RESUMO
Endothelial dysfunction reflects reduced nitric oxide (NO) bioavailability due to either reduced production, inactivation of NO, or reduced smooth muscle responsiveness. Oral methionine loading causes acute endothelial dysfunction in healthy subjects and provides a model in which to study mechanisms. Endothelial function was assessed using flow-mediated dilatation (FMD) of the brachial artery in humans. Three markers of oxidative stress were measured ex vivo in venous blood. NO responsiveness was assessed in vascular smooth muscle and platelets. Oral methionine loading induced endothelial dysfunction (FMD decreased from 2.8 +/- 0.8 to 0.3 +/- 0.3% with methionine and from 2.8 +/- 0.8 to 1.3 +/- 0.3% with placebo; P < 0.05). No significant changes in measures of plasma oxidative stress or in vascular or platelet sensitivity to submaximal doses of NO donors were detected. These data suggest that oxidative stress is not the mechanism of endothelial dysfunction after oral methionine loading. Furthermore, the preservation of vascular and platelet NO sensitivity makes a signal transduction abnormality unlikely.
Assuntos
Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Metionina , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Idoso , Artéria Braquial/metabolismo , Estudos Cross-Over , Homocisteína/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Masculino , Pessoa de Meia-Idade , Nitratos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Estudos Prospectivos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
The testis and central nervous system (CNS) may act as sanctuary sites for testicular germ cell tumours, as cytotoxic drugs penetrate these areas less well than systemic sites. We describe three patients who relapsed in the testis (one patient) or CNS (two patients) after receiving chemotherapy for responsive systemic disease. All three were asymptomatic at relapse, which was first manifest by rising tumour marker levels. These sanctuary site relapses were managed locally with surgery +/- radiotherapy. Two patients were rendered disease-free; one died of progression of his local disease only. Sanctuary site tumour should be considered when relapse occurs in the setting of otherwise chemosensitive disease; local therapy may be curative.