RESUMO
RATIONALE AND OBJECTIVES: Liver inflammation is associated with nonalcoholic steatohepatitis and other pathologies, but noninvasive methods to assess liver inflammation are limited. Inflammation causes endothelial disruption and leakage of plasma proteins into the interstitial space and can result in extravascular coagulation with fibrin deposition. Here we assess the feasibility of using the established fibrin-specific magnetic resonance probe EP-2104R for the noninvasive imaging of fibrin as a marker of liver inflammation. METHODS: Weekly 100 mg/kg diethylnitrosamine (DEN) dosing was used to generate liver fibrosis in male rats; control animals received vehicle. Magnetic resonance imaging at 1.5 T with EP-2104R, a matched non-fibrin-binding control linear peptide, or the collagen-specific probe EP-3533 was performed at 1 day or 7 days after the last DEN administration. Imaging data were compared with quantitative histological measures of fibrosis and inflammation. RESULTS: After 4 or 5 DEN administrations, the liver becomes moderately fibrotic, and fibrosis is the same if the animal is killed 1 day (Ishak score, 3.62 ± 0.31) or 7 days (Ishak score, 3.82 ± 0.25) after the last DEN dose, but inflammation is significantly higher at 1 day compared with 7 days after the last DEN dose (histological activity index from 0-4, 3.54 ± 0.14 vs 1.61 ± 0.16, respectively; P < 0.0001). Peak EP-2104R signal enhancement was significantly higher in animals imaged at 1 day post-DEN compared with 7 days post-DEN or control rats (29.0% ± 3.2% vs 22.4% ± 2.0% vs 17.0% ± 0.2%, respectively; P = 0.017). Signal enhancement with EP-2104R was significantly higher than control linear peptide at 1 day post-DEN but not at 7 days post-DEN indicating specific fibrin binding during the inflammatory phase. Collagen molecular magnetic resonance with EP-3533 showed equivalent T1 change when imaging rats 1 day or 7 days post-DEN, consistent with equivalent fibrosis. CONCLUSIONS: EP-2104R can specifically detect fibrin associated with inflammation in a rat model of liver inflammation and fibrosis.
Assuntos
Fibrina/metabolismo , Inflamação/diagnóstico , Inflamação/patologia , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Imageamento por Ressonância Magnética/métodos , Animais , Modelos Animais de Doenças , Gadolínio , Inflamação/metabolismo , Fígado/diagnóstico por imagem , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/metabolismo , Masculino , Peptídeos , Ratos , Ratos WistarRESUMO
Advances in technology and imaging techniques have propelled radiology into the centre of diagnostic and therapeutic medicine. However, all this success has come at a price, with radiology departments persistently struggling to keep up with increasing demand. In response, radiologists in many countries are giving up an increasing proportion of their traditional workload, often driven by teleradiology, causing them to become less visible within their organizations. As such, radiologists now risk being viewed as commodities by their peers. The failure to meet the increasing stakeholder expectations is, at least in part, due to lack of radiology leadership. While the drivers for the radiology profession and the organizational structures for radiologists vary from country to country, this article will discuss the characteristics of good leadership and how these can be used to ensure radiologists remain centre stage in the provision of high-quality clinical care in any healthcare environment.
Assuntos
Liderança , Serviços Terceirizados/organização & administração , Serviço Hospitalar de Radiologia/organização & administração , Radiologia/organização & administração , Telerradiologia/organização & administração , Estados UnidosAssuntos
Clozapina/efeitos adversos , Colo/patologia , Motilidade Gastrointestinal/efeitos dos fármacos , Megacolo Tóxico/diagnóstico , Antagonistas da Serotonina/efeitos adversos , Abdome/patologia , Dor Abdominal/etiologia , Doença Aguda , Adulto , Transtornos da Coagulação Sanguínea/etiologia , Colo/diagnóstico por imagem , Colo/cirurgia , Diagnóstico Diferencial , Dilatação Patológica/etiologia , Humanos , Masculino , Megacolo Tóxico/etiologia , Megacolo Tóxico/cirurgia , Radiografia , Esquizofrenia Paranoide/complicações , Esquizofrenia Paranoide/tratamento farmacológico , Choque Séptico/etiologiaAssuntos
Coccidioidomicose/diagnóstico , Transplante de Rim , Rim/patologia , Biópsia por Agulha , Coccidioidomicose/complicações , Confusão/etiologia , Cetoacidose Diabética/etiologia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Pulmão/diagnóstico por imagem , Pulmão/patologia , Pneumopatias Fúngicas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Necrose , Infecções Oportunistas/complicações , Infecções Oportunistas/diagnóstico , Insuficiência Renal/etiologia , Tomografia Computadorizada por Raios XAssuntos
Atenção à Saúde/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Gastos em Saúde/estatística & dados numéricos , Radiologia/economia , Radiologia/estatística & dados numéricos , Tomografia Computadorizada por Raios X/economia , Tomografia Computadorizada por Raios X/estatística & dados numéricos , Análise Custo-Benefício , Atenção à Saúde/estatística & dados numéricos , Europa (Continente) , Custos de Cuidados de Saúde/tendências , Gastos em Saúde/tendências , Radiologia/tendênciasRESUMO
Prostate cancer is the second leading cause of cancer-related deaths in men. Activation of MAP kinase signaling pathway has been implicated in advanced and androgen-independent prostate cancers, although formal genetic proof has been lacking. In the course of modeling malignant melanoma in a tyrosinase promoter transgenic system, we developed a genetically-engineered mouse (GEM) model of invasive prostate cancers, whereby an activating mutation of BRAF(V600E)--a mutation found in approximately 10% of human prostate tumors--was targeted to the epithelial compartment of the prostate gland on the background of Ink4a/Arf deficiency. These GEM mice developed prostate gland hyperplasia with progression to rapidly growing invasive adenocarcinoma without evidence of AKT activation, providing genetic proof that activation of MAP kinase signaling is sufficient to drive prostate tumorigenesis. Importantly, genetic extinction of BRAF(V600E) in established prostate tumors did not lead to tumor regression, indicating that while sufficient to initiate development of invasive prostate adenocarcinoma, BRAF(V600E) is not required for its maintenance.