RESUMO
Decreased cerebral blood flow (CBF) may contribute to the pathology of multiple sclerosis (MS), but the underlying mechanism is unknown. We investigated whether the potent vasoconstrictor endothelin-1 (ET-1) is involved. We found that, compared with controls, plasma ET-1 levels in patients with MS were significantly elevated in blood drawn from the internal jugular vein and a peripheral vein. The jugular vein/peripheral vein ratio was 1.4 in patients with MS vs. 1.1 in control subjects, suggesting that, in MS, ET-1 is released from the brain to the cerebral circulation. Next, we performed ET-1 immunohistochemistry on postmortem white matter brain samples and found that the likely source of ET-1 release are reactive astrocytes in MS plaques. We then used arterial spin-labeling MRI to noninvasively measure CBF and assess the effect of the administration of the ET-1 antagonist bosentan. CBF was significantly lower in patients with MS than in control subjects and increased to control values after bosentan administration. These data demonstrate that reduced CBF in MS is mediated by ET-1, which is likely released in the cerebral circulation from reactive astrocytes in plaques. Restoring CBF by interfering with the ET-1 system warrants further investigation as a potential new therapeutic target for MS.
Assuntos
Astrócitos/metabolismo , Circulação Cerebrovascular/efeitos dos fármacos , Endotelina-1/antagonistas & inibidores , Esclerose Múltipla/fisiopatologia , Sulfonamidas/farmacologia , Bosentana , Circulação Cerebrovascular/fisiologia , Endotelina-1/sangue , Endotelina-1/metabolismo , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Esclerose Múltipla/tratamento farmacológico , Marcadores de Spin , Estatísticas não ParamétricasRESUMO
BACKGROUND: Only 13 cases of pyomyoma related to pregnancy have been described since 1945. Treatment consists of hysterectomy, which exposes critically ill patients to operative risks and induces infertility. CASES: Three cases of pyomyoma in the postpartum period are described. Treatment using computed tomography-guided drainage was realized successfully in two cases. CONCLUSION: Therapy via drainage and lavage of pyomyoma is a viable option to preserve patient fertility. In the absence of a proper response to this treatment, total abdominal hysterectomy is the treatment of choice.