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Sample records for vivo fluoroquinolone concentrations

  1. Fluoroquinolone's effect on growth of human chondrocytes and chondrosarcomas. In vitro and in vivo correlation

    DEFF Research Database (Denmark)

    Multhaupt, H A; Alvarez, J C; Rafferty, P A

    2001-01-01

    Clinical and in vitro studies have demonstrated that fluoroquinolones are toxic to chondrocytes; however, the exact mechanism of fluoroquinolone arthropathy is unknown. We investigated the toxicity of ciprofloxacin on normal cartilage and on cartilaginous tumors. Normal human cartilage, enchondroma...... with use of conventional light microscopy, electron microscopy, and immunohistochemistry to identify extracellular matrix, cell proliferation, and apoptosis. Cultures of normal chondrocytes expressed type-II collagen. Electron microscopy revealed a large amount of glycogen in the cells; the presence of fat...... of vimentin filaments. The treated chondrocytes showed a decrease in cell proliferation, but there was no induction of apoptosis or effect on the expression of extracellular matrix proteins. Ciprofloxacin-treated chondrosarcoma cultures and tissue samples showed changes in cartilage matrix composition...

  2. In vitro and in vivo antibacterial activities of DK-507k, a novel fluoroquinolone.

    Science.gov (United States)

    Otani, Tsuyoshi; Tanaka, Mayumi; Ito, Emi; Kurosaka, Yuichi; Murakami, Yoichi; Onodera, Kiyomi; Akasaka, Takaaki; Sato, Kenichi

    2003-12-01

    The antibacterial activities of DK-507k, a novel quinolone, were compared with those of other quinolones: ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sitafloxacin, and garenoxacin (BMS284756). DK-507k was as active as sitafloxacin and was as active as or up to eightfold more active than gatifloxacin, moxifloxacin, and garenoxacin against Streptococcus pneumoniae, methicillin-susceptible and methicillin-resistant Staphylococcus aureus, and coagulase-negative staphylococci. DK-507k was as active as or 4-fold more active than garenoxacin and 2- to 16-fold more active than gatifloxacin and moxifloxacin against ciprofloxacin-resistant strains of S. pneumoniae, including clinical isolates and in vitro-selected mutants with known mutations. DK-507k inhibited all ciprofloxacin-resistant strains of S. pneumoniae at 1 microg/ml. A time-kill assay with S. pneumoniae showed that DK-507k was more bactericidal than gatifloxacin and moxifloxacin. The activities of DK-507k against most members of the family Enterobacteriaceae were comparable to those of ciprofloxacin and equal to or up to 32-fold higher than those of gatifloxacin, levofloxacin, moxifloxacin, and garenoxacin. DK-507k was fourfold less active than sitafloxacin and ciprofloxacin against Pseudomonas aeruginosa, while it was two to four times more potent than levofloxacin, gatifloxacin, moxifloxacin, and garenoxacin against P. aeruginosa. In vivo, intravenous treatment with DK-507k was more effective than that with gatifloxacin and moxifloxacin against systemic infections caused by S. aureus, S. pneumoniae, and P. aeruginosa in mice. In a mouse model of pneumonia due to penicillin-resistant S. pneumoniae, DK-507k administered subcutaneously showed dose-dependent efficacy and eliminated the bacteria from the lungs, whereas gatifloxacin and moxifloxacin had no significant efficacy. Oral treatment with DK-507k was slightly more effective than that with ciprofloxacin in a rat model of foreign body

  3. Impact of Fluoroquinolone Resistance Mutations on Gonococcal Fitness and In Vivo Selection for Compensatory Mutations

    Science.gov (United States)

    Kunz, Anjali N.; Begum, Afrin A.; Wu, Hong; D'Ambrozio, Jonathan A.; Robinson, James M.; Shafer, William M.; Bash, Margaret C.; Jerse, Ann E.

    2012-01-01

    Background. Quinolone-resistant Neisseria gonorrhoeae (QRNG) arise from mutations in gyrA (intermediate resistance) or gyrA and parC (resistance). Here we tested the consequence of commonly isolated gyrA91/95 and parC86 mutations on gonococcal fitness. Methods. Mutant gyrA91/95 and parC86 alleles were introduced into wild-type gonococci or an isogenic mutant that is resistant to macrolides due to an mtrR−79 mutation. Wild-type and mutant bacteria were compared for growth in vitro and in competitive murine infection. Results. In vitro growth was reduced with increasing numbers of mutations. Interestingly, the gyrA91/95 mutation conferred an in vivo fitness benefit to wild-type and mtrR−79 mutant gonococci. The gyrA91/95, parC86 mutant, in contrast, showed a slight fitness defect in vivo, and the gyrA91/95, parC86, mtrR−79 mutant was markedly less fit relative to the parent strains. A ciprofloxacin-resistant (CipR) mutant was selected during infection with the gyrA91/95, parC86, mtrR−79 mutant in which the mtrR−79 mutation was repaired and the gyrA91 mutation was altered. This in vivo–selected mutant grew as well as the wild-type strain in vitro. Conclusions. gyrA91/95 mutations may contribute to the spread of QRNG. Further acquisition of a parC86 mutation abrogates this fitness advantage; however, compensatory mutations can occur that restore in vivo fitness and maintain CipR. PMID:22492860

  4. Wild-type MIC distributions of four fluoroquinolones active against Mycobacterium tuberculosis in relation to current critical concentrations and available pharmacokinetic and pharmacodynamic data.

    Science.gov (United States)

    Angeby, K A; Jureen, P; Giske, C G; Chryssanthou, E; Sturegård, E; Nordvall, M; Johansson, A G; Werngren, J; Kahlmeter, G; Hoffner, S E; Schön, T

    2010-05-01

    To describe wild-type distributions of the MIC of fluoroquinolones for Mycobacterium tuberculosis in relation to current critical concentrations used for drug susceptibility testing and pharmacokinetic/pharmacodynamic (PK/PD) data. A 96-stick replicator on Middlebrook 7H10 medium was used to define the MICs of ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin for 90 consecutive clinical strains and 24 drug-resistant strains. The MICs were compared with routine BACTEC 460 susceptibility results and with MIC determinations in the BACTEC MGIT 960 system in a subset of strains using ofloxacin as a class representative. PK/PD data for each drug were reviewed in relation to the wild-type MIC distribution. The wild-type MICs of ciprofloxacin, ofloxacin, moxifloxacin and levofloxacin were distributed from 0.125 to 1, 0.25 to 1, 0.032 to 0.5 and 0.125 to 0.5 mg/L, respectively. The MIC data correlated well with the BACTEC 960 MGIT and BACTEC 460 results. PD indices were the most favourable for levofloxacin, followed by moxifloxacin, ofloxacin and ciprofloxacin. We propose S (susceptible) concentrations of S

  5. Fluoroquinolone treatment and susceptibility of isolates from bacterial keratitis.

    Science.gov (United States)

    Ray, Kathryn J; Prajna, Lalitha; Srinivasan, Muthiah; Geetha, Manoharan; Karpagam, Rajarathinam; Glidden, David; Oldenburg, Catherine E; Sun, Catherine Q; McLeod, Stephen D; Acharya, Nisha R; Lietman, Thomas M

    2013-03-01

    To analyze the relationship between fluoroquinolone use at presentation and minimum inhibitory concentration in bacterial keratitis. The Steroids for Corneal Ulcers Trial was a randomized, double-masked, placebo-controlled trial assessing the effect of adjunctive topical corticosteroid treatment on outcomes in bacterial keratitis. After presentation, all patients were treated with moxifloxacin hydrochloride, 0.5%. We compare antibiotic use at presentation with minimum inhibitory concentration against moxifloxacin for all isolates. Separate analyses accounted for organism species and fluoroquinolone generation. Topical fluoroquinolone use at presentation was reported in 92 of 480 cases (19.2%). Causative organisms in the 480 cases included Streptococcus pneumoniae (247 cases [51.5%]), Pseudomonas aeruginosa (109 cases [22.7%]), and Nocardia species (55 cases [11.5%]). Isolates from patients who reported fluoroquinolone use at presentation had a 2.01-fold-higher minimum inhibitory concentration (95% CI, 1.39-fold to 2.91-fold; P < .001). Fourth-generation fluoroquinolones were associated with a 3.48-fold-higher minimum inhibitory concentration than those isolates that were not exposed to pretreatment at enrollment (95% CI, 1.99-fold to 6.06-fold; P < .001). This study provides evidence that prior use of fluoroquinolones is associated with antibiotic resistance. clinicaltrials.gov Identifier: NCT00324168.

  6. The use of systemic fluoroquinolones.

    Science.gov (United States)

    2006-09-01

    The only indications for which a fluoroquinolone (ie, ciprofloxacin) is licensed by the US Food and Drug Administration for use in patients younger than 18 years are complicated urinary tract infections, pyelonephritis, and postexposure treatment for inhalation anthrax. Nonetheless, approximately 520,000 prescriptions for fluoroquinolones were written in the United States for patients younger than 18 years in 2002; 13,800 were written for infants and children 2 to 6 years of age, and 2750 were written for infants younger than 2 years. Clinical trials of fluoroquinolones in pediatric patients with various diagnoses have been published and are reviewed. Fluoroquinolones cause arthrotoxicity in juvenile animals and have been associated with reversible musculoskeletal events in both children and adults. Other adverse events associated with fluoroquinolones include central nervous system disorders, photosensitivity, disorders of glucose homeostasis, prolongation of QT interval with rare cases of torsade de pointes (often lethal ventricular arrhythmia in patients with long QT syndrome), hepatic dysfunction, and rashes. The increased use of fluoroquinolones in adults has resulted in increased bacterial resistance to this class of antibacterial agents. This report provides specific guidelines for the systemic use of fluoroquinolones in children. Fluoroquinolone use should be restricted to situations in which there is no safe and effective alternative to treat an infection caused by multidrug-resistant bacteria or to provide oral therapy when parenteral therapy is not feasible and no other effective oral agent is available.

  7. Safety of Fluoroquinolones: An Update

    Directory of Open Access Journals (Sweden)

    L Mandell

    2002-01-01

    Full Text Available The fluoroquinolone class of antimicrobials has been in clinical use for over 13 years. During that period, some representatives of the class have been extensively prescribed, such as ciprofloxacin and levofloxacin, while others have seen minimal use and have been restricted or withdrawn, namely, trovafloxacin and grepafloxacin. Manipulation of the fluoroquinolone structure by substituting a range of moieties around the core has yielded enhanced antibacterial activity, but in some cases this has come at a price. Specific substitutions are discussed in relation to particular recognized adverse events. In the present paper, newly introduced fluoroquinolones, such as moxifloxacin and gatifloxacin, are examined in terms of anticipated class effects and recent clinical experience. These antimicrobials are associated with reactions such as diarrhea, nausea, headache and other typical antimicrobial phenomena at rates less than 5%. New fluoroquinolone agents should be examined carefully in light of structural findings until adequate clinical data are amassed.

  8. SOS response and its regulation on the fluoroquinolone resistance.

    Science.gov (United States)

    Qin, Ting-Ting; Kang, Hai-Quan; Ma, Ping; Li, Peng-Peng; Huang, Lin-Yan; Gu, Bing

    2015-12-01

    Bacteria can survive fluoroquinolone antibiotics (FQs) treatment by becoming resistant through a genetic change-mutation or gene acquisition. The SOS response is widespread among bacteria and exhibits considerable variation in its composition and regulation, which is repressed by LexA protein and derepressed by RecA protein. Here, we take a comprehensive review of the SOS gene network and its regulation on the fluoroquinolone resistance. As a unique survival mechanism, SOS may be an important factor influencing the outcome of antibiotic therapy in vivo.

  9. Fluorescence quenching of fluoroquinolones by gold nanoparticles with different sizes and its analytical application

    Energy Technology Data Exchange (ETDEWEB)

    Amjadi, Mohammad, E-mail: amjadi@tabrizu.ac.ir; Farzampour, Leila

    2014-01-15

    The interaction of some fluoroquinolones including norfloxacin, ciprofloxacin, danofloxacin and ofloxacin with gold nanoparticles (AuNPs) of different sizes (8, 20 and 75 nm) was studied. In the studied systems, fluoroquinolones are noncovalently adsorbed onto the surface of AuNPs, which results in severe quenching of fluoroquinolones fluorescence possibly as a result of fluorescence resonance energy transfer. Stern–Volmer quenching constants were obtained and found to increase with an increase in the size of AuNPs. Moreover, the interactions between some thiols and fluoroquinolone-adsorbed AuNPs were investigated to explore the analytical applicability of the systems. It was found that upon the addition of thiols to fluoroquinolone-AuNPs systems the fluorescence of fluoroquinolones switches to “turn-on” due to the strong binding of thiols to AuNPs and removal of quinolines from NP surface. Under the optimum conditions, the fluorescence enhancement showed a linear relationship with the concentration of thiols, indicating the analytical usefulness of the system. -- Highlights: • Interaction of fluoroquinolones with AuNPs of different sizes was investigated. • The fluorescence of fluoroquinolones is efficiently quenched by AuNPs. • The fluorescence quenching efficiency increases by increasing NP size. • Fluoroquinolone-AuNPs systems can be used as sensitive turn-on sensors for thiols. • Danofloxacin-20-nm AuNPs system exhibits the highest sensitivity for thiols.

  10. In vitro study of the interaction between some fluoroquinolones and ...

    African Journals Online (AJOL)

    The cup diffusion method (CD) was used to evaluate the in vitro interaction of some fluoroquinolones (ciprofloxacin, pefloxacin and levofloxacin) with extracts of Kola nitida seed (KNS) against a clinical isolate of Escherichia coli. Minimum inhibitory concentration (MIC) of the drugs was determined separately and in ...

  11. Systemic use of fluoroquinolone in children

    Directory of Open Access Journals (Sweden)

    Soo-Han Choi

    2013-05-01

    Full Text Available Fluoroquinolones are an important class of antibiotics that are widely used in adult patients because of their broad spectrum of activity, good tissue penetration, and oral bioavailability. However, fluoroquinolone use in children is limited because juvenile animals developed arthropathy in previous experiments on fluoroquinolone use. Indications for fluoroquinolone use in patients younger than 18 years, as stated by the U.S. Food and Drug Administration, include treatment of complicated urinary tract infections and postexposure treatment for inhalation anthrax. In Korea, the systemic use of fluoroquinolones has not been approved in children younger than 18 years. Although concerns remain regarding the adverse musculoskeletal effects of fluoroquinolones in children, their use in the pediatric population has increased in many circumstances. While pediatricians should be aware of the indications and adverse effects of fluoroquinolones, recent studies have shown that the risk for musculoskeletal complications in children did not significantly increase following fluoroquinolone treatment. In addition, fluoroquinolones may be particularly helpful in treating multidrug-resistant infections that have not responded to standard antibiotic therapy in immunocompromised patients. In the present article, we provide an updated review on the safety and current recommendations for using fluoroquinolones in children.

  12. Comparison of the in vitro activities of several new fluoroquinolones against respiratory pathogens and their abilities to select fluoroquinolone resistance.

    Science.gov (United States)

    Boswell, F J; Andrews, J M; Jevons, G; Wise, R

    2002-10-01

    In this study the in vitro activities and pharmacodynamic properties of moxifloxacin, levofloxacin, gatifloxacin and gemifloxacin were compared on recently isolated respiratory pathogens and strains of Streptococcus pneumoniae with known mechanisms of fluoroquinolone resistance. In addition, the resistance selection frequencies of moxifloxacin and levofloxacin on three recently isolated respiratory pathogens and four strains of S. pneumoniae with known mechanisms of fluoroquinolone resistance were investigated. The four fluoroquinolones had similar activities against both Moraxella catarrhalis (MIC(90)s 0.015-0.06 mg/L) and Haemophilus influenzae (MIC(90)s 0.008-0.03 mg/L). More marked differences in activity were noted with S. pneumoniae, with MIC(90)s of 0.25, 1, 0.5 and 0.03 mg/L for moxifloxacin, levofloxacin, gatifloxacin and gemifloxacin, respectively. With the S. pneumoniae strains, the four fluoroquinolones exhibited similar concentration-dependent time-kill kinetics. The resistance selection frequencies of levofloxacin were higher than those of moxifloxacin at concentrations equivalent to those at the end of the dosing interval. Therefore moxifloxacin may have less of an impact on the development of resistance than levofloxacin.

  13. Removal of five fluoroquinolone antibiotics during broiler manure composting.

    Science.gov (United States)

    Yang, Bing; Meng, Lei; Xue, Nandong

    2018-02-01

    Composting is a cost-effective approach for the removal of antibiotics from the environment; however, the consequence of this approach on fluoroquinolone antibiotics is limited. The fate of five representative fluoroquinolone antibiotics, namely ciprofloxacin, enrofloxacin, lomefloxacin, norfloxacin, and sarafloxacin, was investigated in a pilot-scale composting of broiler manure over 42 days. The effect of antibiotic concentrations (at a dose of 15, 30, or 60 mg/kg for each and a control without antibiotic addition) on the composting process was also assessed. The 42-day composting showed 45.3-75.4% of antibiotic removal with species-specific patterns. However, the observed variations in such removal among both antibiotics concentrations and composting times were not significant in most cases, possibly indicating a slight side-effect of the tested antibiotic concentrations on the composting process. To the best of our knowledge, this study is among few studies with a focus on the persistence of fluoroquinolone antibiotics during a pilot-scale composting, which warrants further study in regards to the mechanism underlying the removal of these compounds during composting.

  14. Comparative study of the in vitro activity of a new fluoroquinolone, ABT-492.

    Science.gov (United States)

    Harnett, S J; Fraise, A P; Andrews, J M; Jevons, G; Brenwald, N P; Wise, R

    2004-05-01

    The in vitro activity of a new fluoroquinolone, ABT-492, was determined. MICs were compared with those of two beta-lactams, telithromycin, ciprofloxacin and four later generation fluoroquinolones. The effects of human serum and of inoculum concentration were also investigated. MIC data indicate that ABT-492 has potent activity against Gram-positive organisms with enhanced anti-staphylococcal activity compared with earlier fluoroquinolones, in addition to activity against beta-haemolytic streptococci, pneumococci including penicillin- and fluoroquinolone-resistant strains and vancomycin-susceptible and -resistant Enterococcus faecalis but not Enterococcus faecium. ABT-492 was the most active agent tested against Haemophilus influenzae, Moraxella catarrhalis, Neisseria meningitidis, fluoroquinolone-susceptible Neisseria gonorrhoeae and anaerobes. Good activity was observed for ABT-492 amongst the Enterobacteriaceae and anaerobes tested, but ciprofloxacin showed superior activity for species of Proteus, Morganella and Providencia, as well as for Pseudomonas spp. In common with the other fluoroquinolones tested, organisms with reduced susceptibility to ciprofloxacin had raised MIC(90)s to ABT-492. The one isolate of H. influenzae tested with reduced fluoroquinolone susceptibility had an ABT-492 MIC close to that of the population lacking a mechanism of quinolone resistance. ABT-492 was more active than ciprofloxacin against Chlamydia spp. An inoculum effect was observed with a number of isolates of Staphylococcus aureus, Streptococcus pneumoniae, E. faecium, Klebsiella spp. and Escherichia coli, in addition to moderately raised MICs in the presence of 70% serum protein. The clinical significance of these findings is yet to be determined. ABT-492 is a new fluoroquinolone with excellent activity against both Gram-positive and Gram-negative organisms, with many potential clinical uses.

  15. Detection of a wide variety of human and veterinary fluoroquinolone antibiotics in municipal wastewater and wastewater-impacted surface water.

    Science.gov (United States)

    He, Ke; Soares, Ana Dulce; Adejumo, Hollie; McDiarmid, Melissa; Squibb, Katherine; Blaney, Lee

    2015-03-15

    As annual sales of antibiotics continue to rise, the mass of these specially-designed compounds entering municipal wastewater treatment systems has also increased. Of primary concern here is that antibiotics can inhibit growth of specific microorganisms in biological processes of wastewater treatment plants (WWTPs) or in downstream ecosystems. Growth inhibition studies with Escherichia coli demonstrated that solutions containing 1-10 μg/L of fluoroquinolones can inhibit microbial growth. Wastewater samples were collected on a monthly basis from various treatment stages of a 30 million gallon per day WWTP in Maryland, USA. Samples were analyzed for the presence of 11 fluoroquinolone antibiotics. At least one fluoroquinolone was detected in every sample. Ofloxacin and ciprofloxacin exhibited detection frequencies of 100% and 98%, respectively, across all sampling sites. Concentrations of fluoroquinolones in raw wastewater were as high as 1900 ng/L for ciprofloxacin and 600 ng/L for ofloxacin. Difloxacin, enrofloxacin, fleroxacin, moxifloxacin, norfloxacin, and orbifloxacin were also detected at appreciable concentrations of 9-170 ng/L. The total mass concentration of fluoroquinolones in raw wastewater was in the range that inhibited E. coli growth, suggesting that concerns over antibiotic presence in wastewater and wastewater-impacted surface water are valid. The average removal efficiency of fluoroquinolones during wastewater treatment was approximately 65%; furthermore, the removal efficiency for fluoroquinolones was found to be negatively correlated to biochemical oxygen demand removal and positively correlated to phosphorus removal. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Deoxynybomycins inhibit mutant DNA gyrase and rescue mice infected with fluoroquinolone-resistant bacteria.

    Science.gov (United States)

    Parkinson, Elizabeth I; Bair, Joseph S; Nakamura, Bradley A; Lee, Hyang Y; Kuttab, Hani I; Southgate, Emma H; Lezmi, Stéphane; Lau, Gee W; Hergenrother, Paul J

    2015-04-24

    Fluoroquinolones are one of the most commonly prescribed classes of antibiotics, but fluoroquinolone resistance (FQR) is widespread and increasing. Deoxynybomycin (DNM) is a natural-product antibiotic with an unusual mechanism of action, inhibiting the mutant DNA gyrase that confers FQR. Unfortunately, isolation of DNM is difficult and DNM is insoluble in aqueous solutions, making it a poor candidate for development. Here we describe a facile chemical route to produce DNM and its derivatives. These compounds possess excellent activity against FQR methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci clinical isolates and inhibit mutant DNA gyrase in-vitro. Bacteria that develop resistance to DNM are re-sensitized to fluoroquinolones, suggesting that resistance that emerges to DNM would be treatable. Using a DNM derivative, the first in-vivo efficacy of the nybomycin class is demonstrated in a mouse infection model. Overall, the data presented suggest the promise of DNM derivatives for the treatment of FQR infections.

  17. Drug susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones

    DEFF Research Database (Denmark)

    Johansen, I S; Larsen, A R; Sandven, P

    2003-01-01

    In the first attempt to establish a quality assurance programme for susceptibility testing of Mycobacterium tuberculosis to fluoroquinolones, 20 strains with different fluoroquinolone susceptibility patterns were distributed by the Supranational Reference Laboratory in Stockholm to the other...

  18. Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India.

    Science.gov (United States)

    Banerjee, Tuhina; Anupurba, Shampa

    2016-10-01

    Fluoroquinolone resistance in both Gram-positive and Gram-negative bacteria has increased with the widespread use of fluoroquinolones. Fluoroquinolone resistance in Gram-negative bacilli has been widely studied, though staphylococci and enterococci are also notably resistant. Enterococci being the second most common cause of healthcare-associated urinary tract infections (UTIs) fluoroquinolones are often the drug of choice. This study was undertaken to assess the risk factors associated with fluoroquinolone-resistant enterococcal UTI in a tertiary level health facility in north India. A total of 365 patients with UTI caused by enterococci were studied over a period of two years. Patients with ciprofloxacin-resistant and susceptible UTI were considered as cases and controls, respectively. Resistance profile of the isolates against common antibiotics was studied by minimum inhibitory concentration (MIC) determination. Mechanisms for fluoroquinolone resistance was studied by efflux pump inhibitor activity and multiplex PCR targeting the qnr genes. A total of 204 (55.89%) cases and 161 (44.1%) controls were identified. The fluoroquinolone-resistant isolates were significantly resistant to ampicillin, high strength aminoglycosides and vancomycin. The majority (78%) of the resistant isolates showed efflux pump activity. Treatment in indoor locations, presence of urinary catheters and pregnancy along with recent exposure to antibiotics especially fluoroquinolones, third generation cephalosporins and piperacillin-tazobactam were identified as independent risk factors. Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance.

  19. In vitro-in vivo extrapolation: estimation of human serum concentrations of chemicals equivalent to cytotoxic concentrations in vitro

    International Nuclear Information System (INIS)

    Guelden, Michael; Seibert, Hasso

    2003-01-01

    In the present study an extrapolation model for estimating serum concentrations of chemicals equivalent to in vitro effective concentrations is developed and applied to median cytotoxic concentrations (EC 50 ) determined in vitro. Nominal concentrations of a chemical in serum and in vitro are regarded as equivalent, if they result in the same aqueous concentration of the unbound form. The algorithm used is based on equilibrium distribution and requires albumin binding data, the octanol-water partition coefficient (K ow ), and the albumin concentrations and lipid volume fractions in vitro and in serum. The chemicals studied cover wide ranges of cytotoxic potency (EC 50 : 2.5-530000 μM) and lipophilicity (log K ow : -5 to 7). Their albumin binding characteristics have been determined by means of an in vitro cytotoxicity test as described previously. The equivalent serum concentrations of 19 of the 33 compounds investigated, having high protein binding and/or lipophilicity, were substantially higher than the EC 50 -values, by factors of 2.5-58. Prominent deviations between the equivalent nominal concentrations in serum and in vitro were largely restricted to chemicals with higher cytotoxic potency (EC 50 ≤1000 μM). The results suggest that estimates of equivalent serum concentrations based on in vitro data are robust for chemicals with low lipophilicity (log K ow ≤2) and low potency (EC 50 >1000 μM). With more potent chemicals or those with higher lipophilicity partitioning into lipids and/or binding to serum proteins have to be taken into account when estimating in vivo serum concentrations equivalent to in vitro effective concentrations

  20. Determination of four fluoroquinolone antibiotics in tap water in Guangzhou and Macao

    International Nuclear Information System (INIS)

    Yiruhan; Wang Qiaojun; Mo Cehui; Li Yanwen; Gao Peng; Tai Yiping; Zhang Yan; Ruan Zhili; Xu Jiawei

    2010-01-01

    Four fluoroquinolone antibiotics (norfloxacin, ciprofloxacin, lomefloxacin, and enrofloxacin) in tap water in Guangzhou and Macao were analyzed using high performance liquid chromatography fluorescence detection. The results showed that all target antibiotics were detected in high rate both in Guangzhou (77.5%) and Macao (100%), ranging from 1.0 to 679.7 ng/L (SD ≤ 37.6) in Guangzhou, and from 2.0 to 37.0 ng/L (SD ≤ 2.5) in Macao. The fluoroquinolone antibiotics pollution in tap water widely distributes in Guangzhou and Macao. In addition, the effect of rainfall on concentration of fluoroquinolone antibiotics in south China was also investigated. Our result indicates that the antibiotic concentration in tap water in Guangzhou tends to obviously reduce at the beginning of rainy season, even decreases below the limit of quantification immediately. Thus, it was clarified that the heavy rain in south China has the function of reducing the fluoroquinolone antibiotics concentrations in tap water. - The antibiotics were detected in the tap water in Guangzhou and Macao using our developed method for fluoresence detection with high performance liquid chromatography

  1. Determination of four fluoroquinolone antibiotics in tap water in Guangzhou and Macao

    Energy Technology Data Exchange (ETDEWEB)

    Yiruhan; Wang Qiaojun [Department of Environmental Engineering, Jinan University, Huangpudadaoxi 601, Guangzhou 510632 (China); Mo Cehui, E-mail: tchmo@jnu.edu.c [Department of Environmental Engineering, Jinan University, Huangpudadaoxi 601, Guangzhou 510632 (China); Li Yanwen; Gao Peng; Tai Yiping; Zhang Yan; Ruan Zhili; Xu Jiawei [Department of Environmental Engineering, Jinan University, Huangpudadaoxi 601, Guangzhou 510632 (China)

    2010-07-15

    Four fluoroquinolone antibiotics (norfloxacin, ciprofloxacin, lomefloxacin, and enrofloxacin) in tap water in Guangzhou and Macao were analyzed using high performance liquid chromatography fluorescence detection. The results showed that all target antibiotics were detected in high rate both in Guangzhou (77.5%) and Macao (100%), ranging from 1.0 to 679.7 ng/L (SD {<=} 37.6) in Guangzhou, and from 2.0 to 37.0 ng/L (SD {<=} 2.5) in Macao. The fluoroquinolone antibiotics pollution in tap water widely distributes in Guangzhou and Macao. In addition, the effect of rainfall on concentration of fluoroquinolone antibiotics in south China was also investigated. Our result indicates that the antibiotic concentration in tap water in Guangzhou tends to obviously reduce at the beginning of rainy season, even decreases below the limit of quantification immediately. Thus, it was clarified that the heavy rain in south China has the function of reducing the fluoroquinolone antibiotics concentrations in tap water. - The antibiotics were detected in the tap water in Guangzhou and Macao using our developed method for fluoresence detection with high performance liquid chromatography

  2. In vivo sodium, potassium, and sperm concentrations in the rat epididymis.

    Science.gov (United States)

    Turner, T T; Hartmann, P K; Howards, S S

    1977-02-01

    In vivo samples of epididymal fluids were obtained through the use of micropuncture techniques. Microsamples from four areas of the rat epididymis were analyzed for Na+ and K+ concentrations and for sperm density. Na+ values declined significantly from caput to corpus epididymidis (P less than 0.01), while K+ and sperm concentrations increased significantly (P less than 0.01). A large water loss from the epididymal lumen was calculated, as well as net losses of both cations. Water losses may be explained on the basis of an active Na+ pump; however, the effect of the absolute values of epididymal Na+ and K+ concentrations on sperm motility and fertility remains unresolved.

  3. Fluoroquinolone Resistance Mechanisms in an Escherichia coli Isolate, HUE1, Without Quinolone Resistance-Determining Region Mutations

    Directory of Open Access Journals (Sweden)

    Toyotaka eSato

    2013-05-01

    Full Text Available Fluoroquinolone resistance can cause major clinical problems. Here, we investigated fluoroquinolone resistance mechanisms in a clinical Escherichia coli isolate, HUE1, which had no mutations quinolone resistance-determining regions (QRDRs of DNA gyrase and topoisomerase IV. HUE1 demonstrated MICs that exceeded the breakpoints for ciprofloxacin, levofloxacin, and norfloxacin. HUE1 harbored oqxAB and qnrS1 on distinct plasmids. In addition, it exhibited lower intracellular ciprofloxacin concentrations and higher mRNA expression levels of efflux pumps and their global activators than did reference strains. The genes encoding AcrR (local AcrAB repressor and MarR (MarA repressor were disrupted by insertion of the transposon IS3-IS629 and a frameshift mutation, respectively. A series of mutants derived from HUE1 were obtained by plasmid curing and gene knockout using homologous recombination. Compared to the MICs of the parent strain HUE1, the fluoroquinolone MICs of these mutants indicated that qnrS1, oqxAB, acrAB, acrF, acrD, mdtK, mdfA, and tolC contributed to the reduced susceptibility to fluoroquinolone in HUE1. Therefore, fluoroquinolone resistance in HUE1 is caused by concomitant acquisition of QnrS1 and OqxAB and overexpression of AcrAB−TolC and other chromosome-encoded efflux pumps. Thus, we have demonstrated that QRDR mutations are not absolutely necessary for acquiring fluoroquinolone resistance in E. coli.

  4. Strategies to enhance the removal of Fluoroquinolones

    OpenAIRE

    Amorim, Catarina L.; Maia, Alexandra S.; Moreira, Irina S.; van Loosdrecht, Mark C.M.; Tiritan, Maria E.; Castro, Paula M.L.

    2013-01-01

    Fluoroquinolones (FQs) are broad-spectrum antibiotics that play an important role in the treatment of serious bacterial infections. Currently, several FQs are available but ciprofloxacin (CPF), ofloxacin (OFL) and norfloxacin (NOR) are amongst the most worldwide prescribed antibiotics. Antibiotics can reach wastewater treatment plants (WWTP) from different routes. Thus removal of these contaminants during the biotreatment process is of major importance in order to avoid their release to other...

  5. Efficient recovery of fluoroquinolone-susceptible and fluoroquinolone-resistant Escherichia coli strains from frozen samples.

    Science.gov (United States)

    Lautenbach, Ebbing; Santana, Evelyn; Lee, Abby; Tolomeo, Pam; Black, Nicole; Babson, Andrew; Perencevich, Eli N; Harris, Anthony D; Smith, Catherine A; Maslow, Joel

    2008-04-01

    We assessed the rate of recovery of fluoroquinolone-resistant and fluoroquinolone-susceptible Escherichia coli isolates from culture of frozen perirectal swab samples compared with the results for culture of the same specimen before freezing. Recovery rates for these 2 classes of E. coli were 91% and 83%, respectively. The majority of distinct strains recovered from the initial sample were also recovered from the frozen sample. The strains that were not recovered were typically present only in low numbers in the initial sample. These findings emphasize the utility of frozen surveillance samples.

  6. Triceps Ruptures After Fluoroquinolone Antibiotics: A Report of 2 Cases.

    Science.gov (United States)

    Shybut, Theodore B; Puckett, Ernest R

    Rupture of the triceps brachii tendon is exceedingly rare, and surgical repair is generally indicated. Fluoroquinolone antibiotics have been implicated in tendon pathology, including tendon ruptures. Triceps rupture has not been previously reported in the setting of fluoroquinolone antibiotic therapy. We present 2 cases of triceps tendon rupture after treatment with fluoroquinolones. In both cases, triceps repair was performed with good outcomes. These cases highlight a risk of fluoroquinolone-induced tendinopathy to athletes. The sports medicine team should be aware of this risk and consider it when choosing antibiotics to treat athletes.

  7. Fluoroquinolone antibiotics in environmental waters: sample preparation and determination.

    Science.gov (United States)

    Speltini, Andrea; Sturini, Michela; Maraschi, Federica; Profumo, Antonella

    2010-04-01

    The aim of this review is to provide a general overview on the analytical methods proposed in the last decade for trace fluoroquinolone (FQ) determination in environmental waters. A large number of studies have been developed on this topic in reason of the importance of their monitoring in the studies of environmental mobility and potential degradation pathways. Every step of the analysis has been carefully considered, with a particular attention to sample preparation, in relationship with the problems involved in the analysis of real matrices. The different strategies to minimise interference from organic matter and to achieve optimal sensitivity, especially important in those samples with lower FQ concentrations, were also highlighted. Results and progress in this field have been described and critically commented. Moreover, a worldwide overview on the presence of FQs in the environmental waters has been reported.

  8. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

    LENUS (Irish Health Repository)

    Costa, Sofia SANTOS

    2011-10-27

    Abstract Background Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones. Results Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds. Conclusions The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential

  9. Global Fluoroquinolone Resistance Epidemiology and Implictions for Clinical Use

    Science.gov (United States)

    Dalhoff, Axel

    2012-01-01

    This paper on the fluoroquinolone resistance epidemiology stratifies the data according to the different prescription patterns by either primary or tertiary caregivers and by indication. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except S. pneumoniae and H. influenzae, causing community-acquired respiratory tract infections. However, 10 to 30% of these isolates harbored first-step mutations conferring low level fluoroquinolone resistance. Fluoroquinolone resistance increased in Enterobacteriaceae causing community acquired or healthcare associated urinary tract infections and intraabdominal infections, exceeding 50% in some parts of the world, particularly in Asia. One to two-thirds of Enterobacteriaceae producing extended spectrum β-lactamases were fluoroquinolone resistant too. Furthermore, fluoroquinolones select for methicillin resistance in Staphylococci. Neisseria gonorrhoeae acquired fluoroquinolone resistance rapidly; actual resistance rates are highly variable and can be as high as almost 100%, particularly in Asia, whereas resistance rates in Europe and North America range from 30% in established sexual networks. In general, the continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some guidelines, for example, treatment of urinary tract, intra-abdominal, skin and skin structure infections, and traveller's diarrhea, or even precludes the use in indications like sexually transmitted diseases and enteric fever. PMID:23097666

  10. In vivo x-ray fluorescence estimation of bone lead concentrations in Queensland adults

    International Nuclear Information System (INIS)

    Price, J.; Baddeley, H.; Kenardy, J.A.; Thomas, B.J.; Thomas, B.W.

    1984-01-01

    A group of 200 Queensland adults without known health problems had in-vivo estimation of finger bone lead concentrations using X-ray fluorescence analysis (XRF). Forty of these subjects had elevated levels of bone lead of 25 ppm or more, consistent with exposure to the metal. Although the correlation between Queensland residence during childhood and raised bone lead levels was not significant, there were significant correlations between childhood residence in a painted wooden house and raised levels, and between occupational exposure and raised levels. Of the 40 subjects with elevated lead levels only two had neither a history of occupational exposure or childhood residence in a wooden house, whereas 11 of the 25 who had a history of both occupational and residential exposure were positive. The data are consistent with lead in housepaint, or absorbed during occupational exposure, being the two major sources of raised bone lead concentrations. (author)

  11. Determination of natural in vivo noble-gas concentrations in human blood.

    Directory of Open Access Journals (Sweden)

    Yama Tomonaga

    Full Text Available Although the naturally occurring atmospheric noble gases He, Ne, Ar, Kr, and Xe possess great potential as tracers for studying gas exchange in living beings, no direct analytical technique exists for simultaneously determining the absolute concentrations of these noble gases in body fluids in vivo. In this study, using human blood as an example, the absolute concentrations of all stable atmospheric noble gases were measured simultaneously by combining and adapting two analytical methods recently developed for geochemical research purposes. The partition coefficients determined between blood and air, and between blood plasma and red blood cells, agree with values from the literature. While the noble-gas concentrations in the plasma agree rather well with the expected solubility equilibrium concentrations for air-saturated water, the red blood cells are characterized by a distinct supersaturation pattern, in which the gas excess increases in proportion to the atomic mass of the noble-gas species, indicating adsorption on to the red blood cells. This study shows that the absolute concentrations of noble gases in body fluids can be easily measured using geochemical techniques that rely only on standard materials and equipment, and for which the underlying concepts are already well established in the field of noble-gas geochemistry.

  12. Reduced blood flow increases the in vivo ammonium ion concentration in the RIF-1 tumor

    International Nuclear Information System (INIS)

    Constantinidis, Ioannis; Gamcsik, Michael P.

    1995-01-01

    Purpose: Previous studies from our laboratory have suggested that pooling of ammonium in tumor tissues may be caused by its inefficient removal due to the poor vasculature commonly found in tumors. The purpose of these experiments was to validate the relationship between tumor ammonium ion concentration and tumor blood flow, and to determine whether large concentrations of ammonium ion detected by Nuclear Magnetic Resonance (NMR) spectroscopy are either produced within the tumor or simply imported into the tumor through the blood stream. Methods and Materials: To test this hypothesis, we reduced blood flow in subcutaneously grown Radiation Induced Fibrosarcoma-1 (RIF-1) tumors, either by creating partial ischemia with a bolus injection of hydralazine or by occlusion with surgical sutures. 14 N and 31 P NMR spectroscopy were used to detect the presence of ammonium, and to assess the bioenergetic status of the tumors, respectively. Results: A correlation between ammonium ion concentration and (PCr(P i )) ratio was established for untreated tumors. An increase in the in vivo tumor ammonium ion concentration was observed for every tumor that experienced a reduction in blood flow caused by either hydralazine injection or suture ligation. Changes in ammonium ion concentration paralleled changes in the bioenergetics of hydralazine-treated tumors. Conclusion: Our results support the hypothesis that a reduction in tumor blood flow is responsible for the accumulation of ammonium in tumors, and that detected ammonium originated from within the tumor

  13. [Hospital fluoroquinolone prescription habits in northern France].

    Science.gov (United States)

    Levent, T; Cabaret, P

    2010-09-01

    The aim of the study was to assess the good use organization and fluoroquinolone prescription habits in cases of bone and joint, urinary, pulmonary, and digestive infections. A declarative survey was made (questionnaire for the hospital and for the prescriber). Thirty percent (44/145) of hospitals participated with 274 prescribers. Eighty percent had prescription protocols, 71 % of clinicians had access to epidemiologic data. A percentage of 30.7 (853/2,771) of prescriptions included a fluoroquinolone, 44.5 % (380/853) among these had not been recommended. The excessive prescription reached 24.4 % (116/474) in case of bone and joint infection, 14.6 % (107/731), and 20 % (157/779) in cases of digestive and respiratory infection respectively. Prescriptions for urinary infection were adequate in 47.6 % (375/787) of cases. Inadequate prescriptions were made because of bad knowledge of bacteria resistance epidemiology and pharmacology (insufficient dose, monotherapy at risk of selection), and non-application of good practice recommendations. This study justifies the rationalization of antibiotic prescription. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  14. Occurrence and risk assessment of four typical fluoroquinolone antibiotics in raw and treated sewage and in receiving waters in Hangzhou, China.

    Science.gov (United States)

    Tong, Changlun; Zhuo, Xiajun; Guo, Yun

    2011-07-13

    A sensitive liquid chromatography-fluorescence detection method, combined with one-step solid-phase extraction, was established for detecting the residual levels of the four typical fluoroquinolone antibiotics (ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin) in influent, effluent, and surface waters from Hangzhou, China. For the various environmental water matrices, the overall recoveries were from 76.8 to 122%, and no obvious interferences of matrix effect were observed. The limit of quantitation of this method was estimated to be 17 ng/L for ciprofloxacin and norfloxacin, 20 ng/L for ofloxacin, and 27 ng/L for enrofloxacin. All of the four typical fluoroquinolone antibiotics were found in the wastewaters and surface waters. The residual contents of the four typical fluoroquinolone antibiotics in influent, effluent, and surface water samples are 108-1405, 54-429, and 7.0-51.6 ng/L, respectively. The removal rates of the selected fluoroquinolone antibiotics were 69.5 (ofloxacin), 61.3 (norfloxacin), and 50% (enrofloxacin), indicating that activated sludge treatment is effective except for ciprofloxacin and necessary to remove these fluoroquinolone antibiotics in municipal sewage. The risk to the aquatic environment was estimated by a ratio of measured environmental concentration and predicted no-effect concentration. At the concentrations, these fluoroquinolone antibiotics were found in influent, effluent, and surface waters, and they should not pose a risk for the aquatic environment.

  15. Biochanin A partially restores the activity of ofloxacin and ciprofloxacin against topoisomerase IV mutation-associated fluoroquinolone-resistant Ureaplasma species.

    Science.gov (United States)

    Jin, Hong; Qi, Chao; Zou, Yanping; Kong, Yingying; Ruan, Zhi; Ding, Honghui; Xie, Xinyou; Zhang, Jun

    2017-11-01

    This study aims to investigate the synergistic antimicrobial activity of four phytoalexins in combination with fluoroquinolones against Ureaplasma spp., a genus of cell wall-free bacteria that are intrinsically resistant to many available antibiotics, making treatment inherently difficult. A total of 22 958 urogenital tract specimens were assessed for Ureaplasma spp. identification and antimicrobial susceptibility. From these, 31 epidemiologically unrelated strains were randomly selected for antimicrobial susceptibility testing to determine the minimum inhibitory concentration (MIC) of four fluoroquinolones and the corresponding quinolone resistance-determining regions (QRDRs). Synergistic effects between fluoroquinolones and four phytoalexins (reserpine, piperine, carvacrol and biochanin A) were evaluated by fractional inhibitory concentration indices (FICIs). Analysis of the QRDRs suggested a vital role for the mutation of Ser-83→Leu in ParC in fluoroquinolone-resistant strains, and the occurrence of mutations in QRDRs showed significant associations with the breakpoint of levofloxacin. Moreover, diverse synergistic effects of the four phytoalexins with ofloxacin or ciprofloxacin were observed and biochanin A was able to enhance the antimicrobial activity of fluoroquinolones significantly. This is the first report of the antimicrobial activity of biochanin A in combination with fluoroquinolones against a pathogenic mycoplasma, and opens up the possibility of using components of biochanin A as a promising therapeutic option for treating antibiotic-resistant Ureaplasma spp. infections.

  16. [Impact of fluoroquinolone use on multidrug-resistant bacteria emergence].

    Science.gov (United States)

    Nseir, S; Ader, F; Marquette, C-H; Durocher, A

    2005-01-01

    During the last two decades, fluoroquinolone use has significantly increased in Europe and in the USA. This could be explained by the arrival of newer fluoroquinolones with antipneumoccal activity. Increased use of fluoroquinolones is associated with higher rates of bacterial resistance to these antibiotics. Resistance of Gram-negative bacilli to fluoroquinolones is increasing in industrialized countries. In addition, fluoroquinolone use has been identified as a risk factor for colonization and infection to methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter baumanni, extending-spectrum beta-lactamase producing Gram negative bacilli, and multidrug-resistant bacteria. Nosocomial infections due to multidrug-resistant bacteria are associated with higher mortality and morbidity rates. This could be related to more frequent inappropriate initial antibiotic treatment in these patients. Limiting the use of fluoroquinolones, limiting the duration of treatment with fluoroquinolones, and using appropriate dosage of these antibiotics could be suggested to reduce resistance to these antibiotics and to reduce the emergence of multidrug-resistant bacteria.

  17. Magnesium degradation influenced by buffering salts in concentrations typical of in vitro and in vivo models

    International Nuclear Information System (INIS)

    Agha, Nezha Ahmad; Feyerabend, Frank; Mihailova, Boriana; Heidrich, Stefanie; Bismayer, Ulrich; Willumeit-Römer, Regine

    2016-01-01

    Magnesium and its alloys have considerable potential for orthopedic applications. During the degradation process the interface between material and tissue is continuously changing. Moreover, too fast or uncontrolled degradation is detrimental for the outcome in vivo. Therefore in vitro setups utilizing physiological conditions are promising for the material/degradation analysis prior to animal experiments. The aim of this study is to elucidate the influence of inorganic salts contributing to the blood buffering capacity on degradation. Extruded pure magnesium samples were immersed under cell culture conditions for 3 and 10 days. Hank's balanced salt solution without calcium and magnesium (HBSS) plus 10% of fetal bovine serum (FBS) was used as the basic immersion medium. Additionally, different inorganic salts were added with respect to concentration in Dulbecco's modified Eagle's medium (DMEM, in vitro model) and human plasma (in vivo model) to form 12 different immersion media. Influences on the surrounding environment were observed by measuring pH and osmolality. The degradation interface was analyzed by electron-induced X-ray emission (EIXE) spectroscopy, including chemical-element mappings and electron microprobe analysis, as well as Fourier transform infrared reflection micro-spectroscopy (FTIR). - Highlights: • Influence of blood buffering salts on magnesium degradation was studied. • CaCl_2 reduced the degradation rate by Ca–PO_4 layer formation. • MgSO_4 influenced the morphology of the degradation interface. • NaHCO_3 induced the formation of MgCO_3 as a degradation product

  18. Magnesium degradation influenced by buffering salts in concentrations typical of in vitro and in vivo models.

    Science.gov (United States)

    Agha, Nezha Ahmad; Feyerabend, Frank; Mihailova, Boriana; Heidrich, Stefanie; Bismayer, Ulrich; Willumeit-Römer, Regine

    2016-01-01

    Magnesium and its alloys have considerable potential for orthopedic applications. During the degradation process the interface between material and tissue is continuously changing. Moreover, too fast or uncontrolled degradation is detrimental for the outcome in vivo. Therefore in vitro setups utilizing physiological conditions are promising for the material/degradation analysis prior to animal experiments. The aim of this study is to elucidate the influence of inorganic salts contributing to the blood buffering capacity on degradation. Extruded pure magnesium samples were immersed under cell culture conditions for 3 and 10 days. Hank's balanced salt solution without calcium and magnesium (HBSS) plus 10% of fetal bovine serum (FBS) was used as the basic immersion medium. Additionally, different inorganic salts were added with respect to concentration in Dulbecco's modified Eagle's medium (DMEM, in vitro model) and human plasma (in vivo model) to form 12 different immersion media. Influences on the surrounding environment were observed by measuring pH and osmolality. The degradation interface was analyzed by electron-induced X-ray emission (EIXE) spectroscopy, including chemical-element mappings and electron microprobe analysis, as well as Fourier transform infrared reflection micro-spectroscopy (FTIR). Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Sublimation thermodynamics of four fluoroquinolone antimicrobial compounds

    International Nuclear Information System (INIS)

    Blokhina, Svetlana; Sharapova, Angelica; Ol’khovich, Marina; Perlovich, German

    2017-01-01

    Highlights: • The vapor pressures of ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin were measured. • The values of enthalpies, entropies and Gibbs energies of sublimation were calculated at T = 298.15 K. • Thermophysical characteristics of the studied compounds were determined. • The influence hydrogen bonds in crystal lattices on the sublimation enthalpy was discussed. - Abstract: The transpiration method was used to measure the vapor pressures as a function of temperature of the following antimicrobial drugs: ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin. Based on these results standard molar enthalpies, entropies and Gibbs energies of sublimation at T = 298.15 K were calculated and a correlation between the crystal lattice energy and the saturation vapor pressure in a number of fluoroquinolones was found. The thermophysical characteristics of the compounds studied were determined by DSC. The influence of different structural fragments of molecules substituents and the effects of hydrogen bonds in crystal lattices on the sublimation enthalpy was discussed.

  20. Estimation of natural potassium concentration in Romanian males by in vivo gamma-ray spectrometry measurements

    International Nuclear Information System (INIS)

    Mirela Angela Saizu

    2012-01-01

    At the Whole Body Monitoring Laboratory, from IFIN-HH, Bucharest, Romania, there were performed in vivo gamma-ray spectrometry measurements on 108 Romanian males in order to evaluate the mineral natural potassium content in human body, as total value and concentration. The measurements were performed with a shadow shield whole body counter, tilted chair geometry, based on a shielded NaI(Tl) scintillation detector of 12.5 cm (diameter) x 10 cm (height) crystal size. The results revealed a calculated value of the mean total body potassium (TBK) of 135.03 ± 2.94 g and a value of 1.9 ± 0.022 g of potassium/kg of body weight for the mean body potassium concentration, for the measured males. These values are similar with the values declared for the Reference Man, in ICRP23. Correlations between total body potassium, potassium concentration and age, weight and Body Build Index were investigated and peculiar conclusions were resulted. (author)

  1. In Vivo Dentate Nucleus Gamma-aminobutyric Acid Concentration in Essential Tremor vs. Controls.

    Science.gov (United States)

    Louis, Elan D; Hernandez, Nora; Dyke, Jonathan P; Ma, Ruoyun E; Dydak, Ulrike

    2018-04-01

    Despite its high prevalence, essential tremor (ET) is among the most poorly understood neurological diseases. The presence and extent of Purkinje cell (PC) loss in ET is the subject of controversy. PCs are a major storehouse of central nervous system gamma-aminobutyric acid (GABA), releasing GABA at the level of the dentate nucleus. It is therefore conceivable that cerebellar dentate nucleus GABA concentration could be an in vivo marker of PC number. We used in vivo 1 H magnetic resonance spectroscopy (MRS) to quantify GABA concentrations in two cerebellar volumes of interest, left and right, which included the dentate nucleus, comparing 45 ET cases to 35 age-matched controls. 1 H MRS was performed using a 3.0-T Siemens Tim Trio scanner. The MEGA-PRESS J-editing sequence was used for GABA detection in two cerebellar volumes of interest (left and right) that included the dentate nucleus. The two groups did not differ with respect to our primary outcome of GABA concentration (given in institutional units). For the right dentate nucleus, [GABA] in ET cases = 2.01 ± 0.45 and [GABA] in controls = 1.86 ± 0.53, p = 0.17. For the left dentate nucleus, [GABA] in ET cases = 1.68 ± 0.49 and [GABA] controls = 1.80 ± 0.53, p = 0.33. The controls had similar dentate nucleus [GABA] in the right vs. left dentate nucleus (p = 0.52); however, in ET cases, the value on the right was considerably higher than that on the left (p = 0.001). We did not detect a reduction in dentate nucleus GABA concentration in ET cases vs. One interpretation of the finding is that it does not support the existence of PC loss in ET; however, an alternative interpretation is the observed pattern could be due to the effects of terminal sprouting in ET (i.e., collateral sprouting from surviving PCs making up for the loss of GABA-ergic terminals from PC degeneration). Further research is needed.

  2. Exposure to low mercury concentration in vivo impairs myocardial contractile function

    International Nuclear Information System (INIS)

    Furieri, Lorena Barros; Fioresi, Mirian; Junior, Rogerio Faustino Ribeiro; Bartolome, Maria Visitacion; Fernandes, Aurelia Araujo; Cachofeiro, Victoria; Lahera, Vicente; Salaices, Mercedes; Stefanon, Ivanita; Vassallo, Dalton Valentim

    2011-01-01

    Increased cardiovascular risk after mercury exposure has been described but cardiac effects resulting from controlled chronic treatment are not yet well explored. We analyzed the effects of chronic exposure to low mercury concentrations on hemodynamic and ventricular function of isolated hearts. Wistar rats were treated with HgCl 2 (1st dose 4.6 μg/kg, subsequent dose 0.07 μg/kg/day, im, 30 days) or vehicle. Mercury treatment did not affect blood pressure (BP) nor produced cardiac hypertrophy or changes of myocyte morphometry and collagen content. This treatment: 1) in vivo increased left ventricle end diastolic pressure (LVEDP) without changing left ventricular systolic pressure (LVSP) and heart rate; 2) in isolated hearts reduced LV isovolumic systolic pressure and time derivatives, and β-adrenergic response; 3) increased myosin ATPase activity; 4) reduced Na + -K + ATPase (NKA) activity; 5) reduced protein expression of SERCA and phosphorylated phospholamban on serine 16 while phospholamban expression increased; as a consequence SERCA/phospholamban ratio reduced; 6) reduced sodium/calcium exchanger (NCX) protein expression and α-1 isoform of NKA, whereas α-2 isoform of NKA did not change. Chronic exposure for 30 days to low concentrations of mercury does not change BP, heart rate or LVSP but produces small but significant increase of LVEDP. However, in isolated hearts mercury treatment promoted contractility dysfunction as a result of the decreased NKA activity, reduction of NCX and SERCA and increased PLB protein expression. These findings offer further evidence that mercury chronic exposure, even at small concentrations, is an environmental risk factor affecting heart function. - Highlights: → Unchanges blood pressure, heart rate, systolic pressure. → Increases end diastolic pressure. → Promotes cardiac contractility dysfunction. → Decreases NKA activity, NCX and SERCA, increases PLB protein expression. → Small concentrations constitutes

  3. Fluoroquinolones in the treatment of Actinobacillus actinomycetemcomitans associated periodontitis

    NARCIS (Netherlands)

    Kleinfelder, JW; Mueller, RF; Lange, DE

    Background: Periodontitis patients harboring Actinobacillus actinmycetemcomitans (Aa) are prime candidates for systemic antibiotic therapy. Besides tetracycline and the combination of metronidazole and amoxicillin the fluoroquinolones are also believed to have antibacterial activity against Aa. The

  4. Biological activities of some Fluoroquinolones-metal complexes

    African Journals Online (AJOL)

    McRoy

    DNA cleavage studies of some synthesized metal complexes of fluoroquinolone ... Although the FQs are generally characterized by a broad antimicrobial spectrum ..... six Coordinate 3rd metal complexes with N- (5 –Phenyl-3,4- thiadiazol-2-yl).

  5. Magnesium degradation influenced by buffering salts in concentrations typical of in vitro and in vivo models

    Energy Technology Data Exchange (ETDEWEB)

    Agha, Nezha Ahmad; Feyerabend, Frank [Helmholtz-Zentrum Geesthacht, Institute of Material Research, Division of Metallic Biomaterials, Max-Planck-Str. 1, 21502 Geesthacht (Germany); Mihailova, Boriana; Heidrich, Stefanie; Bismayer, Ulrich [University of Hamburg, Department of Earth Sciences, Grindelallee 48, 20146 Hamburg (Germany); Willumeit-Römer, Regine [Helmholtz-Zentrum Geesthacht, Institute of Material Research, Division of Metallic Biomaterials, Max-Planck-Str. 1, 21502 Geesthacht (Germany)

    2016-01-01

    Magnesium and its alloys have considerable potential for orthopedic applications. During the degradation process the interface between material and tissue is continuously changing. Moreover, too fast or uncontrolled degradation is detrimental for the outcome in vivo. Therefore in vitro setups utilizing physiological conditions are promising for the material/degradation analysis prior to animal experiments. The aim of this study is to elucidate the influence of inorganic salts contributing to the blood buffering capacity on degradation. Extruded pure magnesium samples were immersed under cell culture conditions for 3 and 10 days. Hank's balanced salt solution without calcium and magnesium (HBSS) plus 10% of fetal bovine serum (FBS) was used as the basic immersion medium. Additionally, different inorganic salts were added with respect to concentration in Dulbecco's modified Eagle's medium (DMEM, in vitro model) and human plasma (in vivo model) to form 12 different immersion media. Influences on the surrounding environment were observed by measuring pH and osmolality. The degradation interface was analyzed by electron-induced X-ray emission (EIXE) spectroscopy, including chemical-element mappings and electron microprobe analysis, as well as Fourier transform infrared reflection micro-spectroscopy (FTIR). - Highlights: • Influence of blood buffering salts on magnesium degradation was studied. • CaCl{sub 2} reduced the degradation rate by Ca–PO{sub 4} layer formation. • MgSO{sub 4} influenced the morphology of the degradation interface. • NaHCO{sub 3} induced the formation of MgCO{sub 3} as a degradation product.

  6. Triprotic site-specific acid-base equilibria and related properties of fluoroquinolone antibacterials.

    Science.gov (United States)

    Rusu, Aura; Tóth, Gergő; Szőcs, Levente; Kökösi, József; Kraszni, Márta; Gyéresi, Árpád; Noszál, Béla

    2012-07-01

    The complete macro- and microequilibrium analyses of six fluoroquinolone drugs - ciprofloxacin, enrofloxacin, norfloxacin, pefloxacin, ofloxacin and moxifloxacin - are presented. Previous controversial literature data are straightened up, the protonation centers are unambiguously identified, and the protonation macro- and microconstant values are reported. The macroconstants were determined by (1)H NMR-pH titrations while the microconstants were determined by a multi-modal spectroscopic-deductive methodology, in which methyl ester derivatives were synthesized and their NMR-pH titration data contributed to the evaluation of all the microconstants. The full (1)H, (13)C and (15)N NMR assignments, NMR-pH profiles, macro- and microprotonation schemes and species-specific diagrams are included. Our studies show that the fluoroquinolones have three protonation centers: the carboxylate group, the N-1' and N-4' piperazine nitrogens and concentration of the uncharged microspecies is way below the values published earlier. The results could be well interpreted in terms of structural properties. The protonation macro- and microconstant values allow the pre-planned method development in techniques such as capillary zone electrophoresis and also, the interpretation of fluoroquinolone mechanism of biological action, including the pharmacokinetic properties, and antibacterial activities that are all heavily influenced by the states of protonation. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Determination of Tetracycline and Fluoroquinolone Antibiotics at Trace Levels in Sludge and Soil

    Directory of Open Access Journals (Sweden)

    Marie-Virginie Salvia

    2015-01-01

    Full Text Available This work describes the development of a sensitive analytical method to determine simultaneously traces of tetracycline and fluoroquinolone antibiotics in sludge and soil, based on PLE extraction, followed by SPE purification and finally an analysis by LC-MS/MS. Recoveries were greater than 87% in the case of fluoroquinolones and between 25.4 and 41.7% for tetracyclines. Low relative standard deviations (<15% were obtained in both matrices. The limits of quantification were comprised between 1.1 and 4.6 ng/g and between 5 and 20 ng/g in soil and sludge, respectively. The method was then successfully applied to the analysis of the target antibiotics in sludge as well as soil that received spreading. The substances most frequently found and with the highest levels were fluoroquinolones with concentrations exceeding 1,000 ng/g in several samples of sludge and up to 16 ng/g in soil.

  8. Characterization of fluoroquinolone resistance and qnr diversity in Enterobacteriaceae from municipal biosolids.

    Directory of Open Access Journals (Sweden)

    Ella eKaplan

    2013-06-01

    Full Text Available Municipal biosolids produced during activated sludge treatment applied in waste water treatment plants, are significant reservoirs of antibiotic resistance, since they assemble both natural and fecal microbiota, as well as residual concentrations of antibiotic compounds. This raises major concerns regarding the environmental and epidemiological consequences of using them as fertilizers for crops. The second generation fluoroquinolone ciprofloxacin is probably the most abundant antibiotic compound detected in municipal biosolids due to its widespread use and sorption properties. Although fluoroquinolone resistance was originally thought to result from mutations in bacterial gyrase and topoisomerase IV genes, it is becoming apparent that it is also attributed to plasmid-associated resistance factors, which may propagate environmental antibiotic resistance. The objective of this study was to assess the impact of the activated sludge process on fluoroquinolone resistance. The scope of resistances and mobile genetic mechanisms associated with fluoroquinolone resistance were evaluated by screening large collections of ciprofloxacin-resistant Enterobacteriaceae strains from sludge (n=112 and from raw sewage (n=89. Plasmid-mediated quinolone resistance determinants (qnrA, B and S were readily detected in isolates from both environments, the most dominant being qnrS. Interestingly, all qnr variants were significantly more abundant in sludge isolates than in the isolates from raw sewage. Almost all of ciprofloxacin-resistant isolates were resistant to multiple antibiotic compounds. The sludge isolates were on the whole resistant to a broader range of antibiotic compounds than the raw sewage isolates; however this difference was not statistically significant. Collectively, this study indicates that the activated sludge selects for multiresistant bacterial strains, and that mobile quinolone-resistance elements may have a selective advantage in the activated

  9. Pulse radiolysis study on several fluoroquinolones

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Peng [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Graduate University of Chinese Academy of Science, Beijing 100049 (China); Yao Side [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Li Haixia; Song Xiyu; Liu Yancheng [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China); Graduate University of Chinese Academy of Science, Beijing 100049 (China); Wang Wenfeng, E-mail: wangwenfeng@sinap.ac.c [Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800 (China)

    2011-04-15

    Reactions of several fluoroquinolones (FQs), including enoxacin, norfloxacin, and ciprofloxacin, with various reactive species such as e{sub aq}{sup -}, N{sup {center_dot}}{sub 3}, and {sup {center_dot}O}H are investigated by pulse radiolysis techniques. The FQ radical anions formed in the reactions of FQs with e{sub aq}{sup -} could either be protonated or deprotonated, and the absorption of FQ radical anions was located around 370 nm. The absorption of the neutral radicals produced in the protonation, and the radical dianions produced in the deprotonation of FQ radical anions were located in the 500-750 nm region. The FQ radical cations formed in the reactions of FQs with N{sub 3}{sup {center_dot}} showed an absorption band around 360 nm. Due to the strong bleaching below 350 nm, the absorption maxima ({lambda}{sub max}) of FQ radical anions, and the {lambda}{sub max} of FQ radical cations were not confirmed. The absorption of the FQ radical anions and cations was clearly pH dependent. Under neutral conditions, the reaction rate constants of FQs with e{sub aq}{sup -} and {sup {center_dot}O}H, which are diffusion controlled, were determined.

  10. Fluoroquinolones and qnr genes in sediment, water, soil, and human fecal flora in an environment polluted by manufacturing discharges.

    Science.gov (United States)

    Rutgersson, Carolin; Fick, Jerker; Marathe, Nachiket; Kristiansson, Erik; Janzon, Anders; Angelin, Martin; Johansson, Anders; Shouche, Yogesh; Flach, Carl-Fredrik; Larsson, D G Joakim

    2014-07-15

    There is increasing concern that environmental antibiotic pollution promotes transfer of resistance genes to the human microbiota. Here, fluoroquinolone-polluted river sediment, well water, irrigated farmland, and human fecal flora of local villagers within a pharmaceutical industrial region in India were analyzed for quinolone resistance (qnr) genes by quantitative PCR. Similar samples from Indian villages farther away from industrial areas, as well as fecal samples from Swedish study participants and river sediment from Sweden, were included for comparison. Fluoroquinolones were detected by MS/MS in well water and soil from all villages located within three km from industrially polluted waterways. Quinolone resistance genes were detected in 42% of well water, 7% of soil samples and in 100% and 18% of Indian and Swedish river sediments, respectively. High antibiotic concentrations in Indian sediment coincided with high abundances of qnr, whereas lower fluoroquinolone levels in well water and soil did not. We could not find support for an enrichment of qnr in fecal samples from people living in the fluoroquinolone-contaminated villages. However, as qnr was detected in 91% of all Indian fecal samples (24% of the Swedish) it suggests that the spread of qnr between people is currently a dominating transmission route.

  11. Reduced red cell 2,3-diphosphoglycerate concentrations in critical illness without decreased in vivo P50.

    Science.gov (United States)

    Morgan, T J; Koch, D; Morris, D; Clague, A; Purdie, D M

    2001-10-01

    We investigated whether red cell 2,3-diphosphoglycerate (2,3-DPG) concentrations are reduced in critical illness, whether acidaemia, hypophosphataemia or anaemia influence 2,3-DPG, and whether there is any net effect on in vivo P50. Twenty healthy, non-smoking, male volunteers were compared with 20 male intensive care patients with APACHE 2 scores >20 on the preceding day. Those transfused in this time were excluded. Venous red cell 2,3-DPG concentrations were measured in both groups. In the patient group, routine multichannel biochemical profile and arterial blood gas analysis were also performed and in vivo P50 calculated. The mean 2,3-DPG concentration was significantly lower in the patient group than in the controls (4.2+/-1.3 mmol/l vs 4.9+/-0.5 mmol/l, P=0.016). The patients were well oxygenated (lowest arterial PO2=75 mm Hg) and showed a tendency to acidaemia (median pH 7.37, range 7.06 to 7.48) and anaemia (median haemoglobin concentration 113 g/l, range 89 to 154 g/l). By linear regression of patient data, pH had a significant effect on 2,3-DPG concentrations (r=0.6, P=0.011). Haemoglobin and phosphate concentrations did not, but there were few abnormal phosphate values. There was no correlation between 2,3-DPG concentrations and in vivo P50 (r2 < or = 0.08). We conclude that 2,3-DPG concentrations were reduced in a broad group of critically ill patients. Although this would normally reduce the P50, the reduction was primarily linked with acidaemia, which increases the P50. Overall, there was no net effect on the P50 and thus no affinity-related decrease in tissue oxygenation.

  12. Resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients

    Directory of Open Access Journals (Sweden)

    Nafees Ahmad

    2016-01-01

    Conclusion: The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public–private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.

  13. Validation of NIRS in measuring tissue hemoglobin concentration and oxygen saturation on ex vivo and isolated limb models

    Science.gov (United States)

    Xu, Xiaorong; Zhu, Wen; Padival, Vikram; Xia, Mengna; Cheng, Xuefeng; Bush, Robin; Christenson, Linda; Chan, Tim; Doherty, Tim; Iatridis, Angelo

    2003-07-01

    Photonify"s tissue spectrometer uses Near-Infrared Spectroscopy for real-time, noninvasive measurement of hemoglobin concentration and oxygen saturation [SO2] of biological tissues. The technology was validated by a series of ex vivo and animal studies. In the ex vivo experiment, a close loop blood circulation system was built, precisely controlling the oxygen saturation and the hemoglobin concentration of a liquid phantom. Photonify"s tissue spectrometer was placed on the surface of the liquid phantom for real time measurement and compared with a gas analyzer, considered the gold standard to measure oxygen saturation and hemoglobin concentration. In the animal experiment, the right hind limb of each dog accepted onto the study was surgically removed. The limb was kept viable by connecting the femoral vein and artery to a blood-primed extracorporeal circuit. Different concentrations of hemoglobin were obtained by adding designated amount of saline solution into the perfusion circuit. Photonify"s tissue spectrometers measured oxygen saturation and hemoglobin concentration at various locations on the limb and compared with gas analyzer results. The test results demonstrated that Photonify"s tissue spectrometers were able to detect the relative changes in tissue oxygen saturation and hemoglobin concentration with a high linear correlation compared to the gas analyzer

  14. Degradation of two fluoroquinolone antibiotics photoinduced by Fe(III)-microalgae suspension in an aqueous solution.

    Science.gov (United States)

    Ge, Liyun; Deng, Huanhuan

    2015-04-01

    The widespread presence of fluoroquinolone antibiotics (FQs) in natural ecosystems is a health hazard for humans and other living organisms. In this work, the photochemical degradation process of two antibiotics in the presence of Fe(III) and marine microalgae has been studied. Two fluoroquinolone (FQ) antibiotics, enrofloxacin (ENR) and ciprofloxacin hydrochloride (CIP), and two marine microalgae, Platymonas subcordiformis and Isochrysis galbana, were investigated under irradiation with a high-pressure mercury lamp (HPML) in a laboratory-scale experiment. The effects of the initial concentration of antibiotics on the degradation of these two FQs in Fe(III)-algae suspensions were also investigated. On the basis of the information in this study, compared to other systems, the efficiency of photo-degradation of the two FQs is better at lower FQ concentrations in the Fe(III)-algae system. Moreover, the low initial concentration of antibiotics benefits the photochemical process of antibiotics. This work demonstrated that the Fe(III)-algae system is an interesting and valuable research area and could be considered as a promising photochemical system for seawater remediation.

  15. Overview and experience with the use of fluoroquinolone in children ...

    African Journals Online (AJOL)

    The use of fluoroquinolone is contraindicated in children because of the potential complication of arthropathy. In spite of this, the role of ciprofloxacin is becoming increasingly significant. We report two cases in which organisms that did not respond to the use of some other potent antibiotics clearly responded to the use of ...

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

    Science.gov (United States)

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

    2013-08-01

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

  17. Ozone pretreatment of process waste water generated in course of fluoroquinolone production.

    Science.gov (United States)

    Daoud, Fares; Pelzer, David; Zuehlke, Sebastian; Spiteller, Michael; Kayser, Oliver

    2017-10-01

    During production of active pharmaceutical ingredients, process waste water is generated at several stages of manufacturing. Whenever possible, the resulting waste water will be processed by conventional waste water treatment plants. Currently, incineration of the process waste water is the method to eliminate compounds with high biological activity. Thus, ozone treatment followed by biological waste water treatment was tested as an alternative method. Two prominent representatives of the large group of fluoroquinolone antibiotics (ciprofloxacin and moxifloxacin) were investigated, focussing on waste water of the bulk production. Elimination of the target compounds and generation of their main transformation products were determined by liquid chromatography - high resolution mass spectrometry (LC-HRMS). The obtained results demonstrated, that the concentration of moxifloxacin and its metabolites can be effectively reduced (>99.7%) prior entering the receiving water. On the contrary, the concentration of ciprofloxacin and its metabolites remained too high for safe discharge, necessitating application of prolonged ozonation for its further degradation. The required ozonation time can be estimated based on the determined kinetics. To assure a low biological activity the ecotoxicity of the ozonated waste water was investigated using three trophic levels. By means of multiple-stage mass spectrometry (MS n ) experiments several new transformation products of the fluoroquinolones were identified. Thus, previously published proposed structures could be corrected or confirmed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Non-invasive determination of metabolite concentrations in human transplanted kidney in vivo by 31P MR spectroscopy

    International Nuclear Information System (INIS)

    Kugel, H.; Wittsack, H.J.; Wenzel, F.; Heindel, W.; Lackner, K.; Stippel, D.

    2000-01-01

    To investigate concentrations of phosphorus-containing metabolites in human transplanted kidney in vivo by quantitative 31 P MR spectroscopy (MRS) using surface coils and to compare the obtained values with previous data. Material and Methods: In 5 patients with well-functioning transplanted kidneys, 31 P spectra were obtained with the three-dimensional localization image-selected in vivo spectroscopy technique applying a protocol for quantitative spectroscopy using surface coils. Relaxation corrected signal intensities determined by time domain fitting were used to derive absolute molar concentrations for phosphate-containing metabolites. Results: Little or no phosphocreatine in all spectra verified the absence of muscle contamination, confirming proper volume localization. The mean concentrations in the transplanted kidneys were as follows: ATP 1.60±0.26 mmol/l, PDE 2.14±0.91 mmol/l, Pi 0.66±0.25 mmol/l, PME 2.32±0.50 mmol/l. These values are consistent with previously reported values determined by other techniques. Conclusion: The non-invasive determination of absolute metabolite concentrations in human kidney using MRS supplements the use of signal intensity ratios to detect pathologic changes in the energy metabolism of transplanted kidneys

  19. Study of the separation of fluoroquinolones using HPLC: Application to the study of their degradation by gamma radiation

    International Nuclear Information System (INIS)

    Ben Saad, Latifa

    2013-01-01

    A method of high performance liquid chromatography (HPLC) in reverse phase was developed for the separation of a mixture of five fluoroquinolones (lomefloxacin, ciprofloxacin, levofloxacin, enoxacin and enrofloxacin). The optimum operating conditions are: the wavelength of detection is fixed at 282nm DAD detector, the stationary phase consists of silica type X scratched Terra RP-18 (250mm x 4, 6 mm, 5μm) and the mobile phase consisted of acetonitrile and phosphate buffer (0.02 M) (20: 80 v: v), pH equal to flow rate of 1ml/M/Xin 3etde. This optimized method was applied to analyze the solutions of different concentrations of each fluoroquinolone (100 and 20 ppm) after irradiation with doses of gamma radiation (5 and 25 kGry). The study of the effect of such radiation on fluoroquinolones shows that with a dose of 5 kGry these radiations allow complete degradation of these active ingredients at a concentration of 20 ppm and the appearance of other degradation products. But a dose of 5 kGry is insufficient to degrade the active ingredients (100ppm).

  20. Impact of bioavailability on the correlation between in vitro cytotoxic and in vivo acute fish toxic concentrations of chemicals

    International Nuclear Information System (INIS)

    Guelden, Michael; Seibert, Hasso

    2005-01-01

    The lower sensitivity of in vitro cytotoxicity assays currently restricts their use as alternative to the fish acute toxicity assays for hazard assessment of chemicals in the aquatic environment. In vitro cytotoxic potencies mostly refer to nominal concentrations. The main objective of the present study was to investigate, whether a reduced availability of chemicals in vitro can account for the lower sensitivity of in vitro toxicity test systems. For this purpose, the bioavailable free fractions of the nominal cytotoxic concentrations (EC 50 ) of chemicals determined with a cytotoxicity test system using Balb/c 3T3 cells and the corresponding free cytotoxic concentrations (ECu 50 ) were calculated. The algorithm applied is based on a previously developed simple equilibrium distribution model for chemicals in cell cultures with serum-supplemented culture media. This model considers the distribution of chemicals between water, lipids and serum albumin. The algorithm requires the relative lipid volume of the test system, the octanol-water partition coefficient (K ow ) and the in vitro albumin-bound fraction of the chemicals. The latter was determined from EC 50 -measurements in the presence of different albumin concentrations with the Balb/c 3T3 test system. Organic chemicals covering a wide range of cytotoxic potency (EC 50 : 0.16-527000 μM) and lipophilicity (log K ow : -5.0-6.96) were selected, for which fish acute toxicity data (LC 50 -values) from at least one of the three fish species, medaka, rainbow trout and fathead minnow, respectively, were available. The availability of several chemicals was shown to be extensively reduced either by partitioning into lipids or by serum albumin binding, or due to both mechanisms. Reduction of bioavailability became more important with increasing cytotoxic potency. The sensitivity of the Balb/c 3T3 cytotoxicity assay and the correspondence between in vivo and in vitro toxic potencies were increased when the free cytotoxic

  1. A near infrared instrument to monitor relative hemoglobin concentrations of human bone tissue in vitro and in vivo

    Science.gov (United States)

    Aziz, Syed Mahfuzul; Khambatta, Faram; Vaithianathan, Tharshan; Thomas, John C.; Clark, Jillian M.; Marshall, Ruth

    2010-04-01

    A continuous wave near infrared instrument has been developed to monitor in vivo changes in the hemoglobin concentration of the trabecular compartment of human bone. The transmitter uses only two laser diodes of wavelengths 685 and 830 nm, and the receiver uses a single silicon photodiode operating in the photovoltaic mode. The functioning of the instrument and the depth of penetration of the near infrared signals was determined in vitro using tissue-equivalent phantoms. The instrument achieves a depth of penetration of approximately 2 cm for an optode separation of 4 cm and, therefore, has the capacity to interrogate the trabecular compartment of human bone. The functioning of the instrument was tested in vivo to evaluate the relative oxy-hemoglobin (HbO2) and deoxy-hemoglobin (Hb) concentrations of the proximal tibial bone of apparently healthy, normal weight, adult subjects in response to a 3 min on, 5 min off, vascular occlusion protocol. The traces of the relative Hb and HbO2 concentrations obtained were reproducible in controlled conditions. The instrument is relatively simple and flexible, and offers an inexpensive platform for further studies to obtain normative data for healthy cohorts, and to evaluate disease-specific performance characteristics for cohorts with vasculopathies of bone.

  2. Therapeutic administration of enrofloxacin in mice does not select for fluoroquinolone resistance in Campylobacter jejuni.

    Science.gov (United States)

    Inglis, G Douglas; Zaytsoff, S J M; Selinger, L Brent; Taboada, Eduardo N; Uwiera, R R E

    2018-05-11

    Enrofloxacin is registered for therapeutic use in beef cattle to treat bovine respiratory disease in Canada. A murine model was used to experimentally examine the impact of therapeutic administration of enrofloxacin on fluoroquinolone resistance development in Campylobacter jejuni. Administration of enrofloxacin to mice via subcutaneous injection or per os routes resulted in equivalent levels of bioactive enrofloxacin within the intestine, but bioactivity was short-lived (Enrofloxacin administration did not affect densities of total bacteria, Firmicutes, or Bacteroidetes in digesta, and had modest impacts on densities of Enterobacteriaceae. All mice inoculated with C. jejuni NCTC 11168 became persistently colonized by the bacterium. Enrofloxacin reduced C. jejuni cell densities within the cecal and colonic digesta for all treatments, and densities shed in feces as a function of antibiotic duration. None of the C. jejuni isolates recovered from mice after administration of enrofloxacin (n=260) developed resistance to ciprofloxacin regardless of method or duration of administration. Furthermore, only modest shifts in the minimum inhibitory concentration of the isolates by treatment were noted. The study findings indicate that the risk posed by short-term subcutaneous administration of enrofloxacin for the development of fluoroquinolone resistance in mammals is low.

  3. Multiresidue determination of fluoroquinolone, sulfonamide, trimethoprim, and chloramphenicol antibiotics in urban waters in China.

    Science.gov (United States)

    Peng, Xianzhi; Tan, Jianhua; Tang, Caiming; Yu, Yiyi; Wang, Zhendi

    2008-01-01

    A feasible method has been optimized to simultaneously determine multiclass antibiotic residues, including sulfonamides, fluoroquinolones, trimethoprim, and chloramphenicol in urban riverine water and wastewater by off-line solid phase extraction and high-performance liquid chromatography coupled with a diode-array ultraviolet detector and a fluorescence detector. Internal standard and standard addition methods were used in combination to identify and quantify these antibiotics to compensate for the matrix interference. The method quantification limits (MQLs) were determined to be 0.035 to 0.100 microg/L and 0.100 to 0.300 microg/L for the riverine water and wastewater, respectively. Recoveries of the investigated antibiotics ranged from 63 to 126%. Sulfamethoxazole was the most frequently detected antibiotic residue in Guangzhou section of the Major Pearl River, South China, with a maximum level of 0.510 microg/L. Fluoroquinolone antibiotics were relatively less detected with a maximum level of 0.459 microg/L. The maximum concentration of sulfamethoxazole reached 5.597 microg/L in the raw wastewater from a large-scale sewage treatment plant in Guangzhou city. Around 30% of sulfamethoxazole might survive the primary clarification and biotreatment processes in the sewage treatment plant. None of the investigated antibiotics have been found above MQLs in the final effluent after chlorine disinfection.

  4. Subspecies distribution and macrolide and fluoroquinolone resistance genetics of Mycobacterium abscessus in Korea.

    Science.gov (United States)

    Kim, J; Sung, H; Park, J-S; Choi, S-H; Shim, T-S; Kim, M-N

    2016-01-01

    Treating Mycobacterium abscessus infections with antimicrobials remains difficult, possibly due to drug resistance. To investigate the subspecies distribution of M. abscessus and its correlation with antibiotic susceptibility and the genetics of antibiotic resistance, focusing on macrolides and fluoroquinolones, in the Republic of Korea. A total of 53 M. abscessus isolates were identified to the subspecies level by sequencing of hsp65 and erm(41). The minimal inhibitory concentrations (MICs) of clarithromycin (CLM) and ciprofloxacin (CFX) were determined using Sensititre™ RAPMYCO plates. The rrl, gyrA and gyrB genes were sequenced to elucidate the molecular mechanisms of macrolide and fluoroquinolone resistance. Isolates included 22 M. abscessus subsp. abscessus and 31 M. abscessus subsp. bolletii. erm(41) sequences showing subspecies-specific deletions and sequence variations in the 28th nucleotide were concordant with inducible CLM resistance; however, mutations in rrl were not detected. Low- and high-level CFX resistance was observed in respectively 19 (35.8%) and 10 (18.9%) of the 53 clinical isolates, regardless of subspecies. However, no non-synonymous mutations were detected in gyrA or gyrB. Sequencing of the erm gene and subspeciation of M. abscessus may be used to predict inducible macrolide susceptibility. Further studies of the relationship between specific mutations in gyrA or gyrB to MIC change are required.

  5. Fluoroquinolone residues in raw meat from open markets in Ibadan, Southwest, Nigeria

    Directory of Open Access Journals (Sweden)

    Adekunbi Bridget Omotoso

    2015-07-01

    Full Text Available Misuse of fluoroquinolones in livestock production may lead to the presence of their residues in tissues of meat animals after slaughter, constituting health hazards to consumers. The present study was designed to screen for residues of three fluoroquinolones (ciprofloxacin, norfloxacin and ofloxacin in raw meat. Microbiological assay, followed by High Performance Liquid Chromatography (HPLC was used to screen three hundred and twenty samples of beef, chicken, pork and chevon purchased from open markets. Initial screening by microbiological assay revealed that 50%, 55%, 40% and 40% of beef, chicken, pork and chevon, respectively were positive for residues of antibiotics. Further analysis by HPLC with UV detection revealed the presence of ciprofloxacin, norfloxacin and ofloxacin at varying concentrations in the meat samples. Ofloxacin was the least in frequency and abundance in all meat types. Results obtained in this study have implications for public health and will lead to steps that will further enhance the safety of animal foods in order to protect consumers and the animal production industry

  6. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation.

    Science.gov (United States)

    Gabardi, Steven; Waikar, Sushrut S; Martin, Spencer; Roberts, Keri; Chen, Jie; Borgi, Lea; Sheashaa, Hussein; Dyer, Christine; Malek, Sayeed K; Tullius, Stefan G; Vadivel, Nidyanandh; Grafals, Monica; Abdi, Reza; Najafian, Nader; Milford, Edgar; Chandraker, Anil

    2010-07-01

    Nearly 30% of renal transplant recipients develops BK viremia, a prerequisite for BK nephropathy. Case reports have evaluated treatment options for BK virus, but no controlled studies have assessed prophylactic therapies. Fluoroquinolone antibiotics were studied for prevention of BK viremia after renal transplantation. This retrospective analysis evaluated adult renal transplant recipients with at least one BK viral load (blood) between 90 and 400 days after transplantation. Six to 12 months of co-trimoxazole was used for Pneumocystis prophylaxis. In sulfa-allergic/-intolerant patients, 6 to 12 months of atovaquone with 1 month of a fluoroquinolone was used. Fluoroquinolones can inhibit BK DNA topoisomerase. The two groups studied were those that received 30 days of levofloxacin or ciprofloxacin after transplantation and those that did not. The primary endpoint was BK viremia rates at 1 year. Of note, of the 160 patients not receiving fluoroquinolone prophylaxis, 40 received a fluoroquinolone for treatment of a bacterial infection within 3 months after transplantation. Subgroup analysis evaluating these 40 patients against the 120 who had no exposure to fluoroquinolones was completed. A 1-month fluoroquinolone course after transplantation was associated with significantly lower rates of BK viremia at 1 year compared with those with no fluoroquinolone. In the subgroup analysis, exposure to fluoroquinolone for treatment of bacterial infections within 3 months after transplantation was associated with significantly lower 1-year rates of BK viremia. This analysis demonstrates that fluoroquinolones are effective at preventing BK viremia after renal transplantation.

  7. In vivo quantitation of metabolite concentrations in the brain by means of proton MRS

    DEFF Research Database (Denmark)

    Henriksen, O

    1995-01-01

    MRS offers unique possibilities for non-invasive studies of biochemistry in the human brain in vivo. A growing body of evidence suggests that proton MRS may contribute to the clinical evaluation of a number of pathologies including ischaemia, tumours, epilepsy, metabolic and neuropaediatric...... (kg wet weight)-1 range between 8.2 and 17.2 (mean 10.2), 5.9 and 11.6 (mean 7.2), 1.1 and 2.0 (mean 1.5) and 3.9 and 8.1 (mean 6.1), respectively. So far only a limited number of clinical studies has been published including studies of acute stroke, multiple sclerosis and Alzheimer's disease...

  8. Guinea pig ascorbate status predicts tetrahydrobiopterin plasma concentration and oxidation ratio in vivo.

    Science.gov (United States)

    Mortensen, Alan; Hasselholt, Stine; Tveden-Nyborg, Pernille; Lykkesfeldt, Jens

    2013-10-01

    Tetrahydrobiopterin (BH₄) is an essential co-factor of nitric oxide synthases and is easily oxidized to dihydrobiopterin (BH₂) which promotes endothelial nitric oxide synthase uncoupling and deleterious superoxide production. Vitamin C has been shown to improve endothelial function by different mechanisms, some involving BH₄. The hypothesis of the present study was that vitamin C status, in particular low levels, influences biopterin redox status in vivo. Like humans, the guinea pig lacks the ability to synthesize vitamin C and was therefore used as model. Seven day old animals (n = 10/group) were given a diet containing 100, 250, 500, 750, 1000, or 1500 ppm vitamin C until euthanasia at age 60-64 days. Blood samples were drawn from the heart and analyzed for ascorbate, dehydroascorbic acid (DHA), BH₄ and BH₂ by high-performance liquid chromatography. Plasma BH₄ levels were found to be significantly lower in animals fed 100 ppm vitamin C compared to all other groups (P < .05 or less). BH₂ levels were not significantly different between groups but the BH₂-to-BH₄ ratio was higher in the group fed 100 ppm vitamin C (P < .001 all cases). Significant positive correlations between BH4 and ascorbate and between BH₂-to-BH₄ ratio and DHA were observed (P < .0001 both cases). Likewise, BH₂-to-BH₄ ratio was negatively correlated with ascorbate (P < .0001) as was BH₄ and DHA (P < .005). In conclusion, the redox status of plasma biopterins, essentially involved in vasodilation, depends on the vitamin C status in vivo. Thus, ingestion of insufficient quantities of vitamin C not only leads to vitamin C deficiency but also to increased BH₄ oxidation which may promote endothelial dysfunction. © 2013 Elsevier Inc. All rights reserved.

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

    International Nuclear Information System (INIS)

    Polishchuk, A.V.; Karaseva, E.T.; Korpela, T.; Karasev, V.E.

    2008-01-01

    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 2 O

  10. Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Abraham, J.L.; Thakral, C.; Skov, L.

    2008-01-01

    patients with NSF and to determine their relative concentrations over time from administration of GBMCA. Methods An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with gadodiamide-related NSF and one NSF-negative gadodiamide-exposed dialysis patient, ranging from 16...... days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. Results We detected Gd in skin lesions of all...... contained phosphorus, calcium and sodium. The ratio of Gd to calcium in tissue deposits correlated positively with the gadodiamide dose and with serum ionized calcium at the time of Gd exposure. Conclusions These findings demonstrate the in vivo release (through transmetallation) of the toxic free Gd3+ from...

  11. Fluoroquinolone-gyrase-DNA complexes: two modes of drug binding.

    Science.gov (United States)

    Mustaev, Arkady; Malik, Muhammad; Zhao, Xilin; Kurepina, Natalia; Luan, Gan; Oppegard, Lisa M; Hiasa, Hiroshi; Marks, Kevin R; Kerns, Robert J; Berger, James M; Drlica, Karl

    2014-05-02

    DNA gyrase and topoisomerase IV control bacterial DNA topology by breaking DNA, passing duplex DNA through the break, and then resealing the break. This process is subject to reversible corruption by fluoroquinolones, antibacterials that form drug-enzyme-DNA complexes in which the DNA is broken. The complexes, called cleaved complexes because of the presence of DNA breaks, have been crystallized and found to have the fluoroquinolone C-7 ring system facing the GyrB/ParE subunits. As expected from x-ray crystallography, a thiol-reactive, C-7-modified chloroacetyl derivative of ciprofloxacin (Cip-AcCl) formed cross-linked cleaved complexes with mutant GyrB-Cys(466) gyrase as evidenced by resistance to reversal by both EDTA and thermal treatments. Surprisingly, cross-linking was also readily seen with complexes formed by mutant GyrA-G81C gyrase, thereby revealing a novel drug-gyrase interaction not observed in crystal structures. The cross-link between fluoroquinolone and GyrA-G81C gyrase correlated with exceptional bacteriostatic activity for Cip-AcCl with a quinolone-resistant GyrA-G81C variant of Escherichia coli and its Mycobacterium smegmatis equivalent (GyrA-G89C). Cip-AcCl-mediated, irreversible inhibition of DNA replication provided further evidence for a GyrA-drug cross-link. Collectively these data establish the existence of interactions between the fluoroquinolone C-7 ring and both GyrA and GyrB. Because the GyrA-Gly(81) and GyrB-Glu(466) residues are far apart (17 Å) in the crystal structure of cleaved complexes, two modes of quinolone binding must exist. The presence of two binding modes raises the possibility that multiple quinolone-enzyme-DNA complexes can form, a discovery that opens new avenues for exploring and exploiting relationships between drug structure and activity with type II DNA topoisomerases.

  12. Stability Prediction of Polymeric Suspensions of some Fluoroquinolones

    OpenAIRE

    Subhashree Sahoo; Chandra Kanti Chakraborti; Pradipta Kumar Behera

    2014-01-01

    Considering the importance of physical stability, zeta potential values, percentage volume of sedimentation and redispersibility of polymeric suspensions of some fluoroquinolones like Ciprofloxacin (Cipro) and Ofloxacin (Oflox) were measured. These formulations were prepared using two grades of Carbopol polymer such as C934 and C940; and Hydroxypropyl methylcellulose (HPMC). Above mentioned values of each suspension was determined by following standard methods. The results of those experiment...

  13. In vivo characterization of a smart MRI agent that displays an inverse response to calcium concentration.

    Science.gov (United States)

    Mamedov, Ilgar; Canals, Santiago; Henig, Jörg; Beyerlein, Michael; Murayama, Yusuke; Mayer, Hermann A; Logothetis, Nikos K; Angelovski, Goran

    2010-12-15

    Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd(3+) complex linked to an aminobis(methylenephosphonate) group for chelating Ca(2+) was synthesized and investigated. The longitudinal relaxivity (r(1)) of this complex decreases during the relaxometric titration with Ca(2+) from 5.76 to 3.57 mM(-1) s(-1) upon saturation. The r(1) is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu(3+) complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA).

  14. Ascorbate concentrations in vitro and in vivo, and their role in the radiation response of cells

    International Nuclear Information System (INIS)

    Stratford, M.R.L.; Hodgkiss, R.J.

    1985-01-01

    Hydrogen-atom or electron-transfer reactions of ascorbate are often invoked in discussing its potential role in radiobiology and free radical damage by cytotoxins, but detailed information on actual levels in experimental systems is lacking. A range of 0-250 μM ascorbate is present in several commonly used mammalian cell culture media. V79 379A Chinese hamster cells can concentrate ascorbate from medium containing 200 or 500 μM ascorbate but when ascorbate is absent in medium, cells do not appear to contain a significant amount. Tumour concentrations are approximately 1mM, similar to that of glutathione (GSH). There is much current interest in depleting cells of GSH to enhance radiosensitivity, and ascorbate is maintained by a GSH dependent enzyme, glutathione dehydrogenase. Data is presented on the effect of GSH depletion by buthionine sulphoximine on cell and tumour ascorbate levels, and the effect of ascorbate on in vitro radiosensitivity, and misonidazole sensitizing efficiency

  15. Red blood cell 2,3-diphosphoglycerate concentration and in vivo P50 during early critical illness.

    Science.gov (United States)

    Ibrahim, Ezz el din S; McLellan, Stuart A; Walsh, Timothy S

    2005-10-01

    To measure red blood cell 2,3-diphosphoglycerate (RBC 2,3-DPG) concentrations in early critical illness; to investigate factors associated with high or low RBC 2,3-DPG levels; to calculate in vivo P50 in patients with early critical illness; and to explore the relationship between RBC 2,3-DPG and intensive care mortality. Prospective cohort study. General medical-surgical intensive care unit (ICU) of a major Scottish teaching hospital. One-hundred eleven critically ill patients during the first 24 hrs in the ICU with no history of chronic hematologic disorders or RBC transfusion within 24 hrs and 34 age- and sex-matched healthy reference subjects. None. We measured RBC 2,3-DPG concentration, plasma biochemistry values, and arterial blood gas parameters. On average, RBC 2,3-DPG was lower among critically ill patients than controls (mean [sd], 14.1 [6.3] vs. 16.7 [3.7] mumol/g hemoglobin; p = .004) and had a wider range of values (patients, 3.2-32.5 mumol/g hemoglobin; reference group, 9.1-24.3). Regression analysis indicated a strong independent association between plasma pH and RBC 2,3-DPG (B, 32.15 [95% confidence interval, 19.07-46.22], p level was normal (3.8 kPa) but varied widely among patients (range, 2.0-5.5 kPa). RBC 2,3-DPG concentration was similar for ICU survivors and nonsurvivors. RBC 2,3-DPG concentrations vary widely among critically ill patients. Acidosis is associated with lower RBC 2,3-DPG concentrations, but anemia is not associated with a compensatory increase in RBC 2,3-DPG early in critical illness. Lower RBC 2,3-DPG concentrations during the first 24 hrs of intensive care are not associated with higher ICU mortality.

  16. Effect of albumin and dextrose concentration on ultrasound and microbubble mediated gene transfection in vivo.

    Science.gov (United States)

    Browning, Richard J; Mulvana, Helen; Tang, Meng-Xing; Hajnal, Jo V; Wells, Dominic J; Eckersley, Robert J

    2012-06-01

    Ultrasound and microbubble mediated gene transfection has great potential for site-selective, safe gene delivery. Albumin-based microbubbles have shown the greatest transfection efficiency but have not been optimised specifically for this purpose. Additionally, few studies have highlighted desirable properties for transfection specific microbubbles. In this article, microbubbles were made with 2% or 5% (w/v) albumin and 20% or 40% (w/v) dextrose solutions, yielding four distinct bubble types. These were acoustically characterised and their efficiency in transfecting a luciferase plasmid (pGL4.13) into female, CD1 mice myocardia was measured. For either albumin concentration, increasing the dextrose concentration increased scattering, attenuation and resistance to ultrasound, resulting in significantly increased transfection. A significant interaction was noted between albumin and dextrose; 2% albumin bubbles made with 20% dextrose showed the least transfection but the most transfection with 40% dextrose. This trend was seen for both nonlinear scattering and attenuation behaviour but not for resistance to ultrasound or total scatter. We have determined that the attenuation behaviour is an important microbubble characteristic for effective gene transfection using ultrasound. Microbubble behaviour can also be simply controlled by altering the initial ingredients used during manufacture. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  17. Identification of benign and malignant thyroid nodules by in vivo iodine concentration measurement using single-source dual energy CT

    Science.gov (United States)

    Gao, Shun-Yu; Zhang, Xiao-Yan; Wei, Wei; Li, Xiao-Ting; Li, Yan-Ling; Xu, Min; Sun, Ying-Shi; Zhang, Xiao-Peng

    2016-01-01

    Abstract This study proposed to determine whether in vivo iodine concentration measurement by single-source dual energy (SSDE) CT can improve differentiation between benign and malignant thyroid nodules. In total, 53 patients presenting with thyroid nodules underwent SSDE CT scanning. Iodine concentrations were measured for each nodule and normal thyroid tissue using the GSI-viewer image analysis software. A total of 26 thyroid nodules were malignant in 26 patients and confirmed by surgery; 33 nodules from 27 patients were benign, with 10 confirmed by surgery and others after follow-up. Iodine concentrations with plain CT were significantly lower in malignant than benign nodules (0.47 ± 0.20 vs 1.17 ± 0.38 mg/mL, P = 0.00). Receiver operating characteristic (ROC) curve showed an area under the curve (AUC) of 0.93; with a cutoff of 0.67, iodine concentration showed 92.3% sensitivity and 88.5% specificity in diagnosing malignancy. Iodine concentration obtained by enhanced and plain CT were significantly higher in malignant than benign nodules (9.05 ± 3.35 vs 3.46 ± 2.24 mg/mL, P = 0.00). ROC curve analysis showed an AUC of 0.93; with a cutoff value of 3.37, iodine concentration displayed 78% sensitivity, 95% specificity in diagnosing malignancy. Combining unenhanced with enhanced iodine concentrations, the diagnostic equation was: Y = –8.641 × unenhanced iodine concentration + 0.663 × iodine concentration. ROC curve showed an AUC of 0.98 (95% CI, 0.94, 1.00). With Y ≥ –2 considered malignancy, diagnostic sensitivity and specificity were 96%, 96.3%, respectively. This study concluded that SSDE CT can detect the differences in iodine uptake and blood supply between benign and malignant thyroid lesions. PMID:27684811

  18. In vitro and in vivo physiology of low nanomolar concentrations of Zn2+ in artificial cerebrospinal fluid.

    Science.gov (United States)

    Tamano, Haruna; Nishio, Ryusuke; Shakushi, Yukina; Sasaki, Miku; Koike, Yuta; Osawa, Misa; Takeda, Atsushi

    2017-02-17

    Artificial cerebrospinal fluid (ACSF), i.e., brain extracellular medium, which includes Ca 2+ and Mg 2+ , but not other divalent cations such as Zn 2+ , has been used for in vitro and in vivo experiments. The present study deals with the physiological significance of extracellular Zn 2+ in ACSF. Spontaneous presynaptic activity is suppressed in the stratum lucidum of brain slices from young rats bathed in ACSF containing 10 nM ZnCl 2 , indicating that extracellular Zn 2+ modifies hippocampal presynaptic activity. To examine the in vivo action of 10 nM ZnCl 2 on long-term potentiation (LTP), the recording region was perfused using a recording electrode attached to a microdialysis probe. The magnitude of LTP was not modified in young rats by perfusion with ACSF containing 10 nM ZnCl 2 , compared to perfusion with ACSF without Zn 2+ , but attenuated by perfusion with ACSF containing 100 nM ZnCl 2 . Interestingly, the magnitude of LTP was not modified in aged rats even by perfusion with ACSF containing 100 nM ZnCl 2 , but enhanced by perfusion with ACSF containing 10 mM CaEDTA, an extracellular Zn 2+ chelator. The present study indicates that the basal levels of extracellular Zn 2+ , which are in the range of low nanomolar concentrations, are critical for synaptic activity and perhaps increased age-dependently.

  19. DNA repair inhibition by UVA photoactivated fluoroquinolones and vemurafenib

    Science.gov (United States)

    Peacock, Matthew; Brem, Reto; Macpherson, Peter; Karran, Peter

    2014-01-01

    Cutaneous photosensitization is a common side effect of drug treatment and can be associated with an increased skin cancer risk. The immunosuppressant azathioprine, the fluoroquinolone antibiotics and vemurafenib—a BRAF inhibitor used to treat metastatic melanoma—are all recognized clinical photosensitizers. We have compared the effects of UVA radiation on cultured human cells treated with 6-thioguanine (6-TG, a DNA-embedded azathioprine surrogate), the fluoroquinolones ciprofloxacin and ofloxacin and vemurafenib. Despite widely different structures and modes of action, each of these drugs potentiated UVA cytotoxicity. UVA photoactivation of 6-TG, ciprofloxacin and ofloxacin was associated with the generation of singlet oxygen that caused extensive protein oxidation. In particular, these treatments were associated with damage to DNA repair proteins that reduced the efficiency of nucleotide excision repair. Although vemurafenib was also highly phototoxic to cultured cells, its effects were less dependent on singlet oxygen. Highly toxic combinations of vemurafenib and UVA caused little protein carbonylation but were nevertheless inhibitory to nucleotide excision repair. Thus, for three different classes of drugs, photosensitization by at least two distinct mechanisms is associated with reduced protection against potentially mutagenic and carcinogenic DNA damage. PMID:25414333

  20. Toxicity of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin to photoautotrophic aquatic organisms.

    Science.gov (United States)

    Ebert, Ina; Bachmann, Jean; Kühnen, Ute; Küster, Anette; Kussatz, Carola; Maletzki, Dirk; Schlüter, Christoph

    2011-12-01

    The present study investigated the growth inhibition effect of the fluoroquinolone antibiotics enrofloxacin and ciprofloxacin on four photoautotrophic aquatic species: the freshwater microalga Desmodesmus subspicatus, the cyanobacterium Anabaena flos-aquae, the monocotyledonous macrophyte Lemna minor, and the dicotyledonous macrophyte Myriophyllum spicatum. Both antibiotics, which act by inhibiting the bacterial DNA gyrase, demonstrated high toxicity to A. flos-aquae and L. minor and moderate to slight toxicity to D. subspicatus and M. spicatum. The cyanobacterium was the most sensitive species with median effective concentration (EC50) values of 173 and 10.2 µg/L for enrofloxacin and ciprofloxacin, respectively. Lemna minor proved to be similarly sensitive, with EC50 values of 107 and 62.5 µg/L for enrofloxacin and ciprofloxacin, respectively. While enrofloxacin was more toxic to green algae, ciprofloxacin was more toxic to cyanobacteria. Calculated EC50s for D. subspicatus were 5,568 µg/L and >8,042 µg/L for enrofloxacin and ciprofloxacin, respectively. These data, as well as effect data from the literature, were compared with predicted and reported environmental concentrations. For two of the four species, a risk was identified at ciprofloxacin concentrations found in surface waters, sewage treatment plant influents and effluents, as well as in hospital effluents. For ciprofloxacin the results of the present study indicate a risk even at the predicted environmental concentration. In contrast, for enrofloxacin no risk was identified at predicted and measured concentrations. Copyright © 2011 SETAC.

  1. Effect of exercise on erythrocyte count and blood activity concentration after technetium-99m in vivo red blood cell labeling

    International Nuclear Information System (INIS)

    Konstom, M.A.; Tu'meh, S.; Wynne, J.; Beck, J.R.; Kozlowski, J.; Holman, B.L.

    1982-01-01

    The effects of exercise on blood radiotracer concentration after technetium-99m in vivo red blood cell labeling was studied. After red blood cell labeling, 13 subjects underwent maximal supine bicycle exercise. Radioactivity, analyzed with a well counter, was measured in heparinized venous blood samples drawn at rest and during peak exercise. Changes in activity were compared with changes in erythrocyte count. Activity and erythrocyte counts increased in erythrocyte count (r=0.78), but did not correlate with either duration of exercise or maximal heart rate. Twenty minutes after termination of exercise, activity and erythrocyte count had decreased from peak exercise values but remained higher than preexercise values. In nine nonexercised control subjects, samples drawn 20 minutes apart showed no change in activity or in erythrocyte count. It was concluded that exercise increases blood activity, primarily because of an increase in erythrocyte count. During radionuclide ventriculography, blood activity must be measured before and after any intervention, particularly exercise, before a change in left ventricular activity can be attributed to a change in left ventricular volume

  2. Early postoperative fluoroquinolone use is associated with an increased revision rate after arthroscopic rotator cuff repair.

    Science.gov (United States)

    Cancienne, Jourdan M; Brockmeier, Stephen F; Rodeo, Scott A; Young, Chris; Werner, Brian C

    2017-07-01

    To evaluate the association of postoperative fluoroquinolone use following arthroscopic primary rotator cuff repair with failure requiring revision rotator cuff repair. An insurance database was queried for patients undergoing rotator cuff repair from 2007 to 2015. These patients were divided into three groups: (1) patients prescribed fluoroquinolones within 6 months postoperatively (divided into 0-2, 2-4, and 4-6 months), (2) a matched negative control cohort of patients not prescribed fluoroquinolones, and (3) a matched positive control cohort of patients prescribed fluoroquinolones between 6 and 18 months following rotator cuff repair. Rates of failure requiring revision rotator cuff repair were compared within 2 years. A total of 1292 patients were prescribed fluoroquinolones within 6 months after rotator cuff repair, including 442 within 2 months, 433 within 2 to 4 months, and 417 within 4 to 6 months, and were compared to 5225 matched negative controls and 1597 matched positive controls. The rate of revision rotator cuff repair was significantly higher in patients prescribed fluoroquinolones within 2 months (6.1 %) compared to matched negative (2.2 %, P = 0.0009) and positive controls (2.4 %, P = 0.0026). There were no significant differences in the rate of revision rotator cuff repair when fluoroquinolones were prescribed >2 months after rotator cuff repair. Early use of fluoroquinolones following rotator cuff repair was independently associated with significantly increased rates of failure requiring revision rotator cuff repair. This is the first clinical study examining the association of postoperative fluoroquinolone use with failure following arthroscopic rotator cuff repair. III.

  3. Mechanism for translocation of fluoroquinolones across lipid membranes

    DEFF Research Database (Denmark)

    Cramariuc, O.; Rog, T.; Javanainen, M.

    2012-01-01

    Classical atom-scale molecular dynamics simulations, constrained free energy calculations, and quantum mechanical (QM) calculations are employed to study the diffusive translocation of ciprofloxacin (CPFX) across lipid membranes. CPFX is considered here as a representative of the fluoroquinolone...... antibiotics class. Neutral and zwitterionic CPFX coexist at physiological pH, with the latter being predominant. Simulations reveal that only the neutral form permeates the bilayer, and it does so through a novel mechanism that involves dissolution of concerted stacks of zwitterionic ciprofloxacins....... Subsequent QM analysis of the observed molecular stacking shows the important role of partial charge neutralization in the stacks, highlighting how the zwitterionic form of the drug is neutralized for translocation. The findings propose a translocation mechanism in which zwitterionic CPFX molecules approach...

  4. Enhanced resistance to fluoroquinolones in laboratory-grown mutants & clinical isolates of Shigella due to synergism between efflux pump expression & mutations in quinolone resistance determining region

    Directory of Open Access Journals (Sweden)

    Neelam Taneja

    2015-01-01

    Full Text Available Background & objectives: There is a worldwide emergence of fluoroquinolone resistance in Shigella species. To understand the molecular mechanisms associated with fluoroquinolone resistance, naturally occurring fluoroquinolone-resistant strains and laboratory-induced spontaneous mutants of Shigella spp. were used and the relative contributions of acrAB-tolC efflux pumps, gyrase and topoisomerase target gene mutations towards fluoroquinolone resistance were determined. Methods: Eight Shigella flexneri and six S. dysenteriae clinical isolates were studied. Three consecutive mutants resistant to ciprofloxacin for S. flexneri SFM1 (≥0.25 µg/ml, SFM2 (≥4 µg/ml and SFM3 (≥32 µg/ml were selected in 15 steps from susceptible isolates by serial exposure to increasing concentrations of nalidixic acid and ciprofloxacin. Similarly, two mutants for S. dysenteriae SDM1 (≥0.25 µg/ml and SDM2 (≥4 µg/ml were selected in eight steps. After PCR amplification sequence analyses of gyrase and topoisomerase target genes were performed. Expression of efflux genes acrA, acrB, acrR and tolC was measured using real-time PCR. Results: Mutations were observed in gyrA Ser [83]→Leu, Asp [87]→Asn/Gly, Val [196]→Ala and in parC Phe [93]→Val, Ser [80]→Ile, Asp [101]→Glu and Asp [110]→Glu. Overall, acrA and acrB overexpression was associated with fluoroquinolone resistance ( p0 <0.05; while tolC and acrR expression levels did not. Interpretation & conclusions: Fluoroquinolone resistance in Shigella spp. is the end product of either a single or a combination of mutations in QRDRs and/ or efflux activity. Novel polymorphisms were observed at Val [196]→Ala in gyrA in clinical isolates and Phe [93]→Val, Asp [101]→Glu, Asp [110]→Glu and in parC in majority of laboratory-grown mutants.

  5. The role of gyrA and parC mutations in fluoroquinolones-resistant Pseudomonas aeruginosa isolates from Iran

    Directory of Open Access Journals (Sweden)

    Roghayeh Nouri

    Full Text Available Abstract The aim of this study was to examine mutations in the quinolone-resistance-determining region (QRDR of gyrA and parC genes in Pseudomonas aeruginosa isolates. A total of 100 clinical P. aeruginosa isolates were collected from different university-affiliated hospitals in Tabriz, Iran. Minimum inhibitory concentrations (MICs of ciprofloxacin and levofloxacin were evaluated by agar dilution assay. DNA sequences of the QRDR of gyrA and parC were determined by the dideoxy chain termination method. Of the total 100 isolates, 64 were resistant to ciprofloxacin. No amino acid alterations were detected in gyrA or parC genes of the ciprofloxacin susceptible or ciprofloxacin intermediate isolates. Thr-83 → Ile substitution in gyrA was found in all 64 ciprofloxacin resistant isolates. Forty-four (68.75% of them had additional substitution in parC. A correlation was found between the number of the amino acid alterations in the QRDR of gyrA and parC and the level of ciprofloxacin and levofloxacin resistance of the P. aeruginosa isolates. Ala-88 → Pro alteration in parC was generally found in high level ciprofloxacin resistant isolates, which were suggested to be responsible for fluoroquinolone resistance. These findings showed that in P. aeruginosa, gyrA was the primary target for fluoroquinolone and additional mutation in parC led to highly resistant isolates.

  6. Phenotypic and genotypic evaluation of fluoroquinolone resistance in clinical isolates of Staphylococcus aureus in Tehran.

    Science.gov (United States)

    Aligholi, Marzieh; Mirsalehian, Akbar; Halimi, Shahnaz; Imaneini, Hossein; Taherikalani, Morovat; Jabalameli, Fereshteh; Asadollahi, Parisa; Mohajer, Babak; Abdollahi, Alireza; Emaneini, Mohammad

    2011-09-01

    Fluoroquinolones are broad-spectrum antibiotics widely used in the treatment of bacterial infections such as Staphylococcus aureus isolates. Resistance to these antibiotics is increasing. The occurrence of mutations in the grlA and gyrA loci were evaluated in 69 fluoroquinolone-resistant S. aureus isolates from 2 teaching hospitals of Tehran University of Medical Sciences. Out of the 165 S. aureus isolates, 87 (52.7%) were resistant to methicillin and 69 (41.8%) were resistant to fluoroquinolone. Fluoroquinolone-resistant S. aureus isolates had a mutation at codon 80 in the grlA gene and different mutational combinations in the gyrA gene. These mutational combinations included 45 isolates at codons 84 and 86, 23 isolates at codons 84, 86 and 106 and 1 isolate at codons 84, 86 and 90. Fluoroquinolone-resistant S. aureus isolates were clustered into 33 PFGE types. The findings of this study show that the fluoroquinolone-resistant S. aureus strains isolated in the teaching hospitals in Tehran had multiple mutations in the QRDRs region of both grlA and gyrA genes.

  7. Comparison of contamination rates between preserved and preservative-free fluoroquinolone eyedrops.

    Science.gov (United States)

    Kim, Mo Sae; Kim, Hong Kyun; Kim, Joon Mo; Choi, Chul Young

    2013-03-01

    To evaluate the antimicrobial effectiveness of preservative-free fluoroquinolone products compared with benzalkonium chloride containing fluoroquinolones using the challenge test provided by the United States Pharmacopeia (USP) and the in-use test. 1. Challenge test: to compare the growth of microorganisms between different fluoroquinolone preparations, four test organisms, including Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger were chosen among five microorganisms listed by USP 2004. The inoculated products were sampled for microbial survivors at days 7, 14, and 28 following initial inoculation at room temperature. The number of surviving organisms were calculated as a Log10 reduction from the original inocula. 2. In-use test: a total of 100 bottles were collected after instillation of preservative-free fluoroquinolone eyedrops in volunteer patients after 1 week of use. The remaining fluid and tips of the bottles were cultured. Colonies on the plates were counted at the end of the incubation period. All microorganisms were identified by Gram staining and biochemical assays. 1. Challenge test: preservative-free gatifloxacin and levofloxacin demonstrated a lower log reduction against A. niger than preserved fluoroquinolones and preservative-free moxifloxacin at all time points. 2. In-use test: There was no contamination identified on plates inoculated by preservative-free quinolone bottles after 1 week of use in this study. Physicians should be aware of the lower antifungal preservative effectiveness of some preservative-free fluoroquinolone preparations than preserved ones.

  8. Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities

    Directory of Open Access Journals (Sweden)

    Temilolu Idowu

    2017-11-01

    Full Text Available Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV, leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds.

  9. Swept source optical coherence tomography for in vivo growth monitoring of capsicum annuum seeds treated with different NaCl concentrations

    Science.gov (United States)

    Ravichandran, Naresh Kumar; Wijesinghe, Ruchire Eranga; Lee, Seung-Yeol; Shirazi, Muhammad Faizan; Park, Kibeom; Jung, Hee-Young; Jeon, Mansik; Kim, Jeehyun

    2017-04-01

    In this study, Optical coherence tomography (OCT) is demonstrated as a plausible optical tool for in vivo detection of plant seeds and its morphological changes during growth. The experiment was carried out on Capsicum annuum seeds that were treated with different molar concentrations of NaCl to investigate the most optimal concentration for the seed growth. The monitoring process was carried out for 9 consecutive days. The in vivo 2D OCT images of the treated seeds were obtained and compared with seeds that were grown with sterile distilled water. The obtained results confirm the feasibility of using OCT for the proposed application. Normalized A-scan analysis method is utilized for supporting the concluded results.

  10. Decreased 2,3-diphosphoglycerate concentration in low cardiac output patients and its influence on the determination of in vivo p50.

    Science.gov (United States)

    Piccioni, Marilde A; Cestari, Idágene A; Strunz, Célia M C; Auler, José O

    2003-08-01

    We investigated whether 2,3-diphosphoglycerate (2,3-DPG) is altered in patients with low cardiac output and the influence of its concentration on the calculation of in vivo P(50). Biochemical and blood gas analysis were performed along with the measurement of cardiac output and body temperature in 13 patients submitted to cardiopulmonary bypass surgeries without the use of donor blood. In vivo P(50) was calculated using the measured (P(50m)) and the estimated 2,3-DPG (P(50e)). 2,3-DPG concentration was lower in these patients when compared to the values obtained in normal volunteers (6.9 +/- 2.2 vs. 11.9 +/- 2.4 microm/gHb). P(50m) was lower than P(50e) (21.6 +/- 1.1 vs. 30.1 +/- 1.2 mm Hg) at all time points. Our data show that in patients with low cardiac output, 2,3-DPG concentration is reduced. Therefore, in these patients, the use of standard values for this variable may introduce an error in the calculation of in vivo P(50).

  11. Impact of fluoroquinolone treatment on delay of tuberculosis diagnosis: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Catherine A Hogan

    2017-01-01

    Full Text Available Background: Fluoroquinolones are among the most commonly used antibiotics for the treatment of respiratory infections. Because fluoroquinolones show bactericidal activity against Mycobacterium tuberculosis, there is concern that their use can delay the diagnosis of tuberculosis. We conducted a systematic review and meta-analysis to assess whether empiric treatment with fluoroquinolones delays the diagnosis and treatment of tuberculosis in patients with respiratory tract infections. Objectives: The primary objective was to assess the delay in days in the diagnosis and treatment of tuberculosis, among patients who received quinolones, compared to those who received non-fluoroquinolone antibiotics. Methods: We included studies of adult patients treated with fluoroquinolones prior to a confirmed diagnosis of tuberculosis. We performed a literature search of 7 databases (including PubMed, Embase and Cochrane Library with no language restrictions. We calculated an unweighted mean of estimate of difference in delay across all studies. For the studies for which the estimate was available as a mean with standard deviation, a weighted average using a random effects meta-analysis model was estimated. Results: A total of 3983 citations were identified from the literature search; of these, 17 articles were selected for full-text review. A total of 10 studies were retained for the synthesis. These included 7 retrospective cohort studies and 3 case-control studies. Only one of these studies was from a high TB burden country, South Africa. The most commonly used fluoroquinolones were levofloxacin, gemifloxacin and moxifloxacin. The unweighted average of difference in delay between the fluoroquinolone group and non-fluoroquinolone group was 12.9 days (95% CI 6.1–19.7. When these differences were pooled using a random effects model, the weighted estimate was 10.9 days (95% CI 4.2–17.6. When stratified by acid-fast smear status, the delay was

  12. Quantitative determination of localized tissue oxygen concentration in vivo by two-photon excitation phosphorescence lifetime measurements

    NARCIS (Netherlands)

    Mik, Egbert G.; van Leeuwen, Ton G.; Raat, Nicolaas J.; Ince, Can

    2004-01-01

    This study describes the use of two-photon excitation phosphorescence lifetime measurements for quantitative oxygen determination in vivo. Doubling the excitation wavelength of Pd-porphyrin from visible light to the infrared allows for deeper tissue penetration and a more precise and confined

  13. Induction of prophages by fluoroquinolones in Streptococcus pneumoniae: implications for emergence of resistance in genetically-related clones.

    Directory of Open Access Journals (Sweden)

    Elena López

    Full Text Available Antibiotic resistance in Streptococcus pneumoniae has increased worldwide by the spread of a few clones. Fluoroquinolone resistance occurs mainly by alteration of their intracellular targets, the type II DNA topoisomerases, which is acquired either by point mutation or by recombination. Increase in fluoroquinolone-resistance may depend on the balance between antibiotic consumption and the cost that resistance imposes to bacterial fitness. In addition, pneumococcal prophages could play an important role. Prophage induction by fluoroquinolones was confirmed in 4 clinical isolates by using Southern blot hybridization. Clinical isolates (105 fluoroquinolone-resistant and 160 fluoroquinolone-susceptible were tested for lysogeny by using a PCR assay and functional prophage carriage was studied by mitomycin C induction. Fluoroquinolone-resistant strains harbored fewer inducible prophages (17/43 than fluoroquinolone-susceptible strains (49/70 (P = 0.0018. In addition, isolates of clones associated with fluoroquinolone resistance [CC156 (3/25; CC63 (2/20, and CC81 (1/19], had lower frequency of functional prophages than isolates of clones with low incidence of fluoroquinolone resistance [CC30 (4/21, CC230 (5/20, CC62 (9/21, and CC180 (21/30]. Likewise, persistent strains from patients with chronic respiratory diseases subjected to fluoroquinolone treatment had a low frequency of inducible prophages (1/11. Development of ciprofloxacin resistance was tested with two isogenic strains, one lysogenic and the other non-lysogenic: emergence of resistance was only observed in the non-lysogenic strain. These results are compatible with the lysis of lysogenic isolates receiving fluoroquinolones before the development of resistance and explain the inverse relation between presence of inducible prophages and fluoroquinolone-resistance.

  14. Variability of in vivo recovery of factor IX after infusion of monoclonal antibody purified factor IX concentrates in patients with hemophilia B. The Mononine Study Group.

    Science.gov (United States)

    White, G C; Shapiro, A D; Kurczynski, E M; Kim, H C; Bergman, G E

    1995-05-01

    Monoclonal antibody purified factor IX concentrate, Mononine (Armour Pharmaceutical Company, Kankakee, Illinois, USA), is a recently developed replacement factor concentrate for the treatment of patients with hemophilia B. The pharmacokinetic properties of monoclonal antibody purified factor IX concentrate (MAb Factor IX concentrate) have been evaluated in only small samples of patients, and little is known about those factors that might influenced in vivo recovery of factor IX after infusion is a larger patient population. In vivo recovery of factor IX was therefore evaluated for 80 different indications in 72 patients who received MAb Factor IX concentrate for the management of spontaneous or trauma-induced bleeding, or as prophylaxis with surgery. The average recovery after infusions for presurgical pharmacokinetic analysis (mean +/- standard deviation) was 1.28 +/- 0.56 U/dl rise per U/kg infused (range 0.41-2.80), and the average recovery after all infusions for treatment was 1.23 +/- 0.49 U/dl rise per U/kg infused (range - 0.35-2.92). Recovery values for multiple MAb Factor IX doses in a given patient were also variable; the average recovery was 1.22 +/- 0.53 U/dl rise per U/kg given, and standard deviations ranged from 0.03 to 1.26. Patient age, weight, and MAb Factor IX concentrate dose minimally but significantly influenced factor IX recovery. There was no significant effect of either race, history of previous thrombotic complications during treatment with other replacement factor concentrates, or bleeding state on recovery. All of the patients treated with this preparation experienced excellent hemostasis, and no thrombotic complications were observed.

  15. Degradation of fluoroquinolone antibiotics during ionizing radiation treatment and assessment of antibacterial activity, toxicity and biodegradability of the products

    Science.gov (United States)

    Tegze, Anna; Sági, Gyuri; Kovács, Krisztina; Homlok, Renáta; Tóth, Tünde; Mohácsi-Farkas, Csilla; Wojnárovits, László; Takács, Erzsébet

    2018-06-01

    This work aimed at investigating the ionizing radiation induced degradation of two fluoroquinolone antibiotics: norfloxacin and ciprofloxacin. At 0.1 mmol dm-3 concentration a low dose, 2 kGy was sufficient to degrade the initial molecules. However, despite of the high removal efficiency the degrees of both the mineralization and the oxidation were low, ∼10% and ∼25%, respectively. (The difference between the results obtained in norfloxacin and ciprofloxacin solutions was not statistically significant.) Broth microdilution tests carried out on Staphylococcus aureus evidenced removal of antibacterial activity in samples irradiated with 2 kGy. Acute toxicity determined on Vibrio fischeri bacteria showed increased toxicity at low doses indicating that the early degradation products were more toxic than the initial molecules. The results of biodegradation experiments performed in activated sludge have shown that the degradation products have become available to the metabolic processes of the microorganisms.

  16. Focus on JNJ-Q2, a novel fluoroquinolone, for the management of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections

    Directory of Open Access Journals (Sweden)

    Jones TM

    2016-06-01

    Full Text Available Travis M Jones,1,2 Steven W Johnson,1,3 V Paul DiMondi,1,4 Dustin T Wilson,1,2 1Department of Pharmacy Practice, College of Pharmacy and Health Sciences, Campbell University, Buies Creek, 2Department of Pharmacy, Duke University Hospital, Durham, 3Department of Pharmacy, Forsyth Medical Center, Novant Health, Winston-Salem, 4Department of Pharmacy, Durham VA Medical Center, Durham, NC, USA Abstract: JNJ-Q2 is a novel, fifth-generation fluoroquinolone that has excellent in vitro and in vivo activity against a variety of Gram-positive and Gram-negative organisms. In vitro studies indicate that JNJ-Q2 has potent activity against pathogens responsible for acute bacterial skin and skin structure infections (ABSSSI and community-acquired bacterial pneumonia (CABP, such as Staphylococcus aureus and Streptococcus pneumoniae. JNJ-Q2 also has been shown to have a higher barrier to resistance compared to other agents in the class and it remains highly active against drug-resistant organisms, including methicillin-resistant S. aureus, ciprofloxacin-resistant methicillin-resistant S. aureus, and drug-resistant S. pneumoniae. In two Phase II studies, the efficacy of JNJ-Q2 was comparable to linezolid for ABSSSI and moxifloxacin for CABP. Furthermore, JNJ-Q2 was well tolerated, with adverse event rates similar to or less than other fluoroquinolones. With an expanded spectrum of activity and low potential for resistance, JNJ-Q2 shows promise as an effective treatment option for ABSSSI and CABP. Considering its early stage of development, the definitive role of JNJ-Q2 against these infections and its safety profile will be determined in future Phase III studies. Keywords: JNJ-Q2, fluoroquinolone, ABSSSI, CABP, MRSA

  17. Effects of nonstructural carbohydrates and protein sources on intake, apparent total tract digestibility, and ruminal metabolism in vivo and in vitro with high-concentrate beef cattle diets.

    Science.gov (United States)

    Rotger, A; Ferret, A; Calsamiglia, S; Manteca, X

    2006-05-01

    To investigate the effects of synchronizing nonstructural carbohydrate (NSC) and protein degradation on intake and rumen microbial fermentation, four ruminally fistulated Holstein heifers (BW = 132.3 +/- 1.61 kg) fed high-concentrate diets were assigned to a 4 x 4 Latin square design with a 2 x 2 factorial arrangement of treatments studied in vivo and in vitro with a dual-flow continuous culture system. Two NSC sources (barley and corn) and 2 protein sources [soybean meal (SBM) and sunflower meal (SFM)] differing in their rate and extent of ruminal degradation were combined resulting in a synchronized rapid fermentation diet (barley-SFM), a synchronized slow fermentation diet (corn-SBM), and 2 unsynchronized diets with a rapidly and a slowly fermenting component (barley-SBM, and corn-SFM). In vitro, the fermentation profile was studied at a constant pH of 6.2, and at a variable pH with 12 h at pH 6.4 and 12 h at pH 5.8. Synchronization tended to result in greater true OM digestion (P = 0.072), VFA concentration (P = 0.067), and microbial N flow (P = 0.092) in vitro, but had no effects on in vivo fermentation pattern or on apparent total tract digestibility. The NSC source affected the efficiency of microbial protein synthesis in vitro, tending to be greater (P = 0.07) for barley-based diets, and in vivo, the NSC source tended to affect intake. Dry matter and OM intake tended to be greater (P > or = 0.06) for corn- than barley-based diets. Ammonia N concentration was lower in vitro (P = 0.006) and tended to be lower in vivo (P = 0.07) for corn- than barley-based diets. In vitro, pH could be reduced from 6.4 to 5.8 for 12 h/d without any effect on ruminal fermentation or microbial protein synthesis. In summary, ruminal synchronization seemed to have positive effects on in vitro fermentation, but in vivo recycling of endogenous N or intake differences could compensate for these effects.

  18. Optically transmitted and inductively coupled electric reference to access in vivo concentrations for quantitative proton-decoupled ¹³C magnetic resonance spectroscopy.

    Science.gov (United States)

    Chen, Xing; Pavan, Matteo; Heinzer-Schweizer, Susanne; Boesiger, Peter; Henning, Anke

    2012-01-01

    This report describes our efforts on quantification of tissue metabolite concentrations in mM by nuclear Overhauser enhanced and proton decoupled (13) C magnetic resonance spectroscopy and the Electric Reference To access In vivo Concentrations (ERETIC) method. Previous work showed that a calibrated synthetic magnetic resonance spectroscopy-like signal transmitted through an optical fiber and inductively coupled into a transmit/receive coil represents a reliable reference standard for in vivo (1) H magnetic resonance spectroscopy quantification on a clinical platform. In this work, we introduce a related implementation that enables simultaneous proton decoupling and ERETIC-based metabolite quantification and hence extends the applicability of the ERETIC method to nuclear Overhauser enhanced and proton decoupled in vivo (13) C magnetic resonance spectroscopy. In addition, ERETIC signal stability under the influence of simultaneous proton decoupling is investigated. The proposed quantification method was cross-validated against internal and external reference standards on human skeletal muscle. The ERETIC signal intensity stability was 100.65 ± 4.18% over 3 months including measurements with and without proton decoupling. Glycogen and unsaturated fatty acid concentrations measured with the ERETIC method were in excellent agreement with internal creatine and external phantom reference methods, showing a difference of 1.85 ± 1.21% for glycogen and 1.84 ± 1.00% for unsaturated fatty acid between ERETIC and creatine-based quantification, whereas the deviations between external reference and creatine-based quantification are 6.95 ± 9.52% and 3.19 ± 2.60%, respectively. Copyright © 2011 Wiley Periodicals, Inc.

  19. Evaluation of the influence of fluoroquinolone chemical structure on stability: forced degradation and in silico studies

    Directory of Open Access Journals (Sweden)

    André Valle de Bairros

    2018-05-01

    Full Text Available ABSTRACT Fluoroquinolones are a known antibacterial class commonly used around the world. These compounds present relative stability and they may show some adverse effects according their distinct chemical structures. The chemical hydrolysis of five fluoroquinolones was studied using alkaline and photolytic degradation aiming to observe the differences in molecular reactivity. DFT/B3LYP-6.31G* was used to assist with understanding the chemical structure degradation. Gemifloxacin underwent degradation in alkaline medium. Gemifloxacin and danofloxacin showed more degradation perceptual indices in comparison with ciprofloxacin, enrofloxacin and norfloxacin in photolytic conditions. Some structural features were observed which may influence degradation, such as the presence of five member rings attached to the quinolone ring and the electrostatic positive charges, showed in maps of potential electrostatic charges. These measurements may be used in the design of effective and more stable fluoroquinolones as well as the investigation of degradation products from stress stability assays.

  20. Efflux pump induction by quaternary ammonium compounds and fluoroquinolone resistance in bacteria.

    Science.gov (United States)

    Buffet-Bataillon, Sylvie; Tattevin, Pierre; Maillard, Jean-Yves; Bonnaure-Mallet, Martine; Jolivet-Gougeon, Anne

    2016-01-01

    Biocides, primarily those containing quaternary ammonium compounds (QAC), are heavily used in hospital environments and various industries (e.g., food, water, cosmetic). To date, little attention has been paid to potential implications of QAC use in the emergence of antibiotic resistance, especially fluoroquinolone-resistant bacteria in patients and in the environment. QAC-induced overexpression of efflux pumps can lead to: cross resistance with fluoroquinolones mediated by multidrug efflux pumps; stress response facilitating mutation in the Quinolone Resistance Determining Region; and biofilm formation increasing the risk of transfer of mobile genetic elements carrying fluoroquinolone or QAC resistance determinants. By following the European Biocidal Product Regulation, manufacturers of QAC are required to ensure that their QAC-based biocidal products are safe and will not contribute to emerging bacterial resistance.

  1. In Vivo EPR Assessment of pH, pO2, Redox Status, and Concentrations of Phosphate and Glutathione in the Tumor Microenvironment.

    Science.gov (United States)

    Bobko, Andrey A; Eubank, Timothy D; Driesschaert, Benoit; Khramtsov, Valery V

    2018-03-16

    This protocol demonstrates the capability of low-field electron paramagnetic resonance (EPR)-based techniques in combination with functional paramagnetic probes to provide quantitative information on the chemical tumor microenvironment (TME), including pO2, pH, redox status, concentrations of interstitial inorganic phosphate (Pi), and intracellular glutathione (GSH). In particular, an application of a recently developed soluble multifunctional trityl probe provides unsurpassed opportunity for in vivo concurrent measurements of pH, pO2 and Pi in Extracellular space (HOPE probe). The measurements of three parameters using a single probe allow for their correlation analyses independent of probe distribution and time of the measurements.

  2. Ex vivo addition of fibrinogen concentrate improves the fibrin network structure in plasma samples taken during liver transplantation

    NARCIS (Netherlands)

    Groeneveld, D. J.; Adelmeijer, J.; Hugenholtz, G. C. G.; Ariens, R. A. S.; Porte, R. J.; Lisman, T.

    2015-01-01

    Background: Optimal hemostatic management during orthotopic liver transplantation (OLT) remains a challenge. The cause of bleeding during OLT is multifactorial, and may include hemostatic imbalance. Fibrinogen concentrates are increasingly being used to control perioperative bleeding during OLT.

  3. Fluoroquinolone-induced bilateral rupture of the Achilles tendon: clinical and sonographic findings

    Directory of Open Access Journals (Sweden)

    P. Busilacchi

    2011-09-01

    Full Text Available The fluoroquinolones are antibiotics widely used in the clinical practice. The concomitant use of corticosteroids and fluoroquinolones in elderly patients is recognised as a risk factor for developing clinically relevant tendon lesions. Fluoroquinolone-induced tendinopathy is underreported in the literature. Clinical case. A 67-year-old man, came to our observation complaining of 5 days history of bilateral heel pain. The patient had a medical history of sarcoidosis and was treated with a daily dose of 5 mg of prednisone. He was initially given oral levofloxacin (500 mg/die for 10 days, because of an acute respiratory infection. Two days before the end of the antibiotic therapy, he developed bilateral heel pain. He denied any history of trauma. Physical examination revealed swelling and marked tenderness with mild palpation of the Achilles tendons at the calcaneal insertion. The ultrasound evaluation of the Achilles tendons revealed the following main abnormalities: diffuse thickening, loss of the “fibrillar” echotexture, blurred margins, and bilateral partial tendon tears. Discussion. Bilateral Achilles tendon pain and rupture has been described as a rare adverse effect of fluoroquinolone treatment. Most of the fluoroquinolone-induced tendinopathies of the Achilles tendon are due to ciprofloxacin. To the best of our knowledge, this is the first description of bilateral Achilles tendon rupture due to levofloxacin. The risk/benefit ratio of the fluoroquinolones should be carefully considered and these drugs should be prescribed cautiously in elderly patients treated with corticosteroids. This case can be regarded as a representative example of the potential clinical efficacy of sonography in daily rheumatological practise.

  4. Evaluation of the appropriate use of commonly prescribed fluoroquinolones and the risk of dysglycemia

    Science.gov (United States)

    Kabbara, Wissam K; Ramadan, Wijdan H; Rahbany, Peggy; Al-Natour, Souhaila

    2015-01-01

    Background Fluoroquinolones are among the most widely prescribed antibiotics. However, concerns about increasing resistant microorganisms and the risk of dysglycemia associated with the use of these agents have emerged. Objective The primary objective of the study was to evaluate the appropriate use of commonly prescribed fluoroquinolones, including appropriate indication, dose, dose adjustment in renal impairment, and duration of treatment. The secondary objective was to investigate the dysglycemic effect of fluoroquinolone use (hypoglycemia and/or hyperglycemia) in diabetic and nondiabetic patients. Methods A prospective observational study at a teaching hospital in Lebanon was conducted over a 6-month period. A total of 118 patients receiving broad-spectrum fluoroquinolones (levofloxacin, ciprofloxacin, and moxifloxacin) were identified. Patients were mainly recruited from internal medicine floors and intensive care units. Results The final percentage for the appropriate indication, dose, and duration of fluoroquinolone therapy was 93.2%, 74.6%, and 57.6%, respectively. A total of 57.1% of the patients did not receive the appropriate dose adjustment according to their level of renal impairment. In addition, dysglycemia occurred in both diabetic and nondiabetic patients. Dysglycemia was more frequently encountered with ciprofloxacin (50.0%), followed by levofloxacin (42.4%) and moxifloxacin (7.6%). Hyperglycemia was more common than hypoglycemia in all groups. The highest incidence of hyperglycemia occurred with levofloxacin (70.0%), followed by ciprofloxacin (39.0%) and moxifloxacin (33.3%). In contrast, hypoglycemia did not occur in the ciprofloxacin group, but it was more common with moxifloxacin (11.1%) and levofloxacin (6.0%). Conclusion The major clinical interventions for the future will adjust the dose and duration of therapy with commonly prescribed fluoroquinolones. The incidence of hypoglycemia was less common than hyperglycemia. PMID:25960658

  5. Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a multidrug efflux transporter.

    OpenAIRE

    Neyfakh, A A; Borsch, C M; Kaatz, G W

    1993-01-01

    The gene of the Staphylococcus aureus fluoroquinolone efflux transporter protein NorA confers resistance to a number of structurally dissimilar drugs, not just to fluoroquinolones, when it is expressed in Bacillus subtilis. NorA provides B. subtilis with resistance to the same drugs and to a similar extent as the B. subtilis multidrug transporter protein Bmr does. NorA and Bmr share 44% sequence similarity. Both the NorA- and Bmr-conferred resistances can be completely reversed by reserpine.

  6. In vitro synergistic effect of fluoroquinolone analogues in combination with artemisinin against Plasmodium falciparum; their antiplasmodial action in rodent malaria model.

    Science.gov (United States)

    Agarwal, Drishti; Sharma, Manish; Dixit, Sandeep K; Dutta, Roshan K; Singh, Ashok K; Gupta, Rinkoo D; Awasthi, Satish K

    2015-02-05

    Emergence of drug-resistant parasite strains has surfaced as a major obstacle in attempts to ameliorate malaria. Current treatment regimen of malaria relies on the concept of artemisinin-based combination therapy (ACT). Fluoroquinolone analogues, compounds 10, 12 and 18 were investigated for their anti-malarial interaction in combination with artemisinin in vitro, against Plasmodium falciparum 3D7 strain, employing fixed-ratio combination isobologram method. In addition, the efficacy of these compounds was evaluated intraperitoneally in BALB/c mice infected with chloroquine-resistant Plasmodium berghei ANKA strain in the Peters' four-day suppressive test. Promising results were obtained in the form of synergistic or additive interactions. Compounds 10 and 12 were found to have highly synergistic interactions with artemisinin. Antiplasmodial effect was further verified by the convincing ED50 values of these compounds, which ranged between 2.31 and 3.09 (mg/kg BW). In vivo studies substantiated the potential of the fluoroquinolone derivatives to be developed as synergistic partners for anti-malarial drug combinations.

  7. Determination of fluoroquinolones in fish tissues, biological fluids, and environmental waters by liquid chromatography tandem mass spectrometry.

    Science.gov (United States)

    Ziarrusta, Haizea; Val, Nahia; Dominguez, Haizea; Mijangos, Leire; Prieto, Ailette; Usobiaga, Aresatz; Etxebarria, Nestor; Zuloaga, Olatz; Olivares, Maitane

    2017-11-01

    This work describes the optimization, validation, and application in real samples of accurate and precise analytical methods to determine ten fluoroquinolones (FQs) (norfloxacin, enoxacin, pefloxacin, ofloxacin, levofloxacin, ciprofloxacin, danofloxacin, lomefloxacin, enrofloxacin, and sparfloxacin) in different environmental matrices, such as water (estuarine, seawater, and wastewater treatment plant effluent), fish tissues (muscle and liver), and fish biofluids (plasma and bile). The analysis step performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was fully optimized to improve the separation and detection steps. The extraction of analytes from fish tissues was accomplished using focused ultrasound solid-liquid extraction using methanol/acetic acid (95:5 v/v) as extractant. The preconcentration and clean-up steps were optimized in terms of extraction efficiency and cleanliness and the best strategy for each matrix was selected: (i) Oasis HLB for seawater and muscle, (ii) liquid-liquid extraction combined with Oasis HLB for the lipid-rich liver, (iii) the combination of Evolute-WAX and Oasis HLB for estuarine water and wastewater treatment plant effluent, and (iv) molecular imprinted polymers for biofluids. The methods afforded satisfactory apparent recoveries (80-126%) and repeatability (RSD < 15%), except for sparfloxacin, which showed a lack of correction with the available isotopically labeled surrogates ([ 2 H 8 ]-ciprofloxacin and [ 2 H 5 ]-enrofloxacin). Ciprofloxacin, norfloxacin, and ofloxacin were detected in both water and fish liver samples from the Biscay Coast at concentrations up to 278 ng/L and 4 ng/g, respectively. To the best of our knowledge, this work is one of the few analyzing up to ten FQs and in so many fish tissues and biofluids. Graphical abstract Determination of fluoroquinolones in different environmental matrices, such as water (estuarine, seawater, and wastewater treatment plant effluent), fish tissues (muscle

  8. A novel sensor based on electropolymerization of β-cyclodextrin and L-arginine on carbon paste electrode for determination of fluoroquinolones

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Fenfen [School of Materials Science and Engineering, Shanghai University, Shanghai 200444 (China); Gu, Shuqing [Department of Chemistry, Shanghai University, Shanghai 200444 (China); School of Materials Science and Engineering, Shanghai University, Shanghai 200444 (China); Ding, Yaping, E-mail: wdingyp@sina.com [Department of Chemistry, Shanghai University, Shanghai 200444 (China); School of Materials Science and Engineering, Shanghai University, Shanghai 200444 (China); Zhang, Zhen [School of Materials Science and Engineering, Shanghai University, Shanghai 200444 (China); School of Chemistry and Chemical Engineering, Linyi University, 18 TongDa Road, Linyi 276005 (China); Li, Li [Department of Chemistry, Shanghai University, Shanghai 200444 (China)

    2013-04-03

    Graphical abstract: The inner cavities of β-CD could restrain fluoroquinolones to form stable host–guest inclusion complexes, and the guanidyl group of L-arg could enable L-arg to form electrostatic interactions with negatively charged groups -COO{sup −} of fluoroquinolones. Highlights: ► Electropolymerization of β-cyclodextrin and L-arginine on carbon paste electrode. ► The electrooxidation and reaction of FQs on the modified CPE were surmised. ► The sensor is used to detect ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. ► Determine FQs drugs in pharmaceutical formulations and human serum samples. ► It showed high stability, repeatability, reproducibility, good sensitivity. -- Abstract: An electrochemical sensor for fluoroquinolones (FQs) based on polymerization of β-cyclodextrin (β-CD) and L-arginine (L-arg) modified carbon paste electrode (CPE) (P-β-CD-L-arg/CPE) was built for the first time. Synergistic effect of L-arg and β-CD was used to construct this sensor for quantification of these important antibiotics. Scanning electron microscope (SEM) image shows that polymer of β-CD and L-arg has been successfully modified on electrode. Electrochemical impedance spectroscopy (EIS) and cyclic voltammograms (CV) further indicate that polymer of β-CD and L-arg efficiently decreased the charge transfer resistance value of electrode and improved the electron transfer kinetic between analyte and electrode. Under the optimized conditions, this modified electrode was utilized to determine the concentrations of ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. The differential pulse voltammogram (DPV) exhibits the oxidation peak currents were linearly proportional to their concentration in the range of 0.05–100 μM for ciprofloxacin, 0.1–100 μM for ofloxacin, 0.1–40 μM for norfloxacin and 0.06–100 μM for gatifloxacin, respectively. This method was also successfully used to detect the concentrations of each drug in

  9. A novel sensor based on electropolymerization of β-cyclodextrin and L-arginine on carbon paste electrode for determination of fluoroquinolones

    International Nuclear Information System (INIS)

    Zhang, Fenfen; Gu, Shuqing; Ding, Yaping; Zhang, Zhen; Li, Li

    2013-01-01

    Graphical abstract: The inner cavities of β-CD could restrain fluoroquinolones to form stable host–guest inclusion complexes, and the guanidyl group of L-arg could enable L-arg to form electrostatic interactions with negatively charged groups -COO − of fluoroquinolones. Highlights: ► Electropolymerization of β-cyclodextrin and L-arginine on carbon paste electrode. ► The electrooxidation and reaction of FQs on the modified CPE were surmised. ► The sensor is used to detect ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. ► Determine FQs drugs in pharmaceutical formulations and human serum samples. ► It showed high stability, repeatability, reproducibility, good sensitivity. -- Abstract: An electrochemical sensor for fluoroquinolones (FQs) based on polymerization of β-cyclodextrin (β-CD) and L-arginine (L-arg) modified carbon paste electrode (CPE) (P-β-CD-L-arg/CPE) was built for the first time. Synergistic effect of L-arg and β-CD was used to construct this sensor for quantification of these important antibiotics. Scanning electron microscope (SEM) image shows that polymer of β-CD and L-arg has been successfully modified on electrode. Electrochemical impedance spectroscopy (EIS) and cyclic voltammograms (CV) further indicate that polymer of β-CD and L-arg efficiently decreased the charge transfer resistance value of electrode and improved the electron transfer kinetic between analyte and electrode. Under the optimized conditions, this modified electrode was utilized to determine the concentrations of ciprofloxacin, ofloxacin, norfloxacin and gatifloxacin. The differential pulse voltammogram (DPV) exhibits the oxidation peak currents were linearly proportional to their concentration in the range of 0.05–100 μM for ciprofloxacin, 0.1–100 μM for ofloxacin, 0.1–40 μM for norfloxacin and 0.06–100 μM for gatifloxacin, respectively. This method was also successfully used to detect the concentrations of each drug in pharmaceutical

  10. Non-invasive measurement and imaging of tissue iron oxide nanoparticle concentrations in vivo using proton relaxometry

    International Nuclear Information System (INIS)

    St Pierre, T G; Clark, P R; Chua-anusorn, W; Fleming, A; Pardoe, H; Jeffrey, G P; Olynyk, J K; Pootrakul, P; Jones, S; Moroz, P

    2005-01-01

    Magnetic nanoparticles and microparticles can be found in biological tissues for a variety of reasons including pathological deposition of biogenic particles, administration of synthetic particles for scientific or clinical reasons, and the inclusion of biogenic magnetic particles for the sensing of the geomagnetic field. In applied magnetic fields, the magnetisation of tissue protons can be manipulated with radiofrequency radiation such that the macroscopic magnetisation of the protons precesses freely in the plane perpendicular to the applied static field. The presence of magnetic particles within tissue enhances the rate of dephasing of proton precession with higher concentrations of particles resulting in higher dephasing rates. Magnetic resonance imaging instruments can be used to measure and image the rate of decay of spin echo recoverable proton transverse magnetisation (R 2 ) within tissues enabling the measurement and imaging of magnetic particle concentrations with the aid of suitable calibration curves. Applications include the non-invasive measurement of liver iron concentrations in iron-overload disorders and measurement and imaging of magnetic particle concentrations used in magnetic hyperthermia therapy. Future applications may include the tracking of magnetically labelled drugs or biomolecules and the measurement of fibrotic liver damage

  11. Compact DD generator based in vivo neutron activation analysis (IVNAA) system to determine sodium concentrations in human bone.

    Science.gov (United States)

    Coyne, Mychaela Dawn; Neumann, Colby R; Zhang, Xinxin; Byrne, Patrick; Liu, Yingzi; Weaver, Connie M; Nie, Linda Huiling

    2018-04-16

    This study presents the development of a non-invasive method for monitoring Na in human bone. Many diseases, such as hypertension and osteoporosis, are closely associated with sodium (Na) retention in the human body. Na retention is generally evaluated by calculating the difference between dietary intake and excretion. There is currently no method to directly quantify Na retained in the body. Bone is a storage for many elements, including Na, which renders bone Na an ideal biomarker to study Na metabolism and retention. Approach: A customized compact deuterium-deuterium (DD) neutron generator was used to produce neutrons for in vivo neutron activation analysis (IVNAA), with a moderator/ reflector/ shielding assembly optimized for human hand irradiation in order to maximize the thermal neutron flux inside the irradiation cave and to limit radiation exposure to the hand and the whole body. Main Results: The experimental results show that the system is able to detect sodium levels in the bone as low as 12 g Na/g dry bone with an effective dose to the body of about 27 μSv. The simulation results agree with the numbers estimated from the experiment. Significance: This is expected to be a feasible method for measuring the change of Na in bone. The low detection limit indicates this will be a useful system to study the association between Na retention and related diseases. © 2018 Institute of Physics and Engineering in Medicine.

  12. Fabrication of Implantable, Enzyme-Immobilized Glutamate Sensors for the Monitoring of Glutamate Concentration Changes in Vitro and in Vivo

    Directory of Open Access Journals (Sweden)

    Tina T.-C. Tseng

    2014-06-01

    Full Text Available Glutamate sensors based on the immobilization of glutamate oxidase (GlutOx were prepared by adsorption on electrodeposited chitosan (Method 1 and by crosslinking with glutaraldehyde (Method 2 on micromachined platinum microelectrodes. It was observed that glutamate sensors prepared by Method 1 have faster response time (<2 s and lower detection limit (2.5 ± 1.1 μM compared to that prepared by Method 2 (response time: <5 sec and detection limit: 6.5 ± 1.7 μM; glutamate sensors prepared by Method 2 have a larger linear detection range (20–352 μM and higher sensitivity (86.8 ± 8.8 nA·μM−1·cm−2, N = 12 compared to those prepared by Method 1 (linear detection range: 20–217 μM and sensitivity: 34.9 ± 4.8 nA·μM−1·cm−2, N = 8. The applicability of the glutamate sensors in vivo was also demonstrated. The glutamate sensors were implanted into the rat brain to monitor the stress-induced extracellular glutamate release in the hypothalamus of the awake, freely moving rat.

  13. Variation in the bone calcium concentration as a function of age and sex, studied by local neutron activation in vivo

    International Nuclear Information System (INIS)

    Mazieres, B.; Comar, D.

    An original method of local activation on the hand, using isotopic neutron sources, was used to determine bone Ca and P simultaneously. The calcium concentration variation with age and sex was studied on 120 normal subjects men and women aged between 20 and 80, divided into 10 year age groups. These standards were chosen amongst subjects free from complaints liable to affect bone mineralisation and with more or less normal blood calcium and phosphorus contents. The results are as follows: between 20 and 50 the relative standard derivation observed within a 10 year age group averages 8% in men and 9% in women, after 50 this physiological scattering is much greater in both sexes, after 60 the bone calcium concentration decreases quickly in women at an average rate of 1.15% a year [fr

  14. Dermal inorganic gadolinium concentrations: evidence for in vivo transmetallation and long-term persistence in nephrogenic systemic fibrosis

    DEFF Research Database (Denmark)

    Abraham, J L; Thakral, C; Skov, L

    2008-01-01

    BACKGROUND: Gadolinium (Gd)-based magnetic resonance contrast agents (GBMCA), including gadodiamide, have been identified as the probable causative agents of the serious disease, nephrogenic systemic fibrosis (NSF). OBJECTIVES: To investigate retained Gd-containing deposits in skin biopsies from...... patients with NSF and to determine their relative concentrations over time from administration of GBMCA. METHODS: An investigator-blinded retrospective study, analysing 43 skin biopsies from 20 patients with gadodiamide-related NSF and one NSF-negative gadodiamide-exposed dialysis patient, ranging from 16...... days to 1991 days after Gd contrast dose. Utilizing automated quantitative scanning electron microscopy/energy-dispersive X-ray spectroscopy we determined the concentration of Gd and associated elements present as insoluble deposits in situ in the tissues. RESULTS: We detected Gd in skin lesions of all...

  15. Biotransformation of fluoroquinolone antibiotics by ligninolytic fungi - Metabolites, enzymes and residual antibacterial activity

    Czech Academy of Sciences Publication Activity Database

    Čvančarová, Monika; Moeder, M.; Filipová, Alena; Cajthaml, Tomáš

    2015-01-01

    Roč. 136, OCT 2015 (2015), s. 311-320 ISSN 0045-6535 R&D Projects: GA TA ČR TE01020218; GA ČR GA13-28283S Institutional support: RVO:61388971 Keywords : Fluoroquinolone antibiotics * White rot fungi * Residual antibacterial activity Subject RIV: EE - Microbiology, Virology Impact factor: 3.698, year: 2015

  16. Comparison of a fluoroquinolone surface plasmon resonance biosensor screening assay with established methods

    NARCIS (Netherlands)

    Weigel, S.; Pikkemaat, M.G.; Elferink, J.W.A.; Mulder, P.P.J.; Huet, A.C.; Delahaut, P.; Schittko, S.; Flerus, R.; Nielen, M.W.F.

    2009-01-01

    The performance of a previously developed immunochemical biosensor screening method for fluoroquinolone (FQ) antibiotics in poultry muscle, fish and egg was compared with established methods. Blank sample material of the target matrices was individually spiked with the FQs at half maximum residue

  17. Intravenous to oral conversion of fluoroquinolones: knowledge versus clinical practice patterns.

    Science.gov (United States)

    Conort, Ornella; Gabardi, Steven; Didier, Marie-Pauline; Hazebroucq, Georges; Cariou, Alain

    2002-04-01

    To assess the knowledge of prescribers regarding intravenous to oral conversions of fluoroquinolones, the frequency and time until conversion, and to compare prescriber knowledge with the data collected concerning the reasons stated for continuation of intravenous fluoroquinolones. Prospective chart review and questionnaire. Large teaching hospital in Paris, France. Fifty-one males and females. Data were collected on in-patients receiving intravenous fluoroquinolone for at least three days and hospitalized in one of six in-patient units. Patients receiving intravenous fluoroquinolone for less than three days were excluded. A questionnaire to assess the awareness of a potential conversion was distributed to those practitioners who had patients reviewed during the data-collection phase. The questionnaire revealed the ten most common reasons for continuing intravenous administration for more than three days. However, the physicians agreed that most patients should be converted as soon as possible. Practice patterns differed, with only 17 of 51 patients actually converted to oral therapy. In theory, the clinicians were aware of when to perform the conversion. However, in practice, the frequency of conversion was lower than optimum. Changes in clinical practice are needed to decrease the costs of intravenous therapy, without jeopardizing quality of care.

  18. Fluoroquinolones impair tendon healing in a rat rotator cuff repair model: a preliminary study.

    Science.gov (United States)

    Fox, Alice J S; Schär, Michael O; Wanivenhaus, Florian; Chen, Tony; Attia, Erik; Binder, Nikolaus B; Otero, Miguel; Gilbert, Susannah L; Nguyen, Joseph T; Chaudhury, Salma; Warren, Russell F; Rodeo, Scott A

    2014-12-01

    Recent studies suggest that fluoroquinolone antibiotics predispose tendons to tendinopathy and/or rupture. However, no investigations on the reparative capacity of tendons exposed to fluoroquinolones have been conducted. Fluoroquinolone-treated animals will have inferior biochemical, histological, and biomechanical properties at the healing tendon-bone enthesis compared with controls. Controlled laboratory study. Ninety-two rats underwent rotator cuff repair and were randomly assigned to 1 of 4 groups: (1) preoperative (Preop), whereby animals received fleroxacin for 1 week preoperatively; (2) pre- and postoperative (Pre/Postop), whereby animals received fleroxacin for 1 week preoperatively and for 2 weeks postoperatively; (3) postoperative (Postop), whereby animals received fleroxacin for 2 weeks postoperatively; and (4) control, whereby animals received vehicle for 1 week preoperatively and for 2 weeks postoperatively. Rats were euthanized at 2 weeks postoperatively for biochemical, histological, and biomechanical analysis. All data were expressed as mean ± standard error of the mean (SEM). Statistical comparisons were performed using either 1-way or 2-way ANOVA, with P repair response that has potential clinical implications for patients who are exposed to fluoroquinolones before tendon repair surgery. © 2014 The Author(s).

  19. Resistance to fluoroquinolones and second-line injectable drugs: impact on multidrug-resistant TB outcomes

    NARCIS (Netherlands)

    Falzon, Dennis; Gandhi, Neel; Migliori, Giovanni B.; Sotgiu, Giovanni; Cox, Helen S.; Holtz, Timothy H.; Hollm-Delgado, Maria-Graciela; Keshavjee, Salmaan; Deriemer, Kathryn; Centis, Rosella; D'Ambrosio, Lia; Lange, Christoph G.; Bauer, Melissa; Menzies, Dick; Ahuja, S. D.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Becerra, M. C.; Benedetti, A.; Burgos, M.; Centis, R.; Chan, E. D.; Chiang, C. Y.; Cobelens, F.; Cox, H.; D'Ambrosio, L.; de Lange, W. C. M.; DeRiemer, K.; Enarson, D.; Falzon, D.; Flanagan, K. L.; Flood, J.; Gandhi, N.; Garcia-Garcia, M. L.; Granich, R. M.; Hollm-Delgado, M. G.; Holtz, T. H.; Hopewell, P.; Iseman, M. D.; Jarlsberg, L. G.; Keshavjee, S.; Kim, H. R.; Koh, W. J.; Lancaster, J. L.; Lange, C.; Leimane, V.; Leung, C. C.; Li, J.

    2013-01-01

    A meta-analysis for response to treatment was undertaken using individual data of multidrug-resistant tuberculosis (MDR-TB) (resistance to isoniazid and rifampicin) patients from 26 centres. The analysis assessed the impact of additional resistance to fluoroquinolones and/or second-line injectable

  20. Biodegradable drug-eluting nanofiber-enveloped implants for sustained release of high bactericidal concentrations of vancomycin and ceftazidime: in vitro and in vivo studies

    Directory of Open Access Journals (Sweden)

    Hsu YH

    2014-09-01

    Full Text Available Yung-Heng Hsu,1,2 Dave Wei-Chih Chen,1 Chun-Der Tai,3 Ying-Chao Chou,1,2 Shih-Jung Liu,2 Steve Wen-Neng Ueng,1 Err-Cheng Chan4 1Department of Orthopedic Surgery, Chang Gung Memorial Hospital, Guishan Township, 2Department of Mechanical Engineering, Chang Gung University, Guishan Township, 3Graduate Institute of Medical Mechatronics, Chang Gung University, Guishan Township, 4School of Medical Technology, Chang Gung University, Guishan Township, Taiwan Abstract: We developed biodegradable drug-eluting nanofiber-enveloped implants that provided sustained release of vancomycin and ceftazidime. To prepare the biodegradable nanofibrous membranes, poly(D,L-lactide-co-glycolide and the antibiotics were first dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol. They were electrospun into biodegradable drug-eluting membranes, which were then enveloped on the surface of stainless plates. An elution method and a high-performance liquid chromatography assay were employed to characterize the in vivo and in vitro release rates of the antibiotics from the nanofiber-enveloped plates. The results showed that the biodegradable nanofiber-enveloped plates released high concentrations of vancomycin and ceftazidime (well above the minimum inhibitory concentration for more than 3 and 8 weeks in vitro and in vivo, respectively. A bacterial inhibition test was carried out to determine the relative activity of the released antibiotics. The bioactivity ranged from 25% to 100%. In addition, the serum creatinine level remained within the normal range, suggesting that the high vancomycin concentration did not affect renal function. By adopting the electrospinning technique, we will be able to manufacture biodegradable drug-eluting implants for the long-term drug delivery of different antibiotics. Keywords: biodegradable nanofiber-enveloped plates, electrospinning, antibiotics, release characteristics

  1. Evaluation of the appropriate use of commonly prescribed fluoroquinolones and the risk of dysglycemia

    Directory of Open Access Journals (Sweden)

    Kabbara WK

    2015-04-01

    Full Text Available Wissam K Kabbara,1 Wijdan H Ramadan,1 Peggy Rahbany,2 Souhaila Al-Natour3 1Department of Pharmacy Practice, School of Pharmacy, Lebanese American University, Byblos, Lebanon; 2Children’s National Medical Center, Washington, DC, USA; 3Medex Pharmaceutical Company, Beirut, Lebanon Background: Fluoroquinolones are among the most widely prescribed antibiotics. However, concerns about increasing resistant microorganisms and the risk of dysglycemia associated with the use of these agents have emerged.Objective: The primary objective of the study was to evaluate the appropriate use of commonly prescribed fluoroquinolones, including appropriate indication, dose, dose adjustment in renal impairment, and duration of treatment. The secondary objective was to investigate the dysglycemic effect of fluoroquinolone use (hypoglycemia and/or hyperglycemia in diabetic and nondiabetic patients.Methods: A prospective observational study at a teaching hospital in Lebanon was conducted over a 6-month period. A total of 118 patients receiving broad-spectrum fluoroquinolones (levofloxacin, ciprofloxacin, and moxifloxacin were identified. Patients were mainly recruited from internal medicine floors and intensive care units.Results: The final percentage for the appropriate indication, dose, and duration of fluoroquinolone therapy was 93.2%, 74.6%, and 57.6%, respectively. A total of 57.1% of the patients did not receive the appropriate dose adjustment according to their level of renal impairment. In addition, dysglycemia occurred in both diabetic and nondiabetic patients. Dysglycemia was more frequently encountered with ciprofloxacin (50.0%, followed by levofloxacin (42.4% and moxifloxacin (7.6%. Hyperglycemia was more common than hypoglycemia in all groups. The highest incidence of hyperglycemia occurred with levofloxacin (70.0%, followed by ciprofloxacin (39.0% and moxifloxacin (33.3%. In contrast, hypoglycemia did not occur in the ciprofloxacin group, but it was

  2. Effect of DSPE-PEG on compound action potential, injury potential and ion concentration following compression in ex vivo spinal cord.

    Science.gov (United States)

    Wang, Aihua; Huo, Xiaolin; Zhang, Guanghao; Wang, Xiaochen; Zhang, Cheng; Wu, Changzhe; Rong, Wei; Xu, Jing; Song, Tao

    2016-05-04

    It has been shown that polyethylene glycol (PEG) can reseal membrane disruption on the spinal cord, but only high concentrations of PEG have been shown to have this effect. Therefore, the effect of PEG is somewhat limited, and it is necessary to investigate a new approach to repair spinal cord injury. This study assesses the ability of 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(poly (ethylene glycol)) 2000] (DSPE-PEG) to recover physiological function and attenuate the injury-induced influx of extracellular ions in ex vivo spinal cord injury. Isolated spinal cords were subjected to compression injury and treated with PEG or DSPE-PEG immediately after injury. The compound action potential (CAP) was recorded before and after injury to assess the functional recovery. Furthermore, injury potential, the difference in gap potentials before and after compression, and the concentration of intracellular ions were used to evaluate the effect of DSPE-PEG on reducing ion influx. Data showed that the injury potential and ion concentration of the untreated, PEG and DSPE-PEG group, without significant difference among them, are remarkably higher than those of the intact group. Moreover, the CAP recovery of the DSPE-PEG and PEG treated spinal cords was significantly greater than that of the untreated spinal cords. The level of CAP recovery in the DSPE-PEG and PEG treated groups was the same, but the concentration of DSPE-PEG used was much lower than the concentration of PEG. These results suggest that instant application of DSPE-PEG could effectively repair functional disturbance in SCI at a much lower concentration than PEG. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Evidence of In Vivo Absorption of Lactate and Modulation of Short Chain Fatty Acid Absorption from the Reticulorumen of Non-Lactating Cattle Fed High Concentrate Diets.

    Directory of Open Access Journals (Sweden)

    Muhammad Qumar

    Full Text Available Short-chain fatty acids (SCFAs and lactate are endproducts of rumen fermentation and important energy sources for the host ruminant. Because their rapid accumulation results in ruminal acidosis, enhancement of the absorption of SCFA and lactate across reticuloruminal wall is instrumental in increasing energy supply and preventing ruminal acidosis in cattle. This study investigated whether the reticuloruminal absorption of SCFAs and lactate was altered by different strategies of high concentrate feeding. Eight rumen-cannulated, non-lactating Holstein cows were fed a forage-only diet (baseline and then gradually adapted over 6 d to a 60% concentrate level. Thereafter, this concentrate-rich diet was fed for 4 wk either continuously (Con; n = 8 or interruptedly (Int; n = 8. Absorption of SCFAs and lactate was determined in vivo from the experimental buffer introduced into the washed reticulorumen. The buffer contained acetate, propionate, butyrate and lactate at a concentration of 60, 30, 10 and 5 mmol/L, respectively and Cr-EDTA as a marker for correcting ruminal water fluxes. The reticuloruminal absorption after 35 and 65 min of buffer incubation was measured at the baseline, after 1 wk of 60% concentrate feeding in the interrupted model (Int-1 and after 4 wk of concentrate feeding in both feeding models (Int-4 and Con-4. Data showed that the absorption rates of individual and total SCFAs during the first 35 min of incubation of Con-4 were highest (~1.7 times compared to baseline, while Int-1 and Int-4 were similar to respective baseline. Lactate was not absorbed during forage-only baseline and 1-wk concentrate feeding, but after 4-wk feeding of concentrates in both models. In conclusion, SCFAs absorption across the reticulorumen of non-lactating cattle was enhanced by the 4-wk continuous concentrate feeding, which seems to be more advantageous in terms of rumen acidosis prevention compared to the interrupted feeding model. The study provides

  4. Fumonisin concentrations and in vivo toxicity of nixtamalized Fusarium verticillioides culture material: evidence for fumonisin-matrix interactions.

    Science.gov (United States)

    Burns, T D; Snook, M E; Riley, R T; Voss, K A

    2008-08-01

    The toxic potential of nixtamalized foods can be underestimated if, during cooking, reversible fumonisin-food matrix interactions reduce the amount of mycotoxin that is detected but not the amount that is bioavailable. Fusarium verticillioides culture material (CM) was nixtamalized as is (NCM) or after mixing with ground corn (NCMC). Additional portions were sham nixtamalized without (SCM) or with corn (SCMC). Nixtamalization and sham nixtamalization reduced FB(1); CM, NCM, and SCM diets contained 9.08, 2.08, and 1.19 ppm, respectively. FB(1) was further reduced in the NCMC (0.49 ppm) but not the SCMC (1.01 ppm) diets compared to their NCM and SCM counterparts. Equivalent weights of the cooked products, uncooked CM, corn (UC) or nixtamalized UC (NUC) were fed to rats for up to three weeks. Kidney lesions in the NCM-fed group were less severe than in the CM-fed, positive control group and no lesions were found in the NCMC and other groups. Group kidney sphinganine (biomarker of fumonisin exposure) concentrations decreased in the order: CM (absolute concentration (nmol/g)=600-800)>NCM (400-600)>SCM and SCMC (30-90)>NCMC, UC and NUC (<8). Together, these results suggest that mycotoxin-corn matrix interactions during nixtamalization reduce the bioavailability and toxicity of FB(1).

  5. Rate of bacterial eradication by ophthalmic solutions of fourth-generation fluoroquinolones.

    Science.gov (United States)

    Callegan, Michelle C; Novosad, Billy D; Ramadan, Raniyah T; Wiskur, Brandt; Moyer, Andrea L

    2009-04-01

    Antibacterial activity of ophthalmic fourth-generation fluoroquinolones has traditionally been evaluated by comparing only their active ingredients, gatifloxacin and moxifloxacin. However, ophthalmic formulations of fourth-generation fluoroquinolones differ in terms of the inclusion of preservatives. While gatifloxacin ophthalmic solution 0.3% (Zymar; Allergan, Inc., Irvine, CA, USA) contains 0.005% benzalkonium chloride (BAK), moxifloxacin ophthalmic solution 0.5% (Vigamox; Alcon Laboratories, Inc., Fort Worth, TX, USA) is preservative-free. Recent studies have demonstrated that the presence of BAK dramatically affects the antibacterial activity of the ophthalmic formulation of gatifloxacin. This study was designed to compare the kill rates of ophthalmic solutions of fourth-generation fluoroquinolones against isolates of common ocular bacterial pathogens. Approximately 5.6 log(10) colony-forming units (CFU)/mL of Haemophilus influenzae (n=1), Streptococcus pneumoniae (n=1), Staphylococcus aureus (n=2), methicillin-resistant Staphylococcus aureus (MRSA) (n=4), methicillinresistant Staphylococcus epidermidis (MRSE) (n=4), and fluoroquinolone-resistant S. epidermidis (n=1) were incubated with ophthalmic solutions of either gatifloxacin or moxifloxacin. Viable bacteria were quantified at specific time points up to 60 minutes. Gatifloxacin 0.3% completely eradicated H. influenzae and Strep. pneumoniae in 5 minutes, one of two S. aureus isolates in 15 minutes, and the other S. aureus isolate in 60 minutes. Gatifloxacin 0.3% completely killed all MRSA, MRSE, and fluoroquinolone-resistant S. epidermidis isolates in 15 minutes. Moxifloxacin 0.5% completely eradicated Strep. pneumoniae and one of four MRSA isolates in 60 minutes. All other isolates incubated with moxifloxacin 0.5% retained viable bacteria ranging from 1.8 to 4.4 log(10) CFU/mL. The ophthalmic solution of gatifloxacin 0.3% eradicated bacteria that frequently cause postoperative ocular infections

  6. Preclinical in vitro and in vivo evaluation of [11C]SNAP-7941 – the first PET tracer for the melanin concentrating hormone receptor 1

    International Nuclear Information System (INIS)

    Philippe, Cécile; Nics, Lukas; Zeilinger, Markus; Kuntner, Claudia; Wanek, Thomas; Mairinger, Severin; Shanab, Karem; Spreitzer, Helmut; Viernstein, Helmut; Wadsak, Wolfgang; Mitterhauser, Markus

    2013-01-01

    Introduction: Due to its involvement in a variety of pathologies (obesity, diabetes, gut inflammation and depression), the melanin concentrating hormone receptor 1 (MCHR1) is a new target for the treatment of these lifestyle diseases. We previously presented the radiosynthesis of [ 11 C]SNAP-7941, the first potential PET tracer for the MCHR1. Methods: We herein present its in vitro and in vivo evaluation, including binding affinity, plasma stability, stability against liver mircrosomes and carboxylesterase, lipohilicity, biodistribution, in vivo metabolism and small-animal PET. Results: [ 11 C]SNAP-7941 evinced high stability against liver microsomes, carboxylesterase and in human plasma. The first small-animal PET experiments revealed a 5 fold increased brain uptake after Pgp/BCRP inhibition. Therefore, it can be assumed that [ 11 C]SNAP-7941 is a Pgp/BCRP substrate. No metabolites were found in brain. Conclusion: On the basis of these experiments with healthy rats, the suitability of [ 11 C]SNAP-7941 for the visualisation of central and peripheral MCHR1 remains speculative

  7. Attempt to demonstrate an in vivo effect of mianserin hydrochloride on erythrocyte Na+-K+-ATPase activity and cyclic AMP concentration

    Science.gov (United States)

    Naylor, G. S.; Buckley, D. E.; Boardman, L. J.; Smith, A. H. W.; Moody, J. P.

    1978-01-01

    1 There is evidence that erythrocyte Na+-K+-ATPase activity and erythrocyte cyclic AMP change on recovery from a depressive illness. Mianserin is a recently introduced antidepressant but its mode of action is unknown. The present study was therefore designed to investigate in vivo the effect of mianserin on erythrocyte Na+-K+-ATPase and cyclic AMP. 2 Biochemical estimations were made on blood from depressed patients before beginning either mianserin or matched placebo treatment, after 1 week, and again after 2 weeks' treatment. 3 Neither the erythrocyte Na+-K+-ATPase, nor the erythrocyte cyclic AMP concentration, changed significantly in either the mianserin- or the placebo-treated group. 4 The study sheds no light on the possible mechanism of action of mianserin. PMID:203308

  8. Fluoroquinolone resistance mechanisms in urinary tract pathogenic Escherichia coli isolated during rapidly increasing fluoroquinolone consumption in a low-use country

    DEFF Research Database (Denmark)

    Christiansen, Nina; Nielsen, Lene; Jakobsen, Lotte

    2011-01-01

    Resistance to ciprofloxacin in Escherichia coli from urinary tract infections (UTI) in Denmark is increasing parallel to increased use of fluoroquinolones both in Denmark and in other European countries. The objective was to investigate the occurrence of ciprofloxacin resistance mechanisms......, phenotypic coresistance, and if ciprofloxacin resistance was caused by clonal spread or to individual mutational events in a collection of consecutively obtained E. coli submitted to a clinical microbiology department at a Danish hospital. One hundred four UTI-related E. coli resistant toward nalidixic acid...

  9. Risk factors associated with fluoroquinolone-resistant enterococcal urinary tract infections in a tertiary care university hospital in north India

    Directory of Open Access Journals (Sweden)

    Tuhina Banerjee

    2016-01-01

    Interpretation & conclusions: Our results showed that fluoroquinolone resistance in enterococcal UTI was largely associated with indoor usage of antibiotics and use of indwelling devices. Knowledge of risk factors is important to curb this emergence of resistance.

  10. The mixture of "ecstasy" and its metabolites impairs mitochondrial fusion/fission equilibrium and trafficking in hippocampal neurons, at in vivo relevant concentrations.

    Science.gov (United States)

    Barbosa, Daniel José; Serrat, Romàn; Mirra, Serena; Quevedo, Martí; de Barreda, Elena Goméz; Àvila, Jesús; Ferreira, Luísa Maria; Branco, Paula Sério; Fernandes, Eduarda; Lourdes Bastos, Maria de; Capela, João Paulo; Soriano, Eduardo; Carvalho, Félix

    2014-06-01

    3,4-Methylenedioxymethamphetamine (MDMA; "ecstasy") is a potentially neurotoxic recreational drug of abuse. Though the mechanisms involved are still not completely understood, formation of reactive metabolites and mitochondrial dysfunction contribute to MDMA-related neurotoxicity. Neuronal mitochondrial trafficking, and their targeting to synapses, is essential for proper neuronal function and survival, rendering neurons particularly vulnerable to mitochondrial dysfunction. Indeed, MDMA-associated disruption of Ca(2+) homeostasis and ATP depletion have been described in neurons, thus suggesting possible MDMA interference on mitochondrial dynamics. In this study, we performed real-time functional experiments of mitochondrial trafficking to explore the role of in situ mitochondrial dysfunction in MDMA's neurotoxic actions. We show that the mixture of MDMA and six of its major in vivo metabolites, each compound at 10μM, impaired mitochondrial trafficking and increased the fragmentation of axonal mitochondria in cultured hippocampal neurons. Furthermore, the overexpression of mitofusin 2 (Mfn2) or dynamin-related protein 1 (Drp1) K38A constructs almost completely rescued the trafficking deficits caused by this mixture. Finally, in hippocampal neurons overexpressing a Mfn2 mutant, Mfn2 R94Q, with impaired fusion and transport properties, it was confirmed that a dysregulation of mitochondrial fission/fusion events greatly contributed to the reported trafficking phenotype. In conclusion, our study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at concentrations relevant to the in vivo scenario, impaired mitochondrial trafficking and increased mitochondrial fragmentation in hippocampal neurons, thus providing a new insight in the context of "ecstasy"-induced neuronal injury.

  11. In vivo degradation behavior and biological activity of some new Mg-Ca alloys with concentration's gradient of Si for bone grafts

    Science.gov (United States)

    Trincă, Lucia Carmen; Fântânariu, Mircea; Solcan, Carmen; Trofin, Alina Elena; Burtan, Liviu; Acatrinei, Dumitru Mihai; Stanciu, Sergiu; Istrate, Bogdan; Munteanu, Corneliu

    2015-10-01

    Magnesium based alloys, especially Mg-Ca alloys, are biocompatible substrates with mechanical properties similar to those of bones. The biodegradable alloys of Mg-Ca provide sufficient mechanical strength in load carrying applications as opposed to biopolymers and also they avoid stress shielding and secondary surgery inherent with permanent metallic implant materials. The main issue facing a biodegradable Mg-Ca alloy is the fast degradation in the aggressive physiological environment of the body. The alloy's corrosion is proportional with the dissolution of the Mg in the body: the reaction with the water generates magnesium hydroxide and hydrogen. The accelerated corrosion will lead to early loss of the alloy's mechanical integrity. The degradation rate of an alloy can be improved mainly through tailoring the composition and by carrying out surface treatments. This research focuses on the ability to adjust degradation rate of Mg-Ca alloys by an original method and studies the biological activity of the resulted specimens. A new Mg-Ca alloy, with a Si gradient concentration from the surface to the interior of the material, was obtained. The surface morphology was investigated using scanning electron microscopy (VegaTescan LMH II, SE detector, 30 kV), X-ray diffraction (X'Pert equipment) and energy dispersive X-ray (Bruker EDS equipment). In vivo degradation behavior, biological compatibility and activity of Mg-Ca alloys with/without Si gradient concentration were studied with an implant model (subcutaneous and bony) in rats. The organism response to implants was characterized by using radiological (plain X-rays and computed tomography), biochemical and histological methods of investigation. The results sustained that Si gradient concentration can be used to control the rate of degradation of the Mg-Ca alloys for enhancing their biologic activity in order to facilitate bone tissue repair.

  12. Phenotypic and genetic characteristics of fluoroquinolone- and methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Moreno-Flores, Antonio; Potel-Alvarellos, Carmen; Otero-Fernández, Susana; Álvarez-Fernández, Maximiliano

    2017-07-20

    Fluoroquinolone resistance in methicillin-resistant Staphylococcus aureus (MRSA) has increased in recent years. The objective of this study was to characterise two MRSA populations, one susceptible to fluoroquinolones and other resistant identifying the clonal types and the differential characteristics of both MRSA populations. Molecular typing using PFGE, MLST, spa and SSCmec was performed on 192 MRSA strains isolated from 2009 to 2011, 49 only oxacillin-resistant (OX-R) and 143 oxacillin and levofloxacin-resistant (OX-R-LEV-R). Mutations that conferred resistance to fluoroquinolones, hypermutable phenotypes and the presence of eight microbial surface components recognising adhesive matrix molecules (MSCRAMMs) were also studied. A statistically significant increase in the OX-R-LEV-R phenotype was observed (p<0.05). The most common clone of the OX-R isolates was sequence type (ST) 8 (32.6%), followed by ST72 (26.5%) and ST5 (26.5%). In the OX-R-LEV-R phenotype, the ST5 clone was the most common (65.7%), followed by ST72 (15.4%), and ST125 (12.6%). All isolates except the ST398 clone carried the SCCmecIVc. Clones ST5, ST72, ST125, and ST30 had hypermutable phenotypes. The ST72 clone and the ST30 clone in the OX-R phenotype harboured the highest number of MSCRAMMs. ST5 and ST72 clones were the most frequent clones identified in OX-R-LEV-R phenotype. Both clones showed a hypermutable phenotype that favours their selection as the fluoroquinolone resistant clones. The genetic relationships identified indicate that OX-R-LEV-R clones have evolved from OX-R MRSA clones. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  13. Evaluating Fluoroquinolone Use in Patients Admitted to the Tuberculosis Outpatient Clinic

    Directory of Open Access Journals (Sweden)

    Sinem İliaz

    2016-08-01

    Full Text Available Objective: Inelaborate use of new quinolones with strong anti-tuberculosis (TB activity leads to difficulty in diagnosis and more importantly, quinolone-resistant Mycobacterium tuberculosis. We aimed to determine the frequency of quinolone use in patients who were referred to our hospital for suspected TB and to evaluate the association between quinolone use and different clinical laboratory parameters. Methods: Between November 15 and December 15, 2013, all patients who were admitted to the TB outpatient clinic with no previous diagnosis of TB were included in this study. Demographic and clinical laboratory findings and history of antibiotic use were recorded. Patients’ quinolone use were questioned by showing fluoroquinolone antibiotic boxes’ photographs available on the market. The departments of the doctors who prescribed quinolones were recorded. Results: The mean age of 179 patients included in the study was 37±16 (15–89 years. Among these, 113 patients (63.1% were male. Seventy five patients (41.9% were diagnosed as tuberculosis according to the clinical-radiological and/or bacteriological findings. Of 179 patients, 58.1% (n=104 had been prescribed antibiotics for current complaints before referral to our clinic. Sixteen patients (15% had been recommended fluoroquinolones. Fluoroquinolones were prescribed by seven internal medicine specialists, five pulmonologists, three emergency medicine specialists, and one family medicine practitioner. Among 16 fluoroquinolones prescribed, nine were moxifloxacin, four were levofloxacin, and three were gemifloxacin. Quinolone use revealed a significant inverse relationship only with the presence of hemoptysis (p=0.04. Conclusion: Besides increased educational activities regarding the rational use of antibiotics in recent years, the quinolone group of antibiotics is still prescribed for suspected TB cases. To avoid quinolone-resistant M. tuberculosis strains, further education is required.

  14. In vivo degradation behavior and biological activity of some new Mg–Ca alloys with concentration's gradient of Si for bone grafts

    Energy Technology Data Exchange (ETDEWEB)

    Trincă, Lucia Carmen, E-mail: lctrinca@uaiasi.ro [“Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine, Faculty of Horticulture, Str. Aleea M. Sadoveanu, No. 3, 700490 Iasi (Romania); Fântânariu, Mircea, E-mail: mfantanariu@uaiasi.ro [“Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, Str. Aleea M. Sadoveanu, No. 8, 700489 Iasi (Romania); Solcan, Carmen, E-mail: csolcan@yahoo.com [“Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, Str. Aleea M. Sadoveanu, No. 8, 700489 Iasi (Romania); Trofin, Alina Elena, E-mail: aetrofin@yahoo.com [“Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine, Faculty of Horticulture, Str. Aleea M. Sadoveanu, No. 3, 700490 Iasi (Romania); Burtan, Liviu, E-mail: lburtan@uaiasi.ro [“Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, Str. Aleea M. Sadoveanu, No. 8, 700489 Iasi (Romania); Acatrinei, Dumitru Mihai, E-mail: dacatrinei@yahoo.com [“Ion Ionescu de la Brad” University of Agricultural Sciences and Veterinary Medicine, Faculty of Veterinary Medicine, Str. Aleea M. Sadoveanu, No. 8, 700489 Iasi (Romania); Stanciu, Sergiu, E-mail: sergiustanciu2003@yahoo.com [“Gheorghe Asachi” Technical University, Faculty of Materials Science and Engineering, Str. Prof. D. Mangeron, No. 67, 700050 Iasi (Romania); and others

    2015-10-15

    Highlights: • A Mg–Ca alloy with Si concentration gradient was obtained as bone graft material. • Degradation rate of the Mg–Ca–Si alloy was investigated by SEM and EDAX techniques. • Subcutaneous and tibiae implants in rats were monitored by Biochemical, histological, RX and CT investigations monitored implant's evolution. • Si concentration gradient decreased the alloy degradation rate during bone healing. - Abstract: Magnesium based alloys, especially Mg–Ca alloys, are biocompatible substrates with mechanical properties similar to those of bones. The biodegradable alloys of Mg–Ca provide sufficient mechanical strength in load carrying applications as opposed to biopolymers and also they avoid stress shielding and secondary surgery inherent with permanent metallic implant materials. The main issue facing a biodegradable Mg–Ca alloy is the fast degradation in the aggressive physiological environment of the body. The alloy's corrosion is proportional with the dissolution of the Mg in the body: the reaction with the water generates magnesium hydroxide and hydrogen. The accelerated corrosion will lead to early loss of the alloy's mechanical integrity. The degradation rate of an alloy can be improved mainly through tailoring the composition and by carrying out surface treatments. This research focuses on the ability to adjust degradation rate of Mg–Ca alloys by an original method and studies the biological activity of the resulted specimens. A new Mg–Ca alloy, with a Si gradient concentration from the surface to the interior of the material, was obtained. The surface morphology was investigated using scanning electron microscopy (VegaTescan LMH II, SE detector, 30 kV), X-ray diffraction (X’Pert equipment) and energy dispersive X-ray (Bruker EDS equipment). In vivo degradation behavior, biological compatibility and activity of Mg–Ca alloys with/without Si gradient concentration were studied with an implant model (subcutaneous

  15. Jejunal feeding is followed by a greater rise in plasma cholecystokinin, peptide YY, glucagon-like peptide 1, and glucagon-like peptide 2 concentrations compared with gastric feeding in vivo in humans

    DEFF Research Database (Denmark)

    Luttikhold, Joanna; van Norren, Klaske; Rijna, Herman

    2016-01-01

    and the associated endocrine response in vivo in humans remains largely unexplored. OBJECTIVE: We compared the impact of administering enteral nutrition as either gastric feeding or jejunal feeding on endocrine responses in vivo in humans. DESIGN: In a randomized, crossover study design, 12 healthy young men (mean...... and a greater postprandial incremental AUC for GLP-1 and cholecystokinin (all P young men results in similar postprandial plasma amino acid and glucose concentrations....... However, the endocrine response differs substantially, with higher peak plasma cholecystokinin, PYY, GLP-1, and GLP-2 concentrations being attained after jejunal feeding. This effect may result in an improved anabolic response, greater insulin sensitivity, and an improved intestinotropic effect...

  16. Pyrosequencing for Rapid Detection of Mycobacterium tuberculosis Resistance to Rifampin, Isoniazid, and Fluoroquinolones

    Science.gov (United States)

    Bravo, Lulette Tricia C.; Tuohy, Marion J.; Ang, Concepcion; Destura, Raul V.; Mendoza, Myrna; Procop, Gary W.; Gordon, Steven M.; Hall, Geraldine S.; Shrestha, Nabin K.

    2009-01-01

    After isoniazid and rifampin (rifampicin), the next pivotal drug class in Mycobacterium tuberculosis treatment is the fluoroquinolone class. Mutations in resistance-determining regions (RDR) of the rpoB, katG, and gyrA genes occur with frequencies of 97%, 50%, and 85% among M. tuberculosis isolates resistant to rifampin, isoniazid, and fluoroquinolones, respectively. Sequences are highly conserved, and certain mutations correlate well with phenotypic resistance. We developed a pyrosequencing assay to determine M. tuberculosis genotypic resistance to rifampin, isoniazid, and fluoroquinolones. We characterized 102 M. tuberculosis clinical isolates from the Philippines for susceptibility to rifampin, isoniazid, and ofloxacin by using the conventional submerged-disk proportion method and validated our pyrosequencing assay using these isolates. DNA was extracted and amplified by using PCR primers directed toward the RDR of the rpoB, katG, and gyrA genes, and pyrosequencing was performed on the extracts. The M. tuberculosis H37Rv strain (ATCC 25618) was used as the reference strain. The sensitivities and specificities of pyrosequencing were 96.7% and 97.3%, 63.8% and 100%, and 70.0% and 100% for the detection of resistance to rifampin, isoniazid, and ofloxacin, respectively. Pyrosequencing is thus a rapid and accurate method for detecting M. tuberculosis resistance to these three drugs. PMID:19846642

  17. Frequent topoisomerase IV mutations associated with fluoroquinolone resistance in Ureaplasma species.

    Science.gov (United States)

    Song, Jingjuan; Qiao, Yingli; Kong, Yingying; Ruan, Zhi; Huang, Jun; Song, Tiejun; Zhang, Jun; Xie, Xinyou

    2015-11-01

    This study aimed to investigate the role of quinolone resistance-determining regions (QRDRs) of DNA gyrase (encoded by gyrA and gyrB) and topoisomerase IV (encoded by parC and parE) associated with fluoroquinolone resistance. A total of 114 Ureaplasma spp. strains, isolated from clinical female patients with symptomatic infection, were tested for species distribution and susceptibility to four fluoroquinolones. Moreover, we analysed the QRDRs and compared these with 14 ATCC reference strains of Ureaplasma spp. serovars to identify mutations that caused antimicrobial resistance. Our study indicated that moxifloxacin was the most effective fluoroquinolone against Ureaplasma spp. (MIC range: 0.125-32 μg ml⁻¹). However, extremely high MICs were estimated for ciprofloxacin (MIC range: 1-256 μg ml⁻¹) and ofloxacin (MIC range: 0.5-128 μg ml⁻¹), followed by levofloxacin (MIC range: 0.5-64 μg ml⁻¹). Seven amino acid substitutions were discovered in GyrB, ParC and ParE, but not in GyrA. Ser-83 → Leu/Trp (C248T/G) in ParC and Arg-448 → Lys (G1343A) in ParE, which were potentially responsible for fluoroquinolone resistance, were observed in 89 (77.2 %) and three (2.6 %) strains, respectively. Pro-462 → Ser (C1384T), Asn-481 → Ser (A1442G) and Ala-493 → Val (C1478T) in GyrB and Met-105 → Ile (G315T) in ParC seemed to be neutral polymorphisms, and were observed and occurred along with the amino acid change of Ser-83 → Leu (C248T) in ParC. Interestingly, two novel mutations of ParC and ParE were independently found in four strains. These observations suggest that amino acid mutation in topoisomerase IV appears to be the leading cause of fluoroquinolone resistance, especially the mutation of Ser-83 → Leu (C248T) in ParC. Moxifloxacin had the best activity against strains with Ser-83 → Leu mutation.

  18. The effect of two bleaching agents on the phosphate concentration of the enamel evaluated by Raman spectroscopy: An ex vivo study

    Directory of Open Access Journals (Sweden)

    Sokkalingam Mothilal Venkatesan

    2012-01-01

    Full Text Available Aim : The aim of this ex vivo study was to evaluate the effect of in-office bleaching agents,-35% and 38% hydrogen peroxide containing bleaching agents, on the phosphate concentration of the enamel evaluated by Raman spectroscopy. Materials and Methods : Forty noncarious, craze-free human maxillary incisors, extracted for periodontal reasons, were used in this study. Baseline Raman spectra from each specimen were obtained before the application of the bleaching agent to assess the phosphate content present in the teeth. The teeth were divided into two groups: Group A - bleached with pola office bleach (35% hydrogen peroxide, potassium nitrate (light activated. Group B - bleached with opalescence Xtra bleach (38% hydrogen peroxide potassium nitrate and fluoride (chemical activated. After the bleaching procedure, the treated specimens were taken to obtain Raman spectra to assess the phosphate loss after bleaching treatment. Results : The results showed that the chemically activated bleaching agent showed less phosphate loss when compared with the light activated bleaching agent. Conclusion : Within the limitations of this study, it can be concluded that the chemically activated bleaching agent showed minimal phosphate loss when compared to light activated bleaching agent. The chemically activated bleaching agent was better than the light activated bleaching agent when values were evaluated statistically.

  19. Effect of exercise on erythrocyte count and blood activity concentration after /sup 99m/Tc in vivo red blood cell labeling

    International Nuclear Information System (INIS)

    Konstam, M.A.; Tu'meh, S.; Wynne, J.; Beck, J.R.; Kozlowski, J.; Holman, B.L.

    1982-01-01

    We studied the effect of exercise on blood radiotracer concentration after /sup 99m/Tc in vivo red blood cell labeling. After red blood cell labeling, 13 subjects underwent maximal supine bicycle exercise. Radioactivity, analyzed with a well counter, was measured in heparinized venous blood samples drawn at rest and during peak exercise. Changes in activity were compared with changes in erythrocyte count. Activity and erythrocyte counts increased during exercise in all 13 subjects. Percent increase in activity correlated with percent increase in erythrocyte count (r . -0.78), but did not correlate with either duration of exercise or maximal heart rate. Twenty minutes after termination of exercise, activity and erythrocyte count had decreased from peak exercise values but remained higher than preexercise values. In nine nonexercised control subjects, samples drawn 20 minutes apart showed no change in activity or in erythrocyte count. We conclude that exercise increases blood activity, primarily because of an increase in erythrocyte count. During radionuclide ventriculography, blood activity must be measured before and after any intervention, particularly exercise, before a change in left ventricular activity can be attributed to a change in left ventricular volume

  20. Altered Expression of Somatostatin Receptors in Pancreatic Islets from NOD Mice Cultured at Different Glucose Concentrations In Vitro and in Islets Transplanted to Diabetic NOD Mice In Vivo

    Directory of Open Access Journals (Sweden)

    Eva Ludvigsen

    2011-01-01

    Full Text Available Somatostatin acts via five receptors (sst1-5. We investigated if the changes in pancreatic islet sst expression in diabetic NOD mice compared to normoglycemic mice are a consequence of hyperglycemia or the ongoing immune reaction in the pancreas. Pancreatic islets were isolated from NOD mice precultured for 5 days and further cultured for 3 days at high or low glucose before examined. Islets were also isolated from NOD mice and transplanted to normal or diabetic mice in a number not sufficient to cure hyperglycemia. After three days, the transplants were removed and stained for sst1-5 and islet hormones. Overall, changes in sst islet cell expression were more common in islets cultured in high glucose concentration in vitro as compared to the islet transplantation in vivo to diabetic mice. The beta and PP cells exhibited more frequent changes in sst expression, while the alpha and delta cells were relatively unaffected by the high glucose condition. Our findings suggest that the glucose level may alter sst expressed in islets cells; however, immune mechanisms may counteract such changes in islet sst expression.

  1. In vitro susceptibilities to fluoroquinolones in current and archived Mycoplasma gallisepticum and Mycoplasma synoviae isolates from meat-type turkeys.

    Science.gov (United States)

    Gerchman, Irina; Lysnyansky, Inna; Perk, Shimon; Levisohn, Sharon

    2008-10-15

    Monitoring of susceptibility to antibiotics in field isolates of pathogenic avian mycoplasmas is important for appropriate choice of treatment. Our study compared in vitro susceptibility to enrofloxacin and difloxacin in recent (2005-2006) isolates of Mycoplasma gallisepticum and Mycoplasma synoviae from meat-type turkey flocks with archived (1997-2003) isolates and reference strains. Comparison of minimal inhibitory concentration (MIC) values determined by microtest, agar dilution and commercial Etest showed good agreement, but underscored the need for standardized methods for testing. Notably, while the commercial Etest was convenient and accurate for determining MICs for enrofloxacin in the range 0.002-0.094microg/ml, the endpoint of inhibition for M. gallisepticum and M. synoviae strains with MIC values > or =1.0microg/ml could not be determined. A decrease in susceptibility to both fluoroquinolones was detected in archived strains but to a greater degree in recent isolates, most of which had MICs above the NCCLS susceptibility breakpoint for these antibiotics (meat-type turkeys suggests that these strains have become established in Israel, necessitating a reevaluation of antibiotic therapy. Periodic survey of MICs in field isolates of avian mycoplasmas to monitor for the possible appearance of resistant strains is recommended.

  2. Study of the interactions between fluoroquinolones and human serum albumin by affinity capillary electrophoresis and fluorescence method

    International Nuclear Information System (INIS)

    Zhang Liwei; Wang Kun; Zhang Xinxiang

    2007-01-01

    The interactions between fluoroquinolones and human serum albumin (HSA) were investigated by affinity capillary electrophoresis (ACE) and fluorescence quenching technique. Based on the efficient separation of several fluoroquinolones using a simple phosphate buffer, the binding constants of fluoroquinolones with HSA were determined simultaneously during one set of electrophoresis by ACE method. The thermodynamic parameters were obtained from data at different temperatures, and the negative ΔH and ΔS values showed that both hydrogen bonds and van der Waals interaction played major roles in the binding of fluoroquinolones to HSA. The interactions were also studied by fluorescence quenching technique. The results of fluorescence titration revealed that fluoroquinolones had the strong ability to quenching the intrinsic fluorescence of HSA through the static quenching procedure. The binding site number n, apparent binding constant K b and the Stern-Volmer quenching constant K sv were determined. The thermodynamic parameters were also studied by fluorescence method, and the results were consonant with that of ACE

  3. Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection.

    Science.gov (United States)

    Shea, Katherine M; Hobbs, Athena L V; Jaso, Theresa C; Bissett, Jack D; Cruz, Christopher M; Douglass, Elizabeth T; Garey, Kevin W

    2017-06-01

    Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system. Copyright © 2017 American Society for Microbiology.

  4. Global Phenotypic Characterization of Effects of Fluoroquinolone Resistance Selection on the Metabolic Activities and Drug Susceptibilities of Clostridium perfringens Strains

    Directory of Open Access Journals (Sweden)

    Miseon Park

    2014-01-01

    Full Text Available Fluoroquinolone resistance affects toxin production of Clostridium perfringens strains differently. To investigate the effect of fluoroquinolone resistance selection on global changes in metabolic activities and drug susceptibilities, four C. perfringens strains and their norfloxacin-, ciprofloxacin-, and gatifloxacin-resistant mutants were compared in nearly 2000 assays, using phenotype microarray plates. Variations among mutant strains resulting from resistance selection were observed in all aspects of metabolism. Carbon utilization, pH range, osmotic tolerance, and chemical sensitivity of resistant strains were affected differently in the resistant mutants depending on both the bacterial genotype and the fluoroquinolone to which the bacterium was resistant. The susceptibilities to gentamicin and erythromycin of all resistant mutants except one increased, but some resistant strains were less susceptible to amoxicillin, cefoxitin, ceftriaxone, chloramphenicol, and metronidazole than their wild types. Sensitivity to ethidium bromide decreased in some resistant mutants and increased in others. Microarray analysis of two gatifloxacin-resistant mutants showed changes in metabolic activities that were correlated with altered expression of various genes. Both the chemical structures of fluoroquinolones and the genomic makeup of the wild types influenced the changes found in resistant mutants, which may explain some inconsistent reports of the effects of therapeutic use of fluoroquinolones on clinical isolates of bacteria.

  5. Antimicrobial resistance (AMR) nanomachines-mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation.

    Science.gov (United States)

    Phillips-Jones, Mary K; Harding, Stephen E

    2018-04-01

    In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics-the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that

  6. evaluation of some technetium-99m fluoroquinolones complexes as imaging agents for bacterial inflammatory lesions

    International Nuclear Information System (INIS)

    Abdel-Kawy, O.A.A.

    2007-01-01

    in this study, the labeling method of ciprofloxacin and levofloxacin with technetium-99m and their biological evaluation in man-induced inflammation models were described . in -vitro microbiological evaluation of both complexes was also performed in order to investigate the effect of labeling on the activity and spectrum of both antibiotics. all the gathered biological data support the usefulness of 99m Tc-fluoroquinolones as infection imaging agents that could discriminate between infections and sterile inflammations. the freeze-dried form of levofloxacin kits was prepared and found to meet all the radiochemical and biological tests

  7. Fluoroquinolone-Resistant Escherichia coli Infections after Transrectal Biopsy of the Prostate in the Veterans Affairs Healthcare System

    Directory of Open Access Journals (Sweden)

    Elie Antoun Saade

    2016-09-01

    Full Text Available Background: Recent reports suggest that infections due to fluoroquinolone-resistant Escherichia coli (E. coli are an increasingly common complication of transrectal biopsy of the prostate (TBP in the United States. A better understanding of the magnitude and scope of these infections is needed to guide prevention efforts. Our objective is to determine whether the incidence of infections due to fluoroquinolone-resistant E. coli after TBP has increased nationwide in the Veterans Affairs Health Care System and to identify risk factors for infection. Methods: We performed a retrospective, observational cohort study and a nested case-control study within the US Deparment of Veterans Affairs Healthcare System. The primary outcomes were the incidence of urinary tract infection (UTI and bacteremia with E. coli and with fluoroquinolone-resistant E. coli strains within 30 days after TBP. Secondary endpoints focused on the correlation between fluoroquinolone-resistance in all urinary E. coli isolates and post-TBP infection and risk factors for infection due to fluoroquinolone-resistant E. coli infection. Results: 245 618 patients undergoing 302 168 TBP procedures from 2000 through 2013 were included in the cohort study, and 59 469 patients undergoing TBP from 2011 through 2013 were included in the nested case-control study. Between 2000 and 2013, there was a 5-fold increase in the incidence of E. coli UTI (0.18%–0.93% and a 4-fold increase in the incidence of E. coli bacteremia (0.04%–0.18% after TBP that was attributable to an increase in the incidence of fluoroquinolone-resistant E. coli UTI (0.03%–0.75% and bacteremia (0.01%–0.14%. The increasing incidence of fluoroquinolone-resistant E. coli infections after TBP occurred in parallel with increasing rates of fluoroquinolone-resistance in all urinary E. coli isolates. By multivariable logistic regression analysis, independent risk factors for fluoroquinolone

  8. Intravenous piperacillin/tazobactam plus fluoroquinolone prophylaxis prior to prostate ultrasound biopsy reduces serious infectious complications and is cost effective

    Directory of Open Access Journals (Sweden)

    Remynse LC

    2011-08-01

    Full Text Available Louis C Remynse III, Patrick J Sweeney, Kevin A Brewton, Jay M LonswayUrology Associates of Battle Creek, PC, Battle Creek, MI, USAAbstract: Infectious complications related to prostate ultrasound and biopsy have increased in the past decade with the emergence of increasing fluoroquinolone bacterial resistance. We investigated the addition of intravenous (iv piperacillin/tazobactam immediately prior to prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis to determine if it would decrease the incidence of serious infectious complications after prostate ultrasound and biopsy. Group 1 patients were a historic control of 197 patients who underwent prostate ultrasound and biopsy with standard fluoroquinolone prophylaxis. Group 2 patients, 104 patients, received standard fluoroquinolone prophylaxis and the addition of a single dose of iv piperacillin/tazobactam 30 minutes prior to prostate ultrasound and biopsy. There were ten serious bacterial infectious complications in group 1 patients. No patients in group 2 developed serious bacterial infections after prostate ultrasound and biopsy. There was approximately a 5% incidence of serious bacterial infection in group 1 patients. Subgroup analysis revealed an almost 2.5 times increased risk of infection in diabetes patients undergoing prostate ultrasound and biopsy. There was a 10% risk of serious bacterial infection in diabetics compared with a 3.8% risk group 1 nondiabetes patients. The addition of a single dose of iv piperacillin/tazobactam along with standard fluoroquinolone prophylaxis substantially reduces the risk of serious bacterial infection after prostate ultrasound and biopsy (P < 0.02.Keywords: piperacillin/tazobactam, fluoroquinolone, prostate biopsy, infectious complications

  9. Starvation, Together with the SOS Response, Mediates High Biofilm-Specific Tolerance to the Fluoroquinolone Ofloxacin

    Science.gov (United States)

    Bernier, Steve P.; Lebeaux, David; DeFrancesco, Alicia S.; Valomon, Amandine; Soubigou, Guillaume; Coppée, Jean-Yves; Ghigo, Jean-Marc; Beloin, Christophe

    2013-01-01

    High levels of antibiotic tolerance are a hallmark of bacterial biofilms. In contrast to well-characterized inherited antibiotic resistance, molecular mechanisms leading to reversible and transient antibiotic tolerance displayed by biofilm bacteria are still poorly understood. The physiological heterogeneity of biofilms influences the formation of transient specialized subpopulations that may be more tolerant to antibiotics. In this study, we used random transposon mutagenesis to identify biofilm-specific tolerant mutants normally exhibited by subpopulations located in specialized niches of heterogeneous biofilms. Using Escherichia coli as a model organism, we demonstrated, through identification of amino acid auxotroph mutants, that starved biofilms exhibited significantly greater tolerance towards fluoroquinolone ofloxacin than their planktonic counterparts. We demonstrated that the biofilm-associated tolerance to ofloxacin was fully dependent on a functional SOS response upon starvation to both amino acids and carbon source and partially dependent on the stringent response upon leucine starvation. However, the biofilm-specific ofloxacin increased tolerance did not involve any of the SOS-induced toxin–antitoxin systems previously associated with formation of highly tolerant persisters. We further demonstrated that ofloxacin tolerance was induced as a function of biofilm age, which was dependent on the SOS response. Our results therefore show that the SOS stress response induced in heterogeneous and nutrient-deprived biofilm microenvironments is a molecular mechanism leading to biofilm-specific high tolerance to the fluoroquinolone ofloxacin. PMID:23300476

  10. Determination of residual fluoroquinolones in honey by liquid chromatography using metal chelate affinity chromatography.

    Science.gov (United States)

    Yatsukawa, Yoh-Ichi; Ito, Hironobu; Matsuda, Takahiro; Nakamura, Munetomo; Watai, Masatoshi; Fujita, Kazuhiro

    2011-01-01

    A new analytical method for the simultaneous determination of seven fluoroquinolones, namely, norfloxacin, ciprofloxacin, danofloxacin, enrofloxacin, orbifloxacin, sarafloxacin, and difloxacin, especially in dark-colored honey, has been developed. Fluoroquinolone antibiotics were extracted from samples with MacIlvaine buffer solution (pH 4.0) containing EDTA disodium salt dihydrate. The extracts were treated with both a polymeric cartridge and a metal chelate affinity column preloaded with ferric ion (Fe3+). LC separation with fluorescence detection was performed at 40 degrees C using an Inertsil ODS-4 analytical column (150 x 4.6 mm, 3 microm). The mobile phase was composed of 20 mM/L citrate buffer solution (pH 3.1)-acetonitrile mixture (70 + 30, v/v) containing 1 mM/L sodium dodecyl sulfate. Lomefloxacin was used as an internal standard. The developed method was validated according to the criteria of European Commission Decision 2002/657/EC. Decision limits and detection capabilities were below 2.9 and 4.4 microg/kg, respectively.

  11. In vitro activity of fluoroquinolones (gatifloxacin, levofloxacin and trovafloxacin and seven other antibiotics against Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Nicodemo A.C.

    2001-01-01

    Full Text Available In recent years, the level of resistance of S. pneumoniae to beta-lactam and/or macrolides has increased around the world including some countries in South America. Because of this resistance, it is necessary to test the therapeutic alternatives for treating this pathogen, including the newer quinolones. This study was carried out in order to compare the in vitro activity of fluoroquinolones gatifloxacin, levofloxacin and trovafloxacin, to penicillin G, amoxicillin, amoxicillin-clavulanate, cufuroxime sodium, ceftriaxone, azithromycin and clarithromycin, against 300 strains of S. pneumoniae. Of the 300 samples tested, 18.6% were not susceptible to penicillin (56 strains and 7% (21 strains were resistant to the second generation cephalosporin. Among the macrolides, resistance ranged from 6.7% for clarithromycin to 29.6% for azithromycin. Susceptibility to the newer quinolones was 100% including the 56 strains not susceptible to penicillin. Among the 10 antibiotics evaluated, the fluoroquinolones gatifloxacin, levofloxacin, and trovafloxacin displayed high levels of in vitro activity against S. pneumoniae.

  12. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

    Science.gov (United States)

    Oh, Euna; Jeon, Byeonghwa

    2015-01-01

    The increasing resistance of Campylobacter to clinically important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN). Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux. PMID:26528273

  13. Gemifloxacin, a Fluoroquinolone Antimicrobial Drug, Inhibits Migration and Invasion of Human Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jung-Yu Kan

    2013-01-01

    Full Text Available Gemifloxacin (GMF is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT. In addition, GMF suppresses the activation of NF-κB and cell migration and invasion induced by TNF-α and inhibits the TAK1/TAB2 interaction, resulting in decreased IκB phosphorylation and NF-κB nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.

  14. Follicular 17β-estradiol and progesterone concentrations and degree of cumulus cell expansion as predictors of in vivo-matured oocyte developmental competence in superstimulated heifers

    NARCIS (Netherlands)

    Aardema, Hilde; Roelen, Bernard A J; van Tol, Helena T A; Oei, Christine H Y; Gadella, Bart M; Vos, Peter L A M

    2013-01-01

    The quality of an oocyte is crucial for successful generation of offspring, but few selection parameters have been identified that reliably predict oocyte developmental competence. The objective of the present study was to determine whether the developmental competence of in vivo-matured oocytes

  15. Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones

    NARCIS (Netherlands)

    Chau, Tran Thuy; Campbell, James Ian; Galindo, Claudia M.; van Minh Hoang, Nguyen; Diep, To Song; Nga, Tran Thu Thi; van Vinh Chau, Nguyen; Tuan, Phung Quoc; Page, Anne Laure; Ochiai, R. Leon; Schultsz, Constance; Wain, John; Bhutta, Zulfiqar A.; Parry, Christopher M.; Bhattacharya, Sujit K.; Dutta, Shanta; Agtini, Magdarina; Dong, Baiqing; Honghui, Yang; Anh, Dang Duc; Canh, Do Gia; Naheed, Aliya; Albert, M. John; Phetsouvanh, Rattanaphone; Newton, Paul N.; Basnyat, Buddha; Arjyal, Amit; La, Tran Thi Phi; Rang, Nguyen Ngoc; Phuong, Le Thi; van Be Bay, Phan; von Seidlein, Lorenz; Dougan, Gordon; Clemens, John D.; Vinh, Ha; Hien, Tran Tinh; Chinh, Nguyen Tran; Acosta, Camilo J.; Farrar, Jeremy; Dolecek, Christiane

    2007-01-01

    This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar

  16. 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

  17. Prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy: A prospective multicenter study.

    Science.gov (United States)

    Chung, Ho Seok; Hwang, Eu Chang; Yu, Ho Song; Jung, Seung Il; Lee, Sun Ju; Lim, Dong Hoon; Cho, Won Jin; Choe, Hyun Sop; Lee, Seung-Ju; Park, Sung Woon

    2018-03-01

    To estimate the prevalence of fluoroquinolone-resistant rectal flora in patients undergoing transrectal ultrasound-guided prostate needle biopsy and to identify the high-risk groups. From January 2015 to March 2016, rectal swabs of 557 men who underwent transrectal ultrasound-guided prostate needle biopsy were obtained from five institutions. Clinical variables, including demographics, rectal swab culture results and infectious complications, were evaluated. Univariable and multivariable analyses were used to identify the risk factors for fluoroquinolone resistance of rectal flora and infectious complications. The incidence of fluoroquinolone-resistant and extended-spectrum beta-lactamase production was 48.1 and 11.8%, respectively. The most common fluoroquinolone-resistant bacteria was Escherichia coli (81% of total fluoroquinolone-resistant bacteria, 39% of total rectal flora), and 16 (2.9%) patients had infectious complications. Univariable and multivariable analysis of clinical parameters affecting fluoroquinolone resistance showed no factor associated with fluoroquinolone resistance of rectal flora. The clinical parameter related to infectious complications after prostate biopsy was a history of operation within 6 months (relative risk 6.60; 95% confidence interval 1.99-21.8, P = 0.002). These findings suggest that a risk-based approach by history taking cannot predict antibiotic resistance of rectal flora, and physicians should consider targeted antibiotic prophylaxis or extended antibiotic prophylaxis for Korean patients undergoing transrectal ultrasound-guided prostate biopsy because of high antibiotic resistance of rectal flora. © 2017 The Japanese Urological Association.

  18. Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia

    Science.gov (United States)

    Wang, Chi-Chuan; Lin, Chia-Hui; Lin, Kuan-Yin; Chuang, Yu-Chung; Sheng, Wang-Huei

    2016-01-01

    Abstract Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to β-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics. This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups. After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77–0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92–1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30–1.62) between the 2 groups. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted. PMID:26871827

  19. Successful outcomes with oral fluoroquinolones combined with rifampicin in the treatment of Mycobacterium ulcerans: an observational cohort study.

    Directory of Open Access Journals (Sweden)

    Daniel P O'Brien

    2012-01-01

    Full Text Available BACKGROUND: The World Health Organization currently recommends combined streptomycin and rifampicin antibiotic treatment as first-line therapy for Mycobacterium ulcerans infections. Alternatives are needed when these are not tolerated or accepted by patients, contraindicated, or neither accessible nor affordable. Despite in vitro effectiveness, clinical evidence for fluoroquinolone antibiotic use against Mycobacterium ulcerans is lacking. We describe outcomes and tolerability of fluoroquinolone-containing antibiotic regimens for Mycobacterium ulcerans in south-eastern Australia. METHODOLOGY/PRINCIPAL FINDINGS: Analysis was performed of prospectively collected data including all primary Mycobacterium ulcerans infections treated at Barwon Health between 1998 and 2010. Medical treatment involved antibiotic use for more than 7 days; surgical treatment involved surgical excision of a lesion. Treatment success was defined as complete lesion healing without recurrence at 12 months follow-up. A complication was defined as an adverse event attributed to an antibiotic that required its cessation. A total of 133 patients with 137 lesions were studied. Median age was 62 years (range 3-94 years. 47 (34% had surgical treatment alone, and 90 (66% had combined surgical and medical treatment. Rifampicin and ciprofloxacin comprised 61% and rifampicin and clarithromycin 23% of first-line antibiotic regimens. 13/47 (30% treated with surgery alone failed treatment compared to 0/90 (0% of those treated with combination medical and surgical treatment (p<0.0001. There was no difference in treatment success rate for antibiotic combinations containing a fluoroquinolone (61/61 cases; 100% compared with those not containing a fluoroquinolone (29/29 cases; 100%. Complication rates were similar between ciprofloxacin and rifampicin (31% and rifampicin and clarithromycin (33% regimens (OR 0.89, 95% CI 0.27-2.99. Paradoxical reactions during treatment were observed in 8 (9% of

  20. Fatal embryo chondral damage associated with fluoroquinolones in eggs of threatened avian scavengers

    International Nuclear Information System (INIS)

    Lemus, J.A.; Blanco, G.; Arroyo, B.; Martinez, F.; Grande, J.

    2009-01-01

    Stabled livestock reared in housed conditions are often subjected to intensive treatments with veterinary drug, which residues may be present in livestock meat ingested by scavengers, but nothing is known about their presence in eggs of wild birds and their potential detrimental effects on breeding success. We searched for residues of veterinary drugs and other toxicants in infertile and embryonated unhatched eggs of griffon vultures (Gyps fulvus) and red kites (Milvus milvus), two threatened avian scavengers. Quinolones (ciprofloxacin and enrofloxacin) were found in most unhatched eggs of both scavenger species clearly associated with severe alterations in the development of embryo cartilage and bones that could preclude embryo movements and subsequently normal development, pre-hatch position and successful hatching. The detrimental effects on developing eggs of veterinary drugs from livestock operations may help to explain reduced breeding success of avian scavengers. - Fluoroquinolones used in livestock farming and found in eggs of avian scavenger caused severe alterations in embryo cartilage and bone development.

  1. Fatal embryo chondral damage associated with fluoroquinolones in eggs of threatened avian scavengers

    Energy Technology Data Exchange (ETDEWEB)

    Lemus, J.A. [Departamento de Ecologia Evolutiva, Museo Nacional de Ciencias Naturales (CSIC), J. Gutierrez Abascal 2, 28006 Madrid (Spain); Blanco, G., E-mail: gublanco2@yahoo.e [Departamento de Ecologia Evolutiva, Museo Nacional de Ciencias Naturales (CSIC), J. Gutierrez Abascal 2, 28006 Madrid (Spain); Arroyo, B.; Martinez, F.; Grande, J. [Departamento de Ecologia Evolutiva, Museo Nacional de Ciencias Naturales (CSIC), J. Gutierrez Abascal 2, 28006 Madrid (Spain)

    2009-08-15

    Stabled livestock reared in housed conditions are often subjected to intensive treatments with veterinary drug, which residues may be present in livestock meat ingested by scavengers, but nothing is known about their presence in eggs of wild birds and their potential detrimental effects on breeding success. We searched for residues of veterinary drugs and other toxicants in infertile and embryonated unhatched eggs of griffon vultures (Gyps fulvus) and red kites (Milvus milvus), two threatened avian scavengers. Quinolones (ciprofloxacin and enrofloxacin) were found in most unhatched eggs of both scavenger species clearly associated with severe alterations in the development of embryo cartilage and bones that could preclude embryo movements and subsequently normal development, pre-hatch position and successful hatching. The detrimental effects on developing eggs of veterinary drugs from livestock operations may help to explain reduced breeding success of avian scavengers. - Fluoroquinolones used in livestock farming and found in eggs of avian scavenger caused severe alterations in embryo cartilage and bone development.

  2. Increasing incidence of fluoroquinolone-resistant Mycobacterium tuberculosis in Mumbai, India.

    Science.gov (United States)

    Agrawal, D; Udwadia, Z F; Rodriguez, C; Mehta, A

    2009-01-01

    Tertiary referral centre, private hospital, Mumbai, India. To analyse the incidence of fluoroquinolone (FQ) resistant Mycobacterium tuberculosis (TB) in our laboratory from 1995 to 2004. Retrospective review and analysis of the drug susceptibility test records of all M. tuberculosis culture-positive samples from our Microbiology Department from 1995 to 2004. FQ resistance has increased exponentially in our laboratory, from 3% in 1996 to 35% in 2004. The incidence of multidrug-resistant tuberculosis has also increased during the same period, from 33% in 1995 to 56% in 2004. The incidence of FQ-resistant M. tuberculosis is gradually increasing to alarming levels. This may be due to widespread use of this vital group of drugs in the treatment of community-acquired infections. We urge that these broad spectrum antibiotics be used judiciously, and ideally be reserved for treatment of resistant TB in TB-endemic areas.

  3. Fluoroquinolone-resistant Escherichia coli carriage in long-term care facility.

    Science.gov (United States)

    Maslow, Joel N; Lee, Betsy; Lautenbach, Ebbing

    2005-06-01

    We conducted a cross-sectional study to determine the prevalence of, and risk factors for, colonization with fluoroquinolone (FQ)-resistant Escherichia coli in residents in a long-term care facility. FQ-resistant E. coli were identified from rectal swabs for 25 (51%) of 49 participants at study entry. On multivariable analyses, prior FQ use was the only independent risk factor for FQ-resistant E. coli carriage and was consistent for FQ exposures in the previous 3, 6, 9, or 12 months. Pulsed-field gel electrophoresis of FQ-resistant E. coli identified clonal spread of 1 strain among 16 residents. Loss (6 residents) or acquisition (7 residents) of FQ-resistant E. coli was documented and was associated with de novo colonization with genetically distinct strains. Unlike the case in the hospital setting, FQ-resistant E. coli carriage in long-term care facilities is associated with clonal spread.

  4. Fluoroquinolones (FQs) in the environment: A review on their abundance, sorption and toxicity in soil.

    Science.gov (United States)

    Riaz, Luqman; Mahmood, Tariq; Khalid, Azeem; Rashid, Audil; Ahmed Siddique, Muhammad Bashir; Kamal, Atif; Coyne, Mark S

    2018-01-01

    The use of fluoroquinolones (FQs) antibiotics as therapeutic agents and growth promoters is increasing worldwide; however their extensive uses are also resulting in antibiotic resistance among world communities. FQs have also become one of the major contaminants in the waste water bodies, which are not even completely removed during the treatment processes. Furthermore, their abundance in agricultural resources, such as the irrigation water, the bio-solids and the livestock manure can also affect the soil micro-environment. These antibiotics in soil tend to interact in several different ways to affect soil flora and fauna. The current review endeavors to highlight the some critical aspects of FQs prevalence in the environment. The review presents a detailed discussion on the pathways and abundance of FQs in soil. The discussion further spans the issue of sorption and FQs transformation into the soil better understand of their behavior and their toxicity to soil flora and fauna. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. National antimicrobial stewardship and fluoroquinolone-resistant Clostridium difficile in China

    Directory of Open Access Journals (Sweden)

    Xiao M

    2017-10-01

    Full Text Available Meng Xiao,1,* Jing-Wei Cheng,1,2,* Timothy Kudinha,3 Fanrong Kong,4 Ying-Chun Xu1,21Department of Clinical Laboratory, Peking Union Medical College Hospital, 2Faculty of Clinical Laboratory Diagnostics, Graduate School, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China; 3School of Biomedical Sciences, The Charles Sturt University, Leeds Parade, Orange, 4Centre for Infectious Diseases and Microbiology Laboratory Services, ICPMR–Pathology West, Westmead Hospital, University of Sydney, Westmead, NSW, Australia*These authors contributed equally to this workIn a recent report, Dingle et al showed that national intervention programs aimed at judicious antimicrobial usage, especially restrictions to fluoroquinolones, contributed to a significant decrease in Clostridium difficile infection (CDI in England.1 This is considered an outstanding achievement in combating antimicrobial resistance worldwide.

  6. Comparative clinical study of conjunctival toxicities of newer generation fluoroquinolones without the influence of preservatives

    Directory of Open Access Journals (Sweden)

    Han Sang Park

    2015-12-01

    Full Text Available To compare the conjunctival epithelial toxicities of three newer-generation fluoroquinolones without preservatives. In a prospective, randomized, double blind comparative study, 47 eyes of 47 patients with a primary pterygium were enrolled, and divided randomly into three groups (levofloxacin 0.5%, gatifloxacin 0.3%, and moxifloxacin 0.5%. After pterygium surgery with the same conjunctival autograft technique, each patient maintained a regimen with a randomly assigned fluoroquinolone eye drop. Patients were examined every other day after surgery until the epithelium had completely healed. Photos were taken and used to measure the area of residual epithelial defects. Conjunctival healing time and speed (initial defect area/healing time (mm2/d compared in each group using Kruskal-Wallis tests. There were no significant differences in mean age, gender, and conjunctival defect size of the donor site between these groups. However, the mean of conjunctival healing time and speed were statistically different in each group. The mean of conjunctival epithelial healing time was 8.93±2.69d (levofloxacin group, 10.31±2.96d (gatifloxacin group, and 13.50±4.10d (moxifloxacin group, P=0.006. The mean conjuctival epithelial healing speed was 6.18±1.39 mm2/d (levofloxacin group, 5.52±1.68 mm2/d (gatifloxacin group, and 4.40±1.30 mm2/d (moxifloxacin group, P=0 .003. Without the influence of preservatives, levofloxacin and gatifloxacin might be less toxic to the regeneration of conjunctival epithelial cells and cause a faster conjunctival wound healing relative to moxifloxacin.

  7. Pleiotropic Effects of Levofloxacin, Fluoroquinolone Antibiotics, against Influenza Virus-Induced Lung Injury.

    Directory of Open Access Journals (Sweden)

    Yuki Enoki

    Full Text Available Reactive oxygen species (ROS and nitric oxide (NO are major pathogenic molecules produced during viral lung infections, including influenza. While fluoroquinolones are widely used as antimicrobial agents for treating a variety of bacterial infections, including secondary infections associated with the influenza virus, it has been reported that they also function as anti-oxidants against ROS and as a NO regulator. Therefore, we hypothesized that levofloxacin (LVFX, one of the most frequently used fluoroquinolone derivatives, may attenuate pulmonary injuries associated with influenza virus infections by inhibiting the production of ROS species such as hydroxyl radicals and neutrophil-derived NO that is produced during an influenza viral infection. The therapeutic impact of LVFX was examined in a PR8 (H1N1 influenza virus-induced lung injury mouse model. ESR spin-trapping experiments indicated that LVFX showed scavenging activity against neutrophil-derived hydroxyl radicals. LVFX markedly improved the survival rate of mice that were infected with the influenza virus in a dose-dependent manner. In addition, the LVFX treatment resulted in a dose-dependent decrease in the level of 8-hydroxy-2'-deoxyguanosine (a marker of oxidative stress and nitrotyrosine (a nitrative marker in the lungs of virus-infected mice, and the nitrite/nitrate ratio (NO metabolites and IFN-γ in BALF. These results indicate that LVFX may be of substantial benefit in the treatment of various acute inflammatory disorders such as influenza virus-induced pneumonia, by inhibiting inflammatory cell responses and suppressing the overproduction of NO in the lungs.

  8. Insights into the Enhanced in vivo Fitness of Neisseria gonorrhoeae Driven by a Fluoroquinolone Resistance-Conferring Mutant DNA Gyrase

    Science.gov (United States)

    2015-02-05

    inoculated into 30 ml of fresh GCB containing 100 µg/ml of streptomycin and supplemented with co-carboxylase, ferric nitrate , and mM NaH2CO3 at the...approximately 8 weeks old, National Cancer Institute, NIH) and cnlp-/- mice in the BALB/c background of a similar age (USUHS breeding colony) were administered

  9. Fluoroquinolone susceptibilities to methicillin-resistant and susceptible coagulase-negative Staphylococcus isolated from eye infection Suscetibilidade dos Staphylococcus coagulase negativo meticilina-resistentes e suscetíveis isolados em infecções oculares

    Directory of Open Access Journals (Sweden)

    Adália Dias Dourado Oliveira

    2007-03-01

    Full Text Available PURPOSE: To evaluate the fluoroquinolone susceptibilities of ocular isolate coagulase-negative staphylococci (CoNS, identified at the Microbiology Laboratory - UNIFESP. DESIGN: Experimental laboratory investigation. METHODS: The minimum inhibitory concentrations (MICs of 21 strains of methicillin-resistant coagulase-negative staphylococci (MRCoNS and 22 methicillin-sensitive coagulase-negative staphylococci (MSCoNS to ciprofloxacin, ofloxacin, gatifloxacin and moxifloxacin were determined, using the E-test method standardized by the Clinical and Laboratory Standards Institute (CLSI/NCCLS. RESULTS: The MIC90s (µg/ml for the second generation of tested fluoroquinolones were higher than the fourth generation, especially for the methicillin-resistant coagulase-negative staphylococci group. CONCLUSION: Our results indicate that methicillin-sensitive coagulase-negative staphylococci are more susceptible to quinolones than are methicillin-resistant coagulase-negative staphylococci and that fourth generation fluoroquinolones appear to be more potent, affecting even coagulase-negative staphylococcal strains resistant to second generation fluoroquinolones.OBJETIVOS: Avaliar a suscetibilidade a fluorquinolonas dos Staphylococcus coagulase-negativo (SCoN identificados no Laboratório de Microbiologia Ocular da Unifesp. MÉTODOS: Foi determinada a concentração inibitória mínima de 21 cepas de SCoN meticilina-resistentes e 22 meticilina-sensíveis para ciprofloxacina, ofloxacina, gatifloxacina e moxifloxacina, utilizando o E-test estandartizado pelo CLSI/NCCLS. RESULTADOS: Os MIC90 (µg/ml de 43 SCoN isolados para fluorquinolonas de segunda geração foram maiores do que os de quarta geração, principalmente para o grupo dos meticilina-resistentes. CONCLUSÃO: Nossos resultados indicam que Staphylococcus coagulase-negativo meticilina-sensíveis são mais suscetíveis às quinolonas do que os Staphylococcus coagulase-negativo meticilina

  10. On Neglecting Chemical Exchange When Correcting in Vivo 31P MRS Data for Partial Saturation: Commentary on: ``Pitfalls in the Measurement of Metabolite Concentrations Using the One-Pulse Experiment in in Vivo NMR''

    Science.gov (United States)

    Ouwerkerk, Ronald; Bottomley, Paul A.

    2001-04-01

    This article replies to Spencer et al. (J. Magn. Reson.149, 251-257, 2001) concerning the degree to which chemical exchange affects partial saturation corrections using saturation factors. Considering the important case of in vivo31P NMR, we employ differential analysis to demonstrate a broad range of experimental conditions over which chemical exchange minimally affects saturation factors, and near-optimum signal-to-noise ratio is preserved. The analysis contradicts Spencer et al.'s broad claim that chemical exchange results in a strong dependence of saturation factors upon M0's and T1 and exchange parameters. For Spencer et al.'s example of a dynamic 31P NMR experiment in which phosphocreatine varies 20-fold, we show that our strategy of measuring saturation factors at the start and end of the study reduces errors in saturation corrections to 2% for the high-energy phosphates.

  11. In vivo proton magnetic resonance spectroscopy (1H-MRS) evaluation of the metabolite concentration of optic radiation in primary open angle glaucoma

    Energy Technology Data Exchange (ETDEWEB)

    Sidek, Sabrilhakim [University of Malaya, Department of Biomedical Imaging, University Malaya Research Imaging Centre (UMRIC), Kuala Lumpur (Malaysia); Universiti Teknologi MARA, Medical Imaging Unit, Faculty of Medicine, Sg Buloh, Selangor (Malaysia); Ramli, Norlisah; Rahmat, Kartini; Kuo, Tan Li [University of Malaya, Department of Biomedical Imaging, University Malaya Research Imaging Centre (UMRIC), Kuala Lumpur (Malaysia); Ramli, Norlina Mohd; Abdulrahman, Fadzlina [University of Malaya, Department of Ophthalmology, Faculty of Medicine, Kuala Lumpur (Malaysia)

    2016-12-15

    To compare the metabolite concentration of optic radiation in glaucoma patients with that of healthy subjects using Proton Magnetic Resonance Spectroscopy (1H-MRS). 1H-MRS utilising the Single-Voxel Spectroscopy (SVS) technique was performed using a 3.0Tesla MRI on 45 optic radiations (15 from healthy subjects, 15 from mild glaucoma patients, and 15 from severe glaucoma patients). A standardised Volume of Interest (VOI) of 20 x 20 x 20 mm was placed in the region of optic radiation. Mild and severe glaucoma patients were categorised based on the Hodapp-Parrish-Anderson (HPA) classification. Mean and multiple group comparisons for metabolite concentration and metabolite concentration ratio between glaucoma grades and healthy subjects were obtained using one-way ANOVA. The metabolite concentration and metabolite concentration ratio between the optic radiations of glaucoma patients and healthy subjects did not demonstrate any significant difference (p > 0.05). Our findings show no significant alteration of metabolite concentration associated with neurodegeneration that could be measured by single-voxel 1H-MRS in optic radiation among glaucoma patients. (orig.)

  12. Increased fluoroquinolone resistance with time in Escherichia coli from >17,000 patients at a large county hospital as a function of culture site, age, sex, and location

    Directory of Open Access Journals (Sweden)

    Hamill Richard J

    2008-01-01

    Full Text Available Abstract Background Escherichia coli infections are common and often treated with fluoroquinolones. Fluoroquinolone resistance is of worldwide importance and is monitored by national and international surveillance networks. In this study, we analyzed the effects of time, culture site, and patient age, sex, and location on fluoroquinolone resistance in E. coli clinical isolates. Methods To understand how patient factors and time influenced fluoroquinolone resistance and to determine how well data from surveillance networks predict trends at Ben Taub General Hospital in Houston, TX, we used Perl to parse and MySQL to house data from antibiograms (n ≅ 21,000 for E. coli isolated between 1999 to 2004 using Chi Square, Bonferroni, and Multiple Linear Regression methods. Results Fluoroquinolone resistance (i increased with time; (ii exceeded national averages by 2- to 4-fold; (iii was higher in males than females, largely because of urinary isolates from male outpatients; (iv increased with patient age; (v was 3% in pediatric patients; (vi was higher in hospitalized patients than outpatients; (vii was higher in sputum samples, particularly from inpatients, than all other culture sites, including blood and urine, regardless of patient location; and (viii was lowest in genital isolates than all other culture sites. Additionally, the data suggest that, with regard to susceptibility or resistance by the Dade Behring MicroScan system, a single fluoroquinolone suffices as a "surrogate marker" for all of the fluoroquinolone tested. Conclusion Large surveillance programs often did not predict E. coli fluoroquinolone resistance trends at a large, urban hospital with a largely indigent, ethnically diverse patient population or its affiliated community clinics.

  13. Magnetic nanoparticles modified with polydimethylsiloxane and multi-walled carbon nanotubes for solid-phase extraction of fluoroquinolones

    International Nuclear Information System (INIS)

    Xu, S.; Jiang, C.; Lin, Y.; Jia, L.

    2012-01-01

    We have surface-functionalized magnetic particles (MPs) with polydimethylsiloxane and multi-walled carbon nanotubes in a two-step reaction. The MPs were applied to solid-phase extraction of the fluoroquinolones ofloxacin, norfloxacin, ciprofloxacin, enrofloxacin prior to their determination by capillary liquid chromatography. The effects of sample pH, adsorption time, type of eluent, desorption time and desorption temperature were investigated. Under the optimum conditions, the extraction efficiencies are in the range from 81.5 % to 94.1 %, with relative standard deviations (RSDs) of -1 . The method was applied to the analysis of spiked mineral water and honey. The recoveries for the fluoroquinolones in the real samples range from 84.0 % to 112 %, with RSDs ranging from 2.9 % to 7.8 %. (author)

  14. In vivo 3D measurement of moxifloxacin and gatifloxacin distributions in the mouse cornea using multiphoton microscopy

    OpenAIRE

    Lee, Seunghun; Lee, Jun Ho; Park, Jin Hyoung; Yoon, Yeoreum; Chung, Wan Kyun; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean

    2016-01-01

    Moxifloxacin and gatifloxacin are fourth-generation fluoroquinolone antibiotics used in the clinic to prevent or treat ocular infections. Their pharmacokinetics in the cornea is usually measured from extracted ocular fluids or tissues, and in vivo direct measurement is difficult. In this study multiphoton microscopy (MPM), which is a 3D optical microscopic technique based on multiphoton fluorescence, was applied to the measurement of moxifloxacin and gatifloxacin distribution in the cornea. I...

  15. Emergence of fluoroquinolone resistance among drug resistant tuberculosis patients at a tertiary care facility in Karachi, Pakistan.

    Science.gov (United States)

    Zaidi, Syed Mohammad Asad; Haseeb, Abdul; Habib, Shifa Salman; Malik, Amyn; Khowaja, Saira; SaifUllah, Nausheen; Rizvi, Nadeem

    2017-07-25

    Pakistan is classified as one of the high multi-drug resistant tuberculosis (MDR-TB) burden countries. A poorly regulated private sector, over-prescription of antibiotics and self-medication has led to augmented rates of drug-resistance in the country. Pakistan's first national anti-tuberculosis drug resistance survey identified high prevalence of fluoroquinolone resistance among MDR-TB patients. Further institutional evidence of fluoroquinolone drug-resistance can support re-evaluation of treatment regimens as well as invigorate efforts to control antibiotic resistance in the country. In this study, data for drug-susceptibility testing (DST) was retrospectively analyzed for a total of 133 patients receiving MDR-TB treatment at the Chest Department of Jinnah Postgraduate Medical Center, Karachi, Pakistan. Frequency analyses for resistance patterns was carried out and association of fluoroquinolone (ofloxacin) resistance with demographics and past TB treatment category were assessed. Within first-line drugs, resistance to isoniazid was detected in 97.7% of cases, followed by rifampicin (96.9%), pyrazinamide (86.4%), ethambutol (69.2%) and streptomycin (64.6%). Within second-line drugs, ofloxacin resistance was detected in 34.6% of cases. Resistance to ethionamide and amikacin was 2.3% and 1.6%, respectively. Combined resistance of oflaxacin and isoniazid was detected in 33.9% of cases. Age, gender and past TB treatment category were not significantly associated with resistance to ofloxacin. Fluoroquinolone resistance was observed in an alarmingly high proportion of MDR-TB cases. Our results suggest caution in their use for empirical management of MDR-TB cases and recommended treatment regimens for MDR-TB may require re-evaluation. Greater engagement of private providers and stringent pharmacy regulations are urgently required.

  16. [Susceptibility surveillance of clinical isolates to fluoroquinolone antimicrobial agents from 2003 to 2008: post-marketing study of prulifloxacin].

    Science.gov (United States)

    Kawai, Shin; Yoshida, Atsushi; Okazaki, Mitsuhiro; Tsujihara, Yoshito; Inuzuka, Kazuhisa; Takeuchi, Kazuhide; Yamashita, Naoko; Onodera, Makoto; Hiraishi, Toru; Ida, Takashi; Maebashi, Kazunori

    2010-06-01

    Yearly changes in the susceptibility of clinical isolates to ulifloxacin (UFX) and other fluoroquinolones were examined through surveys over 3 periods. In the first survey, 534 strains derived from 19 species were collected from clinical specimens during 6 months from December 2003 to May 2004. In the same way, 805 strains were collected from December 2005 to May 2006 in the second survey, and 863 strains were from December 2007 to May 2008 in the third survey. Over these 3 study periods, the susceptibilities of fluoroquinolones against methicillin-susceptible Staphylococcus aureus and Escherichia coli were decreased. The isolation frequency of levofloxacin-nonsusceptible strain was increased from 0% to 11.8% and from 14.6% to 20.8%, respectively. MIC90s of UFX against these pathogens were also increased, but its MIC90 for E. coli was 2 to 4 times lower than that of levofloxacin. On the other hand, the susceptibility of strains of Klebsiella pneumoniae to UFX was increased. Among the fluoroquinolones tested, UFX showed the most potent activity against Pseudomonas aeruginosa, and no changes in the MIC90s occurred during the surveillance. Although one strain of Streptococcus pneumoniae isolated in the third study period showed levofloxacin-resistance (MIC, 8 microg/mL), there were nearly no changes in the MIC90s of any agents tested including UFX against S. pneumoniae during the surveillance. As for other bacterial species, a tendency to increase in resistance to UFX was not observed. The activity of UFX against Salmonella spp. and Shigella spp. was superior/equal to those of fluoroquinolones tested.

  17. In vivo magnetic resonance spectroscopy measurement of gray-matter and white-matter gamma-aminobutyric acid concentration in sensorimotor cortex using a motion-controlled MEGA point-resolved spectroscopy sequence.

    Science.gov (United States)

    Bhattacharyya, Pallab K; Phillips, Micheal D; Stone, Lael A; Lowe, Mark J

    2011-04-01

    Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Understanding the GABA concentration, in vivo, is important to understand normal brain function. Using MEGA point-resolved spectroscopy sequence with interleaved water scans to detect subject motion, GABA level of sensorimotor cortex was measured using a voxel identified from a functional magnetic resonance imaging scan. The GABA level in a 20×20×20-mm(3) voxel consisting of 37%±7% gray matter, 52%±12% white matter and 11%±8% cerebrospinal fluid in the sensorimotor region was measured to be 1.43±0.48 mM. In addition, using linear regression analysis, GABA concentrations within gray and white matter were calculated to be 2.87±0.61 and 0.33±0.11 mM, respectively. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Abnormal Concentration of GABA and Glutamate in The Prefrontal Cortex in Schizophrenia.-An in Vivo 1H-MRS Study.

    Science.gov (United States)

    Chen, Tianyi; Wang, Yingchan; Zhang, Jianye; Wang, Zuowei; Xu, Jiale; Li, Yao; Yang, Zhilei; Liu, Dengtang

    2017-10-25

    The etiology and pathomechanism of schizophrenia are unknown. The traditional dopamine (DA) hypothesis is unable to fully explain its pathology and therapeutics. The glutamate (Glu) and γ-aminobutyric acid (GABA) hypotheses suggest Glu or GABA concentrations are abnormal in the brains of patients with schizophrenia. Magnetic resonance spectroscopy (MRS) show glutamate level increases in the ventromedial prefrontal cortex (vmPFC) including the anterior cingulated cortex (ACC) in those with schizophrenia. To investigate the function of the glutamate system (glutamate and γ-aminobutyric acid) in the etiology and pathomechanism of schizophrenia. 24 drug naïve patients with schizophrenia and 24 healthy volunteers were matched by gender, age, and educational level. The Siemens 3T MRI system was used to collect the magnetic resonance spectroscopy (MRS) data of the subjects. The regions of interest included the left dorsolateral prefrontal cortex (IDLPFC), ventromedial prefrontal cortex (vmPFC), and anterior cingulate cortex (ACC). LCModel software was used to analyze the concentrations of γ-aminobutyric acid (GABA), glutamate (Glu), glutamine (Gln), N-acetylaspartate (NAA), and N-acetylaspartylglutamate (NAAG) in the region of interest. Meanwhile, the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Scale (CGI) were used to assess the mental symptoms and severity of the disease. The median GABA concentrations in the anterior cingulate cortex of the schizophrenia group and the healthy control group were 1.90 (Q1=1.55, Q3=2.09) and 2.16 (Q1=1.87, Q3=2.59) respectively; the mean (sd) Glu concentrations were 6.07 (2.48) and 6.54 (1.99); the median Gln concentrations were 0.36 (Q1=0.00, Q3=0.74) and 0.29 (Q1=0.00, Q3=0.59); the between-group difference of the GABA concentrations was statistically significant ( Z =-2.95, p =0.003); the between-group difference of the GABA/(NAA+NAAG) was statistically significant ( Z =-2.72, p =0.012); the

  19. In vivo and in vitro changes in neurochemical parameters related to mercury concentrations from specific brain regions of polar bears (Ursus maritimus).

    Science.gov (United States)

    Krey, Anke; Kwan, Michael; Chan, Hing Man

    2014-11-01

    Mercury (Hg) has been detected in polar bear brain tissue, but its biological effects are not well known. Relationships between Hg concentrations and neurochemical enzyme activities and receptor binding were assessed in the cerebellum, frontal lobes, and occipital lobes of 24 polar bears collected from Nunavik (Northern Quebec), Canada. The concentration-response relationship was further studied with in vitro experiments using pooled brain homogenate of 12 randomly chosen bears. In environmentally exposed brain samples, there was no correlative relationship between Hg concentration and cholinesterase (ChE) activity or muscarinic acetylcholine receptor (mAChR) binding in any of the 3 brain regions. Monoamine oxidase (MAO) activity in the occipital lobe showed a negative correlative relationship with total Hg concentration. In vitro experiments, however, demonstrated that Hg (mercuric chloride and methylmercury chloride) can inhibit ChE and MAO activities and muscarinic mAChR binding. These results show that Hg can alter neurobiochemical parameters but the current environmental Hg exposure level does have an effect on the neurochemistry of polar bears from northern Canada. © 2014 SETAC.

  20. Tolerance of Escherichia coli to fluoroquinolone antibiotics depends on specific components of the SOS response pathway.

    Science.gov (United States)

    Theodore, Alyssa; Lewis, Kim; Vulic, Marin

    2013-12-01

    Bacteria exposed to bactericidal fluoroquinolone (FQ) antibiotics can survive without becoming genetically resistant. Survival of these phenotypically resistant cells, commonly called "persisters," depends on the SOS gene network. We have examined mutants in all known SOS-regulated genes to identify functions essential for tolerance in Escherichia coli. The absence of DinG and UvrD helicases and the Holliday junction processing enzymes RuvA and RuvB leads to a decrease in survival. Analysis of the respective mutants indicates that, in addition to repair of double-strand breaks, tolerance depends on the repair of collapsed replication forks and stalled transcription complexes. Mutation in recF results in increased survival, which identifies RecAF recombination as a poisoning mechanism not previously linked to FQ lethality. DinG acts upstream of SOS promoting its induction, whereas RuvAB participates in repair only. UvrD directly promotes all repair processes initiated by FQ-induced damage and prevents RecAF-dependent misrepair, making it one of the crucial SOS functions required for tolerance.

  1. Azithromycin, fluoroquinolone and chloramphenicol resistance of non-chlamydia conjunctival bacteria in rural community of Ethiopia

    Directory of Open Access Journals (Sweden)

    Bayeh Abera

    2014-01-01

    Full Text Available Aim: To determine profiles of non-chlamydia conjunctival bacteria and their antimicrobial susceptibility from adults who underwent trachomatous trichiasis surgery in rural areas of Ethiopia. Materials and Methods: A cross-sectional study was conducted in rural districts in West Gojjam administrative zone. Conjunctival swabs were collected during surgery and transported using Stuart transport broth (Oxoid, UK. Antibiotic susceptibility of conjunctival isolates was determined using the Kirby-Bauer disc-diffusion method. Results: Non-chlamydia pathogenic bacteria were recovered from conjunctiva of 438 (31% participants before treatment. The isolated conjunctival bacteria were Staphylococcus aureus, coagulase-negative Staphylococci, Streptococcus group (A, C, F and G, Enterococci, Streptococcus pneumoniae, Moraxella spp., Escherichia coli, Citrobacter spp., Proteus spp., Klebsiella spp., Pseudomonas spp. and Enterobacter spp. Overall, resistance rates of 57.8% to azithromycin and 68.5% to chloramphenicol were found. However, 86-94.4% sensitivity was demonstrated to ciprofloxacin and norfloxacin. Moderate sensitivity rates (61.8-78.4% were observed to ceftriaxone, tetracycline and cotrimoxazole. Conclusion: Fluoroquinolones that have activity against the majority of bacterial isolates were potent at in vitro. However, unacceptably high levels of resistance to azithromycin and chloramphenicol in rural community indicated a need for further study and antimicrobial resistance surveillance.

  2. CLINICAL USE OF MODERN FLUOROQUINOLONES IN DENTAL IMPLANTATION AND MAXILLARY SINUS LIFTING

    Directory of Open Access Journals (Sweden)

    S.A. Novikov

    2009-03-01

    Full Text Available New fluoroquinolones like levofloxacine, with broad-spectrum of effect which is also active against anaerobic bacteria, is a prospective drug for the prevention of the inflammatory complications in implant dentistry and maxillary sinus augmentation. 34 patients have been selected for this study, including 16 women and 18 men aged 18-65. All the patients have been classified into the main and control groups. Patiens of the first group have been prescribed 500 mg of levofloxacine before and after the operation two times a day for 10 days. Patients of the control group have been treated with amocxicilline. In the control group, which has used amoxicilline, Streptococcus sanguis, Streptococcus salivarius and anaerobic bacteria have been identified. The amount of Prevotella intermedia is insignificant. The same picture has been found with Fusobacterium spp. The rate of Actinomyces spp. was insignificant over the whole period of study. Patients of the experimental group had a slightly different distribution of bacteria. On the 10th day after the operation in the main patient group no periodontal pathogenesis, which may cause inflammatory complications have been identified. During the early post-operative period no significant differences have been observed among the patients of both groups.

  3. Efficacy of prophylactic single-dose therapy using fluoroquinolone for prostate brachytherapy

    International Nuclear Information System (INIS)

    Nomura, Takeo; Hirai, Kenichi; Yamasaki, Mutsushi; Inoue, Toru; Takahashi, Mika; Kawashima, Takayuki; Sato, Fuminori; Mimata, Hiromitsu

    2012-01-01

    There is little definitive evidence to guide the use of prophylactic antibiotics for prostate brachytherapy. The purpose of this study is to evaluate the incidence of postimplant infections in patients who receive antimicrobial prophylaxis with pazufloxacin (PZFX). A total of 84 patients who underwent prostate brachytherapy received a single intravenous dose of PZFX at 500 mg perioperatively for 1 day. No postimplant antibiotic medication was prescribed. Urinalysis, plasma white blood cell (WBC) count, and C reactive protein (CRP) levels were evaluated before the implantation, on the day after implantation, and on the 7th and 28th days after brachytherapy. None of the 84 patients (0.0%) developed a symptomatic urinary tract infection or had febrile infectious complications after brachytherapy. There were statistically significant elevations in the levels of erythrocytes, leukocytes, bacteria in urine, plasma WBC and CRP postoperatively, but these values did not exceed the normal range or were only slightly elevated on the day after brachytherapy (day 1) and on day 7. All laboratory examinations had returned to the normal range on day 28. Single-dose therapy with fluoroquinolone helps to prevent infections after prostate brachytherapy. (author)

  4. Adsorptive Removal and Adsorption Kinetics of Fluoroquinolone by Nano-Hydroxyapatite.

    Directory of Open Access Journals (Sweden)

    Yajun Chen

    Full Text Available Various kinds of antibiotics, especially fluoroquinolone antibiotics (FQs have been widely used for the therapy of infectious diseases in human and livestock. For their poorly absorbed by living organisms, large-scale misuse or abuse of FQs will foster drug resistance among pathogenic bacteria, as well as a variety of environmental problems when they were released in the environment. In this work, the adsorption properties of two FQs, namely norfloxacin (NOR and ciprofloxacin (CIP, by nano-hydroxyapatite (n-HAP were studied by batch adsorption experiments. The adsorption curves of FQs by n-HAP were simulated by Langmuir and Freundlich isotherms. The results shown that NOR and CIP can be adsorbed effectively by the adsorbent of n-HAP, and the adsorption capacity of FQs increase with increasing dosage of n-HAP. The optimum dosage of n-HAP for FQs removal was 20 g · L(-1, in which the removal efficiencies is 51.6% and 47.3%, and an adsorption equilibrium time is 20 min. The maximum removal efficiency occurred when pH is 6 for both FQs. The adsorption isotherm of FQs fits well for both Langmuir and Freundlich equations. The adsorption of both FQs by n-HAP follows second-order kinetics.

  5. Adsorptive Removal and Adsorption Kinetics of Fluoroquinolone by Nano-Hydroxyapatite

    Science.gov (United States)

    Chen, Yajun; Lan, Tao; Duan, Lunchao; Wang, Fenghe; Zhao, Bin; Zhang, Shengtian; Wei, Wei

    2015-01-01

    Various kinds of antibiotics, especially fluoroquinolone antibiotics (FQs) have been widely used for the therapy of infectious diseases in human and livestock. For their poorly absorbed by living organisms, large-scale misuse or abuse of FQs will foster drug resistance among pathogenic bacteria, as well as a variety of environmental problems when they were released in the environment. In this work, the adsorption properties of two FQs, namely norfloxacin (NOR) and ciprofloxacin (CIP), by nano-hydroxyapatite (n-HAP) were studied by batch adsorption experiments. The adsorption curves of FQs by n-HAP were simulated by Langmuir and Freundlich isotherms. The results shown that NOR and CIP can be adsorbed effectively by the adsorbent of n-HAP, and the adsorption capacity of FQs increase with increasing dosage of n-HAP. The optimum dosage of n-HAP for FQs removal was 20 g·L-1, in which the removal efficiencies is 51.6% and 47.3%, and an adsorption equilibrium time is 20 min. The maximum removal efficiency occurred when pH is 6 for both FQs. The adsorption isotherm of FQs fits well for both Langmuir and Freundlich equations. The adsorption of both FQs by n-HAP follows second-order kinetics. PMID:26698573

  6. Low serum cartonectin/CTRP3 concentrations in newly diagnosed type 2 diabetes mellitus: in vivo regulation of cartonectin by glucose.

    Directory of Open Access Journals (Sweden)

    Bo Ban

    Full Text Available OBJECTIVES: Cartonectin is a novel adipokine of the C1q complement/TNF-related protein (CTRP superfamily, with glucose lowering effects, anti-inflammatory and cardio-protective properties. We sought to investigate circulating cartonectin concentrations in subjects with type 2 diabetes mellitus (T2DM as well as age and BMI matched control subjects. We also examined the effects of a 2 hour 75 g oral glucose tolerance test (OGTT on serum cartonectin concentrations in T2DM subjects. DESIGN: Cross-sectional study [newly diagnosed (first discovery, not on any treatments T2DM (n = 47 and control (n = 63 subjects]. Serum cartonectin was measured by ELISA. RESULTS: Serum cartonectin concentrations were significantly lower in patients with T2DM compared to controls (P0.05. There were no significant correlations in T2DM subjects (n = 47. In control subjects (n = 63, serum cartonectin was significantly negatively correlated with CRP, and significantly positively correlated with insulin, HOMA-IR and leptin. However, when subjected to multiple regression analysis, none of these variables were predictive of serum cartonectin (P>0.05. Finally, serum cartonectin concentrations were significantly lower in T2DM subjects after a 2 hour 75 g OGTT (P<0.01. CONCLUSIONS: Cartonectin may serve as a novel biomarker for the prediction and early diagnosis of T2DM patients. Furthermore, cartonectin and/or pharmacological agents that increase circulating cartonectin levels can represent a new therapeutic field in the treatment of T2DM patients. Further research is needed to clarify these points.

  7. Identification and Characterization of Fluoroquinolone Non-susceptible Streptococcus pyogenes Clones Harboring Tetracycline and Macrolide Resistance in Shanghai, China

    Directory of Open Access Journals (Sweden)

    Yinfang Shen

    2018-03-01

    Full Text Available Streptococcus pyogenes, also known as group A Streptococcus (GAS, is one of the top 10 infectious causes of death worldwide. Macrolide and tetracycline resistant GAS has emerged as a major health concern in China coinciding with an ongoing scarlet fever epidemic. Furthermore, increasing rates of fluoroquinolone (FQ non-susceptibility within GAS from geographical regions outside of China has also been reported. Fluoroquinolones are the third most commonly prescribed antibiotic in China and is an therapeutic alternative for multi-drug resistant GAS. The purpose of this study was to investigate the epidemiological and molecular features of GAS fluoroquinolone (FQ non-susceptibility in Shanghai, China. GAS (n = 2,258 recovered between 2011 and 2016 from children and adults were tested for FQ-non-susceptibility. Efflux phenotype and mutations in parC, parE, gyrA, and gyrB were investigated and genetic relationships were determined by emm typing, pulsed-field gel electrophoresis and phylogenetic analysis. The frequency of GAS FQ-non-susceptibility was 1.3% (30/2,258, with the phenotype more prevalent in GAS isolated from adults (14.3% than from children (1.2%. Eighty percent (24/30 of FQ-non-susceptible isolates were also resistant to both macrolides (ermB and tetracycline (tetM including the GAS sequence types emm12, emm6, emm11, and emm1. Genomic fingerprinting analysis of the 30 isolates revealed that non-susceptibility may arise in various genetic backgrounds even within a single emm type. No efflux phenotype was observed in FQ non-susceptible isolates, and molecular analysis of the quinolone resistance-determining regions (QRDRs identified several sequence polymorphisms in ParC and ParE, and none in GyrA and GyrB. Expansion of this analysis to 152 publically available GAS whole genome sequences from Hong Kong predicted 7.9% (12/152 of Hong Kong isolates harbored a S79F ParC mutation, of which 66.7% (8/12 were macrolide and tetracycline resistant

  8. In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET - influence of menstrual cycle and endogenous estrogen level

    International Nuclear Information System (INIS)

    Tsuchida, Tatsuro; Okazawa, Hidehiko; Mori, Tetsuya; Kobayashi, Masato; Yoshida, Yoshio; Fujibayashi, Yasuhisa; Itoh, Harumi

    2007-01-01

    Purpose: The goals of this study were to measure estrogen receptor (ER) concentration in the endometrium and myometrium using 16α-[ 18 F]fluoro-17β-estradiol (FES) positron emission tomography (PET) and to investigate the relationship between changes in these parameters with the menstrual cycle and endogenous estrogen levels. Methods: Sixteen female healthy volunteers were included in this study. After blood sampling to measure endogenous estrogen level, FES PET image was acquired 60 min postinjection of FES. After whole-body imaging of FES PET, averaged standardized uptake values (SUVs) in the endometrium and myometrium were measured, and the relationship between FES uptake and menstrual cycle or endogenous estrogen level was evaluated. Results: Endometrial SUV was significantly higher in the proliferative phase than in the secretory phase (6.03±1.05 vs. 3.97±1.29, P=.022). In contrast, there was no significant difference in myometrial SUV when the proliferative and secretory phases were compared (P=.23). Further, there was no correlation between SUV and endogenous estrogen level in the proliferative phase. Conclusions: The change of ER concentration relative to menstrual cycle as characterized by FES PET was consistent with those from previous reports that used an immunohistochemical technique. These data suggest that FES PET is a feasible, noninvasive method for characterizing changes in ER concentration

  9. In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET - influence of menstrual cycle and endogenous estrogen level

    Energy Technology Data Exchange (ETDEWEB)

    Tsuchida, Tatsuro [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)]. E-mail: tsucchy@fmsrsa.fukui-med.ac.jp; Okazawa, Hidehiko [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Mori, Tetsuya [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Kobayashi, Masato [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Yoshida, Yoshio [Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Fujibayashi, Yasuhisa [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan); Itoh, Harumi [Department of Radiology, Faculty of Medical Sciences, University of Fukui, Yoshida-gun, Fukui 910-1193 (Japan)

    2007-02-15

    Purpose: The goals of this study were to measure estrogen receptor (ER) concentration in the endometrium and myometrium using 16{alpha}-[{sup 18}F]fluoro-17{beta}-estradiol (FES) positron emission tomography (PET) and to investigate the relationship between changes in these parameters with the menstrual cycle and endogenous estrogen levels. Methods: Sixteen female healthy volunteers were included in this study. After blood sampling to measure endogenous estrogen level, FES PET image was acquired 60 min postinjection of FES. After whole-body imaging of FES PET, averaged standardized uptake values (SUVs) in the endometrium and myometrium were measured, and the relationship between FES uptake and menstrual cycle or endogenous estrogen level was evaluated. Results: Endometrial SUV was significantly higher in the proliferative phase than in the secretory phase (6.03{+-}1.05 vs. 3.97{+-}1.29, P=.022). In contrast, there was no significant difference in myometrial SUV when the proliferative and secretory phases were compared (P=.23). Further, there was no correlation between SUV and endogenous estrogen level in the proliferative phase. Conclusions: The change of ER concentration relative to menstrual cycle as characterized by FES PET was consistent with those from previous reports that used an immunohistochemical technique. These data suggest that FES PET is a feasible, noninvasive method for characterizing changes in ER concentration.

  10. Non-invasive in vivo determination of the carotenoids beta-carotene and lycopene concentrations in the human skin using the Raman spectroscopic method

    Energy Technology Data Exchange (ETDEWEB)

    Darvin, M E [Center of Experimental and Applied Cutaneous Physiology (CCP), Department of Dermatology, Charite University Hospital, Berlin (Germany); Gersonde, I [Institute of Medical Physics and Laser Medicine, Charite University Hospital, Berlin (Germany); Meinke, M [Institute of Medical Physics and Laser Medicine, Charite University Hospital, Berlin (Germany); Sterry, W [Center of Experimental and Applied Cutaneous Physiology (CCP), Department of Dermatology, Charite University Hospital, Berlin (Germany); Lademann, J [Center of Experimental and Applied Cutaneous Physiology (CCP), Department of Dermatology, Charite University Hospital, Berlin (Germany)

    2005-08-07

    Resonance Raman spectroscopy was used as a fast and non-invasive optical method of measuring the absolute concentrations of beta-carotene and lycopene in living human skin. Beta-carotene and lycopene have different absorption values at 488 and 514.5 nm and, consequently, the Raman lines for beta-carotene and lycopene have different scattering efficiencies at 488 and 514.5 nm excitations. These differences were used for the determination of the concentrations of beta-carotene and lycopene. Using multiline Ar{sup +} laser excitation, clearly distinguishable carotenoid Raman spectra can be obtained which are superimposed on a large fluorescence background. The Raman signals are characterized by two prominent Stokes lines at 1160 and 1525 cm{sup -1}, which have nearly identical relative intensities. Both substances were detected simultaneously. The Raman spectra are obtained rapidly, i.e. within about 10 s, and the required laser light exposure level is well within safety standards. The disturbance of the measurements by non-homogeneous skin pigmentation was avoided by using a relatively large measuring area of 35 mm{sup 2}. It was shown that beta-carotene and lycopene distribution in human skin strongly depends upon the skin region studied and drastically changed inter-individually. Skin beta-carotene and lycopene concentrations are lower in smokers than in non-smokers and higher in the vegetarian group.

  11. Case study: in vivo stress diagnostics by spectroscopic determination of the cutaneous carotenoid antioxidant concentration in midwives depending on shift work

    International Nuclear Information System (INIS)

    Maeter, H; Briese, V; Gerber, B; Darvin, M E; Lademann, J; Olbertz, D M

    2013-01-01

    Laser spectroscopic methods, for instance resonance Raman spectroscopy and reflectance spectroscopy, permit us for the first time to investigate the antioxidative status in human skin non-invasively by measurement of carotenoid concentration. The individual antioxidant concentration of the human skin is determined by the nutritional habits, on the one hand, and by stressors, such as shift work, on the other. Due to the disturbance of the circadian rhythm and melatonin secretion, shift work is associated with, inter alia, insomnia and gastrointestinal disorders. The study at hand was the first to determine the cutaneous antioxidant concentration of midwives using reflectance spectroscopy and to relate the results to shift work. Seven midwives took part in the study. An LED-based compact scanner system was used for non-invasive measurements of carotenoids in human skin. The measuring principle is based on reflection spectroscopy. The study at hand suggests that the cutaneous antioxidative status may be adversely affected by shift work. Despite numerous international strategies of programmes available which invite people to eat more healthily, there are only a few measures aiming at stress reduction and management. In this field the use of reflectance spectroscopic investigation methods could play an essential role in the future. (letter)

  12. Non-invasive in vivo determination of the carotenoids beta-carotene and lycopene concentrations in the human skin using the Raman spectroscopic method

    International Nuclear Information System (INIS)

    Darvin, M E; Gersonde, I; Meinke, M; Sterry, W; Lademann, J

    2005-01-01

    Resonance Raman spectroscopy was used as a fast and non-invasive optical method of measuring the absolute concentrations of beta-carotene and lycopene in living human skin. Beta-carotene and lycopene have different absorption values at 488 and 514.5 nm and, consequently, the Raman lines for beta-carotene and lycopene have different scattering efficiencies at 488 and 514.5 nm excitations. These differences were used for the determination of the concentrations of beta-carotene and lycopene. Using multiline Ar + laser excitation, clearly distinguishable carotenoid Raman spectra can be obtained which are superimposed on a large fluorescence background. The Raman signals are characterized by two prominent Stokes lines at 1160 and 1525 cm -1 , which have nearly identical relative intensities. Both substances were detected simultaneously. The Raman spectra are obtained rapidly, i.e. within about 10 s, and the required laser light exposure level is well within safety standards. The disturbance of the measurements by non-homogeneous skin pigmentation was avoided by using a relatively large measuring area of 35 mm 2 . It was shown that beta-carotene and lycopene distribution in human skin strongly depends upon the skin region studied and drastically changed inter-individually. Skin beta-carotene and lycopene concentrations are lower in smokers than in non-smokers and higher in the vegetarian group

  13. Determination of fluoroquinolone antibiotics by microchip capillary electrophoresis along with time-resolved sensitized luminescence of their terbium(III) complexes

    International Nuclear Information System (INIS)

    Sierra-Rodero, Marina; Fernández -Romero, Juan Manuel; Gómez -Hens, Agustina

    2014-01-01

    We report on the time-resolved detection of the three fluoroquinolone (FQs) antibiotics ciprofloxacin (CIP), enrofloxacin (ENR) and flumequine (FLU). On addition of terbium(III) ions, the terbium(III)-FQs chelates are formed in-situ in an on-capillary derivatization reaction of a microfluidic system. The laser-induced terbium(III)-sensitized luminescence of the chelates is measured at excitation/emission wavelengths of 337/545 nm. The analytes can be separated and quantified within less than 4 min. A solid phase extraction step for analyte preconcentration can be included prior to chelation and microchip capillary electrophoresis. The analytical ranges of the calibration graphs for CIP, ENR and FLU are from 10.6 to 60.0, 10.3 to 51.0, and 11.5 to 58.8 ng mL −1 , respectively, and the detection limits are 3.2, 3.1 and 3.6 ng mL −1 , respectively. The precision was established at two concentration levels of each analyte and revealed relative standard deviations in the range from 3.0 to 10.2 %. The method was applied to the analysis of FQ-spiked water samples. (author)

  14. Sustained release of bactericidal concentrations of penicillin in the pleural space via an antibiotic-eluting pigtail catheter coated with electrospun nanofibers: results from in vivo and in vitro studies.

    Science.gov (United States)

    Chao, Yin-Kai; Lee, Cheng-Hung; Liu, Kuo-Sheng; Wang, Yi-Chuan; Wang, Chih-Wei; Liu, Shih-Jung

    2015-01-01

    Inadequate intrapleural drug concentrations caused by poor penetration of systemic antibiotics into the pleural cavity is a major cause of treatment failure in empyema. Herein, we describe a novel antibiotic-eluting pigtail catheter coated with electrospun nanofibers used for the sustained release of bactericidal concentrations of penicillin in the pleural space. Electrospun nanofibers prepared using polylactide-polyglycolide copolymer and penicillin G sodium dissolved in 1,1,1,3,3,3-hexafluoro-2-propanol were used to coat the surface of an Fr6 pigtail catheter. The in vitro patterns of drug release were tested by placing the catheter in phosphate-buffered saline. In vivo studies were performed using rabbits treated with penicillin either intrapleurally (Group 1, 20 mg delivered through the catheter) or systemically (Group 2, intramuscular injection, 10 mg/kg). Penicillin concentrations in the serum and pleural fluid were then measured and compared. In vitro studies revealed a burst release of penicillin (10% of the total dose) occurring in the first 24 hours, followed by a sustained release in the subsequent 30 days. Intrapleural drug levels were significantly higher in Group 1 than in Group 2 (Ppenicillin concentrations remained above the minimum inhibitory concentration breakpoint throughout the entire study period. In contrast, serum penicillin levels were significantly higher in Group 2 than in Group 1 (P<0.001). Notably, all Group 2 rabbits showed signs of systemic toxicity (paralytic ileus and weight loss). We conclude that our antibiotic-eluting catheter may serve as a novel therapeutic option to treat empyema.

  15. Molecular epidemiology of fluoroquinolone resistant Salmonella in Africa: A systematic review and meta-analysis.

    Science.gov (United States)

    Tadesse, Getachew; Tessema, Tesfaye S; Beyene, Getenet; Aseffa, Abraham

    2018-01-01

    Wide-ranging evidence on the occurrence of fluoroquinolone (FQ) resistance genetic determinants in African Salmonella strains is not available. The main objectives of this study were to assess the heterogeneity, estimate pooled proportions and describe the preponderance of FQ-resistance determinants in typhoidal and non-typhoidal Salmonella (NTS) isolates of Africa. Genetic and phenotypic data on 6103 Salmonella isolates were considered. Meta- and frequency analyses were performed depending on the number of studies by category, number of isolates and risks of bias. A random effects model was used to assess heterogeneity and estimate pooled proportions. Relative and cumulative frequencies were calculated to describe the overall preponderance of FQ-resistance determinants in quinolone resistant isolates. The pooled proportion of gyrA mutants (Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Salmonella enterica serovar Enteritidis) was estimated at 5.7% (95% Confidence interval (CI) = 2.6, 9.8; Tau squared (T2) = 0.1105), and was higher in S. Typhi than in S. Typhimurium (odds ratio (OR) = 3.3, 95%CI = 2, 5.7). The proportions of each of gyrB and parC mutants, and strains with Plasmid Mediated Quinolone Resistance genes (qnrA, qnrB and qnrS) were low (≤ 0.3%). Overall, 23 mutant serotypes were identified, and most strains had mutations at codons encoding Ser83 and Asp87 of gyrA (82%, 95%CI = 78, 86). Mutations at gyrA appear to account for ciprofloxacin non-susceptibility in most clinical Salmonella strains in Africa. The estimates could be harnessed to develop a mismatch-amplification mutation-assay for the detection of FQ-resistant strains in Africa.

  16. Structures and mechanisms in clay nanopore trapping of structurally-different fluoroquinolone antimicrobials.

    Science.gov (United States)

    Okaikue-Woodi, Fanny E K; Kelch, Sabrina E; Schmidt, Michael P; Enid Martinez, Carmen; Youngman, Randall E; Aristilde, Ludmilla

    2018-03-01

    Smectite clay nanoparticles are implicated in the retention of antimicrobials within soils and sediments; these clays are also inspected as drug carriers in physiological systems. Cation exchange is considered the primary adsorption mechanism of antimicrobials within smectite nanopores. However, a dual role of acid-base chemistry and adsorptive structures is speculated by recent studies. Using the prototypical smectite clay montmorillonite, we employed a combination of X-ray diffraction (XRD), nuclear magnetic resonance, attenuated total reflectance-Fourier transform infrared spectroscopy, and molecular dynamics simulations to investigate the interlayer nanopore trapping of two structurally-different fluoroquinolone (FQ) antimicrobials with similar acid-base chemistry: ciprofloxacin (a first-generation FQ) and moxifloxacin (a third-generation FQ). Greater sorption at pH 5.0 than at pH 7.0 for both FQs was consistent with cation-exchange of positively-charged species. However, the clay exhibited a near twofold higher sorption capacity for moxifloxacin than for ciprofloxacin. This difference was shown by the XRD data to be accompanied by enhanced trapping of moxifloxacin within the clay interlayers. Using the XRD-determined nanopore sizes, we performed molecular dynamics simulations of thermodynamically-favorable model adsorbates, which revealed that ciprofloxacin was adsorbed parallel to the clay surface but moxifloxacin adopted a tilted conformation across the nanopore. These conformations resulted in more slowly-exchanged than quickly-exchanged Na complexes with ciprofloxacin compared with moxifloxacin. These different Na populations were also captured by 23 Na nuclear magnetic resonance. Furthermore, the simulated adsorbates uncovered different complexation interactions that were corroborated by infrared spectroscopy. Therefore, beyond acid-base chemistry, our findings imply that distinct adsorbate structures control antimicrobial trapping within clay nanopores

  17. Complexation of fluoroquinolone antibiotics with human serum albumin: A fluorescence quenching study

    Energy Technology Data Exchange (ETDEWEB)

    Seedher, Neelam, E-mail: nseedher@yahoo.co [Department of Chemistry, Panjab University, Chandigarh 160014 (India); Agarwal, Pooja [Department of Chemistry, Panjab University, Chandigarh 160014 (India)

    2010-10-15

    Mechanism of interaction and detailed physico-chemical characterization of the binding of four fluoroquinolones: levofloxacin, sparfloxacin, ciprofloxacin HCl and enrofloxacin with human serum albumin has been studied at physiological pH (7.4) using fluorescence spectroscopic technique. The stoichiometry of interaction was found to be 1:1 for all the drugs used. The association constants for the interaction were of the order of 10{sup 4} in most cases. At low drug:protein ratios, a significant fraction of the added drug was bound. The predominant interactions involved are hydrogen bonding and Van der Waal's interactions in the case of levofloxacin, hydrophobic interactions in the case of ciprofloxacin hydrochloride and enrofloxacin and hydrogen bonding, hydrophobic and electrostatic interactions in the case of sparfloxacin. The drug binding region did not coincide with that of the hydrophobic probe, 1-anilinonaphthalene-8-sulfonate (ANS). From the displacement of site-specific probes and site-marker drugs, it was concluded that ciprofloxacin hydrochloride is site II-specific while enrofloxacin is a site I-specific drug. Levofloxacin binds at both site I and site II with equal affinity. Sparfloxacin had higher affinity for site II than site I. It is also possible that sparfloxacin binds at the interface between site I and site II. Stern-Volmer analysis of the data showed that the quenching mechanism is predominantly collisional for the binding of ciprofloxacin HCl and enrofloxacin while both static and collisional quenching mechanisms are operative in the case of levofloxacin and sparfloxacin. High magnitude of the rate constant for quenching showed that the process is not entirely diffusion controlled. Circular dichroism (CD) spectroscopic studies showed that the presence of drugs did not cause any major changes in the secondary structure of HSA.

  18. Removal of fluoroquinolone contaminants from environmental waters on sepiolite and its photo-induced regeneration.

    Science.gov (United States)

    Sturini, Michela; Speltini, Andrea; Maraschi, Federica; Profumo, Antonella; Tarantino, Serena; Gualtieri, Alessandro F; Zema, Michele

    2016-05-01

    Sepiolite is studied as sorbent for removal of Fluoroquinolone (FQ) contaminants from water. Marbofloxacin (MAR) and Enrofloxacin (ENR) were chosen as model FQs since they are the two most commonly employed veterinary FQs in livestock farming in northern Italy. Adsorption experiments on two sepiolites (SP-1 and SSE16) were carried out in tap water at pH 7.5 to better mimic real conditions. The sorption experimental data were fitted by Freundlich, Langmuir and S-Logistic1 models. The latter better described MAR and ENR adsorptions. Adsorption capacities of SP-1 and SSE16, respectively, were 132 mg g(-1) and 121 mg g(-1) for MAR, and 112 mg g(-1) and 93 mg g(-1) for ENR. X-ray powder diffraction, performed on clay samples enriched with each FQ and on the pristine clays, showed no substantial differences between the two sepiolites and evidenced no significant structural changes after FQs uptake, as also verified by infrared spectroscopy. This indicates that adsorption occurs only on the external surface of the mineral and not in the intracrystalline microporosity, likely due to the interaction between the FQ carboxylic group and the sepiolite surface. For the first time solid-state photodegradation of the adsorbed FQs was investigated for regenerating the sorbent. Results showed that the adsorbed drugs are effectively photodegraded by solar light, thus allowing sepiolite to be reused. The efficiency of this material for remediation of contaminated water was proved on ditch water, collected downstream a swine farm, containing some tens of ng L(-1) of MAR and ENR. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Impact of Fluoroquinolone Exposure Prior to Tuberculosis Diagnosis on Clinical Outcomes in Immunocompromised Patients.

    Science.gov (United States)

    Lee, Ju Young; Lee, Hyun Jung; Kim, Yong Kyun; Yu, Shinae; Jung, Jiwon; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Shim, Tae Sun; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

    2016-07-01

    There have been concerns about an association of fluoroquinolone (FQ) use prior to tuberculosis (TB) diagnosis with adverse outcomes. However, FQ use might prevent clinical deterioration in missed TB patients, especially in those who are immunocompromised, until they receive definitive anti-TB treatment. All adult immunocompromised patients with smear-negative and culture-positive TB at a tertiary care hospital in Korea over a 2-year period were included in this study. Long-term FQ (≥7 days) use was defined as exposure to FQ for at least 7 days prior to TB diagnosis. A total of 194 patients were identified: 33 (17%) in the long-term FQ group and 161 (83%) in the comparator, including a short-term FQ group (n = 23), non-FQ group (n = 78), and a group receiving no antibiotics (n = 60). Patients in the long-term FQ group presented with atypical chest radiologic pattern more frequently than those in the comparator (77% [24/31] versus 46% [63/138]; P = 0.001). The median time from mycobacterial test to positive mycobacterial culture appeared to be longer in the long-term FQ group (8.1 weeks versus 7.7 weeks; P = 0.09), although the difference was not statistically significant. Patients in the long-term FQ group were less likely to receive empirical anti-TB treatment (55% versus 74%; P = 0.03). The median time from mycobacterial test to anti-TB therapy was longer in the long-term FQ group (4.6 weeks versus 2.2 weeks; P 0.99) or in the 30-day (6% versus 6%; P > 0.99) or 90-day (12% versus 12%; P > 0.99) mortality rate between the two groups. FQ exposure (≥7 days) prior to TB diagnosis in immunocompromised patients appears not to be associated with adverse outcomes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  20. Effects of disruption of heat shock genes on susceptibility of Escherichia coli to fluoroquinolones

    Directory of Open Access Journals (Sweden)

    Morioka Mizue

    2003-08-01

    Full Text Available Abstract Background It is well known that expression of certain bacterial genes responds rapidly to such stimuli as exposure to toxic chemicals and physical agents. It is generally believed that the proteins encoded in these genes are important for successful survival of the organism under the hostile conditions. Analogously, the proteins induced in bacterial cells exposed to antibiotics are believed to affect the organisms' susceptibility to these agents. Results We demonstrated that Escherichia coli cells exposed to levofloxacin (LVFX, a fluoroquinolone (FQ, induce the syntheses of heat shock proteins and RecA. To examine whether the heat shock proteins affect the bactericidal action of FQs, we constructed E. coli strains with mutations in various heat shock genes and tested their susceptibility to FQs. Mutations in dnaK, groEL, and lon increased this susceptibility; the lon mutant exhibited the greatest effects. The increased susceptibility of the lon mutant was corroborated by experiments in which the gene encoding the cell division inhibitor, SulA, was subsequently disrupted. SulA is induced by the SOS response and degraded by the Lon protease. The findings suggest that the hypersusceptibility of the lon mutant to FQs could be due to abnormally high levels of SulA protein resulting from the depletion of Lon and the continuous induction of the SOS response in the presence of FQs. Conclusion The present results show that the bactericidal action of FQs is moderately affected by the DnaK and GroEL chaperones and strongly affected by the Lon protease. FQs have contributed successfully to the treatment of various bacterial infections, but their widespread use and often misuse, coupled with emerging resistance, have gradually compromised their utility. Our results suggest that agents capable of inhibiting the Lon protease have potential for combination therapy with FQs.

  1. Complexation of fluoroquinolone antibiotics with human serum albumin: A fluorescence quenching study

    International Nuclear Information System (INIS)

    Seedher, Neelam; Agarwal, Pooja

    2010-01-01

    Mechanism of interaction and detailed physico-chemical characterization of the binding of four fluoroquinolones: levofloxacin, sparfloxacin, ciprofloxacin HCl and enrofloxacin with human serum albumin has been studied at physiological pH (7.4) using fluorescence spectroscopic technique. The stoichiometry of interaction was found to be 1:1 for all the drugs used. The association constants for the interaction were of the order of 10 4 in most cases. At low drug:protein ratios, a significant fraction of the added drug was bound. The predominant interactions involved are hydrogen bonding and Van der Waal's interactions in the case of levofloxacin, hydrophobic interactions in the case of ciprofloxacin hydrochloride and enrofloxacin and hydrogen bonding, hydrophobic and electrostatic interactions in the case of sparfloxacin. The drug binding region did not coincide with that of the hydrophobic probe, 1-anilinonaphthalene-8-sulfonate (ANS). From the displacement of site-specific probes and site-marker drugs, it was concluded that ciprofloxacin hydrochloride is site II-specific while enrofloxacin is a site I-specific drug. Levofloxacin binds at both site I and site II with equal affinity. Sparfloxacin had higher affinity for site II than site I. It is also possible that sparfloxacin binds at the interface between site I and site II. Stern-Volmer analysis of the data showed that the quenching mechanism is predominantly collisional for the binding of ciprofloxacin HCl and enrofloxacin while both static and collisional quenching mechanisms are operative in the case of levofloxacin and sparfloxacin. High magnitude of the rate constant for quenching showed that the process is not entirely diffusion controlled. Circular dichroism (CD) spectroscopic studies showed that the presence of drugs did not cause any major changes in the secondary structure of HSA.

  2. A novel method to discover fluoroquinolone antibiotic resistance (qnr genes in fragmented nucleotide sequences

    Directory of Open Access Journals (Sweden)

    Boulund Fredrik

    2012-12-01

    Full Text Available Abstract Background Broad-spectrum fluoroquinolone antibiotics are central in modern health care and are used to treat and prevent a wide range of bacterial infections. The recently discovered qnr genes provide a mechanism of resistance with the potential to rapidly spread between bacteria using horizontal gene transfer. As for many antibiotic resistance genes present in pathogens today, qnr genes are hypothesized to originate from environmental bacteria. The vast amount of data generated by shotgun metagenomics can therefore be used to explore the diversity of qnr genes in more detail. Results In this paper we describe a new method to identify qnr genes in nucleotide sequence data. We show, using cross-validation, that the method has a high statistical power of correctly classifying sequences from novel classes of qnr genes, even for fragments as short as 100 nucleotides. Based on sequences from public repositories, the method was able to identify all previously reported plasmid-mediated qnr genes. In addition, several fragments from novel putative qnr genes were identified in metagenomes. The method was also able to annotate 39 chromosomal variants of which 11 have previously not been reported in literature. Conclusions The method described in this paper significantly improves the sensitivity and specificity of identification and annotation of qnr genes in nucleotide sequence data. The predicted novel putative qnr genes in the metagenomic data support the hypothesis of a large and uncharacterized diversity within this family of resistance genes in environmental bacterial communities. An implementation of the method is freely available at http://bioinformatics.math.chalmers.se/qnr/.

  3. The incidence and risk factors of resistant E. coli infections after prostate biopsy under fluoroquinolone prophylaxis: a single-centre experience with 2215 patients.

    Science.gov (United States)

    Kandemir, Özlem; Bozlu, Murat; Efesoy, Ozan; Güntekin, Onur; Tek, Mesut; Akbay, Erdem

    2016-08-01

    We evaluated the incidence and risk factors of resistant Escherichia coli infections after the prostate biopsy under flouroquinolone prophylaxis. From January 2003 to December 2012, we retrospectively evaluated the records of 2215 patients. The risk factors were described for infective complications and resistant E. coli in positive cultures was calculated. Of 2215 patients, 153 had positive urine cultures, such as 129 (84·3%) E. coli, 8 (5·2%) Enterococcus spp., 6 (3·9%) Enterobacter spp., 5 (3·2%) Pseudomonas spp., 3 (1·9%) MRCNS, and 2 (1·3%) Klebsiella spp. Of the positive urine cultures which yielded E. coli, 99 (76·7%) were evaluated for fluoroquinolone resistance. Of those, 83 (83·8%) were fluoroquinolone-resistant and composed of 51 (61·4%) extended-spectrum beta-lactamase (ESBL)-positive. Fluoroquinolone-resistant E. coli ratios were 73·4 and 95·9% before 2008 and after 2008, respectively (P = 0·002). The most sensitive antibiotics for fluoroquinolone-resistant E. coli strains were imipenem (100%), amikacin (84%) and cefoperazone (83%). The use of quinolones in the last 6 months and a history of hospitalization in the last 30 days were found to be significant risk factors. We found that resistant E. coli strains might be a common microorganism in patients with this kind of complication. The risk factors for development of infection with these resistant strains were history of the use of fluoroquinolones and hospitalization.

  4. An Objective Short Sleep Insomnia Disorder Subtype Is Associated With Reduced Brain Metabolite Concentrations In Vivo: A Preliminary Magnetic Resonance Spectroscopy Assessment.

    Science.gov (United States)

    Miller, Christopher B; Rae, Caroline D; Green, Michael A; Yee, Brendon J; Gordon, Christopher J; D'Rozario, Angela L; Kyle, Simon D; Espie, Colin A; Grunstein, Ronald R; Bartlett, Delwyn J

    2017-11-01

    To evaluate brain metabolites in objective insomnia subtypes defined from polysomnography (PSG): insomnia with short sleep duration (I-SSD) and insomnia with normal sleep duration (I-NSD), relative to good sleeping controls (GSCs). PSG empirically grouped insomnia patients into I-SSD (n = 12: mean [SD] total sleep time [TST] = 294.7 minutes [30.5]) or I-NSD (n = 19: TST = 394.4 minutes [34.9]). 1H magnetic resonance spectroscopy (MRS) acquired in the left occipital cortex (LOCC), left prefrontal cortex, and anterior cingulate cortex was used to determine levels of creatine, aspartate, glutamate, and glutamine (referenced to water). Glutathione, glycerophosphocholine, lactate, myoinositol, and N-acetylaspartate measurements were also obtained. Sixteen GSCs were included for comparison. Multivariate analysis of variance was used to evaluate differences in creatine, aspartate, glutamate, and glutamine. Aspartate and glutamine concentrations were reduced in the LOCC in I-SSD compared with I-NSD (both p sleep onset (r = -.40, p sleep study: Australia New Zealand Clinical Trials Registry (ANZCTR): https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12612000050853. 12612000050853. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  5. ramR Mutations Affecting Fluoroquinolone Susceptibility in Epidemic Multidrug-Resistant Salmonella enterica Serovar Kentucky ST198

    Directory of Open Access Journals (Sweden)

    Axel eCloeckaert

    2013-07-01

    Full Text Available A screening for non-target mutations affecting fluoroquinolone susceptibility was conducted in epidemic multidrug-resistant Salmonella enterica serovar Kentucky ST198. Among a panel of representative isolates (n=30, covering the epidemic, only three showed distinct mutations in ramR resulting in enhanced expression of genes encoding the AcrAB-TolC efflux system and low increase in ciprofloxacin MIC. No mutations were detected in other regulatory regions of this efflux system. Ciprofloxacin resistance in serovar Kentucky ST198 is thus currently mainly due to multiple target gene mutations.

  6. Fluoroquinolone-mediated inhibition of cell growth, S-G2/M cell cycle arrest, and apoptosis in canine osteosarcoma cell lines.

    Science.gov (United States)

    Seo, Kyoung won; Holt, Roseline; Jung, Yong-Sam; Rodriguez, Carlos O; Chen, Xinbin; Rebhun, Robert B

    2012-01-01

    Despite significant advancements in osteosarcoma research, the overall survival of canine and human osteosarcoma patients has remained essentially static over the past 2 decades. Post-operative limb-spare infection has been associated with improved survival in both species, yet a mechanism for improved survival has not been clearly established. Given that the majority of canine osteosarcoma patients experiencing post-operative infections were treated with fluoroquinolone antibiotics, we hypothesized that fluoroquinolone antibiotics might directly inhibit the survival and proliferation of canine osteosarcoma cells. Ciprofloxacin or enrofloxacin were found to inhibit p21(WAF1) expression resulting in decreased proliferation and increased S-G(2)/M accumulation. Furthermore, fluoroquinolone exposure induced apoptosis of canine osteosarcoma cells as demonstrated by cleavage of caspase-3 and PARP, and activation of caspase-3/7. These results support further studies examining the potential impact of quinolones on survival and proliferation of osteosarcoma.

  7. Fluoroquinolone-mediated inhibition of cell growth, S-G2/M cell cycle arrest, and apoptosis in canine osteosarcoma cell lines.

    Directory of Open Access Journals (Sweden)

    Kyoung won Seo

    Full Text Available Despite significant advancements in osteosarcoma research, the overall survival of canine and human osteosarcoma patients has remained essentially static over the past 2 decades. Post-operative limb-spare infection has been associated with improved survival in both species, yet a mechanism for improved survival has not been clearly established. Given that the majority of canine osteosarcoma patients experiencing post-operative infections were treated with fluoroquinolone antibiotics, we hypothesized that fluoroquinolone antibiotics might directly inhibit the survival and proliferation of canine osteosarcoma cells. Ciprofloxacin or enrofloxacin were found to inhibit p21(WAF1 expression resulting in decreased proliferation and increased S-G(2/M accumulation. Furthermore, fluoroquinolone exposure induced apoptosis of canine osteosarcoma cells as demonstrated by cleavage of caspase-3 and PARP, and activation of caspase-3/7. These results support further studies examining the potential impact of quinolones on survival and proliferation of osteosarcoma.

  8. Degradation of the fluoroquinolone enrofloxacin by electrochemical advanced oxidation processes based on hydrogen peroxide electrogeneration

    Energy Technology Data Exchange (ETDEWEB)

    Guinea, Elena; Garrido, Jose Antonio; Rodriguez, Rosa Maria; Cabot, Pere-Lluis; Arias, Conchita; Centellas, Francesc [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain); Brillas, Enric, E-mail: brillas@ub.ed [Laboratori d' Electroquimica dels Materials i del Medi Ambient, Departament de Quimica Fisica, Facultat de Quimica, Universitat de Barcelona, Marti i Franques 1-11, 08028 Barcelona (Spain)

    2010-02-15

    Solutions of the veterinary fluoroquinolone antibiotic enrofloxacin in 0.05 M Na{sub 2}SO{sub 4} of pH 3.0 have been comparatively degraded by electrochemical advanced oxidation processes such as anodic oxidation with electrogenerated H{sub 2}O{sub 2} (AO-H{sub 2}O{sub 2}), electro-Fenton (EF), photoelectro-Fenton (PEF) and solar photoelectro-Fenton (SPEF) at constant current density. The study has been performed using an undivided stirred tank reactor of 100 ml and a batch recirculation flow plant of 2.5 l with an undivided filter-press cell coupled to a solar photoreactor, both equipped with a Pt or boron-doped diamond (BDD) anode and a carbon-polytetrafluoroethylene gas diffusion cathode to generate H{sub 2}O{sub 2} from O{sub 2} reduction. In EF, PEF and SPEF, hydroxyl radical (centre dotOH) is formed from Fenton's reaction between added catalytic Fe{sup 2+} and generated H{sub 2}O{sub 2}. Almost total decontamination of enrofloxacin solutions is achieved in the stirred tank reactor by SPEF with BDD. The use of the batch recirculation flow plant showed that this process is the most efficient and can be viable for industrial application, becoming more economic and yielding higher mineralization degree with raising antibiotic content. This is feasible because organics are quickly oxidized with centre dotOH formed from Fenton's reaction and at BDD from water oxidation, combined with the fast photolysis of complexes of Fe(III) with generated carboxylic acids under solar irradiation. The lower intensity of UVA irradiation used in PEF with BDD causes a slower degradation. EF with BDD is less efficient since centre dotOH cannot destroy the most persistent Fe(III)-oxalate and Fe(III)-oxamate complexes. AO-H{sub 2}O{sub 2} with BDD yields the poorest mineralization because pollutants are only removed with centre dotOH generated at BDD. All procedures are less potent using Pt as anode due to the lower production of centre dotOH at its surface. Enrofloxacin

  9. Degradation of the fluoroquinolone enrofloxacin by electrochemical advanced oxidation processes based on hydrogen peroxide electrogeneration

    International Nuclear Information System (INIS)

    Guinea, Elena; Garrido, Jose Antonio; Rodriguez, Rosa Maria; Cabot, Pere-Lluis; Arias, Conchita; Centellas, Francesc; Brillas, Enric

    2010-01-01

    Solutions of the veterinary fluoroquinolone antibiotic enrofloxacin in 0.05 M Na 2 SO 4 of pH 3.0 have been comparatively degraded by electrochemical advanced oxidation processes such as anodic oxidation with electrogenerated H 2 O 2 (AO-H 2 O 2 ), electro-Fenton (EF), photoelectro-Fenton (PEF) and solar photoelectro-Fenton (SPEF) at constant current density. The study has been performed using an undivided stirred tank reactor of 100 ml and a batch recirculation flow plant of 2.5 l with an undivided filter-press cell coupled to a solar photoreactor, both equipped with a Pt or boron-doped diamond (BDD) anode and a carbon-polytetrafluoroethylene gas diffusion cathode to generate H 2 O 2 from O 2 reduction. In EF, PEF and SPEF, hydroxyl radical (·OH) is formed from Fenton's reaction between added catalytic Fe 2+ and generated H 2 O 2 . Almost total decontamination of enrofloxacin solutions is achieved in the stirred tank reactor by SPEF with BDD. The use of the batch recirculation flow plant showed that this process is the most efficient and can be viable for industrial application, becoming more economic and yielding higher mineralization degree with raising antibiotic content. This is feasible because organics are quickly oxidized with ·OH formed from Fenton's reaction and at BDD from water oxidation, combined with the fast photolysis of complexes of Fe(III) with generated carboxylic acids under solar irradiation. The lower intensity of UVA irradiation used in PEF with BDD causes a slower degradation. EF with BDD is less efficient since ·OH cannot destroy the most persistent Fe(III)-oxalate and Fe(III)-oxamate complexes. AO-H 2 O 2 with BDD yields the poorest mineralization because pollutants are only removed with ·OH generated at BDD. All procedures are less potent using Pt as anode due to the lower production of ·OH at its surface. Enrofloxacin decay always follows a pseudo first-order reaction. Its primary aromatic by-products and short intermediates

  10. Structure-activity relationship and role of oxygen in the potential antitumour activity of fluoroquinolones in human epithelial cancer cells.

    Science.gov (United States)

    Perucca, Paola; Savio, Monica; Cazzalini, Ornella; Mocchi, Roberto; Maccario, Cristina; Sommatis, Sabrina; Ferraro, Daniela; Pizzala, Roberto; Pretali, Luca; Fasani, Elisa; Albini, Angelo; Stivala, Lucia Anna

    2014-11-01

    The photobehavior of ciprofloxacin, lomefloxacin and ofloxacin fluoroquinolones was investigated using several in vitro methods to assess their cytotoxic, antiproliferative, and genotoxic potential against two human cancer cell lines. We focused our attention on the possible relationship between their chemical structure, O₂ partial pressure and photobiological activity on cancer cells. The three molecules share the main features of most fluoroquinolones, a fluorine in 6 and a piperazino group in 7, but differ at the key position 8, unsubstituted in ciprofloxacin, a fluorine in lomefloxacin and an alkoxy group in ofloxacin. Studies in solution show that ofloxacin has a low photoreactivity; lomefloxacin reacts via aryl cation, ciprofloxacin reacts but not via the cation. In our experiments, ciprofloxacin and lomefloxacin showed a high and comparable potential for photodamaging cells and DNA. Lomefloxacin appeared the most efficient molecule in hypoxia, acting mainly against tumour cell proliferation and generating DNA plasmid photocleavage. Although our results do not directly provide evidence that a carbocation is involved in photodamage induced by lomefloxacin, our data strongly support this hypothesis. This may lead to new and more efficient anti-tumour drugs involving a cation in their mechanism of action. This latter acting independently of oxygen, can target hypoxic tumour tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Efficacy of Fluoroquinolone/Probiotic Combination Therapy for Recurrent Urinary Tract Infection in Children: A Retrospective Analysis.

    Science.gov (United States)

    Madden-Fuentes, Ramiro J; Arshad, Mehreen; Ross, Sherry S; Seed, Patrick C

    2015-09-01

    Children with normal urinary tract anatomy and function and highly recurrent urinary tract infection (rUTI) may have a lack of alternatives when antibiotic prophylaxis and "watchful waiting" approaches fail. This retrospective review reports the outcomes in children who received a fluoroquinolone/probiotic combination in an attempt to quantify a reduction in rUTI that was perceived by both clinicians and patients' families. Data from all children with rUTIs previously managed with a fluoroquinolone/probiotic combination at the Pediatric Infectious Diseases Clinic at Duke University Medical Center (Durham, North Carolina) were identified and analyzed. Data from 10 children were eligible for inclusion. Compared with before therapy initiation, total UTI episodes were significantly fewer after therapy initiation (57 vs 4; P = 0.0001). Seven (70%) were free of rUTIs during the follow-up period. Of the 8 patients with known compliance, 7 (88%) were free of rUTIs. Given the chronic nature of these patients' symptoms, the significant decrease in UTI after the initiation of therapy, and the increase in the interval without an infection and/or its symptoms, this treatment regimen has the potential to improve overall quality of life, decrease antibiotic courses, and decrease health care costs in children with rUTI. These results will be validated with a larger cohort of patients in a prospective, randomized trial. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  12. Eliminação de resistência a drogas por fluorquinolonas em Staphylococcus aureus de origem bovina Elimination of resistance to drugs by fluoroquinolones in bovine strains of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Maria S.V. Pereira

    2004-03-01

    Full Text Available Cepas de Staphylococcus aureus de origem bovina foram submetidas ao tratamento com quatro fluoquinolonas na concentração subinibitória (1/2 x CMI, para avaliar a influência desses agentes sobre plasmídios. A ciprofloxacina mostrou ser a fluorquinolona mais eficiente, eliminando marcas de resistência para estreptomicina, tetraciclina, penicilina e cádmio. A norfloxacina e a pefloxacina eliminaram resistência para penicilina e tetraciclina, respectivamente; no entanto, não foi evidenciada a eliminação de plasmídio com ofloxacina. Os resultados confirmam a eficácia das fluor-quinolonas em eliminar plasmídios de resistência mostrando a importância desses estudos como contribuição para o entendimento da prevenção de linhagens multiresistentes, uma vez que as quinolonas em concentrações subinibitórias podem aumentar a sensibilidade das linhagens a outros agentes antimicrobianos.Bovine strains of Staphylococcus aureus were submitted to treatment with four fluoro-quinolones in subinhibitory concentrations (1/2 x MICs to evaluate their influence on the curing of plasmids. Ciprofloxacin showed to be the most efficient by eliminating resistance to streptomycin, tetracyclin, penicillin, and cadmium nitrate. Norfloxacin and pefloxacin eliminated penicillin- and tetracyclin-resistance respectively. Otherwise, plasmids elimination by ofloxacin was not evidenced. The results obtained in this study confirm the potential of fluoroquinolones to eliminate antibiotic-resistant plasmids, and showed to be a valuable contribution for the prevention of multi-resistant strains, and may even enhance their sensitivity to other chemotherapeutic agents.

  13. In vitro and in vivo evaluation of [18F]ciprofloxacin for the imaging of bacterial infections with PET

    International Nuclear Information System (INIS)

    Langer, Oliver; Brunner, Martin; Zeitlinger, Markus; Mueller, Ulrich; Lackner, Edith; Joukhadar, Christian; Mueller, Markus; Ziegler, Sophie; Minar, Erich; Dobrozemsky, Georg; Mitterhauser, Markus; Wadsak, Wolfgang; Dudczak, Robert; Kletter, Kurt

    2005-01-01

    The suitability of the 18 F-labelled fluoroquinolone antibiotic ciprofloxacin ([ 18 F]ciprofloxacin) for imaging of bacterial infections with positron emission tomography (PET) was assessed in vitro and in vivo. For the in vitro experiments, suspensions of various E. colistrains were incubated with different concentrations of [ 18 F]ciprofloxacin (0.01-5.0 μg/ml) and radioactivity retention was measured in a gamma counter. For the in vivo experiments, 725 ± 9 MBq [ 18 F]ciprofloxacin was injected intravenously into four patients with microbiologically proven bacterial soft tissue infections of the lower extremities and time-radioactivity curves were recorded in infected and uninfected tissue for 5 h after tracer injection. Binding of [ 18 F]ciprofloxacin to bacterial cells was rapid, non-saturable and readily reversible. Moreover, bacterial binding of the agent was similar in ciprofloxacin-resistant and ciprofloxacin-susceptible clinical isolates. These findings suggest that non-specific binding rather than specific binding to bacterial type II topoisomerase enzymes is the predominant mechanism of bacterial retention of the radiotracer. PET studies in the four patients with microbiologically proven bacterial soft tissue infections demonstrated locally increased radioactivity uptake in infected tissue, with peak ratios between infected and uninfected tissue ranging from 1.8 to 5.5. Radioactivity was not retained in infected tissue and appeared to wash out with a similar elimination half-life as in uninfected tissue, suggesting that the kinetics of [ 18 F]ciprofloxacin in infected tissue are governed by increased blood flow and vascular permeability due to local infection rather than by a binding process. Taken together, our results indicate that [ 18 F]ciprofloxacin is not suited as a bacteria-specific infection imaging agent for PET. (orig.)

  14. Determination of fluoroquinolone antibiotics in environmental water samples based on magnetic molecularly imprinted polymer extraction followed by liquid chromatography-tandem mass spectrometry

    International Nuclear Information System (INIS)

    Chen Ligang; Zhang Xiaopan; Xu Yang; Du Xiaobo; Sun Xin; Sun Lei; Wang Hui; Zhao Qi; Yu Aimin; Zhang Hanqi; Ding Lan

    2010-01-01

    A simple method based on magnetic separation for selective extraction of fluoroquinolones (FQs) from environmental water samples has been developed using magnetic molecularly imprinted polymer (MMIP) as sorbent. The MMIP has been prepared using ciprofloxacin as template molecule, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linking agent and Fe 3 O 4 magnetite as magnetic component. The polymer has been characterized by scanning electron microscopy, Fourier-transform infrared spectrometry and vibrating sample magnetometry. Various parameters affecting the extraction efficiency were evaluated in order to achieve optimal concentration and reduce non-specific interactions. The analytes desorbed from the polymers were determined by liquid chromatography-tandem mass spectrometry. The matrix effect was evaluated by using different washing solvents for removing interfering compounds from the MMIPs after sample loading. Under the optimal conditions, the linearity of the method obtained is in the range of 20-2000 ng L -1 . The detection limits of FQs are in the range of 3.2-6.2 ng L -1 . The relative standard deviations of intra- and inter-day tests ranging from 2.5 to 7.2% and from 3.6 to 9.1% are obtained. In all three spiked levels (20, 100 and 200 ng L -1 ), the recoveries of FQs are in the range of 76.3-94.2%. The proposed method was successfully applied to determine FQs including ciprofloxacin, enrofloxacin, lomefloxacin, levofloxacin, fleroxacin and sparfloxacin in different water samples, such as lake water, river water, primary and final sewage effluent. Ciprofloxacin and fleroxacin were found in primary and final sewage effluent samples with the contents in the range of 26-87 ng L -1 .

  15. Determination of fluoroquinolone antibiotics in environmental water samples based on magnetic molecularly imprinted polymer extraction followed by liquid chromatography-tandem mass spectrometry

    Energy Technology Data Exchange (ETDEWEB)

    Chen Ligang; Zhang Xiaopan; Xu Yang [College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, Jilin (China); Du Xiaobo; Sun Xin [College of Physics, Jilin University, 2699 Qianjin Street, Changchun 130012 (China); Sun Lei; Wang Hui; Zhao Qi; Yu Aimin; Zhang Hanqi [College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, Jilin (China); Ding Lan, E-mail: dinglan@jlu.edu.cn [College of Chemistry, Jilin University, 2699 Qianjin Street, Changchun 130012, Jilin (China)

    2010-03-03

    A simple method based on magnetic separation for selective extraction of fluoroquinolones (FQs) from environmental water samples has been developed using magnetic molecularly imprinted polymer (MMIP) as sorbent. The MMIP has been prepared using ciprofloxacin as template molecule, methacrylic acid as functional monomer, ethylene glycol dimethacrylate as cross-linking agent and Fe{sub 3}O{sub 4} magnetite as magnetic component. The polymer has been characterized by scanning electron microscopy, Fourier-transform infrared spectrometry and vibrating sample magnetometry. Various parameters affecting the extraction efficiency were evaluated in order to achieve optimal concentration and reduce non-specific interactions. The analytes desorbed from the polymers were determined by liquid chromatography-tandem mass spectrometry. The matrix effect was evaluated by using different washing solvents for removing interfering compounds from the MMIPs after sample loading. Under the optimal conditions, the linearity of the method obtained is in the range of 20-2000 ng L{sup -1}. The detection limits of FQs are in the range of 3.2-6.2 ng L{sup -1}. The relative standard deviations of intra- and inter-day tests ranging from 2.5 to 7.2% and from 3.6 to 9.1% are obtained. In all three spiked levels (20, 100 and 200 ng L{sup -1}), the recoveries of FQs are in the range of 76.3-94.2%. The proposed method was successfully applied to determine FQs including ciprofloxacin, enrofloxacin, lomefloxacin, levofloxacin, fleroxacin and sparfloxacin in different water samples, such as lake water, river water, primary and final sewage effluent. Ciprofloxacin and fleroxacin were found in primary and final sewage effluent samples with the contents in the range of 26-87 ng L{sup -1}.

  16. Magnetic copper-based metal organic framework as an effective and recyclable adsorbent for removal of two fluoroquinolone antibiotics from aqueous solutions.

    Science.gov (United States)

    Wu, Gege; Ma, Jiping; Li, Shuang; Guan, Jing; Jiang, Bo; Wang, Liyan; Li, Jinhua; Wang, Xiaoyan; Chen, Lingxin

    2018-05-30

    Fe 3 O 4 /HKUST-1 magnetic copper based metal-organic frameworks (MOF) were synthesized by a simple and facile method and applied as an effective and recyclable adsorbent for the adsorptive removal of two widely used ciprofloxacin (CIP) and norfloxacin (NOR) fluoroquinolone antibiotics (FQAs) from aqueous solutions. Fe 3 O 4 /HKUST-1 was thoroughly characterized, and the major influence factors including solution pH, adsorbent amount and salt concentration were investigated. Compared to the reported adsorbents, Fe 3 O 4 /HKUST-1 has a very high adsorption rate, and it is found that CIP and NOR could be removed within 30 min. Moreover, the maximum adsorption capacities of the magnetic composites toward CIP and NOR reached as high as 538 mg g -1 and 513 mg g -1 , respectively, much higher than those of most of the reported adsorbents for these two FQAs. The saturation magnetization value of Fe 3 O 4 /HKUST-1 was 44 emu g -1 , which was sufficient for the separation of the Fe 3 O 4 /HKUST-1adsorbent from the aqueous solution by the application of an external magnetic field. Additionally, this magnetic material showed a good reusability with the adsorption capability decreasing only slightly after reuse for ten cycles. These results indicated that the magnetic composites Fe 3 O 4 /HKUST-1 may be a promising adsorbent in the decontamination of FQAs from wastewater due to its high adsorption capability, fast kinetics, easy separation from water, and excellent recyclability. The adsorption mechanism was proposed based on the effects of pH on adsorption and on the zeta potential of the adsorbent. For the adsorption of CIP and NOR by Fe 3 O 4 /HKUST-1, both electrostatic and π-π interactions may be important. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Changes in qnr Prevalence and Fluoroquinolone Resistance in Clinical Isolates of Klebsiella pneumoniae and Enterobacter spp. Collected from 1990 to 2005▿

    Science.gov (United States)

    Strahilevitz, Jacob; Engelstein, Dalia; Adler, Amos; Temper, Violeta; Moses, Allon E.; Block, Colin; Robicsek, Ari

    2007-01-01

    Clinical isolates of Klebsiella pneumoniae and Enterobacter spp. collected from 1990 through 2005 at a tertiary care center were studied for qnr genes. Isolates bearing these genes emerged in the mid-1990s, coinciding with the time of a rapid increase in fluoroquinolone resistance. Sixty percent of these isolates were ciprofloxacin susceptible by CLSI breakpoints. PMID:17526754

  18. Impact of preoperative screening for rectal colonization with fluoroquinolone-resistant enteric bacteria on the incidence of sepsis following transrectal ultrasound guided prostate biopsy

    Directory of Open Access Journals (Sweden)

    Farrell JJ

    2017-02-01

    Full Text Available John J Farrell,1,2 Jennifer L Hicks,3 Stephanie E Wallace,2 Allen D Seftel4,5 1Department of Medicine, Division of Infectious Diseases, University of Illinois College of Medicine, 2Department of Laboratory Medicine, Division of Clinical Microbiology & Serology, OSF/Saint Francis Medical Center, 3Department of Urology, OSF /Saint Francis Medical Center, Peoria, IL, 4Department of Urology, Cooper University Hospital, 5Department of Surgery, Cooper University School of Medicine, Camden, NJ, USA Abstract: With the universal adoption of antibiotic prophylaxis prior to prostate biopsy, the current risk of post-biopsy infection (including sepsis is <2%. Preoperative prophylactic antibiotic regimens can vary, and although fluoroquinolones have emerged as the standard of care, there is no universally agreed upon preoperative antibiotic regimen. Recently, an increase in the proportion of postoperative infections caused by fluoroquinolone-resistant Escherichia coli (as well as other Enterobacteriaceae has led to the exploration of simple, practical, and cost-effective methods to minimize this postoperative infection risk. We performed a prospective, nonrandomized, controlled study of preoperative rectal cultures to screen for rectal colonization with fluoroquinolone-resistant bacteria using ciprofloxacin-supplemented MacConkey agar culture media. To evaluate the feasibility and practicality of this test, one provider used the results of rectal swab cultures collected during the preoperative outpatient evaluation to adjust each patient’s preoperative antibiotic prophylaxis when fluoroquinolone-resistant enteric bacteria were detected, whereas two other providers continued usual preoperative care and empiric antimicrobial prophylaxis. Rectal colonization with fluoroquinolone-resistant bacteria was detected in 19/152 (12.5% of patients. In our intention-to-treat analysis (N=268, the rate of post-biopsy sepsis was 3.6% lower in the group that was screened

  19. Is 5 days of oral fluoroquinolone enough for acute uncomplicated pyelonephritis? The DTP randomized trial.

    Science.gov (United States)

    Dinh, A; Davido, B; Etienne, M; Bouchand, F; Raynaud-Lambinet, A; Aslangul-Castier, E; Szwebel, T A; Duran, C; Der Sahakian, G; Jordy, C; Ranchoux, X; Sembach, N; Mathieu, E; Davido, A; Salomon, J; Bernard, L

    2017-08-01

    The treatment duration of acute uncomplicated pyelonephritis (AUP) is still under debate. As shortening treatment duration could be a means to reduce antimicrobial resistance, we aimed to establish whether 5 days of antibiotic treatment is non-inferior to 10 days in patients with AUP. We performed an open-label prospective randomized trial comparing 5 days to 10 days of fluoroquinolone treatment for AUP. The inclusion criteria were: female patients aged ≥18 years with clinical signs of urinary tract infection, fever >38 °C, and positive urinalysis. Patients were randomized to either 5 or 10 days of fluoroquinolone treatment. Outcome was cure at day 10 and day 30 after the end of treatment. One hundred patients were randomized and 12 were excluded after randomization. The mean ± standard deviation (SD) age was 31.8 ± 11 years old and the mean ± SD temperature was 38.6 ± 0.7 °C. The main bacterium involved was Escherichia coli (n = 86; 97.7%) and 3 (3.4%) patients had a positive blood culture. In the post-hoc analysis, clinical cure 10 days after the end of the treatment was 28/30 (93.3%) in the 5-day arm and 36/38 (94.7%) in the 10-day arm (p = 1.00). At day 30, the clinical cure rate was 23/23 (100%) in the 5-day arm and 20/20 (100%) in the 10-day arm (p = 1.00). The microbiological cure rate was 20/23 (87.0%) in the 5-day arm and 16/20 (80.0%) in the 10-day arm (p = 1.00). The efficacy of 5 days of fluoroquinolone treatment does not seem different from 10 days of treatment for AUP.

  20. Rapid diagnosis of drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol using genotype MTBDRsl assay: a meta-analysis.

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    Yan Feng

    Full Text Available BACKGROUND: There are urgent needs for rapid and accurate drug susceptibility testing of M. tuberculosis. GenoType MTBDRsl is a new molecular kit designed for rapid identification of the resistance to the second-line antituberculosis drugs with a single strip. In recent years, it has been evaluated in many settings, but with varied results. The aim of this meta-analysis was to synthesize the latest data on the diagnostic accuracy of GenoType MTBDRsl in detecting drug resistance to fluoroquinolones, amikacin, capreomycin, kanamycin and ethambutol, in comparison with the phenotypic drug susceptibility test. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guideline. The search terms of "MTBDRsl" and "tuberculosis" were used on PubMed, EMBASE, and Web of Science. QUADAS-2 was used to assess the quality of included studies. Data were analyzed by Meta-Disc 1.4. We calculated the sensitivity, specificity, positive likelihood ratio (PLR, negative likelihood ratio (NLR, diagnostic odds ratio (DOR and corresponding 95% confidence interval (CI for each study. From these calculations, forest plots and summary receiver operating characteristic (SROC curves were produced. RESULTS: Patient selection bias as well as flow and timing bias were observed in most studies. The summarized sensitivity (95% CI was 0.874(0.845-0.899, 0.826(0.777-0.869, 0.820(0.772-0.862, 0.444(0.396-0.492, and 0.679(0.652-0.706 for fluoroquinolones, amikacin, capreomycin, kanamycin, and ethambutol, respectively. The specificity (95% CI was 0.971(0.961-0.980, 0.995(0.987-0.998, 0.973(0.963-0.981, 0.993(0.985-0.997, and 0.799(0.773-0.823, respectively. The AUC (standard error were 0.9754(0.0203, 0.9300(0.0598, 0.9885(0.0038, 0.9689(0.0359, and 0.6846(0.0550, respectively. CONCLUSION: Genotype MTBDRsl showed good accuracy for detecting drug resistance to fluoroquinolones, amikacin and capreomycin, but it may not be an

  1. Overexpression of the novel MATE fluoroquinolone efflux pump FepA in Listeria monocytogenes is driven by inactivation of its local repressor FepR.

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    François Guérin

    Full Text Available Whereas fluoroquinolone resistance mainly results from target modifications in gram-positive bacteria, it is primarily due to active efflux in Listeria monocytogenes. The aim of this study was to dissect a novel molecular mechanism of fluoroquinolone resistance in this important human pathogen. Isogenic L. monocytogenes clinical isolates BM4715 and BM4716, respectively susceptible and resistant to fluoroquinolones, were studied. MICs of norfloxacin and ciprofloxacin were determined in the presence or in the absence of reserpine (10 mg/L. Strain BM4715 was susceptible to norfloxacin (MIC, 4 mg/L and ciprofloxacin (MIC, 0.5 mg/L whereas BM4716 was highly resistant to both drugs (MICs 128 and 32 mg/L, respectively. Reserpine was responsible for a 16-fold decrease in both norfloxacin and ciprofloxacin MICs against BM4716 suggesting efflux associated resistance. Whole-genome sequencing of the strains followed by comparative genomic analysis revealed a single point mutation in the gene for a transcriptional regulator, designated fepR (for fluoroquinolone efflux protein regulator belonging to the TetR family. The frame-shift mutation was responsible for the introduction of a premature stop codon resulting in an inactive truncated protein. Just downstream from fepR, the structural gene for an efflux pump of the MATE family (named FepA was identified. Gene expression was quantified by qRT-PCR and demonstrated that fepA expression was more than 64-fold higher in BM4716 than in BM4715. The clean deletion of the fepR gene from BM4715 was responsible for an overexpression of fepA with resistance to norfloxacin and ciprofloxacin, confirming the role of FepR as a local repressor of fepA. In conclusion, we demonstrated that overexpression of the new MATE efflux pump FepA is responsible for fluoroquinolone resistance in L. monocytogenes and secondary to inactivation of the FepR repressor.

  2. Novel fluoroquinolone derivatives bearing N-thiomide linkage with 6-substituted-2-aminobenzothiazoles: Synthesis and antibacterial evaluation

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    Prabodh Chander Sharma

    2017-02-01

    Full Text Available A series of novel fluoroquinolone derivatives bearing N-thiomide linkage with 6-substituted-2-aminobenzothiazole substituents at the C-7 position were synthesized to obtain potent analogs active against bacterial strains. Some compounds exhibited excellent antibacterial activity against Staphylococcus auerus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa bacterial strains. Among all the synthesized compounds 6-nitro substituted benzothiazole along with norfloxacin (4b and gatifloxacin (4l showed MIC 05 μg/ml when tested against S. auerus. Moreover, compounds 4d, 4f and 4l showed superior MIC (15, 10, and 15 μg/ml respectively against B. subtilis. The results of the present study reveal that the compounds have significant antibacterial potential and are suitable candidates for further exploration.

  3. New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Linke; Na, Guangshui [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Siyu [Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016 (China); Li, Kai [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Peng, E-mail: pzhang@nmemc.org.cn [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Ren, Honglei; Yao, Ziwei [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China)

    2015-09-15

    The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (t{sub d,E}) and hydroxyl-radical oxidation half-lives (t{sub ·OH,E}) in sunlit surface waters. The t{sub d,E} values range from 0.56 min to 28.8 min at 45° N latitude, whereas t{sub ·OH,E} ranges from 3.24 h to 33.6 h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. - Highlights: • It is first reported on hydroxyl-radical oxidation of 6 fluoroquinolone antibiotics. • Methods were developed to assess photolysis and oxidation fate in surface waters. • The neutral form reacted faster with hydroxyl radical than protonated forms. • The main oxidation intermediates and transformation pathways were clarified. • The antibacterial activity changes depend on dominant photolysis pathways.

  4. New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes

    International Nuclear Information System (INIS)

    Ge, Linke; Na, Guangshui; Zhang, Siyu; Li, Kai; Zhang, Peng; Ren, Honglei; Yao, Ziwei

    2015-01-01

    The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (t d,E ) and hydroxyl-radical oxidation half-lives (t ·OH,E ) in sunlit surface waters. The t d,E values range from 0.56 min to 28.8 min at 45° N latitude, whereas t ·OH,E ranges from 3.24 h to 33.6 h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. - Highlights: • It is first reported on hydroxyl-radical oxidation of 6 fluoroquinolone antibiotics. • Methods were developed to assess photolysis and oxidation fate in surface waters. • The neutral form reacted faster with hydroxyl radical than protonated forms. • The main oxidation intermediates and transformation pathways were clarified. • The antibacterial activity changes depend on dominant photolysis pathways

  5. Analysis of mutations in DNA gyrase and topoisomerase IV of Ureaplasma urealyticum and Ureaplasma parvum serovars resistant to fluoroquinolones.

    Science.gov (United States)

    Piccinelli, Giorgio; Gargiulo, Franco; Biscaro, Valeria; Caccuri, Francesca; Caruso, Arnaldo; De Francesco, Maria Antonia

    2017-01-01

    This study aims to determine the prevalence of fluoroquinolone resistance of Ureaplasma biovars and serovars isolated from urogenital clinical samples and determine the underlying molecular mechanism for quinolone resistance for all resistant isolates. Of 105 samples confirmed as positive for U. urealyticum/U. parvum, 85 were resistant to quinolones by the Mycoplasma-IST2 kit. However, only 43 out of 85 quinolone resistant isolates had amino acid substitutions in GyrA, GyrB, ParC and ParE proteins underlining that this assay have mis-identified as fluoroquinolone resistant 42 isolates. The known ParC E87K and ParC S83L mutations were found in 1 and 10 isolates, respectively. An original mutation of ureaplasmal ParC (E87Q, 1 isolate) was found. Furthermore, we found a ParE R448K mutation in one isolate, already described. Among the additional alterations detected, the most prevalent mutation found was L176F in GyrA protein in 18 isolates with single infection and in 3 isolates with mixed ureaplasma infections. Mutations in GyrB (E502Q, 4 isolates), ParE (Q412K, Q412P, Q412T, 3 independent isolates), whose role is unknown, were also found. Other sporadic mutations in the four genes were identified. This investigation is the result of monitoring the data for molecular fluoroquinone resistance in Ureaplasma spp. in Italy. Resulting that this acquired resistance is high and that continued local epidemiological studies are essential to monitor and document their antimicrobial resistance trends. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Aluminium sensitized spectrofluorimetric determination of fluoroquinolones in milk samples coupled with salting-out assisted liquid-liquid ultrasonic extraction

    Science.gov (United States)

    Xia, Qinghai; Yang, Yaling; Liu, Mousheng

    2012-10-01

    An aluminium sensitized spectrofluorimetric method coupled with salting-out assisted liquid-liquid ultrasonic extraction for the determination of four widely used fluoroquinolones (FQs) namely norfloxacin (NOR), ofloxacin (OFL), ciprofloxacin (CIP) and gatifloxacin (GAT) in bovine raw milk was described. The analytical procedure involves the fluorescence sensitization of aluminium (Al3+) by complexation with FQs, salting-out assisted liquid-liquid ultrasonic extraction (SALLUE), followed by spectrofluorometry. The influence of several parameters on the extraction (the salt species, the amount of salt, pH, temperature and phase volume ratio) was investigated. Under optimized experimental conditions, the detection limits of the method in milk varied from 0.009 μg/mL for NOR to 0.016 μg/mL for GAT (signal-to-noise ratio (S/N) = 3). The relative standard deviations (RSD) values were found to be relatively low (0.54-2.48% for four compounds). The calibration graph was linear from 0.015 to 2.25 μg/mL with coefficient of determinations not less than 0.9974. The methodology developed was applied to the determination of FQs in bovine raw milk samples. The main advantage of this method is simple, accurate and green. The method showed promising applications for analyzing polar analytes especially polar drugs in various sample matrices.

  7. [Impact of corrective measures on fluoroquinolones prescriptions for urinary tract infections during a 2-round relevance study].

    Science.gov (United States)

    Gendrin, V; Letranchant, L; Hénard, S; Frentiu, E; Demore, B; Burty, C; May, T; Doco-Lecompte, T

    2012-01-01

    Evaluating the impact of corrective measures on fluoroquinolones (FQ) prescriptions for urinary tract infections (UTI) during a 2-round relevance study on a regional scale. FQ prescriptions of voluntary hospitals were checked by an infectious diseases physician and a pharmacist according to regional guidelines. A first round (R1) took place in January 2008, with feedback and proposal for personalized corrective measures in January 2009. A second round (R2) was organized in June 2009. UTI data were extracted and the results of the two rounds were compared. Four hundred and thirty-five and 302 FQ prescriptions for UTI, coming from 28 and 24 different hospitals, were analyzed at R1 and R2, respectively. Thirty-six percent and 55% of these prescriptions were entirely in accordance with regional guidelines, at respectively R1 and R2 (PUTI through better adhesion to the regional guidelines between the two rounds. This is probably due to first turn results feedback, and corrective measures suggestion. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  8. Deciphering the complexation process of a fluoroquinolone antibiotic, levofloxacin, with bovine serum albumin in the presence of additives

    Science.gov (United States)

    Kaur, Amandeep; Khan, Imran Ahmd; Banipal, Parampaul Kaur; Banipal, Tarlok Singh

    2018-02-01

    The current work aims to explore the thermodynamic and conformational aspects for the binding of fluoroquinolone antibacterial drug, levofloxacin (LFC), with bovine serum albumin (BSA) using calorimetric, spectroscopic (UV-visible, fluorescence, circular dichroism, and 1H NMR), dynamic light scattering (DLS) and computational methods (molecular docking). The binding of LFC with BSA at two sequential sites with higher affinity ( 103 M- 1) at the first site has been explored by calorimetry whereas the binding at a single site with affinity of the order of 104 M- 1 has been observed from fluorescence spectroscopy. The calorimetric study in the presence of additives along with docking analysis reveals the significant role of electrostatic, hydrogen bonding, and hydrophobic interactions in the association process. The slight conformational changes in protein as well as the changes in the water network structure around the binding cavity of protein have been observed from spectroscopic and DLS measurements. The LFC induced quenching of BSA fluorescence was observed to be initiated mainly through the static quenching process and this suggests the formation of ground state LFC-BSA association complex. The stronger interactions of LFC in the cavity of Sudlow site I (subdomain IIA) of protein have been explored from site marker calorimetric and molecular docking study.

  9. New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes.

    Science.gov (United States)

    Ge, Linke; Na, Guangshui; Zhang, Siyu; Li, Kai; Zhang, Peng; Ren, Honglei; Yao, Ziwei

    2015-09-15

    The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (td,E) and hydroxyl-radical oxidation half-lives (tOH,E) in sunlit surface waters. The td,E values range from 0.56 min to 28.8 min at 45° N latitude, whereas tOH,E ranges from 3.24h to 33.6h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. Copyright © 2015. Published by Elsevier B.V.

  10. Should patients with acute exacerbation of chronic bronchitis be treated with antibiotics? Advantages of the use of fluoroquinolones.

    Science.gov (United States)

    Mensa, J; Trilla, A

    2006-05-01

    The pathological changes in chronic bronchitis (CB) produce airflow obstruction, reduce the effectiveness of the mucocilliary drainage system and lead to bacterial colonisation of bronchial secretion. The presence of bacteria induces an inflammatory response mediated by leukocytes. There is a direct relationship between the degree of impairment of the mucocilliary drainage system, the density of bacteria in mucus and the number of leukocytes in the sputum. Purulent sputum is a good marker of a high bacterial load. Eventually, if the number of leukocytes is high, their normal activity could decrease the effectiveness of the drainage system, increase the bronchial obstruction and probably damage the lung parenchyma. Whenever the density of bacteria in the bronchial lumen is >or=10(6) CFU/mL, there is a high probability that the degree of inflammatory response will lead to a vicious cycle which in turn tends to sustain the process. This situation can arise during the clinical course of any acute exacerbation of CB, independently of its aetiology, provided the episode is sufficiently severe and/or prolonged. Fluoroquinolones of the third and fourth generation are bactericidal against most microorganisms usually related to acute exacerbations of CB. Their diffusion to bronchial mucus is adequate. When used in short (5-day) treatment they reduce the bacterial load in a higher proportion than is achieved by beta-lactam or macrolide antibiotics given orally. Although the clinical cure rate is similar to that obtained with other antibiotics, the time between exacerbations could be increased.

  11. Fluoroquinolone Resistance Mechanisms and population structure of Enterobacter cloacae non-susceptible to Ertapenem in North-Eastern France.

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    Thomas eGuillard

    2015-10-01

    Full Text Available Fluoroquinolone (FQ agents are a potential resort to treat infection due to Enterobacteriaceae producing extended spectrum β-lactamase and susceptible to FQ. In a context of increase of non-susceptibility to carbapenems among Enterobacteriaceae, we characterized FQ resistance mechanisms in 75 Enterobacter cloacae isolates non-susceptible to ertapenem in North-Eastern France in 2012 and describe the population structure by pulsed field gel electrophoresis (PFGE and multilocus sequence typing (MLST.Among them, 14.7% (12/75 carried a carbapenemase-encoding gene. Except one isolate producing VIM-1, the carbapenemase-producing isolates carried the well-known IncL/M pOXA48a plasmid. Most of the isolates (59/75 harbored at least a FQ-R determinant. qnr genes were predominant (40%, 30/75. The MLST study revealed that E. cloacae isolates’ clonality was wide (24 different STs. The more widespread STs were ST74, ST101, ST110, ST114 and ST133. Carbapenem MICs were higher for E. cloacae ST74 than for other E. cloacae isolates. PMQR determinants were more often observed in E. cloacae ST74 isolates. These findings showed that (i pOXA-48a is spreading in North-Eastern France, (ii qnr is preponderant in E. cloacae, (iii E. cloacae comprised a large amount of lineages spreading in North-Eastern France and (iv FQ as an alternative to β-lactams to treat ertapenem non-susceptible Enterobacteriaceae are compromised.

  12. SYNTHESIS AND ANTIMICROBIAL ACTIVITIES OF NEW 1,2,4- TRIAZOLES, MANNICH BASES, CONAZOLES, AND FLUOROQUINOLONES

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    Şule CEYLAN

    2016-09-01

    Full Text Available Abstract: Triazoles are heterocyclic compounds which have been of interest in the development of novel compounds with antidepressant, anti-inflammatory, analgesic, antibacterial, antimycobacterial, antifungal, antiviral, anticancer, and other activities. In this article, a series of fluorine- and piperazine-containing some novel biologically active 1,2,4-triazole-3-one derivatives were synthesized by the Mannich reaction of triazole intermediates. The structures for novel synthesized compounds were elucidated using elemental analysis and FT IR, 13C NMR, 1H NMR, EI MS techniques. These compounds were investigated in vitro for their antimicrobial properties and several compounds have fungicidal activity against Candida albicans and Saccharomyces cerevisiae. And also some of the compounds exhibited excellent activity on Mycobacterium smegmatis, a nonpigmented fast-rising mycobacterium, at the concentration of <1 μg/mL is better than standard drug streptomycin.

  13. Contribution of different mechanisms to the resistance to fluoroquinolones in clinical isolates of Salmonella enterica

    Directory of Open Access Journals (Sweden)

    Abeer Ahmed Rushdy

    Full Text Available OBJECTIVES: To study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates. METHODS: Antimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated. RESULTS: Five Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F. Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2-4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC. CONCLUSIONS: Efflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gramnegative clinical isolates.

  14. Isolation of novel IncA/C and IncN fluoroquinolone resistance plasmids from an antibiotic-polluted lake.

    Science.gov (United States)

    Flach, Carl-Fredrik; Johnning, Anna; Nilsson, Ida; Smalla, Kornelia; Kristiansson, Erik; Larsson, D G Joakim

    2015-10-01

    Antibiotic-polluted environments may function as reservoirs for novel resistance plasmids not yet encountered in pathogens. The aims of this study were to assess the potential of resistance transfer between bacteria from such environments and Escherichia coli, and to characterize the conjugative elements involved. Sediment samples from Kazipally lake and Asanikunta tank, two Indian lakes with a history of severe pollution with fluoroquinolones, were investigated. Proportions of resistant bacteria were determined by selective cultivation, while horizontal gene transfer was studied using a GFP-tagged E. coli as recipient. Retrieved transconjugants were tested for susceptibility by Etest(®) and captured conjugative resistance elements were characterized by WGS. The polluted lakes harboured considerably higher proportions of ciprofloxacin-resistant and sulfamethoxazole-resistant bacteria than did other Indian and Swedish lakes included for comparison (52% versus 2% and 60% versus 7%, respectively). Resistance plasmids were captured from Kazipally lake, but not from any of the other lakes; in the case of Asanikunta tank because of high sediment toxicity. Eight unique IncA/C and IncN resistance plasmids were identified among 11 sequenced transconjugants. Five plasmids were fully assembled, and four of these carried the quinolone resistance gene qnrVC1, which has previously only been found on chromosomes. Acquired resistance genes, in the majority of cases associated with class 1 integrons, could be linked to decreased susceptibility to several different classes of antibiotics. Our study shows that environments heavily polluted with antibiotics contain novel multiresistance plasmids transferrable to E. coli. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Planar chromatography mediated screening of tetracycline and fluoroquinolone antibiotics in milk by fluorescence and mass selective detection.

    Science.gov (United States)

    Chen, Yisheng; Schwack, Wolfgang

    2013-10-18

    A rapid and efficient method for preliminary screening of four tetracyclines (tetracycline, chlortetracycline, oxytetracycline, doxycline) and three fluoroquinolones (enrofloxacin, ciprofloxacin, marbofloxacin), mostly detected in milk, by high-performance thin-layer chromatography-fluorescence detection and electrospray ionization mass spectrometry (HPTLC-FLD-ESI/MS) is highlighted. The optimized separation of the target antibiotics on ethylenediamine tetraacetic acid modified silica gel plates showed marked benefits for screening purposes. Besides, selective and sensitive densitometry in fluorescence mode was established with excitation at 366nm for the tetracyclines, 300nm for enrofloxacin and ciprofloxacin, and 280nm for marbofloxacin. Limits of detection (LOD) and quantitation (LOQ) with 95% confidence were in the range of 12-25 and 45-95μg/kg, respectively, in milk samples. Recoveries of target antibiotics from milk samples spiked at three critical levels (50, 100 and 150μg/kg) ranged from 76% to 105%. More importantly, a mass selective detection (MSD) was established as additional tool for confirmatory purposes. Using the elution-head based TLC-MS interface, the optimized elution flow consisting of acetonitrile/ammonium formate buffer (9/1, v/v) at a rate of 0.3mL/min enabled time-dependent resolution of analytes from the major interfering compounds, thus circumventing serious ion suppression effects. The established MSD assay also offered high sensitivity (25μg/kg) for confirmation, meeting Commission Regulation (EU) No. 37/2010. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Effects of light and microbial activity on the degradation of two fluoroquinolone antibiotics in pond water and sediment.

    Science.gov (United States)

    Lin, Juo-Shan; Pan, Hung-Yu; Liu, Shiu-Mei; Lai, Hong-Thih

    2010-07-01

    Enrofloxacin (ENR) and ciprofloxacin (CIP) are two fluoroquinolone (FQ) antibiotics widely used to treat diseases of human beings and cultured animals. These two FQs are usually detected in the effluent of municipal sewage plants and related aquatic environments. The purpose of this study was to understand the fates of ENR and CIP in aquaculture pond water and a sediment slurry in a laboratory-scale experiment. Effects of light and microbial activity on the degradation of these two FQs were investigated. Results indicated that natural irradiation plays a major role in the degradation of ENR and CIP in pond water and the sediment slurry. The 50 % dissipation times (DT(50)) with non-sterile treatment were 0.01 and 18.4 d for ENR, and 0.04 and 17.3 d for CIP in the water and sediment slurry, respectively. On the other hand, the degradation of ENR and CIP under dark conditions was slow or even hindered, and all of their DT(50) values exceeded 100 d. These two FQs degraded faster in the sediment slurry than in pond water under dark conditions. Artificial ultraviolet (UV) and fluorescence light had similar effects on the degradation of ENR in the pond water and sediment slurry. Degradation of CIP was faster with UV than with fluorescence light treatment, while no such difference was found for ENR degradation. CIP was a degradation product of ENR under both light and dark conditions, and DT(50) values for both compounds were shorter in the presence of light. The phenomenon of biodegradation was observed during degradation of CIP in the sediment slurry under natural light.

  17. Role of sulfate, chloride, and nitrate anions on the degradation of fluoroquinolone antibiotics by photoelectro-Fenton.

    Science.gov (United States)

    Villegas-Guzman, Paola; Hofer, Florian; Silva-Agredo, Javier; Torres-Palma, Ricardo A

    2017-12-01

    Taking ciprofloxacin (CIP) as a fluoroquinolone antibiotic model, this work explores the role of common anions (sulfate, nitrate, and chloride) during the application of photoelectro-Fenton (PEF) at natural pH to degrade this type of compound in water. The system was composed of an IrO 2 anode, Ti, or gas diffusion electrode (GDE) as cathode, Fe 2+ , and UV (254 nm). To determine the implications of these anions, the degradation pathway and efficiency of the PEF sub-processes (UV photolysis, anodic oxidation, and electro-Fenton at natural pH) were studied in the individual presence of the anions. The results highlight that degradation routes and kinetics are strongly dependent on electrolytes. When chloride and nitrate ions were present, indirect electro-chemical oxidation was identified by electro-generated HOCl and nitrogenated oxidative species, respectively. Additionally, direct photolysis and direct oxidation at the anode surface were identified as degradation routes. As a consequence of the different pathways, six primary CIP by-products were identified. Therefore, a scheme was proposed representing the pathways involved in the degradation of CIP when submitted to PEF in water with chloride, nitrate, and sulfate ions, showing the complexity of this process. Promoted by individual and synergistic actions of this process, the PEF system leads to a complete elimination of CIP with total removal of antibiotic activity against Staphylococcus aureus and Escherichia coli, and significant mineralization. Finally, the role of the anions was tested in seawater containing CIP, in which the positive contributions of the anions were partially suppressed by its OH radical scavenger action. The findings are of interest for the understanding of the degradation of antibiotics via the PEF process in different matrices containing sulfate, nitrate, and chloride ions.

  18. Development of a novel genetically modified bioluminescent-bacteria-based assay for detection of fluoroquinolones in animal-derived foods.

    Science.gov (United States)

    Cheng, Guyue; Dong, Xiaobing; Wang, Yulian; Peng, Dapeng; Wang, Xu; Hao, Haihong; Xie, Shuyu; Qu, Wei; Liu, Zhenli; Yuan, Zonghui

    2014-12-01

    Fluoroquinolones (FQNs) are broad-spectrum antibacterial agents widely used in animal husbandry and aquaculture. The residues and antimicrobial resistance of such antibiotics are a major public health concern. To realize multianalyte detection of FQN residues, a genetically modified bacterium, Escherichia coli pK12 harboring plasmid pRecAlux3, was constructed in this study to develop a bioluminescent-bacteria-based assay for the detection of FQNs in animal-derived foods. This assay was based on the principle of induction of an SOS response by FQNs via inducing the recA-promoter-fused luciferase reporter gene existing on the plasmid pRecAlux3. E. coli pK12 was able to recognize 11 FQNs: difloxacin, enrofloxacin, ciprofloxacin, sarafloxacin, norfloxacin, danofloxacin, ofloxacin, pefloxacin, lomefloxacin, marbofloxacin, and orbifloxacin. This method could be applied to 11 edible tissues, including milk, fish muscle, and the muscles, livers, and kidneys of cattle, chickens, and pigs, with a very simple and rapid sample extraction procedure using only phosphate-buffered saline. The limits of detection of the FQNs were between 12.5 and 100 μg kg(-1), all of which were lower than the maximum residue limits. Most of the recoveries of the FQNs were in the range from 60 to 120 %, and the interassay coefficients of variation were less than 30 %. This method, confirmed by high-performance liquid chromatography, is reliable and can be used as both a screening test and a semiquantitative assay, when the identity of a single type of FQN is known.

  19. Oxidation of fluoroquinolone antibiotics and structurally related amines by chlorine dioxide: Reaction kinetics, product and pathway evaluation.

    Science.gov (United States)

    Wang, Pei; He, Yi-Liang; Huang, Ching-Hua

    2010-12-01

    Fluoroquinolones (FQs) are a group of widely prescribed antibiotics and have been frequently detected in the aquatic environment. The reaction kinetics and transformation of seven FQs (ciprofloxacin (CIP), enrofloxacin (ENR), norfloxacin (NOR), ofloxacin (OFL), lomefloxacin (LOM), pipemidic acid (PIP) and flumequine (FLU)) and three structurally related amines (1-phenylpiperazine (PP), N-phenylmorpholine (PM) and 4-phenylpiperidine (PD)) toward chlorine dioxide (ClO(2)) were investigated to elucidate the behavior of FQs during ClO(2) disinfection processes. The reaction kinetics are highly pH-dependent, can be well described by a second-order kinetic model incorporating speciation of FQs, and follow the trend of OFL > ENR > CIP ∼ NOR ∼ LOM > > PIP in reactivity. Comparison among FQs and related amines and product characterization indicate that FQs' piperazine ring is the primary reactive center toward ClO(2). ClO(2) likely attacks FQ's piperazinyl N4 atom followed by concerted fragmentation involving piperazinyl N1 atom, leading to dealkylation, hydroxylation and intramolecular ring closure at the piperazine moiety. While FQs with tertiary N4 react faster with ClO(2) than FQs with secondary N4, the overall reactivity of the piperazine moiety also depends strongly on the quinolone ring through electronic effects. The reaction rate constants obtained in clean water matrix can be used to model the decay of CIP by ClO(2) in surface water samples, but overestimate the decay in wastewater samples. Overall, transformation of FQs, particularly for those with tertiary N4 amines, could be expected under typical ClO(2) disinfection conditions. However, the transformation may not eliminate antibacterial activity because of little destruction at the quinolone ring. Copyright © 2010 Elsevier Ltd. All rights reserved.

  20. Regional variations in fluoroquinolone non-susceptibility among Escherichia coli bloodstream infections within the Veterans Healthcare Administration

    Directory of Open Access Journals (Sweden)

    Daniel J. Livorsi

    2016-10-01

    Full Text Available Abstract Objectives We sought to define regional variations in fluoroquinolone non-susceptibility (FQ-NS among bloodstream isolates of Escherichia coli across the Veterans Health Administration (VHA in the United States. Methods We analyzed a retrospective cohort of patients managed at 136 VHA hospitals who had a blood culture positive for E.coli between 2003 and 2013. Hospitals were classified based on US Census Divisions, and regional variations in FQ-NS were analyzed. Results Twenty-four thousand five hundred twenty-three unique E.coli bloodstream infections (BSIs were identified between 2003 and 2013. 53.9 % of these were community-acquired, 30.7 % were healthcare-associated, and 15.4 % were hospital-onset BSIs. The proportion of E.coli BSIs with FQ-NS significantly varied across US Census Divisions (p < 0.001. During 2003–2013, the proportion of E.coli BSIs with FQ-NS was highest in the West South-Central Division (32.7 % and lowest in the Mountain Division (20.0 %. Multivariable analysis showed that there were universal secular trends towards higher FQ-NS rates (p < 0.001 with significant variability of slopes across US Census Divisions (p < 0.001. Conclusion There has been a universal increase in FQ-NS among E.coli BSIs within VHA, but the rate of increase has significantly varied across Census Divisions. The reasons for this variability are unclear. These findings reinforce the importance of using local data to develop and update local antibiograms and antibiotic-prescribing guidelines.

  1. [Ecology and fluoroquinolon resistance profiles in febrile urinary tract infections (FUTI) after prostate needle biopsy: A retrospective study in 466 biopsies].

    Science.gov (United States)

    Duboureau, H; Achkar, K; Stephan, R; Schmit, J L; Saint, F

    2017-05-01

    The biopsies of prostate are the reference examination to assert the diagnosis of prostate cancer. Even if the urinary infectious complications are rare thanks to the systematic oral antibiotic prophylaxis, they may still be serious. The SPILF (Society of Infectious Pathology and French language) published in 2014, an important increase of the resistances in fluoroquinolones for Escherichia coli (3 to 25%), whereas this is the most bacterium frequently found in the urinary infections (70-80%). The objectives of this study were to estimate the indicence of the febrile urinary tract infections after prostate needle biopsy and to define the ecology and the profile of E. coli's resistance. A total of 466 transrectal ultrasound-guided needle prostate biopsy were included in the study from 2012 to 2015. All the patients were taken care according to the recommendations of the AFU (Ouzzane et al., 2011). We estimated, for all the inclusive patients, if they had presented a clinic sign of urinary infection like fever or burning which suggestive of an urinary infection, and having a urines and blood culture, in the next 30 days the realization of the medical exam. Among 466 realized biopsies, seven patients developed a febril urinary tract infection (1.5%) [prostatitis (n=6), orchitis (n=1)]. Five infections to E. coli were identified; two were resistant for fluoroquinolones (40%). No germ was able to be identified for two patients. The infectious complications post-biopsy of prostate are rare (1.5%). E. coli is the germ most frequently identified with 40% of resistance with fluoroquinolones. 4. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  2. [The participation of the transport-barrier functions of the plasma membrane in the development of fluoroquinolone (ciprofloxacin) resistance in Acholeplasma laidlawii].

    Science.gov (United States)

    Abramycheva, N Iu; Govorun, V M

    2000-01-01

    The role of transport activity of Acholeplasma laidlawii plasmatic membrane in the development of resistance to ciprofloxacin was investigated. It was shown that ethidium bromide used as fluoroquinolone analogue in plasmatic membrane efflux pump was accumulated in ciprofloxacin-resistant cells in much less amount. It was estimated that ethidium bromide efflux depended on temperature, glucose and transmembrane electro-chemical proton potential. Inhibitors of efflux systems--reserpine and verapamil enhanced the ethidium bromide accumulation much more intensively in ciprofloxacin resistant cells. The results of investigation allowed to consider the existence of active efflux system for toxic agents in acholeplasma; in the case of ciprofloxacin-resistant strain these systems are inducible.

  3. Development of sensitive and reliable LC-MS/MS methods for the determination of three fluoroquinolones in water and fish tissue samples and preliminary environmental risk assessment of their presence in two rivers in northern Poland.

    Science.gov (United States)

    Wagil, Marta; Kumirska, Jolanta; Stolte, Stefan; Puckowski, Alan; Maszkowska, Joanna; Stepnowski, Piotr; Białk-Bielińska, Anna

    2014-09-15

    Antibiotic consumption (e.g. fluoroquinolones (FQs)) and, as a consequence, their presence in the environment, have received a lot of attention in the last several years due to increasing numbers of diseases and infections that are becoming resistant to traditional treatments for both humans and animals. In addition, even though antibiotics are safe for human and veterinary usage, ecosystems may be exposed to these substances. In this study, analytical methods for determining enrofloxacin (ENR), norfloxacin (NOR) and ciprofloxacin (CIP) in water samples and fish tissue based on the LC-MS/MS technique were developed and validated. As there is no data available concerning the risks posed by antibiotics in Poland, the proposed methods were applied for monitoring drug presence in environmental samples collected from two rivers in northern Poland. Evaluations of the ecotoxicity of ENR, NOR and CIP towards four different species of aquatic organisms: marine bacteria (Vibrio fischeri), green algae (Scenedesmus vacuolatus), duckweed (Lemna minor) and crustacean (Daphnia magna), were also carried out. All the investigated compounds were detected at least once in the survey. NOR was found to be the most ubiquitous drug with concentrations of up to 442.8 ng L(-1). Moreover, it was established that L. minor is the most sensitive species to the investigated drugs (EC50NOR = 0.13 mg L(-1), EC50ENR = 0.22 mg L(-1) and EC50CIP = 0.34 mg L(-1)). The calculated risk quotient (RQ) values confirmed that the concentrations of the investigated FQs in the environmental samples were at a level of moderate environmental risk (1environmental risk (RQCIP = 8.1). Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Surface interactions and degradation of a fluoroquinolone antibiotic in the dark in aqueous TiO{sub 2} suspensions

    Energy Technology Data Exchange (ETDEWEB)

    Peterson, Jonathan W., E-mail: peterson@hope.edu [Department of Geological & Environmental Sciences, Hope College, P.O. Box 9000, Holland, MI 49422-9000 (United States); Gu, Baohua [Environmental Sciences Division, Oak Ridge National Laboratory, P.O. Box 2008, Oak Ridge, TN 37831 (United States); Seymour, Michael D. [Department of Chemistry, Hope College, P.O. Box 9000, Holland, MI 49422-9000 (United States)

    2015-11-01

    Fluoroquinolone antibiotics (FQs) are important drugs used in human and veterinary medicine. Their detection in natural waters and waste water treatment plants, along with increased resistance to FQs among some bacteria, have generated an increased interest in the fate of these drugs in the environment. Partitioning of FQs between an aqueous solution and attendant substrates depends, in part, on the surface reactivity of the adsorbent, commonly a function of particle size, surface charge, and functional groups. This study investigated the surface interactions between the FQ drug ofloxacin (OFL) and titanium oxide (TiO{sub 2}), a common catalyst and widely-observed constituent in many consumer products. Raman and fluorescence spectroscopic techniques, as well as LC/MS, were used to determine the OFL moieties present on TiO{sub 2} surfaces and in attendant solutions. Raman spectra indicate that the C=O (ketone) group of the quinolone core, the NH{sup +} of the piperazinyl ring, and CH{sub 3} of benzoxazine core are the most active in sorption onto the TiO{sub 2} surface. Raman spectra also show that the sorbed benzoxazine–quinolone core and piperazinyl moieties are readily desorbed from the surface by re-suspending samples in water. Importantly, we found that OFL could be degraded by reacting with TiO{sub 2} even in the dark. Complementary LC/MS analysis of the attendant supernatants indicates the presence of de-piperazinylated and de-carboxylated OFL breakdown products in supernatant solutions. Together, both Raman and LC/MS analyses indicate that TiO{sub 2} breaks the compound into piperazinyl and carboxylate groups which attach to the surface, whereas de-carboxylated and hydroxylated quinolone moieties remain in solution. The present study thus identifies the sorption mechanisms and breakdown products of OFL during dark reactions with TiO{sub 2}, which is critically important for understanding the fate and transport of OFL as it enters the soil and aquatic

  5. Cytologic status changes of the conjunctiva and tears qualitative composition in patients with «dry eye» syndrome after instillation of modern topical fluoroquinolones

    Directory of Open Access Journals (Sweden)

    N. G. Zavgorodnyaya

    2014-06-01

    Full Text Available Aim. Use of the antibiotics for eye was approved as a rational method for reducing the risk of postoperative endophthalmitis. The aim of our investigation was to study the influence of the modern topical fluoroquinolones on the qualitative composition of tears and cytological status of the conjunctiva in patients with cataract and «dry eye» syndrome. Methods and results. 102 patients (109 eyes aged 36–87 years was examined. Qualitative composition of tear fluid was studied with method of native tears crystallography and conjunctiva cytological study using impression cytoscopy method. In 72.3% of cases the tears crystallography showed signs of pathology. Cytological examination of conjunctiva showed dystrophy in 86,8% of cases. In 11% of the patients typical cross-shaped crystals were detected. Conclusion. Correlation dependence analysis showed statistically significant positive relationship (Spearman’s correlation r=0.53 between the presence of cross-shaped crystals in crystallography and severe dystrophy of conjunctiva epithelium. Instillation of modern topical fluoroquinolones worsen the cytological status of conjunctiva epithelium.

  6. Phenotypic and Genotypic Efflux Pumps in Resistance to Fluoroquinolones in E.coli Isolated from Inpatients in Kermanshah Hospitals in 2013

    Directory of Open Access Journals (Sweden)

    Maryam Doosti Mohajer

    2017-12-01

    Full Text Available Abstract Background: Antibiotic resistance rates in E. coli are rapidly rising, especially with regard to fluoroquinolones. One of the mechanisms that lead to antibiotic resistance is efflux pumps. The aim of this study was phonotypic and genotypic analysis of efflux pump role in fluoroquinolones resistance of E. coli strains isolated from hospitalized patients in Kermanshah 2013. Materials and Methods: In this cross-sectional study, 100 isolates of E. coli were collected from hospitalized patients from Kermanshah. All isolates were identified by standard biochemical tests. The antimicrobial susceptibility patterns were determined by disk diffusion method according to CLSI guidelines. The presence of Efflux pump genes was determined by a PCR method. Results: The rates of resistance to Ceftazidime, Nalidixic Acid, Ciprofloxacin, Norfloxacin, Ofloxacin, Gentamicin, and Tetracycline were 73%, 67%, 55%, 54%, 45%, 38%, and 24%, respectively. According to the results of PCR test, of 100 E. coli isolates, 99% of isolates were positive for acrA, 98% for acrB, 95% for acrE, 98% for acrF, 94% for mdfA, 96% for norE, and 96% for tolC. Conclusion: In Strains with positive gene acrA, acrB, acrA, acrB, tolC, mdfA, norE, the presence of efflux pump inhibitor reduced the amount of resistance to antibiotics. So, efflux pumps are important in antibiotic resistance.

  7. Concentrated Ownership

    DEFF Research Database (Denmark)

    Rose, Caspar

    2014-01-01

    This entry summarizes the main theoretical contributions and empirical findings in relation to concentrated ownership from a law and economics perspective. The various forms of concentrated ownership are described as well as analyzed from the perspective of the legal protection of investors......, especially minority shareholders. Concentrated ownership is associated with benefits and costs. Concentrated ownership may reduce agency costs by increased monitoring of top management. However, concentrated ownership may also provide dominating owners with private benefits of control....

  8. Jejunal feeding is followed by a greater rise in plasma cholecystokinin, peptide YY, glucagon-like peptide 1, and glucagon-like peptide 2 concentrations compared with gastric feeding in vivo in humans

    NARCIS (Netherlands)

    Luttikhold, Joanna; Norren, Van Klaske; Rijna, Herman; Buijs, Nikki; Ankersmit, Marjolein; Heijboer, Annemieke C.; Gootjes, Jeannette; Hartmann, Bolette; Holst, Jens J.; Loon, Van Luc J.C.; Leeuwen, Van P.A.M.

    2016-01-01

    Background: Jejunal feeding is preferred instead of gastric feeding in patients who are intolerant to gastric feeding or at risk of aspiration. However, the impact of gastric feeding compared with that of jejunal feeding on postprandial circulating plasma glucose and amino acid concentrations and

  9. Jejunal feeding is followed by a greater rise in plasma cholecystokinin, peptide YY, glucagon-like peptide 1, and glucagon-like peptide 2 concentrations compared with gastric feeding in vivo in humans: a randomized trial

    NARCIS (Netherlands)

    Luttikhold, Joanna; van Norren, Klaske; Rijna, Herman; Buijs, Nikki; Ankersmit, Marjolein; Heijboer, Annemieke C.; Gootjes, Jeannette; Hartmann, Bolette; Holst, Jens J.; van Loon, Luc Jc; van Leeuwen, Paul Am

    2016-01-01

    Jejunal feeding is preferred instead of gastric feeding in patients who are intolerant to gastric feeding or at risk of aspiration. However, the impact of gastric feeding compared with that of jejunal feeding on postprandial circulating plasma glucose and amino acid concentrations and the associated

  10. In vivo evaluation of radiotracers targeting the melanin-concentrating hormone receptor 1: [11C]SNAP-7941 and [18F]FE@SNAP reveal specific uptake in the ventricular system.

    Science.gov (United States)

    Zeilinger, Markus; Dumanic, Monika; Pichler, Florian; Budinsky, Lubos; Wadsak, Wolfgang; Pallitsch, Katharina; Spreitzer, Helmut; Lanzenberger, Rupert; Hacker, Marcus; Mitterhauser, Markus; Philippe, Cécile

    2017-08-14

    The MCHR1 is involved in the regulation of energy homeostasis and changes of the expression are linked to a variety of associated diseases, such as diabetes and adiposity. The study aimed at the in vitro and in vivo evaluation of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP as potential PET-tracers for the MCHR1. Competitive binding studies with non-radioactive derivatives and small-animal PET/CT and MRI brain studies were performed under baseline conditions and tracer displacement with the unlabelled MCHR1 antagonist (±)-SNAP-7941. Binding studies evinced high binding affinity of the non-radioactive derivatives. Small-animal imaging of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP evinced high tracer uptake in MCHR1-rich regions of the ventricular system. Quantitative analysis depicted a significant tracer reduction after displacement with (±)-SNAP-7941. Due to the high binding affinity of the non-labelled derivatives and the high specific tracer uptake of [ 11 C]SNAP-7941 and [ 18 F]FE@SNAP, there is strong evidence that both radiotracers may serve as highly suitable agents for specific MCHR1 imaging.

  11. Elliptical concentrators.

    Science.gov (United States)

    Garcia-Botella, Angel; Fernandez-Balbuena, Antonio Alvarez; Bernabeu, Eusebio

    2006-10-10

    Nonimaging optics is a field devoted to the design of optical components for applications such as solar concentration or illumination. In this field, many different techniques have been used to produce optical devices, including the use of reflective and refractive components or inverse engineering techniques. However, many of these optical components are based on translational symmetries, rotational symmetries, or free-form surfaces. We study a new family of nonimaging concentrators called elliptical concentrators. This new family of concentrators provides new capabilities and can have different configurations, either homofocal or nonhomofocal. Translational and rotational concentrators can be considered as particular cases of elliptical concentrators.

  12. Human plasma concentrations of tolbutamide and acetaminophen extrapolated from in vivo animal pharmacokinetics using in vitro human hepatic clearances and simple physiologically based pharmacokinetic modeling for radio-labeled microdose clinical studies

    International Nuclear Information System (INIS)

    Yamazaki, Hiroshi; Kunikane, Eriko; Nishiyama, Sayako; Murayama, Norie; Shimizu, Makiko; Sugiyama, Yuichi; Chiba, Koji; Ikeda, Toshihiko

    2015-01-01

    The aim of the current study was to extrapolate the pharmacokinetics of drug substances orally administered in humans from rat pharmacokinetic data using tolbutamide and acetaminophen as model compounds. Adjusted animal biomonitoring equivalents from rat studies based on reported plasma concentrations were scaled to human biomonitoring equivalents using known species allometric scaling factors. In this extrapolation, in vitro metabolic clearance data were obtained using liver preparations. Rates of tolbutamide elimination were roughly similar in rat and human liver microsome experiments, but acetaminophen elimination by rat liver microsomes and cytosolic preparations showed a tendency to be faster than those in humans. Using a simple physiologically based pharmacokinetic (PBPK) model, estimated human plasma concentrations of tolbutamide and acetaminophen were consistent with reported concentrations. Tolbutamide cleared in a roughly similar manner in humans and rats, but medical-dose levels of acetaminophen cleared (dependent on liver metabolism) more slowly from plasma in humans than it did in rats. The data presented here illustrate how pharmacokinetic data in combination with a simple PBPK model can be used to assist evaluations of the pharmacological/toxicological potential of new drug substances and for estimating human radiation exposures from radio-labeled drugs when planning human studies. (author)

  13. Concentration risk

    Directory of Open Access Journals (Sweden)

    Matić Vesna

    2016-01-01

    Full Text Available Concentration risk has been gaining a special dimension in the contemporary financial and economic environment. Financial institutions are exposed to this risk mainly in the field of lending, mostly through their credit activities and concentration of credit portfolios. This refers to the concentration of different exposures within a single risk category (credit risk, market risk, operational risk, liquidity risk.

  14. In Vivo Transmission of an IncA/C Plasmid in Escherichia coli Depends on Tetracycline Concentration, and Acquisition of the Plasmid Results in a Variable Cost of Fitness.

    Science.gov (United States)

    Johnson, Timothy J; Singer, Randall S; Isaacson, Richard E; Danzeisen, Jessica L; Lang, Kevin; Kobluk, Kristi; Rivet, Bernadette; Borewicz, Klaudyna; Frye, Jonathan G; Englen, Mark; Anderson, Janet; Davies, Peter R

    2015-05-15

    IncA/C plasmids are broad-host-range plasmids enabling multidrug resistance that have emerged worldwide among bacterial pathogens of humans and animals. Although antibiotic usage is suspected to be a driving force in the emergence of such strains, few studies have examined the impact of different types of antibiotic administration on the selection of plasmid-containing multidrug resistant isolates. In this study, chlortetracycline treatment at different concentrations in pig feed was examined for its impact on selection and dissemination of an IncA/C plasmid introduced orally via a commensal Escherichia coli host. Continuous low-dose administration of chlortetracycline at 50 g per ton had no observable impact on the proportions of IncA/C plasmid-containing E. coli from pig feces over the course of 35 days. In contrast, high-dose administration of chlortetracycline at 350 g per ton significantly increased IncA/C plasmid-containing E. coli in pig feces (P IncA/C plasmid to other indigenous E. coli hosts. There was no evidence of conjugal transfer of the IncA/C plasmid to bacterial species other than E. coli. In vitro competition assays demonstrated that bacterial host background substantially impacted the cost of IncA/C plasmid carriage in E. coli and Salmonella. In vitro transfer and selection experiments demonstrated that tetracycline at 32 μg/ml was necessary to enhance IncA/C plasmid conjugative transfer, while subinhibitory concentrations of tetracycline in vitro strongly selected for IncA/C plasmid-containing E. coli. Together, these experiments improve our knowledge on the impact of differing concentrations of tetracycline on the selection of IncA/C-type plasmids. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Concentrator Photovoltaics

    CERN Document Server

    Luque, Antonio L

    2007-01-01

    Photovoltaic solar-energy conversion is one of the most promising technologies for generating renewable energy, and conversion of concentrated sunlight can lead to reduced cost for solar electricity. In fact, photovoltaic conversion of concentrated sunlight insures an efficient and cost-effective sustainable power resource. This book gives an overview of all components, e.g. cells, concentrators, modules and systems, for systems of concentrator photovoltaics. The authors report on significant results related to design, technology, and applications, and also cover the fundamental physics and market considerations. Specific contributions include: theory and practice of sunlight concentrators; an overview of concentrator PV activities; a description of concentrator solar cells; design and technology of modules and systems; manufacturing aspects; and a market study.

  16. In vivo 3D measurement of moxifloxacin and gatifloxacin distributions in the mouse cornea using multiphoton microscopy

    Science.gov (United States)

    Lee, Seunghun; Lee, Jun Ho; Park, Jin Hyoung; Yoon, Yeoreum; Chung, Wan Kyun; Tchah, Hungwon; Kim, Myoung Joon; Kim, Ki Hean

    2016-05-01

    Moxifloxacin and gatifloxacin are fourth-generation fluoroquinolone antibiotics used in the clinic to prevent or treat ocular infections. Their pharmacokinetics in the cornea is usually measured from extracted ocular fluids or tissues, and in vivo direct measurement is difficult. In this study multiphoton microscopy (MPM), which is a 3D optical microscopic technique based on multiphoton fluorescence, was applied to the measurement of moxifloxacin and gatifloxacin distribution in the cornea. Intrinsic multiphoton fluorescence properties of moxifloxacin and gatifloxacin were characterized, and their distributions in mouse cornea in vivo were measured by 3D MPM imaging. Both moxifloxacin and gatifloxacin had similar multiphoton spectra, while moxifloxacin had stronger fluorescence than gatifloxacin. MPM imaging of mouse cornea in vivo showed (1) moxifloxacin had good penetration through the superficial corneal epithelium, while gatifloxacin had relatively poor penetration, (2) both ophthalmic solutions had high intracellular distribution. In vivo MPM results were consistent with previous studies. This study demonstrates the feasibility of MPM as a method for in vivo direct measurement of moxifloxacin and gatifloxacin in the cornea.

  17. A multiplex single nucleotide polymorphism typing assay for detecting mutations that result in decreased fluoroquinolone susceptibility in Salmonella enterica serovars Typhi and Paratyphi A.

    LENUS (Irish Health Repository)

    Song, Yajun

    2010-08-01

    OBJECTIVES: Decreased susceptibility to fluoroquinolones has become a major problem for the successful therapy of human infections caused by Salmonella enterica, especially the life-threatening typhoid and paratyphoid fevers. METHODS: By using Luminex xTAG beads, we developed a rapid, reliable and cost-effective multiplexed genotyping assay for simultaneously detecting 11 mutations in gyrA, gyrB and parE of S. enterica serovars Typhi and Paratyphi A that result in nalidixic acid resistance (Nal(R)) and\\/or decreased susceptibility to fluoroquinolones. RESULTS: This assay yielded unambiguous single nucleotide polymorphism calls on extracted DNA from 292 isolates of Salmonella Typhi (Nal(R) = 223 and Nal(S) = 69) and 106 isolates of Salmonella Paratyphi A (Nal(R) = 24 and Nal(S) = 82). All of the 247 Nal(R) Salmonella Typhi and Salmonella Paratyphi A isolates were found to harbour at least one of the target mutations, with GyrA Phe-83 as the most common one (143\\/223 for Salmonella Typhi and 18\\/24 for Salmonella Paratyphi A). We also identified three GyrB mutations in eight Nal(S) Salmonella Typhi isolates (six for GyrB Phe-464, one for GyrB Leu-465 and one for GyrB Asp-466), and mutations GyrB Phe-464 and GyrB Asp-466 seem to be related to the decreased ciprofloxacin susceptibility phenotype in Salmonella Typhi. This assay can also be used directly on boiled single colonies. CONCLUSIONS: The assay presented here would be useful for clinical and reference laboratories to rapidly screen quinolone-resistant isolates of Salmonella Typhi and Salmonella Paratyphi A, and decipher the underlying genetic changes for epidemiological purposes.

  18. In vivo X-ray fluorescence analysis

    International Nuclear Information System (INIS)

    Ahlgren, L.

    1980-02-01

    Measurements on five occupationally exposed persons have shown that it is possible to use X-ray fluorescence analysis for in vivo measurements of lead in the skeleton. The technique for calibrating in vivo X-ray fluorescence measurements of lead in bone tissue has been studied in detail and a two-component phantom simulating the bone and the soft tissue parts of the finger constructed. The technique has been used for in vivo measurements on 22 occupationally exposed persons. The minimum detectable concentration of lead in fingerbones was found to be around 20 μg x g -1 . The lead concentrations in their skeletons and blood were compared: the correlation was poor. The variations in lead concentrations in the skeleton have been studied in occupationally exposed persons and in samples from archaeological skeletons. The sensitivity and the minimum detectable concentration of cadmium in the kidney cortex in in vivo measurements has been studied by measurements on kidney models. The minimum detectable concentration was 20 μg x g -1 at a skin-kidney distance of 30 mm and 40 μg x g -1 at 40 mm. Five persons occupationally exposed were studied. (Author)

  19. Concentrating Radioactivity

    Science.gov (United States)

    Herrmann, Richard A.

    1974-01-01

    By concentrating radioactivity contained on luminous dials, a teacher can make a high reading source for classroom experiments on radiation. The preparation of the source and its uses are described. (DT)

  20. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

    Science.gov (United States)

    Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

    2018-01-01

    Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo . © FASEB.

  1. Seasonal variation of antibiotics concentration in the aquatic environment: a case study at Jianghan Plain, central China.

    Science.gov (United States)

    Yao, Linlin; Wang, Yanxin; Tong, Lei; Li, Yonggang; Deng, Yamin; Guo, Wei; Gan, Yiqun

    2015-09-15

    25 antibiotics (macrolides, tetracyclines, fluoroquinolones and sulfonamides) were detected in swine wastewater, river water, rivulet water and in groundwater samples from multi-level monitoring boreholes (with sampling ports, respectively, at 10, 25 and 50 m below the land surface) at Jianghan Plain, central China. Except swine wastewater, the antibiotic concentrations in groundwater, river and rivulet water were higher in spring than those in winter. Nineteen antibiotics were detected at 100% frequencies in all kinds of water samples. In groundwater, fluoroquinolones and tetracyclines were the predominant antibiotics and the total concentrations of 25 antibiotics commonly decreased with the aquifer depth. Most groundwater samples collected in spring had high concentrations of norfloxacin, with average values of 65.27 ng · L(-1), 37.28 ng · L(-1) and 46.83 ng · L(-1), respectively, at 10, 25 and 50 m deep boreholes. By contrast, the concentrations of sulfamethazine and erythromycin were rather low in groundwater, but high in surface water. Groundwater samples collected from sites close to rivers or rivulets had much higher contents of antibiotics than those from other sites, indicating that the dominant source of antibiotics in groundwater should be the contaminated rivers or rivulets, rather than the scattered pig and poultry farms in the study area. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. The in vivo biofilm

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Alhede, Maria; Alhede, Morten

    2013-01-01

    Bacteria can grow and proliferate either as single, independent cells or organized in aggregates commonly referred to as biofilms. When bacteria succeed in forming a biofilm within the human host, the infection often becomes very resistant to treatment and can develop into a chronic state. Biofilms...... have been studied for decades using various in vitro models, but it remains debatable whether such in vitro biofilms actually resemble in vivo biofilms in chronic infections. In vivo biofilms share several structural characteristics that differ from most in vitro biofilms. Additionally, the in vivo...... experimental time span and presence of host defenses differ from chronic infections and the chemical microenvironment of both in vivo and in vitro biofilms is seldom taken into account. In this review, we discuss why the current in vitro models of biofilms might be limited for describing infectious biofilms...

  3. Prevalence and characteristics of extended-spectrum β-lactamase and plasmid-mediated fluoroquinolone resistance genes in Escherichia coli isolated from chickens in Anhui province, China.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available The aim of this study was to characterize the prevalence of extended-spectrum β-lactamase (ESBL genes and plasmid-mediated fluoroquinolone resistance (PMQR determinants in 202 Escherichia coli isolates from chickens in Anhui Province, China, and to determine whether ESBL and PMQR genes co-localized in the isolates. Antimicrobial susceptibility for 12 antimicrobials was determined by broth microdilution. Polymerase chain reactions (PCRs, DNA sequencing, and pulsed field gel electrophoresis (PFGE were employed to characterize the molecular basis for β-lactam and fluoroquinolone resistance. High rates of antimicrobial resistance were observed, 147 out of the 202 (72.8% isolates were resistant to at least 6 antimicrobial agents and 28 (13.9% of the isolates were resistant to at least 10 antimicrobials. The prevalence of blaCTX-M, blaTEM-1 and blaTEM-206 genes was 19.8%, 24.3% and 11.9%, respectively. Seventy-five out of the 202 (37.1% isolates possessed a plasmid-mediated quinolone resistance determinant in the form of qnrS (n = 21; this determinant occurred occasionally in combination with aac(6'-1b-cr (n = 65. Coexistence of ESBL and/or PMQR genes was identified in 31 of the isolates. Two E. coli isolates carried blaTEM-1, blaCTX-M and qnrS, while two others carried blaCTX-M, qnrS and aac(6'-1b-cr. In addition, blaTEM-1, qnrS and aac(6'-1b-cr were co-located in two other E. coli isolates. PFGE analysis showed that these isolates were not clonally related and were genetically diverse. To the best of our knowledge, this study is the first to describe detection of TEM-206-producing E. coli in farmed chickens, and the presence of blaTEM-206, qnrS and aac(6'-1b-cr in one of the isolates.

  4. High-level fluoroquinolone resistant Salmonella enterica serovar Kentucky ST198 epidemic clone with IncA/C conjugative plasmid carrying bla(CTX-M-25) gene.

    Science.gov (United States)

    Wasyl, Dariusz; Kern-Zdanowicz, Izabela; Domańska-Blicharz, Katarzyna; Zając, Magdalena; Hoszowski, Andrzej

    2015-01-30

    Multidrug resistant Salmonella Kentucky strains have been isolated from turkeys in Poland since 2009. Multiple mutations within chromosomal genes gyrA and parC were responsible for high-level ciprofloxacin resistance. One of the isolates was extended spectrum β-lactamase- (ESBL) positive: the strain 1643/2010 carried a conjugative 167,779 bps plasmid of IncA/C family. The sequence analysis revealed that it carried a blaCTX-M-25 gene and an integron with another β-lactamase encoding gene-blaOXA-21. This is the first known report of a CTX-M-25 encoding gene both in Poland and in Salmonella Kentucky world-wide, as well as in the IncA/C plasmid. Analysis of the integron showed a novel arrangement of gene cassettes-aacA4, aacC-A1 and blaOXA-21 where the latter might result from an intergeneric gene transfer. The study confirmed Salmonella Kentucky population isolated in Poland belongs to global epidemics of high level fluoroquinolone resistant clone ST198 that can carry rare β-lactamase genes. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Randomized clinical study for comparative evaluation of fourth-generation fluoroquinolones with the combination of fortified antibiotics in the treatment of bacterial corneal ulcers.

    Science.gov (United States)

    Shah, Vinit Mahendra; Tandon, Radhika; Satpathy, Gita; Nayak, Niranjan; Chawla, Bhavna; Agarwal, Tushar; Sharma, Namrata; Titiyal, Jeewan S; Vajpayee, Rasik B

    2010-07-01

    Comparative evaluation of efficacy of monotherapy with moxifloxacin (0.5%) or gatifloxacin (0.3%) with combination therapy of cefazolin (5%) and tobramycin (1.3%) in treatment of bacterial corneal ulcers. Patients diagnosed with bacterial keratitis (ulcer diameter 2-8 mm) were randomized to 1 of the 3 treatment groups (tobramycin 1.3% and cefazolin 5%, gatifloxacin 0.3%, or moxifloxacin 0.5%). After obtaining corneal scrapings, assigned study medication was instilled hourly for 48 hours and tapered as per clinical response. Healing of ulcer, duration to cure, adverse reactions, antibiogram profile, treatment failures, final visual acuity, and corneal opacity size were evaluated. A total of 61 patients were enrolled [cefazolin and tobramycin (n = 20), gatifloxacin (n = 21), and moxifloxacin (n = 20)]. Overall, 57 patients (93%) healed on treatment. On comparison of the mean time taken to heal, no statistically significant difference was found among all the 3 treatment groups (P = 0.98). Positive bacterial culture was obtained in only 38 patients (62%). There was no significant difference in the bacterial isolates in each treatment group. There were 4 (7%) treatment failures (perforation or nonhealing ulcer): 1 (5%) each in moxifloxacin and gatifloxacin group and 2 (10%) in fortified antibiotics group. All regimens were well tolerated. The study failed to find a difference in the efficacy of monotherapy with fourth-generation fluoroquinolones in the treatment of bacterial corneal ulcers of 2-8 mm size when compared with combination therapy of fortified antibiotics.

  6. Mass Spectrometric Study of Some Fluoroquinolone Drugs Using Electron Ionization and Chemical Ionization Techniques in Combination With Semi-Empirical Calculations

    International Nuclear Information System (INIS)

    Abd EL Kareem, M.S.M.

    2013-01-01

    A mass spectrometer of the type QMS (SSQ710) is used to record the electron ionization mass spectra of some 6-fluoroquinolones molecules, namely: Norfloxacin, Pefloxacin, Ciprofloxacin and Levofloxacin.While the chemical ionization mass spectra of these compounds are recorded using Thermo Finnigan TRACE DSQ GC/MS system.In EI mass spectra, the relative intensities for the molecular ions [M] +. of the studied compounds and the prominent fragment ions are reported and discussed. Furthermore, fragmentation patterns for the four compounds have been suggested and discussed and the most important fragmentation processes such as [M-CO 2 ] +. , [M-C 2 H 4 N] + and [M-CO 2 -C 2 H 4 N] + are investigated.On the other hand, the chemical ionization (CI) mass spectra of the compounds have been recorded using methane as the reagent gas. These spectra are discussed in terms of the structure of the compounds, with particular reference to their conventional electron ionization mass spectra. The protonated molecules [M + H] + are more relatively intense than [M] +. ions in the recorded EI mass spectra indicating higher stability in the case of [M + H] + .Also, fragmentation patterns for the four compounds have been suggested and discussed (using chemical ionization technique) and the most important fragmentation processes such as [MH-CO 2 ] +. , [MH-C 2 H 4 N] + and [MH-H 2 O] + are investigated.

  7. A new modeling strategy for third-order fast high-performance liquid chromatographic data with fluorescence detection. Quantitation of fluoroquinolones in water samples.

    Science.gov (United States)

    Alcaráz, Mirta R; Bortolato, Santiago A; Goicoechea, Héctor C; Olivieri, Alejandro C

    2015-03-01

    Matrix augmentation is regularly employed in extended multivariate curve resolution-alternating least-squares (MCR-ALS), as applied to analytical calibration based on second- and third-order data. However, this highly useful concept has almost no correspondence in parallel factor analysis (PARAFAC) of third-order data. In the present work, we propose a strategy to process third-order chromatographic data with matrix fluorescence detection, based on an Augmented PARAFAC model. The latter involves decomposition of a three-way data array augmented along the elution time mode with data for the calibration samples and for each of the test samples. A set of excitation-emission fluorescence matrices, measured at different chromatographic elution times for drinking water samples, containing three fluoroquinolones and uncalibrated interferences, were evaluated using this approach. Augmented PARAFAC exploits the second-order advantage, even in the presence of significant changes in chromatographic profiles from run to run. The obtained relative errors of prediction were ca. 10 % for ofloxacin, ciprofloxacin, and danofloxacin, with a significant enhancement in analytical figures of merit in comparison with previous reports. The results are compared with those furnished by MCR-ALS.

  8. Epidemiology and Characteristics of Escherichia coli Sequence Type 131 (ST131) from Long-Term Care Facility Residents Colonized Intestinally with Fluoroquinolone-Resistant Escherichia coli

    Science.gov (United States)

    Han, Jennifer H.; Garrigan, Charles; Johnston, Brian; Nachamkin, Irving; Clabots, Connie; Bilker, Warren B.; Santana, Evelyn; Tolomeo, Pam; Maslow, Joel; Myers, Janice; Carson, Lesley; Lautenbach, Ebbing; Johnson, James R.

    2016-01-01

    The objective of this study was to evaluate molecular and epidemiologic factors associated with Escherichia coli sequence type 131 (ST131) among long-term care facility (LTCF) residents who acquired gastrointestinal tract colonization with fluoroquinolone-resistant E. coli (FQREC). Colonizing isolates from 37 residents who newly developed FQREC colonization at three LTCFs from 2006–2008 were evaluated. Twenty-nine (78%) of 37 total FQREC colonizing isolates were ST131. Most ST131 isolates had a distinctive combination of gyrA and parC replacement mutations. The ST131 and non-ST131 isolates differed significantly for the prevalence of many individual virulence factors but not for the proportion that qualified molecularly as extraintestinal pathogenic E. coli (ExPEC) or aggregate virulence factor scores. E. coli ST131 was highly prevalent among LTCF residents with FQREC colonization. Future studies should determine the risk factors for infection among ST131-colonized residents, and assess the potential for increased transmissibility of ST131 in the long-term care setting. PMID:27939288

  9. [Proper use of fluoroquinolones in hospitalized elderly patients: Realisation of a clinical audit in geriatric hospitals of Lyon University Hospital].

    Science.gov (United States)

    Papailhau, C; Gaujard, S; Girard, R; Bourguignon, L; Mouchoux, C

    2018-05-18

    Fluoroquinolones (FQ) are widely used because of their broad spectrum and their ease of use, especially in the elderly. Nevertheless, their misuse is behind the development and the emergence of bacterial resistances. The objective of this study was to evaluate the compliance of FQ prescriptions in the elderly hospitalized, before and after pharmaceutical interventions (PI). A prospective clinical audit was conducted for three months in three geriatric hospitals. A pharmacist carried out the evaluation of the prescription's conformity with the help of referent geriatric doctor in infectiology according to the criteria defined by SPILF recommendations (2015). The PIs and their future have been collected and codified. A total of 100 patients were included (mean age: 85.3 years; male female ratio: 1,17). The medical-pharmaceutical collaboration helped to increase the overall compliance rate from 56 to 80%. FQ were used for urinary (72%) or respiratory (20%) infections, first-line (57%), documented (60%) and monotherapy (63%). Our results show that FQ misuse is a not inconsiderable case since in 28% they should not have been prescribed. Thirty-three PI were performed and accepted in 72% cases. Actions to promote the FQ proper use have therefore been put in place: communication of the audit results, dissemination of a summary of SPILF recommendations and creation of a tool to assist in the analysis of prescriptions FQ for pharmacists. Copyright © 2018. Published by Elsevier SAS.

  10. Desmosomes In Vivo

    Directory of Open Access Journals (Sweden)

    David Garrod

    2010-01-01

    Full Text Available The structure, function, and regulation of desmosomal adhesion in vivo are discussed. Most desmosomes in tissues exhibit calcium-independent adhesion, which is strongly adhesive or “hyperadhesive”. This is fundamental to tissue strength. Almost all studies in culture are done on weakly adhesive, calcium-dependent desmosomes, although hyperadhesion can be readily obtained in confluent cell culture. Calcium dependence is a default condition in vivo, found in wounds and embryonic development. Hyperadhesion appears to be associated with an ordered arrangement of the extracellular domains of the desmosomal cadherins, which gives rise to the intercellular midline identified in ultrastructural studies. This in turn probably depends on molecular order in the desmosomal plaque. Protein kinase C downregulates hyperadhesion and there is preliminary evidence that it may also be regulated by tyrosine kinases. Downregulation of desmosomes in vivo may occur by internalisation of whole desmosomes rather than disassembly. Hyperadhesion has implications for diseases such as pemphigus.

  11. In vivo studies of opiate receptors

    International Nuclear Information System (INIS)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented

  12. In vivo studies of opiate receptors

    Energy Technology Data Exchange (ETDEWEB)

    Frost, J.J.; Dannals, R.F.; Duelfer, T.; Burns, H.D.; Ravert, H.T.; Langstroem, B.; Balasubramanian, V.; Wagner, H.N. Jr.

    1984-01-01

    To study opiate receptors noninvasively in vivo using positron emission tomography, techniques for preferentially labeling opiate receptors in vivo can be used. The rate at which receptor-bound ligand clears from the brain in vivo can be predicted by measuring the equilibrium dissociation constant (KD) at 37 degrees C in the presence of 100 mM sodium chloride and 100 microM guanyl-5'-imidodiphosphate, the drug distribution coefficient, and the molecular weight. A suitable ligand for labeling opiate receptors in vivo is diprenorphine, which binds to mu, delta, and kappa receptors with approximately equal affinity in vitro. However, in vivo diprenorphine may bind predominantly to one opiate receptor subtype, possibly the mu receptor. To predict the affinity for binding to the opiate receptor, a Hansch correlation was determined between the 50% inhibitory concentration for a series of halogen-substituted fentanyl analogs and electronic, lipophilic, and steric parameters. Radiochemical methods for the synthesis of carbon-11-labeled diprenorphine and lofentanil are presented.

  13. Pharmaceutical applications of in vivo EPR

    International Nuclear Information System (INIS)

    Maeder, K.

    1998-01-01

    The aim of this article is to discuss the applications of in vivo EPR in the field of pharmacy. In addition to direct detection of free radical metabolites and measurement of oxygen, EPR can be used to characterize the mechanisms of drug release from biodegradable polymers. Unique information about drug concentration, the microenvironment (viscosity, polarity, pH) and biodistribution (by localized measurement or EPR Imaging) can be obtained. (author)

  14. - In vivo monitoring of 5-FU

    OpenAIRE

    Lucas, Susanne

    2010-01-01

    The aim of the present study was to establish the in vivo-monitoring of the enrichment of 5-FU liposomes in liver and liver metastases by MRI methods. Relative signal intensities of liver and tumor tissue were determined. After sacrifying animals concentrations of 5-FU and it´s active intracellular metabolite M3 were measured by HPLC techniques. We used CC531 adenocarcinoma in the liver of WAG/Rij rats as a standardized liver tumor model in our investigatio...

  15. Preparation of silica-supported carbon by Kraft lignin pyrolysis, and its use in solid-phase extraction of fluoroquinolones from environmental waters

    International Nuclear Information System (INIS)

    Speltini, Andrea; Sturini, Michela; Maraschi, Federica; Mandelli, Elettra; Dondi, Daniele; Profumo, Antonella; Vadivel, Dhanalakshmi

    2016-01-01

    The article describes a carbon-based material for solid-phase extraction (SPE) of fluoroquinolones from waters. It was obtained by pyrolytic deposition of Kraft lignin (LG) on silica particles. Marbofloxacin (MAR) and enrofloxacin (ENR) were chosen as model contaminants. The material was prepared by first adsorbing LG onto silica microparticles, this followed by pyrolytic treatment at 1200 °C for 2 h. Silica-supported carbon was characterized by scanning electron microscopy, surface area measurement (by BET), thermogravimetric analysis, and electron paramagnetic resonance. The carbon-coated silica particles were then tested as a column packing for SPE of MAR and ENR from spiked tap and river waters. Quantitative adsorption was observed at pH values of ∼7.5 for both drugs. They were eluted with a 70:30 mixture of aqueous tetrabutylammonium hydroxide and acetonitrile and then quantified by HPLC coupled to fluorescence detection. Samples spiked with MAR and ENR in the range from 10 to 1000 ng·L"−"1 gave recoveries ranging from 70 to 116% (for n = 3). Good inter-day precision (with RSDs between 7 and 16%) was observed for 20–1000 ng·L"−"1 spikes, also in natural river water. Sample volumes up to 500 mL provided enrichment factors up to 125, and this makes this material useful for determination of the two drugs at environmentally significant levels which are as low as a few ng·L"−"1. The batch-to-batch reproducibility was verified for 3 preparations. The sorbent was successfully applied to the determination of these drugs in environmental waters. (author)

  16. Trial Comparing a Combined Regimen of Amikacin and Ciprofloxacin to Ciprofloxacin Alone as Transrectal Prostate Biopsy Prophylaxis in the Era of High Fluoroquinolone-Resistant Rectal Flora.

    Science.gov (United States)

    Son, Kyung Chul; Chung, Ho Seok; Jung, Seung Il; Kim, Myung Soo; Hwang, Eu Chang; Kim, Jin Woong; Kwon, Dong Deuk

    2018-04-09

    To investigate whether addition of amikacin to fluoroquinolone (FQ) antimicrobial prophylaxis reduces infections after transrectal ultrasound-guided prostate biopsy (TRUSPB). A total of 503 patients undergoing rectal swab were divided into three groups. Patients with FQ-sensitive rectal flora (group 1, n = 248) were administered ciprofloxacin before TRUSPB, and patients with FQ-resistant rectal flora were either administered ciprofloxacin (group 2, n = 97) or amikacin and ciprofloxacin (group 3, n = 158) before TRUSPB. Based on the rectal swab, FQ resistance was 54.9%, and extended-spectrum β-lactamase (ESBL) positivity was 17.2%. The incidence of infectious complication in group 1 was 1.6%. Groups 2 and 3, with FQ-resistant rectal flora, tended to have increased infectious complications (5.2% and 4.4%, respectively) but the difference between those results is not statistically significant. The most common pathogens of infectious complications in patients with FQ-resistant rectal flora were FQ-resistant and ESBL-producing Escherichia coli. E. coli pathogens isolated in Group 3 were amikacin-susceptible species. The operation history and ESBL positivity of rectal flora increased the incidence of infectious complications (odds ratio [OR] = 3.68; P = 0.035 and OR = 4.02; P = 0.008, respectively). DM and antibiotics exposure were risk factors for FQ resistance (OR = 2.19; P = 0.002) and ESBL positivity of rectal flora (OR = 2.96; P = 0.005), respectively. Addition of amikacin to ciprofloxacin prophylaxis could not reduce infectious complications in patients with FQ-resistant rectal flora. Despite the amikacin sensitivity of infectious complications, single-dose amikacin addition to ciprofloxacin prophylaxis has limitations. © 2018 The Korean Academy of Medical Sciences.

  17. Risk Factors for the Development of Gastrointestinal Colonization With Fluoroquinolone-Resistant Escherichia coli in Residents of Long-Term Care Facilities

    Science.gov (United States)

    Han, Jennifer H.; Maslow, Joel; Han, Xiaoyan; Xie, Sharon X.; Tolomeo, Pam; Santana, Evelyn; Carson, Lesley; Lautenbach, Ebbing

    2014-01-01

    Background. The objective of this study was to assess risk factors for the development of fluoroquinolone (FQ)–resistant Escherichia coli gastrointestinal tract colonization in long-term care facility (LTCF) residents. Methods. A prospective cohort study was conducted from 2006 to 2008 at 3 LTCFs. Residents initially colonized with FQ-susceptible E. coli were followed by means of serial fecal sampling for new FQ-resistant E. coli colonization for up to 12 months or until discharge or death. A Cox proportional hazards regression model was developed to identify risk factors for new FQ-resistant E. coli colonization, with antibiotic and device exposures modeled as time-varying covariates. Results. Fifty-seven (47.5%) of 120 residents became newly colonized with FQ-resistant E. coli, with a median time to colonization of 57 days. Fecal incontinence (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.04–3.06; P = .04) was significantly associated with FQ-resistant E. coli acquisition. Receipt of amoxicillin-clavulanate (HR, 6.48; 95% CI, 1.43–29.4; P = .02) and the presence of a urinary catheter (HR, 3.81; 95% CI, 1.06–13.8; P = .04) during LTCF stay increased the risk of new FQ-resistant E. coli colonization. Conclusions. Acquisition of FQ-resistant E. coli was common, with nearly half of LTCF residents developing new FQ-resistant E. coli colonization. Further studies are needed on interventions to limit the emergence of FQ-resistant E. coli in LTCFs. PMID:23986544

  18. Antibiotics in riverine runoff of the Pearl River Delta and Pearl River Estuary, China: Concentrations, mass loading and ecological risks

    International Nuclear Information System (INIS)

    Xu, Weihai; Yan, Wen; Li, Xiangdong; Zou, Yongde; Chen, Xiaoxiang; Huang, Weixia; Miao, Li; Zhang, Ruijie; Zhang, Gan; Zou, Shichun

    2013-01-01

    Ten antibiotics belonging to three groups (macrolides, fluoroquinolones and sulfonamides) were investigated in riverine runoff of the Pearl River Delta (PRD) and Pearl River Estuary (PRE), South China for assessing the importance of riverine runoff in the transportation of contaminants from terrestrial sources to the open ocean. All antibiotics were detected in the eight outlets with concentrations ranging from 0.7 to 127 ng L −1 . The annual mass loadings of antibiotics from the PRD to the PRE and coast were 193 tons with 102 tons from the fluoroquinolone group. It showed that antibiotics decreased from the riverine outlets to the PRE and open ocean. Risk assessment showed that most of these antibiotics showed various ecological risks to the relevant aquatic organisms, in which ofloxacin (OFL), erythromycin (ETM) and ciprofloxacin (CIP) posed high ecological risks to the studied aquatic environments. -- Highlights: •Antibiotics were ubiquitous in the river water and costal water in the Pearl River Delta. •Antibiotics exhibited distinct temporal and spatial trends in the riverine runoff outlets. •Annual outflows of antibiotics were 193 tons from the Pearl River to coastal ocean. •Some antibiotics posed high risks to some organisms in the PRD environments. -- Antibiotics were ubiquitous in the river and coastal water in the Pearl River Delta and posed various ecological risks to the relevant aquatic organisms

  19. Dual Inhibition of Topoisomerase II and Tyrosine Kinases by the Novel Bis-Fluoroquinolone Chalcone-Like Derivative HMNE3 in Human Pancreatic Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Yong-Chao Ma

    Full Text Available Both tyrosine kinase and topoisomerase II (TopII are important anticancer targets, and their respective inhibitors are widely used in cancer therapy. However, some combinations of anticancer drugs could exhibit mutually antagonistic actions and drug resistance, which further limit their therapeutic efficacy. Here, we report that HMNE3, a novel bis-fluoroquinolone chalcone-like derivative that targets both tyrosine kinase and TopII, induces tumor cell proliferation and growth inhibition. The viabilities of 6 different cancer cell lines treated with a range of HMNE3 doses were detected using the 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay. Cellular apoptosis was determined using Hoechst 33258 fluorescence staining and the terminal deoxynucleotidyl transferase (TdT dUTP nick-end labeling (TUNEL assay. The expression of activated Caspase-3 was examined by immunocytochemistry. The tyrosine kinase activity was measured with a human receptor tyrosine kinase (RTK detection kit using a horseradish peroxidase (HRP-conjugated phosphotyrosine (pY20 antibody as the substrate. The topoisomerase II activity was measured using agarose gel electrophoresis with the DNA plasmid pBR322 as the substrate. The expression levels of the P53, Bax, Bcl-2, Caspase-3, -8, -9, p-cSrc, c-Src and topoisomerase II proteins were detected by western blot analysis. The proliferation of five of the six cancer cell lines was significantly inhibited by HMNE3 at 0.312 to 10 μmol/L in a time- and dose-dependent manner. Treatment of the Capan-1 and Panc-1 cells with 1.6 to 3.2 μM HMNE3 for 48 h significantly increased the percentage of apoptotic cells (P<0.05, and this effect was accompanied by a decrease in tyrosine kinase activity. HMNE3 potentially inhibited tyrosine kinase activity in vitro with an IC50 value of 0.64±0.34 μmol/L in Capan-1 cells and 3.1±0.86 μmol/L in Panc-1 cells. The activity of c-Src was significantly inhibited by HMNE3 in a dose

  20. Cadmium analysis in vivo

    International Nuclear Information System (INIS)

    Bergman, R.

    1980-12-01

    The report describes the development of a method for in vivo Cd-analysis. The method is based on the analysis of the prompt gamma radiation which is emitted by neutron capture of the isotope Cd113. Different parts of the body can be analysed selectively by neutrons in the interval of 1 to 100 KeV. The results show that the level of Cd in Kidneys can be measured without exceeding the dose of 40 mrad and that only 20% uncertainty is introduced when analysing Cd. The development has been made at the R2 reactor in Studsvik using 25 KeV neutrons. (G.B.)

  1. In vivo gluten challenge in coeliac disease

    Directory of Open Access Journals (Sweden)

    HJ Ellis

    2001-01-01

    Full Text Available In vivo gluten challenge has been used since the early 1950s to study the role of cereal fractions in celiac disease. While early studies relied on crude indicators of celiac toxicity, the advent of jejunal biopsy and sophisticated immunohistochemical techniques has allowed accurate studies to be performed. Studies to determine the nature of the cereal component that is toxic to patients with celiac disease have concentrated on wheat because of its nutritional importance. A number of in vitro studies indicated the presence of one or more celiac-activating epitopes with the N-terminus of the A-gliadin molecule. In vivo challenge with three synthetic peptides subsequently indicated the toxicity of a peptide corresponding to amino acids 31 to 49 of A-gliadin. In vivo gluten challenge is the gold standard for the assessment of celiac toxicity; however, jejunal biopsy is a relatively invasive procedure, thus, other methods have been investigated. Direct infusion of the rectum with gluten has been shown to result in an increase in mucosal intraepithelial lymphocytes, occurring only in celiac patients. This method has been used to study the celiac toxicity of gliadin subfractions. The in vitro technique of small intestinal biopsy organ culture is also a useful tool and appears to give the same results as in vivo challenge. The importance of tiny amounts of gliadin in the diet, such as that which occurs in wheat starch, has been studied by in vivo challenge; this technique has clarified the position of oats in the gluten-free diet. Several studies suggest that this cereal may be included in the diet of most adult celiac patients. Studies of the transport of gliadin across the enterocyte following ingestion or challenge suggest that gliadin may be metabolized by a different pathway in celiac disease. This could result in an abnormal presentation to the immune system, triggering a pathogenic rather than a tolerogenic response.

  2. EDITORIAL: Nanotechnology in vivo Nanotechnology in vivo

    Science.gov (United States)

    Demming, Anna

    2010-04-01

    -imaging labels [4]. A surface hydroxyl group renders silicon quantum dots soluble in water and the photoluminescence can be made stable with oxygen-passivation. In addition, researchers in Japan have demonstrated how the initially modest yield in the preparation of silicon quantum dots can be improved to tens of milligrams per batch, thus further promoting their application in bio-imaging [5]. In the search for non-toxic quantum dots, researchers at the Amrita Centre for Nanoscience in India have prepared heavy metal-free quantum dot bio-probes based on single phase ZnS [6]. The quantum dots are selectively doped with metals, transition metals and halides to provide tuneable luminescence properties, and they are surface conjugated with folic acid for cancer targeting. The quantum dots were demonstrated to be water-soluble, non-toxic in normal and cancer cell lines, and have bright, tuneable luminescence. So far most of the quantum dots developed for bio-imaging have had excitation and emission wavelengths in the visible spectrum, which is highly absorbed by tissue. This limits imaging with these quantum dots to superficial tissues. This week, researchers in China and the US reported work developing functionalized dots for in vivo tumour vasculature in the infrared part of the spectrum [7]. In addition the quantum dots were functionalised with glycine-aspartic acid (RGD) peptides, which target the vasculature of almost all types of growing tumours, unlike antibody- or aptamer-mediated targeting strategies that are specific to a particular cancer type. In this issue, researchers in China and the US demonstrate a novel type of contrast agent for ultrasonic tumour imaging [8]. Contrast-enhanced ultrasonic tumour imaging extends the diagnostic and imaging capabilities of traditional techniques. The use of nanoparticles as ultrasound contrast agents exploits the presence of open pores in the range of 380 to 780 nm in tumour blood vessels, which enhance the permeability and retention

  3. Using exomarkers to assess mitochondrial reactive species in vivo.

    Science.gov (United States)

    Logan, Angela; Cochemé, Helena M; Li Pun, Pamela Boon; Apostolova, Nadezda; Smith, Robin A J; Larsen, Lesley; Larsen, David S; James, Andrew M; Fearnley, Ian M; Rogatti, Sebastian; Prime, Tracy A; Finichiu, Peter G; Dare, Anna; Chouchani, Edward T; Pell, Victoria R; Methner, Carmen; Quin, Caroline; McQuaker, Stephen J; Krieg, Thomas; Hartley, Richard C; Murphy, Michael P

    2014-02-01

    The ability to measure the concentrations of small damaging and signalling molecules such as reactive oxygen species (ROS) in vivo is essential to understanding their biological roles. While a range of methods can be applied to in vitro systems, measuring the levels and relative changes in reactive species in vivo is challenging. One approach towards achieving this goal is the use of exomarkers. In this, exogenous probe compounds are administered to the intact organism and are then transformed by the reactive molecules in vivo to produce a diagnostic exomarker. The exomarker and the precursor probe can be analysed ex vivo to infer the identity and amounts of the reactive species present in vivo. This is akin to the measurement of biomarkers produced by the interaction of reactive species with endogenous biomolecules. Our laboratories have developed mitochondria-targeted probes that generate exomarkers that can be analysed ex vivo by mass spectrometry to assess levels of reactive species within mitochondria in vivo. We have used one of these compounds, MitoB, to infer the levels of mitochondrial hydrogen peroxide within flies and mice. Here we describe the development of MitoB and expand on this example to discuss how better probes and exomarkers can be developed. This article is part of a Special Issue entitled Current methods to study reactive oxygen species - pros and cons and biophysics of membrane proteins. Guest Editor: Christine Winterbourn. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

  4. Gut proteases target Yersinia invasin in vivo

    Directory of Open Access Journals (Sweden)

    Freund Sandra

    2011-04-01

    Full Text Available Abstract Background Yersinia enterocolitica is a common cause of food borne gastrointestinal disease. After oral uptake, yersiniae invade Peyer's patches of the distal ileum. This is accomplished by the binding of the Yersinia invasin to β1 integrins on the apical surface of M cells which overlie follicle associated lymphoid tissue. The gut represents a barrier that severely limits yersiniae from reaching deeper tissues such as Peyer's patches. We wondered if gut protease attack on invasion factors could contribute to the low number of yersiniae invading Peyer's patches. Findings Here we show that invasin is rapidly degraded in vivo by gut proteases in the mouse infection model. In vivo proteolytic degradation is due to proteolysis by several gut proteases such as trypsin, α-chymotrypsin, pancreatic elastase, and pepsin. Protease treated yersiniae are shown to be less invasive in a cell culture model. YadA, another surface adhesin is cleaved by similar concentrations of gut proteases but Myf was not cleaved, showing that not all surface proteins are equally susceptible to degradation by gut proteases. Conclusions We demonstrate that gut proteases target important Yersinia virulence factors such as invasin and YadA in vivo. Since invasin is completely degraded within 2-3 h after reaching the small intestine of mice, it is no longer available to mediate invasion of Peyer's patches.

  5. Sex differences in the pro-inflammatory cytokine response to endotoxin unfold in vivo but not ex vivo in healthy humans.

    Science.gov (United States)

    Wegner, Alexander; Benson, Sven; Rebernik, Laura; Spreitzer, Ingo; Jäger, Marcus; Schedlowski, Manfred; Elsenbruch, Sigrid; Engler, Harald

    2017-07-01

    Clinical data indicate that inflammatory responses differ across sexes, but the mechanisms remain elusive. Herein, we assessed in vivo and ex vivo cytokine responses to bacterial endotoxin in healthy men and women to elucidate the role of systemic and cellular factors underlying sex differences in inflammatory responses. Participants received an i.v. injection of low-dose endotoxin (0.4 ng/kg body mass), and plasma TNF-α and IL-6 responses were analyzed over a period of 6 h. In parallel, ex vivo cytokine production was measured in endotoxin-stimulated blood samples obtained immediately before in vivo endotoxin administration. As glucocorticoids (GCs) play an important role in the negative feedback regulation of the inflammatory response, we additionally analyzed plasma cortisol concentrations and ex vivo GC sensitivity of cytokine production. Results revealed greater in vivo pro-inflammatory responses in women compared with men, with significantly higher increases in plasma TNF-α and IL-6 concentrations. In addition, the endotoxin-induced rise in plasma cortisol was more pronounced in women. In contrast, no sex differences in ex vivo cytokine production and GC sensitivity were observed. Together, these findings demonstrate major differences in in vivo and ex vivo responses to endotoxin and underscore the importance of systemic factors underlying sex differences in the inflammatory response.

  6. Noninvasive in vivo oximetric imaging by radiofrequency FT EPR

    NARCIS (Netherlands)

    Subramanian, S; Yamada, K; Irie, A; Murugesan, R; Cook, JA; Devasahayam, N; Van Dam, GM; Mitchell, JB; Krishna, MC

    A novel method, called relaxo-oximetry, for rapid spatially resolved in vivo measurements of oxygen concentration using time-domain radiofrequency (RF) electron paramagnetic resonance (EPR) is described. Time-domain data from triaryl methyl (TAM)-based single-electron contrast agents were processed

  7. In Vivo Cytogenetic Studies on Aspartame

    Directory of Open Access Journals (Sweden)

    Entissar S. AlSuhaibani

    2010-01-01

    Full Text Available Aspartame (a-Laspartyl-L-phenylalanine 1-methylester is a dipeptide low-calorie artificial sweetener that is widely used as a nonnutritive sweetener in foods and drinks. The safety of aspartame and its metabolic breakdown products (phenylalanine, aspartic acid and methanol was investigated in vivo using chromosomal aberration (CA test and sister chromatid exchange (SCE test in the bone marrow cells of mice. Swiss Albino male mice were exposed to aspartame (3.5, 35, 350 mg/kg body weight. Bone marrow cells isolated from femora were analyzed for chromosome aberrations and sister chromatid exchanges. Treatment with aspartame induced dose dependently chromosome aberrations at all concentrations while it did not induce sister chromatid exchanges. On the other hand, aspartame did not decrease the mitotic index (MI. However, statistical analysis of the results show that aspartame is not significantly genotoxic at low concentration.

  8. Radon and its daughters in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Rundo, J

    1984-05-01

    Prolonged exposure to radon should build up a reservoir of radon in body fat and fluids. If the subject moved to an environment with a lower radon concentration from an environment with a higher level of radon, the result would be an exhalation of radon, and the initial exhalation rate of radon should depend of the radon concentration inhaled. This paper describes the behavior of radon and its daughters in vivo and a relationship between the radon exhalation rate and the time after a meal. A major but short-lived postprandial increase in the exhalation rate of radon was observed. The author reports a similar effect in the exhalation rate of radon by persons containing no radium. It should be noted that the possibility exists that a large amount of radon daughters in the chest may interfere in the investigation of possible internal contamination with plutonium or other actinides by external counting. 8 figures.

  9. Radon and its daughters in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Rundo, J

    1984-05-01

    Prolonged exposure to radon should build up a reservoir of radon in body fat and fluids. Movement of the subject to an environment with a lower radon concentration from an environment with a higher level of radon would result in an exhalation of radon, and the initial exhalation rate of radon should depend on the radon concentration inhaled. This paper describes the behavior of radon and its daughters in vivo and a relationship between the radon exhalation rate and the time after a meal. A major but short-lived postprandial increase in the exhalation rate of radon was observed. We report a similar effect in the exhalation rate of radon by persons containing no radium. It should be noted that the possibility exists that a large amount of radon daughters in the chest may interfere in the investigation of possible internal contamination with plutonium or other actinides by external counting. (author).

  10. Evaluation of the In Vivo and Ex Vivo Binding of Novel BC1 Cannabinoid Receptor Radiotracers

    Energy Technology Data Exchange (ETDEWEB)

    Miller, A.; Gatley, J.; Gifford, A.

    2002-01-01

    The primary active ingredient of marijuana, 9-tetrahydrocannabinol, exerts its psychoactive effects by binding to cannabinoid CB1 receptors. These receptors are found throughout the brain with high concentrations in the hippocampus and cerebellum. The current study was conducted to evaluate the binding of a newly developed putative cannabinoid antagonist, AM630, and a classical cannabinoid 8-tetrahydrocannabinol as potential PET and/or SPECT imaging agents for brain CB1 receptors. For both of these ligands in vivo and ex vivo studies in mice were conducted. AM630 showed good overall brain uptake (as measure by %IA/g) and a moderately rapid clearance from the brain with a half-clearance time of approximately 30 minutes. However, AM630 did not show selective binding to CB1 cannabinoid receptors. Ex vivo autoradiography supported the lack of selective binding seen in the in vivo study. Similar to AM630, 8-tetrahydrocanibol also failed to show selective binding to CB1 receptor rich brain areas. The 8-tetrahydrocanibol showed moderate overall brain uptake and relatively slow brain clearance as compared to AM630. Further studies were done with AM2233, a cannabinoid ligand with a similar structure as AM630. These studies were done to develop an ex vivo binding assay to quantify the displacement of [131I]AM2233 binding by other ligands in Swiss-Webster and CB1 receptor knockout mice. By developing this assay we hoped to determine the identity of an unknown binding site for AM2233 present in the hippocampus of CB1 knockout mice. Using an approach based on incubation of brain slices prepared from mice given intravenous [131I]AM2233 in either the presence or absence of AM2233 (unlabelled) it was possible to demonstrate a significant AM2233-displacable binding in the Swiss-Webster mice. Future studies will determine if this assay is appropriate for identifying the unknown binding site for AM2233 in the CB1 knockout mice.

  11. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    International Nuclear Information System (INIS)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-01-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of [ 3 H]Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in [14C]iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress [an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures], although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results

  12. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  13. In vivo potency revisited - Keep the target in sight.

    Science.gov (United States)

    Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

    2018-04-01

    Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl (L) ), adding in parallel to the turnover (k syn , k deg ) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (k e(RL) ) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L 50 , is then derived. L 50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L 50 is then compared to the dissociation constant K d (target-ligand binding affinity), the conventional Black & Leff potency estimate EC 50

  14. Concentrations of danofloxacin 18% solution in plasma, milk and tissues after subcutaneous injection in dairy cows

    International Nuclear Information System (INIS)

    Mestorino, N.; Marchetti, M.L.; Turic, E.; Pesoa, J.; Errecalde, J.

    2009-01-01

    Danofloxacin is a fluoroquinolone developed for use in veterinary medicine. Its concentrations and pharmacokinetic profile in plasma, milk and tissues of lactating dairy cows were determined, and its milk withdrawal time (WT) calculated. Twenty-one dairy cows received a single subcutaneous administration of 18% mesylate danofloxacin salt (6 mg kg -1 ). Plasma and milk samples were obtained at different times until 48 h. Groups of three animals were sacrificed at different post-administration times and tissue samples (mammary gland, uterus, duodenum, jejunum, ileum, colon and mesenteric lymph nodes) obtained. Danofloxacin concentrations were determined by liquid chromatography with fluorescence detection. The milk WT was calculated by the Time to Safe Concentration method (Software WTM 1.4, EMEA). Danofloxacin was rapidly absorbed and its distribution from plasma to all sampled tissues and milk was extensive. Milk and tissues concentrations were several times above those found in plasma. Plasma area under the curve (AUCp) was 9.69 μg h mL -1 and its elimination half life (T β 1/2 ) was 12.53 h. AUC values for the various tissues and milk greatly exceeded AUCp. T β 1/2 from milk and tissues ranged between 4.57 and 21.91 h and the milk withdrawal time was 73.48 h. The reported results support the potential use of danofloxacin in the treatment of mastitis and other infections in milk cows with 3 days of withdrawal

  15. The principles of quantification applied to in vivo proton MR spectroscopy

    International Nuclear Information System (INIS)

    Helms, Gunther

    2008-01-01

    Following the identification of metabolite signals in the in vivo MR spectrum, quantification is the procedure to estimate numerical values of their concentrations. The two essential steps are discussed in detail: analysis by fitting a model of prior knowledge, that is, the decomposition of the spectrum into the signals of singular metabolites; then, normalization of these signals to yield concentration estimates. Special attention is given to using the in vivo water signal as internal reference

  16. In vivo quantification of magnetically labelled cells by MRI relaxometry.

    Science.gov (United States)

    Gimenez, Ulysse; Lajous, Hélène; El Atifi, Michèle; Bidart, Marie; Auboiroux, Vincent; Fries, Pascal Henry; Berger, François; Lahrech, Hana

    2016-11-01

    Cellular MRI, which visualizes magnetically labelled cells (cells*), is an active research field for in vivo cell therapy and tracking. The simultaneous relaxation rate measurements (R 2 *, R 2 , R 1 ) are the basis of a quantitative cellular MRI method proposed here. U937 cells were labelled with Molday ION Rhodamine B, a bi-functional superparamagnetic and fluorescent nanoparticle (U937*). U937* viability and proliferation were not affected in vitro. In vitro relaxometry was performed in a cell concentration range of [2.5 × 10 4 -10 8 ] cells/mL. These measurements show the existence of complementary cell concentration intervals where these rates vary linearly. The juxtaposition of these intervals delineates a wide cell concentration range over which one of the relaxation rates in a voxel of an in vivo image can be converted into an absolute cell concentration. The linear regime was found at high concentrations for R 1 in the range of [10 6 - 2 × 10 8 ] cells/mL, at intermediate concentrations for R 2 in [2.5 × 10 5 - 5 × 10 7 ] cells/mL and at low concentrations for R 2 * in [8 × 10 4 - 5 × 10 6 ] cells/mL. In vivo relaxometry was performed in a longitudinal study, with labelled U937 cells injected into a U87 glioma mouse model. Using in vitro data, maps of in vivo U937* concentrations were obtained by converting one of the in vivo relaxation rates to cell concentration maps. MRI results were compared with the corresponding optical images of the same brains, showing the usefulness of our method to accurately follow therapeutic cell biodistribution in a longitudinal study. Results also demonstrate that the method quantifies a large range of magnetically labelled cells*. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  17. In vivo 7Li and 19F NMR studies of drugs in the brain

    International Nuclear Information System (INIS)

    Komoroski, Richard A.

    1999-01-01

    For various reasons, it is advantageous to measure the concentration of a psychoactive drug in the brain in vivo. Many drugs contain the element fluorine. Using 19 F NMR spectroscopy, we have studied the psychoactive drugs trifluoperazine and fluoxetine in the brain in vivo. Using 7 Li NMR, it is possible to detect lithium ion, used to treat manic depressive illness. We have measured the concentration and distribution of lithium in both human and rat brain in vivo. Measurement of drug levels in the human brain may provide a measure of therapeutic or toxic effects, as well as insight into drug metabolism and mechanism of action. (author)

  18. PASSIVE CAVITATION DETECTION DURING PULSED HIFU EXPOSURES OF EX VIVO TISSUES AND IN VIVO MOUSE PANCREATIC TUMORS

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-01-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been demonstrated to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rarefactional focal pressures (1–12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms, pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KPC mice and closely recapitulate human disease in their morphology. The cavitation threshold, defined at 50 % cavitation probability, was found to vary broadly among the investigated tissues (within 2.5–10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but ex vivo it decreased rapidly and stopped over the first few pulses

  19. Passive cavitation detection during pulsed HIFU exposures of ex vivo tissues and in vivo mouse pancreatic tumors.

    Science.gov (United States)

    Li, Tong; Chen, Hong; Khokhlova, Tatiana; Wang, Yak-Nam; Kreider, Wayne; He, Xuemei; Hwang, Joo Ha

    2014-07-01

    Pulsed high-intensity focused ultrasound (pHIFU) has been shown to enhance vascular permeability, disrupt tumor barriers and enhance drug penetration into tumor tissue through acoustic cavitation. Monitoring of cavitation activity during pHIFU treatments and knowing the ultrasound pressure levels sufficient to reliably induce cavitation in a given tissue are therefore very important. Here, three metrics of cavitation activity induced by pHIFU and evaluated by confocal passive cavitation detection were introduced: cavitation probability, cavitation persistence and the level of the broadband acoustic emissions. These metrics were used to characterize cavitation activity in several ex vivo tissue types (bovine tongue and liver and porcine adipose tissue and kidney) and gel phantoms (polyacrylamide and agarose) at varying peak-rare factional focal pressures (1-12 MPa) during the following pHIFU protocol: frequency 1.1 MHz, pulse duration 1 ms and pulse repetition frequency 1 Hz. To evaluate the relevance of the measurements in ex vivo tissue, cavitation metrics were also investigated and compared in the ex vivo and in vivo murine pancreatic tumors that develop spontaneously in transgenic KrasLSL.G12 D/+; p53 R172 H/+; PdxCretg/+ (KPC) mice and closely re-capitulate human disease in their morphology. The cavitation threshold, defined at 50% cavitation probability, was found to vary broadly among the investigated tissues (within 2.5-10 MPa), depending mostly on the water-lipid ratio that characterizes the tissue composition. Cavitation persistence and the intensity of broadband emissions depended both on tissue structure and lipid concentration. Both the cavitation threshold and broadband noise emission level were similar between ex vivo and in vivo pancreatic tumor tissue. The largest difference between in vivo and ex vivo settings was found in the pattern of cavitation occurrence throughout pHIFU exposure: it was sporadic in vivo, but it decreased rapidly and stopped

  20. Radon and its daughters in vivo

    International Nuclear Information System (INIS)

    Rundo, J.

    1983-01-01

    Some aspects of the behavior of radon and its short-lived daughters in vivo are described and a relationship between the radon exhalation rate and time after a meal is demonstrated. A major but short-lived postprandial increase in the exhalation rate of radon produced from skeletally-deposited radium was observed and a similar effect in exhalation rate of environmental radon by persons containing no radium was noted. Persons living in houses with elevated concentrations of radon may contain sufficient activity for its detection by external gamma-ray counting. Some of the activity observed is due to inhaled daughter-products in the chest, and some to daughter-products associated with and produced by the decay of radon throughout the body. 3 references, 8 figures. (MF)

  1. In vivo nanotoxicity assays in plant models.

    Science.gov (United States)

    Kumari, Mamta; Ernest, Vinita; Mukherjee, Amitava; Chandrasekaran, Natarajan

    2012-01-01

    Increasing application of silver nanoparticles (SNPs) and zinc oxide nanoparticles (nZnO) in consumer products like textiles, cosmetics, washing machines and other household products increases their chance to reach the environment. Intensive research is required to assess the nanoparticles' toxicity to the environmental system. The toxicological effect of nanoparticles has been studied at the miniscule scale and requires intensive research to be conducted to assess its unknown effects. Plants are the primary target species which need to be included to develop a comprehensive toxicity profile for nanoparticles. So far, the mechanisms of toxicity of nanoparticles to the plant system remains largely unknown and little information on the potential uptake of nanoparticles by plants and their subsequent fate within the food chain is available. The phytoxicological behaviour of silver and zinc oxide nanoparticles on Allium cepa and seeds of Zea mays (maize), Cucumis sativus (cucumber) and Lycopersicum esculentum (tomato) was done. The in vitro studies on A. cepa have been done to check the cytotoxicological effects including mitotic index, chromosomal aberrations, vagrant chromosomes, sticky chromosomes, disturbed metaphase, breaks and formation of micronucleus. In vitro and in vivo studies on seed systems exposed to different concentration of nanoparticles dispersion to check phytotoxicity end point as root length, germination effect, adsorption and accumulation of nanoparticles (uptake studies) into the plant systems. In vivo studies in a seed system was done using phytagel medium. Biochemical studies were done to check effect on protein, DNA and thiobarbituric acid reactive species concentration. FT-IR studies were done to analyze the functional and conformational changes in the treated and untreated samples. The toxicological effects of nanoparticles had to be studied at the miniscule scale to address existing environment problems or prevent future problems. The

  2. Comparison of in vivo and ex vivo imaging of the microvasculature with 2-photon fluorescence microscopy

    Science.gov (United States)

    Steinman, Joe; Koletar, Margaret; Stefanovic, Bojana; Sled, John G.

    2016-03-01

    This study evaluates 2-Photon fluorescence microscopy of in vivo and ex vivo cleared samples for visualizing cortical vasculature. Four mice brains were imaged with in vivo 2PFM. Mice were then perfused with a FITC gel and cleared in fructose. The same regions imaged in vivo were imaged ex vivo. Vessels were segmented automatically in both images using an in-house developed algorithm that accounts for the anisotropic and spatially varying PSF ex vivo. Through non-linear warping, the ex vivo image and tracing were aligned to the in vivo image. The corresponding vessels were identified through a local search algorithm. This enabled comparison of identical vessels in vivo/ex vivo. A similar process was conducted on the in vivo tracing to determine the percentage of vessels perfused. Of all the vessels identified over the four brains in vivo, 98% were present ex vivo. There was a trend towards reduced vessel diameter ex vivo by 12.7%, and the shrinkage varied between specimens (0% to 26%). Large diameter surface vessels, through a process termed 'shadowing', attenuated in vivo signal from deeper cortical vessels by 40% at 300 μm below the cortical surface, which does not occur ex vivo. In summary, though there is a mean diameter shrinkage ex vivo, ex vivo imaging has a reduced shadowing artifact. Additionally, since imaging depths are only limited by the working distance of the microscope objective, ex vivo imaging is more suitable for imaging large portions of the brain.

  3. In vivo release of FT-207 from irradiation polymerized composites

    International Nuclear Information System (INIS)

    Xie Huaijiang; Kou Qinghe; Song Juzhong; Peng Tao; Chen Xiaohui; Zhang Dexi

    1999-01-01

    Polymer-drugs composite with long periods of controlled slow release was made by radiation induced polymerization in room temperature. In experiment in vivo, the composite was implanted subcutaneously the back of rabbits. The concentration of 1-(2-tetrahydrofuryl)-5-fluorouracil (FT-207) was determined by HPLC. The results of test showed that the concentration of serum drug is 1.0 μg/mL after 1 week in the polymer-drug composites group. The drug concentration of tissue surrounding the composites is 76.2 +- 10.4 μg/mL. The drug concentration in the far organ (e.g.the lung 1.2 +- 0.5 μg/mL) is lower than the tissue surrounding the composite. The serum drug is higher and shorter time by the routine methods. The serum concentration of FT-207 is lower an retarded by implanted

  4. Formulation Optimization and Ex Vivo and In Vivo Evaluation of Celecoxib Microemulsion-Based Gel for Transdermal Delivery.

    Science.gov (United States)

    Cao, Mengyuan; Ren, Lili; Chen, Guoguang

    2017-08-01

    Celecoxib (CXB) is a poorly aqueous solubility sulfonamide non-steroidal anti-inflammatory drug (NSAID). Hence, the formulation of CXB was selected for solubilization and bioavailability. To find out suitable formulation for microemulsion, the solubility of CXB in triacetin (oil phase), Tween 80 (surfactant), and Transcutol-P (co-surfactant) was screened respectively and optimized by using orthogonal experimental design. The Km value and concentration of oil, S mix , and water were confirmed by pseudo-ternary phase diagram studies and central composite design. One percent carbopol 934 was added to form CXB microemulsion-based gel. The final formulation was evaluated for its appearance, pH, viscosity, stability, drug content determination, globule size, and zeta potential. Its ex vivo drug permeation and the in vivo pharmacokinetic was investigated. Further research was performed to ensure the safety and validity by skin irritation study and in vivo anti-inflammatory activity study. Ex vivo permeation study in mice was designed to compare permeation and transdermal ability between microemulsion formulation and conventional gel. The results revealed that optimized microemulsion-based gel gained higher permeation based on smaller globule size and high drug loading of microemulsion. Transdermal ability was also greatly improved. Bioavailability was compared to market Celebrex® by the in vivo pharmacokinetic study in rabbits. The results indicated that CXB microemulsion-based gel had better bioavailability than Celebrex®.

  5. Ultra flat ideal concentrators of high concentration

    Energy Technology Data Exchange (ETDEWEB)

    Chaves, Julio [IST, Physics Dept., Lisboa (Portugal); INETI-DER, Lisboa (Portugal); Collares-Pereira, Manuel [INETI-DER, Lisboa (Portugal)

    2000-07-01

    A new method for the design of nonimaging devices is presented. Its application to the design of ultra flat compact concentrators is analysed. These new concentrators are based on a combination of two stages: the first one is composed of a large number of small structures placed side by side and the second one is a very compact single device concentrating the radiation to the limit. These devices are ideal for 2D. These compact designs are much more compact than the traditional ones like lens-mirror combinations or parabolic primaries with nonimaging secondaries. Besides, they can be designed for any acceptance angle, while the traditional ones are limited to small acceptance angles. (Author)

  6. Highly concentrating Fresnel lenses

    International Nuclear Information System (INIS)

    Kritchman, E.M.; Friesem, A.A.; Yekutieli, G.

    1979-01-01

    A new type of concave Fresnel lens capable of concentrating solar radiation very near the ultimate concentration limit is considered. The differential equations that describe the lens are solved to provide computed solutions which are then checked by ray tracing techniques. The performance (efficiency and concentration) of the lens is investigated and compared to that of a flat Fresnel lens, showing that the new lens is preferable for concentrating solar radiation. (author)

  7. Solar cell concentrating system

    International Nuclear Information System (INIS)

    Garg, H.P.; Sharma, V.K.; Agarwal, R.K.

    1986-11-01

    This study reviews fabrication techniques and testing facilities for different solar cells under concentration which have been developed and tested. It is also aimed to examine solar energy concentrators which are prospective candidates for photovoltaic concentrator systems. This may provide an impetus to the scientists working in the area of solar cell technology

  8. Rheology of concentrated biomass

    Science.gov (United States)

    J.R. Samaniuk; J. Wang; T.W. Root; C.T. Scott; D.J. Klingenberg

    2011-01-01

    Economic processing of lignocellulosic biomass requires handling the biomass at high solids concentration. This creates challenges because concentrated biomass behaves as a Bingham-like material with large yield stresses. Here we employ torque rheometry to measure the rheological properties of concentrated lignocellulosic biomass (corn stover). Yield stresses obtained...

  9. Development and validation of a solid-phase extraction method coupled to liquid chromatography with fluorescence detection for the determination of fluoroquinolone residues in powdered infant formulae. Application to the analysis of samples from the Spanish and Latin American market.

    Science.gov (United States)

    Rodriguez, E; Moreno-Bondi, M C; Marazuela, M D

    2008-10-31

    This paper describes a new method for the effective extraction, clean-up and chromatographic analysis of residues of four fluoroquinolones (ciprofloxacin, enrofloxacin, danofloxacin and sarafloxacin) in powdered infant formulae and follow-on preparations. Samples were reconstituted following the manufacturer's recommendations and treated with trichloroacetic acid in methanol 10% (w/v) for deproteinization. Two solid-phase extraction cartridges have been evaluated for sample clean-up and preconcentration, Strata Screen A and Strata X and the later provided the best recoveries for all the analytes tested. Chromatographic analysis has been carried out using a polar endcapped column (AQUA C(18)) and fluorescence detection, with lomefloxacin (LOME) as internal standard. Method validation has been performed according to European Commission Decision 2002/657/EC criteria, in terms of linearity, recovery, precision, specificity, decision limit (CC(alpha)) and detection capability (CC(beta)). Typical recoveries ranged between 70 and 110% at levels below and above the maximum residue limits of the target analytes in bovine milk, with an excellent intralab reproducibility (RSDsmarket, using LC-MS/MS as confirmatory technique.

  10. Helicobacter pylori from Peptic Ulcer Patients in Uganda Is Highly Resistant to Clarithromycin and Fluoroquinolones: Results of the GenoType HelicoDR Test Directly Applied on Stool

    Directory of Open Access Journals (Sweden)

    Denish Calmax Angol

    2017-01-01

    Full Text Available Background. Around 70–90% of peptic ulcer disease (PUD is due to Helicobacter pylori and requires treatment with antimicrobials to which these bacteria are susceptible. Common H. pylori diagnostic tests do not provide drug susceptibility data. Using the GenoType HelicoDR PCR test designed for gastric biopsies for simultaneous detection of H. pylori and its resistance to clarithromycin (CLA/fluoroquinolones (FLQ, we present evidence for stool as an optional test specimen and also provide data on prevalence of H. pylori resistance to CLA and FLQ in Uganda. Methods. Stool from 142 symptomatic PUD patients at three hospitals in Kampala was screened for H. pylori using a rapid antigen test. The GenoType HelicoDR test was run on all H. pylori antigen positives to determine PCR positivity and resistance to CLA/FLQ. Results. Thirty-one samples (22% were H. pylori antigen positive, and 21 (68% of these were H. pylori PCR positive. Six of the 21 (29% were resistant to CLA and eight to FLQ (42%, while two gave invalid FLQ resistance results. Conclusion. Stool is a possible specimen for the GenoType HelicoDR test for rapid detection of H. pylori and drug resistance. In Uganda, Helicobacter pylori is highly resistant to CLA and FLQ.

  11. In Vivo and In Vitro Evaluatioon of the Inhibitory Effect of some ...

    African Journals Online (AJOL)

    Haemozoin load in the blood of patients was measured after taking antimalarials or plants extracts. The tested plant extracts were established to reduce HZ concentration in vivo. Haemozoin was extracted from the blood samples of all the malaria positive patients studied by centrifugation and the concentration analyzed ...

  12. Effects of ketotifen on human lymphocytes in vitro and in vivo

    NARCIS (Netherlands)

    Petrasch, S.; van Tits, L. J.; Motulsky, H. J.; Brodde, O. E.; Michel, M. C.

    1993-01-01

    The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on human mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymphocyte proliferation. High ketotifen concentrations also inhibited T-lymphocyte mitogen-

  13. Effect of norfloxacin and moxifloxacin on melanin synthesis and antioxidant enzymes activity in normal human melanocytes.

    Science.gov (United States)

    Beberok, Artur; Wrześniok, Dorota; Otręba, Michał; Miliński, Maciej; Rok, Jakub; Buszman, Ewa

    2015-03-01

    Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.

  14. Evaluating In Vitro-In Vivo Extrapolation of Toxicokinetics.

    Science.gov (United States)

    Wambaugh, John F; Hughes, Michael F; Ring, Caroline L; MacMillan, Denise K; Ford, Jermaine; Fennell, Timothy R; Black, Sherry R; Snyder, Rodney W; Sipes, Nisha S; Wetmore, Barbara A; Westerhout, Joost; Setzer, R Woodrow; Pearce, Robert G; Simmons, Jane Ellen; Thomas, Russell S

    2018-05-01

    Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo TK data available to benchmark these methods are from pharmaceuticals. Here we report on new, in vivo rat TK experiments for 26 non-pharmaceutical chemicals with environmental relevance. Both intravenous and oral dosing were used to calculate bioavailability. These chemicals, and an additional 19 chemicals (including some pharmaceuticals) from previously published in vivo rat studies, were systematically analyzed to estimate in vivo TK parameters (e.g., volume of distribution [Vd], elimination rate). For each of the chemicals, rat-specific HTTK data were available and key TK predictions were examined: oral bioavailability, clearance, Vd, and uncertainty. For the non-pharmaceutical chemicals, predictions for bioavailability were not effective. While no pharmaceutical was absorbed at less than 10%, the fraction bioavailable for non-pharmaceutical chemicals was as low as 0.3%. Total clearance was generally more under-estimated for nonpharmaceuticals and Vd methods calibrated to pharmaceuticals may not be appropriate for other chemicals. However, the steady-state, peak, and time-integrated plasma concentrations of nonpharmaceuticals were predicted with reasonable accuracy. The plasma concentration predictions improved when experimental measurements of bioavailability were incorporated. In summary, HTTK and IVIVE methods are adequately robust to be applied to high throughput in vitro toxicity screening data of environmentally relevant chemicals for prioritizing based on human health risks.

  15. Ex vivo and in vivo diffusion of ropivacaine through spinal meninges: influence of absorption enhancers.

    Science.gov (United States)

    Brandhonneur, Nolwenn; Dollo, Gilles; Ratajczak-Enselme, Maja; Deniau, Anne Laure; Chevanne, François; Estèbe, Jean Pierre; Legrand, Alain; Le Corre, Pascal

    2011-02-14

    Following epidural administration, cerebrospinal fluid bioavailability of local anesthetics is low, one major limiting factor being diffusion across the arachnoid mater barrier. The aim of this study was to evaluate the influence of absorption enhancers on the meningeal permeability of epidurally administered ropivacaine. Five enhancers known for their ability to increase drug permeability via transcellular and/or paracellular pathways, i.e. palmitoyl carnitine, ethylenediaminetetraacetic acid, sodium caprate, dodecylphosphocholine and pentylglycerol, were tested ex vivo on fresh specimen of meninges removed from cervical to lumbar level of rabbit spine following laminectomy and placed in diffusion chambers. Among them, sodium caprate lead to the best permeability improvement for both marker and drug (440% and 112% for mannitol and ropivacaine, respectively) and was therefore selected for in vivo study in a sheep model using microdialysis technique to evaluate epidural and intrathecal ropivacaine concentrations following epidural administration. Resulting dialysate and plasma concentrations were used to calculate pharmacokinetic parameters. Following sodium caprate pre-treatment, ropivacaine intrathecal maximal concentration (Cmax) was 1.6 times higher (78 ± 16 μg ml(-1) vs 129 ± 26 μg ml(-1), p<0.05) but the influence of the absorption enhancer was only effective the first 30 min following ropivacaine injection, as seen with the significantly increase of intrathecal AUC(0-30 min) (1629 ± 437 μg min ml(-1) vs 2477 ± 559 μg min ml(-1), p<0.05) resulting in a bioavailable fraction 130% higher 30 min after ropivavaine administration. Co-administration of local anesthetics with sodium caprate seems to allow a transient and reversible improvement of transmeningeal passage into intrathecal space. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Nanodiamonds for In Vivo Applications.

    Science.gov (United States)

    van der Laan, KiranJ; Hasani, Masoumeh; Zheng, Tingting; Schirhagl, Romana

    2018-05-01

    Due to their unique optical properties, diamonds are the most valued gemstones. However, beyond the sparkle, diamonds have a number of unique properties. Their extreme hardness gives them outstanding performance as abrasives and cutting tools. Similar to many materials, their nanometer-sized form has yet other unique properties. Nanodiamonds are very inert but still can be functionalized on the surface. Additionally, they can be made in very small sizes and a narrow size distribution. Nanodiamonds can also host very stable fluorescent defects. Since they are protected in the crystal lattice, they never bleach. These defects can also be utilized for nanoscale sensing since they change their optical properties, for example, based on temperature or magnetic fields in their surroundings. In this Review, in vivo applications are focused upon. To this end, how different diamond materials are made and how this affects their properties are discussed first. Next, in vivo biocompatibility studies are reviewed. Finally, the reader is introduced to in vivo applications of diamonds. These include drug delivery, aiding radiology, labeling, and use in cosmetics. The field is critically reviewed and a perspective on future developments is provided. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Urinary acetonitrile concentrations correlate with recent smoking behaviour

    NARCIS (Netherlands)

    Pinggera, Germar-Michael; Lirk, Philip; Bodogri, Florian; Herwig, Ralf; Steckel-Berger, Gabriele; Bartsch, Georg; Rieder, Josef

    2005-01-01

    To assess the concentration of acetonitrile (a saturated aliphatic nitrile) in the urine of habitual cigarette smokers and non-smokers, as exposure to smoke can be measured by monitoring ambient air or by in vivo tests, but acetonitrile measured in exhaled breath is reportedly a quantitative marker

  18. Age-related changes in factor VII proteolysis in vivo.

    Science.gov (United States)

    Ofosu, F A; Craven, S; Dewar, L; Anvari, N; Andrew, M; Blajchman, M A

    1996-08-01

    Previous studies have reported that pre-operative plasmas of patients over the age of 40 years who developed post-operative deep vein thrombosis (DVT) had approximately twice the amount of proteolysed factor VII found in plasmas of patients in whom prophylaxis with heparin or low M(r) heparin was successful. These and other studies also reported higher concentrations of thrombin-antithrombin III in pre- and post-operative plasmas of patients who developed post-operative thrombosis than in plasmas of patients in whom prophylaxis was successful. Whether the extent of factor VII proteolysis seen in the patients who developed post-operative DVT is related to the severity of their disease or age is not known. This report investigated age-related changes in the concentrations of total factor VII protein, factor VII zymogen, factor VIIa, tissue factor pathway inhibitor, thrombin-antithrombin III, and prothrombin fragment 1 + 2 in normal plasmas and the relationships between these parameters. With the exception of thrombin-antithrombin III, statistically significant increases in the concentrations of these parameters with age were found. Additionally, the differences between the concentrations of total factor VII protein and factor VII zymogen, an index factor VII proteolysis in vivo, were statistically significant only for individuals over age 40. Using linear regression analysis, a significant correlation was found to exist between the concentrations of plasma factor VIIa and prothrombin fragment 1 + 2. Since factor VIIa-tissue factor probably initiates coagulation in vivo, we hypothesize that the elevated plasma factor VIIa (reflecting a less tightly regulated tissue factor activity and therefore increased thrombin production in vivo) accounts for the high risk for post-operative thrombosis seen in individuals over the age of 40.

  19. Metabolite quantitation in breast cancer by in vivo MR spectroscopy

    International Nuclear Information System (INIS)

    Jagananthan, Naranamangalam R.

    2014-01-01

    A large number of biochemical and imaging investigations are available for the diagnosis of cancer but detection is still a challenging task. Various magnetic resonance imaging (MRI) methods are used for the detection of tumors that gives morphological and functional details. On the other hand, magnetic resonance spectroscopy (MRS) provides metabolites or biochemicals at the molecular level. With technological advancement in MR, it is possible to detect in vivo metabolites from normal and pathological tissues that are present in millimolar concentrations and there are several localization methods available for the same. The commonest cancer in women is the breast cancer and is a leading cause of death among the female population worldwide. The in vivo localized proton MR spectroscopy of normal breast tissues is dominated by a huge lipid with little contribution from water while malignant breast tissues contain high water content. By suppressing the water and fat contribution, it is possible to detect choline containing compounds (tCho) in malignant breast tissues. The parameters obtained from in vivo proton MRS of breast tissues are water-to-fat (W-F) ratio and detection of tCho. tCho has been documented by many workers as a potential marker of breast malignancy. Recently, quantitative assessment of tCho concentration has been reported. There are two methods that are used for quantification of tCho: (a) semi-quantitative method that calculates the signal-to-noise ratio (SNR) of the choline signal; and (b) determination of the absolute concentration of tCho using water as an internal and external reference. Both W-F ratio and tCho concentration have been evaluated as markers for assessment of tumor response to therapy. This talk would cover various MRS methods used for the diagnosis of breast cancer together with the details of the determination of the absolute and relative concentrations of metabolites. (author)

  20. Neurogenic plasma exudation mediates grain dust-induced tissue injury in vivo.

    Science.gov (United States)

    Gao, X P; Von Essen, S; Rubinstein, I

    1997-02-01

    The purpose of this study was to determine whether an aqueous extract of grain sorghum dust (GDE) elicits neurogenic plasma exudation in the oral mucosa in vivo. Using intravital microscopy, we found that GDE elicited significant, concentration-dependent leaky site formation and an increase in clearance of fluorescein isothiocyanate-labeled dextran (FITC-dextran; mol mass 70 kDa) from the hamster cheek pouch (P grain sorghum dust elicits immediate oral mucosa inflammation in vivo.

  1. Comparison of clinical categories for Escherichia coli harboring specific qnr and chromosomal-mediated fluoroquinolone resistance determinants according to CLSI and EUCAST.

    Science.gov (United States)

    Machuca, Jesús; Briales, Alejandra; Díaz-de-Alba, Paula; Martínez-Martínez, Luis; Rodríguez-Martínez, José-Manuel; Pascual, Álvaro

    2016-03-01

    EUCAST breakpoints are more restrictive than those defined by CLSI. This study highlights the discrepancies between CLSI and EUCAST in a well characterized isogenic Escherichia coli collection and their correlations with specific quinolone resistance mechanisms. The greatest number of discrepancies was observed in strains containing 2-4 resistance mechanisms (MIC values on the borderline of clinical resistance). Bearing in mind that quinolones are concentration dependent antimicrobial agents, small changes in MIC may have relevant consequences for treatment outcomes. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  2. Hydrophobicity and charge shape cellular metabolite concentrations.

    Directory of Open Access Journals (Sweden)

    Arren Bar-Even

    2011-10-01

    Full Text Available What governs the concentrations of metabolites within living cells? Beyond specific metabolic and enzymatic considerations, are there global trends that affect their values? We hypothesize that the physico-chemical properties of metabolites considerably affect their in-vivo concentrations. The recently achieved experimental capability to measure the concentrations of many metabolites simultaneously has made the testing of this hypothesis possible. Here, we analyze such recently available data sets of metabolite concentrations within E. coli, S. cerevisiae, B. subtilis and human. Overall, these data sets encompass more than twenty conditions, each containing dozens (28-108 of simultaneously measured metabolites. We test for correlations with various physico-chemical properties and find that the number of charged atoms, non-polar surface area, lipophilicity and solubility consistently correlate with concentration. In most data sets, a change in one of these properties elicits a ~100 fold increase in metabolite concentrations. We find that the non-polar surface area and number of charged atoms account for almost half of the variation in concentrations in the most reliable and comprehensive data set. Analyzing specific groups of metabolites, such as amino-acids or phosphorylated nucleotides, reveals even a higher dependence of concentration on hydrophobicity. We suggest that these findings can be explained by evolutionary constraints imposed on metabolite concentrations and discuss possible selective pressures that can account for them. These include the reduction of solute leakage through the lipid membrane, avoidance of deleterious aggregates and reduction of non-specific hydrophobic binding. By highlighting the global constraints imposed on metabolic pathways, future research could shed light onto aspects of biochemical evolution and the chemical constraints that bound metabolic engineering efforts.

  3. In vitro transcription accurately predicts lac repressor phenotype in vivo in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Matthew Almond Sochor

    2014-07-01

    Full Text Available A multitude of studies have looked at the in vivo and in vitro behavior of the lac repressor binding to DNA and effector molecules in order to study transcriptional repression, however these studies are not always reconcilable. Here we use in vitro transcription to directly mimic the in vivo system in order to build a self consistent set of experiments to directly compare in vivo and in vitro genetic repression. A thermodynamic model of the lac repressor binding to operator DNA and effector is used to link DNA occupancy to either normalized in vitro mRNA product or normalized in vivo fluorescence of a regulated gene, YFP. An accurate measurement of repressor, DNA and effector concentrations were made both in vivo and in vitro allowing for direct modeling of the entire thermodynamic equilibrium. In vivo repression profiles are accurately predicted from the given in vitro parameters when molecular crowding is considered. Interestingly, our measured repressor–operator DNA affinity differs significantly from previous in vitro measurements. The literature values are unable to replicate in vivo binding data. We therefore conclude that the repressor-DNA affinity is much weaker than previously thought. This finding would suggest that in vitro techniques that are specifically designed to mimic the in vivo process may be necessary to replicate the native system.

  4. Analysis of Riboflavin Compounds in the Rabbit Cornea In Vivo.

    Science.gov (United States)

    Hammer, Arthur; Rudaz, Serge; Guinchard, Sylvie; Kling, Sabine; Richoz, Olivier; Hafezi, Farhad

    2016-09-01

    To investigate the composition and concentration of individual riboflavin compounds in the corneal stroma in vivo after soaking with various commercially available riboflavin formulations. Experiments were performed in 26 rabbit corneas in vivo: 24 corneas were soaked with riboflavin formulations for 30 minutes or with 0.9% NaCl for control (n = 2). After treatment, corneas were excised and prepared for ultra-high-pressure liquid chromatography (UHPLC) analysis. Additionally, computational chemical analysis of riboflavin compounds and keratan sulfate were performed. The amount of riboflavin and riboflavin phosphate isomers in cornea decreased by a factor of 10 to 100, when compared to the amount in riboflavin formulations. In particular, we found an inverse relationship in the ratio of riboflavin to riboflavin phosphate isomer concentration between formulations and cornea. The electronegativity and ionization potential of riboflavin and phosphate isomers are different. The inverse relationship observed might be explained by a stronger electronegativity of the phosphate isomers, leading to a stronger repulsion by corneal proteoglycans. Indicating the individual concentration of riboflavin compounds in formulations is more representative than the total riboflavin concentration. Riboflavin formulations and CXL protocols might be improved considering the differences in diffusion and ionization potentials of the different riboflavin compounds.

  5. In vivo counting of uranium

    International Nuclear Information System (INIS)

    Palmer, H.E.

    1985-03-01

    A state-of-the-art radiation detector system consisting of six individually mounted intrinsic germanium planar detectors, each 20 cm 2 by 13 mm thick, mounted together such that the angle of the whole system can be changed to match the slope of the chest of the person being counted, is described. The sensitivity of the system for counting uranium and plutonium in vivo and the precedures used in calibrating the system are also described. Some results of counts done on uranium mill workers are presented. 15 figs., 2 tabs

  6. Underscreening in concentrated electrolytes.

    Science.gov (United States)

    Lee, Alpha A; Perez-Martinez, Carla S; Smith, Alexander M; Perkin, Susan

    2017-07-01

    Screening of a surface charge by an electrolyte and the resulting interaction energy between charged objects is of fundamental importance in scenarios from bio-molecular interactions to energy storage. The conventional wisdom is that the interaction energy decays exponentially with object separation and the decay length is a decreasing function of ion concentration; the interaction is thus negligible in a concentrated electrolyte. Contrary to this conventional wisdom, we have shown by surface force measurements that the decay length is an increasing function of ion concentration and Bjerrum length for concentrated electrolytes. In this paper we report surface force measurements to test directly the scaling of the screening length with Bjerrum length. Furthermore, we identify a relationship between the concentration dependence of this screening length and empirical measurements of activity coefficient and differential capacitance. The dependence of the screening length on the ion concentration and the Bjerrum length can be explained by a simple scaling conjecture based on the physical intuition that solvent molecules, rather than ions, are charge carriers in a concentrated electrolyte.

  7. In vivo and ex vivo EPR detection of spin-labelled ovalbumin in mice.

    Science.gov (United States)

    Abramović, Zrinka; Brgles, Marija; Habjanec, Lidija; Tomasić, Jelka; Sentjurc, Marjeta; Frkanec, Ruza

    2010-10-01

    In this study, spin-labelled ovalbumin (SL-OVA), free or entrapped in liposomes, was administered to mice subcutaneously (s.c.) or intravenously (i.v.) with the aim to determine the conditions for pharmacokinetic studies of spin-labelled proteins by EPR and to measure the time course of SL-OVA distribution in vivo in live mice and ex vivo in isolated organs. Upon s.c. administration, the decay of the EPR signal was followed for 60min at the site of application using an L-band EPR spectrometer. Within this time period, the signal of free SL-OVA was diminished by about 70%. It was estimated with the help of the oxidizing agent K(3)[(FeCN)(6)] that approximately 30% was a consequence of the spin label reduction to EPR non-visible hydroxylamine and about 40% was due to the SL-OVA elimination from the site of measurement. For liposome encapsulated SL-OVA, the intensity diminished only by approx. 40% in the same period, indicating that liposomes successfully protect the protein from reduction. EPR signal could not be detected directly over live mouse organs within 60min after s.c. application of SL-OVA. With the available L-band EPR spectrometer, the measurements at the site of s.c. application are possible if the amount of SL-OVA applied to a mouse is more than 3mg. For the pharmacokinetic studies of the protein distribution in organs after s.c. or i.v. injection the concentration of the spin-labelled protein should be more than 0.5mmol/kg. After i.v. administration, only ex vivo measurements were possible using an X-band EPR spectrometer, since the total amount of SL-OVA was not sufficient for in vivo detection and also because of rapid reduction of nitroxide. After 2min, the protein was preferentially distributed to liver and, to a smaller extent, to spleen.

  8. Concentrating photovoltaic solar panel

    Science.gov (United States)

    Cashion, Steven A; Bowser, Michael R; Farrelly, Mark B; Hines, Braden E; Holmes, Howard C; Johnson, Jr., Richard L; Russell, Richard J; Turk, Michael F

    2014-04-15

    The present invention relates to photovoltaic power systems, photovoltaic concentrator modules, and related methods. In particular, the present invention features concentrator modules having interior points of attachment for an articulating mechanism and/or an articulating mechanism that has a unique arrangement of chassis members so as to isolate bending, etc. from being transferred among the chassis members. The present invention also features adjustable solar panel mounting features and/or mounting features with two or more degrees of freedom. The present invention also features a mechanical fastener for secondary optics in a concentrator module.

  9. Increasing Resistance to Extended-Spectrum Cephalosporins, Fluoroquinolone, and Carbapenem in Gram-Negative Bacilli and the Emergence of Carbapenem Non-Susceptibility in Klebsiella pneumoniae: Analysis of Korean Antimicrobial Resistance Monitoring System (KARMS) Data From 2013 to 2015.

    Science.gov (United States)

    Kim, Dokyun; Ahn, Ji Young; Lee, Chae Hoon; Jang, Sook Jin; Lee, Hyukmin; Yong, Dongeun; Jeong, Seok Hoon; Lee, Kyungwon

    2017-05-01

    National surveillance of antimicrobial resistance becomes more important for the control of antimicrobial resistance and determination of treatment guidelines. We analyzed Korean Antimicrobial Resistance Monitoring System (KARMS) data collected from 2013 to 2015. Of the KARMS participants, 16 secondary or tertiary hospitals consecutively reported antimicrobial resistance rates from 2013 to 2015. Data from duplicate isolates and institutions with fewer than 20 isolates were excluded. To determine the long-term trends, previous KARMS data from 2004 to 2012 were also considered. The prevalence of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium from 2013 to 2015 was 66-72% and 29-31%, respectively. The resistance rates of Escherichia coli to cefotaxime and cefepime gradually increased to 35% and 31%, respectively, and fluoroquinolone resistance reached 48% in 2015. The resistance rates of Klebsiella pneumoniae to cefotaxime, cefepime, and carbapenem were 38-41%, 33-41%, and carbapenem susceptibility rates of E. coli and K. pneumoniae decreased from 100% and 99.3% in 2011 to 99.0% and 97.0% in 2015, respectively. The resistance rate of Pseudomonas aeruginosa to carbapenem increased to 35% and the prevalence of carbapenem-resistant Acinetobacter baumannii increased from 77% in 2013 to 85% in 2015. Between 2013 and 2015, the resistance rates of E. coli to third- and fourth-generation cephalosporins increased continuously, while carbapenem-susceptibility gradually decreased, particularly in K. pneumoniae. The prevalence of carbapenem-resistant P. aeruginosa and A. baumannii increased significantly; therefore, few treatment options remain for these resistant strains. © The Korean Society for Laboratory Medicine

  10. Time-dependent recovery of in vivo binding sites after drug dosing: A method for radiotracer evaluation

    International Nuclear Information System (INIS)

    Kilbourn, Michael R.

    1997-01-01

    The recovery of in vivo binding sites for (±)-α-[ 11 C]methoxytetrabenazine, a radioligand for the monoamine vesicular transporter (VMAT2), was determined in mouse brain at various times following a pharmacological dose of tetrabenazine. Concentrations of in vivo radioligand binding sites progressively increased and had reached control values by 8.5 h, and this recovery was consistent with the pharmacokinetics of the competing drug tetrabenazine and its active metabolite, dihydrotetrabenazine. This study demonstrates a simple experimental protocol of using a single dose of a reversible competing drug and time-dependent measurements of in vivo binding of a radioligand. This protocol is suitable for testing the sensitivity of an in vivo radiotracer for measurement of varying concentrations of in vivo binding sites

  11. Hip implants - Paper VI - Ion concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Sargeant, A. [Department of Biological Sciences, Ohio Northern University, Ada, OH 45810 (United States); Goswami, T. [Department of Mechanical Engineering, Ohio Northern University, Ada, OH 45810 (United States)]. E-mail: t-goswami@onu.edu

    2007-07-01

    Total hip-joint arthroplasty is performed in increasing numbers where it translates to about 0.16-0.2% of population per year in industrial countries. In most cases, an implant is a metallic component articulating with a metal, ceramic or poly-ethylene liner as seen in the case of hip, knee and spine. The metal implants release ions in vivo. Therefore, there is a need to study metallic implants and ions released as a result. Toxic concentrations of ions can lead to many adverse physiological effects, including cytotoxicity, genotoxicity, carcinogenicity, and metal sensitivity. There is a need to map ion concentrations establishing boundaries between normal and toxic levels; which however, does not exist. Reference levels of ion concentrations in body fluids and tissues determined by many studies are compiled, reviewed, and presented in this paper. The concentrations of ions released from different alloys, including cobalt, chromium, nickel, molybdenum titanium, aluminum, and vanadium, are presented in this paper. This paper reviews the literature pertaining to clinical data on metal ion concentrations in patients with metal joint prostheses, and laboratory data on the physiological effects of the metals.

  12. The in vivo measurement of radiocaesium activity in broiler chickens

    International Nuclear Information System (INIS)

    Poeschl, M.; Balas, J.

    2000-01-01

    Contamination of certain areas of Europe with radiocaesium from the Chernobyl accident led to a higher 137 Cs accumulation (i.e. 300-600 Bq kg -1 ) in grain and to potential post-accident contamination of broiler chickens. In future, such contamination may require a simple determination of the 137 Cs activity concentration in broiler chicken meat which would lead to measures for preventing the recommended limits of radionuclide contamination of the meat for human consumption from being exceeded. This paper describes the development of a rapid method for the in vivo monitoring of the broiler chicken using a lead-shielded sodium iodide detector. The method enables simply fixed live chicken to be monitored, the results showing a good correlation (R 2 =0.98) with measurements of meat from chicken previously monitored in vivo prior to slaughter

  13. In vivo proton MR spectroscopy of canine status epilepticus

    International Nuclear Information System (INIS)

    Sandstrom, J.C.; Partington, C.R.; Perman, W.H.

    1988-01-01

    Invasive studies of rodent seizure models have demonstrated twice-normal lactate accumulation at the seizure focus. The authors investigated metabolic changes in canine kainic acid-induced seizures by means of in vivo volume-selective water-suppressed proton MR spectroscopy (MVSTE pulse sequence). Spectra from several experiments are presented demonstrating changes in lactate and MR imaging-visible lipid concentration. Spectra were obtained with interlaced acquisition from the brain and an external standard for relative quantification, with best-case line width of 4 Hz and typical line widths of 7-15 Hz at 1.5 T. Direct injection of NAA and lactate in the brain allowed in vivo identification of resonances

  14. Photovoltaic static concentrator analysis

    Science.gov (United States)

    Almonacid, G.; Luque, A.; Molledo, A. G.

    1984-12-01

    Ray tracing is the basis of the present analysis of truncated bifacial compound parabolic concentrators filled with a dielectric substance, which are of interest in photovoltaic applications where the bifacial cells allow higher static concentrations to be achieved. Among the figures of merit for this type of concentrator, the directional intercept factor plays a major role and is defined as the ratio of the power of the collector to that at the entry aperture, in a lossless concentrator illuminated by light arriving from a given direction. A procedure for measuring outdoor, full size panels has been developed, and a correction method for avoiding the effect of unwanted diffuse radiation during the measurements is presented.

  15. CMAQ predicted concentration files

    Data.gov (United States)

    U.S. Environmental Protection Agency — model predicted concentrations. This dataset is associated with the following publication: Muñiz-Unamunzaga, M., R. Borge, G. Sarwar, B. Gantt, D. de la Paz, C....

  16. Vaginal oxytetracycline concentrations.

    Science.gov (United States)

    Thin, R N; Al Rawi, Z H; Simmons, P D; Treharne, J; Tabaqchali, S

    1979-01-01

    Although tetracycline preparations are widely used in departments of genitourinary medicine, or sexually transmitted diseases clinics, little is known of the concentrations of these preparations in genital secretions. For this reason a microbiological method was used for estimating oxytetracycline concentrations in vaginal secretions. These concentrations varied from 0.6 to 6.5 microgram/ml in 19 women who had had sexual contact with a man with non-specific urethritis and who were taking oxytetracycline dihydrate 250 mg four times daily. They were well in excess of the minimum inhibitory concentration of oxytetracycline (0.2 microgram/ml) for the strains of Chlamydia trachomatis isolated from the patients with positive culture results. Thus, oxytetracycline 250 mg four times daily appears to be a satisfactory regimen for the treatment of chlamydial genital infection in women. PMID:509190

  17. Concentrations of Indicator Organisms

    Data.gov (United States)

    U.S. Environmental Protection Agency — It is a compilation of organism concentrations of 16 sampling events conducted between July 2015 and February 2016. It also includes statistical analysis such as...

  18. Concentrated Differential Privacy

    OpenAIRE

    Dwork, Cynthia; Rothblum, Guy N.

    2016-01-01

    We introduce Concentrated Differential Privacy, a relaxation of Differential Privacy enjoying better accuracy than both pure differential privacy and its popular "(epsilon,delta)" relaxation without compromising on cumulative privacy loss over multiple computations.

  19. Nanomaterials for In Vivo Imaging.

    Science.gov (United States)

    Smith, Bryan Ronain; Gambhir, Sanjiv Sam

    2017-02-08

    In vivo imaging, which enables us to peer deeply within living subjects, is producing tremendous opportunities both for clinical diagnostics and as a research tool. Contrast material is often required to clearly visualize the functional architecture of physiological structures. Recent advances in nanomaterials are becoming pivotal to generate the high-resolution, high-contrast images needed for accurate, precision diagnostics. Nanomaterials are playing major roles in imaging by delivering large imaging payloads, yielding improved sensitivity, multiplexing capacity, and modularity of design. Indeed, for several imaging modalities, nanomaterials are now not simply ancillary contrast entities, but are instead the original and sole source of image signal that make possible the modality's existence. We address the physicochemical makeup/design of nanomaterials through the lens of the physical properties that produce contrast signal for the cognate imaging modality-we stratify nanomaterials on the basis of their (i) magnetic, (ii) optical, (iii) acoustic, and/or (iv) nuclear properties. We evaluate them for their ability to provide relevant information under preclinical and clinical circumstances, their in vivo safety profiles (which are being incorporated into their chemical design), their modularity in being fused to create multimodal nanomaterials (spanning multiple different physical imaging modalities and therapeutic/theranostic capabilities), their key properties, and critically their likelihood to be clinically translated.

  20. In-vivo quantitative measurement

    International Nuclear Information System (INIS)

    Ito, Takashi

    1992-01-01

    So far by positron CT, the quantitative analyses of oxygen consumption rate, blood flow distribution, glucose metabolic rate and so on have been carried out. The largest merit of using the positron CT is the observation and verification of mankind have become easy. Recently, accompanying the rapid development of the mapping tracers for central nervous receptors, the observation of many central nervous receptors by the positron CT has become feasible, and must expectation has been placed on the elucidation of brain functions. The conditions required for in vitro processes cannot be realized in strict sense in vivo. The quantitative measurement of in vivo tracer method is carried out by measuring the accumulation and movement of a tracer after its administration. The movement model of the mapping tracer for central nervous receptors is discussed. The quantitative analysis using a steady movement model, the measurement of dopamine receptors by reference method, the measurement of D 2 receptors using 11C-Racloprode by direct method, and the possibility of measuring dynamics bio-reaction are reported. (K.I.)

  1. Free-radical probes for functional in vivo EPR imaging

    Science.gov (United States)

    Subramanian, S.; Krishna, M. C.

    2007-02-01

    Electron paramagnetic resonance imaging (EPRI) is one of the recent functional imaging modalities that can provide valuable in vivo physiological information on its own merit and aids as a complimentary imaging technique to MRI and PET of tissues especially with respect to in vivo pO II (oxygen partial pressure), redox status and pharmacology. EPR imaging mainly deals with the measurement of distribution and in vivo dynamics and redox changes using special nontoxic paramagnetic spin probes that can be infused into the object of investigation. These spin probes should be characterized by simple EPR spectra, preferably with narrow EPR lines. The line width should be reversibly sensitive to the concentration of in vivo pO II with a linear dependence. Several non-toxic paramagnetic probes, some particulate and insoluble and others water-soluble and infusible (by intravenous or intramuscular injection) have been developed which can be effectively used to quantitatively assess tissue redox status, and tumor hypoxia. Quantitative assessment of the redox status of tissue in vivo is important in investigating oxidative stress, and that of tissue pO II is very important in radiation oncology. Other areas in which EPR imaging and oxymetry may help are in the investigation of tumorangiogenesis, wound healing, oxygenation of tumor tissue by the ingestion of oxygen-rich gases, etc. The correct choice of the spin probe will depend on the modality of measurement (whether by CW or time-domain EPR imaging) and the particular physiology interrogated. Examples of the available spin probes and some EPR imaging applications employing them are presented.

  2. Industrialisation et concentration urbaine

    OpenAIRE

    Kamal , Abdelhak

    2010-01-01

    The aim of this thesis is to analyze the determinants of the urban concentration and their effect at different levels of development. The empirical analysis focuses on the developing countries over the period 1950-2000 grouped by level of per capita income. The results confirm the existence of specific trajectories of urbanization rate and urban primacy which differs meaningfully according to the stage of development considered. Certain factors encourage urbanization and its concentration in ...

  3. Solar concentrators. Concentradores solares

    Energy Technology Data Exchange (ETDEWEB)

    Almanza, R.; Valdes, A.; Lopez, S.

    1981-06-01

    This paper presents different types of geometries used in concentrators. Some comments are made on the theoretical and experimental analysis necessary to evaluate the geometries and on the type of laboratory equipment needed to obtain experimental data. At the end of the report a description of how to build parabolic trough mirrors is made. The experience gained by the authors, who have been working in this subject for the past five years, is summarized, showing some of the problems related with such concentrators.

  4. Concentration factors for fish

    International Nuclear Information System (INIS)

    Feldt, W.; Lauer, R.; Melzer, M.; Siebert, W.

    1978-01-01

    Concentration factors are defined as operators allowing to calculate the specific activity of fish meat from a given concentration of an element in the water. This parameter depends among others from the content of stable isotopes and homologues in the different waters. If this parameter is reasonably to be used for model calculations it must be referred to water with all of its content substances, these calculations also being based on this type of 'water'. (orig.) [de

  5. FK concentrator outdoor measurements

    OpenAIRE

    Hernández Sanz, Maikel; Vilaplana, J., J.; Benitez Gimenez, Pablo; Mohedano,, Rubén; Zamora Herranz, Pablo; Miñano Dominguez, Juan Carlos; Mendes Lopes, Joao

    2013-01-01

    The FK is a two-stage optical concentrator for CPV, composed by a Fresnel lens working as POE and a refractive element working as SOE. Both elements perform Köhler integration, for uniform irradiance purposes. The FK has demonstrated that compares very well with other Fresnel-based concentrator optics. Recent on-sun measurements carried out on an FK mono-module prototype have already shown outstanding results, achieving electrical efficiencies over 34%. Further optimization of optical design ...

  6. In vivo dosimetry with L-alpha-alanine

    Energy Technology Data Exchange (ETDEWEB)

    Boey, R; Van Der Velden, K [Industriele Hogeschool van het Gemeenschapsonderwijs Limburg, Hasselt (Belgium); Schaeken, B [Algemeen Ziekenhuis Middelheim, Antwerp (Belgium). Dept. of Radiotherapy

    1995-12-01

    When organic substances are irradiated, stable electrons can be formed. The concentration of these electrons is detected via electron paramagnetic resonance (EPR), a non-destructive form of dosimetry. L-alpha-alanine is extremely suited as a detector because of its high stability and high yield of unpaired electrons. With an EMS 104 spectrometer, we measure the peak-to-peak value of the first derivate of the resonance-spectrum. This value is proportional to the concentration of unpaired electrons and therefore with the absorbed dose. Prior to the in vivo measurements in teletherapy, a calibration curve had to be established. This clearly showed a linear relationship between the EPR-signal and the absorbed dose, except for very low dose where precision was low (20% 1 sd). This indicates that the background signal of the dosimeter is strongly orientation dependent. For this reason it was decided to use pre-irradiated detectors. A number of in vivo measurements has been performed. It was found that the error propagation plays a major role in the calculation of the measured absorbed dose, in the range 1 Gy-6 Gy. Contrary to in vivo measurements in brachytherapy, where higher doses are measured, large uncertainties (30% 1 sd) on the entry dose calculations were observed. For this reason, it is recommended to use a statistical method of reducing this standard deviation to an acceptable level. The proposed method, consisting of 2 detectors and the usage of weight coefficients on our standard deviations, gave promising results. However, theoretical calculations and in vivo measurements show that this method is still not satisfactory to reduce the uncertainty to an acceptable standard in clinical situations.

  7. Sustained release donepezil loaded PLGA microspheres for injection: Preparation, in vitro and in vivo study

    DEFF Research Database (Denmark)

    Guo, Wenjia; Quan, Peng; Fang, Liang

    2015-01-01

    -solvent evaporation method. The optimized formulation which avoided the crushing of microspheres during the preparation process was characterized in terms of particle size, morphology, drug loading and EE, physical state of DP in the matrix and in vitro and in vivo release behavior. DP microspheres were prepared...... release mechanism. After single-dose administration of DP microspheres via subcutaneous injection in rats, the plasma concentration of DP reached peak concentration at 0.50 d, and then declined gradually, but was still detectable at 15 d. A good correlation between in vitro and in vivo data was obtained...

  8. Radical reactions in vivo - an overview

    International Nuclear Information System (INIS)

    Saran, M.; Bors, W.

    1990-01-01

    Generation of radicals in vivo depends on metabolic activities. The reactions are usually influenced by (i) the presence and concentration of oxygen, (ii) the availability of transition metals (effects of binding and compartimentalization), (iii) the level of reductants and antioxidants (e.g. nutritional effects). The effects of radicals are thought to be due to (i) membrane damage (affecting passive or active transport through altered fluidity/function interrelationships, intercellular messenging through modifications in the synthesis of prostaglandins and leukotrienes); (ii) protein damage (e.g. affecting membrane transporters, channel proteins, receptor or regulatory proteins, immunomodulators); (iii) damage to DNA. Defense mechanisms consist of (i) prevention of the 'spreading' of primary damage by low molecular weight antioxidants (e.g. vitamin E, GSH, vitamin C, β-carotene, uric acid); (ii) prevention or limitation of 'secondary' damage by enzymes (e.g. GSH-peroxidase, catalase, superoxide dismutase, DT-diaphorase) and/or chelators; (iii) repair processes, e.g. lipid degradation/membrane repair enzymes (phospholipases, peroxidases, some transferases and reductases), protein disposal or repair enzymes (proteases, GSSG-reductase), DNA degradation or repair enzymes (exonucleases III, endonucleases III and IV, glycosylases, polymerases). Recent hypotheses on a messenging function of the superoxide anion O 2 - are discussed and possible implications of cross-reactions between O 2 - and nitric oxide (endothelium-derived relaxing factor EDRF) are shortly mentioned. (orig.)

  9. Derivative Quotient Spectrophotometry and an Eco-Friendly Micellar Chromatographic Approach with Time-Programmed UV-Detection for the Separation of Two Fluoroquinolones and Phenazopyridine

    Science.gov (United States)

    Tolba, Manar M.; Salim, Mohamed M.

    2016-01-01

    In this study, two analytical approaches were exploited for the resolution of binary mixtures of ciprofloxacin HCl (CIP) or norfloxacin (NOR) and phenazopyridine HCl (PHZ). In the first approach, the amplitudes of the first derivative of the ratio spectra were measured at 267 or 287 nm for CIP and at 268 or 291 nm for NOR. PHZ could be directly determined in the presence of CIP or NOR at 405 nm. The calibration graphs were rectilinear over the ranges of 1.0–16.0 µg/mL for CIP or NOR and 1.0–10.0 µg/mL for PHZ. In the second approach, an accurate, reliable and environmentally nontoxic micellar liquid chromatographic (MLC) method was developed. A good chromatographic separation was achieved using a 150 mm × 4.6 mm i.d., 5 µm particle size Spherisorb ODS-2 column. Eco-friendly mobile phase containing 0.12 M sodium dodecyl sulphate, 0.3% triethylamine and 6% n-butanol in 0.02 M orthophosphoric acid of pH 3.0 was pumped at a flow rate of 1 mL/min. Time programmed UV-detection was applied to allow sensitive determination of the studied drugs. The analytes were eluted without interferences in <10 min. Methocarbamol was used as an internal standard. The MLC method was found to be rectilinear over the concentration range of 0.5–20.0 μg/mL for CIP, NOR or PHZ. These optimized and validated methods were successfully applied for the simultaneous analysis of the studied drugs in their synthetic mixtures and co-formulated tablets. Moreover, the second method was further extended to the determination of these drugs in human urine with direct injection and without any pretreatment. PMID:26867555

  10. Thinking of a Blockchain for VIVO

    OpenAIRE

    garcia, alexander; Lopez, Federico; Conlon, Michael

    2017-01-01

    VIVO is an example of a decentralized system; institutions publish VIVO data just by adhering to a simple data structure in the form of an ontology. Similar to a distributed ledger, VIVO is a decentralized database that is used to maintain a continuously growing list of records. These records aim to include a comprehensive list of scholarly outputs. Although outputs are often described in a single narrative, the published reviewed paper, the research has generat...

  11. In vivo tracing of organophosphorus pesticides in cabbage (Brassica parachinensis) and aloe (Barbadensis)

    Energy Technology Data Exchange (ETDEWEB)

    Qiu, Junlang; Chen, Guosheng; Zhou, Hong; Xu, Jianqiao; Wang, Fuxin; Zhu, Fang, E-mail: ceszf@mail.sysu.edu.cn; Ouyang, Gangfeng, E-mail: cesoygf@mail.sysu.edu.cn

    2016-04-15

    In vivo solid-phase microextraction (SPME) sampling method coupled with gas chromatography–mass spectrometry (GC–MS) analysis was employed to trace the uptake and elimination of organophosphorus pesticides (OPPs) in two kinds of edible plants, cabbage (Brassica parachinensis) and aloe (Barbadensis). The metabolism of fenthion in aloe was also investigated by the liquid chromatography tandem mass spectrometry analysis (LC–MS/MS) to understand the fate of OPPs in living plants better. Transpiration stream concentration factor (TSCF) and depuration rate constants of the OPPs in living plants were obtained therein. The health risk of the OPPs treated aloe was estimated by the maximum residue limit (MRL) approach, and it revealed that the OPPs were rather safe for their fast degradable property. However, peak concentration of fenthion-sulfoxide was found to exceed the MRL and was higher than that of the parent fenthion, which indicated the potential risk of pesticide metabolites. This study highlighted the application of in vivo SPME for contaminant tracing in different living edible plants. The in vivo tracing method is very convenient and can provide more data to evaluate the risk of different pesticides, which are very important for the safety of agriculture production. - Highlights: • In vivo SPME was employed to sample organophosphorus pesticides in vegetables. • Uptake and elimination of OPPs were traced in cabbage and aloe. • In vivo tracing of fenthion demonstrated its metabolites could be rather dangerous. • The risks of OPPs were assessed based on the in vivo tracing data.

  12. In vivo tracing of organophosphorus pesticides in cabbage (Brassica parachinensis) and aloe (Barbadensis)

    International Nuclear Information System (INIS)

    Qiu, Junlang; Chen, Guosheng; Zhou, Hong; Xu, Jianqiao; Wang, Fuxin; Zhu, Fang; Ouyang, Gangfeng

    2016-01-01

    In vivo solid-phase microextraction (SPME) sampling method coupled with gas chromatography–mass spectrometry (GC–MS) analysis was employed to trace the uptake and elimination of organophosphorus pesticides (OPPs) in two kinds of edible plants, cabbage (Brassica parachinensis) and aloe (Barbadensis). The metabolism of fenthion in aloe was also investigated by the liquid chromatography tandem mass spectrometry analysis (LC–MS/MS) to understand the fate of OPPs in living plants better. Transpiration stream concentration factor (TSCF) and depuration rate constants of the OPPs in living plants were obtained therein. The health risk of the OPPs treated aloe was estimated by the maximum residue limit (MRL) approach, and it revealed that the OPPs were rather safe for their fast degradable property. However, peak concentration of fenthion-sulfoxide was found to exceed the MRL and was higher than that of the parent fenthion, which indicated the potential risk of pesticide metabolites. This study highlighted the application of in vivo SPME for contaminant tracing in different living edible plants. The in vivo tracing method is very convenient and can provide more data to evaluate the risk of different pesticides, which are very important for the safety of agriculture production. - Highlights: • In vivo SPME was employed to sample organophosphorus pesticides in vegetables. • Uptake and elimination of OPPs were traced in cabbage and aloe. • In vivo tracing of fenthion demonstrated its metabolites could be rather dangerous. • The risks of OPPs were assessed based on the in vivo tracing data.

  13. Enrofloxacin is able to control Toxoplasma gondii infection in both in vitro and in vivo experimental models.

    Science.gov (United States)

    Barbosa, Bellisa Freitas; Gomes, Angelica Oliveira; Ferro, Eloisa Amália Vieira; Napolitano, Danielle Reis; Mineo, José Roberto; Silva, Neide Maria

    2012-06-08

    Currently, toxoplasmosis is treated with sulfadiazine and pyrimethamine. However, this treatment presents several adverse side effects; thus, there is a critical need for the development and evaluation of new drugs, which do not present the same problems of the standard therapy. Enrofloxacin is a fluoroquinolone antibiotic known to control infection against several bacteria in veterinary medicine. Recently, this drug has demonstrated protective effects against protozoan parasites such as Neospora caninum. The present study aimed to determine the effect of enrofloxacin in the control of Toxoplasma gondii infection. For this purpose, human foreskin fibroblast (HFF) cells were infected with T. gondii RH strain and treated with sulfadiazine, penicillin/streptomycin, pyrimethamine, or enrofloxacin. Following treatment, we analyzed the infection index, parasite intracellular proliferation and the number of plaques. Additionally, tissue parasitism and histological changes were investigated in the brain of Calomys callosus that were infected with T. gondii (ME49 strain) and treated with either sulfadiazine or enrofloxacin. Enrofloxacin was able to reduce the infection index, intracellular proliferation and the number of plaques in HFF cells infected by T. gondii in comparison with untreated or penicillin/streptomycin-treated ones. Enrofloxacin was more protective against T. gondii in HFF infected cells than sulfadiazine treatment (Penrofloxacin or the associations of sulfadiazine plus pyrimethamine, enrofloxacin plus sulfadiazine or enrofloxacin plus pyrimethamine-treatments were able to reduce the plaque numbers in HFF cells infected by T. gondii when compared to medium, penicillin/streptomycin or sulfadiazine alone. In vivo experiments demonstrated that enrofloxacin diminished significantly the tissue parasitism as well as the inflammatory alterations in the brain of C. callosus infected with T. gondii when compared with untreated animals. Based on our findings, it can

  14. In vivo fertilization of banana

    Directory of Open Access Journals (Sweden)

    Taliane Leila Soares

    2014-01-01

    Full Text Available The aim of this research was to study the in vivo fertilization process of banana cultivars. The diploid hybrid (AA 091087-01 was the male progenitor. Flower samples were checked for fertilization from the first to the twentieth day after pollination. The size of the diploid ovules increased gradually at the beginning of the seed formation process. On the other hand, in the AAA triploids (Cavendish subgroup, the not fertilized ovules were aborted. In the AAB triploids (Prata subgroup some ovules were fertilized. The flowers of Grand Naine, Nanicão and 'Pacovan' cultivars presented necrosis in the distal part of the ovary on the first day after pollination. Necrosis can hinder pollen tube growth towards the ovule, which might be related to the low seed yield in 'Pacovan' cultivars and to the absence of seeds in the Cavendish subgroup cultivars.

  15. Photovoltaic solar concentrator

    Science.gov (United States)

    Nielson, Gregory N.; Gupta, Vipin P.; Okandan, Murat; Watts, Michael R.

    2016-03-15

    A photovoltaic solar concentrator is disclosed with one or more transverse-junction solar cells (also termed point contact solar cells) and a lens located above each solar cell to concentrate sunlight onto the solar cell to generate electricity. Piezoelectric actuators tilt or translate each lens to track the sun using a feedback-control circuit which senses the electricity generated by one or more of the solar cells. The piezoelectric actuators can be coupled through a displacement-multiplier linkage to provide an increased range of movement of each lens. Each lens in the solar concentrator can be supported on a frame (also termed a tilt plate) having three legs, with the movement of the legs being controlled by the piezoelectric actuators.

  16. In vivo radiosensitizing effect of nitroimidazole derivative KIN-804

    International Nuclear Information System (INIS)

    Tada, Takuhito; Nakajima, Toshifumi; Onoyama, Yasuto; Murayama, Chieko; Mori, Yomoyuki; Nagasawa, Hideko; Hori, Hitoshi; Inayama, Seiichi

    1994-01-01

    In vivo characteristics of 2-nitroimidazole-1-methylacetohydroxamate (KIN-804), which is a newly developed hypoxic cell radiosensitizer, are presented. The toxicity, pharmacokinetics, and radiosensitizing effect of KIN-804 were studied by in vivo experiments using C3H/He mice bearing the SCCVII tumor. Results were compared with misonidazole (MISO). LD 50 7 of KIN-804 and MISO were 3200 mg/kg and 2000 mg/kg, respectively. The peak concentration of KIN-804 in the tumor occurred 20 min after intraperitoneal injection and reached about 62% of the maximum concentration in the blood. The concentrations in brain and sciatic nerve were very low and clearance from sciatic nerve was rapid. Enhancement ratios of KIN-804 calculated using the growth delay method were 1.22, 1.50, and 1.71 at doses of 50, 100, and 200 mg/kg, respectively, compared with 1.36 for MISO at a dose of 100 mg/kg. In the TCD 50 assay, enhancement ratios at a dose of 200 mg/kg were 1.69 for KIN-804 and 1.52 for MISO, respectively. KIN-804 is a promising radiosensitizer since it shows less toxicity and higher radiosensitizing activity than MISO. 10 refs., 5 figs

  17. Concentrated loads on concrete

    DEFF Research Database (Denmark)

    Lorenzen, Karen Grøndahl; Nielsen, Mogens Peter

    1997-01-01

    This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas are devel......This report deals with concentrated loads on concrete.A new upper bound solution in the axisymmetrical case of a point load in the center of the end face of a cylinder is developed.Based on previous work dealing with failure mechanisms and upper bound solutions, new approximate formulas...

  18. RX: a nonimaging concentrator.

    Science.gov (United States)

    Miñano, J C; Benítez, P; González, J C

    1995-05-01

    A detailed description of the design procedure for a new concentrator, RX, and some examples of it's use are given. The method of design is basically the same as that used in the design of two other concentrators: the RR and the XR [Appl. Opt. 31, 3051 (1992)]. The RX is ideal in two-dimensional geometry. The performance of the rotational RX is good when the average angular spread of the input bundle is small: up to 95% of the power of the input bundle can be transferred to the output bundle (with the assumption of a constant radiance for the rays of the input bundle).

  19. Inhibition of galactosamine cytotoxicity in an in vivo/in vitro hepatocellular toxicity model

    International Nuclear Information System (INIS)

    MacDonald, J.R.; Thayer, K.J.; White, C.

    1987-01-01

    A combined in vivo/in vitro model of galactosamine hepatotoxicity was employed to test whether previously reported cytoprotective actions of cystamine administration on galactosamine-induced hepatic injury in vivo could be attributed to a direct action of cystamine on toxicant-challenged hepatocytes. In this model, male Sprague-Dawley rats received a 400 mg/kg galactosamine challenge via intraperitoneal injection 1 hr prior to portal vein cannulation for hepatocyte isolation. Isolated cells are established in monolayer culture and galactosamine-induced cellular injury is then expressed over the ensuing 24-48 hr in culture. Consistent with the biochemical basis of galactosamine-induced hepatocellular injury in vivo, cytotoxicity could be prevented by in vitro uridine treatments within 3 hr of the in vivo galactosamine challenge, but not when added 12 hr later. Cystamine, in contrast, exhibited a cytoprotective effect even when added to cultures 12 hr after the in vivo toxicant challenge. Post-toxicant cytoprotection by cystamine in vitro was concentration dependent and did not produce an alteration of hepatocyte nonprotein sulfhydryl content. Post-toxicant cytoprotection by uridine and cystamine in this in vivo/in vitro model of toxicity were fully consistent with in vivo protection from galactosamine-induced necrosis by these agents. This model eliminates potential extrahepatic mechanisms for cystamine's hepatoprotective effect and demonstrates a direct cytoprotective action on galactosamine-challenged hepatocytes

  20. In vivo monitoring of heavy metals in man: cadmium and mercury

    International Nuclear Information System (INIS)

    Ellis, K.J.; Vartsky, D.; Cohn, S.H.

    1982-01-01

    Direct in vivo measurements of selected heavy metals is possible by nuclear analytical techniques. In particular, cadmium and mercury are retained in the body in sufficient quantities for their detection by neutron activation analysis. Autopsy data on cadmium of adult male non-smokers living in the US indicates an average body burden of 30 mg by age 50. The distribution of cadmium in the body, however, is nonuniform, approximately 50% being located in the kidneys and liver. The increased concentration of cadmium within these organs has made possible the direct in vivo measurements of this metal by prompt-gamma neutron activation analysis (PGNAA). At present, in vivo determinations of mercury have been performed on phantoms only. These in vivo techniques provide a unique method of obtaining accurate organ burden data in humans that can be related to the toxicological effects of these metals

  1. Single-cell and subcellular pharmacokinetic imaging allows insight into drug action in vivo.

    Science.gov (United States)

    Thurber, Greg M; Yang, Katy S; Reiner, Thomas; Kohler, Rainer H; Sorger, Peter; Mitchison, Tim; Weissleder, Ralph

    2013-01-01

    Pharmacokinetic analysis at the organ level provides insight into how drugs distribute throughout the body, but cannot explain how drugs work at the cellular level. Here we demonstrate in vivo single-cell pharmacokinetic imaging of PARP-1 inhibitors and model drug behaviour under varying conditions. We visualize intracellular kinetics of the PARP-1 inhibitor distribution in real time, showing that PARP-1 inhibitors reach their cellular target compartment, the nucleus, within minutes in vivo both in cancer and normal cells in various cancer models. We also use these data to validate predictive finite element modelling. Our theoretical and experimental data indicate that tumour cells are exposed to sufficiently high PARP-1 inhibitor concentrations in vivo and suggest that drug inefficiency is likely related to proteomic heterogeneity or insensitivity of cancer cells to DNA-repair inhibition. This suggests that single-cell pharmacokinetic imaging and derived modelling improve our understanding of drug action at single-cell resolution in vivo.

  2. In vivo kinetics of intestinal absorption of riboflavin in rats

    International Nuclear Information System (INIS)

    Feder, S.; Daniel, H.; Rehner, G.

    1991-01-01

    To investigate absorption kinetics of riboflavin under in vivo conditions, with blood and lymph circulation intact, the small intestine of anesthetized rats was perfused with [ 14 C]riboflavin in a concentration range between 0.31 and 10.00 mumol/L. Apart from the uptake of riboflavin from the perfusate, passage of the vitamin into the portal (vena portae) and peripheral (vena femoralis) blood was determined. The absorption proved to be a dual process: at low substrate concentrations (less than 2 mumol/L) a saturable component predominated; at higher concentrations simple diffusion was found to be the prevailing uptake mechanism. The apparent transport constant of the saturable component was calculated to be 0.38 mumol/L. [ 14 C]flavin concentrations in the portal and peripheral blood were estimated as a function of the riboflavin concentration of the perfusion media. The dual character of the absorption was reflected by the portal blood flavin levels. Due to the high retaining and equalizing capacity of the liver, the [ 14 C]flavin level of the peripheral blood was relatively low and obeyed saturation kinetics. Constants of elimination, determined by pharmacokinetic calculations, were different for the two blood compartments but independent of the concentration of riboflavin in the perfusion media

  3. Can glycogen be measured by in vivo neutron activation analysis?

    International Nuclear Information System (INIS)

    Sutcliffe, J.F.; Smith, A.H.; King, R.F.G.H.; Smith, M.A.

    1992-01-01

    The object of this note is to examine the feasibility of measuring liver glycogen using in vivo neutron activation analysis. The authors present equations which allow the mass of glycogen to be expressed in terms of the masses of oxygen, hydrogen, carbon and nitrogen. Using the most precise, published measurements of these elements, the standard deviation in the estimate of liver glycogen was 34 g. The magnitude of this error precluded observing changes in liver glycogen which are normally in the range 16 g to 72 g. However, this technique might be useful in detecting transient high concentrations of liver glycogen.(UK)

  4. The effect of radiofrequency ablation on different organs: Ex vivo and in vivo comparative studies

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo Na [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Rhim, Hyunchul, E-mail: rhimhc@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Choi, Dongil; Kim, Young-sun; Lee, Min Woo; Chang, Ilsoo; Lee, Won Jae; Lim, Hyo K. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2011-11-15

    Objective: The purposes of this study are to evaluate the ex vivo and in vivo efficacy of radiofrequency ablation (RFA) on different porcine tissues by the ablation of three different sites simultaneously. Materials and methods: A multichannel RFA system, enables three separate tumors to be ablated simultaneously, was used. RFA procedures were applied to normal porcine liver, kidney, and muscle together ex vivo (n = 12) and in vivo (n = 17). Pre-impedances, defined as baseline systemic impedances of tissues before beginning RFA, and the areas of ablation zones were measured and compared. Results: The areas of ablation zones among three organs had a significant difference in decreasing order as follows: liver, muscle, and kidney in the ex vivo study (p = 0.001); muscle, liver, and kidney in the in vivo study (p < 0.0001). The areas of ablation zones between ex vivo and in vivo had a significant difference in the liver and muscle (each p < 0.05). There was no significant correlation between the areas of ablation zones and pre-impedances in both studies. Conclusions: Renal RFA produced the smallest ablation zone in both in vivo and ex vivo studies. Muscular RFA demonstrated the largest ablation zone in the in vivo study, and hepatic RFA showed the largest ablation zone in the ex vivo study. This variability in the tissues should be considered for performing an optimized RFA for each organ site.

  5. Parabolic solar concentrator

    Science.gov (United States)

    Tecpoyotl-Torres, M.; Campos-Alvarez, J.; Tellez-Alanis, F.; Sánchez-Mondragón, J.

    2006-08-01

    In this work we present the basis of the solar concentrator design, which has is located at Temixco, Morelos, Mexico. For this purpose, this place is ideal due to its geographic and climatic conditions, and in addition, because it accounts with the greatest constant illumination in Mexico. For the construction of the concentrator we use a recycled parabolic plate of a telecommunications satellite dish (NEC). This plate was totally covered with Aluminum. The opening diameter is of 332 cm, the focal length is of 83 cm and the opening angle is of 90°. The geometry of the plate guaranties that the incident beams, will be collected at the focus. The mechanical treatment of the plate produces an average reflectance of 75% in the visible region of the solar spectrum, and of 92% for wavelengths up to 3μm in the infrared region. We obtain up to 2000°C of temperature concentration with this setup. The reflectance can be greatly improved, but did not consider it as typical practical use. The energy obtained can be applied to conditions that require of those high calorific energies. In order to optimize the operation of the concentrator we use a control circuit designed to track the apparent sun position.

  6. A Microfluidic Cell Concentrator

    Science.gov (United States)

    Warrick, Jay; Casavant, Ben; Frisk, Megan; Beebe, David

    2010-01-01

    Cell concentration via centrifugation is a ubiquitous step in many cell culture procedures. At the macroscale, centrifugation suffers from a number of limitations particularly when dealing with small numbers of cells (e.g., less than 50,000). On the other hand, typical microscale methods for cell concentration can affect cell physiology and bias readouts of cell behavior and function. In this paper, we present a microfluidic concentrator device that utilizes the effects of gravity to allow cells to gently settle out of a suspension into a collection region without the use of specific adhesion ligands. Dimensional analysis was performed to compare different device designs and was verified with flow modeling to optimize operational parameters. We are able to concentrate low-density cell suspensions in a microfluidic chamber, achieving a cell loss of only 1.1 ± 0.6% (SD, n=7) with no observed loss during a subsequent cell staining protocol which incorporates ~36 complete device volume replacements. This method provides a much needed interface between rare cell samples and microfluidic culture assays. PMID:20843010

  7. Aluminum concentration in hydrangeas

    International Nuclear Information System (INIS)

    Yanagawa, M.; Haruyama, Y.; Saito, M.

    2008-01-01

    We have been trying to measure concentration of aluminum in Ajisai, Hydrangea macrophylla for these days. But due to bad luck, we have encountered detector trouble for two years in a low. Thus, we have few data to analyze and obtained quite limited results. (author)

  8. Theory of Concentrated Vortices

    DEFF Research Database (Denmark)

    Alekseenko, Sergey; Kuibin, Pavel; Okulov, Valery

    This book presents comprehensive and authoritative coverage of the wide field of concentrated vortices observed in nature and technique. The methods for research of their kinematics and dynamics are considered. Special attention is paid to the flows with helical symmetry. The authors have describ...

  9. Immunomodulatory effect of Moringa peregrina leaves, ex vivo and in vivo study

    Science.gov (United States)

    Al-Oran, Sawsan Atallah; Hassuneh, Mona Rushdie; Al-Qaralleh, Haitham Naief; Rayyan, Walid Abu; Al-Thunibat, Osama Yosef; Mallah, Eyad; Abu-Rayyan, Ahmed; Salem, Shadi

    2017-01-01

    This study was conducted to assess the in vivo and ex vivo immunomodulatory effect of the ethanol leaves extract of Moringa peregrina in Balb/c mice. For this study, five groups of 5 Balb/c mice were given a single acute subtoxic oral dose of the ethanolic extract at 1.13, 11.30, 23.40 and 113.4 mg/kg and the immunomodulatory effect was assessed on the 6th day following the ingestion. In the (non-functional) assessment, the effect of the extract on the body weight, relative lymphoid organ weight, splenic cellularity and peripheral blood hematologic parameters were evaluated. While in the immunomodulation assessment (functional), we investigated the effect of the extract on the proliferative capacity of splenic lymphocytes and peripheral T and B lymphocytes using mitogen blastogenesis, mixed allogeneic MLR and IgM-Plaque forming cells assays. The ingestion of M. peregrina extract caused a significant increase in the body weight, weight and number of cells of spleen and lymph nodes of the treated mice. Furthermore, the count of RBCs, WBCs, platelets, hemoglobin concentration and PCV % were increased by the extract treatment in a dose-dependent manner. M. peregrina enhanced the proliferative responses of splenic lymphocytes for both T cell and B-cell mitogens. Likewise, the mixed lymphocyte reaction MLR assay has revealed a T-cell dependent proliferation enhancement in the extract treated mice. Moreover, the oral administration of M. peregrina leaves extracts significantly increased PFCs/106 splenocytes in a dose-dependent manner. In conclusion, subtoxic acute doses of M. peregrina extract demonstrated significant potential as an immunomodulatory agent even at the lowest dose of 1.13 mg/kg. PMID:29204086

  10. In vivo enzyme activity in inborn errors of metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D. (Clinical Research Centre, Harrow (England))

    1990-08-01

    Low-dose continuous infusions of (2H5)phenylalanine, (1-13C)propionate, and (1-13C)leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD.

  11. In vivo enzyme activity in inborn errors of metabolism

    International Nuclear Information System (INIS)

    Thompson, G.N.; Walter, J.H.; Leonard, J.V.; Halliday, D.

    1990-01-01

    Low-dose continuous infusions of [2H5]phenylalanine, [1-13C]propionate, and [1-13C]leucine were used to quantitate phenylalanine hydroxylation in phenylketonuria (PKU, four subjects), propionate oxidation in methylmalonic acidaemia (MMA, four subjects), and propionic acidaemia (PA, four subjects) and leucine oxidation in maple syrup urine disease (MSUD, four subjects). In vivo enzyme activity in PKU, MMA, and PA subjects was similar to or in excess of that in adult controls (range of phenylalanine hydroxylation in PKU, 3.7 to 6.5 mumol/kg/h, control 3.2 to 7.9, n = 7; propionate oxidation in MMA, 15.2 to 64.8 mumol/kg/h, and in PA, 11.1 to 36.0, control 5.1 to 19.0, n = 5). By contrast, in vivo leucine oxidation was undetectable in three of the four MSUD subjects (less than 0.5 mumol/kg/h) and negligible in the remaining subject (2 mumol/kg/h, control 10.4 to 15.7, n = 6). These results suggest that significant substrate removal can be achieved in some inborn metabolic errors either through stimulation of residual enzyme activity in defective enzyme systems or by activation of alternate metabolic pathways. Both possibilities almost certainly depend on gross elevation of substrate concentrations. By contrast, only minimal in vivo oxidation of leucine appears possible in MSUD

  12. Scattering Solar Thermal Concentrators

    Energy Technology Data Exchange (ETDEWEB)

    Giebink, Noel C. [Pennsylvania State Univ., State College, PA (United States)

    2015-01-31

    This program set out to explore a scattering-based approach to concentrate sunlight with the aim of improving collector field reliability and of eliminating wind loading and gross mechanical movement through the use of a stationary collection optic. The approach is based on scattering sunlight from the focal point of a fixed collection optic into the confined modes of a sliding planar waveguide, where it is transported to stationary tubular heat transfer elements located at the edges. Optical design for the first stage of solar concentration, which entails focusing sunlight within a plane over a wide range of incidence angles (>120 degree full field of view) at fixed tilt, led to the development of a new, folded-path collection optic that dramatically out-performs the current state-of-the-art in scattering concentration. Rigorous optical simulation and experimental testing of this collection optic have validated its performance. In the course of this work, we also identified an opportunity for concentrating photovoltaics involving the use of high efficiency microcells made in collaboration with partners at the University of Illinois. This opportunity exploited the same collection optic design as used for the scattering solar thermal concentrator and was therefore pursued in parallel. This system was experimentally demonstrated to achieve >200x optical concentration with >70% optical efficiency over a full day by tracking with <1 cm of lateral movement at fixed latitude tilt. The entire scattering concentrator waveguide optical system has been simulated, tested, and assembled at small scale to verify ray tracing models. These models were subsequently used to predict the full system optical performance at larger, deployment scale ranging up to >1 meter aperture width. Simulations at an aperture widths less than approximately 0.5 m with geometric gains ~100x predict an overall optical efficiency in the range 60-70% for angles up to 50 degrees from normal. However, the

  13. Absolute calibration in vivo measurement systems

    International Nuclear Information System (INIS)

    Kruchten, D.A.; Hickman, D.P.

    1991-02-01

    Lawrence Livermore National Laboratory (LLNL) is currently investigating a new method for obtaining absolute calibration factors for radiation measurement systems used to measure internally deposited radionuclides in vivo. Absolute calibration of in vivo measurement systems will eliminate the need to generate a series of human surrogate structures (i.e., phantoms) for calibrating in vivo measurement systems. The absolute calibration of in vivo measurement systems utilizes magnetic resonance imaging (MRI) to define physiological structure, size, and composition. The MRI image provides a digitized representation of the physiological structure, which allows for any mathematical distribution of radionuclides within the body. Using Monte Carlo transport codes, the emission spectrum from the body is predicted. The in vivo measurement equipment is calibrated using the Monte Carlo code and adjusting for the intrinsic properties of the detection system. The calibration factors are verified using measurements of existing phantoms and previously obtained measurements of human volunteers. 8 refs

  14. Ex-vivo response to blood products and haemostatic agents after paediatric cardiac surgery

    DEFF Research Database (Denmark)

    Hvas, Anne-Mette; Andreasen, Jo B; Christiansen, Kirsten

    2013-01-01

    cardiac surgery. The haemostatic potential of various factor concentrates (fibrinogen concentrate, recombinant factor VIIa and factor XIII), fresh frozen plasma (FFP), pooled platelets and tranexamic acid was investigated. After surgery, the coagulation profiles revealed significantly prolonged clotting...... of fibrinogen concentrate, FFP or tranexamic acid improved clot stability significantly. Whole blood coagulation was significantly impaired after cardiac surgery in children. Ex-vivo studies showed a total reversal of the coagulopathy after addition of pooled platelets and significantly improved clot stability...... after addition of fibrinogen concentrate, FFP and tranexamic acid, respectively....

  15. In vivo oxidation in remelted highly cross-linked retrievals.

    Science.gov (United States)

    Currier, B H; Van Citters, D W; Currier, J H; Collier, J P

    2010-10-20

    polyethylene materials had no measurable free-radical concentration and no increase in oxidation during shelf storage, these materials were expected to be oxidation-resistant in vivo. However, some remelted highly cross-linked ultra-high molecular weight polyethylene retrievals showed measurable oxidation after an average of more than two years in vivo. This apparent departure from widely expected behavior requires continued study of the process of in vivo oxidation of ultra-high molecular weight polyethylene materials.

  16. Concentric Split Flow Filter

    Science.gov (United States)

    Stapleton, Thomas J. (Inventor)

    2015-01-01

    A concentric split flow filter may be configured to remove odor and/or bacteria from pumped air used to collect urine and fecal waste products. For instance, filter may be designed to effectively fill the volume that was previously considered wasted surrounding the transport tube of a waste management system. The concentric split flow filter may be configured to split the air flow, with substantially half of the air flow to be treated traveling through a first bed of filter media and substantially the other half of the air flow to be treated traveling through the second bed of filter media. This split flow design reduces the air velocity by 50%. In this way, the pressure drop of filter may be reduced by as much as a factor of 4 as compare to the conventional design.

  17. Tritium concentration monitor

    International Nuclear Information System (INIS)

    Shono, Kosuke.

    1991-01-01

    A device for measuring the concentration of tritium in gaseous wastes in a power plant and a nuclear fuel reprocessing plant is reduced in the size and improved in performance. The device of the present invention pressurizes a sampling gas and cools it to a dew point. Water content in the sampling gas cooled to the dew point is condensated and recovered to a fine tube-like water content recovering container. The concentration of the recovered condensates is measured by a tritium density analyzer. With such procedures, since the specimen is pressurized, the dew point can be elevated. Accordingly, the size of the cooling device can be decreased, enabling to contribute to the reduction of the size of the entire device. Further, since the water content recovering device is formed as a fine tube, the area of contact between the specimen gas and the liquid condensated water can be reduced. Accordingly, evaporation of the liquid condensates can be prevented. (I.S.)

  18. Zirconia concentrate chlorination

    International Nuclear Information System (INIS)

    Costa, N.G.; Albuquerque Brocchi, E. de

    1990-01-01

    Chlorination experiments were conducted in order to study the kinetics of gasification of the zirconium oxide present in the zirconia concentrate. The variables studied are temperature (1173 to 1373 K), percentage of reducing agent (12 to 36%) and porosity (22 to 30%). The results indicated a greater influence of temperature and percentage of reducing agent as well as allowed the conclusion that a balance between the levels of these variables is an important factor in the appropriate chlorination conditions. (author)

  19. Thermodynamically efficient solar concentrators

    Science.gov (United States)

    Winston, Roland

    2012-10-01

    Non-imaging Optics is the theory of thermodynamically efficient optics and as such depends more on thermodynamics than on optics. Hence in this paper a condition for the "best" design is proposed based on purely thermodynamic arguments, which we believe has profound consequences for design of thermal and even photovoltaic systems. This new way of looking at the problem of efficient concentration depends on probabilities, the ingredients of entropy and information theory while "optics" in the conventional sense recedes into the background.

  20. Electrolyte Concentrates Treat Dehydration

    Science.gov (United States)

    2009-01-01

    Wellness Brands Inc. of Boulder, Colorado, exclusively licensed a unique electrolyte concentrate formula developed by Ames Research Center to treat and prevent dehydration in astronauts returning to Earth. Marketed as The Right Stuff, the company's NASA-derived formula is an ideal measure for athletes looking to combat dehydration and boost performance. Wellness Brands also plans to expand with products that make use of the formula's effective hydration properties to help treat conditions including heat stroke, altitude sickness, jet lag, and disease.

  1. Chlorination of zirconyte concentrate

    International Nuclear Information System (INIS)

    Costa, N.G.

    1988-01-01

    Chlorination experiments with zirconyte concentrate were carried out in order to study the effects of temperature, percentage of reducing agent and porosity on the gasification of ZrO 2 for 10 and 20 minutes of reaction. Factorial analysis was applied and the results indicated that temperature and percentage of reducing agent were the two only variables effecting the ZrO 2 gasification. (author) [pt

  2. Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity

    Science.gov (United States)

    Ferguson, David P.; Dangott, Lawrence J.; Lightfoot, J. Timothy

    2014-01-01

    Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity. PMID:24806225

  3. Pharmacological Modulation of Hemodynamics in Adult Zebrafish In Vivo.

    Directory of Open Access Journals (Sweden)

    Daniel Brönnimann

    Full Text Available Hemodynamic parameters in zebrafish receive increasing attention because of their important role in cardiovascular processes such as atherosclerosis, hematopoiesis, sprouting and intussusceptive angiogenesis. To study underlying mechanisms, the precise modulation of parameters like blood flow velocity or shear stress is centrally important. Questions related to blood flow have been addressed in the past in either embryonic or ex vivo-zebrafish models but little information is available for adult animals. Here we describe a pharmacological approach to modulate cardiac and hemodynamic parameters in adult zebrafish in vivo.Adult zebrafish were paralyzed and orally perfused with salt water. The drugs isoprenaline and sodium nitroprusside were directly applied with the perfusate, thus closely resembling the preferred method for drug delivery in zebrafish, namely within the water. Drug effects on the heart and on blood flow in the submental vein were studied using electrocardiograms, in vivo-microscopy and mathematical flow simulations.Under control conditions, heart rate, blood flow velocity and shear stress varied less than ± 5%. Maximal chronotropic effects of isoprenaline were achieved at a concentration of 50 μmol/L, where it increased the heart rate by 22.6 ± 1.3% (n = 4; p < 0.0001. Blood flow velocity and shear stress in the submental vein were not significantly increased. Sodium nitroprusside at 1 mmol/L did not alter the heart rate but increased blood flow velocity by 110.46 ± 19.64% (p = 0.01 and shear stress by 117.96 ± 23.65% (n = 9; p = 0.03.In this study, we demonstrate that cardiac and hemodynamic parameters in adult zebrafish can be efficiently modulated by isoprenaline and sodium nitroprusside. Together with the suitability of the zebrafish for in vivo-microscopy and genetic modifications, the methodology described permits studying biological processes that are dependent on hemodynamic alterations.

  4. The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin

    OpenAIRE

    Brander, Susanne M.; He, Guochun; Smalling, Kelly L.; Denison, Michael S.; Cherr, Gary N.

    2012-01-01

    Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. We evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Men...

  5. Estimating Likelihood of Fetal In Vivo Interactions Using In Vitro HTS Data (Teratology meeting)

    Science.gov (United States)

    Tox21/ToxCast efforts provide in vitro concentration-response data for thousands of compounds. Predicting whether chemical-biological interactions observed in vitro will occur in vivo is challenging. We hypothesize that using a modified model from the FDA guidance for drug intera...

  6. In vitro and in vivo effect of Citrus limon essential oil against sarcoptic mange in rabbits

    Science.gov (United States)

    The effect of lemon oil (Citrus limon) on Sarcoptes scabiei var. cuniculi was evaluated in vitro and in vivo. The mite samples were collected from naturally infected rabbits. The lemon oil was prepared in six concentrations by dilution with distilled water (2.5, 5, 10, 20, 50, and 100 %). In vitro a...

  7. Ex-vivo evaluation of crab shell chitosan as absorption enhancer in ...

    African Journals Online (AJOL)

    This study was aimed at evaluating crab shell chitosan as absorption enhancer in ciprofloxacin tablet formulation using the ex-vivo model. Six batches of ciprofloxacin tablets containing varying concentrations of crab shell-derived chitosan ranging from 0 to 5% w/w at 1% w/w intervals were produced. Batch CTS-0 ...

  8. Evaluation of the in vivo and ex vivo optical properties in a mouse ear model

    Energy Technology Data Exchange (ETDEWEB)

    Salomatina, E; Yaroslavsky, A N [Wellman Center for Photomedicine, 40 Blossom Street, Boston, MA 02114 (United States)], E-mail: Yaroslav@helix.mgh.harvard.edu

    2008-06-07

    Determination of in vivo optical properties is a challenging problem. Absorption and scattering measured ex vivo are often used for in vivo applications. To investigate the validity of this approach, we have obtained and compared the optical properties of mouse ears in vivo and ex vivo in the spectral range from 370 to 1650 nm. Integrating sphere spectrophotometry in combination with the inverse Monte Carlo technique was employed to determine absorption coefficients, {mu}{sub a}, scattering coefficients, {mu}{sub s}, and anisotropy factors, g. Two groups of mice were used for the study. The first group was measured in vivo and ex vivo within 5-10 min post mortem. The second group was measured in vivo and ex vivo every 24 h for up to 72 h after sacrifice. Between the measurements the tissues were kept at 4 deg. C wrapped in a gauze moistened with saline solution. Then the specimens were frozen at -25 deg. C for 40 min, thawed and measured again. The results indicate that the absorption coefficients determined in vivo and ex vivo within 5-10 min post mortem differed considerably only in the spectral range dominated by hemoglobin. These changes can be attributed to rapid deoxygenation of tissue and blood post mortem. Absorption coefficients determined ex vivo up to 72 h post mortem decreased gradually with time in the spectral regions dominated by hemoglobin and water, which can be explained by the continuing loss of blood. Absorption properties of the frozen-thawed ex vivo tissues showed increase in oxygenation, which is likely caused by the release of hemoglobin from hemolyzed erythrocytes. Scattering of the ex vivo tissues decreased gradually with time in the entire spectral range due to the continuing loss of blood and partial cell damage. Anisotropy factors did not change considerably.

  9. In vivo study of central receptors in man using pet

    International Nuclear Information System (INIS)

    Baron, J.C.

    1986-09-01

    Central neurotransmitter systems and receptors are intimately involved in the mechanism of several neurologic and phychiatric disorders. Although neurotransmitter concentration and receptor function can be measured regionnally post-mortem, studies performed during life may provide insight into changes at early stages of the disease as well as follow-up data on, and pharmacological modification of, such changes. Positron Tomography (PET) allows to monitor non-invasively the time-course of regional tissue tracer concentration following administration of a radioactive drug. If the latter is known to interact selectively with specific binding sites, it can be used to probe in vivo the regional distribution and affinity of the receptors involved. As shown in this progress report, several receptor systems can now be studied reliably in humans, using PET

  10. In Vitro and In Vivo SERS Biosensing for Disease Diagnosis

    Directory of Open Access Journals (Sweden)

    T. Joshua Moore

    2018-05-01

    Full Text Available For many disease states, positive outcomes are directly linked to early diagnosis, where therapeutic intervention would be most effective. Recently, trends in disease diagnosis have focused on the development of label-free sensing techniques that are sensitive to low analyte concentrations found in the physiological environment. Surface-enhanced Raman spectroscopy (SERS is a powerful vibrational spectroscopy that allows for label-free, highly sensitive, and selective detection of analytes through the amplification of localized electric fields on the surface of a plasmonic material when excited with monochromatic light. This results in enhancement of the Raman scattering signal, which allows for the detection of low concentration analytes, giving rise to the use of SERS as a diagnostic tool for disease. Here, we present a review of recent developments in the field of in vivo and in vitro SERS biosensing for a range of disease states including neurological disease, diabetes, cardiovascular disease, cancer, and viral disease.

  11. In Vivo Imaging of Molecularly Targeted Phage

    Directory of Open Access Journals (Sweden)

    Kimberly A. Kelly

    2006-12-01

    Full Text Available Rapid identification of in vivo affinity ligands would have far-reaching applications for imaging specific molecular targets, in vivo systems imaging, and medical use. We have developed a high-throughput method for identifying and optimizing ligands to map and image biologic targets of interest in vivo. We directly labeled viable phage clones with far-red fluorochromes and comparatively imaged them in vivo by multichannel fluorescence ratio imaging. Using Secreted Protein Acidic and Rich in Cysteine (osteonectin and vascular cell adhesion molecule-1 as model targets, we show that: 1 fluorescently labeled phage retains target specificity on labeling; 2 in vivo distribution can be quantitated (detection thresholds of ~ 300 phage/mm3 tissue throughout the entire depth of the tumor using fluorescent tomographic imaging; and 3 fluorescently labeled phage itself can serve as a replenishable molecular imaging agent. The described method should find widespread application in the rapid in vivo discovery and validation of affinity ligands and, importantly, in the use of fluorochrome-labeled phage clones as in vivo imaging agents.

  12. Recommendations for safety testing with the in vivo comet assay.

    Science.gov (United States)

    Vasquez, Marie Z

    2012-08-30

    While the in vivo comet assay increases its role in regulatory safety testing, deliberations about the interpretation of comet data continue. Concerns can arise regarding comet assay publications with limited data from non-blind testing of positive control compounds and using protocols (e.g. dose concentrations, sample times, and tissues) known to give an expected effect. There may be a tendency towards bias when the validation or interpretation of comet assay data is based on results generated by widely accepted but non-validated assays. The greatest advantages of the comet assay are its sensitivity and its ability to detect genotoxicity in tissues and at sample times that could not previously be evaluated. Guidelines for its use and interpretation in safety testing should take these factors into account. Guidelines should be derived from objective review of data generated by blind testing of unknown compounds dosed at non-toxic concentrations and evaluated in a true safety-testing environment, where the experimental design and conclusions must be defensible. However, positive in vivo comet findings with such compounds are rarely submitted to regulatory agencies and this data is typically unavailable for publication due to its proprietary nature. To enhance the development of guidelines for safety testing with the comet assay, and with the permission of several sponsors, this paper presents and discusses relevant data from multiple GLP comet studies conducted blind, with unknown pharmaceuticals and consumer products. Based on these data and the lessons we have learned through the course of conducting these studies, I suggest significant adjustments to the current conventions, and I provide recommendations for interpreting in vivo comet assay results in situations where risk must be evaluated in the absence of carcinogenicity or clinical data. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. In vivo plasma concentration for lindane after 6 hour exposure in human skin

    Data.gov (United States)

    U.S. Environmental Protection Agency — Dataset is a time course description of lindane disappearance in blood plasma after dermal exposure in human volunteers. This dataset is associated with the...

  14. Concentrated Solar Thermoelectric Power

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Gang [MIT; Ren, Zhifeng [University of Houston

    2015-07-09

    The goal of this project is to demonstrate in the lab that solar thermoelectric generators (STEGs) can exceed 10% solar-to-electricity efficiency, and STEGs can be integrated with phase-change materials (PCM) for thermal storage, providing operation beyond daylight hours. This project achieved significant progress in many tasks necessary to achieving the overall project goals. An accurate Themoelectric Generator (TEG) model was developed, which included realistic treatment of contact materials, contact resistances and radiative losses. In terms of fabricating physical TEGs, high performance contact materials for skutterudite TE segments were developed, along with brazing and soldering methods to assemble segmented TEGs. Accurate measurement systems for determining device performance (in addition to just TE material performance) were built for this project and used to characterize our TEGs. From the optical components’ side, a spectrally selective cermet surface was developed with high solar absorptance and low thermal emittance, with thermal stability at high temperature. A measurement technique was also developed to determine absorptance and total hemispherical emittance at high temperature, and was used to characterize the fabricated spectrally selective surfaces. In addition, a novel reflective cavity was designed to reduce radiative absorber losses and achieve high receiver efficiency at low concentration ratios. A prototype cavity demonstrated that large reductions in radiative losses were possible through this technique. For the overall concentrating STEG system, a number of devices were fabricated and tested in a custom built test platform to characterize their efficiency performance. Additionally, testing was performed with integration of PCM thermal storage, and the storage time of the lab scale system was evaluated. Our latest testing results showed a STEG efficiency of 9.6%, indicating promising potential for high performance concentrated STEGs.

  15. Censored correlated cytokine concentrations

    DEFF Research Database (Denmark)

    Andersen, Andreas; Benn, Christine Stabell; Jørgensen, Mathias J

    2013-01-01

    ) can be used to describe the relative concentration between two cytokines, and the GMR ratio (GMRR) can be used to compare two groups. The problem is how to estimate GMRRs from censored distributions.We evaluated methods, including simple deletion and substitution, in simulated and real data. One...... stacking method that uses clustered variance-covariance estimation allowing homogeneous (Stackc) or inhomogeneous (Stackh) variances. We compare it with direct estimation of the bivariate Tobit likelihood function (Bitobit) and multiple imputation. We assess sensitivity to inhomogeneity and non...

  16. Concentrating Solar Power Systems

    Science.gov (United States)

    Pitz-Paal, R.

    2017-07-01

    Development of Concentrating Solar Power Systems has started about 40 years ago. A first commercial implementation was performed between 1985 and 1991 in California. However, a drop in gas prices caused a longer period without further deployment. It was overcome in 2007 when new incentive schemes for renewables in Spain and the US enabled a commercial restart. In 2016, almost 100 commercial CSP plants with more than 5GW are installed worldwide. This paper describes the physical background of CSP technology, its technical characteristics and concepts. Furthermore, it discusses system performances, cost structures and the expected advancement.

  17. Uranium concentration in fossils

    International Nuclear Information System (INIS)

    Okano, J.; Uyeda, C.

    1988-01-01

    Recently it is known that fossil bones tend to accumulate uranium. The uranium concentration, C u in fossils has been measured so far by γ ray spectroscopy or by fission track method. The authors applied secondary ion mass spectrometry, SIMS, to detect the uranium in fossil samples. The purpose of this work is to investigate the possibility of semi-quantitative analyses of uranium in fossils, and to study the correlation between C u and the age of fossil bones. The further purpose of this work is to apply SIMS to measure the distribution of C u in fossil teeth

  18. Theory of Concentrated Vortices

    DEFF Research Database (Denmark)

    Alekseenko, Sergey; Kuibin, Pavel; Okulov, Valery

    This book presents comprehensive and authoritative coverage of the wide field of concentrated vortices observed in nature and technique. The methods for research of their kinematics and dynamics are considered. Special attention is paid to the flows with helical symmetry. The authors have describ...... models of vortex structures used for interpretation of experimental data which serve as a ground for development of theoretical and numerical approaches to vortex investigation. Achievements in the fields of stability analysis, waves on vortices and vortex breakdown are also presented....

  19. Changes in antibiotic concentrations and antibiotic resistome during commercial composting of animal manures.

    Science.gov (United States)

    Xie, Wan-Ying; Yang, Xin-Ping; Li, Qian; Wu, Long-Hua; Shen, Qi-Rong; Zhao, Fang-Jie

    2016-12-01

    The over-use of antibiotics in animal husbandry in China and the concomitant enhanced selection of antibiotic resistance genes (ARGs) in animal manures are of serious concern. Thermophilic composting is an effective way of reducing hazards in organic wastes. However, its effectiveness in antibiotic degradation and ARG reduction in commercial operations remains unclear. In the present study, we determined the concentrations of 15 common veterinary antibiotics and the abundances of 213 ARGs and 10 marker genes for mobile genetic elements (MGEs) in commercial composts made from cattle, poultry and swine manures in Eastern China. High concentrations of fluoroquinolones were found in the poultry and swine composts, suggesting insufficient removal of these antibiotics by commercial thermophilic composting. Total ARGs in the cattle and poultry manures were as high as 1.9 and 5.5 copies per bacterial cell, respectively. After thermophilic composting, the ARG abundance in the mature compost decreased to 9.6% and 31.7% of that in the cattle and poultry manure, respectively. However, some ARGs (e.g. aadA, aadA2, qacEΔ1, tetL) and MGE marker genes (e.g. cintI-1, intI-1 and tnpA-04) were persistent with high abundance in the composts. The antibiotics that were detected at high levels in the composts (e.g. norfloxacin and ofloxacin) might have posed a selection pressure on ARGs. MGE marker genes were found to correlate closely with ARGs at the levels of individual gene, resistance class and total abundance, suggesting that MGEs and ARGs are closely associated in their persistence in the composts under antibiotic selection. Our research shows potential disseminations of antibiotics and ARGs via compost utilization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Fluoroquinolone-Resistant Uncomplicated Urinary Tract Infections ...

    African Journals Online (AJOL)

    Of the failures in the group, Proteus mirabilis, Staphylococcus epidermidis and Providencia rettgeri were implicated in 50.0%, 50.0% and 100.0% of the failures, respectively. The clinical outcomes were also good, with cure or improvement for more than 80% of all subjects. About 14% of the study subjects reported at least ...

  1. Kinetic spectrophotometric determination of some fluoroquinolone ...

    African Journals Online (AJOL)

    A simple and sensitive kinetic spectrophotometric method was developed for the determination of some fluoroquinolonea antibiotics; gemifloxacin mesylate, moxifloxacin hydrochloride and gatifloxacin in bulk and in pharmaceutical preparations. The method is based upon a kinetic investigation of the oxidation reaction of ...

  2. Complex concentrate pretreatment

    International Nuclear Information System (INIS)

    Lokken, R.O.; Scheele, R.D.; Strachan, D.M.; Toste, A.P.

    1991-03-01

    After removal of the transuranics (TRU) by the TRUEX process, complex concentrate waste will be grouted for final storage. The purpose of this project, conducted at the Pacific Northwest Laboratory, is to support a future decision to grout the complexant waste without destruction of the organic contents. It has been demonstrated that grouts with acceptable parameters for the Transportable Grout Facility can be made using actual waste. The acceptability of these grouts from a regulatory view seems to be less of a problem than previously. None of the organics found in the waste have been found on the EPA hazardous chemicals list. Two potential problems with the processing of the complex concentrate wastes were identified during the use of the TRUEX process on samples of several milliliters. One was the amount of foam that is generated during acid addition to the alkaline waste. Some of this foam appears to be of a waxy nature but does redissolve when the waste is strongly acid. The second potential problem is that noticeable amounts of NO x gases are generated. No quantitative measure of the NO x gas generation was made. The problem relates to processing the waste in B-plant where there are no facilities to handle NO x gases. 5 refs., 4 figs., 4 tabs

  3. Dual temperature concentration system

    International Nuclear Information System (INIS)

    Spevack, J.S.

    1975-01-01

    In a dual temperature isotope exchange system--exemplified by exchange of deuterium and protium between water and hydrogen sulfide gas in hot and cold towers, in which the feed stream (water) containing the desired isotope is passed through a pair of towers maintained at different temperatures wherein it effects isotope exchange with countercurrently circulated auxiliary fluid (H 2 S) and is impoverished in said isotope and then disposed of, e.g. discharged to waste,--the flow of isotope enriched auxiliary fluid between said towers (hot H 2 S saturated with water vapor) is divided and a part thereof is adjusted in its temperature (to cold tower conditions) and then passed to the auxiliary fluid impoverishing (cold) tower, while the remainder of the divided flow of such enriched auxiliary fluid is passed through a subsequent isotope concentration treatment to produce a product more highly enriched in the desired isotope and wherein it is also adjusted in its temperature and is impoverished in said isotope during said subsequent treatment before it is delivered to the said auxiliary fluid impoverishing (cold) tower. Certain provisions are made for returning to the hot tower liquid carried as vapor by the remainder of the divided flow to the subsequent isotope concentration treatment, for recovering sensible and latent heat, and for reducing passage of auxiliary fluid to waste

  4. Luminescent solar concentrator

    Directory of Open Access Journals (Sweden)

    Tugce Tosun

    2015-07-01

    Full Text Available Luminescent solar concentrator (LSC is a device that has luminescent molecules embedding or topping polymeric or glass waveguide to generate electricity from sunlight with a photovoltaic cell attachment. LSCs can be employed both in small and large scale projects, independent on the direction or angle of the surface with respect to the sun, promising more freedom for integration in urban environments compared to the traditional PV systems. The aim of the SEB&C PDEng project is to investigate the applicability of this innovative technology in the built environment and to bridge the gap of knowledge linking societal, design and technological aspects. The final goal is to exhibit potential application concepts of LSC developed by co-creative methods at SPARK campus which is a hub for open innovation in built environment. Necessity of a paradigm shift towards sustainable and smart cities came into being due to the significant increase in energy demand of the buildings. The challenge is to increase renewable sources in the energy mix while designing aesthetic environments. Thus, building integrated renewable energy technologies represent a great opportunity to help overcome this current challenge. Smart energy, energy efficiency and use of renewable sources are key aspects to be considered nowadays and many innovative technologies need further exploitation to be commercially viable, such as luminescent solar concentrator.

  5. Neratinib reverses ATP-binding cassette B1-mediated chemotherapeutic drug resistance in vitro, in vivo, and ex vivo.

    Science.gov (United States)

    Zhao, Xiao-qin; Xie, Jing-dun; Chen, Xing-gui; Sim, Hong May; Zhang, Xu; Liang, Yong-ju; Singh, Satyakam; Talele, Tanaji T; Sun, Yueli; Ambudkar, Suresh V; Chen, Zhe-Sheng; Fu, Li-wu

    2012-07-01

    Neratinib, an irreversible inhibitor of epidermal growth factor receptor and human epidermal receptor 2, is in phase III clinical trials for patients with human epidermal receptor 2-positive, locally advanced or metastatic breast cancer. The objective of this study was to explore the ability of neratinib to reverse tumor multidrug resistance attributable to overexpression of ATP-binding cassette (ABC) transporters. Our results showed that neratinib remarkably enhanced the sensitivity of ABCB1-overexpressing cells to ABCB1 substrates. It is noteworthy that neratinib augmented the effect of chemotherapeutic agents in inhibiting the growth of ABCB1-overexpressing primary leukemia blasts and KBv200 cell xenografts in nude mice. Furthermore, neratinib increased doxorubicin accumulation in ABCB1-overexpressing cell lines and Rhodamine 123 accumulation in ABCB1-overexpressing cell lines and primary leukemia blasts. Neratinib stimulated the ATPase activity of ABCB1 at low concentrations but inhibited it at high concentrations. Likewise, neratinib inhibited the photolabeling of ABCB1 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner (IC(50) = 0.24 μM). Neither the expression of ABCB1 at the mRNA and protein levels nor the phosphorylation of Akt was affected by neratinib at reversal concentrations. Docking simulation results were consistent with the binding conformation of neratinib within the large cavity of the transmembrane region of ABCB1, which provides computational support for the cross-reactivity of tyrosine kinase inhibitors with human ABCB1. In conclusion, neratinib can reverse ABCB1-mediated multidrug resistance in vitro, ex vivo, and in vivo by inhibiting its transport function.

  6. The 4-vessel Sampling Approach to Integrative Studies of Human Placental Physiology In Vivo.

    Science.gov (United States)

    Holme, Ane M; Holm, Maia B; Roland, Marie C P; Horne, Hildegunn; Michelsen, Trond M; Haugen, Guttorm; Henriksen, Tore

    2017-08-02

    The human placenta is highly inaccessible for research while still in utero. The current understanding of human placental physiology in vivo is therefore largely based on animal studies, despite the high diversity among species in placental anatomy, hemodynamics and duration of the pregnancy. The vast majority of human placenta studies are ex vivo perfusion studies or in vitro trophoblast studies. Although in vitro studies and animal models are essential, extrapolation of the results from such studies to the human placenta in vivo is uncertain. We aimed to study human placenta physiology in vivo at term, and present a detailed protocol of the method. Exploiting the intraabdominal access to the uterine vein just before the uterine incision during planned cesarean section, we collect blood samples from the incoming and outgoing vessels on the maternal and fetal sides of the placenta. When combining concentration measurements from blood samples with volume blood flow measurements, we are able to quantify placental and fetal uptake and release of any compound. Furthermore, placental tissue samples from the same mother-fetus pairs can provide measurements of transporter density and activity and other aspects of placental functions in vivo. Through this integrative use of the 4-vessel sampling method we are able to test some of the current concepts of placental nutrient transfer and metabolism in vivo, both in normal and pathological pregnancies. Furthermore, this method enables the identification of substances secreted by the placenta to the maternal circulation, which could be an important contribution to the search for biomarkers of placenta dysfunction.

  7. Gamma-ray mutagenesis of cultured mammalian cells in vitro and in vivo

    International Nuclear Information System (INIS)

    Suzuki, Norio; Okada, Shigefumi

    1977-01-01

    The in vitro assay system used to study the reversion of L5178Y-Ala32 cells from an alanine requiring state to a non-requiring state, has been modified in order to be of use in selected in vivo systems. Gamma-ray induced mutations were compared between cells cultured in vitro and those grown in vivo in the intraperitoneal cavity of mice. The expression time was chosen to be 2 days for cells grown in vitro and 5 days for those grown in vivo. The dose-response curve can be described as cumulative for cells grown in vitro and linear for those grown in vivo. A doserate effect was observed in both systems. The cells grown in vivo were less sensitive to γ-rays with respect to both mutation rate per rad and cell killing as compared to cells grown in vitro. The delayed expression and reduced sensitivity of cells in vivo with respect to induced mutation may be due to factors such as hypoxia and/or reduced availability of essential nutrients. Sensitization in vitro by BUdR was detectable at a concentration as low as 10 -6 M, using an exposure time of 15 h. Under these conditions, BUdR alone did not induce any observable mutations

  8. Development of Novel Formulations to Enhance in Vivo Transdermal Permeation of Tocopherol

    Directory of Open Access Journals (Sweden)

    Nada Aly H.

    2014-09-01

    Full Text Available Tocopherol represents a big challenge for transdermal permeation owing to its extreme hydrophobicity and large molecular mass. The aim of the present study was to develop alpha-tocopherol (T topical formulations and evaluate their ex vivo and in vivo permeation. Franz diffusion cells were used for ex vivo permeation, and neonatal rats were used for in vivo permeation. Seven gel formulations and 21 liquid formulations were investigated for physical stability, viscosity and permeation of T. Analysis of T was performed by a validated HPLC method using a UV detector. The ex vivo permeation from gel and emulsion formulations was very poor (0.001-0.015 %. Highest permeation was observed from monophasic liquid formulations containing dimethyl sulfoxide (DMSO, tocopheryl polyethylene glycols (TPGs, propylene glycol, ethanol and 9.5 % T. The in vivo results demonstrated higher retention in the epidermis compared to subcutaneous tissues, 1377 and 1.13 μg g-1, respectively. Increasing T concentration from 4.8 to 9.5 % did not increase the amount permeated or % of T retained. It was concluded that simple solutions of T in the presence of DMSO and TPGs were more promising systems for effective transdermal permeation compared to gel, emulsion or oleaginous systems.

  9. In-vivo singlet oxygen threshold doses for PDT.

    Science.gov (United States)

    Zhu, Timothy C; Kim, Michele M; Liang, Xing; Finlay, Jarod C; Busch, Theresa M

    2015-02-01

    Dosimetry of singlet oxygen ( 1 O 2 ) is of particular interest because it is the major cytotoxic agent causing biological effects for type-II photosensitizers during photodynamic therapy (PDT). An in-vivo model to determine the singlet oxygen threshold dose, [ 1 O 2 ] rx,sh , for PDT was developed. An in-vivo radiation-induced fibrosarcoma (RIF) tumor mouse model was used to correlate the radius of necrosis to the calculation based on explicit PDT dosimetry of light fluence distribution, tissue optical properties, and photosensitizer concentrations. Inputs to the model include five photosensitizer-specific photochemical parameters along with [ 1 O 2 ] rx,sh . Photosensitizer-specific model parameters were determined for benzoporphyrin derivative monoacid ring A (BPD) and compared with two other type-II photosensitizers, Photofrin ® and m-tetrahydroxyphenylchlorin (mTHPC) from the literature. The mean values (standard deviation) of the in-vivo [ 1 O 2 ] rx,sh are approximately 0.56 (0.26) and 0.72 (0.21) mM (or 3.6×10 7 and 4.6×10 7 singlet oxygen per cell to reduce the cell survival to 1/e) for Photofrin ® and BPD, respectively, assuming that the fraction of generated singlet oxygen that interacts with the cell is 1. While the values for the photochemical parameters (ξ, σ, g , β) used for BPD were preliminary and may need further refinement, there is reasonable confidence for the values of the singlet oxygen threshold doses. In comparison, the [ 1 O 2 ] rx,sh value derived from in-vivo mouse study was reported to be 0.4 mM for mTHPC-PDT. However, the singlet oxygen required per cell is reported to be 9×10 8 per cell per 1/ e fractional kill in an in-vitro mTHPC-PDT study on a rat prostate cancer cell line (MLL cells) and is reported to be 7.9 mM for a multicell in-vitro EMT6/Ro spheroid model for mTHPC-PDT. A theoretical analysis is provided to relate the number of in-vitro singlet oxygen required per cell to reach cell killing of 1/ e to in-vivo singlet

  10. Comparison of In Vitro Assays in Selecting Radiotracers for In Vivo P-Glycoprotein PET Imaging

    Directory of Open Access Journals (Sweden)

    Renske M. Raaphorst

    2017-09-01

    Full Text Available Positron emission tomography (PET imaging of P-glycoprotein (P-gp in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer´s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized, are usually performed at micromolar concentration, causing often discrepant in vivo and in vitro data. We had in vivo rodent PET data of [11C]verapamil, (R-N-[18F]fluoroethylverapamil, (R-O-[18F]fluoroethyl-norverapamil, [18F]MC225 and [18F]MC224 and we included also two new molecules [18F]MC198 and [18F]KE64 in this study. To improve the predictive value of in vitro assays, we labeled all the tracers with tritium and performed bidirectional substrate transport assay in MDCKII-MDR1 cells at three different concentrations (0.01, 1 and 50 µM and also inhibition assay with P-gp inhibitors. As a comparison, we used non-radioactive molecules in transport assay in Caco-2 cells at a concentration of 10 µM and in calcein-AM inhibition assay in MDCKII-MDR1 cells. All the P-gp substrates were transported dose-dependently. At the highest concentration (50 µM, P-gp was saturated in a similar way as after treatment with P-gp inhibitors. Best in vivo correlation was obtained with the bidirectional transport assay at a concentration of 0.01 µM. One micromolar concentration in a transport assay or calcein-AM assay alone is not sufficient for correct in vivo prediction of substrate P-gp PET ligands.

  11. [Antimycotic activity in vitro and in vivo of 5-fluorocytosine on pathogenic strains of Candida albicans and Cryptococcus neoformans].

    Science.gov (United States)

    Costa, A L; Valenti, A; Costa, G; Calogero, F

    1976-01-01

    The authors have analyzed the 5 Fluoro Cytosine (5FC) activity on strains of Candida albicans and Criptococcus neoformans, both in vitro and in vivo. In vitro the minimal inhibitory concentration (MIC) was determined; in vivo tests of pathogenicity on rabbit and mouse have been executed. The various findings obtained have shown a strong activity of the 5FC on strains of Candida and Criptococcus.

  12. Pushing concentration of stationary solar concentrators to the limit.

    Science.gov (United States)

    Winston, Roland; Zhang, Weiya

    2010-04-26

    We give the theoretical limit of concentration allowed by nonimaging optics for stationary solar concentrators after reviewing sun- earth geometry in direction cosine space. We then discuss the design principles that we follow to approach the maximum concentration along with examples including a hollow CPC trough, a dielectric CPC trough, and a 3D dielectric stationary solar concentrator which concentrates sun light four times (4x), eight hours per day year around.

  13. Lymphotoxin prevention of diethylnitrosamine carcinogenesis in vivo

    International Nuclear Information System (INIS)

    Ransom, J.H.; Evans, C.H.; DiPaolo, J.A.

    1982-01-01

    Development of intervention measures to control cancer would be facilitated by being able to monitor in vivo carcinogenesis by in vitro quantitation of early indices of neoplastic transformation to assess the in vivo effectiveness of preventive-therapeutic measures. Pregnant Syrian golden hamsters were used in an in vivo-in vitro transplacental model of carcinogenesis to determine the extent that in vivo administration of immunologic hormone preparations along with chemical carcinogen would prevent morphologic transformation assessed in vitro. Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation. The frequency of morphologically transformed colonies was assessed after 7 days of growth. Cloning efficiency and mean transformation frequency after DENA exposure were 3.6% and 1 X 10(-4) per cell seeded, respectively. The ip injection of an immunologic hormone preparation reduced the transformation frequency by 46%. The hormone preparation, containing 10,000 U of lymphotoxin but no detectable interferon, was the ultrafiltered lymphokines (greater than 10,000 mol wt) from phytohemagglutinin-stimulated hamster peritoneal leukocytes. The effect of lymphotoxin on cocarcinogenic exposure of fetal cells to DENA in vivo followed by X-irradiation in vitro was also determined. Cells exposed to 250 rad in vitro had a cloning efficiency of 0.5% and a transformation frequency of 0.4 X 10(-4) per cell seeded. After DENA injection and X-irradiation, the transformation frequency increased to 1 X 10(-4) and was inhibited 64% by lymphotoxin in vivo. Thus immunologic hormones (e.g., lymphotoxin) can prevent carcinogenesis in vivo. Furthermore, in vitro quantitation of transformation is a rapid means for evaluating therapeutic and autochthonous effector mechanisms for their ability to prevent or otherwise modulate carcinogenesis in vivo

  14. Muscle-Driven In Vivo Nanogenerator

    KAUST Repository

    Li, Zhou

    2010-05-05

    (Figure Presented) A nanogenerator based on a single piezoelectric fine wire producing an alternating current (AC) is successfully used for the harvesting of biomechanical energy under in vivo conditions. We demonstrate the implanting and working of such a nanogenerator in a live rat where it harvests energy generated by its breathing or heart beating. This study shows the potential of applying these nanogenerators for driving in vivo nanodevices. © 2010 WILEY-VCH Verlag GmbH & Co. KCaA, Weinheim.

  15. Plasma concentrations of misonidazole

    Energy Technology Data Exchange (ETDEWEB)

    Notter, G; Rylander, U; Turesson, I

    1980-10-01

    The plasma concentrations of misonidazole doses between 0.6 and 2.0 g/m/sup 2/ were analyzed in respect to the variation within the same patient and between different patients. Peak plasma levels were observed after 2 hours. The mean plasma levels of misonidazole only at 3 hours were 23.8, 47.0 and 76.5 ..mu..g/ml after misonidazole doses of 0.6, 1.2 g/m/sup 2/, respectively. The half-life of misonidazole only was found to be 8.2 hours for women and 10.5 for men. Good linearity between plasma levels and drug doses was observed after administration of different single doses to the same patient within the dose range 0.6 to 2.0 g/m/sup 2/.

  16. Stress concentration at notches

    CERN Document Server

    Savruk, Mykhaylo P

    2017-01-01

    This book compiles solutions of linear theory of elasticity problems for isotropic and anisotropic bodies with sharp and rounded notches. It contains an overview of established and recent achievements, and presents the authors’ original solutions in the field considered with extensive discussion. The volume demonstrates through numerous, useful examples the effectiveness of singular integral equations for obtaining exact solutions of boundary problems of the theory of elasticity for bodies with cracks and notches. Incorporating analytical and numerical solutions of the problems of stress concentrations in solid bodies with crack-like defects, this volume is ideal for scientists and PhD students dealing with the problems of theory of elasticity and fracture mechanics. Stands as a modern and extensive compendium of solutions to the problems of linear theory of elasticity of isotropic and anisotropic bodies with sharp and rounded notches; Adopts a highly reader-friendly layout of tables, charts, approximation ...

  17. Concentration solar thermal power

    International Nuclear Information System (INIS)

    Livet, F.

    2011-01-01

    As the production of electricity by concentration solar power (CSP) installations is said to be a source of energy for the future, the author discusses past experiments (notably the French Thermis project), and the different techniques which are currently being used. He indicates the regions which appear to be the most appropriate for this technique. He presents the three main techniques: parabolic cylinder, tower, and Stirling cycle installations. He discusses the issue of intermittency. He proposes an assessment of prices and of their evolution, and indicates the investments made in different installations (in Italy, Spain, Germany and Portugal). He comments the case of hybrid installations (sun and gas), evokes the Desertec project proposed by the German industry which comprises a set of hybrid installations. He notices that there is no significant technological evolution for this process

  18. Concentrating solar thermal power.

    Science.gov (United States)

    Müller-Steinhagen, Hans

    2013-08-13

    In addition to wind and photovoltaic power, concentrating solar thermal power (CSP) will make a major contribution to electricity provision from renewable energies. Drawing on almost 30 years of operational experience in the multi-megawatt range, CSP is now a proven technology with a reliable cost and performance record. In conjunction with thermal energy storage, electricity can be provided according to demand. To date, solar thermal power plants with a total capacity of 1.3 GW are in operation worldwide, with an additional 2.3 GW under construction and 31.7 GW in advanced planning stage. Depending on the concentration factors, temperatures up to 1000°C can be reached to produce saturated or superheated steam for steam turbine cycles or compressed hot gas for gas turbine cycles. The heat rejected from these thermodynamic cycles can be used for sea water desalination, process heat and centralized provision of chilled water. While electricity generation from CSP plants is still more expensive than from wind turbines or photovoltaic panels, its independence from fluctuations and daily variation of wind speed and solar radiation provides it with a higher value. To become competitive with mid-load electricity from conventional power plants within the next 10-15 years, mass production of components, increased plant size and planning/operating experience will be accompanied by technological innovations. On 30 October 2009, a number of major industrial companies joined forces to establish the so-called DESERTEC Industry Initiative, which aims at providing by 2050 15 per cent of European electricity from renewable energy sources in North Africa, while at the same time securing energy, water, income and employment for this region. Solar thermal power plants are in the heart of this concept.

  19. Pseudomonas aeruginosa aggregate formation in an alginate bead model system exhibits In Vivo-like characteristics

    DEFF Research Database (Denmark)

    Sønderholm, Majken; Kragh, Kasper Nørskov; Koren, Klaus

    2017-01-01

    similar in size to in vivo aggregates observed ex vivo in cystic fibrosis lungs and chronic wounds. Bacterial aggregates primarily grew in the bead periphery and decreased in size and abundance toward the center of the bead. Microsensor measurements showed that the O2 concentration decreased rapidly...... and flexible in vivo-like biofilm model system, wherein bacterial growth exhibits central features of in vivo biofilms. This was observed by the formation of small cell aggregates in a secondary matrix with O2-limited growth, which was alleviated by the addition of NO3− as an alternative electron acceptor...

  20. Implications of treadmilling for the stability and polarity of actin and tubulin polymers in vivo.

    Science.gov (United States)

    Kirschner, M W

    1980-07-01

    In this report, we examine how the cell can selectively stabilize anchored filaments and suppress spontaneous filament assembly. Because microtubules and actin filaments have an organized distribution in cells, the cell must have a mechanism for suppressing spontaneous and random polymerization. Though the mechanism for suppressing spontaneous polymerization is unknown, an unusual property of these filaments has been demonstrated recently, i.e., under steady-stae conditions, in vitro actin filaments and microtubules can exhibit a flux of subunits through the polymers called "treadmilling." In vivo, however, most, if not all, of these polymers are attached at one end to specific structures and treadmilling should not occur. The function of treadmilling in vivo is, therefore, unclear at present. However, as shown here, the same physicochemical property of coupling assembly to ATP or GTP hydrolysis that leads to treadmilling in vitro can act to selectively stabilize anchored polymers in vivo. I show here that the theory of treadmilling implies that the concentration of subunits necessary for assembly of the nonanchored polymer will in general be higher than the concentration necessary for the assembly of polymers anchored with a specific polarity. This disparity in the monomer concentrations required for assembly can lead to a selective stabilization of anchored polymers and complete suppression of spontaneous polymerization at apparent equilibrium in vivo. It is possible, therefore, that the phenomenon of treadmilling is an in vitro manifestation of a mechanism designed to use ATP or GTP hydrolysis to control the spatial organization of filaments in the cell.

  1. Effects of exogenous carbon monoxide on radiation-induced bystander effect in zebrafish embryos in vivo

    International Nuclear Information System (INIS)

    Choi, V.W.Y.; Wong, M.Y.P.; Cheng, S.H.; Yu, K.N.

    2012-01-01

    In the present work, the influence of a low concentration of exogenous carbon monoxide (CO) liberated from tricarbonylchloro(glycinato)ruthenium (II) (CORM-3) on the radiation induced bystander effect (RIBE) in vivo between embryos of the zebrafish was studied. RIBE was assessed through the number of apoptotic signals revealed on embryos at 25 h post fertilization (hpf). A significant attenuation of apoptosis on the bystander embryos induced by RIBE in a CO concentration dependent manner was observed. - Highlights: ► RIBE between zebrafish embryos in vivo was assessed by the level of apoptosis. ► CO from 10 and 20 μM CORM-3 entirely suppressed the RIBE. ► CO from 5 μM CORM-3 significantly attenuated the level of apoptosis. ► Inactive CORM-3 did not lead to suppression of RIBE. ► Suppression of RIBE by CO depended on the concentration of CORM-3.

  2. Cytotoxicity and in vivo efficacy of a novel antimicrobial peptoid against Staphylococcus pseudintermedius

    DEFF Research Database (Denmark)

    Damborg, Peter Panduro; Skindersø, Mette E; Hansen, Paul Robert

    the in vivo efficacy of a novel peptoid (D2) previously shown to be effective against S. pseudintermedius in vitro. Methods: D2 was subjected to an array of cytotoxicity assays targeting proliferation, cellular stress, apoptosis and cell cycle in Jurkat cells. D2 was then formulated into a gel...... or fusidic acid ointment (day 1-3). Mice were euthanized on day 4. Affected skin was homogenized and CFU/ml was quantified by plate dilution on selective media. Results: D2 did not mediate apoptosis and showed limited effect on Jurkat cell viability and cell cycle at a concentration similar to that used...... time in this murine skin infection model and appeared to colonize well. The lacking effect of D2 in vivo could be due to either a too low concentration or an inhibitory effect of the gel formulation used. The next step will be to find the optimal concentration working in mice and assess toxicity...

  3. In vitro and in vivo antitrypanosomal activity of Xanthium strumarium leaves.

    Science.gov (United States)

    Talakal, T S; Dwivedi, S K; Sharma, S R

    1995-12-15

    Antitrypanosomal activity of crude 50% ethanolic extract of Xanthium strumarium leaves was studied in vitro and in vivo. The extract exhibited trypanocidal activity at all four concentrations tested i.e. 5, 50, 500 and 1000 micrograms/ml, in vitro. In vivo trial revealed that the extract exerted antitrypanosomal effect at dosage of 100, 300 and 1000 mg/kg, intraperitoneally. At 100 and 300 mg/kg doses the survival period of the Trypanosoma evansi infected mice was significantly prolonged. However, the extract was found to be toxic to the animals at 1000 mg/kg dose.

  4. Preparation of selective molybdenum concentrate from collective coppermolybdenum concentrate

    Directory of Open Access Journals (Sweden)

    N. Tusupbaev

    2016-06-01

    Full Text Available The paper considers possibilities of selective separation of the concentrate of copper and molybdenum from a collective copper-molybdenum concentrate of Aktogay deposit using regrinding and conventional flotation reagents. In the case of conventional flotoreagents, the content of molybdenum in a molybdenum concentrate was 8.0% at extraction effectiveness 83.12%. At 27.96% extraction degree of copper, it’s content in the concentrate equaled to 21.3%. After regrinding, molybdenum content in the concentrate was 24.0% at the extraction effectiveness 59.63%, and copper content in the concentrate was 21.9% at the recovery of 61.23%. Thus, the regrinding of a collective copper-molybdenum concentrate resulted in an increase in the content of molybdenum in molybdenum concentrate by 16%, and the copper concentration increased by 0.6%.

  5. In vitro antibiotic susceptibilities of ocular bacteria isolates from the cornea and conjunctiva to moxifloxacin, gatifloxacin and other fluoroquinolones Testes de sensibilidade antimicrobiana de bactérias isoladas da córnea e da conjuntiva à moxifloxacina, gatifloxacina e outras fluoroquinolonas

    Directory of Open Access Journals (Sweden)

    Ana Luisa Höfling-Lima

    2004-12-01

    Full Text Available PURPOSE: To assess and compare the in vitro susceptibility of ocular bacterial isolates to fluoroquinolones, including moxifloxacin and gatifloxacin. METHODS: A total of 154 bacterial ocular isolates from keratitis and conjunctivitis were tested for sensitivity to the studied antibiotics, using the disk diffusion method. RESULTS: Of the 51 corneal isolates, 46 (90.2% were sensitive to ciprofloxacin, 45 (88.2% to ofloxacin and 41 (80.4% to lomefloxacin. All corneal isolates were sensitive to moxifloxacin and gatifloxacin. Of the 103 bacterial conjunctival isolates, 101 (98.1% and 103 (100% were sensitive to gatifloxacin and moxifloxacin, respectively. Two strains of Streptococcus sp viridans group were resistant to gatifloxacin. A total of 82 (79.6% specimens were sensitive to lomefloxacin, 89 (86.4% and 96 (93.2% to ciprofloxacin and ofloxacin, respectively. CONCLUSION: Fourth generation fluoroquinolones, herein exemplified by moxifloxacin and gatifloxacin, seem to be more effective than previous generation fluoroquinolones against frequently encountered organisms isolated from patients with bacterial keratitis and conjunctivitis.OBJETIVOS: Conhecer e comparar a susceptibilidade in vitro de bactérias isoladas do olho à fluoroquinolonas, incluindo moxifloxacina e gatifloxacina. MÉTODOS: Um total de 154 bactérias isoladas de ceratites e conjuntivites foram submetidas a testes de sensibilidade antimicrobiana aos antibióticos usando o método de difusão em disco. RESULTADOS: Das 51 bactérias isoladas da córnea, 46 (90,2% foram sensíveis a ciprofloxacina, 45 (88,2% a ofloxacina e 41 (80,4% a lomefloxacina. Todas as bactérias isoladas da córnea foram sensíveis a moxifloxacina e a gatifloxacina. Das 103 bactérias isoladas da conjuntiva 101 (98,1% e 103 (100% foram sensíveis a gatifloxacina e moxifloxacina, respectivamente. Duas cepas de Streptococcus sp do grupo viridans mostraram-se resistentes à gatifloxacina. Um total de 82 (79,6% esp

  6. ANTIVIRAL ACTIVITY OF DIANTHUS SUPERBUSN L. AGAINST HEPATITIS B VIRUS IN VITRO AND IN VIVO.

    Science.gov (United States)

    Li, Wei-Guo; Wang, He-Qun

    2016-01-01

    Hepatitis is a viral infection of hepatitis B virus (HBV). Limitations of drug used in the management of it opens the interest related to alternative medicine. The given study deals with the antiviral activity of Dianthus superbusn L. (DSL) against HBV in vitro & in vivo . In vitro study liver cell line HepG2.2.15 was used by transinfected it with HBV. Cytotoxicity stduy was performed by using different concentrations of DSL such as 50, 100, 200, 500 & 1000 μg/ml. Anti HBV activity of DSL was estimated by assesing the concentration of HBsAg and HbeAg in cell culture medium by using ELISA. Whereas in vivo study was performed on ducklings and antiviral activity of DSL (100, 200, 400 mg/kg) was confirmed by estimating the serum concentration of HBV DNA and histopathology study of hepatocytes in HBV infected ducklings. Result of the study suggested that >500 μg/ml concentration of hydroalcoholic extract of DSL was found tobe cytotoxic. It was also observed that DSL significantly ( p <0.05) reduces the concentration of antigenes in cell culture media as per the concentration and days of treatment dependent. Moreover in vivo study confirms the anti viral activity of DSL (200 & 400 mg/kg) as it significantly ( p <0.05) decreases the serum concenetration of HBV DNA in HBV infected dukling compared to control group. Histopathology study was also reveals the hepatprotective effect of DSL in HBV infected ducklings. The given study concludes the antiviral activity DSL against HBV by in vitro and in vivo models.

  7. Workplace Concentration of Immigrants

    Science.gov (United States)

    Andersson, Fredrik; García-Pérez, Mónica; Haltiwanger, John; McCue, Kristin; Sanders, Seth

    2014-01-01

    Casual observation suggests that in most U.S. urban labor markets, immigrants have more immigrant coworkers than native-born workers do. While seeming obvious, this excess tendency to work together has not been precisely measured, nor have its sources been quantified. Using matched employer–employee data from the U.S. Census Bureau Longitudinal Employer-Household Dynamics (LEHD) database on a set of metropolitan statistical areas (MSAs) with substantial immigrant populations, we find that, on average, 37% of an immigrant’s coworkers are themselves immigrants; in contrast, only 14% of a native-born worker’s coworkers are immigrants. We decompose this difference into the probability of working with compatriots versus with immigrants from other source countries. Using human capital, employer, and location characteristics, we narrow the mechanisms that might explain immigrant concentration. We find that industry, language, and residential segregation collectively explain almost all the excess tendency to work with immigrants from other source countries, but they have limited power to explain work with compatriots. This large unexplained compatriot component suggests an important role for unmeasured country-specific factors, such as social networks. PMID:25425452

  8. Micronuclei induced by municipal landfill leachate in mouse bone marrow cells in vivo

    International Nuclear Information System (INIS)

    Li Guangke; Sang Nan; Zhao Youcai

    2004-01-01

    The induction of micronuclei (MN) in polychromatic erythrocytes (PCE) of mouse bone marrow by municipal landfill leachate was studied in vivo. Results showed that mouse exposure via drinking water containing various concentrations of leachate caused a significant increase of MN frequencies in a concentration (Chemical oxygen demand measured with potassium dichromate oxidation, COD Cr )-dependent manner. MN induction in female and male mice was different at higher concentrations. This implies that leachate is a genotoxic agent in mammalian cells and that exposure to leachate in an aquatic environment may pose a potential genotoxic risk to human beings

  9. Mechanical properties of porcine brain tissue in vivo and ex vivo estimated by MR elastography.

    Science.gov (United States)

    Guertler, Charlotte A; Okamoto, Ruth J; Schmidt, John L; Badachhape, Andrew A; Johnson, Curtis L; Bayly, Philip V

    2018-03-01

    The mechanical properties of brain tissue in vivo determine the response of the brain to rapid skull acceleration. These properties are thus of great interest to the developers of mathematical models of traumatic brain injury (TBI) or neurosurgical simulations. Animal models provide valuable insight that can improve TBI modeling. In this study we compare estimates of mechanical properties of the Yucatan mini-pig brain in vivo and ex vivo using magnetic resonance elastography (MRE) at multiple frequencies. MRE allows estimations of properties in soft tissue, either in vivo or ex vivo, by imaging harmonic shear wave propagation. Most direct measurements of brain mechanical properties have been performed using samples of brain tissue ex vivo. It has been observed that direct estimates of brain mechanical properties depend on the frequency and amplitude of loading, as well as the time post-mortem and condition of the sample. Using MRE in the same animals at overlapping frequencies, we observe that porcine brain tissue in vivo appears stiffer than porcine brain tissue samples ex vivo at frequencies of 100 Hz and 125 Hz, but measurements show closer agreement at lower frequencies. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. In-vivo optical investigation of psoriasis

    Science.gov (United States)

    Kapsokalyvas, Dimitrios; Cicchi, Riccardo; Bruscino, Nicola; Alfieri, Domenico; Massi, Daniela; Lotti, Torello; Pavone, Francesco S.

    2011-03-01

    Psoriasis is an autoimmune disease of the skin characterized by hyperkeratosis, hyperproliferation of the epidermis, inflammatory cell accumulation and increased dilatation of dermal papillary blood vessels. Cases of psoriasis were investigated in vivo with optical means in order to evaluate the potential of in vivo optical biopsy. A Polarization Multispectral Dermoscope was employed for the macroscopic observation. Features such as the 'dotted' blood vessels pattern was observed with high contrast. The average size of dot vessels in Psoriasis was measured to be 974 μm2 which is much higher compared to healthy skin. High resolution image sections of the epidermis and the dermis were produced with a custom made Multiphoton Microscope. Imaging extended from the surface of the lesion down to the papillary dermis, at a depth of 200 μm. In the epidermis, a characteristic morphology of the stratum corneum found only in Psoriasis was revealed. Additionally, the cytoplasmic area of the cells in the stratum spinosum layer was found to be smaller than normal. In the dermis the morphological features were more pronounced, where the elongated dermal papillae dominated the papillary layer. Their length exceeds 100μm, which is a far greater value compared to that of healthy skin. These in vivo observations are consistent with the ex vivo histopathological observations, supporting both the applicability and potentiality of multispectral dermoscopy and multiphoton microscopy in the field of in vivo optical investigation and biopsy of skin.

  11. OpenVIVO: Transparency in Scholarship

    Directory of Open Access Journals (Sweden)

    Violeta Ilik

    2018-03-01

    Full Text Available OpenVIVO is a free and open-hosted semantic web platform that anyone can join and that gathers and shares open data about scholarship in the world. OpenVIVO, based on the VIVO open-source platform, provides transparent access to data about the scholarly work of its participants. OpenVIVO demonstrates the use of persistent identifiers, the automatic real-time ingest of scholarly ecosystem metadata, the use of VIVO-ISF and related ontologies, the attribution of work, and the publication and reuse of data—all critical components of presenting, preserving, and tracking scholarship. The system was created by a cross-institutional team over the course of 3 months. The team created and used RDF models for research organizations in the world based on Digital Science GRID data, for academic journals based on data from CrossRef and the US National Library of Medicine, and created a new model for attribution of scholarly work. All models, data, and software are available in open repositories.

  12. Brain intra- and extracellular sodium concentration in multiple sclerosis: a 7 T MRI study.

    Science.gov (United States)

    Petracca, Maria; Vancea, Roxana O; Fleysher, Lazar; Jonkman, Laura E; Oesingmann, Niels; Inglese, Matilde

    2016-03-01

    Intra-axonal accumulation of sodium ions is one of the key mechanisms of delayed neuro-axonal degeneration that contributes to disability accrual in multiple sclerosis. In vivo sodium magnetic resonance imaging studies have demonstrated an increase of brain total sodium concentration in patients with multiple sclerosis, especially in patients with greater disability. However, total sodium concentration is a weighted average of intra- and extra-cellular sodium concentration whose changes reflect different tissue pathophysiological processes. The in vivo, non-invasive measurement of intracellular sodium concentration is quite challenging and the few applications in patients with neurological diseases are limited to case reports and qualitative assessments. In the present study we provide first evidence of the feasibility of triple quantum filtered (23)Na magnetic resonance imaging at 7 T, and provide in vivo quantification of global and regional brain intra- and extra-cellular sodium concentration in 19 relapsing-remitting multiple sclerosis patients and 17 heathy controls. Global grey matter and white matter total sodium concentration (respectively P brain regional level, clusters of increased total sodium concentration and intracellular sodium concentration and decreased intracellular sodium volume fraction were found in several cortical, subcortical and white matter regions when patients were compared with healthy controls (P Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Application of quantitative autoradiography to the measurement of biochemical processes in vivo

    International Nuclear Information System (INIS)

    Sokoloff, L.

    1985-01-01

    Quantitative autoradiography makes it possible to measure the concentrations of isotopes in tissues of animals labeled in vivo. In a few cases, the administration of a judiciously selected labeled chemical compound and a properly designed procedure has made it possible to use this capability to measure the rate of a chemical process in animals in vivo. Emission tomography, and particularly positron emission tomography, provides a means to extend this capability to man and to assay the rates of biochemical processes in human tissues in vivo. It does not, however, obviate the need to adhere to established principles of chemical and enzyme kinetics and tracer theory. Generally, all such methods, whether to be used in man with positron emission tomography or in animals with autoradiography, must first be developed by research in animals with autoradiography, because it is only in animals that the measurements needed to validate the basic assumptions of the methods can be tested and evaluated

  14. In vitro and in vivo therapeutic activity of ibuprofen against dermatophytes

    International Nuclear Information System (INIS)

    AlJanabi, Ali S

    2009-01-01

    To evaluate the in vitro and in vivo therapeutic activity of ibuprofen against dermatophytes. The period of study ranged from June to September 2008. For in vitro investigation of ibuprofen activity, measurement of colony diameter, and dry weight were employed against 4 isolated strains of dermatophytes from 46 patients (30-43 years) suffering from dermatophytoses at Morgan Hospital, Hilla City, Iraq in June 2008. For the in vivo evaluation of ibuprofen, rabbits as the main subjects, were infected with dermatophytes and treated with prepared ibuprofen cream (15mg/gm). In vitro application of ibuprofen showed cidal activity on 4 strains of dermatophytes at minimum inhibitory concentrations of 200 ug/ml. The infected rabbits were successfully cured of dermatophytoses after treatment with ibuprofen cream. Based on in vitro and in vivo application, Ibuprofen can be used as a short-term cure for dermatophytoses. (author)

  15. SV40 Assembly In Vivo and In Vitro

    Directory of Open Access Journals (Sweden)

    Ariella Oppenheim

    2008-01-01

    Full Text Available The Simian virus 40 (SV40 capsid is a T = 7d icosahedral lattice ∼45 nm in diameter surrounding the ∼5 kb circular minichromosome. The outer shell is composed of 360 monomers of the major capsid protein VP1, tightly bound in 72 pentamers. VP1 is a jellyroll β-barrel, with extending N- and C-terminal arms. The N-terminal arms bind DNA and face the interior of the capsid. The flexible C-arms tie together the 72 pentamers in three distinct kinds of interactions, thus facilitating the formation of a T = 7 icosahedron from identical pentameric building blocks. Assembly in vivo was shown to occur by addition of capsomers around the DNA. We apply a combination of biochemical and genetic approaches to study SV40 assembly. Our in vivo and in vitro studies suggest the following model: one or two capsomers bind at a high affinity to ses, the viral DNA encapsidation signal, forming the nucleation centre for assembly. Next, multiple capsomers attach concomitantly, at lower affinity, around the minichromosome. This increases their local concentration facilitating rapid, cooperative assembly reaction. Formation of the icosahedron proceeds either by gradual addition of single pentamers to the growing shell or by concerted assembly of pentamer clusters.

  16. In vivo metabolite-specific imaging in tumor

    International Nuclear Information System (INIS)

    Hurd, R.E.; Freeman, D.M.

    1988-01-01

    The authors have developed a practical method using proton MR imaging to map the level and distribution of metabolites in vivo. Of particular interest to the biochemist and the clinician is the presence of excess lactic acid in tissues, indicating hypoxia such as is found in certain solid tumors, or in ischemia that would occur during cardiac infarct or stroke. A two-dimensional double quantum coherence technique has been optimized to greatly reduce signal intensity from biologic water and to provide unambiguous editing of the lactic acid resonance from interfering lipid resonances. The method was tested using a General Electric 2.0-T CSI instrument fitted with actively shielded gradients. Two-dimensional double quantum coherence lactic acid edited images were obtained from an implanted RIF-1 tumor in C3H mice, showing heterogeneous distribution of lactic acid within the tumor. Very little lipid signal with respect to the lactic acid methyl resonance was observed. The lactic acid concentration of the tumor was determined to be 10 μmol/g wet by enzymatic assay. Metabolite-specific imaging using double quantum coherence transfer promises to yield noninvasive information about lactic acid levels and distribution in vivo at low field, relatively quickly, with low radio frequency power disposition and without the need for complex presaturation pulses

  17. Aspartame induces angiogenesis in vitro and in vivo models.

    Science.gov (United States)

    Yesildal, F; Aydin, F N; Deveci, S; Tekin, S; Aydin, I; Mammadov, R; Fermanli, O; Avcu, F; Acikel, C H; Ozgurtas, T

    2015-03-01

    Angiogenesis is the process of generating new blood vessels from preexisting vessels and is considered essential in many pathological conditions. The purpose of the present study is to evaluate the effect of aspartame on angiogenesis in vivo chick chorioallantoic membrane (CAM) and wound-healing models as well as in vitro 2,3-bis-2H-tetrazolium-5-carboxanilide (XTT) and tube formation assays. In CAM assay, aspartame increased angiogenesis in a concentration-dependent manner. Compared with the control group, aspartame has significantly increased vessel proliferation (p aspartame group had better healing than control group, and this was statistically significant at p aspartame on human umbilical vein endothelial cells on XTT assay in vitro, but it was not statistically significant; and there was no antiangiogenic effect of aspartame on tube formation assay in vitro. These results provide evidence that aspartame induces angiogenesis in vitro and in vivo; so regular use may have undesirable effect on susceptible cases. © The Author(s) 2015.

  18. Conical electromagnetic radiation flux concentrator

    Science.gov (United States)

    Miller, E. R.

    1972-01-01

    Concentrator provides method of concentrating a beam of electromagnetic radiation into a smaller beam, presenting a higher flux density. Smaller beam may be made larger by sending radiation through the device in the reverse direction.

  19. Membrane distillation for milk concentration

    NARCIS (Netherlands)

    Moejes, S.N.; Romero Guzman, Maria; Hanemaaijer, J.H.; Barrera, K.H.; Feenstra, L.; Boxtel, van A.J.B.

    2015-01-01

    Membrane distillation is an emerging technology to concentrate liquid products while producing high quality water as permeate. Application for desalination has been studied extensively the past years, but membrane distillation has also potential to produce concentrated food products like

  20. In vivo cell tracking with bioluminescence imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jung Eun; Kalimuthu, Senthilkumar; Ahn, Byeong Cheol [Dept. of Nuclear Medicine, Kyungpook National University School of Medicine and Hospital, Daegu (Korea, Republic of)

    2015-03-15

    Molecular imaging is a fast growing biomedical research that allows the visual representation, characterization and quantification of biological processes at the cellular and subcellular levels within intact living organisms. In vivo tracking of cells is an indispensable technology for development and optimization of cell therapy for replacement or renewal of damaged or diseased tissue using transplanted cells, often autologous cells. With outstanding advantages of bioluminescence imaging, the imaging approach is most commonly applied for in vivo monitoring of transplanted stem cells or immune cells in order to assess viability of administered cells with therapeutic efficacy in preclinical small animal models. In this review, a general overview of bioluminescence is provided and recent updates of in vivo cell tracking using the bioluminescence signal are discussed.

  1. In Vivo Production of Entomopathogenic Nematodes.

    Science.gov (United States)

    Shapiro-Ilan, David I; Morales-Ramos, Juan A; Rojas, M Guadalupe

    2016-01-01

    In nature, entomopathogenic nematodes in the genera Heterorhabditis and Steinernema are obligate parasites of insects. The nematodes are used widely as biopesticides for suppression of insect pests. More than a dozen entomopathogenic nematode species have been commercialized for use in biological control. Most nematodes intended for commercial application are produced in artificial media via solid or liquid fermentation. However, for laboratory research and small greenhouse or field trials, in vivo production of entomopathogenic nematodes is the common method of propagation. Additionally, small companies continue to produce nematodes using in vivo methods for application in niche markets. Advances in mechanization and alternative production routes (e.g., production geared toward application of nematodes in infected host cadavers) can improve efficiency and economy of scale. The objective of this chapter is to describe basic and advanced procedures for in vivo production of entomopathogenic nematodes.

  2. Essential oils to control Botrytis cinerea in vitro and in vivo on plum fruits.

    Science.gov (United States)

    Aminifard, Mohammad Hossein; Mohammadi, Samane

    2013-01-01

    The consequence of misusing chemical biocides in controlling pests and diseases has drawn the attention of policy makers to the development of methods potentially available in nature for this purpose. In the present study the inhibitory effects of black caraway, fennel and peppermint essential oils against Botrytis cinerea were tested at various concentrations in vitro and in vivo. The in vitro results showed that the growth of B. cinerea was completely inhibited by the application of black caraway and fennel oils at concentrations of 400 and 600 µL L⁻¹ respectively. The in vivo results indicated that black caraway, fennel and peppermint oils at all applied concentrations inhibited B. cinerea growth on plum fruits compared with the control. In addition, all three oils at higher concentrations showed positive effects on fruit quality characteristics such as titrable acidity, total soluble solids, carbohydrate content, pH and weight loss percentage. Thus the oils inhibited the infection of plum fruits by B. cinerea and increased their storage life. This research confirms the antifungal effects of black caraway, fennel and peppermint essential oils both in vitro and in vivo on plum fruits postharvest. Therefore these essential oils could be an alternative to chemicals to control postharvest phytopathogenic fungi on plum fruits. Copyright © 2012 Society of Chemical Industry.

  3. Carprofen pharmacokinetics in plasma and in control and inflamed canine tissue fluid using in vivo ultrafiltration.

    Science.gov (United States)

    Messenger, K M; Wofford, J A; Papich, M G

    2016-02-01

    Measurement of unbound drug concentrations at their sites of action is necessary for accurate PK/PD modeling. The objective of this study was to determine the unbound concentration of carprofen in canine interstitial fluid (ISF) using in vivo ultrafiltration and to compare pharmacokinetic parameters of free carprofen concentrations between inflamed and control tissue sites. We hypothesized that active concentrations of carprofen would exhibit different dispositions in ISF between inflamed vs. normal tissues. Bilateral ultrafiltration probes were placed subcutaneously in six healthy Beagle dogs 12 h prior to induction of inflammation. Two milliliters of either 2% carrageenan or saline control was injected subcutaneously at each probe site, 12 h prior to intravenous carprofen (4 mg/kg) administration. Plasma and ISF samples were collected at regular intervals for 72 h, and carprofen concentrations were determined using HPLC. Prostaglandin E2 (PGE2 ) concentrations were quantified in ISF using ELISA. Unbound carprofen concentrations were higher in ISF compared with predicted unbound plasma drug concentrations. Concentrations were not significantly higher in inflamed ISF compared with control ISF. Compartmental modeling was used to generate pharmacokinetic parameter estimates, which were not significantly different between sites. Terminal half-life (T½) was longer in the ISF compared with plasma. PGE2 in ISF decreased following administration of carprofen. In vivo ultrafiltration is a reliable method to determine unbound carprofen in ISF, and that disposition of unbound drug into tissue is much higher than predicted from unbound drug concentration in plasma. However, concentrations and pharmacokinetic parameter estimates are not significantly different in inflamed vs. un-inflamed tissues. © 2015 John Wiley & Sons Ltd.

  4. Preparation and In Vivo Pharmacokinetics of the Tongshu Suppository

    Directory of Open Access Journals (Sweden)

    Guoqiang Liu

    2016-01-01

    Full Text Available Astragalus polysaccharide (APS (used for intestinal protection was added to formulate the Tongshu suppository to improve the pharmacokinetics of Aceclofenac, which were assessed in New Zealand rabbits using an orthogonal experimental design. The single-agent Aceclofenac was taken as the control formulation. The concentration-time and drug release curves were drawn, and Tmax (min, Cmax (μg·mL−1, AUC0→∞, and MRT were compared using a pharmacokinetic systems program. The formulated Tongshu suppository had moderate hardness, a smooth surface with uniform color, and theoretical drug-loading rate of 8%. Its release rate was in accordance with the drug preparation requirements. The concentration-time curves and drug release curves revealed that the maximum concentrations (Cmax were 4.18±1.03 μg·mL−1 and 3.34±0.41 μg·mL−1 for the Tongshu and Aceclofenac suppositories, respectively, showing statistically insignificant difference, while the peak times were 34.87±4.69 min and 34.76±6.34 min, respectively, also showing statistically insignificant difference. Compared with the Aceclofenac suppository, the relative bioavailability of the Tongshu suppository was 104.4%, and the difference between them was statistically insignificant. In this experiment, the Tongshu suppository was prepared using the hot-melt method. In vivo pharmacokinetic studies confirmed it had higher bioavailability than the Aceclofenac suppository.

  5. Preparation and In Vivo Pharmacokinetics of the Tongshu Suppository

    Science.gov (United States)

    Dong, Leilei; Lu, Kuan; Liu, Sisi; Zheng, Yingying

    2016-01-01

    Astragalus polysaccharide (APS) (used for intestinal protection) was added to formulate the Tongshu suppository to improve the pharmacokinetics of Aceclofenac, which were assessed in New Zealand rabbits using an orthogonal experimental design. The single-agent Aceclofenac was taken as the control formulation. The concentration-time and drug release curves were drawn, and T max (min), C max (μg·mL−1), AUC0→∞, and MRT were compared using a pharmacokinetic systems program. The formulated Tongshu suppository had moderate hardness, a smooth surface with uniform color, and theoretical drug-loading rate of 8%. Its release rate was in accordance with the drug preparation requirements. The concentration-time curves and drug release curves revealed that the maximum concentrations (C max) were 4.18 ± 1.03 μg·mL−1 and 3.34 ± 0.41 μg·mL−1 for the Tongshu and Aceclofenac suppositories, respectively, showing statistically insignificant difference, while the peak times were 34.87 ± 4.69 min and 34.76 ± 6.34 min, respectively, also showing statistically insignificant difference. Compared with the Aceclofenac suppository, the relative bioavailability of the Tongshu suppository was 104.4%, and the difference between them was statistically insignificant. In this experiment, the Tongshu suppository was prepared using the hot-melt method. In vivo pharmacokinetic studies confirmed it had higher bioavailability than the Aceclofenac suppository. PMID:27610366

  6. Investigations on renal organic and inorganic solutes, in vivo

    International Nuclear Information System (INIS)

    Wolff, S.D.

    1989-01-01

    A basic question in renal physiology is how do the cells of the renal medulla survive the high concentrations of sodium chloride and urea which occur with antidiuresis. The problem is two-fold: (1) urea, being highly permeable to cell membranes, should enter the cell and adversely affect protein function; and (2) inorganic ions, being in much higher concentration extracellularly than intracellularly should dehydrate the cell. If these organic solutes exist in response to high concentrations of sodium chloride and urea, then their content should vary with diuretic state. Two protocols were developed to test the validity of this hypothesis. The first protocol used 31 P-NMR in vivo to monitor GPC content before, during, and after acute diuresis in an exteriorized rabbit kidney model. Changes in sodium distribution and tissue structure were monitored dynamically with 23 Na- and 1 H-NMR imaging, respectively. The second protocol used HPLC to quantitate each of the four organic solutes in renal inner medullary homogenates. Here, the effect of diuretic state and acute diuresis on organic solute content was assessed

  7. In vivo virtual intraoperative surgical photoacoustic microscopy

    International Nuclear Information System (INIS)

    Han, Seunghoon; Kim, Sehui; Kim, Jeehyun; Lee, Changho; Jeon, Mansik; Kim, Chulhong

    2013-01-01

    We developed a virtual intraoperative surgical photoacoustic microscopy system by combining with a commercial surgical microscope and photoacoustic microscope (PAM). By sharing the common optical path in the microscope and PAM system, we could acquire the PAM and microscope images simultaneously. Moreover, by employing a beam projector to back-project 2D PAM images onto the microscope view plane as augmented reality, the conventional microscopic and 2D cross-sectional PAM images are concurrently mapped on the plane via an ocular lens of the microscope in real-time. Further, we guided needle insertion into phantom ex vivo and mice skins in vivo

  8. In vivo virtual intraoperative surgical photoacoustic microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seunghoon, E-mail: hsh860504@gmail.com; Kim, Sehui, E-mail: sehui0916@nate.com; Kim, Jeehyun, E-mail: jeehk@knu.ac.kr, E-mail: chulhong@postech.edu [School of Electrical Engineering and Computer Science, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Lee, Changho, E-mail: ch31037@postech.edu; Jeon, Mansik, E-mail: msjeon@postech.edu [Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of); Kim, Chulhong, E-mail: jeehk@knu.ac.kr, E-mail: chulhong@postech.edu [Department of Creative IT Engineering, Pohang University of Science and Technology (POSTECH), Pohang 790-784 (Korea, Republic of); Department of Biomedical Engineering, The State University of New York at Buffalo, Buffalo, New York 14221 (United States)

    2013-11-11

    We developed a virtual intraoperative surgical photoacoustic microscopy system by combining with a commercial surgical microscope and photoacoustic microscope (PAM). By sharing the common optical path in the microscope and PAM system, we could acquire the PAM and microscope images simultaneously. Moreover, by employing a beam projector to back-project 2D PAM images onto the microscope view plane as augmented reality, the conventional microscopic and 2D cross-sectional PAM images are concurrently mapped on the plane via an ocular lens of the microscope in real-time. Further, we guided needle insertion into phantom ex vivo and mice skins in vivo.

  9. Noninvasive control of rhodamine-loaded capsules distribution in vivo

    Science.gov (United States)

    Stelmashchuk, O.; Tarakanchikova, Y.; Seryogina, E.; Piavchenko, G.; Zherebtsov, E.; Dunaev, A.; Popov, A.; Meglinski, I.

    2018-04-01

    Using fluorescence spectroscopy system with fibre-optical probe, we investigated the dynamics of propagation and circulation in the microcirculatory system of experimental nanocapsules fluorescent-labelled (rhodamine TRITC) nanocapsules. The studies were carried out in clinically healthy Wistar rats. The model animals were divided into control group and group received injections of the nanocapsules. The fluorescent measurements conducted transcutaneously on the thigh surface. The administration of the preparation with the rhodamine concentration of 5 mg/kg of animal weight resulted in twofold increase of fluorescence intensity by reference to the baseline level. As a result of the study, it was concluded that fluorescence spectroscopy can be used for transdermal measurements of the rhodamine-loaded capsules in vivo.

  10. A dynamic model for in vivo virus replication

    Energy Technology Data Exchange (ETDEWEB)

    MacCarthy, J.E.; Kozak, J.J.

    1980-01-01

    In this paper a dynamic model of in vivo virus replication is presented. Kinetic equations are formulated to describe the overall process of replication and then analyzed using a ''synergetic'' approach. First the importance of a rate-limiting substrate is taken explicitly into account, and secondly the coupling between the processes considered (translation, replication and assembly) is strictly preserved; the analysis itself is carried out in the linear regime. The problems of defective-particle infections, standard-virus infections, inhibition of cellular synthesis, and the case of co-infected cells are treated. The various parameters of the model (initial cellular concentrations, rate constants) are specified using existing experimental data and the full (numerical) consequences of the model are explored in detail. The simple model developed is able to account qualitatively, and occasionally quantitatively, for the behavior observed experimentally for each of the problems cited above.

  11. In vivo studies of peritendinous tissue in exercise

    DEFF Research Database (Denmark)

    Kjaer, M; Langberg, Henning; Skovgaard, D

    2000-01-01

    Soft tissue injury of tendons represents a major problem within sports medicine. Although several animal and cell culture studies have addressed this, human experiments have been limited in their ability to follow changes in specific tissue directly in response to interventions. Recently, methods...... have allowed for in vivo determination of tissue concentrations and release rates of substances involved in metabolism, inflammation and collagen synthesis, together with the measurement of tissue blood flow and oxygenation in the peritendinous region around the Achilles tendon in humans during...... exercise. This coincides with a surprisingly marked drop in tissue pressure during contraction. With regards to both circulation, metabolism and collagen formation, peritendinous tissue represents a dynamic, responsive region that adapts markedly to acute muscular activity....

  12. In vivo MRS metabolite quantification using genetic optimization

    Science.gov (United States)

    Papakostas, G. A.; Karras, D. A.; Mertzios, B. G.; van Ormondt, D.; Graveron-Demilly, D.

    2011-11-01

    The in vivo quantification of metabolites' concentrations, revealed in magnetic resonance spectroscopy (MRS) spectra, constitutes the main subject under investigation in this work. Significant contributions based on artificial intelligence tools, such as neural networks (NNs), with good results have been presented lately but have shown several drawbacks, regarding their quantification accuracy under difficult conditions. A general framework that encounters the quantification procedure as an optimization problem, which is solved using a genetic algorithm (GA), is proposed in this paper. Two different lineshape models are examined, while two GA configurations are applied on artificial data. Moreover, the introduced quantification technique deals with metabolite peaks' overlapping, a considerably difficult situation occurring under real conditions. Appropriate experiments have proved the efficiency of the introduced methodology, in artificial MRS data, by establishing it as a generic metabolite quantification procedure.

  13. In vivo MRS metabolite quantification using genetic optimization

    International Nuclear Information System (INIS)

    Papakostas, G A; Mertzios, B G; Karras, D A; Van Ormondt, D; Graveron-Demilly, D

    2011-01-01

    The in vivo quantification of metabolites' concentrations, revealed in magnetic resonance spectroscopy (MRS) spectra, constitutes the main subject under investigation in this work. Significant contributions based on artificial intelligence tools, such as neural networks (NNs), with good results have been presented lately but have shown several drawbacks, regarding their quantification accuracy under difficult conditions. A general framework that encounters the quantification procedure as an optimization problem, which is solved using a genetic algorithm (GA), is proposed in this paper. Two different lineshape models are examined, while two GA configurations are applied on artificial data. Moreover, the introduced quantification technique deals with metabolite peaks' overlapping, a considerably difficult situation occurring under real conditions. Appropriate experiments have proved the efficiency of the introduced methodology, in artificial MRS data, by establishing it as a generic metabolite quantification procedure

  14. A Microfluidic Ion Pump for In Vivo Drug Delivery

    KAUST Repository

    Uguz, Ilke

    2017-05-15

    Implantable devices offer an alternative to systemic delivery of drugs for the treatment of neurological disorders. A microfluidic ion pump (µFIP), capable of delivering a drug without the solvent through electrophoresis, is developed. The device is characterized in vitro by delivering γ-amino butyric acid to a target solution, and demonstrates low-voltage operation, high drug-delivery capacity, and high ON/OFF ratio. It is also demonstrated that the device is suitable for cortical delivery in vivo by manipulating the local ion concentration in an animal model and altering neural behavior. These results show that µFIPs represent a significant step forward toward the development of implantable drug-delivery systems.

  15. Chitosan coated carbon fiber microelectrode for selective in vivo detection of neurotransmitters in live zebrafish embryos

    International Nuclear Information System (INIS)

    Ozel, Rifat Emrah; Wallace, Kenneth N.; Andreescu, Silvana

    2011-01-01

    Graphical abstract: Chitosan coated fiber electrodes are sensitive to serotonin detection while rejecting physiological levels of ascorbic acid interferences. - Abstract: We report the development of a chitosan modified carbon fiber microelectrode for in vivo detection of serotonin. We find that chitosan has the ability to reject physiological levels of ascorbic acid interferences and facilitate selective and sensitive detection of in vivo levels of serotonin, a common catecholamine neurotransmitter. Presence of chitosan on the microelectrode surface was investigated using scanning electron microscopy (SEM) and cyclic voltammetry (CV). The electrode was characterized using differential pulse voltammetry (DPV). A detection limit of 1.6 nM serotonin with a sensitivity of 5.12 nA/μM, a linear range from 2 to 100 nM and a reproducibility of 6.5% for n = 6 electrodes were obtained. Chitosan modified microelectrodes selectively measure serotonin in presence of physiological levels of ascorbic acid. In vivo measurements were performed to measure concentration of serotonin in the live embryonic zebrafish intestine. The sensor quantifies in vivo intestinal levels of serotonin while successfully rejecting ascorbic acid interferences. We demonstrate that chitosan can be used as an effective coating to reject ascorbic acid interferences at carbon fiber microelectrodes, as an alternative to Nafion, and that chitosan modified microelectrodes are reliable tools for in vivo monitoring of changes in neurotransmitter levels.

  16. Chitosan coated carbon fiber microelectrode for selective in vivo detection of neurotransmitters in live zebrafish embryos

    Energy Technology Data Exchange (ETDEWEB)

    Ozel, Rifat Emrah [Department of Chemistry and Biomolecular Science, 8 Clarkson Ave, Potsdam, NY 136995810 (United States); Wallace, Kenneth N. [Department of Biology, Clarkson University, Potsdam, NY 136995810 (United States); Andreescu, Silvana, E-mail: eandrees@clarkson.edu [Department of Chemistry and Biomolecular Science, 8 Clarkson Ave, Potsdam, NY 136995810 (United States)

    2011-06-10

    Graphical abstract: Chitosan coated fiber electrodes are sensitive to serotonin detection while rejecting physiological levels of ascorbic acid interferences. - Abstract: We report the development of a chitosan modified carbon fiber microelectrode for in vivo detection of serotonin. We find that chitosan has the ability to reject physiological levels of ascorbic acid interferences and facilitate selective and sensitive detection of in vivo levels of serotonin, a common catecholamine neurotransmitter. Presence of chitosan on the microelectrode surface was investigated using scanning electron microscopy (SEM) and cyclic voltammetry (CV). The electrode was characterized using differential pulse voltammetry (DPV). A detection limit of 1.6 nM serotonin with a sensitivity of 5.12 nA/{mu}M, a linear range from 2 to 100 nM and a reproducibility of 6.5% for n = 6 electrodes were obtained. Chitosan modified microelectrodes selectively measure serotonin in presence of physiological levels of ascorbic acid. In vivo measurements were performed to measure concentration of serotonin in the live embryonic zebrafish intestine. The sensor quantifies in vivo intestinal levels of serotonin while successfully rejecting ascorbic acid interferences. We demonstrate that chitosan can be used as an effective coating to reject ascorbic acid interferences at carbon fiber microelectrodes, as an alternative to Nafion, and that chitosan modified microelectrodes are reliable tools for in vivo monitoring of changes in neurotransmitter levels.

  17. Influence of drug concentration on the diffusion parameters of caffeine

    Science.gov (United States)

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

    2011-01-01

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

  18. In vitro and in vivo antioxidant activity of the pulp of Jatobá-do-cerrado

    Directory of Open Access Journals (Sweden)

    Daniela Granja ARAKAKI

    2016-03-01

    Full Text Available Abstract Oxygen metabolism in cells causes the production of free radicals, which produce damage, including changes in cell structure and function. Antioxidants are substances that, at low concentrations, slow down or prevent oxidation. Fruits and vegetables contribute to the dietary supply of these compounds. The flora of the Cerrado in Brazil has shown to have high levels of bioactive compounds. This study aimed to characterize the antioxidant activity of the pulp of jatobá-do-cerrado in vitro and in vivo.In vitro antioxidant activity of the aqueous, ethanol and aqueous acetone extracts was evaluated by the DPPH method. We determined total phenols by the Folin-Ciocalteu assay and tannins by the Folin-Denis method.In vivo antioxidant potential of the aqueous acetone extract was evaluated by the TBARS technique. The aqueous acetone extract had the highest antioxidant capacity, followed by the aqueous and ethanol extracts. The same pattern occurred in the extraction of phenols and in the extraction of tannins. In vivo administration of the aqueous acetone extract inhibited lipid peroxidation compared to the control group. The inhibition of peroxidation has increased by elevating the dosage concentration of the extracts, demonstrating a significant antioxidant potential in vivo as well as in vitro.

  19. Responses of Soybean Mutant Lines to Aluminium under In Vitro and In Vivo Condition

    International Nuclear Information System (INIS)

    Yuliasti; Sudarsono

    2011-01-01

    The main limited factors of soybean plants expansion in acid soil are Aluminium (Al) toxicity and low pH. The best approach to solve this problem is by using Al tolerance variety. In vitro or in vivo selections using selective media containing AlCl 3 and induced callus embryonic of mutant lines are reliable methods to develop a new variety. The objectives of this research are to evaluate response of soybean genotypes against AlCl 3 under in vitro and in vivo condition. Addition of 15 part per million (ppm) AlCl 3 into in vitro and in vivo media severely affected plant growth. G3 soybean mutant line was identified as more tolerant than the control soybean cultivar Tanggamus. This mutant line was able to survive under more severe AlCl 3 concentrations (15 ppm) under in vitro conditions. Under in vivo conditions, G1 and G4 mutants were also identified as more tolerant than Tanggamus since they produced more pods and higher dry seed weigh per plant. Moreover, G4 mutant line also produced more dry seed weight per plant than Tanggamus when they were grown on soil containing high Al concentration 8.1 me/100 gr = 81 ppm Al +3 . (author)

  20. Concentrating on caustic

    International Nuclear Information System (INIS)

    Collins, Richard

    2010-01-01

    Full text: First there was the Beer Battery, which aimed to generate electricity from brewery wastewater using a microbial fuel cell (MFC). Trials at Foster's Yatala brewery in Queensland in 2007 ran into challenges around the cost of electricity and duration of treatment, but they also revealed a new possibility. Komeel Rabaey, a University of Queensland specialist in microbial dynamics with a particular passion for bioelectrochemical systems, recognised the potential to extract sodium hydroxide - caustic soda - out of wastewater in a form suitable for reuse. In 2008 he converted such a system into a lab-scale caustic recovery plant, then upsized it to a one litre test reactor, which is again running at the Yatala brewery. The concept flips wastewater treatment on its head, seeing the discharge as a resource to be harvested rather than a cost and a contaminant load to be managed. “We typically aim to make a concentration of about four per cent caustic. That is what is easily achievable with the system and you will also note a lot of industries use caustic at four per cent,” said Dr Rabaey. “So you can use the wastewater from the plant to drive caustic production, with the extra advantage of removing enormous amounts of sodium.” Sodium hydroxide is a ubiquitous industrial compound used in pH regulation, as a cleaning agent in clean-in-place systems and variously in pulp and paper, textiles and food processing. Dr Rabaey wants to close the loop on caustic. Industries along the Murray-Darling basin, for example, truck in a lot of it from outside the area and then discharge it with their wastewater into the salt-sensitive river system. “If you use a bioelectrochemical system to recover the sodium hydroxide, you are not even importing the sodium into the area but recycling the sodium the whole time on-site,” he told WME. Get the technology right and he reckons a three-year payback on investment is readily achievable. A microbial fuel cell oxidises organics

  1. In vivo and ex vivo proton MR spectroscopy of primary and secondary melanoma

    Energy Technology Data Exchange (ETDEWEB)

    Bourne, Roger M.; Stanwell, Peter; Stretch, Jonathan R.; Scolyer, Richard A.; Thompson, John F.; Mountford, Carolyn E.; Lean, Cynthia L

    2005-03-01

    In vivo magnetic resonance (MR) spectroscopy at 1.5T was performed on a large polypoid cutaneous melanoma, and two enlarged lymph nodes containing metastatic melanoma, from three patients. Spectra were acquired in vivo from voxels wholly within the primary tumour or secondary lymph node and were thus uncontaminated by signals from adjacent tissue. Tissue biopsies taken after resection of primary tumours and secondary lymph nodes were examined by 8.5T magnetic resonance spectroscopy (MRS) and the results compared with the in vivo spectra, and with spectra from normal skin and a benign skin lesion. There was good agreement between the dominant features of 1.5T spectra acquired in vivo and 8.5T spectra acquired from resected tissue. However, less intense resonances observed at 8.5T in malignant biopsy tissue were not consistently observed at 1.5T in vivo. In vivo spectra from primary and metastatic melanoma showed high levels of choline metabolites. An intense lactate resonance was also present in the in vivo spectrum of primary melanoma. All 8.5T spectra of biopsies from primary and secondary melanoma showed high levels of choline metabolites and lactate, and additional resonances consistent with elevated levels of taurine, alanine, lysine, and glutamate/glutamine relative to normal and benign tissue. Elevated levels of choline, lactate, taurine, and amino acids appear to be clinically useful markers for identifying the pathology of primary and metastatic melanoma.

  2. Accurate determination of brain metabolite concentrations using ERETIC as external reference.

    Science.gov (United States)

    Zoelch, Niklaus; Hock, Andreas; Heinzer-Schweizer, Susanne; Avdievitch, Nikolai; Henning, Anke

    2017-08-01

    Magnetic Resonance Spectroscopy (MRS) can provide in vivo metabolite concentrations in standard concentration units if a reliable reference signal is available. For 1 H MRS in the human brain, typically the signal from the tissue water is used as the (internal) reference signal. However, a concentration determination based on the tissue water signal most often requires a reliable estimate of the water concentration present in the investigated tissue. Especially in clinically interesting cases, this estimation might be difficult. To avoid assumptions about the water in the investigated tissue, the Electric REference To access In vivo Concentrations (ERETIC) method has been proposed. In this approach, the metabolite signal is compared with a reference signal acquired in a phantom and potential coil-loading differences are corrected using a synthetic reference signal. The aim of this study, conducted with a transceiver quadrature head coil, was to increase the accuracy of the ERETIC method by correcting the influence of spatial B 1 inhomogeneities and to simplify the quantification with ERETIC by incorporating an automatic phase correction for the ERETIC signal. Transmit field ( B1+) differences are minimized with a volume-selective power optimization, whereas reception sensitivity changes are corrected using contrast-minimized images of the brain and by adapting the voxel location in the phantom measurement closely to the position measured in vivo. By applying the proposed B 1 correction scheme, the mean metabolite concentrations determined with ERETIC in 21 healthy subjects at three different positions agree with concentrations derived with the tissue water signal as reference. In addition, brain water concentrations determined with ERETIC were in agreement with estimations derived using tissue segmentation and literature values for relative water densities. Based on the results, the ERETIC method presented here is a valid tool to derive in vivo metabolite

  3. Ex-vivo MR Volumetry of Human Brain Hemispheres

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A.; Schneider, Julie A.; Dawe, Robert J.; Golak, Tom; Leurgans, Sue E.; Yu, Lei; Arfanakis, Konstantinos

    2013-01-01

    Purpose The aims of this work were to: a) develop an approach for ex-vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, b) longitudinally assess regional brain volumes postmortem, and c) investigate the relationship between MR volumetric measurements performed in-vivo and ex-vivo. Methods An approach for ex-vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex-vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex-vivo was assessed. The relationship between in-vivo and ex-vivo volumetric measurements was investigated in seven elderly subjects imaged both ante-mortem and postmortem. Results The presented approach for ex-vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than inter-subject volume variation. A close linear correspondence was detected between in-vivo and ex-vivo volumetric measurements. Conclusion Regional brain volumes measured with the presented approach for ex-vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in-vivo and ex-vivo MR volumetric measurements suggests that the presented approach captures information linked to ante-mortem macrostructural brain characteristics. PMID:23440751

  4. Ex vivo MR volumetry of human brain hemispheres.

    Science.gov (United States)

    Kotrotsou, Aikaterini; Bennett, David A; Schneider, Julie A; Dawe, Robert J; Golak, Tom; Leurgans, Sue E; Yu, Lei; Arfanakis, Konstantinos

    2014-01-01

    The aims of this work were to (a) develop an approach for ex vivo MR volumetry of human brain hemispheres that does not contaminate the results of histopathological examination, (b) longitudinally assess regional brain volumes postmortem, and (c) investigate the relationship between MR volumetric measurements performed in vivo and ex vivo. An approach for ex vivo MR volumetry of human brain hemispheres was developed. Five hemispheres from elderly subjects were imaged ex vivo longitudinally. All datasets were segmented. The longitudinal behavior of volumes measured ex vivo was assessed. The relationship between in vivo and ex vivo volumetric measurements was investigated in seven elderly subjects imaged both antemortem and postmortem. This approach for ex vivo MR volumetry did not contaminate the results of histopathological examination. For a period of 6 months postmortem, within-subject volume variation across time points was substantially smaller than intersubject volume variation. A close linear correspondence was detected between in vivo and ex vivo volumetric measurements. Regional brain volumes measured with this approach for ex vivo MR volumetry remain relatively unchanged for a period of 6 months postmortem. Furthermore, the linear relationship between in vivo and ex vivo MR volumetric measurements suggests that this approach captures information linked to antemortem macrostructural brain characteristics. Copyright © 2013 Wiley Periodicals, Inc.

  5. In vivo dosimetry in external beam radiotherapy

    International Nuclear Information System (INIS)

    Mijnheer, Ben; Beddar, Sam; Izewska, Joanna; Reft, Chester

    2013-01-01

    In vivo dosimetry (IVD) is in use in external beam radiotherapy (EBRT) to detect major errors, to assess clinically relevant differences between planned and delivered dose, to record dose received by individual patients, and to fulfill legal requirements. After discussing briefly the main characteristics of the most commonly applied IVD systems, the clinical experience of IVD during EBRT will be summarized. Advancement of the traditional aspects of in vivo dosimetry as well as the development of currently available and newly emerging noninterventional technologies are required for large-scale implementation of IVD in EBRT. These new technologies include the development of electronic portal imaging devices for 2D and 3D patient dosimetry during advanced treatment techniques, such as IMRT and VMAT, and the use of IVD in proton and ion radiotherapy by measuring the decay of radiation-induced radionuclides. In the final analysis, we will show in this Vision 20/20 paper that in addition to regulatory compliance and reimbursement issues, the rationale for in vivo measurements is to provide an accurate and independent verification of the overall treatment procedure. It will enable the identification of potential errors in dose calculation, data transfer, dose delivery, patient setup, and changes in patient anatomy. It is the authors’ opinion that all treatments with curative intent should be verified through in vivo dose measurements in combination with pretreatment checks

  6. Computational design of in vivo biomarkers

    International Nuclear Information System (INIS)

    Somogyi, Bálint; Gali, Adam

    2014-01-01

    Fluorescent semiconductor nanocrystals (or quantum dots) are very promising agents for bioimaging applications because their optical properties are superior compared to those of conventional organic dyes. However, not all the properties of these quantum dots suit the stringent criteria of in vivo applications, i.e. their employment in living organisms that might be of importance in therapy and medicine. In our review, we first summarize the properties of an ‘ideal’ biomarker needed for in vivo applications. Despite recent efforts, no such hand-made fluorescent quantum dot exists that may be considered as ‘ideal’ in this respect. We propose that ab initio atomistic simulations with predictive power can be used to design ‘ideal’ in vivo fluorescent semiconductor nanoparticles. We briefly review such ab initio methods that can be applied to calculate the electronic and optical properties of very small nanocrystals, with extra emphasis on density functional theory (DFT) and time-dependent DFT which are the most suitable approaches for the description of these systems. Finally, we present our recent results on this topic where we investigated the applicability of nanodiamonds and silicon carbide nanocrystals for in vivo bioimaging. (topical review)

  7. Ebola Virus Persistence in Semen Ex Vivo.

    Science.gov (United States)

    Fischer, Robert J; Judson, Seth; Miazgowicz, Kerri; Bushmaker, Trent; Munster, Vincent J

    2016-02-01

    On March 20, 2015, a case of Ebola virus disease was identified in Liberia that most likely was transmitted through sexual contact. We assessed the efficiency of detecting Ebola virus in semen samples by molecular diagnostics and the stability of Ebola virus in ex vivo semen under simulated tropical conditions.

  8. Miniature semiconductor detectors for in vivo dosimetry

    International Nuclear Information System (INIS)

    Rosenfeld, A. B.; Cutajar, D.; Lerch, M. L. F.; Takacs, G.; Cornelius, I. M.; Yudelev, M.; Zaider, M.

    2006-01-01

    Silicon mini-semiconductor detectors are found in wide applications for in vivo personal dosimetry and dosimetry and Micro-dosimetry of different radiation oncology modalities. These applications are based on integral and spectroscopy modes of metal oxide semiconductor field effect transistor and silicon p-n junction detectors. The advantages and limitations of each are discussed. (authors)

  9. In vivo dosimetry in external beam radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Mijnheer, Ben [Department of Radiation Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam 1066 CX (Netherlands); Beddar, Sam [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Izewska, Joanna [Division of Human Health, International Atomic Energy Agency, Vienna 1400 (Austria); Reft, Chester [Department of Radiation and Cellular Oncology, University of Chicago Medical Center, Chicago, Illinois 60637 (United States)

    2013-07-15

    In vivo dosimetry (IVD) is in use in external beam radiotherapy (EBRT) to detect major errors, to assess clinically relevant differences between planned and delivered dose, to record dose received by individual patients, and to fulfill legal requirements. After discussing briefly the main characteristics of the most commonly applied IVD systems, the clinical experience of IVD during EBRT will be summarized. Advancement of the traditional aspects of in vivo dosimetry as well as the development of currently available and newly emerging noninterventional technologies are required for large-scale implementation of IVD in EBRT. These new technologies include the development of electronic portal imaging devices for 2D and 3D patient dosimetry during advanced treatment techniques, such as IMRT and VMAT, and the use of IVD in proton and ion radiotherapy by measuring the decay of radiation-induced radionuclides. In the final analysis, we will show in this Vision 20/20 paper that in addition to regulatory compliance and reimbursement issues, the rationale for in vivo measurements is to provide an accurate and independent verification of the overall treatment procedure. It will enable the identification of potential errors in dose calculation, data transfer, dose delivery, patient setup, and changes in patient anatomy. It is the authors' opinion that all treatments with curative intent should be verified through in vivo dose measurements in combination with pretreatment checks.

  10. Muscle-Driven In Vivo Nanogenerator

    KAUST Repository

    Li, Zhou; Zhu, Guang; Yang, Rusen; Wang, Aurelia C.; Wang, Zhong Lin

    2010-01-01

    of such a nanogenerator in a live rat where it harvests energy generated by its breathing or heart beating. This study shows the potential of applying these nanogenerators for driving in vivo nanodevices. © 2010 WILEY-VCH Verlag GmbH & Co. KCaA, Weinheim.

  11. In vitro and in vivo studies of the endocrine disrupting potency of cadmium in roach (Rutilus rutilus) liver

    International Nuclear Information System (INIS)

    Gerbron, M.; Geraudie, P.; Xuereb, B.; Marie, S.; Minier, C.

    2015-01-01

    Highlights: • Ex vivo and in vivo experiments suggest estrogen receptor-driven effects of cadmium. • CdCl 2 is strongly anti-estrogenic when co-exposed to E2. • CdCl 2 + E2 significantly inhibit vtg and erα mRNA expressions. • CdCl 2 compromises the E2-mediated induction of the ar mRNA expression in vivo. - Abstract: Cadmium has been reported to exert estrogenic, antiestrogenic or both effects in vertebrate species. To elucidate the endocrine disrupting action of CdCl 2 , ex vivo and in vivo experiments were performed in roach (Rutilus rutilus). Roach liver explants were exposed to a range of CdCl 2 concentrations alone (0.1–50 μM) or with an effective concentration (100 nM) of 17β-estradiol (E2). In addition, juvenile roach were intraperitoneally injected with CdCl 2 (0.1–2.5 mg/kg) with or without 1 mg E2/kg. Subsequent analysis evaluated the effect of CdCl 2 on vitellogenin (VTG) synthesis both at the mRNA and protein level, on estrogen receptors (erα and erβ1) and on androgen receptor (ar) mRNA expression. Ex vivo and in vivo experiments indicated that CdCl 2 is strongly anti-estrogenic as, when co-exposed to E2, CdCl 2 significantly inhibited VTG production as well as vtg and erα mRNA expressions. Moreover, CdCl 2 compromised the E2-mediated induction of the ar mRNA expression in vivo

  12. [Ozone concentration distribution of urban].

    Science.gov (United States)

    Yin, Yong-quan; Li, Chang-mei; Ma, Gui-xia; Cui, Zhao-jie

    2004-11-01

    The increase of ozone concentration in urban is one of the most important research topics on environmental science. With the increase of nitrogen oxides and hydrogen-carbon compounds which are exhausted from cars, the ozone concentration in urban is obviously increased on sunlight, and threat of photochemistry smog will be possible. Therefore, it is very important to monitor and study the ozone concentration distribution in urban. The frequency-distribution, diurnal variation and monthly variation of ozone concentration were studied on the campus of Shandong University during six months monitoring. The influence of solar radiation and weather conditions on ozone concentration were discussed. The frequency of ozone concentration less than 200 microg/m3 is 96.88%. The ozone concentration has an obvious diurnal variation. The ozone concentration in the afternoon is higher than in the morning and in the evening. The maximum appears in June, when it is the strong solar radiation and high air-temperature. The weather conditions also influence the ozone concentration. The ozone concentration in clear day is higher than in rainy and cloudy day.

  13. Low concentrator PV optics optimization

    Science.gov (United States)

    Sharp, Leonard; Chang, Ben

    2008-08-01

    Purpose: Cost reduction is a major focus of the solar industry. Thin film technologies and concentration systems are viable ways to reducing cost, with unique strengths and weakness for both. Most of the concentrating PV work focuses on high concentration systems for reducing energy cost. Meanwhile, many believe that low concentrators provide significant cost reduction potential while addressing the mainstream PV market with a product that acts as a flat panel replacement. This paper analyzes the relative benefit of asymmetric vs. symmetric optics for low-concentrators in light of specific PV applications. Approach: Symmetric and asymmetric concentrating PV module performance is evaluated using computer simulation to determine potential value across various geographic locations and applications. The selected optic design is modeled against standard cSi flat panels and thin film to determine application fit, system level energy density and economic value. Results: While symmetric designs may seem ideal, asymmetric designs have an advantage in energy density. Both designs are assessed for aperture, optimum concentration ratio, and ideal system array configuration. Analysis of performance across climate specific effects (diffuse, direct and circumsolar) and location specific effects (sunpath) are also presented. The energy density and energy production of low concentrators provide a compelling value proposition. More significantly, the choice of optics for a low concentrating design can affect real world performance. With the goal of maximizing energy density and return on investment, this paper presents the advantages of asymmetric optic concentration and illustrates the value of this design within specific PV applications.

  14. A Novel Technique for Assessing Antioxidant Concentration in Retrieved UHMWPE.

    Science.gov (United States)

    Currier, Barbara H; Van Citters, Douglas W

    2017-05-01

    identification of antioxidant content. Paired Student's t-tests were used to compare as-retrieved articular antioxidant index with expected antioxidant index (the bulk value for blended antioxidants where constant antioxidant content is expected throughout and the extrapolated original vitamin E concentration at the articular surface based on the as-manufactured vitamin E concentration gradient). Linear regression was used for each of the retrievals to evaluate the correlation of antioxidant index to ester content with the goal of extrapolation to the antioxidant index at zero ester content. On average, vitamin E index at the articular surface (0.04 ± 0.03) was reduced compared with expected vitamin E index (0.09 ± 0.04; 95% confidence interval [CI] of the difference, 0.04-0.07; p antioxidant indices at zero absorbed ester index. Absorbed esters from time in vivo caused erroneous values of antioxidant index to be calculated. However, hexane extraction to remove absorbed species also removed diffused vitamin E. Correlating antioxidant indices with ester content, measured by FTIR in unextracted antioxidant retrievals, provides a nonaltered method for estimating actual articular surface vitamin E index and demonstrates that there was no measurable elution in these short-term retrievals. Assessing antioxidant content in retrieved polyethylene inserts is important to determine how much of the antioxidant remains in place to prevent oxidation of the polyethylene over time in vivo. Retrieval analyses reporting antioxidant content must account for absorbed species to be valid. Because standard hexane extraction removes both absorbed species and vitamin E from diffused vitamin E retrievals, the correlation method presented in this study is the recommended analysis alternative.

  15. Microstructural imaging of human neocortex in vivo.

    Science.gov (United States)

    Edwards, Luke J; Kirilina, Evgeniya; Mohammadi, Siawoosh; Weiskopf, Nikolaus

    2018-03-24

    The neocortex of the human brain is the seat of higher brain function. Modern imaging techniques, chief among them magnetic resonance imaging (MRI), allow non-invasive imaging of this important structure. Knowledge of the microstructure of the neocortex has classically come from post-mortem histological studies of human tissue, and extrapolations from invasive animal studies. From these studies, we know that the scale of important neocortical structure spans six orders of magnitude, ranging from the size of axonal diameters (microns), to the size of cortical areas responsible for integrating sensory information (centimetres). MRI presents an opportunity to move beyond classical methods, because MRI is non-invasive and MRI contrast is sensitive to neocortical microstructure over all these length scales. MRI thus allows inferences to be made about neocortical microstructure in vivo, i.e. MRI-based in vivo histology. We review recent literature that has applied and developed MRI-based in vivo histology to probe the microstructure of the human neocortex, focusing specifically on myelin, iron, and neuronal fibre mapping. We find that applications such as cortical parcellation (using R 1 maps as proxies for myelin content) and investigation of cortical iron deposition with age (using R 2 * maps) are already contributing to the frontiers of knowledge in neuroscience. Neuronal fibre mapping in the cortex remains challenging in vivo, but recent improvements in diffusion MRI hold promise for exciting applications in the near future. The literature also suggests that utilising multiple complementary quantitative MRI maps could increase the specificity of inferences about neocortical microstructure relative to contemporary techniques, but that further investment in modelling is required to appropriately combine the maps. In vivo histology of human neocortical microstructure is undergoing rapid development. Future developments will improve its specificity, sensitivity, and

  16. Improving in vitro to in vivo extrapolation by incorporating toxicokinetic measurements: A case study of lindane-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Croom, Edward L.; Shafer, Timothy J.; Evans, Marina V.; Mundy, William R.; Eklund, Chris R.; Johnstone, Andrew F.M.; Mack, Cina M.; Pegram, Rex A., E-mail: pegram.rex@epa.gov

    2015-02-15

    Approaches for extrapolating in vitro toxicity testing results for prediction of human in vivo outcomes are needed. The purpose of this case study was to employ in vitro toxicokinetics and PBPK modeling to perform in vitro to in vivo extrapolation (IVIVE) of lindane neurotoxicity. Lindane cell and media concentrations in vitro, together with in vitro concentration-response data for lindane effects on neuronal network firing rates, were compared to in vivo data and model simulations as an exercise in extrapolation for chemical-induced neurotoxicity in rodents and humans. Time- and concentration-dependent lindane dosimetry was determined in primary cultures of rat cortical neurons in vitro using “faux” (without electrodes) microelectrode arrays (MEAs). In vivo data were derived from literature values, and physiologically based pharmacokinetic (PBPK) modeling was used to extrapolate from rat to human. The previously determined EC{sub 50} for increased firing rates in primary cultures of cortical neurons was 0.6 μg/ml. Media and cell lindane concentrations at the EC{sub 50} were 0.4 μg/ml and 7.1 μg/ml, respectively, and cellular lindane accumulation was time- and concentration-dependent. Rat blood and brain lindane levels during seizures were 1.7–1.9 μg/ml and 5–11 μg/ml, respectively. Brain lindane levels associated with seizures in rats and those predicted for humans (average = 7 μg/ml) by PBPK modeling were very similar to in vitro concentrations detected in cortical cells at the EC{sub 50} dose. PBPK model predictions matched literature data and timing. These findings indicate that in vitro MEA results are predictive of in vivo responses to lindane and demonstrate a successful modeling approach for IVIVE of rat and human neurotoxicity. - Highlights: • In vitro to in vivo extrapolation for lindane neurotoxicity was performed. • Dosimetry of lindane in a micro-electrode array (MEA) test system was assessed. • Cell concentrations at the MEA EC

  17. Considerations of the potential for observation of tissue function using in-vivo magnetic resonance

    International Nuclear Information System (INIS)

    Young, I.R.

    1989-01-01

    This paper concentrates on three topics - the observation of perfused flow, tissue susceptibility variations, and aspects of localized spectroscopy - to illustrate the potential offered by in vivo NMR for the study of tissue function. It concludes that while useful data can be learned now from observation of flow, the reality of the situation is that the process is going to require much more work before real biochemical observation is possible. (author)

  18. Ratiometric reactive oxygen species nanoprobe for noninvasive in vivo imaging of subcutaneous inflammation/infection

    OpenAIRE

    Zhou, Jun; Weng, Hong; Huang, Yihui; Gu, Yueqing; Tang, Liping; Hu, Wenjing

    2016-01-01

    Release of reactive oxygen species (ROS) accompanied with acute inflammation and infection often results in cell death and tissue injury. Several ROS-reactive bioluminescent probes have been investigated in recent years to detect ROS activity in vivo. Unfortunately, these probes cannot be used to quantify the degree of ROS activity and inflammatory responses due to the fact that the extent of the bioluminescent signals is also probe-concentration dependent. To address this challenge, we fabri...

  19. The in vivo estrogenic and in vitro anti-estrogenic activity of permethrin and bifenthrin.

    Science.gov (United States)

    Brander, Susanne M; He, Guochun; Smalling, Kelly L; Denison, Michael S; Cherr, Gary N

    2012-12-01

    Pyrethroids are highly toxic to fish at parts per billion or parts per trillion concentrations. Their intended mechanism is prolonged sodium channel opening, but recent studies reveal that pyrethroids such as permethrin and bifenthrin also have endocrine activity. Additionally, metabolites may have greater endocrine activity than parent compounds. The authors evaluated the in vivo concentration-dependent ability of bifenthrin and permethrin to induce choriogenin (an estrogen-responsive protein) in Menidia beryllina, a fish species known to reside in pyrethroid-contaminated aquatic habitats. The authors then compared the in vivo response with an in vitro assay--chemical activated luciferase gene expression (CALUX). Juvenile M. beryllina exposed to bifenthrin (1, 10, 100 ng/L), permethrin (0.1, 1, 10 µg/L), and ethinylestradiol (1, 10, 50 ng/L) had significantly higher ng/mL choriogenin (Chg) measured in whole body homogenate than controls. Though Chg expression in fish exposed to ethinylestradiol (EE2) exhibited a traditional sigmoidal concentration response, curves fit to Chg expressed in fish exposed to pyrethroids suggest a unimodal response, decreasing slightly as concentration increases. Whereas the in vivo response indicated that bifenthrin and permethrin or their metabolites act as estrogen agonists, the CALUX assay demonstrated estrogen antagonism by the pyrethroids. The results, supported by evidence from previous studies, suggest that bifenthrin and permethrin, or their metabolites, appear to act as estrogen receptor (ER) agonists in vivo, and that the unmetabolized pyrethroids, particularly bifenthrin, act as an ER antagonists in cultured mammalian cells. Copyright © 2012 SETAC.

  20. 2D NMR studies on muscle and cerebral metabolism in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Gillet, B.; Doan, B.T.; Verre-Sebrie, C.; Fedeli, O.; Beloeil, J.C. (Centre National de la Recherche Scientifique (CNRS), 91 - Gif-sur-Yvette (France). Inst. de Chimie des Substances Naturelles); Peres, M. (CERMA-CEV, 91 - Bretigny-sur-Orge (France)); Barrere, B.; Seylaz, J. (Paris-7 Univ., 75 (France)); Morin, S.; Koenig, J. (Bordeaux-1 Univ., 33 - Talence (France)); Sebille, A. (Faculte de Medecine Saint-Antoine, 75 - Paris (France))

    1994-06-01

    New developments in in vivo 2D[sup 1]H NMR spectroscopy now allow several metabolites, which are not resolved by 1D NMR to be assigned. This report describes the use of this technique to follow the time courses of changes in the concentration of metabolites in the rat brain during physiological and pathophysiological processes (hyperglycemia and hypoxia) and to compare the fatty acid components of normal and dystrophic mouse gastrocnemius muscle. (authors). 15 refs., 5 figs.

  1. In vitro and in vivo investigations of targeted chemotherapy with magnetic nanoparticles

    International Nuclear Information System (INIS)

    Alexiou, Christoph; Jurgons, Roland; Schmid, Roswitha; Hilpert, Andrea; Bergemann, Christian; Parak, Fritz; Iro, Heinrich

    2005-01-01

    Magnetic drug targeting is a local drug delivery system. Electromicroscopic pictures document the ferrofluid enrichment in the intracellular space in vitro. In vivo experiments were performed in VX2 tumor-bearing rabbits using magnetic nanoparticles bound to mitoxantrone. High-pressure liquid chromatography (HPLC) analyses after magnetic drug targeting showed an increasing concentration of the chemotherapeutic agent in the tumor region compared to regular systemic chemotherapy

  2. Optical assessment of nonimaging concentrators.

    Science.gov (United States)

    Timinger, A; Kribus, A; Ries, H; Smith, T; Walther, M

    2000-11-01

    An optical measurement method for nonimaging radiation concentrators is proposed. A Lambertian light source is placed in the exit aperture of the concentrator. Looking into the concentrator's entrance aperture from a remote position, one can photograph the transmission patterns. The patterns show the transmission of radiation through the concentrator with the full resolution of the four-dimensional phase space of geometric optics. By matching ray-tracing simulations to the measurement, one can achieve detailed and accurate information about the geometry of the concentrator. This is a remote, noncontact measurement and can be performed in situ for installed concentrators. Additional information regarding small-scale reflector waviness and surface reflectivity can also be obtained from the same measurement with additional analysis.

  3. Maximum Permissible Concentrations and Negligible Concentrations for pesticides

    NARCIS (Netherlands)

    Crommentuijn T; Kalf DF; Polder MD; Posthumus R; Plassche EJ van de; CSR

    1997-01-01

    Maximum Permissible Concentrations (MPCs) and Negligible Concentrations (NCs) derived for a series of pesticides are presented in this report. These MPCs and NCs are used by the Ministry of Housing, Spatial Planning and the Environment (VROM) to set Environmental Quality Objectives. For some of the

  4. Novel Electrosorption-Enhanced Solid-Phase Microextraction Device for Ultrafast In Vivo Sampling of Ionized Pharmaceuticals in Fish.

    Science.gov (United States)

    Qiu, Junlang; Wang, Fuxin; Zhang, Tianlang; Chen, Le; Liu, Yuan; Zhu, Fang; Ouyang, Gangfeng

    2018-01-02

    Decreasing the tedious sample preparation duration is one of the most important concerns for the environmental analytical chemistry especially for in vivo experiments. However, due to the slow mass diffusion paths for most of the conventional methods, ultrafast in vivo sampling remains challenging. Herein, for the first time, we report an ultrafast in vivo solid-phase microextraction (SPME) device based on electrosorption enhancement and a novel custom-made CNT@PPY@pNE fiber for in vivo