ABSTRACT
Isobutyl nitrite is one of the popular recreational drugs with high abuse potential that is known to cause methemoglobinemia. While inhaling this recreational drug, often referred to as a 'popper', is the typical route of administration, oral ingestion can produce a more rapid and fulminant course of methemoglobinemia. We present the case of a 69-year-old male that presented to our emergency department in extreme, life-threatening methemoglobinemia due to the ingestion of isobutyl nitrite that he obtained from an adult novelty store. The patient had a methemoglobin level above our lab cut-off of 28% and was subsequently treated with two doses of intravenous methylene blue. His hospital course was unremarkable, and he was discharged on Day 2. Methemoglobinemia is a medical emergency that requires a high index of clinical suspicion, prompt recognition, and rapid treatment.
ABSTRACT
Ocular neovascularization underlies major blinding eye diseases such as "wet" age-related macular degeneration (AMD). Despite the successes of treatments targeting the vascular endothelial growth factor (VEGF) pathway, resistant and refractory patient populations necessitate discovery of new therapeutic targets. Using a forward chemical genetic approach, we identified the heme synthesis enzyme ferrochelatase (FECH) as necessary for angiogenesis in vitro and in vivo FECH is overexpressed in wet AMD eyes and murine choroidal neovascularization; siRNA knockdown of Fech or partial loss of enzymatic function in the Fechm1Pas mouse model reduces choroidal neovascularization. FECH depletion modulates endothelial nitric oxide synthase function and VEGF receptor 2 levels. FECH is inhibited by the oral antifungal drug griseofulvin, and this compound ameliorates choroidal neovascularization in mice when delivered intravitreally or orally. Thus, FECH inhibition could be used therapeutically to block ocular neovascularization.
