A superoxide dismutase mimetic with catalase activity (EUK-8) reduces the organ injury in endotoxic shock

Reactive oxygen species contribute to the multiple organ failure in endotoxic shock. Here, we investigate the effects of a salen-manganese complex, which exhibits both superoxide dismutase and catalase activity (EUK-8), on the circulatory failure, renal and liver injury and dysfunction caused by endotoxin in the anaesthetised rat. Endotoxaemia (6 mg/kg i.v., Escherichia coli lipopolysaccharide) for 6 h caused hypotension, renal dysfunction and liver injury. Treatment of rats with EUK-8 (0.3 or 1 mg/kg bolus injection followed by an infusion of 0.3 or 1 mg/kg/h) attenuated the renal and liver injury and dysfunction in a dose-related fashion. In addition, the higher dose of EUK-8 attenuated the delayed hypotension caused by endotoxin in the rat. Thus, an enhanced formation of reactive oxygen species importantly contributes to the circulatory failure, as well as the organ injury and dysfunction associated with endotoxic shock. We propose that small molecules, which have the catalytic activity of both superoxide dismutase and catalase, may represent a novel therapeutic approach for the therapy of endotoxic shock

Treatment consideration and manifest complexity in comorbid neuropsychiatric disorders

Psychiatric disorders may co-occur in the same individual. These include, for example, substance abuse or obsessive-compulsive disorder with schizophrenia, and movement disorders or epilepsy with affective dysfunctional states. Medications may produce iatrogenic effects, for example cognitive impairments that co-occur with the residual symptoms of the primary disorder being treated. The observation of comorbid disorders in some cases may reflect diagnostic overlap. Impulsivity, impulsiveness or impulsive behaviour is implicated in a range of diagnostic conditions including substance abuse, affective disorder and obsessive-compulsive disorder. These observations suggest a need to re-evaluate established diagnostic criteria and disorder definitions, focusing instead on symptoms and symptom-profiles