1,721,095 research outputs found
Description of analytical approaches to compare ketamine pharmacokinetics in feline dried blood spots and plasma
No full textIntroduction: Pharmacokinetic studies are usually based on measuring the target drug in plasma or serum; however, to obtain a sufficient amount of sample to perform analytical investigations, collecting at least 1 mL of blood at each time points is often required. For this reason, mini-invasive and ethically accepted alternatives to traditional sampling techniques are encouraged, especially in studies involving small size animals. Dried blood spot (DBS), first introduced to screen for diseases in new-borns, has recently gained relevance for pharmacokinetic and toxicokinetic studies in human medicine, but it has not been similarly considered in veterinary medicine so far. In this context, it would be interesting to explore the applicability of DBS for accurate quantification of selected drugs in companion animals.
Objectives: The aim of the present work was to develop analytical methods for the correct quantification of ketamine in plasma and DBS samples collected from cats, allowing to compare its concentration/time profile in the two matrices.
Materials and Methods: Ketamine was extracted from 100 μL of plasma through protein precipitation with acetonitrile and from 20 μL DBS using a 30:70 H2O:ACN solution. Chromatographic separation was obtained with a Waters Acquity UPLC pump equipped with a BEH C18 column, pumping a mixture of 0.1% formic acid in water and acetonitrile under programmed conditions. Quantification of the analyte was performed on a Waters XEVO TQ-S Micro, operating in positive electrospray ionization and monitoring two specific transitions (238.1>124.9 and 238.1>207.0). A preliminary application of the analytical approaches was performed on samples collected (T0, T10, T15, T20, T30, T45 and T60) from two male cats receiving 10 mg/kg of ketamine and 20 mg/kg of medetomidine intramuscularly for neutering.
Results and Discussion: The proposed LC-MS/MS approach is under validation following the most recent European guidelines. In both matrices, linearity was assessed (R2>0.99) over the 250-5000 ng/mL range; accuracy and precision were calculated at four concentrations, providing values always within ±13% and below 11%, respectively. Samples analysed during the pilot study proved that the tested range was suitable for real plasma and DBS concentrations.
Conclusions: We developed two quick and simple analytical approaches for the determination of the pharmacokinetic profile of ketamine in cat plasma and DBS. Their application to a larger number of patients will allow to calculate the main PK parameters in the two types of samples, and to confirm if DBS can represent a mini-invasive alternative to plasma during multiple time-point experiments
Melatonin and Related Compounds as Antioxidants
Full text linkOxidative stress has been reported to be involved in the onset and development of several diseases, including neurodegenerative and cardiovascular disorders, some types of cancer, and diabetes. Therefore, finding strategies to detoxify free radicals is an active area of research. One of these strategies is the use of natural or synthetic antioxidants. In this context, melatonin (MLT) has been proven to possess most of the required characteristics of an efficient antioxidant. In addition, its protection against oxidative stress continues after being metabolized, since its metabolites also exhibit antioxidant capacity. Based on the appealing properties of MLT and its metabolites, various synthetic analogues have been developed to obtain compounds with higher activity and lower side effects. This review addresses recent studies with MLT and related compounds as potential antioxidants
Peter Munz. — Frederik Barbarossa. A Study in Medieval Politics
No full textLabande Edmond René, Labande-Mailfert Yvonne, Brezzi Paolo. Peter Munz. — Frederik Barbarossa. A Study in Medieval Politics. In: Cahiers de civilisation médiévale, 13e année (n°52), Octobre-décembre 1970. pp. 386-387
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
Physiological role of nitric oxide and its contribution to vascular regulation during exercise
No full textA quick approach for medetomidine enantiomer determination in dog plasma by chiral liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study
Full text linkIn the present study, a rapid, sensitive and high-throughput liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of medetomidine enantiomers in dog plasma was developed and validated. The separation and individual quantification of chiral compounds can be a tricky task in LC. This is particularly true when target analytes have a relatively small mass, as is the case with medetomidine, a potent and highly specific α2-adrenoceptor agonist widely used in both human and veterinary medicine. The proposed approach is based on a quick liquid–liquid extraction with ethyl acetate and filtration prior to injection. The optimized mobile phase composition allowed to perfectly separate the two enantiomers of medetomidine in a short chromatographic run time, using a cellulose tris(4-methylbenzoate)-based chiral column. A lower limit of quantification of 0.1 ng/mL was reached for both analytes thanks to the high sensitivity and selectivity of MS/MS and the use of racemic medetomidine-d3 as internal standard prevented potential matrix effect. Linearity was satisfying (R2 > 0.99) over the range 0.1–25 ng/mL, as well as within- and between-session accuracy and precision, both always <15%. This method was also applied with success to a series of samples from a pharmacokinetic (PK) study aimed at comparing dex- and levomedetomidine behaviour after administration of the racemic mixture in dogs. The simple extraction procedure, which allows reduced solvent and time consumption without compromising analytical performances, makes this technique a useful tool for this kind of applications even when small animals are involved, due to the small amount of sample required
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
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
- …
