1,721,003 research outputs found
PRUDENT USE OF FLUOROQUINOLONES IN AVIAN SPECIES: PHARMACOKINETICS OF FLUMEQUINE AND ENROFLOXACIN FOR PK/PD MODELLING IN TURKEY.
Full text linkThe importance of prudent and rational use of antimicrobial is important, not only to safeguard the efficacy of these drugs in humans and veterinary medicine but, even more so, to prevent the emergence and spread of undesirable resistance phenotypes in zoonotic pathogens as well as in commensal bacteria that can be transmitted between animals and humans.
Even more importance and attention is now given to the prudent use of medically important antimicrobial drugs, referring to those drugs for human therapeutic use.
The fluoroquinolones belong to this category. These are very potent antimicrobials and active against a wide range of pathogenic organisms and are well distributed in the body after administration. This class of antimicrobials has a therapeutic effect on most infections in different organs or tissues. Although it is rare that fluoroquinolones are the only available agent for treatment of a specific infectious disease, fluoroquinolones are important alternative medicinal products for a veterinarian to have as option for treatment. Fluoroquinolones have a unique mechanism of action not related to conventional antimicrobials, and therefore their efficacy should be retained as long as possible.
The avian production increased enormously in the last 50 years and the European Union (EU) is one of the world's top producers in poultry meat and a net exporter of poultry products. In this production, turkeys that is considered a “minor species”, but it is important in the livestock production of Italy. Scarce data exist about the usage of antimicrobial drugs in turkey and even less is known about their efficacy. As the limited number of medicinal products authorized in this species, antimicrobial therapy is frequently carried out with the few products authorized or with drugs “extra-label” used with the consequence of increases of selective pressure and also with the possibility of cross-resistance within the same pharmacological group of compounds.
The studies reported in this thesis aimed to revise the use of fluoroquinolones in turkey to maintain the efficacy and reduce the spread of resistance against E.Coli, the most common zoonotic avian pathogen. Pharmacokinetic(PK)/pharmacodynamics (PD) models are the best tool in order to select optimal dosage regimen. To confirm dosages used at farms and allow the integration of PK/PD data, the plasma concentrations in blood from healthy animals collected during treatment with flumequine and enrofloxacin, were determined.
The first step was to optimize and validate a fast, simple, sensitive, and specific liquid chromatography-mass spectrometry (LC-MS)/MS/MS method suitable for the detection of a wide range of concentrations of fluoroquinolones as those occurring in pharmacokinetic and residue depletion studies from several matrices. The first trial presents a sensitive and reliable confirmatory method for the extraction, identification, quantification of five fluoroquinolones . For the extraction and matrix clean-up of fluoroquinolones residues from all biological matrices, the Quick Easy Cheap Effective Rugged Safe (QuEChERS) methodology was adopted; only for plasma samples acetonitrile was used. The analyses were performed by (LC-MS. LC separation was performed on a C18 Kinetex column (100x2.1 mm, 2.6 μm, Phenomenex, CA, USA) with gradient elution using ammonium acetate solution (10 mM, pH 2.5) and methanol containing 0.1% formic acid. Mass spectrometric identification was done using an LTQ XL ion trap (Thermo Fisher Scientific, CA, USA), with a heated electrospray ionization probe, in positive ion mode. The method was validated according to the European Legislation (decision 2002/657/EC) and EMA guideline (EMA/CVMP/VICH/463202/2009); selectivity, linearity response, trueness (in terms of recovery), precision (within-day repeatability and within-laboratory reproducibility), limit of detection, limit of quantification, decision limits, detection capability, absolute recovery and robustness were evaluated using turkey blank matrices. All data were within the required limits established for confirmatory methods except for flumequine which presented a recovery value slightly higher than 110% in muscle and intestinal content. For all fluoroquinolones, all the extraction rates were greater than 70% and limits of quantification ranged from 1.2 μg/kg to 118.8 μg/kg. This method was suitable for the identification and quantification of fluoroquinolones in plasma samples of turkeys treated for the purpose of second and third trials.
In the second trial, the PK behavior of flumequine administered to 32 healthy turkeys as an oral bolus via gavage or as 5 days of 10-hours pulsed administration in drinking water were compared, using the EU authorized dose of 15 mg/kg and the double dose of 30 mg/kg. The MIC of 235 Escherichia coli field strains isolated from poultry were determined for PD to develop a PK/PD model. Blood samples were collected at established times over 24 h, and the obtained plasma was analyzed using the LC-MS/MS/MS method previously described. A monocompartmental model and a noncompartmental model were applied to the data to obtain the PK results. The maximum concentration (Cmax)/MIC50 and the plasma concentration-time curve from 0 to 24 hours (AUC0–24)/MIC50 ratios were, respectively, 0.67 ± 0.09 and 4.76 ± 0.48 and 1.18 ± 0.35 and 7.05 ± 2.40 for the 15 and 30 mg/kg bolus doses, respectively. After 10-hours pulsed administration of 15 mg/kg, values of Cmax/MIC50, 0.19 ± 0.02 on day 1 and 0.30 ± 0.08 on day 5 of therapy were obtained, the AUC/MIC50 ratios were 2.09 ± 0.29 and 3.22 ± 0.93 on d 1 and 5, respectively. Higher values were obtained with the doubled dose of 30 mg/kg: the Cmax/MIC50 ratios were 0.49 ± 0.11 on day 1 and 0.69 ± 0.18 on day 5; the AUC/MIC50 ratios were 5.15 ± 1.15 and 6.57 ± 1.92 on d 1 and 5, respectively. For both types of administration and both dosages, the Cmax/MIC50 and the AUC/MIC50 ratios achieved were significantly lower than the fluoroquinolones breakpoints usually considered for efficacy.
The last trial involving 50 healthy turkeys, was conducted to evaluate the efficacy of enrofloxacin. As in the previous study, the effectiveness of different treatment schemes against E. coli was evaluated by a PK/PD approach, correlating the PK results with the MIC determined for 235 E. coli strains.
In this study, 3 different oral treatments (a single oral gavage, 5 days of 10-hours pulsed water medication, and 5 days of 24-hours continuous water medication) and single parenteral (subcutaneous; SC) treatment using 2 different doses of enrofloxacin (i.e., the EU authorized dose, 10 mg/kg, and double the EU recommended dose, 20 mg/kg) were evaluated. Blood samples were collected at established times over 24 h. Plasma was analyzed using a LC-MS/MS/MS that was validated in house. A monocompartmental and a noncompartmental model were applied to the data to obtain the PK results. After gavage administration, the mean maximum concentration Cmax/MIC50 and area under the curve AUC0–24/MIC50 ratios were, respectively, 3.07 ± 0.62 and 7.01 ± 1.03 and 25.48± 3.04 and 57.2 ± 3.73 for the 10 and 20 mg/kg doses, respectively. After SC administration of 10 mg/kg, Cmax/MIC50 and AUC0–24/MIC50 ratios were 3.45 ± 0.75 and 33.96 ± 7.46, respectively. After the administration of 10-h pulsed or 24-h continuous medicated water at 20 mg/kg, lower values of Cmax/MIC50 (10-h pulsed: 3.45 ± 0.7; 24-h continuous: 3.05 ±0.48) and AUC0–24/MIC50 (10-h pulsed: 42.42 ± 6.17; 24-h continuous: 53.32 ± 5.55) were obtained. Based on these results, the European Union-recommended dosage of 10 mg/kg seems ineffective to achieve adequate drug plasma concentrations and even the 20 mg/kg by 10 h pulsed or continuous medicated water administration did not reach completely efficacious concentrations in plasma against colibacillosis. Although the results obtained were not completely encouraging, the medicated water should preferably be provided continuously. To conclude about the efficacy of enrofloxacin treatment against colibacillosis, target tissue concentration should be extensively considered
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Pharmacokinetics and effects of alkalization after intravenous administration of Eltenac in horses
No full textEltenac (ELT) [4-(2,6-dichlorophenyl)amino-3-thiophene] is a non-steroidal anti-inflammatory drug (NSAID) that was developed for veterinary use in horses and cattle. The pharmacokinetics of ELT was evaluated in horses at 0.5 mg/kg body weight (BW) after single IV injection after 5 days of repeated IV administration and after a single IV injection in horses previously subjected to 250 mg/kg BW of sodium bicarbonate (NaHCO3) as an alkalization treatment. The aim was to determine whether blood and subsequent urinary alkalization could modify the pharmacokinetics of ELT. Drug quantification was performed with serum and urine using high performance liquid chromatography with UV-visible detection. The results were also integrated with cyclo-oxygenase-inhibition literature data to review the dosage scheme of ELT in horses. After a single intravenous administration, ELT was characterized by rapid distribution (mean t1/2λ1 = 0.18 ± 0.07 hour) and a short elimination half-life (mean t1/2λ2 = 2.9 ± 0.68 hour). The volume of distribution was small (Vdss = 253.51 ± 47.55 mL/kg), which is likely because of the high percentage of drug protein binding (approximately 97%). The AUC0-∞ and ClB were 6.92 ± 0.84 h*μg/mL and 73.2 ± 10 mL/h/kg, respectively. Repeated administration did not cause either accumulation or modification of the pharmacokinetic profile. The invitro effective concentrations were maintained for a 6-hour period. The alkalization procedure appeared to accelerate drug elimination, as ELT was quantifiable only for 6 hours; however, the drug clearance was not significantly modified. Thus, the administration of alkaline compounds to accelerate the elimination of ELT is not completely confirmed
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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