Ebselen has lithium-like effects on central 5-HT2A receptor function.

BACKGROUND AND PURPOSE: Lithium's antidepressant action may be mediated by inhibition of inositol monophosphatase (IMPase), a key enzyme in Gq -protein coupled receptor signalling. Recently, the antioxidant agent ebselen was identified as an IMPase inhibitor. Here, we investigated both ebselen and lithium in models of the 5-HT2A receptor, a Gq -protein coupled receptor involved in lithium's actions. EXPERIMENTAL APPROACH: 5-HT2A receptor function was assessed in mice by measuring the behavioural (head-twitches, ear scratches) and molecular (cortical immediate early gene [IEG] mRNA; Arc, c-fos, Egr2) responses to 5-HT2A receptor agonists. Ebselen and lithium were administered either acutely or repeatedly prior to assessment of 5-HT2A receptor function. Because lithium and 5-HT2A receptor antagonists augment the action of selective serotonin reuptake inhibitors (SSRIs), ebselen was tested for this activity by co-administration with the SSRI citalopram in microdialysis (extracellular 5-HT) experiments. KEY RESULTS: Acute and repeated administration of ebselen inhibited behavioural and IEG responses to the 5-HT2A receptor agonist DOI. Repeated lithium also inhibited DOI-evoked behavioural and IEG responses. In comparison, a selective IMPase inhibitor (L-690330) attenuated the behavioural response to DOI whereas glycogen synthase kinase inhibitor (AR-A014418) did not. Finally, ebselen enhanced the increase in extracellular 5-HT induced by citalopram, and also increased regional brain 5-HT synthesis. CONCLUSIONS AND IMPLICATIONS: Our data demonstrated lithium-mimetic effects of ebselen in different experimental models of 5-HT2A receptor function, probably mediated by IMPase inhibition. This evidence of lithium-like neuropharmacological effects of ebselen adds further support for the clinical testing of ebselen in mood disorders, including as an antidepressant augmenting agent.

Aspects of structural health and condition monitoring of offshore wind turbines.

Wind power has expanded significantly over the past years, although reliability of wind turbine systems, especially of offshore wind turbines, has been many times unsatisfactory in the past. Wind turbine failures are equivalent to crucial financial losses. Therefore, creating and applying strategies that improve the reliability of their components is important for a successful implementation of such systems. Structural health monitoring (SHM) addresses these problems through the monitoring of parameters indicative of the state of the structure examined. Condition monitoring (CM), on the other hand, can be seen as a specialized area of the SHM community that aims at damage detection of, particularly, rotating machinery. The paper is divided into two parts: in the first part, advanced signal processing and machine learning methods are discussed for SHM and CM on wind turbine gearbox and blade damage detection examples. In the second part, an initial exploration of supervisor control and data acquisition systems data of an offshore wind farm is presented, and data-driven approaches are proposed for detecting abnormal behaviour of wind turbines. It is shown that the advanced signal processing methods discussed are effective and that it is important to adopt these SHM strategies in the wind energy sector.

Increase in congenital rubella occurrence after immunisation in Greece: retrospective survey and systematic review.

OBJECTIVE: To describe the events leading to the epidemic of congenital rubella syndrome in Greece in 1993 after a major rubella epidemic. DESIGN: Retrospective survey and systematic review. SETTING: Greece (population 10 million), 1950-95. SUBJECTS: Children, adolescents, and women of childbearing age. RESULTS: Around 1975 in Greece the measles, mumps, and rubella vaccine started being given to boys and girls aged 1 year without policies to attain high vaccination coverage and to protect adolescents and young women. During the 1980s, vaccination coverage for rubella remained consistently below 50%, and the proportion of pregnant women susceptible to rubella gradually increased. In 1993 the incidence of rubella in young adults was higher than in any previous epidemic year. The epidemic of congenital rubella that followed, with 25 serologically confirmed cases (24.6 per 100 000 live births), was probably the largest such epidemic in Greece after 1950. CONCLUSIONS: With low vaccination coverage, the immunisation of boys and girls aged 1 year against rubella carries the theoretical risk of increasing the occurrence of congenital rubella. This phenomenon, which has not been previously reported, occurred in Greece.