1,720,967 research outputs found

    Use of cultured goat and cattle hepatocytes to investigate xenobiotic oxidative metabolism

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    The oxidative metabolism of aldicarb (ALD), a carbamate pesticide, and fenbendazole (FBZ), an anthelmintic, was studied using cultured hepatocytes obtained from 4 goats and a bullock and incubated with ALD (50 mumol/L) and FBZ (10 mumol/L). The parent compounds and the metabolites were measured by HPLC. Both compounds are metabolized at the sulphur atom via two sequential oxidations, first to the sulphoxide (aldicarb sulphoxide and oxfendazole, respectively) and then to the sulphone. Oxfendazole and fenbendazole sulphone from FBZ, and aldicarb sulphoxide from ALD were found in both species. Aldicarb sulphone was not produced by the hepatocyte preparations from the bullock. The good correlation obtained comparing the in vitro results of FBZ metabolism with published in vivo data obtained on FBZ kinetics in the same species confirmed the usefulness of in vitro models for predictive analysis of in vivo xenobiotic biotransformation

    PK/PD of flumequine in pigs after intravenous and intramuscular administration

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    Flumequine is a second generation antibacterial quinolone derivative, developed solely for use in animals. The drug is widely employed in food-producing species (ruminants, pigs, birds, fish) to control infections caused by a range of Gram-negative bacteria and is commonly administered at doses of 5-6 up to 15 mg.kg-1 b.w. every 12 hours. The kinetic behavior of flumequine has been studied in many animal species but not in pigs and dosing in these animals are to some extent empirical as it is based on results obtained in other animals. In this study the pharmacokinetics and intramuscular bioavailability of flumequine (15 mg.kg-1) in pigs were determined and the findings related to published minimal inhibitory concentrations (MICs) for susceptible bacteria of animal origin and to experimentally determined MICs for susceptible strains of porcine origin. We determined MICs for Escherichia coli, Salmonella spp., Pasteurella spp. and Bordetella spp isolated from infected pigs in the Forlì area of Italy; Pasteurella multocida strains were particularly sensitive (MIC90 = 0.5 μg.mL-1). After intravenous injection flumequine was slowly distributed and eliminated (t1⁄211.40±0.16 h and t1⁄226.35±1.69 h). The distribution volume at steady state (Vdss) was 752.59±84.03 mL.kg-1 and clearance (ClB) was 237.19±17.88 mL.kg-1.h-1. The bioavailability was about 85%. The PK/PD analysis allows to conclude that flumequine could be effective in controlling respiratory infections caused by Pasteurella multocida, while its effectiveness against gastrointestinal infections caused by Salmonella typhimurium and Escherichia coli may be impaired by the emergence of less sensitive or resistant strains

    Intramuscular bioavailbility of Ketoprofen lysine salt in horses

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    Lysine salts are often used in human pharmaceuticals to increase the solubility and absorption of acidic drugs when these are administered parenterally. In this study the intramuscular bioavailability of ketoprofen administered as the lysine salt was evaluated in horses (n = 5) treated intravenously and intramuscularly (2.2 mg/kg active substance) in a cross-over study. The absorption rate of ketoprofen administered as the lysine salt was rather low: the mean residence time increased from 31.7 min after IV injection to 128.9 min (after IM injection), and the bioavailability was high (mean 92.4%). The calculated steady state plasma concentrations of ketoprofen during multiple dosage were much higher after intramuscular (0.106 g/ml) than after intravenous (0.066 microgram/ml) administration. Intramuscular injections of the ketoprofen lysine salt can therefore be given to horses, which are particularly prone to develop soft tissue reactions, since use of the lysine salt markedly reduced local irritation at the injection sit

    Pharmacodynamics and pharmacokinetics of cefoperazone and cefamandole in dogs following single dose intravenous and intramuscular administration

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    The pharmacokinetics and intramuscular (i.m.) bioavailability of cefoperazone and cefamandole (20 mg/kg) were investigated in dogs and the findings related to minimal inhibitory concentrations (MICs) for 90 bacterial strains isolated clinically from dogs. The MICs of cefamandole for Staphylococcus intermedius (MIC90 0.125 mcg/mL) were lower than those of cefoperazone (MIC90 0.5 mcg/mL) although the latter was more effective against Escherichia coli strains (MIC90 2.0 mcg/mL vs. 4.0 mcg/mL). The pharmacokinetics of the drugs after intravenous administrations were similar: a rapid distribution phase was followed by a slower elimination phase (t(1/2)lambda2 84.0 ± 21.3 min for cefoperazone and 81.4 ± 9.7 min for cefamandole). The apparent volume of distribution and body clearance were 0.233 L/kg and 1.96 mL/kg/min for cefoperazone, 0.190 L/kg and 1.76 mL/kg/min for cefamandole. After i.m. administration the bioavailability and peak serum concentration of cefamandole (85.1 ± 13.5% and 35.9 ± 5.4l mcg/mL) were significantly higher than cefoperazone (41.4 ± 7.1% and 24.5 ± 3.0l mcg/mL), but not the serum half-lives (t(1/2)el 134.3 ± 12.6 min for cefoperazone and 145.4 ± 12.3 min for cefamandole). The time above MIC90 indicated that cefamandole can be administered once daily to dogs for the treatment of staphylococcal infections (T > MIC for S. intermedius 23.8 ± 0.3 and for Staphylococcus aureus 21.6 ± 0.6 h)

    Relative Bioavailability of microgranulated Sulfamethazine in veal calves

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    The kinetics of free and microgranulated sulfadimidine were compared in milk-fed calves dosed orally (180 mg/kg) in a crossover study. Microgranulation results in delayed absorption of sulfadimidine and poor bioavailability, with the area under the plasma concentration-time curve (AUC(0-infinity)) reduced from 7400 to 3781 micrograms.h/mL, and maximum plasma concentration (Cmax) reduced from 188.1 +/- 39.0 to 84.41 +/- 22.6 micrograms/mL. It is concluded that sulfadimidine microgranulated with long chain fatty acids is not suitable for use in milk-fed calves; the gastrointestinal transit time is too rapid to allow full release of the drug, markedly limiting its bioavailability. In adult animals, or in the young of other animal species in which digesta transit time is slower than in calves, the bioavailability of microgranulated sulfadimidine may be much greate

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

    Influenza della microincapsulazione con acidi grassi sui processi di assorbimento nel suino

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    I risultati fanno ritenere che la microincapsulazione con acidi grassi saturi a lunga catena possa, accanto ai vantaggi di ordine tecnologico (migliore dispersione, ridotta polverulenza e contaminazione, ecc..), non interferire negativamente sull'assorbimento e sulla disponibilità della sulfametazina, usata quale indicatore per i nutrienti

    Variations on the Author

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    “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

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We 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
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