Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
JACC Cardiovasc Imaging ; 11(2 Pt 2): 291-301, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29413439

RESUMO

OBJECTIVES: The authors sought to develop combined positron emission tomography (PET) dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) to quantify plaque inflammation, permeability, and burden to evaluate the efficacy of a leukotriene A4 hydrolase (LTA4H) inhibitor in a rabbit model of atherosclerosis. BACKGROUND: Multimodality PET/MRI allows combining the quantification of atherosclerotic plaque inflammation, neovascularization, permeability, and burden by combined 18F-fluorodeoxyglucose (18F-FDG) PET, DCE-MRI, and morphological MRI. The authors describe a novel, integrated PET-DCE/MRI protocol to noninvasively quantify these parameters in aortic plaques of a rabbit model of atherosclerosis. As proof-of-concept, the authors apply this protocol to assess the efficacy of the novel LTA4H inhibitor BI691751. METHODS: New Zealand White male rabbits (N = 49) were imaged with integrated PET-DCE/MRI after atherosclerosis induction and 1 and 3 months after randomization into 3 groups: 1) placebo; 2) high-dose BI691751; and 3) low-dose BI691751. All animals were euthanized at the end of the study. RESULTS: Among the several metrics that were quantified, only maximum standardized uptake value and target-to-background ratio by 18F-FDG PET showed a modest, but significant, reduction in plaque inflammation in rabbits treated with low-dose BI691751 (p = 0.03), whereas no difference was detected in the high-fat diet and in the high-dose BI691751 groups. No differences in vessel wall area by MRI and area under the curve by DCE-MRI were detected in any of the groups. No differences in neovessel and macrophage density were found at the end of study among groups. CONCLUSIONS: The authors present a comprehensive, integrated 18F-FDG PET and DCE-MRI imaging protocol to noninvasively quantify plaque inflammation, neovasculature, permeability, and burden in a rabbit model of atherosclerosis on a simultaneous PET/MRI scanner. A modest reduction was found in plaque inflammation by 18F-FDG PET in the group treated with a low dose of the LTA4H inhibitor BI691751.


Assuntos
Anti-Inflamatórios/farmacologia , Doenças da Aorta/tratamento farmacológico , Aterosclerose/tratamento farmacológico , Permeabilidade Capilar/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Epóxido Hidrolases/antagonistas & inibidores , Inflamação/tratamento farmacológico , Imageamento por Ressonância Magnética , Placa Aterosclerótica , Tomografia por Emissão de Pósitrons , Animais , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/enzimologia , Doenças da Aorta/patologia , Aterosclerose/diagnóstico por imagem , Aterosclerose/enzimologia , Aterosclerose/patologia , Biomarcadores/sangue , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Epóxido Hidrolases/metabolismo , Fluordesoxiglucose F18/administração & dosagem , Gadolínio DTPA/administração & dosagem , Inflamação/diagnóstico por imagem , Inflamação/enzimologia , Inflamação/patologia , Masculino , Imagem Multimodal , Valor Preditivo dos Testes , Coelhos , Compostos Radiofarmacêuticos/administração & dosagem
2.
Arthritis Rheum ; 63(9): 2641-50, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21567377

RESUMO

OBJECTIVE: Blood C-reactive protein (CRP) is routinely measured to gauge inflammation. In rheumatoid arthritis (RA), a heightened CRP level is predictive of a poor outcome, while a lowered CRP level is indicative of a positive response to therapy. CRP interacts with the innate and adaptive immune systems in ways that suggest it may be causal in RA and, although this is not proven, it is widely assumed that CRP makes a detrimental contribution to the disease process. Paradoxically, results from animal studies have indicated that CRP might be beneficial in RA. This study was undertaken to study the role of CRP in a mouse model of RA, the collagen-induced arthritis (CIA) model. METHODS: We compared the impact of CRP deficiency with that of transgenic overexpression of CRP on inflammatory and immune responses in mice, using CRP-deficient (Crp-/-) and human CRP-transgenic (CRP-Tg) mice, respectively. Susceptibility to CIA, a disease that resembles RA in humans, was compared between wild-type, Crp-/-, and CRP-Tg mice. RESULTS: CRP deficiency significantly altered the inflammatory cytokine response evoked by challenge with endotoxin or anti-CD3 antibody, and heightened some immune responses. Compared to that in wild-type mice, CIA in Crp-/- mice progressed more rapidly and was more severe, whereas CIA in CRP-Tg mice was dramatically attenuated. Despite these disparate clinical outcomes, anticollagen autoantibody responses during CIA did not differ among the genotypes. CONCLUSION: CRP exerts an early and beneficial effect in mice with CIA. The mechanism of this effect remains unknown but does not involve improvement of the autoantibody profile. In humans, the presumed detrimental role of a heightened blood CRP level during active RA might be balanced by a beneficial effect of the baseline CRP (i.e., levels manifest during the preclinical stages of disease).


Assuntos
Artrite Experimental/genética , Proteína C-Reativa/genética , Citocinas/imunologia , Inflamação/imunologia , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Modelos Animais de Doenças , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Índice de Gravidade de Doença
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...