1,720,958 research outputs found
Influence of morphine on cytokine production on horses stimulated with LPS in in vitro and in vivo
No full textA síndrome da resposta inflamatória sistêmica (SIRS) é uma condição inflamatória exacerbada, desencadeada, dentre outras causas, pela liberação de endotoxinas na circulação e está relacionada à falência de órgãos e morte. As causas de endotoxemia que culminam na SIRS em equinos incluem pleuropneumonia, abdome agudo, endometrite e sepse neonatal. Para evitar o desfecho da afecção, além do tratamento do fator causal, o controle na produção de citocinas e mediadores inflamatórios é almejado. Devido às propriedades imunomoduladoras constatadas em humanos, camundongos e em sinoviócitos de equinos, a morfina é um fármaco com potencial terapêutico para a SIRS em equinos em quadros endotoxêmicos. Com o estudo objetivou-se verificar a influência da morfina na produção das citocinas pró-inflamatórias IL1-β, TNF-α e IL-6 por células imunológicas de equinos in vitro e após a indução experimental de endotoxemia com lipopolissacarídeo (LPS) in vivo. Para isso, o estudo foi conduzido em duas fases. A primeira realizada in vitro, em dois ensaios, com a seleção de nove animais, com idade entre 1 e 2 anos, hígidos e sem histórico de doenças causadas por bactérias gram-negativas. Desses animais, foram coletados 20 mL de sangue, por meio de punção da veia jugular. No primeiro ensaio, 5 x 105 células foram submetidas a um dos tratamentos: LPS (controle positivo), meio diluente (controle negativo), meio com 300 µM/mL de morfina (controle negativo + morfina) e 30, 100 e 300 µM/mL de morfina com LPS. No segundo ensaio, células foram cultivadas com LPS, meio, meio com 300 µM/mL de morfina, 300 µM/mL de morfina com LPS ou 300 µM/mL de morfina + 30 µM/mL de naloxona + LPS. Após 24 horas, o sobrenadante foi coletado para análise de TNF-α, IL-1β e IL-6, por ELISA. A segunda etapa consistiu na fase in vivo em que foram selecionados 12 equinos hígidos e sem histórico de doenças causadas por bactérias gram-negativas, que receberam 100 ng/kg de LPS diluído em 250 mL de solução NaCl 0,9%, infundidos pela via intravenosa (IV) em 15 minutos. Após a indução da endotoxemia com LPS, os animais foram distribuídos aleatoriamente em dois grupos (n = 6): Morfina, os quais receberam 0,1 mg/kg de morfina IV imediatamente após a infusão de LPS; e Salina que receberam volume proporcional de NaCl 0,9%, no mesmo momento. Para análise de hemograma, fibrinogênio e mensuração de citocinas pelo método de ELISA, foram coletadas amostras antes dos tratamentos T0 (basal) e após a injeção de LPS, nos tempos 15 e 30 minutos, 1, 2, 3, 4, 5 e 6 horas. O nível de significância adotado foi de 5% (p < 0,05). Para realizar comparações estatísticas, os valores foram transformados em logaritmo. No primeiro ensaio verificou-se que a dose de 300 µM/mL de morfina reduziu a produção de IL-1β e IL-6. No segundo ensaio observou-se que a dose 300 µM/mL de morfina reduziu a produção de IL-1β e a naloxona foi capaz de antagonizar esse efeito. In vivo a morfina atenuou os sinais relacionados a dor e apatia e reduziu a produção de TNF-α e de IL-1β. Dessa maneira, verificou-se que a morfina in vitro reduziu a produção de citocinas pró-inflamatórias por células imunológicas de equinos, sendo seus efeitos parcialmente revertidos pela naloxona. Verificou-se ainda que o fármaco possui potencial imunomodulador quando administrada de forma sistêmica em equinos e não suprimiu totalmente a função imunológica.The systemic inflammatory response syndrome (SIRS) is defined as an exaggerated inflammatory condition triggered, among multiple factors, by the release of endotoxins in the blood stream, and is associated with multiple organ failure and, ultimately, death. In horses, the causes of endotoxemia that could result in SIRS include pleuropneumonia, acute abdomen, endometritis and neonatal sepsis. Avoiding such life-threatening outcome encompass the treatment of the given source of inflammation and the control of cytokine and inflammatory mediators production. Because of the immune modulator properties of morphine documented in humans, mice and equine synoviocytes, this opioid represents a potential therapeutic drug for SIRS in horses experiencing endotoxemia. The aim of the current study was to assess the in vitro influence of morphine on pro-inflammatory cytokine production, including IL1-β, TNF-α and IL-6, as generated by equine immune cells, and to investigate their in vivo production following experimentally-induced endotoxemia with lipopolysaccharide (LPS). To do so, this study was designed in a two-phase fashion. For the first phase, two in vitro trials were performed, which used healthy, 2- to 4-year old horses (n = 6) with no history of previous disorders caused by gram-negative bacteria. Blood (20 mL) was collected from these horse by jugular venipuncture. First, 5 x 105 cells were submitted to one of the four treatments: LPS (positive control), diluent solution (negative control), diluent solution enriched with 300 µM/mL morphine (negative control + morphine) and 30, 100 and 300 µM/mL morphine added to LPS. Afterwards, cell culture was carried out with LPS alone, diluent solution alone, diluent solution with 300 µM/mL morphine, 300 µM/mL morphine with LPS or 300 µM/mL morphine + 30 µM/mL naloxone + LPS. After 24 hours, the supernatant was separated cleanly for measuring TNF-α, IL-1β e IL-6 by ELISA. The second phase involved an in vivo approach, where 12 healthy horses with no background of systemic diseases caused by gram-negative bacteria received LPS at 100 ng/kg diluted with 250 mL of saline (0.9% NaCl), as administered intravenously (IV) over 15 minutes. Once LPS-induced endotoxemia took place, animals were randomly assigned to two groups: morphine, in that 0.1 mg/kg morphine was administered IV immediately past LPS infusion, and saline, which received an equal volume of 0.9% NaCl at the same time point. For blood count and fibrinogen evaluation, as well as cytokine quantification by ELISA, blood samples were obtained before (T0; baseline) and after treatment at specific time points, namely 15 minutes, 1, 2, 3, 4, 5 and 6 hours. Significance level was set at 5% (p < 0.05). For statistical comparisons, the values were converted into logarithms. In the first trial the highest concentration of morphine reduced the production of IL-1β and IL-6. Second trial studies revealed it was observed that the 300 µM/mL dose of morphine reduced the production of IL-1β and naloxone was able to antagonize this effect. As far as its in vivo effects, morphine mitigated the clinical signs of endotoxemia significantly decreased TNF-α and IL-1β synthesis. Therefore, it was found that morphine in vitro reduced the production of pro-inflammatory cytokines by equine immune cells, and their effects were partially reversed by naloxone. Furthermore, this opioid holds potential immune modulator effects when given systemically to horses while not fully suprassing immunological function
Effects of morphine and methadone on the behavior and tumor growth of mice with Ehrlich tumor
No full textA morfina e a metadona, embora sejam fármacos recomendados para promover analgesia, parecem promover alterações comportamentais e influenciar no crescimento tumoral em modelos experimentais. Diante disso, o objetivo do estudo consistiu em avaliar os efeitos da morfina e metadona sobre o comportamento, antinocicepção e crescimento tumoral em camundongos. O estudo foi dividido em duas partes. No primeiro experimento foram utilizados 53 camundongos, fêmeas, com 60 ± 10 dias de idade que foram inoculados com tumor ascítico de Ehrlich (TAE) por via intraperitoneal. Após sete dias da inoculação, os animais foram distribuídos aleatoriamente em 7 grupos, morfina 5 mg/kg (Morf5), morfina 7,5 mg/kg (Morf7,5), morfina 10 mg/kg (Morf10), metadona 2,85 mg/kg (Met2,85), metadona 4,3 mg/kg (Met4,3), metadona 5,7 mg/kg (Met5,7) e solução salina NaCl 0,9% (Salina). Os tratamentos foram administrados por via subcutânea, a cada seis horas, durante três dias. Os animais foram avaliados quanto a atividade geral em campo aberto e nocicepção, por meio do teste de pinçamento de cauda, os quais foram realizados antes da inoculação tumoral (dia 0), aos 40, 90, 150, 240 e 360 minutos após o início dos tratamentos (dia 7) e 40, 150 e 360 minutos após os dias 8 e 9 pós-inoculação. Todas as doses promoveram aumento significativo da distância percorrida e velocidade média de maneira dose-dependente, sendo que os efeitos foram mais pronunciados nos dias 8 e 9. As frequências de levantar e de autolimpeza reduziram de maneira significativa após a administração de morfina e metadona em todas as doses até os 90 minutos. O segundo experimento consistiu em avaliar os efeitos sobre o crescimento tumoral das mesmas doses da morfina e metadona administradas por via subcutânea, a cada 6 horas, durante 8 dias, iniciados 24 horas após a inoculação tumoral. Os animais foram avaliados diariamente quanto ao peso e circunferência abdominal e nove dias após a inoculação tumoral, foram submetidos à eutanásia. O líquido ascítico foi colhido para aferição do volume, verificação da característica do líquido, contagem de células tumorais e análise do ciclo celular. Todos os animais apresentaram aumento de peso e de circunferência abdominal ao longo dos dias. O volume do líquido ascítico peritoneal foi menor nos tratamentos Morf5, Morf10 e em todas as doses testadas de metadona em comparação ao grupo Salina. A viabilidade e o número de células totais não diferiram entre os tratamentos. Os tratamentos Morf10 e Met5,7 interferiram no ciclo celular das células tumorais com maior porcentagem de células na fase G1 do ciclo, em comparação ao grupo Salina. Observou-se, a partir do primeiro experimento que todas as doses testadas promovem aumento da locomoção e redução de comportamentos exploratórios que foram mais evidentes ao longo dos dias de tratamento. A antinocicepção é observada por até 40 minutos em dose única e prolonga-se por até 150 minutos após administrações seriadas nas doses intermediárias e maiores. Os tratamentos Morf10 e Met5,7 promovem estase do ciclo celular, mas não interferem de maneira significativa no crescimento do tumor ascítico de Ehrlich.The objective of this research is to evaluate the effects of morphine and methadone on behavior, antinociception and tumor growth in mice. The study was dived into two parts. In the first experiment, Fifty-three female mice, 60 ± 10 days old, were inoculated with Ehrlich\'s ascitic tumor (EAT) intraperitoneally. Seven days after intraperitoneal tumour inoculation (2 × 106 cells), the animals were randomised into seven groups: morphine 5 mg/kg (MO5), morphine 7.5 mg/kg (MO7.5), morphine 10 mg/kg (MO10), methadone 2.85 mg/kg (ME2.85), methadone 4.3 mg/kg (ME4.3), methadone 5.7 mg/kg (ME5.7), and 0.9% NaCl (Sal). Treatments were administered subcutaneously, every 6 h, for 3 days. The animals were evaluated for general activity and nociception using the open field and tail clip tests, respectively. These tests were performed before tumour inoculation (day 0); at 40, 90, 150, 240, and 360 min following treatment initiation (day 7); and at 40, 150, and 360 min after days 8 and 9 post-inoculation. All evaluated doses promoted a significant dose-dependent increase in the total distance travelled and the average speed, markedly pronounced on days 8 and 9 than on day 7. The frequencies of rearing and self-grooming decreased significantly after morphine or methadone administration. The second experiment consisted of evaluating the effects on tumor growth of the same doses of morphine and methadone administered subcutaneously, every 6 hours, for 8 days, starting 24 hours after tumor inoculation. The animals were evaluated daily for weight and abdominal circumference and they were euthanized nine days after the tumor inoculation. The ascitic fluid was collected to measure the volume, check the characteristic of the liquid, count the tumor cells and analyze the cell cycle. All animals had increased weight and waist circumference over the days. The volume of peritoneal ascitic fluid was lower in the Morf5, Morf10 treatments and in all tested methadone doses compared to the Saline group. Viability and number of total cells did not differ between treatments. Morf10 and Met5,7 treatments interfered in the cell cycle of tumor cells, with a higher percentage of cells in the G1 phase of the cycle, compared to the Saline group. It was observed, from the first experiment, that all doses tested promote increased locomotion and reduced exploratory behaviors that were more evident over the treatment days. Antinociception was observed for up to 40 minutes in a single dose and continued for up to 150 minutes after serial administrations in intermediate and higher doses. The Morf10 and Met5,7 treatments promoted cell cycle stasis, but did not significantly interfere with the growth of Ehrlich\'s ascites tumor
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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