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Investigação do efeito ansíolitico-símile e antidepressivo-sí-mile do monoterpeno tetrahidrolinalol por meio de abordagens in silico e in vivo
Get PDFPharmacological therapeutic approaches to treat anxiety and depression focus on the modula-tion of neurotransmission systems involved in their neurobiology – catecholaminergic, glu-tamatergic, and oxidonitrergic pathways stand out. Among the available treatments, aromatic plants stand out as an important therapeutic resource, and their chemical constituents (e.g., monoterpenes) are being studied in the search for new treatments for anxiety and depression. Therefore, the aim of this study was to evaluate the acute toxicity as well as the anxiolytic-like and antidepressant-like potential of the monoterpene tetrahydrolinalool (THL) through in silico and in vivo models. Initially, oral treatment with THL at doses of 300 and 2000 mg/kg-1 showed low toxicity with an estimated LD50 ranging from 2000 to 5000 mg/kg-1. In addition, behavioral tests were performed in mice treated with THL (37.5-600 mg/kg-1, p.o.) using the elevated plus maze (EPM), open field (OF), rotarod (RR), and forced swim (FS) tests. Consequently, THL at doses of 37.5 and 75 mg/kg-1 induced a significant increase in the number of entries (72.7% and 64.3%, respectively) and time spent (80.3% and 76.8%, respectively) by the animals in the open arms of the elevated plus maze. However, higher doses of the compound 300 and 600 mg/kg-1) reduced the number of crossings made by the animals in the OF 30.6 % and 31.6% %, respec-tively) but did not alter their motor coordination in the RR. In the FS test, treatment with the monoterpene significantly reduced the immobility time of mice at doses of 150, 300, and 600 mg/kg-1 by 69.3%, 60.9%, and 68.7%, respectively. In molecular docking assays, THL showed satisfactory energy values compared to co-crystallized ligands for the following targets: nNOS, GCs, IL-6, 5-HT1A, NMDAr, and D1. These results were confirmed using in vivo tests, which demonstrated antagonism of the antidepressant-like effect of the monoterpene by SCH, an en-antioselective D1 antagonist. In addition, the antidepressant-like effect of THL was potentiated by ketamine, an NMDA receptor antagonist, and by methylene blue, a GCs/NO inhibitor. The latter effect was accompanied by a reduction in nitrite levels in the cortex and hippocampal structures of treated mice. Finally, the compound showed good absorption and high bioavaila-bility in silico. Taken together, the results indicate that THL is a nontoxic monoterpene, accord-ing to the protocols used. It shows good oral bioavailability and possesses a sedative effect at high doses, as well as anxiolytic- and antidepressant-like effects that appear to depend, at least in part, on dopaminergic, glutamatergic, and oxidonitrergic neurotransmission systems.Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqCoordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESAs abordagens terapêuticas farmacológicas para o tratamento da ansiedade e depressão são fo-cadas na modulação de sistemas de neurotransmissão envolvidos em sua neurobiologia – po-dendo-se destacar as vias catecolaminérgica, glutamatérgica e oxidonitrérgica. Dentre os pos-síveis tratamentos disponíveis, as plantas aromáticas são importantes arsenais terapêuticos, cu-jos constituintes químicos, a exemplo dos monoterpenos, são agentes de estudo na busca de novos tratamentos para as desordens citadas. Sendo assim, o presente estudo buscou avaliar a toxicidade aguda, o potencial ansiolítico- e antidepressivo-símile do monoterpeno tetrahidroli-nalol em modelos in sílico e in vivo. Inicialmente, o tratamento oral com THL, nas doses de 300 e 2000 mg kg-1 apresentou baixa toxicidade, e sua DL50 estimada encontra-se em valores compreendidos entre 2000 e 5000 mg kg-1. Em adição, foram realizados testes comportamentais em camundongos tratados com THL (37,5-600 mg kg-1, v.o.) e submetidos aos testes de labi-rinto em cruz elevado (LCE), campo aberto (CA), rota rod (RR) e nado forçado. (NF) Como resultado, o THL nas doses de 37,5 e 75 mg kg-1 induziu um aumento significativo no número de entradas (respectivamente em 72,7 e 64,3%) e no tempo de permanência (respectivamente 80,3 e 76,8%) dos animais nos braços abertos do LCE. Doses maiores do composto (300 e 600 mg.kg-1), no entanto, causaram uma redução do número de cruzamentos (respectivamente em 30,6 e 31,6%) dos animais no CA, mas não alteraram a coordenação motora dos mesmos no RR. No NF, o tratamento com o monoterpeno reduziu significativamente o tempo de imobili-dade dos camundongos nas doses de 150, 300 e 600 mg.kg-1, em 69,3, 60,9 e 68,7%, respecti-vamente. No tocante aos testes de ancoragem molecular, o THL apresentou valores de energia satisfatórios, quando comparados aos ligantes co-cristalizados, para os seguintes alvos: nNOs, GCs, IL-6, 5-HT1A, NMDAr e D1. Esses resultados foram corroborados nos testes in vivo, onde foi possível evidenciar o antagonismo do efeito antidepressivo símile do monoterpeno pelo SCH, um antagonista D1 enantioseletivo; além disso, o efeito antidepressivo-símile do THL foi potencializado pela cetamina, um antagonista do receptor NMDA e pelo azul de metileno, um inibidor da GCs/NOs. Esse último efeito foi acompanhado da redução dos níveis de nitrito em estrutura de córtex e hipocampo dos camundongos tratados. Por fim, a substância em questão apresentou boa absorção e alta biodisponibilidade in silico. Tomados em conjunto, os resultados indicam que o THL é um monoterpeno destituído de toxicidade, segundo os protocolos utiliza-dos, apresenta boa biodisponibilidade oral e é dotado de efeito ansiolítico-símile em doses bai-xas e sedativo e antidepressivo-símile em doses altas, sendo esse último efeito dependente, pelo menos em parte, dos sistemas de neurotransmissão dopaminérgico, glutamatérgico e oxidoni-trérgico
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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