RESUMEN
Fenitrothion is one of the most globally used organophosphorus pesticides, which can cause neurological symptoms, including involuntary movements. However, due to the limited number of case report, information on its treatment is also scarce. Here we presented a 74-year-old Japanese woman who was admitted to our hospital due to a persistent nausea and vomiting after ingesting 200 mL of 50% fenitrothion for a suicidal attempt. She received continuous intravenous infusion of atropine and 2-pyridine aldoxime methiodide under mechanical ventilation and continuous hemodiafiltration. However, she developed fasciculations of the face and right arm on day 11, which raised suspicions of delayed neuropathy associated with organophosphorus poisoning. To reduce the risk of respiratory depression, she received intravenous levetiracetam at a dosage of 1,000 mg/day. However, as her fasciculations persisted, the levetiracetam dosage was adjusted to 2,000 mg/day on day 14. On the following day, her fasciculations subsided. Neurologic symptoms of lipid-soluble organophosphorus poisoning, including fenitrothion, can sometimes delay following ingestion. Temporary administration of levetiracetam may prove effective in alleviating fasciculations.
RESUMEN
SP7/Osterix (OSX) is a master regulatory transcription factor that activates a variety of genes during differentiation of osteoblasts. However, the influence of post-translational modifications on the regulation of its transactivation activity is largely unknown. Here, we report that sirtuins, which are NAD(+)-dependent deacylases, regulate lysine deacylation-mediated transactivation of OSX. Germline Sirt7 knockout mice develop severe osteopenia characterized by decreased bone formation and an increase of osteoclasts. Similarly, osteoblast-specific Sirt7 knockout mice showed attenuated bone formation. Interaction of SIRT7 with OSX leads to the activation of transactivation by OSX without altering its protein expression. Deacylation of lysine (K) 368 in the C-terminal region of OSX by SIRT7 promote its N-terminal transactivation activity. In addition, SIRT7-mediated deacylation of K368 also facilitates depropionylation of OSX by SIRT1, thereby increasing OSX transactivation activity. In conclusion, our findings suggest that SIRT7 has a critical role in bone formation by regulating acylation of OSX.
