1,720,983 research outputs found
Saccharolactone: the history, the myth, and the practice
No full textOver the past two decades, saccharolactone has been routinely used in in vitro microsomal incubations, and sometimes in incubations with recombinant Uridine diphosphoglucuronosyl transferases (UGT) while investigating glucuronidation reactions. The addition of saccharolactone is aimed at completely inhibiting β-glucuronidases that may be present in the microsomes, in the anticipation of accurate identification and quantification of the formed glucuronide metabolites. Recent research has demonstrated that saccharolatone may not serve the intended objective, and may even lead to inhibition of certain UGTs. This report investigates the historic evidence in the practice of saccharolactone addition in relation to β-glucuronidases and UGTs. The chemical nature and inhibition potency of saccharolactone are explored in an attempt to unravel the myth in its application. Finally, the collective evidence is discussed in an effort to provide guidance to drug metabolism scientists on the utilization of saccharolactone
Unusual Glucuronides
No full textGlucuronidation reaction is catalyzed by Uridine diphosphoglucuronosyl transferases (UGTs), enzymes present in mammalian species, by utilizing uridine diphosphoglucuronic acid (UDPGA) as a co-substrate. Conjugation of glucuronic acid to nucleophilic functional groups in chemical entities results in the formation of glucuronides. This metabolic process involves a nucleophilic attack by a given functional group of the substrate on C-O bond of UDPGA, ultimately resulting in cleavage of that bond along with the formation of a glucuronide and uridine diphosphate as a by-product. As anticipated, a number of nucleophilic functional groups such as hydroxyl, phenolic, acyl, primary secondary and tertiary amino, in a diverse set of chemical compounds are known to form the corresponding glucuronides. Glucuronides are believed to be the end products of metabolism. The objective of this review however, is to highlight unusual glucuronide conjugates. Furthermore, due to the mechanistic and chemical differences observed for two different types of diglucuronides reported so far, a classification is proposed. Overall, this commentary centers on uncommon glucuronides and also draws attention to glucuronides undergoing ensuing oxidative or conjugative metabolic transformations
An experimental approach to enhance parent ion fragmentation for metabolite identification studies: Application of dual collision cells in an orbital trap
No full textRecent mass spectrometry advancements including data-dependent scanning and high resolution mass spectrometry have aided metabolite profiling for non-radiolabeled xenobiotics. However, narrowing down a site of metabolism is often limited by the quality of collision induced dissociation (CID) based parent ion fragmentation. An alternative dissociation technique, higher energy collisional dissociation (HCD), enriches compound fragmentation and yields “triple quadrupole like fragmentation”. Applying HCD along with CID and data dependent scanning could enhance structural elucidation for small molecules. LC-MSn experiments with CID and HCD fragmentation were run for commercially available compounds on orbital trap, a hybrid linear ion trap-orbitrap mass spectrometer equipped with accurate mass measurement capability. The developed method included stepped normalized collision energy (SNCE) parameters to enhance MS fragmentation without tuning of compounds. All evaluated compounds demonstrated improved fragmentation under HCD as compared to CID. Results suggest that an LC-MSn method that incorporated both SNCE HCD and CID enabled parent ion fragmentations, afforded comprehensive structural information for the compounds under investigation. Such a method was remarkably better than one with only CID MSn in an ion trap. It is evident that such an acquisition method can augment identification of unknown metabolites in drug discovery by improving fragmentation efficiency of both the parent compound and putative metabolite(s)
Mesentery: An ADME perspective on a 'new' organ
No full textWith the inclusion of mesentery, the total number of human organs has recently increased by one. Mesentery was formerly construed to be a complex, discontinuous anatomical structure simply serving as a support for organs in abdominal cavity. However, the recent research has established mesentery to be a far more simple and unfragmented organ. The newly emerged information on mesentery has challenged the older pathophysiological concepts. This review briefly discusses the anatomy of the mesentery, historical perspective on mesentery, embryology, drug metabolizing enzymes and transporters of the mesentery, and mesentery’s role in diseases. The possible impact of mesentery on absorption, distribution, metabolism and excretion (ADME) is also discussed
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
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