Human and rat microsomal metabolites of N-tert-butoxycarbonylmethamphetamine and its urinary metabolites in rat.

PURPOSE: N-tert-Butoxycarbonylmethamphetamine (BocMA), a masked derivative of methamphetamine (MA), converts into MA under acidic condition and potentially acts as a precursor to MA following ingestion. To investigate the metabolism and excretion of BocMA, metabolism tests were conducted using human liver microsomes (HLM), rat liver microsomes (RLM) and rat. METHODS: BocMA metabolites were analyzed after 1000-ng/mL BocMA incubation with microsomes for 3, 8, 13, 20, 30, and 60 min. Rats were administered intraperitoneal injections (20 mg/kg) of BocMA and their urine was collected in intervals for 72 h. Metabolites were detected by liquid chromatography-tandem mass spectrometry with five authentic standards. RESULTS: Several metabolites including 4-hydroxy-BocMA, N-tert-butoxycarbonylephedrine and N-tert-butoxycarbonyl-cathinone were detected for HLM and RLM. In the administration test, three glucuronides of hydroxylated metabolites were detected. The total recovery values of BocMA and the metabolites during the first 72 h accounted for only 0.3% of the administered dose. Throughout the microsomal and administration experiments, MAs were not detected. CONCLUSION: Hydroxylation, carbonylation and N-demethylation were proposed as metabolic pathways. However, BocMA and phase I metabolites were hardly detected in urine. This study provides useful information to interpret the possibility of BocMA intake as the cause of MA detection in biological sample.

Intradural extramedullary hemangioblastoma of the thoracic cord: A case report.

BACKGROUND: Spinal hemangioblastomas account for 1-3% of all spinal cord tumors and are mostly intramedullary in location. Here, we report an intradural extramedullary hemangioblastoma of the thoracic spine, occurring in in a patient without von Hippel-Lindau disease. CASE DESCRIPTION: A 58-year-old female had a 5-year history of progressive left lower extremity weakness. When the MR demonstrated an intradural/extramedullary lesion with a syrinx at the T2-3 level, she successfully underwent gross total tumor excision following which she neurologically improved. CONCLUSION: Here, we report a rare case of an intradural/extramedullary thoracic hemangioblastoma successfully excised at the T 2-3 level in a patient without von Hippel-Lindau disease.

Disruption of Kir6.2-containing ATP-sensitive potassium channels impairs maintenance of hypoxic gasping in mice.

Hypoxic gasping emerges under severe hypoxia/ischemia in various species, exerting a life-protective role by assuring minimum ventilation even in loss of consciousness. However, the molecular basis of its generation and maintenance is not well understood. Here we found that mice lacking Kir6.2- but not Kir6.1-containing ATP-sensitive potassium (K(ATP)) channels [knockout (KO) mice] exhibited few gaSPS when subjected to abrupt ischemia by decapitation, whereas wild-type mice all exhibited more than 10 gaSPS. Under anesthesia, wild-type mice initially responded to severe hypoxic insult with augmented breathing (tachypnea) accompanied by sighs and subsequent depression of respiratory frequency. Gasping then emerged and persisted stably (persistent gasping); if the hypoxia continued, several gaSPS with distinct patterns appeared (terminal gasping) before cessation of breathing. KO mice showed similar hypoxic responses but both depression and the two types of gasping were of much shorter duration than in wild-type mice. Moreover, in the unanesthetized condition, the onset of terminal gasping in KO mice, which was always earlier than in wild-type mice, was unaltered by decreasing O(2) concentrations within the severe range (4.5-7.0%), whereas onset in wild-type mice became earlier in response to lowered O(2) concentrations. Thus, the mechanism responsible for regulating the hypoxic response in accordance with the severity of the hypoxia was dysfunctional in these KO mice, suggesting that Kir6.2-containing K(ATP) channels are critically involved in the maintenance rather than the generation of hypoxic gasping and depression of respiratory frequency.