WorldWideScience

Sample records for perfluoroalkyl sulfonamide generic

  1. A survey of perfluoroalkyl sulfonamides in indoor and outdoor air using passive air samplers

    Energy Technology Data Exchange (ETDEWEB)

    Shoeib, M.; Harner, T. [Meteorological Service of Canada, Environment Canada (Canada); Wilford, B.; Jones, K. [Lancaster Univ. (United Kingdom). Environmental Science; Zhu, J. [Chemistry Research Division, Health Canada, Tunney' s Pasture, Ottawa (Canada)

    2004-09-15

    Perfluorooctane sulfonate (PFOS) has recently emerged as a priority environmental pollutant due to its widespread detection in biological samples from remote regions including the Arctic and the Mid-North Pacific Ocean. Because PFOS is fairly involatile, it is hypothesized that its occurrence in remote regions is the result of atmospheric transport of more volatile precursor compounds such as the perfluoroalkyl sulfonamides (PFASs). PFASs are used in variety of consumer products for water and oil resistance including surface treatments for fabric, upholstery, carpet, paper and leather. In a recent pilot study employing high volume air samples, indoor air concentrations of PFASs were approximately 100 times greater than outdoor levels. This is of significance because people typically spend about 90% of their time indoors 5 and this exposure may serve as an important uptake pathway. Indoor air also serves as a source of PFASs to the outside where PFASs are ultimately transported and distributed throughout the environment. The current study is intended to be a more comprehensive survey of indoor and outdoor air allowing more confident conclusions to be made. Passive air samplers comprised of polyurethane foam (PUF) disks were used. These are quiet, non-intrusive samplers that operate without the aid of a pump or electricity. Air movement delivers chemical to the sampler which has a high retention capacity for persistent organic pollutants (POPs). PUF disks samplers have been previously used successfully to monitor different classes of hydrophobic persistent organic pollutants POPs.

  2. A generic approach for expanding homolog-targeted residue screening of sulfonamides using a fast matrix separation and class-specific fragmentation-dependent acquisition with a hybrid quadrupole-linear ion trap mass spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Huang Chunlin [Department of Biochemistry and Molecular Biology, School of Pharmacy and Life Science, University of South China, Hengyang 421001 (China); Guo Bin, E-mail: binnguo@126.com [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081 (China); Wang Xiaoying [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081 (China); Li Jie [Department of Biochemistry and Molecular Biology, School of Pharmacy and Life Science, University of South China, Hengyang 421001 (China); Zhu Weitao; Chen Bo [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081 (China); Ouyang Shan [Food Inspection and Quarantine Center, Shenzhen Entry-Exit Inspection and Quarantine Bureau of the People' s Republic of China, Shenzhen 518067 (China); Yao Shouzhuo [Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research (Ministry of Education of China), Hunan Normal University, Changsha 410081 (China)

    2012-08-06

    Highlights: Black-Right-Pointing-Pointer Generic homolog-targeted screening approach for multi-residual sulfonamide analogs. Black-Right-Pointing-Pointer Single-tube extraction/partitioning-multifunction adsorption cleanup for direct injection. Black-Right-Pointing-Pointer Class-specific fragmentation for expanding coverage of N{sup 4}-acetyl and N-OH metabolites. Black-Right-Pointing-Pointer PreS-IDA-EPI in LC-QqLIT for simultaneous screening and confirmation of real samples. - Abstract: A generic and efficient homolog-targeted approach was used to expand screening and detection of target class of sulfonamides and structural analogs, based on a fast single-tube extraction/partitioning-multifunction adsorption cleanup (SEP/MAC) for class-specific fragmentation-dependent acquisition with a liquid chromatography-hybrid triple-quadrupole linear ion trap mass spectrometer (LC-QqLIT). By combining the two-stage process conducted in a single tube as one-pot protocol, the straightforward SEP/MAC procedure was optimized to offer clean extracts with reasonable recovery (71-109% with RSDs < 20%) and decreased matrix interferences (-9 to 19%) of multiresidual sulfonamide extraction from different tissue samples. The novel use of neutral loss scan of 66 Da (NLS) or precursor ion scanning of m/z 108 (PreS) in positive ion mode was found to achieve more comprehensive coverage of protonated molecular ions of a wide array of sulfonamides including N{sup 4}-acetyl and hydroxylamine metabolites plus their possible dimers. Moreover, the PreS-triggered automatically enhanced product ion spectral acquisition enabled simultaneous screening, profiling and confirmation of an unlimited number of analytes belonging to the sulfonamide class within a single analysis. The validation and application results of the generic SEP/MAC-based LC-QqLIT strategy consistently demonstrated favorable performances with acceptable accuracy (67-116%), precision (RSDs < 25%), and sensitivity (LOQs {<=} 7.5 ng

  3. A generic approach for expanding homolog-targeted residue screening of sulfonamides using a fast matrix separation and class-specific fragmentation-dependent acquisition with a hybrid quadrupole-linear ion trap mass spectrometer

    International Nuclear Information System (INIS)

    Huang Chunlin; Guo Bin; Wang Xiaoying; Li Jie; Zhu Weitao; Chen Bo; Ouyang Shan; Yao Shouzhuo

    2012-01-01

    Highlights: ► Generic homolog-targeted screening approach for multi-residual sulfonamide analogs. ► Single-tube extraction/partitioning-multifunction adsorption cleanup for direct injection. ► Class-specific fragmentation for expanding coverage of N 4 -acetyl and N-OH metabolites. ► PreS–IDA–EPI in LC–QqLIT for simultaneous screening and confirmation of real samples. - Abstract: A generic and efficient homolog-targeted approach was used to expand screening and detection of target class of sulfonamides and structural analogs, based on a fast single-tube extraction/partitioning-multifunction adsorption cleanup (SEP/MAC) for class-specific fragmentation-dependent acquisition with a liquid chromatography–hybrid triple-quadrupole linear ion trap mass spectrometer (LC–QqLIT). By combining the two-stage process conducted in a single tube as one-pot protocol, the straightforward SEP/MAC procedure was optimized to offer clean extracts with reasonable recovery (71–109% with RSDs 4 -acetyl and hydroxylamine metabolites plus their possible dimers. Moreover, the PreS-triggered automatically enhanced product ion spectral acquisition enabled simultaneous screening, profiling and confirmation of an unlimited number of analytes belonging to the sulfonamide class within a single analysis. The validation and application results of the generic SEP/MAC-based LC–QqLIT strategy consistently demonstrated favorable performances with acceptable accuracy (67–116%), precision (RSDs −1 ) to meet the acceptance criteria for all the sulfonamide–tissue combinations. Thus, the integration of the matrix-independent SEP/MAC procedure and the multiparameter matching algorithm with the unit-resolution LC–QqLIT instrument can serve as a valuable semi-targeted discovery strategy for rapid screening and reliable quantitative/confirmatory analysis of real samples.

  4. Sulfonamidation of Aryl and Heteroaryl Halides through Photosensitized Nickel Catalysis.

    Science.gov (United States)

    Kim, Taehoon; McCarver, Stefan J; Lee, Chulbom; MacMillan, David W C

    2018-03-19

    Herein we report a highly efficient method for nickel-catalyzed C-N bond formation between sulfonamides and aryl electrophiles. This technology provides generic access to a broad range of N-aryl and N-heteroaryl sulfonamide motifs, which are widely represented in drug discovery. Initial mechanistic studies suggest an energy-transfer mechanism wherein C-N bond reductive elimination occurs from a triplet excited Ni II complex. Late-stage sulfonamidation in the synthesis of a pharmacologically relevant structure is also demonstrated. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Perfluoroalkylated substances in the global tropical and subtropical surface oceans.

    Science.gov (United States)

    González-Gaya, Belén; Dachs, Jordi; Roscales, Jose L; Caballero, Gemma; Jiménez, Begoña

    2014-11-18

    In this study, perfluoroalkylated substances (PFASs) were analyzed in 92 surface seawater samples taken during the Malaspina 2010 expedition which covered all the tropical and subtropical Atlantic, Pacific and Indian oceans. Nine ionic PFASs including C6-C10 perfluoroalkyl carboxylic acids (PFCAs), C4 and C6-C8 perfluoroalkyl sulfonic acids (PFSAs) and two neutral precursors perfluoroalkyl sulfonamides (PFASAs), were identified and quantified. The Atlantic Ocean presented the broader range in concentrations of total PFASs (131-10900 pg/L, median 645 pg/L, n = 45) compared to the other oceanic basins, probably due to a better spatial coverage. Total concentrations in the Pacific ranged from 344 to 2500 pg/L (median = 527 pg/L, n = 27) and in the Indian Ocean from 176 to 1976 pg/L (median = 329, n = 18). Perfluorooctanesulfonic acid (PFOS) was the most abundant compound, accounting for 33% of the total PFASs globally, followed by perfluorodecanoic acid (PFDA, 22%) and perfluorohexanoic acid (PFHxA, 12%), being the rest of the individual congeners under 10% of total PFASs, even for perfluorooctane carboxylic acid (PFOA, 6%). PFASAs accounted for less than 1% of the total PFASs concentration. This study reports the ubiquitous occurrence of PFCAs, PFSAs, and PFASAs in the global ocean, being the first attempt, to our knowledge, to show a comprehensive assessment in surface water samples collected in a single oceanic expedition covering tropical and subtropical oceans. The potential factors affecting their distribution patterns were assessed including the distance to coastal regions, oceanic subtropical gyres, currents and biogeochemical processes. Field evidence of biogeochemical controls on the occurrence of PFASs was tentatively assessed considering environmental variables (solar radiation, temperature, chlorophyll a concentrations among others), and these showed significant correlations with some PFASs, but explaining small to moderate percentages of variability

  6. Brain region distribution and patterns of bioaccumulative perfluoroalkyl carboxylates and sulfonates in east greenland polar bears (Ursus maritimus).

    Science.gov (United States)

    Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune

    2013-03-01

    The present study investigated the comparative accumulation of perfluoroalkyl acids (PFAAs) in eight brain regions of polar bears (Ursus maritimus, n = 19) collected in 2006 from Scoresby Sound, East Greenland. The PFAAs studied were perfluoroalkyl carboxylates (PFCAs, C(6) -C(15) chain lengths) and sulfonates (C(4) , C(6) , C(8) , and C(10) chain lengths) as well as selected precursors including perfluorooctane sulfonamide. On a wet-weight basis, blood-brain barrier transport of PFAAs occurred for all brain regions, although inner regions of the brain closer to incoming blood flow (pons/medulla, thalamus, and hypothalamus) contained consistently higher PFAA concentrations compared to outer brain regions (cerebellum, striatum, and frontal, occipital, and temporal cortices). For pons/medulla, thalamus, and hypothalamus, the most concentrated PFAAs were perfluorooctane sulfonate (PFOS), ranging from 47 to 58 ng/g wet weight, and perfluorotridecanoic acid, ranging from 43 to 49 ng/g wet weight. However, PFOS and the longer-chain PFCAs (C(10) -C(15) ) were significantly (p  0.05) different among brain regions. The burden of the sum of PFCAs, perfluoroalkyl sulfonates, and perfluorooctane sulfonamide in the brain (average mass, 392 g) was estimated to be 46 µg. The present study demonstrates that both PFCAs and perfluoroalkyl sulfonates cross the blood-brain barrier in polar bears and that wet-weight concentrations are brain region-specific. Copyright © 2012 SETAC.

  7. [Tetracyclines, sulfonamides and metronidazole].

    Science.gov (United States)

    Pérez-Trallero, Emilio; Iglesias, Luis

    2003-11-01

    Tetracyclines form a group of natural and semisynthetic products that acts inhibiting the bacterial protein synthesis. They are bacteriostatic agents, exhibiting activity against a wide range of organisms, but they are at the present of limited use because of their acquired resistance. Doxycycline is currently the most frequently used tetracycline in human medicine and it is included in the List of Essential Medicines of the World Health Organization. Sulfonamides are synthetic, broad-spectrum bacteriostatic antibiotics. They were the first effective systemic antimicrobial agents. Their mode of action is based on the inhibition of DNA synthesis. Due to their toxicity and high adquired resistance their use is currently very low. Metronidazole is the main compound of 5-nitroimidazole family. It is a very active bactericidal antibiotic against anaerobic and some microaerophilic bacteria and it is still very useful in the treatment of bacterian and parasitic infections.

  8. Quinoline-2-sulfonamide

    Directory of Open Access Journals (Sweden)

    Joachim Kusz

    2013-08-01

    Full Text Available In the title compound, C9H8N2O2S, the sulfamoyl –NH2 group is involved in intermolecular hydrogen bonding with the sulfonamide O and quinoline N atoms. In the crystal, molecules are linked into dimers via pairs of N—H...N hydrogen bonds, forming an R22(10 motif. The dimers are further assembled into chains parallel to the b axis through N—H...O hydrogen bonds, generating a C(4 motif. The crystal packing is additionally stabilized by intermolecular C—H...O interactions. The crystal studied was a non-merohedral twin with a domain ratio of 0.938 (2:0.062 (2. Density functional theory (DFT calculations, at the B3LYP/6–31 G(d,p level of theory, were used to optimize the molecular structure and to determine interaction energies for the title compound. The resulting interaction energy is ∼4.4 kcal mol−1 per bridge for the C(4 chain and ∼5.9 kcal mol−1 per bridge for the R22(10 motif.

  9. Airborne Precursors Predict Maternal Serum Perfluoroalkyl Acid Concentrations.

    Science.gov (United States)

    Makey, Colleen M; Webster, Thomas F; Martin, Jonathan W; Shoeib, Mahiba; Harner, Tom; Dix-Cooper, Linda; Webster, Glenys M

    2017-07-05

    Human exposure to persistent perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctanesulfonate (PFOS), can occur directly from contaminated food, water, air, and dust. However, precursors to PFAAs (PreFAAs), such as dipolyfluoroalkyl phosphates (diPAPs), fluorotelomer alcohols (FTOHs), perfluorooctyl sulfonamides (FOSAs), and sulfonamidoethanols (FOSEs), which can be biotransformed to PFAAs, may also be a source of exposure. PFAAs were analyzed in 50 maternal sera samples collected in 2007-2008 from participants in Vancouver, Canada, while PFAAs and PreFAAs were measured in matching samples of residential bedroom air collected by passive sampler and in sieved vacuum dust (<150 μm). Concentrations of PreFAAs were higher than for PFAAs in air and dust. Positive associations were discovered between airborne 10:2 FTOH and serum PFOA and PFNA and between airborne MeFOSE and serum PFOS. On average, serum PFOS concentrations were 2.3 ng/mL (95%CI: 0.40, 4.3) higher in participants with airborne MeFOSE concentrations in the highest tertile relative to the lowest tertile. Among all PFAAs, only PFNA in air and vacuum dust predicted serum PFNA. Results suggest that airborne PFAA precursors were a source of PFOA, PFNA, and PFOS exposure in this population.

  10. Synthesis and characterization of novel sulfonamides derivatives

    African Journals Online (AJOL)

    3Department of Chemistry, Comsat Institute of Information & Technology Riawind road. Lahore ... Newer sulfonamides and their derivatives has obtained great attention in pharmaceutical field in ... MS data was recorded on Finnigan MAT 112 mass ..... potent and orally active sulfonamide ETB selective antagonists. Bioorg.

  11. Characterization of occurrence, sources and sinks of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in a tropical urban catchment

    International Nuclear Information System (INIS)

    Chen, Huiting; Reinhard, Martin; Nguyen, Tung Viet; You, Luhua; He, Yiliang; Gin, Karina Yew-Hoong

    2017-01-01

    Understanding the sources, occurrence and sinks of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the urban water cycle is important to protect and utilize local water resources. Concentrations of 22 target PFASs and general water quality parameters were determined monthly for a year in filtered water samples from five tributaries and three sampling stations of an urban water body. Of the 22 target PFASs, 17 PFASs were detected with a frequency >93% including PFCAs: C4-C12 perfluoroalkyl carboxylates, C4, C6, C8, and C10 perfluoroalkane sulfonates, perfluorooctane sulfonamides and perfluorooctane sulfonamide substances (FOSAMs), C10 perfluoroalkyl phosphonic acid (C10 PFPA), 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and C8/C8 perfluoroalkyl phosphinic acid (C8/C8-PFPIA). The most abundant PFASs in water were PFBS (1.4–55 ng/L), PFBA (1.0–23 ng/L), PFOS (1.5–24 ng/L) and PFOA (2.0–21 ng/L). In the tributaries, PFNA concentrations ranged from 1.2 to 87.1 ng/L except in the May 2013 samples of two tributaries, which reached 520 and 260 ng/L. Total PFAS concentrations in the sediment samples ranged from 1.6 to 15 ng/g d.w. with EtFOSAA, PFDoA, PFOS and PFDA being the dominant species. Based on water and sediment data, two types of sources were inferred: one-time or intermittent point sources and continuous non-point sources. FOSAMs and PFOS released continually from non-point sources, C8/C8 PFPIA, PFDoA and PFUnA was released from point sources. The highly water soluble short-chain PFASs including PFBA, PFPeA and PFBS remained predominantly in the water column. The factors governing solution phase concentrations appear to be compound hydrophobicity and sorption to suspended particles. Correlation of the dissolved phase concentrations with precipitation data suggested stormwater was a significant source of PFBA, PFBS, PFUnA and PFDoA. Negative correlations with precipitation indicated sources feeding FOSAA and FOSA directly into the tributaries

  12. Indoor and outdoor poly- and perfluoroalkyl substances (PFASs) in Korea determined by passive air sampler

    International Nuclear Information System (INIS)

    Kim, Seung-Kyu; Shoeib, Mahiba; Kim, Kyeong-Soo; Park, Jong-Eun

    2012-01-01

    Despite concerns to their increasing contribution to ecological and human exposure, the atmospheric levels of poly- and perfluoroalkyl substances (PFASs) have been determined mainly in Europe and North America. This study presents the indoor and outdoor air concentrations of volatile PFASs [fluorotelomer alcohols (FTOHs), and perfluoroalkyl sulfonamides/sulfonamidoethanols/sulfonamide ethyl acetate (FOSAs/FOSEs/FOSEA)] for the first time in Korean cities. In contrast to the good agreement observed for indoor FTOHs levels in Korea and Europea/North America, FOSAs/FOSEs levels were 10–100-fold lower in Korean indoor air, representing a cultural difference of indoor source. Korean outdoor air contained higher PFAS levels than indoor air, and additionally showed different PFAS composition profile from indoor air. Thus, indoor air would not likely be a main contributor to atmospheric PFAS contamination in Korea, in contrast to western countries. Inhalation exposure of volatile PFASs was estimated to be a minor contributor to PFOA and PFOS exposure in Korea. - Highlights: ► Volatile PFASs were measured in indoor and outdoor airs of Korea, for the first time. ► Cultural difference in indoor source was observed for Korea v.s. western countries. ► Furthermore, PFASs concentrations were higher in indoor air than outdoor air. ► Indoor air was not a major contributor to atmospheric PFASs contamination in Korea. ► Release from industrial activities was considered a possible source. - Korean outdoor air showed not only different PFAS composition profile but higher PFAS levels than indoor airs, indicating indoor air would not be a main source to Korean atmospheric PFASs.

  13. Tissue-specific concentrations and patterns of perfluoroalkyl carboxylates and sulfonates in East Greenland polar bears.

    Science.gov (United States)

    Greaves, Alana K; Letcher, Robert J; Sonne, Christian; Dietz, Rune; Born, Erik W

    2012-11-06

    Several perfluoroalkyl carboxylates (PFCAs) and perfluoroalkyl sulfonates (PFSAs) of varying chain length are bioaccumulative in biota. However, wildlife reports have focused on liver and with very little examination of other tissues, and thus there is a limited understanding of their distribution and potential effects in the mammalian body. In the present study, the comparative accumulation of C(6) to C(15) PFCAs, C(4), C(6), C(8) and C(10) PFSAs, and select precursors were examined in the liver, blood, muscle, adipose, and brain of 20 polar bears (Ursus maritimus) from Scoresby Sound, Central East Greenland. Overall, PFSA and PFCA concentrations were highest in liver followed by blood > brain > muscle ≈ adipose. Liver and blood samples contained proportionally more of the shorter/medium chain length (C(6) to C(11)) PFCAs, whereas adipose and brain samples were dominated by longer chain (C(13) to C(15)) PFCAs. PFCAs with lower lipophilicities accumulated more in the liver, whereas the brain accumulated PFCAs with higher lipophilicities. The concentration ratios (±SE) between perfluorooctane sulfonate and its precursor perfluorooctane sulfonamide varied among tissues from 9 (±1):1 (muscle) to 36 (±7):1 (liver). PFCA and PFSA patterns in polar bears indicate that the pharmacokinetics of these compounds are to some extent tissue-specific, and are the result of several factors that may include differing protein interactions throughout the body.

  14. Worldwide drinking water occurrence and levels of newly-identified perfluoroalkyl and polyfluoroalkyl substances.

    Science.gov (United States)

    Kaboré, Hermann A; Vo Duy, Sung; Munoz, Gabriel; Méité, Ladji; Desrosiers, Mélanie; Liu, Jinxia; Sory, Traoré Karim; Sauvé, Sébastien

    2018-03-01

    In the last decade or so, concerns have arisen with respect to the widespread occurrence of perfluoroalkyl acids (PFAAs) in the environment, food, drinking water, and humans. In this study, the occurrence and levels of a large range of perfluoroalkyl and polyfluoroalkyl substances (PFASs) were investigated in drinking water (bottled and tap water samples) from various locations around the world. Automated off-line solid phase extraction followed by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry was used to analyze PFASs of various chain lengths and functional groups. In total, 29 target and 104 suspect-target PFASs were screened in drinking water samples (n=97) from Canada and other countries (Burkina Faso, Chile, Ivory Coast, France, Japan, Mexico, Norway, and the USA) in 2015-2016. Out of the 29 PFASs quantitatively analyzed, perfluorocarboxylates (PFCAs: C 4/14 ), perfluoroalkane sulfonates (PFSAs: C 4 , C 6 , C 8 ), and perfluoroalkyl acid precursors (e.g., 5:3 fluorotelomer carboxylate (5:3 FTCA)) were recurrently detected in drinking water samples (concentration range: water samples from Canada showed noteworthy differences depending on their source; for instance, ∑ 29 PFASwas significantly greater in those produced from the Great Lakes/St. Lawrence River ecosystem than those produced from other types of sources (14 versus 5.3ngL -1 , respectively). A suspect-target screening approach indicated that other perfluoroalkane sulfonamides (FBSA, FHxSA), perfluoroethyl cyclohexane sulfonate (PFECHS), ultrashort chain (C 2 -C 3 ) PFSAs (PFEtS, PFPrS), and two additional PFSAs (PFPeS (C 5 ) and PFHpS (C 7 )) were repeatedly present in tap water samples (concentration ranges: water. According to the newly updated US EPA health advisory for PFOS and PFOA (70ngL -1 ), the drinking water samples collected in the present monitoring would not pose a health risk to consumers as regards PFAA levels. Copyright © 2017 Elsevier B

  15. Characterization of occurrence, sources and sinks of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in a tropical urban catchment.

    Science.gov (United States)

    Chen, Huiting; Reinhard, Martin; Nguyen, Tung Viet; You, Luhua; He, Yiliang; Gin, Karina Yew-Hoong

    2017-08-01

    Understanding the sources, occurrence and sinks of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in the urban water cycle is important to protect and utilize local water resources. Concentrations of 22 target PFASs and general water quality parameters were determined monthly for a year in filtered water samples from five tributaries and three sampling stations of an urban water body. Of the 22 target PFASs, 17 PFASs were detected with a frequency >93% including PFCAs: C4-C12 perfluoroalkyl carboxylates, C4, C6, C8, and C10 perfluoroalkane sulfonates, perfluorooctane sulfonamides and perfluorooctane sulfonamide substances (FOSAMs), C10 perfluoroalkyl phosphonic acid (C10 PFPA), 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and C8/C8 perfluoroalkyl phosphinic acid (C8/C8-PFPIA). The most abundant PFASs in water were PFBS (1.4-55 ng/L), PFBA (1.0-23 ng/L), PFOS (1.5-24 ng/L) and PFOA (2.0-21 ng/L). In the tributaries, PFNA concentrations ranged from 1.2 to 87.1 ng/L except in the May 2013 samples of two tributaries, which reached 520 and 260 ng/L. Total PFAS concentrations in the sediment samples ranged from 1.6 to 15 ng/g d.w. with EtFOSAA, PFDoA, PFOS and PFDA being the dominant species. Based on water and sediment data, two types of sources were inferred: one-time or intermittent point sources and continuous non-point sources. FOSAMs and PFOS released continually from non-point sources, C8/C8 PFPIA, PFDoA and PFUnA was released from point sources. The highly water soluble short-chain PFASs including PFBA, PFPeA and PFBS remained predominantly in the water column. The factors governing solution phase concentrations appear to be compound hydrophobicity and sorption to suspended particles. Correlation of the dissolved phase concentrations with precipitation data suggested stormwater was a significant source of PFBA, PFBS, PFUnA and PFDoA. Negative correlations with precipitation indicated sources feeding FOSAA and FOSA directly into the tributaries

  16. Why sulfonamides are contraindicated in Rocky Mountain spotted fever

    OpenAIRE

    Ren, Vicky; Hsu, Sylvia

    2014-01-01

    Sulfonamide antibiotics are not effective for the treatment of Rocky Mountain spotted fever (RMSF). Patients suspected of having RMSF based on history and physical exam should be treated with doxycycline and not a sulfonamide to avoid increased morbidity and mortality.

  17. Why sulfonamides are contraindicated in Rocky Mountain spotted fever.

    Science.gov (United States)

    Ren, Vicky; Hsu, Sylvia

    2014-02-18

    Sulfonamide antibiotics are not effective for the treatment of Rocky Mountain spotted fever (RMSF). Patients suspected of having RMSF based on history and physical exam should be treated with doxycycline and not a sulfonamide to avoid increased morbidity and mortality.

  18. Hydroxylamine as an oxygen nucleophile: substitution of sulfonamide by a hydroxyl group in benzothiazole-2-sulfonamides

    NARCIS (Netherlands)

    Kamps, J.A.G.; Belle, R.; Mecinovic, J.

    2013-01-01

    Benzothiazole-2-sulfonamides react with an excess of hydroxylamine in aqueous solutions to form 2-hydroxybenzothiazole, sulfur dioxide, and the corresponding amine. Mechanistic studies that employ a combination of structure-reactivity relationships, oxygen labeling experiments, and (in)direct

  19. Generic Advantages

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Generic Advantages. Scalability an incremental coverage. Standardization. Business Plan Flexibility. Lifecycle Flexibility. Reliability. Service Interoperability. Changed Industry dynamics.

  20. Perfluoroalkyl substances and fish consumption.

    Science.gov (United States)

    Christensen, Krista Y; Raymond, Michelle; Blackowicz, Michael; Liu, Yangyang; Thompson, Brooke A; Anderson, Henry A; Turyk, Mary

    2017-04-01

    Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and dyslipidemia. The major source of PFAS exposure in the general population is thought to be consumption of seafood. In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported fish and shellfish consumption, using a representative sample of the U.S. Data on PFAS levels and self-reported fish consumption over the past 30 days were collected from the 2007-2008, 2009-2010, 2011-2012, and 2013-2014 cycles of the National Health and Nutrition Examination Survey. Twelve different PFAS were measured in serum samples from participants. Ordinary least squares regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with serum PFAS concentrations. Additional models were further adjusted for other potential exposures including military service and consumption of ready-to-eat and fast foods. Seven PFAS were detected in at least 30% of participants and were examined in subsequent analyses (PFDA, PFOA, PFOS, PFHxS, MPAH, PFNA, PFUA). The PFAS with the highest concentrations were PFOS, followed by PFOA, PFHxS and PFNA (medians of 8.3, 2.7, 1.5 and 1.0ng/mL). Fish consumption was generally low, with a median of 1.2 fish meals and 0.14 shellfish meals, reported over the past 30 days. After adjusting for demographic characteristics, total fish consumption was associated with reduced MPAH, and with elevated PFDE, PFNA and PFuDA. Shellfish consumption was associated with elevations of all PFAS examined except MPAH. Certain specific fish and shellfish types were also associated with specific PFAS. Adjustment for additional exposure variables resulted in little to no change in effect estimates for seafood variables. PFAS are emerging

  1. Perfluoroalkylation of Aryl-N,N-dimethyl Hydrazones Using Hypervalent Iodine(III) Reagents or Perfluoroalkyl Iodides.

    Science.gov (United States)

    Janhsen, Benjamin; Studer, Armido

    2017-11-17

    Radical trifluoromethylation of aryl N,N-dimethyl hydrazones using TBAI as an initiator and Togni's reagent as a trifluoromethyl radical source is described. Cascades proceed via electron-catalysis; this approach is generally more applicable to hydrazone perfluoroalkylation using perfluoroalkyl iodides as the radical precursors in combination with a base under visible-light initiation.

  2. 78 FR 62443 - Perfluoroalkyl Sulfonates and Long-Chain Perfluoroalkyl Carboxylate Chemical Substances; Final...

    Science.gov (United States)

    2013-10-22

    ...) for perfluoroalkyl sulfonate (PFAS) chemical substances to add PFAS chemical substances that have... designating (for all listed PFAS chemical substances) processing as a significant new use. EPA is also... 40 CFR 721.9582 for PFAS chemical substances to add PFAS chemical substances that have completed the...

  3. 77 FR 48924 - Perfluoroalkyl Sulfonates and Long-Chain Perfluoroalkyl Carboxylate Chemical Substances; Proposed...

    Science.gov (United States)

    2012-08-15

    ... perfluoroalkyl sulfonate (PFAS) chemical substances to add PFAS chemical substances that have completed the TSCA... listed PFAS chemical substances) processing as a significant new use. EPA is also proposing a SNUR for... is proposing to amend a SNUR at Sec. 721.9582 for PFAS chemical substances to add PFAS chemical...

  4. Family Genericity

    DEFF Research Database (Denmark)

    Ernst, Erik

    2006-01-01

    Type abstraction in object-oriented languages embody two techniques, each with its own strenghts and weaknesses. The first technique is extension, yielding abstraction mechanisms with good support for gradual specification. The prime example is inheritance. The second technique is functional abst...... the result as family genericity. The presented language design has been implemented....

  5. Do perfluoroalkyl compounds impair human semen quality?

    DEFF Research Database (Denmark)

    Joensen, Ulla Nordström; Bossi, Rossana; Leffers, Henrik

    2009-01-01

    BACKGROUND: Perfluoroalkyl acids (PFAAs) are found globally in wildlife and humans and are suspected to act as endocrine disruptors. There are no previous reports of PFAA levels in adult men from Denmark or of a possible association between semen quality and PFAA exposure. OBJECTIVES: We investig......BACKGROUND: Perfluoroalkyl acids (PFAAs) are found globally in wildlife and humans and are suspected to act as endocrine disruptors. There are no previous reports of PFAA levels in adult men from Denmark or of a possible association between semen quality and PFAA exposure. OBJECTIVES: We...... investigated possible associations between PFAAs and testicular function. We hypothesized that higher PFAA levels would be associated with lower semen quality and lower testosterone levels. METHODS: We analyzed serum samples for levels of 10 different PFAAs and reproductive hormones and assessed semen quality......-gonadal hormones among men with high PFOS-PFOA levels. CONCLUSION: High PFAA levels were associated with fewer normal sperm. Thus, high levels of PFAAs may contribute to the otherwise unexplained low semen quality often seen in young men. However, our findings need to be corroborated in larger studies....

  6. Long-term effects of prenatal exposure to perfluoroalkyl substances on female reproduction

    DEFF Research Database (Denmark)

    Kristensen, Susanne Lund; Ramlau-Hansen, Cecilia; Ernst, Erik

    2013-01-01

    Does prenatal exposure to perfluoroalkyl substances (PFASs) have long-term effects on female reproductive function?.......Does prenatal exposure to perfluoroalkyl substances (PFASs) have long-term effects on female reproductive function?....

  7. Relationship between peroxisome proliferator-activated receptor alpha activity and cellular concentration of 14 perfluoroalkyl substances in HepG2 cells.

    Science.gov (United States)

    Rosenmai, Anna Kjerstine; Ahrens, Lutz; le Godec, Théo; Lundqvist, Johan; Oskarsson, Agneta

    2018-02-01

    Peroxisome proliferator-activated receptor alpha (PPARα) is a molecular target for perfluoroalkyl substances (PFASs). Little is known about the cellular uptake of PFASs and how it affects the PPARα activity. We investigated the relationship between PPARα activity and cellular concentration in HepG2 cells of 14 PFASs, including perfluoroalkyl carboxylates (PFCAs), perfluoroalkyl sulfonates and perfluorooctane sulfonamide (FOSA). Cellular concentrations were determined by high-performance liquid chromatography-tandem mass spectrometry and PPARα activity was determined in transiently transfected cells by reporter gene assay. Cellular uptake of the PFASs was low (0.04-4.1%) with absolute cellular concentrations in the range 4-2500 ng mg -1 protein. Cellular concentration of PFCAs increased with perfluorocarbon chain length up to perfluorododecanoate. PPARα activity of PFCAs increased with chain length up to perfluorooctanoate. The maximum induction of PPARα activity was similar for short-chain (perfluorobutanoate and perfluoropentanoate) and long-chain PFCAs (perfluorododecanoate and perfluorotetradecanoate) (approximately twofold). However, PPARα activities were induced at lower cellular concentrations for the short-chain homologs compared to the long-chain homologs. Perfluorohexanoate, perfluoroheptanoate, perfluorooctanoate, perfluorononanoate (PFNA) and perfluorodecanoate induced PPARα activities >2.5-fold compared to controls. The concentration-response relationships were positive for all the tested compounds, except perfluorooctane sulfonate PFOS and FOSA, and were compound-specific, as demonstrated by differences in the estimated slopes. The relationships were steeper for PFCAs with chain lengths up to and including PFNA than for the other studied PFASs. To our knowledge, this is the first report establishing relationships between PPARα activity and cellular concentration of a broad range of PFASs. Copyright © 2017 John Wiley & Sons, Ltd.

  8. Effect of humic acid (HA) on sulfonamide sorption by biochars

    International Nuclear Information System (INIS)

    Lian, Fei; Sun, Binbin; Chen, Xi; Zhu, Lingyan; Liu, Zhongqi; Xing, Baoshan

    2015-01-01

    Effect of quantity and fractionation of loaded humic acid (HA) on biochar sorption for sulfonamides was investigated. The HA was applied in two different modes, i.e. pre-coating and co-introduction with sorbate. In pre-coating mode, the polar fractions of HA tended to interact with low-temperature biochars via H-bonding, while the hydrophobic fractions were likely to be adsorbed by high-temperature biochars through hydrophobic and π-π interactions, leading to different composition and structure of the HA adlayers. The influences of HA fractionation on biochar sorption for sulfonamides varied significantly, depending on the nature of interaction between HA fraction and sorbate. Meanwhile, co-introduction of HA with sulfonamides revealed that the effect of HA on sulfonamide sorption was also dependent on HA concentration. These findings suggest that the amount and fractionation of adsorbed HA are tailored by the surface properties of underlying biochars, which differently affect the sorption for organic contaminants. - Highlights: • Effect of quantity and fractionation of coated HA on sorption of sulfonamides by BC was studied. • Fractionation of coated HA is tailored by surface properties of BC. • Roles of HA in BC sorption depend on interaction between HA adlayer and sorbate. • Roles of HA in sulfonamide sorption by BC also depend on HA aqueous concentration. - The quantity and fractionation of adsorbed HA play a major role in sulfonamide sorption by biochars

  9. Transport of sulfonamide antibiotics in crop fields during monsoon season.

    Science.gov (United States)

    Park, Jong Yol; Ruidisch, Marianne; Huwe, Bernd

    2016-11-01

    Previous studies have documented the occurrence of veterinary sulfonamide antibiotics in groundwater and rivers located far from pollution sources, although their transport and fate is relatively unknown. In mountainous agricultural fields, the transport behaviour can be influenced by climate, slope and physico-chemical properties of the sulfonamides. The objective of this research is to describe the transport behaviour of three sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) in sloped agricultural fields located in the Haean catchment, South Korea. During dry and monsoon seasons, a solute transport experiment was conducted in two typical sandy loam agricultural fields after application of antibiotics and potassium bromide as conservative tracers. Field measurement and modelling revealed that frequency and amount of runoff generation indicate a relation between slope and rain intensity during monsoon season. Since the steepness of slope influenced partitioning of precipitation between runoff and subsurface flow, higher loss of sulfonamide antibiotics and bromide by runoff was observed at the steeper sloped field. Bromide on topsoil rapidly infiltrated at high infiltration rates. On the contrary, the sulfonamides were relatively retarded in the upper soil layer due to adsorption onto soil particles. Presence of furrows and ridges affected the distribution of sulfonamide antibiotics in the subsurface due to gradient from wetter furrows to drier ridges induced by topography. Modelling results with HydroGeoSphere matched with background studies that describe physico-chemical properties of the sulfonamides interaction between soil and the antibiotic group, solute transport through vadose zone and runoff generation by storm events.

  10. Iatrogenic, sulfonamide-induced hypothyroid crisis in a Labrador Retriever.

    Science.gov (United States)

    Brenner, K; Harkin, K; Schermerhorn, T

    2009-12-01

    This case report describes a sulfonamide-induced hypothyroid crisis in a 4-year-old Labrador Retriever bitch. Empirical therapy with high-dose trimethoprim-sulfamethoxazole for 10 days produced signs of weakness, ataxia and mental depression and the clinicopathological results supported hypothyroid-induced central nervous system depression. Short-term levothyroxine sodium therapy led to complete resolution of all clinical signs and follow-up thyroid hormone assays ruled out underlying thyroid pathology. This case report is the first to highlight this potentially life-threatening manifestation of sulfonamide-induced hypothyroidism. Sulfonamide combinations are widely used antimicrobials in veterinary medicine and early recognition of this syndrome is critical.

  11. Removal efficiency of multiple poly- and perfluoroalkyl substances (PFASs) in drinking water using granular activated carbon (GAC) and anion exchange (AE) column tests.

    Science.gov (United States)

    McCleaf, Philip; Englund, Sophie; Östlund, Anna; Lindegren, Klara; Wiberg, Karin; Ahrens, Lutz

    2017-09-01

    Poly- and perfluoroalkyl substances (PFASs) have been detected in drinking water at relatively high concentrations throughout the world which has led to implementation of regulatory guidelines for specific PFASs in drinking water in several European countries and in the U.S. The Swedish National Food Agency has determined that the drinking water of over one third of the country's municipal consumers is at risk or already affected by PFAS contamination. The present study investigated the effects of perfluorocarbon chain length, functional group and isomer structure (branched or linear) on removal of multiple PFASs using granular activated carbon (GAC, Filtrasorb ® 400) and anion exchange (AE, Purolite ® A600) column experiments. The removal of 14 different PFASs, i.e. the C 3 C 11 , C 14 perfluoroalkyl carboxylic acids (PFCAs) (PFBA, PFPeA, PFHxA, PFHpA, PFOA, PFNA, PFDA, PFUnDA, PFDoDA, PFTeDA), perfluorooctane sulfonamide (FOSA), and the C 4 , C 6 , C 8 perfluoroalkyl sulfonic acids (PFSAs) (PFBS, PFHxS, PFOS), was monitored for a 217 day period. The results indicate the selective nature of PFAS removal as the absorbents are loaded with PFASs and dissolved organic carbon (DOC). A clear relationship between perfluorocarbon chain length and removal efficiency of PFASs using GAC and AE was found while PFASs with sulfonate functional groups displayed greater removal efficiency than those with carboxylate groups. Similarly, time to column breakthrough increased with increasing perfluorocarbon chain length and was greater for the PFSAs than the PFCAs for both GAC and AE. Shorter carbon chained PFASs such as PFBA, PFPeA, PFHxA showed desorption behavior and long-chained PFASs showed increased removal towards the end of the experiment indicating agglomeration or micelle development. Linear isomers of PFOS, PFHxS, and perfluorooctane sulfonamide (FOSA) had greater column removal efficiencies using GAC (and also for AE at greater bed volume throughput) than the branched

  12. Development and validation of a method for the quantification of extractable perfluoroalkyl acids (PFAAs) and perfluorooctane sulfonamide (FOSA) in textiles

    NARCIS (Netherlands)

    van der Veen, I.; Weiss, J.M.; Hanning, A.C.; de Boer, J.; Leonards, P.E.G.

    2016-01-01

    In textiles, like outdoor clothing, per- and polyfluoroalkyl substances (PFASs) are often used for durable water repellency (DWR) of the final products. The analytical performance to determine the concentration of these chemicals available for exposure to humans and to the environment need to be

  13. Methylenation of perfluoroalkyl ketones using a Peterson olefination approach.

    Science.gov (United States)

    Hamlin, Trevor A; Kelly, Christopher B; Cywar, Robin M; Leadbeater, Nicholas E

    2014-02-07

    An operationally simple, inexpensive, and rapid route for the olefination of a wide array of trifluoromethyl ketones to yield 3,3,3-trifluoromethylpropenes is reported. Using a Peterson olefination approach, the reaction gives good to excellent yields of the alkene products and can be performed without purification of the β-hydroxysilyl intermediate. The reaction can be extended to other perfluoroalkyl substituents and is easily scaled up. The alkenes prepared can be readily transformed into a variety of other perfluoroalkyl-containing compounds.

  14. Perfluoroalkyl acid distribution in various plant compartments ...

    Science.gov (United States)

    Crop uptake of perfluoroalkyl acids (PFAAs) from biosolids-amended soil has been identified as a potential pathway for PFAA entry into the terrestrial food chain. This study compared the uptake of PFAAs in greenhouse-grown radish (Raphanus sativus), celery (Apium graveolens var.dulce), tomato (Lycopersicon lycopersicum), and sugar snap pea (Pisum sativum var. macrocarpon) from an industrially impacted biosolids-amended soil, a municipal biosolids­ amended soil, and a control soil. Individual concentrations of PFAAs, on a dry weight basis, in mature, edible portions of crops grown in soil amended with PFAA industrially impacted biosolids were highest for perfluorooctanoate (PFOA; 67 ng/g) in radish root, perfluorobutanoate (PFBA;232 ng/g) in celery shoot, and PFBA (150 ng/g) in pea fruit. Comparatively, PFAA concentrations in edible compartments of crops grown in the municipal biosolids-amended soil and in the control soil were less than 25 ng/g. Bioaccumulation factors (BAFs) were calculated for the root, shoot, and fruit compartments (as applicable) of all crops grown in the industrially impacted soil. BAFs were highest for PFBA in the shoots of all crops, as well as in the fruit compartment of pea. Root­ soil concentration factors (RCFs) for tomato and pea were independent of PFAA chain length, while radish and celery RCFs showed a slight decrease with increasing chain length. Shoot-soil concentration factors (SCFs) for all crops showed a decrease with incre

  15. Legacy and Emerging Perfluoroalkyl Substances Are ...

    Science.gov (United States)

    Long-chain per- and polyfluoroalkyl substances (PFASs) are being replaced by short-chain PFASs and fluorinated alternatives. For ten legacy PFASs and seven recently discovered perfluoroalkyl ether carboxylic acids (PFECAs), we report (1) their occurrence in the Cape Fear River (CFR) watershed, (2) their fate in water treatment processes, and (3) their adsorbability on powdered activated carbon (PAC). In the headwater region of the CFR basin, PFECAs were not detected in raw water of a drinking water treatment plant (DWTP), but concentrations of legacy PFASs were high. The U.S. Environmental Protection Agency’s lifetime health advisory level (70 ng/L) for perfluorooctanesulfonic acid and perfluorooctanoic acid (PFOA) was exceeded on 57 of 127 sampling days. In raw water of a DWTP downstream of a PFAS manufacturer, the mean concentration of perfluoro-2-propoxypropanoic acid (PFPrOPrA), a replacement for PFOA, was 631 ng/L (n = 37). Six other PFECAs were detected, with three exhibiting chromatographic peak areas up to 15 times that of PFPrOPrA. At this DWTP, PFECA removal by coagulation, ozonation, biofiltration, and disinfection was negligible. The adsorbability of PFASs on PAC increased with increasing chain length. Replacing one CF2 group with an ether oxygen decreased the affinity of PFASs for PAC, while replacing additional CF2 groups did not lead to further affinity changes. The USEPA’s recently completed Unregulated Contaminant Monitoring Rule 3 (UCMR3) p

  16. Environmental-Fate Patterns for Perfluoroalkylates and their Precursors

    Science.gov (United States)

    Two sites with elevated concentrations of perfluoroalkylates (PFAs) and fluorotelomer alcohols (FTOHs) were studied: 1) agricultural fields near Decatur, AL on which sewage sludge had been applied; and 2) the Conasauga River system near Dalton, GA where treated sewage effluent is...

  17. Antimalarial activity of compounds comprising a primary benzene sulfonamide fragment.

    Science.gov (United States)

    Andrews, Katherine T; Fisher, Gillian M; Sumanadasa, Subathdrage D M; Skinner-Adams, Tina; Moeker, Janina; Lopez, Marie; Poulsen, Sally-Ann

    2013-11-15

    Despite the urgent need for effective antimalarial drugs with novel modes of action no new chemical class of antimalarial drug has been approved for use since 1996. To address this, we have used a rational approach to investigate compounds comprising the primary benzene sulfonamide fragment as a potential new antimalarial chemotype. We report the in vitro activity against Plasmodium falciparum drug sensitive (3D7) and resistant (Dd2) parasites for a panel of fourteen primary benzene sulfonamide compounds. Our findings provide a platform to support the further evaluation of primary benzene sulfonamides as a new antimalarial chemotype, including the identification of the target of these compounds in the parasite. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Perfluoroalkyl substances and food allergies in adolescents.

    Science.gov (United States)

    Buser, Melanie C; Scinicariello, Franco

    2016-03-01

    Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are a class of organic compounds that are persistent in the environment due to their stable carbon-fluorine backbone, which is not susceptible to degradation. Research suggests these chemicals may exert an immunotoxic effect. The aim of this study is to investigate the associations between four PFASs - perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS) - with food sensitization and food allergies in adolescent participants (ages 12-19years) in the National Health and Nutrition Examination Survey (NHANES) 2005-2006 and 2007-2010, respectively. We performed multivariate logistic regression to analyze the association between individual PFASs with food sensitization (defined as having at least 1 food-specific IgE level≥0.35kU/L) in NHANES 2005-2006 and food allergies (self-reported) in NHANES 2007-2010. Serum PFOA, PFOS, and PFHxS were statistically significantly associated with higher odds to have self-reported food allergies in NHANES 2007-2010. When using IgE levels as a marker of food sensitization, we found that serum PFNA was inversely associated with food sensitization (NHANES 2005-2006). In conclusion, we found that serum levels of PFASs were associated with higher odds to have self-reported food allergies. Conversely, adolescents with higher serum PFNA were less likely to be sensitized to food allergens. These results, along with previous studies, warrant further investigation, such as well-designed longitudinal studies. Published by Elsevier Ltd.

  19. Sorption behaviour of perfluoroalkyl substances in soils.

    Science.gov (United States)

    Milinovic, Jelena; Lacorte, Silvia; Vidal, Miquel; Rigol, Anna

    2015-04-01

    The sorption behaviour of three perfluoroalkyl substances (PFASs), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorobutane sulfonic acid (PFBS), was studied in six soils with contrasting characteristics, especially in the organic carbon content. Sorption isotherms were obtained by equilibrating the soil samples with 0.01 mol L(-1) CaCl2 solutions spiked with increasing concentrations of the target PFAS. The sorption reversibility of PFASs was also tested for some of the samples. Liquid chromatography coupled to tandem mass spectrometry was used to quantify the target PFASs in the solutions. Both the Freundlich and linear models were appropriate to describe the sorption behaviour of PFASs in soils, and enabled us to derive solid-liquid distribution coefficients (Kd) for each compound in each soil. Kd values increased from 19 to 295 mL g(-1) for PFOS, from 2.2 to 38 mL g(-1) for PFOA and from 0.4 to 6.8 mL g(-1) for PFBS, and were positively correlated with the organic carbon content of the soil. KOC values obtained from the correlations were 710, 96 and 17 mL g(-1) for PFOS, PFOA and PFBS, respectively. Whereas Kd values decreased in the sequence PFOS>PFOA>PFBS, desorption yields were lower than 13% for PFOS, from 24 to 58% for PFOA, and from 32 to 60% for PFBS. This shows that the physicochemical characteristics of PFASs, basically their hydrophobicity, controlled their sorption behaviour in soils, with PFOS being the most irreversibly sorbed PFAS. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Perfluoroalkyl substances and beta cell deficient diabetes.

    Science.gov (United States)

    Conway, Baqiyyah; Innes, Karen E; Long, Dustin

    2016-08-01

    Perfluoroalkyl substances (PFAS) are synthetic hydrocarbons shown to preserve pancreatic islet cell viability and reduce islet cell hypoxia and apoptosis. We investigated the relationship of serum PFAS with diabetes, and whether this varied by diabetes type. 6,460 individuals with and 60,439 without diabetes from the C8 Health Project, were categorized into three groups: type 1 (n=820), type 2 (n=4,291), or uncategorized diabetes (n=1,349, missing data on diabetes type or diabetes based on blood sugar at study entry). Four PFAS were investigated: perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), and perfluorononaoic acid (PFNA). PFAS levels were significantly lower in those with diabetes, and lowest in those with type 1 diabetes. In age and sex adjusted analyses, ORs (CI) for type 1, type 2, and uncategorized diabetes compared to no diabetes were 0.59 (0.54-0.64), 0.74 (0.71-0.77), 0.84 (0.78-0.90), respectively for PFHxS; 0.69 (0.65-0.74), 0.87 (0.89-0.91), 0.92 (0.88-0.97), respectively for PFOA; 0.65 (0.61-0.70), 0.86 (0.82-0.90), 0.93 (0.86-1.03), respectively for PFOS; and 0.65 (0.57-0.74), 0.94 (0.88-1.00), 0.95 (0.85-1.06), respectively for PFNA. Further adjustment for eGFR and other covariates did not eliminate these inverse associations. PFAS levels were negatively associated with diabetes. This inverse relationship was strongest for type 1 diabetes, suggesting the relationship with serum PFAS may vary with the severity of islet cell deficiency. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Discovery of tertiary sulfonamides as potent liver X receptor antagonists.

    Science.gov (United States)

    Zuercher, William J; Buckholz, Richard G; Campobasso, Nino; Collins, Jon L; Galardi, Cristin M; Gampe, Robert T; Hyatt, Stephen M; Merrihew, Susan L; Moore, John T; Oplinger, Jeffrey A; Reid, Paul R; Spearing, Paul K; Stanley, Thomas B; Stewart, Eugene L; Willson, Timothy M

    2010-04-22

    Tertiary sulfonamides were identified in a HTS as dual liver X receptor (LXR, NR1H2, and NR1H3) ligands, and the binding affinity of the series was increased through iterative analogue synthesis. A ligand-bound cocrystal structure was determined which elucidated key interactions for high binding affinity. Further characterization of the tertiary sulfonamide series led to the identification of high affinity LXR antagonists. GSK2033 (17) is the first potent cell-active LXR antagonist described to date. 17 may be a useful chemical probe to explore the cell biology of this orphan nuclear receptor.

  2. Analytik, Vorkommen und Verhalten aromatischer Sulfonamide in der aquatischen Umwelt

    OpenAIRE

    Hartig, Claudia

    2000-01-01

    Subject of this PhD-thesis are the analysis and behaviour of aromatic sulfonamides as organic micropollutants in the aquatic environment. On the grounds of their widespread application, bacteriostatics as well as benzene- and toluenesulfonamides (BTS) are investigated. Analysis of the sulfonamides consists of solid-phase extraction (LiChrolut EN) and HPLC-MS/MS. Limits of detection vary from 0.1-20 ng/L. The MS/MS detection is carried out in SRM mode. Matrix effects of the investigated second...

  3. Concentrations and patterns of perfluoroalkyl and polyfluoroalkyl substances in a river and three drinking water treatment plants near and far from a major production source.

    Science.gov (United States)

    Boiteux, Virginie; Dauchy, Xavier; Bach, Cristina; Colin, Adeline; Hemard, Jessica; Sagres, Véronique; Rosin, Christophe; Munoz, Jean-François

    2017-04-01

    Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are emerging contaminants that have been detected in the environment, biota and humans. Drinking water is a route of exposure for populations using water contaminated by PFAS discharges. This research entailed measuring concentrations, mass flows and investigating the fate of dozens PFASs in a river receiving effluents from a fluorochemical manufacturing facility. To measure the total concentration of perfluoroalkyl carboxylic acid (PFCA) precursors, an oxidative conversion method was used. Several dozen samples were collected in the river (water and sediment), in drinking water resources and at different treatment steps on four sampling dates. One PFCA and three fluorotelomers (FTs) were detected up to 62km downstream from the manufacturing facility. 6:2 Fluorotelomer sulfonamide alkylbetaine (6:2 FTAB) was the predominant PFAS with a mass flow of 3830g/day 5.2km downstream from the facility. At all sampling points, PFAS concentrations in sediment were quite low (activated carbon filtration, ozonation or chlorination) did not efficiently remove PFASs. Furthermore, an increase in concentration of certain PFASs was observed after ozonation, suggesting that some FTs such as 6:2 FTAB can break down. Only nanofiltration was able to remove all the analyzed PFASs. In the treated water, total PFAS concentrations never exceeded 60ng/L. The oxidative conversion method revealed the presence of unidentified PFCA precursors in the river. Therefore, 18 to 77% of the total PFCA content after oxidation consisted of unidentified chemical species. In the treated water, these percentages ranged from 0 to 29%, relatively and reassuringly low values. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Bithiophene sulfonamide-based molecular and polymeric semiconductors

    Science.gov (United States)

    Facchetti, Antonio; Marks, Tobin J.; Xia, Yu; Drees, Martin; Melkonyan, Ferdinand; Zhao, Wei

    2017-05-30

    The present invention relates to new semiconducting compounds having at least one optionally substituted bithiophene sulfonamide moiety. The compounds disclosed herein can exhibit high carrier mobility and/or efficient light absorption/emission characteristics, and can possess certain processing advantages such as solution-processability and/or good stability at ambient conditions.

  5. Sorption of fluoroquinolones and sulfonamides in 13 Brazilian soils.

    Science.gov (United States)

    Leal, Rafael Marques Pereira; Alleoni, Luis Reynaldo Ferracciú; Tornisielo, Valdemar Luiz; Regitano, Jussara Borges

    2013-08-01

    Animal production is a leading economic activity in Brazil and antibiotics are widely used. However, the occurrence, behavior, and impacts of antibiotics in Brazilian soils are still poorly known. We evaluated the sorption behavior of four fluoroquinolones (norfloxacin, ciprofloxacin, danofloxacin, and enrofloxacin) and five sulfonamides (sulfadiazine, sulfachloropyridazine, sulfamethoxazole, sulfadimidine, and sulfathiazole) in 13 Brazilian soils with contrasting physical, chemical, and mineralogical properties. Fluoroquinolone sorption was very high (Kd≥544 L kg(-1)) whereas sulfonamide sorption ranged from low to high (Kd=0.7-70.1 L kg(-1)), consistent with previous reports in the literature. Soil texture and cation exchange capacity were the soil attributes that most affected sorption. Cation exchange was the most important sorption mechanism for the fluoroquinolones in highly weathered tropical soils, although cation bridging and ion pairing could not be ruled out. Hydrophobic partition played an important role in the sorption of the sulfonamides, but sorption was also affected by non-hydrophobic interactions with organic and/or mineral surfaces. Sorption for both compound classes tended to be higher in soils with high Al and Fe oxihydroxide contents, but they were not correlated with Kd values. No direct effect of soil pH was seen. The fluoroquinolones are not expected to leach even in worst-case scenarios (soils rich in sand and poor in organic carbon), whereas soil attributes dictate leaching potential for the sulfonamides. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Migration of perfluoroalkyl acids from food packaging to food simulants.

    Science.gov (United States)

    Xu, Y; Noonan, G O; Begley, T H

    2013-01-01

    A broad range of fluorochemicals is used to impart oil and water barrier properties to paper and paperboard food packaging. Many of the fluorochemicals are applied to paper and paperboard as complex mixtures containing reaction products and by-products and unreacted starting materials. This work primarily focussed on the determination of seven perfluorocarboxylic acids (PFCAs) in two commercially available food contact papers: a di-perfluoro-alkyloxy-amino-acid and a perfluoroalkyl phosphate surfactant. In addition, the migration of the PFCAs into five food simulants from two commercial packages was evaluated. All seven PFCAs were detected in the range of 700-2220 µg kg⁻¹ of paper, while three perfluoroalkyl sulphonates were under the LOD. Results from migration tests showed that migration depends on paper characteristics, time and food simulant. The percentage of migration after 10 days at 40°C ranged from 4.8% to 100% for the two papers and different food simulants.

  7. The generic article

    NARCIS (Netherlands)

    Farkas, D.F.; Swart, Henriëtte de

    2005-01-01

    We take a fresh look at the connection between genericity and (in)definiteness by reconsidering a long-standing puzzle concerning the relation between definiteness and genericity. We contrast English on the one hand and Romance languages and Hungarian on the other, focusing on generic sentences

  8. Feasibility of Biodegradation of Polyfluoroalkyl and Perfluoroalkyl Substances

    OpenAIRE

    Tseng, Nancy Shiao-lynn

    2012-01-01

    Polyfluoroalkyl and perfluoroalkyl substances (PFASs) are highly stable organic compounds, which contain multiple carbon-fluorine bonds. They are used in various commercial products, including aqueous fire-fighting foams (AFFF) and products with non-stick coatings. However, these compounds are reproductive and developmental toxicants, endocrine disrupters, and potential human carcinogens. They are found globally as emerging contaminants in groundwater and surface water resources. The two most...

  9. Perfluoroalkyl substance contamination of the Llobregat River ecosystem (Mediterranean area, NE Spain)

    International Nuclear Information System (INIS)

    Campo, Julian; Pérez, Francisca; Masiá, Ana; Picó, Yolanda; Farré, Marinella; Barceló, Damià

    2015-01-01

    The occurrence and sources of 21 perfluoroalkyl substances (PFASs: C4–C14, C16, C18 carboxylate, C4, C6–C8 and C10 sulfonates and C8 sulfonamide) were determined in water, sediment, and biota of the Llobregat River basin (NE Spain). Analytes were extracted by solid phase extraction (SPE) and determined by liquid chromatography triple quadrupole mass spectrometer (LC-QqQ-MS). All samples were contaminated with at least one PFAS, being the most frequently found perfluorobutanoate (PFBA), perfluorooctanoate (PFOA) and perfluorooctane sulfonate (L-PFOS). In general, mean PFAS concentrations measured in sediments (0.01–3.67 ng g −1 ) and biota (0.79–431 μg kg −1 ) samples were higher than those found in water (0.01–233 ng L −1 ). L-PFOS presented very high levels in biota and water, particularly in the Anoia River where a maximum concentration of 2.71 μg L −1 was related to important industrial activities. However, this pollution does not extend down the Llobregat River according to cumulated values. None of the hazard quotients (HQ) calculated indicate potential risk for the different tropic levels considered (algae, Daphnia sp. and fish). According to Maximum Allowable Concentration (MAC) proposed by the European Commission (L-PFOS) and to Provisional Health Advisory (PHA) values (PFOA, L-PFOS) established by the United States Environmental Protection Agency (US EPA), only two water samples exceeded PHA concentration for L-PFOS. - Highlights: • Distribution of 21 PFASs in water, sediment, biota of Llobregat River is investigated. • High L-PFOS concentration in the Anoia River related to industrial activities • PFAS concentration was sediment ≫ water, suggesting accumulation in river's mouth. • Highest PFAS values in biota observed after the Cardener River's confluence • Barbus graellsii accumulates more PFHxA and Cyprinus carpio more L-PFOS. • None of the calculated HQs indicates potential risk for the different tropic

  10. Distribution and fate of perfluoroalkyl substances in Mediterranean Spanish sewage treatment plants

    International Nuclear Information System (INIS)

    Campo, Julian; Masiá, Ana; Picó, Yolanda; Farré, Marinella; Barceló, Damià

    2014-01-01

    The concentrations of 21 perfluoroalkyl substances (PFASs: C4–C14, C16, C18 carboxylates, C4, C6–C8 and C10 sulfonates and C8 sulfonamide) were determined in influent, effluent and sludge from 16 different sewage treatment plants (STPs) located in the Ebro (6), Guadalquivir (5), Jucar (2) and Llobregat (3) Rivers, in two consecutive years (2010 and 2011). The analytes were extracted by solid phase extraction (SPE) and determined by Liquid Chromatography triple Quadrupole Mass Spectrometer (LC-QqQ-MS). All samples, except two sludges from Guadalquivir River STPs, were contaminated with at least one PFAS. Perfluorobutanoate (PFBA), perfluoropentanoate (PFPeA) and perfluorooctane sulfonate (L-PFOS) were the most frequently detected. The highest concentration in water was determined in 2010 in a Guadalquivir River STP (perfluorohexanoate, PFHxA: 5.60 μg L −1 ) and, in 2011, in an Ebro River STP (perfluorobutane sulfonate, L-PFBS: 0.31 μg L −1 ). In sludge samples, the maximum concentration in 2010 was 1.79 μg g −1 dry weight (dw) (L-PFOS, in a Llobregat River STP), and in 2011, 1.88 μg g −1 dw (PFBA, in one Guadalquivir River STP). High PFAS values in sludge could be related to positive removal efficiencies, and can be attributed to their adsorption. Distribution coefficients (Kd) were determined ranging between 0.32 L kg −1 (perfluorohexane sulfonate, L-PFHxS) and 36.6 10 3 L kg −1 (PFBA). The total PFAS loads discharged into the basins showed high values for the Ebro River STPs (66.9 g day −1 ) while in the others, the loads were between 3.97 g day −1 , in the Jucar STPs, and 32.2 g day −1 , in the Guadalquivir STPs. - Highlights: • Twenty-one PFASs were quantified in wastewater and dehydrated sludge samples. • PFAS loads discharged to the Rivers were from 16 g day −1 (Llobregat) to 67 g day −1 (Ebro). • STPs could be a focal point of PFAS contamination to the Rivers. • Removal efficiencies in STPs confirm that PFASs are only

  11. Association between thyroid profile and perfluoroalkyl acids: Data from NHNAES 2007–2008

    Energy Technology Data Exchange (ETDEWEB)

    Jain, Ram B., E-mail: Jain.ram.b@gmail.com

    2013-10-15

    The effect of six perfluoroalkyl acids (PFAAs), namely, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDE), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamide) acetic acid (MPAH), and perfluorononanoic acid (PFNA) on the levels of six thyroid function variables, namely, thyroid stimulating hormone (TSH), free and total thyroxine (FT4, TT4), free and total triiodothyronine (FT3, TT3), and thyroglobulin (TGN) was evaluated. Data from National Health and Nutrition Examination Survey for the years 2007–2008 were used for this evaluation. TSH levels increased with increase in levels of PFOA (p<0.01). There were no statistically significant associations between the levels of FT3, and FT4 with the levels of any of the six PFAAs. Levels of TT3 were found to increase with the levels of PFOA (p=0.01) and TT4 levels were found to increase with increase in PFHxS levels (p<0.01). Males had statistically significantly higher levels of FT3 than females and females had statistically significantly higher levels of TT4 than males. As compared to non-Hispanics whites and Hispanics, non-Hispanic blacks had lower levels of TSH, FT3, TT3, and TT4 but Hispanics had the lowest levels of TGN. Age was negatively associated with FT3 and TT3 but positively associated with FT4 and TT4. Non-smokers had higher levels of TSH and TT4 than smokers and smokers had higher levels of FT3 and TGN than non-smokers. Iodine deficiency was associated with increased levels of TSH, TT3, TT4, and TGN. -- Highlights: • Levels of total triiodothyronine were found to increase with the levels of PFOA. • Total thyroxine increased with increase in levels of perfluorohexane sulfonic acid. • There was a positive association between the levels of PFOA and TSH. • Iodine deficiency was associated with elevated levels of TSH, total T3 and T4. • Iodine deficiency was associated with elevated levels of thyroglobulin.

  12. Distribution and fate of perfluoroalkyl substances in Mediterranean Spanish sewage treatment plants

    Energy Technology Data Exchange (ETDEWEB)

    Campo, Julian, E-mail: Julian.Campo@uv.es [Food and Environmental Safety Research Group (SAMA-UV), Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n. 46100, Burjassot, València (Spain); Masiá, Ana; Picó, Yolanda [Food and Environmental Safety Research Group (SAMA-UV), Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n. 46100, Burjassot, València (Spain); Farré, Marinella [Department of Environmental Chemistry (IDAEA-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Barceló, Damià [Department of Environmental Chemistry (IDAEA-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Catalan Institute of Water Research, ICRA Catalan Institute for Water Research — ICRA, C/Emili Grahit, 101, Edifici H2O, Parc Científic i Tecnològic de la Universitat de Girona, E-17003 Girona (Spain)

    2014-02-01

    The concentrations of 21 perfluoroalkyl substances (PFASs: C4–C14, C16, C18 carboxylates, C4, C6–C8 and C10 sulfonates and C8 sulfonamide) were determined in influent, effluent and sludge from 16 different sewage treatment plants (STPs) located in the Ebro (6), Guadalquivir (5), Jucar (2) and Llobregat (3) Rivers, in two consecutive years (2010 and 2011). The analytes were extracted by solid phase extraction (SPE) and determined by Liquid Chromatography triple Quadrupole Mass Spectrometer (LC-QqQ-MS). All samples, except two sludges from Guadalquivir River STPs, were contaminated with at least one PFAS. Perfluorobutanoate (PFBA), perfluoropentanoate (PFPeA) and perfluorooctane sulfonate (L-PFOS) were the most frequently detected. The highest concentration in water was determined in 2010 in a Guadalquivir River STP (perfluorohexanoate, PFHxA: 5.60 μg L{sup −1}) and, in 2011, in an Ebro River STP (perfluorobutane sulfonate, L-PFBS: 0.31 μg L{sup −1}). In sludge samples, the maximum concentration in 2010 was 1.79 μg g{sup −1} dry weight (dw) (L-PFOS, in a Llobregat River STP), and in 2011, 1.88 μg g{sup −1} dw (PFBA, in one Guadalquivir River STP). High PFAS values in sludge could be related to positive removal efficiencies, and can be attributed to their adsorption. Distribution coefficients (Kd) were determined ranging between 0.32 L kg{sup −1} (perfluorohexane sulfonate, L-PFHxS) and 36.6 10{sup 3} L kg{sup −1} (PFBA). The total PFAS loads discharged into the basins showed high values for the Ebro River STPs (66.9 g day{sup −1}) while in the others, the loads were between 3.97 g day{sup −1}, in the Jucar STPs, and 32.2 g day{sup −1}, in the Guadalquivir STPs. - Highlights: • Twenty-one PFASs were quantified in wastewater and dehydrated sludge samples. • PFAS loads discharged to the Rivers were from 16 g day{sup −1} (Llobregat) to 67 g day{sup −1} (Ebro). • STPs could be a focal point of PFAS contamination to the Rivers.

  13. Association between thyroid profile and perfluoroalkyl acids: Data from NHNAES 2007–2008

    International Nuclear Information System (INIS)

    Jain, Ram B.

    2013-01-01

    The effect of six perfluoroalkyl acids (PFAAs), namely, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorodecanoic acid (PFDE), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamide) acetic acid (MPAH), and perfluorononanoic acid (PFNA) on the levels of six thyroid function variables, namely, thyroid stimulating hormone (TSH), free and total thyroxine (FT4, TT4), free and total triiodothyronine (FT3, TT3), and thyroglobulin (TGN) was evaluated. Data from National Health and Nutrition Examination Survey for the years 2007–2008 were used for this evaluation. TSH levels increased with increase in levels of PFOA (p<0.01). There were no statistically significant associations between the levels of FT3, and FT4 with the levels of any of the six PFAAs. Levels of TT3 were found to increase with the levels of PFOA (p=0.01) and TT4 levels were found to increase with increase in PFHxS levels (p<0.01). Males had statistically significantly higher levels of FT3 than females and females had statistically significantly higher levels of TT4 than males. As compared to non-Hispanics whites and Hispanics, non-Hispanic blacks had lower levels of TSH, FT3, TT3, and TT4 but Hispanics had the lowest levels of TGN. Age was negatively associated with FT3 and TT3 but positively associated with FT4 and TT4. Non-smokers had higher levels of TSH and TT4 than smokers and smokers had higher levels of FT3 and TGN than non-smokers. Iodine deficiency was associated with increased levels of TSH, TT3, TT4, and TGN. -- Highlights: • Levels of total triiodothyronine were found to increase with the levels of PFOA. • Total thyroxine increased with increase in levels of perfluorohexane sulfonic acid. • There was a positive association between the levels of PFOA and TSH. • Iodine deficiency was associated with elevated levels of TSH, total T3 and T4. • Iodine deficiency was associated with elevated levels of thyroglobulin

  14. Perfluoroalkyl substance contamination of the Llobregat River ecosystem (Mediterranean area, NE Spain)

    Energy Technology Data Exchange (ETDEWEB)

    Campo, Julian, E-mail: Julian.Campo@uv.es [Food and Environmental Safety Research Group (SAMA-UV), Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n. 46100, Burjassot, València (Spain); Pérez, Francisca [Department of Environmental Chemistry (IDAEA-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Masiá, Ana; Picó, Yolanda [Food and Environmental Safety Research Group (SAMA-UV), Faculty of Pharmacy, University of Valencia, Av. Vicent Andrés Estellés s/n. 46100, Burjassot, València (Spain); Farré, Marinella [Department of Environmental Chemistry (IDAEA-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Barceló, Damià [Department of Environmental Chemistry (IDAEA-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Catalan Institute for Water Research (ICRA), Emili Grahit, 101, Edifici H2O, Parc Científic i Tecnològic de la Universitat de Girona, E-17003 Girona (Spain)

    2015-01-15

    The occurrence and sources of 21 perfluoroalkyl substances (PFASs: C4–C14, C16, C18 carboxylate, C4, C6–C8 and C10 sulfonates and C8 sulfonamide) were determined in water, sediment, and biota of the Llobregat River basin (NE Spain). Analytes were extracted by solid phase extraction (SPE) and determined by liquid chromatography triple quadrupole mass spectrometer (LC-QqQ-MS). All samples were contaminated with at least one PFAS, being the most frequently found perfluorobutanoate (PFBA), perfluorooctanoate (PFOA) and perfluorooctane sulfonate (L-PFOS). In general, mean PFAS concentrations measured in sediments (0.01–3.67 ng g{sup −1}) and biota (0.79–431 μg kg{sup −1}) samples were higher than those found in water (0.01–233 ng L{sup −1}). L-PFOS presented very high levels in biota and water, particularly in the Anoia River where a maximum concentration of 2.71 μg L{sup −1} was related to important industrial activities. However, this pollution does not extend down the Llobregat River according to cumulated values. None of the hazard quotients (HQ) calculated indicate potential risk for the different tropic levels considered (algae, Daphnia sp. and fish). According to Maximum Allowable Concentration (MAC) proposed by the European Commission (L-PFOS) and to Provisional Health Advisory (PHA) values (PFOA, L-PFOS) established by the United States Environmental Protection Agency (US EPA), only two water samples exceeded PHA concentration for L-PFOS. - Highlights: • Distribution of 21 PFASs in water, sediment, biota of Llobregat River is investigated. • High L-PFOS concentration in the Anoia River related to industrial activities • PFAS concentration was sediment ≫ water, suggesting accumulation in river's mouth. • Highest PFAS values in biota observed after the Cardener River's confluence • Barbus graellsii accumulates more PFHxA and Cyprinus carpio more L-PFOS. • None of the calculated HQs indicates potential risk for the

  15. Gas chromatography-tandem mass spectrometry with atmospheric pressure chemical ionization for fluorotelomer alcohols and perfluorinated sulfonamides determination.

    Science.gov (United States)

    Portolés, Tania; Rosales, Luis E; Sancho, Juan V; Santos, F Javier; Moyano, Encarnación

    2015-09-25

    Ionization and in source-fragmentation behavior of four fluorotelomer alcohols (FTOH) (4:2 FTOH, 6:2 FTOH, 8:2 FTOH and 10:2 FTOH) and four N-alkyl fluorooctane sulfonamides/-ethanols (N-MeFOSA, N-EtFOSA, N-MeFOSE and N-EtFOSE) by APCI has been studied and compared with the traditionally used EI and CI. Protonated molecule was the base peak of the APCI spectrum in all cases giving the possibility of selecting it as a precursor ion for MS/MS experiments. Following, CID fragmentation showed common product ions for all FOSAs/FOSEs (C4F7 and C3F5). Nevertheless, the different functionality gave characteristic pattern fragmentations. For instance, FTOHs mainly loss H2O+HF, FOSAs showed the losses of SO2 and HF while FOSEs showed the losses of H2O and SO2. Linearity, repeatability and LODs have been studied obtaining instrumental LODs between 1 and 5fg. Finally, application to river water and influent and effluent waste water samples has been carried out in order to investigate the improvements in detection capabilities of this new source in comparison with the traditionally used EI/CI sources. Matrix effects in APCI have been evaluated in terms of signal enhancement/suppression when comparing standards in solvent and matrix. No matrix effects were observed and concentrations found in samples were in the range of 1-100pgL(-1) far below the LODs achieved with methods previously reported. Unknown related perfluoroalkyl substances, as methyl-sulfone and methyl-sulfoxide analogues for FTOHs, were also discovered and tentatively identified. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Sorption of perfluoroalkyl substances (PFASs) to an organic soil horizon - Effect of cation composition and pH.

    Science.gov (United States)

    Campos Pereira, Hugo; Ullberg, Malin; Kleja, Dan Berggren; Gustafsson, Jon Petter; Ahrens, Lutz

    2018-09-01

    Accurate prediction of the sorption of perfluoroalkyl substances (PFASs) in soils is essential for environmental risk assessment. We investigated the effect of solution pH and calculated soil organic matter (SOM) net charge on the sorption of 14 PFASs onto an organic soil as a function of pH and added concentrations of Al 3+ , Ca 2+ and Na + . Often, the organic C-normalized partitioning coefficients (K OC ) showed a negative relationship to both pH (Δlog K OC /ΔpH = -0.32 ± 0.11 log units) and the SOM bulk net negative charge (Δlog K OC  = -1.41 ± 0.40 per log unit mol c g -1 ). Moreover, perfluorosulfonic acids (PFSAs) sorbed more strongly than perfluorocarboxylic acids (PFCAs) and the PFAS sorption increased with increasing perfluorocarbon chain length with 0.60 and 0.83 log K OC units per CF 2 moiety for C 3 -C 10 PFCAs and C 4 , C 6 , and C 8 PFSAs, respectively. The effects of cation treatment and SOM bulk net charge were evident for many PFASs with low to moderate sorption (C 5 -C 8 PFCAs and C 6 PFSA). However for the most strongly sorbing and most long-chained PFASs (C 9 -C 11 and C 13 PFCAs, C 8 PFSA and perfluorooctane sulfonamide (FOSA)), smaller effects of cations were seen, and instead sorption was more strongly related to the pH value. This suggests that the most long-chained PFASs, similar to other hydrophobic organic compounds, are preferentially sorbed to the highly condensed domains of the humin fraction, while shorter-chained PFASs are bound to a larger extent to humic and fulvic acid, where cation effects are significant. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Circulating levels of perfluoroalkyl substances are associated with dietary patterns - A cross sectional study in elderly Swedish men and women.

    Science.gov (United States)

    Sjogren, Per; Montse, Rachel; Lampa, Erik; Salihovic, Samira; van Bavel, Bert; Lind, Lars; Lind, P Monica

    2016-10-01

    In our daily life, we are exposed to perfluoroalkyl substances (PFAS) with possible health implications. The main exposure route for these substances is diet but comparative studies on how dietary habits influence exposure are lacking. To examine the relations between blood levels of PFAS and adherence to three predefined dietary patterns (a WHO recommended diet, a Mediterranean-like diet, and a Low-Carbohydrate High-Protein (LCHP) diet) in an elderly Swedish population. Dietary data from 7-day food records and serum concentrations of PFAS were obtained from a 70-year-old Swedish population (n=844), the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The Healthy Diet Indicator score (based on WHO recommendations), the Mediterranean Diet Score and LCHP score were used to assess adherence. Multivariate linear regression was used to assess the associations between eight major PFAS and adherence to each dietary pattern. The WHO recommended diet was positively associated with perfluorohexane sulfonic acid (PFHxS). The LCHP diet was positively related to four out of eight PFAS; namely, perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA). The Mediterranean-like diet was positively associated with most PFAS; namely perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), PFHxS, PFNA, PFDA, and PFUnDA. All dietary patterns were positively associated with blood levels of PFAS. The highest body burden of PFAS was found in individuals with high adherence to a Mediterranean-like diet, whilst individuals who more closely followed the officially recommended diet displayed a lower body burden of these compounds. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Occurrence and spatial distribution of neutral perfluoroalkyl substances and cyclic volatile methylsiloxanes in the atmosphere of the Tibetan Plateau

    Directory of Open Access Journals (Sweden)

    X. Wang

    2018-06-01

    Full Text Available Due to their properties of bioaccumulation, toxicity, and long-range atmospheric transport, polyfluoroalkyl and perfluoroalkyl substances (PFASs and cyclic volatile methylsiloxanes (cVMSs are currently being considered as emerging persistent organic pollutants (POPs for regulation. To date, there are limited data on PFASs and cVMSs in the atmosphere of the Tibetan Plateau (TP, a remote environment which can provide information on global background conditions. Sorbent-impregnated polyurethane foam (SIP disc passive air samplers were therefore deployed for 3 months (May to July 2011 and 2013 at 16 locations across the TP. Using previously reported methods for estimating the air volume sampled by SIP discs, the derived atmospheric concentrations ranged as follows: 18–565 ng m−3 for ΣcVMS (including D3, D4, D5, and D6; 65–223 pg m−3 for fluorotelomer alcohols (ΣFTOHs; 1.2–12.8 pg m−3 for fluorinated sulfonamides (ΣFOSA; and 0.29–1.02 pg m−3 for fluorinated sulfonamidoethanols (ΣFOSE. The highest ΣcVMS occurred at Lhasa, the capital city of the TP, indicating the local contribution to the emerging pollutants. Higher levels of ΣFTOHs were observed at sites close to the transport channel of the Yarlung Tsangpo Grand Canyon, indicating possible long-range atmospheric transport (LRAT. Elevated concentrations of shorter-chain volatile PFAS precursors (4 : 2 FTOH and fluorobutane sulfonamidoethanol were found in most air samples, reflecting the shift in production from long- to short-chain PFASs in Asia. Overall, concentrations of emerging POPs at background sites of the TP were 1–3 orders of magnitude higher than those reported for legacy POPs.

  19. Review on enzyme-linked immunosorbent assays for sulfonamide residues in edible animal products.

    Science.gov (United States)

    Zhang, Hongyan; Wang, Shuo

    2009-10-31

    The current status of enzyme-linked immunosorbent assays (ELISAs) for sulfonamides in edible animal products is reviewed. The attention was focused on the design and synthesis of haptens, conjugation to carrier protein, production of antibody, application of homologous and heterologous systems, as well as the molecular modeling of the haptens and sulfonamides. Researches have shown that sulfonamides seem to be particularly resistant to attempts to produce broad specificity antibodies. By summarizing the available research on sulfonamide ELISAs, it is hoped that it can be considered as a basis for further investigation aimed at developing the most efficient approaches for detection.

  20. Spatial and temporal trends of poly- and perfluoroalkyl substances in fish fillets and water collected from pool 2 of the Upper Mississippi River.

    Science.gov (United States)

    Newsted, John L; Holem, Ryan; Hohenstein, Gary; Lange, Cleston; Ellefson, Mark; Reagen, William; Wolf, Susan

    2017-11-01

    In 2011, poly- and perfluoroalkyl substances (PFASs) were analyzed in surface water and fish fillet samples taken from Pool 2 of the Upper Mississippi River, a 33-mile stretch inclusive of the Minneapolis/St. Paul, Minnesota (USA) metropolitan area. Approximately 100 each of bluegill, freshwater drum, smallmouth bass, and white bass were sampled within the study area. Surface water samples were also collected from each of the 10 sampling reaches established for the study. Water and fillet samples were analyzed for perfluorinated carboxylic acids (C4-C12), perfluorinated sulfonic acids (C4, C6, and C8), and perfluorooctane sulfonamide. Perfluorooctane sulfonate (PFOS) was observed with the greatest frequency in fish fillets and ranged from 3.0 to 760 ng/g wet weight. Mean (geometric) PFOS concentrations in bluegill, freshwater drum, smallmouth bass, and white bass were 20, 28, 29, and 58 ng/g wet weight, respectively. When compared with fish data collected in 2009, a significant reduction (p fish PFOS concentrations are consistent with ongoing efforts to effectively control sources of PFASs to the Mississippi River. Environ Toxicol Chem 2017;36:3138-3147. © 2017 SETAC. © 2017 SETAC.

  1. Atmospheric concentrations and trends of poly- and perfluoroalkyl substances (PFAS) and volatile methyl siloxanes (VMS) over 7 years of sampling in the Global Atmospheric Passive Sampling (GAPS) network.

    Science.gov (United States)

    Rauert, Cassandra; Shoieb, Mahiba; Schuster, Jasmin K; Eng, Anita; Harner, Tom

    2018-07-01

    Poly- and per-fluoroalkyl substances (PFAS) and volatile methyl siloxanes (VMS) were monitored at 21 sites in the Global Atmospheric Passive Sampling (GAPS) Network. Atmospheric concentrations previously reported from 2009 were compared to concentrations measured at these sites in 2013 and 2015, to assess trends over 7 years of monitoring. Concentrations of the fluorotelomer alcohols (FTOHs) and fluorinated sulfonamides and sulfonamidoethanols (FOSAs and FOSEs) were stable at these sites from 2009 to 2015 with no significant difference (p > 0.05) in concentrations. Elevated concentrations of all the neutral PFAS were detected at the urban sites as compared to the polar/background sites. The perfluorosulfonic acids (PFSAs), meanwhile, saw a significant increase (p  0.05). Concentrations of the PFSAs and the PFCAs were similar at all location types, showing the global reach of these persistent compounds. Concentrations of the cyclic VMS (cVMS) were at least an order of magnitude higher than the linear VMS (lVMS) and the PFAS. Octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5) and dodecamethylcyclohexasiloxane (D6) saw a weak significant increase in concentrations from 2009 to 2013 (p < 0.05), however, hexamethylcyclotrisiloxane (D3) had a strong significant decrease in concentrations from 2009 to 2015 (p < 0.01). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Biosolid-borne tetracyclines and sulfonamides in plants.

    Science.gov (United States)

    Mathews, Shiny; Reinhold, Dawn

    2013-07-01

    Tetracyclines and sulfonamides used in human and animal medicine are released to terrestrial ecosystems from wastewater treatment plants or by direct manure application. The interactions between plants and these antibiotics are numerous and complex, including uptake and accumulation, phytometabolism, toxicity responses, and degradation in the rhizosphere. Uptake and accumulation of antibiotics have been studied in plants such as wheat, maize, potato, vegetables, and ornamentals. Once accumulated in plant tissue, organic contaminants can be metabolized through a sequential process of transformation, conjugation through glycosylation and glutathione pathways, and ultimately sequestration into plant tissue. While studies have yet to fully elucidate the phytometabolism of tetracyclines and sulfonamides, an in-depth review of plant and mammalian studies suggest multiple potential transformation and conjugation pathways for tetracyclines and sulfonamides. The presence of contaminants in the vicinity or within the plants can elicit stress responses and defense mechanisms that can help tolerate the negative effects of contaminants. Antibiotics can change microbial communities and enzyme activity in the rhizosphere, potentially inducing microbial antibiotic resistance. On the other hand, the interaction of microbes and root exudates on pharmaceuticals in the rhizosphere can result in degradation of the parent molecule to less toxic compounds. To fully characterize the environmental impacts of increased antibiotic use in human medicine and animal production, further research is essential to understand the effects of different antibiotics on plant physiology and productivity, uptake, translocation, and phytometabolism of antibiotics, and the role of antibiotics in the rhizosphere.

  3. Bioaccumulation of perfluoroalkyl carboxylates (PFCAs) and perfluoroalkane sulfonates (PFSAs) by earthworms (Eisenia fetida) in soil

    International Nuclear Information System (INIS)

    Zhao, Shuyan; Zhu, Lingyan; Liu, Li; Liu, Zhengtao; Zhang, Yahui

    2013-01-01

    Earthworms were exposed to artificially contaminated soils with ten perfluoroalkyl substances (PFASs). PFASs with longer perfluorinated carbon chain displayed higher uptake rate coefficients (k u ), longer half-life (t 1/2 ) and time to steady-state (t ss ) but lower elimination rate coefficients (k e ) than the shorter ones. Similarly, perfluorosulfonates acids (PFSAs) displayed higher k u , longer t 1/2 and t ss but lower k e than perflurocarboxylic acids (PFCAs) with the same perfluorinated chain length. All the studied PFASs, including those with seven or less perfluorinated carbons, were bioaccumulated in the earthworms and the biota-to-soil accumulation factors (BSAFs) increased with perfluorinated carbon chain length and were greater for PFSAs than for PFCAs of equal perfluoroalkyl chain length. The BSAFs were found to be dependent on the concentrations of PFASs in soil and decreased as the level of PFASs in soil increased. -- Highlights: •PFASs with seven or less perfluoroalkyl carbons were bioaccumulated in earthworm. •The BSAFs of PFASs in earthworm increased with perfluoroalkyl chain length. •The BSAFs of PFSAs were greater than PFCAs of equal perfluoroalkyl chain length. •The k u increased with perfluorinated chain length while k e decreased. •The BSAFs of PFASs decreased as their concentrations in soil increased. -- Perfluoroalkyl substances (PFASs) can be effectively bioaccumulated in earthworms including those with seven or less perfluoroalkyl carbon chain length

  4. A Class of Effective of Decarboxylative Perfluoroalkylating Reagents: [(phen)2Cu](O2CRF)

    KAUST Repository

    Huang, Yangjie

    2016-04-13

    This article describes the invention of a class of effective reagents [(phen)2Cu](O2CRF) (1) for the decarboxylative perfluoroalkylation of aryl and heteroaryl halides. Treatment of the copper tert-butyloxide with phenanthroline ligands, with subsequent addition of perfluorocarboxylic acids afforded the air-stable copper(I) perfluorocarboxylato complexes 1. These complexes reacted with a variety of aryl and heteroaryl halides to form perfluoroalkyl(hetero)arenes in moderate to high yields. Computational studies suggested that the coordination of the second phen ligand may reduce the energy barrier for the decarboxylation of perfluorocarboxylate to facilitate the perfluoroalkylation.

  5. A Class of Effective of Decarboxylative Perfluoroalkylating Reagents: [(phen)2Cu](O2CRF)

    KAUST Repository

    Huang, Yangjie; Ajitha, Manjaly John; Huang, Kuo-Wei; Zhang, Zhongxing; Weng, Zhiqiang

    2016-01-01

    This article describes the invention of a class of effective reagents [(phen)2Cu](O2CRF) (1) for the decarboxylative perfluoroalkylation of aryl and heteroaryl halides. Treatment of the copper tert-butyloxide with phenanthroline ligands, with subsequent addition of perfluorocarboxylic acids afforded the air-stable copper(I) perfluorocarboxylato complexes 1. These complexes reacted with a variety of aryl and heteroaryl halides to form perfluoroalkyl(hetero)arenes in moderate to high yields. Computational studies suggested that the coordination of the second phen ligand may reduce the energy barrier for the decarboxylation of perfluorocarboxylate to facilitate the perfluoroalkylation.

  6. Bioaccumulation and uptake routes of perfluoroalkyl acids in Daphnia magna.

    Science.gov (United States)

    Dai, Zhineng; Xia, Xinghui; Guo, Jia; Jiang, Xiaoman

    2013-02-01

    Perfluoroalkyl acids (PFAs), one kind of emerging contaminants, have attracted great attentions in recent years. However, the study about their bioaccumulation mechanism remains scarce. In this research, the bioaccumulation of six kinds of PFAs in water flea Daphnia magna was studied. The uptake rates of PFAs in D. magna ranged from 178 to 1338 L kg(-1) d(-1), and they increased with increasing perfluoroalkyl chain length; the elimination rates ranged from 0.98 to 2.82 d(-1). The bioaccumulation factors (BAFs) of PFAs ranged from 91 to 380 L kg(-1) in wet weight after 25 d exposure; they increased with increasing perfluoroalkyl chain length and had a significant positive correlation with the n-octanol/water partition coefficients (logK(ow)) of PFAs (pPFAs plays an important role in their bioaccumulation. The BAFs almost kept constant when the PFA concentrations in aqueous phase increased from 1 to 10 μg L(-1). Scenedesmus subspicatus, as the food of D. magna, did not significantly affect the bioaccumulation of PFAs by D. magna. Furthermore, the body burden of PFAs in the dead D. magna was 1.08-2.52 times higher than that in the living ones, inferring that the body surface sorption is a main uptake route of PFAs in D. magna. This study suggested that the bioaccumulation of PFAs in D. magna is mainly controlled by their partition between organisms and water; further research should be conducted to study the intrinsic mechanisms, especially the roles of protein and lipid in organisms. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Perfluoroalkylated substances (PFAS) affect oxidative stress biomarkers in vitro

    DEFF Research Database (Denmark)

    Wielsøe, Maria; Long, Manhai; Ghisari, Mandana

    2015-01-01

    Perfluoroalkylated substances (PFAS) have been widely used since 1950s and humans are exposed through food, drinking water, consumer products, dust, etc. The long-chained PFAS are persistent in the environment and accumulate in wildlife and humans. They are suspected carcinogens and a potential...... mode of action is through generation of oxidative stress. Seven long-chained PFAS found in human serum were investigated for the potential to generate reactive oxygen species (ROS), induce DNA damage and disturb the total antioxidant capacity (TAC). The tested PFAS were perfluorohexane sulfonate (PFHx...

  8. Efficient Generic Functional Programming

    NARCIS (Netherlands)

    Alimarine, A.; Smetsers, J.E.W.

    2005-01-01

    Generic functions are defined by induction on the structural representation of types. As a consequence, by defining just a single generic operation, one acquires this operation over any particular data type. An instance on a specific type is generated by interpretation of the type's structure. A

  9. Optimizing Generic Functions

    NARCIS (Netherlands)

    Alimarine, A.; Smetsers, J.E.W.

    2004-01-01

    Generic functions are defined by induction on the structural representation of types. As a consequence, by defining just a single generic operation, one acquires this operation over any particular type. An instance on a specific type is generated by interpretation of the type's structure. A direct

  10. Rapid trifluoromethylation and perfluoroalkylation of five-membered heterocycles by photoredox catalysis in continuous flow.

    Science.gov (United States)

    Straathof, Natan J W; Gemoets, Hannes P L; Wang, Xiao; Schouten, Jaap C; Hessel, Volker; Noël, Timothy

    2014-06-01

    Trifluoromethylated and perfluoroalkylated heterocycles are important building blocks for the synthesis of numerous pharmaceutical products, agrochemicals and are widely applied in material sciences. To date, trifluoromethylated and perfluoroalkylated hetero-aromatic systems can be prepared utilizing visible light photoredox catalysis methodologies in batch. While several limitations are associated with these batch protocols, the application of microflow technology could greatly enhance and intensify these reactions. A simple and straightforward photocatalytic trifluoromethylation and perfluoroalkylation method has been developed in continuous microflow, using commercially available photocatalysts and microflow components. A selection of five-membered hetero-aromatics were successfully trifluoromethylated (12 examples) and perfluoroalkylated (5 examples) within several minutes (8-20 min). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Estrogenic Activity of Perfluoroalkyl Acids in Juvenile Rainbow Trout (Oncorhynchus Mykiss)

    Science.gov (United States)

    The potential estrogenic activity of perfluoroalkyl acids (PFAAs) was determined using separate screening and dose response studies with juvenile rainbow trout (Oncorhynchus mykiss). Results of this study indicate that some PFAAs may act as estrogens in fish.

  12. Perfluoroalkyl substances measured in breast milk and child neuropsychological development in a Norwegian birth cohort study

    NARCIS (Netherlands)

    Forns, J.; Iszatt, N.; White, R.A.; Mandal, S.; Sabaredzovic, A.; Lamoree, M.H.; Thomsen, C.; Haug, L.S.; Stigum, H.; Eggesbo, M.

    2015-01-01

    Perfluoroalkyl substances (PFASs) are chemicals with potential neurotoxic effects although the current evidence is still limited. This study investigated the association between perinatal exposure to perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) and neuropsychological

  13. The developmental toxicity of perfluoroalkyl acids and their derivatives

    International Nuclear Information System (INIS)

    Lau, Christopher; Butenhoff, John L.; Rogers, John M.

    2004-01-01

    Perfluoroalkyl acids such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) have applications in numerous industrial and consumer products. Although the toxicology of some of these compounds has been investigated in the past, the widespread prevalence of PFOS and PFOA in humans, as demonstrated in recent bio-monitoring studies, has drawn considerable interest from the public and regulatory agencies as well as renewed efforts to better understand the hazards that may be inherent in these compounds. This review provides a brief overview of the perfluoroalkyl chemicals and a summary of the available information on the developmental toxicity of the eight-carbon compounds, PFOS and PFOA. Although the teratological potentials of some of these chemicals had been studied in the past and the findings were generally unremarkable, results from recent postnatal studies on developmental and reproductive indices have prompted consideration of their relevance to human health risk. Based on current understanding of the developmental effects of PFOS and PFOA in rodents, several avenues of research are suggested that would further support the risk assessment of these perfluorinated organic chemicals

  14. Hazard of Sulfonamides and Detection Technology Research Progress

    Science.gov (United States)

    Jiang, Jiahui; Wang, Guangyu

    2017-12-01

    As a kind of widely used antibiotic with typical characteristics, sulfonamides have been greatly applied in clinical medicine for long time. It can’t be effectively treated by pollutant disposal system during pharmaceutical process and utilization and will be discharged into natural environment to be one of the antibiotics with great effect. This kind of substance is difficult to be biodegraded and will be easy to accumulate in the environment, generating huge eco-toxicological effect with significant mutagenicity and teratogenic effect. It is the severe threat for ecological balance, human health and drinking water safety. Its environmental behavior and detection technology attract extensive attention home and abroad.

  15. [Interaction Between Sulfonamide Antibiotics Fates and Chicken Manure Composting].

    Science.gov (United States)

    Lin, Hui; Wang, Jian-mei; Sun, Wan-chun; Fu, Jian-rong; Chen, Hong-jin; Ma, Jun-wei

    2016-05-15

    Based on aerobic manure composting with or without the addition of a mixture of sulfadimethoxine SM2 and sulfamonomethoxine SMM (1:1, m/m), changes in the physic-chemical properties of manure compost, the microbial community physiological profiles, the antibiotics concentration and the abundances of five antibiotic resistance genes (ARGs) during the composting were tracked. The results indicated that the introduction of sulfonamide antibiotics led to inhibition on the basal respiration of manure compost during the early composting period, delayed the formation of thermophilic temperature and reduced the conversion of nutrients such as organic matter, ammonia nitrogen and nitrate nitrogen. Meanwhile, the introduction of sulfonamide antibiotics dramatically affected the physiological profile of microbial community in manure in the middle stage of composting. HPLC-MS/MS results showed that both SMM and SM2 in manure were completely degraded within 14 days, while the degradation rate of SMM was faster than that of SM2. For both composting treatments with or without addition of exogenous antibiotics, the relative abundance of sull and sul2 showed an initial decline in the first 14 or 21 days and a slight increase thereafter. The addition of exogenous antibiotics showed insignificant enhancement on increasing the relative abundance of sul1 and IntI1 in manure, but resulted in an apparent increase in sul2 relative abundance. Although the fates of tetQ and tetW during composting were different from that of sulfonamide ARGs, the introduction of sulfonamide antibiotics into manure increased the relative abundance of tetracycline ARGs. Redundancy analysis indicated that composting temperature correlated negatively with sul1, sul2 and IntI1 relative abundance in manure but had no obvious relationship with tetQ and tetW relative abundance. All the ARGs detected in this work correlated negatively with C/N ratio and the nitrate nitrogen concentration of manure compost but

  16. Generic antibiotics in Japan.

    Science.gov (United States)

    Fujimura, Shigeru; Watanabe, Akira

    2012-08-01

    Generic drugs have been used extensively in many developed countries, although their use in Japan has been limited. Generic drugs reduce drug expenses and thereby national medical expenditure. Because generic drugs provide advantages for both public administration and consumers, it is expected that they will be more widely used in the future. However, the diffusion rate of generic drugs in Japan is quite low compared with that of other developed countries. An investigation on generic drugs conducted by the Ministry of Health, Labour and Welfare in Japan revealed that 17.2 % of doctors and 37.2 % of patients had not used generic drugs. The major reasons for this low use rate included distrust of off-patent products and lower drug price margin compared with the brand name drug. The generic drugs available in the market include external drugs such as wet packs, antihypertensive agents, analgesics, anticancer drugs, and antibiotics. Among them, antibiotics are frequently used in cases of acute infectious diseases. When the treatment of these infections is delayed, the infection might be aggravated rapidly. The pharmacokinetics-pharmacodynamics (PK-PD) theory has been adopted in recent chemotherapy, and in many cases, the most appropriate dosage and administration of antibiotics are determined for individual patients considering renal function; high-dosage antibiotics are used preferably for a short duration. Therefore, a highly detailed antimicrobial agent is necessary. However, some of the generic antibiotics have less antibacterial potency or solubility than the brand name products. We showed that the potency of the generic products of vancomycin and teicoplanin is lower than that of the branded drugs by 14.6 % and 17.3 %, respectively. Furthermore, we confirmed that a generic meropenem drug for injection required about 82 s to solubilize in saline, whereas the brand product required only about 21 s. It was thought that the cause may be the difference in size of bulk

  17. Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay.

    Science.gov (United States)

    Bach, Cathrine Carlsen; Henriksen, Tine Brink; Bossi, Rossana; Bech, Bodil Hammer; Fuglsang, Jens; Olsen, Jørn; Nohr, Ellen Aagaard

    2015-01-01

    In studies of perfluoroalkyl acids, the validity and comparability of measured concentrations may be affected by differences in the handling of biospecimens. We aimed to investigate whether measured plasma levels of perfluoroalkyl acids differed between blood samples subjected to delay and transportation prior to processing and samples with immediate processing and freezing. Pregnant women recruited at Aarhus University Hospital, Denmark, (n = 88) provided paired blood samples. For each pair of samples, one was immediately processed and plasma was frozen, and the other was delayed and transported as whole blood before processing and freezing of plasma (similar to the Danish National Birth Cohort). We measured 12 perfluoroalkyl acids and present results for compounds with more than 50% of samples above the lower limit of quantification. For samples taken in the winter, relative differences between the paired samples ranged between -77 and +38% for individual perfluoroalkyl acids. In most cases concentrations were lower in the delayed and transported samples, e.g. the relative difference was -29% (95% confidence interval -30; -27) for perfluorooctane sulfonate. For perfluorooctanoate there was no difference between the two setups [corresponding estimate 1% (0, 3)]. Differences were negligible in the summer for all compounds. Transport of blood samples and processing delay, similar to conditions applied in some large, population-based studies, may affect measured perfluoroalkyl acid concentrations, mainly when outdoor temperatures are low. Attention to processing conditions is needed in studies of perfluoroalkyl acid exposure in humans.

  18. Practicing the Generic (City)

    DEFF Research Database (Denmark)

    Hansen, Lone Koefoed

    2010-01-01

    Flanagan proposes that most locative media artworks neglect the particularities of spaces, their historical and political layers. Koolhaas, on the other hand, states that all urban areas are alike, that we are facing a global Generic City. The paper analyses digital media artist Esther Polak......’s NomadicMILK project in light of the generic and particular properties of space as laid out by Flanagan and Koolhaas in order to discuss the possible reconfiguring practices of locative media....

  19. Enzymatic Transformation and Bonding of Sulfonamide Antibiotics to Model Humic Substances

    Directory of Open Access Journals (Sweden)

    J. Schwarz

    2015-01-01

    Full Text Available Sulfonamides are consumed as pharmaceutical antibiotics and reach agricultural soils with excreta used as fertilizer. Subsequently, nonextractable residues rapidly form in soil, which has been researched in a couple of studies. To further elucidate conditions, strength, and mechanisms of the fixation to soil humic substances, three selected sulfonamides were investigated using the biochemical oligomerization of substituted phenols as a model for the humification process. Catechol, guaiacol, and vanillin were enzymatically reacted using laccase from Trametes versicolor. In the presence of the substituted phenols alone, the concentration of sulfonamides decreased. This decrease was even more pronounced when additional laccase was present. Upon the enzymatic oligomerization of the substituted phenols to a humic-like structure the sulfonamides were sorbed, transformed, sequestered, and nonextractable bound. Sulfonamides were transformed depending on their molecular properties. Fractions of different bonding strength were determined using a sequential extraction procedure. Isolated nonextractable products were analyzed by chromatographic, spectroscopic, and calorimetric methods to identify coupling and bonding mechanisms of the sulfonamides. Differential scanning calorimetry measurements suggested cross-linking of such incorporated sulfonamides in humic oligomers. Nuclear magnetic resonance spectroscopy measurements showed clear differences between the vanillin-sulfapyridine oligomer and the parent sulfapyridine indicating bound residue formation through covalent binding.

  20. Development of flow-through and dip-stick immunoassays for screening of sulfonamide residues.

    Science.gov (United States)

    Zhang, Hongyan; Zhang, Yan; Wang, Shuo

    2008-08-20

    Two formats of membrane-based competitive enzyme immunoassays (flow-through and dip-stick) have been developed for the screening of sulfonamide residues in pig muscle and milk. Membrane was coated with anti-sulfonamide antibody and a sulfonamide hapten D2-horseradish peroxidase (HRP) conjugant was used as the labeled antigen for competitive assay of sulfonamides. Visual detection limits of the flow-through or dip-stick assay were 1-5 microg L(-1) or 1-10 microg L(-1) in buffer for seven sulfonamides, respectively. Assay validation was performed using samples spiked with single sulfonamide, spiked samples were tested using the developed strip assays and results were compared with those obtained by a validated high-performance liquid chromatograph (HPLC) method. Results showed that the two strip assays were correlated well with HPLC, respectively. With assay times of 5 min (flow-through) and 15 min (dip-stick), these rapid tests could offer simple, rapid and cost-effective on-site screening tools to detect sulfonamides in pig muscle (flow-through or dip-stick) or milk (only dip-stick).

  1. Circulating levels of perfluoroalkyl substances are associated with dietary patterns – A cross sectional study in elderly Swedish men and women

    Energy Technology Data Exchange (ETDEWEB)

    Sjogren, Per, E-mail: per.sjogren@pubcare.uu.se [Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala (Sweden); Montse, Rachel, E-mail: charlesrachel@gmail.com [Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala (Sweden); Lampa, Erik, E-mail: erik.lampa@ucr.uu.se [Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala (Sweden); Salihovic, Samira, E-mail: samira.salihovic@medsci.uu.se [Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala (Sweden); Bavel, Bert van, E-mail: Bert.VanBavel@oru.se [MTM Research Centre, Örebro University, Örebro (Sweden); Lind, Lars, E-mail: lars.lind@medsci.uu.se [Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala (Sweden); Lind, P. Monica, E-mail: monica.lind@medsci.uu.se [Department of Medical Sciences, Occupational and Environmental Medicine, Uppsala University, Uppsala (Sweden)

    2016-10-15

    Background: In our daily life, we are exposed to perfluoroalkyl substances (PFAS) with possible health implications. The main exposure route for these substances is diet but comparative studies on how dietary habits influence exposure are lacking. Objectives: To examine the relations between blood levels of PFAS and adherence to three predefined dietary patterns (a WHO recommended diet, a Mediterranean-like diet, and a Low-Carbohydrate High-Protein (LCHP) diet) in an elderly Swedish population. Methods: Dietary data from 7-day food records and serum concentrations of PFAS were obtained from a 70-year-old Swedish population (n=844), the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The Healthy Diet Indicator score (based on WHO recommendations), the Mediterranean Diet Score and LCHP score were used to assess adherence. Multivariate linear regression was used to assess the associations between eight major PFAS and adherence to each dietary pattern. Results: The WHO recommended diet was positively associated with perfluorohexane sulfonic acid (PFHxS). The LCHP diet was positively related to four out of eight PFAS; namely, perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA). The Mediterranean-like diet was positively associated with most PFAS; namely perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), PFHxS, PFNA, PFDA, and PFUnDA. Conclusions: All dietary patterns were positively associated with blood levels of PFAS. The highest body burden of PFAS was found in individuals with high adherence to a Mediterranean-like diet, whilst individuals who more closely followed the officially recommended diet displayed a lower body burden of these compounds. - Highlights: • Perfluoroalkyl substances (PFAS) quantified in blood of 70-y-old Swedish subjects. • Adherence to predefined dietary patterns was associated with circulating PFAS. • A

  2. Circulating levels of perfluoroalkyl substances are associated with dietary patterns – A cross sectional study in elderly Swedish men and women

    International Nuclear Information System (INIS)

    Sjogren, Per; Montse, Rachel; Lampa, Erik; Salihovic, Samira; Bavel, Bert van; Lind, Lars; Lind, P. Monica

    2016-01-01

    Background: In our daily life, we are exposed to perfluoroalkyl substances (PFAS) with possible health implications. The main exposure route for these substances is diet but comparative studies on how dietary habits influence exposure are lacking. Objectives: To examine the relations between blood levels of PFAS and adherence to three predefined dietary patterns (a WHO recommended diet, a Mediterranean-like diet, and a Low-Carbohydrate High-Protein (LCHP) diet) in an elderly Swedish population. Methods: Dietary data from 7-day food records and serum concentrations of PFAS were obtained from a 70-year-old Swedish population (n=844), the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. The Healthy Diet Indicator score (based on WHO recommendations), the Mediterranean Diet Score and LCHP score were used to assess adherence. Multivariate linear regression was used to assess the associations between eight major PFAS and adherence to each dietary pattern. Results: The WHO recommended diet was positively associated with perfluorohexane sulfonic acid (PFHxS). The LCHP diet was positively related to four out of eight PFAS; namely, perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA) and perfluoroundecanoic acid (PFUnDA). The Mediterranean-like diet was positively associated with most PFAS; namely perfluorooctanoic acid (PFOA), perfluorooctane sulfonamide (PFOSA), PFHxS, PFNA, PFDA, and PFUnDA. Conclusions: All dietary patterns were positively associated with blood levels of PFAS. The highest body burden of PFAS was found in individuals with high adherence to a Mediterranean-like diet, whilst individuals who more closely followed the officially recommended diet displayed a lower body burden of these compounds. - Highlights: • Perfluoroalkyl substances (PFAS) quantified in blood of 70-y-old Swedish subjects. • Adherence to predefined dietary patterns was associated with circulating PFAS. • A

  3. Molecular dynamics-assisted pharmacophore modeling of caspase-3-isatin sulfonamide complex: Recognizing essential intermolecular contacts and features of sulfonamide inhibitor class for caspase-3 binding.

    Science.gov (United States)

    Kumar, Sivakumar Prasanth; Patel, Chirag N; Jha, Prakash C; Pandya, Himanshu A

    2017-12-01

    The identification of isatin sulfonamide as a potent small molecule inhibitor of caspase-3 had fuelled the synthesis and characterization of the numerous sulfonamide class of inhibitors to optimize for potency. Recent works that relied on the ligand-based approaches have successfully shown the regions of optimizations for sulfonamide scaffold. We present here molecular dynamics-based pharmacophore modeling of caspase-3-isatin sulfonamide crystal structure, to elucidate the essential non-covalent contacts and its associated pharmacophore features necessary to ensure caspase-3 optimal binding. We performed 20ns long dynamics of this crystal structure to extract global conformation states and converted into structure-based pharmacophore hypotheses which were rigorously validated using an exclusive focussed library of experimental actives and inactives of sulfonamide class by Receiver Operating Characteristic (ROC) statistic. Eighteen structure-based pharmacophore hypotheses with better sensitivity and specificity measures (>0.6) were chosen which collectively showed the role of pocket residues viz. Cys163 (S 1 sub-site; required for covalent and H bonding with Michael acceptor of inhibitors), His121 (S 1 ; π stack with bicyclic isatin moiety), Gly122 (S 1 ; H bond with carbonyl oxygen) and Tyr204 (S 2 ; π stack with phenyl group of the isatin sulfonamide molecule) as stringent binding entities for enabling caspase-3 optimal binding. The introduction of spatial pharmacophore site points obtained from dynamics-based pharmacophore models in a virtual screening strategy will be helpful to screen and optimize molecules belonging to sulfonamide class of caspase-3 inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Scripting XML with Generic Haskell

    NARCIS (Netherlands)

    Atanassow, F.; Clarke, D.; Jeuring, J.T.

    2003-01-01

    A generic program is written once and works on values of many data types. Generic Haskell is a recent extension of the functional programming language Haskell that supports generic programming. This paper discusses how Generic Haskell can be used to implement XML tools whose behaviour depends on

  5. Scripting XML with Generic Haskell

    NARCIS (Netherlands)

    Atanassow, F.; Clarke, D.; Jeuring, J.T.

    2007-01-01

    A generic program is written once and works on values of many data types. Generic Haskell is a recent extension of the functional programming language Haskell that supports generic programming. This paper discusses how Generic Haskell can be used to implement XML tools whose behaviour depends on

  6. Perfluoroalkyl Acids in Maternal Serum and Indices of Fetal Growth

    DEFF Research Database (Denmark)

    Bach, Cathrine C; Bech, Bodil H; Nohr, Ellen A

    2015-01-01

    BACKGROUND: Previous studies indicated an association between intrauterine exposure to perfluorooctane sulfonate (PFOS) or perfluorooctanoate (PFOA) and lower birth weight. However, these perfluoroalkyl acids (PFAAs) have to some extent been substituted by other compounds on which little is known...... was restricted to term births (n=1426). For PFOS, the birth weight estimates for the highest versus lowest quartile were -50 [95 % CI: -123; 23] g in all births and -62 [95 % CI: -126; 3] g in term births. For the other PFAAs, the direction of the associations was inconsistent, and no overall association...... with birth weight was apparent. No PFAAs were associated with birth length or head circumference at birth. CONCLUSIONS: Overall, we did not find strong or consistent associations between PFAAs and birth weight or other indices of fetal growth, though estimated mean birth weights were lower among those...

  7. Sorption of perfluoroalkyl substances to two types of minerals.

    Science.gov (United States)

    Hellsing, Maja S; Josefsson, Sarah; Hughes, Arwel V; Ahrens, Lutz

    2016-09-01

    The sorption of perfluoroalkyl substances (PFASs) was investigated for two model soil mineral surfaces, alumina (Al2O3) and silica (SiO2), on molecular level using neutron scattering. The PFASs were selected (i.e. perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorooctane sulfonic acid (PFOS)) to examine the role of hydrophobic chain length and hydrophilic functional group on their sorption behaviour. All four PFASs were found to sorb to alumina surface (positively charged) forming a hydrated layer consisting of 50% PFASs. The PFAS solubility limit, which decrease with chain length, was found to strongly influence the sorption behaviour. The sorbed PFAS layer could easily be removed by gentle rinsing with water, indicating release upon rainfall in the environment. No sorption was observed for PFOA and PFOS at silica surface (negatively charged), showing electrostatic interaction being the driving force in the sorption process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Generic phytosanitary irradiation treatments

    International Nuclear Information System (INIS)

    Hallman, Guy J.

    2012-01-01

    The history of the development of generic phytosanitary irradiation (PI) treatments is discussed beginning with its initial proposal in 1986. Generic PI treatments in use today are 150 Gy for all hosts of Tephritidae, 250 Gy for all arthropods on mango and papaya shipped from Australia to New Zealand, 300 Gy for all arthropods on mango shipped from Australia to Malaysia, 350 Gy for all arthropods on lychee shipped from Australia to New Zealand and 400 Gy for all hosts of insects other than pupae and adult Lepidoptera shipped to the United States. Efforts to develop additional generic PI treatments and reduce the dose for the 400 Gy treatment are ongoing with a broad based 5-year, 12-nation cooperative research project coordinated by the joint Food and Agricultural Organization/International Atomic Energy Agency Program on Nuclear Techniques in Food and Agriculture. Key groups identified for further development of generic PI treatments are Lepidoptera (eggs and larvae), mealybugs and scale insects. A dose of 250 Gy may suffice for these three groups plus others, such as thrips, weevils and whiteflies. - Highlights: ► The history of phytosanitary irradiation (PI) treatments is given. ► Generic PI treatments in use today are discussed. ► Suggestions for future research are presented. ► A dose of 250 Gy for most insects may suffice.

  9. Generic robot architecture

    Science.gov (United States)

    Bruemmer, David J [Idaho Falls, ID; Few, Douglas A [Idaho Falls, ID

    2010-09-21

    The present invention provides methods, computer readable media, and apparatuses for a generic robot architecture providing a framework that is easily portable to a variety of robot platforms and is configured to provide hardware abstractions, abstractions for generic robot attributes, environment abstractions, and robot behaviors. The generic robot architecture includes a hardware abstraction level and a robot abstraction level. The hardware abstraction level is configured for developing hardware abstractions that define, monitor, and control hardware modules available on a robot platform. The robot abstraction level is configured for defining robot attributes and provides a software framework for building robot behaviors from the robot attributes. Each of the robot attributes includes hardware information from at least one hardware abstraction. In addition, each robot attribute is configured to substantially isolate the robot behaviors from the at least one hardware abstraction.

  10. Integration of generic issues

    International Nuclear Information System (INIS)

    Thatcher, D.

    1989-01-01

    The NRC has recognized the need to integrate generic issues (GIs). The GI process includes a number of phases, all of which should recognize the potential for overlap and conflict among related issues. In addition to the issues themselves, other related NRC and industry programs and activities need to be factored into the GI process. Integration has taken place, or is taking place, for a number of GIs. Each case of integration involves a specific set of circumstances and, as a result, the way in which integration proceeds can vary. This paper discusses the integration of issues in the generic issue process and provides a number of examples

  11. Rethinking generic skills

    Directory of Open Access Journals (Sweden)

    Roy Canning

    2013-10-01

    Full Text Available The paper provides a critical analysis of the notion of generic or transversal skillscontained with European Union policy discourses. The author presents a conceptualframework that challenges the idea that generic skills are universal, transferable andautonomous. An alternative analysis is put forward that argues the case forcontextualising skills and knowledge within particular understandings and cultures thatare more collective than individualistic in nature. The arguments are framed withinwider cross-disciplinary debates in linguistics, geosemiotics and social-cultural theoryand build upon an earlier paper exploring core skills in the UK (Canning, 2007.

  12. Modularity and three-dimensional isostructurality of novel synthons in sulfonamide-lactam cocrystals.

    Science.gov (United States)

    Bolla, Geetha; Mittapalli, Sudhir; Nangia, Ashwini

    2015-07-01

    The design of novel supramolecular synthons for functional groups relevant to drugs is an essential prerequisite for applying crystal engineering in the development of novel pharmaceutical cocrystals. It has been convincingly shown over the past decade that molecular level control and modulation can influence the physicochemical properties of drug cocrystals. Whereas considerable advances have been reported on the design of cocrystals for carboxylic acids and carboxamide functional groups, the sulfonamide group, which is a cornerstone of sulfa drugs, is relatively unexplored for reproducible heterosynthon-directed crystal engineering. The occurrence of synthons and isostructurality in sulfonamide-lactam cocrystals (SO2NH2⋯CONH hydrogen bonding) is analyzed to define a strategy for amide-type GRAS (generally recognized as safe) coformers with sulfonamides. Three types of supramolecular synthons are identified for the N-H donor of sulfonamide hydrogen bonding to the C=O acceptor of amide. Synthon 1: catemer synthon C 2 (1)(4) chain motif, synthon 2: dimer-cyclic ring synthon R 2 (2)(8)R 4 (2)(8) motifs, and synthon 3: dimer-catemer synthon of R 2 (2)(8)C 1 (1)(4)D notation. These heterosynthons of the cocrystals observed in this study are compared with the N-H⋯O dimer R 2 (2)(8) ring and C(4) chain motifs of the individual sulfonamide structures. The X-ray crystal structures of sulfonamide-lactam cocrystals exhibit interesting isostructurality trends with the same synthon being present. One-dimensional, two-dimensional and three-dimensional isostructurality in crystal structures is associated with isosynthons and due to their recurrence, novel heterosynthons for sulfonamide cocrystals are added to the crystal engineer's toolkit. With the predominance of sulfa drugs in medicine, these new synthons provide rational strategies for the design of binary and potentially ternary cocrystals of sulfonamides.

  13. Selective Access to Heterocyclic Sulfonamides and Sulfonyl Fluorides via a Parallel Medicinal Chemistry Enabled Method.

    Science.gov (United States)

    Tucker, Joseph W; Chenard, Lois; Young, Joseph M

    2015-11-09

    A sulfur-functionalized aminoacrolein derivative is used for the efficient and selective synthesis of heterocyclic sulfonyl chlorides, sulfonyl fluorides, and sulfonamides. The development of a 3-step parallel medicinal chemistry (PMC) protocol for the synthesis of pyrazole-4-sulfonamides effectively demonstrates the utility of this reagent. This reactivity was expanded to provide rapid access to other heterocyclic sulfonyl fluorides, including pyrimidines and pyridines, whose corresponding sulfonyl chlorides lack suitable chemical stability.

  14. Generic clearance values

    International Nuclear Information System (INIS)

    Bossio, M.C.; Muniz, C.C.

    2009-01-01

    This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document 'Safety Reports Series Nr 44' of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (author)

  15. Generic Clearance Values

    International Nuclear Information System (INIS)

    Bossio, M.C.; Muniz, C.C.

    2010-01-01

    This paper analyzes the Generic Clearance Values established for natural and artificial radionuclides with the objective of evaluating their degree of conservatism in views of adopting them into the regulatory body. Generic clearance values for natural radionuclides have been chosen by experts judgments as the optimum boundary between, on the one hand, the ubiquitous unmodified soil concentrations and, on the other hand, activity concentrations in ores, mineral sands, industrial residues and wastes. For artificial radionuclides the clearance levels have been derived from the scenarios postulated in the document Safety Reports Series 44 of the IAEA considering quantitative exemption criteria. A set of 8 scenarios were postulated covering external, ingestion and inhalation exposure pathways. For each radionuclide, the generic clearance level was derived as the more restrictive value obtained from the scenarios, that is the lowest ratio between the applicable individual dose and the dose per unit activity concentration (Bq/g). The individual dose was calculated by a formula depending on each scenario and pathway, with different parameters, such as exposure time, dosimetric factors, dilution factor, density of the material, geometric factors, etc. It was concluded that the basis and parameters used for the derivation of the generic clearance levels are quite conservative and therefore its the adoption in Argentina has been recommended. It is expected that their implementation will contribute to optimize the regulatory management system. (authors) [es

  16. Generic phytosanitary irradiation treatments

    Science.gov (United States)

    Hallman, Guy J.

    2012-07-01

    The history of the development of generic phytosanitary irradiation (PI) treatments is discussed beginning with its initial proposal in 1986. Generic PI treatments in use today are 150 Gy for all hosts of Tephritidae, 250 Gy for all arthropods on mango and papaya shipped from Australia to New Zealand, 300 Gy for all arthropods on mango shipped from Australia to Malaysia, 350 Gy for all arthropods on lychee shipped from Australia to New Zealand and 400 Gy for all hosts of insects other than pupae and adult Lepidoptera shipped to the United States. Efforts to develop additional generic PI treatments and reduce the dose for the 400 Gy treatment are ongoing with a broad based 5-year, 12-nation cooperative research project coordinated by the joint Food and Agricultural Organization/International Atomic Energy Agency Program on Nuclear Techniques in Food and Agriculture. Key groups identified for further development of generic PI treatments are Lepidoptera (eggs and larvae), mealybugs and scale insects. A dose of 250 Gy may suffice for these three groups plus others, such as thrips, weevils and whiteflies.

  17. Generic phytosanitary irradiation treatments

    Energy Technology Data Exchange (ETDEWEB)

    Hallman, Guy J [United States Department of Agriculture, Agricultural Research Service, Weslaco, TX (United States)

    2013-01-15

    The history of the development of generic phytosanitary irradiation (PI) treatments is discussed beginning with its initial proposal in 1986. Generic PI treatments in use today are 150 Gy for all hosts of Tephritidae, 250 Gy for all arthropods on mango and papaya shipped from Australia to New Zealand, 300 Gy for all arthropods on mango shipped from Australia to Malaysia, 350 Gy for all arthropods on lychee shipped from Australia to New Zealand and 400 Gy for all hosts of insects other than pupae and adult Lepidoptera shipped to the United States. Efforts to develop additional generic PI treatments and reduce the dose for the 400 Gy treatment are ongoing with a broad based 5-year, 12-nation cooperative research project coordinated by the joint Food and Agricultural Organization/International Atomic Energy Agency Program on Nuclear Techniques in Food and Agriculture. Key groups identified for further development of generic PI treatments are Lepidoptera (eggs and larvae), mealybugs and scale insects. A dose of 250 Gy may suffice for these three groups plus others, such as thrips, weevils and whiteflies. (author)

  18. The generic strategy trap.

    Science.gov (United States)

    Miller, D

    1992-01-01

    Management experts claim that for a company to thrive, it must concentrate on a single generic strategy--on one thing it does better than its rivals. But specialization also has its disadvantages. The author suggests that a broader, mixed approach may be preferable.

  19. Are perfluoroalkyl acids in waste water treatment plant effluents the result of primary emissions from the technosphere or of environmental recirculation?

    Science.gov (United States)

    Filipovic, Marko; Berger, Urs

    2015-06-01

    Wastewater treatment plants (WWTP) have been suggested to be one of the major pathways of perfluoroalkyl acids (PFAAs) from the technosphere to the aquatic environment. The origin of PFAAs in WWTP influents is either from current primary emissions or a result of recirculation of PFAAs that have been residing and transported in the environment for several years or decades. Environmental recirculation can then occur when PFAAs from the environment enter the wastewater stream in, e.g., tap water. In this study 13 PFAAs and perfluorooctane sulfonamide were analyzed in tap water as well as WWTP influent, effluent and sludge from three Swedish cities: Bromma (in the metropolitan area of Stockholm), Bollebygd and Umeå. A mass balance of the WWTPs was assembled for each PFAA. Positive mass balances were observed for PFHxA and PFOA in all WWTPs, indicating the presence of precursor compounds in the technosphere. With regard to environmental recirculation, tap water was an important source of PFAAs to the Bromma WWTP influent, contributing >40% for each quantified sulfonic acid and up to 30% for the carboxylic acids. The PFAAs in tap water from Bollebygd and Umeå did not contribute significantly to the PFAA load in the WWTP influents. Our results show that in order to estimate current primary emissions from the technosphere, it may be necessary to correct the PFAA emission rates in WWTP effluents for PFAAs present in tap water, especially in the case of elevated levels in tap water. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Generic and biosimilar medicines: quid?

    Directory of Open Access Journals (Sweden)

    Steven Simoens

    2012-12-01

    Full Text Available Once intellectual property protection, data and marketing exclusivity of reference medicines have expired, generic medicines and biosimilar medicines can enter the off-patent market. This market entry is conditional on the approval of marketing authorization, pricing and reimbursement. Given that there tends to be confusion surrounding generic and biosimilar medicines, this Editorial introduces basic concepts related to generic and biosimilar medicines and presents the different studies and articles included in this supplement dedicated to generic and biosimilar medicines.

  1. Generics Pricing: The Greek Paradox.

    Science.gov (United States)

    Karafyllis, Ioannis; Variti, Lamprini

    2017-01-01

    This paper explains and develops a methodological framework to help evaluate the performance of generic pharmaceutical policies and the correct evaluation of generics sales. Until today erroneous recording of generics does not help proper pricing and their penetration in the Greek market. This classifies Greece on the outliners in every study or comparison that is referred on papers or studies.

  2. Generic Reed Solomon Encorder

    Directory of Open Access Journals (Sweden)

    Petrus Mursanto

    2006-11-01

    Full Text Available Reed Solomon (RS codes is a mechanism to detect and correct burst of errors in data transmission and storage systems. It provides a solid introduction to foundation mathematical concept of Galois Field algebra and its application. With the development of digital hardware technology, the RS concepts were brought into reality, i.e. the implementation of RS codec chips. This paper presents the development steps of a generic RS encoder using VHDL. The encoder is able to handle generic width of data, variable length of information, number of error as well as variable form of primitive polynomial and generator polynomial used in the system. The design has been implemented for FPGA chip Xilinx XC3S200-5FT256 and has a better performance than commercially available equivalent encoder.

  3. Generic safety documentation model

    International Nuclear Information System (INIS)

    Mahn, J.A.

    1994-04-01

    This document is intended to be a resource for preparers of safety documentation for Sandia National Laboratories, New Mexico facilities. It provides standardized discussions of some topics that are generic to most, if not all, Sandia/NM facilities safety documents. The material provides a ''core'' upon which to develop facility-specific safety documentation. The use of the information in this document will reduce the cost of safety document preparation and improve consistency of information

  4. Comparison of generic-to-brand switchback patterns for generic and authorized generic drugs

    Science.gov (United States)

    Hansen, Richard A.; Qian, Jingjing; Berg, Richard; Linneman, James; Seoane-Vazquez, Enrique; Dutcher, Sarah K.; Raofi, Saeid; Page, C. David; Peissig, Peggy

    2018-01-01

    Background While generic drugs are therapeutically equivalent to brand drugs, some patients and healthcare providers remain uncertain about whether they produce identical outcomes. Authorized generics, which are identical in formulation to corresponding brand drugs but marketed as a generic, provide a unique post-marketing opportunity to study whether utilization patterns are influenced by perceptions of generic drugs. Objectives To compare generic-to-brand switchback rates between generics and authorized generics. Methods A retrospective cohort study was conducted using claims and electronic health records data from a regional U.S. healthcare system. Ten drugs with authorized generics and generics marketed between 1999 and 2014 were evaluated. Eligible adult patients received a brand drug during the 6 months preceding generic entry, and then switched to a generic or authorized generic. Patients in this cohort were followed for up to 30 months from the index switch date to evaluate occurrence of generic-to-brand switchbacks. Switchback rates were compared between patients on authorized generics versus generics using Kaplan-Meier curves and Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson comorbidity score, pre-index drug use characteristics, and pre-index healthcare utilization. Results Among 5,542 unique patients that switched from brand-to-generic or brand-to-authorized generic, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for authorized generics compared with generics (HR=0.86; 95% CI 0.65-1.15). The likelihood of switchback was higher for alendronate (HR=1.64; 95% CI 1.20-2.23) and simvastatin (HR=1.81; 95% CI 1.30-2.54) and lower for amlodipine (HR=0.27; 95% CI 0.17-0.42) compared with other drugs in the cohort. Conclusions Overall switchback rates were similar between authorized generic and generic drug users, indirectly supporting similar efficacy and tolerability profiles for

  5. Nitrotriazole- and imidazole-based amides and sulfonamides as antitubercular agents.

    Science.gov (United States)

    Papadopoulou, Maria V; Bloomer, William D; Rosenzweig, Howard S; Arena, Alexander; Arrieta, Francisco; Rebolledo, Joseph C J; Smith, Diane K

    2014-11-01

    Twenty-three 3-nitrotriazole-based and 2-nitroimidazole-based amides and sulfonamides were screened for antitubercular (anti-TB) activity in aerobic Mycobacterium tuberculosis H37Rv by using the BacTiter-Glo (BTG) microbial cell viability assay. In general, 3-nitrotriazole-based sulfonamides demonstrated anti-TB activity, whereas 3-nitrotriazole-based amides and 2-nitroimidazole-based amides and sulfonamides were inactive. Three 3-nitrotriazole-based sulfonamides (compounds 4, 2, and 7) demonstrated 50% inhibitory concentration (IC50), IC90, and MIC values of 0.38, 0.43, and 1.56 μM (compound 4), 0.57, 0.98, and 3.13 μM (compound 2), and 0.79, 0.87, and 3.13 μM (compound 7), respectively. For 3-nitrotriazole-based sulfonamides, anti-TB activity increased with lipophilicity, whereas the one-electron reduction potential (E1/2) did not play a role. 2-Nitroimidazole-based analogs, which were inactive in the BTG assay, were significantly more active in the low-oxygen assay and more active than the 3-nitrotriazoles. All active nitrotriazoles in the BTG assay were similarly active or more potent (lower MIC values) against resistant strains, with the exception of compounds 2, 3, 4, and 8, which demonstrated greater MIC values against isoniazid-resistant strains. Five 3-nitrotriazole-based sulfonamides demonstrated activity in infected murine J774 macrophages, causing log reductions similar to those seen with rifampin. However, some compounds caused toxicity in uninfected macrophages. In conclusion, the classes of 3-nitrotriazole-based amides and sulfonamides merit further investigation as potential antitubercular agents. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  6. Crystal structures of 4-meth-oxy-N-(4-methyl-phenyl)benzene-sulfonamide and N-(4-fluoro-phenyl)-4-meth-oxy-benzene-sulfonamide.

    Science.gov (United States)

    Rodrigues, Vinola Z; Preema, C P; Naveen, S; Lokanath, N K; Suchetan, P A

    2015-11-01

    Crystal structures of two N-(ar-yl)aryl-sulfonamides, namely, 4-meth-oxy-N-(4-methyl-phen-yl)benzene-sulfonamide, C14H15NO3S, (I), and N-(4-fluoro-phen-yl)-4-meth-oxy-benzene-sulfonamide, C13H12FNO3S, (II), were determined and analyzed. In (I), the benzene-sulfonamide ring is disordered over two orientations, in a 0.516 (7):0.484 (7) ratio, which are inclined to each other at 28.0 (1)°. In (I), the major component of the sulfonyl benzene ring and the aniline ring form a dihedral angle of 63.36 (19)°, while in (II), the planes of the two benzene rings form a dihedral angle of 44.26 (13)°. In the crystal structure of (I), N-H⋯O hydrogen bonds form infinite C(4) chains extended in [010], and inter-molecular C-H⋯πar-yl inter-actions link these chains into layers parallel to the ab plane. The crystal structure of (II) features N-H⋯O hydrogen bonds forming infinite one dimensional C(4) chains along [001]. Further, a pair of C-H⋯O inter-molecular inter-actions consolidate the crystal packing of (II) into a three-dimensional supra-molecular architecture.

  7. Determination of perfluoroalkyl carboxylic, sulfonic, and phosphonic acids in food.

    Science.gov (United States)

    Ullah, Shahid; Alsberg, Tomas; Vestergren, Robin; Berger, Urs

    2012-11-01

    A sensitive and accurate method was developed and validated for simultaneous analysis of perfluoroalkyl carboxylic acids, sulfonic acids, and phosphonic acids (PFPAs) at low picograms per gram concentrations in a variety of food matrices. The method employed extraction with acetonitrile/water and cleanup on a mixed-mode co-polymeric sorbent (C8 + quaternary amine) using solid-phase extraction. High-performance liquid chromatographic separation was achieved on a C18 column using a mobile phase gradient containing 5 mM 1-methyl piperidine for optimal chromatographic resolution of PFPAs. A quadrupole time-of-flight high-resolution mass spectrometer operating in negative ion mode was used as detector. Method detection limits were in the range of 0.002 to 0.02 ng g(-1) for all analytes. Sample preparation (extraction and cleanup) recoveries at a spiking level of 0.1 ng g(-1) to a baby food composite were in the range of 59 to 98 %. A strong matrix effect was observed in the analysis of PFPAs in food extracts, which was tentatively assigned to sorption of PFPAs to the injection vial in the solvent-based calibration standard. The method was successfully applied to a range of different food matrices including duplicate diet samples, vegetables, meat, and fish samples.

  8. Nanofiltration and granular activated carbon treatment of perfluoroalkyl acids.

    Science.gov (United States)

    Appleman, Timothy D; Dickenson, Eric R V; Bellona, Christopher; Higgins, Christopher P

    2013-09-15

    Perfluoroalkyl acids (PFAAs) are of concern because of their persistence in the environment and the potential toxicological effects on humans exposed to PFAAs through a variety of possible exposure routes, including contaminated drinking water. This study evaluated the efficacy of nanofiltration (NF) and granular activated carbon (GAC) adsorption in removing a suite of PFAAs from water. Virgin flat-sheet NF membranes (NF270, Dow/Filmtec) were tested at permeate fluxes of 17-75 Lm(-2)h(-1) using deionized (DI) water and artificial groundwater. The effects of membrane fouling by humic acid on PFAA rejection were also tested under constant permeate flux conditions. Both virgin and fouled NF270 membranes demonstrated >93% removal for all PFAAs under all conditions tested. GAC efficacy was tested using rapid small-scale columns packed with Calgon Filtrasorb300 (F300) carbon and DI water with and without dissolved organic matter (DOM). DOM effects were also evaluated with F600 and Siemens AquaCarb1240C. The F300 GAC had 20% breakthrough of all PFAAs by 10,000 BVs was observed for all carbons. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. US Domestic Cats as Sentinels for Perfluoroalkyl Substances ...

    Science.gov (United States)

    Perfluoroalkyl substances (PFAS), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) , are persistent, globally distributed, anthropogenic compounds. The primary source(s) for human exposure are not well understood although within home exposure is likely important since many consumer products have been treated with different PFAS, and people spend much of their lives indoors. Herein, domestic cats were used as sentinels to investigate potential exposure and health linkages. PFAS in serum samples of 72 pet and feral cats, including 11 healthy and 61 with one or more primary disease diagnoses, were quantitated using high-resolution time-of-flight mass spectroscopy. All but one sample had detectable PFAS, with PFOS and perfluorohexane sulfonate (PFHxS) ranging from PFAS prevalence and geometric means in cats were very similar to contemporary NHANES reports of human sera in the U. S. POPULATION: The highest PFAS serum concentrations detected were in indoor cats due to disproportionately elevated PFHxS levels. Ranked by quartile, contingency testing indicated that total PFAS levels were positively associated with living indoors and with higher body weight and body condition scores. Individual PFAS quartile rankings suggested positive associations with respiratory effusion, thyroid, liver, and possibly chronic kidney disease . Domestic cats appear to be useful sentinels for assessing primary

  10. Biological and Docking Studies of Sulfonamide Derivatives of 4-Aminophenazone

    International Nuclear Information System (INIS)

    Akhtar, M.S.; Ismail, A.; Murtaza, S.; Shamim, S.; Tahir, M.N.; Usman Ali Rana, U.A.

    2016-01-01

    Sulfonamide derivatives of 4-aminophenazone (4APZ) were synthesized and accordingly characterized by spectroscopic techniques. These newly synthesized compounds were examined for their biological activities such as enzyme inhibition, analgesic, antibacterial, antioxidant and DNA interaction. A direct correlation between enzyme inhibition activity and concentration of the compounds was observed both by experimental and molecular docking studies. Analgesic activity of the compounds was investigated by formalin-induced paw licking (FIPL), acetic acid-induced writhing (AIW) and heat conduction methods in mice. Membrane stabilization effect was determined by hypotonicity-induced hemolysis. Bacterial strains, S. aureus, S. epidermidis, B. subtilis, E. coli, P. aeruginosa, S. mutans and A. odontolyticus were used for investigating the antibacterial potential of the compounds. Antioxidant potential was investigated by Ferric Reducing Antioxidant Power assay (FRAP) and DPPH free radical scavenging method. DNA interaction studies of the synthesized compounds showed weak interaction. Hyperchromic effect was observed along the series and large positive K values were obtained for most of the compounds. (author)

  11. Generic patch inference

    DEFF Research Database (Denmark)

    Andersen, Jesper; Lawall, Julia

    2010-01-01

    A key issue in maintaining Linux device drivers is the need to keep them up to date with respect to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spdiff, that identifies common changes...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

  12. Perfluoroalkyl acid distribution in various plant compartments of edible crops grown in biosolids-amended soils

    Science.gov (United States)

    Crop uptake of perfluoroalkyl acids (PFAAs) from biosolids-amended soil has been identified as a potential pathway for PFAA entry into the terrestrial food chain. This study compared the uptake of PFAAs in greenhouse-grown radish (Raphanus sativus), celery (Apium graveolens var.d...

  13. Perfluoroalkyl and polyfluoralkyl substances (PFASs) in the environment: terminology, classification, and origins

    NARCIS (Netherlands)

    Buck, R.C.; Franklin, J.; Berger, U.; Conder, J.M.; Cousins, I.T.; de Voogt, P.; Jensen, A.A.; Kannan, K.; Mabury, S.A.; van Leeuwen, S.P.J.

    2011-01-01

    The primary aim of this article is to provide an overview of perfluoroalkyl and polyfluoroalkyl substances (PFASs) detected in the environment, wildlife, and humans, and recommend clear, specific, and descriptive terminology, names, and acronyms for PFASs. The overarching objective is to unify and

  14. Perfluoroalkyl and Polyfluoroalkyl Substances in the Enviroment: Terminology, Classification, and Origins

    NARCIS (Netherlands)

    Buck, R.C.; Franklin, J.F.; Berger, U.; Conder, J.M.; Cousins, I.T.; Voogt, de P.; Jensen, A.A.; Kannan, K.; Mabury, S.A.; Leeuwen, van S.P.J.

    2011-01-01

    The primary aim of this article is to provide an overview of perfluoroalkyl and polyfluoroalkyl substances (PFASs) detected in the environment, wildlife, and humans, and recommend clear, specific, and descriptive terminology, names, and acronyms for PFASs. The overarching objective is to unify and

  15. Perfluoroalkyl substances in the Maltese Environment - (I) Surface water and rain water

    NARCIS (Netherlands)

    Sammut, G.; Sinagra, E.; Helmus, R.; de Voogt, P.

    2017-01-01

    The presence of perfluoroalkyl substances (PFASs) in rain water on the Maltese Islands is reported here for the first time and an extensive survey of these substances in surface water also reported. The Maltese archipelago lies at the centre of the Mediterranean Sea and consists of three main

  16. Cooking fish is not effective in reducing exposure to perfluoroalkyl and polyfluoroalkyl substances.

    Science.gov (United States)

    Bhavsar, Satyendra P; Zhang, Xianming; Guo, Rui; Braekevelt, Eric; Petro, Steve; Gandhi, Nilima; Reiner, Eric J; Lee, Holly; Bronson, Roni; Tittlemier, Sheryl A

    2014-05-01

    Consumption of fish is considered a part of a healthy diet; however, health risks from fish consumption exist due to potential exposure to various contaminants accumulated in fish. Cooking fish can reduce exposure to many organic chemicals in fish. Similar results have been presented for low levels of perfluoroalkyl and polyfluoroalkyl substances (PFASs), a class of contaminants of emerging concern, in grocery store fish. We examined the effectiveness of three cooking methods (i.e., baking, broiling, and frying) on reducing PFAS levels in four sport fish species. Samples of Chinook salmon, common carp, lake trout and walleye were collected from four rivers in Ontario, Canada and skin-off fillets were analyzed for regular groups of PFASs such as perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkane sulfonic acids (PFSAs), as well as perfluoroalkyl phosphonic acids (PFPAs), perfluoroalkyl phosphinic acids (PFPIAs) and polyfluoroalkyl phosphoric acid diesters (diPAPs), which are PFASs of emerging concern. Perfluorooctane sulfonate (PFOS) was the dominant PFAS detected and the concentrations were more than an order of magnitude higher than those reported for fish from grocery stores in Canada, Spain, and China. Although concentrations of PFOS in fish fillets generally increase after cooking, amounts of PFOS largely remain unchanged. Relatively minor differences in changes in the fish PFAS amounts after cooking depended on fish species and cooking method used. We conclude that cooking sport fish is generally not an effective approach to reduce dietary exposure to PFASs, especially PFOS. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  17. Persistence of perfluoroalkylated substances in closed bottle tests with municipal sewage sludge

    NARCIS (Netherlands)

    Sáez, M.; de Voogt, P.; Parsons, J.R.

    2008-01-01

    Background, aim, and scope Perfluoroalkylated substances (PFAS) are chemicals with completely fluorinated alkyl chains. The specific properties of the F-C bond give PFAS a high stability and make them very useful in a wide range of applications. PFAS also pose a potential risk to the environment and

  18. Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine

    NARCIS (Netherlands)

    Jørgensen, Kristian T; Specht, Ina O; Lenters, Virissa; Bach, Cathrine C; Rylander, Lars; Jönsson, Bo; Lindh, Christian H; Giwercman, Aleksander; Heederik, Dick; Toft, Gunnar; Bonde, Jens Peter

    2014-01-01

    BACKGROUND: Perfluoroalkyl substances (PFAS) are suggested to affect human fecundity through longer time to pregnancy (TTP). We studied the relationship between four abundant PFAS and TTP in pregnant women from Greenland, Poland and Ukraine representing varying PFAS exposures and pregnancy planning

  19. Perfluoroalkylated substances (PFASs) in home and commercially produced chicken eggs from the Netherlands and Greece

    NARCIS (Netherlands)

    Zafeiraki, Effrosyni; Costopoulou, Danae; Vassiliadou, Irene; Leondiadis, Leondios; Dassenakis, Emmanouil; Hoogenboom, R.L.A.P.; Leeuwen, van S.P.J.

    2016-01-01

    Dietary intake is a major route of human exposure to perfluoroalkylated substances (PFASs). However, the available information on PFAS levels in food, including chicken eggs, is limited. In the present study, home produced and commercially produced eggs (organic, battery and free range eggs) were

  20. Uptake of perfluoroalkyl acids into edible crops via land applied biosolids: Field and greenhouse studies

    Science.gov (United States)

    The presence of perfluoroalkyl acids (PFAAs) in biosolids destined for use in agriculture has raised concerns about their potential to enter the terrestrial food chain via bioaccumulation in edible plants. Uptake of PFAAs by greenhouse lettuce ( Lactuca sativa) and tomato (Lycope...

  1. Stability Indicating HPLC Method for the Determination of Chiral Purity of R-(-)-5-[2-aminopropyl]-2-methoxybenzene Sulfonamide.

    Science.gov (United States)

    Kasawar, G B; Farooqui, M N

    2009-09-01

    A chiral reverse phase liquid chromatographic method was developed for the enantiomeric resolution of racemic mixture of (-)-5-[2-aminopropyl]-2-methoxybenzene sulfonamide in bulk drug. The enantiomeric separation of sulfonamide was resolved on a Crownpak CR (+) column using perchloric acid buffer of pH 1.0 as mobile phase and with UV detection at 226 nm. The method is validated and proved to be robust. The limit of detection and quantification of S (-)-(5)-[2-aminopropyl]-2-methoxybenzene sulfonamide] was found to be 0.084 and 0.159 mug/ml, respectively for 20 mul injection volume. The percentage recovery of S (-)-(5)-[2-aminopropyl]-2-methoxybenzene sulfonamide] ranged from 99.57 to 101.88 in bulk drug samples of R (-)-(5)-[2- aminopropyl]-2-methoxybenzene sulfonamide].

  2. U.S. Domestic Cats as Sentinels for Perfluoroalkyl Substances: Possible Linkages with Housing, Obesity and Disease

    Science.gov (United States)

    Perfluoroalkyl substances (PFAS), such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) , are persistent, globally distributed, anthropogenic compounds. The primary source(s) for human exposure are not well understood although within home exposure is likely i...

  3. Removal and factors influencing removal of sulfonamides and trimethoprim from domestic sewage in constructed wetlands.

    Science.gov (United States)

    Dan A; Yang, Yang; Dai, Yu-Nv; Chen, Chun-Xing; Wang, Su-Yu; Tao, Ran

    2013-10-01

    Twelve pilot-scale constructed wetlands with different configurations were set up in the field to evaluate the removal and factors that influence removal of sulfonamides (sulfadiazine, sulfapyridine, sulfacetamide, sulfamethazine and sulfamethoxazole) and trimethoprim from domestic sewage. The treatments included four flow types, three substrates, two plants and three hydraulic loading rates across two seasons (summer and winter). Most target antibiotics were efficiently removed by specific constructed wetlands; in particular, all types of constructed wetlands performed well for the degradation of sulfapyridine. Flow types were the most important influencing factor in this study, and the best removal of sulfonamides was achieved in vertical subsurface-flow constructed wetlands; however, the opposite phenomenon was found with trimethoprim. Significant relationships were observed between antibiotic degradation and higher temperature and redox potential, which indicated that microbiological pathways were the most probable degradation route for sulfonamides and trimethoprim in constructed wetlands. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Impact of Microbial Growth on Subsurface Perfluoroalkyl Acid Transport

    Science.gov (United States)

    Weathers, T. S.; Higgins, C. P.; Sharp, J.

    2014-12-01

    The fate and transport of poly and perfluoroalkyl substances (PFASs) in the presence of active microbial communities has not been widely investigated. These emerging contaminants are commonly utilized in aqueous film-forming foams (AFFF) and have often been detected in groundwater. This study explores the transport of a suite of perfluorocarboxylic acids and perfluoroalkylsulfonates, including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), in microbially active settings. Single point organic carbon normalized sorption coefficients derived by exposing inactive cellular material to PFASs result in more than an order of magnitude increase in sorption compared to soil organic carbon sorption coefficients found in literature. For example, the sorption coefficients for PFOS are 4.05±0.07 L/kg and 2.80±0.08 L/kg for cellular organic carbon and soil organic carbon respectively. This increase in sorption, coupled with enhanced extracellular polymeric substance production observed during growth of a common hydrocarbon degrading soil microbe exposed to source-level concentrations of PFASs (10 mg/L of 11 analytes, 110 mg/L total) may result in PFAS retardation in situ. To address the upscaling of this phenomenon, flow-through columns packed with low-organic carbon sediment and biostimulated with 10 mg/L glucose were exposed to PFAS concentrations from 15 μg/L to 10 mg/L of each 11 analytes. Breakthrough and tailing of each analyte was measured and modeled with Hydrus-1D to explore sorption coefficients over time for microbially active columns.

  5. Perfluoroalkylated substances (PFAS) affect oxidative stress biomarkers in vitro.

    Science.gov (United States)

    Wielsøe, Maria; Long, Manhai; Ghisari, Mandana; Bonefeld-Jørgensen, Eva C

    2015-06-01

    Perfluoroalkylated substances (PFAS) have been widely used since 1950s and humans are exposed through food, drinking water, consumer products, dust, etc. The long-chained PFAS are persistent in the environment and accumulate in wildlife and humans. They are suspected carcinogens and a potential mode of action is through generation of oxidative stress. Seven long-chained PFAS found in human serum were investigated for the potential to generate reactive oxygen species (ROS), induce DNA damage and disturb the total antioxidant capacity (TAC). The tested PFAS were perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluoroctanoic acid (PFOA), perfluorononanoate (PFNA), perfluorodecanoate (PFDA), perfluoroundecanoate (PFUnA), and perfluorododecanoate (PFDoA). Using the human hepatoma cell line (HepG2) and an exposure time of 24h we found that all three endpoints were affected by one or more of the compounds. PFHxS, PFOA, PFOS and PFNA showed a dose dependent increase in DNA damage in the concentration range from 2×10(-7) to 2×10(-5)M determined by the comet assay. Except for PFDoA, all the other PFAS increased ROS generation significantly. For PFHxS and PFUnA the observed ROS increases were dose-dependent. Cells exposed to PFOA were found to have a significant lower TAC compared with the solvent control, whereas a non-significant trend in TAC decrease was observed for PFOS and PFDoA and an increase tendency for PFHxS, PFNA and PFUnA. Our results indicate a possible genotoxic and cytotoxic potential of the PFAS in human liver cells. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Level and temporal trend of perfluoroalkyl acids in Greenlandic Inuit.

    Science.gov (United States)

    Long, Manhai; Bossi, Rossana; Bonefeld-Jørgensen, Eva C

    2012-03-19

    Perfluoroalkyl acids (PFAAs) have been detected in human blood, breast milk and umbilical cord blood across the globe. PFAAs do accumulate in the marine food chain in Arctic regions. In Greenland, increasing PFAA concentrations were observed during 1982-2006 in ringed seals and polar bears. However, until now, no data have been reported for PFAAs in Greenlandic Inuit. This study assesses the level and temporal trend of serum PFAAs in Greenlandic Inuit. Cross-section and temporal time trend survey. Serum PFAA levels were determined in 284 Inuit from different Greenlandic districts using liquid chromatography-tandem mass spectrometry with electrospray ionization. The temporal time trend of serum PFAAs in Nuuk Inuit during 1998-2005 and the correlation between serum PFAAs and legacy persistent organic pollutants (POPs) were explored. Serum PFAA levels were higher in Nuuk Inuit than in non-Nuuk Inuit. Within the same district, higher PFAA levels were observed for males. An age-dependent, increasing trend of serum PFAA levels in the period from 1998-2005 was observed for Nuuk Inuit. For the pooled gender data, no significant association between PFAAs and legacy POPs was observed for Nuuk Inuit while for non-Nuuk Inuit this correlation was significant. No correlation between PFAAs and legacy POPs was found for male Inuit, whereas significant correlation was observed both for pooled female Inuit and for non-Nuuk Inuit females. We suggest that sources other than seafood intake might contribute to the observed higher PFAA levels in Nuuk Inuit compared to the pooled non-Nuuk Inuit.

  7. Level and temporal trend of perfluoroalkyl acids in Greenlandic Inuit

    Directory of Open Access Journals (Sweden)

    Manhai Long

    2012-03-01

    Full Text Available Objectives: Perfluoroalkyl acids (PFAAs have been detected in human blood, breast milk and umbilical cord blood across the globe. PFAAs do accumulate in the marine food chain in Arctic regions. In Greenland, increasing PFAA concentrations were observed during 1982–2006 in ringed seals and polar bears. However, until now, no data have been reported for PFAAs in Greenlandic Inuit. This study assesses the level and temporal trend of serum PFAAs in Greenlandic Inuit. Study design: Cross-section and temporal time trend survey. Methods: Serum PFAA levels were determined in 284 Inuit from different Greenlandic districts using liquid chromatography-tandem mass spectrometry with electrospray ionization. The temporal time trend of serum PFAAs in Nuuk Inuit during 1998–2005 and the correlation between serum PFAAs and legacy persistent organic pollutants (POPs were explored. Results: Serum PFAA levels were higher in Nuuk Inuit than in non-Nuuk Inuit. Within the same district, higher PFAA levels were observed for males. An age-dependent, increasing trend of serum PFAA levels in the period from 1998–2005 was observed for Nuuk Inuit. For the pooled gender data, no significant association between PFAAs and legacy POPs was observed for Nuuk Inuit while for non-Nuuk Inuit this correlation was significant. No correlation between PFAAs and legacy POPs was found for male Inuit, whereas significant correlation was observed both for pooled female Inuit and for non-Nuuk Inuit females. Conclusions: We suggest that sources other than seafood intake might contribute to the observed higher PFAA levels in Nuuk Inuit compared to the pooled non-Nuuk Inuit.

  8. Identification and dynamic modeling of biomarkers for bacterial uptake and effect of sulfonamide antimicrobials

    International Nuclear Information System (INIS)

    Richter, Merle K.; Focks, Andreas; Siegfried, Barbara; Rentsch, Daniel; Krauss, Martin; Schwarzenbach, René P.; Hollender, Juliane

    2013-01-01

    The effects of sulfathiazole (STA) on Escherichia coli with glucose as a growth substrate was investigated to elucidate the effect-based reaction of sulfonamides in bacteria and to identify biomarkers for bacterial uptake and effect. The predominant metabolite was identified as pterine-sulfathiazole by LC-high resolution mass spectrometry. The formation of pterine-sulfathiazole per cell was constant and independent of the extracellular STA concentrations, as they exceeded the modeled half-saturation concentration K M S of 0.011 μmol L −1 . The concentration of the dihydrofolic acid precursor para-aminobenzoic acid (pABA) increased with growth and with concentrations of the competitor STA. This increase was counteracted for higher STA concentrations by growth inhibition as verified by model simulation of pABA dynamics. The EC value for the inhibition of pABA increase was 6.9 ± 0.7 μmol L −1 STA, which is similar to that calculated from optical density dynamics indicating that pABA is a direct biomarker for the SA effect. - Highlights: ► Elucidation of the effect-based reaction of sulfonamides in bacteria. ► Identification of a biomarker for uptake and effect-based reaction of sulfonamides. ► Investigation of a biomarker for the bacterial growth inhibition by sulfonamides. ► Quantitative mechanistic modeling of biomarker dynamics using enzyme kinetics. ► Mechanistic quantitative linking of sulfonamide concentrations and effects. - Identification of specific biomarkers for the uptake and effect-based reaction of sulfonamides in bacteria and resulting growth inhibition.

  9. Advertising and generic market entry.

    Science.gov (United States)

    Königbauer, Ingrid

    2007-03-01

    The effect of purely persuasive advertising on generic market entry and social welfare is analysed. An incumbent has the possibility to invest in advertising which affects the prescribing physician's perceived relative qualities of the brand-name and the generic version of the drug. Advertising creates product differentiation and can induce generic market entry which is deterred without differentiation due to strong Bertrand competition. However, over-investment in advertising can deter generic market entry under certain conditions and reduces welfare as compared to accommodated market entry.

  10. NET 40 Generics Beginner's Guide

    CERN Document Server

    Mukherjee, Sudipta

    2012-01-01

    This is a concise, practical guide that will help you learn Generics in .NET, with lots of real world and fun-to-build examples and clear explanations. It is packed with screenshots to aid your understanding of the process. This book is aimed at beginners in Generics. It assumes some working knowledge of C# , but it isn't mandatory. The following would get the most use out of the book: Newbie C# developers struggling with Generics. Experienced C++ and Java Programmers who are migrating to C# and looking for an alternative to other generic frameworks like STL and JCF would find this book handy.

  11. Determination of sulfonamides in meat by liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry

    International Nuclear Information System (INIS)

    Kim, Dal Ho; Choi, Jong Oh; Kim, Jin Seog; Lee, Dai Woon

    2002-01-01

    Liquid chromatography/atmospheric pressure chemical ionization-mass spectrometry (LC-APCI-MS) has been used for the determination of sulfonamides in meat. Five typical sulfonamides were selected as target compounds, and beef meat was selected as a matrix sample. As internal standards, sulfapyridine and isotope labeled sulfamethazine ( 13 C 6 -SMZ) were used. Compared to the results of recent reports, our results have shown improved precision to a RSD of 1.8% for the determination of sulfamethazine spiked with 75 ng/g level in meat

  12. Comparison of Generic-to-Brand Switchback Rates Between Generic and Authorized Generic Drugs.

    Science.gov (United States)

    Hansen, Richard A; Qian, Jingjing; Berg, Richard; Linneman, James; Seoane-Vazquez, Enrique; Dutcher, Sarah K; Raofi, Saeid; Page, C David; Peissig, Peggy

    2017-04-01

    Generic drugs contain identical active ingredients as their corresponding brand drugs and are pharmaceutically equivalent and bioequivalent, whereas authorized generic drugs (AGs) contain both identical active and inactive ingredients as their corresponding brand drugs but are marketed as generics. This study compares generic-to-brand switchback rates between generic and AGs. Retrospective cohort study. Claims and electronic health record data from a regional U.S. health care system. The full cohort consisted of 5542 unique patients who received select branded drugs during the 6 months prior to their generic drug market availability (between 1999 and 2014) and then were switched to an AG or generic drug within 30 months of generic drug entry. For these patients, 5929 unique patient-drug combinations (867 with AGs and 5062 with generic drugs) were evaluated. Ten drugs with AGs and generics marketed between 1999 and 2014 were evaluated. The date of the first generic prescription was considered the index date for each drug, and it marked the beginning of follow-up to evaluate the occurrence of generic-to-brand switchback patterns over the subsequent 30 months. Switchback rates were compared between patients receiving AGs versus those receiving generics using multivariable Cox proportional hazards models, controlling for individual drug effects, age, sex, Charlson Comorbidity Score, pre-index drug use characteristics, and pre-index health care utilization. Among the 5542 unique patients who switched from brand to generic or brand to AG, 264 (4.8%) switched back to the brand drug. Overall switchback rates were similar for AGs compared with generics (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.65-1.15). The likelihood of switchback was higher for alendronate (HR 1.64, 95% CI 1.20-2.23) and simvastatin (HR 1.81, 95% CI 1.30-2.54) and lower for amlodipine (HR 0.27, 95% CI 0.17-0.42) compared with the other drugs evaluated. Overall switchback rates were similar

  13. Article choice in plural generics

    NARCIS (Netherlands)

    Farkas, D.F.; Swart, Henriëtte de

    2007-01-01

    We discuss two groups of languages where article use contrasts in generic plural sentences but is otherwise essentially similar. The languages in the first group (English and Dutch) use bare plurals in the expression of kind reference (‘Dinosaurs are extinct’) and in generic

  14. Prenatal Exposure to Perfluoroalkyl Substances and Behavioral Development in Children

    Directory of Open Access Journals (Sweden)

    Ilona Quaak

    2016-05-01

    Full Text Available Background: In recent years, prevalence rates of behavioral disorders in children have increased. One factor possibly implied in the etiology of behavioral disorders is exposure to perfluoroalkyl substances (PFASs. The use of PFASs is highly integrated into everyday life, and exposure is ubiquitous. Exposure to PFASs during early life may be particularly harmful, as it represents a critical time window for brain development. However, research in the area is limited, especially among preschool children. The objective of the current study was to explore the relationship between prenatal exposure to several PFASs and behavioral development at the age of 18 months. Methods: Data from the Dutch cohort LINC (Linking Maternal Nutrition to Child Health were used. Perfluorooctanesulfonic acid (PFOS and perfluorooctanoic acid (PFOA were measured in cord plasma. The total exposure of PFASs was also calculated (ΣPFASs. Behavioral development was assessed with the Child Behavior Checklist 1.5–5 (CBCL 1.5–5. The CBCL scales “Attention Deficit Hyperactivity Disorder” (ADHD and “Externalizing problems” were used for further analysis. Separate regression models were composed for each combination, in which exposure levels were classified in tertiles. Both whole population and sex-stratified analyses were performed. A family history of ADHD, the educational level, smoking or using alcohol or illicit drugs during pregnancy were considered as confounders. In total, data from 76 mother-child pairs was included. Results: No significant associations were found between prenatal PFAS exposure and ADHD scores in the whole population and in the sex-stratified analyses. With regard to externalizing behavior, a significant negative association was found between the highest levels of ΣPFAS exposure and externalizing problem behavior in the whole population, but only in the crude model. After stratifying for sex, boys in the second and third tertile of exposure

  15. Hydroxylamine-O-sulfonamide is a versatile lead compound for the development of carbonic anhydrase inhibitors.

    Science.gov (United States)

    Di Fiore, Anna; Vergara, Alessandro; Caterino, Marco; Alterio, Vincenzo; Monti, Simona M; Ombouma, Joanna; Dumy, Pascal; Vullo, Daniela; Supuran, Claudiu T; Winum, Jean-Yves; De Simone, Giuseppina

    2015-07-21

    Hydroxylamine-O-sulfonamide, a molecule incorporating two zinc-binding groups (ZBGs), has been investigated as a carbonic anhydrase inhibitor (CAI) by means of kinetic, crystallographic and Raman spectroscopy studies, highlighting interesting results on its mechanism of action. These data can be exploited to design new, effective and selective CAIs.

  16. Deciphering the bacterial microbiome in huanglongbing-affected citrus treated with thermotherapy and sulfonamide antibiotics

    Science.gov (United States)

    Huanglongbing (HLB) is a serious citrus disease that threatens the citrus industry. In previous studies, sulfonamide antibiotics and heat treatment suppressed ‘Candidatus Liberibacter asiaticus’ (Las), but did not completely eliminate the Las. Furthermore, there are few reports studying the bacteria...

  17. Multicomponent ternary cocrystals of the sulfonamide group with pyridine-amides and lactams.

    Science.gov (United States)

    Bolla, Geetha; Nangia, Ashwini

    2015-11-04

    SMBA was selected as a bifunctional sulfa drug to design ternary cocrystals with pyridine amides and lactam coformers. Supramolecular assembly of five ternary cocrystals of p-sulfonamide benzoic acid with nicotinamide and 2-pyridone is demonstrated and reproducible heterosynthons are identified for crystal engineering.

  18. Lysine sulfonamides as novel HIV-protease inhibitors: Nepsilon-acyl aromatic alpha-amino acids.

    Science.gov (United States)

    Stranix, Brent R; Lavallée, Jean-François; Sévigny, Guy; Yelle, Jocelyn; Perron, Valérie; LeBerre, Nicholas; Herbart, Dominik; Wu, Jinzi J

    2006-07-01

    A series of lysine sulfonamide analogues bearing Nepsilon-acyl aromatic amino acids were synthesized using an efficient synthetic route. Evaluation of these novel protease inhibitors revealed compounds with high potency against wild-type and multiple-protease inhibitor-resistant HIV viruses.

  19. Preparation and application of epitope magnetic molecularly imprinted polymers for enrichment of sulfonamide antibiotics in water.

    Science.gov (United States)

    Hu, Yufeng; Wang, Cheng; Li, Xiangdao; Liu, Lifen

    2017-10-01

    Sulfonamides, which are widely used synthetic antibiotics, are hydrophilic and stable. They can easily migrate into the environment and aquatic animals, and increase the risk of cancer, drug resistance, and allergic symptoms if consumed by humans. Here, we developed an epitope magnetic imprinting approach to enrich multiple sulfonamide antibiotics from a water sample. Epitope magnetic molecularly imprinted polymers (EMMIPs) were prepared by free-radical polymerization using vinyl-functioned Fe 3 O 4 as a core, sulfanilamide (SA) as a dummy template, methacrylic acid as a functional monomer, and ethylene glycol dimethacrylate as a cross-linker. The performance of the EMMIPs was first evaluated by rebinding SA, and then an adsorption experiment was conducted to assess the extraction of multiple sulfonamide antibiotics containing the SA group. The binding experiments showed that the EMMIPs reached adsorption equilibrium in only 5 min with adsorption of SA at 2040 μg/g, compared with just 462 μg/g for the epitope magnetic non-imprinted polymers. EMMIPs were combined with HPLC for the detection of six sulfonamide antibiotics in surface water samples. The recoveries ranged from 79.3 to 92.4% and the relative standard deviations from 0.9 to 7.3%. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Interaction of nitrogen dioxide with sulfonamide-substituted phthalocyanines: Towards NO2 gas sensor

    Czech Academy of Sciences Publication Activity Database

    Pochekailov, Sergii; Nožár, Juraj; Nešpůrek, Stanislav; Rakušan, J.; Karásková, M.

    2012-01-01

    Roč. 169, 5 July (2012), s. 1-9 ISSN 0925-4005 R&D Projects: GA AV ČR KAN400720701; GA MPO FR-TI1/144 Institutional research plan: CEZ:AV0Z40500505 Keywords : phthalocyanine * sulfonamide * nitrogen dioxide Subject RIV: CG - Electrochemistry Impact factor: 3.535, year: 2012

  1. Synthesis of New Thiazole Derivatives Bearing A Sulfonamide Moiety Of Expected Anticancer And Radiosensitizing Activities

    International Nuclear Information System (INIS)

    Mohamed, S.Sh.I.

    2012-01-01

    In a search for new cytotoxic agents with improved antitumor activity and selectivity, some new pyrano thiazole and thiazolopyranopyrimidine derivatives bearing sulfonamide moiety were synthesized. The newly synthesized compounds were evaluated for their antitumor activity alone and in combination with γ-irradiation. These new compounds were docked inside the active site of carbonic anhydrase II to predict their mechanism of action.

  2. Fate of sulfonamide antibiotics in contact with activated sludge--sorption and biodegradation.

    Science.gov (United States)

    Yang, Sheng-Fu; Lin, Cheng-Fang; Wu, Chien-Ju; Ng, Kok-Kwang; Lin, Angela Yu-Chen; Hong, Pui-Kwan Andy

    2012-03-15

    The sorption and biodegradation of three sulfonamide antibiotics, namely sulfamethoxazole (SMX), sulfadimethoxine (SDM), and sulfamonomethoxine (SMM), in an activated sludge system were investigated. Experiments were carried out by contacting 100 μg/L of each sulfonamide compound individually with 2.56 g/L of MLSS at 25±0.5 °C, pH 7.0, and dissolved oxygen of 3.0±0.1 mg/L in a batch reactor over different periods of 2 d and 14 d. All sulfonamides were removed completely over 11-13 d. Sorptive equilibrium was established well within the first few hours, followed by a lag period of 1-3 days before biodegradation was to deplete the antibiotic compounds linearly in the ensuing 10 days. Apparent zeroth-order rate constants were obtained by regression analysis of measured aqueous concentration vs. time profiles to a kinetic model accounting for sorption and biodegradation; they were 8.1, 7.9, and 7.7 μg/L/d for SDM, SMX, and SMM, respectively, at activated sludge concentration of 2.56 g/L. The measured kinetics implied that with typical hydraulic retention time (e.g. 6 h) provided by WWTP the removal of sulfonamide compounds from the wastewater during the activated sludge process would approximate 2 μg/L. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. Accumulation of sulfonamide resistance genes in arable soils due to repeated application of manure containing sulfadiazine.

    Science.gov (United States)

    Heuer, Holger; Solehati, Qodiah; Zimmerling, Ute; Kleineidam, Kristina; Schloter, Michael; Müller, Tanja; Focks, Andreas; Thiele-Bruhn, Sören; Smalla, Kornelia

    2011-04-01

    Two soils were amended three times with pig manure. The abundance of sulfonamide resistance genes was determined by quantitative PCR 2 months after each application. In both soils treated with sulfadiazine-containing manure, the numbers of copies of sul1 and sul2 significantly increased compared to numbers after treatments with antibiotic-free manure or a control and accumulated with repeated applications.

  4. Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies

    International Nuclear Information System (INIS)

    Zuo, Linzi; Ai, Jing; Fu, Heyun; Chen, Wei; Zheng, Shourong; Xu, Zhaoyi; Zhu, Dongqiang

    2016-01-01

    The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth-KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth-KOH can be attributed to its large specific surface area (2514 m"2/g), high pore volume (1.23 cm"3/g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. - Highlights: • A high efficiency adsorbent for sulfonamide removal is prepared from anthracite. • Effects of

  5. Quality of generic medicines in South Africa

    DEFF Research Database (Denmark)

    Patel, Aarti; Gauld, Robin; Norris, Pauline

    2012-01-01

    Generic Medicines are an important policy option allowing for access to affordable, essential medicines. Quality of generic medicines must be guaranteed through the activities of national medicines regulatory authorities. Existing negative perceptions surrounding the quality of generic medicines ...

  6. Perfluoroalkyl Acid Concentrations in Blood Samples Subjected to Transportation and Processing Delay

    DEFF Research Database (Denmark)

    Bach, Cathrine Carlsen; Henriksen, Tine Brink; Bossi, Rossana

    2015-01-01

    and transportation prior to processing and samples with immediate processing and freezing. METHODS: Pregnant women recruited at Aarhus University Hospital, Denmark, (n = 88) provided paired blood samples. For each pair of samples, one was immediately processed and plasma was frozen, and the other was delayed...... and transported as whole blood before processing and freezing of plasma (similar to the Danish National Birth Cohort). We measured 12 perfluoroalkyl acids and present results for compounds with more than 50% of samples above the lower limit of quantification. RESULTS: For samples taken in the winter, relative...... differences between the paired samples ranged between -77 and +38% for individual perfluoroalkyl acids. In most cases concentrations were lower in the delayed and transported samples, e.g. the relative difference was -29% (95% confidence interval -30; -27) for perfluorooctane sulfonate. For perfluorooctanoate...

  7. Encouraging generic use can yield significant savings.

    Science.gov (United States)

    Zimmerman, Christina

    2012-11-01

    Key findings. (1) Zero copayment for generic drugs is the greatest influencer of generic statin utilization. (2) Both higher copayments for generic drugs and lower copayments for competing brands are associated with a decreased probability of using generic statins. (3) Prior authorization and step therapy requirements for brand-name statins are associated with an increased use of generic drugs. (4) Greater use of generic statins should reduce costs for patients, plans, and Medicare.

  8. Polybrominated Diphenyl Ethers and Perfluoroalkyl Substances in Serum of Pregnant Women

    DEFF Research Database (Denmark)

    Vorkamp, Katrin; Nielsen, Flemming; Kyhl, Henriette Boye

    2014-01-01

    Polybrominated diphenyl ethers (PBDEs), a group of flame retardants, and perfluoroalkyl substances (PFASs) were analysed in serum samples of pregnant women from Denmark to provide information about their exposure and to study indications of common exposure pathways. The main BDE congener was the ...... of exposure and/or pharmacokinetic and metabolisation processes. PBDE and PFAS concentrations were in the range associated with adverse effects in some epidemiological studies....

  9. Evaluation of the efficiency of treatment techniques in removing perfluoroalkyl substances from water

    OpenAIRE

    Lundgren, Sandra

    2014-01-01

    Perfluoroalkylated substances (PFASs) are a group of synthetic compounds that have gained growing attention due to their environmental persistence, toxicity and their potential to bioaccumulate. Even though PFASs are not occurring naturally in our environment, they are globally distributed and can be found ubiquitously in air, water, soil, wildlife as well as in humans. PFASs have primarily been used, due to their unique properties of being both hydrophilic and hydrophobic, as surfactants in ...

  10. Calibration and Application of Passive Sampling in Drinking Water for Perfluoroalkyl Substances

    OpenAIRE

    Persson, Caroline

    2015-01-01

    Perfluoroalkyl substances (PFASs) are global environmental contaminants and a need for monitoring levels has arisen due to their persistency and their ability to bioaccumulate. One relatively novel method of monitoring for both long and short time intervals and generating time-weighted average (TWA) concentrations is passive sampling for which no power, maintenance and supervision is required. The polar organic compound integrative sampler (POCIS) with a weak anion exchange (WAX) sorbent and ...

  11. Tribological reactions of perfluoroalkyl polyether oils with stainless steel under ultrahigh vacuum conditions at room temperature

    Science.gov (United States)

    Mori, Shigeyuki; Morales, Wilfredo

    1989-01-01

    The reaction between three types of commercial perfluoroalkyl polyether (PFPE) oils and stainless steel 440C was investigated experimentally during sliding under ultrahigh vacuum conditions at room temperature. It is found that the tribological reaction of PFPE is mainly affected by the activity of the mechanically formed fresh surfaces of metals rather than the heat generated at the sliding contacts. The fluorides formed on the wear track act as a boundary layer, reducing the friction coefficient.

  12. Persistence of perfluoroalkylated substances in closed bottle tests with municipal sewage sludge

    OpenAIRE

    Sáez, M.; de Voogt, P.; Parsons, J.R.

    2008-01-01

    Background, aim, and scope Perfluoroalkylated substances (PFAS) are chemicals with completely fluorinated alkyl chains. The specific properties of the F-C bond give PFAS a high stability and make them very useful in a wide range of applications. PFAS also pose a potential risk to the environment and humans because they have been recently characterized as persistent, bioaccumulative, and toxic. The objective of this work is to study the bacterial degradation of PFAS under aerobic and anaerobic...

  13. Degradation and Removal Methods for Perfluoroalkyl and Polyfluoroalkyl Substances in Water

    OpenAIRE

    Merino, Nancy; Qu, Yan; Deeb, Rula A.; Hawley, Elisabeth L.; Hoffmann, Michael R.; Mahendra, Shaily

    2016-01-01

    Several perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been identified as chemicals of concern in the environment due to their persistence, global ubiquity, and classification as reproductive and developmental toxicants, endocrine disrupters, and possible carcinogens. Multiple PFASs are often found together in the environment due to product manufacturing methods and abiotic and biotic transformations. Treatment methods are needed to effectively sequester or destroy a variety of PF...

  14. Analysis of the presence of perfluoroalkyl substances in water, sediment and biota of the Jucar River (E Spain). Sources, partitioning and relationships with water physical characteristics

    Energy Technology Data Exchange (ETDEWEB)

    Campo, Julian, E-mail: Julian.Campo@uv.es [Environmental Forensic and Landscape Chemistry Research Group. Desertification Research Centre - CIDE (Spanish Council for Scientific Research, University of Valencia, Generalitat Valenciana), Carretera Moncada - Náquera km 4.5 (Campus IVIA), Moncada, 46113 Valencia (Spain); Earth Surface Science, Institute for Biodiversity and Ecosystems Dynamics, University of Amsterdam, Science Park 904, 1098 XH Amsterdam (Netherlands); Lorenzo, María [Food and Environmental Safety Research Group (SAMA–UV), Centro de Investigaciones sobre Desertificación (CIDE, UV–CSIC–GV) and Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, Burjassot, 46100 Valencia (Spain); Pérez, Francisca [Department of Environmental Chemistry (IDAEA-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); Picó, Yolanda [Food and Environmental Safety Research Group (SAMA–UV), Centro de Investigaciones sobre Desertificación (CIDE, UV–CSIC–GV) and Facultat de Farmàcia, Universitat de València, Av. Vicent Andrés Estellés s/n, Burjassot, 46100 Valencia (Spain); Farré, Marinella [Department of Environmental Chemistry (IDAEA-CSIC), Jordi Girona 18-26, 08034 Barcelona (Spain); and others

    2016-05-15

    The presence, sources and partitioning of 21 perfluoroalkyl substances (PFASs: C4–C14, C16, C18 carboxylate, C4, C6–C10 sulfonates and C8 sulfonamide) were assessed in water, sediment, and biota of the Jucar River basin (E Spain). Considering the three matrices, perfluoropentanoate (PFPeA) and perfluorooctane sulfonate (PFOS) were the most frequent compounds, being remarkable the high occurrence of short-chain PFASs (C≤8), which are intended to replace the long-chain ones in several industrial and commercial applications. In general, all samples were contaminated with at least one PFAS, with the exception of three fish samples. Mean concentrations detected in sediments (0.22–11.5 ng g{sup −1}) and biota (0.63–274 µg kg{sup −1}) samples were higher than those measured in water (0.04–83.1 ng L{sup −1}), which might suggest (bio) accumulation. The occurrence of PFAS is related to urban and industrial discharges (Cuenca city in the upper part of basin, and car's factory, and effluents of the sewage treatment plant (STP) of Alzira, in the lower part). Increasing pollution gradients were found. On the other hand, higher contamination levels were observed after regulation dams of the catchment pointing out their importance in the re-distribution of these contaminants. None of the hazard quotients (HQ) calculated indicate potential risk for the different tropic levels considered (algae, Daphnia sp. and fish). PFAS concentrations found in this study can be considered in acceptable levels if compared to existing Regulatory Legislation and, consequently, they do not pose an immediate human health risk. - Highlights: • Distribution of 21 PFASs in water, sediment, biota of Jucar River is established. • PFPeA and PFOS are the predominant but high PFDA levels are related to industry. • PFASs in water and sediment related to the increase in NaCl, conductivity and TDS. • PFAS concentration in sediment/biota suggests (bio)accumulation. • None of the

  15. Analysis of the presence of perfluoroalkyl substances in water, sediment and biota of the Jucar River (E Spain). Sources, partitioning and relationships with water physical characteristics

    International Nuclear Information System (INIS)

    Campo, Julian; Lorenzo, María; Pérez, Francisca; Picó, Yolanda; Farré, Marinella

    2016-01-01

    The presence, sources and partitioning of 21 perfluoroalkyl substances (PFASs: C4–C14, C16, C18 carboxylate, C4, C6–C10 sulfonates and C8 sulfonamide) were assessed in water, sediment, and biota of the Jucar River basin (E Spain). Considering the three matrices, perfluoropentanoate (PFPeA) and perfluorooctane sulfonate (PFOS) were the most frequent compounds, being remarkable the high occurrence of short-chain PFASs (C≤8), which are intended to replace the long-chain ones in several industrial and commercial applications. In general, all samples were contaminated with at least one PFAS, with the exception of three fish samples. Mean concentrations detected in sediments (0.22–11.5 ng g −1 ) and biota (0.63–274 µg kg −1 ) samples were higher than those measured in water (0.04–83.1 ng L −1 ), which might suggest (bio) accumulation. The occurrence of PFAS is related to urban and industrial discharges (Cuenca city in the upper part of basin, and car's factory, and effluents of the sewage treatment plant (STP) of Alzira, in the lower part). Increasing pollution gradients were found. On the other hand, higher contamination levels were observed after regulation dams of the catchment pointing out their importance in the re-distribution of these contaminants. None of the hazard quotients (HQ) calculated indicate potential risk for the different tropic levels considered (algae, Daphnia sp. and fish). PFAS concentrations found in this study can be considered in acceptable levels if compared to existing Regulatory Legislation and, consequently, they do not pose an immediate human health risk. - Highlights: • Distribution of 21 PFASs in water, sediment, biota of Jucar River is established. • PFPeA and PFOS are the predominant but high PFDA levels are related to industry. • PFASs in water and sediment related to the increase in NaCl, conductivity and TDS. • PFAS concentration in sediment/biota suggests (bio)accumulation. • None of the calculated

  16. Role of Snow Deposition of Perfluoroalkylated Substances at Coastal Livingston Island (Maritime Antarctica).

    Science.gov (United States)

    Casal, Paulo; Zhang, Yifeng; Martin, Jonathan W; Pizarro, Mariana; Jiménez, Begoña; Dachs, Jordi

    2017-08-01

    Perfluoroalkyl substances (PFAS) are ubiquitous in the environment, including remote polar regions. To evaluate the role of snow deposition as an input of PFAS to Maritime Antarctica, fresh snow deposition, surface snow, streams from melted snow, coastal seawater, and plankton samples were collected over a three-month period (December 2014-February 2015) at Livingston Island. Local sources of PFASs were significant for perfluoroalkyl sulfonates (PFSAs) and C7-14 perfluoroalkyl carboxylates (PFCAs) in snow but limited to the transited areas of the research station. The concentrations of 14 ionizable PFAS (∑PFAS) in freshly deposited snow (760-3600 pg L -1 ) were 1 order of magnitude higher than those in background surface snow (82-430 pg L -1 ). ∑PFAS ranged from 94 to 420 pg L -1 in seawater and from 3.1 to 16 ng g dw -1 in plankton. Ratios of individual PFAS concentrations in freshly deposited snow relative to surface snow (C SD /C Snow ), snowmelt (C SD /C SM ), and seawater (C SD /C SW ) were close to 1 (from 0.44 to 1.4) for all perfluorooctanesulfonate (PFOS) isomers, suggesting that snowfall does not contribute significantly to PFOS in seawater. Conversely, these ratios for PFCAs ranged from 1 to 33 and were positively correlated with the number of carbons in the PFCA alkylated chain. These trends suggest that snow deposition, scavenging sea-salt aerosol bound PFAS, plays a role as a significant input of PFCAs to the Maritime Antarctica.

  17. Geochemical and hydrologic factors controlling subsurface transport of poly- and perfluoroalkyl substances, Cape Cod, Massachusetts

    Science.gov (United States)

    Weber, Andrea K.; Barber, Larry B.; LeBlanc, Denis R.; Sunderland, Elsie M.; Vecitis, Chad D.

    2017-01-01

    Growing evidence that certain poly- and perfluoroalkyl substances (PFASs) are associated with negative human health effects prompted the U.S. Environmental Protection Agency to issue lifetime drinking water health advisories for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in 2016. Given that groundwater is a major source of drinking water, the main objective of this work was to investigate geochemical and hydrological processes governing the subsurface transport of PFASs at a former fire training area (FTA) on Cape Cod, Massachusetts, where PFAS-containing aqueous film-forming foams were used historically. A total of 148 groundwater samples and 4 sediment cores were collected along a 1200-m-long downgradient transect originating near the FTA and analyzed for PFAS content. The results indicate that unsaturated zones at the FTA and at hydraulically downgradient former domestic wastewater effluent infiltration beds both act as continuous PFAS sources to the groundwater despite 18 and 20 years of inactivity, respectively. Historically different PFAS sources are evident from contrasting PFAS composition near the water table below the FTA and wastewater-infiltration beds. Results from total oxidizable precursor assays conducted using groundwater samples collected throughout the plume suggest that some perfluoroalkyl acid precursors at this site are transporting with perfluoroalkyl acids.

  18. Distribution of perfluoroalkyl compounds in Osaka Bay and coastal waters of Western Japan.

    Science.gov (United States)

    Beškoski, Vladimir P; Yamamoto, Katsuya; Yamamoto, Atsushi; Okamura, Hideo; Hayashi, Mitsuru; Nakano, Takeshi; Matsumura, Chisato; Fukushi, Keiichi; Wada, Shinpei; Inui, Hideyuki

    2017-03-01

    Perfluoroalkyl acids (PFAAs) including perfluoroalkyl sulfonates (PFSAs) and perfluoroalkyl carboxylates (PFCAs) were analyzed in sediment samples taken from Ajifu Waterway in Osaka city, from Osaka Bay, and from Kagoshima Bay, as well as in fifteen seawater samples collected from Osaka Bay and coastal waters of Western Japan. In all sediment samples, only PFCAs were detected, and the highest concentration was determined in Ajifu Waterway, where ΣPFAA was 58990 ng kg -1 dry weight. The total concentrations of PFAAs in sea water samples ranged between the limit of quantification and 53.4 ng L -1 , and perfluorohexanoic acid was the most prevalent and had the highest concentration of 37 ng L -1 . The changes in the patterns and concentrations of PFAAs in Osaka Bay and coastal waters of Western Japan indicate that the PFAAs in surface waters are influenced by sources from Keihanshin Metropolitan Area, mainly the Yodo River basin, and the dilution effect which naturally occurs during their transport to the Pacific Ocean. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Generic Drugs: Questions and Answers

    Science.gov (United States)

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Drugs Home Drugs Resources for You Information for Consumers (Drugs) Questions & Answers Generic Drugs: Questions & Answers Share Tweet Linkedin Pin it More ...

  20. The Generic Data Capture Facility

    Science.gov (United States)

    Connell, Edward B.; Barnes, William P.; Stallings, William H.

    1987-01-01

    The Generic Data Capture Facility, which can provide data capture support for a variety of different types of spacecraft while enabling operations costs to be carefully controlled, is discussed. The data capture functions, data protection, isolation of users from data acquisition problems, data reconstruction, and quality and accounting are addressed. The TDM and packet data formats utilized by the system are described, and the development of generic facilities is considered.

  1. Hanford Generic Interim Safety Basis

    Energy Technology Data Exchange (ETDEWEB)

    Lavender, J.C.

    1994-09-09

    The purpose of this document is to identify WHC programs and requirements that are an integral part of the authorization basis for nuclear facilities that are generic to all WHC-managed facilities. The purpose of these programs is to implement the DOE Orders, as WHC becomes contractually obligated to implement them. The Hanford Generic ISB focuses on the institutional controls and safety requirements identified in DOE Order 5480.23, Nuclear Safety Analysis Reports.

  2. Hanford Generic Interim Safety Basis

    International Nuclear Information System (INIS)

    Lavender, J.C.

    1994-01-01

    The purpose of this document is to identify WHC programs and requirements that are an integral part of the authorization basis for nuclear facilities that are generic to all WHC-managed facilities. The purpose of these programs is to implement the DOE Orders, as WHC becomes contractually obligated to implement them. The Hanford Generic ISB focuses on the institutional controls and safety requirements identified in DOE Order 5480.23, Nuclear Safety Analysis Reports

  3. Perfluoroalkyl substances in older male anglers in Wisconsin.

    Science.gov (United States)

    Christensen, Krista Y; Raymond, Michelle; Thompson, Brooke A; Anderson, Henry A

    2016-05-01

    Perfluoroalkyl substances (PFAS) are an emerging class of contaminants. Certain PFAS are regulated or voluntarily limited due to concern about environmental persistence and adverse health effects, including thyroid disease and to dyslipidemia. The major source of PFAS exposure in the general population is seafood. In this analysis we examine PFAS levels and their determinants, as well as associations between PFAS levels and self-reported health outcomes, in a group of older male anglers in Wisconsin with high fish consumption. A biomonitoring study of male anglers aged 50 and older living in Wisconsin collected detailed information on fish consumption, demographics and self-reported health outcomes, along with hair and blood samples for biomarker analysis. Sixteen different PFAS were extracted from serum samples. Regression models were used to identify factors (demographic characteristics and fish consumption habits) associated with PFAS biomarker levels in blood, as well as associations between PFAS and self-reported health outcomes, adjusting for potential confounders. Seven PFAS were detected in at least 30% of participants and were used in subsequent analyses (PFDA, PFHpS, PFHxS, PFNA, PFOA, PFOS, PFuDA). The PFAS with the highest levels were PFOS, followed by PFOA, PFHxS and PFNA (medians of 19.0, 2.5, 1.8 and 1.4ng/mL). In general, increasing age was associated with higher PFAS levels, while increasing BMI were associated with lower PFAS levels. Greater alcohol consumption was associated with higher levels of PFHpS, PFHxS and PFOA. Associations with smoking and employment did not show a consistent pattern. Associations between fish consumption and PFAS were generally weak, with the exception of notably higher PFDA and PFHpS with both other locally-caught fish, and restaurant-purchased fish. Regarding associations with health outcomes, PFuDA, PFNA and PFDA were all associated with increased risk of pre-diabetes and/or diabetes. PFHpS was associated with a

  4. Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies.

    Science.gov (United States)

    Zuo, Linzi; Ai, Jing; Fu, Heyun; Chen, Wei; Zheng, Shourong; Xu, Zhaoyi; Zhu, Dongqiang

    2016-04-01

    The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth-KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth-KOH can be attributed to its large specific surface area (2514 m(2)/g), high pore volume (1.23 cm(3)/g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Stability Indicating HPLC Method for the Determination of Chiral Purity of R-(-)-5-[2-aminopropyl]-2-methoxybenzene Sulfonamide

    OpenAIRE

    Kasawar, G. B.; Farooqui, M. N.

    2009-01-01

    A chiral reverse phase liquid chromatographic method was developed for the enantiomeric resolution of racemic mixture of (-)-5-[2-aminopropyl]-2-methoxybenzene sulfonamide in bulk drug. The enantiomeric separation of sulfonamide was resolved on a Crownpak CR (+) column using perchloric acid buffer of pH 1.0 as mobile phase and with UV detection at 226 nm. The method is validated and proved to be robust. The limit of detection and quantification of S (-)-(5)-[2-aminopropyl]-2-methoxyben...

  6. L-Threonine-derived novel bifunctional phosphine-sulfonamide catalyst-promoted enantioselective aza-morita-Baylis-Hillman reaction

    KAUST Repository

    Zhong, Fangrui

    2011-03-18

    A series of novel bifunctional phosphine-sulfonamide organic catalysts were designed and readily prepared from natural amino acids, and they were utilized to promote enantioselective aza-Morita-Baylis-Hillman (MBH) reactions. l-Threonine-derived phosphine-sulfonamide 9b was found to be the most efficient catalyst, affording the desired aza-MBH adducts in high yields and with excellent enantioselectivities. © 2011 American Chemical Society.

  7. Prevalence and characterization of plasmids carrying sulfonamide resistance genes among Escherichia coli from pigs, pig carcasses and human

    OpenAIRE

    Wu, Shuyu; Dalsgaard, Anders; Hammerum, Anette M; Porsbo, Lone J; Jensen, Lars B

    2010-01-01

    Abstract Background Sulfonamide resistance is very common in Escherichia coli. The aim of this study was to characterize plasmids carrying sulfonamide resistance genes (sul1, sul2 and sul3) in E. coli isolated from pigs and humans with a specific objective to assess the genetic diversity of plasmids involved in the mobility of sul genes. Methods A total of 501 E. coli isolates from pig feces, pig carcasses and human stools were tested for their susceptibility to selected antimicrobial. Multip...

  8. Generic Example Proving Criteria for All

    Science.gov (United States)

    Yopp, David; Ely, Rob; Johnson­-Leung, Jennifer

    2015-01-01

    We review literature that discusses generic example proving and highlight ambiguities that pervade our research community's discourse about generic example arguments. We distinguish between pedagogical advice for choosing good examples that can serve as generic examples when teaching and advice for developing generic example arguments. We provide…

  9. Generic penetration in the retail antidepressant market.

    Science.gov (United States)

    Ventimiglia, Jeffrey; Kalali, Amir H

    2010-06-01

    In this article, we explore the accelerated penetration of generic antidepressants in the United States market following the availability of generic citalopram and sertraline. Analysis suggests that overall, generic penetration into the antidepressant market has grown from approximately 41 percent in January 2004 to over 73 percent in January 2010. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

  10. Rationalization of activity cliffs of a sulfonamide inhibitor of DNA methyltransferases with induced-fit docking.

    Science.gov (United States)

    Medina-Franco, José L; Méndez-Lucio, Oscar; Yoo, Jakyung

    2014-02-21

    Inhibitors of human DNA methyltransferases (DNMT) are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure-activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of 'activity cliffs', e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay.

  11. Distribution of quinolones, sulfonamides, tetracyclines in aquatic environment and antibiotic resistance in Indochina

    Directory of Open Access Journals (Sweden)

    Satoru eSuzuki

    2012-02-01

    Full Text Available Southeast Asia has become the center of rapid industrial development and economic growth. However, this growth has far outpaced investment in public infrastructure, leading to the unregulated release of many pollutants, including wastewater-related contaminants such as antibiotics. Antibiotics are of major concern because they can easily be released into the environment from numerous sources, and can subsequently induce development of antibiotic-resistant bacteria. Recent studies have shown that for some categories of drugs this source-to-environment antibiotic resistance relationship is more complex. This review summarizes current understanding regarding the presence of quinolones, sulfonamides, and tetracyclines in aquatic environments of Indochina and the prevalence of bacteria resistant to them. Several noteworthy findings are discussed: 1 quinolone contamination and the occurrence of quinolone resistance are not correlated; 2 occurrence of the sul sulfonamide resistance gene varies geographically; and 3 microbial diversity might be related to the rate of oxytetracycline resistance.

  12. Synthesis and antimalarial activity of new 4-amino-7-chloroquinolyl amides, sulfonamides, ureas and thioureas.

    Science.gov (United States)

    Ekoue-Kovi, Kekeli; Yearick, Kimberly; Iwaniuk, Daniel P; Natarajan, Jayakumar K; Alumasa, John; de Dios, Angel C; Roepe, Paul D; Wolf, Christian

    2009-01-01

    We report the synthesis and in vitro antimalarial activities of more than 50 7-chloro-4-aminoquinolyl-derived sulfonamides 3-8 and 11-26, ureas 19-22, thioureas 23-26, and amides 27-54. Many of the CQ analogues prepared for this study showed submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strains of Plasmodium falciparum) and low resistance indices were obtained in most cases. Systematic variation of the side chain length and introduction of fluorinated aliphatic and aromatic termini revealed promising leads that overcome CQ resistance. In particular, sulfonamide 3 exhibiting a short side chain with a terminal dansyl moiety combined high antiplasmodial potency with a low resistance index and showed IC(50)s of 17.5 and 22.7 nM against HB3 and Dd2 parasites.

  13. Sulfonamide and carbamate derivatives of 6-chloropurine: synthesis, characterization and antimicrobial activity evaluation

    Directory of Open Access Journals (Sweden)

    K. Venkata Narayana

    2016-07-01

    Full Text Available A series of new sulfonamide derivatives, 9-(substitutedbenzenesulfonyl-6-chloro-9H-purines 7(a-e and carbamate derivatives, 6-chloro-purine-9-carboxylic acid substituted alkyl/arylester 9(a-d, have been synthesized through an intermediate, sodium salt of 6-chloro-9(H-purine (6 which was prepared by the treatment of 6-chloro-9(H-purine (4 with sodium hydride. Structures of the newly synthesized compounds were elucidated by IR, NMR ( 1H and 13C, mass spectra and elemental analysis. Antimicrobial activity against three bacterial strains and three fungal strains at two different concentrations, 100 and 200 µg/mL including MIC values was investigated. Bio-screening data disclosed that most of the sulfonamide derivatives, 7a, 7c and 7d, and one carbamate derivative 9a showed promising antimicrobial activity having MIC values in the range of 18.0-25.0 µg/mL.

  14. Rationalization of Activity Cliffs of a Sulfonamide Inhibitor of DNA Methyltransferases with Induced-Fit Docking

    Directory of Open Access Journals (Sweden)

    José L. Medina-Franco

    2014-02-01

    Full Text Available Inhibitors of human DNA methyltransferases (DNMT are of increasing interest to develop novel epi-drugs for the treatment of cancer and other diseases. As the number of compounds with reported DNMT inhibition is increasing, molecular docking is shedding light to elucidate their mechanism of action and further interpret structure–activity relationships. Herein, we present a structure-based rationalization of the activity of SW155246, a distinct sulfonamide compound recently reported as an inhibitor of human DNMT1 obtained from high-throughput screening. We used flexible and induce-fit docking to develop a binding model of SW155246 with a crystallographic structure of human DNMT1. Results were in excellent agreement with experimental information providing a three-dimensional structural interpretation of ‘activity cliffs’, e.g., analogues of SW155246 with a high structural similarity to the sulfonamide compound, but with no activity in the enzymatic assay.

  15. Piperazine sulfonamide BACE1 inhibitors: Design, synthesis, and in vivo characterization

    Energy Technology Data Exchange (ETDEWEB)

    Cumming, Jared; Babu, Suresh; Huang, Ying; Carrol, Carolyn; Chen, Xia; Favreau, Leonard; Greenlee, William; Guo, Tao; Kennedy, Matthew; Kuvelkar, Reshma; Le, Thuy; Li, Guoqing; McHugh, Nansie; Orth, Peter; Ozgur, Lynne; Parker, Eric; Saionz, Kurt; Stamford, Andrew; Strickland, Corey; Tadesse, Dawit; Voigta, Johannes; Zhang, Lili; Zhang, Qi (Ligand); (Merck)

    2010-08-17

    With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2{prime} sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral A{beta}{sub 40} in transgenic mice with a single subcutaneous dose.

  16. Deciphering the Bacterial Microbiome in Huanglongbing-Affected Citrus Treated with Thermotherapy and Sulfonamide Antibiotics.

    Directory of Open Access Journals (Sweden)

    Chuanyu Yang

    Full Text Available Huanglongbing (HLB is a serious citrus disease that threatens the citrus industry. In previous studies, sulfonamide antibiotics and heat treatment suppressed 'Candidatus Liberibacter asiaticus' (Las, but did not completely eliminate the Las. Furthermore, there are few reports studying the bacterial microbiome of HLB-affected citrus treated by heat and sulfonamide antibiotics. In this study, combinations of heat (45°C or 40°C and sulfonamide treatment (sulfathiazole sodium-STZ, or sulfadimethoxine sodium-SDX were applied to HLB-affected citrus. The bacterial microbiome of HLB-affected citrus following thermotherapy and/or chemotherapy was characterized by PhyloChipTMG3-based metagenomics. Our results showed that the combination of thermotherapy at 45°C and chemotherapy with STZ and SDX was more effective against HLB than thermotherapy alone, chemotherapy alone, or a combination of thermotherapy at 40°C and chemotherapy. The PhyloChipTMG3-based results indicated that 311 empirical Operational Taxonomic Units (eOTUs were detected in 26 phyla. Cyanobacteria (18.01% were dominant after thermo-chemotherapy. Thermotherapy at 45°C decreased eOTUs (64.43% in leaf samples, compared with thermotherapy at 40°C (73.96% or without thermotherapy (90.68% and it also reduced bacterial family biodiversity. The eOTU in phylum Proteobacteria was reduced significantly and eOTU_28, representing "Candidatus Liberibacter," was not detected following thermotherapy at 45°C. Following antibiotic treatment with SDX and STZ, there was enhanced abundance of specific eOTUs belonging to the families Streptomycetaceae, Desulfobacteraceae, Chitinophagaceae, and Xanthomonadaceae, which may be implicated in increased resistance to plant pathogens. Our study further develops an integrated strategy for combating HLB, and also provides new insight into the bacterial microbiome of HLB-affected citrus treated by heat and sulfonamide antibiotics.

  17. Synthesis of Morpholine Containing Sulfonamides: Introduction of Morpholine Moiety on Amine Functional Group

    Directory of Open Access Journals (Sweden)

    D. Singh

    2004-01-01

    Full Text Available Sulfonamides have been the center of drug structures as this group is quite stable & well tolerated in human beings. The synthesis of these structures was started in search of new pharmacological active reagents. These compounds are being tested for the desired activity (ICAM-1/LFA-1 Interaction inhibitors as anti-adhesion therapeutic agents, the biological activity & structure activity relationship will be published elsewhere. Synthesis of morpholine moiety from amino group is done by using reagent 2-chloroethanol.

  18. Surface runoff and transport of sulfonamide antibiotics and tracers on manured grassland.

    Science.gov (United States)

    Burkhardt, Michael; Stamm, Christian; Waul, Christopher; Singer, Heinz; Müller, Stephan

    2005-01-01

    Despite their common use in animal production the environmental fate of the veterinary sulfonamide antibiotics after excretion is only poorly understood. We performed irrigation experiments to investigate the transport of these substances with surface runoff on grassland. Liquid manure from pigs treated with sulfadimidine was spiked with sulfadiazine, sulfathiazole, the herbicide atrazine (2-chloro-4-ethylamino-6-isopropylamino-1,3,5-triazine), and the conservative tracer bromide and spread onto eight plots. Four plots received the same amounts of the spiked substances in aqueous solution (controls). Apart from the application matrix we varied the time between application and irrigation. Manure increased the runoff volume up to six times compared with the controls. It seemed that manure enhanced the runoff by sealing the soil surface. On manured plots the relative antibiotic concentrations in runoff were higher than on the controls, reaching an average of 0.3% (sulfadiazine), 0.8% (sulfathiazole), and 1.4% (sulfadimidine) of the input concentrations after a 1-d contact time. The corresponding values on the controls were 0.16% for sulfadiazine and 0.08% for sulfathiazole. After 3 d, the maximum values on the manured plots were even higher, whereas they had fallen below the limit of quantification on the controls. As a consequence, the sulfonamide losses were 10 to 40 times larger on the manured plots. The relative mobility of the sulfonamides on the control plots followed the trend expected from their chromatographic separation but the opposite was found on the manured plots. Hence it is important to consider explicitly the physical and chemical effects of manure when assessing the environmental fate of sulfonamides.

  19. Electrochemically modified carbon fiber bundles as selective sorbent for online solid-phase microextraction of sulfonamides

    International Nuclear Information System (INIS)

    Ling, Xu; Zhang, Wenpeng; Chen, Zilin

    2016-01-01

    The authors show that carbon fiber bundles electrochemically modified with the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) is a viable sorbent for online solid-phase microextraction (SPME) of the sulfonamides (sulfadiazine, sulfadimidine and sulfamethoxazole) prior to their determination by HPLC. The fibers were packed in a tube loop made from polyether ether ketone (PEEK) that was coupled to the HPLC system for online SPME. Preconcentration factors can reach values of up to 300, and the limit of detection (at an S/N ration of 3) can be as low as 0.05 ng⋅mL −1 . The method was applied to the analysis of the sulfonamides in spiked rat plasma with intra-day and inter-day RSDs of <3.33 and <4.57 %, and with recoveries in the range from 91.7 to 97.8 % in spiked plasma. The in-tube SPME was also applied to the determination of the 3 sulfonamides in rat plasma after oral administration (tablet powder) with high sensitivity. In addition to its efficient extraction, the PEEK tube based SPME has chemical and mechanical stability under even harsh conditions. (author)

  20. Effect of pH and soil structure on transport of sulfonamide antibiotics in agricultural soils.

    Science.gov (United States)

    Park, Jong Yol; Huwe, Bernd

    2016-06-01

    We investigated the effect of solution pH and soil structure on transport of sulfonamide antibiotics (sulfamethoxazole, sulfadimethoxine and sulfamethazine) in combination with batch sorption tests and column experiments. Sorption isotherms properly conformed to Freundlich model, and sorption potential of the antibiotics is as follows; sulfadimethoxine > sulfamethoxazole > sulfamethazine. Decreasing pH values led to increased sorption potential of the antibiotics on soil material in pH range of 4.0-8.0. This likely resulted from abundance of neutral and positive-charged sulfonamides species at low pH, which electrostatically bind to sorption sites on soil surface. Due to destruction of macropore channels, lower hydraulic conductivities of mobile zone were estimated in the disturbed soil columns than in the undisturbed soil columns, and eventually led to lower mobility of the antibiotics in disturbed column. The results suggest that knowledge of soil structure and solution condition is required to predict fate and distribution of sulfonamide antibiotics in environmental matrix. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Structural Basis for the Inhibition of Helicobacter pylori α-Carbonic Anhydrase by Sulfonamides.

    Directory of Open Access Journals (Sweden)

    Joyanta K Modak

    Full Text Available Periplasmic α-carbonic anhydrase of Helicobacter pylori (HpαCA, an oncogenic bacterium in the human stomach, is essential for its acclimation to low pH. It catalyses the conversion of carbon dioxide to bicarbonate using Zn(II as the cofactor. In H. pylori, Neisseria spp., Brucella suis and Streptococcus pneumoniae this enzyme is the target for sulfonamide antibacterial agents. We present structural analysis correlated with inhibition data, on the complexes of HpαCA with two pharmacological inhibitors of human carbonic anhydrases, acetazolamide and methazolamide. This analysis reveals that two sulfonamide oxygen atoms of the inhibitors are positioned proximal to the putative location of the oxygens of the CO2 substrate in the Michaelis complex, whilst the zinc-coordinating sulfonamide nitrogen occupies the position of the catalytic water molecule. The structures are consistent with acetazolamide acting as site-directed, nanomolar inhibitors of the enzyme by mimicking its reaction transition state. Additionally, inhibitor binding provides insights into the channel for substrate entry and product exit. This analysis has implications for the structure-based design of inhibitors of bacterial carbonic anhydrases.

  2. Simultaneous occurrence of nitrates and sulfonamide antibiotics in two ground water bodies of Catalonia (Spain)

    Science.gov (United States)

    García-Galán, M. a. Jesús; Garrido, Teresa; Fraile, Josep; Ginebreda, Antoni; Díaz-Cruz, M. Silvia; Barceló, Damià

    2010-03-01

    SummaryIn the present work the occurrence of 19 selected sulfonamides, including one acetylated metabolite, was investigated in ground water samples taken from two ground water bodies in Catalonia (Plana de Vic and La Selva). Both include areas designated as nitrate vulnerable zones, according to Directive 91/676/EEC. A fully automated analytical methodology based on on-line solid-phase extraction-liquid chromatography-tandem mass spectrometry (on-line SPE-LC-MS/MS) was developed for this purpose. The high selectivity and sensitivity achieved (limits of detection between 0.005 and 0.8 ng/L) permitted to demonstrate the ubiquity of these antibiotics in both ground water bodies. Results showed a wide range of concentrations, from 0.01 ng/L up to 3460.57 ng/L. Since sulfonamides are related to livestock veterinary practices, they can be used as a specific indicator of manure contamination. However, the presence of sulfonamides appeared not to be directly related to the concentration of nitrates, as it is reflected on the low correlation coefficients found.

  3. Effects of pig slurry on the sorption of sulfonamide antibiotics in soil.

    Science.gov (United States)

    Thiele-Bruhn, S; Aust, M O

    2004-07-01

    Sorption of p-aminobenzoic acid (pABA) and five sulfonamide antibiotics to loess Chernozem topsoil amended with varied additions of pig slurry was investigated in batch trials. In unfertilized soil, partition coefficients (Kd) of sulfonamides ranged from 0.3 to 2.0. Strong sorption nonlinearity (1/n = 0.5 to 0.8) was best fitted by the Freundlich isotherm (R2 = 0.7 to 1.0) and was indicative for specific sorption mechanisms. Adsorption to pig slurry was much stronger, and nondesorbable portions were increased compared with soil. However, in a mixture of soil and slurry (50:1 w/w), sorption of the antibiotics was significantly decreased at a lower concentration range of pABA and the sulfonamides. This was attributed to competitive adsorption of dissolved organic matter (DOM) constituents from manure. An increase in pig slurry amendment resulted in increased total organic matter, DOM concentration, and ionic strength, but pH decreased. As a result, the nonadsorbed portions of pABA, sulfanilamide, and sulfadiazine (logD(ow) 0.1)--remained nearly constant in the presence of increased manure input. The pH changes caused by manure amendment strongly affected ionisation status of the latter compounds, thus resulting in increased adsorption, which compensated the mobilizing effect of DOM. It is suggested that the effect of manure be considered in test methods to determine the soil retention of pharmaceutical substances.

  4. Retailing policies for generic medicines.

    Science.gov (United States)

    Narciso, Susana

    2005-06-01

    As there is general disagreement about the way generic medicines should be commercialized, two retailing policies are analyzed, taking into account their effects on the welfare of patients, government, pharmacies and physicians. In the first policy scenario, pharmacies are allowed to substitute generic medicines for branded ones, while in the second, substitution is forbidden. In both cases a pharmacies association is allowed to have a share in the production of generic medicines. The model predicts that under some conditions patients may prefer substitution by pharmacies but when doctors' decisions are binding, they are never "excessively bad". However, the policy choice belongs to the government, which prefers to allow for substitution more often than patients would like.

  5. Generic Graph Grammar: A Simple Grammar for Generic Procedural Modelling

    DEFF Research Database (Denmark)

    Christiansen, Asger Nyman; Bærentzen, Jakob Andreas

    2012-01-01

    in a directed cyclic graph. Furthermore, the basic productions are chosen such that Generic Graph Grammar seamlessly combines the capabilities of L-systems to imitate biological growth (to model trees, animals, etc.) and those of split grammars to design structured objects (chairs, houses, etc.). This results...

  6. Polymorphism in R-tamsulosin (an alpha blocker): The unexpected manifestation of a sulfonamide⋯o-diethoxybenzene heterosynthon

    Science.gov (United States)

    Nanubolu, Jagadeesh Babu; Sridhar, Balasubramanian; Ravikumar, Krishnan

    2014-12-01

    A two point Nsbnd H⋯O dimer or an infinite catemer are the most preferred motifs/synthons for sulfonamide structures. Such synthons are known to be so robust that they are only disrupted in the presence of highly activated O acceptors such as pyridine-N-oxide and sulfoxide. We demonstrate in this article that a multi-point synthon offered by much weaker ethoxy O and amine N acceptors can however strongly compete and disrupt the robust sulfonamide homosynthons. This has been illustrated with the synthon analysis in three polymorphic crystal structures of R-tamsulosin, an active drug used in the treatment of Benign Prostatic Hyperplasia (BPH) and its hydrochloride salt. These crystalline solids are characterized by Single crystal X-ray diffraction (SC-XRD), powder X-ray diffraction (PXRD), Fourier Transform Infrared (FT-IR) and Raman spectroscopy. Forms I, II of the free base and hydrochloride salt crystallize in the monoclinic P21, C2, and P21 space groups respectively with two molecules in the asymmetric unit (Z‧ = 2), whereas, form III of freebase crystallize in the orthorhombic P212121 space group with Z‧ = 1. Remarkably, all four crystal structures contain a totally unexpected sulfonamide⋯o-diethoxybenzene heterosynthon. The multi-point motifs observed in polymorphs are relatively stronger than those in the hydrochloride salt because of the gauche conformation of the tamsulosin linker chain which renders an additional hydrogen bond interaction with amine N acceptor, and resemble the crown ether sulfonamide recognition pattern. Observation of this new heterosynthon offers potential scope in the design of pharmaceutical cocrystals for sulfonamide bearing drug molecules. The present study also presents a detailed hydrogen bond motif analysis in 310 primary sulfonamide structures culled from the latest version of Cambridge Structural Database (CSD). The role of various competing groups is discussed in the context of understanding the most recurring

  7. Generic Software Architecture for Launchers

    Science.gov (United States)

    Carre, Emilien; Gast, Philippe; Hiron, Emmanuel; Leblanc, Alain; Lesens, David; Mescam, Emmanuelle; Moro, Pierre

    2015-09-01

    The definition and reuse of generic software architecture for launchers is not so usual for several reasons: the number of European launcher families is very small (Ariane 5 and Vega for these last decades); the real time constraints (reactivity and determinism needs) are very hard; low levels of versatility are required (implying often an ad hoc development of the launcher mission). In comparison, satellites are often built on a generic platform made up of reusable hardware building blocks (processors, star-trackers, gyroscopes, etc.) and reusable software building blocks (middleware, TM/TC, On Board Control Procedure, etc.). If some of these reasons are still valid (e.g. the limited number of development), the increase of the available CPU power makes today an approach based on a generic time triggered middleware (ensuring the full determinism of the system) and a centralised mission and vehicle management (offering more flexibility in the design and facilitating the long term maintenance) achievable. This paper presents an example of generic software architecture which could be envisaged for future launchers, based on the previously described principles and supported by model driven engineering and automatic code generation.

  8. Testing properties of generic functions

    NARCIS (Netherlands)

    Jansson, P.; Jeuring, J.T.; Cabenda, L.; Engels, G.; Kleerekoper, J.; Mak, S.; Overeem, M.; Visser, Kees

    2007-01-01

    A datatype-generic function is a family of functions indexed by (the structure of) a type. Examples include equality tests, maps and pretty printers. Property based testing tools like QuickCheck and Gast support the de¯nition of properties and test-data generators, and they check if a

  9. Generic component failure data base

    International Nuclear Information System (INIS)

    Eide, S.A.; Calley, M.B.

    1992-01-01

    This report discusses comprehensive component generic failure data base which has been developed for light water reactor probabilistic risk assessments. The Nuclear Computerized Library for Assessing Reactor Reliability (NUCLARR) was used to generate component failure rates. Using this approach, most of the failure rates are based on actual plant data rather then existing estimates

  10. 'Genericism' in Danish welfare professions

    DEFF Research Database (Denmark)

    Larsen, Verner

    and skills in the basic disciplines of the professions also termed as disciplinary and procedural knowledge '. Thus the main research question for this paper is: What consequences do recent reform actions in Danish welfare education concerning generic competence have on developing professional knowledge...

  11. Synthesis of the diazonium (perfluoroalkyl) benzenesulfonimide monomer from Nafion monomer for proton exchange membrane fuel cells

    Science.gov (United States)

    Mei, Hua; D'Andrea, Dan; Nguyen, Tuyet-Trinh; Nworie, Chima

    2014-02-01

    One diazonium (perfluoroalkyl) benzenesulfonimide monomer, perfluoro-3, 6-dioxa-4-methyl-7-octene benzenesulfonyl imide, has been synthesized from Nafion monomer for the first time. With trifluorovinyl ether and diazonium precursors, the partially-fluorinated diazonium PFSI monomer can be polymerized and will provide chemically bonding with carbon electrode in proton exchange membrane fuel cells. A systematic study of the synthesis and characterization of this diazonium PFSI monomer has been conducted by varying reaction conditions. The optimized synthesis method has been established in the lab.

  12. Prenatal Exposure to Perfluoroalkyl Substances and the Risk of Congenital Cerebral Palsy in Children

    DEFF Research Database (Denmark)

    Liew, Zeyan; Ritz, Beate; Bonefeld-Jørgensen, Eva Cecilie

    2014-01-01

    Perfluoroalkyl substances (PFASs) are persistent pollutants and endocrine disruptors that may affect fetal brain development. We investigated whether prenatal exposure to PFASs increases the risk of congenital cerebral palsy (CP). The source population for this study includes 83,389 liveborn...... singletons and mothers enrolled in the Danish National Birth Cohort during 1996-2002. We identified 156 CP cases by linking the cohort to the Danish National Cerebral Palsy Register, and we randomly selected 550 controls using a case-cohort design. We measured 16 PFASs in maternal plasma collected in early...

  13. Application of thermodynamic models to study micellar properties of sodium perfluoroalkyl carboxylates in aqueous solutions

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalez-Perez, Alfredo [Group of Biophysics and Interfaces, Department of Applied Physics, Faculty of Physics, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain)], E-mail: alf@usc.es; Ruso, Juan M. [Group of Biophysics and Interfaces, Department of Applied Physics, Faculty of Physics, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Romero, Maria J. [Department of Inorganic Chemistry, Faculty of Chemistry, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Blanco, Elena [Group of Biophysics and Interfaces, Department of Applied Physics, Faculty of Physics, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Prieto, Gerardo [Group of Biophysics and Interfaces, Department of Applied Physics, Faculty of Physics, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain); Sarmiento, Felix [Group of Biophysics and Interfaces, Department of Applied Physics, Faculty of Physics, University of Santiago de Compostela, E-15782 Santiago de Compostela (Spain)

    2005-06-27

    Sodium perfluoroalkyl carboxylates (CnFONa) with n = 6, 9, 10 have been studied by conductivity measurements at different temperatures. The Krafft point was determined for C9FONa and C10FONa at the highest concentration studied by measuring the temperature dependence of the specific conductivity. The critical micelle concentration (cmc) and the ionization degree of the micelle ({beta}) were estimated from conductivity vs. molality plots at different temperatures. Using these data and previous results on temperature dependence of cmc and {beta} of sodium perfluoroheptanoate and perfluorooctanoate, different models were applied to obtain the thermodynamic properties of micellization. The results are discussed in terms of alkyl chain length.

  14. Application of thermodynamic models to study micellar properties of sodium perfluoroalkyl carboxylates in aqueous solutions

    International Nuclear Information System (INIS)

    Gonzalez-Perez, Alfredo; Ruso, Juan M.; Romero, Maria J.; Blanco, Elena; Prieto, Gerardo; Sarmiento, Felix

    2005-01-01

    Sodium perfluoroalkyl carboxylates (CnFONa) with n = 6, 9, 10 have been studied by conductivity measurements at different temperatures. The Krafft point was determined for C9FONa and C10FONa at the highest concentration studied by measuring the temperature dependence of the specific conductivity. The critical micelle concentration (cmc) and the ionization degree of the micelle (β) were estimated from conductivity vs. molality plots at different temperatures. Using these data and previous results on temperature dependence of cmc and β of sodium perfluoroheptanoate and perfluorooctanoate, different models were applied to obtain the thermodynamic properties of micellization. The results are discussed in terms of alkyl chain length

  15. [Occurrence of quinolone and sulfonamide antibiotics in swine and cattle manures from large-scale feeding operations of Guangdong Province].

    Science.gov (United States)

    Tai, Yi-Ping; Luo, Xiao-Dong; Mo, Ce-Hui; Li, Yan-Wen; Wu, Xiao-Lian; Liu, Xing-Yue

    2011-04-01

    The occurrence and distribution of four quinolones and four sulfonamides in swine and cattle feces sampled from twenty large-scale feeding operations in different areas of Guangdong province were detected using solid phase extraction (SPE) and high performance liquid chromatography (HPLC). Quinolone and sulfonamide compounds were observed in all pig dung samples. Their total concentrations ranged from 24.5 microg/kg to 1516.2 microg/kg (F. W.) with an average of 581.0 microg/kg and ranged from 1925.9-13399.5 microg/kg with an average of 4403.9 microg/kg respectively. The dominant compounds in pig feces were ciprofloxacin and enrofloxacin for quinolones and sulfamerazine and sulfamethoxazole for sulfonamides. Quinolone compounds which dominated with norfloxacin and ciprofloxacin were also observed in all cattle dung samples, its total concentrations ranged from 73.2 microg/kg to 1328.0 microg/kg which averaged 572.9 microg/kg. While the positive rates of sulfonamide compounds detected in cattle dung samples were above 90%, predominated by sulfamethoxazole and sulfamerazine. Concentration and distribution of both quinolone and sulfonamide compounds in swine and cattle dungs of different feeding operations varied greatly. Relatively high concentrations of the two kinds of antibiotics were found in both swine and cattle dungs from Guangzhou area, while sulfameter and sulfamethazine in cattle dungs from Foshan and Shenzhen areas were below the limit of detection.

  16. Shifting Global Exposures to Poly- and Perfluoroalkyl Substances (PFASs) Evident in Longitudinal Birth Cohorts from a Seafood-Consuming Population

    DEFF Research Database (Denmark)

    Dassuncao, Clifton; Hu, Xindi C; Nielsen, Flemming

    2018-01-01

    Rapid declines in legacy poly- and perfluoroalkyl substances (PFASs) have been reported in human populations globally following changes in production since 2000. However, changes in exposure sources are not well understood. Here, we report serum concentrations of 19 PFASs (∑19PFAS) measured in ch...

  17. Perfluoroalkyl substances in polar bear mother-cub pairs: A comparative study based on plasma levels from 1998 and 2008

    NARCIS (Netherlands)

    Bytingsvik, J.; Leeuwen, S.; Hamers, T.; Swart, C.P.; Aars, J.; Lie, E.; Espseth Nilsen, E.M.; Wiig, O.; Derocher, A. E.; Jenssen, B.M.

    2012-01-01

    Perfluoroalkyl substances (PFASs) are protein-binding blood-accumulating contaminants that may have detrimental toxicological effects on the early phases of mammalian development. To enable an evaluation of the potential health risks of PFAS exposure for polar bears (Ursus maritimus), an exposure

  18. Occurrence of perfluoroalkyl substances (PFASs) in various food items of animal origin collected in four European countries

    NARCIS (Netherlands)

    Hlouskova, V; Hradkova, P; Poustka, J; Brambilla, G.; De Filippis, S.P.; D'Hollander, W.; Bervoets, L.; Herzke, D.; Huber, S.; de Voogt, P.; Pulkrabova, J.

    2013-01-01

    This study summarises the results of the levels of 21 perfluoroalkyl substances (PFASs) in 50 selected pooled samples representing 15 food commodities with the special focus on those of animal origin, as meat, seafood, fish, milk, dairy products and hen eggs, which are commonly consumed in various

  19. Estimating human exposure to perfluoroalkyl acids via solid food and drinks : Implementation and comparison of different dietary assessment methods

    NARCIS (Netherlands)

    Papadopoulou, Eleni; Poothong, Somrutai; Koekkoek, Jacco; Lucattini, Luisa; Padilla-Sánchez, Juan Antonio; Haugen, Margaretha; Herzke, Dorte; Valdersnes, Stig; Maage, Amund; Cousins, Ian T.; Leonards, Pim E.G.; Småstuen Haug, Line

    2017-01-01

    Background Diet is a major source of human exposure to hazardous environmental chemicals, including many perfluoroalkyl acids (PFAAs). Several assessment methods of dietary exposure to PFAAs have been used previously, but there is a lack of comparisons between methods. Aim To assess human exposure

  20. Exposure to Perfluoroalkyl Substances and Metabolic Outcomes in Pregnant Women: Evidence from the Spanish INMA Birth Cohorts

    NARCIS (Netherlands)

    Matilla-Santander, N. (Nuria); D. Valvi (Damaskini); M.-J. Lopez-Espinosa (Maria-Jose); Manzano-Salgado, C.B. (Cyntia B.); F. Ballester (Ferran); J. Ibarluzea (Jesús); L. Santa-Marina (Loreto); T. Schettgen (Thomas); M. Guxens Junyent (Mònica); J. Sunyer (Jordi); M. Vrijheid (Martine)

    2017-01-01

    textabstractBACKGROUND: Exposure to perfluoroalkyl substances (PFASs) may increase risk for metabolic diseases; however, epidemiologic evidence is lacking at the present time. Pregnancy is a period of enhanced tissue plasticity for the fetus and the mother and may be a critical window of PFAS

  1. Perfluoroalkylated substances in edible livers of farm animals, including depuration behaviour in young sheep fed with contaminated grass

    NARCIS (Netherlands)

    Zafeiraki, Effrosyni; Vassiliadou, Irene; Costopoulou, Danae; Leondiadis, Leondios; Schafft, Helmut A.; Hoogenboom, Ron L.A.P.; Leeuwen, van Stefan P.J.

    2016-01-01

    Perfluoroalkylated substances (PFASs) present a potential health risk for consumers. In animals these compounds are known to accumulate in livers. In order to determine potential PFASs contamination in commercially available livers, samples from farmed sheep, horses, cows, pigs and chicken were

  2. Determining a Robust D-Optimal Design for Testing for Departure from Additivity in a Mixture of Four Perfluoroalkyl Acids.

    Science.gov (United States)

    Our objective is to determine an optimal experimental design for a mixture of perfluoroalkyl acids (PFAAs) that is robust to the assumption of additivity. PFAAs are widely used in consumer products and industrial applications. The presence and persistence of PFAAs, especially in ...

  3. Longitudinal Associations of Exposure to Perfluoroalkylated Substances in Childhood and Adolescence and Indicators of Adiposity and Glucose Metabolism 6 and 12 Years Later

    DEFF Research Database (Denmark)

    Domazet, Sidsel Louise; Grøntved, Anders; Timmermann, Clara Amalie Gade

    2016-01-01

    OBJECTIVE: To investigate the long-term association of exposure to perfluoroalkylated substances, including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), during childhood (9 years) and adolescence (15 years) on indicators of adiposity and glucose metabolism in adolescence...

  4. Perfluoroalkyl sulfonates cause alkyl chain length-dependent hepatic steatosis and hypolipidemia mainly by impairing lipoprotein production in APOE*3-leiden CETP mice

    NARCIS (Netherlands)

    Bijland, S.; Rensen, P.C.N.; Pieterman, E.J.; Maas, A.C.E.; Hoorn, J.W. van der; Erk, M.J. van; Havekes, L.M.; Dijk, K.W. van; Chang, S.C.; Ehresman, D.J.; Butenhoff, J.L.; Princen, H.M.G.

    2011-01-01

    Perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) are stable perfluoroalkyl sulfonate (PFAS) surfactants, and PFHxS and PFOS are frequently detected in human biomonitoring studies. Some epidemiological studies have shown modest positive

  5. Selected physicochemical aspects of poly- and perfluoroalkylated substances relevant to performance, environment and sustainability-part one.

    Science.gov (United States)

    Krafft, Marie Pierre; Riess, Jean G

    2015-06-01

    The elemental characteristics of the fluorine atom tell us that replacing an alkyl chain by a perfluoroalkyl or polyfluorinated chain in a molecule or polymer is consequential. A brief reminder about perfluoroalkyl chains, fluorocarbons and fluorosurfactants is provided. The outstanding, otherwise unattainable physicochemical properties and combinations thereof of poly and perfluoroalkyl substances (PFASs) are outlined, including extreme hydrophobic and lipophobic character; thermal and chemical stability in extreme conditions; remarkable aptitude to self-assemble into sturdy thin repellent protecting films; unique spreading, dispersing, emulsifying, anti-adhesive and levelling, dielectric, piezoelectric and optical properties, leading to numerous industrial and technical uses and consumer products. It was eventually discovered, however, that PFASs with seven or more carbon-long perfluoroalkyl chains had disseminated in air, water, soil and biota worldwide, are persistent in the environment and bioaccumulative in animals and humans, raising serious health and environmental concerns. Further use of long-chain PFASs is environmentally not sustainable. Most leading manufacturers have turned to shorter four to six carbon perfluoroalkyl chain products that are not considered bioaccumulative. However, many of the key performances of PFASs decrease sharply when fluorinated chains become shorter. Fluorosurfactants become less effective and less efficient, provide lesser barrier film stability, etc. On the other hand, they remain as persistent in the environment as their longer chain homologues. Surprisingly little data (with considerable discrepancies) is accessible on the physicochemical properties of the PFASs under examination, a situation that requires consideration and rectification. Such data are needed for understanding the environmental and in vivo behaviour of PFASs. They should help determine which, for which uses, and to what extent, PFASs are environmentally

  6. Exploring knowledge, perceptions and attitudes about generic ...

    African Journals Online (AJOL)

    Exploring knowledge, perceptions and attitudes about generic medicines among final-year health science students. ... had knowledge deficits about the safety, quality and efficacy of generic medicines. The dissemination of information about generic medicines may strengthen future knowledge, attitudes and perceptions.

  7. Comparing approaches to generic programming in Haskell

    NARCIS (Netherlands)

    Hinze, R.; Jeuring, J.T.; Löh, A.

    2006-01-01

    The last decade has seen a number of approaches to generic programming: PolyP, Functorial ML, `Scrap Your Boilerplate', Generic Haskell, `Generics for the Masses', etc. The approaches vary in sophistication and target audience: some propose full-blown pro- gramming languages, some suggest

  8. Comparing approaches to generic programming in Haskell

    NARCIS (Netherlands)

    Hinze, R.; Jeuring, J.T.; Löh, A.

    2006-01-01

    The last decade has seen a number of approaches to data- type-generic programming: PolyP, Functorial ML, `Scrap Your Boiler- plate', Generic Haskell, `Generics for the Masses', etc. The approaches vary in sophistication and target audience: some propose full-blown pro- gramming languages, some

  9. Proceedings Workshop on Generic Programming (WGP2000)

    NARCIS (Netherlands)

    Jeuring, J.T.

    2000-01-01

    This report contains the papers selected for presentation at the 2nd Workshop on Generic Programming (WGP2000), which was held on July 6, 2000 in Ponte de Lima, Portugal. Generic programming is about making programs more adaptable by making them more general. Generic programs often embody

  10. Vibrational Spectra And Potential Energy Distributions of Normal Modes of N,N'-Etilenbis(P-Toluen sulfonamide)

    International Nuclear Information System (INIS)

    Alyar, S.

    2008-01-01

    N-substituted sulfonamides are well known for their diuretic, antidiabetic, antibacterial and antifungal, anticancer e.g., and are widely used in the therapy of patients. These important bioactive properties are strongly affected by the special features of -CH 2 -SO 2 -NR-linker and intramolecular motion Thus, the studies of energetic and spatial properties on N-substituted sulfonamides are of great importance to improve our understanding of their biological activities and enhance abilities to predict new drugs. Density Functional Theory B3LYP /6-31G(d,p) level has been applied to obtain the vibrational force field for the most stable conformation of N,N'-etilenbis(p-toluensulfonamit)(ptsen)having sulfonamide moiety. The results of these calculation have been compared with spectroscopic data to verify accuracy of calculation and applicability of the DFT approach to ptsen. Additionally, complete normal coordinate analyses with quantum mechanical scaling (SQM) were performed to derive the potential energy distributions (PE)

  11. Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene.

    Science.gov (United States)

    Berryman, Orion B; Johnson, Charles A; Vonnegut, Chris L; Fajardo, Kevin A; Zakharov, Lev N; Johnson, Darren W; Haley, Michael M

    2015-03-04

    Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)-C(sp 2 ) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2'-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N-H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF 4 - or HSO 4 - , where the sulfonamide arms rotate to the side opposite the pyridine N atom.

  12. Solid-State Examination of Conformationally Diverse Sulfonamide Receptors Based on Bis(2-anilinoethynyl)pyridine, -Bipyridine, and -Thiophene

    Science.gov (United States)

    Berryman, Orion B.; Johnson, Charles A.; Vonnegut, Chris L.; Fajardo, Kevin A.; Zakharov, Lev N.; Johnson, Darren W.; Haley, Michael M.

    2015-01-01

    Utilizing an induced-fit model and taking advantage of rotatable acetylenic C(sp)–C(sp2) bonds, we disclose the synthesis and solid-state structures of a series of conformationally diverse bis-sulfonamide arylethynyl receptors using either pyridine, 2,2′-bipyridine, or thiophene as the core aryl group. Whereas the bipyridine and thiophene structures do not appear to bind guests in the solid state, the pyridine receptors form 2 + 2 dimers with water molecules, two halides, or one of each, depending on the protonation state of the pyridine nitrogen atom. Isolation of a related bis-sulfonimide derivative demonstrates the importance of the sulfonamide N–H hydrogen bonds in dimer formation. The pyridine receptors form monomeric structures with larger guests such as BF4− or HSO4−, where the sulfonamide arms rotate to the side opposite the pyridine N atom. PMID:26405435

  13. Inhibition effects of perfluoroalkyl acids on progesterone production in mLTC-1.

    Science.gov (United States)

    Zhao, Wei; Cui, Ruina; Wang, Jianshe; Dai, Jiayin

    2017-06-01

    Perfluoroalkyl substances (PFASs) are a class of fluorine substituted carboxylic acid, sulfonic acid and alcohol, structurally similar to their corresponding parent compounds. Previous study demonstrated the potential endocrine disruption and reproductive toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid, two dominant PFASs in animals and humans. We explored the relationship between eleven perfluoroalkyl acids (PFAAs) with different carbon chain length and their ability to inhibit progesterone production in mouse Leydig tumor cells (mLTC-1). We found an obvious dose-response relationship between progesterone inhibition rate and PFAA exposure concentration in mLTC-1. The relative inhibition rate of progesterone by PFAAs was linearly related to the carbon chain length and molar refractivity of PFAAs. Mitochondrial membrane potential (MMP) decreased after PFAA exposure at the half-maximal inhibitory effect concentration (IC 50 ) of progesterone production in mLTC-1, while the reactive oxygen species (ROS) content increased significantly. These results imply that the inhibition effect of PFAAs on progesterone production might be due, in part, to ROS damage and the decrease in MMP in mLTC-1. Copyright © 2016. Published by Elsevier B.V.

  14. The precautionary principle and chemicals management: The example of perfluoroalkyl acids in groundwater.

    Science.gov (United States)

    Cousins, Ian T; Vestergren, Robin; Wang, Zhanyun; Scheringer, Martin; McLachlan, Michael S

    2016-09-01

    Already in the late 1990s microgram-per-liter levels of perfluorooctane sulfonate (PFOS) were measured in water samples from areas where fire-fighting foams were used or spilled. Despite these early warnings, the problems of groundwater, and thus drinking water, contaminated with perfluoroalkyl and polyfluoroalkyl substances (PFASs) including PFOS are only beginning to be addressed. It is clear that this PFAS contamination is poorly reversible and that the societal costs of clean-up will be high. This inability to reverse exposure in a reasonable timeframe is a major motivation for application of the precautionary principle in chemicals management. We conclude that exposure can be poorly reversible; 1) due to slow elimination kinetics in organisms, or 2) due to poorly reversible environmental contamination that leads to continuous exposure. In the second case, which is relevant for contaminated groundwater, the reversibility of exposure is not related to the magnitude of a chemical's bioaccumulation potential. We argue therefore that all PFASs entering groundwater, irrespective of their perfluoroalkyl chain length and bioaccumulation potential, will result in poorly reversible exposures and risks as well as further clean-up costs for society. To protect groundwater resources for future generations, society should consider a precautionary approach to chemicals management and prevent the use and release of highly persistent and mobile chemicals such as PFASs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Age- and gender-related accumulation of perfluoroalkyl substances in captive Chinese alligators (Alligator sinensis)

    International Nuclear Information System (INIS)

    Wang, Jianshe; Zhang, Yating; Zhang, Fang; Yeung, Leo W.Y.; Taniyasu, Sachi; Yamazaki, Eriko; Wang, Renping; Lam, Paul K.S.; Yamashita, Nobuyoshi; Dai, Jiayin

    2013-01-01

    Fourteen perfluoroalkyl substances (PFASs) were measured in serum of the highly endangered captive Chinese alligators, whole body homogenates of six kinds of fish (alligator prey species), and pond water (alligator habitat) in the Anhui Research Center for Chinese Alligator Reproduction. Six PFASs, including PFOS and five perfluorinated carboxylates, were detected in all alligator samples. The most dominant PFAS was PFUnDA, with a mean value of 31.4 ng/mL. Significant positive correlations were observed among the six PFASs, suggesting that they shared similar sources of contamination. Significantly higher PFOS and PFUnDA levels were observed in males, but the other four PFCAs did not differ between genders. An age related PFAS bioaccumulation analysis showed a significant negative correlation of the concentrations for five PFCAs to age, which means that higher concentrations were found in younger animals. Bioaccumulation factors (BAF) in fish for PFASs ranged from 21 to 28,000, with lower BAF for PFOA than that for longer carbon chain PFCAs, including PFUnDA, PFDA, and PFNA. Highlights: •The most dominant PFAS was PFUnDA, followed by PFOS and PFDA in all alligator samples. •Significantly higher PFOS and PFUnDA levels were observed in males. •The concentrations of the five PFCAs showed significant negative correlation to age. -- Age- and gender-related accumulation of perfluoroalkyl substances in captive Chinese alligators

  16. High Performance Nanofiltration Membrane for Effective Removal of Perfluoroalkyl Substances at High Water Recovery.

    Science.gov (United States)

    Boo, Chanhee; Wang, Yunkun; Zucker, Ines; Choo, Youngwoo; Osuji, Chinedum O; Elimelech, Menachem

    2018-05-31

    We demonstrate the fabrication of a loose, negatively charged nanofiltration (NF) membrane with tailored selectivity for the removal of perfluoroalkyl substances with reduced scaling potential. A selective polyamide layer was fabricated on top of a polyethersulfone support via interfacial polymerization of trimesoyl chloride and a mixture of piperazine and bipiperidine. Incorporating high molecular weight bipiperidine during the interfacial polymerization enables the formation of a loose, nanoporous selective layer structure. The fabricated NF membrane possessed a negative surface charge and had a pore diameter of ~1.2 nm, much larger than a widely used commercial NF membrane (i.e., NF270 with pore diameter of ~0.8 nm). We evaluated the performance of the fabricated NF membrane for the rejection of different salts (i.e., NaCl, CaCl2, and Na2SO4) and perfluorooctanoic acid (PFOA). The fabricated NF membrane exhibited a high retention of PFOA (~90%) while allowing high passage of scale-forming cations (i.e., calcium). We further performed gypsum scaling experiments to demonstrate lower scaling potential of the fabricated loose porous NF membrane compared to NF membranes having a dense selective layer under solution conditions simulating high water recovery. Our results demonstrate that properly designed NF membranes are a critical component of a high recovery NF system, which provide an efficient and sustainable solution for remediation of groundwater contaminated with perfluoroalkyl substances.

  17. Perfluoroalkyl acids (PFAAs) in the Pra and Kakum River basins and associated tap water in Ghana.

    Science.gov (United States)

    Essumang, David K; Eshun, Albert; Hogarh, Jonathan N; Bentum, John K; Adjei, Joseph K; Negishi, Junya; Nakamichi, Shihori; Habibullah-Al-Mamun, Md; Masunaga, Shigeki

    2017-02-01

    Perfluoroalkyl acids (PFAAs) are persistent environmental pollutants that have been detected in various media including human serum. Due to concerns regarding their bioaccumulation and possible negative health effects, an understanding of routes of human exposure is necessary. PFAAs are recalcitrant in many water treatment processes, making drinking water a potential source of human exposure. This study presents the first report on contamination from PFAAs in river and drinking water in Ghana. The targeted PFAAs were perfluoroalkyl carboxylic acids (PFCAs) with C 4-14 carbon chain and perfluoroalkane sulphonic acids (PFSAs) with C 6, 8, 10 . Five PFAA congeners - PFOA, PFOS, PFHxA, PFDA and PFPeA - were commonly detected in river and tap water. The mean concentrations of ∑PFAAs in the Kakum and Pra Rivers were 281 and 398ng/L, while tap water (supplied from the treatment of water from those rivers) contained concentrations of 197 and 200ng/L, respectively. PFOA and PFOS constituted about 99% of the ∑PFAAs. The risk quotient (RQ) attributed to drinking of tap water was estimated at 1.01 and 1.74 for PFOA and PFOS, respectively. For a country that has not produced these compounds, the RQs were unexpectedly high, raising concerns particularly about contamination from such emerging pollutants in local water sources. The study revealed limitations of local tap water treatment in getting rid of these emerging pollutants. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Maternal and Neonatal Levels of Perfluoroalkyl Substances in Relation to Gestational Weight Gain

    Directory of Open Access Journals (Sweden)

    Jillian Ashley-Martin

    2016-01-01

    Full Text Available Perfluoroalkyl substances (PFASs are ubiquitous, persistent pollutants widely used in the production of common household and consumer goods. There is a limited body of literature suggesting that these chemicals may alter metabolic pathways and growth trajectories. The relationship between prenatal exposures to these chemicals and gestational weight gain (GWG has received limited attention. One objective was to analyze the associations among maternal plasma levels of three common perfluoroalkyl substances (perfluorooctanoate (PFOA, perfluorooctanesulfonate (PFOS, perfluorohexanesulfanoate (PFHxS and GWG. Additionally, we explored whether GWG was associated with cord blood PFAS levels. This study utilized data collected in the Maternal-Infant Research on Environmental Chemicals (MIREC Study, a trans-Canada cohort study of 2001 pregnant women. Our analysis quantified associations between (1 maternal PFAS concentrations and GWG and (2 GWG and cord blood PFAS concentrations. Maternal PFOS concentrations were positively associated with GWG (β = 0.39 95% CI: 0.02, 0.75. Interquartile increases in GWG were significantly associated with elevated cord blood PFOA (OR = 1.33; 95% CI: 1.13 to 1.56 and PFOS (OR = 1.20; 95% CI: 1.03 to 1.40 concentrations. No statistically significant associations were observed between GWG and either measure of PFHxS. These findings warrant elucidation of the potential underlying mechanisms.

  19. Role of wastewater treatment plant (WWTP in environmental cycling of poly- and perfluoroalkyl (PFAS compounds

    Directory of Open Access Journals (Sweden)

    Hanna Hamid

    2016-11-01

    Full Text Available The role of wastewater treatment plant (WWTP in environmental cycling of the poly- and perfluoroalkyl compounds (PFASs through the aqueous effluent, sludge and air emission has been critically reviewed here. Understanding the role WWTPs can provide better understanding of global cycling of persistent PFASs and assist in formulating relevant environmental policies. The review suggested that, the WWTP effluent is a major source of perfluoroalkyl acids (PFAAs in surface water. Land application of biosolids (treated sludge have shown preferential bioaccumulation of short chain (

  20. Survey of perfluoroalkyl acids (PFAAs) and their precursors present in Japanese consumer products.

    Science.gov (United States)

    Ye, Feng; Zushi, Yasuyuki; Masunaga, Shigeki

    2015-05-01

    Perfluoroalkyl acids (PFAAs) and their precursors have been used in various consumer products. However, limited information regarding their occurrence and concentration levels in products is available. In this study, we investigated 18 PFAAs and 14 PFAA precursors in various categories of consumer products purchased in Japan. Relatively high total concentrations of PFAAs and their precursors were found in sprays for fabrics and textiles (car wash/coating products (perfluoroalkyl carboxylic acids (PFCAs) (carbon chain length⩾7) were also detected in greater concentrations than short chain PFCAs (⩽6). This result suggests that consumer products are one of the important sources of long-chain PFCAs in the environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Development of a method for the analysis of perfluoroalkylated compounds in whole blood

    Energy Technology Data Exchange (ETDEWEB)

    Kaerrman, A.; Bavel, B. van; Lindstroem, G. [Oerebro Univ. (Sweden). Man-Technology-Environmental Research Centre; Jaernberg, U. [Stockholm Univ. (Sweden). Inst. of Applied Environmental Research

    2004-09-15

    The commercialisation of interfaced high performance liquid chromatography mass spectrometry (HPLC-MS) facilitated selective and sensitive analysis of perfluoroalkylated (PFA) acids, a group of compounds frequently used for example as industrial surfactants and which are very persistent and biologically active, in a more convenient way than before. Since then a number of reports on PFA compounds found in humans and wildlife have been published. The most used technique for the analysis of perfluoroalkylated compounds has been ion-pair extraction followed by high performance liquid chromatography (HPLC) and negative electrospray tandem mass spectrometry (MS/MS). Tetrabutylammonium ion as the counter ion in the ion-pair extraction has been used together with GC-analysis, LC-fluorescence and LC-MS/MS. Recently, solid phase extraction (SPE) has been used instead of ion-pair extraction for the extraction of human serum. Previously reported studies on human exposure have mainly been on serum, probably because there are indications that PFA acids bind to plasma proteins. We here present a fast and simple method that involves SPE and which is suitable for extracting whole blood samples. Further more, 13 PFAs were included in the method, which uses HPLC and single quadropole mass spectrometry.

  2. Enhancing Safety through Generic Competencies

    Directory of Open Access Journals (Sweden)

    S. Mockel

    2014-03-01

    Full Text Available This article provides insights into proactive safety management and mitigation. An analysis of accident reports reveals categories of supervening causes of accidents which can be directly linked to the concept of generic competencies (information management, communication and coordination, problem solving, and effect control. These findings strongly suggest adding the human element as another safety-constituting pillar to the concept of ship safety next to technology and regulation. We argue that the human element has unique abilities in dealing with critical and highly dynamic situations which can contribute to the system's recovery from non-routine or critical situations. By educating seafarers in generic competencies we claim to enable the people onboard to successfully deal with critical situations.

  3. Efficacy of sulfonamides and Baycox(®) against Isospora suis in experimental infections of suckling piglets.

    Science.gov (United States)

    Joachim, Anja; Mundt, Hans-Christian

    2011-12-01

    Sulfonamide treatment of piglets against neonatal coccidiosis has frequently been suggested in the literature. In order to evaluate the efficacy of sulfonamides against experimental Isospora suis infections in suckling piglets (oral infection with 1,500 sporulated oocysts of I. suis per piglet on the fourth day of life), two trials were conducted. In trial I, oral sulfadimidine (group Sulfa-Oral) was applied in doses of 100 mg/kg of body weight (BW) 1 day before infection and 75 mg/kg BW daily for the following 5 days, and sulfamethoxypyrimidine (SMP) was applied parenterally in daily doses of 75 mg/kg BW for the same time period. In trial II, SMP was applied parenterally in doses of 75 mg/kg BW (a) from the day of infection daily for 7 days (SMP-Standard), (b) for 2 days starting on the day of infection (SMP-Early), (c) for 3 days starting 2 days post-infection (d.p.i.; SMP-Middle), (d) for 2 days starting 5 d.p.i. (SMP-Late), and (e) every other day from the day of infection until 6 d.p.i. (SMP-Alternating), as well as (f) orally in doses of 75 mg/kg BW from the day of infection for 7 days (SMP-Oral). The sulfonamide-treated groups were compared to a toltrazuril-treated group (single oral treatment with Baycox® 5% suspension, 20 mg/kg BW 2 d.p.i.) and to a water-treated Control group. Each group consisted of seven to nine piglets. The parameters evaluated were oocyst excretion and fecal consistency/diarrhea from 4 to 15 d.p.i. Sulfa-Oral, SMP-Early, and SMP-Late had no significant effect in reduction of oocyst excretion and diarrhea, whereas treatment for 3-7 days with SMP reduced both parasite shedding and diarrhea significantly. Oral treatment with SMP was comparable to parenteral application. Baycox® in a single application had the most pronounced effect and completely suppressed oocyst excretion and diarrhea during the examination period. It could be shown that repeated application of sulfonamides, provided that the appropriate time period after infection

  4. Adsorption of sulfonamides to demineralized pine wood biochars prepared under different thermochemical conditions

    International Nuclear Information System (INIS)

    Xie, Mengxing; Chen, Wei; Xu, Zhaoyi; Zheng, Shourong; Zhu, Dongqiang

    2014-01-01

    The main objective of this study was to understand the key factors and mechanisms controlling adsorption of sulfonamides to biochars. Batch adsorption experiments were performed for sulfamethoxazole and sulfapyridine to three pine-wood biochars prepared under different thermochemical conditions: pyrolysis at 400 °C (C400) and 500 °C (C500), and pyrolysis at 500 °C followed with hydrogenation (C500-H). For both sulfonamides, the adsorbent surface area-normalized adsorption was stronger to C500 than to C400. This is attributable to the enhanced π–π electron-donor–acceptor interaction with the carbon surface of C500 due to the higher degree of graphitization. Despite the relatively large difference in surface O-functionality content between C500 (12.2%) and C500-H (6.6%), the two biochars exhibited nearly identical adsorbent surface area-normalized adsorption, indicating negligible role of surface O-functionalities in the adsorption to these adsorbents. Effects of solution chemistry conditions (pH, Cu 2+ , and dissolved soil humic acid) on adsorption were examined. -- Highlights: • Adsorption to biochars is dominated by π–π electron-donor–acceptor (EDA) interaction. • Graphitic surfaces of biochars are predominant adsorption sites. • Surface O-functionalities of biochars play minor roles in adsorption. • Adsorption affinities are markedly affected by Cu ions and humic acids. -- Adsorption of sulfonamides to biochars is dominated by π–π electron-donor–acceptor (EDA) interaction with the graphitic surface

  5. Malaria parasite carbonic anhydrase: inhibition of aromatic/heterocyclic sulfonamides and its therapeutic potential

    Science.gov (United States)

    Krungkrai, Sudaratana R; Krungkrai, Jerapan

    2011-01-01

    Plasmodium falciparum (P. falciparum) is responsible for the majority of life-threatening cases of human malaria, causing 1.5-2.7 million annual deaths. The global emergence of drug-resistant malaria parasites necessitates identification and characterization of novel drug targets and their potential inhibitors. We identified the carbonic anhydrase (CA) genes in P. falciparum. The pfCA gene encodes anα-carbonic anhydrase, a Zn2+-metalloenzme, possessing catalytic properties distinct from that of the human host CA enzyme. The amino acid sequence of the pfCA enzyme is different from the analogous protozoan and human enzymes. A library of aromatic/heterocyclic sulfonamides possessing a large diversity of scaffolds were found to be very good inhibitors for the malarial enzyme at moderate-low micromolar and submicromolar inhibitions. The structure of the groups substituting the aromatic-ureido- or aromatic-azomethine fragment of the molecule and the length of the parent sulfonamide were critical parameters for the inhibitory properties of the sulfonamides. One derivative, that is, 4- (3, 4-dichlorophenylureido)thioureido-benzenesulfonamide (compound 10) was the most effective in vitro Plasmodium falciparum CA inhibitor, and was also the most effective antimalarial compound on the in vitro P. falciparum growth inhibition. The compound 10 was also effective in vivo antimalarial agent in mice infected with Plasmodium berghei, an animal model of drug testing for human malaria infection. It is therefore concluded that the sulphonamide inhibitors targeting the parasite CA may have potential for the development of novel therapies against human malaria. PMID:23569766

  6. Thermodynamic aspects of solubility and partitioning processes of some sulfonamides in the solvents modeling biological media

    International Nuclear Information System (INIS)

    Perlovich, German L.; Ryzhakov, Alex M.; Strakhova, Nadezda N.; Kazachenko, Vladimir P.; Schaper, Klaus-Jürgen; Raevsky, Oleg A.

    2014-01-01

    Highlights: • Solubility processes of some sulfonamide isomers in water and 1-octanol were investigated. • Transfer processes from water to 1-octanol were evaluated by analysis of enthalpic and entropic terms. • Impact of various substituents in phenyl rings on solubility and transfer processes was studied. -- Abstract: The thermodynamic aspects of solubility processes of sulfonamides (SAs) with the general structures 4-NH 2 –C 6 H 4 –SO 2 NH–C 6 H 2 (R 1 )(R 2 )-R 3 (R 1 = 2-CH 3 , 2-Cl; R 2 = 4-CH 3 , 4-Cl; R 3 =5-H, 5-Cl), 4-NH 2 -2-Cl–C 6 H 3 –SO 2 NH–C 6 H 3 (R 1 )-R 2 (R 1 = 2-H, 2-Cl; R 2 = 4-H, 4-Cl) and 4-NH 2 -2-CH 3 –C 6 H 3 –SO 2 NH–C 6 H 3 (R 1 )-R 2 (R 1 = 2-H, 2-Cl, 2-NO 2 ; R 2 = 4-H, 4-Cl) in water and 1-octanol (as phases modeling various drug delivery pathways) were studied using the isothermal saturation method. For the sulfonamides with various substituents in phenyl rings the processes of transfer from water to 1-octanol were studied by a diagram method combined with analysis of enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is possible through the present approach, leads to the insight that the contribution of these terms is different for different molecules (entropy- or enthalpy-determined). Thus, in contrast to the interpretation of only the Gibbs energy of transfer (extensively used for pharmaceuticals in the form of the partition coefficient, logP), the analysis of thermodynamic functions of the transfer process provides additional mechanistic information. This may be important for further evaluation of the physiological distribution of drug molecules and may provide a better understanding of biopharmaceutical properties of drugs

  7. Novel 1,4-naphthoquinone-based sulfonamides: Synthesis, QSAR, anticancer and antimalarial studies.

    Science.gov (United States)

    Pingaew, Ratchanok; Prachayasittikul, Veda; Worachartcheewan, Apilak; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

    2015-10-20

    A novel series of 1,4-naphthoquinones (33-44) tethered by open and closed chain sulfonamide moieties were designed, synthesized and evaluated for their cytotoxic and antimalarial activities. All quinone-sulfonamide derivatives displayed a broad spectrum of cytotoxic activities against all of the tested cancer cell lines including HuCCA-1, HepG2, A549 and MOLT-3. Most quinones (33-36 and 38-43) exerted higher anticancer activity against HepG2 cell than that of the etoposide. The open chain analogs 36 and 42 were shown to be the most potent compounds. Notably, the restricted sulfonamide analog 38 with 6,7-dimethoxy groups exhibited the most potent antimalarial activity (IC₅₀ = 2.8 μM). Quantitative structure-activity relationships (QSAR) study was performed to reveal important chemical features governing the biological activities. Five constructed QSAR models provided acceptable predictive performance (Rcv 0.5647-0.9317 and RMSEcv 0.1231-0.2825). Four additional sets of structurally modified compounds were generated in silico (34a-34d, 36a-36k, 40a-40d and 42a-42k) in which their activities were predicted using the constructed QSAR models. A comprehensive discussion of the structure-activity relationships was made and a set of promising compounds (i.e., 33, 36, 38, 42, 36d, 36f, 42e, 42g and 42f) was suggested for further development as anticancer and antimalarial agents. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  8. Design, synthesis, characterization and computational docking studies of novel sulfonamide derivatives.

    Science.gov (United States)

    Saleem, Hira; Maryam, Arooma; Bokhari, Saleem Ahmed; Ashiq, Ayesha; Rauf, Sadaf Abdul; Khalid, Rana Rehan; Qureshi, Fahim Ashraf; Siddiqi, Abdul Rauf

    2018-01-01

    This study reports three novel sulfonamide derivatives 4-Chloro-N-[(4-methylphenyl) sulphonyl]-N-propyl benzamide ( 1A ), N-(2-hydroxyphenyl)-4-methyl benzene sulfonamide ( 1B ) and 4-methyl-N-(2-nitrophenyl) benzene sulfonamide ( 1C ). The compounds were synthesised from starting material 4-methylbenzenesulfonyl chloride and their structure was studied through 1 H-NMR and 13 C-NMR spectra. Computational docking was performed to estimate their binding energy against bacterial p -amino benzoic acid (PABA) receptor, the dihydropteroate synthase (DHPS). The derivatives were tested in vitro for their antimicrobial activity against Gram+ and Gram- bacteria including E. coli, B. subtilis, B. licheniformis and B. linen. 1A was found active only against B. linen ; 1B was effective against E. coli, B. subtilis and B. linen whereas 1C showed activity against E. coli, B. licheniformis and B. linen . 1C showed maximum activity with minimum inhibitory concentration (MIC) of 50, 100 and 150 µg/mL against E. coli, B. licheniformis and B. linen respectively. 1C exhibited maximum affinity to DHPS with binding free energy of -8.1 kcal/mol. It enriched in the top 0.5 % of a library of 7663 compounds, ranked in order of their binding affinity against DHPS. 1C was followed by 1B which showed a moderate to low level MIC of 100, 250 and 150 µg/mL against E. coli, B. subtilis and B. linen respectively, whereas 1A showed a moderate level MIC of 100 µg/mL but only against B. linen . These derivatives may thus serve as potential anti-bacterial alternatives against resistant pathogens.

  9. Antimicrobial activity of some sulfonamide derivatives on clinical isolates of Staphylococus aureus

    Directory of Open Access Journals (Sweden)

    Bekdemir Yunus

    2008-08-01

    Full Text Available Abstract Background Staphylococcus aureus is a non-motile, gram positive, non-sporforming, facultative anaerobic microorganism. It is one of the important bacteria as a potential pathogen specifically for nosocomial infections. The sulfonamide derivative medicines are preferred to cure infection caused by S. aureus due to methicillin resistance. Methods Antimicrobial activity of four sulfonamide derivatives have been investigated against 50 clinical isolates of S. aureus and tested by using MIC and disc diffusion methods. 50 clinical isolate which collected from specimens of patients who are given medical treatment in Ondokuz Mayis University Medical School Hospital. A control strain of S. aureus ATCC 29213 was also tested. Results The strongest inhibition was observed in the cases of I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid], and II [N-(2-hydroxy-5-nitro-phenyl-4-methyl-benzensulfonamid] against S. aureus. Compound I [N-(2-hydroxy-4-nitro-phenyl-4-methyl-benzensulfonamid] showed higher effect on 21 S. aureus MRSAisolates than oxacillin antibiotic. Introducing an electron withdrawing on the ring increased the antimicrobial activity remarkably. Conclusion This study may help to suggest an alternative possible leading compound for development of new antimicrobial agents against MRSA and MSSA resistant S. aureus. It was also shown here that that clinical isolates of 50 S. aureus have various resistance patterns against to four sulfonamide derivatives. It may also be emphasized here that in vitro antimicrobial susceptibility testing results for S. aureus need standardization with further studies and it should also have a correlation with in vivo therapeutic response experiments.

  10. Synthesis and characterization of curcumin-sulfonamide hybrids: Biological evaluation and molecular docking studies

    Science.gov (United States)

    Banuppriya, Govindharasu; Sribalan, Rajendran; Padmini, Vediappen

    2018-03-01

    Curcumin-sulfonamide hybrids (4a-e) were synthesized and their in vitro antioxidant, anti-inflammatory and anticancer activities were studied. The synthesized compounds showed a very good potent activity towards antioxidant and anti-inflammatory studies rather than its parent as well as standard. These compounds have exhibited an excellent toxicity effect to the cancer cell lines such as A549 and AGS. The compounds 4a and 4c have showed good anticancer activity than curcumin. The molecular docking studies were also performed against various Epidermal Growth Factor Receptor (EGFR) enzymes. The DFT calculations were also done in order to support the docking results.

  11. Determination of sulfonamides and trimethoprim using high temperature HPLC with simultaneous temperature and solvent gradient.

    Science.gov (United States)

    Giegold, Sascha; Teutenberg, Thorsten; Tuerk, Jochen; Kiffmeyer, Thekla; Wenclawiak, Bernd

    2008-10-01

    A fast HPLC method for the analysis of eight selected sulfonamides (SA) and trimethoprim has been developed with the use of high temperature HPLC. The separation could be achieved in less than 1.5 min on a 50 mm sub 2 microm column with simultaneous solvent and temperature gradient programming. Due to the lower viscosity of the mobile phase and the increased mass transfer at higher temperatures, the separation could be performed on a conventional HPLC system obtaining peak widths at half height between 0.6 and 1.3 s.

  12. 4-Methyl-N-(1-methyl-1H-indazol-5-yl)benzene­sulfonamide

    Science.gov (United States)

    Chicha, Hakima; Oulemda, Bassou; Rakib, El Mostapha; Saadi, Mohamed; El Ammari, Lahcen

    2013-01-01

    In the title compound, C15H15N3O2S, the fused ring system is close to planar, the largest deviation from the mean plane being 0.030 (2) Å, and makes a dihedral angle of 48.84 (9)° with the benzene ring belonging to the methyl­benzene­sulfonamide moiety. In the crystal, mol­ecules are ­connected through N—H⋯N hydrogen bonds and weak C—H⋯O contacts, forming a two-dimensional network parallel to (001). PMID:24427093

  13. Development of an analytical method for determination of sulfonamide residues in eggs

    International Nuclear Information System (INIS)

    Ben Azzeddine, Chams

    2009-01-01

    For the determination of sulfonamide residues in eggs, Premitest is selected for screening, providing a qualitative biological approach, it is inexpensive, fast, multi-elements and easy to implement. The H. P.L.C. / UV is the quantitative method of choice for confirmation and determination of these contaminants. During my internship, I had the opportunity to participate in the development of this method. It is recognized slower and more expensive but more specific and more sensitive. In this report, I present this optimized method and some criteria checked during my internship. Other criteria are to be completed to validate the method that will be subsequently used for routine analysis.

  14. Preclinical evaluation of carbon-11 and fluorine-18 sulfonamide derivatives for in vivo radiolabeling of erythrocytes

    OpenAIRE

    Gheysens, Olivier; Akurathi, Vamsidhar; Chekol, Rufael; Dresselaers, Tom; Celen, Sofie; Koole, Michel; Dauwe, Dieter; Cleynhens, Bernard J; Claus, Piet; Janssens, Stefan; Verbruggen, Alfons M; Nuyts, Johan; Himmelreich, Uwe; Bormans, Guy M

    2013-01-01

    Background To date, few PET tracers for in vivo labeling of red blood cells (RBCs) are available. In this study, we report the radiosynthesis and in vitro and in vivo evaluation of 11C and 18F sulfonamide derivatives targeting carbonic anhydrase II (CA II), a metallo-enzyme expressed in RBCs, as potential blood pool tracers. A proof-of-concept in vivo imaging study was performed to demonstrate the feasibility to assess cardiac function and volumes using electrocardiogram (ECG)-gated positron ...

  15. Efficient synthesis of sulfonamide derivatives on solid supports catalyzed using solvent-free and microwave-assisted methods

    Energy Technology Data Exchange (ETDEWEB)

    Camargo-Ordonez, Argelia; Moreno-Reyes, Christian; Olazaran-Santibanez, Fabian; Martinez-Hernandez, Sheila; Bocanegra-Garcia, Virgilio; Rivera, Gildardo [Universidad Autonoma de Tamaulipas, Reynosa (Mexico). Dep. de Farmacia y Quimica Medicinal

    2011-07-01

    In this work we report the synthesis of sulfonamide derivatives using a conventional procedure and with solid supports, such as silica gel, florisil, alumina, 4A molecular sieves, montmorillonite KSF, and montmorillonite K10 using solvent-free and microwave-assisted methods. Our results show that solid supports have a catalytic activity in the formation of sulfonamide derivatives. We found that florisil, montmorillonite KSF, and K10 could be used as inexpensive alternative catalysts that are easily separated from the reaction media. Additionally, solvent-free and microwave-assisted methods were more efficient in reducing reaction time and in increasing yield. (author)

  16. Efficient synthesis of sulfonamide derivatives on solid supports catalyzed using solvent-free and microwave-assisted methods

    International Nuclear Information System (INIS)

    Camargo-Ordonez, Argelia; Moreno-Reyes, Christian; Olazaran-Santibanez, Fabian; Martinez-Hernandez, Sheila; Bocanegra-Garcia, Virgilio; Rivera, Gildardo

    2011-01-01

    In this work we report the synthesis of sulfonamide derivatives using a conventional procedure and with solid supports, such as silica gel, florisil, alumina, 4A molecular sieves, montmorillonite KSF, and montmorillonite K10 using solvent-free and microwave-assisted methods. Our results show that solid supports have a catalytic activity in the formation of sulfonamide derivatives. We found that florisil, montmorillonite KSF, and K10 could be used as inexpensive alternative catalysts that are easily separated from the reaction media. Additionally, solvent-free and microwave-assisted methods were more efficient in reducing reaction time and in increasing yield. (author)

  17. The role of the acidity of N-heteroaryl sulfonamides as inhibitors of bcl-2 family protein-protein interactions.

    Science.gov (United States)

    Touré, B Barry; Miller-Moslin, Karen; Yusuff, Naeem; Perez, Lawrence; Doré, Michael; Joud, Carol; Michael, Walter; DiPietro, Lucian; van der Plas, Simon; McEwan, Michael; Lenoir, Francois; Hoe, Madelene; Karki, Rajesh; Springer, Clayton; Sullivan, John; Levine, Kymberly; Fiorilla, Catherine; Xie, Xiaoling; Kulathila, Raviraj; Herlihy, Kara; Porter, Dale; Visser, Michael

    2013-02-14

    Overexpression of the antiapoptotic members of the Bcl-2 family of proteins is commonly associated with cancer cell survival and resistance to chemotherapeutics. Here, we describe the structure-based optimization of a series of N-heteroaryl sulfonamides that demonstrate potent mechanism-based cell death. The role of the acidic nature of the sulfonamide moiety as it relates to potency, solubility, and clearance is examined. This has led to the discovery of novel heterocyclic replacements for the acylsulfonamide core of ABT-737 and ABT-263.

  18. Automated analysis in generic groups

    Science.gov (United States)

    Fagerholm, Edvard

    This thesis studies automated methods for analyzing hardness assumptions in generic group models, following ideas of symbolic cryptography. We define a broad class of generic and symbolic group models for different settings---symmetric or asymmetric (leveled) k-linear groups --- and prove ''computational soundness'' theorems for the symbolic models. Based on this result, we formulate a master theorem that relates the hardness of an assumption to solving problems in polynomial algebra. We systematically analyze these problems identifying different classes of assumptions and obtain decidability and undecidability results. Then, we develop automated procedures for verifying the conditions of our master theorems, and thus the validity of hardness assumptions in generic group models. The concrete outcome is an automated tool, the Generic Group Analyzer, which takes as input the statement of an assumption, and outputs either a proof of its generic hardness or shows an algebraic attack against the assumption. Structure-preserving signatures are signature schemes defined over bilinear groups in which messages, public keys and signatures are group elements, and the verification algorithm consists of evaluating ''pairing-product equations''. Recent work on structure-preserving signatures studies optimality of these schemes in terms of the number of group elements needed in the verification key and the signature, and the number of pairing-product equations in the verification algorithm. While the size of keys and signatures is crucial for many applications, another aspect of performance is the time it takes to verify a signature. The most expensive operation during verification is the computation of pairings. However, the concrete number of pairings is not captured by the number of pairing-product equations considered in earlier work. We consider the question of what is the minimal number of pairing computations needed to verify structure-preserving signatures. We build an

  19. Electron Spin Resonance Studies of Carbonic Anhydrase: Transition Metal Ions and Spin-Labeled Sulfonamides*

    Science.gov (United States)

    Taylor, June S.; Mushak, Paul; Coleman, Joseph E.

    1970-01-01

    Electron spin resonance (esr) spectra of Cu(II) and Co(II) carbonic anhydrase, and a spin-labeled sulfonamide complex of the Zn(II) enzyme, are reported. The coordination geometry of Cu(II) bound in the enzyme appears to have approximately axial symmetry. Esr spectra of enzyme complexes with metal-binding anions also show axial symmetry and greater covalency, in the order ethoxzolamide cyanide complex suggests the presence of two, and probably three, equivalent nitrogen ligands from the protein. Esr spectra of the Co(II) enzyme and its complexes show two types of Co(II) environment, one typical of the native enzyme and the 1:1 CN- complex, and one typical of a 2:1 CN- complex. Co(II) in the 2:1 complex appears to be low-spin and probably has a coordination number of 5. Binding of a spin-labeled sulfonamide to the active center immobilizes the free radical. The similarity of the esr spectra of spin-labeled Zn(II) and Co(II) carbonic anhydrases suggests that the conformation at the active center is similar in the two metal derivatives. PMID:4320976

  20. Removal of tetracyclines, sulfonamides, and quinolones by industrial-scale composting and anaerobic digestion processes.

    Science.gov (United States)

    Liu, Hang; Pu, Chengjun; Yu, Xiaolu; Sun, Ying; Chen, Junhao

    2018-02-15

    This study evaluated and compared the removal of antibiotics by industrial-scale composting and anaerobic digestion at different seasons. Twenty compounds belonged to three classes of widely used veterinary antibiotics (i.e., tetracyclines, sulfonamides, and quinolones) were investigated. Results show that of the three groups of antibiotics, tetracyclines were dominant in swine feces and poorly removed by anaerobic digestion with significant accumulation in biosolids, particularly in winter. Compared to that in winter, a much more effective removal (> 97%) by anaerobic digestion was observed for sulfonamides in summer. By contrast, quinolones were the least abundant antibiotics in swine feces and exhibited a higher removal by anaerobic digestion in winter than in summer. The overall removal of antibiotics by aerobic composting could be more than 90% in either winter or summer. Nevertheless, compost products from livestock farms in Beijing contained much higher antibiotics than commercial organic fertilizers. Thus, industrial composting standards should be strictly applied to livestock farms to further remove antibiotics and produce high quality organic fertilizer.

  1. Development and Characterization of Novel Films Based on Sulfonamide-Chitosan Derivatives for Potential Wound Dressing

    Directory of Open Access Journals (Sweden)

    Oana Maria Dragostin

    2015-12-01

    Full Text Available The objective of this study was to develop new films based on chitosan functionalized with sulfonamide drugs (sulfametoxydiazine, sulfadiazine, sulfadimetho-xine, sulfamethoxazol, sulfamerazine, sulfizoxazol in order to enhance the biological effects of chitosan. The morphology and physical properties of functionalized chitosan films as well the antioxidant effects of sulfonamide-chitosan derivatives were investigated. The chitosan-derivative films showed a rough surface and hydrophilic properties, which are very important features for their use as a wound dressing. The film based on chitosan-sulfisoxazol (CS-S6 showed the highest swelling ratio (197% and the highest biodegradation rate (63.04% in comparison to chitosan film for which the swelling ratio was 190% and biodegradation rate was only 10%. Referring to the antioxidant effects the most active was chitosan-sulfamerazine (CS-S5 which was 8.3 times more active than chitosan related to DPPH (1,1-diphenyl-2-picrylhydrazyl radical scavenging ability. This compound showed also a good ferric reducing power and improved total antioxidant capacity.

  2. Rapid startup of thermophilic anaerobic digester to remove tetracycline and sulfonamides resistance genes from sewage sludge.

    Science.gov (United States)

    Xu, Rui; Yang, Zhao-Hui; Wang, Qing-Peng; Bai, Yang; Liu, Jian-Bo; Zheng, Yue; Zhang, Yan-Ru; Xiong, Wei-Ping; Ahmad, Kito; Fan, Chang-Zheng

    2018-01-15

    Spread of antibiotic resistance genes (ARGs) originating from sewage sludge is highlighted as an eminent health threat. This study established a thermophilic anaerobic digester using one-step startup strategy to quickly remove tetracycline and sulfonamides resistance genes from sewage sludge. At least 20days were saved in the startup period from mesophilic to thermophilic condition. Based on the results of 16S rDNA amplicons sequencing and predicted metagenomic method, the successful startup largely relied on the fast colonization of core thermophilic microbial population (e.g. Firmicutes, Proteobacteria, Actinobacteria). Microbial metabolic gene pathways for substrate degradation and methane production was also increased by one-step mode. In addition, real-time quantitative PCR approach revealed that most targeted tetracycline and sulfonamides resistance genes ARGs (sulI, tetA, tetO, tetX) were substantially removed during thermophilic digestion (removal efficiency>80%). Network analysis showed that the elimination of ARGs was attributed to the decline of their horizontal (intI1 item) and vertical (potential hosts) transfer-related elements under high-temperature. This research demonstrated that rapid startup thermophilic anaerobic digestion of wastewater solids would be a suitable technology for reducing quantities of various ARGs. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Preliminary investigation on the occurrence of several sulfonamide antibiotics in the Haihe River Basin of China

    Science.gov (United States)

    Zhang, S. L.; Zhang, J.; Wang, Z. G.; Wang, Y. Z.; Liang, S. T.; Liu, C.; Wang, Z.

    2017-08-01

    Several samples collected from lakes, rivers and reservoirs in Haihe river basin of China were analyzed for 8 sulfonamide antibiotics by using solid-phase extraction and liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). All water samples were enriched with HLB extraction cartridges. The antibiotics were separated by gradient elution with methanol as the mobile phase adding 0.1% formic acid. The eluate was then analyzed by the mode of multiple reaction monitoring (MRM). The limits of detection (LOD) and quantification (LOQ) were 0.4-1.0 ng/L and 1.0-3.0 ng/L respectively. The method was used for the analysis of 13 samples from Haihe river basin in China. The results showed that sulfamethoxazole was present in all water samples with maximum concentration of 107.59 ng/L. Sulfadiazine was also frequently detected, concentrations ranging from 2.81 ng/L to 85.35 ng/L. Other sulfonamide antibiotics were not detected in most water samples, especially for those samples from drinking water resources.

  4. Spectroscopic characterization, antimicrobial activity, DFT computation and docking studies of sulfonamide Schiff bases

    Science.gov (United States)

    Mondal, Sudipa; Mandal, Santi M.; Mondal, Tapan Kumar; Sinha, Chittaranjan

    2017-01-01

    Schiff bases synthesised from the condensation of 2-(hydroxy)naphthaldehyde and sulfonamides (sufathiazole (STZ), sulfapyridine (SPY), sulfadiazine (SDZ), sulfamerazine (SMZ) and sulfaguanidine (SGN)) are characterized by different spectroscopic data (FTIR, UV-Vis, Mass, NMR) and two of them, (E)-4-(((2-hydroxynaphthalen-1-yl)methylene)amino)-N-(thiazol-2-yl)benzenesulfonamide (1a) and (E)-N-(diaminomethylene)-4-(((2-hydroxynaphthalen-1-yl)methylene)amino)benzenesulfonamide (1e) have been confirmed by single crystal X-ray structure determination. Antimicrobial activities of the Schiff bases have been evaluated against certified and resistant Gram positive (Staphylococcus aureus, Enterococcus facelis) and Gram negative (Streptococcus pyogenes, Salmonella typhi, Shigella dysenteriae, Shigella flexneri, Klebsiella pneumonia) pathogens. Performance of Schiff base against the resistant pathogens are better than standard stain and MIC data lie 32-128 μg/ml while parent sulfonamides are effectively inactive (MIC >512 μg/ml). The DFT optimized structures of the Schiff bases have been used to accomplish molecular docking studies with DHPS (dihydropteroate synthase) protein structure (downloaded from Protein Data Bank) to establish the most preferred mode of interaction. ADMET filtration, Cytotoxicity (MTT assay) and haemolysis assay have been examined for evaluation of druglike character.

  5. Elimination patterns of worldwide used sulfonamides and tetracyclines during anaerobic fermentation.

    Science.gov (United States)

    Spielmeyer, Astrid; Breier, Bettina; Groißmeier, Kathrin; Hamscher, Gerd

    2015-10-01

    Antibiotics such as sulfonamides and tetracyclines are frequently used in veterinary medicine. Due to incomplete absorption in the animal gut and/or unmetabolized excretion, the substances can enter the environment by using manure as soil fertilizer. The anaerobic fermentation process of biogas plants is discussed as potential sink for antibiotic compounds. However, negative impacts of antibiotics on the fermentation process are suspected. The elimination of sulfadiazine, sulfamethazine, tetracycline and chlortetracycline in semi-continuous lab-scale fermenters was investigated. Both biogas production and methane yield were not negatively affected by concentrations up to 38 mg per kg for sulfonamides and 7 mg per kg for tetracyclines. All substances were partly eliminated with elimination rates between 14% and 89%. Both matrix and structure of the target molecule influenced the elimination rate. Chlortetracycline was mainly transformed into iso-chlortetracycline. In all other cases, the elimination pathways remained undiscovered; however, sorption processes seem to have a negligible impact. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Impact of manure-related DOM on sulfonamide transport in arable soils

    Science.gov (United States)

    Zhou, Dan; Thiele-Bruhn, Sören; Arenz-Leufen, Martina Gesine; Jacques, Diederik; Lichtner, Peter; Engelhardt, Irina

    2016-09-01

    Field application of livestock manure introduces colloids and veterinary antibiotics, e.g. sulfonamides (SAs), into farmland. The presence of manure colloids may potentially intensify the SAs-pollution to soils and groundwater by colloid-facilitated transport. Transport of three SAs, sulfadiazine (SDZ), sulfamethoxypyridazine (SMPD), and sulfamoxole (SMOX), was investigated in saturated soil columns with and without manure colloids from sows and farrows, weaners, and fattening pigs. Experimental results showed that colloid-facilitated transport of SMOX was significant in the presence of manure colloids from fattening pigs with low C/N ratio, high SUVA280 nm and protein C, while manure colloids from sows and farrows and weaners had little effect on SMOX transport. In contrast, only retardation was observed for SDZ and SMPD when manure colloids were present. Breakthrough curves (BTCs) of colloids and SAs were replicated well by a newly developed numerical model that considers colloid-filtration theory, competitive kinetic sorption, and co-transport processes. Model results demonstrate that mobile colloids act as carriers for SMOX, while immobile colloids block SMOX from sorbing onto the soil. The low affinity of SMOX to sorb on immobile colloids prevents aggregation and also promotes SMOX's colloid-facilitated transport. Conversely, the high affinity of SDZ and SMPD to sorb on all types of immobile colloids retarded their transport. Thus, manure properties play a fundamental role in increasing the leaching risk of hydrophobic sulfonamides.

  7. Soil bacterial consortia and previous exposure enhance the biodegradation of sulfonamides from pig manure.

    Science.gov (United States)

    Islas-Espinoza, Marina; Reid, Brian J; Wexler, Margaret; Bond, Philip L

    2012-07-01

    Persistence or degradation of synthetic antibiotics in soil is crucial in assessing their environmental risks. Microbial catabolic activity in a sandy loamy soil with pig manure using 12C- and 14C-labelled sulfamethazine (SMZ) respirometry showed that SMZ was not readily degradable. But after 100 days, degradation in sulfadiazine-exposed manure was 9.2%, far greater than soil and organic manure (0.5% and 0.11%, respectively, p library from the treatment with highest degradation showed that most bacteria belonged to α, β and γ classes of Proteobacteria, Firmicutes, Bacteroidetes and Acidobacteria. Proteobacteria (α, β and γ), Firmicutes and Bacteroidetes which were the most abundant classes on day 1 also decreased most following prolonged exposure. From the matrix showing the highest degradation rate, 17 SMZ-resistant isolates biodegraded low levels of 14C-labelled SMZ when each species was incubated separately (0.2-1.5%) but biodegradation was enhanced when the four isolates with the highest biodegradation were incubated in a consortium (Bacillus licheniformis, Pseudomonas putida, Alcaligenes sp. and Aquamicrobium defluvium as per 16S rRNA gene sequencing), removing up to 7.8% of SMZ after 20 days. One of these species (B. licheniformis) was a known livestock and occasional human pathogen. Despite an environmental role of these species in sulfonamide bioremediation, the possibility of horizontal transfer of pathogenicity and resistance genes should caution against an indiscriminate use of these species as sulfonamide degraders.

  8. Generic Crystalline Disposal Reference Case

    Energy Technology Data Exchange (ETDEWEB)

    Painter, Scott Leroy [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Chu, Shaoping [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Harp, Dylan Robert [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Perry, Frank Vinton [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Wang, Yifeng [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2015-02-20

    A generic reference case for disposal of spent nuclear fuel and high-level radioactive waste in crystalline rock is outlined. The generic cases are intended to support development of disposal system modeling capability by establishing relevant baseline conditions and parameters. Establishment of a generic reference case requires that the emplacement concept, waste inventory, waste form, waste package, backfill/buffer properties, EBS failure scenarios, host rock properties, and biosphere be specified. The focus in this report is on those elements that are unique to crystalline disposal, especially the geosphere representation. Three emplacement concepts are suggested for further analyses: a waste packages containing 4 PWR assemblies emplaced in boreholes in the floors of tunnels (KBS-3 concept), a 12-assembly waste package emplaced in tunnels, and a 32-assembly dual purpose canister emplaced in tunnels. In addition, three failure scenarios were suggested for future use: a nominal scenario involving corrosion of the waste package in the tunnel emplacement concepts, a manufacturing defect scenario applicable to the KBS-3 concept, and a disruptive glaciation scenario applicable to both emplacement concepts. The computational approaches required to analyze EBS failure and transport processes in a crystalline rock repository are similar to those of argillite/shale, with the most significant difference being that the EBS in a crystalline rock repository will likely experience highly heterogeneous flow rates, which should be represented in the model. The computational approaches required to analyze radionuclide transport in the natural system are very different because of the highly channelized nature of fracture flow. Computational workflows tailored to crystalline rock based on discrete transport pathways extracted from discrete fracture network models are recommended.

  9. Investigating sources and pathways of perfluoroalkyl acids (PFAAs) in aquifers in Tokyo using multiple tracers

    International Nuclear Information System (INIS)

    Kuroda, Keisuke; Murakami, Michio; Oguma, Kumiko; Takada, Hideshige; Takizawa, Satoshi

    2014-01-01

    We employed a multi-tracer approach to investigate sources and pathways of perfluoroalkyl acids (PFAAs) in urban groundwater, based on 53 groundwater samples taken from confined aquifers and unconfined aquifers in Tokyo. While the median concentrations of groundwater PFAAs were several ng/L, the maximum concentrations of perfluorooctane sulfonate (PFOS, 990 ng/L), perfluorooctanoate (PFOA, 1800 ng/L) and perfluorononanoate (PFNA, 620 ng/L) in groundwater were several times higher than those of wastewater and street runoff reported in the literature. PFAAs were more frequently detected than sewage tracers (carbamazepine and crotamiton), presumably owing to the higher persistence of PFAAs, the multiple sources of PFAAs beyond sewage (e.g., surface runoff, point sources) and the formation of PFAAs from their precursors. Use of multiple methods of source apportionment including principal component analysis–multiple linear regression (PCA–MLR) and perfluoroalkyl carboxylic acid ratio analysis highlighted sewage and point sources as the primary sources of PFAAs in the most severely polluted groundwater samples, with street runoff being a minor source (44.6% sewage, 45.7% point sources and 9.7% street runoff, by PCA–MLR). Tritium analysis indicated that, while young groundwater (recharged during or after the 1970s, when PFAAs were already in commercial use) in shallow aquifers (< 50 m depth) was naturally highly vulnerable to PFAA pollution, PFAAs were also found in old groundwater (recharged before the 1950s, when PFAAs were not in use) in deep aquifers (50–500 m depth). This study demonstrated the utility of multiple uses of tracers (pharmaceuticals and personal care products; PPCPs, tritium) and source apportionment methods in investigating sources and pathways of PFAAs in multiple aquifer systems. - Highlights: • Aquifers in Tokyo had high levels of perfluoroalkyl acids (up to 1800 ng/L). • PFAAs were more frequently detected than sewage

  10. Investigating sources and pathways of perfluoroalkyl acids (PFAAs) in aquifers in Tokyo using multiple tracers

    Energy Technology Data Exchange (ETDEWEB)

    Kuroda, Keisuke, E-mail: keisukekr@gmail.com [Department of Urban Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656 (Japan); Murakami, Michio [Institute of Industrial Science, The University of Tokyo, 4-6-1 Komaba, Meguro, Tokyo 153-8505 (Japan); Oguma, Kumiko [Department of Urban Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656 (Japan); Takada, Hideshige [Laboratory of Organic Geochemistry (LOG), Institute of Symbiotic Science and Technology, Tokyo University of Agriculture and Technology, Fuchu, Tokyo 183-8509 (Japan); Takizawa, Satoshi [Department of Urban Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8656 (Japan)

    2014-08-01

    We employed a multi-tracer approach to investigate sources and pathways of perfluoroalkyl acids (PFAAs) in urban groundwater, based on 53 groundwater samples taken from confined aquifers and unconfined aquifers in Tokyo. While the median concentrations of groundwater PFAAs were several ng/L, the maximum concentrations of perfluorooctane sulfonate (PFOS, 990 ng/L), perfluorooctanoate (PFOA, 1800 ng/L) and perfluorononanoate (PFNA, 620 ng/L) in groundwater were several times higher than those of wastewater and street runoff reported in the literature. PFAAs were more frequently detected than sewage tracers (carbamazepine and crotamiton), presumably owing to the higher persistence of PFAAs, the multiple sources of PFAAs beyond sewage (e.g., surface runoff, point sources) and the formation of PFAAs from their precursors. Use of multiple methods of source apportionment including principal component analysis–multiple linear regression (PCA–MLR) and perfluoroalkyl carboxylic acid ratio analysis highlighted sewage and point sources as the primary sources of PFAAs in the most severely polluted groundwater samples, with street runoff being a minor source (44.6% sewage, 45.7% point sources and 9.7% street runoff, by PCA–MLR). Tritium analysis indicated that, while young groundwater (recharged during or after the 1970s, when PFAAs were already in commercial use) in shallow aquifers (< 50 m depth) was naturally highly vulnerable to PFAA pollution, PFAAs were also found in old groundwater (recharged before the 1950s, when PFAAs were not in use) in deep aquifers (50–500 m depth). This study demonstrated the utility of multiple uses of tracers (pharmaceuticals and personal care products; PPCPs, tritium) and source apportionment methods in investigating sources and pathways of PFAAs in multiple aquifer systems. - Highlights: • Aquifers in Tokyo had high levels of perfluoroalkyl acids (up to 1800 ng/L). • PFAAs were more frequently detected than sewage

  11. GLAD: a generic lattice debugger

    International Nuclear Information System (INIS)

    Lee, M.J.

    1992-01-01

    Today, numerous simulation and analysis codes exist for the design, commission, and operation of accelerator beam lines. There is a need to develop a common user interface and database link to run these codes interactively. This paper will describe a proposed system, GLAD (Generic LAttice Debugger), to fulfill this need. Specifically, GLAD can be used to find errors in beam lines during commissioning, control beam parameters during operation, and design beam line optics and error correction systems for the next generation of linear accelerators and storage rings. (author)

  12. Generic maximum likely scale selection

    DEFF Research Database (Denmark)

    Pedersen, Kim Steenstrup; Loog, Marco; Markussen, Bo

    2007-01-01

    in this work is on applying this selection principle under a Brownian image model. This image model provides a simple scale invariant prior for natural images and we provide illustrative examples of the behavior of our scale estimation on such images. In these illustrative examples, estimation is based......The fundamental problem of local scale selection is addressed by means of a novel principle, which is based on maximum likelihood estimation. The principle is generally applicable to a broad variety of image models and descriptors, and provides a generic scale estimation methodology. The focus...

  13. Thermodynamic aspects of solubility, solvation and partitioning processes of some sulfonamides

    Energy Technology Data Exchange (ETDEWEB)

    Perlovich, German L., E-mail: glp@isc-ras.r [Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka (Russian Federation); Institute of Solution Chemistry, Russian Academy of Sciences, 153045 Ivanovo (Russian Federation); Ryzhakov, Alex M. [Institute of Solution Chemistry, Russian Academy of Sciences, 153045 Ivanovo (Russian Federation); Strakhova, Nadezda N.; Kazachenko, Vladimir P. [Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka (Russian Federation); Schaper, Klaus-Juergen [Research Center Borstel, Leibniz Center for Medicine and Biosciences, D-23845 Borstel (Germany); Raevsky, Oleg A. [Department of Computer-Aided Molecular Design, Institute of Physiologically Active Compounds, Russian Academy of Sciences, 142432 Chernogolovka (Russian Federation)

    2011-05-15

    Research highlights: {yields} The thermodynamic aspects of sublimation processes of some sulfonamides were studied by investigating the temperature dependence of vapor pressure using the transpiration method. {yields} Solubility processes of the compounds in water, phosphate buffer with pH 7.4 and n-octanol were investigated and corresponding thermodynamic functions were calculated as well. {yields} Thermodynamic characteristics of the sulfonamides solvation were evaluated. - Abstract: The thermodynamic aspects of sublimation processes of three sulfonamides with the general structures C{sub 6}H{sub 5}-SO{sub 2}NH-C{sub 6}H{sub 4}-R (R = 4-NO{sub 2}) and 4-NH{sub 2}-C{sub 6}H{sub 4}-SO{sub 2}NH-C{sub 6}H{sub 4}-R (R = 4-NO{sub 2}; 4-CN) were studied by investigating the temperature dependence of vapor pressure using the transpiration method. These data together with those obtained earlier for C{sub 6}H{sub 5}-SO{sub 2}NH-C{sub 6}H{sub 4}-R (R = 4-Cl) and 4-NH{sub 2}-C{sub 6}H{sub 4}-SO{sub 2}NH-C{sub 6}H{sub 4}-R (R = 4-Cl; 4-OMe; 4-C{sub 2}H{sub 5}) were analyzed and compared. A correlation was derived between sublimation Gibbs free energies and the sum of H-bond acceptor factors of the molecules. Solubility processes of the compounds in water, phosphate buffer with pH 7.4 and n-octanol (as phases modeling various drug delivery pathways) were investigated and corresponding thermodynamic functions were calculated as well. Thermodynamic characteristics of the sulfonamides solvation were evaluated. Also in this case a correlation between solubility/solvation Gibbs free energy values and the sum of H-bond acceptor factors was observed. For the sulfonamides with various substituents at para-position the processes of transfer from one solvent (water or buffer) to n-octanol were studied by a diagram method combined with analysis of enthalpic and entropic terms. Distinguishing between enthalpy and entropy, as is possible through the present approach, leads to the insight

  14. Sulfonamide inhibition studies of two β-carbonic anhydrases from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2.

    Science.gov (United States)

    Vullo, Daniela; Lehneck, Ronny; Pöggeler, Stefanie; Supuran, Claudiu T

    2018-12-01

    The two β-carbonic anhydrases (CAs, EC 4.2.1.1) recently cloned and purified from the ascomycete fungus Sordaria macrospora, CAS1 and CAS2, were investigated for their inhibition with a panel of 39 aromatic, heterocyclic, and aliphatic sulfonamides and one sulfamate, many of which are clinically used agents. CAS1 was efficiently inhibited by tosylamide, 3-fluorosulfanilamide, and 3-chlorosulfanilamide (K I s in the range of 43.2-79.6 nM), whereas acetazolamide, methazolamide, topiramate, ethoxzolamide, dorzolamide, and brinzolamide were medium potency inhibitors (K I s in the range of 360-445 nM). CAS2 was less sensitive to sulfonamide inhibitors. The best CAS2 inhibitors were 5-amino-1,3,4-thiadiazole-2-sulfonamide (the deacetylated acetazolamide precursor) and 4-hydroxymethyl-benzenesulfonamide, with K I s in the range of 48.1-92.5 nM. Acetazolamide, dorzolamide, ethoxzolamide, topiramate, sulpiride, indisulam, celecoxib, and sulthiame were medium potency CAS2 inhibitors (K I s of 143-857 nM). Many other sulfonamides showed affinities in the high micromolar range or were ineffective as CAS1/2 inhibitors. Small changes in the structure of the inhibitor led to important differences of the activity. As these enzymes may show applications for the removal of anthropically generated polluting gases, finding modulators of their activity may be crucial for designing environmental-friendly CO 2 capture processes.

  15. Rapid method for quantification of nine sulfonamides in bovine milk using HPLC/MS/MS and without using SPE.

    Science.gov (United States)

    Nebot, Carolina; Regal, Patricia; Miranda, Jose Manuel; Fente, Cristina; Cepeda, Alberto

    2013-12-01

    Sulfonamides are antimicrobial agents widely employed in animal production and their residues in food could be an important risk to human health. In the dairy industry, large quantities of milk are monitored daily for the presence of sulfonamides. A simple and low-cost extraction protocol followed by a liquid chromatographic-tandem mass spectrometry method was developed for the simultaneous detection of nine sulfonamides in whole milk. The method was validated at the maximum residue limits established by European legislation. The limits of quantification obtained for most sulfonamides were between 12.5 and 25 μg kg(-1), detection capabilities ranged from 116 to 145 μg kg(-1), and recoveries, at 100 μg kg(-1), were greater than 89±12.5%. The method was employed to analyse 100 raw whole bovine milk samples collected from dairy farms in the northwest region of Spain. All of the samples were found to be compliant, but two were positive; one for sulfadiazine and the other for sulfamethoxipyridazine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Accumulation of Sulfonamide Resistance Genes in Arable Soils Due to Repeated Application of Manure Containing Sulfadiazine ▿

    OpenAIRE

    Heuer, Holger; Solehati, Qodiah; Zimmerling, Ute; Kleineidam, Kristina; Schloter, Michael; Müller, Tanja; Focks, Andreas; Thiele-Bruhn, Sören; Smalla, Kornelia

    2011-01-01

    Two soils were amended three times with pig manure. The abundance of sulfonamide resistance genes was determined by quantitative PCR 2 months after each application. In both soils treated with sulfadiazine-containing manure, the numbers of copies of sul1 and sul2 significantly increased compared to numbers after treatments with antibiotic-free manure or a control and accumulated with repeated applications.

  17. Generic Performance Measures. Chapter 8

    Energy Technology Data Exchange (ETDEWEB)

    Daube-Witherspoon, M. E. [Department of Radiology, University of Pennsylvania, Philadelphia, PA (United States)

    2014-12-15

    The generic nuclear medicine imager, whether a gamma camera, single photon emission computed tomography (SPECT) system or positron emission tomography (PET) scanner, comprises several main components: a detection system, a form of collimation to select γ rays at specific angles, electronics and a computing system to create the map of the radiotracer distribution. This section discusses these components in more detail. The first stage of a generic nuclear medicine imager is the detection of the γ rays emitted by the radionuclide. In the case of PET, the radiation of interest are the 511 keV annihilation photons that result from the interaction of the positron emitted by the radionuclide with an electron in the tissue. For general nuclear medicine and SPECT, there is one or sometimes more than one γ ray of interest, with energies in the range of <100 to >400 keV. The γ rays are detected when they interact and deposit energy in the crystal(s) of the imaging system. There are two main types of detector: crystals that give off light that can be converted to an electrical signal when the γ ray interacts (‘scintillators’) and semiconductors, crystals that generate an electrical signal directly when the γ ray deposits energy in the crystal. Scintillation detectors include NaI(Tl), bismuth germanate (BGO) and lutetium oxyorthosilicate (LSO); semiconductor detectors used in nuclear medicine imagers include cadmium zinc telluride (CZT). Radiation detectors are described in more detail in Chapter 6.

  18. Prioritization of generic safety issues

    International Nuclear Information System (INIS)

    Emrit, R.; Minners, W.; VanderMolen, H.

    1983-12-01

    This report presents the priority rankings for generic safety issues related to nuclear power plants. The purpose of these rankings is to assist in the timely and efficient allocation of NRC resources for the resolution of those safety issues that have a significant potential for reducing risk. The report focuses on the prioritization of generic safety issues. Issues primarily concerned with the licensing process or environmental protection and not directly related to safety have been excluded from prioritization. The prioritized issues include: TMI Action Plan items under development; previously proposed issues covered by Task Action Plans, except issues designated at Unresolved Safety Issues (USIs) which had already been assigned high priority; and newly-proposed issues. Future supplements to this report will include the prioritization of additional issues. The safety priority rankings are HIGH, MEDIUM, LOW, and DROP and have been assigned on the basis of risk significance estimates, the ratio of risk to costs and other impacts estimated to result if resolutions of the safety issues were implemented, and the consideration of uncertainties and other quantitative or qualitative factors. To the extent practical, estimates are quantitative

  19. Generic communications index: User's manual

    International Nuclear Information System (INIS)

    Dean, R.S.; Steinbrecher, D.H.; Hennick, A.

    1987-12-01

    This report is a manual for providing information required to use a special computer program developed by the NRC for indexing generic communications. The program is written in a user-friendly menu driven form using dBASE III programming language. It facilitates use of the required dBASE III search and sort capabilities to access records in a database called Generic Communications Index. This index is made up of one record each for all bulletins, circulars, and information notices, including revisions and supplements, from 1971, when such documentation started, through 1986 (or to the latest update). The program is designed for use by anyone modestly acquainted with the general use of IBM-compatible personal computers. The manual contains both a brief overview and a detailed description of the program, as well as detailed instructions for getting started using the program on a personal computer with either a two-floppy disk or a hard disk system. Included at the end are a brief description of how to handle problems which might occur, and notes on the makeup of the program and database files for help in adding records of communications for future years

  20. Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine

    DEFF Research Database (Denmark)

    Jørgensen, Kristian T; Specht, Ina O; Lenters, Virissa

    2014-01-01

    BACKGROUND: Perfluoroalkyl substances (PFAS) are suggested to affect human fecundity through longer time to pregnancy (TTP). We studied the relationship between four abundant PFAS and TTP in pregnant women from Greenland, Poland and Ukraine representing varying PFAS exposures and pregnancy planning...... behaviors. METHODS: We measured serum levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in 938 women from Greenland (448 women), Poland (203 women) and Ukraine (287 women). PFAS exposure was assessed...... weaker for women from Poland and Ukraine. PFOS, PFOA and PFHxS were not consistently associated with TTP. CONCLUSIONS: Findings do not provide consistent evidence that environmental exposure to PFAS is impairing female fecundity by delaying time taken to conceive....

  1. Perfluoroalkyl and polyfluoroalkyl substances in matched parental and cord serum in Shandong, China

    DEFF Research Database (Denmark)

    Han, Wenchao; Gao, Yu; Yao, Qian

    2018-01-01

    survey on maternal factors and risk assessment using the hazard quotients (HQs) approach based on maternal PFASs levels was conducted. Results. Within a family, the father had the highest levels of all PFASs. Among the 10 PFASs, perfluorooctanoic acid (PFOA) was the highest, with 103.38, 42.83, and 34......Background. Perfluoroalkyl and polyfluoroalkyl substances (PFASs) have been widely detected in different populations. However, limited data is available about exposure among family members. Objectives. To investigate the PFASs levels in parents and their newborns and to understand their correlation...... and health implications of in utero exposure to PFASs. Methods. Ten PFASs were measured in matched parental and cord serum (N = 369 families) from a birth cohort in Shandong, one of the regions seriously polluted by PFASs in China. The correlation of PFASs levels within families was examined. A questionnaire...

  2. Preliminary results for the detection method of perfluoroalkyl substances (PFASs residues in pork

    Directory of Open Access Journals (Sweden)

    Shih-kuo Lin

    2017-05-01

    Full Text Available The perfluoroalkyl substances (PFASs residues, which come from environmental pollution, tend to accumulate in the food chain (EFSA, 2008; Guerranti et al., 2013. 17 chemicals of PFASs family were selected for this study. Fresh pork samples were extracted by Waters® WAX SPE (solid phase extraction cartridges. All extracted samples were analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS. The results of calibration curves of each PFAS were good, the R2 values ranging from 0.9901 to 0.9993. The Recoveries were in the range 80%-119%. The protocol of extraction by Waters® WAX SPE cartridge will be applied in future studies.

  3. Skin rash during treatment with generic itraconazole.

    Science.gov (United States)

    De Vuono, Antonio; Palleria, Caterina; Scicchitano, Francesca; Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca

    2014-04-01

    Generic drugs have the same active substance, the same pharmaceutical form, the same therapeutic indications and a similar bioequivalence with the reference medicinal product (branded). Although a similar efficacy is postulated, some cases of clinical inefficacy during treatment with generic formulations have been reported. In this case, we describe a woman with onychomycosis that developed a skin rash during treatment with a generic formulation of itraconazole. Drug administration and its re-challenge confirmed the association between itraconazole and skin rash. Both Naranjo probability scale and World Health Organization causality assessment scale documented a probable association between generic-itraconazole and skin rash. The switch from generic formulation to brand one induced an improvement of symptoms. Since we are unable to evaluate the role of each excipient in the development of skin rash, we cannot rule out their involvement. However, more data are necessary to better define the similarities or differences between branded and generic formulations.

  4. Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function.

    Science.gov (United States)

    Fleisch, Abby F; Rifas-Shiman, Sheryl L; Mora, Ana M; Calafat, Antonia M; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W; Oken, Emily; Sagiv, Sharon K

    2017-03-01

    Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. We studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Children with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: -17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487; http://dx.doi.org/10.1289/EHP303.

  5. Circulating levels of perfluoroalkyl substances and prevalent diabetes in the elderly.

    Science.gov (United States)

    Lind, Lars; Zethelius, Björn; Salihovic, Samira; van Bavel, Bert; Lind, P Monica

    2014-03-01

    Several environmental contaminants, such as polychlorinated biphenyls, dioxins, bisphenol A and phthalates, have been linked to diabetes. We therefore investigated whether other kinds of contaminants, perfluoroalkyl substances (PFAS), also called perfluorinated compounds (PFCs), are also associated with diabetes. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study investigated 1,016 men and women aged 70 years. Seven PFAS were detected in almost all participant sera by ultra-high performance liquid chromatograph/tandem mass spectrometry. Diabetes was defined as use of hypoglycaemic agents or fasting glucose >7.0 mmol/l. 114 people had diabetes. In the linear analysis, no significant relationships were seen between the seven PFAS and prevalent diabetes. However, inclusion of the quadratic terms of the PFAS revealed a significant non-linear relationship between perfluorononanoic acid (PFNA) and diabetes, even after adjusting for multiple confounders (OR 1.96, 95% CI 1.19, 3.22, p = 0.008 for the linear term and OR 1.25, 95% CI 1.08, 1.44, p = 0.002 for the quadratic term). Perfluorooctanoic acid (PFOA) also showed such a relationship (p = 0.01). PFOA was related to the proinsulin/insulin ratio (a marker of insulin secretion), but none of the PFAS was related to the HOMA-IR (a marker of insulin resistance) following adjustment for multiple confounders. PFNA was related to prevalent diabetes in a non-monotonic fashion in this cross-sectional study, supporting the view that this perfluoroalkyl substance might influence glucose metabolism in humans at the level of exposure seen in the general elderly population.

  6. Bioaccumulation of perfluoroalkyl acids by earthworms (Eisenia fetida) exposed to contaminated soils.

    Science.gov (United States)

    Rich, Courtney D; Blaine, Andrea C; Hundal, Lakhwinder; Higgins, Christopher P

    2015-01-20

    The presence of perfluoroalkyl acids (PFAAs) in biosolids-amended and aqueous film-forming foam (AFFF)-impacted soils results in two potential pathways for movement of these environmental contaminants into terrestrial foodwebs. Uptake of PFAAs by earthworms (Eisenia fetida) exposed to unspiked soils with varying levels of PFAAs (a control soil, an industrially impacted biosolids-amended soil, a municipal biosolids-amended soil, and two AFFF-impacted soils) was measured. Standard 28 day exposure experiments were conducted in each soil, and measurements taken at additional time points in the municipal soil were used to model the kinetics of uptake. Uptake and elimination rates and modeling suggested that steady state bioaccumulation was reached within 28 days of exposure for all PFAAs. The highest concentrations in the earthworms were for perfluorooctane sulfonate (PFOS) in the AFFF-impacted Soil A (2160 ng/g) and perfluorododecanoate (PFDoA) in the industrially impacted soil (737 ng/g). Wet-weight (ww) and organic carbon (OC)-based biota soil accumulation factors (BSAFs) for the earthworms were calculated after 28 days of exposure for all five soils. The highest BSAF in the industrially impacted soil was for PFDoA (0.42 goc/gww,worm). Bioaccumulation factors (BAFs, dry-weight-basis, dw) were also calculated at 28 days for each of the soils. With the exception of the control soil and perfluorodecanoate (PFDA) in the industrially impacted soil, all BAF values were above unity, with the highest being for perfluorohexanesulfonate (PFHxS) in the AFFF-impacted Soil A (139 gdw,soil/gdw,worm). BSAFs and BAFs increased with increasing chain length for the perfluorocarboxylates (PFCAs) and decreased with increasing chain length for the perfluoroalkyl sulfonates (PFSAs). The results indicate that PFAA bioaccumulation into earthworms depends on soil concentrations, soil characteristics, analyte, and duration of exposure, and that accumulation into earthworms may be a potential

  7. Generic medicines and generic substitution: contrasting perspectives of stakeholders in Ireland.

    Science.gov (United States)

    O'Leary, A; Usher, C; Lynch, M; Hall, M; Hemeryk, L; Spillane, S; Gallagher, P; Barry, M

    2015-12-15

    The Health (Pricing and Supply of Medical Goods) Act 2013 passed into law in July 2013 and legislated for generic substitution in Ireland. The aim of the study was to ascertain the knowledge and perceptions of stakeholders i.e. patients, pharmacists and prescribers, of generic medicines and to generic substitution with the passing of legislation. Three stakeholder specific questionnaires were developed to assess knowledge of and perceptions to generic medicines and generic substitution. Purposive samples of patients, prescribers and pharmacists were analysed. Descriptive quantitative and qualitative analyses were undertaken. A total of 762 healthcare professionals and 353 patients were recruited. The study highlighted that over 84% of patients were familiar with generic medicines and are supportive of the concept of generic substitution. Approximately 74% of prescribers and 84% of pharmacists were supportive of generic substitution in most cases. The main areas of concern highlighted by the healthcare professionals that might impact on the successful implementation of the policy, were the issue of bioequivalence with generic medicines, the computer software systems used at present in general practitioner (GP) surgeries and the availability of branded generics. The findings from this study identify a high baseline rate of acceptance to generic medicines and generic substitution among patients, prescribers and pharmacists in the Irish setting. The concerns of the main stakeholders provide a valuable insight into the potential difficulties that may arise in its implementation, and the need for on-going reassurance and proactive dissemination of the impact of the generic substitution policy. The existing positive attitude to generic medicines and generic substitution among key stakeholders in Ireland to generic substitution, combined with appropriate support and collaboration should result in the desired increase in rates of prescribing, dispensing and use of generic

  8. Generic domain models in software engineering

    Science.gov (United States)

    Maiden, Neil

    1992-01-01

    This paper outlines three research directions related to domain-specific software development: (1) reuse of generic models for domain-specific software development; (2) empirical evidence to determine these generic models, namely elicitation of mental knowledge schema possessed by expert software developers; and (3) exploitation of generic domain models to assist modelling of specific applications. It focuses on knowledge acquisition for domain-specific software development, with emphasis on tool support for the most important phases of software development.

  9. PROBLEM OF GENERIC REPLACEMENT: ADVANTAGES AND DISADVANTAGES

    Directory of Open Access Journals (Sweden)

    S. N. Tolpygina

    2009-01-01

    Full Text Available The main differences between original and generic drugs as well as registration criteria for generics are described. Possible reasons of discrepancy in bioequivalence and therapeutic equivalence of original and generic drugs are reviewed. The examples of such a discrepancy as a result of comparative clinical trails (enalapril maleate are discussed. Approaches to planning of comparative trails on drug therapeutic equivalence are presented. 

  10. Determinants of generic drug substitution in Switzerland

    Directory of Open Access Journals (Sweden)

    Lufkin Thomas M

    2011-01-01

    Full Text Available Abstract Background Since generic drugs have the same therapeutic effect as the original formulation but at generally lower costs, their use should be more heavily promoted. However, a considerable number of barriers to their wider use have been observed in many countries. The present study examines the influence of patients, physicians and certain characteristics of the generics' market on generic substitution in Switzerland. Methods We used reimbursement claims' data submitted to a large health insurer by insured individuals living in one of Switzerland's three linguistic regions during 2003. All dispensed drugs studied here were substitutable. The outcome (use of a generic or not was modelled by logistic regression, adjusted for patients' characteristics (gender, age, treatment complexity, substitution groups and with several variables describing reimbursement incentives (deductible, co-payments and the generics' market (prices, packaging, co-branded original, number of available generics, etc.. Results The overall generics' substitution rate for 173,212 dispensed prescriptions was 31%, though this varied considerably across cantons. Poor health status (older patients, complex treatments was associated with lower generic use. Higher rates were associated with higher out-of-pocket costs, greater price differences between the original and the generic, and with the number of generics on the market, while reformulation and repackaging were associated with lower rates. The substitution rate was 13% lower among hospital physicians. The adoption of the prescribing practices of the canton with the highest substitution rate would increase substitution in other cantons to as much as 26%. Conclusions Patient health status explained a part of the reluctance to substitute an original formulation by a generic. Economic incentives were efficient, but with a moderate global effect. The huge interregional differences indicated that prescribing behaviours and

  11. Skin rash during treatment with generic itraconazole

    OpenAIRE

    De Vuono, Antonio; Palleria, Caterina; Scicchitano, Francesca; Squillace, Aida; De Sarro, Giovambattista; Gallelli, Luca

    2014-01-01

    Generic drugs have the same active substance, the same pharmaceutical form, the same therapeutic indications and a similar bioequivalence with the reference medicinal product (branded). Although a similar efficacy is postulated, some cases of clinical inefficacy during treatment with generic formulations have been reported. In this case, we describe a woman with onychomycosis that developed a skin rash during treatment with a generic formulation of itraconazole. Drug administration and its re...

  12. Sorption and biodegradation of sulfonamide antibiotics by activated sludge: experimental assessment using batch data obtained under aerobic conditions.

    Science.gov (United States)

    Yang, Sheng-Fu; Lin, Cheng-Fang; Lin, Angela Yu-Chen; Hong, Pui-Kwan Andy

    2011-05-01

    This study investigated the adsorption, desorption, and biodegradation characteristics of sulfonamide antibiotics in the presence of activated sludge with and without being subjected to NaN(3) biocide. Batch experiments were conducted and the relative contributions of adsorption and biodegradation to the observed removal of sulfonamide antibiotics were determined. Three sulfonamide antibiotics including sulfamethoxazole (SMX), sulfadimethoxine (SDM), and sulfamonomethoxine (SMM), which had been detected in the influent and the activated sludge of wastewater treatment plants (WWTP) in Taiwan, were selected for this study. Experimental results showed that the antibiotic compounds were removed via sorption and biodegradation by the activated sludge, though biodegradation was inhibited in the first 12 h possibly due to competitive inhibition of xenobiotic oxidation by readily biodegradable substances. The affinity of sulfonamides to sterilized sludge was in the order of SDM > SMM > SMX. The sulfonamides existed predominantly as anions at the study pH of 6.8, which resulted in a low level of adsorption to the activated sludge. The adsorption/desorption isotherms were of a linear form, as well described by the Freundlich isotherm with the n value approximating unity. The linear distribution coefficients (K(d)) were determined from batch equilibrium experiments with values of 28.6 ± 1.9, 55.7 ± 2.2, and 110.0 ± 4.6 mL/g for SMX, SMM, and SDM, respectively. SMX, SMM, and SDM desorb reversibly from the activated sludge leaving behind on the solids 0.9%, 1.6%, and 5.2% of the original sorption dose of 100 μg/L. The sorbed antibiotics can be introduced into the environment if no further treatments were employed to remove them from the biomass. Copyright © 2011 Elsevier Ltd. All rights reserved.

  13. Transport of perfluoroalkyl acids in a water-saturated sediment column investigated under near-natural conditions

    International Nuclear Information System (INIS)

    Vierke, Lena; Möller, Axel; Klitzke, Sondra

    2014-01-01

    The aim of this study was to gain an understanding of the transport of C 4–10 perfluoroalkyl carboxylic acids (PFCAs) and C 4,6,8 perfluoroalkyl sulfonic acids (PFSAs) in a water-saturated sediment column representing a riverbank filtration scenario under near-natural conditions. Short-chain PFCAs and PFSAs with up to six C-atoms showed complete tracer-like breakthrough. Longer chain ones were retarded due to sorption to the sediment or due to other processes in the aqueous phase. The study reports the first column derived sediment–water partition coefficients ranging from 0.01 cm 3 g −1 to 0.41 cm 3 g −1 for C 4,6 PFSAs and from 0.0 cm 3 g −1 to 6.5 cm 3 g −1 for C 4,5,6,8,9 PFCAs. The results clearly indicate that short-chain PFCAs and PFSAs may pose a problem if contaminated surface waters are used for drinking water production via riverbank filtration. Highlights: • Transport of per- and polyfluorinated compounds in a riverbank filtration scenario. • Investigations under near-natural conditions with a water-saturated sediment column. • Processes in water and sediment control the transport of analytes. • Short chain PFCAs and PFSAs are not retarded in the water-saturated sediment column. • First column derived sediment–water partition coefficients. -- Quantification of breakthrough of perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) under conditions simulating a riverbank filtration scenario

  14. Determinants and Temporal Trends of Perfluoroalkyl Substances in Pregnant Women: The Hokkaido Study on Environment and Children’s Health

    OpenAIRE

    Meng-Shan Tsai; Chihiro Miyashita; Atsuko Araki; Sachiko Itoh; Yu Ait Bamai; Houman Goudarzi; Emiko Okada; Ikuko Kashino; Hideyuki Matsuura; Reiko Kishi

    2018-01-01

    Perfluoroalkyl substances (PFAS) are persistent bio-accumulative chemicals that impact the health of pregnant women and their children. PFAS derive from environmental and consumer products, which depend on human lifestyle, socioeconomic characteristics, and time variation. Here, we aimed to explore the temporal trends of PFAS in pregnant women and the characteristics related to maternal PFAS concentration. Our study is part of the Hokkaido Study on Environment and Children’s Health, the Hokka...

  15. Generic Hurricane Extreme Seas State

    DEFF Research Database (Denmark)

    Wehmeyer, Christof; Skourup, Jesper; Frigaard, Peter

    2012-01-01

    Extreme sea states, which the IEC 61400-3 (2008) standard requires for the ultimate limit state (ULS) analysis of offshore wind turbines are derived to establish the design basis for the conceptual layout of deep water floating offshore wind turbine foundations in hurricane affected areas....... Especially in the initial phase of floating foundation concept development, site specific metocean data are usually not available. As the areas of interest are furthermore not covered by any design standard, in terms of design sea states, generic and in engineering terms applicable environmental background...... data is required for a type specific conceptual design. ULS conditions for different return periods are developed, which can subsequently be applied in siteindependent analysis and conceptual design. Recordings provided by National Oceanic and Atmospheric Administration (NOAA), of hurricanes along...

  16. 76 FR 57767 - Proposed Generic Communication; Draft NRC Generic Letter 2011-XX: Seismic Risk Evaluations for...

    Science.gov (United States)

    2011-09-16

    ... NUCLEAR REGULATORY COMMISSION [NRC-2011-0204] Proposed Generic Communication; Draft NRC Generic Letter 2011-XX: Seismic Risk Evaluations for Operating Reactors AGENCY: Nuclear Regulatory Commission... FR 54507), that requested public comment on Draft NRC Generic Letter 2011- XX: Seismic Risk...

  17. Role of the sulfonamide moiety of Ru(II) half-sandwich complexes in the asymmetric transfer hydrogenation of 3,4-dihydroisoquinolines

    Czech Academy of Sciences Publication Activity Database

    Matuška, O.; Zápal, J.; Hrdličková, R.; Mikoška, M.; Pecháček, J.; Vilhanová, B.; Václavík, Jiří; Kuzma, M.; Kačer, P.

    2016-01-01

    Roč. 118, č. 1 (2016), s. 215-222 ISSN 1878-5190 Institutional support: RVO:61388963 Keywords : ruthenium * asymmetric transfer hydrogenation * dihydroisoquinolines * sulfonamide Subject RIV: CC - Organic Chemistry Impact factor: 1.264, year: 2016

  18. Ionic treatment for removal of sulfonamide and tetracycline classes of antibiotic

    International Nuclear Information System (INIS)

    Choi, Keun-Joo; Son, Hee-Jong; Kim, Seung-Hyun

    2007-01-01

    Self-decomposition and removal of antibiotics by ionic treatment was evaluated in this study. Seven sulfonamide classes (SA) and seven tetracycline classes (TA) of antibiotic were selected for this purpose. According to this study, self-decomposition of SAs and TAs was slow, and a considerable amount of antibiotics still remained after 15 days. Ionic treatment was effective for removal of SAs and TAs, but organic interference was observed. When dissolved organic (DOC) was present in raw water, the removal performance of antibiotics generally deteriorated due to competition with organics. SAs and TAs, which were present in ionic form at neutral pH, were removed through ion exchange. Their removal efficiencies were closely related to their chemical structure. Antibiotics with stronger electronegativity were easier to remove by ionic treatment. Equilibrium equations for removal of SAs and TAs by ionic treatment were also presented

  19. Recent advances in sample preparation techniques and methods of sulfonamides detection - A review.

    Science.gov (United States)

    Dmitrienko, Stanislava G; Kochuk, Elena V; Apyari, Vladimir V; Tolmacheva, Veronika V; Zolotov, Yury A

    2014-11-19

    Sulfonamides (SAs) have been the most widely used antimicrobial drugs for more than 70 years, and their residues in foodstuffs and environmental samples pose serious health hazards. For this reason, sensitive and specific methods for the quantification of these compounds in numerous matrices have been developed. This review intends to provide an updated overview of the recent trends over the past five years in sample preparation techniques and methods for detecting SAs. Examples of the sample preparation techniques, including liquid-liquid and solid-phase extraction, dispersive liquid-liquid microextraction and QuEChERS, are given. Different methods of detecting the SAs present in food and feed and in environmental, pharmaceutical and biological samples are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Synthesis and in silico studies of novel sulfonamides having oxadiazole ring: As β-glucuronidase inhibitors.

    Science.gov (United States)

    Taha, Muhammad; Baharudin, Mohd Syukri; Ismail, Nor Hadiani; Selvaraj, Manikandan; Salar, Uzma; Alkadi, Khaled A A; Khan, Khalid Mohammed

    2017-04-01

    Novel sulfonamides having oxadiazole ring were synthesized by multistep reaction and evaluated to check in vitro β-glucuronidase inhibitory activity. Luckily, except compound 13, all compounds were found to demonstrate good inhibitory activity in the range of IC 50 =2.40±0.01-58.06±1.60μM when compared to the standard d-saccharic acid 1,4-lactone (IC 50 =48.4±1.25μM). Structure activity relationship was also presented. However, in order to ensure the SAR as well as the molecular interactions of compounds with the active site of enzyme, molecular docking studies on most active compounds 19, 16, 4 and 6 was carried out. All derivatives were fully characterized by 1 H NMR, 13 C NMR and EI-MS spectroscopic techniques. CHN analysis was also presented. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Insights into functional-group-tolerant polymerization catalysis with phosphine-sulfonamide palladium (II) complexes

    KAUST Repository

    Jian, Zhongbao

    2014-12-08

    Two series of cationic palladium(II) methyl complexes {[(2-MeOC6H4)2PC6H4SO2NHC6H3(2,6-R1,R2)]PdMe}2[A]2 (X1+-A: R1=R2=H: H1+-A; R1=R2=CH(CH3)2: DIPP1+-A; R1=H, R2=CF3: CF31+-A; A=BF4 or SbF6) and neutral palladium(II) methyl complexes {[(2-MeOC6H4)2PC6H4SO2NC6H3(2,6-R1,R2)]PdMe(L)} (X1-acetone: L=acetone; X1-dmso: L=dimethyl sulfoxide; X1-pyr: L=pyridine) chelated by a phosphine-sulfonamide were synthesized and fully characterized. Stoichiometric insertion of methyl acrylate (MA) into all complexes revealed that a 2,1 regiochemistry dominates in the first insertion of MA. Subsequently, for the cationic complexes X1+-A, β-H elimination from the 2,1-insertion product X2+-AMA-2,1 is overwhelmingly favored over a second MA insertion to yield two major products X4+-AMA-1,2 and X5+-AMA. By contrast, for the weakly coordinated neutral complexes X1-acetone and X1-dmso, a second MA insertion of the 2,1-insertion product X2MA-2,1 is faster than β-H elimination and gives X3MA as major products. For the strongly coordinated neutral complexes X1-pyr, no second MA insertion and no β-H elimination (except for DIPP2-pyrMA-2,1) were observed for the 2,1-insertion product X2-pyrMA-2,1. The cationic complexes X1+-A exhibited high catalytic activities for ethylene dimerization, affording butenes (C4) with a high selectivity of up to 97.7% (1-butene: 99.3%). Differences in activities and selectivities suggest that the phosphine-sulfonamide ligands remain coordinated to the metal center in a bidentate fashion in the catalytically active species. By comparison, the neutral complexes X1-acetone, X1-dmso, and X1-pyr showed very low activity towards ethylene to give traces of oligomers. DFT analyses taking into account the two possible coordination modes (O or N) of the sulfonamide ligand for the cationic system CF31+ suggested that the experimentally observed high activity in ethylene dimerization is the result of a facile first ethylene insertion into the O-coordinated PdMe isomer and

  2. Synthesis and Antimicrobial Activity of Bis-4,6-sulfonamidated 5,7-Dinitrobenzofuroxans

    Directory of Open Access Journals (Sweden)

    Irina V. Galkina

    2014-01-01

    Full Text Available A new series of bis-4,6-sulfonamidated 5,7-dinitrbenzofuroxans  7–11 had been synthesized and tested for antimicrobial activity. The structures of new sulfanilamide derivatives were characterized by elemental analysis, IR spectroscopy, and mass spectrometry (MALDITOF. The synthesized compounds were tested for their in vitro antimicrobial activity using the disk diffusion method against Gram-positive bacteria Staphylococcus aureus; the Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis; the fungal strain Aspergillus niger; and the yeast-like pathogenic fungus Candida albicans. Our results indicate that the compounds 7–11 exhibit potent antimicrobial activity. The stability of the compounds was evaluated by TG and DSC methods.

  3. A Generic Approach to Parameter Control

    NARCIS (Netherlands)

    Karafotias, G.; Smit, S.K.; Eiben, A.E.

    2012-01-01

    On-line control of EA parameters is an approach to parameter setting that offers the advantage of values changing during the run. In this paper, we investigate parameter control from a generic and parameter-independent perspective. We propose a generic control mechanism that is targeted to

  4. Once more the generic name Passerina Vieillot

    NARCIS (Netherlands)

    Oort, van E.D.

    1910-01-01

    The note on the generic name of the Snow-bunting by Dr. E. Hartert in this part of our periodical gives me cause to revert to the subject of my note on the generic name Passerina Vieillot and to state here, that I stand to what I have said about the rejection of this name in Zoology (Notes Leyden

  5. HTGR generic technology program plan (FY 80)

    International Nuclear Information System (INIS)

    1980-01-01

    Purpose of the program is to develop base technology and to perform design and development common to the HTGR Steam Cycle, Gas Turbine, and Process Heat Plants. The generic technology program breaks into the base technology, generic component, pebble-bed study, technology transfer, and fresh fuel programs

  6. South African patient's acceptance of generic drugs

    African Journals Online (AJOL)

    mechanism in this regard for final consumers, insurance providers, and ... facilities are viewed as inferior, treated with sus- picion and ... to choose a generic drug if the decision was supported by their doctor ... The effect of brand to generic and ...

  7. Synthesis, Pharmacological Profile and Docking Studies of New Sulfonamides Designed as Phosphodiesterase-4 Inhibitors.

    Directory of Open Access Journals (Sweden)

    Isabelle Karine da Costa Nunes

    Full Text Available Prior investigations showed that increased levels of cyclic AMP down-regulate lung inflammatory changes, stimulating the interest in phosphodiesterase (PDE4 as therapeutic target. Here, we described the synthesis, pharmacological profile and docking properties of a novel sulfonamide series (5 and 6a-k designed as PDE4 inhibitors. Compounds were screened for their selectivity against the four isoforms of human PDE4 using an IMAP fluorescence polarized protocol. The effect on allergen- or LPS-induced lung inflammation and airway hyper-reactivity (AHR was studied in A/J mice, while the xylazine/ketamine-induced anesthesia test was employed as a behavioral correlate of emesis in rodents. As compared to rolipram, the most promising screened compound, 6a (LASSBio-448 presented a better inhibitory index concerning PDE4D/PDE4A or PDE4D/PDE4B. Accordingly, docking analyses of the putative interactions of LASSBio-448 revealed similar poses in the active site of PDE4A and PDE4C, but slight unlike orientations in PDE4B and PDE4D. LASSBio-448 (100 mg/kg, oral, 1 h before provocation, inhibited allergen-induced eosinophil accumulation in BAL fluid and lung tissue samples. Under an interventional approach, LASSBio-448 reversed ongoing lung eosinophilic infiltration, mucus exacerbation, peribronchiolar fibrosis and AHR by allergen provocation, in a mechanism clearly associated with blockade of pro-inflammatory mediators such as IL-4, IL-5, IL-13 and eotaxin-2. LASSBio-448 (2.5 and 10 mg/kg also prevented inflammation and AHR induced by LPS. Finally, the sulfonamide derivative was shown to be less pro-emetic than rolipram and cilomilast in the assay employed. These findings suggest that LASSBio-448 is a new PDE4 inhibitor with marked potential to prevent and reverse pivotal pathological features of diseases characterized by lung inflammation, such as asthma.

  8. Electrochemical degradation of sulfonamides at BDD electrode: Kinetics, reaction pathway and eco-toxicity evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Fabiańska, Aleksandra; Białk-Bielińska, Anna; Stepnowski, Piotr [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland); Stolte, Stefan [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland); UFT-Centre of Environmental Research and Sustainable Technology, University of Bremen, Leobener Straße UFT, D-28359 Bremen (Germany); Siedlecka, Ewa Maria, E-mail: ewa.siedlecka@ug.edu.pl [Faculty of Chemistry, University of Gdansk, ul. Wita Stwosza 63, 80-952 Gdansk (Poland)

    2014-09-15

    Highlights: • SNs were electrochemically oxidized at BDD in one compartment reactor. • The efficiency of SN degradation was the highest in effluents from municipal WWTP. • The electro-degradation SNs based on oxidation but reduction was also possible. • Electrochemical oxidation of SNs led in some cases to mixtures toxic to L. minor. - Abstract: The investigation dealt with electrochemical oxidation of five sulfonamides (SNs): sulfadiazine (SDZ), sulfathiazole (STZ), sulfamerazine (SMR), sulfamethazine (SMN) and sulfadimethoxine (SDM) in aqueous solution at boron-doped diamond (BDD) electrode. All studied sulfonamides were degraded according to a pseudo first order kinetics. The structure of SNs had no significant effect on the values of pseudo first order rate constants. Increased degradation efficiency was observed in higher temperature and in acidic pH. Due to the presence of chlorine and nitrate SNs were more effectively oxidized from municipal wastewater treatment plant (WWTP) effluents than from pure supporting electrolyte Na{sub 2}SO{sub 4}. The intermediates identified by LC–MS and GC–MS analysis suggested that the hydroxyl radicals attack mainly the S-N bond, but also the aromatic ring systems (aniline, pyrimidine or triazole) of SNs. Finally, the toxicity of the SNs solutions and effluents after electrochemical treatment was assessed through the measurement of growth inhibition of green algae (Scenedesmus vacualatus) and duckweed (Lemna minor). Toxicity of SMR, STZ, SMN solutions before and after electrochemical oxidation and SDM solution after the process in L. minor test was observed. No significant toxicity of studied SNs was observed in algae test.

  9. Electrochemical degradation of sulfonamides at BDD electrode: Kinetics, reaction pathway and eco-toxicity evaluation

    International Nuclear Information System (INIS)

    Fabiańska, Aleksandra; Białk-Bielińska, Anna; Stepnowski, Piotr; Stolte, Stefan; Siedlecka, Ewa Maria

    2014-01-01

    Highlights: • SNs were electrochemically oxidized at BDD in one compartment reactor. • The efficiency of SN degradation was the highest in effluents from municipal WWTP. • The electro-degradation SNs based on oxidation but reduction was also possible. • Electrochemical oxidation of SNs led in some cases to mixtures toxic to L. minor. - Abstract: The investigation dealt with electrochemical oxidation of five sulfonamides (SNs): sulfadiazine (SDZ), sulfathiazole (STZ), sulfamerazine (SMR), sulfamethazine (SMN) and sulfadimethoxine (SDM) in aqueous solution at boron-doped diamond (BDD) electrode. All studied sulfonamides were degraded according to a pseudo first order kinetics. The structure of SNs had no significant effect on the values of pseudo first order rate constants. Increased degradation efficiency was observed in higher temperature and in acidic pH. Due to the presence of chlorine and nitrate SNs were more effectively oxidized from municipal wastewater treatment plant (WWTP) effluents than from pure supporting electrolyte Na 2 SO 4 . The intermediates identified by LC–MS and GC–MS analysis suggested that the hydroxyl radicals attack mainly the S-N bond, but also the aromatic ring systems (aniline, pyrimidine or triazole) of SNs. Finally, the toxicity of the SNs solutions and effluents after electrochemical treatment was assessed through the measurement of growth inhibition of green algae (Scenedesmus vacualatus) and duckweed (Lemna minor). Toxicity of SMR, STZ, SMN solutions before and after electrochemical oxidation and SDM solution after the process in L. minor test was observed. No significant toxicity of studied SNs was observed in algae test

  10. Brand vs generic adverse event reporting patterns: An authorized generic-controlled evaluation of cardiovascular medications.

    Science.gov (United States)

    Alatawi, Y; Rahman, Md M; Cheng, N; Qian, J; Peissig, P L; Berg, R L; Page, C D; Hansen, R A

    2018-06-01

    Some public scepticism exists about generics in terms of whether brand and generic drugs produce identical outcomes. This study explores whether adverse event (AE) reporting patterns are similar between brand and generic drugs, using authorized generics (AGs) as a control for possible generic drug perception biases. Events reported to the FDA Adverse Event Reporting System from the years 2004-2015 were analysed. Drugs were classified as brand, AG or generic based on drug and manufacturer names. Reports were included if amlodipine, losartan, metoprolol extended release (ER) or simvastatin were listed as primary or secondary suspect drugs. Disproportionality analyses using the reporting odds ratio (ROR) assessed the relative rate of reporting labelled AEs compared to reporting these AEs with all other drugs. The Breslow-Day test compared RORs across brand, AG and generic. Interrupted time series analysis evaluated the impact of generic entry on reporting trends. Generics accounted for significant percentages of total U.S. reports, but AGs accounted for smaller percentages of reports, including for amlodipine (14.26%), losartan (1.48%), metoprolol ER (0.35%) and simvastatin (0.70%). Whereas the RORs were significantly different for multiple brand vs generic comparisons, the AG vs generic comparisons yielded fewer statistically significant findings. Namely, only the ROR for AG differed from generic for amlodipine with peripheral oedema (P brand and generic compared with AG and generic. Use of AGs as a control for perception biases against generics is useful, but this approach can be limited by small AG report numbers. Requiring the manufacturer name to be printed on the prescription bottle or packaging could improve the accuracy of assignment for products being reported. © 2017 John Wiley & Sons Ltd.

  11. Rapid trace level determination of sulfonamide residues in honey with online extraction using short C-18 column by high-performance liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Sajid, Muhammad; Na, Na; Safdar, Muhammad; Lu, Xin; Ma, Lin; He, Lan; Ouyang, Jin

    2013-11-01

    A sensitive and inexpensive quantification method with online extraction using a short C-18 column for sulfonamide residues in honey by high performance liquid chromatography with fluorescence detector was developed and validated. In sample preparation, acid hydrolysis was used to break the N-glycoside bond between the honey sugar and sulfonamide drugs and derivatization of sulfonamide residues with fluorescamine was conducted at pH 3.5 using a citrate buffer (0.5M) in the honey matrix. The chromatography was carried out on Zorbax Extended C-18 (250mm×4.6mm; 5μm) column, using a mixture of acetonitrile and an acetate buffer (pH 4.50, 20mM) as a mobile phase. A Zorbax Extended C-18 (12mm×4.6mm; 5μm) column was used for online extraction of fifteen sulfonamide residues from honey sample with the help of a two position valve. The limit of quantification of sulfonamide residues in honey was less than 3ngg(-1), and the percentage recovery of study compounds in spiked honey sample was from 80% for sulfacetamide to 100% of sulfachloropyridazine. The developed method has excellent linearity for all studied sulfonamides with a correlation coefficient 0.993. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. [Generic drugs: good or bad? Physician's knowledge of generic drugs and prescribing habits].

    Science.gov (United States)

    García, A J; Martos, F; Leiva, F; Sánchez de la Cuesta, F

    2003-01-01

    In this article we analyze the responses of 1220 Spanish physicians who participated in a survery about generic drugs. A previously validated questionnaire was sent to physicians through the Spanish Medical Councils of the different provinces. Four items were analyzed: what doctors know about generic drugs (knowledge); physicians' prescribing habits concerning these drugs (attitude and professional competence); how prescription of generic drugs effects pharmaceutical costs amd, finally, what doctors believe a generic drug should be. The influence of physician-related variables (age, type of contract, specialty, workload, etc.) on prescribing of generic drugs was also analyzed. In view of the results, we believe that to rationalize expenditure through and appropriate policy on generic drugs Spanish health authorities should offer more and better training and information (clear and independent) about what generic drugs are.

  13. Design and synthesis of novel sulfonamide-containing bradykinin hB2 receptor antagonists. 1. Synthesis and SAR of alpha,alpha-dimethylglycine sulfonamides.

    Science.gov (United States)

    Fattori, Daniela; Rossi, Cristina; Fincham, Christopher I; Berettoni, Marco; Calvani, Federico; Catrambone, Fernando; Felicetti, Patrizia; Gensini, Martina; Terracciano, Rosa; Altamura, Maria; Bressan, Alessandro; Giuliani, Sandro; Maggi, Carlo A; Meini, Stefania; Valenti, Claudio; Quartara, Laura

    2006-06-15

    We recently published the extensive in vivo pharmacological characterization of MEN 16132 (J. Pharmacol. Exp. Ther. 2005, 616-623; Eur. J. Pharmacol. 2005, 528, 7), a member of the sulfonamide-containing human B(2) receptor (hB(2)R) antagonists. Here we report, in detail, how this family of compounds was designed, synthesized, and optimized to provide a group of products with subnanomolar affinity for the hB(2)R and high in vivo potency after topical administration to the respiratory tract. The series was designed on the basis of indications from the X-ray structures of the key structural motifs A and B present in known antagonists and is characterized by the presence of an alpha,alpha-dialkyl amino acid. The first lead (17) of the series was submitted to extensive chemical work to elucidate the structural requirements to increase hB(2) receptor affinity and antagonist potency in bioassays expressing the human B(2) receptor (hB(2)R). The following structural features were selected: a 2,4-dimethylquinoline moiety and a piperazine linker acylated with a basic amino acid. The representative lead compound 68 inhibited the specific binding of [(3)H]BK to hB(2)R with a pKi of 9.4 and antagonized the BK-induced inositolphosphate (IP) accumulation in recombinant cell systems expressing the hB(2)R with a pA(2) of 9.1. Moreover, compound 68 when administered (300 nmol/kg) intratracheally in the anesthetized guinea pig, was able to significantly inhibit BK-induced bronchoconstriction for up to 120 min after its administration, while having a lower and shorter lasting effect on hypotension.

  14. Generic Local Hamiltonians are Gapless

    Science.gov (United States)

    Movassagh, Ramis

    2017-12-01

    We prove that generic quantum local Hamiltonians are gapless. In fact, we prove that there is a continuous density of states above the ground state. The Hamiltonian can be on a lattice in any spatial dimension or on a graph with a bounded maximum vertex degree. The type of interactions allowed for include translational invariance in a disorder (i.e., probabilistic) sense with some assumptions on the local distributions. Examples include many-body localization and random spin models. We calculate the scaling of the gap with the system's size when the local terms are distributed according to a Gaussian β orthogonal random matrix ensemble. As a corollary, there exist finite size partitions with respect to which the ground state is arbitrarily close to a product state. When the local eigenvalue distribution is discrete, in addition to the lack of an energy gap in the limit, we prove that the ground state has finite size degeneracies. The proofs are simple and constructive. This work excludes the important class of truly translationally invariant Hamiltonians where the local terms are all equal.

  15. Generic physical protection logic trees

    International Nuclear Information System (INIS)

    Paulus, W.K.

    1981-10-01

    Generic physical protection logic trees, designed for application to nuclear facilities and materials, are presented together with a method of qualitative evaluation of the trees for design and analysis of physical protection systems. One or more defense zones are defined where adversaries interact with the physical protection system. Logic trees that are needed to describe the possible scenarios within a defense zone are selected. Elements of a postulated or existing physical protection system are tagged to the primary events of the logic tree. The likelihood of adversary success in overcoming these elements is evaluated on a binary, yes/no basis. The effect of these evaluations is propagated through the logic of each tree to determine whether the adversary is likely to accomplish the end event of the tree. The physical protection system must be highly likely to overcome the adversary before he accomplishes his objective. The evaluation must be conducted for all significant states of the site. Deficiencies uncovered become inputs to redesign and further analysis, closing the loop on the design/analysis cycle

  16. Generic physical protection logic trees

    Energy Technology Data Exchange (ETDEWEB)

    Paulus, W.K.

    1981-10-01

    Generic physical protection logic trees, designed for application to nuclear facilities and materials, are presented together with a method of qualitative evaluation of the trees for design and analysis of physical protection systems. One or more defense zones are defined where adversaries interact with the physical protection system. Logic trees that are needed to describe the possible scenarios within a defense zone are selected. Elements of a postulated or existing physical protection system are tagged to the primary events of the logic tree. The likelihood of adversary success in overcoming these elements is evaluated on a binary, yes/no basis. The effect of these evaluations is propagated through the logic of each tree to determine whether the adversary is likely to accomplish the end event of the tree. The physical protection system must be highly likely to overcome the adversary before he accomplishes his objective. The evaluation must be conducted for all significant states of the site. Deficiencies uncovered become inputs to redesign and further analysis, closing the loop on the design/analysis cycle.

  17. Generic theory for channel sinuosity.

    Science.gov (United States)

    Lazarus, Eli D; Constantine, José Antonio

    2013-05-21

    Sinuous patterns traced by fluid flows are a ubiquitous feature of physical landscapes on Earth, Mars, the volcanic floodplains of the Moon and Venus, and other planetary bodies. Typically discussed as a consequence of migration processes in meandering rivers, sinuosity is also expressed in channel types that show little or no indication of meandering. Sinuosity is sometimes described as "inherited" from a preexisting morphology, which still does not explain where the inherited sinuosity came from. For a phenomenon so universal as sinuosity, existing models of channelized flows do not explain the occurrence of sinuosity in the full variety of settings in which it manifests, or how sinuosity may originate. Here we present a generic theory for sinuous flow patterns in landscapes. Using observations from nature and a numerical model of flow routing, we propose that flow resistance (representing landscape roughness attributable to topography or vegetation density) relative to surface slope exerts a fundamental control on channel sinuosity that is effectively independent of internal flow dynamics. Resistance-dominated surfaces produce channels with higher sinuosity than those of slope-dominated surfaces because increased resistance impedes downslope flow. Not limited to rivers, the hypothesis we explore pertains to sinuosity as a geomorphic pattern. The explanation we propose is inclusive enough to account for a wide variety of sinuous channel types in nature, and can serve as an analytical tool for determining the sinuosity a landscape might support.

  18. Generic adversary characteristics: summary report

    International Nuclear Information System (INIS)

    Stewart, J.B. Jr.; Davidson, J.J.; Jones, H.B.; Fulwiler, C.H.; Mullen, S.A.

    1978-07-01

    The adversaries studied were found to be complex, often unpredictable, and dynamic. The adversary typically goes through a complex decision-making process between the time a potential target is identified and the moment the decision to act is made. This study analyzes the adversary characteristics, and the following conclusions are made: one of the least likely methods of attack is an overt armed assault. Terrorists and psychotics depend upon a high degree of personal dedication. No single generic adversary group or individual exhibits strength in every characteristic. Physical danger appears to have some deterrent effect on all adversaries except the psychotics. Organized and professional criminals often try to recruit insiders. Disoriented persons, white-collar criminals, and disgruntled employees tend to operate as insiders. Professional criminals, many terrorist groups, some extremist protest groups, and certain disoriented persons plan carefully before initiating a criminal mission. Organized crime and miscellaneous criminal adversaries rely on deception and ruse to bypass security. After the decision to commit a crime, the resources deployed by terrorists or organized criminals will be a function of their perception of the operational requirements of the crime. The nature of ''threat'' is dynamic; adversary behavior and capability appear to be related to prevailing political, economic, and social conditions

  19. 78 FR 22553 - Generic Drug Facilities, Sites, and Organizations

    Science.gov (United States)

    2013-04-16

    ...] Generic Drug Facilities, Sites, and Organizations AGENCY: Food and Drug Administration, HHS. ACTION.... Generic drug facilities, certain sites, and organizations identified in a generic drug submission are... active pharmaceutical ingredients and certain other sites and organizations that support the manufacture...

  20. 78 FR 59911 - Generic Information Collection for Land Management Planning

    Science.gov (United States)

    2013-09-30

    ... DEPARTMENT OF AGRICULTURE Forest Service Generic Information Collection for Land Management... organizations on the proposed information collection, Generic Information Collection for Land Management... related to forest management. The intent of this generic information collection request (ICR) is to...

  1. Genotoxic, Cytotoxic, Antigenotoxic, and Anticytotoxic Effects of Sulfonamide Chalcone Using the Ames Test and the Mouse Bone Marrow Micronucleus Test.

    Directory of Open Access Journals (Sweden)

    Carolina Ribeiro E Silva

    Full Text Available Chalcones present several biological activities and sulfonamide chalcone derivatives have shown important biological applications, including antitumor activity. In this study, genotoxic, cytotoxic, antigenotoxic, and anticytotoxic activities of the sulfonamide chalcone N-{4-[3-(4-nitrophenylprop-2-enoyl]phenyl} benzenesulfonamide (CPN were assessed using the Salmonella typhimurium reverse mutation test (Ames test and the mouse bone marrow micronucleus test. The results showed that CPN caused a small increase in the number of histidine revertant colonies in S. typhimurium strains TA98 and TA100, but not statistically significant (p > 0.05. The antimutagenicity test showed that CPN significantly decreased the number of His+ revertants in strain TA98 at all doses tested (p 0.05. Additionally, CPN co-administered with MMC significantly increased PCE/NCE ratio at all doses tested, demonstrating its anticytotoxic effect. In summary, CPN presented genotoxic, cytotoxic, antigenotoxic, and anticytotoxic properties.

  2. Inhibition of the α-carbonic anhydrase from Vibrio cholerae with amides and sulfonamides incorporating imidazole moieties.

    Science.gov (United States)

    De Vita, Daniela; Angeli, Andrea; Pandolfi, Fabiana; Bortolami, Martina; Costi, Roberta; Di Santo, Roberto; Suffredini, Elisabetta; Ceruso, Mariangela; Del Prete, Sonia; Capasso, Clemente; Scipione, Luigi; Supuran, Claudiu T

    2017-12-01

    We discovered novel and selective sulfonamides/amides acting as inhibitors of the α-carbonic anhydrase (CA, EC 4.2.1.1) from the pathogenic bacterium Vibrio cholerae (VchCA). This Gram-negative bacterium is the causative agent of cholera and colonises the upper small intestine where sodium bicarbonate is present at a high concentration. The secondary sulfonamides and amides investigated here were potent, low nanomolar VchCA inhibitors whereas their inhibition of the human cytosolic isoforms CA I and II was in the micromolar range or higher. The molecules represent an interesting lead for antibacterial agents with a possibly new mechanism of action, although their CA inhibition mechanism is unknown for the moment.

  3. A multicenter experience with generic tacrolimus conversion.

    Science.gov (United States)

    McDevitt-Potter, Lisa M; Sadaka, Basma; Tichy, Eric M; Rogers, Christin C; Gabardi, Steven

    2011-09-27

    The first generic tacrolimus product gained Food and Drug Administration approval in August 2009. This prospective, observational trial sought to determine the need for dose titrations and measure drug cost savings on conversion to generic tacrolimus. Transplant recipients on stable tacrolimus doses were converted from brand to generic tacrolimus on a mg:mg basis. Data were collected at the time of generic conversion (study arm) and at a time point exactly 6 months before conversion (control arm) for all subjects. Seventy conversions from four centers are reported. Subjects were a mean of 70 months after kidney (n=37), liver (n=28), or multiorgan (n=5) transplant. In the study arm, mean tacrolimus doses were 4.4 and 4.5 mg/d and mean tacrolimus trough concentrations were 5.8 and 5.9 ng/mL before and after conversion, respectively. In the control arm, mean tacrolimus doses were 4.6 and 4.6 mg/d and mean tacrolimus trough concentrations were 6.1 and 5.9 ng/mL before and after the control time point, respectively. Dose titrations occurred in five patients (7%) in the control arm and 15 patients (21%) in the study arm (P=0.028). Mean monthly drug costs were $645 for brand, $593 for generic, and $595 for generic after dose titrations. Mean monthly patient copays were $38 for brand and $15 for generic. These cumulative data show that dose requirements and trough levels are similar between brand and generic tacrolimus and that generic substitution allows for savings. However, postconversion monitoring is prudent as patients may require dose titration.

  4. Analysis of perfluoroalkyl substances in cord blood by turbulent flow chromatography coupled to tandem mass spectrometry

    International Nuclear Information System (INIS)

    Llorca, Marta; Pérez, Francisca; Farré, Marinella; Agramunt, Sílvia; Kogevinas, Manolis; Barceló, Damià

    2012-01-01

    A fast on-line analytical method based on turbulent flow chromatography (TFC) in combination with tandem mass spectrometry has been applied for the first time for the analysis of eighteen perfluoroalkyl substances (PFASs), in cord blood. A simple and rapid sample pre-treatment was optimised consisting on protein precipitation of 100 μL of sample with acetonitrile (1:1) followed by centrifugation during 10 min. The method was adapted to be sensitive enough and robust with minimum sample injection volume requirements (20 μL). The optimised methodology presented method limits of detection (MLOD) between 0.031 and 0.76 μg/L, detection capabilities (CCα) in the range between 0.005 and 0.99 μg/L and decision limits (CCβ) ranging from 0.006 to 1.16 μg/L. The recoveries in blank blood were calculated by spiking experiments with a mixture of 18 PFASs and established between 70 and 126% for most of compounds. Isotopic dilution was carried out for quantification of selected analytes. In-house validation of this new approach was carried out according to the requirements in the 2002/657/EC Decision. Finally the good applicability of this new approach was proved by the analysis of 60 cord blood samples from two different Mediterranean cities, Barcelona (Spain) and Heraklion (Greece). Ions perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) were found at highest concentration and the more frequently compounds were PFHxS, PFOS and perfluorooctanoic acid (PFOA). The newly developed method proved to be suitable for large-scale epidemiologic studies, and to the data on PFASs exposure during pregnancy. -- Highlights: ► An on-line method has been developed for the analysis of 18 perfluoroalkyl substances. ► The method is based on turbulent flow chromatography tandem mass spectrometry. ► The method was applied in 60 cord blood samples from 2 Mediterranean cities. ► Acidic compounds were more frequently found and the method was proved to be suitable for

  5. Analysis of perfluoroalkyl substances in cord blood by turbulent flow chromatography coupled to tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Llorca, Marta; Perez, Francisca [Department of Environmental Chemistry, IDAEA-CSIC, Barcelona (Spain); Farre, Marinella, E-mail: mfuqam@cid.csic.es [Department of Environmental Chemistry, IDAEA-CSIC, Barcelona (Spain); Agramunt, Silvia [Centre for Research in Environmental Epidemiology (CREAL), Barcelona (Spain); IMIM (Hospital del Mar Research Institute), Barcelona (Spain); Kogevinas, Manolis [Centre for Research in Environmental Epidemiology (CREAL), Barcelona (Spain); IMIM (Hospital del Mar Research Institute), Barcelona (Spain); CIBER Epidemiologia y Salud Publica (CIBERESP), Barcelona (Spain); National School of Public Health, Athens (Greece); Barcelo, Damia [Department of Environmental Chemistry, IDAEA-CSIC, Barcelona (Spain); Catalan Institute for Water Research (ICRA), Girona (Spain); King Saud University, Riyadh (Saudi Arabia)

    2012-09-01

    A fast on-line analytical method based on turbulent flow chromatography (TFC) in combination with tandem mass spectrometry has been applied for the first time for the analysis of eighteen perfluoroalkyl substances (PFASs), in cord blood. A simple and rapid sample pre-treatment was optimised consisting on protein precipitation of 100 {mu}L of sample with acetonitrile (1:1) followed by centrifugation during 10 min. The method was adapted to be sensitive enough and robust with minimum sample injection volume requirements (20 {mu}L). The optimised methodology presented method limits of detection (MLOD) between 0.031 and 0.76 {mu}g/L, detection capabilities (CC{alpha}) in the range between 0.005 and 0.99 {mu}g/L and decision limits (CC{beta}) ranging from 0.006 to 1.16 {mu}g/L. The recoveries in blank blood were calculated by spiking experiments with a mixture of 18 PFASs and established between 70 and 126% for most of compounds. Isotopic dilution was carried out for quantification of selected analytes. In-house validation of this new approach was carried out according to the requirements in the 2002/657/EC Decision. Finally the good applicability of this new approach was proved by the analysis of 60 cord blood samples from two different Mediterranean cities, Barcelona (Spain) and Heraklion (Greece). Ions perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) were found at highest concentration and the more frequently compounds were PFHxS, PFOS and perfluorooctanoic acid (PFOA). The newly developed method proved to be suitable for large-scale epidemiologic studies, and to the data on PFASs exposure during pregnancy. -- Highlights: Black-Right-Pointing-Pointer An on-line method has been developed for the analysis of 18 perfluoroalkyl substances. Black-Right-Pointing-Pointer The method is based on turbulent flow chromatography tandem mass spectrometry. Black-Right-Pointing-Pointer The method was applied in 60 cord blood samples from 2 Mediterranean cities

  6. Prenatal Exposure to Perfluoroalkyl Substances and Adiposity in Early and Mid-Childhood

    Science.gov (United States)

    Mora, Ana María; Oken, Emily; Rifas-Shiman, Sheryl L.; Webster, Thomas F.; Gillman, Matthew W.; Calafat, Antonia M.; Ye, Xiaoyun; Sagiv, Sharon K.

    2016-01-01

    Background: Few studies have examined whether prenatal exposure to perfluoroalkyl substances (PFASs) is associated with childhood adiposity. Objective: We examined associations of prenatal exposure to PFASs with adiposity in early and mid-childhood. Methods: We measured plasma PFAS concentrations in 1,645 pregnant women (median, 9.6 weeks gestation) enrolled in Project Viva, a prospective pre-birth cohort study in Massachusetts (USA), between 1999 and 2002. We assessed overall and central adiposity in 1,006 children in early childhood (median, 3.2 years) and 876 in mid-childhood (median, 7.7 years) using anthropometric and dual X-ray absorptiometry (DXA) measurements. We fitted multivariable linear regression models to estimate exposure-outcome associations and evaluated effect modification by child sex. Results: Median (25–75th percentiles) prenatal plasma perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) concentrations in children assessed in early childhood were 5.6 (4.1–7.7), 24.8 (18.4–33.9), 2.4 (1.6–3.8), and 0.6 (0.5–0.9) ng/mL, respectively. Among girls, each interquartile range increment of prenatal PFOA concentrations was associated with 0.21 kg/m2 (95% CI: –0.05, 0.48) higher body mass index, 0.76 mm (95% CI: –0.17, 1.70) higher sum of subscapular and triceps skinfold thickness, and 0.17 kg/m2 (95% CI: –0.02, 0.36) higher DXA total fat mass index in mid-childhood. Similar associations were observed for PFOS, PFHxS, and PFNA. We observed null associations for boys and early-childhood adiposity measures. Conclusions: In this cohort, prenatal exposure to PFASs was associated with small increases in adiposity measurements in mid-childhood, but only among girls. Citation: Mora AM, Oken E, Rifas-Shiman SL, Webster TF, Gillman MW, Calafat AM, Ye X, Sagiv SK. 2017. Prenatal exposure to perfluoroalkyl substances and adiposity in early and mid-childhood. Environ Health

  7. Monitoring of perfluoroalkyl substances in the Ebro and Guadalquivir River basins (Spain)

    Science.gov (United States)

    Lorenzo, Maria; Campo, Julian; Andreu, Vicente; Pico, Yolanda; Farre, Marinella; Barcelo, Damia

    2015-04-01

    Relevant concentrations of a broad range of pollutants have been found in Spanish Mediterranean River basins, as consequence of anthropogenic pressures and overexploitation (Campo et al., 2014). In this study, the occurrence and sources of 21 perfluoroalkyl substances (PFASs) were determined in water and sediment of the Ebro and Guadalquivir River basins (Spain). PFASs are persistent, bio-accumulative and toxic, which make them a hazard to human health and wildlife. The Ebro and Guadalquivir Rivers are the two most important rivers of Spain. They are representative examples of Mediterranean rivers heavily managed, and previous researches have reported their high pesticide contamination (Masiá et al., 2013). Analytes were extracted by solid phase extraction (SPE) and determined by liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). In water samples, from 21 analytes screened, 11 were found in Ebro samples and 9 in Guadalquivir ones. In both basins, the most frequents were PFBA, PFPeA, PFHxS and PFOS. Maximum concentration was detected for PFBA, with 251.3 ng L-1 in Ebro and 742.9 ng L-1 in Guadalquivir. Regarding the sediment samples, 8 PFASs were detected in those coming from Ebro basin and 9 in those from Guadalquivir. The PFASs most frequently detected were PFBA, PFPeA, PFOS and PFBS. Maximum concentration in Ebro samples was detected for PFOA, with 32.4 ng g-1 dw, and in Guadalquivir samples for PFBA with 63.8 ng g-1 dw. Ubiquity of these compounds in the environment was proved with high PFAS concentration values detected in upper parts of the rivers. Results confirm that most of the PFASs are only partially eliminated during the secondary treatment suggesting that they can be a focal point of contamination to the rivers where they can bio-accumulate and produce adverse effects on wildlife and humans. Acknowledgment The Spanish Ministry of Economy and Competitiveness has supported this work through the projects SCARCE-CSD2009-00065, CGL2011

  8. Mechanistic link between uptake of sulfonamides and bacteriostatic effect: model development and application to experimental data from two soil microorganisms.

    Science.gov (United States)

    Focks, Andreas; Klasmeier, Jörg; Matthies, Michael

    2010-07-01

    Sulfonamides (SA) are antibiotic compounds that are widely used as human and veterinary pharmaceuticals. They are not rapidly biodegradable and have been detected in various environmental compartments. Effects of sulfonamides on microbial endpoints in soil have been reported from laboratory incubation studies. Sulfonamides inhibit the growth of sensitive microorganisms by competitive binding to the dihydropteroate-synthase (DHPS) enzyme of folic acid production. A mathematical model was developed that relates the extracellular SA concentration to the inhibition of the relative bacterial growth rate. Two factors--the anionic accumulation factor (AAF) and the cellular affinity factor (CAF)--determine the effective concentration of an SA. The AAF describes the SA uptake into bacterial cells and varies with both the extra- and intracellular pH values and with the acidic pKa value of an SA. The CAF subsumes relevant cellular and enzyme properties, and is directly proportional to the DHPS affinity constant for an SA. Based on the model, a mechanistic dose-response relationship is developed and evaluated against previously published data, where differences in the responses of Pseudomonas aeruginosa and Panthoea agglomerans toward changing medium pH values were found, most likely as a result of their diverse pH regulation. The derived dose-response relationship explains the pH and pKa dependency of mean effective concentration values (EC50) of eight SA and two soil bacteria based on AAF and CAF values. The mathematical model can be used to extrapolate sulfonamide effects to other pH values and to calculate the CAF as a pH-independent measure for the SA effects on microbial growth. Copyright (c) 2010 SETAC.

  9. Reduction in lipophilicity improved the solubility, plasma–protein binding, and permeability of tertiary sulfonamide RORc inverse agonists

    Energy Technology Data Exchange (ETDEWEB)

    Fauber, Benjamin P.; René, Olivier; de Leon Boenig, Gladys; Burton, Brenda; Deng, Yuzhong; Eidenschenk, Céline; Everett, Christine; Gobbi, Alberto; Hymowitz, Sarah G.; Johnson, Adam R.; La, Hank; Liimatta, Marya; Lockey, Peter; Norman, Maxine; Ouyang, Wenjun; Wang, Weiru; Wong, Harvey (Genentech); (Argenta)

    2014-08-01

    Using structure-based drug design principles, we identified opportunities to reduce the lipophilicity of our tertiary sulfonamide RORc inverse agonists. The new analogs possessed improved RORc cellular potencies with >77-fold selectivity for RORc over other nuclear receptors in our cell assay suite. The reduction in lipophilicity also led to an increased plasma–protein unbound fraction and improvements in cellular permeability and aqueous solubility.

  10. Sulfonamide-Resistant Bacteria and Their Resistance Genes in Soils Fertilized with Manures from Jiangsu Province, Southeastern China

    OpenAIRE

    Wang, Na; Yang, Xiaohong; Jiao, Shaojun; Zhang, Jun; Ye, Boping; Gao, Shixiang

    2014-01-01

    Antibiotic-resistant bacteria and genes are recognized as new environmental pollutants that warrant special concern. There were few reports on veterinary antibiotic-resistant bacteria and genes in China. This work systematically analyzed the prevalence and distribution of sulfonamide resistance genes in soils from the environments around poultry and livestock farms in Jiangsu Province, Southeastern China. The results showed that the animal manure application made the spread and abundance of a...

  11. Prevalence of Sulfonamide Resistance Genes in Bacterial Isolates from Manured Agricultural Soils and Pig Slurry in the United Kingdom▿

    OpenAIRE

    Byrne-Bailey, K. G.; Gaze, W. H.; Kay, P.; Boxall, A. B. A.; Hawkey, P. M.; Wellington, E. M. H.

    2008-01-01

    The prevalences of three sulfonamide resistance genes, sul1, sul2, and sul3 and sulfachloropyridazine (SCP) resistance were determined in bacteria isolated from manured agricultural clay soils and slurry samples in the United Kingdom over a 2-year period. Slurry from tylosin-fed pigs amended with SCP and oxytetracycline was used for manuring. Isolates positive for sul genes were further screened for the presence of class 1 and 2 integrons. Phenotypic resistance to SCP was significantly higher...

  12. Rh(III)-catalyzed oxidative olefination of N-(1-naphthyl)sulfonamides using activated and unactivated alkenes.

    Science.gov (United States)

    Li, Xuting; Gong, Xue; Zhao, Miao; Song, Guoyong; Deng, Jian; Li, Xingwei

    2011-11-04

    Rhodium(III)-catalyzed oxidative olefination of N-(1-naphthyl)sulfonamides has been achieved at the peri position. Three categories of olefins have been successfully applied. Activated olefins reacted to afford five-membered azacycles as a result of oxidative olefination-hydroamination. Unactivated olefins reacted to give the olefination product. 2-fold oxidative C-C and C-N coupling was achieved for allylbenzenes. © 2011 American Chemical Society

  13. Generic Penetration of the SSRI Market.

    Science.gov (United States)

    Cascade, Elisa F; Kalali, Amir H

    2008-04-01

    In this article, we investigate the penetration of generic selective serotonin reuptake inhibitors (SSRIs) in the US market and the implications for patient out-of-pocket expense. The data suggest that generic penetration into the SSRI market has grown from approximately nine percent in 2000, the year that the patent for Prozac((R)) expired, to 72 percent in 2007. For December, 2007, the difference in patient out-of-pocket expense for branded vs. generic agents was, on average, $55.42 for patients paying by cash (i.e., they had no prescription drug insurance) and $22.39 for patients with insurance coverage.

  14. Determination of sulfonamides in butter samples by ionic liquid magnetic bar liquid-phase microextraction high-performance liquid chromatography.

    Science.gov (United States)

    Wu, Lijie; Song, Ying; Hu, Mingzhu; Xu, Xu; Zhang, Hanqi; Yu, Aimin; Ma, Qiang; Wang, Ziming

    2015-01-01

    A novel, simple, and environmentally friendly pretreatment method, ionic liquid magnetic bar liquid-phase microextraction, was developed for the determination of sulfonamides in butter samples by high-performance liquid chromatography. The ionic liquid magnetic bar was prepared by inserting a stainless steel wire into the hollow of a hollow fiber and immobilizing ionic liquid in the micropores of the hollow fiber. In the extraction process, the ionic liquid magnetic bars were used to stir the mixture of sample and extraction solvent and enrich the sulfonamides in the mixture. After extraction, the analyte-adsorbed ionic liquid magnetic bars were readily isolated with a magnet from the extraction system. It is notable that the present method was environmentally friendly since water and only several microliters of ionic liquid were used in the whole extraction process. Several parameters affecting the extraction efficiency were investigated and optimized, including the type of ionic liquid, sample-to-extraction solvent ratio, the number of ionic liquid magnetic bars, extraction temperature, extraction time, salt concentration, stirring speed, pH of the extraction solvent, and desorption conditions. The recoveries were in the range of 73.25-103.85 % and the relative standard deviations were lower than 6.84 %. The experiment results indicated that the present method was effective for the extraction of sulfonamides in high-fat content samples.

  15. Conformer-Specific IR Spectroscopy of Laser-Desorbed Sulfonamide Drugs: Tautomeric and Conformational Preferences of Sulfanilamide and its Derivatives

    Science.gov (United States)

    Uhlemann, Thomas; Seidel, Sebastian; Müller, Christian W.

    2017-06-01

    Molecules containing the sulfonamide group R^{1}-SO_2-NHR^{2} have a longstanding history as antimicrobial agents. Even though nowadays they are not commonly used in treating humans anymore, they continue to be studied as effective inhibitors of metalloenzyme carbonic anhydrases. These enzymes are important targets for a variety of diseases, such as, for instance, breast cancer, glaucoma, and obesity. Here we present the results of our laser desorption single-conformation UV and IR study of sulfanilamide (NH_2Ph-SO_2-NHR, R=H), a variety of singly substituted derivatives, and their monohydrated complexes. Depending on the substituent, the sulfonamide group can either adopt an amino or an imino tautomeric form. The form prevalent in the crystal is not necessarily also the tautomeric form we identified in the molecular beam after laser desorbing the sample. Furthermore, we explored the effect of complexation with a single water molecule on the tautomeric and conformational preferences of the sulfonamides. Our conformer-specific IR spectra in the NH and OH stretch region (3200-3750 \\wn) suggest that the intra- and intermolecular interactions governing the structures of the monomers and water complexes are surprisingly diverse. We have undertaken both Quantum Theory of Atoms in Molecules (QTAIM) and Interacting Quantum Atoms (IQA) analyses of calculated electron densities to quantitatively characterize the nature and strengths of the intra- and intermolecular interactions prevalent in the monomer and water complex structures.

  16. Prevalence of sulfonamide resistance genes in bacterial isolates from manured agricultural soils and pig slurry in the United Kingdom.

    Science.gov (United States)

    Byrne-Bailey, K G; Gaze, W H; Kay, P; Boxall, A B A; Hawkey, P M; Wellington, E M H

    2009-02-01

    The prevalences of three sulfonamide resistance genes, sul1, sul2, and sul3 and sulfachloropyridazine (SCP) resistance were determined in bacteria isolated from manured agricultural clay soils and slurry samples in the United Kingdom over a 2-year period. Slurry from tylosin-fed pigs amended with SCP and oxytetracycline was used for manuring. Isolates positive for sul genes were further screened for the presence of class 1 and 2 integrons. Phenotypic resistance to SCP was significantly higher in isolates from pig slurry and postapplication soil than in those from preapplication soil. Of 531 isolates, 23% carried sul1, 18% sul2, and 9% sul3 only. Two percent of isolates contained all three sul genes. Class 1 and class 2 integrons were identified in 5% and 11.7%, respectively, of sul-positive isolates. In previous reports, sul1 was linked to class 1 integrons, but in this study only 8% of sul1-positive isolates carried the intI1 gene. Sulfonamide-resistant pathogens, including Shigella flexneri, Aerococcus spp., and Acinetobacter baumannii, were identified in slurry-amended soil and soil leachate, suggesting a potential environmental reservoir. Sulfonamide resistance in Psychrobacter, Enterococcus, and Bacillus spp. is reported for the first time, and this study also provides the first description of the genotypes sul1, sul2, and sul3 outside the Enterobacteriaceae and in the soil environment.

  17. Prevalence of Sulfonamide Resistance Genes in Bacterial Isolates from Manured Agricultural Soils and Pig Slurry in the United Kingdom▿

    Science.gov (United States)

    Byrne-Bailey, K. G.; Gaze, W. H.; Kay, P.; Boxall, A. B. A.; Hawkey, P. M.; Wellington, E. M. H.

    2009-01-01

    The prevalences of three sulfonamide resistance genes, sul1, sul2, and sul3 and sulfachloropyridazine (SCP) resistance were determined in bacteria isolated from manured agricultural clay soils and slurry samples in the United Kingdom over a 2-year period. Slurry from tylosin-fed pigs amended with SCP and oxytetracycline was used for manuring. Isolates positive for sul genes were further screened for the presence of class 1 and 2 integrons. Phenotypic resistance to SCP was significantly higher in isolates from pig slurry and postapplication soil than in those from preapplication soil. Of 531 isolates, 23% carried sul1, 18% sul2, and 9% sul3 only. Two percent of isolates contained all three sul genes. Class 1 and class 2 integrons were identified in 5% and 11.7%, respectively, of sul-positive isolates. In previous reports, sul1 was linked to class 1 integrons, but in this study only 8% of sul1-positive isolates carried the intI1 gene. Sulfonamide-resistant pathogens, including Shigella flexneri, Aerococcus spp., and Acinetobacter baumannii, were identified in slurry-amended soil and soil leachate, suggesting a potential environmental reservoir. Sulfonamide resistance in Psychrobacter, Enterococcus, and Bacillus spp. is reported for the first time, and this study also provides the first description of the genotypes sul1, sul2, and sul3 outside the Enterobacteriaceae and in the soil environment. PMID:19064898

  18. Insights into functional-group-tolerant polymerization catalysis with phosphine-sulfonamide palladium(II) complexes.

    Science.gov (United States)

    Jian, Zhongbao; Falivene, Laura; Wucher, Philipp; Roesle, Philipp; Caporaso, Lucia; Cavallo, Luigi; Göttker-Schnetmann, Inigo; Mecking, Stefan

    2015-01-26

    Two series of cationic palladium(II) methyl complexes {[(2-MeOC6 H4 )2 PC6 H4 SO2 NHC6 H3 (2,6-R(1) ,R(2) )]PdMe}2 [A]2 ((X) 1(+) -A: R(1) =R(2) =H: (H) 1(+) -A; R(1) =R(2) =CH(CH3 )2 : (DIPP) 1(+) -A; R(1) =H, R(2) =CF3 : (CF3) 1(+) -A; A=BF4 or SbF6 ) and neutral palladium(II) methyl complexes {[(2-MeOC6 H4 )2 PC6 H4 SO2 NC6 H3 (2,6-R(1) ,R(2) )]PdMe(L)} ((X) 1-acetone: L=acetone; (X) 1-dmso: L=dimethyl sulfoxide; (X) 1-pyr: L=pyridine) chelated by a phosphine-sulfonamide were synthesized and fully characterized. Stoichiometric insertion of methyl acrylate (MA) into all complexes revealed that a 2,1 regiochemistry dominates in the first insertion of MA. Subsequently, for the cationic complexes (X) 1(+) -A, β-H elimination from the 2,1-insertion product (X) 2(+) -AMA-2,1 is overwhelmingly favored over a second MA insertion to yield two major products (X) 4(+) -AMA-1,2 and (X) 5(+) -AMA . By contrast, for the weakly coordinated neutral complexes (X) 1-acetone and (X) 1-dmso, a second MA insertion of the 2,1-insertion product (X) 2MA-2,1 is faster than β-H elimination and gives (X) 3MA as major products. For the strongly coordinated neutral complexes (X) 1-pyr, no second MA insertion and no β-H elimination (except for (DIPP) 2-pyrMA-2,1 ) were observed for the 2,1-insertion product (X) 2-pyrMA-2,1 . The cationic complexes (X) 1(+) -A exhibited high catalytic activities for ethylene dimerization, affording butenes (C4 ) with a high selectivity of up to 97.7 % (1-butene: 99.3 %). Differences in activities and selectivities suggest that the phosphine-sulfonamide ligands remain coordinated to the metal center in a bidentate fashion in the catalytically active species. By comparison, the neutral complexes (X) 1-acetone, (X) 1-dmso, and (X) 1-pyr showed very low activity towards ethylene to give traces of oligomers. DFT analyses taking into account the two possible coordination modes (O or N) of the sulfonamide ligand for the cationic system (CF3) 1(+) suggested

  19. Molecularly Imprinted Polymer Technology: A Powerful, Generic ...

    African Journals Online (AJOL)

    Molecularly Imprinted Polymer Technology: A Powerful, Generic, Facile and Cost Effective Alternative for Enantio-recognition and Separation: A Glance at Advances and Applications. ... Tanzania Journal of Science. Journal Home · ABOUT ...

  20. Impacts of Generic Competition and Benefit Management...

    Data.gov (United States)

    U.S. Department of Health & Human Services — According to findings reported in Impacts of Generic Competition and Benefit Management Practices on Spending for Prescription Drugs - Evidence from Medicares Part D...

  1. Brand and generic medications: Are they interchangeable

    International Nuclear Information System (INIS)

    Al-Jazairi, Abdulrazak S.; Blhareth, S.; Eqtefan, Iyad S.; Al-Suwayeh, Saleh A.

    2008-01-01

    Generic substitution has become a common practice since the late 1970s in the United States. At that time, many of these generics caused bioavailability problems, which fueled suspicions about their efficacy and safety and the Food and Drug Administration (FDA) standards for bioequivalence. In Saudi Arabia, the increasing number of local products raised several concerns with regard to switching from brands to generics. Our objective was to review and examine the basis of the controversy surrounding brand and generic interchangeability and to explore a practical approach in pursuing a switch. Articles indexed initially under terms such as generic medications, generic substitution, bioequivalence and bioinequivalence were identified. These terms were used to search the indexing service, MEDLINE (1966-2006). References from the extracted articles and additional data sources, including the Code of Federal Regulations and Regulatory Guidelines from the FDA Center for Drug Evaluation and research were also reviewed. Foe most drugs, bioequivalence testing generally should enable clinicians to routinely substitute generic for innovator products. However, for narrow therapeutic, critical dose drugs, or for highly variable drugs, safe switching between products can not be assured. These drugs need special precautions and blood level monitoring upon switching. FDA firmly believes that approved generic and brand drugs can be dispensed with the full expectation that the consumer will receive the same clinical benefit. Performing the switch process is an advisable practice to reduce health care costs in countries with strong post-marketing surveillance program, but caution is to be exercised when narrow therapeutic index drugs or highly variable drugs are prescribed. (author)

  2. Generic medicine and prescribing: A quick assessment

    Directory of Open Access Journals (Sweden)

    Mainul Haque

    2017-01-01

    Full Text Available Generic drugs are copies of brand-name drugs that have exactly the same dosage, intended use, effects, side effects, route of administration, risks, safety, and strength as the original drug. In other words, their pharmacological effects are exactly the same as those of their brand-name counterparts. The Food and Drug Administration (FDA describes that generic drugs are essential possibilities that allow better access to healthcare for all Americans. They are replicas of brand-name drugs and are the identical as those of brand-name drugs in dosage form, safety, strength, route of administration, quality, performance features, and anticipated to use. Healthcare authorities and users can be guaranteed that FDA-approved generic drug products have met the same stiff principles as the innovator drug. The company that made Bayer aspirin fought in court enthusiastically to keep generic versions off the shelves, in the 1920s. The company lost in court, and consumers suddenly had an array of choices in generic aspirin. The Supreme Court of India uttering ‘the Supreme Court's ruling will prevent companies from further seeking unwarranted patents on HIV and other essential medicines.’ Generic medicine cannot be sold at a price higher than the branded medicine, so it is regularly a low-priced option. Thereafter, both the end user and the government who pay for part of the price of the medicine under the Pharmaceutical Benefits Scheme in Australia are benefitted. The treatment of diseases using essential drugs, prescribed by their generic names, has been emphasised by the WHO and many national health policies. Although there are some improvements in generic medicine prescribing, it has been advised by the WHO that ‘countries should intensify efforts to measure and regularly monitor medicine prices and availability, and adopt policy measures to address the issues identified.’

  3. Perfluoroalkyl substances exposure and thyroid hormones in humans: epidemiological observations and implications

    Directory of Open Access Journals (Sweden)

    Jung Eun Lee

    2017-03-01

    Full Text Available Thyroid hormones play crucial roles in normal neurodevelopment of fetus and child. Many chemicals can affect control and homeostasis of thyroid hormones, and eventually lead to various adverse health effects including neurodevelopmental disorders. Perfluoroalkyl substances (PFASs are among the thyroid disrupting chemicals that can be encountered among general human population. Due to their unique physicochemical characteristics, PFASs have been used as surfactants and surface coating materials in many applications. Therefore, PFASs have been frequently detected in humans and environment worldwide. In cross-sectional studies using nationally representative general human populations of United States, several PFASs have shown significant associations with thyroid hormones. Moreover, among pregnant women and their infants, not only major PFASs such as perfluorooctane sulfonic acid and perfluorooctanoic acid, but also those with shorter or longer carbon chains showed significant associations with thyroid hormones. Often demographic characteristics such as sex, age, and disease status appear to influence the associations between PFASs exposure and thyroid hormones. In general, major PFASs showed hypothyroidism effects among pregnant women and infants. As 8 carbon based PFASs have been phased out, those with shorter or longer carbon chains have been used in growing amount as replacement. However, only limited information is available for their occurrences and toxicity among humans. Further investigations on these substituting PFASs are required. In addition, efforts are warranted to identify sources of and mitigate exposure to these thyroid disrupting chemicals especially during pregnancy and early stages of life.

  4. Perfluoroalkyl and polyfluoroalkyl substances in sediments from South Bohai coastal watersheds, China

    International Nuclear Information System (INIS)

    Zhu, Zhaoyun; Wang, Tieyu; Wang, Pei; Lu, Yonglong; Giesy, John P.

    2014-01-01

    Highlights: • Relatively high concentrations of PFAS, especially PFOA, were found in the Xiaoqing River sediment. • PFOA and PFBS were the dominant PFAS in the sediments from coastal and riverine area, respectively. • Concentrations of PFNA, PFDA and PFHxS in sediment were significantly correlated with concentrations of organic carbon. • Risks posed by PFOA and PFOS to benthic organisms from concentrations of PFAS in sediments were small. - Abstract: This study investigated the concentrations and distribution of Perfluoroalkyl and polyfluoroalkyl substances (PFAS) in sediments of 12 rivers from South Bohai coastal watersheds. The highest concentrations of ΣPFAS (31.920 ng g −1 dw) and PFOA (29.021 ng g −1 dw) were found in sediments from the Xiaoqing River, which was indicative of local point sources in this region. As for other rivers, concentrations of ΣPFAS ranged from 0.218 to 1.583 ng g −1 dw were found in the coastal sediments and from 0.167 to 1.953 ng g −1 dw in the riverine sediments. Predominant PFAS from coastal and riverine areas were PFOA and PFBS, with percentages of 30% and 35%, respectively. Partitioning analysis showed the concentrations of PFNA, PFDA and PFHxS were significantly correlated with organic carbon. The results of a preliminary environmental hazard assessment showed that PFOS posed the highest hazard in the Mi River, while PFOA posed a relative higher hazard in the Xiaoqing River

  5. The occurrence, exposure and risk assessment of perfluoroalkyl acids in food from mainland, China.

    Science.gov (United States)

    Wang, Xinxuan; Zhang, Ruobing; Zhang, Hong; Wang, Yanping

    2017-11-01

    To study the contamination of perfluoroalkyl acids (PFAAs) in Chinese food and the risk of dietary exposure for the Chinese population, the data of 17 PFAAs covering 38 cities throughout China in 15 groups of foods were collected for meta-analysis from published and available research literature. Using food consumption and body weight parameters, estimated dietary intakes (EDIs) were calculated for evaluation using the Scenario-Based Risk Assessment (SceBRA) modelling. Among food groups, the highest ΣPFAAs concentrations and EDI contributions were both found in poultry (363 ng/g), fish and shrimp (313 ng/g), dark vegetables (309 ng/g), fruits (116 ng/g) and pork (25 ng/g). The EDI of adults in the high-exposure scenario was about twice that of the intermediate-exposure scenario, while the EDI of children was about twice that of adults' EDI in the intermediate-exposure scenario. In addition, the PFOS EDI for children under high exposure approached its tolerable daily intake (TDI). Therefore high dietary exposure to PFAAs is giving rise to an increased health risk, especially for children.

  6. Behaviour and fate of perfluoroalkyl and polyfluoroalkyl substances (PFASs) in drinking water treatment: a review.

    Science.gov (United States)

    Rahman, Mohammad Feisal; Peldszus, Sigrid; Anderson, William B

    2014-03-01

    This article reviews perfluoroalkyl and polyfluoroalkyl substance (PFAS) characteristics, their occurrence in surface water, and their fate in drinking water treatment processes. PFASs have been detected globally in the aquatic environment including drinking water at trace concentrations and due, in part, to their persistence in human tissue some are being investigated for regulation. They are aliphatic compounds containing saturated carbon-fluorine bonds and are resistant to chemical, physical, and biological degradation. Functional groups, carbon chain length, and hydrophilicity/hydrophobicity are some of the important structural properties of PFASs that affect their fate during drinking water treatment. Full-scale drinking water treatment plant occurrence data indicate that PFASs, if present in raw water, are not substantially removed by most drinking water treatment processes including coagulation, flocculation, sedimentation, filtration, biofiltration, oxidation (chlorination, ozonation, AOPs), UV irradiation, and low pressure membranes. Early observations suggest that activated carbon adsorption, ion exchange, and high pressure membrane filtration may be effective in controlling these contaminants. However, branched isomers and the increasingly used shorter chain PFAS replacement products may be problematic as it pertains to the accurate assessment of PFAS behaviour through drinking water treatment processes since only limited information is available for these PFASs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Key scientific issues in developing drinking water guidelines for perfluoroalkyl acids: Contaminants of emerging concern.

    Science.gov (United States)

    Post, Gloria B; Gleason, Jessie A; Cooper, Keith R

    2017-12-01

    Perfluoroalkyl acids (PFAAs), a group of synthetic organic chemicals with industrial and commercial uses, are of current concern because of increasing awareness of their presence in drinking water and their potential to cause adverse health effects. PFAAs are distinctive among persistent, bioaccumulative, and toxic (PBT) contaminants because they are water soluble and do not break down in the environment. This commentary discusses scientific and risk assessment issues that impact the development of drinking water guidelines for PFAAs, including choice of toxicological endpoints, uncertainty factors, and exposure assumptions used as their basis. In experimental animals, PFAAs cause toxicity to the liver, the immune, endocrine, and male reproductive systems, and the developing fetus and neonate. Low-dose effects include persistent delays in mammary gland development (perfluorooctanoic acid; PFOA) and suppression of immune response (perfluorooctane sulfonate; PFOS). In humans, even general population level exposures to some PFAAs are associated with health effects such as increased serum lipids and liver enzymes, decreased vaccine response, and decreased birth weight. Ongoing exposures to even relatively low drinking water concentrations of long-chain PFAAs substantially increase human body burdens, which remain elevated for many years after exposure ends. Notably, infants are a sensitive subpopulation for PFAA's developmental effects and receive higher exposures than adults from the same drinking water source. This information, as well as emerging data from future studies, should be considered in the development of health-protective and scientifically sound guidelines for PFAAs in drinking water.

  8. Perfluoroalkyl acid contamination and polyunsaturated fatty acid composition of French freshwater and marine fishes.

    Science.gov (United States)

    Yamada, Ami; Bemrah, Nawel; Veyrand, Bruno; Pollono, Charles; Merlo, Mathilde; Desvignes, Virginie; Sirot, Véronique; Oseredczuk, Marine; Marchand, Philippe; Cariou, Ronan; Antignac, Jean-Phillippe; Le Bizec, Bruno; Leblanc, Jean-Charles

    2014-07-30

    In this study, French marine and freshwater fish perfluoroalkyl acid (PFAA) contamination are presented along with their fatty acid (FA) composition to provide further elements for a risk/benefit balance of fish consumption to be assessed. The 29 most consumed marine fish species were collected in four metropolitan French coastal areas in 2004 to constitute composite samples. Geographical differences in terms of consumed species and contamination level were taken into account. Three hundred and eighty-seven composite samples corresponding to 16 freshwater fish species collected between 2008 and 2010 in the six major French rivers or their tributaries were selected among the French national agency for water and aquatic environments freshwater fish sample library. The raw edible parts were analyzed for FA composition and PFAA contamination. Results show that freshwater fishes are more contaminated by PFAAs than marine fishes and do not share the same contamination profile. Freshwater fish contamination is mostly driven by perfluorooctane sulfonate (PFOS) (75%), whereas marine fish contamination is split between perfluorooctanoic acid (PFOA) (24%), PFOS (20%), perfluorohexanoic acid (PFHxA) (15%), perfluoropentanoic acid (PFHpA) (11%), and perfluorobutanoic acid (PFBA) (11%). Common carp, pike-perch, European perch, thicklip grey mullet, and common roach presented the most unfavorable balance profile due to their high level of PFAAs and low level of n-3 long-chain polyunsaturated fatty acids (LC-PUFAs). These data could be used, if needed, in an updated opinion on fish consumption that takes into account PFAA contamination.

  9. Determination of perfluoroalkylated substances (PFASs) in drinking water from the Netherlands and Greece.

    Science.gov (United States)

    Zafeiraki, Effrosyni; Costopoulou, Danae; Vassiliadou, Irene; Leondiadis, Leondios; Dassenakis, Emmanouil; Traag, Wim; Hoogenboom, Ron L A P; van Leeuwen, Stefan P J

    2015-01-01

    In the present study 11 perfluoroalkylated substances (PFASs) were analysed in drinking tap water samples from the Netherlands (n = 37) and from Greece (n = 43) by applying LC-MS/MS and isotope dilution. PFASs concentrations above the limit of quantification, LOQ (0.6 ng/l) were detected in 20.9% of the samples from Greece. Total PFAS concentrations ranged between Netherlands. This seems attributable to the source, which is purified surface water in this area. Short-chain PFASs and especially perfluoropentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorobutane sulfonate (PFBS), and perfluorohexane sulfonate (PFHxS) were detected most frequently, whereas long-chain PFASs (C > 8) were only rarely detected. In the drinking water samples from the eastern part of the Netherlands, where drinking water is sourced from groundwater reservoirs, no PFASs were detected. This demonstrates that exposure to PFASs through drinking water in the Netherlands is dependent on the source. Additionally, five samples of bottled water from each country were analysed in the current study, with all of them originating from ground wells. In these samples, all PFASs were below the LOQ.

  10. Degradation and crosslinking of perfluoroalkyl polyethers under X-ray irradiation in ultrahigh vacuum

    International Nuclear Information System (INIS)

    Mori, S.; Morales, W.

    1989-03-01

    Degradation of three types of commercially available perfluoroalkyl polyethers (PFPE)-Demnum S200, Fomblin Z25, and Krytox 16256-by X-ray irradiation was studied by using X-ray photoemission spectroscopy (XPS) and a mass spectrometer under ultra-high-vacuum conditions. The carbons in the polymers were characterized by chemical shifts of Cls binding energies. Gaseous products containing COF2 and low-molecular-weight fluorocarbons were formed. From Fomblin Z25, which has acetal linkages (-OCF2O-), a large quantity of COF2 gas was evolved. Liquid products became tacky after a long irradiation time, and some did not dissolve in Freon. High-pressure liquid chromatography (HPLC) showed that molecular weight distribution became broader and that higher molecular weight polymers were formed from Demnum and Krytox. We concluded from these results that degradation and cross-linking took place simultaneously. Demnum crosslinked more easily than the other fluids. The time dependence of both XPS spectra of Cls and mass spectra showed that C-O-bonded carbons in PFPE'S were removed faster than other carbons. There was no substrate effect on the degradation reaction because the first-order rate constants calculated from the change of gaseous products were similar when stainless steel (440C) and gold-coated surfaces were used. Metal fluorides were formed on stainless steel during the reaction. A mechanism for the degradation of PFPE'S is discussed on the basis of their molecular structures

  11. Perfluoroalkyl substances in aquatic environment-comparison of fish and passive sampling approaches.

    Science.gov (United States)

    Cerveny, Daniel; Grabic, Roman; Fedorova, Ganna; Grabicova, Katerina; Turek, Jan; Kodes, Vit; Golovko, Oksana; Zlabek, Vladimir; Randak, Tomas

    2016-01-01

    The concentrations of seven perfluoroalkyl substances (PFASs) were investigated in 36 European chub (Squalius cephalus) individuals from six localities in the Czech Republic. Chub muscle and liver tissue were analysed at all sampling sites. In addition, analyses of 16 target PFASs were performed in Polar Organic Chemical Integrative Samplers (POCISs) deployed in the water at the same sampling sites. We evaluated the possibility of using passive samplers as a standardized method for monitoring PFAS contamination in aquatic environments and the mutual relationships between determined concentrations. Only perfluorooctane sulphonate was above the LOQ in fish muscle samples and 52% of the analysed fish individuals exceeded the Environmental Quality Standard for water biota. Fish muscle concentration is also particularly important for risk assessment of fish consumers. The comparison of fish tissue results with published data showed the similarity of the Czech results with those found in Germany and France. However, fish liver analysis and the passive sampling approach resulted in different fish exposure scenarios. The total concentration of PFASs in fish liver tissue was strongly correlated with POCIS data, but pollutant patterns differed between these two matrices. The differences could be attributed to the metabolic activity of the living organism. In addition to providing a different view regarding the real PFAS cocktail to which the fish are exposed, POCISs fulfil the Three Rs strategy (replacement, reduction, and refinement) in animal testing. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Photocatalytic removal of perfluoroalkyl substances from water and wastewater: Mechanism, kinetics and controlling factors.

    Science.gov (United States)

    Xu, Bentuo; Ahmed, Mohammad Boshir; Zhou, John L; Altaee, Ali; Wu, Minghong; Xu, Gang

    2017-12-01

    This review focuses on heterogeneous photocatalysis of perfluoroalkyl substances (PFAS) which are of worldwide concern as emerging persistent organic contaminants. Heterogeneous photocatalysis is an effective and advanced technology for PFAS removal from water with relatively high efficacy. During photocatalysis, various short chain perfluorocarboxylic acids (PFCA) are produced as intermediates and the efficacy is related to the photo-generated hole (h + ) and photo-generated electron (e - ). PFAS photodegradation in water under UV irradiation is most effective by using In 2 O 3 as the catalyst, followed by Ga 2 O 3 and TiO 2 . Significantly, modifying the chemical composition or morphology of the catalyst can improve its efficacy for PFAS removal. In 2 O 3 porous nanoplates were found to have the best performance of 100% PFAS decomposition under UV light with rate constant (k t ) and half-time (τ 1/2 ) of 0.158 min -1 and 4.4 min, respectively. Catalysts perform well in acidic solution and increasing temperature to a certain extent. The photocatalytic performance is reduced when treating wastewater due to the presence of dissolved organic matter (DOM), with the catalysts following the order: needle-like Ga 2 O 3  > In 2 O 3  > TiO 2 . Future studies should focus on the development of novel photocatalysts, and their immobilization and application for PFAS removal in wastewater. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Research Article. Perfluoroalkylated substances in human urine: results of a biomonitoring pilot study

    Directory of Open Access Journals (Sweden)

    Hartmann Christina

    2017-04-01

    Full Text Available Perfluoroalkylated substances (PFASs are a class of synthetic chemicals used in a wide range of processes and products due to their unique physicalchemical properties. Through intake of PFASs via food or several consumer products, humans can be exposed. Long-chain PFASs have been associated with adverse effects in laboratory animals, and there is also evidence for adverse health effects in humans. Although investigations of human exposure are mainly conducted in blood samples, some studies have shown that especially short-chain PFASs can be detected in human urine. In the present study, a sensitive analytical method was adapted for the measurement of 12 PFASs in human urine samples by HPLC-MS/MS. For verifying this method, concentrations in 11 male and female participants aged 25-46 years were analysed. In the study population, ranges of urinary PFASs concentrations were n.d.- 8.5 ng/l for perfluoropentanoic acid,

  14. Variability and predictors of serum perfluoroalkyl substance concentrations during pregnancy and early childhood.

    Science.gov (United States)

    Kingsley, Samantha L; Eliot, Melissa N; Kelsey, Karl T; Calafat, Antonia M; Ehrlich, Shelley; Lanphear, Bruce P; Chen, Aimin; Braun, Joseph M

    2018-08-01

    Exposure to poly- and perfluoroalkyl substances (PFAS), ubiquitous and persistent environmental contaminants, could be associated with adverse health outcomes, but there are limited longitudinal data assessing patterns and predictors of exposure during childhood. We quantified concentrations of eight different PFAS in sera collected from women during pregnancy and children at delivery and ages 3 and 8 years in 367 mother-child pairs enrolled in a prospective cohort from 2003 to 2006. In general, median childhood PFAS concentrations increased from birth to age 3 and then decreased by age 8. Maternal serum PFAS concentrations during pregnancy were strongly correlated with cord serum concentrations (0.76 PFAS concentrations, including income, race, and parity. In children, serum PFAS concentrations were associated with maternal age at delivery, race, parity, and child age. Breastfeeding duration was positively associated with childhood PFAS concentrations at ages 3 and 8 years. In addition, stain repellant use was associated with higher perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations at age 8 years. Serum PFAS concentrations are higher during early childhood, a potentially sensitive period of development, and were highest among breastfed children. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Transport of perfluoroalkyl substances (PFAS) from an arctic glacier to downstream locations: implications for sources.

    Science.gov (United States)

    Kwok, Karen Y; Yamazaki, Eriko; Yamashita, Nobuyoshi; Taniyasu, Sachi; Murphy, Margaret B; Horii, Yuichi; Petrick, Gert; Kallerborn, Roland; Kannan, Kurunthachalam; Murano, Kentaro; Lam, Paul K S

    2013-03-01

    Perfluoroalkyl substances (PFAS) have been globally detected in various environmental matrices, yet their fate and transport to the Arctic is still unclear, especially for the European Arctic. In this study, concentrations of 17 PFAS were quantified in two ice cores (n=26), surface snow (n=9) and surface water samples (n=14) collected along a spatial gradient in Svalbard, Norway. Concentrations of selected ions (Na(+), SO4(2-), etc.) were also determined for tracing the origins and sources of PFAS. Perfluorobutanoate (PFBA), perfluorooctanoate (PFOA) and perfluorononanoate (PFNA) were the dominant compounds found in ice core samples. Taking PFOA, PFNA and perfluorooctane-sulfonate (PFOS) as examples, higher concentrations were detected in the middle layers of the ice cores representing the period of 1997-2000. Lower concentrations of C8-C12 perfluorocarboxylates (PFCAs) were detected in comparison with concentrations measured previously in an ice core from the Canadian Arctic, indicating that contamination levels in the European Arctic are lower. Average PFAS concentrations were found to be lower in surface snow and melted glacier water samples, while increased concentrations were observed in river water downstream near the coastal area. Perfluorohexanesulfonate (PFHxS) was detected in the downstream locations, but not in the glacier, suggesting existence of local sources of this compound. Long-range atmospheric transport of PFAS was the major deposition pathway for the glaciers, while local sources (e.g., skiing activities) were identified in the downstream locations. Copyright © 2012 Elsevier B.V. All rights reserved.

  16. Placental Transfer of Perfluoroalkyl Substances and Associations with Thyroid Hormones: Beijing Prenatal Exposure Study

    Science.gov (United States)

    Yang, Lin; Li, Jingguang; Lai, Jianqiang; Luan, Hemi; Cai, Zongwei; Wang, Yibaina; Zhao, Yunfeng; Wu, Yongning

    2016-02-01

    Perfluoroalkyl substances (PFASs) have been detected in wildlife and human samples worldwide. Toxicology research showed that PFASs could interfere with thyroid hormone homeostasis. In this study, eight PFASs, fifteen PFAS precursors and five thyroid hormones were analyzed in 157 paired maternal and cord serum samples collected in Beijing around delivery. Seven PFASs and two precursors were detected in both maternal and cord sera with significant maternal-fetal correlations (r = 0.336 to 0.806, all P < 0.001). The median ratios of major PFASs concentrations in fetal versus maternal serum were from 0.25:1 (perfluorodecanoic acid, PFDA) to 0.65:1 (perfluorooctanoic acid, PFOA). Spearman partial correlation test showed that maternal thyroid stimulating hormone (TSH) was negatively correlated with most maternal PFASs (r = -0.261 to -0.170, all P < 0.05). Maternal triiodothyronin (T3) and free T3 (FT3) showed negative correlations with most fetal PFASs (r = -0.229 to -0.165 for T3; r = -0.293 to -0.169 for FT3, all P < 0.05). Our results suggest prenatal exposure of fetus to PFASs and potential associations between PFASs and thyroid hormone homeostasis in humans.

  17. Perfluoroalkyl substances in human bone: concentrations in bones and effects on bone cell differentiation.

    Science.gov (United States)

    Koskela, A; Koponen, J; Lehenkari, P; Viluksela, M; Korkalainen, M; Tuukkanen, J

    2017-07-28

    Perfluoroalkyl substances (PFAS), including two most commonly studied compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), are widely distributed environmental pollutants, used extensively earlier. Due to their toxicological effects the use of PFAS is now regulated. Based on earlier studies on PFOA's distribution in bone and bone marrow in mice, we investigated PFAS levels and their possible link to bone microarchitecture of human femoral bone samples (n = 18). Soft tissue and bone biopsies were also taken from a 49-year old female cadaver for PFAS analyses. We also studied how PFOA exposure affects differentiation of human osteoblasts and osteoclasts. PFAS were detectable from all dry bone and bone marrow samples, PFOS and PFOA being the most prominent. In cadaver biopsies, lungs and liver contained the highest concentrations of PFAS, whereas PFAS were absent in bone marrow. Perfluorononanoic acid (PFNA) was present in the bones, PFOA and PFOS were absent. In vitro results showed no disturbance in osteogenic differentiation after PFOA exposure, but in osteoclasts, lower concentrations led to increased resorption, which eventually dropped to zero after increase in PFOA concentration. In conclusion, PFAS are present in bone and have the potential to affect human bone cells partly at environmentally relevant concentrations.

  18. Maternal Concentrations of Perfluoroalkyl Substances and Fetal Markers of Metabolic Function and Birth Weight

    Science.gov (United States)

    Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E.; Bouchard, Maryse F.; Fisher, Mandy; Morriset, Anne-Sophie; Monnier, Patricia; Shapiro, Gabriel D.; Ettinger, Adrienne S.; Dallaire, Renee; Taback, Shayne; Fraser, William; Platt, Robert W.

    2017-01-01

    Abstract Perfluoroalkyl substances (PFAS) are ubiquitous, persistent chemicals that have been widely used in the production of common household and consumer goods for their nonflammable, lipophobic, and hydrophobic properties. Inverse associations between maternal or umbilical cord blood concentrations of perfluorooctanoic acid and perfluorooctanesulfonate and birth weight have been identified. This literature has primarily examined each PFAS individually without consideration of the potential influence of correlated exposures. Further, the association between PFAS exposures and indicators of metabolic function (i.e., leptin and adiponectin) has received limited attention. We examined associations between first-trimester maternal plasma PFAS concentrations and birth weight and cord blood concentrations of leptin and adiponectin using data on 1,705 mother-infant pairs from the Maternal Infant Research on Environmental Chemicals (MIREC) Study, a trans-Canada birth cohort study that recruited women between 2008 and 2011. Bayesian hierarchical models were used to quantify associations and calculate credible intervals. Maternal perfluorooctanoic acid concentrations were inversely associated with birth weight z score, though the null value was included in all credible intervals (log10 β = −0.10, 95% credible interval: −0.34, 0.13). All associations between maternal PFAS concentrations and cord blood adipocytokine concentrations were of small magnitude and centered around the null value. Follow-up in a cohort of children is required to determine how the observed associations manifest in childhood. PMID:28172036

  19. Immunotoxicity in green mussels under perfluoroalkyl substance (PFAS) exposure: Reversible response and response model development.

    Science.gov (United States)

    Liu, Changhui; Gin, Karina Yew-Hoong

    2018-04-01

    The immunotoxicity of 4 commonly detected perfluoroalkyl substances (PFASs), namely, perfluorooctanesulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA) was investigated by measuring biomarkers of the immune profile of green mussels, Perna viridis. The biomarkers included neutral red retention, phagocytosis, and spontaneous cytotoxicity, all of which were tested on mussel hemocytes. Hemocytes are an important component of the invertebrate immune system. We found that exposure to PFASs could lead to reduced hemocyte cell viability and suppress immune function by up to 50% of normal performance within the experimental exposure range. The results indicate that PFASs have an immunotoxic potential and thus could pose severe health risks to aquatic organisms. The reported immunotoxicity is likely to result from the compounds' direct and indirect interactions with the hemocyte membrane, and therefore likely to affect the functionality of these cells. The immunotoxic response was found to be related to the organism's burden of PFASs, and was reversible when the compounds were removed from the test organisms. Based on this relationship, models using an organism's PFAS concentration and bioaccumulation factor (BAF) as the independent variables were established to quantify PFAS-induced immunotoxicity. The models help us to gain a better understanding of the toxic mechanism of PFASs, and provide a tool to evaluate adverse effects for the whole group of compounds with one mathematical equation. Environ Toxicol Chem 2018;37:1138-1145. © 2018 SETAC. © 2018 SETAC.

  20. Transfer of perfluoroalkyl substances from mother to fetus in a Spanish birth cohort.

    Science.gov (United States)

    Manzano-Salgado, Cyntia B; Casas, Maribel; Lopez-Espinosa, Maria-Jose; Ballester, Ferran; Basterrechea, Mikel; Grimalt, Joan O; Jiménez, Ana-María; Kraus, Thomas; Schettgen, Thomas; Sunyer, Jordi; Vrijheid, Martine

    2015-10-01

    Prenatal exposure to perfluoroalkyl substances (PFAS) might affect child health; thus estimating PFAS fetal burden is relevant. PFAS fetal burden is best estimated in cord samples; previous studies have used either maternal plasma or serum during pregnancy as proxy, but their validity is not clear. We aimed to evaluate PFAS transfer between mother and fetus and determine its predictors in a Spanish birth cohort. We measured perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA) in maternal blood and cord serum from 66 mother-child pairs. We used Spearman's rank coefficients to correlate PFAS concentrations in first trimester maternal plasma and serum, with cord serum samples. We assessed PFAS placental transfer by calculating maternal to cord ratios and examined their association with maternal socio-demographic characteristics and child sex using linear regression models. Median concentrations of PFAS (ng/mL) of PFHxS, PFOS, PFOA, and PFNA in maternal plasma (0.79, 6.18, 2.85 and 0.84, respectively) and serum (0.84, 6.99, 2.97 and 0.85) were higher than in cord serum (0.40, 1.86, 1.90 and 0.32). PFBS was not detected. Positive Spearman's correlations (p-valuesPFAS fetal body burden can be assessed using as proxy maternal plasma or serum collected early in pregnancy. Maternal age might influence PFAS placental transfer. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Prenatal concentrations of Perfluoroalkyl substances and early communication development in British girls.

    Science.gov (United States)

    Jeddy, Zuha; Hartman, Terryl J; Taylor, Ethel V; Poteete, Cayla; Kordas, Katarzyna

    2017-06-01

    Perfluoroalkyl substances (PFAS), found in many household products and classed as endocrine disrupting chemicals, can be transferred through the placenta and are associated with multiple developmental deficits in offspring. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we investigated the association between intrauterine exposure to PFAS and early communication development in 432 mother-daughter dyads at 15 and 38months of age. Concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA) were measured in maternal serum collected during pregnancy. Early communication development was measured with the ALSPAC-adapted MacArthur Communicative Development Inventories for Infants and Toddlers. The infant questionnaire measured verbal comprehension, vocabulary comprehension and production, nonverbal communication, and social development. The toddler questionnaire measured language, intelligibility, and communicative sub-scores. Multivariable linear regression was used to examine associations between each PFAS exposure and each communication sub-scale score. The association between maternal PFAS concentrations and early communication development at 15 and 38months of age varied by maternal age at delivery. In daughters of younger mothers (PFAS was positively and negatively associated with communication development among girls, with inconsistent pattern of association across all measured PFAS and endpoints. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Updated national emission of perfluoroalkyl substances (PFASs) from wastewater treatment plants in South Korea.

    Science.gov (United States)

    Kwon, Hye-Ok; Kim, Hee-Young; Park, Yu-Mi; Seok, Kwang-Seol; Oh, Jeong-Eun; Choi, Sung-Deuk

    2017-01-01

    A nationwide emission estimate of perfluoroalkyl substances (PFASs) from wastewater treatment plants (WWTPs) is required to understand the source-receptor relationship of PFASs and to manage major types of WWTPs. In this study, the concentrations of 13 PFASs (8 perfluorocarboxylic acids, 3 perfluoroalkane sulfonates, and 2 intermediates) in wastewater and sludge from 81 WWTPs in South Korea were collected. The emission pathways of PFASs were redefined, and then the national emission of PFASs from WWTPs was rigorously updated. In addition to the direct calculations, Monte Carlo simulations were also used to calculate the likely range of PFAS emissions. The total (Σ 13 PFAS) emission (wastewater + sludge) calculated from the direct calculation with mean concentrations was 4.03 ton/y. The emissions of perfluorooctanoic acid (PFOA, 1.19 ton/y) and perfluorooctane sulfonate (PFOS, 1.01 ton/y) were dominant. The Monte Carlo simulations suggested that the realistic national emission of Σ 13 PFASs is between 2 ton/y and 20 ton/y. Combined WWTPs treating municipal wastewater from residential and commercial areas were identified as a major emission source, contributing 65% to the total PFAS emissions. The Han and Nakdong Rivers were the primary contaminated rivers, receiving 89% of the total PFAS discharge from WWTPs. The results and methodologies in this study can be useful to establish a management policy for PFASs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Quantitative bias analysis for epidemiological associations of perfluoroalkyl substance serum concentrations and early onset of menopause.

    Science.gov (United States)

    Ruark, Christopher D; Song, Gina; Yoon, Miyoung; Verner, Marc-André; Andersen, Melvin E; Clewell, Harvey J; Longnecker, Matthew P

    2017-02-01

    An association between increased serum concentrations of perfluoroalkyl substances (PFAS) such as perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and early menopause has been reported (Knox et al., 2011; Taylor et al., 2014). This association may be explained by the fact that women who underwent menopause no longer excrete PFAS through menstruation. Our objective was to assess how much of the epidemiologic association between PFAS and altered timing of menopause might be explained by reverse causality. We extended a published population life-stage physiologically-based pharmacokinetic (PBPK) model of PFOS and PFOA characterized by realistic distributions of physiological parameters including age at menopause. We then conducted Monte Carlo simulations to replicate the Taylor population (Taylor et al., 2014) and the Knox population (Knox et al., 2011). The analysis of the simulated data overall showed a pattern of results that was comparable to those reported in epidemiological studies. For example, in the simulated Knox population (ages 42-51) the odds ratio (OR) for menopause in the fifth quintile of PFOA compared to those in the first quintile was 1.33 (95% CI 1.26-1.40), whereas the reported OR was 1.4 (95% CI 1.1-1.8). Using our model structure, a substantial portion of the associations reported can be explained by pharmacokinetics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Occurrence, fluxes and sources of perfluoroalkyl substances with isomer analysis in the snow of northern China.

    Science.gov (United States)

    Shan, Guoqiang; Chen, Xinwei; Zhu, Lingyan

    2015-12-15

    In this study, perfluoroalkyl substances (PFASs) and the isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) were analyzed in fresh snow samples collected from 19 cities in northern China, 2013. The levels of total PFASs in the snow samples were 33.5-229 ng/L, suggesting heavy atmospheric pollution of PFASs in northern China. PFOA (9.08-107 ng/L), PFOS (3.52-54.3 ng/L), perfluoroheptanoate (PFHpA) (3.66-44.8 ng/L), and perfluorohexanoate (PFHxA) (3.21-23.6 ng/L) were predominant with a summed contribution of 82% to the total PFASs. The particulate matters (PMs) associated PFASs contributed 21.5-56.2% to the total PFASs in the snow, suggesting PMs are vital for the transport and deposition of airborne PFASs. Partitioning of PFASs between PM and dissolved phases was dependent on the carbon chain length and end functional groups. Isomer profiles of PFOA and PFOS in the snow were in agreement with the signature of the historical 3M electrochemical fluorination (ECF) products, suggesting that the ECF products were still produced and used in China. Further source analysis showed that the airborne PFASs in urban area were mainly due to direct release rather than degradation of their precursors. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Plasma Concentrations of Perfluoroalkyl Substances and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Sun, Qi; Zong, Geng; Valvi, Damaskini

    2018-01-01

    between PFAS exposures and subsequent incidence of T2D in the Nurses' Health Study II (NHSII). In addition, we aimed to evaluate potential demographic and lifestyle determinants of plasma PFAS concentrations. METHODS: A prospective nested case-control study of T2D was conducted among participants who were......BACKGROUND: Emerging evidence suggests that perfluoroalkyl substances (PFASs) are endocrine disruptors and may contribute to the etiology of type 2 diabetes (T2D), but this hypothesis needs to be clarified in prospective human studies. OBJECTIVES: Our objective was to examine the associations...... free of diabetes, cardiovascular disease, and cancer in 1995-2000 [(mean±SD): 45.3±4.4y) of age]. We identified and ascertained 793 incident T2D cases through 2011 (mean±SD) years of follow-up: 6.7±3.7y). Each case was individually matched to a control (on age, month and fasting status at sample...

  6. Acids and alkali resistant sticky superhydrophobic surfaces by one-pot electropolymerization of perfluoroalkyl alkyl pyrrole.

    Science.gov (United States)

    Nicolas, Mael

    2010-03-15

    Over the past few years, electropolymerization of semifluorinated monomers like thiophene or pyrrole has been used as a gentle and effective method to generate, in one step, stable superhydrophobic surfaces. The synthetic route mostly involves the coupling reaction between a carboxylic acid and an alcohol, using a carboxy group-activated reagent and a catalyst. As a consequence, the electroformed surfaces present high liquid repellency due to the concomitant effect of roughness and low surface energy. Nevertheless, the ester connector can be cleaved under acidic and basic conditions, preventing its use under a range of environmental conditions. To overcome this drawback, a new perfluoroalkyl alkyl pyrrole has been synthesized, the fluorinated segment being connected to the electropolymerizable part via an alkyl chain, and electropolymerized, leading to surfaces that exhibit a static contact angle with water superior to 150 degrees and no sliding angle, over a wide pH range and with a long lifetime. This represents the first example of a pure conducting polymer surface with sticky superhydrophobicity not only in pure water but also in corrosive solutions such as acids and bases, giving rise to new prospects in practical applications. 2009 Elsevier Inc. All rights reserved.

  7. Design, Synthesis, and Evaluation of Dihydrobenzo[cd]indole-6-sulfonamide as TNF-alpha Inhibitors

    Science.gov (United States)

    Deng, Xiaobing; Zhang, Xiaoling; Tang, Bo; Liu, Hongbo; Shen, Qi; Liu, Ying; Lai, Luhua

    2018-04-01

    Tumor necrosis factor-α (TNF-α) plays a pivotal role in inflammatory response. Dysregulation of TNF can lead to a variety of disastrous pathological effects, including auto-inflammatory diseases. Antibodies that directly targeting TNF-α have been proven effective in suppressing symptoms of these disorders. Compared to protein drugs, small molecule drugs are normally orally available and less expensive. Till now, peptide and small molecule TNF-α inhibitors are still in the early stage of development, and much more efforts should be made. In a previously study, we reported a TNF-α inhibitor, EJMC-1 with modest activity. Here, we optimized this compound by shape screen and rational design. In the first round, we screened commercial compound library for EJMC-1 analogs based on shape similarity. Out of the 68 compounds tested, 20 compounds showed better binding affinity than EJMC-1 in the SPR competitive binding assay. These 20 compounds were tested in cell assay and the most potent compound was 2-oxo-N-phenyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide (S10) with an IC50 of 14 M, which was 2.2-fold stronger than EJMC-1. Based on the docking analysis of S10 and EJMC-1 binding with TNF-α, in the second round, we designed S10 analogues, purchased 7 of them and synthesized 7 new compounds. The best compound, 4e showed an IC50 value of 3 M in cell assay, which was 14-fold stronger than EJMC-1. 4e was among the most potent TNF-α organic compound inhibitors reported so far. Our study demonstrated that 2-oxo-N-phenyl-1,2-dihydrobenzo[cd]indole-6-sulfonamide analogues could be developed as potent TNF-α inhibitors. 4e can be further optimized for its activity and properties. Our study provides insights into designing small molecule inhibitors directly targeting TNF-α and for protein-protein interaction inhibitor design.

  8. Prevalence and characterization of plasmids carrying sulfonamide resistance genes among Escherichia coli from pigs, pig carcasses and human.

    Science.gov (United States)

    Wu, Shuyu; Dalsgaard, Anders; Hammerum, Anette M; Porsbo, Lone J; Jensen, Lars B

    2010-07-30

    Sulfonamide resistance is very common in Escherichia coli. The aim of this study was to characterize plasmids carrying sulfonamide resistance genes (sul1, sul2 and sul3) in E. coli isolated from pigs and humans with a specific objective to assess the genetic diversity of plasmids involved in the mobility of sul genes. A total of 501 E. coli isolates from pig feces, pig carcasses and human stools were tested for their susceptibility to selected antimicrobial. Multiplex PCR was conducted to detect the presence of three sul genes among the sulfonamide-resistant E. coli isolates. Fifty-seven sulfonamide-resistant E. coli were selected based on presence of sul resistance genes and subjected to conjugation and/or transformation experiments. S1 nuclease digestion followed by pulsed-field gel electrophoresis was used to visualize and determine the size of plasmids. Plasmids carrying sul genes were characterized by PCR-based replicon typing to allow a comparison of the types of sul genes, the reservoir and plasmid present. A total of 109/501 isolates exhibited sulfonamide resistance. The relative prevalences of sul genes from the three reservoirs (pigs, pig carcasses and humans) were 65%, 45% and 12% for sul2, sul1, and sul3, respectively. Transfer of resistance through conjugation was observed in 42/57 isolates. Resistances to streptomycin, ampicillin and trimethoprim were co-transferred in most strains. Class 1 integrons were present in 80% of sul1-carrying plasmids and 100% of sul3-carrying plasmids, but only in 5% of sul2-carrying plasmids. The sul plasmids ranged from 33 to 160-kb in size and belonged to nine different incompatibility (Inc) groups: FII, FIB, I1, FIA, B/O, FIC, N, HI1 and X1. IncFII was the dominant type in sul2-carrying plasmids (52%), while IncI1 was the most common type in sul1 and sul3-carrying plasmids (33% and 45%, respectively). Multireplicons were found associated with all three sul genes. Sul genes were distributed widely in E. coli isolated

  9. Prevalence and characterization of plasmids carrying sulfonamide resistance genes among Escherichia coli from pigs, pig carcasses and human

    Directory of Open Access Journals (Sweden)

    Hammerum Anette M

    2010-07-01

    Full Text Available Abstract Background Sulfonamide resistance is very common in Escherichia coli. The aim of this study was to characterize plasmids carrying sulfonamide resistance genes (sul1, sul2 and sul3 in E. coli isolated from pigs and humans with a specific objective to assess the genetic diversity of plasmids involved in the mobility of sul genes. Methods A total of 501 E. coli isolates from pig feces, pig carcasses and human stools were tested for their susceptibility to selected antimicrobial. Multiplex PCR was conducted to detect the presence of three sul genes among the sulfonamide-resistant E. coli isolates. Fifty-seven sulfonamide-resistant E. coli were selected based on presence of sul resistance genes and subjected to conjugation and/or transformation experiments. S1 nuclease digestion followed by pulsed-field gel electrophoresis was used to visualize and determine the size of plasmids. Plasmids carrying sul genes were characterized by PCR-based replicon typing to allow a comparison of the types of sul genes, the reservoir and plasmid present. Results A total of 109/501 isolates exhibited sulfonamide resistance. The relative prevalences of sul genes from the three reservoirs (pigs, pig carcasses and humans were 65%, 45% and 12% for sul2, sul1, and sul3, respectively. Transfer of resistance through conjugation was observed in 42/57 isolates. Resistances to streptomycin, ampicillin and trimethoprim were co-transferred in most strains. Class 1 integrons were present in 80% of sul1-carrying plasmids and 100% of sul3-carrying plasmids, but only in 5% of sul2-carrying plasmids. The sul plasmids ranged from 33 to 160-kb in size and belonged to nine different incompatibility (Inc groups: FII, FIB, I1, FIA, B/O, FIC, N, HI1 and X1. IncFII was the dominant type in sul2-carrying plasmids (52%, while IncI1 was the most common type in sul1 and sul3-carrying plasmids (33% and 45%, respectively. Multireplicons were found associated with all three sul genes

  10. Perfluoroalkylated acids in the eggs of great tits (Parus major) near a fluorochemical plant in Flanders, Belgium.

    Science.gov (United States)

    Groffen, Thimo; Lopez-Antia, Ana; D'Hollander, Wendy; Prinsen, Els; Eens, Marcel; Bervoets, Lieven

    2017-09-01

    Perfluoroalkyl acids (PFAAs) are highly persistent substances which have been detected in wildlife around the world, including birds. Although bird eggs have often been used to determine and monitor PFAAs levels in the marine environment, this has rarely been done in the terrestrial environment. In the present study we examined the concentrations and composition profile of 12 PFAAs (4 perfluoroalkyl sulfonic acids (PFSAs) and 8 perfluoroalkyl carboxylic acids (PFCAs) in the eggs of great tits (Parus major) collected at a fluorochemical plant and in three other areas, representing a gradient in distance from the pollution source (from 1 to 70 km), in Antwerp, Belgium. The PFSA concentrations measured at the site of the fluorochemical plant were among the highest ever reported in eggs with median concentrations of 10380 ng/g (extrapolated), 99.3 ng/g and 47.7 ng/g for PFOS, PFHxS and PFDS respectively. Furthermore, the median concentration of 19.8 ng/g for PFOA was also among the highest ever reported in bird eggs. Although these concentrations decreased sharply with distance from the fluorochemical plant, levels found in the adjacent sites were still high compared to what has been reported in literature. Moreover, based on what is known in literature, it is likely that these concentrations may cause toxicological effects. PFOS was the dominant contributor to the PFSA and PFAAs (63.4-97.6%) profile at each site, whereas for PFCAs this was PFOA at the plant site and the nearest locations (41.0-52.8%) but PFDoA (37.7%) at the farthest location. Although there is some evidence that PFAAs concentrations close to the plant site are decreasing in comparison with earlier measurements, which may be due to the phase out of PFOS, more research is necessary to understand the extent of the toxicological effects in the vicinity of this PFAAs hotspot. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Diet and metabolic state are the main factors determining concentrations of perfluoroalkyl substances in female polar bears from Svalbard.

    Science.gov (United States)

    Tartu, Sabrina; Bourgeon, Sophie; Aars, Jon; Andersen, Magnus; Lone, Karen; Jenssen, Bjørn Munro; Polder, Anuschka; Thiemann, Gregory W; Torget, Vidar; Welker, Jeffrey M; Routti, Heli

    2017-10-01

    Perfluoroalkyl substances (PFASs) have been detected in organisms worldwide, including Polar Regions. The polar bear (Ursus maritimus), the top predator of Arctic marine ecosystems, accumulates high concentrations of PFASs, which may be harmful to their health. The aim of this study was to investigate which factors (habitat quality, season, year, diet, metabolic state [i.e. feeding/fasting], breeding status and age) predict PFAS concentrations in female polar bears captured on Svalbard (Norway). We analysed two perfluoroalkyl sulfonates (PFSAs: PFHxS and PFOS) and C 8 -C 13 perfluoroalkyl carboxylates (PFCAs) in 112 plasma samples obtained in April and September 2012-2013. Nitrogen and carbon stable isotope ratios (δ 15 N, δ 13 C) in red blood cells and plasma, and fatty acid profiles in adipose tissue were used as proxies for diet. We determined habitat quality based on movement patterns, capture position and resource selection functions, which are models that predict the probability of use of a resource unit. Plasma urea to creatinine ratios were used as proxies for metabolic state (i.e. feeding or fasting state). Results were obtained from a conditional model averaging of 42 general linear mixed models. Diet was the most important predictor of PFAS concentrations. PFAS concentrations were positively related to trophic level and marine diet input. High PFAS concentrations in females feeding on the eastern part of Svalbard, where the habitat quality was higher than on the western coast, were likely related to diet and possibly to abiotic factors. Concentrations of PFSAs and C 8 -C 10 PFCAs were higher in fasting than in feeding polar bears and PFOS was higher in females with cubs of the year than in solitary females. Our findings suggest that female polar bears that are exposed to the highest levels of PFAS are those 1) feeding on high trophic level sea ice-associated prey, 2) fasting and 3) with small cubs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Sharing, samples, and generics: an antitrust framework.

    Science.gov (United States)

    Carrier, Michael A

    Rising drug prices are in the news. By increasing price, drug companies have placed vital, even life-saving, medicines out of the reach of consumers. In a recent development, brand firms have prevented generics even from entering the market. The ruse for this strategy involves risk-management programs known as Risk Evaluation and Mitigation Strategies ("REMS"). Pursuant to legislation enacted in 2007, the FDA requires REMS when a drug's risks (such as death or injury) outweigh its rewards. Brands have used this regime, intended to bring drugs to the market, to block generic competition. Regulations such as the federal Hatch-Waxman Act and state substitution laws foster widespread generic competition. But these regimes can only be effectuated through generic entry. And that entry can take place only if a generic can use a brand's sample to show that its product is equivalent. More than 100 generic firms have complained that they have not been able to access needed samples. One study of 40 drugs subject to restricted access programs found that generics' inability to enter cost more than $5 billion a year. Brand firms have contended that antitrust law does not compel them to deal with their competitors and have highlighted concerns related to safety and product liability in justifying their refusals. This Article rebuts these claims. It highlights the importance of samples in the regulatory regime and the FDA's inability to address the issue. It shows how a sharing requirement in this setting is consistent with Supreme Court caselaw. And it demonstrates that the brands' behavior fails the defendant-friendly "no economic sense" test because the conduct literally makes no sense other than by harming generics. Brands' denial of samples offers a textbook case of monopolization. In the universe of pharmaceutical antitrust behavior, other conduct--such as "pay for delay" settlements between brands and generics and "product hopping" from one drug to a slightly modified

  13. Refractive index modulation in the polyurethane films containing diazo sulfonamide chromophores

    Energy Technology Data Exchange (ETDEWEB)

    Ortyl, E. [Insitute of Organic and Polymer Technology, WrocIaw University of Technology, 50-384 WrocIaw (Poland); Kucharski, S. [Insitute of Organic and Polymer Technology, WrocIaw University of Technology, 50-384 WrocIaw (Poland)]. E-mail: stanislaw.kucharski@pwr.wroc.pl; Gotszalk, T. [Faculty of Microsystem Electronics and Photonics, WrocIaw University of Technology, 50-384 WrocIaw (Poland)

    2005-05-23

    The series of photochromic polyurethanes was obtained by modification of precursor polymers prepared from 4,4'-diphenylmethane diisocyanate (MDI), hexamethylene 1,6-diisocyanate (HDI) or toluene 2,4-diisocyanate (TDI) and N,N'-di-(2-hydroxyethyl) aniline. The precursor polymers were functionalized by an azo-coupling reaction to form the polymers with different degrees of functionalization and various heterocyclic sulfonamide groups. Ellipsometric measurements showed a decrease of the refractive index during illumination of thin polymer films with white light. The change of real part of the refractive index was in the range of 0.0033-0.0296 depending on the polymer kind and chromophore content. It was found that photocurrent was generated in the polymer films deposited onto indium tin oxide (ITO) glass plates. For the polyurethanes containing sulfathiazole groups in side chains the current density was up to 180 nA/cm{sup 2}. The formation of diffraction grating in the polymer films was easily achieved using linearly polarized laser light (532 nm) in a standard two beam coupling (TBC) system. The diffraction efficiency of the first diffraction beam was dependent on the chromophore content reaching ca. 12% for the derivatives of sulfamethoxazole.

  14. Synthesis and description of intermolecular interactions in new sulfonamide derivatives of tranexamic acid

    Science.gov (United States)

    Ashfaq, Muhammad; Arshad, Muhammad Nadeem; Danish, Muhammad; Asiri, Abdullah M.; Khatoon, Sadia; Mustafa, Ghulam; Zolotarev, Pavel N.; Butt, Rabia Ayub; Şahin, Onur

    2016-01-01

    Tranexamic acid (4-aminomethyl-cyclohexanecarboxylic acid) was reacted with sulfonyl chlorides to produce structurally related four sulfonamide derivatives using simple and environmental friendly method to check out their three-dimensional behavior and van der Walls interactions. The molecules were crystallized in different possibilities, as it is/after alkylation at its O and N atoms/along with a co-molecule. All molecules were crystallized in monoclinic crystal system with space group P21/n, P21/c and P21/a. X-ray studies reveal that the molecules stabilized themselves by different kinds of hydrogen bonding interactions. The molecules are getting connected through O-H⋯O hydrogen bonds to form inversion dimers which are further connected through N-H⋯O interactions. The molecules in which N and O atoms were alkylated showed non-classical interaction and generated centro-symmetric R22(24) ring motif. The co-crystallized host and guest molecules are connected to each other via O-H⋯O interactions to generate different ring motifs. By means of the ToposPro software an analysis of the topologies of underlying nets that correspond to molecular packings and hydrogen-bonded networks in structures under consideration was carried out.

  15. Multiresidue determination of fluoroquinolone, sulfonamide, trimethoprim, and chloramphenicol antibiotics in urban waters in China.

    Science.gov (United States)

    Peng, Xianzhi; Tan, Jianhua; Tang, Caiming; Yu, Yiyi; Wang, Zhendi

    2008-01-01

    A feasible method has been optimized to simultaneously determine multiclass antibiotic residues, including sulfonamides, fluoroquinolones, trimethoprim, and chloramphenicol in urban riverine water and wastewater by off-line solid phase extraction and high-performance liquid chromatography coupled with a diode-array ultraviolet detector and a fluorescence detector. Internal standard and standard addition methods were used in combination to identify and quantify these antibiotics to compensate for the matrix interference. The method quantification limits (MQLs) were determined to be 0.035 to 0.100 microg/L and 0.100 to 0.300 microg/L for the riverine water and wastewater, respectively. Recoveries of the investigated antibiotics ranged from 63 to 126%. Sulfamethoxazole was the most frequently detected antibiotic residue in Guangzhou section of the Major Pearl River, South China, with a maximum level of 0.510 microg/L. Fluoroquinolone antibiotics were relatively less detected with a maximum level of 0.459 microg/L. The maximum concentration of sulfamethoxazole reached 5.597 microg/L in the raw wastewater from a large-scale sewage treatment plant in Guangzhou city. Around 30% of sulfamethoxazole might survive the primary clarification and biotreatment processes in the sewage treatment plant. None of the investigated antibiotics have been found above MQLs in the final effluent after chlorine disinfection.

  16. The effect of miscellaneous oral dosage forms on the environmental pollution of sulfonamides in pig holdings.

    Science.gov (United States)

    Stahl, Jessica; Zessel, Katrin; Schulz, Jochen; Finke, Jan Henrik; Müller-Goymann, Christel Charlotte; Kietzmann, Manfred

    2016-04-01

    Due to antibiotic treatment of humans and animals, the prevalence of bacterial resistances increases worldwide. Especially in livestock farming, large quantities of faeces contaminated with antibiotics pose a risk of the carryover of the active ingredient to the environment. Accordingly, the aim of the present study was the evaluation of the benefit of different oral dosage forms (powder, pellets, granula) in pigs concerning the environmental pollution of sulfadiazine. Two subtherapeutic dosages were evaluated in powder mixtures to gain information about their potential to pollute the pig barn. Furthermore, a new group of pigs was kept in the stable after powder feeding of another pig group to determine the possible absorption of environmentally distributed antibiotics. Pigs were orally treated with three dosage forms. Simultaneously, sedimentation and airborne dust were collected and plasma and urine levels were determined. All formulations result in comparable plasma and urine levels, but massive differences in environmental pollution (powder > pellets, granula). Pigs housing in a contaminated barn exhibit traces of sulfadiazine in plasma and urine. Using pharmaceutical formulations like pellets or granula, the environmental pollution of sulfonamides can significantly be diminished due to massive dust reduction during feeding.

  17. Synthesis of piperazine sulfonamide analogs as diabetic-II inhibitors and their molecular docking study.

    Science.gov (United States)

    Taha, Muhammad; Irshad, Maryam; Imran, Syahrul; Chigurupati, Sridevi; Selvaraj, Manikandan; Rahim, Fazal; Ismail, Nor Hadiani; Nawaz, Faisal; Khan, Khalid Mohammed

    2017-12-01

    Piperazine Sulfonamide analogs (1-19) have been synthesized, characterized by different spectroscopic techniques and evaluated for α-amylase Inhibition. Analogs 1-19 exhibited a varying degree of α-amylase inhibitory activity with IC 50 values ranging in between 1.571 ± 0.05 to 3.98 ± 0.397 μM when compared with the standard acarbose (IC 50  = 1.353 ± 0.232 μM). Compound 1, 2, 3 and 7 showed significant inhibitory effects with IC 50 value 2.348 ± 0.444, 2.064 ± 0.04, 1.571 ± 0.05 and 2.118 ± 0.204 μM, respectively better than the rest of the series. Structure activity relationships were established. Molecular docking studies were performed to understand the binding interaction of the compounds. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Fate of sulfonamides, macrolides, and trimethoprim in different wastewater treatment technologies

    International Nuclear Information System (INIS)

    Goebel, Anke; McArdell, Christa S.; Joss, Adriano; Siegrist, Hansruedi; Giger, Walter

    2007-01-01

    The elimination of sulfonamides, macrolides and trimethoprim from raw wastewater was investigated in several municipal wastewater treatment plants. Primary treatment provided no significant elimination for the investigated substances. Similar eliminations were observed in the secondary treatment of two conventional activated sludge (CAS) systems and a fixed-bed reactor (FBR). Sulfamethoxazole, including the fraction present as N 4 -acetyl-sulfamethoxazole, was eliminated by approximately 60% in comparison to about 80% in a membrane bioreactor (MBR) independently of the solid retention time (SRT), indicating a positive correlation of the observed elimination to the organic substrate concentration. The elimination for macrolides and trimethoprim varied significantly between the different sampling campaigns in the two CAS systems and in the FBR. In the MBR, these analytes were eliminated up to 50% at SRT of 16 ± 2 and 33 ± 3 d. Trimethoprim, clarithromycin and dehydro-erythromycin showed a higher elimination of up to 90% at a SRT of 60-80 d indicating a correlation with reduced substrate loading (SL). Together with the high SRT, the SL may lead to an increased biodiversity of the active biomass, resulting in a broader range of degradation pathways available. Two investigated sand filters showed different elimination behavior. One led to a significant elimination of most macrolides (17-23%) and trimethoprim (74 ± 14%), while no elimination was observed in the other sand filter investigated

  19. Residual veterinary antibiotics in pig excreta after oral administration of sulfonamides.

    Science.gov (United States)

    Qiu, Jinrong; Zhao, Tao; Liu, Qingyun; He, Jinhua; He, Dechun; Wu, Genyi; Li, Yongtao; Jiang, Chengai; Xu, Zhencheng

    2016-04-01

    Sulfonamides (SAs) are applied widely as feed additives in the farming of livestock and poultry. It can lead to the excretion of large amounts of SAs in manure and result in persistent environmental pollution. We evaluated the fate of four SAs, sulfamerazine (SM1), sulfachloropyridazine (SCP), sulfadimoxine (SDM') and sulfaquinoxaline (SQ), from oral administration to excretion in urine and feces in pigs. The four SAs were added to homemade feed to make them reach the required concentration gradient, which were 0, 50 and 100 mg/kg (low, normal and high concentrations, respectively). In different treatments, excretions of the four SAs were 35.68-86.88 %. With regard to total excretion, the order was SQ > SCP > SM1 > SDM' for all treatments. The concentration of SAs in the feed had significant effects on the amount of the four SAs excreted every day. The concentration of SAs in feces and in the urine for different treatments was 15.03-26.55 and 14.54-69.22 %, respectively. In each treatment, excretions of SCP, SDM' and SQ in feces were lower than that in urine. The four SAs remained longer in urine than in feces. Excretions in urine and feces were lower if SAs were administered orally rather than by injection.

  20. Traceability of sulfonamide antibiotic treatment by immunochemical analysis of farm animal hair samples.

    Science.gov (United States)

    Adrian, Javier; Gratacós-Cubarsí, Marta; Sánchez-Baeza, Francisco; Garcia Regueiro, Jose-Antonio; Castellari, Massimo; Marco, M-Pilar

    2009-10-01

    The use of hair to trace use of unauthorized substances, therapeutic agents, or their misuse is becoming very attractive since residues can be detected for a long time after treatment. For this purpose, an indirect enzyme-linked immunosorbent assay (ELISA) has been evaluated for its capability to trace sulfonamide antibiotic treatment by analyzing cattle and pig hair samples. Pigmented and nonpigmented hair samples from control and sulfamethazine (SMZ)-treated pigs and calves were collected, extracted under different alkaline conditions, and analyzed by ELISA after just diluting the extracts with the assay buffer. Data analysis following the European recommendations for screening methods demonstrates that the ELISA can detect SMZ in hair samples with a limit of detection (90% of the zero dose (IC(90))) between 30 and 75 ng g(-1). The same samples have been analyzed by HPLC after a dual solid-phase extraction. The ELISA results matched very well those obtained by the chromatographic method, demonstrating that the immunochemical method can be used as a screening tool to trace animal treatments. Between the benefits of this method are the possibility to directly analyze hair extracts with sufficient detectability and its high-throughput capability. Preliminary validation data are reported using an experimental approach inspired on the Commission Decision 2002/657/EC criteria for screening methods.

  1. 42 CFR 447.506 - Authorized generic drugs.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Authorized generic drugs. 447.506 Section 447.506... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS PAYMENTS FOR SERVICES Payment for Drugs § 447.506 Authorized generic drugs. (a) Authorized generic drug defined. For the purposes of this subpart, an authorized generic drug...

  2. Perfluoroalkylated Derivatives of Diols and Triols. Selectivity in the Reaction of Primary and Secondary Hydroxy Groups with Perfluoroalkylepoxides. Hemocompatibility and Effect on Perfluorocarbon Emulsion

    Czech Academy of Sciences Publication Activity Database

    Církva, Vladimír; Polák, R.; Paleta, O.; Kodíček, K.; Forman, S.

    2002-01-01

    Roč. 67, č. 10 (2002), s. 1436-1448 ISSN 0010-0765 R&D Projects: GA ČR GA203/98/1174; GA MŠk LB98233 Keywords : perfluoroalkyl epoxides * fluoroalkylations * fluorophilic triols Subject RIV: CC - Organic Chemistry Impact factor: 0.848, year: 2002

  3. Sperm DNA integrity in relation to exposure to environmental perfluoroalkyl substances - a study of spouses of pregnant women in three geographical regions

    DEFF Research Database (Denmark)

    Specht, Ina Olmer; Hougaard, Karin; Spanò, Marcello

    2012-01-01

    Perfluoroalkyl substances (PFASs) can interfere with male reproductive function, but evidence in humans is limited. Six hundred four fertile men (199 from Greenland, 197 from Poland and 208 from Ukraine) were enrolled in the study. We measured four PFASs in serum (PFOS, PFOA, PFNA and PFHxS) and ...

  4. Perfluoroalkyl compounds in relation to life-history and reproductive parameters in bottlenose dolphins (Tursiops truncatus) from Sarasota Bay, Florida, USA

    NARCIS (Netherlands)

    Houde, M.; Balmer, B.C.; Brandsma, S.H.; Wells, R.S.; Rowles, T.K.; Solomon, K.R.; Muir, D.C.G.

    2006-01-01

    Perfluoroalkyl compounds (PFCs) were determined in plasma, milk, and urine of free-ranging bottlenose dolphins (Tursiops truncatus) from Sarasota Bay (FL, USA) during three winter and two summer capture-and-release programs (2002¿ 2005). Plasma and urine samples were extracted using an ion-pairing

  5. Perfluoroalkyl compounds in relation to life-history and reproductive parameters in bottlenose dolphins (Tursiops truncatus) from Sarasota Bay, Florida, U.S.A

    NARCIS (Netherlands)

    Houde, Magali; Balmer, Brian C; Brandsma, Sicco; Wells, Randall S; Rowles, Teri K; Solomon, Keith R; Muir, Derek C G

    Perfluoroalkyl compounds (PFCs) were determined in plasma, milk, and urine of free-ranging bottlenose dolphins (Tursiops truncatus) from Sarasota Bay (FL, USA) during three winter and two summer capture-and-release programs (2002-2005). Plasma and urine samples were extracted using an ion-pairing

  6. 76 FR 54507 - Proposed Generic Communication; Draft NRC Generic Letter 2011-XX: Seismic Risk Evaluations for...

    Science.gov (United States)

    2011-09-01

    ... NUCLEAR REGULATORY COMMISSION [NRC-2011-0204] Proposed Generic Communication; Draft NRC Generic... functions. SSCs in operating nuclear power plants are designed either in accordance with, or have been... nuclear reactors. The background information relevant to this GL includes the individual plant...

  7. [Analysis of generic drug supply in France].

    Science.gov (United States)

    Taboulet, F; Haramburu, F; Latry, Ph

    2003-09-01

    The list of generic medicines (LGM), published since 1997 by the Agence Française de Sécurité Sanitaire des Produits de Santé (AFFSSaPS), the French Medicine Agency, concerns a special part of the medicines reimbursed by the National Health Insurance (Social Security). The objectives of the present study were: i) to describe the components of this list, based on pharmaceutical, economical and therapeutic characteristics, ii) to study differences between generic and reference products (formulations, excipients, prices, etc.), iii) to analyze information on excipients provided to health care professionals. The 21st version of the LGM (April 2001) was used. Therapeutic value was retrieved from the 2001 AFSSaPS report on the therapeutic value of 4490 reimbursed medicines. Information on excipients in the LGM and the Vidal dictionary (reference prescription book in France) was compared. The products included in the LGM represent 20% of all reimbursed medicines. The mean price differences between generics and their reference products vary between 30 and 50% for more than two thirds of the generic groups. The therapeutic value of the products of the LGM was judged important in 71% of cases (vs 63% for the 4409 assessed medicines) and insufficient in 13% of cases (vs 19%). Information on excipients is often missing and sometimes erroneous. Although the LGM is regularly revised and thus the generic market in perpetual change, the 2001 cross description of this pharmaceutical market provides much informations and raises some concern.

  8. Uptake and elimination kinetics of perfluoroalkyl substances in submerged and free-floating aquatic macrophytes: Results of mesocosm experiments with Echinodorus horemanii and Eichhornia crassipes.

    Science.gov (United States)

    Pi, N; Ng, J Z; Kelly, B C

    2017-06-15

    Studies investigating the bioaccumulation behavior of perfluoroalkyl substances (PFASs) in aquatic macrophytes are limited. The present study involved controlled mesocosm experiments to assess uptake and elimination rate constants (k u, k e ), bioconcentration factors (BCFs) and translocation factors (TFs) of several perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkane sulfonic acids (PFSAs) in two aquatic plant species, including one submerged species (Echinodorus horemanii) and one free-floating species (Eichhornia crassipes). The results indicated all PFASs were readily accumulated in these aquatic macrophytes. k u and BCFs increased with increasing perfluoroalkyl chain length. For PFCAs and PFSAs with identical perfluoroalkyl chain length, the corresponding PFSA exhibited higher bioaccumulation potential. On a whole-plant basis, the bioaccumulation potential of PFASs in submerged and free-floating macrophytes were comparable, indicating sorption to plant biomass is similar in the different species. Conversely, when considering accumulation in foliage, BCFs in the free-floating macrophyte were substantially lower compared to submerged species, especially for longer-chain PFASs. Compounds with shorter perfluoroalkyl chain length (PFBS, PFPeA and PFHxA) exhibited preferential translocation to leaf tissue (TFs >1). BCFs exhibited a sigmoidal relationship with pefluoroalkyl chain length, membrane-water distribution coefficients (D mw ), protein-water distribution coefficients (D pw ) and organic-water partition coefficients (K oc ). For these trends, maximum BCF values were exhibited by long-chain PFCAs, with a log D mw , log D pw and log K oc of 6.47, 5.72 and 5.04, respectively. These findings are useful for future design and implementation of phytoremediation systems, as well for future develop of mechanistic models for predicting the environmental fate and distribution of these contaminants of concern. Copyright © 2017. Published by Elsevier Ltd.

  9. Environmental Fate and Transport of Poly- and Perfluoroalkyl Substances at Aqueous Film-Forming Foam Impacted Sites

    Science.gov (United States)

    Higgins, C.

    2017-12-01

    Poly and perfluoroalkyl substances (PFASs) are constituents in aqueous film-forming foam (AFFF) used to extinguish fuel fires. Substantially elevated PFAS groundwater concentrations have been observed at firefighter protection training areas, where co-contaminants such as chlorinated solvents and fuel hydrocarbons are also commonly present. Research into the fate and transport potential of PFASs at AFFF-impacted sites will be presented, with a particular focus on how co-contaminants and co-contaminant remediation technologies may alter the composition and transport behavior of PFASs at these sites. A detailed analysis of data collected from a U.S. Air Force site (Ellsworth Air Force Base, South Dakota) indicates that that conversion of polyfluoroalkyl chemicals to perfluoroalkyl acids (PFAAs) in situ due to natural and enhanced remediation of petroleum hydrocarbons. In addition, bench-scale studies examining the effects of various chemical oxidants, typically employed via in situ chemical oxidation (ISCO), indicates that oxidation-based remediation technologies have the potential to alter the release and composition of PFASs in AFFF-impacted source zones. Future challenges in addressing PFAS contamination will be discussed, particularly with respect to closing the mass balance on PFAAs and their precursors at AFFF-impacted sites.

  10. Association of Perfluoroalkyl Substances, Bone Mineral Density, and Osteoporosis in the U.S. Population in NHANES 2009-2010.

    Science.gov (United States)

    Khalil, Naila; Chen, Aimin; Lee, Miryoung; Czerwinski, Stefan A; Ebert, James R; DeWitt, Jamie C; Kannan, Kurunthachalam

    2016-01-01

    Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), are detectable in the serum of 95% of the U.S. Considering the role of PFASs as endocrine disruptors, we examined their relationships with bone health. The association between serum PFAS concentration and bone mineral density at total femur (TFBMD), femoral neck (FNBMD), lumbar spine (LSBMD), and physician-diagnosed osteoporosis was assessed in 1,914 participants using data from the National Health and Nutritional Examination Survey 2009-2010. The mean age of the participants was 43 years. Men had higher serum PFAS concentrations than women (p PFAS concentrations were associated with lower bone mineral density, which varied according to the specific PFAS and bone site assessed. Most associations were limited to women. Osteoporosis in women was also associated with PFAS exposure, based on a small number of cases. Khalil N, Chen A, Lee M, Czerwinski SA, Ebert JR, DeWitt JC, Kannan K. 2016. Association of perfluoroalkyl substances, bone mineral density, and osteoporosis in the U.S. population in NHANES 2009-2010. Environ Health Perspect 124:81-87; http://dx.doi.org/10.1289/ehp.1307909.

  11. Treatment of poly- and perfluoroalkyl substances in U.S. full-scale water treatment systems.

    Science.gov (United States)

    Appleman, Timothy D; Higgins, Christopher P; Quiñones, Oscar; Vanderford, Brett J; Kolstad, Chad; Zeigler-Holady, Janie C; Dickenson, Eric R V

    2014-03-15

    The near ubiquitous presence of poly- and perfluoroalkyl substances (PFASs) in humans has raised concerns about potential human health effects from these chemicals, some of which are both extremely persistent and bioaccumulative. Because some of these chemicals are highly water soluble, one major pathway for human exposure is the consumption of contaminated drinking water. This study measured concentrations of PFASs in 18 raw drinking water sources and 2 treated wastewater effluents and evaluated 15 full-scale treatment systems for the attenuation of PFASs in water treatment utilities throughout the U.S. A liquid-chromatography tandem mass-spectrometry method was used to enable measurement of a suite of 23 PFASs, including perfluorocarboxylic acids (PFCAs) and perfluorosulfonic acids (PFSAs). Despite the differences in reporting levels, the PFASs that were detected in >70% of the source water samples (n = 39) included PFSAs, perfluorobutane sulfonic acid (74%), perfluorohexane sulfonic acid (79%), and perfluorooctane sulfonic acid (84%), and PFCAs, perfluoropentanoic acid (74%), perfluorohexanoic acid (79%), perfluoroheptanoic acid (74%), and perfluorooctanoic acid (74%). More importantly, water treatment techniques such as ferric or alum coagulation, granular/micro-/ultra- filtration, aeration, oxidation (i.e., permanganate, ultraviolet/hydrogen peroxide), and disinfection (i.e., ozonation, chlorine dioxide, chlorination, and chloramination) were mostly ineffective in removing PFASs. However, anion exchange and granular activated carbon treatment preferably removed longer-chain PFASs and the PFSAs compared to the PFCAs, and reverse osmosis demonstrated significant removal for all the PFASs, including the smallest PFAS, perfluorobutanoic acid. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. Spatiotemporal distribution and mass loadings of perfluoroalkyl substances in the Yangtze River of China.

    Science.gov (United States)

    Pan, Chang-Gui; Ying, Guang-Guo; Zhao, Jian-Liang; Liu, You-Sheng; Jiang, Yu-Xia; Zhang, Qian-Qian

    2014-09-15

    A systematic investigation into contamination profiles of eighteen perfluoroalkyl substances (PFASs) in both surface water and sediments of Yangtze River was carried out by using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in summer and winter of 2013. The total concentrations of the PFASs in the water and sediment of Yangtze River ranged from 2.2 to 74.56 ng/L and 0.05 to 1.44 ng/g dry weights (dw), respectively. The PFAS concentrations were correlated to some selected water quality parameters such as pH, total phosphorus (TP), total nitrogen (TN) and conductivity in water, and some sediment properties, such as total organic carbon (TOC), TP, and TN in sediment. The monitoring results for the water and sediment samples showed no obvious seasonal variations. Among the selected 18 PFASs, perfluorooctanoic acid (PFOA) was the dominant PFAS compound found both in water and sediment for the two seasons with its maximum concentration of 18.03 ng/L in water and 0.72 ng/g in sediment, followed by perfluorobutane sulfonic acid (PFBS) with its maximum concentration of 41.9 ng/L in water in Wuhan, whereas the lowest concentrations of PFASs were observed at Poyang lake. The annual loadings of PFOA, perfluorohexanoic acid (PFHxA), PFBS, perfluorooctane sulfonic acid (PFOS) and the total PFASs in the Yangtze River were 6.8 tons, 2.2 tons, 8.2 tons, 0.88 tons, and 20.7 tons, respectively. Wuhan and Er'zhou of Hubei contributed the most amounts of PFASs into the Yangtze River. A correlation was found between some PFASs, for example PFBS and PFOS, which suggests that both of these PFASs originate from common sources in the region. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Short communication: Monitoring the presence of perfluoroalkyl substances in Italian cow milk.

    Science.gov (United States)

    Barbarossa, Andrea; Gazzotti, Teresa; Zironi, Elisa; Serraino, Andrea; Pagliuca, Giampiero

    2014-01-01

    Perfluoroalkyl substances (PFAS) are fully fluorinated compounds widely used during the last 60 yr in the production of multiple industrial and consumer applications, such as food packaging, nonstick cookware, cleaning agents, and many more. These emerging contaminants have recently become of concern for human health because of their potential negative effects. The risk of exposure to PFAS for humans is mainly related to diet, and the increasing interest in food safety has led the European Commission to call Member States to monitor these contaminants in food matrices. The purpose of the present work was to perform the first monitoring on the presence of perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), the 2 main and most widely investigated molecules of this family, in cow milk commercially available in Italy. We used an analytical protocol consisting of liquid-liquid extraction followed by 2 purification steps through solid-phase extraction cartridges and injection on an ultra-performance liquid chromatography-tandem mass spectroscopy system. The analysis of 67 samples of different types of cow milk from Italy demonstrated that contamination by PFOS was often present, although at relatively low concentrations (up to 97 ng/L), whereas PFOA was rarely found. On the basis of these results and data reported in the literature on this matrix, milk does not seem to be a major source of PFAS compared with other food categories such as fish and seafood. However, variability among different types of milk must be taken into account, and surveys of milk-derived products would be helpful to better define the risk for consumers. Copyright © 2014 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Temporal trends (1999–2010) of perfluoroalkyl acids in commonly consumed food items

    International Nuclear Information System (INIS)

    Johansson, Jana H.; Berger, Urs; Vestergren, Robin; Cousins, Ian T.; Bignert, Anders; Glynn, Anders; Darnerud, Per Ola

    2014-01-01

    The aim of this study was to determine how dietary exposure to PFAAs has changed over the period when major production changes occurred. Archived samples (1999–2010) of eggs, milk and farmed rainbow trout were analyzed by ultra performance liquid chromatography coupled to tandem mass spectrometry. Statistically significant decreasing trends were observed for concentrations of perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS) in fish (p < 0.002 and p < 0.032, respectively) and eggs (p < 0.001 for both compounds). Concentrations of PFOS in fish and eggs decreased by a factor of 10 and 40, respectively. In eggs there was also a statistically significant decreasing trend in concentrations of perfluorooctanoic acid (PFOA). The results of this study demonstrate that PFAA concentrations in food items from agricultural food chains and aquatic food chains close to sources respond rapidly to changes in environmental emissions. Implications for the overall understanding of human exposure are discussed. - Highlights: • Food items sampled yearly (1999–2010) were analyzed for perfluoroalkyl acids. • Significantly declining trends were observed for PFOS and PFHxS in farmed fish and eggs. • In eggs, an additional significant decreasing trend was found for PFOA. • A decrease in human dietary exposure to PFHxS, PFOS and PFOA is suggested. - Concentrations of PFOS in farmed fish and in hen's eggs decreased between 1999 and 2010. Furthermore, we observed decreasing trends of PFOA in eggs and PFHxS in fish

  15. Occurrence, fluxes and sources of perfluoroalkyl substances with isomer analysis in the snow of northern China

    International Nuclear Information System (INIS)

    Shan, Guoqiang; Chen, Xinwei; Zhu, Lingyan

    2015-01-01

    Highlights: • Relatively high levels of PFASs were present in the snow in northern China in 2013. • Particulate bound PFASs contributed 21.5–56.2% to the total PFASs in snow. • Particulate matters are vital for PFASs transport and deposition in urban atmosphere. • Partitioning of PFASs between particulate and dissolved phase was related to carbon chain length. • Isomer profiles in snow suggested that airborne PFASs were mainly from direct release. - Abstract: In this study, perfluoroalkyl substances (PFASs) and the isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) were analyzed in fresh snow samples collected from 19 cities in northern China, 2013. The levels of total PFASs in the snow samples were 33.5–229 ng/L, suggesting heavy atmospheric pollution of PFASs in northern China. PFOA (9.08–107 ng/L), PFOS (3.52–54.3 ng/L), perfluoroheptanoate (PFHpA) (3.66–44.8 ng/L), and perfluorohexanoate (PFHxA) (3.21–23.6 ng/L) were predominant with a summed contribution of 82% to the total PFASs. The particulate matters (PMs) associated PFASs contributed 21.5–56.2% to the total PFASs in the snow, suggesting PMs are vital for the transport and deposition of airborne PFASs. Partitioning of PFASs between PM and dissolved phases was dependent on the carbon chain length and end functional groups. Isomer profiles of PFOA and PFOS in the snow were in agreement with the signature of the historical 3 M electrochemical fluorination (ECF) products, suggesting that the ECF products were still produced and used in China. Further source analysis showed that the airborne PFASs in urban area were mainly due to direct release rather than degradation of their precursors.

  16. Impacts of daily intakes on the isomeric profiles of perfluoroalkyl substances (PFASs) in human serum.

    Science.gov (United States)

    Shan, Guoqiang; Wang, Zhi; Zhou, Lianqiu; Du, Pin; Luo, Xiaoxiao; Wu, Qiannian; Zhu, Lingyan

    2016-01-01

    Perfluoroalkyl substances (PFASs) have been well studied in human daily intake for assessment of potential health risks. However, little is known about the isomeric compositions of PFASs in daily intake and their impacts on isomeric profiles in humans. In this study, we investigated the occurrence of PFASs with isomeric analysis in various human exposure matrices including foodstuffs, tap water and indoor dust. Perfluorooctanesulfonate (PFOS) and/or perfluorooctanoate (PFOA) were predominant in these exposure matrices collected in Tianjin, China. In fish and meat, linear (n-) PFOA was enriched with a percentage of 92.2% and 99.6%, respectively. Although n-PFOS was higher in fish (84.8%) than in technical PFOS (ca. 70%), it was much lower in meat (63.1%) and vegetables (58.5%). Dietary intake contributed >99% of the estimated daily intake (EDI) for the general population. The isomeric profiles of PFOA and PFOS in human serum were predicted based on the EDI and a one-compartment, first-order pharmacokinetic model. The isomeric percentage of n-PFOA in the EDI (98.6%) was similar to that in human serum (predicted: 98.2%, previously measured: 99.7%) of Tianjin residents. The results suggest direct PFOA intake plays an important role in its isomeric compositions in humans. For PFOS, the predicted n-PFOS (69.3%) was much higher than the previously measured values (59.2%) in human serum. This implies that other factors, such as indirect exposure to PFOS precursors and multiple excretion pathways, may contribute to the lower percentage of n-PFOS in humans than of technical PFOS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The use of carbon adsorbents for the removal of perfluoroalkyl acids from potable reuse systems.

    Science.gov (United States)

    Inyang, Mandu; Dickenson, Eric R V

    2017-10-01

    Bench- and pilot-scale sorption tests were used to probe the performance of several biochars at removing perfluoroalkyl acids (PFAA) from field waters, compared to granular activated carbon (GAC). Screening tests using organic matter-free water resulted in hardwood (HWC) (K d  = 41 L g -1 ) and pinewood (PWC) (K d  = 49 L g -1 ) biochars having the highest perfluorooctanoic acid (PFOA) removal performance that was comparable to bituminous coal GAC (K d  = 41 L g -1 ). PWC and HWC had a stronger affinity for PFOA sorbed in Lake Mead surface water (K F  = 11 mg (1-n) L n g -1 ) containing a lower (2 mg L -1 ) dissolved organic carbon (DOC) concentration than in a tertiary-filtered wastewater (K F  = 8 mg (1-n) L n g -1 ) with DOC of 4.9 mg L -1 . A pilot-scale study was performed using three parallel adsorbers (GAC, anthracite, and HWC biochar) treating the same tertiary-filtered wastewater. Compared to HWC, and anthracite, GAC was the most effective in mitigating perfluoropentanoic acid (PFPnA), perfluorohexanoic acid (PHxA), PFOA, perfluorooctane sulfonic acid (PFOS), and DOC (45-67% removed at 4354 bed volumes) followed by HWC, and then anthracite. Based on bench- and pilot-scale results, shorter-chain PFAA [perfluorobutanoic acid (PFBA), PFPnA, or PFHxA] were more difficult to remove with both biochar and GAC than the longer-chain, PFOS and PFOA. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Biomagnification and tissue distribution of perfluoroalkyl substances (PFASs) in market-size rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Goeritz, Ina; Falk, Sandy; Stahl, Thorsten; Schäfers, Christoph; Schlechtriem, Christian

    2013-09-01

    The present study investigated the biomagnification potential as well as the substance and tissue-specific distribution of perfluoroalkyl substances (PFASs) in market-size rainbow trout (Oncorhynchus mykiss). Rainbow trout with an average body weight of 314 ± 21 g were exposed to perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) in the diet for 28 d. The accumulation phase was followed by a 28-d depuration phase, in which the test animals were fed with nonspiked trout feed. On days 0, 7, 14, 28, 31, 35, 42, and 56 of the present study, fish were sampled from the test basin for PFAS analysis. Biomagnification factors (BMFs) for all test compounds were determined based on a kinetic approach. Distribution factors were calculated for each test compound to illustrate the disposition of PFASs in rainbow trout after 28 d of exposure. Dietary exposure of market-size rainbow trout to PFASs did not result in biomagnification; BMF values were calculated as 0.42 for PFOS, >0.23 for PFNA, >0.18 for PFHxS, >0.04 for PFOA, and >0.02 for PFBS, which are below the biomagnification threshold of 1. Liver, blood, kidney, and skin were identified as the main target tissues for PFASs in market-size rainbow trout. Evidence was shown that despite relative low PFAS contamination, the edible parts of the fish (the fillet and skin) can significantly contribute to the whole-body burden. Copyright © 2013 SETAC.

  19. Temporal variations of perfluoroalkyl substances and polybrominated diphenyl ethers in alpine snow

    International Nuclear Information System (INIS)

    Kirchgeorg, Torben; Dreyer, Annekatrin; Gabrieli, Jacopo; Kehrwald, Natalie; Sigl, Michael; Schwikowski, Margit

    2013-01-01

    The occurrence and temporal variation of 18 perfluoroalkyl substances (PFASs) and 8 polybrominated diphenyl ethers (PBDEs) in the European Alps was investigated in a 10 m shallow firn core from Colle Gnifetti in the Monte Rosa Massif (4455 m above sea level). The firn core encompasses the years 1997–2007. Firn core sections were analyzed by liquid chromatography–tandem mass spectrometry (PFASs) and gas chromatography–mass spectrometry (PBDEs). We detected 12 PFASs and 8 PBDEs in the firn samples. Perfluorobutanoic acid (PFBA; 0.3–1.8 ng L −1 ) and perfluorooctanoic acid (PFOA; 0.2–0.6 ng L −1 ) were the major PFASs while BDE 99 ( −1 ) and BDE 47 (n.d.–2.6 ng L −1 ) were the major PBDEs. This study demonstrates the occurrence of PFASs and PBDEs in the European Alps and provides the first evidence that PFASs compositions may be changing to PFBA-dominated compositions. -- Highlights: •PFASs and PBDEs were detected in low ng L −1 concentrations in an Alpine firn core. •BDE 47, BDE 99 and BDE 209 are the dominating PBDEs. •PFOA, PFNA and PFBA are the major PFASs. •We demonstrate a change in the PFASs composition. •Atmospheric degradation of volatile precursor might be the main source for >C8 PFCAs. -- PFAS and PBDE concentrations in European Alpine snow provide information about the occurrence, accumulation and recent changes of these persistent organic pollutants in Alpine regions

  20. A national discharge load of perfluoroalkyl acids derived from industrial wastewater treatment plants in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee-Young; Seok, Hyun-Woo [Department of Civil and Environmental Engineering, Pusan National University, Busan 46241 (Korea, Republic of); Kwon, Hye-Ok; Choi, Sung-Deuk [School of Urban and Environmental Engineering, Ulsan National Institute of Science and Technology, Ulsan 44919 (Korea, Republic of); Seok, Kwang-Seol [Chemical Research Division, National Institute of Environmental Research, Incheon 22689 (Korea, Republic of); Oh, Jeong Eun [Department of Civil and Environmental Engineering, Pusan National University, Busan 46241 (Korea, Republic of)

    2016-09-01

    Levels of 11 perfluoroalkyl acids (PFAAs), including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), were measured in wastewater (influent and effluent) and sludge samples collected from 25 industrial wastewater treatment plants (I-WWTPs) in five industrial sectors (chemicals, electronics, metals, paper, and textiles) in South Korea. The highest ∑{sub 11}PFAAs concentrations were detected in the influent and effluent from the paper (median: 411 ng/L) and textile (median: 106 ng/L) industries, and PFOA and PFOS were the predominant PFAAs (49–66%) in wastewater. Exceptionally high levels of PFAAs were detected in the sludge associated with the electronics (median: 91.0 ng/g) and chemical (median: 81.5 ng/g) industries with PFOS being the predominant PFAA. The discharge loads of 11 PFAAs from I-WWTP were calculated that total discharge loads for the five industries were 0.146 ton/yr. The textile industry had the highest discharge load with 0.055 ton/yr (PFOA: 0.039 ton/yr, PFOS: 0.010 ton/yr). Municipal wastewater contributed more to the overall discharge of PFAAs (0.489 ton/yr) due to the very small industrial wastewater discharge compared to municipal wastewater discharge, but the contribution of PFAAs from I-WWTPs cannot be ignored. - Highlights: • 11 PFAAs in wastewater and sludge from 5 industrial sectors were investigated. • PFOA and PFOS were the dominant in wastewater while PFOS was predominant in sludge. • The total discharge loads from 5 industrial sectors 0.146 ton/yr. • The textile industry showed the highest discharge load with 0.055 ton/yr.

  1. Perfluoroalkylated substances (PFASs) in home and commercially produced chicken eggs from the Netherlands and Greece.

    Science.gov (United States)

    Zafeiraki, Effrosyni; Costopoulou, Danae; Vassiliadou, Irene; Leondiadis, Leondios; Dassenakis, Emmanouil; Hoogenboom, Ron L A P; van Leeuwen, Stefan P J

    2016-02-01

    Dietary intake is a major route of human exposure to perfluoroalkylated substances (PFASs). However, the available information on PFAS levels in food, including chicken eggs, is limited. In the present study, home produced and commercially produced eggs (organic, battery and free range eggs) were collected from the Netherlands (n = 95) and Greece (n = 76). The egg yolks were analysed for 11 PFASs by liquid chromatography-tandem mass spectrometry using isotope dilution. PFAS levels in yolk were higher in home produced eggs from the Netherlands (median 3.1, range eggs collected from supermarkets. In these eggs, all PFAS levels were below the LOQ of 0.5 ng g(-1), except for a small amount of perfluorooctane sulfonate (PFOS) in 1 sample in each country (1.1 ng g(-1) and 0.9 ng g(-1) for the Netherlands and Greece respectively). PFOS was the predominant PFAS, making up on average 85% of ∑PFASs. The highest PFOS concentration was detected in a Dutch home produced egg sample (24.8 ng g(-1)). The contamination pattern was similar in both countries with the long-chain PFASs (C ≥ 8) being most frequently detected, while short-chain PFASs were rarely found. The most likely cause of the contamination of home produced eggs is ingestion of soil through pecking. Although regular consumption of home produced eggs will lead to an increased PFOS exposure, it is not expected that it will lead to exceedance of the tolerable daily intake established by EFSA. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Occurrence, fluxes and sources of perfluoroalkyl substances with isomer analysis in the snow of northern China

    Energy Technology Data Exchange (ETDEWEB)

    Shan, Guoqiang; Chen, Xinwei; Zhu, Lingyan, E-mail: zhuly@nankai.edu.cn

    2015-12-15

    Highlights: • Relatively high levels of PFASs were present in the snow in northern China in 2013. • Particulate bound PFASs contributed 21.5–56.2% to the total PFASs in snow. • Particulate matters are vital for PFASs transport and deposition in urban atmosphere. • Partitioning of PFASs between particulate and dissolved phase was related to carbon chain length. • Isomer profiles in snow suggested that airborne PFASs were mainly from direct release. - Abstract: In this study, perfluoroalkyl substances (PFASs) and the isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) were analyzed in fresh snow samples collected from 19 cities in northern China, 2013. The levels of total PFASs in the snow samples were 33.5–229 ng/L, suggesting heavy atmospheric pollution of PFASs in northern China. PFOA (9.08–107 ng/L), PFOS (3.52–54.3 ng/L), perfluoroheptanoate (PFHpA) (3.66–44.8 ng/L), and perfluorohexanoate (PFHxA) (3.21–23.6 ng/L) were predominant with a summed contribution of 82% to the total PFASs. The particulate matters (PMs) associated PFASs contributed 21.5–56.2% to the total PFASs in the snow, suggesting PMs are vital for the transport and deposition of airborne PFASs. Partitioning of PFASs between PM and dissolved phases was dependent on the carbon chain length and end functional groups. Isomer profiles of PFOA and PFOS in the snow were in agreement with the signature of the historical 3 M electrochemical fluorination (ECF) products, suggesting that the ECF products were still produced and used in China. Further source analysis showed that the airborne PFASs in urban area were mainly due to direct release rather than degradation of their precursors.

  3. Drinking water contamination from perfluoroalkyl substances (PFAS): an ecological mortality study in the Veneto Region, Italy.

    Science.gov (United States)

    Mastrantonio, Marina; Bai, Edoardo; Uccelli, Raffaella; Cordiano, Vincenzo; Screpanti, Augusto; Crosignani, Paolo

    2018-02-01

    Perfluoroalkyl substances (PFAS), a heterogeneous group of highly stable man-made chemicals, have been widely used since 1960s and can be detected almost ubiquitously in all environmental matrices. In Italy, on January 2014, drinking water contamination in an area of the Veneto Region was detected mainly due to the drain of fluorinated chemicals by a manufacturing company operating since 1964. The present ecological mortality study was aimed at comparing mortality for some causes of death selected on the basis of previous reported associations, during the period 1980-2013, in municipalities with PFAS contaminated and uncontaminated drinking water on the basis of the levels indicated by the Italian National Health Institute (ISS). Sex-specific number, standardized mortality rates and rate ratios (RR) for PFAS contaminated and uncontaminated areas were computed for each cause of death through the ENEA epidemiological database. In both sexes, statistically significant RRs were detected for all causes mortality, diabetes, cerebrovascular diseases, myocardial infarction and Alzheimer's disease. In females, RRs significantly higher than 1.0 were also observed for kidney and breast cancer, and Parkinson's disease. Increased risk, although not statistically significant, was observed for bladder cancer in both sexes, and for testicular cancer, pancreatic cancer and leukemia in males only. Higher mortality levels for some causes of death, possibly associated with PFAS exposure, were detected in contaminated municipalities in comparison with uncontaminated ones with similar socioeconomic status and smoking habits. These results warrant further individual level analytic studies to delineate casual associations. © The Author 2017. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

  4. Changes in markers of liver function in relation to changes in perfluoroalkyl substances - A longitudinal study.

    Science.gov (United States)

    Salihovic, Samira; Stubleski, Jordan; Kärrman, Anna; Larsson, Anders; Fall, Tove; Lind, Lars; Lind, P Monica

    2018-08-01

    While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent. The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data. We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and γ-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels. The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers β BILIRUBIN  = -1.56, 95% confidence interval (CI) -1.93 to -1.19, β ALT  = 0.04, 95% CI 0.03-0.06, and β ALP  = 0.11, 95% CI 0.06-0.15. Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population. Copyright © 2018 Elsevier Ltd. All rights reserved.

  5. Human exposure to perfluoroalkyl substances near a fluorochemical industrial park in China.

    Science.gov (United States)

    Bao, Jia; Liu, Li; Wang, Xin; Jin, Yi-He; Dong, Guang-Hui

    2017-04-01

    Severe perfluoroalkyl substance (PFAS) contaminations have been observed in both surface water and groundwater in the vicinity of Fuxin, China, over the past years, attributing to the fast-growing fluorochemical industries locally. However, little is known about the overall daily intake of PFAS contaminations by Fuxin residents recently. In the present study, ten target PFAS analytes in the blood serum samples collected from 100 non-occupationally exposed healthy residents in Fuxin, with an average age of 47.6 years, together with 14 drinking water samples obtained from the public water system (PWS) of Fuxin were analyzed via high-performance liquid chromotography-tandem mass spectrometry (HPLC-MS/MS). As the dominant PFAS contaminant, the serum concentrations of perfluorooctanoic acid (PFOA) in Fuxin residents ranged between <0.05 and 160 ng/mL, with a median concentration of 9.4 ng/mL, which was higher than those reported previously for Fuxin and other areas worldwide. In drinking water samples, PFOA had a median value of 8.5 ng/L, ranging from 7.7 to 8.8 ng/L. Based upon the simplified one-compartment pharmacokinetic model, the total daily intake of PFOA for individuals residing in Fuxin ranged from 0.30 to 1.76 ng/kg bw/day, with a median of 0.79 ng/kg bw/day; furthermore, daily consumption of drinking water from the PWS in Fuxin appeared to contribute 35% of overall PFOA burden in local residents, which was approximately 3-fold higher compared to that estimated for Fuxin residents in 2009.

  6. Perfluoroalkyl substance serum concentrations and immune response to FluMist vaccination among healthy adults.

    Science.gov (United States)

    Stein, Cheryl R; Ge, Yongchao; Wolff, Mary S; Ye, Xiaoyun; Calafat, Antonia M; Kraus, Thomas; Moran, Thomas M

    2016-08-01

    Perfluoroalkyl substances (PFAS) were shown to be immunotoxic in laboratory animals. There is some epidemiological evidence that PFAS exposure is inversely associated with vaccine-induced antibody concentration. We examined immune response to vaccination with FluMist intranasal live attenuated influenza vaccine in relation to four PFAS (perfluorooctanoate, perfluorononanoate, perfluorooctane sulfonate, perfluorohexane sulfonate) serum concentrations among 78 healthy adults vaccinated during the 2010-2011 influenza season. We measured anti-A H1N1 antibody response and cytokine and chemokine concentrations in serum pre-vaccination, 3 days post-vaccination, and 30 days post-vaccination. We measured cytokine, chemokine, and mucosal IgA concentration in nasal secretions 3 days post-vaccination and 30 days post-vaccination. Adults with higher PFAS concentrations were more likely to seroconvert after FluMist vaccination as compared to adults with lower PFAS concentrations. The associations, however, were imprecise and few participants seroconverted as measured either by hemagglutination inhibition (9%) or immunohistochemical staining (25%). We observed no readily discernable or consistent pattern between PFAS concentration and baseline cytokine, chemokine, or mucosal IgA concentration, or between PFAS concentration and change in these immune markers between baseline and FluMist-response states. The results of this study do not support a reduced immune response to FluMist vaccination among healthy adults in relation to serum PFAS concentration. Given the study's many limitations, however, it does not rule out impaired vaccine response to other vaccines or vaccine components in either children or adults. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Perfluoroalkyl substances and time to pregnancy in couples from Greenland, Poland and Ukraine.

    Science.gov (United States)

    Jørgensen, Kristian T; Specht, Ina O; Lenters, Virissa; Bach, Cathrine C; Rylander, Lars; Jönsson, Bo A G; Lindh, Christian H; Giwercman, Aleksander; Heederik, Dick; Toft, Gunnar; Bonde, Jens Peter

    2014-12-22

    Perfluoroalkyl substances (PFAS) are suggested to affect human fecundity through longer time to pregnancy (TTP). We studied the relationship between four abundant PFAS and TTP in pregnant women from Greenland, Poland and Ukraine representing varying PFAS exposures and pregnancy planning behaviors. We measured serum levels of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS) and perfluorononanoic acid (PFNA) in 938 women from Greenland (448 women), Poland (203 women) and Ukraine (287 women). PFAS exposure was assessed on a continuous logarithm transformed scale and in country-specific tertiles. We used Cox discrete-time models and logistic regression to estimate fecundability ratios (FRs) and infertility (TTP >13 months) odds ratios (ORs), respectively, and 95% confidence intervals (CI) according to PFAS levels. Adjusted analyses of the association between PFAS and TTP were done for each study population and in a pooled sample. Higher PFNA levels were associated with longer TTP in the pooled sample (log-scale FR = 0.80; 95% CI 0.69-0.94) and specifically in women from Greenland (log-scale FR = 0.72; 95% CI 0.58-0.89). ORs for infertility were also increased in the pooled sample (log-scale OR = 1.53; 95% CI 1.08-2.15) and in women from Greenland (log-scale OR = 1.97; 95% CI 1.22-3.19). However, in a sensitivity analysis of primiparous women these associations could not be replicated. Associations with PFNA were weaker for women from Poland and Ukraine. PFOS, PFOA and PFHxS were not consistently associated with TTP. Findings do not provide consistent evidence that environmental exposure to PFAS is impairing female fecundity by delaying time taken to conceive.

  8. Neurotoxic effects of perfluoroalkylated compounds: mechanisms of action and environmental relevance.

    Science.gov (United States)

    Mariussen, Espen

    2012-09-01

    Perfluoroalkylated compounds (PFCs) are used in fire-fighting foams, treatment of clothes, carpets and leather products, and as lubricants, pesticides, in paints and medicine. Recent developments in chemical analysis have revealed that fluorinated compounds have become ubiquitously spread and are regarded as a potential threats to the environment. Due to the carbon-fluorine bond, which has a very high bond strength, these chemicals are extremely persistent towards degradation and some PFCs have a potential for bioaccumulation in organisms. Of particular concern has been the developmental toxicity of PFOS and PFOA, which has been manifested in rodent studies as high mortality of prenatally exposed newborn rats and mice within 24 h after delivery. The nervous system appears to be one of the most sensitive targets of environmental contaminants. The serious developmental effects of PFCs have lead to the upcoming of studies that have investigated neurotoxic effects of these substances. In this review the major findings of the neurotoxicity of the main PFCs and their suggested mechanisms of action are presented. The neurotoxic effects are discussed in light of other toxic effects of PFCs to indicate the significance of PFCs as neurotoxicants. The main findings are that PFCs may induce neurobehavioral effects, particularly in developmentally exposed animals. The effects are, however, subtle and inconclusive and are often induced at concentrations where other toxic effects also are expected. Mechanistic studies have shown that PFCs may affect the thyroid system, influence the calcium homeostasis, protein kinase C, synaptic plasticity and cellular differentiation. Compared to other environmental toxicants the human blood levels of PFCs are high and of particular concern is that susceptible groups may be exposed to a cocktail of substances that in combination reach harmful concentrations.

  9. Sulfonamide antibiotic removal and nitrogen recovery from synthetic urine by the combination of rotating advanced oxidation contactor and methylene urea synthesis process.

    Science.gov (United States)

    Fukahori, S; Fujiwara, T; Ito, R; Funamizu, N

    2015-01-01

    The combination of nitrogen recovery and pharmaceutical removal processes for livestock urine treatment were investigated to suppress the discharge of pollutants and recover nitrogen as resources. We combined methylene urea synthesis from urea and adsorption and photocatalytic decomposition of sulfonamide antibiotic using rotating advanced oxidation contactor (RAOC) contained for obtaining both safe fertilizer and reclaimed water. The methylene urea synthesis could recover urea in synthetic urine, however, almost all sulfonamide antibiotic was also incorporated, which is unfavorable from a safety aspect if the methylene urea is to be used as fertilizer. Conversely, RAOC could remove sulfonamide antibiotic without consuming urea. It was also confirmed that the methylene urea could be synthesized from synthetic urine treated by RAOC. Thus, we concluded that RAOC should be inserted prior to the nitrogen recovery process for effective treatment of urine and safe use of methylene urea as fertilizer.

  10. Mixed WTO ruling on generic drug development.

    Science.gov (United States)

    Elliott, R

    2000-01-01

    On 17 March 2000, the World Trade Organization upheld the provision in Canada's patent laws that allows generic drug manufacturers to develop (but not sell) their cheaper versions of patented medicines before the 20-year patients expire. The decision prevents pharmaceutical companies from enjoying market monopolies beyond their patent terms, avoiding what would otherwise be even lengthier delays in the sale of cheaper, generic drugs in Canada. This decision is of significance not only to Canada, but also to other WTO member countries and to all individuals who use pharmaceutical products. However, the decision is not all positive: the WTO also ruled that Canada is violating international agreements by letting generic manufacturers stockpile their versions of patented drugs before patents expire. This article explains the issues, the arguments, and the decision.

  11. Benefits of Digital Equipment Generic Qualification Activities

    International Nuclear Information System (INIS)

    Thomas, James E.; Steiman, Samuel C.

    2002-01-01

    As a result of nuclear power plant instrumentation and control obsolescence issues, there have been numerous activities during recent years relating to the qualification of digital equipment. Some of these activities have been 'generic' in nature in that the qualification was not limited to plant specific applications, but was intended to cover a broad base of potential applications of the digital equipment. These generic qualifications have been funded by equipment manufacturers and by utility groups and organizations. The generic activities sponsored by the Electric Power Research Institute (EPRI) have been pilot projects for an overall generic qualification approach. The primary benefit resulting from the generic qualification work to date is that a number of digital platforms and digital devices are now available for use in various nuclear safety-related applications. Many of the tests and evaluations necessary to support plant specific applications have been completed. The amount of data and documentation that each utility must develop on a case by case basis has been significantly reduced. There are also a number of additional benefits resulting from these industry efforts. The challenges and difficulties in qualifying digital equipment for safety-related applications are now more clearly understood. EPRI has published a lessons learned document (EPRI Report 1001452, Generic Qualification of Commercial Grade Digital Devices: Lessons Learned from Initial Pilots, which covers several different qualification areas, including device selection, project planning, vendor surveys and design reviews, and electromagnetic compatibility (EMC) qualification. Application of the experience and lessons learned from the EPRI pilot activities should help reduce the effort and cost required for future qualification work. Most generic qualification activities for commercial equipment have been conducted using the approach of EPRI TR-106439, Guideline on Evaluation and Acceptance

  12. Generic tacrolimus in solid organ transplantation

    DEFF Research Database (Denmark)

    Taube, D; Jones, G; O'Beirne, J

    2014-01-01

    The availability of a wide range of immunosuppressive therapies has revolutionized the management of patients who have undergone solid organ transplantation (SOT). However, the cost of immunosuppressive drugs remains high. This situation has led to the development of generic equivalents, which...... innovator tacrolimus drug (Prograf) in both healthy volunteers and kidney transplant patients. Clinical experience with this generic tacrolimus formulation has also been established in both de novo and conversion patients who have undergone kidney and liver transplantation, as well as in conversion of other...

  13. The SENSEI Generic In Situ Interface

    Energy Technology Data Exchange (ETDEWEB)

    Ayachit, Utkarsh [Kitware, Inc., Clifton Park, NY (United States); Whitlock, Brad [Intelligent Light, Rutherford, NJ (United States); Wolf, Matthew [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Loring, Burlen [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Geveci, Berk [Kitware, Inc., Clifton Park, NY (United States); Lonie, David [Kitware, Inc., Clifton Park, NY (United States); Bethel, E. Wes [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2017-04-11

    The SENSEI generic in situ interface is an API that promotes code portability and reusability. From the simulation view, a developer can instrument their code with the SENSEI API and then make make use of any number of in situ infrastructures. From the method view, a developer can write an in situ method using the SENSEI API, then expect it to run in any number of in situ infrastructures, or be invoked directly from a simulation code, with little or no modification. This paper presents the design principles underlying the SENSEI generic interface, along with some simplified coding examples.

  14. Generic magnetic fusion reactor cost assessment

    International Nuclear Information System (INIS)

    Sheffield, J.

    1985-01-01

    The Fusion Energy Division of the Oak Ridge National Laboratory discusses ''generic'' magnetic fusion reactors. The author comments on DT burning magnetic fusion reactor models being possibly operational in the 21st century. Representative parameters from D-T reactor studies are given, as well as a shematic diagram of a generic fusion reactor. Values are given for winding pack current density for existing and future superconducting coils. Topics included are the variation of the cost of electricity (COE), the dependence of the COE on the net electric power of the reactor, and COE formula definitions

  15. Continuous degradation of a mixture of sulfonamides by Trametes versicolor and identification of metabolites from sulfapyridine and sulfathiazole

    International Nuclear Information System (INIS)

    Rodríguez-Rodríguez, Carlos E.; Jesús García-Galán, Ma.; Blánquez, Paqui; Díaz-Cruz, M. Silvia; Barceló, Damià; Caminal, Glòria; Vicent, Teresa

    2012-01-01

    Highlights: ► Degradation of sulfapyridine and sulfathiazole by Trametes versicolor was evaluated. ► The role of laccase and cytochrome P450 was determined. ► Degradation metabolites were identified for sulfapyridine (8) and sulfathiazole (5). ► A mixture of three sulfonamides was degraded in a continuous fluidized bed reactor. - Abstract: In this study, we assessed the degradation of the sulfonamides sulfapyridine (SPY) and sulfathiazole (STZ) by the white-rot fungus Trametes versicolor. Complete degradation was accomplished in fungal cultures at initial pollutant concentrations of approximately 10 mg L −1 , although a longer period of time was needed to completely remove STZ in comparison to SPY. When cytochrome P450 inhibitors were added to the fungal cultures, STZ degradation was partially suppressed, while no additional effect was observed for SPY. Experiments with purified laccase and laccase mediators caused the removal of greater than 75% of each antibiotic. Ultra-performance liquid chromatography-quadupole time of flight mass spectrometry (UPLC-QqTOF-MS) analyses allowed the identification of a total of eight degradation intermediates of SPY in both the in vivo and the laccase experiments, being its desulfonated moiety the commonly detected product. For STZ, a total of five products were identified. A fluidized bed reactor with T. versicolor pellets degraded a mixture of sulfonamides (SPY, STZ and sulfamethazine, SMZ) by greater than 94% each at a hydraulic residence time of 72 h. Because wastewater contains many diverse pollutants, these results highlight the potential of T. versicolor as a bioremediation agent not only for the removal of antibiotics but also for the elimination of a wide range of contaminants.

  16. Continuous degradation of a mixture of sulfonamides by Trametes versicolor and identification of metabolites from sulfapyridine and sulfathiazole

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Rodriguez, Carlos E., E-mail: CarlosEsteban.Rodriguez@uab.cat [Unitat asociada de Biocatalisi Aplicada IQAC-CSIC, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Centro de Investigacion en Contaminacion Ambiental, Universidad de Costa Rica, 2060 San Jose (Costa Rica); Jesus Garcia-Galan, Ma. [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Blanquez, Paqui [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Diaz-Cruz, M. Silvia [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Barcelo, Damia [Departament de Quimica Ambiental, IDAEA-CSIC, C/Jordi Girona 18-26, 08034, Barcelona (Spain); Catalan Institute for Water Research (ICRA), Parc Cientific i Tecnologic de la Universitat de Girona, C/Emili Grahit, 101 Edifici H2O, E-17003 Girona (Spain); Caminal, Gloria [Unitat asociada de Biocatalisi Aplicada IQAC-CSIC, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain); Vicent, Teresa [Departament d' Enginyeria Quimica, Escola d' Enginyeria, Universitat Autonoma de Barcelona, 08193 Bellaterra, Barcelona (Spain)

    2012-04-30

    Highlights: Black-Right-Pointing-Pointer Degradation of sulfapyridine and sulfathiazole by Trametes versicolor was evaluated. Black-Right-Pointing-Pointer The role of laccase and cytochrome P450 was determined. Black-Right-Pointing-Pointer Degradation metabolites were identified for sulfapyridine (8) and sulfathiazole (5). Black-Right-Pointing-Pointer A mixture of three sulfonamides was degraded in a continuous fluidized bed reactor. - Abstract: In this study, we assessed the degradation of the sulfonamides sulfapyridine (SPY) and sulfathiazole (STZ) by the white-rot fungus Trametes versicolor. Complete degradation was accomplished in fungal cultures at initial pollutant concentrations of approximately 10 mg L{sup -1}, although a longer period of time was needed to completely remove STZ in comparison to SPY. When cytochrome P450 inhibitors were added to the fungal cultures, STZ degradation was partially suppressed, while no additional effect was observed for SPY. Experiments with purified laccase and laccase mediators caused the removal of greater than 75% of each antibiotic. Ultra-performance liquid chromatography-quadupole time of flight mass spectrometry (UPLC-QqTOF-MS) analyses allowed the identification of a total of eight degradation intermediates of SPY in both the in vivo and the laccase experiments, being its desulfonated moiety the commonly detected product. For STZ, a total of five products were identified. A fluidized bed reactor with T. versicolor pellets degraded a mixture of sulfonamides (SPY, STZ and sulfamethazine, SMZ) by greater than 94% each at a hydraulic residence time of 72 h. Because wastewater contains many diverse pollutants, these results highlight the potential of T. versicolor as a bioremediation agent not only for the removal of antibiotics but also for the elimination of a wide range of contaminants.

  17. Sulfonamide-resistant bacteria and their resistance genes in soils fertilized with manures from Jiangsu Province, Southeastern China.

    Directory of Open Access Journals (Sweden)

    Na Wang

    Full Text Available Antibiotic-resistant bacteria and genes are recognized as new environmental pollutants that warrant special concern. There were few reports on veterinary antibiotic-resistant bacteria and genes in China. This work systematically analyzed the prevalence and distribution of sulfonamide resistance genes in soils from the environments around poultry and livestock farms in Jiangsu Province, Southeastern China. The results showed that the animal manure application made the spread and abundance of antibiotic resistance genes (ARGs increasingly in the soil. The frequency of sulfonamide resistance genes was sul1 > sul2 > sul3 in pig-manured soil DNA and sul2 > sul1 > sul3 in chicken-manured soil DNA. Further analysis suggested that the frequency distribution of the sul genes in the genomic DNA and plasmids of the SR isolates from manured soil was sul2 > sul1 > sul3 overall (p<0.05. The combination of sul1 and sul2 was the most frequent, and the co-existence of sul1 and sul3 was not found either in the genomic DNA or plasmids. The sample type, animal type and sampling time can influence the prevalence and distribution pattern of sulfonamide resistance genes. The present study also indicated that Bacillus, Pseudomonas and Shigella were the most prevalent sul-positive genera in the soil, suggesting a potential human health risk. The above results could be important in the evaluation of antibiotic-resistant bacteria and genes from manure as sources of agricultural soil pollution; the results also demonstrate the necessity and urgency of the regulation and supervision of veterinary antibiotics in China.

  18. Synthesis of some new heterocyclic compounds bearing a sulfonamide moiety and studying their combined anticancer effect with γ-radiation

    International Nuclear Information System (INIS)

    El-Hossary, E.M.M.

    2010-01-01

    In search for new cytotoxic agents with improved anticancer profile, some new halogen-containing quinoline and pyrimido[4,5-b]quinoline derivatives bearing a free sulfonamide moiety were synthesized. All the newly synthesized target compounds were subjected to in vitro anticancer screening against human breast cancer cell line (MCF7). The most potent compounds, as concluded from the in vitro anticancer screening, were selected to be evaluated again for their in vitro anticancer activity in combination with radiation. Also, the newly synthesized compounds were docked in the active site of the carbonic anhydrase enzyme

  19. Prevalence and characterization of plasmids carrying sulfonamide resistance genes among Escherichia coli from pigs, pig carcasses and human

    DEFF Research Database (Denmark)

    Shuyu, Wu; Dalsgaard, A.; Hammerum, A. M.

    2010-01-01

    isolates. Fifty-seven sulfonamide-resistant E. coli were selected based on presence of sul resistance genes and subjected to conjugation and/or transformation experiments. S1 nuclease digestion followed by pulsed-field gel electrophoresis was used to visualize and determine the size of plasmids. Plasmids...... and humans) were 65%, 45% and 12% for sul2, sul1, and sul3, respectively. Transfer of resistance through conjugation was observed in 42/57 isolates. Resistances to streptomycin, ampicillin and trimethoprim were co-transferred in most strains. Class 1 integrons were present in 80% of sul1-carrying plasmids...

  20. Studying the interaction between three synthesized heterocyclic sulfonamide compounds with hemoglobin by spectroscopy and molecular modeling techniques.

    Science.gov (United States)

    Naeeminejad, Samane; Assaran Darban, Reza; Beigoli, Sima; Saberi, Mohammad Reza; Chamani, Jamshidkhan

    2017-11-01

    The interaction between synthesized heterocyclic benzene sulfonamide compounds, N-(7-benzyl-56-biphenyl-2m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-benzene sulfonamide (HBS 1 ), N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d] pyrimidine-4-yl)-4-methyl- benzene sulfonamide (HBS 2 ), and N-(7-benzyl-56-biphenyl-2-m-tolyl-7H-pyrrolo[23-d]pyrimidine-4-yl)-4-chloro-benzene sulfonamide (HBS 3 ) with Hb was studied by fluorescence quenching, zeta potentional, circular dichroism, and molecular modeling techniques. The fluorescence spectroscopy experiments were performed in order to study the conformational changes, possibly due to a discrete reorganization of Trp residues during binding between HBS derivatives and Hb. The variation of the K SV value suggested that hydrophobic and electrostatic interactions were the predominant intermolecular forces stabilizing the complex. The K SV1 ans K SV2 values of HBS derivatives with Hb are .6 × 10 13 and 3 × 10 13  M -1 for Hb-HBS 1 , 1 × 10 13 and 4 × 10 13  M -1 for Hb-HBS 2 , .9 × 10 13 , and 6 × 10 13  M -1 for Hb-HBS 3 , respectively. The molecular distances between Hb and HBS derivatives in binary and ternary systems were estimated according to Förster's theory of dipole-dipole non-radiation energy transfer. The quantitative analysis data of circular dichroism spectra demonstrated that the binding of the three HBS derivatives to Hb induced conformational changes in Hb. Changes in the zeta potential of the Hb-HBS derivatives complexes demonstrated a hydrophobic adsorption of the anionic ligand onto the surface of Hb as well as both electrostatic and hydrophobic adsorption in the case of the complex. The modeling data thus confirmed the experimental results. This study is expected to provide important insight into the interaction of Hb with three HBS derivatives to use in various toxicological and therapeutic processes.

  1. A new sulfonamide resistance gene (sul3) in Escherichia coli is widespread in the pig population of Switzerland.

    Science.gov (United States)

    Perreten, Vincent; Boerlin, Patrick

    2003-03-01

    A new gene, sul3, which specifies a 263-amino-acid protein similar to a dihydropteroate synthase encoded by the 54-kb conjugative plasmid pVP440 from Escherichia coli was characterized. Expression of the cloned sul3 gene conferred resistance to sulfamethoxazole on E. coli. Two copies of the insertion element IS15Delta/26 flanked the region containing sul3. The sul3 gene was detected in one-third of the sulfonamide-resistant pathogenic E. coli isolates from pigs in Switzerland.

  2. A New Sulfonamide Resistance Gene (sul3) in Escherichia coli Is Widespread in the Pig Population of Switzerland

    OpenAIRE

    Perreten, Vincent; Boerlin, Patrick

    2003-01-01

    A new gene, sul3, which specifies a 263-amino-acid protein similar to a dihydropteroate synthase encoded by the 54-kb conjugative plasmid pVP440 from Escherichia coli was characterized. Expression of the cloned sul3 gene conferred resistance to sulfamethoxazole on E. coli. Two copies of the insertion element IS15Δ/26 flanked the region containing sul3. The sul3 gene was detected in one-third of the sulfonamide-resistant pathogenic E. coli isolates from pigs in Switzerland.

  3. The origin of enantioselectivity in the l-threonine-derived phosphine-sulfonamide catalyzed aza-Morita-Baylis-Hillman reaction: Effects of the intramolecular hydrogen bonding

    KAUST Repository

    Lee, Richmond

    2013-01-01

    l-Threonine-derived phosphine-sulfonamide 4 was identified as the most efficient catalyst to promote enantioselective aza-Morita-Baylis-Hillman (MBH) reactions, affording the desired aza-MBH adducts with excellent enantioselectivities. Density functional theory (DFT) studies were carried out to elucidate the origin of the observed enantioselectivity. The importance of the intramolecular N-H⋯O hydrogen-bonding interaction between the sulfonamide and enolate groups was identified to be crucial in inducing a high degree of stereochemical control in both the enolate addition to imine and the subsequent proton transfer step, affording aza-MBH reactions with excellent enantioselectivity. © 2013 The Royal Society of Chemistry.

  4. Associations between generic substitution and patients' attitudes, beliefs and experience

    DEFF Research Database (Denmark)

    Østergaard Rathe, Jette; Larsen, Pia Veldt; Andersen, Morten

    2013-01-01

    Abstract Background Generic substitution has been implemented in many countries, but knowledge about patients’ attitudes, beliefs and experiences is still sparse. Aim To assess associations between generic switching and patients’ attitudes, beliefs and experiences with previous generic switching...... on generic medicine and confidence in the healthcare system. Only prescriptions issued by the general practitioners were included. For each patient we focused on one purchase of a generically substitutable drug (index drug). Patients were identified by means of a dispensing database. Results Earlier generic...... switches within the index ATC code were statistically significantly associated with experience of a generic switch (adjusted OR 5.93 95% CI 4.70; 7.49). Having had more than 5 earlier switches within other ATC codes and having negative views on generic medicines reduced the odds of experiencing a generic...

  5. Towards Generic Interaction Styles for Product Design

    DEFF Research Database (Denmark)

    Buur, Jacob; Stienstra, Marcelle

    2008-01-01

    a wider range of interactive products. In this paper we report on five years of continued research into interaction styles for telephones, kitchen equipment, HiFi products and medical devices, and we show how it is indeed possible and beneficial to formulate a set of generic interaction styles....

  6. Crystallization Kinetics within a Generic Modelling Framework

    DEFF Research Database (Denmark)

    Meisler, Kresten Troelstrup; von Solms, Nicolas; Gernaey, Krist

    2013-01-01

    An existing generic modelling framework has been expanded with tools for kinetic model analysis. The analysis of kinetics is carried out within the framework where kinetic constitutive models are collected, analysed and utilized for the simulation of crystallization operations. A modelling...... procedure is proposed to gain the information of crystallization operation kinetic model analysis and utilize this for faster evaluation of crystallization operations....

  7. Baldrige Theory into Practice: A Generic Model

    Science.gov (United States)

    Arif, Mohammed

    2007-01-01

    Purpose: The education system globally has moved from a push-based or producer-centric system to a pull-based or customer centric system. Malcolm Baldrige Quality Award (MBQA) model happens to be one of the latest additions to the pull based models. The purpose of this paper is to develop a generic framework for MBQA that can be used by…

  8. Generic Checklist for Day Care Monitoring.

    Science.gov (United States)

    Children's Services Monitoring Transfer Consortium.

    This guide presents the results of research on day care monitoring methods conducted by the Children's Services Monitoring Transfer Consortium. It suggests a set of generic predictor items that can be used to monitor day care providers' compliance with standards. The predictor items are at the licensing or minimal compliance level and have been…

  9. Climate Change: Generic Implications for Agriculture

    Indian Academy of Sciences (India)

    Climate Change: Generic Implications for Agriculture. Increasing carbon dioxide: Good for most crops. Increase in mean temperature: orter ... Increasing rainfall intensity and dry days- more floods and droughts: Higher production variability. Himalayan glaciers to recede: irrigation in IGP gradually becomes less dependable ...

  10. A Generic Solution Approach to Nurse Rostering

    DEFF Research Database (Denmark)

    Hansen, Anders Dohn; Mason, Andrew; Ryan, David

    In this report, we present a solution approach to the nurse rostering problem. The problem is defined by a generic model that is able to capture close to all of the problem characteristics that we have seen in the literature and in the realistic problems at hand. The model is used directly in the...

  11. The Generic Style Rules for Linguistics

    OpenAIRE

    Haspelmath, Martin

    2014-01-01

    The Generic Style Rules for Linguistics provide a style sheet that can be used by any linguistics journal or edited book, or for teaching purposes. They regulate aspects of text-structure style such as typographic highlighting, citation style, use of capitalization, and bibliographic style (based on the LSA's Unified Stylesheet for linguistics).

  12. Generic hyper-diversity in Stachybotriaceae

    Czech Academy of Sciences Publication Activity Database

    Lombard, L.; Houbraken, J.; Decock, C.; Samson, R.A.; Meijer, M.; Réblová, Martina; Groenewald, J.Z.; Crous, P. W.

    2016-01-01

    Roč. 36, SI Jun (2016), s. 156-246 ISSN 0031-5850 R&D Projects: GA ČR GAP506/12/0038 Institutional support: RVO:67985939 Keywords : biodegraders * generic concept * human and plant pathogens Subject RIV: EF - Botanics Impact factor: 7.511, year: 2016

  13. Generic Principles for Resolving Intergroup Conflict.

    Science.gov (United States)

    Fisher, Ronald J.

    1994-01-01

    Provides an initial statement of generic principles deemed effective for addressing protracted social conflicts between identity groups. These principles are compatible with certain values for societal organization and approaches to social change, raising questions of value differences between intervenors and the host culture(s). Three case…

  14. Intermediates and Generic Convergence to Equilibria

    DEFF Research Database (Denmark)

    Marcondes de Freitas, Michael; Wiuf, Carsten; Feliu, Elisenda

    2017-01-01

    Known graphical conditions for the generic and global convergence to equilibria of the dynamical system arising from a reaction network are shown to be invariant under the so-called successive removal of intermediates, a systematic procedure to simplify the network, making the graphical conditions...

  15. Generic Certificates. Agricultural Economic Report Number 594.

    Science.gov (United States)

    Glauber, Joseph W.

    The Food Security Act of 1985 authorizes the U.S. Department of Agriculture to issue generic certificates in lieu of cash payments due to program participants and merchants of agricultural products under provisions of several programs. The certificates may be used to acquire stocks held as collateral on government loans or owned by the Commodity…

  16. Poly- and perfluoroalkyl substances (PFASs) in raw and drinking water - current situation in Sweden, Denmark and Germany

    Science.gov (United States)

    Banzhaf, Stefan; Bester, Kai; Filipovic, Marko; Lewis, Jeffrey; Licha, Tobias; Sparrenbom, Charlotte; Barthel, Roland

    2016-04-01

    Poly- and perfluoroalkyl substances (PFASs) are a group of anthropogenic environmental pollutants which have been used and produced for more than 60 years. PFASs are used for multiple industrial purposes, e.g. as water repellent on clothing, leather, and paper and as firefighting foam. The most well studied PFASs subgroup are perfluoroalkyl acids (PFAA). Two PFAAs of particular interest are perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA). These are the most studied homologues which are ubiquitously detected in the aquatic environment, wildlife and humans. Some PFASs are recognized as being potentially toxic for both animals and humans (e.g. PFOS), whereas the majority has not been thoroughly studied yet regarding their toxicity. PFAAs are highly mobile once present in the aquatic environment. Currently, they are not eliminated during conventional wastewater or drinking water treatment and therefore pose a severe threat for drinking water supply. We reviewed the current occurrence of PFAAs in the surface and groundwater and legal situation of PFAAs in Sweden, Denmark and Germany. Although first detections of PFAAs were reported in the early 2000s, PFASs only recently attracted huge media attention raising public concern. In Sweden, for instance, several public waterworks needed to cease operation due to high PFASs concentrations in drinking water. Moreover, threshold values for drinking water are under discussion and a first preliminary guiding value for PFOS was recently presented as a first step (Pettersson et al., 2015). Germany only defined a guiding value for the sum of PFOS and PFOA in drinking water so far (Dieter, 2011). Limits of 0.3 μg/L PFOA and 0.1 μg/L PFOS and PFOSA each have been suggested in Denmark (MST, 2015). In summary, none of the three countries has defined a clear threshold value for any PFAS compound in drinking water so far. This is of huge concern as PFASs are detected at increasing rates while it remains unclear when

  17. Sulfonamide inhibition studies of the β-carbonic anhydrase from the newly discovered bacterium Enterobacter sp. B13.

    Science.gov (United States)

    Eminoğlu, Ayşenur; Vullo, Daniela; Aşık, Aycan; Çolak, Dilşat Nigar; Çanakçı, Sabriye; Beldüz, Ali Osman; Supuran, Claudiu T

    2016-04-01

    The genome of the newly identified bacterium Enterobacter sp. B13 encodes for a β-class carbonic anhydrases (CAs, EC 4.2.1.1), EspCA. This enzyme was recently cloned, and characterized kinetically by this group (J. Enzyme Inhib. Med. Chem. 2016, 31). Here we report an inhibition study with sulfonamides and sulfamates of this enzyme. The best EspCA inhibitors were some sulfanylated sulfonamides with elongated molecules, metanilamide, 4-aminoalkyl-benzenesulfonamides, acetazolamide, and deacetylated methazolamide (KIs in the range of 58.7-96.5nM). Clinically used agents such as methazolamide, ethoxzolamide, dorzolamide, brinzolamide, benzolamide, zonisamide, sulthiame, sulpiride, topiramate and valdecoxib were slightly less effective inhibitors (KIs in the range of 103-138nM). Saccharin, celecoxib, dichlorophenamide and many simple benzenesulfonamides were even less effective as EspCA inhibitors, with KIs in the range of 384-938nM. Identification of effective inhibitors of this bacterial enzyme may lead to pharmacological tools useful for understanding the physiological role(s) of the β-class CAs in bacterial pathogenicity/virulence. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Antibacterial activity of sulfamethoxazole transformation products (TPs): general relevance for sulfonamide TPs modified at the para position.

    Science.gov (United States)

    Majewsky, Marius; Wagner, Danny; Delay, Markus; Bräse, Stefan; Yargeau, Viviane; Horn, Harald

    2014-10-20

    Sulfonamide antibiotics undergo transformation in the aquatic environment through biodegradation, photolysis, or hydrolysis. In this study, the residual antibacterial activity of 11 transformation products (TPs) of sulfamethoxazole (SMX) was investigated with regard to their in vitro growth and luminescence inhibition on Vibrio fischeri (30 min and 24 h exposure). Two transformation products, 4-hydroxy-SMX and N(4)-hydroxy-acetyl-SMX, were synthesized in-house and confirmed by nuclear magnetic resonance and high-resolution mass spectrometry. Results of individual compound experiments showed that TPs modified at the para amino group still exhibit clear antibacterial effects, whereas TPs resulting from breakdown of the SMX structure lost this mechanism of action. 4-NO2- and 4-OH-SMX were found to inhibit growth to a clearly greater extent than the parent compound, SMX. In contrast, the N(4)-acetyl- and N(4)-hydroxy-acetyl-derivatives retain less than 10 and 5% of the effect of SMX on growth and luminescence inhibition, respectively. The effect of a mixture of para-modified TPs was observed to be additive. Considering the homologous series of sulfa drugs widely prescribed and their common mechanism of action, the potential environmental impact must consider the total amount of sulfonamide antibiotics and their derivative TPs, which might end up in a water body. Extrapolating the results obtained here for the para TPs of SMX to other sulfa drugs and determining the persistence and occurrence of these compounds in the aquatic environment is required for improved risk assessment.

  19. Spiramycin/cotrimoxazole versus pyrimethamine/sulfonamide and spiramycin alone for the treatment of toxoplasmosis in pregnancy.

    Science.gov (United States)

    Valentini, P; Buonsenso, D; Barone, G; Serranti, D; Calzedda, R; Ceccarelli, M; Speziale, D; Ricci, R; Masini, L

    2015-02-01

    To compare the effectiviness of spiramycin/cotrimoxazole (Sp/C) versus pyrimethamine/sulfonamide (Pyr/Sul) and spiramycin alone (Spy) on mother-to-child transmission of toxoplasmosis infection in pregnancy. Retrospective study of pregnant women evaluated for suspected toxoplasmosis between 1992 and 2011. A total of 120 mothers and their 123 newborns were included. Prenatal treatment consisted of spiramycin in 43 mothers (35%), spiramycin/cotrimoxazole in 70 (56.9%) and pyrimethamine/sulfonamide in 10 (8.1%). A trend toward reduction in toxoplasmosis transmission was found when Sp/C was compared with Pyr/Sul and particularly with Spy alone (P=0.014). In particular, Spy increased the risk of congenital infection when compared with Sp/C (odds ratio (OR) 4.368; 95% CI: 1.253 to 15.219), but there was no significant reduction when Sp/C was compared with Pyr/Sul (OR 1.83; 95% CI: 0.184 to 18.274). The treatment based on Sp/C has significant efficacy in reducing maternal-fetal transmission of Toxoplasma gondii when compared with Pyr/Sul and particularly to Spy. Randomized controlled trials would be required.

  20. Excellent performance of copper based metal organic framework in adsorptive removal of toxic sulfonamide antibiotics from wastewater.

    Science.gov (United States)

    Azhar, Muhammad Rizwan; Abid, Hussein Rasool; Sun, Hongqi; Periasamy, Vijay; Tadé, Moses O; Wang, Shaobin

    2016-09-15

    The increasing concerns on toxicity of sulfonamide antibiotics in water require a prompt action to establish efficient wastewater treatment processes for their removal. In this study, adsorptive removal of a model sulfonamide antibiotic, sulfachloropyridazine (SCP), from wastewater is presented for the first time using a metal organic framework (MOF). A high surface area and thermally stable MOF, HKUST-1, was synthesized by a facile method. Batch adsorption studies were systematically carried out using HKUST-1. The high surface area and unsaturated metal sites resulted in a significant adsorption capacity with faster kinetics. Most of the SCP was removed in 15min and the kinetic data were best fitted with the pseudo second order model. Moreover, isothermal data were best fitted with the Langmuir model. The thermodynamic results showed that the adsorption is a spontaneous and endothermic process. The adsorption capacity of HKUST-1 is 384mg/g at 298K which is the highest compared to most of the materials for the antibiotics. The high adsorption capacity is attributed mainly to π-π stacking, hydrogen bonding and electrostatic interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Chlorination and oxidation of sulfonamides by free chlorine: Identification and behaviour of reaction products by UPLC-MS/MS.

    Science.gov (United States)

    Gaffney, Vanessa de Jesus; Cardoso, Vitor Vale; Benoliel, Maria João; Almeida, Cristina M M

    2016-01-15

    Sulfonamides (SAs) are one class of the most widely used antibiotics around the world and have been frequently detected in municipal wastewater and surface water in recent years. Their transformation in waste water treatment plants (WWTP) and in water treatment plants (WTP), as well as, their fate and transport in the aquatic environment are of concern. The reaction of six sulfonamides (sulfamethoxazole, sulfapyridine, sulfamethazine, sulfamerazine, sulfathiazole and sulfadiazine) with free chlorine was investigated at a laboratory scale in order to identify the main chlorination by-products. A previously validated method, liquid chromatography/mass spectrometry, was used to analyse SAs and their chlorination by-products. At room temperature, pH 6-7, reaction times of up to 2 h and an initial concentration of 2 mg/L of free chlorine, the majority of SAs suffered degradation of around 65%, with the exception of sulfamethoxazole and sulfathiazole (20%). The main reaction of SAs with free chlorine occurred in the first minute. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Room Temperature Synthesis and Antibacterial Activity of New Sulfonamides Containing N,N-Diethyl-Substituted Amido Moieties

    Directory of Open Access Journals (Sweden)

    Olayinka O. Ajani

    2012-01-01

    Full Text Available Sulfonamide drugs which have brought about an antibiotic revolution in medicine are associated with a wide range of biological activities. We have synthesized a series of α-tolylsulfonamide, 1–11 and their substituted N,N-diethyl-2-(phenylmethylsulfonamido alkanamide derivatives, 12–22 in improved and excellent yields in aqueous medium at room temperature through highly economical synthetic routes. The chemical structures of the synthesized compounds 1–22 were confirmed by analytical and spectral data such as IR, 1H- and 13C-NMR, and mass spectra. The in vitro antibacterial activity of these compounds along with standard clinical reference, streptomycin, was investigated on two key targeted organisms. It was observed that 1-(benzylsulfonylpyrrolidine-2-carboxylic acid, 2 emerged as the most active compound against Staphylococcus aureus at MIC value of 1.8 μg/mL while 4-(3-(diethylamino-3-oxo-2-(phenylmethylsulfonamido propylphenyl phenylmethanesulfonate, 22 was the most active sulfonamide scaffold on Escherichia coli at MIC value of 12.5 μg/mL.

  3. Development and validation of an LC-UV method for the determination of sulfonamides in animal feeds.

    Science.gov (United States)

    Kumar, P; Companyó, R

    2012-05-01

    A simple LC-UV method was developed for the determination of residues of eight sulfonamides (sulfachloropyridazine, sulfadiazine, sulfadimidine, sulfadoxine, sulfamethoxypyridazine, sulfaquinoxaline, sulfamethoxazole, and sulfadimethoxine) in six types of animal feed. C18, Oasis HLB, Plexa and Plexa PCX stationary phases were assessed for the clean-up step and the latter was chosen as it showed greater efficiency in the clean-up of interferences. Feed samples spiked with sulfonamides at 2 mg/kg were used to assess the trueness (recovery %) and precision of the method. Mean recovery values ranged from 47% to 66%, intra-day precision (RSD %) from 4% to 15% and inter-day precision (RSD %) from 7% to 18% in pig feed. Recoveries and intra-day precisions were also evaluated in rabbit, hen, cow, chicken and piglet feed matrices. Calibration curves with standards prepared in mobile phase and matrix-matched calibration curves were compared and the matrix effects were ascertained. The limits of detection and quantification in the feeds ranged from 74 to 265 µg/kg and from 265 to 868 µg/kg, respectively. Copyright © 2011 John Wiley & Sons, Ltd.

  4. Sulfonamide-resistant bacteria and their resistance genes in soils fertilized with manures from Jiangsu Province, Southeastern China.

    Science.gov (United States)

    Wang, Na; Yang, Xiaohong; Jiao, Shaojun; Zhang, Jun; Ye, Boping; Gao, Shixiang

    2014-01-01

    Antibiotic-resistant bacteria and genes are recognized as new environmental pollutants that warrant special concern. There were few reports on veterinary antibiotic-resistant bacteria and genes in China. This work systematically analyzed the prevalence and distribution of sulfonamide resistance genes in soils from the environments around poultry and livestock farms in Jiangsu Province, Southeastern China. The results showed that the animal manure application made the spread and abundance of antibiotic resistance genes (ARGs) increasingly in the soil. The frequency of sulfonamide resistance genes was sul1 > sul2 > sul3 in pig-manured soil DNA and sul2 > sul1 > sul3 in chicken-manured soil DNA. Further analysis suggested that the frequency distribution of the sul genes in the genomic DNA and plasmids of the SR isolates from manured soil was sul2 > sul1 > sul3 overall (psulfonamide resistance genes. The present study also indicated that Bacillus, Pseudomonas and Shigella were the most prevalent sul-positive genera in the soil, suggesting a potential human health risk. The above results could be important in the evaluation of antibiotic-resistant bacteria and genes from manure as sources of agricultural soil pollution; the results also demonstrate the necessity and urgency of the regulation and supervision of veterinary antibiotics in China.

  5. Prenatal and childhood perfluoroalkyl substances exposures and children's reading skills at ages 5 and 8years.

    Science.gov (United States)

    Zhang, Hongmei; Yolton, Kimberly; Webster, Glenys M; Ye, Xiaoyun; Calafat, Antonia M; Dietrich, Kim N; Xu, Yingying; Xie, Changchun; Braun, Joseph M; Lanphear, Bruce P; Chen, Aimin

    2018-02-01

    Exposure to perfluoroalkyl substances (PFASs) may impact children's neurodevelopment. To examine the association of prenatal and early childhood serum PFAS concentrations with children's reading skills at ages 5 and 8years. We used data from 167 mother-child pairs recruited during pregnancy (2003-2006) in Cincinnati, OH, quantified prenatal serum PFAS concentrations at 16±3weeks of gestation and childhood sera at ages 3 and 8years. We assessed children's reading skills using Woodcock-Johnson Tests of Achievement III at age 5years and Wide Range Achievement Test-4 at age 8years. We used general linear regression to quantify the covariate-adjusted associations between natural log-transformed PFAS concentrations and reading skills, and used multiple informant model to identify the potential windows of susceptibility. Median serum PFASs concentrations were PFOS>PFOA>PFHxS>PFNA in prenatal, 3-year, and 8-year children. The covariate-adjusted general linear regression identified positive associations between serum PFOA, PFOS and PFNA concentrations and children's reading scores at ages 5 and 8years, but no association between any PFHxS concentration and reading skills. The multiple informant model showed: a) Prenatal PFOA was positively associated with higher children's scores in Reading Composite (β: 4.0, 95% CI: 0.6, 7.4 per a natural log unit increase in exposure) and Sentence Comprehension (β: 4.2, 95% CI: 0.5, 8.0) at age 8years; b) 3-year PFOA was positively associated with higher children's scores in Brief Reading (β: 7.3, 95% CI: 0.9, 13.8), Letter Word Identification (β: 6.6, 95% CI: 1.1, 12.0), and Passage Comprehension (β: 5.9, 95% CI: 1.5, 10.2) at age 5years; c) 8-year PFOA was positively associated with higher children's Word Reading scores (β: 5.8, 95% CI: 0.8, 10.7) at age 8years. Prenatal PFOS and PFNA were positively associated with children's reading abilities at age 5years, but not at age 8years; 3-year PFOS and PFNA were positively associated

  6. Perfluoroalkyl acids-induced liver steatosis: Effects on genes controlling lipid homeostasis

    International Nuclear Information System (INIS)

    Das, Kaberi P.; Wood, Carmen R.; Lin, Mimi T.; Starkov, Anatoly A.; Lau, Christopher; Wallace, Kendall B.; Corton, J. Christopher; Abbott, Barbara D.

    2017-01-01

    Highlights: • Structurally diverse PFAAs induced fatty liver and increased TG accumulation in mouse. • Genes of lipid synthesis and degradation were increased after exposure to PFAAs. • PFAAs did not inhibit either mitochondrial fatty acid transport or β-oxidation directly. - Abstract: Persistent presence of perfluoroalkyl acids (PFAAs) in the environment is due to their extensive use in industrial and consumer products, and their slow decay. Biochemical tests in rodent demonstrated that these chemicals are potent modifiers of lipid metabolism and cause hepatocellular steatosis. However, the molecular mechanism of PFAAs interference with lipid metabolism remains to be elucidated. Currently, two major hypotheses are that PFAAs interfere with mitochondrial beta-oxidation of fatty acids and/or they affect the transcriptional activity of peroxisome proliferator-activated receptor α (PPARα) in liver. To determine the ability of structurally-diverse PFAAs to cause steatosis, as well as to understand the underlying molecular mechanisms, wild-type (WT) and PPARα-null mice were treated with perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), or perfluorohexane sulfonate (PFHxS), by oral gavage for 7 days, and their effects were compared to that of PPARα agonist WY-14643 (WY), which does not cause steatosis. Increases in liver weight and cell size, and decreases in DNA content per mg of liver, were observed for all compounds in WT mice, and were also seen in PPARα-null mice for PFOA, PFNA, and PFHxS, but not for WY. In Oil Red O stained sections, WT liver showed increased lipid accumulation in all treatment groups, whereas in PPARα-null livers, accumulation was observed after PFNA and PFHxS treatment, adding to the burden of steatosis observed in control (untreated) PPARα-null mice. Liver triglyceride (TG) levels were elevated in WT mice by all PFAAs and in PPARα-null mice only by PFNA. In vitro β-oxidation of palmitoyl carnitine by isolated rat

  7. Evaluation of perfluoroalkyl acid activity using primary mouse and human hepatocytes

    International Nuclear Information System (INIS)

    Rosen, Mitchell B.; Das, Kaberi P.; Wood, Carmen R.; Wolf, Cynthia J.; Abbott, Barbara D.; Lau, Christopher

    2013-01-01

    While perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been studied at length, less is known about the biological activity of other perfluoroalkyl acids (PFAAs) detected in the environment. Using a transient transfection assay developed in COS-1 cells, our group has previously evaluated a variety of PFAAs for activity associated with activation of peroxisome proliferator-activated receptor alpha (PPARα). Here we use primary heptatocytes to further assess the biological activity of a similar group of PFAAs using custom designed Taqman Low Density Arrays. Primary mouse and human hepatoyctes were cultured for 48 h in the presence of varying concentrations of 12 different PFAAs or Wy14,643, a known activator of PPARα. Total RNA was collected and the expression of 48 mouse or human genes evaluated. Gene selection was based on either in-house liver microarray data (mouse) or published data using primary hepatocytes (human). Gene expression in primary mouse hepatocytes was more restricted than expected. Genes typically regulated in whole tissue by PPARα agonists were not altered in mouse cells including Acox1, Me1, Acaa1a, Hmgcs1, and Slc27a1. Cyp2b10, a gene regulated by the constitutive androstane receptor and a transcript normally up-regulated by in vivo exposure to PFAAs, was also unchanged in cultured mouse hepatocytes. Cyp4a14, Ehhadh, Pdk4, Cpt1b, and Fabp1 were regulated as expected in mouse cells. A larger group of genes were differentially expressed in human primary hepatocytes, however, little consistency was observed across compounds with respect to which genes produced a significant dose response making the determination of relative biological activity difficult. This likely reflects weaker activation of PPARα in human versus rodent cells as well as variation among individual cell donors. Unlike mouse cells, CYP2B6 was up-regulated in human hepatocytes by a number of PFAAs as was PPARδ. Rankings were conducted on the limited

  8. Persistence of perfluoroalkylated substances in closed bottle tests with municipal sewage sludge.

    Science.gov (United States)

    Sáez, Monica; de Voogt, Pim; Parsons, John R

    2008-09-01

    Perfluoroalkylated substances (PFAS) are chemicals with completely fluorinated alkyl chains. The specific properties of the F-C bond give PFAS a high stability and make them very useful in a wide range of applications. PFAS also pose a potential risk to the environment and humans because they have been recently characterized as persistent, bioaccumulative, and toxic. The objective of this work is to study the bacterial degradation of PFAS under aerobic and anaerobic conditions in municipal sewage sludge as a contribution toward understanding their environmental fate and behavior. Bacterial communities from sewage sludge were exposed to a mixture of PFAS under aerobic or anaerobic conditions. Individual PFAS concentrations were determined in the experiment media at different exposure times using liquid chromatography-mass spectrometry analysis after extraction with solid-phase extraction. The PFAS analyses of samples of sludge showed repeatable replicate results, allowing a reliable quantification of the different groups of PFAS analyzed. No conclusive evidence for PFAS degradation was observed under the experimental conditions tested in this work. Reduction in concentrations, however, was observed for some PFAS in sludge under aerobic conditions. The largest concentration decrease occurred for the fluorotelomer alcohols (FTOHs), especially for the 8:2 FTOH, which have been described as biodegradable in the literature. However, this concentration decrease could be due to different causes: sorption to glass, septa, or matrix components, as well as bacterial activity. Therefore, it is not certain that biodegradation occurred. PFAS are very recalcitrant chemicals, especially when fully fluorinated. Although some decreases in concentration have been observed for some PFAS, such as the FTOHs, there is no conclusive evidence for biodegradation. It can be concluded that the PFAS tested in these experiments are non-biodegradable under these experimental conditions. Since

  9. Reliability of perfluoroalkyl substances in plasma of 100 women in two consecutive pregnancies

    Science.gov (United States)

    Papadopoulou, Eleni; Haug, Line S.; Sabaredzovic, Azemira; Eggesbø, Merete; Longnecker, Matthew P.

    2015-01-01

    The potential toxicity of background exposure to perfluoroalkyl substances (PFASs) is currently under active investigation. Such investigations typically rely on a single measure of PFAS concentration, yet the longer-term reliability of a single measure has not been well characterized, especially among reproductive-aged women. Our aim was to investigate the association between PFAS plasma concentrations of 100 women in two consecutive pregnancies and explore changes in plasma concentration related to reproductive factors. The women in our study were enrolled in the Norwegian Mother and Child Cohort Study (MoBa) from 2003 to 2009. About half of them breastfed exclusively for 6 months and the rest of the participants did not breastfeed between the two consecutive pregnancies (median time between pregnancies: 18 months). Maternal blood was collected at mid-pregnancy and plasma was analyzed for 10 PFASs. Statistical analyses were restricted to 6 PFASs that were quantifiable in more than 80% of the samples. We estimated the correlation between repeated PFAS measurements, the percentage change between pregnancies and the effect of several reproductive factors in multivariate linear regression models of PFAS concentration in the second pregnancy. The Pearson correlation coefficient between repeated PFAS measurements was, for perfluorooctane sulfonate (PFOS), 0.80; perfluorooctanoate (PFOA), 0.50; perfluorohexane sulfonate (PFHxS), 0.74; perfluorononanoate (PFNA), 0.39; perfluoroundecanoate (PFUnDA), 0.71; and perfluorodecanoate (PFDA), 0.60. Adjustment for maternal age, delivery year, and time and breastfeeding between pregnancies did not substantially affect the observed correlations. We found 44-47% median reductions in the concentrations of PFOS, PFOA and PFHxS between pregnancies, while the change in concentrations between pregnancies was smaller and more variable for PFNA, PFUnDA and PFDA. The variation in plasma concentrations in the second pregnancy was mainly

  10. Exposure of Norwegian toddlers to perfluoroalkyl substances (PFAS): The association with breastfeeding and maternal PFAS concentrations.

    Science.gov (United States)

    Papadopoulou, Eleni; Sabaredzovic, Azemira; Namork, Ellen; Nygaard, Unni C; Granum, Berit; Haug, Line S

    2016-09-01

    High exposure to perfluoroalkyl substances (PFASs) has been associated with adverse health effects in children. PFASs exposure pathways of toddlers might differ from those of infants and adults, and the investigations on determinants of PFASs exposure in early childhood are scarce. Our aims were to examine the PFAS blood concentrations in Norwegian toddlers and to assess their relationship with maternal PFAS concentrations in pregnancy and breastfeeding duration. We determined PFAS concentrations in 112 plasma samples of 3-year-old children collected at 2010-2011 and 99 maternal serum samples collected around delivery at 2007-2008. PFAS concentrations in children were regressed on duration of breastfeeding, and the effect modification by maternal prenatal PFAS concentrations was examined in 55 mother-child pairs. Six PFASs were quantifiable in >50% of both maternal and children samples. Positive and significant correlations ranging between 0.50 and 0.66 were found between maternal and child concentrations of the same PFAS congeners. Nevertheless, toddlers had higher total PFAS blood concentrations than their mothers, due to higher concentrations of PFOA, PFNA and PFHxS. Every month of breastfeeding was associated with an increase of 3.3% (95% Confidence Intervals (CI): 0.8-5.8) for PFOS, 4.7% (95%CI: 2.8-6.6) for PFOA and 6.1% (95% CI: 2.6-9.7) for PFHpS in toddlers' plasma and a dose-response association was found, after adjustment for confounders. However, PFNA and PFUnDA concentrations in children were not associated with either maternal concentrations or breastfeeding duration. Our findings suggest that transplacental transfer, prenatally, and breastfeeding, postanatally, are among the main determinants of PFOS, PFOA, PFHxS and PFHpS concentrations in toddlers, while that was not the case for PFNA and PFUnDA. Nevertheless, due to the small number of mother child-pairs in our study, our results should be interpreted with caution. Copyright © 2016 Elsevier Ltd

  11. Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances affects leukocyte telomere length in female newborns.

    Science.gov (United States)

    Liu, Han; Chen, Qian; Lei, Lei; Zhou, Wei; Huang, Lisu; Zhang, Jun; Chen, Dan

    2018-04-01

    Evidence has shown that leukocyte telomere length (LTL) at birth is related to the susceptibility to various diseases in later life and the setting of newborn LTL is influenced by the intrauterine environment. Perfluoroalkyl and polyfluoroalkyl substances (PFASs), as a kind of persistent organic pollutants, are commonly used in commercial and domestic applications and are capable of crossing the maternal-fetal barrier during pregnancy. We hypothesized that intrauterine exposure to PFASs may affect fetal LTL by increasing oxidative stress. To verify this hypothesis, LTL, concentrations of PFASs and reactive oxygen species (ROS) were measured in umbilical cord blood of 581 newborns from a prospective cohort. Our results showed that there were interactions between PFOS/PFDA and sex on LTL and ROS. The LTL was significantly shorter (0.926 ± 0.053 vs 0.945 ± 0.054, P = .023 for PFOS; 0.919 ± 0.063 vs 0.940 ± 0.059, P = .011 for PFDA) and the ROS levels were extremely higher (252.9 ± 60.5 [M] vs 233.5 ± 53.6 [M], P = .031 for PFOS; 255.2 ± 62.9 [M] vs 232.9 ± 58.3 [M], P = .011 for PFDA) in the female newborns whose PFOS or PFDA concentrations fell in the upmost quartile compared with those in the lowest quartile after adjusting for potential confounders. ROS levels were inversely associated with LTL in female newborns (β = -1.42 × 10 -4 , P = .022). 13% of the effect of PFOS on female LTL was mediated through ROS approximately by the mediation analyses. However, in male newborns, no relationships among PFASs, ROS and LTL were observed. Our findings suggest a "programming" role of PFASs on fetal telomere biology system in females in intrauterine stage. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Investigation of antigen-antibody interactions of sulfonamides with a monoclonal antibody in a fluorescence polarization immunoassay using 3D-QSAR models

    Science.gov (United States)

    A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular si...

  13. Distribution of sulfonamide resistance genes in Escherichia coli and Salmonella isolates from swine and chickens at abattoirs in Ontario and Québec, Canada.

    Science.gov (United States)

    Kozak, Gosia K; Pearl, David L; Parkman, Julia; Reid-Smith, Richard J; Deckert, Anne; Boerlin, Patrick

    2009-09-01

    Sulfonamide-resistant Escherichia coli and Salmonella isolates from pigs and chickens in Ontario and Québec were screened for sul1, sul2, and sul3 by PCR. Each sul gene was distributed differently across populations, with a significant difference between distribution in commensal E. coli and Salmonella isolates and sul3 restricted mainly to porcine E. coli isolates.

  14. Distribution of Sulfonamide Resistance Genes in Escherichia coli and Salmonella Isolates from Swine and Chickens at Abattoirs in Ontario and Québec, Canada ▿

    Science.gov (United States)

    Kozak, Gosia K.; Pearl, David L.; Parkman, Julia; Reid-Smith, Richard J.; Deckert, Anne; Boerlin, Patrick

    2009-01-01

    Sulfonamide-resistant Escherichia coli and Salmonella isolates from pigs and chickens in Ontario and Québec were screened for sul1, sul2, and sul3 by PCR. Each sul gene was distributed differently across populations, with a significant difference between distribution in commensal E. coli and Salmonella isolates and sul3 restricted mainly to porcine E. coli isolates. PMID:19633109

  15. Generic penetration in the retail atypical antipsychotic market.

    Science.gov (United States)

    Lenderts, Susan; Kalali, Amir H; Buckley, Peter

    2010-03-01

    In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

  16. Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources?

    DEFF Research Database (Denmark)

    Hu, Xindi C; Dassuncao, Clifton; Zhang, Xianming

    2018-01-01

    BACKGROUND: Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine detection of more than 15 PFASs in human sera, allowing better profiling of PFAS......) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects. METHODS: We use available PFAS concentrations from several demographic groups in a North Atlantic seafood consuming population (Faroe Islands...... sulfonamidoacetate (N-EtFOSAA), which are directly used or metabolized from fluorochemicals in consumer products such as carpet and food packaging. We find that the same compounds are associated with the same exposure sources in two North American populations, suggesting generalizability of results from the Faroese...

  17. Association between perfluoroalkyl substance exposure and asthma and allergic disease in children as modified by MMR vaccination

    DEFF Research Database (Denmark)

    Timmermann, Clara Amalie Gade; Budtz-Jørgensen, Esben; Jensen, Tina Kold

    2017-01-01

    Perfluoroalkyl substances (PFASs) are highly persistent chemicals that might be associated with asthma and allergy, but the associations remain unclear. Therefore, this study examined whether pre- and postnatal PFAS exposure was associated with childhood asthma and allergy. Measles, mumps......, and rubella (MMR) vaccination in early life may have a protective effect against asthma and allergy, and MMR vaccination is therefore taken into account when evaluating these associations. In a cohort of Faroese children whose mothers were recruited during pregnancy, serum concentrations of five PFASs...... with immunoglobulin E (IgE) (cord blood and at age 7 years) and asthma/allergic diseases (questionnaires at ages 5 and 13 years and skin prick test at age 13 years) was determined. A total of 559 children were included in the analyses. Interactions with MMR vaccination were evaluated. Among 22 MMR...

  18. A review of contamination of surface-, ground-, and drinking water in Sweden by perfluoroalkyl and polyfluoroalkyl substances (PFASs).

    Science.gov (United States)

    Banzhaf, Stefan; Filipovic, Marko; Lewis, Jeffrey; Sparrenbom, Charlotte J; Barthel, Roland

    2017-04-01

    Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are found in aquatic systems, flora, and fauna worldwide. These potentially harmful compounds are also frequently detected in Sweden and have already resulted in severe problems for public drinking water supply, i.e., some wells had to be closed due to high PFAS concentrations both in raw water and produced drinking water. Knowledge on PFAS occurrence in Sweden is still quite low, although monitoring is currently ongoing. This work describes potential sources for PFASs to enter the drinking water supply in Sweden and compares different occurrences of PFASs in raw and drinking water in the country. Moreover, the monitoring history, the legal situation, and remediation actions taken are presented. Finally, future challenges and the way forward in Sweden are discussed.

  19. 40 CFR 721.9973 - Zirconium dichlorides (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Zirconium dichlorides (generic). 721... Substances § 721.9973 Zirconium dichlorides (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as zirconium dichlorides (PMNs P...

  20. 40 CFR 721.2083 - Polysubstituted carbomonocyclic hydroxylamine (generic).

    Science.gov (United States)

    2010-07-01

    ... hydroxylamine (generic). 721.2083 Section 721.2083 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Specific Chemical Substances § 721.2083 Polysubstituted carbomonocyclic hydroxylamine (generic). (a... generically as a polysubstituted carbomonocyclic hydroxylamine (PMN P-97-878) is subject to reporting under...

  1. 40 CFR 721.5350 - Substituted nitrile (generic name).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Substituted nitrile (generic name... Substances § 721.5350 Substituted nitrile (generic name). (a) Chemical substances and significant new uses subject to reporting. (1) The chemical substance identified generically as a substituted nitrile (PMN P-83...

  2. 40 CFR 721.555 - Alkyl amino nitriles (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkyl amino nitriles (generic). 721... Substances § 721.555 Alkyl amino nitriles (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substances identified generically as alkyl amino nitriles (PMNs P-96...

  3. A developmental analysis of generic nouns in Southern Peruvian Quechua.

    Science.gov (United States)

    Mannheim, Bruce; Gelman, Susan A; Escalante, Carmen; Huayhua, Margarita; Puma, Rosalía

    2010-01-01

    Generic noun phrases (e.g., "Cats like to drink milk") are a primary means by which adults express generalizations to children, yet they pose a challenging induction puzzle for learners. Although prior research has established that English speakers understand and produce generic noun phrases by preschool age, little is known regarding the cross-cultural generality of generic acquisition. Southern Peruvian Quechua provides a valuable comparison because, unlike English, it is a highly inflected language in which generics are marked by the absence rather than the presence of any linguistic markers. Moreover, Quechua is spoken in a cultural context that differs markedly from the highly educated, middle-class contexts within which earlier research on generics was conducted. We presented participants from 5 age groups (3-6, 7-9, 10-12, 14-35, and 36-90 years of age) with two tasks that examined the ability to distinguish generic from non-generic utterances. In Study 1, even the youngest children understood generics as applying broadly to a category (like "all") and distinct from indefinite reference ("some"). However, there was a developmental lag before children understood that generics, unlike "all", can include exceptions. Study 2 revealed that generic interpretations are more frequent for utterances that (a) lack specifying markers and (b) are animate. Altogether, generic interpretations are found among the youngest participants, and may be a default mode of quantification. These data demonstrate the cross-cultural importance of generic information in linguistic expression.

  4. 40 CFR 721.9959 - Polyurethane polymer (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Polyurethane polymer (generic). 721... Substances § 721.9959 Polyurethane polymer (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as a polyurethane polymer (PMN P-01...

  5. 40 CFR 721.324 - Alkoxylated acrylate polymer (generic).

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Alkoxylated acrylate polymer (generic... Substances § 721.324 Alkoxylated acrylate polymer (generic). (a) Chemical substance and significant new uses subject to reporting. (1) The chemical substance identified generically as alkoxylated acrylate polymer...

  6. [The patents game. Generic and biosimilar drugs].

    Science.gov (United States)

    Villamañán, E; González, D; Armada, E; Ruano, M; Álvarez-Sala, R; Herrero, A

    2016-01-01

    The protection provided by patents on medicines has a limited duration. The expiry of patents expiration allows copies of the drugs to be released, competing with original. At first, they were identical to the original, known as generic drugs, but in recent years, due to the marketing of biological therapies and the expiry of many of their patents, biosimilar drugs have also emerged. These are not exact copies of the original, but, like generic drugs, biosimilar drugs have to demonstrate equivalence to the reference drugs in quality, safety and efficacy. Nevertheless, despite their importance and contribution to sustainability of health system, doctors are sometimes unaware of differences between them, and their impact in terms of clinical and economic effects. An attempt is made to review and clarify certain aspects often unknown by physicians, despite their involvement in their use. Copyright © 2015 SECA. Published by Elsevier Espana. All rights reserved.

  7. Generic Structure Potential of Christian Apologetics

    Directory of Open Access Journals (Sweden)

    Onwu Inya

    2012-01-01

    Full Text Available Religious texts have been examined by scholars from different theoretical standpoints. However, a close survey of the literature reveals that little attention has been paid to Christian apologetics from a linguistic perspective. Also, an examination of studies along the lines of Generic Structure Potential (henceforth GSP shows that the genre status of Christian apologetics has not been indicated. This gap provides the motivation for this paper, which investigates the GSP of Christian apologetics. Twenty texts written by various key contemporary apologetic writers were purposively selected for the study. The following generic structure potential catalogue was generated:The paper reveals that the elements of the GSP concertedly work to advance, argue for or defend the Christian belief system. The paper also suggests that the model could be applied to other forms of apologetic instances.

  8. Generic Sensor Failure Modeling for Cooperative Systems

    Science.gov (United States)

    Jäger, Georg; Zug, Sebastian

    2018-01-01

    The advent of cooperative systems entails a dynamic composition of their components. As this contrasts current, statically composed systems, new approaches for maintaining their safety are required. In that endeavor, we propose an integration step that evaluates the failure model of shared information in relation to an application’s fault tolerance and thereby promises maintainability of such system’s safety. However, it also poses new requirements on failure models, which are not fulfilled by state-of-the-art approaches. Consequently, this work presents a mathematically defined generic failure model as well as a processing chain for automatically extracting such failure models from empirical data. By examining data of an Sharp GP2D12 distance sensor, we show that the generic failure model not only fulfills the predefined requirements, but also models failure characteristics appropriately when compared to traditional techniques. PMID:29558435

  9. An Internet of Things Generic Reference Architecture

    DEFF Research Database (Denmark)

    Bhalerao, Dipashree M.; Riaz, Tahir; Madsen, Ole Brun

    2013-01-01

    Internet of things Network is a future application of Internet. This network has three major basic blocks as business process or Application, core network or internetwork and peripheral network as Things or objects. The assembly has the basic intention of connecting all physical and virtual things......, and keeping track of all these things for monitoring and controlling some information. IoT architecture is studied from software architecture, overall system architecture and network architecture point of view. Paper puts forward the requirements of software architecture along with, its component...... and deployment diagram, process and interface diagram at abstract level. Paper proposes the abstract generic IoT reference and concrete abstract generic IoT reference architectures. Network architecture is also put up as a state of the art. Paper shortly gives overviews of protocols used for IoT. Some...

  10. Assessment of the Influence of Soil Characteristics and Hydrocarbon Fuel Cocontamination on the Solvent Extraction of Perfluoroalkyl and Polyfluoroalkyl Substances.

    Science.gov (United States)

    Mejia-Avendaño, Sandra; Munoz, Gabriel; Sauvé, Sébastien; Liu, Jinxia

    2017-02-21

    Sites impacted by the use of aqueous film-forming foams (AFFFs) present elevated concentrations of perfluoroalkyl and polyfluoroalkyl substances (PFAS). The characterization of the PFAS contamination at such sites may be greatly complicated by the presence of hydrocarbon cocontaminants and by the large variety of PFAS potentially present in AFFFs. In order to further a more comprehensive characterization of AFFF-contaminated soils, the solvent extraction of PFAS from soil was studied under different conditions. Specifically, the impact of soil properties (textural class, organic matter content) and the presence of hydrocarbon contamination (supplemented in the form of either diesel or crude oil) on PFAS recovery performance was evaluated for two extraction methods [methanol/sodium hydroxide (MeOH/NaOH) and methanol/ammonium hydroxide (MeOH/NH 4 OH)]. While both methods performed satisfactorily for perfluoroalkyl acids and fluorotelomer sulfonates, the extraction of newly identified surfactants with functionalities such as betaine and quaternary ammonium was improved with the MeOH/NaOH based method. The main factors that were found to influence the extraction efficiency were the soil properties; a high organic matter or clay content was observed to negatively affect the recovery of the newly identified compounds. While the MeOH/NaOH solvent yielded more efficient recovery rates overall, it also entailed the disadvantage of presenting higher detection limits and substantial matrix effects at the instrumental analysis stage, requiring matrix-matched calibration curves. The results discussed herein bear important implications for a more comprehensive and reliable environmental monitoring of PFAS components at AFFF-impacted sites.

  11. U.S. NRC's generic issues program

    International Nuclear Information System (INIS)

    Kauffman, J.V.; Foster, J.W.

    2008-01-01

    The United States Nuclear Regulatory Commission (NRC) has a Generic Issues Program (GIP) to address Generic Issues (GI). A GI is defined as 'a regulatory matter involving the design, construction, operation, or decommissioning of several, or a class of, NRC licensees or certificate holders that is not sufficiently addressed by existing rules, guidance, or programs'. This rather legalistic definition has several practical corollaries: First, a GI must involve safety. Second, the issue must involve at least two plants, or it would be a plant-specific issue rather than a GI. Third, the potential safety question must not be covered by existing regulations and guidance (compliance). Thus, the effect of a GI is to potentially change the body of regulations and associated guidance (e.g., regulatory guides). The GIP was started in 1976, thus it is a relatively mature program. Approximately 850 issues have been processed by the program to date. More importantly, even after 30 years, new GIs continue to be proposed. The entire set of Generic Issues (GIs) is updated annually in NUREG-0933, 'A Prioritization of Generic Safety Issues'. GIs normally involve complex questions of safety and regulation. Efficient and effective means of addressing these issues are very important for regulatory effectiveness. If an issue proves to pose a genuine, significant safety question, then swift, effective, enforceable, and cost-effective action needs to be taken. Conversely, if an issue is of little safety significance, the issue should be dismissed in an expeditious manner, avoiding unnecessary expenditure of resources and regulatory burden or uncertainty. This paper provides a summary of the 5-stage program, from identification through the regulatory assessment stage. The paper also includes a discussion of the program's seven criteria, sources of proposed GIs, recent improvements, publicly available information, historical performance, and status of current GIs. (authors)

  12. Molten salts processes and generic simulation

    International Nuclear Information System (INIS)

    Ogawa, Toru; Minato, Kazuo

    2001-01-01

    Development of dry separation process (pyrochemical process) using molten salts for the application of spent-nuclear fuel reprocessing requires a rather complete fundamental database as well as process simulation technique with wide applicability. The present report concerns recent progress and problems in this field taking behaviors of co-electrodeposition of UO 2 and PuO 2 in molten salts as an example, and using analytical simulation of local equilibrium combined with generic diffusion. (S. Ohno)

  13. Savannah River Site generic data base development

    International Nuclear Information System (INIS)

    Blanchard, A.

    2000-01-01

    This report describes the results of a project to improve the generic component failure database for the Savannah River Site (SRS). Additionally, guidelines were developed further for more advanced applications of database values. A representative list of components and failure modes for SRS risk models was generated by reviewing existing safety analyses and component failure data bases and from suggestions from SRS safety analysts. Then sources of data or failure rate estimates were identified and reviewed for applicability. A major source of information was the Nuclear Computerized Library for Assessing Reactor Reliability, or NUCLARR. This source includes an extensive collection of failure data and failure rate estimates for commercial nuclear power plants. A recent Idaho National Engineering Laboratory report on failure data from the Idaho Chemical Processing Plant was also reviewed. From these and other recent sources, failure data and failure rate estimates were collected for the components and failure modes of interest. For each component failure mode, this information was aggregated to obtain a recommended generic failure rate distribution (mean and error factor based on a lognormal distribution). Results are presented in a table in this report. A major difference between generic database and previous efforts is that this effort estimates failure rates based on actual data (failure events) rather than on existing failure rate estimates. This effort was successful in that over 75% of the results are now based on actual data. Also included is a section on guidelines for more advanced applications of failure rate data. This report describes the results of a project to improve the generic component failure database for the Savannah River site (SRS). Additionally, guidelines were developed further for more advanced applications of database values

  14. Molten salts processes and generic simulation

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Toru; Minato, Kazuo [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2001-12-01

    Development of dry separation process (pyrochemical process) using molten salts for the application of spent-nuclear fuel reprocessing requires a rather complete fundamental database as well as process simulation technique with wide applicability. The present report concerns recent progress and problems in this field taking behaviors of co-electrodeposition of UO{sub 2} and PuO{sub 2} in molten salts as an example, and using analytical simulation of local equilibrium combined with generic diffusion. (S. Ohno)

  15. Agricultural Market Structure, Generic Advertising, and Welfare

    OpenAIRE

    Cardon, James H.; Pope, Rulon D.

    2003-01-01

    This analysis begins with a definition and discussion of productive advertising. Then, following Dixit and Norman, persuasive advertising is used to study the welfare effects of generic advertising by marketing orders. The study first examines horizontal competition when the competing advertiser is a monopoly, and results show that the socially optimal level of advertising for a competitive marketing order is positive only if advertising raises monopoly output. Next, advertising choices of a ...

  16. C18-coated stir bar sorptive extraction combined with high performance liquid chromatography-electrospray tandem mass spectrometry for the analysis of sulfonamides in milk and milk powder.

    Science.gov (United States)

    Yu, Chunhe; Hu, Bin

    2012-02-15

    A simple, rapid, sensitive, inexpensive and less sample consuming method of C(18)-stir bar sorptive extraction (SBSE)-high performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) was proposed for the determination of six sulfonamides in milk and milk powder samples. C(18) silica particles coated stir bar was prepared by adhesion method, and two kinds of adhesive glue, polydimethylsiloxane (PDMS) sol and epoxy glue were tried. It was found that the C(18)-coated stir bar prepared by PDMS sol as adhesive glue is more robust than that prepared by epoxy glue when liquid desorption was employed, in terms of both lifetime and organic solvent tolerance. The preparation of C(18) stir bar was simple with good mechanic strength and the stir bar could be reused for more than 20 times. Granular coating has relatively high specific surface area and is propitious to sorptive extraction based process. Compared to conventional PDMS SBSE coating, C(18) coating shows good affinity to the target polar/weak polar sulfonamides. To achieve optimum SBSE extraction performance, several parameters including extraction and desorption time, ionic strength, sample pH and stirring speed were investigated. The detection limits of the proposed method for six sulfonamides were in the range of 0.9-10.5 μg/L for milk and 2.7-31.5 μg/kg for milk powder. Good linearities were obtained for sulfonamides with the correlation coefficients (R) above 0.9922. Finally, the proposed method was successfully applied to the determination of sulfonamides in milk and milk powder samples and satisfied recoveries of spiked target compounds in real samples were obtained. Copyright © 2012 Elsevier B.V. All rights reserved.

  17. Generic superweak chaos induced by Hall effect

    Science.gov (United States)

    Ben-Harush, Moti; Dana, Itzhack

    2016-05-01

    We introduce and study the "kicked Hall system" (KHS), i.e., charged particles periodically kicked in the presence of uniform magnetic (B ) and electric (E ) fields that are perpendicular to each other and to the kicking direction. We show that for resonant values of B and E and in the weak-chaos regime of sufficiently small nonintegrability parameter κ (the kicking strength), there exists a generic family of periodic kicking potentials for which the Hall effect from B and E significantly suppresses the weak chaos, replacing it by "superweak" chaos (SWC). This means that the system behaves as if the kicking strength were κ2 rather than κ . For E =0 , SWC is known to be a classical fingerprint of quantum antiresonance, but it occurs under much less generic conditions, in particular only for very special kicking potentials. Manifestations of SWC are a decrease in the instability of periodic orbits and a narrowing of the chaotic layers, relative to the ordinary weak-chaos case. Also, for global SWC, taking place on an infinite "stochastic web" in phase space, the chaotic diffusion on the web is much slower than the weak-chaos one. Thus, the Hall effect can be relatively stabilizing for small κ . In some special cases, the effect is shown to cause ballistic motion for almost all parameter values. The generic global SWC on stochastic webs in the KHS appears to be the two-dimensional closest analog to the Arnol'd web in higher dimensional systems.

  18. Generic legislation of new psychoactive drugs.

    Science.gov (United States)

    van Amsterdam, Jan; Nutt, David; van den Brink, Wim

    2013-03-01

    New psychoactive drugs (NPDs, new psychoactive substances) enter the market all the time. However, it takes several months to ban these NPDs and immediate action is generally not possible. Several European countries and drug enforcement officers insist on a faster procedure to ban NPDs. Introduction of generic legislation, in which clusters of psychotropic drugs are banned in advance, has been mentioned as a possible solution. Here we discuss the pros and cons of such an approach. First, generic legislation could unintentionally increase the expenditures of enforcement, black market practices, administrative burden and health risks for users. Second, it may have a negative impact on research and the development of new treatments. Third, due to the complexity of generic legislation, problems in the enforcement are anticipated due to lack of knowledge about the chemical nomenclature. Finally, various legal options are already available to ban the use, sale and trade of NPDs. We therefore conclude that the currently used scientific benefit-risk evaluation should be continued to limit the adverse health effects of NPDs. Only in emergency cases, where fatal incidents (may) occur, should this approach be overruled.

  19. Generic programming for deterministic neutron transport codes

    International Nuclear Information System (INIS)

    Plagne, L.; Poncot, A.

    2005-01-01

    This paper discusses the implementation of neutron transport codes via generic programming techniques. Two different Boltzmann equation approximations have been implemented, namely the Sn and SPn methods. This implementation experiment shows that generic programming allows us to improve maintainability and readability of source codes with no performance penalties compared to classical approaches. In the present implementation, matrices and vectors as well as linear algebra algorithms are treated separately from the rest of source code and gathered in a tool library called 'Generic Linear Algebra Solver System' (GLASS). Such a code architecture, based on a linear algebra library, allows us to separate the three different scientific fields involved in transport codes design: numerical analysis, reactor physics and computer science. Our library handles matrices with optional storage policies and thus applies both to Sn code, where the matrix elements are computed on the fly, and to SPn code where stored matrices are used. Thus, using GLASS allows us to share a large fraction of source code between Sn and SPn implementations. Moreover, the GLASS high level of abstraction allows the writing of numerical algorithms in a form which is very close to their textbook descriptions. Hence the GLASS algorithms collection, disconnected from computer science considerations (e.g. storage policy), is very easy to read, to maintain and to extend. (authors)

  20. Generic Switching and Non-Persistence among Medicine Users

    DEFF Research Database (Denmark)

    Østergaard Rathe, Jette; Andersen, Morten; Jarbøl, Dorte Ejg

    2015-01-01

    BACKGROUND: Generic substitution means that one medicinal product is replaced by another product containing the same active substance. It is strictly regulated with respect to its bioequivalence, and all products must have undergone appropriate studies. Although generic substitution is widely...... implemented, it still remains to be answered how generic switch influences persistence to long-term treatment, and if it is modified by patients' concerns about medicine and views on generic medicine. This study focuses on users of antidepressants and antiepileptics, and their experience of generic switching....... METHODS: The study was an observational cohort study. By use of a prescription database, we identified patients who had redeemed prescriptions on generically substitutable drugs, and a questionnaire was mailed to them. We analyzed predictors of discontinuation in relation to generic switch and patients...

  1. Advances on generic exemption levels and generic clearance levels in the argentinean regulatory field

    International Nuclear Information System (INIS)

    Muñiz, C.C.; Bossio, M.C.

    2011-01-01

    With the aim of optimizing the regulatory effort in Argentina, the Nuclear Regulatory Authority (ARN) evaluated two worldwide concepts used in the radioactive waste management field: “Generic Exemption Levels” and “Generic Clearance Levels”. The objective of this paper is to present the progress made in the past two years in relation to these topics and to present the results of the specific requests received from users of radioactive material. Since the approval of both Generic Levels, the ARN received two exemption requests. The first one, regarding the practice of dismantling lighting rods with 241 Am. The other case regards the international trade, distribution, usage and final disposal of lighting products with radioactive material ( 85 Kr and 232 Th). Concerning clearance, there has not been any request yet. However, in the future the ARN expects to receive this kind of requests from nuclear power plants and other facilities related to the nuclear fuel cycle. (authors) [es

  2. A generic coordinate system and a set of generic variables for MFE database

    International Nuclear Information System (INIS)

    Miner, W.H. Jr.; Ross, D.W.; Solano, E.R.; Valanju, P.M.; Wiley, J.C.

    1993-01-01

    Over the last several years, profile data from nine different tokamaks have been stored in the magnetic fusion energy database (MFEDB). These data sets have come from a variety of sources and most are given in different coordinate systems. In order to attempt any intermachine analysis, it is convenient to transform these data sets into one generic coordinate system and to choose a uniform set of variable names. The authors describe the data sets from each tokamak indicating the source of the data and the coordinate system in which it is given. Next, they discuss the generic coordinate that has been adopted and show how it is implemented for each tokamak. Finally, the generic naming convention that has been adopted is discussed. It follows closely that which was used by Christiansen et al. for the ITER Global Energy Confinement H-Mode Database. For further clarification, they discuss the characteristics of the magnetic geometry given a Fourier representation of the magnetic equilibria

  3. Synthesis of chiral pyrazolo[4,3-e][1,2,4]triazine sulfonamides with tyrosinase and urease inhibitory activity.

    Science.gov (United States)

    Mojzych, Mariusz; Tarasiuk, Paweł; Kotwica-Mojzych, Katarzyna; Rafiq, Muhammad; Seo, Sung-Yum; Nicewicz, Michał; Fornal, Emilia

    2017-12-01

    A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine with chiral amino group has been synthesized and characterized. The compounds were tested for their tyrosinase and urease inhibitory activity. Evaluation of prepared derivatives demonstrated that compounds (8b) and (8j) are most potent mushroom tyrosinase inhibitors whereas all of the obtained compounds showed higher urease inhibitory activity than the standard thiourea. The compounds (8a), (8f) and (8i) exhibited excellent enzyme inhibitory activity with IC 50 0.037, 0.044 and 0.042 μM, respectively, while IC 50 of thiourea is 20.9 μM.

  4. Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Garzan, Atefeh; Willby, Melisa J.; Green, Keith D.; Gajadeera, Chathurada S.; Hou, Caixia; Tsodikov, Oleg V.; Posey, James E.; Garneau-Tsodikova, Sylvie

    2016-12-08

    A two-drug combination therapy where one drug targets an offending cell and the other targets a resistance mechanism to the first drug is a time-tested, yet underexploited approach to combat or prevent drug resistance. By high-throughput screening, we identified a sulfonamide scaffold that served as a pharmacophore to generate inhibitors of Mycobacterium tuberculosis acetyltransferase Eis, whose upregulation causes resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN) in Mycobacterium tuberculosis. Rational systematic derivatization of this scaffold to maximize Eis inhibition and abolish the Eis-mediated KAN resistance of M. tuberculosis yielded several highly potent agents. A crystal structure of Eis in complex with one of the most potent inhibitors revealed that the inhibitor bound Eis in the AG-binding pocket held by a conformationally malleable region of Eis (residues 28–37) bearing key hydrophobic residues. These Eis inhibitors are promising leads for preclinical development of innovative AG combination therapies against resistant TB.

  5. Consumer choice between common generic and brand medicines in a country with a small generic market.

    Science.gov (United States)

    Fraeyman, Jessica; Peeters, Lies; Van Hal, Guido; Beutels, Philippe; De Meyer, Guido R Y; De Loof, Hans

    2015-04-01

    Generic medicines offer an opportunity for governments to contain pharmaceutical expenditures, since generics are generally 10%-80% lower in price than brand medicines. Belgium has a small generic market that takes up 15% of the total pharmaceutical market in packages sold. To determine the knowledge of consumers about the different available packages of a common over-the-counter medicine (acetaminophen) with regard to price advantage, quality, and effectiveness in a country with a small generic market. We conducted an online survey in the general Flemish population using a questionnaire with 25 statements. The questionnaire also contained 2 informative interventions. First, we showed the price per package and per tablet that the patient would pay in the pharmacy. Second, we provided the respondent with general information about generic medication (equivalence, effectiveness, price, and recognition). Before and after the interventions, we probed for preferences and knowledge about the different packages. Multivariate logistic models were used to examine the independent effects of consumer characteristics on responses to the survey statements. We obtained a sample of 1,636 respondents. The general attitude towards generic medication was positive-only 5% would rather not use a generic. Nevertheless, only 17% of the respondents were able to recognize a generic medicine. Older consumers (aged 60 years and above) were more often confused about the different packages (OR = 2.59, 95% CI = 1.76-3.80, P ≤ 0.001). Consumers without a higher education degree tended to be more doubtful about the difference in effectiveness and quality between the different brands (OR = 0.59, 95% CI = 0.44-0.79, P ≤ 0.001). Consumer recognition of the name of the active substance of acetaminophen was poor. When different brands were displayed, possible price advantage seemed to be an important motive to switch to a cheaper brand. Consumers generally found medicines

  6. Effect of biochar amendment on the control of soil sulfonamides, antibiotic-resistant bacteria, and gene enrichment in lettuce tissues

    International Nuclear Information System (INIS)

    Ye, Mao; Sun, Mingming; Feng, Yanfang; Wan, Jinzhong; Xie, Shanni; Tian, Da; Zhao, Yu; Wu, Jun; Hu, Feng; Li, Huixin; Jiang, Xin

    2016-01-01

    Highlights: • Biochar can prevent soil sulfonamides from accumulating in lettuce tissues. • ARB enrichment in lettuce tissues decreased significantly after biochar amendment. • Impedance effect of biochar addition on soil ARGs was also quite effective. • Biochar application can be a practical strategy to protect vegetable safety. - Abstract: Considering the potential threat of vegetables growing in antibiotic-polluted soil with high abundance of antibiotic-resistant genes (ARGs) against human health through the food chain, it is thus urgent to develop novel control technology to ensure vegetable safety. In the present work, pot experiments were conducted in lettuce cultivation to assess the impedance effect of biochar amendment on soil sulfonamides (SAs), antibiotic-resistant bacteria (ARB), and ARG enrichment in lettuce tissues. After 100 days of cultivation, lettuce cultivation with biochar amendment exhibited the greatest soil SA dissipation as well as the significant improvement of lettuce growth indices, with residual soil SAs mainly existing as the tightly bound fraction. Moreover, the SA contents in roots and new/old leaves were reduced by one to two orders of magnitude compared to those without biochar amendment. In addition, isolate counts for SA-resistant bacterial endophytes in old leaves and sul gene abundances in roots and old leaves also decreased significantly after biochar application. However, neither SA resistant bacteria nor sul genes were detected in new leaves. It was the first study to demonstrate that biochar amendment can be a practical strategy to protect lettuce safety growing in SA-polluted soil with rich ARB and ARGs.

  7. Multi-component analysis of tetracyclines, sulfonamides and tylosin in swine manure by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Jacobsen, Anne Marie; Halling-Sørensen, Bent

    2006-03-01

    A multi-component method focussing on thorough sample preparation has been developed for simultaneous analysis of swine manure for three classes of antibiotic-tetracyclines, sulfonamides, and tylosin. Liquid manure was initially freeze-dried and homogenised by pulverization before extraction by pressurised liquid extraction. The extraction was performed at 75 degrees C and 2,500 psig in three steps using two cycles with 0.2 mol L(-1) citric acid buffer (pH 4.7) and one cycle with a mixture of 80% methanol with 0.2 mol L(-1) citric acid (pH 3). After liquid-liquid extraction with heptane to remove lipids, the pH of the manure was adjusted to 3 with formic acid and the sample was vacuum-filtered through 0.6 mum glass-fibre filters. Finally the samples were pre-concentrated by tandem SPE (SAX-HLB). Recoveries were determined for manure samples spiked at three concentrations (50-5,000 microg kg(-1) dry matter); quantification was achieved by matrix-matched calibration. Recoveries were >70% except for oxytetracycline (42-54%), sulfadiazine (59-73%), and tylosin (9-35%) and did not vary with concentration or from day-to-day. Limits of quantification (LOQ) for all compounds, determined as a signal-to-noise ratio of 10, were in the range 10-100 microg kg(-1) dry matter. The suitability of the method was assessed by analysis of swine manure samples from six different pig-production sites, e.g. finishing pigs, sows, or mixed production. Residues of antibiotics were detected in all samples. The largest amounts were found for tetracyclines (up to 30 mg kg(-1) dry matter for the sum of CTC and ECTC). Sulfonamides were detected at concentrations up to 2 mg kg(-1) dry matter (SDZ); tylosin was not detected in any samples.

  8. Determination of six sulfonamide antibiotics, two metabolites and trimethoprim in wastewater by isotope dilution liquid chromatography/tandem mass spectrometry.

    Science.gov (United States)

    Le-Minh, Nhat; Stuetz, Richard M; Khan, Stuart J

    2012-01-30

    A highly sensitive method for the analysis of six sulfonamide antibiotics (sulfadiazine, sulfathiazole, sulfapyridine, sulfamerazine, sulfamethazine and sulfamethoxazole), two sulfonamide metabolites (N(4)-acetyl sulfamethazine and N(4)-acetyl sulfamethoxazole) and the commonly co-applied antibiotic trimethoprim was developed for the analysis of complex wastewater samples. The method involves solid phase extraction of filtered wastewater samples followed by liquid chromatography-tandem mass spectral detection. Method detection limits were shown to be matrix-dependent but ranged between 0.2 and 0.4 ng/mL for ultrapure water, 0.4 and 0.7 ng/mL for tap water, 1.4 and 5.9 ng/mL for a laboratory-scale membrane bioreactor (MBR) mixed liquor, 0.7 and 1.7 ng/mL for biologically treated effluent and 0.5 and 1.5 ng/g dry weight for MBR activated sludge. An investigation of analytical matrix effects was undertaken, demonstrating the significant and largely unpredictable nature of signal suppression observed for variably complex matrices compared to an ultrapure water matrix. The results demonstrate the importance of accounting for such matrix effects for accurate quantitation, as done in the presented method by isotope dilution. Comprehensive validation of calibration linearity, reproducibility, extraction recovery, limits of detection and quantification are also presented. Finally, wastewater samples from a variety of treatment stages in a full-scale wastewater treatment plant were analysed to illustrate the effectiveness of the method. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Effect of biochar amendment on the control of soil sulfonamides, antibiotic-resistant bacteria, and gene enrichment in lettuce tissues

    Energy Technology Data Exchange (ETDEWEB)

    Ye, Mao [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China); Sun, Mingming [Soil Ecology Lab, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Feng, Yanfang, E-mail: fengyanfang@163.com [Institute of Agricultural Resources and Environment, Jiangsu Academy of Agricultural Sciences, Nanjing 210014 (China); Wan, Jinzhong [Nanjing Institute of Environmental Science, Ministry of Environmental Protection of China, Nanjing 210042 (China); Xie, Shanni; Tian, Da [Soil Ecology Lab, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Zhao, Yu [Collaborative Innovation Center of Advanced Microstructures, Jiangsu Provincial Key Laboratory of Photonic and Electronic Materials, School of Electronic Science and Engineering, Nanjing University, Nanjing 210093 (China); Wu, Jun; Hu, Feng; Li, Huixin [Soil Ecology Lab, College of Resources and Environmental Sciences, Nanjing Agricultural University, Nanjing 210095 (China); Jiang, Xin, E-mail: Jiangxin@issas.ac.cn [State Key Laboratory of Soil and Sustainable Agriculture, Institute of Soil Science, Chinese Academy of Sciences, Nanjing 210008 (China)

    2016-05-15

    Highlights: • Biochar can prevent soil sulfonamides from accumulating in lettuce tissues. • ARB enrichment in lettuce tissues decreased significantly after biochar amendment. • Impedance effect of biochar addition on soil ARGs was also quite effective. • Biochar application can be a practical strategy to protect vegetable safety. - Abstract: Considering the potential threat of vegetables growing in antibiotic-polluted soil with high abundance of antibiotic-resistant genes (ARGs) against human health through the food chain, it is thus urgent to develop novel control technology to ensure vegetable safety. In the present work, pot experiments were conducted in lettuce cultivation to assess the impedance effect of biochar amendment on soil sulfonamides (SAs), antibiotic-resistant bacteria (ARB), and ARG enrichment in lettuce tissues. After 100 days of cultivation, lettuce cultivation with biochar amendment exhibited the greatest soil SA dissipation as well as the significant improvement of lettuce growth indices, with residual soil SAs mainly existing as the tightly bound fraction. Moreover, the SA contents in roots and new/old leaves were reduced by one to two orders of magnitude compared to those without biochar amendment. In addition, isolate counts for SA-resistant bacterial endophytes in old leaves and sul gene abundances in roots and old leaves also decreased significantly after biochar application. However, neither SA resistant bacteria nor sul genes were detected in new leaves. It was the first study to demonstrate that biochar amendment can be a practical strategy to protect lettuce safety growing in SA-polluted soil with rich ARB and ARGs.

  10. Purification and inhibition studies with anions and sulfonamides of an α-carbonic anhydrase from the Antarctic seal Leptonychotes weddellii.

    Science.gov (United States)

    Cincinelli, Alessandra; Martellini, Tania; Innocenti, Alessio; Scozzafava, Andrea; Supuran, Claudiu T

    2011-03-15

    A high activity α-carbonic anhydrase (CA, EC 4.2.1.1) has been purified from various tissues of the Antarctic seal Leptonychotes weddellii. The new enzyme, denominated lwCA, has a catalytic activity for the physiologic CO(2) hydration to bicarbonate reaction, similar to that of the high activity human isoform hCA II, with a k(cat) of 1.1×10(6) s(-1), and a k(cat)/K(m) of 1.4×10(8) M(-1) s(-1). The enzyme was highly inhibited by cyanate, thiocyanate, cyanide, bicarbonate, carbonate, as well as sulfamide, sulfamate, phenylboronic/phenylarsonic acids (K(I)s in the range of 46-100 μM). Many clinically used sulfonamides, such as acetazolamide, methazolamide, dorzolamide, brinzolamide and benzolamide were low nanomolar inhibitors, with K(I)s in the range of 5.7-67 nM. Dichlorophenamide, zonisamide, saccharin and hydrochlorothiazide were weaker inhibitors, with K(I)s in the range of 513-5390 nM. The inhibition profile with anions and sulfonamides of the seal enzyme was rather different from those of the human isoforms hCA I and II. The high sensitivity to bicarbonate inhibition of lwCA, unlike that of the human enzymes, may reflect an evolutionary adaptation to the deep water, high CO(2) partial pressure and hypoxic conditions in which Weddell seals spend much of their life. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Generic drugs: myths, facts, and limitations

    Directory of Open Access Journals (Sweden)

    Antonio Marzo

    2012-10-01

    Full Text Available Bioequivalence (BE has always been an important pharmaceutical area, particularly (but not solely in Mediterranean region, where the use of generic drugs is a relatively recent development. The lack of new therapeutic molecules has concentrated primary research in the hands of a few large pharmaceutical companies. For smaller companies, this has created opportunities for the development of new formulations of existing drugs (orodispersible tablets that dissolve in the mouth, extended-release tablets, transdermal delivery systems, generic drugs. These applications take advantage of the Abridged New Drug Application (ANDA procedure, which exempts them from a series of expensive investigations and limits the requirement for clinical testing to bioequivalence trials. Since 1991, bioequivalence trials have been regulated by US Food and Drug Administration (FDA and European Medicines Agency (EMA guidelines that provide precise indications on the most specific procedures to be adopted. In spite of these guidelines, however, some aspects of the process have not been fully defined, the most important of which regards the management of endogenous substances. Additional problems are how to manage bioequivalence protocols with drugs that have long half-lives and those whose clearance is characterized by high intrinsic variability. The view that bioequivalence data would be more reliable if they were based on studies in target populations is a myth to be discredited. The present paper reviews issues relative to pharmacokinetics (PK, bioavailability (BA, and bioequivalence, also from an historical viewpoint, and includes a stimulating “questions and answers” section on some key aspects of the bioequivalence of generic drugs.

  12. Generic evolution of mixing in heterogeneous media

    Science.gov (United States)

    De Dreuzy, J.; Carrera, J.; Dentz, M.; Le Borgne, T.

    2011-12-01

    Mixing in heterogeneous media results from the competition bewteen flow fluctuations and local scale diffusion. Flow fluctuations quickly create concentration contrasts and thus heterogeneity of the concentration field, which is slowly homogenized by local scale diffusion. Mixing first deviates from Gaussian mixing, which represents the potential mixing induced by spreading before approaching it. This deviation fundamentally expresses the evolution of the interaction between spreading and local scale diffusion. We characterize it by the ratio γ of the non-Gaussian to the Gaussian mixing states. We define the Gaussian mixing state as the integrated squared concentration of the Gaussian plume that has the same longitudinal dispersion as the real plume. The non-Gaussian mixing state is the difference between the overall mixing state defined as the integrated squared concentration and the Gaussian mixing state. The main advantage of this definition is to use the full knowledge previously acquired on dispersion for characterizing mixing even when the solute concentration field is highly non Gaussian. Using high precision numerical simulations, we show that γ quickly increases, peaks and slowly decreases. γ can be derived from two scales characterizing spreading and local mixing, at least for large flux-weighted solute injection conditions into classically log-normal Gaussian correlated permeability fields. The spreading scale is directly related to the longitudinal dispersion. The local mixing scale is the largest scale over which solute concentrations can be considered locally uniform. More generally, beyond the characteristics of its maximum, γ turns out to have a highly generic scaling form. Its fast increase and slow decrease depend neither on the heterogeneity level, nor on the ratio of diffusion to advection, nor on the injection conditions. They might even not depend on the particularities of the flow fields as the same generic features also prevail for

  13. Deriving GENERIC from a Generalized Fluctuation Symmetry

    Science.gov (United States)

    Kraaij, Richard; Lazarescu, Alexandre; Maes, Christian; Peletier, Mark

    2018-02-01

    Much of the structure of macroscopic evolution equations for relaxation to equilibrium can be derived from symmetries in the dynamical fluctuations around the most typical trajectory. For example, detailed balance as expressed in terms of the Lagrangian for the path-space action leads to gradient zero-cost flow. We expose a new such fluctuation symmetry that implies GENERIC, an extension of gradient flow where a Hamiltonian part is added to the dissipative term in such a way as to retain the free energy as Lyapunov function.

  14. Might generic OCs create contraceptive price war?

    Science.gov (United States)

    1987-02-01

    Genora 1/35 and 1/50, the 1st generic oral contraceptives (OCs) in the world, are now being marketed in the US. Clinicians interviewed by "Contraceptive Technology Update" (CTU) offer differing opinions as to what this new OC may mean in the marketplace. Products of Rugby Laboratories, the pills are copy products of Ortho Pharmaceutical's ON 1/35 and ON 1/50 formulations. Most clinicians believe that Genora's success or failure in the OC market depends on its eventual retail price. The price difference of $3-$4 may be sufficiently substantial for retailers to charge less for the generic OCs. If that is the case, many doctors may prescribe a pill which will save their patients $4/month. Dr. Mildred Hanson, a Minneapolis gynecologist/obstetrician, feels any cost savings from Genora will have a significant impact on the OC market. She suggests that the less expensive OCs will catch the attention of health maintenance organizations (HMOs) and the business of women who participate in such health plans. Yet James Burns, director of family planning services for the Hartford City Health Department, thinks that even a full-scale retail price war won't have much effect from a clinic standpoint. He reports that clinics are able to obtain contraceptive supplies rather inexpensively through the contracting system. Hanson also expressed doubt over the potential popularity of Genora 1/50 as clinical concerns about the effects of combined OCs on serum lipid levels and carbohydrate metabolism have resulted in a nationwide push toward OCs containing less than 50 micrograms of estrogen. He indicated concern that declines in pharmaceutical house products from pricing competition with generic pills might have a negative impact on contraceptive research and development. Dick Haskitt, director of business planning for Syntex Laboratories, Inc., who will produce the OCs for Rugby, reports that their market research shows that people are very interested in having a generic OC available

  15. The Northeast Utilities generic plant computer system

    International Nuclear Information System (INIS)

    Spitzner, K.J.

    1980-01-01

    A variety of computer manufacturers' equipment monitors plant systems in Northeast Utilities' (NU) nuclear and fossil power plants. The hardware configuration and the application software in each of these systems are essentially one of a kind. Over the next few years these computer systems will be replaced by the NU Generic System, whose prototype is under development now for Millstone III, an 1150 Mwe Pressurized Water Reactor plant being constructed in Waterford, Connecticut. This paper discusses the Millstone III computer system design, concentrating on the special problems inherent in a distributed system configuration such as this. (auth)

  16. Generic Wing-Body Aerodynamics Data Base

    Science.gov (United States)

    Holst, Terry L.; Olsen, Thomas H.; Kwak, Dochan (Technical Monitor)

    2001-01-01

    The wing-body aerodynamics data base consists of a series of CFD (Computational Fluid Dynamics) simulations about a generic wing body configuration consisting of a ogive-circular-cylinder fuselage and a simple symmetric wing mid-mounted on the fuselage. Solutions have been obtained for Nonlinear Potential (P), Euler (E) and Navier-Stokes (N) solvers over a range of subsonic and transonic Mach numbers and angles of attack. In addition, each solution has been computed on a series of grids, coarse, medium and fine to permit an assessment of grid refinement errors.

  17. Specialization of Generic Array Accesses After Inlining

    Directory of Open Access Journals (Sweden)

    Ryohei Tokuda

    2017-02-01

    Full Text Available We have implemented an optimization that specializes type-generic array accesses after inlining of polymorphic functions in the native-code OCaml compiler. Polymorphic array operations (read and write in OCaml require runtime type dispatch because of ad hoc memory representations of integer and float arrays. It cannot be removed even after being monomorphized by inlining because the intermediate language is mostly untyped. We therefore extended it with explicit type application like System F (while keeping implicit type abstraction by means of unique identifiers for type variables. Our optimization has achieved up to 21% speed-up of numerical programs.

  18. Modeling of Generic Slung Load System

    DEFF Research Database (Denmark)

    Bisgaard, Morten; Bendtsen, Jan Dimon; la Cour-Harbo, Anders

    2009-01-01

    This paper presents the result of the modelling and verification of a generic slung load system using a small-scale helicopter. The model is intended for use in simulation, pilot training, estimation, and control. The model is derived using a redundant coordinate formulation based on Gauss...... slackening and tightening as well as aerodynamic coupling between the helicopter and the load. Furthermore, it is shown how the model can be easily used for multi-lift systems either with multiple helicopters or multiple loads. A numerical stabilisation algorithm is introduced and finally the use...... of the model is illustrated through simulations and flight verifications.  ...

  19. Entry decisions in the generic pharmaceutical industry.

    Science.gov (United States)

    Morton, F M

    1999-01-01

    Data on all generic drug entries in the period 1984-1994 are used to estimate which markets heterogeneous potential entrants will decide to enter. I find that organizational experience predicts entry. Firms tend to enter markets with supply and demand characteristics similar to the firm's existing drugs. Larger revenue markets, markets with more hospital sales, and products that treat chronic conditions attract more entry. The simultaneous nature of entry leads to an additional interpretation: specialization is profitable because of the severe risk to profits when a market is "overentered." However, I am unable to make any conclusions about the efficiency of entry decisions.

  20. Developing A Generic Optical Avionic Network

    DEFF Research Database (Denmark)

    Zhang, Jiang; An, Yi; Berger, Michael Stübert

    2011-01-01

    We propose a generic optical network design for future avionic systems in order to reduce the weight and power consumption of current networks on board. A three-layered network structure over a ring optical network topology is suggested, as it can provide full reconfiguration flexibility...... and support a wide range of avionic applications. Segregation can be made on different hierarchies according to system criticality and security requirements. The structure of each layer is discussed in detail. Two network configurations are presented, focusing on how to support different network services...... by such a network. Finally, three redundancy scenarios are discussed and compared....

  1. Generic device controller for accelerator control systems

    International Nuclear Information System (INIS)

    Mariotti, R.; Buxton, W.; Frankel, R.; Hoff, L.

    1987-01-01

    A new distributed intelligence control system has become operational at the AGS for transport, injection, and acceleration of heavy ions. A brief description of the functionality of the physical devices making up the system is given. An attempt has been made to integrate the devices for accelerator specific interfacing into a standard microprocessor system, namely, the Universal Device Controller (UDC). The main goals for such a generic device controller are to provide: local computing power; flexibility to configure; and real time event handling. The UDC assemblies and software are described

  2. Rigidity of complete generic shrinking Ricci solitons

    Science.gov (United States)

    Chu, Yawei; Zhou, Jundong; Wang, Xue

    2018-01-01

    Let (Mn , g , X) be a complete generic shrinking Ricci soliton of dimension n ≥ 3. In this paper, by employing curvature inequalities, the formula of X-Laplacian for the norm square of the trace-free curvature tensor, the weak maximum principle and the estimate of the scalar curvature of (Mn , g) , we prove some rigidity results for (Mn , g , X) . In particular, it is showed that (Mn , g , X) is isometric to Rn or a finite quotient of Sn under a pointwise pinching condition. Moreover, we establish several optimal inequalities and classify those shrinking solitons for equalities.

  3. Generic Patch Inference

    DEFF Research Database (Denmark)

    Andersen, Jesper; Lawall, Julia Laetitia

    2008-01-01

    A key issue in maintaining Linux device drivers is the need to update drivers in response to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spfind, that identifies common changes made...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

  4. The generic Gröbner walk

    DEFF Research Database (Denmark)

    Jensen, Anders Nedergaard; Lauritzen, Niels; Fukuda, Komei

    2005-01-01

    perturbation of this line. This usually involves both time and space demanding arithmetic of integers much larger than the input numbers. In this paper we show how the explicit line may be replaced by a formal line using Robbiano's characterization of group orders on . This gives rise to the generic Gröbner...... walk involving only Gröbner basis conversion over facets and computations with marked polynomials. The infinite precision integer arithmetic is replaced by term order comparisons between (small) integral vectors. This makes it possible to compute with infinitesimal numbers and perturbations...

  5. Influencers of generic drug utilization: A systematic review.

    Science.gov (United States)

    Howard, Jennifer N; Harris, Ilene; Frank, Gavriella; Kiptanui, Zippora; Qian, Jingjing; Hansen, Richard

    2017-08-04

    With an increase in prescription drug spending and rising drug costs there is a need to encourage the use of generic prescription drugs. However, maximizing generic drug use is not possible without the public's positive perception and meeting their informational needs about generic drugs. Thus, improving the public's confidence in, and knowledge of generic drugs on the market is critical. The objective of this systematic review is to examine and evaluate the studies focusing on the nature and extent of key factors influencing generic drug use in the United States in order to help guide policy, education and practice interventions. Using multiple search engines and key word screening criteria, empirical studies published in English between January 1, 2005 and December 31, 2015 were identified. A qualitative synthesis of the evidence identified domains of key factors that influenced generic drug use across studies. Over 3000 citations met the key word screening criteria; 67 of these met inclusion criteria for the systematic review. Seven domains of factors that influence generic drug utilization were identified: 1) patient-related factors, 2) formulary management or cost containment, 3) healthcare policies, 4) promotional activities, 5) educational initiatives, 6) technology, and 7) physician-related factors. Patients, physicians, pharmacists, formulary managers, and policymakers play an important role in generic drug use. Understanding the factors influencing generic drug use can help guide future policy, education, and practice interventions to increase generic drug use. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. A prioritization of generic safety issues

    International Nuclear Information System (INIS)

    Emrit, R.; Riggs, R.; Milstead, W.; Pittman, J.

    1991-07-01

    This report presents the priority rankings for generic safety issues and related to nuclear power plants. The purpose of these rankings is to assist in the timely and efficient allocation of NRC resources for the resolution of those safety issues that have a significant potential for reducing risk. The report focuses on the prioritization of generic safety issues. Issues primarily concerned with the licensing process or environmental protection and not directly related to safety have been excluded from prioritization. The prioritized issues include: TMI Action Plan items under development; previously proposed issues covered by Task Action Plans, except issues designated as Un-resolved Safety Issues (USIs) which had already been assigned high priority; and newly-proposed issues. Future supplements to this report will include the prioritization of additional issues. The safety priority rankings are High, Medium, Low, and Drop and have been assigned on the basis of risk significance estimates, the ratio of risk to costs and other impacts estimated to result if resolutions of the safety issues were implemented, and the consideration of uncertainties and other quantitative or qualitative factors. To the extent practical, estimates are quantitative. 1310 refs

  7. Estimating human exposure to perfluoroalkyl acids via solid food and drinks: Implementation and comparison of different dietary assessment methods.

    Science.gov (United States)

    Papadopoulou, Eleni; Poothong, Somrutai; Koekkoek, Jacco; Lucattini, Luisa; Padilla-Sánchez, Juan Antonio; Haugen, Margaretha; Herzke, Dorte; Valdersnes, Stig; Maage, Amund; Cousins, Ian T; Leonards, Pim E G; Småstuen Haug, Line

    2017-10-01

    Diet is a major source of human exposure to hazardous environmental chemicals, including many perfluoroalkyl acids (PFAAs). Several assessment methods of dietary exposure to PFAAs have been used previously, but there is a lack of comparisons between methods. To assess human exposure to PFAAs through diet by different methods and compare the results. We studied the dietary exposure to PFAAs in 61 Norwegian adults (74% women, average age: 42 years) using three methods: i) by measuring daily PFAA intakes through a 1-day duplicate diet study (separately in solid and liquid foods), ii) by estimating intake after combining food contamination with food consumption data, as assessed by 2-day weighted food diaries and iii) by a Food Frequency Questionnaire (FFQ). We used existing food contamination data mainly from samples purchased in Norway and if not available, data from food purchased in other European countries were used. Duplicate diet samples (n=122) were analysed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) to quantify 15 PFAAs (11 perfluoroalkyl carboxylates and 4 perfluoroalkyl sulfonates). Differences and correlations between measured and estimated intakes were assessed. The most abundant PFAAs in the duplicate diet samples were PFOA, PFOS and PFHxS and the median total intakes were 5.6ng/day, 11ng/day and 0.78ng/day, respectively. PFOS and PFOA concentrations were higher in solid than liquid samples. PFOS was the main contributor to the contamination in the solid samples (median concentration 14pg/g food), while it was PFOA in the liquid samples (median concentrations: 0.72pg/g food). High intakes of fats, oils, and eggs were statistically significantly related to high intakes of PFOS and PFOA from solid foods. High intake of milk and consumption of alcoholic beverages, as well as food in paper container were related to high PFOA intakes from liquid foods. PFOA intakes derived from food diary and FFQ were significantly higher than

  8. The importance of being first: evidence from Canadian generic pharmaceuticals.

    Science.gov (United States)

    Hollis, Aidan

    2002-12-01

    This paper uses pooled cross-section data on Canadian ethical drug sales to examine the effect of entry timing on sales of generic drugs. The data is for all drugs for which the first generic competitor entered during the years 1994-1997. It is found that the first generic entrant has a lasting competitive advantage: being first into the market appears to lead to an increase of around 30% in market share (among generics) over a period of at least 4 years. This finding has considerable implications for the current policy of allowing brandname drug companies to issue pseudo-generic equivalents as a preemptive strike against true generic competitors. Copyright 2002 John Wiley & Sons, Ltd.

  9. Contact Geometry of Hyperbolic Equations of Generic Type

    Directory of Open Access Journals (Sweden)

    Dennis The

    2008-08-01

    Full Text Available We study the contact geometry of scalar second order hyperbolic equations in the plane of generic type. Following a derivation of parametrized contact-invariants to distinguish Monge-Ampère (class 6-6, Goursat (class 6-7 and generic (class 7-7 hyperbolic equations, we use Cartan's equivalence method to study the generic case. An intriguing feature of this class of equations is that every generic hyperbolic equation admits at most a nine-dimensional contact symmetry algebra. The nine-dimensional bound is sharp: normal forms for the contact-equivalence classes of these maximally symmetric generic hyperbolic equations are derived and explicit symmetry algebras are presented. Moreover, these maximally symmetric equations are Darboux integrable. An enumeration of several submaximally symmetric (eight and seven-dimensional generic hyperbolic structures is also given.

  10. Impact of generic substitution decision support on electronic prescribing behavior.

    Science.gov (United States)

    Stenner, Shane P; Chen, Qingxia; Johnson, Kevin B

    2010-01-01

    To evaluate the impact of generic substitution decision support on electronic (e-) prescribing of generic medications. The authors analyzed retrospective outpatient e-prescribing data from an academic medical center and affiliated network for July 1, 2005-September 30, 2008 using an interrupted time-series design to assess the rate of generic prescribing before and after implementing generic substitution decision support. To assess background secular trends, e-prescribing was compared with a concurrent random sample of hand-generated prescriptions. Proportion of generic medications prescribed before and after the intervention, evaluated over time, and compared with a sample of prescriptions generated without e-prescribing. The proportion of generic medication prescriptions increased from 32.1% to 54.2% after the intervention (22.1% increase, 95% CI 21.9% to 22.3%), with no diminution in magnitude of improvement post-intervention. In the concurrent control group, increases in proportion of generic prescriptions (29.3% to 31.4% to 37.4% in the pre-intervention, post-intervention, and end-of-study periods, respectively) were not commensurate with the intervention. There was a larger change in generic prescribing rates among authorized prescribers (24.6%) than nurses (18.5%; adjusted OR 1.38, 95% CI 1.17 to 1.63). Two years after the intervention, the proportion of generic prescribing remained significantly higher for e-prescriptions (58.1%; 95% CI 57.5% to 58.7%) than for hand-generated prescriptions ordered at the same time (37.4%; 95% CI 34.9% to 39.9%) (p<0.0001). Generic prescribing increased significantly in every specialty. Implementation of generic substitution decision support was associated with dramatic and sustained improvements in the rate of outpatient generic e-prescribing across all specialties.

  11. Generic task problem descriptions: Category B, C, and D tasks

    International Nuclear Information System (INIS)

    1978-06-01

    This document contains information relating to Category B, C, and D generic technical activities. The specific information provided for each task includes the reactor type to which the generic issue applies, the NRC division with lead responsibility and a description of the problem to be addressed by the task. Also provided in this document is a listing of Category A generic technical activities and definitions of Priority Categories A, B, C, and D

  12. Guide for generic application of Reliability Centered Maintenance (RCM) recommendations

    International Nuclear Information System (INIS)

    Schwan, C.A.; Toomey, G.E.; Morgan, T.A.; Darling, S.S.

    1991-02-01

    Previously completed reliability centered maintenance (RCM) studies form the basis for developing or refining a preventive maintenance program. This report describes a generic methodology that will help utilities optimize nuclear plant maintenance programs using RCM techniques. This guide addresses the following areas: history of the generic methodology development process, and use of the generic methodology for conducting system-to-system and component-to-component evaluations. 2 refs., 2 figs., 5 tabs

  13. Novel 3-Nitro-1H-1,2,4-triazole-based Amides and Sulfonamides as Potential anti-Trypanosomal Agents

    Science.gov (United States)

    Papadopoulou, Maria V.; Bloomer, William D.; Rosenzweig, Howard S.; Chatelain, Eric; Kaiser, Marcel; Wilkinson, Shane R.; McKenzie, Caroline; Ioset, Jean-Robert

    2012-01-01

    A series of novel 3-nitro-1H-1,2,4-triazole-(and in some cases 2-nitro-1H-imidazole)-based amides and sulfonamides were characterized for their in vitro anti-trypanosomal and antileishmanial activities as well as mammalian toxicity. Out of 36 compounds tested, 29 (mostly 3-nitro-1H-1,2,4-triazoles) displayed significant activity against T. cruzi intracellular amastigotes (IC50 ranging from 28 nM to 3.72 μM) without concomitant toxicity to L6 host cells (selectivity 66 to 2782). Twenty three of these active compounds were more potent (up to 58 fold) than the reference drug benznidazole, tested in parallel. In addition, 9 nitrotriazoles which were moderately active (0.5 μM ≤ IC50 amides and sulfonamides are potent anti-trypanosomal agents. PMID:22550999

  14. Spatial distribution and partitioning behavior of selected poly- and perfluoroalkyl substances in freshwater ecosystems: A French nationwide survey

    Energy Technology Data Exchange (ETDEWEB)

    Munoz, Gabriel; Giraudel, Jean-Luc [University of Bordeaux, EPOC, UMR 5805, LPTC, 351 Cours de la Libération, F-33400 Talence, France. (France); Botta, Fabrizio; Lestremau, François [INERIS, Parc Technologique Alata, BP2, 60550 Verneuil-en-Halatte, France. (France); Dévier, Marie-Hélène [University of Bordeaux, EPOC, UMR 5805, LPTC, 351 Cours de la Libération, F-33400 Talence, France. (France); Budzinski, Hélène [CNRS, EPOC, UMR 5805, LPTC, 351 Cours de la Libération, F-33400 Talence, France. (France); Labadie, Pierre, E-mail: pierre.labadie@u-bordeaux.fr [CNRS, EPOC, UMR 5805, LPTC, 351 Cours de la Libération, F-33400 Talence, France. (France)

    2015-06-01

    The spatial distribution and partitioning of 22 poly- and perfluoroalkyl substances (PFASs) in 133 selected rivers and lakes were investigated at a nationwide scale in mainland France. ΣPFASs was in the range < LOD–725 ng L{sup −1} in the dissolved phase (median: 7.9 ng L{sup −1}) and < LOD–25 ng g{sup −1} dry weight (dw) in the sediment (median: 0.48 ng g{sup −1} dw); dissolved PFAS levels were significantly lower at “reference” sites than at urban, rural or industrial sites. Although perfluorooctane sulfonate (PFOS) was found to be the prevalent compound on average, a multivariate analysis based on neural networks revealed noteworthy trends for other compounds at specific locations and, in some cases, at watershed scale. For instance, several sites along the Rhône River displayed a peculiar PFAS signature, perfluoroalkyl carboxylates (PFCAs) often dominating the PFAS profile (e.g., PFCAs > 99% of ΣPFASs in the sediment, likely as a consequence of industrial point source discharge). Several treatments for data below detection limits (non-detects) were used to compute descriptive statistics, differences among groups, and correlations between congeners, as well as log K{sub d} and log K{sub oc} partition coefficients; in that respect, the Regression on Order Statistics (robust ROS) method was preferred for descriptive statistics computation while the Akritas–Theil–Sen estimator was used for regression and correlation analyses. Multiple regression results suggest that PFAS levels in the dissolved phase and sediment characteristics (organic carbon fraction and grain size) may be significant controlling factors of PFAS levels in the sediment. - Highlights: • A large-scale survey of PFASs in 133 French rivers and lakes is reported. • Descriptive statistics, correlations and partitioning coefficients were determined. • Non-detects were taken into account using functions from the NADA R-package. • Hot spots of PFAS contamination were found

  15. Perfluoroalkyl acids in surface seawater from the North Pacific to the Arctic Ocean: Contamination, distribution and transportation.

    Science.gov (United States)

    Li, Lei; Zheng, Hongyuan; Wang, Tieyu; Cai, Minghong; Wang, Pei

    2018-03-16

    The bioaccumulative, persistent and toxic properties of long-chain perfluoroalkyl acids (PFAAs) resulted in strict regulations on PFAAs, especially in developed countries. Consequently, the industry manufacturing of PFAAs shifts from long-chain to short-chain. In order to better understand the pollution situation of PFAAs in marine environment under this new circumstance, the occurrence of 17 linear PFAAs was investigated in 30 surface seawater samples from the North Pacific to Arctic Ocean (123°E to 24°W, 32 to 82°N) during the sixth Chinese Arctic Expedition in 2014. Total concentrations of PFAAs (∑PFAAs) were between 346.9 pg per liter (pg/L) to 3045.3 pg/L. The average concentrations of ∑PFAAs decreased in the order of East China Sea (2791.4 pg/L, n = 2), Sea of Japan (East Sea) (832.8 pg/L, n = 6), Arctic Ocean (516.9 pg/L, n = 7), Chukchi Sea (505.2 pg/L, n = 4), Bering Sea (501.2 pg/L, n = 8) and Sea of Okhotsk (417.7 pg/L, n = 3). C4 to C9 perfluoroalkyl carboxylic acids (PFCAs) were detected in more than 80% of the surface water samples. Perfluorobutanoic acid (PFBA) was the most prevalent compound and perfluorooctanoic acid (PFOA) was the second abundant homolog. The concentration of individual PFAAs in the surface seawater of East China Sea was much higher than other sampling seas. As the spatial distribution of PFAAs in the marine environment was mainly influenced by the river inflow from the basin countries, which proved the large input from China. Furthermore, the marginal seas of China were found with the greatest burden of PFOA comparing the pollution level in surface seawater worldwide. PFBA concentration in the surrounding seas of China was also high, but distributed more evenly with an obvious increase in recent years. This large-scale monitoring survey will help the improvement and development of PFAAs regulations and management, where production shift should be taken into consideration. Copyright

  16. Can profiles of poly- and Perfluoroalkyl substances (PFASs) in human serum provide information on major exposure sources?

    Science.gov (United States)

    Hu, Xindi C; Dassuncao, Clifton; Zhang, Xianming; Grandjean, Philippe; Weihe, Pál; Webster, Glenys M; Nielsen, Flemming; Sunderland, Elsie M

    2018-02-01

    Humans are exposed to poly- and perfluoroalkyl substances (PFASs) from diverse sources and this has been associated with negative health impacts. Advances in analytical methods have enabled routine detection of more than 15 PFASs in human sera, allowing better profiling of PFAS exposures. The composition of PFASs in human sera reflects the complexity of exposure sources but source identification can be confounded by differences in toxicokinetics affecting uptake, distribution, and elimination. Common PFASs, such as perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS) and their precursors are ubiquitous in multiple exposure sources. However, their composition varies among sources, which may impact associated adverse health effects. We use available PFAS concentrations from several demographic groups in a North Atlantic seafood consuming population (Faroe Islands) to explore whether chemical fingerprints in human sera provide insights into predominant exposure sources. We compare serum PFAS profiles from Faroese individuals to other North American populations to investigate commonalities in potential exposure sources. We compare individuals with similar demographic and physiological characteristics and samples from the same years to reduce confounding by toxicokinetic differences and changing environmental releases. Using principal components analysis (PCA) confirmed by hierarchical clustering, we assess variability in serum PFAS concentrations across three Faroese groups. The first principal component (PC)/cluster consists of C9-C12 perfluoroalkyl carboxylates (PFCAs) and is consistent with measured PFAS profiles in consumed seafood. The second PC/cluster includes perfluorohexanesulfonic acid (PFHxS) and the PFOS precursor N-ethyl perfluorooctane sulfonamidoacetate (N-EtFOSAA), which are directly used or metabolized from fluorochemicals in consumer products such as carpet and food packaging. We find that the same compounds are associated with the same

  17. Encouraging the use of generic medicines: implications for transition economies.

    Science.gov (United States)

    King, Derek R; Kanavos, Panos

    2002-08-01

    Generic drugs have a key role to play in the efficient allocation of financial resources for pharmaceutical medicines. Policies implemented in the countries with a high rate of generic drug use, such as Canada, Denmark, Germany, the Netherlands, the United Kingdom, and the United States, are reviewed, with consideration of the market structures that facilitate strong competition. Savings in these countries are realized through increases in the volume of generic drugs used and the frequently significant differences in the price between generic medicines and branded originator medicines. Their policy tools include the mix of supply-side measures and demand-side measures that are relevant for generic promotion and higher generic use. On the supply-side, key policy measures include generic drug marketing regulation that facilitates market entry soon after patent expiration, reference pricing, the pricing of branded originator products, and the degree of price competition in pharmaceutical markets. On the demand-side, measures typically encompass influencing prescribing and dispensing patterns as well as introducing a co-payment structure for consumers/patients that takes into consideration the difference in cost between branded and generic medicines. Quality of generic medicines is a pre-condition for all other measures discussed to take effect. The paper concludes by offering a list of policy options for decision-makers in Central and Eastern European economies in transition.

  18. Generic substitution of antiretrovirals: patients' and health care providers' opinions.

    Science.gov (United States)

    Kieran, Jennifer A; O'Reilly, Eimear; O'Dea, Siobhan; Bergin, Colm; O'Leary, Aisling

    2017-10-01

    There is interest in introducing generic antiretroviral drugs (ARVs) into high-income countries in order to maximise efficiency in health care budgets. Studies examining patients' and providers' knowledge and attitudes to generic substitution in HIV are few. This was a cross-sectional, observational study with a convenience sample of adult HIV-infected patients and health care providers (HCPs). Data on demographics, knowledge of generic medicine and facilitators of generic substitution were collected. Descriptive and univariate analysis was performed using SPSS V.23™. Questionnaires were completed by 66 patients. Seventy-one per cent would have no concerns with the introduction of generic ARVs. An increase in frequency of administration (61%) or pill burden (53%) would make patients less likely to accept generic ARVs. There were 30 respondents to the HCP survey. Concerns included the supply chain of generics, loss of fixed dose combinations, adherence and use of older medications. An increase in dosing frequency (76%) or an increase in pill burden (50%) would make HCPs less likely to prescribe a generic ARV. The main perceived advantage was financial. Generic substitution of ARVs would be acceptable to the majority of patients and HCPs. Reinvesting savings back into HIV services would facilitate the success of such a programme.

  19. Brand loyalty, patients and limited generic medicines uptake.

    Science.gov (United States)

    Costa-Font, Joan; Rudisill, Caroline; Tan, Stefanie

    2014-06-01

    The sluggish development of European generic drug markets depends heavily on demand side factors, and more specifically, patients' and doctors' loyalty to branded products. Loyalty to originator drugs, to the point where originator prices rise upon generic entry has been described as the 'generics paradox'. Originator loyalty can emerge for a plethora of reasons; including costs, perceptions about quality and physician advice. We know very little about the behavioural underpinnings of brand loyalty from the consumer or patient standpoint. This paper attempts to test the extent to which patients are brand loyal by drawing upon Spain's 2002 Health Barometer survey as it includes questions about consumer acceptance of generics in a country with exceptionally low generic uptake and substitution at the time of the study. Our findings suggest that at least 13% of the population would not accept generics as substitutes to the originator. These results confirm evidence of brand loyalty for a minority. Alongside high levels of awareness of generics, we find that low cost-sharing levels explain consumer brand loyalty but their impact on acceptance of generic substitution is very small. Higher cost-sharing and exempting fewer patients from cost-sharing have the potential to encourage generic acceptance. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Transforming Cobol Legacy Software to a Generic Imperative Model

    National Research Council Canada - National Science Library

    Moraes, DinaL

    1999-01-01

    .... This research develops a transformation system to convert COBOL code into a generic imperative model, recapturing the initial design and deciphering the requirements implemented by the legacy code...