1,720,957 research outputs found
Heme oxigenase-1 como um alvo terapêutico na sepse o papel da biliverdina
No full textFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, BrasilA heme oxigenase-1 (HO-1), uma enzima induzida sob diversas condições de estresse celular, cataboliza o heme em monóxido de carbono (CO), biliverdina (convertida posteriormente a bilirrubina) e ferro livre. A deficiência dessa enzima resulta em inflamação crônica e morte prematura. Por outro lado, o aumento da HO-1 e de seus produtos resulta em efeitos antiinflamatórios e antioxidantes. As injúrias inflamatória e oxidativa desempenham um papel importante na fisiopatologia da sepse. Nesse contexto, a HO-1 vem sendo caracterizada como um gene protetor. Recentemente, estudos demonstraram que a indução da HO-1 ou a terapia com o CO e a biliverdina, isoladamente ou em associação, são capazes de diminuir a disfunção orgânica e a mortalidade em modelos animais de endotoxemia letal. Nossa proposta foi estudar o efeito da modulação da HO-1 e do tratamento com a biliverdina em um modelo mais clinicamente relevante de sepse, a ligadura e perfuração cecal (CLP). Nossos resultados apontam para um efeito benéfico da HO-1 no tratamento da sepse. Demonstramos que o tratamento com a estanho protoporfirina (SnPP), um supressor da HO-1, aumenta a mortalidade da CLP. Já nos animais tratados com a cobalto protoporfirina (CoPP), um indutor da HO-1, há um aumento da sobrevida. O tratamento com a biliverdina também teve um impacto significativo, tanto em um modelo de endotoxemia letal como no modelo de CLP, reduzindo a mortalidade em aproximadamente 60% e 40%, respectivamente. Esse efeito protetor observado na CLP foi associado a uma modulação da resposta inflamatória, constatada pela redução do acúmulo de leucócitos e dos níveis de mediadores inflamatórios (TNF-a, IL-6, KC e IL-10) na cavidade peritoneal. Ao mesmo tempo, os animais tratados com a biliverdina apresentaram um decréscimo no número de unidades formadoras de colônias no lavado peritoneal, sugerindo um melhor controle local da infecção.Heme oxygenase-1 (HO-1), an enzyme induced under va
rious situations of cellular stress,
catabolyses heme into carbon monoxide (CO), biliver
din (subsequently converted to
bilirubin) and free iron. The deficiency of this en
zyme results in chronic inflammation and
premature death. On the other hand, an increase in
HO-1 and its products results in anti-
inflammatory and antioxidant effects. Inflammatory
and oxidative injuries play an
important role in sepsis pathophysiology. In this c
ontext, HO-1 has been characterized as a
protective gene. Recently, studies have shown that
the induction of HO-1 or therapy with
CO and biliverdin, isolated or in association, is c
apable of reducing organic dysfunction and
mortality in animal models of lethal endotoxemia. O
ur goal was to study the effects of the
modulation of HO-1 and the treatment with biliverdi
n in a more clinically relevant model of
sepsis, the cecal ligation and puncture (CLP) model
. Our results suggest a beneficial effect
of HO-1 in sepsis treatment. We demonstrated that t
he treatment with tin protoporphyrin
(SnPP), a suppressor of HO-1, increases CLP mortali
ty. On the other hand, animals treated
with cobalt protoporphyrin (CoPP), an inducer of HO
-1, had an increased survival.
Treatment with biliverdin also had a significant im
pact over both lethal endotoxemia and
CLP, reducing mortality in approximately 60% and 40
%, respectively. This protective
effect of biliverdin on CLP was associated with a m
odulation of the inflammatory response,
observed by the reduction of leukocyte accumulation
and levels of inflammatory mediators
(TNF, IL-6, KC and IL-10) in the peritoneal cavity.
At the same time, the animals treated
with biliverdin had decreased numbers of colony-for
ming units in the peritoneal lavage
fluid, suggesting a better local control of infecti
o
Análise do Fenótipo Imunometabólico de Monócitos na Sepse
No full textA sepse representa um desafio para os sistemas de saúde em todo o mundo, pela sua elevada incidência, mortalidade e custos associados. O evento fundamental para o desenvolvimento da sepse parece ser a desregulação e perda do direcionamento da resposta inflamatória, podendo resultar em estados hiperinflamatórios ou de imunossupressão, com reflexos patológicos sistêmicos. No entanto, o mecanismo através do qual esta disfunção imunológica se estabelece ainda permanece em grande parte obscuro, e nenhum agente imunomodulatório se encontra disponível para o tratamento clínico da sepse. As células da linhagem monocítica fagocitária são agentes essenciais na resposta inicial à infeção. Um conjunto crescente de evidências aponta para uma relação de interdependência entre o metabolismo e o estado de ativação imune dessas células. Ao mesmo tempo, estudos prévios sugerem que uma disfunção bioenergética de leucócitos na sepse poderia prejudicar a formação de uma resposta imune efetiva, associando-se a desfechos clínicos desfavoráveis. Nos estudos que compõem esta tese, procuramos caracterizar o fenótipo imunometabólico de monócitos na sepse Demonstramos em experimentos in vitro que macrófagos e monócitos ativados apresentam um intenso aumento da atividade glicolítica, que passa a ser a principal fonte geradora de ATP celular, acompanhado de uma redução da fosforilação oxidativa. Em seguida, estabelecemos uma coorte prospectiva para caracterizar o proteoma dos monócitos do sangue periférico, comparando quantitativamente amostras de doadores saudáveis às de pacientes na fase aguda da sepse e na fase de recuperação. Utilizando uma abordagem de proteômica exploratória, nossos dados evidenciaram que, de forma semelhante ao observado nos modelos experimentais, a transição para a glicólise é uma característica proeminente na fase aguda da sepse. Além disso, o perfil da coorte foi inicialmente sugestivo de imunossupressão, sendo sucedido na fase de recuperação pela restauração da imunocompetência, o que foi documentado pela regulação diferencial de proteínas envolvidas na apresentação de antígenos, como o HLA-DR, e sinalização por citocinas, particularmente o IFN-\0263. Avaliamos também a aplicabilidade de uma metodologia de proteômica dirigida para a verificação e aprofundamento da investigação das alterações observadas. Nosso estudo sugere que as vias do metabolismo energético podem ter um papel relevante na imunopatogênese da sepse.Sepsis represents a challenge for healthcare systems around the world due to its high incidence, mortality, and associated costs. The fundamental event for the development of sepsis seems to be the deregulation and loss of directionality of the inflammatory response, which may result in hyperinflammatory or immunosuppressive states, with systemic pathological reflexes. However, the mechanism by which this immunological dysfunction is established remains largely obscure, and no immunomodulatory agent is available for the clinical treatment of sepsis. Mononuclear phagocyte system cell lines are essential agents in the initial response to infection. A growing body of evidence points to a relationship of interdependence between the metabolism and the immune activation state of these cells. At the same time, previous studies have suggested that a bioenergetic dysfunction of leukocytes in sepsis could impair the formation of an effective immune response, associated with unfavorable clinical outcomes. In the studies that compose this thesis, we sought to characterize the immunometabolic phenotype of monocytes in sepsis We demonstrated using in vitro experiments that activated macrophages and monocytes present an intense increase of glycolytic activity, which becomes the main source of cellular ATP, accompanied by a reduction of oxidative phosphorylation. Next, we established a prospective cohort to characterize the proteome of peripheral blood monocytes, comparing quantitatively healthy donor samples to those of patients in the acute phase of sepsis and in the recovery phase. Using an exploratory proteomics approach, our data showed that, similar to that observed in the experimental models, the shift to glycolysis is a prominent feature in the acute phase of sepsis. In addition, the cohort profile was initially suggestive of immunosuppression, being succeeded by the restoration of immunocompetence in the recovery phase, which was documented by the differential regulation of proteins involved in the presentation of antigens, such as HLA-DR, and cytokine signaling, particularly IFN-\0263. We also evaluated the applicability of a targeted proteomics methodology to verify and deepen the investigation of the observed changes. Our study suggests that energetic metabolic pathways may play a relevant role in the immunopathogenesis of sepsis
Heme oxigenase-1 como um alvo terapêutico na sepse o papel da biliverdina
No full textA heme oxigenase-1 (HO-1), uma enzima induzida sob diversas condições de estresse celular, cataboliza o heme em monóxido de carbono (CO), biliverdina (convertida posteriormente a bilirrubina) e ferro livre. A deficiência dessa enzima resulta em inflamação crônica e morte prematura. Por outro lado, o aumento da HO-1 e de seus produtos resulta em efeitos antiinflamatórios e antioxidantes. As injúrias inflamatória e oxidativa desempenham um papel importante na fisiopatologia da sepse. Nesse contexto, a HO-1 vem sendo caracterizada como um gene protetor. Recentemente, estudos demonstraram que a indução da HO-1 ou a terapia com o CO e a biliverdina, isoladamente ou em associação, são capazes de diminuir a disfunção orgânica e a mortalidade em modelos animais de endotoxemia letal. Nossa proposta foi estudar o efeito da modulação da HO-1 e do tratamento com a biliverdina em um modelo mais clinicamente relevante de sepse, a ligadura e perfuração cecal (CLP). Nossos resultados apontam para um efeito benéfico da HO-1 no tratamento da sepse. Demonstramos que o tratamento com a estanho protoporfirina (SnPP), um supressor da HO-1, aumenta a mortalidade da CLP. Já nos animais tratados com a cobalto protoporfirina (CoPP), um indutor da HO-1, há um aumento da sobrevida. O tratamento com a biliverdina também teve um impacto significativo, tanto em um modelo de endotoxemia letal como no modelo de CLP, reduzindo a mortalidade em aproximadamente 60% e 40%, respectivamente. Esse efeito protetor observado na CLP foi associado a uma modulação da resposta inflamatória, constatada pela redução do acúmulo de leucócitos e dos níveis de mediadores inflamatórios (TNF-a, IL-6, KC e IL-10) na cavidade peritoneal. Ao mesmo tempo, os animais tratados com a biliverdina apresentaram um decréscimo no número de unidades formadoras de colônias no lavado peritoneal, sugerindo um melhor controle local da infecção.Heme oxygenase-1 (HO-1), an enzyme induced under va
rious situations of cellular stress,
catabolyses heme into carbon monoxide (CO), biliver
din (subsequently converted to
bilirubin) and free iron. The deficiency of this en
zyme results in chronic inflammation and
premature death. On the other hand, an increase in
HO-1 and its products results in anti-
inflammatory and antioxidant effects. Inflammatory
and oxidative injuries play an
important role in sepsis pathophysiology. In this c
ontext, HO-1 has been characterized as a
protective gene. Recently, studies have shown that
the induction of HO-1 or therapy with
CO and biliverdin, isolated or in association, is c
apable of reducing organic dysfunction and
mortality in animal models of lethal endotoxemia. O
ur goal was to study the effects of the
modulation of HO-1 and the treatment with biliverdi
n in a more clinically relevant model of
sepsis, the cecal ligation and puncture (CLP) model
. Our results suggest a beneficial effect
of HO-1 in sepsis treatment. We demonstrated that t
he treatment with tin protoporphyrin
(SnPP), a suppressor of HO-1, increases CLP mortali
ty. On the other hand, animals treated
with cobalt protoporphyrin (CoPP), an inducer of HO
-1, had an increased survival.
Treatment with biliverdin also had a significant im
pact over both lethal endotoxemia and
CLP, reducing mortality in approximately 60% and 40
%, respectively. This protective
effect of biliverdin on CLP was associated with a m
odulation of the inflammatory response,
observed by the reduction of leukocyte accumulation
and levels of inflammatory mediators
(TNF, IL-6, KC and IL-10) in the peritoneal cavity.
At the same time, the animals treated
with biliverdin had decreased numbers of colony-for
ming units in the peritoneal lavage
fluid, suggesting a better local control of infecti
o
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
- …
