is then leached with sulfuric acid solution of 6N at 60 degC for 4 hrs to convert rare earths in oxide and fluoride form into rare earth sulfate. The recovery yield of rare earths of these stages is more than 95%. The attention has especially been paid on recovering directly the commercial cerium oxide and total of residue rare earth element from the above leaching solution. Complex ions of CeSO 4 2+ , Ce(SO 4 ) 2 , Ce(SO 4 ) 3 2- and Ce(SO 4 ) 4 4- exist in aqueous solution of cerium (IV) sulfate. Based on the property, the method of ion - sieve with DOWEX cation resin column has been applied to estimating separation of the ceric complex anions from Ln(III). The survey showed that most of the ceric complex anions are separated from total of residue rare earths. The latter which are absorbed in the cation column are recovered by elution of HCl of 4N. The recovery yield of cerium can only be reached 20% but the purity of that is very high, can be reached 99.6%. About 5 kg of CeO 2 of high grade and 5 kg of TREO of commercial specification have been produced. (author)

Quantitative and qualitative determination of enrofloxacin residues in fish tissues

OpenAIRE

Đorđević Vesna; Baltić M.; Ćirković M.; Kilibarda Nataša; Glamočlija Nataša; Stefanović S.; Miščević Mirjana

2009-01-01

Presence of enrofloxacin residues in fish liver, kidney and muscle tissue was investigated after per os application of the drug. For the purpose of determination of enrofloxacin, the following analytical methods were used: microbiological method - plate pH 8 with Escherichia coli ATCC 11303 and HPLC method with fluorescence detection. After a 5-day oral treatment of carps, enrofloxacin residues in tissues were determined up to the 10th day after the end of the drug application. Enrofloxacin c...

Targeted delivery of anti-tuberculosis drugs to macrophages: targeting mannose receptors

Science.gov (United States)

Filatova, L. Yu; Klyachko, N. L.; Kudryashova, E. V.

2018-04-01

The development of systems for targeted delivery of anti-tuberculosis drugs is a challenge of modern biotechnology. Currently, these drugs are encapsulated in a variety of carriers such as liposomes, polymers, emulsions and so on. Despite successful in vitro testing of these systems, virtually no success was achieved in vivo, because of low accessibility of the foci of infection located in alveolar macrophage cells. A promising strategy for increasing the efficiency of therapeutic action of anti-tuberculosis drugs is to encapsulate the agents into mannosylated carriers targeting the mannose receptors of alveolar macrophages. The review addresses the methods for modification of drug substance carriers, such as liposomes and biodegradable polymers, with mannose residues. The use of mannosylated carriers to deliver anti-tuberculosis agents increases the drug circulation time in the blood stream and increases the drug concentration in alveolar macrophage cells. The bibliography includes 113 references.

Widespread occurrence of chemical residues in beehive matrices from apiaries located in different landscapes of Western France.

Directory of Open Access Journals (Sweden)

Olivier Lambert

Full Text Available The honey bee, Apis mellifera, is frequently used as a sentinel to monitor environmental pollution. In parallel, general weakening and unprecedented colony losses have been reported in Europe and the USA, and many factors are suspected to play a central role in these problems, including infection by pathogens, nutritional stress and pesticide poisoning. Honey bee, honey and pollen samples collected from eighteen apiaries of western France from four different landscape contexts during four different periods in 2008 and in 2009 were analyzed to evaluate the presence of pesticides and veterinary drug residues.A multi-residue analysis of 80 compounds was performed using a modified QuEChERS method, followed by GC-ToF and LC-MS/MS. The analysis revealed that 95.7%, 72.3% and 58.6% of the honey, honey bee and pollen samples, respectively, were contaminated by at least one compound. The frequency of detection was higher in the honey samples (n = 28 than in the pollen (n = 23 or honey bee (n = 20 samples, but the highest concentrations were found in pollen. Although most compounds were rarely found, some of the contaminants reached high concentrations that might lead to adverse effects on bee health. The three most frequent residues were the widely used fungicide carbendazim and two acaricides, amitraz and coumaphos, that are used by beekeepers to control Varroa destructor. Apiaries in rural-cultivated landscapes were more contaminated than those in other landscape contexts, but the differences were not significant. The contamination of the different matrices was shown to be higher in early spring than in all other periods.Honey bees, honeys and pollens are appropriate sentinels for monitoring pesticide and veterinary drug environmental pollution. This study revealed the widespread occurrence of multiple residues in beehive matrices and suggests a potential issue with the effects of these residues alone or in combination on honey bee health.

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

Science.gov (United States)

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

2014-04-01

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

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

Science.gov (United States)

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

2017-10-01

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

Low-residue euthanasia of stranded mysticetes.

Science.gov (United States)

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.

Forensic analysis of high explosives residues in post-blast water samples employing solid phase extraction for analyte pro-concentration

International Nuclear Information System (INIS)

Umi Kalsom Ahmad; Rajendran, Sumathy; Ling, Lee Woan

2008-01-01

Nitro aromatic, nitramine and nitrate ester compounds are a major group of high order explosive or better known as military explosives. Octahydro-1,3,5,7-tetrazocine (HMX), 1,3,5-hexahydro-1,3,5-trinitro triazine (RDX), 2,4,6-trinitro-toluene (TNT), pentaerythritol tetranitrate (PETN) and 2,4-dinitrotoluene (2,4-DNT) are secondary high explosives classified as most commonly used explosives components. There is an increasing demand for pre-concentration of these compounds in water samples as the sensitivity achieved by instrumental analytical methods for these high explosives residues are the main drawback in the application at trace levels for forensic analysis. Hence, a simple cartridge solid phase extraction (SPE) procedure was optimized as the off-line extraction and pre-concentration method to enhance the detection limit of high explosive residues using micellar electrokinetic chromatography (MEKC) and gas chromatography with electron-capture detection (GC-ECD) methods. The SPE cartridges utilized LiChrolut EN as the SPE adsorbent. By emplying pre-concentration using SPE, the detection limits of the target analytes in water sample were lowered by more than 1000 times with good percentage recovery (>87%) for MEKC method and lowered by 120 times with more than 2 % percentage recovery for GC-ECD methods. In order to test the feasibility of the developed method to real cases, post-blast water samples were analyzed. The post-blast water samples which were collected from Baling Bom training range, Ulu Kinta, Perak contained RDX and PETN in the range of 0.05 - 0.17 ppm and 0.0124 - 0.0390 ppm respectively. (author)

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

Science.gov (United States)

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

2017-05-01

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

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

Science.gov (United States)

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

2018-02-13

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

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

Science.gov (United States)

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

2016-08-01

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

Decomposition of dilute residual active chlorine in sea-water

International Nuclear Information System (INIS)

Yoshinaga, Tetsutaro; Kawano, Kentaro; Yanagase, Kenjiro; Shiga, Akira

1985-01-01

Coastal industries such as power stations require enormous quantities of sea-water for cooling, but the marine organisms in it often result in fouling and/or blockade of the circulating water condenser and pipeworks. To prevent this, chlorine, or hypochlorite by the direct electrolysis of sea-water have been added. Environmental concerns, however, dictate that the residual chlorine concentration at the outlet should be less than the regulated value (0.02 ppm). Methods for decomposing dilute residual chlorine solutions were therefore studied. It was found that: 1) The addition of (raw) sea-water to the sea-water which passed through the condenser lowered the residual chlorine concentration to an greater extent than could be expected by dilution only. 2) Ozonation of the residual chlorine solution led to degradation of OCl - , but in solutions with a residual chlorine concentrations of less than 3 -- 4 ppm, ozonation had no effect. 3) Irradiation with ultra violet light (254 nm) decomposed the residual chlorine. Under the present work conditions (25 0 C: pH 8; depth 10 mm), nearly first order kinetics were to hold [da/dt = ksub((1)) (1-a)sup(n)]. There is a proportional relationship between the kinetic constant (k) and illuminous intensity (L), i.e., ksub((1))[C 0 sup(Cl 2 ): 10 ppm] = 6.56 x 10 -5 L (L = 0 -- 1000 lx). Thus, the use of both sea-water addition and UV irradiation provides a probable method for decomposing a residual chlorine to the expected concentration. (author)

Americium recovery from reduction residues

Science.gov (United States)

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)

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

Science.gov (United States)

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

2016-11-01

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

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

Science.gov (United States)

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

2017-03-01

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

Experimental study on effect of roasting, boiling and microwave cooking methods on enrofloxacin antibiotic residues in edible poultry tissues

Directory of Open Access Journals (Sweden)

A Javadi

2011-11-01

Full Text Available The purpose of this study was to determine the effects of different cooking processes such as boiling, roasting and microwaving on enrofloxacin residues in muscle, liver and gizzard tissues of broiler chickens. Each of chicks was fed by routine diet and water with %0.05 of enrofloxacine for consecutive 5 days .Then; three locations including breast muscle, liver and gizzard were sampled aseptically from each carcass. Enrofloxacin residue was analyzed using microbial method by plates seeded with Escherichia coli. After doing different phases of the test on raw samples, the positive raw samples cooked by various cooking procedures and we surveyed cooked samples with similar method again for present of residue. The results were show reduction in concentration of enrofloxacin residue after different cooking processes. The most reduction of the residue in cooked meat and gizzard samples related to boiling process and roasting process for cooked liver samples and the highest detectable amount of residue belonged to microwaving process in all cooked samples. Regarding to the results of this study, we can conclude that cooking processes can’t annihilate total amounts of these drug and it can only decrease their amounts and the most of residue in boiling process excreted from tissue to cooking fluid.

Plasma dispositions and concentrations of ivermectin in eggs following treatment of laying hens.

Science.gov (United States)

Cirak, V Y; Aksit, D; Cihan, H; Gokbulut, C

2018-05-01

To determine the plasma disposition and concentrations of ivermectin (IVM) in eggs produced by laying hens following S/C, oral and I/V administration. Twenty-four laying hens, aged 37 weeks and weighing 1.73 (SD 0.12) kg were allocated to three groups of eight birds. The injectable formulation of IVM was administered either orally, S/C, or I/V, at a dose of 0.2 mg/kg liveweight, following dilution (1:5, v/v) with propylene glycol. Heparinised blood samples were collected at various times between 0.25 hours and 20 days after drug administration. Eggs produced by hens were also collected daily throughout the study period. Samples of plasma and homogenised egg were analysed using HPLC. Maximum concentrations of IVM in plasma and mean residence time of IVM were lower after oral (10.2 (SD 7.2) ng/mL and 0.38 (SD 0.14) days, respectively) than after S/C (82.9 (SD 12.4) ng/mL and 1.05 (SD 0.24) days, respectively) administration (pV administration, and until 15 days after S/C administration. Peak concentrations of IVM were 15.7, 23.3 and 1.9 µg/kg, observed 2, 5 and 4 days after I/V, S/C and oral administration, respectively. The low plasma bioavailability of IVM observed after oral administration in laying hens could result in lower efficacy or subtherapeutic plasma concentrations, which may promote the development of parasitic drug resistance. Due to high IVM residues in eggs compared to the maximum residue limits for other food-producing animal species, a withdrawal period should be necessary for eggs after IVM treatment in laying hens.

Prediction of residue-residue contact matrix for protein-protein interaction with Fisher score features and deep learning.

Science.gov (United States)

Du, Tianchuan; Liao, Li; Wu, Cathy H; Sun, Bilin

2016-11-01

Protein-protein interactions play essential roles in many biological processes. Acquiring knowledge of the residue-residue contact information of two interacting proteins is not only helpful in annotating functions for proteins, but also critical for structure-based drug design. The prediction of the protein residue-residue contact matrix of the interfacial regions is challenging. In this work, we introduced deep learning techniques (specifically, stacked autoencoders) to build deep neural network models to tackled the residue-residue contact prediction problem. In tandem with interaction profile Hidden Markov Models, which was used first to extract Fisher score features from protein sequences, stacked autoencoders were deployed to extract and learn hidden abstract features. The deep learning model showed significant improvement over the traditional machine learning model, Support Vector Machines (SVM), with the overall accuracy increased by 15% from 65.40% to 80.82%. We showed that the stacked autoencoders could extract novel features, which can be utilized by deep neural networks and other classifiers to enhance learning, out of the Fisher score features. It is further shown that deep neural networks have significant advantages over SVM in making use of the newly extracted features. Copyright © 2016. Published by Elsevier Inc.

Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

Energy Technology Data Exchange (ETDEWEB)

Chatterjee, Sagnik, E-mail: Sagnik.Chatterjee@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Richert, Lysiane, E-mail: l.richert@kaly-cell.com [KaLy-Cell, 20A rue du Général Leclerc, 67115 Plobsheim (France); Augustijns, Patrick, E-mail: Patrick.Augustijns@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium); Annaert, Pieter, E-mail: Pieter.Annaert@pharm.kuleuven.be [Drug Delivery and Disposition, KU Leuven Department of Pharmaceutical and Pharmacological Sciences, O and N2, Herestraat 49 — bus 921, 3000 Leuven (Belgium)

2014-01-01

Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

Hepatocyte-based in vitro model for assessment of drug-induced cholestasis

International Nuclear Information System (INIS)

Chatterjee, Sagnik; Richert, Lysiane; Augustijns, Patrick; Annaert, Pieter

2014-01-01

Early detection of drug-induced cholestasis remains a challenge during drug development. We have developed and validated a biorelevant sandwich-cultured hepatocytes- (SCH) based model that can identify compounds causing cholestasis by altering bile acid disposition. Human and rat SCH were exposed (24–48 h) to known cholestatic and/or hepatotoxic compounds, in the presence or in the absence of a concentrated mixture of bile acids (BAs). Urea assay was used to assess (compromised) hepatocyte functionality at the end of the incubations. The cholestatic potential of the compounds was expressed by calculating a drug-induced cholestasis index (DICI), reflecting the relative residual urea formation by hepatocytes co-incubated with BAs and test compound as compared to hepatocytes treated with test compound alone. Compounds with clinical reports of cholestasis, including cyclosporin A, troglitazone, chlorpromazine, bosentan, ticlopidine, ritonavir, and midecamycin showed enhanced toxicity in the presence of BAs (DICI ≤ 0.8) for at least one of the tested concentrations. In contrast, the in vitro toxicity of compounds causing hepatotoxicity by other mechanisms (including diclofenac, valproic acid, amiodarone and acetaminophen), remained unchanged in the presence of BAs. A safety margin (SM) for drug-induced cholestasis was calculated as the ratio of lowest in vitro concentration for which was DICI ≤ 0.8, to the reported mean peak therapeutic plasma concentration. SM values obtained in human SCH correlated well with reported % incidence of clinical drug-induced cholestasis, while no correlation was observed in rat SCH. This in vitro model enables early identification of drug candidates causing cholestasis by disturbed BA handling. - Highlights: • Novel in vitro assay to detect drug-induced cholestasis • Rat and human sandwich-cultured hepatocytes (SCH) as in vitro models • Cholestatic compounds sensitize SCH to toxic effects of accumulating bile acids • Drug

Determination of neomycin residues in pasteurized milks produced in some dairy processing establishments in East-Azarbaijan Province, Iran

Directory of Open Access Journals (Sweden)

M.H Movassagh

2014-11-01

Full Text Available Antibiotic residues in milk have a potential hazard for the consumer and may cause allergic reactions, interference in the intestinal flora that result in development of resistant populations of bacteria, thereby rendering antibiotic treatment ineffective. The aim of this study was to determine neomycin residues in pasteurized milk in East-Azarbaijan province. For this, a total of 200 samples of pasteurized milk produced by five dairy processing establishments of East Azarbaijan province was randomly collected. The samples were obtained over the spring and autumn (100 samples for each season of 2010. First, antibiotic residues were determined by Copan milk test. Afterwards, the competitive ELISA assay was used for the determination of neomycin concentration in positive samples. Of all samples, neomycin residues were observed in 9 and 13 samples and the mean neomycin residues amount were 43.20 ± 8.10 and 26.63±2.08 µg/L in spring and autumn, respectively. According to the limit of neomycin (1500 µg/l in cow raw milk in Iran, despite all the remaining drugs in pasteurized milk, in any of the samples exceeded level of neomycin was not observed.Based on the results, continuousmonitoringofantibiotic residues inmilk samples is recommended.

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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

NARCIS (Netherlands)

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

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

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.....

Science.gov (United States)

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...

Radionuclides in Bayer process residues: previous analysis for radiological protection

International Nuclear Information System (INIS)

Cuccia, Valeria; Rocha, Zildete; Oliveira, Arno H. de

2011-01-01

Natural occurring radionuclides are present in many natural resources. Human activities may enhance concentrations of radionuclides and/or enhance potential of exposure to naturally occurring radioactive material (NORM). The industrial residues containing radionuclides have been receiving a considerable global attention, because of the large amounts of NORM containing wastes and the potential long term risks of long-lived radionuclides. Included in this global concern, this work focuses on the characterization of radioactivity in the main residues of Bayer process for alumina production: red mud and sand samples. Usually, the residues of Bayer process are named red mud, in their totality. However, in the industry where the samples were collected, there is an additional residues separation: sand and red mud. The analytical techniques used were gamma spectrometry (HPGe detector) and neutron activation analysis. The concentrations of radionuclides are higher in the red mud than in the sand. These solid residues present activities concentrations enhanced, when compared to bauxite. Further uses for the residues as building material must be more evaluated from the radiological point of view, due to its potential of radiological exposure enhancement, specially caused by radon emission. (author)

Residue analysis of veterinary drugs and growth-promoting agents

NARCIS (Netherlands)

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

2007-01-01

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

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

Directory of Open Access Journals (Sweden)

Zuzana Slivová

2015-01-01

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

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

International Nuclear Information System (INIS)

Niklas, Jens; Noor, Fozia; Heinzle, Elmar

2009-01-01

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

Effect of cooking on residues of the quinolones oxolinic acid and flumequine in fish.

Science.gov (United States)

Steffenak, I; Hormazabal, V; Yndestad, M

1994-01-01

The effect of cooking on residues of the quinolones oxolinic acid and flumequine in fish was investigated. Salmon containing residues of oxolinic acid and flumequine was boiled or baked in the oven. Samples of raw and cooked muscle, skin, and bone, as well as of the water in which the fish was boiled and juice from the baked fish, were analysed. Oxolinic acid and flumequine did not degrade at the temperatures reached when cooking the fish. However, fish muscle free from drug residues may be contaminated during boiling and baking due to leakage of the drug from reservoirs in the fish.

Residue preference mapping of ligand fragments in the Protein Data Bank.

Science.gov (United States)

Wang, Lirong; Xie, Zhaojun; Wipf, Peter; Xie, Xiang-Qun

2011-04-25

The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables unprecedented possibilities for new insights. Herein, we applied molecule-fragmentation algorithms to split the ligands extracted from PDB crystal structures into small fragments. Subsequently, we have developed a ligand fragment and residue preference mapping (LigFrag-RPM) algorithm to map the profiles of the interactions between these fragments and the 20 proteinogenic amino acid residues. A total of 4032 fragments were generated from 71 798 PDB ligands by a ring cleavage (RC) algorithm. Among these ligand fragments, 315 unique fragments were characterized with the corresponding fragment-residue interaction profiles by counting residues close to these fragments. The interaction profiles revealed that these fragments have specific preferences for certain types of residues. The applications of these interaction profiles were also explored and evaluated in case studies, showing great potential for the study of protein-ligand interactions and drug design. Our studies demonstrated that the fragment-residue interaction profiles generated from the PDB ligand fragments can be used to detect whether these fragments are in their favorable or unfavorable environments. The algorithm for a ligand fragment and residue preference mapping (LigFrag-RPM) developed here also has the potential to guide lead chemistry modifications as well as binding residues predictions.

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

Science.gov (United States)

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

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Derek M Foster

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

Analysis of fenbendazole residues in bovine milk by ELISA.

Science.gov (United States)

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

2002-10-09

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.

Quantitative determination of quinolones residues in milk by HPLC-FLD

Directory of Open Access Journals (Sweden)

Marilena Gili

2012-10-01

Full Text Available Veterinary drugs have become an integral part of the livestock production and play an important role in maintenance of animal welfare. The use of veterinary medicines may be cause of the presence of drug residues in animal food products if appropriate withdrawal periods are not respected or if contaminated feeds are used. This work presents the development of an HPLC-FLD method for the quantitative de-tection of eight quinolones – norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, difloxacin, oxolinic acid, nalidixic acid, flumequine– in bovine milk. After deproteination and extraction with a metaphos-phoric acid 1% w/v / methanol / acetonitrile (60/20/20 v/v/v solution, the sample is partially evaporated and cleaned up on a reversed phase SPE cartridge.The extract is analyzed using an high performance liquid chromatograph with fluorescence detector. Mean recovery ranged between 65% - 88%. All the an-alytes can be identified and quantified in the concentration range 15 - 60 μg/Kg for danofloxacin and 25 - 150 μg/Kg for the other quinolones.

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

Science.gov (United States)

Brouwers, Joachim; Tack, Jan; Augustijns, Patrick

2007-10-01

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

Studies on influence of environmental factors on concentration on concentration of radionuclides

International Nuclear Information System (INIS)

Anon.

1974-01-01

Environmental factors which seemed to influence the concentration of radionuclides to marine organisms including illumination, water temperature, coexisting stable elements, salt concentration, suspended matters in sea water and residue were studied. The influence of illumination was examined by algae using 137 Cs, 60 Co, 85 Sr, and 106 Ru as tracers, within 24 hours of illumination. The concentration of 137 Cs and 60 Co revealed remarkable increase of uptake in accordance with increasing illumination intensity, and 24 hours illumination showed 2 times concentration of that by 4 hours'. 85 Sr and 106 Ru showed no effect of illumination, and suggested their concentration was depending on adsorption to the surface. As for water temperature, the concentration factor of 65 Zn, 137 Cs obtained from fishes and shells by 22 0 C breeding was 2 times of that by 12 0 C breeding. Concerning the influence of coexisting stable elements, fishes and shells were examined by 54 Mn, 60 Co, and 65 Zn as tracers. When the stable elements concentration in sea water became 10 times the normal, concentration factor depending on adsorption and metabolism became respective one tenth and one second of the normal value. The influence of salt concentration was examined using 85 Sr, 65 Zn, and 137 Cs, and revealed that 28 to 40 per cent changes of salt level gave slight influence on concentration factor. In order to study the influence of suspended matters and quality of residue, 3 kinds of 106 Ru complex species were added. Concentration factor of Hijiki (Hijikia fusiforme) showed no remarkable difference between breeding in filtrated and non-filtrated sea water. However, clams living in the sand should be taken care of the concentration by the residue in the sea bottom. (Kanao, N.)

Daily Intake of Protein from Cod Residual Material Lowers Serum Concentrations of Nonesterified Fatty Acids in Overweight Healthy Adults: A Randomized Double-Blind Pilot Study

Directory of Open Access Journals (Sweden)

Iselin Vildmyren

2018-06-01

Full Text Available Improved process technologies have allowed fishing vessels to utilize residuals from cod fillet production (head, backbone, skin, cuttings, and entrails and convert this to high-quality protein powders for human consumption. In this double-blind pilot study, 42 healthy overweight or obese adults were randomized to three experimental groups consuming tablets corresponding to 6 g/day of proteins from cod residuals as presscake meal (Cod-PC, presscake and stickwater meal (Cod-PCW, or placebo tablets (control for eight weeks. The primary outcome of this study was changes in metabolites related to glucose regulation in overweight or obese healthy adults after intake of proteins from cod residuals. Cod-PC supplementation decreased postprandial serum nonesterified fatty acids (NEFA concentration and increased gene expressions of diglyceride acyltransferase 1 and 2 in subcutaneous adipose tissue compared with controls. Fasting insulin increased while fasting NEFA and 120-min postprandial glucose decreased within the Cod-PC group, but these changes did not differ from the other groups. In conclusion, supplementation with Cod-PC beneficially affected postprandial serum NEFA concentration compared with the other groups in overweight or obese adults. Supplementation with Cod-PCW, which contains a higher fraction of water-soluble protein compared to Cod-PC, did not affect serum markers of glucose regulation.

Characterisation and management of concrete grinding residuals.

Science.gov (United States)

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

2018-02-01

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

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

International Nuclear Information System (INIS)

Corrans, I.J.; Levin, J.

1979-01-01

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

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

Science.gov (United States)

Lehotay, Steven J; Lightfield, Alan R

2018-01-01

The way to maximize scope of analysis, sample throughput, and laboratory efficiency in the monitoring of veterinary drug residues in food animals is to determine as many analytes as possible as fast as possible in as few methods as possible. Capital and overhead expenses are also reduced by using fewer instruments in the overall monitoring scheme. Traditionally, the highly polar aminoglycoside antibiotics require different chromatographic conditions from other classes of drugs, but in this work, we demonstrate that an ion-pairing reagent (sodium 1-heptanesulfonate) added to the combined final extracts from two sample preparation methods attains good separation of 174 targeted drugs, including 9 aminoglycosides, in the same 10.5-min ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The full method was validated in bovine kidney, liver, and muscle tissues according to US regulatory protocols, and 137-146 (79-84%) of the drugs gave between 70 and 120% average recoveries with ≤ 25% RSDs in the different types of tissues spiked at 0.5, 1, and 2 times the regulatory levels of interest (10-1000 ng/g depending on the drug). This method increases sample throughput and the possible number of drugs monitored in the US National Residue Program, and requires only one UHPLC-MS/MS method and instrument for analysis rather than two by the previous scheme. Graphical abstract Outline of the streamlined approach to monitor 174 veterinary drugs, including aminoglycosides, in bovine tissues by combining two extracts of the same sample with an ion-pairing reagent for analysis by UHPLC-MS/MS.

Development and characterization of a pre-treatment procedure to eliminate human monoclonal antibody therapeutic drug and matrix interference in cell-based functional neutralizing antibody assays.

Science.gov (United States)

Xu, Weifeng; Jiang, Hao; Titsch, Craig; Haulenbeek, Jonathan R; Pillutla, Renuka C; Aubry, Anne-Françoise; DeSilva, Binodh S; Arnold, Mark E; Zeng, Jianing; Dodge, Robert W

2015-01-01

Biological therapeutics can induce an undesirable immune response resulting in the formation of anti-drug antibodies (ADA), including neutralizing antibodies (NAbs). Functional (usually cell-based) NAb assays are preferred to determine NAb presence in patient serum, but are often subject to interferences from numerous serum factors, such as growth factors and disease-related cytokines. Many functional cell-based NAb assays are essentially drug concentration assays that imply the presence of NAbs by the detection of small changes in functional drug concentration. Any drug contained in the test sample will increase the total amount of drug in the assay, thus reducing the sensitivity of NAb detection. Biotin-drug Extraction with Acid Dissociation (BEAD) has been successfully applied to extract ADA, thereby removing drug and other interfering factors from human serum samples. However, to date there has been no report to estimate the residual drug level after BEAD treatment when the drug itself is a human monoclonal antibody; mainly due to the limitation of traditional ligand-binding assays. Here we describe a universal BEAD optimization procedure for human monoclonal antibody (mAb) drugs by using a LC-MS/MS method to simultaneously measure drug (a mutant human IgG4), NAb positive control (a mouse IgG), and endogenous human IgGs as an indicator of nonspecific carry-over in the BEAD eluate. This is the first report demonstrating that residual human mAb drug level in clinical sample can be measured after BEAD pre-treatment, which is critical for further BEAD procedure optimization and downstream immunogenicity testing. Copyright © 2014 Elsevier B.V. All rights reserved.

The undesirable effects of neuromuscular blocking drugs

DEFF Research Database (Denmark)

Claudius, C; Garvey, L H; Viby-Mogensen, J

2009-01-01

Neuromuscular blocking drugs are designed to bind to the nicotinic receptor at the neuromuscular junction. However, they also interact with other acetylcholine receptors in the body. Binding to these receptors causes adverse effects that vary with the specificity for the cholinergic receptor...... in question. Moreover, all neuromuscular blocking drugs may cause hypersensitivity reactions. Often the symptoms are mild and self-limiting but massive histamine release can cause systematic reactions with circulatory and respiratory symptoms and signs. At the end of anaesthesia, no residual effect...... of a neuromuscular blocking drug should be present. However, the huge variability in response to neuromuscular blocking drugs makes it impossible to predict which patient will suffer postoperative residual curarization. This article discusses the undesirable effects of the currently available neuromuscular blocking...

A fabric phase sorptive extraction-High performance liquid chromatography-Photo diode array detection method for the determination of twelve azole antimicrobial drug residues in human plasma and urine.

Science.gov (United States)

Locatelli, Marcello; Kabir, Abuzar; Innosa, Denise; Lopatriello, Teresa; Furton, Kenneth G

2017-01-01

This paper reports a novel fabric phase sorptive extraction-high performance liquid chromatography-photodiode array detection (FPSE-HPLC-PDA) method for the simultaneous extraction and analysis of twelve azole antimicrobial drug residues that include ketoconazole, terconazole, voriconazole, bifonazole, clotrimazole, tioconazole, econazole, butoconazole, miconazole, posaconazole, ravuconazole, and itraconazole in human plasma and urine samples. The selected azole antimicrobial drugs were well resolved by using a Luna C 18 column (250mm×4.6mm; 5μm particle size) in gradient elution mode within 36min. The analytical method was calibrated and validated in the range from 0.1 to 8μg/mL for all the drug compounds. Blank human plasma and urine were used as the sample matrix for the analysis; while benzyl-4-hydroxybenzoate was used as the internal standard (IS). The limit of quantification of the FPSE-HPLC-PDA method was found as 0.1μg/mL and the weighted-matrix matched standard calibration curves of the drugs showed a good linearity upto a concentration of 8μg/mL. The parallelism tests were also performed to evaluate whether overrange sample can be analyzed after dilution, without compromising the analytical performances of the validated method. The intra- and inter-day precision (RSD%) values were found ≤13.1% and ≤13.9%, respectively. The intra- and inter-day trueness (bias%) values were found in the range from -12.1% to 10.5%. The performances of the validated FPSE-HPLC-PDA were further tested on real samples collected from healthy volunteers after a single dose administration of itraconazole and miconazole. To the best of our knowledge, this is the first FPSE extraction procedure applied on plasma and urine samples for the simultaneous determination of twelve azole drugs possessing a wide range of logK ow values (extending from 0.4 for fluconazole to 6.70 of butoconazole) and could be adopted as a rapid and robust green analytical tool for clinical and

Hazardous properties of paint residues from the furniture industry.

Science.gov (United States)

Vaajasaari, Kati; Kulovaara, Maaret; Joutti, Anneli; Schultz, Eija; Soljamo, Kari

2004-01-30

The objective of this study was to screen nine excess paint residues for environmental hazard and to evaluate their disposability in a non-hazardous or hazardous-waste landfill. These residues were produced in the process of spray-painting furniture. Residues were classified according to their leaching and ecotoxicological properties. Leaching properties were determined with the European standard SFS-EN 12457-2 leaching-test. The toxicity of the leaching-test eluates was measured with plant-, bacteria- and enzyme-inhibition bioassays. Total organic carbon, formaldehyde and solvent concentrations in the solid wastes and in the leaching-test eluates were analysed. It seemed likely that leached formaldehyde caused very high acute toxicity in leaching-test eluates of the dry-booth residues. This hypothesis was based on the fact that the formaldehyde concentrations in the leaching-test eluates of the dry-booth residues were 62-75 times higher than the EC50 value reported in the literature for formaldehyde. The results of the water-curtain booth residues showed that the samples with the highest TOC and aromatic solvent concentrations were also the most toxic. The studied excess paint residues were complex organic mixtures and contained large amounts of compounds not identifiable from chemical data. Therefore, the evaluation of the hazard based solely on available chemical data is unlikely to be sufficient, as evidenced by our study. Our results show that harmful compounds remain in the solid waste and the toxicity results of their leaching-test eluates show that toxicity may leach from residues in contact with water at landfill sites. They also confirm the benefit of combining chemical and ecotoxicological assays in assessing the potential environmental hazard of complex organic mixtures found in wastes. Copyright 2003 Elsevier B.V.

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

Science.gov (United States)

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

2004-09-01

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

Quantitative determination of pefloxacin mesylate by residual-base neutralisation method

Directory of Open Access Journals (Sweden)

HULIKALCHANDRA SHEKAR PRAMEELA

2004-05-01

Full Text Available This work describes two procedures based on residual base determination for the quantification of pefloxacin mesylate (PFM in bulk drug and in pharmaceutical products. In the first method involving titrimetry, the drug solution is treated with a measured excess of sodium hydroxide followed by back titration of the residual base with hydrochloric acid using a phenol red-bromothymol blue mixed indicator. The second spectrophotometrie method involves treatment of a fixed amount of sodium hydroxide – phenol red mixture with varying amounts of the drug, and measuring the decrease in the absorbance of the dye at 560 nm. In the titrimetric method, a reaction stoichiometry of 1:1 was found in the quantification range of 4–20 mg of drug. The spectrophotometric method allows the determination of PFM in the 5–40 mg ml-1 range. The molar absorptivity is 5.91¤103 l mol-1 cm-1 and the Sandell sensitivity is 56.37 ng cm-2. The methods were applied successfully to the determination of PFM in pharmaceutical preparations.

Determination of Residual Chlorine and Turbidity in Drinking Water. Instructor's Manual.

Science.gov (United States)

Office of Water Program Operations (EPA), Cincinnati, OH. National Training and Operational Technology Center.

This instructor's guide presents analytical methods for residual chlorine and turbidity. Topics include sample handling, permissable concentration levels, substitution of residual chlorine for bacteriological work, public notification, and the required analytical techniques to determine residual chlorine and turbidity. This publication is intended…

Determination of Residual Chlorine and Turbidity in Drinking Water. Student Manual.

Science.gov (United States)

Office of Water Program Operations (EPA), Cincinnati, OH. National Training and Operational Technology Center.

This student's manual covers analytical methods for residual chlorine and turbidity. Topics include sample handling, permissable concentration levels, substitution of residual chlorine for bacteriological work, public notification, and the required analytical techniques to determine residual chlorine and turbidity. The publication is intended for…

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

Science.gov (United States)

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

2017-11-01

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

Survey of pyrethroid, macrocyclic lactone and antibacterial residues in bulk milk tank from Minas Gerais State, Brazil

Directory of Open Access Journals (Sweden)

Lidia C.A. Picinin

Full Text Available ABSTRACT: A survey of veterinary drug residues in bulk milk tank from Minas Gerais State, Brazil, was carried out through a broad scope analysis. Here, 132 raw milk samples were collected at 45 dairy farms in Minas Gerais from August 2009 to February 2010, and analyzed for 42 analytes, comprising pyrethroids, macrocyclic lactones and antibacterials, using liquid chromatography coupled with mass spectrometry in tandem mode and gas chromatography with electron capture detection. Within all milk samples, at least one veterinary drug residue was identified in 40 milk samples (30.30% by confirmatory tests, whereas 16 samples (12.12% showed the presence of at least two residues. With regard to the Brazilian maximum residue levels, 11 milk samples (8.33% were non-compliant according to Brazilian Legislation. The veterinary drugs detected in the non-compliant milk samples include penicillin V (one sample, abamectin (one sample and cypermethrin (nine samples. Furthermore, the antibacterial screening methods failed to identify most of the positive samples that were detected by confirmatory tests, leading to a large discrepancy between the screening and confirmatory antimicrobial tests. Thus, the present study indicated that the veterinary drugs residues still represents a great concern for the milk production chain.

Pesticide residue quantification analysis by hyperspectral imaging sensors

Science.gov (United States)

Liao, Yuan-Hsun; Lo, Wei-Sheng; Guo, Horng-Yuh; Kao, Ching-Hua; Chou, Tau-Meu; Chen, Junne-Jih; Wen, Chia-Hsien; Lin, Chinsu; Chen, Hsian-Min; Ouyang, Yen-Chieh; Wu, Chao-Cheng; Chen, Shih-Yu; Chang, Chein-I.

2015-05-01

Pesticide residue detection in agriculture crops is a challenging issue and is even more difficult to quantify pesticide residue resident in agriculture produces and fruits. This paper conducts a series of base-line experiments which are particularly designed for three specific pesticides commonly used in Taiwan. The materials used for experiments are single leaves of vegetable produces which are being contaminated by various amount of concentration of pesticides. Two sensors are used to collected data. One is Fourier Transform Infrared (FTIR) spectroscopy. The other is a hyperspectral sensor, called Geophysical and Environmental Research (GER) 2600 spectroradiometer which is a batteryoperated field portable spectroradiometer with full real-time data acquisition from 350 nm to 2500 nm. In order to quantify data with different levels of pesticide residue concentration, several measures for spectral discrimination are developed. Mores specifically, new measures for calculating relative power between two sensors are particularly designed to be able to evaluate effectiveness of each of sensors in quantifying the used pesticide residues. The experimental results show that the GER is a better sensor than FTIR in the sense of pesticide residue quantification.

Fermentative utilization of glycerol residue for the production of acetic acid

Science.gov (United States)

Irvan; Trisakti, B.; Hasibuan, R.; Joli, M.

2018-02-01

Glycerol residue, frequently known as pitch, is a waste produced from the downstream product of crude glycerine distillation. With the increasing need of pure glycerine in the world, the glycerol residue produced is also increasing. Glycerol residue is a solid waste at room temperature, highly alkaline (pH > 13), corrosive, and categorized as hazardous and poisonous waste. In this research, acetic acid was produced from glycerol residue through the anaerobic fermentation process by using purple non-sulphur photosynthetic bacteria. The purpose of this study was to find out the influence of concentration change of glycerol residue on time and to find out the possibility of glycerol residue to be utilized as acetic acid. In this research, at first 400 g of glycerol residue was diluted with 200 ml of distilled water to change the glycerine phase, from solid to liquid at room temperature, acidified by using hydrochloric acid until pH 2. The top layer formed was fatty acid and triglycerides that should be removed. Meanwhile, the bottom layer was diluted glycerol residue which was then neutralized with caustic soda. To produce acetic acid, glycerol residue with various concentrations, salt, and purple non-sulphur photosynthetic bacteria were put together into a 100 ml bottle which had been previously sterilized, then incubated for four weeks under the light of 40-watt bulb. The result showed that on the 28th day of fermentation, the produced acetic acid were 0.28, 1.85, and 0.2% (w/w) by using glycerine with the concentration of 0.5, 1.0, and 1.5% (w/w), respectively.

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

Science.gov (United States)

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. © 2013 American Academy of Forensic Sciences.

Magnetic solid-phase extraction based on carbon nanotubes for the determination of polyether antibiotic and s-triazine drug residues in animal food with LC-MS/MS.

Science.gov (United States)

Liu, Xiaoxing; Xie, Shuyu; Ni, Tengteng; Chen, Dongmei; Wang, Xu; Pan, Yuanhu; Wang, Yulian; Huang, Lingli; Cheng, Guyue; Qu, Wei; Liu, Zhenli; Tao, Yanfei; Yuan, Zonghui

2017-06-01

Carbon nanotubes-magnetic nanoparticles, comprising ferroferric oxide nanoparticles and carbon nanotubes, were prepared through a simple one-step synthesis method and subsequently applied to magnetic solid-phase extraction for the determination of polyether antibiotic and s-triazine drug residues in animal food coupled with liquid chromatography with tandem mass spectrometry. The nanocomposites were characterized by transmission electron microscopy, X-ray diffraction, and vibrating sample magnetometry. The components within the nanocomposites endowed the material with high extraction performance and manipulative convenience. Compared with carbon nanotubes, the as-prepared carbon nanotubes-magnetic nanoparticles showed better extraction and separation efficiencies for polyether antibiotics and s-triazine drugs thanks to the contribution of the iron-containing magnetic nanoparticles. Various experimental parameters affecting the extraction efficiency had been investigated in detail. Under the optimal conditions, the good linearity ranging from 1 to 200 μg/kg for diclazuril, toltrazuril, toltrazuril sulfone, lasalocid, monensin, salinomycin, narasin, nanchangmycin, and maduramicin, low limits of detection ranging from 1 to 5 μg/kg, and satisfactory spiked recoveries (77.1-91.2%, with the inter relative standard deviation values from 4.0 to 12.2%) were shown. It was confirmed that this novel method was an efficient pretreatment and enrichment procedure and could be successfully applied for extraction and determination of polyether and s-triazine drug residues in complex matrices. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evaluation of the Presence and Levels of Enrofloxacin, Ciprofloxacin, Sulfaquinoxaline and Oxytetracycline in Broiler Chickens after Drug Administration

Science.gov (United States)

da Silva, Guilherme Resende; Lanza, Isabela Pereira; Ribeiro, Ana Cláudia dos Santos Rossi; Lana, Ângela Maria Quintão; Lara, Leonardo José Camargos

2016-01-01

The depletion times of enrofloxacin and its metabolite ciprofloxacin as well as sulfaquinoxaline and oxytetracycline were evaluated in broiler chickens that had been subjected to pharmacological treatment. The presence and residue levels of these drugs in muscle tissue were evaluated using an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method that was validated in this work. The results showed the presence of all antimicrobial residues; however, the presence of residues at concentrations higher than the drugs’ maximum residue limit (MRL) of 100 μg kg-1 was found only during the treatment period for oxytetracycline and until two days after discontinuation of the medication for enrofloxacin, ciprofloxacin and sulfaquinoxaline. It was concluded that the residues of all antimicrobials were rapidly metabolized from the broiler muscles; after four days of withdrawal, the levels were lower than the limit of quantification (LOQ) of the method for the studied analytes. PMID:27846314

Pesticide residues in locally available cereals and vegetables

International Nuclear Information System (INIS)

Cunanan, S.A.; Santos, F.L.; Bonoan, L.S.

1976-03-01

Vegetable samples (pechay, cabbage, lettuce, green beans and tomatoes) bought from public markets in the Metro Manila area were analyzed for pesticide residues using gas chromatography. The samples analyzed in 1968-69 contained high levels of chlorinated pesticides such as DDT, Aldrin, Endrin, and Thiodan, while in the samples analyzed in January 1976, no chlorinated and organophosphate pesticides were detected. Cereal samples (rice, corn and sorghum) were obtained from the National Grains Authority and analyzed for pesticide residues and bromine residues. Total bromine residues was determined by neutron activation analysis. In most of the samples analyzed, the concentrations of pesticide residues were below the tolerance levels set by the FAO/WHO Committee on Pesticide Residues in Foods. An exception was one rice sample from Thailand, the bromine residue content (110ppm) of which exceeds the tolerance level of 50ppm

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

Directory of Open Access Journals (Sweden)

Canan Bural

2011-08-01

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

Residual stress in spin-cast polyurethane thin films

Energy Technology Data Exchange (ETDEWEB)

Zhang, Hong; Zhang, Li, E-mail: lizhang@mae.cuhk.edu.hk [Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Shatin N.T., Hong Kong (China); Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong, Shatin N.T., Hong Kong (China)

2015-01-19

Residual stress is inevitable during spin-casting. Herein, we report a straightforward method to evaluate the residual stress in as-cast polyurethane thin films using area shrinkage measurement of films in floating state, which shows that the residual stress is independent of radial location on the substrate and decreased with decreasing film thickness below a critical value. We demonstrate that the residual stress is developed due to the solvent evaporation after vitrification during spin-casting and the polymer chains in thin films may undergo vitrification at an increased concentration. The buildup of residual stress in spin-cast polymer films provides an insight into the size effects on the nature of polymer thin films.

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

Science.gov (United States)

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

2001-10-01

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

Release behavior of triazine residues in stabilised contaminated soils

International Nuclear Information System (INIS)

Ying, G.G.; Kookana, R.S.; Mallavarpu, M.

2005-01-01

This paper reports the release behavior of two triazines (atrazine and simazine) in stabilised soils from a pesticide-contaminated site in South Australia. The soils were contaminated with a range of pesticides, especially with triazine herbicides. With multiple extractions of each soil sample with deionised water (eight in total), 15% of atrazine and 4% of simazine residues were recovered, resulting in very high concentrations of the two herbicides in leachate. The presence of small fractions of surfactants was found to further enhance the release of the residues. Methanol content up to 10% did not substantially influence the concentration of simazine and atrazine released. The study demonstrated that while the stabilisation of contaminated soil with particulate activated carbon (5%) and cement mix (15%) was effective in locking the residues of some pesticides, it failed to immobilise triazine herbicides residues completely. Given the higher water solubility of these herbicides than other compounds more effective strategies to immobilise their residues is needed. - Stabilisation of contaminated soil with a mix of activated carbon and cement may fail to immobilise some contaminants like triazines

Endosulfan residues in fish from the MUDA rice agroecosystem

International Nuclear Information System (INIS)

Nashriyah Mat; Sabri Junoh; Nuriati Nurdin

2002-01-01

A study was carried out in the recycled and the non-recycled areas of the Muda rice agroecosystem to determine the residue level of endosulfan in rice field fish. Snakehead or haruan (Channa striata), climbing perch or puyu (Anabas testudineus), walking catfish or keli (Clariasspp.) and snakeskin gouramy or sepat siam (Trichogasterpectoralis) were sampled and the tissues analysed using Gas Liquid Chromatography. Endosulfan sulphate metabolite was a ubiquitous residue in all fish at levels ranging from 0.0065 μg/g to 0.9837 μg/g of tissue wet weight whilst α-isomer was detected at a much lower concentration followed by β-isomer. In Channa striata, endosulfan total residue (α+β+sulphate) was accumulated in fish tissues sampled at ACRBD4 (non-recycled) site followed by Blok 14 (recycled) site. Endosulfan residue concentration did not coincide with water recycling practice nor changes in EROD enzyme activity. (Author)

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

Directory of Open Access Journals (Sweden)

G. Prabhakar

2017-12-01

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

Matrix-Matching as an Improvement Strategy for the Detection of Pesticide Residues.

Science.gov (United States)

Giacinti, Géraldine; Raynaud, Christine; Capblancq, Sophie; Simon, Valérie

2016-05-01

More than 90% of the pesticides residues in apples are located in the peel. We developed a gas chromatography/ion trap tandem mass spectrometry method for investigating all detectable residues in the peel of 3 apple varieties. Sample preparation is based on the use of the Quick Easy Cheap Effective Rugged and Safe method on the whole fruit, the flesh, and the peel. Pesticide residues were quantified with solvent-matched and matrix-matched standards, by spiking apple sample extracts. Matrix effects dependent on the type of extract (fruit, flesh, or peel) and the apple variety were detected. The best data processing methods involved normalizing matrix effect rates by matrix-matched internal/external calibration. Boscalid, captan, chlorpyrifos, fludioxonil, and pyraclostrobin were the most frequently detected pesticides. However, their concentrations in the whole fruit were below European maximum residue levels. Despite negative matrix effects, the residues in peel were detected at concentrations up to 10 times higher than those in whole fruits. Consequently, other pesticide residues present at concentrations below the limit of quantification in the whole fruit were detected in the peel. © 2016 Institute of Food Technologists®

An overview of the main foodstuff sample preparation technologies for tetracycline residue determination.

Science.gov (United States)

Pérez-Rodríguez, Michael; Pellerano, Roberto Gerardo; Pezza, Leonardo; Pezza, Helena Redigolo

2018-05-15

Tetracyclines are widely used for both the treatment and prevention of diseases in animals as well as for the promotion of rapid animal growth and weight gain. This practice may result in trace amounts of these drugs in products of animal origin, such as milk and eggs, posing serious risks to human health. The presence of tetracycline residues in foods can lead to the transmission of antibiotic-resistant pathogenic bacteria through the food chain. In order to ensure food safety and avoid exposure to these substances, national and international regulatory agencies have established tolerance levels for authorized veterinary drugs, including tetracycline antimicrobials. In view of that, numerous sensitive and specific methods have been developed for the quantification of these compounds in different food matrices. One will note, however, that the determination of trace residues in foods such as milk and eggs often requires extensive sample extraction and preparation prior to conducting instrumental analysis. Sample pretreatment is usually the most complicated step in the analytical process and covers both cleaning and pre-concentration. Optimal sample preparation can reduce analysis time and sources of error, enhance sensitivity, apart from enabling unequivocal identification, confirmation and quantification of target analytes. The development and implementation of more environmentally friendly analytical procedures, which involve the use of less hazardous solvents and smaller sample sizes compared to traditional methods, is a rapidly increasing trend in analytical chemistry. This review seeks to provide an updated overview of the main trends in sample preparation for the determination of tetracycline residues in foodstuffs. The applicability of several extraction and clean-up techniques employed in the analysis of foodstuffs, especially milk and egg samples, is also thoroughly discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Recovery of sulfur from residue gases of low H/sub 2/S concentration

Energy Technology Data Exchange (ETDEWEB)

Bratzler, K; Doerges, A; Schlauer, J

1976-01-01

The Lucas process is intended for reduction of SO/sub 2/ and H/sub 2/S in Claus tail gas or other low-sulfur residue gases to levels below 200 ppm (H/sub 2/S only in traces). In the first stage, all sulfur compounds are burned to SO/sub 2/; in the second stage, a coke reactor reduces SO/sub 3/ and O/sub 2/; and in the third stage, the SO/sub 2/ is absorbed in an aqueous alkali phosphate solution. Concentrated SO/sub 2/ from regeneration of the solution is returned to the Claus plant, or can be catalystically reduced to elemental sulfur. The process was proven out in a semitechnical pilot plant, with satisfactory results as follows: sulfur recovery, 97 to 99.8%; energy consumption per 1,000 cu m feed gas, 2.6 to 3.7 kw-hr plus 860 to 930 MJ heating gas (however, 300 to 350 kg steam was generated); 0.15 kg chemicals; 0.7 to 1.5 kg coke; and a minimal amount of catalyst if sulfur is produced. Investment is only 60 to 80% of that in a 2-stage Claus process, with which the Lucas process is competitive.

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

Science.gov (United States)

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

2014-03-01

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

Natural radioactivity in petroleum residues

International Nuclear Information System (INIS)

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

2006-01-01

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

Monitoring of Benomyl Residue in Mushroom Marketed in Hamadan City

Directory of Open Access Journals (Sweden)

S. Abdi

2015-07-01

Full Text Available Introduction & Objective: Pesticide residues in environment and food have a negative impact on the health of living organisms. Therefore, this study was carried out for evaluation of benomyl residues in mushroom marketed in Hamadan city in 2014 using spectrophotometry. Materials & Methods: 10 specimens of mushroom were collected from greenhouses and market basket of Hamadan city. After preparation and processing the samples in the laboratory, be-nomyl residues in samples were determined using a spectrophotometric method in 3 replica-tions. All statistical analyses were performed using the SPSS statistical package. Results: The mean concentration of benomyl residues in samples were 5.90±0.75, 2.10± 0.487, 40.04±1.346, 0.32±0.044, 14.0±0.785, 1.54±0.304, 40.0±0.45, 0.87±0.055, 0.66± 0.032 and 49.60±0.303 µg kg-1 and more than the maximum residue limit (MRL provided by the World Health Organization (10 ppb. The results of the comparison of the mean concentration of pesticide residues among samples revealed significant differences in most of the samples (P<0.05. Conclusion: The results showed that mean concentrations of benomyl residues in mushroom samples were exceeding that of the MRL. Therefore, it is essential to impart proper education to the farming community about hazards involved in the overuse of toxic pesticides. Also, codification of laws and their enforcement and implementation of programs for the regular periodic monitoring of pesticide residues in foodstuffs especially in vegetables cultivated un-der greenhouse conditions at the national level to protect consumers’ health are recom-mended.(Sci J Hamadan Univ Med Sci 2015; 22 (2: 137-143

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

Energy Technology Data Exchange (ETDEWEB)

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

2014-08-01

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

Isotopic tracer aided studies of fenvalerate residues in stored rice

International Nuclear Information System (INIS)

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

1990-01-01

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

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

Science.gov (United States)

Quirk, Emma; Doggett, Adrian; Bretnall, Alison

2014-08-05

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

Nutritional potential of post extraction residues and silage from ...

African Journals Online (AJOL)

Nutritional potential of post extraction residues and silage from leaves of five cassava varieties as feed for ruminants. ... Results indicated that processing reduced (P < 0.05) the inherent nutrients of cassava leaf residues produced after the extraction of protein concentrate from cassava leaves with crude protein (CP) content ...

Assessment of elimination profile of albendazole residues in fish.

Science.gov (United States)

Busatto, Zenaís; de França, Welliton Gonçalves; Cyrino, José Eurico Possebon; Paschoal, Jonas Augusto Rizzato

2018-01-01

Few drugs are specifically regulated for aquaculture. Thus this study considered albendazole (ABZ) as a potential drug for use in fish, which, however, is not yet regulated for this application. ABZ is a broad-spectrum anthelmintic approved for farmed ruminants and recently considered for treatment of fish parasites. It is the subject of careful monitoring because of potential residues in animal products. This study evaluated the depletion of ABZ and its main known metabolites: albendazole sulfoxide - ABZSO, albendazole sulfone - ABZSO 2 and albendazole amino sulfone - ABZ-2-NH 2 SO 2 , in the fillets of the Neotropical Characin pacu, Piaractus mesopotamicus, which were fed diets containing 10 mg ABZ kg -1 body weight in a single dose. Fish were euthanised at 8, 12, 24, 48, 72, 96 and 120 hours after medication and the depletion profiles of ABZ, each metabolite and the sum of all marker residues were assessed and evaluated taking into account methodological variations regarding determination of the maximum residue limits adopted by different international regulating agencies for estimation of the withdrawal period (WP). The estimated WPs ranged from 2 to 7 days.

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

Science.gov (United States)

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

2017-09-01

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

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

Science.gov (United States)

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

2012-06-01

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

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

Directory of Open Access Journals (Sweden)

Laine J

2016-04-01

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

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

Science.gov (United States)

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

2017-08-01

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

Actinide recovery from pyrochemical residues

International Nuclear Information System (INIS)

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

1984-01-01

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

Actinide recovery from pyrochemical residues

International Nuclear Information System (INIS)

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

1985-05-01

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

Distribution of Animal Drugs among Curd, Whey, and Milk Protein Fractions in Spiked Skim Milk and Whey.

Science.gov (United States)

Shappell, Nancy W; Shelver, Weilin L; Lupton, Sara J; Fanaselle, Wendy; Van Doren, Jane M; Hakk, Heldur

2017-02-01

It is important to understand the partitioning of drugs in processed milk and milk products, when drugs are present in raw milk, in order to estimate the potential consumer exposure. Radioisotopically labeled erythromycin, ivermectin, ketoprofen, oxytetracycline, penicillin G, sulfadimethoxine, and thiabendazole were used to evaluate the distribution of animal drugs among rennet curd, whey, and protein fractions from skim cow milk. Our previous work reported the distribution of these same drugs between skim and fat fractions of milk. Drug distribution between curd and whey was significantly correlated (R 2 = 0.70) to the drug's lipophilicity (log P), with improved correlation using log D (R 2 = 0.95). Distribution of drugs was concentration independent over the range tested (20-2000 nM). With the exception of thiabendazole and ivermectin, more drug was associated with whey protein than casein on a nmol/g protein basis (oxytetracycline experiment not performed). These results provide insights into the distribution of animal drug residues, if present in cow milk, among milk fractions, with possible extrapolation to milk products.

First report of the concentrations and implications of DDT residues in chicken eggs from a malaria-controlled area.

Science.gov (United States)

Bouwman, Hindrik; Bornman, Riana; van Dyk, Cobus; Barnhoorn, Irene

2015-10-01

In malaria-endemic areas, where DDT is still used for vector control by indoor residual spraying (IRS), the concentrations of DDT in human blood and breast milk are high, and there are indications of human health impacts. To identify the possible avenues of exposure reduction, we created the concept of a Total Homestead Environment Approach (THEA). THEA characterizes the interactions between DDT, humans, and the biota within and around homesteads. One dietary route of human exposure and uptake of DDT, namely, chicken egg consumption, has to our knowledge never been studied. The ΣDDT in eggs from a DDT-sprayed village ranged between 5200 and 48,000 ng/g wm (wet mass), with a median of 11,000 ng/g wm. On a lipid mass-basis (lm), the mean ΣDDT for eggs from the sprayed village was 100,000 ng/g lm. The maximum egg concentration observed was three orders of magnitude higher than the median. The acceptable daily intake (ADI) was not exceeded based on the consumption of three eggs per week for a 60 kg person. This equates to an intake of 0.089 g DDT per person per year. Chicken egg consumption is therefore a possible target for exposure reduction, probably best achieved by reducing the DDT concentrations in soils. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2016-02-01

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

Water leaching of titanium from ore flotation residue.

Science.gov (United States)

Jaworska, Malgorzata M; Guibal, Eric

2003-01-01

Copper ore tailings were tested for the stability of titanium submitted to water leaching in three different reactor systems (agitated vessel, bioreactor and percolated fixed-bed column). For each of these systems, titanium extraction did not exceed 1% of the available metal. Biomass removed from ore residue adsorbed a small part of the titanium with sorption capacities below 20-30 mg g(-1), but most of this biomass was sequestered in the ore residue. Oxygen and carbon dioxide concentrations were monitored and changes in concentration correlated with bacteria development at the initial stage of the process and to fungal development in the latter stages.

Pharmaceutical consumption and residuals potentially relevant to nutrient cycling in Greater Accra, Ghana

Directory of Open Access Journals (Sweden)

Evren Sinar

2010-04-01

Full Text Available Recycling nutrients form sanitary wastes back into agricultural ecosystems offers an option to alleviate soil depletion in regions where the use of mineral fertiliser is limited. Exemplary nutrient and water cycling approaches, including collection, treatment and use of human urine, are established at Valley View University (VVU in Greater Accra, Ghana.Concerns have been recently raised in regard to fate and impact of pharmaceutical residues in soils and interlinked environment. To evaluate in how far emerging knowledge can be transposed onto VVU, urban and rural environments in Greater Accra, spatial disease occurrence and drug consumption patterns were studied. Malaria has been found to represent the most severe health burden in Ghana, but there is also a high prevalence of infectious diseases. Drugs consumed in great quantities and in respect to their residual loads potentially problematic in the environment belong to therapeutic groups of: antibiotics, analgesics, drugs for diabetes, antimalarials, cardiovascular drugs and anthelmintics. Drug consumption revealed to be highest in urban and lowest in rural areas. At VVU the range of consumed drugs is comparable to urban areas except for the negligible use of diabetes and cardiovascular medication as well as contraceptives.

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

Science.gov (United States)

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

2017-10-01

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

Evaluation of bi-functionalized mesoporous silicas as reversed phase/cation-exchange mixed-mode sorbents for multi-residue solid phase extraction of veterinary drug residues in meat samples.

Science.gov (United States)

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

2017-04-01

A SBA-15 type mesoporous silica was synthesized and bi-functionalized with octadecylsilane (C18) or octylsilane (C8), and sulfonic acid (SO 3 - ) groups in order to obtain materials with reversed-phase/strong cation-exchange mixed-mode retention mechanism. The resulting hybrid materials (SBA-15-C18-SO 3 - and SBA-15-C8-SO 3 - ) were comprehensively characterized. They showed high surface area, high pore volume and controlled porous size. Elemental analysis of the materials revealed differences in the amount of C18 and C8. SBA-15-C18-SO 3 - contained 0.19mmol/g of C18, while SBA-15-C8-SO 3 - presented 0.54mmol/g of C8. The SO 3 - groups anchored to the silica surface of the pore walls were 0.20 and 0.09mmol/g, respectively. The bi-functionalized materials were evaluated as SPE sorbents for the multi-residue extraction of 26 veterinary drug residues in meat samples using ultra-high-performance liquid chromatography coupled to mass spectrometry detector (UHPLC-MS/MS). Different sorbent amounts (100 and 200mg) and organic solvents were tested to optimize the extraction procedure. Both silicas showed big extraction potential and were successful in the extraction of the target analytes. The mixed-mode retention mechanism was confirmed by comparing both silicas with SBA-15 mesoporous silica mono-functionalized with C18 and C8. Best results were achieved with 200mg of SBA-15-C18-SO 3 - obtaining recoveries higher than 70% for the majority of analytes. Copyright © 2016 Elsevier B.V. All rights reserved.

Environmental interpretation using insoluble residues within reef coral skeletons: problems, pitfalls, and preliminary results

Science.gov (United States)

Budd, Ann F.; Mann, Keith O.; Guzmán, Hector M.

1993-03-01

Insoluble residue concentrations have been measured within colonies of four massive reef corals from seven localities along the Caribbean coast of Panama to determine if detrital sediments, incorporated within the skeletal lattice during growth, record changes in sedimentation over the past twenty years. Amounts of resuspended sediment have increased to varying degrees at the seven localities over the past decades in response to increased deforestation in nearby terrestrial habitats. Preliminary results of correlation and regression analyses reveal few consistent temporal trends in the insoluble residue concentration. Analyses of variance suggest that amounts of insoluble residues, however, differ among environments within species, but that no consistent pattern of variation exists among species. D. strigosa and P. astreoides possess high concentrations at protected localities, S. siderea at localities with high amounts of resuspended sediment, and M. annularis at the least turbid localities. Little correlation exists between insoluble residue concentration and growth band width within species at each locality. Only in two more efficient suspension feeders ( S. siderea and D. strigosa) do weak negative correlations with growth band width exist overall. These results indicate that insoluble residue concentrations cannot be used unequivocally in environmental interpretation, until more is known about tissue damage, polyp behavior, and their effects on the incorporation of insolubles in the skeleton during growth in different coral species. Insoluble residue data are highly variable; therefore, large sample sizes and strong contrasts between environments are required to reveal significant trends.

Modelling of the long-term fate of pesticide residues in agricultural soils and their surface exchange with the atmosphere: Part II. Projected long-term fate of pesticide residues.

Science.gov (United States)

Scholtz, M T; Bidleman, T F

2007-05-01

In the first part of this paper, a simple coupled dynamic soil-atmosphere model for studying the gaseous exchange of pesticide soil residues with the atmosphere is described and evaluated by comparing model results with published measurements of pesticide concentrations in air and soil. In Part II, the model is used to study the concentration profiles of pesticide residues in both undisturbed and annually tilled agricultural soils. Future trends are estimated for the measured air and soil concentrations of lindane and six highly persistent pesticides (toxaphene, p,p'-DDE, dieldrin, cis- and trans-chlordane and trans-nonachlor) over a twenty-year period due to volatilization and leaching into the deeper soil. Wet deposition and particle associated pesticide deposition (that increase soil residue concentrations) and soil erosion, degradation in the soil (other than for lindane) and run-off in precipitation are not considered in this study. Estimates of the rain deposition fluxes are reported that show that, other than for lindane, net volatilization fluxes greatly exceed rain deposition fluxes. The model shows that the persistent pesticides studied are highly immobile in soil and that loss of these highly persistent residues from the soil is by volatilization rather than leaching into the deeper soil. The soil residue levels of these six pesticides are currently sources of net volatilization to the atmosphere and will remain so for many years. The maximum rate of volatilization from the soil was simulated by setting the atmospheric background concentration to zero; these simulations show that the rates of volatilization will not be significantly increased since soil resistance rather than the atmospheric concentration controls the volatilization rates. Annual tilling of the soils increases the volatilization loss to the atmosphere. Nonetheless, the model predicts that, if only air-soil exchange is considered, more than 76% of current persistent pesticide residues

Organochlorine residues in bat guano from nine Mexican caves, 1991

Science.gov (United States)

Clark, D.R.; Moreno-Valdez, A.; Mora, M.A.

1995-01-01

Samples of bat guano, primarily from Mexican free-tailed bats (Tadarida brasiliensis), were collected at nine bat roosts in caves in northern and eastern Mexico and analysed for organochlorine residues. DDE, the most abundant residue found in each cave, was highest (0.99 p.p.m. dry weight) at Ojuela Cave, Durango. Other studies of DDE in bat guano indicate that this concentration is too low to reflect harmful concentrations in the bats themselves. The DDE at Ojuela may represent either lingering residues from use of DDT years ago in the Ojuela area of perhaps depuration loss from migrant bats with summer maternity roost(s) in a DDE-contaminated area such as Carlsbad Cavern, New Mexico. Presence of o,p-DDT at Tio Bartolo Cave, Nuevo Leon, indicates recent use of DDT, but the concentration of this contaminant was low. Possible impacts on bat colonies of the organophosphorus and carbamate insecticides now in extensive use are unknown.

Numerical and Experimental Study on the Residual Stresses in the Nitrided Steel

Science.gov (United States)

Song, X.; Zhang, Zhi-Qian; Narayanaswamy, S.; Huang, Y. Z.; Zarinejad, M.

2016-09-01

In the present work, residual stresses distribution in the gas nitrided AISI 4140 sample has been studied using finite element (FE) simulation. The nitrogen concentration profile is obtained from the diffusion-controlled compound layer growth model, and nitrogen concentration controls the material volume change through phase transformation and lattice interstitials which results in residual stresses. Such model is validated through residual stress measurement technique—micro-ring-core method, which is applied to the nitriding process to obtain the residual stresses profiles in both the compound and diffusion layer. The numerical and experimental results are in good agreement with each other; they both indicate significant stress variation in the compound layer, which was not captured in previous research works due to the resolution limit of the traditional methods.

Chlortetracycline and Oxytetracycline Residues in Poultry Tissues and Eggs

Science.gov (United States)

Meredith, W. E.; Weiser, H. H.; Winter, A. R.

1965-01-01

A pad-plate method of assaying residual amounts of chlortetracycline (CTC) and oxytetracycline (OTC) using Bacillus cereus 213 was used to determine amounts of antibiotic left in tissues and eggs of poultry fed 1,000 and 200 ppm of CTC and OTC in basal feed mixtures. The effects of various methods of cooking the tissues and eggs and the potentiating effect of terephthalic acid (TPA) were studied. It was found that normal methods of roasting, frying, and autoclaving poultry tissue destroyed all residual CTC and OTC, even with the potentiating effect of TPA. The largest amounts of residual antibiotic were found in the liver, then breast, and then thigh tissue when assayed for CTC. Tissue assays for CTC revealed that it was not taken up as extensively as CTC and the largest amounts were found in the liver, then breast. OTC residue was seldom found in the thigh tissue. Terephthalic acid in 0.5% concentration increased the concentration found in all cases. Cooking by poaching and scrambling eggs did not destroy the antibiotic in all cases. PMID:14264853

Determination of Pesticides Residues in Cucumbers Grown in Greenhouse and the Effect of Some Procedures on Their Residues.

Science.gov (United States)

Leili, Mostafa; Pirmoghani, Amin; Samadi, Mohammad Taghi; Shokoohi, Reza; Roshanaei, Ghodratollah; Poormohammadi, Ali

2016-11-01

The objective of this study was to determine the residual concentrations of ethion and imidacloprid in cucumbers grown in greenhouse. The effect of some simple processing procedures on both ethion and imidacloprid residues were also studied. Ten active greenhouses that produce cucumber were randomly selected. Ethion and imidacloprid as the most widely used pesticides were measured in cucumber samples of studied greenhouses. Moreover, the effect of storing, washing, and peeling as simple processing procedures on both ethion and imidacloprid residues were investigated. One hour after pesticide application; the maximum residue levels (MRLs) of ethion and imidacloprid were higher than that of Codex standard level. One day after pesticide application, the levels of pesticides were decreased about 35 and 31% for ethion and imidacloprid, respectively, which still were higher than the MRL. Washing procedure led to about 51 and 42.5% loss in ethion and imidacloprid residues, respectively. Peeling procedure also led to highest loss of 93.4 and 63.7% in ethion and imidacloprid residues, respectively. The recovery for both target analytes was in the range between 88 and 102%. The residue values in collected samples one hour after pesticides application were higher than standard value. The storing, washing, and peeling procedures lead to the decrease of pesticide residues in greenhouse cucumbers. Among them, the peeling procedure has the greatest impact on residual reduction. Therefore, these procedures can be used as simple and effective processing techniques for reducing and removing pesticides from greenhouse products before their consumption.

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

DEFF Research Database (Denmark)

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

2010-01-01

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

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

Energy Technology Data Exchange (ETDEWEB)

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

2016-01-15

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

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

Science.gov (United States)

2010-08-03

... drug substance than what is intended to be delivered to the patient. This excess amount of drug... issue not only to the patient, but also to others including family members, caregivers, children, and...

Laboratory studies of the properties of in-situ burn residues: chemical composition of residues

International Nuclear Information System (INIS)

Trudel, B.K.; Buist, I.A.; Schatzke, D.; Aurand, D.

1996-01-01

The chemical composition of the residue from small-scale burns of thick oil slicks was studied. The objective was to describe the changes in chemical composition in oils burning on water and to determine how these changes were influenced by the condition of the burn. Small-scale test burns involved burning 40-cm diameter pools of oil on water. A range of eight oil types including seven crude oils and an automotive diesel were burned. For each oil, slicks of fresh oil of three different thicknesses were tested. Two of the oils were tested before and after weathering. Results showed that the composition of the residue differed greatly from the parent oil. Asphaltenes, high-boiling-point aromatics and resins remained concentrated in the burn residue. The burning of slicks appeared to remove most of the lower-molecular weight aromatic hydrocarbons which included the more toxic and more bioavailable components of the crude oils. 11 refs., 6 tabs

Determination of Oxytetracycline and 4-Epi-Oxytetracycline Residues in Feathers and Edible Tissues of Broiler Chickens Using Liquid Chromatography Coupled with Tandem Mass Spectrometry.

Science.gov (United States)

Cornejo, Javiera; Pokrant, Ekaterina; Krogh, Magdalena; Briceño, Cristóbal; Hidalgo, Héctor; Maddaleno, Aldo; Araya-Jordán, Carolina; Martín, Betty San

2017-04-01

Antibiotics have been widely used in poultry production for the treatment of bacterial diseases. However, drug residues can remain in products derived from animals after the cessation of the drug therapies. Feathers, in particular, have shown an affinity for antibiotics such as tetracycline, suggesting the persistence of these drugs in nonedible tissue. After the birds are slaughtered, feathers are ground into feather meals, which are used as organic fertilizer or an ingredient in animal diets, thereby entering into the food chain and becoming a potential risk for public health. To evaluate the depletion of oxytetracycline (OTC) and its metabolite 4-epi-oxytetracycline (4-epi-OTC) in the muscles, liver, and feathers, 64 broiler chickens, bred under controlled conditions, were treated orally with a commercial formulation of 10% OTC for 7 days. The analytes were quantified using liquid chromatography-tandem mass spectrometry. OTC and 4-epi-OTC were found in the feathers for 46 days, whereas they were found in the muscle and liver for only 12 and 6 days, respectively. These results prove that the analytes remain in feathers in higher concentrations than they do in edible tissues after treatment with tetracyclines. Thus, feather meals represent a potential source of antimicrobial residue contamination in the food chain.

A new application of micellar liquid chromatography in the determination of free ampicillin concentration in the drug-human serum albumin standard solution in comparison with the adsorption method.

Science.gov (United States)

Stępnik, Katarzyna E; Malinowska, Irena; Maciejewska, Małgorzata

2016-06-01

The determination of free drug concentration is a very important issue in the field of pharmacology because only the unbound drug fraction can achieve a pharmacological effect. Due to the ability to solubilize many different compounds in micellar aggregates, micellar liquid chromatography (MLC) can be used for direct determination of free drug concentration. Proteins are not retained on the stationary phase probably due to the formation of protein - surfactant complexes which are excluded from the pores of stationary phase. The micellar method is simple and fast. It does not require any pre-preparation of the tested samples for analysis. The main aim of this paper is to demonstrate a completely new applicability of the analytical use of MLC concerning the determination of free drug concentration in the standard solution of human serum albumin. The well-known adsorption method using RP-HPLC and the spectrophotometric technique was applied as the reference method. The results show that the free drug concentration value obtained in the MLC system (based on the RP-8 stationary phase and CTAB) is similar to that obtained by the adsorption method: both RP-HPLC (95.83μgmL(-1), 79.86% of free form) and spectrophotometry (95.71μgmL(-1), 79.76%). In the MLC the free drug concentration was 93.98μgmL(-1) (78.3%). This indicates that the obtained results are within the analytical range of % of free ampicillin fraction and the MLC with direct sample injection can be treated like a promising method for the determination of free drug concentration. Copyright © 2016 Elsevier B.V. All rights reserved.

Impacts of channel morphology on residues and ecological risks of polychlorinated biphenyls in water and sediment in Chahe River

Directory of Open Access Journals (Sweden)

Zhen-hua Zhao

2016-10-01

Full Text Available The impacts of channel morphology on the residues and ecological risks of 14 polychlorinated biphenyl (PCB congeners in water and sediment were investigated in summer (July and autumn (September in the Chahe River, in Nanjing, China. The residual concentrations of tri-chlorobiphenyls (tri-CBs, PCB 18 and tetra-CBs (PCB 52 in water were significantly higher than those of penta-CBs to deca-CBs, and the average residual concentration of ∑PCBs (sum of 14 PCB congeners in summer was about six times higher than in autumn. However, the residues in sediment did not change significantly. Redundancy analysis (RDA indicated that channel morphology and the corresponding environmental indices had significant impacts on PCB residues and their composition profiles in water and sediment. The overflow weir and lake-type watercourse may remarkably reduce the residual concentration and ecological risks of PCBs in water. The highest reduction percentages of the residual concentration and ecological risks of ∑PCBs induced by an overflow weir were 78% and 67%, respectively, and those induced by a lake-type watercourse were 36% and 70%, respectively. The watercourses with different channel morphologies were ranked by residual ∑PCBs concentrations in the following descending order: the natural ecological watercourse, vertical concrete watercourse, and vegetation-type riprap watercourse. However, they were ranked by residual ∑PCBs concentrations in sediment in the following descending order: the vertical concrete watercourse, vegetation-type riprap watercourse, and natural ecological watercourse.

Residual cannabis levels in blood, urine and oral fluid following heavy cannabis use.

Science.gov (United States)

Odell, Morris S; Frei, Matthew Y; Gerostamoulos, Dimitri; Chu, Mark; Lubman, Dan I

2015-04-01

An understanding of tetrahydrocannabinol (THC) kinetics and residual levels after cannabis use is essential in interpreting toxicology tests in body fluids from live subjects, particularly when used in forensic settings for drug abuse, traffic and interpersonal violence cases. However the current literature is largely based on laboratory studies using controlled cannabis dosages in experienced users, with limited research investigating the kinetics of residual THC concentrations in regular high dose cannabis users. Twenty-one dependent cannabis users were recruited at admission to two residential detoxification units in Melbourne, Australia. After being provided with information about, and consenting to, the study, subjects volunteered to provide once-daily blood, urine and oral fluid (saliva) samples for seven consecutive days following admission, involving cessation and abstinence from all cannabis use. Blood and oral fluid specimens were analysed for THC and urine specimens for the metabolite THC-COOH. In some subjects THC was detectable in blood for at least 7 days and oral fluid specimens were positive for THC up to 78 h after admission to the unit. Urinary THC-COOH concentrations exceeded 1000 ng/mL for some subjects 129 h after last use. The presented blood THC levels are higher and persist longer in some individuals than previously described, our understanding and interpretation of THC levels in long term heavy cannabis users may need to be reconsidered. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Drug-Target Kinetics in Drug Discovery.

Science.gov (United States)

Tonge, Peter J

2018-01-17

The development of therapies for the treatment of neurological cancer faces a number of major challenges including the synthesis of small molecule agents that can penetrate the blood-brain barrier (BBB). Given the likelihood that in many cases drug exposure will be lower in the CNS than in systemic circulation, it follows that strategies should be employed that can sustain target engagement at low drug concentration. Time dependent target occupancy is a function of both the drug and target concentration as well as the thermodynamic and kinetic parameters that describe the binding reaction coordinate, and sustained target occupancy can be achieved through structural modifications that increase target (re)binding and/or that decrease the rate of drug dissociation. The discovery and deployment of compounds with optimized kinetic effects requires information on the structure-kinetic relationships that modulate the kinetics of binding, and the molecular factors that control the translation of drug-target kinetics to time-dependent drug activity in the disease state. This Review first introduces the potential benefits of drug-target kinetics, such as the ability to delineate both thermodynamic and kinetic selectivity, and then describes factors, such as target vulnerability, that impact the utility of kinetic selectivity. The Review concludes with a description of a mechanistic PK/PD model that integrates drug-target kinetics into predictions of drug activity.

A manual for implementing residual radioactive material guidelines

International Nuclear Information System (INIS)

Gilbert, T.L.; Yu, C.; Yuan, Y.C.; Zielen, A.J.; Jusko, M.J.; Wallo, A. III; Argonne National Lab., IL; Dames and Moore, West Valley, NY; Argonne National Lab., IL; USDOE Assistant Secretary for Nuclear Energy, Washington, DC

1989-06-01

This manual presents information for implementing US Department of Energy (DOE) guidelines for residual radioactive material at sites identified by the Formerly Utilized Sites Remedial Action Program (FUSRAP) and the Surplus Facilities Management Program (SFMP). It describes the analysis and models used to derive site-specific guidelines for allowable residual concentrations of radionuclides in soil and the design and use of the RESRAD computer code for calculating guideline values. It also describes procedures for implementing DOE policy for reducing residual radioactivity to levels that are as low as reasonably achievable. 36 refs., 16 figs, 22 tabs

Development of irradiation technique on controlling food contamination residue

International Nuclear Information System (INIS)

Liu Bin; Xiong Shanbai; Xiong Guangquan; Cheng Wei; Chen Yuxia; Liao Tao; Li Xin; Lin Ruotai

2010-01-01

The current state of the researches of irradiation technology on controlling food mycotoxin, pesticide, veterinary drugs and fishery drugs residue was summarized. And the degradation rate, mechanism, products and toxicities of food contamination were expatiated. The free radical from irradiation attack the site of weaker bond, and the less or more toxic substances were produced, which lead to the degradation of the food contamination. The limitations and future application of irradiation technique on controlling food contamination were also analyzed. (authors)

Residues of Organochlorinated Pesticides in Soil from Tomato ...

African Journals Online (AJOL)

This work presents the concentrations of five pesticide residues, lindane, chlorpyrifos, endosulfan, p, p'-DDE and p, p'-DDD in soil samples collected from tomato fields in Ngarenanyuki, Tanzania. Endosulfan sulphate was detected in 100 % of the sample analysed with mean concentration of 0.2407 mg/kg dw. Chlorpyrifos ...

Influence of organic waste and residue mud additions on chemical, physical and microbial properties of bauxite residue sand.

Science.gov (United States)

Jones, Benjamin E H; Haynes, Richard J; Phillips, Ian R

2011-02-01

In an alumina refinery, bauxite ore is treated with sodium hydroxide at high temperatures and pressures and for every tone of alumina produced, about 2 tones of alkaline, saline bauxite processing waste is also produced. At Alcoa, a dry stacking system of disposal is used, and it is the sand fraction of the processing waste that is rehabilitated. There is little information available regarding the most appropriate amendments to add to the processing sand to aid in revegetation. The purpose of this study was to investigate how the addition of organic wastes (biosolids and poultry manure), in the presence or absence of added residue mud, would affect the properties of the residue sand and its suitability for revegetation. Samples of freshly deposited residue sand were collected from Alcoa's Kwinana refinery. Samples were treated with phosphogypsum (2% v/v), incubated, and leached. A laboratory experiment was then set up in which the two organic wastes were applied at 0 or the equivalent to 60 tones ha(-1) in combination with residue mud added at rates of 0%, 10% and 20% v/v. Samples were incubated for 8 weeks, after which, key chemical, physical and microbial properties of the residue sand were measured along with seed germination. Additions of residue mud increased exchangeable Na(+), ESP and the pH, and HCO (3) (-) and Na(+) concentrations in saturation paste extracts. Additions of biosolids and poultry manure increased concentrations of extractable P, NH (4) (+) , K, Mg, Cu, Zn, Mn and Fe. Addition of residue mud, in combination with organic wastes, caused a marked decrease in macroporosity and a concomitant increase in mesoporosity, available water holding capacity and the quantity of water held at field capacity. With increasing residue mud additions, the percentage of sample present as sand particles (2 mm diameter) increased; greatest aggregation occurred where a combination of residue mud and poultry manure were added. Stability of aggregates, as measured by

The difficulties for a photolabile drug in topical formulations: the case of diclofenac.

Science.gov (United States)

Ioele, Giuseppina; De Luca, Michele; Tavano, Lorena; Ragno, Gaetano

2014-04-25

Topical commercial formulations containing diclofenac (DC) were submitted to photostability tests, according to the international rules, showing a clear degradation of the drug. The degradation process was monitored by applying the multivariate curve resolution technique to the UV spectral data from samples exposed to stressing irradiation. This method was able to estimate the number of components evolved as well as to draw their spectra and concentration profiles. Three photoproducts (PhPs) were resolved by the analysis of photodegradation kinetics, according to two consecutive reactions with a mechanism postulated as DC>PhP₁>PhP₂ and PhP₃. Photodegradation rate of DC in gel was found to be very fast, with a residual content of 90% only after 3.90 min under a radiant exposure of 450 Wm(-2). Because of a very slow skin uptake of DC, a prolonged time of exposure to light could lead to a significant decrease of drug available or the uptake of undesired photoproducts. New gel formulations were designed to increase the photostability of DC by incorporating chemical light-absorbers or entrapping the drug into cyclodextrin. Drug photostability resulted increased significantly in comparison with that of the commercial formulations. The gel containing the light-absorbers such as octisilate, octyl methoxycinnamate and a combination thereof showed a residual DC of 90% up to 12.22 min, 13.75 min and 15.71 min, respectively, under the same irradiation power. The best results were obtained by incorporating the drug in β-cyclodextrin with a degradation of 10% after 25.01 min of light exposure. Copyright © 2014 Elsevier B.V. All rights reserved.

Residual nilpotence and residual solubility of groups

International Nuclear Information System (INIS)

Mikhailov, R V

2005-01-01

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

Environmental toxicity and radioactivity assessment of a titanium-processing residue with potential for environmental use.

Science.gov (United States)

Wendling, Laura A; Binet, Monique T; Yuan, Zheng; Gissi, Francesca; Koppel, Darren J; Adams, Merrin S

2013-07-01

Thorough examination of the physicochemical characteristics of a Ti-processing residue was undertaken, including mineralogical, geochemical, and radiochemical characterization, and an investigation of the environmental toxicity of soft-water leachate generated from the residue. Concentrations of most metals measured in the leachate were low; thus, the residue is unlikely to leach high levels of potentially toxic elements on exposure to low-ionic strength natural waters. Relative to stringent ecosystem health-based guidelines, only chromium concentrations in the leachate exceeded guideline concentrations for 95% species protection; however, sulfate was present at concentrations known to cause toxicity. It is likely that the high concentration of calcium and extreme water hardness of the leachate reduced the bioavailability of some elements. Geochemical modeling of the leachate indicated that calcium and sulfate concentrations were largely controlled by gypsum mineral dissolution. The leachate was not toxic to the microalga Chlorella sp., the cladoceran Ceriodaphnia dubia, or the estuarine bacterium Vibrio fischeri. The Ti-processing residue exhibited an absorbed dose rate of 186 nGy/h, equivalent to an annual dose of 1.63 mGy and an annual effective dose of 0.326 mGy. In summary, the results indicate that the Ti-processing residue examined is suitable for productive use as an environmental amendment following 10 to 100 times dilution to ameliorate potential toxic effects due to chromium or sulfate. Copyright © 2013 SETAC.

Differential residual effects of zaleplon and zopiclone on actual driving: a comparison with a low dose of alcohol.

Science.gov (United States)

Vermeeren, Annemiek; Riedel, Wim J; van Boxtel, Martin P J; Darwish, Mona; Paty, Isabelle; Patat, Alain

2002-03-15

To compare residual effects of zaleplon 10 mg, zopiclone 7.5 mg, and placebo, and a social dose of alcohol on car driving, memory, and psychomotor performance. Two-part placebo controlled, crossover study. Part 1 was single blind, Part 2 double blind. University research institute. Thirty healthy volunteers (15 men and 15 women, mean age 32 +/- 7 years) In Part 1 alcohol and alcohol-placebo drinks were administered around noon. In Part 2 single oral doses of zaleplon 10 mg, zopiclone 7.5 mg and placebo were administered at bedtime. A highway driving test, laboratory tests of word learning, critical tracking and divided attention, and subjective assessments of sleep, mood, and effects of treatments on driving. Driving started 40 minutes after a second alcohol dose in Part 1, and 10 hours after drug intake in Part 2. The results demonstrated that alcohol, at average plasma concentrations of approximately 0.030 g/dl, significantly impaired performance in all tests. Zaleplon's residual effects did not differ significantly from those of placebo in any test. In contrast, zopiclone had significant residual effects on driving, divided attention, and memory. The magnitude of impairment in the driving test observed the morning after zopiclone 7.5 mg was twice that observed with alcohol. Zaleplon 10 mg has no residual effects on driving when taken at bedtime, 10 hours before driving. In contrast, zopiclone 7.5 mg can cause marked residual impairment. Patients should be advised to avoid driving the morning after zopiclone administration.

Removal of heavy metals from aqueous solution by Carrot residues

International Nuclear Information System (INIS)

Eslamzadeh, T.; Nasernejad, B.; Bonakdar Pour, B.; Zamani, A.; Esmaail-Beygi, M.

2004-01-01

The removal of Copper(II), Zinc(II), and Chromium (III) from wastewater by carrot residues was investigated to evaluate cation exchange capacity. The effects of solution P H and co-ions were studied in batch experiments. Adsorption equilibria were initially rapidly established, and then decreased markedly after 10 min. Column experiments were carried out in a glass column filled with carrot residues to evaluate the metal removal capacity. The influences of the feed concentration and feed rate were also studied in order to compare the dynamic capacity for metal binding in different feed concentrations

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

Science.gov (United States)

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

2015-11-01

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

Organochlorine residues in harp seals, Phoca groenlandica, from the Gulf of St. Lawrence and Hudson Strait: An evaluation of contaminant concentrations and burdens

Energy Technology Data Exchange (ETDEWEB)

Beck, G.G.; Smith, T.G. (Dept. of Fisheries and Oceans, Nanaimo, BC (Canada)); Addison, R.F. (Dept. of Fisheries and Oceans, Sidney, BC (Canada))

1994-01-01

Organochlorine contaminant concentrations and burdens were evaluated in blubber samples from 50 harp seals (Phoca groenlandica) obtained from the estuary and northern Gulf of St. Lawrence and Hudson Strait, Canada between December 1988 and December 1989. The concentration and burden of polychlorinated biphenyls (PCBs) increased significantly during the winter months for males occupying the St. Lawrence estuary. The potential for rapid accumulation of contaminants in the estuary was also observed among females: nine postpartum females (1 month after weaning) had higher organochlorine levels than prepartum females from the same location. The lowest observed contaminant concentrations and burdens were in seals from Hudson Strait in autumn. In winter specimens, males had DDT and PCB concentrations about 4 and 2 times as great, respectively, as females of similar age distribution and collection date. Congeners with IUPAC Nos. 138 and 153 accounted for more than 50% of total identifiable PCBs, which is consistent with their prevalence in other marine biota. The concentration of PCBs has declined and the percent p,p'-DDE of total DDT has increased between 1982 and the present study. Unlike the beluga whale (Delphinapterus leucas), harp seals occupy the more polluted waters of the estuary only seasonally, and this may account for their lower residue concentrations. 59 refs., 1 fig., 5 tabs.

Obtention of ceramic pigments with residue from electroplating

International Nuclear Information System (INIS)

Boss, A.; Kniess, C.T.; Aguiar, B.M. de; Prates, P.B.; Milanez, K.

2011-01-01

The incorporation of industrial residues in industrial processes opens up new business opportunities and reduces the volume of extraction of raw materials, preserving natural resources, which are limited. An important residue is the mud from galvanic industry, consisting of alkali and transition metals. According to NBR 10004/2004, this residue can be classified as Class I (hazardous), depending on the concentration of metals present in the mud. This paper proposes a method for reusing the residue from electroplating in ceramic pigments. The characterization of residual plating was obtained by chemical analysis, mineralogical analysis and pH measurements. The electroplating waste was incorporated in different percentages on a standard pigment formula of industrial ceramic, consisting mainly of Zn, Fe and Cr. The obtained pigments were applied in ceramic glazes to colorimetric and visual analysis, which showed good results with the addition of up to 15% of industrial waste. (author)

Residual Isocyanates in Medical Devices and Products: A Qualitative and Quantitative Assessment

Directory of Open Access Journals (Sweden)

Gillian Franklin

2016-01-01

Full Text Available We conducted a pilot qualitative and quantitative assessment of residual isocyanates and their potential initial exposures in neonates, as little is known about their contact effect. After a neonatal intensive care unit (NICU stockroom inventory, polyurethane (PU and PU foam (PUF devices and products were qualitatively evaluated for residual isocyanates using Surface SWYPE ™ . Those containing isocyanates were quantitatively tested for methylene diphenyl diisocyanate (MDI species, using UPLC-UV-MS/MS method. Ten of 37 products and devices tested, indicated both free and bound residual surface isocyanates; PU/PUF pieces contained aromatic isocyanates; one product contained aliphatic isocyanates. Overall, quantified mean MDI concentrations were low (4,4‘-MDI = 0.52 to 140.1 pg/mg and (2,4‘-MDI = 0.01 to 4.48 pg/mg. The 4,4‘-MDI species had the highest measured concentration (280 pg/mg. Commonly used medical devices/products contain low, but measurable concentrations of residual isocyanates. Quantifying other isocyanate species and neonatal skin exposure to isocyanates from these devices and products requires further investigation.

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

Science.gov (United States)

Ayoub, Bassam M

2017-07-01

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

Addition of an organic amendment and/or residue mud to bauxite residue sand in order to improve its properties as a growth medium.

Science.gov (United States)

Jones, B E H; Haynes, R J; Phillips, I R

2012-03-01

The effects of addition of carbonated residue mud (RMC) or seawater neutralized residue mud (RMS), at two rates, in the presence or absence of added green waste compost, on the chemical, physical and microbial properties of gypsum-treated bauxite residue sand were studied in a laboratory incubation study. The growth of two species commonly used in revegetation of residue sand (Lolium rigidum and Acacia saligna) in the treatments was then studied in a 18-week greenhouse study. Addition of green waste-based compost increased ammonium acetate-extractable (exchangeable) Mg, K and Na. Addition of residue mud at 5 and 10% w/w reduced exchangeable Ca but increased that of Mg and Na (and K for RMS). Concentrations of K, Na, Mg and level of EC in saturation paste extracts were increased by residue mud additions. Concentrations of cations in water extracts were considerably higher than those in saturation paste extracts but trends with treatment were broadly similar. Addition of both compost and residue mud caused a significant decrease in macroporosity with a concomitant increase in mesoporosity and microporosity, available water holding capacity and the quantity of water held at field capacity. Increasing rates of added residue mud reduced the percentage of sample present as discrete sand particles and increased that in aggregated form (particularly in the 1-2 and >10mm diameter ranges). Organic C content, C/N ratio, soluble organic C, microbial biomass C and basal respiration were increased by compost additions. Where compost was added, residue mud additions caused a substantial increase in microbial biomass and basal respiration. L. rigidum grew satisfactorily in all treatments although yields tended to be reduced by additions of mud (especially RMC) particularly in the absence of added compost. Growth of A. saligna was poor in sand alone and mud-amended sand and was greatly promoted by additions of compost. However, in the presence of compost, addition of carbonated

A Systematic Study of Molecular Interactions of Anionic Drugs with a Dimethylaminoethyl Methacrylate Copolymer Regarding Solubility Enhancement.

Science.gov (United States)

Saal, Wiebke; Ross, Alfred; Wyttenbach, Nicole; Alsenz, Jochem; Kuentz, Martin

2017-04-03

The methacrylate-copolymer Eudragit EPO (EPO) has raised interest in solubility enhancement of anionic drugs. Effects on aqueous drug solubility at rather low polymer concentrations are barely known despite their importance upon dissolution and dilution of oral dosage forms. We provide evidence for substantial enhancement (factor 4-230) of aqueous solubility of poorly water-soluble anionic drugs induced by low (0.1-5% (w/w)) concentration of EPO for a panel of seven acidic crystalline drugs. Diffusion data (determined by 1 H nuclear magnetic resonance spectroscopy) indicate that the solubility increasing effect monitored by quantitative ultraperformance liquid chromatography was caused primarily by molecular API polymer interactions in the bulk liquid phase. Residual solid API remained unaltered as tested by X-ray powder diffraction. The solubility enhancement (SE) revealed a significant rank correlation (r Spearman = -0.83) with rDiff API , where SE and rDiff API are defined ratios of solubility and diffusion coefficient in the presence and absence of EPO. SE decreased in the order of indomethacin, mefenamic acid, warfarin, piroxicam, furosemide, bezafibrate, and tolbutamide. The solubilizing effect was attributed to both ionic and hydrophobic interactions between drugs and EPO. The excellent solubilizing properties of EPO are highly promising for pharmaceutical development, and the data set provides first steps toward an understanding of drug-excipient interaction mechanisms.

Analysis and characterization of plutonium in pyrochemical salt residues

International Nuclear Information System (INIS)

Haschke, John M.; Phillips, Alan G.

2000-01-01

Quantitative measurement of hydrogen produced during salt-catalyzed hydrolysis of plutonium in pyrochemical salt residues show that the metal is present in concentrations of 10 ± 5 mass%. The analytical method is based on stoichiometric reaction of metal with water to form plutonium monoxide monohydride (PuOH) and hydrogen. Results of a kinetic model developed to describe the observed time dependence of the hydrolysis rate shows that metal is present predominately as particles with essentially spherical geometries and diameters near 1 mm. The presence of smaller metallic particles cannot be verified or excluded. Plutonium concentrations measured for residues stored in different configurations suggest that a sizable fraction of the metal has oxidized during storage. Application of the hydrolysis method in determining concentrations and dimensions of metallic plutonium in other nuclear waste forms is proposed

Evaluation of a Method for Quantifying Eugenol Concentrations in the Fillet Tissue from Freshwater Fish Species.

Science.gov (United States)

Meinertz, Jeffery R; Schreier, Theresa M; Porcher, Scott T; Smerud, Justin R

2016-01-01

AQUI-S 20E(®) (active ingredient, eugenol; AQUI-S New Zealand Ltd, Lower Hutt, New Zealand) is being pursued for approval as an immediate-release sedative in the United States. A validated method to quantify the primary residue (the marker residue) in fillet tissue from AQUI-S 20E-exposed fish was needed. A method was evaluated for determining concentrations of the AQUI-S 20E marker residue, eugenol, in freshwater fish fillet tissue. Method accuracies from fillet tissue fortified at nominal concentrations of 0.15, 1, and 60 μg/g from six fish species ranged from 88-102%. Within-day and between-day method precisions (% CV) from the fortified tissue were ≤8.4% CV. There were no coextracted compounds from the control fillet tissue of seven fish species that interfered with eugenol analyses. Six compounds used as aquaculture drugs did not interfere with eugenol analyses. The lower limit of quantitation (LLOQ) was 0.012 μg/g. The method was robust, i.e., in most cases, minor changes to the method did not impact method performance. Eugenol was stable in acetonitrile-water (3 + 7, v/v) for at least 14 days, in fillet tissue extracts for 4 days, and in fillet tissue stored at ~ -80°C for at least 84 days.

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

Science.gov (United States)

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

Antimicrobial potential of two traditional herbometallic drugs against certain pathogenic microbial species.

Science.gov (United States)

Wijenayake, A U; Abayasekara, C L; Pitawala, H M T G A; Bandara, B M R

2016-09-15

Mineral based preparations are widely used for centuries as antimicrobial agents. However, the efficacy and the mode of action of mineral based preparations are uncertain due to the insufficient antimicrobial studies. Arogyawardhana Vati (AV) and Manikya Rasa (MR) are such two Rasashastra herbo-minerallic drugs commonly in India and other countries in South Asia. Despite of their well known traditional use of skin diseases, reported antimicrobial and mineralogical studies are limited. Therefore, in this study antimicrobial activities of the drugs and their organic, inorganic fractions were evaluated against Pseudomonas aeruginosa, Escherischia coli, Staphylococcus aureus, Methecilline Resistance Staphylococcus aureus - MRSA and Candida albicans. Antimicrobial activity of the drugs, their inorganic residues and organic extracts were determined using four assay techniques viz agar well diffusion, modified well diffusion, Miles and Misra viable cell counting and broth turbidity measurements. Mineralogical constituents of the drugs were determined using X-ray diffraction, while total cation constituents and water soluble cation constituents were determined using inductively coupled plasma-mass spectrometer and the atomic absorption spectrophotometer respectively. Thermogravimetric analysis was used to determine the weight percentages of organic and inorganic fraction of the drugs. Particle sizes of the drugs were determined using the particle size analyzer. AV and MR drugs showed antibacterial activity against both gram positive and gram negative bacterial species when analyzed separately. Inorganic residues of the drugs and organic extracts showed activity at least against two or more bacterial species tested. All tested components were inactive against C. albicans. Common mineral constituents of drugs are cinnabar, biotite and Fe-rich phases. Drugs were rich in essential elements such as Na, K, Ca, Mg and Fe and toxic elements such as Zn, Cu and As. However, the

Influence of turkey meat on residual nitrite in cured meat products.

Science.gov (United States)

Kilic, B; Cassens, R G; Borchert, L L

2001-02-01

A response surface experimental design was employed to estimate residual nitrite level at various initial nitrite concentrations, percent turkey meat in the formula, and heat quantity (F) values using a typical wiener as the test system. Pork and mechanically separated turkey were used as the meat ingredients. Residual nitrite and pH were measured at day 1, 7 days, 14 days, and 49 days after processing. Protein, fat, salt, moisture, and CIE (L*a*b*) color values were also determined. Results showed that the effect of turkey meat on residual nitrite level was significant (P meat in the formula resulted in lower residual nitrite levels at a fixed pH. The residual nitrite level was initially proportional to initial nitrite concentration, but it became a nonsignificant factor during longer storage time. Differences in heat quantity had a significant effect (P nitrite level initially. Greater heat quantity decreased residual nitrite level in finished cured meat products at a fixed pH. However, this effect became nonsignificant during longer storage. Reduction of residual nitrite in wieners because of turkey meat addition at a fixed pH was due to characteristics of the turkey tissue, but the mechanism of action remains unknown. It was also established that commercial wieners had a higher pH if poultry meat was included in the formulation.

Bound xenobiotic residues in food commodities of plant and animal origin: IUPAC Reports on Pesticides (40)

NARCIS (Netherlands)

Skidmore, M.W.; Paulson, G.D.; Kuiper, H.A.; Ohlin, B.

1998-01-01

In order to assess the dietary risk resulting from the use of pesticides or veterinary drugs the nature of the chemical residues on food commodities needs to be determined. Elucidation of the nature of the chemical residue is carried out using radiolabelled studies where the radiolabelled xenobiotic

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

Science.gov (United States)

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

2012-03-01

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

Leaching Behavior of Circulating Fluidised Bed MSWI Air Pollution Control Residue in Washing Process

Directory of Open Access Journals (Sweden)

Zhiliang Chen

2016-09-01

Full Text Available In this study, air pollution control (APC residue is conducted with water washing process to reduce its chloride content. A novel electrical conductivily (EC measurement method is proposed to monitor the dynamic change of chloride concentrations in leachate as well as the chloride content of the residue. The method equally applies to various washing processes with different washing time, liquid/solid ratio and washing frequency. The results show that washing effectively extracts chloride salts from APC residues, including those from circulating fluidized bed (CFB municipal solid waste incineration (MSWI. The most appropriate liquid/solid ratio and washing time in the first washing are found to be around 4 L water per kg of APC residue and 30 min, respectively, and washing twice is required to obtain maximum dissolution. The pH value is the major controlling factor of the heavy metals speciation in leachate, while chloride concentration also affects the speciation of Cd. Water washing causes no perceptible transfer of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs from the APC residue to leachate. The chloride concentration is strongly related with electrical conductivity (EC, as well as with the concentrations of calcium, sodium and potassium of washing water. Their regression analyses specify that soluble chloride salts and EC could act as an indirect indicator to monitor the change of chloride concentration and remaining chloride content, thus, contributing to the selection of the optimal washing conditions.

Residue pattern of polycyclic aromatic hydrocarbons during green tea manufacturing and their transfer rates during tea brewing.

Science.gov (United States)

Gao, Guanwei; Chen, Hongping; Liu, Pingxiang; Hao, Zhenxia; Ma, Guicen; Chai, Yunfeng; Wang, Chen; Lu, Chengyin

2017-06-01

Residues of polycyclic aromatic hydrocarbons (PAHs) in green tea and tea infusion were determined using gas chromatography-tandem mass spectrometry to study their dissipation pattern during green tea processing and infusion. Concentration and evaporation of PAHs during tea processing were the key factors affecting PAH residue content in product intermediates and in green tea. PAH residues in tea leaves increased by 2.4-3.1 times during the manufacture of green tea using the electric heating model. After correction to dry weight, PAH residue concentrations decreased by 33.5-48.4% during green tea processing because of PAH evaporation. Moreover, spreading and drying reduced PAH concentrations. The transfer rates of PAH residues from green tea to infusion varied from 4.6% to 7.2%, and PAH leaching was higher in the first infusion than in the second infusion. These results are useful for assessing exposure to PAHs from green tea and in formulating controls for the maximum residue level of PAHs in green tea.

Gas composition of sludge residue profiles in a sludge treatment reed bed between loadings.

Science.gov (United States)

Larsen, Julie D; Nielsen, Steen M; Scheutz, Charlotte

2017-11-01

Treatment of sludge in sludge treatment reed bed systems includes dewatering and mineralization. The mineralization process, which is driven by microorganisms, produces different gas species as by-products. The pore space composition of the gas species provides useful information on the biological processes occurring in the sludge residue. In this study, we measured the change in composition of gas species in the pore space at different depth levels in vertical sludge residue profiles during a resting period of 32 days. The gas composition of the pore space in the sludge residue changed during the resting period. As the resting period proceeded, atmospheric air re-entered the pore space at all depth levels. The methane (CH 4 ) concentration was at its highest during the first part of the resting period, and then declined as the sludge residue became more dewatered and thereby aerated. In the pore space, the concentration of CH 4 often exceeded the concentration of carbon dioxide (CO 2 ). However, the total emission of CO 2 from the surface of the sludge residue exceeded the total emission of CH 4 , suggesting that CO 2 was mainly produced in the layer of newly applied sludge and/or that CO 2 was emitted from the sludge residue more readily compared to CH 4 .

Role of drug transporters and drug accumulation in the temporal acquisition of drug resistance

International Nuclear Information System (INIS)

Hembruff, Stacey L; Laberge, Monique L; Villeneuve, David J; Guo, Baoqing; Veitch, Zachary; Cecchetto, Melanie; Parissenti, Amadeo M

2008-01-01

Anthracyclines and taxanes are commonly used in the treatment of breast cancer. However, tumor resistance to these drugs often develops, possibly due to overexpression of drug transporters. It remains unclear whether drug resistance in vitro occurs at clinically relevant doses of chemotherapy drugs and whether both the onset and magnitude of drug resistance can be temporally and causally correlated with the enhanced expression and activity of specific drug transporters. To address these issues, MCF-7 cells were selected for survival in increasing concentrations of doxorubicin (MCF-7 DOX-2 ), epirubicin (MCF-7 EPI ), paclitaxel (MCF-7 TAX-2 ), or docetaxel (MCF-7 TXT ). During selection cells were assessed for drug sensitivity, drug uptake, and the expression of various drug transporters. In all cases, resistance was only achieved when selection reached a specific threshold dose, which was well within the clinical range. A reduction in drug uptake was temporally correlated with the acquisition of drug resistance for all cell lines, but further increases in drug resistance at doses above threshold were unrelated to changes in cellular drug uptake. Elevated expression of one or more drug transporters was seen at or above the threshold dose, but the identity, number, and temporal pattern of drug transporter induction varied with the drug used as selection agent. The pan drug transporter inhibitor cyclosporin A was able to partially or completely restore drug accumulation in the drug-resistant cell lines, but had only partial to no effect on drug sensitivity. The inability of cyclosporin A to restore drug sensitivity suggests the presence of additional mechanisms of drug resistance. This study indicates that drug resistance is achieved in breast tumour cells only upon exposure to concentrations of drug at or above a specific selection dose. While changes in drug accumulation and the expression of drug transporters does occur at the threshold dose, the magnitude of

Effect of irradiation on oxytetracycline residues in poultry meat

Energy Technology Data Exchange (ETDEWEB)

Mazurowski, P [Warsaw Agricultural University, Faculty of Veterinary Medicine, Department of Food Hygiene, Warsaw (Poland)

1994-12-31

The purpose of the study was an evaluation of the effect of ionizing radiation on detection of oxytetracycline residues in poultry meat. Oxytetracycline was chosen as a representative of tetracyclines which are often applied in poultry for therapeutical reasons. The experiment was conducted using both broiler meat treated by oxytetracycline and slurry of broiler meat containing appropriate concentration of this antibiotic. A traditional microbiological method for determination of antibiotics antimicrobial activity was used. A significant decrease of oxytetracycline concentration in meat slurry as a result of irradiation was noted. A dose of 1 kGy reduced concentration of tetracycline to ca 40% and a dose of 3 kGy reduced it to ca 3%. In ground poultry meat a dose of 1 kGy reduced this antibiotic concentration to 70%, a dose of 3 kGy reduced oxytetracycline concentration to 35% and a 5 kGy dose reduced it up to ca 18% of initial concentration. It can be concluded that irradiation of poultry meat with radurization doses can cause some difficulties in detection of tetracycline residues in meat using traditional microbiological methods of detection. (author).

Effect of irradiation on oxytetracycline residues in poultry meat

International Nuclear Information System (INIS)

Mazurowski, P.

1994-01-01

The purpose of the study was an evaluation of the effect of ionizing radiation on detection of oxytetracycline residues in poultry meat. Oxytetracycline was chosen as a representative of tetracyclines which are often applied in poultry for therapeutical reasons. The experiment was conducted using both broiler meat treated by oxytetracycline and slurry of broiler meat containing appropriate concentration of this antibiotic. A traditional microbiological method for determination of antibiotics antimicrobial activity was used. A significant decrease of oxytetracycline concentration in meat slurry as a result of irradiation was noted. A dose of 1 kGy reduced concentration of tetracycline to ca 40% and a dose of 3 kGy reduced it to ca 3%. In ground poultry meat a dose of 1 kGy reduced this antibiotic concentration to 70%, a dose of 3 kGy reduced oxytetracycline concentration to 35% and a 5 kGy dose reduced it up to ca 18% of initial concentration. It can be concluded that irradiation of poultry meat with radurization doses can cause some difficulties in detection of tetracycline residues in meat using traditional microbiological methods of detection. (author)

Multiclass analysis of antibiotic residues in honey by ultraperformance liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Vidal, Jose Luis Martínez; Aguilera-Luiz, María Del Mar; Romero-González, Roberto; Frenich, Antonia Garrido

2009-03-11

A method has been developed and validated for the simultaneous analysis of different veterinary drug residues (macrolides, tetracyclines, quinolones, and sulfonamides) in honey. Honey samples were dissolved with Na(2)EDTA, and veterinary residues were extracted from the supernatant by solid-phase extraction (SPE), using OASIS HLB cartridges. The separation and determination was carried out by ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS), using an electrospay ionization source (ESI) in positive mode. Data acquisition under MS/MS was achieved by applying multiple reaction monitoring (MRM) of two ion transitions per compound to provide a high degree of sensitivity and specificity. The method was validated, and mean recoveries were evaluated at three concentration levels (10, 50, and 100 microg/kg), ranging from 70 to 120% except for doxycycline, erythromycin, and tylmicosin with recovery higher than 50% at the three levels assayed. Relative standard deviations (RSDs) of the recoveries were less than 20% within the intraday precision and less than 25% within the interday precision. The limits of quantification (LOQs) were always lower than 4 microg/kg. The developed procedure was applied to 16 honey samples, and erythromycin, sarafloxacin, and tylosin were found in a few samples.

Antimicrobial residues in tissues and eggs of laying hens at Chittagong, Bangladesh

Directory of Open Access Journals (Sweden)

Ariful Islam

2016-12-01

Full Text Available Aim: Antimicrobial residue in animal food products is an important index of food safety. Antimicrobial residues could result from chemotherapeutic or chemoprophylactic use of drugs in food animals. This occurrence of residue in animal food products has received enormous worldwide attention from some local, international, and public health agencies. A crosssectional study was conducted from July to December 2009 to detect the antibiotic residues in tissues and eggs of laying hens at Chittagong of Bangladesh. Materials and Methods: Microbial inhibition test (MIT and thin layer chromatography (TLC methods were used to detect antibacterial residues in poultry tissues (liver, kidney, breast, and thigh muscles and eggs. The bacteria and pH of the MIT method were as follows: Bacillus subtilis on test agar medium with a pH of 7.2, Bacillus cereus with a pH of 6.0, and Escherichia coli at pH with an 8.0. Results: The overall prevalence of antibiotic residues detected by MIT was 64% in liver, 63% in kidney, 56% in breast muscle, 50% in thigh muscle, and 60% in eggs. There was significant variation in results between MIT and TLC (p<0.05. Tetracycline residues were found in 48% in liver, 24% in kidneys, 20% in thigh muscles, 26% in breast muscles, and 36% in eggs. Ciprofloxacin residues were found 46% in liver, 42% in kidneys, 34% in thigh muscles, 30% in breast muscles, and 30% in eggs. Enrofloxacin residues were found 40% in livers, 36% in kidneys, 24% in thigh muscles, 20% in breast muscles, and 26% in eggs. Amoxicillin residues were found 48% in livers, 30% in kidneys, 26% in thigh muscles, 22% in breast muscles, and 24% in eggs. The most frequently detected antibiotic residues by both MIT and TLC were found in liver tissue, tetracycline (48%, ciprofloxacin (46%, enrofloxacin (40%, and amoxicillin (42% were found in liver. Breast muscle tissue was least likely to contain antibiotic residues (24%. Tetracycline (p=0.01 and amoxicillin (p=0.03 residues had

On the role of the residual stress state in product manufacturing

NARCIS (Netherlands)

Zijlstra, G.; Groen, M.; Post, J.; Ocelik, V.; de Hosson, J.Th.M.

2016-01-01

This paper concentrates on the effect of the residual stress state during product manufacturing of AISI 420 steel on the final shape of the product. The work includes Finite Element (FE) calculations of the distribution of the residual stresses after metal forming and a heat treatment. The evolution

Pesticide residues in birds and mammals

Science.gov (United States)

Stickel, L.F.; Edwards, C.A.

1973-01-01

exposure to an organochlorine pesticide, the concentrations of residues in the different tissues are ordinarily directly correlated with each other. When the dosage is at lethal levels, or when stored residues are mobilised to lethal levels, the balanced relationship is disrupted. The concentrations of residues in the brain provide the most rigorous criteria for diagnosis of death due to these chemicals, and levels are generally similar across a wide range of species of birds and mammals. Residues in liver are closely correlated with recent dose, either from direct intake or from mobilisation from storage, and so reflect hazardous exposure. Residues in the whole carcass show the storage reserve, and so indicate the potential for adverse effects from lethal mobilisation or from the continuous slow mobilisation that occurs during the normal processes of metabolism and excretion. A synchronous, rapid, and widespread decline in weight and thickness of shells of eggs laid by many species of wild birds occurred in the late 1940's and has persisted. Birds of prey were primarily affected; exceptions apparently are the result of lesser exposure because of different food habits. Many species of fish-eating birds are also affected. Others, however, appear to be more resistant and to accumulate much higher residues before shell-thinning occurs. Seed-eating birds do not appear to have been generally affected; their exposure is ordinarily lower, but physiological factors also seem to be involved. A relationship between shell-thinning and population decline has been established for many species. In exceptional cases, such as the herring gull, persistent re-nesting and other population reactions have overcome adverse effects at the population level. The discovery of shell-thinning among natural populations, and the hypothesis that this thinning was related to the occurrence of organochlorine pesticides, stimulated experimental studies to determine wheth

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

Science.gov (United States)

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

2015-03-01

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

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

Science.gov (United States)

Dieter, M.P.

1975-01-01

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

Gamma exposure rate reduction and residual radium-226 concentrations resulting from decontamination activities conducted at the former uranium millsite in Shiprock, New Mexico

International Nuclear Information System (INIS)

Hans, J.M. Jr.; Hurst, T.L.

1981-01-01

Gamma radiation surveys and residual radium 226 soil samples were taken as part of the decontamination activities of the former Shiprock uranium mill site in New Mexico. In order to facilitate the decontamination activities, the mill site and its contaminated environs were divided into 6 major areas. Extensive data are presented in 2 appendices of the pre- and post-decontamination gamma ray exposure rates made on mill site, and of radium 226 concentrations in surface soil samples. A training program established on the mill site by the Navajo Engineering and Construction Authority is described

On-site treatment and landfilling of MSWI air pollution control residues

DEFF Research Database (Denmark)

Lundtorp, Kasper; Jensen, Dorthe Lærke; Sørensen, Mette Abildgaard

2003-01-01

the process, collected through the drainage system, contained large concentrations of salts (Cl: 14–30 g/l, Na: 4–9 g/l, K: 5–11 g/l, Ca: 2–12 g/l) but low concentrations of trace metals (e.g. Pb: 14–100 μg/l, Cd: leaching......Air pollution control (APC) residues from municipal solid waste incineration (MSWI) are difficult to landfill due to substantial leaching of trace metals. An on-site pretreatment prior to landfilling of APC-residues was investigated in terms of bench-scale experiments with a semidry APC...... of the leaching, concentrations of trace metals were reduced by up to four orders of magnitude....

Use of ultrasound in petroleum residue upgradation

Energy Technology Data Exchange (ETDEWEB)

Sawarkar, A.N.; Pandit, A.B.; Samant, S.D.; Joshi, J.B. [Mumbai Univ., Mumbai (India). Inst. of Chemical Technology

2009-06-15

The importance of bottom-of-the barrel upgrading has increased in the current petroleum refining scenario because of the progressively heavier nature of crude oil. Heavy residues contain large concentrations of metals such as vanadium and nickel which foul catalysts and reduce the potential effect of residue fluidized catalytic cracking. This study showed that the cavitational energy induced by ultrasound be be successfully used to upgrade hydrocarbon mixtures. Conventional processes for the upgrading of residual feedstocks, such as thermal cracking and catalytic cracking, were carried out in the temperature range of 400-520 degrees C. Experiments were performed on 2 vacuum residues, Arabian mix vacuum residue (AMVR) and Bombay high vacuum residue (BHVR) and 1 Haldia asphalt (HA). These were subjected to acoustic cavitation for different reaction times from 15 to 120 minutes at ambient temperature and pressure. Two acoustic cavitation devices were compared, namely the ultrasonic bath and ultrasonic horn. In particular, this study compared the ability of these 2 devices to upgrade the petroleum residues to lighter, more value-added products. Different surfactants were used to examine the effect of ultrasound on upgrading the residue when emulsified in water. In order to better understand the reaction mechanism, a kinetic model was developed based on the constituents of the residue. The ultrasonic horn was found to be more effective in bringing about the upgrading than ultrasonic bath. The study also showed that the acoustic cavitation of the aqueous emulsified hydrocarbon mixture could reduce the asphaltenes content to a greater extent than the acoustic cavitation of non-emulsified hydrocarbon mixture. 20 refs., 11 tabs., 17 figs.

Quadratic residues and non-residues selected topics

CERN Document Server

Wright, Steve

2016-01-01

This book offers an account of the classical theory of quadratic residues and non-residues with the goal of using that theory as a lens through which to view the development of some of the fundamental methods employed in modern elementary, algebraic, and analytic number theory. The first three chapters present some basic facts and the history of quadratic residues and non-residues and discuss various proofs of the Law of Quadratic Reciprosity in depth, with an emphasis on the six proofs that Gauss published. The remaining seven chapters explore some interesting applications of the Law of Quadratic Reciprocity, prove some results concerning the distribution and arithmetic structure of quadratic residues and non-residues, provide a detailed proof of Dirichlet’s Class-Number Formula, and discuss the question of whether quadratic residues are randomly distributed. The text is a valuable resource for graduate and advanced undergraduate students as well as for mathematicians interested in number theory.

Chemical modelling of pore water composition from PFBC residues

International Nuclear Information System (INIS)

Karlsson, L.G.

1991-01-01

The concentration of trace elements varies depending on the source of the coal and also due to the combustion process used. Mercury is one important element among the trace elements in the coal residues, generally recognised as potentially harmful to the biological system. To predict the pore water concentrations of mercury and other important constituents leached from coal combustion residues disposal sites, mechanistic data on chemical reactions are required. The present study is an application of a basially thermodynamical approach using the geochemical code EQ3NR. The presence of discrete solid phases that control the aqueous concentrations of major elements such as aluminium, calcium and silicon are identified. Solid phases are modelled in equilibrium with a hypothetical pore water at a pH range of 7-11. In this study the thermodynamic database of EQ3NR has been complemented with data for cadmium, mercury and lead taken from the OECD/NEA Thermodynamic Database and from a compilation made by Lindsay. Possible solubility limiting phases for the important trace elements arsenic, cadmium, chromium, copper, mercury, nickel and lead have been identified. Concentrations of these trace elements as a function of pH in the hypothetical pore water were calculated using mechanistic thermodynamial data. The thermodynamical approach in this study seems justified because most solid residues that are either present or expected to form during weathering have relatively fast precipitation/dissolution kinetics. (21 refs., 18 figs., 5 tabs.)

A combined process of adsorption and Fenton-like oxidation for furfural removal using zero-valent iron residue.

Science.gov (United States)

Li, Furong; Bao, Jianguo; Zhang, Tian C; Lei, Yutian

2015-01-01

In this study, the feasibility of using a combined adsorption and Fenton-like oxidation process (with zero-valent iron (ZVI) residue from heat wraps as an absorbent and catalyst) to remove furfural in the solution was evaluated. The influencing parameters (e.g. pH, H2O2 concentration, initial furfural concentration) and the reusability of ZVI residue (to replace the iron powder) were estimated. The ZVI residue was found to have much better adsorption effect on furfural at pH 2.0 compared with pH 6.7. For Fenton-like reaction alone with ZVI residue, the highest furfural removal of 97.5% was observed at the concentration of 0.176 mol/L H2O2, and all of the samples had >80% removal efficiency at different initial furfural concentrations of 2, 10, 20, 30 and 40 mmol/L. However, with a combined adsorption and Fenton-like oxidation, the removal efficiency of furfural was nearly 100% for all treatments. The ZVI residue used for furfural removal was much better than that of iron powder in the Fenton-like reaction at a seven-cycle experiment. This study suggests the combined process of adsorption and Fenton-like oxidation using ZVI residue is effective for the treatment of furfural in the liquid.

Prolonged persistence of residual Wuchereria bancrofti infection after cessation of diethylcarbamazine-fortified salt programme.

Science.gov (United States)

Ramaiah, K D; Thiruvengadam, B; Vanamail, P; Subramanian, S; Gunasekaran, S; Nilamani, N; Das, P K

2009-08-01

A diethylcarbamazine (DEC)-fortified salt intervention programme was implemented between 1982 and 1986 in Karaikal district, Union territory of Pondicherry, south India, to control Culex transmitted bancroftian filariasis. The intervention reduced the microfilaria (Mf) rate from 4.49% to 0.08%. To eliminate the residual microfilaraemia, the health department detected and treated Mf carriers from 1987 to 2005 and mass-administered drugs in 2004 and 2005. Surveillance from 1987 to 2005 revealed persistent microfilaraemia in 0.03-0.42% of the population. In 2006, we conducted a more detailed Mf survey and a child antigenaemia (Ag) survey in 15 urban wards and 17 rural villages. These surveys showed an overall Mf rate of 0.46% in the high-risk urban areas and 0.18% in the rural areas; none of the sampled children was positive for Ag. All detected Mf carriers were >20 years old. The age of the youngest Mf carrier was 30 years in urban and 21 years in rural areas, which suggests that transmission was interrupted and there was no incidence of new Mf case after cessation of DEC salt programme. Eleven of 15 urban and 15 of 17 villages were totally free from microfilaraemia. Nevertheless, three of 15 surveyed urban localities and two of 17 villages showed >1% Mf rate. Thus, it seems that (i) post-intervention very low levels of microfilaraemia can continue as long as 20 years; (ii) 0.60-0.70% Mf rate is a safe level and at this level recrudescence of infection may not occur; (iii) there can be isolated localities with >1% Mf rate and their detection for further intervention measures could be challenging in larger control/elimination programmes and (iv) the residual infection mostly gets concentrated in the adult population, in underdeveloped urban areas and in historically highly endemic or large endemic rural areas. These groups and areas should be targeted with rigorous intervention measures such as mass drug administration to eliminate the residual infection.

Treatment and processing of residues of fermentation; Behandlung und Verwertung von Gaerrueckstaenden

Energy Technology Data Exchange (ETDEWEB)

Doehler, H.; Schliebner, P. [Kuratorium fuer Technik und Bauwesen in der Landwirtschaft (KTBL), Darmstadt (Germany)

2007-07-01

With the transformation of the EEG (Renewable Energy Resources Act), the number of biogas plants increased rapidly. Additionally, an enlargement of the performance of the plants and a regional concentration process take place. Recently, processing routes for liquid manure will be considered in order to reduce problems of the surplus of nutrients as well as the costs of the transport of the water-rich residues of fermentation. Under this aspect, the authors of the contribution under consideration report on procedures for the processing of residues of fermentation as well as costs and utilization of these procedures. By the example of an agrarian society, four procedures for the output and processing of residues of fermentation are compared with one another regarding to expenditure of work time, investments and economy: Output of residues of fermentation, treatment of residues of fermentation by separation, processing of residues of fermentation by means of diaphragm technology, processing of residues of fermentation by means of evaporation technology. The processing routes reduce the residues of fermentation by 60 %. Thus, the costs of output and the necessary storage capacities for residues of fermentation are reduced. Presently, no savings regarding to work completion by the processing of the residues of fermentation can be obtained. The specific total costs of the investigated procedures are between 2.64 Euro/m{sup 3} according to the procedure with separation and to 8.64 Euro/m{sup 3} according to the diaphragm processing route. An enhanced demand of investment does not cause compellingly the highest specific total costs of the procedures. In comparison to the output of residues of fermentation, the examined procedures for the processing of residues of fermentation do not result in economical and ergonomic advantages. The high costs of investment and operating cost of the processing of residues of fermentation cannot be compensated by the reduced costs of output

Chemical modifications of therapeutic proteins induced by residual ethylene oxide.

Science.gov (United States)

Chen, Louise; Sloey, Christopher; Zhang, Zhongqi; Bondarenko, Pavel V; Kim, Hyojin; Ren, Da; Kanapuram, Sekhar

2015-02-01

Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. However, specific identification of EtO adducts in proteins and the effect of residual EtO on the stability of therapeutic proteins has not been reported to date. This paper describes studies of residual EtO with two therapeutic proteins, a PEGylated form of the recombinant human granulocyte colony-stimulating factor (Peg-GCSF) and recombinant human erythropoietin (EPO) formulated with human serum albumin (HSA). Peg-GCSF was filled in an EtO sterilized delivery device and incubated at accelerated stress conditions. Glu-C peptide mapping and LC-MS analyses revealed residual EtO reacted with Peg-GCSF and resulted in EtO modifications at two methionine residues (Met-127 and Met-138). In addition, tryptic peptide mapping and LC-MS analyses revealed residual EtO in plastic vials reacted with HSA in EPO formulation at Met-328 and Cys-34. This paper details the work conducted to understand the effects of residual EtO on the chemical stability of protein therapeutics. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

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

Science.gov (United States)

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

2017-01-01

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

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

Directory of Open Access Journals (Sweden)

Szandra Klátyik

2017-09-01

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

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

Science.gov (United States)

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

2016-03-01

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

Investigations for the radiotechnology of drugs

International Nuclear Information System (INIS)

Poehland-Block, H.

1972-01-01

The radiation technology of drugs is investigated. The following groups or substances are individually dealt with: 1) Investigations on enzymes: determination of the residual germ number and the residual activity of pancreatin and bromelin after irradiation with 60 Co gamma radiation. 2) Investigations on 60 Co gamma-irradiated emulsifiers from the polyethylene glycolsorbitan fatty acid ester series, on thus produced and on irradiated emulsions. 3) Irradiation and testing of granulatum simplex and tablets prepared from this. (EK/LH) [de

Control of drug releasing from biodegradable polymer drug delivery system by gamma-ray irradiation

International Nuclear Information System (INIS)

Yoshioka, Sumie; Aso, Yukio; Kojima, Shigeo

1999-01-01

In order to introduce the drug to the target organ, we developed a gel to control the drug releasing velocity by response to change of temperature by means of γ-ray irradiation to gelatin-GMA modified dextran mixture aqueous solution. A certain level of molecular weight of drug is necessary. The response to the temperature (change of drug releasing velocity) was affected by the concentration of gelatin and the modification rate of GMA. The Higuchi equation was applied to the releasing of β-galactosidase from gelatin-dextran gel and the releasing velocity was calculated. The releasing velocity decreased with increasing GMA modification rate at 37degC and 15degC. The releasing velocity of β-galactosidase decreased with increasing the concentration of gelatin at 15degC, but the velocity increased with increasing the concentration at 37degC. These results indicated that the good drug releasing conditions are obtained by controlling the GMA modification rate and the concentration of gelatin. (S.Y.)

Criteria for the restoration of mining residues in Germany

International Nuclear Information System (INIS)

Kraus, W.; Ettenhuber, E.; Gehrcke, K.; Przyborowski, S.

2000-01-01

Residues from uranium mines and mills and from the mining of silver, tin, cobalt, nickel and other ores, as well as of coal mineralized with uranium, are situated in densely populated regions of Germany. Social and political pressure required an urgent investigation and evaluation of these residues in order to identify relevant residues which could not be disregarded from the radiation protection point of view. There were two categories of residues. First, for huge former uranium mining and milling sites, the original owner could be made liable for restoration. A large Federal rehabilitation programme for the Wismut sites was started immediately after the political change in the former East Germany in 1990 and was based on radiological as well as on social and economic concerns. Secondly, for a large number of smaller residues, sometimes dating back to the middle ages, an evaluation of their radiological relevance was necessary before decisions could be taken on the justification of a restoration. This was the objective of a Federal programme on registration, investigation and evaluation of mining residues. Up to now only minor remedial activities have been carried out in cases where an urgent need had been detected. Criteria developed by the German Commission on radiological protection (SSK) were applied for the evaluation of the residues. The primary criterion for the justification of a restoration was an annual individual effective dose of 1 mSv for all exposure pathways except for the inhalation of radon. For inhalation of radon, the primary criterion for justification was a long term average outdoor radon concentration of 50 Bq/m 3 caused by the residues. Both levels were taken in addition to the natural background radiation level at a given site. These criteria were based on the upper end of the 'normal' range of naturally occurring exposure or concentration levels. SSK established reference levels in measurable quantities (activity concentration in soil

Spectrophotometric Method for Determination of Five 1,4-Dihydropyridine Drugs Using N-Bromosuccinimide and Indigo Carmine Dye

Directory of Open Access Journals (Sweden)

Mohamed A. El Hamd

2013-01-01

Full Text Available Indirect spectrophotometric method is described for quantification of five of 1,4-dihydropyridine (1,4-DHP drugs using N-bromosuccinimide (NBS with the aid of indigo carmine (INC dye. The method is based on addition of known excess of NBS to an acidified solution of 1,4-DHP drugs and determining the residual of NBS through its ability to bleach the colour of the used dye; the amount of NBS that reacted corresponded to the amount of drugs. Beer’s law is obeyed in the concentration range 1.25–13.00 μg/mL. Good correlation coefficients (0.998-0.999 were found between the absorbance values and the corresponding concentrations. Limits of detections ranged from 0.141 to 0.500 μg/mL. The proposed method was successfully applied to the analysis of dosage forms; percent of recoveries ranged from 97.31 to 99.46% without interference from any common excipients. The statistical comparison by Student’s t-test and variance ratio F-test showed no significant difference between the proposed and official or reported methods.

Measurement of residual solvents in a drug substance by a purge-and-trap method.

Science.gov (United States)

Lakatos, Miklós

2008-08-05

The purge-and-trap (P&T) gas extraction method combined with gas chromatography was studied for its suitability for quantitative residual solvents determination in a water-soluble active pharmaceutical ingredient (API). Some analytical method performance characteristics were investigated, namely, the repeatability, the accuracy and the detection limit of determination. The results show that the P&T technique is--as expected--more sensitive than the static headspace, thus it can be used for the determination of residual solvents pertaining to the ICH Class 1 group. It was found that it could be an alternative sample preparation method besides the static headspace (HS) method.

Radioactivity of combustion residues from coal-fired power stations

International Nuclear Information System (INIS)

Vom Berg, W.; Puch, K.H.

1996-01-01

Each year in Germany, about 18 mill. t of combustion residues are produced from the combustion of bituminous coal and lignite. They are utilized to a great extent in the construction industry and in mining. During the combustion of coal, the radio-nuclides remain predominantly in the ash. The radionuclide concentration in lignite ash is within the range of that in natural soil. The combustion residues of bituminous coal contain radio-nuclides of a similar order of magnitude as also can occur in natural rock. The utilization of combustion residues in construction materials makes a negligible contribution to radiation exposure through retention in buildings. (orig.) [de

Gewichtsverlies, serumnatriumconcentratie en restverschijnselen bij patiëntjes met hypertone dehydratie door onvoldoende borstvoeding [Weight loss, serum sodium concentration and residual symptoms in patients with hypernatremic dehydration caused by insufficient breastfeeding

NARCIS (Netherlands)

Breuning-Boers, J.M.; Dommelen, P. van; Wouwe, J.P. van; Verkerk, P.H.

2006-01-01

Objective. To determine the relationship between serum sodium concentration and weight loss as well as residual symptoms in newborns with hypernatremic dehydration caused by insufficient breastfeeding; and to determine the sensitivity of the following rule of thumb 'if weight loss is less than 10%,

The potential of residues of furfural and biogas as calcareous soil amendments for corn seed production.

Science.gov (United States)

Zhao, Yunchen; Yan, Zhibin; Qin, Jiahai; Ma, Zhijun; Zhang, Youfu; Zhang, Li

2016-04-01

Intensive corn seed production in Northwest of China produced large amounts of furfural residues, which represents higher treatment cost and environmental issue. The broad calcareous soils in the Northwest of China exhibit low organic matter content and high pH, which led to lower fertility and lower productivity. Recycling furfural residues as soil organic and nutrient amendment might be a promising agricultural practice to calcareous soils. A 3-year field study was conducted to evaluate the effects of furfural as a soil amendment on corn seed production on calcareous soil with compared to biogas residues. Soil physical-chemical properties, soil enzyme activities, and soil heavy metal concentrations were assessed in the last year after the last application. Corn yield was determined in each year. Furfural residue amendments significantly decreased soil pH and soil bulk density. Furfural residues combined with commercial fertilizers resulted in the greater cumulative on soil organic matter, total phosphorus, available phosphorus, available potassium, and cation exchange capacity than that of biogas residue. Simultaneously, urease, invertase, catalase, and alkaline phosphatase increased even at the higher furfural application rates. Maize seed yield increased even with lower furfural residue application rates. Furfural residues resulted in lower Zn concentration and higher Cd concentration than that of biogas residues. Amendment of furfural residues led to higher soil electrical conductivity (EC) than that of biogas residues. The addition of furfural residues to maize seed production may be considered to be a good strategy for recycling the waste, converting it into a potential resource as organic amendment in arid and semi-arid calcareous soils, and may help to reduce the use of mineral chemical fertilizers in these soils. However, the impact of its application on soil health needs to be established in long-term basis.

Lindane residues in fish inhabiting Nigerian rivers

International Nuclear Information System (INIS)

Okereke, G.U.; Dje, Y.

1997-01-01

Analysis for residues of lindane in fish collected from various rivers close to rice agroecosystems showed that the concentrations of lindane ranged from none detectable to 3.4 mg kg -1 . Fish from rivers where strict regulations prohibits its use had no detectable lindane residues while appreciable amounts of lindane were found in fish were such restriction was not enforced with the variation attributed to the extent of use of lindane in the area of contamination. The investigation confirms that the use of lindane in rice production in Nigeria can cause the contamination of fish in nearby rivers. (author). 16 refs, 2 tab

Human drug metabolism: an introduction

National Research Council Canada - National Science Library

Coleman, Michael D

2010-01-01

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

Validation of the BetaStar® Advanced for Beta-lactams Test Kit for the Screening of Bulk Tank and Tanker Truck Milks for the Presence of Beta-lactam Drug Residues.

Science.gov (United States)

Denhartigh, Andrew; Reynolds, Lindsay; Palmer, Katherine; Klein, Frank; Rice, Jennifer; Rejman, John J

2018-05-18

A validation study was conducted for an immunochromatographic method (BetaStar ® Advanced for Beta-lactams) for the detection of beta-lactam residues in raw, commingled bovine milk. The assay detected amoxicillin, ampicillin, cloxacillin, penicillin, cephapirin, and ceftiofur below the U.S. Food and Drug Administration tolerance levels but above the maximum sensitivity thresholds established by the National Conference on Interstate Milk Shipments. The results of internal and independent laboratory dose-response studies employing spiked samples were in agreement. The test detected all six drugs at the approximate 90/95% sensitivity levels in milk from cows treated with each drug. Selectivity of the assay was 100%, as no false-positive results were obtained in testing 1148 control milk samples. Testing the estimated 90/95% sensitivity level for amoxicillin (8.5 ppb), ampicillin (6.9 ppb), cloxacillin (8.9 ppb), penicillin (4.2 ppb), and cephapirin (17.6 ppb), and at 100 ppb for each antibiotic, resulted in 94-100% positive tests for each of the beta-lactam drugs. The results of ruggedness experiments established the operating parameter tolerances for the assay. Cross-reactivity testing established that the assay detects other certain beta-lactam drugs, but it does not cross-react with any of 30 drugs belonging to seven different drug classes. Abnormally high bacterial or somatic cell counts in raw milk produced no assay interference.

Safe apples for baby-food production: survey of pesticide treatment regimes leaving minimum residues.

Science.gov (United States)

Ticha, Jana; Hajslova, Jana; Kovalczuk, Tomas; Jech, Martin; Honzicek, Jiri; Kocourek, Vladimir; Lansky, Miroslav; Kloutvorova, Jana; Falta, Vladan

2007-06-01

A total of 19 pesticide preparations were used according to agricultural practice in six trials in apple orchards. Using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), premature Golden Delicious apples collected 64, 50, 36 days before harvest and mature fruit were examined for residues of active ingredients. No residues of triflumuron, triazamate, chlorpyrifos, etofenprox, fenoxycarb, kresoxim-methyl, cyprodinyl, difenoconazole or thiram were detected in the first sampling. Also, the levels of chlorpyrifos-methyl, penconazole, tebuconazole and tolylfluanid dropped during the pre-harvest interval. Detectable residues of pyridaben, thiacloprid, trifloxystrobin and tetraconazole in harvested fruits were below 0.01 mg kg(-1), which is the maximum concentration of residues acceptable by baby-food producers in any raw material. The only residues exceeding this concentration were captan and teflubenzuron. Based on the data, farmers can choose pesticides for optimal treatment of plants, while enabling growth of a safe crop suitable for baby-food production.

USAGE OF ALGAE SPECIES CHAETOMORPHA GRACILIS AND CH. AEREA FOR DEPURATION PROCESS OF THE RESIDUAL WATERS

Directory of Open Access Journals (Sweden)

SALARU VICTOR

2008-11-01

Full Text Available Rapid increase of the population on the globe scale imposes maximum exploration of the natural resources and first of all of the aquatic resources. As a result are obtained an enormous quantity of residual waters which pollute the waters from rivers, lakes, freatic and underground waters. Elaboration of the depuration methods for residual waters the quantity of which grows continuously, is one of the most up to dated issue of the world. The physical-chemical depuration methods of the residual waters are very expensive and lack the efficiency we would like to have. The most efficient method proved to be the biological method using some species of algae and superior aquatic plants. In our experiences we have involved filamentous green algae Chaetomorpha gracilis and Ch. aerea for depuration of the sewerage water from town Cimishlia. The concentration of the mineral nitrogen compounds in the residual water is around 92,5 mg/l, and of the phosphates 10,1 mg/l. There were used the following concentration of the sewerage water: 10%, 25% and 50%. The most intense development of algae Chaetomorpha aerea was observed in the variant with 10% of residual water, in which the total concentration of the nitrogen was 10,24 mg/l, and of the phosphates 1,05 mg/l. For this variant the depuration water level was about 56,9%. For the case with Chaetomorpha gracilis, the depuration level for the same concentration of the residual water constituted 55,9 %. Increase of the concentration of the polluted water inhibits development of the algae reducing to the minimum their capacity to assimilate the nitrogen and the phosphor. In the solutions with 50 % of residual waters, the algae didn't die, but at the same time they didn't develop. From this results that both algae may be used in the phytoamelioration of the residual waters being diluted at 10% with purified water.

Effects of organic additives on preferred plane and residual stress of copper electroplated on polyimide

International Nuclear Information System (INIS)

Kim, Jongsoo; Kim, Heesan

2010-01-01

Effects of the preferred plane and the residual stress of an electroplated copper on polyethylene glycol (PEG) and 3-N,N-dimethylaminodithiocarbamoyl-1-propanesulfonic acid (DPS) were studied. Polyimide film coated with sputtered copper was used as a substrate. Preferred plane, residual stress, and impurity level in the electroplated copper were measured by an X-ray diffractometry (XRD), calculated by Stoney's equation, and analyzed with secondary ion mass spectroscopy (SMS), respectively. With increasing the concentration of PEG, the preferred plane changed in the order (1 0 0) and (1 1 0) while with increasing the concentration of DPS, the preferred plane changed in the order (1 1 0), (1 0 0), and (1 1 1). Based on the modified preferred growth model, where the amount of additive adsorbed on a plane is newly assumed to be proportional to its surface energy in vacuum, the predicted preferred planes correspond to the experimental results. The residual stress of the electroplated copper depended on the type of additive as well as its concentration but was independent of the preferred plane. For example, PEG and DPS induced tensile and compressive residual stresses in the electroplated copper, respectively, and their magnitudes increased with their concentrations. The dependency of residual stress on the additives was explained by the incorporated additives into the electroplated copper.

Visceral organ weights, digestion and carcass characteristics of beef bulls differing in residual feed intake offered a high concentrate diet.

Science.gov (United States)

Fitzsimons, C; Kenny, D A; McGee, M

2014-06-01

This study examined the relationship of residual feed intake (RFI) with digestion, body composition, carcass traits and visceral organ weights in beef bulls offered a high concentrate diet. Individual dry matter (DM) intake (DMI) and growth were measured in a total of 67 Simmental bulls (mean initial BW 431 kg (s.d.=63.7)) over 3 years. Bulls were offered concentrates (860 g/kg rolled barley, 60 g/kg soya bean meal, 60 g/kg molasses and 20 g/kg minerals per vitamins) ad libitum plus 0.8 kg grass silage DM daily for 105 days pre-slaughter. Ultrasonic muscle and fat depth, body condition score (BCS), muscularity score, skeletal measurements, blood metabolites, rumen fermentation and total tract digestibility (indigestible marker) were determined. After slaughter, carcasses and perinephric and retroperitoneal fat were weighed, carcasses were graded for conformation and fat score and weight of non-carcass organs, liver, heart, kidneys, lungs, gall bladder, spleen, reticulo-rumen full and empty and intestines full, were determined. The residuals of the regression of DMI on average daily gain (ADG), mid-test metabolic BW (BW0.75) and the fixed effect of year, using all animals, were used to compute individual RFI coefficients. Animals were ranked on RFI and assigned to high (inefficient), medium or low groupings. Overall mean ADG and daily DMI were 1.6 kg (s.d.=0.36) and 9.4 kg (s.d.=1.16), respectively. High RFI bulls consumed 7 and 14% more DM than medium and low RFI bulls, respectively (P0.05) for ADG, BW, BCS, skeletal measurements, muscularity scores, ultrasonic measurements, carcass weight, perinephric and retroperitoneal fat weight, kill-out proportion and carcass conformation and fat score. However, regression analysis indicated that a 1 kg DM/day increase in RFI was associated with a decrease in kill-out proportion of 20 g/kg (Pcarcass conformation of 0.74 units (Pcarcass organs did not differ (P>0.05) between RFI groups except for the empty weight of reticulo

A Design of Portable Pesticide Residue Detection System Based on the Enzyme Electrode

Directory of Open Access Journals (Sweden)

Xia SUN

2013-03-01

Full Text Available In this paper, a portable detection system was designed based on amperometric acetylcholinesterase biosensor for rapidly detecting pesticide residues in fruits and vegetables. There were potentiostat, three electrode system, differential amplification circuit and double integral analog to digital (A/D circuit modules in this system. The measurement principle of this system was depended on the weak current from enzyme catalyzing substrate in acetylcholinesterase biosensor for detecting pesticide residues. The weak current generated by the enzyme biosensor was changed into 0-5 V standard voltage signal by this system as an output signal. The proposed system was investigated with eight kinds of standard pesticide of different concentrations, the results showed that the detection limits were all lower than 10 ng/kg. Thus, a new effective home-made system of detecting pesticide residues with portable, easy-to-use, fast response was developed. The pesticide residues rapid detection system can collect the weak current signal generated by electrochemical reaction and on-site detect the concentration of pesticide residues in real fruits and vegetables samples.

The effect of commercial processing procedures on 14C-carbendazim residues in soybean oil and tomato

International Nuclear Information System (INIS)

Peng Genyuan; Wang Huaguo; Qi Mengwen; Wang Fujun; Zhou Changjiu

1994-01-01

Under simulated agricultural practices, soybean plants were treated with 14 C-labelled carbendazim during the blooming stage. The residue in seeds was determined to be 0.067 ppm; corresponding to 0.076 ppm respectively. After subjecting the oil to degumming, alkali treatment, bleaching and deodorization, 53.7% of original radioactivity was removed. Deodorization was the most effect process, removing about 20% of the residue. The concentration of residues in the deodorized oil decreased about 30%. In soybean seed and cake, the residue was mainly present as carbendazim, the concentration of the other metabolites did not exceed 30% of the residue. Tomatoes grown on a field plot were treated with 14 C-carbendazim. After harvest, the tomatoes were processed into tomato juice and canned whole fruit. The magnitude and nature of residues in samples taken at several processing steps were determined to evaluate the effect of commercial processing on removing or eliminating the residues. The results showed that the surface residues on tomato would be removed efficiently by simple washing of tomato. A buffer solution of phosphate had the highest efficiency. Tomato juice contained lower residues than canned whole fruit

Analysis of residual toluene in food packaging via headspace extraction method using gas chromatography

International Nuclear Information System (INIS)

Lim, Ying Chin; Mohd Marsin Sanagi

2008-01-01

Polymeric materials are used in many food contact applications as packaging material. The presence of residual toluene in this food packaging material can migrate into food and thus affect the quality of food. In this study, a manual headspace analysis was successfully designed and developed. The determination of residual toluene was carried out with standard addition method and multiple headspace extraction, MHE) method using gas chromatography-flame ionization detector, GC-FID). Identification of toluene was performed by comparison of its retention time with standard toluene and GC-MS. It was found that the suitable heating temperature was 180 degree Celsius with an optimum heating time of 10 minutes. The study also found that the concentration of residual toluene in multicolored sample was higher compared to mono colored sample whereas residual toluene in sample analyzed using standard addition method was higher compared to MHE method. However, comparison with the results obtained from De Paris laboratory, France found that MHE method gave higher accuracy for sample with low analyte concentration. On the other hand, lower accuracy was obtained for sample with high concentration of residual toluene due to systematic errors. Comparison between determination methods showed that MHE method is more precise compared to standard addition method. (author)

Multi-class multi-residue analysis of veterinary drugs in meat using enhanced matrix removal lipid cleanup and liquid chromatography-tandem mass spectrometry.

Science.gov (United States)

Zhao, Limian; Lucas, Derick; Long, David; Richter, Bruce; Stevens, Joan

2018-05-11

This study presents the development and validation of a quantitation method for the analysis of multi-class, multi-residue veterinary drugs using lipid removal cleanup cartridges, enhanced matrix removal lipid (EMR-Lipid), for different meat matrices by liquid chromatography tandem mass spectrometry detection. Meat samples were extracted using a two-step solid-liquid extraction followed by pass-through sample cleanup. The method was optimized based on the buffer and solvent composition, solvent additive additions, and EMR-Lipid cartridge cleanup. The developed method was then validated in five meat matrices, porcine muscle, bovine muscle, bovine liver, bovine kidney and chicken liver to evaluate the method performance characteristics, such as absolute recoveries and precision at three spiking levels, calibration curve linearity, limit of quantitation (LOQ) and matrix effect. The results showed that >90% of veterinary drug analytes achieved satisfactory recovery results of 60-120%. Over 97% analytes achieved excellent reproducibility results (relative standard deviation (RSD) meat matrices. The matrix co-extractive removal efficiency by weight provided by EMR-lipid cartridge cleanup was 42-58% in samples. The post column infusion study showed that the matrix ion suppression was reduced for samples with the EMR-Lipid cartridge cleanup. The reduced matrix ion suppression effect was also confirmed with 30%) for all tested veterinary drugs in all of meat matrices. The results showed that the two-step solid-liquid extraction provides efficient extraction for the entire spectrum of veterinary drugs, including the difficult classes such as tetracyclines, beta-lactams etc. EMR-Lipid cartridges after extraction provided efficient sample cleanup with easy streamlined protocol and minimal impacts on analytes recovery, improving method reliability and consistency. Copyright © 2018 Elsevier B.V. All rights reserved.

Repurposing salicylanilide anthelmintic drugs to combat drug resistant Staphylococcus aureus.

Science.gov (United States)

Rajamuthiah, Rajmohan; Fuchs, Beth Burgwyn; Conery, Annie L; Kim, Wooseong; Jayamani, Elamparithi; Kwon, Bumsup; Ausubel, Frederick M; Mylonakis, Eleftherios

2015-01-01

Staphylococcus aureus is a Gram-positive bacterium that has become the leading cause of hospital acquired infections in the US. Repurposing Food and Drug Administration (FDA) approved drugs for antimicrobial therapy involves lower risks and costs compared to de novo development of novel antimicrobial agents. In this study, we examined the antimicrobial properties of two commercially available anthelmintic drugs. The FDA approved drug niclosamide and the veterinary drug oxyclozanide displayed strong in vivo and in vitro activity against methicillin resistant S. aureus (minimum inhibitory concentration (MIC): 0.125 and 0.5 μg/ml respectively; minimum effective concentration: ≤ 0.78 μg/ml for both drugs). The two drugs were also effective against another Gram-positive bacteria Enterococcus faecium (MIC 0.25 and 2 μg/ml respectively), but not against the Gram-negative species Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter aerogenes. The in vitro antimicrobial activity of niclosamide and oxyclozanide were determined against methicillin, vancomycin, linezolid or daptomycin resistant S. aureus clinical isolates, with MICs at 0.0625-0.5 and 0.125-2 μg/ml for niclosamide and oxyclozanide respectively. A time-kill study demonstrated that niclosamide is bacteriostatic, whereas oxyclozanide is bactericidal. Interestingly, oxyclozanide permeabilized the bacterial membrane but neither of the anthelmintic drugs exhibited demonstrable toxicity to sheep erythrocytes. Oxyclozanide was non-toxic to HepG2 human liver carcinoma cells within the range of its in vitro MICs but niclosamide displayed toxicity even at low concentrations. These data show that the salicylanilide anthelmintic drugs niclosamide and oxyclozanide are suitable candidates for mechanism of action studies and further clinical evaluation for treatment of staphylococcal infections.

Impact of Vial Capping on Residual Seal Force and Container Closure Integrity.

Science.gov (United States)

Mathaes, Roman; Mahler, Hanns-Christian; Roggo, Yves; Ovadia, Robert; Lam, Philippe; Stauch, Oliver; Vogt, Martin; Roehl, Holger; Huwyler, Joerg; Mohl, Silke; Streubel, Alexander

2016-01-01

The vial capping process is a critical unit operation during drug product manufacturing, as it could possibly generate cosmetic defects or even affect container closure integrity. Yet there is significant variability in capping equipment and processes, and their relation to potential defects or container closure integrity has not been thoroughly studied. In this study we applied several methods-residual seal force tester, a self-developed system of a piezo force sensor measurement, and computed tomography-to characterize different container closure system combinations that had been sealed using different capping process parameter settings. Additionally, container closure integrity of these samples was measured using helium leakage (physical container closure integrity) and compared to characterization data. The different capping equipment settings lead to residual seal force values from 7 to 115 N. High residual seal force values were achieved with high capping pre-compression force and a short distance between the capping plate and plunge. The choice of container closure system influenced the obtained residual seal force values. The residual seal force tester and piezoelectric measurements showed similar trends. All vials passed physical container closure integrity testing, and no stopper rupture was seen with any of the settings applied, suggesting that container closure integrity was warranted for the studied container closure system with the chosen capping setting ranges. The vial capping process is a critical unit operation during drug product manufacturing, as it could possibly generate cosmetic defects or even affect container closure integrity. Yet there is significant variability in capping equipment and processes, and their relation to potential defects or container closure integrity has not been thoroughly studied. In this study we applied several methods-residual seal force tester, a self-developed system of a piezo force sensor measurement, and

Chemical modelling of trace elements in pore water from PFBC residues containing ammonia

International Nuclear Information System (INIS)

Karlsson, L.G.; Brandberg, F.

1993-01-01

Ammonia is added to the PFBC process with the purpose to reduce the emissions of NO x in the stack gases. The design of the system for cleaning the stack gases will lead to an increased adsorption of ammonia and an accumulation of soluble ammonium salts in the cyclone ash from PFBC processes. This can be an environmental problem since the amounts will increase over the coming years and there will be a need to dispose the residues. When infiltrating rainwater penetrates the disposed residues ammonia and ammonium salts result in a contamination of the pore water with ammonia in the disposed residues. This entail the solubility of several trace elements in the residues that form soluble complexes with ammonia will increase and cause an increased contamination of groundwater and surface water. In this study the increased solubilities is calculated for the trace elements cadmium, cobalt, copper, mercury, nickel, silver and zinc in the residues using thermodynamical data. The calculations have been performed with probable solid phases of the trace elements at oxidizing and reducing conditions as a function of pH and at varying concentration of ammonia in the pore water. The thermodynamic calculations have been performed with the geochemical code EQ3NR. The results from the calculations show that as a concentration of 17 mg NH 3 /l in the pore water of the residues increases the solubilities for copper and silver. If the concentration of ammonia increases to 170 mg NH 3 /l will the solubilities increase also for cadmium, nickel and zinc. (12 refs., 39 figs.)

Quantification of heavy metals from residual waste and ashes from the treatment plant of residual water Reciclagua and,effects for the health of those workers which manipulate those residuals

International Nuclear Information System (INIS)

Guerrero D, J.J.

2004-01-01

concentrations greater than 0.5% in weight, as long as the analysis of plasma emission spectroscopy very low concentrations are identified already that this method causes the destruction of the sample achieving the identification of all the present elements. With the obtained results we are able to compare the concentrations of the metals before and after the leaching and we calculate by this way the percentage of efficiency for each one of the variables that were managed in the development of the study, obtaining the extraction of those toxic, and valuable metals, present in the muds until of 100%. Based on the results we can mention that the workers are exposed to aerosols and powders of these toxic residuals which contain heavy metals. (Author)

Viscoelastic properties of microfibrillated cellulose (MFC) produced from agricultural residue corn stover

Science.gov (United States)

The rheological properties of microfibrillated cellulose (MFC) produced from agricultural residue corn stover were investigated. The corn stover MFC gels exhibited concentration-dependent viscoelastic properties. Higher corn stover MFC concentrations resulted in stronger viscoelastic properties. Th...

Functional residual capacity measurement by heptafluoropropane in ventilated newborn lungs

OpenAIRE

Kusztrich, Ariane

2012-01-01

Objective: Heptafluoropropane is an inert gas commercially used as propellant for inhalers. Since heptafluoropropane can be detected in low concentrations, it could also be used as a tracer gas to measure functional residual capacity. The aim of the present study was to validate functional residual capacity measurements by heptafluoropropane wash-in/wash-out (0.8%) during mechanical ventilation in small, surfactant-depleted lungs using a newborn piglet model. Design: Prospective laborato...

Optimization of prehydrolysis time and substrate feeding to improve ethanol production by simultaneous saccharification and fermentation of furfural process residue.

Science.gov (United States)

He, Jianlong; Zhang, Wenbo; Liu, Xiaoyan; Xu, Ning; Xiong, Peng

2016-11-01

Ethanol is a very important industrial chemical. In order to improve ethanol productivity using Saccharomyces cerevisiae in fermentation from furfural process residue, we developed a process of simultaneous saccharification and fermentation (SSF) of furfural process residue, optimizing prehydrolysis cellulase loading concentration, prehydrolysis time, and substrate feeding strategy. The ethanol concentration obtained from the optimized process was 19.3 g/L, corresponding 76.5% ethanol yield, achieved by running SSF for 48 h from 10% furfural process residue with prehydrolysis at 50°C for 4 h and cellulase loading of 15 FPU/g furfural process residue. For higher ethanol concentrations, fed-batch fermentation was performed. The optimized fed-batch process increased the ethanol concentration to 37.6 g/L, 74.5% yield, obtained from 10% furfural process residue with two additions of 5% substrate at 12 and 24 h. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Residue levels and risk assessment of pesticides in nuts of China.

Science.gov (United States)

Liu, Yihua; Shen, Danyu; Li, Shiliang; Ni, Zhanglin; Ding, Ming; Ye, Caifen; Tang, Fubin

2016-02-01

The pesticide residue levels of three nuts (chestnut, walnut, pinenut) collected from seven main producing areas of China were investigated. Twenty-nine pesticides, including organophosphates (OPs), organochlorines (OCs), pyrethroids (PYs) and two fungicides (triadimefon and buprofezin) were analyzed by gas chromatography (GC). Four OPs (acephate, dimethoate, chlorpyrifos and parathion-methyl) were found in 11.4% samples, with the concentrations of 19.0 µg kg(-1) to 74.0 µg kg(-1). Six OCs (DDT, HCH, endosulfan, quintozene, aldrin and dieldrin) were found in 18.2% samples, with the concentrations of 2.0 µg kg(-1) to 65.7 µg kg(-1). Among OCs, p,p-DDE and α-HCH were the dominant isomer for DDT and HCH. Five PYs (fenpropathrin, fenvalerate, cypermethrin, bifenthrin and cyhalothrin) were found in 15.9% samples, with the concentrations of 2.5 µg kg(-1) to 433.0 µg kg(-1). Fenpropathrin was the most frequently detected pesticide. In addition, triadimefon and buprofezin were detected only in two samples. For the tested nuts, 25.0% samples with multiple residues (containing more than two pesticides) were noted, even up to 9.1% samples with five pesticide residues. The residue of 15.9% samples was higher than the maximum residue limits (MRLs) of China. The short-term risks for the tested nuts were below 1.2%, and the highest long-term risk was 12.58%. The cumulative risk (cHI) for the tested pesticides were 8.43% (OPs), 0.42% (OCs), 12.82% (PYs) and 0.15% (fungicides), respectively. The total cHI was 21.82%. There was no significant health risk for consumers via nuts consumption. Copyright © 2015 Elsevier Ltd. All rights reserved.

Water quality in coastal wetlands: illicit drugs in surface waters of L'Albufera Natural Park (Valencia, Spain)

Science.gov (United States)

Vazquez-Roig, P.; Blasco, C.; Andreu, V.; Pascual, J. A.; Rubio, J. L.; Picó, Y.

2010-05-01

A wide range of emerging pollutants have been identified in environment: antibiotics, hormones, personal care products, etc. But quite recently a new class of ecological threat has been reported: the presence in waters of abuse drugs coming from human consumption [1,2]. Treatment of wastewaters may remove a portion of these compounds, but sometimes, these treatments are insufficient or nonexistent, residues can reach into the aquatic environment. ĹAlbufera Natural Park (Valencia, Spain) is a marsh area of a great interest because it is the habitat of a large quantity of unique species of flora and fauna, and a zone of refuge, feeding and breeding for a large number of migratory birds. However, this area is threatened by urban, industrial and agricultural pressures. The aim of this work has been to develop a fast and sensitive multi-residue analytical method for to establish the occurrence and distribution of commonly consumed illicit drugs in surface waters of ĹAlbufera lake. A representative set of abuse drugs with different mode of action was chosen for this purpose, including: amphetaminics, opiates, cocainics and cannabinoids (THC and nor-9-carboxy-THC). In April 2008 and October 2008 a total of 16 samples of water were collected, corresponding to different sampling points previously designed, and covering the most important channels that flow in to the lake. Samples of 250 mL of water were concentrated by Solid Phase Extraction through an Oasis HLB cartridge and extracted subsequently with methanol as solvent. Quantification was carried out by LC-MS/MS with an ESI interface. Performance characteristics of the PLE-SPE followed by LC-MS/MS were established by validation procedure. Selectivity, linearity, precision, recoveries and limits of detection (LOD) and quantification (LOQ) were studied. Our search shows that current sewage treatment systems do not completely remove illicit drug residues from urban wastewater. Benzoylecgonine, the main metabolite from

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

Science.gov (United States)

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

2018-02-17

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

Mechanism of activity, biosynthesis and identification of beta-lactam antimicrobial drugs

Directory of Open Access Journals (Sweden)

Marija Sedak

2011-01-01

Full Text Available Antimicrobal drugs are chemotherapeutics with a wide spectrum of use in human and veterinary medicine and livestock practice. Beta-lactams are the most widespread group of antimicrobal drugs and are most often used in human and veterinary medicine in the treatment of bacterial infections due to their powerful antimicrobial activity and very low toxicity. They are divided into the groups of penicillins, cefalosporins and monobactams. Penicillins are obtained from the filtrate of the mould cultures Penicillium notatum and Penicillium chrysogenum, while cefalosporins are obtained from the filtrate of the actinomycete cultures (Cephalosporium acremonium. Research has lead to the discovery of active groups of 6-amino-penicillin acids, whose isolation has made it possible to produce semi-synthetic penicillins that have surpassed the limitations of natural penicillin G. The physico-chemical properties of the beta-lactams can be altered by substituting hydrogen in the carboxyl group of penicillins, i.e. in modifying the side chain of cefalosporin. This increases the resistance to the activity of β-lactamase and expands the spectrum of activity. Beta-lactams, in therapy concentrations, act as a bacteriocide by inhibiting the synthesis of bacterial cell walls. Penicillins are important for antibacterial chemotherapy, often in combination with other antimicrobal drugs. Cefalosporins are usually used as a replacement for penicillin in treating infections caused by gram-negative bacteria and in prophylaxis for surgery. The use of beta-lactams in animals used for food can result in the residues of these drugs in meat and meat products or milk and eggs. The introduction of antimicrobal drugs in the human body via food is particularly dangerous due to their direct toxicity or carcinogenicity, influences on the composition of the intestinal microflora, possible allergic reactions in sensitive people, and the appearance of resistance of individual pathogenic

Forest residues in cattle feed

Directory of Open Access Journals (Sweden)

João Elzeário Castelo Branco Iapichini

2012-12-01

Full Text Available The ruminants are capable of converting low-quality food, when they are complementes with high-energy source. Through the use of regional agricultural residues is possible to conduct more economical production systems, since energetic foods have high cost in animal production. There is very abundant availability of residues in agroforestry activities worldwide, so that if a small fraction of them were used with appropriate technical criteria they could largely meet the needs of existing herds in the world and thus meet the demands of consumption of protein of animal origin. The Southwest Region of São Paulo State has large area occupied by reforestation and wide availability of non-timber forest residues, which may represent more concentrated energetic food for ruminant production. This experiment aimed to evaluate the acceptability of ground pine (20, 30 and 40%, replacing part of the energetic food (corn, present in the composition of the concentrate and was performed at the Experimental Station of Itapetininga - Forest Institute / SMA, in the dry season of 2011. It were used four crossbred steers, mean 18 months old, average body weight of 250 kg, housed in a paddock provided with water ad libitum and covered troughs for supplementation with the experimental diet. The adjustment period of the animals was of 07 days and the measurement of the levels of consumption, physiological changes, acceptability and physiological parameters were observed during the following 25 days. The concentrate supplement was formulated based on corn (76.2%, Soybean Meal (20%, urea (2%, Ammonium sulfate (0.4%, calcite (1.4%, Mineral Core (1% and finely ground Pine Cone, replacing corn. In preparing food, the formulas were prepared to make them isoproteic/energetic, containing the following nutrient levels: 22% Crude Protein (CP and 79% of Total Nutrients (TDN. The animals received the supplement in three steps for each level of cone replaced, being offered in the

Persistence and bioaccumulation of oxyfluorfen residues in onion.

Science.gov (United States)

Sondhia, Shobha

2010-03-01

A field study was conducted to determine persistence and bioaccumulation of oxyflorfen residues in onion crop at two growth stages. Oxyfluorfen (23.5% EC) was sprayed at 250 and 500 g ai/ha on the crop (variety, N53). Mature onion and soil samples were collected at harvest. Green onion were collected at 55 days from each treated and control plot and analyzed for oxyfluorfen residues by a validated high-performance liquid chromatography method with an accepted recovery of 78-92% at the minimum detectable concentration of 0.003 microg g(-1). Analysis showed 0.015 and 0.005 microg g(-1) residues of oxyfluorfen at 250 g a.i. ha(-1) rate in green and mature onion samples, respectively; however, at 500 g a.i.ha(-1) rates, 0.025 and 0.011 microg g(-1) of oxyfluorfen residues were detected in green and mature onion samples, respectively. Soil samples collected at harvest showed 0.003 and 0.003 microg g(-1) of oxyfluorfen residues at the doses 250 and 500 g a.i. ha(-1), respectively. From the study, a pre-harvest interval of 118 days for onion crop after the herbicide application is suggested.

Co-sintering of treated APC-residues with bottom ash

DEFF Research Database (Denmark)

Jensen, Dorthe Lærke; Bergfeldt, Britta; Vehlow, Jürgen

2001-01-01

the influence of co-sintering of Ferrox products with bottom ashes on the quality of the residues and the effects on the combustion process. Only few elements showed higher concentrations in the bottom ashes of these co-combustion tests compared to reference tests. No significant effect on the leaching......Air pollution control residues stabilised by means of the Ferrox process can be sager disposed of due to lower contents of soluble salts and lesssoluble heavy metals stabilised in iron oxides. Co-combustion tests in the Karlsruhe test incinerator TAMARA were carried out in order to investigate...... behaviour of the bottom ashes could be found. During the co-combustion process an increase in SO2 concentrations in the raw gas and slightly lower temperatures in the fuel bed could be observed....

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

International Nuclear Information System (INIS)

2002-01-01

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

On-line measurement of residual monomer during polymerisation of acrylamide using ultrasonics

International Nuclear Information System (INIS)

Ponraju, D.; Sebastian, Letha; Viswanathan, S.; Natarajan, A.; Palanichamy, P.; Jayakumar, T.; Baldev Raj

1996-01-01

An ultrasonic technique for the estimation of residual acrylamide monomer during the polymerization of aqueous acrylamide solution has been investigated. Polyacrylamide gel medium serves as a sensitive medium for detection and dosimetry of fast and thermal neutrons. This technique is based on the fact that the velocity of ultrasonic wave increases with the increase in elasticity due to polymerization. The percentage of residual acrylamide monomer is estimated using ultraviolet spectrophotometric analysis. The ultrasonic velocity is correlated with the residual monomer concentration

Nitrofurans residue in broiler chicken meat which analysed by an HPLC

Directory of Open Access Journals (Sweden)

Raphaella Widiastuti

2012-12-01

Full Text Available Furazolidone (FZD, furaltadone (FTD, nitrofurantoin (NFT and nitrofurazone (NFZ are veterinary drugs that belong to the nitrofurans (NFs group and employed as feed additives for growth promotion and theurapetic treatment of gastrointestinal infections caused by Eschericia coli and Salmonella spp. The occurrence of NFs in animal products will end to cause health problem in human consumed such food. This research conducted to study the analysis of NF residues in chicken meat by a high performance liquid chromatography (HPLC and to study the occurrence of NFs residues in samples collected from traditional markets and supermarkets in Bandung, Bogor and Depok. The results of validation method on several parameters for each NF showed that the average of the relative standard deviation (RSD from the precision study were 2.15 to 2.38%, the R2 values of the linearity study were 0.9964 to 0.9995; recoveries were 75.90 % to 91.50 % and the detection limits were 12.01 to 37.25 ng/g. The residual level of NFs for 42 field samples showed that 2 samples positive for NFZ (9.09 and 10.74 ng/g, 1 positive for NFT (10.46 ng/g, 4 positive for FTD (16.44 up to 27.21 ng/g and none positive for FZD. Present results showed that analysis of NFs in broiler chicken meat can be done using an HPLC and the analysis results from field samples showed that these types of drugs were being used for broiler chicken production both as single and/or combination drugs, therefore it is necessary to raise public awareness to monitor the use of NF in livestock production in Indonesia.

GABAergic anxiolytic drug in water increases migration behaviour in salmon

Science.gov (United States)

Hellström, Gustav; Klaminder, Jonatan; Finn, Fia; Persson, Lo; Alanärä, Anders; Jonsson, Micael; Fick, Jerker; Brodin, Tomas

2016-12-01

Migration is an important life-history event in a wide range of taxa, yet many migrations are influenced by anthropogenic change. Although migration dynamics are extensively studied, the potential effects of environmental contaminants on migratory physiology are poorly understood. In this study we show that an anxiolytic drug in water can promote downward migratory behaviour of Atlantic salmon (Salmo salar) in both laboratory setting and in a natural river tributary. Exposing salmon smolt to a dilute concentration of a GABAA receptor agonist (oxazepam) increased migration intensity compared with untreated smolt. These results implicate that salmon migration may be affected by human-induced changes in water chemical properties, such as acidification and pharmaceutical residues in wastewater effluent, via alterations in the GABAA receptor function.

Hydrogenation upgrading of heavy oil residues

Energy Technology Data Exchange (ETDEWEB)

Krichko, A.A.; Maloletnev, A.S.; Mazneva, O.A.; Galkina, N.I. [Fossil Fuel Inst., Moscow (Russian Federation). Hydrogenation and Gasification Dept.; Suvorov, U.P.; Khadjiev, S.N. [Inst. Oil and Chemical Synthesis, Moscow (Russian Federation). Hydrogenation of Heavy Residues Dept.

1997-12-31

At present time in the world there is no simple and effective technology at low pressure (<15-20 MPa) which could give the opportunity to use oil residues for distillate fractions production. In Russia a process for hydrogenation (up 6 MPa hydrogen pressure) of high boiling point (b.p. >520 C) oil products, including high S, V and Ni contents ones, into distillates, feedstock for catalytic cracking (b.p. 360-520 C) and metal concentrates. The main point of the new process is as follows: the water solution of catalytic additive, for which purpose water soluble metal salts of VI-VIII groups are used, is mixed with heavy oil residues, dispersed and then subjected to additional supercavitation in a special apparatus. (orig.)

The effect of different concentrations of bee propolis on skin wound healing and immune response and survival of Common carp (Cyprinus carpio

Directory of Open Access Journals (Sweden)

nasrin choubkar

2014-02-01

Full Text Available Antibiotics use to increase the immune and wound healing in many animals. But due to the residual effects of a drug, Antibiotics and used to increase the immune response and propolis wound healing is aquadic animals. But due to their residual, researchers are looking to replace them with natural materials. One of these natural materials that has many health benefits is bee propolis. The aim of this study was to evaluate the effect of different concentrations of propolis on wound healing and immune system response in common carp (Cyprinus carpio. Propolis extracts were prepared from Kashan Barij essence with different concentrations of 0 , 2 , 5 and 10% with carrier substances (to dissolve the propolis  in water, and were evaluated on wound healing and immune response and survival  of common carp on a 21 –day cycle of short baths once a day . The results showed that, compared with the control group (0%, the use of bee propolis in concentration of 2% has statistically significant difference on wound healing and immune system response in common carp. The use of higher concentrations of propolis healed wound, but increased the number of blood cells (red blood cells, neutrophils, and eosinophils and increased mortality of fish, so it is better to use lower concentrations of propolis in fish. The use bee propolis as additive in water is effective in low concentrations and stimulates the immune system.

The effect of commercial processing procedures on {sup 14}C-carbendazim residues in soybean oil and tomato

Energy Technology Data Exchange (ETDEWEB)

Genyuan, Peng; Huaguo, Wang; Mengwen, Qi; Fujun, Wang; Changjiu, Zhou [Laboratory for the Application of Nuclear Techniques, Beijing Agricultural University, Beijing (China)

1994-06-01

Under simulated agricultural practices, soybean plants were treated with {sup 14}C-labelled carbendazim during the blooming stage. The residue in seeds was determined to be 0.067 ppm; corresponding to 0.076 ppm respectively. After subjecting the oil to degumming, alkali treatment, bleaching and deodorization, 53.7% of original radioactivity was removed. Deodorization was the most effect process, removing about 20% of the residue. The concentration of residues in the deodorized oil decreased about 30%. In soybean seed and cake, the residue was mainly present as carbendazim, the concentration of the other metabolites did not exceed 30% of the residue. Tomatoes grown on a field plot were treated with {sup 14}C-carbendazim. After harvest, the tomatoes were processed into tomato juice and canned whole fruit. The magnitude and nature of residues in samples taken at several processing steps were determined to evaluate the effect of commercial processing on removing or eliminating the residues. The results showed that the surface residues on tomato would be removed efficiently by simple washing of tomato. A buffer solution of phosphate had the highest efficiency. Tomato juice contained lower residues than canned whole fruit.

Washing effects of limonene on pesticide residues in green peppers.

Science.gov (United States)

Lu, Hai-Yan; Shen, Yan; Sun, Xing; Zhu, Hong; Liu, Xian-Jin

2013-09-01

The presence of pesticide residues in food has caused much concern. The low health risks and environmental impacts of limonene make it a very interesting solvent for use in green chemistry. Washing effects of limonene on pesticide residues of methyl chlorpyrifos, chlorothalonil, chlorpyrifos, fenpropathrin and deltamethrin were investigated in green pepper. Results showed that washing with a low concentration of limonene for 5 min (where LOQ is limit of quantitation) caused 53.67%, limonene for 10 min produced 55.90%, limonene for 5 min was the optimal treatment for elimination of pesticide residues in green pepper, considering effect and treatment time as well as cost. © 2013 Society of Chemical Industry.

Residue management at Rocky Flats

International Nuclear Information System (INIS)

Olencz, J.

1995-01-01

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-processclose 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

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

Science.gov (United States)

2011-08-17

... a larger amount of the drug substance than what is intended to be delivered to the patient. This... patient, but also to others, including family members, caregivers, children, and pets. For example...

Dual Drug Loaded Biodegradable Nanofibrous Microsphere for Improving Anti-Colon Cancer Activity

Science.gov (United States)

Fan, Rangrang; Li, Xiaoling; Deng, Jiaojiao; Gao, Xiang; Zhou, Liangxue; Zheng, Yu; Tong, Aiping; Zhang, Xiaoning; You, Chao; Guo, Gang

2016-06-01

One of the approaches being explored to increase antitumor activity of chemotherapeutics is to inject drug-loaded microspheres locally to specific anatomic sites, providing for a slow, long term release of a chemotherapeutic while minimizing systemic exposure. However, the used clinically drug carriers available at present have limitations, such as their low stability, renal clearance and residual surfactant. Here, we report docetaxel (DOC) and curcumin (CUR) loaded nanofibrous microspheres (DOC + CUR/nanofibrous microspheres), self-assembled from biodegradable PLA-PEO-PPO-PEO-PLA polymers as an injectable drug carrier without adding surfactant during the emulsification process. The obtained nanofibrous microspheres are composed entirely of nanofibers and have an open hole on the shell without the assistance of a template. It was shown that these DOC + CUR/nanofibrous microspheres could release curcumin and docetaxel slowly in vitro. The slow, sustained release of curcumin and docetaxel in vivo may help maintain local concentrations of active drug. The mechanism by which DOC + CUR/nanofibrous microspheres inhibit colorectal peritoneal carcinomatosis might involve increased induction of apoptosis in tumor cells and inhibition of tumor angiogenesis. In vitro and in vivo evaluations demonstrated efficacious synergistic antitumor effects against CT26 of curcumin and docetaxel combined nanofibrous microspheres. In conclusion, the dual drug loaded nanofibrous microspheres were considered potentially useful for treating abdominal metastases of colorectal cancer.

Decolorization of textile industry wastewater in solid state fermentation with Peach-Palm (Bactris gasipaes residue

Directory of Open Access Journals (Sweden)

J. A. Chicatto

2018-02-01

Full Text Available Abstract In this work we have assessed the decolorization of textile effluents throughout their treatment in a solid-state fermentation (SSF system. SSF assays were conducted with peach-palm (Bactris gasipaes residue using the white rot fungus Ganoderma lucidum EF 31. The influence of the dye concentration and of the amounts of peach-palm residue and liquid phase on both the discoloration efficiency and enzyme production was studied. According to our results, independently of experimental conditions employed, laccase was the main ligninolytic enzyme produced by G. lucidum. The highest laccase activity was obtained at very low effluent concentrations, suggesting the existence of an inhibitory effect of higher concentrations on fungal metabolism. The highest percentage of color removal was reached when 10 grams of peach palm residue was moistened with 60 mL of the final effluent. In control tests carried out with the synthetic dye Remazol Brilliant Blue R (RBBR decolorization efficiencies about 20% higher than that achieved with the industrial effluent were achieved. The adsorption of RBBR on peach-palm residue was also investigated. Equilibrium tests showed that the adsorption of this dye followed both Langmuir and Freundlich isotherms. Hence, our experimental results indicate that peach-palm residue is suitable substrate for both laccase production and color removal in industrial effluents.

Decolorization of textile industry wastewater in solid state fermentation with Peach-Palm (Bactris gasipaes) residue.

Science.gov (United States)

Chicatto, J A; Rainert, K T; Gonçalves, M J; Helm, C V; Altmajer-Vaz, D; Tavares, L B B

2018-02-15

In this work we have assessed the decolorization of textile effluents throughout their treatment in a solid-state fermentation (SSF) system. SSF assays were conducted with peach-palm (Bactris gasipaes) residue using the white rot fungus Ganoderma lucidum EF 31. The influence of the dye concentration and of the amounts of peach-palm residue and liquid phase on both the discoloration efficiency and enzyme production was studied. According to our results, independently of experimental conditions employed, laccase was the main ligninolytic enzyme produced by G. lucidum. The highest laccase activity was obtained at very low effluent concentrations, suggesting the existence of an inhibitory effect of higher concentrations on fungal metabolism. The highest percentage of color removal was reached when 10 grams of peach palm residue was moistened with 60 mL of the final effluent. In control tests carried out with the synthetic dye Remazol Brilliant Blue R (RBBR) decolorization efficiencies about 20% higher than that achieved with the industrial effluent were achieved. The adsorption of RBBR on peach-palm residue was also investigated. Equilibrium tests showed that the adsorption of this dye followed both Langmuir and Freundlich isotherms. Hence, our experimental results indicate that peach-palm residue is suitable substrate for both laccase production and color removal in industrial effluents.

Techno-economic evaluation of residue exhaustion in batch rectification ethanol production plant

Directory of Open Access Journals (Sweden)

Jaćimović Branislav M.

2017-01-01

Full Text Available This paper presents the techno-economic optimization of batch plant for production of rectified alcohol based on the concentration of ethanol in residue. The aim of the analysis was to determine the extent to which it is economically profitable to exhaust the residual liquid in boiler. The "profit production" criterion is used for calculations.

Fate of trypanocidal drugs in cattle (chemotherapy of trypanosomiasis). Kenya

International Nuclear Information System (INIS)

1992-01-01

This document is the final report of a project to determine the fate of tryponocidal drugs in cattle. Drugs are still the primary agent in the struggle against trypanosomiasis although there is little data on their pharmacokinetics, residue levels, bioavailability rates, etc. This project aimed to provide such information for the three drugs Diminazene aceturate (Berenil), Isometamidium chloride (Samorin) and Homidium bromide (Ethidium). Figs and tabs

Stability of the anthocyanins extracted from residues of the wine industry

Directory of Open Access Journals (Sweden)

Edmar Clemente

2011-09-01

Full Text Available Anthocyanins are highly important due to their antioxidant capacity. They are the most important among the phenolic compounds and one of the main natural dyes used in the food industry. In this research, residue of processed grapes was used to investigate the presence of anthocyanins, the possibility of their extraction from the residue, and their stability. The extraction solution consisted of 70 mL of ethanol 70% and 30 mL of HCl 0.1% at pH 2.0. The results found for the processed grapes residue was 26.20 mg.100 g-1. In order to evaluate stability, caffeic acid was added at 0.5:1 w/v; 0.8:1 w/v; and 1:1 w/v concentrations. Anthocyanins extract reached the greatest stability at 0.5:1 w/v concentration, with 82.47% color retention and a half-life period of 15 days. Therefore, the use of this organic acid as a stabilizer for anthocyanins is feasible.

Analysis of pirlimycin residues in beef muscle, milk and honey by a biotin-streptavidin-amplified enzyme-linked immunosorbent assay

Science.gov (United States)

Food contamination caused by veterinary drug residues is a world-wide public health concern and requires continuous monitoring. In this paper, we describe a biotin–streptavidin-amplified ELISA (BA-ELISA) for detecting pirlimycin residues in beef, milk, and honey. The IC50 value of the BA-ELISA was...

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

Science.gov (United States)

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

2017-12-01

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

Ammonia volatilization from crop residues and frozen green manure crops

Science.gov (United States)

de Ruijter, F. J.; Huijsmans, J. F. M.; Rutgers, B.

2010-09-01

Agricultural systems can lose substantial amounts of nitrogen (N). To protect the environment, the European Union (EU) has adopted several directives that set goals to limit N losses. National Emission Ceilings (NEC) are prescribed in the NEC directive for nitrogen oxides and ammonia. Crop residues may contribute to ammonia volatilization, but sufficient information on their contribution to the national ammonia volatilization is lacking. Experiments were carried out with the aim to assess the ammonia volatilization of crop residues left on the soil surface or incorporated into the soil under the conditions met in practice in the Netherlands during late autumn and winter. Ammonia emission from residues of broccoli, leek, sugar beet, cut grass, fodder radish (fresh and frozen) and yellow mustard (frozen) was studied during two winter seasons using volatilization chambers. Residues were either placed on top of soil or mixed with soil. Mixing residues with soil gave insignificant ammonia volatilization, whereas volatilization was 5-16 percent of the N content of residues when placed on top of soil. Ammonia volatilization started after at least 4 days. Total ammonia volatilization was related to C/N-ratio and N concentration of the plant material. After 37 days, cumulative ammonia volatilization was negligible from plant material with N concentration below 2 percent, and was 10 percent of the N content of plant material with 4 percent N. These observations can be explained by decomposition of plant material by micro-organisms. After an initial built up of the microbial population, NH 4+ that is not needed for their own growth is released and can easily emit as NH 3 at the soil surface. The results of the experiments were used to estimate the contribution of crop residues to ammonia volatilization in the Netherlands. Crop residues of arable crops and residues of pasture topping may contribute more than 3 million kg NH 3-N to the national ammonia volatilization of the

Manual for implementing residual radioactivity guidelines

International Nuclear Information System (INIS)

Gilbert, T.L.; Eckerman, K.F.; Hansen, W.R.; Healy, J.W.; Kennedy, W.E.; Napier, B.A.; Solday, J.K.

1986-01-01

The US Department of Energy (DOE) has recently issued guidelines for residual radioactivity at Formerly Utilized Sites Remedial Action Program (FUSRAP) and remote Surplus Facilities Management Program (SFMP) sites. A manual for implementing these guidelines has been prepared jointly by four DOE laboratories (ANL, LANL, ORNL, and PNL) and is being issued as a supplement to the guidelines. The manual presents procedures and tables for deriving site-specific guidelines for levels of residual radionuclide concentrations in soil that must not be exceeded if a site is to be released for unrestricted use. Guidance for implementing DOE ALARA policy for remedial actions is also included. The concentration factor method is used in the pathway analysis for deriving soil guidelines. The analysis has been structured in a manner that explicitly identifies all of the factors involved. Tables are provided for dose-conversion factors and pathway factors from which environmental transport factors for each radionuclide and pathway may be calculated. The scenarios used for deriving the environmental transport factors and dose conversion factors, and the manner in which the information provided in the manual is used to derive site-specific soil guidelines will be presented

Occurrence of immunosuppressive drugs and their metabolites in the sewage-impacted Vistula and Utrata Rivers and in tap water from the Warsaw region (Poland).

Science.gov (United States)

Giebułtowicz, Joanna; Nałęcz-Jawecki, Grzegorz

2016-04-01

Immunosuppresive therapy following organ transplant frequently includes treatment with tacrolimus and mycophenolic acid derivatives. These pharmaceuticals may enter the environment through wastewater treatment plant (WWTP) effluents and may have a potentially harmful effect on aquatic biota. Tacrolimus, mycophenolic acid and their metabolites were measured at specific points of a large Polish river (Vistula), a smaller river (Utrata) and in tap water samples from the Warsaw region. Analysis was performed using liquid chromatography tandem mass spectrometry, after solid phase extraction for water samples, or QuEChERS extraction for sediments. Residues of tacrolimus were below quantitation limits in both water and sediment samples. However, in water samples mycophenolic acid concentrations were measured at up to 180 ng L(-1) downstream of WWTP outfalls. No immunosuppressive drugs were detected in tap water. Concentrations of mycophenolic acid exceeded the predicted no effect concentration (PNEC) value in some Polish surface water, and risk calculations predicted at least twice higher concentrations in some other countries of the European Union. To the best of the authors' knowledge, this is the first report of these immunosuppressive drug concentrations in the environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of Plasma, Saliva, and Hair Levetiracetam Concentrations.

Science.gov (United States)

Karaś-Ruszczyk, Katarzyna; Kuczyńska, Julita; Sienkiewicz-Jarosz, Halina; Kurkowska-Jastrzębska, Iwona; Bienkowski, Przemyslaw; Restel, Magdalena; Samochowiec, Jerzy; Mierzejewski, Pawel

2017-06-01

Previous findings revealed high correlations between serum/plasma and saliva levetiracetam concentrations, indicating saliva as an alternative matrix for monitoring levetiracetam therapy. Levetiracetam concentration in the hair, which could reflect long-term drug exposure and patients' compliance, has not been systematically tested, as yet. The aim of this study was to determine the correlation between plasma, saliva, and hair levetiracetam concentrations in 47 patients with epilepsy. Plasma, saliva, and hair levetiracetam concentrations were measured by liquid chromatography-tandem mass spectrometry with positive ionization. Levetiracetam saliva and plasma concentrations were highly correlated (r = 0.93). Plasma concentrations were not influenced by sex, age, and other concomitant antiepileptic drugs. Levetiracetam hair concentrations correlated with plasma concentrations (r = 0.36) but not daily dose (mg/kg). Drug hair concentrations were not influenced by hair color or treatment (dyed). The results tend to indicate that saliva may be a reliable alternative to plasma for monitoring levetiracetam concentrations. Levetiracetam can also be detected in human hair.

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

Science.gov (United States)

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

2014-01-01

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

Evaluation of a method for determining concentrations of isoeugenol, an AQUI-S residue, in fillet tissue from freshwater fish species.

Science.gov (United States)

Meinertz, Jeffery R; Schreier, Theresa M; Bernardy, Jeffry A

2008-01-01

AQUI-S is a fish anesthetic/sedative that is approved for use in a number of countries throughout the world and has the potential for use in the United States. The active ingredient in AQUI-S is isoeugenol. A method for determining isoeugenol concentrations in edible fillet tissue is needed for regulatory purposes, including surveillance and potential use in studies fulfilling human food safety data requirements if U.S. Food and Drug Administration approval is pursued. A method was developed and evaluated for determining isoeugenol concentrations in fillet tissue using relatively common procedures and equipment. The method produced accurate and precise results with fillet tissue from 10 freshwater fish species. The percentage of isoeugenol recovered from samples fortified with isoeugenol at nominal concentrations of 1, 50, and 100 microg/g for all species was always >80 and fillet tissue containing biologically incurred isoeugenol was fillet tissue extracts from 9 of the 10 species. The method detection limits for all but one species ranged from 0.004 to 0.014 microg/g, and the quantitation limits ranged from 0.012 to 0.048 microg/g.

Effect of intravenous drug administration mode on drug distribution in a tumor slab: a finite Fourier transform analysis.

Science.gov (United States)

Subramaniam, B; Claudius, J S

1990-03-08

Cancer therapy using chemotherapeutic drugs frequently involves injection of the drug into the body through some intravenous mode of administration, viz, continuous (drip) infusion or single/multiple bolus injection(s). An understanding of the effect of the various modes of administration upon tumor penetration of drug is essential to rational design of drug therapy. This paper investigates drug penetration into a model tumor of slab geometry (between two capillaries) in which the overall transport rate of drug is limited by intra-tumor transport characterized by an effective diffusion coefficient. Employing the method of Finite Fourier Transforms (FFT), analytical solutions have been obtained for transient drug distribution in both the plasma and the tumor following three modes of administration, viz, continuous infusion, single bolus injection and equally-spaced equal-dose multiple bolus injections, of a given amount of drug. The qualitative trends exhibited by the plasma drug distribution profiles are consistent with reported experimental studies. Two concepts, viz, the dimensionless decay constant and the plasma/tumor drug concentration trajectories, are found to be particularly useful in the rational design of drug therapy. The dimensionless decay constant provides a measure of the rate of drug decay in the plasma relative to the rate of drug diffusion into the tumor and is thus characteristic of the tumor/drug system. The magnitude of this parameter dictates the choice of drug administration mode for minimizing drug decay in the plasma while simultaneously maximizing drug transport into the tumor. The concentration trajectories provide a measure of the plasma drug concentration relative to the tumor drug concentration at various times following injection. When the tumor drug concentration exceeds the plasma drug concentration, the drug will begin to diffuse out of the tumor. Knowledge of the time at which this diffusion reversal occurs is especially useful

Distribution and persistence of the anti sea-lice drug teflubenzuron in wild fauna and sediments around a salmon farm, following a standard treatment

International Nuclear Information System (INIS)

Samuelsen, Ole B.; Lunestad, Bjørn T.; Hannisdal, Rita; Bannister, Raymond; Olsen, Siri; Tjensvoll, Tore; Farestveit, Eva; Ervik, Arne

2015-01-01

The salmon louse (Lepeoptheirus salmonis) is a challenge in the farming of Atlantic salmon (Salmo salar). To treat an infestation, different insecticides are used like the orally administered chitin synthetase inhibitor teflubenzuron. The concentrations and distribution of teflubenzuron were measured in water, organic particles, marine sediment and biota caught in the vicinity of a fish farm following a standard medication. Low concentrations were found in water samples whereas the organic waste from the farm, collected by sediment traps had concentrations higher than the medicated feed. Most of the organic waste was distributed to the bottom close to the farm but organic particles containing teflubenzuron were collected 1100 m from the farm. The sediment under the farm consisted of 5 to 10% organic material and therefore the concentration of teflubenzuron was much lower than in the organic waste. Teflubenzuron was persistent in the sediment with a stipulated halflife of 170 days. Sediment consuming polychaetes had high but decreasing concentrations of teflubenzuron throughout the experimental period, reflecting the decrease of teflubenzuron in the sediment. During medication most wild fauna contained teflubenzuron residues and where polychaetes and saith had highest concentrations. Eight months later only polychaetes and some crustaceans contained drug residues. What dosages that induce mortality in various crustaceans following short or long-term exposure is not known but the results indicate that the concentrations in defined individuals of king crab, shrimp, squat lobster and Norway lobster were high enough shortly after medication to induce mortality if moulting was imminent. Considering food safety, saith and the brown meat of crustaceans contained at first sampling concentrations of teflubenzuron higher than the MRL-value set for Atlantic salmon. The concentrations were, however, moderate and the amount of saith fillet or brown meat of crustaceans to be

Distribution and persistence of the anti sea-lice drug teflubenzuron in wild fauna and sediments around a salmon farm, following a standard treatment

Energy Technology Data Exchange (ETDEWEB)

Samuelsen, Ole B. [Institute of Marine Research, P.O. Box 1870 Nordnes, N-5817 Bergen (Norway); Lunestad, Bjørn T.; Hannisdal, Rita [National Institute of Nutrition and Seafood Research, P.O. Box 2029 Nordnes, N-5817 Bergen (Norway); Bannister, Raymond; Olsen, Siri [Institute of Marine Research, P.O. Box 1870 Nordnes, N-5817 Bergen (Norway); Tjensvoll, Tore [National Institute of Nutrition and Seafood Research, P.O. Box 2029 Nordnes, N-5817 Bergen (Norway); Farestveit, Eva; Ervik, Arne [Institute of Marine Research, P.O. Box 1870 Nordnes, N-5817 Bergen (Norway)

2015-03-01

The salmon louse (Lepeoptheirus salmonis) is a challenge in the farming of Atlantic salmon (Salmo salar). To treat an infestation, different insecticides are used like the orally administered chitin synthetase inhibitor teflubenzuron. The concentrations and distribution of teflubenzuron were measured in water, organic particles, marine sediment and biota caught in the vicinity of a fish farm following a standard medication. Low concentrations were found in water samples whereas the organic waste from the farm, collected by sediment traps had concentrations higher than the medicated feed. Most of the organic waste was distributed to the bottom close to the farm but organic particles containing teflubenzuron were collected 1100 m from the farm. The sediment under the farm consisted of 5 to 10% organic material and therefore the concentration of teflubenzuron was much lower than in the organic waste. Teflubenzuron was persistent in the sediment with a stipulated halflife of 170 days. Sediment consuming polychaetes had high but decreasing concentrations of teflubenzuron throughout the experimental period, reflecting the decrease of teflubenzuron in the sediment. During medication most wild fauna contained teflubenzuron residues and where polychaetes and saith had highest concentrations. Eight months later only polychaetes and some crustaceans contained drug residues. What dosages that induce mortality in various crustaceans following short or long-term exposure is not known but the results indicate that the concentrations in defined individuals of king crab, shrimp, squat lobster and Norway lobster were high enough shortly after medication to induce mortality if moulting was imminent. Considering food safety, saith and the brown meat of crustaceans contained at first sampling concentrations of teflubenzuron higher than the MRL-value set for Atlantic salmon. The concentrations were, however, moderate and the amount of saith fillet or brown meat of crustaceans to be

Removal of cytostatic drugs from aquatic environment: A review

Energy Technology Data Exchange (ETDEWEB)

Zhang, Jiefeng [Division of Environmental and Water Resources, School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Chang, Victor W.C., E-mail: wcchang@ntu.edu.sg [Division of Environmental and Water Resources, School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Giannis, Apostolos [Residues and Resource Reclamation Centre (R3C), Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, CleanTech One, Singapore 637141 (Singapore); Wang, Jing-Yuan [Division of Environmental and Water Resources, School of Civil and Environmental Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798 (Singapore); Residues and Resource Reclamation Centre (R3C), Nanyang Environment and Water Research Institute, Nanyang Technological University, 1 Cleantech Loop, CleanTech One, Singapore 637141 (Singapore)

2013-02-15

Cytostatic drugs have been widely used for chemotherapy for decades. However, many of them have been categorized as carcinogenic, mutagenic and teratogenic compounds, triggering widespread concerns about their occupational exposure and ecotoxicological risks to the environment. This review focuses on trace presence, fate and ecotoxicity of various cytostatic compounds in the environment, with an emphasis on the major sources contributing to their environmental concentrations. Past records have documented findings mainly on hospital effluents though little effort has been directed to household discharges. There is also a lack in physico-chemical data for forecasting the chemodynamics of cytostatics in natural waters along with its human metabolites and environmental transformation products. In this light, obtaining comprehensive ecotoxicity data is becoming pressingly crucial to determine their actual impacts on the ecosystem. Literature review also reveals urinary excretion as a major contributor to various cytostatic residues appeared in the water cycle. As such, engaging urine source-separation as a part of control strategy holds a rosy prospect of addressing the “emerging” contamination issue. State-of-the-art treatment technologies should be incorporated to further remove cytostatic residues from the source-separating urine stream. The benefits, limitations and trends of development in this domain are covered for membrane bio-reactor, reverse/forward osmosis and advanced oxidation processes. Despite the respective seeming advantages of source separation and treatment technology, a combined strategy may cost-effectively prevent the cytostatic residues from seeping into the environment. However, the combination calls for further evaluation on the associated technological, social-economic and administrative issues at hand. Highlights: ► We review the environmental occurrence, fate and ecotoxicity of cytostatic drugs. ► Four major sources contributing to

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

NARCIS (Netherlands)

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

2016-01-01

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

Optimization of Drug Delivery by Drug-Eluting Stents.

Directory of Open Access Journals (Sweden)

Franz Bozsak

Full Text Available Drug-eluting stents (DES, which release anti-proliferative drugs into the arterial wall in a controlled manner, have drastically reduced the rate of in-stent restenosis and revolutionized the treatment of atherosclerosis. However, late stent thrombosis remains a safety concern in DES, mainly due to delayed healing of the endothelial wound inflicted during DES implantation. We present a framework to optimize DES design such that restenosis is inhibited without affecting the endothelial healing process. To this end, we have developed a computational model of fluid flow and drug transport in stented arteries and have used this model to establish a metric for quantifying DES performance. The model takes into account the multi-layered structure of the arterial wall and incorporates a reversible binding model to describe drug interaction with the cells of the arterial wall. The model is coupled to a novel optimization algorithm that allows identification of optimal DES designs. We show that optimizing the period of drug release from DES and the initial drug concentration within the coating has a drastic effect on DES performance. Paclitaxel-eluting stents perform optimally by releasing their drug either very rapidly (within a few hours or very slowly (over periods of several months up to one year at concentrations considerably lower than current DES. In contrast, sirolimus-eluting stents perform optimally only when drug release is slow. The results offer explanations for recent trends in the development of DES and demonstrate the potential for large improvements in DES design relative to the current state of commercial devices.

Evaluation of Crops Sensitivity to Atrazine Soil Residual

Directory of Open Access Journals (Sweden)

E Izadi

2012-02-01

Full Text Available Abstract In order to study the sensitivity of 9 crops to atrazine soil residual, two separate experiments were conducted in field and greenhouse conditions. First experiment was conducted in a field with treated soil by atrazine based on split plot and the results evaluated in greenhouse conditions. Treatments in the field experiment included two organic manure application rates (0 and 50 t/ha as main plots and 2 atrazine application rates (2 and 4 kg/ha atrazine a.i. as sob plots. After corn harvesting soil was sampled at 0-15 cm surface layer in each plots in 15 points, after mixing the samples. Wheat, barley, sugar beet, pea, lens and colza planted in pots at greenhouse. Second experiment conducted in greenhouse conditions for evaluation of atrazine soil residual in completely randomized design. Treatments included atrazine soil residual concentrations (0, 0.2, 0.5, 1, 5, 10 and 15 mg/kg soil and crops included wheat, barley, sugar beet, pea, lens, rape, bean and tomato. Results showed that atrazine residue had no effect on crops growth in field experiment treated with atrazine. It seems that atrazine residue in filed soil is lower that its damage threshold for crops or maybe for its fast removal in field than in control conditions. But in bioassay experiment (greenhouse experiment crops response to atrazine residues were different. Results showed that onion and pea were most susceptible ant tolerant crops between studied species and based of ED50 parameter the other crops tolerance to total residue ranked as: pea< bean< lentil< sugar beet< tomato< barley< wheat< rape< onion. Keywords: Atrazine residue, Pea, Bean, Lentil, Sugar beet, Barley, Wheat, Rape, Tomato

Pharmacokinetic-Pharmacodynamic (PKPD) Analysis with Drug Discrimination.

Science.gov (United States)

Negus, S Stevens; Banks, Matthew L

2016-08-30

Discriminative stimulus and other drug effects are determined by the concentration of drug at its target receptor and by the pharmacodynamic consequences of drug-receptor interaction. For in vivo procedures such as drug discrimination, drug concentration at receptors in a given anatomical location (e.g., the brain) is determined both by the dose of drug administered and by pharmacokinetic processes of absorption, distribution, metabolism, and excretion that deliver drug to and from that anatomical location. Drug discrimination data are often analyzed by strategies of dose-effect analysis to determine parameters such as potency and efficacy. Pharmacokinetic-Pharmacodynamic (PKPD) analysis is an alternative to conventional dose-effect analysis, and it relates drug effects to a measure of drug concentration in a body compartment (e.g., venous blood) rather than to drug dose. PKPD analysis can yield insights on pharmacokinetic and pharmacodynamic determinants of drug action. PKPD analysis can also facilitate translational research by identifying species differences in pharmacokinetics and providing a basis for integrating these differences into interpretation of drug effects. Examples are discussed here to illustrate the application of PKPD analysis to the evaluation of drug effects in rhesus monkeys trained to discriminate cocaine from saline.

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

Science.gov (United States)

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

2012-11-05

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

Thermal and long-term freezing stability of ivermectin residues in sheep milk

NARCIS (Netherlands)

Cerkvenik, V.; Doganoc, D.Z.; Skubic, V.; Beek, W.M.J.; Keukens, H.J.

2001-01-01

The stability of ivermectin residues in sheep milk under conditions of pasteurization (74 °C, 40 s), high pasteurization (80 °C, 1 min), and boiling (100 °C, 10 s) based on residue content (at a level of concentration of about 2 ?g/kg and 30 ?g/kg of H2B1a) and sort of ingestion (in vitro, in vivo)

Sustainable System for Residual Hazards Management

International Nuclear Information System (INIS)

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

2004-01-01

Hazardous, radioactive and other toxic substances have routinely been generated and subsequently disposed of in the shallow subsurface throughout the world. Many of today's waste management techniques do not eliminate the problem, but rather only concentrate or contain the hazardous contaminants. Residual hazards result from the presence of hazardous and/or contaminated material that remains on-site following active operations or the completion of remedial actions. Residual hazards pose continued risk to humans and the environment and represent a significant and chronic problem that require continuous long-term management (i.e. >1000 years). To protect human health and safeguard the natural environment, a sustainable system is required for the proper management of residual hazards. A sustainable system for the management of residual hazards will require the integration of engineered, institutional and land-use controls to isolate residual contaminants and thus minimize the associated hazards. Engineered controls are physical modifications to the natural setting and ecosystem, including the site, facility, and/or the residual materials themselves, in order to reduce or eliminate the potential for exposure to contaminants of concern (COCs). Institutional controls are processes, instruments, and mechanisms designed to influence human behavior and activity. System failure can involve hazardous material escaping from the confinement because of system degradation (i.e., chronic or acute degradation) or by external intrusion of the biosphere into the contaminated material because of the loss of institutional control. An ongoing analysis of contemporary and historic sites suggests that the significance of the loss of institutional controls is a critical pathway because decisions made during the operations/remedial action phase, as well as decisions made throughout the residual hazards management period, are key to the long-term success of the prescribed system. In fact

The effect of delignification process with alkaline peroxide on lactic acid production from furfural residues

Directory of Open Access Journals (Sweden)

Yong Tang

2012-11-01

Full Text Available Furfural residues produced from the furfural industry were investigated as a substrate for lactic acid production by simultaneous saccharification and fermentation (SSF. Alkaline peroxide was used for delignification of furfural residues to improve the final lactic acid concentration. The residue was treated with 1.3% to 1.7% hydrogen peroxide at 80 °C for 1 h with a substrate concentration of 3.33%. SSF of furfural residues with different delignification degrees were carried out to evaluate the effect of delignification degree on lactic acid production. Using corn hydrolysates/ furfural residues as substrates, SSF with different media were carried out to investigate the effect of lignin on the interaction between enzymes and lactic acid bacteria. Lactic acid bacteria had a negative effect on cellulase, thus resulting in the reduction of enzyme activity. Lignin and nutrients slowed down the decreasing trend of enzyme activity. A higher delignification resulted in a slower fermentation rate and lower yield due to degradation products of lignin and the effect of lignin on the interaction between enzymes and lactic acid bacteria. For the purpose of lactic acid production, a moderate delignification (furfural residues with the lignin content of 14.8% was optimum.

Vaginal drug distribution modeling.

Science.gov (United States)

Katz, David F; Yuan, Andrew; Gao, Yajing

2015-09-15

This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it. Copyright © 2015 Elsevier B.V. All rights reserved.

Analysis of residual chlorine in simple drinking water distribution system with intermittent water supply

Science.gov (United States)

Goyal, Roopali V.; Patel, H. M.

2015-09-01

Knowledge of residual chlorine concentration at various locations in drinking water distribution system is essential final check to the quality of water supplied to the consumers. This paper presents a methodology to find out the residual chlorine concentration at various locations in simple branch network by integrating the hydraulic and water quality model using first-order chlorine decay equation with booster chlorination nodes for intermittent water supply. The explicit equations are developed to compute the residual chlorine in network with a long distribution pipe line at critical nodes. These equations are applicable to Indian conditions where intermittent water supply is the most common system of water supply. It is observed that in intermittent water supply, the residual chlorine at farthest node is sensitive to water supply hours and travelling time of chlorine. Thus, the travelling time of chlorine can be considered to justify the requirement of booster chlorination for intermittent water supply.

MICROBIOLOGICAL EVALUATION OF ANTIBIOTIC RESIDUES IN MEAT, MILK AND EGGS

Directory of Open Access Journals (Sweden)

Abdul Jabbar

2013-04-01

Full Text Available Microbiological tests are widely used to detect antibiotic residues in the meat, milk and eggs for better care of the quality and health safety. In the present study microbiological inhibition test i.e. Swab Test on Animal Food (STAF was developed indigenously for screening of animal foods for presence of antibiotic residues. In this test local isolated culture of Bacillus subtilis was used as a test microorganism due to its high sensitivity to detect a wide range of antibiotics commonly used in animal disorders. The concentration of spore suspension of Bacillus subtilis JS2004 used in the formation of STAF plate was optimized at 2x107 spores/ ml. At this concentration, inhibition zone around Neomycin control disc was 10-16 mm. Nutrient agar was used as a medium in spore suspension and 0.4% dextrose was added as a constituent of medium. Zones of inhibition around swab samples and Neomycin control disc were observed and the diameter was measured. All swab samples showing a minimum of 2 mm wide inhibition zone around them were considered as positive for presence of antibiotic residues. The swab samples showing no zone of inhibition or a zone measuring less than 2 mm were considered as negative. Results of application of STAF test was on animal food samples revealed the high incidence of antibiotic residues.

DDT residues in sediments from the Bay of Bengal

Digital Repository Service at National Institute of Oceanography (India)

Sarkar, A.; SenGupta, R.

in the sediments from the Bay of Bengal. Peterson grab and hydrographic winch was used to collect the sediment samples. Each sample was extracted and cleaned. Residues were detected by electron capture gas chromatography. A range variation in the concentration...

Effect of Refining Processes on Magnitude and Nature of Malathion and Carbofuran Residues in Cotton Seed Oil

International Nuclear Information System (INIS)

Zayed, S.M.A.D.; Farghaly, M.; Mahdy, F.

2005-01-01

Cotton seeds obtained from 14 C-carbofuran or 14 C-malathion-treated plants contained 0.25% and 0.11% of the originally applied radioactivity, respectively. The concentration of malathion residues in oil, methanol soluble and in the seed cake amounted to 0.94, 2.6 and 1.7 ppm, respectively. Commercial processing procedures led to a gradual decrease in the total amount of 14 C-residues in oils with aged residues as well as in oil fortified with the radiolabelled insecticides. The refined oil contained only about 20% of the 14 C-residues originally present. The major residue in processed oil contained malathion, malathion monocarboxylic acid and alpha-(O,O-dimethyl phosphorodithio)-propionic acid. The concentration of 14 C-carbofuran residues in cotton seed oil, methanol extract and cake was 1.7, 12.3 and 2.4 ppm, respectively. The main residues in the oil were carbofuran and its phenol. The methanol solubles contained conjugated metabolites, which upon hydrolysis gave 3-hydroxy-carbofuran as a major product. Refinement reduced the residue in oil to 0.26 ppm. The residue in refined oil contained carbofuran and carbofuran phenol as main constituents together with smaller amounts of 3-hydroxy- and 3-keto carbofuran

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

Directory of Open Access Journals (Sweden)

Donghee Park

Full Text Available Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with

Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

Science.gov (United States)

Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

2016-01-01

Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the

Residual stresses

International Nuclear Information System (INIS)

Sahotra, I.M.

2006-01-01

The principal effect of unloading a material strained into the plastic range is to create a permanent set (plastic deformation), which if restricted somehow, gives rise to a system of self-balancing within the same member or reaction balanced by other members of the structure., known as residual stresses. These stresses stay there as locked-in stresses, in the body or a part of it in the absence of any external loading. Residual stresses are induced during hot-rolling and welding differential cooling, cold-forming and extruding: cold straightening and spot heating, fabrication and forced fitting of components constraining the structure to a particular geometry. The areas which cool more quickly develop residual compressive stresses, while the slower cooling areas develop residual tensile stresses, and a self-balancing or reaction balanced system of residual stresses is formed. The phenomenon of residual stresses is the most challenging in its application in surface modification techniques determining endurance mechanism against fracture and fatigue failures. This paper discusses the mechanism of residual stresses, that how the residual stresses are fanned and what their behavior is under the action of external forces. Such as in the case of a circular bar under limit torque, rectangular beam under limt moment, reclaiming of shafts welds and peening etc. (author)

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

Science.gov (United States)

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

2018-05-31

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

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

Science.gov (United States)

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

2017-06-02

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

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

Science.gov (United States)

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

2013-05-01

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

Effect of handling and processing on pesticide residues in food- a review.

Science.gov (United States)

Bajwa, Usha; Sandhu, Kulwant Singh

2014-02-01

Pesticides are one of the major inputs used for increasing agricultural productivity of crops. The pesticide residues, left to variable extent in the food materials after harvesting, are beyond the control of consumer and have deleterious effect on human health. The presence of pesticide residues is a major bottleneck in the international trade of food commodities. The localization of pesticides in foods varies with the nature of pesticide molecule, type and portion of food material and environmental factors. The food crops treated with pesticides invariably contain unpredictable amount of these chemicals, therefore, it becomes imperative to find out some alternatives for decontamination of foods. The washing with water or soaking in solutions of salt and some chemicals e.g. chlorine, chlorine dioxide, hydrogen peroxide, ozone, acetic acid, hydroxy peracetic acid, iprodione and detergents are reported to be highly effective in reducing the level of pesticides. Preparatory steps like peeling, trimming etc. remove the residues from outer portions. Various thermal processing treatments like pasteurization, blanching, boiling, cooking, steaming, canning, scrambling etc. have been found valuable in degradation of various pesticides depending upon the type of pesticide and length of treatment. Preservation techniques like drying or dehydration and concentration increase the pesticide content many folds due to concentration effect. Many other techniques like refining, fermentation and curing have been reported to affect the pesticide level in foods to varied extent. Milling, baking, wine making, malting and brewing resulted in lowering of pesticide residue level in the end products. Post harvest treatments and cold storage have also been found effective. Many of the decontamination techniques bring down the concentration of pesticides below MRL. However, the diminution effect depends upon the initial concentration at the time of harvest, substrate/food and type of

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

Science.gov (United States)

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.

Research of nitroxynil residues in bovine milk following a single administration in the dry period by ultra-performance liquid chromatography tandem mass spectrometry

Directory of Open Access Journals (Sweden)

Claudia Chirollo

2013-10-01

Full Text Available Nitroxynil (NIT is a halogenated phenol used to control fascioliasis in cattle and sheep. The Commission Regulation EU No 37/2010 has established maximum residue limits for NIT in bovine and ovine muscle (400 μg kg−1, fat (200 μg kg−1, liver (20 μg kg−1 and kidney (400 μg kg−1, and more recently in bovine and ovine milk (20 μg kg−1. Thirty-five pregnant dairy cows were treated in this study with nitroxynil (340 mg/mL solution for injection at the recommended dose of 10 mg/kg body weight at the start of the dry period, i.e. 53 to 74 days before the expected calving. Calving occurred between 43 days and 79 days after treatment. The concentrations of NIT in the milk were monitored for up to 120 days after calving. NIT residues were extracted using acetonitrile; magnesium sulfate and sodium chloride were added to induce liquid-liquid partitioning and purified by dispersive solid phase extraction for clean-up. NIT was detected by ultra high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS in negative ionization mode. The highest concentrations of this drug were found in two animals at the first milking, 48 and 53 day post treatment with levels of 362 and 657 μg kg–1, respectively. NIT residues were below the limit of detection of the method (0.24 μg/kg–1 between 67 and 106 day post-treatment. Following calving, residues rapidly depleted in animals and were non-detectable from 10 to 38 days post-calving. In particular, in all animals milk resulted compliant (<20 μg/kg−1 three days post partum.

Petroleum hydrocarbon residues in the marine environment of Bassein-Mumbai

International Nuclear Information System (INIS)

Chouksey, M.K.; Kadam, A.N.; Zingde, M.D.

2005-01-01

The paper reports PHc contamination in water, sediment and biota of the coastal area of Bassein-Mumbai in relation to relatively less polluted sites (Dabhol and Ratnagiri) off the west coast of India. To facilitate inter-comparison three standards have been used though the results are reported in terms of SAM (Residue of Saudi Arabian Mix crude). The concentration of PHc in water off Bassein-Mumbai varies widely (2.9-39.2 μg l -1 ) as compared to the average baseline (2.8 μgl -1 ) with higher values generally confined to creeks and estuaries. The higher concentration of PHc in the bottom water of shallow areas is attributed to the contribution from the sediment-associated petroleum residue. High concentration of PHc in the surficial sediment of inshore area Ratnagiri (107.7 ppm, dry wt) is perhaps the remnants of an oil spill that occurred in the Bombay High region on May 17, 1993. The majority of values of PHc concentration in the surficial sediment of the Bassein-Mumbai region exceed 15 ppm (dry wt) against the expected background ( -1 respectively is estimated for cores U11 and U12. Substantial increase in the concentration of PHc in sediment after 1950 in cores T8 and T10 correlates well with the establishment of refineries on the western shore of the Thane Creek in 1955-1960. A minor peak in most cores in the top 10 cm sediment probably results from biological transfer of PHc lower into the sediment by benthic organisms. Excess of PHc retained in the sediment of the Bassein-Mumbai region over the biogenic background is estimated at 40,000 t. The PHc residues (1.8-10.8 ppm, wet wt) in fish caught off Bassein-Mumbai do not suggest bioaccumulation. (author)

Levels of organochlorine pesticide residue in grasscutter (Thryonomys swinderianus) tissues

International Nuclear Information System (INIS)

Blankson-Arthur, S.

2009-06-01

Organochlorine pesticide residues have been determined in the muscle, liver and kidney tissues from a total of 45 grasscutter (Thryonomys swinderianus) meat samples obtained from the Gomoa district, a vegetable farming area in the Central Region of Ghana. All samples were analyzed for their residue content of the following organochlorine pesticides; DDT, DDE, hexachlorocyclohexane isomers, lindane (γ-HCH) and δ-HCH, dieldrin, aldrin, endrin, endrin aldehyde, endrin ketone, alpha endosulfan, endosulfan sulfate, chlordane, heptachlor and methoxychlor. The results indicated that all the analyzed samples were contaminated with the studied organochlorine pesticides. Aldrin and heptachlor were the principal contaminants in all the samples. The muscle had the highest pollutant load. All organochlorine pesticides investigated were detected in the muscle tissues of the grasscutter at the following mean concentrations; aldrin 1.833μg /kg, heptachlor 0.695μg /kg, γ-HCH 0.283μg /kg, δ-HCH 0.108μg /kg, dieldrin 0.040 μg /kg, p,p'-DDT 0.019μg /kg. p,p'-DDE 0.014μg /kg, endrin 0.018μg /kg, endrin aldehyde 0.090μg /kg, endrin ketone 0.340μg /kg, α-endosulfan 0.162μg /kg, endosulfan sulfate 0.183μg /kg, gamma-chlordane 0.174μg /kg and methoxychlor 0.101μg /kg wet weight. The organochlorine pesticide residues were detected in the liver tissues at the following mean concentrations; aldrin 1.315μg /kg, heptachlor 0.530μg /kg, dieldrin 0.050μg /kg, γ-HCH 0.233μg /kg, δ-HCH 0.070μg /kg, p,p'-DDT 0.123μg /kg. p,p'-DDE 0.043μg /kg endrin aldehyde 0.110μg /kg, endrin ketone 0.115μg /kg, gamma-chlordane 0.093μg /kg and methoxychlor 0.128μg /kg wet weight. No endrin was however detected in the liver. The highest concentrations of γ-HCH, δ-HCH, endrin ketone and endrin aldehyde were measured in the kidney. The mean concentrations of γ-HCH and δ-HCH in the kidney were 0.435μg /kg and 0.107μg /kg respectively. Endrin aldehyde was detected at 0.135μg /kg in

Exposure of the Public from Large Deposits of Mineral Residues

International Nuclear Information System (INIS)

2011-06-01

All minerals and raw materials contain radionuclides of natural origin. In most situations, the exposure of humans to such radionuclides is considered to be part of the normal natural radiation background and is not generally of concern. In some cases, however, the radionuclide concentrations are elevated above normal levels or become elevated as a result of mineral processing activities, and measures for protecting against exposure to the material involved may need to be considered. The mineral or raw material is then treated as radioactive material for the purposes of radiation protection and falls within the definition of naturally occurring radioactive material (NORM). The IAEA has developed criteria for determining which materials need to be considered for regulatory control. For materials containing only radionuclides of natural origin, the criteria are an activity concentration of 1 Bq/g for 238 U, 235 U, 232 Th and their decay progeny and an activity concentration of 10 Bq/g for 40 K. These values were determined on the basis of the activity concentrations of these radionuclides in normal rocks and soil, and represent the (rounded) upper bounds of the ranges of such concentrations as determined by the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR). The values are intended to apply to all solid materials except foodstuffs, material in transport and radioactive residues in the environment (for which separate criteria apply) and 40 K in the body (which is excluded entirely from regulatory requirements). While the radiation dose was not a consideration in the determination of the above-mentioned regulatory criteria, the IAEA has noted that doses received by individuals as a consequence of the use of these criteria are unlikely to exceed about 1 mSv in a year, excluding the emanation of radon. However, in the case of bulk volumes of material contaminating water pathways, such as large deposits of NORM residues from mining and

Disruption of key NADH-binding pocket residues of the Mycobacterium tuberculosis InhA affects DD-CoA binding ability.

Science.gov (United States)

Shaw, Daniel J; Robb, Kirsty; Vetter, Beatrice V; Tong, Madeline; Molle, Virginie; Hunt, Neil T; Hoskisson, Paul A

2017-07-05

Tuberculosis (TB) is a global health problem that affects over 10 million people. There is an urgent need to develop novel antimicrobial therapies to combat TB. To achieve this, a thorough understanding of key validated drug targets is required. The enoyl reductase InhA, responsible for synthesis of essential mycolic acids in the mycobacterial cell wall, is the target for the frontline anti-TB drug isoniazid. To better understand the activity of this protein a series of mutants, targeted to the NADH co-factor binding pocket were created. Residues P193 and W222 comprise a series of hydrophobic residues surrounding the cofactor binding site and mutation of both residues negatively affect InhA function. Construction of an M155A mutant of InhA results in increased affinity for NADH and DD-CoA turnover but with a reduction in V max for DD-CoA, impairing overall activity. This suggests that NADH-binding geometry of InhA likely permits long-range interactions between residues in the NADH-binding pocket to facilitate substrate turnover in the DD-CoA binding region of the protein. Understanding the precise details of substrate binding and turnover in InhA and how this may affect protein-protein interactions may facilitate the development of improved inhibitors enabling the development of novel anti-TB drugs.

Spray-on transdermal drug delivery systems.

Science.gov (United States)

Ibrahim, Sarah A

2015-02-01

Transdermal drug delivery possesses superior advantages over other routes of administration, particularly minimizing first-pass metabolism. Transdermal drug delivery is challenged by the barrier nature of skin. Numerous technologies have been developed to overcome the relatively low skin permeability, including spray-on transdermal systems. A transdermal spray-on system (TSS) usually consists of a solution containing the drug, a volatile solvent and in many cases a chemical penetration enhancer. TSS promotes drug delivery via the complex interplay between solvent evaporation and drug-solvent drag into skin. The volatile solvent carries the drug into the upper layers of the stratum corneum, and as the volatile solvent evaporates, an increase in the thermodynamic activity of the drug occurs resulting in an increased drug loading in skin. TSS is easily applied, delivering flexible drug dosage and associated with lower incidence of skin irritation. TSS provides a fast-drying product where the volatile solvent enables uniform drug distribution with minimal vehicle deposition on skin. TSS ensures precise dose administration that is aesthetically appealing and eliminates concerns of residual drug associated with transdermal patches. Furthermore, it provides a better alternative to traditional transdermal products due to ease of product development and manufacturing.

A REVIEW ON OSMOTIC DRUG DELIVERY SYSTEM

OpenAIRE

Harnish Patel; Upendra Patel; Hiren Kadikar; Bhavin Bhimani; Dhiren Daslaniya; Ghanshyam Patel

2012-01-01

Conventional oral drug delivery systems supply an instantaneous release of drug, which cannot control the release of the drug and effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable con...

Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.

Directory of Open Access Journals (Sweden)

Aylin Yilmaz

2009-09-01

Full Text Available Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF and plasma in subjects receiving antiretroviral treatment regimens containing this drug.Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma.Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0-126.0. The median plasma raltegravir concentration was 448 ng/ml (range, 37-5180. CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations.Approximately 50% of the CSF specimens exceeded the IC(95 levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry.

Raltegravir cerebrospinal fluid concentrations in HIV-1 infection.

Science.gov (United States)

Yilmaz, Aylin; Gisslén, Magnus; Spudich, Serena; Lee, Evelyn; Jayewardene, Anura; Aweeka, Francesca; Price, Richard W

2009-09-01

Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing this drug. Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma. Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0-126.0). The median plasma raltegravir concentration was 448 ng/ml (range, 37-5180). CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations. Approximately 50% of the CSF specimens exceeded the IC(95) levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry.

[Effects of rice cleaning and cooking process on the residues of flutolanil, fenobucarb, silafluofen and buprofezin in rice].

Science.gov (United States)

Satoh, Motoaki; Sakaguchi, Masayuki; Kobata, Masakazu; Sakaguchi, Yoko; Tanizawa, Haruna; Miura, Yuri; Sasano, Ryoichi; Nakanishi, Yutaka

2003-02-01

We studied the effect of cleaning and cooking on the residues of flutolanil, fenobucarb, silafluofen and buprofezin in rice. The rice had been sprayed in a paddy field in Wakayama city, with 3 kinds of pesticide application protocols: spraying once at the usual concentration of pesticides, repeated spraying (3 times) with the usual concentration of pesticides and spraying once with 3 times the usual concentration of pesticides. The residue levels of pesticide decreased during the rice cleaning process. Silafluofen, which has a higher log Pow value, remained in the hull of the rice. Fenobucarb, which has a lower log Pow value, penetrated inside the rice. The residue concentration of pesticide in polished rice was higher than that in pre-washed rice processed ready for cooking. During the cooking procedure, the reduction of pesticides in polished rice was higher than that in brown rice.