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Sample records for quinolones synthesis potency

  1. Synthesis of Quinolone Analogues:7-[(2S, 4R)-2-Aminomethyl-4- hydroxypyrrolidin-1-yl] Quinolones

    Institute of Scientific and Technical Information of China (English)

    Jiu Yu LIU; Hui Yuan GUO

    2004-01-01

    New quinolone derivatives of 7-[(2S, 4R)-2-aminomethyl-4-hydroxypyrrolidin-1-yl] quinolone-3-carboxylic acids were synthesized by condensation of 7-halo substituted quinolone-3-carboxylic acids with (2S, 4R)-2-aminomethyl-4-hydroxypyrrolidine. These compounds were characterized by FAB-MS and 1H NMR.

  2. Metal-free transannulation reaction of indoles with nitrostyrenes: a simple practical synthesis of 3-substituted 2-quinolones.

    Science.gov (United States)

    Aksenov, Alexander V; Smirnov, Alexander N; Aksenov, Nicolai A; Aksenova, Inna V; Frolova, Liliya V; Kornienko, Alexander; Magedov, Igor V; Rubin, Michael

    2013-10-18

    3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone.

  3. Synthesis and anticancer activity of novel curcumin-quinolone hybrids.

    Science.gov (United States)

    Raghavan, Saiharish; Manogaran, Prasath; Gadepalli Narasimha, Krishna Kumari; Kalpattu Kuppusami, Balasubramanian; Mariyappan, Palanivelu; Gopalakrishnan, Anjana; Venkatraman, Ganesh

    2015-09-01

    A number of new curcumin-quinolone hybrids were synthesised from differently substituted 3-formyl-2-quinolones and vanillin and their in vitro cytotoxicity was determined on a panel of representative cell lines (A549, MCF7, SKOV3 and H460) using MTT assay. The most potent compound 14, was analysed for its mode of action using various cell biology experiments. SKOV3 cells treated with compound 14 showed distorted cell morphology under phase contrast imaging and induction of apoptosis was confirmed by Annexin V/PE assay. Further experiments on generation of reactive oxygen species (ROS) and cell cycle analysis revealed that these hybrids induce apoptosis by ROS generation and arrest cell cycle progression in S and G2/M phase.

  4. Synthesis and in vitro antibacterial activities of 7-(4-alkoxyimino-3-hydroxypiperidin-1-y1)quinolone derivatives

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A series of novel 7-(4-alkoxyimino-3-hydroxypiperidin-1-yl)quinolone derivatives were designed,synthesized and evaluated for in vitro antibacterial activities.Compounds 8f,8g,8i and 8j with the potencies similar to or better than those of levofloxacin and IMB against Staphylococcus aureus and Staphylococcus epidermidis,worth further investigation.

  5. Design and synthesis of modified quinolones as antitumoral acridones.

    Science.gov (United States)

    Tabarrini, O; Cecchetti, V; Fravolini, A; Nocentini, G; Barzi, A; Sabatini, S; Miao, H; Sissi, C

    1999-06-17

    The bacterial topoisomerase II (DNA gyrase) and the mammalian topoisomerase II represent the cellular targets for quinolone antibacterials and a wide variety of anticancer drugs, respectively. In view of the mechanistic similarities and sequence homologies exhibited by the two enzymes, tentative efforts to selectively shift from an antibacterial to an antitumoral activity was made by synthesizing a series of modified tricyclic quinolones, in which the essential 3-carboxylic function is surrogated by phenolic OH and the classic C-6 fluorine atom is replaced by a NH2 group. The resulting 7-amino-9-acridone derivatives were assayed for their antibacterial as well as cytotoxic activities. No antibacterial activity was found. On the other hand, many derivatives showed significant cytotoxic activity against both HL-60 and P388 leukemias and a wide panel of human and rodent solid tumor cells, derivatives 25 and 26 displaying the best overall antiproliferative activity. Against the LoVo cell line, derivative 25 exhibited higher cytotoxic effects than etoposide.

  6. Novel derivatives of benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, and antitumor evaluation.

    Science.gov (United States)

    Dogan Koruznjak, Jasna; Grdisa, Mira; Slade, Neda; Zamola, Branimir; Pavelić, Kresimir; Karminski-Zamola, Grace

    2003-10-01

    Novel derivatives of benzo[b]thieno[2,3-c]quinolones 3a-j were synthesized in a multistep synthesis starting from substituted benzo[b]thiophene-2-carbonyl chlorides, to their corresponding benzo[b]thiophene-2-carboxamides, which were photochemically dehydrohalogenated to their corresponding substituted benzo[b]thieno[2,3-c]quinolones. Compound 4 was prepared from 3i by alkylation with 3-dimethylaminopropyl chloride in the presence of NaH. Compounds 7a,b were prepared from 3g in the multistep synthesis from compounds 5 and 6. Compounds 3b, 3c-f, 3h, 7a, and 7b were found to exert cytostatic activity against malignant cell lines: pancreatic carcinoma (MiaPaCa2), breast carcinoma (MCF7), cervical carcinoma (HeLa), laryngeal carcinoma (Hep2), colon carcinoma (CaCo-2), melanoma (HBL), human fibroblast cell lines (WI-38). The compounds that bear a 3-dimethylaminopropyl substituent on the quinolone nitrogen (3b, 3c-f, 3h) showed higher antitumor activity than compounds bearing the same substituent on the amidic nitrogen (7a and 7b). The compound 3h, which has a 3-dimethylaminopropyl substituent on the quinolone nitrogen and a methoxycarbonyl substituent at position 9, had marked antitumor activity. Because of strong cytotoxic effect of compound 4 on melanoma cells (HBL, ME 67.3, and ME 67.1), a potential mechanism of action was examined. Analysis of DNA and Annexin-V-FLUOS staining indicated that compound 4 causes cell death by apoptosis.

  7. Structural optimization of quinolon-4(1H)-imines as dual-stage antimalarials: toward increased potency and metabolic stability.

    Science.gov (United States)

    Ressurreição, Ana S; Gonçalves, Daniel; Sitoe, Ana R; Albuquerque, Inês S; Gut, Jiri; Góis, Ana; Gonçalves, Lídia M; Bronze, Maria R; Hanscheid, Thomas; Biagini, Giancarlo A; Rosenthal, Philip J; Prudêncio, Miguel; O'Neill, Paul; Mota, Maria M; Lopes, Francisca; Moreira, Rui

    2013-10-10

    Discovery of novel effective and safe antimalarials has been traditionally focused on targeting erythrocytic parasite stages that cause clinical symptoms. However, elimination of malaria parasites from the human population will be facilitated by intervention at different life-cycle stages of the parasite, including the obligatory developmental phase in the liver, which precedes the erythrocytic stage. We have previously reported that N-Mannich-based quinolon-4(1H)-imines are potent antiplasmodial agents but present several stability liabilities. We now report our efforts to optimize quinolon-4(1H)-imines as dual-stage antiplasmodial agents endowed with chemical and metabolic stability. We report compounds active against both the erythrocytic and exoerythrocytic forms of malaria parasites, such as the quinolon-4(1H)-imine 5p (IC50 values of 54 and 710 nM against the erythrocytic and exoerythrocytic forms), which constitute excellent starting points for further lead optimization as dual-stage antimalarials.

  8. Mild and efficient Winterfeldt oxidation of 1,2,3,4-tetrahydro-γ-carbolines for the synthesis of dihydropyrrolo[3,2-b]-quinolones and pyrrolo[3,2-b]quinolones.

    Science.gov (United States)

    Sheng, Rong; Zhu, Jiangwei; Hu, Yongzhou

    2012-01-30

    The Winterfeldt oxidation (NaOH, DMF, air, rt) of substituted 1,2,3,4-tetrahydro-γ-carbolines has been developed, which provides a convenient and efficient method for the synthesis of the corresponding dihydropyrrolo[3,2-b]quinolones in moderate to excellent yields (38-94%). The generality and substrate scope of this reaction are explored and a possible mechanism is proposed. The results imply that electron-withdrawing groups on N2 of tetrahydro-γ-carbolines and N5-H are necessary. The synthesis of 5 or 7-substituted pyrrolo[3,2-b]quinolones in near quantitative yields was also achieved through deprotection and aromatization of N1-Boc-dihydropyrrolo[3,2-b]quinolones.

  9. Synthesis and Antimicrobial Activity of some Tetrahydro Quinolone Diones and Pyrano[2,3-d]pyrimidine Derivatives

    Science.gov (United States)

    Shahi, Masoume; Foroughifar, Naser; Mobinikhaledi, Akbar

    2015-01-01

    There has been special interest in the chemistry of quinolone and pyrimidine derivatives due to their diverse biological activities such as anticonvulsant, anti-malarial agents, antibacterial, antiviral, cytostatic, antithelemintic, antigenotoxic, anti-cancer agents. These compounds are also used as targeting delayed-type hypersensivity and anti-convulsant agents. As a part of our research works in the synthesis of pyrimidine derivatives containing biological activities, a series of novel pyrano[2,3-d]pyrimidine derivatives 2 and tetrahydro quinolone dione derivatives 3 were synthesized via reaction of tetrahydrobenzo[b]pyrano derivatives 1 with different reagents in suitable yields. The characterization of these synthesized compounds was established by IR, 1H NMR and 13C NMR spectroscopic data. Furthermore, all compounds were subsequently evaluated for their in-vitro antibacterial activity against three bacteria: Staphylococcus aureus (ATTC-25923), Escherichia Coli (ATTC-25922) and Bacillus anthracic (ATTC-25924). PMID:26330864

  10. A novel synthesis of carbon-labelled quinolone-3-carboxylic acid antibacterials

    Energy Technology Data Exchange (ETDEWEB)

    Carr, R.M.; Sutherland, D.R. (Glaxo Research and Development Ltd., Greenford (United Kingdom). Isotope Chemistry Group)

    1994-10-01

    3-Iodoquinolones were prepared from the corresponding quinolone-3-carboxylic acids by Hunsdiecker-type iododecarboxylation reactions with lead tetraacetate and iodine. Cyanation of the iodo compounds with mixtures of potassium [[sup 13]C]cyanide and copper (1) iodide, gave [3-[sup 13]C]cyanoquinolones which on acidic hydrolysis afforded quinolone-[3-[sup 13]C]carboxylic acids. In this way, nalidixic acid, an immediate precursor of norfloxacin, and quinolone WIN57273 were labelled with carbon-13 in the metabolically stable carboxylic acid fragment. (author).

  11. Rational Design, Synthesis, and Biological Evaluation of Heterocyclic Quinolones Targeting the Respiratory Chain of Mycobacterium tuberculosis.

    Science.gov (United States)

    Hong, W David; Gibbons, Peter D; Leung, Suet C; Amewu, Richard; Stocks, Paul A; Stachulski, Andrew; Horta, Pedro; Cristiano, Maria L S; Shone, Alison E; Moss, Darren; Ardrey, Alison; Sharma, Raman; Warman, Ashley J; Bedingfield, Paul T P; Fisher, Nicholas E; Aljayyoussi, Ghaith; Mead, Sally; Caws, Maxine; Berry, Neil G; Ward, Stephen A; Biagini, Giancarlo A; O'Neill, Paul M; Nixon, Gemma L

    2017-05-11

    A high-throughput screen (HTS) was undertaken against the respiratory chain dehydrogenase component, NADH:menaquinone oxidoreductase (Ndh) of Mycobacterium tuberculosis (Mtb). The 11000 compounds were selected for the HTS based on the known phenothiazine Ndh inhibitors, trifluoperazine and thioridazine. Combined HTS (11000 compounds) and in-house screening of a limited number of quinolones (50 compounds) identified ∼100 hits and four distinct chemotypes, the most promising of which contained the quinolone core. Subsequent Mtb screening of the complete in-house quinolone library (350 compounds) identified a further ∼90 hits across three quinolone subtemplates. Quinolones containing the amine-based side chain were selected as the pharmacophore for further modification, resulting in metabolically stable quinolones effective against multi drug resistant (MDR) Mtb. The lead compound, 42a (MTC420), displays acceptable antituberculosis activity (Mtb IC50 = 525 nM, Mtb Wayne IC50 = 76 nM, and MDR Mtb patient isolates IC50 = 140 nM) and favorable pharmacokinetic and toxicological profiles.

  12. Synthesis of chromone, quinolone, and benzoxazinone sulfonamide nucleosides as conformationally constrained inhibitors of adenylating enzymes required for siderophore biosynthesis.

    Science.gov (United States)

    Engelhart, Curtis A; Aldrich, Courtney C

    2013-08-02

    MbtA catalyzes the first committed step of mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) and is responsible for the incorporation of salicylic acid into the mycobactin siderophores. 5'-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS) is an extremely potent nucleoside inhibitor of MbtA that possesses excellent activity against whole-cell Mtb but suffers from poor bioavailability. In an effort to improve the bioavailability, we have designed four conformationally constrained analogues of Sal-AMS that remove two rotatable bonds and the ionized sulfamate group on the basis of computational and structural studies. Herein we describe the synthesis, biochemical, and microbiological evaluation of chromone-, quinolone-, and benzoxazinone-3-sulfonamide derivatives of Sal-AMS. We developed new chemistry to assemble these three heterocycles from common β-ketosulfonamide intermediates. The synthesis of the chromone- and quinolone-3-sulfonamide intermediates features formylation of a β-ketosulfonamide employing dimethylformamide dimethyl acetal to afford an enaminone that can react intramolecularly with a phenol or intermolecularly with a primary amine via addition-elimination reaction(s). The benzoxazinone-3-sulfonamide was prepared by nitrosation of a β-ketosulfonamide followed by intramolecular nucleophilic aromatic substitution. Mitsunobu coupling of these bicyclic sulfonamides with a protected adenosine derivative followed by global deprotection provides a concise synthesis of the respective inhibitors.

  13. Synthesis of quinolones by nickel-catalyzed cycloaddition via elimination of nitrile.

    Science.gov (United States)

    Nakai, Kenichiro; Kurahashi, Takuya; Matsubara, Seijiro

    2013-02-15

    Substituted quinolones were efficiently synthesized via the nickel-catalyzed cycloaddition of o-cyanophenylbenzamide derivatives with alkynes. The reaction involves elimination of a nitrile group by cleavage of the two independent aryl-cyano and aryl-carbonyl C-C bonds of the amides.

  14. Synthesis and biological evaluation of 6-fluoro-3-phenyl-7-piperazinyl quinolone derivatives as potential topoisomerase I inhibitors.

    Science.gov (United States)

    Ge, Raoling; Zhao, Qian; Xie, Zhouling; Lu, Lu; Guo, Qinglong; Li, Zhiyu; Zhao, Li

    2016-10-21

    The design and synthesis of a new series of 6-fluoro-3-phenyl-7-piperazinyl quinolone derivatives, built on the structure of 1-ethyl-3-(6-nitrobenzoxazol-2-yl)-6,8-difluoro-7-(3-methylpiperazin-1-yl)-4(1H)-quinolone, are described. These compounds provide new scaffold for the discovery of Topoisomerase I (Top I) inhibitors and target based assay showed that they can obviously inhibited Top I at 100 μM. The in vitro anti-proliferative activity of these new compounds was evaluated against A549, Hela, BGC-823, and HepG2 cell lines. Compounds 18a-g showed potent inhibitory activity against the growth of those cancer cell lines. The most positive compounds 18f and 18g demonstrated as potent as camptothecin in Top I inhibition assay and MTT assay. Compounds 18f and 18g led to an obvious increase in the percentage of S phase of the cells in 24 h. The in vivo data showed that 18f and 18g inhibited tumor growth with the inhibitory rate of 29.25% and 42.75% at 20 mg/kg, respectively. The data suggested the therapeutic potential for further development.

  15. Design, synthesis and biological characterization of a new class of osteogenic (1H)-quinolone derivatives.

    Science.gov (United States)

    Manetti, Fabrizio; Petricci, Elena; Gabrielli, Annalisa; Mann, Andrè; Faure, Hélène; Gorojankina, Tatiana; Brasseur, Laurent; Hoch, Lucile; Ruat, Martial; Taddei, Maurizio

    2016-10-04

    Smoothened (Smo) is the signal transducer of the Hedgehog (Hh) pathway and its stimulation is considered a potential powerful tool in regenerative medicine to treat severe tissue injuries. Starting from GSA-10, a recently reported Hh activator acting on Smo, we have designed and synthesized a new class of quinolone-based compounds. Modification and decoration of three different portions of the original scaffold led to compounds able to induce differentiation of multipotent mesenchymal cells into osteoblasts. The submicromolar activity of several of these new quinolones (0.4-0.9 μM) is comparable to or better than that of SAG and purmorphamine, two reference Smo agonists. Structure-activity relationships allow identification of several molecular determinants important for the activity of these compounds.

  16. Design, synthesis and antitumor activity of 3-substituted quinolone derivatives (Ⅰ)

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A series of quinolone derivatives containing benzimidazole, benzoxazole or benzothiazole ring were synthesized. The cytotoxicity of 12 new compounds was evaluated in KB, Be17402, A2780 and HT-29 cell lines. Most of synthesized compounds showed moderate inhibitory activity against cancer cells. The inhibitory activities of 6k, against KB and A2780 tumor cells are comparable to that of topotecan, one of topoisomerase I inhibitors.

  17. Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 7. Synthesis and Pharmacological Evaluation of 4-Quinolone-3-carboxamides and 4-Hydroxy-2-quinolone-3-carboxamides as High Affinity Cannabinoid Receptor 2 (CB2R) Ligands with Improved Aqueous Solubility.

    Science.gov (United States)

    Mugnaini, Claudia; Brizzi, Antonella; Ligresti, Alessia; Allarà, Marco; Lamponi, Stefania; Vacondio, Federica; Silva, Claudia; Mor, Marco; Di Marzo, Vincenzo; Corelli, Federico

    2016-02-11

    4-Quinolone-3-carboxamide derivatives have long been recognized as potent and selective cannabinoid type-2 receptor (CB2R) ligands. With the aim to improve their physicochemical properties, basically aqueous solubility, two different approaches were followed, entailing the substitution of the alkyl chain with a basic replacement or scaffold modification to 4-hydroxy-2-quinolone structure. According to the first approach, compound 6d was obtained, showing slightly reduced receptor affinity (K(i) = 60 nM) compared to the lead compound 4 (0.8 nM) but greatly enhanced solubility (400-3400 times depending on the pH of the medium). On the other hand, shifting from 4-quinolone to 4-hydroxy-2-quinolone structure enabled the discovery of a novel class of CB2R ligands, such as 7b and 7c, characterized by K(i) 1300. At pH 7.4, compound 7c resulted by 100-fold more soluble than 4.

  18. Lanthanum triflate triggered synthesis of tetrahydroquinazolinone derivatives of N-allyl quinolone and their biological assessment

    Directory of Open Access Journals (Sweden)

    Jardosh Hardik H.

    2012-01-01

    Full Text Available A series of 24 derivatives of tetrahydroquinazolinone has been synthesized by one-pot cyclocondensation reaction of N-allyl quinolones, cyclic β-diketones and (thiourea/N-phenylthiourea in presence of lanthanum triflate catalyst. This methodology allowed us to achieve the products in excellent yield by stirring at room temperature. All the synthesized compounds were investigated against a representative panel of pathogenic strains using broth microdilution MIC (minimum inhibitory concentration method for their in vitro antimicrobial activity. Amongst these sets of heterocyclic compounds 5h, 6b, 6h, 5f, 5l, 5n and 6g found to have admirable activity.

  19. Synthesis of Some 4-Quinolones and Related Structures for Evaluation as Potential Antimalarial Agents

    Science.gov (United States)

    1974-11-30

    evaluation new com- pounds related to either endochin (2-methyl-3-heptyl-7-.nethoxy-4(lH)- quino - lone) or the 3-carbomethoxy-4(lH)-quinolones that had shown...of aliphatic aldehydes with 2-methyl-4(lH)- quino - lones to give the 3(1-alkenyl) derivatives proved its generality, since it pro- ceeds when both...yields. Tnis facile reaction indicates, once more, the activated nature of the 3 position in the ’(lDOi- quino - lone ring system. 0 0 + CH20 ) CCHYN(CH3

  20. Synthesis, alkaline phosphatase inhibition studies and molecular docking of novel derivatives of 4-quinolones.

    Science.gov (United States)

    Miliutina, Mariia; Ejaz, Syeda Abida; Khan, Shafi Ullah; Iaroshenko, Viktor O; Villinger, Alexander; Iqbal, Jamshed; Langer, Peter

    2017-01-27

    New and convenient methods for the functionalization of the 4-quinolone scaffold at positions C-1, C-3 and C-6 were developed. The 4-quinolone derivatives were evaluated for their inhibitory potential on alkaline phosphatase isozymes. Most of the compounds exhibit excellent inhibitory activity and moderate selectivity. The IC50 values on tissue non-specific alkaline phosphatase (TNAP) were in the range of 1.34 ± 0.11 to 44.80 ± 2.34 μM, while the values on intestinal alkaline phosphatase (IAP) were in the range of 1.06 ± 0.32 to 192.10 ± 3.78 μM. The most active derivative exhibits a potent inhibition on IAP with a ≈14 fold higher selectivity as compared to TNAP. Furthermore, molecular docking calculations were performed for the most potent inhibitors to show their binding interactions within the active site of the respective enzymes.

  1. Metal complexes of the fourth generation quinolone antimicrobial drug gatifloxacin: Synthesis, structure and biological evaluation

    Science.gov (United States)

    Sadeek, Sadeek A.; El-Shwiniy, Walaa H.

    2010-08-01

    Three metal complexes of the fourth generation quinolone antimicrobial agent gatifloxacin (GFLX) with Y(ΙΙΙ), Zr(ΙV) and U(VΙ) have been prepared and characterized with physicochemical and spectroscopic techniques. In these complexes, gatifloxacin acts as a bidentate deprotonated ligand bound to the metal through the ketone oxygen and a carboxylato oxygen. The complexes are six-coordinated with distorted octahedral geometry. The kinetic parameters for gatifloxacin and the three prepared complexes have been evaluated from TGA curves by using Coats-Redfern (CR) and Horowitz-Metzeger (HM) methods. The calculated bond length and force constant, F(U dbnd O), for the UO 2 bond in uranyl complex are 1.7522 Å and 639.46 N m -1. The antimicrobial activity of the complexes has been tested against microorganisms, three bacterial species, such as Staphylococcus aureus ( S. aureus), Escherichia coli ( E. coli) and Pseudomonas aeruginosa ( P. aeruginosa) and two fungi species, penicillium ( P. rotatum) and trichoderma ( T. sp.), showing that they exhibit higher activity than free ligand.

  2. 2beta-Substituted analogues of 4'-iodococaine: synthesis and dopamine transporter binding potencies.

    Science.gov (United States)

    Avor, K S; Singh, S; Seale, T W; Pouw, B; Basmadjian, G P

    1998-06-18

    A series of 2beta-substituted analogues of 4'-iodococaine (3) was synthesized and evaluated in an in vitro dopamine transporter (DAT) binding assay. Selective hydrolysis at the 2beta-position of 3 gave the carboxylic acid 15 that served as the intermediate for the synthesis of compounds 4, 5, and 6-11. The 2beta-alkyl derivatives were obtained from ecgonine methyl ester (17) through a series of reactions leading to the aldehyde 20. Wittig reaction of 20 with methyltriphenylphosphorane followed by hydrogenation and benzoylation gave the products 12 and 13. The binding affinity of 4'-iodococaine (3) was 10-fold less than that of cocaine. The hydroxymethane, acetate, amide, benzyl ester, oxidazole, and ethane derivatives of 3 exhibited decreased binding while the vinyl, phenyl, and ethyl esters showed a moderate increase in binding affinity. Only the isopropyl derivative 8 exhibited a 2-fold increase in binding affinity compared with 4'-iodococaine (3). Hydroxylation of 8 at the 2'-position gave 14 which enhanced not only the binding potency at the DAT by another 2-fold but also the selectivity at the DAT over the norepinephrine and serotonin transporters. Compound 14 failed to stimulate locomotor activity in C57BL/6J mice over a wide dose range and blocked cocaine-induced locomotor stimulant action.

  3. Quinolone pharmacokinetics.

    Science.gov (United States)

    Robson, R A

    1992-12-01

    Fluoroquinolones have broad antibacterial spectra and are active against most Gram-negative and many Gram-positive species. They exhibit excellent oral bioavailability, extensive tissue penetration, low protein binding, and a long elimination half-life. This review compares and contrasts the pharmakonetics of some quinolone antibiotics - especially pefloxacin, ciprofloxacin, enoxacin, norfloxacin, ofloxacin, fleroxacin and lomefloxacin - in terms of their adsorption, distribution, metabolism, elimination, and interactions with other drugs and with food. In addition, the pharmacokinetics of these agents in the elderly and in patients with renal or hepatic impairment is discussed. The fluoroquinolones are established as a major class of antibiotics in the treatment of infections but pharmacokinetics factors should be considered when deciding on the most appropriate of these agents to use in individual patients.

  4. [Quinolones. Nowadays perspectives and mechanisms of resistance].

    Science.gov (United States)

    Álvarez-Hernández, Diego Abelardo; Garza-Mayén, Gilda Sofía; Vázquez-López, Rosalno

    2015-10-01

    Quinolones are a family of synthetic broad-spectrum antimicrobial drugs whose target is the synthesis of DNA. They directly inhibit DNA replication by interacting with two enzymes; DNA gyrase and topoisomerase IV. They have been widely used for the treatment of several community and hospital acquired infections, in the food processing industry and in the agricultural field, making the increasing incidence of quinolone resistance a frequent problem associated with constant exposition to diverse microorganisms. Resistance may be achieved by three non-exclusive mechanisms; through chromosomic mutations in the Quinolone Resistance-Determining Regions of DNA gyrase and topoisomerase IV, by reducing the intracytoplasmic concentrations of quinolones actively or passively and by Plasmid-Mediated Quinolones-Resistance genes, [Qnr determinant genes of resistance to quinolones, variant gene of the aminoglycoside acetyltransferase (AAC(6')-Ib-c)] and encoding genes of efflux pumps (qepA and oqxAB)]. The future of quinolones is uncertain, however, meanwhile they continue to be used in an irrational way, increasing resistance to quinolones should remain as an area of primary priority for research.

  5. A Facile Solid Phase Synthesis of 2—Alkylthio—4(1H)—quinolones

    Institute of Scientific and Technical Information of China (English)

    TANG,Jing; WU,Ming-Guang; HUANG,Xian

    2003-01-01

    The resin-bound cyclic malonic acid ester 2 reacted with aryl isothiocyanate and alkyl halides to afford the key intermediate arylthioaminomethylene cyclic malonic ester resin 3.Subsequently,resin 3 proceeded thermal cyclizaiton giving the 2-alkylthio-4(1H)-quinolones in good yields and excellent purties.

  6. The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity

    Directory of Open Access Journals (Sweden)

    Abdul Naeem

    2016-03-01

    Full Text Available Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first became available for clinical consumption in 1962 and was used mainly for urinary tract infections caused by Escherichia coli and other pathogenic Gram-negative bacteria. Recently, significant work has been carried out to synthesize novel quinolone analogues with enhanced activity and potential usage for the treatment of different bacterial diseases. These novel analogues are made by substitution at different sites—the variation at the C-6 and C-8 positions gives more effective drugs. Substitution of a fluorine atom at the C-6 position produces fluroquinolones, which account for a large proportion of the quinolones in clinical use. Among others, substitution of piperazine or methylpiperazine, pyrrolidinyl and piperidinyl rings also yields effective analogues. A total of twenty six analogues are reported in this review. The targets of quinolones are two bacterial enzymes of the class II topoisomerase family, namely gyrase and topoisomerase IV. Quinolones increase the concentration of drug-enzyme-DNA cleavage complexes and convert them into cellular toxins; as a result they are bactericidal. High bioavailability, relative low toxicity and favorable pharmacokinetics have resulted in the clinical success of fluoroquinolones and quinolones. Due to these superior properties, quinolones have been extensively utilized and this increased usage has resulted in some quinolone-resistant bacterial strains. Bacteria become resistant to quinolones by three mechanisms: (1 mutation in the target site (gyrase and/or topoisomerase IV of quinolones; (2 plasmid-mediated resistance; and (3 chromosome-mediated quinolone resistance. In plasmid-mediated resistance, the efflux of quinolones is increased along with a decrease in the interaction of the drug with gyrase (topoisomerase IV. In the case of

  7. The Current Case of Quinolones: Synthetic Approaches and Antibacterial Activity.

    Science.gov (United States)

    Naeem, Abdul; Badshah, Syed Lal; Muska, Mairman; Ahmad, Nasir; Khan, Khalid

    2016-03-28

    Quinolones are broad-spectrum synthetic antibacterial drugs first obtained during the synthesis of chloroquine. Nalidixic acid, the prototype of quinolones, first became available for clinical consumption in 1962 and was used mainly for urinary tract infections caused by Escherichia coli and other pathogenic Gram-negative bacteria. Recently, significant work has been carried out to synthesize novel quinolone analogues with enhanced activity and potential usage for the treatment of different bacterial diseases. These novel analogues are made by substitution at different sites--the variation at the C-6 and C-8 positions gives more effective drugs. Substitution of a fluorine atom at the C-6 position produces fluroquinolones, which account for a large proportion of the quinolones in clinical use. Among others, substitution of piperazine or methylpiperazine, pyrrolidinyl and piperidinyl rings also yields effective analogues. A total of twenty six analogues are reported in this review. The targets of quinolones are two bacterial enzymes of the class II topoisomerase family, namely gyrase and topoisomerase IV. Quinolones increase the concentration of drug-enzyme-DNA cleavage complexes and convert them into cellular toxins; as a result they are bactericidal. High bioavailability, relative low toxicity and favorable pharmacokinetics have resulted in the clinical success of fluoroquinolones and quinolones. Due to these superior properties, quinolones have been extensively utilized and this increased usage has resulted in some quinolone-resistant bacterial strains. Bacteria become resistant to quinolones by three mechanisms: (1) mutation in the target site (gyrase and/or topoisomerase IV) of quinolones; (2) plasmid-mediated resistance; and (3) chromosome-mediated quinolone resistance. In plasmid-mediated resistance, the efflux of quinolones is increased along with a decrease in the interaction of the drug with gyrase (topoisomerase IV). In the case of chromosome

  8. In Vitro Evaluation of CBR-2092, a Novel Rifamycin-Quinolone Hybrid Antibiotic: Studies of the Mode of Action in Staphylococcus aureus▿

    Science.gov (United States)

    Robertson, Gregory T.; Bonventre, Eric J.; Doyle, Timothy B.; Du, Qun; Duncan, Leonard; Morris, Timothy W.; Roche, Eric D.; Yan, Dalai; Lynch, A. Simon

    2008-01-01

    Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections. PMID:18443108

  9. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus.

    Science.gov (United States)

    Robertson, Gregory T; Bonventre, Eric J; Doyle, Timothy B; Du, Qun; Duncan, Leonard; Morris, Timothy W; Roche, Eric D; Yan, Dalai; Lynch, A Simon

    2008-07-01

    Rifamycins have proven efficacy in the treatment of persistent bacterial infections. However, the frequency with which bacteria develop resistance to rifamycin agents restricts their clinical use to antibiotic combination regimens. In a program directed toward the synthesis of rifamycins with a lower propensity to elicit resistance development, a series of compounds were prepared that covalently combine rifamycin and quinolone pharmacophores to form stable hybrid antibacterial agents. We describe mode-of-action studies with Staphylococcus aureus of CBR-2092, a novel hybrid that combines the rifamycin SV and 4H-4-oxo-quinolizine pharmacophores. In biochemical studies, CBR-2092 exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant. Macromolecular biosynthesis studies confirmed that CBR-2092 has rifampin-like effects on RNA synthesis in rifampin-susceptible strains and quinolone-like effects on DNA synthesis in rifampin-resistant strains. Studies of mutant strains that exhibited reduced susceptibility to CBR-2092 further substantiated RNA polymerase as the primary cellular target of CBR-2092, with DNA gyrase and DNA topoisomerase IV being secondary and tertiary targets, respectively, in strains exhibiting preexisting rifampin resistance. In contrast to quinolone comparator agents, no strains with altered susceptibility to CBR-2092 were found to exhibit changes consistent with altered efflux properties. The combined data indicate that CBR-2092 may have potential utility in monotherapy for the treatment of persistent S. aureus infections.

  10. Synthesis, spectral features and biological activity of some novel hetarylazo dyes derived from 8-chloro-4-hydroxyl-2-quinolone

    Science.gov (United States)

    Yahyazadeh, Asieh; Yousefi, Hessamoddin

    2014-01-01

    In this study, 8-chloro-4-hydroxyl-2-quinolone was synthesized from cyclocondensation of corresponding dianilide and subsequently used as a potent coupling component with some diazotized heterocyclic amines. These compounds were characterized by UV-vis, FT-IR, 1H NMR spectroscopic techniques and elemental analysis. Absorption spectra of these dyes were measured in six polar solvents and discussed with respect to the nature of solvents and substituted groups. The effects of acid, base, temperature and concentration on the visible absorption spectra of the dyes were reported. In addition, the antimicrobial activity of the dyes was explored in detail.

  11. Design, synthesis, antibacterial evaluation and docking study of novel 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolone.

    Science.gov (United States)

    Li, Qing; Xing, Junhao; Cheng, Haibo; Wang, Hui; Wang, Jing; Wang, Shuai; Zhou, Jinpei; Zhang, Huibin

    2015-01-01

    A novel series of 2-hydroxy-3-(nitroimidazolyl)-propyl-derived quinolones 6a-o were synthesized and evaluated for their in vitro antibacterial activity. Most of the target compounds exhibited potent activity against Gram-positive strains. Among them, moxifloxacin analog 6n displayed the most potent activity against Gram-positive strains including S. epidermidis (MIC = 0.06 μg/mL), MSSE (MIC = 0.125 μg/mL), MRSE (MIC = 0.03 μg/mL), S. aureus (MIC = 0.125 μg/mL), MSSA (MIC = 0.125 μg/mL), (MIC = 2 μg/mL). Its activity against MRSA was eightfold more potent than reference drug gatifloxacin. Finally, docking study of the target compound 6n revealed that the binding model of quinolone nucleus was similar to that of gatifloxacin and the 2-hydroxy-3-(nitroimidazolyl)-propyl group formed two additional hydrogen bonds.

  12. Novel substituted benzothiophene and thienothiophene carboxanilides and quinolones: synthesis, photochemical synthesis, DNA-binding properties, antitumor evaluation and 3D-derived QSAR analysis.

    Science.gov (United States)

    Aleksić, Maja; Bertoša, Branimir; Nhili, Raja; Uzelac, Lidija; Jarak, Ivana; Depauw, Sabine; David-Cordonnier, Marie-Hélène; Kralj, Marijeta; Tomić, Sanja; Karminski-Zamola, Grace

    2012-06-14

    A series of new N,N-dimethylaminopropyl- and 2-imidazolinyl-substituted derivatives of benzo[b]thienyl- and thieno[2,3-b]thienylcarboxanilides and benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones were prepared. Quinolones were prepared by the reaction of photochemical dehydrohalogenation of corresponding anilides. Carboxanilides and quinolones were tested for the antiproliferative activity. 2-Imidazolinyl-substituted derivatives showed very prominent activity. By use of the experimentally obtained antitumor measurements, 3D-derived QSAR analysis was performed for the set of compounds. Highly predictive 3D-derived QSAR models were obtained, and molecular properties that have the highest impact on antitumor activity were identified. Carboxanilides 6a-c and quinolones 9a-c and 11a were evaluated for DNA binding propensities and topoisomerases I and II inhibition as part of their mechanism of action assessment. The evaluated differences in the mode of action nicely correlate with the results of the 3D-QSAR analysis. Taken together, the results indicate which modifications of the compounds from the series should further improve their anticancer properties.

  13. Facile synthesis and stereochemical investigation of Mannich base derivatives: evaluation of antioxidant property and antituberculostic potency.

    Science.gov (United States)

    Parthiban, Paramasivam; Subalakshmi, Viswalingam; Balasubramanian, Krishnamurthy; Islam, Md Nurul; Choi, Jae Sue; Jeong, Yeon Tae

    2011-04-15

    A mini-library of diversely substituted 2,4-diaryl-3-azabicyco[3.3.1]nonan-9-one O-methyloximes and their N-methyl analogs were synthesized by a non-laborious, modified and an optimized Mannich condensation in good yields. Both the ring N-methylation and oxime O-methylation were employed by various methods; of them, the usage of (t)BuOK was found to be the superior in terms of good yield in short time. Stereochemistry of all the synthesized compounds was unambiguously established by their NMR spectral ((1)H, (13)C, (1)H-(1)H COSY, (1)H-(13)C one and multiple bond COSY and NOESY) as well as single-crystal XRD studies. Irrespective of the nature and position of the substituents, all the synthesized oxime ethers of the bicyclic Mannich bases as well as their N-methyl analogs adopted the twin-chair conformation with equatorial orientations of all the substituents. All the synthesized oxime ethers were evaluated for their antioxidant property by DPPH radical scavenging method. According to the structure-activity correlations, compound 4y was found to be a lead molecule with the IC(50) of 0.187 mg/mL. Thus, the present study exploits the scope of finding more active analogs by further optimization with the incorporation of more electron enriched alkoxy/amino and/or phenolic groups on the heterocycle as well as oxime ether pharmacophore. Most of the synthesized molecules were screened for their antituberculostic potency against Mycobacterium tuberculosis H(37)Rv by zone of inhibition method. Of them, 4w/5d and 4x showed very promising inhibition zones of 21 and 23 mm, respectively, which leads to the optimization of 4x by introducing various substituents on the O-benzyl moiety to enhance the antituberculostic potency.

  14. Potency of individual bile acids to regulate bile acid synthesis and transport genes in primary human hepatocyte cultures.

    Science.gov (United States)

    Liu, Jie; Lu, Hong; Lu, Yuan-Fu; Lei, Xiaohong; Cui, Julia Yue; Ellis, Ewa; Strom, Stephen C; Klaassen, Curtis D

    2014-10-01

    Bile acids (BAs) are known to regulate their own homeostasis, but the potency of individual bile acids is not known. This study examined the effects of cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA) and ursodeoxycholic acid (UDCA) on expression of BA synthesis and transport genes in human primary hepatocyte cultures. Hepatocytes were treated with the individual BAs at 10, 30, and 100μM for 48 h, and RNA was extracted for real-time PCR analysis. For the classic pathway of BA synthesis, BAs except for UDCA markedly suppressed CYP7A1 (70-95%), the rate-limiting enzyme of bile acid synthesis, but only moderately (35%) down-regulated CYP8B1 at a high concentration of 100μM. BAs had minimal effects on mRNA of two enzymes of the alternative pathway of BA synthesis, namely CYP27A1 and CYP7B1. BAs increased the two major target genes of the farnesoid X receptor (FXR), namely the small heterodimer partner (SHP) by fourfold, and markedly induced fibroblast growth factor 19 (FGF19) over 100-fold. The BA uptake transporter Na(+)-taurocholate co-transporting polypeptide was unaffected, whereas the efflux transporter bile salt export pump was increased 15-fold and OSTα/β were increased 10-100-fold by BAs. The expression of the organic anion transporting polypeptide 1B3 (OATP1B3; sixfold), ATP-binding cassette (ABC) transporter G5 (ABCG5; sixfold), multidrug associated protein-2 (MRP2; twofold), and MRP3 (threefold) were also increased, albeit to lesser degrees. In general, CDCA was the most potent and effective BA in regulating these genes important for BA homeostasis, whereas DCA and CA were intermediate, LCA the least, and UDCA ineffective.

  15. Dysglycemia associated with quinolones.

    Science.gov (United States)

    El Ghandour, Sarah; Azar, Sami T

    2015-06-01

    Antimicrobial therapy is well known to be associated with fluctuations of blood glucose levels. This review aims at exploring the association between glycemic fluctuations and antibiotics mainly focusing on quinolones. Quinolones are associated with hypoglycemia and hyperglycemia. Several mechanism are proposed to explain this causality.

  16. Discovery of pyrido[3,4-g]quinazoline derivatives as CMGC family protein kinase inhibitors: Design, synthesis, inhibitory potency and X-ray co-crystal structure.

    Science.gov (United States)

    Esvan, Yannick J; Zeinyeh, Wael; Boibessot, Thibaut; Nauton, Lionel; Théry, Vincent; Knapp, Stefan; Chaikuad, Apirat; Loaëc, Nadège; Meijer, Laurent; Anizon, Fabrice; Giraud, Francis; Moreau, Pascale

    2016-08-08

    The design and synthesis of new pyrido[3,4-g]quinazoline derivatives is described as well as their protein kinase inhibitory potencies toward five CMGC family members (CDK5, CK1, GSK3, CLK1 and DYRK1A). The interest for this original tricyclic heteroaromatic scaffold as modulators of CLK1/DYRK1A activity was validated by nanomolar potencies (compounds 12 and 13). CLK1 co-crystal structures with two inhibitors revealed the binding mode of these compounds within the ATP-binding pocket.

  17. Drug interactions with Bacillus anthracis topoisomerase IV: biochemical basis for quinolone action and resistance.

    Science.gov (United States)

    Aldred, Katie J; McPherson, Sylvia A; Wang, Pengfei; Kerns, Robert J; Graves, David E; Turnbough, Charles L; Osheroff, Neil

    2012-01-10

    Bacillus anthracis, the causative agent of anthrax, is considered a serious threat as a bioweapon. The drugs most commonly used to treat anthrax are quinolones, which act by increasing the levels of DNA cleavage mediated by topoisomerase IV and gyrase. Quinolone resistance most often is associated with specific serine mutations in these enzymes. Therefore, to determine the basis for quinolone action and resistance, we characterized wild-type B. anthracis topoisomerase IV, the GrlA(S81F) and GrlA(S81Y) quinolone-resistant mutants, and the effects of quinolones and a related quinazolinedione on these enzymes. Ser81 is believed to anchor a water-Mg(2+) bridge that coordinates quinolones to the enzyme through the C3/C4 keto acid. Consistent with this hypothesized bridge, ciprofloxacin required increased Mg(2+) concentrations to support DNA cleavage by GrlA(S81F) topoisomerase IV. The three enzymes displayed similar catalytic activities in the absence of drugs. However, the resistance mutations decreased the affinity of topoisomerase IV for ciprofloxacin and other quinolones, diminished quinolone-induced inhibition of DNA religation, and reduced the stability of the enzyme-quinolone-DNA ternary complex. Wild-type DNA cleavage levels were generated by mutant enzymes at high quinolone concentrations, suggesting that increased drug potency could overcome resistance. 8-Methyl-quinazoline-2,4-dione, which lacks the quinolone keto acid (and presumably does not require the water-Mg(2+) bridge to mediate protein interactions), was more potent than quinolones against wild-type topoisomerase IV and was equally efficacious. Moreover, it maintained high potency and efficacy against the mutant enzymes, effectively inhibited DNA religation, and formed stable ternary complexes. Our findings provide an underlying biochemical basis for the ability of quinazolinediones to overcome clinically relevant quinolone resistance mutations in bacterial type II topoisomerases.

  18. Synthesis and in-vitro antibacterial activity of N-piperazinyl quinolone derivatives with 5-chloro-2-thienyl group

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available Background and the purpose of the study: Fluoroquinolones are an important group of antimicrobial agents that are used widely in the treatment of various infectious diseases. The purpose of the present study was to synthesize new N-piperazinyl quinolone derivatives with 5-chloro-2-theinyl group having possible antimicrobial activity. Methods: Reaction of ciprofloxacin (1, norfloxacin (2 and enoxacin (3 with α-bromoketone 10 or α-bromooxime derivatives 11a-c in DMF, in the presence of NaHCO3 at room temperature, afforded corresponding ketones 4a-c or oxime derivatives 5-7(a-c, respectively. Results and major conclusion: The synthesized compounds were tested against a series of Gram-positive and Gram-negative bacteria. The results of MIC tests against both Gram-positive and Gram-negative bacteria revealed that ciprofloxacin derivatives (compounds 4a, 5a, 6a and 7a were more active than norfloxacin and enoxacin analogues. Compound 5a, containing N-[2-(5-chlorothiophen-2-yl-2-hydroxyiminoethyl] residue provided a high in vitro antibacterial activity against Gram-positive bacteria, with MIC of 0.06, 0.125, 0.5 and 0.125 μg/mL against S. aureus, S. epidermidis, E. feacalis and B. subtilis, respectively. Its activity was found to be 4 to 8 times better than reference drug (ciprofloxacin against all Gram-positive bacteria with the exception of E. feacalis.

  19. 1,2-substituted 4-(1H)-quinolones: synthesis, antimalarial and antitrypanosomal activities in vitro.

    Science.gov (United States)

    Wube, Abraham; Hüfner, Antje; Seebacher, Werner; Kaiser, Marcel; Brun, Reto; Bauer, Rudolf; Bucar, Franz

    2014-09-10

    A diverse array of 4-(1H)-quinolone derivatives bearing substituents at positions 1 and 2 were synthesized and evaluated for antiprotozoal activities against Plasmodium falciparum and Trypanosoma brucei rhodesiense, and cytotoxicity against L-6 cells in vitro. Furthermore, selectivity indices were also determined for both parasites. All compounds tested showed antimalarial activity at low micromolar concentrations, with varied degrees of selectivity against L-6 cells. Compound 5a was found to be the most active against P. falciparum, with an IC50 value of 90 nM and good selectivity for the malarial parasite compared to the L-6 cells. Compound 10a, on the other hand, showed a strong antitrypanosomal effect with an IC50 value of 1.25 µM. In this study side chain diversity was explored by varying the side chain length and substitution pattern on the aliphatic group at position-2 and a structure-antiprotozoal activity study revealed that the aromatic ring introduced at C-2 contributed significantly to the antiprotozoal activities.

  20. Green synthesis of silver nanoparticles: characterization and determination of antibacterial potency

    Science.gov (United States)

    Annamalai, Jayshree; Nallamuthu, Thangaraju

    2016-02-01

    Silver ions (Ag+) and its compounds are highly toxic to microorganisms, exhibiting strong biocidal effects on many species of bacteria but have a low toxicity toward animal cells. In the present study, silver nanoparticles (SNPs) were biosynthesized using aqueous extract of Chlorella vulgaris as reducing agent and size of SNPs synthesized ranged between 15 and 47 nm. SNPs were characterized by UV-visible spectroscopy, scanning electron microscopy, transmission electron microscopy, X-ray diffraction and Fourier infrared spectroscopy, and analyzed for its antibacterial property against human pathogens. This approach of SNPs synthesis involving green chemistry process can be considered for the large-scale production of SNPs and in the development of biomedicines.

  1. Antibacterial action of quinolones: from target to network.

    Science.gov (United States)

    Cheng, Guyue; Hao, Haihong; Dai, Menghong; Liu, Zhenli; Yuan, Zonghui

    2013-08-01

    Quinolones are widely used broad-spectrum antibacterials with incomplete elucidated mechanism of action. Here, molecular basis for the antibacterial action of quinolones, from target to network, is fully discussed and updated. Quinolones trap DNA gyrase or topoisomerase IV to form reversible drug-enzyme-DNA cleavage complexes, resulting in bacteriostasis. Cell death arises from chromosome fragmentation in protein synthesis-dependent or -independent pathways according to distinguished quinolone structures. In the former pathway, irreversible oxidative DNA damage caused by reactive oxygen species kills bacteria eventually. Toxin-antitoxin mazEF is triggered as an additional lethal action. Bacteria survive and develop resistance by SOS and other stress responses. Enlarged knowledges of quinolone actions and bacterial response will provide new targets for drug design and approaches to prevent bacterial resistance.

  2. Apigenin as an anti-quinolone-resistance antibiotic.

    Science.gov (United States)

    Morimoto, Yuh; Baba, Tadashi; Sasaki, Takashi; Hiramatsu, Keiichi

    2015-12-01

    We previously reported the first 'reverse antibiotic' (RA), nybomycin (NYB), which showed a unique antimicrobial activity against Staphylococcus aureus strains. NYB specifically suppressed the growth of quinolone-resistant S. aureus strains but was not effective against quinolone-susceptible strains. Although NYB was first reported in 1955, little was known about its unique antimicrobial activity because it was before the synthesis of the first quinolone ('old quinolone'), nalidixic acid, in 1962. Following our re-discovery of NYB, we looked for other RAs among natural substances that act on quinolone-resistant bacteria. Commercially available flavones were screened against S. aureus, including quinolone-resistant strains, and their minimum inhibitory concentrations (MICs) were compared using the microbroth dilution method. Some of the flavones screened showed stronger antimicrobial activity against quinolone-resistant strains than against quinolone-susceptible ones. Amongst them, apigenin (API) was the most potent in its RA activity. DNA cleavage assay showed that API inhibited DNA gyrase harbouring the quinolone resistance mutation gyrA(Ser84Leu) but did not inhibit 'wild-type' DNA gyrase that is sensitive to levofloxacin. An API-susceptible S. aureus strain Mu50 was also selected using agar plates containing 20mg/L API. Whole-genome sequencing of selected mutant strains was performed and frequent back-mutations (reverse mutations) were found among API-resistant strains derived from the API-susceptible S. aureus strains. Here we report that API represents another molecular class of natural antibiotic having RA activity against quinolone-resistant bacteria.

  3. Synthesis of 4-hydroxy-2(1H)-quinolone derived chalcones, pyrazolines and their antimicrobial, in silico antimalarial evaluations.

    Science.gov (United States)

    Sarveswari, S; Vijayakumar, V; Siva, R; Priya, R

    2015-01-01

    A few derivatives of 3-(4,5-dihydro-5-aryl-1-phenyl-1H-pyrazol-3-yl)-4-hydroxyquinolin-2(1H)-ones (5a-j) that are synthesized from 4-hydroxy-3-(3-arylacryloyl)quinolin-2(1H)-ones (4a-j) by microwave-assisted synthesis are screened for their antimicrobial, in silico antimalarial activities. Among the tested compounds 4h and 5d were found to have a potent antimalarial activity than the standards, and the others are found to show considerable antimalarial activity and moderate antimicrobial activity.

  4. Use of antibiotics and about quinolones in veterinary therapy (ro

    Directory of Open Access Journals (Sweden)

    Crina L. Mosneang

    2012-12-01

    Full Text Available In Romania are being done extensively efforts in the veterinarians education to emphasize the importance and the European regulations familiar behavior, relating to veterinary drugs prescribing, the issues of residues, of antibacterial resistance and of judicious use of the veterinary conditionigs. In this respect, the present synthesis presents an overview, a useful and necessary bibliographical remembrance to veterinary practitioner about antibiotics and quinolones in particular. Are summarized: bacterial antagonism, methods for studying the effectiveness of antibiotics, the mode of action of antibiotics, the phenomenon of resistance to antibiotics and toxic secondary phenomena caused by antibiotics, continued by information about quinolone-carbonic acid derivatives (quinolones them action mechanism, classification and presentation of the main representatives, indications and contraindications, etc. Referate is conceived in two parts about antibiotics and about quinolones.

  5. Synthesis, Crystal Structure, Stacking Effect and Antibacterial Studies of a Novel Quaternary Copper (II Complex with Quinolone

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    Longguan Zhu

    2003-02-01

    Full Text Available The structural properties of a new copper (II complex [Cu2(cip2(bpy2(pip]·6H2O (bpy=2,2’-bipyridyl, cip=1-cyclopropyl-6-4-oxo-1,4-dihydroquinoline-3-carboxylic acid, pip= piperazinyl anion, obtained during the synthesis of the copper complex with ciprofloxacin (cpf, has been investigated. The complex crystallizes in the triclinic system, space group P-1. The cell dimensions are: a=6.874(2 Å, b= 10.761(3 Å, c= 17.969(5 Å, α =80.071(6°, β= 85.253(6°, γ=79.109(6°,V=1284.5(6 Å3, and Z=2. The Cu (II ion displays a five-coordinate square pyramidal coordination with two nitrogen donors from bpy, the 4-keto and 3-carboxylate oxygen donors of cip, and the third nitrogen atom of the pip anion occupying the fifth site. There is a stack effect between cip ring and bpy ring from another molecule, where the stacking distance is about 3.5 Å. The results of elemental analysis and FT-IR measurement are also included. Both ligand and complex were assayed against gram-positive and gram-negative bacteria by the doubling dilutions method. The complex shows the same minimal inhibitory concentration (MIC against S. Aureus and E. Coli bacteria as the corresponding ligand.

  6. Characterization of Campylobacter jejuni DNA gyrase as the target of quinolones.

    Science.gov (United States)

    Changkwanyeun, Ruchirada; Usui, Masaru; Kongsoi, Siriporn; Yokoyama, Kazumasa; Kim, Hyun; Suthienkul, Orasa; Changkaew, Kanjana; Nakajima, Chie; Tamura, Yutaka; Suzuki, Yasuhiko

    2015-08-01

    Quinolones have long been used as the first-line treatment for Campylobacter infections. However, an increased resistance to quinolones has raised public health concerns. The development of new quinolone-based antibiotics with high activity is critical for effective, as DNA gyrase, the target of quinolones, is an essential enzyme for bacterial growth in several mechanisms. The evaluation of antibiotic activity against Campylobacter jejuni largely relies on drug susceptibility tests, which require at least 2 days to produce results. Thus, an in vitro method for studying the activity of quinolones against the C. jejuni DNA gyrase is preferred. To identify potent quinolones, we investigated the interaction of C. jejuni DNA gyrase with a number of quinolones using recombinant subunits. The combination of purified subunits exhibited DNA supercoiling activity in an ATP dependent manner. Drug concentrations that inhibit DNA supercoiling by 50% (IC50s) of 10 different quinolones were estimated to range from 0.4 (sitafloxacin) to >100 μg/mL (nalidixic acid). Sitafloxacin showed the highest inhibitory activity, and the analysis of the quinolone structure-activity relationship demonstrated that a fluorine atom at R-6 might play the important role in the inhibitory activity against C. jejuni gyrase. Measured quinolone IC50s correlated well with minimum inhibitory concentrations (R = 0.9943). These suggest that the in vitro supercoiling inhibition assay on purified recombinant C. jejuni DNA gyrase is a useful and predictive technique to monitor the antibacterial potency of quinolones. And furthermore, these data suggested that sitafloxacin might be a good candidate for clinical trials on campylobacteriosis.

  7. Novel hybrids of metronidazole and quinolones: synthesis, bioactive evaluation, cytotoxicity, preliminary antimicrobial mechanism and effect of metal ions on their transportation by human serum albumin.

    Science.gov (United States)

    Cui, Sheng-Feng; Peng, Li-Ping; Zhang, Hui-Zhen; Rasheed, Syed; Vijaya Kumar, Kannekanti; Zhou, Cheng-He

    2014-10-30

    A novel series of hybrids of metronidazole and quinolones as antimicrobial agents were designed and synthesized. Most prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. Furthermore, these highly active metronidazole-quinolone hybrids showed appropriate ranges of pKa, log P and aqueous solubility to pharmacokinetic behaviors and no obvious toxicity to A549 and human hepatocyte LO2 cells. Their competitive interactions with metal ions to HSA revealed that the participation of Mg(2+) ion in compound 7d-HSA association could result in a concentration increase of free compound 7d. Molecular modeling and experimental investigation of compound 7d with DNA suggested that possible antibacterial mechanism might be in relation with multiple binding sites between bioactive molecules and topo IV-DNA complex.

  8. Synthesis and antibacterial evaluation of a new series of N-Alkyl-2-alkynyl/(E)-alkenyl-4-(1H)-quinolones.

    Science.gov (United States)

    Wube, Abraham; Guzman, Juan-David; Hüfner, Antje; Hochfellner, Christina; Blunder, Martina; Bauer, Rudolf; Gibbons, Simon; Bhakta, Sanjib; Bucar, Franz

    2012-07-09

    To gain further insight into the structural requirements of the aliphatic group at position 2 for their antimycobacterial activity, some N-alkyl-4-(1H)-quinolones bearing position 2 alkynyls with various chain length and triple bond positions were prepared and tested for in vitro antibacterial activity against rapidly-growing strains of mycobacteria, the vaccine strain Mycobacterium bovis BCG, and methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and -16. The compounds were also evaluated for inhibition of ATP-dependent MurE ligase of Mycobacterium tuberculosis. The lowest MIC value of 0.5 mg/L (1.2-1.5 µM) was found against M. fortuitum and M. smegmatis. These compounds displayed no or only weak toxicity to the human lung fibroblast cell line MRC-5 at 100 µM concentration. The quinolone derivatives exhibited pronounced activity against the epidemic MRSA strains (EMRSA-15 and -16) with MIC values of 2-128 mg/L (5.3-364.7 µM), and M. bovis BCG with an MIC value of 25 mg/L (66.0-77.4 µM). In addition, the compounds inhibited the MurE ligase of M. tuberculosis with moderate to weak activity showing IC50 values of 200-774 µM. The increased selectivity towards mycobacterial bacilli with reference to MRC-5 cells observed for 2-alkynyl quinolones compared to their corresponding 2-alkenyl analogues serves to highlight the mycobacterial specific effect of the triple bond. Exploration of a terminal bromine atom at the side chain of N-alkyl-2-(E)-alkenyl-4-(1H)-quinolones showed improved antimycobacterial activity whereas a cyclopropyl residue at N-1 was suggested to be detrimental to antibacterial activity.

  9. Photoprocesses in quinolone substituted

    Science.gov (United States)

    Vasilyeva, N. Y.; Vusovich, O. V.

    2002-03-01

    In the present work the analysis of the possible ways of energy degradation of electron excited states of 4-methyl-7- hydxyquinolone-2 (Q) and its protolytic species is presented (Figure 1); a ratio of radiative and nonradiative channels of deactivation of energy of electronic excitation is established; constants of photophysical processes (internal and intercrossing conversion), proceeding after act of absorption of light are designed. Study of exited state intramolecular proton transfer (ESIPT) in quinolones is interesting as a source of information on the relative importance of these processes in the photophysics and photochemistry of such molecular systems.

  10. Design, synthesis, and antioxidant potency of novel alpha-tocopherol analogues in isolated membranes and intact cells.

    Science.gov (United States)

    Palozza, Paola; Simone, Rossella; Picci, Nevio; Buzzoni, Lisa; Ciliberti, Nunzia; Natangelo, Anna; Manfredini, Stefano; Vertuani, Silvia

    2008-04-01

    In this study, we have designed novel chromanyl derivatives that share with alpha-tocopherol a chromanyl head but differ in the lateral chain in: (i) length and saturation (FEBL-45, 50, 70), (ii) position of double bonds in Z or E (FEBL-50 and 53 and their respective 6-chromanyl methyl derivatives FEBL-161 and 162), or (iii) presence of additional antioxidant molecules, such as the catechol compound hydroxytyrosol (FEBL-80) or dopamine (FEBL-82, 95). The efficiency of these compounds in preventing free-radical-induced oxidative stress was investigated in isolated membranes as well as intact cells. The results of this study clearly show that all compounds synthesized were active in: (i) inhibiting AAPH- or tert-BOOH-induced lipid peroxidation in microsomes and (ii) preventing H2O2-induced ROS production, cell damage, and heat-shock protein expression in immortalized RAT-1 fibroblasts. Such effects were dose- and time-dependent. Independent of the kind of pro-oxidant used, differences in the antioxidant potency of these compounds were found in relation to the chemical structure with respect to the natural alpha-tocopherol: (1) The concomitant presence of a chromanyl head and an additional aromatic ring markedly increased the antioxidant potency of the molecule. In particular, FEBL-82 and FEBL-95, resulting from the molecular combination of trolox and dopamine, were much more potent than alpha-tocopherol, alpha-tocotrienol, and the other synthetic compounds. Moreover, they were also more potent than trolox and dopamine, used alone or in combination, suggesting synergistic cooperative interactions in the molecule between chromanyl and catechol moieties. (2) The length of the side chain affected the antioxidant properties of the molecule: FEBL-70, which displays a bulky squalene side chain, was less effective than the natural alpha-tocotrienol and the synthetic FEBL-45 and FEBL-50. (3) The presence of polyunsaturated double bonds in the side chain in the Z configuration

  11. The regioselective iodination of quinolines, quinolones, pyridones, pyridines and uracil.

    Science.gov (United States)

    Dutta, Uttam; Deb, Arghya; Lupton, David W; Maiti, Debabrata

    2015-12-28

    A radical based direct C-H iodination protocol for quinolines, quinolones, pyridones, pyridines, and uracil has been developed. The iodination occurs in a C3 selective manner for quinolines and quinolones. Pyridones and pyridines undergo C3 and C5 iodination, while dimethyl uracil undergoes C5 iodination. Scope of the method was demonstrated through the rapid synthesis of both electron rich as well as electron poor heteroaromatic iodides. The protocol was found to be scalable and general, while a mechanism has been proposed.

  12. Synthesis, characterization of some novel 1,3,4-oxadiazole compounds containing 8-hydroxy quinolone moiety as potential antibacterial and anticancer agents

    Directory of Open Access Journals (Sweden)

    Vinayak Mahadev Adimule

    2014-12-01

    Full Text Available In the present work a series of novel derivatives of 8-hydroxy quinolone substituted 1,3,4-oxadiazole compounds were synthesized by convergent synthetic method and studied for their antibacterial and anticancer properties. The cell lines used for cytotoxic evaluation were HeLa, Caco-2 and MCF7. The synthetic chemistry involved conversion of various substituted aromatic acids into ethyl ester 2a-e. The ethyl ester was converted into corresponding carbohydrazide 3a-e. Carbohydrazides are reacted with chloroacetic acid, phosphorous oxytrichloride and irradiated with microwave in order to obtain the various key intermediates 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole 4a-e. The 2-(chloromethyl-5-(substituted phenyl-1,3,4-oxadiazole was reacted with 8-hydroxy quinolone in presence of sodium hydride and obtained a series of 8-hydroxy quinoline substituted 1,3,4-oxadiazoles 5a-e. Among the synthesised compounds, the cytotoxicity of the compound 5b i.e. 8-{[5-(2,4-dichlorophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline against MCF7 with IC50 of 5.3µM and the compound 5e i.e. 8-{[5-(4-bromophenyl-1,3,4-oxadiazol-2-yl]methoxy}quinoline showed MIC of < 6.25µg/mL against Staphylococcus aureus which is comparable with the known standards. The standards used for cytotoxic evaluation was 5-fluorouracil and for antibacterial was nitrofurazone

  13. Ring-closing metathesis for the synthesis of a highly G-quadruplex selective macrocyclic hexaoxazole having enhanced cytotoxic potency.

    Science.gov (United States)

    Satyanarayana, Mavurapu; Rzuczek, Suzanne G; Lavoie, Edmond J; Pilch, Daniel S; Liu, Angela; Liu, Leroy F; Rice, Joseph E

    2008-07-01

    The synthesis of a 24-membered macrocyclic hexaoxazole via ring-closing metathesis is described. The target compound selectively stabilizes G-quadruplex DNA with no detectable stabilization of duplex DNA. An MTT cytotoxicity assay indicated that this unsaturated macrocyclic hexaoxazole exhibits significant cytotoxicity toward P388, RPMI 8402, and KB3-1 cell lines with IC50 values of 45, 25, and 38 nM, respectively.

  14. Anilides and quinolones with nitrogen-bearing substituents from benzothiophene and thienothiophene series: synthesis, photochemical synthesis, cytostatic evaluation, 3D-derived QSAR analysis and DNA-binding properties.

    Science.gov (United States)

    Aleksić, Maja; Bertoša, Branimir; Nhili, Raja; Depauw, Sabine; Martin-Kleiner, Irena; David-Cordonnier, Marie-Hélène; Tomić, Sanja; Kralj, Marijeta; Karminski-Zamola, Grace

    2014-01-01

    A series of new anilides (2a-c, 4-7, 17a-c, 18) and quinolones (3a-b, 8a-b, 9a-b, 10-15, 19) with nitrogen-bearing substituents from benzo[b]thiophene and thieno[2,3-c]thiophene series are prepared. Benzo[b]thieno[2,3-c]- and thieno[3',2':4,5]thieno[2,3-c]quinolones (3a-b, 8a-b) are synthesized by the reaction of photochemical dehydrohalogenation from corresponding anilides. Anilides and quinolones were tested for the antiproliferative activity. Fused quinolones bearing protonated aminium group, quaternary ammonium group, N-methylated and protonated aminium group, amino and protonated amino group (8a, 9b, 10-12) showed very prominent anticancer activity, whereby the hydrochloride salt of N',N'-dimethylaminopropyl-substituted quinolone (14) was the most active one, having the IC50 concentration at submicromolar range in accordance with previous QSAR predictions. On the other hand, flexible anilides were among the less active. Chemometric analysis of investigated compounds was performed. 3D-derived QSAR analysis identified solubility, metabolitic stability and the possibility of the compound to be ionized at pH 4-8 as molecular properties that are positively correlated with anticancer activity of investigated compounds, while molecular flexibility, polarizability and sum of hydrophobic surface areas were found to be negatively correlated. Anilides 2a-b, 4-7 and quinolones 3a-b, 8a-b, 9b and 10-14 were evaluated for DNA binding propensities and topoisomerases I/II inhibition as part of their mechanism of action. Among the anilides, only compound 7 presented some DNA binding propensity whereas the quinolones 8b, 9b and 10-14 intercalate in the DNA base pairs, compounds 8b, 9b and 14 being the most efficient ones. The strongest DNA intercalators, compounds 8b, 9b and 14, were clearly distinguished from the other compounds according to their molecular descriptors by the PCA and PLS analysis.

  15. The nonantibiotic small molecule cyslabdan enhances the potency of β-lactams against MRSA by inhibiting pentaglycine interpeptide bridge synthesis.

    Directory of Open Access Journals (Sweden)

    Nobuhiro Koyama

    Full Text Available The nonantibiotic small molecule cyslabdan, a labdan-type diterpene produced by Streptomyces sp. K04-0144, markedly potentiated the activity of the β-lactam drug imipenem against methicillin-resistant Staphylococcus aureus (MRSA. To study the mechanism of action of cyslabdan, the proteins that bind to cyslabdan were investigated in an MRSA lysate, which led to the identification of FemA, which is involved in the synthesis of the pentaglycine interpeptide bridge of the peptidoglycan of MRSA. Furthermore, binding assay of cyslabdan to FemB and FemX with the function similar to FemA revealed that cyslabdan had an affinity for FemB but not FemX. In an enzyme-based assay, cyslabdan inhibited FemA activity, where as did not affected FemX and FemB activities. Nonglycyl and monoglycyl murein monomers were accumulated by cyslabdan in the peptidoglycan of MRSA cell walls. These findings indicated that cyslabdan primarily inhibits FemA, thereby suppressing pentaglycine interpeptide bridge synthesis. This protein is a key factor in the determination of β-lactam resistance in MRSA, and our findings provide a new strategy for combating MRSA.

  16. Design, Synthesis and Evaluation of New Marine Alkaloid-Derived Pentacyclic Structures with Anti-Tumoral Potency

    Directory of Open Access Journals (Sweden)

    Sebastien Boucle

    2015-01-01

    Full Text Available This work describes the synthesis and biological evaluation of a new heterocyclic hybrid derived from the ellipticine and the marine alkaloid makaluvamine A. Pyridoquinoxalinedione 12 was obtained in seven steps with 6.5% overall yield. 12 and its intermediates 1–11 were evaluated for their in vitro cytotoxic activity against different cancer cell lines and tested for their inhibitory activity against the human DNA topoisomerase II. The analysis by electrophoresis shows that the pentacycle 12 inhibits the topoisomerase II like doxorubicine at 100 µM. Compound 9 was found to have an interesting profile, having a cytotoxicity of 15, 15, 15 and 10 μM against Caco-2, HCT-116, Pc-3 and NCI cell lines respectively, without any noticeable toxicity against human fibroblast.

  17. Multi-targeting exploration of new 2-aminothiazolyl quinolones: Synthesis, antimicrobial evaluation, interaction with DNA, combination with topoisomerase IV and penetrability into cells.

    Science.gov (United States)

    Cheng, Yu; Avula, Srinivasa Rao; Gao, Wei-Wei; Addla, Dinesh; Tangadanchu, Vijai Kumar Reddy; Zhang, Ling; Lin, Jian-Mei; Zhou, Cheng-He

    2016-11-29

    A series of new potentially multi-targeting antimicrobial 2-aminothiazolyl quinolones were designed, synthesized and characterized by (1)H NMR, (13)C NMR, IR, MS and HRMS spectra. Bioactive assay manifested that some of the prepared compounds showed moderate to good antibacterial and antifungal activities. Noticeably, compound 10f could effectively inhibit the growth of B. typhi and MRSA with MIC values of 1 and 8 μg/mL, respectively. Experimental results revealed that compound 10f was membrane-active and had the ability to rapidly kill the tested strains and effectively prevent the development of bacterial resistance. Moreover, this compound also exhibited low toxicity against L929 cells. Molecular docking indicated that compound 10f could bind with topoisomerase IV-DNA complexes through hydrogen bonds and hydrophobic interactions. Quantum chemical studies were also performed on 10f to understand the structural features essential for activity. The preliminary mechanism research suggested that compound 10f could intercalate into calf thymus DNA to form a steady supramolecular complex which might block DNA replication to exert the powerful bioactivities.

  18. A simple, fast and cost-effective method of synthesis of cupric oxide nanoparticle with promising antibacterial potency: Unraveling the biological and chemical modes of action.

    Science.gov (United States)

    Chakraborty, Ruchira; Sarkar, Raj Kumar; Chatterjee, Arijit Kumar; Manju, Unnikrishnan; Chattopadhyay, Asoke Prasun; Basu, Tarakdas

    2015-04-01

    Gradual attainment of bacterial resistance to antibiotics led us to develop a robust method of synthesis of stable, colloidal cupric oxide nanoparticle of physiological pH with potential antibacterial action. Cu(II) oxide NP was synthesized by reduction-oxidation of CuCl2, using polyvinyl alcohol as stabilizer. Characteristics and antibacterial activity of the particles were investigated by techniques like UV-Vis spectrophotometry, DLS, AFM, TEM, EDS, FTIR, AAS, agar plating, FACS, gel electrophoresis and XPS. The NPs were about 50 nm in size and cubic in shape with two surface plasmon peaks at 266 and 370 nm and had semi-conducting behavior with a band gap of 3.40 and 3.96 eV. About 80% of precursor CuCl2 was converted to NP. The minimum inhibitory and the minimum bactericidal concentrations of CuO-NP were respectively 120 and 160 μg/mL for Escherichia coli and 180 and 195 μg/mL for Staphylococcus aureus in Luria-Bertani medium. In growth media, the NPs got modified by media organics with displacement of the stabilizer PVA molecules. This modified NP (around 240 nm) killed cells by generating ROS, which finally caused membrane lipid per-oxidation and chromosomal DNA degradation in NP-treated cells. Reports indicate that we are among the few who had prepared CuO-NP in colloidal form. The antibacterial potency of our particle in growth media was much promising than other reports. Our findings demonstrated that 'particle-specific' effect, not 'ion-specific' one, was responsible for the NP action. The NP may be used as a sterilizing agent in various bioprocesses and as substituent of antibiotics, after thorough toxicological study. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. [The molecular physiological and genetic mechanisms underlying the superb efficacy of quinolones].

    Science.gov (United States)

    Long, Quan-xin; He, Ying; Xie, Jian-ping

    2012-08-01

    The fluoroquinolones are the most widely used broad-spectrum antibiotics, accounting for 18% of global antibacterial market share. They can kill bacteria rapidly with variety of derivatives available. Different quinolones vary significantly in rate and spectrum of killing, oxygen requirement for metabolism and reliance upon protein synthesis. Further understanding the sophisticated mechanisms of action of this important antibiotic family based on the molecular genetic response of bacteria can facilitate the discovery of better quinolone derivatives. Factors such as SOS response, bacterial toxin-antitoxin system, programmed death, chromosome fragmentation and reactive oxygen have been implicated in the action to some extent. "Two steps characteristic" of quinolones killing is also emphasized, which might inspire future better quinolones modification.

  20. Synthesis, chemical reactivity as Michael acceptors, and biological potency of monocyclic cyanoenones, novel and highly potent anti-inflammatory and cytoprotective agents.

    Science.gov (United States)

    Zheng, Suqing; Santosh Laxmi, Y R; David, Emilie; Dinkova-Kostova, Albena T; Shiavoni, Katherine H; Ren, Yanqing; Zheng, Ying; Trevino, Isaac; Bumeister, Ronald; Ojima, Iwao; Wigley, W Christian; Bliska, James B; Mierke, Dale F; Honda, Tadashi

    2012-05-24

    Novel monocyclic cyanoenones examined to date display unique features regarding chemical reactivity as Michael acceptors and biological potency. Remarkably, in some biological assays, the simple structure is more potent than pentacyclic triterpenoids (e.g., CDDO and bardoxolone methyl) and tricycles (e.g., TBE-31). Among monocyclic cyanoenones, 1 is a highly reactive Michael acceptor with thiol nucleophiles. Furthermore, an important feature of 1 is that its Michael addition is reversible. For the inhibition of NO production, 1 shows the highest potency. Notably, its potency is about three times higher than CDDO, whose methyl ester (bardoxolone methyl) is presently in phase III clinical trials. For the induction of NQO1, 1 also demonstrated the highest potency. These results suggest that the reactivity of these Michael acceptors is closely related to their biological potency. Interestingly, in LPS-stimulated macrophages, 1 causes apoptosis and inhibits secretion of TNF-α and IL-1β with potencies that are higher than those of bardoxolone methyl and TBE-31.

  1. Quinolone resistance: much more than predicted

    Directory of Open Access Journals (Sweden)

    Alvaro eHernandez

    2011-02-01

    Full Text Available Since quinolones are synthetic antibiotics, it was predicted that mutations in target genes would be the only mechanism through which resistance could be acquired, because there will not be quinolone resistance genes in nature. Contrary to this prediction, a variety of elements ranging from efflux pumps, target-protecting proteins and even quinolone-modifying enzymes have been shown to contribute to quinolone resistance. The finding of some of these elements in plasmids indicates that quinolone resistance can be transferable. As a result, there has been a developing interest on the reservoirs for quinolone resistance genes and on the potential risks associated with the use of these antibiotics in non-clinical environments. As a matter of fact, plasmid-encoded, quinolone-resistance qnr genes originated in the chromosome of aquatic bacteria, thus the use of quinolones in fish farming might constitute a risk for the emergence of resistance. Failure to predict the development of quinolone resistance reinforces the need of taking into consideration the wide plasticity of biological systems for future predictions. This plasticity allows pathogens to deal with toxic compounds, including those with a synthetic origin as quinolones.

  2. Novel cyano- and N-isopropylamidino-substituted derivatives of benzo[b]thiophene-2-carboxanilides and benzo[b]thieno[2,3-c]quinolones: synthesis, photochemical synthesis, crystal structure determination, and antitumor evaluation. 2.

    Science.gov (United States)

    Jarak, Ivana; Kralj, Marijeta; Suman, Lidija; Pavlović, Gordana; Dogan, Jasna; Piantanida, Ivo; Zinić, Mladen; Pavelić, Kresimir; Karminski-Zamola, Grace

    2005-04-01

    Derivatives of 3-chlorobenzo[b]thiophene-2-carboxanilides and their "cyclic" analogues benzo[b]thieno[2,3-c]quinolones were synthesized. Spectroscopic study of the interactions of some representatives of "cyclic" derivatives and their "acyclic" precursors with ds-DNA/RNA supported strong intercalative binding of the former and weak nonintercalative binding of the latter group of compounds. All tested compounds showed a certain antiproliferative effect on a series of human tumor cells and on a normal cell line. Among the compounds, those with one amidino-substituent have shown the best effect. The most active benzo[b]thieno[2,3-c]quinolones induced apparent S and G2/M arrests of the cell cycle, which resulted in apoptosis. These results strongly suggest that the compounds may act as topoisimerase "poisons", which is in good agreement with their intercalative mode of binding to ds-DNA/RNA, in contrast to the studied "acyclic"group of derivatives. 6a and 6d showed the best selectivity by inhibiting the growth of tumor cells but not of normal fibroblasts.

  3. Mechanism of quinolone action and resistance.

    Science.gov (United States)

    Aldred, Katie J; Kerns, Robert J; Osheroff, Neil

    2014-03-18

    Quinolones are one of the most commonly prescribed classes of antibacterials in the world and are used to treat a variety of bacterial infections in humans. Because of the wide use (and overuse) of these drugs, the number of quinolone-resistant bacterial strains has been growing steadily since the 1990s. As is the case with other antibacterial agents, the rise in quinolone resistance threatens the clinical utility of this important drug class. Quinolones act by converting their targets, gyrase and topoisomerase IV, into toxic enzymes that fragment the bacterial chromosome. This review describes the development of the quinolones as antibacterials, the structure and function of gyrase and topoisomerase IV, and the mechanistic basis for quinolone action against their enzyme targets. It will then discuss the following three mechanisms that decrease the sensitivity of bacterial cells to quinolones. Target-mediated resistance is the most common and clinically significant form of resistance. It is caused by specific mutations in gyrase and topoisomerase IV that weaken interactions between quinolones and these enzymes. Plasmid-mediated resistance results from extrachromosomal elements that encode proteins that disrupt quinolone-enzyme interactions, alter drug metabolism, or increase quinolone efflux. Chromosome-mediated resistance results from the underexpression of porins or the overexpression of cellular efflux pumps, both of which decrease cellular concentrations of quinolones. Finally, this review will discuss recent advancements in our understanding of how quinolones interact with gyrase and topoisomerase IV and how mutations in these enzymes cause resistance. These last findings suggest approaches to designing new drugs that display improved activity against resistant strains.

  4. In vitro activity of Ozenoxacin against quinolone-susceptible and quinolone-resistant gram-positive bacteria.

    Science.gov (United States)

    López, Y; Tato, M; Espinal, P; Garcia-Alonso, F; Gargallo-Viola, D; Cantón, R; Vila, J

    2013-12-01

    In vitro activity of ozenoxacin, a novel nonfluorinated topical (L. D. Saravolatz and J. Leggett, Clin. Infect. Dis. 37:1210-1215, 2003) quinolone, was compared with the activities of other quinolones against well-characterized quinolone-susceptible and quinolone-resistant Gram-positive bacteria. Ozenoxacin was 3-fold to 321-fold more active than other quinolones. Ozenoxacin could represent a first-in-class nonfluorinated quinolone for the topical treatment of a broad range of dermatological infections.

  5. A "Double-Edged" Scaffold: Antitumor Power within the Antibacterial Quinolone.

    Science.gov (United States)

    Bisacchi, Gregory S; Hale, Michael R

    2016-01-01

    In the late 1980s, reports emerged describing experimental antibacterial quinolones having significant potency against eukaryotic Type II topoisomerases (topo II) and showing cytotoxic activity against tumor cell lines. As a result, several pharmaceutical companies initiated quinolone anticancer programs to explore the potential of this class in comparison to conventional human topo II inhibiting antitumor drugs such as doxorubicin and etoposide. In this review, we present a modern re-evaluation of the anticancer potential of the quinolone class in the context of today's predominantly pathway-based (rather than cytotoxicity-based) oncology drug R&D environment. The quinolone eukaryotic SAR is comprehensively discussed, contrasted with the corresponding prokaryotic data, and merged with recent structural biology information which is now beginning to help explain the basis for that SAR. Quinolone topo II inhibitors appear to be much less susceptible to efflux-mediated resistance, a current limitation of therapy with conventional agents. Recent advances in the biological understanding of human topo II isoforms suggest that significant progress might now be made in overcoming two other treatment-limiting disadvantages of conventional topo II inhibitors, namely cardiotoxicity and drug-induced secondary leukemias. We propose that quinolone class topo II inhibitors could have a useful future therapeutic role due to the continued need for effective topo II drugs in many cancer treatment settings, and due to the recent biological and structural advances which can now provide, for the first time, specific guidance for the design of a new class of inhibitors potentially superior to existing agents.

  6. DRUG-INTERACTIONS WITH QUINOLONE ANTIBACTERIALS

    NARCIS (Netherlands)

    BROUWERS, JRBJ

    1992-01-01

    The quinolone antibacterials are prone to many interactions with other drugs. Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result. Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts,

  7. DRUG-INTERACTIONS WITH QUINOLONE ANTIBACTERIALS

    NARCIS (Netherlands)

    BROUWERS, JRBJ

    1992-01-01

    The quinolone antibacterials are prone to many interactions with other drugs. Quinolone absorption is markedly reduced with antacids containing aluminium, magnesium and/or calcium and therapeutic failure may result. Other metallic ion-containing drugs, such as sucralfate, iron salts, and zinc salts,

  8. [Review and categorization of quinolone antibiotics].

    Science.gov (United States)

    Benes, Jirí

    2005-02-01

    No standard categorization of quinolone antibiotics into generations may be found in either Czech or world literature. The author recommends a categorization into four groups defined according to their spectrum of action and utilization: 1) preparations for the treatment of urinary tract infections; 2) systemically acting quinolones chiefly efficacious against Gram-negative bacteria; 3) so-called respiratory quinolones; and 4) quinolones with a very broad spectrum of action suitable for the treatment of very complicated infections. The author describes the chief characteristics of the most important quinolone antibiotics, including preparations either in their development stage or whose development has been prematurely interrupted because of adverse side-effects. The list includes all preparations that are or were temporarily registered in the Czech Republic.

  9. Evaluation of quinolone antibacterial consumption

    Directory of Open Access Journals (Sweden)

    E. P. Bernaz

    2016-08-01

    Full Text Available Quinolones are broad-spectrum antibiotics that play an important role in the treatment of serious bacterial infections, especially hospital-acquired infections and others in which resistance to older antibacterial classes is suspected and as first-line therapy is recommended. To determine the place, compare and analyze the use of quinolone antibacterial in the most important departments of EMI during 2009 to 2014 and to assess their results for improvement of patients treatment quality was designed this study. In the evaluated period consumption of quinolone antibacterial in EMI recorded a decline from 91 to 46 DDD/1000 or by 49.45%, in IC departaments from 338.6 to 132.07 or by 61%, and vice versa in SSOT departments an increase from 41.28 to 57.59 DDD/1000 or by 31.51%. Medium annual consumption in all institution recorded 63.03 DDD/1000, respectvely 174.90 in IC and 45.10 in SSOT departments. In 2014 IC departments recorded 2439.8 lei per DDD/1000, that was 8.72 times more than cost of 279.9 lei in SSOT departments and 7.51 times than 324.96 lei per DDD/1000 in all EMI. The yearly medium in EMI is around the same with all other international hospitals of 66.13 DDD/1000 and by 27.23% higher than 49.54 DDD/1000 recorded in large acute Australian public hospitals. The obtained results will be an important data for optimization in planning annual hospital necessities and rational antimicrobial prescribing as well as suggest the idea for expansion development and support antimicrobial stewardship initiatives.

  10. Potencies of oral contraceptives.

    Science.gov (United States)

    Edgren, R A; Sturtevant, F M

    1976-08-15

    Oral contraceptives are combinations of estrogens and progestogens or, in the case of the mini-pills, progestogens alone. With specific test procedures in laboratory animals or human subjects, it is possible to assign potency evaluations to the components relative to the progestational, estrogenic, or antiestrogenic activities of the progestogen or to the estrogenic potencies of the estrogenic component. It might even be possible to quantify the synergistic effects of the estrogen on the progestational agent. Unfortunately, however, it is impossible now to amalgamate such assay results into single estimates of the potencies of the combinations (either the combination products per se or the combination tablets of sequential products). For example, an over-all estrogenic potency of a combination preparation would involve the integration of contributions form the estrogen itself plus the estrogenic products of metabolism of the progestogen minus the antagonistic effect of the progestational agent, if any. These factors cannot now be quantified independently, much less merged into a single figure of clinical significance. Further, even if it were possible to produce such an estimate, it is unlikely that the evaluation would be meaningful in relation to any putative side effect or adverse reaction, i.e., the alleged thrombogenic effects of oral contraceptives cannot currently be related directly to any measure of potency that will allow prediction of these clinical conditions from laboratory models. Any evaluation of the potential of a given contraceptive to produce a specific side effect will depend upon data generated with specific regard to that adverse reaction and the individual product in question.

  11. Conjugation between quinolone-susceptible bacteria can generate mutations in the quinolone resistance-determining region, inducing quinolone resistance.

    Science.gov (United States)

    Pitondo-Silva, André; Martins, Vinicius Vicente; Silva, Carolina Fávero da; Stehling, Eliana Guedes

    2015-02-01

    Quinolones are an important group of antibacterial agents that can inhibit DNA gyrase and topoisomerase IV activity. DNA gyrase is responsible for maintaining bacteria in a negatively supercoiled state, being composed of subunits A and B. Topoisomerase IV is a homologue of DNA gyrase and consists of two subunits codified by the parC and parE genes. Mutations in gyrA and gyrB of DNA gyrase may confer resistance to quinolones, and the majority of resistant strains show mutations between positions 67 and 106 of gyrA, a region denoted the quinolone resistance-determining region (QRDR). The most frequent substitutions occur at positions 83 and 87, but little is known about the mechanisms promoting appearance of mutations in the QRDR. The present study proposes that some mutations in the QRDR could be generated as a result of the natural mechanism of conjugation between bacteria in their natural habitat. This event was observed following conjugation in vitro of two different isolates of quinolone-susceptible Pseudomonas aeruginosa, which transferred plasmids of different molecular weights to a recipient strain of Escherichia coli (HB101), also quinolone-susceptible, generating two different transconjugants that presented mutations in DNA gyrase and acquisition of resistance to all quinolones tested.

  12. In Vitro Resistance Development to Nemonoxacin in Streptococcus pneumoniae: A Unique Profile for a Novel Nonfluorinated Quinolone

    Science.gov (United States)

    Roychoudhury, Siddhartha; Makin, Kelly; Twinem, Tracy; Leunk, Robert

    2016-01-01

    Selection of resistant strains in Streptococcus pneumoniae was studied in vitro with nemonoxacin, a novel nonfluorinated quinolone (NFQ), in comparison with quinolone benchmarks, ciprofloxacin, garenoxacin, and gatifloxacin. In stepwise resistance selection studies, a 256-fold loss of potency was observed after three to four steps of exposure to ciprofloxacin or garenoxacin. In contrast, the loss of potency was limited to eightfold after three steps of exposure to nemonoxacin and repeated attempts to isolate highly resistant organisms after four steps of exposure yielded isolates that could not be subcultured in liquid medium. The quinolone resistance-determining regions of the target genes, parC, parE, gyrA, and gyrB, were analyzed through DNA sequencing. Known mutations, especially in the hotspots of parC and gyrA, were selected with exposure to garenoxacin, ciprofloxacin, and gatifloxacin. In contrast, mutations selected with nemonoxacin were limited to GyrA, GyrB, and ParE, sparing ParC, which is known as a key driver of resistance in clinical isolates of S. pneumoniae. This observation is consistent with previous data using other NFQs, which showed no loss of potency due to ParC mutations in clinical isolates. This apparently unique feature of nemonoxacin is potentially attributable to the structural uniqueness of the NFQs, distinguishing them from the fluoroquinolones that are commonly prescribed for infections by S. pneumoniae. PMID:27267788

  13. A class of 3S-2-aminoacyltetrahydro-beta-carboline-3-carboxylic acids: their facile synthesis, inhibition for platelet activation, and high in vivo anti-thrombotic potency.

    Science.gov (United States)

    Liu, Jiawang; Jiang, Xueyun; Zhao, Ming; Zhang, Xiaoyi; Zheng, Meiqing; Peng, Li; Peng, Shiqi

    2010-04-22

    3S-Tetrahydro-beta-carboline-3-carboxylic acid (TCCA) effectively inhibits ADP-induced platelet activation. This paper used TCCA as a lead, modified its 2-position with amino acids, and provided 20 novel 3S-2-aminoacyl-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acids (5a-t). With the in vitro assay, it was demonstrated that this modification diminished the IC(50) values from 701 nM of TCCA to 10 nM of 5a-t. With the in vivo assay, it was demonstrated that this modification reduced the efficacious dose from 5.0 micromol/kg of TCCA to 0.1 micromol/kg of 5a-t. Comparing the Cerius based conformation of them with that of their analogues, the 3-position modified TCCA, it was suggested that the comparatively unfolded conformation was one of the important factors of enhancing the in vivo antithrombotic potency.

  14. Mechanisms of drug resistance: quinolone resistance.

    Science.gov (United States)

    Hooper, David C; Jacoby, George A

    2015-09-01

    Quinolone antimicrobials are synthetic and widely used in clinical medicine. Resistance emerged with clinical use and became common in some bacterial pathogens. Mechanisms of resistance include two categories of mutation and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes, DNA gyrase and DNA topoisomerase IV, are commonly in a localized domain of the GyrA and ParE subunits of the respective enzymes and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include quinolones as well as other antimicrobials, disinfectants, and dyes. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids can confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is due to Qnr proteins that protect the target enzymes from quinolone action, one mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Thus, the bacterial quinolone resistance armamentarium is large.

  15. An efficient catalyst-free synthesis of novel chromeno[4,3-b]quinolones through Michael initiated ring closure (MIRC) reaction with in situ generated 3-(arylmethylene)chroman-2,4-diones

    Indian Academy of Sciences (India)

    SUDESH KUMARI; JITENDER M KHURANA

    2017-08-01

    A catalyst-free multicomponent reaction capable of affording a wide range of eighteen novel chromeno[4,3-b]quinolone derivatives (6a–6r) via one-pot two-step domino protocol, in ethylene glycol is reported. Catalyst-free conditions along with green solvent system make the process eco-friendly as well aseconomical. High yields of the products were obtained in short reaction times by forming three new bonds and one stereocenter in a single operation. The salient features of the present protocol are short reaction times, eco-friendly solvents, high yields and easy work-up procedure.

  16. [Bactericidal activity of sitafloxacin and other new quinolones against antimicrobial resistant Streptococcus pneumoniae].

    Science.gov (United States)

    Kobayashi, Intetsu; Kanayama, Akiko; Hasegawa, Miyuki; Kaneko, Akihiro

    2013-02-01

    We conducted a study assess the bactericidal activity of sitafloxacin (STFX) against Streptococcus pneumoniae isolates recovered from respiratory infections including penicillin-resistant (PRSP) isolates, macrolide resistant isolates possessing mefA and ermB resistance genes and quinolone resistance isolates with mutations in gyrA or gyrA and parC. Each isolate tested was grown in hemosupplemented Mueller-Hinton broth and adjusted to approximately 10(5) CFU/ mL. Isolates were than exposed to a Cmax antimicrobial blood level that would be attained with routine antimicrobial administration and an antimicrobial level that would be expected 4 hours post-Cmax (Cmax 4hr). Bactericidal activity was measured for up to 8 hours. Excluding a subset of S. pneumoniae isolates with mutations in the quinolone resistance determining region (QRDR), all quinolones showed bactericidal activity at Cmax and Cmax 4 hr antimicrobial concentrations for up to 8 hours. Against S. pneumoniae isolates with either gyrA or gyrA and parC mutations, bactericidal activity of STFX was shown for up to 4 to 8 hours following Cmax based on a limit of detection of quinolones tested where adjusted to concentrations corresponding to their MICs, STFX showed the most rapid bactericidal activity against PRSP. This rapid bactericidal activity in PRSP is a key to the effectiveness of STFX. Our findings show that beyond inhibition of bacterial replication by blocking their DNA replication pathway and synthesis of proteins, STFX demonstrated characteristics contributing to greater bactericidal activity compared to GRNX. In conclusion, of the newer quinolones, STFX showed the strongest bactericidal activity against S. pneumoniae isolates with mutations in the QRDR which indicates that it may show the most effective clinical utility among the quinolones in respiratory infections.

  17. Potency of turmeric (Curcuma longa L. extract and curcumin as anti-obesity by inhibiting the cholesterol and triglycerides synthesis in HepG2 cells

    Directory of Open Access Journals (Sweden)

    Iwan Budiman

    2015-05-01

    Full Text Available Background: Adipocytes accumulate triacylglycerol when excessive food consumption. Adipocyte dysfunction plays an important role in the obesity development. People with a body weight 40 % heavier than the average body weight population at risk of death two times greater than the average body weight. The use of anti-obesity drugs have many side effects, so it is necessary to find the anti-obesity drug with low toxicity. This ex vivo study was conducted to determine the activity of C. longa L. extract in inhibiting triglycerides and cholesterol synthesis and lipid droplet formation on HepG2 cells compared to curcumin. Methods: Anti-obesity activity includes reduced formation of lipid droplet in HepG2 cells can be observed using oil red O staining method. The measurement of triglyceride level was performed according to Randox protocol using Randox TR 210 assay kit. Lipolytic activity by measuring cholesterol levels was performed based on Randox CH 200 kits. Results: This study suggested that the extract of C. longa L. and curcumin have potential anti-obesity compounds. C. longa L. extract have higher activity in inhibiting triglycerides and cholesterol synthesis compared to curcumin with inhibition activities 70.43% and 66.38% respectively in the highest concentration. Conclusion: The C. longa extract posses the anti-adipogenesis potential on inhibiting the synthesis of triglycerides and cholesterol and lipid droplet formation in HepG2 cell as anti-obesity parameters better than curcumin. [Int J Res Med Sci 2015; 3(5.000: 1165-1171

  18. The safety of quinolones in pregnancy.

    Science.gov (United States)

    Yefet, Enav; Salim, Raed; Chazan, Bibiana; Akel, Hiba; Romano, Shabtai; Nachum, Zohar

    2014-11-01

    Quinolones and fluoroquinolones are highly efficient antibiotics. However, concerns regarding possible harmful effects have limited their use during pregnancy. Nevertheless, accumulating clinical data suggest that they may be safe during pregnancy. This review aimed to explore the mechanisms of action of the quinolones and fluoroquinolones, which set the stage for concerns regarding possible teratogenic and mutagenic effects; to clarify the clinical dilemmas that brought forth the necessity in reevaluating the use of those medications during pregnancy; and to review the accumulated data regarding their safety during pregnancy in animal models and humans.

  19. Nitroimidazoles, Quinolones and Oxazolidinones as Fluorine Bearing Antitubercular Clinical Candidates.

    Science.gov (United States)

    Patel, Rahul V; Keum, Young-Soo; Park, Se Won

    2015-01-01

    Tuberculosis is a leading killer of lives worldwide and the global curse of multi-drug resistant tuberculosis is attaining really dangerous levels. Synergistic interaction of HIV and TB is the twin epidemics in resource-limited countries as each potentiate progression of the other. The increasing emergence of MDR-TB and XDR-TB place an immense burden for the treatment of TB with currently available drugs. The situation urgently demands for the discovery of new drugs with novel mode of action and differs in structural features in order to overcome resistance appears in conventional TB therapeutics. The present report covers the discovery of three classes of antituberculosis drugs, Nitroimidazoles, Quinolones and Oxazolidinones, undergoing clinical development with fluorine atom in their structures. Highly electronegative fluorine atom plays a signature role in advancing medicinal innovations as it existence in the drug compounds critically influences metabolic stability and lipophilicity thereby delaying its elimination by the body which results into a long term in vivo efficiency of the drug. Presence of fluorine atom(s) in the drug structures described in this report, has been associated with the several fold increase in the overall potency of the compound as demonstrated since the early discoveries. 6 Fluorinated derivatives from these three classes as pretomanid, delamanid, moxifloxacin, gatifloxacin, linezolid and sutezolid have been discussed with their antituberculosis effects, mode of action, chemical synthetic routes and results of clinical studies.

  20. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and

  1. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and veter

  2. Proficiency study for quinolones in egg

    NARCIS (Netherlands)

    Berendsen, B.J.A.; Stolker, A.A.M.

    2008-01-01

    Studie naar het voorkomen van quinolonen in eieren, beschrijving van de testmaterialen, evaluatie van de toegepaste methoden, resultaten en discussieThe aim of this proficiency study was to give laboratories the possibility to evaluate or demonstrate their competence for the analysis of quinolones i

  3. Plasmid mediated quinolone resistance in Enterobacteriaceae

    NARCIS (Netherlands)

    Veldman, K.T.; LS Klinisch Onderzoek Wagenaar

    2014-01-01

    This thesis describes the occurrence of Plasmid Mediated Quinolone Resistance (PMQR) in Salmonella and E. coli from The Netherlands and other European countries. Furthermore, the genetic background of these genes was characterized. Fluoroquinolones are widely used antibiotics in both human and veter

  4. Opioid analgesics: does potency matter?

    Science.gov (United States)

    Passik, Steven D; Webster, Lynn

    2014-01-01

    Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

  5. The Pseudomonas Quinolone Signal (PQS)

    DEFF Research Database (Denmark)

    Sams, Thomas; Baker, Ysobel; Hodgkinson, James

    2015-01-01

    Pseudomonas aeruginosa is an opportunistichuman pathogen that routinely appears near the top ofpublic health threat lists worldwide. P. aeruginosa causes in-fections by secreting a wealth of exceptionally active exo-products, leading to tissue damage. The synthesis of manyof these virulence factors...

  6. [Investigation of plasmid-mediated quinolone resistance genes in quinolone-resistant Escherichia coli and Klebsiella spp. isolates from bloodstream infections].

    Science.gov (United States)

    Buruk, Celal Kurtuluş; Öztel Ocak, Hikmet; Bayramoğlu, Gülçin; Aydın, Faruk

    2016-04-01

    One of the treatment options of Escherichia coli and Klebsiella spp. infections which are the most common opportunistic pathogens of gram-negative sepsis is quinolones. Resistance to quinolones which act by disrupting DNA synthesis has been increasing. Horizontal transfer of plasmid-mediated quinolone resistance (PMQR) genes play an important role in the spread of resistance. The data about the prevalence of PMQR genes in our country is quite limited. The aim of this study was to investigate the presence of known PMQR genes namely qnrA, qnrB, qnrC, qnrS, qnrD, aac(6')-Ib-cr, qepA and oqxAB amongst quinolone-resistant E. coli and Klebsiella spp. strains isolated from blood cultures. One hundred twenty seven E.coli and 66 Klebsiella isolates detected as nalidixic acid- and/or ciprofloxacin-resistant by phenotypical methods, from 193 blood samples of 187 patients admitted to Karadeniz Technical University, Faculty of Medicine, Department of Medical Microbiology, Bacteriology Unit of Patient Service Laboratory between January 2012 to August 2013 were included in the study. The presence of PMQR genes were investigated by polymerase chain reaction (PCR) and for the detection of aac(6')-Ib-cr variants PCR-restriction fragment length polymorphism (PCR-RFLP) method was used. The positive bands were sequenced using the same primers, and aligned with formerly defined resistance gene sequences, and confirmed. In the study, 56.7% (72/127) of E.coli and 19.7% (13/66) of Klebsiella spp. isolates, with a total of 44% (85/193) of all the isolates were found to be phenotypically resistant to quinolones. Of the 13 resistant Klebsiella isolates, 11 were K.pneumoniae, and two were K.oxytoca. Extended-spectrum beta-lactamase (ESBL)-producing isolates showed higher resistance (50/80, 62.5%) to quinolones than the negative ones (35/113, 30.9%). The prevalence of quinolone resistance genes among resistant E. coli and Klebsiella spp. isolates was determined as qnrA, 1.4% and 15.4%; qnrB, 4

  7. Quinolones in the treatment of Salmonella carriers.

    Science.gov (United States)

    Rodríguez-Noriega, E; Andrade-Villanueva, J; Amaya-Tapia, G

    1989-01-01

    Infections caused by Salmonella typhi are commonly followed by a chronic carrier state despite positive clinical and initial bacteriologic responses. The use of primary antibiotics like chloramphenicol, ampicillin, and trimethoprim-sulfamethoxazole has several major drawbacks, including in some instances the failure to prevent the carrier state. The appearance worldwide of strains with multiple resistance to the most commonly used regimens has prompted the search for new forms of therapy. Among the agents studied have been third-generation cephalosporins and quinolones, which are active in vitro against bacterial enteropathogens like S. typhi. Resolution of chronic carriage of S. typhi and other salmonellae is difficult, and regimens commonly fail (including those that combine antibiotic administration with removal of the gallbladder). In addition to being active in vitro against Salmonella species, the newer quinolones adequately penetrate the intestinal lumen, liver, bile, and gallbladder. Initial experience with norfloxacin and ciprofloxacin in oral treatment of the chronic S. typhi carrier state in adults has been promising.

  8. Topoisomerase IV-quinolone interactions are mediated through a water-metal ion bridge: mechanistic basis of quinolone resistance.

    Science.gov (United States)

    Aldred, Katie J; McPherson, Sylvia A; Turnbough, Charles L; Kerns, Robert J; Osheroff, Neil

    2013-04-01

    Although quinolones are the most commonly prescribed antibacterials, their use is threatened by an increasing prevalence of resistance. The most common causes of quinolone resistance are mutations of a specific serine or acidic residue in the A subunit of gyrase or topoisomerase IV. These amino acids are proposed to serve as a critical enzyme-quinolone interaction site by anchoring a water-metal ion bridge that coordinates drug binding. To probe the role of the proposed water-metal ion bridge, we characterized wild-type, GrlA(E85K), GrlA(S81F/E85K), GrlA(E85A), GrlA(S81F/E85A) and GrlA(S81F) Bacillus anthracis topoisomerase IV, their sensitivity to quinolones and related drugs and their use of metal ions. Mutations increased the Mg(2+) concentration required to produce maximal quinolone-induced DNA cleavage and restricted the divalent metal ions that could support quinolone activity. Individual mutation of Ser81 or Glu85 partially disrupted bridge function, whereas simultaneous mutation of both residues abrogated protein-quinolone interactions. Results provide functional evidence for the existence of the water-metal ion bridge, confirm that the serine and glutamic acid residues anchor the bridge, demonstrate that the bridge is the primary conduit for interactions between clinically relevant quinolones and topoisomerase IV and provide a likely mechanism for the most common causes of quinolone resistance.

  9. Plasmid-mediated quinolone resistance in Enterobacteriaceae: a systematic review with a focus on Mediterranean countries.

    Science.gov (United States)

    Yanat, B; Rodríguez-Martínez, J-M; Touati, A

    2017-03-01

    Quinolones are a family of synthetic broad-spectrum antimicrobial drugs. These molecules have been widely prescribed to treat various infectious diseases and have been classified into several generations based on their spectrum of activity. Quinolones inhibit bacterial DNA synthesis by interfering with the action of DNA gyrase and topoisomerase IV. Mutations in the genes encoding these targets are the most common mechanisms of high-level fluoroquinolone resistance. Moreover, three mechanisms for plasmid-mediated quinolone resistance (PMQR) have been discovered since 1998 and include Qnr proteins, the aminoglycoside acetyltransferase AAC(6')-Ib-cr, and plasmid-mediated efflux pumps QepA and OqxAB. Plasmids with these mechanisms often encode additional antimicrobial resistance (extended spectrum beta-lactamases [ESBLs] and plasmidic AmpC [pAmpC] ß-lactamases) and can transfer multidrug resistance. The PMQR determinants are disseminated in Mediterranean countries with prevalence relatively high depending on the sources and the regions, highlighting the necessity of long-term surveillance for the future monitoring of trends in the occurrence of PMQR genes.

  10. Increasing resistance to quinolones: A four-year prospective study of urinary tract infection pathogens

    Directory of Open Access Journals (Sweden)

    Orhiosefe Omigie

    2009-08-01

    Full Text Available Orhiosefe Omigie, Lawrence Okoror, Patience Umolu, Gladys IkuuhDepartment of Microbiology, Ambrose Alli University, Ekpoma, NigeriaAbstract: A four-year prospective study was carried out to determine the incidence and rate of development of resistance by common urinary tract infection (UTI pathogens to quinolone antimicrobial agents. Results show that there is high intrinsic resistance to the quinolones among strains of Pseudomonas aeruginosa (43.4%, Escherichia coli (26.3%, and Proteus spp. (17.1%. Over four years, rising rates of resistance were observed in P. aeruginosa (14.6% increase, Staphylococcus aureus (9.8%, and E. coli (9.7%. The highest potency was exhibited by ciprofloxacin (91.2%, levofloxacin (89.2%, and moxifloxacin (85.1%, while there were high rates of resistance to nalidixic acid (51.7% and pefloxacin (29.0%. Coliforms, particularly E. coli (>45%, remain the most prevalent causative agents of UTI while females within the age range of 20–50 years were most vulnerable to UTI.Keywords: UTI, microorganisms, antibiotics, resistance

  11. New Role of Quinolones in Respiratory Tract Infections

    Directory of Open Access Journals (Sweden)

    Ronald F Grossman

    1998-01-01

    Full Text Available Because of limited activity of the standard quinolones such as ciprofloxacin and ofloxacin against some clinically important organisms including Streptococcus pneumoniae and methicillin-resistant Staphylococcus aureus, new quinolones have been developed. In addition to their improved activity against S pneumoniae, some also demonstrate excellent anaerobic activity. None of the quinolones have a role to play in the treatment of paediatric infections. Quinolones (both older and newer agents have demonstrated equivalent efficacy to standard antimicrobials in the treatment of acute sinusitis. Several groups have suggested that quinolones are excellent agents in the treatment of high risk patients with acute exacerbations of chronic bronchitis. These patients include the elderly, and those with frequent exacerbations, significant comorbid conditions. long duration of chronic bronchitis and major impairment of lung function. There is no evidence to suggest that the newer quinolones will differ from the currently available agents for th is disease. The major advantage of the newer quinolones appears to be in the treatment of patients with community-acquired pneumonia where pneumococcal infection is a real concern. A new parenteral quinolone with pneumococcal activity may replace the standard macrolide/cephalosporin combination that is commonly prescribed. For patients with nosocomial pneumonia, the newer agents are alternative choices, especially among patients with early onset pneumonia (less than five days of hospitalization, but are unlikely to replace ciprofloxacin in the intensive care unit setting because of poor Pseudomonas aeruginosa coverage.

  12. Metal Complexes of Quinolone Antibiotics and Their Applications: An Update

    Directory of Open Access Journals (Sweden)

    Valentina Uivarosi

    2013-09-01

    Full Text Available Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle at the 7-position, and a carbonyl oxygen atom at the 4-position quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.

  13. Metal complexes of quinolone antibiotics and their applications: an update.

    Science.gov (United States)

    Uivarosi, Valentina

    2013-09-11

    Quinolones are synthetic broad-spectrum antibiotics with good oral absorption and excellent bioavailability. Due to the chemical functions found on their nucleus (a carboxylic acid function at the 3-position, and in most cases a basic piperazinyl ring (or another N-heterocycle) at the 7-position, and a carbonyl oxygen atom at the 4-position) quinolones bind metal ions forming complexes in which they can act as bidentate, as unidentate and as bridging ligand, respectively. In the polymeric complexes in solid state, multiple modes of coordination are simultaneously possible. In strongly acidic conditions, quinolone molecules possessing a basic side nucleus are protonated and appear as cations in the ionic complexes. Interaction with metal ions has some important consequences for the solubility, pharmacokinetics and bioavailability of quinolones, and is also involved in the mechanism of action of these bactericidal agents. Many metal complexes with equal or enhanced antimicrobial activity compared to the parent quinolones were obtained. New strategies in the design of metal complexes of quinolones have led to compounds with anticancer activity. Analytical applications of complexation with metal ions were oriented toward two main directions: determination of quinolones based on complexation with metal ions or, reversely, determination of metal ions based on complexation with quinolones.

  14. Regional variations in quinolone use in France and associated factors.

    Science.gov (United States)

    Gallini, A; Taboulet, F; Bourrel, R

    2012-11-01

    The purpose of this study was to investigate geographic variations in the use of quinolones in France and their associated factors. All reimbursement claims of antimicrobials were collected for 90 % of the French population for the year 2007. Dispensed quantities were then converted into defined daily doses (DDD) and adjusted for the age structure of the national population. Correlations between quinolone use and total antimicrobial use and some morbidity and socio-economic factors were studied using Spearman's rank correlation coefficients. On average, 2.05 DDD of quinolones per 1,000 inhabitants per day (DID) were dispensed in 2007 in France, accounting for 10.2 % of the total antimicrobial consumption in adults. A 40 % variation was observed between the regions with the lowest (1.73 DID) and the highest use (2.44 DID). This variation was more important for anti-pneumococcal quinolones than for quinolones directed against urinary tract infections (coefficients of variation: 26 vs. 6 %). Quinolone use was correlated with some regional socio-economic factors (unemployment, growth domestic product, health expenditures) and physician density, but was independent of the total antimicrobial use. After adjustment for age, large variations in quantitative and qualitative quinolone use were observed across French regions, especially for anti-pneumococcal fluoroquinolones. These results, though not controlled for potential epidemics variations, argue in favour of a possible improvement in quinolone prescribing to be achieved in some regions.

  15. "Changes in cartilage of rats after treatment with Quinolone and in Magnesium-deficient diet "

    Directory of Open Access Journals (Sweden)

    Shakibaei M

    2002-07-01

    Full Text Available Ultrastructural changes in immature articular carilage were studied after treatment of 5-weeks-old rats with ofloxacin, a fluoroquinolone, and in magnesium deficiency.We concluded that quinolone-induced arthropathy is probably due to chelation of functionally available magnesium in joint cartilage as magnesium deficiency in joint cartilage could impair chondrocyte-matrix- interaction which is mediated by cation-dependent integrin-receptors of the β1-subfamily. With immuno-histochemical methods using monoclonal and polyclonal antibodies we showed that B1 integrins were expressed in rat joint cartilage. Joint cartilage lesions were detected in ofloxacin-treated and magnesium-deficient rats. Lesions were more pronounced in the quinolone-treated group. Expression of several integrins was reduced in the vicinity of lesions after oral treatment with 2×600 mg ofloxacin/kg body wt for one day. Gross-structural lesions (e.g. cleft formation, unmasked collagen fibres in magnesium deficient rats were very similar but changes in intergrin expression were less pronounced. Alterations observed on the ultrastructural level showed striking similarities in magnesium-deficient rats and in rats treated with single doses of 600 mg ofloxacin per kg body wt.Typical observation were: bundle shaped, electron-dense aggregates on the surface and in the cytoplasm of chondrocytes, detachement of the cell membrance from the matrix and necrotic chondrocytes, reduced synthesis and/or reduced of extracellular matrix and swelling of cell organelles such as mitochondria.The results of this study confirm our previously reported finding that quinolone-induced arthropathy probably is caued by a reduction of functionally available magnesium (ionized Mg2+ in cartilage. Furthermore, they provide a basis for aimed studies with human cartilage samples from quinolone-treated patients which might be available postmortal or after hip replacement surgery

  16. Vibrational spectra study on quinolones antibiotics

    Science.gov (United States)

    Wang, Yu; Yu, Ke; Wang, Sihuan

    2006-09-01

    In order to be able to fully understand and easily identify the quilonoles, we collected IR and Raman spectra of six quinolones, and attempted to assign the attribution of the observed frequencies and their association with specific modes of vibration. According to the structure, the compounds were divided into the groups, and the similarities and differences were further studied by comparing. The result of the study shows that the frequency and intensity are comparable to the corresponding structure. The spectra not only have the commonness but also the individualities.

  17. A molecular analysis of quinolone-resistant Haemophilus influenzae: validation of the mutations in Quinolone Resistance-Determining Regions.

    Science.gov (United States)

    Shoji, Hisashi; Shirakura, Tetsuro; Fukuchi, Kunihiko; Takuma, Takahiro; Hanaki, Hideaki; Tanaka, Kazuo; Niki, Yoshihito

    2014-04-01

    The mechanism of quinolone-resistance is considered to be amino acid mutations in the type II topoisomerase. We validated the genetic mechanisms of quinolone resistance in Haemophilus influenzae. We obtained 29 H. influenzae strains from a nationwide surveillance program in Japan (including 11 quinolone-resistant strains [moxifloxacin: MFLX or levofloxacin MIC ≥2 μg/ml]). We analyzed the sequences of the Quinolone Resistance-Determining Regions (QRDRs) in GyrA, GyrB, ParC and ParE. Furthermore, we induced resistance in susceptible strains by exposing them to quinolone, and investigated the relationship between mutations in the QRDRs and the MICs. Five amino acid substitutions in GyrA (at Ser84 and Asp88) and ParC (at Gly82, Ser84 and Glu88) were found to be closely related to the MICs. The strains with a MFLX MIC of 0.125-1 and 2-4 μg/ml had one and two mutations, respectively. The strains with a MFLX MIC of ≥8 μg/ml had three or more mutations. The strains with induced resistance with MFLX MICs of 0.5-1 and ≥2 μg/ml also had one and two mutations, respectively. We confirmed that these five mutations strongly contribute to quinolone resistance and found that the degree of resistance is related to the number of the mutations. In addition, the three strains of 18 susceptible strains (16.7%) also had a single mutation. These strains may therefore be in the initial stage of quinolone resistance. Currently, the frequency of quinolone-resistant H. influenzae is still low. However, as has occurred with β-lactams, an increase in quinolone use may lead to more quinolone-resistant strains.

  18. Quinolone-containing therapies in the eradication of Helicobacter pylori.

    Science.gov (United States)

    Chuah, Seng-Kee; Tai, Wei-Chen; Lee, Chen-Hsiang; Liang, Chih-Ming; Hu, Tsung-Hui

    2014-01-01

    Fluoroquinolones, especially levofloxacin, are used in the eradication of Helicobacter pylori worldwide. Many consensus guidelines recommend that the second-line rescue therapy for H. pylori eradication consists of a proton pump inhibitor, a quinolone, and amoxicillin as an option. Unfortunately, quinolone is well associated with a risk of developing bacterial resistance. In this paper, we review quinolone-containing H. pylori eradication regimens and the challenges that influence the efficacy of eradication. It is generally suggested that the use of levofloxacin should be confined to "rescue" therapy only, in order to avoid a further rapid increase in the resistance of H. pylori to quinolone. The impact of quinolone-containing H. pylori eradication regimens on public health issues such as tuberculosis treatment must always be taken into account. Exposure to quinolone is relevant to delays in diagnosing tuberculosis and the development of drug resistance. Extending the duration of treatment to 14 days improves eradication rates by >90%. Tailored therapy to detect fluoroquinolone-resistant strains can be done by culture-based and molecular methods to provide better eradication rates. Molecular methods are achieved by using a real-time polymerase chain reaction to detect the presence of a gyrA mutation, which is predictive of treatment failure with quinolones-containing triple therapy.

  19. Microbial transformations of antimicrobial quinolones and related drugs.

    Science.gov (United States)

    Parshikov, Igor A; Sutherland, John B

    2012-12-01

    The quinolones are an important group of synthetic antimicrobial drugs used for treating bacterial diseases of humans and animals. Microorganisms transform antimicrobial quinolones (including fluoroquinolones) and the pharmacologically related naphthyridones, pyranoacridones, and cinnolones to a variety of metabolites. The biotransformation processes involve hydroxylation of methyl groups; hydroxylation of aliphatic and aromatic rings; oxidation of alcohols and amines; reduction of carboxyl groups; removal of methyl, carboxyl, fluoro, and cyano groups; addition of formyl, acetyl, nitrosyl, and cyclopentenone groups; and cleavage of aliphatic and aromatic rings. Most of these reactions greatly reduce or eliminate the antimicrobial activity of the quinolones.

  20. Insight into Prodrugs of Quinolones and Fluoroquinolones.

    Science.gov (United States)

    Sharma, Prabodh Chander; Piplani, Mona; Mittal, Monika; Pahwa, Rakesh

    2016-01-01

    Quinolones and fluoroquinolones are principal weapons against variety of bacterial infections and exert their antibacterial potential by interfering the activities of bacterial enzymes. As these agents are associated with some limitations, an important approach to overcome these major constraints is to prepare covalent derivatives, i.e. prodrugs. Prodrug design has been employed to improve the limitations of these drugs such as less aqueous solubility, poor absorption and distribution, toxicity, disagreeable taste, poor lipophilicity etc and for improving their pharmacological profile. This paper highlights the utility of various prodrug strategies in optimizing the therapeutic index of these antibacterial agents and their recent patents. Some of their prodrugs being utilized at preclinical and clinical levels have also been discussed. Hence, this paper has been prepared to present the significant findings of various research papers that would be helpful in motivating scientific researchers to forward the research in direction of utilization of prodrugs in clinical therapy.

  1. Oxidation of quinolones with peracids (an in situ EPR study).

    Science.gov (United States)

    Staško, Andrej; Milata, Viktor; Barbieriková, Zuzana; Brezová, Vlasta

    2014-01-01

    4-Oxoquinoline derivatives (quinolones) represent heterocyclic compounds with a variety of biological activities, along with interesting chemical reactivity. The quinolone derivatives possessing secondary amino hydrogen at the nitrogen of the enaminone system are oxidized with 3-chloroperbenzoic acid to nitroxide radicals in the primary step while maintaining their 4-pyridone ring. Otherwise, N-methyl substituted quinolones also form nitroxide radicals coupled with the opening of the 4-pyridone ring in a gradual oxidation of the methyl group via the nitrone-nitroxide spin-adduct cycle. This was confirmed in an analogous oxidation using N,N-dimethylaniline as a model compound. N-Ethyl quinolones in contrast to its N-methyl analog form only one nitroxide radical without a further degradation.

  2. Increasing quinolone resistance in Salmonella enterica serotype enteritidis

    DEFF Research Database (Denmark)

    Mølbak, K.; Gerner-Smidt, P.; Wegener, Henrik Caspar

    2002-01-01

    Until recently, Salmonella enterica serotype Enteritidis has remained sensitive to most antibiotics. However, national surveillance data from Denmark show that quinolone resistance in S. Enteritidis has increased from 0.8% in 1995 to 8.5% in 2000. These data support concerns that the current use...... of quinolone in food animals leads to increasing resistance in S. Enteritidis and that action should be taken to limit such use....

  3. Quantitative structure - mesothelioma potency model ...

    Science.gov (United States)

    Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and comprehensive rat intra-pleural (IP) dose characterization data set with a wide variety of EP size, shape, crystallographic, chemical, and bio-durability properties facilitated extensive statistical analyses of 50 rat IP exposure test results for evaluation of alternative dose pleural mesothelioma response models. Utilizing logistic regression, maximum likelihood evaluations of thousands of alternative dose metrics based on hundreds of individual EP dimensional variations within each test sample, four major findings emerged: (1) data for simulations of short-term EP dose changes in vivo (mild acid leaching) provide superior predictions of tumor incidence compared to non-acid leached data; (2) sum of the EP surface areas (ÓSA) from these mildly acid-leached samples provides the optimum holistic dose response model; (3) progressive removal of dose associated with very short and/or thin EPs significantly degrades resultant ÓEP or ÓSA dose-based predictive model fits, as judged by Akaike’s Information Criterion (AIC); and (4) alternative, biologically plausible model adjustments provide evidence for reduced potency of EPs with length/width (aspect) ratios 80 µm. Regar

  4. ANTIOXIDANT POTENCY OF WATER KEFIR

    Directory of Open Access Journals (Sweden)

    Muneer Alsayadi M.S.

    2013-06-01

    Full Text Available Reactive oxygen species (ROS have strong relationship with several diseases. Many fermented foods were reported to be important sources for antioxidant compounds. Antioxidant activity of water kefir never reported in the scientific literature. The objective of this study was to detect and investigate the antioxidant potency of water kefir. Water kefir was prepared by fermentation of sugar solution with kefir grains for 24h. Antioxidant activity of fresh water kefir drink and its extract with (0.125–5 mg/ml was evaluated using 2,2,-diphenyl-1-pricrylhydrozyl (DPPH scavenging method, and inhibition of ascorbate autoxidation and the reducing power of water kefir were determined, Butylated hydroxyanisole (BHA and ascorbic acid were used for comparison. Water kefir demonstrated great ability to DPPH scavenging ranged (9.88-63.17%. And inhibit ascorbate oxidation by (6.08-25.57% increased in consequent with concentration raising. These results prime to conclude that water kefir could be promisor source of natural antioxidants with good potency in health developing.

  5. New cytotoxic quinolone alkaloids from fruits of Evodia rutaecarpa.

    Science.gov (United States)

    Huang, Xin; Li, Wei; Yang, Xiu-Wei

    2012-06-01

    Three new quinolone alkaloids, 1-methyl-2-[7-hydroxy-(E)-9-tridecenyl]-4(1H)-quinolone (1), 1-methyl-2-[(Z)-4-nonenyl]-4(1H)-quinolone (2), 1-methyl-2-[(1E,5Z)-1,5-undecadienyl]-4(1H)-quinolone (3) and one new natural product, 1-methyl-2-[(E)-1-undecenyl]-4(1H)-quinolone (4), were isolated from the dried and nearly ripe fruits of Evodia rutaecarpa (Juss.) Benth., along with thirteen known compounds (5-17). In addition, one new artificial product, 1-methyl-2-[7-carbonyl-(E)-9-tridecenyl]-4(1H)-quinolone (1A) was also obtained. The structures of these compounds were determined by spectroscopic analyses. The cytotoxic activities of all of the compounds against the human cancer cell lines HL-60, N-87, H-460, and Hep G(2) cells were evaluated by MTT assay. The results showed that these alkaloids inhibited cell proliferation with IC(50) values between 14μM and 22μM.

  6. Quinolones: review of psychiatric and neurological adverse reactions.

    Science.gov (United States)

    Tomé, Ana M; Filipe, Augusto

    2011-06-01

    Quinolones are a class of antibacterial agents for the treatment of several infectious diseases (e.g. urinary and respiratory tract infections). They are used worldwide due to their broad spectrum of activity, high bioavailability and good safety profile. The safety profile varies from quinolone to quinolone. The aim of this article was to review the neurological and psychiatric adverse drug reaction (ADR) profile of quinolones, using a literature search strategy designed to identify case reports and case series. A literature search using PubMed/MEDLINE (from inception to 31 October 2010) was performed to identify case reports and case series related to quinolone-associated neurological and psychiatric ADRs. The search was conducted in two phases: the first phase was the literature search and in the second phase relevant articles were identified through review of the references of the selected articles. Relevant articles were defined as articles referring to adverse events/reactions associated with the use of any quinolone. Abstracts referring to animal studies, clinical trials and observational studies were excluded. Identified case reports were analysed by age group, sex, active substances, dosage, concomitant medication, ambulatory or hospital-based event and seriousness, after Medical Dictionary for Regulatory Activities (MedDRA®) coding. From a total of 828 articles, 83 were identified as referring to nervous system and/or psychiatric disorders induced by quinolones. 145 individual case reports were extracted from the 83 articles. 40.7% of the individual case reports belonged to psychiatric disorders only, whereas 46.9% related to neurological disorders only. Eight (5.5%) individual case reports presented both neurological and psychiatric ADRs. Ciprofloxacin, ofloxacin and pefloxacin were the quinolones with more neurological and psychiatric ADRs reported in the literature. Ciprofloxacin has been extensively used worldwide, which may explain the higher number

  7. [Sample preprocessing method for residual quinolones in honey using immunoaffinity resin].

    Science.gov (United States)

    Ihara, Yoshiharu; Kato, Mihoko; Kodaira, Tsukasa; Itoh, Shinji; Terakawa, Mika; Horie, Masakazu; Saito, Koichi; Nakazawa, Hiroyuki

    2009-06-01

    A sample preparation method was developed for determination of quinolones in honey using immunoaffinity resin. For this purpose, an immunoaffinity resin for quinolones was prepared by coupling a quinolone-specific monoclonal antibody to agarose resin. Honey samples diluted with phosphate buffer were reacted with immunoaffinity resin. After the resin was washed, quinolones were eluted with glycine-HCl. Quinolones in the eluate were determined by HPLC with fluorescence detection. No interfering peak was found on the chromatograms of honey samples. The recoveries of quinolones from samples were over 70% at fortification levels of 20 ng/g (for norfloxacin, ciprofloxacin and enrofloxacin) and 10 ng/g (for danofloxacin). The quantification limits of quinolones were 2 ng/g. This sample preprocessing method using immunoaffinity resin was found to be effective and suitable for determining residual quinolones in honey.

  8. A novel antilithiatic protein from Tribulus terrestris having cytoprotective potency.

    Science.gov (United States)

    Aggarwal, Anshu; Tandon, Simran; Singla, Surinder Kumar; Tandon, Chanderdeep

    2012-08-01

    Adhesion of calcium oxalate (CaOx) crystals to kidney cells is a key event in kidney stones associated with marked hyperoxaluria. As the propensity of stone recurrence and persistent side effects are not altered by surgical techniques available, phytotherapeutic agents could be useful as an adjuvant therapy. The present study is aimed at examining the antilithiatic potency of the protein biomolecules of Tribulus terrestris, a plant which is a common constituent of herbal marketed preparations to treat urolithiasis. Various biochemical methods with mass spectrometry were used to purify and characterize the purified protein. The protective potency of the protein was tested on the oxalate induced injury on renal epithelial cell lines (NRK 52E). An antilithiatic protein having molecular weight of ~ 60kDa was purified. This purified protein showed similarities with Carotenoid cleavage dioxygenase 7 (CCD7) of Arabidopsis thaliana after matching peptide mass fingerprints in MASCOT search engine. An EF hand domain was identified in CCD7 by SCAN PROSITE. Presence of an EF hand domain, a characteristic feature of calcium binding proteins and a role in the synthesis of retinol which is transported by retinol binding protein, a protein found in kidney stone matrix; of CCD7 support the role of TTP as an antilithiatic protein. The protective potency of TTP on NRK 52E was quite comparable to the aqueous extract of cystone. Our findings suggest that this purified protein biomolecule from Tribulus terrestris could open new vista in medical management of urolithiasis.

  9. Prevalence and characterisation of quinolone resistance mechanisms in Salmonella spp.

    Science.gov (United States)

    Wasyl, Dariusz; Hoszowski, Andrzej; Zając, Magdalena

    2014-07-16

    The study was focused on characterisation of quinolone resistance mechanisms in Salmonella isolated from animals, food, and feed between 2008 and 2011. Testing of Minimal Inhibitory Concentrations revealed 6.4% of 2680 isolates conferring ciprofloxacin resistance. Simultaneously 37.7% and 40.8% were accounted for, respectively, nalidixic acid and ciprofloxacin Non Wild-Type populations. Amplification and sequencing of quinolone resistance determining region of topoisomerases genes in 44 isolates identified multiple amino-acid substitutions in gyrA at positions Ser83 (N=22; → Leu, → Phe, → Tyr), Asp87 (N=22; → Asn, → Gly, → Tyr) and parC (Thr57Ser, N=23; Ala141Ser, N=1). No relevant mutations were identified in gyrB and parE. Twelve patterns combining one or two substitutions were related to neither serovar nor ciprofloxacin MIC. In 92 isolates suspected for plasmid mediated quinolone resistance two qnr alleles were found: qnrS1 (or qnrS3; N=50) and qnrB19 (or qnrB10; N=24). Additionally, two isolates with chromosomally encoded mechanisms carried qnrS1 and qnrS2. All tested isolates were negative for qnrA, qnrC, qnrD, qepA, aac(6')-Ib-cr. Both chromosomal and plasmid mediated quinolone resistance determinants were found in several Salmonella serovars and Pulsed Field Gel Electrophoresis was used to assess phylogenetic similarity of selected isolates (N=82). Salmonella Newport was found to accumulate quinolone resistance determinants and the serovar was spreading clonally with either variable gyrA mutations, qnrS1/S3, or qnrB10/B19. Alternatively, various determinants are dispersed among related S. Enteritidis isolates. Antimicrobial selection pressure, multiple resistance determinants and scenarios for their acquisition and spread make extremely difficult to combat quinolone resistance.

  10. A facile route to 5-methyl-5H-indeno[1,2-c]quinolones via palladium-catalyzed cyclization of 2-alkynylbromobenzenes with N,N-dimethyl-2-alkynylanilines.

    Science.gov (United States)

    Pan, Xiaolin; Luo, Yong; Kuang, Yunyan; Li, Guangming

    2014-08-21

    A tandem reaction catalyzed by palladium is developed to provide a facile and simple route for the synthesis of 5-methyl-5H-indeno[1,2-c]quinolones, which can introduce diversity and complexity into the products from readily available starting materials. This transformation proceeds well with good functional group tolerance.

  11. Estrogen potency of oral contraceptive pills.

    Science.gov (United States)

    Chihal, H J; Peppler, R D; Dickey, R P

    1975-01-01

    The estrogen potencies of 9 oral contraceptive pills, Enovid-E, Enovid-5, Ovulen, Demulen, Norinyl+80, Norinyl+50, Ovral, Norlestrin 1 mg. and Norlestrin 2.5 mg., were determined by bioassay. Relative estrogen potency was determined by analysis of variance. Enovid-5, the most estrogenic compound, had a potency of 4.88 compared to ethinyl estradiol, 50 mcg. equal 1.00; Ovral, the least estrogenic compound, had a potency of 0.81, a sixfold difference. Estrogen potencies at a fractional dose of 0.00155 correlate with reports of the incidence of minor side effects and thromboembolic disease. The effect of progestins on estrogen potency was purely additive (norgestrel and norethynodrel), purely antagonistic, or additive at low concentrations and antagonistic at high concentrations (norethindrone, norethindrone acetate, and ethynodiol diacetate). These results suggest that pills with a greater margin of safety might be developed by utilizing greater ratios of progestin to estrogen. In addition, differences in relative estrogen potency of oral contraceptive pills may be used as a basis for better clinical selection.

  12. Stability of frozen stock solutions of beta-lactam antibiotics, cephalosporins, tetracyclines and quinolones used in antibiotic residue screening and antibiotic susceptibility testing.

    Science.gov (United States)

    Okerman, Lieve; Van Hende, Johan; De Zutter, Lieven

    2007-03-14

    The stability of frozen stock solutions of antibiotics belonging to three different families was evaluated using an agar diffusion test, with Bacillus subtilis as a test strain. Diameters of inhibition zones were measured at monthly intervals during 6 months, and the decline in active substance was calculated. Penicillin and amoxicillin lost nearly half of their potency, the cephalosporins ceftiofur and cefapirin one quarter, but ampicillin was more stable. The quinolones flumequine, enrofloxacin and marbofloxacin were relatively stable; the loss of activity was less than 10% after 6 months of preservation at -20 degrees C. This was also the case for doxycycline and chlortetracycline, while oxytetracycline and tetracycline lost about 25% of their potency. When used in microbiology, i.e. for residue testing or for determination of minimum inhibitory concentrations, a diminution of activity less than 25% will not be noticed. For these applications, the four tetracyclines and three quinolones tested can be kept for 6 months at -20 degrees C, while the beta-lactam antibiotics should be discarded after 3 months. Standard stock solutions of beta-lactam antibiotics and cephalosporins should preferably be used the same day when they are intended for quantitative residue analysis.

  13. Acute toxicity evaluation for quinolone antibiotics and their chlorination disinfection processes.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Du, Yuguo

    2014-09-01

    Acute toxicity of 21 quinolone antibiotics was monitored using photobacterium Vibrio fischeri assay. The minimum IC20 (inhibitory concentration for 20% luminescence elimination) was obtained at the least 18.86μmol/L for the tested quinolones. A quantitative structure-activity relationship model was established to investigate the possible mechanism for the acute toxicity. The critical physicochemical descriptors, describing σ and π atom electronegativity, implied that the electron transfer might occur between the quinolones and photobacterium V. fischeri. Although the quinolones exhibited limited acute toxicity to photobacterium, toxicity elevation was detected after their chlorination. Hence, chlorination disinfection treatment of quinolone-containing water should be of concerns.

  14. C-6 aryl substituted 4-quinolone-3-carboxylic acids as inhibitors of hepatitis C virus.

    Science.gov (United States)

    Chen, Yue-Lei; Zacharias, Jeana; Vince, Robert; Geraghty, Robert J; Wang, Zhengqiang

    2012-08-01

    Quinolone-3-carboxylic acid represents a highly privileged chemotype in medicinal chemistry and has been extensively explored as antibiotics and antivirals targeting human immunodeficiency virus (HIV) integrase (IN). Herein we describe the synthesis and anti-hepatitis C virus (HCV) profile of a series of C-6 aryl substituted 4-quinlone-3-carboxylic acid analogues. Significant inhibition was observed with a few analogues at low micromolar range against HCV replicon in cell culture and a reduction in replicon RNA was confirmed through an RT-qPCR assay. Interestingly, evaluation of analogues as inhibitors of NS5B in a biochemical assay yielded only modest inhibitory activities, suggesting that a different mechanism of action could operate in cell culture.

  15. Quinolones and non-steroidal anti-inflammatory drugs interacting with copper(II), nickel(II), cobalt(II) and zinc(II): structural features, biological evaluation and perspectives.

    Science.gov (United States)

    Psomas, George; Kessissoglou, Dimitris P

    2013-05-14

    The structural features of copper(II), nickel(II), cobalt(II) and zinc(II) complexes with the antimicrobial drugs quinolones and non-steroidal anti-inflammatory drugs (NSAIDs) as ligands are discussed. The binding properties of these complexes to biomolecules (calf-thymus DNA, bovine or human serum albumin) are presented and evaluated. The biological activity (antimicrobial, antioxidant and antiproliferative) of selected complexes is investigated. Further perspectives concerning the synthesis and the biological activity of novel complexes with quinolones or NSAIDs attractive to synthetic chemists, biochemists and/or biologists are presented.

  16. Antibacterial potency screening of Capparis zeylanica Linn

    Institute of Scientific and Technical Information of China (English)

    Rezaul Haque; Wahedul Islam; Selina Parween

    2016-01-01

    Objective: To conduct the antibacterial potency and minimum inhibitory concentration of extracts (n-hexane, acetone, chloroform and methanol) obtained from the root, leaf and stem of Capparis zeylanica. Methods: The powdered leaf, root and stem samples were Soxhlet extracted sequentially in n-hexane, acetone, chloroform and methanol. Antibacterial potency was evaluated by following the agar diffusion method and amoxicillin disc was used as a control. Results: In vitro antibacterial activity against 12 bacteria was performed with crude extracts. Among them, all the bacteria showed the moderate activity but chloroform and methanolic extracts showed promising antibacterial potency against Staphylococcus aureus, Sarcina lutea, Bacillus megaterium, Bacillus subtilis, Salmonella typhi and Shigella dysenteriae (leaf > root > stem). This activity was evaluated using disc diffusion method with a standard antibiotic, 30 µg/disc of amoxicillin. Conclusions: Strong antibacterial potency of chloroform and methanolic extracts provides new antibacterial compounds.

  17. Synthesis of High Potency Sweetener N-[3-(3-hydroxy-4-methoxyphenyl) propyl]-aspartyl-L-henylalaninel-methylester%超高倍甜味剂N-[3-(3-羟基-4-甲氧基苯基)丙基]-阿斯巴甜的合成研究

    Institute of Scientific and Technical Information of China (English)

    吴美红; 郑建仙

    2009-01-01

    The development of high potency sweetener changes rapidly, sweetener with safety, low cost, high de-gree of sweetness and top properties is the trend in food industry. On the basis of sweet mechanism, by the reaction of aspartame and 3-hydroxy-4-methoxyphenylpropylaldehyde under the catalysis Pd/C, a new sweetener N-[3-(3-hy-droxy-4-methoxyphenyl) propyl]-aspartyl-L-henylalaninel-methylester is synthesized. Because of hydrophobic group added on aspartame derivative, the sweetness is 23 000 times higher than that of cane sugar. Furthermore, the method is simple and available with high yield. The paper summarizes the synthesis method of the important intermediate, 3-hydroxy-4-methoxyphenylpropylaldehyde, with 49.8% yield, which makes the high potency sweetener possible.%开发安全,低成本,高甜度,性质稳定的甜味剂是食品工业的发展方向.文中从甜味机理出发,以3-羟基-4-甲氧基苯丙醛与阿斯巴甜为原料,通过钯碳催化,合成了N-[3-(3-羟基-4-甲氧基苯基)丙基]-阿斯巴甜.其中,由于疏水基团引入,甜度显著提高,约是蔗糖的23 000倍,且合成工艺简单,产率高,为国内高倍甜味剂大型工业化提供了广阔前景.另外,文中还着重论述了重要中间体3-羟基-4-甲氧基苯丙醛制备,得率为49.8%,为开发新产品奠定了基础.

  18. Comparative assay of Vipera ammodytes antivenom potency.

    Science.gov (United States)

    Capitanescu, Cristian; Macovei Oprescu, Anca Monica; Supeanu, Alexandru; Coculescu, Bogdan Ioan; Strambu, Victor; Macovei, Radu Alexandru; Manole, Gheorghe

    2016-12-01

    The finding of the most appropriate way to assess precisely the antivenom efficacy represents one of the major issues for antivenom standardization and success increasing of antivenom therapy. The efficacy of experimental Vipera ammodytes antivenom raised in sheep was determined using in vivo mouse lethality test, respectively, L-aminoacid oxidase, total proteinase and phospholipase A2 antienzymatic effectiveness. The values gained for the antivenom potency depend on the method of measure. So, some of the most toxic venom proteins own phospholipase A2 activity and provide the highest antivenom potency (lowest effective dose) values by antienzymatic assay method. This value is similar with total antiproteolytic antivenom potency value, but almost three times higher than value obtained by L-aminoacid oxidase (low toxic viper venom protein) antienzymatic assay method.

  19. Recent progress in the development of anti-malarial quinolones.

    Science.gov (United States)

    Beteck, Richard M; Smit, Frans J; Haynes, Richard K; N'Da, David D

    2014-08-30

    Available anti-malarial tools have over the ten-year period prior to 2012 dramatically reduced the number of fatalities due to malaria from one million to less than six-hundred and thirty thousand. Although fewer people now die from malaria, emerging resistance to the first-line anti-malarial drugs, namely artemisinins in combination with quinolines and arylmethanols, necessitates the urgent development of new anti-malarial drugs to curb the disease. The quinolones are a promising class of compounds, with some demonstrating potent in vitro activity against the malaria parasite. This review summarizes the progress made in the development of potential anti-malarial quinolones since 2008. The efficacy of these compounds against both asexual blood stages and other stages of the malaria parasite, the nature of putative targets, and a comparison of these properties with anti-malarial drugs currently in clinical use, are discussed.

  20. Antagonism of vitamin C and vitamin E on action of quinolones

    Directory of Open Access Journals (Sweden)

    Julius E. Surdjawidjaja

    2015-12-01

    Full Text Available The quinolone antibiotics are potent drugs for combating infections caused by various bacterial species with satisfactory results and relatively minimal adverse effects. Antioxidant dietary supplements, such as vitamin C (ascorbic acid and vitamin E (a-tocopherol, are occasionally prescribed along with quinolone antibiotics during the course of treatment of an infection. Therefore it is important to understand the effects of these antioxidants on the antibacterial action of quinolone antibiotics.

  1. Quinolone-based drugs against Toxoplasma gondii and Plasmodium spp.

    Science.gov (United States)

    Anquetin, Guillaume; Greiner, Jacques; Vierling, Pierre

    2005-09-01

    Owing to the rapid emergence of multi-resistant strains of Plasmodium spp. (the causative agents of malaria) and the limitations of drugs used against Toxoplasma gondii (an important opportunistic pathogen associated with AIDS and congenital birth defects), the discovery of new therapeutical targets and the development of new drugs are needed. The presence of the prokaryotic-like organelle in apicomplexan parasites (i.e. plastids), which comprise these major human pathogens, may represent a unique target for antibiotics against these protozoa. Quinolones which are known to be highly potent against bacteria were also found to specifically disrupt these parasites. They inhibit DNA replication by interacting with two essential bacterial type II topoisomerases, DNA gyrase and topoisomerase IV. There are some clues that quinolones act on plastids with a similar mechanism of action. After a brief presentation of plasmodium and toxoplasma dedicated to their life cycle, the chemotherapies presently used in clinics to fight against these protozoa and the potential new targets and drugs, we will focus our attention on their plastid which is one of these promising new targets. Then, we will present the various drugs and generations of quinolones, the leading molecules, and their inhibitory effects against these parasites together with their pharmacological properties that have been established from in vitro and in vivo studies. We will also discuss their possible mode of action.

  2. Probing for improved potency and in vivo bioavailability of excitatory amino acid transporter subtype 1 inhibitors UCPH-101 and UCPH-102: Design, synthesis and pharmacological evaluation of substituted 7-biphenyl analogs

    DEFF Research Database (Denmark)

    Erichsen, Mette Norman; Hansen, J; Artacho Ruiz, Jose;

    2014-01-01

    were designed, synthesized and characterized pharmacologically at EAAT1-3 in a [(3)H]-D-aspartate uptake assay. Most notably, the potent EAAT1 inhibition displayed of UCPH-101 and UCPH-102 was retained in analog 1d in which the napht-1-yl group in the 7-position of UCPH-102 has been replaced by an o...... inhibitors UCPH-101 and UCPH-102. In the present study, we set out to improve the solubility properties of these EAAT1 inhibitors with the objective to develop analogs more suited as pharmacological tools for in vivo studies of EAAT1 in terms of their bioavailability. A total of 23 novel UCPH-101/102 analogs......-biphenyl moiety. In contrast, EAAT1 activity was dramatically compromised in analogs 1e and 1f comprising m- and p-biphenyl groups as 7-substituents, respectively. Analog 1d displayed low bioavailability after oral administration in rats, and this problem was addressed by the synthesis of a series of analogs...

  3. DATA MINING POTENCY ESTIMATORS FROM TOXICOLOGICAL DATABASES

    OpenAIRE

    Piegorsch, Walter W.; Simmons, Susan J.; Zeiger, Errol

    2004-01-01

    We discuss use of data mining techniques to study estimators of toxic potency (activity) in toxicological databases. The methods are slight variations on the standard data mining motif, but fit fully within the larger context of knowledge discovery in databases. An example illustrates the general theme of the approach, using results from a U.S. National Toxicology Program Salmonella mutagenicity database.

  4. Plasmid-Mediated Quinolone Resistance (PMQR) Genes and Class 1 Integrons in Quinolone-Resistant Marine Bacteria and Clinical Isolates of Escherichia coli from an Aquacultural Area.

    Science.gov (United States)

    Tomova, Alexandra; Ivanova, Larisa; Buschmann, Alejandro H; Godfrey, Henry P; Cabello, Felipe C

    2017-06-23

    Antimicrobial usage in aquaculture selects for antimicrobial-resistant microorganisms in the marine environment. The relevance of this selection to terrestrial animal and human health is unclear. Quinolone-resistance genes qnrA, qnrB, and qnrS were chromosomally located in four randomly chosen quinolone-resistant marine bacteria isolated from an aquacultural area with heavy quinolone usage. In quinolone-resistant uropathogenic clinical isolates of Escherichia coli from a coastal area bordering the same aquacultural region, qnrA was chromosomally located in two E. coli isolates, while qnrB and qnrS were located in small molecular weight plasmids in two other E. coli isolates. Three quinolone-resistant marine bacteria and three quinolone-resistant E. coli contained class 1 integrons but without physical association with PMQR genes. In both marine bacteria and uropathogenic E. coli, class 1 integrons had similar co-linear structures, identical gene cassettes, and similarities in their flanking regions. In a Marinobacter sp. marine isolate and in one E. coli clinical isolate, sequences immediately upstream of the qnrS gene were homologous to comparable sequences of numerous plasmid-located qnrS genes while downstream sequences were different. The observed commonality of quinolone resistance genes and integrons suggests that aquacultural use of antimicrobials might facilitate horizontal gene transfer between bacteria in diverse ecological locations.

  5. Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves.

    Science.gov (United States)

    Hordijk, Joost; Veldman, Kees; Dierikx, Cindy; van Essen-Zandbergen, Alieda; Wagenaar, Jaap A; Mevius, Dik

    2012-04-23

    Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional data on quinolone resistance mechanisms in non-pathogenic bacteria from healthy veal calves is limited. The purpose of this study was to determine the prevalence and characteristics of quinolone resistance mechanisms in Escherichia coli isolates from veal calves, after more than 20 years of quinolone usage in veal calves. MIC values were determined for all isolates collected as part of a national surveillance program on antimicrobial resistance in commensal bacteria in food-producing animals in The Netherlands. From the strains collected from veal calves in 2007 (n=175) all isolates with ciprofloxacin MIC ≥ 0.125 mg/L (n=25) were selected for this study, and screened for the presence of known quinolone resistance determinants. In this selection only chromosomal mutations in the topoisomerase type II and IV genes were detected. The number of mutations found per isolate correlated with an increasing ciprofloxacin MIC. No plasmid-mediated quinolone resistance genes were found. The contribution of efflux pumps varied from no contribution to a 16-fold increase in susceptibility. No correlation was found with the presence of resistance genes of other antimicrobial classes, even though all quinolone non-wild type isolates were resistant to 3 or more classes of antibiotics other than quinolones. Over twenty years of quinolone usage in veal calves in The Netherlands did not result in a widespread occurrence of plasmid-mediated quinolone resistance, limiting the transmission of quinolone resistance to clonal distribution.

  6. N-Aryl-oxazolidin-2-imine Muscle Selective Androgen Receptor Modulators Enhance Potency through Pharmacophore Reorientation

    Energy Technology Data Exchange (ETDEWEB)

    Nirschl, Alexandra A.; Zou, Yan; Krystek, Jr., Stanley R.; Sutton, James C.; Simpkins, Ligaya M.; Lupisella, John A.; Kuhns, Joyce E.; Seethala, Ramakrishna; Golla, Rajasree; Sleph, Paul G.; Beehler, Blake C.; Grover, Gary J.; Egan, Donald; Fura, Aberra; Vyas, Viral P.; Li, Yi-Xin; Sack, John S.; Kish, Kevin F.; An, Yongmi; Bryson, James A.; Gougoutas, Jack Z.; DiMarco, John; Zahler, Robert; Ostrowski, Jacek; Hamann, Lawrence G.; (BMS)

    2010-11-09

    A novel selective androgen receptor modulator (SARM) scaffold was discovered as a byproduct obtained during synthesis of our earlier series of imidazolidin-2-ones. The resulting oxazolidin-2-imines are among the most potent SARMs known, with many analogues exhibiting sub-nM in vitro potency in binding and functional assays. Despite the potential for hydrolytic instability at gut pH, compounds of the present class showed good oral bioavailability and were highly active in a standard rodent pharmacological model.

  7. Impact of mutations in DNA gyrase genes on quinolone resistance in Campylobacter jejuni.

    Science.gov (United States)

    Changkwanyeun, Ruchirada; Yamaguchi, Tomoyuki; Kongsoi, Siriporn; Changkaew, Kanjana; Yokoyama, Kazumasa; Kim, Hyun; Suthienkul, Orasa; Usui, Masaru; Tamura, Yutaka; Nakajima, Chie; Suzuki, Yasuhiko

    2016-10-01

    Amino acid substitutions providing quinolone resistance to Campyloabcter jejuni have been found in the quinolone resistance-determining region of protein DNA gyrase subunit A (GyrA), with the highest frequency at position 86 followed by position 90. In this study, wild-type and mutant recombinant DNA gyrase subunits were expressed in Escherichia coli and purified using Ni-NTA agarose column chromatography. Soluble 97 kDa GyrA and 87 kDa DNA gyrase subunit B were shown to reconstitute ATP-dependent DNA supercoiling activity. A quinolone-inhibited supercoiling assay demonstrated the roles of Thr86Ile, Thr86Ala, Thr86Lys, Asp90Asn, and Asp90Tyr amino acid substitutions in reducing sensitivity to quinolones. The marked effect of Thr86Ile on all examined quinolones suggested the advantage of this substitution in concordance with recurring isolation of quinolone-resistant C. jejuni. An analysis of the structure-activity relationship showed the importance of the substituent at position 8 in quinolones to overcome the effect of Thr86Ile. Sitafloxacin (SIT), which has a fluorinate cyclopropyl ring at R-1 and a chloride substituent at R-8, a characteristic not found in other quinolones, showed the highest inhibitory activity against all mutant C. jejuni gyrases including ciprofloxacin-resistant mutants. The results suggest SIT as a promising drug for the treatment of campylobacteriosis caused by CIP-resistant C. jejuni. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Contribution of topoisomerase IV mutation to quinolone resistance in Mycoplasma genitalium.

    Science.gov (United States)

    Yamaguchi, Yuko; Takei, Masaya; Kishii, Ryuta; Yasuda, Mitsuru; Deguchi, Takashi

    2013-04-01

    The mechanism of quinolone resistance in Mycoplasma genitalium remains poorly understood due to difficulties with in vitro culture, especially of clinical isolates. In this study, to confirm the association between mutations in topoisomerases and antimicrobial susceptibilities to quinolones, ciprofloxacin-resistant mutant strains were selected using the cultivable type strain ATCC 33530. Sequence analysis revealed that the mutant strains harbored mutations in topoisomerase IV: Gly81Cys in ParC, Pro261Thr in ParC, or Asn466Lys in ParE. The MICs of all quinolones tested against the mutant strains were 2- to 16-fold higher than those against the wild-type strain. No cross-resistance was observed with macrolides or tetracyclines. We determined the inhibitory activities of quinolones against DNA gyrase and topoisomerase IV in order to investigate the correlation between antimicrobial susceptibility and inhibitory activity against the target enzymes, considered the primary targets of quinolones. Furthermore, using enzymatic analysis, we confirmed that Gly81Cys in the ParC quinolone resistance-determining region (QRDR) contributed to quinolone resistance. This is the first study to isolate quinolone-resistant mutant strains of M. genitalium harboring substitutions in the parC or parE gene in vitro and to measure the inhibitory activities against the purified topoisomerases of M. genitalium.

  9. Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations in quinolone-resistant Escherichia coli isolated from humans and swine in Denmark

    DEFF Research Database (Denmark)

    Cavaco, Lina; Frimodt-Møller, Niels; Hasman, Henrik;

    2008-01-01

    Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations (MICs) of nalidixic acid (NAL) and ciprofloxacin (CIP) were investigated in 124 Escherichia coli isolated from humans (n = 85) and swine (n = 39) in Denmark. The collection included 59 high-level CIP......-resistant isolates (MIC >= 4) from human (n = 51) and pig origin (n = 8) and 65 low-level CIP-resistant isolates (MIC >= 0.125) from human (n = 34) and pig origin (n = 31). Resistance by target modification was screened by PCR amplification and sequencing, of the quinolone resistance determining regions (QRDRs......A and qnrS genes conferring quinolone resistance by target protection were detected in two human low-level CIP-resistant isolates that did not display NAL resistance. As expected, target mutation in QRDRs was the most prevalent mechanism of quinolone resistance. This mechanism was complemented by efflux...

  10. 21 CFR 640.56 - Quality control test for potency.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Quality control test for potency. 640.56 Section...) BIOLOGICS ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Cryoprecipitate § 640.56 Quality control test for potency. (a) Quality control tests for potency of antihemophilic factor shall be...

  11. 9 CFR 113.9 - New potency test.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false New potency test. 113.9 Section 113.9 Animals and Animal Products ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES... New potency test. A potency test written into the filed Outline of Production for a product shall be...

  12. THEORETICAL STUDY OF PODOPHYLLOTOXIN AND QUINOLONE ANALOGUES AS ANTITUMOR DRUGS

    Institute of Scientific and Technical Information of China (English)

    何峰; 戴颖仪; 朱孝峰; 黄爱东; 张翎; 颜少平; 刘宗潮

    2002-01-01

    Objective: To study the active sites of podophyllotoxin derivatives. Methods: Some podophyllotoxin derivatives were analyzed by quantum and mechanics method. Results: Some information was given according to the calculation results about HOMO and LUMO electron density. The C-4 position is the position for effective modification. The B ring and E ring are important active centers. Conclusion: The hole of positive charge in B ring easily combines with an acceptor within the molecular. Some quinolones with similar electronic construction to podophyllotoxin may have antitumor activity.

  13. Thermodynamic study by infrared spectroscopy of the association of 2-quinolone, some carboxylic acids, and the corresponding 2-quinolone--acid mixed dimers

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, J.C.

    1971-01-01

    Self-association of 2-quinolone in carbon tetrachloride was studied by infrared spectroscopy, using the absorption bands in the amide NH and carbonyl stretching regions. 2-Quinolone forms a cyclic dimer from which the enthalpy (..delta..H/sup 0/, kcal/mol), free energy (..delta..G/sup 0//sub 22/, kcal/mol), and entropy (..delta..S/sup 0/, eu) of association are -8.69, -6.11, and -8.76, respectively. Dimer formation is via a carbonyl-hydrogen bond, although evidence exists for the formation of a small amount of dimer via a ..pi..-hydrogen bond. 2-Quinolone was also found to form cyclic mixed dimers with carboxylic acids. Mixed dimers of 2-quinolone with benzoic, cyclohexanecarboxylic, and 4-cyclohexylbutanoic acids gave ..delta..H/sup 0/ values of -12.2, -10.3, and -10.4; ..delta..G/sup 0//sub 22/ values of -6.36, -5.94, and -5.78; and ..delta..S/sup 0/ values of -19.9, -14.8, and -15.6, respectively. Thermodynamic data on the acid dimers and spectral data on the different systems studied are also reported. The 2-quinolone-carboxylic acid interaction is of importance because of the simultaneous occurrence of quinolones and carboxylic acids in many biologically derived materials.

  14. Comparative in vitro activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, and other quinolones against clinical isolates.

    Science.gov (United States)

    Lauderdale, Tsai-Ling; Shiau, Yih-Ru; Lai, Jui-Fen; Chen, Hua-Chien; King, Chi-Hsin R

    2010-03-01

    The in vitro antibacterial activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, against 770 clinical isolates were investigated. Nemonoxacin (tested as its malate salt, TG-875649) showed better in vitro activity than ciprofloxacin and levofloxacin against different species of staphylococci, streptococci, and enterococci, Neisseria gonorrhoeae, and Haemophilus influenzae. The in vitro activity of TG-875649 was also comparable to or better than that of moxifloxacin against these pathogens, which included ciprofloxacin-resistant, methicillin-resistant Staphylococcus aureus and levofloxacin-resistant Streptococcus pneumoniae.

  15. [Investigation of plasmid-mediated quinolone resistance in Escherichia coli strains].

    Science.gov (United States)

    Aktepe, Orhan Cem; Aşık, Gülşah; Cetinkol, Yeliz; Biçmen, Meral; Gülay, Zeynep

    2012-01-01

    Quinolones are widely used antimicrobial agents, particularly for the treatment of infections caused by gram-negative bacilli such as E.coli. As a consequence, quinolone resistance has been increasing among this species in recent years. Bacterial resistance to quinolones usually results from mutations in the chromosomal genes which encode topoisomerases and also the expression of efflux pumps and loss of porines contributed to development of quinolone resistance. However, recent studies have shown that the spread and increase of quinolone resistance may be due to the transfer of plasmid-mediated genes. To date, three groups of plasmid-mediated quinolone resistance genes, namely qnr, aac(6')-Ib-cr, and qepA, have been described. The aim of this study was to investigate the presence of plasmid-mediated quinolone resistance genes in E.coli clinical isolates. A total of 112 quinolone-resistant E.coli strains isolated from different clinical specimens (84 urine, 16 blood, 10 wound, 2 bronchoalveolar lavage) of which 78 (69.6%) were extended-spectrum beta-lactamase (ESBL) positive, in Afyon Kocatepe University Hospital, Microbiology Laboratory were included in the study. In the isolates, qnrA, qnrB, qnrS, qnrC, qepA, and aac(6')-1b-cr plasmid genes were analysed by polymerase chain reaction (PCR). After aac(6')- 1b determinant was amplified by PCR, all aac(6')-1b positive amplicons were analyzed by digestion with BseGI restriction enzyme to identify aac(6')-1b-cr variant. It was found that, none of the strains horboured qnrA, qnrB, qnrS, qnrC and qepA genes, however, plasmid-mediated quinolone resistance gene aac(6')-1b-cr was found positive in 59.8% (67/112) of the strains. It was notable that 86.6% (58/67) of those isolates were ESBL producers. The rates of quinolone resistance among E.coli isolates infections were high in our region and an increasing trend has been observed in recent years. Our data indicated that the presence of plasmid- mediated resistance genes

  16. Quantifying Pseudomonas aeruginosa quinolones and examining their interactions with lipids.

    Science.gov (United States)

    Palmer, Gregory C; Schertzer, Jeffrey W; Mashburn-Warren, Lauren; Whiteley, Marvin

    2011-01-01

    Pseudomonas aeruginosa produces a quorum sensing molecule termed the Pseudomonas Quinolone Signal (2-heptyl-3-hydroxy-4-quinolone; PQS) that regulates an array of genes involved in virulence. This chapter addresses four related techniques useful for detecting and quantifying PQS. First, extraction of PQS from complex mixtures (e.g. cell cultures) is described. Separation of PQS from extracts by Thin-Layer Chromatography (TLC) is used in combination with the natural fluorescence of the molecule for quantification. A second separation technique for the PQS precursor HHQ using High-Performance Liquid Chromatography (HPLC) is also described, and this assay exploits the molecule's characteristic absorbance for quantification. A third method for quantification of PQS from simple mixtures (e.g. enzyme assays) using fluorescence is outlined. Finally, a protocol for determining PQS interactions with membrane lipids through Fluorescence Resonance Energy Transfer (FRET) is presented. These techniques allow for quantification and characterization of PQS from diverse environments, a prerequisite to understanding the biological functions of QS molecules.

  17. Quinolone-resistant Escherichia coli in Poultry Farming.

    Science.gov (United States)

    Hricová, Kristýna; Röderová, Magdaléna; Pudová, Vendula; Hanulík, Vojtěch; Halová, Dana; Julínková, Pavla; Dolejská, Monika; Papoušek, Ivo; Bardoň, Jan

    2017-06-01

    Increasing bacterial resistance to quinolone antibiotics is apparent in both humans and animals. For humans, a potential source of resistant bacteria may be animals or their products entering the human food chain, for example poultry. Between July 2013 and September 2014, samples were collected and analyzed in the Moravian regions of the Czech Republic to isolate the bacterium Escherichia coli. As a result, 212 E. coli isolates were obtained comprising 126 environmental isolates from poultry houses and 86 isolates from cloacal swabs from market-weight turkeys. Subsequently, the E. coli isolates were tested for susceptibility to selected antibiotics. Resistance of the poultry isolates to quinolones ranged from 53% to 73%. Additionally, the presence of plasmid-mediated resistance genes was studied. The genes were confirmed in 58% of the tested strains. The data on resistance of isolates from poultry were compared with results of resistance tests in human isolates obtained in the same regions. The high levels of resistance determined by both phenotyping and genotyping methods and reported in the present study confirm the fact that the use of fluoroquinolones in poultry should be closely monitored. Copyright© by the National Institute of Public Health, Prague 2017.

  18. Potency of Animal Models in KANSEI Engineering

    Science.gov (United States)

    Ozaki, Shigeru; Hisano, Setsuji; Iwamoto, Yoshiki

    Various species of animals have been used as animal models for neuroscience and provided critical information about the brain functions. Although it seems difficult to elucidate a highly advanced function of the human brain, animal models have potency to clarify the fundamental mechanisms of emotion, decision-making and social behavior. In this review, we will pick up common animal models and point to both the merits and demerits caused by the characteristics. We will also mention that wide-ranging approaches from animal models are advantageous to understand KANSEI as well as mind in humans.

  19. Radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone and atovaquone.

    Science.gov (United States)

    Lawres, Lauren A; Garg, Aprajita; Kumar, Vidya; Bruzual, Igor; Forquer, Isaac P; Renard, Isaline; Virji, Azan Z; Boulard, Pierre; Rodriguez, Eduardo X; Allen, Alexander J; Pou, Sovitj; Wegmann, Keith W; Winter, Rolf W; Nilsen, Aaron; Mao, Jialing; Preston, Douglas A; Belperron, Alexia A; Bockenstedt, Linda K; Hinrichs, David J; Riscoe, Michael K; Doggett, J Stone; Ben Mamoun, Choukri

    2016-06-27

    Human babesiosis is a tick-borne multisystem disease caused by Babesia species of the apicomplexan phylum. Most clinical cases and fatalities of babesiosis are caused by Babesia microti Current treatment for human babesiosis consists of two drug combinations, atovaquone + azithromycin or quinine + clindamycin. These treatments are associated with adverse side effects and a significant rate of drug failure. Here, we provide evidence for radical cure of experimental babesiosis in immunodeficient mice using a combination of an endochin-like quinolone (ELQ) prodrug and atovaquone. In vivo efficacy studies in mice using ELQ-271, ELQ-316, and the ELQ-316 prodrug, ELQ-334, demonstrated excellent growth inhibitory activity against the parasite, with potency equal to that of orally administered atovaquone at 10 mg/kg. Analysis of recrudescent parasites after ELQ or atovaquone monotherapy identified genetic substitutions in the Qi or Qo sites, respectively, of the cytochrome bc1 complex. Impressively, a combination of ELQ-334 and atovaquone, at doses as low as 5.0 mg/kg each, resulted in complete clearance of the parasite with no recrudescence up to 122 d after discontinuation of therapy. These results will set the stage for future clinical evaluation of ELQ and atovaquone combination therapy for treatment of human babesiosis. © 2016 Lawres et al.

  20. N-Substituted piperazinyl quinolones as potential cytotoxic agents: structure-activity relationships study.

    Science.gov (United States)

    Foroumadi, Alireza; Emami, Saeed; Rajabalian, Saeed; Badinloo, Marziyeh; Mohammadhosseini, Negar; Shafiee, Abbas

    2009-03-01

    As part of a continuing search for new potential anticancer candidates in the piperazinyl quinolone series, the cytotoxicity evaluation of new N-substituted piperazinyl quinolones was of our interest. The growth inhibitory activities of 12 new compounds, namely N-[2-(5-chlorothiophen-2-yl)-2-oxoethyl] and N-[2-(5-chlorothiophen-2-yl)-2-oxyiminoethyl] piperazinyl quinolones 1-12 were determined against six cancer cell lines using MTT colorimetric assay. Preliminary screening showed that most of the new N-[2-(5-chlorothiophen-2-yl)ethyl]piperazinyl quinolones 4-12 containing (un)substituted oxime moiety showed significant cytotoxic activity and the modification of functionality on ethyl spacer produced a relatively minor change of activity. Thus, in the piperazinyl quinolone series, cytotoxic activity can be positively modulated through the introduction of 2-(5-chlorothiophen-2-yl)ethyl residue on the piperazine ring. The results revealed that the introduction of 2-(5-chlorothiophen-2-yl)ethyl moiety on the piperazine ring of quinolone antibacterials (ciprofloxacin, norfloxacin and enoxacin) changes the biological profile of piperazinyl quinolones from antibacterials to cytotoxic agents.

  1. Responses of plasmid-mediated quinolone resistance genes and bacterial taxa to (fluoro)quinolones-containing manure in arable soil.

    Science.gov (United States)

    Xiong, Wenguang; Sun, Yongxue; Ding, Xueyao; Zhang, Yiming; Zhong, Xiaoxia; Liang, Wenfei; Zeng, Zhenling

    2015-01-01

    The aim of the present study was to investigate the fate of plasmid-mediated quinolone resistance (PMQR) genes and the disturbance of soil bacterial communities posed by (fluoro)quinolones (FQNs)-containing manure in arable soil. Representative FQNs (enrofloxacin (ENR), ciprofloxacin (CIP) and norfloxacin (NOR)), PMQR genes (qepA, oqxA, oqxB, aac(6')-Ib-cr and qnrS) and bacterial communities in untreated soil, +manure and +manure+FQNs groups were analyzed using culture independent methods. The significantly higher abundance of oqxA, oqxB and aac(6')-Ib-cr, and significantly higher abundance of qnrS in +manure group than those in untreated soil disappeared at day 30 and day 60, respectively. All PMQR genes (oqxA, oqxB, aac(6')-Ib-cr and qnrS) dissipated 1.5-1.7 times faster in +manure group than those in +manure+FQNs group. The disturbance of soil bacterial communities posed by FQNs-containing manure was also found. The results indicated that significant effects of PMQR genes (oqxA, oqxB, aac(6')-Ib and qnrS) on arable soils introduced by manure disappeared 2 month after manure application. FQNs introduced by manure slowed down the dissipation of PMQR genes. The presence of high FQNs provided a selective advantage for species affiliated to the phylum including Acidobacteria, Verrucomicrobia and Planctomycetes while suppressing Proteobacteria and Actinobacteria.

  2. Antipneumococcal activity of DW-224a, a new quinolone, compared to those of eight other agents.

    Science.gov (United States)

    Kosowska-Shick, Klaudia; Credito, Kim; Pankuch, Glenn A; Lin, Gengrong; Bozdogan, Bülent; McGhee, Pamela; Dewasse, Bonifacio; Choi, Dong-Rack; Ryu, Jei Man; Appelbaum, Peter C

    2006-06-01

    DW-224a is a new broad-spectrum quinolone with excellent antipneumococcal activity. Agar dilution MIC was used to test the activity of DW-224a compared to those of penicillin, ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin against 353 quinolone-susceptible pneumococci. The MICs of 29 quinolone-resistant pneumococci with defined quinolone resistance mechanisms against seven quinolones and an efflux mechanism were also tested. DW-224a was the most potent quinolone against quinolone-susceptible pneumococci (MIC(50), 0.016 microg/ml; MIC(90), 0.03 microg/ml), followed by gemifloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. beta-Lactam MICs rose with those of penicillin G, and azithromycin resistance was seen mainly in strains with raised penicillin G MICs. Against the 29 quinolone-resistant strains, DW-224a had the lowest MICs (0.06 to 1 microg/ml) compared to those of gemifloxacin, clinafloxacin, moxifloxacin, gatifloxacin, levofloxacin, and ciprofloxacin. DW-224a at 2x MIC was bactericidal after 24 h against eight of nine strains tested. Other quinolones gave similar kill kinetics relative to higher MICs. Serial passages of nine strains in the presence of sub-MIC concentrations of DW-224a, moxifloxacin, levofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, amoxicillin-clavulanate, cefuroxime, and azithromycin were performed. DW-224a yielded resistant clones similar to moxifloxacin and gemifloxacin but also yielded lower MICs. Azithromycin selected resistant clones in three of the five parents tested. Amoxicillin-clavulanate and cefuroxime did not yield resistant clones after 50 days.

  3. Pseudomonas quinolone signalling system: a component of quorum sensing cascade is a crucial player in the acute urinary tract infection caused by Pseudomonas aeruginosa.

    Science.gov (United States)

    Bala, Anju; Chhibber, Sanjay; Harjai, Kusum

    2014-11-01

    Pseudomonas aeruginosa is an opportunistic pathogen which employs quorum sensing system to regulate several genes required for its survival and pathogenicity within the host. Besides acylhomoserine lactone (AHL) mediated las and rhl systems, this organism possesses Pseudomonas quinolone signalling (PQS) system based on alkyl quinolone signal molecules. The quinolone system represents another layer of sophistication in the complex quorum sensing cascade. Therefore, in the present study, we evaluated the contribution of the PQS system in the establishment of acute urinary tract infection (UTI) in the mouse model. For this, wild-type parent strain of P. aeruginosa MPAO1 and its isogenic single transposon mutant strains pqsH and pqsA were employed to induce UTI in mice. PQS molecules in the tissue homogenates of mice were detected by high performance thin layer chromatography (HP-TLC) method. Virulence of strains was assessed in terms of bacteriological count, histopathological lesions in the renal and bladder tissue and generation of pathological index markers like reactive nitrogen intermediates and malondialdehyde. HP-TLC analysis showed presence of PQS molecules in the renal and bladder tissue of mice infected with MPAO1 while no PQS was detected in case of pqsH and pqsA mutant strains. Results indicated that MPAO1 possessing fully functional PQS biosynthetic genes was highly virulent and caused acute pyelonephritis with severe inflammation and tissue destruction. On the contrary, significant reduction in the log count, mild tissue damage and declined levels of pathological markers were observed in mice infected with mutant strains as compared to MPAO1. Further among mutants, all these parameters were maximally impaired in the pqsA mutant in which synthesis of alkyl quinolones was completely abolished due to the transposon mutation in respective gene. Virulence of the pqsH mutant strain was lesser than that of the MPAO1 but higher than pqsA mutant. In addition, the

  4. New luminophor-activators based on (fluoro)quinolone antibacterials

    Energy Technology Data Exchange (ETDEWEB)

    Polishchuk, A.V. [Joint Biotechnology Laboratory, Department of Chemistry, University of Turku, BioCity 6A, FIN-20520 Turku (Finland); Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation); Karaseva, E.T. [Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation); Korpela, T. [Joint Biotechnology Laboratory, Department of Chemistry, University of Turku, BioCity 6A, FIN-20520 Turku (Finland); Karasev, V.E. [Institute of Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, pr.100-let Vladivostoku, 159, Vladivostok 690022 (Russian Federation)], E-mail: karasev@ich.dvo.ru

    2008-11-15

    It was shown that (fluoro)quinolone antibiotics form strongly fluorescent solid-state complexes with Eu(III) and Tb(III) lanthanide ions, with a wavelength red-shift beneficial for applications to greenhouse-cover polymers. Complexes with optimal properties were prepared by the mechanical activation of fine-dispersed composite mixtures with the lanthanide salts. The spectral properties, photo-stability to UV-light, and compatibility with the polyethylene matrix were investigated. The formulation additives of the tablet forms of the antibiotic medicines did not quench the fluorescence from the lanthanide ions. Therefore, the outdated drug forms of the antibiotics can serve as cheap recyclable sources for the covering material of greenhouses. In addition, diphenylguanidine (DPG) was investigated as a coligand. DPG enhanced fluorescence of the fluoroquinolone complexes by decreasing the non-radiative energy loss through O-H vibration of H{sub 2}O.

  5. Quinolones for the Treatment of Neisseria Gonorrhoeae and Chlamydia Trachomatis

    Directory of Open Access Journals (Sweden)

    Sebastian Faro

    1993-01-01

    Full Text Available The most commonly sexually transmitted bacteria are Neisseria gonorrhoeae and Chlamydia trachomatis. The quinolones ofloxacin and ciprofloxacin have been shown to have activity against both of these bacteria in vitro and in vivo. Ofloxacin is particularly well suited for the treatment of N. gonorrhoeae and C. trachomatis cervical infection, which can be considered the earliest manifestation of pelvic inflammatory disease (PID. Not only can ofloxacin be effectively used as a single agent, it is also useful in treating urinary tract infections caused by Enterobacteriaceae. Although it has moderate activity against anaerobes in general, ofloxacin does have activity against the anaerobes commonly isolated from female patients with soft tissue pelvic infections. Thus, ofloxacin has the potential for being utilized to treat early salpingitis.

  6. Overcoming target-mediated quinolone resistance in topoisomerase IV by introducing metal-ion-independent drug-enzyme interactions.

    Science.gov (United States)

    Aldred, Katie J; Schwanz, Heidi A; Li, Gangqin; McPherson, Sylvia A; Turnbough, Charles L; Kerns, Robert J; Osheroff, Neil

    2013-12-20

    Quinolones, which target gyrase and topoisomerase IV, are the most widely prescribed antibacterials worldwide. Unfortunately, their use is threatened by the increasing prevalence of target-mediated drug resistance. Greater than 90% of mutations that confer quinolone resistance act by disrupting enzyme-drug interactions coordinated by a critical water-metal ion bridge. Quinazolinediones are quinolone-like drugs but lack the skeletal features necessary to support the bridge interaction. These compounds are of clinical interest, however, because they retain activity against the most common quinolone resistance mutations. We utilized a chemical biology approach to determine how quinazolinediones overcome quinolone resistance in Bacillus anthracis topoisomerase IV. Quinazolinediones that retain activity against quinolone-resistant topoisomerase IV do so primarily by establishing novel interactions through the C7 substituent, rather than the drug skeleton. Because some quinolones are highly active against human topoisomerase IIα, we also determined how clinically relevant quinolones discriminate between the bacterial and human enzymes. Clinically relevant quinolones display poor activity against topoisomerase IIα because the human enzyme cannot support drug interactions mediated by the water-metal ion bridge. However, the inclusion of substituents that allow quinazolinediones to overcome topoisomerase IV-mediated quinolone resistance can cause cross-reactivity against topoisomerase IIα. Therefore, a major challenge in designing drugs that overcome quinolone resistance lies in the ability to identify substituents that mediate strong interactions with the bacterial, but not the human, enzymes. On the basis of our understanding of quinolone-enzyme interactions, we have identified three compounds that display high activity against quinolone-resistant B. anthracis topoisomerase IV but low activity against human topoisomerase IIα.

  7. The Impact of Antibiotic Stewardship Programs in Combating Quinolone Resistance: A Systematic Review and Recommendations for More Efficient Interventions.

    Science.gov (United States)

    Pitiriga, Vasiliki; Vrioni, Georgia; Saroglou, George; Tsakris, Athanasios

    2017-04-01

    Quinolones are among the most commonly prescribed antibiotics worldwide. A clear relationship has been demonstrated between excessive quinolone use and the steady increase in the incidence of quinolone-resistant bacterial pathogens, both in hospital and community sites. In addition, exposure to quinolones has been associated with colonization and infection with healthcare-associated pathogens such as methicillin-resistant Staphylococcus aureus and Clostridium difficile in hospitalized patients. Therefore, the management of quinolone prescribing in hospitals through antibiotic stewardship programs is considered crucial. Although suggestions have been made by previous studies on the positive impact of stewardship programs concerning the emergence and spread of multidrug-resistant bacteria at hospital level, the association of quinolone-targeted interventions with reduction of quinolone resistance is vague. The purpose of this article was to evaluate the impact of stewardship interventions on quinolone resistance rates and healthcare-associated infections, through a literature review using systematic methods to identify and select the appropriate studies. Recommendations for improvements in quinolone-targeted stewardship programs are also proposed. Efforts in battling quinolone resistance should combine various interventions such as restriction formulary policies, prospective audits with feedback to prescribers, infection prevention and control measures, prompt detection of low-level resistance, educational programs, and guidelines for optimal quinolone usage. However, the effectiveness of such strategies should be assessed by properly designed and conducted clinical trials. Finally, novel approaches in diagnostic stewardship for rapidly detecting bacterial resistance, including PCR-based techniques, mass spectrometry, microarrays, and whole-genome sequencing as well as the prompt investigation on the clonality of quinolone-resistant strains, will strengthen our

  8. Differentiation in quinolone resistance by virulence genotype in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Melissa Agnello

    Full Text Available Pseudomonas aeruginosa is a leading pathogen that has become increasingly resistant to the fluoroquinolone antibiotics due to widespread prescribing. Adverse outcomes have been shown for patients infected with fluoroquinolone-resistant strains. The type III secretion system (TTSS is a major virulence determinant during acute infections through the injection of effector toxins into host cells. Most strains exhibit a unique TTSS virulence genotype defined by the presence of either exoS or exoU gene encoding two of the effector toxins, ExoS and ExoU, respectively. Specific TTSS effector genotype has been shown previously to differentially impact virulence in pneumonia. In this study, we examined the relationship between TTSS effector genotype and fluoroquinolone resistance mechanisms in a collection of 270 respiratory isolates. We found that a higher proportion of exoU+ strains were fluoroquinolone-resistant compared to exoS+ strains (63% vs 49%, p = 0.03 despite its lower overall prevalence (38% exoU+ vs 56% exoS+. Results from sequencing the quinolone resistance determining regions (QRDRs of the 4 target genes (gyrA, gyrB, parC, parE indicated that strains containing the exoU gene were more likely to acquire ≥ 2 mutations than exoS+ strains at MICs ≤ 8 µg/ml (13% vs none and twice as likely to have mutations in both gyrA and parC than exoS+ strains (48% vs 24% p = 0.0439. Our findings indicate that P. aeruginosa strains differentially develop resistance-conferring mutations that correlate with TTSS effector genotype and the more virulent exoU+ subpopulation. Differences in mutational processes by virulence genotype that were observed suggest co-evolution of resistance and virulence traits favoring a more virulent genotype in the quinolone-rich clinical environment.

  9. Chemical structure and pharmacokinetics of novel quinolone agents represented by avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and nemonoxacin.

    Science.gov (United States)

    Kocsis, Bela; Domokos, J; Szabo, D

    2016-05-23

    Quinolones are potent antimicrobial agents with a basic chemical structure of bicyclic ring. Fluorine atom at position C-6 and various substitutions on the basic quinolone structure yielded fluoroquinolones, namely norfloxacin, ciprofloxacin, levofloxacin, moxifloxacin and numerous other agents. The target molecules of quinolones and fluoroquinolones are bacterial gyrase and topoisomerase IV enzymes. Broad-spectrum and excellent tissue penetration make fluoroquinolones potent agents but their toxic side effects and increasing number of resistant pathogens set limits on their use. This review focuses on recent advances concerning quinolones and fluoroquinolones, we will be summarising chemical structure, mode of action, pharmacokinetic properties and toxicity. We will be describing fluoroquinolones introduced in clinical trials, namely avarofloxacin, delafloxacin, finafloxacin, zabofloxacin and non-fluorinated nemonoxacin. These agents have been proved to have enhanced antibacterial effect even against ciprofloxacin resistant pathogens, and found to be well tolerated in both oral and parenteral administrations. These features are going to make them potential antimicrobial agents in the future.

  10. Evaluating the impact of a novel restricted reimbursement policy for quinolone antibiotics: A time series analysis

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    Manns Braden

    2012-08-01

    Full Text Available Abstract Background Publicly-funded drug plans often use prior authorization policies to limit drug prescribing. To guide physician prescribing of a class of antibiotics with broad antimicrobial activity (quinolone antibiotics in accordance with new prescribing guidelines, Alberta’s provincial health ministry implemented a new mechanism for formulary restriction entitled the optional special authorization (OSA program. We conducted an observational study to determine the impact of this new formulary restriction policy on antimicrobial prescription rates as well as any clinical consequences. Methods Quinolone antibiotic use, and adherence with quinolone prescribing guidelines, was assessed before and after implementation of the OSA program in patients with common outpatient infections using an administrative data cohort and a chart review cohort, respectively. At the same time this policy was implemented to limit quinolone prescribing, two new quinolone antibiotics were added to the formulary. Using administrative data, we analysed a total of 397,534 unique index visits with regard to overall antibiotic utilization, and through chart review, we analysed 1681 charts of patients with infections of interest to determine the indications for quinolone usage. Results Using segmented regression models adjusting for age, sex and physician enrollment in the OSA program, there was no statistically significant change in the monthly rate of all quinolone use (−3.5 (95% CI −5.5, 1.4 prescriptions per 1000 index visits following implementation of the OSA program (p = 0.74. There was a significant level change in the rate of quinolone antibiotic use for urinary tract infection (−33.6 (95% CI: -23.8, -43.4 prescriptions and upper respiratory tract infection (−16.1 (95%CI: -11.6, -20.6 prescriptions per 1000 index visits. Among quinolone prescriptions identified on chart review, 42.5% and 58.5% were consistent with formulary guidelines before and

  11. Dynamics of Quinolone Resistance in Fecal Escherichia coli of Finishing Pigs after Ciprofloxacin Administration

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    Huang, Kang; Xu, Chang-Wen; Zeng, Bo; XIA, Qing-Qing; Zhang, An-Yun; LEI, Chang-Wei; Guan, Zhong-Bin; Cheng, Han; Wang, Hong-ning

    2014-01-01

    ABSTRACT Escherichia coli resistance to quinolones has now become a serious issue in large-scale pig farms of China. It is necessary to study the dynamics of quinolone resistance in fecal Escherichia coli of pigs after antimicrobial administration. Here, we present the hypothesis that the emergence of resistance in pigs requires drug accumulation for 7 days or more. To test this hypothesis, 26 pigs (90 days old, about 30 kg) not fed any antimicrobial after weaning were selected and divided in...

  12. Antimalarial therapy selection for quinolone resistance among Escherichia coli in the absence of quinolone exposure, in tropical South America.

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    Ross J Davidson

    Full Text Available BACKGROUND: Bacterial resistance to antibiotics is thought to develop only in the presence of antibiotic pressure. Here we show evidence to suggest that fluoroquinolone resistance in Escherichia coli has developed in the absence of fluoroquinolone use. METHODS: Over 4 years, outreach clinic attendees in one moderately remote and five very remote villages in rural Guyana were surveyed for the presence of rectal carriage of ciprofloxacin-resistant gram-negative bacilli (GNB. Drinking water was tested for the presence of resistant GNB by culture, and the presence of antibacterial agents and chloroquine by HPLC. The development of ciprofloxacin resistance in E. coli was examined after serial exposure to chloroquine. Patient and laboratory isolates of E. coli resistant to ciprofloxacin were assessed by PCR-sequencing for quinolone-resistance-determining-region (QRDR mutations. RESULTS: In the very remote villages, 4.8% of patients carried ciprofloxacin-resistant E. coli with QRDR mutations despite no local availability of quinolones. However, there had been extensive local use of chloroquine, with higher prevalence of resistance seen in the villages shortly after a Plasmodium vivax epidemic (p<0.01. Antibacterial agents were not found in the drinking water, but chloroquine was demonstrated to be present. Chloroquine was found to inhibit the growth of E. coli in vitro. Replica plating demonstrated that 2-step QRDR mutations could be induced in E. coli in response to chloroquine. CONCLUSIONS: In these remote communities, the heavy use of chloroquine to treat malaria likely selected for ciprofloxacin resistance in E. coli. This may be an important public health problem in malarious areas.

  13. Occurrence of (fluoro)quinolones and (fluoro)quinolone resistance in soil receiving swine manure for 11 years.

    Science.gov (United States)

    Xu, Yonggang; Yu, Wantai; Ma, Qiang; Zhou, Hua

    2015-10-15

    Because of the widespread use of antibiotics in animal breeding, the agricultural application of animal manure can lead to the introduction of antibiotics, antibiotic-resistant bacteria and antibiotic resistance genes to the soil and surrounding environment, which may pose a threat to public health. In this study, we investigated the status of (fluoro)quinolone (FQ) residues and FQ resistance levels in soil with and without receiving long-term swine manure. Six FQs (pipemidic acid, lomefloxacin, enrofloxacin, norfloxacin, ciprofloxacin, and ofloxacin) were only detected in manured soil, with individual concentrations ranging from below the detection limit to 27.2 μg kg(-1) and increasing with the increase in swine manure application rates. Higher load rates of swine manure yielded a higher number of ciprofloxacin-resistant (CIPr) bacteria after spreading. A total of 24 CIPr bacterial isolates were obtained from the tested soil, which belonged to four phyla (Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes) or were related to nine different genera. Only 18 isolates from manured soil were positive for five plasmid-mediated quinolone resistance (PMQR) genes (aac(6')-Ib-cr, qnrD, qepA, oqxA, and oqxB). To our knowledge, this study is the first to examine the occurrence of PMQR genes in FQ-resistant bacteria from the soil environment. A similar result was observed for the total DNA from soil, with the exception of aac(6')-Ib being detected in the control sample. The absolute and relative abundances of total PMQR genes also increased with fertilization quantity. Significant correlations were observed between FQ resistance levels and FQ concentrations. These results indicated that the agricultural application of swine manure led to FQ residues and enhanced FQ resistance. This investigation provides baseline data on FQ resistance profiles in soils receiving long-term swine manure. Copyright © 2015. Published by Elsevier B.V.

  14. [Multiresidue determination of quinolones in animal and fishery products by HPLC].

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    Chonan, Takao; Fujimoto, Toru; Inoue, Maki; Tazawa, Teijiro; Ogawa, Hiroshi

    2008-06-01

    A simple and rapid multiresidue method was developed for the determination of twelve quinolones (ciprofloxacin, danofloxacin, difloxacin, enrofloxacin, flumequine, marbofloxacin, nalidixic acid, norfloxacin, ofloxacin, orbifloxacin, oxolinic acid and sarafloxacin) in muscle, liver, chicken eggs, milk, prawn and rainbow trout. The quinolones were extracted from a sample with acetonitrile-water (95 : 5). A fifth part of the filtered extract was diluted with water to keep the acetonitrile ratio at ca. 60%, and passed through a C18 mini-column. The eluate was evaporated to dryness, and the residues were dissolved in methanol-water (30 : 70) for HPLC analysis. The quinolones were separated on a Inertsil ODS-3V column (4.6 mm i.d.x250 mm) with a gradient system of 0.1% phosphoric acid-acetonitrile as the mobile phase, with fluorescence detection.No interfering peak was found on the chromatograms of animal and fishery products, except for milk. The recoveries of the quinolones were over 60% from the animal and fishery products fortified at 0.1 microg/g, and the quantification limits of the quinolones were 0.005 microg/g. This proposed method was found to be effective and suitable for the screening of the quinolones in animal and fishery products.

  15. Genotoxicity of quinolone antibiotics in chlorination disinfection treatment: formation and QSAR simulation.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Du, Yuguo

    2016-10-01

    Lots of unexpected disinfection by-products were formed during the chlorination disinfection of contaminated water bodies, leading to a potential threat to human health and ecological safety. In this study, SOS/umu assay was used to trace the genotoxicity variation of 20 quinolone compounds during the chlorination disinfection. Furthermore, two- and three-dimensional quantitative structure-activity relationship models were developed based on the electronic and hydrophobic properties of the quinolones, which were used to quantify the impact of the different structural features of the compounds on their genotoxicity variation. The results revealed that quinolones bearing hydrophilic substituents with less H-bond donors and negative charge at the 1-position of the quinolone ring exhibited a positive correlation with genotoxicity elevation. More notably, the chlorination of quinolones in both ultrapure water and secondary effluent matrices provided comparable levels of genotoxicity, indicating that our research could potentially be used to evaluate the environmental risk of quinolone antibiotics in chlorination disinfection treatment.

  16. 4-Quinolone-3-carboxylic acids as cell-permeable inhibitors of protein tyrosine phosphatase 1B.

    Science.gov (United States)

    Zhi, Ying; Gao, Li-Xin; Jin, Yi; Tang, Chun-Lan; Li, Jing-Ya; Li, Jia; Long, Ya-Qiu

    2014-07-15

    Protein tyrosine phosphatase 1B is a negative regulator in the insulin and leptin signaling pathways, and has emerged as an attractive target for the treatment of type 2 diabetes and obesity. However, the essential pharmacophore of charged phosphotyrosine or its mimetic confer low selectivity and poor cell permeability. Starting from our previously reported aryl diketoacid-based PTP1B inhibitors, a drug-like scaffold of 4-quinolone-3-carboxylic acid was introduced for the first time as a novel surrogate of phosphotyrosine. An optimal combination of hydrophobic groups installed at C-6, N-1 and C-3 positions of the quinolone motif afforded potent PTP1B inhibitors with low micromolar IC50 values. These 4-quinolone-3-carboxylate based PTP1B inhibitors displayed a 2-10 fold selectivity over a panel of PTP's. Furthermore, the bidentate inhibitors of 4-quinolone-3-carboxylic acids conjugated with aryl diketoacid or salicylic acid were cell permeable and enhanced insulin signaling in CHO/hIR cells. The kinetic studies and molecular modeling suggest that the 4-quinolone-3-carboxylates act as competitive inhibitors by binding to the PTP1B active site in the WPD loop closed conformation. Taken together, our study shows that the 4-quinolone-3-carboxylic acid derivatives exhibit improved pharmacological properties over previously described PTB1B inhibitors and warrant further preclinical studies.

  17. Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.

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    Jérémie Piton

    Full Text Available Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA.

  18. Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia.

    Science.gov (United States)

    García-León, Guillermo; Salgado, Fabiola; Oliveros, Juan Carlos; Sánchez, María Blanca; Martínez, José Luis

    2014-05-01

    To analyse whether the mutation-driven resistance-acquisition potential of a given bacterium might be a function of its intrinsic resistome, quinolones were used as selective agents and Stenotrophomonas maltophilia was chosen as a bacterial model. S. maltophilia has two elements - SmQnr and SmeDEF - that are important in intrinsic resistance to quinolones. Using a battery of mutants in which either or both of these elements had been removed, the apparent mutation frequency for quinolone resistance and the phenotype of the selected mutants were found to be related to the intrinsic resistome and also depended on the concentration of the selector. Most mutants had phenotypes compatible with the overexpression of multidrug efflux pump(s); SmeDEF overexpression was the most common cause of quinolone resistance. Whole genome sequencing showed that mutations of the SmeRv regulator, which result in the overexpression of the efflux pump SmeVWX, are the cause of quinolone resistance in mutants not overexpressing SmeDEF. These results indicate that the development of mutation-driven antibiotic resistance is highly dependent on the intrinsic resistome, which, at least for synthetic antibiotics such as quinolones, did not develop as a response to the presence of antibiotics in the natural ecosystems in which S. maltophilia evolved.

  19. Screening of quinolone antibiotic residues in chicken meat and beef sold in the markets of Ankara, Turkey.

    Science.gov (United States)

    Er, Buket; Onurdag, Fatma Kaynak; Demirhan, Burak; Ozgacar, Selda Özgen; Oktem, Aysel Bayhan; Abbasoglu, Ufuk

    2013-08-01

    This study aimed to find the effects of quinolone antibiotics in chicken and beef used in Ankara, Turkey. Total number of 127 chicken and 104 beef meat samples were collected randomly from local markets for analysis. Extraction and determination of quinolones were made by ELISA procedure. One hundred eighteen of 231 (51.1%) examined chicken meat and beef samples were found to contain quinolone antibiotic residue. Among the chicken meat and beef samples, 58 (45.7%) of chicken meat samples and 60 (57.7%) of beef meat samples were positive for quinolones, respectively. The mean levels (±SE) of quinolones were found to be 30.81 ± 0.45 µg/kg and 6.64 ± 1.11 µg/kg in chicken and beef samples, respectively. This study indicated that some chicken and beef meat sold in Ankara contains residues of quinolone antibiotics.

  20. Rapid determination of quinolones in cosmetic products by ultra high performance liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Liu, Shao-Ying; Huang, Xi-Hui; Wang, Xiao-Fang; Jin, Quan; Zhu, Guo-Nian

    2014-05-01

    This study developed an improved analytical method for the simultaneous quantification of 13 quinolones in cosmetics by ultra high performance liquid chromatography combined with ESI triple quadrupole MS/MS under the multiple reaction monitoring mode. The analytes were extracted and purified by using an SPE cartridge. The limits of quantification ranged from 0.03 to 3.02 μg/kg. The precision for determining the quinolones was quinolones in real cosmetic samples.

  1. Quinolone resistance in absence of selective pressure: the experience of a very remote community in the Amazon forest.

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    Lucia Pallecchi

    Full Text Available BACKGROUND: Quinolones are potent broad-spectrum bactericidal agents increasingly employed also in resource-limited countries. Resistance to quinolones is an increasing problem, known to be strongly associated with quinolone exposure. We report on the emergence of quinolone resistance in a very remote community in the Amazon forest, where quinolones have never been used and quinolone resistance was absent in 2002. METHODS: The community exhibited a considerable level of geographical isolation, limited contact with the exterior and minimal antibiotic use (not including quinolones. In December 2009, fecal carriage of antibiotic resistant Escherichia coli was investigated in 120 of the 140 inhabitants, and in 48 animals reared in the community. All fluoroquinolone-resistant isolates were genotyped and characterized for the mechanisms of plasmid- and chromosomal-mediated quinolone resistance. PRINCIPAL FINDINGS: Despite the characteristics of the community remained substantially unchanged during the period 2002-2009, carriage of quinolone-resistant E. coli was found to be common in 2009 both in humans (45% nalidixic acid, 14% ciprofloxacin and animals (54% nalidixic acid, 23% ciprofloxacin. Ciprofloxacin-resistant isolates of human and animal origin showed multidrug resistance phenotypes, a high level of genetic heterogeneity, and a combination of GyrA (Ser83Leu and Asp87Asn and ParC (Ser80Ile substitutions commonly observed in fluoroquinolone-resistant clinical isolates of E. coli. CONCLUSIONS: Remoteness and absence of antibiotic selective pressure did not protect the community from the remarkable emergence of quinolone resistance in E. coli. Introduction of the resistant strains from antibiotic-exposed settings is the most likely source, while persistence and dissemination in the absence of quinolone exposure is likely mostly related with poor sanitation. Interventions aimed at reducing the spreading of resistant isolates (by improving sanitation

  2. Rh(III) and Ru(II)-catalyzed site-selective C-H alkynylation of quinolones.

    Science.gov (United States)

    Kang, Dahye; Hong, Sungwoo

    2015-04-17

    C2- and C5-alkynylated quinolone scaffolds are core structures of numerous biologically active molecules. Utilizing TIPS-EBX as an alkynylating agent, we have developed an efficient and site-selective C5 alkynylation of 4-quinolones that is directed by the weakly coordinating carbonyl group. In addition, Ru(II) catalyzed C2-selective alkynylation was successfully realized via N-pyrimidyl group-directed cross-couplings to access valuable C2-alkynylated 4-quinolones. This strategy provides direct access to the C2 or C5 alkynylated 4-quinolones. Furthermore, the reaction was applied to isoquinolones for C3-selective alkynylation.

  3. Actualidad de las quinolonas Present situation of quinolones

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    Manuel Cué Brugueras

    2005-04-01

    Full Text Available Las quinolonas son los antimicrobianos que han tenido un mayor desarrollo en los últimos años. Después de obtenerse el ácido nalidíxico, en 1962, se desarrollaron varios compuestos con características muy similares, que solo se establecieron como antisépticos urinarios, y que constituyeron la primera generación de quinolonas, hasta que en 1978, mediante la adición de un grupo piperacinil en posición 7 y un átomo de flúor en posición 6 comenzó a desarrollarse un conjunto de agentes antibacterianos llamados piperacinil fluoroquinolonas o simplemente fluoroquinolonas. El primero de ellos fue el norfloxacino, con el cual se logró una mayor actividad antimicrobiana del grupo y su uso sistémico. Durante años las fluroquinolonas fueron consideradas como un grupo homogéneo de antibióticos, con propiedades semejantes y, por tanto, como la segunda y última posibilidad de generación de quinolonas, pero las posibilidades de transformación de su estructura química ha producido un desarrollo vertiginoso de este grupo, que lo ha convertido en el más acelerado dentro de los antibióticos, con compuestos de mayor espectro antibacteriano, penetración tisular y seguridad, y con menor manifestación de resistencia antimicrobiana, demostrada hasta el presente, lo cual ha hecho que actualmente existan 4 generaciones de quinolonas, que se haya ampliado su uso y que continúe su desarrollo. Por tal motivo, se presenta una revisión que incluye espectro y mecanismo de acción, resistencia bacteriana, farmacodinamia y farmacocinética, interacciones medicamentosas, efectos adversos, indicaciones y dosificación de las más usadas.The quinolones are antimicrobial agents that have attained their highest development in the last years. After obtaining nalidixic acid, in 1962, several compounds were developed with similar characteristics that were only established as urinary antiseptics and that were the first generation of quinolones until 1978, when

  4. [The history of the development and changes of quinolone antibacterial agents].

    Science.gov (United States)

    Takahashi, Hisashi; Hayakawa, Isao; Akimoto, Takeshi

    2003-01-01

    The quinolones, especially the new quinolones (the 6-fluoroquinolones), are the synthetic antibacterial agents to rival the Beta-lactam and the macrolide antibacterials for impact in clinical usage in the antibacterial therapeutic field. They have a broad antibacterial spectrum of activity against Gram-positive, Gram-negative and mycobacterial pathogens as well as anaerobes. Further, they show good-to-moderate oral absorption and tissue penetration with favorable pharmacokinetics in humans resulting in high clinical efficacy in the treatment of many kinds of infections. They also exhibit excellent safety profiles as well as those of oral Beta-lactam antibiotics. The bacterial effects of quinolones inhibit the function of bacterial DNA gyrase and topoisomerase IV. The history of the development of the quinolones originated from nalidixic acid (NA), developed in 1962. In addition, the breakthrough in the drug design for the scaffold and the basic side chains have allowed improvements to be made to the first new quinolone, norfloxacin (NFLX), patented in 1978. Although currently more than 10,000 compounds have been already synthesized in the world, only two percent of them were developed and tested in clinical studies. Furthermore, out of all these compounds, only twenty have been successfully launched into the market. In this paper, the history of the development and changes of the quinolones are described from the first quinolone, NA, via, the first new quinolone (6-fluorinated quinolone) NFLX, to the latest extended-spectrum quinolone antibacterial agents against multi-drug resistant bacterial infections. NA has only modest activity against Gram-negative bacteria and low oral absorption, therefore a suitable candidate for treatment of systemic infections (UTIs) is required. Since the original discovery of NA, a series of quinolones, which are referred to as the old quinolones, have been developed leading to the first new quinolone, NFLX, with moderate improvements

  5. MATHEMATICAL MODELING FOR ERYTHROMYCIN POTENCY DETERMINATION OF MASTIKER

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    Victorita Burghelea

    2016-12-01

    Full Text Available Mastiker E is an antibacterial suspension for intramammary infusion in cattle mastitis. The active drug is erythromycin, a macrolide antibiotic. The main characteristic of commercial product is erythromycin potency. The potency of erythromycin is estimated by comparing the inhibition of growth of sensitive micro-organisms produced by known concentrations of the antibiotic to be examined and a reference substance. The validation study aims to demonstrate the determination of the potency of erythromycin, it is an appropriate analytical method, reproducible and meets the quality requirements of Mastiker product. The paper establishes the performance characteristics of the method considered and identify the factors that influence these characteristics. The diameters of inhibition zones, directly proportional to the logarithm of the concentration of the antibiotic used for the assay, measured and calculated using statistical methods (Combistats Soft. The assay is designed in such a way that the mathematical model on which the potency equation is based can be proved to be valid. A parallel-line model is chosen. The two log dose response lines of the preparation under examination and the standard preparation are parallel; they are rectilinear over the range of doses used in the calculation. These conditions are verified by validity tests for a given probability (P = 0.05. The test is not valid unless the confidence limits (P = 0.95 are not less than 50% and not more than 200% of the estimated potency. The estimated potency is not less than 95% and not more than 105% of the stated potency. The stated potency is not less than 50.000 IU/g. The validation procedure includes details on protocol working to determine the potency of erythromycin, validation criteria, experimental results, mathematical modeling for determining the potency, inter laboratory comparisons.

  6. Prion potency in stem cells biology.

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    Lopes, Marilene H; Santos, Tiago G

    2012-01-01

    Prion protein (PrP) can be considered a pivotal molecule because it interacts with several partners to perform a diverse range of critical biological functions that might differ in embryonic and adult cells. In recent years, there have been major advances in elucidating the putative role of PrP in the basic biology of stem cells in many different systems. Here, we review the evidence indicating that PrP is a key molecule involved in driving different aspects of the potency of embryonic and tissue-specific stem cells in self-perpetuation and differentiation in many cell types. It has been shown that PrP is involved in stem cell self-renewal, controlling pluripotency gene expression, proliferation, and neural and cardiomyocyte differentiation. PrP also has essential roles in distinct processes that regulate tissue-specific stem cell biology in nervous and hematopoietic systems and during muscle regeneration. Results from our own investigations have shown that PrP is able to modulate self-renewal and proliferation in neural stem cells, processes that are enhanced by PrP interactions with stress inducible protein 1 (STI1). Thus, the available data reveal the influence of PrP in acting upon the maintenance of pluripotent status or the differentiation of stem cells from the early embryogenesis through adulthood.

  7. Mechanisms of quinolone resistance and implications for human and animal health

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    Velhner Maja

    2010-01-01

    Full Text Available Quinolone antibiotics have been widely used in human and veterinary medicine. This has caused the development of resistance and difficulties in the treatment of complicated bacterial infections in humans. The resistance to quinolones develops due to chromosome mutations and it can also be transferred by plasmids. The target enzyme for quinolones in Gram-negative bacteria is Gyrasa A, while the target enzyme in Grampositive bacteria is mostly topoisomerase IV. Gyrase A consists of two subunits encoded by genes gyrA and gyrB. The function of the enzyme is to introduce negative super coiling in DNA and therefore is essential for the replication of bacteria. Quinolone resistance develops if point mutations at 83 and/or 87 codon are introduced on gyrA. Establishing a minimal inhibitory concentration (MIC to this group of antimicrobials will reveal possible mutations. Recently it was discovered that quinolone resistance is transmittable by plasmid termed PMQR (plasmid mediated quinolone resistance. The target gene marked qnr encodes a pentapeptide repeat family protein. Pentapeptide repeats form sheets, involved in protein-protein interactions. Qnr protein binds to GyrA protecting the enzyme from the inhibitory effect of ciprofloxacin. The distribution of qnr related resistance is higher in humans than in animals. In poultry, however, this type of resistance is present more than in other animals. Plasmid mediated resistance contributes to the faster spread of quinolone resistance. Proper food handling will significantly contribute to decreasing the risk from infection to which people are exposed. In medical and veterinary laboratories antimicrobial resistance monitoring in clinical and environmental isolates is advised. Since correlation between antibiotics application and antimicrobial resistance is often suggested, antimicrobial use must be under strict control of the authorities both in human and in veterinary medicine. .

  8. [Role of reactive oxygen species in the bactericidal action of quinolones--inhibitors of DNA gyrase].

    Science.gov (United States)

    Kotova, V Iu; Mironov, A S; Zavigel'skiĭ, G B

    2014-01-01

    Quinolone antibiotics inhibit DNA gyrase, but the induced degradation of chromosomal DNA is determined by a complex process of joint action quinolones and hydroxyl radical OH'. To quantify the level of stress responses and their time dependence in bacterial cells the induced specific lux-biosensors--the bacterium Escherichia coli, containing hybrid plasmids pColD'::lux; pSoxS'::lux; pKatG'::lux were used in this study. It is shown that quinolones (nalidixic acid, norfloxacin) induce SOS-response and oxidative stress with the formation of superoxide anion O2(-) in E. coli cells. The main parameters of SOS-response and oxidative stress, which depend on the quinolone concentration, are determined. Formation of superoxide anion O2(-) occurs almost simultaneously with the SOS-response. The mutant strain of E. coli sodA sodB, which do not contain active forms of superoxide dismutases SodA and SodB, is characterized by an increased resistance to quinolones as compared to the wild type cells. At high concentrations of quinolones (nalidixic acid-->20 μg/mL; norfloxacin-->500 ng/mL) their bactericidal effect is partially caused by conversion of the superoxide anion to hydrogen peroxide H2O2, conducted by superoxide dismutases SodA and SodB, which is followed by the Fenton reaction and the formation of toxic hydroxyl radical OH'. At low concentrations of quinolones (nalidixic acid--<20 μg/mL; norfloxacin--<500 ng/mL), the role of active oxygen species in the antimicrobial effect is practically nonexistent.

  9. Characterization of quinolone resistance in Salmonella enterica serovar Indiana from chickens in China.

    Science.gov (United States)

    Lu, Yan; Zhao, Hongyu; Liu, Yuqi; Zhou, Xuping; Wang, Jinyuan; Liu, Tiantian; Beier, Ross C; Hou, Xiaolin

    2015-03-01

    The aim of this study was to characterize the quinolone resistance of Salmonella enterica serovar Indiana isolated from chickens in China. A total of 293 Salmonella strains were isolated from chicken farms and slaughterhouses in Shandong province of China, and 130 (44.4%) were characterized as Salmonella enterica Indiana (chicken farms, n=52 strains; slaughter houses, n=78 strains). All isolate serotypes were tested with the Kauffmann-White classification system and examined for susceptibility to the quinolones: nalidixic acid, enrofloxacin, norfloxacin, and ciprofloxacin. The resistance of the Salmonella Indiana strains to nalidixic acid, enrofloxacin, norfloxacin, and ciprofloxacin were 100, 73.1, 71.2, and 82.7%, and 100, 59.0, 79.5, and 80.2%, respectively. Selected quinolone resistant strains were evaluated for mutations in genes (gyrA, gyrB, parC, and marA) by DNA sequencing. The gyrA mutation was found in all isolates, the parC mutation was only found in some isolates, and the gyrB and marA mutations were not observed. Quinolone resistance was evaluated in the representative isolates by screening for the quinolone resistance determinants, qnrA, qnrB, qnrS, qepA, and aac (6 ')-Ib-cr using PCR technology. The quinolone resistance determinants in Salmonella, qnrA, qnrB, qnrS, and qepA were negative by PCR, but aac(6 ')-Ib-cr had high detection rates of 90.4 and 96.2% in chicken farms and slaughterhouses, respectively. Salmonella Indiana containing the gyrA mutation was prevalent in farms and slaughterhouses and possessed a high frequency of the quinolone resistance determinant aac(6 ')-Ib-cr. These bacteria may have originated from the same source.

  10. P4 capped amides and lactams as HCV NS3 protease inhibitors with improved potency and DMPK profile

    Energy Technology Data Exchange (ETDEWEB)

    Nair, Latha G.; Sannigrahi, Mousumi; Bogen, Stephane; Pinto, Patrick; Chen, Kevin X.; Prongay, Andrew; Tong, Xiao; Cheng, K.-C.; Girijavallabhann, Viyyoor; Njoroge, F. George (Merck)

    2010-09-03

    SAR studies on the extension of P3 unit of Boceprevir (1, SCH 503034) with amides and lactams and their synthesis is described. Extensive SAR studies resulted in the identification of 36 bearing 4,4-dimethyl lactam as the new P4 cap unit with improved potency (K*{sub i}, EC 90 = 70 nM) and pharmacokinetic properties (Rat AUC (PO) = 3.52 {micro}M h) compared to 1.

  11. Effect of various storage conditions on the stability of quinolones in raw milk.

    Science.gov (United States)

    Chen, Meixia; Wen, Fang; Wang, Hui; Zheng, Nan; Wang, Jiaqi

    2016-07-01

    Research on the storage stability of antibiotic residues in milk is important for method development or validation, milk quality control and risk assessment during screening, confirmation, qualitative or quantitative analysis. This study was conducted using UPLC-MS/MS to determine the stability of six quinolones - ciprofloxacin (CIP), danofloxacin (DAN), enrofloxacin (ENR), sarafloxacin (SAR), difloxacin (DIF) and flumequine (FLU) - in raw milk stored under various conditions to investigate if quinolones degrade during storage of milk, and finally to determine optimal storage conditions for analysis and scientific risk assessment of quinolone residues in raw milk. The storage conditions included different temperatures and durations (4°C for 4, 8, 24 and 48 h; -20°C for 1, 7 and 30 days; -80°C for 1, 7 and 30 days), thawing temperatures (25, 40 and 60°C), freeze-thaw cycles (1-5), and the addition of different preservatives (sodium thiocyanate, sodium azide, potassium dichromate, bronopol and methanal). Most quinolones exhibited high stability at 4°C for up to 24 h, but began to degrade after 48 h. In addition, no degradation of quinolones was seen when milk samples were stored at -20°C for up to 7 days; however, 30 days of storage at -20°C resulted in a small amount of degradation (about 30%). Similar results were seen when samples were stored at -80°C. Moreover, no losses were observed when frozen milk samples were thawed at 25, 40 or 60°C. All the quinolones of interest, except sarafloxacin, were stable when milk samples were thawed at 40°C once and three times, but unstable after five freeze-thaw cycles. Preservatives affected the stability of quinolones, but the effects differed depending on the preservative and quinolone. The results of this study indicate optimum storage protocols for milk samples, so that residue levels reflect those at the time of initial sample analysis, and should improve surveillance programmes for quinolones in raw milk.

  12. In vitro anti-Mycobacterium avium activities of quinolones: predicted active structures and mechanistic considerations.

    Science.gov (United States)

    Klopman, G; Li, J Y; Wang, S; Pearson, A J; Chang, K; Jacobs, M R; Bajaksouzian, S; Ellner, J J

    1994-08-01

    The relationship between the structures of quinolones and their anti-Mycobacterium avium activities has been previously derived by using the Multiple Computer-Automated Structure Evaluation program. A number of substructural constraints required to overcome the resistance of most of the strains have been identified. Nineteen new quinolones which qualify under these substructural requirements were identified by the program and subsequently tested. The results show that the substructural attributes identified by the program produced a successful a priori prediction of the anti-M. avium activities of the new quinolones. All 19 quinolones were found to be active, and 4 of them are as active or better than ciprofloxacin. With these new quinolones, the updated multiple computer-automated structure evaluation program structure-activity relationship analysis has helped to uncover additional information about the nature of the substituents at the C5 and C7 positions needed for optimal inhibitory activity. A possible explanation of drug resistance based on the observation of suicide inactivation of bacterial cytochrome P-450 by the cyclopropylamine moiety has also been proposed and is discussed in this report. Furthermore, we confirm the view that the amount of the uncharged form present in a neutral pH solution plays a crucial role in the drug's penetration ability.

  13. Fluorescence quenching as a tool to investigate quinolone antibiotic interactions with bacterial protein OmpF.

    Science.gov (United States)

    Neves, Patrícia; Sousa, Isabel; Winterhalter, Mathias; Gameiro, Paula

    2009-02-01

    The outer membrane porin OmpF is an important protein for the uptake of antibiotics through the outer membrane of gram-negative bacteria; however, the possible binding sites involved in this uptake are still not recognized. Determination, at the molecular level, of the possible sites of antibiotic interaction is very important, not only to understand their mechanism of action but also to unravel bacterial resistance. Due to the intrinsic OmpF fluorescence, attributed mainly to its tryptophans (Trp(214), Trp(61)), quenching experiments were used to assess the site(s) of interaction of some quinolone antibiotics. OmpF was reconstituted in different organized structures, and the fluorescence quenching results, in the presence of two quenching agents, acrylamide and iodide, certified that acrylamide quenches Trp(61) and iodide Trp(214). Similar data, obtained in presence of the quinolones, revealed distinct behaviors for these antibiotics, with nalidixic acid interacting near Trp(214) and moxifloxacin near Trp(61). These studies, based on straightforward and quick procedures, show the existence of conformational changes in the protein in order to adapt to the different organized structures and to interact with the quinolones. The extent of reorganization of the protein in the presence of the different quinolones allowed an estimate on the sites of protein/quinolone interaction.

  14. The evidence for clonal spreading of quinolone resistance with a particular clonal complex of Campylobacter jejuni.

    Science.gov (United States)

    Kovač, J; Cadež, N; Lušicky, M; Nielsen, E Møller; Ocepek, M; Raspor, P; Možina, S Smole

    2014-12-01

    Campylobacter is the most prevalent cause of bacterial gastroenteritis worldwide and it represents a significant public health risk of increasing severity due to its escalating resistance to clinically important quinolone and macrolide antibiotics. As a zoonotic pathogen Campylobacter is transmitted along the food chain and naturally cycles from environmental waters, feedstuff, animals and food to humans. We determined antibiotic resistance profiles, as well as multilocus sequence types and flaA-SVR types for 52 C. jejuni isolated in Slovenia from human, animal, raw and cured chicken meat and water samples. Twenty-eight different sequence types, arranged in ten clonal complexes, three new allele types and five new sequence types were identified, indicating the relatively high diversity in a small group of strains. The assignment of strains from different sources to the same clonal complexes indicates their transmission along the food supply chain. The most prevalent clonal complex was CC21, which was also the genetic group with 95% of quinolone-resistant strains. Based on the genetic relatedness of these quinolone-resistant strains identified by polymerase chain reaction with a mismatch amplification mutation assay and sequencing of the quinolone resistance-determining region of the gyrA gene, we conclude that the high resistance prevalence observed indicates the local clonal spread of quinolone resistance with CC21.

  15. Introduction of quinolone resistant Escherichia coli to Swedish broiler population by imported breeding animals.

    Science.gov (United States)

    Börjesson, Stefan; Guillard, Thomas; Landén, Annica; Bengtsson, Björn; Nilsson, Oskar

    2016-10-15

    During recent years a rapid increase of quinolone resistant Escherichia coli have been noted in the Swedish broiler population, despite the lack of a known selective pressure. The current study wanted to investigate if imported breeding birds could be a source for the quinolone resistant E. coli. The occurrence of quinolone resistant E. coli was investigated, using selective cultivation with nalidixic acid, in grand-parent birds on arrival to Sweden and their progeny. In addition, sampling in hatcheries and empty cleaned poultry houses was performed. Clonality of isolates was investigated using a 10-loci multiple-locus variable number tandem repeat analysis (MLVA). To identify the genetic basis for the resistance isolates were also analysed for occurrence of plasmid-mediated quinolone resistance (PMQR) determinants and characterization of chromosomal mutations. E. coli resistant to nalidixic acid occurred in grandparent birds imported to Sweden for breeding purposes. Four predominant MLVA types were identified in isolates from grandparent birds, parent birds and broilers. However, resistant E. coli with identical MLVA patterns were also present in hatcheries and poultry houses suggesting that the environment plays a role in the occurrence. Nalidixic acid resistance was due to a mutation in the gyrA gene and no PMQR could be identified. The occurrence of identical clones in all levels of the production pyramid points to that quinolone resistant E. coli can be introduced through imported breeding birds and spread by vertical transmission to all levels of the broiler production pyramid.

  16. Semiempirical MNDO and UV Absorption Studies on Tautomerism of 2-Quinolones

    Science.gov (United States)

    Mirek, Julian; Syguła, Andrzej

    1982-11-01

    Semiempirical MNDO calculations with geometry optimization were carried out for seven 4-X-2-quinolone tautomers (X = H, CH3, Cl, OCH3, N(CH3)2, COOH, COOCH3). The results show that 2-hydroxyquinolines are less stabilized compared to 2-quinoIones than 2-hydroxypyridines vs. 2-pyridones. The earlier estimated correction applied to these MNDO results suggests that 4-X-2-quinolones have lower chemical binding energies than the corresponding 4-X-2- hydroxyquinolines by ca. 2.1-3.3 kcal/mol. It is additionally shown that the substituent in position 4 does not influence significantly the relative stabilities of the tautomers. The results of the calculations are verified by UV absorption studies of diluted decane solutions of 2-quinolones at ca. 120°. CNDO/S-Cl-1 calculations based on the optimal MNDO geometries were carried out for 4-X-2- quinolone tautomers. The results generally agree well with the experimental data. A disagreement of the data for 4-COOR-2-quinolones is rationalized.

  17. Study of the luminescence behavior of seven quinolones on a paper substrate

    Energy Technology Data Exchange (ETDEWEB)

    Li Junfen [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China)]. E-mail: fenjunli@sina.com; Li Jianqing [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); Shuang Shaomin [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China); Dong Chuan [Institute of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006 (China)]. E-mail: dc@sxu.edu.cn

    2005-08-29

    Studies on the luminescence spectra behaviors of seven quinines on solid substrate (SS-RTP) were performed. Experimental conditions, such as heavy atom type, pH and drying time of the sample, etc. on solid substrate room temperature phosphorescence (SS-RTP) or solid substrate delayed fluorescence (SS-DF), were studied in detail. CdCl{sub 2} could induce strongest RTP or DF emission of these quinolones. In addition, a comparative study on the spectral behavior of seven quinolones was given, including low temperature phosphorescence (LTP), low temperature fluorescence (LTF) and spectra methioned above. New determination methods for the analysis of seven quinolones by solid substrate room temperature fluorescence (SS-RTF), SS-RTP or SS-DF with filter paper as solid substrate were presented. Analytical characteristics of these methods of seven quinolones were studied. The linear dynamic ranges (LDR), the limit of detection (LOD) and the relative standard deviation (R.S.D.) were valued. Recoveries of seven quinolones in human urine samples were from 98.1% to 104.3%.

  18. Protective effect of Qnr on agents other than quinolones that target DNA gyrase.

    Science.gov (United States)

    Jacoby, George A; Corcoran, Marian A; Hooper, David C

    2015-11-01

    Qnr is a plasmid-encoded and chromosomally determined protein that protects DNA gyrase and topoisomerase IV from inhibition by quinolones. Despite its prevalence worldwide and existence prior to the discovery of quinolones, its native function is not known. Other synthetic compounds and natural products also target bacterial topoisomerases. A number were studied as molecular probes to gain insight into how Qnr acts. Qnr blocked inhibition by synthetic compounds with somewhat quinolone-like structure that target the GyrA subunit, such as the 2-pyridone ABT-719, the quinazoline-2,4-dione PD 0305970, and the spiropyrimidinetrione pyrazinyl-alkynyl-tetrahydroquinoline (PAT), indicating that Qnr is not strictly quinolone specific, but Qnr did not protect against GyrA-targeting simocyclinone D8 despite evidence that both simocyclinone D8 and Qnr affect DNA binding to gyrase. Qnr did not affect the activity of tricyclic pyrimidoindole or pyrazolopyridones, synthetic inhibitors of the GyrB subunit, or nonsynthetic GyrB inhibitors, such as coumermycin A1, novobiocin, gyramide A, or microcin B17.Thus, in this set of compounds the protective activity of Qnr was confined to those that, like quinolones, trap gyrase on DNA in cleaved complexes.

  19. Potency of Traditional Insecticide Materials against Stored Bean ...

    African Journals Online (AJOL)

    Potency of Traditional Insecticide Materials against Stored Bean Weevil, ... AFRICAN JOURNALS ONLINE (AJOL) · Journals · Advanced Search · USING AJOL ... apply traditional insecticide materials in the protection of bean from insect pests.

  20. 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.

  1. Severe pneumococcal pneumonia: impact of new quinolones on prognosis

    Directory of Open Access Journals (Sweden)

    Meybeck Agnes

    2011-03-01

    Full Text Available Abstract Background Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments. Methods Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU, between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4 community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone. Results We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1% died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004, age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01 and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03. Conclusion Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.

  2. Classification of contact allergens according to potency: proposals.

    Science.gov (United States)

    Kimber, I; Basketter, D A; Butler, M; Gamer, A; Garrigue, J-L; Gerberick, G F; Newsome, C; Steiling, W; Vohr, H-W

    2003-12-01

    It is clear that contact allergens vary substantially with regard to the relative potency with which they are able to induce skin sensitisation. Considerations of potency will in the future become a significant factor in the classification of skin sensitising chemicals. It is therefore appropriate to establish what is known of potency and thresholds in the induction of skin sensitisation and the elicitation of allergic contact dermatitis, and to identify approaches that might be available for assessment of relative potency for the purposes of categorising chemical allergens. This paper was prepared by an ECETOC (European Centre for Ecotoxicology and Toxicology) Task Force that had the objective of recommending approaches for the measurement of potency and definition of thresholds for both the induction and elicitation of contact sensitisation. The deliberations recorded here build upon recommendations made previously by an ECETOC Task Force that considered the conduct of standard skin sensitisation test methods for the purposes of hazard identification and risk assessment (ECETOC, Monograph No. 29, Brussels, 2000). The emphasis in this present paper is also on standard and accepted methods for the assessment of skin sensitisation, and for which OECD guidelines are available: the local lymph node assay (LLNA), the guinea pig maximisation test and the occluded patch test of Buehler. For various reasons, discussed in detail herein, attention focused primarily upon consideration of categorisation of chemical allergens and the identification of thresholds with respect to the induction of skin sensitisation, rather than the elicitation of allergic contact dermatitis. It is concluded that although the LLNA is the method of choice for the determination of skin sensitisation potency for the purposes of categorisation, if data are already available from appropriate guinea pig tests then their judicious interpretation may provide information of value in determinations of

  3. Prediction of Quinolone Activity against Mycobacterium avium by Molecular Topology and Virtual Computational Screening

    Science.gov (United States)

    Gozalbes, Rafael; Brun-Pascaud, Monique; García-Domenech, Ramon; Gálvez, Jorge; Girard, Pierre-Marie; Doucet, Jean-Pierre; Derouin, Francis

    2000-01-01

    We conducted a quantitative structure-activity relationship study using a database of 158 quinolones previously tested against Mycobacterium avium-M. intracellulare complex in order to develop a model capable of predicting the activity of new quinolones against the M. avium-M. intracellulare complex in vitro. Topological indices were used as structural descriptors and were related to anti-M. avium-M. intracellulare complex activity by using the linear discriminant analysis (LDA) statistical technique. The discriminant equation thus obtained correctly classified 137 of the 158 quinolones, including 37 of a test group of 44 randomly chosen compounds. This model was then applied to 24 quinolones, including recently developed fluoroquinolones, whose MICs were subsequently determined in vitro by using the Alamar blue microplate assay; the biological results confirmed the model's predictions. The MICs of these 24 quinolones were then treated by multilinear regression (MLR) to establish a model capable of classifying them according to their in vitro activities. Using this model, a good correlation between measured and predicted MICs was found (r2 = 0.88; r2cv [cross-validation correlation] = 0.82). Moxifloxacin, sparfloxacin, and gatifloxacin were the most potent against the M. avium- M. intracellulare complex, with MICs of 0.2, 0.4, and 0.9 μg/ml, respectively. Finally, virtual modifications of these three drugs were evaluated in LDA and MLR models in order to determine the importance of different substituents in their activity. We conclude that the combination of molecular-topology methods, LDA, and MLR provides an excellent tool for the design of new quinolone structures with enhanced activity. PMID:10991858

  4. Characterization of Salmonella Typhimurium DNA gyrase as a target of quinolones.

    Science.gov (United States)

    Kongsoi, Siriporn; Yokoyama, Kazumasa; Suprasert, Apinun; Utrarachkij, Fuangfa; Nakajima, Chie; Suthienkul, Orasa; Suzuki, Yasuhiko

    2015-08-01

    Quinolones exhibit good antibacterial activity against Salmonella spp. isolates and are often the choice of treatment for life-threatening salmonellosis due to multi-drug resistant strains. To assess the properties of quinolones, we performed an in vitro assay to study the antibacterial activities of quinolones against recombinant DNA gyrase. We expressed the S. Typhimurium DNA gyrase A (GyrA) and B (GyrB) subunits in Escherichia coli. GyrA and GyrB were obtained at high purity (>95%) by nickel-nitrilotriacetic acid agarose resin column chromatography as His-tagged 97-kDa and 89-kDa proteins, respectively. Both subunits were shown to reconstitute an ATP-dependent DNA supercoiling activity. Drug concentrations that suppressed DNA supercoiling by 50% (IC50 s) or generated DNA cleavage by 25% (CC25 s) demonstrated that quinolones highly active against S. Typhimurium DNA gyrase share a fluorine atom at C-6. The relationships between the minimum inhibitory concentrations (MICs), IC50 s and CC25 s were assessed by estimating a linear regression between two components. MICs measured against S. Typhimurium NBRC 13245 correlated better with IC50 s (R = 0.9988) than CC25 s (R = 0.9685). These findings suggest that the DNA supercoiling inhibition assay may be a useful screening test to identify quinolones with promising activity against S. Typhimurium. The quinolone structure-activity relationship demonstrated here shows that C-8, the C-7 ring, the C-6 fluorine, and N-1 cyclopropyl substituents are desirable structural features in targeting S. Typhimurium gyrase.

  5. Macrolides vs. quinolones for community-acquired pneumonia: meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Skalsky, K; Yahav, D; Lador, A; Eliakim-Raz, N; Leibovici, L; Paul, M

    2013-04-01

    The relative efficacy, safety and ecological implications of macrolides vs. quinolones in the treatment of community-acquired pneumonia (CAP) are debatable. We performed a systematic review and meta-analysis of randomized controlled trials comparing any macrolide vs. any quinolone for the treatment of CAP among adult inpatients or outpatients, as monotherapy or both in combination with a beta-lactam. We did not limit inclusion by pneumonia severity, publication status, language or date of publication. The primary outcomes assessed were 30-day all-cause mortality and treatment failure. Two authors independently extracted the data. Fixed effect meta-analysis of risk ratios (RRs) with 95% confidence intervals was performed. Sixteen trials (4989 patients) fulfilling inclusion criteria were identified, mostly assessing outpatients with mild to moderate CAP. All-cause mortality was not significantly different for macrolides vs. quinolones, RR 1.03 (0.63-1.68, seven trials), with a low event rate (2%). Treatment failure was significantly lower with quinolones, RR 0.78 (0.67-0.91, 16 trials). The definition of failure used in the primary studies was not clearly representative of patients' benefit. Microbiological failure was lower with quinolones, RR 0.63 (0.49-0.81, 13 trials). All adverse events, adverse events requiring discontinuation and any premature antibiotic discontinuation were significantly more frequent with macrolides, mainly on account of gastrointestinal adverse events. Resistance development was not assessed in the trials. Randomized controlled trials show an advantage of quinolones in the treatment of CAP with regard to clinical cure without need for antibiotic modification at end of treatment and gastrointestinal adverse events. The clinical significance of this advantage is unclear.

  6. Plasmid-mediated quinolone resistance; interactions between human, animal and environmental ecologies

    Directory of Open Access Journals (Sweden)

    Laurent ePOIREL

    2012-02-01

    Full Text Available Resistance to quinolones and fluoroquinolones is being increasingly reported among human but also veterinary isolates during the last two to three decades, very likely as a consequence of the large clinical usage of those antibiotics. Even if the principle mechanisms of resistance to quinolones are chromosome-encoded, due to modifications of molecular targets (DNA gyrase and topoisomerase IV, decreased outer-membrane permeability (porin defect and overexpression of naturally-occurring efflux, the emergence of plasmid-mediated quinolone resistance (PMQR has been reported since 1998. Although these PMQR determinants confer low-level resistance to quinolones and/or fluoroquinolones, they are a favorable background for selection of additional chromosome-encoded quinolone resistance mechanisms. Different transferable mechanisms have been identified, corresponding to the production of Qnr proteins, of the aminoglycoside acetyltransferase AAC(6’-Ib-cr, or of the QepA-type or OqxAB-type efflux pumps. Qnr proteins protect target enzymes (DNA gyrase and type IV topoisomerase from quinolone inhibition (mostly nalidixic acid. The AAC(6’-Ib-cr determinant acetylates several fluoroquinolones, such as norfloxacin and ciprofloxacin. Finally, the QepA and OqxAB efflux pumps extrude fluoroquinolones from the bacterial cell. A series of studies have identified the environment to be a reservoir of PMQR genes, with farm animals and aquatic habitats being significantly involved. In addition, the origin of the qnr genes has been identified, corresponding to the waterborne species Shewanella sp. Altogether, the recent observations suggest that the aquatic environment might constitute the original source of PMQR genes, that would secondly spread among animal or human isolates.

  7. Effect of high-potency cannabis on corpus callosum microstructure.

    Science.gov (United States)

    Rigucci, S; Marques, T R; Di Forti, M; Taylor, H; Dell'Acqua, F; Mondelli, V; Bonaccorso, S; Simmons, A; David, A S; Girardi, P; Pariante, C M; Murray, R M; Dazzan, P

    2016-03-01

    The use of cannabis with higher Δ9-tetrahydrocannabinol content has been associated with greater risk, and earlier onset, of psychosis. However, the effect of cannabis potency on brain morphology has never been explored. Here, we investigated whether cannabis potency and pattern of use are associated with changes in corpus callosum (CC) microstructural organization, in patients with first-episode psychosis (FEP) and individuals without psychosis, cannabis users and non-users. The CC of 56 FEP (37 cannabis users) and 43 individuals without psychosis (22 cannabis users) was virtually dissected and segmented using diffusion tensor imaging tractography. The diffusion index of fractional anisotropy, mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity was calculated for each segment. Across the whole sample, users of high-potency cannabis had higher total CC MD and higher total CC AD than both low-potency users and those who never used (p = 0.005 and p = 0.004, respectively). Daily users also had higher total CC MD and higher total CC AD than both occasional users and those who never used (p = 0.001 and p cannabis is associated with disturbed callosal microstructural organization in individuals with and without psychosis. Since high-potency preparations are now replacing traditional herbal drugs in many European countries, raising awareness about the risks of high-potency cannabis is crucial.

  8. Improving quinolone use in hospitals by using a bundle of interventions in an interrupted time series analysis.

    Science.gov (United States)

    Willemsen, Ina; Cooper, Ben; van Buitenen, Carin; Winters, Marjolein; Andriesse, Gunnar; Kluytmans, Jan

    2010-09-01

    The objectives of the present study were to determine the effects of multiple targeted interventions on the level of use of quinolones and the observed rates of resistance to quinolones in Escherichia coli isolates from hospitalized patients. A bundle consisting of four interventions to improve the use of quinolones was implemented. The outcome was measured from the monthly levels of use of intravenous (i.v.) and oral quinolones and the susceptibility patterns for E. coli isolates from hospitalized patients. Statistical analyses were performed using segmented regression analysis and segmented Poisson regression models. Before the bundle was implemented, the annual use of quinolones was 2.7 defined daily doses (DDDs)/100 patient days. After the interventions, in 2007, this was reduced to 1.7 DDDs/100 patient days. The first intervention, a switch from i.v. to oral medication, was associated with a stepwise reduction in i.v. quinolone use of 71 prescribed daily doses (PDDs) per month (95% confidence interval [CI] = 47 to 95 PDDs/month, P quinolones (reduction, 107 PDDs/month [95% CI = 58 to 156 PDDs/month). Before the interventions the quinolone resistance rate was increasing, on average, by 4.6% (95% CI = 2.6 to 6.1%) per year. This increase leveled off, which was associated with intervention 2 and intervention 4, active monitoring of prescriptions and feedback. Trends in resistance to other antimicrobial agents did not change. This study showed that the hospital-wide use of quinolones can be significantly reduced by an active policy consisting of multiple interventions. There was also a stepwise reduction in the rate of quinolone resistance associated with the bundle of interventions.

  9. Novel application of Wiener vis-à-vis Szeged indices: Antitubercular activities of quinolones

    Indian Academy of Sciences (India)

    Vijay K Agarwal; Shahnaz Bano; Keshav C Mathur; Padmakar V Khadikar

    2000-04-01

    The paper gives a brief account of the recently introduced Szeged index (Sz). Using this index antitubercular activities of N-2,4-difluorophenyl quinolones are subjected to quantitative structure-activity relationship analysis. The potential of Sz related to the Wiener index (W) is critically discussed. In addition, Huckel molecular orbital energies: HOMO, LUMO and total were also used for comparing and modelling antitubercular activities of the quinolones. The results, based on univariate as well as multivariate regressions, have shown that W, Sz and total give better results and that the correlations improve in multivariate regression analyses.

  10. The DNA gyrase-quinolone complex. ATP hydrolysis and the mechanism of DNA cleavage

    DEFF Research Database (Denmark)

    Kampranis, S C; Maxwell, A

    1998-01-01

    Quinolone binding to the gyrase-DNA complex induces a conformational change that results in the blocking of supercoiling. Under these conditions gyrase is still capable of ATP hydrolysis which now proceeds through an alternative pathway involving two different conformations of the enzyme (Kampranis......, S. C., and Maxwell, A. (1998) J. Biol. Chem. 269, 22606-22614). The kinetics of ATP hydrolysis via this pathway have been studied and found to differ from those of the reaction of the drug-free enzyme. The quinolone-characteristic ATPase rate is DNA-dependent and can be induced in the presence...

  11. Prevalence of plasmid-mediated quinolone resistance determinants among oxyiminocephalosporin-resistant Enterobacteriaceae in Argentina

    Directory of Open Access Journals (Sweden)

    Giovanna Rincon Cruz

    2013-11-01

    Full Text Available High quinolone resistance rates were observed among oxyiminocephalosporin-resistant enterobacteria. In the present study, we searched for the prevalence of plasmid-mediated quinolone resistance (PMQR genes within the 55 oxyiminocephalosporin-resistant enterobacteria collected in a previous survey. The main PMQR determinants were aac(6'-Ib-cr and qnrB, which had prevalence rates of 42.4% and 33.3%, respectively. The aac(6'-Ib-cr gene was more frequently found in CTX-M-15-producing isolates, while qnrB was homogeneously distributed among all CTX-M producers.

  12. Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations in quinolone-resistant Escherichia coli isolated from humans and swine in Denmark.

    Science.gov (United States)

    Cavaco, Lina Maria; Frimodt-Møller, Niels; Hasman, Henrik; Guardabassi, Luca; Nielsen, Lene; Aarestrup, Frank Møller

    2008-06-01

    Prevalence of quinolone resistance mechanisms and associations to minimum inhibitory concentrations (MICs) of nalidixic acid (NAL) and ciprofloxacin (CIP) were investigated in 124 Escherichia coli isolated from humans (n=85) and swine (n=39) in Denmark. The collection included 59 high-level CIP-resistant isolates (MIC >or= 4) from human (n=51) and pig origin (n=8) and 65 low-level CIP-resistant isolates (MIC >or= 0.125) from human (n=34) and pig origin (n=31). Resistance by target modification was screened by PCR amplification and sequencing of the quinolone resistance determining regions (QRDRs) of gyrA, gyrB, parC, and parE. QRDR mutations occurred in all except two isolates (98%). All high-level CIP-resistant E. coli had one or two mutations in gyrA in combination with mutations in parC or parE. Mutations in parC and parE were only found in combination with gyrA mutations, and no mutations were observed in gyrB. Efflux pump mechanisms were detected in 10 human (11.8%) and 29 porcine (74.4%) isolates by an efflux pump inhibitor (EPI) agar dilution assay. The aac(6')-Ib-cr gene mediating resistance by enzymatic modification was found in 12 high-level CIP-resistant human isolates. The qnrA and qnrS genes conferring quinolone resistance by target protection were detected in two human low-level CIP-resistant isolates that did not display NAL resistance. As expected, target mutation in QRDRs was the most prevalent mechanism of quinolone resistance. This mechanism was complemented by efflux mechanisms in most porcine isolates. Transferable resistance by target protection or enzymatic modification was less common (10%) and restricted to human isolates.

  13. Nickel-quinolones interaction. Part 5-Biological evaluation of nickel(II) complexes with first-, second- and third-generation quinolones.

    Science.gov (United States)

    Skyrianou, Kalliopi C; Perdih, Franc; Papadopoulos, Athanasios N; Turel, Iztok; Kessissoglou, Dimitris P; Psomas, George

    2011-10-01

    The nickel(II) complexes with the quinolone antibacterial agents oxolinic acid, flumequine, enrofloxacin and sparfloxacin in the presence of the N,N'-donor heterocyclic ligand 2,2'-bipyridylamine have been synthesized and characterized. The quinolones act as bidentate ligands coordinated to Ni(II) ion through the pyridone oxygen and a carboxylato oxygen. The crystal structure of [(2,2'-bipyridylamine)bis(sparfloxacinato)nickel(II)] has been determined by X-ray crystallography. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that they bind to CT DNA with [(2,2'-bipyridylamine)bis(flumequinato)nickel(II)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes have shown that in the presence of CT DNA the complexes can bind to CT DNA by the intercalative binding mode which has also been verified by DNA solution viscosity measurements. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The biological properties of the [Ni(quinolonato)(2)(2,2'-bipyridylamine)] complexes have been evaluated in comparison to the previously reported Ni(II) quinolone complexes [Ni(quinolonato)(2)(H(2)O)(2)], [Ni(quinolonato)(2)(2,2'-bipyridine)] and [Ni(quinolonato)(2)(1,10-phenanthroline)]. The quinolones and their Ni(II) complexes have been tested for their antioxidant and free radical scavenging activity. They have been also tested in vitro for their inhibitory activity against soybean lipoxygenase.

  14. Mechanistic study of electrochemical oxidation of o-dihydroxybenzenes in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone

    Energy Technology Data Exchange (ETDEWEB)

    Moghaddam, Abdolmajid Bayandori [Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1983963113 (Iran, Islamic Republic of)]. E-mail: bayandori@gmail.com; Kobarfard, Farzad [Department of Medicinal Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran 1983963113 (Iran, Islamic Republic of); Fakhari, Ali Reza [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran (Iran, Islamic Republic of); Nematollahi, Davood [Department of Chemistry, Faculty of Science, University of Bu-Ali-Sina, Hamadan (Iran, Islamic Republic of); Davarani, Saied Saeed Hosseiny [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran (Iran, Islamic Republic of)

    2005-11-01

    Electrochemical oxidation of o-dihydroxybenzenes (1a and 1b) has been studied in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone (3) as a nucleophile in aqueous solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the o-quinones derived from o-dihydroxybenzenes (1a and 1b) participate in 1,4-(michael) addition reactions with 3 to form the corresponding new o-dihydroxybenzene derivatives (6a and 6b). We propose a mechanism for the electrode process. The efficient electrochemical synthesis of 6a and 6b has been successfully performed at carbon rod electrodes in an undivided cell in good yield and purity. The products have been characterized after purification by IR, {sup 1}H NMR, {sup 13}C NMR and MS.

  15. Mechanistic study of electrochemical oxidation of catechols in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone

    Energy Technology Data Exchange (ETDEWEB)

    Fakhari, Ali Reza [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran 19835389 (Iran, Islamic Republic of)]. E-mail: a-zavareh@sbu.ac.ir; Nematollahi, Davood [Department of Chemistry, Faculty of Science, University of Bu-Ali-Sina, Hamadan (Iran, Islamic Republic of); Moghaddam, Abdolmajid Bayandori [Department of Chemistry, Faculty of Science, University of Shahid Beheshti, Tehran 19835389 (Iran, Islamic Republic of)

    2005-09-20

    Electrochemical oxidation of catechols (1a-1c) has been studied in the presence of 4-hydroxy-1-methyl-2(1H)-quinolone (3) as a nucleophile in aqueous solution using cyclic voltammetry and controlled-potential coulometry. The results indicate that the quinones derived from catechols (1a-1c) participate in Michael addition reactions with 3 to form the corresponding benzofuran (or isochromeno[4,3-c]quinoline) derivatives (6a-6c). The electrochemical synthesis of (6a-6c) has been successfully performed in an undivided cell in good yield and purity. The oxidation mechanism was deduced from voltammetric data and by coulometry at controlled-potential. The products have been characterized after purification by IR, {sup 1}H NMR, {sup 13}C NMR and MS.

  16. The inactivation of RNase G reduces the Stenotrophomonas maltophilia susceptibility to quinolones by triggering the heat shock response.

    Directory of Open Access Journals (Sweden)

    Alejandra eBernardini

    2015-10-01

    Full Text Available Quinolone resistance is usually due to mutations in the genes encoding bacterial topoisomerases. However different reports have shown that neither clinical quinolone resistant isolates nor in vitro obtained S. maltophilia mutants present mutations in such genes. The mechanisms so far described consist on efflux pumps' overexpression. Our objective is to get information on novel mechanisms of S. maltophilia quinolone resistance. For this purpose, a transposon-insertion mutant library was obtained in S. maltophilia D457.. One mutant presenting reduced susceptibility to nalidixic acid was selected. Inverse PCR showed that the inactivated gene encodes RNase G. Complementation of the mutant with wild-type RNase G allele restored the susceptibility to quinolones. Transcriptomic and real-time RT-PCR analyses showed that several genes encoding heat-shock response proteins were expressed at higher levels in the RNase defective mutant than in the wild-type strain. In agreement with this situation, heat-shock reduces the S. maltophilia susceptibility to quinolone. We can then conclude that the inactivation of the RNase G reduces the susceptibility of S. maltophilia to quinolones, most likely by regulating the expression of heat-shock response genes. Heat-shock induces a transient phenotype of quinolone resistance in S. maltophilia.

  17. Quinolone resistant campylobacter infections in Denmark: risk factors and clinical consequences

    DEFF Research Database (Denmark)

    Engberg, J.; Neimann, J.; Nielsen, E. M.

    2004-01-01

    origin) was associated with a decreased risk. Typing data showed an association between strains from retail food products and broiler chickens and quinolone-sensitive domestically acquired C. jejuni infections. An association between treatment with a fluoroquinolone before stool-specimen collection...

  18. In vitro selection of resistance in haemophilus influenzae by 4 quinolones and 5 beta-lactams.

    Science.gov (United States)

    Clark, Catherine; Kosowska, Klaudia; Bozdogan, Bülent; Credito, Kim; Dewasse, Bonifacio; McGhee, Pamela; Jacobs, Michael R; Appelbaum, Peter C

    2004-05-01

    We tested abilities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, amoxicillin, amoxicillin/clavulanate, cefixime, cefpodoxime, and cefdinir to select resistant mutants in 5 beta-lactamase positive and 5 beta-lactamase negative Haemophilus influenzae strains by single and multistep methodology. In multistep tests, amoxicillin, amoxicillin/clavulanate and cefpodoxime exposure did not cause >4-fold minimum inhibitory concentration (MIC) increase after 50 days. One mutant selected by cefdinir had one amino acid substitution (Gly490Glu) in PBP3 and became resistant to cefdinir. Cefixime exposure caused 8-fold MIC-increase in 1 strain with TEM but the mutant remained cefixime susceptible and had no alteration in PBP3 or TEM. Among 10 strains tested, ciprofloxacin, moxifloxacin, gatifloxacin, levofloxacin caused >4-fold MIC increase in 6, 6, 5, and 2 strain, respectively. Despite the increases in quinolone MICs, none of the mutants became resistant to quinolones by established criteria. Quinolone selected mutants had quindone resistance-determining region (QRDR) alterations in GyrA, GyrB, ParC, ParE. Four quinolone mutants had no QRDR alterations. Among beta-lactams cefdinir and cefixime selected one mutant each with higher MICs however amoxicillin, amoxicillin/clavulanate, and cefpodoxime exposure did not select resistant mutants.

  19. Distinguishing importation from diversification of quinolone-resistant Neisseria gonorrhoeae by molecular evolutionary analysis

    Directory of Open Access Journals (Sweden)

    Dan Michael

    2007-06-01

    Full Text Available Abstract Background Distinguishing the recent introduction of quinolone resistant gonococci into a population from diversification of resistant strains already in the population is important for planning effective infection control strategies. We applied molecular evolutionary analyses to DNA sequences from 9 housekeeping genes and gyrA, parC and porB of 24 quinolone resistant N. gonorrhoeae (QRNG and 24 quinolone sensitive isolates collected in Israel during 2000–2001. Results Phylogenetic and eBURST analyses and estimates of divergence time indicated QRNG were introduced on 3 separate occasions and underwent limited diversification by mutation, deletion and horizontal gene transfer. Reconstruction of N. gonorrhoeae demography showed a slowly declining effective strain population size from 1976 to 1993, rapid decline between 1994 and 1999, and an increase from 1999 to 2001. This is partially attributable to declining gonorrhea case rates from 1973 to 1994. Additional contributing factors are selective sweeps of antibiotic resistant gonococci and increased transmission from sex workers. The abrupt decline in the mid-1990s heralded an increased incidence of gonorrhea from 1997 to the present. The subsequent increase in effective strain population size since 1999 reflects the increased gonococcal census population and introduction of quinolone resistance strains. Conclusion Our study demonstrates the effective use of population genetic approaches to assess recent and historical population dynamics of N. gonorrhoeae.

  20. Quinolone therapy of Klebsiella pneumoniae sepsis following irradiation: Comparison of pefloxacin, ciprofloxacin, and ofloxacin

    Energy Technology Data Exchange (ETDEWEB)

    Brook, I.; Elliott, T.B.; Ledney, G.D. (Armed Forces Radiobiology Research Institute, Bethesda, MD (USA))

    1990-05-01

    Exposure to whole-body irradiation is associated with fatal gram-negative sepsis. The effect of oral therapy with three quinolones, pefloxacin, ciprofloxacin, and ofloxacin, for orally acquired Klebsiella pneumoniae infection was tested in B6D2F1 mice exposed to 8.0 Gy whole-body irradiation from bilaterally positioned 60Co sources. A dose of 10(8) organisms was given orally 2 days after irradiation, and therapy was started 1 day later. Quinolones reduced colonization of the ileum with K. pneumoniae: 16 of 28 (57%) untreated mice harbored the organisms, compared to only 12 of 90 (13%) mice treated with quinolones (P less than 0.005). K. pneumoniae was isolated from the livers of 6 of 28 untreated mice, compared to only 1 of 90 treated mice (P less than 0.001). Only 5 of 20 (25%) untreated mice survived for at least 30 days compared with 17 of 20 (85%) mice treated with ofloxacin, 15 of 20 (75%) mice treated with pefloxacin, and 14 of 20 (70%) treated with ciprofloxacin (P less than 0.05). These data illustrate the efficacy of quinolones for oral therapy of orally acquired K. pneumoniae infection in irradiated hosts.

  1. Quinolone Resistance among Salmonella enterica from Cattle, Broilers and Swine in Denmark

    DEFF Research Database (Denmark)

    Wiuff, C.; Baggesen, Dorte Lau; Madsen, M.

    2000-01-01

    This study was conducted to determine the susceptibility to nalidixic acid and fluoroquinolones of Salmonella Dublin, S. Enteritidis, and S. Typhimurium isolates from cattle, broilers, and pigs over time in Denmark and to characterise the gyrA, gyrB, and parC genes in quinolone-resistant isolates...

  2. Chemistry of Nitroquinolones and Synthetic Application to Unnatural 1-Methyl-2-quinolone Derivatives

    Directory of Open Access Journals (Sweden)

    Nagatoshi Nishiwaki

    2010-07-01

    Full Text Available The 1-methyl-2-quinolone (MeQone framework is often found in alkaloids and recently attention was drawn to unnatural MeQone derivatives with the aim of finding new biologically active compounds, however, low reactivity of the MeQone framework prevents the syntheses of versatile derivatives. A nitro group is one of the useful activating groups for this framework that enables a concise chemical transformation. Among nitroquinolones, 1-methyl-3,6,8-trinitro-2-quinolone (TNQ exhibits unusual reactivity favoring region-selective cine-substitutions that afford 4-substituted 1-methyl-6,8-dinitro-2-quinolones upon treatment with nucleophilic reagents. Contrary to this, 1-methyl-3,6-dinitro-2-quinolone (3,6-DNQ does not undergo any reaction under the same conditions. The unusual reactivity of TNQ is caused by steric repulsion between the methyl group at the 1-position and the nitro group at the 8-position, which distorts the MeQone framework. As a result, the pyridone ring of TNQ loses aromaticity and acts rather as an activated nitroalkene. Indeed, the pyridone moiety of TNQ undergoes cycloaddition with electron-rich alkenes or dienes under mild conditions, whereby a new fused ring is constructed on the [c]-face of the MeQone. Consequently, TNQ can be used as a new scaffold leading to versatile unnatural MeQone derivatives.

  3. Improved microbial screning assay for the detection of quinolone residues in poultry and eggs

    NARCIS (Netherlands)

    Pikkemaat, M.G.; Mulder, P.P.J.; Elferink, J.W.A.; Cocq, A.; Nielen, M.W.F.; Egmond, van H.J.

    2007-01-01

    An improved microbiological screening assay is reported for the detection of quinolone residues in poultry muscle and eggs. The method was validated using fortified tissue samples and is the first microbial assay to effectively detect enrofloxacin, difloxacin, danofloxacin, as well as flumequine and

  4. Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves

    NARCIS (Netherlands)

    Hordijk, J.; Veldman, K.T.; Dierikx, C.M.; Essen-Zandbergen, van A.; Wagenaar, J.A.; Mevius, D.J.

    2012-01-01

    Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional dat

  5. Plasmid-mediated quinolone resistance among non-typhi Salmonella enterica isolates, USA

    Science.gov (United States)

    We determined the prevalence of plasmid-mediated quinolone resistance mechanisms among non-Typhi Salmonella (NTS) spp. isolates from humans, food animals, and retail meat in the United States in 2007. Fifty-one (2.4%) of human isolates (n=2165), 5 (1.6%) of isolates from animal isolates (n=1915) an...

  6. Generation and characterization of quinolone-specific DNA aptamers suitable for water monitoring.

    Science.gov (United States)

    Reinemann, C; Freiin von Fritsch, U; Rudolph, S; Strehlitz, B

    2016-03-15

    Quinolones are antibiotics that are accredited in human and veterinary medicine but are regularly used in high quantities also in industrial livestock farming. Since these compounds are often only incompletely metabolized, significant amounts contaminate the aquatic environment and negatively impact on a variety of different ecosystems. Although there is increasing awareness of problems caused by pharmaceutical pollution, available methods for the detection and elimination of numerous pharmaceutical residues are currently inefficient or expensive. While this also applies to antibiotics that may lead to multi-drug resistance in pathogenic bacteria, aptamer-based technologies potentially offer alternative approaches for sensitive and efficient monitoring of pharmaceutical micropollutants. Using the Capture-SELEX procedure, we here describe the selection of an aptamer pool with enhanced binding qualities for fluoroquinolones, a widely used group of antibiotics in both human and veterinary medicine. The selected aptamers were shown to detect various quinolones with high specificity, while specific binding activities to structurally unrelated drugs were not detectable. The quinolone-specific aptamers bound to ofloxacin, one of the most frequently prescribed fluoroquinolone, with high affinity (KD=0.1-56.9 nM). The functionality of quinolone-specific aptamers in real water samples was demonstrated in local tap water and in effluents of sewage plants. Together, our data suggest that these aptamers may be applicable as molecular receptors in biosensors or as catcher molecules in filter systems for improved monitoring and treatment of polluted water.

  7. [Determination of 25 quinolones in cosmetics by liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Lin, Li; Zhang, Yi; Tu, Xiaoke; Xie, Liqi; Yue, Zhenfeng; Kang, Haining; Wu, Weidong; Luo, Yao

    2015-03-01

    An analytical method was developed for the simultaneous determination of 25 quinolones, including danofloxacin mesylate, enrofloxacin, flumequine, oxloinic acid, ciprofloxacin, sarafloxacin, nalidixic acid, norfloxacin, and ofloxacin etc in cosmetics using direct extraction and liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Cosmetic sample was extracted by acidified acetonitrile, defatted by n-hexane and separated on Poroshell EC-C18 column with gradient elution program using acetonitrile and water (both containing 0. 1% formic acid) as the mobile phases and analyzed by LC-ESI-MS/MS under the positive mode using multiple reaction monitoring (MRM). The interference of matrix was reduced by the matrix-matched calibration standard curve. The method showed good linearities over the range of 1-200 mg/kg for the 25 quinolones with good linear correlation coefficients (r ≥ 0.999). The method detection limit of the 25 quinolones was 1.0 mg/kg, and the recoveries of all analytes in lotion, milky and cream cosmetics matrices ranged from 87.4% to 105% at the spiked levels of 1, 5 and 10 mg/kg with the relative standard deviations (RSD) of 4.54%-19.7% (n = 6). The results indicated that this method is simple, fast and credible, and suitable for the simultaneous determination of the quinolones in the above three types of cosmetics.

  8. Bartonella bacilliformis, endemic pathogen of the Andean region, is intrinsically resistant to quinolones.

    Science.gov (United States)

    del Valle, Luis J; Flores, Lidia; Vargas, Martha; García-de-la-Guarda, Ruth; Quispe, Ruth L; Ibañez, Zoila B; Alvarado, Débora; Ramírez, Pablo; Ruiz, Joaquim

    2010-06-01

    To analyze the sequence of the region involved in the development of quinolone resistance of the gyrA and parC genes in a series of Bartonella bacilliformis isolates recovered prior to the introduction of quinolones, as well as one clinical isolate recovered in the 1970s, establishing the susceptibility levels to nalidixic acid and ciprofloxacin. Five B. bacilliformis were studied: four isolated before 1957, prior to the introduction of quinolones in clinical practice. The remaining strain was isolated in 1977. A fragment of the gyrA and parC genes was amplified and sequenced. Susceptibility to nalidixic acid and ciprofloxacin was established by the E-test method. All the strains were resistant to nalidixic acid (minimum inhibitory concentration (MIC) >256 mg/l). Three isolates presented decreased susceptibility to ciprofloxacin and two were highly resistant (MIC >32 mg/l). All the strains presented an Ala at position 91 of GyrA and position 85 of ParC. B. bacilliformis presents a constitutive resistance to quinolones, which may be related to the presence of Ala at position 91 of GyrA and 85 of ParC. These results advise against the current clinical guidelines recommending the use of ciprofloxacin to treat bartonellosis in some countries of the Andean area. Copyright 2009 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. Prevalence and characteristics of quinolone resistance in Escherichia coli in veal calves

    NARCIS (Netherlands)

    Hordijk, J.; Veldman, K.T.; Dierikx, C.M.; Essen-Zandbergen, van A.; Wagenaar, J.A.; Mevius, D.J.

    2012-01-01

    Quinolone resistance is studied and reported increasingly in isolates from humans, food-producing animals and companion animals. Resistance can be caused by chromosomal mutations in topoisomerase genes, plasmid-mediated resistance genes, and active transport through efflux pumps. Cross sectional dat

  10. [Preliminary study on occurrence and health risk assessment of quinolone antibiotics in vegetables from Guangzhou, China].

    Science.gov (United States)

    Li, Yan-Wen; Zhang, Yan; Mo, Ce-Hui; Tai, Yi-Ping; Wu, Xiao-Lian; Wang, Ji-Yang; Su, Qing-Yun

    2010-10-01

    Quinolone antibiotics (QNs) including norfloxacin (NOR), enrofolxacin (ENR), ciprofloxacin (CIP) and lomefloxacin (LOM) in vegetable samples collected from Guangzhou were determined by high performance liquid chromatography (HPLC) coupled with fluorescent detector (FLD). The detected frequency of QNs was 96% in vegetables. The total concentration of quinolones (sigma QNs) detected in vegetable ranged from 1.0 microg/kg to 1 683.1 microg/kg (F.W.). Leafy vegetable topped the content of quinolones among the three types of vegetables, followed by the melon-fruit vegetable and rhizome vegetable. The detected frequency of the four quinolone antibiotics ranked as NOR > CIP > LOM > ENR. Except ENR, concentrations of CIP, NOR, LOM and sigma QNs in pollution-free vegetable, green vegetable and organic vegetable were higher than those in routine cultivated vegetables. The maximum contribution to ADI value (caculated by the sum of CIP and ENR) is estimated up to 41.5% and 83% for adults and children respectively via consumption of vegetables.

  11. CE determination of quinolones in the presence of bovine serum albumin.

    Science.gov (United States)

    Qin, Weidong; Liu, Qingchun; Fan, Yongxia

    2009-01-01

    This article describes the influence of bovine serum albumin (BSA) as an additive on the capillary electrophoresis-potential gradient determination of five quinolones, enoxacin, norfloxacin, ofloxacin, fleroxacin, and pazufloxacin. With 10 mg/L of BSA present in the buffer of 30 mM Tris and 3 mM phosphoric acid at pH 9, the detection limits of the five quinolones were in the range of 0.24-0.68 mg/L, i. e. 5.8-16.5-fold lower than those obtained with the buffer devoid of BSA, and the analysis time was shortened. We suggest that the inner wall-adsorbed BSA suppresses the adsorption of quinolones and simultaneously enhances the electroosmotic flow rate. Our experiments indicated that adopting the potential gradient detection technique could eliminate the interference of the UV-active proteins on the detection of quinolones that would occur with conventional optical detection, and therefore offer high detection sensitivity. As a demonstration, the method was applied to the determination of QNs in fortified chicken muscle sample with satisfactory results.

  12. Potency determination of antidandruff shampoos in nystatin international unit equivalents

    Directory of Open Access Journals (Sweden)

    Anusha Hewage D.B.G

    2008-01-01

    Full Text Available A convenient standard microbiological potency determination test for the antidandruff shampoos was developed by adopting the pharmacopoeial microbiological assay procedure of the drug nystatin. A standard curve was drawn consisting of the inhibition zone diameters vs. logarithm of nystatin concentrations in international units using the fungus Saccharomyces cerevisiae (yeast strain National Collection of Type Culture (NCTC 1071606 as the test organism. From the standard curve the yeast inhibitory potencies of the shampoos in nystatin international unit equivalents were determined from the respective inhibition zones of the test samples of the shampoos. Under test conditions four shampoo samples showed remarkable fungal inhibitory potencies of 10227, 10731, 12396 and 18211 nystatin international unit equivalents/ml while two shampoo samples had extremely feeble inhibitory potencies 4.07 and 4.37 nystatin international unit equivalents/ml although the latter two products claimed antifungal activity. The potency determination method could be applied to any antidandruff shampoo with any one or a combination of active ingredients.

  13. A series of 2D metal-quinolone complexes: Syntheses, structures, and physical properties

    Energy Technology Data Exchange (ETDEWEB)

    He, Jiang-Hong [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Xiao, Dong-Rong, E-mail: xiaodr98@yahoo.com.cn [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Chen, Hai-Yan; Sun, Dian-Zhen; Yan, Shi-Wei; Wang, Xin; Ye, Zhong-Li [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Luo, Qun-Li, E-mail: qlluo@swu.edu.cn [College of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Wang, En-Bo, E-mail: wangeb889@nenu.edu.cn [Key Laboratory of Polyoxometalate Science of Ministry of Education, Department of Chemistry, Northeast Normal University, Changchun 130024 (China)

    2013-02-15

    Six novel 2D metal-quinolone complexes, namely [Cd(cfH)(bpdc)]{center_dot}H{sub 2}O (1), [M(norfH)(bpdc)]{center_dot}H{sub 2}O (M=Cd (2) and Mn (3)), [Mn{sub 2}(cfH)(odpa)(H{sub 2}O){sub 3}]{center_dot}0.5H{sub 2}O (4), [Co{sub 2}(norfH)(bpta)({mu}{sub 2}-H{sub 2}O)(H{sub 2}O){sub 2}]{center_dot}H{sub 2}O (5) and [Co{sub 3}(saraH){sub 2}(Hbpta){sub 2}(H{sub 2}O){sub 4}]{center_dot}9H{sub 2}O (6) (cfH=ciprofloxacin, norfH=norfloxacin, saraH=sarafloxacin, bpdc=4,4 Prime -biphenyldicarboxylate, odpa=4,4 Prime -oxydiphthalate, bpta=3,3 Prime ,4,4 Prime -biphenyltetracarboxylate) have been synthesized and characterized. Compounds 1-3 consist of 2D arm-shaped layers based on the 1D {l_brace}M(COO){r_brace}{sub n}{sup n+} chains. Compounds 4 and 5 display 2D structures based on tetranuclear manganese or cobalt clusters with (3,6)-connected kgd topology. Compound 6 exhibits a 2D bilayer structure, which represents the first example of metal-quinolone complexes with 2D bilayer structure. By inspection of the structures of 1-6, it is believed that the long aromatic polycarboxylate ligands are important for the formation of 2D metal-quinolone complexes. The magnetic properties of compounds 3-6 was studied, indicating the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compounds 1-2 are discussed. - Graphical abstract: Six novel 2D metal-quinolone complexes have been prepared by self-assemblies of the quinolones and metal salts in the presence of long aromatic polycarboxylates. Highlights: Black-Right-Pointing-Pointer Compounds 1-3 consist of novel 2D arm-shaped layers based on the 1D {l_brace}M(COO){r_brace}{sub n}{sup n+} chains. Black-Right-Pointing-Pointer Compounds 4 and 5 are two novel 2D layers based on tetranuclear Mn or Co clusters with kgd topology. Black-Right-Pointing-Pointer Compound 6 is the first example of metal-quinolone complexes with 2D bilayer structure. Black-Right-Pointing-Pointer Compounds 1-6 represent six unusual

  14. Microbial screening for quinolones residues in cow milk by bio-optical method.

    Science.gov (United States)

    Appicciafuoco, Brunella; Dragone, Roberto; Frazzoli, Chiara; Bolzoni, Giuseppe; Mantovani, Alberto; Ferrini, Anna Maria

    2015-03-15

    The use of antibiotics on lactating cows should be monitored for the possible risk of milk contamination with residues. Accordingly, Maximum Residue Levels (MRLs) are established by the European Commission to guarantee consumers safety. As pointed out by Dec 2002/657/EC, screening is the first step in the strategy for antibiotic residue control, thus playing a key role in the whole control procedure. However, current routine screening methods applied in milk chain still fail to detect residues of quinolones at concentrations of interest. This paper reports the findings of a new bio-optical method for the screening of quinolones residues in bovine milk, based on E. coli ATCC 11303 growth inhibition. The effect of blank and spiked cow milk samples (aliquots equivalents to 0.8%, v/v) is evaluated in Mueller Hinton Broth (MHb) and MHb enriched with MgSO4 2% (MHb-Mg) inoculated with the test strain at the concentration of 10(4)CFU/mL. The presence of quinolones inhibits the cellular growth in MHb, while this effect is neutralized in MHb-Mg allowing both detection and presumptive identification of quinolones. Growth of the test strain is monitored at 37 °C in a Bioscreen C automated system, and Optical Density (OD) at 600 nm is recorded every 10 min after shaking for 10s. Growth curves (OD vs. time) of E. coli ATCC 11303 are assessed in milk samples, with and without quinolones, and their differences in terms of ΔOD (ΔOD600nm=ODMHb-Mg-ODMHb) are calculated. The presence of quinolones is detected by the cellular growth inhibition (OD vs time, none increase in the value OD) and presumptively identified through the increase of the slope of ΔOD600nm curve (ΔOD vs. time), after about 3h of incubation. The detection limit for ciprofloxacin and enrofloxacin is at the level of MRL, for marbofloxacin is at 2-fold the MRL whereas for danofloxacin is at 4-fold the MRL. Although the sensitivity of the method could be further improved and the procedure automated, it is a

  15. Sub-inhibitory concentrations of vancomycin prevent quinolone-resistance in a penicillin-resistant isolate of Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Moreillon Philippe

    2001-07-01

    Full Text Available Abstract Background The continuous spread of penicillin-resistant pneumococci represents a permanent threat in the treatment of pneumococcal infections, especially when strains show additional resistance to quinolones. The main objective of this study was to determine a treatment modality impeding the emergence of quinolone resistance. Results Exposure of a penicillin-resistant pneumococcus to increasing concentrations of trovafloxacin or ciprofloxacin selected for mutants resistant to these drugs. In the presence of sub-inhibitory concentrations of vancomycin, development of trovafloxacin-resistance and high-level ciprofloxacin-resistance were prevented. Conclusions Considering the risk of quinolone-resistance in pneumococci, the observation might be of clinical importance.

  16. Decay mechanisms of protonated 4-quinolone antibiotics after electrospray ionization and ion activation.

    Science.gov (United States)

    Kovačević, Borislav; Schorr, Pascal; Qi, Yulin; Volmer, Dietrich A

    2014-11-01

    This study presents a detailed experimental investigation of charge isomers of protonated 4-quinolone antibiotics molecules formed during electrospray ionization (ESI) with proposed dissociation mechanisms after collisional activation. Piperazinyl quinolones have been previously shown to exhibit erratic behavior during tandem MS analyses of biological samples, which originated from varying ratios of two isomeric variants formed during ESI. Here, a combination of ESI-collision-induced dissociation (CID), differential ion mobility spectrometry (DMS), high resolution MS, and density functional theory (DFT) was used to investigate the underlying mechanisms of isomer formation and their individual dissociation behaviors. The study focused on ciprofloxacin; major findings were confirmed using structurally related 4-quinolones. DFT calculations showed a reversal of basicity for piperazinyl quinolones between liquid and gas phase. We provide an experimental comparison and theoretical treatment of factors influencing the formation ratio of the charge isomers during ESI, including solvent pH, protic/aprotic nature of solvent, and structural effects such as pK a and proton affinity. The actual dissociation mechanisms of the isomers of the protonated molecules were studied by separating the individual isomers via DMS-MS, which allowed type-specific CID spectra to be recorded. Both primary CID reactions of the two charge isomers originated from the same carboxyl group by charge-remote (CO(2) loss) and charge-mediated (H(2)O loss) fragmentation of the piperazinyl quinolones, depending on whether the proton resides on the more basic keto or the piperazinyl group, followed by a number of secondary dissociation reactions. The proposed mechanisms were supported by calculated energies of precursors, transition states, and products for competing pathways.

  17. Detection of quinolones in poultry meat obtained from retail centers in Santiago Province, the Dominican Republic.

    Science.gov (United States)

    Silfrany, R O; Caba, R E; Solís de Los Santos, F; Hanning, I

    2013-02-01

    In the Dominican Republic, poultry consumption per capita is greater than 34 kg of poultry meat per year. However, antibiotics, specifically the quinolone group, may be overused and can result in residues in the poultry meat. These residues are of concern because consumers may have allergies to antibiotics and antibiotic-resistant bacteria can develop from overuse of antibiotics in production. Little is known concerning this issue specifically for Santiago Province in the Dominican Republic. Thus, the main purpose of this research was to evaluate the incidence of residual quinolones in poultry meat and determine whether any residues detected were higher than the residue maximum limits (100 μg/kg) established by food industry authorities, including the U.S. Food and Drug Administration and European Food Safety Authority. A total of 135 samples of chicken breast were taken from different retail meat centers in the nine municipalities of Santiago Province (Santiago, Tamboril, Sabana Iglesia, Villa Bisonó, Puñal, Villa González, Licey, Jánico, and San José De Las Matas) and were analyzed using the Equinox test (Immunotec, Swanton, VT). Of the 135 samples analyzed, 50% from Sabana Iglesia, 20% from Licey, 20% from San Jose De Las Matas, and 6.25% from Santiago contained residues of quinolones higher than the residue maximum limits. No quinolone residues were detected in samples obtained from Janico, Punal, Tamboril, Villa Bisono, or Villa Gonzalez. The results of this investigation suggest that some poultry meat sold for human consumption in Santiago Province of the Dominican Republic contains quinolone residues and may represent a health risk to some consumers.

  18. Standardization and validation of Vero cell assay for potency estimation of diphtheria antitoxin serum.

    Science.gov (United States)

    Kumar, Sunil; Kanwar, Sarika; Bansal, Vivek; Sehgal, Rakesh

    2009-10-01

    Diphtheria toxin has the capacity to block protein synthesis in cultured mammalian cells, and thus causing cell death. This capacity of diphtheria toxin was utilized for in-vitro neutralization test to determine antibody titer, using Vero cells, which have been found to be susceptible to diphtheria toxin. In the present study, a Vero cell assay was standardized and validated for potency estimation of diphtheria antitoxin serum (DATS). The results obtained by Vero cell assay were compared with in-vivo biological assay. High degree of correlation (+0.98) was found between in-vivo biological assay and in-vitro Vero cell assay. The assay has also been found to be effective in determining the rising antibody titer in the equines inducted in DATS production. The present study indicated that although biological assays hold the key for final potency estimations till date but in the future scenario in-vitro Vero cell assay may be a good alternative to in-vivo biological assay.

  19. 喹诺酮类药物的研究进展%Progress on the Research of Pharmaceuticals of Quinolones

    Institute of Scientific and Technical Information of China (English)

    曾焕君; 王怀生

    2014-01-01

    Quinolones are synthetic antibacterial agents. many quinolones have one or two chiral centers and some of enantiomers show dif erent feature in pharmacology, toxicology and pharmacodynamics. In this paper, chiral separation and determination of quinolones about recent years were reviewed for providing some reference in the research of quinolones.%喹诺酮类药物是人工合成的抗菌药,很多药物都具有1~2个手性中心,且有些对映体呈现不同的药理学的、毒理学的、药效学的特性。本文对近几年喹诺酮类的药物手性的拆分与定量进行了研究,为临床上研究喹诺酮类的药物提供了一系列参考依据。

  20. Mutagenic Potency of Food-Derived Heterocyclic Amines

    Energy Technology Data Exchange (ETDEWEB)

    Felton, J S; Knize, M G; Wu, R W; Colvin, M E; Hatch, F T; Malfatti, M A

    2006-10-26

    The understanding of mutagenic potency has been primarily approached using ''quantitative structure activity relationships'' (QSAR). Often this method allows the prediction of mutagenic potency of the compound based on its structure. But it does not give the underlying reason why the mutagenic activities differ. We have taken a set of heterocyclic amine structures and used molecular dynamic calculations to dock these molecules into the active site of a computational model of the cytochrome P-450 1A1 enzyme. The calculated binding strength using Boltzman distribution constants was then compared to the QSAR value (HF/6-31G* optimized structures) and the Ames/Salmonella mutagenic potency. Further understanding will only come from knowing the complete set of mutagenic determinants. These include the nitrenium ion half-life, DNA adduct half-life, efficiency of repair of the adduct, and ultimately fixation of the mutation through cellular processes. For two isomers, PhIP and 3-Me-PhIP, we showed that for the 100-fold difference in the mutagenic potency a 5-fold difference can be accounted for by differences in the P450 oxidation. The other factor of 20 is not clearly understood but is downstream from the oxidation step. The application of QSAR (chemical characteristics) to biological principles related to mutagenesis is explored in this report.

  1. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions....

  2. Prevalence of plasmid-mediated quinolone resistance determinants in Enterobacteriaceae strains isolated in North-East Italy.

    Science.gov (United States)

    Kocsis, B; Mazzariol, A; Kocsis, E; Koncan, R; Fontana, R; Cornaglia, G

    2013-02-01

    We investigated the prevalence of plasmid-mediated quinolone resistance genes in 756 clinical isolates of Enterobacteriaceae originating from Microbiology Diagnostic Laboratories of North-East Italy. Five point zero two percent of isolates carried a qnr determinant while the aac(6')-Ib-cr determinant was detected in 9·25% of isolates. We also investigated the association between the plasmid-mediated quinolone resistance and the beta-lactamase genes, and characterized the plasmids carrying these determinants of resistance.

  3. Impact of the E540V amino acid substitution in GyrB of Mycobacterium tuberculosis on quinolone resistance.

    Science.gov (United States)

    Kim, Hyun; Nakajima, Chie; Yokoyama, Kazumasa; Rahim, Zeaur; Kim, Youn Uck; Oguri, Hiroki; Suzuki, Yasuhiko

    2011-08-01

    Amino acid substitutions conferring resistance to quinolones in Mycobacterium tuberculosis have generally been found within the quinolone resistance-determining regions (QRDRs) in the A subunit of DNA gyrase (GyrA) rather than the B subunit of DNA gyrase (GyrB). To clarify the contribution of an amino acid substitution, E540V, in GyrB to quinolone resistance in M. tuberculosis, we expressed recombinant DNA gyrases in Escherichia coli and characterized them in vitro. Wild-type and GyrB-E540V DNA gyrases were reconstituted in vitro by mixing recombinant GyrA and GyrB. Correlation between the amino acid substitution and quinolone resistance was assessed by the ATP-dependent DNA supercoiling assay, quinolone-inhibited supercoiling assay, and DNA cleavage assay. The 50% inhibitory concentrations of eight quinolones against DNA gyrases bearing the E540V amino acid substitution in GyrB were 2.5- to 36-fold higher than those against the wild-type enzyme. Similarly, the 25% maximum DNA cleavage concentrations were 1.5- to 14-fold higher for the E540V gyrase than for the wild-type enzyme. We further demonstrated that the E540V amino acid substitution influenced the interaction between DNA gyrase and the substituent(s) at R-7, R-8, or both in quinolone structures. This is the first detailed study of the contribution of the E540V amino acid substitution in GyrB to quinolone resistance in M. tuberculosis.

  4. Membrane Distribution of the Pseudomonas Quinolone Signal Modulates Outer Membrane Vesicle Production in Pseudomonas aeruginosa.

    Science.gov (United States)

    Florez, Catalina; Raab, Julie E; Cooke, Adam C; Schertzer, Jeffrey W

    2017-08-08

    The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule in Pseudomonas aeruginosa that also mediates its own packaging and transport by stimulating outer membrane vesicle (OMV) formation. Because OMVs have been implicated in many virulence-associated behaviors, it is critical that we understand how they are formed. Our group proposed the bilayer-couple model for OMV biogenesis, where PQS intercalates into the outer membrane, causing expansion of the outer leaflet and consequently inducing curvature. In accordance with the model, we hypothesized that PQS must be transported from the cytoplasm to the outer membrane before it can initiate OMV formation. We initially examined two laboratory strains of P. aeruginosa and found significant strain-dependent differences. PQS export correlated strongly with OMV production, even though equivalent amounts of total PQS were produced by both strains. Interestingly, we discovered that poor OMV producers sequestered the majority of PQS in the inner membrane, which appeared to be the result of early saturation of the export pathway. Further analysis showed that strain-specific PQS export and OMV biogenesis patterns were stable once established but could be significantly altered by changing the growth medium. Finally, we demonstrated that the associations described for laboratory strains also held for three clinical strains. These results suggest that factors controlling the export of PQS dictate OMV biogenesis. This work provides new insight into PQS-controlled virulence in P. aeruginosa and provides important tools to further study signal export and OMV biogenesis.IMPORTANCE Bacterial secretion has been recognized as an essential facet of microbial pathogenesis and human disease. Numerous virulence factors have been found to be transported within outer membrane vesicles (OMVs), and delivery using these biological nanoparticles often results in increased potency. OMV biogenesis is an important but poorly

  5. Prevalence of quinolone resistance determinants in non-typhoidal Salmonella isolates from human origin in Extremadura, Spain.

    Science.gov (United States)

    Campos, Maria Jorge; Palomo, Gonzalo; Hormeño, Lorena; Herrera-León, Silvia; Domínguez, Lucas; Vadillo, Santiago; Píriz, Segundo; Quesada, Alberto

    2014-05-01

    Resistance to the quinolones nalidixic acid (NAL) and ciprofloxacin (CIP) and the occurrence of quinolone resistance determinants have been investigated in 300 non-typhoidal Salmonella from human origin, isolated in the years between 2004 and 2008, in 6 hospitals within Extremadura (Spain). Salmonella Enteritidis was the major serotype found among quinolone-resistant isolates, most of which were clustered by clonal analysis to a single clone, which presented D87 or S83 substitutions in GyrA. Eleven isolates presented the non-classical quinolone resistance phenotype (resistance to CIP and susceptibility to NAL), lacking mutations in the quinolone resistance determinant region of topoisomerase genes. Among them, one Salmonella Typhimurium isolate carried a qnrS1 gene in a low-molecular-weight plasmid, pQnrS1-HLR25, identical to plasmids previously found in the UK, Taiwan, and USA. The occurrence of this genetic element could represent a risk for the horizontal transmission of quinolone resistance among Enterobacteriaceae in the Iberian Peninsula.

  6. Comparative Analysis of Quinolone Resistance in Clinical Isolates of Klebsiella pneumoniae and Escherichia coli from Chinese Children and Adults

    Directory of Open Access Journals (Sweden)

    Ying Huang

    2015-01-01

    Full Text Available The objective of this study was to compare quinolone resistance and gyrA mutations in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese adults who used quinolone in the preceding month and children without any known history of quinolone administration. The antimicrobial susceptibilities of 61 isolates from children and 79 isolates from adults were determined. The mutations in the quinolone resistance-determining regions in gyrA gene were detected by PCR and DNA sequencing. Fluoroquinolone resistance and types of gyrA mutations in isolates from children and adults were compared and statistically analyzed. No significant differences were detected in the resistance rates of ciprofloxacin and levofloxacin between children and adults among isolates of the two species (all P>0.05. The double mutation Ser83→Leu + Asp87→Asn in the ciprofloxacin-resistant isolates occurred in 73.7% isolates from the children and 67.9% from the adults, respectively (P=0.5444. Children with no known history of quinolone administration were found to carry fluoroquinolone-resistant Enterobacteriaceae isolates. The occurrence of ciprofloxacin resistance and the major types of gyrA mutations in the isolates from the children were similar to those from adults. The results indicate that precautions should be taken on environmental issues resulting from widespread transmission of quinolone resistance.

  7. Genotoxicity of quinolones: substituents contribution and transformation products QSAR evaluation using 2D and 3D models.

    Science.gov (United States)

    Li, Min; Wei, Dongbin; Zhao, Huimin; Du, Yuguo

    2014-01-01

    The genotoxicity of 21 quinolones antibiotics was determined using SOS/umu assay. Some quinolones exhibited high genotoxicity, and the chemical substituent on quinolone ring significantly affected genotoxicity. To establish the relationship between genotoxicity and substituent, a 2D-QSAR model based on quantum chemical parameters was developed. Calculation suggested that both steric and electrostatic properties were correlated well with genotoxicity. Furthermore, the specific effect on three key active sites (1-, 7- and 8-positions) of quinolone ring was investigated using a 3D-QSAR (comparative molecular field analysis, CoMFA) method. From our modeling, the genotoxicity increased when substituents had: (1) big volume and/or positive charge at 1-position; (2) negative charge at 7-position; and (3) small volume and/or negative charge at 8-position. The developed QSAR models were applicable to estimate genotoxicity of quinolones antibiotics and their transformation products. It is noted that some of the transformation products exhibited higher genotoxicity comparing to their precursor (e.g., ciprofloxacin). This study provided an alternative way to understand the molecule genotoxicity of quinolones derivatives, as well as to evaluate their potential environmental risks.

  8. Comparative analysis of quinolone resistance in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese children and adults.

    Science.gov (United States)

    Huang, Ying; Ogutu, James O; Gu, Jiarui; Ding, Fengshu; You, Yuhong; Huo, Yan; Zhao, Hong; Li, Wenjing; Zhang, Zhiwei; Zhang, Wenli; Chen, Xiaobei; Fu, Yingmei; Zhang, Fengmin

    2015-01-01

    The objective of this study was to compare quinolone resistance and gyrA mutations in clinical isolates of Klebsiella pneumoniae and Escherichia coli from Chinese adults who used quinolone in the preceding month and children without any known history of quinolone administration. The antimicrobial susceptibilities of 61 isolates from children and 79 isolates from adults were determined. The mutations in the quinolone resistance-determining regions in gyrA gene were detected by PCR and DNA sequencing. Fluoroquinolone resistance and types of gyrA mutations in isolates from children and adults were compared and statistically analyzed. No significant differences were detected in the resistance rates of ciprofloxacin and levofloxacin between children and adults among isolates of the two species (all P > 0.05). The double mutation Ser83→Leu + Asp87→Asn in the ciprofloxacin-resistant isolates occurred in 73.7% isolates from the children and 67.9% from the adults, respectively (P = 0.5444). Children with no known history of quinolone administration were found to carry fluoroquinolone-resistant Enterobacteriaceae isolates. The occurrence of ciprofloxacin resistance and the major types of gyrA mutations in the isolates from the children were similar to those from adults. The results indicate that precautions should be taken on environmental issues resulting from widespread transmission of quinolone resistance.

  9. Plasmid-related quinolone resistance determinants in epidemic Vibrio parahaemolyticus, uropathogenic Escherichia coli, and marine bacteria from an aquaculture area in Chile.

    Science.gov (United States)

    Aedo, Sandra; Ivanova, Larisa; Tomova, Alexandra; Cabello, Felipe C

    2014-08-01

    Marine bacteria from aquaculture areas with industrial use of quinolones have the potential to pass quinolone resistance genes to animal and human pathogens. The VPA0095 gene, related to the quinolone resistance determinant qnrA, from clinical isolates of epidemic Vibrio parahaemolyticus conferred reduced susceptibility to quinolone after cloning into Escherichia coli K-12 either when acting alone or synergistically with DNA gyrase mutations. In addition, a plasmid-mediated quinolone resistance gene from marine bacteria, aac(6')-Ib-cr, was identical to aac(6')-Ib-cr from urinary tract isolates of E. coli, suggesting a recent flow of this gene between these bacteria isolated from different environments. aac(6')-Ib-cr from E. coli also conferred reduced susceptibility to quinolone and kanamycin when cloned into E. coli K-12.

  10. Survey of Tetracyclines, Sulfonamides, Sulfamethazine, and Quinolones in UHT Milk in China Market

    Institute of Scientific and Technical Information of China (English)

    HAN Rong-wei; ZHENG Nan; WANG Jia-qi; ZHEN Yun-peng; LI Song-li; YU Qun-li

    2013-01-01

    This study surveyed 180 samples of ultra high temperature (UHT) milk of four top Chinese dairy brands collected in the 25 cities in China in June 2011, and assessed their contamination with antibiotics, using the ELISA method. The percentages of tetracyclines, sulfonamides, sulfamethazine, and quinolones detected in the samples were 0, 16.7, 40.6, and 100%, respectively. The maximum concentrations of the tetracyclines, sulfonamides, sulfamethazine and quinolones in UHT milk samples were<1.5, 26.2, 22.6, and 58.8μg kg-1, respectively. None of the samples exceeded the maximum residue levels (MRLs) for these four veterinary drugs, according to the regulations set by China, the European Union (EU) and the Codex Alimentarius Commission (CAC).

  11. An outbreak of multidrug-resistant, quinolone-resistant Salmonella enterica serotype typhimurium DT104

    DEFF Research Database (Denmark)

    Molbak, K.; Baggesen, Dorte Lau; Aarestrup, Frank Møller

    1999-01-01

    , and tetracycline. An increasing proportion of DT104 isolates also have reduced susceptibility to fluoroquinolones. Methods The Danish salmonella surveillance program determines the phage types of all typhimurium strains from the food chain, and in the case of suspected outbreaks, five-drug-resistant strains...... findings here. Results Until 1997, DT104 infections made up less than 1 percent of all human salmonella infections. The strain isolated from patients in the first community outbreak of DT104 in Denmark, in 1998, was resistant to nalidixic acid and had reduced susceptibility to fluoroquinolones...... with fluoroquinolones. Conclusions Our investigation of an outbreak of DT104 documented the spread of quinolone-resistant bacteria from food animals to humans; this spread was associated with infections that were difficult to treat. Because of the increase in quinolone resistance in salmonella, the use...

  12. Resistance to quinolones in Campylobacter jejuni and Campylobacter coli from Danish broilers at farm level

    DEFF Research Database (Denmark)

    Pedersen, Karl; Wedderkopp, A.

    2003-01-01

    Aims : To investigate the prevalence of quinolone resistance among Campylobacter jejuni and Camp. coli isolates from Danish poultry at the farm level, as well as for the whole country. Methods and Results : Data and isolates were collected from a national surveillance of Campylobacter in poultry......-resistant variant. Conclusions : Overall, quinolone resistance among Campylobacter isolates from Danish broilers was 7.5% in 1998 and 1999; it was higher among Camp. coli than Camp. jejuni . Genetic diversity among resistant isolates was lower than among susceptible isolates, and certain clones existed in both...... a resistant and a susceptible variant. Some resistant clones appeared to persist on the farms and were repeatedly isolated from poultry flocks. Significance and Impact of the Study : The study is important for the understanding of persistence and dynamics of Campylobacter in broiler houses. It also highlights...

  13. Determination of fluorinated quinolone antibacterials by ion chromatography with fluorescence detection

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yan-zhen; ZHANG Zheng-yi; ZHOU Yan-chun; LIU Li; ZHU Yan

    2007-01-01

    For preparing fluorinated quinolone antibiotic medicine locally used in stomatology, simultaneous determination of norfloxacin, ciprofloxacin, and enoxacin was carried out by multiphase ion chromatography with fluorescence detection. Quinolone antibiotics were separated by Dionex OmniPac PAX-500 column with an eluent of 15 mmol/L H2SO4 and 35% methanol (v/v) at a flow-rate of 1.0 ml/min and detected with fluorescence with excitation and emission wave lengths of 347 nm and 420 nm respectively. The detection limits (S/N=3) ofnorfloxacin, ciprofloxacin and enoxacin were 50, 105 and 80 ng/ml respectively. The relative standard deviations of retention time, peak area and peak height were less than 1.1% and good linear relationship resulted.The developed method was applied to pharmaceutical formulations and biological fluids.

  14. Origins of the Quinolone Class of Antibacterials: An Expanded "Discovery Story".

    Science.gov (United States)

    Bisacchi, Gregory S

    2015-06-25

    Published descriptions of the specific lines of research leading to the discovery of therapeutically important medicines, especially major new class medicines, have long provided value to the biopharmaceutical community as models of success, often influencing the strategies and methods of subsequent drug research. Quinolone antibacterials represent one of medicine's most important classes of anti-infective agents; yet in contrast to many other classes of anti-infectives, astonishingly few details concerning the origin of the class or the rationale leading to the selection of the first clinical agent, nalidixic acid, were ever published by the discoverers. Moreover, earlier disclosures of an independent discovery of the quinolone class of antibacterials have been almost entirely overlooked by the scientific literature. This review brings together all the available information from primary literature sources relating to both discoveries and provides for the first time a much fuller, if still partially speculative, story of the earliest years of this important class of drugs.

  15. 4(1H)-Quinolones with liver stage activity against Plasmodium berghei.

    Science.gov (United States)

    Lacrue, Alexis N; Sáenz, Fabián E; Cross, R Matthew; Udenze, Kenneth O; Monastyrskyi, Andrii; Stein, Steven; Mutka, Tina S; Manetsch, Roman; Kyle, Dennis E

    2013-01-01

    With the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenic Plasmodium berghei parasite (1052Cl1; PbGFP-Luc(con)) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activity in vitro and causal prophylactic activity in vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.

  16. Occurrence of quinolone- and beta-lactam-resistant Escherichia coli in danish broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne

    ). In Denmark, antimicrobial resistance is annually monitored in both clinical and indicator E. coli isolated from poultry (DANMAP, 2006). However, very little is known on the prevalence of resistance at the flock level. The aim of this study was to determine the prevalence of flocks positive for E. coli...... resistant to quinolones or ß-lactams. Sock samples were collected from 10 broiler parent flocks and 10 broiler offspring flocks. Five pairs of socks were collected from each house. Samples were enriched in McConkey broth and streaked on McConkey agar added with nalidixic acid (32 µg/ml), ciprofloxacin (2 µg...... and nalidixic acid resistances were detected in all flocks. The numbers of E. coli resistant to these drugs were higher in plates from parent flocks than in those from offspring flocks. A broiler parent flock without any history of quinolone usage tested positive for ciprofloxacin-resistant E. coli, although...

  17. Dynamics of quinolone resistance in fecal Escherichia coli of finishing pigs after ciprofloxacin administration.

    Science.gov (United States)

    Huang, Kang; Xu, Chang-Wen; Zeng, Bo; Xia, Qing-Qing; Zhang, An-Yun; Lei, Chang-Wei; Guan, Zhong-Bin; Cheng, Han; Wang, Hong-Ning

    2014-09-01

    Escherichia coli resistance to quinolones has now become a serious issue in large-scale pig farms of China. It is necessary to study the dynamics of quinolone resistance in fecal Escherichia coli of pigs after antimicrobial administration. Here, we present the hypothesis that the emergence of resistance in pigs requires drug accumulation for 7 days or more. To test this hypothesis, 26 pigs (90 days old, about 30 kg) not fed any antimicrobial after weaning were selected and divided into 2 equal groups: the experimental (EP) group and control (CP) group. Pigs in the EP group were orally treated daily with 5 mg ciprofloxacin/kg of body weight for 30 days, and pigs in the CP group were fed a normal diet. Fresh feces were collected at 16 time points from day 0 to day 61. At each time point, ten E. coli clones were tested for susceptibility to quinolones and mutations of gyrA and parC. The results showed that the minimal inhibitory concentration (MIC) for ciprofloxacin increased 16-fold compared with the initial MIC (0.5 µg/ml) after ciprofloxacin administration for 3 days and decreased 256-fold compared with the initial MIC (0.5 µg/ml) after ciprofloxacin withdrawal for 26 days. GyrA (S83L, D87N/ D87Y) and parC (S80I) substitutions were observed in all quinolone-resistant E. coli (QREC) clones with an MIC ≥8 µg/ml. This study provides scientific theoretical guidance for the rational use of antimicrobials and the control of bacterial resistance.

  18. Characterization of quinolone resistance in Salmonella spp. isolates from food products and human samples in Brazil

    Science.gov (United States)

    Pribul, Bruno Rocha; Festivo, Marcia Lima; de Souza, Miliane Moreira Soares; dos Prazeres Rodrigues, Dalia

    2016-01-01

    Non-typhoidal salmonellosis is an important zoonotic disease caused by Salmonella enterica. The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. A total of 129 NTS isolates (samples from human origin, food from animal origin, environmental, and animal) grouped as from animal (n = 62) and human (n = 67) food were evaluated between 2009 and 2013. These isolates were investigated through serotyping, antimicrobial susceptibility testing, and the presence of plasmid-mediated quinolone resistance (PMQR) genes (qnr, aac(6′)-Ib) and associated integron genes (integrase, and conserved integron region). Resistance to quinolones and/or fluoroquinolones, from first to third generations, was observed. Fifteen isolates were positive for the presence of qnr genes (8 qnrS, 6 qnrB, and 1 qnrD) and twenty three of aac(6′)-Ib. The conserved integron region was detected in 67 isolates as variable regions, from ±600 to >1000 pb. The spread of NTS involving PMQR carriers is of serious concern and should be carefully monitored. PMID:26887245

  19. Cellular Response to Ciprofloxacin in Low-Level Quinolone-Resistant Escherichia coli

    Directory of Open Access Journals (Sweden)

    Jesús Machuca

    2017-07-01

    Full Text Available Bactericidal activity of quinolones has been related to a combination of DNA fragmentation, reactive oxygen species (ROS production and programmed cell death (PCD systems. The underlying molecular systems responsible for reducing bactericidal effect during antimicrobial therapy in low-level quinolone resistance (LLQR phenotypes need to be clarified. To do this and also define possible new antimicrobial targets, the transcriptome profile of isogenic Escherichia coli harboring quinolone resistance mechanisms in the presence of a clinical relevant concentration of ciprofloxacin was evaluated. A marked differential response to ciprofloxacin of either up- or downregulation was observed in LLQR strains. Multiple genes implicated in ROS modulation (related to the TCA cycle, aerobic respiration and detoxification systems were upregulated (sdhC up to 63.5-fold in mutants with LLQR. SOS system components were downregulated (recA up to 30.7-fold. yihE, a protective kinase coding for PCD, was also upregulated (up to 5.2-fold. SdhC inhibition sensitized LLQR phenotypes (up to ΔLog = 2.3 after 24 h. At clinically relevant concentrations of ciprofloxacin, gene expression patterns in critical systems to bacterial survival and mutant development were significantly modified in LLQR phenotypes. Chemical inhibition of SdhC (succinate dehydrogenase validated modulation of ROS as an interesting target for bacterial sensitization.

  20. Characterization of quinolone resistance in Salmonella spp. isolates from food products and human samples in Brazil.

    Science.gov (United States)

    Pribul, Bruno Rocha; Festivo, Marcia Lima; de Souza, Miliane Moreira Soares; Rodrigues, Dalia dos Prazeres

    2016-01-01

    Non-typhoidal salmonellosis is an important zoonotic disease caused by Salmonella enterica. The aim of this study was to investigate the prevalence of plasmid-mediated quinolone resistance in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. A total of 129 NTS isolates (samples from human origin, food from animal origin, environmental, and animal) grouped as from animal (n=62) and human (n=67) food were evaluated between 2009 and 2013. These isolates were investigated through serotyping, antimicrobial susceptibility testing, and the presence of plasmid-mediated quinolone resistance (PMQR) genes (qnr, aac(6')-Ib) and associated integron genes (integrase, and conserved integron region). Resistance to quinolones and/or fluoroquinolones, from first to third generations, was observed. Fifteen isolates were positive for the presence of qnr genes (8 qnrS, 6 qnrB, and 1 qnrD) and twenty three of aac(6')-Ib. The conserved integron region was detected in 67 isolates as variable regions, from ±600 to >1000pb. The spread of NTS involving PMQR carriers is of serious concern and should be carefully monitored.

  1. A series of 2D metal-quinolone complexes: Syntheses, structures, and physical properties

    Science.gov (United States)

    He, Jiang-Hong; Xiao, Dong-Rong; Chen, Hai-Yan; Sun, Dian-Zhen; Yan, Shi-Wei; Wang, Xin; Ye, Zhong-Li; Luo, Qun-Li; Wang, En-Bo

    2013-02-01

    Six novel 2D metal-quinolone complexes, namely [Cd(cfH)(bpdc)]rad H2O (1), [M(norfH)(bpdc)]rad H2O (M=Cd (2) and Mn (3)), [Mn2(cfH)(odpa)(H2O)3]rad 0.5H2O (4), [Co2(norfH)(bpta)(μ2-H2O)(H2O)2]rad H2O (5) and [Co3(saraH)2(Hbpta)2(H2O)4]rad 9H2O (6) (cfH=ciprofloxacin, norfH=norfloxacin, saraH=sarafloxacin, bpdc=4,4'-biphenyldicarboxylate, odpa=4,4'-oxydiphthalate, bpta=3,3',4,4'-biphenyltetracarboxylate) have been synthesized and characterized. Compounds 1-3 consist of 2D arm-shaped layers based on the 1D {M(COO)}nn+ chains. Compounds 4 and 5 display 2D structures based on tetranuclear manganese or cobalt clusters with (3,6)-connected kgd topology. Compound 6 exhibits a 2D bilayer structure, which represents the first example of metal-quinolone complexes with 2D bilayer structure. By inspection of the structures of 1-6, it is believed that the long aromatic polycarboxylate ligands are important for the formation of 2D metal-quinolone complexes. The magnetic properties of compounds 3-6 was studied, indicating the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compounds 1-2 are discussed.

  2. 喹诺酮类药物的研究进展%Research Progress of Quinolones

    Institute of Scientific and Technical Information of China (English)

    田秋月

    2014-01-01

    喹诺酮类药物是一类人工合成的抗菌药物,目前广泛应用于临床抗感染治疗中,具有较强的抗菌活性。本文主要从喹诺酮类药物的作用机制、临床应用、不良反应及耐药机制等方面进行分析和整理,综述其研究进展并对其未来的研究方向提出了建议,希望为今后喹诺酮药物的研究提供一定的参考依据。%Quinolones are a group of synthetic antibacteril drugs with strong antibacterial activity which have a broad range of clinic applications in recent years. In this article, research progress of quinolones was analyzed and summarized from the aspects of action mechanism, clinical application, adverse reactions and drug resistance mechanism, and the future research direction of quinolones was proposed.

  3. Liquid chromatographic determination of quinolones in water and human urine samples after microextraction by packed sorbent.

    Science.gov (United States)

    Rani, Susheela; Kumar, Ashwini; Malik, Ashok Kumar; Singh, Baldev

    2012-01-01

    A method for the simultaneous determination of quinolones in water and urine samples by microextraction in a sorbent-packed syringe (MEPS) with LC is described. MEPS is a new miniaturized SPE technique that can be used with chromatographic instruments without any modifications. In MEPS, approximately 1 mg of the solid packing material is inserted into a syringe (100-250 microL) as a plug. Sample preparation takes place on the packed bed. The new method is promising, easy to use, economical, and rapid. The determination of quinolones in groundwater and urine was performed using MEPS as a sample preparation method with LC-UV determination. Four quinolone antibiotics--enrofloxacin, enoxacin, danofloxacin, and nalidixic acid--in groundwater and urine samples were used as analytes. The extraction recovery was found to be between 64.9 and 98.9%. The results showed high correlation coefficients (R2 > 0.992) for all of the analytes within the calibration range. The LOQ was between 0.091 and 0.315 ng/mL.

  4. Renaissance of antibiotics against difficult infections: Focus on oritavancin and new ketolides and quinolones.

    Science.gov (United States)

    Van Bambeke, Françoise

    2014-11-01

    Lipoglycopeptide, ketolide, and quinolone antibiotics are currently in clinical development, with specific advantages over available molecules within their respective classes. The lipoglycopeptide oritavancin is bactericidal against MRSA, vancomycin-resistant enterococci, and multiresistant Streptococcus pneumoniae, and proved effective and safe for the treatment of acute bacterial skin and skin structure infection (ABSSSI) upon administration of a single 1200 mg dose (two completed phase III trials). The ketolide solithromycin (two phase III studies recruiting for community-acquired pneumonia) shows a profile of activity similar to that of telithromycin, but in vitro data suggest a lower risk of hepatotoxicity, visual disturbance, and aggravation of myasthenia gravis due to reduced affinity for nicotinic receptors. Among quinolones, finafloxacin and delafloxacin share the unique property of an improved activity in acidic environments (found in many infection sites). Finafloxacin (phase II completed; activity profile similar to that of ciprofloxacin) is evaluated for complicated urinary tract and Helicobacter pylori infections. The other quinolones (directed towards Gram-positive pathogens) show improved activity on MRSA and multiresistant S. pneumoniae compared to current molecules. They are in clinical evaluation for ABSSSI (avarofloxacin (phase II completed), nemonoxacin and delafloxacin (ongoing phase III)), respiratory tract infections (zabofloxacin and nemonoxacin (ongoing phase III)), or gonorrhea (delafloxacin).

  5. Comparative sensitizing potencies of fragrances, preservatives, and hair dyes

    DEFF Research Database (Denmark)

    Lidén, Carola; Yazar, Kerem; Johansen, Jeanne Duus

    2016-01-01

    the sensitizing potencies of fragrance substances, preservatives, and hair dye substances, which are skin sensitizers that frequently come into contact with the skin of consumers and workers, LLNA results and EC3 values for 72 fragrance substances, 25 preservatives and 107 hair dye substances were obtained from...... two published compilations of LLNA data and opinions by the Scientific Committee on Consumer Safety and its predecessors. The median EC3 values of fragrances (n = 61), preservatives (n = 19) and hair dyes (n = 59) were 5.9%, 0.9%, and 1.3%, respectively. The majority of sensitizing preservatives...... and hair dyes are thus strong or extreme sensitizers (EC3 value of ≤2%), and fragrances are mostly moderate sensitizers. Although fragrances are typically moderate sensitizers, they are among the most frequent causes of contact allergy. This indicates that factors other than potency need to be addressed...

  6. Can biochemistry drive drug discovery beyond simple potency measurements?

    Science.gov (United States)

    Chène, Patrick

    2012-04-01

    Among the fields of expertise required to develop drugs successfully, biochemistry holds a key position in drug discovery at the interface between chemistry, structural biology and cell biology. However, taking the example of protein kinases, it appears that biochemical assays are mostly used in the pharmaceutical industry to measure compound potency and/or selectivity. This limited use of biochemistry is surprising, given that detailed biochemical analyses are commonly used in academia to unravel molecular recognition processes. In this article, I show that biochemistry can provide invaluable information on the dynamics and energetics of compound-target interactions that cannot be obtained on the basis of potency measurements and structural data. Therefore, an extensive use of biochemistry in drug discovery could facilitate the identification and/or development of new drugs.

  7. Incorporating potency into EU classification for carcinogenicity and reproductive toxicity.

    Science.gov (United States)

    Hennes, C; Batke, M; Bomann, W; Duhayon, S; Kosemund, K; Politano, V; Stinchcombe, S; Doe, J

    2014-11-01

    Although risk assessment, assessing the potential harm of each particular exposure of a substance, is desirable, it is not feasible in many situations. Risk assessment uses a process of hazard identification, hazard characterisation, and exposure assessment as its components. In the absence of risk assessment, the purpose of classification is to give broad guidance (through the label) on the suitability of a chemical in a range of use situations. Hazard classification in the EU is a process involving identification of the hazards of a substance, followed by comparison of those hazards (including degree of hazard) with defined criteria. Classification should therefore give guidance on degree of hazard as well as hazard identification. Potency is the most important indicator of degree of hazard and should therefore be included in classification. This is done for acute lethality and general toxicity by classifying on dose required to cause the effect. The classification in the EU for carcinogenicity and reproductive toxicity does not discriminate across the wide range of potencies seen (6 orders of magnitude) for carcinogenicity and for developmental toxicity and fertility. Therefore potency should be included in the classification process. The methodology in the EU guidelines for classification for deriving specific concentration limits is a rigorous process for assigning substances which cause tumours or developmental toxicity and infertility in experimental animals to high, medium or low degree of hazard categories by incorporating potency. Methods are suggested on how the degree of hazard so derived could be used in the EU classification process to improve hazard communication and in downstream risk management.

  8. Microwave-assisted one-pot synthesis of polycyclic 4-quinolone derivatives

    OpenAIRE

    2015-01-01

    A microwave-assisted solvent-free one-pot method to afford 1,2,3,4-tetrahydroacridines-9-one derivatives was developed, with shorter reaction time and from easily available starting materials compared to the known methods. Fil: Muscia, Gisela Celeste. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina; Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina; Fil: Carnev...

  9. The synthesis and activity in vitro of a series of 8-difluoromethoxy quinolones: Analogues of gemifloxacin

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    7-[4-(Aminomethyl)-3-(methoxyimino)pyrrolidin- 1-yl]-1-cyclopropyl-6-fluoro-8-difluoromethoxy- 1 ,4-dihydro-4-oxoquino-line-3-carboxylic acid and its analogues have been prepared and evaluated for antibacterial activityin vitro.

  10. Synthesis, Antimicrobial and Antitubercular Activities of Some Novel Carboxamide Derivatives of 2-Quinolones

    Directory of Open Access Journals (Sweden)

    Abhishek Kumar

    2014-12-01

    Full Text Available A series of novel substituted N-(3-acetyl-2-oxoquinolin-1(2H-ylbenzamide (AJQC1-AJQC12 have been synthesized upon refluxing 3-acetyl-1-amino-quinolin-2-one and substituted benzoic acid in the presence of dry redistilled pyridine and silicon tetra chloride as coupling agent. 3-acetyl-1-amino-quinolin-2-one (AJQ1-AJQ12 were synthesized from substituted 3-acetyl coumarin upon refluxing with hydrazine hydrate and ethanol. The structures of the final carboxamide derivatives were confirmed by IR, 1H NMR and mass spectra. The synthesized compounds were screened for their antimicrobial activity by tube dilution method and anti tubercular activity by microplate Alamar blue assay. Most of the compounds have exhibited promising antibacterial, anti fungal and anti tubercular activities.

  11. Synthesis and spectroscopic studies of iron (III) complex with a quinolone family member (pipemidic acid)

    Science.gov (United States)

    Skrzypek, D.; Szymanska, B.; Kovala-Demertzi, Dimitra; Wiecek, Joanna; Talik, E.; Demertzis, Mavroudis A.

    2006-12-01

    The interaction of iron (III) with pipemidic acid, Hpipem, afforded the complex [Fe (pipem) (HO)2 (H2O)]2. The new complex has been characterised by elemental analyses, infra-red, EPR and XPS spectroscopies. The monoanion, pipem, exhibits O, O ligation through the carbonyl and carboxylato oxygen atoms. Six coordinate dimer distorted octahedral configuration has been proposed for [Fe (pipem) (HO)2 (H2O)]2.

  12. Synthesis, spectral characterization and antimicrobial activity of substituted thiazolyl derivatives of 2-quinolones.

    Science.gov (United States)

    Katagi, M S; Bolakatti, G S; Badiger, A M; Satyanarayana, D; Mamledesai, S N; Sujatha, M L

    2013-02-01

    A series of new 3-(2-substituted amino/substituted hydrazino-1,3-thiazol-4-yl)-4-hydroxy-1-methyl/phenylquinolin-2 (1H)-one hydroiodide 3a-3f and 4a-4f derivatives were prepared by heating 3-Acetyl-4-hydroxy-1-methyl/phenyl quinolin-2 (1H)-one 2a-2b with substituted thiourea and substituted thiosemicarbazide in presence of iodine in n-butanol. The title compounds were characterized on the basis of IR, 1H NMR, 13C NMR and Mass spectral (MS) studies. Further title compounds were evaluated for antibacterial and antifungal by Agar diffusion assay method where as antitubercular activity by Micro-plate Alamar Blue Assay (MABA). Among 12 synthesized novel compounds 3a, 3b, 4d exhibited promising antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. 3a, 3b, 3e, 4d, 4e showed good antifungal activity against Candida albicans and Aspergillus niger. 3a, 3d, 4d showed good antitubercular activity against Mycobacterium tuberculosis H37Rv strain.

  13. Design and synthesis of novel quinolones directed to the Plasmodium falciparum bc1 protein complex

    OpenAIRE

    Horta, Pedro Filipe Castela

    2016-01-01

    Tese de Doutoramento, Química, Especialização em Química Orgânica, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2016 Apesar dos intensos esforços para controlo da malária, esta doença parasítica milenar permanece como uma das doenças infeciosas conducentes a maiores taxas de mortalidade no mundo. É transmitida pela picada de um mosquito infectado do género Anopheles (apenas a fémea transmite a doença) e causada por um parasita do género Plasmodium. P. falciparum é a mais pr...

  14. Characteristics of Quinolone Resistance in Salmonella spp. Isolates from the Food Chain in Brazil.

    Science.gov (United States)

    Pribul, Bruno R; Festivo, Marcia L; Rodrigues, Marcelle S; Costa, Renata G; Rodrigues, Elizabeth C Dos P; de Souza, Miliane M S; Rodrigues, Dalia Dos P

    2017-01-01

    Salmonella spp. is an important zoonotic pathogen related to foodborne diseases. Despite that quinolones/fluoroquinolones are considered a relevant therapeutic strategy against resistant isolates, the increase in antimicrobial resistance is an additional difficulty in controlling bacterial infections caused by Salmonella spp. Thus, the acquisition of resistance to quinolones in Salmonella spp. is worrisome to the scientific community along with the possibility of transmission of resistance through plasmids. This study investigated the prevalence of plasmid-mediated quinolone resistance (PMQR) in Salmonella spp. and its association with fluoroquinolone susceptibility in Brazil. We evaluated 129 isolates, 39 originated from food of animal sources, and 14 from environmental samples and including 9 from animals and 67 from humans, which were referred to the National Reference Laboratory of Enteric Diseases (NRLEB/IOC/RJ) between 2009 and 2013. These samples showed a profile of resistance for the tested quinolones/fluoroquinolones. A total of 33 serotypes were identified; S. Typhimurium (63) was the most prevalent followed by S. Enteritidis (25). The disk diffusion test showed 48.8% resistance to enrofloxacin, 42.6% to ciprofloxacin, 39.53% to ofloxacin, and 30.2% to levofloxacin. According to the broth microdilution test, the resistance percentages were: 96.1% to nalidixic acid, 64.3% to enrofloxacin, 56.6% to ciprofloxacin, 34.1% to ofloxacin, and 30.2% to levofloxacin. Qnr genes were found in 15 isolates (8 qnrS, 6 qnrB, and 1 qnrD), and the aac(6')-Ib gene in 23. The integron gene was detected in 67 isolates with the variable region between ±600 and 1000 bp. The increased detection of PMQR in Salmonella spp. is a serious problem in Public Health and must constantly be monitored. Pulsed-field gel electrophoresis was performed to evaluated clonal profile among the most prevalent serovars resistant to different classes of quinolones. A total of 33 pulsotypes of S

  15. Detection of quinolones in commercial eggs obtained from farms in the Espaíllat Province in the Dominican Republic.

    Science.gov (United States)

    Moscoso, S; de los Santos, F Solís; Andino, A G; Diaz-Sanchez, Sandra; Hanning, I

    2015-01-01

    Previously, we reported the use of quinolones in broiler chickens resulted in residues in retail poultry meat obtained from nine districts in the Santiago Province of the Dominican Republic. Residues in poultry products are a concern due to consumer allergies and the potential to develop antibiotic-resistant bacteria. Given the use of quinolones in poultry production and our previous findings in poultry meat, the objective of this study was to evaluate the presence of quinolone residues in eggs. Samples were collected from 48 different farms located in three of the four municipalities (Moca, Cayetano Germosén, and Jamao) of the Espaíllat Province. Each farm was sampled three times between July and September for a total of 144 samples. Samples were evaluated qualitatively and quantitatively for quinolone residues using the Equinox test. Operation systems (cage or floor), seasonality, and location were considered along with egg-producer sizes that were defined as small scale, 60,000 eggs per day. From small-, medium-, and large-scale producers, 69, 50, and 40% of samples were positive for quinolone residues, respectively. A greater number of samples were positive (61%) in floor-laying hen producers compared with those using cages (40%). In the Jamao municipality, 67% of the samples were positive compared with Moca and Cayetano Germosén, where 56 and 25% of samples were positive, respectively. Sampling time had an effect on percent positives: samples collected in July, August, and September were 71, 19, and 63% positive, respectively. Overall, 51% of the samples obtained from eggs produced in the province of Espaíllat were positive for quinolone residues at levels higher than the maximum limits for edible tissue established by the regulatory agencies, including the European Union and U.S. Department of Agriculture. The results obtained from this research confirmed the presence of quinolone residue in eggs, which may present a health risk to some consumers.

  16. Epoxy resin monomers with reduced skin sensitizing potency.

    Science.gov (United States)

    O'Boyle, Niamh M; Niklasson, Ida B; Tehrani-Bagha, Ali R; Delaine, Tamara; Holmberg, Krister; Luthman, Kristina; Karlberg, Ann-Therese

    2014-06-16

    Epoxy resin monomers (ERMs), especially diglycidyl ethers of bisphenol A and F (DGEBA and DGEBF), are extensively used as building blocks for thermosetting polymers. However, they are known to commonly cause skin allergy. This research describes a number of alternative ERMs, designed with the aim of reducing the skin sensitizing potency while maintaining the ability to form thermosetting polymers. The compounds were designed, synthesized, and assessed for sensitizing potency using the in vivo murine local lymph node assay (LLNA). All six epoxy resin monomers had decreased sensitizing potencies compared to those of DGEBA and DGEBF. With respect to the LLNA EC3 value, the best of the alternative monomers had a value approximately 2.5 times higher than those of DGEBA and DGEBF. The diepoxides were reacted with triethylenetetramine, and the polymers formed were tested for technical applicability using thermogravimetric analysis and differential scanning calorimetry. Four out of the six alternative ERMs gave polymers with a thermal stability comparable to that obtained with DGEBA and DGEBF. The use of improved epoxy resin monomers with less skin sensitizing effects is a direct way to tackle the problem of contact allergy to epoxy resin systems, particularly in occupational settings, resulting in a reduction in the incidence of allergic contact dermatitis.

  17. Comparative anticonvulsant potency and pharmacokinetics of (+)-and (-)-enantiomers of stiripentol.

    Science.gov (United States)

    Shen, D D; Levy, R H; Savitch, J L; Boddy, A V; Tombret, F; Lepage, F

    1992-06-01

    The anticonvulsant potency and pharmacokinetics of the enantiomers of stiripentol were compared using the intravenous pentylenetetrazol infusion seizure model in the rat. Enantioselectivity was observed with respect to both the anticonvulsant activity and elimination kinetics of this compound. (+)-Stiripentol was 2.4 times more potent than its antipode against pentylenetetrazol-induced clonic seizure (brain EC50 of 15.2 micrograms/ml versus 36.1 micrograms/ml). The (+)-enantiomer was eliminated more rapidly than the (-)-enantiomer, as reflected in a higher plasma clearance (1.64 l/h/kg versus 0.557 l/h/kg) and a shorter half-life (2.83 h versus 6.50 h). Parallel studies with the racemate of stiripentol indicated that the anticonvulsant potency of the racemate was between the potency of the two enantiomers, suggesting that the combined activity reflects the additive action of (+)- and (-)-stiripentol. However, a marked metabolic interaction between enantiomers was evident after racemate administration. These results point to the need for information on the differential pharmacokinetics of stiripentol enantiomers following racemic drug administration.

  18. Dynamics of Antagonistic Potency of Rhodobacter capsulatus PG Lipopolysaccharide against Endotoxin-Induced Effects.

    Science.gov (United States)

    Kabanov, D S; Serov, D A; Zubova, S V; Grachev, S V; Prokhorenko, I R

    2016-03-01

    The dynamics of antagonistic potency of lipopolysaccharide (LPS) isolated from Rhodobacter capsulatus PG on the synthesis of proinflammatory (TNF-α, IL-1β, IL-8, IL-6, IFN-γ) and antiinflammatory (IL-10, IL-1Ra) cytokines induced by highly stimulatory endotoxins from Escherichia coli or Salmonella enterica have been studied. Using human whole blood, we have shown that R. capsulatus PG LPS inhibited most pronouncedly the endotoxin-induced synthesis of TNF-α, IL-1β, IL-8, and IL-6 during the first 6 h after endotoxin challenge. Similarly, the endotoxin-induced release of IFN-γ was abolished by R. capsulatus PG LPS as well (24 h). In contrast to the above-mentioned cytokines, the relatively weak antagonistic activity of R. capsulatus PG LPS against endotoxin-triggered production of IL-6 and IL-8 was revealed. Since R. capsulatus PG LPS displays more potent antagonistic activity against deleterious effects of S. enterica LPS than those of E. coli LPS in the cases of such cytokines as IL-1β (6 and 24 h), IL-6 and IL-8 (4 h), we conclude that the effectiveness of protective action of antagonist is mostly determined by the primary lipid A structure of the employed agonist.

  19. Looking for the new preparations for antibacterial therapy III. New antimicrobial agents from the quinolones group in clinical trials.

    Science.gov (United States)

    Karpiuk, Izabela; Tyski, Stefan

    2013-01-01

    There is an essential need for searching for the new compounds effective in the treatment of infections caused by multidrug-resistant bacteria. This paper is the third part of a series associated with the exploration of new antibacterial agents and it discusses the compounds belonging to the group of quinolones and substances possessing a hybrid structure composed of the quinolone molecule and other compounds. Eleven new substances at the stage of clinical trials are presented. Three of them belong to the group of non-fluorinated quinolone (nemonoxacin, ozenoxacin and KRP-AM 1977X), while six are the quinolones containing fluorine atom at 6 position of the carbon atom in the quinoline ring (zabofloxacin, finafloxacin, delafloxacin, JNJ-Q2, WCK771 and KPI-10). The remaining two compounds possess a hybrid construction composed of the quinolone structure and other molecules (cadazolid and CBR-2092). There is a chance in the near future, that the presented compounds can extend the range of existing antibacterial drugs and provide an alternative to currently available medicinal products.

  20. High-level quinolone resistance is associated with the overexpression of smeVWX in Stenotrophomonas maltophilia clinical isolates.

    Science.gov (United States)

    García-León, G; Ruiz de Alegría Puig, C; García de la Fuente, C; Martínez-Martínez, L; Martínez, J L; Sánchez, M B

    2015-05-01

    Stenotrophomonas maltophilia is the only known bacterium in which quinolone-resistant isolates do not present mutations in the genes encoding bacterial topoisomerases. The expression of the intrinsic quinolone resistance elements smeDEF, smeVWX and Smqnr was analysed in 31 clinical S. maltophilia isolates presenting a minimum inhibitory concentration (MIC) range to ciprofloxacin between 0.5 and > 32 μg/mL; 11 (35.5%) overexpressed smeDEF, 2 (6.5%) presenting the highest quinolone MICs overexpressed smeVWX and 1 (3.2%) overexpressed Smqnr. Both strains overexpressing smeVWX presented changes at the Gly266 position of SmeRv, the repressor of smeVWX. Changes at the same position were previously observed in in vitro selected S. maltophilia quinolone-resistant mutants, indicating this amino acid is highly relevant for the activity of SmeRv in repressing smeVWX expression. For the first time SmeVWX overexpression is associated with quinolone resistance of S. maltophilia clinical isolates.

  1. Using SAR and QSAR analysis to model the activity and structure of the quinolone-DNA complex.

    Science.gov (United States)

    Llorente, B; Leclerc, F; Cedergren, R

    1996-01-01

    A set of 78 quinolone derivatives were used in a structure-activity study to identify structural features correlating with antibacterial activity. Distinct combinations of functional properties were identified for Gram-negative and Gram-positive bacteria. 3-D Quantitative structure-activity relationship (QSAR) studies identified specific hydrophobic, topologic and electronic properties of the molecules for both in vitro and in vivo activities. From these results, a three-dimensional model of a DNA-quinolone complex was built using molecular modeling techniques. It was based on the intercalation of quinolone into the double helix of DNA. We conclude that the intercalation model is consistent with most available data on the structure of the quinolone complex. This predicted structure is stabilized by the binding of magnesium ion with the sp2 oxygens present in quinolone, a phosphate and a purine base of the DNA. Substituents R1 and R7 are predicted to make hydrophobic interactions in the major and minor groove of DNA, respectively. R7 could also form hydrogen bonds with amino groups of guanines and the aspartic acid residue at position 87 in DNA gyrase subunit A.

  2. The molecular physiological and genetic mechanisms underlying the superb efficacy of quinolones%喹诺酮类药物作用的生理和遗传的分子机制

    Institute of Scientific and Technical Information of China (English)

    龙泉鑫; 何颖; 谢建平

    2012-01-01

    氟喹诺酮类药物是目前使用最广泛的广谱抗生素,占据了全球抗生素类药物市场约18%的份额.其杀菌快速,而且具备大量的衍生物库,为药物更新换代提供了良好的基础.但这些衍生物在杀菌的速度、代谢过程中对氧需求、对蛋白合成的依赖性等方面的差异很大.从药物作用后细菌分子遗传层面的应答特征揭示各类衍生物的深层次作用机制,可以为寻找更有效的新喹诺酮类药物提供坚实基础.SOS应答、毒素-抗毒素系统,细菌程序性死亡、染色体片段化以及活性氧簇等新机制可能不同程度参与了喹诺酮类药物的杀菌过程.本文重点介绍喹诺酮作用的“二步特征”.该特征的引入有助于理解不同喹诺酮类药物的杀菌特征,也有助于开发新的喹诺酮类药物.%The fluoroquinolones are the most widely used broad-spectrum antibiotics, accounting for 18% of global antibacterial market share. They can kill bacteria rapidly with variety of derivatives available. Different quinolones vary significantly in rate and spectrum of killing, oxygen requirement for metabolism and reliance upon protein synthesis. Further understanding the sophisticated mechanisms of action of this important antibiotic family based on the molecular genetic response of bacteria can facilitate the discovery of better quinolone derivatives. Factors such as SOS response, bacterial toxin-antitoxin system, programmed death, chromosome fragmentation and reactive oxygen have been implicated in the action to some extent. "Two steps characteristic" of quinolones killing is also emphasized, which might inspire future better quinolones modification.

  3. Potency of Microalgae as Biodiesel Source in Indonesia

    Directory of Open Access Journals (Sweden)

    H Hadiyanto

    2012-02-01

    Full Text Available Within 20 years, Indonesia should find another energy alternative to substitute current fossil oil. Current use of renewable energy is only 5% and need to be improved up to 17% of our energy mix program. Even though, most of the area in Indonesia is covered by sea, however the utilization of microalgae as biofuel production is still limited. The biodiesel from current sources (Jatropha, palm oil, and sorghum is still not able to cover all the needs if the fossil oil cannot be explored anymore. In this paper, the potency of microalgae in Indonesia was analysed as the new potential of energy (biodiesel sources.

  4. Potency of Microalgae as Biodiesel Source in Indonesia

    Directory of Open Access Journals (Sweden)

    H Hadiyanto

    2012-04-01

    Full Text Available Within 20 years, Indonesia should find another energy alternative to substitutecurrent fossil oil. Current use of renewable energy is only 5% and need to be improved up to 17%of our energy mix program. Even though, most of the area in Indonesia is covered by sea, howeverthe utilization of microalgae as biofuel production is still limited. The biodiesel from currentsources (Jatropha, palm oil, and sorghum is still not able to cover all the needs if the fossil oilcannot be explored anymore. In this paper, the potency of microalgae in Indonesia was analysed asthe new potential of energy (biodiesel sources.

  5. The Potency of Krokot (Portulaca oleracea) as Functional Food Ingredients

    OpenAIRE

    Irawan, Daisy; Hariyadi, Purwiyatno; Wijaya, Hanny

    2014-01-01

    Indonesia has many auxiliary plants that may have nutritional and or environmental benefits, so that it may increase the yield of the main crops. Krokot (Portulaca oleracea), one of the auxiliary plants, was traditionally consumed in many parts of the world for its delicacy and medicinal benefits. Our research indicated that krokot has high potency to improve the health status of the community. It has 5.4 mg/100 g of b-carotene, 22.2 mg/100 g of vitamin C, and significant amount of folic acid...

  6. Cannabis-induced psychosis associated with high potency "wax dabs".

    Science.gov (United States)

    Pierre, Joseph M; Gandal, Michael; Son, Maya

    2016-04-01

    With mounting evidence that the risk of cannabis-induced psychosis may be related to both dose and potency of tetrahydrocannbinol (THC), increasing reports of psychosis associated with cannabinoids containing greater amounts of THC are anticipated. We report two cases of emergent psychosis after using a concentrated THC extract known as cannabis "wax," "oil," or "dabs" raising serious concerns about its psychotic liability. Although "dabbing" with cannabis wax is becoming increasingly popular in the US for both recreational and "medicinal" intentions, our cases raise serious concerns about its psychotic liability and highlight the importance of understanding this risk by physicians recommending cannabinoids for purported medicinal purposes. Published by Elsevier B.V.

  7. Why are ototopical aminoglycosides still first-line therapy for chronic suppurative otitis media? A systematic review and discussion of aminoglycosides versus quinolones.

    Science.gov (United States)

    Harris, A S; Elhassan, H A; Flook, E P

    2016-01-01

    This systematic review aimed to establish that quinolones are as effective as aminoglycosides when used to treat chronic suppurative otitis media. The review included good quality, randomised, controlled trials on human subjects, published in English, that compared topical aminoglycosides with topical quinolones for the treatment of chronic suppurative otitis media. Nine trials met the criteria. Two studies showed a higher clinical cure rate in the quinolone group (93 per cent vs 71 per cent, p = 0.04, and 76 per cent vs 52 per cent, p = 0.009). Four studies showed no statistically significant difference in clinical outcome. A significant difference in microbiological clearance in favour of quinolones was shown in two studies (88 per cent vs 30 per cent, p otitis media and when used as prophylaxis post-myringotomy. Topical quinolones should be considered a first-line treatment for these patients.

  8. USE OF QUINOLONES IN BULL SEMEN EXTENDERS TO REDUCE SPERM DEOXYRIBONUCLEIC ACID DAMAGE

    Directory of Open Access Journals (Sweden)

    Clara Gonzalez-Marin

    2012-01-01

    Full Text Available Cryopreserved sperm samples from Holstein bulls (n = 20 were examined for bacterial presence and Sperm DNA Fragmentation (SDF dynamics. SDF was assessed after thawing (T0 and at 4, 24 and 48 h of incubation (37°C and the rate of SDF (r-SDF, as an estimator of the DNA degradation over time, was calculated. Two groups of bulls were identified based on the presence or absence of bacteria: One group (n = 10 had a readily detectable bacterial presence, while the other group (n = 10 had an undetectable bacterial presence. Differences in the SDF at T0 were not observed between these two groups. However, statistically different results were found after 24 h of incubation at 37°C (Kaplan-Meier estimator; Log-Rank Matel-Cox, p-1 of ciprofloxacin at T0. Differences in the r-SDF (p>0.05 were not detected between the control and the quinolone treated sample for those samples without bacteria. However, differences (p<0.000 in SDF were observed for quinolone treated samples that previously presented bacteria. Incubation of sealed straws showed that bacterial contamination occurred prior to cryopreservation. These results call attention to three points: (1 sperm samples were in contact with bacteria before cryopreservation; (2 the r-SDF can be directly correlated with bacterial presence but this effect remains cryptic after thawing and (3 the r-SDF can be reduced by treating the semen samples with an adequate antibiotic such as quinolones, a finding not previously reported in the scientific literature, but important in terms of reproduction.

  9. Characterization of quinolone resistance mechanisms in Enterobacteriaceae recovered from diseased companion animals in Europe.

    Science.gov (United States)

    Guillard, T; de Jong, A; Limelette, A; Lebreil, A L; Madoux, J; de Champs, C

    2016-10-15

    ComPath is a European monitoring programme dedicated to the collection of bacterial pathogens from diseased dogs and cats to determine their antibiotic susceptibility. The objective was to characterize genetic determinants associated with quinolone resistance among 69 enrofloxacin non-wild type strains selected among 604 non-duplicate Enterobacteriaceae isolates collected in 10EU countries from 2008 to 2010: quinolone resistance determining region (QRDR) and plasmid-mediated quinolone resistance (PMQR). Among them, 17% (12/69) carried at least one PMQR (9/12 qnrB, qnrS or qnrD and 4/12 aac(6')-Ib-cr) and 83% (57/69) no PMQR. All the Klebsiella pneumoniae isolates chromosomally carried oqxAB . No qepA genes were detected. Eight strains did not carry any mutations in QRDR (4 PMQR-positive and 4 PMQR-negative strains). From the 12 PMQR-positive strains, 4 showed enrofloxacin MICs≤2μg/mL, and 8 MICs≥8μg/mL (resistant). These latter strains carried 1-5 mutations in QRDR, including a ParE I529L mutation. qnrD was found in 2 Proteus mirabilis and the plasmids were similar to pDIJ09-518a previously described. For the 57 non-PMQR strains, 29 strains showed MICs≤2μg/mL (4 with no QRDR mutations, 21 with 1 mutation in GyrA, 4 with 2 mutations in GyrA) and 28 showed enrofloxacin MICs≥8μg/mL carrying at least 2 mutations in QRDR, including a ParE I529L mutation for 2 Escherichia coli strains with a total of 5 QRDR mutations. No GyrB mutations were found. qnr was the major PMQR and qnrD was only detected in Proteus spp. Twelve strains carried at least 4 mutations.

  10. Genetic analysis of a pediatric clinical isolate of Moraxella catarrhalis with resistance to macrolides and quinolones.

    Science.gov (United States)

    Iwata, Satoshi; Sato, Yoshitake; Toyonaga, Yoshikiyo; Hanaki, Hideaki; Sunakawa, Keisuke

    2015-04-01

    During the surveillance conducted in 2012 by the Drug-resistant Pathogen Surveillance Group in Pediatric Infectious Disease, we isolated a strain of Moraxella catarrhalis that demonstrated resistance to both macrolides and quinolones from a male pediatric patient aged 1.5 years who had developed acute bronchitis. Then we evaluated the susceptibility of this strain to different types of antibacterial agents and conducted a genetic analysis. The results of the susceptibility evaluation showed that the MIC values of azithromycin, clarithromycin, and rokitamycin were >64 μg/mL, >64 μg/mL, and 4 μg/mL, respectively; clearly demonstrating resistance to macrolides. The MIC values of the quinolones levofloxacin, tosufloxacin, and garenoxacin were 4 μg/mL, 2 μg/mL, and 1 μg/mL, respectively; indicating decreased susceptibility. The genetic analysis of this strain revealed one mutation in 23s rRNA with a replacement of adenine by thymine at nucleotide position 2330 (A2330T) and another mutation in gyrB at nucleotide position 1481 by replacement of adenine with guanine (A1481G) that caused a substitution of the 494 th asparagine acid by glycine, as being associated with the observed resistance to macrolides and quinolones, respectively. Similar to drug-resistant bacteria Streptococcus pneumoniae and Haemophilus influenzae, the prevalence of which has recently increased, the treatment of drug-resistant M. catarrhalis infections is considered difficult due to the development of resistance to different types of antibacterial agents. It is vital to maintain an unwavering focus on the trend toward an increasing number of drug-resistant M. catarrhalis strains and ensure the proper use of each antibacterial agent.

  11. Molecular epidemiological survey on quinolone resistance genotype and phenotype of Escherichia coli in septicemic broilers in Hebei, China.

    Science.gov (United States)

    Xie, Rong; Huo, Shuying; Li, Yurong; Chen, Ligong; Zhang, Feiyan; Wu, Xianjun

    2014-02-01

    In this study, the quinolone-resistant determining region (QRDR) of gyrA of Escherichia coli and plasmid-mediated quinolone resistance (PMQR) genes, qnr(qnrA, qnrB, and qnrS), and aac(6 ')-Ib-cr were detected, sequenced, and analyzed. In addition, antimicrobial susceptibility tests (using the Kirby-Bauer disc diffusion method) were performed for all 111 E. coli isolates from septicemic broilers in Hebei, China. The results show that the resistance rates were as follows: ofloxacin 99.10%, ciprofloxacin 93.69%, levofloxacin 91.89%, norfloxacin 90.09%, and gatifloxacin 76.58%. Of the PMQR genes examined, aac(6 ')-Ib-cr (36.04%) was the most frequently identified gene in all isolates, followed by qnrS (8.11%), qnrB (0.90%), and qnrA (0%). Of the QRDR examined in the 40 phenotypic quinolone-resistant isolates, compared with the gyrA(+) gene of E. coli K-12, 4 amino acid exchanges were found, namely Ser-83→Asp, Asp-87→Asn, Asp-87→Tyr, and Asp-87→Ala, and all 40 isolates had 1 or 2 exchanges in QRDR. It was concluded that quinolone-resistance in E. coli remains a serious problem in Hebei, China. Therefore, there is considerable local surveillance of quinolone resistance. Plasmid-mediated quinolone resistance of the qnr type remains rare in Hebei, China, and mutation in QRDR may be the main problem.

  12. Quinolone Resistance among Salmonella enterica from Cattle, Broilers and Swine in Denmark

    DEFF Research Database (Denmark)

    Wiuff, C.; Baggesen, Dorte Lau; Madsen, M.

    2000-01-01

    This study was conducted to determine the susceptibility to nalidixic acid and fluoroquinolones of Salmonella Dublin, S. Enteritidis, and S. Typhimurium isolates from cattle, broilers, and pigs over time in Denmark and to characterise the gyrA, gyrB, and parC genes in quinolone-resistant isolates......, and one from 1999 were resistant to nalidixic acid. All the nalidixic acid-resistant isolates had reduced susceptibility to fluoroquinolones. Sequence analysis of the gyrA gene in 37 nalidixic-resistant isolates identified two different base substitutions at codon serine-83 and two at aspartate-87...

  13. Comparison of Antimicrobial Properties of Nano Quinolone with its Microscale Effects

    Science.gov (United States)

    Behbahani, G. Rezaie; Sadr, M. Hossaini; Nabipour, H.; Behbahani, H. Rezaei; Vahedpour, M.; Barzegar, L.

    2013-06-01

    Nano nalidixic acid was prepared by ultrasonic method in carbon tetrachloride. Nano nalidixic acid (quinolone antibiotic) was characterized by X-ray diffraction (XRD), infrared spectroscopy (IR) and scanning electron microscope (SEM). The antibacterial activities of nano nalidixic acid were tested against microorganisms and compared with the microscale drug. The results show that nano nalidixic acid has good inhibitory properties against two Gram-positive species, Staphylococcus aureus and Bacillus subtilis. Nano nalidixic acid also showed good antifungal activity against Candida albicans. Nano nalidixic acid can be injected into the human body as a decontaminating agent to prevent the growth of harmful microorganisms more effectively than the micro-sized drug.

  14. QSAR study and VolSurf characterization of anti-HIV quinolone library

    Science.gov (United States)

    Filipponi, Enrica; Cruciani, Gabriele; Tabarrini, Oriana; Cecchetti, Violetta; Fravolini, Arnaldo

    2001-03-01

    Antiviral quinolones are promising compounds in the search for new therapeutically effective agents for the treatment of AIDS. To rationalize the SAR for this new interesting class of anti-HIV derivatives, we performed a 3D-QSAR study on a library of 101 6-fluoro and 6-desfluoroquinolones, taken either from the literature or synthesized by us. The chemometric procedure involved a fully semiempirical minimization of the molecular structures by the AMSOL program, which takes into account the solvatation effect, and their 3D characterization by the VolSurf/GRID program. The QSAR analysis, based on PCA and PLS methods, shows the key structural features responsible for the antiviral activity.

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

    Science.gov (United States)

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

    2007-02-01

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

  16. Affinity of 3-acyl substituted 4-quinolones at the benzodiazepine site of GABAA receptors

    DEFF Research Database (Denmark)

    Lager, Erik; Nilsson, Jakob; Nielsen, Elsebet Østergaard

    2008-01-01

    The finding that alkyl 1,4-dihydro-4-oxoquinoline-3-carboxylate and N-alkyl-1,4-dihydro-4-oxoquinoline-3-carboxamide derivatives may be high-affinity ligands at the benzodiazepine binding site of the GABA(A) receptor, prompted a study of 3-acyl-1,4-dihydro-4-oxoquinoline (3-acyl-4-quinolones......). In general, the affinity of the 3-acyl derivatives was found to be comparable with the 3-carboxylate and the 3-carboxamide derivatives, and certain substituents (e.g., benzyl) in position 6 were again shown to be important. As it is believed that the benzodiazepine binding site is situated between an alpha...

  17. Quinolone and macrolide resistance in Campylobacter jejuni and C-coli: Resistance mechanisms and trends in human isolates

    DEFF Research Database (Denmark)

    Engberg, J.; Aarestrup, Frank Møller; Taylor, D. E.

    2001-01-01

    The incidence of human Campylobacter jejuni and C. coli infections has increased markedly in many parts of the world in the last decade as has the number of quinolone-resistant and, to a lesser extent, macrolide-resistant Campylobacter strains causing infections. We review macrolide and quinolone...... resistance in Campylobacter and track resistance trends in human clinical isolates in relation to use of these agents in food animals. Susceptibility data suggest that erythromycin and other macrolides should remain the drugs of choice in most regions, with systematic surveillance and central measures...... maintained, but fluoroquinolones may now be of limited use in the empiric treatment of Campylobacter infections in many regions....

  18. Functions of a GyrBA fusion protein and its interaction with QnrB and quinolones.

    Science.gov (United States)

    Chen, Chunhui; Villet, Regis; Jacoby, George A; Hooper, David C

    2015-11-01

    In order to study the interactions between Escherichia coli DNA gyrase and the gyrase interacting protein QnrB in vivo, we constructed a gyrB-gyrA fusion and validated its ability to correct the temperature-sensitive growth of gyrA and gyrB mutants. Like wild-type gyrA, the gyrB-gyrA fusion complemented a quinolone-resistant gyrA mutant to increase susceptibility. It functioned as an active type II topoisomerase, catalyzed negative supercoiling of DNA, was inhibited by quinolone, and was protected by QnrB.

  19. Geohydrology, geochemistry, geothermal potency of Rianiate Toba Lake North Sumatera

    Science.gov (United States)

    Nainggolan, Juliper; Sitepu, Cristin; Pardede, Sanggam; Diantoro, Markus

    2017-09-01

    This research was performed to determine the potency of Rianiate’s geothermal an alternative of energy source and determine the types of geothermal that was begun with the position’s measurement by using GPS (Global Position System), and then the direct observation of chemical and physical properties such as pH, surface’s temperature, color etc. The following steps were taking sample in four different springs indicated by spring 1, spring 2, spring 3, and spring 4. The chemical nature was measured by titrimetry method by using AAS, XRD, and gas Chromathology. The calculating of temperature of subsurface has done by using geothermometer and sequentially followed by geothermal potency’s calculation. The position of four springs are located about N: 02° 31,852’ and E: 098° 44. 021’ where were average height from sea’s level is 958 m. The highest surface’s temperature is 80 °C and the temperature under soil is about 130.5 °C described the average of geothermal. The calculation of content of chloride, sulfate, bicarbonations revealed that the water can be categorized as chloride type. The trilateral diagram Na/1000 – K/100 - √Mg of hot water is in the regime of immature water. From the calculation of Indonesia’s Standardized Geotherm, it was obtained that the estimated reservoir potency of Rianiate geotherm is 2,68 MWe.

  20. PROBIOTIC POTENCY OF LACTOBACILLUS SPP. ISOLATED FROM SUMBAWA MARE MILK

    Directory of Open Access Journals (Sweden)

    I Nengah Sujaya

    2008-03-01

    Full Text Available This research was deigned to elucidate the potency of Lactobacillus spp. isolated from sumbawa mare milk to be developed as a probiotic. Sixteen lacobacilli were screened based on their resitancy to a model of gastric juice at pH 2, 3, and 4, then followed by their resistncy to small intestional fluid model containing deoxycholic. Three lactobacilli i.e. Lactobacillus sp. SKA13, Lactobacillus rhamnosus SKG34 and Lactobacillus rhamnosus SKG49 were found to be resistentent to gastric juice at pH 3 and 4. However, there were no lactobacilli resisted to pH 2. Lactobacillus rhamnosus SKG34 and Lactobacillus rhamnosus SKG49 were able to reach the colon even after being expossed to a model of intestinal fluid containing 0,4 mM deoxycholate and pancreatine. Therefore, these isolates have a potency to be developed as probiotic lactobacilli. Nevertherless, these lactobcailli could probably transform cholic acid into secondary bile acids, which were not expected to be found in the probiotic, and this capability is not appropriate for probiotic. This character is worthly to be studied since it has never been reported in lactobacilli.

  1. Synthesis of 5,6-Dihydro-OSW-1 and Its Antitumor Activities

    Institute of Scientific and Technical Information of China (English)

    DENG Le-Hua邓乐华; Wu Hao吴浩; YU Biao俞飚; JIANG Man-Rong蒋满荣; WU Jia-Rui吴家睿

    2004-01-01

    5,6-Dihydro-OSW-1 (1) was synthesized following our previous procedure for the total synthesis of OSW-1.This compound demonstrated slightly stronger potency than that of OSW-1 against the growth of cancer cells.

  2. Quantitative determination of quinolones residues in milk by HPLC-FLD

    Directory of Open Access Journals (Sweden)

    Marilena Gili

    2012-10-01

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

  3. Structure based in silico analysis of quinolone resistance in clinical isolates of Salmonella Typhi from India.

    Science.gov (United States)

    Kumar, Manoj; Dahiya, Sushila; Sharma, Priyanka; Sharma, Sujata; Singh, Tej P; Kapil, Arti; Kaur, Punit

    2015-01-01

    Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC) of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase.

  4. Adsorption of quinolone, tetracycline, and penicillin antibiotics from aqueous solution using activated carbons: Review.

    Science.gov (United States)

    Ahmed, Muthanna J

    2017-03-01

    Antibiotics, an important type of pharmaceutical pollutant, have attracted many researchers to the study of their removal from aqueous solutions. Activated carbon (AC) has been widely used as highly effective adsorbent for antibiotics because of its large specific surface area, high porosity, and favorable pore size distribution. In this article, the adsorption performance of AC towards three major types of antibiotics such as tetracyclines, quinolones, and penicillins were reviewed. According to collected data, maximum adsorption capacities of 1340.8, 638.6, and 570.4mg/g were reported for tetracyclines, quinolones, and penicillins, respectively. The values of 1/n for Freundlich isotherm were less than unity, suggesting that the adsorption was nonlinear and favorable. Adsorption kinetics followed closely the pseudo-second-order model and analysis using the Weber-Morris model revealed that the intra-particle diffusion was not the only rate controlling step. AC adsorption demonstrated superior performance for all selected drugs, thus being efficient technology for treatment of these pollutants.

  5. [Effect of pazufloxacin mesilate, a new quinolone antibacterial agent, for intravenous use on QT interval].

    Science.gov (United States)

    Fukuda, Hitoshi; Morita, Yukie; Shiotani, Norio; Mizuo, Midori; Komae, Norihisa

    2004-08-01

    The potential for QT interval prolongation of pazufloxacin mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, was investigated by in vitro and in vivo electrophysiology studies. Following results were obtained. In vitro electrophysiology study using guinea pig papillary muscles: PZFX mesilate (30-300 microM) had no effects on resting membrane potential (RMP), action potential amplitude (APA) and action potential duration (APD). Reference quinolones, sparfloxacin (3-30 microM) and moxifloxacin (10-100 microM), had no effects on RMP and APA, but significantly prolonged APD at more than 3 and 10 microM, respectively, while ciprofloxacin (10-100 microM) had no effect on each parameter. In vivo electrophysiology study using anesthetized dogs: PZFX mesilate had no effects on electrocardiograph parameter (PR interval, QRS interval, QT interval and QTc) after intravenous administration of 3-30 mg/kg. These results suggest that PZFX mesilate has low potential for QT interval prolongation.

  6. Bacterial plasmid-mediated quinolone resistance genes in aquatic environments in China

    Science.gov (United States)

    Yan, Lei; Liu, Dan; Wang, Xin-Hua; Wang, Yunkun; Zhang, Bo; Wang, Mingyu; Xu, Hai

    2017-01-01

    Emerging antimicrobial resistance is a major threat to human’s health in the 21st century. Understanding and combating this issue requires a full and unbiased assessment of the current status on the prevalence of antimicrobial resistance genes and their correlation with each other and bacterial groups. In aquatic environments that are known reservoirs for antimicrobial resistance genes, we were able to reach this goal on plasmid-mediated quinolone resistance (PMQR) genes that lead to resistance to quinolones and possibly also to the co-emergence of resistance to β-lactams. Novel findings were made that qepA and aac-(6′)-Ib genes that were previously regarded as similarly abundant with qnr genes are now dominant among PMQR genes in aquatic environments. Further statistical analysis suggested that the correlation between PMQR and β-lactam resistance genes in the environment is still weak, that the correlations between antimicrobial resistance genes could be weakened by sufficient wastewater treatment, and that the prevalence of PMQR has been implicated in environmental, pathogenic, predatory, anaerobic, and more importantly, human symbiotic bacteria. This work provides a comprehensive analysis of PMQR genes in aquatic environments in Jinan, China, and provides information with which combat with the antimicrobial resistance problem may be fought. PMID:28094345

  7. Analysis of quinolones by voltage-assisted liquid-phase microextraction combined with LC-MS.

    Science.gov (United States)

    Wang, Mi-Hung; Wang, Shu-Ping

    2012-03-01

    The method of liquid-phase microextraction assisted with voltage was developed and applied on determination of quinolones in water sample in this study. Both of the reproducibility and extraction time were improved with the aid of applying voltage. Four analytes in neutral state such as cinoxacin, oxolinic acid, nalidixic acid, and flumequine were extracted from a sample solution at pH 2.0, through a polypropylene hollow fiber which was immobilized with 2-octanone, and then into a 25 μL of the acceptor phase of 40 mM borate buffer at pH 10.0 by applying voltage of 100 V. Subsequently, the acceptor solution was directly subjected to analysis by LC-MS. The performance of the method for four quinolones was also evaluated. Linearity was obtained in the range of 1.0-25.0 ng/mL with R(2) > 0.996. Limits of detection were below 0.6 ng/mL, and recoveries of water sample were ranged from 90.8 to 109.6%.

  8. Lack of efflux mediated quinolone resistance in Salmonella enterica serovars Typhi and Paratyphi A

    Directory of Open Access Journals (Sweden)

    Sylvie eBaucheron

    2014-01-01

    Full Text Available Salmonella enterica serovars Typhi and Paratyphi A isolates from human patients in France displaying different levels of resistance to quinolones or fluoroquinolones were studied for resistance mechanisms to these antimicrobial agents. All resistant isolates carried either single or multiple target gene mutations (i.e. in gyrA, gyrB, or parC correlating with the resistance levels observed. Active efflux, through upregulation of multipartite efflux systems, has also been previously reported as contributing mechanism for other serovars. Therefore, we investigated also the occurrence of non-target gene mutations in regulatory regions affecting efflux pump expression. However, no mutation was detected in these regions in both Typhi and Paratyphi isolates of this study. Besides, no overexpression of the major efflux systems was observed for these isolates. Nevertheless, a large deletion of 2334 bp was identified in the acrS-acrE region of all S. Typhi strains but which did not affect the resistance phenotype. As being specific to S. Typhi, this deletion could be used for specific molecular detection purposes. In conclusion, the different levels of quinolone or FQ resistance in both S. Typhi and S. Paratyphi A seem to rely only on target modifications.

  9. Structure Based In Silico Analysis of Quinolone Resistance in Clinical Isolates of Salmonella Typhi from India

    Science.gov (United States)

    Sharma, Priyanka; Sharma, Sujata; Singh, Tej P.; Kapil, Arti; Kaur, Punit

    2015-01-01

    Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC) of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase. PMID:25962113

  10. Multiresidue determination of quinolone antibacterials in eggs of laying hens by liquid chromatography with fluorescence detection.

    Science.gov (United States)

    Hassouan, M K; Ballesteros, O; Taoufiki, J; Vílchez, J L; Cabrera-Aguilera, M; Navalón, A

    2007-06-01

    An analytical method for the simultaneous determination of seven quinolones (ciprofloxacin, enrofloxacin, danofloxacin, difloxacin, flumequine, oxolinic acid and sarafloxacin) in egg samples of laying hens was developed. Their use is totally prohibited in animals from which eggs are produced for human consumption. Protein precipitation was achieved by addition of acetonitrile and ammonia, removal of acetonitrile with dichloromethane, the quinolones remaining in the basic aqueous extract. The aqueous extract was analysed by liquid chromatography with fluorescence detection (LC-FD). The mobile phase was composed of acetonitrile and 10 mM citrate buffer solution of pH 4.5, with an initial composition of acetonitrile-water (12:88, v/v) and using linear gradient elution. Norfloxacin was used as an internal standard. The limits of detection found were 4-12 ng g(-1). These values were lower than the maximum residue limits (MRLs) established by the European Union for these compounds in different tissues of eggs-producing animals.

  11. Structure based in silico analysis of quinolone resistance in clinical isolates of Salmonella Typhi from India.

    Directory of Open Access Journals (Sweden)

    Manoj Kumar

    Full Text Available Enteric fever is a major cause of morbidity in several parts of the Indian subcontinent. The treatment for typhoid fever majorly includes the fluoroquinolone group of antibiotics. Excessive and indiscriminate use of these antibiotics has led to development of acquired resistance in the causative organism Salmonella Typhi. The resistance towards fluoroquinolones is associated with mutations in the target gene of DNA Gyrase. We have estimated the Minimum Inhibitory Concentration (MIC of commonly used fluoroquinolone representatives from three generations, ciprofloxacin, ofloxacin, levofloxacin and moxifloxacin, for 100 clinical isolates of Salmonella Typhi from patients in the Indian subcontinent. The MICs have been found to be in the range of 0.032 to 8 μg/ml. The gene encoding DNA Gyrase was subsequently sequenced and point mutations were observed in DNA Gyrase in the quinolone resistance determining region comprising Ser83Phe/Tyr and Asp87Tyr/Gly. The binding ability of these four fluoroquinolones in the quinolone binding pocket of wild type as well as mutant DNA Gyrase was computationally analyzed by molecular docking to assess their differential binding behaviour. This study has revealed that mutations in DNA Gyrase alter the characteristics of the binding pocket resulting in the loss of crucial molecular interactions and consequently decrease the binding affinity of fluoroquinolones with the target protein. The present study assists in understanding the underlying molecular and structural mechanism for decreased fluoroquinolone susceptibility in clinical isolates as a consequence of mutations in DNA Gyrase.

  12. Genotypic characterization of quinolone resistant-Escherichia coli isolates from retail food in Morocco.

    Science.gov (United States)

    Nayme, Kaotar; Barguigua, Abouddihaj; Bouchrif, Brahim; Karraouan, Bouchra; El Otmani, Fatima; Elmdaghri, Naima; Zerouali, Khalid; Timinouni, Mohammed

    2017-02-01

    This study was conducted to assess the retail food as a possible vehicle for antimicrobial resistant, particularly quinolones resistant and pathogenic Escherichia coli. We determined the prevalence and characteristics of nalidixic acid (Nal) resistant E. coli isolates from diverse retail food samples. In all, 70 (28%) of 250 E. coli isolates studied were Nal-resistant E. coli and 91% of these were multi-drug resistant. Plasmid mediated quinolone resistance genes were identified in 32 isolates, including aac(6')-Ib-cr (n = 16), qnrS1 (n = 11) and qnrB19 (n = 7). Mutations in gyr A and par C genes were detected among 80% of the isolates, and the isolates showed substitution Ser83-Leu and Asp87-Asn in gyrA and Ser80-Ile in parC. In addition, three different gene cassettes were identified (aadA1, aadA7, aac(3)-Id) in 18%. Virulence-associated genes stx1, eae, sfa, hlyA and stx2 were found in six (8%), three (4%), two (3%), three (4%) and three (4%) isolates, respectively. E. coli isolates of phylogenetic group A were dominant (64%, 45/70). Pulsed field gel electrophoresis revealed none epidemiological relationship between these isolates. The results of this work report the higher frequency of Nal-resistant E. coli isolates from Moroccan retail food samples including MDR and pathogenic isolates.

  13. Relative potency of ketamine and S(+)-ketamine in dogs.

    Science.gov (United States)

    Duque, J C; Oleskovicz, N; Guirro, E C B P; Valadão, C A A; Soares, V E

    2008-08-01

    The aim of this study was to determine the relative potency of racemic ketamine and S(+)-ketamine for the hypnotic effect and to evaluate the clinical anesthesia produced by equianesthetic doses of these two substances in dogs. One hundred and eight dogs were allocated in groups R2, R2.5, R3, R6, R9, R12, S2, S2.5, S3, S6, S9, and S12, to receive by intravenous route 2, 2.5, 3, 6, 9, and 12 mg/kg of ketamine or S(+)-ketamine, respectively. A dose-effect curve was drawn with the dose logarithm and the percentage of dogs that presented hypnosis in each group. The curve was used to obtain a linear regression, to determine the effective doses 100 and the potency relationship. In another experimental phase, eight groups of five dogs received 3, 6, 9 and 12 mg/kg of ketamine or S(+)-ketamine to evaluate the periods of latency, hypnosis, and total recovery. The times in which the dogs reached the sternal position, attempted to stand up for the first time, recovered the standing position, and started to walk were also recorded. The hypnotic dose for ketamine was 9.82 +/- 3.02 (6.86-16.5) mg/kg and for S(+)-ketamine was 7.76 +/- 2.17 (5.86-11.5) mg/kg. The time of hypnosis was longer in R3 and the first attempt to stand up occurred early in R6 when compared with S3 and S6 respectively. When R9 (100% of hypnosis with ketamine) and S6 [100% of hypnosis with S(+)-ketamine] were compared (1:1.5 ratio), the time to sternal position (12 +/- 2.5 and 20.2 +/- 5.6 min respectively) and the total recovery time (45 +/- 5.5 and 60.2 +/- 5.2 min respectively) were significantly shorter with S(+)-ketamine. It was concluded that the potency ratio between ketamine and S(+)-ketamine in dogs is smaller than the one reported in other species, and that the dose obtained after a reduction of 50%, as usually performed in humans, would not be enough to obtain equianesthetic effects in dogs.

  14. Relative potencies and combination effects of steroidal estrogens in fish.

    Science.gov (United States)

    Thorpe, Karen L; Cummings, Rob I; Hutchinson, Thomas H; Scholze, Martin; Brighty, Geoff; Sumpter, John P; Tyler, Charles R

    2003-03-15

    The natural steroids estradiol-17beta (E2) and estrone (E1) and the synthetic steroid ethynylestradiol-17alpha (EE2) have frequently been measured in waters receiving domestic effluents. All of these steroids bind to the estrogen receptor(s) and have been shown to elicit a range of estrogenic responses in fish at environmentally relevant concentrations. At present, however, no relative potency estimates have been derived for either the individual steroidal estrogens or their mixtures in vivo. In this study the estrogenic activity of E2, E1, and EE2, and the combination effects of a mixture of E2 and EE2 (equi-potent fixed-ratio mixture), were assessed using vitellogenin induction in a 14-day in vivo juvenile rainbow trout screening assay. Median effective concentrations, relative to E2, for induction of vitellogenin were determined from the concentration-response curves and the relative estrogenic potencies of each of the test chemicals calculated. Median effective concentrations were between 19 and 26 ng L(-1) for E2, 60 ng L(-1) for E1, and between 0.95 and 1.8 ng L(-1) for EE2, implying that EE2 was approximately 11 to 27 times more potent than E2, while E2 was 2.3 to 3.2 times more potent than E1. The median effective concentration, relative to E2, for the binary mixture of E2 and EE2 was 15 ng L(-1) (comprising 14.4 ng L(-1) E2 and 0.6 ng L(-1) EE2). Using the model of concentration addition it was shown that this activity of the binary mixture could be predicted from the activity of the individual chemicals. The ability of each individual steroid to contribute to the overall effect of a mixture, even at individual no-effect concentrations, combined with the high estrogenic potency of the steroids, particularly the synthetic steroid EE2, emphasizes the need to consider the total estrogenic load of these chemicals in our waterways.

  15. LM potencies: one of the hidden treasures of the sixth edition of the Organon.

    Science.gov (United States)

    De Schepper, L

    1999-07-01

    50 millesimal (LM) potencies have great advantages for all patients, not just those who are hypersensitive because of their great power to heal without major aggravations. Before discussing their advantages this paper describes what LM potencies are, and how they are administered, then addresses two questions: why do we want to avoid aggravations if most homeopaths look for aggravation to know if the remedy is working? And if LM potencies are indeed superior, why are they still relatively unknown and unused?

  16. Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras.

    Directory of Open Access Journals (Sweden)

    Mingliang Chen

    2015-06-01

    Full Text Available Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis.A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84% in 1965-1973 to serogroup A CC1 (58% in 1974-1985, then to serogroup C or B CC4821 (62% in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37 in 2005-2013 (p < 0.001. Among the ciprofloxacin-nonsusceptible isolates, 87% (27/31 were assigned to either CC4821 (n = 20 or CC5 (n = 7. The two predominant ciprofloxacin-resistant clones were designated ChinaCC4821-R1-C/B and ChinaCC5-R14-A. The ChinaCC4821-R1-C/B clone acquired ciprofloxacin resistance by a point mutation, and was present in 52% (16/31 of the ciprofloxacin-nonsusceptible disease isolates. The ChinaCC5-R14-A clone acquired ciprofloxacin resistance by horizontal gene transfer, and was found in 23% (7/31 of the ciprofloxacin-nonsusceptible disease isolates. The ciprofloxacin nonsusceptibility rate was 47% (7/15 among isolates from asymptomatic carriers, and nonsusceptibility was associated with diverse multi-locus sequence typing profiles and pulsed-field gel electrophoresis patterns. As detected after 2005, ciprofloxacin-nonsusceptible strains were shared between some of the patients and their close contacts. A limitation of this study is that isolates from 1986-2004 were not available

  17. Antibacterial potency of methanol extracts of lower plants

    Institute of Scientific and Technical Information of China (English)

    OJO O.O.; AJAYI A.O.; ANIBIJUWON I.I.

    2007-01-01

    Antibacterial potency of methanol extracts of three green lower plants, Pneumatopteris afra, Platycerium bifurcatum and Nephrolepsis bisserata was determined using agar dilution method on clinical strains of Escherichia coli, Staphylococcus aureus, Klebsiella spp. and Salmomelia typhi. Antibacterial activities were observed at concentrations of 12.5, 25.0, 50.0 and 100.0 μg/ml. Their minimum inhibitory concentrations ranged from 12.5~100 μg/ml. Extracts ofP. afra and P. bifurcatum were most active. Antibacterial activities observed with N. bisserata were less pronounced with no detectable activity at extract concentrations of 12.5 and 25.0 μg/ml. E. coli, together with S. aureus appeared to be the most susceptible of the test bacteria while Klebsiella spp. was least sensitive. The significance of our findings is discussed.

  18. Increasing the potency of a cytotoxin with an arginine graft.

    Science.gov (United States)

    Fuchs, Stephen M; Rutkoski, Thomas J; Kung, Vanessa M; Groeschl, Ryan T; Raines, Ronald T

    2007-10-01

    Variants and homologs of bovine pancreatic ribonuclease (RNase A) can exhibit cytotoxic activity. This toxicity relies on cellular internalization of the enzyme. Residues Glu49 and Asp53 form an anionic patch on the surface of RNase A. We find that replacing these two residues with arginine does not affect catalytic activity or affinity for the cytosolic ribonuclease inhibitor (RI) protein. This 'arginine graft' does, however, increase toxicity towards human cancer cells. Appending a nonaarginine domain to this cationic variant results in an additional increase in cytotoxicity, providing one of the most cytotoxic known variants of RNase A. These findings correlate the potency of a ribonuclease with its deliverance of ribonucleolytic activity to the cytosol, and indicate a rational means to enhance the efficacy of ribonucleases and other cytotoxic proteins.

  19. Enantiomers of a nonylphenol isomer: absolute configurations and estrogenic potencies.

    Science.gov (United States)

    Zhang, Haifeng; Oppel, Iris M; Spiteller, Michael; Guenther, Klaus; Boehmler, Gabriele; Zuehlke, Sebastian

    2009-02-01

    Enantiomers of 4-(1,1,2-trimethylhexyl)phenol, a chiral isomer of the endocrine disrupting chemical nonylphenol, have been resolved and isolated by preparative chiral HPLC. The absolute configurations of the enantiomers were then determined by an X-ray crystallographic study of the (-)-camphanoyl derivative of the first eluted enantiomer NP(35)E1. The first enantiomer (NP(35)E1) and the second enantiomer (NP(35)E2) eluted were found to have the S and R absolute configurations, respectively. The estrogenic potencies of the S and R enantiomers were tested by the E-screen assay. A slight difference was observed in the relative proliferative effect between the S enantiomer and R enantiomer in the E-screen assay.

  20. Quinolone- and ß-lactam-resistance in Escherichia coli from Danish and Italian broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne

    Frederiksberg C, Denmark 2Dipartimento di Sanità Pubblica Veterinaria e Patologia Animale, Facoltà di Medicina Veterinaria, Università di Bologna, 40064 Ozzano Emilia (BO), Italy   The prevalence of quinolone- and ß-lactam-resistant E. coli was investigated among broiler flocks in Denmark and Italy. In Denmark...

  1. Studies on the antagonistic action between chloramphenicol and quinolones with presence of bovine serum albumin by fluorescence spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Liu Baosheng, E-mail: lbs@hbu.edu.c [Key Laboratory of Medical Chemistry and Molecular Diagnosis, Ministry of Education, Center of Physics and Chemistry, Hebei University, Baoding 071002 (China); Zhao Fengli; Xue Chunli; Wang Jing; Lu Yunkai [Key Laboratory of Medical Chemistry and Molecular Diagnosis, Ministry of Education, Center of Physics and Chemistry, Hebei University, Baoding 071002 (China)

    2010-05-15

    Chloramphenicol (CHL) and quinolone drugs like ofloxacin (OFLX), lomefloxacin (LMX) and ciprofloxacin (CPFX) can all quench the fluorescence of bovine serum albumin (BSA) in the aqueous solution of pH=7.40. This quenching effect becomes more significant when CHL and quinolone drugs coexist. Based on this, further studies on the interactions between CHL and quinolone drugs using fluorescence spectrum are established. The results showed that the interaction between the drugs would increase the binding constant and binding stability of the drug and protein, thus reducing the amount of drugs transported to their targets. Therefore, free drug concentration at targets would decrease, reducing the efficacy of the drugs. It indicated that there exists antagonistic action between drugs. The results also showed that the quenching mechanism of BSA by the drugs is a static procedure. The number of binding sites is 1 in various systems. Due to the existence of the antagonistic action between drugs, the binding distance r is reduced. Studies utilizing synchronous spectra showed that the antagonistic action between the drugs would affect the conformation of BSA, making protein molecules extend and hydrophobic decrease. The order of antagonistic action between CHL and quinolone drugs is: CPFX>OFLX>LMX with presence of BSA.

  2. Analysis of the gyrA gene of clinical Yersinia ruckeri isolates with reduced susceptibility to quinolones.

    Science.gov (United States)

    Gibello, Alicia; Porrero, M Concepción; Blanco, M Mar; Vela, Ana I; Liébana, Pilar; Moreno, Miguel A; Fernández-Garayzábal, José F; Domínguez, Lucas

    2004-01-01

    Antimicrobial susceptibility of seven clinical strains of Yersinia ruckeri representative of those isolated between 1994 and 2002 from a fish farm with endemic enteric redmouth disease was studied. All isolates displayed indistinguishable pulsed-field gel electrophoresis restriction patterns, indicating that they represented a single strain. However, considering both inhibition zone diameters (IZD) and MICs, the isolates recovered in 2001-2002 formed a separate cluster with lower levels of susceptibility to all the quinolones tested, especially nalidixic acid (NA) and oxolinic acid (OA), compared with the isolates recovered between 1994 and 1998. Analysis of the PCR product of the quinolone resistance-determining region of the gyrA gene from clinical isolates of Y. ruckeri with reduced susceptibility to OA and NA revealed a single amino acid substitution, Ser-83 to Arg-83 (Escherichia coli numbering). Identical substitution was observed in induced OA-resistant mutant strains, which displayed IZD and MICs of quinolones similar to those of the clinical isolates of Y. ruckeri with reduced susceptibility to these antimicrobial agents. These data indicate in that for Y. ruckeri, the substitution of Ser by Arg at position 83 of the gyrA gene is associated with reduced susceptibility to quinolones.

  3. Risk factors for quinolone-resistant Escherichia coli in feces from preweaned dairy calves and postpartum dairy cows.

    Science.gov (United States)

    Duse, Anna; Waller, Karin Persson; Emanuelson, Ulf; Unnerstad, Helle Ericsson; Persson, Ylva; Bengtsson, Björn

    2015-09-01

    Quinolone resistance may emerge in gut bacteria (e.g., in Escherichia coli) of animals. Such bacteria could cause infections in the animal itself or be transmitted to humans via the food chain. Quinolone resistance is also observed in fecal E. coli of healthy dairy cattle, but the prevalence varies between farms, not solely as a result of varying degree of fluoroquinolone exposure. The objective of this study was to identify risk factors for the fecal shedding of quinolone-resistant E. coli (QREC) from dairy calves and postpartum cows. Rectal swabs from 15 preweaned calves and 5 postpartum cows per farm were collected on 23 Swedish dairy farms to determine the prevalence of QREC. Risk factors for the shedding of QREC were investigated using multivariable statistical models. Quinolone-resistant E. coli were found on all but one farm. Factors associated with QREC shedding by calves were being younger than 18 d, being fed milk from cows treated with antimicrobials, recent use of fluoroquinolones in the herd, carriage of QREC by postpartum cows, and using the calving area never or rarely as a sick pen compared with often. Factors associated with QREC shedding by cows were calving in group pens or freestalls compared with single pens or tiestalls, purchasing cattle, sharing animal transports with other farmers, and poor farm hygiene. Proper biosecurity and improved hygiene, as well as minimizing fluoroquinolone exposure and waste milk feeding, may be important factors to reduce the burden of QREC on dairy farms.

  4. Progress in research on quinolone antibacterials%喹诺酮类抗菌药物研究新进展

    Institute of Scientific and Technical Information of China (English)

    蒋晓磊; 崔玉彬; 曹胜华

    2011-01-01

    This article has reviewed progress in research on quinolone antibacterials in recent years,which consisted of newly launched products, agents in clinical trials and future development of this kind of drugs. It focused on some clinical promising candidates. Among these drugs, delafloxacin would be the most potential candidate.Moreover it introduced new fields of the future development, including modifying side chain, quinolone-like compounds, antibacterial quinolone hybrids and anti-TB quinolone-drug conjugates.%本文简述了喹诺酮类药物近几年的研究进展,分为上市药物、临床试验药物和未来发展趋势三部分,对目前处于临床研究阶段的药物做了重点讲述,其中delafloxacin是最有希望的喹诺酮类候选药物,同时介绍了喹诺酮类抗菌药物的未来发展方向,即侧链修饰、喹诺酮类似物、喹诺酮杂合物和TB药物与喹诺酮扼合物.

  5. Rational use of quinolones antibiotics%合理应用喹诺酮类抗菌药物

    Institute of Scientific and Technical Information of China (English)

    宋惠珠

    2011-01-01

    目的 了解喹诺酮类抗菌药物的作用机制,不良反应及使用时的注意事项. 方法 对喹诺酮类抗菌药物在临床使用中的注意事项及所涉及的不良反应进行汇总. 结果 随着临床使用喹诺酮类抗菌药物的增加,药物的不良反应也随着上升,其不良反应发生率<2.0%,肾损害的发生率为0.9%~4.3%. 结论 在广泛应用喹诺酮类抗菌药物的同时,要更多地关注其安全性.%OBJECTIVE To understand the mechanism of quinolones, adverse reactions and precautions when using.METHODS The precautions of quinolones in clinical use and the adverse reactions involved were aggregated.RESULTS With the increased clinical use of quinolones, the incidence of adverse drug reactions was increased more than <2.0%. CONCLUSION In the widely use of quinolones antibiotics, their safety should be more concerned about.

  6. Distribution and risk assessment of quinolone antibiotics in the soils from organic vegetable farms of a subtropical city, Southern China.

    Science.gov (United States)

    Wu, Xiao-Lian; Xiang, Lei; Yan, Qing-Yun; Jiang, Yuan-Neng; Li, Yan-Wen; Huang, Xian-Pei; Li, Hui; Cai, Quan-Ying; Mo, Ce-Hui

    2014-07-15

    Organic fertilizer or manure containing antibiotics has been widely used in organic farms, but the distribution and potential impacts of antibiotics to the local environment are not well understood. In this study, four quinolone antibiotics in soil samples (n=69) from five organic vegetable farms in a subtropical city, Southern China, were analyzed using high performance liquid chromatography-tandem mass spectrometry. Our results indicated that quinolone compounds were ubiquitous in soil samples (detection frequency>97% for all compounds), and their concentrations ranged from not detectable to 42.0 μg/kg. Among the targets, enrofloxacin (ENR) was the dominant compound, followed by ciprofloxacin (CIP) and norfloxacin (NOR). The average total concentrations of four compounds in the soils were affected by vegetable types and species cultivated, decreasing in the order of fruit>rhizome>leaf vegetables. Moreover, the average concentrations of quinolone compounds (except ENR) in open-field soils were higher than those in greenhouse soils. The concentrations of quinolone antibiotics in this study were lower than the ecotoxic effect trigger value (100 μg/kg) proposed by the Veterinary Medicine International Coordination commission. Risk assessment based on the calculated risk quotients indicated that NOR, CIP, and ENR posed mainly medium to low risks to bacteria.

  7. Quinolones control in milk and eggs samples by liquid chromatography using a surfactant-mediated mobile phase.

    Science.gov (United States)

    Rambla-Alegre, M; Collado-Sánchez, M A; Esteve-Romero, J; Carda-Broch, S

    2011-05-01

    Four quinolones (danofloxacin, difloxacin, flumequine and marbofloxacin) were determined in milk and egg samples by a simplified high-performance liquid chromatographic procedure using a micellar mobile phase. No extraction was needed to precipitate the proteins from the matrices since they were solubilised in micelles. The only pretreatment steps required were homogenisation, dilution and filtration before injecting the sample into the chromatographic system. An adequate resolution of the quinolones was achieved by a chemometrics approach where retention was modelled as a first step using the retention factors in only five mobile phases. Afterwards, an optimisation criterion was applied to consider the position and shape of the chromatographic peaks. Analytical separation involved a C18 reversed-phase column, a hybrid micellar mobile phase of 0.05 M sodium dodecyl sulphate, 10% (v/v) butanol and 0.5% (v/v) triethylamine buffered at pH 3 and fluorimetric detection. Quinolones were eluted in less than 15 min without the protein band or other endogenous compounds from the food matrices interfering. The calculated relevant validation parameters, e.g., decision limit (CC(α)), detection capability (CC(β)), repeatability, within-laboratory reproducibility, recoveries and robustness, were acceptable and complied with European Commission Decision 2002/657/EC. Finally, the proposed method was successfully employed in quantifying the four quinolones in spiked egg and milk samples.

  8. Fluorimetric study of the interaction between human serum albumin and quinolones-terbium complex and its application

    Science.gov (United States)

    Wang, Yusheng; Feng, Lin; Jiang, Chongqiu

    2005-10-01

    A highly sensitive spectrofluorimetric method is proposed for determination of human serum albumin (HSA) and some quinolone drugs. Using quinolones-terbium (Tb 3+) complex as a fluorescent probe, in the buffer solution of pH 7.8, HSA can remarkably enhance the fluorescence intensity of the quinolones-Tb 3+ complex at 545 nm and the enhanced fluorescence intensity of Tb 3+ ion is in proportion to the concentration of HSA and quinolone drugs. Optimum conditions for the determination of HSA were also investigated. The linear ranges and limits of detection are 8.0 × 10 -9 to 8.0 × 10 -8 mol L -1, 4.20 × 10 -9 mol L -1 (for HSA); 1.0 × 10 -6 to 4.0 × 10 -6 mol L -1, 1.87 × 10 -8 mol L -1 (for norfloxacin) and 1.0 × 10 -7 to 1.0 × 10 -6 mol L -1, 4.82 × 10 -8 mol L -1 (for enoxacine), respectively. This method is simple, practical and relatively free interference from coexisting substances, as well as much more sensitive than most of the existing assays.

  9. Development of an optical surface plasmon resonance biosensor assay for (fluoro) quinolones in egg, fish, and poultry meat

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Singh, G.; Benrejeb Godefroy, S.; Leivo, J.; Vehniainen, M.; Nielen, M.W.F.; Weigel, S.; Delahaut, P.

    2008-01-01

    The aim of this study was to develop an optical biosensor inhibition immunoassay, based on the surface plasmon resonance (SPR) principle, for use as a screening test for 13 (fluoro)quinolones, including flumequine, used as veterinary drugs in food-producing animals. For this, we immobilised various

  10. Validation of an optical surface plasmon resonance biosensor assay for screening (fluoro)quinolones in egg, fish and poultry

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Weigel, S.; Benrejeb Godefroy, S.; Delahaut, P.

    2009-01-01

    A surface plasmon resonance biosensor immunoassay has been developed for multi-residue determination of 13 (fluoro)quinolone antibiotics in poultry meat, eggs and fish. The following performance characteristics were determined according to the guidelines laid down for screening assay validation in E

  11. Orally bioavailable 6-chloro-7-methoxy-4(1H)-quinolones efficacious against multiple stages of Plasmodium.

    Science.gov (United States)

    Cross, R Matthew; Flanigan, David L; Monastyrskyi, Andrii; LaCrue, Alexis N; Sáenz, Fabián E; Maignan, Jordany R; Mutka, Tina S; White, Karen L; Shackleford, David M; Bathurst, Ian; Fronczek, Frank R; Wojtas, Lukasz; Guida, Wayne C; Charman, Susan A; Burrows, Jeremy N; Kyle, Dennis E; Manetsch, Roman

    2014-11-13

    The continued proliferation of malaria throughout temperate and tropical regions of the world has promoted a push for more efficacious treatments to combat the disease. Unfortunately, more recent remedies such as artemisinin combination therapies have been rendered less effective due to developing parasite resistance, and new drugs are required that target the parasite in the liver to support the disease elimination efforts. Research was initiated to revisit antimalarials developed in the 1940s and 1960s that were deemed unsuitable for use as therapeutic agents as a result of poor understanding of both physicochemical properties and parasitology. Structure-activity and structure-property relationship studies were conducted to generate a set of compounds with the general 6-chloro-7-methoxy-2-methyl-4(1H)-quinolone scaffold which were substituted at the 3-position with a variety of phenyl moieties possessing various properties. Extensive physicochemical evaluation of the quinolone series was carried out to downselect the most promising 4(1H)-quinolones, 7, 62, 66, and 67, which possessed low-nanomolar EC50 values against W2 and TM90-C2B as well as improved microsomal stability. Additionally, in vivo Thompson test results using Plasmodium berghei in mice showed that these 4(1H)-quinolones were efficacious for the reduction of parasitemia at >99% after 6 days.

  12. Quinolone resistance and ESBL/AmpC’s in commensal Escherichia coli in veal calves : prevalence and molecular characterization

    NARCIS (Netherlands)

    Hordijk, J.

    2013-01-01

    In this thesis the prevalence and molecular characteristics of resistance to (fluoro)quinolones and Extended Spectrum Cephalosporins (ESC) in veal calves were described using Escherichia coli as an indicator organism. Ciprofloxacin and nalidixic acid were used as indicator antimicrobials for quinolo

  13. Quinolone resistance and ESBL/AmpC’s in commensal Escherichia coli in veal calves : prevalence and molecular characterization

    NARCIS (Netherlands)

    Hordijk, J.

    2013-01-01

    In this thesis the prevalence and molecular characteristics of resistance to (fluoro)quinolones and Extended Spectrum Cephalosporins (ESC) in veal calves were described using Escherichia coli as an indicator organism. Ciprofloxacin and nalidixic acid were used as indicator antimicrobials for quinolo

  14. Validation of an optical surface plasmon resonance biosensor assay for screening (fluoro)quinolones in egg, fish and poultry

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Weigel, S.; Benrejeb Godefroy, S.; Delahaut, P.

    2009-01-01

    A surface plasmon resonance biosensor immunoassay has been developed for multi-residue determination of 13 (fluoro)quinolone antibiotics in poultry meat, eggs and fish. The following performance characteristics were determined according to the guidelines laid down for screening assay validation in E

  15. Validation of an optical surface plasmon resonance biosensor assay for screening (fluoro)quinolones in egg, fish and poultry

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Weigel, S.; Benrejeb Godefroy, S.; Delahaut, P.

    2009-01-01

    A surface plasmon resonance biosensor immunoassay has been developed for multi-residue determination of 13 (fluoro)quinolone antibiotics in poultry meat, eggs and fish. The following performance characteristics were determined according to the guidelines laid down for screening assay validation in

  16. Development of an optical surface plasmon resonance biosensor assay for (fluoro) quinolones in egg, fish, and poultry meat

    NARCIS (Netherlands)

    Huet, A.C.; Charlier, C.; Singh, G.; Benrejeb Godefroy, S.; Leivo, J.; Vehniainen, M.; Nielen, M.W.F.; Weigel, S.; Delahaut, P.

    2008-01-01

    The aim of this study was to develop an optical biosensor inhibition immunoassay, based on the surface plasmon resonance (SPR) principle, for use as a screening test for 13 (fluoro)quinolones, including flumequine, used as veterinary drugs in food-producing animals. For this, we immobilised various

  17. Detection of mutations in mtrR gene in quinolone resistant strains of N.gonorrhoeae isolated from India

    Directory of Open Access Journals (Sweden)

    S V Kulkarni

    2015-01-01

    Full Text Available Background and Objectives: Emergence of multi-drug resistant Neisseria gonorrhoeae resulting from new genetic mutation is a serious threat in controlling gonorrhea. This study was undertaken to identify and characterise mutations in the mtrR genes in N.gonorrhoeae isolates resistant to six different antibiotics in the quinolone group. Materials and Methods: The Minimum inhibitory concentrations (MIC of five quinolones for 64 N.gonorrhoeae isolates isolated during Jan 2007-Jun 2009 were determined by E-test method. Mutations in MtrR loci were examined by deoxyribonucleic acid (DNA sequencing. Results: The proportion of N.gonorrhoeae strains resistant to anti-microbials was 98.4% for norfloxacin and ofloxacin, 96.8% for enoxacin and ciprofloxacin, 95.3% for lomefloxacin. Thirty-one (48.4% strains showed mutation (single/multiple in mtrR gene. Ten different mutations were observed and Gly-45 → Asp, Tyr-105 → His being the most common observed mutation. Conclusion: This is the first report from India on quinolone resistance mutations in MtrRCDE efflux system in N.gonorrhoeae. In conclusion, the high level of resistance to quinolone and single or multiple mutations in mtrR gene could limit the drug choices for gonorrhoea.

  18. Tubulin acetylation promoting potency and absorption efficacy of deacetylase inhibitors

    Science.gov (United States)

    Mangas-Sanjuan, V; Oláh, J; Gonzalez-Alvarez, I; Lehotzky, A; Tőkési, N; Bermejo, M; Ovádi, J

    2015-01-01

    Background and Purpose Histone deacetylase 6 (HDAC6) and silent information regulator 2 (SIRT2) control the dynamics of the microtubule network via their deacetylase activities. Tubulin polymerization promoting protein (TPPP/p25) enhances microtubule acetylation by its direct binding to HDAC6. Our objective was to characterize the multiple interactions of the deacetylases and to establish the inhibitory potency and the pharmacokinetic features of the deacetylase inhibitors, trichostatin A (TSA) and AGK2. Experimental Approach The interactions of deacetylases with tubulin and TPPP/p25 were quantified by elisa using human recombinant proteins. The effect of inhibitors on the tubulin acetylation was established in HeLa cells transfected with pTPPP and CG-4 cells expressing TPPP/p25 endogenously by celisa (elisa on cells), Western blot and immunofluorescence microscopy. The pharmacokinetic features of the inhibitors were evaluated by in situ kinetic modelling of their intestinal transport in rats. Key Results Deacetylases interact with both tubulin and TPPP/p25, notwithstanding piggy-back binding of HDAC6 or SIRT2 to the TPPP/p25-associated tubulin was established. Much higher inhibitory potency for TSA than for AGK2 was detected in both HeLa and CG-4 cells. Pioneer pharmacokinetic studies revealed passive diffusion and diffusion coupled with secretion for TSA and AGK2 respectively. Both inhibitors exhibited greater permeability than some other well-established drugs. Conclusions and Implications TPPP/p25-directed deacetylase inhibition provides mechanisms for the fine control of the dynamics and stability of the microtubule network. Deacetylase inhibitors with chemical structures similar to TSA and AGK2 appear to be excellent candidates for oral drug absorption. PMID:25257800

  19. Potency of Mahakam Delta in East Kalimantan, Indonesia

    Directory of Open Access Journals (Sweden)

    Zairin Zain

    2014-04-01

    Full Text Available Normal 0 false false false IN X-NONE X-NONE Mahakam Delta is not only utilized for fishery activities but also for several industrial purposes such as coal and oil mining, shipping and timber. The objective of this paper is to provide information in term of the potency of Mahakam Delta located in East Kalimantan province, Indonesia. The study was conducted in Mahakam Delta, East Kalimantan Province, Indonesia. Participatory rural appraisal is a group of methods to collect information in a participatory fashion from rural communities. The method employed in this research was descriptive analysis describing the environmental potency found in Mahakam Delta. Massive conversion of mangrove forest particularly Nypa (Nypa fruticans area into pond has driven conflict among related stakeholders on the utilization of natural resource and land which subsequently impacts on the fish and shrimp source regeneration, loss of ecological functions of mangrove forest for feeding, nursery and spawning ground of fish and other organisms. Besides of fisheries, oil and gas activity also exists in Mahakam Delta. Mahakam Delta is regarded as important area due to the largest producer of oil and gas mining. Thus, oil and gas industry is the most reliable sector that contributes to the economic development of Kutai Kartanegara district. As a resource provider, Mahakam Delta ecosystem provides various resources for livelihoods. As a life-support service provider, Mahakam Delta ecosystem provides habitat and ideal environment to support variety of living kinds. As a convenience provider, Mahakam Delta ecosystem provides unique and interesting recreation site. As a protector from natural disaster, Mahakam Delta ecosystem is able to protect human kinds from natural disaster threatening coastal area.

  20. Anti-Toxoplasma Activities of 24 Quinolones and Fluoroquinolones In Vitro: Prediction of Activity by Molecular Topology and Virtual Computational Techniques

    Science.gov (United States)

    Gozalbes, Rafael; Brun-Pascaud, Monique; Garcia-Domenech, Ramon; Galvez, Jorge; Girard, Pierre-Marie; Doucet, Jean-Pierre; Derouin, Francis

    2000-01-01

    The apicoplast, a plastid-like organelle of Toxoplasma gondii, is thought to be a unique drug target for quinolones. In this study, we assessed the in vitro activity of quinolones against T. gondii and developed new quantitative structure-activity relationship models able to predict this activity. The anti-Toxoplasma activities of 24 quinolones were examined by means of linear discriminant analysis (LDA) using topological indices as structural descriptors. In parallel, in vitro 50% inhibitory concentrations (IC50s) were determined in tissue culture. A multilinear regression (MLR) analysis was then performed to establish a model capable of classifying quinolones by in vitro activity. LDA and MLR analysis were applied to virtual structures to identify the influence of each atom or substituent of the quinolone ring on anti-Toxoplasma activity. LDA predicted that 20 of the 24 quinolones would be active against T. gondii. This was confirmed in vitro for most of the quinolones. Trovafloxacin, grepafloxacin, gatifloxacin, and moxifloxacin were the quinolones most potent against T. gondii, with IC50s of 0.4, 2.4, 4.1, and 5.1 mg/liter, respectively. Using MLR analysis, a good correlation was found between measured and predicted IC50s (r2 = 0.87, cross-validation r2 = 0.74). MLR analysis showed that the carboxylic group at position C-3 of the quinolone ring was not essential for anti-Toxoplasma activity. In contrast, activity was totally dependent on the presence of a fluorine at position C-6 and was enhanced by the presence of a methyl group at C-5 or an azabicyclohexane at C-7. A nucleophilic substituent at C-8 was essential for the activity of gatifloxacin and moxifloxacin. PMID:10991859

  1. Emergence of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae in the Central African Republic: genetic characterization

    Directory of Open Access Journals (Sweden)

    Frank Thierry

    2011-08-01

    Full Text Available Abstract Background Cross-resistance to quinolones and beta-lactams is frequent in Enterobacteriaceae, due to the wide use of these antibiotics clinically and in the food industry. Prescription of one of these categories of antibiotic may consequently select for bacteria resistant to both categories. Genetic mechanisms of resistance may be secondary to a chromosomal mutation located in quinolone resistance determining region of DNA gyrase or topoisomerase IV or to a plasmid acquisition. The insertion sequence ISCR1 is often associated with qnr and may favour its dissemination in Gram-negative bacteria. The aim of this study was to determine the genetic mechanism of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae strains in the Central African Republic. Findings Among seventeen ESBL-producing Enterobacteriaceae isolated from urine, pus or stool between January 2003 and October 2005 in the Central African Republic, nine were resistant to ciprofloxacin (seven from community patients and two from hospitalized patients. The ESBL were previously characterized as CTX-M-15 and SHV-12. Susceptibility to nalidixic acid, norfloxacin and ciprofloxacin, and the minimal inhibitory concentrations of these drugs were determined by disc diffusion and agar dilution methods, respectively. The presence of plasmid-borne ISCR1-qnrA region was determined by PCR and amplicons, if any, were sent for sequencing. Quinolone resistance determining region of DNA gyrase gyrA gene was amplified by PCR and then sequenced for mutation characterization. We found that all CTX-M-producing strains were resistant to the tested quinolones. All the isolates had the same nucleotide mutation at codon 83 of gyrA. Two Escherichia coli strains with the highest MICs were shown to harbour an ISCR1-qnrA1 sequence. This genetic association might favour dissemination of resistance to quinolone and perhaps other antibiotics among Enterobacteriaceae

  2. Implications of binding mode and active site flexibility for inhibitor potency against the salicylate synthase from Mycobacterium tuberculosis.

    Science.gov (United States)

    Chi, Gamma; Manos-Turvey, Alexandra; O'Connor, Patrick D; Johnston, Jodie M; Evans, Genevieve L; Baker, Edward N; Payne, Richard J; Lott, J Shaun; Bulloch, Esther M M

    2012-06-19

    MbtI is the salicylate synthase that catalyzes the first committed step in the synthesis of the iron chelating compound mycobactin in Mycobacterium tuberculosis. We previously developed a series of aromatic inhibitors against MbtI based on the reaction intermediate for this enzyme, isochorismate. The most potent of these inhibitors had hydrophobic substituents, ranging in size from a methyl to a phenyl group, appended to the terminal alkene of the enolpyruvyl group. These compounds exhibited low micromolar inhibition constants against MbtI and were at least an order of magnitude more potent than the parental compound for the series, which carries a native enolpyruvyl group. In this study, we sought to understand how the substituted enolpyruvyl group confers greater potency, by determining cocrystal structures of MbtI with six inhibitors from the series. A switch in binding mode at the MbtI active site is observed for inhibitors carrying a substituted enolpyruvyl group, relative to the parental compound. Computational studies suggest that the change in binding mode, and higher potency, is due to the effect of the substituents on the conformational landscape of the core inhibitor structure. The crystal structures and fluorescence-based thermal shift assays indicate that substituents larger than a methyl group are accommodated in the MbtI active site through significant but localized flexibility in the peptide backbone. These findings have implications for the design of improved inhibitors of MbtI, as well as other chorismate-utilizing enzymes from this family.

  3. Monte Carlo simulation for evaluation of the efficacy of carbapenems and new quinolones against ESBL-producing Escherichia coli.

    Science.gov (United States)

    Nakamura, Tatsuya; Shimizu, Chihiro; Kasahara, Mayumi; Okuda, Kazuyuki; Nakata, Chiyo; Fujimoto, Hiroko; Okura, Hiroe; Komatsu, Masaru; Shimakawa, Kouichi; Sueyoshi, Noriyuki; Ura, Toshiro; Satoh, Kaori; Toyokawa, Masahiro; Wada, Yasunao; Orita, Tamaki; Kofuku, Tomomi; Yamasaki, Katsutoshi; Sakamoto, Masako; Nishio, Hisaaki; Kinoshita, Shohiro; Takahashi, Hakuo

    2009-02-01

    Extended-spectrum beta-lactamase (ESBL)-producing bacteria are known to be resistant to penicillins, cephalosporins, and monobactams because of their substrate specificity, and these bacteria are sensitive only to a narrow range of antimicrobial agents. The present study was undertaken to evaluate the efficacy of carbapenems and the new quinolones against ESBL-producing Escherichia coli, using a Monte Carlo simulation based on the pharmacokinetic/pharmacodynamic (PK/PD) theory. The time above MIC (TAM, %) served as the PK/PD parameter for carbapenems, with the target level set at 40%. The AUC/MIC served as the PK/PD parameter for the new quinolones, with the target level set at more than 125. In the analysis of drug sensitivity, the MIC50 of all carbapenems other than imipenem was low (0.03 microg/ml), while the MIC50 of the new quinolones was higher (1-2 microg/ml). The probability of achieving the PK/PD target with carba penems after two doses at the usual dose level, as determined by the Monte Carlo simulation, was high for each of the carbapenems tested (99.0% for biapenem, 99.60% for meropenem, and 95.03% for doripenem), except for imipenem. Among the new quinolones, the highest probability of achieving the PK/PD target was obtained with pazufloxacin (42.90%). Thus, the results of the present study have revealed that carbapenems are effective at the regular dose and can be used as the first-choice antibiotics for ESBL-producing E. coli because the resistance ratios for carbapenems are low compared to those of the new quinolones.

  4. Antistaphylococcal activity of DX-619, a new des-F(6)-quinolone, compared to those of other agents.

    Science.gov (United States)

    Bogdanovich, Tatiana; Esel, Duygu; Kelly, Linda M; Bozdogan, Bülent; Credito, Kim; Lin, Gengrong; Smith, Kathy; Ednie, Lois M; Hoellman, Dianne B; Appelbaum, Peter C

    2005-08-01

    The in vitro activity of DX-619, a new des-F(6)-quinolone, was tested against staphylococci and compared to those of other antimicrobials. DX-619 had the lowest MIC ranges/MIC(50)s/MIC(90)s (microg/ml) against 131 Staphylococcus aureus strains (32), and ciprofloxacin (>32/>32). Raised quinolone MICs were associated with mutations in GyrA (S84L) and single or double mutations in GrlA (S80F or Y; E84K, G, or V) in all S. aureus strains tested. A recent vancomycin-resistant S. aureus (VRSA) strain (Hershey) was resistant to available quinolones and was inhibited by DX-619 at 0.25 microg/ml and sitafloxacin at 1.0 microg/ml. Vancomycin (except VRSA), linezolid, ranbezolid, tigecycline, and quinupristin-dalfopristin were active against all strains, and teicoplanin was active against S. aureus but less active against coagulase-negative staphylococci. DX-619 produced resistant mutants with MICs of 1 to >32 microg/ml after 32 microg/ml for ciprofloxacin, sitafloxacin, moxifloxacin, and gatifloxacin. DX-619 and sitafloxacin were also more active than other tested drugs against selected mutants and had the lowest mutation frequencies in single-step resistance selection. DX-619 and sitafloxacin were bactericidal against six quinolone-resistant (including the VRSA) and seven quinolone-susceptible strains tested, whereas gatifloxacin, moxifloxacin, levofloxacin, and ciprofloxacin were bactericidal against 11, 10, 7, and 5 strains at 4x MIC after 24 h, respectively. DX-619 was also bactericidal against one other VRSA strain, five vancomycin-intermediate S. aureus strains, and four vancomycin-intermediate coagulase-negative staphylococci. Linezolid, ranbezolid, and tigecycline were bacteriostatic and quinupristin-dalfopristin, teicoplanin, and vancomycin were bactericidal against two, eight, and nine strains, and daptomycin and oritavancin were rapidly bactericidal against all strains, including the VRSA. DX-619 has potent in vitro activity against staphylococci, including

  5. A function of SmeDEF, the major quinolone resistance determinant of Stenotrophomonas maltophilia, is the colonization of plant roots.

    Science.gov (United States)

    García-León, Guillermo; Hernández, Alvaro; Hernando-Amado, Sara; Alavi, Peyman; Berg, Gabriele; Martínez, José Luis

    2014-08-01

    Quinolones are synthetic antibiotics, and the main cause of resistance to these antimicrobials is mutation of the genes encoding their targets. However, in contrast to the case for other organisms, such mutations have not been found in quinolone-resistant Stenotrophomonas maltophilia isolates, in which overproduction of the SmeDEF efflux pump is a major cause of quinolone resistance. SmeDEF is chromosomally encoded and highly conserved in all studied S. maltophilia strains; it is an ancient element that evolved over millions of years in this species. It thus seems unlikely that its main function would be resistance to quinolones, a family of synthetic antibiotics not present in natural environments until the last few decades. Expression of SmeDEF is tightly controlled by the transcriptional repressor SmeT. Our work shows that plant-produced flavonoids can bind to SmeT, releasing it from smeDEF and smeT operators. Antibiotics extruded by SmeDEF do not impede the binding of SmeT to DNA. The fact that plant-produced flavonoids specifically induce smeDEF expression indicates that they are bona fide effectors regulating expression of this resistance determinant. Expression of efflux pumps is usually downregulated unless their activity is needed. Since smeDEF expression is triggered by plant-produced flavonoids, we reasoned that this efflux pump may have a role in the colonization of plants by S. maltophilia. Our results showed that, indeed, deletion of smeE impairs S. maltophilia colonization of plant roots. Altogether, our results indicate that quinolone resistance is a recent function of SmeDEF and that colonization of plant roots is likely one original function of this efflux pump.

  6. Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II.

    Directory of Open Access Journals (Sweden)

    Rachael E Hawtin

    Full Text Available BACKGROUND: Topoisomerase II is critical for DNA replication, transcription and chromosome segregation and is a well validated target of anti-neoplastic drugs including the anthracyclines and epipodophyllotoxins. However, these drugs are limited by common tumor resistance mechanisms and side-effect profiles. Novel topoisomerase II-targeting agents may benefit patients who prove resistant to currently available topoisomerase II-targeting drugs or encounter unacceptable toxicities. Voreloxin is an anticancer quinolone derivative, a chemical scaffold not used previously for cancer treatment. Voreloxin is completing Phase 2 clinical trials in acute myeloid leukemia and platinum-resistant ovarian cancer. This study defined voreloxin's anticancer mechanism of action as a critical component of rational clinical development informed by translational research. METHODS/PRINCIPAL FINDINGS: Biochemical and cell-based studies established that voreloxin intercalates DNA and poisons topoisomerase II, causing DNA double-strand breaks, G2 arrest, and apoptosis. Voreloxin is differentiated both structurally and mechanistically from other topoisomerase II poisons currently in use as chemotherapeutics. In cell-based studies, voreloxin poisoned topoisomerase II and caused dose-dependent, site-selective DNA fragmentation analogous to that of quinolone antibacterials in prokaryotes; in contrast etoposide, the nonintercalating epipodophyllotoxin topoisomerase II poison, caused extensive DNA fragmentation. Etoposide's activity was highly dependent on topoisomerase II while voreloxin and the intercalating anthracycline topoisomerase II poison, doxorubicin, had comparable dependence on this enzyme for inducing G2 arrest. Mechanistic interrogation with voreloxin analogs revealed that intercalation is required for voreloxin's activity; a nonintercalating analog did not inhibit proliferation or induce G2 arrest, while an analog with enhanced intercalation was 9.5-fold more

  7. Sexual Function and the Use of Medical Devices or Drugs to Optimize Potency After Prostate Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Whaley, J. Taylor; Levy, Lawrence B. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Swanson, David A. [Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Pugh, Thomas J. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Kudchadker, Rajat J.; Bruno, Teresa L. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, TX (United States); Frank, Steven J., E-mail: sjfrank@mdnaderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX (United States)

    2012-04-01

    Purpose: Prospective evaluation of sexual outcomes after prostate brachytherapy with iodine-125 seeds as monotherapy at a tertiary cancer care center. Methods and Materials: Subjects were 129 men with prostate cancer with I-125 seed implants (prescribed dose, 145 Gy) without supplemental hormonal or external beam radiation therapy. Sexual function, potency, and bother were prospectively assessed at baseline and at 1, 4, 8, and 12 months using validated quality-of-life self-assessment surveys. Postimplant dosimetry values, including dose to 10% of the penile bulb (D10), D20, D33, D50, D75, D90, and penile volume receiving 100% of the prescribed dose (V100) were calculated. Results: At baseline, 56% of patients recorded having optimal erections; at 1 year, 62% of patients with baseline erectile function maintained optimal potency, 58% of whom with medically prescribed sexual aids or drugs. Variables associated with pretreatment-to-posttreatment decline in potency were time after implant (p = 0.04) and age (p = 0.01). Decline in urinary function may have been related to decline in potency. At 1 year, 69% of potent patients younger than 70 years maintained optimal potency, whereas 31% of patients older than 70 maintained optimal potency (p = 0.02). Diabetes was related to a decline in potency (p = 0.05), but neither smoking nor hypertension were. For patients with optimal potency at baseline, mean sexual bother scores had declined significantly at 1 year (p < 0.01). Sexual potency, sexual function, and sexual bother scores failed to correlate with any dosimetric variable tested. Conclusions: Erections firm enough for intercourse can be achieved at 1 year after treatment, but most men will require medical aids to optimize potency. Although younger men were better able to maintain erections firm enough for intercourse than older men, there was no correlation between potency, sexual function, or sexual bother and penile bulb dosimetry.

  8. Resistance patterns to beta-lactams and quinolones in clinical isolates of bacteria from Cuban hospitals.

    Science.gov (United States)

    Gonzáles, I; Niebla, A; Vallin, C

    1995-01-01

    The resistance patterns to 26 beta-lactams and 8 quinolones of clinical isolates from Cuban hospitals were evaluated using the disk susceptibility test, according to the NCCLS guidelines (1992). The genera studied were Escherichia sp (320), Enterobacter sp (10), Klebsiella sp (90), Proteus sp (10), Pseudomonas sp (90), Serratia sp (20), and Staphylococcus sp (80). Higher resistance to beta-lactams was observed in the genera Pseudomonas, Escherichia and Klebsiella. For fluoroquinolones we found no significant resistance, with the exception of the genus Klebsiella. The most effective antibiotics were cephalosporins of the second and third generations, fluoroquinolones, and non-classical beta-lactams (cephamycins, moxalactam and monobactams). On the contrary, a pronounced resistance was found to penicillin, oxacillin, ticarcillin, ampicillin, methicillin, nalidixic acid and cinoxacin. These resistance patterns correspond to the high consumption of these antibiotics throughout the country.

  9. Capillary electrophoresis with electrochemiluminescence detection for the analysis of quinolone drugs and pharmacokinetics study

    Institute of Scientific and Technical Information of China (English)

    Yan Ming Liu; Jun Tao Cao; Hui Wang

    2008-01-01

    A novel method for the determination of two quinolone drugs norfloxacin (NOR) and levofloxacin (LVX) was described by capillary electrophoresis with electrochemiluminescence detection. The good relationship (r ≥ 0.9991) between peak area and concentration of analytes was established over two orders of magnitude. The limits of detection (LOD, S/N = 3) in standard solution are 4.8 × 10-7 mol/L for NOR and 6.4 × 10-7 mol/L for LVX, respectively. The limits of quantitation (LOQ, S/N = 10) in real human urine samples are 1.2 × 10-6 mol/L for NOR and 1.4 × 10-6 mol/L for LVX, respectively. The present method was successfully applied to the determination of NOR and LVX in human urine and the study of pharmacokinetics of NOR.

  10. International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive-capacity

    NARCIS (Netherlands)

    Teunis, M.A.T.; Spiekstra, S.W.; Smits, M.; Adriaens, E.; Eltze, T.; Galbiati, V.; Krul, C.A.M.; Landsiedel, R.; Pieters, R.; Reinders, J.; Roggen, E.; Corsini, E.; Gibbs, S.

    2014-01-01

    This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50%

  11. 76 FR 9028 - Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products; Availability

    Science.gov (United States)

    2011-02-16

    ... Industry: Potency Tests for Cellular and Gene Therapy Products'' dated January 2011. The guidance document provides manufacturers of cellular and gene therapy (CGT) products with recommendations for developing... document entitled ``Guidance for Industry: Potency Tests for Cellular and Gene Therapy Products''...

  12. International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive capacity

    NARCIS (Netherlands)

    Teunis, M.A.T.; Spiekstra, S.W.; Smits, M.; Adriaens, E.; Eltze, T.; Galbiati, V.; Krul, C.; Landsiedel, R.; Pieters, R.; Reinders, J.; Roggen, E.; Corsini, E.; Gibbs, S.

    2014-01-01

    This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50%

  13. International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive capacity

    NARCIS (Netherlands)

    Teunis, M.A.T.; Spiekstra, S.W.; Smits, M.; Adriaens, E.; Eltze, T.; Galbiati, V.; Krul, C.; Landsiedel, R.; Pieters, R.; Reinders, J.; Roggen, E.; Corsini, E.; Gibbs, S.

    2014-01-01

    This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50%

  14. In vitro profiling of the endocrine-disrupting potency of brominated flame retardants

    NARCIS (Netherlands)

    Hamers, T.H.M.; Kamstra, J.H.; Sonneveld, E.; Murk, A.J.; Kester, M.H.A.; Andersson, P.L.; Legler, J.; Brouwer, A.

    2006-01-01

    Over the last years, increasing evidence has become available that some brominated flame retardants (BFRs) may have endocrine disrupting (ED) potencies. The goal of the current study was to perform a systematic in vitro screening of the ED potencies of BFRs (1) to elucidate possible modes of action

  15. Fate and antibacterial potency of anticoccidial drugs and their main abiotic degradation products

    DEFF Research Database (Denmark)

    Hansen, Martin; Krogh, Kristine A; Brandt, Asbjørn

    2009-01-01

    )). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC(50)-values. The influence of pH, temperature, oxygen concentration and light...

  16. In vitro profiling of the endocrine-disrupting potency of brominated flame retardants

    NARCIS (Netherlands)

    Hamers, T.H.M.; Kamstra, J.H.; Sonneveld, E.; Murk, A.J.; Kester, M.H.A.; Andersson, P.L.; Legler, J.; Brouwer, A.

    2006-01-01

    Over the last years, increasing evidence has become available that some brominated flame retardants (BFRs) may have endocrine disrupting (ED) potencies. The goal of the current study was to perform a systematic in vitro screening of the ED potencies of BFRs (1) to elucidate possible modes of action

  17. International ring trial of the epidermal equivalent sensitizer potency assay: reproducibility and predictive-capacity

    NARCIS (Netherlands)

    Teunis, M.A.T.; Spiekstra, S.W.; Smits, M.; Adriaens, E.; Eltze, T.; Galbiati, V.; Krul, C.A.M.; Landsiedel, R.; Pieters, R.; Reinders, J.; Roggen, E.; Corsini, E.; Gibbs, S.

    2014-01-01

    This study describes the international ring trial of the epidermal-equivalent (EE) sensitizer potency assay. This assay does not distinguish a sensitizer from a non-sensitizer, but may classify known skin sensitizers according to their potency. It assesses the chemical concentration resulting in 50%

  18. Vasoconstriction Potency Induced by Aminoamide Local Anesthetics Correlates with Lipid Solubility

    Directory of Open Access Journals (Sweden)

    Hui-Jin Sung

    2012-01-01

    Full Text Available Aminoamide local anesthetics induce vasoconstriction in vivo and in vitro. The goals of this in vitro study were to investigate the potency of local anesthetic-induced vasoconstriction and to identify the physicochemical property (octanol/buffer partition coefficient, pKa, molecular weight, or potency of local anesthetics that determines their potency in inducing isolated rat aortic ring contraction. Cumulative concentration-response curves to local anesthetics (levobupivacaine, ropivacaine, lidocaine, and mepivacaine were obtained from isolated rat aorta. Regression analyses were performed to determine the relationship between the reported physicochemical properties of local anesthetics and the local anesthetic concentration that produced 50% (ED50 of the local anesthetic-induced maximum vasoconstriction. We determined the order of potency (ED50 of vasoconstriction among local anesthetics to be levobupivacaine > ropivacaine > lidocaine > mepivacaine. The relative importance of the independent variables that affect the vasoconstriction potency is octanol/buffer partition coefficient > potency > pKa > molecular weight. The ED50 in endothelium-denuded aorta negatively correlated with the octanol/buffer partition coefficient of local anesthetics (r2=0.9563; P<0.001. The potency of the vasoconstriction in the endothelium-denuded aorta induced by local anesthetics is determined primarily by lipid solubility and, in part, by other physicochemical properties including potency and pKa.

  19. Plasmid-mediated quinolone resistance among extended spectrum beta lactase producing Enterobacteriaceae from bloodstream infections.

    Science.gov (United States)

    Domokos, Judit; Kristóf, Katalin; Szabó, Dóra

    2016-09-01

    The purpose of this study was to determine prevalence and molecular characterization of plasmid-mediated quinolone resistance (PMQR) genes [qnrA, qnrB, qnrC, qnrD, qnrS, aac(6')-Ib-cr, qepA, and oqxAB] among extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella spp. isolates from bloodcultures in Hungary. A total of 103 isolates were tested for quinolone susceptibility by microdilution method and PMQR genes were detected by polymerase chain reaction. About 40 ESBL-producing E. coli (39%) and 50 ESBL-producing Klebsiella spp. strains (48%) were resistant to ciprofloxacin; 40 ESBL-producing E. coli (39%) and 47 ESBL-producing Klebsiella spp. strains (45%) were resistant to levofloxacin; and 88 strains including 40 ESBL-producing E. coli (39%) and 48 (47%) ESBL-producing Klebsiella spp. were resistant to moxifloxacin. Among the 103 ESBL-producing isolates, 77 (75%) isolates (30 E. coli and 47 Klebsiella spp.) harbored PMQR genes. The most commonly detected gene was aac(6')-Ib-cr (65%). The occurrence of qnrS gene was 6%. Interestingly, qnrA, qnrB, qnrC, qnrD, and qepA were not found in any isolates. Among 77 PMQR-positive isolates, 27 (35.1%) and 1 (1.3%) carried two and three different PMQR genes, respectively. Only Klebsiella spp. harbored more than one PMQR genes. Observing prevalence of PMQR genes in the last 8 years, the increasing incidence of aac(6')-Ib-cr and oqxAB can be seen. Our results highlight high frequency of PMQR genes among ESBL-producing Klebsiella pneumoniae and E. coli isolates with an increasing dynamics in Hungary.

  20. QUINOLONE- AND ETA-LACTAM- RESISTANCE IN Escherichia coli FROM DANISH AND ITALIAN BROILER FLOCKS

    Directory of Open Access Journals (Sweden)

    M. Trevisani

    2009-03-01

    Full Text Available The prevalence of quinolone- and -lactam-resistant E. coli was investigated among healthy broiler flocks in Denmark and Italy. In Denmark, sock samples were collected from 10 parent flocks and 10 offspring flocks, according to the procedure currently used for the surveillance of Salmonella in the EU. Samples were enriched in McConkey broth and streaked on McConkey agar plates added with nalidixic acid (32 g/ml, ciprofloxacin (2 g/ml, ampicillin (32 g/ml, cefotaxime (2 g/ml or ceftiofur (8 g/ml. The -glucuronidase test was performed for verification of presumptive E. coli. The same methods were used to analyse sock samples collected from 6 Italian broiler flocks. PCR with primers for the CTX-M-type extended-spectrum -lactamases (ESBLs was performed on cephalosporin-resistant isolates. While resistance to ampicillin and nalidixic acid was widespread in both countries, resistance to ciprofloxacin and cephalosporins was more common among Italian flocks. In Denmark, ciprofloxacin resistance was only detected in 1 parent flock without any history of quinolone usage and none of the flocks was positive for cephalosporin-resistant E. coli. In Italy, resistance to ciprofloxacin was detected in all flocks and resistance to ceftiofur and cefotaxime were detected in 5 flocks. Primers specific for the CTX-M-type ESBLs generated PCR amplicons from isolates from 3 of these flocks. In industrialized countries, the poultry production system is highly standardized, and therefore comparable. However, the use of broad-spectrum antimicrobials is particularly limited in Danish poultry production. Accordingly, the results of this study could reflect the different policies in antimicrobial usage between the two countries.

  1. Building-related symptoms and inflammatory potency of dust from office buildings

    DEFF Research Database (Denmark)

    Allermann, Leila; Pejtersen, Jan; Gunnarsen, Lars Bo

    2007-01-01

    Abstract The aim was to investigate the association between building-related symptoms (BRS) in office buildings and the inflammatory potency of dust (PD). Furthermore, the association between dust potency and various building characteristics was investigated. Occupants of 22 office buildings...... received a retrospective questionnaire about BRS (2301 respondents). Dust was collected from groups of offices and building characteristics were recorded. The potency of a dust sample to induce interleukin-8 (IL-8) secretion from the lung epithelial cell line A549 was measured as the slope of the initial...... linear part of the concentration- response curve. Symptoms of the central nervous system (CNS) were associated with the potency of surface dust (OR ¼ 1.4). This association may be due to an association between an index of CNS symptoms and dust potency in offices of 1-6 occupants (OR ¼ 1.5). No single...

  2. Building-related symptoms and inflammatory potency of dust from office buildings

    DEFF Research Database (Denmark)

    Allermann, L; Pejtersen, J; Gunnarsen, L

    2007-01-01

    UNLABELLED: The aim was to investigate the association between building-related symptoms (BRS) in office buildings and the inflammatory potency of dust (PD). Furthermore, the association between dust potency and various building characteristics was investigated. Occupants of 22 office buildings...... received a retrospective questionnaire about BRS (2301 respondents). Dust was collected from groups of offices and building characteristics were recorded. The potency of a dust sample to induce interleukin-8 (IL-8) secretion from the lung epithelial cell line A549 was measured as the slope of the initial...... linear part of the concentration-response curve. Symptoms of the central nervous system (CNS) were associated with the potency of surface dust (OR = 1.4). This association may be due to an association between an index of CNS symptoms and dust potency in offices of 1-6 occupants (OR = 1.5). No single...

  3. Building-related symptoms and inflammatory potency of dust from office buildings

    DEFF Research Database (Denmark)

    Allermann, Leila; Pejtersen, Jan; Gunnarsen, Lars Bo

    2007-01-01

    Abstract The aim was to investigate the association between building-related symptoms (BRS) in office buildings and the inflammatory potency of dust (PD). Furthermore, the association between dust potency and various building characteristics was investigated. Occupants of 22 office buildings...... linear part of the concentration- response curve. Symptoms of the central nervous system (CNS) were associated with the potency of surface dust (OR ¼ 1.4). This association may be due to an association between an index of CNS symptoms and dust potency in offices of 1-6 occupants (OR ¼ 1.5). No single...... symptoms correlated with the potency of surface dust. The PD was not related to single building factors. The inflammatory PD may be used as an integrated proxy measure of biologically active compounds in dust, reflecting health relevant properties of the dust....

  4. Coexistence of blaOXA-23 with armA in quinolone-resistant Acinetobacter baumannii from a Chinese university hospital.

    Science.gov (United States)

    Shen, Min; Luan, Guangxin; Wang, Yanhong; Chang, Yaowen; Zhang, Chi; Yang, Jingni; Deng, Shanshan; Ling, Baodong; Jia, Xu

    2016-03-01

    A total of 101 Acinetobacter baumannii isolates were collected to determine the mechanisms of quinolone resistance and investigate the occurrence of carbapenem and high-level aminoglycoside resistance genes among quinolone-resistant strains. Among 77 quinolone-resistant A. baumannii harbored mutations of gyrA and parC, 41 isolates, which belonged to European clone II, had resistance to aminoglycosides and carbapenems due to the expression of armA and acquisition of blaOXA-23. Most of sequence type belonged to clonal complex 92. These results suggested hospital dissemination of multidrug-resistant A. baumannii carrying blaOXA-23, armA, and mutations of quinolone resistance-determining regions in western China.

  5. Prevalence of Plasmid-Mediated Quinolone Resistance Genes among Ciprofloxacin-Nonsusceptible Escherichia coli and Klebsiella pneumoniae Isolated from Blood Cultures in Korea

    Directory of Open Access Journals (Sweden)

    Hee Young Yang

    2014-01-01

    Full Text Available OBJECTIVES:To analyze the prevalence of plasmid-mediated quinolone resistance (PMQR determinants in ciprofloxacin-nonsusceptible Escherichia coli and Klebsiella pneumoniae isolated from patients at a tertiary care hospital in Korea.

  6. GABA receptor subunit composition relative to insecticide potency and selectivity.

    Science.gov (United States)

    Ratra, G S; Casida, J E

    2001-07-01

    Three observations on the 4-[(3)H]propyl-4'-ethynylbicycloorthobenzoate ([(3)H]EBOB) binding site in the gamma-aminobutyric acid (GABA) receptor indicate the specific target for insecticide action in human brain and a possible mechanism for selectivity. First, from published data, alpha-endosulfan, lindane and fipronil compete for the [(3)H]EBOB binding site with affinities of 0.3--7 nM in both human recombinant homooligomeric beta 3 receptors and housefly head membranes. Second, from structure-activity studies, including new data, GABAergic insecticide binding potency on the pentameric receptor formed from the beta 3 subunit correlates well with that on the housefly receptor (r=0.88, n=20). This conserved inhibitor specificity is consistent with known sequence homologies in the housefly GABA receptor and the human GABA(A) receptor beta 3 subunit. Third, as mostly new findings, various combinations of alpha 1, alpha 6, and gamma 2 subunits coexpressed with a beta 1 or beta 3 subunit confer differential insecticide binding sensitivity, particularly to fipronil, indicating that subunit composition is a major factor in insecticide selectivity.

  7. Differential potencies of effector genes in adult Drosophila.

    Science.gov (United States)

    Thum, Andreas S; Knapek, Stephan; Rister, Jens; Dierichs-Schmitt, Eva; Heisenberg, Martin; Tanimoto, Hiromu

    2006-09-10

    The GAL4/UAS gene expression system in Drosophila has been crucial in revealing the behavioral significance of neural circuits. Transgene products that block neurotransmitter release and induce cell death have been proved to inhibit neural function powerfully. Here we compare the action of the five effector genes shibire(ts1), Tetanus toxin light chain (TNT), reaper, Diphtheria toxin A-chain (DTA), and inwardly rectifying potassium channel (Kir2.1) and show differences in their efficiency depending on the target cells and the timing of induction. Specifically, effectors blocking neuronal transmission or excitability led to adult-induced paralysis more efficiently than those causing cell ablation. We contrasted these differential potencies in adult to their actions during development. Furthermore, we induced TNT expression in the adult mushroom bodies. In contrast to the successful impairment in short-term olfactory memory by shibire(ts1), adult TNT expression in the same set of cells did not lead to any obvious impairment. Altogether, the efficiency of effector genes depends on properties of the targeted neurons. Thus, we conclude that the selection of the appropriate effector gene is critical for evaluating the function of neural circuits.

  8. A new ELISA for determination of potency in snake antivenoms.

    Science.gov (United States)

    Rial, A; Morais, V; Rossi, S; Massaldi, H

    2006-09-15

    A competitive ELISA for potency determination of bothropic equine antivenom was developed and compared to the conventional in vivo ED(50) assay, with the aim of partially substituting the in vivo assay in the monitoring of antivenom immunoglobulin levels. On this purpose, blood samples were taken at different times during and after the immunization protocol of the lot of horses used for production of snake antivenom at the Instituto de Higiene, Uruguay. Both the competitive ELISA and the ED(50) assay were performed on those samples. In addition, a group of five commercial pepsin-digested antivenoms were tested by both methods. A significant (P<0.001) correlation (Pearson's r=0.957) was found between the ELISA titres and the corresponding ED(50) values, indicating that the in vitro test can estimate the neutralizing antibody capacity of the sera as well as the in vivo assay. By means of this new ELISA, it was found that the immunized animals maintained good venom antibody titres, in the order of 20-50% of the maximum achieved, even 10 month after the end of the immunization schedule. The main advantage of our ELISA design is its ability to correctly estimate the neutralization capacity of crude hyperimmune plasma and antivenom sera independently of their antibody composition in terms of whole IgG or F(ab')(2) fragment.

  9. Potency Of Bacteriocin For Animal Health And Food Safety

    Directory of Open Access Journals (Sweden)

    Siti Chotiah

    2013-06-01

    Full Text Available The emergence of antibiotic resistance in many bacteria related to animal and public health stresses the importance of decreasing the use of antibiotics in animal production. The reduction of antibiotic application in livestock can only be achieved if alternative antimicrobial strategies are available. A number of strategies have been explored to control microbial pathogens and to improve growth and feed efficiency in livestock without the use of antibiotics. Bacteriocins have been more extensively studied and proposed as potential alternatives to conventional antibiotics in animal husbandry. Bacteriocins are antimicrobial peptides ribosomally synthesized by many species of Bacteria and some strains of Archaea. In general, bacteriocins just exhibited bactericidal or bacteriostatic activity against other bacteria that are closely related to the producing strain. The main mechanisms of bacteriocin activity vary from pore formation in cytoplasmic membranes to the inhibition of cell wall biosynthesis and enzyme activities (RNAse or DNAse in target cells. The use of bacteriocins in probiotic applications, as preservatives, and most excitingly as alternatives to conventional antibiotics is being broadly explored and studied. This review will describe the bacteriocins potency for animal health and food safety, as well as the results of bacteriocin study that had been conducted in Indonesia.

  10. Antigenotoxic potencies of a lichen species, Evernia prunastri.

    Science.gov (United States)

    Alpsoy, Lokman; Orhan, Furkan; Nardemir, Gokce; Agar, Guleray; Gulluce, Medine; Aslan, Ali

    2015-02-01

    In this article, the genotoxic and antigenotoxic effects of methanol extract of Evernia prunastri (Huds.) Willd. (MEP) were studied using WP2, Ames (TA1535 and TA1537) and sister chromatid exchange (SCE) test systems. The results obtained from bacterial test systems demonstrated that MEP has strong antimutagenic potencies on TA1537 and WP2 strains. The highest inhibition rates for MEP on TA1537 and WP2 strains were 37.70% and 69.70%, respectively. According to the SCE test system, MEP reduced the genotoxic effects of aflatoxin. In order to clarify the mechanism underlying the antigenotoxic effects of MEP, the antioxidants were determined. Cotreatments of 5, 10 and 20 µg/mL concentrations of MEP with aflatoxin B1 decreased the frequencies of SCE and the malondialdehyde level and increased amount of superoxide dismutase, glutathione and glutathione peroxidase which were decreased by aflatoxin. The data obtained from this work have clearly shown that MEP has significant antigenotoxic effects which are thought to be partly due to the antioxidant activities and antioxidant inducing capability of MEP. This is the first report indicating the antigenotoxic activities of MEP against several mutagen agents such as N-methyl-N'-nitro-N-nitrosoguanidine, acridin and aflatoxin. © The Author(s) 2012.

  11. Radioiodination of chicken luteinizing hormone without affecting receptor binding potency

    Energy Technology Data Exchange (ETDEWEB)

    Kikuchi, M.; Ishii, S. (Waseda Univ., Tokyo (Japan))

    1989-12-01

    By improving the currently used lactoperoxidase method, we were able to obtain radioiodinated chicken luteinizing hormone (LH) that shows high specific binding and low nonspecific binding to a crude plasma membrane fraction of testicular cells of the domestic fowl and the Japanese quail, and to the ovarian granulosa cells of the Japanese quail. The change we made from the original method consisted of (1) using chicken LH for radioiodination that was not only highly purified but also retained a high receptor binding potency; (2) controlling the level of incorporation of radioiodine into chicken LH molecules by employing a short reaction time and low temperature; and (3) fractionating radioiodinated chicken LH further by gel filtration using high-performance liquid chromatography. Specific radioactivity of the final {sup 125}I-labeled chicken LH preparation was 14 microCi/micrograms. When specific binding was 12-16%, nonspecific binding was as low as 2-4% in the gonadal receptors. {sup 125}I-Labeled chicken LH was displaced by chicken LH and ovine LH but not by chicken follicle-stimulating hormone. The equilibrium association constant of quail testicular receptor was 3.6 x 10(9) M-1. We concluded that chicken LH radioiodinated by the present method is useful for studies of avian LH receptors.

  12. Potency of Fish Collagen as a Scaffold for Regenerative Medicine

    Directory of Open Access Journals (Sweden)

    Shizuka Yamada

    2014-01-01

    Full Text Available Cells, growth factors, and scaffold are the crucial factors for tissue engineering. Recently, scaffolds consisting of natural polymers, such as collagen and gelatin, bioabsorbable synthetic polymers, such as polylactic acid and polyglycolic acid, and inorganic materials, such as hydroxyapatite, as well as composite materials have been rapidly developed. In particular, collagen is the most promising material for tissue engineering due to its biocompatibility and biodegradability. Collagen contains specific cell adhesion domains, including the arginine-glycine-aspartic acid (RGD motif. After the integrin receptor on the cell surface binds to the RGD motif on the collagen molecule, cell adhesion is actively induced. This interaction contributes to the promotion of cell growth and differentiation and the regulation of various cell functions. However, it is difficult to use a pure collagen scaffold as a tissue engineering material due to its low mechanical strength. In order to make up for this disadvantage, collagen scaffolds are often modified using a cross-linker, such as gamma irradiation and carbodiimide. Taking into account the possibility of zoonosis, a variety of recent reports have been documented using fish collagen scaffolds. We herein review the potency of fish collagen scaffolds as well as associated problems to be addressed for use in regenerative medicine.

  13. Characterization of HmqF, a protein involved in the biosynthesis of unsaturated quinolones produced by Burkholderia thailandensis.

    Science.gov (United States)

    Agarwal, Aparna; Kahyaoglu, Caroline; Hansen, Darren B

    2012-02-28

    The opportunistic pathogen Burkholderia thailandensis produces a number of structurally similar unsaturated quinolones involved in quorum sensing. However, little is known about the biosynthesis of these unsaturated quinolones. In this study, we have characterized the starting point of the biosynthesis of unsaturated quinolone molecules produced in B. thailandensis. We have shown by using in vitro enzymology, liquid chromatography, and mass spectrometry that protein HmqF is involved in the biosynthesis of unsaturated quinolones produced by B. thailandensis. HmqF consists of three domains: an adenylation domain (A domain), a dehydrogenase domain (DH domain), and an acyl carrier domain (ACP). The three domains (A, DH, and ACP) were cloned and expressed individually in Escherichia coli, and their reactivity was studied using high-performance liquid chromatography (HPLC) and mass spectrometry (MS) based assays. Our in vitro studies show that the A domain catalyzes ATP-dependent activation of medium chain (C6-C14) fatty acids without activation by coenzyme A (CoA). Results from competition assays are consistent with decanoic acid being the preferred substrate. Incubation of the ACP domain with 4'-phosphopantetheine transferase and CoA led to the formation of phosphopantetheinylated ACP (Ppant-ACP). In a Ppant ejection assay using tandem MS (MS/MS), a mass consistent with the mass of a cyclic variant of dephosphorylated Ppant was detected. We further demonstrated that Ppant-ACP could be loaded with medium chain fatty acids in the presence of ATP and the A domain. MS analysis was consistent with the formation of Ppant-ACP thiol esters of the fatty acids. MS/MS Ppant ejection experiments confirmed the loss of 2H in samples of fatty acid-loaded Ppant-ACP in the presence of the DH domain. HPLC analysis of benzyl amide ligation products allowed us to conclude that dehydrogenation produced trans-β,γ-unsaturation in the fatty acid chains. Our results are in good agreement

  14. Characterization of antimicrobial resistance in Salmonella enterica food and animal isolates from Colombia: identification of a qnrB19-mediated quinolone resistance marker in two novel serovars

    DEFF Research Database (Denmark)

    Karczmarczyk, M.; Martins, M.; McCusker, M.

    2010-01-01

    Ninety-three Salmonella isolates recovered from commercial foods and exotic animals in Colombia were studied. The serotypes, resistance profiles and where applicable the quinolone resistance genes were determined. Salmonella Anatum (n=14), Uganda (19), Braenderup (10) and Newport (10) were the most...... hitherto unrecognized in various Salmonella serovars in Colombia. We also report unusual high-level quinolone resistance in the absence of any DNA gyrase mutations in serovars S. Carrau, Muenchen and Uganda....

  15. 金属离子对喹诺酮活性影响的研究进展%Research Progress of Metal Ions Influence The Activity of Quinolone

    Institute of Scientific and Technical Information of China (English)

    范卓文; 朱丽华; 杨爽爽; 闫丽莉; 孙建华

    2014-01-01

    喹诺酮类药物以抗菌活性强、抗菌谱广、疗效确切等优点被广泛应用于临床,一些研究结果表明金属离子对喹诺酮类药物的活性有一定的影响。本文概述了喹诺酮类药物的发展及作用机制,总结了金属离子对喹诺酮类的作用及喹诺酮类药物金属配合物的活性,最后展望了喹诺酮类药物今后的发展。%Quinolone are widely used clinically because of its antibacterial activity, widely spectrum antimicrobial, curative ef-fect, etc.Some studies show that the metal ions affect the activity of quinolone.This paper outlines the development and action mecha-nism of quinolone. Summarizes the role of metal ions on metal quinolone and the biological activity of quinolone complexes. Finally, prospects of the development of quinolone.

  16. Alarmingly High Segregation Frequencies of Quinolone Resistance Alleles within Human and Animal Microbiomes Are Not Explained by Direct Clinical Antibiotic Exposure.

    Science.gov (United States)

    Field, Wesley; Hershberg, Ruth

    2015-05-26

    Antibiotic resistance poses a major threat to human health. It is therefore important to characterize the frequency of resistance within natural bacterial environments. Many studies have focused on characterizing the frequencies with which horizontally acquired resistance genes segregate within natural bacterial populations. Yet, very little is currently understood regarding the frequency of segregation of resistance alleles occurring within the housekeeping targets of antibiotics. We surveyed a large number of metagenomic datasets extracted from a large variety of host-associated and non host-associated environments for such alleles conferring resistance to three groups of broad spectrum antibiotics: streptomycin, rifamycins, and quinolones. We find notable segregation frequencies of resistance alleles occurring within the target genes of each of the three antibiotics, with quinolone resistance alleles being the most frequent and rifamycin resistance alleles being the least frequent. Resistance allele frequencies varied greatly between different phyla and as a function of environment. The frequency of quinolone resistance alleles was especially high within host-associated environments, where it averaged an alarming ∼ 40%. Within host-associated environments, resistance to quinolones was most often conferred by a specific resistance allele. High frequencies of quinolone resistance alleles were also found within hosts that were not directly treated with antibiotics. Therefore, the high segregation frequency of quinolone resistance alleles occurring within the housekeeping targets of antibiotics in host-associated environments does not seem to be the sole result of clinical antibiotic usage.

  17. Endochin optimization: structure-activity and structure-property relationship studies of 3-substituted 2-methyl-4(1H)-quinolones with antimalarial activity.

    Science.gov (United States)

    Cross, R Matthew; Monastyrskyi, Andrii; Mutka, Tina S; Burrows, Jeremy N; Kyle, Dennis E; Manetsch, Roman

    2010-10-14

    Since the 1940s endochin and analogues thereof were known to be causal prophylactic and potent erythrocytic stage agents in avian models. Preliminary screening in a current in vitro assay identified several 4(1H)-quinolones with nanomolar EC(50) against erythrocytic stages of multidrug resistant W2 and TM90-C2B isolates of Plasmodium falciparum. Follow-up structure-activity relationship (SAR) studies on 4(1H)-quinolone analogues identified several key features for biological activity. Nevertheless, structure-property relationship (SPR) studies conducted in parallel revealed that 4(1H)-quinolone analogues are limited by poor solubilities and rapid microsomal degradations. To improve the overall efficacy, multiple 4(1H)-quinolone series with varying substituents on the benzenoid quinolone ring and/or the 3-position were synthesized and tested for in vitro antimalarial activity. Several structurally diverse 6-chloro-2-methyl-7-methoxy-4(1H)-quinolones with EC(50) in the low nanomolar range against the clinically relevant isolates W2 and TM90-C2B were identified with improved physicochemical properties while maintaining little to no cross-resistance with atovaquone.

  18. In vivo sequential selection of Escherichia coli with topoisomerase- and efflux-mediated misleading quinolone resistance phenotypes.

    Science.gov (United States)

    Smati, Mounira; Emond, Jean-Philippe; Arlet, Guillaume; Tankovic, Jacques

    2012-02-01

    Two mutants of Escherichia coli (V1 and V2) with acquired mechanisms of resistance to fluoroquinolones were isolated sequentially from blood cultures of a patient with cholangiocarcinoma treated repeatedly with ofloxacin; a third mutant (V3) was isolated under ciprofloxacin therapy. All mutants were related clonally. V1 was susceptible to quinolones but with diminished susceptibility to ofloxacin. V2 was hypersusceptible to nalidixic acid but had high-level resistance to ofloxacin. V3 was resistant to all quinolones. Ofloxacin selected for original gyrA and parC mutations, leading to the unusual and misleading resistance phenotypes of V1 and V2, whereas efflux played a major role in the increased resistance of V3.

  19. Switching electrical conductivity in an AOT-isooctane-water microemulsion through photodimerization of solubilized N-methyl-2-quinolone.

    Science.gov (United States)

    Bufe, Markus; Wolff, Thomas

    2006-09-28

    The electrical conductivity of microemulsions composed of Aerosol OT (AOT), isooctane and water as a function of temperature was studied in the absence and presence of N-methyl-2-quinolone (NMQ), and consequences of an in situ photodimerization of NMQ were investigated. A conductivity increase upon raising the temperature of a water-in-oil microemulsion indicates percolation. Percolation temperatures (Tp) can be influenced specifically by the addition of certain substances. Small amounts of solubilized N-methyl-2-quinolone induce lower Tp (by up to 9 K), and photodimerization of NMQ shifts Tp back to higher values. Consequently, the microemulsion can be switched from conducting to non-conducting without varying temperature or composition by exposing samples to UV light at lambda > 310 nm. The effect can be reverted in part by irradiation at lambda = 250 nm. Coumarin derivatives--structurally related to NMQ--show much slighter effects.

  20. Emergency planning and the acute toxic potency of inhaled ammonia.

    Science.gov (United States)

    Michaels, R A

    1999-08-01

    Ammonia is present in agriculture and commerce in many if not most communities. This report evaluates the toxic potency of ammonia, based on three types of data: anecdotal data, in some cases predating World War 1, reconstructions of contemporary industrial accidents, and animal bioassays. Standards and guidelines for human exposure have been driven largely by the anecdotal data, suggesting that ammonia at 5,000-10,000 parts per million, volume/volume (ppm-v), might be lethal within 5-10 min. However, contemporary accident reconstructions suggest that ammonia lethality requires higher concentrations. For example, 33,737 ppm-v was a 5-min zero-mortality value in a major ammonia release in 1973 in South Africa. Comparisons of secondary reports of ammonia lethality with original sources revealed discrepancies in contemporary sources, apparently resulting from failure to examine old documents or accurately translate foreign documents. The present investigation revealed that contemporary accident reconstructions yield ammonia lethality levels comparable to those in dozens of reports of animal bioassays, after adjustment of concentrations to human equivalent concentrations via U.S. Environmental Protection Agency (EPA) procedures. Ammonia levels potentially causing irreversible injury or impairing the ability of exposed people to escape from further exposure or from coincident perils similarly have been biased downwardly in contemporary sources. The EPA has identified ammonia as one of 366 extremely hazardous substances subject to community right-to-know provisions of the Superfund Act and emergency planning provisions of the Clean Air Act. The Clean Air Act defines emergency planning zones (EPZs) around industrial facilities exceeding a threshold quantity of ammonia on-site. This study suggests that EPZ areas around ammonia facilities can be reduced, thereby also reducing emergency planning costs, which will vary roughly with the EPZ radius squared.

  1. Quinolone-resistance in Salmonella is associated with decreased mRNA expression of virulence genes invA and avrA, growth and intracellular invasion and survival.

    Science.gov (United States)

    Wang, Yu-Ping; Li, Lin; Shen, Jian-Zhong; Yang, Fu-Jiang; Wu, Yong-Ning

    2009-02-01

    A variety of environmental factors, such as oxygen, pH, osmolarity and antimicrobial agents, modulate the expression of Salmonella pathogenicity islands (SPI) genes. This study investigated SPI-1 gene expression and the pathogenicity of quinolone-resistant Salmonella. mRNA expression levels of the invA and avrA genes, located in SPI-1, in quinolone-susceptible and quinolone-resistant Salmonella strains were determined using real-time fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR). Twenty-five quinolone-resistant Salmonella mutants were derived from quinolone-susceptible strains by multiple-passage selection through increasing concentrations of ciprofloxacin in vitro, while an additional 15 strains were quinolone-resistant Salmonella clinical isolates. Sequence analysis showed no gene deletion or point mutations of nine SPI-1 genes (including invA and avrA) occurred in either the selected or clinical quinolone-resistant strains, while a single gyrA point mutation (S83F) was observed in all 40 quinolone-resistant strains. The mRNA expression levels of invA and avrA were significantly decreased (P<0.005) in quinolone-resistant strains (clinically acquired or experimentally selected in vitro), compared to the quinolone-susceptible strains. The resistant strains also had a slower growth rate combined with decreased epithelial cell invasion and intracellular replication in epithelial cells and macrophages. The results suggest that quinolone-resistance may be associated with lower virulence and pathogenicity than in quinolone-susceptible strains.

  2. Pharmacokinetics of Sparfloxacin in the Serum and Vitreous Humor of Rabbits: Physicochemical Properties That Regulate Penetration of Quinolone Antimicrobials

    Science.gov (United States)

    Liu, Weiguo; Liu, Qing Feng; Perkins, Ruth; Drusano, George; Louie, Arnold; Madu, Assumpta; Mian, Umar; Mayers, Martin; Miller, Michael H.

    1998-01-01

    We have used a recently described animal model to characterize the ocular pharmacokinetics of sparfloxacin in vitreous humor of uninfected albino rabbits following systemic administration and direct intraocular injection. The relationships of lipophilicity, protein binding, and molecular weight to the penetration and elimination of sparfloxacin were compared to those of ciprofloxacin, fleroxacin, and ofloxacin. To determine whether elimination was active, elimination rates following direct injection with and without probenecid or heat-killed bacteria were compared. Sparfloxacin concentrations were measured in the serum and vitreous humor by a biological assay. Protein binding and lipophilicity were determined, respectively, by ultrafiltration and oil-water partitioning. Pharmacokinetic parameters were characterized with RSTRIP, an iterative, nonlinear, weighted, least-squares-regression program. The relationship between each independent variable and mean quinolone concentration or elimination rate in the vitreous humor was determined by multiple linear regression. The mean concentration of sparfloxacin in the vitreous humor was 59.4% ± 12.2% of that in serum. Penetration of sparfloxacin, ciprofloxacin, fleroxacin, and ofloxacin into, and elimination from, the vitreous humor correlated with lipophilicity (r2 > 0.999). The linear-regression equation describing this relationship was not improved by including the inverse of the square root of the molecular weight and/or the degree of protein binding. Elimination rates for each quinolone were decreased by the intraocular administration of probenecid. Heat-killed Staphylococcus epidermidis decreased the rate of elimination of fleroxacin. Penetration of sparfloxacin into the noninflamed vitreous humor was greater than that of any quinolone previously examined. There was an excellent correlation between lipophilicity and vitreous entry or elimination for sparfloxacin as well as ciprofloxacin, fleroxacin, and ofloxacin

  3. Luminescent determination of quinolones in milk samples by liquid chromatography/post-column derivatization with terbium oxide nanoparticles.

    Science.gov (United States)

    Yánez-Jácome, G S; Aguilar-Caballos, M P; Gómez-Hens, A

    2015-07-31

    The usefulness of terbium oxide nanoparticles (Tb4O7NPs) as post-column derivatizing reagent for the liquid chromatographic determination of residues of quinolone antibiotics in milk samples has been studied. Seven quinolones of veterinary use have been chosen as model analytes to develop this method. The derivatization step is based on the formation of luminescent chelates of quinolones with Tb4O7NPs, which are monitored at λex=340nm and λem=545nm. Another relevant feature of the method is that the use of a 10-cm column and a ternary mixture of methanol, acetonitrile and acetic acid as mobile phase in gradient elution mode allow the chromatographic separation of the quinolones in about 13min, whereas previously described chromatographic methods require about 20min. The dynamic ranges of the calibration graphs and limits of detection are, respectively: 65-900ngmL(-1) and 35ngmL(-1) for marbofloxacin, 7.2-900ngmL(-1) and 2.5ngmL(-1) for ciprofloxacin, 6-900ngmL(-1) and 2ngmL(-1) for danofloxacin, 50-900ngmL(-1) and 20ngmL(-1) for enrofloxacin, 35-900ngmL(-1) and 12ngmL(-1) for sarafloxacin, 5-900ngmL(-1) and 2ngmL(-1) for oxolinic acid, and 7-900ngmL(-1) and 2.5ngmL(-1) for flumequine. The precision, established at two concentration levels of each analyte and expressed as the percentage of the relative standard deviation is in the range of 1.9-8.1% using standards, and of 3.4-10.7% in the presence of milk samples. The method has been satisfactorily applied to the analysis of skimmed, semi-skimmed and whole milk samples, with recoveries ranging from 89.0 to 106.5%.

  4. 2'-substituted analogs of cocaine: synthesis and dopamine transporter binding potencies.

    Science.gov (United States)

    el-Moselhy, T F; Avor, K S; Basmadjian, G P

    2001-09-01

    A series of 2'-substituted cocaine analogs (4-8) was prepared and evaluated in an in vitro dopamine transporter (DAT) binding assay. Compounds 4-7 were prepared by esterifying the 3 beta-hydroxyl group of ecgonine methyl ester (3) using the appropriate acid chloride in the presence of Et3N and benzene. Compound 3 was obtained from cocaine (1) by hydrolysis using 1N HCl to afford ecgonine.HCl which was subjected to acid catalyzed esterification using methanol saturated with HCl gas. Compound 8 was obtained by hydrogenation of 7 using H2/Pd-C. The IC50 values were calculated from displacement experiment of the radioligand [3H]WIN-35,428 (2). 2'-Aminococaine (8) showed high binding affinity to the DAT (14- and 1.3-fold more active than cocaine and the radioligand 2, respectively). These results, along with previous results, emphasize the importance of a hydrogen-bond donor group at the 2'-position of cocaine to enhance binding affinity to the DAT.

  5. High Resolution Melting Analysis for Rapid Mutation Screening in Gyrase and Topoisomerase IV Genes in Quinolone-Resistant Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Soo Tein Ngoi

    2014-01-01

    Full Text Available The increased Salmonella resistance to quinolones and fluoroquinolones is a public health concern in the Southeast Asian region. The objective of this study is to develop a high resolution melt curve (HRM assay to rapidly screen for mutations in quinolone-resistant determining region (QRDR of gyrase and topoisomerase IV genes. DNA sequencing was performed on 62 Salmonella strains to identify mutations in the QRDR of gyrA, gyrB, parC, and parE genes. Mutations were detected in QRDR of gyrA (n=52; S83F, S83Y, S83I, D87G, D87Y, and D87N and parE (n=1; M438I. Salmonella strains with mutations within QRDR of gyrA are generally more resistant to nalidixic acid (MIC 16>256 μg/mL. Mutations were uncommon within the QRDR of gyrB, parC, and parE genes. In the HRM assay, mutants can be distinguished from the wild-type strains based on the transition of melt curves, which is more prominent when the profiles are displayed in difference plot. In conclusion, HRM analysis allows for rapid screening for mutations at the QRDRs of gyrase and topoisomerase IV genes in Salmonella. This assay markedly reduced the sequencing effort involved in mutational studies of quinolone-resistance genes.

  6. The incidence of kidney injury for patients treated with a high-potency versus moderate-potency statin regimen after an acute coronary syndrome.

    Science.gov (United States)

    Sarma, Amy; Cannon, Christopher P; de Lemos, James; Rouleau, Jean L; Lewis, Eldrin F; Guo, Jianping; Mega, Jessica L; Sabatine, Marc S; O'Donoghue, Michelle L

    2014-05-01

    Observational studies have raised concerns that high-potency statins increase the risk of acute kidney injury. We therefore examined the incidence of kidney injury across 2 randomized trials of statin therapy. PROVE IT-TIMI 22 enrolled 4162 subjects after an acute coronary syndrome (ACS) and randomized them to atorvastatin 80 mg/day versus pravastatin 40 mg/day. A-to-Z enrolled 4497 subjects after ACS and randomized them to a high-potency (simvastatin 40 mg/day × 1 months, then simvastatin 80 mg/day) versus a delayed moderate-potency statin strategy (placebo × 4 months, then simvastatin 20 mg/day). Serum creatinine was assessed centrally at serial time points. Adverse events (AEs) relating to kidney injury were identified through database review. Across both trials, mean serum creatinine was similar between treatment arms at baseline and throughout follow-up. In A-to-Z, the incidence of a 1.5-fold or ≥ 0.3 mg/dL rise in serum creatinine was 11.4% for subjects randomized to a high-potency statin regimen versus 12.4% for those on a delayed moderate-potency regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.76 to 1.10; P=0.33). In PROVE IT-TIMI 22, the incidence was 9.4% for subjects randomized to atorvastatin 80 mg/day and 10.6% for subjects randomized to pravastatin 40 mg/day (OR, 0.88; 95% CI, 0.71 to 1.09; P=0.25). Consistent results were observed for different kidney injury thresholds and in individuals with diabetes mellitus or with moderate renal dysfunction. The incidence of kidney injury-related adverse events (AEs) was not statistically different for patients on a high-potency versus moderate-potency statin regimen (OR, 1.06; 95% CI, 0.68 to 1.67; P=0.78). For patients enrolled in 2 large randomized trials of statin therapy after ACS, the use of a high-potency statin regimen did not increase the risk of kidney injury.

  7. Removal of quinolone antibiotics from wastewaters by sorption and biological degradation in laboratory-scale membrane bioreactors.

    Science.gov (United States)

    Dorival-García, N; Zafra-Gómez, A; Navalón, A; González, J; Vílchez, J L

    2013-01-01

    Laboratory-scale batch experiments were developed to investigate the main removal routes for 6 commonly found quinolones (ciprofloxacin, moxifloxacin, norfloxacin, ofloxacin, pipemidic acid, and piromidic acid), in wastewaters from a wastewater treatment plant, at μg L(-1) levels in an aerobic sludge system from a membrane bioreactor (MBR) pilot plant. It was demonstrated that sorption and biotransformation were the main removal routes for the target antibiotics over other possible pathways, as volatilization or hydrolysis, under the experimental conditions. Mass balances indicated that sorption on sludge played a dominant role in the elimination of antibiotics from waters. The sorption coefficient K(d) depended strongly on temperature and on the quinolone type and were higher at lower temperatures and for piperazinylic quinolones. K(d) values were between 516 and 3746 L kg(-1) in the temperature range of 9-38°C. Higher mixed liquor suspended solids (MLSS) increased quinolone removal efficiency mainly by sorption. Quinolone biodegradation constituted a secondary pathway, and could be described by first-order kinetics with degradation-rate constants ranging from 8.0 × 10(-4)h(-1) to 1.4 × 10(-2)h(-1) within the same temperature range and MLSS from 7000 to 15,000 mg L(-1). Biodegradation depended on the MLSS and temperature, but also on the initial chemical oxygen demand (COD). Higher biodegradation rates were observed at higher MLSS and temperature, as well as at low initial COD. Ciprofloxacin and moxifloxacin registered the highest biodegradation percentages (52.8% and 47.2%, respectively, at 38°C and 15,000 mg L(-1) MLSS), which is evidence that, despite the known persistence of this group of antibiotics and removal from waters mainly by sorption, it was possible to improve their removal by biodegradation, with an appropriate selection of conditions and control of process variables, as a preliminary step towards the elimination of these antibiotics from the

  8. Quinolone co-resistance in ESBL- or AmpC-producing Escherichia coli from an Indian urban aquatic environment and their public health implications.

    Science.gov (United States)

    Bajaj, Priyanka; Kanaujia, Pawan Kumar; Singh, Nambram Somendro; Sharma, Shalu; Kumar, Shakti; Virdi, Jugsharan Singh

    2016-01-01

    Quinolone and β-lactam antibiotics constitute major mainstay of treatment against infections caused by pathogenic Escherichia coli. Presence of E. coli strains expressing co-resistance to both these antibiotic classes in urban aquatic environments which are consistently being used for various anthropogenic activities represents a serious public health concern. From a heterogeneous collection of 61 E. coli strains isolated from the river Yamuna traversing through the National Capital Territory of Delhi (India), those harboring blaCTX-M-15 (n = 10) or blaCMY-42 (n = 2) were investigated for co-resistance to quinolones and the molecular mechanisms thereof. Resistance was primarily attributed to amino acid substitutions in the quinolone resistance-determining regions (QRDRs) of GyrA (S83L ± D87N) and ParC (S80I ± E84K). One of the E. coli strains, viz., IPE, also carried substitutions in GyrB and ParE at positions Ser492→Asn and Ser458→Ala, respectively. The phenotypically susceptible strains nevertheless carried plasmid-mediated quinolone resistance (PMQR) gene, viz., qnrS, which showed co-transfer to the recipient quinolone-sensitive E. coli J53 along with the genes encoding β-lactamases and led to increase in minimal inhibitory concentrations of quinolone antibiotics. To the best of our knowledge, this represents first report of molecular characterization of quinolone co-resistance in E. coli harboring genes for ESBLs or AmpC β-lactamases from a natural aquatic environment of India. The study warrants true appreciation of the potential of urban aquatic environments in the emergence and spread of multi-drug resistance and underscores the need to characterize resistance genetic elements vis-à-vis their public health implications, irrespective of apparent phenotypic resistance.

  9. Early biochemical recurrence, urinary continence and potency outcomes following robot-assisted radical prostatectomy

    DEFF Research Database (Denmark)

    Berg, Kasper Drimer; Thomsen, Frederik Birkebæk; Hvarness, Helle

    2014-01-01

    OBJECTIVE: The aim of this study was to describe recovery of urinary continence and potency and report oncological and functional outcomes using the survival, continence and potency (SCP) system for patients undergoing robot-assisted radical prostatectomy (RARP). MATERIAL AND METHODS: From 2009...... with preoperative ESI, 77.6% (67.9-86.1) and 34.4% (24.1-47.5) maintained ESI 12 months postoperatively after bilateral and unilateral nerve-sparing surgery (NS), respectively. NS (p .... Using the SCP system and defining potency as ESI, functional and oncological success 12 months after surgery was achieved in 69 out of 135 (51.1%) preoperative continent and potent patients who underwent unilateral or bilateral NS, and did not require adjuvant treatment; when defining potency as IIEF...

  10. In vitro screening of the endocrine disrupting potency of brominated flame retardants and their metabolites

    NARCIS (Netherlands)

    Hamers, T.H.M.; Kamstra, J.H.; Sonneveld, E.; Murk, A.J.; Zegers, B.N.; Boon, J.P.; Brouwer, A.

    2004-01-01

    DEVELOPMENTAL AND REPRODUCTIVE TOXICITY vitro screening the endocrine disrupting potency brominated flame retardants and their metabolites Timo Hamers Jorke Kamstra Edwin Sonneveld Albertinka Murk Bart Zegers Jan Boon Abraham Brouwer Institute for Environmental Studies IVM Amsterdam BioDetection Sys

  11. The role of the 4''-hydroxyl on motilin agonist potency in the 9-dihydroerythromycin series.

    Science.gov (United States)

    Liu, Yaoquan; Carreras, Christopher W; Claypool, Mark; Myles, David C; Shaw, Simon J

    2011-06-15

    The role of the erythromycin 4''-hydroxyl group has been explored on the motilin agonist potential in the 9-dihydroerythromycin series of motilides. The compounds show potencies 2- to 4-fold superior to the corresponding hydroxylated compounds. The relationship is maintained when the 9-hydroxyl is alkylated to generate the corresponding 4''-deoxy-9-O-acetamido-9-dihydroerythromycins. However, concomitant with this increase in potency is an increase in hERG inhibition.

  12. Examining the profile of high-potency cannabis and its association with severity of cannabis dependence.

    Science.gov (United States)

    Freeman, T P; Winstock, A R

    2015-11-01

    Cannabis use is decreasing in England and Wales, while demand for cannabis treatment in addiction services continues to rise. This could be partly due to an increased availability of high-potency cannabis. Adults residing in the UK were questioned about their drug use, including three types of cannabis (high potency: skunk; low potency: other grass, resin). Cannabis types were profiled and examined for possible associations between frequency of use and (i) cannabis dependence, (ii) cannabis-related concerns. Frequent use of high-potency cannabis predicted a greater severity of dependence [days of skunk use per month: b = 0.254, 95% confidence interval (CI) 0.161-0.357, p cannabis was not associated with dependence (days of other grass use per month: b = 0.020, 95% CI -0.029 to 0.070, p = 0.436; days of resin use per month: b = 0.025, 95% CI -0.019 to 0.067, p = 0.245). Frequency of cannabis use (all types) did not predict severity of cannabis-related concerns. High-potency cannabis was clearly distinct from low-potency varieties by its marked effects on memory and paranoia. It also produced the best high, was preferred, and most available. High-potency cannabis use is associated with an increased severity of dependence, especially in young people. Its profile is strongly defined by negative effects (memory, paranoia), but also positive characteristics (best high, preferred type), which may be important when considering clinical or public health interventions focusing on cannabis potency.

  13. Probing the links between in vitro potency, ADMET and physicochemical parameters.

    Science.gov (United States)

    Gleeson, M Paul; Hersey, Anne; Montanari, Dino; Overington, John

    2011-03-01

    A common underlying assumption in current drug discovery strategies is that compounds with higher in vitro potency at their target(s) have greater potential to translate into successful, low-dose therapeutics. This has led to the development of screening cascades with in vitro potency embedded as an early filter. However, this approach is beginning to be questioned, given the bias in physicochemical properties that it can introduce early in lead generation and optimization, which is due to the often diametrically opposed relationship between physicochemical parameters associated with high in vitro potency and those associated with desirable absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics. Here, we describe analyses that probe these issues further using the ChEMBL database, which includes more than 500,000 drug discovery and marketed oral drug compounds. Key findings include: first, that oral drugs seldom possess nanomolar potency (50 nM on average); second, that many oral drugs have considerable off-target activity; and third, that in vitro potency does not correlate strongly with the therapeutic dose. These findings suggest that the perceived benefit of high in vitro potency may be negated by poorer ADMET properties.

  14. The octave potencies convention: a mathematical model of dilution and succussion.

    Science.gov (United States)

    Anick, David J

    2007-07-01

    Several hypothesized explanations for homeopathy posit that remedies contain a concentration of discrete information-carrying units, such as water clusters, nano-bubbles, or silicates. For any such explanation to be sustainable, dilution must reduce and succussion must restore the concentration of these units. Succussion can be modeled by a logistic equation, which leads to mathematical relationships involving the maximum concentration, the average growth of information-carrying units rate per succussion stroke, the number of succussion strokes, and the dilution factor (x, c, or LM). When multiple species of information-carrying units are present, the fastest-growing species will eventually come to dominate, as the potency is increased. An analogy is explored between iterated cycles dilution and succussion, in making homeopathic remedies, and iterated cycles of reseeding and growth, in bacterial cultures. Drawing on this analogy, the active ingredients in low and medium potency remedies may be present at early dilutions but only gradually come to 'dominate', while high potencies may develop from the occurrence of low-probability but faster-growing 'mutations.' Conclusions from this model include: 'x' and 'c' potencies are best compared by the amount of dilution, not the amount of succussion; the minimum number of succussion strokes needed per cycle is proportional to the logarithm of the dilution factor; and a plausible interpretation of why potencies at approximately regular ratios are traditionally used (the octave potencies convention).

  15. Kinetic microplate bioassays for relative potency of antibiotics improved by partial Least Square (PLS) regression.

    Science.gov (United States)

    Francisco, Fabiane Lacerda; Saviano, Alessandro Morais; Almeida, Túlia de Souza Botelho; Lourenço, Felipe Rebello

    2016-05-01

    Microbiological assays are widely used to estimate the relative potencies of antibiotics in order to guarantee the efficacy, safety, and quality of drug products. Despite of the advantages of turbidimetric bioassays when compared to other methods, it has limitations concerning the linearity and range of the dose-response curve determination. Here, we proposed to use partial least squares (PLS) regression to solve these limitations and to improve the prediction of relative potencies of antibiotics. Kinetic-reading microplate turbidimetric bioassays for apramacyin and vancomycin were performed using Escherichia coli (ATCC 8739) and Bacillus subtilis (ATCC 6633), respectively. Microbial growths were measured as absorbance up to 180 and 300min for apramycin and vancomycin turbidimetric bioassays, respectively. Conventional dose-response curves (absorbances or area under the microbial growth curve vs. log of antibiotic concentration) showed significant regression, however there were significant deviation of linearity. Thus, they could not be used for relative potency estimations. PLS regression allowed us to construct a predictive model for estimating the relative potencies of apramycin and vancomycin without over-fitting and it improved the linear range of turbidimetric bioassay. In addition, PLS regression provided predictions of relative potencies equivalent to those obtained from agar diffusion official methods. Therefore, we conclude that PLS regression may be used to estimate the relative potencies of antibiotics with significant advantages when compared to conventional dose-response curve determination.

  16. GABA potency at GABAA receptors found in synaptic and extrasynaptic zones

    Directory of Open Access Journals (Sweden)

    Martin eMortensen

    2012-01-01

    Full Text Available The potency of GABA is vitally important for its primary role in activating GABAA receptors and acting as an inhibitory neurotransmitter. Although numerous laboratories have presented information, directly or indirectly, on GABA potency, it is often difficult to compare across such studies given the inevitable variations in the methods used, the cell types studied, whether native or recombinant receptors are examined, and their relevance to native synaptic and extrasynaptic GABAA receptors. In this review, we list the most relevant isoforms of synaptic and extrasynaptic GABAA receptors that are thought to assemble in surface membranes of neurons in the central nervous system. Using consistent methodology in one cell type, the potencies of the endogenous neurotransmitter GABA are compared across a spectrum of GABAA receptors. The highest potency for GABA is measured when activating extrasynaptic-type α6 subunit-containing receptors, whereas synaptic-type α2β3γ2 and α3β3γ2 receptors exhibited the lowest potency, and other GABAA receptor subtypes that are found both in synaptic and extrasynaptic compartments, showed intermediate sensitivities to GABA. The relatively simple potency relationship between GABA and its target receptors is important as it serves as one of the major determinants of GABAA receptor activation, with consequences for the development of inhibition, either by tonic or phasic mechanisms.

  17. Mathematical analysis of the pharmacokinetic-pharmacodynamic (PKPD) behaviour of monoclonal antibodies: predicting in vivo potency.

    Science.gov (United States)

    Aston, Philip J; Derks, Gianne; Raji, Adewale; Agoram, Balaji M; van der Graaf, Piet H

    2011-07-21

    We consider the relationship between the target affinity of a monoclonal antibody and its in vivo potency. The dynamics of the system is described mathematically by a target-mediated drug disposition model. As a measure of potency, we consider the minimum level of the free receptor following a single bolus injection of the ligand into the plasma compartment. From the differential equations, we derive two expressions for this minimum level in terms of the parameters of the problem, one of which is valid over the full range of values of the equilibrium dissociation constant K(D) and the other which is valid only for a large drug dose or for a small value of K(D). Both of these formulae show that the potency achieved by increasing the association constant k(on) can be very different from the potency achieved by decreasing the dissociation constant k(off). In particular, there is a saturation effect when decreasing k(off) where the increase in potency that can be achieved is limited, whereas there is no such effect when increasing k(on). Thus, for certain monoclonal antibodies, an increase in potency may be better achieved by increasing k(on) than by decreasing k(off).

  18. Application of Sigmoidal Transformation Functions in Optimization of Micellar Liquid Chromatographic Separation of Six Quinolone Antibiotics.

    Science.gov (United States)

    Hadjmohammadi, Mohammadreza; Salary, Mina

    2016-03-01

    A chemometrics approach has been used to optimize the separation of six quinolone compounds by micellar liquid chromatography (MLC). A Derringer's desirability function, a multicriteria decision-making (MCDM) method, was tested for evaluation of two different measures of chromatographic performance (resolution and analysis time). The effect of three experimental parameters on a chromatographic response function (CRF) expressed as a product of two sigmoidal desirability functions was investigated. The sigmoidal functions were used to transform the optimization criteria, resolution and analysis time into the desirability values. The factors studied were the concentration of sodium dodecyl sulfate, butanol content and pH of the mobile phase. The experiments were done according to the face-centered cube central composite design, and the calculated CRF values were fitted to a polynomial model to correlate the CRF values with the variables and their interactions. The developed regression model showed good descriptive and predictive ability (R(2) = 0.815, F = 6.919, SE = 0.038, [Formula: see text]) and used, by a grid search algorithm, to optimize the chromatographic conditions for the separation of the mixture. The efficiency of prediction of polynomial model was confirmed by performing the experiment under the optimal conditions.

  19. Study of fluorescence characteristics of the charge-transfer reaction of quinolone agents with bromanil

    Science.gov (United States)

    Li, Wen-Ying; Chen, Xiao-Fang; Xuan, Chun-Sheng

    2009-01-01

    A spectrofluorimetric method was discussed for the determination of three antibacterial quinolone derivatives, ofloxacin (OFL), norfloxacin (NOR) and ciprofloxacin (CIP) through charge-transfer complexation (CTC) with 2,3,5,6-tetrabromo-1,4-benzoquinone (bromanil, TBBQ). The method was based on the reaction of these drugs as n-electron donors with the π-acceptor TBBQ. TBBQ was found to react with these drugs to produce a kind of yellow complexes and the fluorescence intensities of the complexes were enhanced by 29-36 times more than those of the corresponding monomers. UV-vis, 1H NMR and XPS techniques were used to study the complexes formed. The various experimental parameters affecting the fluorescence intensity were studied and optimized. Under optimal reaction conditions, the rectilinear calibration graphs were obtained in the concentration range of 0.021-2.42 μg mL -1, 0.017-2.63 μg mL -1 and 0.019-2.14 μg mL -1 for OFL, NOR and CIP, respectively. The methods developed were applied successfully to the determination of the subject drugs in their pharmaceutical dosage forms with good precision and accuracy compared to official and reported methods as revealed by t- and F-tests.

  20. Molecular characterization of genes encoding the quinolone resistance determining regions of Malaysian Streptococcus pneumoniae strains

    Directory of Open Access Journals (Sweden)

    Kumari N

    2008-01-01

    Full Text Available Genes encoding the quinolones resistance determining regions (QRDRs in Streptococcus pneumoniae were detected by PCR and the sequence analysis was carried out to identify point mutations within these regions. The study was carried out to observe mutation patterns among S. pneumoniae strains in Malaysia. Antimicrobial susceptibility testing of 100 isolates was determined against various antibiotics, out of which 56 strains were categorised to have reduced susceptibility to ciprofloxacin (≥2 μg/mL. These strains were subjected to PCR amplification for presence of the gyrA, parC , gyrB and parE genes. Eight representative strains with various susceptibilities to fluoroquinolones were sequenced. Two out of the eight isolates that were sequenced were shown to have a point mutation in the gyrA gene at position Ser81. The detection of mutation at codon Ser81 of the gyrA gene suggested the potential of developing fluoroquinolone resistance among S. pneumoniae isolates in Malaysia. However, further experimental work is required to confirm the involvement of this mutation in the development of fluoroquinolone resistance in Malaysia.

  1. Antimicrobial susceptibility testing of newer quinolones against gram positive and gram negative clinical isolates.

    Science.gov (United States)

    Iffat, Wajiha; Shoaib, Muhammad Harris; Muhammad, Iyad Naeem; Rehana; Tasleem, Samiah; Gauhar, Shahnaz

    2010-07-01

    Antibiotic resistance development is an ongoing process associated with irrational antibiotic use. WHO recommends regular surveillance programs for monitoring of antibiotic resistance. The present study is a step in this direction. A total of 124 clinical isolates of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa were collected from different hospitals in Karachi. In vitro antimicrobial susceptibility studies were carried out by agar dilution method using newer quinolones that included Gatifloxacin and Levofloxacin. It was observed that 50% (n=30) isolates of Staphylococcus aureus were resistant to gatifloxacin. Gatifloxacin was more active against Pseudomonas aeruginosa (n=23) and showing complete susceptibility with MIC 1mg/L except for three very resistant strains that shown resistance at even higher concentrations. Escherichia coli (n=45) has shown 15.5% and Klebsiella pneumoniae (n=26) 34.61% resistance to gatifloxacin. Levofloxacin was more active against Staphylococcus aureus and Escherichia coli showing complete susceptibility at 0.5 mg /L concentration. Pseudomonas aeruginosa and Klebsiella pneumoniae were found to be resistant to Levofloxacin showing 36.36% and 23.08% resistance respectively. The study strongly recommends the adherence to the antibiotic policy and regular susceptibility testing to overcome the problem associated with antimicrobial resistance.

  2. Activated carbon adsorption of quinolone antibiotics in water: Performance, mechanism, and modeling.

    Science.gov (United States)

    Fu, Hao; Li, Xuebing; Wang, Jun; Lin, Pengfei; Chen, Chao; Zhang, Xiaojian; Suffet, I H Mel

    2017-06-01

    The extensive use of antibiotics has led to their presence in the aquatic environment, and introduces potential impacts on human and ecological health. The capability of powdered activated carbon (PAC) to remove six frequently used quinolone (QN) antibiotics during water treatment was evaluated to improve drinking water safety. The kinetics of QN adsorption by PAC was best described by a pseudo second-order equation, and the adsorption capacity was well described by the Freundlich isotherm equation. Isotherms measured at different pH showed that hydrophobic interaction, electrostatic interaction, and π-π dispersion force were the main mechanisms for adsorption of QNs by PAC. A pH-dependent isotherm model based on the Freundlich equation was developed to predict the adsorption capacity of QNs by PAC at different pH values. This model had excellent prediction capabilities under different laboratory scenarios. Small relative standard derivations (RSDs), i.e., 0.59%-0.92% for ciprofloxacin and 0.09%-3.89% for enrofloxacin, were observed for equilibrium concentrations above the 0.3mg/L level. The RSDs increased to 11.9% for ciprofloxacin and 32.1% for enrofloxacin at μg/L equilibrium levels, which is still acceptable. This model could be applied to predict the adsorption of other chemicals having different ionized forms. Copyright © 2016. Published by Elsevier B.V.

  3. Determination of quinolones in plasma samples by capillary electrophoresis using solid-phase extraction.

    Science.gov (United States)

    Hernández, M; Borrull, F; Calull, M

    2000-06-09

    The potential of capillary zone electrophoresis (CZE) and micellar electrokinetic capillary chromatography (MEKC) have been investigated for the separation and quantitative determination of 10 quinolone antibiotics. The influence of different conditions, such as the buffer and pH of the electrolyte, the surfactant and the ion-pairing agents added to the electrolyte and the organic modifier were studied. A buffer consisting of 40 mM sodium tetraborate at pH 8.1 containing 10% (v/v) methanol was found to be a highly efficient electrophoretic system for separating lomefloxacin, enoxacin, norfloxacin, pipemidic acid, ofloxacin, piromidic acid, flumequine, oxolinic acid, cinoxacin and nalidixic acid. A solid-phase extraction method to remove the sample matrix (pig plasma samples) was developed on a C(18) cartridge using a mixture of methanol-water (70:30, v/v). The method is specific and reproducible and mean recoveries were in the range 94.0+/-4.2% and 123.3+/-4.1% for pig plasma samples over the range used. A linear relationship between concentration and peak area for each compound in pig plasma samples was obtained in the concentration range 5-20 mg l(-1) and detection limits were between 1.1 and 2.4 mg l(-1).

  4. Phage-Antibiotic Synergy (PAS): beta-lactam and quinolone antibiotics stimulate virulent phage growth.

    Science.gov (United States)

    Comeau, André M; Tétart, Françoise; Trojet, Sabrina N; Prère, Marie-Françoise; Krisch, H M

    2007-08-29

    Although the multiplication of bacteriophages (phages) has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage PhiMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS). A related effect was observed in diverse host-phage systems, including the T4-like phages, with beta-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.

  5. Degradation of quinolone antibiotic, norfloxacin, in aqueous solution using gamma-ray irradiation.

    Science.gov (United States)

    Sayed, Murtaza; Khan, Javed Ali; Shah, Luqman Ali; Shah, Noor S; Khan, Hasan M; Rehman, Faiza; Khan, Abdur Rahman; Khan, Asad M

    2016-07-01

    This study reports the efficiency of gamma-ray irradiation to degrade quinolone antibiotic, norfloxacin, in aqueous solution. Laboratory batch experiments were conducted to determine the "pseudo-first" order degradation kinetics of norfloxacin in the concentration ranges of 3.4-16.1 mg L(-1) by gamma-ray irradiation. The dose constant was found to be dependent on the initial concentration of norfloxacin and gamma-ray irradiation dose rate (D r). The saturation of norfloxacin sample solutions with N2, air or N2O, and the presence of tert-butanol and 2-propanol showed that (•)OH played more crucial role in the degradation of norfloxacin. The second order rate constants of (•)OH, eaq (-), and (•)H with norfloxacin were calculated to be 8.81 × 10(9), 9.54 × 10(8), and 1.10 × 10(9) M(-1) s(-1), respectively. The effects of various additives including CO3 (2-), HCO3 (-), NO3 (-), NO2 (-), and thiourea and the pH of the medium on the degradation of norfloxacin were also investigated. Norfloxacin degradation was lower in surface water and wastewater than in ultrapure water. Several degradation byproducts of norfloxacin were identified from which the possible degradation pathway was proposed.

  6. Phage-Antibiotic Synergy (PAS: beta-lactam and quinolone antibiotics stimulate virulent phage growth.

    Directory of Open Access Journals (Sweden)

    André M Comeau

    Full Text Available Although the multiplication of bacteriophages (phages has a substantial impact on the biosphere, comparatively little is known about how the external environment affects phage production. Here we report that sub-lethal concentrations of certain antibiotics can substantially stimulate the host bacterial cell's production of some virulent phage. For example, a low dosage of cefotaxime, a cephalosporin, increased an uropathogenic Escherichia coli strain's production of the phage PhiMFP by more than 7-fold. We name this phenomenon Phage-Antibiotic Synergy (PAS. A related effect was observed in diverse host-phage systems, including the T4-like phages, with beta-lactam and quinolone antibiotics, as well as mitomycin C. A common characteristic of these antibiotics is that they inhibit bacterial cell division and trigger the SOS system. We therefore examined the PAS effect within the context of the bacterial SOS and filamentation responses. We found that the PAS effect appears SOS-independent and is primarily a consequence of cellular filamentation; it is mimicked by cells that constitutively filament. The fact that completely unrelated phages manifest this phenomenon suggests that it confers an important and general advantage to the phages.

  7. Association of mutation patterns in GyrA and ParC genes with quinolone resistance levels in lactic acid bacteria.

    Science.gov (United States)

    Li, Shaoying; Li, Zhen; Wei, Wan; Ma, Chunyan; Song, Xiaomin; Li, Shufen; He, Wenying; Tian, Jianjun; Huo, Xiaoyan

    2015-02-01

    The quinolone resistance of 19 lactic acid bacterial strains belonging to the genera Enterococcus and Lactobacillus isolated from the natural fermented koumiss and yoghurt were investigated. The objective of this study was to determine the quinolone resistance levels and to explore the association of the resistance with the mutation patterns in gyrA and parC genes, as is currently recommended by the Food and Agriculture Organization/World Health Organization Joint Expert Committee in Guidelines for Evaluation of Probiotics in Food for probiotic lactic acid bacteria drug resistance in 2001. The Oxford Cup method and double-tube dilution method were used to determine the quinolone resistance levels of the isolated strains. Generally, all of the 19 strains showed resistance towards norfloxacin and ciprofloxacin when the Oxford cup method was used, whereas the incidence was lower (to norfloxacin 89.5% and to ciprofloxacin 68.4%) when minimum inhibitory concentration breakpoints (CLSI M100-S23) were tested. Furthermore, gene sequencing was conducted on gyrA and parC of topoisomerase II of these isolated strains. The genetic basis for quinolone resistance may be closely related to mutations in gyrA genes as there were 10 mutation sites in amino-acid sequences encoded by gyrA genes in 10 quinolone resistance strains and 14 mutation sites in Enterococcus durans HZ28, whereas no typical mutations were detected in parC genes.

  8. MATHEMATICAL MODELING FOR BENZYLPENICILIN POTASSIUM AND STREPTOMYCIN SULPHATE POTENCY DETERMINATION OF ASCOMICIN

    Directory of Open Access Journals (Sweden)

    Viviana Ciuca

    2016-12-01

    Full Text Available Ascomicin is an antibacterial unguent for treatment of local infections of skin, eyes, outer ear, in cattle, sheep, pig, dog and cat. The product contains two active substances: benzylpenicillin potassium (Penicillin G potassium and streptomycin sulphate. The main characteristic of commercial product is benzylpenicillin potassium and streptomycin sulphate potency. The potency is estimated by comparing the inhibition of growth of sensitive micro-organisms produced by known concentrations of the antibiotic to be examined and a reference substance. The validation study aims to demonstrate the determination of the potency of benzylpenicillin potassium and streptomycin sulphate, it is an appropriate analytical method, reproducible and meets the quality requirements of Ascomicin product. The paper establishes the performance characteristics of the method considered and identify the factors that influence these characteristics. The diameters of inhibition zones, directly proportional to the logarithm of the concentration of the antibiotic used for the assay, measured and calculated using statistical methods (Combistats Soft. The assay is designed in such a way that the mathematical model on which the potency equation is based can be proved to be valid. A parallel-line model is chosen. The two log dose response lines of the preparation under examination and the standard preparation are parallel; they are rectilinear over the range of doses used in the calculation. These conditions are verified by validity tests for a given probability (P = 0.05. The test is not valid unless the confidence limits (P = 0.95 are not less than 50 per cent and not more than 200 per cent of the estimated potency. The estimated potency is not less than 95 per cent and not more than 105 per cent of the stated potency. The stated potency is not less than 19400 international units/g benzylpenicillin potassium and 13960 international units/g streptomycin sulphate. The validation

  9. Characterization of Plasmid-Mediated Quinolone Resistance Determinants in High-Level Quinolone-Resistant Enterobacteriaceae Isolates from the Community: First Report of qnrD Gene in Algeria.

    Science.gov (United States)

    Yanat, Betitera; Machuca, Jesús; Díaz-De-Alba, Paula; Mezhoud, Halima; Touati, Abdelaziz; Pascual, Álvaro; Rodríguez-Martínez, José-Manuel

    2017-01-01

    The objective was to assess the prevalence of plasmid-mediated quinolone resistance (PMQR)-producing isolates in a collection of quinolone-resistant Enterobacteriaceae of community origin isolated in Bejaia, Algeria. A total of 141 nalidixic acid-resistant Enterobacteriaceae community isolates were collected in Bejaia (Northern Algeria) and screened for PMQR genes using polymerase chain reaction (PCR). For PMQR-positive strains, antimicrobial susceptibility testing was performed by broth microdilution and disk diffusion. Mutations in the quinolone resistance-determining regions of the target genes, gyrA and parC, were detected with a PCR-based method and sequencing. Southern blotting, conjugation and transformation assays and molecular typing by pulsed-field gel electrophoresis (PFGE), and multilocus sequence typing were also performed. The prevalence of PMQR-producing Enterobacteriaceae isolates was 13.5% (19/141); 11 of these isolates produced Aac(6')-Ib-cr and 8 were qnr-positive (4 qnrB1-like, 2 qnrS1-like, and 2 qnrD1-like), including the association with aac(6')-Ib-cr gene in three cases. PMQR gene transfer by conjugation was successful in 6 of 19 isolates tested. PFGE revealed that most of the PMQR-positive Escherichia coli isolates were unrelated, except for two groups comprising two and four isolates, respectively, including the virulent multidrug-resistant clone E. coli ST131 that were clonally related. Our findings indicate that PMQR determinants are prevalent in Enterobacteriaceae isolates from the community studied. We describe the first report of the qnrD gene in Algeria.

  10. Prescription of high-potency corticosteroid agents and clotrimazole-betamethasone dipropionate by pediatricians.

    Science.gov (United States)

    Fleischer, A B; Feldman, S R

    1999-10-01

    Family physicians, internists, and pediatricians are more likely to prescribe combination topical antifungal-topical corticosteroid preparations than are dermatologists. One such preparation, clotrimazole-betamethasone dipropionate, can cause atrophy because it has a high-potency corticosteroid component. We analyzed data from the National Ambulatory Medical Care Survey for visits to pediatricians from 1990 to 1994 and isolated visits at which a topical corticosteroid agent or clotrimazole-betamethasone dipropionate was prescribed. Pediatricians rarely prescribed single-agent, high-potency topical corticosteroid agents in managing patients with skin disorders. High-potency corticosteroid agents accounted for 5.0% of topical corticosteroid prescriptions, whereas 56.3% were low-potency and 38.7% were medium-potency agents. Of the 696,285 mentions of clotrimazole-betamethasone dipropionate, 56.4% (389,920) were for children aged newborn to 4 years; diagnoses were erythematodesquamatous dermatoses, diaper rash, tinea, well-baby visit, and candidiasis. In contrast, for dermatologists nationwide, no drug mention existed for this combination agent for children aged newborn to 4 years over the 5-year study period. Our results show that clotrimazole-betamethasone dipropionate is prescribed inappropriately by pediatricians, especially in the treatment of young children. Pediatricians rarely use high-potency topical corticosteroid agents, but most of their use of clotrimazole-betamethasone dipropionate is in the youngest children, in whom such corticosteroid use is least appropriate. This prescription pattern suggests that some pediatricians may be unaware that clotrimazole-betamethasone dipropionate has a high-potency cortico steroid component.

  11. Incipient cytotoxicity: A time-independent measure of cytotoxic potency in vitro.

    Science.gov (United States)

    Gülden, Michael; Kähler, Daria; Seibert, Hasso

    2015-09-01

    Time is an important determinant of toxicity but largely ignored in in vitro toxicity assays where exposure times chosen are rather arbitrary. To investigate the impact of time on the cytotoxic potency of chemicals in vitro, the concentration dependent cytotoxic action of selected chemicals (surfactants, metals, oxidative stressors, a mitochondrial poison) was determined after various exposure times (1-72 h) in cultures of Balb/c 3T3 cells. Time affected the cytotoxic potency as well as the cytotoxic efficacy. The median cytotoxic concentrations, EC50, decreased and in most cases approached an "incipient" value, EC50,∞, within 72 h. Cytotoxicity due to mitochondrial insult occurred after a threshold time which was dependent on the medium glucose concentration. Within the chemicals studied the extent of potency change with time ranged from 3- to >1000-fold and the "time to incipient cytotoxicity", tic, from 4 to >72 h. Hence, also the relative cytotoxic potencies depend on exposure time. Ignoring this may lead to severe bias in toxicological hazard and risk assessment. Therefore it is recommended to determine the incipient cytotoxic potency of chemical compounds, represented by, e.g., the incipient median effect (EC50,∞), no effect (NEC∞) or lowest effect concentrations (LEC∞) instead of measures obtained after arbitrary exposure times. If this is not possible, the 72 h-potency measurements appear to be useful surrogates. These time-independent incipient potency values can be reasonably compared between substances, endpoints, cells and biological test systems and may serve to define points of departure for quantitative in vitro-in vivo extrapolations.

  12. Synthesis and biological activities of pyrazolo[3,4-g]quinoxaline derivatives.

    Science.gov (United States)

    Gavara, Laurent; Saugues, Emmanuelle; Alves, Georges; Debiton, Eric; Anizon, Fabrice; Moreau, Pascale

    2010-11-01

    The synthesis of new pyrazolo[3,4-g]quinoxaline derivatives, as well as their Pim kinases (Pim-1, Pim-2, Pim-3) inhibitory potencies and in vitro antiproliferative activities toward a human fibroblast primary culture and three human solid cancer cell lines (PA1, PC3 and DU145) are described. The results obtained in this preliminary structure-activity relationship study have pointed out that most of the compounds in this series exhibited interesting in vitro Pim-3 kinase inhibitory potencies. Moreover, some of the tested compounds have demonstrated favorable antiproliferative potencies.

  13. Intramolecular hydrogen bond between 4-oxo and 3-carboxylic groups in quinolones and their analogs. Crystal structures of 7-methyl- and 6-fluoro-1,4-dihydro-4-oxocinnoline-3-carboxylic acids

    Science.gov (United States)

    Główka, Marek L.; Martynowski, Dariusz; Olczak, Andrzej; Bojarska, Joanna; Szczesio, Małgorzata; Kozłowska, Krystyna

    2003-09-01

    Crystal structures of two cinnoline analogs of quinolones and statistics on quinolones molecular forms observed in the crystal state have been determined. It has been shown that common quinolones may be divided into two main types, depending on presence of proton acceptor, usually aliphatic amine group, capable of protonation under mild conditions. Quinolones lacking amine group or having one(s) bound to an aromatic system exist at physiological pH mainly in a free acid form, in which acidic hydrogen atom is locked into an intramolecular hydrogen bond. The phenomenon enhances permeability of quinolones through lipophilic cell membranes but decreases the concentration of carboxylate form capable of specific binding with bacterial DNA. Molecular (neutral) form was observed exclusively in the crystalline state for these quinolones. The dominant forms seem different for quinolones having amine substituents with unconjugated lone pair electrons at N atom. Even in the crystalline state, they may exist also in a zwitterionic form, which was found to dominate in secondary amines crystallised at neutral pH. Our limited data suggest that position and order of amine group may play important role in controlling quinolones absorption, transport and concentration and thus their biological profile.

  14. Intravenous nursing progress quinolones The research progress of nursing on quinolones with intravenous injection%喹诺酮类药物静脉应用护理进展

    Institute of Scientific and Technical Information of China (English)

    杨希芳; 王静; 胡玉美

    2011-01-01

    对喹诺酮类药物的用药现状、不良反应及护理、配伍禁忌等进行了综述,旨在提高护理员对该药的认识,以提高疗效,保证用药安全。%Status of quinolones, adverse reactions and nursing, incompatibility etc.were reviewed, In order to improve cognition of care workers for the drugs, to improve efficacy and ensure safety of drugs.

  15. Using second-order calibration method based on trilinear decomposition algorithms coupled with high performance liquid chromatography with diode array detector for determination of quinolones in honey samples.

    Science.gov (United States)

    Yu, Yong-Jie; Wu, Hai-Long; Shao, Sheng-Zhi; Kang, Chao; Zhao, Juan; Wang, Yu; Zhu, Shao-Hua; Yu, Ru-Qin

    2011-09-15

    A novel strategy that combines the second-order calibration method based on the trilinear decomposition algorithms with high performance liquid chromatography with diode array detector (HPLC-DAD) was developed to mathematically separate the overlapped peaks and to quantify quinolones in honey samples. The HPLC-DAD data were obtained within a short time in isocratic mode. The developed method could be applied to determine 12 quinolones at the same time even in the presence of uncalibrated interfering components in complex background. To access the performance of the proposed strategy for the determination of quinolones in honey samples, the figures of merit were employed. The limits of quantitation for all analytes were within the range 1.2-56.7 μg kg(-1). The work presented in this paper illustrated the suitability and interesting potential of combining second-order calibration method with second-order analytical instrument for multi-residue analysis in honey samples.

  16. Changes of the Quinolones Resistance to Gram-positive Cocci Isolated during the Past 8 Years in the First Bethune Hospital

    Science.gov (United States)

    Xu, Jiancheng; Chen, Qihui; Yao, Hanxin; Zhou, Qi

    This study was to investigate the quinolones resistance to gram-positive cocci isolated in the First Bethune Hospital during the past 8 years. Disk diffusion test was used to study the antimicrobial resistance. The data were analyzed by WHONET 5 software according to Clinical and Laboratory Standards Institute (CLSI). The rates of methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative Staphylococci (MRCNS) were 50.8%∼83.3% and 79.4%∼81.5%during the past 8 years, respectively. In recent 8 years, the quinolones resistance to gram-positive cocci had increased. Monitoring of the quinolones resistance to gram-positive cocci should be strengthened. The change of the antimicrobial resistance should be investigated in order to guide rational drug usage in the clinic and prevent bacterial strain of drug resistance from being transmitted.

  17. Kojic Acid Effect on the Inhibitory Potency of Tyrosinase

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    Forogh Azami

    2017-04-01

    Full Text Available In recent years, enzymatic activity of tyrosinase has been the focus of investigation due to its potential applications in medicine, agriculture and cosmetics. Tyrosinase, entitled polyphenol oxidase, is a key enzyme that catalyzes synthesis of melanin in plants, microorganisms and mammalian cells. Presence of some antioxidants can delay or inhibit the activity of this enzyme as well. In this survey, molecular docking calculation method using Autodock 4.0 software for prediction of binding energy of the protein with some antioxidant ligands was executed. The pose with the lowest energy of binding or inhibition constant was extracted at 298.15 K for kojic acid. Number of conformations in the cluster of rank was 13. The first and second boxes free energy and the inhibition constant were as follows: -5.60 kcalmol-1, 78.99 µM and -3.32 kcalmol-1, 3.66 µM, respectively. Since the first box presented a lower value of free energy, it was considered as the best mode of structure of kojic acid and the protein docking for further analysis. Thus, our present study could contribute to development and discernment of tyrosinase inhibitors in order to prevent hyper pigmentation.

  18. Experimental evidence in support of the biological effects and physical basis of homeopathic potencies

    Directory of Open Access Journals (Sweden)

    Nirmal Sukul

    2012-09-01

    Full Text Available Background: Homeopathic potencies 12 cH and above cross the Avogadro number and, for this, do not contain any original drug molecules. Two major problems involved in the scientific study of potencies are (1 understanding the physical basis of potencies and (2 demonstrating the biological effects of potencies. The present study aims to address these questions. Methods and Results: In course of our experimental studies spanned over more than 30 years we have demonstrated significant effects of homeopathic potencies on man, animals and plants. We have also showed that potencies could be differentiated through their electronic spectra, and this difference in spectra can be attributed to the electron transfer interaction. In a molecular complex, electron of one molecule absorbs a quantum of visible radiation and is excited, not to a higher energy level of this molecule, but to one of the vacant high energy levels of the neighboring molecules. This process is known as electron or charge transfer interaction. This has been demonstrated in Iodine Ó© in two different solvents of CCl4 and aqueous ethanol (Sukul N C, Environ Ecol 17,866-872, 1999. We have further demonstrated that the effect of a homeopathic potency can be transmitted from one part of a plant to another, and also from one plant to another through water. I am presenting here a few selected cases of our experimental studies. Potentized Nux vomica significantly reduced ethanol consumption in rats by 73.7%and ethanol-induced sleep time in albino mice by 44.4%. Causticum 30 C and Rhus tox 30 C produced anti-inflamatory and anti-nocicptive effect on adjuvant arthritis in albino rats. Potentized homeopathic drugs reduced microfilaraemia by 28 to 100% and filariasis in two villages of West Bengal endemic for Bancroftian filaiasis. Potentized Cina and Thuja ameliorated trichinellosis in mice reducing larval population in muscles by 84% and 68%, respectively. Potencies of Agaricus and Nux

  19. Possible interaction of quinolone antibiotics with peptide transporter 1 in oral absorption of peptide-mimetic drugs.

    Science.gov (United States)

    Arakawa, Hiroshi; Kamioka, Hiroki; Kanagawa, Masahiko; Hatano, Yasuko; Idota, Yoko; Yano, Kentaro; Morimoto, Kaori; Ogihara, Takuo

    2016-01-01

    The study investigated whether quinolone antibiotics inhibit the PEPT1-mediated uptake of its substrates. Among the quinolones examined, lomefloxacin, moxifloxacin (MFLX) and purlifloxacin significantly inhibited the uptake of PEPT1 substrate phenylalanine-Ψ(CN-S)-alanine (Phe-Ψ-Ala) in HeLa/PEPT1 cells to 31.6 ± 1.3%, 27.6 ± 2.9%, 36.8 ± 2.2% and 32.6 ± 1.4%, respectively. Further examination showed that MFLX was an uncompetitive inhibitor, with an IC50 value of 4.29 ± 1.29 mm. In addition, MFLX significantly decreased the cephalexin and valacyclovir uptake in HeLa/PEPT1 cells. In an in vivo study in rats, the maximum plasma concentration (C(max)) of orally administered Phe-Ψ-Ala was significantly decreased in the presence of MFLX (171 ± 1 ng/ml) compared with that in its absence (244 ± 9 ng/ml). The area under the concentration-time curve (AUC) of orally administered Phe-Ψ-Ala in the presence of MFLX (338 ± 50 ng/ml · h) tended to decrease compared with that in its absence (399 ± 75 ng/ml · h). The oral bioavailability of Phe-Ψ-Ala in the presence and absence of MFLX was 41.7 ± 6.2% and 49.2 ± 9.2%, respectively. The results indicate that administration of quinolone antibiotics concomitantly with PEPT1 substrate drugs may potentially result in drug-drug interaction.

  20. Determinants of quinolone resistance in Escherichia coli causing community-acquired urinary tract infection in Bejaia, Algeria.

    Science.gov (United States)

    Betitra, Yanat; Teresa, Vinuesa; Miguel, Viñas; Abdelaziz, Touati

    2014-06-01

    To investigate the mechanisms of quinolone resistance and the association with other resistance markers among Esherichia coli (E. coli) strains isolated from outpatient with urinary tract infection in north of Algeria. A total of 30 nalidixic acid-resistant E. coli isolates from outpatient with urinary tract infections from January 2010 to April 2011 in north of Algeria (Bejaia) were studied. Antimicrobial susceptibility was determined by disc diffusion assay, minimal inhibitory concentrations (MIC) of quinolone were determined by microdilution. Mutations in the Quinolone Resistance-Determining Region (QRDR) of gyrA and parC genes and screening for qnr (A, B and S) and bla genes were done by PCR and DNA sequencing. Most of the E. coli isolates (56.66%) were shown to carry mutations in gyrA and parC (gyrA: Ser83Leu + Asp87Asn and parC:Ser80Ile). While, 16.66% had only an alteration in gyrA: Ser83Leu. One isolate produced qnrB-like and two qnrS-like. Four isolates were CTX-M-15 producers associated with TEM-1 producing in one case. Co-expression of blaCTX-M-15 and qnrB was determined in one E. coli isolate. Our findings suggested the community emergence of gyrA and parC alterations and Qnr determinants that contributed to the development and spread of fluoroquinolone resistance in Algerian E. coli isolates. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  1. Different types of copper complexes with the quinolone antimicrobial drugs ofloxacin and norfloxacin: structure, DNA- and albumin-binding.

    Science.gov (United States)

    Živec, Petra; Perdih, Franc; Turel, Iztok; Giester, Gerald; Psomas, George

    2012-12-01

    Three novel copper(II) complexes with the second-generation quinolone antibacterial agents norfloxacin (nfH) and ofloxacin (ofloH) have been synthesized resulting in the complexes [Cu(nfH)(phen)Cl]Cl·5H(2)O (1·5H(2)O), [Cu(nfH)(2)]Cl(2)·6H(2)O (2·6H(2)O) and [Cu(II)(ofloH)(2)][(Cu(I)Cl(2))(2)] (3), respectively. The crystal structures of the complexes have been determined by X-ray crystallography revealing that the quinolones act as bidentate ligands coordinated to Cu(II) atom through the pyridone oxygen and a carboxylato oxygen. UV study of the interaction of the quinolones and the complexes with calf-thymus DNA (CT DNA) has shown that they can bind to CT DNA with [Cu(II)(ofloxacin)(2)][(Cu(I)Cl(2))(2)] exhibiting the highest binding constant to CT DNA. The cyclic voltammograms of the complexes in the presence of CT DNA solution have shown that the interaction of the complexes with CT DNA is mainly through electrostatic binding. DNA solution viscosity measurements have shown that the interaction of the compounds with CT DNA by classical intercalation may be ruled out. Competitive studies with ethidium bromide (EB) indicate that the complexes can partially displace the DNA-bound EB suggesting low to moderate competition with EB. Norfloxacin, ofloxacin and their copper complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Susceptibility to β-lactams and quinolones of Enterobacteriaceae isolated from urinary tract infections in outpatients

    Science.gov (United States)

    Marchisio, Martín; Porto, Ayelén; Joris, Romina; Rico, Marina; Baroni, María R.; Di Conza, José

    2015-01-01

    Abstract The antibiotic susceptibility profile was evaluated in 71 Enterobacteriaceae isolates obtained from outpatient urine cultures in July 2010 from two health institutions in Santa Fe, Argentina. The highest rates of antibiotic resistance were observed for ampicillin (AMP) (69%), trimethoprim/sulfamethoxazole (TMS) (33%), and ciprofloxacin (CIP) (25%). Meanwhile, 21% of the isolates were resistant to three or more tested antibiotics families. Thirty integron-containing bacteria (42.3%) were detected, and a strong association with TMS resistance was found. Third generation cephalosporin resistance was detected in only one Escherichia coli isolate, and it was characterized as a bla CMY-2 carrier. No plasmid-mediated quinolone resistance (PMQR) was found. Resistance to fluoroquinolone in the isolates was due to alterations in QRDR regions. Two mutations in GyrA (S83L, D87N) and one in ParC (S80I) were observed in all CIP-resistant E. coli. It was determined to be the main phylogenetic groups in E. coli isolates. Minimum Inhibitory Concentration (MIC) values against nalidixic acid (NAL), levofloxacin (LEV), and CIP were determined for 63 uropathogenic E. coli isolates as MIC50 of 4 μg/mL, 0.03125 μg/mL, and 0.03125 μg/mL, respectively, while the MIC90 values of the antibiotics were determined as 1024 μg/mL, 64 μg/mL, and 16 μg/mL, respectively. An association between the phylogenetic groups, A and B1 with fluoroquinolone resistance was observed. These results point to the importance of awareness of the potential risk associated with empirical treatment with both the families of antibiotics. PMID:26691475

  3. Susceptibility to β-lactams and quinolones of Enterobacteriaceae isolated from urinary tract infections in outpatients

    Directory of Open Access Journals (Sweden)

    Martín Marchisio

    2015-01-01

    Full Text Available AbstractThe antibiotic susceptibility profile was evaluated in 71 Enterobacteriaceae isolates obtained from outpatient urine cultures in July 2010 from two health institutions in Santa Fe, Argentina. The highest rates of antibiotic resistance were observed for ampicillin (AMP (69%, trimethoprim/sulfamethoxazole (TMS (33%, and ciprofloxacin (CIP (25%. Meanwhile, 21% of the isolates were resistant to three or more tested antibiotics families. Thirty integron-containing bacteria (42.3% were detected, and a strong association with TMS resistance was found. Third generation cephalosporin resistance was detected in only one Escherichia coli isolate, and it was characterized as a blaCMY-2 carrier. No plasmid-mediated quinolone resistance (PMQR was found. Resistance to fluoroquinolone in the isolates was due to alterations in QRDR regions. Two mutations in GyrA (S83L, D87N and one in ParC (S80I were observed in all CIP-resistant E. coli. It was determined to be the main phylogenetic groups in E. coli isolates. Minimum Inhibitory Concentration (MIC values against nalidixic acid (NAL, levofloxacin (LEV, and CIP were determined for 63 uropathogenic E. coli isolates as MIC50 of 4 μg/mL, 0.03125 μg/mL, and 0.03125 μg/mL, respectively, while the MIC90 values of the antibiotics were determined as 1024 μg/mL, 64 μg/mL, and 16 μg/mL, respectively. An association between the phylogenetic groups, A and B1 with fluoroquinolone resistance was observed. These results point to the importance of awareness of the potential risk associated with empirical treatment with both the families of antibiotics.

  4. Different Dynamic Patterns of β-Lactams, Quinolones, Glycopeptides and Macrolides on Mouse Gut Microbial Diversity.

    Science.gov (United States)

    Yin, Jia; M, Prabhakar; Wang, Shan; Liao, Shuo-Xi; Peng, Xin; He, Yan; Chen, Yi-Ran; Shen, Hua-Fang; Su, Jin; Chen, Ye; Jiang, Yun-Xia; Zhang, Guo-Xia; Zhou, Hong-Wei

    2015-01-01

    The adverse impact of antibiotics on the gut microbiota has attracted extensive interest, particularly due to the development of microbiome research techniques in recent years. However, a direct comparison of the dynamic effects of various types of antibiotics using the same animal model has not been available. In the present study, we selected six antibiotics from four categories with the broadest clinical usage, namely, β-lactams (Ceftriaxone Sodium, Cefoperazone/Sulbactam and meropenem), quinolones (ofloxacin), glycopeptides (vancomycin), and macrolides (azithromycin), to treat BALB/c mice. Stool samples were collected during and after the administration of antibiotics, and microbial diversity was analyzed through Illumina sequencing and bioinformatics analyses using QIIME. Both α and β diversity analyses showed that ceftriaxone sodium, cefoperazone/sulbactam, meropenem and vancomycin changed the gut microbiota dramatically by the second day of antibiotic administration whereas the influence of ofloxacin was trivial. Azithromycin clearly changed the gut microbiota but much less than vancomycin and the β-lactams. In general, the community changes induced by the three β-lactam antibiotics showed consistency in inhibiting Papillibacter, Prevotella and Alistipes while inducing massive growth of Clostridium. The low diversity and high Clostridium level might be an important cause of Clostridium difficile infection after usage of β-lactams. Vancomycin was unique in that it inhibited Firmicutes, mainly the genus Clostridium. On the other hand, it induced the growth of Escherichia and effect lasted for months afterward. Azithromycin and meropenem induced the growth of Enterococcus. These findings will be useful for understanding the potential adverse effects of antibiotics on the gut microbiome and ensuring their better usage.

  5. In vitro susceptibility pattern of acinetobacter species to commonly used cephalosporins, quinolones, and aminoglycosides

    Directory of Open Access Journals (Sweden)

    Prashanth K

    2004-01-01

    Full Text Available PURPOSE: Acinetobacter spp. is an emerging important nosocomial pathogen. Clinical isolates of this genus are often resistant to many antibiotics. The in vitro susceptibility of Acinetobacter isolates obtained from patients were tested for currently used antibiotics. In addition, the study aimed at biotyping of Acinetobacter baumannii. METHODS: A total of 66 isolates were phenotypically characterised through a large panel of 25 carbon assimilation tests and susceptibility through disc diffusion method with 10 antimicrobial agents were tested. MICs were determined only for second line broad-spectrum drugs such as cefotaxime, ceftazidime, amikacin, ciprofloxacin, and ofloxacin using NCCLS guidelines. RESULTS: Multiple drug resistance (MDR was only witnessed in A. baumannii and not in other Acinetobacter species. Aminoglycosides such as amikacin, netilmicin were most active against the MDR isolates tested (60% susceptibility. Ceftazidime was more active than cefotaxime. MDR A. baumannii strains were susceptible only to amikacin, netilmicin and ceftadizime. Ciprofloxacin had poor activity irrespective of isolates belonging to different DNA groups tested (58% resistance overall, 79% among A. baumannii. Strains of Biotypes 6 and 19 of A. baumannii showed broader resistance than those of biotype 10 and others. CONCLUSIONS: Strains of A. baumannii from patients in our hospital, were generally more resistant to quinolones, -lactam antibiotics, first and second generation cephalosporins and partially resistant to third generation cephalosporins and aminoglycosides. The strains belonging to other DNA groups of Acinetobacter were comparatively less resistant than A.baumannii, except ciprofloxacin. This study suggests that, a combination therapy, using a third generation cephalosporin and amikacin, would be best choice for treating Acinetobacter infections.

  6. Occurrence and fate of quinolone and fluoroquinolone antibiotics in a municipal sewage treatment plant.

    Science.gov (United States)

    Jia, Ai; Wan, Yi; Xiao, Yang; Hu, Jianying

    2012-02-01

    This study developed a method for analysis of nineteen quinolone and fluoroquinolone antibiotics (FQs) in sludge samples, and investigated the occurrence and fate of the FQs in a municipal sewage treatment plant (STP) with anaerobic, anoxic, and aerobic treatment processes. Eleven compounds, including pipemidic acid, fleroxacin, ofloxacin, norfloxacin, ciprofloxacin, enrofloxacin, lomefloxacin, sparfloxacin, gatifloxacin, moxifloxacin, and sarafloxacin (only in sludge), were detected in the STP. The predominance of ofloxacin and norfloxacin, followed by lomefloxacin, ciprofloxacin, gatifloxacin, and moxifloxacin, were found in wastewater, suspended solids, and sludge. The total concentrations of FQs were 2573 ± 241 ng/L, 1013 ± 218 ng/L, and 18.4 ± 0.9 mg/kg in raw sewage, secondary effluent, and sludge, respectively. Extremely low mass change percentages were observed for FQs in anaerobic, anoxic, and aerobic treatment units, suggesting biodegradation to be of minor importance in the removal of FQs in STPs. 50-87% of the initial FQs loadings (except for pipemidic acid (36%)) were ultimately found in the dewatered sludge. Mean removal efficiencies of FQs in the STP were 56-75%, except for new generation drugs such as moxifloxacin (40 ± 5%) and gatifloxacin (43 ± 13%). A significant positive correlation was found between removal efficiencies and K(d) of FQs. The major factor in the removal of FQs in the STP was sorption to sludge, which was not governed by hydrophobic interactions. The long-term cycling and persistence of FQs in the STP has made activated sludge as a huge reservoir of FQ antibiotics. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Plasmid-mediated quinolone resistance in typhoidal Salmonellae: A preliminary report from South India

    Directory of Open Access Journals (Sweden)

    V K Geetha

    2014-01-01

    Full Text Available Background: Fluoroquinolones are the drugs extensively employed for the treatment of Salmonella infections. Over the couple of decades that have elapsed since the introduction of fluoroquinolones, resistance to these agents by Enterobacteriaceae family members has become common and widespread. Although fluoroquinolone resistance is mediated by genomic DNA (deoxyribonucleic acid as well as plasmid DNA, the plasmid-mediated quinolone resistance (PMQR facilitates higher level resistance by interacting with genomic mechanism and is capable of horizontal spread. Materials and Methods: During a period of 1-year, 63 typhoidal Salmonellae were isolated from 14,050 blood cultures and one parietal wall abscess. 36 (56.25% were Salmonella Typhi and 27 (42% were Salmonella Paratyphi A. They were all screened for resistance by the disc diffusion method and their minimum inhibitory concentrations were determined using agar dilution, broth dilution and E-strip method. Ciprofloxacin resistant isolates were screened for PMQR determinants by polymerase chain reaction assay. Results: All the 63 isolates were resistant to nalidixic acid. Among the 36 S. Typhi isolates 20 were resistant to ciprofloxacin, of which 14 carried the plasmid gene qnrB and one carried the aac(6′-Ib-cr gene. qnrA and qnrS genes were not detected. Ciprofloxacin resistance was not seen in any of the S. Paratyphi A isolates. Conclusion: The antibiotic sensitivity pattern of typhoidal Salmonellae shows an increasing trend of PMQR. The allele B of qnr gene was found to be the predominant cause of PMQR in this study.

  8. Selection of appropriate analytical tools to determine the potency and bioactivity of antibiotics and antibiotic resistance$

    Institute of Scientific and Technical Information of China (English)

    Nishant A. Dafale n; Uttam P. Semwal; Rupak K. Rajput; G.N. Singh

    2016-01-01

    Antibiotics are the chemotherapeutic agents that kill or inhibit the pathogenic microorganisms. Re-sistance of microorganism to antibiotics is a growing problem around the world due to indiscriminate and irrational use of antibiotics. In order to overcome the resistance problem and to safely use antibiotics, the correct measurement of potency and bioactivity of antibiotics is essential. Microbiological assay and high performance liquid chromatography (HPLC) method are used to quantify the potency of antibiotics. HPLC method is commonly used for the quantification of potency of antibiotics, but unable to determine the bioactivity; whereas microbiological assay estimates both potency and bioactivity of antibiotics. Additionally, bioassay is used to estimate the effective dose against antibiotic resistant microbes. Simultaneously, microbiological assay addresses the several parameters such as minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC), mutation prevention concentration (MPC) and critical concentration (Ccr) which are used to describe the potency in a more informative way. Microbiological assay is a simple, sensitive, precise and cost effective method which gives reproducible results similar to HPLC. However, the HPLC cannot be a complete substitute for microbiological assay and both methods have their own significance to obtain more realistic and precise results.

  9. Patient Controlled Analgesia Used to Assess the Efficacy and Potency of a New Opioid

    Directory of Open Access Journals (Sweden)

    Brian Ginsberg

    1996-01-01

    Full Text Available Patient controlled analgesia (PCA is widely used for the management of postoperative pain. PCA also permits a comparison to be made among analgesics in the clinical setting because it limits the variability introduced by third parties. Use of PCA to establish efficacy and potency data for an investigational drug, pentamorphone, compared with morphine is reported. Pentamorphone was found to be more efficacious than morphine in the first hour after surgery because significantly more patients were able to achieve a visual analogue scale of less than 30 mm with pentamorphone. Thereafter pentamorphone and morphine were found to be equally efficacious. Initially pentamorphone may be more potent than morphine based on the greater volume of morphine used in the first hour of therapy. However, a potency ratio could not be determined because this result was under conditions of unequal analgesia. The potency ratio determined at 24 h of therapy under equianalgesic conditions (252:1 is similar to previously reported potency data from laboratory studies (200:1. This study supports the use of PCA as a model to investigate and compare new drugs to establish their efficacy and potency.

  10. Assessment of toxic potency of complex mixtures of PAHs from Lincoln Creek, Milwaukee, WI

    Energy Technology Data Exchange (ETDEWEB)

    Villeneuve, D.; Crunkilton, R.; DeVita, W. [Univ. of Wisconsin, Stevens Point, WI (United States)

    1995-12-31

    An assay of cytochrome P4501A catalytic activity in PLHC-1 fish hepatoma cells was used to evaluate the toxic potency of dialysates from triolein filled semipermeable polymeric membrane devices (SPMDS) exposed for variable durations and under various flow regimes to water from Lincoln Creek. Toxic potency was expressed as 2,3,7,8 tetrachlorodibenzo-p-dioxin equivalents (TCDD-EQ) calculated from bioassay results. Dose-dependent responses in measured ethoxyresorufin-o-deethylase (EROD) activity of PLHC-1 cells exposed to SPMD dialysates were shown. Toxic potency of dialysates, expressed as bioassay derived TCDD equivalents, increased with duration of SPMD exposure in Lincoln Creek from 2.0 pg/uL for a 2 day exposure to 19.5 pg/uL for a 30 day exposure. This corresponded to an increase in dialysate polycyclic aromatic hydrocarbon (PAH) concentration from 8.82 ug/g after a 2 day exposure to 24.14 ug/g after 30 days. Dialysates from SPMDs exposed to Lincoln Creek stormflow had higher toxic potencies and total PAH concentrations than those exposed to baseflow only, These results suggest that levels of PAH contamination, particularly those associated with stormflow, in Lincoln Creek have potential to accumulate in fish to levels significant enough to elicit a measurable biological response (cytochrome P4501 A induction) at a potency level approaching 0.08% that of TCDD.

  11. Team Potency and Its Impact on Performance via Self-efficacy and Adaptability

    Directory of Open Access Journals (Sweden)

    Rodrigo Bastos Monteiro

    2016-01-01

    Full Text Available In sales, working together as a team for achieving individual performance is a relevant element. In this paper, we suggest a theoretical framework that analyzes the impact of team potency on subjective performance, according to two mechanisms: self-efficacy and adaptability. The hypotheses suggest that (a team potency has a positive relationship with self-efficacy and adaptability; self-efficacy and adaptability impact performance (b directly and (c indirectly, through a mediating role; and (d interpersonal climate quality moderates these associations. We did a national survey with 290 salespeople organized in 101 teams from a water purification company. We used multilevel analyses and results suggested that sales team potency has a main effect on self-efficacy and adaptability. Second, results showed that self-efficacy and adaptability explain subjective performance. Third, self-efficacy and adaptability mediate the association between team potency and individual performance. Fourth, we did not find support for a moderating role of interpersonal climate quality on team potency. Final remarks and future research are discussed in the paper.

  12. Fate and antibacterial potency of anticoccidial drugs and their main abiotic degradation products

    Energy Technology Data Exchange (ETDEWEB)

    Hansen, Martin [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)], E-mail: mah@farma.ku.dk; Krogh, Kristine A. [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark); Brandt, Asbjorn [Section of Veterinary Medicines, Danish Medicines Agency, Axel Heides Gade 1, DK-2300 Copenhagen (Denmark); Christensen, Jan H. [Section of Soil and Environmental Chemistry, Department of Basic Sciences and Environment, Faculty of Life Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg (Denmark); Halling-Sorensen, Bent [Section of Toxicology and Environmental Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen (Denmark)

    2009-02-15

    The antibacterial potency of eight anticoccidial drugs was tested in a soil bacteria bioassay (pour plate method), EC{sub 50}-values between 2.4 and 19.6 {mu}M were obtained; however, one compound, nicarbazin exhibited an EC{sub 50}-value above the maximum tested concentration (21 {mu}M, 9.1 mg L{sup -1}). The potency of mixtures of two of the compounds, narasin and nicarbazin, was synergistic (more than additive) with 10-fold greater antibacterial potency of the mixture than can be explained by their individual EC{sub 50}-values. The influence of pH, temperature, oxygen concentration and light on the transformation of robenidine and salinomycin was investigated. Robenidine was transformed by photolysis (DT{sub 50} of 4.1 days) and was unstable at low pH (DT{sub 50} of approximately 4 days); salinomycin was merely transformed at low pH, the latter into an unknown number of products. The antibacterial potency of the mixtures of transformation products of robenidine after photolysis and at low pH was comparable with that of the parent compound. Finally five photo-transformation products of robenidine were structural elucidated by accurate mass measurements, i-FIT values (isotopic pattern fit) and MS/MS fragmentation patterns. - Five photo-transformation products of robenidine were structural elucidated. This mixture was found to have similar antibacterial potency as the parent compound.

  13. Development of an Innovative in Vitro Potency Assay for Anti-Botulinum Antitoxins

    Directory of Open Access Journals (Sweden)

    Osnat Rosen

    2016-09-01

    Full Text Available Botulinum neurotoxins are bacterial proteins that cause botulism, a life-threatening disease. Therapy relies mostly on post-intoxication antibody treatment. The only accepted method to measure the potency of, and to approve, antitoxin preparations is the mouse lethality neutralization bioassay. However, this assay is time-consuming, labor-intensive, costly, and raises ethical issues related to the large numbers of laboratory animals needed. Until now, all efforts to develop an alternative in vitro assay have not provided a valid replacement to the mouse potency assay. In the present study, we report the development of an innovative in vitro assay for determining botulinum antitoxin potency, using botulinum type B as a model. The concept of the assay is to mimic two fundamental steps in botulinum intoxication: receptor binding and catalytic activity. By simulating these steps in vitro we were able to accurately determine the potency of antitoxin preparations. The reproducibility of the assay was high with a CV < 13%. Most importantly, the antitoxin potency measured by the in vitro assay highly correlated with that measured by the standard in vivo mouse assay (r = 0.9842, p < 0.0001. Thus, this new in vitro assay has the potential to be considered, after validation, as a replacement to the mouse assay for quantitating neutralizing antibody concentrations in pharmaceutical botulinum antitoxin preparations. Future adoption of this in vitro assay would minimize the use of laboratory animals, speed up the time, and reduce the cost of botulinum antitoxin approval.

  14. 喹诺酮类药物临床应用及不良反应%Clinical application of quinolone antibiotics and analysis of adverse reactions

    Institute of Scientific and Technical Information of China (English)

    戴丽

    2012-01-01

    OBJECTIVE To analyze the structure feature of quinolone antibacterials, antibacterial spectrum and clinical application and adverse reactions. METHODS The clinical prescriptions on quinolone antibacterial statistics in 2010 were analyzed, including the drug using times, frequency and sorting, as well as the using purpose of quinolone drugs and the effects. RESULTS The quinolone drug using frequency = appearing times of a drug on prescriptions/total number of prescriptions. The top three antibiotics most frequently used were nofloxacin, ciprofloxacin and ofloxacin, which were widely used and accounted for 85. 3% of quinolone prescription drugs on prescriptions. CONCLUSION Quinolone drugs are important antibiotics which should be used reasonably and standardly to avoid adverse drug reactions.%目的 对喹诺酮类抗菌药物的结构特点、抗菌谱及临床应用范围、不良反应进行分析.方法 对医院2010年喹诺酮类抗菌药物临床处方进行统计,分析其药品临床使用处方数、频率和排序及喹诺酮类药物的用途及作用.结果 喹诺酮类药物使用频率=药品处方数/药品总处方数,其中使用频率最高的前3位为诺氟沙星、依诺沙星和氧氟沙星,占喹诺酮类抗菌药物处方总量的85.3%,在抗菌药物中运用广泛.结论 喹诺酮类在抗菌药物中占有重要地位,应规范、合理应用,防止造成药物不良反应.

  15. Isolation, molecular identification and quinolone-susceptibility testing of Arcobacter spp. isolated from fresh vegetables in Spain.

    Science.gov (United States)

    González, Ana; Bayas Morejón, Isidro Favián; Ferrús, María Antonia

    2017-08-01

    Some species of the Arcobacter genus are considered emerging foodborne and waterborne enteropathogens. However, the presence of Arcobacter spp. in vegetables very little is known, because most studies have focused on foods of animal origin. On the other hand, quinolones are considered as first-line drugs for the treatment of infection by campylobacteria in human patients, but few data are currently available about the resistance levels to these antibiotics among Arcobacter species. Therefore, the aim of this study was to investigate the presence and diversity of arcobacters isolated from fresh vegetables such as lettuces, spinaches, chards and cabbages. Resistance to quinolones of the isolates was also investigated. One hundred fresh vegetables samples purchased from seven local retail markets in Valencia (Spain) during eight months were analysed. The study included 41 lettuces, 21 spinaches, 34 chards and 4 cabbages. Samples were analysed by culture and by molecular methods before and after enrichment. By culture, 17 out of 100 analysed samples were Arcobacter positive and twenty-five isolates were obtained from them. Direct detection by PCR was low, with only 4% Arcobacter spp. positive samples. This percentage increased considerably, up 20%, after 48 h enrichment. By polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), 17 out of the 25 isolates were identified as A. butzleri and 8 as A. cryaerophilus. Only two A. butzleri isolates showed resistance to levofloxacin and ciprofloxacin. The sequencing of a fragment of the QRDR region of the gyrA gene from the quinolones-resistant isolates revealed the presence of a mutation in position 254 of this gene (C-T transition). This study is the first report about the presence of pathogenic species of Arcobacter spp. in chards and cabbages and confirms that fresh vegetables can act as transmission vehicle to humans. Moreover, the presence of A. butzleri quinolone resistant in vegetables could

  16. Impact of a short exposure to levofloxacin on faecal densities and relative abundance of total and quinolone-resistant Enterobacteriaceae.

    Science.gov (United States)

    Bernard, J; Armand-Lefèvre, L; Luce, E; El Mniai, A; Chau, F; Casalino, E; Andremont, A; Ruppé, E

    2016-07-01

    Emergence of resistant Enterobacteriaceae in the intestinal microbiota during antibiotic treatment is well documented but its early dynamic is not. Here, we compared the densities of total Enterobacteriaceae and relative abundance (RA) of quinolone-resistant Enterobacteriaceae (QRE) in the first stool passed by patients who had a short exposure to levofloxacin (levofloxacin, n=12) or not (control, n=8). Mean densities (SD) (log CFU/g stool) of total Enterobacteriaceae were lower in the levofloxacin group than in the control group-3.4 (1.6) versus 6.7 (1.7), respectively, p Enterobacteriaceae and the QRE-RA.

  17. Progress in Synthesis of 4-Hydroxyquinoline Derivatives%4-羟基喹啉类化合物的合成研究进展

    Institute of Scientific and Technical Information of China (English)

    茆勇军; 何海军

    2014-01-01

    4-羟基喹啉类[4-hydroxyquinolines或4(1H)quinolones]化合物是一类重要的药物合成中间体,在抗疟、抗癌、抗菌、抗病毒、抗糖尿病等领域发挥重要作用。本文综述了4-羟基喹啉类衍生物的合成方法,包括热环合、碱环合和还原环合等。%4-Hydroxyquinoline [or 4(1H)quinolone] derivatives are important intermediates in pharmaceutical synthesis and play significant roles in antimalarial, anticancer, antibacterial, antiviral and antidiabetic. Progress in synthesis of 4-hydroxyquinoline derivatives, including thermal, basic and reductive cyclization methods, are summarized.

  18. Simultaneous Quantification of Limonin, Two Indolequinazoline Alkaloids, and Four Quinolone Alkaloids in Evodia rutaecarpa (Juss.) Benth by HPLC-DAD Method

    OpenAIRE

    Pei-ting Zhang; Bi-yan Pan; Qiong-feng Liao; Mei-cun Yao; Xin-jun Xu; Jin-zhi Wan; Dan Liu; Zhi-yong Xie

    2013-01-01

    A simple and efficient HPLC-DAD (225 nm) method was developed and validated for the simultaneous determination of limonin and six key alkaloids (evodiamine, rutaecarpine, 1-methyl-2-undecyl-4(1H)-quinolone, evocarpine, 1-methy-2-[(6Z,9Z)]-6,9-pentadecadienyl-4-(1H)-quinolone, and dihydroevocarpine) in Evodia rutaecarpa (Juss.) Benth, which has been widely used as one of the Traditional Chinese Medicines. The chromatographic separation was carried out on a Hypersil BDS C18 column, and gradient...

  19. The effect of electrical lighting power and irradiance on indoor-grown cannabis potency and yield.

    Science.gov (United States)

    Potter, David J; Duncombe, Paul

    2012-05-01

    The floral development and potencies [Δ(9) -tetrahydrocannabinol (THC) contents] of cannabis plants were compared when grown indoors under high-pressure sodium lamps consuming electrical power at three densities (270, 400, and 600 W/m(2)). After a 3-week vegetative phase, plants were grown for 8 weeks, with lamps maintaining an artificial day length of 12 h. Foliar and floral yields were measured. Gas chromatography was used to measure the content of the psychoactive cannabinoid THC. Mean yields per unit of electrical power in each lighting regime ranged from 0.9 to 1.6 g/W, the highest being achieved in the lowest irradiance regime. The individual potencies of the separated leaf and flower materials were not affected by increasing irradiance. However, there was a corresponding increase in the overall potency of the aerial plant tissue. This was because of the plants in brighter conditions producing a higher proportion of floral material.

  20. The potency of cannabis in New Zealand from 1976 to 1996.

    Science.gov (United States)

    Poulsen, H A; Sutherland, G J

    2000-01-01

    The potency of cannabis plant and cannabis products seized in New Zealand over the period of 20 years is studied. The earlier part of the study includes mainly imported cannabis oil and cannabis resin, and both imported and locally grown cannabis plant, that was seized by the police. The later part of the study includes little imported material. Cannabis plant is now locally grown, cannabis oil is locally manufactured and imported cannabis resin is rarely seized. The average potency of the cannabis plant available to the user has not increased over the 20 years period. Cannabis leaf contains on average 1% THC and the female flowering heads on average 3.5% THC. The average potency of cannabis oil has dropped from its peak at 34% THC in 1985 to 13% THC in 1995.

  1. In vitro potency and combination testing of antimicrobial agents against Neisseria gonorrhoeae.

    Science.gov (United States)

    Bharat, Amrita; Martin, Irene; Zhanel, George G; Mulvey, Michael R

    2016-03-01

    Antimicrobial resistant Neisseria gonorrhoeae is a major concern to public health due to decreased susceptibility to frontline antimicrobials. To find agents that are active against N. gonorrhoeae, we tested antimicrobials alone or in combination by Etest gradient strips. The potencies (as assessed by minimum inhibitory concentrations) of twenty-five antimicrobials were evaluated against nine reference strains of N. gonorrhoeae (WHO F, G, K, L, M, N, O, P and ATCC 49226). Potency was greatest for netilmicin, quinupristin-dalfopristin, ceftriaxone, ertapenem and piperacillin-tazobactam. Combinations of azithromycin, moxifloxacin, or gentamicin with ceftriaxone, doripenem, or aztreonam were tested against reference isolates and the fractional inhibitory concentration index (FICI) was calculated. All nine combinations resulted in indifference (>0.5 FICI ≤ 4). Combinations with FICI gonorrhoeae. These data on antimicrobials with higher potency and combinations that did not show antagonism can help to guide larger scale susceptibility studies for antimicrobial resistant N. gonorrhoeae.

  2. Research strategies for design and development of NSAIDs: clue to balance potency and toxicity of acetanilide compounds.

    Science.gov (United States)

    Pal, A K; Sen, S; Ghosh, S; Bera, A K; Bhattacharya, S; Chakraborty, S; Banerjee, A

    2001-08-01

    Despite the fact that many modern drug therapies are based on the concept of enzyme inhibition, inhibition of several enzymes leads to pathological disorders. Clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) bind to the active site of the membrane protein, cyclooxygenase (COX) and inhibit the synthesis of prostaglandins, the mediators for causing inflammation. At the same time, inhibition of hepatic cysteine proteases by some NSAID metabolites like NAPQI is implicated in the pathogenesis of hepatotoxicity. As a part of our efforts to develop new effective NSAIDs, a comprehensive investigation starting from synthesis to the study of the final metabolism of acetanilide group of compound has been envisaged with appropriate feedback from kinetic studies to enhance our knowledge and technical competency to feed the know-how to the medicinal chemist to screen out and design new acetanilide derivatives of high potency and low toxicity. Structure-function relationship based on the interaction of acetanilide with its cognate enzyme, cyclooxygenase has been studied critically with adequate comparison with several other available crystal structures of COX-NSAID complexes. Furthermore, to make the receptor based drug design strategy a novel and comprehensive one, both the mechanism of metabolism of acetanilide and structural basis of inhibition of cysteine proteases by the reactive metabolite (NAPQI) formed by cytochrome P450 oxidation of acetanilide have been incorporated in the study. It is hoped that this synergistic approach and the results obtained from such consorted structural investigation at atomic level may guide to dictate synthetic modification with judicious balance between cyclooxygenase inhibition and hepatic cysteine protease inhibition to enhance the potential of such molecular medicine to relieve inflammation on one hand and low hepatic toxicity on the other.

  3. Observations of the effect of atmospheric processes on the genotoxic potency of airborne particulate matter

    DEFF Research Database (Denmark)

    Feilberg, Anders; Nielsen, Torben; Binderup, Mona-Lise

    2002-01-01

    In this study, the relationship between genotoxic potency and the occurrence of polycyclic aromatic hydrocarbons (PAH), including benzo(a)pyrene (BaP), and nitro-PAH in urban and semi-rural air masses has been investigated. The Salmonella/microsome assay has been used as a measure of genotoxic...... potency. We find that the ratios of BaP/ mutagenicity and PAH/mutagenicity are highly variable. The processes responsible for the variation are formation and degradation of mutagens and transport of polluted air masses from heavily industrialized regions, Air masses from Central Europe are shown...

  4. The spermicidal potency of Coca-Cola and Pepsi-Cola.

    Science.gov (United States)

    Hong, C Y; Shieh, C C; Wu, P; Chiang, B N

    1987-09-01

    The inhibitory effect of Old Coke, caffeine-free New Coke, New Coke, Diet Coke and Pepsi-Cola on human sperm motility was studied with a trans-membrane migration method. None of them could decrease sperm motility to less than 70% of control within one hour. A previous study which claimed a marked variation of spermicidal potencies among different formulations of Coca-Cola could not be confirmed. Even if cola has a spermicidal effect, its potency is relatively weak as compared with other well-known spermicidal agents.

  5. Evaluation of the potency activity of aphrodisiac in Eurycoma longifolia Jack.

    Science.gov (United States)

    Ang, H H; Ikeda, S; Gan, E K

    2001-08-01

    The butanol, methanol, water and chloroform extracts of the roots of Eurycoma longifolia Jack were studied using various tests of potency of treated male rats. The results showed that E. longifolia produced a dose-dependent, recurrent and significant increase in the episodes of penile reflexes as evidenced by increases in quick flips, long flips and erections of the treated male rats during the 30 min observation period. These results provide further evidence that E. longifolia increases the aphrodisiac potency activity in treated animals.

  6. Rationale for further medical and health research on high-potency sweeteners.

    Science.gov (United States)

    Schiffman, Susan S

    2012-10-01

    High-potency or artificial sweeteners have historically been considered inert compounds without physiological consequences other than taste sensations. However, recent data suggest that some of these sweeteners have biological effects that may impact human health. Furthermore, there are significant gaps in our current knowledge of the pharmacokinetics of these sweeteners, their potential for "sweetener-drug interactions" and their impact on appetite and body weight regulation. Nine research needs are described that address some of the major unknown issues associated with ingestion of high-potency sweeteners.

  7. Estrogenic potencies of resorcylic acid lactones and 17 beta-estradiol in female rats.

    Science.gov (United States)

    Everett, D J; Perry, C J; Scott, K A; Martin, B W; Terry, M K

    1987-01-01

    Uterotrophic response in sexually immature female rats has been used to rank the relative estrogenic potencies of six resorcylic acid lactones (RALs) and to compare their activities with that of 17 beta-estradiol. On oral administration, the estrogenic potency relative to 17 beta-estradiol is as follows: 7 alpha-zearalenol, 10 times less; zeranol, 150 times less; taleranol, 350 times less; zearalanone, 400 times less; zearalenone, 650 times less; 7 beta-zearalenol, 3500 times less. On subcutaneous administration, zeranol is 500 times less estrogenic than 17 beta-estradiol.

  8. Determination of quinolone residues in shrimp using liquid chromatography with fluorescence detection and residue confirmation by mass spectrometry.

    Science.gov (United States)

    Karbiwnyk, Christine M; Carr, Lori E; Turnipseed, Sherri B; Andersen, Wendy C; Miller, Keith E

    2007-07-23

    The quinolones, oxolinic acid (OXO), flumequine (FLU), and nalidixic acid (NAL), are antibacterial drugs effective against gram-negative bacteria. Quinolones are used in both human and veterinary medicine, but are currently not approved by the U.S. Food and Drug Administration for use in food fish. A liquid chromatography-fluorescence (LC-FL) method was developed to determine OXO, FLU, and NAL residues in shrimp. An additional liquid chromatography-mass spectrometry (LC-MS(n)) method was created to confirm these residues using the same sample extract. Samples were prepared with a simple ethyl acetate extraction followed by solvent exchange into 0.2% formic acid and cleaned-up with hexane. Reverse phase chromatography was used to separate the three compounds in both procedures. For the LC-FL determinative method, fluorescence emission was monitored at 369 nm with excitation at 327 nm. With electrospray ionization, the three most abundant ions from the MS3 product ion spectrum were used to identify OXO, FLU, and NAL in the confirmation procedure. Shrimp samples fortified at levels ranging from 7.5 to 100 ng g(-1) were used to validate both methods.

  9. Identification of the main quinolone resistance determinant in Campylobacter jejuni and Campylobacter coli by MAMA-DEG PCR.

    Science.gov (United States)

    Hormeño, Lorena; Palomo, Gonzalo; Ugarte-Ruiz, María; Porrero, M Concepción; Borge, Carmen; Vadillo, Santiago; Píriz, Segundo; Domínguez, Lucas; Campos, Maria J; Quesada, Alberto

    2016-03-01

    Among zoonotic diseases, campylobacteriosis stands out as the major bacterial infection producing human gastroenteritis. Antimicrobial therapy, only recommended in critical cases, is challenged by resistance mechanisms that should be unambiguously detected for achievement of effective treatments. Quinolone (ciprofloxacin) resistance of Campylobacter jejuni and Campylobacter coli, the 2 main Campylobacter detected in humans, is conferred by the mutation gyrA C-257-T, which can be genotyped by several methods that require a previous identification of the pathogen species to circumvent the sequence polymorphism of the gene. A multiplex PCR, based on degenerated oligonucleotides, has been designed for unambiguous identification of the quinolone resistance determinant in Campylobacter spp. isolates. The method was verified with 249 Campylobacter strains isolated from humans (141 isolates) and from the 3 most important animal sources for this zoonosis: poultry (34 isolates), swine (38 isolates), and cattle (36 isolates). High resistance to ciprofloxacin, MIC above 4μg/mL, linked to the mutated genotype predicted by MAMA-DEG PCR (mismatch amplification mutation assay PCR with degenerated primers) was found frequently among isolates from the different hosts.

  10. Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target.

    Directory of Open Access Journals (Sweden)

    Ivan Laponogov

    Full Text Available The 2.7 A crystal structure of the 55-kDa N-terminal breakage-reunion domain of topoisomerase (topo IV subunit A (ParC from Streptococcus pneumoniae, the first for the quinolone targets from a gram-positive bacterium, has been solved and reveals a 'closed' dimer similar in fold to Escherichia coli DNA gyrase subunit A (GyrA, but distinct from the 'open' gate structure of Escherichia coli ParC. Unlike GyrA whose DNA binding groove is largely positively charged, the DNA binding site of ParC exhibits a distinct pattern of alternating positively and negatively charged regions coincident with the predicted positions of the grooves and phosphate backbone of DNA. Based on the ParC structure, a new induced-fit model for sequence-specific recognition of the gate (G segment by ParC has been proposed. These features may account for the unique DNA recognition and quinolone targeting properties of pneumococcal type II topoisomerases compared to their gram-negative counterparts.

  11. A series of novel 1D coordination polymers constructed from metal?quinolone complex fragments linked by aromatic dicarboxylate ligands

    Science.gov (United States)

    He, Jiang-Hong; Xiao, Dong-Rong; Yan, Shi-Wei; Sun, Dian-Zhen; Chen, Hai-Yan; Wang, Xin; Yang, Juan; Ye, Zhong-Li; Yuan, Ruo; Wang, En-Bo

    2012-08-01

    Self-assembly of quinolones with metal salts in the presence of aromatic dicarboxylate ligands affords a series of novel 1D metal-quinolone complexes, namely [Mn(Hppa)(oba)]·3H2O (1), [Co(Hppa)(oba)]·3.25H2O (2), [Zn(Hppa)(sdba)]·1.5H2O (3), [Mn(Hcf)(bpda)(H2O)]·2H2O (4), [Mn(Hppa)2(bpdc)] (5) and [Mn(Hlome)2(bpdc)]·4H2O (6) (Hppa = Pipemidic acid, Hcf = ciprofloxacin, Hlome = lomefloxacin). The structures of compounds 1-3 consist of novel polymeric chains spanning two different directions, which display an intriguing 1D → 3D inclined polycatenation of supramolecular ladders. Compound 4 exhibits a chain compound formed from the interconnection of [Mn2(Hcf)2(μ-CO2)2] dimers with bpda ligands. Compounds 5 and 6 are similar chain compounds constructed from [Mn(Hppa)2] (or [Mn(Hlome)2]) fragments linked by bpdc ligands. The magnetic properties of 4 have been studied, which indicate the existence of antiferromagnetic interactions. Furthermore, the luminescent properties of compound 3 are discussed.

  12. Environment-sensitive quinolone demonstrating long-lived fluorescence and unusually slow excited-state intramolecular proton transfer kinetics

    Science.gov (United States)

    Zamotaiev, O. M.; Shvadchak, V.; Sych, T. P.; Melnychuk, N. A.; Yushchenko, D.; Mely, Y.; Pivovarenko, V. G.

    2016-09-01

    A new small fluorescent dye based on 3-hydroxybenzo[g]quinolone, a benzo-analogue of Pseudomonas quinolone signal species, has been synthesized. The dye demonstrates interesting optical properties, with absorption in the visible region, two band emission due to an excited-state intramolecular proton transfer (ESIPT) reaction and high fluorescence quantum yield in both protic and aprotic media. Time-resolved fluorescence spectroscopy shows that the ESIPT reaction time is unusually long (up to 8 ns), indicating that both forward and backward ESIPT reactions are very slow in comparison to other 3-hydroxyquinolones. In spite of these slow rate constants, the ESIPT reaction was found to show a reversible character as a result of the very long lifetimes of both N* and T* forms (up to 16 ns). The ESIPT reaction rate is mainly controlled by the hydrogen bond donor ability in protic solvents and the polarity in aprotic solvents. Using large unilamellar vesicles and giant unilamellar vesicles of different lipid compositions, the probe was shown to preferentially label liquid disordered phases.

  13. Enzyme-mediated quenching of the Pseudomonas quinolone signal (PQS promotes biofilm formation of Pseudomonas aeruginosa by increasing iron availability

    Directory of Open Access Journals (Sweden)

    Beatrix Tettmann

    2016-12-01

    Full Text Available The 2-alkyl-3-hydroxy-4(1H-quinolone 2,4-dioxygenase HodC was previously described to cleave the Pseudomonas quinolone signal, PQS, which is exclusively used in the complex quorum sensing (QS system of Pseudomonas aeruginosa, an opportunistic pathogen employing QS to regulate virulence and biofilm development. Degradation of PQS by exogenous addition of HodC to planktonic cells of P. aeruginosa attenuated production of virulence factors, and reduced virulence in planta. However, proteolytic cleavage reduced the efficacy of HodC. Here, we identified the secreted protease LasB of P. aeruginosa to be responsible for HodC degradation. In static biofilms of the P. aeruginosa PA14 lasB::Tn mutant, the catalytic activity of HodC led to an increase in viable biomass in newly formed but also in established biofilms, and reduced the expression of genes involved in iron metabolism and siderophore production, such as pvdS, pvdL, pvdA and pvdQ. This is likely due to an increase in the levels of bioavailable iron by degradation of PQS, which is able to sequester iron from the surrounding environment. Thus, HodC, despite its ability to quench the production of virulence factors, is contraindicated for combating P. aeruginosa biofilms.

  14. A rapid and sensitive resonance Rayleigh scattering spectra method for the determination of quinolones in human urine and pharmaceutical preparation.

    Science.gov (United States)

    Qiao, Man; Wang, Yaqiong; Liu, Shaopu; Liu, Zhongfang; Yang, Jidong; Zhu, Jinghui; Hu, Xiaoli

    2015-03-01

    A new method based on resonance Rayleigh scattering (RRS) was proposed for the determination of quinolones (QNS) at the nanogram level. In pH 3.3-4.4 Britton-Robinson buffer medium, quinolones such as ciprofloxacin, pipemidic acid (PIP), lomefloxacin (LOM), norfloxacin (NOR) and sarafloxacin (SAR) were protonated and reacted with methyl orange (MO) to form an ion-pair complex, which then further formed a six-membered ring chelate with Pd(II). As a result, new RRS spectra appeared and the RRS intensities were enhanced greatly. RRS spectral characteristics of the MO-QNS-Pd(II) systems, the optimum conditions for the reaction, and the influencing factors were investigated. Under optimum conditions, the scattering intensity (∆I) increments were directly proportional to the concentration of QNS with in certain ranges. The method had high sensitivity, and the detection limits (3σ) ranged from 6.8 to 12.6 ng/mL. The proposed method had been successfully applied for the determination of QNS in pharmaceutical formulations and human urine samples. In addition, the mechanism of the reaction system was discussed based on IR, absorption and fluorescence spectral studies. The reasons for the enhancement of scattering spectra were discussed in terms of fluorescence-scattering resonance energy transfer, hydrophobicity and molecular size.

  15. Study of the quenching effect of quinolones over CdTe-quantum dots using sequential injection analysis and multicommutation.

    Science.gov (United States)

    Molina-García, L; Llorent-Martínez, E J; Fernández-de Córdova, M L; Santos, J L M; Rodrigues, S S M; Ruiz-Medina, A

    2013-06-01

    The field of light-emitting nanoparticles has experienced an enormous development over the past two decades. The fluorescence of these nanometer-size crystalline particles, called quantum dots (QDs), can be both quenched and enhanced by different compounds. Since a high percentage of articles related to QDs are focused on theoretical studies, the development of analytical methods with real applications is an important step in order to progressively demonstrate the versatility of these particles. Moreover, taking into account that most of the QDs-based analytical methods are non-automated, the development of automated flow methodologies is still a field that presents an important analytical potential. With this purpose, two automatic methodologies, multicommutated flow injection analysis and sequential injection analysis, have been here applied to the analysis of quinolones in pharmaceutical formulations, making use of the quenching effect caused by the analytes over mercaptopropionic acid-capped CdTe QDs fluorescence. Both methodologies were compared in terms of versatility, sample throughput, sensitivity, etc., and applied to the determination of five quinolones in pharmaceutical preparations available in the Spanish Pharmacopoeia. The detection limits ranged between 26 and 50μmolL(-1), and Relative Standard Deviations lower than 3% were observed in all cases.

  16. QapR (PA5506) represses an operon that negatively affects the Pseudomonas quinolone signal in Pseudomonas aeruginosa.

    Science.gov (United States)

    Tipton, Kyle A; Coleman, James P; Pesci, Everett C

    2013-08-01

    Pseudomonas aeruginosa is a Gram-negative, opportunistic pathogen that can cause disease in varied sites within the human body and is a significant source of morbidity and mortality in those afflicted with cystic fibrosis. P. aeruginosa is able to coordinate group behaviors, such as virulence factor production, through the process of cell-to-cell signaling. There are three intercellular signaling systems employed by P. aeruginosa, and one of these systems utilizes the small molecule 2-heptyl-3-hydroxy-4-quinolone (Pseudomonas quinolone signal [PQS]). PQS is required for virulence in multiple infection models and has been found in the lungs of cystic fibrosis patients colonized by P. aeruginosa. In this study, we have identified an RpiR family transcriptional regulator, QapR, which is an autoregulatory repressor. We found that mutation of qapR caused overexpression of the qapR operon. We characterized the qapR operon to show that it contains genes qapR, PA5507, PA5508, and PA5509 and that QapR directly controls the transcription of these genes in a negative manner. We also show that derepression of this operon greatly reduces PQS concentration in P. aeruginosa. Our results suggest that qapR affects PQS concentration by repressing an enzymatic pathway that acts on PQS or a PQS precursor to lower the PQS concentration. We believe that this operon comprises a novel mechanism to regulate PQS concentration in P. aeruginosa.

  17. Molecular characterization of quinolone resistance mechanisms and extended-spectrum β-lactamase production in Escherichia coli isolated from dogs.

    Science.gov (United States)

    Meireles, D; Leite-Martins, L; Bessa, L J; Cunha, S; Fernandes, R; de Matos, A; Manaia, C M; Martins da Costa, P

    2015-08-01

    The increasing prevalence of antimicrobial resistances is now a worldwide problem. Investigating the mechanisms by which pets harboring resistant strains may receive and/or transfer resistance determinants is essential to better understanding how owners and pets can interact safely. Here, we characterized the genetic determinants conferring resistance to β-lactams and quinolones in 38 multidrug-resistant Escherichia coli isolated from fecal samples of dogs, through PCR and sequencing. The most frequent genotype included the β-lactamase groups TEM (n=5), and both TEM+CTX-M-1 (n=5). Within the CTX-M group, we identified the genes CTX-M-32, CTX-M-1, CTX-M-15, CTX-M-55/79, CTX-M-14 and CTX-M-2/44. Thirty isolates resistant to ciprofloxacin presented two mutations in the gyrA gene and one or two mutations in the parC gene. A mutation in gyrA (reported here for the first time), due to a transversion and transition (TCG→GTG) originating a substitution of a serine by a valine in position 83 was also detected. The plasmid-encoded quinolone resistance gene, qnrs1, was detected in three isolates. Dogs can be a reservoir of genetic determinants conferring antimicrobial resistance and thus may play an important role in the spread of antimicrobial resistance to humans and other co-habitant animals.

  18. Characterization of the quinolone resistant determining regions in clinical isolates of pneumococci collected in Canada

    Directory of Open Access Journals (Sweden)

    Melano Roberto

    2010-01-01

    Full Text Available Abstract Background The objective of this study was to examine Streptococcus pneumoniae isolates collected from a longitudinal surveillance program in order to determine their susceptibility to currently used fluoroquinolones and of the frequency and type of mutations in the quinolone-resistant determining regions (QRDRs of their parC and gyrA genes. Methods The Canadian Bacterial Surveillance Network has been collecting clinical isolates of S. pneumoniae from across Canada since 1988. Broth microdilution susceptibility testing was carried out according to the Clinical and Laboratory Standards Institute guidelines. The QRDRs of the parC and gyrA genes were sequenced for all isolates with ciprofloxacin MIC ≥ 4 mg/L, and a large representative sample of isolates (N = 4,243 with MIC ≤ 2 mg/L. Results A total of 4,798 out of 30,111 isolates collected from 1988, and 1993 to 2007 were studied. Of those isolates that were successfully sequenced, 184 out of 1,032 with mutations in parC only, 11 out of 30 with mutations in gyrA only, and 292 out of 298 with mutations in parC and gyrA were considered resistant to ciprofloxacin (MIC ≥ 4 mg/L. The most common substitutions in the parC were at positions 137 (n = 722, 79 (n = 209, and 83 (n = 56, of which substitutions at positions 79 and 83 were associated with 4-fold increase in MIC to ciprofloxacin, whereas substitutions at position 137 had minimal effect on the ciprofloxacin MIC. A total of 400 out of 622 isolates with Lys-137 parC mutation belonged to serotypes 1, 12, 31, 7A, 9V, 9N and 9L, whereas only 49 out of 3064 isolates with no mutations belonged to these serotypes. Twenty-one out of 30 isolates with substitutions at position 81 of the gyrA gene had an increased MIC to ciprofloxacin. Finally, we found that isolates with mutations in both parC and gyrA were significantly associated with increased MIC to fluoroquinolones. Conclusions Not all mutations, most frequently Lys-137, found in the

  19. In vitro activity of five quinolones and analysis of the quinolone resistance-determining regions of gyrA, gyrB, parC, and parE in Ureaplasma parvum and Ureaplasma urealyticum clinical isolates from perinatal patients in Japan.

    Science.gov (United States)

    Kawai, Yasuhiro; Nakura, Yukiko; Wakimoto, Tetsu; Nomiyama, Makoto; Tokuda, Tsugumichi; Takayanagi, Toshimitsu; Shiraishi, Jun; Wasada, Kenshi; Kitajima, Hiroyuki; Fujita, Tomio; Nakayama, Masahiro; Mitsuda, Nobuaki; Nakanishi, Isao; Takeuchi, Makoto; Yanagihara, Itaru

    2015-04-01

    Ureaplasma spp. cause several disorders, such as nongonococcal urethritis, miscarriage, and preterm delivery with lung infections in neonates, characterized by pathological chorioamnionitis in the placenta. Although reports on antibiotic resistance in Ureaplasma are on the rise, reports on quinolone-resistant Ureaplasma infections in Japan are limited. The purpose of this study was to determine susceptibilities to five quinolones of Ureaplasma urealyticum and Ureaplasma parvum isolated from perinatal samples in Japan and to characterize the quinolone resistance-determining regions in the gyrA, gyrB, parC, and parE genes. Out of 28 clinical Ureaplasma strains, we isolated 9 with high MICs of quinolones and found a single parC gene mutation, resulting in the change S83L. Among 158 samples, the ParC S83L mutation was found in 37 samples (23.4%), including 1 sample harboring a ParC S83L-GyrB P462S double mutant. Novel mutations of ureaplasmal ParC (S83W and S84P) were independently found in one of the samples. Homology modeling of the ParC S83W mutant suggested steric hindrance of the quinolone-binding pocket (QBP), and de novo prediction of peptide structures revealed that the ParC S84P may break/kink the formation of the α4 helix in the QBP. Further investigations are required to unravel the extent and mechanism of antibiotic resistance of Ureaplasma spp. in Japan.

  20. Analysis of 155 reports of ADR Induced by Quinolones%155例喹诺酮类药品不良反应分析

    Institute of Scientific and Technical Information of China (English)

    钟晗; 刘晓琰; 崔敏; 苏颖杰

    2013-01-01

    目的 研究喹诺酮类药物在临床治疗中发生的不良反应(ADR)情况,寻找应对该类药物ADR的临床策略.方法 采用回顾性研究方法,对我院2004~2011年上报的喹诺酮类药物ADR进行系统分析.结果 155例ADR报表中涉及9种喹诺酮类药物,左氧氟沙星ADR例次最多(105例次).主要不良反应表现为过敏反应(40.4%)和消化系统症状(27.1%).结论 对喹诺酮类药物的临床应用需加强监测,促进合理用药.%Objective To determine adverse drug reaction (ADR) occurrence associated with quinolones in clinical practices. Methods 155 reports of quinolones-induced ADR from 2010 to 2011 were analyzed. Results Nine drugs of quinolones were involved in 155 ADR reports, among which levofloxacin resulted in ADR most frequently(105 cases). The ADRs manifestations mainly covered allergies(40.4%) and digestive system disease symptoms(27.1%). Conclusion It is necessary to monitor clinical application of quinolones, therefore promote rational use of drug.

  1. 喹诺酮类药物的严重不良反应及合理应用%Serious ADRs of Quinolones and TheirRational Use

    Institute of Scientific and Technical Information of China (English)

    付铁梅; 田丽娟

    2011-01-01

    目的 促进喹诺酮类药物的合理使用,减少药品不良反应和耐药性的发生.方法 通过查阅文献等,对喹诺酮类药物的严重不良反应及产生原因进行分析,并提出合理使用的对策建议.结果 与结论随着喹诺酮类药物临床使用量不断增加,其严重药品不良反应的发生也越来越多.临床用药,一定要增强合理用药意识,确保患者用药安全有效.%Objective To promote the rational use of quinolones to reduce serious adverse drug reactions (ADRs) and occurrence of resistance to qmnolones. Methods The literature review was conducted to analyze the serious ADRs of quinolones and their causes, and the countermeasures of their rational use were proposed. Results and Conclusion As the clinical use of quinolones increasing, serious ADRs occur more and more, Both doctors and patients should enhance Erie awareness of rational use of quinolones to reduce the serious ADRs and ensure lhe safe and effective drug use m patients.

  2. 沙眼衣原体对喹诺酮类耐药机制的进展%Update on the mechanism of Chlamydia trachomatis resistance to quinolones

    Institute of Scientific and Technical Information of China (English)

    杨晓静; 刘全忠

    2009-01-01

    Quinolones are commonly used to treat Chlamydiatra chomatis inection in clinic at present.However,the resistance of Chlamydia trachomatis to quinolones has been increasingly reported.It has becn shown that the resistance is related to point mutations in the quinolone-resistance-determinning region of DNA gyrase gene and topoisomerase IV subunit genes.These mutations are located most commonly at Ser-83,less frequently at Asp-87.There are also some other mechanisms underlying the resistance.Further studies are needed for the elucidation of exact mechanism of Chlamydia trachomatis resistance to quinolones.%喹诺酮类药物目前在临床上常用于治疗沙眼衣原体感染,但近年来有关沙眼衣原体对其耐药的报道不断出现.研究发现,喹诺酮类耐药的产生与DNA回旋酶和拓扑异构酶Ⅳ亚单位基因的喹诺酮耐药决定区域的点突变有关.最常见的突变位于Ser-83,少数情况下位于Asp-87,还有一些其他可能的耐药机制.沙眼衣原体对喹诺酮类耐药的确切机制尚待进一步研究.

  3. Research progress on the metal complexes of quinolone drug ligands%喹诺酮类药物金属配合物的研究进展

    Institute of Scientific and Technical Information of China (English)

    康新平; 安哲

    2012-01-01

    Objective The article reviewed the development of the quinolone drug and the structure and potential activity of the quinolone drug metal complexes, in order to provide a foundation for further research. Methods The ralated literatures were summarized. Results The development of the research of the quinolone drug metal complexes is fast,but exists many questions. Conclusion Some suggestions of the in-depth research of the quinolone drug metal complexes are presented.%目的 对喹诺酮类药物的发展过程及其金属配合物的配位结构和活性等方面进行综述,为进一步研究喹诺酮类药物金属配合物提供科学依据.方法 对相关文献进行归纳、总结和综述.结果 喹诺酮类药物金属配合物的研究取得较快发展,但还存在着许多有待解决的问题.结论 展望了喹诺酮类药物金属配合物研究的发展趋势.

  4. [Simultaneous determination of 11 quinolones in hotpot ingredients by dispersive solid-phase extraction and ultra performance liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Cao, Peng; Mou, Yan; Gao, Fei; Geng, Jinpei; Zhang, Xiqing; Sui, Tao; Liang, Junni; Sha, Meilan; Guan, Lili

    2013-09-01

    A method for the simultaneous determination of the residues of 11 quinolones in hotpot ingredients by quick, easy, cheap, effective, rugged and safe (QuEChERS) extraction and ultra performance liquid chromatography-tandem mass spectrometric method (UPLC-MS/MS) was established. The sample was extracted with acetonitrile (containing 5% formic acid) and followed by stratifying with a salting-out agent. Clean-up of the extracts was processed by C18 and PSA, a modified QuEChERS procedure. The analytes were then separated on a Poroshell 120 EC-C18 column, and finally detected by tandem mass spectrometry in positive ESI mode. The linearity of all the 11 quinolones in the range from 1.0 to 100.0 microg/kg had correlation coefficients greater than 0.998. The limits of detection (LOD) of the method were from 1.8 to 3.1 microg/kg and the limits of quantification (LOQ) were from 6.0 to 10.3 microg/kg. The average recoveries of the 11 quinolones were in the range from 70.1% to 100.3%, with relative standard deviations from 2.42% to 10.88%. The established method is sensitive and of good recoveries. It can be applied as a rapid and reliable method for the determination of the 11 quinolones in hotpot ingredients.

  5. 4-(1H)-Quinolones and 1,2,3,4-Tetrahydroacridin-9(10H)-ones prevent the transmission of Plasmodium falciparum to Anopheles freeborni.

    Science.gov (United States)

    Sáenz, Fabián E; Lacrue, Alexis N; Cross, R Matthew; Maignan, Jordany R; Udenze, Kenneth O; Manetsch, Roman; Kyle, Dennis E

    2013-12-01

    Malaria kills approximately 1 million people a year, mainly in sub-Saharan Africa. Essential steps in the life cycle of the parasite are the development of gametocytes, as well as the formation of oocysts and sporozoites, in the Anopheles mosquito vector. Preventing transmission of malaria through the mosquito is necessary for the control of the disease; nevertheless, the vast majority of drugs in use act primarily against the blood stages. The study described herein focuses on the assessment of the transmission-blocking activities of potent antierythrocytic stage agents derived from the 4(1H)-quinolone scaffold. In particular, three 3-alkyl- or 3-phenyl-4(1H)-quinolones (P4Qs), one 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), and one 1,2,3,4-tetrahydroacridin-9(10H)-one (THA) were assessed for their transmission-blocking activity against the mosquito stages of the human malaria parasite (Plasmodium falciparum) and the rodent parasite (P. berghei). Results showed that all of the experimental compounds reduced or prevented the exflagellation of male gametocytes and, more importantly, prevented parasite transmission to the mosquito vector. Additionally, treatment with ICI 56,780 reduced the number of sporozoites that reached the Anopheles salivary glands. These findings suggest that 4(1H)-quinolones, which have activity against the blood stages, can also prevent the transmission of Plasmodium to the mosquito and, hence, are potentially important drug candidates to eradicate malaria.

  6. Clinical application of a ligation-independent pathway of multiplex ligation-dependent probe amplification for the determination of quinolone susceptibility of Streptococcus pneumoniae.

    Science.gov (United States)

    Uno, Naoki; Araki, Nobuko; Kaku, Norihito; Kosai, Kosuke; Hasegawa, Hiroo; Yanagihara, Katsunori

    2016-09-01

    We previously uncovered a ligation-independent pathway of multiplex ligation-dependent probe amplification (MLPA) through which products of MLPA could be amplified without both hybridization and ligation reactions. Here, we utilized this pathway to detect an antibiotic resistance mutation of quinolones in Streptococcus pneumoniae.

  7. Relative developmental toxicity potencies of retinoids in the embryonic stem cell test compared with their relative potencies in in vivo and two other in vitro assays for developmental toxicity

    NARCIS (Netherlands)

    Louisse, J.; Gönen, S.; Rietjens, I.M.C.M.; Verwei, M.

    2011-01-01

    The present study determines the relative developmental toxicity potencies of retinoids in the embryonic stem (ES)-D3 cell differentiation assay of the embryonic stem cell test, and compares the outcomes with their relative potencies in in vivo and two other in vitro assays for developmental toxicit

  8. Dose doubling, relative potency, and dose equivalence of potassium-sparing diuretics affecting blood pressure and serum potassium: systematic review and meta-analyses.

    Science.gov (United States)

    Roush, George C; Ernst, Michael E; Kostis, John B; Yeasmin, Shamima; Sica, Domenic A

    2016-01-01

    Potassium-sparing diuretics (PSDs) are valuable antihypertensives with additional benefits unrelated to control of systolic blood pressure (SBP). However, their key parameters affecting SBP and serum potassium are poorly defined, fostering underutilization. Consequently, we conducted systematic reviews and meta-analyses, yielding 3668 articles and ultimately 84 randomized comparisons. For office SBP, overall placebo-adjusted changes were triamterene -1.9 (low dose only), amiloride -9.9, spironolactone -13.2, and eplerenone -9.2. Differences in antihypertensive effect were due to potency rather than efficacy. Doubling amiloride, eplerenone, and spironolactone doses reduced SBP (95% confidence limits) on average by -2.3 (-3.1, -1.5). Relative antihypertensive potencies were spironolactone>amiloride>eplerenone. Spironolactone had significantly greater antihypertensive potency than amiloride, -4.0 (-7.4, -0.6), and eplerenone, -5.5 (-7.4, -3.6). Dose equivalencies were eplerenone-spironolactone 4.5-to-1 (e.g., eplerenone 125∼spironolactone 25), amiloride-spironolactone 3.3-to-1, and eplerenone-amiloride 1.4-to-1. Increases in serum potassium from amiloride and spironolactone at commonly used doses averaged 0.14-0.29 mEq/l; the dose doubling effect was 0.16 (0.10, 0.22). Spironolactone caused greater hyperkalemia than amiloride across their dose ranges: 0.14, P = 0.043. Seven features make important bias unlikely: a comprehensive literature search, adjustment for covariates, all models explaining 95-100% of the between-study variability, similar dose doubling effects among PSDs, two different methods giving the same potency sequence, similar results from double blind comparisons, and similar results for eplerenone versus spironolactone from analysing direct comparison data (i.e., no meta-regression) for office and 24-h SBP. This synthesis accomplishes for PSDs what has already been achieved for thiazide-type diuretics and other antihypertensives and can guide

  9. Microwave assisted synthesis of 2-pyridone and 2-pyridone based compounds

    Directory of Open Access Journals (Sweden)

    Mijin Dušan Ž.

    2014-01-01

    Full Text Available 2-Pyridones are important heterocyclic compounds that are widely used in medical chemistry, and their various derivatives have significant biological and medical applications. In this paper, the synthesis of 2-pyridones as well as 2-pyridone based compounds such as 2-quinolones using microwave assisted organic chemistry is reviewed. The review is divided in three parts. In the first part, microwave synthesis of 2-pyridones according to the type of condensation is discussed. In the second part, microwave assisted synthesis of 2-quionolones is listed. At the end of the review several examples of microwave synthesis of other 2-pyridone based compounds (ring fused N-substituted 2-pyridones are given. [Projekat Ministarstva nauke Republike Srbije, br. 172013

  10. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    NARCIS (Netherlands)

    Gibbs, S.; Corsini, E.; Spiekstra, S.W.; Galbiati, V.; Fuchs, H.W.; Degeorge, G.; Troese, M.; Hayden, P.; Deng, W.; Roggen, E.

    2013-01-01

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low

  11. Opportunities and strategies to further reduce animal use for Leptospira vaccine potency testing.

    Science.gov (United States)

    Walker, A; Srinivas, G B

    2013-09-01

    Hamsters are routinely infected with virulent Leptospira for two purposes in the regulation of biologics: the performance of Codified potency tests and maintenance of challenge culture for the Codified potency tests. Options for reducing animal use in these processes were explored in a plenary lecture at the "International Workshop on Alternative Methods for Leptospira Vaccine Potency Testing: State of the Science and the Way Forward" held at the Center for Veterinary Biologics in September 2012. The use of validated in vitro potency assays such as those developed by the U.S. Department of Agriculture for Leptospira (L.) canicola, Leptospira grippotyphosa, Leptospira pomona, and Leptospira icterohaemorrhagiae rather than the Codified hamster vaccination-challenge assay was encouraged. Alternatives such as reduced animal numbers in the hamster vaccination-challenge testing were considered for problematic situations. Specifically, the merits of sharing challenge controls, reducing group sizes, and eliminating animals for concurrent challenge dose titration were assessed. Options for maintaining virulent, stable cultures without serial passage through hamsters or with decreased hamster use were also discussed. The maintenance of virulent Leptospira without the use of live animals is especially difficult since a reliable means to maintain virulence after multiple in vitro passages has not yet been identified. Published by Elsevier Ltd.

  12. Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency.

    Science.gov (United States)

    De Lucca, George V; Kim, Ui Tae; Vargo, Brian J; Duncia, John V; Santella, Joseph B; Gardner, Daniel S; Zheng, Changsheng; Liauw, Ann; Wang, Zhang; Emmett, George; Wacker, Dean A; Welch, Patricia K; Covington, Maryanne; Stowell, Nicole C; Wadman, Eric A; Das, Anuk M; Davies, Paul; Yeleswaram, Swamy; Graden, Danielle M; Solomon, Kimberly A; Newton, Robert C; Trainor, George L; Decicco, Carl P; Ko, Soo S

    2005-03-24

    Starting with our previously described(20) class of CC chemokine receptor-3 (CCR3) antagonist, we improved the potency by replacing the phenyl linker of 1 with a cyclohexyl linker and by replacing the 4-benzylpiperidine with a 3-benzylpiperidine. The resulting compound, 32, is a potent and selective antagonist of CCR3. SAR studies showed that the 3-acetylphenyl urea of 32 could be replaced with heterocyclic ureas or heterocyclic-substituted phenyl ureas and still maintain the potency (inhibition of eotaxin-induced chemotaxis) of this class of compounds in the low-picomolar range (IC(50) = 10-60 pM), representing some of the most potent CCR3 antagonists reported to date. The potency of 32 for mouse CCR3 (chemotaxis IC(50) = 41 nM) and its oral bioavailability in mice (20% F ) were adequate to assess the efficacy in animal models of allergic airway inflammation. Oral administration of 32 reduced eosinophil recruitment into the lungs in a dose-dependent manner in these animal models. On the basis of its overall potency, selectivity, efficacy, and safety profile, the benzenesulfonate salt of 32, designated DPC168, entered phase I clinical trials.

  13. 75 FR 8937 - Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PAH...

    Science.gov (United States)

    2010-02-26

    ... AGENCY Development of a Relative Potency Factor (RPF) Approach for Polycyclic Aromatic Hydrocarbon (PAH...) Approach for Polycyclic Aromatic Hydrocarbon (PAH) Mixtures'' (EPA/635/R-08/012A). The draft document was... 27, 2010. The listening session on the draft document for PAH mixtures will be held on April 7,...

  14. In vitro screening of the endocrine disrupting potency of brominated flame retardants and their metabolites

    Energy Technology Data Exchange (ETDEWEB)

    Hamers, T.; Kamstra, J.H. [Inst. for Environmental Studies (IVM), Amsterdam (Netherlands); Sonneveld, E. [BioDetection Systems (BDS), Amsterdam (Netherlands); Murk, A.J. [Wageningen Univ., Toxicology Group, Wageningen (Netherlands); Zegers, B.N.; Boon, J.P. [Royal Netherlands Inst. for Sea Research (NIOZ), Den Burg (Netherlands); Brouwer, A. [Umea Univ., Umea (Sweden)

    2004-09-15

    Substantial evidence is recently becoming available that brominated flame retardants (BFRs) are potential endocrine disruptors. The toxicological profile of BFRs, however, is too incomplete and insufficient to perform human and ecological risk assessment. To fill these gaps, the EU funded research program FIRE was started in December 2002. This program aims at the identification and toxicological characterization of the most potent and environmentally relevant BFRs and their possible risk for human and wildlife health. As part of a hazard identification approach, twenty seven BFRs have been selected within the framework of FIRE for pre-screening their endocrinedisrupting potencies. Selection of test compounds was based on a maximal variation in physicochemical characteristics of BFRs within the test set, allowing the establishment of quantitative structure-activity relationships (QSARs). In addition, environmental relevance (e.g. high production volumes and persistence) and availability for testing were used as selection criteria. BFRs were tested in seven different in vitro bioassays for their potency to interfere via estrogenic, thyroidal, androgenic, progestagenic, and Ah-receptor mediated pathways. Metabolisation rates of BFRs were determined using phenobarbital-induced rat liver microsomes. Finally, the endocrine disrupting potency of the metabolites was determined in the same in vitro bio-assays and compared to the potency of the parent compounds.

  15. Validation of self-reported cannabis dose and potency: an ecological study

    NARCIS (Netherlands)

    van der Pol, P.; Liebregts, N.; de Graaf, R.; Korf, D.J.; van den Brink, W.; van Laar, M.

    2013-01-01

    Aims To assess the reliability and validity of self-reported cannabis dose and potency measures. Design Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Setting Ecological study with assessments at

  16. Replacing the NIH test for rabies vaccine potency testing: a synopsis of drivers and barriers

    NARCIS (Netherlands)

    Schiffelers, M.J.; Blaauboer, B.J.; Bakker, W.; Hendriksen, C.F.M.

    2014-01-01

    Approximately 70% of animal use is utilized to demonstrate quality control of vaccines. Especially rabies vaccine potency testing, using the NIH challenge test, involves objections in terms of scientific relevance, animal welfare concern and costs. Several 3R models have been proposed to refine, red

  17. Benzothiophene inhibitors of MK2. Part 2: improvements in kinase selectivity and cell potency.

    Science.gov (United States)

    Anderson, David R; Meyers, Marvin J; Kurumbail, Ravi G; Caspers, Nicole; Poda, Gennadiy I; Long, Scott A; Pierce, Betsy S; Mahoney, Matthew W; Mourey, Robert J; Parikh, Mihir D

    2009-08-15

    Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.

  18. Benzothiophene inhibitors of MK2. Part 2: Improvements in kinase selectivity and cell potency

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, David R.; Meyers, Marvin J.; Kurumbail, Ravi G.; Caspers, Nicole; Poda, Gennadiy I.; Long, Scott A.; Pierce, Betsy S.; Mahoney, Matthew W.; Mourey, Robert J.; Parikh, Mihir D.; Pfizer

    2010-10-01

    Optimization of kinase selectivity for a set of benzothiophene MK2 inhibitors provided analogs with potencies of less than 500 nM in a cell based assay. The selectivity of the inhibitors can be rationalized by examination of X-ray crystal structures of inhibitors bound to MK2.

  19. Social Capital, Team Efficacy and Team Potency: The Mediating Role of Team Learning Behaviors

    Science.gov (United States)

    van Emmerik, Hetty; Jawahar, I. M.; Schreurs, Bert; de Cuyper, Nele

    2011-01-01

    Purpose: Drawing on social capital theory and self-identification theory, this study aims to examine the associations of two indicators of social capital, personal networks and deep-level similarity, with team capability measures of team efficacy and team potency. The central focus of the study is to be the hypothesized mediating role of team…

  20. Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies.

    Science.gov (United States)

    Webb, Nicholas E; Montefiori, David C; Lee, Benhur

    2015-09-29

    A new generation of HIV broadly neutralizing antibodies (bnAbs) with remarkable potency, breadth and epitope diversity has rejuvenated interest in immunotherapeutic strategies. Potencies defined by in vitro IC50 and IC80 values (50 and 80% inhibitory concentrations) figure prominently into the selection of clinical candidates; however, much higher therapeutic levels will be required to reduce multiple logs of virus and impede escape. Here we predict bnAb potency at therapeutic levels by analysing dose-response curve slopes, and show that slope is independent of IC50/IC80 and specifically relates to bnAb epitope class. With few exceptions, CD4-binding site and V3-glycan bnAbs exhibit slopes >1, indicative of higher expected therapeutic effectiveness, whereas V2-glycan, gp41 membrane-proximal external region (MPER) and gp120-gp41 bnAbs exhibit less favourable slopes <1. Our results indicate that slope is one major predictor of both potency and breadth for bnAbs at clinically relevant concentrations, and may better coordinate the relationship between bnAb epitope structure and therapeutic expectations.

  1. Botulinum neurotoxin serotype A specific cell-based potency assay to replace the mouse bioassay.

    Science.gov (United States)

    Fernández-Salas, Ester; Wang, Joanne; Molina, Yanira; Nelson, Jeremy B; Jacky, Birgitte P S; Aoki, K Roger

    2012-01-01

    Botulinum neurotoxin serotype A (BoNT/A), a potent therapeutic used to treat various disorders, inhibits vesicular neurotransmitter exocytosis by cleaving SNAP25. Development of cell-based potency assays (CBPAs) to assess the biological function of BoNT/A have been challenging because of its potency. CBPAs can evaluate the key steps of BoNT action: receptor binding, internalization-translocation, and catalytic activity; and therefore could replace the current mouse bioassay. Primary neurons possess appropriate sensitivity to develop potential replacement assays but those potency assays are difficult to perform and validate. This report describes a CBPA utilizing differentiated human neuroblastoma SiMa cells and a sandwich ELISA that measures BoNT/A-dependent intracellular increase of cleaved SNAP25. Assay sensitivity is similar to the mouse bioassay and measures neurotoxin biological activity in bulk drug substance and BOTOX® product (onabotulinumtoxinA). Validation of a version of this CBPA in a Quality Control laboratory has led to FDA, Health Canada, and European Union approval for potency testing of BOTOX®, BOTOX® Cosmetic, and Vistabel®. Moreover, we also developed and optimized a BoNT/A CBPA screening assay that can be used for the discovery of novel BoNT/A inhibitors to treat human disease.

  2. Detection of estrogenic potency in wastewater and surface water with three in vitro bioassays

    NARCIS (Netherlands)

    Murk, A.J.; Legler, J.; Lipzig, van M.M.H.; Meerman, J.H.N.; Belfroid, A.C.; Spenkelink, A.; Burg, van der B.; Rijs, G.B.J.; Vethaak, D.

    2002-01-01

    A study was performed to optimize sample preparation and application of three in vitro assays for measuring estrogenic potency in environmental extracts. The three assays applied were an estrogen receptor (ER)-binding assay and two reporter gene effect assays: a yeast estrogen screen (YES) and the E

  3. Antipsychotic-induced extrapyramidal syndromes - Risperidone compared with low- and high-potency conventional antipsychotic drugs

    NARCIS (Netherlands)

    Schillevoort, [No Value; de Boer, A; Herings, RMC; Roos, RAC; Jansen, PAF; Leufkens, HGM

    2001-01-01

    Aim: To compare the risk of extrapyramidal syndromes (EPS) between patients using risperidone and those using low-potency conventional antipsychotic drugs (APDs) in outpatient clinical practice, as measured by the use of anticholinergic medication. We tried to replicate results from previous clinica

  4. Development of an Innovative in Vitro Potency Assay for Anti-Botulinum Antitoxins.

    Science.gov (United States)

    Rosen, Osnat; Ozeri, Eyal; Barnea, Ada; David, Alon Ben; Zichel, Ran

    2016-09-24

    Botulinum neurotoxins are bacterial proteins that cause botulism, a life-threatening disease. Therapy relies mostly on post-intoxication antibody treatment. The only accepted method to measure the potency of, and to approve, antitoxin preparations is the mouse lethality neutralization bioassay. However, this assay is time-consuming, labor-intensive, costly, and raises ethical issues related to the large numbers of laboratory animals needed. Until now, all efforts to develop an alternative in vitro assay have not provided a valid replacement to the mouse potency assay. In the present study, we report the development of an innovative in vitro assay for determining botulinum antitoxin potency, using botulinum type B as a model. The concept of the assay is to mimic two fundamental steps in botulinum intoxication: receptor binding and catalytic activity. By simulating these steps in vitro we were able to accurately determine the potency of antitoxin preparations. The reproducibility of the assay was high with a CV vitro assay highly correlated with that measured by the standard in vivo mouse assay (r = 0.9842, p vitro assay has the potential to be considered, after validation, as a replacement to the mouse assay for quantitating neutralizing antibody concentrations in pharmaceutical botulinum antitoxin preparations. Future adoption of this in vitro assay would minimize the use of laboratory animals, speed up the time, and reduce the cost of botulinum antitoxin approval.

  5. 我院门诊喹诺酮类药物临床应用调查%Investigation on Clinical Use of Quinolones in Outpatient Clinic

    Institute of Scientific and Technical Information of China (English)

    田雪莉; 周霞

    2011-01-01

    Objective To understand the use status of quinolone- related drugs in the outpatient clinic for standardizing rational drug use in clinic. Methods The prescriptions involving quinolone- related drugs in the outpatient clinic were extracted and statistically analyzed in aspects of disease category, age, drug variety and rationality of drug use. Results Quinolone medication accounted for 21.50% of all antibiotic uses in the outpatient clinic. 43.06% of quinolones were used for respiratory diseases. Among them, levofloxacin had the highest use frequency(48.79% ). Unreasonable prescriptions included the use of quinolones for the patients yomger than 18 years old and without clear diagnosis of infectious diseases. Conclusion Quinolones are commonly used in anti- infection treatment in the outpatient clinic. The use indicators are rationally grasped as a whole. But using quinolones in children still exists, which should be needed to pay attention. The dosage in different ages has no apparent difference. The medieation dose in elderly patients should be adjusted.%目的 了解医院门诊喹诺酮类药物的使用情况,规范临床合理用药.方法 抽取喹诺酮类药物的处方,从痛种、患者年龄、用药品种、用药合理性等方面进行统计分析.结果 喹诺酮类药物的使用占全部抗茵药物的21.50%,43.06%用于呼吸系统疾病,其中左氧氟沙星使用频率最高(占喹诺酮类的48.79%).不合理用药包括18岁以下儿童用药、无感染性疾病诊断用药等.结论 喹诺酮类药物在医院门诊抗感染治疗中比较常见,应用指征掌握基本合理,但仍存在儿童用药,应予以重视.不同年龄用量差异不明显,对老年患者用药应进行剂量调整.

  6. Characterization of CTX-M enzymes, quinolone resistance determinants, and antimicrobial residues from hospital sewage, wastewater treatment plant, and river water.

    Science.gov (United States)

    Conte, Danieli; Palmeiro, Jussara Kasuko; da Silva Nogueira, Keite; de Lima, Thiago Marenda Rosa; Cardoso, Marco André; Pontarolo, Roberto; Degaut Pontes, Flávia Lada; Dalla-Costa, Libera Maria

    2017-02-01

    Multidrug-resistant (MDR) bacteria are widespread in hospitals and have been increasingly isolated from aquatic environments. The aim of the present study was to characterize extended-spectrum β-lactamase (ESBL) and quinolone-resistant Enterobacteriaceae from a hospital effluent, sanitary effluent, inflow sewage, aeration tank, and outflow sewage within a wastewater treatment plant (WWTP), as well as river water upstream and downstream (URW and DRW, respectively), of the point where the WWTP treated effluent was discharged. β-lactamase (bla) genes, plasmid-mediated quinolone resistance (PMQR), and quinolone resistance-determining regions (QRDRs) were assessed by amplification and sequencing in 55 ESBL-positive and/or quinolone-resistant isolates. Ciprofloxacin residue was evaluated by high performance liquid chromatography. ESBL-producing isolates were identified in both raw (n=29) and treated (n=26) water; they included Escherichia coli (32), Klebsiella pneumoniae (22) and Klebsiella oxytoca (1). Resistance to both cephalosporins and quinolone was observed in 34.4% of E. coli and 27.3% of K. pneumoniae. Resistance to carbapenems was found in 5.4% of K. pneumoniae and in K. oxytoca. Results indicate the presence of blaCTX-M (51/55, 92.7%) and blaSHV (8/55, 14.5%) ESBLs, and blaGES (2/55, 3.6%) carbapenemase-encoding resistance determinants. Genes conferring quinolone resistance were detected at all sites, except in the inflow sewage and aeration tanks. Quinolone resistance was primarily attributed to amino acid substitutions in the QRDR of GyrA (47%) or to the presence of PMQR (aac-(6')-Ib-cr, oqxAB, qnrS, and/or qnrB; 52.9%) determinants. Ciprofloxacin residue was absent only from URW. Our results have shown strains carrying ESBL genes, PMQR determinants, and mutations in the gyrA QRDR genes mainly in hospital effluent, URW, and DRW samples. Antimicrobial use, and the inefficient removal of MDR bacteria and antibiotic residue during sewage treatment, may

  7. Functional potencies of dopamine agonists and antagonists at human dopamine D₂ and D₃ receptors.

    Science.gov (United States)

    Tadori, Yoshihiro; Forbes, Robert A; McQuade, Robert D; Kikuchi, Tetsuro

    2011-09-01

    We measured the functional agonist potencies of dopamine agonists including antiparkinson drugs, and functional antagonist potencies of antipsychotics at human dopamine D(2) and D(3) receptors. In vitro pharmacological assessment included inhibition of forskolin-stimulated cAMP accumulation and the reversal of dopamine-induced inhibition in clonal Chinese hamster ovary cells expressing low and high densities of human dopamine D(2L) and D(2S) receptors (hD(2L)-Low, hD(2L)-High, hD(2S)-Low and hD(2S)-High, respectively) and human dopamine D(3) Ser-9 and D(3) Gly-9 receptors (hD(3)-Ser-9 and hD(3)-Gly-9, respectively). Cabergoline, bromocriptine, pergolide, (±)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), talipexole, pramipexole, R-(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano[4,3-b]-1,4-oxazin-9-olhydrochloride (PD128907) and ropinirole behaved as dopamine D(2) and D(3) receptor full agonists and showed higher potencies in hD(2L)-High and hD(2S)-High compared to hD(2L)-Low and hD(2S)-Low. In hD(3)-Ser-9 and hD(3)-Gly-9 compared to hD(2L)-Low and hD(2S)-Low, dopamine, ropinirole, PD128907, and pramipexole potencies were clearly higher; talipexole and 7-OH-DPAT showed slightly higher potencies; pergolide showed slightly lower potency; and, cabergoline and bromocriptine potencies were lower. Aripiprazole acted as an antagonist in hD(2L)-Low; a low intrinsic activity partial agonist in hD(2S)-Low; a moderate partial agonist in hD(3)-Ser-9 and hD(3)-Gly-9; a robust partial agonist in hD(2L)-High; and a full agonist in hD(2S)-High. Amisulpride, sulpiride and perphenazine behaved as preferential antagonists; and chlorpromazine and asenapine behaved as modest preferential antagonists; whereas fluphenazine, haloperidol, and blonanserin behaved as non-preferential antagonists in hD(2S)-Low and hD(2S)-High compared to hD(3)-Ser-9 and hD(3)-Gly-9. These findings may help to elucidate the basis of therapeutic benefit observed with these drugs, with

  8. Multiplex Assay for Protein Profiling and Potency Measurement of German Cockroach Allergen Extracts.

    Directory of Open Access Journals (Sweden)

    Taruna Khurana

    Full Text Available German cockroach (GCr allergens induce IgE responses and may cause asthma. Commercial GCr allergen extracts are variable and existing assays may not be appropriate for determining extract composition and potency.Our aim was to develop a multiplex antibody/bead-based assay for assessment of GCr allergen extracts.Single chain fragment variable (scFv antibodies against GCr were obtained by screening libraries derived from naïve human lymphocytes and hyperimmunized chicken splenocytes and bone marrow. Selected clones were sequenced and characterized by immunoblotting. Eighteen scFv antibodies (17 chicken, 1 human coupled to polystyrene beads were used in this suspension assay; binding of targeted GCr allergens to antibody-coated beads was detected using rabbit antisera against GCr, and against specific allergens rBla g 1, rBla g 2, and rBla g 4. The assay was tested for specificity, accuracy, and precision. Extracts were also compared by IgE competition ELISA.Chicken scFv's generated eight different binding patterns to GCr proteins from 14 to 150 kDa molecular weight. Human scFv's recognized a 100 kDa GCr protein. The multiplex assay was found to be specific and reproducible with intra-assay coefficient of variation (CV of 2.64% and inter-assay CV of 10.0%. Overall potencies of various GCr extracts were calculated using mean logEC50s for eight selected scFvs. Overall potency measures were also analyzed by assessing the contributions to potency of each target.An scFv antibody-based multiplex assay has been developed capable of simultaneously measuring different proteins in a complex mixture, and to determine the potencies and compositions of allergen extracts.

  9. Validation of self-reported cannabis dose and potency: an ecological study.

    Science.gov (United States)

    van der Pol, Peggy; Liebregts, Nienke; de Graaf, Ron; Korf, Dirk J; van den Brink, Wim; van Laar, Margriet

    2013-10-01

    To assess the reliability and validity of self-reported cannabis dose and potency measures. Cross-sectional study comparing self-reports with objective measures of amount of cannabis and delta-9-tetrahydrocannabinol (THC) concentration. Ecological study with assessments at participants' homes or in a coffee shop. Young adult frequent cannabis users (n = 106) from the Dutch Cannabis Dependence (CanDep) study. The objectively measured amount of cannabis per joint (dose in grams) was compared with self-reported estimates using a prompt card and average number of joints made from 1 g of cannabis. In addition, objectively assessed THC concentration in the participant's cannabis was compared with self-reported level of intoxication, subjective estimate of cannabis potency and price per gram of cannabis. Objective estimates of doses per joint (0.07-0.88 g/joint) and cannabis potency (1.1-24.7%) varied widely. Self-reported measures of dose were imprecise, but at group level, average dose per joint was estimated accurately with the number of joints made from 1 g [limit of agreement (LOA) = -0.02 g, 95% confidence interval (CI) = -0.29; 0.26], whereas the prompt card resulted in serious underestimation (LOA = 0.14 g, 95% CI = -0.10; 0.37). THC concentration in cannabis was associated with subjective potency ['average' 3.77% (P = 0.002) and '(very) strong' 5.13% more THC (P < 0.001) than '(very) mild' cannabis] and with cannabis price (about 1% increase in THC concentration per euro spent on 1 g of cannabis, P < 0.001), but not with level of intoxication. Self-report measures relating to cannabis use appear at best to be associated weakly with objective measures. Of the self-report measures, number of joints per gram, cannabis price and subjective potency have at least some validity. © 2013 Society for the Study of Addiction.

  10. Effect of sugar positions in ginsenosides and their inhibitory potency on Na+/K+-ATPase activity

    Institute of Scientific and Technical Information of China (English)

    Ronald JY CHEN; Tse-yu CHUNG; Feng-yin LI; Nan-hei LIN; Jason TC TZEN

    2009-01-01

    Aim: To determine whether ginsenosides with various sugar attachments may act as active components responsible for the cardiac therapeutic effects of ginseng and sanqi (the roots of Panax ginseng and Panax notoginseng) via the same molecular mechanism triggered by cardiac glycosides, such as ouabain and digoxin. Methods: The structural similarity between ginsenosides and ouabain was analyzed. The inhibitory potency of ginseno-sides and ouabain on Na+/K+-ATPase activity was examined and compared. Molecular modeling was exhibited for the docking of ginsenosides to Na+/K+-ATPase. Results: Ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure, equivalent to the sugar position in cardiac glycosides, and possessed inhibitory potency on Na+/K+-ATPase activity. However, their inhibi-tory potency was significantly reduced or completely abolished when a monosaccharide was linked to the C-6 or C-20 posi-tion of the steroid-like structure; replacement of the monosaccharide with a disaccharide molecule at either of these posi-tions caused the disappearance of the inhibitory potency. Molecular modeling and docking confirmed that the difference in Na+/K+-ATPase inhibitory potency among ginsenosides was due to the steric hindrance of sugar attachment at the C-6 and C-20 positions of the steroid-like structure. Conclusion: The cardiac therapeutic effects of ginseng and sanqi should be at least partly attributed to the effective inhi-bition of Na+/K+-ATPase by their metabolized ginsenosides with sugar moieties attached only to the C-3 position of the steroid-like structure.

  11. Detection of estrogenic potency in wastewater and surface water with three in vitro bioassays.

    Science.gov (United States)

    Murk, Albertinka J; Legler, Juliette; van Lipzig, Marola M H; Meerman, John H N; Belfroid, Angelique C; Spenkelink, Albertus; van der Burg, Bart; Rijs, Gerard B J; Vethaak, Dick

    2002-01-01

    A study was performed to optimize sample preparation and application of three in vitro assays for measuring estrogenic potency in environmental extracts. The three assays applied were an estrogen receptor (ER)-binding assay and two reporter gene effect assays: a yeast estrogen screen (YES) and the ER-mediated chemically activated luciferase gene expression (ER-CALUX) assay. All assays were able to detect estrogenicity, but the amounts of material needed for the assays differed greatly between the three assays (ER-binding assay > YES > ER-CALUX). In addition, in the ER-binding assay, both agonists and antagonists give an estrogenic response, resulting in higher estradiol equivalency (EEQ) levels than both the ER-CALUX and the YES assay for the same samples. The EEQs found in wastewater treatment plants (WTPs) with the ER-CALUX assay were in the range of 4 to 440 and 0.11 to 59 pmol/L for influent and effluent, respectively. Water extracts from four large rivers had levels ranging from 0.25 to 1.72 pmol/L. Extracts from suspended matter and sludge contained estrogenic potency of 0.26 to 2.49 and 1.6 to 41 pmol EEQ/g dry weight, respectively. In WTPs, the average reduction of estrogenic potency in effluent compared to influent was 90 to 95% in municipal WTPs and about 50% in industrial WTPs. In influent, 30% of the ER-CALUX activity could not be explained by the calculated potencies based on chemical analysis of a number of known (xeno)estrogens; in effluent the unexplained fraction was 80%. These first results of analyzing estrogenic potency in WTP water and surface water in The Netherlands indicate that further studies are warranted to investigate the actual risks for aquatic systems.

  12. Estrogenic potencies of several environmental pollutants, as determined by vitellogenin induction in a carp hepatocyte assay.

    Science.gov (United States)

    Smeets, J M; van Holsteijn, I; Giesy, J P; Seinen, W; van den Berg, M

    1999-08-01

    Estrogenic potencies of several xenoestrogens were determined in vitro, using cultured hepatocytes from a genetically uniform male carp strain (Cyprinus carpio). Estrogenicity was measured as induction of the yolk protein precursor vitellogenin (Vtg), and compared to Vtg induction by 17beta-estradiol (E2). The order of estrogenic potency was: methoxychlor (MXCL) > o,p-DDT > chlordecone approximately/= bisphenol-A approximately/= 4-t-pentylphenol. Estrogenic potencies of these compounds varied from 1 x 10(-3) to 1 x 10(-4) relative to E2. The synthetic estrogen DES had a relative estrogenic potency of 0.5, whereas dieldrin, beta-endosulfan, o,p-DDE, and toxaphene (technical mixture) did not induce vitellogenesis at concentrations up to 100 microM. Experiments in which cells were simultaneously exposed to E2 and these xenoestrogens showed that the Vtg-inducing activities of E2 and 4-t-pentylphenol or bisphenol-A were (partially) additive, whereas E2 antagonized the estrogenic effects of MXCL and o,p-DDT. The effect of cytochrome P4501A (CYP1A)-induction on the estrogenicity of MXCL was studied by co-exposing cells to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD (10 pM) caused a greater than 50-fold induction of CYP1A, measured as ethoxyresorufin O-deethylase (EROD) activity, but Vtg induction by MXCL was not significantly affected. This indicates that CYP1A is not involved in the bioactivation of MXCL to more potent estrogenic metabolites in carp. The CARP-HEP (hepatocyte) assay can detect xenoestrogens with a potency > or = 2 x 10(-5) relative to E2. It allows simultaneous testing of more than 10 compounds for both estrogenic and antiestrogenic effects, which makes it a promising tool for the screening of suspected xenoestrogens.

  13. A QSAR for the Mutagenic Potencies of Twelve 2-Amino-trimethylimidazopyridine Isomers: Structural, Quantum Chemical,and Hydropathic Factors

    Energy Technology Data Exchange (ETDEWEB)

    Knize, M G; Hatch, F T; Tanga, M J; Lau, E V; Colvin, M E

    2005-04-23

    An isomeric series of heterocyclic amines related to one found in heated muscle meats was investigated for properties that predict their measured mutagenic potency. Eleven of the 12 possible 2-amino-trimethylimidazopyridine (TMIP) isomers were tested for mutagenic potency in the Ames/Salmonella test with bacterial strain TA98, and resulted in a 600-fold range in potency. Structural, quantum chemical and hydropathic data were calculated on the parent molecules and the corresponding nitrenium ions of all of the tested isomers to establish models for predicting the potency of the unknown isomer. The regression model accounting for the largest fraction of the total variance in mutagenic potency contains four predictor variables: dipole moment, a measure of the gap between amine LUMO and HOMO energies, percent hydrophilic surface, and energy of amine LUMO. The most important determinants of high mutagenic potency in these amines are: (1) a small dipole moment, (2) the combination of b-face ring fusion and N3-methyl group, and (3) a lower calculated energy of the {pi} electron system. Based on predicted potency from the average of five models, the isomer not yet synthesized and tested is expected to have a mutagenic potency of 0.84 revertants/{micro}g in test strain TA98.

  14. Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular potency.

    Science.gov (United States)

    Anderson, David R; Meyers, Marvin J; Kurumbail, Ravi G; Caspers, Nicole; Poda, Gennadiy I; Long, Scott A; Pierce, Betsy S; Mahoney, Matthew W; Mourey, Robert J

    2009-08-15

    Identification of potent benzothiophene inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2), structure-activity relationship (SAR) studies, selectivity assessments against CDK2, cellular potency and mechanism of action are presented. Crystallographic data provide a rationale for the observed MK2 potency as well as selectivity over CDK2 for this class of inhibitors.

  15. Estrogenic and esterase-inhibiting potency in rainwater in relation to pesticide concentrations, sampling season and location

    NARCIS (Netherlands)

    Hamers, T.H.M.; Brink, van den P.J.; Mos, L.; Linden, van der S.C.; Legler, J.; Koeman, J.H.; Murk, A.J.

    2003-01-01

    In a year-round monitoring program (1998), pesticide composition and toxic potency of the mix of pollutants present in rainwater were measured. The goal of the study was to relate atmospheric deposition of toxic potency and pesticide composition to each other and to sampling period and local

  16. Estrogenic and esterase-inhibiting potency in rainwater in relation to pesticide concentrations, sampling season and location

    NARCIS (Netherlands)

    Hamers, T.H.M.; Brink, van den P.J.; Mos, L.; Linden, van der S.C.; Legler, J.; Koeman, J.H.; Murk, A.J.

    2003-01-01

    In a year-round monitoring program (1998), pesticide composition and toxic potency of the mix of pollutants present in rainwater were measured. The goal of the study was to relate atmospheric deposition of toxic potency and pesticide composition to each other and to sampling period and local agricul

  17. Determination of relative potencies for chemical inhibition of spontaneous neuronal activity using a four amplifier MEA system.

    Science.gov (United States)

    Potency determination is important to identify the most promising drug candidates as well as identification of and ranking of compound toxicity. In our laboratory, we have utilized MEA recording techniques to determine the relative potency of 11 insecticidal compounds and rank th...

  18. Research progress on the metal complexes of quinolone drug ligands%金属与喹诺酮类药物构筑的配合物的研究进展

    Institute of Scientific and Technical Information of China (English)

    康新平; 安哲

    2012-01-01

    This article reviewed the development of the quinolone drug and the structure and potential activity of the quinolone drug metal complexes. Some suggestions of the quinolone drug metal complexes in-depth in the future were presented.%本文综述了喹诺酮类药物的发展过程,以及各种金属离子与该类药物构筑形成配合物晶体结构方面的研究进展,展望了此类研究的发展趋势.

  19. Mechanisms of quinolone resistance in Salmonella spp. / Mecanismos de resistência às quinolonas em Salmonella spp.

    Directory of Open Access Journals (Sweden)

    Tereza Cristina Rocha Moreira de Oliveira

    2010-07-01

    Full Text Available Salmonellosis is a common and widespread zoonotic disease of humans and a frequent cause of foodborne disease. Treatment of severe and systemic salmonellosis is usually done with fluoroquinolones. In this review resistance mechanisms of Salmonella to quinolones are discussed. Single point mutations in the quinolone resistant determining region (QRDR of the gyrA gene may be sufficient to generate high levels of resistance to non-fluorated quinolones and also may decrease the fluoroquinolones susceptibility. Other resistance mechanisms that should be considered are mutations in parC gene, the possibility of acquiring resistance through plasmidial transference and hyper-expression of efflux pumps. Fluoroquinolones resistance is still relatively uncommon in Salmonella compared to other species belonging to the Enterobacteriaceae family. However, the more careful use of fluoroquinolones in veterinary and human medicine is essential to decrease the selective pressure which can avoid the emergence and spread of resistant clones and consequently maintain the clinical efficacy of this group of antibiotics.A salmonelose é uma zoonose de importância mundial e uma das mais freqüentes doenças de origem alimentar. As fluoroquinolonas são a principal opção para o tratamento de salmoneloses graves ou sistêmicas. Esta revisão de literatura teve como objetivo apresentar os principais mecanismos envolvidos na resistência de Salmonella spp a estes antimicrobianos. Mutações de ponto na Região Determinante de Resistência à Quinolona (QRDR do gene gyrA podem gerar altos níveis de resistência a quinolonas não-fluoradas, além de reduzir a suscetibilidade as fluoroquinolonas. Outros mecanismos de resistência que também precisam ser considerados são as mutações no gene parC, a possibilidade do envolvimento de plasmídios de resistência e o sistema de efluxo ativo. A resistência às fluoroquinolonas ainda é incomum em Salmonella spp., quando

  20. Structure of the Dioxygenase AsqJ: Mechanistic Insights into a One-Pot Multistep Quinolone Antibiotic Biosynthesis

    KAUST Repository

    Bräuer, Alois

    2015-11-10

    © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. Multienzymatic cascades are responsible for the biosynthesis of natural products and represent a source of inspiration for synthetic chemists. The FeII/α-ketoglutarate-dependent dioxygenase AsqJ from Aspergillus nidulans is outstanding because it stereoselectively catalyzes both a ferryl-induced desaturation reaction and epoxidation on a benzodiazepinedione. Interestingly, the enzymatically formed spiro epoxide spring-loads the 6,7-bicyclic skeleton for non-enzymatic rearrangement into the 6,6-bicyclic scaffold of the quinolone alkaloid 4′-methoxyviridicatin. Herein, we report different crystal structures of the protein in the absence and presence of synthesized substrates, surrogates, and intermediates that mimic the various stages of the reaction cycle of this exceptional dioxygenase.

  1. Quinolone- and ß-lactam-resistance in Escherichia coli from Danish and Italian broiler flocks

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Guardabassi, Luca; Bisgaard, Magne

    , sock samples were collected from 10 parent flocks and 10 offspring flocks, according to the procedure currently used for the surveillance of Salmonella in the EU. Samples were enriched in McConkey broth and streaked on McConkey agar plates added with nalidixic acid (32 µg/ml), ciprofloxacin (2 µg...... on cephalosporin-resistant isolates. While resistance to ampicillin and nalidixic acid was widespread in both countries, resistance to ciprofloxacin and cephalosporins was more common among Italian flocks. In Denmark, ciprofloxacin resistance was only detected in one parent flock without any history of quinolone...... usage and none of the flocks was positive for cephalosporin-resistant E. coli. In Italy, resistance to ciprofloxacin was detected in all flocks and resistances to ceftiofur and cefotaxime were detected in five flocks. Primers specific for the CTX-M-type ESBLs generated PCR amplicons from isolates from...

  2. Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents.

    Science.gov (United States)

    Zhang, Ling; Addla, Dinesh; Ponmani, Jeyakkumar; Wang, Ao; Xie, Dan; Wang, Ya-Nan; Zhang, Shao-Lin; Geng, Rong-Xia; Cai, Gui-Xin; Li, Shuo; Zhou, Cheng-He

    2016-03-23

    A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 μM concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities.

  3. Optimal control of ultrafast laser driven many-electron dynamics in a polyatomic molecule: N-methyl-6-quinolone

    Science.gov (United States)

    Klamroth, Tillmann

    2006-04-01

    We report time-dependent configuration interaction singles calculations for the ultrafast laser driven many-electron dynamics in a polyatomic molecule, N-methyl-6-quinolone. We employ optimal control theory to achieve a nearly state-selective excitation from the S0 to the S1 state, on a time scale of a few (≈6) femtoseconds. The optimal control scheme is shown to correct for effects opposing a state-selective transition, such as multiphoton transitions and other, nonlinear phenomena, which are induced by the ultrashort and intense laser fields. In contrast, simple two-level π pulses are not effective in state-selective excitations when very short pulses are used. Also, the dependence of multiphoton and nonlinear effects on the number of states included in the dynamical simulations is investigated.

  4. Simultaneous determination of multiple (fluoro)quinolone antibiotics in food samples by a one-step fluorescence polarization immunoassay.

    Science.gov (United States)

    Mi, Tiejun; Wang, Zhanhui; Eremin, Sergei A; Shen, Jianzhong; Zhang, Suxia

    2013-10-02

    This paper describes a rapid one-step fluorescence polarization immunoassay (FPIA) for the simultaneous determination of multiple (fluoro)quinolone antibiotics (FQs) in food samples. Several fluorescent tracers were synthesized and evaluated in the FPIA method based on a broad-specificity of monoclonal antibodies toward FQs. The heterogeneous tracer, SAR-5-FAM, was considered as the optimal choice to prepare the immunocomplex single reagent, which allows a rapid and sensitive displacement reaction by addition of analytes. Optimized single-reagent FPIA exhibited broad cross-reactivities in the range of 7.8-172.2% with 16 FQs tested and was capable of determining most FQs at the level of maximum residue limits. Recoveries for spiked milk and chicken muscle samples were from 77.8 to 116%, with relative standard deviation lower than 17.4%. Therefore, this method could be applicable in routine screening analysis of multiple FQ residues in food samples.

  5. Adsorption of quinolone antibiotics in spherical mesoporous silica: Effects of the retained template and its alkyl chain length.

    Science.gov (United States)

    Liang, Zhijie; Zhaob, Zhiwei; Sun, Tianyi; Shi, Wenxin; Cui, Fuyi

    2016-03-15

    In this study, mesoporous silica (meso-silica) MCM-41 and those with the templates retained were synthesized and characterized. Adsorption capacities of the synthesized materials towards typical quinolone antibiotic pollutants, enrofloxacin and norfloxacin as representative, were investigated, and effects of the alkyl chain length of the templates on the adsorption capacity were evaluated. The results of this study indicated that the retained templates enhanced the adsorption capacities (Qmax) of the meso-silica MCM-41 toward hydrophobic enrofloxacin, but had an inhibitory effect on that towards hydrophilic norfloxacin, which were attributed to the hydrophobic inter-environment created by the long alkyl chains of the retained templates. Importantly, the adsorption capacity increased with the increase of the alkyl chain length of the retained templates. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Multidrug Resistance in Quinolone-Resistant Gram-Negative Bacteria Isolated from Hospital Effluent and the Municipal Wastewater Treatment Plant.

    Science.gov (United States)

    Vaz-Moreira, Ivone; Varela, Ana Rita; Pereira, Thamiris V; Fochat, Romário C; Manaia, Célia M

    2016-03-01

    This study is aimed to assess if hospital effluents represent an important supplier of multidrug-resistant (MDR) Gram-negative bacteria that, being discharged in the municipal collector, may be disseminated in the environment and bypassed in water quality control systems. From a set of 101 non-Escherichia coli Gram-negative bacteria with reduced susceptibility to quinolones, was selected a group of isolates comprised by those with the highest indices of MDR (defined as nonsusceptibility to at least one agent in six or more antimicrobial categories, MDR ≥6) or resistance to meropenem or ceftazidime (n = 25). The isolates were identified and characterized for antibiotic resistance phenotype, plasmid-mediated quinolone resistance (PMQR) genes, and other genetic elements and conjugative capacity. The isolates with highest MDR indices were mainly from hospital effluent and comprised ubiquitous bacterial groups of the class Gammaproteobacteria, of the genera Aeromonas, Acinetobacter, Citrobacter, Enterobacter, Klebsiella, and Pseudomonas, and of the class Flavobacteriia, of the genera Chryseobacterium and Myroides. In this group of 25 strains, 19 identified as Gammaproteobacteria harbored at least one PMQR gene (aac(6')-Ib-cr, qnrB, qnrS, or oqxAB) or a class 1 integron gene cassette encoding aminoglycoside, sulfonamide, or carbapenem resistance. Most of the E. coli J53 transconjugants with acquired antibiotic resistance resulted from conjugation with Enterobacteriaceae. These transconjugants demonstrated acquired resistance to a maximum of five classes of antibiotics, one or more PMQR genes and/or a class 1 integron gene cassette. This study shows that ubiquitous bacteria, other than those monitored in water quality controls, are important vectors of antibiotic resistance and can be disseminated from hospital effluent to aquatic environments. This information is relevant to support management options aiming at the control of this public health problem.

  7. Occurrence of plasmid-mediated quinolone resistance and virulence genes in avian Escherichia coli isolates from Algeria.

    Science.gov (United States)

    Laarem, Meradi; Barguigua, Abouddihaj; Nayme, Kaotar; Akila, Abdi; Zerouali, Khalid; El Mdaghri, Naima; Timinouni, Mohammed

    2017-02-28

    The emergence and spread of quinolone-resistant Escherichia coli in poultry products puts consumers at risk of exposure to the strains of E. coli that resist antibiotic treatment. The objective of this study was to define the prevalence and virulence potential of poultry-associated nalidixic acid (NAL)-resistant E. coli in the Annaba city, Algeria. In total, 33 samples of retail chicken meat were purchased from various butcher shops and examined for bacterial contamination with NAL-resistant E. coli. These isolates were subjected to antimicrobial susceptibility testing and were also investigated for the presence of plasmid-mediated quinolone resistance (PMQR) genes and virulence genes using conventional polymerase chain reaction (PCR) and DNA sequencing. Phylogenetic grouping of the NAL-resistant E. coli isolates was determined by the conventional multiplex PCR method. Twenty-nine (87.8%) products yielded NAL-resistant E. coli. Antibiograms revealed that 96.55% of NAL-resistant E. coli isolates were multidrug resistant (MDR). Resistance was most frequently observed against sulfamethoxazole-trimethoprim (96.6%), tetracycline (96.6%), ciprofloxacin (72%), and amoxicillin (65.5%). Group A was the most prevalent phylogenetic group, followed by groups D, B1, and B2. The PMQR determinants were detected in three isolates with qnrB72 and qnrS1 type identified. Four (13.8%) isolates carried one of the Shiga toxin E. coli-associated genes stx1, stx2, and ehxA alleles. The high prevalence of NAL-resistant E. coli isolated from retail chicken meat with detection of MDR E. coli harboring Shiga toxin genes in this study gives a warning signal for possible occurrence of foodborne infections with failure in antibiotic treatment.

  8. Quinolone resistant Aeromonas spp. as carriers and potential tracers of acquired antibiotic resistance in hospital and municipal wastewater.

    Science.gov (United States)

    Varela, Ana Rita; Nunes, Olga C; Manaia, Célia M

    2016-01-15

    Members of the genus Aeromonas are recognized carriers of antibiotic resistance in aquatic environments. However, their importance on the spread of resistance from hospital effluents to the environment is poorly understood. Quinolone resistant Aeromonas spp. (n = 112) isolated from hospital effluent (HE) and from raw (RWW) and treated wastewater (TWW) of the receiving urban wastewater treatment plant (UWTP) were characterized. Species identification and genetic intraspecies diversity were assessed based on the 16S rRNA, cpn60 and gyrB genes sequence analysis. The antibiotic resistance phenotypes and genotypes (qnrA, qnrB, qnrC, qnrD, qnrS, qnrVC; qepA; oqxAB; aac(6′)-Ib-cr; blaOXA; incU) were analyzed in function of the origin and taxonomic group. Most isolates belonged to the species Aeromonas caviae and Aeromonas hydrophila (50% and 41%, respectively). The quinolone and the beta-lactamase resistance genes aac(6′)-Ib-cr and blaOXA, including gene blaOXA-101, identified for the first time in Aeromonas spp., were detected in 58% and 56% of the isolates, respectively, with identical prevalence in HE and UWTP wastewater. In contrast, the gene qnrS2 was observed mainly in isolates from the UWTP (51%) and rarely in HE isolates (3%), suggesting that its origin is not the clinical setting. Bacterial groups and genes that allow the identification of major routes of antibiotic resistance dissemination are valuable tools to control this problem. In this study, it was concluded that members of the genus Aeromonas harboring the genes aac(6′)-Ib-cr and blaOXA are relevant tracers of antibiotic resistance dissemination in wastewater habitats, while those yielding the gene qnrS2 allow the traceability from non-clinical sources.

  9. Hydrophilicity of quinolones is not an exclusive factor for decreased activity in efflux-mediated resistant mutants of Staphylococcus aureus.

    Science.gov (United States)

    Takenouchi, T; Tabata, F; Iwata, Y; Hanzawa, H; Sugawara, M; Ohya, S

    1996-08-01

    The elevated expression of the norA gene is responsible for efflux-mediated resistance to quinolones in Staphylococcus aureus (E.Y.W. Ng, M. Trucksis, and D.C. Hooper, Antimicrob. Agents Chemother. 38:1345-1355, 1994). For S. aureus transformed with a plasmid containing the cloned norA gene, SA113(pTUS20) (H. Yoshida, M. Bogaki, S. Nakamura, K. Ubukata, and M. Konno, J. Bacteriol. 172:6942-6949, 1990), and an overexpressed mutant, SA-1199B (G.W. Kaatz, S.M. Seo, and C.A. Ruble, J. Infect. Dis. 163:1080-1086, 1991), the MICs of norfloxacin increased 16 and 64 times compared with its MICs for the recipient and wild-type strains, SA113 and SA-1199, respectively. MICs of CS-940, however, increased only two and eight times, even though these two fluoroquinolones are similarly hydrophilic (apparent logPs of approximately -1). No good correlation was found, among 15 developed and developing quinolones, between the increment ratio in MICs and hydrophobicity (r = 0.61). Analysis of the quantitative structure-activity relationship among 40 fluoroquinolones revealed that the MIC increment ratio was significantly correlated with the bulkiness of the C-7 substituent and bulkiness and hydrophobicity of the C-8 substituent of fluoroquinolones (r = 0.87) and not with its molecular hydrophobicity (r = 0.47). Cellular accumulation of norfloxacin in SA-1199B was significantly lower than that in SA-1199, and it was increased by addition of carbonyl cyanide m-chlorophenyl hydrazone. On the other hand, accumulations of CS-940 in these strains were nearly identical, and they were not affected by addition of the protonophore.

  10. Shyntesis and cytotoxicity evaluation in vitro of new compounds with hybrid structures of 8-flavoneacetic acid and quinolones; Sintesis y evaluacion citotoxica in vitro de nuevos compuestos con estructuras hibridas del acido 8-flavonacetico quinolonas

    Energy Technology Data Exchange (ETDEWEB)

    Biaa, M.F.; Castellano, J.M.; Emling, F.; Schlick, E. [Knoll, S.a., Madrid (Spain)

    1994-12-31

    Using the structural similarity between 8-flavoneacetic acid the antitumor quinolones, we have prepared some hybrid compounds on both systems and studied their cytotoxicity. None of the sinthesized compounds have shown sufficient interest for further development. 33 refs.

  11. Potency trends of Δ9-THC and other cannabinoids in confiscated cannabis preparations from 1993 to 2008.

    Science.gov (United States)

    Mehmedic, Zlatko; Chandra, Suman; Slade, Desmond; Denham, Heather; Foster, Susan; Patel, Amit S; Ross, Samir A; Khan, Ikhlas A; ElSohly, Mahmoud A

    2010-09-01

    The University of Mississippi has a contract with the National Institute on Drug Abuse (NIDA) to carry out a variety of research activities dealing with cannabis, including the Potency Monitoring (PM) program, which provides analytical potency data on cannabis preparations confiscated in the United States. This report provides data on 46,211 samples seized and analyzed by gas chromatography-flame ionization detection (GC-FID) during 1993-2008. The data showed an upward trend in the mean Δ(9)-tetrahydrocannabinol (Δ(9)-THC) content of all confiscated cannabis preparations, which increased from 3.4% in 1993 to 8.8% in 2008. Hashish potencies did not increase consistently during this period; however, the mean yearly potency varied from 2.5-9.2% (1993-2003) to 12.0-29.3% (2004-2008). Hash oil potencies also varied considerably during this period (16.8 ± 16.3%). The increase in cannabis preparation potency is mainly due to the increase in the potency of nondomestic versus domestic samples.

  12. A Semi-quantitative Serological Method to Assess the Potency of Inactivated Rabies Vaccine for Veterinary Use

    Institute of Scientific and Technical Information of China (English)

    Ye Liu; Shoufeng Zhang; Fei Zhang; Rongliang Hu

    2012-01-01

    Potency is one of the most important indexes of inactivated vaccines.A number of methods have been established to assay the potency,of which the NIH test and single-dose mouse protection test are the "prescribed methods".Here,we report a method to semi-quantitatively assay the potency of an inactivated rabies vaccine,which uses fewer animals and takes less time to complete.Depending on the quality requirements of a vaccine(e.g.minimum potency),a rabies reference vaccine is,for example,diluted to the minimum potency,and 50 μL of the dilution is taken to inoculate 10 mice.The same amount of the test rabies vaccine is inoculated into another 10 mice.After two weeks,all mice are bled and serum samples are assayed for viral neutralizing antibody by the fluorescent antibody virus neutralization(FAVN) test.By comparing the median and interquartile range of antibody titers of the reference vaccine with those of the test vaccine,the test vaccine potency can be semi-quantitatively judged as to whether it is in accord with the required quality.The reliability of this method was also confirmed in dogs.The procedure can be recommended for batch potency testing during inactivated rabies vaccine production.

  13. Estimating Potency in High-Throughput Screening Experiments by Maximizing the Rate of Change in Weighted Shannon Entropy.

    Science.gov (United States)

    Shockley, Keith R

    2016-06-15

    High-throughput in vitro screening experiments can be used to generate concentration-response data for large chemical libraries. It is often desirable to estimate the concentration needed to achieve a particular effect, or potency, for each chemical tested in an assay. Potency estimates can be used to directly compare chemical profiles and prioritize compounds for confirmation studies, or employed as input data for prediction modeling and association mapping. The concentration for half-maximal activity derived from the Hill equation model (i.e., AC50) is the most common potency measure applied in pharmacological research and toxicity testing. However, the AC50 parameter is subject to large uncertainty for many concentration-response relationships. In this study we introduce a new measure of potency based on a weighted Shannon entropy measure termed the weighted entropy score (WES). Our potency estimator (Point of Departure, PODWES) is defined as the concentration producing the maximum rate of change in weighted entropy along a concentration-response profile. This approach provides a new tool for potency estimation that does not depend on the assumption of monotonicity or any other pre-specified concentration-response relationship. PODWES estimates potency with greater precision and less bias compared to the conventional AC50 assessed across a range of simulated conditions.

  14. Sanctioning Large-Scale Domestic Cannabis Production - Potency, Yield and Professionalism

    DEFF Research Database (Denmark)

    Møller, Kim; Lindholst, Christian

    2014-01-01

    Domestically cultivated cannabis, referred to as sinsemilla, constitutes a growing share of the illicit drug markets in the Scandinavian countries. In this study we present forensic evidence of THC content in sinsemilla and resin confiscated by the Danish police from 2008 to 2012. The purpose...... is to establish a mean potency, a yield estimate for professionally grown plants, and an assessment of how „professionalism” applies to domestic cultivation. We find a mean THC content in our sample normally distributed around 12% for sinsemilla (n=35) and 11.7% for resin (n=99). This is markedly higher than...... the assumption of THC content in sinsemilla between 6-8% as is currently applied in Norway and Sweden. It is also higher than the previous estimate of resin potency. The yield in sinsemilla plants is found to be 46 grams per plant. This is much lower than the estimate applied in criminal cases, which indicates...

  15. Evaluation of monoquaternary pyridinium oximes potency to reactivate tabun-inhibited human acetylcholinesterase.

    Science.gov (United States)

    Odzak, Renata; Calić, Maja; Hrenar, Tomica; Primozic, Ines; Kovarik, Zrinka

    2007-04-20

    Monoquaternary N-benzyl-4-hydroxyiminomethylpyridinium bromide (Py-4-H) and its analogous with diverse substituents introduced into the phenyl ring (Py-4-CH(3), Py-4-Br, Py-4-Cl and Py-4-NO(2)) were synthesized in order to examine their potency as reactivators of tabun-inhibited human erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7). Within 24h, the reactivation of tabun-inhibited AChE reached 80% with Py-4-CH(3), Py-4-Br and Py-4-Cl, 40% with Py-4-NO(2), and 30% with Py-4-H. The overall reactivation rate constants were up to 5.0min(-1)M(-1). All oximes inhibited human AChE reversibly, and the inhibition potency increased in the following order Py-4-Brtabun-phosphorylated human AChE.

  16. Phospholipase Czeta mRNA expression and its potency during spermatogenesis for activation of quail oocyte as a sperm factor.

    Science.gov (United States)

    Mizushima, Shusei; Takagi, Soichi; Ono, Tamao; Atsumi, Yusuke; Tsukada, Akira; Saito, Noboru; Shimada, Kiyoshi

    2009-12-01

    This study was conducted to investigate the role of a sperm-borne compound in oocyte activation in special reference to the time when oocyte activation is required by testicular cells during spermatogenesis in quail. First, effects of a microinjection of quail sperm extract (SE) and quail phospholipase Czeta (PLCzeta) cRNA into quail oocytes were assessed by observation of pronuclear formation and cytoplasmic segmentation, respectively. Secondly, the effects of a microinjection of round spermatids with or without PLCzeta cRNA into quail oocytes were studied by observation of development. When the oocytes were injected with SE at 0.13 mg protein/ml, both pronuclear formation and cytoplasmic segmentation were optimally induced. However, pronuclear formation was blocked when SE was pretreated with heat or when the oocyte was pretreated with BAPTA (a Ca(2+) chelator) before SE injection. On the other hand, when the oocytes were injected with PLCzeta cRNA at 60 microg/ml, not only pronuclear formation but also cytoplasmic segmentation were optimally induced. However, PLCzeta cRNA-induced pronuclear formation was blocked by pretreatment with cycloheximide (an inhibitor of protein synthesis) or with BAPTA. Most interestingly, round spermatids alone cannot induce blastodermal development but microinjection of a round spermatid with PLCzeta cRNA can induce development. In addition, RT-PCR revealed that PLCzeta mRNA is expressed in elongated spermatids and testicular sperm but not in round spermatids. It is concluded that PLCzeta is a functional sperm factor for oocyte activation to initiate resumption of meiotic division in quail and its potency is acquired after elongated spermatid formation during the spermatogenesis.

  17. Utilization of Quinolones in Our Hospital from 2009 to 2011%2009~2011年喹诺酮类药物应用分析

    Institute of Scientific and Technical Information of China (English)

    徐春燕

    2013-01-01

      目的探讨我院喹诺酮类药物的应用现状及趋势。方法采用限定日剂量方法,对我院2009~2011年喹诺酮类药物的应用品种、销售金额、用药频度(DDDs)和日均费用(DDC)进行统计、分析。结果3年来,在口服喹诺酮类药物中,销售金额处于前三位的是加替沙星胶囊、左氧氟沙星胶囊、氟罗沙星胶囊;在注射喹诺酮类药物中,销售金额和DDDs排序列前四位的有盐酸左氧氟沙星注射液、加替沙星针、氟罗沙星针、依诺沙星注射液。结论我院喹诺酮类药物应用基本合理,但仍应进一步加强其使用监督管理。%Objective To evaluate the utilization and tendency of quinolones in our hospital. Methods Using DDD meth-od, the utilization of quinolones in our hospital from 2009 to 2011 were analyzed statistical y in terms of drug variety, consump-tion sum, DDDs and DDC, etc. Results The percentages of the consumption sum of quinolone in antibiotic drugs decreased year by year. Over the 3 years, the first 3 quinolones oral agents in the list of consumption sum and DDDs were Gatifloxacin capsules, Levofloxacin capsules and Fleroxacin capsules.The first 4 quinolones for injection in the list of consumption sum and DDDs included Levofloxacin injection, Gatifloxacin injection, Fleroxacin injection, Enoxacin injection. Conclusion The application of quinolone in our hospital is reasonable but should be strengthened in respect of the management of drug use.

  18. Utilization of Quinolones in Our Hospital from 2007 to 2009%我院2007-2009年喹诺酮类药应用分析

    Institute of Scientific and Technical Information of China (English)

    张桂芬; 支伟锋; 归莱; 谢丹

    2011-01-01

    OBJECTIVE: To evaluate the utilization and tendency of quinolones in our hospital. METHODS: Using DDD method, the utilization of quinolones in our hospital from 2007 to 2009 were analyzed statistically in terms of drug variety, consumption sum, DDDs and DDC, etc. RESULTS: The percentages of the consumption sum of quinolone in antibiotic drugs decreased year by year. Over the 3 years, the first 3 quinolones oral agents in the list of consumption sum and DDDs were Lomefloxacin tablets,Gatifloxacin capsules and Levofloxacin tablets (domestic). The first 4 quinolones for injection in the list of consumption sum and DDDs included Levofloxacin injection(domestic), Ciprofloxacin sodium chloride injection, Fleroxacin glucose injection. CONCLUSION: The application of quinolone in our hospital is reasonable but should be strengthened in respect of the management of drug use.%目的:评价我院喹诺酮类药的应用现状及趋势.方法:采用限定日剂量方法,对我院2007-2009年喹诺酮类药的应用品种、销售金额、用药频度(DDDs)和日均费用(DDC)进行统计、分析.结果:喹诺酮类药销售金额在抗菌药物中所占比例逐年下降.3年来,在口服喹诺酮类药中,销售金额、DDDs排序列前3位的依次是洛美沙星片、加替沙星胶囊、左氧氟沙星片(国产);在注射喹诺酮类药中,销售金额、DDDs排序列前4位的均有左氧氟沙星注射液(国产)、环丙沙星氯化钠注射液、氟罗沙星葡萄糖注射液.结论:我院喹诺酮类药应用基本合理,但仍应进一步加强其使用监管.

  19. Substitutions of Ser83Leu in GyrA and Ser80Leu in ParC Associated with Quinolone Resistance in Acinetobacter pittii.

    Science.gov (United States)

    Gu, Dan-xia; Hu, Yun-jian; Zhou, Hong-wei; Zhang, Rong; Chen, Gong-xiang

    2015-06-01

    To investigate the prevalence and the mechanism of quinolone-resistant Acinetobacter pittii, 634 Acinetobacter calcoaceticus-Acinetobacter baumannii complex isolates were collected throughout Zhejiang Province. Identification of isolates was conducted by matrix-assisted laser desorption ionization/time of flight mass spectrometry (MALDI-TOF MS), blaOXA-51-like gene, and partial RNA polymerase β-subunit (rpoB) amplification. Twenty-seven isolates of A. pittii were identified. Among the 634 isolates, A. baumannii, A. pittii, Acinetobacter nosocomialis, and A. calcoaceticus counted for 87.22%, 4.26%, 8.20%, and 0.32%, respectively. Antimicrobial susceptibility of nalidixic acid, ofloxacin, enoxacin, ciprofloxacin, lomefloxacin, levofloxacin, sparfloxacin, moxifloxacin, and gatifloxacin for 27 A. pittii were determined by the agar dilution method. Detection of quinolone-resistant determining regions of gyrA, gyrB, parC, and parE was performed for the A. pittii isolates. In addition, plasmid-mediated quinolone resistance (PMQR) determinants (qnrA, qnrB, qnrS, qnrC, qnrD, aac(6')-Ib-cr, qepA, oqxA, and oqxB) were investigated. All the 27 isolates demonstrated a higher minimum inhibitory concentration (MIC) to old quinolones than the new fluoroquinolones. No mutation in gyrA, gyrB, parC, or parE was detected in 20 ciprofloxacin-susceptible isolates. Seven ciprofloxacin-resistant A. pittii were identified with a Ser83Leu mutation in GyrA. Among them, six isolates with simultaneous Ser83Leu amino acid substitution in GyrA and Ser80Leu in ParC displayed higher MIC values against ciprofloxacin. Additionally, three were identified with a Met370Ile substitution in ParE, and two were detected with a Tyr317His mutation in ParE, which were reported for the first time. No PMQR determinants were identified in the 27 A. pittii isolates. In conclusion, mutations in chromosome play a major role in quinolone resistance in A. pittii, while resistance mechanisms mediated by plasmid have

  20. [Prevalence of quinolone resistance mechanisms in Enterobacteriaceae producing acquired AmpC β-lactamases and/or carbapenemases in Spain].

    Science.gov (United States)

    Machuca, Jesús; Agüero, Jesús; Miró, Elisenda; Conejo, María Del Carmen; Oteo, Jesús; Bou, Germán; González-López, Juan José; Oliver, Antonio; Navarro, Ferran; Pascual, Álvaro; Martínez-Martínez, Luis

    2016-06-23

    Quinolone resistance in Enterobacteriaceae species has increased over the past few years, and is significantly associated to beta-lactam resistance. The aim of this study was to evaluate the prevalence of chromosomal- and plasmid-mediated quinolone resistance in acquired AmpC β-lactamase and/or carbapenemase-producing Enterobacteriaceae isolates. The presence of chromosomal- and plasmid-mediated quinolone resistance mechanisms [mutations in the quinolone resistance determining region (QRDR) of gyrA and parC and qnr, aac(6')-Ib-cr and qepA genes] was evaluated in 289 isolates of acquired AmpC β-lactamase- and/or carbapenemase-producing Enterobacteriaceae collected between February and July 2009 in 35 Spanish hospitals. Plasmid mediated quinolone resistance (PMQR) genes were detected in 92 isolates (31.8%), qnr genes were detected in 83 isolates (28.7%), and the aac(6')-Ib-cr gene was detected in 20 isolates (7%). qnrB4 gene was the most prevalent qnr gene detected (20%), associated, in most cases, with DHA-1. Only 14.6% of isolates showed no mutations in gyrA or parC with a ciprofloxacin MIC of 0.5mg/L or higher, whereas PMQR genes were detected in 90% of such isolates. qnrB4 gene was the most prevalent PMQR gene detected, and was significantly associated with acquired AmpC β-lactamase DHA-1. PMQR determinants in association with other chromosomal-mediated quinolone resistance mechanisms, different to mutations in gyrA and parC (increased energy-dependent efflux, altered lipopolysaccharide or porin loss), could lead to ciprofloxacin MIC values that exceed breakpoints established by the main international committees to define clinical antimicrobial susceptibility breakpoints. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.