N400 in schizophrenia patients.

PURPOSE OF REVIEW: The purpose of this article is to review major findings in event related potential (ERP) research in schizophrenia patients, specifically focusing on the N400 component. RECENT FINDINGS: Patients with chronic schizophrenia have difficulty using 'context' (understanding the meaning of the word relative to the sentence) in sentence processing studies and often show differences from control populations in language experiments using word priming. Both of these observations are associated with an abnormal N400 ERP component when compared with nonpsychotic individuals. Many studies of language function rely on priming paradigms that use pairs of words such that the first word in a pair is a 'prime' and a second word in a pair is a 'target', separated from the prime by a period of time known as the Stimulus Onset Asynchrony (SOA). If the SOA is short (i.e., below 400 ms) then it is believed that a priming study examines primarily processes of initial activation within semantic networks; if it is long (i.e., more than 400 ms) then it is believed that a priming study examines primarily processes of context use, generating predictions and matching these predictions against upcoming semantic information. Priming paradigms that use long SOAs are consistently associated with a more negative N400 (hence lack of priming) in schizophrenia, whereas priming paradigms using a short SOA produce either a normal N400 priming response or hyperpriming as shown by a reduced N400 and related to a hypothesized too rapid automatic spread of activation within the semantic memory pathway. Apparent differences among reported study results are likely due to paradigm differences that tap into different aspects of language processing. Although the presence of both hyperactivation within semantic networks and difficulties with the use of context is well known in schizophrenia, it is unclear whether these abnormalities are also present prior to illness onset in people who are at risk for development of schizophrenia or even present at the onset of illness. SUMMARY: In order to clarify the findings reviewed here, future studies will be needed that focus on examining the N400 response in young people at high risk for developing the illness using multiple paradigms that probe different aspects of language function.

Cobinamide is superior to other treatments in a mouse model of cyanide poisoning.

CONTEXT: Cyanide is a rapidly acting cellular poison, primarily targeting cytochrome c oxidase, and is a common occupational and residential toxin, mostly via smoke inhalation. Cyanide is also a potential weapon of mass destruction, with recent credible threats of attacks focusing the need for better treatments, as current cyanide antidotes are limited and impractical for rapid deployment in mass casualty settings. OBJECTIVE: We have used mouse models of cyanide poisoning to compare the efficacy of cobinamide (Cbi), the precursor to cobalamin (vitamin B(12)), to currently approved cyanide antidotes. Cbi has extremely high affinity for cyanide and substantial solubility in water. MATERIALS AND METHODS: We studied Cbi in both an inhaled and intraperitoneal model of cyanide poisoning in mice. RESULTS: We found Cbi more effective than hydroxocobalamin, sodium thiosulfate, sodium nitrite, and the combination of sodium thiosulfate-sodium nitrite in treating cyanide poisoning. Compared to hydroxocobalamin, Cbi was 3 and 11 times more potent in the intraperitoneal and inhalation models, respectively. Cobinamide sulfite (Cbi-SO(3)) was rapidly absorbed after intramuscular injection, and mice recovered from a lethal dose of cyanide even when given at a time when they had been apneic for over 2 min. In range-finding studies, Cbi-SO(3) at doses up to 2000 mg/kg exhibited no clinical toxicity. DISCUSSION AND CONCLUSION: These studies demonstrate that Cbi is a highly effective cyanide antidote in mouse models, and suggest it could be used in a mass casualty setting, because it can be given rapidly as an intramuscular injection when administered as Cbi-SO(3). Based on these animal data Cbi-SO(3) appears to be an antidote worthy of further testing as a therapy for mass casualties.